A novel Lab-on-Fiber Radiation Dosimeter for Ultra-high Dose Monitoring.
In this work, we report on the first demonstration of Lab on Fiber (LOF) dosimeter for ionizing radiation monitoring at ultra-high doses. The new dosimeter consists in a metallo-dielectric resonator at sub-wavelength scale supporting localized surface plasmon resonances realized on the optical fiber (OF) tip. The resonating structure involves two gold gratings separated by a templated dielectric layer of poly(methyl methacrylate) (PMMA). Two LOF prototypes have been manufactured and exposed at the IRRAD Proton Facility at CERN in Geneva to 23 GeV protons for a total fluence of 0.67 × 1016 protons/cm2, corresponding to an absorbed dose of 1.8 MGy. Experimental data demonstrated the "radiation resistance" feature of the LOF devices and a clear dependence of the reflected spectrum versus the total dose, expressed by a cumulative blue-shift of ~1.4 nm of the resonance combined with a slight increase of 0.16 dBm in the reflected spectrum. The numerical analysis carried out to correlate the experimental results with the dimensional and physical properties of the resonator, expected to be tightly connected to the absorbed dose, suggests that the main phenomenon induced by exposure to proton beam and able to explain the measured spectral behavior is the reduction of the PMMA thickness, which is also consistent with past literature in the field. Preliminary results demonstrated the potentiality of the proposed platform as dosimeter at MGy dose levels for high energy physics experiments.


Very late thrombosis of a drug-eluting stent after discontinuation of dual antiplatelet therapy in a patient treated with both drug-eluting and bare-metal stents.
Drug-eluting stents (DESs) are the treatment of choice for obstructive coronary artery disease when percutaneous intervention is feasible. However, late stent thrombosis seems to occur more frequently with DESs and is closely associated with the discontinuation of dual antiplatelet therapy. We report a case of very late stent thrombosis after discontinuation of dual antiplatelet therapy. The patient suffered from acute myocardial infarction (MI) and underwent bare metal stent (BMS) implantation in the left anterior descending artery (LAD) five years prior to presentation. Three years after BMS implantation, he presented again with acute MI and had a DES implanted in the right coronary artery (RCA). He ran out of his medication, but failed to refill his prescription. Sixteen days after discontinuing medication, he experienced an episode of chest pain and was taken to the cardiac catheterization laboratory, where he was found to have thrombosis in the DES, but no thrombosis in the BMS. It is possible that DESs are more vulnerable to late thrombosis than are BMSs, supporting the use of prolonged dual antiplatelet therapy in patients treated with DESs. The patient was successfully treated with balloon angioplasty and thrombus aspiration without complications.


Comparison of long-term prognostic evaluation between pre-intervention thrombolysis and primary coronary intervention: a prospective randomized trial: five-year results of the IMPORTANT study.
Acute efficacy and long-term prognostic differences between ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (primary PCI) and those treated with pre-intervention thrombolysis combined with back-up of facilitated PCI has not been evaluated in Japanese patients. The purpose of the present study was therefore to evaluate the differences between treatment with primary PCI (primary-PCI group) and pre-treatment with tissue-type plasminogen activator (t-PA) combined with back-up of facilitated PCI (prior-t-PA group). One hundred and one patients with STEMI were randomly assigned to 2 groups. Patients in the prior-t-PA group were then divided into 2 further groups, the facilitated-PCI and prior-t-PA alone groups. The patency rate at initial angiography, left ventricular ejection fraction (LVEF) at 6 months, and the major adverse cardiac event (MACE)-free rate at 5 years were then compared between the groups. The patency rate and LVEF in the prior-t-PA group was significantly higher than in the primary-PCI group (69% vs 17% respectively, P<0.001; 61.6+/-9.5% vs 55.0+/-11.6%, respectively; P=0.01). The MACE-free rate in the prior-t-PA group, however, was lower than in the primary-PCI group (58.7% vs 80.9%; P=0.03). The MACE-free rate in the facilitated-PCI group was equal to that in the primary-PCI group (73.7% vs 80.9%; P=0.39), whereas the MACE-free rate in the prior-t-PA-alone group was significantly lower than in the primary-PCI group (48.1% vs 80.9%; P=0.01). Primary PCI is superior to pre-intervention thrombolysis for long-term prognosis. Moreover, facilitated PCI may be as effective as primary PCI in patients with STEMI.


Development of a serologic assay to detect Taenia solium taeniasis.
We developed a serologic assay to identify adult Taenia solium tapeworm carriers using excretory/secretory (TSES) antigens collected from in vitro cultured T. solium tapeworms. To identify taeniasis-specific antigens we used an immunoblot assay with serum samples from T. solium tapeworm carriers and cysticercosis patients. Antigens were identified that reacted with antibodies present in serum samples from taeniasis cases and not with those from cysticercosis patients. Using serum samples collected from persons with confirmed T. solium tapeworm infections, the test was determined to be 95% (69 of 73) sensitive. Serum samples (n = 193) from persons with other parasitic infections, including T. saginata tapeworm infections, do not contain cross-reacting antibodies to TSES, indicating that the assay is 100% specific. These data suggest that the immunoblot assay using TSES antigens can be used to identify persons with current or recent T. solium tapeworm infections and provides a new, important tool for epidemiologic purposes, including control and prevention strategies.


Interaction of mouse TTC30/DYF-1 with multiple intraflagellar transport complex B proteins and KIF17.
Intraflagellar transport (IFT) is a microtubule based system that supports the assembly and maintenance of cilia. Genetic and biochemical studies have identified two distinct complexes containing multiple proteins that are part of the IFT machinery. In this study we prepared mouse pituitary cells that expressed an epitope-tagged IFT protein and immuno-purified the IFT B complex from these cells. Mass spectrometry analysis of the isolated complex led to identification of a number of well known components of the IFT B complex. In addition, peptides corresponding to mouse tetratricopeptide repeat proteins, TTC30A1, TTC30A2 and TTC30B were identified. The mouse Ttc30A1, Ttc30A2, Ttc30B genes are orthologs of Caenorhabditis elegans dyf-1, which is required for assembly of the distal segment of the cilia. We used co-immunoprecipitation studies to provide evidence that, TTC30A1, TTC30A2 or TTC30B can be incorporated into a complex with a known IFT B protein, IFT52. We also found that TTC30B can interact with mouse KIF17, a kinesin which participates in IFT. In vitro expression in a cell-free system followed by co-immunoprecipitation also provided evidence that TTC30B can directly interact with several different IFT B complex proteins. The findings support the view that mouse TTC30A1, TTC30A2 and TTC30B can contribute to the IFT B complex, likely through interactions with multiple IFT proteins and also suggest a possible link to the molecular motor, KIF17 to support transport of cargo during IFT.


Invasion suppressor cystatin E/M (CST6): high-level cell type-specific expression in normal brain and epigenetic silencing in gliomas.
DNA hypermethylation-mediated gene silencing is a frequent and early contributor to aberrant cell growth and invasion in cancer. Malignant gliomas are the most common primary brain tumors in adults and the second most common tumor in children. Morbidity and mortality are high in glioma patients because tumors are resistant to treatment and are highly invasive into surrounding brain tissue rendering complete surgical resection impossible. Invasiveness is regulated by the interplay between secreted proteases (eg, cathepsins) and their endogenous inhibitors (cystatins). In our previous studies we identified cystatin E/M (CST6) as a frequent target of epigenetic silencing in glioma. Cystatin E/M is a potent inhibitor of cathepsin B, which is frequently overexpressed in glioma. Here, we study the expression of cystatin E/M in normal brain and show that it is highly and moderately expressed in oligodendrocytes and astrocytes, respectively, but not in neurons. Consistent with this, the CST6 promoter is hypomethylated in all normal samples using methylation-specific PCR, bisulfite genomic sequencing, and pyrosequencing. In contrast, 78% of 28 primary brain tumors demonstrated reduced/absent cystatin E/M expression using a tissue microarray and this reduced expression correlated with CST6 promoter hypermethylation. Interestingly, CST6 was expressed in neural stem cells (NSC) and markedly induced upon differentiation, whereas a glioma tumor initiating cell (TIC) line was completely blocked for CST6 expression by promoter methylation. Analysis of primary pediatric brain tumor-derived lines also showed CST6 downregulation and methylation in nearly 100% of 12 cases. Finally, ectopic expression of cystatin E/M in glioma lines reduced cell motility and invasion. These results demonstrate that epigenetic silencing of CST6 is frequent in adult and pediatric brain tumors and occurs in TICs, which are thought to give rise to the tumor. CST6 methylation may therefore represent a novel prognostic marker and therapeutic target specifically altered in TICs.


Multiplexed Strain Phenotyping Defines Consequences of Genetic Diversity in Mycobacterium tuberculosis for Infection and Vaccination Outcomes.
There is growing evidence that genetic diversity in Mycobacterium tuberculosis, the causative agent of tuberculosis, contributes to the outcomes of infection and public health interventions, such as vaccination. Epidemiological studies suggest that among the phylogeographic lineages of M. tuberculosis, strains belonging to a sublineage of Lineage 2 (mL2) are associated with concerning clinical features, including hypervirulence, treatment failure, and vaccine escape. The global expansion and increasing prevalence of this sublineage has been attributed to the selective advantage conferred by these characteristics, yet confounding host and environmental factors make it difficult to identify the bacterial determinants driving these associations in human studies. Here, we developed a molecular barcoding strategy to facilitate high-throughput, experimental phenotyping of M. tuberculosis clinical isolates. This approach allowed us to characterize growth dynamics for a panel of genetically diverse M. tuberculosis strains during infection and after vaccination in the mouse model. We found that mL2 strains exhibit distinct growth dynamics in vivo and are resistant to the immune protection conferred by Bacillus Calmette-Guerin (BCG) vaccination. The latter finding corroborates epidemiological observations and demonstrates that mycobacterial features contribute to vaccine efficacy. To investigate the genetic and biological basis of mL2 strains' distinctive phenotypes, we performed variant analysis, transcriptional studies, and genome-wide transposon sequencing. We identified functional genetic changes across multiple stress and host response pathways in a representative mL2 strain that are associated with variants in regulatory genes. These adaptive changes may underlie the distinct clinical characteristics and epidemiological success of this lineage. IMPORTANCE Tuberculosis, caused by the bacterium Mycobacterium tuberculosis, is a remarkably heterogeneous disease, a feature that complicates clinical care and public health interventions. The contributions of pathogen genetic diversity to this heterogeneity are uncertain, in part due to the challenges of experimentally manipulating M. tuberculosis, a slow-growing, biosafety level 3 organism. To overcome these challenges, we applied a molecular barcoding strategy to a panel of M. tuberculosis clinical isolates. This novel application of barcoding permitted the high-throughput characterization of M. tuberculosis strain growth dynamics and vaccine resistance in the mouse model of infection. Integrating these results with genomic analyses, we uncover bacterial pathways that contribute to infection outcomes, suggesting targets for improved therapeutics and vaccines.


