Enhancement of the photokilling effect of aluminum phthalocyanine in photodynamic therapy by conjugating with nitrogen-doped TiO2 nanoparticles.
As a second-generation photodynamic therapy (PDT) photosensitizer, aluminum phthalocyanine chloride tetrasulfonate (Pc) has gained great attention due to its high absorption at the red light region. Yet, its application in PDT is strongly limited by its low cellular uptake efficiency. In this report, nitrogen-doped TiO2 nanoparticles (N-TiO2) conjugated with Pc are synthesized by a two-step surface modification method. The N-TiO2-Pc products are characterized by Zeta potential, transmission electron microscopy and UV-vis absorption spectroscopy. The cellular uptake, intracellular distribution, cytotoxicity and the photokilling effect of the nanoparticles are studied on different cancer cell lines. Compared with Pc, the absorption spectrum of N-TiO2-Pc expands from red to UV region, resulting in a higher production of reactive oxygen species under visible light irradiation. In addition, the cellular uptake of Pc is largely improved by its carrier N-TiO2. The photokilling efficiency of N-TiO2-Pc is over ten times higher than that of Pc. The results suggest that N-TiO2-Pc is an excellent candidate as a photosensitizer in PDT.


Aortic Stenosis and Cardiac Amyloidosis: JACC Review Topic of the Week.
The prevalence of calcific aortic stenosis (AS) and of cardiac amyloidosis (CA) increases with age, and their association is not uncommon in the elderly. The identification of CA is particularly challenging in patients with AS because these 2 conditions share several features. It is estimated that ≤15% of the AS population and ≤30% of the subset with low-flow, low-gradient pattern may have CA. In patients with AS, CA is associated with increased risk of heart failure, mortality, and treatment futility with aortic valve replacement. In case of suspicion of CA, it is thus crucial to confirm the diagnosis to guide therapeutic management of AS and eventually implement recently developed pharmacological treatment dedicated to transthyretin amyloidosis. Given the high surgical risk of patients with AS and concomitant CA, transcatheter aortic valve replacement may be preferred to surgery in these patients.


Inhibition of oxygen utilization and destruction of ubiquinone by ultraviolet irradiation of Thiobacillus thiooxidans.
Ultraviolet (UV) irradiation inhibited sulfur oxidation by cells of Thiobacillus thiooxidans. Sulfur-oxidizing activity decreased as the exposure time to UV light increased. A loss of the ability of cells of fix CO(2) paralleled the loss of sulfur-oxidizing activity. UV light photoinactivated ubiquinone purified from T. thiooxidans. The same percentage of sulfur-oxidizing activity and ubiquinone was destroyed after 15 min of UV exposure. Both the photoinactivation of sulfur oxidation and ubiquinone followed first-order reaction kinetics. The specific rate constants for both photoinactivations were nearly equal. Cells completely inactivated by UV light contained no ubiquinone. Ubiquinone was found to be a component of the cell wall-membrane complex.


Relationship between Doppler pulsatility index and direct femoral pressure measurements in the diagnosis of aortoiliac occlusive disease.
One hundred and seventy-five aortofemoral segments were studied in order to determine the role of CW Doppler ultrasound combined with real-time spectral analysis in the assessment of aortoiliac disease. The pulsatility index (PI), determined from the maximum velocity waveform, was compared to the systolic pressure difference between the aorta and common-femoral artery as measured at the time of angiography. Receiver operating characteristic curves were constructed and the optimum sensitivities and specificities measured. Results show that if a PI(max) of 5.5 is taken as the threshold level, then the PI is 95% sensitive and specific in detecting hemodynamically significant aortoiliac disease that corresponds to a resting aortofemoral pressure difference of 10 mm Hg or greater. We also carefully examine those technical aspects of Doppler recording and analysis that influence the accuracy of PI measurements.


Impairments and compensation in string-pulling after middle cerebral artery occlusion in the rat.
Stroke is a leading cause of long-term disability in humans, and it is frequently associated with impairments in the skilled use of the arms and hands. Many human upper limb impairments and compensatory changes have been successfully modeled in rodent studies of neocortical stroke, especially those that evaluate single limb use in tasks, such as reaching for food. Humans also use their hands for bilaterally coordinated movements, dependent upon interhemispheric cortical projections, which are also compromised by unilateral stroke. This study describes middle cerebral artery occlusion (MCAO) dependent changes in the bilaterally dependent hand use behavior of string-pulling in the rat. The task involves making hand-over-hand movements to pull down a string that contains a food reward attached to its end. MCAO rats missed the string more often with both hands than Sham rats. When the string was missed on the contralateral to MCAO body side, rats continued to cycle through subcomponents of string-pulling behavior as if the string were grasped in the hand. Rats also failed to make a grasping motion with the contralateral to MCAO hand when the string was missed and instead, demonstrated an open-handed raking-like motions. Nevertheless, with repeated attempts, rats performed components of string-pulling well enough to obtain a reward on the end of the string. Thus, string-pulling behavior is sensitive to bilateral impairments but is achieved with compensatory adjustments following MCAO. These aspects of MCAO string-pulling provide a foundation for studies that investigate the efficacy of therapeutic intervention which might enhance neuroplasticity and recovery.


Detection of anomalous splenic artery aneurysms with three-dimensional contrast-enhanced MR angiography.
Aneurysms of the splenic artery which arise anomalously from the superior mesenteric artery are extremely rare but clinically important because of their life-threatening hemorrhage. Diagnostic imaging plays an important role in the diagnosis and conducting treatment strategy. The aim of this study was to evaluate the detection of anomalous splenic artery aneurysms with 3D contrast-enhanced MR angiography. 3D contrast-enhanced MR angiography was performed in six patients with anomalous splenic artery aneurysms. The mean diameter of six aneurysms was 3.9 cm. All of them were saccular and located at the origin of the splenic artery that arose anomalously from the root of the superior mesenteric artery. 3D contrast-enhanced MR angiography clearly demonstrated the aneurysm's location, size, morphology, visceral arterial variations, and was superior to DSA in three-dimensional display of the aneurysm and its relationship with surrounding vessels and organs. Two patients underwent open vascular surgery and three endovascular procedure. 3D contrast-enhanced MR angiography is a noninvasive and accurate technique for diagnosis of anomalous splenic artery aneurysms. Its 3D anatomic information is very helpful for treatment planning. It can be used as one of the first choice examinations for anomalous splenic artery aneurysms.


The effect of tunicamycin on transferrin synthesis and secretion in hormonally stimulated explants of rabbit mammary gland.
Pregnant rabbit mammary gland explants cultured with insulin, prolactin and cortisol synthesize and secrete transferrin radiolabelled with [3H]leucine or [3H]mannose. Addition of tunicamycin inhibits the glycosylation but not synthesis of the [3H]leucine-labelled polypeptide. Secretion of the non-glycosylated protein is only marginally inhibited.


[Qualified post-mortem examination-experiences from Bremen].
On 1 August 2017, the qualified post-mortem examination was introduced in Bremen by changing the relevant law. A substantial change is the separation of the pure death determination, which can be done by any physician, and the subsequent execution of the post-mortem examination by a suitably qualified physician. For the city of Bremen, the Institute for Legal Medicine (IRM) was charged with this task (in Bremerhaven, the health department).In this article, practical implementation, problems, and advantages and disadvantages of the new law are presented. For the year 2018 we did a statistical evaluation of the qualified post-mortem examination.After notification of a case of death to the IRM, the post-mortem examination will be carried out on the same or the following working day by an IRM doctor. In 2018, 7585 post-mortem examinations took place. In nearly 300 cases (4%) the type of death had to be changed (natural/not natural).Problems arise if external undertakers are involved. Further challenges arise in the collection of the anamnesis and implementation after extended weekends as well as due to the lack of knowledge about the death scene and generally the difficulty to conclude on the cause of death within the scope of an external post-mortem examination. One advantage to mention is that every deceased person is relatively promptly subjected to a post-mortem examination by a qualified doctor and overall the quality of the examination has improved. A disadvantage is the increased cost.


Integrating spatial data and shorebird nesting locations to predict the potential future impact of global warming on coastal habitats: A case study on Farasan Islands, Saudi Arabia.
One of the expected effects of the global warming is changing coastal habitats by accelerating the rate of sea level rise. Coastal habitats support large number of marine and wetland species including shorebirds (plovers, sandpipers and allies). In this study, we investigate how coastal habitats may be impacted by sea level rise in the Farasan Islands, Kingdom of Saudi Arabia. We use Kentish plover Charadrius alexandrinus - a common coastal breeding shorebird - as an ecological model species to predict the influence of sea level rise. We found that any rise of sea level is likely to inundate 11% of Kentish plover nests. In addition, 5% of the coastal areas of Farasan Islands, which support 26% of Kentish plover nests, will be flooded, if sea level rises by one metre. Our results are constrained by the availability of data on both elevation and bird populations. Therefore, we recommend follow-up studies to model the impacts of sea level rise using different elevation scenarios, and the establishment of a monitoring programme for breeding shorebirds and seabirds in Farasan Islands to assess the impact of climate change on their populations.


Long-term potentiation and depression in the intermediate gray matter of rat spinal cord in vitro.
Field potentials recorded from a group of cells in the intermediomedial gray matter of spinal cord slices from neonatal rats showed long-term potentiation and long-term depression in response to brief bursts of high frequency conditioning stimulation. Both N-methyl-D-aspartic acid-dependent and N-methyl-D-aspartic acid-independent long-term potentiation was seen. The long-term depression was partially reversed, but not prevented from occurring, by the opiate antagonist naloxone. The frequency of occurrence of long-term potentiation and depression was affected by the inhibitory blockers bicuculline and strychnine in a fashion consistent with the hypothesis that a slight depolarization favoured long-term potentiation and a larger depolarization favoured long-term depression.


Time-resolved fluoroimmunoassay for bactericidal/permeability-increasing protein.
Bactericidal/permeability-increasing protein (BPI) is a cationic antimicrobial protein produced by polymorphonuclear leukocytes, that specifically interacts with and kills Gram-negative bacteria. BPl competes with lipopolysaccharide-binding protein (LBP) secreted by liver cells into blood plasma for binding to lipopolysaccharide (LPS) and thus reduces the proinflammatory effects of LPS. We have developed a time-resolved fluoroimmunoassay for BPI and measured the concentration of BPI in human serum and plasma samples. The assay is based on a rabbit antibody against recombinant BPI. This antibody specifically adheres to polymorphonuclear leukocytes in immunostained human tissues. The difference in the serum concentration of BPI between unselected hospitalized patients with and without an infection was statistically significant. The mean concentration of BPI in serum samples was 28.3 mug/l (range 1.64-132, S.D. 26.8, n = 83). In contrast, there was no difference between the two groups in the BPI levels in plasma samples. For all individuals tested, BPI levels were consistently higher in plasma samples compared to the matched serum samples. The mean concentration of BPI in plasma samples was 52.3 mug/l (range 0.9-403, S.D. 60.6, n = 90). There was a positive correlation between the concentration of BPI and the white blood cell count as well as between the BPI concentration and C-reactive protein (CRP) in serum samples. In conclusion, the present study demonstrates that BPI can be quantified reliably by time-resolved fluoroimmunoassay in human serum samples.


