Mechanism of immonoglobulin G adsorption on mica-AFM and electrokinetic studies.
Adsorption of immunoglobulin G (IgG) from aqueous NaCl solutions of the concentration 10(-3)-0.15M on mica was studied. Initially, the kinetics was evaluated at pH 3.5 by direct AFM imaging. A monotonic increase in the maximum coverage of IgG with NaCl concentration was observed. These results were interpreted in terms of the theoretical model postulating an irreversible adsorption of the protein governed by the random sequential adsorption (RSA) model. Additionally, IgG adsorption and desorption was studied under in situ conditions, with streaming potential measurements. These measurements revealed that the maximum coverage of irreversibly adsorbed IgG varies from 0.37mgm(-2) for 10(-3)M, NaCl to 1.2mgm(-2) for 0.15M, NaCl. The significant role of ionic strength was attributed to the lateral electrostatic repulsion among adsorbed IgG molecules, positively charged at this pH value. These experimental results confirmed that monolayers of irreversibly bound IgG can be produced by adjusting ionic strength of the protein solution. In further experiments the stability and acid base properties of such monolayers were studied using the streaming potential method. It revealed that the monolayers were stable against pH cycling for the range from 3.5 to 9.5. The isoelectric point of mica supported IgG monolayers was 5.9, similar to derived from the micro-electrophoretic measurements in the bulk (5.8). Beside significance for basic sciences, the results indicate that thorough characteristics of IgG can be acquired via streaming potential measurements using microgram quantities of the protein.


Shiga toxin induces decreased expression of the anti-apoptotic protein Mcl-1 concomitant with the onset of endothelial apoptosis.
Shiga toxin (Stx) has been implicated in the pathogenesis of several human and animal disease states. A key host target of Stx is the endothelial cell. Stx induces endothelial cell apoptosis through a mechanism that remains unknown. In the present report, we demonstrate that Stx-1 and Stx-2 inhibit endothelial cell expression of the anti-apoptotic Bcl-2 family member, Mcl-1. Decreased expression of Mcl-1 preceded the onset of Stx-induced apoptosis. Further, Stx-1-induced decrements in Mcl-1 expression correlated in a dose-dependent manner with sensitization to Stx-1-induced apoptosis. Finally, inhibition of Mcl-1 degradation with the proteasome inhibitor, lactacystin, protected against Stx-1-induced apoptosis. These combined data suggest a role for Mcl-1 in protecting endothelial cells against Stx-1-induced apoptosis.


Folic acid-functionalized human serum albumin nanocapsules for targeted drug delivery to chronically activated macrophages.
Activated synovial macrophages play a key role in Rheumatoid Arthritis (RA). Recent studies have shown that folate receptor beta (FRβ) is specifically expressed by activated macrophages. Therefore a folate-based nanodevice would provide the possibility of delivering therapeutic agents to activated macrophages without affecting normal cells and tissues. This study shows for the first time the sonochemical preparation of HSA nanocapsules avoiding toxic cross linking chemicals and emulsifiers used in other methods. Production of HSA nanocapsules was optimized leading to a diameter of 443.5 ± 9.0 nm and a narrow size distribution indicated by a polydispersity index (PDI) of 0.066 ± 0.080. Nanocapsules were surface modified with folic acid (FA) and the FA content was determined to be 0.38 and 6.42 molecules FA per molecule HSA, depending on the surplus of FA employed. Dynamic light scattering was used to determine size, PDI and zetapotential of the produced nanocapsules before and after surface modification. FA distribution on the surface of HSA nanocapsules was localized three-dimensionally after fluorescence labeling using confocal laser scanning microscopy (CLSM). Furthermore, specific binding and internalization of HSA nanocapsules by FRβ-positive and FRβ-negative macrophages, obtained from human peripheral blood mononuclear cells, was demonstrated by flow cytometry. FRβ-expressing macrophages showed an increased binding for FA-modified capsules compared with those without FA.


Subtyping Social Determinants of Health in All of Us: Network Analysis and Visualization Approach.
Social determinants of health (SDoH), such as financial resources and housing stability, account for between 30-55% of people's health outcomes. While many studies have identified strong associations among specific SDoH and health outcomes, most people experience multiple SDoH that impact their daily lives. Analysis of this complexity requires the integration of personal, clinical, social, and environmental information from a large cohort of individuals that have been traditionally underrepresented in research, which is only recently being made available through the All of Us research program. However, little is known about the range and response of SDoH in All of Us, and how they co-occur to form subtypes, which are critical for designing targeted interventions. To address two research questions: (1) What is the range and response to survey questions related to SDoH in the All of Us dataset? (2) How do SDoH co-occur to form subtypes, and what are their risk for adverse health outcomes? For Question-1, an expert panel analyzed the range of SDoH questions across the surveys with respect to the 5 domains in Healthy People 2030 (HP-30), and analyzed their responses across the full All of Us data (n=372,397, V6). For Question-2, we used the following steps: (1) due to the missingness across the surveys, selected all participants with valid and complete SDoH data, and used inverse probability weighting to adjust their imbalance in demographics compared to the full data; (2) an expert panel grouped the SDoH questions into SDoH factors for enabling a more consistent granularity; (3) used bipartite modularity maximization to identify SDoH biclusters, their significance, and their replicability; (4) measured the association of each bicluster to three outcomes (depression, delayed medical care, emergency room visits in the last year) using multiple data types (surveys, electronic health records, and zip codes mapped to Medicaid expansion states); and (5) the expert panel inferred the subtype labels, potential mechanisms that precipitate adverse health outcomes, and interventions to prevent them. For Question-1, we identified 110 SDoH questions across 4 surveys, which covered all 5 domains in HP-30. However, the results also revealed a large degree of missingness in survey responses (1.76%-84.56%), with later surveys having significantly fewer responses compared to earlier ones, and significant differences in race, ethnicity, and age of participants of those that completed the surveys with SDoH questions, compared to those in the full All of Us dataset. Furthermore, as the SDoH questions varied in granularity, they were categorized by an expert panel into 18 SDoH factors. For Question-2, the subtype analysis (n=12,913, d=18) identified 4 biclusters with significant biclusteredness (Q=0.13, random-Q=0.11, z=7.5, P<0.001), and significant replication (Real-RI=0.88, Random-RI=0.62, P<.001). Furthermore, there were statistically significant associations between specific subtypes and the outcomes, and with Medicaid expansion, each with meaningful interpretations and potential targeted interventions. For example, the subtype Socioeconomic Barriers included the SDoH factors not employed, food insecurity, housing insecurity, low income, low literacy, and low educational attainment, and had a significantly higher odds ratio (OR=4.2, CI=3.5-5.1, P-corr<.001) for depression, when compared to the subtype Sociocultural Barriers. Individuals that match this subtype profile could be screened early for depression and referred to social services for addressing combinations of SDoH such as housing insecurity and low income. Finally, the identified subtypes spanned one or more HP-30 domains revealing the difference between the current knowledge-based SDoH domains, and the data-driven subtypes. The results revealed that the SDoH subtypes not only had statistically significant clustering and replicability, but also had significant associations with critical adverse health outcomes, which had translational implications for designing targeted SDoH interventions, decision-support systems to alert clinicians of potential risks, and for public policies. Furthermore, these SDoH subtypes spanned multiple SDoH domains defined by HP-30 revealing the complexity of SDoH in the real-world, and aligning with influential SDoH conceptual models such as by Dahlgren-Whitehead. However, the high-degree of missingness warrants repeating the analysis as the data becomes more complete. Consequently we designed our machine learning code to be generalizable and scalable, and made it available on the All of Us workbench, which can be used to periodically rerun the analysis as the dataset grows for analyzing subtypes related to SDoH, and beyond.


A retrospective study of 20 patients with Kimura's disease from China.
Kimura's disease (KD) is an eosinophilic proliferative lymphoid disease with rare incidence rate and nonspecific clinical symptoms. To investigate the clinical characteristics, diagnosis, treatment, and prognosis of KD. The clinical manifestations, laboratory examination, imaging examination, proposed treatment, and prognosis of 20 patients with KD treated in our hospital were retrospectively analyzed. All cases showed painless masses. The proportion of peripheral blood eosinophils rose in 18 cases (90%), the eosinophil count increased in 14 cases (70%) and the serum immunoglobulin E (IgE) levels were significantly increased in 5 patients (100%). Pathological examination revealed follicular hyperplasia, eosinophils infiltration, and tiny vessels proliferation in KD samples. KD should be considered when the patients suffered head and neck subcutaneous painless mass, increased peripheral blood eosinophils and raised serum IgE level. Pathological examination is the golden standard for diagnosing KD. Surgical intervention, medical treatments, and radiotherapy may be effective for KD treatment. This study might shed a light on improving the diagnosis and treatment for KD.


Hysterical traits and variability of mood in normal men.
In a study of 40 normal men it was found that self-ratings on variability of mood were positively correlated with self-ratings on hysterical traits. These results are similar to those found in normal women and lend support both to the validity of the concept of hysterical personality and to the idea that men and women experience fluctuations of mood in a similar way.


Proximate composition, functional properties, amino acid, mineral and vitamin contents of a novel food: Alhydwan (Boerhavia elegana Choisy) seed flour.
Alhydwan (Boerhavia elegana Choisy) seed flour was evaluated for chemical and nutritional composition, and functional properties in a pursuit to identify an innovative plant with high nutraceuticals value which could be exploited in other food applications. The flour was found to be rich in dietary fiber (30.13%), protein (14.60%), crude fat (11.49%), carbohydrates (30.77%), and ash (6.88%) and encompassed adequate amounts of essential amino acids and minerals, whereas, sucrose constituted 71.3% of total sugar contents. Vitamins analysis revealed that flour is rich in water-soluble vitamins such as Thiamin (B1), Riboflavin (B2) and Niacin (B3), to the amounts of 19.3, 8.2 and 2.3mg/100g, respectively. Results on functional properties demonstrated high water and oil absorption capacities of 6.31 and 2.43g/g, respectively. Foaming capacity, foam stability and emulsion capacity were 9.35%, 6.90%, and 29.60%, respectively. It can be concluded that alhydwan is an excellent food material with a high nutritional value.


Studies on the biosynthesis of cyclitols, XXXVII. On mechanism and function of Schiff's base formation as an intermediary reaction step of myo-inositol-1-phosphate synthase from rat testicles.
It could be shown that the formation of a Schiff's base by myo-inositol-1-phosphate synthase of rat testicles occurs by binding the aldehyde group of the open form of its substrate, D-glucose 6-phosphate, to a lysyl residue of one or both smaller subunits of the enzyme. The participation of the Schiff's base formation in the catalytic process is supported by the observations that (a) no Schiff's base is formed if NAD is removed from the enzyme, and (b) in the presence of NAD, the dehydrogenation step involved in the catalytic mechanism apparently takes place rapidly after the formation of the Schiff's base.


