Differences in Outflow Facility Between Angiographically Identified High- Versus Low-Flow Regions of the Conventional Outflow Pathways in Porcine Eyes.
To investigate differences in outflow facility between angiographically determined high- and low-flow segments of the conventional outflow pathway in porcine eyes. Porcine anterior segments (n = 14) were mounted in a perfusion chamber and perfused using Dulbecco's phosphate buffered solution with glucose. Fluorescein angiography was performed to determine high- and low-flow regions of the conventional outflow pathways. The trabecular meshwork (TM) was occluded using cyanoacrylate glue, except for residual 5-mm TM areas that were either high or low flow at baseline, designating these eyes as "residual high-flow" or "residual low-flow" eyes. Subsequently, outflow was quantitatively reassessed and compared between residual high-flow and residual low-flow eyes followed by indocyanine green angiography. Fluorescein aqueous angiography demonstrated high-flow and low-flow regions. Baseline outflow facilities were 0.320 ± 0.08 and 0.328 ± 0.10 µL/min/mmHg (P = 0.676) in residual high-flow and residual low-flow eyes before TM occlusion, respectively. After partial trabecular meshwork occlusion, outflow facility decreased to 0.209 ± 0.07 µL/min/mmHg (-32.66% ± 19.53%) and 0.114 ± 0.08 µL/min/mmHg (-66.57% ± 23.08%) in residual high- and low-flow eyes (P = 0.035), respectively. There was a significant difference in the resulting IOP increase (P = 0.034). Angiographically determined high- and low-flow regions in the conventional outflow pathways differ in their segmental outflow facility; thus, there is an uneven distribution of local outflow facility across different parts of the TM.


The noncompetitive blocker [3H]chlorpromazine labels three amino acids of the acetylcholine receptor gamma subunit: implications for the alpha-helical organization of regions MII and for the structure of the ion channel.
Labeling studies of Torpedo marmorata nicotinic acetylcholine receptor with the noncompetitive channel blocker [3H]chlorpromazine have led to the initial identification of amino acids plausibly participating to the walls of the ion channel on the alpha, beta, and delta subunits. We report here results obtained with the gamma subunit, which bring additional information on the structure of the channel. After photolabeling of the membrane-bound receptor under equilibrium conditions in the presence of agonist and with or without phencyclidine (a specific ligand for the high-affinity site for noncompetitive blockers), the purified labeled gamma subunit was digested with trypsin, and the resulting fragments were fractionated by HPLC. Sequence analysis of peptide mixtures containing various amounts of highly hydrophobic fragments showed that three amino acids are labeled by [3H]chlorpromazine in a phencyclidine-sensitive manner: Thr-253, Ser-257, and Leu-260. These residues all belong to the hydrophobic and putative transmembrane region MII of the gamma subunit. Their distribution along the sequence is consistent with an alpha-helical organization of this segment. The [3H]chlorpromazine-labeled amino acids are conserved at homologous positions in the known sequences of other ligand-gated ion channels and may, thus, play a critical role in ion-transport mechanisms.


Levitated Plasmonic Nanoantennas in an Aqueous Environment.
We report on the manipulation of a plasmonic nanoantenna in an aqueous solution using an electrostatic trap created between a glass nanopipette and a substrate. By scanning a trapped gold nanosphere in the near field of a single colloidal quantum dot embedded under the substrate surface, we demonstrate about 8-fold fluorescence enhancement over a lateral full width at half-maximum of about 45 nm. We analyze our results with the predictions of numerical electromagnetic simulations under consideration of the electrostatic free energy in the trap. Our approach could find applications in a number of experiments, where plasmonic effects are employed at liquid-solid interfaces.


Electronic medication monitor for people with tuberculosis: Implementation experience from thirty counties in China.
China piloted a digital adherence technology called electronic medication monitor (EMM) to support self-administered treatment for tuberculosis. EMM is a portable plastic box that records each time the device is opened, offering an indirect measure of treatment adherence. During the monthly patient visits to tuberculosis designated hospitals, the doctors access the data from the EMM. Among people with tuberculosis notified in 30 counties in China (July-December 2018) where EMM supported self-administered treatment was suggested to all those eligible (no communication impairment, ambulatory care), we assessed the i) proportion eligible for using EMM ii) uptake of EMM and factors associated and iii) treatment adherence, including the proportion shifted to DOT. This was an observational study using secondary programme data. Single instance of ≥50% or continued instance of 20-49% monthly missed doses was the eligibility criteria to shift to DOT. We used log binomial regression to identify factors associated with not using EMM within first month. Of 2227 with EMM eligibility data, 1810 (81%) were eligible for EMM. Of 1810 people, 1314 (73%) ever used EMM anytime during treatment, among them, 134 (10%) were eligible for shift to DOT (based on EMM data), and 29 (22%) were shifted. In addition, 70 were shifted while the EMM data was missing. Of 1047 people who started using EMM within first month, we observed 6381 person-months of follow up and there were 1526(25%) instances of missing EMM data. Children (<15 years), elderly (≥65 years), semi-skilled or unemployed people, people with tuberculosis pleurisy and previous tuberculosis treatment were less likely to use EMM within first month. The EMM uptake was satisfactory but shift to DOT has to be ensured based on adherence data from EMM. The subsequent follow-up action when EMM data is missing has to be clarified in the guidelines.


Sexual problems after total or partial laryngectomy.
To investigate sexual problems that can occur after laryngeal and hypopharyngeal cancer surgery and to specify possible influencing factors. Multi-institutional cross-sectional study. Two hundred six patients were interviewed in person using the European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire, Head and Neck Module (EORTC QLQ-H&N35), the Hospital Anxiety and Depression Scale, and a structured interview assessing alcohol and tobacco consumption, sociodemographic data, and specific sexual problems. Type of surgery, tumor site, and tumor stage were documented according to the participants' medical records. Multivariate analysis of variance was used to assess the independent impact of each factor. More than half of the patients in our study reported having reduced libido and sexual enjoyment after treatment. Sixty percent considered it an important issue for their contentment with life. Sexual difficulties were found to be unrelated with gender, formal education, alcohol and tobacco consumption, type of surgery (partial vs. total laryngectomy), radiotherapy, and tumor site. Psychological distress (F = 46.27, P < .001) was seen to have a strong independent impact on the occurrence of sexual difficulties and stage of disease (F = 4.50, P < .05) and age (F = 4.79, P < .05), a moderate independent impact. Reduced libido and sexual enjoyment is a common problem after laryngeal and hypopharyngeal cancer surgery. However, it is not caused by the oncological treatment but rather by the cancer itself. Depression is often associated with sexual problems. Both should be discussed in medical consultations with head and neck cancer patients when appropriate to provide adequate treatment.


Investigating the impact of cognitive bias in nursing documentation on decision-making and judgement.
The clinical documentation of patients' mental status, behaviour and functioning is a fundamental aspect of inpatient mental health care. It is an important source of information-sharing with the interprofessional team and used by other clinicians within the circle of care to guide their decision-making process. Given the body of evidence highlighting concerns about the quality of nursing documentation and the growing literature demonstrating the presence of bias in healthcare, it is critically important that we examine the impact of this bias in nursing practice. The primary objective of this study was to determine whether clinical decisions and judgements change when nurses read documentation that is either biased or neutral. Using a quantitative, observational study that used surveys to collect data, participants were exposed to two patient vignettes and six clinical notes associated with each patient (notes were written with either biased or neutral language) and asked to make clinical decisions and judgements. Results from 199 nurse participants from a tertiary mental health hospital revealed a notable relationship between the type of notes read (biased vs. neutral) and clinical practice, namely, participants reading biased notes were less likely to offer health teaching when administering pro re nata (PRN) medication for sleep. We also found differences in decision-making and judgements based on the type of note read depending on years of experience and type of education. The results indicate that biased language in nursing documentation can influence other clinicians' decisions and judgements about patients, thereby indicating a cascade of bias.


Carbonyl Allylation and Crotylation: Historical Perspective, Relevance to Polyketide Synthesis, and Evolution of Enantioselective Ruthenium-Catalyzed Hydrogen Auto-Transfer Processes.
The evolution of methods for carbonyl allylation and crotylation of alcohol proelectrophiles culminating in the design of iodide-bound ruthenium-JOSIPHOS catalysts is prefaced by a brief historical perspective on asymmetric carbonyl allylation and its relevance to polyketide construction. Using gaseous allene or butadiene as precursors to allyl- or crotylruthenium nucleophiles, respectively, new capabilities for carbonyl allylation and crotylation have been unlocked, including stereo- and site-selective methods for the allylation and crotylation of 1,3-diols and related polyols.


Pathogens in Vasculitis: Is It Really Idiopathic?
Vasculitis is an autoimmune disease characterized by the infiltration of leukocytes in blood vessels. An increasing number of studies on human and animal models have implicated various microorganisms in the pathogenesis of vasculitis. Previous studies have shown the presence of infectious agents, including viruses, bacteria, and fungi, in diseased vessels. However, despite continued research, the link between infection and vasculitis is not fully understood, possibly owing to the lack of appropriate animal models that mirror human disease and the technical limitations of pathogen detection in blood vessels. Among the pathogen-induced animal models, Candida albicans water-soluble fraction (CAWS)-induced coronary arteritis is currently considered one of the representative models of Kawasaki (KD) disease. Advances in metagenomic next-generation sequencing have enabled the detection of all nucleic acids in tissue, which can help identify candidate pathogens, including previously unidentified viruses. In this review, we discuss the findings from reports on pathogen-associated vasculitis in animal models and humans, with a specific focus on the investigation of the pathogenesis of vasculitis. Further studies on animal models and microbes in diseased vessels may provide important insights into the pathogenesis of vasculitis, which is often considered an idiopathic disease.


