Otitis media and linguistic incompetence.
In the examination of some effects of chronic middle ear disorders on the development of auditory processing skills in socioculturally disadvantaged children, three groups of children received a battery of tests assessing speech hearing in quiet, speech hearing in noise, auditory discrimination, phonemic synthesis, dichotic listening, verbal intelligence, and nonverbal intelligence. The experimental group consisted of 14 Australian aboriginal children with histories of chronic middle disorder, whereas two control groups, one European and the other aboriginal, each contained 18 children with normal middle ear function. The results demonstrated that chronic middle ear impairment not only restricts the development of some auditory processing skills, but distorts their integrational pattern.


The influence of FCGR2A and FCGR3A polymorphisms on the survival of patients with recurrent or metastatic squamous cell head and neck cancer treated with cetuximab.
FCGR2A-H131R and FCGR3A-V157F are single-nucleotide polymorphisms known to influence the outcome of patients treated with rituximab, cetuximab and trastuzumab. We investigated the impact of these polymorphisms on the clinical outcome of 103 patients with recurrent or metastatic squamous cell carcinoma of the head and neck treated with a platinum compound, fluorouracil and cetuximab as palliative first-line therapy. The survival of patients with FCGR2A-131H/H and/or FCGR3A-157V/V genotypes was significantly longer compared with patients carrying 131R and 157F alleles (median progression-free survival (PFS): 5.5 vs 4.1 months, P=0.02; median overall survival: 10.2 vs 7.2 months, P=0.04). In multivariate analysis, the FCGR2A and 3A genotypes as well as the time between initial diagnosis and relapse of disease not amenable to curative therapy remained the only independent prognostic factors for PFS. The results are in line with previous reports in colorectal cancer patients and confirm the possible value of genetic polymorphisms of immunocompetent cells for the success of cetuximab treatment.


Aligned MoO2/MoS2 and MoO2/MoTe2 Freestanding Core/Shell Nanoplates Driven by Surface Interactions.
Controlling the growth of two-dimensional (2D) transition metal dichalcogenides (TMDCs) is an important step toward utilizing these materials for either electronics or catalysis. Here, we report a new surface-templated growth method that enables the fabrication of MoO2/MoS2 and MoO2/MoTe2 core/shell nanoplates epitaxially aligned on (0001)-oriented 4H-silicon carbide and sapphire substrates. These heterostructures are characterized by a variety of techniques to identify the chemical and structural nature of the interface. Scanning electron microscopy shows that the nanoplates feature 3-fold symmetry indicative of epitaxial growth. Raman spectroscopy indicates that the MoO2/MoS2 nanoplates are composed of co-localized MoO2 and MoS2, and transmission electron microscopy confirms that the nanoplates feature MoO2 cores with 2D MoS2 coatings. Locked-coupled X-ray diffraction shows that the interfacial planes of the MoO2 nanoplate cores belong to the {010} and {001} families. This method may be further generalized to create novel nanostructured interfaces with single-crystal substrates.


New Zealand community mental healthcare provider experience in schizophrenia management with 3-monthly paliperidone palmitate.
To understand the impact of 3-monthly treatment with paliperidone palmitate on patient management, including non-adherence and relapse, from a psychiatrist and nurse perspective for 73 patients enrolled in a patient familiarisation programme (PFP) in New Zealand. An online questionnaire was sent to clinicians with at least 6 months of regular interaction with PFP patients. Questions addressed treatment effectiveness and patient management changes. Analyses are descriptive only and do not represent patient or carer perspectives. Seven psychiatrists, representing 58 of 73 (79.5%) of patients, and 17 nurses responded to the survey. Psychiatrists were satisfied with efficacy and tolerability and relapse prevention. Treatment goals were either 'met' (2/7; 28.6%) or 'exceeded' (5/7; 71.4%). The focus on adherence issues decreased and the focus on life areas and recovery goals increased. From the clinician perspective, 3-monthly paliperidone palmitate offers patients the potential to remain adherent and improve social functioning.


Novel fiber-dependent entry mechanism for adenovirus serotype 5 in lacrimal acini.
The established mechanism for infection of most cells with adenovirus serotype 5 (Ad5) involves fiber capsid protein binding to coxsackievirus-adenovirus receptor (CAR) at the cell surface, followed by penton base capsid protein binding to alpha(v) integrins, which triggers clathrin-mediated endocytosis of the virus. Here we determined the identity of the capsid proteins responsible for mediating Ad5 entry into the acinar epithelial cells of the lacrimal gland. Ad5 transduction of primary rabbit lacrimal acinar cells was inhibited by excess Ad5 fiber or knob (terminal region of the fiber) but not excess penton base. Investigation of the interactions of recombinant Ad5 penton base, fiber, and knob with lacrimal acini revealed that the penton base capsid protein remained surface associated, while the knob domain of the fiber capsid protein was rapidly internalized. Introduction of rabbit CAR-specific small interfering RNA (siRNA) into lacrimal acini under conditions that reduced intracellular CAR mRNA significantly inhibited Ad5 transduction, in contrast to a control (nonspecific) siRNA. Preincubation of Ad5 with excess heparin or pretreatment of acini with a heparinase cocktail each inhibited Ad5 transduction by a separate and apparently additive mechanism. Functional and imaging studies revealed that Ad5, fiber, and knob, but not penton base, stimulated macropinocytosis in acini and that inhibition of macropinocytosis significantly reduced Ad5 transduction of acini. However, inhibition of macropinocytosis did not reduce Ad5 uptake. We propose that internalization of Ad5 into lacrimal acini is through a novel fiber-dependent mechanism that includes CAR and heparan sulfate glycosaminoglycans and that the subsequent intracellular trafficking of Ad5 is enhanced by fiber-induced macropinocytosis.


Multiple triggers for hyperthermic fatigue and exhaustion.
It has been proposed that a critical body temperature exists at which muscle activation is impaired through a direct effect of high brain temperature decreasing the central drive to exercise, but other factors may also inhibit performance in the heat. An integrative physiological model is presented to stimulate research into mechanisms of hyperthermic fatigue and exhaustion.


Ungeremine and Its hemisynthesized analogues as bactericides against Flavobacterium columnare.
The Gram-negative bacterium Flavobacterium columnare is the cause of columnaris disease, which can occur in channel catfish ( Ictalurus punctatus ). In a previous study, the betaine-type alkaloid ungeremine, 1, obtained from Pancratium maritimum L. was found to have strong antibacterial activity against F. columnare. In this study, analogues of 1 were evaluated using a rapid bioassay for activity against F. columnare to determine if the analogues might provide greater antibacterial activity and to determine structure-activity relationships of the test compounds. Several ungeremine analogues were prepared by hydrochlorination of the alkaloid and by selenium dioxide oxidation of both lycorine, 7, and pseudolycorine, 8, which yielded the isomer of ungeremine, 3, and zefbetaine, 4, respectively. The treatment of lycorine with phosphorus oxychloride allowed the synthesis of an anhydrolycorine lactam, 5, showing, with respect to 1, the deoxygenation and oxygenation of C-2 and C-7 of the C and B rings, respectively. The results of the structure-activity relationship studies showed that the aromatization of the C ring and the oxidation to an azomethine group of C-7 of the B ring are structural features important for antibacterial activity. In addition, the position of the oxygenation of the C ring as well as the presence of the 1,3-dioxole ring joined to the A ring of the pyrrolo[de]phenanthridine skeleton also plays a significant role in imparting antibacterial activity. On the basis of 24-h 50% inhibition concentration (IC(50)) results, ungeremine hydrochloride, 2, was similar in toxicity to 1, whereas 5 had the lowest activity. Analogue 2 is soluble in water, which may provide the benefit for use as an effective feed additive or therapeutant compared to ungeremine.


The wayward implant: orbital silicone plate extrusion associated with squamous epithelial downgrowth and infection.
We report an unusual case of orbital implant migration in which the silicone plates were found to be enveloped in a pseudocapsule surprisingly infected and lined by squamous epithelium of probable conjunctival origin. An epithelial 'plug' found in the inferior fornix portion of the pseudocapsule might have been responsible for bacterial entry into the cavity. We discuss the literature regarding pseudocapsule formation around silicone implants and the phenomenon of capsular contracture. Both the infection and the epithelial downgrowth may have facilitated the implant migration.


Correlation of the Critical Care Pain Observation Tool and Numeric Rating Scale in Intensive Care Unit Patients.
We sought to determine the correlation between the Numeric Rating Scale (NRS) and Critical-Care Pain Observation Tool (CPOT) to determine whether clinical factors modified the relationship between NRS and CPOT assessments. We included nonventilated adults admitted to the MICU or SICU who could self-report pain and had at least 3 paired NRS and CPOT assessments. We performed Spearman correlation to assess overall correlation and performed proportional odds logistic regression to evaluate whether the relationship between NRS and CPOT assessments was modified by clinical factors. Nursing staff performed NRS and CPOT assessments every 4 h in 1302 patients, leading to 61,142 matched assessments. We found that the NRS and CPOT have a Spearman correlation coefficient of 0.56 and an intraclass correlation coefficient of 0.32 in intensive care unit patients. Factors that modified the relationship between the NRS and CPOT included the presence of delirium (P < .001) and lower mean daily Richmond Agitation Sedation Scale (<0.001). The correlation coefficient between the NRS and the CPOT was found to be 0.56. The presence of delirium, decreased level of arousal, modified the relationship between the NRS and CPOT. Self-reported and behavioral pain assessments cannot be used interchangeably in critically ill adults.


