Association of total marine fatty acids, eicosapentaenoic and docosahexaenoic acids, with aortic stiffness in Koreans, whites, and Japanese Americans.
Few previous studies have reported the association of aortic stiffness with marine n-3 fatty acids (Fas) in the general population. The aim of this study was to determine the combined and independent associations of 2 major marine n-3 FAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), with aortic stiffness evaluated using carotid-femoral pulse wave velocity (cfPWV) in Korean, white, and Japanese American men. A population-based sample of 851 middle-aged men (299 Koreans, 266 whites, and 286 Japanese Americans) was examined for cfPWV during 2002-2006. Serum FAs, including EPA and DHA, were measured as a percentage of total FAs using gas chromatography. Multiple regression analysis was used to examine the association of EPA and DHA with cfPWV after adjusting for blood pressure and other confounders. Mean EPA and DHA levels were 1.9 (SD = 1.0) and 4.8 (SD = 1.4) for Koreans, 0.8 (SD = 0.6) and 2.4 (SD = 1.2) for whites, and 1.0 (SD = 1.0) and 3.2 (SD = 1.4) for Japanese Americans. Both EPA and DHA were significantly higher in Koreans than in the other 2 groups (P < 0.01). Multiple regression analyses in Koreans showed that cfPWV had a significant inverse association with total marine n-3 FAs and with EPA alone after adjusting for blood pressure and other potential confounders. In contrast, there was no significant association of cfPWV with DHA. Whites and Japanese Americans did not show any significant associations of cfPWV with total marine n-3 FAs, EPA, or DHA. High levels of EPA observed in Koreans have an inverse association with aortic stiffness.


A case of decompression sickness at 2,437 meters (8,000 feet).
Among aviators, decompression sickness is a condition that occurs almost exclusively at altitudes above 6,098 m (20,000 ft). Several reports have been published describing the development of decompression sickness after altitude exposures of 3,049 to 4,878 m (10,000-16,000 ft). In most of these cases, the affected individual had a previous history of pain in the involved area due to prior trauma or surgery, or had other risk factors for decompression sickness, such as obesity. Few of these reports have confirmed the presence of decompression sickness by a test of pressure. A case is reported here of multiple joint pains developing after a rapid decompression at 2,439 m (8,000 ft), which improved during descent and rapidly resolved with recompression therapy. There was no prior history of joint pain, trauma, or diving. A brief discussion of decompression sickness is included.


Geometric calibration of lens and filter distortions for multispectral filter-wheel cameras.
High-fidelity color image acquisition with a multispectral camera utilizes optical filters to separate the visible electromagnetic spectrum into several passbands. This is often realized with a computer-controlled filter wheel, where each position is equipped with an optical bandpass filter. For each filter wheel position, a grayscale image is acquired and the passbands are finally combined to a multispectral image. However, the different optical properties and non-coplanar alignment of the filters cause image aberrations since the optical path is slightly different for each filter wheel position. As in a normal camera system, the lens causes additional wavelength-dependent image distortions called chromatic aberrations. When transforming the multispectral image with these aberrations into an RGB image, color fringes appear, and the image exhibits a pincushion or barrel distortion. In this paper, we address both the distortions caused by the lens and by the filters. Based on a physical model of the bandpass filters, we show that the aberrations caused by the filters can be modeled by displaced image planes. The lens distortions are modeled by an extended pinhole camera model, which results in a remaining mean calibration error of only 0.07 pixels. Using an absolute calibration target, we then geometrically calibrate each passband and compensate for both lens and filter distortions simultaneously. We show that both types of aberrations can be compensated and present detailed results on the remaining calibration errors.


Clinical features related to statin-associated muscle symptoms.
Statins reduce cardiovascular disease risk and are generally well tolerated, yet up to 0.5% of statin-treated patients develop incapacitating muscle symptoms including rhabdomyolysis. Our objective was to identify clinical factors related to statin-associated muscle symptoms (SAMS). Clinical and laboratory characteristics were evaluated in 748 statin-treated Caucasians (634 with SAMS and 114 statin-tolerant controls). Information was collected on statin type, concomitant drug therapies, muscle symptom history, comorbidities, and family history. Logistic regression was used to identify associations. Individuals with SAMS were 3.6 times (odds ratio [OR] 3.60, 95% confidence interval [CI] 2.08-6.22) more likely than statin-tolerant controls to have a family history of heart disease. Additional associations included obesity (OR 3.08, 95% CI 1.18, 8.05), hypertension (OR 2.24, 95% CI 1.33, 3.77), smoking (OR 2.08, 95% CI 1.16, 3.74), and statin type. Careful medical monitoring of statin-treated patients with the associated coexisting conditions may ultimately reduce muscle symptoms and lead to improved compliance. Muscle Nerve 59:537-537, 2019.


Regulation of aryl hydrocarbon receptor interacting protein (AIP) protein expression by MiR-34a in sporadic somatotropinomas.
Patients with germline AIP mutations or low AIP protein expression have large, invasive somatotroph adenomas and poor response to somatostatin analogues (SSA). To study the mechanism of low AIP protein expression 31 sporadic somatotropinomas with low (n = 13) or high (n = 18) AIP protein expression were analyzed for expression of AIP messenger RNA (mRNA) and 11 microRNAs (miRNAs) predicted to bind the 3'UTR of AIP. Luciferase reporter assays of wild-type and deletion constructs of AIP-3'UTR were used to study the effect of the selected miRNAs in GH3 cells. Endogenous AIP protein and mRNA levels were measured after miRNA over- and underexpression in HEK293 and GH3 cells. No significant difference was observed in AIP mRNA expression between tumors with low or high AIP protein expression suggesting post-transcriptional regulation. miR-34a was highly expressed in low AIP protein samples compared high AIP protein adenomas and miR-34a levels were inversely correlated with response to SSA therapy. miR-34a inhibited the luciferase-AIP-3'UTR construct, suggesting that miR-34a binds to AIP-3'UTR. Deletion mutants of the 3 different predicted binding sites in AIP-3'UTR identified the c.*6-30 site to be involved in miR-34a's activity. miR-34a overexpression in HEK293 and GH3 cells resulted in inhibition of endogenous AIP protein expression. Low AIP protein expression is associated with high miR-34a expression. miR-34a can down-regulate AIP-protein but not RNA expression in vitro. miR-34a is a negative regulator of AIP-protein expression and could be responsible for the low AIP expression observed in somatotropinomas with an invasive phenotype and resistance to SSA.


Look at what I can do: Object affordances guide visual attention while speakers describe potential actions.
As we act on the world around us, our eyes seek out objects we plan to interact with. A growing body of evidence suggests that overt visual attention selects objects in the environment that could be interacted with, even when the task precludes physical interaction. In previous work, objects that afford grasping interactions influenced attention when static scenes depicted reachable spaces, and attention was otherwise better explained by general informativeness. Because grasping is but one of many object interactions, previous work may have downplayed the influence of object affordances on attention. The current study investigated the relationship between overt visual attention and object affordances versus broadly construed semantic information in scenes as speakers describe or memorize scenes. In addition to meaning and grasp maps-which capture informativeness and grasping object affordances in scenes, respectively-we introduce interact maps, which capture affordances more broadly. In a mixed-effects analysis of 5 eyetracking experiments, we found that meaning predicted fixated locations in a general description task and during scene memorization. Grasp maps marginally predicted fixated locations during action description for scenes that depicted reachable spaces only. Interact maps predicted fixated regions in description experiments alone. Our findings suggest observers allocate attention to scene regions that could be readily interacted with when talking about the scene, while general informativeness preferentially guides attention when the task does not encourage careful consideration of objects in the scene. The current study suggests that the influence of object affordances on visual attention in scenes is mediated by task demands.


Pediatric cataracts: clinical aspects, frequency of strabismus and chronological, etiological, and morphological features.
This study aimed to evaluate the frequency of strabismus and chronological, etiological, and morphological features in patients with pediatric cataracts. Medical records of pediatric patients were evaluated at the Congenital Cataract Section, Department of Ophthalmology, Federal University of São Paulo, from 2001 to 2011. Patients with congenital cataract or developmental cataract were included. The patients with traumatic cataract, cataract secondary to uveitis, radiation or drugs, aphakic or pseudophakic patients who underwent surgery in another hospital, patients with glaucoma, non-lenticular leukocorias (retinoblastoma, retinopathy of prematurity, prelenticular leukocorias), and lens subluxation were excluded from the study. The following outcomes were evaluated: frequency of chronological, etiological, and morphological features, laterality, and occurrence of associated strabismus. A total of 207 patients were included. One hundred and seventeen patients (56.5%) had congenital cataract and 90 patients (43.5%) had developmental cataract. One hundred and nine patients (52.6%) had unilateral cataract. In terms of morphology, 72 children (33.8%) had zonular cataract and 66 (31.9%) had total cataract. Idiopathic cataract affected 150 patients (72.5%). There were 108 patients (52.2%) with strabismus, mainly secondary esotropia. Idiopathic etiology was the most frequent cause in this group of patients. Zonular cataract was the main morphological type of cataract in the study. Unilateral cataract occurred more frequently in patients with persistent fetal vasculature (PFV). Strabismus presented in 52% of the patients. The current analysis may help establish an earlier and more accurate diagnosis of pediatric cataracts.


The effects of magnesium hydroxide on the absorption and efficacy of two glibenclamide preparations.
1. The effect of magnesium hydroxide on the absorption and efficacy of two glibenclamide preparations was investigated in healthy volunteers in two separate studies, using a randomized cross-over design with two phases. 2. A single dose of magnesium hydroxide (850 mg) or water only (150 ml) was given immediately after the ingestion of a micronised (1.75 mg, seven subjects) or a non-micronised (2.5 mg, six subjects) preparation of glibenclamide. Plasma concentrations of glibenclamide, insulin and glucose were measured. 3. Magnesium hydroxide accelerated (P less than 0.05) the absorption of glibenclamide from the micronised preparation to a small extent but the extent of absorption and the insulin and glucose responses were unaltered. 4. Coadministration of magnesium hydroxide with the non-micronised glibenclamide preparation increased the area under the plasma glibenclamide concentration-time curve from 0 to 3 h, five-fold (P less than 0.05), the total area three-fold (P less than 0.05) and the peak drug concentration three-fold (P less than 0.05). The incremental insulin area from 0 to 3 h was increased 35-fold (P less than 0.05) and the maximum insulin response 10-fold (P less than 0.05) by magnesium hydroxide. 5. Concomitant ingestion of magnesium hydroxide and non-micronised glibenclamide may greatly enhance the absorption and efficacy of glibenclamide. The absorption of micronised glibenclamide appears to be only slightly influenced by magnesium hydroxide.