IFN-γ-dependent activation of the brain's choroid plexus for CNS immune surveillance and repair.
Infiltrating T cells and monocyte-derived macrophages support central nervous system repair. Although infiltration of leucocytes to the injured central nervous system has recently been shown to be orchestrated by the brain's choroid plexus, the immunological mechanism that maintains this barrier and regulates its activity as a selective gate is poorly understood. Here, we hypothesized that CD4(+) effector memory T cells, recently shown to reside at the choroid plexus stroma, regulate leucocyte trafficking through this portal through their interactions with the choroid plexus epithelium. We found that the naïve choroid plexus is populated by T helper 1, T helper 2 and regulatory T cells, but not by encephalitogenic T cells. In vitro findings revealed that the expression of immune cell trafficking determinants by the choroid plexus epithelium is specifically induced by interferon-γ. Tumour necrosis factor-α and interferon-γ reciprocally controlled the expression of their receptors by the choroid plexus epithelium, and had a synergistic effect in inducing the epithelial expression of trafficking molecules. In vivo, interferon-γ-dependent signalling controlled trafficking through the choroid plexus; interferon-γ receptor knockout mice exhibited reduced levels of T cells and monocyte entry to the cerebrospinal fluid and impaired recovery following spinal cord injury. Moreover, reduced expression of trafficking molecules by the choroid plexus was correlated with reduced CD4(+) T cells in the choroid plexus and cerebrospinal fluid of interferon-γ receptor knockout mice. Similar effect on the expression of trafficking molecules by the choroid plexus was found in bone-marrow chimeric mice lacking interferon-γ receptor in the central nervous system, or reciprocally, lacking interferon-γ in the circulation. Collectively, our findings attribute a novel immunological plasticity to the choroid plexus epithelium, allowing it to serve, through interferon-γ signalling, as a tightly regulated entry gate into the central nervous system for circulating leucocytes immune surveillance under physiological conditions, and for repair following acute injury.


Recent advances in acute kidney injury epidemiology.
Expanding rates of acute kidney injury (AKI) coupled with increasing awareness of its short-term and long-term sequelae have focused efforts to identify patients at risk for this disease and its complications. This review details the recent attempts to identify novel risk factors for AKI, describes further refinements in the diagnostic and prognostic approach using biological markers of injury, and highlights the features of AKI that independently predict poor long-term outcomes. The presence of proteinuria predicts the development of AKI independently of estimated glomerular filtration rate. Initial results from a large prospective study of AKI biomarkers in cardiac surgery indicate lower agreement with serum creatinine as an AKI standard than observed in early studies. AKI severity and duration are important predictors of chronic kidney disease and long-term mortality. A minority of patients surviving AKI with decreased kidney function is seen by a nephrologist. Although the pathophysiologic link is unclear, proteinuria is an easily measurable risk factor for AKI worth considering before anticipated procedures or medication exposures carrying nephrologic risk. Investigation extending beyond agreement with serum creatinine is needed to fully understand the diagnostic and prognostic value of AKI biomarkers. Severity and duration are components of AKI that can help risk-stratify survivors in need of monitoring or nephrology referral.


Atg7 Overcomes Senescence and Promotes Growth of BrafV600E-Driven Melanoma.
Macroautophagy (autophagy hereafter) may promote survival and growth of spontaneous tumors, including melanoma. We utilized a genetically engineered mouse model of melanoma driven by oncogenic BrafV600E and deficiency in the Pten tumor suppressor gene in melanocytes to test the functional consequences of loss of the essential autophagy gene autophagy-related-7, Atg7. Atg7 deficiency prevented melanoma development by BrafV600E and allelic Pten loss, indicating that autophagy is essential for melanomagenesis. Moreover, BrafV600E-mutant, Pten-null, Atg7-deficient melanomas displayed accumulation of autophagy substrates and growth defects, which extended animal survival. Atg7-deleted tumors showed increased oxidative stress and senescence, a known barrier to melanomagenesis. Treatment with the BRAF inhibitor dabrafenib decreased tumor growth and induced senescence that was more pronounced in tumors with Atg7 deficiency. Thus, Atg7 promotes melanoma by limiting oxidative stress and overcoming senescence, and autophagy inhibition may be of therapeutic value by augmenting the antitumor activity of BRAF inhibitors. The essential autophagy gene Atg7 promotes development of BrafV600E-mutant, Pten-null melanomas by overcoming senescence, and deleting Atg7 facilitated senescence induction and antitumor activity of BRAF inhibition. This suggests that combinatorial BRAFV600E and autophagy inhibition may improve therapeutic outcomes in patients whose tumors have BRAFV600E/K mutations, an approach currently being explored in clinical trials.


Enhanced ultrasonography using a nano/microbubble contrast agent for islet transplantation.
Recent basic and clinical studies have assessed the use of highly sensitive imaging modalities for visualizing transplanted islets. We investigated the utility of enhanced ultrasonography, combined with fluorescent acoustic liposome nano/microbubbles (FALs), for evaluating angiogenesis and the endocrine function of transplanted islets. BALB/c mice were classified into three groups: Diabetic mice that underwent syngeneic islet transplantation into the subrenal capsule and achieved normoglycemia (Tx group); those that failed to achieve normoglycemia (Tx-DM group); and those not receiving any treatment (DM group). Mice were examined by FAL-enhanced high frequency ultrasonography. The echogenicity of the islets increased rapidly within the first minute after injection of FALs and remained at a higher level in the Tx group, while small increases were observed in the other two groups. In histological assessments, fluorescently stained erythrocytes could be seen in and around the transplanted islets, indicating that the transplanted islets were enhanced by infusion of FALs via vessel networks between the engrafted islets and tissue. Furthermore, the echogenicity correlated significantly with endocrine parameters, including blood glucose (BG), serum insulin, and the BG change in the glucose tolerance test. In conclusion, the echogenicity of the islets under FAS-enhanced ultrasonosonography correlated with the endocrine status of transplanted islets.


Recent advances in the prevention and treatment of congenital cytomegalovirus infections.
Continued but slow progress has led to recent advances in our understanding that congenital cytomegalovirus (CMV) infection has occurred. We understand that the most severe congenital disease occurs following a primary maternal infection during pregnancy. We now have the ability to accurately diagnosis a primary maternal infection using serologic studies of single serum sample. For pregnant women with young children, we know that child-to-mother CMV transmission can probably be prevented by hygienic intervention, and that for pregnant women who have acquired a primary CMV infection, mother-to-fetal transmission is probably preventable using CMV hyperimmune globulin. Although additional studies are needed, treatment of congenitally infected fetuses or newborns should be possible using either CMV hyperimmune globulin or antiviral agents such as ganciclovir or its derivates. Finally, recent evidence indicates that CMV replicates in the placenta, impairs development, and causes inflammation and dysfunction. This plus the reversibility of many manifestations of congenital infection in the fetus and newborn indicate that congenital CMV disease is in part a syndrome of placental insufficiency.


Epiphyte size and taxonomy as biological indicators of ecological and toxicological factors in Lake Saint-François (Québec).
To assess the potential of the epiphyton community for monitoring spatial and temporal variations in the environmental quality of freshwater ecosystems, this paper describes the response of epiphytons to ecological and toxicological factors in Lake Saint-François, a fluvial lake of the St. Lawrence River (Québec). First, community descriptions and biotic indices based on size structure and on taxonomic composition were compared to test if size could usefully describe epiphyton response to environmental factors. Secondly, the relative contribution of ecological and toxicological variables in explaining the variation observed in epiphyton was quantified. A size-based approach classified the sites similarly to taxonomic analysis, but a larger portion of variance in size could be explained indicating a stronger relationship with environmental factors. Among both taxonomy and size-based biotic indices, the slope of the normalized size spectra performed best in terms of total explained variance. There were strong interactions between toxicological and ecological variables. These interactions should be considered in the planning and interpretation of biomonitoring studies. In such surveys, samples should be collected at sites with similar ecological characteristics: for example, the same macrophyte type and sediment texture. Interpretation of the data should consider the possible covariance of toxicological and ecological variables.


Three-dimensional double helical DNA structure directly revealed from its X-ray fiber diffraction pattern by iterative phase retrieval.
Coherent diffraction imaging (CDI) allows the retrieval of an isolated object's structure, such as a macromolecule, from its diffraction pattern. CDI requires the fulfillment of two conditions: the imaging radiation must be coherent and the object must be isolated. We discuss that it is possible to directly retrieve the molecular structure from its diffraction pattern, which was acquired neither with coherent radiation nor from an individual molecule. This is provided that the molecule exhibits periodicity in one direction, as in the case of fiber diffraction. We demonstrate that, when we apply iterative phase retrieval methods to a fiber diffraction pattern, the repeating unit; that is, the molecule structure, can directly be reconstructed without any prior modeling. For example, we recover the the DNA double helix's structure in three-dimensions from its two-dimensional X-ray fiber diffraction pattern, Photograph (Photo) 51, which was acquired in Raymond Gosling and Rosalind Franklin's famous experiment at a resolution of 3.4 Å.


[Comparative study of antigens specific for hepatitis B in transfected cell cultures].
A comparative study of antigens detected in the livers of patients with hepatitis B. in the mesonephros of the human tissue--chick embryo system infected with the agents isolated from the blood of hepatitis patients, as well as antigens detectable in cell cultures transfected by the DNA isolated from these tissues was carried out. The results are in favour of the hypothesis on the integrational nature of serum hepatitis.