Association of CD4 T cell count and optimal timing of antiretroviral therapy initiation with immune reconstitution inflammatory syndrome and all-cause mortality for HIV-infected adults with newly diagnosed pulmonary tuberculosis: a systematic review and meta-analysis.
CD4 T cell count and optimal timing of antiretroviral therapy (ART) during tuberculosis (TB) treatment are challenging. We conducted a meta-analysis to assess the association of CD4 T cell count and timing of ART initiation with immune reconstitution inflammatory syndrome (IRIS) and all-cause mortality of patients co-infected with HIV/TB. We conducted an electronic search of clinical studies dated from January 1980 to December 2019 in PubMed and EMBASE. Randomized, controlled trials evaluating low-base CD4 T cell count (< 50 cells/μL) versus high-base CD4 T cell count (≥ 50 cells/μL), and/or early ART initiation (1 to 28 days after starting TB treatment) versus delayed ART initiation (≥ 28 days after starting TB treatment) were included. The primary endpoints were all-cause mortality and TB-related immune reconstitution inflammatory syndrome (IRIS-TB). The risk ratio (RR) was calculated as a measure of intervention effect. Mantel-Haenszel method was used to estimate the RR. Ten trials (n = 5226) were conducted in North America, Africa, and Asia. We found that low-baseline CD4 T cell count increased the incidence of TB-associated IRIS (RR, 1.47; 95% CI, 1.24-1.75; I2 = 58%) and all-cause mortality (RR, 2.42; 95% CI, 1.71-3.42; I2 = 41%) compared with high baseline CD4 T cell count, and early ART initiation increased the incidence of TB-associated IRIS compared with delayed ART initiation (RR, 1.80; 95% CI, 1.57-2.07; I2 = 74%). However, early ART initiation did not reduce all-cause mortality (RR, 0.91; 95% CI, 0.74-1.12; I2 = 49%) compared with delayed ART initiation. The present study demonstrates that low-baseline CD4 T cell count (< 50 cells/μL) in patients co-infected with TB-HIV increases the incidence of TB-associated IRIS and all-cause mortality. Early ART initiation (≤ 28 days) in patients co-infected with TB-HIV increases the incidence of TB-associated IRIS. However, evidence is insufficient to refute or support a survival benefit conferred by the comparison between early ART initiation (≤ 28 days) and delayed ART initiation.


Ras induces vascular smooth muscle cell senescence and inflammation in human atherosclerosis.
Vascular cells have a finite cell lifespan and eventually enter an irreversible growth arrest, cellular senescence. The functional changes associated with cellular senescence are thought to contribute to human aging and age-related vascular disorders. Ras, an important signaling molecule involved in atherogenic stimuli, is known to promote aging in yeast and cellular senescence in primary human fibroblasts. The aim of this study was to investigate the role of Ras-induced vascular smooth muscle cell (VSMC) senescence in atherogenesis. We introduced an activated ras allele (H-rasV12) into human VSMCs using retroviral infection. Introduction of H-rasV12 induced a growth arrest with phenotypic characteristics of cellular senescence, such as enlarged cell shapes and increases in expression of cyclin-dependent kinase inhibitors and senescence-associated beta-galactosidase (SA-beta-gal) activity. Activation of Ras drastically increased expression of proinflammatory cytokines, in part through extracellular signal-regulated kinase activation. To determine whether Ras activation induces cellular senescence in vivo, we transduced the adenoviral vector encoding H-rasV12 into rat carotid arteries injured by a balloon catheter. Introduction of Ras into the arteries enhanced vascular inflammation and senescence compared with mock-infected injured arteries. Moreover, SA-beta-gal-positive VSMCs were detected in the intima of advanced human atherosclerotic lesions and exhibited increased levels of extracellular signal-regulated kinase activity and proinflammatory cytokine expression. Our results suggest that atherogenic stimuli mediated by Ras induce VSMC senescence and vascular inflammation, thereby contributing to atherogenesis. This novel mechanism of atherogenesis may provide insights into a new antisenescence treatment for atherosclerosis.


Isolation and identification of an antioxidant enzyme catalase stimulatory compound from Garnoderma lucidum.
Antioxidant enzymes are scavenger reactive-oxygen intermediates and are involved in many cellular defense systems. We previously reported that a crude extract of Garnoderma lucidum, a medicinally potent mushroom, profoundly increased the catalase gene expression and enzyme activities in mouse livers (Park et al., J. Biochem. Mol. Biol. 34. 144-149, 2001). In this study, we elucidated the detailed mechanism whereby G. lucidum stimulates the catalase activity and expression. The major active fraction was isolated from G. lucidum and methyl linoleate was considered the most major component of the fraction. In order to determine whether methyl linoleate increases mRNA and protein synthesis of catalase, Northern and Western blot analyses were performed in vivo with methyl linoleate-treated mouse liver homogenate after feeding methyl linoleate to the mice. Northern and Western blot analyses of the crude liver homogenates in the mice that were administered methyl linoleate revealed that the expression catalase was significantly increased when compared to the untreated controls. In addition, the catalase protein levels and enzymatic activities increased in the mouse liver homogenates. These results suggest that methyl linoleate that is produced by G. lucidum stimulates the catalase expression at the transcription level.


Emergence of a KPC-3-Producing Escherichia coli ST69 as a Cause of Bloodstream Infections in Italy.
The spread of carbapenem-resistant gram negatives is a global emergency, and surveillance of new resistant clones is critical from both public health and clinical standpoints. Herein, we describe the emergence of a KPC-3-producing Escherichia coli ST69 as a cause of bloodstream infection in two Italian patients.


Free-roaming and surrendered dogs and cats submitted to a humane shelter in Wellington , New Zealand , 1999--2006.
To describe submissions of dogs and cats to an animal welfare shelter over a 6-year period, and to evaluate the association between the numbers of dogs and cats submitted per square kilometre, human population density, and standardised measures of socioeconomic deprivation. Details of free-roaming and surrendered dogs and cats presented to the Wellington shelter of the Society for the Prevention of Cruelty to Animals (SPCA) for the period 01 July 1999 to 28 February 2006 were recorded in a relational database. Data were plotted as counts of animals presented to the shelter each month as a function of calendar time. Kernel-smoothing techniques were used to describe the spatial distribution of capture location. The association between the number of dogs and cats submitted per square kilometre, human population density (both estimated at the mesh-block level), and mesh-block socioeconomic deprivation index were quantified using the Pearson product-moment correlation coefficient (r). The data comprised submission details for 3,709 dogs and 13,563 cats. There was a progressive decline in the number of dogs and cats submitted to the shelter over the study period, and a marked seasonal variation in submissions of cats. Submission density of dogs and cats was positively associated with human population density (Pearson's r=0.12; 95% CI=0.06-0.20 and 0.39; 95% CI=0.33-0.45, respectively) and socioeconomic deprivation (Pearson's r=0.12; 95% CI=0.05- 0.19 for both dogs and cats). Active approaches to free-roaming cat control by the Wellington SPCA should focus on the period June to September, prior to the feline breeding season, in population-dense and socioeconomically deprived areas. Composite analyses of submission details from all animal shelters in the Wellington region should allow factors associated with the distribution of free-roaming dogs and cats to be more precisely estimated.


Determinants of stillbirths in Ghana: does quality of antenatal care matter?
Each year, over two million babies die before they are born. Like maternal deaths, the great majority of these stillbirths occur in developing countries, with about a third of all cases worldwide in sub-Saharan Africa (SSA). Few studies have, however, examined the determinants of stillbirths in SSA. In addition, the emphases on promoting deliveries by skilled birth attendants and/or in health facilities to prevent maternal deaths, though important, may have undermined efforts to provide good quality antenatal care (ANC), which may have an additional role in preventing stillbirths. This study examines the factors associated with stillbirths in Ghana, focusing on the role of ANC quality. Data are from the Ghana Maternal Health Survey (N = 4,868)-a national survey of women of reproductive age. The main analysis includes women who had a pregnancy ending in a live birth or stillbirth in the five years preceding the survey and who received ANC at least once. ANC quality is measured by an index based on receipt (or otherwise) of nine antenatal services during the last pregnancy, including education about pregnancy complications; with receipt of at least of eight services classified as higher quality ANC. Stillbirths refer to babies born dead at seven or more months of pregnancy. Analytic techniques include multilevel logistic regression, with moderation and mediation analysis to examine conditional and intervening effects respectively. Higher quality ANC decreases the odds of a stillbirth by almost half after accounting for other factors, including the type of delivery provider and facility. Educating pregnant women about pregnancy complications contributes significantly to this difference by ANC quality. The type of delivery facility and provider account for a small proportion (14 %) of the ANC quality effect on stillbirths and a larger proportion of the rural/urban difference (27 %) in stillbirths. Completing the recommended four antenatal visits decreases the odds of a stillbirth. Having a pregnancy complication, a multiple gestation, a past stillbirth, or a sister who died from pregnancy complications increases the odds of a stillbirth. Good quality ANC can improve birth outcomes in two ways: directly through preventative measures, and indirectly through promoting deliveries in health facilities where complications can be better managed. Targeted programs and policies to increase ANC quality, including adequately educating women on pregnancy complications, will help improve birth outcomes in Ghana, and in SSA as a whole.


High-frequency, but not low-frequency, transcutaneous electrical nerve stimulation reduces aspartate and glutamate release in the spinal cord dorsal horn.
Transcutaneous electrical nerve stimulation (TENS) is a commonly utilized non-pharmacological treatment for pain. Studies show that low- and high-frequency TENS utilize opioid, serotonin and/or muscarinic receptors in the spinal cord to reduce hyperalgesia induced by joint inflammation in rats. As there is an increase in glutamate and aspartate levels in the spinal cord after joint inflammation, and opioids reduce glutamate and aspartate release, we hypothesized that TENS reduces release of glutamate and aspartate in animals with joint inflammation by activation of opioid receptors. Using microdialysis and HPLC with fluorescence detection, we examined the release pattern of glutamate and aspartate in the dorsal horn in response to either low-frequency (4 Hz) or high-frequency (100 Hz) TENS. We examined the effects of TENS on glutamate and aspartate release in animals with and without joint inflammation. High-frequency, but not low-frequency, TENS significantly reduced spinal glutamate and aspartate in animals with joint inflammation compared with levels in those without joint inflammation. The reduced release of glutamate and aspartate by high-frequency TENS was prevented by spinal blockade of delta-opioid receptors with naltrindole. Thus, we conclude that high-frequency TENS activates delta-opioid receptors consequently reducing the increased release of glutamate and aspartate in the spinal cord.


Characteristic monitoring of groundwater-salt transportation and input-output in inland arid irrigation area.
The rules of microscopic water-salt transportation can be revealed and the impact on the macroscopic water and soil resources can be further predicted by selecting a typical study area and carrying out continuous monitoring. In this paper, Jingtaichuan Electrical Lifting Irrigation District in Gansu Province (hereinafter called as JingDian irrigation district (JID)) located at the inland desert region of northwest China was selected as study area. Based on the groundwater-salt transportation data of representative groundwater monitoring wells in different hydrogeological units, the groundwater-salt evolution and transportation tendency in both closed and unclosed hydrogeological units were analyzed and the quantity relative ratio relationship of regional water-salt input-excretion was calculated. The results showed that the salt brought in by artificial irrigation accounts for the highest proportion of about 63.99% and the salt carried off by the discharge of irrigation water accounts for 66.42%, namely, the water-salt evolution and transportation were mainly controlled by artificial irrigation. As the general features of regional water-salt transportation, groundwater salinity and soil salt content variation were mainly decided by the transportation of soil soluble salt which showed an obvious symbiosis gathering regularity, but the differentiation with insoluble salt components was significant in the transportation process. Besides, groundwater salinity of the unclosed hydrogeological unit presented a periodically fluctuating trend, while the groundwater salinity and soil salt content in water and salt accumulation zone of the closed hydrogeological unit showed an increasing tendency, which formed the main occurrence area of soil secondary salinization.