Telomerase and cell proliferation in mouse skin papillomas.
The progression of chemically induced mouse skin papillomas is paralleled by an increase in telomerase activity. In this study, we compared telomerase activity and rate of cell proliferation in papillomas obtained early versus late in papilloma progression. Eighteen early papillomas (after 15 wk of promotion) showed no evidence of telomerase activity, and their average cell proliferation index was 26.6% +/- 6.3. On the other hand, most of the papillomas harvested after 25 wk of promotion showed high levels of telomerase activity, but their average cell proliferation index (30.8% +/- 6.2) was not different from that of the early lesions. We concluded that there appears to be no association between the level of telomerase activity observed in mouse skin papillomas and the rate of cell proliferation of each individual tumor. Telomerase expression may indicate the existence of more abundant tumor subpopulations in advanced papillomas with proliferative potential for autonomous growth.


Adaption of luting cement to enamel, dentin and restorative material.
Thirty-two teeth with artificial crowns cemented with four different cements were sectioned and the cementing interfaces were studied by means of a replica technique. Scanning electronic microscopic examination of the replicas demonstrated that slits occurred in all specimens either at the cement/tooth interface, the cement/alloy interface or both. Differences between the various cements in width and length of the slits could not be assessed by this method, but marked variations in the localization of the slits were noted. A composite resin cement showed slits only at the cement/tooth interface. A zinc phosphate and an EBA cement showed slits at both interfaces whereas a polycarboxylate cement was the only cement which exhibited good adaption to enamel and dentin, leaving gaps at the cement/alloy interface.


Virologic response following combined ledipasvir and sofosbuvir administration in patients with HCV genotype 1 and HIV co-infection.
There is an unmet need for interferon- and ribavirin-free treatment for chronic hepatitis C virus (HCV) infection in patients co-infected with human immunodeficiency virus (HIV). To evaluate the rates of sustained virologic response (SVR) and adverse events in previously untreated patients with HCV genotype 1 and HIV co-infection following a 12-week treatment of the fixed-dose combination of ledipasvir and sofosbuvir. Open-label, single-center, phase 2b pilot study of previously untreated, noncirrhotic patients with HCV genotype 1 and HIV co-infection conducted at the Clinical Research Center of the National Institutes of Health, Bethesda, Maryland, from June 2013 to September 2014. Patients included those receiving antiretroviral therapy with HIV RNA values of 50 copies/mL or fewer and a CD4 T-lymphocyte count of 100 cells/mL or greater or patients with untreated HIV infection with a CD4 T-lymphocyte count of 500 cells/mL or greater. Serial measurements of safety parameters, virologic and host immune correlates, and adherence were performed. Fifty patients with HCV genotype 1 never before treated for HCV were prescribed a fixed-dose combination of ledipasvir (90 mg) and sofosbuvir (400 mg) once daily for 12 weeks. The primary study outcome was the proportion of patients with sustained viral response (plasma HCV RNA level <12 IU/mL) 12 weeks after end of treatment. Forty-nine of 50 participants (98% [95% CI, 89% to 100%]) achieved SVR 12 weeks after end of treatment, whereas 1 patient experienced relapse at week 4 following treatment. In the patient with relapse, deep sequencing revealed a resistance associated mutation in the NS5A region conferring resistance to NS5A inhibitors, such as ledipasvir. The most common adverse events were nasal congestion (16% of patients) and myalgia (14%). There were no discontinuations or serious adverse events attributable to study drug. In this open-label, uncontrolled, pilot study enrolling patients co-infected with HCV genotype 1 and HIV, administration of an oral combination of ledipasvir and sofosbuvir for 12 weeks was associated with high rates of SVR after treatment completion. Larger studies that also include patients with cirrhosis and lower CD4 T-cell counts are required to understand if the results of this study generalize to all patients co-infected with HCV and HIV. clinicaltrials.gov Identifier:NCT01878799.


The binding of peroxidase-labelled lectins to human breast epithelium. IV--The reactivity of breast carcinomas to peanut, soy bean and Dolichos biflorus agglutinins.
The binding of the lectins from peanut, soy bean and Dolichos biflorus (specific for galactose and/or N-acetyl-D-galactosamine), to human breast carcinomas has been investigated. In contrast to the consistent pattern found in normal breast the reactivity of carcinomas to peanut lectin is varied, the most striking differences being prominent binding without desialation in some tumours and virtual lack of reactivity in others. There tends to be a greater degree of binding of soy bean agglutinin to carcinomas than normal although this is not absolute, and the reverse applies to Dolichos biflorus agglutinin. Comparison of the binding of the three lectins has revealed a complex heterogeneity of the carbohydrate chains within individual tumours and between different carcinomas. A significant relationship between peanut lectin binding, with the use of neuraminidase, and tumour differentiation as been found, and to a lesser extent with soy bean agglutinin when desialation is performed. However, the pattern of reactivity of the carcinomas with these three lectins does not appear to be related to local lymph node metastasis.


Imaging with radiolabelled anti-membrane type 1 matrix metalloproteinase (MT1-MMP) antibody: potentials for characterizing atherosclerotic plaques.
Membrane type 1 matrix metalloproteinase (MT1-MMP) activates pro-MMP-2 and pro-MMP-13 to their active forms and plays important roles in the destabilization of atherosclerotic plaques. This study sought to determine the usefulness of (99m)Tc-labelled monoclonal antibody (mAb), recognizing MT1-MMP, for imaging atherosclerosis in a rabbit model (WHHLMI rabbits). Anti-MT1-MMP monoclonal IgG(3) and negative control IgG(3) were radiolabelled with (99m)Tc after derivatization with 6-hydrazinonicotinic acid (HYNIC) to yield (99m)Tc-MT1-MMP mAb and (99m)Tc-IgG(3), respectively. WHHLMI and control rabbits were injected with these radio-probes. The aorta was removed and radioactivity was measured at 24 h after the injection. Autoradiography and histological studies were performed. (99m)Tc-MT1-MMP mAb accumulation in WHHLMI rabbit aortas was 5.4-fold higher than that of control rabbits. Regional (99m)Tc-MT1-MMP mAb accumulation was positively correlated with MT1-MMP expression (r = 0.59, p < 0.0001), while (99m)Tc-IgG(3) accumulation was independent of MT1-MMP expression (r = 0.03, p = NS). The highest (99m)Tc-MT1-MMP mAb accumulation was found in atheromatous lesions (4.8 ± 1.9, %ID×BW/mm(2) × 10(2)), followed in decreasing order by fibroatheromatous (1.8 ± 1.3), collagen-rich (1.6 ± 1.0) and neointimal lesions (1.5 ± 1.5). In contrast, (99m)Tc-IgG(3) accumulation was almost independent of the histological grade of lesions. Higher (99m)Tc-MT1-MMP mAb accumulation in grade IV atheroma was shown in comparison with neointimal lesions or other more stable lesions. Nuclear imaging with (99m)Tc-MT1-MMP mAb, in combination with CT and MRI, could provide new diagnostic imaging capabilities for detecting vulnerable plaques, although further investigations to improve target to blood ratios are strongly required.


TRPV3 is a temperature-sensitive vanilloid receptor-like protein.
Vanilloid receptor-1 (VR1, also known as TRPV1) is a thermosensitive, nonselective cation channel that is expressed by capsaicin-sensitive sensory afferents and is activated by noxious heat, acidic pH and the alkaloid irritant capsaicin. Although VR1 gene disruption results in a loss of capsaicin responses, it has minimal effects on thermal nociception. This and other experiments--such as those showing the existence of capsaicin-insensitive heat sensors in sensory neurons--suggest the existence of thermosensitive receptors distinct from VR1. Here we identify a member of the vanilloid receptor/TRP gene family, vanilloid receptor-like protein 3 (VRL3, also known as TRPV3), which is heat-sensitive but capsaicin-insensitive. VRL3 is coded for by a 2,370-base-pair open reading frame, transcribed from a gene adjacent to VR1, and is structurally homologous to VR1. VRL3 responds to noxious heat with a threshold of about 39 degrees C and is co-expressed in dorsal root ganglion neurons with VR1. Furthermore, when heterologously expressed, VRL3 is able to associate with VR1 and may modulate its responses. Hence, not only is VRL3 a thermosensitive ion channel but it may represent an additional vanilloid receptor subunit involved in the formation of heteromeric vanilloid receptor channels.


Varicella zoster virus in inflammatory bowel disease patients: what every gastroenterologist should know.
Primary Varicella Zoster virus (VZV) infection results in varicella (chickenpox) while its reactivation results in herpes zoster (HZ; shingles). Patients with Inflammatory Bowel Disease (IBD) are susceptible to complications of primary VZV infection and have an increased risk of HZ. Concerns of VZV and HZ infection in the IBD population has been highlighted by the emergence of JAK-inhibitors and their safety profile in this patient population such as tofacitinib for the treatment of ulcerative colitis (UC). The current pipeline of emerging therapies include novel molecules targeting multiple pathways including JAK/signal transducer and cytokine signalling pathways such as JAK/STAT. Hence VZV and HZ will be increasingly relevant for gastroenterologists treating IBD patients in light of these emerging therapies.


Reservoirs of antimicrobial resistance genes in retail raw milk.
It has been estimated that at least 3% of the USA population consumes unpasteurized (raw) milk from animal sources, and the demand to legalize raw milk sales continues to increase. However, consumption of raw milk can cause foodborne illness and be a source of bacteria containing transferrable antimicrobial resistance genes (ARGs). To obtain a comprehensive understanding of the microbiome and antibiotic resistome in both raw and processed milk, we systematically analyzed 2034 retail milk samples including unpasteurized milk and pasteurized milk via vat pasteurization, high-temperature-short-time pasteurization, and ultra-pasteurization from the United States using complementary culture-based, 16S rRNA gene, and metagenomic sequencing techniques. Raw milk samples had the highest prevalence of viable bacteria which were measured as all aerobic bacteria, coliform, and Escherichia coli counts, and their microbiota was distinct from other types of milk. 16S rRNA gene sequencing revealed that Pseudomonadaceae dominated raw milk with limited levels of lactic acid bacteria. Among all milk samples, the microbiota remained stable with constant bacterial populations when stored at 4 °C. In contrast, storage at room temperature dramatically enriched the bacterial populations present in raw milk samples and, in parallel, significantly increased the richness and abundance of ARGs. Metagenomic sequencing indicated raw milk possessed dramatically more ARGs than pasteurized milk, and a conjugation assay documented the active transfer of blaCMY-2, one ceftazidime resistance gene present in raw milk-borne E. coli, across bacterial species. The room temperature-enriched resistome differed in raw milk from distinct geographic locations, a difference likely associated with regionally distinct milk microbiota. Despite advertised "probiotic" effects, our results indicate that raw milk microbiota has minimal lactic acid bacteria. In addition, retail raw milk serves as a reservoir of ARGs, populations of which are readily amplified by spontaneous fermentation. There is an increased need to understand potential food safety risks from improper transportation and storage of raw milk with regard to ARGs. Video Abstract.


