[Skin and SARS-CoV-2 in pediatrics].
The clinical presentation, disease course, and outcome of SARS-CoV-2 infection in pediatrics differ from the presentation in adults. In a review by Hoang et al., the prevalence of dermatological manifestations was estimated in 0.25% of a total of 2,445 children with confirmed COVID-19. Similarly, the prevalence of skin manifestations was reported in 3% of 100 children in the Parri's study. A systematic review by Shah et al. analyzed 13 studies with 149 children who met eligibility criteria. The acral erythematous maculopapular lesion was the most common, as well as erythema multiforme, varicella rash, and presentations similar to Kawasaki disease. The duration of the skin lesion was one to two weeks in 43%. Skin biopsy of 18 cases complete superficial and deep perivascular and paracrine lymphocytic infiltrate and lymphocytic vasculitis were reported. RT-PCR was positive in 13.8 % of the cases. The serological markers of herpes simplex virus and parvovirus B19 analyzed were negative, except for Mycoplasma pneumoniae in two of 20 cases. The pathophysiological mechanism of skin lesions secondary to SARS-CoV-2 infection has not yet been explained; likely to be a combination of one or more complex mechanisms, direct skin damages induced by the virus, vasculitis-like reactions either indirect or secondary injuries as a consequence of a systemic inflammatory reaction. Publications from years 2019 to 2021 are reviewed in PubMed as the main search source, using key words.


High-throughput assay using a GFP-expressing replicon for SARS-CoV drug discovery.
The causative agent of severe acute respiratory syndrome (SARS) has been identified as a novel coronavirus, SARS-CoV. The development of rapid screening assays is essential for antiviral drug discovery. By using a cell line expressing a SARS-CoV subgenomic replicon, we developed a high-throughput assay and used it to screen small molecule compounds for inhibitors of SARS-CoV replication in the absence of live virus. The assay system involves minimal manipulation after assay set-up, facilitates automated read-out and minimizes risks associated with hazardous viruses. Based on this assay system, we screened 7035 small molecule compounds from which we identified 7 compounds with anti-SARS-CoV activity. We demonstrate that the compounds inhibited SARS-CoV replication-dependent GFP expression in the replicon cells and reduced SARS-CoV viral protein accumulation and viral RNA copy number in the replicon cells. In a SARS-CoV plaque reduction assay, these compounds were confirmed to have antiviral activity. The target of one of the hit compounds, C12344, was validated by the generation of resistant replicon cells and the identification of the mutations conferring the resistant phenotype. These compounds should be valuable for developing anti-SARS therapeutic drugs as well as research tools to study the mechanism of SARS-CoV replication.


Novel Synthesis of Substituted 2-Trifluoromethyl and 2-Perfluoroalkyl N-Arylpyridinium Compounds-Mechanistic Insights.
We report a new one-pot synthesis of 2-trifluoromethylated/2-perfluoroalkylated N-aryl-substituted pyridiniums, 5,6,7,8-tetrahydroquinoliniums and 6,7,8,9-tetrahydro-5H-cyclohepta[b]-pyridinium compounds starting from an activated β-dicarbonyl analogue (here a perfluoro-alkylated gem-iodoacetoxy derivative), an aromatic amine and a (cyclic or acyclic) ketone. The key step of this multicomponent reaction, involves the formation of a 3-perfluoroalkyl-N,N'-diaryl-1,5-diazapentadiene intermediate, various examples of which were isolated and characterized for the first time, together with investigation of their reactivity. We propose a mechanism involving a concurrent inverse electron demand Diels-Alder or Aza-Robinson cascade cyclisation, followed by a bis-de-anilino-elimination. Noteworthy, a meta-methoxy substituent on the aniline directs the reaction towards a 2-perfluoroalkyl-7-methoxyquinoline, resulting from the direct cyclization of the diazapentadiene intermediate, instead of pyridinium formation. This is the first evidence of synthesis of pyridinium derivatives from activated β-dicarbonyls, ketones, and an aromatic amine, the structures of which (both reactants and products) being analogous to species involved in biological systems, especially upon neurodegenerative diseases such as Parkinson's. Beyond suggesting chemical/biochemical analogies, we thus hope to outline new research directions for understanding the mechanism of in vivo formation of pyridiniums, hence possible pharmaceutical strategies to better monitor, control or prevent it.


Nonaqueous production of nanostructured anatase with high-energy facets.
Although solution-based synthesis is the most powerful and economic method to create nanostructured anatase TiO(2), under those synthesis conditions the {101} facets are the most thermodynamically stable, making it difficult to create anatase nanomaterials with a large percentage of high-energy {001} or {010} facets exposed. Here, we report a facile nonaqueous synthetic route to prepare anatase nanosheets with exposed {001} facets and high-quality rhombic-shaped anatase nanocrystals with a large percentage of exposed {010} facets. Including adscititious water in the nonaqueous synthesis and eliminating the use of carboxylic acid type capping agents are the two keys to integrating the structural diversity from aqueous systems into large-quantity synthesis in nonaqueous systems. The nanostructured TiO(2) that we prepared exhibits conspicuous activity in the photocatalytic degradation of organic contaminants.


Sex difference and socioeconomic inequality of underweight, overweight and obesity among adult population in Bangladesh.
Background: Due to rapid socioeconomic development and epidemiological transition, socioeconomic inequality of underweight, overweight, and obesity are becoming a public health concern in Bangladesh. There is a need for country-specific evidence of nutrition inequalities in Bangladesh. Aim: The aim of the study was to measure socioeconomic inequality and decomposition analysis along with the sex differences in underweight, overweight, and obesity among the adult population. Methods: A secondary data analysis was performed in the Bangladesh Demographic and Health Survey (BDHS) 2017-18, a cross-sectional survey used a multi-stage cluster sampling technique. Sociodemographic variables including age, sex, education, socioeconomic status, marital status, and anthropometric data of height and weight were considered for analysis. Body mass index was used for defining underweight, overweight, and obesity. Concentration index (CI) and decomposition analysis were performed for underweight, overweight, and obesity. Results: The proportion of underweight was 15.0%, overweight (23.0%), and obese (5.0%). Underweight was higher in males, whereas overweight and obesity were higher in females. The CI of underweight was -0.121 (p < 0.001), indicating socioeconomic inequality concentrated on lowering socioeconomic status; living in rural areas contributed 14.2% to this inequality. The CI of overweight and obesity was 0.213 (p < 0.001) and 0.142 (p < 0.001), respectively, indicating that inequalities of overweight and obesity concentrated in higher socioeconomic status; urban residency contributed 14.1% and 18.0% to socioeconomic inequality of overweight and obesity. Conclusion: Underweight remains a significant problem for poor people in rural areas, but overweight and obesity were highly prevalent in the higher socioeconomic status of urban areas. Education level and young age group significantly contribute to the socioeconomic inequality of malnutrition. A more detailed epidemiological study is required to understand the causes of socioeconomic disparities of nutritional status in Bangladesh.


Cell-dependent function of HIV-1 Vif for virus replication (Review).
It has been well established that the Vif protein of human immunodeficiency virus type 1 (HIV-1) acts late in the viral life cycle and increases the infectivity of the progeny virions in a producer cell-dependent manner. The virions produced in the absence of Vif in non-permissive cells (Delta Vif) are defective for a step(s) before and/or during reverse transcription. In this review, the functional and structural analyses of these virions including our new data are summarized.


Iron supplementation in female blood donors deferred by copper sulfate screening.
Female blood donors with low hematocrit levels detected by copper sulfate screening were selected randomly to receive either 75 mg of iron per day, as ferrous gluconate, or a calcium phosphate placebo. Their ferritin, serum iron, total iron-binding capacity, zinc protoporphyrin, and hemoglobin values, as well as their suitability to donate blood, were determined initially (Visit 1) and at four follow-up visits (Visits 2-5). By the second visit, the serum ferritin and iron values of donors receiving iron supplementation differed significantly from those of donors receiving placebo. By the fifth visit, a less marked but significant increase in hemoglobin had occurred in the iron group, but not in the placebo group. At no time was there a significant difference between the groups' suitability to donate blood, with each group donating at almost half of their visits. The authors conclude that iron supplementation at this dose level in deferred female blood donors improves their iron status and hemoglobin levels, but does not significantly increase their suitability to donate blood as compared with the suitability of placebo-treated donors.


Single-Cell Transcriptomes Reveal a Complex Cellular Landscape in the Middle Ear and Differential Capacities for Acute Response to Infection.
Single-cell transcriptomics was used to profile cells of the normal murine middle ear. Clustering analysis of 6770 transcriptomes identified 17 cell clusters corresponding to distinct cell types: five epithelial, three stromal, three lymphocyte, two monocyte, two endothelial, one pericyte and one melanocyte cluster. Within some clusters, cell subtypes were identified. While many corresponded to those cell types known from prior studies, several novel types or subtypes were noted. The results indicate unexpected cellular diversity within the resting middle ear mucosa. The resolution of uncomplicated, acute, otitis media is too rapid for cognate immunity to play a major role. Thus innate immunity is likely responsible for normal recovery from middle ear infection. The need for rapid response to pathogens suggests that innate immune genes may be constitutively expressed by middle ear cells. We therefore assessed expression of innate immune genes across all cell types, to evaluate potential for rapid responses to middle ear infection. Resident monocytes/macrophages expressed the most such genes, including pathogen receptors, cytokines, chemokines and chemokine receptors. Other cell types displayed distinct innate immune gene profiles. Epithelial cells preferentially expressed pathogen receptors, bactericidal peptides and mucins. Stromal and endothelial cells expressed pathogen receptors. Pericytes expressed pro-inflammatory cytokines. Lymphocytes expressed chemokine receptors and antimicrobials. The results suggest that tissue monocytes, including macrophages, are the master regulators of the immediate middle ear response to infection, but that virtually all cell types act in concert to mount a defense against pathogens.


