Clinical uses of H reflexes of upper and lower limb muscles.
H reflexes can be recorded from virtually all muscles that have muscle spindles, but reflex reinforcement may be required for the reflex response to be demonstrable. This can allow conduction across proximal nerve segments and most nerve root segments commonly involved by pathology. Stimulus rate is critical in subjects who are at rest. However the reflex attenuation with higher rates is greatly reduced during a background contraction of the test muscle, with only minor changes in latency if any. In addition the contraction ensures that the reflex response occurs in the desired muscle. Reflex latencies should be corrected for height (or limb length) and age. Because the reflex discharge requires a synchronised volley in group Ia afferents, large increases in reflex latency occur rarely with purely sensory lesions. If the H reflex of soleus, quadriceps femoris or flexor carpi radialis is absent at rest but appears during a voluntary contraction at near-normal latency, there is either low central excitability or a predominantly sensory abnormality. With the former H reflexes will be difficult to elicit throughout the body. If H reflexes can be recorded at rest from muscles for which no reflex can normally be demonstrated, there is good evidence for hyperreflexia. In the context of possible ALS, this is an important finding when there is EMG evidence of chronic partial denervation in that muscle.


Urinary soluble CD163 is a good biomarker for renal disease activity in lupus nephritis.
Activated macrophages expressing CD163 (M2) are the most abundant macrophage subtype in renal biopsies from lupus nephritis (LN) patients. We studied the role of proteolytically cleaved soluble CD163 (sCD163) as a biomarker of LN disease activity. SLE patients were classified as active LN (AN), inactive disease (ID), and active non-renal disease (ANR). Urine and plasma samples were collected at baseline from all patients and at 3 monthly follow-up from AN patients. sCD163 was measured by ELISA. Urine values were normalized to urinary creatinine excretion and expressed as pg/mg. Urine samples from 25 healthy controls (HC) and 20 rheumatoid arthritis patients served as disease controls (DC). Among the 122 patients studied (114 females, 57 AN, 42 ID, 23 ANR), baseline median urinary sCD163 in the AN group (114.01 pg/mg) was significantly higher (p < 0.001) as compared with ID (10.34 pg/mg), ANR (3.82 pg/mg), HC (0 pg/mg), and DC (7.56 pg/mg) groups and showed modest correlation with renal SLEDAI (r = 0.47; p < 0.001). Urinary sCD163 performed the best on receiver operating characteristics (ROC) analysis (AUC = 0.76) at baseline to differentiate between AN and ANR as compared with plasma sCD163, anti-ds DNA antibodies, and C3 and C4. In follow-up study, urinary sCD163 decreased significantly (p < 0.001) in AN patients at 3 (22.07 pg/mg), 6 (12.7 pg/mg), 9 (11.09 pg/mg), and 12 months (7.2 pg/mg). In 4 patients who had either relapse or developed CKD, urinary sCD163 levels correlated with the changing disease activity. Urinary sCD163 is a good biomarker of LN disease activity. Key Points • Urinary sCD163 levels are raised in patients with active lupus nephritis and correlate with renal SLEDAI. • Urinary sCD163 levels fall after treatment and may be helpful in monitoring response to therapy in lupus nephritis.


Prevalence of and progression to abnormal noninvasive markers of liver disease (aspartate aminotransferase-to-platelet ratio index and Fibrosis-4) among US HIV-infected youth.
To longitudinally characterize noninvasive markers of liver disease in HIV-infected youth. HIV infection, without viral hepatitis coinfection, may contribute to liver disease. Noninvasive markers of liver disease [FIB-4 (Fibrosis-4) and APRI (aspartate aminotransferase-to-platelet ratio index)] have been evaluated in adults with concomitant HIV and hepatitis C, but are less studied in children. In prospective cohorts of HIV-infected and HIV-uninfected youth, we used linear regression models to compare log-transformed FIB-4 and APRI measures by HIV status based on a single visit at ages 15-20 years. We also longitudinally modeled trends in these measures in HIV-infected youth with two or more visits to compare those with behavioral vs. perinatal HIV infection (PHIV) using mixed effect linear regression, adjusting for age, sex, body mass index, and race/ethnicity. Of 1785 participants, 41% were men, 57% black non-Hispanic, and 27% Hispanic. More HIV-infected than uninfected youth had an APRI score more than 0.5 (13 vs. 3%, P < 0.001). Among 1307 HIV-infected participants with longitudinal measures, FIB-4 scores increased 6% per year (P < 0.001) among all HIV-infected youth, whereas APRI scores increased 2% per year (P = 0.007) only among PHIV youth. The incidence rates (95% confidence interval) of progression of APRI to more than 0.5 and more than 1.5 were 7.5 (6.5-8.7) and 1.4 (1.0-1.9) cases per 100 person-years of follow-up, respectively. The incidence of progression of FIB-4 to more than 1.5 and more than 3.25 were 1.6 (1.2-2.2) and 0.3 (0.2-0.6) cases per 100 person-years, respectively. APRI and FIB-4 scores were higher among HIV-infected youth. Progression to scores suggesting subclinical fibrosis or worse was common.


Chemometric study and analytical enzymatic methods for diagnosis of cholesterol gallstones.
The lithogenic index (IL) provides an estimate of cholesterol saturation in gallbladder bile and is of possible value for prediction of gallstone formation. A package for pattern recognition of analytical chemical data, known as "Parvus", was used to study the different values of IL obtained experimentally using common enzymic methods for cholesterol and bile salts and other analytical techniques for phospholipids. Ten patients were investigated and some interesting conclusions were drawn, both on the equivalence of various analytical methods for the determination of phospholipids and on the contribution of pattern recognition analysis to the diagnosis of gallstones.


Respiratory function in healthy long-term meditators: A cross-sectional comparative study.
Respiratory function is thought to improve with long-term meditation. This study aimed to assess respiratory function in a cohort of healthy long-term meditators and non-meditators in Sri Lanka. Respiratory function of healthy, skilled long-term meditators (n = 20) practicing Buddhist meditation consistently >3 years, and age-sex matched non-meditators (n = 20) were assessed by assessing resting respiratory rate, spirometry, breath-holding time and six-minute-walk distance. Data were analyzed with SPSS-23 statistical software. The long-term meditators; 45% male, mean (SD) total lifetime meditation experience 12.8 (6.5) years, aged 45.8 (8.74) years, BMI 23.68 (2.23) kgm-2, and non-meditators; 45% male, mean (SD) age 45.3 (8.05) years, BMI 23.68 (3.28) kgm-2, were comparable. Long-term meditators had slower resting respiratory rates [mean (SD); 13.35 (1.9) vs. 18.37 (2.31) breaths/minute; p < 0.001], higher peak expiratory flow rates [mean (SD); 9.89 (2.5) vs. 8.22 (2.3) L/s; p = 0.03], and higher inspiratory breath-holding times [mean (SD); 74 (29.84) vs. 53.61 (26.83) seconds, p = 0.038] compared to non-meditators. There was no significant difference in the six-minute-walk distance and estimated maximal oxygen consumption between the two groups.Resting respiratory rate of long-term meditators, showed a significant negative correlation with total lifetime meditation practice in years (r = -0.444, p = 0.049), and the average length of a meditation session per day (r = -0.65, p = 0.002). The long-term meditators with longer duration of retreat participation demonstrated lower resting respiratory rate (r = -0.522, p = 0.018) and higher tidal volumes (r = 0.474, p = 0.04). Long-term meditators had significantly slower resting respiratory rates and longer breath-holding times, with better spirometry parameters than non-meditators. Greater practice duration and retreat experience appear to be associated with improved resting respiratory function in long-term meditators.


Differential effect of silver nanoparticles on the microbiome of adult and developing planaria.
Silver nanoparticles (AgNPs) are widely incorporated in household, consumer and medical products. Their unintentional release via wastewaters raises concerns on their environmental impact, particularly for aquatic organisms and their associated bacterial communities. It is known that the microbiome plays an important role in its host's health and physiology, e.g. by producing essential nutrients and providing protection against pathogens. A thorough understanding of the effects of AgNPs on bacterial communities and on their interactions with the host is crucial to fully assess AgNP toxicity on aquatic organisms. Our results indicate that the microbiome of the invertebrate Schmidtea mediterranea, a freshwater planarian, is affected by AgNP exposure at the tested 10 μg/ml concentration. Using targeted amplification of the bacterial 16S rRNA gene V3-V4 region, two independent experiments on the microbiomes of adult worms revealed a consistent decrease in Betaproteobacteriales after AgNP exposure, mainly attributed to a decrease in Curvibacter and Undibacterium. Although developing tissues and organisms are known to be more sensitive to toxic compounds, three independent experiments in regenerating worms showed a less pronounced effect of AgNP exposure on the microbiome, possibly because underlying bacterial community changes during development mask the AgNP induced effect. The presence of a polyvinyl-pyrrolidone (PVP) coating did not significantly alter the outcome of the experiments compared to those with uncoated particles. The observed variation between the different experiments underlines the highly variable nature of microbiomes and emphasises the need to repeat microbiome experiments, within and between physiological states of the animal.


Diversity of the apoptotic response to chemotherapy in childhood leukemia.
Apoptosis is the primary mechanism through which most chemotherapeutic agents induce tumor cell death. The purpose of this study was to determine the extent to which blasts from children with leukemia undergo a uniform apoptotic death pathway in vivo. The expression of pro- and anti-apoptotic proteins p53, p21, MDM-2, BCL-2, BCL-X(L), BCL-X(S), and BAX, and caspase-3 activity was determined in circulating blasts collected from the peripheral blood of children with leukemia prior to, and at serial time points following chemotherapy. Culturing blasts ex vivo for 12 h assessed spontaneous apoptosis and the increment induced by chemotherapy. Baseline apoptosis varied between 3% and 29%. Twenty-four hours following chemotherapy the increase in the percentage of cells undergoing apoptosis ranged from <1% to 38%. Eleven of 20 patients who received initial treatment with a p53-dependent drug showed an increase in p53 expression. In these patients, the levels of p53 target genes were also increased. A uniform pattern of BCL-2 family protein expression was not observed and only a minority of samples showed a change that would favor apoptosis. We conclude that that the initial apoptotic response to chemotherapy in children with leukemia is variable involving both p53-dependent and p53-independent pathways.


Occurrence of sepiapterin deaminase in the normal type silkworm, Bombyx mori.
Sepiapterin deaminase was prepared from the normal strain of the silkworm, Bombyx mori. After inhibition experiments, this enzyme was found to have the same properties as that isolated from the lemon mutant strain. Several new inhibitors and their Ki values are described for the deaminase.