DWI cerebellar infarct volume as predictor of outcomes after endovascular treatment of acute basilar artery occlusion.
Preprocedural predictors of outcome in patients with acute basilar artery occlusion (ABAO) who have undergone endovascular treatment (EVT) remain controversial. Our aim was to determine if pre-EVT diffusion-weighted imaging cerebellar infarct volume (CIV) is a predictor of 90-day outcomes. We analyzed consecutive MRI-selected endovascularly treated patients with ABAO within the first 24 hours after symptom onset. Successful reperfusion was defined as a modified Thrombolysis in Cerebral Infarction score of 2b-3. Using the initial MRI, baseline CIV was calculated in mL on an apparent diffusion coefficient map reconstruction (Olea Sphere software). CIV was analyzed in univariate and multivariable models as a predictor of 90-day functional independence (modified Rankin Scale (mRS) 0-2) and mortality. According to receiver operating characteristic (ROC) analysis, the optimal cut-off was determined by maximizing the Youden index to evaluate the prognostic value of CIV. Of the 110 MRI-selected patients with ABAO, 64 (58.18%) had a cerebellar infarct. The median CIV was 9.6 mL (IQR 2.7-31.4). Successful reperfusion was achieved in 81.8% of the cases. At 90 days the proportion of patients with mRS ≤2 was 31.8% and the overall mortality rate was 40.9%. Baseline CIV was significantly associated with 90-day mRS 0-2 (p=0.008) in the univariate analysis and was an independent predictor of 90-day mortality (adjusted OR 1.79, 95% CI 1.25 to 2.54, p=0.001). The ROC analysis showed that a CIV ≥4.7 mL at the initial MRI was the optimal cut-off to discriminate patients with a higher risk of death at 90 days (area under the ROC curve (AUC)=0.74, 95% CI 0.61 to 0.87, sensitivity and specificity of 87.9% and 58.1%, respectively). In our series of MRI-selected patients with ABAO, pre-EVT CIV was an independent predictor of 90-day mortality. The risk of death was increased for baseline CIV ≥4.7 mL.


[Acupuncture--a complementary treatment in general practice].
Acupuncture is the complementary treatment most commonly used by general practitioners. This study describes the use of acupuncture among Norwegian general practitioners trained in acupuncture. By telephone or mail, a questionnaire was presented to 212 general practitioners who had completed training in complementary acupuncture. They were asked to describe the use and effect of acupuncture and their attitude towards acupuncture. Of the 111 physicians who replied (53%), 67 (60%) used acupuncture in their clinical practice. 78% had acupuncture courses of less than four weeks' duration only. 52% stated that acupuncture was the preferred treatment in more than 5% of their patients. About 70-80% used acupuncture as a supplement to conventional treatment. Acupuncture was commonly used in patients with musculoskeletal pain (93%), migraine (66%), and headache (63%), less often in patients with nausea, allergy, anxiety, sleep disturbances and gastrointestinal disorders. Improvement was reported in approximately three out of four patients. Lack of time was regarded as the major limitation to the use of acupuncture. Many general practitioners trained in complementary acupuncture use acupuncture as an integrated part of their clinical practice.


Update on Central Nervous System Effects of the Intersection of HIV-1 and SARS-CoV-2.
Research has shown myriad neurologic and mental health manifestations during the acute and subsequent stages of COVID-19 in people with HIV (PWH). This review summarizes the updates on central nervous system (CNS) outcomes following SARS-CoV-2 infection in PWH and highlight the existing knowledge gaps in this area. Studies leveraging electronic record systems have highlighted the excess risk of developing acute and lingering neurological complications of COVID-19 in PWH compared to people without HIV (PWoH). However, there is a notable scarcity of neuroimaging as well as blood and cerebrospinal fluid (CSF) marker studies that can confirm the potential synergy between these two infections, particularly in PWH receiving suppressive antiretroviral therapy. Considering the unclear potential interaction between SARS-CoV-2 and HIV, clinicians should remain vigilant regarding new-onset or worsening neurological symptoms in PWH following COVID-19, as they could be linked to either infection.


Prevalence of Caesarean sections in Enugu, southeast Nigeria: Analysis of data from the Healthy Beginning Initiative.
In order to meet the Sustainable Development Goal to decrease maternal mortality, increased access to obstetric interventions such as Caesarean sections (CS) is of critical importance. As a result of women's limited access to routine and emergency obstetric services in Nigeria, the country is a major contributor to the global burden of maternal mortality. In this analysis, we aim to establish rates of CS and determine socioeconomic or medical risk factors associated with having a CS in Enugu, southeast Nigeria. Data for this study originated from the Healthy Beginning Initiative study. Participant characteristics were obtained from 2300 women at baseline via a semi-structured questionnaire. Only women between the ages of 17-45 who had singleton deliveries were retained for this analysis. Post-delivery questionnaires were used to ascertain mode-of-delivery. Crude and adjusted logistic regressions with Caesarean as the main outcome are presented. In this sample, 7.22% women had a CS. Compared to women who lived in an urban setting, those who lived in a rural setting had a significant reduction in the odds of having a CS (aOR: 0.58; 0.38-0.89). Significantly higher odds of having a CS were seen among those with high peripheral malaria parasitemia compared to those with low parasitemia (aOR: 1.54; 1.04-2.28). This study revealed that contrary to the increasing trend in use of CS in low-income countries, women in this region of Nigeria had limited access to this intervention. Increasing age and socioeconomic proxies for income and access to care (e.g., having a tertiary-level education, full-time employment, and urban residence) were shown to be key determinants of access to CS. Further research is needed to ascertain the obstetric conditions under which women in this region receive CS, and to further elucidate the role of socioeconomic factors in accessing CS.


Prevalence of nonalcoholic fatty liver disease (NAFLD) and utility of FIBROspect II to detect liver fibrosis in morbidly obese Hispano-American patients undergoing gastric bypass.
Our study describes the prevalence of nonalcoholic steatohepatitis (NASH) and liver fibrosis in Hispano-American morbidly obese patients and the utility of different serum markers to predict significant liver fibrosis in this population. We perform a retrospective chart review of all patients undergoing Roux-en-Y gastric bypass with routine liver biopsy performed at Valley Baptist medical center during a 24-month period (2005-2006). Of 129 liver biopsies, only 25.7% had some degree of steatosis, but about 55% had NASH, and 30.9% had liver fibrosis. Of those patients with liver fibrosis, only 6.9% had moderate to severe fibrosis (stages 2-4), and only one patient had cirrhosis (0.7%). Of the 129 patients, only 92 had a FIBROspect score II in their chart, and they ranged from 9 to 95, with a mean of 28.3. Of these patients, 36 had a score less than 20, and none had significant fibrosis in their biopsy. FIBROspect II® score (cutoff <20) had a negative predictive value (NPV) of 100% (confidence interval (CI) 95%, 0.9035-1) positive predictive value (PPV) of 15% (CI 95%, 0.0838-0.2693), sensitivity of 100%, and specificity of 42% to predict stage 2 fibrosis or higher. NASH and liver fibrosis are present in a high percentage of morbidly obese patients. Liver function tests and ultrasound are not reliable tests to diagnose or rule out advance liver fibrosis. The use of FIBROspect II® score in the preoperative evaluation of morbidly obese patients can rule out significant liver fibrosis (stages 2-4) and avoid the morbidities related to liver biopsy.


Coxibs interfere with the action of aspirin by binding tightly to one monomer of cyclooxygenase-1.
Pain associated with inflammation involves prostaglandins synthesized from arachidonic acid (AA) through cyclooxygenase-2 (COX-2) pathways while thromboxane A(2) formed by platelets from AA via cyclooxygenase-1 (COX-1) mediates thrombosis. COX-1 and COX-2 are both targets of nonselective nonsteroidal antiinflammatory drugs (nsNSAIDs) including aspirin whereas COX-2 activity is preferentially blocked by COX-2 inhibitors called coxibs. COXs are homodimers composed of identical subunits, but we have shown that only one subunit is active at a time during catalysis; moreover, many nsNSAIDS bind to a single subunit of a COX dimer to inhibit the COX activity of the entire dimer. Here, we report the surprising observation that celecoxib and other coxibs bind tightly to a subunit of COX-1. Although celecoxib binding to one monomer of COX-1 does not affect the normal catalytic processing of AA by the second, partner subunit, celecoxib does interfere with the inhibition of COX-1 by aspirin in vitro. X-ray crystallographic results obtained with a celecoxib/COX-1 complex show how celecoxib can bind to one of the two available COX sites of the COX-1 dimer. Finally, we find that administration of celecoxib to dogs interferes with the ability of a low dose of aspirin to inhibit AA-induced ex vivo platelet aggregation. COX-2 inhibitors such as celecoxib are widely used for pain relief. Because coxibs exhibit cardiovascular side effects, they are often prescribed in combination with low-dose aspirin to prevent thrombosis. Our studies predict that the cardioprotective effect of low-dose aspirin on COX-1 may be blunted when taken with coxibs.


