Impact of COVID-19 and lockdown on mental health of children and adolescents: A narrative review with recommendations.
COVID-19 pandemic and lockdown has brought about a sense of fear and anxiety around the globe. This phenomenon has led to short term as well as long term psychosocial and mental health implications for children and adolescents. The quality and magnitude of impact on minors is determined by many vulnerability factors like developmental age, educational status, pre-existing mental health condition, being economically underprivileged or being quarantined due to infection or fear of infection. This paper is aimed at narratively reviewing various articles related to mental-health aspects of children and adolescents impacted by COVID-19 pandemic and enforcement of nationwide or regional lockdowns to prevent further spread of infection. We conducted a review and collected articles and advisories on mental health aspects of children and adolescents during the COVID-19 pandemic. We selected articles and thematically organized them. We put up their major findings under the thematic areas of impact on young children, school and college going students, children and adolescents with mental health challenges, economically underprivileged children, impact due to quarantine and separation from parents and the advisories of international organizations. We have also provided recommendations to the above. There is a pressing need for planning longitudinal and developmental studies, and implementing evidence based elaborative plan of action to cater to the psycho social and mental health needs of the vulnerable children and adolescents during pandemic as well as post pandemic. There is a need to ameliorate children and adolescents' access to mental health support services geared towards providing measures for developing healthy coping mechanisms during the current crisis. For this innovative child and adolescent mental health policies policies with direct and digital collaborative networks of psychiatrists, psychologists, paediatricians, and community volunteers are deemed necessary.


Eighteen-year-old man with autism, obsessive compulsive disorder and a SHANK2 variant presents with severe anorexia that responds to high-dose fluoxetine.
The SHANK2 gene codes for a protein involved in organising the postsynaptic density and disruptions have been associated with autism spectrum disorders (ASDs). ASDs are frequently comorbid with intellectual disability and anxiety disorders and emerging evidence suggests potentially common aetiologies. Here, we report the case of an 18-year-old man with ASD who presented with severe anorexia due to fear of food contamination, food avoidance and stereotypies attributable to underlying obsessive compulsive disorder (OCD). The patient was found to be heterozygous for c.2518C>T (p.Pro840Ser), a likely damaging coding variant in the proline rich region of SHANK2 Interestingly, the patient's disordered eating behaviour began to improve only after high-dose fluoxetine was initiated to target OCD symptoms. Overall, this case highlights the utility of molecular genetic testing in clinical psychiatry and provides an example of how genetic information can inform clinicians in the treatment of complex neuropsychiatric syndromes.


Mechanical properties of grafold: a demonstration of strengthened graphene.
Morphological patterns and structural features play crucial roles in the physical properties of functional materials. In this paper, the mechanical properties of grafold, an architecture of folded graphene nanoribbon, are investigated via molecular dynamics simulations and intriguing features are discovered. In contrast to graphene, grafold is found to develop large deformations upon both tensile and compressive loading along the longitudinal direction. The tensile deformation is plastic, whereas the compressive deformation is elastic and reversible within the strain range investigated. The calculated Young's modulus, tensile strength, and fracture strain are comparable to those of graphene, while the compressive strength and strain are much higher than those of graphene. The length, width, and folding number of grafold have distinctive impacts on the mechanical performance. These unique behaviors render grafold a promising material for advanced mechanical applications.


Gambling Patterns and Problems of Gamblers on Licensed and Unlicensed Sites in France.
In 2010 France enacted a law to regulate supply and consumption of online gambling. Its primary aim was to protect citizens from gambling-related harm. This study aims to assess differences in gambling patterns and related harm between online gamblers who use licensed versus unlicensed sites. Participants (N = 3860) completed a self-administered online survey on gambling practices. Pairwise logistic regressions examined the association between the legal statuses of gambling sites people patronized and demographic variables and gambling types. Multivariate logistic regression models explored associations between gambling patterns and related problems according to the legal status of sites people have gambled on. Overall, 53.7 % of online gamblers report gambling exclusively on licensed sites. Those who bet on regulated activities on unlicensed sites, versus licensed sites, are more likely to be female, younger, less educated, inactive in the labor market and are more likely to perceive their financial situation to be difficult. Gambling on unlicensed sites is associated with more intense gambling patterns and more gambling-related problems compared to licensed sites. Findings demonstrate that gambling activities carried out on state licensed sites are associated with less overall harm to gamblers. Implications of these findings on future policy are discussed and prospective research directions are outlined.