Modulation of bacterial association to HeLa cell cultures by cell density and by chlamydial infection.
The effect of cell density on the rate of association of Escherichia coli and Staphylococcus aureus by monolayer cultures of HeLa 229 cells was investigated. Radioactively labeled bacteria were incubated with sparsely and densely plated cells. The rate of bacterial uptake was 10- to 20-fold higher in sparse cultures. Kinetic analysis of data with different multiplicities of input bacteria showed that the Km of the reaction was unaltered, whereas the Vmax was inversely related to cell density. Pretreatment of HeLa cultures with dibutyryl adenosine 3',5'-phosphate had little effect on the rate of bacterial association. The simultaneous presence of an obligately parasitic bacterium, Chlamydia trachomatis LGV434, enhanced the Vmax of association of E. coli and S. aureus. This effect was more pronounced in dense HeLa cell cultures. Heat-inactivated chlamydiae were unable to modify the association. Enhanced association persisted for at least 3 h after infection with chlamydiae.


Cross-Cultural Validation of the Scale of Oral Health-Related Outcomes for 5-Year-Old-Children with a Low-Income Sample from the Dominican Republic.
To conduct a thorough psychometric assessment and validation of a Spanish-adapted version of the Scale of Oral Health-Related Outcomes for 5-Year-Old-Children (SOHO-5). The sample consisted of 69 children aged 6 and 7 years attending a public school from a low-income community in the Dominican Republic. Outcomes consisted of SOHO-5 test scores and caries lesion severity scores, with the latter measured according to the International Caries Detection and Assessment System criteria. The IBM SPSS Statistics 20 and Mplus 7.4 programs were used for the statistical analyses. A confirmatory factor analysis revealed an excellent fit for the theoretical one-factor structure of the SOHO-5, with all the items having high loadings on this latent factor. In addition, the SOHO-5 was able to significantly explain a large amount of variance (37%) in caries lesion severity (P < 0.001), while its scale scores had good internal consistency reliability (Cronbach's alpha [α] = 0.85, 95% confidence interval [CI] 0.79-0.90). Further, the SOHO-5 could identify children with moderate and extensive caries lesions (area under the receiver operating characteristic curve = 0.82, 95% CI 0.70-0.94, P < 0.001). The current findings highlight the good psychometric properties and criterion-related validity of the Spanish-adapted SOHO-5 for young children who come from impoverished backgrounds.


Lactating sows and suckling piglets preferentially incorporate RRR- over all-rac-alpha-tocopherol into milk, plasma and tissues.
Synthetic vitamin E, all-rac-alpha-tocopherol, contains eight different stereoisomers, only one of which, RRR-alpha-tocopherol, occurs naturally. The objective of this investigation was to evaluate the relative abilities of these two vitamin E forms to enrich piglet tissues when fed as alpha-tocopheryl acetates to sows during pregnancy and lactation. alpha-Tocopherol delivery to fetuses and to suckling piglets was monitored by feeding 150 mg each of d(3)-RRR-alpha- and d(6)-all-rac-alpha-tocopheryl acetate to three pregnant sows daily from 7 d before to 7 d after giving birth. Labeled and unlabeled vitamin E concentration ratios were measured in sow plasma and milk, and in piglet (n = 9) plasma and tissues at birth, 7 and 21 d. At birth, despite elevated sow plasma deuterated alpha-tocopherol concentrations, no labeled alpha-tocopherol was detected in piglet plasma or tissues. Sow plasma and milk d(3)-alpha- to d(6)-alpha-tocopherol concentrations were 2:1, leading to a 2:1 ratio in suckling piglet plasma and tissues. In piglets at d 7 compared with birth, most tissues contained a 10-fold increase in total alpha-tocopherol; the highest deuterated vitamin E concentrations were in the liver, followed by the lung, heart, kidney, muscle, intestine and brain. In conclusion, pigs discriminate between RRR- and all-rac-alpha-tocopherol with a preference for RRR-alpha-tocopherol; thus, the official bioequivalence ratio of 1.36:1 RRR- to all-rac-alpha-tocopherol is underestimated. After initiation of suckling, piglet plasma and tissues demonstrated a dramatic increase in vitamin E concentrations, emphasizing the limited placental vitamin E transfer and the importance of milk for enhancing the vitamin E status of the newborn.


[The Number of Deliberate Self-Poisoning Suicide Attempts in the First Year of the Covid-19 Epidemic in Budapest and Pest County].
In contrast to most other countries, in Hungary, suicide rates increased significantly in the first year (March to December 2020) of the COVID-19 epidemic. Worldwide, the burden of emergency health care tended to decrease in the first period of the pandemic. The main goal of the present research was to assess how the number of suicidal deliberate self-poisoning has changed in the first two years of the pandemic compared to the trend of the previous years (before March 2020) in the capital of Hungary, Budapest, and in Pest County (population approx. 3 million). In our retrospective cross-sectional study, we analyzed the results of emergency psychiatric evaluations of patients admitted to the Péterfy Hospital Emergency Department and Clinical Toxicology due to self-intoxication. From the data stored in the hospital's electronic health care system, we recorded two variables: suicidal self-poisoning, that is, suicide attempt, and the gender of the patient. Interrupted time series analysis was used, which relied on negative binomial regression estimates. In addition, the leveling in the trends was examined by changepoint detection. In males, suicide attempts decreased by 16.6% compared to the pre-pandemic period (p<0.001). A similar and significant decrease was observed in females and the overall population. The trend change took place in August 2020 for women and the total population, and in October for men. It is suggested that people who have undergone a non-violent drug self-poisoning suicide attempt are less likely to call for help, such as an ambulance. Alternatively, fewer had attempted suicide because they did not want to be hospitalized. This hypothesis is supported by the fact that the change in the examined trend (August and October) coincides with the beginning of the second wave of the epidemic in Hungary.


Functional dissociation between fornix and hippocampus in spatial conditional learning.
Do lesions of the fornix or the hippocampus impair the performance of spatial conditional associative learning tasks, and to what extent does damage to these brain structures result in comparable deficits in this type of spatial behavior? The available evidence is not clear. In the present study, rats with lesions of the fornix, hippocampus, and normal control animals were trained on two spatial-visual conditional learning tasks in which they had to form arbitrary associations between visual stimuli and the context in which these stimuli were embedded. In one condition, rats were required to choose stimulus X in place A and stimulus Y in place B, and there was no overlap in the contents of the two scenes. In the other condition, the animal approached the same scene from two different directions and had to select stimulus X when the scene was viewed from perspective A and to select stimulus Y when the scene was viewed from perspective B. Rats with fornix transection were able to learn both conditional tasks at a rate comparable to that of normal control animals, but rats with hippocampal damage were severely impaired under both conditions. The findings extend the range of tasks known to be sensitive to damage of the hippocampus. In addition, the results argue that the fornix is not necessary for the acquisition of certain spatial conditional learning tasks and that this brain structure cannot be used as an indicator of hippocampal dysfunction under all learning situations.


Unimproved chest pain in patients with minimal or no coronary disease: a behavioral phenomenon.
Patients with chest pain and minimal or no coronary disease have a good prognosis for survival, yet many continue to have pain. In our experience with 821 medically treated patients there were three cardiac deaths (0.3%) and two nonfatal myocardial infarctions (0.2%) in the first year after angiography, which had revealed insignificant (less than 75% narrowing of the luminal diameter) or no coronary artery stenosis. In a subset of 548 patients selected with no apparent systematic difference from the inception cohort of 821 patients, there was complete absence of chest pain in 178 (33%) patients but 155 (28%) had similar or worse pain. From an analysis of clinical history and catheterization data entered in a stepwise logistic regression function, unimproved chest pain was significantly associated with female sex (p = 0.01) and an index of five chest pain descriptors (p = 0.0005). After adding selected behavioral variables available for a representative sample of 217 patients, a high hypochondriasis score (scale I from the Minnesota Multiphasic Personality Inventory) became the strongest determinant of continued pain (p less than 0.0001). In our experience, an exaggerated preoccupation with personal health is prospectively associated with continued chest pain in patients with minimal or no coronary disease.


The technique of detecting systolic and diastolic pressure from the transducer output of a PC-based blood pressure monitoring system.
A pressure to voltage transducer is used along with a cuff, in a PC-based blood pressure and pulse rate monitoring system for human body. During the blood pressure measurement cycle, the output voltage of the pressure to voltage transducer is recorded digitally using a data acquisition system. The recorded data are then analyzed using software routines to determine the blood pressure and pulse rate of the person under test. However, it is difficult to identify the points of systole and diastole correctly from the recorded data. This paper presents the technique that may be used to determine the systolic and diastolic pressure from the collected data.


Mezlocillin and ticarcillin alone and combined with gentamicin in the treatment of experimental Enterobacter aerogenes endocarditis.
The efficacies of mezlocillin and ticarcillin, each alone and in combination with gentamicin, in the therapy of experimental left-sided Enterobacter aerogenes endocarditis in rabbits were compared. Each beta-lactam was administered intramuscularly at a dose of 180 mg/kg every 6 h either alone or with gentamicin (1.7 mg/kg intramuscularly every 8 h). Bacterial populations at the start of therapy (7 days after initiation of infection) were 9 to 10 log10 CFU/g of vegetation. Ticarcillin produced concentrations in serum that were twice those produced by mezlocillin, but the therapeutic ratios of mezlocillin and ticarcillin (ratio of peak level in serum to MBC) were the same. All of the therapeutic regimens given for either 5 or 10 days were effective in reducing vegetation counts when compared with the untreated controls (P less than 0.01 for all comparisons), except mezlocillin alone and ticarcillin alone, which caused insignificant reductions in counts after 5 days of therapy (P greater than 0.05). After 10 days of therapy, the only regimen that was significantly different from another was that of mezlocillin plus gentamicin, which was significantly better than that of ticarcillin alone (P less than 0.01). These studies document that mezlocillin and ticarcillin were both effective in reducing the numbers of E. aerogenes CFU in vegetations in rabbits with experimental endocarditis when the drugs were given over a prolonged course. More rapid and extensive reduction in vegetation counts was achieved with combinations of an aminoglycoside plus mezlocillin or ticarcillin. Mortality was significantly less among rabbits treated with mezlocillin plus gentamicin.