Platelet adhesion and aggregation in pulsatile shear flow: effects of red blood cells.
An in vitro test system was developed to examine the effects of red blood cells (RBC) on shear-induced platelet adhesion (SIPAD) and platelet aggregation (SIPAG). Suspensions of human platelets labeled with Mepacrine and suspended in citrated plasma were exposed to single, continuous or repetitive (120-300x) one second shear stress pulses of varying amplitude (15-100 dyn/cm2) in a cone-plate viscometer in the presence or absence of fresh, untreated (intact) RBC or glutaraldehyde (GLA)-fixed, rigid, adenosine diphosphate (ADP)-depleted (GLA)-RBC. SIPAG was expressed as percent loss of single platelets. SIPAD was assessed by measuring the amount of Mepacrine-related fluorescent material remaining on glass disks in the plate of the viscometer after washing with EDTA-saline to remove platelet aggregates. Intact RBC were twice as effective as GLA-RBC in potentiating SIPAG at all shear stress levels. Potentiation of SIPAD by intact RBC was markedly less than that observed with GLA-RBC at stresses below 50 dyn/cm2. These findings are consistent with the concept that while both physical and chemical (ADP) mechanisms are substantially involved in potentiation by RBC of SIPAG, RBC support SIPAD largely by enhancement of platelet transport from the bulk flow to the bounding surfaces. The findings also indicate that it is feasible to assess SIPAD and SIPAG in the same flow system simultaneously. A less complicated version of the method described here should prove useful in the evaluation of patients with platelet functional disorders, and in the evaluation and monitoring of antiplatelet agents.


Dipeptidyl peptidase 9 enzymatic activity influences the expression of neonatal metabolic genes.
The success of dipeptidyl peptidase 4 (DPP4) inhibition as a type 2 diabetes therapy has encouraged deeper examination of the post-proline DPP enzymes. DPP9 has been implicated in immunoregulation, disease pathogenesis and metabolism. The DPP9 enzyme-inactive (Dpp9 gene knock-in; Dpp9 gki) mouse displays neonatal lethality, suggesting that DPP9 enzyme activity is essential in neonatal development. Here we present gene expression patterns in these Dpp9 gki neonatal mice. Taqman PCR arrays and sequential qPCR assays on neonatal liver and gut revealed differential expression of genes involved in cell growth, innate immunity and metabolic pathways including long-chain-fatty-acid uptake and esterification, long-chain fatty acyl-CoA binding, trafficking and transport into mitochondria, lipoprotein metabolism, adipokine transport and gluconeogenesis in the Dpp9 gki mice compared to wild type. In a liver cell line, Dpp9 knockdown increased AMP-activated protein kinase phosphorylation, which suggests a potential mechanism. DPP9 protein levels in liver cells were altered by treatment with EGF, HGF, insulin or palmitate, suggesting potential natural DPP9 regulators. These gene expression analyses of a mouse strain deficient in DPP9 enzyme activity show, for the first time, that DPP9 enzyme activity regulates metabolic pathways in neonatal liver and gut.


Application of Artificial intelligence in COVID-19-related geriatric care: A scoping review.
Older adults have been disproportionately affected by the COVID-19 pandemic. This scoping review aimed to summarize the current evidence of artificial intelligence (AI) use in the screening/monitoring, diagnosis, and/or treatment of COVID-19 among older adults. The review followed the Joanna Briggs Institute and Arksey and O'Malley frameworks. An information specialist performed a comprehensive search from the date of inception until May 2021, in six bibliographic databases. The selected studies considered all populations, and all AI interventions that had been used in COVID-19-related geriatric care. We focused on patient, healthcare provider, and healthcare system-related outcomes. The studies were restricted to peer-reviewed English publications. Two authors independently screened the titles and abstracts of the identified records, read the selected full texts, and extracted data from the included studies using a validated data extraction form. Disagreements were resolved by consensus, and if this was not possible, the opinion of a third reviewer was sought. Six databases were searched , yielding 3,228 articles, of which 10 were included. The majority of articles used a single AI model to assess the association between patients' comorbidities and COVID-19 outcomes. Articles were mainly conducted in high-income countries, with limited representation of females in study participants, and insufficient reporting of participants' race and ethnicity. This review highlighted how the COVID-19 pandemic has accelerated the application of AI to protect older populations, with most interventions in the pilot testing stage. Further work is required to measure effectiveness of these technologies in a larger scale, use more representative datasets for training of AI models, and expand AI applications to low-income countries.


Early development of arterial spin labeling to measure regional brain blood flow by MRI.
Two major avenues of work converged in the late 1980's and early 1990's to give rise to brain perfusion MRI. The development of anatomical brain MRI quickly had as a major goal the generation of angiograms using tricks to label flowing blood in macroscopic vessels. These ideas were aimed at getting information about microcirculatory flow as well. Over the same time course the development of in vivo magnetic resonance spectroscopy had as its primary goal the assessment of tissue function and in particular, tissue energetics. For this the measurement of the delivery of water to tissue was critical for assessing tissue oxygenation and viability. The measurement of the washin/washout of "freely" diffusible tracers by spectroscopic based techniques pointed the way for quantitative approaches to measure regional blood flow by MRI. These two avenues came together in the development of arterial spin labeling (ASL) MRI techniques to measure regional cerebral blood flow. The early use of ASL to measure brain activation to help verify BOLD fMRI led to a rapid development of ASL based perfusion MRI. Today development and applications of regional brain blood flow measurements with ASL continues to be a major area of activity.


Human brain mass: similar body composition associations as observed across mammals.
A classic association is the link between brain mass and body mass across mammals that has now been shown to derive from fat-free mass (FFM) and not fat mass (FM). This study aimed to establish for the first time the associations between human brain mass and body composition and to compare these relations with those established for liver as a reference organ. Subjects were 112 men and 148 women who had brain and liver mass measured by magnetic resonance imaging with FM and FFM measured by dual-energy X-ray absorptiometry. Brain mass scaled to height (H) with powers of ≤0.6 in men and women; liver mass and FFM both scaled similarly as H(~2) . The fraction of FFM as brain thus scaled inversely to height (P < 0.001) while liver mass/FFM was independent of height. After controlling for age, brain, and liver mass were associated with FFM while liver was additionally associated with FM (all models P ≤ 0.01). After controlling for age and sex, FFM accounted for ~5% of the variance in brain mass while levels were substantially higher for liver mass (~60%). Brain mass was significantly larger (P < 0.001) in men than in women, even after controlling for age and FFM. As across mammals, human brain mass associates significantly, although weakly, with FFM and not FM; the fraction of FFM as brain relates inversely to height; brain differs in these relations from liver, another small high metabolic rate organ; and the sexual dimorphism in brain mass persists even after adjusting for age and FFM.


Alkaline labilization of DNA photosensitized by promazine derivatives.
Superhelical pBR322 DNA has been photosensitized in the presence of various promazine derivatives. Agarose gel electrophoresis of the photosensitized DNA reveals that true single-strand breaks are induced during irradiation. Alkaline treatment of the photosensitized DNA with a subsequent alkaline agarose gel electrophoresis demonstrates that in addition to true single-strand breaks, these drugs can induce alkali-labile lesions. Although true single-strand breaks are induced randomly into a 5'-[32P]-end labeled pBR322 DNA fragments, the alkaline-labile alterations are located specifically at the level of guanine residues. A strong correlation seems to exist between the visualization of this labilization and the induction of a covalent photoadduct on guanine by the photosensitization mediated by PZ.


Permanent Bulbar Urethral Ligation: Emerging Treatment Option for Incontinent Men With End-stage Urethra.
To report our experience with permanent urethral ligation for severe incontinence among men with end-stage urethra. From our institutional artificial urinary sphincter database of 512 patients from 2010 to 2016, 10 men underwent permanent urethral ligation with concurrent suprapubic tube diversion following recurrent artificial urinary sphincter cuff erosion. Clinical characteristics and outcomes were evaluated. Quality of life was assessed using the Michigan Incontinence Symptom Index and the Patient Global Index of Improvement. Urethral ligation resulted in resolution of incontinence in 8 men (80%), including 7 (70%) after 1 surgery and in 1 (10%) after a single revision. The average American Society of Anesthesiologists physical status rating was 2.7 (range 2-3). Seven patients (70%) experienced postoperative complications (4 Clavien-Dindo grade II complications [1 Clostridium difficile infection, 3 refractory bladder spasms) and 5 grade III complications (2 abscesses, 2 urethrocutaneous fistula, and 1 bladder stone formation]). Overall, satisfactory Michigan Incontinence Symptom Index urinary scores were reported in 8 (80%) men. On the Patient Global Index of Improvement, 6 (60%) men reported improvement in overall condition following surgery. All men (10/10) stated that they would recommend this procedure to others. For debilitated men with end-stage urethra and severe refractory stress urinary incontinence, permanent urethral ligation with chronic suprapubic tube drainage can restore continence and improve quality of life without the need for more invasive formal urinary diversion, though with a high risk of complication.


Educational delay and attainment in persons with neurofibromatosis 1 in Denmark.
Most research on psychosocial consequences of neurofibromatosis type 1 (NF1) has focused on the relationship between disease factors and cognitive functioning. NF1 may impair domains of learning and attention, resulting in low academic performance. This study is the first nationwide population-based cohort study to investigate educational attainment and delay in completing mandatory school by persons with NF1. Educational information was collected from 550 persons at the age of 30 (born 1965-1984). They were diagnosed with NF1 in Denmark and compared to a cohort of NF1-free persons matched on gender and age (n = 4295). Multinomial logistic models were applied to estimate odds ratios (ORs) for obtaining short (≤9 years) or medium (10-12 years) education compared to long education (>12 years) by the age of 30 years. We calculated the probability of graduating 9th year of mandatory school at different ages in 932 persons with NF1 and 7962 NF1-free persons (born 1965-2000) using quantile regression. The OR of educational completion for short- and medium-term education was three fold (95% CI 2.55-3.99) and 1.29 fold (95% CI 0.99-1.69) higher, respectively, for persons with NF1 than NF1-free persons after adjusting for birth year, gender, psychiatric and somatic morbidity and mother's education. Persons with NF1 were significantly delayed in graduating mandatory school education compared to NF1-free persons. When 90% of persons have graduated, persons with NF1 were 1.2 times older than the NF1-free persons. Experiencing delays in mandatory school likely affect further educational achievements and may impair employment and entering work force.


