Evolution of Landscape Ecological Risk at the Optimal Scale: A Case Study of the Open Coastal Wetlands in Jiangsu, China.
Detailed analysis of the evolution characteristics of landscape ecological risk is crucial for coastal sustainable management and for understanding the potential environmental impacts of a man-made landform landscapes (MMLL). As a typical open coastal wetland, large-scale human activities (e.g., tidal reclamation, fishery activities, wind farm construction, and port construction) have substantially affected the evolution of the coastal ecological environment. Previous landscape ecological risk assessment studies have documented the effectiveness of assessing the quality of ecological environment processes. However, these studies have either focused on the noncoastal zone, or they have not considered the evolution of the spatial characteristics and ecological risk evolution of the landscape at an optimal scale. Here, we present a landscape ecological risk pattern (LERP) evolution model, based on two successive steps: first, we constructed an optimal scale method with an appropriate extent and grain using multi⁻temporal Landsat TM/OLI images acquired in the years 2000, 2004, 2008, 2013 and 2017, and then we calculated landscape ecological risk indices. Based on this model, the entire process of the spatiotemporal evolution of ecological risk patterns of the open coastal wetlands in Jiangsu, China, was determined. The principal findings are as follows: (1) The main landscape types in the study area are tidal flats and farmland, and the main features of the landscape evolution are a significant increase in aquafarming and a substantial decrease in the tidal flat area, while the landscape heterogeneity increased; (2) In the past 20 years, the areas of low and relatively low ecological risk in the study region were greatly reduced, while the areas of medium, relatively high, and high ecological risk greatly increased; the areas of high-grade ecological risk areas are mainly around Dongtai and Dafeng; (3) The area of ecological risk from low-grade to high-grade occupied 71.75% of the study area during 2000⁻2017. During the previous periods (2000⁻2004 and 2004⁻2008), the areas of low-grade ecological risk were transformed to areas of middle-grade ecological risk area, while during the later periods (2008⁻2013 and 2013⁻2017) there was a substantial increase in the proportion of areas of high-grade ecological risk. Our results complement the official database of coastal landscape planning, and provide important information for assessing the potential effects of MMLL processes on coastal environments.


Spatiotemporal dynamics of autophagy receptors in selective mitophagy.
Damaged mitochondria are turned over through a process of selective autophagy termed mitophagy. In mitophagy, unhealthy mitochondria are recognized and ubiquitinated by Parkinson disease-linked proteins PINK1 and PARK2. The subsequent recruitment of ubiquitin-binding autophagy receptors leads in turn to the sequestration of the damaged organelles into LC3-positive phagophores, precursors to autophagosomes. The precise identity of these receptors and how they are regulated has been the focus of considerable attention. Our recent work uses live-cell imaging to explore the dynamics and regulation of autophagy receptor recruitment. Utilizing multiple paradigms to induce mitochondrial damage, we identified the rapid, 2-step recruitment of autophagy receptors OPTN, CALCOCO2/NDP52, and TAX1BP1. All 3 receptors are recruited to damaged mitochondria with similar kinetics; however, only OPTN is necessary for efficient formation of a phagophore sequestering damaged mitochondria from the cytosol. OPTN is co-recruited to damaged mitochondria along with its upstream kinase TBK1. Depletion of OPTN or TBK1, or expression of amyotrophic lateral sclerosis (ALS)-linked mutations in either protein, interfere with efficient autophagic engulfment of depolarized mitochondria. These observations suggest that insufficient autophagy of damaged mitochondria may contribute to neurodegenerative disease.


[Gennai Hiraga and Bosho: with special reference to the manuscripts kept by the Suzukis, Izu].
Bosho is one of the important mineral drugs in the Edo era. Gennai Hiraga (1728-1779) gave a lot of space to the item of natural product Bokusho in his book "Butsurui-hinshitsu" (1763). Gennai made bosho from bokusho that was deposited at spring in Kamifunabara is little known to us except "Butsurui-hinshitsu". In Kamifunabara, we got an opportunity to survey the manuscripts kept by the Suzukis, which show Gennai's visit and activities there. The object of this paper is to introduce the manuscripts kept by the Suzukis and also to consider widely the knowledge of Gennai and his teacher Ransui Tamura (1718-1776) concerning bosho and related materials.


Outcomes after ascending aorta and proximal aortic arch repair using deep hypothermic circulatory arrest with retrograde cerebral perfusion: analysis of 207 patients.
Correction of ascending aorta and proximal aortic arch pathology with numerous surgical techniques having been proposed over the years remains a surgical challenge. This study was undertaken to identify risk factors influencing outcome after aortic arch operations, requiring deep hypothermic circulatory arrest (DHCA). Between 1993 and 2010, 207 consecutive patients were operated for ascending aorta and proximal arch correction with the use of deep hypothermic circulatory arrest with retrograde cerebral perfusion. All patients were followed up with regular out-patient clinics, transthoracic echocardiography and, when required, chest computed tomography. There were 102 (49.3%) emergencies (acute type A dissection) and 105 (50.7%) elective cases. Mean age: 63.5 ± 12 years. Mean circulatory arrest time was 25.4 ± 13 min. Unadjusted analysis of factors associated with 30-day mortality revealed emergency status, preoperative hemodynamic instability, acute dissection, reoperation, increased circulatory arrest time, postoperative bleeding, postoperative creatinine levels and presence of neurological dysfunction. Multi-adjusted analysis revealed duration of circulatory arrest as the only and main factor related to death. Thirty-day mortality was 2.4% for the elective and 7.2% for emergencies cases. Survival during long-term follow-up was 93, 82 and 53% at 1, 5 and 10 years, respectively. Ascending aorta and proximal aortic arch replacement with brief duration of deep hypothermic circulatory arrest combined with retrograde cerebral perfusion is a safe method with acceptable short- and long-tem results.


Nanofibrous Membrane Promotes and Sustains Vascular Endothelial Barrier Function.
The vascular endothelium serves as a physical barrier between the circulating blood and surrounding tissue and acts as a critical regulator of various physiological processes. In vitro models involving vasculature rely on the maintenance of the endothelial barrier function. In this study, we fabricated 2D aligned nanofibrous membranes with distinct pore sizes via electrospinning and investigated the effect of membrane pore size on endothelial barrier function. Our results demonstrated that the use of the nanofibrous membranes promoted the formation of a tight vascular endothelium and sustained barrier function for over one month in comparison with conventional transwell setups. Moreover, the examination of the nucleocytoplasmic localization of yes-associated protein (YAP) in the endothelial cells indicated that nanofibrous membrane promoted YAP expression and its nuclear localization, critical to endothelial barrier function. Furthermore, the comparison of permeability between random and aligned nanofibrous membranes underscored the importance of pore size in preserving barrier function. Our findings offer a valuable strategy for creating more physiologically relevant in vitro vascular models and contribute to the understanding of endothelial barrier formation and maintenance mechanisms.


Interactions of the amphiphiles arbutin and tryptophan with phosphatidylcholine and phosphatidylethanolamine bilayers in the dry state.
Water is essential for life, but some organisms can survive complete desiccation, while many more survive partial dehydration during drying or freezing. The function of some protective molecules, such as sugars, has been extensively studied, but much less is known about the effects of amphiphiles such as flavonoids and other aromatic compounds. Amphiphiles may be largely soluble under fully hydrated conditions, but will partition into membranes upon removal of water. Little is known about the effects of amphiphiles on membrane stability and how amphiphile structure and function are related. Here, we have used two of the most intensively studied amphiphiles, tryptophan (Trp) and arbutin (Arb), along with their isolated hydrophilic moieties glycine (Gly) and glucose (Glc) to better understand structure-function relationships in amphiphile-membrane interactions in the dry state. Fourier-transform infrared (FTIR) spectroscopy was used to measure gel-to-liquid crystalline phase transition temperatures (Tm) of liposomes formed from phosphatidylcholine and phosphatidylethanolamine in the presence of the different additives. In anhydrous samples, both Glc and Arb strongly depressed Tm, independent of lipid composition, while Gly had no measurable effect. Trp, on the other hand, either depressed or increased Tm, depending on lipid composition. We found no evidence for strong interactions of any of the compounds with the lipid carbonyl or choline groups, while all additives except Gly seemed to interact with the phosphate groups. In the case of Arb and Glc, this also had a strong effect on the sugar OH vibrations in the FTIR spectra. In addition, vibrations from the hydrophobic indole and phenol moieties of Trp and Arb, respectively, provided evidence for interactions with the lipid bilayers. The two amphiphiles Arb and Trp interact differently with dry bilayers. The interactions of Arb are dominated by contributions of the Glc moiety, while the indole governs the effects of Trp. In addition, only Trp-membrane interactions showed a strong influence of lipid composition. Further investigations, using the large structural diversity of plant amphiphiles will help to understand how their structure determines the interaction with membranes and how that influences their biological functions, for example under freezing or dehydration conditions.


Double enzyme-catalyzed microreactors using capillary electrophoresis.
This work evaluates the concept of a double enzyme-catalyzed microreactor using capillary electrophoresis (CE). Migrating in a capillary under electrophoresis conditions, plugs of substrate and two enzymes are injected separately in buffer and allowed to react. Extent of reaction and product ratios were subsequently determined by CE. This concept is demonstrated using two model systems: the conversion of adenosine triphosphate (ATP) to adenosine diphosphate (ADP) and adenosine monophosphate (AMP) by hexokinase (HK, EC 18.104.22.168) and apyrase (APY, EC 18.104.22.168), respectively, in the conversion of glucose to glucose-6-phosphate and inorganic phosphate, respectively, and the conversion of nicotinamide adenine dinucleotide, reduced form (NADH), to nicotinamide adenine dinucleotide (NAD) and back to NADH by lactate dehydrogenase (LDH, EC 220.127.116.11) and glucose-6-phosphate dehydrogenase (G6PDH, EC 22.214.171.124), respectively, in the conversion of pyruvate to lactate and glucose-6-phosphate (glc-6-P) to 6-phosphogluconate, respectively. These procedures illustrate the use of the capillary as a double microreactor and the ease of quantitation of reaction products under conditions of electrophoresis.


Dental anomalies in familial adenomatous polyposis coli.
Forty-seven Danish and 50 Finnish patients with familial adenomatous polyposis coli (FPC) were studied by panoramic tomography (PTG) of the mandible, which showed dental abnormalities in 17% of the cases. Eleven patients (11%) had supernumerary teeth and/or compound osteomas, and nine patients (9%) had impacted permanent teeth. The frequency of the dental anomalies was statistically significantly higher in FPC patients than in the normal population; it is therefore concluded that this dental abnormality should be included in the list of extracolonic manifestations that may occur in any FPC patient. The frequency of dental anomalies was higher in Finnish than in Danish patients, probably owing to a higher frequency of extracolonic manifestations in the Finnish series.