Are source-filter interactions detectable in classical singing during vowel glides?
In recent studies, it has been assumed that vocal tract formants (Fn) and the voice source could interact. However, there are only few studies analyzing this assumption in vivo. Here, the vowel transition /i/-/a/-/u/-/i/ of 12 professional classical singers (6 females, 6 males) when phonating on the pitch D4 [fundamental frequency (ƒo) ca. 294 Hz] were analyzed using transnasal high speed videoendoscopy (20.000 fps), electroglottography (EGG), and audio recordings. Fn data were calculated using a cepstral method. Source-filter interaction candidates (SFICs) were determined by (a) algorithmic detection of major intersections of Fn/nƒo and (b) perceptual assessment of the EGG signal. Although the open quotient showed some increase for the /i-a/ and /u-i/ transitions, there were no clear effects at the expected Fn/nƒo intersections. In contrast, ƒo adjustments and changes in the phonovibrogram occurred at perceptually derived SFICs, suggesting level-two interactions. In some cases, these were constituted by intersections between higher nƒo and Fn. The presented data partially corroborates that vowel transitions may result in level-two interactions also in professional singers. However, the lack of systematically detectable effects suggests either the absence of a strong interaction or existence of confounding factors, which may potentially counterbalance the level-two-interactions.


Rapid structural analysis of nanomaterials in aqueous solutions.
Rapid structural analysis of nanoscale matter in a liquid environment represents innovative technologies that reveal the identities and functions of biologically important molecules. However, there is currently no method with high spatio-temporal resolution that can scan individual particles in solutions to gain structural information. Here we report the development of a nanopore platform realizing quantitative structural analysis for suspended nanomaterials in solutions with a high z-axis and xy-plane spatial resolution of 35.8 ± 1.1 and 12 nm, respectively. We used a low thickness-to-diameter aspect ratio pore architecture for achieving cross sectional areas of analyte (i.e. tomograms). Combining this with multiphysics simulation methods to translate ionic current data into tomograms, we demonstrated rapid structural analysis of single polystyrene (Pst) beads and single dumbbell-like Pst beads in aqueous solutions.


[Neisseria gonorrhoeae: an infrequent causal agent of periorbital cellulitis in a child].
Periorbital cellulitis is a very common disease in pediatric population, it describes an infection involving the adjacent soft tissues anterior to the orbital septum. Pathogens involved are generally Gram-positive cocci after introduction of Haemophilus influenzae vaccine. We report a case of Neisseria gonorrhoeae periorbital cellulitis associated with bacterial conjunctivitis in a child. There are few cases reported in the literature with this microorganism as the causal agent. With this case, we would like to emphasize the importance to do a culture of the ocular secretion (if it exists) because this allowed us to determine an infrequent agent of this disease.


Bone cell behavior on Matrigel-coated Ca/P coatings of varying crystallinities.
Rat calvarial cell mitogenic behavior was investigated on various biomaterials coated with Matrigel, a basement membrane matrix containing growth factors. Low (20-40%) and high (70-90%) crystallinity hydroxyapatite (rHA and cHA), rough titanium (Ti), and tissue culture polystyrene (TP) surfaces were compared. Surface chemistry and calcium resorption of HA coatings, alkaline phosphatase activity (APA), and growth of cells were measured for Matrigel-coated and uncoated surfaces at 2, 7, and 14 days. Gene expression for four noncollagenous bone-related proteins (osteonectin, osteopontin, alkaline phosphatase, and osteocalcin) was also investigated by reverse transcription and polymerase chain reaction up to 28 days. Ca concentration in incubating solutions increased with time for the two types of HA coatings and was always greater for rHA than cHA. Surface chemistry and coating dissolution rates were not affected by the presence of Matrigel or cells throughout the study. APA of cells on the two HA-coated surfaces was comparably enhanced in the presence of Matrigel and was greater than on Ti surfaces. Only HA surfaces showed an increased APA of cells with time in the presence of Matrigel. Cell growth peaked at 7 days and was greatest for cells on the two HA surfaces and without Matrigel. At 14 days, cell growth was comparable on the four surfaces. The presence of HA and Matrigel enhanced cell-specific APA at 14 days. Gene expression for all four proteins investigated showed no differences between surfaces after 7 days. At 2 and 7 days, gene expression was indicative of proliferation for Ti, and of proliferation, differentiation, and mineralization for HA and TP more so without Matrigel. The addition of this matrix significantly enhanced mitogenicity of calvarial cells on HA only after 14 days. Matrigel eliminated differences seen between the two HA coatings. Gene expression was not enhanced or inhibited by the presence of Matrigel.


Dicer-related drh-3 gene functions in germ-line development by maintenance of chromosomal integrity in Caenorhabditis elegans.
In the course of systematic RNA interference (RNAi)-based screens with helicase-like genes in Caenorhabditis elegans, we have identified the drh-3(D2005.5) gene as a candidate gene for protection against X-ray irradiation. This gene encodes a novel RNA helicase-like protein that is similar to two nematode Dicer-related helicases (DRH). Here, we have showed the increased expression of drh-3 transcripts during maturation of larvae to adults, and characterized the phenotype of drh-3-interferred nematodes using feeding RNAi method. RNAi-mediated depletion of the drh-3 transcripts caused embryonic lethality of F1 progeny and temperature-sensitive reproductive capacity but did not affect the nematode life span. F1 progeny from drh-3(RNAi) animals exhibited increased lethality after X-ray irradiation or exposure to camptothecin. In drh-3(RNAi) worms, aggregated chromosomes were observed in diakinesis oocyte nuclei. In developing early zygotic embryos from drh-3(RNAi) worms, abnormally segregated chromosomes were observed and embryonic development was largely arrested at the mid-stages of embryogenesis. Finally, examination of checkpoint responses in mitotic germ cells with regards to replication arrest by hydroxyurea and X-ray-induced DNA damage suggested that both checkpoints function normally under these genotoxic stress conditions. Taken together, these results indicate that the drh-3 gene is essential for the development of germ-lines by maintaining chromosomal integrity in C. elegans.


Rapid and severe proteinuria induced in rats by antibody against cultured rat glomerular epithelial cells.
The aim of this study was to investigate the role of glomerular visceral epithelial cell (GEC) antigens in the induction of proteinuria. An antibody (anti-GECIg) was produced by rabbit immunization with membrane extracts prepared from a clonal GEC line, SGE1, from the isolated rat renal glomeruli. A one-shot intraperitoneal injection of anti-GECIg (day 0) induced rapid and severe proteinuria in rats, reaching a peak on day 2 (mean value, 425 mg/24h), then gradually decreased to normal levels by day 10. By direct immunofluorescence, fine granular binding of anti-GECIg along the glomerular capillary walls was observed within 24 h. Electron microscopy and immunoelectron microscopy revealed GEC alterations consisting of extensive retraction of the foot processes, vacuolar changes in the cytoplasm, microvillous transformation of the cell surface, and binding of anti-GECIg to the surface of the foot process, mainly to its soles. Two major components with Mr of 108,000 and 39,000 were identified by immunoblotting assay using SGE1 cell membrane extracts and anti-GECIg. This model of rat nephropathy induced by anti-GECIg hopefully will lead to a greater understanding of the mechanism by which proteinuria is induced and developed.


Patients' Beliefs About Causes and Consequences of Heart Failure Symptoms.
Patients' perceptions of the causes and consequences of heart failure (HF) symptoms may impact effective self-management. The purpose of this study was to describe and explore patients' perceptions of HF symptom status and the causes and consequences on their daily lives in patients with HF. Descriptive and qualitative data were obtained from 20 patients using a semistructured interview guide. Data were analyzed using content analysis and descriptive statistics. Participants reported 15 symptoms (median = 4). Five themes were (a) multiple causes and multiple symptoms; (b) knowing some causes, but still unclear; (c) not being able to live life as previously did; (d) facing emotional distress due to HF symptoms; and (e) development of new priorities and lifestyles. The findings demonstrate that all participants perceived considerable difficulties living with HF symptoms. More comprehensive interventions need to be delivered to patients to manage multiple causes and symptoms effectively.


Verner-Morrison syndrome. Literature review.
Chronic diarrhea in infants is a common condition for addressability to pediatric gastroenterologists. The causes are multiple and the delay in reaching the final diagnosis can lead to complications in the general condition of the child. The purpose of this review is to present the bio-clinical and histogenetic particularities of a rare clinical entity, characterized by tumoral causes of chronic diarrhea. VIPomas are neuroendocrine tumors that autonomously secrete vasoactive intestinal peptide (VIP). Watery diarrhea, hypokalemia and achlorhydria (WDHA) syndrome caused by VIP-producing tumors only rarely occurs in adult patients with non-pancreatic disease. In pediatric patients, it is extremely rare for a VIPoma to originate in the pancreas; instead, WDHA syndrome is usually associated with VIP-secreting neurogenic tumors involving the retroperitoneum or mediastinum. The majority of VIP secreting tumors in pediatric patients are represented by ganglioneuroblastomas or ganglioneuromas originating in the adrenal medulla or sympathetic neural crest. This syndrome of watery diarrhea associated with hypokalemia and achlorhydria was first described by Verner and Morrison, in 1958, and has been assumed to be due to hypersecretion of VIP. In children, as well as in adult patients, the most likely explanation for persistent secretory diarrhea may be an occult VIPoma. In conclusion, the physicians should be aware that there are some rare tumoral causes of chronic diarrhea, often under-diagnosed. If the diagnosis is not considered, extensive gastrointestinal investigations will be undertaken, delaying the diagnosis and avoidable morbidity will occur.


The Pathogen-Derived Aminoglycoside Resistance 16S rRNA Methyltransferase NpmA Possesses Dual m1A1408/m1G1408 Specificity.
Chemical modification of 16S rRNA can confer exceptionally high-level resistance to a diverse set of aminoglycoside antibiotics. Here, we show that the pathogen-derived enzyme NpmA possesses dual m(1)A1408/m(1)G1408 activity, an unexpected property apparently unique among the known aminoglycoside resistance 16S rRNA (m(1)A1408) methyltransferases. Although the biological significance of this activity remains to be determined, such mechanistic variation in enzymes acquired by pathogens has significant implications for development of inhibitors of these emerging resistance determinants.