Aberrant methylation of E-cadherin and H-cadherin genes in nonsmall cell lung cancer and its relation to clinicopathologic features.
Lung cancer is the leading cause of cancer deaths worldwide. The epigenetic inactivation of certain genes by aberrant promoter methylation plays an important role in the pathogenesis of lung cancer. In addition, DNA hypermethylation is an extremely promising cancer marker. Cadherins are cell adhesion molecules that modulate the epithelial phenotype and regulate tumor invasion. Although the aberrant methylation of E-cadherin (CDH1) or H-cadherin (CDH13) genes has been reported in lung cancer, to the authors' knowledge, the relation between the concurrent hypermethylation in E-cadherin and H-cadherin has not been explored to date. The authors investigated the methylation status of the promoter region of human E-cadherin and H-cadherin genes in resected samples of primary nonsmall cell lung cancer (NSCLC) using methylation-specific polymerase chain reaction (MSP) analysis and correlated the results with clinicopathologic characteristics. The methylation status of the promoter regions of the E-cadherin and H-cadherin genes was examined by using nested MSP in 88 primary lung cancers and paired adjacent normal tissues. Data were compared with clinicopathologic features. The frequency of methylation in neoplastic and corresponding nonneoplastic lung tissues was 30 of 88 tissue samples (34.1%) and 5 of 88 tissue samples (5.7%) for E-cadherin and 26 of 88 tissue samples (29.5%) and 7 of 88 tissue samples (8%) for H-cadherin, respectively. In addition, in 9 patients (10.2%), both genes were methylated. Although there was no significant difference in the overall survival of patients according to the methylation pattern of the E-cadherin gene alone or the H-cadherin gene alone, patients with NSCLC who had hypermethylation of both genes had a significantly longer overall survival. However, no correlation was observed between their methylation status and any other clinicopathologic factors. The current findings suggested that simultaneous methylation of the E-cadherin and H-cadherin genes occurs in a subset of NSCLCs and may be used as a prognostic marker for patients with NSCLC. However, further studies with large numbers of patients will be needed to confirm the findings.


Knockdown of TRPM2 promotes osteogenic differentiation of human periodontal ligament stem cells by modulating NF-κB /NLRP3 pathway.
Periodontitis is characterized by periodontal destruction triggered by chronic inflammation. The optimal treatment for periodontitis is to improve the periodontal microenvironment, reduce inflammation and achieve periodontal regeneration. Recently, the role of TRPM2 in inflammatory diseases has been reported. However, the function of TRPM2 in periodontal disease and the biological mechanism remain elusive. Therefore, this study aimed to identify the role and explore the underlying mechanisms of TRPM2 in periodontal disease. Here, we first identified the characterization of human periodontal ligament stem cells (PDLSCs). Oil Red O Staining and Alizarin Red mineralized matrix were used to evaluate the multi-differentiation capacity of cells. Flow cytometry was employed to detect MSC-specific surface markers of hPDLSCs. hPDLSCs were treated with 0, 5, 10 or 40 μg/mL of TNF-α for 72 h. Western blot assay were performed to examine the expression of Transient receptor potential cation channel, subfamily M, member 2 (TRPM2) in hPDLSCs. CCK8 and colony formation assays were used to detect the cell viability and proliferation of hPDLSCs, which revealed that TRPM2 knockdown promoted hPDLSCs proliferation. Then, ALP activity in hPDLSCs was detected by ALP activity detection kit. Next, the expression of ALP and Runx2 in hPDLSCs was detected by immunofluorescence staining. The result showed that TRPM2 knockdown promoted osteogenic differentiation and affected the genes expression of osteogenic. Finally, the expressions of p-p65, p65, p-IκBα, IκBα and NLRP3 in hPDLSCs were detected by western blot assay. Together, these results suggested that knockdown of TRPM2 accelerated osteogenic differentiation of hPDLSCs through mediating NF-κB /NLRP3 pathway.


Gastrointestinal illnesses and their effects on the oral cavity.
Many disease processes affecting the gastrointestinal (GI) tract may cause observable changes to the oral cavity. In fact, oral cavity changes may represent the first clinical manifestation of an underlying GI condition. Recognition and appropriate referral of a possible GI condition contribute to overall health and wellness in patients. Some of the more important GI conditions that may manifest oral cavity involvement include: reflux disorders, inherited GI polyposis syndromes, and inflammatory bowel disease. This article briefly reviews the aforementioned topics.


"Regulating" rheumatoid arthritis via autotransplantation.
Using a mouse model of inducible autoimmune arthritis that mimics some aspects of the human disease, Roord and colleagues identify a role for regulatory T cells (Tregs) both for modulation of disease and as a therapeutic component of autologous bone marrow transplantation (aBMT).


Amygdala inhibition impairs fear conditioning but increases the stimulus-driven activity in the inferior colliculus.
It has been shown that fear conditioning improves the steady-state evoked potentials driven by a long lasting amplitude modulated tone in the inferior colliculus. In this work we tested the hypothesis that the amygdala modulates this effect, since it plays a crucial role in assessing the biological relevance of environmental stimuli. We inhibited the basolateral nucleus of the amygdala of rats by injecting a GABAa receptor agonist (muscimol) before the recall test session of an auditory fear conditioning paradigm and recorded the evoked activity in the central nucleus of the inferior colliculus. According to our results, the treatment with muscimol decreased the expression of freezing behavior during the recall test session, but did not impair the entrainment of the evoked activity in the inferior colliculus induced by fear conditioning. We repeated the injection protocol with another group of rats but without pairing the tone to an aversive stimulus and observed that the inhibition of the basolateral amygdala enhances the stimulus-driven activity in the inferior colliculus regardless of the conditioning task. Our findings suggest that the basolateral amygdala exerts a tonic modulation over the encoding of sensory information at the early stages of the sensory pathway.


pLoc-mGneg: Predict subcellular localization of Gram-negative bacterial proteins by deep gene ontology learning via general PseAAC.
Information of the proteins' subcellular localization is crucially important for revealing their biological functions in a cell, the basic unit of life. With the avalanche of protein sequences generated in the postgenomic age, it is highly desired to develop computational tools for timely identifying their subcellular locations based on the sequence information alone. The current study is focused on the Gram-negative bacterial proteins. Although considerable efforts have been made in protein subcellular prediction, the problem is far from being solved yet. This is because mounting evidences have indicated that many Gram-negative bacterial proteins exist in two or more location sites. Unfortunately, most existing methods can be used to deal with single-location proteins only. Actually, proteins with multi-locations may have some special biological functions important for both basic research and drug design. In this study, by using the multi-label theory, we developed a new predictor called "pLoc-mGneg" for predicting the subcellular localization of Gram-negative bacterial proteins with both single and multiple locations. Rigorous cross-validation on a high quality benchmark dataset indicated that the proposed predictor is remarkably superior to "iLoc-Gneg", the state-of-the-art predictor for the same purpose. For the convenience of most experimental scientists, a user-friendly web-server for the novel predictor has been established at http://www.jci-bioinfo.cn/pLoc-mGneg/, by which users can easily get their desired results without the need to go through the complicated mathematics involved.


Should the insulin resistance syndrome be treated in the elderly?
The insulin resistance syndrome represents the co-occurrence of hyperglycaemia, hypertension, central and overall obesity, and dyslipidaemia characterised by low high density lipoprotein-cholesterol (HDL-C) and high triglyceride levels. Epidemiologic studies have revealed an increasing prevalence of the insulin resistance syndrome in elderly populations. Indeed, recent data indicate that over 40% of US adults aged > or =60 years meet current criteria for the insulin resistance syndrome. Patients with this syndrome are at increased risk for the development of both cardiovascular disease (CVD) and type 2 diabetes mellitus, two of the most significant health problems among people >65 years of age. Identification and treatment of the insulin resistance syndrome may thus represent an important approach to reducing the overall burden of morbidity and mortality in the elderly. While development of the insulin resistance syndrome is partly determined by modifiable environmental factors, there may be a genetic basis for the syndrome, with high levels of concordance among monozygotic twins. Ongoing research focusing on the pathophysiology of this syndrome has implicated insulin resistance as the central disorder underlying both the development of diabetes as well as the pro-thrombotic endothelial dysfunction characteristic of CVD. Studies aimed at reversing insulin resistance have identified weight loss, exercise and pharmacological treatment with metformin, thiazolidinediones, HMG-CoA reductase inhibitors (statins) and ACE inhibitors as potential therapies to prevent the development of type 2 diabetes. However, although insulin sensitisation may be beneficial for preventing type 2 diabetes, there are no data yet available to show whether this strategy will reduce the incidence of CVD. Increased exercise and other healthy lifestyle changes form the cornerstone of therapy for elderly patients with the insulin resistance syndrome. In addition, active identification and aggressive management of traditional cardiovascular risk factors are the current standard of care. For elderly patients, recent studies have conclusively demonstrated the safety and efficacy of pharmacological management of elevated blood pressure and cholesterol levels.


X-ray diffraction by crystals of beef heart ubiquinol: cytochrome c oxidoreductase.
Beef heart mitochondrial ubiquinol:cytochrome c oxidoreductase has been crystallized in the shape of hexagonal bipyramids. At present the crystals diffract X-rays to 4.7 A. From preliminary analysis the diffraction pattern appears to be consistent with space group P6(1)22 or P6(5)22 and with unit cell parameters a = b = 212 A and c = 352 A.


Search for a prion-specific nucleic acid.
Diversity of prion strains was attributed to an elusive nucleic acid, yet a search spanning nearly two decades has failed to identify a prion-specific polynucleotide. In our search for a prion-specific nucleic acid, we analyzed nucleic acids in purified fractions from the brains of Syrian hamsters infected with Sc237 prions. Purification of Sc237 prions removed nucleic acids larger than 50 nucleotides as measured by return refocusing electrophoresis (RRGE). To determine the size of the largest polynucleotide present in purified fractions at an abundance of one molecule per infectious (ID50) unit, we measured prions present after inoculation. In order to account for the rapid clearance of prions after intracerebral inoculation, we determined the number of PrP(Sc) molecules and ID50 units of prions that were retained in brain. Factoring in clearance after inoculation, we estimate that the largest polynucleotide present in our purified fractions at one molecule per ID50 unit is approximately 25 nucleotides in length. In the same fractions, there were approximately 3,000 protease-resistant PrP(Sc) molecules per ID50 unit after accounting for clearance of PrP(Sc) following inoculation. We compared the resistance of Sc237 and 139H prions to inactivation by UV irradiation at 254 nm. Irradiation of homogenates and microsomes diminished prion infectivity by a factor of approximately 1,000 but did not alter the strain-specified properties of the Sc237 and 139H prions. The data reported here combined with the production of synthetic prions argue that the 25-mer polynucleotides found in purified prion preparations are likely to be host encoded and of variable sequence; additionally, these 25-mers are unlikely to be prion specific.