Brefeldin A-regulated retrograde transport into the endoplasmic reticulum of internalised wheat germ agglutinin.
The effects of the fungal metabolite brefeldin A (BFA) on the endocytic routes of internalised wheat germ agglutinin (WGA) were studied in human HepG2 hepatoma cells, drawing particular attention to the application times in relation to the membrane dynamics occurring at the trans Golgi face during endocytosis. As shown in previous studies, transport of internalised WGA into the Golgi apparatus can be classified in three stages being characterised by predominance of vesicular endosomes (stage I), formation of an extended endocytic trans Golgi network (stage II) and uptake of WGA into the stacked Golgi cisternae (stage III). BFA treatment of the cells led to rapid tubular-reticular transformations of the Golgi stacks. Retrograde transport and further destinations of internalised WGA depended on the time of BFA application. When BFA was administered during stages I or II, WGA was localised within the BFA-induced tubules and networks, but never was found within the endoplasmic reticulum. By contrast, BFA treatment during stage III led to a redistribution of internalised WGA into cisternae of the endoplasmic reticulum. These results show that BFA administered according to a precise time schedule can be used as a regulatory agent that allows to control retrograde traffic of internalised molecules into the endoplasmic reticulum.


Modified Group Contribution Scheme to Predict the Glass-Transition Temperature of Homopolymers through a Limiting Property Dataset.
Previous studies on glass-transition temperature (T g) prediction mainly focus on developing diverse methods with higher regression accuracy, but very little attention has been paid to the dataset. Generally, a large range of T g values of a specified polymer could be found in the literature but which one should be selected into a dataset merely depends on the implicit preference rather than a recognized and clear criterion. In this paper, limiting glass-transition temperature (T g(∞)), a constant value obtained at the infinite number-average molecular weight M n, was validated to be an adequate bridge index in the T g prediction models. Furthermore, a new dataset containing 198 polymers was established to predict T g(∞) using the improved group contribution method and it showed a good correlation (R 2 = 0.9925, adjusted R 2 = 0.9894). The method could also generate T g-M n curves by introducing the T g(∞) function and provide more information to polymer scientists and engineers for material selection, product design, and synthesis.


Specific microRNAs as novel biomarkers for combination chemotherapy resistance detection of colon adenocarcinoma.
Colon cancer is a frequently occurring primary malignant tumor. Chemotherapy can reduce the risk of local and distant relapse. Therefore, it is very important to find new biomarkers that can predict chemoresistance and help in individuate treatment decision. Retrospective analysis of 126 patients, who were treated at our department between June 2010 and December 2014. In this study, we examined the expression levels of 1200 human miRNAs in colon cancer tissues, using laser capture microdissection and microRNA profiling arrays. A validation study was done to corroborate a subset of the results, including expression levels of miR-4299, miR-196b, miR-324-5p, miR-455-3p and miR-939, through analyzing stage IV colon adenocarcinoma tissues (not responding and responding to the chemotherapy) with laser capture microdissection and quantitative real-time PCR. We analyze the relationship between the expression levels of these miRNAs and the survival rate of colon cancer patients by Kaplan-Meier method. We found that miR-4299 and -196b have significant diagnostic value in chemoresistant colon cancer. MiR-4299 yielded an AUC (the areas under the ROC curve) of 0.810 and miR-196b yielded an AUC of 0.726 in discriminating chemoresistant colon cancer from controls. Combined with ROC analyses of these 2 miRNAs revealed an elevated AUC of 0.877 with 71.4 % sensitivity and 95.5 % specificity in discriminating chemoresistant colon cancer. The low level of miR-4299 expression and the high level of -196b expression are significantly correlated with better survival of colon cancer patients. These data suggest that miR-4299 and -196b have strong potential as novel biomarkers for chemoresistance detection of colon cancer.


[The value of sialography (evaluation of 251 cases) (author's transl)].
Sialography is of value for showing opaque or nonopaque stones in the maxillary glands. Possible complications (inflammation, abscess and fistula) can also be shown. Acute and chronic inflammation and sialadenoses show typical pictures. The diagnosis of tumors is less certain, genignity or malignity cannot be determined.


Mucocutaneous Diseases.
Mucocutaneous diseases affecting the oral cavity are predominantly immune mediated or inflammatory. Three of the most common and clinically significant conditions are reviewed in this article: lichen planus, pemphigus vulgaris, and mucous membrane pemphigoid. Because oral manifestations may be the first or only manifestation of mucocutaneous diseases, oral health professionals play a critical role in the early diagnosis and multidisciplinary management of these conditions.


Malnutrition and behavior.
Severe malnutrition during the fetal or infancy period in animals and humans decreases brain size, reduces the number of brain cells, and results in behavioral abnormalities. The relationship between lesser degrees of malnutrition and intellectual development is more complex. Social, genetic, and other factors assume greater roles under the latter conditions. Before we can draw firm conclusions that malnutrition per se is the cause of mental subnormality, we must complete analyses from on-going longitudinal studies in order to clarify the role of parental interaction with malnourished child and of the social environmental factors which accompany malnutrition.


Social determinants of perinatal mental health during the COVID-19 pandemic.
We sought to clarify relevant social-structural determinants of perinatal mental health-material and social resources, as well as pandemic employment-related stressors, in White and BIPOC child-bearers-toward building comprehensive risk screening and prevention/intervention models that can alleviate health disparities. Each of these determinants was hypothesized to contribute to perinatal symptoms in ways that disproportionately benefit White child-bearers. A community sample of Illinois child-bearers (n = 409 pregnant, 122 new parents) completed online questionnaires from May 2020-June 2021. Relations between composite measures of child-bearers' material resources, social resources, and pandemic employment-related stressors and mental health symptoms were tested in multiple regression models. Main effects of social determinant composites and moderated effects by race/ethnic identification were tested. All social determinants displayed significant unique associations with mental health in the sample, with social resources carrying the greatest weight. Although no moderated effects of composite resource measures were found, the relation between pandemic employment-related reduced resources and symptoms proved stronger in BIPOC compared to White child-bearers. Both stable social-structural determinants and acute crisis-related shifts contribute to perinatal mental health, with higher levels and/or impacts of resources helping to explain racial/ethnic disparities. These findings can inform more comprehensive screening and prevention protocols and policy recommendations that improve perinatal health outcomes.


Poor response rate to a continuous schedule of Amifostine therapy for 'low/intermediate risk' myelodysplastic patients.
Ineffective haemopoiesis leading to cytopenia presents the major clinical management problem for patients with myelodysplasia (MDS). Preliminary studies have demonstrated that the synthetic aminothiol Amifostine stimulates multilineage haemopoiesis both in vitro and in vivo in patients with MDS. We have treated 12 patients with an uninterrupted 8-week schedule of thrice-weekly intravenous Amifostine with a starting dose of 300 mg/m2 escalating to 450 mg/m2 in non-responders. No patients satisfied response criteria on study but two patients showed minor responses. We conclude that therapeutic response to Amifostine in MDS may be schedule dependent.


Efficiency and safety of surgical intervention to patients with Non-Cystic Fibrosis bronchiectasis: a meta-analysis.
No quantitative systematic review was found to report the efficiency and safety of surgical resection in the management of non-cystic fibrosis (non-CF) bronchiectasis. We therefore conducted a meta-analysis to assess the effects of operative intervention to patients with non-CF bronchiectasis. PubMed, the Cochrane library and Web of Science databases were searched up to July 8th, 2015. The pooled mortality from 34 studies recruiting 4788 patients was 1.5% (95% CI, 0.9-2.5%). The pooled morbidity from 33 studies consisting of 4583 patients was 16.7% (95% CI, 14.8-18.6%). The pooled proportion of patients from 35 studies, consisting of 4614 patients who were free of symptoms was 66.5% (95% CI, 61.3-71.7%) after surgery. The summary proportion of patients from 35 articles including 4279 participants who were improved was 27.5% (95% CI, 22.5-32.5%), and 9.1% (95% CI, 7.3-11.5%) showed no clinical improvement. In conclusion, our analysis indicated that lung resection in the management of non-CF bronchiectasis is associated with significant improvements in symptoms, low risk of mortality and acceptable morbidity.


Trafficking to the plasma membrane of the seven-transmembrane protein encoded by human herpesvirus 6 U51 gene involves a cell-specific function present in T lymphocytes.
The sequence of human herpesvirus 6 (HHV-6) U51 open reading frame predicts a protein of 301 amino acid residues with seven transmembrane domains. To identify and characterize U51, we derived antipeptide polyclonal antibodies and developed a transient expression assay. We ascertained that U51 was synthesized in cord blood mononuclear cells infected with either variant A- or variant B-HHV-6 and was transported to the surface of productively infected cells. When synthesized in transient expression systems, U51 intracellular trafficking was regulated in a cell-type-dependent fashion. In human monolayer HEK-293 and 143tk- cells, U51 accumulated predominantly in the endoplasmic reticulum and failed to be transported to the cell surface. In contrast, in T-lymphocytic cell lines J-Jhan, Molt-3, and Jurkat, U51 was successfully transported to the plasma membrane. We infer that transport of U51 to the cell surface requires a cell-specific function present in activated T lymphocytes and T-cell lines.