Stigma among Singaporean youth: a cross-sectional study on adolescent attitudes towards serious mental illness and social tolerance in a multiethnic population.
Stigma against mental illnesses is one of the significant obstacles faced by mental health service users and providers. It can develop at a young age and is also influenced by culture. Youths in Southeast Asian countries are under-represented in mental health research, thus this study aims to explore the dimensions of stigma and social tolerance and examine its correlates in the younger, multiethnic population of Singapore. An online survey collected data with sociodemographic questions, the Attitudes Towards Serious Mental Illness (Adolescent version) Scale, Social Tolerance Scale and an open-text question on words or phrases participants associated with the term 'mental illness'. Principal component analysis and multiple regression models were conducted to investigate the factor structure of the attitudes and social tolerance scales and their sociodemographic correlates. Participants included 940 youths aged 14-18 years old who were residing in Singapore at the time of the survey and were recruited through local schools. About a quarter of the students (22.6%) reported participating in mental health awareness campaigns while nearly half (44.5%) associated pejorative words and phrases with the term mental illness. The Attitudes Towards Serious Mental Illness (Adolescent version) Scale yielded five factors while the Social Tolerance Scale yielded two. Ethnicity, gender and nationality were significantly correlated with factors of both scales. Chinese youths showed higher sense of 'physical threat' and lower 'social tolerance' than those of other ethnicities. Females showed more 'wishful thinking', 'social concern' and 'social responsibility' towards the mentally ill than males. The dimensions of stigma and social tolerance are different in Asian cultures compared with Western cultures. Sociodemographic differences in attitudes towards the mentally ill were found among youths living in Singapore. Misconceptions and negative attitudes towards mental illness are common, demonstrating a clear need for effective stigma reduction campaigns.


Impaired subjective well-being in schizophrenia is associated with reduced anterior cingulate activity during reward processing.
Patients with schizophrenia have substantially reduced subjective well-being (SW) compared to healthy individuals. It has been suggested that diminished SW may be related to deficits in the neural processing of reward but this has not been shown directly. We hypothesized that, in schizophrenia, lower SW would be associated with attenuated reward-related activation in the reward network. Twenty patients with schizophrenia with a range of SW underwent a functional magnetic resonance imaging (fMRI) reward task. The brain activity underlying reward anticipation and outcome in schizophrenia was examined and compared to that of 12 healthy participants using a full factorial analysis. Region of interest (ROI) analyses of areas within the reward network and whole-brain analyses were conducted to reveal neural correlates of SW. Reward-related neural activity in schizophrenia was not significantly different from that of healthy participants; however, the patients with schizophrenia showed significantly diminished SW. Both ROI and whole-brain analyses confirmed that SW scores in the patients correlated significantly with activity, specifically in the dorsal anterior cingulate cortex (dACC), during both reward anticipation and reward outcome. This association was not seen in the healthy participants. In patients with schizophrenia, reduced activation of the dACC during multiple aspects of reward processing is associated with lower SW. As the dACC has been widely linked to coupling of reward and action, and the link to SW is apparent over anticipation and outcome, these findings suggest that SW deficits in schizophrenia may be attributable to reduced integration of environmental rewarding cues, motivated behaviour and reward outcome.


Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus.
Epidemiological and basic science evidence suggests that magnesium sulphate before birth may be neuroprotective for the fetus. To assess the effectiveness and safety of magnesium sulphate as a neuroprotective agent when given to women considered at risk of preterm birth. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (October 2006), CENTRAL (The Cochrane Library 2006, Issue 3), MEDLINE (1966 to October 2006), EMBASE (1980 to October 2006), Current Contents (1992 to October 2006), references of retrieved articles, and abstracts submitted to the Society for Pediatric Research (1996 to 2006). Randomised controlled trials of antenatal magnesium sulphate therapy given to women threatening or likely to give birth at less than 37 weeks' gestational age. We independently extracted data regarding clinical outcomes including paediatric mortality, neurologic outcome of survivors (including blindness, deafness, cerebral palsy and major neurosensory disability), and maternal complications and side-effects. At least two authors assessed trial eligibility and quality, and extracted data. Four trials (3701 babies) were eligible for this review. No statistically significant effect of antenatal magnesium sulphate therapy was detected on any major paediatric outcome, including mortality (e.g., paediatric mortality relative risk (RR) 0.97; 95% confidence interval (CI) 0.74 to 1.28; four trials; 3701 infants), and neurological outcomes in the first few years of life, including cerebral palsy (RR 0.77; 95% CI 0.56 to 1.06; four trials; 3701 infants), neurological impairments or disabilities. There were also no significant effects of antenatal magnesium therapy on combined rates of mortality with neurologic outcomes. There was a significant reduction in the rate of substantial gross motor dysfunction (RR 0.56; 95% CI 0.33 to 0.97; two trials; 2848 infants). There were higher rates of minor maternal side-effects in the magnesium groups, but no significant effects on major maternal complications. The role for antenatal magnesium sulphate therapy as a neuroprotective agent for the preterm fetus is not yet established. Given the possible beneficial effects of magnesium sulphate on gross motor function in early childhood, outcomes later in childhood should be evaluated to determine the presence or absence of later potentially important neurologic effects, particularly on motor or cognitive function. Further information will be available from one of the studies where outcomes are being evaluated again at eight to nine years of age, and from another trial currently in progress.


Clinical implications of incorporating genetic and non-genetic risk factors in CanRisk-based breast cancer risk prediction.
Breast cancer (BC) risk prediction models consider cancer family history (FH) and germline pathogenic variants (PVs) in risk genes. It remains elusive to what extent complementation with polygenic risk score (PRS) and non-genetic risk factor (NGRFs) data affects individual intensified breast surveillance (IBS) recommendations according to European guidelines. For 425 cancer-free women with cancer FH (mean age 40·6 years, range 21-74), recruited in France, Germany and the Netherlands, germline PV status, NGRFs, and a 306 variant-based PRS (PRS306) were assessed to calculate estimated lifetime risks (eLTR) and estimated 10-year risks (e10YR) using CanRisk. The proportions of women changing country-specific European risk categories for IBS recommendations, i.e. ≥20 % and ≥30 % eLTR, or ≥5 % e10YR were determined. Of the women with non-informative PV status, including PRS306 and NGRFs changed clinical recommendations for 31·0 %, (57/184, 20 % eLTR), 15·8 % (29/184, 30 % eLTR) and 22·4 % (41/183, 5 % e10YR), respectively whereas of the women tested negative for a PV observed in their family, clinical recommendations changed for 16·7 % (25/150), 1·3 % (2/150) and 9·5 % (14/147). No change was observed for 82 women with PVs in high-risk genes (BRCA1/2, PALB2). Combined consideration of eLTRs and e10YRs identified BRCA1/2 PV carriers benefitting from IBS <30 years, and women tested non-informative/negative for whom IBS may be postponed. For women who tested non-informative/negative, PRS and NGRFs have a considerable impact on IBS recommendations. Combined consideration of eLTRs and e10YRs allows personalizing IBS starting age. Horizon 2020, German Cancer Aid, Federal Ministry of Education and Research, Köln Fortune.


Creutzfeldt-Jakob disease and the risk from blood or blood products.
The occurrence of iatrogenic cases of Creutzfeldt-Jakob disease (CJD) and the isolation of infectivity in some laboratory transmission studies in transmissible spongiform encephalopathies raises the possibility that CJD might be accidentally transmissible through blood or blood products. Epidemiological evidence, although not conclusive, does not suggest that classical CJD is transmitted through this route. However, new variant CJD (nvCJD) might pose greater risks of accidental transmission of infection and mechanisms to reduce the theoretical risk are under consideration. The theoretical risks from CJD and nvCJD must be balanced against the established therapeutic benefits of blood and blood products.


Interaction between smoking status and dietary selenium intake affects PSA: A cross-sectional study.
Conflicting results regarding the impact of selenium on reducing prostate cancer have been reported. The current analysis aimed to understand whether there are potential factors affecting the relationship between selenium and prostate cancer. To clarify the relationship between dietary selenium intake and prostate cancer, we evaluated the correlation between dietary selenium intake and prostate-specific antigen (PSA) based on the National Health and Nutrition Examination Survey (NHANES) database. After screening the NHANES survey data from 2005 to 2010, data for 3,614 of 31,034 participants were considered suitable to include in our study. Dietary selenium intake was the independent variable of our study, while PSA was the dependent variable. We stratified participants into current, former, and never smokers and performed an interaction test on the relationship between selenium intake and PSA using multivariable logistic regression for each smoking-status subgroup. For our subgroup analysis, we grouped participants based on smoking status and investigated the association between dietary selenium intake and PSA levels. Among the 242 participants with a PSA level of 4 or higher, the mean age was 58.5 years (±12.1). After adjusting for covariates, we did not find a significant association between dietary selenium and the odds of having a high PSA level. However, we observed a significant interaction between smoking status and dietary selenium in relation to PSA levels (P = .007). Specifically, smokers had lower odds of having high PSA levels, while nonsmokers had higher odds. This suggests that smoking status may modify the effect of dietary selenium on PSA levels. Our findings suggest that smoking status affects the relationship between dietary selenium intake and PSA and that smokers are at lower odds of having a high PSA level.


[Percutaneous drainage of amebic hepatic abscess by guided ultraound. Preliminary results].
Amebic hepatic abscess (AHA) is the most frequent extraintestinal complication of amebiasis. Over time, its treatment has gone through some changes and at present is based on amebicides and in some cases, percutaneous drainage. The objective of this work is to present our experience with percutaneous drainage by means of guided ultrasound in patients with AHA. In this work, we include 170 patients admitted to the Gastroenterology Unit of the Hospital General de Zona No. 1, (IMSS) in Mexico City during a period of eight years (1990-1997). These cases included the following criteria: Failure to medical therapy, AHA of liquid matter greater than 5 cm determined by ultrasound; risk of rupture, prolonged incapacity with no data of toxico-infection, accessible drainage route; availability of operating room before risk of complication, and normal coagulation tests. A modified Seldinger's technique was utilized. A single punction was carried out in 131 patients, who had only one abscess. Thirty-nine patients required a second evacuation on presenting two abscesses, and in four cases, a third evacuation was required due to the presence of three or more abscesses. Only one case required an urgent surgical procedure due to abscess rupture to pleura. Five patients suffered complications, including the latter. The remaining four patients had a spontaneous resolution. All patients were released during the 24 hours following surgery, and no patient required hospitalization. For this reason, this can be considered a procedure that in the expert hands of interventionist radiologists, has less morbidity. This work will be carried out to 10 years.