Non-hyalinizing trabecular thyroid adenoma: a novel thyroid tumor with diagnostic pitfalls of hyalinizing trabecular adenoma and medullary thyroid carcinoma.
Only one thyroid follicular cell-derived tumor with a purely trabecular growth pattern has previously been described. This report aims to describe the histological, immunohistochemical, and molecular findings of our second case, propose a novel thyroid tumor, and discuss its diagnostic pitfalls. A 68-year-old female presented with an encapsulated thyroid tumor composed of thin and long trabeculae. No papillary, follicular, solid, or insular patterns are observed. The tumor cells were elongated or fusiform and arranged perpendicular to the trabecular axis. No nuclear findings of papillary thyroid carcinoma and increased basement membrane material were found. Immunohistochemically, the tumor cells were positive for paired-box gene 8, thyroid transcription factor-1, and negative for thyroglobulin, calcitonin, and chromogranin A. Inter- and intra-trabecular accumulation of type IV collagen-positive materials was not demonstrated. None of PAX8/GLIS1 and PAX8/GLIS3 and mutations in BRAF, HRAS, KRAS, NRAS, TERT promoter, CTNNB1, PTEN, and RET were detected. We report our case as a novel disease entity called non-hyalinizing trabecular thyroid adenoma, which has the diagnostic pitfalls of hyalinizing trabecular tumor and medullary thyroid carcinoma.


Primary peritoneal serous carcinoma: a primer for radiologists.
Primary peritoneal serous carcinoma (PPSC) is a rare primary peritoneal tumor characterized by a unique range of clinical features and imaging findings. Though it shares many clinical, histologic, and imaging features with serous ovarian carcinoma, it remains a distinct clinical entity. Although less common than its primary ovarian counterpart, PPSC is characterized by a prognosis that is often equally poor with presentations common in late stages of disease. Key imaging modalities used in the evaluation of PPSC include ultrasound, CT, MRI, and PET/CT. For radiologists, an understanding of the pertinent imaging findings, pathologic correlations, and clinical features of PPSC is essential for arriving at the correct diagnosis and guiding the subsequent appropriate management of this complex malignancy.


Clarity and causality needed in claims about Big Gods.
We welcome Norenzayan et al.'s claim that the prosocial effects of beliefs in supernatural agents extend beyond Big Gods. To date, however, supporting evidence has focused on the Abrahamic Big God, making generalisations difficult. We discuss a recent study that highlights the need for clarity about the causal path by which supernatural beliefs affect the evolution of big societies.


Inverted papilloma: a follow-up study including primarily unacknowledged cases.
Inverted papillomas (IPs) in the nose or the paranasal sinuses exhibit a tendency for rapid growth with bone destruction, a high recurrence rate, and an association with malignancy, requiring early diagnosis and aggressive surgical therapy. A number of operative approaches have been reported in the literature, with greatly varying results. Furthermore, the incidence of IP and the association with carcinoma are not well-established. In this study, we present a series of 42 patients with IP. Drawing from the resources of two institutes of pathology, we reviewed all specimens of nasal cavity or paranasal sinus tissue taken between the years 1975 and 1986, and performed a thorough follow-up of all IP patients. The incidence was found to be 0.6 cases per 100,000 inhabitants per year in a well-defined representative geographic region. Two patients had concomitant carcinoma. When the initial surgical approach was lateral rhinotomy, the recurrence rate was 50%. This was not significantly different from that noted following excision through a sinusectomy (62%) or simple endonasal excision (43%). However, initial procedures were selected individually, mainly on the basis of tumor size and location. Accordingly, a limited procedure is considered justified even in cases with lateral lesions, if the tumor is sufficiently visible and confined. In other cases, lateral rhinotomy is required. Septal IPs are often detected at an early stage and are therefore often amenable to local excision.


Assessment of soil- and water-related ecosystem services with coupling the factors of climate and land-use change (Example of the Nitra region, Slovakia).
Climate and land use change can profoundly impact the provision of ecosystem services (ES) over time, particularly in the landscape of open fields along with growing urbanization and rising demand for space, food and energy. Policymakers are keen on knowing the combined effects of climate and land use change on ESs as a critical issue in human well-being. However, deep knowledge of how to identify these relationships is still lacking. This research aims to undertake a comprehensive assessment of soil- and water-related ES, and improvement in understanding how they are affected by climate and land use change. We applied the Integrated Valuation of Ecosystem Services and Trade-offs model for four ES (soil retention, nutrient delivery ratio, carbon storage, and water yield) for the years 2000 and 2018 in the Nitra region, Slovakia. We investigated the spatial and temporal changes in ES provision and determined the hotspots and coldspots of multiple ES. We found that soil retention, water yield, and carbon storage display a rising trend while the nutrient delivery ratio showed a decreasing trend over the past 18 years. Although all the mentioned services mainly attributed to land use change, the relative contribution of climate change was not deniable. Forests in the north and east and distributed urbanization and agriculture are the hotspots and coldspots for all ESs, respectively. Our results, in terms of determining the relative importance of land use and climate change and identifying the sensitive areas of ES provision, provide a scientific basis for ecosystem conservation and management priority setting at the local and regional levels.


Biochar-supported sulfurized nanoscale zero-valent iron facilitates extensive dechlorination and rapid removal of 2,4,6-trichlorophenol in aqueous solution.
Nanoscale zero-valent iron (NZVI) has been widely used in rapid remediation of contaminants. However, several obstacles such as aggregation and surface passivation hampered NZVI from further application. In this study, sulfurized nanoscale-zero valent iron supported by biochar (BC-SNZVI) was successfully synthesized and utilized for highly efficient 2,4,6-trichlorophenol (2,4,6-TCP) dechlorination in aqueous solution. SEM-EDS analysis revealed the even distribution of SNZVI on the surface of BC. FTIR, XRD, XPS and N2 Brunauer-Emmett-Teller (BET) adsorption analyses were carried out to characterize the materials. Results showed that BC-SNZVI with S/Fe molar ratio of 0.088, Na2S2O3 as sulfurization agent, and pre-sulfurization as the sulfurization strategy exhibited the superior performance for 2,4,6-TCP removal. The overall removal of 2,4,6-TCP was well described with the pseudo-first-order kinetics (R2 > 0.9), and the observed kinetics constant Kobs was 0.083 min-1 with BC-SNZVI, which was one order of magnitude higher than that of BC-NZVI (0.0092 min-1) and SNZVI (0.0042 min-1), and two orders of magnitude higher than that of NZVI (0.00092 min-1). Moreover, the removal efficiency of 2,4,6-TCP reached 99.5% by BC-SNZVI with dosage of 0.5 g L-1, initial 2,4,6-TCP concentration of 30 mg L-1 and initial solution pH of 3.0 within 180 min. The removal of 2,4,6-TCP by BC-SNZVI was acid-promoted and the removal efficiencies of 2,4,6-TCP decreased with the increase of initial 2,4,6-TCP concentrations. Furthermore, more extensive dechlorination of 2,4,6-TCP was achieved with BC-SNZVI and complete dechlorination product phenol became predominant. The facilitation of sulfur for Fe0 utilization and electron distribution in the presence of biochar remarkably enhanced the dechlorination performance of BC-SNZVI for 2,4,6-TCP. These findings provide insights into BC-SNZVI as an alternative engineering carbon based NZVI material for treating chlorinated phenols.


Utility of targeted glucocorticoids in cancer therapy.
Glucocorticoids can inhibit solid tumor growth via downregulation of tumor-associated inflammation/angiogenesis. In this minireview we describe the possible mechanisms of glucocorticoid action in tumor growth inhibition. We also present an overview of the current status of tumor-targeted glucocorticoid delivery. It appears that long-circulating liposomes are the only targeting system currently being explored for this purpose.


Photocurable high internal phase emulsions (HIPEs) containing hydroxyapatite for additive manufacture of tissue engineering scaffolds with multi-scale porosity.
Porous composites containing hydroxyapatite (HA) were templated from high internal phase emulsions (HIPEs) and were further structured using direct-write UV stereolithography to produce composite scaffolds with multi-scale porosity. FTIR, TGA and SEM analyses confirmed that HA was retained after photocuring and subsequent treatments and was incorporated within the polymerised HIPE (polyHIPE). The addition of HA particles to the polyHIPE caused changes in the mechanical properties of the material. An increase in both the Young's modulus and maximum stress at yield was observed compared with the pure polyHIPE from 1.544±0.231 to 4.614±0.775 and 0.177±0.009 to 0.267±0.034MPa, respectively. Except at very high concentrations, adding HA did not adversely cause the phase separation of the HIPE or the porous microstructure of the resulting polyHIPE. In combination with a photoinitiator, the HIPE emulsion containing HA was investigated as a photocurable resin for stereolithography-based additive manufacturing. The material was readily processable into "woodpile" structures via direct-write UV stereolithography, producing scaffolds with multi-scale porosity which may be useful for medical applications such as tissue engineering. In conclusion, HA was successfully added into polyHIPEs, producing a similar porous structure to that of the pure polyHIPE whilst improving the mechanical performance.


The effect of age, sex, and lifestyle factors on micronucleus frequency in peripheral blood lymphocytes of the Bosnian population.
This study confirmed that the frequency of human lymphocyte biomarkers measured with the cytokinesis-block micronucleus cytome (CBMNcyt) assay, is associated with age, sex, and lifestyle factors. Cytogenetic analysis was carried out on samples from 100 healthy individuals living in Bosnia and Herzegovina. Cells were cytologically scored for viability status, defined by the proportion of necrotic and apoptotic cells; mitotic status, corresponding to the proportion and ratios of mono-, bi- and multinucleated cells; the nuclear division index and chromosomal damage, determined by the presence of micronuclei, nucleoplasmic bridges or nuclear buds of bi-nucleated cells. Ageing is positively associated with the frequency of cytogenetic biomarkers. The micronucleus frequency in females was significantly higher than the micronucleus frequency in males. The micronucleus frequency is positively associated with family history of cancer. Furthermore, it is positively correlated with smoking: the frequency is higher in male subjects with a smoking habit than in female smokers. However, alcohol is observed to decrease the frequency of apoptotic cells in human lymphocytes. The frequency of micronuclei was positively correlated with exposure to medication. Lastly, the frequency of nuclear buds and apoptotic and necrotic cells negatively correlated with exposure to radiation.