Epistasis for fitness-related quantitative traits in Arabidopsis thaliana grown in the field and in the greenhouse.
The extent to which epistasis contributes to adaptation, population differentiation, and speciation is a long-standing and important problem in evolutionary genetics. Using recombinant inbred (RI) lines of Arabidopsis thaliana grown under natural field conditions, we have examined the genetic architecture of fitness-correlated traits with respect to epistasis; we identified both single-locus additive and two-locus epistatic QTL for natural variation in fruit number, germination, and seed length and width. For fruit number, we found seven significant epistatic interactions, but only two additive QTL. For seed germination, length, and width, there were from two to four additive QTL and from five to eight epistatic interactions. The epistatic interactions were both positive and negative. In each case, the magnitude of the epistatic effects was roughly double that of the effects of the additive QTL, varying from -41% to +29% for fruit number and from -5% to +4% for seed germination, length, and width. A number of the QTL that we describe participate in more than one epistatic interaction, and some loci identified as additive also may participate in an epistatic interaction; the genetic architecture for fitness traits may be a network of additive and epistatic effects. We compared the map positions of the additive and epistatic QTL for germination, seed width, and seed length from plants grown in both the field and the greenhouse. While the total number of significant additive and epistatic QTL was similar under the two growth conditions, the map locations were largely different. We found a small number of significant epistatic QTL x environment effects when we tested directly for them. Our results support the idea that epistatic interactions are an important part of natural genetic variation and reinforce the need for caution in comparing results from greenhouse-grown and field-grown plants.


Connexons and pannexons: newcomers in neurophysiology.
Connexin hemichannels are single membrane channels which have been traditionally thought to work in pairs to form gap junction channels across two opposing cells. In astrocytes, gap junction channels allow direct intercellular communication and greatly facilitate the transmission of signals. Recently, there has been growing evidence demonstrating that connexin hemichannels, as well as pannexin channels, on their own are open in various conditions. They allow bidirectional flow of ions and signaling molecules and act as release sites for transmitters like ATP and glutamate into the extracellular space. While much attention has focused on the function of connexin hemichannels and pannexons during pathological situations like epilepsy, inflammation, neurodegeneration or ischemia, their potential roles in physiology is often ignored. In order to fully understand the dynamic properties and roles of connexin hemichannels and pannexons in the brain, it is essential to decipher whether they also have some physiological functions and contribute to normal cerebral processes. Here, we present recent studies in the CNS suggesting emerging physiological functions of connexin hemichannels and pannexons in normal neuronal activity and behavior. We also discuss how these pioneer studies pave the way for future research to extend the physiological relevance of connexons and pannexons, and some fundamental issues yet to be addressed.


Frontline Hyper-CVAD Plus Venetoclax for Pediatric Blastic Plasmacytoid Dendritic Cell Neoplasm.
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy, especially in pediatrics, that can involve the bone marrow, skin, lymph nodes, and central nervous system (CNS). Given its variable clinical presentation, coupled with an immunohistochemistry pattern (CD4, CD56, TCF4, TCL-1, and CD123 positivity) that differs from other myeloid neoplasms, the diagnosis of BPDCN can be missed. Limited data are available to guide the treatment of pediatric BPDCN. Herein, we report a case of a pediatric patient who had BPDCN with central nervous system, orbital, and skin involvement. This patient achieved complete remission after receiving modified hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone with venetoclax and intrathecal chemotherapy. He remains disease-free 200 days after receiving a stem cell transplant. This represents the first known published pediatric case using a modified hyper-CVAD plus venetoclax regimen for treating a pediatric BPDCN patient in the frontline setting.


Regulation of specialized metabolism by WRKY transcription factors.
WRKY transcription factors (TFs) are well known for regulating plant abiotic and biotic stress tolerance. However, much less is known about how WRKY TFs affect plant-specialized metabolism. Analysis of WRKY TFs regulating the production of specialized metabolites emphasizes the values of the family outside of traditionally accepted roles in stress tolerance. WRKYs with conserved roles across plant species seem to be essential in regulating specialized metabolism. Overall, the WRKY family plays an essential role in regulating the biosynthesis of important pharmaceutical, aromatherapy, biofuel, and industrial components, warranting considerable attention in the forthcoming years.


Determination of ribonuclease H surface enzyme kinetics by surface plasmon resonance imaging and surface plasmon fluorescence spectroscopy.
The kinetics of the ribonuclease H (RNase H) surface hydrolysis of RNA-DNA heteroduplexes formed on DNA microarrays was studied using a combination of real-time surface plasmon resonance imaging (SPRI) and surface plasmon fluorescence spectroscopy (SPFS). Time-dependent SPRI and SPFS data at various enzyme concentrations were quantitatively analyzed using a simple model that couples diffusion, enzyme adsorption, and surface enzyme kinetics. This model is characterized by a set of three rate constants, enzyme adsorption (k(a)), enzyme desorption (k(d)), enzyme catalysis (k(cat)), and one dimensionless diffusion parameter (beta). Values of k(a) = 3.15 (+/-0.20) x 10(6) M(-1).s(-1), k(d) = 0.10 (+/-0.05) s(-1), and k(cat) = 0.95 (+/-0.10) s(-1) were determined from fitting all of the SPRI and SPFS data sets. One of the most interesting kinetic parameters is the surface RNase H hydrolysis reaction rate constant (k(cat)), which was found to be approximately 10 times slower than that observed in solution, but approximately 100 times faster than that recently observed for the exonuclease III surface hydrolysis of double-stranded DNA microarrays (k(cat) = 0.009 s(-1)). Moreover, the surface coverage of the intermediate enzyme-substrate complex (ES) was found to be extremely small during the course of the reaction because k(cat) is much larger than the product of k(a) and the bulk enzyme concentration.


A Motivational Interviewing Chatbot With Generative Reflections for Increasing Readiness to Quit Smoking: Iterative Development Study.
The motivational interviewing (MI) approach has been shown to help move ambivalent smokers toward the decision to quit smoking. There have been several attempts to broaden access to MI through text-based chatbots. These typically use scripted responses to client statements, but such nonspecific responses have been shown to reduce effectiveness. Recent advances in natural language processing provide a new way to create responses that are specific to a client's statements, using a generative language model. This study aimed to design, evolve, and measure the effectiveness of a chatbot system that can guide ambivalent people who smoke toward the decision to quit smoking with MI-style generative reflections. Over time, 4 different MI chatbot versions were evolved, and each version was tested with a separate group of ambivalent smokers. A total of 349 smokers were recruited through a web-based recruitment platform. The first chatbot version only asked questions without reflections on the answers. The second version asked the questions and provided reflections with an initial version of the reflection generator. The third version used an improved reflection generator, and the fourth version added extended interaction on some of the questions. Participants' readiness to quit was measured before the conversation and 1 week later using an 11-point scale that measured 3 attributes related to smoking cessation: readiness, confidence, and importance. The number of quit attempts made in the week before the conversation and the week after was surveyed; in addition, participants rated the perceived empathy of the chatbot. The main body of the conversation consists of 5 scripted questions, responses from participants, and (for 3 of the 4 versions) generated reflections. A pretrained transformer-based neural network was fine-tuned on examples of high-quality reflections to generate MI reflections. The increase in average confidence using the nongenerative version was 1.0 (SD 2.0; P=.001), whereas for the 3 generative versions, the increases ranged from 1.2 to 1.3 (SD 2.0-2.3; P<.001). The extended conversation with improved generative reflections was the only version associated with a significant increase in average importance (0.7, SD 2.0; P<.001) and readiness (0.4, SD 1.7; P=.01). The enhanced reflection and extended conversations exhibited significantly better perceived empathy than the nongenerative conversation (P=.02 and P=.004, respectively). The number of quit attempts did not significantly change between the week before the conversation and the week after across all 4 conversations. The results suggest that generative reflections increase the impact of a conversation on readiness to quit smoking 1 week later, although a significant portion of the impact seen so far can be achieved by only asking questions without the reflections. These results support further evolution of the chatbot conversation and can serve as a basis for comparison against more advanced versions.


Four m6A RNA Methylation Gene Signatures and Their Prognostic Values in Lung Adenocarcinoma.
Introduction: Evidence demonstrates that N6-methyladenosine (m6A) modification plays an increasingly important role in the development of tumors. The aim of this study is to explore the expression of m6A-related regulators in lung adenocarcinoma, identify the effect of altered key factors modified by m6A on the prognosis of patients with lung adenocarcinoma. Methods: A comprehensive analysis of m6A-related gene expressions in patients with lung adenocarcinoma based on The Cancer Genome Atlas database (TCGA) and the CBioPortal database. A prognostic risk score was established based on a linear combination of 4 key gene expression levels using the regression coefficients of the multivariate Cox regression models. Immunohistochemical staining analysis was performed to validate the relationship between the protein expression level of m6A regulators and the prognosis of patients retrospectively. The possible mechanism and prospective therapeutic targets of these key m6A molecules were explored by the M6A2Target database and the CMAP database. Results: Mutation pattern analysis revealed that 32% of 656 patients had genetic alterations. Four genes (writer: methyltransferase like 3 [METTL3] and three readers: insulin like growth factor 2 mRNA binding protein 2 [IGF2BP2], heterogeneous nuclear ribonucleoprotein C [HNRNPC], and heterogeneous nuclear ribonucleoprotein A2/B1 [HNRNPA2B1]) were selected to construct a survival risk prediction model and the results of immunohistochemical staining showed that the expression of these four m6A genes was significantly different between lung adenocarcinoma tissues and normal lung tissues (p < .01). The possible downstream genes and prospective therapeutic targets of these four m6A key molecules were discovered. Conclusion: These four m6A RNA methylation regulators may be effective prognostic and diagnostic factors which can provide auxiliary diagnosis and prognosis of lung adenocarcinoma.


Avoidable errors in dealing with anaphylactoid reactions to iodinated contrast media.
Contrast reactions are much less common today than in the past. This is principally because of the current and predominant use of low and iso-osmolar contrast media compared with the prior use of high osmolality contrast media. As a result of the significantly diminished frequency, there are now fewer opportunities for physicians to recognize and appropriately treat such adverse reactions. In review of the literature combined with our own clinical and legal experience, 12 potential errors were identified and these are reviewed in detail so that they can be avoided by the physician-in-charge. Basic treatment considerations are presented along with a plan to systematize an approach to contrast reactions, simplify treatment options and plans, and schedule periodic drills.