Isolation of three types of Gi from bovine spleen.
We have previously reported the purification of two alpha subunits of G proteins, Gi2 and Gi3, from bovine spleen. However, it recently became clear that the preparation of Gi3 alpha contained a significant amount of Gi1 alpha by the immunoblot analysis using specific antibodies. In this study, we purified these G proteins as a trimer form from bovine spleen, and obtained following results. (1) Gi3 was separated from Gi1 using Mono Q column chromatography. Isoelectric focusing was employed to distinguish Gi3 from Gi1 in the column eluates. (2) Purified Gi2 and Gi3 retained much higher activities to bind GTP gamma S or to be ADP-ribosylated by pertussis toxin than the alpha subunits purified previously. (3) Using these spleen Gi2 and Gi3 and bovine brain Gi1, the parameter of GTP gamma S binding to the three types of Gi was compared. Three Gis showed different rates of GTP gamma S binding but showed the similar Kd values.


A prevalence study of multiple sclerosis in L'Aquila, central Italy.
We report the results of an epidemiologic study in the Municipality of L'Aquila, Abruzzo, Central Italy, undertaken to estimate the prevalence rate of Multiple Sclerosis (MS). On December 31, 1984, the prevalence was 33.2 per 100,000 (34.2 when age and sex is standardized to the Italian population). In agreement with recent intensive surveys from different regions in the North and South of Italy, our data indicate that the prevalence of MS in Italy is higher than 30 per 100,000, and emphasize the importance of small population studies in the epidemiology of MS. Our findings suggest that in Italy the risk for MS is higher than recorded before.


Comparing nasopharyngeal apnoeic oxygenation at 18 l/min to preoxygenation alone in obese patients - A randomised controlled study.
Investigate a low-cost, nasopharyngeal apnoeic oxygenation technique, establish its efficacy, and compare it to preoxygenation only in an obese population. The study's hypothesis was that nasopharyngeal apnoeic oxygenation at 18 l.min-1 would significantly prolong safe apnoea time compared to preoxygenation alone. Randomised controlled study. Theatre complex of a resource constrained hospital. 30 adult, obese (BMI ≥ 35 kg.m-2) patients presenting for elective surgery. Patients with limiting cardio-respiratory disease, suspected difficult airway, risk of aspiration, and that were pregnant, were excluded. Patients were allocated by block randomisation in a 1:2 ratio to a preoxygenation-only (No-AO) and an intervention group (NPA-O2). All patients were preoxygenated to an Et-O2 > 80%, followed by a standardised induction. The intervention group received oxygen at 18 l.min-1 via the nasopharyngeal catheter intervention. The desaturation process was documented until an SpO2 of 92% or 600 s was reached. Baseline demographic and clinical characteristics were collected. The primary outcome was safe apnoea time, defined as the time taken to desaturate to an SpO2 of 92%. Secondary outcomes were rate of carbon dioxide accumulation and factors affecting the risk of desaturation. The study was conducted in a morbidly obese population (NoAO = 41,1 kg.m-2; NPA-O2 = 42,5 kg.m-2). The risk of desaturation was signifantly lower in the intervention group (Hazzard Ratio = 0,072, 95% CI[0,019-0,283]) (Log-Rank test, p < 0.001). The median safe apnoea time was significantly longer in the intervention group (NoAO = 262 s [IQR 190-316]; NPA-O2 = 600 s [IQR 600-600]) (Mann-Whitney-U test, p < 0.001). The mean rate of CO2 accumalation was significantly slower in the intervention group (NoAO = 0,47 ± 0,14 kPa.min-1; NPA-O2 = 0,3 ± 0,09 kPa.min-1) (t-test, p = 0.003). There were no statistically significant risk factors associated with an increased risk of desaturation found. Nasopharyngeal apnoeic oxygenation at 18 l/min prolongs safe apnoea time, compared to preoxygenation alone, and reduces the risk of desaturation in morbidly obese patients. PACTR202202665252087; WC/202004/007.


Epithelial to mesenchymal transition in head and neck squamous carcinoma: association of Src activation with E-cadherin down-regulation, vimentin expression, and aggressive tumor features.
Epithelial-mesenchymal transformations (EMT) are critical for the invasion, progression, and metastasis of epithelial carcinogenesis. The role of EMT in head and neck squamous carcinoma (HNSC) tumorigenesis remains unexplored. In the current study, the expressions of several factors associated with the induction of EMT in HNSC cell lines and tumor specimens were investigated to define their functional and pathologic role in HNSC. Eleven HNSC cell lines and 50 primary tumor tissue specimens formed the materials of this study. Western blot analysis as well as immunohistochemical, and functional techniques were used to assess the status of activated Src (p-Src), E-cadherin, and vimentin in both cell lines and tumor tissues and the results were correlated with patients' clinicopathologic parameters. The results demonstrated the inverse expression of p-Src and E-cadherin in the majority of cell lines and in primary tumor tissues compared with normal squamous mucosa. Elevated levels of p-Src were accompanied by down-regulation of E-cadherin and the expression of vimentin in epithelial tumor cells. In vitro inhibition of Src led to E-cadherin reexpression and increased cell contact in squamous carcinoma cell lines. Immunophenotypic analysis of these markers in primary tumor tissues demonstrated a significant correlation between increased p-Src, decreased E-cadherin, and vimentin expression and aggressive tumor features including penetrating invasive fronts, high-grade sarcomatoid transformation, and lymph node metastasis. The results of the current study indicate that Src and E-cadherin may play an important role in EMT, invasion, and aggressive clinicopathologic features of HNSC. These proteins may be targeted for the therapeutic intervention of patients with HNSC.


A dissociation of conscious visual imagery and visual short-term memory.
Two people who reported an impaired ability to form conscious visual images were tested. Compared to a control group of college students, these impaired visualizers were not impaired on two tests of visual short-term memory. Furthermore, they retained more digits in visual short-term memory than they could visualize. These results suggests that deficits in the ability to form conscious visual images can arise without visual short-term memory being impaired, and conscious visual imagery should not be equated with visual short-term memory.


Mechanisms Underpinning Increased Plasma Creatinine Levels in Patients Receiving Vemurafenib for Advanced Melanoma.
Serum creatinine has been reported to increase in patients receiving Vemurafenib, yet neither the prevalence nor the mechanism of this adverse event are known. We aimed to evaluate the frequency and the mechanisms of increases in plasma creatinine level in patients receiving Vemurafenib for advanced melanoma. We performed a retrospective monocentric study including consecutive patients treated with Vemurafenib for an advanced melanoma. We collected clinical and biological data concerning renal function before introduction of Vemurafenib and in the course of monthly follow-up visits from March 2013 to December 2014. Cystatin C-derived glomerular filtration rate was evaluated before and after Vemurafenib initiation, as increase in serum cystatin C is specific to a decrease in the glomerular filtration rate. We also performed thorough renal explorations in 3 patients, with measurement of tubular secretion of creatinine before and after Vemurafenib initiation and a renal biopsy in 2 patients. 70 patients were included: 97% of them displayed an immediate, and thereafter stable, increase in creatinine (+22.8%) after Vemurafenib initiation. In 44/52 patients in whom Vemurafenib was discontinued, creatinine levels returned to baseline. Serum cystatin C increased, although proportionally less than serum creatinine, showing that creatinine increase under vemurafenib was indeed partly due to a renal function impairment. In addition, renal explorations demonstrated that Vemurafenib induced an inhibition of creatinine tubular secretion. Thus, Vemurafenib induces a dual mechanism of increase in plasma creatinine with both an inhibition of creatinine tubular secretion and slight renal function impairment. However, this side effect is mostly reversible when Vemurafenib is discontinued, and should not lead physicians to discontinue the treatment if it is effective.


Mutational analysis of F-pilin reveals domains for pilus assembly, phage infection and DNA transfer.
The F-pilus has been implicated in recipient cell recognition during the establishment of a stable mating pair before conjugation as well as forming part of the conjugative pore for DNA transfer. The F-pilus is the site of attachment of the filamentous phages (M13, f1 and fd), which attach to the F-pilus tip, and the RNA phages, R17 and Qbeta, which attach to different sites exposed on the sides of the pilus. R17 has been shown to undergo eclipse, or capsid release, outside the cell on pili attached to cells. New and existing mutants of traA combined with natural variants of F-pilin were assayed for pilin stability and processing, pilus elongation, transfer, phage sensitivity and R17 eclipse. Phenotypes of these mutants indicated that the F-pilin subunit contains specific regions that can be associated with pilus assembly, phage sensitivity and DNA transport. Mutations involving lysines and phenylalanines within residues 45-60 suggest that these residues might participate in transmitting a signal down the length of the pilus that initiates DNA transfer or R17 eclipse.


Multidimensional futuristic approaches to address the pandemics beyond COVID-19.
Globally, the impact of the coronavirus disease 2019 (COVID-19) pandemic has been enormous and unrelenting with ∼6.9 million deaths and ∼765 million infections. This review mainly focuses on the recent advances and potentially novel molecular tools for viral diagnostics and therapeutics with far-reaching implications in managing the future pandemics. In addition to briefly highlighting the existing and recent methods of viral diagnostics, we propose a couple of potentially novel non-PCR-based methods for rapid, cost-effective, and single-step detection of nucleic acids of viruses using RNA mimics of green fluorescent protein (GFP) and nuclease-based approaches. We also highlight key innovations in miniaturized Lab-on-Chip (LoC) devices, which in combination with cyber-physical systems, could serve as ideal futuristic platforms for viral diagnosis and disease management. We also discuss underexplored and underutilized antiviral strategies, including ribozyme-mediated RNA-cleaving tools for targeting viral RNA, and recent advances in plant-based platforms for rapid, low-cost, and large-scale production and oral delivery of antiviral agents/vaccines. Lastly, we propose repurposing of the existing vaccines for newer applications with a major emphasis on Bacillus Calmette-Guérin (BCG)-based vaccine engineering.


Severe COVID-19, multisystem inflammatory syndrome in children, and Kawasaki disease: immunological mechanisms, clinical manifestations and management.
Multisystem inflammatory syndrome (MIS-C) is a pediatric hyperinflammation disorder caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It has now been reported from several countries the world over. Some of the clinical manifestations of MIS-C mimic Kawasaki disease (KD) shock syndrome. MIS-C develops 4-6 weeks following SARS-CoV-2 infection, and is presumably initiated by adaptive immune response. Though it has multisystem involvement, it is the cardiovascular manifestations that are most prominent. High titres of anti-SARS-CoV-2 antibodies are seen in these patients. As this is a new disease entity, its immunopathogenesis is not fully elucidated. Whether it has some overlap with KD is still unclear. Current treatment guidelines recommend use of intravenous immunoglobulin and high-dose corticosteroids as first-line treatment. Mortality rates of MIS-C are lower compared to adult forms of severe COVID-19 disease.