Benchmarking EEG-based Cross-dataset Driver Drowsiness Recognition with Deep Transfer Learning.
It usually takes a long time to collect data for calibration when using electroencephalography (EEG) for driver drowsiness monitoring. Cross-dataset recognition is desirable since it can significantly save the calibration time when an existing dataset is used. However, the recognition accuracy is affected by the distribution drift problem caused by different experimental environments when building different datasets. In order to solve the problem, we propose a deep transfer learning model named Entropy-Driven Joint Adaptation Network (EDJAN), which can learn useful information from source and target domains simultaneously. An entropy-driven loss function is used to promote clustering of target-domain representations and an individual-level domain adaptation technique is proposed to alleviate the distribution discrepancy problem of test subjects. We use two public driving datasets SEEG-VIG and SADT to test the model on the cross-dataset setting. The proposed model achieved an accuracy of 83.3% when SADT is used as source domain and SEED-VIG is used as target domain and 76.7% accuracy on the reverse setting, which is higher than the other SOTA methods. The results are further analyzed with both global and local interpretation methods. Our work illuminates a promising direction of using EEG for calibration-free driver drowsiness recognition.


Human papillomavirus and the three group metaphase figure as markers of an increased risk for the development of cervical carcinoma.
In this study, the presence of atypical mitotic figures and human papilloma virus (HPV) genomes was related to the degree of cervical intraepithelial neoplasia (CIN) or microinvasive carcinoma (MIC) as found in 94 paraffin-embedded biopsies from cervical lesions. The results showed that the frequency of three group metaphase (TGM) figures, a special kind of atypical mitotic figure, as well as the presence of HPV 16 and 18 genomes increased with the degree of cervical intraepithelial neoplasia. TGM figures were observed in 24% of CIN2, up to 61% in CIN3 lesions, and in 83% of the microinvasive cervical carcinomas. HPV genomes were detected in 15% of CIN1, up to 75% in CIN3 lesions, and in 92% of the invasive carcinomas of the cervix. The combination of these two markers showed even a better association with a higher degree of cervical intraepithelial neoplasia. The results of these studies suggest that detection of particular HPV types, mainly HPV 16 and 18, and the presence of TGM figures can be considered as markers that indicate an increased risk for progression of cervical intraepithelial neoplasia to invasive carcinoma.


Whole genome expression profiling shows that BRG1 transcriptionally regulates UV inducible genes and other novel targets in human cells.
UV irradiation is known to cause cyclobutane pyrimidine dimers (CPDs) and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs), and plays a large role in the development of cancer. Tumor suppression, through DNA repair and proper cell cycle regulation, is an integral factor in maintaining healthy cells and preventing development of cancer. Transcriptional regulation of the genes involved in the various tumor suppression pathways is essential for them to be expressed when needed and to function properly. BRG1, an ATPase catalytic subunit of the SWI/SNF chromatin remodeling complex, has been identified as a tumor suppressor protein, as it has been shown to play a role in Nucleotide Excision Repair (NER) of CPDs, suppress apoptosis, and restore checkpoint deficiency, in response to UV exposure. Although BRG1 has been shown to regulate transcription of some genes that are instrumental in proper DNA damage repair and cell cycle maintenance in response to UV, its role in transcriptional regulation of the whole genome in response to UV has not yet been elucidated. With whole genome expression profiling in SW13 cells, we show that upon UV induction, BRG1 regulates transcriptional expression of many genes involved in cell stress response. Additionally, our results also highlight BRG1's general role as a master regulator of the genome, as it transcriptionally regulates approximately 4.8% of the human genome, including expression of genes involved in many pathways. RT-PCR and ChIP were used to validate our genome expression analysis. Importantly, our study identifies several novel transcriptional targets of BRG1, such as ATF3. Thus, BRG1 has a larger impact on human genome expression than previously thought, and our studies will provide inroads for future analysis of BRG1's role in gene regulation.


A Nationwide Study of Inpatient Admissions, Mortality, and Costs for Patients with Cirrhosis from 2005 to 2015 in the USA.
Liver cirrhosis is a substantial health burden in the USA, but population-based data regarding the trend and medical expenditure are limited and outdated. We investigated the trends of inpatient admissions, costs, and inpatient mortality from 2005 to 2015 among cirrhotic patients. A retrospective analysis was conducted using the National Inpatient Sample database. We adjusted the costs to 2015 US dollars using a 3% inflation rate. National estimates of admissions were determined using discharge weights. We identified 1,627,348 admissions in cirrhotic patients between 2005 and 2015. From 2005 to 2015, the number of weighted admissions in cirrhotic patients almost doubled (from 505,032 to 961,650) and the total annual hospitalization cost in this population increased three times (from 5.8 to 16.3 billion US dollars). Notably, admission rates varied by liver disease etiology, decreasing from 2005 to 2015 among patients with hepatitis C virus (HCV)-related cirrhosis while increasing (almost tripled) among patients with nonalcoholic fatty liver disease (NAFLD)-related cirrhosis. The annual inpatient mortality rate per 1000 admissions overall decreased from 63.8 to 58.2 between 2005 and 2015 except for NAFLD (27.2 to 35.8) (P < 0.001). Rates and costs of admissions in cirrhotic patients have increased substantially between 2005 and 2015 in the USA, but varied by liver disease etiology, with decreasing rate for HCV-associated cirrhosis and for HBV-associated cirrhosis but increasing for NAFLD-associated cirrhosis. Inpatient mortality also increased by one-third for NAFLD, while it decreased for other diseases. Cost also varied by etiology and lower for HCV-associated cirrhosis.


Pt-Se-Bonded Nanoprobe for High-Fidelity Detection of Non-small Cell Lung Cancer and Enhancement of NIR II Photothermal Therapy.
Non-small cell lung cancer (NSCLC) accounts for a high proportion of lung cancer cases globally, but early detection remains challenging, and insufficient oxygen supply at tumor sites leads to suboptimal treatment outcomes. Therefore, the development of core-shell Au@Pt-Se nanoprobes (Au@Pt-Se NPs) with peptide chains linked through Pt-Se bonds was designed and synthesized for NSCLC biomarker protein calcium-activated neutral protease 2 (CAPN2) and photothermal therapy (PTT) enhancement. The NP can be specifically cleaved by CAPN2, resulting in fluorescence recovery to realize the detection. The Pt-Se bonds exhibit excellent resistance to biologically abundant thiols such as glutathione, thus avoiding "false-positive" results and enabling precise detection of NSCLC. Additionally, the platinum (Pt) shell possesses catalase-like properties that catalyze the generation of oxygen from endogenous hydrogen peroxide within the tumor, thereby reducing hypoxia-inducible factor-1α (HIF-1α) levels and alleviating the hypoxic environment at the tumor site. The Au@Pt-Se NPs exhibit strong absorption bands, enabling the possibility of PTT in the near-infrared II region (NIR II). This study presents an effective approach for the early detection of NSCLC while also serving as an oxygen supplier to alleviate the hypoxic environment and enhance NIR II PTT.


Chemical alterations in cell envelopes of polymyxin-resistant mutants of Pseudomonas aeruginosa grown in the absence or presence of polymyxin.
The polymyxin-resistant mutant strains H181 and H185 of Pseudomonas aeruginosa, after growth in the absence or presence of polymyxin, were compared with the polymyxin-sensitive H103 strain as to their cell envelope protein composition (determined by slab polyacrylamide gel electrophoresis) and their lipid composition. When grown in the absence of polymyxin, the H181 and H185 strains had an increased content of the outer membrane protein H1 with a decreased content of the outer membrane proteins D2 and F. After growth in the presence of polymyxin, the content of H1, D2, and F were all decreased. Significant alterations in the lipid composition of the H181 and H185 strains were found after growth in the absence of polymyxin. These lipid alterations were enhanced upon growth in the presence of polymyxin, with both strains having a reduced content of phosphatidylethanolamine and phosphatidylglycerol and an increased content of diphosphatidylglycerol and an unidentified lipid thought to be a neutral lipid. Other workers have proposed that an increased content of H1 protein is the molecular basis for polymyxin resistance in the H181 and H185 strains. Our observations make this hypothesis appear unlikely.


Expected small left heart size in the presence of congenital diaphragmatic hernia: Fetal values and Z-scores for infants confirmed to have no heart disease postnatally.
In fetuses with left-sided congenital diaphragmatic hernia (CDH), left heart structures may appear small, but usually normalize after birth in the absence of structural cardiac anomalies. To decrease the possibility of an erroneous diagnosis of structural heart disease, we identify normal values for left heart structures in the presence of left CDH and secondarily investigate the relationship of left heart size and survival to neonatal hospital discharge. Left heart structures [mitral valve (MV) and aortic valve (AoV) annulus diameter, left ventricle (LV) length and width] were measured by fetal echocardiogram in fetuses with left CDH and no congenital heart disease. We generated linear regression models to establish the relationship of gestational age for each left heart structure using data from fetuses who survived after birth. We calculated z-scores (normalized to gestational age), and assessed the relationship of survival to the size of each structure. One hundred forty-two fetuses underwent fetal echocardiogram (median 25 weeks' gestation, IQR 23, 27 weeks). Left heart structures were deemed small when using published normative data from unaffected fetuses (z-scores: MV -1.09 ± 1.35, AoV -2.12 ± 1.16, LV length -1.36 ± 1.24, LV width -4.79 ± 0.79). CDH-specific models derived from log-transformed values yielded left-shifted distributions, reflecting the small structures (mean z-score lower by: MV 0.99 ± 0.30, AoV 2.04 ± 0.38, LV length 1.30 ± 0.36, and LV width 4.69 ± 0.28; p < 0.0001 for all comparisons). Non-survivors had worse z-scores than survivors for all measurements, but this did not reach statistical significance. Log-transformed linear models generated new normative data for fetal left heart structures in left CDH, which may be used to allay antenatal concerns regarding structural left heart anomalies. There were no significant differences in z-scores between survivors and non-survivors, suggesting that in the absence of true structural disease, cardiac evaluation is not predictive in isolation and that causes of mortality are likely multifactorial in this population.