Immunoregulatory activity in adult rat testicular interstitial fluid: relationship with intratesticular CD8+ lymphocytes following treatment with ethane dimethane sulfonate and testosterone implants.
Regulation of T-cell traffic and function in the adult rat testis was assessed following treatment with the specific Leydig cell cytoxin, ethane dimethane sulfonate (EDS), and s.c. testosterone implants to prevent Leydig cell recovery. The distribution of T-cell subsets in the testis was determined immunohistochemically using stereological techniques. Testicular T cell-inhibiting activity in the interstitial fluid was measured using a phytohemagglutinin-activated rat thymocyte proliferation bioassay. The mostly cytotoxic CD8+ T-cell subset predominated over the CD4+ (regulatory) T-cell subset in the normal rat testis. Destruction of the Leydig cells caused a rapid preferential increase in testicular CD4+ T cells, which was followed by an increase in both the CD8+ subset and T cell-inhibiting activity in the Leydig cell-deficient testis. After Leydig cell recovery, there was a significant shift toward the CD8+ T-cell subset in the EDS-treated testis but not in the EDS-treated/testosterone-implanted testis. Total T-cell numbers and inhibitory activity in the testis returned to control levels regardless of whether the Leydig cells were allowed to recover. The level of inhibitory activity was closely related to the number of CD8+ T cells in the testis across all experimental groups, but it showed no relationship with pituitary hormones, macrophage numbers, or intratesticular testosterone levels. The data suggest that 1) cytotoxic lymphocytes have a potentially significant role in testicular function and 2) T cell-inhibiting activity in the testis interstitium is not substantially affected by changes in pituitary hormones or Leydig cell function, but appears to be related to local changes in immune activity.


Spatial Distribution and Health Risk Assessment of Soil Pollution by Heavy Metals in Ijebu-Ode, Nigeria.
Soil pollution by heavy metals in urban areas is of major concern to city planners and policy makers because of the potential threat to human health. Hence, an investigation of soil pollution is crucial to urban environmental assessment and management. To determine the spatial distribution and health risk assessment of seven heavy metals (cadmium (Cd), chromium (Cr), copper (Cu), manganese (Mn), nickel (Ni), lead (Pb), and zinc (Zn)) around Ijebu-ode, southwest Nigeria. Surface soil samples were analyzed for Cd, Cr, Cu, Mn, Ni, Pb, and Zn levels using standard procedures. Geographic information system (GIS) data, pollution indices (enrichment factor, geo-accumulation index), and the health risk assessment model, respectively, were used to analyze the spatial distribution, pollution level, and potential health risk of heavy metals. Low pH was observed in the urban soils. The average concentrations of the seven heavy metals investigated were in order of Zn > Pb > Mn > Cu > Cd > Ni > Cr. There was high spatial variation in the distribution patterns of the heavy metals. The cancer risks for Cu, Mn, Pb, and Zn for children (1.50 × 10-3 - 2.71 × 10-2) and Mn, Pb, and Zn for adults (7.89 × 10-4 - 2.97 × 10-3) were higher than the acceptable range of 1 × 10-6 - 1 × 10-4. Anthropogenic activities from different urban land uses contribute to the pollution levels and spatial distribution of heavy metals in soils. Increasing pollution of urban soil may contribute to the occurrence of some health risk for residents in the study area. The authors declare no competing financial interests.


Regulation of sulfur assimilation pathways in Burkholderia cenocepacia: identification of transcription factors CysB and SsuR and their role in control of target genes.
Two genes encoding transcriptional regulators involved in sulfur assimilation pathways in Burkholderia cenocepacia strain 715j have been identified and characterized functionally. Knockout mutations in each of the B. cenocepacia genes were constructed and introduced into the genome of 715j by allelic replacement. Studies on the utilization of various sulfur sources by 715j and the obtained mutants demonstrated that one of the B. cenocepacia regulators, designated CysB, is preferentially involved in the control of sulfate transport and reduction, while the other, designated SsuR, is required for aliphatic sulfonate utilization. Using transcriptional promoter-lacZ fusions and DNA-binding experiments, we identified several target promoters for positive control by CysB and/or SsuR--sbpp (preceding the sbp cysT cysW cysA ssuR cluster), cysIp (preceding the cysI cysD1 cysN cysH cysG cluster), cysD2p (preceding a separate cluster, cysD2 cysNC), and ssuDp (located upstream of the ssuDCB operon)--and we demonstrated overlapping functions of CysB and SsuR at particular promoters. We also demonstrated that the cysB gene is negatively controlled by both CysB and SsuR but the ssuR gene itself is not significantly regulated as a separate transcription unit. The function of B. cenocepacia CysB (in vivo and in vitro) appeared to be independent of the presence of acetylserine, the indispensable coinducer of the CysB regulators of Escherichia coli and Salmonella. The phylogenetic relationships among members of the "CysB family" in the gamma and beta subphyla are presented.


Neurofibromatosis: an update of ophthalmic characteristics and applications of optical coherence tomography.
Neurofibromatosis (NF) is a multisystem disorder and tumor predisposition syndrome caused by genetic mutation on chromosome 17-17q11.2 in NF type 1 (NF1), and on chromosome 22-22q12.2 in NF type 2. The disorder is characterized by considerable heterogeneity of clinical expression. NF1 is the form with the most characteristic ocular manifestations. Lisch nodules of the iris are among the well-known diagnostic criteria for the disease. Glaucoma and associated globe enlargement have been described in a significant proportion of patients with NF1 and orbital-facial involvement. Optic nerve glioma may cause strabismus and proptosis, and palpebral neurofibroma may reach considerable size and occasionally show malignant transformation. Near infrared reflectance has greatly contributed to enhancing our knowledge on choroidal alterations in NF1. Indeed, some authors have proposed to include these among the diagnostic criteria. Optical coherence tomography has given new insight on retinal alterations and is a noninvasive tool in the management of optic nerve gliomas in children. Ocular manifestations in NF type 2 can range from early-onset cataracts in up to 80% of cases to optic nerve hamartomas and combined pigment epithelial and retinal hamartomas.


Saccadic eye movement analysis as a measure of drug effects on human psychomotor performance.
Analysis of human horizontal saccadic eye movements can provide measurements of central nervous system depression and stimulation. Effects on saccadic eye movements have been observed in normal volunteers with barbiturates, benzodiazepines, opiates and related compounds, carbamazepine, amphetamine and ethanol. A suite of programmes have been developed to allow the generation, collection and analysis of saccadic eye movements using a CBM 3032, 8032 or BBC B microcomputer. The system allows almost continuous sampling and rapid analysis of movements.


An Energy-Efficient Algorithm for Wearable Electrocardiogram Signal Processing in Ubiquitous Healthcare Applications.
Rapid progress and emerging trends in miniaturized medical devices have enabled the un-obtrusive monitoring of physiological signals and daily activities of everyone's life in a prominent and pervasive manner. Due to the power-constrained nature of conventional wearable sensor devices during ubiquitous sensing (US), energy-efficiency has become one of the highly demanding and debatable issues in healthcare. This paper develops a single chip-based wearable wireless electrocardiogram (ECG) monitoring system by adopting analog front end (AFE) chip model ADS1292R from Texas Instruments. The developed chip collects real-time ECG data with two adopted channels for continuous monitoring of human heart activity. Then, these two channels and the AFE are built into a right leg drive right leg drive (RLD) driver circuit with lead-off detection and medical graded test signal. Human ECG data was collected at 60 beats per minute (BPM) to 120 BPM with 60 Hz noise and considered throughout the experimental set-up. Moreover, notch filter (cutoff frequency 60 Hz), high-pass filter (cutoff frequency 0.67 Hz), and low-pass filter (cutoff frequency 100 Hz) with cut-off frequencies of 60 Hz, 0.67 Hz, and 100 Hz, respectively, were designed with bilinear transformation for rectifying the power-line noise and artifacts while extracting real-time ECG signals. Finally, a transmission power control-based energy-efficient (ETPC) algorithm is proposed, implemented on the hardware and then compared with the several conventional TPC methods. Experimental results reveal that our developed chip collects real-time ECG data efficiently, and the proposed ETPC algorithm achieves higher energy savings of 35.5% with a slightly larger packet loss ratio (PLR) as compared to conventional TPC (e.g., constant TPC, Gao's, and Xiao's methods).


[Reliability evaluation for thirteen parameters describing anteroposterior apical base relationship in Angle Class II division 1 patients].
To study 13 different cephalometric measurements of the anteroposterior jaw relationship in Angle Class II division 1 statistically and geometrically, and to discuss the effects of various factors on this relationship, and then to choose the most adequate measurements. 120 patients with skeletal malocclusion Angle Class II division 1 were selected. The samples consisted of 60 men and 60 women between 20 to 28 years of age. Lateral cephalometric radiograph for each patient was taken in natural head posture by the same operator. A wire plumb line and suspended weight recorded the true vertical on each radiograph. The subject was then asked to determine the self-balanced position of the head. After determining the self-balanced neutral position, the subject was asked to look into his/her own eyes in the mirror. ANB angle, A-B plane angle, Wits appraisal, AF-BF distance, AXB angle, AB/SN4 distance, AB/PP distance, AXD angle, AD/SN distance, SGn/AB angle, APDI, FABA angle, beta angle and AB/HP distance were measured. Coefficient correlations among measurements were tabulated to determine which combination would produce a higher value. Fuzzy grouping analysis was made. Statistically significant and highly correlated relationships was found among many measurements except Wits appraisal and SGn/AB angle. The thirteen measurements could be divided into five clusters. The cephalometric measurements except Wits appraisal and SGn/AB angle can be used to evaluate anteroposterior jaw relationship. The AB/SN4 distance is the most adequate measurements. ANB angle, A-B plane angle, AF-BF distance, AXB angle, AB/PP distance, APDI, FABA angle and beta angle are similar in describing anteroposterior apical base relationship in Angle Class II division 1 patients.


Using notifications data to increase hepatitis C testing and treatment rates in Queensland.
Australia's goal of eliminating hepatitis C by 2030 requires increases in uptake of and access to testing and treatment. As hepatitis C is a notifiable condition, health departments have access to information about people exposed to the hepatitis C virus (HCV), including the details of notifying clinicians who ordered their diagnostic pathology tests. Hepatitis C RNA testing confirms active infection that requires treatment, whereas a positive antibody test result only indicates prior exposure to the virus. We undertook a pilot project in Queensland to follow up hepatitis C notifications with clinicians, aiming to increase HCV-RNA testing and treatment uptake. For all individuals with a first-time hepatitis C notification in Queensland between 3 November 2020 and 28 May 2021, we sought information regarding hepatitis C RNA testing from laboratories, excluding those cases diagnosed in prisons. Cases who did not have RNA testing identified as part of or after their initial diagnostic tests were followed up via their notifying clinician. Interviews with selected clinicians were undertaken to improve our understanding of the follow-up process. There were 769 new hepatitis C notifications during our study period: 244 had no subsequent RNA test identified and were followed up for this study. Of these, 134 cases were lost to follow-up; 26 were already being effectively case managed; 22 reported previous treatment and no further risk; and 62 were eligible for HCV-RNA testing. Twenty-six cases subsequently started hepatitis C treatment. Thirty-four percent of notifications that required follow-up resulted from testing initially requested in hospital settings. Following up hepatitis C notifications can result in increased treatment rates; however, the process was resource-intensive and often failed to result in further contact between clinicians and patients. Our findings also highlight the importance of supporting better continuity of care between hospitals and community settings.