Tessier sequential extraction on 17 elements from three marine sediment certified reference materials (HISS-1, MESS-4, and PACS-3).
The four-step Tessier sequential extraction procedure is a well-known approach used for environmental and geochemical studies in soil and sediments. However, a lack of reference materials limits its use making implementation and quality control cumbersome. This study applied Tessier sequential extraction to three globally used marine sediment certified reference materials (CRMs) including HISS-1, MESS-4, and PACS-3 with varying levels of contamination. The study analyzed the distribution of 17 elements throughout the extraction phases. Overall, the percent recovery (sum of steps vs total metal concentration) of all analyzed elements in Tessier extraction was 92% + 40% in HISS-1, 101% + 12% in MESS-4, and 102% + 10% in PACS-3. The observed uncertainty of the individual elemental concentrations averaged at 13%, which compares favorably with the 16% target uncertainty derived from the Horwitz equation. The reference data set produced here using the Tessier sequential extraction procedure will serve as a quality control and method development tool for laboratories. Graphical abstract.


Have a Date With Surgery? PROMs Help Patients Decide.
Patient-reported outcomes measures (PROMs) use a patient's response to questions to measure health status. If they're going to catch on payers will need to incentivize use. So far, that's not happening. But clinicians who use PROMs for clinical decision making might be providing a valuable service.


Scanning electron microscopy of the bile ductule.
Scanning electron microscopy of a liver biopsy specimen from a patient 6 months after the onset of acute hepatitis revealed a normal appearing bile ductule. The bile ductule was 13 micron in outer diameter and 1.5-2.7 micron in inner diameter. The ductular lumen was surrounded by two ductular cells and ampullary dilated at the canalicular side. In the lumen, intracytoplasmic diverticles were observed with an orifice diameter of 0.9 micron. About 15 microvilli 0.4-0.6 micron in length and 0.1 micron in thickness were observed on 1 micron2 of luminal surface. The number of microvilli was calculated to be approximately 1,500 per ductular cell. A single cilium 0.15 micron in diameter at the base and 0.10 micron at the trunk, and 7-15 micron in length was found on each ductular cell. The cilium arose from a recess at the canalicular side of the ductular cell, and the free-end was on the bile-duct side. The cilia seemed to play an important role in bile flow to the duct. Sometimes between the ductular cells at the edge of the basal portion a cell was intercalated with thin processes. Such thin processes were not observed on ductular cells.


Combined Association of Novel and Traditional Inflammatory Biomarkers With Carotid Artery Plaque: GlycA Versus C-Reactive Protein (ELSA-Brasil).
Elevated levels of glycoprotein acetylation (GlycA) and C-reactive protein (CRP) have been associated with carotid artery plaque (CAP). However, it is not yet established if elevations in both inflammatory biomarkers provide incremental association with CAP. This study aimed evaluate the cross-sectional association of high CRP and GlycA with CAP at baseline participants from the ELSA-Brasil adult cohort. Participants with information on CRP, GlycA, and CAP with neither previous cardiovascular disease nor CRP >10 mg/L were included. High GlycA and CRP were defined as values within upper quintile and >3 mg/L, respectively. Participants were classified into 4 groups: 1. nonelevated CRP/GlycA (reference group); 2. elevated CRP alone; 3. elevated GlycA alone; and 4. both elevated. The analysis included 4,126 participants with median age of 50 years-old, being 54.2% of women. Prevalence of CAP was 36.1%. Participants with high CRP had the highest frequency of obesity, whereas participants with high GlycA presented higher cardiovascular risk factor burden and were more likely to have CAP than the reference group (odds ratio [OR] 1.39, 95% confidence interval [CI] 1.11 to 1.73), persisting after multivariable adjustment (OR 1.37, 95% CI 1.02 to 1.83). Participants with both elevated CRP and GlycA were more likely to have CAP in crude (OR 1.35, 95% CI 1.10 to 1.65) but not in adjusted models. The findings suggest potential different biologic pathways between inflammation and carotid atherosclerosis: high GlycA was associated with CAP whereas high CRP was more associated with obesity.


Ribosomal Profiling by Gradient Fractionation of Cell Lysates.
Ribosomal profiling is a widely used technique for deep sequencing of ribosome-protected mRNA and for measuring ribosome status in cells. It is a powerful method that is typically employed for monitoring and measuring protein translation status and ribosome activity. Also, it has been used for monitoring the ribosomal stress-responsive events in the ribosome activity. Furthermore, this approach enables understanding of translational regulation, which is invisible in most proteomic approaches. Moreover, this method is known as an important approach for biological discovery such as identification of translation products. Hence, this methodology will be useful for studying cellular events engaging in ribosome assembly, ribosome biogenesis, ribosome activity, translation during the cell cycle, cell proliferation, and growth as well as the ribosomal stress response in mammalian cells.


Rate of development of oesophagogastric parakeratosis in the growing pig: some effects of finely ground barley diets, genotype and previous husbandry.
The rate of development of parakeratotic lesions in the gastric pars oesophagea was investigated in three experiments using 360 pigs, initially aged 10 to 11 weeks and weighing about 30 kg, of differing genotype and with some differences in previous rearing method, given a diet based on finely ground barley which was known to predispose to lesion formation. Lesions were found in some pigs at 10 to 11 weeks old but the incidence and severity increased progressively indicating development as quickly as one month after first giving the finely ground diet. There were indications that different genotypes and different diets given previously in rearing may have influenced the results obtained. The possible influence of other environmental factors is discussed.


Spatial analysis of COVID-19 clusters and contextual factors in New York City.
Identifying areas with low access to testing and high case burden is necessary to understand risk and allocate resources in the COVID-19 pandemic. Using zip code level data for New York City, we analyzed testing rates, positivity rates, and proportion positive. A spatial scan statistic identified clusters of high and low testing rates, high positivity rates, and high proportion positive. Boxplots and Pearson correlations determined associations between outcomes, clusters, and contextual factors. Clusters with less testing and low proportion positive tests had higher income, education, and white population, whereas clusters with high testing rates and high proportion positive tests were disproportionately black and without health insurance. Correlations showed inverse associations of white race, education, and income with proportion positive tests, and positive associations with black race, Hispanic ethnicity, and poverty. We recommend testing and health care resources be directed to eastern Brooklyn, which has low testing and high proportion positives.


Hysteresis in accommodation.
Under certain conditions the accommodative response is not a simple function of accommodative stimulus, but depends as well upon the history of the stimulus. Experimental evidence points to multiple mode control of accommodation as being responsive: a high-gain feedback control mode responds to blur; a second mode causes a drift to bias set level when visual stimuli are removed. We extend a model consistent with these results and use it to predict the results of a new experimental paradigm, 'pushdown' accommodation. Finally, we extend the model to a third mode of behaviour, schematic accommodation, which encompasses instrument myopia, proximal accommodation and voluntary accommodation.


Iron oxides in novel skin care formulations attenuate blue light for enhanced protection against skin damage.
Ultraviolet (UV) radiation is a main cause of aging of sun-exposed skin, but greater attention is being focused on the damaging effects of high-energy visible (HEV) light (400 and 500 nm). HEV light exposure has increased with expanding use of consumer electronics, such as smartphones, which have a peak emission in the 400-490 nm range. Sunscreens containing titanium dioxide and zinc oxide protect against UVA and UVB radiation but provide limited protection against HEV light. Iron oxides including red iron oxide (Fe2 O3 ), yellow iron oxide (Fe(OH)3 /FeOOH), and black iron oxide (Fe3 O4 ) effectively block HEV light, each with a different attenuation profile. Zinc oxide, titanium dioxide, and iron oxides with patented skin care ingredients have been incorporated into several formulations to provide enhanced skin protection (Colorescience, Inc). The percent of HEV light attenuation from 400 nm to 490 nm light was measured in vitro using a technique known as diffuse transmittance spectroscopy using a Perkin Elmer Lambda™ 750 UV/Vis/NIR Spectrophotometer equipped with a 100-mm integrating Labsphere® and PbS detector. Products formulated with zinc oxide, titanium dioxide, and iron oxides demonstrated 71.9%-85.6% attenuation across the tested wavelengths of 415-465 nm. Sunscreens formulated with iron oxides provide enhanced protection against blue light, especially when combined with zinc oxide. To our knowledge, similar studies with iron oxides have not been performed.


Urethral diverticulum with urethrocutaneous fistula and giant stone: A case report.
Male urethral diverticulum is rare and usually associated with urethral obstruction. We report a 62-year-old male presented to emergency room with giant stone coming from scrotum without urinary retention. From clinical findings, a giant stone obviously burst out from his scrotal fistula. Pelvic computed tomography confirmed urethral diverticulum containing a giant stone with multiple smaller stones. Cystourethroscopy was performed to assess diverticulum and luminal obstruction, and no obstruction was found. We performed stones extirpation, diverticulectomy, and urethroplasty consecutively. Intraoperative findings confirmed preoperative detection. Complete stone-free rate and diverticulum removal were successfully accomplished. The patient was discharged postoperatively at day 7.


Overweight during childhood and internalizing symptoms in early adolescence: The mediating role of peer victimization and the desire to be thinner.
Overweight is associated with depression and anxiety among adults. It is unclear whether this association begins in childhood. Overweight among children is associated with a higher risk of peer victimization, and may mediate an association between overweight and internalizing symptoms. No study has tested this hypothesis in a longitudinal population-based sample using developmental trajectories of overweight in middle childhood. Data was drawn from the population-based Quebec Longitudinal Study of Child Development. A three-group trajectory model of overweight development (6-12 years) was previously identified using a semi-parametric group-based approach (n=1678): "early-onset" (11.0%), "late-onset" (16.6%) and "never overweight" (72.5%). Mediation models tested the link between overweight status and child-reported depression and anxiety at 13 years via peer victimization and body dissatisfaction. Children on an early-onset overweight trajectory were at increased risk for both depression (B=.318, 95% CI=.141;.496) and anxiety (B=.262, 95% CI=.09;.44) at 13 years. These direct associations were mediated by peer victimization and subsequent desire to be thinner. Children on a late-onset childhood overweight trajectory were at increased risk for both depression (B=.332, 95% CI=.187;.477) and anxiety (B=.215; 95% CI=.072;.358) at 13 years, mediated by the desire to be thinner. We were unable to control for previous levels of body dissatisfaction. Our measure of peer victimization was not specific to weight-based teasing. Overweight during middle childhood increases risk of early adolescence internalizing symptoms. Peer victimization and body dissatisfaction are partly responsible for this link.