[The construction of transferrin receptor- mediated HSV-TK gene transfer system and its effect on human hepatocellular carcinoma cells in vitro].
To construct the localization system involving anti-TfR monoclonal antibody (McAb) and AFP promoters and assess its effect on human hepatoma cell lines. The conjugate of anti-TfR McAb and polylysine (PLL) was made by SPDP and purified by molecular screen chromatography. DNA blocking test determined that the ratio of one pEBAF/tk to six Ab-PLL was the most suitable to couple them. The pEBAF/tk recombinant plasmid bearing HSV-TK gene was coupled to Ab-PLL by noncovalent bond. The pEBAF/tk was transferred into human hepatoma cell line HepG2, SMMC7721 and pulmonary cancer cell line A549 by receptor-mediated gene delivery (Ab-PLL-DNA) and liposome procedure. The growth inhibitory rates of HepG2, SMMC7721 and A549 cells were measured by MTT assay. The inhibitory rates of HepG2/tk in 100 mg/L and 1 mg/L of GCV were 60.5% and 24.3%, respectively. The inhibitory rate of GCV to SMMC7721 was 23.2% in 3 days. The pulmonary cancer cell A549, A549/tk (Ab) and A549 /tk (lipo) could not be inhibited by the addition of GCV. The localization system employed in this paper has high specificity, effectiveness and safety for gene therapy. It would be a promising strategy for gene therapy.


Synthesis of water soluble bis-triazenoquinazolines: an unusual predicted mode of binding to the epidermal growth factor receptor tyrosine kinase.
A novel type of 3,3-disubstituted bis-triazenes containing an ethylaminoethyl linker flanked by two identical anilinoquinazoline ring was synthesized. These model molecules contained an N-ethylaminomorpholine moiety designed to enhance water solubility. Despite their significant bulkiness, they blocked epidermal growth factor receptor (EGFR) tyrosine kinase in a dose-dependent manner with IC(50) values in low micromolar range. Molecular modeling to predict the interactions of the molecule with the ATP binding site of EGFR suggests that the N-ethylaminomorpholine side chain plays a binding role.


Geranyl and neryl triazole bisphosphonates as inhibitors of geranylgeranyl diphosphate synthase.
When inhibitors of enzymes that utilize isoprenoid pyrophosphates are based on the natural substrates, a significant challenge can be to achieve selective inhibition of a specific enzyme. One element in the design process is the stereochemistry of the isoprenoid olefins. We recently reported preparation of a series of isoprenoid triazoles as potential inhibitors of geranylgeranyl transferase II but these compounds were obtained as a mixture of olefin isomers. We now have accomplished the stereoselective synthesis of these triazoles through the use of epoxy azides for the cycloaddition reaction followed by regeneration of the desired olefin. Both geranyl and neryl derivatives have been prepared as single olefin isomers through parallel reaction sequences. The products were assayed against multiple enzymes as well as in cell culture studies and surprisingly a Z-olefin isomer was found to be a potent and selective inhibitor of geranylgeranyl diphosphate synthase.


[Advanced practice nurse, a growing status].
Present throughout the country, nurses are a considerable asset in a context of medical desertification. It is therefore important to rethink the healthcare system by questioning the central place of doctors in the care pathway and by opening the way for direct access to other professionals, such as advanced practice nurses (APN). The year 2023 saw a change in this direction, with the passage of the Rist bill on improving access to care. This bill opens direct access to APNs working in coordinated practice structures and announces the implementation of an experiment in six departments on direct access to APNs working in territorial professional health communities.


Lower facial regeneration with a combination of platelet-rich fibrin liquid matrices based on the low speed centrifugation concept-Cleopatra technique.
Autologous blood concentrates are increasingly being applied in esthetic medicine and dentistry due to their safety and their potential beneficial properties. Platelet-rich fibrin based on the low speed centrifugation, a newly described blood product, seems to convey additional properties in several in vitro and ex vivo studies. Its clinical significance however in relation to facial regeneration remains anecdotal. The aim of this study was to assess a specific combination of PRF liquid matrices utilized for lower facial regeneration (Cleopatra technique). Cleopatra technique was applied in 32 patients. In addition to recording of all patients' complaints and adverse events, a photographical study was performed. Possible positive effects were assessed by asking twenty-three independent reviewers to distinguish initial and later photographs of each patient. A statistically significant percentage of true answers by the reviewers was noted upon completion of the treatment (U = 110.5, P < .001), which indicates a clinically significant effect of Cleopatra technique. Moreover, only few minor, self-limited adverse events were recorded. Cleopatra technique is a well-tolerated and effective method of lower facial rejuvenation that deserves further attention from dentists and other health professional who utilize conservative methods in facial esthetics.


Mononuclear and Dinuclear Ruthenium Complexes of cis- and trans-Thioindigo: Geometrical and Electronic Structure Analyses.
The compounds [Ru(acac)2(L)] (1) and [Ru2(acac)4(μ-L)] (2) with acac- = acetylacetonato and L = thioindigo were characterized crystallographically with a cis-configurated L and O,O'-coordinated metal in 1 and with trans-configurated L and two S,O-coordinated bridged ruthenium centers for 2. The electronic structures of 1 and 2 were confirmed by spectroscopy and density functional theory calculations, suggesting considerable metal-to-ligand electron transfer resulting in the formation of the thioindigo radical anion and oxidized metal(s). UV-Vis-Near-IR and IR (spectro)electrochemistry was used to investigate charged forms 1 n ( n = 1+, 1-) and 2 n ( n = 1+, 1-, 2-), which reveal electron transfer activity of both the metal and the thioindigo ligand as well as sizable orbital mixing. An intense near-IR absorption is observed for 2- at 2180 nm. The remarkable ligand properties of thioindigo are being discussed in connection to related coordination compounds of indigo derivatives such as dehydroindigo and corresponding ("Nindigo") diimines.


Multiple congenital hemangiopericytomas of the head and neck.
Hemangiopericytoma is a vascular tumor arising from contractile cells, the pericyte of Zimmermann. The neoplasms most frequently involve deep musculature; however, 16% occur in the head and neck region. The case presented here represents the rare occurrence of multiple congenital hemangiopericytoma of the head and neck. In older patients, these rather poorly differentiated tumors recur locally after excision in 50%-80% of cases depending on the organ site involved. Distant metastasis to lung or bone may follow. Congenital hemangiopericytomas appear to follow a more benign clinical course, possibly due to a more superficial location and a tendency to transform into hemangioendotheliomas. Recommended treatment is wide local excision and long-term follow-up.


Preparation, multi-scale structures, and functionalities of acetylated starch: An updated review.
Acetylated starch has been widely used as food additives. However, there was limited information available regarding the impact of acetylation on starch structure and functionalities, as well as the advanced acetylation technologies. This review aimed to summarize current methods for starch acetylation and discuss the structure and functionalities of acetylated starch. Innovative techniques, such as milling, microwave, pulsed electric fields, ultrasonic, and extrusion, could be employed for environmental-friendly synthesis of acetylated starch. Acetylation led to the degradation of starch structures and weakening of the interactions between starch molecules, resulting in the disorganization of starch multi-scale ordered structure. The introduction of acetyl groups retarded the self-reassembly behavior of starch, leading to increased solubility, clarity, and softness of starch-based hydrogels. Moreover, the acetyl groups improved water/oil absorption capacity, emulsifiability, film-forming properties, and colonic fermentability of starch, while reduced the susceptibility of starch molecules to enzymes. Importantly, starch functionalities were largely influenced by the decoration of acetyl groups on starch molecules, while the impact of multi-scale ordered structures on starch physicochemical properties was relatively minor. These findings will aid in the design of structured acetylated starch with desirable functionalities.


Citrobacter amalonaticus human urinary tract infections, Marseille, France.
Citrobacter amalonaticus is a bacterium that has rarely been reported as a human pathogen. Here we report four cases of C. amalonaticus infections occurring in patients hospitalized in Marseille, France, and review all cases described in the published literature.


Effects of propofol and surgery on neuropathology and cognition in the 3xTgAD Alzheimer transgenic mouse model.
Previous work suggests that anaesthesia and surgery amplify the pathology and cognitive impairment of animals made vulnerable via age or specific transgenes. We hypothesized that surgery under propofol anaesthesia, a widely used i.v. general anaesthetic, has minimal delayed cognitive and neuroinflammatory sequelae in a vulnerable mouse transgenic model. We conducted caecal ligation and excision surgery in cognitively presymptomatic (11-month-old) 3xTgAD mice under i.p. propofol anaesthesia. Age-matched 3xTgAD control mice received vehicle or propofol without surgery. Morris water maze testing was conducted 3 and 15 weeks later. Brains were examined with quantitative immunohistochemistry for amyloid β plaques, tau pathology, and microglial activation. Acute changes in neuroinflammatory cytokines were assessed in separate cohorts at 6 h. We detected no significant differences between groups in escape latencies at either 3 or 15 weeks, but detected a significant effect of surgery in the probe test at both 3 and 15 weeks. Spatial working memory was unaffected at 16 weeks in any group. No effects of either propofol alone or propofol with surgery were detected on plaque formation, tau aggregates, or neuroinflammation. Acute biochemical assays detected no effects in brain interleukin-10 or interleukin-6 concentrations. Surgery in a vulnerable transgenic mouse under propofol anaesthesia was associated with minimal to no changes in short- and long-term behaviour and no changes in neuropathology. This suggests that propofol anaesthesia is associated with better cognitive outcomes in the aged, vulnerable brain compared with inhalation anaesthesia.


Dermatitis artefacta.
An unusual case of dermatitis artefacta is presented. The patient lost the whole of the index finger of his dominant hand before the diagnosis was established. The motive was financial gain. The literature on self-inflicted disease is reviewed.


Rods affect S-cone discrimination on the Farnsworth-Munsell 100-hue test.
Rod influence on hue discrimination was assessed by the Farnsworth-Munsell 100-hue test. Rod influence was taken as the difference in error scores obtained after complete dark adaptation and during the cone plateau at three mesopic (23, 9, 3 td) and one standard (158 td) light level. On the FM 100, rods produced a differential discrimination loss along a tritan axis as compared with a red-green axis without any bias toward a rod confusion axis. Rods appear to impair discrimination mediated by S-cone pathways, which at moderate levels of illumination can differentially elevate tritan errors on the FM 100.