Phase-amplitude coupling and interlaminar synchrony are correlated in human neocortex.
One of the striking manifestations of neuronal population activity is that of rhythmic oscillations in the local field potential. It is thought that such oscillatory patterns, including phase-amplitude coupling (PAC) and inter-regional synchrony, may represent forms of local and long-range cortical computations, respectively. Although it has been speculated that these two oscillatory patterns are functionally related, and bind disparate cortical assemblies to one another at different timescales, there is little direct evidence to support this hypothesis. We have demonstrated recently that theta to high-gamma PAC and interlaminar phase coherence at theta frequencies can be generated in human cortical slices maintained in vitro. Here we show that not only do such oscillatory patterns exist within human temporal neocortex, but that the strength of one is related to the strength of the other. We demonstrate that at theta frequencies, metrics of temporal synchrony between superficial and deep cortical laminae (phase-dependent power correlations, and phase coherence) are correlated to the magnitude of intralaminar PAC between theta and high-gamma. Specifically, our results suggest that interlaminar communication within human temporal neocortex and local laminar excitability are linked to one another through a dependence mediated by theta oscillations. More generally, our results provide evidence for the hypothesis that theta oscillations may coordinate inter-areal excitability in the human brain.


An ELISA for IgA, IgG and IgM-RF measurement. I. Parameters of the assay.
A simple and rapid solid phase ELISA for the stepless determination of IgA, IgG and IgM-RF was developed. The ELISA works with Fc parts of human IgG as antigen. Specificity, validity and precision were tested. RF complex dissociation by urea and separation by gel filtration was performed in several samples to obtain information of the transfer of non-RF-IgG by pentameric IgM-RF. The RF-ELISA may give better information on the significance of RF of the three Ig classes in the clinical course of RA.


Coronavirus Disease 2019 Hangover: A Rising Tide of Alcohol Use Disorder and Alcohol-Associated Liver Disease.
The coronavirus disease 2019 (COVID-19) pandemic has had a tremendous global impact since it began in November of 2019. However, there are concerns that the COVID-19 pandemic will not affect all equally and that some populations will be particularly vulnerable. Relevant to liver disease, patients with alcohol use disorder (AUD) and alcohol-associated liver disease (ALD) may be among the populations that are the most severely impacted. The reasons for this include being at a higher risk of severe COVID-19 infection due to a depressed immune system and high-risk underlying comorbidities, the injurious effect of COVID-19 on the liver, the inability to attend regular visits with providers, diversion of hospital resources, and social isolation leading to psychological decompensation and increased drinking or relapse. As a result, we fear that there will be a dramatic rising tide of alcohol relapse, admissions for decompensated ALD, and an increase in newly diagnosed patients with AUD/ALD post-COVID-19 pandemic. Providers and their institutions should implement preemptive strategies such as telehealth and aggressive patient outreach programs now to curb this anticipated problem. Liver transplantation (LT) centers should adapt to the pandemic by considering leniency to some LT candidates with ALD who cannot access appropriate alcohol treatment due to the current situation. In conclusion, the COVID-19 pandemic will likely be especially detrimental to patients with AUD/ALD, and actions need to be taken now to limit the scope of this anticipated problem.


[Psychoeducational Group Interventions for Families with Parental Cancer].
Psychoeducational Group Interventions for Families with Parental Cancer Parental cancer constitutes a risk factor for the psychological development of all family members. Studies show that children as well as parents suffer losses in their quality of life and their psychological well-being and that participation in a psychological intervention results in an improvement of these parameters. This study examines two group interventions (children group for children with parents suffering from cancer; parental seminar for cancer patients and their partners) in comparison to a waiting group. The target parameters quality of life and psychological well-being of the three groups are compared on the basis of a variance analysis with repeated measurements with three measurement dates (pre, post and follow-up) and the intensity of effects (eta2) is being determined. Participants of the intervention groups show significant improvements in their values. The individual direct participants of the groups (children, parents) benefit most markedly from the interventions but also the other, non-participating family members show improvements in their parameters. The results also show that restrictions in the quality of life of the parents and children are not being reduced by themselves over time without intervention but remain evenly on a low level or are even being declined. Therefore, it is advisable to offer intervention to families with a parent suffering from cancer.


[The effect of inhaled anticholinergic drugs (tiotropium bromide) on asthma patients with persistent obstructive ventilatory impairment].
This study investigated the effects of tiotropium bromide on chronic asthma patients with persistent obstructive ventilatory impairment (FEV1/FVC%<70%) like COPD. Twenty-four patients (14 males, 10 females, mean age 64.3±10.7 years old) were enrolled. They were all treated with a high dose inhaled steroids and a long-acting β2-agonist. All patients had bronchial reversibility, normal diffusing capacity (DLCO) and no low attenuation areas in HRCT. This study examined the FEV1 at baseline and after inhalation of short-acting bronchodilators (400 μg salbutamol and 40 μg ipratropium, 15 minutes and 30 minutes after, respectively). Eleven patients agreed to take an additional treatment with tiotropium, and received 18 μg of tiotropium per daily for one year. The usual treatments were continued for 7 patients that did not agree to take tiotropium and for 6 patients who were ineligible for tiotropium due to co-morbidities. The FVC, FEV1, FEV1/FVC%, V50, and IC were compared between the two groups after one year. FEV1 and V50 were significantly elevated after one year in the tiotropium-treated patients in comparison to those in the 13 subjects that did not receive tiotropium bromide, after adjusting for age, smoking and the values determined on enrollment. There was a positive correlation between the change of FEV1 30 min after ipratropium inhalation (short-term effect) and FEV1 one year after tiotropium inhalation (long-term effect). Combination treatment with tiotropium, high dose steroids and long-acting β2 agonist inhalation provides improvement in the expiratory flow limitations of asthma patients with persistent obstructive ventilatory impairment.


Rotational Modulation of Ã2A″-State Photodissociation of HCO via Renner-Teller Nonadiabatic Transitions.
By examining the product-state distribution of a prototypical nonadiabatic predissociation system, HCO(Ã2A″-X̃2A'), we demonstrate that the dissociation dynamics is strongly modulated by parent rotational quantum numbers. The predissociation of the nominal (νC-H = 0, νbend, νC-O = 1) vibronic levels of the Ã2A″ state surprisingly gives rise to both vibrational ground and excited states of the CO product, despite the assumed spectator nature of the CO moiety. This anomaly is attributed to the dependence of the lifetime of the vibronic resonance facilitated by the Renner-Teller interaction on the parent rotational angular momentum quantum numbers coupled with transient intensity borrowing from nearby vibronic resonances with νC-O = 0. This unique phenomenon is a purely quantum mechanical behavior that has no classical analogue.


Heyde Syndrome Complicated by Essential Thrombocythemia: A Case Report.
Heyde syndrome is a multisystem disorder characterized by the triad of aortic stenosis (AS), gastrointestinal bleeding, and acquired von Willebrand syndrome. Age-related degeneration is the most common cause of aortic stenosis and is frequently encountered in today's aging society. Approximately 20% of patients with severe aortic stenosis have Heyde syndrome. We encountered an older patient with primary thrombocytosis who was brought to a rural community hospital with bloody stools and was diagnosed with bleeding from an intestinal arteriovenous malformation. A final diagnosis of Heyde syndrome was made based on the presence of severe aortic stenosis and the presence of schistocytes in peripheral blood smears. Valvular diseases can complicate chronic hematological diseases. When the rapid progression of anemia and segmented red blood cells in the peripheral blood are observed in patients with severe aortic stenosis, Heyde syndrome should be considered based on peripheral blood smears and clinical course.


Molecular-dynamics simulation of the effect of ions on a liquid-liquid interface for a partially miscible mixture.
Molecular-dynamics simulations were performed to model the effect of added salt ions on the liquid-liquid interface in a partially miscible system. Simulations of the interface between saturated phases of a model 1-hexanol+water system show a bilayer structure of 1-hexanol molecules at the interface with -OH heads of the first layer directed into the water phase and the opposite orientation for the second layer. The alignment of the polar -OH groups at the interface stabilizes a charge separation of sodium and chloride ions when salt is introduced into the aqueous phase, producing an electrical double layer. Chloride ions aggregate nearer the interface and sodium ions move toward the bulk water phase, consistent with the explanation that the -OH alignment presents a region of partial positive charges to which the hydrated chloride atoms are attracted. Ions near the interface were found to be less solvated than those in the bulk phase. An electric field was also applied to drive ions through the interface. Ions crossing the interface tended to shed water molecules as they entered the hexanol bilayer, leaving a trail of water molecules. Stabilization and facilitated transport of the ion by interactions with the second layer of hexanol molecules appeared to be an important step in the mechanism of sodium ion transport.


Reduced soil fauna decomposition in a high background radiation area.
Decomposition of litter and organic matter is a very important soil ecosystem function where soil fauna play an important role. Knowledge of the responses in decomposition and soil fauna to different stressors is therefore crucial. However, the extent to which radioactivity may affect soil fauna is not so well known. There are some results showing effects on soil fauna at uranium mines and near Chernobyl from relatively high levels of anthropogenic radionuclides. We hypothesize that naturally occurring radionuclides affect soil fauna and thus litter decomposition, which will covary with radionuclide levels when accounting for important soil parameters. We have therefore used standardised litterbags with two different mesh sizes filled with birch leaves (Betula pubescens) to assess litter decomposition in an area with enhanced levels of naturally occurring radionuclides in the thorium (232Th) and uranium (238U) decay chains while controlling for variation in important soil parameters like pH, organic matter content, moisture and large grain size. We show that decomposition rate is higher in litterbags with large mesh size compared to litterbags with a fine mesh size that excludes soil fauna. We also find that litter dried at room temperature is decomposed at a faster rate than litter dried in oven (60⁰C). This was surprising given the associated denaturation of proteins and anticipated increased nutritional level but may be explained by the increased stiffness of oven-dried litter. This result is important since different studies often use either oven-dried or room temperature-dried litter. Taking the above into account, we explore statistical models to show large and expected effects of soil parameters but also significant effects on litter decomposition of the naturally occurring radionuclide levels. We use the ERICA tool to estimate total dose rate per coarse litterbag for four different model organisms, and in subsequent different statistical models we identify that the model including the dose rates of a small tube-shape is the best statistical model. In another statistical model including soil parameters and radionuclide distributions, 226Ra (or uranium precursory radionuclides) explain variation in litter decomposition while 228Ra (and precursors) do not. This may hint to chemical toxicity effects of uranium. However, when combining this model with the best model, the resulting simplified model is equal to the tube-shape dose-rate model. There is thus a need for more research on how naturally occurring radionuclides affect soil fauna, but the study at hand show the importance of an ecosystem approach and the ecosystem parameter soil decomposition.