Cip29 is phosphorylated following activation of the DNA damage response in Xenopus egg extracts.
Acting through a complex signalling network, DNA lesions trigger a range of cellular responses including DNA repair, cell cycle arrest, altered gene expression and cell death, which help to limit the mutagenic effects of such DNA damage. RNA processing factors are increasingly being recognised as important targets of DNA damage signalling, with roles in the regulation of gene expression and also more directly in the promotion of DNA repair. In this study, we have used a Xenopus laevis egg extract system to analyse the DNA damage-dependent phosphorylation of a putative RNA export factor, Cip29. We have found that Cip29 is rapidly phosphorylated in response to DNA double-strand breaks in this experimental system. We show that the DNA damage-inducible modification of Cip29 is dependent on the activity of the key double-strand break response kinase, ATM, and we have identified a conserved serine residue as a damage-dependent phosphorylation site. Finally, we have determined that Cip29 is not required for efficient DNA end-joining in egg extracts. Taken together, these data identify Cip29 as a novel target of the DNA damage response and suggest that the damage-dependent modification of Cip29 may relate to a role in the regulation of gene expression after DNA damage.


Small Molecule Enhancement of 20S Proteasome Activity Targets Intrinsically Disordered Proteins.
The 20S proteasome is the main protease for the degradation of oxidatively damaged and intrinsically disordered proteins. When accumulation of disordered or oxidatively damaged proteins exceeds proper clearance in neurons, imbalanced pathway signaling or aggregation occurs, which have been implicated in the pathogenesis of several neurological disorders. Screening of the NIH Clinical Collection and Prestwick libraries identified the neuroleptic agent chlorpromazine as a lead agent capable of enhancing 20S proteasome activity. Chemical manipulation of chlorpromazine abrogated its D2R receptor binding affinity while retaining its ability to enhance 20S mediated proteolysis at low micromolar concentrations. The resulting small molecule enhancers of 20S proteasome activity induced the degradation of intrinsically disordered proteins, α-synuclein, and tau but not structured proteins. These small molecule 20S agonists can serve as leads to explore the therapeutic potential of 20S activation or as new tools to provide insight into the yet unclear mechanics of 20S-gate regulation.


Surface Adsorption of Suwannee River Humic Acid on TiO2 Nanoparticles: A Study of pH and Particle Size.
TiO2 nanoparticles are some of the most widely used metal oxide nanomaterials mainly because of their diverse industrial applications. Increasing usage of these nanoparticles raises concerns about the potential adverse effects on the environment. Humic acid is a ubiquitous component of the natural organic matter in the environment that is known to get adsorbed onto nanoparticle surfaces. In this study, adsorption of humic acid on TiO2 nanoparticles of two different sizes (5 and 22 nm) is studied at different environmentally relevant pH values using attenuated total reflectance Fourier transformation infrared spectroscopy. These vibrational spectra provide insights into the nature of the adsorption process (extent of adsorption and reversibility) as a function of pH as well as information about the bonding to the surface. Additionally, the impact of humic acid adsorption on surface charge and agglomeration has been investigated. Interestingly, the results show that the humic acid adsorption is strongly pH-dependent and that adsorption of humic acid on TiO2 nanoparticles alters the extent of agglomeration and modifies the zeta potential and surface charges depending on the pH, thus potentially increasing the bioavailability of TiO2 nanoparticles in the environment.


Patients' Hand Washing and Reducing Hospital-Acquired Infection.
Hand hygiene is important to prevent hospital-acquired infections. Patients' hand hygiene is just as important as hospital workers' hand hygiene. Hospital-acquired infection rates remain a concern across health centers. To improve patients' hand hygiene through the promotion and use of hand washing with soap and water, hand sanitizer, or both and improve patients' education to reduce hospital-acquired infections. In August 2013, patients in a cardiothoracic postsurgical step-down unit were provided with individual bottles of hand sanitizer. Nurses and nursing technicians provided hand hygiene education to each patient. Patients completed a 6-question survey before the intervention, at hospital discharge and 1, 2, and 3 months after the intervention. Hospital-acquired infection data were tracked monthly by infection prevention staff. Significant correlations were found between hand hygiene and rates of infection with vancomycin-resistant enterococci (P = .003) and methicillin-resistant Staphylococcus aureus (P = .01) after the intervention. After the implementation of hand hygiene interventions, rates of both infections declined significantly and patients reported more staff offering opportunities for and encouraging hand hygiene. This quality improvement project demonstrates that increased hand hygiene compliance by patients can influence infection rates in an adult cardiothoracic step-down unit. The decreased infection rates and increased compliance with hand hygiene among the patients may be attributed to the implementation of patient education and the increased accessibility and use of hand sanitizer.


Childhood epilepsy syndromes with both focal and generalized seizures.
Childhood is a time of considerable importance for the onset of epilepsy syndromes. Selection of an appropriate antiepileptic drug (AED) is central to its successful management. Different AEDs have various effects depending on whether seizures are focal or generalized and this is often used as a rational basis for drug selection. Syndromes, in which features of both focal and generalized seizures are associated in a single patient, present particular problems for pediatric prescribing and epilepsy management since an AED suitable for one seizure type may be ineffective for, or even aggravate, another seizure type. This review discusses the syndromes with different seizures types, focal and generalized, examines the treatment options that may be useful in each case and highlights the potential of some of the newer AEDs in managing these difficult syndromes.


Effectiveness of a community health worker as sole diabetes educator: comparison of CoDE with similar culturally appropriate interventions.
The feasibility of a newly designed Community Diabetes Education (CoDE) intervention was evaluated in preparation for the development of a pilot study of this program. A comparison between CoDE and similar culturally appropriate diabetes management programs developed specifically for Hispanic Americans demonstrates its unique features. Patient insurance status, duration of the intervention, delivery in individual and/or group settings, the characteristics of the diabetes educator(s), the other professional resources involved in these interventions, the associated costs, and the reported health outcomes were used in the comparison. The significant improvement in hemoglobin A1c observed in patients who completed one year of CoDE suggests that a community health worker can serve as the primary patient educator in the absence of more highly educated personnel required by American Diabetes Association-certified diabetes education programs. This low-cost model can be reproduced de novo in community health centers or inserted into existing diabetes management interventions.


Effect of soda ash industry effluent on agarophytes, alginophytes and carrageenophyte of west coast of India.
This paper presents the results of a study on the impact of the effluent released by the soda ash industry on important red and brown macro algal species Gelidiella acerosa, Gracilaria corticata, Soleria robusta, Sargassum tenerrimum, Padina tetrastromatica in the tidal zone around Veraval, on the west coast of India, in the lowest low water tide of December 2003. The study examined the effect of effluent discharge on availability of biomass and percentage of phyco-colloids extraction such as agar, alginic acid and carrageen of these commercial seaweeds.


Major Depression Comorbid with Medical Conditions: Analysis of Quality of Life, Functioning, and Depressive Symptom Severity.
The presence of Major Depressive Disorder (MDD) is often comorbid in patients with a variety of general medical conditions (GMCs) which could lead to less favorable outcomes. The goal of this analysis is to examine functional outcomes of QOL and functioning before and after antidepressant treatment among patients with MDD with and without GMCs. We performed a secondary analysis based on the STAR*D database. The analysis included two patient groups from the STAR*D trial: 1,198 patients comorbid with MDD and GMCs (MDD + GMC) and 1,082 patients with MDD and no GMCs (MDDnoGMC), as defined by the Cumulative Illness Rating Scale. We analyzed depressive symptom severity, functioning and quality of life (QOL) before and after level 1 treatment with citalopram. At baseline, the MDD + GMC group had significantly lower QOL (p < 0.001) and functioning (p = 0.001) than the MDDnoGMC group, although depressive symptom severity was not significantly different. Following antidepressant treatment, QOL, functioning and depressive symptom severity significantly improved for both MDD + GMC and MDDnoGMC groups. However, patients with MDD + GMC were more likely to experience severe impairments in QOL in (56.8% vs. 43.5% for MDDnoGMC, p < 0.001) and functioning (42.5% vs. 29.3% for MDDnoGMC, p < 0.001) following treatment. The remission rate was significantly lower for MDD + GMC (30.6% vs. 41.1% for MDDnoGMC, p < 0.001). Our findings suggest that antidepressant treatment had a positive impact on patients with and without GMCs. However, those with GMCs experienced not only a lower remission rate, but also continued to experience more significantly severe impairments in QOL and functioning.


First Observation of Hemoglobin Pyrgos [ß83(EF7) Gly→Asp] in Turkish Population.
Hemoglobin Pyrgos [ß83 (EF7) Gly→Asp] is a rare hemoglobin variant. This report describes the first observation of this variant in an 18-year-old Turkish girl living in Isparta.


Relationship between cognitive function affecting motor Functional Independence Measure and hypnotics.
Otsubo H, Kishimoto K, Hirano I, Nakano H, Itaya K, Kumaki R, Osumi H. Relationship between cognitive function affecting motor Functional Independence Measure and hypnotics. Jpn J Compr Rehabil Sci 2022; 13: 4-11. The purpose of this study was to examine the relationship between cognitive dysfunction affecting motor Functional Independence Measure (FIM) and hypnotics. This was a retrospective study involving 509 patients aged ≥ 65 years who were discharged from a convalescent rehabilitation ward. Multiple regression analysis was performed with motor FIM efficiency and motor FIM effectiveness (motor FIM-e) as independent variables and the presence or absence of cognitive dysfunction as the dependent variable. The use of hypnotics in patients with cognitive dysfunction showed a positive relationship with motor FIM efficiency (β = 0.147, P = 0.019) and motor FIM-e (β = 0.141, P = 0.026). Multiple regression analyses were performed after further classifying hypnotics by therapeutic class into hypnotics with new mechanisms, non-benzodiazepine (BZ) hypnotics, and BZ hypnotics. Non-BZ hypnotics (β = 0.141, P = 0.021) showed a positive relationship with motor FIM efficiency. Non-BZ hypnotics (β = 0.158, P = 0.009) and BZ hypnotics (β = 0.178, P = 0.003) showed a positive relationship with motor FIM-e, whereas hypnotics with new mechanisms of action did not. In contrast, none of the three combinations of hypnotics showed any significant relationship with either motor FIM efficiency or motor FIM-e in patients without cognitive dysfunction. The results suggested that the use of hypnotics in patients with cognitive dysfunction increases motor FIM efficiency and motor FIM-e.