The incidence of post-traumatic stress disorder among survivors after earthquakes:a systematic review and meta-analysis.
Post-traumatic stress disorder (PTSD) is a common psychological disorder caused by unusual threats or catastrophic events. Little is known about the combined incidence of PTSD after earthquakes. This study aimed at evaluating the combined incidence of PTSD among survivors after earthquakes using systematic review and meta-analysis. The electronic databases of PubMed, Embase, Web of Science and PsycARTICLES were searched for relevant articles in this study. Loney criteria were used to assess the quality of eligible articles. The combined incidence of PTSD was estimated by using the Freeman-Tukey double arcsine transformation method. Subgroup analyses were conducted using the following variables: the time of PTSD assessment, gender, educational level, marital status, damage to one's house, bereavement, injury of body and witnessing death. Forty-six eligible articles containing 76,101 earthquake survivors met the inclusion criteria, of which 17,706 were diagnosed as having PTSD. Using a random effects model, the combined incidence of PTSD after earthquakes was 23.66 %. Moreover, the combined incidence of PTSD among survivors who were diagnosed at not more than 9 months after earthquake was 28.76 %, while for survivors who were diagnosed at over nine months after earthquake the combined incidence was 19.48 %. A high degree of heterogeneity (I(2) = 99.5 %, p<0.001) was observed in the results, with incidence ranging from 1.20 to 82.64 %. The subgroup analyses showed that the incidence of PTSD after earthquake varied significantly across studies in relation to the time of PTSD assessment, gender, educational level, damage to one's house, bereavement, injury of body and witnessing death. However, stratified analyses could not entirely explain the heterogeneity in the results. Given the high heterogeneity observed in this study, future studies should aim at exploring more possible risk factors for PTSD after earthquakes, especially genetic factors. In spite of that, the results of this study suggest that nearly 1 in 4 earthquake survivors are diagnosed as having PTSD. Therefore, the local government should plan effective psychological interventions for earthquake survivors.


Microinjection in combination with microfluorimetry to study proton diffusion along phospholipid membranes.
Proton diffusion along the surface of a planar bilayer lipid membrane was measured by means of acid/base injection with a micropipette and recording of the kinetics of fluorescence changes of fluorescein-labelled lipid on the surface. The dimensionality of the process was assayed by fitting the kinetic curves with two-dimensional (2D) or three-dimensional (3D) diffusion equations. In agreement with Serowy et al. (Biophys J 84:1031-1037, 2003), lateral proton diffusion proceeded via bulk phase by means of buffer molecules as proton carriers (D = 600 microm2/s) under the conditions of 1 mM buffer in the solution. Introduction of proton binding sites on the membrane surface led to the appearance of a considerable contribution of two-dimensional proton diffusion on the membrane surface with D = 1,100 mum(2)/s. The system described can be used to study the dependence of the proton diffusion rate on the phospholipid and protein composition of the membrane.


Involvement of CCAAT/enhancer binding protein-beta (C/EBPbeta) in epigenetic regulation of mouse methionine adenosyltransferase 1A gene expression.
Methionine adenosyltransferase (MAT) catalyzes the synthesis of S-adenosylmethionine, the main methyl donor in cellular transmethylation reactions and the aminopropyl moiety in polyamine biosynthesis. In mammals, two different genes, MAT1A and MAT2A, encode catalytic polypeptides of liver-specific MAT I/III and ubiquitous MAT II, respectively. Reverse transcription-polymerase chain reaction showed that MAT1A gene expression was at a detectable level in embryonic day 14 mouse fetal liver and subsequently increased. Bisulfite genomic sequencing indicated that the methylation status of 10CpG sites in the MAT1A promoter proximal region was appreciably correlated with the gene expression in mouse developing liver and in adult hepatic cells; hepatic stellate cells and hepatocytes. When mouse hepatoma-derived Hepa-1 cells showing extremely low expression of MAT1A gene were treated with 5-aza-2'-deoxycytidine and trichostatin A, MAT1A gene expression was enhanced. In addition, in vitro methylation of the MAT1A promoter region suppressed the MAT1A promoter activity in reporter assay. Next, we performed electrophoretic mobility shift assay and found that the transcriptional factor CCAAT/enhancer binding protein-beta (C/EBPbeta) specifically binds to a putative binding site of C/EBPbeta in the MAT1A promoter. Suppression of C/EBPbeta expression by short hairpin RNA decreased the MAT1A promoter activity and MAT1A gene expression, and inhibition of C/EBPbeta binding to MAT1A by site-directed mutagenesis also showed similar results. Western blot analysis and chromatin immunoprecipitation assay indicated that C/EBPbeta binding is dependent on DNA methylation status. Based on these findings, we conclude that C/EBPbeta plays an important role in epigenetic regulation of the mature hepatic gene MAT1A.


Infants attend to second-order relational properties of faces.
Two experiments investigated whether 7-month-old infants attend to the spatial distance measurements relating internal features of the human face. A visual preference paradigm was used, in which two versions of the same female face (one either lengthened or shortened, and one nonmodified) were presented simultaneously. In Experiment 1, infants looked longer at the nonmodified faces, which were determined to match the average distance relationships found in a sample of faces drawn from the same population. Longer looking times for modified faces were found in Experiment 2, in which the nonmodified faces were unusually long and the modified faces conformed to average distance measurements. It is proposed that infants' attention to the spatial relations of internal face features is an optimal tool for lifelong face recognition.


PREOPERATIVE DOMED MACULAR CONTOUR CORRELATES WITH POSTOPERATIVE VISUAL GAIN AFTER VITRECTOMY FOR SYMPTOMATIC EPIRETINAL MEMBRANE.
Evaluate macular features on preoperative ocular coherence tomography as indicators of postoperative visual gain following vitrectomy for epiretinal membrane (ERM). A retrospective chart review of 66 eyes that underwent vitrectomy with membrane and internal limiting membrane peeling for symptomatic ERM. Inclusion criteria required a pre-op visual acuity of at least 20/200 and minimum follow-up of 1 year. In addition, 31 of these eyes with complete 5-line raster pre-op ocular coherence tomography had segmentation analysis which included noncentral ERM to inner nuclear layer and ERM to outer plexiform layer measurements. Eyes with "domed" pre-op macular contour had a mean preoperative acuity of 20/70 and gained a mean 2.4 lines at one year, compared with those with "flat" or "depressed" macular contour, having a 20/60 mean preoperative acuity and 0.6 lines gained (P = 0.02). Changes for other ocular coherence tomography features examined were not statistically significant. Paracentral ERM to inner nuclear layer measurements had moderate correlation, whereas paracentral ERM to outer plexiform layer measurements had weak correlation with gain in visual acuity. An inner macular-domed contour in eyes with ERM predicted better visual gain after vitrectomy with ERM and internal limiting membrane peeling compared with a flat or depressed contour.


Weight gain in type 2 diabetes mellitus--not all uphill.
The goal of this study, of type 2 diabetes mellitus patients, treated in a referral community setting, was to follow the history of weight changes, in relation to the changing treatment modalities, and to detect independent risk factor and predictors for weight gain. 366 outpatients with type 2 diabetes (T2DM) were followed longitudinally for at least 5 years. 310 patients were treated with oral hypoglycemic agents and 56 patients had insulin treatment added to the oral therapy. The two groups did no differ significantly in the duration of diabetes, age of onset and admission HbA1c. The mean weight at admission was 78.9+/-15.1 and 76.7+/-15.0 kg (ns) respectively. No significant weight changes were noted on initiation of oral treatment and at final visit. The commencing of insulin therapy was the only step associated with a significant 3.7 kg increase in body weight (p<0.001) with a significant reduction in HbA1c (-1.4%, p<0.001). These changes however, followed a decrease in body weight that preceded insulin therapy. Mean weight at follow-up did not exceed the self-reported weight prior to the diagnosis of diabetes. The results show that weight gain does not necessarily accompany treatment of T2DM. Insulin therapy in T2DM is associated with some weight gain, mostly due to correction of glycemia and improvement of weight loss prior to insulin treatment. This should encourage the timely addition and combining of appropriate therapeutic modalities in order to achieve good glycemic control.


The geriatric mania asenapine study (GeMS).
Population aging results in growing numbers of psychiatric disorders among older patients. Yet, there is a paucity of studies on elderly mania. To evaluate the effect of asenapine on older manic inpatients. Thirty-four elderly patients suffering from a manic episode, mean age 67.2 years were enrolled in an open-label 3-weeks study of asenapine treatment. (1) DSM-IV criteria for manic episode (2) age above 60 years, (3) episode severity necessitating inpatient treatment, (4) Young Mania Rating Scale (YMRS) score at baseline >20, and (5) no prior asenapine treatment. Participants were prescribed asenapine 5 mg BID for 3 days and then dose increased to 10 mg BID till day 21 (study completion). Twenty-five patients completed the study. YMRS score decreased from a baseline mean of 27.0±8.8 to 13.3±12.0 at the end of the study (p<0.001). Fourteen patients (56% of completers) achieved remission (YMRS score<12). MADRS score decreased from a baseline mean of 7.6±5.6 to 4.4+5.1 at the end of the study (p<0.05); low baseline score should be noted. Sleep duration increased from a baseline median of 5.7 hours to 7.0 h at the end of the study (p<0.05). Seven patients discontinued treatment due to adverse events. Two patients passed-away after study completion. We tentatively conclude that the efficacy of asenapine in reducing acute manic symptoms and achieving remission in the elderly is supported in this study. Caution is needed in patients with co-morbid physical conditions.


Long-term use of clobazam in Lennox-Gastaut syndrome: experience in a single tertiary epilepsy center.
Clobazam (CLB) is a 1,5-benzodiazepine, which is known to be effective for treating refractory partial epilepsy. We have evaluated the long-term efficacy and tolerability of CLB as an add-on therapy in patients with Lennox-Gastaut syndrome (LGS). Forty-six patients with LGS who had received CLB add-on therapy were enrolled in this study. We retrospectively reviewed their clinical characteristics, including type of seizures, use of CLB, efficacy, adverse events, and retention rate. The mean±SD dose of CLB was 0.70±0.37 mg/kg per day (range, 0.16-1.60 mg/kg per day). After 1 month on CLB, 15 patients (32.6%) became seizure-free and 10 patients (21.7%) had 50% or greater seizure reduction. Response to CLB was not significantly associated with age, sex, or etiology (symptomatic or not). Five (10.8%) of 46 patients maintained seizure remission for more than 12 months. Tolerance developed in 48.0% of initial responders, and the 3-year retention rate by the Kaplan-Meier method was 76.6%. Seven patients (15.2%) reported adverse events, including somnolence and behavioral change, but only one discontinued CLB. Clobazam add-on therapy was effective and very tolerable in patients with LGS.


Reduced benzo-a-pyrene activation potential in lymphocytes from chronic alcoholics.
The effect of chronic ethanol consumption on the cellular metabolism of benzo-a-pyrene (BaP) is investigated in human peripheral lymphocytes obtained from 6 proven alcoholic addicts and 5 healthy donors. Lymphocytes convert BaP to dihydrodiols, diol-epoxides, phenols, quinone derivatives and polyhydroxylated forms. Sulfate, glucuronide and glutathione conjugates are also detected. The average production of metabolites is much lower in lymphocytes of alcoholics and a net global decrease of "active" metabolite production, i.e., diols and BPDE, is also observed. In contrast, conjugated metabolites are formed in increased amounts. The data indicate that the metabolism of BaP in lymphocytes from chronic alcoholics is characterized essentially by a lowered rate of metabolized BaP and a reduction of their BaP activation potential, as seen by the increased production of conjugated metabolites and the markedly decreased protein-bound active mutagen.