Dysmagnesemia in Hospitalized Patients: Prevalence and Prognostic Importance.
To examine the prevalence of serum magnesium (Mg) alterations and outcomes in hospitalized patients. All admissions to Mayo Clinic in Rochester, Minnesota, from January 1, 2009, through December 31, 2013 (288,120 patients), were screened. Admission Mg from each unique patient and relevant clinical data were extracted from the institutional electronic database. After excluding patients aged less than 18 years, those without Mg measurement, and readmission episodes, a total of 65,974 patients were studied. Magnesium levels of 2.1 mg/dL or higher were found in 20,777 patients (31.5%), and levels less than 1.7 mg/dL were noted in 13,320 (20.2%). Hypomagnesemia was common in patients with hematologic/oncological disorders, and hypermagnesemia was common in those with cardiovascular disease. The lowest hospital mortality, assessed by restricted cubic spline and percentage death, occurred in patients with Mg levels between 1.7 and 1.89 mg/dL. An Mg level of less than 1.7 mg/dL was independently associated with an increased risk of hospital mortality after adjusting for all variables except the admission diagnosis; risk for longer hospital stay and being discharged to a care facility were increased in the fully adjusted model. An elevated Mg level of 2.3 mg/dL or higher was a predictor for all adverse outcomes. The magnitude of Mg elevations in patients with levels of 2.3 mg/dL or higher (N=7908) was associated with worse hospital mortality in a dose-response manner. In patients with cardiovascular diseases, Mg levels of 1.5 to 1.69 mg/dL and 2.3 mg/dL or higher both independently predicted poor outcomes including hospital mortality. Dysmagnesemia in hospitalized patients is common, with hypermagnesemia being most prevalent. Compared with hypomagnesemia, hypermagnesemia is a stronger predictor for poor outcomes. Magnesium supplementation for patients without Mg deficiency should be avoided in the absence of randomized controlled trials documenting a benefit.


Association between transcriptional activity, local chromatin structure, and the efficiencies of both subpathways of nucleotide excision repair of melphalan adducts.
The repair of melphalan-induced N-alkylpurine monoadducts and interstrand cross-links was examined in different repair backgrounds, focusing on four genes (beta-actin, p53, N-ras, and delta-globin) with dissimilar transcription activities. Adducts were found to be substrates for both global genome repair (GGR) and transcription-coupled repair (TCR), with TCR being less efficient than GGR. In nucleotide excision repair-deficient cells, adducts accumulated to similar levels in all four genes. The repair efficiency in different gene loci varied in a qualitatively and quantitatively similar way in both GGR-deficient and TCR-deficient backgrounds and correlated with transcriptional activity and local chromatin condensation. No strand-specific repair was found in GGR(+)/TCR(+) cells, implying that GGR dominated. Adducts were lost over two sharply demarcated phases: a rapid phase resulting in the removal within 1 hour of up to approximately 80% of the adducts, and a subsequent phase with t(1/2) approximately 36 to 48 hours. Following pretreatment of cells with alpha-amanitin, the rate of transcription, the state of chromatin condensation, and the repair efficiencies (both TCR and GGR) of the transcribed beta-actin, p53, and N-ras genes became similar to those of the nontranscribed delta-globin gene. In conclusion, a continuous, parallel variation of the state of transcription and local chromatin condensation, on one hand, and the rates of both GGR and TCR, on the other hand, have been shown.


Comparative efficacy of materials used in patients undergoing pulpotomy or direct pulp capping in carious teeth: A systematic review and meta-analysis.
Different materials have been used for capping the pulp after exposure during caries removal in permanent teeth. The purpose of this study was to collate and analyze all pertinent evidence from randomized controlled trials (RCTs) on different materials used in patients undergoing pulpotomy or direct pulp capping in carious teeth. Trials comparing two or more capping agents used for direct pulp capping (DPC) or pulpotomy were considered eligible. An electronic search of four databases and two clinical trial registries was carried out up to February 28, 2021 using a search strategy properly adapted to the PICO framework. Screening, data extraction, and risk of bias (RoB) assessment of primary studies were performed in duplicate and independently. The primary outcome was clinical and radiological success; secondary outcomes included continued root formation, tooth discoloration, and dentin bridge formation. 21 RCTs were included in the study. The RoB assessment indicated a moderate risk among the studies. Due to significant clinical and statistical heterogeneity among the studies, performing network meta-analysis (NMA) was not possible. An ad hoc subgroup analysis revealed strong evidence of a higher success of DPC with Mineral Trioxide Aggregate (MTA) compared to calcium hydroxide (CH) (odds ratio [OR] = 3.10, 95% confidence interval [CI]: 1.66-5.79). MTA performed better than CH in pulp capping (both DPC and pulpotomy) of mature compared to immature teeth (OR = 3.34, 95% CI: 1.81-6.17). The GRADE assessment revealed moderate strength of evidence for DPC and mature teeth, and low to very low strength of evidence for the remaining subgroups. Considerable clinical and statistical heterogeneity among the trials did not allow NMA. The ad hoc subgroup analysis indicated that the clinical and radiographic success of MTA was higher than that of CH but only in mature teeth and DPC cases where the strength of evidence was moderate. PROSPERO Registration: number CRD42020127239.