Causes and effects of the low T3 syndrome during caloric deprivation and non-thyroidal illness: an overview.
The increased serum reverse T3 and decreased T3 during caloric deprivation and non-thyroidal illness is caused by decreased T3 production (with intact degradation) and reversed T3 degradation (with intact production) respectively. These changes can ensue from two mechanisms i.e. decreased 5'D of T4 and of reverse T3 (possibly caused by a decrease in naturally occurring reducing agents) or by decreased transport of T4 and reverse T3 into the liver (possibly caused by decreased ATP concentrations in the liver). The effects of the low T3 syndrome at the tissue level are in many instances comparable to those seen in hypothyroidism. The effects lead to conservation of energy and decrease of protein breakdown. These effects are considered to constitute a beneficial adaptative mechanism in situations in which the organism is endangered. There is no evidence that treatment of patients with the low T3 syndrome with thyroid hormones is of any benefit. Knowledge at the present moment suggests that administration of thyroid hormones during caloric deprivation or non-thyroidal illness should be avoided.


Silver-catalyzed imination of sulfoxides and sulfides.
[reaction: see text] Silver salts in the presence of a chelating ligand efficiently catalyze the stereospecific imination of sulfoxides and sulfides with sulfonylamides and PhI(OAc)(2) to afford sulfoximines and sulfilimines, respectively, in good yields.


(-)-CGP 12177 causes cardiostimulation and binds to cardiac putative beta 4-adrenoceptors in both wild-type and beta 3-adrenoceptor knockout mice.
Some blockers of beta1- and beta2-adrenoceptors cause cardiostimulant effects through an atypical beta-adrenoceptor (putative beta4-adrenoceptor) that resembles the beta3-adrenoceptor. It is likely but not proven that the putative beta4-adrenoceptor is genetically distinct from the beta3-adrenoceptor. We therefore investigated whether or not the cardiac atypical beta-adrenoceptor could mediate agonist effects in mice lacking a functional beta3-adrenoceptor gene (beta3 KO). (-)-CGP 12177, a beta1- and beta2-adrenoceptor blocker that causes agonist effects through both beta3-adrenoceptors and cardiac putative beta4-adrenoceptors, caused cardiostimulant effects that were not different in atria from wild-type (WT) mice and beta3 KO mice. The effects of (-)-CGP 12177 were resistant to blockade by (-)-propranolol (200 nM) but were blocked by (-)-bupranolol (1 microM) with an equilibrium dissociation constant of 15 nM in WT and 17 nM in beta3 KO. (-)-[3H]CGP 12177 labeled a similar density of the putative beta4-adrenoceptor in ventricular membranes from the hearts of both WT (Bmax = 52 fmol/mg protein) and beta3 KO (Bmax = 53 fmol/mg protein) mice. The affinity of (-)-[3H]CGP 12177 for the cardiac putative beta4-adrenoceptor was not different between WT (Kd = 46 nM) and beta3 KO (Kd= 40 nM). These results provide definitive evidence that the cardiac putative beta4-adrenoceptor is distinct from the beta3-adrenoceptor.


Cytokines and chronic fatigue syndrome.
Chronic fatigue syndrome (CFS) patients show evidence of immune activation, as demonstrated by increased numbers of activated T lymphocytes, including cytotoxic T cells, as well as elevated levels of circulating cytokines. Nevertheless, immune cell function of CFS patients is poor, with low natural killer cell cytotoxicity (NKCC), poor lymphocyte response to mitogens in culture, and frequent immunoglobulin deficiencies, most often IgG1 and IgG3. Immune dysfunction in CFS, with predominance of so-called T-helper type 2 and proinflammatory cytokines, can be episodic and associated with either cause or effect of the physiological and psychological function derangement and/or activation of latent viruses or other pathogens. The interplay of these factors can account for the perpetuation of disease with remission/exacerbation cycles. A T-helper type 2 predominance has been seen among Gulf War syndrome patients and this feature may also be present in other related disorders, such as multiple chemical sensitivity. Therapeutic intervention aimed at induction of a more favorable cytokine expression pattern and immune status appears promising.


The Impact of Psychiatric Practice Guidelines on Medication Costs and Youth Aggression in a Juvenile Justice Residential Treatment Program.
Stakeholders have expressed concern over the appropriate use of psychiatric medications and adequacy of mental health services for youths involved with the juvenile justice system. This study assessed the impact of implementing psychiatric practice guidelines on medication costs and youth aggression in a juvenile justice facility. The study examined whether implementing psychiatric practice guidelines in a facility with an organized psychosocial treatment program would reduce psychiatric medication costs, compared with two other facilities, and whether lower psychotropic medication costs would be associated with increases in youth aggression. Administrative data from three state-run juvenile justice facilities were analyzed to determine psychiatric medication costs and rates of youth aggression. Psychiatric practice guidelines that involved screening, shared decision making, psychosocial treatments, medication prescribing, and monitoring of side effects were implemented in only one of the three facilities, with a goal of applying evidence-based psychopharmacology and benefit-risk considerations. Over the ten-year study period (2003-2012), psychiatric medication costs decreased 26% at the facility implementing the psychiatric practice guidelines, whereas costs at the two comparison facilities increased by 104% and 152%. As psychiatric medication costs decreased at the facility implementing the guidelines, youth aggression there did not increase. Implementing psychiatric practice guidelines in juvenile justice facilities can reduce psychotropic medication costs without an increase in youth aggression. Implementation of the guidelines requires an organized psychosocial treatment program to help deter an inappropriate focus on psychotropic treatments.


The Daily Rhythmic Changes of Undergraduate Students' Emotions: An Analysis Based on Tencent Tweets.
Emotional stability is of great importance for undergraduates and has significant predictive power for mental health. Emotions are associated with individuals' daily lives and routines. Undergraduates commonly post their opinions and feelings on social networks, providing a huge amount of data for studying their emotional states and rhythms. Based on the construction of the emotion dictionary of undergraduates' Tencent tweets (TTs)-a social network for users to share their life situations and express emotions and feelings to friends-we used big data text analysis technology to analyze the emotion words in 45,996 Tencent tweets published by 894 undergraduates. Then, we used hierarchical linear modeling to further analyze the daily rhythms of undergraduate students' emotions and how demographic variables are associated with the daily rhythmic changes. The results were as follows: (1) Undergraduates tweeted about more positive emotions than negative emotions (love was most common and fear was the least common); (2) The emotions in undergraduates' tweets changed considerably from 1 a.m. to 6 a.m., but were fairly stable during the day; (3) There was a rising trend in the frequency of using emotion words in Tencent tweets during the day as each hour progressed, and there was a higher increase in positive emotion than negative emotion; and (4) The word frequencies and daily rhythms of emotions varied depending on demographic variables. Gender was correlated with the frequencies of gratitude and the daily rhythms of anger. As the grade increased, the frequency of emotion words in most subcategories in TTs decreased and the fluctuation in daily rhythms became smaller. There was no significant difference in the frequency and daily rhythm of emotion words used in TTs based on having had a left-behind experience. The results of the present study provided emotion expression in social networks in Chinese collectivist culture. This study added new evidence to support the notion that positive and negative emotions are independent dimensions.


Impedimetric immunosensor for microalbuminuria based on a WS2/Au water-phase assembled nanocomposite.
An electrochemical impedimetric biosensor for human serum albumin (HSA) determination is proposed. The biosensor is based on water-phase assembled nanocomposites made of 2D WS2 nanoflakes and Au nanoparticles (AuNPs). The WS2 has been produced using a liquid-phase exfoliation strategy assisted by sodium cholate, obtaining a water-stable suspension that allowed the straightforward decoration with AuNPs directly in the aqueous phase. The resulting WS2/Au nanocomposite has been characterized by atomic force microscopy and Raman spectroscopy and, then, employed to modify screen-printed electrodes. Good electron-transfer features have been achieved. An electrochemical immunosensing platform has been assembled exploiting cysteamine-glutaraldehyde covalent chemistry for antibody (Ab) immobilization. The resulting immunosensor exhibited good sensitivity for HSA detection (LOD = 2 ng mL-1), with extended linear range (0.005 - 100 µg mL-1), providing a useful analytical tool for HSA determination in urine at relevant clinical ranges for microalbuminuria screening. The HSA quantification in human urine samples resulted in recoveries from 91.8 to 112.4% and was also reproducible (RSD < 7.5%, n = 3), with marked selectivity. This nanocomposite, thanks to the reliable performance and the ease of the assembling strategy, is a promising alternative for electrochemical immunosensing of health relevant markers.


Photocatalytic degradation of methylene blue over nanosized TiO2 particles prepared using the self-propagating high-temperature synthesis method.
In order to reutilize the spent metallic titanium chips, TiO2 photocatalysts were prepared using the self-propagating high-temperature synthesis (SHS) method, and were characterized by N2 gas adsorption, X-ray diffraction, and scanning electron microscope, particle size distribution. Also, their photocatalytic activities were evaluated using methylene blue as a model organic compound. It was confirmed that the crystal structure of TiO2 prepared by SHS method was relatively homogeneous powder of rutile type. Optimum conditions for photocatalytic degradation of methylene blue under UV-C irradiation were methylene blue 9.5 ppm in solution and at amount of TiO2 added of 0.02 g/L. In addition, it was found that the photocatalytic activity for methylene blue degradation over the prepared TiO2 particles was positively related with BET specific surface area.


Revision of the family Gymnophallidae Odhner, 1905 (Digenea) based on morphological and molecular data.
This paper reviews the family Gymnophallidae, recognizing as valid seven genera; four within the subfamily Gymnophallinae: Gymnophallus Odhner, 1900 (syn. Meiogymnophallus Ching, 1965), Paragymnophallus Ching, 1973, Pseudogymnophallus Hoberg, 1981, and Bartolius Cremonte, 2001, and three in the Parvatrematinae: Parvatrema Cable, 1953, Lacunovermis Ching, 1965, and Gymnophalloides Fujita, 1925. Specimens representing one species of each available genus were chosen from those well-described and non controversial species, for which strong morphological information was available, and used for molecular studies (ITS1-5.8S-ITS2-28S rDNA strands were sequenced). The presence or absence of a pars prostatica differentiates between the 2 subfamilies, Gymnophallinae and Parvatrematinae. The characters used to differentiate genera are: location of the ovary (pre-, post- or inter-testicular), size and location of the genital pore (inconspicuous and located at the anterior margin of the ventral sucker, or conspicuous and located at some distance from the anterior margin of ventral sucker), presence of caecal pockets, and presence or absence of ventral pit (a muscular structure which can be either well-developed, similar in size and musculature to the ventral sucker, or be poorly developed). The characters previously used to distinguish among genera that actually should be considered to separate species include: shape of tegument spines (broad, sharp or serrated), presence of lateral projections on the oral sucker (also called papillae or lips), shape of the seminal vesicle (unipartite or bipartite), shape of the prostatic duct (elongate or oval), presence of papillae on the genital pore, shape of the genital atrium (tubular, wide, oval), shape of the vitellaria (follicular in a variable degree, paired or single), shape of the excretory vesicle (V or Y), and extension of uterus (restricted to forebody, at hindbody or extending in both). Additionally, some of these characters may vary with the age of worm. The morphological and molecular information obtained in this study provided strong support for recognizing seven valid genera in the family Gymnophallidae.