Chemical composition and anti-inflammatory activity of the leaves of Byrsonima verbascifolia.
An ethnopharmacological survey indicates that the genus Byrsonima has some medicinal species that are commonly found in the Brazilian Cerrado and has been used as an anti-inflammatory and for gastroduodenal disorders. The aim of this study was to evaluate the anti-inflammatory and antioxidant activity along with qualitative chemical characterization of the methanolic extract of the leaves of Byrsonima verbascifolia (BvME) obtained by exhaustive percolation. The data from the chemical analyses by liquid chromatography-mass spectrometry led to tentative identification of 42 compounds belonging to proanthocyanidins, galloyl quinic acid derivatives, flavonoids, and triterpene glycoside derivatives. BvME contain flavonoids and show an antioxidative activity. The methanolic extract administered intraperitoneally at doses of 50, 100, or 300 mg/kg showed a significant reduction in paw edema and modulated the neutrophil influx in a mouse model. Furthermore, the anti-edematogenic activity of the extract provided in smaller doses (12.5 and 25 mg/kg) was also demonstrated in a mouse paw edema model. The extract inhibited NO production by macrophages induced by lipopolysaccharide. We presume that the anti-inflammatory effects of BvME are due to a combination of compounds present in B. verbascifolia, including catechins (procyanidins), flavonoids, and triterpene glycosides and that these anti-inflammatory actions should be mediated, at least partly, through the inhibition of NO production. This study supports and validates the ethnopharmacological uses of B. verbascifolia as an anti-inflammatory.


A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike.
A major challenge in understanding SARS-CoV-2 evolution is interpreting the antigenic and functional effects of emerging mutations in the viral spike protein. Here we describe a new deep mutational scanning platform based on non-replicative pseudotyped lentiviruses that directly quantifies how large numbers of spike mutations impact antibody neutralization and pseudovirus infection. We demonstrate this new platform by making libraries of the Omicron BA.1 and Delta spikes. These libraries each contain ~7000 distinct amino-acid mutations in the context of up to ~135,000 unique mutation combinations. We use these libraries to map escape mutations from neutralizing antibodies targeting the receptor binding domain, N-terminal domain, and S2 subunit of spike. Overall, this work establishes a high-throughput and safe approach to measure how ~10 5 combinations of mutations affect antibody neutralization and spike-mediated infection. Notably, the platform described here can be extended to the entry proteins of many other viruses.


Initial computed tomography imaging details during first-line systemic therapy is of significant prognostic value in patients with naïve, unresectable metastatic renal cell carcinoma.
We aimed to determine the prognostic significance of computed tomography imaging parameters of unresectable primary renal tumor lesions, obtained at baseline and at first follow-up, on overall survival in naïve, unresectable metastatic renal cell carcinoma patients during first-line systemic therapy. Clinicopathological parameters of 56 patients treated between 2007 and 2015, including imaging parameters (such as the longest tumor diameter, necrotic area diameter, and attenuation in primary renal tumor lesions on baseline vs. follow-up computed tomography), were retrospectively reviewed to derive predictive factors of overall survival. The best overall response was measured according to the RECIST v1.1. The median treatment period was 206.3 days and the median follow-up was 14.6 months. Forty-four (78.6%) patients progressed after a median 4.6 months of progression-free survival, and 6 (10.7%) patients survived with a median overall survival of 12.5 months. Multivariate analysis showed that the baseline tumor diameter (hazard ratio [HR] 0.903) and mean attenuation (HR 0.936), change of tumor diameter (HR 0.714) and necrosis diameter (HR 0.861), change in the percentage of tumor diameter (HR 1.483) and of necrosis diameter (HR 1.028) between baseline and follow-up computed tomography images; treatment duration (HR 0.986) and baseline serum hemoglobin (HR 1.790) and albumin level (HR 0.060) were significant factors for overall survival (p<0.05). The study showed that baseline and first follow-up computed tomography findings of primary renal lesions during first-line systemic therapy are useful and significant predictors of OS in patients with naïve unresectable mRCC.


The utility of albuterol nebulized with heliox during acute asthma exacerbations.
Heliox improves lung deposition of inhaled particles when compared with air or oxygen inhalation. We studied the spirometric effects of albuterol nebulized with heliox during emergency room visits for asthma exacerbations. Forty-five patients were randomized to receive albuterol nebulized with oxygen (control) versus heliox (n = 22 control and 23 heliox subjects). At baseline, demographics, outpatient asthma medications, vital signs, oxygen saturation, and forced expiratory volume in one second were not different between the two groups. Three consecutive albuterol treatments were given to each group. The heliox group had a significantly higher heart rate after albuterol nebulization compared with the control group. Following albuterol Treatment 1, the median change in forced expiratory volume in one second was 14.6% in the control group and 32.4% in the heliox group (p = 0.007). After Treatment 2, the results were 22.7% versus 51.5%, respectively (p = 0.007). After Treatment 3, the results were 26.6% versus 65.1%, respectively (p = 0.016). We conclude that during acute asthma exacerbations, albuterol nebulized with heliox leads to a more significant improvement in spirometry when compared with albuterol nebulized with oxygen. This is likely due to the low-density gas improving albuterol deposition in the distal airways.


Management and outcomes of Burkholderia cepacia complex bacteremia in patients without cystic fibrosis: a retrospective observational study.
Burkholderia cepacia complex (BCC) is an emerging pathogen of nosocomial infection in chronic or critically ill patients without cystic fibrosis (CF). The objective was to evaluate the management and outcomes of BCC bacteremia in patients without CF. We conducted a retrospective study of non-CF adult patients with BCC bacteremia between January 1997 and December 2016 at 4 tertiary hospitals in South Korea. A total of 216 non-CF patients with BCC bacteremia were identified. Most cases were hospital-acquired (79.2%), and the most common source was a central venous catheter (CVC) (42.1%). The rates of susceptibility to trimethoprim-sulfamethoxazole and piperacillin-tazobactam of BCC isolates were high as 92.8% and 90.3%, respectively. The rates of susceptibility to ceftazidime, meropenem, and levofloxacin were 75.5%, 72.3%, and 64.1%, respectively. The 14-day, 30-day, and in-hospital mortality rate was 19.4%, 23.1%, and 31.0%, respectively. Female (OR = 3.1; 95% CI, 1.4-6.8), liver cirrhosis (OR = 6.2; 95% CI, 1.6-16.6), septic shock (OR = 11.2; 95% CI, 5.1-24.8), and catheter-related infection (OR = 2.6, 95% CI, 1.2-5.8) were the independent risk factors for 30-day mortality. The outcome did not differ according to type of antibiotics used. Among 91 patients with CVC-related BCC bacteremia, delayed CVC removal (> 3 days) had a higher rate of persistent bacteremia (54.5 vs. 26.1%; P = 0.03) and lower rate of clinical response (49.0 vs. 71.9%; P = 0.04), compared with early CVC removal (within 3 days). BCC bacteremia occurring in non-CF patients was mostly hospital-acquired and CVC-related. Early removal of the catheter is crucial in treatment of CVC-related BCC bacteremia.


Safety considerations for erythropoietin treatment in patients with cancer.
Cancer-related anaemia, which affects many patients with cancer, can effectively be treated by erythropoietic proteins. Erythropoietic proteins increase haemoglobin levels, reduce the risk for transfusions and also improve the quality of life of patients. When used according to published practice guidelines, these proteins benefit many patients and are generally well tolerated. Important side effects are hypertension and thromboembolic events, either of which occurs in < 10% of the patients. Administration only in anaemic patients, avoidance of target haemoglobin levels > 130 g/l, proper dose adjustments and close monitoring during treatment will ensure the clinical safety of these proteins. However, the association between erythropoietic proteins and outcome of anticancer therapy, including survival, requires further study.


Neutrophil extracellular traps generation and degradation in patients with granulomatosis with polyangiitis and systemic lupus erythematosus.
Neutrophils are one of the first cells to arrive at the site of infection, where they apply several strategies to kill pathogens: degranulation, respiratory burst, phagocytosis, and release of neutrophil extracellular traps (NETs). Recent discoveries try to connect NETs formation with autoimmune diseases, like systemic lupus erythematosus (SLE) or granulomatosis with polyangiitis (GPA) and place them among one of the factors responsible for disease pathogenesis. The aim of the study was to assess the NETotic capabilities of neutrophils obtained from freshly diagnosed autoimmune patients versus healthy controls. Further investigation involved assessing NETs production among treated patients. In the latter step, NETs degradation potency of collected sera from non-treated patients was checked. Lastly, the polymorphisms of the DNASE I gene among tested subjects were checked. NETs formation was measured in a neutrophil culture by fluorometry, while degradation assessment was performed with patients' sera and extracellular source of DNA. Additionally, Sanger sequencing was used to check potential SNP mutations between patients. About 121 subjects were enrolled into this study, 54 of them with a diagnosed autoimmune disorder. Neutrophils stimulated with NETosis inducers were able to release NETs in all cases. We have found that disease affected patients produce NETs more rapidly and in larger quantities than control groups, with up to 82.5% more released. Most importantly, we showed a difference between the diseases themselves. NETs release was 68.5% higher in GPA samples when compared to SLE ones while stimulated with Calcium Ionophore. Serum nucleases were less effective at degrading NETs in both autoimmune diseases, with a reduction in degradation of 20.9% observed for GPA and 18.2% for SLE when compared with the controls. Potential therapies targeting neutrophils and NETs should be specifically tailored to the type of the disease. Since there are significant differences between NETs release and disease type, a standard neutrophil targeted therapy could prevent over-generation of traps in some cases, while in others it would deplete the cells, leaving the immune system unresponsive to primary infections.