Telework and MaaS adoption in a post-pandemic scenario. Evidence from municipal employees of Padua, Italy.
In recent years, the adoption of teleworking has witnessed a significant surge, partly driven by the COVID-19 pandemic. The existing literature suggests that its implementation has elicited mixed reactions from workers; while some workers have expressed satisfaction with its introduction, others prefer to work in a traditional, on-site setting. Concurrently, there has been a growing interest in Mobility-as-a-Service (MaaS) and an increase in the number of companies offering such services. However, there is limited research exploring the relationship between teleworking and the utilization of MaaS. This paper aims to fill this gap, by analyzing (1) which factors influence users to adopt teleworking in a post-pandemic scenario and (2) the relationship between willingness to telework and the propensity to join a MaaS system. An ordered logit model and a mixed logit model were developed to achieve the two goals, respectively. These models were calibrated and validated using data collected from questionnaires administered to Padua Municipality employees between October 2020 and January 2021. As expected, the employees most inclined toward teleworking are those who seek more flexibility and are unable to commute by private means. In addition, results show that employees who expressed the preference to telework more in the future are less likely to adopt MaaS, suggesting that the increased popularity of teleworking due to the pandemic may have a negative effect on the uptake of MaaS. These findings were utilized to formulate several policy recommendations.


Effect of ingestion of eicosapentaenoic acid ethyl ester on carrageenan-induced colitis in guinea pigs.
The effect of highly purified eicosapentaenoic acid ethyl ester (EPA-E) on colitis was investigated using a guinea pig model. The technique for preparing a degraded carrageenan with a molecular weight of about 30,000 from commercial iota-carrageenan was first refined. When this degraded carrageenan was fed to guinea pigs, localized ulcerations occurred in the cecum with infiltration of numerous mononuclear phagocytes. Oral administration of 300 mg.kg-1.day-1 of EPA-E for 3 weeks significantly prevented the development of colitis. The amounts of prostaglandin E2, thromboxane B2, and leukotriene B4 released from the cecal mucosa were also measured. The release of prostaglandin E2 and thromboxane B2 was significantly decreased in the animals fed EPA-E compared with those given olive oil or a vehicle alone. In addition, there was a positive correlation between the amounts of these eicosanoids and the degree of ulcer formation. However, there was no difference in the amount of leukotriene B4 among various experimental groups of animals. Furthermore, EPA-E feeding induced a significant decrease in the level of arachidonic acid and a significant increase in that of EPA in peritoneal macrophages. These results suggest that EPA has a prophylactic effect on the development of carrageenan-induced colitis, which may be ascribed in part to reduced eicosanoid production.


Distinctive roles of L-type calcium channels subtypes within the dorsal hippocampus in formation of morphine withdrawal-induced aversion in rats.
Although the negative effects coming along with opiate withdrawal are in part modulated by L-type calcium channels (LTCCs), the distinctive physiological properties and functions of LTCCs subtypes suggest differential roles of subtypes during withdrawal. The present study aimed to examine the contributions of LTCC subtypes, Cav1.2 and Cav1.3, within the dorsal hippocampus (DH) in naloxone-precipitated morphine withdrawal using the conditioned place aversion (CPA) paradigm. Firstly, we injected the non-specific LTCCs antagonist verapamil into the DH of morphine-dependent rats before conditioning an environment with naloxone-precipitated withdrawal. Our results showed that verapamil blocked the acquisition of CPA. Then, to explore the molecular mechanisms of LTCCs subtypes during withdrawal, we measured the protein expression of Cav1.2 and Cav1.3 in morphine-dependent rats under different conditions. In morphine-dependent rats, conditioning with withdrawal increased Cav1.2 expression in the membrane, while only acute naloxone injection increased the membrane expression of Cav1.3. To further determine the causal roles of LTCCs subtypes in the withdrawal process, we used Cav1.2 siRNA or Cav1.3 shRNA to knock down the expression of subtypes and detected the effects on CPA and somatic withdrawal signs in morphine-dependent rats. Cav1.2 siRNA, but not Cav1.3 shRNA, inhibited the acquirement of CPA and relieved somatic withdrawal symptoms. Together, our findings reveal that Cav1.2, but not Cav1.3 plays an important role in mediating morphine withdrawal, suggesting this subtype may serve as a potential therapeutic target for the treatment of negative effects in opiate dependence.


Studies of an alpha-fetoprotein assay using dry blood-spot samples to be used for the detection of fetal neural tube defects.
We modified the Pharmacia serum alpha-fetoprotein (AFP) kit to enable its use with dry blood-spots on filter paper. Reference values were established for blood from 253 women in the 16th to 18th weeks of gestation. The result by the present technique in a woman with a confirmed anencephalic fetus was elevated, and in agreement with the results of AFP assays in serum and amniotic fluid. Blood AFP was stable on dried filter paper sent by mail.


Birth weight and risk of angina pectoris: analysis in Swedish twins.
Intrauterine nutrition approximated by birth weight has been shown to be inversely associated with risk of coronary heart disease (CHD). By investigating the association within twin pairs discordant for disease, the influence of genetic and early environmental factors is substantially reduced. We have investigated the association between birth weight and angina pectoris in same-sexed twins with known zygosity included in the population-based Swedish Twin Registry. Self-reports of birth weight and angina pectoris were collected in a telephone interview between 1998 and 2000. The cohort analyses were based on 4594 same-sexed twins, and the within-pair analyses included 55 dizygotic and 37 monozygotic twin pairs discordant for angina pectoris. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by logistic regression. Compared with birth weight between 2.0 and 2.9 kg, low birth weight (<2.0 kg) was associated with increased risk of angina pectoris in the twin cohort, (OR: 1.46; 95% CI: 1.14-1.87), but after adjustment for potential confounders the risk decreased, and did not reach significance. Within twin pairs discordant for angina pectoris, low birth weight was significantly associated with increased risk of angina pectoris within dizygotic twins (adjusted OR: 5.73; 95% CI: 1.59-20.67), but not within monozygotic twins (adjusted OR: 1.20; 95% CI: 0.40-3.58). The results suggest that genetic differences associated with foetal growth and adult risk of CHD may have affected previously reported associations between birth weight and CHD.


Development of on-chip fully automated immunoassay system "μTASWako i30" to measure the changes in glycosylation profiles of alpha-fetoprotein in patients with hepatocellular carcinoma.
Glycosylation profiles significantly change during oncogenesis. Aberrant glycosylation can be used as a cancer biomarker in clinical settings. Different glycoforms can be separately detected using lectin affinity electrophoresis and lectin array-based methods. However, most methodologies and procedures need experienced technique to perform the assays and expertise to interpret the results. To apply glycomarkers for clinical practice, a robust assay system with an easy-to-use workflow is required. Wako's μTASWako i30, a fully automated immunoanalyzer, was developed for in vitro diagnostics based on microfluidic technology. It utilizes the principles of liquid-phase binding assay, where immunoreactions are performed in a liquid phase, and electrokinetic analyte transport assay. Capillary electrophoresis on microfluidic chip has enabled the detection of different glycoform types of alpha-fetoprotein (AFP), a serum biomarker for hepatocellular carcinoma. AFP with altered glycosylation can be separated based on the reactivity to Lens culinaris agglutinin on electrophoresis. The glycoform AFP-L3 was reportedly more specific in hepatocellular carcinoma. This assay system can provide a high sensitivity and rapid results in 9 min. The test results for ratio of AFP-L3 to total AFP using μTASWako i30 are correlated with those of conventional methodology. The μTASWako assay system and the technology can be utilized for glycosylation analysis in the postgenomic era.


Cellulose I nanocrystals (CNCs I) prepared in mildly acidic lithium bromide trihydrate (MALBTH) and their application for stabilizing Pickering emulsions.
This study proposed a sustainable method to prepare cellulose I nanocrystals (CNCs I) from microcrystalline cellulose (MCC) in a mildly acidic lithium bromide trihydrate (MALBTH) system, a concentrated (50 wt%) solution of LiBr in water with recyclable formic acid (FA). First, the MCC was treated in the MALBTH system to generate CNCs with a uniform size, yield higher than 68.49% and crystallinity of 84.02%. Then, the CNCs could application for stabilizing Pickering emulsions for at least 15 days. Furthermore, FA was easily recycled from the MALBTH system, and the yield of the CNCs produced from the hydrolysis of MCC by using the recycled FA was still higher than 60%. Finally, this study provided a sustainable and green production of CNCs. A low-cost and environmentally friendly pathway to recover FA from the MALLBTH system at a high yield was still realized.


Progesterone Receptor Coregulators as Factors Supporting the Function of the Corpus Luteum in Cows.
Progesterone receptor (PGR) for its action required connection of the coregulatory proteins, including coactivators and corepressors. The former group exhibits a histone acetyltransferase (HAT) activity, while the latter cooperates with histone deacetylase (HDAC). Regulations of the coregulators mRNA and protein and HAT and HDAC activity can have an indirect effect on the PGR function and thus progesterone (P4) action on target cells. The highest mRNA expression levels for the coactivators-histone acetyltransferase p300 (P300), cAMP response element-binding protein (CREB), and steroid receptor coactivator-1 (SRC-1)-and nuclear receptor corepressor-2 (NCOR-2) were found in the corpus luteum (CL) on days 6 to 16 of the estrous cycle. The CREB protein level was higher on days 2-10, whereas SRC-1 and NCOR-2 were higher on days 2-5. The activity of HAT and HDAC was higher on days 6-10 of the estrous cycle. All of the coregulators were localized in the nuclei of small and large luteal cells. The mRNA and protein expression levels of the examined coactivators and corepressor changed with the P4 level. Thus, P4 may regulate CL function via the expression of coregulators, which probably affects the activity of the PGR.