IFT80 is essential for chondrocyte differentiation by regulating Hedgehog and Wnt signaling pathways.
Partial mutation of intraflagellar transport 80 (IFT80) in humans causes Jeune asphyxiating thoracic dystrophy (JATD) and short-rib polydactyly (SRP) syndrome type III. These diseases are autosomal recessive chondrodysplasias that share clinical similarities, including shortened long bones and constricted thoracic cage. However, the role and mechanism of IFT80 in the regulation of chondrocyte differentiation and function remain largely unknown. We hypothesize that IFT80 is required for the formation and function of cilia and plays a critical role in chondrogenic differentiation by regulating Hedgehog (Hh) and Wingless (Wnt) signaling pathways. To test this hypothesis, we first analyzed the IFT80 expression pattern and found that IFT80 was predominantly expressed in growth plate chondrocytes and during chondrogenic differentiation. Silencing IFT80 impaired cilia formation and chondrogenic differentiation in mouse bone marrow derived stromal cells (BMSCs), and decreased the expression of chondrocyte marker genes--collagen II and aggrecan. Additionally, silencing IFT80 down-regulated Hh signaling activity whereas up-regulated Wnt signaling activity. The overexpression of Gli2 in IFT80-silenced cells promoted chondrogenesis and recovered the chondrogenic deficiency from IFT80 silencing. Overall, our results demonstrate that IFT80 is essential for chondrocyte differentiation by regulating the Hh and Wnt signaling pathways.


Heterogeneity of asthma with nasal polyposis phenotypes: A cluster analysis.
Chronic rhinosinusitis with nasal polyposis (CRSwNP) affects a significant number of asthmatic patients and is notably associated with a more difficult-to-control asthma and marked inflammation. We need more studies on this specific asthma phenotype and its possible subphenotypes, in order to better individualize treatments. The aim of this study is to identify and characterize subphenotypes of asthma patients with CRSwNP using clinical, physiological and inflammatory variables. K-means cluster analysis was performed on 17 clinical, physiological, and inflammatory variables from 1263 patients of all asthma severity and on a subpopulation of patients with asthma and CRSwNP. Study was registered on ClinicalTrials.gov (NCT03694847). On the overall population, three groups were identified. Cluster T1 (n = 708) are young, have a short asthma duration and a low prevalence of CRSwNP. Cluster T2 (n = 263) have the longest asthma duration and Cluster T3 (n = 292) are older with the shortest asthma duration. Patients in Clusters T2 and T3 have similar prevalences of CRSwNP. On the subpopulation of asthma with CRSwNP, three clusters were also identified. Cluster S1 (n = 83) have mild-to-moderate asthma with normal lung function. Clusters S2 (N = 53) and S3 (N = 42) include patients with severe asthma and decreased lung function, but those in Cluster S2 have a longer asthma duration, whereas those Cluster S3 have late-onset asthma. Despite coexistence of asthma and CRSwNP, not all patients have the same evolution of their asthma. Different phenotypes of asthma with CRSwNP can be identified and exploration of the characteristics of these subgroups could lead to a better individualized, targeted management.


Febrile infection-related epilepsy syndrome is not caused by SCN1A mutations.
Two distinctive epileptic encephalopathies, febrile infection-related epilepsy syndrome (FIRES) and Dravet syndrome (DS), present with febrile status epilepticus in a normal child followed by refractory focal seizures and cognitive decline although there are differentiating features. Abnormalities of the sodium channel gene SCN1A are found in 75% of DS patients. We found no SCN1A mutations or copy number variants in 10 patients with FIRES. Other genetic etiologies deserve consideration.


Structural Insight into Fungal Cell Wall Recognition by a CVNH Protein with a Single LysM Domain.
MGG_03307 is a lectin isolated from Magnaporte oryzae, a fungus that causes devastating rice blast disease. Its function is associated with protecting M. oryzae from the host immune response in plants. To provide the structural basis of how MGG_03307 protects the fungus, crystal structures of its CVNH-LysM module were determined in the absence and presence of GlcNAc-containing cell wall chitin constituents, which can act as pathogen-associated molecular patterns. Our structures revealed that glycan binding is accompanied by a notable conformational change in the LysM domain and that GlcNAc3 and GlcNAc4 are accommodated similarly. GlcNAc5 and GlcNAc6 interact with the LysM domain in multiple conformations, as evidenced by solution nuclear magnetic resonance studies. No dimerization of MoCVNH3 via its LysM domain was observed upon binding to GlcNAc6, unlike in multiple LysM domain-containing proteins. Importantly, we define a specific consensus binding mode for the recognition of GlcNAc oligomers by single LysM domains.


Use of chemical mutagenesis in mouse embryonic stem cells.
The chemical mutagenesis of mouse embryonic stem (ES) cells is an approach complementary to chemical mutagenesis of spermatogonia in whole animals. It has great potential to contribute significantly to the generation of a comprehensive collection of multiple alleles for most mammalian genes and to facilitate the progression from gene sequence to gene functional analyses. The general strategy includes the treatment of ES cells with a chemical mutagen and the isolation of individual mutagenized clones that are then cultured in duplicate. Whereas one set of samples is cryopreserved for archiving and subsequent generation of germline chimeras by means of blastocyst injection, the second set is used for genotype- or phenotype-driven screens to identify mutant alleles.


An epidemiological survey of lacrimal fossa lesions in Japan: number of patients and their sex ratio by pathological diagnosis.
To report the results of a survey conducted on lacrimal fossa lesions in Japan. The subjects were patients with lacrimal fossa lesions pathologically diagnosed between January 1995 and December 1997. We sent survey questionnaires to 1201 hospitals with training facilities accredited by the Japanese Ophthalmological Society and determined the number of patients and their sex ratio by pathological diagnosis. Based on returned questionnaires, 311 cases were enrolled in the survey. Among tumors with high frequency, there were 86 cases of pleomorphic adenoma and 19 cases of adenoid cystic carcinoma in the category of epithelial tumor; 55 cases of malignant lymphoma and 32 cases of reactive lymphoid hyperplasia in the category of nonepithelial tumor; and 50 cases of inflammation and 22 cases of cystic lesion in the category of nonneoplastic lesion. The patient ages ranged from 3 months to 89 years, with the median age 52 years and 2 months. The sex ratio by pathological diagnosis revealed that women had a higher rate than men of pleomorphic adenoma, whereas men had a higher rate than women of malignant epithelial tumor.


Serum-free medium for growth factor-dependent and -independent plasmacytomas and hybridomas.
A serum-free medium was developed for culture of plasmacytomas and hybridomas that are dependent upon or independent of the presence of specific P388D1-derived polypeptide growth factors. Possibly due to the stringency of requirements for culturing such plasmacytomas, a highly advantageous combination of components was developed. The medium, SFM, contains RPMI 1640, beta-mercaptoethanol, Hepes buffer, reduced glutathione (GSH), selenite (Se), pyruvate, transferrin, albumin, soybean lipids, and low density lipoproteins. A cooperative effect of GSH and Se is observed. SFM supports the continuous, prodigious growth of every B cell line tested, including a variety of the plasmacytomas, hybridomas, myeloma fusion partners and lymphoma cell lines, as well as the macrophage-like cell line P388D1. All of the B cell lines grow equally as well in SFM as in serum-containing medium. Hybridoma lines from mouse-mouse and rat-mouse fusions continue to produce monoclonal antibodies which can then be purified in a single-step procedure. The cells can be cloned out and frozen down in SFM. In addition, the medium is highly effective for establishment of plasmacytoma cell lines from some transplantable plasmacytomas, including early generation tumors.


Structural and functional studies of trans-encoded HLA-DQ2.3 (DQA1*03:01/DQB1*02:01) protein molecule.
MHC class II molecules are composed of one α-chain and one β-chain whose membrane distal interface forms the peptide binding groove. Most of the existing knowledge on MHC class II molecules comes from the cis-encoded variants where the α- and β-chain are encoded on the same chromosome. However, trans-encoded class II MHC molecules, where the α- and β-chain are encoded on opposite chromosomes, can also be expressed. We have studied the trans-encoded class II HLA molecule DQ2.3 (DQA1*03:01/DQB1*02:01) that has received particular attention as it may explain the increased risk of certain individuals to type 1 diabetes. We report the x-ray crystal structure of this HLA molecule complexed with a gluten epitope at 3.05 Å resolution. The gluten epitope, which is the only known HLA-DQ2.3-restricted epitope, is preferentially recognized in the context of the DQ2.3 molecule by T-cell clones of a DQ8/DQ2.5 heterozygous celiac disease patient. This preferential recognition can be explained by improved HLA binding as the epitope combines the peptide-binding motif of DQ2.5 (negative charge at P4) and DQ8 (negative charge at P1). The analysis of the structure of DQ2.3 together with all other available DQ crystal structures and sequences led us to categorize DQA1 and DQB1 genes into two groups where any α-chain and β-chain belonging to the same group are expected to form a stable heterodimer.


Providing better asthma care for children in school.
Assessing the needs of children, young people and families is a fundamental part of the school nurse's role. This article describes a project in Doncaster that has enabled a partnership working with children, young people, families, school nurses and school staff aimed at providing improved services throughout the primary and secondary school day.


Quantitative processed images acquired by histogram-SNR imaging used to evaluate parenchymal heterogeneity in the liver.
To evaluate a new system for displaying processed images of liver parenchyma based on quantitative estimation of heterogeneity by texture analysis. We measured the signal to noise ratio, one of the first-order statistics in the histogram of enveloped amplitude of radio-frequency backscattered echoes, using a 3.75-MHz transducer with texture analysis in conjunction with a new method in which the small ROI (region of interest) is segmented into multiple layers to minimize the influence of tissue attenuation and beam diffraction. In our computerized system, gray-display and color-display images, two types of processed images, were produced from the visual intensity of each small ROI, which was based on its signal to noise ratio. We studied 10 cases of normal liver, 10 cases of fatty liver, and 10 cases of cirrhotic liver. The processed images obtained from these livers were reviewed to observe their features and to compare their usefulness in estimating the heterogeneity of the liver parenchyma with that of conventional B-mode images. Gray-display images of cirrhotic livers appeared much blacker than the images produced from other disorders, and color-display images of cirrhotic liver appeared much bluer or greener than the others. Rate of correct diagnosis from B-mode images was 68.3 ±6.8%; from gray-display images, 85.8±7.4%; and from color-display images, 91.7±8.2%. Rate of correct assessment from B-mode images and gray-display images was significantly correlated (p=0.0015), as was rate of correct assessment from the B-mode images and the color-display images (p=0.0060). The processed images obtained using this computerized system contributed to the correct and objective interpretation of the heterogeneity of the liver parenchyma.