Expansion of a plasmid classification system for Gram-positive bacteria and determination of the diversity of plasmids in Staphylococcus aureus strains of human, animal, and food origins.
An expansion of a previously described plasmid classification was performed and used to reveal the plasmid content of a collection of 92 Staphylococcus aureus strains of different origins. rep genes of other genera were detected in Staphylococcus. S1 pulsed-field gel electrophoresis (PFGE) hybridizations were performed with 18 representative S. aureus strains, and a high number of plasmids of different sizes and organizations were detected.


Three-dimensional acoustic vector field model using Gaussian beam tracing.
A three-dimensional acoustic vector field model was developed using Gaussian beam tracing. The field at any location is computed by coherently summing all contributing beams, where the beam equation of particle velocity depends only on beam width and eikonal. A deep-sea long-range sound propagation experiment in the South China Sea was analyzed using vector hydrophone measurements of particle velocity and sound pressure. The results were compared with the model predictions, indicating that beam tracing is effective in predicting sound pressure and acoustic vector fields in deep water.


De novo prediction of cell-type complexity in single-cell RNA-seq and tumor microenvironments.
Recent single-cell transcriptomic studies revealed new insights into cell-type heterogeneities in cellular microenvironments unavailable from bulk studies. A significant drawback of currently available algorithms is the need to use empirical parameters or rely on indirect quality measures to estimate the degree of complexity, i.e., the number of subgroups present in the sample. We fill this gap with a single-cell data analysis procedure allowing for unambiguous assessments of the depth of heterogeneity in subclonal compositions supported by data. Our approach combines nonnegative matrix factorization, which takes advantage of the sparse and nonnegative nature of single-cell RNA count data, with Bayesian model comparison enabling de novo prediction of the depth of heterogeneity. We show that the method predicts the correct number of subgroups using simulated data, primary blood mononuclear cell, and pancreatic cell data. We applied our approach to a collection of single-cell tumor samples and found two qualitatively distinct classes of cell-type heterogeneity in cancer microenvironments.


Kinetics of the Photoexcited States in Thin Films of Metallo-Supramolecular Polymers With Ditopic Thiophene-Bridged Terpyridine Ligands.
Managing the excited-state decay by a supramolecular structure is a crucial issue for organic photovoltaics. We show that in thin films of metallo-supramolecular polymers made of bis(terpyridine-4'-yl)terthiophenes and Z n 2 + coupling ions, the photoexcited states generated by ultrashort laser pulses at the wavelength of 440 nm decay by the bi-molecular annihilation predominantly controlled by the Förster transfer between singlet states. During this bi-molecular annihilation of singlet states, intermediate hot triplet pairs are formed, which subsequently dissociate into long-living diffusing triplet states. It explains a significant shortening of the triplet state rise time with increasing pump fluence. The diffusion coefficient of triplets showed power-law time dependence, with its exponent proportional to the pump fluence, decreasing thus the diffusivity of triplets.


Patient-Reported Outcome Measures in Liver and Gastrointestinal Cancer Randomized Controlled Trials.
For many years, outcomes such as mortality and morbidity were the standard for evaluating oncological treatment effectiveness. With the introduction of patient-reported outcome measures (PROMs), the focus shifted from a mere extension of a patient's life or release from disease to the improvement of a multilayered concept of health, decisively affecting life satisfaction. In this study, we deal with the topic of PROMs in liver and gastrointestinal randomized controlled trials. The final database included 43 papers reporting results of randomized controlled trials (RCTs) for liver or gastrointestinal cancer interventions where one of the primary or secondary outcomes was a health-related quality of life measure. The most often used PROM was the European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC QLQ-C30) for both liver cancer and gastrointestinal cancer (in 62% of gastrointestinal cancer studies and 57% of liver cancer studies). For the gastrointestinal cancer group, the QLQ-STO22, a cancer-specific extension of the QLQ-C30, was the second most commonly used PROM. In liver cancer, the generic PROM Short Form 36 and the EORTC QLQ-HCC18, a cancer-specific extension of the QLQ-C30, were the second most commonly used PROMs. We found that RCTs often do not include comprehensive quality-of-life measures. When quality of life is part of an RCT, it is often only a secondary outcome. For a holistic view of the patient, a stronger integration and weighting of patient-reported outcomes in RCTs would be desirable.


Effect of prenatal testosterone administration on palmar dermatoglyphic intercore ridge counts of rhesus monkeys (Macaca mulatta).
Dermatoglyphic ridge counts of the prints of 59 rhesus monkeys (Macaca mulatta) whose mothers had been treated with injections of testosterone during their pregnancies were studied to determine the effect of the day the hormone began to be administered, the amount of hormone administered, and the number of days of hormone administration upon the dermatoglyphic variation of the offspring. Of the three hormone variables, only the day of beginning administration (STARTDAY) was significantly associated with dermatoglyphic variation, and its positive significance was demonstrated with the ridge counts of Area I on both the left and right hand, Area II of the left hand, and the total ridge counts of both hands. These results are discussed within the context of the timing of the dermatoglyphic window, and the differences in the findings between the monkey and earlier human studies are addressed.


Rituximab in Refractory Myasthenia Gravis: Experience in a Single Healthcare Center in Mexico.
Ten to fifteen percent of patients with myasthenia gravis (MG) have treatment-refractory disease. In short series and case reports, rituximab has proven to be effective in refractory MG. A retrospective, longitudinal study was conducted. Recruitment was performed in an MG cohort from a single third-level healthcare center in Mexico. The selection included refractory MG patients that were treated with rituximab. Response after rituximab therapy was assessed with MG composite score (MGCS) and prednisone dose reduction at 6, 12, and 18 months after initiation. Wilcoxon signed-rank test was used to evaluate differences between related groups for non-continual variables. P<0.05 was considered statistically significant. Ten patients (7%) fulfilled criteria for refractory MG, and eight of them were treated with rituximab. The mean age at MG diagnosis was 25.5 (±2) years, with a female predominance (75%). All our patients (100%) had positive acetylcholine receptor (AchR) antibodies. The median MG duration was six years (interquartile range [IQR] 4.2-6) before rituximab initiation. All patients were previously treated with azathioprine and 50% additionally with cyclophosphamide. The median prednisone doses before rituximab treatment and 18-month follow-up were 50 mg (IQR 30-50 mg) and 10 mg (IQR 0-20 mg), respectively (p=0.011). The median baseline MGCS and at 18-month follow-up were 19.5 (IQR 11-31) and 6 (IQR0-16), respectively (p = 0.012). Rituximab appears to be associated with clinical improvement and prednisone dose reduction in Latin-American patients diagnosed with anti-AchR MG. Our findings need to be interpreted in light of the limitations mentioned.


Socioeconomic gradient in use of statins among Danish patients: population-based cross-sectional study.
Socioeconomic inequalities in statin use are a public health concern but they may also confound observational studies of statins' effectiveness. We conducted a population-based cross-sectional study in Denmark to examine the association between socioeconomic status (SES) and statin use. We obtained data on socioeconomic status of all persons in North Jutland County, Denmark, between 1995 and 1999 from the Prevention Registry at Statistics Denmark. Data on filled statin prescriptions were identified through the County Prescription Database. We compared the 1-year prevalence proportions of statin use for different socioeconomic groups, adjusted for age and urbanization. Separate analyses were done for patients with a history of cardiovascular disease as recorded in the County Hospital Discharge Registry. Among men with cardiovascular disease, statin use in 1995 was higher in those with the highest socioeconomic status (adjusted relative prevalence proportion (RPP) among top managers 1.86, 95% CI: 1.17-2.96), and lower among retired men (RPP (95% CI) 0.63 [0.43-0.93] in old-age pensioners, and 0.66 [0.45-0.98] in the early retired), when compared with basic-level workers. The socioeconomic differences in statin use among men decreased in magnitude over time but remained throughout the study period. We found no clear social gradient in statin use among women. Even in a health care system that claims to ensure a high degree of equity in medical care, we found clear indications of a socioeconomic gradient in statin use among men in the years after the launching of these drugs.


Are commercial probiotics and prebiotics effective in the treatment and prevention of honeybee nosemosis C?
The study was conducted to investigate the effect of Lactobacillus rhamnosus (a commercial probiotic) and inulin (a prebiotic) on the survival rates of honeybees infected and uninfected with Nosema ceranae, the level of phenoloxidase (PO) activity, the course of nosemosis, and the effect on the prevention of nosemosis development in bees. The cells of L. rhamnosus exhibited a high rate of survival in 56.56 % sugar syrup, which was used to feed the honeybees. Surprisingly, honeybees fed with sugar syrup supplemented with a commercial probiotic and a probiotic + prebiotic were more susceptible to N. ceranae infection, and their lifespan was much shorter. The number of microsporidian spores in the honeybees fed for 9 days prior to N. ceranae infection with a sugar syrup supplemented with a commercial probiotic was 25 times higher (970 million spores per one honeybee) than in a control group fed with pure sucrose syrup (38 million spores per one honeybee). PO activity reached its highest level in the hemolymph of this honeybee control group uninfected with N. ceranae. The addition of probiotics or both probiotics and prebiotics to the food of uninfected bees led to the ~2-fold decrease in the PO activity. The infection of honeybees with N. ceranae accompanied an almost 20-fold decrease in the PO level. The inulin supplemented solely at a concentration of 2 μg/mL was the only administrated factor which did not significantly affect honeybees' survival, the PO activity, or the nosemosis infection level. In conclusion, the supplementation of honeybees' diet with improperly selected probiotics or both probiotics and prebiotics does not prevent nosemosis development, can de-regulate insect immune systems, and may significantly increase bee mortality.


[Effect of an on-line health promotion program connected with a hospital health examination center on health promotion behavior and health status].
The purpose of this study was to evaluate the effect of an On-line health promotion program connected with a hospital health examination center. Based on contents developed, the www.kmwellbeing.com homepage was developed. The research design was a one group pretest-posttest design. Seventy-three clients participated in this study. The data were collected from January 3 to June 30, 2005. As a way of utilizing the homepage, this paper attempted to measure the change of pre and post program health promotion behavior and health status (perceived health status, objective health index-blood pressure, pulse, total cholesterol, blood sugar, waist flexibility, grip strength and lower extremity strength). Data were analyzed by descriptive statistics and paired t-test with the SPSS/Win 12.0 program. There were significant differences of perceived health status, systolic BP, waist flexibility and grip strength. However, there were no significant differences in health promotion behavior, diastolic BP, pulse, lower extremity strength, blood sugar and total cholesterol between pre program and post program. It is expected that an on-line health promotion program connected with a hospital health examination center will provide an effective learning media for health education and partially contribute to client's health promotion. A strategy, however, is needed to facilitate the continuous use of the on-line health promotion program for adult clients.