Stable inverted small molecular organic solar cells using a p-doped optical spacer.
We report inverted small molecular organic solar cells using a doped window layer as an optical spacer. The optical spacer was used to shift the optical field distribution inside the active layers, generating more charge carriers from sunlight. In this report, N,N,N',N'-tetrakis(4-methoxyphenyl)-benzidine (MeO-TPD) was doped with 2,2-(perfluoronaphthalene-2,6-diylidene)dimalononitrile (F6-TCNNQ), a p-type dopant material. P-doped MeO-TPD was adopted as an optical spacer because it has a large energy band gap, and its conductivity can be increased by several orders of magnitude through a doping process. As a result, a power conversion efficiency of 4.15% was achieved with the doped window layer of optimized thickness. Lastly, we present significantly improved stability of the inverted devices with the MeO-TPD layer.


Artemisia dracunculus Extracts Obtained by Organic Solvents and Supercritical CO2 Produce Cytotoxic and Antitumor Effects in Mice with L5178Y Lymphoma.
We investigated the cytotoxic and antitumor effects of nine leaf extracts from Artemisia dracunculus (Tarragon). Five extracts were obtained using different organic solvents and four by supercritical CO2. The cytotoxic effects were expressed as IC50 in 100, 80, 80, 100, and 80 μg/mL by respective solvents: hexane, ethyl acetate, acetone, ethanol, and acetonitrile in L5178Y lymphoma cells. For supercritical CO2 extract A, IC50 was 100 μg/mL; for extracts C and D, IC50 was 150 μg/mL. The antitumor activity was assessed through a tumor growth inhibition test that measured ascites fluid volume and tumor cell counts of BALB/c mice (2 × 104 cells L5178Y i.p.). Twenty-four hours after inoculation, mice were treated with 100 mg/kg of acetonitrile extract or extract SF-A daily for 15 days in independent groups of five mice, using two administration routes. We observed tumor evolution with and without treatment. Without treatment, tumor evolution was 17,969 × 106 ± 5485 L5178Y cells in 2.6 mL ascites volume, whereas the orally treated acetonitrile extract group showed 0.1 × 106 ± 0.07 L5178Y cells (P < .05). The oral SF-A group showed 12.9 × 106 ± 243 L5178Y cells, and intraperitoneal (i.p.)-treated SF-A group showed 0.1 × 106 ± 0.05 L5178Y cells (P < .05) without any ascites volume development. The acetonitrile extract contains abundant polyphenols and possibly a flavone with antioxidant activity. The SF-A contains abundant alkamides. Both extracts are complexes and the identity of the compounds responsible for observed antitumor activity remains unknown.


Adding Weekly Intramuscular Progesterone to a Twice Daily Vaginal Progesterone Capsule for Luteal Phase Support in IVF/ICSI Cycles Results in Similar Live Birth Rates.
To compare pregnancy outcomes in patients undergoing artificial reproductive treatment (ART) and fresh embryo transfer (ET) who received twice-daily vaginal progesterone capsule (Cyclogest) alone verses twice daily vaginal progesterone capsule (Cyclogest) plus weekly intramuscular Hydroxyprogesterone Capronate (Proluton depot) for luteal phase support. A retrospective cohort study that included 1162 patients who completed fresh ART/ET cycle from January 2015 to April 2018. Vaginal Cyclogest 400 mg twice daily was given to 985 patients following oocytes retrieval; whereas 177 patients received weekly intramuscular Proluton depot 250 mg in addition to twice-daily Cyclogest. The primary outcome was live birth rate. The secondary outcomes included biochemical pregnancy rate, clinical pregnancy, biochemical, and early and late pregnancy loss. There was no difference between the twice-daily vaginal progesterone and the addition of weekly intramuscular progesterone injections to the twice-daily vaginal progesterone regarding a positive pregnancy test (40.5% and 46.9%, respectively, p=0.112). There was no statistical difference in live birth rates between the groups (24% for group one, 26% for group two, p=0.582). The administration of weekly intramuscular progesterone in addition to twice-daily vaginal progesterone capsule for luteal phase support post ART cycle does not result in higher live birth rate.


A case of a bilateral accessory digastric muscle.
Abnormalities of the anterior belly of the digastric muscle are rare but have received increased attention by radiologists in recent years in an attempt to avoid confusion with submental cysts or enlarged submental lymph nodes on CT or MR images. We present a case of bilateral accessory digastric muscles which fuse (partially) with the midline raphe of the mylohyoid muscle. Fibres from the right accessory anterior digastric muscle proceeded to decussate and join the mylohyoid muscle and the contralateral insertion of the digastric muscle. Embryological development and possible clinical consequences are discussed.


Expression of the beta-adrenergic receptor-adenylylcyclase system in basal and columnar airway epithelial cells.
Catecholamines acting through the beta-adrenergic receptor (beta AR) coupled-adenylylcyclase system stimulate a variety of responses by airway epithelial cells which affect airway caliber and the response to inflammatory stimuli. Although the tracheobronchial epithelium (TBE) is composed of several phenotypically differentiated cell types, surprisingly little is known about the expression of the beta AR system by the major subpopulations of TBE cells (i.e., basal and columnar). We, therefore, examined the function of the beta AR system in columnar and basal cell-enriched populations of rabbit tracheocytes. Cells were collected from 35 rabbits in 17 separate experiments and separated into basal and columnar cell-enriched fractions by centrifugal elutriation. The columnar fraction demonstrated a significantly greater (P < 0.005) adenosine 3',5'-cyclic monophosphate (cAMP) response to isoproterenol (10(-9)-10(-5) M) than the basal cell-enriched fraction (i.e., 74.7 +/- 5.1 and 49.4 +/- 2.8 pmol/10(6) cells, in columnar and basal cell-enriched fractions, respectively, P < 0.0001) as well as a higher beta AR density (i.e., 8,678 +/- 840 and 4,754 +/- 406 beta AR sites/cell, respectively, P < 0.0001). However, when corrected for differences in cell size assessed from measurements of total cell protein, cAMP production per milligram protein and beta AR density per milligram protein were similar in the two cell fractions (P > 0.50 for both comparisons). beta AR subtype assessed by beta 1AR and beta 2AR subtype selective antagonists demonstrated that the beta 2AR subtype predominated (i.e., > 90%) in both cell populations (P > 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)


Angiotensin II Type 1 receptor antagonists in chronic heart failure.
Angiotensin II Type 1 receptor antagonists share most but not all of their pharmacological actions with angiotensin-converting enzyme inhibitors. The latter belong to standard heart failure therapy, with proven benefit in terms of morbidity and mortality. Promising data have been provided for angiotensin II Type 1 receptor antagonists in experimental models of heart failure. In patients with hypertension and those with diabetic nephropathy, favourable results have been observed with regards to blood pressure control, reversibility of structural changes or prevention of progression of disease. The currently available clinical trials in heart failure patients with angiotensin II Type 1 receptor antagonists suggest that they may be equivalent to angiotensin-converting enzyme inhibitors, but superiority has not been proven. There is no doubt about their effectiveness with regards to symptoms; however, their effect on hospitalisation and mortality is not unequivocally demonstrated. Further trials are warranted, particularly to define their role in comparison with and in addition to angiotensin-converting enzyme inhibitors and to further characterise heart failure patient populations who derive benefit from angiotensin II Type 1 receptor blockers above and beyond angiotensin-converting enzyme inhibitors, beta-blockers and spironolactone.


Partition of calcium, phosphate, and protein in the fluid phase aspirated at calcifying sites in epiphyseal cartilage.
A reproducible method, adapted from renal micropuncture techniques, was developed for sampling 10-40 mmul of a clear fluid from epiphyseal cartilage of normal or rachitic rats in vivo, either from the hypertrophic cell zone (C(f1)) or surface resting cell cartilage (L(f1)). Characterization of this fluid depended upon quantitation of protein, total inorganic phosphate (P(it)), total calcium (Ca(t)), nucleotide, and hemoglobin in volumes of 20 mmul. Established methods for macroscale measurements of each of these parameters have been modified to permit direct spectrophotometric readings on samples of 10(-10)-10(-11) g. The fluid from hypertrophic and peripheral resting cell cartilage was of an extracellular nature as evidenced by a high chloride and sodium, as well as low potassium, protein, and nucleotide content. The pH of fluid isolated from endochrondral plates in vivo was measured under oil as a function of P(CO2) and the computed bicarbonate was elevated above concurrent serum levels. After ultracentrifugation of C(f1) of normal, rachitic, and healing rachitic animals, nonprotein-bound calcium (Ca(f)) and phosphate (P(if)) were determined on supernatant fluids. The hypertrophic cell cartilage fluid of rachitic rats was distinguished by a high ratio C(f1)/serum of P(if). This ratio returned to normal during treatment of rickets. The upper limit for ionic activity A(1) Ca(++) x A HPO(4) (=) was too low to initiate precipitation of brushite or dicalcium phosphate but was in a range of supersaturation in respect to crystalline apatites. Thus these data are consistent with initiation of calcification by heterogeneous nucleation of mineral in the septal matrix but can be reconciled alternately with a precipitation mechanism only if the site of initial mineral phase separation is outside the septal matrix.


Stress enhances model-free reinforcement learning only after negative outcome.
Previous studies found that stress shifts behavioral control by promoting habits while decreasing goal-directed behaviors during reward-based decision-making. It is, however, unclear how stress disrupts the relative contribution of the two systems controlling reward-seeking behavior, i.e. model-free (or habit) and model-based (or goal-directed). Here, we investigated whether stress biases the contribution of model-free and model-based reinforcement learning processes differently depending on the valence of outcome, and whether stress alters the learning rate, i.e., how quickly information from the new environment is incorporated into choices. Participants were randomly assigned to either a stress or a control condition, and performed a two-stage Markov decision-making task in which the reward probabilities underwent periodic reversals without notice. We found that stress increased the contribution of model-free reinforcement learning only after negative outcome. Furthermore, stress decreased the learning rate. The results suggest that stress diminishes one's ability to make adaptive choices in multiple aspects of reinforcement learning. This finding has implications for understanding how stress facilitates maladaptive habits, such as addictive behavior, and other dysfunctional behaviors associated with stress in clinical and educational contexts.