Arginine site 264 in murine estrogen receptor-α is dispensable for the regulation of the skeleton.
Mutation of arginine 264 in ERα has been shown to abrogate rapid membrane ERα-mediated endothelial effects. Our novel finding that mutation of R264 is dispensable for ERα-mediated skeletal effects supports the concept that R264 determines tissue specificity of ERα. Estrogen protects against bone loss but is not a suitable treatment due to adverse effects in other tissues. Therefore, increased knowledge regarding estrogen signaling in estrogen-responsive tissues is warranted to aid the development of bone-specific estrogen treatments. Estrogen receptor-α (ERα), the main mediator of estrogenic effects in bone, is widely subjected to posttranslational modifications (PTMs). In vitro studies have shown that methylation at site R260 in the human ERα affects receptor localization and intracellular signaling. The corresponding amino acid R264 in murine ERα has been shown to have a functional role in endothelium in vivo, although the methylation of R264 in the murine gene is yet to be empirically demonstrated. The aim of this study was to investigate whether R264 in ERα is involved in the regulation of the skeleton in vivo. Dual-energy X-ray absorptiometry (DEXA) analysis at 3, 6, 9, and 12 mo of age showed no differences in total body areal bone mineral density (BMD) between R264A and wild type (WT) in either female or male mice. Furthermore, analyses using computed tomography (CT) demonstrated that trabecular bone mass in tibia and vertebra and cortical thickness in tibia were similar between R264A and WT mice. In addition, R264A females displayed a normal estrogen treatment response in trabecular bone mass as well as in cortical thickness. Furthermore, uterus, thymus, and adipose tissue responded similarly in R264A and WT female mice after estrogen treatment. In conclusion, our novel finding that mutation of R264 in ERα does not affect the regulation of the skeleton, together with the known role of R264 for ERα-mediated endothelial effects, supports the concept that R264 determines tissue specificity of ERα.NEW & NOTEWORTHY Mutation of arginine 264 in ERα has been shown to abrogate rapid membrane ERα-mediated endothelial effects. Our novel finding that mutation of R264 is dispensable for ERα-mediated skeletal effects supports the concept that R264 determines tissue specificity of ERα.


Does high sensitive CRP improve cardiovascular risk prediction in metabolic syndrome among the aged?
To analyze whether an elevated level of high hsCRP has an additive effect on metabolic syndrome (MetS) in predicting future cardiovascular events (CVEs) as well as on all-cause mortality among the aged subjects. A prospective, population-based study with a 9-year follow-up. The study population consisted of persons aged 64 and above in 1998-99 without vascular disease and CRP less than 10 mg/l at baseline (n = 733). Adjusted hazard ratios (HRs) and their 95% confidence intervals (CIs) for CVEs and all-cause mortality predicted by baseline MetS (defined by both International Diabetes Federation (IDF) and World Health Organization (WHO)) and hsCRP-level were estimated. During the 9-year follow-up, a total of 142 CVEs and 206 deaths occurred. After multivariable adjustment, no significant interactions were found between hsCRP and MetS in CVEs (IDF: p = 0.828; WHO: p = 0.572) or in all-cause mortality (IDF: p = 0.113; WHO: p = 0.374). HsCRP was not associated with the occurrence of CVEs (IDF: HR = 1.10, 95% CI = 0.92-1.32, p = 0.281; WHO: HR = 1.10, 95% CI = 0.93-1.32, p = 0.247) or with all-cause mortality (IDF: HR = 1.12, 95% CI = 0.97-1.29, p = 0.134; WHO: HR = 1.11, 95% CI = 0.96-1.28, p = 0.146). It seems that hsCRP does not give any extra value in evaluation of CVE risk or all-cause mortality of older subjects with MetS.


Complications of Dentoalveolar Surgery.
This article explores how to prevent and manage complications of dentoalveolar surgery. Many complications are avoidable. Surgical skills and knowledge of anatomy play an important role in prevention of complications. Prevention starts with detailed history and physical examination of the patient. Key to perioperative management of patients is risk assessment. Without a proper history and physical examination, the clinician is unable to assess the risk of performing surgery and anesthesia for each patient. Some illnesses and medications increase the risk of complications. The following complications are discussed: alveolar osteitis, displacement, fracture, hemorrhage, infection, nonhealing wound, oroantral communication, swelling, and trismus.


Melanosis of the cervix.
Benign and malignant melanotic cervical lesions are rare and require biopsy to rule out melanoma. Reported is a case of cervical melanosis, defined as benign epithelial pigmentation.


Motor symptoms in genetic frontotemporal dementia: developing a new module for clinical rating scales.
To investigate the optimal method of adding motor features to a clinical rating scale for frontotemporal dementia (FTD). Eight hundred and thirty-two participants from the international multicentre Genetic FTD Initiative (GENFI) study were recruited: 522 mutation carriers (with C9orf72, GRN and MAPT mutations) and 310 mutation-negative controls. A standardised clinical questionnaire was used to assess eight motor symptoms (dysarthria, dysphagia, tremor, slowness, weakness, gait disorder, falls and functional difficulties using hands). Frequency and severity of each motor symptom was assessed, and a principal component analysis (PCA) was performed to identify how the different motor symptoms loaded together. Finally, addition of a motor component to the CDR® plus NACC FTLD was investigated (CDR® plus NACC FTLD-M). 24.3% of mutation carriers had motor symptoms (31.7% C9orf72, 18.8% GRN, 19.3% MAPT) compared to 6.8% of controls. Slowness and gait disorder were the commonest in all genetic groups while tremor and falls were the least frequent. Symptom severity scores were similar to equivalent physical motor examination scores. PCA revealed that all motor symptoms loaded together so a single additional motor component was added to the CDR® plus NACC FTLD to form the CDR® plus NACC FTLD-M. Individual global scores were more severe with the CDR® plus NACC FTLD-M, and no patients with a clinically diagnosed motor disorder (ALS/FTD-ALS or parkinsonism) were classified anymore as asymptomatic (unlike the CDR® plus NACC FTLD alone). Motor features are present in mutation carriers at all disease stages across all three genetic groups. Inclusion of motor symptoms in a rating scale that can be used in future clinical trials will not only ensure a more accurate severity measure is recorded but that a wider spectrum of FTD phenotypes can be included in the same trial.


Tryptophan consumption and indoleamines production by peritoneal cavity macrophages.
Melatonin has been shown to regulate several immune functions, and some authors showed that leukocytes are also able to produce the indolamine. In fact, it seems to take part in some immunoregulatory axis, including that related to interferon (IFN) production. So, we evaluated the rate of tryptophan consumption and melatonin and serotonin production in peritoneal cavity-isolated macrophages and the effect of IFN-alpha and -gamma, lipopolysaccharide (LPS), and phorbol myristate acetate (PMA) on such parameters. Our results indicate that macrophages obtained from the peritoneal cavity of normal rats when incubated with tryptophan show an increase in arylalkylamine N-acetyltransferase activity that corresponds to an increased melatonin production, as determined in the incubation medium. This process is regulated by IFN-alpha and -gamma, PMA, LPS, and the serum from tumor-bearing rats, opening the possibility of speculation about different immunoregulatory loops acting through the balance of melatonin/serotonin production by such cells.


Interaction of the B subunit of cholera toxin with endogenous ganglioside GM1 causes changes in membrane potential of rat thymocytes.
The fluorescent anionic dye, bisoxonol, and flow cytometry have been used to monitor changes in the membrane potential of rat thymocytes exposed to the B subunit of cholera toxin. The B subunit induced a rapid hyperpolarization, which was due to activation of a Ca2+-sensitive K+ channel. Reduction of extracellular Ca2+ to less than 1 microM by the addition of [ethylene-bis(oxyethylenenitrilo)]tetraacetic acid immediately abolished the hyperpolarization caused by the B subunit. Cells treated with quinine and tetraethylammonium lost their ability to respond to the B subunit, whereas 4-aminopyridine did not have any effect. Thus, calcium-sensitive and not voltage-gated K+ channels appeared to be responsible for the hyperpolarization. The results of ion substitution experiments indicated that extracellular Na+ was not essential for changes in membrane potential. Further studies with ouabain, amiloride and furosemide demonstrated that electrogenic Na+/K+ ATPase, Na+/H+ antiporter and Na+/K+/Cl- cotransporter, respectively, were not involved in the hyperpolarization process induced by the B subunit. Thus, crosslinking of several molecules of ganglioside GM1 on the cell surface of rat thymocytes by the pentavalent B subunit of cholera toxin modulated plasma membrane permeability to K+ by triggering the opening of Ca2+-sensitive K+ channels. A role for gangliosides in regulating ion permeability would have important implications for the function of gangliosides in various cellular phenomena.


Regulation of glucose-6-phosphate dehydrogenase in spinach chloroplasts by ribulose 1,5-diphosphate and NADPH/NADP+ ratios.
The activity of glucose-6-phosphate dehydrogenase (EC 22.214.171.124) FROM SPINACH CHLOROPLASTS IS STRONGLY REGULATED BY THE RATIO OF NADPH/NADP+, with the extent of this regulation controlled by the concentration of ribulose 1,5-diphosphate. Other metabolites of the reductive pentose phosphate cycle are far less effective in mediating the regulation of the enzyme activity by NADPH/NADP+ ratio. With a ratio of NADPH/NADP+ of 2, and a concentration of ribulose 1,5-diphosphate of 0.6 mM, the activity of the enzyme is completely inhibited. This level of ribulose 1,5-diphosphate is well within the concentration range which has been reported for unicellular green algae photosynthesizing in vivo. Ratios of NADPH/NADP+ of 2.0 have been measured for isolated spinach chloroplasts in the light and under physiological conditions. Since ribulose 1,5-diphosphate is a metabolite unique to the reductive pentose phosphate cycle and inhibits glucose-6-phosphate dehydrogenase in the presence of NADPH/NADP+ ratios found in chloroplasts in the light, it is proposed that regulation of the oxidative pentose phosphate cycle is accomplished in vivo by the levels of ribulose 1,5-diphosphate, NADPH, and NADP+. It already has been shown that several key reactions of the reductive pentose phosphate cycle in chloroplasts are regulated by levels of NADPH/NADP+ or other electron-carrying cofactors, and at least one key-regulated step, the carboxylation reaction is strongly affected by 6-phosphogluconate, the metabolic unique to the oxidative pentose phosphate cycle. Thus there is an interesting inverse regulation system in chloroplasts, in which reduced/oxidized coenzymes provide a general regulatory mechanism. The reductive cycle is activated at high NADPH/NADP+ ratios where the oxidative cycle is inhibited, and ribulose 1,5-diphosphate and 6-phosphogluconate provide further control of the cycles, each regulating the cycle in which it is not a metabolite.