Expression of immunoglobulin receptors with distinctive features indicating antigen selection by marginal zone B cells from human spleen.
Marginal zone (MZ) B cells, identified as surface (s)IgM(high)sIgD(low)CD23(low/-)CD21(+)CD38(-) B cells, were purified from human spleens, and the features of their V(D)J gene rearrangements were investigated and compared with those of germinal center (GC), follicular mantle (FM) and switched memory (SM) B cells. Most MZ B cells were CD27(+) and exhibited somatic hypermutations (SHM), although to a lower extent than SM B cells. Moreover, among MZ B-cell rearrangements, recurrent sequences were observed, some of which displayed intraclonal diversification. The same diversifying sequences were detected in very low numbers in GC and FM B cells and only when a highly sensitive, gene-specific polymerase chain reaction was used. This result indicates that MZ B cells could expand and diversify in situ and also suggested the presence of a number of activation-induced cytidine deaminase (AID)-expressing B cells in the MZ. The notion of antigen-driven expansion/selection in situ is further supported by the VH CDR3 features of MZ B cells with highly conserved amino acids at specific positions and by the finding of shared ("stereotyped") sequences in two different spleens. Collectively, the data are consistent with the notion that MZ B cells are a special subset selected by in situ antigenic stimuli.


Microbiological data for patients with febrile neutropenia.
The pattern of bacterial infections and antimicrobial susceptibility has changed significantly during the past 20-30 years. The causative organisms for bacteremia or fungemia identified at Kinki University Hospital in 1985-1996 were compared with the isolates identified during 1997-2002. The prevalence of gram-negative organisms decreased, whereas the prevalence of gram-positive organisms increased. Staphylococcal species predominated in the second period, accounting for 22% of isolates, and methicillin-resistant Staphylococcus aureus (MRSA) increased from 5% to 14% of isolates. Pseudomonas aeruginosa ranked second, although the prevalence decreased in the second period compared with the first. Candida species were also relatively frequent (11%). Enterococcal species had an 8% prevalence. A comparison of all culture isolates showed that gram-negative isolates still predominated among the general patient population, whereas almost equal prevalence was observed in patients with hematological diseases. MRSA was the organism most frequently isolated in the general patient population, followed by P. aeruginosa. Among staphylococcal species, MRSA accounted for as much as 90% of isolates.


Pulmonary hypertension after splenectomy in hereditary stomatocytosis.
Hereditary stomatocytosis is an autosomal dominant, congenital hemolytic form of anemia, and thromboembolic complications may ensue after a splenectomy is performed in a patient with hereditary stomatocytosis. However, little is known about the relationship between pulmonary hypertension and hereditary stomatocytosis. We describe here a rare case of a patient with hereditary stomatocytosis who developed pulmonary hypertension due to thromboembolic disease after splenectomy. At the first presentation, he was diagnosed with hemolytic anemia, but the cause was unknown, and he was also diagnosed with pulmonary hypertension. Thereafter, we linked his pulmonary hypertension with hemolytic anemia because his red blood cells appeared as leptocytes, acanthytes, and stomatocytes on scanning electron microscopy. It is important to confirm the diagnosis of hemolytic anemia, and splenectomy should be performed with due consideration of whether patients have hemolytic anemia.


Methodological Considerations in Salivary Proteomics for Periodontal Research-A Review.
The diagnosis and management of periodontal diseases can be enhanced by the identification of biomolecules which can predict disease susceptibility, indicate current disease activity, and monitor response to therapy. Salivary proteomics is a major avenue in the ongoing search for a biomarker in periodontal research. Saliva is a valuable diagnostic vehicle which "mirrors" oral and systemic health and disease. Standardized methods of saliva sampling and processing will increase diagnostic test accuracy and decrease bias in measurements. Prominent databases such as PubMed/Medline, PMC, Scopus, and Google Scholar were searched and literature evidence from January 2000 till September 2022 were studied to identify the methodological considerations employed in salivary proteomics for periodontal research. Evidence and recommendations in this regard were collated into this narrative review. The methods of saliva collection and processing presented in this review will help researchers conduct salivary proteomic studies with standardized protocols.


Placental Pathology Associated with Household Air Pollution in a Cohort of Pregnant Women from Dar es Salaam, Tanzania.
Smoke from the burning of biomass fuels has been linked with adverse pregnancy outcomes such as low birth weight, stillbirth, and prematurity. To identify potential underlying mechanisms of adverse perinatal outcomes, we explored the association of placental pathology with household air pollution in pregnant women from urban/periurban Tanzania who cook predominantly with charcoal. Between 2011 and 2013, we measured personal exposures to fine particulate matter (PM2.5) and carbon monoxide (CO) over 72 hr among a cohort of Tanzanian pregnant women. Placentas were collected after delivery for examination. Placental pathologies of inflammatory, hypoxic, ischemic/hypertensive, infectious and thrombotic etiologies were diagnosed, blinded to exposure levels. Using multiple logistic regression, we explored the association of PM2.5 and CO exposure with placental pathology. One hundred sixteen women had personal air exposure measurements and placental histopathology available for analysis. PM2.5 and CO exposures were moderate [geometric means (GSD) were 40.5 μg/m3 (17.3) and 2.21 ppm (1.47) respectively]; 88.6% of PM2.5 measurements exceeded World Health Organization air quality guidelines. We observed an increase in the odds (per 1-unit increase in exposure on the ln-scale) of fetal thrombotic vasculopathy (FTV) both with increasing PM2.5 [adjusted odds ratio (aOR) = 5.5; 95% CI: 1.1, 26.8] and CO measurements (aOR = 2.5; 95% CI: 1.0, 6.4) in adjusted models only. FTV also was more common among pregnancies complicated by stillbirth or low birth weight. Fetal thrombosis may contribute to the adverse outcomes associated with household air pollution from cook stoves during pregnancy. Larger studies are necessary for confirmation. Citation: Wylie BJ, Matechi E, Kishashu Y, Fawzi W, Premji Z, Coull BA, Hauser R, Ezzati M, Roberts D. 2017. Placental pathology associated with household air pollution in a cohort of pregnant women from Dar es Salaam, Tanzania. Environ Health Perspect 125:134-140; http://dx.doi.org/10.1289/EHP256.


Female sexual functioning during pregnancy.
Sexuality is a fundamental, biological function of every human body, regardless of age, gender or race. However, the need for intimacy, closeness and sexual activity changes over time; it is influenced by the age, experience, physical and health condition. Sex is also one of the most important domains of the quality of life (QoL). However, this topic is still uneasy and rarely discussed, even though female sexual dysfunction (FSD) is a common problem, which affects 20% to 50% of women. Moreover, women experience processes that do not affect men, such as menstruation, pregnancy and menopause. In this review we focused on pregnancy, since sexual life of pregnant women alters during pregnancy due to the physiological, anatomical and hormonal changes in her body. Nonetheless, woman can keep having sex during a physiological pregnancy, but this issue is rarely addressed by physicians-gynecologists. Therefore, the aim of this manuscript was to discuss female sexuality during pregnancy.


Informal Convergence at Major Emergency Incidents in Kenya.
"Convergence behavior" is the informal, spontaneous movement of people, messages, and supplies toward a major emergency incident area. This form of movement brings needed aid to many victims, but at the same time the resultant congestion makes organization and control of the rescue and relief efforts more difficult. Whenever a major emergency incident occurs in Kenya, typically a huge crowd of sightseers and personnel converge at the scene. This report provides a review of informal convergence behavior in Kenya during major emergency incidents over the last 15 years (1998-2013) and some of the risks that have been associated with this phenomenon. It also provides some recommendations that have been successfully implemented in other countries, as well as in rare instances in Kenya, to control informal convergence behavior.


Application of multivariate analysis to the screening of molecularly imprinted polymers (MIPs) for ametryn.
Among the solid-phase extraction (SPE) techniques, a novel system for a triazine herbicide named ametryn, has been developed based on a molecular imprinted polymer (MIP) phase. Through this method, the synthesis of the complementary to ametryn MIP was accomplished and the factors influencing its efficiency have been optimized. Through the optimization process, the type and the amounts of functional monomer and solvents, template amount, cross-linker, initiator as well as the polymerization temperature were considered to be evaluated. Based on the obtained results, the optimum conditions for the efficient polymerized sorbent, considering the recovery efficiency were solvent: acetonitrile, 6.41 mL; monomer: methacrylic acid, 5.41 mmol; template: 1.204 mmol; cross-linker: 27.070 mmol; initiator: 2.03 mmol; temperature: 40.86 degrees C. The optimum molar ratio among the template, monomer and cross-linker for ametryn was 1:4.49:22.48. The reversed-phase HPLC-UV was used for the ametryn determination, using an isocratic solvent delivery system (acetonitrile: H(2)O, 60:40), flow-rate of 0.8 mL min(-1) and a UV wavelength of 220 nm. In line with the obtained results, using central composite design (CCD) can increase the precision and accuracy of synthesis and optimization of MIP to ametryn and possibly other similar analogues.


Iterative metal artifact reduction for x-ray computed tomography using unmatched projector/backprojector pairs.
Metal artifact reduction (MAR) is a major problem and a challenging issue in x-ray computed tomography (CT) examinations. Iterative reconstruction from sinograms unaffected by metals shows promising potential in detail recovery. This reconstruction has been the subject of much research in recent years. However, conventional iterative reconstruction methods easily introduce new artifacts around metal implants because of incomplete data reconstruction and inconsistencies in practical data acquisition. Hence, this work aims at developing a method to suppress newly introduced artifacts and improve the image quality around metal implants for the iterative MAR scheme. The proposed method consists of two steps based on the general iterative MAR framework. An uncorrected image is initially reconstructed, and the corresponding metal trace is obtained. The iterative reconstruction method is then used to reconstruct images from the unaffected sinogram. In the reconstruction step of this work, an iterative strategy utilizing unmatched projector/backprojector pairs is used. A ramp filter is introduced into the back-projection procedure to restrain the inconsistency components in low frequencies and generate more reliable images of the regions around metals. Furthermore, a constrained total variation (TV) minimization model is also incorporated to enhance efficiency. The proposed strategy is implemented based on an iterative FBP and an alternating direction minimization (ADM) scheme, respectively. The developed algorithms are referred to as "iFBP-TV" and "TV-FADM," respectively. Two projection-completion-based MAR methods and three iterative MAR methods are performed simultaneously for comparison. The proposed method performs reasonably on both simulation and real CT-scanned datasets. This approach could reduce streak metal artifacts effectively and avoid the mentioned effects in the vicinity of the metals. The improvements are evaluated by inspecting regions of interest and by comparing the root-mean-square errors, normalized mean absolute distance, and universal quality index metrics of the images. Both iFBP-TV and TV-FADM methods outperform other counterparts in all cases. Unlike the conventional iterative methods, the proposed strategy utilizing unmatched projector/backprojector pairs shows excellent performance in detail preservation and prevention of the introduction of new artifacts. Qualitative and quantitative evaluations of experimental results indicate that the developed method outperforms classical MAR algorithms in suppressing streak artifacts and preserving the edge structural information of the object. In particular, structures lying close to metals can be gradually recovered because of the reduction of artifacts caused by inconsistency effects.