The Role of Oxidative Stress in Diabetic Neuropathy: Generation of Free Radical Species in the Glycation Reaction and Gene Polymorphisms Encoding Antioxidant Enzymes to Genetic Susceptibility to Diabetic Neuropathy in Population of Type I Diabetic Patients.
Diabetic neuropathy (DN) represents the main cause of morbidity and mortality among diabetic patients. Clinical data support the conclusion that the severity of DN is related to the frequency and duration of hyperglycemic periods. The presented experimental and clinical evidences propose that changes in cellular function resulting in oxidative stress act as a leading factor in the development and progression of DN. Hyperglycemia- and dyslipidemia-driven oxidative stress is a major contributor, enhanced by advanced glycation end product (AGE) formation and polyol pathway activation. There are several polymorphous pathways that lead to oxidative stress in the peripheral nervous system in chronic hyperglycemia. This article demonstrates the origin of oxidative stress derived from glycation reactions and genetic variations within the antioxidant genes which could be implicated in the pathogenesis of DN. In the diabetic state, unchecked superoxide accumulation and resultant increases in polyol pathway activity, AGEs accumulation, protein kinase C activity, and hexosamine flux trigger a feed-forward system of progressive cellular dysfunction. In nerve, this confluence of metabolic and vascular disturbances leads to impaired neural function and loss of neurotrophic support, and over the long term, can mediate apoptosis of neurons and Schwann cells, the glial cells of the peripheral nervous system. In this article, we consider AGE-mediated reactive oxygen species (ROS) generation as a pathogenesis factor in the development of DN. It is likely that oxidative modification of proteins and other biomolecules might be the consequence of local generation of superoxide on the interaction of the residues of L-lysine (and probably other amino acids) with α-ketoaldehydes. This phenomenon of non-enzymatic superoxide generation might be an element of autocatalytic intensification of pathophysiological action of carbonyl stress. Glyoxal and methylglyoxal formed during metabolic pathway are detoxified by the glyoxalase system with reduced glutathione as co-factor. The concentration of reduced glutathione may be decreased by oxidative stress and by decreased in situ glutathione reductase activity in diabetes mellitus. Genetic variations within the antioxidant genes therefore could be implicated in the pathogenesis of DN. In this work, the supporting data about the association between the -262T > C polymorphism of the catalase (CAT) gene and DN were shown. The -262TT genotype of the CAT gene was significantly associated with higher erythrocyte catalase activity in blood of DN patients compared to the -262CC genotype (17.8 ± 2.7 × 10(4) IU/g Hb vs. 13.5 ± 3.2 × 10(4) IU/g Hb, P = 0.0022). The role of these factors in the development of diabetic complications and the prospective prevention of DN by supplementation in formulations of transglycating imidazole-containing peptide-based antioxidants (non-hydrolyzed carnosine, carcinine, n-acetylcarcinine) scavenging ROS in the glycation reaction, modifying the activity of enzymic and non-enzymic antioxidant defenses that participate in metabolic processes with ability of controlling at transcriptional levels the differential expression of several genes encoding antioxidant enzymes inherent to DN in Type I Diabetic patients, now deserve investigation.


Energy and redox homeostasis in tumor cells.
Cancer cells display abnormal morphology, chromosomes, and metabolism. This review will focus on the metabolism of tumor cells integrating the available data by way of a functional approach. The first part contains a comprehensive introduction to bioenergetics, mitochondria, and the mechanisms of production and degradation of reactive oxygen species. This will be followed by a discussion on the oxidative metabolism of tumor cells including the morphology, biogenesis, and networking of mitochondria. Tumor cells overexpress proteins that favor fission, such as GTPase dynamin-related protein 1 (Drp1). The interplay between proapoptotic members of the Bcl-2 family that promotes Drp 1-dependent mitochondrial fragmentation and fusogenic antiapoptotic proteins such as Opa-1 will be presented. It will be argued that contrary to the widespread belief that in cancer cells, aerobic glycolysis completely replaces oxidative metabolism, a misrepresentation of Warburg's original results, mitochondria of tumor cells are fully viable and functional. Cancer cells also carry out oxidative metabolism and generally conform to the orthodox model of ATP production maintaining as well an intact electron transport system. Finally, data will be presented indicating that the key to tumor cell survival in an ROS rich environment depends on the overexpression of antioxidant enzymes and high levels of the nonenzymatic antioxidant scavengers.


Chemical Potential Characterization of Symmetry-Breaking Phases in a Rhombohedral Trilayer Graphene.
Rhombohedral trilayer graphene has recently emerged as a natural flat-band platform for studying interaction-driven symmetry-breaking phases. The displacement field (D) can further flatten the band to enhance the density of states, thereby controlling the electronic correlation that tips the energy balance between spin and valley degrees of freedom. To characterize the energy competition, chemical potential measurement─a direct thermodynamic probe of Fermi surfaces─is highly demanding to be conducted under a constant D. In this work, we characterize D-dependent isospin flavor polarization, where electronic states with isospin degeneracies of one and two can be identified. We also developed a method to measure the chemical potential at a fixed D, allowing for the extraction of energy variation during phase transitions. Furthermore, symmetry breaking could also be invoked in Landau levels, manifesting as quantum Hall ferromagnetism. Our work opens more opportunities for the thermodynamic characterization of displacement-field tuned van der Waals heterostructures.


Is the decline in diagnoses of schizophrenia caused by the disappearance of a seasonal aetiological agent? An epidemiological study in England and Wales.
Studies from several countries have shown a decline, in the last few decades, of the number of admissions with a diagnosis of schizophrenia. This could be due to a fall in the incidence of schizophrenia, but it also could be due to confounding factors. The hypothesis tested in the study is that the incidence of schizophrenia is actually falling because of a decrease in the presence of a seasonal aetiological agent. The hypothesis was tested by analysing the dates of birth of the patients discharged with a diagnosis of schizophrenia from NHS hospitals in England and Wales and would be confirmed by an appropriate change in the seasonality of the births over time. Evidence of seasonality has been observed in the schizophrenic births, but with no significant change over time. The fall in first admissions with a diagnosis of schizophrenia does not seem to be due to a change in the prevalence of a seasonal aetiological factor. Therefore, either there has been a reduction in incidence due to a change in a non-seasonal agent, or the incidence of schizophrenia is not changing and the fall in first admissions is due to confounding factors.


A systematic review of microwave-based therapy for axillary hyperhidrosis.
To systematically analyse the literature on the use of the microwave-based device for subdermal thermolysis of the axilla and its efficacy for the treatment of axillary hyperhidrosis. A systematic review was conducted using PubMed, Embase, SCOPUS and Cochrane databases on 2 June 2016. The inclusion criteria including: (1) studies with human subjects, (2) full-text articles published in English, (3) a microwave-based device used to treat axillary hyperhidrosis and (4) trials that precisely evaluated axillary hyperhidrosis. Exclusion criteria were the following: (1) studies that did not fit the inclusion criteria mentioned above and (2) case reports and reviews. We reviewed five clinical trials and 189 patients, all of which were published between 2012 and 2016. There was one randomized controlled trial, one retrospective study and the remainder were prospective studies. Although all of the studies were conducted with a small sample size, the results indicated that microwave-based device treatment of axillary hyperhidrosis had long-term efficacy with mild adverse effects. In addition, most patients were satisfied with the outcomes in these studies. Microwave-based device treatment may be an effective alternative treatment for axillary hyperhidrosis. However, further investigation is necessary to determine its long-term efficacy and safety.


[Etiological characteristics of hand, foot and mouth disease in Yangzhou from 2015 to 2019].
To understand the prevalence and etiological characteristics of hand, foot and mouth disease(HFMD) in Yangzhou, so as to provide scientific basis for prevention and control of HFMD. HFMD cases from six sentinel hospitals in Yangzhou from January 2015 to December 2019 were taken as the subject of study. The epidemiological data of HFMD were analyzed by descriptive epidemiology method, the enterovirus were detected using RT-PCR method and the etiological characteristics were analyzed. The data were collected by Excel 2007 and statistically analyzed by SPSS22.0 software. A total of 1 151 positive cases were detected from all 2 129 HFMD clinical specimens collected in Yangzhou from 2015 to 2019, with a total positive rate of 54.06%, including 148 cases of EV71(6.95%), 382 cases of CA16(17.94%) and 621 cases of other enterovirus(29.17%). The difference of positive rate in different years(χ2=99.28, P<0.05), different months(χ2=92.09, P<0.05) and different districts(χ2=71.39, P<0.05)was statistically significant. Each subtype of enterovirus showed alternating prevalence in different years. The peak period of detection rate was from April to September (720 cases, 62.55%). The reported incidence for males was higher than females, with the male-female ratio of 1.58∶1 and children under six (971 cases, 84.36%) as the major attacked population. There were obvious seasonal, regional and population characteristics of HFMD in Yangzhou City from 2015 to 2019. It reminds us that surveillance of HFMD should be continually implemented, more attention should be paid to the prevention and control of key population in high-risk seasons, and the booming HFMD cases caused by other enterovirus should be emphasized especially.


Determinants of the p28 cleavage site recognized by the first papain-like cysteine proteinase of murine coronavirus.
The murine coronavirus polymerase gene is 22 kb in length with the potential to encode a polyprotein of approximately 750 kDa. The polyprotein has been proposed to encode three proteinase domains which are responsible for the processing of the polyprotein into mature proteins. The proteolytic activity of the first proteinase domain has been characterized and resembles the papain family of cysteine proteinases. This proteinase domain acts autoproteolytically to cleave the amino terminal portion of the polymerase polyprotein, releasing a 28-kDa protein designated p28. To identify the cleavage site of this papain-like cysteine proteinase, we isolated the peptide adjacent to p28 and determined the amino terminus sequence by Edman degradation reaction. We report that proteolysis occurs between the Gly-247 and Val-248 dipeptide bond. To determine the role of the amino acid residues surrounding the cleavage site, we introduced a total of 42 site-specific mutations at the residues spanning the P5 to P3' positions and assessed the effects of the mutations on the processing of p28 in an in vitro transcription and translation system. The substitutions of Gly-247 at the P1 position or Arg-246 at the P2 position resulted in a dramatic decrease of proteolytic activity, and the mutations of Arg-243 at P5 position also led to considerable reduction in p28 cleavage. In contrast, the substitutions of amino acids Gly-244 (P4), Tyr-245 (P3), Val-248 (P1'), Lys-249 (P2'), and Pro-250 (P3') had little or no effect on the amount of p28 that was released. This work had identified Gly-247-Val-248 as the cleavage site for the release of p28, the amino-terminal protein of the murine coronavirus polymerase polyprotein. Additionally, we conclude that the Gly-247 and Arg-246 are the major determinants for the cleavage site recognition by the first papain-like cysteine proteinase of murine coronavirus.