Effectiveness of remdesivir for the treatment of hospitalized COVID-19 persons: A network meta-analysis.
Several randomized clinical trials (RCTs) that investigated the effectiveness of remdesivir for the treatment of coronavirus disease-2019 (COVID-19) have generated inconsistent evidence. The present study aimed to synthesize available RCT evidence using network meta-analyses (NMAs). Both blinded and open-label RCTs in PubMed database from inception to 7 June 2020 that contained "remdesivir", "Covid-19", and "trial" in the abstracts conducted on hospitalized COVID-19 persons were identified and screened. The studies must have at least one remdesivir arm and evaluated one of the pre-specified outcomes. The outcomes were clinical improvement between days 10 to 15 after randomization and clinical recovery during the follow-up period. The identified literature was supplemented with relatively recent studies that were known to the researchers if not already included. Frequentist NMAs with random effects were conducted. Both 10-day and 5-day remdesivir regimens were associated with higher odds of clinical improvement (odds ratio [OR] of 10-day regimen: 1.35, 95% confidence interval [CI], 1.09-1.67); OR of 5-day regimen: 1.81, 95% CI, 1.32-2.45, and higher probabilities of clinical recovery (relative risk [RR] of 10-day regimen: 1.24, 95% CI, 1.07-1.43; RR of 5-day regimen: 1.47, 95% CI, 1.16-1.87 compared with placebo. Remdesivir may have clinical benefits among hospitalized COVID-19 persons.


Induction of mast cell secretion by parathormone.
The biologically active fragment of human parathormone (PTH) and intact bovine PTH were found to induce secretion of both serotonin and histamine from rat peritoneal mast cells in vitro. Release of serotonin and histamine was demonstrated with 25 units/ml PTH or higher. This level is within the higher limits of the elevated PTH levels found in advanced uremia. Mast cell secretion by PTH was dose, time and energy dependent and was not cytotoxic. Although mast cell activation was independent of extracellular calcium, it required intracellular calcium, thus resembling the action of certain other peptide secretagogues. Intradermal injection of PTH induced immediate increases in vascular permeability suggesting that PTH could induce mast cell secretion in vivo. Light and electron microscopic observations confirmed mast cell degranulation by exocytosis. These results demonstrate that elevated levels of PTH can induce mast cell secretion in vitro and in vivo and suggest a possible role for mast cells in the pathophysiology of non-allergic disease states.


Improved transfection efficiency of chicken gonadal primordial germ cells for the production of transgenic poultry.
Electroporation is a common method of DNA transfection for many types of eukaryotic cells, but has not been attempted in avian primordial germ cells (PGCs). DNA uptake in chicken primordial germ cells (PGCs) was tested using electroporation with and without dimethyl sulfoxide (DMSO). Gonadal tissue and chicken embryonic fibroblasts (CEFs) were isolated from 6-day-old embryos (stage 29), transfected with pCMV beta carrying the bacterial lacZ gene, and cultured for 24 h. Gonadal primordial germ cells (gPGCs) were purified from culture using a Ficoll gradient. The addition of DMSO significantly increased the transfection efficiency of gPGCs but had no effect on chicken embryonic fibroblasts. Electroporation of gPGCs resulted in an 80% transfection efficiency compared with about 17% observed with liposomes. Approximately 200 transfected gPGCs were injected into 2.5-day-old (stage 17) recipient embryos and the eggs were incubated for an additional 3.5 days, 7.5 days or to hatching. The exogenous gene was detectable in 100%, 67% and 41% of the 6-day-old (stage 29), 10-day-old (stage 36) recipient embryos and hatched chicks gonads, respectively. PCR analysis of DNA from the hatched chicks showed that exogenous lacZ DNA was detected only in the gonad and not the liver and heart. These results indicated that electroporation was a suitable means of transfecting avian gPCGs for the goal of producing transgenic poultry.


Malabsorption associated with diarrhea and intestinal infections.
An episode of diarrhea causes weight loss and a temporary cessation of growth in infants and children. Diarrhea is accompained by malabsorption of sugars, nitrogen, fats, and micronutrients. The mechanisms by which acute diarrheal disease produce malabsorption have not been studied carefully. The nutritional costs of malabsorption may pose a major threat if diarrhea becomes chronic or recurrent. The hydrogen breath test for carbohydrate malabsorption does not require intubation or blood drawing and can be used in children to help clarify the importance of carbohydrate intolerance in the duration and perpetuation of acute diarrhea and intestinal bacterial overgrowth.


BLAS3 optimization for the Godson-3B1500.
This paper proposes a performance model for general matrix multiplication (GEMM) on decoupled access/execute (DAE) architecture platforms, in order to guide improvements of the GEMM performance in the Godson-3B1500. This model focuses on the features of access processors (APs) and execute processors (EPs). To reduce the synchronization overhead between APs and EPs, a synchronization module selection mechanism (SMSM) is presented. Furthermore, two optimized algorithms of GEMM for DAE platforms based on the performance model are proposed for ideal performance. In the proposed algorithms, the kernel functions are optimized with single instruction multiple data (SIMD) vector instructions, and the overhead of AP is almost overlapped with EP by taking full advantage of the features of the architecture. Moreover, the synchronization overhead can be reduced according to the SMSM. In the end, the proposed algorithms are tested on the Godson-3B1500. The experimental results demonstrate that the computing performance of dGEMM reaches 91.9% of the theoretical peak performance and that zGEMM can reach 93% of the theoretical peak performance.


Prevalence and risk factors of Giardia duodenalis in dogs from Romania.
The protozoan Giardia duodenalis is a mammalian-infecting parasite that produces diarrhoea and malabsorption in its hosts. A survey to investigate canine infections with G. duodenalis in Romania was undertaken between June 2008 and December 2009. The objectives of the study were to (i) estimate the prevalence of infection in different dog populations (kennels, shelters, shepherd, household) using microscopy and a commercially available enzyme-linked immunosorbent assay (ELISA) test kit; (ii) to establish the level of agreement and characteristics of the tests; and (iii) to identify risk factors for infection by multivariate logistic regression models. Faecal samples were collected from 614 dogs aged from 1 month to 16 years (mean ± SD=2.88 ± 2.86 years). Each sample was tested for the presence of cysts using a flotation method with saturated sodium chloride solution and 416 out of 614 stool samples were further examined for the presence of G. duodenalis specific antigens using Giardia Microwell ELISA (SafePath™ Laboratories). Giardia cysts were identified in 8.5% of total dogs (52/614) and statistical significantly more frequently in dogs living in communities. The cysts prevalence according with dog populations was as follows: 7.2%(9/125) in kennel dogs; 16.5%(27/164 in shelter dogs; 4.3%(2/46) in shepherd dogs; 4.8%(4/84) in household dogs from urban areas; and 5.1%(10/195) in household dogs from rural areas. The overall prevalence of Giardia infection by ELISA was 34.6% (144/416). The prevalence was significantly higher in kennel dogs (50%; 13/26), shelter dogs (47.7%; 74/155) and shepherd dogs (40.5%; 17/42) than in household dogs from urban areas (34.1%; 15/44) and household dogs from rural areas (16.8%; 25/149). It was noticed poor agreement between microscopy and ELISA (k=0.19). The microscopy performed best, with an Youden Index of 0.74, a Se of 73.68% and a Sp of 100%. ELISA had 100% Sp, but only 19.44% Se. Young dogs (up to 12 months age) and living in communities were identified as risk factors for infection by multivariate logistic regression analysis. 71.2% (37/52) Giardia cysts positive dogs presented co-infections with other intestinal parasites: Toxocara canis (14/52; 26.9%), Isospora ohioensis (12/52; 23.1%), Ancylostoma caninum (9/52; 17.3%), Uncinaria stenocephala (7/52; 13.5%), Trichocephalus vulpis (6/52; 11.5%), Hammondia heydorni/Neospora caninum (5/52; 9.6%), Sarcocystis spp. (5/52; 9.6%), Isospora canis (4/52; 7.7%), Capillaria aerophila (3/52; 5.8%), Strongyloides stercoralis (2/52; 93.8%), Dipylidium caninum (1/52; 1.9%) and Toxascaris leonina (1/52; 1.9%).


Providing Equitable Postpartum Breastfeeding Support at an Urban Academic Hospital.
To equitably increase exclusive breastfeeding at hospital discharge among obstetrician/gynecologist resident service clients by 20% over 8 weeks. This quality improvement project used a plan-do-study-act format to implement interventions with patients and staff based on the Baby-Friendly Hospital Initiative. Run charts were used to evaluate intervention effects over time according to Institute for Healthcare Improvement criteria, and outcome data informed tests of change for subsequent cycles. Postpartum clients of an obstetrician/gynecologist resident service were found to be less likely to exclusively breastfeed compared to the hospital average (7% vs. 34%) at baseline. A baseline resident client survey (n = 20) showed that 75% believed it best to give human milk plus formula. Of 186 postpartum participants, 65% identified as breastfeeding at the time of birth (53% of Hispanic participants [n = 99], 52% of non-Hispanic Black participants [n = 44], and 73% of non-Hispanic White participants [n = 33]). The World Health Organization's revised Implementation Guidance for the Baby-Friendly Hospital Initiative provided the basis for all interventions, which included a prenatal infant feeding plan, postpartum educational video with teach-back, cue-based feeding log, breastfeeding education guidelines for postpartum nurses, and team engagement via huddles. Measures assessed whether each intervention met the intended goals. Rates of exclusive breastfeeding at hospital discharge were 7% at baseline and 13% after implementation. Rates of exclusive breastfeeding among Black clients were 0% at baseline and 16% after implementation. Clients demonstrated Baby-Friendly knowledge (teach-back average, 89%) but continued to supplement with formula, most often related to supply concerns (65%). Intentionally equitable implementation of the Baby-Friendly steps may ameliorate racial disparities in breastfeeding during the early postpartum period. Preparing families to exclusively breastfeed should begin prenatally.


Clinical efficacy of bowel perfusion assessment during laparoscopic colorectal resection using laser speckle contrast imaging: A matched case-control study.
Disadvantages of bowel perfusion assessment with indocyanine green fluorescence angiography include the need for a fluorophore and the subjective nature of the assessment. This study was performed to evaluate the clinical efficacy of bowel perfusion assessment using laser speckle contrast imaging (LSCI) during laparoscopic colorectal surgery. The study population comprised the first 27 consecutive patients who underwent laparoscopic left-sided colorectal resection with intraoperative perfusion assessment using LSCI. The operative outcomes of these patients were compared with those of a matched group of patients without perfusion assessment. We analyzed the flux data expressed in laser speckle perfusion units. After propensity score matching, we found no significant between-group differences in the patients' characteristics with the exception of the cancer stage. No patients undergoing LSCI perfusion assessment developed anastomotic leakage, but five (18.5%) patients in the control group did, at a significantly higher rate in male patients (P = .042). There were no significant differences in other operative outcomes. The laser speckle perfusion unit values after ligating marginal vessels were significantly lower than before ligation (P < .01). With respect to anastomotic leakage, LSCI may improve patient outcomes after colorectal surgery. This technique appears to be a superior tool with the advantages of measurement repeatability and quantitativity and no need for a fluorophore.