cGAS-STING Pathway Activation during Trypanosoma cruzi Infection Leads to Tissue-Dependent Parasite Control.
Host cell invasion by Trypanosoma cruzi is a markedly silent process, with limited host transcriptional changes indicative of innate immune recognition, except for a modest type I IFN (IFN-I) response. In this study, we show that T. cruzi-induced IFN-β production was nearly abolished in primary murine cGAS-/- or stimulator of IFN genes (STING)-deficient (STINGGt) macrophages and fibroblasts. T. cruzi infection did not impact the ability of IFN-regulatory factor reporter macrophages to respond to classical cGAS-STING agonists, indicating that the limited IFN-β induction is not due to active parasite suppression. cGAS-/-, STINGGt, and IFN-α/β receptor-/- (IFNAR-/-) macrophages infected with T. cruzi yielded significantly higher numbers of amastigotes compared with wild-type macrophages; however, the impact of the STING pathway during infection in vivo is more complex. Despite an initial increase in parasite growth, STINGGt and IFNAR-/- mice ultimately had lower parasite burden in footpads as compared with wild-type mice, demonstrating a role for IFN-I expression in potentiating parasite growth at the infection site. STING pathway activation had little impact on parasite levels in the skeletal muscle; however, in the heart, cGAS-/- and STINGGt mice, but not IFNAR-/- mice, accumulated higher acute parasite loads, suggesting a protective role of STING sensing of T. cruzi in this organ that was independent of IFN-I. Together, these results demonstrate that host cGAS-STING senses T. cruzi infection, enhancing parasite growth at the site of entry, and contributes to acute-phase parasite restriction in the heart, a major site of tissue damage in chronic T. cruzi infection.


Everett Kinsey Lecture. Keratocyte apoptosis in refractive surgery.
The purpose of this paper is to review the relevance of keratocyte programmed cell death (apoptosis) in response to epithelial injury to corneal wound healing following refractive surgery and the pathogenesis of corneal diseases such as keratoconus. The TUNEL assay (to detect DNA fragmentation in situ) DNA laddering assay, and transmission electron microscopy have been used to detect apoptosis in human and animal corneas and cultured corneal cells. Molecular and cell biologic techniques have been used to study the cytokine-receptor systems that are involved in modulating apoptosis in the cornea. Keratocyte apoptosis, mediated through the release of cytokines such as soluble Fas ligand and interleukin-1 from the injured epithelium, occurs following refractive surgical procedures like photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK). Keratocytes that die in the anterior stroma following PRK or along the lamellar cut following LASIK are replenished in 2 to 4 days by proliferation and migration. The replenishing cells are activated myofibroblastic keratocytes that produce collagen, hyaluronic acid, growth factors modulating epithelial healing, and other components of the wound healing response. Keratocyte apoptosis can be inhibited by transepithelial PRK (probably by photodisruption of the apoptotic cytokines in the epithelium) or pharmacologic agents. Keratocyte apoptosis may be an initiator of the wound healing response in the cornea. Control of this response has the potential to regulate wound healing in the cornea in response to PRK or LASIK. Recent evidence suggests that keratocyte apoptosis mediated by chronic epithelial injury could have a role in the pathogenesis of keratoconus.