The effect of a health literacy approach to counselling on the lifestyle of women with gestational diabetes: A clinical trial.
Background: Gestational diabetes is a common pregnancy disorder that affects the mother's and neonate's health. The present study was conducted to investigate the effect of a health literacy approach to counselling on the lifestyle of women with gestational diabetes. The present randomized controlled clinical trial was conducted in 2017 using a parallel design. The subjects included 84 eligible women presenting to Alborz and Kamali Hospitals, Karaj, Iran. Methods: Convenience sampling was first used to select the subjects. They were then assigned to an intervention or control group based on randomized blocks of four. Both groups attended counselling sessions. The mothers in the intervention group attended six sessions of counselling with a health literacy approach in addition to counselling on routine pregnancy care. The control group attended counselling sessions on safe pregnancy care and received a training package containing all the subjects discussed in the intervention group. The Lifestyle Questionnaire and the Iranian Health Literacy Questionnaire were completed by the mothers at the beginning and at the end of the sessions as well as three weeks after the sessions. The data obtained were analyzed in SPSS-19. Results: According to the study findings, the scores of lifestyle (P=0.8) and health literacy (P=0.423) showed no significant differences between the intervention and control groups before the intervention. Significant differences were, however, observed in the mean scores of lifestyle and health literacy between the two groups immediately and three weeks after the intervention. Comparing the means showed a higher increase in the mean scores in the intervention group (P<0.001). Conclusions: Providing counselling services by midwives can significantly help modify mothers' unhealthy lifestyle choices and increase their health literacy; therefore, reducing maternal and neonatal consequences, especially in high-risk pregnancies. Trial registration number: IRCT2017021427728N3 Trial registry: Iranian Registry of Clinical Trials Trial registration date: 5th April 2017.


Generation of skeletal myogenic progenitors from human pluripotent stem cells using non-viral delivery of minicircle DNA.
Currently, the most efficient and promising approach for generating large numbers of engraftable human skeletal myogenic progenitors from pluripotent stem cells requires the conditional in vitro overexpression of PAX7 using lentiviral vectors. Because a non-integrating approach would be preferable to eliminate or minimize the risk associated with random genomic integration, here we investigate whether transient expression of PAX7 using minicircle DNA would enable the generation of functional pluripotent stem cell-derived myogenic progenitors, equivalent to those generated by lentivirus. Our results demonstrate that upon multiple transfections, the minicircle approach allows for the scalable generation of myogenic progenitors and these undergo efficient terminal differentiation in vitro. However, transplantation of minicircle-generated myogenic progenitors resulted in limited engraftment. This is probably due to less efficient delivery and more transient PAX7 expression in these cultures since PAX7 downregulation is accompanied by high level of spontaneous differentiation. Thus, although the in vitro data shows that the minicircle approach could potentially replace the use of lentivirus, improvements in the transfection/expression system will be necessary before it will be a feasible strategy for the generation of myogenic progenitors for cell replacement therapy.


Identification of novel genetic factors underlying the host-pathogen interaction between barley (Hordeum vulgare L.) and powdery mildew (Blumeria graminis f. sp. hordei).
Powdery mildew is an important foliar disease of barley (Hordeum vulgare L.) caused by the biotrophic fungus Blumeria graminis f. sp. hordei (Bgh). The understanding of the resistance mechanism is essential for future resistance breeding. In particular, the identification of race-nonspecific resistance genes is important because of their regarded durability and broad-spectrum activity. We assessed the severity of powdery mildew infection on detached seedling leaves of 267 barley accessions using two poly-virulent isolates and performed a genome-wide association study exploiting 201 of these accessions. Two-hundred and fourteen markers, located on six barley chromosomes are associated with potential race-nonspecific Bgh resistance or susceptibility. Initial steps for the functional validation of four promising candidates were performed based on phenotype and transcription data. Specific candidate alleles were analyzed via transient gene silencing as well as transient overexpression. Microarray data of the four selected candidates indicate differential regulation of the transcription in response to Bgh infection. Based on our results, all four candidate genes seem to be involved in the responses to powdery mildew attack. In particular, the transient overexpression of specific alleles of two candidate genes, a potential arabinogalactan protein and the barley homolog of Arabidopsis thaliana's Light-Response Bric-a-Brac/-Tramtrack/-Broad Complex/-POxvirus and Zinc finger (AtLRB1) or AtLRB2, were top candidates of novel powdery mildew susceptibility genes.


Stigma in Cirrhotic Patients: A Qualitative Study.
Stigma is one of the main problems of patients suffering from cirrhosis, and it causes many challenges for the patients and their treatment. The present study aimed to discover and define the perceived stigma by cirrhotic patients. This qualitative study was conducted through a content analysis approach. The participants were 15 patients suffering from cirrhosis. Data were collected via semistructured, in-depth interviews and analyzed on the basis of methods described by Granheme and Landman. During data analysis, stigma was categorized into four categories and 13 subcategories: external representation of social stigma (others' avoidance behaviors, inadmissible tag, discriminative behaviors of treatment personnel, blaming behaviors), internal representation of social stigma (social ostracism, social isolation, curiosity to perceive people's perceptions), external representation of self-stigma (fear of disclosure of illness, threatening situation, difficult emotional relationships), and internal representation of self-stigma (condemned to suffer, self-punishment, self-alienation). Experiencing stigma is common among cirrhotic patients and may affect patients' coping with the illness and treatment. Thus, it is specifically important that treatment personnel know patients' perception, provide comprehensive support for these patients, and plan to enhance public awareness about the disease recommended.


[Three Candida auris Case Reports from Istanbul, Turkey].
Candida auris is a fungal pathogen that was first identified in 2009. Since its definition, it has spread globally and has caused life-threatening nosocomial infections. Increases in the number of immunocompromised individuals, empirical use of broad-spectrum antimicrobials and widespread use of catheterizations are the predisposing factors in the development of infection. There are problems for the identification of C.auris with the routine methods. In this case report, infections with C.auris, isolated for the first time from three patients in our hospital's intensive care units (ICU) between November 2020-January 2021, were presented. The first case was a 46-year-old male patient with laryngeal carcinoma who developed cardiopulmonary arrest during anesthesia induction in the tumor operation, and was followed up in the ICU. C.auris growth was detected in the blood and intravenous (IV) catheter tip cultures on the 66th day of admittance. Cure achieved on the 24th day under caspofungin treatment as no growth was determined. Second case was a 71-year-old female patient admitted to the emergency department with shortness of breath and general condition disorder that developed after COVID-19 infection and hospitalized in ICU with the diagnosis of pneumonia and acute renal failure. In the 16th day of admittance C.auris growth was detected in blood and from catheter tip cultures and the patient died in the 18th day. The third case was a 49-year-old male patient, followed up in ICU with the diagnosis of subarachnoid hemorrhage after he admitted to the emergency department with confusion. In the 35th day of admittance, 100000 CFU/ mL C auris growth was detected in urine culture. The patient was accepted as asymptomatic fungiuria and followed up in the ICU. It was determined that the three patients were intubated, had urinary and femoral venous catheters and were being followed under wide spectrum antibiotherapy when the growth of C.auris was detected. Isolates identified as C.auris by MALDI-TOF Microflex LT/SH Smart MS in the Medical Microbiology Laboratory were then confirmed by conventional methods and DNA sequencing in the National Mycology Reference Laboratory. Antifungal susceptibility tests were performed by broth microdilution method. Fluconazole MIC values were >256 mg/ml for all cases. Long-term survival in hospital environments, colonization on skin, resistance to disinfectants of C.auris, facilitate the spread of the fungi and resistance to antifungals lead to treatment failures. In this case report, it was aimed to draw attention to the infections with C.auris, its diagnosis and risk factors.


Assessment of depression-like behavior and anhedonia after repeated cycles of binge-like ethanol drinking in male C57BL/6J mice.
Psychological depression is frequently linked to alcohol abuse and even serves as key indicators of an alcohol use disorder (AUD). This relationship is supported by preclinical findings in which depression-like phenotypes develop in animals exposed to chronic intermittent ethanol vapor, a common preclinical model of alcohol dependence. However, the emergence of these maladaptive phenotypes following repeated binge-like ethanol drinking remains relatively unexplored. The purpose of this study was to evaluate depression-like behaviors associated with binge-like consumption in mice. Using the drinking-in-the-dark (DID) paradigm, we examined the impact of multiple binge-like cycles (1, 3, or 6) on depression-like behaviors in the forced swim test (FST) and sucrose preference as a test for anhedonia. We also assessed the effect of repeated binge cycles on the consumption of bitter and sweet tastants over a range of concentrations. Results indicated that binge-like ethanol drinking did not lead to depression-like behavior as repeated cycles of DID did not alter sucrose consumption or preference nor did it impact time spent immobile during the FST. Animals that experienced six cycles of DID showed increased quinine consumption and increased quinine preference, which may be indicative of an escalated preference for tastants that resemble the gustatory aspects of ethanol. Interestingly, an unexpected ~20% increase in hypermobility was observed after three cycles of binge-like ethanol drinking. Although the FST is most frequently used to model depression-like behavior, emerging evidence suggests that increased hypermobility during the FST could be indicative of an inability to cope in a stressful situation, suggesting that repeated ethanol exposure in the present experiment transiently enhances stress reactivity.


History of Childhood Maltreatment and College Academic Outcomes: Indirect Effects of Hot Execution Function.
College students who report a history of childhood maltreatment may be at risk for poor outcomes. In the current study, we conducted an exploratory analysis to examine potential models that statistically mediate associations between aspects of maltreatment and aspects of academic outcome, with a particular focus on executive functions (EF). Consistent with contemporary EF research, we distinguished between relatively "cool" EF tasks (i.e., performed in a context relatively free of emotional or motivational valence) and "hot" EF tasks that emphasize performance under more emotionally arousing conditions. Sixty-one male and female college undergraduates self-reported childhood maltreatment history (emotional abuse and neglect, physical abuse and neglect, and sexual abuse) on the Childhood Trauma Questionnaire (CTQ), and were given two EF measures: (1) Go-No-Go (GNG) test that included a Color Condition (cool); Neutral Face Condition (warm); and Emotion Face condition (hot), and (2) Iowa Gambling Task (IGT), a measure of risky decision making that reflects hot EF. Academic outcomes were: (1) grade point average (GPA: first-semester, cumulative, and semester concurrent with testing), and (2) Student Adaptation to College Questionnaire (SACQ). Correlational patterns suggested two EF scores as potential mediators: GNG reaction time (RT) in the Neutral Face condition, and IGT Block 2 adaptive responding. Indirect effects analyses indicated that IGT Block 2 adaptive responding has an indirect effect on the relationship between CTQ Total score and 1st semester GPA, and between CTQ Emotional Abuse and concurrent GPA. Regarding college adaptation, we identified a consistent indirect effect of GNG Neutral Face RT on the relationship between CTQ Emotional Neglect and SACQ total, academic, social, and personal-emotional adaption scores. Our results demonstrate that higher scores on a child maltreatment history self-report negatively predict college academic outcomes as assessed by GPA and by self-reported adaptation. Further, relatively "hot" EF task performance on the IGT and GNG tasks serves as a link between child maltreatment experiences and college achievement and adaptation, suggesting that hot EF skills may be a fruitful direction for future intervention efforts to improve academic outcomes for this population.