Short-term administration of tibolone plus GnRH analog before laparoscopic myomectomy.
To evaluate whether tibolone modifies the effectiveness of gonadotropin-releasing hormone (GnRH) analog administered before laparoscopic myomectomy. Prospective, randomized, open, placebo-controlled clinical trial (Canadian Task Force classification I). University-affiliated hospital. Sixty-six women with symptomatic leiomyomas. Patients received 2 months of treatment with GnRH analog and iron plus tibolone (group A) or placebo (group B); group C received only iron. Laparoscopic myomectomy was performed after medical treatment. Uterine volume, number and volume of leiomyomas, echogenicity and volume of the largest leiomyomas, hematologic values, and myoma-related symptoms were evaluated at baseline, 1 week before, and 1 week after surgery. We observed significant (p <0.05) reductions in uterine and leiomyomata volume, myoma-related symptoms, and improvement in hematologic values before surgery in groups A and B, without significant difference between groups compared with baseline values and group C. Operating time and blood loss were significantly (p <0.05) lower in groups A and B, without significant difference compared with group C. After surgery, significant numbers of women in group C had worsening of hematologic values (p <0.05). Adding tibolone to the GnRH analog regimen before laparoscopic myomectomy does not modify the effectiveness of GnRH analog administered alone.


A longitudinal examination of African American adolescent females detained for status offense.
Behaviors like truancy, running away, curfew violation, and alcohol possession fall under the status offense category and can have serious consequences for adolescents. The Juvenile Justice and Delinquency and Prevention Act prohibited detaining status offenders. We explored the degree to which African American adolescent girls were being detained for status offenses and the connections to their behavioral health risks and re-confinement. 188 African American girls (aged 13-17), recruited from detention facilities, were surveyed at baseline and 3-month follow-ups. Logistic regression models estimated the likelihood of longitudinal re-confinement, controlling for sexual and behavioral health risk factors. One third of the overall sample was detained for a status offense. Status offenders were exposed to higher peer risk profiles. At follow-up, nearly 39% of status offenders reported re-confinement. Compared to youth with other offenses, those who violated a court order (type of status offense) were 3 times more likely to be re-confined. Controlling for sexual and behavioral health risk factors, the odds of re-confinement was not statistically significant. Overall findings suggest that courts and detention facilities must devote specialized resources to addressing the socio-behavioral needs of African American girls with status offenses so as not to use detention as an intervention.


MiR-30a regulates the proliferation, migration, and invasion of human osteosarcoma by targeting Runx2.
Osteosarcoma (OS) is the most common primary malignant bone tumor in young patients. However, treatment paradigms and survival rates have not improved in decades. MicroRNAs have been shown to be critical regulators of physiological homeostasis and pathological process, including bone disease. Nearly half of the microRNA (miRNA) genes are located at genomic regions and fragile sites known to be frequently deleted or amplified in various kinds of cancers. In this study, we investigated the role miR-30a in OS. A negative correlation between miR-30a expression and malignant grade was observed in OS cell lines. The overexpression of miR-30a reduced proliferation, migration, and invasion in 143B cells and the inhibitor of miR-30a increased proliferation, migration, and invasion in Saos2 cells. Further studies revealed that runt-related transcription factors 2 (Runx2) was a regulative target gene of miR-30a. Rescue assay significantly reversed the effects of overexpressing or inhibiting miR-30a. miR-30a also suppressed tumor formation and pulmonary metastasis in vivo. All the results suggest a critical role of miR-30a in suppressing proliferation, migration, and invasion of OS by targeting Runx2.


Ultrasonic imaging of molecular targets.
Today nuclear medicine is the only modality that is clinically successful in molecular imaging. However, other modalities compete with its excellent sensitivity in imaging molecular targets. In the last 10 years ultrasound imaging has shown the potential to provide sufficiently high sensitivity for the molecular imaging of vascular targets. These advances are based on the joint development of microbubble contrast media and the methods to image them with high sensitivity. Ultrasound-contrast-enhanced imaging strategies make use of the specific physical properties of microbubbles such as resonance, nonlinear oscillation, and collapse. The size of microbubbles limits their use to the vascular space. Thus, the main applications of ultrasound for molecular imaging are inflammation, thrombi, and angiogenesis, for which successful contrast enhancement has been achieved in animal models. Main molecular targets used to date include selectins, alpha(v)beta(3) or alpha(5)beta(1) integrins, glycoprotein (GP) IIb/IIIa, intracellular adhesion molecule ICAM-1, and vascular endothelial growth factor receptor VEGFR2. Results from animal studies indicate that ultrasound could play a major role in vascular molecular imaging for diagnosis and treatment monitoring. Additional effects of insonified microbubbles (e.g., opening of the blood-brain barrier or increased transfection efficiency in gene therapy) are attributed to the transient opening of cell membranes known as "sonoporation" and demonstrate further potential for integrated diagnosis and therapy.


Chemogenetic manipulation of microglia inhibits neuroinflammation and neuropathic pain in mice.
Microglia play an important role in the central sensitization and chronic pain. However, a direct connection between microglial function and pain development in vivo remains incompletely understood. To address this issue, we applied chemogenetic approach by using CX3CR1creER/+:R26LSL-hM4Di/+ transgenic mice to enable expression of inhibitory Designer Receptors Exclusively Activated by Designer Drugs (Gi DREADD) in microglia. We found that microglial Gi DREADD activation inhibited spinal nerve transection (SNT)-induced microglial reactivity as well as chronic pain in both male and female mice. Gi DREADD activation downregulated the transcription factor interferon regulatory factor 8 (IRF8) and its downstream target pro-inflammatory cytokine interleukin 1 beta (IL-1β). Using in vivo spinal cord recording, we found that activation of microglial Gi DREADD attenuated synaptic transmission following SNT. Our results demonstrate that microglial Gi DREADD reduces neuroinflammation, synaptic function and neuropathic pain after SNT. Thus, chemogenetic approaches provide a potential opportunity for interrogating microglial function and neuropathic pain treatment.


Occurrence of bufotenin in the Osteocephalus genus (Anura: Hylidae).
Bufotenin (5-hydroxy-N,N-dimetyltryptamine) is a tryptamine alkaloid widely spread among anuran families as a component of their chemical defense system, acting as a potent hallucinogenic factor, showing similar activity to LSD upon interaction with the 5HT2 human receptor. This work demonstrates the presence of bufotenin in the skin secretion of three arboreal amphibian species of the Osteocephalus genus (Osteocephalus taurinus, Osteocephalus oophagus and Osteocephalus langsdorffii) from the Amazon and the Atlantic rain forests using RP-HPLC, ESI-MS/MS, UV, IR and multidimensional NMR techniques. To our knowledge, this is the first description of bufotenin in the Osteocephalus genus, so far.


Optimum design of family structure and allocation of resources in association mapping with lines from multiple crosses.
Family mapping is based on multiple segregating families and is becoming increasingly popular because of its advantages over population mapping. Athough much progress has been made recently, the optimum design and allocation of resources for family mapping remains unclear. Here, we addressed these issues using a simulation study, resample model averaging and cross-validation approaches. Our results show that in family mapping, the predictive power and the accuracy of quatitative trait loci (QTL) detection depend greatly on the population size and phenotyping intensity. With small population sizes or few test environments, QTL results become unreliable and are hampered by a large bias in the estimation of the proportion of genotypic variance explained by the detected QTL. In addition, we observed that even though good results can be achieved with low marker densities, no plateau is reached with our full marker complement. This suggests that higher quality results could be achieved with greater marker densities or sequence data, which will be available in the near future for many species.


The effects of the c-kit blocker glivec on the contractile response of urinary bladder.
To investigate the effects of imatinib (Glivec) on the urinary bladder contraction and excitation induced by neurostimulation, therefore to clarify the relationships between the bladder interstitial cell of Cajal (ICC) and the neural signals. In in vivo experiments, pelvic nerves of rats were stimulated by square-wave pulses. The contractile response was recorded before and 40 min after the administration of medications (atropine, Glivec, and ketotifen). In in vitro experiments, the bladder contractile response induced by acetylcholine with or without Glivec was evaluated. The space relationship between ICC and neural fibers were observed with double-labeled fluorescence using primary antibodies (anti-c-kit and anti-vesicular acetylcholine transferase) and secondary fluorescent antibodies (Alexa 488 and Alexa 594; Molecular Probes, Eugene, OR). Atropine and Glivec could significantly inhibit the bladder contractile response induced by the electrical stimulation in a dose-dependent manner, while ketotifen did not obviously affect bladder contractile response. In in vitro experiments, Glivec did not affect acetylcholine-induced bladder contractile response. The location of ICC in close proximity to cholinergic nerve fibers was confirmed by double-labeled fluorescence. Bladder ICC play an important role as intermediaries in the transmission of cholinergic signals from nerve to smooth muscle cells.


Effect of Huogu II Formula (II) with medicinal guide Radix Achyranthis Bidentatae on bone marrow stem cells directional homing to necrosis area after osteonecrosis of the femoral head in rabbit.
To investigate the effect of Huogu II Formula (II) with medicinal guide Radix Achyranthis Bidentatae (Ach) on bone marrow stem cells (BMSCs) homing to necrosis area after osteonecrosis of the femoral head (ONFH) frozen by liquid nitrogen in rabbit as well as to explore the mechanism of prevention and treatment for ONFH. The animal model of ONFH was established by liquid nitrogen frozen on the rabbit left hind leg. Forty-eight Japanese White rabbits were randomly assigned to sham-operated group, model group, Huogu II group, and Huogu II plus Ach group, with 12 rabbits in each. During the course of ONFH animal model establishment, all rabbits were subcutaneously injected with recombinant human granulocyte colony-stimulating factor [rhG-CSF, 30 μg/(kg·day) for continuous 7 days]. Meanwhile, normal saline and decoction of the two formulae were administrated by gavage, respectively. White blood cells (WBC) were counted in peripheral blood before and after injection of rhG-CSF. Materials were drawn on the 2nd and 4th weeks after model built; bone glutamine protein (BGP) and bone morphogenetic protein 2 (BMP2) levels in serum were tested. Histopathologic changes were observed by hematoxylin and eosin (HE) staining. BMP2 mRNA levels were detected with in situ hybridization (ISH) staining. 5-Bromo-2'-deoxyuridine (BrdU) and stromal cell derived factor 1 (SDF-1) were measured by immunohistochemical assay in femoral head of the left hind leg. Compared with the shamoperated group, the ratio of empty lacuna, serum BGP, and SDF-1 level in the model group increased significantly, and BMP2 in both serum and femoral head decreased significantly. However, in comparison with the model group, the empty lacuna ratio of Huogu II group and Huogu II plus Ach group decreased obviously in addition to the levels of serum BGP and BMP2, and the expressions of BMP2 mRNA, BrdU, and SDF-1 increased significantly. Above changes were particularly obvious in Huogu II plus Ach group. BGP and SDF-1 on the 2nd week and empty lacuna rate and serum BMP2 level on the 4th week in Huogu II group significantly exceeded their counterparts. On the 2nd week, only in Huogu II plus Ach group that the BrdU counting rose significantly. On the 4th week, empty lacuna rate and serum BMP2 level in Huogu II plus Ach group exceeded those in Huogu II group distinctively. To a certain extent, the medicinal guide Ach improves the preventive and therapeutic effects of Huogu II Formula on experimental ONFH model. The possible mechanism of this is related to its promoting effect on directional homing of BMSCs to the necrosis area.