Self-Evaluation Strategies in College Women Trying to Lose Weight: The Relative Use of Objective and Social Comparison Information.
We examined patterns of self-evaluative information use in a sample of college women who were trying to lose weight (N = 306). Participants described their weight loss experiences and answered questions about their self-evaluative activity via an online survey. The analysis strategy examined the relative use of four types of self-evaluative information (objective, upward social comparison, lateral social comparison, and downward social comparison) to meet three basic self-evaluative motives (accurate self-assessment, self-enhancement, and self-improvement). We also examined the role that dissatisfaction, uncertainty, importance, and self-esteem played in the relative use of information and the relationship of these factors on weight loss success. Our findings support previous research showing the primacy of accurate and self-improvement motives in the domain of weight loss and the usefulness of lateral social comparison information for meeting all three motives. Women evaluating their weight reported using upward social comparison information most often, followed by objective information. Lateral and upward social comparison information were rated as more useful than downward social comparison information for meeting accuracy and self-improvement motives. Both lateral and downward social comparison information were reported as especially useful for self-enhancement, with upward social comparison information rated as least useful. Our study utilized an integrative approach for understanding self-evaluative processes in the area of college women's weight loss. We found general support for our hypotheses regarding well-documented patterns of social comparison information usefulness for meeting three self-evaluative motives. Our data also support earlier research arguing that it is important to view information use in the context of multiple self-evaluative motives.


Small interfering RNA suppression of polyamine analog-induced spermidine/spermine n1-acetyltransferase.
N1,N11-diethylnorspermine (DENSPM) is a polyamine analog that down-regulates polyamine biosynthesis and potently upregulates the polyamine catabolic enzyme spermidine/spermine N1-acetyltransferase (SSAT). In certain cells, such as SKMEL-28 human melanoma cells, induction of SSAT is associated with rapid apoptosis. In this study, we used small interfering RNA (siRNA) to examine the role of SSAT induction in mediating polyamine pool depletion and apoptosis. siRNA duplexes were designed to target three independent sites in the SSAT mRNA coding region (siSSAT). When transfected under nontoxic conditions, two of the duplexes selectively reduced basal SSAT mRNA in HEK-293 cells by >80% and prevented DENSPM-induced SSAT mRNA by 95% in SK-MEL-28 cells. Treatment of SK-MEL-28 cells with 10 muM DENSPM in the presence of 83 nM siSSAT selectively prevented the 1400-fold induction of SSAT activity by approximately 90% and, in turn, prevented analog depletion of spermine (Spm) pools by approximately 35%. siSSAT also prevented DENSPM-induced cytochrome c release and caspase-3 cleavage at 36 h and apoptosis at 48 h as measured by annexin V staining. Overall, the data directly link analog induction of SSAT to Spm pool depletion and to caspase-dependent apoptosis in DENSPM-treated SK-MEL-28 cells. This represents the first use of siRNA technology directed toward a polyamine gene and the first unequivocal demonstration that SSAT induction initiates events leading to polyamine analog-induced apoptosis.


The value of simulation-based training in the path to laparoscopic urological proficiency.
Numerous factors have reduced the training opportunities of surgical residents in the operating room. There is also the question of patient's safety. This gives a need for increased training opportunities outside the operating room. We look if there is an added value in simulation-based training (SBT) in the acquisition of laparoscopic skills. Incorporating SBT into the medical students curriculum reduces surgical complication rates in the operating room. Reduction in opportunities to train surgical skills in the operating room, increased complexity of surgical procedures, and justified concerns for patients' safety require training opportunities outside the operating room. Data proves that skills, acquired in the lab during SBT, are transferable to the operating room. Moreover, incorporating an evidence-based laparoscopic simulation curriculum shortens the clinical learning curve and reduces surgical adverse events.


Multirhythmicity in an optoelectronic oscillator with large delay.
An optoelectronic oscillator exhibiting a large delay in its feedback loop is studied both experimentally and theoretically. We show that multiple square-wave oscillations may coexist for the same values of the parameters (multirhythmicity). Depending on the sign of the phase shift, these regimes admit either periods close to an integer fraction of the delay or periods close to an odd integer fraction of twice the delay. These periodic solutions emerge from successive Hopf bifurcation points and stabilize at a finite amplitude following a scenario similar to Eckhaus instability in spatially extended systems. We find quantitative agreements between experiments and numerical simulations. The linear stability of the square waves is substantiated analytically by determining the stable fixed points of a map.


Sepsis episodes caused by pressure injuries in critical illness: a retrospective observational cohort study.
Critically-ill patients (CIPs) with pressure injuries (PIs) may develop bloodstream infections (BSIs). To identify predisposing factors and discuss diagnosis and management of sepsis-related PIs in CIPs. The records of CIPs in the intensive care unit (ICU) between January 1, 2014, and January 1, 2020, with PI with sepsis-diagnoses and with different site cultures that were positive concurrent with bloodstream-cultures were retrospectively reviewed. Ninety-one sepsis episodes were included in the study. Low albumin level (U = 382.00, P = .006), renal failure (odds ratio [OR], 0.108 [95% CI, 0.015-0.783]; P = .025), and length of ICU stay (U = 130.00, P < .001) were identified as risk factors of BSIs due to PIs. The probability of BSI during a sepsis episode was lower in CIPs with PIs with higher C-reactive protein levels (U = 233.00, P < .001) and whose injury resulted from trauma or surgery (OR, 0.101 [95% CI, 0.016-0.626]; P = .014). The mortality was higher in CIPs with PI-induced BSIs (OR, 0.051 [95% CI, 0.008-0.309]; P = .001). Pressure injury-induced sepsis was associated with a high risk of 28-day mortality. The findings suggest that CIPs with PI are at increased risk of BSIs if they have low albumin levels, renal-failure, and prolonged ICU stay during sepsis episodes.


Childhood fever: Parental paracetamol administration after consulting out-of-hours general practice.
Background: Current guidelines emphasise prudent use of paracetamol in febrile children without pain. Little evidence is available on paracetamol administration by parents in general and post-GP-consultations.Objectives: To investigate if and how often parents of febrile children administer paracetamol to their child after consulting a GP during out-of-hours care. To explore if condition (painful or not), socio-economic status and age influenced this behaviour.Methods: This was a pre-planned secondary study, attached to an RCT (n = 25,355) that studied the effect of an illness-focused interactive booklet on antibiotic prescriptions in febrile children between three months and 12 years, at 20 GP out-of-hours centres across the Netherlands. Baseline data and ICPC codes were retrieved from the GP out-of-hours centre database. During a telephone survey two weeks after consulting a GP out-of-hours centre, a random sample of parents was asked if and how often they had given their child paracetamol.Results: Parents of 548 children participated. Most parents administrated paracetamol for two weeks after consulting (83.8%). Children received 11 doses on average during follow-up (maximum 72 doses). Paracetamol administration increased with age. Age three to six months received paracetamol in 68% (17/25) of the cases versus 89.6% (121/135) in children aged five to twelve years. Frequency of paracetamol administration was similar for most common infections, regardless of being painful or painless.Conclusion: Most children who consulted out-of-hours general practice for fever and common infections received paracetamol at home during their illness episode, regardless of a painful condition being present. Paracetamol administration increased with age.


[Treatment of linea alba hernia and diastasis of rectus abdominis].
The asynchronous development of structural and metabolic disorders of aponeurosis, leading to the development of defects in sheath of the rectus abdominis is the major factor of hernia of linea alba formation. Development of diastasis of m. rectus abdominis is caused by primary structural and metabolic changes of myocytes caused by the extreme overload. The important factor of the operation is restoration of anatomic and physiologic parameters of the abdominal wall by bringing mm. rectus abdominis together, shortening and enforsing of aponeurosis makes it possible to distribute regularly the load on the aponeurotic sheath of musculi recti.


High-throughput automated luminescent magnetic particle-based immunoassay to monitor human exposure to pyrethroid insecticides.
We have developed a sensitive, automated, competitive chemiluminescent immunoassay for the detection of 3-phenoxybenzoic acid (3-PBA), a metabolite common to many pyrethroid insecticides. The system uses a competitive hapten-protein conjugate that has been labeled with an acridinium ester as the chemiluminescent probe and secondary antibody-coated paramagnetic particles for the separation. After the immunoassay reagents and samples are combined for the competitive incubation step, a fully automated system is used to load the postincubation mixture into a delivery cuvette, facilitating the subsequent magnetic separation of the immunocomplex and the measurement of chemiluminescent signal for quantification. The immunoassay format described here supports the requirement for high throughput necessary for monitoring large numbers of samples in population-based studies. The optimized immunoassay was more sensitive than the conventional enzyme immunoassay in buffer (IC(50) = 0.1 and 2 microg/L, respectively). The mixed-mode solid-phase extraction used for sample preparation to reduce possible urinary matrix effects allowed the accurate measurement of 3-PBA levels as low as 1 microg/L. The automated chemiluminescent immunoassay described here is sensitive, simple to use, and more rapid than the previously reported standard microplate assay.


Temporal IgG Subtype Changes in Recurrent Idiopathic Membranous Nephropathy.
Determination of the IgG subtypes within the immune deposits in membranous nephropathy (MN) may be helpful in the differential diagnosis. IgG4 is the predominant subtype in idiopathic MN and recurrent MN, while IgG1, IgG2, and IgG3 subtypes are more common in secondary MN and de novo disease in the allograft. The temporal change of IgG subclasses in individual patients and its correlation with clinical variables have not been studied. We reviewed all posttransplantation protocol and indication biopsies (49) in 18 patients with recurrent MN who underwent transplantation at our center between 1998 and 2013 and performed IgG subtyping (IgG1-4). We tested serum for M-type phospholipase A2 receptor (PLA2 R) autoantibodies or performed PLA2 R antigen staining on the kidney biopsy. IgG4 was the (co)dominant IgG subtype in 10 of 14 biopsies at the diagnosis of recurrence regardless of PLA2 R association. In 8 of 12 transplantations with serial biopsies, the (co)dominant subtype did not change over time. There was a trend toward IgG1 and IgG3 (co)dominance in biopsies >1 year from recurrence and more IgG1 (co)dominant subtyping in the setting of more-advanced EM deposits. Treatment with rituximab did not affect the IgG subtype. In conclusion, the dominant IgG subtype did not change over time in recurrent MN.