High-risk antenatal women's perceptions of dietitian appointments and information.
The dietitian service at a metropolitan health service in Queensland, Australia has a non-engagement rate for high-risk antenatal women of 50%. Determine which attributes are related to non-attendance at dietitian appointments, and women's perceptions and attitudes towards dietitian appointments during pregnancy. An explanatory mixed-methods design was utilised, with first phase including 103 antenatal women referred to a dietitian in 2021 and compared the attributes of those who attended with those who did not engage. Queensland Health electronic databases were used to collect attribute data, which were then analysed with Jamovi (version 1.6) for descriptive, correlational, multivariate analyses of variance MANOVA. Second phase included seven semi-structured interviews with women attending a dietitian appointment, and subsequently analysed through thematic analysis. Distance from clinic was not related to clinic attendance, and women reported they would attend regardless of distance or work status. Non-attendance was related to higher gravidity, parity, and if referred for obesity, but not previous gastric sleeve or underweight referral. Six themes were identified from the interview data: "Women want to be treated like an individual," "It's all about expectations," "Midwives hold the key," "Preferences in receiving dietary information," "Weight has been a long-term problem and is a sensitive topic," and "Barriers to attendance." Antenatal services can adjust service delivery to improve engagement in weight management services during pregnancy. Telehealth appointments may reduce non-engagement due to distance from clinic. Demystifying the dietitian appointment, ensuring non-judgemental referral processes and collaboration between midwives and dietitians will ensure that women value the service.


Flow kinetics of nylon open-tubular and beaded immobilized glucose oxidase reactors.
Equations describing the flow kinetics of immobilized glucose oxidase in open nylon tubes and in tubes filled with solid glass spheres were experimentally determined. Reactors of three different tube (dt) and bead (db) diameters were tested using various linear flow rates (vf) and glucose concentrations ([S]). The kinetics of the open-tubular reactors were described by [P] = 1.5.10(-3) [S] L0.86 vf-0.78 dt-0.9 and the kinetics of the beaded-tubular reactors by [P] = 5.10(-3) [S] L0.98 vf-0.75 dt-1.0 (db/dt)2.7, where [P] equals the concentration of H2O2 formed. The aspect ratio, db/dt, is the critical design factor for beaded reactors.


Superficial migratory thrombophlebitis and factor XII deficiency.
A patient with painful migratory erythematous nodules for 7 years is presented. The nodules, which were localized on the lower and upper extremities, progressed to palpable cords. Multiple venograms showed no evidence of deep vein thrombosis. Skin biopsy specimens were diagnostic of superficial thrombophlebitis. There was no evidence of internal malignancy. Extensive evaluation for an underlying hypercoagulable state was remarkable for a factor XII level 17% of normal. The patient was unresponsive to a wide range of treatments. The recalcitrant nature of his disease and lack of deep venous involvement are unique. An underlying hypercoagulable state should be considered when the diagnosis of superficial migratory thrombophlebitis is considered.


Neurometabolic characteristics in the anterior cingulate gyrus of Alzheimer's disease patients with depression: a (1)H magnetic resonance spectroscopy study.
Depression is a common comorbid psychiatric symptom in patients with Alzheimer's disease (AD), and the prevalence of depression is higher among people with AD compared with healthy older adults. Comorbid depression in AD may increase the risk of cognitive decline, impair patients' function, and reduce their quality of life. However, the mechanisms of depression in AD remain unclear. Here, our aim was to identify neurometabolic characteristics in the brain that are associated with depression in patients with mild AD. Thirty-seven patients were evaluated using the Neuropsychiatric Inventory (NPI) and Hamilton Depression Rating Scale (HAMD-17), and divided into two groups: 17 AD patients with depression (D-AD) and 20 non-depressed AD patients (nD-AD). Using proton magnetic resonance spectroscopy, we characterized neurometabolites in the anterior cingulate gyrus (ACG) of D-AD and nD-AD patients. Compared with nD-AD patients, D-AD patients showed lower N-acetylaspartate/creatine (NAA/Cr) and higher myo-inositol/creatine (mI/Cr) in the left ACG. NPI score correlated with NAA/Cr and mI/Cr in the left ACG, while HAMD correlated with NAA/Cr. Our findings show neurometabolic alterations in D-AD patients. Thus, D-AD pathogenesis may be attributed to abnormal activity of neurons and glial cells in the left ACG.


The potential of lipid- and polymer-based drug delivery carriers for eradicating biofilm consortia on device-related nosocomial infections.
Microbial biofilms are microcosm attaching irreversibly to abiotic or biotic surfaces and they are promulgated as congregate of single or multiple populations. The potential of lipid- and polymer-based drug delivery carriers for eradicating biofilm consortia on device-related nosocomial infections is explored in this review. Liposomes-loaded with antimicrobial agents could effectively be applied as anti-biofilm coating to reduce microbial adhesion/colonisation onto medical devices and as drug delivery carriers to biofilm interfaces and in intracellular infection. Many polymer-based carrier systems have also been proposed, including those based on biodegradable polymers such as poly(lactide co-glycolide) as well as fibrous scaffolds and thermoreversible hydrogels and surface (properties) modified polymeric catheter materials such as antimicrobial, antiseptic or metallic substances-coated polymeric materials. Their contribution to the prevention/resolution of infection is reviewed.


A new member of a secretory protein gene family in the dipteran Chironomus tentans has a variant repeat structure.
We describe the structure of a gene expressed in the salivary gland cells of the dipteran Chironomus tentans and show that it encodes 1 of the approximately 15 secretory proteins exported by the gland cells. This sp115,140 gene consists of approximately 65 copies of a 42-bp sequence in a central uninterrupted core block, surrounded by short nonrepetitive regions. The repeats within the gene are highly similar to each other, but divergent repeats are present in a pattern which suggests that the repeat structure has been remodeled during evolution. The 42-bp repeat in the gene is a simple variant of the more complex repeat unit present in the Balbiani ring genes, encoding four of the other secretory proteins. The structure of the sp115,140 gene suggests that related repeat structures have evolved from a common origin and resulted in the set of genes whose secretory proteins interact in the assembly of the secreted protein fibers.


Sound-induced brain activity depends on stimulus subjective salience in female zebra finches.
A key point in the study of acoustic perception is whether brain responsiveness to sounds depends on sound acoustic structure or sound perceptive salience. Songbirds provide some evidence that higher auditory regions are sensitive to the subjective importance of the stimulus for the subject. In the present paper, we compare brain activation elicited by mate versus non-mate calls in female zebra finches Taeniopygia guttata. Using playback, we examined the responsiveness of the caudal telencephalon by measuring the evoked expression of the immediate early gene ZENK. Our results show that mate calls elicit a significantly higher ZENK expression than the calls of another male in hippocampus, but not in auditory areas. Using a hierarchical ascending classification, we show that this difference in brain activation is not explained by call acoustic structure, but relies on call identity. Thus, these results give evidence for a genomic response to calls in hippocampus that differentiate between call identity, and not between call structure. Our study gives further insight into the implication of the hippocampus in sound recognition in female songbirds.


Long-term follow-up results of transsphenoidal surgery for Cushing's disease in a single centre using strict criteria for remission.
Transsphenoidal selective adenomectomy (TSA) is widely accepted as the treatment of choice for Cushing's disease but not all patients are cured by this procedure. The success of surgery depends on the skill and experience of the surgeon but the criteria used to define remission are highly variable. We have analysed the outcome following surgery in our centre using the stringent requirement of a postoperative serum cortisol of < 50 nmol/l as our definition of remission and assessed whether changes in surgical policy, including a greater emphasis on selective procedures and the move in recent years to a single surgeon undertaking all pituitary surgery, have improved complication and remission rates. The case notes, histology and pituitary imaging of 54 consecutive patients (42 females, mean age 41 years) with pituitary-dependent Cushing's syndrome who had undergone transsphenoidal surgery between January 1980 and November 2000 were reviewed. Follow-up was for a median of 6 years (range 6 months to 21 years). One patient died within 1 week of surgery (1.9%) and major morbidity occurred in eight patients (15%). Clinical and biochemical remission was achieved in 41 patients (77%) with only two recurrences (5%) to date. Success was related to tumour size with 37 (86%) of 43 intrasellar lesions successfully resected compared with only four (40%) of 10 extrasellar adenomas. Twenty-four (59%) of those in remission developed partial or complete hypopituitarism compared with four (33%) of those not in remission. The extent of surgical exploration predicted the development of hypopituitarism (88% total hypophysectomy, 33% hemihypophysectomy, 14% selective adenomectomy) but not remission (75% total hypophysectomy, 87% hemihypophysectomy, 71% selective adenomectomy). Among complications, an excess of venous thromboembolic disease was noted, with three patients (6%) developing deep venous thrombosis or pulmonary embolism postoperatively. Comparison of the data for individual surgeons revealed an improvement in outcome over time, with 100% remission of microadenomas, 29% hypopituitarism and 12% complications following the move to a single surgeon undertaking all pituitary surgery. Transsphenoidal surgery is a safe and effective treatment for Cushing's disease and our results compare favourably with those from published series, the majority of which comprise relatively small numbers. The presence of an intrasellar lesion and postoperative serum cortisol < 50 nmol/l are good predictors of remission in the long term but historically in our centre this can only be achieved in a significant number of patients at the expense of some degree of hypopituitarism. However, the surgical outcome for Cushing's disease, including a reduced frequency of hypopituitarism, can be improved if patients are operated on by a single pituitary surgeon, using selective adenomectomy as the preferred surgical approach wherever possible.


BIS does not predict dreams reported after anaesthesia.
In earlier studies, between 1% and 57% of patients have been reported to dream during anaesthesia. Thus, dreaming is much more common than definite memories of real events. We wanted to examine whether dreaming during anaesthesia is related to insufficient hypnotic action, as indicated by BIS levels and, thus, may constitute a risk for awareness. After IRB approval, 2653 consecutive surgical patients were included. BIS registrations were recorded continuously during the anaesthetic procedure. The patients were interviewed on three occasions after anaesthesia. Standard questions, according to Brice, to evaluate awareness and dreaming during anaesthesia were asked. The dreams were categorized as either pleasant/neutral or unpleasant without any further evaluation of the dream content. Episodes with a mean BIS below 40, above 60 and above 70 were identified and subdivided according to duration (1, 2, 4 and 6 min, respectively). The total time as well as number and duration of episodes for the three BIS-levels were used to analyze any relation to reported dreaming. The mean BIS was also analyzed. Dreaming during anaesthesia was reported by 211 of patients (8.0%) on at least one of the post-operative interviews. BIS data did not show any significant correlation with dreaming, and neither did any of the tested case-specific parameters (gender, age, ASA group, BMI, use of relaxants, induction agent, maintenance agent, length of procedure, omitting N(2)O and concomitant regional anaesthesia). Dreaming during anaesthesia seems to be a separate phenomenon, not in general related to insufficient anaesthesia as indicated by high BIS levels.


Characterization of three new HLA-A*11 alleles in Russian individuals by next-generation sequencing.
Three new HLA-A*11:12:02, A*11:01:104 and A*11:355:02 alleles detected in Russian individuals.