A comparison of techniques for isolation of the outer membrane proteins of Haemophilus influenzae type b.
We compared several rapid techniques used for extraction of outer membrane proteins from gram-negative enteric bacteria to Haemophilus influenzae type b. After lysis of cells with a French press, the inner and outer membranes were separated by isopycnic centrifugation. Each membrane was identified by density, morphology, enzymatic activity, and susceptibility to solid-phase iodination of intact cells. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis, we identified 10 polypeptides which were enriched in the outer membrane band compared to the inner membrane band. Using these proteins, we compared the polypeptide pattern of outer membranes with that obtained by (1) selective solubilization with sodium dodecyl-beta-D-maltoside, octyl-beta-D-glucopyranoside, Triton X-100, sodium, or cholamidopropyl dimethylaminopropanesulfonate; (2) extraction with chaotropic agents and heat; and (3) differential centrifugation of vesicles shed during transition from log growth phase to stationary growth phase. There were definable differences between the polypeptide pattern of membranes obtained with each rapid technique compared to the polypeptide pattern of isolated outer membranes. The polypeptide pattern of lithium extracts and the Triton X-100 insoluble fractions of total membranes most closely approximated the polypeptide pattern of isopycnically isolated outer membranes. Depending on the outer membrane protein sought, one of these rapid techniques can be utilized when a rapid method of outer membrane protein isolation is required.


Measuring physiological and pathological femoral anteversion using a biplanar low-dose X-ray system: validity, reliability, and discriminative ability in cerebral palsy.
The aims of this study were to evaluate the concurrent validity and reliability of a low-dose biplanar X-ray system (Ld-BPR) for the measurement of femoral anteversion (FA) by comparing Ld-BPR-based three-dimensional measures with CT-scan-based measures and to assess the discriminative ability of this method in children with cerebral palsy. Fifty dry femora were scanned using both a CT scan and the Ld-BPR system. Ten femora were artificially modified to mimic a range of anteversion from -30° to +60° and scanned by both modalities. FA was quantified using the images from both modalities and statistically compared for concurrent validity. Intra- and inter-observer reliability of the Ld-BPR system was also determined. Further, Ld-BPR data from 16 hemiplegic and 22 diplegic children were analyzed for its discriminative ability. The concurrent validity between the Ld-BPR and CT-scan measures was excellent (R (2) = 0.83-0.84) and no significant differences were found. The intra- and inter-trial reliability were excellent (ICCs = 0.98 and 0.97) with limits of agreement of (-2.28°; +2.65°) and (-2.76°; +3.38°) respectively. Further, no significant effects of angle or method were found in the sample of modified femora. Ld-BPR measures for FA were significantly different between healthy and impaired femora. The excellent concurrent validity with the CT scan modality, the excellent reliability, and the ability to discriminate pathological conditions evaluated by this study make this radiological method suitable for a validated use across hospitals and research institutes.


Association between functional variants in BIRC5/survivin gene 3' untranslated region and mRNA expression in lymphoblastoid cell lines.
Baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5)/survivin genetic microRNA (miRNA) binding site variants in the 3' untranslated region (3'UTR) are known to be significantly associated with cancer risk. However, the roles of genetic variants in BIRC5/survivin gene 3'UTRs and post-transcriptional regulation have not been elucidated. In the present study, we revealed that rs1042489, rs1042542, rs17882360, rs2239680, rs2661694 and rs4789560 in the BIRC5/survivin 3'UTR have potential miRNA binding sites using bioinformatics analysis. However, only rs1042489 was significantly associated with BIRC5/survivin mRNA expression in lymphoblastoid cell lines (P=0.030); rs1042489 may be a putative variant mediating the post-transcriptional regulation of the target BIRC5/survivin gene. An in-depth understanding of how 3'UTR variants regulate BIRC5/survivin activity is expected to pave the way to targeting the BIRC5/survivin pathway in cancer therapy.


The formation of hydrogen peroxide during the oxidation of reduced nicotinamide adenine dinucleotide by cytochrome o from Vitreoscilla.
The formation of hydrogen peroxide during the oxidation of NADH by purified preparations of cytochrome o has been demonstrated by employing three independent methods: polarographic, colorimetric, and fluorometric. The first two methods were used to assay for the accumulation of hydrogen peroxide and showed that hydrogen peroxide did accumulate as a product, but only about 30% of the oxygen consumed or 15 to 20% of the NADH oxidized was recoverable as hydrogen peroxide. This lack of 1:1 stoichiometry was not due to residual catalase activity in these preparations which could be eliminated by freeze-thawing. Thus, hydrogen peroxide may not be the sole or primary product of the NADH-cytochrome o oxidase reaction. The fluorometric assay could be coupled directly to the NADH-cytochrome o oxidase reaction in one medium, and this method showed that hydrogen peroxide was generated continuously from the beginning of the reaction in a 1:1 stoichiometry, hydrogen peroxide generated to NADH oxidized. This result suggests that hydrogen peroxide is an intermediate that can be trapped efficiently under the conditions of the fluorometric assay, whereas under the conditions of the first two assays most of the hydrogen peroxide generated undergoes further reaction. Exogenously added FAD or FMN increased the percentage of hydrogen peroxide that accumulated in the NADHcytochrome o oxidase reaction. Flavin is believed to act on the reductase side of cytochrome o so the increased percentage of hydrogen peroxide is not likely to result from the direct reaction of reduced flavin with oxygen.


The physician and the arthritis patient: informed partners in therapy.
By creating an environment for treatment and rehabilitation which is simultaneously functional, attractive, and clearly responsive to the arthritis patient's medical, functional and emotional needs, the physician sends the message that he is concerned about all aspects of care and willing to do his share in promoting and maintaining the therapeutic partnership with the patient.


Biokinetical analysis of the movements of the pelvic limb of the horse and the role of the muscles in the walk and the trot.
The movements of the right hind limb of horses with normal locomotion were studied using cinephotography and electromyography. A model of the cycle of a stride in the walk and the trot was constructed and the kinetic parameters of the segments of the limb were calculated. A good correlation was obtained between the kinetics and the periods of the cycle of a stride during which individual muscles display activity. The results of this study demonstrate that: at placing and lifting, i.e., when a change occurs in the direction of the movement of the limb; b) At the walk, the greatest forces operant at the centres of gravity of the limb segments in the direction of the progression are present in the beginning and the end of the support phase. The first top in the acceleration curve is produced by activity in the retractors of the limb (hamstrings, gluteus medius muscles). At the end of the support phase, when activity in the retractors of the limb no longer exists, the dynamic effect of the moment of the weight about the point of support of the stabilized inclined limb, as well as the elastic resilience of the muscular tissue are responsible for the push-off. At the trot, the greatest forces in the direction of progression are exerted in the middle of the support phase and are largely due to muscular action; c) In the second part of the support phase in the walk, the stifle flexes and the hock extends, which results in stretching the tendinous peroneus tertius and subsequently in flexion of the hock as soon as the hoof starts rolling over; d) The gastrocnemius and cranial tibial muscles in the reciprocal tendinous apparatus centre the line of action of the resultant load on the tibia during the locomotion and reduce the strain due to bending; e) At the end of the support phase, the action of the rectus femoris muscle is replaced by that of the vastus lateralis, which prevents hooking of the patella on the medial ridge of the femoral trochlea by rotating it laterally around a longitudinal axis.


Low Rates of Colonoscopy Follow-up After a Positive Fecal Immunochemical Test in a Medicaid Health Plan Delivered Mailed Colorectal Cancer Screening Program.
Follow-up colonoscopy after a positive fecal immunochemical test (FIT) is necessary for colorectal cancer (CRC) screening to be effective. We report colonoscopy follow-up rates after a positive FIT overall and by population characteristics in the BeneFIT demonstration pilot, a Medicaid health insurance plan-delivered mailed FIT outreach program. In 2016, 2 health insurance plans in Oregon and in Washington state mailed FIT kits to Medicaid patients who, based on claims data, were overdue for CRC screening. We report follow-up colonoscopy completion rates after positive FIT, and differences in completion rates by age, sex, race, ethnicity, preferred language, and number of primary care visits in the prior year. This research was human subjects approved with a waiver of consent for data collection. The FIT positivity rates in Health Plan Oregon and Health Plan Washington were 7.9% (39/488) and 14.6% (125/857), respectively. Colonoscopy completion rates within 12 months of the positive test were 35.9% (14/41) in Health Plan Oregon and 32.8% (41/125) in Health Plan Washington. Colonoscopy completion rates were higher among individuals who preferred a language other than English (Non-English speakers 70.0%, English speakers 31.3%, P = .04). In a health plan-delivered mailed FIT outreach program, follow-up colonoscopy rates after a positive test were low. Additional interventions are needed to assure colonoscopy after a positive FIT test and to reap the benefits of screening.


Successive surgical repair of a progressive aortic dissection in a case of Loeys-Dietz Syndrome.
The Frozen Elephant Trunk technique is a well-established treatment for aortic dissections (Stanford Type A) involving the aortic arch and descending aorta. The Thoraflex™ Hybrid prosthesis (Vascutek Ltd.), consisting of a proximal flexible conduit and a distal self-expanding covered stent, has consistently shown positive results in the treatment of this condition. The following is a description of such a staged reconstruction using the Thoraflex™ Hybrid Ante-Flo™ device, performed in a patient previously diagnosed with Loeys-Dietz Syndrome. After clamping the aorta proximally, an incision was taken at the distal end of the stent. Here, the distal end of the new prosthesis was inserted into the true lumen of the descending aorta and the stent was deployed. Following this, a bypass was established via the left atrium, and blood was returned to the lower body using the perfusion arm of the prosthesis with the proximal part of the descending aorta clamped. The collar of the prosthesis was sutured proximally to the aorta near the inlying previous stent. Air was removed via the perfusion arm of the prosthesis, which was then oversewn. To date, hybrid prostheses have only been used on the proximal aorta in patients with aortic aneurysms and aortic dissections (Stanford Type A). Using the described technique, it is possible to reconstruct the aortic anatomy using the available prostheses with accuracy and minimal complications.