Audit and feedback of therapist-assisted internet-delivered cognitive behaviour therapy within routine care: A quality improvement case study.
With the growing use of ICBT in routine care clinics there is a need for literature on how to monitor and improve the quality of therapist behaviours in clinical practice. In this paper, we first provide background literature on Audit and Feedback (A&F), a common quality improvement technique, and then present a case study regarding the use of A&F to improve quality of therapist behaviours in emails sent to patients provided with ICBT in routine care. The A&F measure used was derived from previous research on therapist's email behaviours in ICBT. Fifteen undesirable therapist behaviours (e.g., Did Not Message, Unresponsive to Symptom Increase, Does Not Address Patient Concern) were audited in 1840 emails sent from eight therapists to 198 randomly selected patients, representing 18% of 1114 patients who started between one and five lessons of ICBT in the previous year and did not formally withdraw from treatment (n = 31 patients). The therapists who were audited were provided feedback four times over a one-year period from October 2018 to September 2019. Overall, in all audit periods, we found a low percentage of undesirable therapist behaviours (i.e., therapists displayed the behaviour in 12% or less of the total emails sent). For most therapist behaviours, we saw a trend towards improvement across the four audit cycles. Three therapist behaviours (i.e., Failure to Ask One Question to the Patient, Poor Instructions, Not Linking Email to Course Content) did not follow this pattern and were flagged for clinical discussion to determine why behaviours were elevated and whether these behaviours represented unrealistic expectations. The process was valuable for monitoring and improving therapist behaviours and highlights the need for future research on standards for therapist behaviours (e.g., which behaviours to focus on, setting acceptable levels of undesirable behaviour).


Radical retropubic prostatectomy in immunosuppressed transplant recipients.
Surgical treatment of transplant recipients in whom prostate cancer subsequently develops has been reported only sporadically in the literature. We reviewed our experience with radical retropubic prostatectomy in patients with solid organ transplants. Using our prostatectomy registry we identified 17 patients who underwent radical retropubic prostatectomy between 1988 and 2005 following organ transplantation. Clinicopathological features and outcome data were reviewed. Kidney, liver and heart transplants were performed before radical retropubic prostatectomy in 9, 7 and 3 patients, respectively. Median age at transplant and time of radical retropubic prostatectomy was 51 (range 37 to 65) and 59 years (range 45 to 70), respectively. Median prostate specific antigen was 5.8 (range 2.6 to 12.9) and all patients had clinically localized disease. Ten patients had a pathological Gleason score of 6 while the remaining had Gleason scores 7 or greater. No patient had positive lymph nodes and only 2 patients had pT3a or greater disease. Early complications included wound infection in 2 (12%) patients along with hematoma and myocardial infarction in 1 (6%) patient each. Late complications included incontinence (1 or more pads per day) in 2 patients while no patient had a hernia, bladder neck contracture, venous thrombosis or lymphocele. With a median followup of 4.9 years, biochemical recurrence developed in 1 patient and no patient had systemic progression or death due to prostate cancer. To our knowledge we report the largest experience with radical retropubic prostatectomy in transplant recipients. Our results suggest that radical retropubic prostatectomy is feasible for immunosuppressed patients, yet concern for infection and wound healing remain important. Healthy transplant recipients with an increased prostate specific antigen should undergo a prostate biopsy.


Electrostatic properties of fiber cell membranes from the frog lens.
The electrostatic properties of lens fiber cell membranes have been investigated by recording the electrophoretic mobility of membrane vesicles formed from isolated fiber cells. The vesicles appear to be sealed and have external surfaces that are representative of the extracellular surface of fiber cells. The average mobility of a vesicle in normal Ringer's solution was 0.9 microns/s per v/cm, which gives a zeta potential of -9 mV, a value similar to that reported for other cells (McLaughlin, S. 1989. Annu. Rev. Biophys. Biophys. Chem. 18:113-136.). There was no significant difference in the mobility of vesicles formed from peripheral, middle cortical, or nuclear fiber cells. Vesicle surface changes were titrated using Ca and Mg and each had a pK of approximately 2, which is similar to that for the most common phospholipids. We also titrated these charges with varying pH and found the most significant changes in mobility at pH values between 5 and 6. The majority of lipids found in biological membranes are not titratable in this pH range, so the pH effect is probably through a membrane protein charged group. These experimental data in conjunction with the previously measured extracellular voltage gradient (Mathias, R. T., and J. L. Rae. 1985. Am. J. Physiol. 249:C181-C190) imply that electroosmosis can generate a fluid velocity of approximately 0.6 mm/h, directed from the aqueous or vitreous toward the center of the lens, along intercellular clefts.


Neuroscience. Regional differences in cortical organization.
Although there are elegants maps of the human brain that reveal differences in cellular architecture between different cortical regions, there is not much information about how corresponding cortical regions differ between the left and right hemispheres. As Gazzaniga explains in his Perspective, new results reveal the surprising finding of asymmetry in area 22 (which is important for language processing) of the left and right hemisphere (Galuske et al.). Clusters of neurons in area 22 of the left hemisphere are spaced farther apart and have longer axons cabling them together than neuronal clusters in area 22 of the right hemisphere.


Long live lamins.
Mutations in genes encoding nuclear lamins cause diseases called laminopathies. In this issue, Hasper et al. (https://doi.org/10.1083/jcb.202307049) show that lamin A/C and the prelamin A variant in Hutchinson-Gilford progeria syndrome have relatively long lifetimes in affected tissues.


National Patterns and Outcomes of Neurologist Care in Acute Ischemic Stroke.
Specialist care of acute ischemic stroke patients has been associated with improved outcomes but is not well-characterized. We sought to elucidate the involvement and influence of neurologists on acute ischemic stroke care. Using 100% Medicare datasets, index acute ischemic stroke admissions from 2016-2018 were identified with International Classification of Diseases, 10th Revision codes. Neurologists were identified by NPI code. Neurologist involvement in care was defined as: "neurologist involved in care"; "hospital with a neurologist"; and "percent of acute ischemic stroke treated by neurologist." Adjusted logistic regression models summarized exposure to neurologists and their association with outcomes (inpatient mortality, good outcome, and 30-day readmission). Among 647838 index AIS admissions from 2016-2018, 15.6% included a neurologist involved in care, associated with receiving intravenous thrombolysis (19.1% vs 6.5%), endovascular thrombectomy (13.2% vs 1.4%), treatment at a teaching hospital (87.7% vs 55.5%), and treatment at a hospital in the highest volume quartile (95.3% vs 75.6%). Of 4797 hospitals, 36.1% had a neurologist, among which the mean percent of admissions treated by a neurologist was 14.7% (SD 24.4). Neurologist involvement was associated with increased inpatient mortality (OR 1.81; 95% CI 1.75-1.86), decreased odds of a good outcome (OR .92; 95% CI .90-.93), and increased 30-day readmission (OR 1.04; 95% C: 1.01-1.06). The minority of acute ischemic stroke admissions among the elderly in the US are treated by neurologists. Neurologist involvement in care is associated with worse outcomes, possibly from the allocation of severe cases to neurologists.


Effect of HMGcoA reductase inhibitors on stroke. A meta-analysis of randomized, controlled trials.
Stroke is a leading cause of death in the industrialized world, and hypercholesterolemia may be a risk factor for stroke. To determine whether reducing cholesterol levels with HMGcoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibitors or other antilipidemic interventions reduces risk for nonfatal and fatal stroke. A systematic search in the MEDLINE and EMBASE databases of the English-language and non-English-language literature published from 1966 through October 1996. All randomized, controlled trials of any cholesterol-lowering intervention that reported data on nonfatal and fatal strokes, on death from coronary heart disease, and on overall mortality were included. Whether treatment effects differed according to the type of cholesterol-lowering intervention used was investigated. Trials were reviewed for methods, inclusion and exclusion criteria, and outcomes. 28 trials (for a total of 49,477 study participants in the intervention group and 56,636 participants in the control group) were included. The risk ratio for nonfatal and fatal stroke with HMGcoA reductase inhibitors was 0.76 (95% CI, 0.62 to 0.92; test of heterogeneity, P > 0.2). The risk ratios for nonfatal and fatal stroke with fibrates, resins, and dietary interventions were all close to 1.0, and the difference between the HMGcoA reductase inhibitor effect and the pooled estimate for all other interventions would, under the null hypothesis, be unlikely to occur by chance (P = 0.01). Trials with HMGcoA reductase inhibitors also showed reductions in rates of death from coronary heart disease and overall mortality. This meta-analysis of randomized, controlled trials suggests that in hyperlipidemic patients who have not previously had stroke, HMGcoA reductase inhibitors reduce the incidence of stroke.


An Evaluation of the Pea Pod System for Assessing Body Composition of Moderately Premature Infants.
(1) BACKGROUND: Assessing the quality of growth in premature infants is important in order to be able to provide them with optimal nutrition. The Pea Pod device, based on air displacement plethysmography, is able to assess body composition of infants. However, this method has not been sufficiently evaluated in premature infants; (2) METHODS: In 14 infants in an age range of 3-7 days, born after 32-35 completed weeks of gestation, body weight, body volume, fat-free mass density (predicted by the Pea Pod software), and total body water (isotope dilution) were assessed. Reference estimates of fat-free mass density and body composition were obtained using a three-component model; (3) RESULTS: Fat-free mass density values, predicted using Pea Pod, were biased but not significantly (p > 0.05) different from reference estimates. Body fat (%), assessed using Pea Pod, was not significantly different from reference estimates. The biological variability of fat-free mass density was 0.55% of the average value (1.0627 g/mL); (4) CONCLUSION: The results indicate that the Pea Pod system is accurate for groups of newborn, moderately premature infants. However, more studies where this system is used for premature infants are needed, and we provide suggestions regarding how to develop this area.


Nurse staffing and patient mortality in intensive care units.
Research evidence suggests that nurse staffing influences patient outcomes. To examine the relationship between nurse staffing and patient mortality in Korean intensive care units (ICUs). Using survey and administrative databases, this study included 27,372 ICU patients discharged from 42 tertiary and 194 secondary hospitals. Ownership (public vs. private), location (metropolitan city vs. province), size, specialization of ICUs (specialized vs. mixed), physician staffing and nurse staffing, and years of nurse experience were included as hospital and ICU characteristics. Nurse staffing was measured as the ratio of average daily census to the total number of full-time equivalent registered nurses in ICUs. Age, gender, 26 categories of primary diagnoses, 16 groups of comorbid conditions, and source of payment were used for risk adjustment. Mortality was defined as deaths that occurred in the hospital or on the date of hospital discharge. Using SAS GLIMMIX procedures, multivariate logistic regression analysis was employed separately for tertiary and secondary hospitals. In tertiary hospitals, a greater likelihood of dying was found among patients who were admitted to a mixed ICU (odds ratio [OR] = 1.61, 95% confidence interval [CI] = 1.14-2.26) and where there was no board-certified physician present for 4 or more hours per day (OR = 1.56, 95% CI = 1.20-2.01). In secondary hospitals, every additional patient per RN was associated with a 9% increase in the odds of dying (OR = 1.09, 95% CI = 1.04-1.14). Nurse experience had no significant relationship with mortality. Nurse and physician staffing and specialization of ICUs impacted patient mortality. Associations differed in tertiary and secondary hospitals. Further investigation of the impact of organizational environments in ICUs is needed.