Small-scale analysis of O-linked oligosaccharides from glycoproteins and mucins separated by gel electrophoresis.
A technique with subpicomolar sensitivity was developed for analyzing O-linked oligosaccharides released from glycoproteins separated by gel electrophoresis. The protocol involves gel electrophoresis, electroblotting to poly-(vinylidene fluoride) membrane, reductive beta-elimination, and analysis of released oligosaccharides by liquid chromatography coupled to negative ion electrospray mass spectrometry. It was also found that N-linked oligosaccharides could be recovered under the same conditions, found both as free oligosaccharides and as distinct glycopeptides created from reductive cleavage of the protein backbone, giving some information on site-specific glycosylation. The method was used to demonstrate that the difference between human alpha-2HS-glycoprotein isoforms separated by 2D-gel electrophoresis was partially due to sialylation of both O-linked and N-linked oligosaccharides. It was also shown that both acidic and neutral oligosaccharides could be recovered and analyzed simultaneously from high molecular mass (200,000-5,000,000 Da) highly glycosylated mucin glycoproteins collected from small intestine and saliva and separated by sodium dodecyl sulfate-agarose/polyacrylamide composite gels. Mass spectrometric data not only gave information about the mass distribution of the heterogeneous mixtures of oligosaccharides from [M - xH](x-) ions but also gave information about the isomeric heterogeneity of the oligosaccharides from their resolution by porous graphitized carbon chromatography. Tandem mass spectrometry was explored as a technique for distinguishing between oligosaccharide isomers with different sequences and also between oligosaccharides with the same sequence but with different linkage configurations.


Caveat anicula! Beware of quiet little old ladies: demographic features, pharmacotherapy, readmissions and survival in a 10-year cohort of patients with heart failure and preserved systolic function.
To determine whether heart failure with preserved systolic function (HFPSF) has different natural history from left ventricular systolic dysfunction (LVSD). A retrospective analysis of 10 years of data (for patients admitted between 1 July 1994 and 30 June 2004, and with a study census date of 30 June 2005) routinely collected as part of clinical practice in a large tertiary referral hospital. Sociodemographic characteristics, diagnostic features, comorbid conditions, pharmacotherapies, readmission rates and survival. Of the 2961 patients admitted with chronic heart failure, 753 had echocardiograms available for this analysis. Of these, 189 (25%) had normal left ventricular size and systolic function. In comparison to patients with LVSD, those with HFPSF were more often female (62.4% v 38.5%; P = 0.001), had less social support, and were more likely to live in nursing homes (17.9% v 7.6%; P < 0.001), and had a greater prevalence of renal impairment (86.7% v 6.2%; P = 0.004), anaemia (34.3% v 6.3%; P = 0.013) and atrial fibrillation (51.3% v 47.1%; P = 0.008), but significantly less ischaemic heart disease (53.4% v 81.2%; P = 0.001). Patients with HFPSF were less likely to be prescribed an angiotensin-converting enzyme inhibitor (61.9% v 72.5%; P = 0.008); carvedilol was used more frequently in LVSD (1.5% v 8.8%; P < 0.001). Readmission rates were higher in the HFPSF group (median, 2 v 1.5 admissions; P = 0.032), particularly for malignancy (4.2% v 1.8%; P < 0.001) and anaemia (3.9% v 2.3%; P < 0.001). Both groups had the same poor survival rate (P = 0.912). Patients with HFPSF were predominantly older women with less social support and higher readmission rates for associated comorbid illnesses. We therefore propose that reduced survival in HFPSF may relate more to comorbid conditions than suboptimal cardiac management.


Regulation of a specific circadian clock output pathway by lark, a putative RNA-binding protein with repressor activity.
An endogenous clock within the Drosophila brain regulates circadian rhythms in adult eclosion and locomotor activity. Although molecular elements of the Drosophila circadian clock have been well characterized, little is known about the clock output pathways that mediate the control of rhythmic events. Previous genetic analysis indicates that a gene known as lark encodes an element of the clock output pathway regulating adult eclosion. We now present evidence that lark encodes a novel member of the RNA recognition motif (RRM) class of RNA-binding proteins. Similar to other members of this protein superfamily, lark contains two copies of a bipartite consensus RNA-binding motif. Unlike any other RRM family member, however, lark protein also contains a distinct class of nucleic acid binding motif, a retroviral-type zinc finger, that is present in the nucleocapsid protein of retroviruses and in several eukaryotic proteins. In contrast to identified clock elements, lark mRNA does not exhibit diurnal fluctuations in abundance in late pupae or in adult heads. Thus rhythmic transcription of the gene does not contribute to the temporal regulation of eclosion by lark protein. Gene dosage experiments show that decreased or increased lark product, respectively, leads to an early or late eclosion phenotype, indicating that the protein negatively regulates the eclosion process. It is postulated that lark is required for the posttranscriptional repression of genes encoding other elements of this clock output pathway.