Beta-receptors and stress protein 70 expression in hypoxic myocardium of rainbow trout and chinook salmon.
We examined the in vivo effect of acute hypoxemia on myocardial cell-surface (sarcolemmal) beta-adrenoreceptor density (Bmax) and binding affinity (KD) and on stress protein 70 (sp70) expression by exposing rainbow trout (Oncorhynchus mykiss; 2.1-2.7 kg) to hypoxic water (3 mg/l O2) at 15 degrees C for 6 h. This degree of hypoxia was the minimum O2 level that these trout could tolerate without losing equilibrium and struggling violently. Hypoxic exposure reduced arterial PO2 (PaO2) from 98 to 26 mmHg and arterial oxygen content (CaO2) from 10.8 to 7.4 vol/100 vol, but did not elevate epinephrine and norepinephrine levels above 10 and 30 nM, respectively. Despite the substantial reduction in blood oxygen status, the Bmax and KD of myocardial cell-surface beta-adrenoreceptors were unaffected by 6 h of hypoxic exposure. In addition, acute hypoxemia did not increase myocardial sp70 expression. The failure of short-term hypoxia to decrease trout myocardial beta-adrenoreceptor density clearly contrasts with the established hypoxia-mediated down-regulation shown for mammals. To further investigate the influence of low PO2 on salmonid myocardial beta-adrenoreceptors, binding studies were performed on the spongy (continuously exposed to deoxygenated venous blood) and compact (perfused by oxygenated blood supplied by the coronary artery) myocardia of chinook salmon. The spongy myocardium has adapted to its microenvironment of continuous low PO2 by having 14% more cell-surface beta-adrenoreceptors compared with the compact myocardium. There was no tissue-specific difference in KD and no evidence of sexual dimorphism in Bmax or KD. We conclude from our studies that the salmonid heart is well adapted for sustained performance under hypoxic conditions. We found that wild chinook salmon had 2.8 x more cell-surface beta-adrenoreceptors compared with hatchery-reared rainbow trout. This difference suggests a significant degree of plasticity exists for fish myocardial beta-adrenoreceptors. The signals underlying such differences await further study, but are not likely to include moderate hypoxia and sexual dimorphism.


In silico studies on DARC.
The Duffy Antigen/Receptor for Chemokine (DARC) is a seven segment transmembrane protein. It was firstly discovered as a blood group antigen and was the first specific gene locus assigned to a specific autosome in man. It became more famous as an erythrocyte receptor for malaria parasites (Plasmodium vivax and Plasmodium knowlesi), and finally for chemokines. DARC is an unorthodox chemokine receptor as (i) it binds chemokines of both CC and CXC classes and (ii) it lacks the Asp-Arg-Tyr consensus motif in its second cytoplasmic loop hence cannot couple to G proteins and activate their signaling pathways. DARC had also been associated to cancer progression, numerous inflammatory diseases, and possibly to AIDS. In this review, we will summarize important biological data on DARC. Then we shall focus on recent development of the elaboration and analyzes of structural models of DARC. We underline the difficulty to propose pertinent structural models of transmembrane protein using comparative modeling process, and other dedicated approaches as the Protein Blocks. The chosen structural models encompass most of the biochemical data known to date. Finally, we present recent development of protein-protein docking between DARC structural models and CXCL-8 structures. We propose a hierarchical search based on separated rigid and flexible docking.


Genetic variations and alternative splicing: the Glioma associated oncogene 1, GLI1.
Alternative splicing is a post-transcriptional regulatory process that is attaining stronger recognition as a modulator of gene expression. Alternative splicing occurs when the primary RNA transcript is differentially processed into more than one mature RNAs. This is the result of a variable definition/inclusion of the exons, the sequences that are excised from the primary RNA to form the mature RNAs. Consequently, RNA expression can generate a collection of differentially spliced RNAs, which may distinctly influence subsequent biological events, such as protein synthesis or other biomolecular interactions. Still the mechanisms that control exon definition and exon inclusion are not fully clarified. This mini-review highlights advances in this field as well as the impact of single nucleotide polymorphisms in affecting splicing decisions. The Glioma-associated oncogene 1, GLI1, is taken as an example in addressing the role of nucleotide substitutions for splicing regulation.


The role of metastasis-associated protein 1 in prostate cancer progression.
Distinguishing aggressive prostate cancer from indolent disease represents an important clinical challenge, as current therapy requires over treating men with prostate cancer to prevent the progression of a few cases. Expression of the metastasis-associated protein 1 (MTA1) has previously been found to be associated with progression to the metastatic state in various cancers. Analyzing DNA microarray data, we found MTA1 to be selectively overexpressed in metastatic prostate cancer compared with clinically localized prostate cancer and benign prostate tissue. These results were validated by demonstrating overexpression of MTA1 in metastatic prostate cancer by immunoblot analysis. MTA1 protein expression was evaluated by immunohistochemistry in a broad spectrum of prostate tumors with tissue microarrays containing 1940 tissue cores from 300 cases. Metastatic prostate cancer demonstrated significantly higher mean MTA1 protein expression intensity (score = 3.4/4) and percentage of tissue cores staining positive for MTA1 (83%) compared with clinically localized prostate cancer (score = 2.8/4, 63% positive cores) or benign prostate tissue (score = 1.5/4, 25% positive cores) with a mean difference of 0.54 and 1.84, respectively (P < 0.00001 for both). Paradoxically, for localized disease, higher MTA1 protein expression was associated with lower rates of prostate specific antigen recurrence after radical prostatectomy for localized disease. In summary, this study identified an association of MTA1 expression and prostate cancer progression.


Phytochemistry and pharmacology of plants in the genus Chaenomeles.
Chaenomeles plants belong to the Rosaceae family and include five species, Chaenomeles speciosa (Sweet) Nakai, Chaenomeles sinensis (Thouin) Koehne, Chaenomeles japonica (Thunb.) Lindl, Chaenomeles cathayensis (Hemsl.) Schneid and Chaenomeles thibetica Yu. Chaenomeles plants are found and cultivated in nearly every country worldwide. China serves as both the origin and distribution hub for the plants in the Chaenomeles genus, and all Chaenomeles species except for C. japonica are indigenous to China. Chaenomeles spp. is a type of edible medicinal plant that has been traditionally used in China to treat various ailments, such as rheumatism, cholera, dysentery, enteritis, beriberi, and scurvy. A variety of chemical constituents have been extracted from this genus, including terpenoids, phenolics, flavonoids, phenylpropanoids and their derivatives, benzoic acid derivatives, biphenyls, oxylipins, and alkaloids. The biological activity of some of these constituents has already been evaluated. Pharmacological investigations have demonstrated that the plants in the genus Chaenomeles exhibit anti-inflammatory, analgesic, antioxidant, antihyperglycemic, antihyperlipidemic, gastrointestinal protective, antitumor, immunomodulatory, antibacterial, antiviral, hepatoprotective, neuroprotective and other pharmacological activities. The objective of this review is to provide a comprehensive and up-to-date summary of the available information on the genus Chaenomeles to serve as a valuable reference for further investigations.


Local capacity, innovative entrepreneurial places and global connections: an overview.
The globalisation trend of the past few decades, driven to a large extent by the proliferation of GVCs, has led to a set of significant changes in patterns of technology upgrading and new modes of interaction between domestic technology efforts and external sources of technological knowledge. Whether this new dynamic will lead to continuing increase in the economic importance of emerging economies will ultimately depend on whether their productivity growth will be driven by technology upgrading, requiring active and coordinated activity orchestrated by a variety of state and non-state actors under diverse sectoral, regional and national innovation systems. The new dynamic also reinforces the focus on local-global interfaces which becomes ever more important once we recognize that in the 21st century technology upgrading challenges depend much more on improvements in connectivity and on the industrial ecosystem. Still, the globalization process experienced in the past few decades-reflected in this collection of papers-may need to be recalibrated in the face of the drastic geopolitical changes that the process itself has brought about.


Metabolite quantification by NMR and LC-MS/MS reveals differences between unstimulated, stimulated, and pure parotid saliva.
Saliva is a readily available biofluid that is sensitive to metabolic changes and can be collected through rapid and non-invasive collection procedures, and it shows great promise for clinical metabolomic studies. This work studied the metabolite composition of, and the differences between, saliva samples collected by unstimulated spitting/drooling, paraffin chewing-stimulated spitting, and parotid gland suction using targeted nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) for metabolite quantification. As applied here, these two analytical techniques provide complementary metabolite information and together extend the metabolome coverage with robust NMR quantification of soluble metabolites and sensitive targeted LC-MS/MS analysis of bioactive lipids in specific metabolic pathways. The NMR analysis was performed on ultrafiltrated (3kDa cutoff) saliva samples and resulted in a total of 45 quantified metabolites. The LC-MS/MS analysis was performed on both filtered and unfiltered samples and resulted in the quantification of two endocannabinoids (AEA and PEA) and 22 oxylipins, which at present is the most comprehensive targeted analysis of bioactive lipids in human saliva. Important differences in the metabolite composition were observed between the three saliva sample collection methods, which should be taken into consideration when designing metabolomic studies of saliva. Furthermore, the combined use of the two metabolomics platforms (NMR and LC-MS/MS) proved to be viable for research and clinical studies of the salivary metabolome.


[Feeding behaviour of Anopheles funestus resting females in Senegal].
The feeding behaviour of An. funestus resting females was studied in eleven sites in Senegal along a west-east transect in two biogeographical zones (the Sudanese and Sudanese-Guinean zones) by an ELISA technique. Mosquitoes were collected by pyrethrum spray catches. For the 1563 blood meals tested, the main hosts were humans, cows, sheep and horses representing respective proportions of 85%, 9.9%, 1.3% and 3.8%. No blood meal was taken on chicken. The percentage of non-reacting blood meals was 2.6%. A heterogenity of feeding behaviour was observed in the sample locations. The anthropophilic rates were higher in the northern Sudanese zone as versus the southern Sudanese and Sudano-Guinean zones.


Proteomics-Based Tools for Evaluation of Cell-Free Protein Synthesis.
Cell-free protein synthesis (CFPS) has the potential to produce enzymes, therapeutic agents, and other proteins, while circumventing difficulties associated with in vivo heterologous expression. However, the contents of the cell-free extracts used to carry out synthesis are generally not characterized, which hampers progress toward enhancing yield or functional activity of the target protein. We explored the utility of mass spectrometry (MS)-based proteomics for characterizing the bacterial extracts used for transcribing and translating gene sequences into proteins as well as the products of CFPS reactions. Full proteome experiments identified over 1000 proteins per reaction. The complete set of proteins necessary for transcription and translation were found, demonstrating the ability to define potential metabolic capabilities of the extract. Further, MS-based techniques allowed characterization of the CFPS product and provided insight into the synthesis reaction and potential functional activity of the product. These capabilities were demonstrated using two different CFPS products, the commonly used standard green fluorescent protein (GFP, 27 kDa) and the polyketide synthase DEBS1 (394 kDa). For the large, multidomain DEBS1, substantial premature termination of protein translation was observed. Additionally, MS/MS analysis, as part of a conventional full proteomics workflow, identified post-translational modifications, including the chromophore in GFP, as well as the three phosphopantetheinylation sites in DEBS1. A hypothesis-driven approach focused on these three sites identified that all were correctly modified for DEBS1 expressed in vivo but with less complete coverage for protein expressed in CFPS reactions. These post-translational modifications are essential for functional activity, and the ability to identify them with mass spectrometry is valuable for judging the success of the CFPS reaction. Collectively, the use of MS-based proteomics will prove advantageous for advancing the application of CFPS and related techniques.