Identification of seven new alpha2,3-sialyltransferase III, ST3Gal III, transcripts from human foetal brain.
We have recently cloned and sequenced 19 human ST3Gal III gene isotranscripts from peripheral blood leukocytes and identified very complex patterns of isotranscripts of this gene in neuronal tissues. We have now cloned and sequenced additionally seven new isotranscripts from foetal brain. These novel isotranscripts showed losses of complete exons along the whole length of the coding sequence. None of the new isotranscripts coded for proteins with the two (L- and S-) sialylmotifs intact. One of the isotranscripts belonged to the isoform ST3Gal III -B, five to the ST3Gal III -C isoform and one to ST3Gal III -D isoform of isotranscripts, which lacks exon 3, exons 3 and 4 and exon 4 respectively. Two of the C series isotranscripts, ST3Gal III C4 and C11 had both lost exons 12 and 13 containing the S-motif but had otherwise the L- and the VS-motifs intact. Three isotranscripts, ST3Gal III C5, C12 and D5, were similar in the 3'-end coding for an identical amino acid sequence unrelated to the original enzyme. Isotranscripts ST3Gal III C9 and B10 were distinctly different from all other forms identified so far. The splice variants reported here are unlikely to express enzymatic activities but may other biological functions.


Fuel poverty in Scotland: refining spatial resolution in the Scottish Fuel Poverty Indicator using a GIS-based multiple risk index.
Fuel poverty describes a complex interaction between households with low income and energy inefficiency. The Scottish Executive has charged local Scottish authorities with the task of eradicating fuel poverty by 2016. In order to direct investment and tackle fuel poverty, a local authority must know which areas are more likely to contain fuel poor households. Currently, local area fuel poverty indicators, based on small area statistics, are used to identify target areas. This paper proposes an innovative methodology for refinement of the Scottish Fuel Poverty Indicator using GIS as a framework for integrating census data with georeferenced energy efficiency data on local housing stock. This allows a multi-scale mapping of fuel poverty risk at both a census output area level and an individual dwelling level. The proposed methodology highlights small areas, and households, possibly susceptible to fuel poverty previously masked by the aggregation of statistics to large geographic units.


Sex and hormonal cycle differences in rat brain levels of pain-related cannabimimetic lipid mediators.
One important function of endocannabinoids and related lipid mediators in mammalian central nervous system is modulation of pain. Evidence obtained during the last decade shows that altered levels of these compounds in the brain accompany decreases in pain sensitivity. Such changes, if sexually dimorphic, could account for sex differences in pain and differences that occur during different phases of the hormonal cycle in females. To examine this possibility, we measured the levels of the pain-modulatory lipids anandamide, 2-arachidonoyl glycerol, N-arachidonoyl glycine, N-arachidonoyl gamma amino butyric acid, and N-arachidonoyl dopamine in seven different brain areas (pituitary, hypothalamus, thalamus, striatum, midbrain, hippocampus, and cerebellum) in male rats, and in female rats at five different points in the estrous cycle. The cerebellum did not demonstrate a change in endocannabinoid production across the estrous cycle, whereas all other areas tested showed significant differences in at least one of the compounds measured. These changes in levels occurred predominantly within the 36-h time period surrounding ovulation and behavioral estrus. Differences between males and females were measured as either estrous cycle-independent (all estrous cycles combined) or cycle-dependent (comparisons of males to each estrous cycle). In cycle-independent analyses, small sex differences were observed in the pituitary, hypothalamus, cerebellum, and striatum, whereas no differences were observed in the thalamus, midbrain, and hippocampus. In cycle-dependent analyses, the hypothalamus and pituitary showed largest sex differences followed by the striatum, midbrain, and hippocampus, whereas no sex differences were measured in thalamus and cerebellum. These data provide a basis for investigations into how differences in sex and hormonal status play a role in mechanisms regulating endocannabinoid production and pain.


The addition of strength training to aerobic interval training: effects on muscle strength and body composition in CHF patients.
The loss of lean muscle mass and muscle strength is a common problem in chronic heart failure (CHF) patients. Endurance training is efficient in improving patient exercise capacity. This study sought to evaluate the additional effects of strength training on muscle strength and body composition in chf patients participating in an interval training program. Twenty consecutive, stable CHF patients participated in a rehabilitation program. Subjects were randomly assigned to aerobic (n = 10) or combined aerobic plus strength training group (n = 10). Aerobic group performed interval training on cycle ergometers. Strength training incorporated exercises for various muscle groups, including quadriceps, hamstrings, biceps brachii, and the deltoids. Both regimes were of the same duration. Body composition was evaluated by whole-body dual energy x-ray absorptiometry and quadriceps strength by the sum of the 2-repetition maximum (2-RM) test for each leg. Peak oxygen uptake (.VO(2peak)) and peak work load (W(peak)) as well as oxygen uptake (.VO(2AT)) and workload at anaerobic threshold (W(AT)) were evaluated by a symptom limited cardiopulmonary exercise testing. Concerning leg lean mass, no significant within-subjects or between-groups changes were observed (P > .05). Both groups improved in 2-RM test (P < .05), while a significant difference was observed between groups (P < .05). .VO(2peak) and .VO(2AT) and W(peak) and W(AT) were equally improved between training groups (P < .05). Combined aerobic interval and strength training induces a greater benefit than interval training alone on muscle strength in CHF patients. Adaptations other than hypertrophy, such as muscle fiber type alterations and/or neuromuscular adjustments, may account for these results.


The evolution of the system of radiological protection: the justification for new ICRP recommendations.
ICRP has been encouraging discussion during the past few years on the best way of expressing radiological protection philosophy in its next recommendations, which it plans to publish in 2005. The present recommendations were initiated by Publication 60 in 1990 and have been complemented by additional publications over the last 12 years. It is now clear that there is a need for the Commission to summarise the totality of the number of numerical values that it has recommended in some ten reports. This has been done in this paper, and from these a way forward is indicated to produce a simplified and more coherent statement of protection philosophy for the start of the 21st century. A radical revision is not envisaged, rather a coherent statement of current policy and a simplification in its application.


[Effect of coamide and folicobalamin on erythropoiesis during ordinary vital activities and in head-down tilt hypokinesia].
The study was performed on 41 healthy men, aged 19 to 40, who led a normal life or were exposed to short-term or long-term head-down tilts. The effectiveness of hemostimulants was determined with respect to hemoglobin, red blood cells or reticulocyte counts. Folicobalamine and coamide administration in therapeutic doses increased hemoglobin and reticulocyte blood levels in the ambulant subjects or those exposed to a 7-day head-down tilt. The effect was stable and persisted for 2-3 weeks after which the blood parameters returned to the pretest level. Folicobalamine administered at the final stage of 50-day head-down tilt facilitated partial recovery of hemoglobin during the study (which is very important) and rapid recovery after it. The objective and subjective tolerance of the drugs was good. It is therefore concluded that folicobalamine should be taken at the final stage of head-down tilt or space flight to alleviate readaptation to the normal environment.


[Artificial "membranous lung"].
The paper reviews and anlyses the most widespread up-to-date designs of membranous oxygenators. On an example of some types of membraneous oxygenators and their functional characteristics basic parameters for a comparative evaluation and choice of the "membranous lung" and its effective utilization have been deduced, viz. the circulation rate, the rate of the oxygen and carbon dioxide transport (per 1 m2 of the oxygenating surface), pressure differential, primarily filled up volume and oxygen consumption. The authors underline the need for determining the efficiency of the oxygenator with reference to O2 and CO2 and standard values of unsaturated blood indices. With due regard for promising trends in the future development of artificial "membranous lungs" features that may be of use in the classification of membraneous oxygenators have been systematized.


[A novel diagnostic measure of platelet-specific antibody in immune thrombocytopenia].
To detect the platelet glycoprotein-specific antibodies in serum of thrombocytopenia patients and evaluate its diagnostic value for immune thrombocytopenia. Anti-GPIIb/IIIa, GPIb/IX and GPIa/IIa antibodies were assayed by ELISA kit (PAKUTO) in patients with thrombocytopenia. The sensitivity and specificity of PAKAUTO in immune thrombocytopenia were 44.0% and 95.7%, respectively. The values of positive and negative predictions were 98.0% and 26.2%, respectively. Among those PAKAUTO positive patients, positive rates of GPIIb/IIIa, GPIa/IIa and GPIb/IX were 87%, 35% and 10%, respectively. The positive rate of patients not received immune suppressive agents (58.5%) was significantly higher than those received immune suppressive agents (26.9%) (P < 0.01). The positive rate of patients with platelet count ≤ 20 × 10(9)/L (51.6%) was significantly higher than those with platelet count > 20 × 10(9)/L (27.8%) (P < 0.01). The positive rate of patients with secondary immune thrombocytopenia (66.7%) was significantly higher than those with primary immune thrombocytopenia (41.7%) (P < 0.05). The highly specific method (PAKAUTO) could effectively differentiate immune or non-immune thrombocytopenia and be applied to diagnosis of immune thrombocytopenia.


The effect of sweeteners on acid production in plaque.
In studies of the pH response of dental plaque in situ to rinses with conventional sugars, glucose and maltose give similar falls in pH, and fructose only slightly smaller effects compared with sucrose. Lactose and galactose are less acidogenic, while the pH response to glucose syrups varies according to their composition. Of the sugar alcohols, sorbitol, mannitol, maltitol and lactitol are all slowly fermented to acid by oral bacterial, and xylitol is virtually non-fermentable. Acid formation in plaque by fermentable sugar alcohols can be too slow to overcome the buffering power of plaque and saliva and plaque pH can rise following exposure to these compounds. Lycasin, a synthetic sweetener containing sorbitol, maltitol and some higher sugar alcohols gives effects similar to its major constituents. Palatinit, L-sorbose and trichlorogalactosucrose are of low acidogenicity, but coupling sugar is more fermentable and can give rise to a substantial pH response, albeit less than sucrose. Non-nutritive intense sweeteners may affect plaque pH by their sialogogue effects.