The impact of induction duration and the number of high-dose cycles on the long-term survival of women with metastatic breast cancer treated with high-dose chemotherapy with stem cell rescue: an analysis of sequential phase I/II trials from the Dana-Farber/Beth Israel STAMP program.
Although high-dose chemotherapy (HDC) with stem cell rescue for the treatment of women with metastatic breast cancer (MBC) is currently a controversial strategy, we report the long-term outcomes of women undergoing high-dose therapy for MBC over the past 12 years while participating in a sequence of research studies transitioning between a single to a double intensification approach. Univariate and multivariate analyses provide a framework to understand the prognostic factors important for event-free and overall survival. Between May 1988 and April 1998, we enrolled 188 women with MBC into 3 trials of previously reported sequential transplantation strategies. Trial I (long induction/single transplantation) accepted 62 women in partial or complete response to an unspecified induction therapy and treated them with high-dose CTCb (cyclophosphamide, thiotepa, and carboplatin) supported by marrow or peripheral blood progenitor cells (PBPC). Trial II (long induction/double transplantation) accepted 68 women in partial or complete response to an unspecified induction therapy, and mobilized stem cells with 2 cycles of AF (doxorubicin and 5-fluorouracil) with granulocyte colony-stimulating factor (G-CSF). These women then received 1 cycle of high-dose single-agent melphalan followed 3 to 5 weeks later by CTCb, each with marrow or PBPC support. Trial III (short induction/double transplantation) enrolled 58 women prior to chemotherapy treatment for metastatic disease. Induction/mobilization consisted of 2 cycles given 14 days apart of doxorubicin and G-CSF. In contrast to trials I and II, patients with stable disease or better response to induction were eligible to proceed ahead with 2 cycles of HDC, 1 being CTCb and the other being dose escalated paclitaxel together with high-dose melphalan (TxM). These 2 HDC regimens were administered 5 weeks apart. TxM was given first in 32 patients and CTCb was given first in 26 patients. The median follow-up periods for trials I, II, and III were 98, 62, and 39 months from the initiation of induction chemotherapy and 92, 55, and 36 months from last high-dose therapy, respectively. The patient characteristics upon entry into these trials were similar. Important differences were that only those patients achieving a partial response or better to induction therapy were enrolled and analyzed for trials I and II, but all patients were analyzed on an intent-to-treat basis for trial III, including those who did not receive intensification. The median event-free survival (EFS) times from induction chemotherapy were 13, 19, and 27 months for trials I, II, and III, respectively (III versus I + II, P = .0004; III versus I, P = .0005; III versus II, P = .005; II versus I, P = .25). The median overall survival (OS) times from induction chemotherapy were 30, 29, and 57 months for trials I, II, and III, respectively (III versus I + II, P = .002; III versus I, P = .003; III versus II, P = .009; II versus I, P = .47). By multivariate Cox regression, participation in the short induction/double transplantation trial III and having no prior adjuvant chemotherapy remained favorable prognostic factors for both EFS and OS. The presence of visceral disease shortened EFS, and hormone sensitivity was of borderline significance. No substantive differences in the characteristics of the patient populations between the 3 trials appeared to interact with outcomes. In conclusion, we found that single transplantation in responding patients after long induction achieves a small cohort of long-term survivors, similar to the results reported by other transplantation centers. Adding a cycle of single-agent high-dose melphalan in this context delayed median time to relapse but did not affect long-term EFS or OS. The double transplantation approach using CTCb and TxM early in the course of treatment was associated with the best EFS and overall survival and was safe, feasible, and tolerable. Treatment duration was only 14 weeks, and this treatment option eliminated lengthy induction chemotherapy. Although selection biases may have in part contributed to this effect, a randomized comparison of standard therapy versus short induction/double transplantation is warranted.


[Investigation of the effect of oil and flour from wheat germ meal on lipid metabolism of students and teachers of the university].
The results of investigation of alimentary correction of lipid metabolism under the administration of processed products from wheat germ - oil (with the content of policosanol at least 1.5-8.0 mg/100 g, vitamin E - 180-200 mg/100 g, PUFA - 60-65%) and cake flour (with the content of protein - 30-35%, oil with analogue composition -5-7%, digestible carbohydrates - 45-47%, fiber - 18-26%, vitamins B1, B3, B6, B9, E, PP, minerals and trace elements - Zn, Mn, K, Fe, Se, P) are presented. Volunteers among teachers and students of the university aged 16 to 65 years daily consumed wheat germ oil obtained by cold pressing in an amount of 3.5 g, regardless of the meal within 30 days. Then a part of them (30 persons) consumed daily 50 g of oil cake obtained after pressing oil, which provided the intake of the same amount of oil (3.5 g). Lipid metabolism parameters were monitored in experiment participants before receiving the processed products of wheat germ, after germ meal intake and beyond 30 and 60 days after consumption of wheat germ. Data analysis was carried out on three age groups: 16-24, 25-44 and 45- 65 years. All participants of the experiment showed a reduction in total cholesterol level by 6-8%, increasing the concentration of HDL cholesterol by 3-24%, lowering LDL cholesterol concentrations by 4-21%, reduction of triglyceride concentration by 12-24%, a positive correction of atherogenic factor values by for 10-25%. Prolonged action of the investigated foods was established: lipid metabolism parameters in the tested group were better than in the control group after 30 days of intake discontinuation of oil or wheat germ flour, the positive adjustment effect disappeared 60 days after consuming the products. The findings demonstrate a positive effect on the normalization of lipid metabolism when cake flour of wheat germ was administered in daily food ration, similar to the effect of oil intake, which is important for the prevention of cardiovascular diseases and atherosclerosis. Given the significant production of cake flour of wheat germ (up to 90-95% of the raw material) and its not high cost as a secondary biological resource, this product can be recommended to the introduction in the diet of organized groups, including socially vulnerable groups.


Corneal dry-responsive neurons in the spinal trigeminal nucleus respond to innocuous cooling in the rat.
Corneal primary afferent neurons that respond to drying of the ocular surface have been previously characterized and found to respond to innocuous cooling, menthol, and hyperosmotic stimuli. The purpose of the present study was to examine the receptive field properties of second-order neurons in the trigeminal nucleus that respond to drying of the ocular surface. Single-unit electrophysiological recordings were performed in anesthetized rats, and dry-responsive corneal units were isolated in the brain stem at the transition zone between the spinal trigeminal subnucleus caudalis and subnucleus interpolaris. Corneal units were characterized according to their responses to changes in temperature (cooling and heating), hyperosmotic artificial tears, menthol, and low pH. All dry-responsive neurons (n = 18) responded to cooling of the ocular surface. In addition, these neurons responded to hyperosmotic stimuli and menthol application to the cornea. One-half of the neurons were activated by low pH, and these acid-sensitive neurons were also activated by noxious heat. Furthermore, neurons that were activated by low pH had a significantly lower response to cooling and menthol. These results indicate that dry-responsive neurons recorded in the trigeminal nucleus receive input from cold, sensitive primary afferent neurons, with a subset of these neurons receiving input from corneal primary afferent neurons sensitive to acid and noxious heat. It is proposed that acid-insensitive corneal neurons represent a labeled line for lacrimation in response to evaporation of tears from the ocular surface, whereas acid-sensitive neurons are involved in tearing, elicited by damaging or potentially damaging stimuli.


Facilitation of extinction learning for contextual fear memory by PEPA: a potentiator of AMPA receptors.
Contextual fear memory is attenuated by the re-exposure of mice to the context without aversive stimulus. This phenomenon is called extinction. Here, we report that a potentiator of AMPA receptors, 4-[2-(phenylsulfonylamino)ethylthio]-2,6-difluorophenoxyacetamide (PEPA), potently facilitates extinction learning in mice. C57BL/6J mice were exposed to novel context and stimulated by electrical footshock. After 24 h (extinction training) and 72 h (extinction test), the mice were repeatedly exposed to the context without footshock and the duration of their freezing response was measured. The duration of freezing response in the extinction test was consistently shorter than the value in extinction training. Intraperitoneal injection of PEPA 15 min before extinction training remarkably reduced the duration of freezing responses during the extinction training and test, compared with the vehicle-injected control mice. This action of PEPA on extinction was dose-dependent and inhibited by NBQX (1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide), an AMPA receptor antagonist. PEPA had no effect on acquisition and consolidation of fear memory itself. Electrophysiological studies suggested that PEPA activates the neural network much more potently in the medial prefrontal cortex (mPFC) than in the basolateral amygdala and hippocampal CA1 field. Quantitative PCR studies suggested the pronounced expression of PEPA-preferring AMPA receptor subunits (GluR3 and GluR4) and a splice variant (flop) in the mPFC. An intra-mPFC injection of PEPA facilitated the extinction much more potently than an intra-amygdala injection of PEPA did. These results suggest that PEPA facilitates extinction learning through AMPA receptor activation mainly in the mPFC.