Apparent diffusion coefficient correlation with oesophageal tumour stroma and angiogenesis.
Because diffusion-weighted imaging (DWI) can predict the prognosis of patients with oesophageal squamous cell carcinoma (ESCC), we hypothesised that apparent diffusion coefficient (ADC) values might be correlated with the collagen content and tumour angiogenesis. The purpose of this study was to determine the correlation between ADC values of ESCC before treatment and oesophageal tumour stroma and angiogenesis. Seventeen patients with ESCC were enrolled. The ADC values were calculated from the DWI score. Seventeen patients who had undergone oesophagectomy were analysed for tumour stroma, vascular endothelial growth factor (VEGF) and CD34. Tissue collagen was stained with azocarmine and aniline blue to quantitatively analyse the extracellular matrix in cancer stroma. Tissues were stained with VEGF and CD34 to analyse the angiogenesis. The ADC values decreased with stromal collagen growth. We found a negative correlation between the tumour ADC and the amount of stromal collagen (r = -0.729, P = 0.001), i.e. the ADC values decreased with growth of VEGF. We also found a negative correlation between the ADC of the tumours and the amount of VEGF (r = 0.538, P = 0.026). Our results indicated that the ADC value may be a novel prognostic factor and contribute to the treatment of oesophageal cancer. • Magnetic resonance apparent diffusion coefficient values inversely indicate tumour stromal collagen • There is also negative correlation between ADCs and vascular endothelial growth factor • ADC values may contribute to the treatment of oesophageal cancer.


Executive control functions in degenerative dementias: a comparative review.
This paper reviews the literature concerning executive control impairments in degenerative dementias. The construct of executive control functioning is examined, as is the neuroanatomy of frontal-subcortical networks, believed to underlie executive function (EF) impairments. The pattern of EF impairments in Alzheimer's disease (AD) which affects temporal and parietal brain regions most severely is contrasted with observed executive dysfunctions in patients with dementias involving degeneration of primarily frontal and frontal-subcortical brain areas. EF impairments are present in each of these types of dementing illnesses. Although EF impairments are present in AD, they are less prominent than the memory disorder in the neuropsychological profile of the disease and tend to become more pronounced later in the course of the illness. In contrast, patients with frontal or frontal-subcortical dementia may demonstrate executive dysfunction, which occurs earlier in the disease progression and may be initially more severe.


Direct evidence for the role of haem doming as the primary event in the cooperative transition of haemoglobin.
The study of cooperative ligand binding among the four subunits of haemoglobin has played a central role in the understanding of allosteric transitions in a large number of enzymes. Haem iron out-of-plane motion has been suggested to be the trigger for the cooperative transition of haemoglobin. To function as a trigger in a dynamic sense, haem-iron doming must be the first conformational change to occur following ligand dissociation. Here we present the first direct demonstration that haem-iron doming occurs on the same time scale as the breaking of the iron-ligand bond, thus establishing haem-iron doming as the primary event which lead to the R-->T transition in haemoglobin.


Association of valdecoxib, a nonsteroidal anti-inflammatory drug, with human serum albumin.
Valdecoxib addition quenches the intrinsic human serum albumin (HSA) fluorescence. This allows an evaluation of the drug-protein association. However, both the number of binding sites and their affinity for the drug depend upon the methodology employed for their evaluation and the employed protein concentration. In this work, we measured the effect of valdecoxib on HSA fluorescence yield over a wide range of experimental conditions and discuss the validity of the binding parameters derived from the different data treatments: Stern-Volmer, Scatchard, double logarithmic, quadratic equation, Benesi-Hilderand, and Encinas-Lissi. It is proposed that a combination of Encinas-Lissi and Scatchard treatments of the data renders the most reliable results. From these data, it is concluded that HSA presents three high-affinity binding sites for valdecoxib (K(as) = 4.5 × 10(4) m(-1)) and several secondary sites of smaller activity.


[Synthesis and expression of 42 kD C-terminal region of the major merozoite surface protein (MSP1 - 42) of P. falciparum 3D7 strain in pichia pastoris].
Production of 3D7/MSP1 - 42 recombinant protein with correct conformation in Pichia pastoris for vaccine efficiency assay. Asymmetric PCR-based method was utilized to synthesize the 1 202 bp 3D7/msp1 - 42 gene. The expressing plasmid containing the synthetic gene was introduced into Pichia pastoris by electroporation. The secreted product was detected by Western Blot. The redesigned entire 3D7/msp1 - 42 gene was generated with error-free, and expressed to produce 42 kD recombinant protein in secreted form. Conformational monoclonal antibody specific for MSP1 C-terminal can interact with the recombinant protein. The redesigned 3D7/msp1 - 42 gene was expressed in P. pastoris with full length of recombinant protein which resembled most likely to the native protein.


Immunohistochemical study of carcinoembryonic antigen (CEA) in gastric tumors: correlation with preoperative serum levels, histologic type, and grade of anaplasia of the tumor.
The occurrence of carcinoembryonic antigen (CEA) was studied in 45 cases of gastric tumors by the immunoperoxidase technique. CEA-positive staining was found in 48.8% of tumors. A correlation was found between preoperative CEA values and tumor CEA staining. All patients with serum CEA values below 2.5 ng/ml showed CEA-negative staining of tumor. In patients with serum CEA values between 2.6 and 10 ng/ml, the tumors showed a minority of CEA-positive cells; but in patients with serum CEA values above 10 ng/ml, the tumors contained a majority of CEA-positive cells. CEA-positive staining was found in 34.4% of tumors of the diffuse type, and in 75% of tumors of the intestinal type. A high percentage of CEA positivity was seen in well-differentiated tumors (87.7%) compared to the moderately differentiated (69.2%), and to the undifferentiated (28.7%). A faint CEA-positivity was observed in intestinal metaplasia, while normal gastric mucosa was CEA-negative.


Association of ITPKC gene polymorphisms rs28493229 and rs2290692 in North Indian children with Kawasaki disease.
Single-nucleotide polymorphisms (SNPs) of several genes are linked to the etiopathogenesis of Kawasaki disease (KD). Association of SNPs of inositol 1,4,5-triphosphate-3-kinase C (ITPKC) gene with susceptibility to KD and coronary artery lesions (CALs) has been observed in children of certain ethnicities, but not from others. The present study was planned to explore this genetic association in the North Indian cohort. Fifty children with KD and 50 age- and sex-matched controls were studied for two SNPs (rs28493229 and rs2290692) of the ITPKC gene using polymerase chain reaction and restriction fragment length polymorphism. Findings were confirmed by Sanger sequencing. A meta-analysis was also carried out for GG and CC genotypes of the SNPs. There was significant association between KD susceptibility and CG + GG genotype of rs2290692 (p = 0.015, odds ratio = 4.1, 95% confidence interval = 1.38-13.83). None of the single alleles or genotypes of the SNPs of ITPKC were, however, significantly associated with KD susceptibility. A meta-analysis also did not show any significant association of these SNPs to KD susceptibility. Our findings suggest that ITPKC gene SNPs (rs28493229 and rs2290692) did not have a significant association with susceptibility to KD in children from North India. Larger multicentric studies incorporating different ethnicities are required to understand the genetic basis of KD. While SNP rs28493229 of the ITPKC gene is not found to be associated with susceptibility to KD, the combined genotype of SNP rs2290692 is shown to be associated. Impact of ITPKC gene SNP on KD is different across different races and ethnicities. We could find an association of the combined genotype of rs2290692 with it in the Indian population. This study highlights that phenotype and genotypic association of KD varies with ethnicities. Larger multicentric studies are required to reach a conclusion regarding the genetic association of KD.


Genetic diversity of Phytophthora colocasiae isolates in India based on AFLP analysis.
Phytophthora colocasiae that causes taro leaf blight is one of the most devastating diseases of taro which is widely distributed in India. Inter and intra-specific genetic diversity among P. colocasiae isolates collected from same field was assessed using amplified fragment length polymorphism (AFLP) marker. Seven primer pairs produced 431 markers, of which 428 (99.2 %) were polymorphic. Considerable genetic variability was displayed by the isolates. The average value of the number of observed alleles, the number of effective alleles, mean Nei's genetic diversity, and Shannon's information index were 1.993, 1.385, 0.261, and 0.420, respectively. Analysis of molecular variance (AMOVA) showed that the majority (85 %) of the diversity were present within populations of P. colocasiae. Dendrogram based on AFLP molecular data using the unweighted pair group method with arithmetic mean (UPGMA) classified the P. colocasiae isolates into two major clusters irrespective of their geographical origin. Clustering was further supported by principle coordinate analysis. Cophenetic correlation coefficient between dendrogram and original similarity matrix was significant (r = 0.816). The results of this study displayed a high level of genetic variation among the isolates irrespective of the geographical origin. The possible mechanisms and implications of this genetic variation are discussed.


Subunit organisation and symmetry of pore-forming, oligomeric pneumolysin.
We present a detailed analysis of the oligomeric subunit organisation of pneumolysin by the use of negative stain electron microscopy and image processing to produce a projection density map. Analysis of the rotational symmetry has revealed a large and variable subunit number, between 40-50. The projected subunit density by rotational averaging shows at least two distinct subunit domains at different radial positions. Side views of the rings reveal further details concerning the dimensions of the oligomer in the membrane. On the basis of these observations and our previous knowledge of the monomer domain structure we propose that the 4-domain subunits are packed in a square planar arrangement to form the pneumolysin oligomer.


Normal uricemia in Lesch-Nyhan syndrome and the association with pulmonary embolism in a young child-a case report and literature review.
Deficiency of hypoxanthine phosphoribosyltransferase activity is a rare inborn error of purine metabolism with subsequent uric acid overproduction and neurologic presentations. The diagnosis of Lesch-Nyhan syndrome (LNS) is frequently delayed until self-mutilation becomes evident. We report the case of a boy aged 1 year and 10 months who was diagnosed with profound global developmental delay, persistent chorea, and compulsive self-mutilation since the age of 1 year. Serial serum uric acid levels showed normal uric acid level, and the spot urine uric acid/creatinine ratio was >2. The hypoxanthine phosphoribosyltransferase cDNA showed the deletion of exon 6, and the boy was subsequently diagnosed to have LNS. He also had respiratory distress due to pulmonary embolism documented by chest computed tomography scan. This report highlights the need to determine the uric acid/creatinine ratio caused by increased renal clearance in LNS in young children. The presence of pulmonary embolism is unusual and may be the consequence of prolonged immobilization.