Pharmacological characterization of Ca2+ entry channels in endothelin-1-induced contraction of rat aorta using LOE 908 and SK&F 96365.
We have recently shown that endothelin-1 (ET-1) activates two types of Ca2+-permeable nonselective cation channels (designated NSCC-1 and NSCC-2) and store-operated Ca2+ channel (SOCC). These channels can be pharmacologically discriminated using Ca2+ channel blockers such as SK&F 96365 and LOE 908. Here we characterized Ca2+ entry channels involved in ET-1-induced contractions of rat thoracic aortic rings and increases in the intracellular free Ca2+ concentration ([Ca2+]i) of single smooth muscle cells using these blockers. LOE 908 or a blocker of voltage-operated Ca2+ channel nifedipine had no effect on the contractions and increases in [Ca2+]i induced by thapsigargin or ionomycin, whereas SK&F 96365 abolished them. The contractions and increases in [Ca2+]i induced by ET-1 depended on extracellular Ca2+ but were resistant to nifedipine. The responses to lower concentrations (< or =0.1 nM) of ET-1 were abolished by either SK&F 96365 or LOE 908. The responses to higher concentrations (> or = 1 nM) were abolished by SK&F 96365, but were partially resistant to LOE 908. SK&F 96365 inhibited the LOE 908-resistant contractions induced by higher concentrations of ET-1 with IC50 values similar to those for contractions induced by thapsigargin or ionomycin. These results show that the contractions and increases in [Ca2+]i of rat aortic smooth muscles at lower concentrations of ET-1 involve only one Ca2+ entry channel which is sensitive to SK&F 96365 and LOE 908 (NSCC-2), whereas those at higher concentrations of ET-1 involve another Ca2+ entry channel which is sensitive to SK&F 96365 but resistant to LOE 908 (SOCC) in addition to the former channel.


Insertion torque versus mechanical resistance of mini-implants inserted in different cortical thickness.
This study aimed to measure insertion torque, tip mechanical resistance to fracture and transmucosal neck of mini-implants (MI) (Conexão Sistemas de PróteseT), as well as to analyze surface morphology. Mechanical tests were carried out to measure the insertion torque of MIs in different cortical thicknesses, and tip mechanical resistance to fracture as well as transmucosal neck of MIs. Surface morphology was assessed by scanning electron microscopy (SEM) before and after the mechanical tests. Values of mechanical resistance to fracture (22.14 N.cm and 54.95 N.cm) were higher and statistically different (P < 0.05) from values of insertion torque for 1-mm (7.60 N.cm) and 2-mm (13.27 N.cm) cortical thicknesses. Insertion torque was statistically similar (P > 0.05) to torsional fracture in the tip of MI (22.14 N.cm) when 3 mm cortical thickness (16.11 N.cm) and dense bone (23.95 N.cm) were used. Torsional fracture of the transmucosal neck (54.95 N.cm) was higher and statistically different (P < 0.05) from insertion torsional strength in all tested situations. SEM analysis showed that the MIs had the same smooth surface when received from the manufacturer and after the mechanical tests were performed. Additionally, no significant marks resulting from the manufacturing process were observed. All mini-implants tested presented adequate surface morphology. The resistance of mini-implants to fracture safely allows placement in 1 and 2-mm cortical thickness. However, in 3-mm cortical thickness and dense bones, pre-drilling with a bur is recommended before insertion.


Proteoglycans and their heterogeneous glycosaminoglycans at the atomic scale.
Proteoglycan spatiotemporal organization underpins extracellular matrix biology, but atomic scale glimpses of this microarchitecture are obscured by glycosaminoglycan size and complexity. To overcome this, multimicrosecond aqueous simulations of chondroitin and dermatan sulfates were abstracted into a prior coarse-grained model, which was extended to heterogeneous glycosaminoglycans and small leucine-rich proteoglycans. Exploration of relationships between sequence and shape led to hypotheses that proteoglycan size is dependent on glycosaminoglycan unit composition but independent of sequence permutation. Uronic acid conformational equilibria were modulated by adjacent hexosamine sulfonation and iduronic acid increased glycosaminoglycan chain volume and rigidity, while glucuronic acid imparted chain plasticity. Consequently, block copolymeric glycosaminoglycans contained microarchitectures capable of multivalent binding to growth factors and collagen, with potential for interactional synergy at greater chain number. The described atomic scale views of proteoglycans and heterogeneous glycosaminoglycans provide structural routes to understanding their fundamental signaling and mechanical biological roles and development of new biomaterials.


Zero-Field NMR J-Spectroscopy of Organophosphorus Compounds.
Organophosphorus compounds are a wide and diverse class of chemicals playing a crucial role in living organisms. This aspect has been often investigated using nuclear magnetic resonance (NMR), which provides information about molecular structure and function. In this paper, we report the results of theoretical and experimental studies on basic organophosphorus compounds using zero-field NMR, where spin dynamics are investigated in the absence of a magnetic field with the dominant heteronuclear J-coupling. We demonstrate that the zero-field NMR enables distinguishing the chemicals owing to their unique electronic environment even though their spin systems have the same alphabetic designation. Such information can be obtained just in a single measurement, while amplitudes and widths of observed low-field NMR resonances enable the study of processes affecting spin dynamics. An excellent agreement between simulations and measurements of the spectra, particularly in the largest frequency J-couplings range ever reported in zero-field NMR, is demonstrated.


Croup: an 11-year study in a pediatric practice.
The etiology and epidemiology of croup were studied in a pediatric group practice over an 11-year period, 1964 to 1975. Croup was diagnosed in 951 instances in 6,165 cases of lower respiratory tract infection (LRI) studied. As census figures of the practice clientele were available, attack rates were calculated. The incidence of total LRI was highest in the first year of life. In contrast, the attack rate for croup was highest in the second year of life; the rate declined gradually after that age. Croup was not diagnosed in the first month of life. Boys were 1.43 times more likely to develop croup than were girls. Three hundred sixty agents were isolated from the 951 croup cases. The parainfluenza viruses accounted for 74.2% of all isolates; 65% of the parainfluenza isolates were classified as parainfluenza virus type 1. Respiratory syncytial virus, influenza viruses A and B, and Mycoplasma pneumoniae were the only other agents isolated in appreciable numbers. The propensity of various agents to produce croup symptoms in children with LRI due to specific microorganisms was 58% for parainfluenzae type 1,60% for parainfluenzae type 2, and 29% for parainfluenzae type 3; similar figures for the other agents varied from 5% to 16%. The role of the various agents in the etiology of croup varied with patient age and depended on the propensity of the agent to produce the croup syndrome and the frequency of isolation of the agent at that age. The parainfluenza viruses were the most important croup agents at all ages; respiratory syncytial virus caused croup in children less than 5 years of age whereas the influenza viruses and M pneumoniae were significant causes of croup only in children more than 5 to 6 years old. Croup occurred predominately in late fall and early winter, times when the parainfluenza viruses, especially type 1, occurred most frequently. The epidemiology of croup differs from that of bronchiolitis, pneumonia, and tracheobronchitis; knowledge of this should be helpful to the clinician caring for children with LRI.


Direct synthesis of amides from nonactivated carboxylic acids using urea as nitrogen source and Mg(NO3)2 or imidazole as catalysts.
A new method for the direct synthesis of primary and secondary amides from carboxylic acids is described using Mg(NO3)2·6H2O or imidazole as a low-cost and readily available catalyst, and urea as a stable, and easy to manipulate nitrogen source. This methodology is particularly useful for the direct synthesis of primary and methyl amides avoiding the use of ammonia and methylamine gas which can be tedious to manipulate. Furthermore, the transformation does not require the employment of coupling or activating agents which are commonly required.


Endophthalmitis after pars plana vitrectomy: results of the Pan American Collaborative Retina Study Group.
To determine the incidence of endophthalmitis after 20-, 23-, and 25-gauge pars plana vitrectomies (PPVs). Retrospective comparative case series of consecutive patients who underwent 20-, 23-, or 25-gauge PPV at 11 centers from Latin America between 2005 to 2009. Pars plana vitrectomy cases were identified through a search of the billing records of each institution. Cases of PPV performed in the management of trauma, endophthalmitis, and combined PPV phacoemulsification cases were excluded. Endophthalmitis was diagnosed by clinical criteria regardless of the microbiologic results. The incidence of post-PPV endophthalmitis was compared between 20-, 23-, and 25-gauge PPVs. A total of 35,427 cases of PPV were identified during the study period (n = 19,865 for 20 gauge, n = 10,845 for 23 gauge, and n = 4,717 for 25 gauge). The 5-year post-PPV endophthalmitis incidence rates were 0.020% (4 of 19,865), 0.028% (3 of 10,845), and 0.021% (1 of 4,717) for 20 gauge, 23 gauge, and 25 gauge, respectively (P = 0.9685). Small-gauge transconjunctival PPV does not appear to increase the rates of post-PPV endophthalmitis.


Intranasal Morphology Transformation Nanomedicines for Long-Term Intervention of Allergic Rhinitis.
Intranasal administration has been widely explored as a potential treatment for allergic rhinitis, and improving intranasal penetration and retention of drugs is a challenging requirement to further improve efficacy. Delivery strategies of nanocarriers that enhance mucosal adhesion or mucus penetration have been proposed to improve nasal drug delivery; however, delivery efficiency remains limited by excessive pulmonary deposition and nonspecific cell phagocytosis. In this work, a "nasal in situ assembly" strategy was presented to construct intranasal morphology transformation nanomedicines with enhanced effective drug concentration for long-term intervention of allergic rhinitis. The polymer-polypeptide nanomedicine (PHCK) with a CCR3 antagonistic peptide (C) and a pH-responsive polyethylene glycol (H) was developed, encapsulating ketotifen (KT). PHCK nanoparticles displayed nasal mucosa permeability and transformed to nanofibers in the acidic environment of the nasal cavity, realizing responsive burst release of KT simultaneously. The fibrotic reassembly reduced the cellular internalization of nanomedicine and increased the CCR3 blockade on the eosinophil (EOS) membranes. Both in vitro and in vivo data indicated that PHCK achieved improved drug accumulation and retention in the nasal cavity and decreased pulmonary deposition, then effectively inhibited mast cell degranulation and EOS chemotaxis. This study demonstrates that the "nasal in situ assembly" strategy can improve drug delivery efficiency upon nasal responsive morphologic transformation, providing exploratory perspectives for nasal delivery platforms establishment and boosting therapeutic effect of allergic rhinitis.