Adsorption of methyl orange dye onto biochar adsorbent prepared from chicken manure.
In this work, the biochar adsorbent carboxymethyl cellulose (CMC), was prepared from the pyrolysis (600 °C, 120 min) of chicken manure for the removal of methyl orange (MO) from aqueous solution, and its physicochemical properties were characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectra (FTIR). The experimental parameters including agitation speed, initial solution pH, biochar dosage and contact time on the adsorption properties of MO from aqueous solution onto CMC were investigated in batch experiments. The kinetic adsorption of different initial concentration could be accurately described by the pseudo-second-order model and the overall rate process was apparently influenced by external mass transfer and intra-particle diffusion. Furthermore, the Langmuir isotherm model showed a better fit with equilibrium data (R2 > 0.99), with the maximum adsorption capacity of 39.47 mg·g-1 at 25 °C. Moreover, the thermodynamic parameters indicated that the adsorption of MO onto CMC was a spontaneous and endothermic process. The results of this study indicated that CMC could be used as a promising biomass adsorbent material for aqueous solutions containing MO.


Characterization of the sigmaE-dependent rpoEp3 promoter of Salmonella enterica serovar Typhimurium.
Using a two-plasmid system, we recently identified sigma(E)-dependent promoters directing expression of the sigma(E) regulon genes in Salmonella enterica serovar Typhimurium (S. Typhimurium). Comparison of the promoters revealed a consensus sequence almost identical to the sigma(E)-dependent rpoEp3 promoter directing expression of rpoE. This two-plasmid system was previously optimized to identify nucleotides critical for the rpoEp3 promoter activity. However, two highly conserved nucleotides in the sigma(E) consensus sequence were not identified by this screening. In the present study, we have improved the two-plasmid screening system using a new optimized error-prone PCR mutagenesis. Together with site-directed mutagenesis, we further identified nucleotides critical for activity of the rpoEp3 promoter and quantified the effect of the particular mutation upon promoter activity. All the identified critical nucleotides of the rpoEp3 promoter (in capital) were located in the -35 (ggAACtt) and -10 (gTCtaA) regions and corresponded to the most conserved nucleotides in the sigma(E) consensus sequence. The expression of the wild-type and mutated rpoEp3 promoters was confirmed in S. Typhimurium and was found to exhibit a different pattern of sigma(E) activation compared with Escherichia coli, with a peak rpoEp3 promoter activity in early stationary phase followed by a decrease in late stationary phase.


Silicon nanowire ion sensitive field effect transistor with integrated Ag/AgCl electrode: pH sensing and noise characteristics.
We have fabricated Si nanowire (SiNW) based ion-sensitive field effect transistors (ISFETs) for biosensing applications. The ability to prepare a large number of sensors on a wafer, the use of standard silicon microfabrication techniques resulting in cost savings, and potential high sensitivity are significant advantages in favor of nanoscale SiNW ISFETs. The SiNW ISFETs with embedded Ag/AgCl reference electrode were fabricated on a standard silicon-on-insulator wafer using electron-beam lithography and conventional semiconductor processing technology. The current-voltage characteristics show an n-type FET behavior with a relatively high on/off current ratio, reasonable sub-threshold swing value, and low gate-leakage current. The pH responses of the ISFETs with different pH solutions were characterized at room temperature which showed a clear lateral shift of the drain current vs. gate voltage curve with a change in the pH value of the solution and a sensitivity of 40 mV pH(-1). The low frequency noise characteristics were investigated to evaluate the signal to noise ratio and sensing limit of the devices.


Evaluation of macrocytosis.
Macrocytosis, generally defined as a mean corpuscular volume greater than 100 fL, is frequently encountered when a complete blood count is performed. The most common etiologies are alcoholism, vitamin B12 and folate deficiencies, and medications. History and physical examination, vitamin B12 level, reticulocyte count, and a peripheral smear are helpful in delineating the underlying cause of macrocytosis. When the peripheral smear indicates megaloblastic anemia (demonstrated by macro-ovalocytes and hyper-segmented neutrophils), vitamin B12 or folate deficiency is the most likely cause. When the peripheral smear is non-megaloblastic, the reticulocyte count helps differentiate between drug or alcohol toxicity and hemolysis or hemorrhage. Of other possible etiologies, hypothyroidism, liver disease, and primary bone marrow dysplasias (including myelodysplasia and myeloproliferative disorders) are some of the more common causes.


Organoid-Derived Epithelial Monolayer: A Clinically Relevant In Vitro Model for Intestinal Barrier Function.
In the past, intestinal epithelial model systems were limited to transformed cell lines and primary tissue. These model systems have inherent limitations as the former do not faithfully represent original tissue physiology, and the availability of the latter is limited. Hence, their application hampers fundamental and drug development research. Adult stem-cell-based organoids (henceforth referred to as organoids) are miniatures of normal or diseased epithelial tissue from which they are derived. They can be established very efficiently from different gastrointestinal (GI) tract regions, have long-term expandability, and simulate tissue- and patient-specific responses to treatments in vitro. Here, the establishment of intestinal organoid-derived epithelial monolayers has been demonstrated along with methods to measure epithelial barrier integrity, permeability and transport, antimicrobial protein secretion, as well as histology. Moreover, intestinal organoid-derived monolayers can be enriched with proliferating stem and transit-amplifying cells as well as with key differentiated epithelial cells. Therefore, they represent a model system that can be tailored to study the effects of compounds on target cells and their mode of action. Although organoid cultures are technically more demanding than cell lines, once established, they can reduce failures in the later stages of drug development as they truly represent in vivo epithelium complexity and interpatient heterogeneity.


Electrochemical synthesis of novel 1,3-indandione derivatives and evaluation of their antiplatelet aggregation activities.
Electrochemical oxidation of some selected catechol derivatives, using cyclic voltammetry, in the presence of different 2-aryl-1,3-indandiones as nucleophiles, resulted in electrochemical synthesis of new 1,3- indandione derivatives in an undivided cell in good yield and purity. A Michael addition mechanism was proposed for the formation of the analogs based on the reaction conditions which were provided in electrochemical cell. The in-vitro antiplatelet and anticoagulant activity of these compounds was evaluated, using arachidonic acid (AA) and adenosine diphosphate (ADP) as the platelet aggregation inducers. The results show that the incorporation of catechol ring in 1,3-indandione nucleus leads to the emergence of antiplatelet aggregation activity in these compounds. The compounds may exert their antiaggregation activity by interfering with the arachidonic acid pathway.


Assessment of left ventricular function and peripheral vascular arterial stiffness in patients with dipper and non-dipper hypertension.
A non-dipper pattern of high blood pressure is associated with increased risk of organ damage and cardiovascular disease in patients with hypertension. The aim of the study was to evaluate the left ventricular (LV) remodeling and function and arterial stiffness in a dipper/non-dipper pattern of high blood pressure in patients with hypertension. A total of 183 hypertensive patients with no history of adverse cardiovascular events were divided into two groups based on 24 hours ambulatory blood pressure monitoring (ABPM): 66 patients with a dipper pattern and 117 patients with non-dipper pattern. Detailed transthoracic echocardiogram was performed and analyzed with advance speckle tracking 3-orthogonal direction strain analysis to assess LV systolic function and tissue Doppler-derived E/E' for LV diastolic function assessment. Cardio ankle vascular index (CAVI) was used to evaluate arterial stiffness. Compared with patients with dipper hypertension, those with non-dipper hypertension had increased LV mass index, higher prevalence of eccentric and concentric LV hypertrophy, more impaired LV diastolic and systolic function and peripheral arterial stiffness. Multivariable analysis revealed that a non-dipper pattern was independently associated with LV systolic dysfunction evaluated by speckle tracking-derived strain analysis. In conclusion, a non-dipper pattern of hypertension is an independent risk factor for LV systolic dysfunction. Treatment that could reverse this non-dipper pattern may reduce cardiac damage in these patients.


Cross-cultural adaptation of Dimensions of Corporate Safety Scorecard to the Brazilian Portuguese language.
A broad-scoped approach to the assessment, documentation and application of health inputs at the workplace is needed to perform effective interventions, reduce occupational hazards and promote workers' health and safety. Effective efforts might thus be organized into programs and initiatives to preserve and improve the health and safety of workers. To perform the translation and cross-cultural adaptation of the Dimensions of Corporate Safety Scorecard for use in Brazil to broaden the scope of means to approach and measure the effectiveness of workplace safety actions. The translation and cultural adaptation of the Dimensions of Corporate Safety Scorecard followed recommendations applied in similar studies which establish six steps: foreword translation, reconciliation, back translation, review by internal committee, cultural evaluation of the translation by an external expert panel (pretest) and final review. Adoption of the described procedure enabled a detailed analysis of possible options in case of divergences in statements between versions. Thus the quality of the results was ensured and the semantic qualities of the original version were preserved in the translation. The Brazilian Portuguese version of Dimensions of Corporate Safety Scorecard, entitled "Questionário sobre Dimensões da Segurança Corporativa," obtained in the present study represents the first step in the use of this instrument for measurement of the effectiveness of health, safety and well-being actions in different work environments.


Real-time fast physical random number generator with a photonic integrated circuit.
Random number generators are essential for applications in information security and numerical simulations. Most optical-chaos-based random number generators produce random bit sequences by offline post-processing with large optical components. We demonstrate a real-time hardware implementation of a fast physical random number generator with a photonic integrated circuit and a field programmable gate array (FPGA) electronic board. We generate 1-Tbit random bit sequences and evaluate their statistical randomness using NIST Special Publication 800-22 and TestU01. All of the BigCrush tests in TestU01 are passed using 410-Gbit random bit sequences. A maximum real-time generation rate of 21.1 Gb/s is achieved for random bit sequences in binary format stored in a computer, which can be directly used for applications involving secret keys in cryptography and random seeds in large-scale numerical simulations.