Patient-specific and gene-corrected induced pluripotent stem cell-derived endothelial cells elucidate single-cell phenotype of pulmonary veno-occlusive disease.
Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension characterized by the preferential remodeling of the pulmonary venules. Hereditary PVOD is caused by biallelic variants of the EIF2AK4 gene. Three PVOD patients who carried the compound heterozygous variants of EIF2AK4 and two healthy controls were recruited and induced pluripotent stem cells (iPSCs) were generated from human peripheral blood mononuclear cells (PBMCs). The EIF2AK4 c.2965C>T variant (PVOD#1), c.3460A>T variant (PVOD#2), and c.4832_4833insAAAG variant (PVOD#3) were corrected by CRISPR-Cas9 in PVOD-iPSCs to generate isogenic controls and gene-corrected-iPSCs (GC-iPSCs). PVOD-iPSC-endothelial cells (ECs) exhibited a decrease in GCN2 protein and mRNA expression when compared with control and GC-ECs. PVOD-ECs exhibited an abnormal EC phenotype featured by excessive proliferation and angiogenesis. The abnormal phenotype of PVOD-ECs was normalized by protein kinase B inhibitors AZD5363 and MK2206. These findings help elucidate the underlying molecular mechanism of PVOD in humans and to identify promising therapeutic drugs for treating the disease.


Outcome after a dose "de-intensification" strategy with anti-TNF drugs in patients with Crohn's disease.
Dose "intensification" is a recommended strategy to recover therapeutic benefit in Crohn's disease (CD) patients who have lost initial response to anti-TNF therapy. Once patients have achieved remission, dose "de-intensification" can be used for cost and safety reasons. The primary aim of this study was to evaluate the long-term durability of remission after stepping down anti-TNF therapy. The secondary aim was to identify predictive factors associated with loss of response after "de-intensification" and to evaluate the effectiveness of a second "re-intensification" in patients who lost response after the treatment was stepped down. We evaluated CD patients who received at least one standard anti-TNF dosage after achieving remission with "intensified" anti-TNF therapy. Twenty-four patients were included. The treatment was "intensified" because of partial response in 11 patients, loss of response in 10, and primary lack of response in 3. Eight of the 24 patients had lost response after a median follow-up of only 7 months after "de-intensification" of the anti-TNF therapy. The anti-TNF drug was "intensified" again in all 8 patients. Three patients did not respond to the new "intensification", two had partial response and three achieved remission. On univariate analysis, no predictive factors were identified for loss of response after treatment "de-intensification". After only 7 months of follow-up, one-third of the CD patients who received "de-intensification" therapy lost response; of these, two-thirds did not achieve response after subsequent "re-intensification".


Progressive enhancement of alpha activity and visual function in patients with optic neuropathy: a two-week repeated session alternating current stimulation study.
Repetitive transorbital alternating current stimulation (rtACS) can improve visual deficits in patients with optic nerve damage. Recent retrospective results suggest that rtACS enhances oscillatory brain activity. The exact mechanisms of rtACS are unclear and little is known about possibly frequency-specific neural-plastic mechanisms. An association between bandwidth-confined neural-entrainment and vision recovery maximization could offer a novel therapeutic option for patients with optic neuropathy. The goal of this prospective open-label study was to investigate if the enhancement of rhythmic brain activity over 10 days of consecutive rtACS stimulation is associated with visual field recovery. The secondary goal was to investigate neurophysiological mechanisms related to frequency dependent adaptive plasticity. 18 Patients with visual field impairments resulting from pre-chiasmatic partial optic nerve damage received rtACS on 10 consecutive days. Daily, subject-specific treatment parameters (<500 μA, 9-37 Hz, 25-40 min/day) were defined and EEG-spectra collected prior to and after rtACS. Visual field data was collected at day 1 and 10. The change of spectral-power in classic bandwidths were investigated and correlated with visual field deficit recovery. After 10 days of rtACS alpha-power over bilateral occipital electrodes was significantly larger than at baseline (F(Time x alpha-power)p < 0.01). This effect was progressive over subsequent days of stimulation (cubic-fit, R(2) 0.70, RMSE 0.008). Perimetric results improved significantly, but they were not associated with changes in alpha-synchronization. rtACS can induce cumulative bandwidth-confined changes in brain rhythms over multiple sessions. These findings are in line with the notion of brain-state dependent [1] and bandwidth-confined entrainment [2] as well as rtACS facilitated visual recovery [3].


Er-xian decoction drug-containing serum promotes Mc3t3-e1 cell proliferation and osteogenic differentiation via regulating BK channel.
Er-xian Decoction (EXD) is a well-known prescription widely used to prevent and treat climacteric syndrome and osteoporosis in China. BK channel positively affects osteoblast bone formation in vitro. However, it is still unclear whether the effect of EXD on promoting osteoblasts osteogenic differentiation is related to BK channel. The study is aimed at determining whether the EXD-containing serum promotes the proliferation of osteoblasts and their differentiation through BK channel. The chemical compounds of EXD were analyzed by UPLC-Q-TOF/MS. An osteogenic induction medium (OM) was used to induce MC3T3-E1 cells' osteogenic differentiation. The effects of EXD-containing serum and tetraethylammonium (TEA) on the proliferation activity of Mc3t3-e1 cells were detected by CCK-8 assay. ALP activity was determined by an alkaline phosphatase kit. The protein expression (BMP2, OPG, and COL1) was analyzed by Western blot, and the mRNA expression (Runx2, OPG, and BMP2) was assessed by real-time PCR. Alizarin red was used to stain the mineralized region of osteoblasts. In addition, we analyzed the relationship between BK channel and its downstream PTEN/Akt/Foxo1 signaling pathway. 72 compounds were identified by UPLC-Q-TOF/MS analysis in EXD. Mangiferin, ferulic acid, berberine, and icariin were main active components of EXD. EXD-containing serum could enhance the cell viability of MC3T3-E1 cells by decreasing the expression of BKα protein. EXD-containing serum increased ALP activity and calcium nodule formation of Mc3t3-e1 cells, promoted the protein expression of BKα, COL1, BMP2, OPG, and the mRNA expression of RUNX2, OPG, and BMP2, however, these effects can be reversed after adding TEA. In addition, EXD-containing serum could upregulate phosphorylation of Akt and Foxo1 in osteogenic-induced Mc3t3-e1 cells, and lower the expression of PTEN. And these effects of EXD-containing serum could be reduced by TEA. The effect of EXD-containing serum on promoting cell proliferation and osteogenic differentiation of Mc3t3-e1 cells might be linked to the regulation of BK channel.


Effective treatment of olive mill effluents from two-phase and three-phase extraction processes by batch membranes in series operation upon threshold conditions.
Production of olive oil results in the generation of high amounts of heavy polluted effluents characterized by extremely variable contaminants degree, leading to sensible complexity in treatment. In this work, batch membrane processes in series comprising ultrafiltration (UF), nanofiltration (NF) and reverse osmosis (RO) are used to purify the effluents exiting both the two-phase and tree-phase extraction processes to a grade compatible to the discharge in municipal sewer systems in Spain and Italy. However, one main problem in applying this technology to wastewater management issues is given by membrane fouling. In the last years, the threshold flux theory was introduced as a key tool to understand fouling problems, and threshold flux measurement can give valuable information regarding optimal membrane process design and operation. In the present manuscript, mathematical approach of threshold flux conditions for membranes operation is addressed, also implementing proper pretreatment processes such as pH-T flocculation and UV/TiO2 photocatalysis with ferromagnetic-core nanoparticles in order to reduce membranes fouling. Both influence the organic matter content as well as the particle size distribution of the solutes surviving in the wastewater stream, leading, when properly applied, to reduced fouling, higher rejection and recovery values, thus enhancing the economic feasibility of the process.


The role of the third acid-fast bacillus smear in tuberculosis screening for infection control purposes: A controversial topic revisited.
Recent studies have suggested that two negative acid-fast bacillus (AFB) smears may be as effective as three when screening patients with suspected Mycobacterium tuberculosis for respiratory isolation purposes. However, current recommendations in Canada, the United States and Europe still support a three-smear approach. The microbiology database of a tertiary care hospital was searched for sputum, tracheal aspirates and bronchoalveolar lavage samples from 2003 to 2007 that had been sent for mycobacterial testing. The first patient specimen to become AFB smear positive was noted. As well, the time required to collect the third specimen in hospitalized patients who remained smear negative was used to estimate the savings in isolation costs associated with a two-smear approach. There were 8347 respiratory specimens from 5168 patients in the five-year period. Of these patients, 2.2% (116 of 5168) were AFB smear positive, of whom 55.2% (64 of 116) were culture positive for Mycobacterium tuberculosis. Overall 89% (57 of 64) of patients were identified as being AFB smear positive by the first smear, 7.8% (five of 64) were identified by the second smear and 3.2% (two of 64) were identified by further smears. Smear-negative patients spent a combined 710 days in isolation awaiting collection of the third sample at a cost of approximately $142,000 over five years. A two-smear approach for discontinuation of respiratory isolation precautions is safe and has the potential to reduce hospital expenditures.


Biochemical characterization of xylanase GH11 isolated from Aspergillus niger BCC14405 (XylB) and its application in xylooligosaccharide production.
To develop an endo-β-1,4-xylanase with high specificity for production of prebiotic xylooligosaccharides that optimally works at moderate temperature desirable to reduce the energy cost in the production process. The xylB gene, encoding for a glycosyl hydrolase family 11 xylanase from a thermoresistant fungus, Aspergillus niger BCC14405 was expressed in a methylotrophic yeast P. pastoris KM71 in a secreted form. The recombinant XylB showed a high specific activity of 3852 and 169 U mg-1 protein on beechwood xylan and arabinoxylan, respectively with no detectable side activities against different forms of cellulose (Avicel Ò PH101 microcrystalline cellulose, phosphoric acid swollen cellulose and carboxymethylcellulose). The enzyme worked optimally at 45 °C, pH 6.0. It showed a specific cleavage pattern by releasing xylobiose (X2) as the major product from xylooligosaccharides (X3 to X6) substrates. The highest XOS yield of 708 mg g-1 substrate comprising X2, X3 and X6 was obtained from beechwood xylan hydrolysis. The enzyme is potent for XOS production and for saccharification of lignocellulosic biomass.