Factors Associated with COVID-19 Vaccination Acceptance Among Muslim High School Students in Jakarta Metropolitan Area, Indonesia.
This study aims to identify the factors associated with COVID-19 vaccination uptake and the intention to receive the COVID-19 vaccine among Muslim high school students in Jakarta, Indonesia. A cross-sectional study using an online survey was conducted for high school students. The population in this study were Muslim students grade 11 and 12 at secondary high school living and studying in Jakarta Metropolitan area. A total of 440 samples have been selected using non-probability sampling. In this study, the independent variables were factors associated with vaccination behaviors that were derived from the HBM and TPB theories, while the dependent variables were vaccination uptake and vaccination intention. Factors associated with the dependent variables have been identified using chi-square and Mann-Whitney tests. About 65% respondents had received COVID-19 vaccine and 72% of those who had not received COVID-19 vaccine had the intention to receive the vaccine. Some of the behavioral model variables such as the perceived susceptibility score, perceived severity score, perceived benefits score, perceived barriers score, self-efficacy score, attitude score, and social norms score were significantly associated with COVID-19 vaccine uptake among high school students. Furthermore, all of the behavioral model variables, ie, perceived susceptibility score, perceived severity score, perceived benefits score, perceived barriers score, cues to action score, self-efficacy score, attitude score, social norms score, and perceived behavioral control score were significantly associated with an intention of being vaccinated. The vaccination for students can be set in more affordable locationsfor example, in schools. In addition, efforts to increase student knowledge regarding the effectiveness and safety of vaccines and the dangers of COVID-19 should be sustained.


A comparative evaluation of the tensile strength of silver soldered joints of stainless steel and cobalt chromium orthodontic wires with band material--an in vitro study.
The present study was conducted to compare and evaluate the tensile strength of silver soldered joints of stainless steel and cobalt-chromium orthodontic wires with band material. An attempt was made to observe the effect of joint site preparation by incorporation of tack welding and increasing metal to metal surface contact area by flattening an end of the wire prior to soldering along with the regularly used round wires without tack welding. A total of 180 wire specimens were soldered to 180 band specimens. Fifteen samples according to joint site preparation were included for each of the wire groups i.e. Gloria (S.S.), Remanium (S.S.) and Remaloy (Co-Cr) wires of 0.036" in diameter. The findings of the study were suggestive that all three wires may be used for preparing silver soldered joints irrespective of the quality of the wire. However, when subjecting the wire to joint site preparation, Gloria (S.S.) wire showed less tensile strength as compared to Remanium and Remaloy.


Power and efficiency scaling of diode pumped Cr:LiSAF lasers: 770-1110 nm tuning range and frequency doubling to 387-463 nm.
We report significant average power and efficiency scaling of diode-pumped Cr:LiSAF lasers in continuous-wave (cw), cw frequency-doubled, and mode-locked regimes. Four single-emitter broad-area laser diodes around 660 nm were used as the pump source, which provided a total pump power of 7.2 W. To minimize thermal effects, a 20 mm long Cr:LiSAF sample with a relatively low Cr-concentration (0.8%) was used as the gain medium. In cw laser experiments, 2.4 W of output power, a slope efficiency of 50%, and a tuning range covering the 770-1110 nm region were achieved. Intracavity frequency doubling with beta-barium borate (BBO) crystals generated up to 1160 mW of blue power and a record tuning range in the 387-463 nm region. When mode locked with a saturable absorber mirror, the laser produced 195 fs pulses with 580 mW of average power around 820 nm at a 100.3 MHz repetition rate. The optical-to-optical conversion efficiency of the system was 33% in cw, 16% in cw frequency-doubled, and 8% in cw mode-locked regimes.


Mediastinal Lymphadenopathy in Patients with Systemic Sclerosis.
There are few studies regarding the characteristics of mediastinal lymphadenopathy (MN) in patients with systemic sclerosis (SSc). Understanding its features could help radiologists interpret lung imaging more confidently. To determine the prevalence and characteristics of MLN in patients with SSc and factors associated with MLN. A retrospective review of medical records and high resolution computed tomography (HRCT) of the lungs of all patients with SSc at Srinagarind Hospital, Khon Kaen University, Thailand between 2009 and 2011 was done. Univariate and multivariate logistic regressions were used to analyze the outcomes. Sixty patients were eligible for the present study; the majority of them was women (71.7%) and had diffuse SSc (71.7%). The prevalence of MLN was 56.7% (36 in 60 cases). The distribution of MLN was mainly found in two or more locations (47.1%) and had isodensity on imaging (61.3%). The median size of nodes was 1.2 cm (inter-quartile range 1, 1.4 cm). Only the pulmonary fibrosis score was significantly associated with MLN with the adjusted odds ratio of 1.2 (95% confidence interval 1.1, 1.4, p = 0.03). There was no association between MLN with other factors. MLN was prevalent in patients with SSc. The pulmonary fibrosis score was an independent factor associated with MLN.


System-size resonance in a binary attractor neural network.
System size resonance (SSR) is a phenomenon in which the response of a system is optimal for a certain finite size, but poorer as the size goes to zero or infinity. In order to show SSR effects in binary attractor neural networks, we study the response of a network, in the ferromagnetic phase, to an external, time-dependent stimulus. Under the presence of such a stimulus, the network shows SSR, as is demonstrated by the measure of the signal amplification both analytically and by simulation.


NU-9 improves health of hSOD1G93A mouse upper motor neurons in vitro, especially in combination with riluzole or edaravone.
Even though amyotrophic lateral sclerosis (ALS) is a disease of the upper and lower motor neurons, to date none of the compounds in clinical trials have been tested for improving the health of diseased upper motor neurons (UMNs). There is an urgent need to develop preclinical assays that include UMN health as a readout. Since ALS is a complex disease, combinatorial treatment strategies will be required to address the mechanisms perturbed in patients. Here, we describe a novel in vitro platform that takes advantage of an UMN reporter line in which UMNs are genetically labeled with fluorescence and have misfolded SOD1 toxicity. We report that NU-9, an analog of the cyclohexane-1,3-dione family of compounds, improves the health of UMNs with misfolded SOD1 toxicity more effectively than riluzole or edaravone, -the only two FDA-approved ALS drugs to date-. Interestingly, when NU-9 is applied in combination with riluzole or edaravone, there is an additive effect on UMN health, as they extend longer axons and display enhanced branching and arborization, two important characteristics of healthy UMNs in vitro.


An Observational Study on the Utility of Lab Parameters in Evaluating the Severity of Patients in South India with Covid-19.
Laboratory testing has been extremely helpful in determining the severity and determining the course of treatment for COVID-19 patients. Our aim has been to look for variables of patient's clinical and laboratory profile for two weeks and to observe their significance. Observational, Cross-sectional study. Data from the clinic and laboratory were compiled on Google form after informed consent from the patient. Statistical analysis was done using the Mann-Whitney U and unpaired t test. Population statistics included 202 patients (1st week) and 161 patients (2nd week), with the mean age of 61 ± 18 years. Most patients fell under the mild category (SPO2 >94%). High body mass index (n = 119) and hypertensive (n = 98) were the most common comorbidities observed. Diabetes, cardiovascular and respiratory diseases are the other comorbidities studied in this study. Hypoalbuminemia (n = 194) is the most deranged laboratory parameter in mild category, followed by lymphopenia (n = 109). In severe category also, hypoalbuminemia (n = 13) was deranged more. Other laboratory parameters included are CRP, D-Dimer, neutrophil and lymphocyte count. This study showed that albumin is a good predictor for estimating the severity of COVID-19 patients especially in the first week of their admission.


Probing community nurses' professional basis: a situational case study in diabetic foot ulcer treatment.
Complicated and long-lasting wound care of diabetic foot ulcers are moving from specialists in wound care at hospitals towards community nurses without specialist diabetic foot ulcer wound care knowledge. The aim of the study is to elucidate community nurses' professional basis for treating diabetic foot ulcers. A situational case study design was adopted in an archetypical Danish community nursing setting. Experience is a crucial component in the community nurses' professional basis for treating diabetic foot ulcers. Peer-to-peer training is the prevailing way to learn about diabetic foot ulcer, however, this contributes to the risk of low evidence-based practice. Finally, a frequent behaviour among the community nurses is to consult colleagues before treating the diabetic foot ulcers.


Disorder effects in focused-ion-beam-deposited Pt contacts on GaN nanowires.
The current-bias (I-V) characteristics at various temperatures, T, of focused-ion-beam (FIB)-deposited Pt contacts on GaN nanowires evolves from low-resistance ohmic (linear I-V) to rectifying as the diameter increases, and both exhibit strongly nonmetallic T-dependence. The small-diameter (66 nm) T-dependent resistance is explained by two-dimensional variable range hopping with a small characteristic energy, ensuring low resistance at 300 K. For large diameters (184 nm), back-to-back Schottky barriers explain the nonlinear I-V at all T values and permit an estimate of doping concentration from the bias-dependent barrier height. Both behaviors can be understood by accounting for the role of FIB-induced amorphization of GaN underneath the contact, as confirmed by cross-sectional transmission electron microscopy.


Selecting and optimising patients for total knee arthroplasty.
The minimum requirements for total knee arthroplasty (TKA) are significant, prolonged symptoms with supporting clinical and radiological signs. Despite interest in screening tools, there is limited evidence for a specific symptom threshold that justifies surgery. Non-operative treatments including medications, exercise and weight loss are unlikely to reverse radiographic changes, but they may improve symptoms and delay the need for surgery. Many patient factors such as mental health and obesity affect both the level of symptomatic improvement after surgery and risks of surgery, but none have been identified as contraindications for the procedure as significant health gains can still be achieved. Although age and sex are associated with patient-reported outcomes and risk of revision, these factors cannot be used to restrict access to TKA, and age cut-offs are not recommended. Evidence regarding pre-operative optimisation of patients to improve post-operative TKA outcomes is limited by the few interventional trials available, particularly in the areas of patient expectation, diabetes, obesity and vascular disease. There is good evidence from randomised controlled trials that pre-operative rehabilitation primarily focusing on exercises for the joint or limb has minimal effect on post-operative TKA outcomes, and there is some evidence from randomised controlled trials that an intensive smoking cessation program before surgery may improve post-operative outcomes. Detailed international guidelines exist on the optimisation of the cardiorespiratory status of surgical patients, and these should be followed for TKA surgery.


Low-energy linear structures in dense oxygen: implications for the epsilon phase.
Using density functional theory implemented within the generalized gradient approximation, a new nonmagnetic insulating ground state of solid oxygen is proposed and found to be energetically favored at pressures corresponding to the epsilon phase. The newly predicted static ground state is composed of linear herringbone-type chains of O2 molecules and has Cmcm symmetry (with an alternative monoclinic cell). Importantly, this phase supports IR-active zone-center phonons, and their computed frequencies are found to be in broad agreement with recent infrared absorption experiments.