The complications of therapeutic plasma exchange.
We reviewed a series of 181 patients who were treated with therapeutic plasma exchange ( TPE ) a total of 1,389 times. Complications were associated with 22 (1.6%) of the procedures and involved 20 (11%) of the patients. Six of the complications were of a technical nature and did not affect the medical conditions of the patients. 8 patients developed the following serious medical problems: unexplained death during the post- TPE period, myocardial infarction, pulmonary embolus, loss of consciousness, myocardial ischemia, cerebral ischemia and chest pain. Although these problems were temporally associated with TPE none of them could be attributed to the TPE with certainty. The remaining eight medical complications were of a less serious nature.


Radioimmunoassay of human urinary kallikrein: determination of human urinary kallikrein, II.
A radioimmunoassay for the determination of human urinary kallikrein was developed. The sensitivity of the assay was 0.5 microgram/l. Dose-response curves of human submandibular and parotid saliva, sweat, pancreatic juice and bile paralleled the standard curve obtained with purified human urinary kallikrein. Substances with similar antigenic determinants were also found in human serum, ascites, seminal plasma, amniotic fluid, cervical mucus, tears, liquor and faeces, but not in human breast milk and gastric juice. Moreover, immunoreactive material was detected in the urine of guinea pigs, orangoutangs and chimpanzees, but not in the urine of rats, cats and rabbits. Porcine acrosin and kallikrein, as well as bovine trypsin and chymotrypsin, showed no cross reactivity.


Iron status of some pregnant women in Orlu town--eastern Nigeria.
High prevalence of anaemia has been reported among pregnant women especially in developing nations. This paper considers maternal haemoglobin (Hb) level, serum total iron, iron binding capacity, and serum ferritn iin antenatal women in Orlu-Imo State Nigeria. Haemoglobin level, serum iron, serum ferritin, and total iron binding capacity (TIBC) were measured in different trimesters among 90 pregnant women aged 20-45 years, on iron supplements attending antenatal clinic of Imo State University Teaching Hospital Orlu. First trimester comprised of 16.7% (n = 15), second trimester comprised of 50% (n = 45) while as third trimester comprised of 33.3% (n = 30). 30 non-pregnant women aged 26-40 years were used as controls. The mean Hb level was 11.28 +/- 1.4 g/dl in first trimester, 9.51 +/- 1.9 g/dl in second trimester, 10.4 +/- 1.2 g/dl in third trimester, and 10.9 +/- 1.5 g/dl in controls. Mean serum iron level was 142 +/- 23 microg/ml in first trimester, 235 +/- 118 microg/ml in second trimester, 251 +/- 118 microg/ml in third trimester, and 99.7 +/- 19.4 microg/ml in controls. Mean serum ferritin was 57.7 +/- 30 ng/ml in first trimester, 37.6 +/- 17 ng/ml in second trimester, 37.3 +/- 20 ng/ml in third trimester, and 86.7 +/- 16.9 ng/ml in controls TIBC was 337 +/- 90 microg/dl in first trimester, 441 +/- 19 microg/dl in second trimester, 482 +/- 149 microg/dl in third trimester and 271.8 +/- 89.0 microg/ml in controls. Hb level was relatively stable in pregnancy, but was significantly (p < 0.05) lowest in the second trimester compared with controls Serum iron and TIBC progressively increased from first trimester to third trimester. Conversely, serum ferritin declined progressively from first trimester to third trimester. The increments in serum iron was statistically significant (p < 0.05) between first and second trimester, but not significant between second and third trimester. TIBC was significantly higher in third trimester compared with first trimester. Serum ferritin was significantly lower in second and third trimesters compared with controls. This implies a progressive mineral transfer from mother to fetus. TIBC and serum iron were significantly (p 0.05) lowest in non-pregnant controls compared with the three trimesters of pregnancy. Conversely ferritin was significantly (p < 0.05) higher among the non-pregnant controls compared with the three trimesters of pregnancy. This implies that the nonpregnant women had more iron store and had less iron need than their pregnant counterpart. The higher iron need in pregnancy necessitated its mobilization from its stores. This study encourages more critical antenatal care especially at second trimester of pregnancy with much emphasis on dietary supplementation of iron and minerals through adequate consumption of local vegetables and other food diets rich in iron. There was poorest antenatal attendance in the first trimester. Pregnant women in this environment should be encouraged to register early for antenatal care.


Cytogenetic studies on recipients of allogeneic bone marrow using the sex chromosomes as markers of cellular origin.
In 45 patients whose donor was of unlike sex, the sex chromosomes were used as markers of the cellular origin of myeloid and lymphoid tissues after allogeneic bone marrow transplantation (BMT). Successful engraftment was characterized by the appearance of dividing donor cells in marrow within 2 weeks of grafting and in mitogen stimulated blood cultures by 3 weeks. Leukaemic relapse was identified in eight cases and was associated with different patterns of cellular origin of the myeloid and lymphoid tissues. At the time of relapse the marrow contained either a mixed population of normal donor and leukaemic recipient cells, or only recipient cells. Thus, in this series, leukaemic relapse was not found occurring in donor cells. The importance of defining the origin of cells in interphase as well as in metaphase was demonstrated. In all but one case, the dividing lymphoid population remained of donor origin during relapse.


Software development for emergency bed management.
to describe the process of developing a software for emergency bed management. a participatory research based on User-Centered Design in four stages: 1) definition of requirements and structure elaboration; 2) generation of alternatives and prototyping; 3) tests; 4) implementation. Seminars were held with health professionals between May 21, 2018 and May 31, 2019 for the preparation and assessment of software content. the software CuidarTech KRONOS was developed for emergency bed management using the kanban methodology. this software will assist professionals' and managers' decision-making providing more reliable data to enable the improvement of work processes and the quality of patient care. Developing a bed management software is innovative in the health field, and no articles were found describing this methodology.


Forecast models for suicide: Time-series analysis with data from Italy.
The prediction of suicidal behavior is a complex task. To fine-tune targeted preventative interventions, predictive analytics (i.e. forecasting future risk of suicide) is more important than exploratory data analysis (pattern recognition, e.g. detection of seasonality in suicide time series). This study sets out to investigate the accuracy of forecasting models of suicide for men and women. A total of 101 499 male suicides and of 39 681 female suicides - occurred in Italy from 1969 to 2003 - were investigated. In order to apply the forecasting model and test its accuracy, the time series were split into a training set (1969 to 1996; 336 months) and a test set (1997 to 2003; 84 months). The main outcome was the accuracy of forecasting models on the monthly number of suicides. These measures of accuracy were used: mean absolute error; root mean squared error; mean absolute percentage error; mean absolute scaled error. In both male and female suicides a change in the trend pattern was observed, with an increase from 1969 onwards to reach a maximum around 1990 and decrease thereafter. The variances attributable to the seasonal and trend components were, respectively, 24% and 64% in male suicides, and 28% and 41% in female ones. Both annual and seasonal historical trends of monthly data contributed to forecast future trends of suicide with a margin of error around 10%. The finding is clearer in male than in female time series of suicide. The main conclusion of the study is that models taking seasonality into account seem to be able to derive information on deviation from the mean when this occurs as a zenith, but they fail to reproduce it when it occurs as a nadir. Preventative efforts should concentrate on the factors that influence the occurrence of increases above the main trend in both seasonal and cyclic patterns of suicides.


Changes in hemodynamic and post-flights orthostatic tolerance of cosmonauts under application of the preventive device--thigh cuffs bracelets in short-term flights.
to evaluate the influence of the use thigh cuffs "Bracelet" on the hemodynamic adaptation to microgravity during short-term (up to a month) space flights, in-flight tolerance to LBNP-tests and post-flight orthostatic tolerance. 6 cosmonauts applied and 7 others did not apply the occlusive cuffs when on flight. The "Bracelet" device notably relieved the cosmonauts from the subjective discomfort following by the blood redistribution at initial period of exposure to microgravity. It was established that "Bracelet" lessened shifts in central and peripheral hemodynamics typical for exposure to microgravity, venous stasis in the cervical-cephalic region in particular. There were no differences between the hemodynamic reaction on LBNP-test in cosmonauts who applied and not applied "Bracelet" during short-term flights. The objective data are received, that the application of the device during short-term space flight does not make negative effects on post-flight orthostatic tolerance.


Addressing Ethnic Disparities in Adolescent Smoking: Is Reducing Exposure to Smoking in the Home a Key?
Smoking among New Zealand (NZ) adolescents has declined since 2000, but ethnic disparities remain pronounced. To inform prevention efforts, we investigated exposure to and relative importance of known predictors of adolescent smoking and how these have changed over time, for Māori (NZ's indigenous population) and adolescents overall. We used repeat cross-sectional data, 2003-2015, from a national survey of 14- to 15-year olds (N = 20 443-31 696 per year). For the overall sample and for Māori and non-Māori, we calculated adjusted odds ratios (aORs) to assess the association between regular smoking and risk factors each year: one or more parents smoke, best friend smokes, older sibling(s) smoke, and past week exposure to smoking in the home. We calculated population attributable risk (PAR) for risk factors in 2003 and 2015. Between 2003 and 2015, aORs for exposure to smoking in the home increased from 1.7 (95% CI 1.6% to 1.8%) to 2.6 (2.1% to 3.1%) overall and from 1.8 (1.6% to 2.1%) to 3.4 (2.5% to 4.5%) for Māori; aORs for "best friend smokes" also increased, while aORs for sibling smoking and parental smoking did not change meaningfully. PAR for exposure to smoking in the home increased from 17% to 31% overall and from 28% to 57% for Māori, while PARs for other risk factors decreased. Exposure to smoking in the home has become more strongly associated with adolescent smoking over time and is an increasingly important risk factor at the population level (independent of parental smoking), particularly for Māori. Our findings have implications for reducing smoking uptake and ethnic disparities in NZ, and potentially elsewhere, given the similarity in risk factors and trends for adolescent smoking internationally. Our findings suggest that reducing second-hand smoke exposure in homes will likely reduce uptake of smoking. Because Māori children are both more exposed and appear to be more strongly influenced by exposure to smoking in the home, interventions to reduce indoor smoking could have differentially positive effects for Māori. Greater research and policy attention to reducing smoking in homes is warranted.