Statistical planning to address strongly correlated endpoints for inferential subgroups: An innovative approach for an illustrative clinical trial with complex multiplicity issues.
Multiplicity is an important statistical issue that arises in clinical trials when the efficacy of the test treatment is evaluated in multiple ways. The major concern for multiplicity is that uncontrolled multiple assessments lead to inflated family-wise Type I error, and they thereby undermine the integrity of the statistical inferences. Multiplicity comes from different sources, for example, making inferences either on the overall population or some pre-specified sub-populations, while multiple endpoints need to be evaluated for each population. Therefore, a sound statistical strategy that controls the family-wise Type I error rate in a strong sense, without excessive loss of power from over-control, is crucial for the success of the trial. For a recent phase III cardiovascular trial with such complex multiplicity, we illustrate the use of a closed testing strategy that begins with a global test; and subsequent testing only proceeds when the global test is rejected. Also, we discuss a simulation study based on this trial to compare the power of the illustrated closed testing strategy to some well-known alternative approaches. We found that this strategy can comprehensively meet most of the primary objectives of the trial effectively with reasonably high overall power.


Measurement of polyethylene wear in acetabular components inserted with and without cement. A randomized trial.
We measured the three-dimensional wear of polyethylene after total hip arthroplasty with a titanium metal-backed Mallory-Head prosthesis that was inserted with cement in sixty-nine patients (sixty-nine hips) and with a press-fit titanium metal-backed Mallory-Head prosthesis that was inserted without cement in seventy patients (seventy hips). A modular titanium femoral head was used in all of the hips. The patients in the present study were part of a larger double-blind randomized trial comparing the result of total hip arthroplasty performed with cement with that of the same procedure performed without cement in 250 patients. The criterion for inclusion in the study of polyethylene wear was a minimum duration of follow-up of four years, which was met by 148 patients. As adequate radiographs for digitization were not available for nine patients, 139 patients were included in the present study. The age of the patient, the postoperative Harris hip score, the diameter of the femoral head, the thickness of the liner in the polar region of the acetabular component, and the duration of follow-up were similar for the two groups. The mean rate of volumetric wear of the polyethylene was significantly greater in the prostheses that had been inserted without cement than in those that had been inserted with cement (155.1 cubic millimeters per year compared with 98.5 cubic millimeters per year; p = 0.000008). Thirty-four (49 per cent) of the seventy hips in which the prosthesis had been inserted without cement had evidence of osteolysis on radiographs, compared with twelve (17 per cent) of the sixty-nine hips in the other group (p = 0.0002). Osteolysis was associated with an increased rate of polyethylene wear only in the hips in which the prosthesis had been inserted without cement.


Newborn blood spot screening test using multiplexed real-time PCR to simultaneously screen for spinal muscular atrophy and severe combined immunodeficiency.
Spinal muscular atrophy (SMA) is a motor neuron disorder caused by the absence of a functional survival of motor neuron 1, telomeric (SMN1) gene. Type I SMA, a lethal disease of infancy, accounts for the majority of cases. Newborn blood spot screening (NBS) to detect severe combined immunodeficiency (SCID) has been implemented in public health laboratories in the last 5 years. SCID detection is based on real-time PCR assays to measure T-cell receptor excision circles (TREC), a byproduct of T-cell development. We modified a multiplexed real-time PCR TREC assay to simultaneously determine the presence or absence of the SMN1 gene from a dried blood spot (DBS) punch in a single reaction well. An SMN1 assay using a locked nucleic acid probe was initially developed with cell culture and umbilical cord blood (UCB) DNA extracts, and then integrated into the TREC assay. DBS punches were placed in 96-well arrays, washed, and amplified directly using reagents specific for TREC, a reference gene [ribonuclease P/MRP 30kDa subunit (RPP30)], and the SMN1 gene. The assay was tested on DBS made from UCB units and from peripheral blood samples of SMA-affected individuals and their family members. DBS made from SMA-affected individuals showed no SMN1-specific amplification, whereas DBS made from all unaffected carriers and UCB showed SMN1 amplification above a well-defined threshold. TREC and RPP30 content in all DBS were within the age-adjusted expected range. SMA caused by the absence of SMN1 can be detected from the same DBS punch used to screen newborns for SCID.


Novel Information Measures for Fermatean Fuzzy Sets and Their Applications to Pattern Recognition and Medical Diagnosis.
Fermatean fuzzy sets (FFSs) have piqued the interest of researchers in a wide range of domains. The striking framework of the FFS is keen to provide the larger preference domain for the modeling of ambiguous information deploying the degrees of membership and nonmembership. Furthermore, FFSs prevail over the theories of intuitionistic fuzzy sets and Pythagorean fuzzy sets owing to their broader space, adjustable parameter, flexible structure, and influential design. The information measures, being a significant part of the literature, are crucial and beneficial tools that are widely applied in decision-making, data mining, medical diagnosis, and pattern recognition. This paper aims to expand the literature on FFSs by proposing many innovative Fermatean fuzzy sets-based information measures, namely, distance measure, similarity measure, entropy measure, and inclusion measure. We investigate the relationship between distance, similarity, entropy, and inclusion measures for FFSs. Another achievement of this research is to establish a systematic transformation of information measures (distance measure, similarity measure, entropy measure, and inclusion measure) for the FFSs. To accomplish this aim, new formulae for information measures of FFSs have been presented. To demonstrate the validity of the measures, we employ them in pattern recognition, building materials, and medical diagnosis. Additionally, a comparison between traditional and novel similarity measures is described in terms of counter-intuitive cases. The findings demonstrate that the innovative information measures do not include any absurd cases.


Cardiac Nestin+ Cells Derived from Early Stage of Dilated Cardiomyopathy Enhanced the Survival of the Doxorubicin-Injured Cardiac Muscle HL-1 Cells.
Dilated cardiomyopathy (DCM), as one of the common cardiomyopathies, is a disease of the heart muscle; however, the etiology and pathogenesis of DCM were still poorly understood. Nestin has been reported a special marker of stem/progenitor cells in various tissues, and the tissue resident Nestin+ cells could promote the wound healing and tissue remodeling. However, it remains unclear whether Nestin+ cells participate in the protection of cardiomyocytes during the pathogenesis of DCM. Here the model of mice DCM was induced by doxorubicin (DOX) intraperitoneal injection and observed heart failure and ventricular enlargement via echocardiography and histologic analysis, respectively. During DCM pathogenesis, the number of Nestin+ cells showed a significant peak on day 6 after DOX treatment, which then gradually decreases to lower than normal levels after day 30 in the total population of the heart. Furthermore, we found that the isolated increased heart-derived Nestin+ cells are mesenchymal property and could protect DOX-induced HL-1 cells toxicity in vitro by promoting their proliferation and inhibiting their apoptosis. Collectively, our results showed that Nestin+ cells increased during DCM pathogenesis and played an important role in protecting against the DOX-induced HL-1 cells loss via regulating proliferation and apoptosis. Thus, the loss of Nestin+ cells might be an etiology to DCM pathogenesis, and these cells could be a promising candidate cell source for study and treatment of DCM patients.


Waiting time at a fast-track diagnostic clinic.
Purpose - Guidelines stating maximum waiting times fail to take cancer patients' expectations into account. Therefore, the purpose of this paper is to assess patients' expectations and experiences with their waiting time at a fast-track clinic. Design/methodology/approach - Patients were selected using a purposeful sampling strategy and were interviewed four times: before the visit; one day after; two weeks after the visit; and one week after starting treatment. Interviews were audiotaped and independently coded by two researchers. Findings - All patients (n=9) preferred a short waiting time before the first visit; they feared that their disease would spread and believed that cancer warrants priority treatment. Six patients experienced the waiting time as short, one had no expectations and two felt they waited longer than expected; three patients changed this evaluation during the study. Six patients received treatment - four preferred to wait before treatment and two wanted to start treatment immediately. Reasons to wait included putting one's affairs in order, or needing to adjust to the diagnosis. Practical implications - Cancer patients prefer a short waiting time before the first visit but have different expectations and needs regarding waiting time before treatment. Ideally, their expectations are managed by their treating physician to match waiting time reality. Originality/value - This is the first study to assess cancer patients' waiting time experiences and how these experiences change over time. This study paves the way for establishing a framework to better assess patient satisfaction with oncology care waiting time. An important aspect, is managing patients' expectations.


Reaching endpoints for lymphatic filariasis elimination- results from mass drug administration and nocturnal blood surveys, South Gujarat, India.
Following the World Health Assembly resolution on Elimination of lymphatic filariasis (ELF) as a public health problem by the year 2020, a Global Program (GPELF) was launched in 1997 to help endemic countries to initiate national programs. The current strategy to interrupt transmission of LF, is administration of once-yearly, single-dose, two-drug regimen (Albendazole with Diethylcarbamazine (DEC) to be used in endemic areas with the goal of reaching 65% epidemiological coverage for 4-6 years. We report findings of independent assessment from year 2010 to 2015 for last six rounds, after initial five rounds of Mass Drug Administration (MDA) since 2005 for ELF in endemic area of Gujarat. Independent assessment of MDA was performed to find coverage and compliance indicators, reasons for non-coverage and non-compliance in five Implementation Units (IUs). Pre, during and post MDA evaluations were done in three phases. The impact of MDA was measured by microfilaraemia survey. A total of eight sites, four random and four fixed sentinel sites were selected to calculate microfilaria rate (MF) per IUs per year. In years 2010 to 2015, we report results from 125,936 nocturnal blood smears and 17551 population in 120 selected clusters. Four clusters were selected per year in each of the five IUs for assessment of MDA round. Post MDA survey showed drug coverage between 81%-88% and epidemiological coverage 77%-89% across years. Main reasons for non-coverage were drug administrator related (the team did not visit or missed people) while non-compliance was population related (fear of side effects, sickness, people forgot or absent). During MDA findings show that the directly observed consumption is considerably improved from 58% in 2010 to 82% in 2015. The knowledge about benefits of drug provided also increased from 59% to 90% over the years. The current MF rate is less than one in all IUs with an overall 68% percent decrease from baseline year 2005 to year 2015. The average MF rate of Gujarat is 0.44 for year 2015. The findings show that achieving adequate epidemiological and drug coverage is possible by actual field level operation of the program in large endemic areas. The results and feedback from independent assessment, performed regularly, could guide the policymakers and program managers for mid-term corrections and to frame strategies to enhance program. Monitoring of coverage and impact indicator together informs decisions for reaching end-point of MDA. The impact indicator- microfilaria rate in all IUs of South Gujarat Region has reached and remained less than one percent signaling end-points of MDA. Post MDA stringent monitoring in form of TAS is recommended to keep vigil on maintenance of elimination achieved.