Targeted Inhibition of Anti-Inflammatory Regulator Nrf2 Results in Breast Cancer Retardation In Vitro and In Vivo.
Nuclear factor erythroid-2 related factor-2 (Nrf2) is an oxidative stress-response transcriptional activator that promotes carcinogenesis through metabolic reprogramming, tumor promoting inflammation, and therapeutic resistance. However, the extension of Nrf2 expression and its involvement in regulation of breast cancer (BC) responses to chemotherapy remain largely unclear. This study determined the expression of Nrf2 in BC tissues (n = 46) and cell lines (MDA-MB-453, MCF-7, MDA-MB-231, MDA-MB-468) with diverse phenotypes. Immunohistochemical (IHC)analysis indicated lower Nrf2 expression in normal breast tissues, compared to BC samples, although the difference was not found to be significant. However, pharmacological inhibition and siRNA-induced downregulation of Nrf2 were marked by decreased activity of NADPH quinone oxidoreductase 1 (NQO1), a direct target of Nrf2. Silenced or inhibited Nrf2 signaling resulted in reduced BC proliferation and migration, cell cycle arrest, activation of apoptosis, and sensitization of BC cells to cisplatin in vitro. Ehrlich Ascites Carcinoma (EAC) cells demonstrated elevated levels of Nrf2 and were further tested in experimental mouse models in vivo. Intraperitoneal administration of pharmacological Nrf2 inhibitor brusatol slowed tumor cell growth. Brusatol increased lymphocyte trafficking towards engrafted tumor tissue in vivo, suggesting activation of anti-cancer effects in tumor microenvironment. Further large-scale BC testing is needed to confirm Nrf2 marker and therapeutic capacities for chemo sensitization in drug resistant and advanced tumors.


Potential of human umbilical cord blood mesenchymal stem cells to heal damaged corneal endothelium.
To test the feasibility of altering the phenotype of umbilical cord blood mesenchymal stem cells (UCB MSCs) toward that of human corneal endothelial cells (HCEC) and to determine whether UCB MSCs can "home" to sites of corneal endothelial cell injury using an ex vivo corneal wound model. RNA was isolated and purified from UCB MSCs and HCECs. Baseline information regarding the relative gene expression of UCB MSCs and HCEC was obtained by microarray analysis. Quantitative real-time PCR (q-PCR) verified the microarray findings for a subset of genes. The ability of different culture media to direct UCB MSCs toward a more HCEC-like phenotype was tested in both tissue culture and ex vivo corneal endothelial wound models using three different media: MSC basal medium (MSCBM), a basal medium used to culture lens epithelial cells (LECBM), or lens epithelial cell-conditioned medium (LECCM). Morphology of the MSCs was observed by phase-contrast microscopy or by light microscopic observation of crystal violet-stained cells. Immunolocalization of the junction-associated proteins, zonula occludins-1 (ZO1) and N-cadherin, was visualized by fluorescence confocal microscopy. Formation of cell-cell junctions was tested by treatment with the calcium chelator, EGTA. A second microarray analysis compared gene expression between UCB MSCs grown in LECBM and LECCM to identify changes induced by the lens epithelial cell-conditioned culture medium. The ability of UCB MSCs to "home" to areas of endothelial injury was determined using ZO1 immunolocalization patterns in ex vivo corneal endothelial wounds. Baseline microarray analysis provided information regarding relative gene expression in UCB MSCs and HCECs. MSCs attached to damaged, but not intact, corneal endothelium in ex vivo corneal wounds. The morphology of MSCs was consistently altered when cells were grown in the presence of LECCM. In tissue culture and in ex vivo corneal wounds, UCB MSC treated with LECCM were elongated and formed parallel sheets of closely apposed cells. In both tissue culture and ex vivo corneal endothelial wounds, ZO1 and N-cadherin localized mainly to the cytoplasm of UCB MSCs in the presence of MSCBM. However, both proteins localized to cell borders when UCB MSCs were grown in either LECBM or LECCM. This localization was lost when extracellular calcium levels were reduced by treatment with EGTA. A second microarray analysis showed that, when UCB MSCs were grown in LECCM instead of LECBM, the relative expression of a subset of genes markedly differed, suggestive of a more HCEC-like phenotype. Results indicate that UCB MSCs are able to "home" to areas of injured corneal endothelium and that the phenotype of UCB MSCs can be altered toward that of HCEC-like cells. Further study is needed to identify the specific microenvironmental conditions that would permit tissue engineering of UCB MSCs to replace damaged or diseased corneal endothelium.