Pupil capture: prevention and management.
Pupil capture occurs in a small percentage of patients following posterior chamber lens implantation. We noted a 3% incidence in 100 patients using sulcus fixated planar J-loop lenses, a 1% incidence using sulcus fixated angulated J-loop lenses, and a 1% incidence in capsular bag fixated flexible Y-loop lenses. No patients lost vision from pupil capture, and no clinically significant late complications were observed. Pupil capture may be successfully treated in the early postoperative period in some patients by mydriasis and a noninvasive loop compression technique using Q-tips.


Fast-response and highly selective fluorescent probes for biological signaling molecule NO based on N-nitrosation of electron-rich aromatic secondary amines.
Nitric oxide (NO) is a ubiquitous biological messenger molecule, and plays the active roles in the regulation of various physiological processes. Although numerous NO fluorescent probes have also been successfully developed in the past ten years, it still remains challenging to increase the response rate for NO while having the high selectivity and sensitivity. In this work, a simple N-nitrosation reaction of the electron-rich aromatic secondary amine with NO under aerobic condition has been utilized for the first time to construct fluorescent probe for NO. The resulting probe 1, containing a N-benzyl-4-hydroxyaniline moiety as reaction group and a BODIPY dye as fluorescence reporter, could detect NO with the fast fluorescence off-on response (within seconds), high sensitivity (nM level), and excellent selectivity over various reactive oxygen species (ROS) as well as dehydroascorbic acid (DHA), ascorbic acid (AA), and methylglyoxal (MGO). Even in the presence of glutathione (GSH, a high reactive biothiol for NO), the probe still works well for NO. Further, a mitochondria-targetable probe 2 was exploited by introducing a targeted triphenylphosphonium cation into probe 1 scaffold. It's excellent NO sensing performance as well as its ability to specifically target mitochondria and image NO there have been nicely demonstrated. With the two probes, the basal and stimulation-induced NO in RAW264.7 murine macrophages as well as the endogenous NO in endothelial cells after oxygen-glucose deprivation (OGD) have been successfully visualized.


The effect of Siltex texturing and povidone-iodine irrigation on capsular contracture around saline inflatable breast implants.
A prospective, controlled, and blinded clinical study was performed on 56 patient volunteers to determine the effects of two independent variables--the Siltex textured inflatable implant and povidone-iodine irrigation--on the incidence of fibrous capsular contracture following retromammary augmentation. Each patient was randomly assigned both textured and smooth implants and povidone-iodine and saline irrigation, so that each patient served as her own control. The Siltex devices experienced an incidence of class III-IV contracture of only 2 percent, as compared with an incidence of 40 percent around the smooth devices. Most patients, however, preferred the smooth devices despite the higher contracture incidence because the Siltex device was more easily palpable. Povidone-iodine did not reduce the final incidence of contracture. It appeared to delay the onset of contracture, but not with statistical significance.


Cerebral ventricular infusion of excess calcium in the rat: effects on sleep states, behavior and cortical EEG.
Sleep and behavior of the rat were recorded during cerebroventricular infusion of artificial cerebrospinal fluid (aCSF) containing regular or excess concentrations of calcium. Three different types of aCSF were used for control infusions. Depending on the ionic composition, paradoxical sleep (PS) was reduced by 6--52% during a 1-h aCSF infusion period, whereas the total amount of sleep was not altered. The depression of PS by aCSF could be prevented by increasing the concentration of Ca in the infusate by a factor of 2--5 (2.6--9.1 mM). Infusions of high concentrations of Ca (9.1--54.6 mM) caused feeding and wet-dog shakes. A slow-wave cortical EEG pattern prevailed during feeding elicited by either infusion of excess Ca or systemic administration of a small dose of pentobarbital. It is concluded (a) that the ionic composition of the CSF may selectively influence the occurrence of a sleep state, and (b) that Ca-induced feeding may be related to a covert sedative action of this cation.


Confirmation and an unusual quality of the differentiated keratin peptide (K1) in cultured human squamous cell carcinomas.
Recently K1 keratin peptide (K1, 68 kDa) was found to be present in two kinds of cultured human squamous cell carcinomas (HSCs) using a low-salt aqueous solution, rather than the high-salt solution containing Triton X-100 employed by many researchers up until now. To confirm whether this phenomenon is universal in cultured HSCs we analyzed K1 peptide in four other kinds of HSCs using the same procedures. Moreover, the K1 peptide detected was a little unusual with respect to solubility versus urea concentration. Epidermal K1 peptide is usually solubilized by 6-8 M urea and reductant; however, the K1 peptide in cultured HSCs was about 80-90% extracted by 1-2 M urea in a stepwise extraction procedure. This finding may have important implications regarding evaluation of keratin extracted from normal epidermal and cultured keratinocytes.


Harmful impact of treatment refusal in T3-4M0 endolaryngeal squamous cell carcinoma candidates for total laryngectomy: A STROBE analysis.
To evaluate the consequences of treatment refusal in total laryngectomy (TL) candidates with T3-4M0 endolaryngeal squamous cell carcinoma (SCC). A retrospective observational study was conducted in an inception cohort of 576 isolated T3-4M0 endolaryngeal SCC candidates for TL consecutively managed between 1970 and 2019 in a French university teaching hospital. The main endpoint was survival time and cause of death in 2 groups. Group A, 4.5% of the cohort, consisted of 26 patients who declined any laryngeal treatment. Group B consisted of 550 patients who accepted TL. Accessory endpoints were causes of TL refusal and associated variables. The STROBE guideline was applied. The significance threshold was set at P<0.005. One-and 3-year actuarial survival estimates increased significantly (P<0.0001) from 39% and 15% in group A, to 83% and 63% in group B, respectively. In group A, 92% of causes of death implicated index SCC progression, whereas in group B intercurrent disease, metachronous second primary, locoregional and/or metastatic SCC progression and postoperative complications accounted for 37%, 31%, 29%, and 2%, respectively. The actuarial survival estimates within group A increased significantly (P=0.0003) from 0% at 1-year in patients managed with isolated supportive care to 56% in patients managed with chemotherapy (reaching 0% at 5years). Reasons for TL refusal were fear of surgery, refusal of tracheostoma, loss of physiologic phonation, and certain comorbidities. Age and chronologic period correlated significantly with TL refusal. Median age decreased (P<0.001) from 69years in group A to 58 years in group B. Percentage TL refusal increased (P<0.0001) from 2% to 11% before and after start 1990, respectively. The current study determined loss of survival with refusal of any laryngeal treatment including TL, noted benefit of chemotherapy associated to supportive care, and discussed the possible contribution of immunotherapy.


Exact mass analysis of sulfur clusters upon encapsulation by a polyaromatic capsular matrix.
Structural determination of inorganic clusters relies heavily on mass spectrometry because of, in most cases, their poor responsivities toward nuclear magnetic resonance, ultraviolet/visible, and infrared analyses. Nevertheless, mass spectrometry analysis of oligosulfurs (S n ), which are unique clusters with copious allotropic forms, usually displays their fragment peaks. Here we report that a polyaromatic capsule acts as a supramolecular matrix for the mass determination of the neutral sulfur clusters. Upon encapsulation, molecular ion peaks derived from the host-guest complexes including cyclic S6 and S8 clusters are exclusively detected by common electrospray ionization time-of-flight mass spectrometry analysis. Furthermore, mass spectrometry analysis of a cyclic S12 cluster, which is in situ prepared from two S6 clusters within the matrix upon light irradiation, is achieved by the same way. The present matrix can remarkably stabilize the otherwise labile S6 and S12 clusters in the polyaromatic shell not only under mass spectrometry conditions but also in an ambient solution state.The structures of inorganic clusters are commonly characterized by mass spectrometry (MS), but neutral sulfur clusters heavily fragment under MS conditions, preventing their exact mass determination. Here, the authors successfully perform MS on labile cyclic sulfur clusters by stabilizing them within ionic supramolecular capsules.


The allocation of anatomical traits determines the trade-off between fine root resource acquisition-transport function.
Cortex radius (CR) and stele radius (SR) are important functional traits associated with the nutrient acquisition and transport functions of fine roots, respectively. However, for developmental and anatomical reasons, the resource acquisition-transport relationship of fine roots is expected to be different for different root orders. To address this issue, critical fine root anatomical traits were examined for the first three orders of roots of 59 subtropical woody plants. Designating the most distal fine roots as order one, SR scaled isometrically with respect to root radius (RR) (i.e., SR ∝ RR1.0) in the three root orders, whereas CR scaled allometrically with respect to RR (i.e., CR ∝ RR>1.0) with the numerical values of scaling exponents increasing significantly with increasing root orders thereby indicating a disproportional increase in CR with increasing root orders. There were also differences between normalized root tissue (CR/RR and SR/RR) and RR in different root orders. A negative isometric relationship (i.e., SR/RR ∝ RR-1.0) existed between SR/RR and RR in three order roots, whereas the allometric exponent between CR/RR and RR increased with root order (from 0.88 to 1.55). Collectively, the data indicate that root anatomical and functional traits change as a function of RR and that these changes need to be considered when modeling fine root resource acquisition-transport functions.


Mefloquine damage vestibular hair cells in organotypic cultures.
Mefloquine is an effective and widely used anti-malarial drug; however, some clinical reports suggest that it can cause dizziness, balance, and vestibular disturbances. To determine if mefloquine might be toxic to the vestibular system, we applied mefloquine to organotypic cultures of the macula of the utricle from postnatal day 3 rats. The macula of the utricle was micro-dissected out as a flat surface preparation and cultured with 10, 50, 100, or 200 μM mefloquine for 24 h. Specimens were stained with TRITC-conjugated phalloidin to label the actin in hair cell stereocilia and TO-PRO-3 to visualize cell nuclei. Some utricles were also labeled with fluorogenic caspase-3, -8, or -9 indicators to evaluate the mechanism of programmed cell death. Mefloquine treatment caused a dose-dependent loss of utricular hair cells. Treatment with 10 μM caused a slight reduction, 50 μM caused a significant reduction, and 200 μM destroyed nearly all the hair cells. Hair cell nuclei in mefloquine-treated utricles were condensed and fragmented, morphological features of apoptosis. Mefloquine-treated utricles were positive for the extrinsic initiator caspase-8 and intrinsic initiator caspase-9 and downstream executioner caspase-3. These results indicate that mefloquine can induce significant hair cell degeneration in the postnatal rat utricle and that mefloquine-induced hair cell death is initiated by both caspase-8 and caspase-9.