Comprehensive Scheme for Identifying Defects in Solid-State Quantum Systems.
A solid-state quantum emitter is a crucial component for optical quantum technologies, ideally with a compatible wavelength for efficient coupling to other components in a quantum network. It is essential to understand fluorescent defects that lead to specific emitters. In this Letter, we employ density functional theory (DFT) to demonstrate the calculations of the complete optical fingerprints of quantum emitters in hexagonal boron nitride. Our results suggest that instead of comparing a single optical property, like the zero-phonon line energy, multiple properties should be used when comparing simulations to the experiment. Moreover, we apply this approach to predict the suitability of using the emitters in specific quantum applications. We therefore apply DFT calculations to identify quantum emitters with a lower risk of misassignments and a way to design optical quantum systems. Hence, we provide a recipe for classification and generation of universal quantum emitters in future hybrid quantum networks.


The sex difference of plasma homovanillic acid is unaffected by cross-sex hormone administration in transsexual subjects.
There is a close relationship between the brain and the endocrine system. The brain expresses receptors for sex steroids and is capable of metabolizing these hormones. We explored (1) sex differences in homovanillic acid (HVA), a metabolite of the neurotransmitter dopamine, and (2) the effects of cross-sex steroid administration in transsexual subjects. First, we compared plasma HVA levels between 38 male and 34 female healthy volunteers (not using hormone replacement therapy) of a mean age of 72 years (range 65-84 years). Secondly, we measured plasma HVA levels in 15 male-to-female transsexuals treated with 100 microg ethinyl estradiol/day and 100 mg cyproterone acetate/day for 4 months, and in 17 female-to-male transsexuals treated with testosterone esters (250 mg/2 weeks i.m. for 4 months). Plasma HVA levels were lower in elderly men than in elderly postmenopausal women (geometric mean 25.4 nmol/l (percentile (P)10 4.9; P90 69.8) vs 39.0 nmol/l (19.0; 76.1); P=0.027). In transsexuals before cross-sex hormone administration, genetic males also had lower plasma levels of HVA than genetic females (geometric mean 14.8 nmol/l (P10 7.0; P90 35.0) vs 34.3 nmol/l (21.8; 61.4); P<0.001). Cross-sex hormone administration did not affect plasma HVA in either group (P>0.5). The pretreatment sex difference in plasma HVA was unaffected after 4 months of cross-sex hormone administration (P=0.003). The sex difference in plasma HVA was not reversed by cross-sex hormone administration in transsexuals, and was also preserved in elderly subjects. This indicated that differences in dopamine gene expression were largely unaffected by exposure to sex hormone levels in adulthood, but must rather be explained by a sex difference in genetic factors or by the organizing effects of sex hormones during early development.


Bilateral interaction between cord blood-derived human neural stem cells and organotypic rat hippocampal culture.
The umbilical cord blood-derived neural stem/progenitor cells (HUCB-NSCs) potentially represent a rich source of transplantable material for treatment of a wide range of neurological diseases. Although, recently reported effects of their implementation in animal models of brain pathology are still controversial. As a simplified alternative to in vivo transplantation in this work we have applied a long-term organotypic rat hippocampal slice culture (OHC) as a recipient tissue to study bilateral graft/host cells interactions ex vivo. This type of culture can be considered as a kind of reductionistic model of brain transplantation where direct influence of systemic immunological responses to transplanted human cells would be excluded. The transplantation material derived from a HUCB-NSC line developed and characterized in our laboratory and delivered to the slices either as a single-cell suspension or after formation of typical neurospheres in serum-free medium in vitro (N-HUCBs). Experiments were focused on space-temporal context of cell transplantation in relation to their ability to ingrown, migrate, and differentiate within the slice cytoarchitecture. We gain evidences that these responses are strictly dependent on the engraftment site and that cell movement reflects typical routes used for migratory neuroblasts in vivo. The cells implanted at the second week of slice cultivation ingrown readily and deeply into host cytoarchitecture then matured to the level never observed in our transplantation animal models in vivo. Importantly, transplanted neurospheres, in addition to yield exogenous migratory cells to the host tissue can locally inhibit astrocytosis and promote outgrow of DCX-reactive neuroblasts in the surrounding OHC tissue.


Secretory phospholipase A2 cleavage of intravasated bone marrow primes human neutrophils.
Recent clinical reports suggest that early femoral intramedullary rod (IMR) fixation in patients with multiple injuries increases the risk of adult respiratory distress syndrome (ARDS). We have shown that lipid-mediated neutrophil (PMN) priming and elevated circulating levels of secretory phospholipase A2 (sPLA2) within the first 24 hours after injury correlate with the development of ARDS. We thus hypothesized that circulating lipid products, generated by sPLA2 cleavage of intravasated bone marrow, prime PMNs for enhanced superoxide anion (O2-) production. Isolated PMNs from healthy volunteers were incubated for 5 minutes with buffer or sPLA2-lysed bone marrow (100 U/mL) collected from trauma patients. After formyl-methionyleucylphenylalanine (fMLP) activation, O2- production was quantified by the superoxide dismutase-inhibitable reduction of cytochrome c. Blood samples were also drawn from five injured patients before and 24 hours after femoral IMR fixation. PMNs were isolated and assessed for in vivo priming. PMNs incubated with sPLA2-lysed bone marrow were primed for more than 3.5 times greater fMLP-induced O2- production. Furthermore, in patients with femoral fractures, PMN O2- release in response to fMLP after IMR fixation was more than 2.5 times higher than before fixation. Collectively, the findings suggest that bone marrow released from acute fracture sites may become a lipid substrate for the elevated sPLA2 levels found in injured patients. The resultant priming of PMNs may thus render the injured patient at risk for ARDS. Although clearly hypothetical at present, we submit that these observations warrant further investigation because of their clinical implications.


Saccular aneurysm of the distal anterior choroidal artery--case report.
The authors report a case of a distal anterior choroidal artery aneurysm in a 75-year-old female who presented with nausea, vomiting, and severe headache. Computed tomographic (CT) scans revealed a hematoma in the right lateral ventricle and a subarachnoid hemorrhage in the right parasellar-Sylvian cistern. Cerebral angiography showed a saccular aneurysm at the right distal anterior choroidal artery. The authors intended to operate at the chronic stage, and carried out conservative management. After 1 month her condition suddenly worsened and she died, although a CT scan showed no remarkable changes. At autopsy, a pulmonary artery thrombosis was considered the cause of death. The aneurysm was identified in the temporal horn of the right lateral ventricle, and was a true aneurysm.


Identification and bioinformatic analysis of a putative calcium-dependent protein kinase (CDPK6) from Toxoplasma gondii.
Toxoplasma gondii is recognized as an opportunistic human pathogen with a worldwide distribution. Development of effective vaccines is considered the only ideal way to control T. gondii infection. However, only one live vaccine is commercially available for use in sheep and goats. Therefore, the identification of more effective antigenic proteins is very important. In this study, we identified a novel putative calcium-dependent protein kinase of T. gondii, TgCDPK6, and further analyzed its potential antigenicity using a bioinformatic approach. The physical and chemical characteristics, transmembrane domain, epitopes, advanced structure, and functional sites of TgCDPK6 were predicted by multiple bioinformatic approaches. Twenty-six post-translational modification sites were identified in the protein. The secondary structure showed that 58.35% amino acids of TgCDPK6 are exposed to the solvent interface, and the high hydrophilic domains were distributed in amino acid positions 21-59, 68-81, 156-205, 245-271, 280-294, 297-324, 334-356, 367-393, 474-498, and 543-553. The advanced structure of TgCDPK6 was developed by a homology modeling method and was validated by PROCHECK, which showed that most amino acid residues were in the most favored regions. Using these analyses, 10 potential epitopes were predicted. The results indicated that TgCDPK6 could be a vaccine candidate antigen against T. gondii.


Communication: Proper treatment of classically forbidden electronic transitions significantly improves detailed balance in surface hopping.
Surface hopping is the most popular method for nonadiabatic molecular dynamics. Many have reported that it does not rigorously attain detailed balance at thermal equilibrium, but does so approximately. We show that convergence to the Boltzmann populations is significantly improved when the nuclear velocity is reversed after a classically forbidden hop. The proposed prescription significantly reduces the total number of classically forbidden hops encountered along a trajectory, suggesting that some randomization in nuclear velocity is needed when classically forbidden hops constitute a large fraction of attempted hops. Our results are verified computationally using two- and three-level quantum subsystems, coupled to a classical bath undergoing Langevin dynamics.


Synchronization in monkey visual cortex analyzed with an information-theoretic measure.
We apply an information-theoretic measure for phase synchrony to local field potentials (LFPs) [corrected] recorded with a multi-electrode array implanted in area V4 of the monkey visual cortex. We show for the first time statistically significant stimulus-dependent synchrony of the visual cortical LFPs and this during different, short time intervals of the response. Furthermore, we could compute waves of synchronous activity over the array and correlate their timing with the stimulus-dependent difference in synchrony [corrected]


Identification of novel regulatory factor X (RFX) target genes by comparative genomics in Drosophila species.
Regulatory factor X (RFX) transcription factors play a key role in ciliary assembly in nematode, Drosophila and mouse. Using the tremendous advantages of comparative genomics in closely related species, we identified novel genes regulated by dRFX in Drosophila. We first demonstrate that a subset of known ciliary genes in Caenorhabditis elegans and Drosophila are regulated by dRFX and have a conserved RFX binding site (X-box) in their promoters in two highly divergent Drosophila species. We then designed an X-box consensus sequence and carried out a genome wide computer screen to identify novel genes under RFX control. We found 412 genes that share a conserved X-box upstream of the ATG in both species, with 83 genes presenting a more restricted consensus. We analyzed 25 of these 83 genes, 16 of which are indeed RFX target genes. Two of them have never been described as involved in ciliogenesis. In addition, reporter construct expression analysis revealed that three of the identified genes encode proteins specifically localized in ciliated endings of Drosophila sensory neurons. Our X-box search strategy led to the identification of novel RFX target genes in Drosophila that are involved in sensory ciliogenesis. We also established a highly valuable Drosophila cilia and basal body dataset. These results demonstrate the accuracy of the X-box screen and will be useful for the identification of candidate genes for human ciliopathies, as several human homologs of RFX target genes are known to be involved in diseases, such as Bardet-Biedl syndrome.