Ultrasound in Aesthetics: Filler and Non-Filler Applications.
Ultrasound in aesthetics presents multiple applications in several areas, including diagnosing fillers and non-fillers complications, the performance of ultrasound-guided injections in real-time, and identifying the most common types of cosmetic fillers. Furthermore, this application of ultrasound in aesthetics has become a must for managing aesthetic patients because, to date, this modality is the one that provides the higher resolution among imaging techniques, detailed anatomical information, and blood flow detection, besides showing worldwide availability. This paper aims to review the current applications of ultrasound in aesthetics based on publications from scientific literature and the authors' experience.


Small molecule targeting NaV1.7 via inhibition of the CRMP2-Ubc9 interaction reduces and prevents pain chronification in a mouse model of oxaliplatin-induced neuropathic pain.
Treatment with anti-neoplastic agents can lead to the development of chemotherapy induced peripheral neuropathy (CIPN), which is long lasting and often refractory to treatment. This neuropathic pain develops along dermatomes innervated by peripheral nerves with cell bodies located in the dorsal root ganglia (DRG). The voltage-gated sodium channel NaV1.7 is expressed at high levels in peripheral nerve tissues and has been implicated in the development of CIPN. Efforts to develop novel analgesics directly inhibiting NaV1.7 have been unsuccessful, and our group has pioneered an alternative approach based on indirect modulation of channel trafficking by the accessory protein collapsin response mediator protein 2 (CRMP2). We have recently reported a small molecule, compound 194, that inhibits CRMP2 SUMOylation by the E2 SUMO-conjugating enzyme Ubc9 (Cai et al. , Sci. Transl. Med. 2021 13(6 1 9):eabh1314). Compound 194 is a potent and selective inhibitor of NaV1.7 currents in DRG neurons and reverses mechanical allodynia in models of surgical, inflammatory, and neuropathic pain, including spared nerve injury and paclitaxelinduced peripheral neuropathy. Here we report that, in addition to its reported effects in rats, 194 also reduces mechanical allodynia in male CD-1 mice treated with platinumcomplex agent oxaliplatin. Importantly, treatment with 194 prevented the development of mechanical allodynia when co-administered with oxaliplatin. No effects were observed on the body weight of animals treated with oxaliplatin or 194 throughout the study period. These findings support the notion that 194 is a robust inhibitor of CIPN that reduces established neuropathic pain and prevents the emergence of neuropathic pain during treatment with multiple anti-neoplastic agents in both mice and rats.


Pharmacologically Counteracting a Phenotypic Difference in Cerebellar GABAA Receptor Response to Alcohol Prevents Excessive Alcohol Consumption in a High Alcohol-Consuming Rodent Genotype.
Cerebellar granule cell GABAA receptor responses to alcohol vary as a function of alcohol consumption phenotype, representing a potential neural mechanism for genetic predilection for alcohol abuse (Kaplan et al., 2013; Mohr et al., 2013). However, there are numerous molecular targets of alcohol in the cerebellum, and it is not known how they interact to affect cerebellar processing during consumption of socially relevant amounts of alcohol. Importantly, direct evidence for a causative role of the cerebellum in alcohol consumption phenotype is lacking. Here we determined that concentrations of alcohol that would be achieved in the blood after consumption of 1-2 standard units (9 mm) suppresses transmission through the cerebellar cortex in low, but not high, alcohol consuming rodent genotypes (DBA/2J and C57BL/6J mice, respectively). This genotype-selective suppression is mediated exclusively by enhancement of granule cell GABAA receptor currents, which only occurs in DBA/2J mice. Simulating the DBA/2J cellular phenotype in C57BL/6J mice by infusing the GABAA receptor agonist, 4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridine-3-ol hydrochloride, into cerebellar lobules IV-VI, in vivo, significantly reduced their alcohol consumption and blood alcohol concentrations achieved. 4,5,6,7-Tetrahydroisoxazolo-[5,4-c]pyridine-3-ol hydrochloride infusions also significantly decreased sucrose consumption, but they did not affect consumption of water or general locomotion. Thus, genetic differences in cerebellar response to alcohol contributes to alcohol consumption phenotype, and targeting the cerebellar GABAA receptor system may be a clinically viable therapeutic strategy for reducing excessive alcohol consumption. Alcohol abuse is a leading cause of preventable death and illness; and although alcohol use disorders are 50%-60% genetically determined, the cellular and molecular mechanisms of such genetic influences are largely unknown. Here we demonstrate that genetic differences in cerebellar granule cell GABAA receptor responses to recreational concentrations of alcohol are the primary determinant of alcohol's impact on cerebellar processing and that pharmacologically modifying such responses alters alcohol consumption. These data highlight the cerebellum as an important neuroanatomical region in alcohol consumption phenotype and as a target for pharmacological treatment of alcohol use disorders. The results also add to the growing list of cognitive/emotional roles of the cerebellum in psychiatric disease and drug abuse.


[Teaching coping strategies to parents of children suffering from cancer using a short film].
This paper studies the usefulness of a short film in teaching strategies for parents of children with cancer to cope with the situation. The short film is based on an analysis of the transcripts from eight sessions of a self-help group. The short film has been evaluated by psychologists working for each of the parent groups belonging to the Federation of parents of children with cancer. Furthermore, the film has been exhibited in group sessions that took place in the Valencia and Alicante branches of ASPANION (Association of Parents with Oncologic Children in the Valencia Region). About 70% of the experts have declared that the film is a valuable resource for teaching useful strategies to parents. The film also improves the group sessions since it addresses a number of issues that had not been addressed before, and it stimulates the participation of, and communication between, parents during the session.


Perceptions of Relatedness with Classroom Peers Promote Adolescents' Behavioral Engagement and Achievement in Secondary School.
Secondary school is a vulnerable time where stagnation or declines in classroom behavioral engagement occur for many students, and peer relationships take on a heightened significance. We examined the implications of adolescents' perceptions of relatedness with classroom peers for their academic learning. Participants were 1084 adolescents (53% female) in 65 middle and high school classrooms. Multilevel cross-lagged path analyses found that adolescents' perceived relatedness with classroom peers subsequently predicted their increased self-reported behavioral engagement in that classroom from fall to winter and again from winter to spring. Higher engagement in spring predicted higher end of year objective achievement test scores after statistical control of prior year test scores. Implications are discussed for increasing classroom peer relatedness to enhance adolescents' achievement.


Tanshinone IIA pretreatment renders free flaps against hypoxic injury through activating Wnt signaling and upregulating stem cell-related biomarkers.
Partial or total flap necrosis after flap transplantation is sometimes clinically encountered in reconstructive surgery, often as a result of a period of hypoxia that exceeds the tolerance of the flap tissue. In this study, we determine whether tanshinone IIA (TSA) pretreatment can protect flap tissue against hypoxic injury and improve its viability. Primary epithelial cells isolated from the dorsal skin of mice were pretreated with TSA for two weeks. Cell counting kit-8 and Trypan Blue assays were carried out to examine the proliferation of TSA-pretreated cells after exposure to cobalt chloride. Then, Polymerase chain reaction and Western blot analysis were used to determine the expression of β-catenin, GSK-3β, SOX2, and OCT4 in TSA-treated cells. In vivo, after mice were pretreated with TSA for two weeks, a reproducible ischemic flap model was implemented, and the area of surviving tissue in the transplanted flaps was measured. Immunohistochemistry was also conducted to examine the related biomarkers mentioned above. Results show that epidermal cells, pretreated with TSA, showed enhanced resistance to hypoxia. Activation of the Wnt signaling pathway in TSA-pretreated cells was characterized by the upregulation of β-catenin and the downregulation of GSK-3β. The expression of SOX2 and OCT4 controlled by Wnt signaling were also found higher in TSA pretreated epithelial cells. In the reproducible ischaemic flap model, pretreatment with TSA enhanced resistance to hypoxia and increased the area of surviving tissue in transplanted flaps. The expression of Wnt signaling pathway components, stem-cell related biomarkers, and CD34, which are involved in the regeneration of blood vessels, was also upregulated in TSA-pretreated flap tissue. The results show that TSA pretreatment protects free flaps against hypoxic injury and increases the area of surviving tissue by activating Wnt signaling and upregulating stem cell-related biomarkers.


Dendritic cells: importance in allergy.
In this review we discuss the role of dendritic cells (DC) in the pathogenesis of allergic contact hypersensitivity (ACH) and atopic disorders, such as asthma and atopic eczema. In ACH patients, DC recognize the invasion of simple chemicals such as haptens, and trigger antigen-specific T cell responses leading to the characteristic histological and clinical changes such as spongiosis and papulovesicular eruptions. During atopic disorders, it is well known that the Th2-deviated immune response plays a crucial role in their pathogenesis. DC provide T cells with antigen and costimulatory signals (signals 1 and 2, respectively), as well as with a polarizing signal (signal 3). When studying ACH, it is important to understand how simple chemicals induce the activation of DC and their migration to the draining lymph nodes where they supply signals 1 and 2 to naive T cells. The mechanisms by which DC induce the Th2-deviated immune response, namely via the Th2-deviated signal 3, are central topics in the pathogenesis of atopic disorders.


Auditory-perceptual evaluation of disordered voice quality: pros, cons and future directions.
Auditory-perceptual evaluation is the most commonly used clinical voice assessment method, and is often considered a gold standard for documentation of voice disorders. This view has arisen for many reasons, including the fact that voice quality is perceptual in nature and that the perceptual characteristics of voice have greater intuitive meaning and shared reality among listeners than do many instrumental measures. Other factors include limitations in the validity and reliability of instrumental methods and lack of agreement as to the most sensitive and specific instrumental measures of voice quality. Perceptual evaluation has, however, been heavily criticised because it is subjective. As a result, listener reliability is not always adequate and auditory-perceptual ratings can be confounded by factors such as the listener's shifting internal standards, listener experience, type of rating scale used and the voice sample being evaluated. This paper discusses these pros and cons of perceptual evaluation, and outlines clinical strategies and research approaches that may lead to improvements in the assessment of voice quality. In particular, clinicians are advised to use multiple methods of voice quality evaluation, and to include both subjective and objective evaluation tools.