A voltage-gated pore for translocation of tRNA.
Very little is known about how nucleic acids are translocated across membranes. The multi-subunit RNA Import Complex (RIC) from mitochondria of the kinetoplastid protozoon Leishmania tropica induces translocation of tRNAs across artificial or natural membranes, but the nature of the translocation pore remains unknown. We show that subunits RIC6 and RIC9 assemble on the membrane in presence of subunit RIC4A to form complex R3. Atomic Force Microscopy of R3 revealed particles with an asymmetric surface groove of ∼20 nm rim diameter and ∼1 nm depth. R3 induced translocation of tRNA into liposomes when the pH of the medium was lowered to ∼6 in the absence of ATP. R3-mediated tRNA translocation could also be induced at neutral pH by a K(+) diffusion potential with an optimum of 60-70 mV. Point mutations in the Cys2-His2 Fe-binding motif of RIC6, which is homologous to the respiratory Complex III Fe-S protein, abrogated import induced by low pH but not by K(+) diffusion potential. These results indicate that the R3 complex forms a pore that is gated by a proton-generated membrane potential and that the Fe-S binding region of RIC6 has a role in proton translocation. The tRNA import complex of L. tropica thus contains a novel macromolecular channel distinct from the mitochondrial protein import pore that is apparently involved in tRNA import in some species.


Development of organoid-based drug metabolism model.
Cytochrome P450 (CYP) gene superfamily catalyzes oxidative metabolism of a wide variety of drugs, carcinogens, and endogenous biomolecules in the liver and intestinal organs. In vitro assay platforms such as primary hepatocyte and immortalized liver-derived cell lines have been developed to evaluate drug effects. However, several limitations have been suggested regarding discrepancies between in vitro and in vivo assays. In this study, we aimed to investigate drug metabolism and toxicity based on mouse small intestinal and liver organoids derived from resident stem cells. At first, expressions and activities of CYP subfamilies (CYPs) in intestinal and liver organoids were investigated. Organoids treated with three CYPs-inducers dexamethasone (Dex), β-naphthoflavone (BNF), and 1,4-bis-2-(3, 5-dichloropyridyloxy)-benzene (TCPOBOP) were evaluated for CYPs activities. The CYPs-induced intestinal and liver organoids were confirmed to digest more docetaxel, as colon cancer cell-line survived more in CYPs-induced organoid's medium than in non-induced organoid's medium. Then, the activity of docetaxel in a co-culture platform of mouse liver organoids and human pancreatic tumoroids was measured. We obtained significant statistical values on CYPs-induced metabolic activities: cell survival rates of pancreatic tumoroids co-cultured with docetaxel-treated undifferentiated, differentiated, and CYPs-induced differentiated organoids were 66.05 ± 2.14%, 89.20 ± 2.67%, and 101.90 ± 0.94%, respectively. To sum up, gene expression modification and drug metabolism evaluation were able to be done with organoids as done with tissues. In vivo-like in vitro investigation on drug toxicity may potentially be done with organoids as a stepping bridge to the clinical trial.


Competition between an introduced and an indigenous species: the case of Paspalum paspalodes (Michx) Schribner and Aeluropus littoralis (Gouan) in the Camargue (southern France).
Paspalum paspalodes, an introduced grass species, and Aeluropus littoralis, an indigenous species, develop abundantly in seasonally-flooded marshes in the Camargue (Rhône Delta, France). Although they occur together in many multispecies communities, neither species occurs when the other is dominat. The cultivation of cuttings of P. paspalodes and A. littoralis in a replacement series in a combination of five proportions (0/100, 25/75, 50/50, 75/25 and 100/0) and four salinities (0,2 4, and 6 g Cl- · 1-1) gave contrasting results for the two species: (1) strong asymmetrical competition in favour of P. paspalodes at 0 g Cl- · 1-1, (2) no significant effect of salinity on the mean above-ground and underground yields per plant for A. littoralis over the range tested, (3) a major decrease in the mean above-ground and belowground yields per plant for P. paspalodes with increasing salinity, (4) a reversal of the competitive balance between the species with increasing salinity. The cultivation of cuttings at high temperatures in a greenhouse in a combination of the same five proportions at two salinities (0 and 4 g Cl- · 1-1) refuted the hypothesis that the introduced species is better adapted to summer temperatures. Because it is not salt-tolerant, P. paspalodes cannot be considered as a potentially invasive species in the Camargue. Its abundance depends on newly created and artificially maintained habitats.


Buffering noise: KAT2A modular contributions to stabilization of transcription and cell identity in cancer and development.
KAT2A is a histone acetyltransferase recently identified as a vulnerability in at least some forms of Acute Myeloid Leukemia (AML). Its loss or inhibition prompts leukemia stem cells out of self-renewal and into differentiation with ultimate exhaustion of the leukemia pool. We have recently linked the Kat2a requirement in AML to control of transcriptional noise, reflecting an evolutionary-conserved role of Kat2a in promoting burst-like promoter activity and stabilizing gene expression. We suggest that through this role, Kat2a contributes to preservation of cell identity. KAT2A exerts its acetyltransferase activity in the context of two macromolecular complexes, Spt-Ada-Gcn5-Acetyltransferase (SAGA) and Ada-Two-A-Containing (ATAC), but the specific contribution of each complex to stabilization of gene expression is currently unknown. By reviewing specific gene targets and requirements of the two complexes in cancer and development, we suggest that SAGA regulates lineage-specific programs, and ATAC maintains biosynthetic activity through control of ribosomal protein and translation-associated genes, on which cells may be differentially dependent. While our data suggest that KAT2A-mediated regulation of transcriptional noise in AML may be exerted through ATAC, we discuss potential caveats and probe general vs. complex-specific contributions of KAT2A to transcriptional stability, with implications for control and perturbation of cell identity.


[Patient care and ethics. VIII. Ethics education in dental education in the United States].
Dental ethics with its specific aspects has obtained a distinct profile during the past ten years. This article presents a recent impression of courses in dental ethics at a number of dental schools in the USA. Some reflections are given about the continuing development of dental ethics.


Effects of simulated feeding by snow geese on Scirpus americanus rhizomes.
We simulated the feeding of Greater Snow Geese (Chen caerulescens atlantica) on the rhizomes of three-square bulrush (Scirpus americanus) in a tidal marsh along the St. Lawrence River estuary in Québec. During the spring staging period, aboveground biomass is unavailable and geese feed solely on rhizomes and overwintering buds. An experiment was designed to test the effect of three factors on subsequent growth of Scirpus: the intensity of removal (3 to 77% removal of belowground biomass), the number of "bites" (1, 2 or 3 sections removed) and the number of adventitious buds removed (1, 2 or 3). Rhizomes were dug out in May, treated and transplanted into 85-1 basins sunk in the marsh and filled with marsh soil freed of all plant material. Growth was observed weekly until the end of the growing season in August. Shoots and rhizomes were then collected, dried and weighed to obtain biomass estimates. The net above- and belowground production of Scirpus was inversely related to the initial rhizome biomass removed. At a high level of removal (>35%), the cumulative number of shoots was significantly reduced as early as two weeks after transplantation. The relative reduction in production of the treated rhizomes compared to the control plants was also related to the intensity of removal. An increased number of bites reduced production and the removal of an increased number of adventitious buds further amplified the effect of removal on rhizome production. These experimental results show that even low intensity of feeding by Snow Geese can reduce the production of Scirpus marshes.


Peripheral tissue metabolism during off-pump versus on-pump coronary artery bypass graft surgery: the microdialysis study.
The aim of this study was to monitor and compare metabolic changes in the skeletal muscle during coronary artery bypass grafting surgery with and without cardiopulmonary bypass (CPB) by means of interstitial microdialysis. Glucose, lactate, pyruvate and glycerol were assessed as markers of basic metabolism and tissue perfusion. Twenty patients undergoing surgical myocardial revascularization were enrolled in this pilot study. Ten patients were operated on without CPB (group A, off-pump) and 10 patients using normothermic CPB (group B, on-pump). Interstitial microdialysis was performed by a CMA 60 (CMA/Microdialysis AB, Sweden) probe, inserted into the patient's left deltoid muscle. Microdialysis measurements were performed at 30 min intervals. Glucose, lactate, pyruvate and glycerol were measured in samples using a CMA 600 Analyser (CMA/Microdialysis AB, Sweden). Results in both groups were statistically processed and the groups were compared. Both groups were similar with regards to preoperative characteristics. Dynamic changes of interstitial concentrations of the measured analytes were found in off-pump (group A) and on-pump (group B) patients during the operation. There were no significant differences in dialysate concentrations of glucose and lactate between the groups. Significant differences were detected in pyruvate concentrations, lactate-pyruvate ratio and glycerol concentrations between off-pump versus on-pump patients. Pyruvate concentrations were higher in the off-pump group (p<0.05), the lactate-pyruvate ratios indicating the aerobic/anaerobic metabolism status were lower in the off-pump group (p<0.01) and the values of the concentrations of glycerol were lower in the off-pump group (p<0.01). Dynamic changes in the interstitial concentrations of the glucose, glycerol, pyruvate and lactate were found in both groups of patients (off-pump and on-pump). The presented preliminary results suggest that extracorporeal circulation during cardiac operations could compromise skeletal muscle energy metabolism.


MCPH1/BRIT1 represses transcription of the human telomerase reverse transcriptase gene.
MCPH1, a repressor of human telomerase reverse transcriptase (hTERT) function, is implicated in cellular immortalization. But little is known about how MCPH1 represses telomerase activity. In this study, to determine the mechanism by which MCPH1 regulates hTERT gene expression, we examined the role of MCPH1 in regulating the hTERT promoter in vitro. Co-transfection of the hTERT promoter with MCPH1 in Hela cells could inhibit the hTERT promoter activity. The EMSA assay demonstrated that MCPH1 could bind to the proximal hTERT promoter. Overexpression of MCPH1 could repress telomerase activity, and the repression was abolished by knocking down the MCPH1 expression using siRNA in U2OS cells. We propose that MCPH1 functions as a transcriptional repressor of hTERT in vitro. Since the activation of telomerase, widely observed in human tumor cell lines, is a critical step in tumorigenesis, our findings provide new insights into delineating the tumor-suppressing function of MCPH1 through its down-regulation of hTERT/telomerase expression.