Transversal fixation of restorations in combination with the Octa abutment of the ITI Dental Implant System.
In aesthetically demanding locations of the dentition, the replacement of a single tooth by means of an oral implant is often difficult because of technical limitations of the abutments systems used. The transversal Fixation System in combination with the Octa abutment of the ITI Dental Implant System presents a novel development to overcome these limitations. The report describes the engineering and design of this technical development.


Potential of CD34 in the regulation of symmetrical and asymmetrical divisions by hematopoietic progenitor cells.
The control of symmetric and asymmetric division in the hematopoietic stem/progenitor cell population is critically important for the regulation of blood cell production. Asymmetric divisions depend on cell polarization, which may be conferred by location and/or interaction with neighboring cells. In this study, we sought evidence for polarization in CD34+ cells, which interact by binding to one another. In these cells, surface molecules became redistributed by mechanisms that included transport by lipid rafts, and the interacting cells were able to communicate via gap junctions. These changes were accompanied by modulation of cell cycle regulating proteins (p16(Ink4a), p27(kip1), cyclins D, and the retinoblastoma pathway proteins) and a reduction in progenitor cell proliferation in vitro. These results are consistent with an increase in asymmetric cell division kinetics. Accordingly, we found that interaction between CD34+ cells influenced the plane of cell division in a way that suggests unequal sharing of Notch-1 between daughter cell progeny. We conclude that interaction between CD34+ cells may coordinate cell function and participate in the control of hematopoietic stem/progenitor cell division kinetics.


Febrile urinary tract infection in the emergency room.
To review the recent advances in the diagnostic and therapeutic approach to adults presenting with febrile urinary tract infection (UTI) in the emergency department (ED). Recent research suggests overdiagnosis and therefore overtreatment of UTI in the ED, especially in the elderly. Antimicrobial pretreatment, an indwelling catheter, and malignancy are independent risk factors for bacteremia with uropathogens that cannot be cultured from urine. A simple clinical prediction rule can predict clinically relevant radiologic findings in patients with invasive UTI. Procalcitonin is a marker for bacteremia; pro-adrenomedullin predicts a complicated course and 30-day mortality in complicated UTI. Several reports have identified the risk factors for resistant uropathogens in community-acquired febrile UTI. Adherence to the guidelines and early culture-guided intravenous-to-oral switch reduces the length of hospitalization. An effective strategy is needed to improve the diagnosis of UTIs in acute care. Further research regarding biomarker-guided triage might improve the management of patients with febrile UTI. Future efforts should be directed toward the improvement of adherence to UTI treatment guidelines.


What drives the number of high-risk human papillomavirus types in the anal canal in HIV-positive men who have sex with men?
We estimated the effect of sexual behavior, age, and immunodeficiency on the number of high-risk human papillomavirus (HR-HPV) types in the anal canal among human immunodeficiency virus-positive men who have sex with men (MSM). Anal samples were genotyped with the Linear Array HPV Genotyping Test, and risk factors were investigated with Poisson regression. Of 586 MSM, 69% were Spanish, and 25.6% were Latin American; the median age was 34.9 years (interquartile range [IQR], 30.1-40.8). The median number of recent sex partners was 6 (IQR, 2-24 sex partners), and the median CD4(+) T-cell count was 531.5 cells/mm(3) (IQR, 403-701 cells/mm(3)). The prevalence of any and multiple HR-HPV infections was 83.4% and 60.5%, respectively. The most common types were HPV-16 (42%), HPV-51 (24%), HPV-39 (23.7%), and HPV-59 (23.5%). Age had a statistically significant, nonlinear association with the number of types, with the highest number detected around 35 years of age (P < .001). The number of recent sex partners had a statistically significant, fairly linear association on the log scale (P = .033). The high prevalence of HR-HPV types is associated with recent sexual behavior and age.


Radiotherapy for postoperative vaginal recurrences of cervical squamous cell carcinoma: analysis of dosing and prognosis.
Squamous cell carcinoma (SCC) is the most common type of vaginal recurrence in cervical cancer patients, and the role of salvage radiotherapy on these patients remains unclear. This study aimed to investigate the efficacy of salvage radiotherapy for vaginal recurrence of SCC in patients who previously underwent surgery and to explore prognostic factors associated with survival. Ninety-seven patients with histologically proven SCC who were treated for vaginal recurrence at Peking Union Medical College Hospital were identified. All patients had previously undergone surgery and received salvage radiotherapy. Factors predictive of overall survival (OS), progression-free survival (PFS), and local control (LC) were investigated. The median follow-up time was 42.5 months. The estimated 5-year OS, PFS, and LC rates were 84%, 79%, and 91%. On multivariate analysis, inguinal lymph node metastasis was significantly associated with poor OS; a tumour size ≤4 cm was associated with longer PFS (p < 0.05); the recurrence pattern was an independent predictor of LC (p < 0.05). In the 45 patients with recurrences that were paravaginal or invasive of surrounding organs, biologically equivalent doses in 2 Gy fractions of ≥72.6 Gy were independently predictive of longer LC (p < 0.05). RT is an effective treatment for postoperative vaginal recurrence in patients with cervical SCC. For patients with extravaginal recurrence, a salvage dose of ≥72.6 Gy appears to be optimal.Impact statementWhat is already known on this subject? Radiotherapy plays a critical role in treating recurrent cervical cancer, but the effectiveness of RT for vaginal recurrence in patients who previously underwent surgery remains limited. Few studies have focussed on the effect of RT dose on patient survival.What do the results of this study add? This study investigated the efficacy of RT in patients with cervical squamous cell carcinoma who experienced postoperative recurrence. Lymph node metastasis, tumour size and recurrence pattern were significantly associated with survival. Moreover, an EQD2 ≥ 72.6 Gy was independently predictive of longer LC.What are the implications of these findings for clinical practice and/or further research? RT is an effective treatment for postoperative vaginal recurrence in patients with cervical squamous cell carcinoma. For patients with extravaginal recurrence, a salvage dose of ≥72.6 Gy appears to be optimal.


Cognitive reserve does not support the retrieval of well-known proper names in older people.
To assess the role of cognitive reserve, age, gender and brain structure in proper name retrieval in advanced age. Performance in 2 naming tasks (asking for proper names or common names) and 2 memory tasks was assessed. In separate hierarchical regressions, we evaluated whether retrieval was predicted by gray matter thickness or volume in selected structures (Model 1) and whether the addition of age and gender (Model 2) or of education (Model 3) explained significantly more variance. Participants were healthy persons (ages 70-90 years). Out of 91 individuals, 18 were excluded after inspection of magnetic resonance imaging scans showing relevant white matter changes. The remaining 73 individuals (47 women) showed good cognitive abilities. Age was a significant predictor for the retrieval of well-known proper names, whereas selected gray matter measures and education had no significant effect. In contrast, education was predictive of common names retrieval and performance in the memory tasks. Gray matter measures predicted performance in the 2 memory tasks. Cognitive reserve has a differential effect on cognitive abilities in advances age. Education did not support the retrieval of well-known proper names but positively affected the retrieval of common names and performance in memory tasks. Cognitive reserve has to be considered in neuropsychological diagnostic procedures. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Clustering of DNA sequences in human promoters.
We have determined the distribution of each of the 65,536 DNA sequences that are eight bases long (8-mer) in a set of 13,010 human genomic promoter sequences aligned relative to the putative transcription start site (TSS). A limited number of 8-mers have peaks in their distribution (cluster), and most cluster within 100 bp of the TSS. The 156 DNA sequences exhibiting the greatest statistically significant clustering near the TSS can be placed into nine groups of related sequences. Each group is defined by a consensus sequence, and seven of these consensus sequences are known binding sites for the transcription factors (TFs) SP1, NF-Y, ETS, CREB, TBP, USF, and NRF-1. One sequence, which we named Clus1, is not a known TF binding site. The ninth sequence group is composed of the strand-specific Kozak sequence that clusters downstream of the TSS. An examination of the co-occurrence of these TF consensus sequences indicates a positive correlation for most of them except for sequences bound by TBP (the TATA box). Human mRNA expression data from 29 tissues indicate that the ETS, NRF-1, and Clus1 sequences that cluster are predominantly found in the promoters of housekeeping genes (e.g., ribosomal genes). In contrast, TATA is more abundant in the promoters of tissue-specific genes. This analysis identified eight DNA sequences in 5082 promoters that we suggest are important for regulating gene expression.


Potential changes in rat spermatogenesis and sperm parameters after inhalation of Boswellia papyrifera and Boswellia carterii incense.
In this study the effect of Boswellia papyrifera (B. papyrifera) and Boswellia carterii (B. carterii) smoke exposure on spermatogenesis and sperm parameters in male albino rats was investigated. Rats (n = 11) were exposed daily in smoking chambers to smoke emanated by burning 4 g each of either B. papyrifera or B. carterii for 48 days. At the end of exposure duration rats were killed, and the testes were excised and analysed for histopathological and ultrastructural changes. Sperm analysis including total sperm count, motility, velocity and relative percentage of abnormal sperms were recorded. Rats exposed to B. papyrifera and B. carterii showed significant disturbances in spermatogenetic patterns and changes in sperm kinetics compared to unexposed rats. Atrophied seminiferous tubules with dynamic changes were also noticed. The boundaries of intercellular and intracellular vacuoles were seen in the Sertoli cells. Furthermore, in spermatids acrosomal vesicles were not fully formed. Degenerating spermatids were devoid of their nuclear membrane with electron dense matrix and vacuolization. Structural changes in Leydig cells were observed. Sperm analysis in exposed rats exhibited significant decrease in the sperm count, motility, speed and an increase in sperm anomalies when compare to controls. These findings demonstrate that the B. papyrifera and B. carterii smoke affects the process of spermatogenesis and sperm parameters and indicate the detrimental effects of these incense materials on human reproductive system.