Incidence and mortality trends of ovarian cancer in central Serbia.
Ovarian cancer (OC) is the most fatal cancer in females. The objective of this paper was to determine the incidence and mortality trends of OC in central Serbia from 1999 to 2003. Data about all new cases and deaths of OC were obtained from the Serbian Cancer Registry. Data were analyzed for the central of Serbia which encompasses the territory of Serbia without its northern and southern regions. Data of the female population were obtained from the population censuses in the years 1991, 2002 and 2011. World population was used as a standard. Trend and annual percentage change (APC) of the incidence and mortality rate with corresponding 95% confidence intervals (CI) were calculated by performing jointpoint regression. Jointpoint analysis showed increased incidence trend of annual standardized rate (ASR) for OC from 1999 to 2013 with APC 0.3% (95%CI: 0.3, 0.8). Significantly increased trend in OC mortality was recorded continuously from 1999 to 2007 with APC 2.25% (95% CI: 0.9, 3.6). Decreased mortality trend was observed in the period 2010- 2013 with APC -7.34% (95%CI:-15.8, 2.0). The majority of the new cases of OC were aged 40-74 (78.7%). OC was the sixth most common cancer of all cancers in females and the sixth most common cause of cancer death in females. During 1999-2013 there was an increasing trend of incidence of OC. In 1999-2007 there was a significant increasing mortality trend and non-significant decrease of the trend from 2010 to 2013 in central Serbia. The incidence and mortality rates of OC in central Serbia were higher than the corresponding rates in neighboring countries.


Multidimensional fractionation is a requirement for quantitation of Golgi-resident glycosylation enzymes from cultured human cells.
Glycosylation results from the concerted action of glycosylation enzymes in the secretory pathway. In general, gene expression serves as the primary control mechanism, but post-translational fine-tuning of glycosylation enzyme functions is often necessary for efficient synthesis of specific glycan epitopes. While the field of glycomics has rapidly advanced, there lacks routine proteomic methods to measure expression of specific glycosylation enzymes needed to fill the gap between mRNA expression and the glycomic profile in a "reverse genomics" workflow. Toward developing this workflow we enriched Golgi membranes from two human colon cancer cell lines by sucrose density centrifugation and further mass-based fractionation by SDS-PAGE. We then applied mass spectrometry to demonstrate a doubling in the number of Golgi resident proteins identified, compared to the unenriched, low speed centrifuged supernatant of lysed cells. A total of 35 Golgi-resident glycosylation enzymes, of which 23 were glycosyltransferases, were identified making this the largest protein database so far of Golgi resident glycosylation enzymes experimentally identified in cultured human cells. We developed targeted mass spectrometry assays for specific quantitation of many of these glycosylation enzymes. Our results show that alterations in abundance of glycosylation enzymes at the protein level were generally consistent with the resultant glycomic profiles, but not necessarily with the corresponding glycosyltransferase mRNA expression as exemplified by the case of O-glycan core 1 T synthase.


Serological analysis of the deoxyribonucleic acid polymerase of avian oncornaviruses. II. Comparison of avian deoxyribonucleic acid polymerases.
Monospecific antiserum prepared against the isolated deoxyribonucleic acid (DNA) polymerase of avian myeloblastosis virus (AMV) neutralized the endogenous ribonucleic acid-instructed DNA polymerase activity of detergent-disrupted virus. The viral polymerase was serologically unrelated to the seven major structural polypeptides of AMV. Furthermore, the viral enzyme was distinguished from normal cellular DNA polymerases by serological criteria; thus, antiserum against the viral enzyme neutralized its homologous antigen but not normal cellular DNA polymerases. Neutralization by antibody of viral DNA polymerase activity was observed with all avian leukemia-sarcoma viruses tested, irrespective of viral antigenic subtype. The DNA polymerase activity of avian reticuloendotheliosis virus, and of a variety of mammalian oncornaviruses, was not neutralized by antisera against the AMV polymerase. Immunological analysis of the RSValpha(O) mutant, which is deficient in DNA polymerase activity, shows this mutant to lack demonstrable polymerase antigen. Viral polymerase was identified by immunofluorescence as a cytoplasmic constituent in virus-producing chicken cells; polymerase antigen was not detected in uninfected (gs(-)) chicken cells.


A 10-year experience in nasal reconstruction with the three-stage forehead flap.
Because of its ideal color and texture, forehead skin is acknowledged as the best donor site with which to resurface the nose. However, all forehead flaps, regardless of their vascular pedicles, are thicker than normal nasal skin. Stiff and flat, they do not easily mold from a two-dimensional to a three-dimensional shape. Traditionally, the forehead is transferred in two stages. At the first stage, frontalis muscle and subcutaneous tissue are excised distally and the partially thinned flap is inset into the recipient site. At a second stage, 3 weeks later, the pedicle is divided. However, such soft-tissue "thinning" is limited, incomplete, and piecemeal. Flap necrosis and contour irregularities are especially common in smokers and in major nasal reconstructions. To overcome these problems, the technique of forehead flap transfer was modified. An extra operation was added between transfer and division.At the first stage, a full-thickness forehead flap is elevated with all its layers and is transposed without thinning except for the columellar inset. Primary cartilage grafts are placed if vascularized intranasal lining is present or restored. Importantly, at the first stage, skin grafts or a folded forehead flap can be used effectively for lining. A full-thickness skin graft will reliably survive when placed on a highly vascular bed. A full-thickness forehead flap can be folded to replace missing cover skin, with a distal extension, in continuity, to supply lining. At the second stage, 3 weeks later during an intermediate operation, the full-thickness forehead flap, now healed to its recipient bed, is physiologically delayed. Forehead skin with 3 to 4 mm of subcutaneous fat (nasal skin thickness) is elevated in the unscarred subcutaneous plane over the entire nasal inset, except for the columella. Skin grafts or folded flaps integrate into adjacent normal lining and can be completely separated from the overlying cover from which they were initially vascularized. If used, a folded forehead flap is incised free along the rim, completely separating the proximal cover flap from the distal lining extension. The underlying subcutaneous tissue, frontalis muscle, and any previously positioned cartilage grafts are now widely exposed, and excess soft tissue can be excised to carve an ideal subunit, rigid subsurface architecture. Previous primary cartilage grafts can be repositioned, sculpted, or augmented, if required. Delayed primary cartilage grafts can be placed to support lining created from a skin graft or a folded flap. The forehead cover skin (thin, supple, and conforming) is then replaced on the underlying rigid, recontoured, three-dimensional recipient bed. The pedicle is not transected. At a third stage, 3 weeks later (6 weeks after the initial transfer), the pedicle is divided. Over 10 years in 90 nasal reconstructions for partial and full-thickness defects, the three-stage forehead flap technique with an intermediate operation was used with primary and delayed primary grafts, and with intranasal lining flaps (n = 15), skin grafts (n = 11), folded forehead flaps (n = 3), turnover flaps (n = 5), prefabricated flaps (n = 4), and free flaps for lining (n = 2). Necrosis of the forehead flap did not occur. Late revisions were not required or were minor in partial defects. In full-thickness defects, a major revision and more than two minor revisions were performed in less than 5 percent of patients. Overall, the aesthetic results approached normal. The planned three-stage forehead flap technique of nasal repair with an intermediate operation (1) transfers subtle, conforming forehead skin of ideal thinness for cover, with little risk of necrosis; (2) uses primary and delayed primary grafts and permits modification of initial cartilage grafts to correct failures of design, malposition, or scar contraction before flap division; (3) creates an ideal, rigid subsurface framework of hard and soft tissue that is reflected through overlying skin and blends well into adjacent recipient tissues; (4) expands the application of lining techniques to include the use of skin grafts for lining at the first stage, or as a "salvage procedure" during the second stage, and also permits the aesthetic use of folded forehead flaps for lining; (5) ensures maximal blood supply and vascular safety to all nasal layers; (6) provides the surgeon with options to salvage reconstructive catastrophes; (7) improves the aesthetic result while decreasing the number and difficulty of revision operations and overall time for repair; and (8) emphasizes the interdependence of anatomy (cover, lining, and support) and provides insight into the nature of wound injury and repair in nasal reconstruction.