A green spectrophotometric method for the simultaneous determination of nasal binary mixture used in respiratory diseases: Applying isosbestic point and chemometric approaches as a resolving tool, greenness evaluation.
Nasal drug combination is a very useful therapy for elevating the symptoms of various respiratory diseases as seasonal allergic rhinitis and infectious respiratory illness as pandemic COVID-19. One of best combination is Fluticasone propionate (FLU) and Azelastine (AZE). In this study, different UV spectrophotometric and chemometric methods have been applied for quantitative analysis of FLU and AZE without previous separation in their pure form, laboratory prepared mixture and pharmaceutical dosage form. Absorbance subtraction (AS) and Amplitude modulation (AM) spectrophotometric methods have been applied for the simultaneous determination of the cited drugs. Besides, three well-known chemometric techniques; namely, classical least squares (CLS), partial least square (PLS), and principal component regression (PCR) have been applied for the simultaneous analysis of both drugs by using spectrophotometric data. To be friendly to the environment, the greenness of the proposed methods was taken into consideration and evaluation of the analytical methods' greenness was done using two green analytical chemistry metrics known as, Analytical Greenness Calculator and an eco-scale scoring method. They indicated that the methods were environmentally friendly in relation to numerous approaches like instrument, reagents, and safety of waste. Analyzing laboratory prepared mixtures including different quantities of FLU and AZE, as well as their marketed dose form, was used to assess the selectivity of the applied methods. The validity of the developed methods was investigated by applying the standard addition technique. The resulting data were statistically compared to those obtained by the official or reported HPLC methods for FLU and AZE, which revealed no significant difference in accuracy and precision at p = 0.05.


Studies of the glycine cleavage enzyme system in brain from infants with glycine encephalopathy.
Glycine content and enzyme activity of the glycine cleavage system were compared in autopsied brain from five infants dying with glycine encephalopathy and four control infants, including two with other types of hyperglycinemia. Glycine content was elevated 2- to 8-fold and glycine cleavage enzyme activity was undetectable in the brains of the glycine encephalopathy patients. Glycine content and enzyme activity were normal in the brains of the control patients, including one with ketotic hyperglycinemia secondary to methylmalonic acidemia. Prolonged dialysis failed to restore glycine cleavage enzyme activity in brain homogenates of glycine encephalopathy patients, and these homogenates failed to inhibit enzyme activity when added to homogenates of control brain. Radioactive bicarbonate was converted to radioactive glycine by control brain, but not by glycine encephalopathy brain. This finding, together with the results of recombination experiments between solubilized human brain enzymes and purified protein components of the bacterial glycine cleavage system of Arthrobacter globiformis, indicates that the enzyme defect in glycine encephalopathy involves at least the second or H protein of the 4-protein glycine cleavage enzyme system.


Aneurysmal malformation of the vein of Galen in three patients: clinical and radiological follow-up.
We studied three patients with aneurysmal malformations of the vein of Galen: all underwent embolisation followed by MRI and conventional angiography; two also underwent postembolisation magnetic resonance angiography (MRA). MRI was performed before treatment in two patients, MRA in only one, diagnosed prenatally. Two patients had normal appearances on follow-up MR studies and were completely cured by embolisation. However, the last patient, after two embolisations, despite the stabilisation of the clinical condition, underwent surgery and died. We think MRI is mandatory before endoarterial treatment, to assess the conditions of the brain. Angiography is mandatory only at the time of endovascular treatment, while MRA and MRI have a role in follow-up. Endoarterial embolisation remains the treatment of choice, and surgery is not advisable.


[Vitamin D-metabolism and rickets (author's transl)].
By new methods Vitamin D metabolites can now be determined in small quantities of biological fluids. These methods have revealed further details about Vitamin D metabolism as well as the pathogeneses and therapy of the various types of rickets. A review of this topic will be presented.


Separation mechanism of nortriptyline and amytriptyline in RPLC.
The single and the competitive equilibrium isotherms of nortriptyline and amytriptyline were acquired by frontal analysis (FA) on the C18- bonded discovery column, using a 28/72 (v/v) mixture of acetonitrile and water buffered with phosphate (20 mM, pH 2.70). The adsorption energy distributions (AED) of each compound were calculated from the raw adsorption data. Both the fitting of the adsorption data using multi-linear regression analysis and the AEDs are consistent with a trimodal isotherm model. The single-component isotherm data fit well to the tri-Langmuir isotherm model. The extension to a competitive two-component tri-Langmuir isotherm model based on the best parameters of the single-component isotherms does not account well for the breakthrough curves nor for the overloaded band profiles measured for mixtures of nortriptyline and amytriptyline. However, it was possible to derive adjusted parameters of a competitive tri-Langmuir model based on the fitting of the adsorption data obtained for these mixtures. A very good agreement was then found between the calculated and the experimental overloaded band profiles of all the mixtures injected.


Assessing cancer-related distress in cancer patients and caregivers receiving outpatient psycho-oncological counseling.
The diagnosis of cancer, the symptoms of the illness and its treatment have an influence on how patients and their caregivers experience distress. However, data focusing on caregivers and their cancer-related distress in the outpatient setting is sparse. This study aimed to compare cancer-related distress of caregivers and patients and to derive implications for the system of outpatient psycho-oncological care. One hundred thirty-eight patients and 102 caregivers receiving psycho-oncological counseling completed a standardized interview based on a self-assessment questionnaire (Questionnaire on Stress in Cancer Patients, FBK). Group comparisons for cancer-related distress revealed one statistically significant difference for the subscale 'Fear' of the FBK, Z = 2.308, p = .021, and d = .44. Caregivers showed higher cancer-related fear (M = 2.76, SD = 1.14) than patients (M = 2.41, SD = 1.29). There were no differences in 'psychosomatic complaints', 'information deficit', 'restrictions in everyday life', 'social strains', or the total score of the FBK. Caregivers seem to experience cancer-related distress equal to or even more severely than patients themselves. Results suggest that there is a need for more low-threshold offers of outpatient psycho-oncological counseling for caregivers.


Effect of emotional valence on retrieval-related recapitulation of encoding activity in the ventral visual stream.
While prior work has shown greater retrieval-related reactivation in the ventral visual stream for emotional stimuli compared to neutral stimuli, the effects of valence on retrieval-related recapitulation of successful encoding processes (Dm effects) have yet to be investigated. Here, seventeen participants (aged 19-35) studied line drawings of negative, positive, or neutral images followed immediately by the complete photo. After a 20-min delay, participants performed a challenging recognition memory test, distinguishing the studied line drawing outlines from novel ones. First, results replicated earlier work by demonstrating that negative and positive hits elicited greater ventral occipito-temporal cortex (VOTC) activity than neutral hits during both encoding and retrieval. Moreover, the amount of activation in portions of the VOTC correlated with the magnitude of participants' emotional memory enhancement. Second, results revealed significant retrieval-related recapitulation of Dm effects (Hits>Misses) in VOTC (anterior inferior temporal gyri) only for negative stimuli. Third, connectivity between the amygdala and fusiform gyrus during the encoding of negative stimuli increased the likelihood of fusiform activation during successful retrieval. Together, these results suggest that recapitulation in posterior VOTC reflects memory for the affective dimension of the stimuli (Emotional Hits>Neutral Hits) and the magnitude of activation in some of these regions is related to superior emotional memory. Moreover, for negative stimuli, recapitulation in more anterior portions of the VOTC is greater for remembered than forgotten items. The current study offers new evidence for effects of emotion on recapitulation of activity and functional connectivity in support of memory.


Interactions of polymerizable phosphatidylcholine vesicles with blood components: relevance to biocompatibility.
We have studied the biocompatibility properties of polymerizable phosphatidylcholine bilayer membranes, in the form of liposomes, with a view toward the eventual utilization of such polymerized lipid assemblies in drug carrier systems or as surface coatings for biomaterials. The SH-based polymerizable lipid 1,2-bis[1,2-(lipoyl)dodecanoyl]-sn-glycero-3-phosphocholine (dilipoyl lipid, DLL) and the methacryl-based lipid 1,2-bis[(methacryloyloxy)dodecanoyl]-sn-glycero-3-phosphocholine (dipolymerizable lipid, DPL) were studied in comparison to 'conventional' zwitterionic or charged phospholipids. We examined binding of serum proteins to liposomes and effects of liposomes on fibrin clot formation and on platelet aggregation. All types of liposomes tested bound complex mixtures of serum proteins with IgG being the most abundant bound component. DPL vesicles and anionic vesicles bound substantially more protein than other vesicle types. Polymerized DPL vesicles uniquely bound a protein of about 53 kDa which was not bound to other types of phosphatidylcholine liposomes. Likewise polymerized DPL vesicles, but not other types of phosphatidylcholine vesicles, caused a marked alteration in coagulation as measured by activated partial thromboplastin time (APTT) and prothrombin time (PT) tests; this effect was shown to be due to binding and depletion of clothing factor V by the DPL polymerized vesicles. Polymerized DPL liposomes and DLL liposomes in polymerized or nonpolymerized form, were without substantial effect on platelet aggregation. However, DPL nonpolymerized vesicles, while not causing aggregation, did impair ADP-induced aggregation of platelets. These studies suggest that SH based polymerizable lipids of the DLL type may be very suitable for in vivo use in the contexts of drug delivery systems or biomaterials development. Methacryloyl-based lipids of the DPL type seem to display interactions with the hemostatic process which militate against their in vivo utilization.


Same-Day versus Next-Day Dexamethasone Intracanalicular Insert Administration for Inflammation and Pain Control Following Cataract Surgery: A Retrospective Analysis.
The dexamethasone 0.4mg intracanalicular insert (Dextenza, Ocular Therapeutix, Bedford, MA) is approved for control of postoperative pain and inflammation following ocular surgery. This study compared pain and inflammation resolution following phacoemulsification in eyes that received the insert immediately postoperatively versus the next day. This was a retrospective analysis of existing electronic health records. Consecutive qualifying eyes were included for analysis. All patients received perioperative antibiotics and nonsteroidal anti-inflammatory drugs. Pain and inflammation were assessed at baseline and on postoperative days 1, 7, and 30. Pain was assessed by dichotomous patient report (present/absent). Anterior chamber cell (0, 0.5+, 1-4+) and flare (0-4+) were graded using the Standardization of Uveitis Nomenclature rubric. Data from 17 eyes of 17 subjects were analyzed; 8 received the insert immediately postoperative and 9 in the office the next day. In both groups, trace cell was present in all eyes at day 1 and had resolved in all but 1 eye in each group at days 7 and 30. Flare was absent in all eyes at every time point, and transient pain was reported in a single same-day eye on day 7. No insert-related adverse events were observed, and no eyes required rescue corticosteroid therapy or insert removal. Similar rates of inflammation and pain resolution after phacoemulsification were observed with the dexamethasone intracanalicular insert placed either immediately postoperatively or the next day.