Annealed Au-assisted epitaxial growth of si nanowires: control of alignment and density.
The epitaxial growth of 1D nanostructures is of particular interest for future nanoelectronic devices such as vertical field-effect transistors because it directly influences transistor densities and 3D logic or memory architectures. Silicon nanowires (SiNWs) are a particularly important 1D nanomaterial because they possess excellent electronic and optical properties. What is more, the scalable fabrication of vertically aligned SiNW arrays presents an opportunity for improved device applications if suitable properties can be achieved through controlling the alignment and density of SiNWs, yet this is something that has not been reported in the case of SiNWs synthesized from Au films. This work therefore explores the controllable synthesis of vertically aligned SiNWs through the introduction of an annealing process prior to growth via a Au-catalyzed vapor-liquid-solid mechanism. The epitaxial growth of SiNWs was demonstrated to be achievable using SiCl4 as the Si precursor in chemical vapor deposition, whereas the alignment and density of the SiNWs could be controlled by manipulating the annealing time during the formation of Au nanoparticles (AuNPs) from Au films. During the annealing process, gold silicide was observed to form on the interface of the liquid-phase AuNPs, depending on the size of the AuNPs and the annealing time. This work therefore makes a valuable contribution to improving nanowire-based engineering by controlling its alignment and density as well as providing greater insight into the epitaxial growth of 1D nanostructures.


[Tissue engineering: chances and challenges for application in rheumatic diseases].
Current technologies of tissue engineering offer new strategies for the treatment of cartilage and bone defects. Beyond implantation of cell suspensions, second generation products of biomaterial enforced with in vitro preformed tissues are clinically applied. Ongoing research and development focus on differentiation factors and tissue protection. In search for sources of autologous cells which are easier to collect and which may serve for more complex tissues like osteochondral implants, mesenchymal stem cells are investigated. The design of in vitro experiments, which are required for these investigations, has produced tissue engineering technologies, which may serve for pathophysiology research in inflammatory joint diseases and for exploration of treatment strategies. These together with the advances in biological therapies of rheumatic diseases are the basis of new concepts, which promise application of tissue engineering also in inflammatory joint diseases.


Multicopy Tn10 tet plasmids confer sensitivity to induction of tet gene expression.
We inserted the Tn10 tetracycline resistance determinant (tet) into the multicopy plasmid pACYC177, and we examined the phenotype of Escherichia coli K-12 strains harboring these plasmids. In agreement with others, we find that Tn10 tet exhibits a negative gene dosage effect. Strains carrying multicopy Tn10 tet plasmids are 4- to 12-fold less resistant to tetracycline than are strains with a single copy of Tn10 in the bacterial chromosome. In addition, we find that multicopy tet strains are 30- to 100-fold less resistant to the tetracycline derivative 5a,6-anhydrotetracycline than are single-copy tet strains. Multicopy tet strains are, in fact, 10- to 25-fold more sensitive to anhydrotetracycline than are strains that lack tet altogether. The hypersensitivity of multi-copy strains to anhydrotetracycline is correlated with the effectiveness of anhydrotetracycline as an inducer of tet gene expression, rather than its effectiveness as an inhibitor of protein synthesis. Anhydrotetracycline is 50- to 100-fold more effective than tetracycline as an inducer of tetracycline resistance and as an inducer of beta-galactosidase in strains that harbor tet-lac gene fusions. In contrast, anhydrotetracycline appears to be two- to fourfold less effective than tetracycline as an inhibitor of protein synthesis. Both anhydrotetracycline and tetracycline induce synthesis of tet polypeptides in minicells harboring multicopy tet plasmids. Differences between E. coli K-12 backgrounds influence the tetracycline and anhydrotetracycline sensitivity of multicopy strains; ZnCl2 enhances the tetracycline and anhydrotetracycline sensitivity of these strains two- to threefold. We propose that the overexpression of one or more Tn10 tet gene products inhibits the growth of multicopy tet strains and accounts for their relative sensitivity to inducers of tet gene expression.


Towards Superresolution Surface Metrology: Quantum Estimation of Angular and Axial Separations.
We investigate the localization of two incoherent point sources with arbitrary angular and axial separations in the paraxial approximation. By using quantum metrology techniques, we show that a simultaneous estimation of the two separations is achievable by a single quantum measurement, with a precision saturating the ultimate limit stemming from the quantum Cramér-Rao bound. Such a precision is not degraded in the subwavelength regime, thus overcoming the traditional limitations of classical direct imaging derived from Rayleigh's criterion. Our results are qualitatively independent of the point spread function of the imaging system, and quantitatively illustrated in detail for the Gaussian instance. This analysis may have relevant applications in three-dimensional surface measurements.


Overexpression of Platelet-Derived Growth Factor Receptor Α D842V Mutants Prevents Liver Regeneration and Chemically Induced Hepatocarcinogenesis via Inhibition of MET and EGFR.
Platelet-derived growth receptor α (PDGFRα) is a key factor in many pathophysiological processes. The expression level of PDGFRα is significantly elevated in the early stage of liver development and maintained at a lower level in adult normal livers. In this study, we constructed a liver-specific PDGFRαD842 mutant transgenic (TG) mice model to explore the effect of continuous activation of PDGFRα on liver regeneration and hepatocarcinogenesis. 14-day-old TG and wild-type (WT) mice were intraperitoneally injected with diethylnitrosamine (DEN) at a dose of 25 μg/g body weight. Two-month-old male TG and WT mice were subjected to partial hepatectomy (PH). The liver tissues were collected for further analysis at different time points. Overexpression of PDGFRα D842V and its target genes, Akt, c-myc and cyclin D1 in hepatocytes with no overt phenotype versus WT mice were compared. Unexpectedly, a dramatic decrease in hepatocyte proliferation was noted after PH in TG versus WT mice, possibly due to the downregulation of hepatocyte growth factor receptor (MET) and epidermal growth factor receptor (EGFR). No TG mice developed HCC spontaneously after 14 months follow-up. However, TG mice were more resistant to DEN-induced hapatocarcinogenesis at 6, 10, and 12 months of age, showing delayed hepatocyte proliferation and apoptosis, lower tumor incidence, smaller size and fewer number, compared with age-matched WTs, partially through downregulation of MET and EGFR. In conclusion, continuous activation of PDGFRα signaling by expression of PDGFRα D842V does not promote, but inhibit hepatic regeneration and hepatocarcinogenesis, possibly through compensatory downregulation of MET and EGFR.


Time to listen: strategies to improve hospital-based postnatal care.
In Australia and internationally, women report high levels of dissatisfaction with hospital-based postnatal care. To design and implement strategies to improve hospital-based postnatal care at a Sydney metropolitan hospital. This was an Action Research study. In Phase One, midwives considered the literature and participated in group discussions and interviews to determine their perceptions of postnatal care and the factors that facilitate or hinder the provision of quality care. In Phase Two, midwives participated in 12 working group meetings to design strategies to improve care. Several important principles of postnatal care were described, including building a relationship with women, meeting their individual needs, being flexible in approach and providing continuity of care. 'Listening to women', 'being there,' and 'normalising experiences and expectations' were believed to be critical to achieving these principles. A key strategy 'One to One Time' was designed to provide women with an uninterrupted period of time each day with a midwife who was available to listen to their needs and concerns and discuss issues related to their health and that of their baby. Midwives designed and implemented strategies that they believed would improve in-hospital postnatal care.


Characterization of upFc, a fragment of human immunoglobulin G1 produced by pepsin in urea.
The digestion of human IgG1/K myeloma proteins with pepsin in the presence of 8 M-urea produces fragments that differ from those produced by aqueous peptic digestion, and from other characteristic immunoglobulin fragments. Fb'2, the larger urea/pepsin fragment, was previously shown to consist of the constant regions of the light chains, and the CH1 domains and hinge regions of the heavy chains. The smaller fragment, upFc, has now been characterized. After reduction, three peptides were released from fragment upFc. Amino acid sequencing, N- and C-terminal determinations and amino acid compositions have enabled these peptides to be identified as residues Ile-253 to Leu-306, residues Thr-307 to Asp-376 and residues Thr-411 to Gly-446 of the heavy chain. Fragment upFc therefore contains the entire Fc region, beginning at residue Ile-253, except for a 34-residue section from within the CH3-domain disulphide loop. Peptic digestion of IgG1/K proteins in 8M-urea therefore provides a method for isolating from gamma1 heavy chains five homogeneous peptides in good yield, which account for almost the entire constant region. Characterization of fragments Fb'2 and upFc has shown that the action of pepsin in urea is entirely different from that of aqueous pepsin. Two gamma1 heavy chains have been shown to differ in sequence at three positions from the sequence reported for protein Eu.


Modeling glucose disposal in diabetic dogs fed mixed meals.
We have utilized a previously described mathematical model to study glucose disposal in fed, conscious, ambulatory, diabetic dogs. The model was applied to estimate the daily disposition of ingested glucose in the periphery, liver, and urine following a regular mixed meal containing 130 g of carbohydrate. Experimental data was obtained from 11 pancreatectomized animals. Both the portal and peripheral routes were used for intravenous insulin infusion and the daily profiles of peripheral plasma glucose and insulin concentrations measured. Total calories in mixed meals derived from carbohydrates (37%), fat (30%), and protein (30%). When judged according to the root-mean-square differences, agreement was excellent between model-predicted and experimentally observed glucose as well as insulin concentrations. This agreement occurred whether or not, in addition to basal insulin, meal insulin was also given. Using the model, we then predicted in detail the rates of glucose uptake in peripheral tissue, liver, and kidneys. With portally infused insulin resulting in diurnal glycemic normalization, the net daily hepatic glucose balance was physiological, being close to zero. Remarkably, with peripheral insulin infusions there was an unphysiological net negative hepatic glucose balance of 10 g/day.


Phlebotomine sand flies in rural Mayan communities of Southern Mexico: The heterogeneity of the ruralscape increases the entomological risk.
In the Yucatan Peninsula, tropical preserved forests harbor a high diversity of phlebotomine sand fly species, potential vectors of Leishmania. As a result, a significant risk of contracting localized cutaneous leishmaniasis (LCL) is associated with entry into these forest ecosystems. However, with the current trajectory of land use in the region, communities now live within modified landscapes which could increase their risk of contact with vectors. In this study, we characterized the sand fly fauna and its relationship with the characteristics of peridomestic habitats in two rural communities in Yucatan characterized by contrasting records of leishmaniasis. Five human dwellings in each community were randomly selected and the peridomestic landscape was characterized (i.e., type and percentage of land use). For the collection of sand flies, CDC traps were deployed in both the intra and peridomicile. Differences in alpha and beta diversity between communities and ecotopes were estimated considering three separate groups, all species together, zoophilic species, and anthropophilic species. In total, 1, 241 sand flies represented by eight species were collected from November 2021-March 2022. Both communities registered the presence of sand flies in the intra and peridomicile, and females were more abundant than males. However, the greatest diversity of species was recorded in the peridomicile of the community with the highest composition of land uses. Our study demonstrates that the transformation of the forest around the communities favors the abundance and richness of sand flies in the peridomestic environment. We discuss the limitations and implications of our findings regarding the potential risk of the emergence of peri‑rural cycles of leishmaniasis in the region.