First Report of Lasiodiplodia pseudotheobromae Causing Postharvest Fruit Rot on Indian Jujube in China.
Indian jujube (Ziziphus mauritiana Lamarck), is one of the most popular fruit crops in South China. In March 2023, a fruit rot of indian jujube with about 5% disease incidence was observed in two supermarkets of Nanchang City, Jiangxi Province, China. Initially, the symptoms appeared as slightly brown spots on the fruit surface, with disease progression, the lesions gradually expanded and covered with a layer of hyphae. Small pieces (3 to 4 mm2) from the periphery of 15 diseased fruit were surface disinfected using 1% sodium hypochlorite for 30 s, rinsed three times in sterilized distilled water, air dried, and then aseptically placed onto potato dextrose agar (PDA) media and incubated at 25°C for three days. A total of ten single spore isolates with similar morphology were obtained. Colonies of these consisted of initially white, gradually turning gray and eventually becoming black, and aerial hyphae were dense and fluffy. Conidiogenous cells were smooth, hyaline, cylinder-shaped, and holoblastic. Conidia were ellipsoidal, top and base-rounded, and thick-walled, immature conidia were colorless, hyaline, and aseptate, compared with dark brown color of the mature conidia, which were one-septate with longitudinal striations, ranging in size from 22.8 to 31.8 (mean 27.6) µm in length and 12.2 to 20 (mean 14.6) µm in width. The morphological characteristics were consistent with the characteristics of the Lasiodiplodia species (Phillips et al. 2013). To accurately identify the strain, three representative isolates, namely JFRL 03-1147, JFRL 03-1148, and JFRL 03-1149, were selected for further identification. The internal transcribed spacers (ITS), translation elongation factor 1-alpha (TEF1-α), and beta-tubulin (TUB2) genes/regions were amplified and sequenced using primers ITS1/ITS4, EF1-688F/EF1-1251R, and Bt2a/Bt2b, respectively (Chen et al. 2021). These nucleotide sequences were deposited in GenBank with accession numbers OQ804425-OQ804427 (ITS), OQ818097-OQ818099 (TEF1-α), and OQ818100-OQ818102 (TUB2). A BLASTn homology search for these nucleotides showed 99-100% identity to ITS (EF622077, 487 nt/487 nt), TEF1-α (EF622057, 306 nt/307 nt) and TUB2 (EU673111, 434 nt/434 nt) sequences of Lasiodiplodia pseudotheobromae CBS 116459 (ex-type). The maximum likelihood analyses were performed for the combined ITS, TEF1-α and TUB2 data set using IQtree web server (Trifinopoulos et al. 2016). The phylogenetic tree showed that the three isolates clustered with Lasiodiplodia pseudotheobromae in a clade with 99% bootstrap support. Therefore, the fungus was identified as L. pseudotheobromae based on morphological and molecular characteristics. To evaluate pathogenicity, 4 healthy fruits of indian jujube were surface sterilized with 75% ethanol and wounded by sterile needle, and a 5-mm-diameter agar with 5-days-old mycelium of the isolate JFRL 03-1148 cultured on PDA at 25°C was put on the wound. Another set of 4 fruits was inoculated with sterile agar plugs as controls. The fruits were cultured at 25℃ and 85% relative humidity, and the test was repeated twice. These fruits inoculated with L. pseudotheobromae showed similar rot symptoms after 3 days, while the control group remained asymptomatic. To fulfill Koch's postulates, the pathogen was re-isolated from the inoculated fruits and confirmed as L. pseudotheobromae by morphological and molecular analysis. L. pseudotheobromae has previously been reported causing fruit rot on citrus, mango and papaya (Alam et al. 2021; Chen et al. 2021; Netto et al. 2014). But to our knowledge, this is the first report of L. pseudotheobromae caused postharvest fruit rot on indian jujube in China. Therefore, managers should pay more attention to postharvest fruit rot disease caused by L. pseudotheobromae, and formulate appropriate disease control measures to reduce its losses.


Downregulation of feline sarcoma-related protein inhibits cell migration, invasion and epithelial-mesenchymal transition via the ERK/AP-1 pathway in bladder urothelial cell carcinoma.
Feline sarcoma-related protein (Fer) is a nuclear and cytoplasmic non-receptor protein tyrosine kinase and Fer overexpression is associated with various biological processes. However, the clinicopathological characteristics and molecular mechanisms of Fer expression in bladder urothelial cell carcinoma (UCC) have yet to be elucidated. The present study demonstrated that Fer was significantly upregulated in bladder UCC tissues and cell lines. A clinicopathological analysis suggested that Fer expression was significantly associated with tumor stage, histological grade and lymph node status, and Fer expression was a prognostic factor for overall survival in a multivariate analysis. Furthermore, small interfering RNA (siRNA) was used to silence the expression of the Fer gene in human bladder UCC T24 cells, and was shown to significantly reduce the migration and invasion of the cells. It was also observed that Fer-siRNA caused the T24 cells to acquire an epithelial cobblestone phenotype, and was able to reverse the epithelial-mesenchymal transition of the cells. Subsequently, Fer-knockdown was shown to deactivate the extracellular signal-regulated kinase/activator protein-1 signaling pathway in T24 cells. These results indicated, for the first time, that Fer has a critical role in bladder UCC progression and may be a potential therapeutic target for bladder UCC metastasis.


InAsP quantum dot lasers grown by MOVPE.
We report on InAsP quantum dot lasers grown by MOVPE for 730-780 nm wavelength emission and compare performance with InP dot samples grown under similar conditions and with similar structures. 1-4 mm long, uncoated facet InAsP dot lasers emit between 760 and 775 nm and 2 mm long lasers with uncoated facets have threshold current density of 260 Acm(-2), compared with 150 Acm(-2) for InP quantum dot samples, which emit at shorter wavelengths, 715-725 nm. Pulsed lasing is demonstrated for InAsP dots up to 380 K with up to 200 mW output power. Measured absorption spectra indicate the addition of Arsenic to the dots has shifted the available transitions to longer wavelengths but also results in a much larger degree of spectral broadening. These spectra and transmission electron microscopy images indicate that the InAsP dots have a much larger degree of inhomogeneous broadening due to dot size variation, both from layer to layer and within a layer.


Contrast-Enhanced Ultrasound (CEUS) in Non-Traumatic Abdominal Emergencies.
Conventional ultrasound imaging (US) is the first-line investigation in acute non-traumatic abdominal emergencies, but sometimes it needs further examinations, such as computed tomography (CT), to reach a certain diagnosis. Contrast-enhanced ultrasound (CEUS), through injection of contrast medium, may provide the radiologist with additional information that could not be investigated with baseline US. It could help reach a diagnosis and rapidly determine the proper therapy in an emergency setting. The purpose of this review is to explain and illustrate the various possibilities and limitations of CEUS in acute non-traumatic abdominal diseases, in particular acute inflammation, parenchymal infarcts, and hemorrhages.


[Absence of asymptomatic malaria in schoolchildren of Quibdó, Chocó].
Asymptomatic malaria is characteristic of high intensity transmission areas in Africa but unusual in low transmission areas in Latin America. Nevertheless, asymptomatic malaria has been reported to be frequent in areas in Latin America with high and moderate intensity of transmission. Asymptomatic malaria can affect both individuals who carry parasites and are cryptic carrier reservoirs for the community. Individuals chronically infected with malaria parasites are usually unidentifiable by most malaria control programmes. In order to identify whether asymptomatic individuals harboring malaria parasites are an important reservoir of infection in Quibdó, Chocó, the prevalence of asymptomatic malaria was assessed in schoolchildren. This study was part of a major study of the epidemiology of malaria in Quibdó. A total of 255 children from 5 schools were examined, of which 223 were included in the analysis. Children reported headache (34%), cough (32%), and diarrhoea (9%). None of the children presented a positive thick smear. In addition, IFA tests in a subsample of 25 children were negative. By these criteria, the prevalence of asymptomatic malaria in Quibdó schoolchildren is 0% (95%C.I.: 0.0-1.4). Although asymptomatic malaria in adults possibly occurs, a very low prevalence is predicted.


Optimizing Deep Learning-Based Segmentation of Densely Packed Cells using Cell Surface Markers.
Spatial molecular profiling depends on accurate cell segmentation. Identification and quantitation of individual cells in dense tissues, e.g. highly inflamed tissue caused by viral infection or immune reaction, remains a challenge. We first assess the performance of 18 deep learning-based cell segmentation models, either pre-trained or trained by us using two public image sets, on a set of immunofluorescence images stained with immune cell surface markers in skin tissue obtained during human herpes simplex virus (HSV) infection. We then further train eight of these models using up to 10,000+ training instances from the current image set. Finally, we seek to improve performance by tuning parameters of the most successful method from the previous step. The best model before fine-tuning achieves a mean Average Precision (mAP) of 0.516. Prediction performance improves substantially after training. The best model is the cyto model from Cellpose. After training, it achieves an mAP of 0.694; with further parameter tuning, the mAP reaches 0.711. Selecting the best model among the existing approaches and further training the model with images of interest produce the most gain in prediction performance. The performance of the resulting model compares favorably to human performance. The imperfection of the final model performance can be attributed to the moderate signal-to-noise ratio i the imageset.


Structural basis of charge transfer complex formation by riboflavin bound to 6,7-dimethyl-8-ribityllumazine synthase.
The amino acid residue tryptophan 27 of 6,7-dimethyl-8-ribityllumazine synthase of the yeast Schizosaccharomyces pombe was replaced by tyrosine. The structures of the W27Y mutant protein in complex with riboflavin, the substrate analogue 5-nitroso-6-ribitylamino-2,4(1H,3H)-pyrimidinedione, and the product analogue 6-carboxyethyl-7-oxo-8-ribityllumazine, were determined by X-ray crystallography at resolutions of 2.7-2.8 A. Whereas the indole system of W27 forms a coplanar pi-complex with riboflavin, the corresponding phenyl ring in the W27Y mutant establishes only peripheral contact with the heterocyclic ring system of the bound riboflavin. These findings provide an explanation for the absence of the long wavelength shift in optical absorption spectra of riboflavin bound to the mutant enzyme. The structures of the mutants are important tools for the interpretation of the unusual physical properties of riboflavin in complex with lumazine synthase.


It Is Imperative to Establish a Pellucid Definition of Chimeric RNA and to Clear Up a Lot of Confusion in the Relevant Research.
There have been tens of thousands of RNAs deposited in different databases that contain sequences of two genes and are coined chimeric RNAs, or chimeras. However, "chimeric RNA" has never been lucidly defined, partly because "gene" itself is still ill-defined and because the means of production for many RNAs is unclear. Since the number of putative chimeras is soaring, it is imperative to establish a pellucid definition for it, in order to differentiate chimeras from regular RNAs. Otherwise, not only will chimeric RNA studies be misled but also characterization of fusion genes and unannotated genes will be hindered. We propose that only those RNAs that are formed by joining two RNA transcripts together without a fusion gene as a genomic basis should be regarded as authentic chimeras, whereas those RNAs transcribed as, and cis-spliced from, single transcripts should not be deemed as chimeras. Many RNAs containing sequences of two neighboring genes may be transcribed via a readthrough mechanism, and thus are actually RNAs of unannotated genes or RNA variants of known genes, but not chimeras. In today's chimeric RNA research, there are still several key flaws, technical constraints and understudied tasks, which are also described in this perspective essay.


St John's wort (Hypericum perforatum) modulates evoked potentials in guinea pig hippocampal slices via AMPA and GABA receptors.
The effects of an ethanolic extract of the plant Hypericum perforatum L. (St John's wort) (HYP) and its hydrosoluble fraction (HYPWS) on electrically evoked population spikes and fEPSP were investigated in this study. Concentration dependent (10(-6) to 10(-4) g/l) excitatory effects were found. Above concentrations of 10(-3) g/l, HYP reduced the evoked responses, whereas HYPWS further increased them. Paired pulse facilitation was unaffected with HYPWS (10(-4) to 10(-2) g/l). The excitatory effects of HYPWS were amplified by the GABA(A) and GABA(B) receptor antagonists bicuculline and phaclofen, respectively. These excitations were antagonised by the AMPA receptor antagonist CNQX. Excitations caused by hypericum were not antagonised by the NMDA receptor antagonists D-APV and MK801, the metabotropic glutamate receptor (type I and II) antagonist MCPG, or the L-type calcium channel blocker verapamil. Hypericin and hyperforin, two components of H. perforatum, were found not to be responsible for the excitatory effects of the extract.