A case report of Linguatula serrata in human throat from Tehran, central Iran.
A case of linguatulosis due to Linuatula serrata, a zoonotic pentastomid parasite in throat of a 28 years old woman from Tehran is described. After removal of the parasites the patient was discharged without any further complaining.


[Introductional results of a mortality study in 471 ex-exposed workers to PCBs].
This study concerned a group of ex-workers (372 males and 99 females) from a firm situated in Bergamo (Italy) that ceased its activity at the beginning of the Nineties. From an introductory analysis of the results, we found out that there isn't excess in the death-rate for liver and bile ducts cancers among the males of this group. Among them, for what concerns the other tumoral pathologies, such as leukaemia and stomach tumors, the information allowed to verify an excess of mortality. However, this increase hasn't result statistically significant. On the contrary, it came out that there is an excess of risk for intestine tumors: standardized death-rate of 2.58. In accordance with the information collected, for the future it will be necessary to carefully examine the research in order to verify the existence of a direct connection to the exposure at PCB and study the incidence (not only for mortality) of these neoplasms.


Radiological assessment of necrosis in glioblastoma: variability and prognostic value.
In a previous study, we found that the extent of necrosis was the only radiological feature which correlated significantly with survival in patients with glioblastoma. The aim of this paper was to evaluate the variability and prognostic value of the extent of the necrotic area as seen on contrast-enhanced MRI and CT in a larger series. We studied 72 patients who underwent surgical removal of supratentorial glioblastomas and had CT and/or MRI with contrast medium before surgery; 38, all undergoing the same treatment (surgery plus radiotherapy), were followed clinically. Necrosis within the tumour varied greatly, ranging from none (only 1 case) to involvement of 76% of the tumour. Survival data in the subgroup suggested that only patients with a small area of necrosis (less than 35% of the tumour) had a significantly longer survival time. When necrosis involved more than 35% of the mass, patients had a shorter survival time, without any further correlation with the extent of necrosis.


Bulge loops used to measure the helical twist of RNA in solution.
Bulge loops are commonly found in helical segments of cellular RNAs. When incorporated into long double-stranded RNAs, they may introduce points of flexibility or permanent bend that can be detected by the altered electrophoretic gel mobility of the RNA. We find that a single An or Un bulge loop near the middle of a long RNA helix significantly retards the RNA during polyacrylamide gel electrophoresis if n greater than or equal to 2. The mobility of an RNA containing two A2 bulges various periodically with the number of base pairs between the bulges. We interpret this to mean that A2 bulges varies periodically with the number of base pairs between the bulges. We interpret this to mean that Z2 bulges form torsionally stiff bends in the helix; the gel mobility reaches a minimum when the total helical twist between the bulges rotates the arms of the molecule into a cis conformation. The gel mobilities are proportional to the predicted end-to-end distance of the RNA if the average RNA helical repeat is 11.8 +/- 0.2 bp/turn and there is no helical twist (3 +/- 9 degrees) associated with the bulge (data obtained in 0.15 M Na+). Other sizes and sequences of bulges have very different effects on RNA helix conformation and flexibility. U2 bulges bend the helix to a much smaller degree than A2 bulges, while longer A or U bulge sequences probably allow bends of 90 degrees or more; all of these may be fairly flexible joints.(ABSTRACT TRUNCATED AT 250 WORDS)


Functional Outcomes in Survivors of Pediatric Sepsis: A Scoping Review and Discussion of Implications for Low- and Middle-Income Countries.
Pediatric sepsis is an important cause of mortality and morbidity in low- and middle-income countries (LMIC), where there is a huge burden of infectious diseases. Despite shortage of resources, adapting protocol-based care has reduced sepsis-related deaths but survivors of pediatric sepsis are at risk of poor functional outcomes. To perform a scoping review of the literature on functional outcomes of pediatric sepsis survivors after discharge from the intensive care unit (ICU) and discuss the implications for patients in LMICs. The outcomes include prevalence of survival with reduced functional outcomes or quality of life (QoL) and changes over time during follow-up or recovery, and these outcomes were compared with other groups of children. We searched major medical electronic databases for relevant literature from January 2005 until November 2021, including Medline (via PubMed), Embase, CINAHL, and Google Scholar databases. We included observational studies and follow-up data from clinical trials involving children/adolescents (≤18 years) who were admitted to pediatric intensive care unit (PICU) and got discharged finally. Major focus was on survivors of sepsis in LMIC. We followed PRISMA guidelines for scoping reviews (PRISM-ScR). We included eight papers reporting data of functional outcomes in 2,915 children (males = 53%, and comorbidity present in 56.6%). All included studies were either a prospective or retrospective cohort study. Studies were classified as Level II evidence. Disabilities affecting physical, cognitive, psychological, and social function were reported in children following discharge. Overall disability reported ranged between 23 and 50% at hospital discharge or 28 days. Residual disability was reported at 1, 3, 6, and 12 months of follow-up with an overall improving trend. Failure to recover from a baseline HRQL on follow-up was seen in one-third of survivors. Organ dysfunction scores such as pSOFA, PeLOD, vasoactive inotrope score, neurological events, immunocompromised status, need for CPR, and ECMO were associated with poor functional outcome. The research on functional outcomes in pediatric sepsis survivors is scarce in LMIC. Measuring baseline and follow-up functional status, low-cost interventions to improve management of sepsis, and multidisciplinary teams to identify and treat disabilities may improve functional outcomes.


[Study of diffusion weighted imaging in combination with conventional MRI signs for inflammation activity of chronic hepatitis B].
Objective: To study the correlation between ADC values of diffusion weighted imaging (DWI) and the pathological grading in inflammation activity of chronic hepatitis B, and combined with conventional MRI features to predict the diagnosis effectiveness. Methods: A total of 142 cases of patients with chronic hepatitis B were selected as inflammatory group in 302 Hospital of PLA from January 2014 to December 2015, while 20 cases of healthy subjects without history of liver disease were chosen as control group.All patients underwent MR plain scan and dynamic contrast enhancement and DWI examinations (b=0, 800 s/mm(2)) for liver, and were performed liver biopsy within two days.According to the degree of inflammation activity (G), the inflammation group was divided into G1, G2 and G3-4 level.The apparent diffusion coefficient (ADC) value, and the MRI features of each group were analyzed. Results: The ADC values showed statistical difference (F=8.392, P<0.01) within inflammation group of chronic hepatitis B from different pathologic grading, and there was significant negative correlation between ADC values and liver inflammation activity grading (r=-0.613, P<0.01). The ADC value of inflammation group and control group was (1.31±0.16), (1.12±0.15)×10(-3) mm(2)/s, the difference was statistically significant (P<0.05). The ADC value of G1, G2 and G3-4 level was (1.22±0.12), (1.05±0.12), (0.98±0.10)×10(-3) mm(2)/s respectively, and there was statistical difference (P<0.05) between G1 and G2, G1 and G3-4. The receiver operating characteristic (ROC) curve in diagnosis of equal and above G2 level showed the area under the curve (AUC) was 0.880, the sensitivity and the specificity was 82.4% and 76.8% respectively, the diagnostic cut-off value was 1.09×10(-3) mm(2)/s.Besides, the detection rate of portal around its orbit and gallbladder wall edema in inflammation group had statistical difference (P<0.05), and there was no statistical difference in the detection rate of abnormal liver arterial enhancement, hilus lymph node increases and ascites in inflammation group(P>0.05). The ROC in diagnosis of equal and above G2 level by ADC values combined with the MRI characteristic signs showed AUC was 0.938, the sensitivity and the specificity was 88.4% and 88.9% respectively. Conclusions: ADC values can predict the inflammation activity of chronic hepatitis B with quantitatively and non-invasively.Combining with characteristic MRI signs, ADC values can improve the diagnosis efficiency.


Pharmacogenomics of chloroquine and hydroxychloroquine: current evidence and future implications.
As substrates of CYP2C8, CYP3A4/5 and CYP2D6, chloroquine's (CQ) and hydroxychloroquine's (HCQ) efficacy and safety may be affected by variants in the genes encoding these enzymes. This paper aims to assimilate the current evidence on the pharmacogenomics of CQ/HCQ and to identify risk phenotypes affecting the safety or efficacy of these drugs. It has been found that some CYP3A5, CYP2D6 and CYP2C8 genetic variants may affect the safety or effectiveness of CQ/HCQ. The phenotypes predictively representing ultra-rapid and poor metabolizers have been considered high-risk phenotypes. After considering these high-risk phenotypes in different ethnic groups, it is predicted that a considerable proportion of patients taking CQ/HCQ may be at risk of either therapeutic failure or severe toxicities.


Primary thyroid-like low-grade nasopharyngeal papillary adenocarcinoma: A case report and literature review.
Primary thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (TL-LGNPPA) is an extremely rare malignant nasopharyngeal tumor with features resembling papillary thyroid carcinoma including nuclear positive expression of thyroid transcription factor-1 (TTF-1). A 64-year-old male presented with nasal bleeding and a foreign body sensation of the nasopharynx. Laryngoscopy revealed a 2.0-cm broad-based mass with a smooth surface on the posterior wall of the nasopharynx. A biopsy was obtained. Histopathologic examination demonstrated tumor cells arranged in both papillary and glandular architecture. The tumor cells express nuclear immunoreactivity for TTF-1. The diagnosis of TL-LGNPPA was made. After the patient was diagnosed with TL-LGNPPA, he underwent complete surgical resection. There was no recurrence or evidence of metastatic disease at the 12-month follow-up. TL-LGNPPA is easy to misdiagnose as metastatic papillary thyroid carcinoma or other relative primary adenocarcinomas. It is important to have a broad differential diagnosis and know the key features of each entity because the prognosis and clinical treatment of each may differ.