Low neutrophil-to-lymphocyte ratio predicts overall survival benefit in advanced NSCLC patients with low PD-L1 expression and receiving chemoimmunotherapy.
Although combination therapy including chemotherapy and immune checkpoint inhibitors (ICIs) improves overall survival (OS) of patients with non-small-cell lung cancer (NSCLC), there is a higher incidence of adverse events and treatment discontinuation. Since programmed death-ligand 1 (PD-L1) could not serve as a predictive biomarker, we investigated the neutrophil-to-lymphocyte ratio (NLR) as a predictive biomarker. In our previous research, we demonstrated that a low NLR could predict survival benefits when patients with high PD-L1 expression (> 50%) received chemoimmunotherapy as opposed to immunotherapy alone. In this current study, our objective is to evaluate this predictive capacity in patients with low PD-L1 expression (< 50%). A total of 142 patients were enrolled, 28 receiving combination therapy and 114 receiving chemotherapy alone. Progression-free survival (PFS) and OS were estimated using the Kaplan-Meier method and compared using the log-rank test. Patients who received combination therapy had significantly better PFS and OS than those who received monotherapy. In the subgroup of patients with low NLR, those who received combination therapy exhibited extended PFS and OS with clinical significance, which was also confirmed by multivariate Cox regression analysis. Our study demonstrates the potential use of NLR as a biomarker for predicting survival benefits when receiving combination therapy with chemotherapy and ICIs in patients with advanced NSCLC and low PD-L1 expression.


KCa3.1 Inhibition of Macrophages Suppresses Inflammatory Response Leading to Endothelial Damage in a Cell Model of Kawasaki Disease.
Macrophages-mediated inflammation is linked with endothelial damage of Kawasaki disease (KD). KCa3.1, a calcium-activated potassium channel, modulates inflammation of macrophages. However, little is known about the role of KCa3.1 in inflammation by macrophages involved in KD. Hence, this study is aimed to explore the potential role of KCa3.1 in regulating inflammatory response by macrophages and subsequent vascular injury in an in vitro model of KD. RAW264.7 cells were stimulated with Lactobacillus casei cell wall extract (LCWE) with or without TRAM-34 or PDTC or AG490. Subsequently, mouse coronary artery endothelial cells (MCAECs) were incubated with RAW264.7 cells-conditioned medium to mimic local inflammatory lesions in KD. CCKi8 assay was used to evaluate cell viability. The mRNA levels of inflammatory mediators were detected by qRT-PCR. Expressions of KCa3.1, MCAECs injury-associated molecules, proteins involved in signal pathways of nuclear factor-κB (NF-κB), signal transducers and activators of transcription (STAT) 3 and p38 were evaluated by Western blot. Our study showed that LCWE increased KCa3.1 protein level in RAW264.7 macrophages and KCa3.1 inhibition by TRAM-34 notably suppressed the expression of pro-inflammatory molecules in LCWE-treated macrophages via blocking the activation of NF-κB and STAT3 pathways. Besides, the inflammation and damage of MCAECs were attenuated in the TRAM-34-treated group compared with the KD model group. This vascular protective role was dependent on the down-regulation of NF-κB and STAT3 signal pathways, which was confirmed by using inhibitors of NF-κB and STAT3. This study demonstrates that KCa3.1 blockade of macrophages suppresses inflammatory reaction leading to mouse coronary artery endothelial cell injury in a cell model of KD by hampering the activation of NF-κB and STAT3 signaling pathway. These findings imply that KCa3.1 may be a potential therapeutic target for KD.


Manganese-Catalyzed Ring-Opening Coupling Reactions of Cyclopropanols with Enones.
A manganese-catalyzed ring-opening coupling reaction of cyclopropanols with enones for the facile and efficient preparation of 1,6-diketones is described. A wide array of synthetically important 1,6-diketones bearing manifold functional groups are obtained with up to 93% yield. These reactions feature broad substrate scopes, environmentally benign conditions, inexpensive catalyst, and operational simplicity.


Effect of Early and Prophylactic Nonsteroidal Anti-Inflammatory Drugs on Flare Duration in Pediatric Acute-Onset Neuropsychiatric Syndrome: An Observational Study of Patients Followed by an Academic Community-Based Pediatric Acute-Onset Neuropsychiatric Syndrome Clinic.
Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) is characterized by the sudden onset of severe obsessive-compulsive symptoms and/or eating restriction along with at least two coinciding neuropsychiatric symptoms. When associated with group A Streptococcus, the syndrome is labeled Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal infections (PANDAS). An abnormal immune response to infection and subsequent neuroinflammation is postulated to play an etiologic role. We evaluated the impact of nonsteroidal anti-inflammatory drug (NSAID) treatment on flare duration in PANS/PANDAS. Patient inclusion criteria: Patients were included if they had at least one neuropsychiatric deterioration ("flare") that met strict PANS/PANDAS research criteria and for which flare duration could be assessed. Flare inclusion criteria: Any flare that started before October 15, 2016 was included and followed until the flare resolved or until the end of our data collection (November 1, 2016). Flare exclusion criteria: Flares were excluded if they were incompletely resolved, treated with aggressive immunomodulation, or treated with NSAIDs late (>30 days of flare onset). Ninety-five patients met study inclusion criteria and collectively experienced 390 flares that met flare criteria. Data were analyzed using multilevel linear models, adjusting for demographics, disease, and treatment covariates. NSAID use was associated with a significantly shorter flare duration. Flares not treated with NSAIDs had a mean duration of approximately 12.2 weeks (95% CI: 9.3-15.1). Flares that occurred while the child was on NSAID maintenance therapy were approximately 4 weeks shorter than flares not managed with NSAIDs (95% CI: 1.85-6.24; p < 0.0001). Flares treated with NSAIDs within 30 days of flare onset were approximately 2.6 weeks shorter than flares not managed with NSAIDs (95% CI: 0.43-4.68; p = 0.02). Flares treated prophylactically and those treated early with NSAIDs did not differ in duration (p = 0.26). Among the flares that received NSAID treatment within the first 30 days, earlier intervention was modestly associated with shorter flare durations (i.e., for each day that NSAID treatment was delayed, flare duration increased by 0.18 weeks; 95% CI: 0.03-0.33; p = 0.02), though it was not statistically significant after controlling for covariates (p = 0.06). NSAIDs given prophylactically or within 30 days of flare onset may shorten neuropsychiatric symptom duration in patients with new-onset and relapsing/remitting PANS and PANDAS. A randomized placebo-control clinical trial of NSAIDs in PANS is warranted to formally assess treatment efficacy.


[Relationship of psychiatric comorbidity and treatment of panic disorder and agoraphobia].
Besides numerous studies that examined various aspects of comorbidity in patients with panic disorder and agoraphobia and numerous studies that examined efficacy of different treatment modalities in these patients, there was no study that examined relationship of overall psychiatric comorbidity and treatment of patients with panic disorder and agoraphobia. The objective of the study was to establish the effect of psychiatric comorbidity on treatment efficiency of patients with panic disorder and agoraphobia. The sample of the study consisted of 119 patients with primary diagnosis of panic disorder and agoraphobia. The therapy of patients was based on the use of individual integrative model of treatment, which incorporated psycho-pharmaceuticals (benzodiazepines and antidepressants) and cognitive-behavior therapy. Symptom severity was estimated by Panic and Agoraphobia Scale before and after the completion of treatment. Patients with comorbidity and patients without any comorbidity were compared by MANOVA and ANOVA with repeated measures. The results of the study showed that 91% of patients met diagnostic criteria of comorbid psychiatric disorder and these patients had more severe clinical picture than patients without any comorbid disorder before the treatment. The results also showed that, after the completion of treatment, there was a significant reduction of all analyzed symptoms, that the effects of treatment were significantly better in patients with psychiatric comorbidity and that comorbid psychiatric disorders had no negative effect on the main goals of the treatment. Based on these results, it may be concluded that: in patients with panic disorder and agoraphobia and comorbid psychiatric disorders, the pharmacotherapy must be based on simultaneous use of antidepressants and benzodiazepines, while standard cognitive-behavior therapy of patients with panic disorder and agoraphobia must be modified in case of the existing comorbid psychiatric disorders.


Nonresponse bias to mail survey questionnaires within a professional population.
Mail survey questionnaires are often used in dental research. In most instances, results depend on a single mailing and an incomplete return rate. The possible bias resulting from excluding nonresponders in tabuling data from mail survey questionnaires in a dentist population was investigated. Two different questionnaires, one soliciting attitudes, the other knowledge, were sent to randomly selected dentists. The differences between the responders and the nonresponders were analyzed with respect to the dentists' demographic data, attitudes, and knowledge. It was concluded that: (1) subject matter does affect dentist response rates to mailed survey questionnaires, (2) there are no differences in demographic data between dentist responders and nonresponders, and (3) nonresponse bias does not affect the results of dental surveys on a typical dentist response rate.


Evaluation of a 2% chlorhexidine gluconate in 70% isopropyl alcohol skin disinfectant.
The efficacy of a new skin disinfectant, 2% (w/v) chlorhexidine gluconate (CHG) in 70% (v/v) isopropyl alcohol (IPA) (ChloraPrep), was compared with five commonly used skin disinfectants against Staphylococcus epidermidis RP62A in the presence or absence of protein, utilizing quantitative time-kill suspension and carrier tests. All six disinfectants [70% (v/v) IPA, 0.5% (w/v) aqueous CHG, 2% (w/v) aqueous CHG, 0.5% (w/v) CHG in 70% (v/v) IPA and 10% (w/v) aqueous povidone iodine (PI)] achieved a log(10) reduction factor of 5, in colony-forming units/mL, in a suspension test (exposure time 30s) in the presence and absence of 10% human serum. Subsequent challenges of S. epidermidis RP62A in a biofilm (with and without human serum) demonstrated reduced bactericidal activity. Overall, the most effective skin disinfectants tested against S. epidermidis RP62A were 2% (w/v) CHG in 70% IPA and 10% (w/v) PI. These results suggest that enhanced skin antisepsis may be achieved with 2% (w/v) CHG in 70% (v/v) IPA compared with the three commonly used CHG preparations [0.5% (w/v) aqueous CHG, 2% (w/v) aqueous CHG and 0.5% (w/v) CHG in 70% (v/v) IPA].


Stress Marks on the Genome: Use or Lose?
Oxidative stress and the resulting damage to DNA are inevitable consequence of endogenous physiological processes further amplified by cellular responses to environmental exposures. If left unrepaired, oxidative DNA lesions can block essential processes such as transcription and replication or can induce mutations. Emerging data also indicate that oxidative base modifications such as 8-oxoG in gene promoters may serve as epigenetic marks, and/or provide a platform for coordination of the initial steps of DNA repair and the assembly of the transcriptional machinery to launch adequate gene expression alterations. Here, we briefly review the current understanding of oxidative lesions in genome stability maintenance and regulation of basal and inducible transcription.