Molecular screening on a compact disc.
A method is described to screen the recognition between small molecule ligands and biomolecules using a conventional compact disc (CD) player. A procedure was developed to attach ligands to the reading face of a CD by activating the terminus of polycarbonate, a common polymer composite within the reading face of a CD. Terminal residues of the polycarbonate surface 1 were phosphorylated by reaction with ethyl-(N,N)-diisopropylamine-buffered dichloro-(N,N)-diisopropylaminophosphate to yield surface-bound chlorophosphate 2. Ligands containing a primary alcohol were condensed with 2 providing a polycarbonate capped with phosphodiester linked ligands 3-6. Displays were generated on the surface of a CD by printing tracks of ligands 3-6 on the disc with an inkjet printer. Using this method, discs were created with entire assemblies of ligand molecules distributed into separate blocks. A molecular array was developed by assembling collections of these blocks to correlate with the CDROM-XA formatted data stored within the digital layer of the disc. Regions of the disc containing a given ligand or set of ligands was marked by its spatial position using the tracking and header information. Recognition between surface expressed ligands and biomolecules was screened by an error determination routine.


[An elderly patient with bleeding from the alimentary tract caused by aberrant pancreas of the small intestine].
A 71-year-old woman was admitted to hospital because of malaise and bloody stool. Laboratory findings consistently showed anemia (Hb 9.2 g/dl) and occult blood in the stool. Although barium series and endoscopy of the upper and lower intestinal tructs were carried out, there was no evidence of bleeding from the gastrointestinal tract 99mTcO4- scintigraphy, which was performed to exclude bleeding from Meckel's diverticulum, also did not locate a significant lesion. Angiographic imaging of the superior mesenteric arteries (SMA) was performed to exclude lesions such as small intestine tumors with extraluminal growth and vascular abnormalities such as A-V malformation and it revealed the round encasement of arteries in the peripheral SMA region, strongly suggestive of a small intestine tumor. Surgery was performed and an extraluminally protruding tumor was found in the small intestine. The excised tumor was 4 x 3 x 3.5 cm in size, are was diagnosed histologically as aberrant pancreas. The postoperative laboratory findings showed that the anemia had improved and occult blood was not detected in the stools. Although aberrant pancreas of the small intestine is a common benign tumor, it is a very unusual cause of bleeding from the alimentary tract.


Mechanisms of Regeneration and Fibrosis in the Endometrium.
The uterine lining (endometrium) regenerates repeatedly over the life span as part of its normal physiology. Substantial portions of the endometrium are shed during childbirth (parturition) and, in some species, menstruation, but the tissue is rapidly rebuilt without scarring, rendering it a powerful model of regeneration in mammals. Nonetheless, following some assaults, including medical procedures and infections, the endometrium fails to regenerate and instead forms scars that may interfere with normal endometrial function and contribute to infertility. Thus, the endometrium provides an exceptional platform to answer a central question of regenerative medicine: Why do some systems regenerate while others scar? Here, we review our current understanding of diverse endometrial disruption events in humans, nonhuman primates, and rodents, and the associated mechanisms of regenerative success and failure. Elucidating the determinants of these disparate repair processes promises insights into fundamental mechanisms of mammalian regeneration with substantial implications for reproductive health.


Spin-phonon coupling in a double-stranded model of DNA.
We address the electron-spin-phonon coupling in an effective model Hamiltonian for DNA to assess its role in spin transfer involved in the Chiral-Induced Spin Selectivity (CISS) effect. The envelope function approach is used to describe semiclassical electron transfer in a tight-binding model of DNA at half filling in the presence of intrinsic spin-orbit coupling. Spin-phonon coupling arises from the orbital-configuration dependence of the spin-orbit interaction. We find spin-phonon coupling only for the acoustic modes, while the optical modes exhibit electron-phonon interaction without coupling to spin. We derive an effective Hamiltonian whose eigenstates carry spin currents that are protected by spin-inactive stretching optical modes. As optical phonons interact more strongly than acoustic phonons, side buckling and tilting optical base modes will be more strongly associated with decoherence, which allows for the two terminal spin filtering effects found in CISS.


Characterization of the role of distinct plasma cell-free DNA species in age-associated inflammation and frailty.
Plasma cell-free DNA (cf-DNA) has recently emerged as a potential biomarker of aging, reflecting systemic inflammation, and cell death. In addition, it has been suggested that cf-DNA could promote autoinflammation. Because the total cf-DNA pool comprises different cf-DNA species, we quantified the plasma levels of gene-coding cf-DNA, Alu repeat cf-DNA, mitochondrial DNA (mtDNA) copy number, and the amounts of unmethylated and total cf-DNAs. We identified the relationships between these cf-DNA species and age-associated inflammation, immunosenescence, and frailty. Additionally, we determined the cf-DNA species-specific transcriptomic signatures in blood mononuclear cells to elucidate the age-linked leukocyte responses to cf-DNA. The study population consisted of n = 144 nonagenarian participants of the Vitality 90+ Study and n = 30 young controls. In the nonagenarians, higher levels of total and unmethylated cf-DNAs were associated with systemic inflammation and increased frailty. The mtDNA copy number was also directly correlated with increased frailty but not with inflammation. None of the cf-DNA species were associated with immunosenescence. The transcriptomic pathway analysis revealed that higher levels of total and unmethylated cf-DNAs were associated with immunoinflammatory activation in the nonagenarians but not in the young controls. The plasma mtDNA appeared to be inert in terms of inflammatory activation in both the nonagenarians and young controls. These data demonstrate that the plasma levels of total and unmethylated cf-DNA and the mtDNA copy number could serve as biomarkers of frailty. In addition, we suggest that circulating self-DNA, assessed as total or unmethylated cf-DNA, might aggravate immunoinflammatory reactivity in very old individuals.


Next generation sequencing for diagnosis of central nervous system aspergillosis in liver transplant recipients.
Fungal encephalitis is uncommon and sometimes fatal in liver transplant (LT) recipients. Early diagnosis of central nervous system (CNS) fungal infections, especially aspergillosis, is difficult based on routine tests of cerebrospinal fluid (CSF) alone. Next-generation sequencing (NGS) as a new tool may help in this respect. Shotgun metagenomics was used to detect pathogens in CSF of patients, who were clinically suspected of CNS infection. Sequencing was performed at BGIseq-50 platform (BGI, Shenzhen). NGS technique identified Aspergillus in CSF of 5 patients, who were suspected of CNS infection, although clinical symptoms of these patients varied dramatically. The resulting sequence reads corresponding to Aspergillus species ranged from 2 to 25, with genomic coverage ranging from 0.0003% to 0.0036%. Rapid identification of Aspergillus enabled early appropriate antifungal therapy, although 4 patients eventually died of severe infection. This is the first study to highlight the utility of NGS in early diagnosis of CNS aspergillosis in LT recipients. This new tool may be helpful in improving the diagnosis of CNS aspergillosis.


Tau potentiates nerve growth factor-induced mitogen-activated protein kinase signaling and neurite initiation without a requirement for microtubule binding.
Microtubule-associated protein Tau is known to bind to and stabilize microtubules, thereby regulating microtubule dynamics. However, recent evidence has indicated that Tau can also interact with various components of intracellular signaling pathways, leading to the possibility that Tau might have a role in signal transduction. Here we provide evidence that during growth factor stimulation of neuronal cells, Tau has functions in advance of the neurite elongation stage. Using Tau-depleted neuronal cell lines, we demonstrate that Tau is required for neurite initiation in a manner that does not involve its microtubule binding function. In addition, we demonstrate that Tau potentiates AP-1 transcription factor activation in response to nerve growth factor (NGF). The effect of Tau on AP-1 activation is mediated through its ability to potentiate the activation of mitogen-activated protein kinase (MAPK), which occurs in response to both NGF and epidermal growth factor. Phosphorylation of Tau at Thr-231 also occurs in response to NGF and is required for Tau to impact on MAPK signaling, whereas the ability of Tau to bind to microtubules is not required. Together, these findings indicate a new functional role for Tau in early neuronal development independent of its established role in microtubule stabilization.


Dental and bone abnormalities in patients with familial polyposis coli.
Dental and bone abnormalities of the maxilla and mandible are present in approximately 80% of patients with familial polyposis coli. The dental abnormalities include impacted teeth (other than third molars), supernumerary teeth, congenitally missing teeth, fused roots of first and second molars, and unusually long and tapered roots of posterior teeth. The bone lesions consist mostly of osteomas, either isolated or in clusters, in the maxilla and mandible or of exostoses with lateral and/or lingual extensions. Since dental and bone abnormalities are already present early in life there is a strong suggestion that they may be used as diagnostic features in the recognition of familial polyposis coli.


Selective estrogen-receptor modulators and antihormonal resistance in breast cancer.
Selective estrogen-receptor (ER) modulators (SERMs) are synthetic nonsteroidal compounds that switch on and switch off target sites throughout the body. Tamoxifen, the pioneering SERM, blocks estrogen action by binding to the ER in breast cancers. Tamoxifen has been used ubiquitously in clinical practice during the last 30 years for the treatment of breast cancer and is currently available to reduce the risk of breast cancer in high-risk women. Raloxifene maintains bone density (estrogen-like effect) in postmenopausal osteoporotic women, but at the same time reduces the incidence of breast cancer in both high- and low-risk (osteoporotic) postmenopausal women. Unlike tamoxifen, raloxifene does not increase the incidence of endometrial cancer. Clearly, the simple ER model of estrogen action can no longer be used to explain SERM action at different sites around the body. Instead, a new model has evolved on the basis of the discovery of protein partners that modulate estrogen action at distinct target sites. Coactivators are the principal players that assemble a complex of functional proteins around the ligand ER complex to initiate transcription of a target gene at its promoter site. A promiscuous SERM ER complex creates a stimulatory signal in growth factor receptor-rich breast or endometrial cancer cells. These events cause drug-resistant, SERM-stimulated growth. The sometimes surprising pharmacology of SERMs has resulted in a growing interest in the development of new selective medicines for other members of the nuclear receptor superfamily. This will allow the precise treatment of diseases that was previously considered impossible.