Prevention and control of health care-associated infections through improved hand hygiene.
Determined actions are required to address the burden due to health care-associated infections worldwide and improve patient safety. Improving hand hygiene among health care workers is an essential intervention to achieve these goals. The World Health Organization (WHO) First Global Patient Safety Challenge, Clean Care is Safer Care, pledged to tackle the problem of health care-associated infection at its launch in 2005 and has elaborated a comprehensive set of guidelines for use in both developed and developing countries worldwide. The final version of the WHO Guidelines on Hand Hygiene in Health Care was issued in March 2009 and includes recommendations on indications, techniques, and products for hand hygiene. In this review, we discuss the role of hands in the transmission of health care-associated infection, the benefits of improved compliance with hand hygiene, and the recommendations, implementation strategies and tools recommended by WHO. We also stress the need for action to increase the pace with which these recommendations are implemented in facilities across India.


Crowdsourced Tick Image-Informed Updates to U.S. County Records of Three Medically Important Tick Species.
Burgeoning cases of tick-borne disease present a significant public health problem in the United States. Passive tick surveillance gained traction as an effective way to collect epidemiologic data, and in particular, photograph-based tick surveillance can complement in-hand tick specimen identification to amass distribution data and related encounter demographics. We compared the Federal Information Processing Standards (FIPS) code of tick photos submitted to a free public identification service (TickSpotters) from 2014 to 2019 to published nationwide county reports for three tick species of medical concern: Ixodes scapularis Say (Ixodida: Ixodidae), Ixodes pacificus Cooley and Kohls (Ixodida: Ixodidae), and Amblyomma americanum Linneaus (Ixodida: Ixodidae). We tallied the number of TickSpotters submissions for each tick species according to "Reported" or "Established" criteria per county, and found that TickSpotters submissions represented more than half of the reported counties of documented occurrence, and potentially identified hundreds of new counties with the occurrence of these species. We detected the largest number of new county reports of I. scapularis presence in Michigan, North Carolina, and Texas. Tick image submissions revealed potentially nine new counties of occurrence for I. pacificus, and we documented the largest increase in new county reports of A. americanum in Kentucky, Illinois, Indiana, and Ohio. These findings demonstrate the utility of crowdsourced photograph-based tick surveillance as a complement to other tick surveillance strategies in documenting tick distributions on a nationwide scale, its potential for identifying new foci, and its ability to highlight at-risk localities that might benefit from tick-bite prevention education.


Impact of film thickness on the morphology of mesoporous carbon films using organic-organic self-assembly.
Mesoporous polymer and carbon thin films are prepared by the organic-organic self-assembly of an oligomeric phenolic resin with an amphiphilic triblock copolymer template, Pluronic F127. The ratio of resin to template is selected such that a body-centered cubic (Im3m) mesostructure is formed in the bulk. However, well-ordered mesoporous films are not always obtained for thin films (<100 nm), and this behavior is found to be directly correlated with the initial phenolic resin to template ratio. Furthermore, the symmetry of ordered phases is highly dependent on the number of layers of spheres in the film: Monolayers and bilayers are characterized by hexagonal close-packed (HCP) symmetry, while films with approximately 5 layers of spheres exhibit a mixture of HCP and face-centered orthorhombic (FCO) structures. Ultrathick films having more than 30 layers of spheres are similar to the bulk body-centered cubic symmetry with a preferential orientation of the closest-packed (110) plane parallel to the substrate. Film thickness and initial composition of the carbonizable precursors in the template are critical factors in determining the morphology of mesoporous carbon films. These results provide insight into why difficulties have been reported in producing ultrathin ordered mesoporous carbon films using cooperative organic-organic self-assembly.


Oxidative stress in children with obstructive sleep apnea syndrome.
Pediatric obstructive sleep apnea (OSA) is associated with cardiovascular consequences, including accelerated atherosclerosis and endothelial dysfunction. Increased lipid peroxidation, a marker of oxidative stress, has been identified in adults with OSA in a severity-dependent manner, with attenuation following treatment with continuous positive airway pressure therapy. Studies on oxidative stress in children with OSA are sparse and results are inconclusive. The objective of this study was to compare lipid peroxidation in children with OSA to non-OSA children. A prospective cross-sectional study of 26 children with polysomnography-confirmed OSA (oAHI ≥ 5/h TST) was conducted. Thirty age- and body mass index z-score-matched children with primary snoring (PS) served as a comparison group (oAHI ≤ 1/h TST). Fasting blood samples were obtained on the morning following the sleep study. Plasma oxidized low-density lipoprotein (oxLDL) concentrations were measured by enzyme-linked immunosorbent assay. There were no group differences in patient characteristics and their lipid profiles. The mean oxLDL levels of the OSA group were significantly higher than those of the comparison group (53.1 ± 13.0 vs. 45.7 ± 10.0 U/L, respectively, p = 0.02). There was a significant positive correlation between plasma oxLDL and the apnea hypopnea index (r = 0.29, p = 0.03) and between oxLDL and the oxygen desaturation index (r = 0.51, p = 0.003), and a significant negative correlation between SpO2 nadir and oxLDL (r = -0.29, p = 0.03). OSA in children is associated with increased lipid peroxidation in a severity-dependent manner. Lipid peroxidation levels correlate with the degree of intermittent hypoxia.


Measuring blood glucose in neonatal units: how does hemocue compare?
Rapid and reliable determination of blood glucose concentration is essential during the neonatal period to prevent adverse neurodevelopmental outcome from hypoglycaemia. Despite their unreliability, reagent strip methods continue to be used extensively in neonatal nurseries due to their rapidity and convenience. Recently, a new portable laboratory standard technique has been introduced (HemoCue B-Glucose system) for whole blood glucose determination. It is particularly suitable for near-patient testing in neonatal units. This new method, as well as other established methods of whole blood (Yellow Springs Instrument (YSI) and a hexokinase method on Cobas Bio), and plasma (Kodak Ektachem) glucose measurement, were therefore evaluated for their accuracy and concordance of measurements taken in the neonatal period. There were substantial discrepancies among the four methods of glucose measurement with wide limits of agreement between these methods. The glucose concentrations measured by HemoCue and YSI (n = 206), HemoCue and hexokinase (n = 113), HemoCue and plasma glucose on Ektachem (n = 69) and hexokinase and Ektachem (n = 66) were likely to differ by -29 to +61%, -23 to +56%, -36 to +65%, and -19 to +30%, respectively. Even the laboratory methods of blood glucose determination, therefore, can not be used interchangeably. Using a model based approach, the probabilities of "discordant" classification as hypo- or normo-glycaemia were estimated to be 6.8%, 6.5%, and 7.1% between HemoCue and YSI, HemoCue and hexokinase on Cobas Bio, and HemoCue and Ektachem analysers, respectively. In view of these low probabilities of discordant classification with other glucose analysers, the HemoCue system may offer a reasonable compromise between bedside and laboratory blood glucose estimations in neonates.


Minimum Effective Volume of Lidocaine for Ultrasound-Guided Costoclavicular Block.
This dose-finding study aimed to determine the minimum effective volume in 90% of patients (MEV90) of lidocaine 1.5% with epinephrine 5 μg/mL for ultrasound-guided costoclavicular block. Using an in-plane technique and a lateral-to-medial direction, the block needle was positioned in the middle of the 3 cords of the brachial plexus in the costoclavicular space. The entire volume of lidocaine was deposited in this location. Dose assignment was carried out using a biased-coin-design up-and-down sequential method, where the total volume of local anesthetic administered to each patient depended on the response of the previous one. In case of failure, the next subject received a higher volume (defined as the previous volume with an increment of 2.5 mL). If the previous patient had a successful block, the next subject was randomized to a lower volume (defined as the previous volume with a decrement of 2.5 mL), with a probability of b = 0.11, or the same volume, with a probability of 1 - b = 0.89. Success was defined, at 30 minutes, as a minimal score of 14 of 16 points using a sensorimotor composite scale. Patients undergoing surgery of the elbow, forearm, wrist, or hand were prospectively enrolled until 45 successful blocks were obtained. This clinical trial was registered with ClinicalTrials.gov (ID NCT02932670). Fifty-seven patients were included in the study. Using isotonic regression and bootstrap confidence interval, the MEV90 for ultrasound-guided costoclavicular block was estimated to be 34.0 mL (95% confidence interval, 33.4-34.4 mL). All patients with a minimal composite score of 14 points at 30 minutes achieved surgical anesthesia intraoperatively. For ultrasound-guided costoclavicular block, the MEV90 of lidocaine 1.5% with epinephrine 5 μg/mL is 34 mL. Further dose-finding studies are required for other concentrations of lidocaine, other local anesthetic agents, and multiple-injection techniques.


Phasing-in of vitrification into routine practice: why, how, and what.
To evaluate and compare the laboratory and clinical outcomes of vitrification with slow-freezing method for cryopreservation of embryos and blastocysts in an in-vitro fertilisation programme. Retrospective analysis of all the 104 cycles of frozen embryo and blastocyst replacements from 2003 to 2008 and all the 149 cycles with embryos or blastocysts for vitrification from 2006 to 2009. Hospital-based Licensed Assisted Reproduction Treatment Centre in Hong Kong. All participants having frozen embryos or blastocysts transfer from 2003 to 2008. Surplus embryos and blastocysts after fresh transfer were cryopreserved by vitrification method. Cryosurvival rate after freeze-thawing of early cleavage embryos and blastocysts by the two cryopreservation methods of slow-freezing and vitrification, and the pregnancy rate, implantation rate, delivery rate and live-birth rate achieved. Cryosurvival rates of both vitrified blastocysts (79%) and early cleavage-stage embryos (88%) were significantly higher, as compared with the slow-freezing groups (57% and 72% respectively, both P<0.05). Pregnancy rates, delivery rates, and implantation rates were all significantly higher with vitrification regardless of the embryo types. Both implantation and live-birth rates were higher (31%, odds ratio=14 and 27%, odds ratio=11, respectively) per vitrified blastocyst transferred as compared with slow-freezing (both 3%). Vitrification improved clinical outcomes of both frozen embryos and especially blastocyst transfers. It conferred upon both blastocysts and embryos better developmental potential after the vitrify-thaw procedure.