Immunohistochemical analysis of the role and relationship between Notch-1 and Oct-4 expression in urinary bladder carcinoma.
Most tumors contain a minor population of cancer stem cells that are responsible for tumor heterogeneity, resistance to therapy and recurrence. Oct-4 is a transcription factor responsible for self-renewal of stem cells, whereas the Notch family of receptors and ligands may play a pivotal role in the regulation of stem cell maintenance and differentiation. This study aimed at an evaluation of Oct-4 and Notch-1 expression in both carcinoma and stromal cells of 83 cases of primary bladder carcinoma and to study the relationship between them. Notch-1 was expressed in carcinoma and stromal cells of all malignant cases, where expression in both cell types was correlated with parameters indicating differentiation, such as low grade (p < 0.05) and less proliferation (p < 0.05). However, Notch-1 expression in stromal cells was associated with nodal metastasis (p = 0.016) and advanced stage (p = 0.030). 56.6 and 75.9% of carcinoma and stromal cells of malignant cases showed Oct-4 expression, respectively. Oct-4 expression in carcinoma cells or stromal cells was associated with aggressive features of bladder carcinoma, such as poor differentiation (p = 0.001), high proliferation (p < 0.001, 0.030), and liability for recurrence (p = 0.010, p < 0.001). There was an inverse relationship between Notch-1 and Oct-4 expression in carcinoma cells (p = 0.002), but stromal expression of Notch-1 was found to be associated with a nuclear pattern of Oct-4 expression in carcinoma cells (p = 0.030). Oct-4 as a stem cell marker is expressed in carcinoma cells and in stromal cells of bladder carcinoma, where they may cooperate in the progression of bladder carcinoma by acquiring aggressive features, such as a liability for recurrence and dissemination. Notch-1 is also expressed in both carcinoma cells and stromal cells of bladder carcinoma. Although they could share in enhancing differentiation, stromal expression of Notch-1 may have a bad impact, possibly through up-regulation of the active nuclear form of Oct-4 in carcinoma cells.


Inhibition of gravitropism in oat coleoptiles by the calcium chelator, ethyleneglycol-bis-(beta-aminoethyl ether)-N,N'-tetraacetic acid.
A treatment period as brief as 8 h in 10(-3) M EGTA completely blocks gravitropism in 70-80% of the treated coleoptiles of oats (Avena sativa L. cv. Garry) without inhibiting growth. Only about 10% of the plants perfused in water failed to exhibit gravitropism. Subsequent perfusion of EGTA-treated plants with calcium completely restores gravitropism; post-perfusion with water does not. After perfusion in water for 10 h, gravistimulated oat coleoptile segments show the same asymmetry of 45Ca distribution as reported earlier for non-perfused coleoptiles and sunflower hypocotyls. The degree of this asymmetry is reduced in those coleoptiles partially inhibited by perfusion in EGTA and is essentially absent in those coleoptiles completely inhibited by EGTA. The fact that calcium reverses the inhibitory effects of EGTA on gravitropism indicates that the inhibition was probably due to a reduction in the availability of free calcium required for one or more of the transduction steps of gravitropism.


Vasodilator therapy in chronic congestive heart failure.
Benefits from vasodilator therapy in patients with chronic heart failure are partly related to the severity of functional derangements. Agents with an arteriolar-dilating effect are more likely to be effective in patients with higher left ventricular outflow resistance. Vasodilators with primary venodilating properties are more likely to be effective in the presence of an increased ventricular preload. The mechanisms by which preload and left ventricular outflow resistance increase in patients with cardiac insufficiency are not well understood and may not be similar in all patients. Vasodilators also have the capacity to ameliorate myocardial metabolic functional abnormalities by influencing myocardial energetics, but the effects of different agents on coronary hemodynamics may not be uniform. Effects on renal hemodynamics may also vary, as may neurohumoral changes after therapy. Angiotensin-converting enzyme inhibitors have been shown to exert beneficial effects on both coronary and renal hemodynamics in patients with chronic heart failure, while producing favorable neurohumoral changes. These agents provide some advantages over direct-acting vasodilators in that myocardial oxygen consumption is decreased, myocardial metabolic function is improved, and norepinephrine and aldosterone levels are reduced. Further controlled studies are needed to assess the efficacy of angiotensin-converting enzyme inhibitors in relation to other vasodilators for the long-term management of these patients.


Morphometric analysis of pterygomaxillary region by using cone beam computed tomography.
Many complications during Le Fort I osteotomy are encountered during pterygomaxillary separation. The study aimed to evaluate the pterygomaxillary region in regards to the Le Fort I osteotomy using cone-beam computed tomography (CBCT) images. The CBCT images of 200 patients (100 males, 100 females) aged 18-78 years were evaluated measuring the thickness and width of the pterygomaxillary region, the location of the descending palatine artery, and the length of the pterygoid plates on the axial section. It has been determined that the distance between the descending palatine canal and the priform rim is longer in males (P=0.037). Medial plate was longer on the right (P=0.0001) and left (P=0.025) in females. The thickness of the pterygomaxillary region was longer in females (P=0.000). The distance between the pterygomaxillary fissure and the descending palatine canal was longer on the right (P=0.001). The pterygomaxillary region may have different anatomies that predispose to specific complications associated with Le Fort I osteotomy. Therefore, before surgery, the pterygomaxillary region should be examined with CBCT, and necessary precautions should be taken preoperatively considering the possible complications.


Novel Daple-like protein positively regulates both the Wnt/beta-catenin pathway and the Wnt/JNK pathway in Xenopus.
Wnt signaling pathways are essential in various developmental processes including differentiation, proliferation, cell migration, and cell polarity. Wnt proteins execute their multiple functions by activating distinct intracellular signaling cascades, although the mechanisms underlying this activation are not fully understood. We identified a novel Daple-like protein in Xenopus and named it xDal (Xenopus Daple-like). As with Daple, xDal contains several leucine zipper-like regions (LZLs) and a putative PDZ domain-binding motif, and can interact directly with the dishevelled protein. In contrast to mDaple, injection of xDal mRNA into the dorso-vegetal blastomere does not induce ventralization and acted synergistically with xdsh in secondary axis induction. XDal also induced expression of siamois and xnr-3, suggesting that XDal functions as a positive regulator of the Wnt/beta-catenin pathway. Injection of xDal mRNA into the dorso-animal blastomere, however, induced gastrulation-defective phenotypes in a dose-dependent manner. In addition, xDal inhibited activin-induced elongation of animal caps and enhanced c-jun phosphorylation. Based on these findings, xDal is also thought to function in the Wnt/JNK pathway. Moreover, functional domain analysis with several deletion mutants indicated that xDal requires both a putative PDZ domain-binding motif and at least one LZL for its activity. These findings with xDal will provide new information on the Wnt signaling pathways.


Behavioral determination of refractory periods of the brainstem substrates of self-stimulation.
The objective of this study was to estimate the refractory periods of the brainstem neurons responsible for self-stimulation behavior in the rat. In a first experiment, we tested the robustness of the double pulse technique used to estimate the refractory periods of reward-relevant neurons. We obtained estimates of the relative T-pulse effectiveness at a wide range of stimulation frequencies. The results of this experiment suggest that the refractory period estimates obtained with the behavioral version of the double pulse technique are not dependent on the arbitrary choice of the stimulation frequency. However, the use of stimulation frequencies higher than 100 Hz should preferably be avoided. In a second experiment, we applied the double pulse technique using C-pulse intensity higher than T-pulse intensity to estimate the refractory periods of the brainstem reward-relevant neurons. Using moveable electrodes, we tested 9 metencephalic and 7 mesencephalic sites in 4 animals. In the metencephalon, the most excitable reward-relevant neurons have absolute refractory periods of less than 0.6 and 0.8 ms and have a supernormal period that occurs at least between 5 and 10 ms after the initial excitation. The mesencephalic reward-relevant neurons were found to have more heterogeneous physiological characteristics. The most excitable cells in the mesencephalon have absolute refractory periods of less than 0.4 ms and have a supernormal period occurring as soon as 2.4 ms after the initial excitation. At some mesencephalic sites, we observed first an abrupt initial recovery followed by a plateau, followed by a renewed and continuous recovery, a pattern that was never observed in the metencephalon. The hypothesis of the contribution of two distinct sub-populations of reward-relevant neurons is proposed and the implication of monoaminergic pathways in reward is discussed.


Ligand modified cellulose fabrics as support of zinc oxide nanoparticles for UV protection and antimicrobial activities.
This work is a critical preventive study for providing a healthy life and enhancing people's safety at work in which introduces of highly efficient and durable UV-protection and antibacterial textiles. With this aim, ZnO nanoparticles are in situ synthesized on the modified cotton fabric to produce the multifunctional fabrics. Herein, the cotton fabric is oxidized by periodate and then treated by 4-aminobenzoic acid ligand (PABA). The modified cotton fabrics are characterized via X-ray powder diffraction, Fourier-transform infrared spectroscopy-attenuated total reflectance, scanning electron microscope, X-ray photoelectron spectroscopy, and thermogravimetric analysis. Moreover, the anti-bacterial, UV-protection, hydrophilicity, and mechanical properties of samples are investigated. The results show that pre-oxidization cotton fabric provides better active sites for the treatment with PABA. Then, PABA treatment provides significant sites for the growth of the ZnO nanoparticles and maintains cross-linking property between oxidized cellulosic fibers and the ZnO nanoparticles which improves the formation and durability of ZnO nanoparticles. The simultaneous sample treatment with ZnO and PABA had synergistic effects on UV protection, stability, and mechanical properties. Moreover, the ZnO PABA oxidized cotton fabrics show excellent UV-protection and significant antibacterial efficacy after 20 washing cycles and 100 abrasion cycles, which can be used in advanced protective textiles.


Information-Accessing Behavior during Zika Virus Outbreak, United States, 2016.
We used latent class analysis to examine Zika virus-related information-accessing behavior of US residents during the 2016 international outbreak. We characterized 3 classes of information-accessing behavior patterns: universalists, media seekers, and passive recipients. Understanding these patterns is crucial to planning risk communication during an emerging health threat.


Resolution of human immunodeficiency virus type 1 infection-related severe pulmonary hypertension in a very low-birth-weight infant.
Pulmonary arterial hypertension (PAH) affects approximately 0.5% of human immunodeficiency virus (HIV)-infected adults with poor prognosis. The effectiveness of highly active antiretroviral therapy for treatment of HIV-related PAH (HIV-PAH) remains controversial. Little is known about the incidence, clinical course, and therapy options for PAH in HIV-1-infected pediatric patients. Here, we report the case of a preterm infant with HIV-related life-threatening PAH, which resolved after initiation of highly active antiretroviral therapy.


[Acute, atraumatic changes of the lower respiratory tract in the child in thoracic roentgen imaging. Recognition and appreciation of radiological changes].
The diagnosis of acute, non-traumatic diseases of the lower respiratory tract requires exact knowledge of the specific anatomy, physiology and pathology of the pediatric chest. The absolutely and relatively smaller airways, as compared with those of adults, and the undeveloped collateral ventilation result in radiological appearances that are unique in children. Viral pneumonia is predominant only in small children up to an age of 2 years. With increasing age, there is a higher incidence of bacterial pneumonia. The differentiation of viral and bacterial etiology of a pneumonia is not possible on the basis of chest radiographs. In acute pediatric imaging, possible aspiration of foreign bodies has to be considered. Since most foreign bodies cannot be detected radiographically, indirect features such as hyperinflation or mediastinal shifts have to be evaluated. Primary lung tumors are rare in children. More common are metastases with known primary tumors. Neuroblastoma or lymphomas may mimic intrapulmonary pathologies.