Bcl6 acts as an amplifier for the generation and proliferative capacity of central memory CD8+ T cells.
Central memory CD8(+) T cells (T(CM)) are considered to be more efficient than effector ones (T(EM)) for mediating protective immunity. The molecular mechanism involved in the generation of these cells remains elusive. Because Bcl6 plays a role in the generation and maintenance of memory CD8(+) T cells, we further examined this role in the process in relation to T(CM) and T(EM) subsets. In this study, we show that T(CM) and T(EM) were functionally identified in CD62L(+) and CD62L(-) memory (CD44(+)Ly6C(+)) CD8(+) T cell subsets, respectively. Although T(CM) produced similar amounts of IFN-gamma and IL-2 to T(EM) after anti-CD3 stimulation, the cell proliferation capacity after stimulation and tissue distribution profiles of T(CM) differed from those of T(EM). Numbers of T(CM) were greatly reduced and elevated in spleens of Bcl6-deficient and lck-Bcl6 transgenic mice, respectively, and those of T(EM) were constant in nonlymphoid organs of these same mice. The majority of Ag-specific memory CD8(+) T cells in spleens of these mice 10 wk after immunization were T(CM), and the number correlated with Bcl6 expression in T cells. The proliferation of Ag-specific memory CD8(+) T cells upon secondary stimulation was dramatically up-regulated in lck-Bcl6 transgenic mice, and the adoptive transfer experiments with Ag-specific naive CD8(+) T cells demonstrated that some of the up-regulation was due to the intrinsic effect of Bcl6 in the T cells. Thus, Bcl6 is apparently a crucial factor for the generation and secondary expansion of T(CM).


High-density lipoprotein response to alcohol consumption and abstinence as an indicator of liver function in alcoholic patients.
A study of 36 alcoholic men admitted to hospital when intoxicated was undertaken to confirm the value of changes in the level of high-density lipoprotein cholesterol (HDL) as an indicator of liver function in patients with chronic alcoholism. In the patients without severe liver disease the HDL level was high after the recent consumption of alcohol and usually dropped by 0.2 mmol/L or more after 1 or 2 weeks of abstinence. In contrast, in the patients with severe alcoholic liver disease the HDL level was initially low and generally remained low after abstinence.


Volatile compounds and sensory properties of Montasio cheese made from the milk of Simmental cows grazing on alpine pastures.
The aim of this study was to analyze the volatile compounds, physicochemical characteristics, and sensory properties of Montasio, a semicooked pressed cheese, produced from the milk of the dual-purpose Italian Simmental cows grazing on alpine pastures. A total of 72 cows grazing on 2 pastures, which differed in botanical composition (nutrient-rich pasture vs. nutrient-poor pasture), received 2 different levels of supplementation (3.0 vs 1.5 kg/head per day). The experimental cheeses were produced from whole, raw milk and ripened for 60 d. Sixty-one volatile compounds, including alcohols (11), aldehydes (6), ketones (10), lactones (2), esters (6), hydrocarbons (3), carboxylic acids (6), phenolic compounds (4), monoterpenes (7), sesquiterpenes (1), sulfur compounds (4), and amines (1), were detected. The main families in terms of relative weight appeared to be carboxylic acids, esters, and alcohols. A panel of trained assessors described the experimental cheeses as having an intense color; small and evenly distributed eyes; an intense odor and flavor of milk-sour, milk, and cow; and a tender and creamy texture. The pasture type affected the volatile fraction, particularly ketones, phenolic compounds, and terpenes, which are overall higher in nutrient-poor pastures. A slight effect on the sensory analyses, in particular the effect of the cow attribute on odor and flavor, was perceived by the panelists. The cheeses produced on nutrient-rich pasture had higher b* (yellowness) index. These results were consistent with the color evaluation of the sensory panel. In addition, the pasture affected some textural attributes (adhesivity, creaminess, and granules) as perceived by the panelists. Concentrate supplementation, which is required to meet the feeding requirements of grazing cows, had no clear effect on either the volatile compounds or the sensory properties of the cheeses. Thus, at least within levels of integration adopted, it is expected not to alter the organoleptic characteristics of this product.


[Pneumatosis cystoides intestinalis with a gastric ulcer and the stenosis of the pylorus].
A health check up in a 31-year-old man revealed free air under the diaphragm by a chest X-ray. The CT showed marked cystic emphysema along the small intestinal wall, as well as thickening and stenosis of the pyloric wall of stomach. Therefore, we suspected pneumatosis cystoides intestinalis (PCI) with stenosis of the pylorus. Since no perforation of the intestinal tract was diagnosed, it was preserved. Upper G.I. endoscopy showed H2 stage gastric ulcer in the posterior wall of the antrum. Eventually, a diagnosis of PCI with gastric ulcer and stenosis of the pylorus was, which we preserved. We report this rare case here.


Tissue Doppler imaging in hypertrophic cardiomyopathy: impact of intraventricular obstruction on longitudinal left ventricular function.
In non-obstructive hypertrophic cardiomyopathy, tissue Doppler imaging of the mitral annulus shows severe systolic and diastolic dysfunction, with marked heterogeneity and asynchrony. In obstructive forms, the complexity of pathophysiological interactions makes conventional echocardiographic functional assessment extremely difficult and complex. To study longitudinal left ventricular function with tissue Doppler imaging in the obstructive forms of hypertrophic cardiomyopathy. Twenty-six patients with hypertrophic obstructive cardiomyopathy and 23 patients with the non-obstructive form of the disease, matched by age, were studied with pulsed tissue Doppler imaging of the 4 sides of the mitral annulus (septal, lateral, inferior, anterior) in 4 and 2 chamber views. In each wave (systolic-s, rapid filling-e, atrial contraction-a) we analyzed velocities, time intervals and velocity-time integrals, as well as heterogeneity and asynchrony indexes. Data were compared between the different sides in each group, between groups and with conventional Doppler data. In contrast to the non-obstructive forms, patients with intraventricular obstruction showed: Systolic function: similar velocities and integrals, the relations between the different sides of the annulus usually being preserved; longer isovolumic contraction time, time to peak s and PEP/LVET. Diastolic function: similar rapid filling and e/a velocities and integrals, lower atrial contraction velocity and integral, similar number of sides with e/a higher than or equal to 1 on the lateral and inferior side of the annulus; similar diastolic time intervals, except diastolic time. This study shows that the presence of dynamic intraventricular obstruction and the loading conditions of obstructive forms of hypertrophic cardiomyopathy do not significantly influence most annular tissue Doppler imaging parameters, showing the relative load independence of the technique. So, in obstructive hypertrophic cardiomyopathy patients: 1--Longitudinal systolic function (velocities) is similar to the non-obstructive forms--longitudinal systolic dysfunction. 2--Longitudinal diastolic function (velocities and time intervals) is similar to the non-obstructive forms--longitudinal diastolic dysfunction. 3--Left atrial dysfunction is more severe than in non-obstructive forms. 4--The inferior and lateral sides of the annulus should be those selected in order to identify pseudonormalization of the transmitral flow.


Natural history of fetal ventriculomegaly.
The natural history of in utero ventriculomegaly was defined by a retrospective review of the outcome of 47 fetuses evaluated during a 5-year period by the Fetal Treatment Program at the University of California. In 20 fetuses, a diagnosis of ventriculomegaly associated with other severe abnormalities was made early in pregnancy. Termination of pregnancy was elected in 19 of 20 cases, and no fetus survived. In five fetuses, the diagnosis was made late in pregnancy and was associated with severe abnormalities. Fetuses were handled in a routine obstetric fashion and none survived. Of the other 22 fetuses 19 had stable and two had progressive ventriculomegaly; in one case, ventriculomegaly resolved in utero. Nineteen of these fetuses have survived, 13 with normal intellectual development and six with moderately to severely delayed development. Associated abnormalities were detected with ultrasonography in 74% of fetuses; there was a 20% false-negative rate of detection. Ventriculomegaly was isolated and progressive in two fetuses. In both cases, fetuses were delivered at term, and postnatally a shunting procedure was performed. Both children are neurologically normal. From our results and a review of the literature, which supports our findings, we were unable to define a group of fetuses with in utero ventriculomegaly that would benefit from in utero shunting.


Delayed inflammatory reaction to hyaluronic acid (Restylane).
A 45-year-old man received an injection of Restylane (cross-linked hyaluronic acid) to a mid-forehead furrow line in an attempt to reduce its prominence. The injection was uncomplicated and successful in reducing the line. Five months after the injection, he returned with an inflammatory reaction in the area of injection that resolved without treatment over a period of 3 weeks.


Glomerular losartan (DuP 753)-sensitive angiotensin II receptor density is increased in young spontaneously hypertensive rats.
There is increasing evidence that an activated intrarenal renin-angiotensin system (RAS) alters renal hemodynamics and fluid balance and that such events may lead to the development of hypertension. To examine the role of the glomerular RAS in the development of hypertension in the spontaneously hypertensive (SHR) rat, we studied angiotensin (ANG) II receptors in isolated glomeruli from young (4- to 5-wk-old) and adult (10- to 12-wk-old) SHR and from age-matched, normotensive Wistar-Kyoto (WKY) rats. Glomerular ANG II receptor density in young SHR is 3-fold higher than in age-matched WKY rats (2033 +/- 154 versus 742 +/- 151 receptors/microns2; p < 0.05) and 1.5-fold higher than in adult SHR and WKY rats (1128 +/- 85 and 1198 +/- 181 receptors/microns2, respectively; p < 0.05). Additional studies demonstrated that the differences in receptor density are not related to disparity in receptor occupancy and that they are also independent of systemic ANG levels. Suppression of RAS by ANG converting enzyme inhibitors resulted in a 3-fold increase in receptor density in young SHR rats and a 4.5-fold increase in young WKY rats; receptor density remained greater in young SHR rats (5915 +/- 318 versus 3358 +/- 234 receptors/microns2, p < 0.05). Furthermore, competitive binding experiments using the nonpeptide ANG II antagonists losartan (AT1) and PD 123319 (AT2) indicate that the greater ANG II receptor density in the young SHR rats represents an increase in the number of a single population of AT1 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)


Microbial Eukaryotes in Oil Sands Environments: Heterotrophs in the Spotlight.
Hydrocarbon extraction and exploitation is a global, trillion-dollar industry. However, for decades it has also been known that fossil fuel usage is environmentally detrimental; the burning of hydrocarbons results in climate change, and environmental damage during extraction and transport can also occur. Substantial global efforts into mitigating this environmental disruption are underway. The global petroleum industry is moving more and more into exploiting unconventional oil reserves, such as oil sands and shale oil. The Albertan oil sands are one example of unconventional oil reserves; this mixture of sand and heavy bitumen lying under the boreal forest of Northern Alberta represent one of the world's largest hydrocarbon reserves, but extraction also requires the disturbance of a delicate northern ecosystem. Considerable effort is being made by various stakeholders to mitigate environmental impact and reclaim anthropogenically disturbed environments associated with oil sand extraction. In this review, we discuss the eukaryotic microbial communities associated with the boreal ecosystem and how this is affected by hydrocarbon extraction, with a particular emphasis on the reclamation of tailings ponds, where oil sands extraction waste is stored. Microbial eukaryotes, or protists, are an essential part of every global ecosystem, but our understanding of how they affect reclamation is limited due to our fledgling understanding of these organisms in anthropogenically hydrocarbon-associated environments and the difficulties of studying them. We advocate for an environmental DNA sequencing-based approach to determine the microbial communities of oil sands associated environments, and the importance of studying the heterotrophic components of these environments to gain a full understanding of how these environments operate and thus how they can be integrated with the natural watersheds of the region.