A Wilms tumor cell line, HFWT, can greatly stimulate proliferation of CD56+ human natural killer cells and their novel precursors in blood mononuclear cells.
A Wilms tumor cell line, HFWT, selectively stimulates expansion of natural killer (NK) cells from human peripheral blood mononuclear cells (PBMC). In this study, we attempted to identify NK precursors in PBMC or in cord blood mononuclear cells (CBMC) that preferentially respond to feeder HFWT cells. Human NK cells or candidate precursor cells were fractionated from PBMC or CBMC by magnetic antibody cell sorting or by flow cytometry and applied to limiting dilution analysis to determine the proportion of NK/NK precursor cells, which are able to proliferate on irradiated HFWT cells. NK and NK precursor cells were cultured in medium containing interleukin-2 (IL-2). Expansion of NK cells from both resting NK cells and NK precursor cells was examined using proliferation from single cells, expression of NK cell markers, and cytotoxic activity. In the limiting dilution analysis, NK cells expanded on irradiated HFWT cells not only from CD3-CD56bright and CD3-CD56dim NK cells, but also from CD16+/-CD122+ cells in the lineage-negative (Lin-, CD3-CD14-CD19-CD56-) cell fraction. The feeder HFWT cells stimulated Lin-CD122+ cell proliferation more strongly than feeder cells from the well-known human NK target cell line K562. CBMC contained significantly higher percentages of Lin-CD122+ cells than PBMC. CD3-CD14-CD19-CD56- cells expressing CD122+ (a subunit of the IL-2 receptor) preferentially respond to HFWT feeder cells and are novel precursors of CD3-CD56+ NK cells in human PBMC and CBMC.


Non-coordinate regulation of RNA synthesis in Escherichia coli exposed to 0 degrees C.
A non-coordinate mode of regulation of RNA synthesis is observed in Escherichia coli cells during exposure to 0 degrees C. The stable RNA synthesis is preferentially inhibited with simultaneous accumulation of messenger RNA. The species of RNA synthesized at 0 degrees C was determined by several criteria such as sedimentation value in sucrose gradients, DNA-RNA hybridization, half life measurements, protein synthesizing capacity and its functional rate of decay. The mode of regulation of RNA synthesis at 0 degrees C is unique and is distinct from the non-coordinate regulation observed during amino acid starvation under stringent control.


The Defense of Involuntary Intoxication by Prescribed Medications: An Appellate Case Review.
The defense of involuntary intoxication has long been an exception to the general notion that intoxication is not a defense to criminal liability. The consumption of medications prescribed by a physician can form the basis of an involuntary-intoxication defense. In this article, I review cases where defendants relied on the use of prescribed medications for an involuntary-intoxication defense. The medications most frequently implicated by defendants are listed by name and by class. From the case law, I provide a summary of the defense and a review of the pitfalls of the defense to serve as practice pointers for forensic evaluators.


Machine learning approach for automatic quality criteria detection of health web pages.
The number of medical websites is constantly growing [1]. Owing to the open nature of the Web, the reliability of information available on the Web is uneven. Internet users are overwhelmed by the quantity of information available on the Web. The situation is even more critical in the medical area, as the content proposed by health websites can have a direct impact on the users' well being. One way to control the reliability of health websites is to assess their quality and to make this assessment available to users. The HON Foundation has defined a set of eight ethical principles. HON's experts are working in order to manually define whether a given website complies with s the required principles. As the number of medical websites is constantly growing, manual expertise becomes insufficient and automatic systems should be used in order to help medical experts. In this paper we present the design and the evaluation of an automatic system conceived for the categorisation of medical and health documents according to he HONcode ethical principles. A first evaluation shows promising results. Currently the system shows 0.78 micro precision and 0.73 F-measure, with 0.06 errors.


Nonlinear gain models in a quantum cascade laser.
Density matrix analysis of a three-state model of quantum cascade laser (QCL) reveals that in this device, the optical gain is composed of the linear part (proportional to population inversion Δn) and the remaining nonlinear part. The nonlinear component non-negligibly contributes even to the small-signal response of the medium. In many attempts to modeling QCLs, the common practice to account for nonlinear gain components is to complement the equation for the gain, g = gcΔn, gc is the gain cross-section, by a compression factor f. In this paper, improved (but still simple) models of the optical gain in QCL are proposed, which preserve the two-component gain structure. With these models, there is no need to solve the Hamiltonian with time-dependent potentials, so that extraordinary numerical loads can be avoided, but simultaneously the essential physics of the phenomena is kept. The improved gain models defined by Eqs. (12), (15) and (16) enable accounting for its nonlinear components while preserving the load-saving, scattering-like approach to light-matter interaction. It is also shown that as long as the populations and dc coherences are determined such that they account for the interaction with the optical field, the small-signal formulation of the gain gives its realistic estimate also for a large optical signal. This conjecture validates the use of non-equilibrium Green's function-based approaches, in which the interaction with the optical field is included through electron-photon selfenergies. The small-signal formulation of the gain can be used in this approach to monitor the saturation process, estimate the clamping flux and the light-current characteristic.


Dorsal midline cutaneous stigmata associated with occult spinal dysraphism in pediatric patients.
To investigate the prevalence of occult spinal dysraphism (OSD) and subsequent neurosurgery in pediatric patients with isolated or combined dorsal midline cutaneous stigmata with or without other congenital malformations. We carried out a retrospective review of patients who underwent sonography or magnetic resonance imaging (MRI) for OSD because of suspicion of dorsal midline cutaneous stigmata (presumed to be a marker for OSD) between January 2012 and June 2017. Information about patient characteristics, physical examination findings, spinal ultrasound and MRI results, neurosurgical notes, and accompanying congenital anomalies was collected. Totally 250 patients (249 ultrasound and one MRI screening) were enrolled for analysis. Eleven patients underwent secondary MRI examinations. The prevalence of OSD confirmed by an MRI was 2.4% (6 patients including one MRI screening). Five patients (2%) had tethered cord and underwent prophylactic neurosurgery, 3 of whom had a sacrococcygeal dimple and a fibrofatty mass. Prevalence of tethered cord increased as markers associated with a sacrococcygeal dimple increased (0.5% of the isolated marker group, 8.1% of the 2-marker group, and 50% of the 3-marker group). Incidence of OSD with surgical detethering in 17 other congenital anomaly patients was 11.8%, which was higher than the 1.3% in 233 patients without other congenital anomalies. Our results suggest that the presence of dorsal midline cutaneous stigmata, particularly fibrofatty masses, along with a sacrococcygeal dimple is associated with OSD or cord tethering requiring surgery. OSD should be suspected in patients with concurrent occurrence of other congenital anomalies.


Persistent Median Artery, Bifid Median Nerve, and Reversed Palmaris Longus Encountered During Cadaveric Dissection: The First Reported Case.
The median artery is a transient embryological structure that normally disappears with the development of the radial and ulnar arteries. In rare instances, though, it persists as the persistent median artery (PMA). The superficial and deep palmar arches are formed through the anastomoses of the radial and ulnar arteries, giving hand and digits their main blood supply. This complex network of vessels and their anastomoses are prone to anatomical variations based on how the anastomosis occurs and which arteries contribute to this anastomosis. While it normally forms through the anastomosis of the radial and ulnar arteries, the superficial palmar arch (SPA) may also form differently, as in our case here, where the median artery persisted and branched off the radial artery, anastomosing with the ulnar artery to give rise to the SPA. This may also interfere with the normal compartmental architecture within the hand, possibly contributing to various clinical pathologies like carpal tunnel syndrome (CTS). Notably, in addition to the persistent median artery, our findings revealed a reversed palmaris longus and a bifid median nerve. These two additional variations can potentially exacerbate the risk of CTS. Alone, the coexistence of the PMA and the reversed palmaris longus is deemed a rare anomaly, only reported once in the literature. The addition of a third variation to the existing ones, like the bifid median nerve, is first reported by us and calls for more investigation for a possible genetic mutation. In this case, we report a persistent median artery, reversed palmaris longus muscle, and bifid median nerve in the forearm of a male cadaver found during a routine anatomy teaching session.


The immune response to Plasmodium chabaudi malaria in interleukin-4-deficient mice.
Interleukin(IL)-4 promotes the development of T helper (TH)2 cells, induces immunoglobulin class switching to IgG1 and is thought to be essential for switching to IgE. During a primary infection with the erythrocytic stages of Plasmodium chabaudi chabaudi, TH1 and TH2 cells specific for the parasite appear sequentially as infection progresses. To dissect the possible role of TH2 responses at the later stages of infection, mice with a targetted disruption of the IL-4 gene were infected with P. chabaudi. IL-4-deficient mice were able to control and clear a primary infection, although recrudescent parasitemias were significantly higher in these mice compared with wild-type littermates; demonstrating that IL-4 per se is not required for parasite elimination. To evaluate the actual impairment of TH2 functions in the absence of IL-4 in vivo during an infection with P. chabaudi; the cellular and humoral responses to the parasite generated in vitro and in vivo were compared in the two types of mice. Our data indicate that in vitro TH1 responses and ex vivo IL-12 mRNA levels were sustained in the IL-4-deficient mice compared with wild-type littermates. Correspondingly, TH2-associated cytokine mRNA such as IL-5 and IL-6, but not IL-10, were reduced early in infection in the deficient animals. However, these cytokines were expressed at comparable levels at the later stages of infection in both types of mice. Reflecting these differences in TH function, IgG1 responses were decreased in vitro and delayed in vivo, whereas IgG2a and IgG2b responses appeared earlier in vivo in the deficient mice. Strikingly, IgE secretion was not blocked in vivo in the deficient mice; the onset of the synthesis of IgE mRNA was delayed during infection and the amount of circulating IgE was five times lower than in the wild-type littermates after 5 weeks of infection. All these impairments of TH2-related activities were insufficient to affect parasite clearance in the deficient mice, probably due to the fact that such activities were only delayed and could take place normally at the later stages of infection.


Synthesis of [5,6]-Bicyclic Heterocycles with a Ring-Junction Nitrogen Atom: Rhodium(III)-Catalyzed C-H Functionalization of Alkenyl Azoles.
The first syntheses of privileged [5,6]-bicyclic heterocycles, with ring-junction nitrogen atoms, by transition metal catalyzed C-H functionalization of C-alkenyl azoles is disclosed. Several reactions are applied to alkenyl imidazoles, pyrazoles, and triazoles to provide products with nitrogen incorporated at different sites. Alkyne and diazoketone coupling partners give azolopyridines with various substitution patterns. In addition, 1,4,2-dioxazolone coupling partners yield azolopyrimidines. Furthermore, the mechanisms for the reactions are discussed and the utility of the developed approach is demonstrated by iterative application of C-H functionalization for the rapid synthesis of a patented drug candidate.