In situ extractive fermentation of acetone and butanol.
The productivity of the acetone-butanol fermentation was increased by continuously removing acetone and butanol from the fermentation broth during fed-batch culture. Whole broth containing viable cells of Clostridium acetobutylicum was cycled to a Karr reciprocating plate extraction column in which acetone and butanol were extracted into oleyl alcohol flowing counter-currently through the column. By continuously removing these toxic metabolites from the broth, end product inhibition was reduced, and a concentrated feed solution containing 300 g/L glucose was fermented at an overall butanol productivity of 1.0 g/L h, 70% higher than the productivity of normal batch fermentation. The continuous extraction process provides flexible operation and lends itself to process scale-up.


Adrenal medulla autografts in Parkinson's disease: a proposed mechanism of action.
Concepts emerging from experimental manipulations of neurobiological systems in vivo and in vitro may provide explanations for some clinical observations following adrenal medulla autografting in patients with Parkinson's disease. These concepts are reviewed, and a proposed mechanism of action of adrenal autografts in Parkinson's disease is advanced.


Multi-omic approaches for characterization of hepatocellular carcinoma.
Multi-omic approaches offer the opportunity to characterize complex diseases such as cancer at various molecular levels. In this paper, we present transcriptomic, proteomic/glycoproteomic, glycomic, and metabolomic (TPGM) data we acquired by analysis of liver tissues from hepatocellular carcinoma (HCC) cases and patients with liver cirrhosis. We evaluated changes in the levels of transcripts, proteins, glycans, and metabolites between tumor and cirrhotic tissues by statistical methods. We demonstrated the potential of multi-omic approaches and network analysis to investigate the interactions among these biomolecules in the progression of liver cirrhosis to HCC. Also, we showed the significance of multi-omic approaches to identify pathways altered in HCC.


Positive biochemical effects of a bioartificial liver support system (BALSS) in a porcine fulminant hepatic failure (FHF) model.
This study describes biochemical changes in the plasma and blood of pigs with devascularised livers treated in a bioartificial liver support system (BALSS). Porcine hepatic cells were incubated with collagen-coated dextran microspheres (CDM) for 3 hours and the medium tested to determine cellular metabolic activity. Incubation continued for a further 18 hours during which the hepatic cells attach to the CDM. The CDM-attached cells were inoculated into a hollow fibre bioreactor which was part of an extracorporeal support system. Hepatic cell content of the bioreactor was 6 x 10(9) cells. The system was tested in a controlled trial in pigs prepared in a surgical model of fulminant hepatic failure (FHF). When plasma from FHF pigs was circulated through the device containing hepatic cells, there was significantly less increase in the accumulation of ammonia and most amino acids, together with a decrease in plasma lactate and of one amino acid, compared to control experiments when hepatic cells were excluded. We conclude that primary porcine hepatocytes can contribute beneficial metabolic function in a BALSS.


Structure Elucidation of 2D Polymer Monolayers Based on Crystallization Estimates Derived from Tip-Enhanced Raman Spectroscopy (TERS) Polymerization Conversion Data.
Structural elucidation of 2D polymer monolayers proving long-range order is a challenge that limits the pace in which this recent field of polymer chemistry and of synthetic 2D materials develops. To overcome this bottleneck, we here present a method in which tip-enhanced Raman spectroscopy is combined with a random growth crystallization model to obtain global features from local spectroscopic information. Concretely, we prove the nature and determine the conversion number X of the cross-links for two new 2D homopolymers and one (of three) new 2D copolymers. Assuming random and in-plane growth, our model results in crystallinity degrees of 93.1% to 99.7% and mean radii of defect-free crystalline areas of 3-15 nm for conversion numbers of 84% < X < 98%. Thus, we provide strong evidence for the synthetic monolayer 2D materials presented that they qualify as 2D polymers and are therefore perfectly suited for in-depth studies both in a more fundamental direction as well as toward application. This example shows how our method can affect current research on covalent sheets.


Prevalence of Oral Health Status among the General Population in Kallakurichi District, Tamil Nadu, India- A Cross-Sectional Study.
The aim of this study is to analyze the prevalence of oral health status among the general population in Kallakurichi district, Tamil Nadu, India. A descriptive cross-sectional study was conducted among the general public in the Kallakurichi district. A total number of 176 samples were selected and equally divided among urban (88 samples) and rural areas (88 samples). The samples were obtained from various parts of urban and rural areas in the Kallakurichi district based on the multistage random sampling method. The data regarding oral health status was recorded using the World Health Organization (WHO) Proformas 2013 and 1997. The collected data were tabulated and analyzed using the Chi-square test. The prevalence of dental caries (74.1%) was found to be the highest in the Kallakurichi district, followed by malocclusion (71.7%) and periodontal diseases (66.7%). A significant result was found in dental caries, dental fluorosis, dental trauma, and dental erosion between the index age groups. The government of Tamil Nadu should take proper preventive measures and also provide oral health knowledge and awareness among the public to overcome these dental problems.


The utility of multiple mini-interviews: experience of a medical school.
This paper aims to introduce the design of multiple mini-interviews (MMIs) as a tool to assess medical school applicants' attributes in alignment with the school's educational goals and to evaluate its utility. In this MMI, candidates rotated through six stations (10 minutes per station), in which specific interview topics were drawn by mapping the school's educational goals with the core competencies for entering medical students. We conducted post-MMI surveys of all of the interviewers and candidates to investigate their experiences of MMIs. The G-coefficient and interclass correlation were analyzed to investigate the reliability of this test. Additionally, the candidates' MMI scores were compared across different backgrounds and a univariate analysis was used to estimate correlations between their MMI scores and prior academic achievements. A total of 164 candidates (a 98.8% response rate) and 19 interviewers (a 100% response rate) completed the surveys in the years 2014 and 2015. Both candidates and assessors showed positive responses to MMIs. The G-coefficient of MMI scores was 0.88 and the interclass correlation coefficients ranged from 0.58 to 0.75. The participants' total MMI scores did not differ across genders or undergraduate backgrounds and were not associated with age, undergraduate graduate point averages, nor the Korean medical school admission test (Medical Education Eligibility Test) scores. Our study illustrates the utility of MMIs that utilize the institution's educational goals to identify attributes to be pursued in the admission interviews in alignment with the institution's core values. Future research is warranted of the predictive validity of this MMI.


Automatic pavement texture recognition using lightweight few-shot learning.
Texture is a crucial characteristic of roads, closely related to their performance. The recognition of pavement texture is of great significance for road maintenance professionals to detect potential safety hazards and carry out necessary countermeasures. Although deep learning models have been applied for recognition, the scarcity of data has always been a limitation. To address this issue, this paper proposes a few-shot learning model based on the Siamese network for pavement texture recognition with a limited dataset. The model achieved 89.8% accuracy in a four-way five-shot task classifying the pavement textures of dense asphalt concrete, micro surface, open-graded friction course and stone matrix asphalt. To align with engineering practice, global average pooling (GAP) and one-dimensional convolution are implemented, creating lightweight models that save storage and training time. Comparative experiments show that the lightweight model with GAP implemented on dense layers and one-dimensional convolution on convolutional layers reduced storage volume by 94% and training time by 99%, despite a 2.9% decrease in classification accuracy. Moreover, the model with only GAP implemented on dense layers achieved the highest accuracy at 93.5%, while reducing storage volume and training time by 83% and 6%, respectively. This article is part of the theme issue 'Artificial intelligence in failure analysis of transportation infrastructure and materials'.


Analysis of the effects of aberrations on coherent polarization beam combining of fiber laser beams.
In this paper, the influence of aberrations on coherent polarization beam combining (CPBC) of fiber laser beams is analyzed in detail for the first time to our knowledge. The expression of the coherently polarization combined output power is obtained, which contains the geometry and nongeometry factors of the CPBC system. The geometry and nongeometry aberrations are numerically studied to investigate their effects on the combining efficiency. It is found that to ensure the combining efficiency of a CPBC unit (we studied) to be more than 90%, the overlap error (the beams in the polarization beam combiner cannot be superposed entirely) should be controlled to be less than 0.45, the tilt error should be less than 2π/15 rad, and the RMS value of the phase error should be limited to be within λ/10. The generalized methodology that we present offers a good reference for investigating the CPBC system in an extensive way.


[Shock wave lithotripsy for ureteral stones--single institute experience in 661 consecutive cases].
Optimal treatment for ureteral stones is still controversial. The main retreatment options include ureteroscopy and shock wave lithotripsy (ESWL). The study aimed to assess the efficacy of ESWL using the unmodified HM3 lithotripter (Dornier Medical Systems) to achieve stone-free status in patients with ureteral calculi, regardless of stone size and location along the ureter. We retrospectively reviewed the charts and radiology studies of all patients who had ESWL for ureteral stones. Following ESWL with the HM3 lithotripter, patients had imaging examinations performed after 1 and 3 months, and thereafter, according to the residue status of the stones. During the years 1998-2003, 661 patients underwent ESWL for ureteral stones. The mean age was 51 years (range: 4-85 years) and the average stone size was 8 x 10 mm (range: 3-30 mm). Forty percent of the patients had upper ureteral calculi, 17% mid and 43% lower ureteral stone. Overall stone-free status was 93.6%. According to stone location, the success rate for upper ureteral calculi was 93.6%, and 93.6% and 95.5% for mid and lower ureteral stones. Complications were recorded in 28 (4.2%) patients, 20 had acute urinary tract infection treated with i.v. antibiotics, and 8 had renal colic treated conservatively. Our data shows that ESWL using HM3 lithotripter for ureteral stones at any level and size has a high success rate with minimal morbidity. ESWL using the HM3 lithotripter is our preferred treatment of choice for ureteral calculi.