Targeting SARS-CoV-2 spike protein by stapled hACE2 peptides.
SARS-CoV-2 Spike protein RBD interacts with the hACE2 receptor to initiate cell entry and infection. We set out to develop lactam-based i,i + 4 stapled hACE2 peptides targeting SARS-CoV-2. In vitro screening demonstrates the inhibition of the Spike protein RBD-hACE2 complex formation by the hACE221-55A36K-F40E stapled peptide (IC50: 3.6 μM, Kd: 2.1 μM), suggesting that hACE2 peptidomimetics could form the basis for the development of anti-COVID-19 therapeutics.


Intranasal Delivery of Nanotherapeutics/ Nanobiotherapeutics for the Treatment of Alzheimer's Disease: A Proficient Approach.
Therapeutics and biotherapeutics-based fabrication of nanoparticles has fascinated scientists since the past two decades and exciting challenges have been surmounted. Particular interest has been paid to the exploitation of functionalized nanocarriers in the treatment of Alzheimer's disease (AD) using nasal route. Development of various material-based nanocarriers is a common approach to obtain advanced drug delivery systems possessing the ability to follow intranasal (IN) route for brain targeting, which would ultimately ameliorate the effect of AD. This review highlights the various pathological theories for AD along with their controversies. This work intends to provide a thorough, up-to-date, and holistic discussion on various pathways for nose-to-brain delivery and different formulation factors impacting on nasal absorption. The various material properties and their engineered nanocarriers as a smart delivery system, including synergistic effect of therapeutic/biotherapeutic agent in IN delivery as well as in AD therapy have been discussed. This review also emphasizes toxicity, especially neurotoxicity concerns pertaining to drug delivery systems.


An analysis of the process of human immunodeficiency virus sexual risk behavior change.
Few studies have tried to identify the process of risk behavior change. In this paper, we present a method for the analysis of the process of risk behavior change; the methodology involves using time series data to form transition probability matrices. We apply the method to human immunodeficiency virus (HIV) sexual risk behavioral data from a cohort of gay men in Amsterdam. We determine the process of risk behavior change in this cohort, and we demonstrate that it is not possible to deduce the process simply from an examination of the static pattern. Our results imply that the risk behavior change that is observed in this cohort may be viewed as a homogeneous one-step Markovian process. This process of risk behavior change has implications for the long-term prediction of HIV seroconversion rates and for the design and evaluation of HIV behavioral intervention studies and vaccine trials. Our results also have implications for the interpretation of relapse behavior.


USPs in Pancreatic Ductal Adenocarcinoma: A Comprehensive Bioinformatic Analysis of Expression, Prognostic Significance, and Immune Infiltration.
Pancreatic ductal adenocarcinoma (PDAC), as an intractable malignancy, still causes an extremely high mortality worldwide. The ubiquitin-specific protease (USP) family constitutes the major part of deubiquitinating enzymes (DUBs) which has been reported to be involved in initiation and progression of various malignancies via the function of deubiquitination. However, the biological function and clinical values of USPs in PDAC have not been comprehensively elucidated. In this study, Gene Expression Profiling Interactive Analysis (GEPIA), Gene Expression Omnibus (GEO) datasets, UALCAN database, and the Human Protein Atlas (HPA) online tool were used to analyze the expression level and the relationship between USP expression and clinicopathological features in PDAC. Survival module of HPA and Kaplan-Meier plotter (KMP) databases was recruited to explore the prognostic value of USPs. Tumor Immune Estimation Resource (TIMER) online tool and KMP databases were utilized to elucidate tumor immune infiltration and immune-related survival of USPs. CBioPortal online tool was used to identify the gene mutation level of USPs in PDAC. Both cBioPortal and LinkedOmics were used to confirm the potential biological functions of USPs in PDAC. Our study showed that USP10, USP14, USP18, USP32, USP33, and USP39 (termed as six-USPs) expressions were significantly elevated in tumor tissues. The high expression of the four USPs (USP10, USP14, USP18, and USP39) indicated a poor prognosis. A significant relationship was indicated between the expression of six-USPs and clinicopathological features. Also, the expression of six-USPs was related to promoter methylation level. Moreover, more than 40% genetic alterations and mutations were discovered in six-USPs. Furthermore, the six-USP expression was correlated with immune infiltration and immune-related prognosis. The functional analysis found that the six-USPs were involved in various biological processes and signaling pathways, such as nucleocytoplasmic transport, choline metabolism in cancer, cell cycle, ErbB signaling pathway, RIG-I-like receptor signaling pathway, TGF-β signaling pathway, and TNF signaling pathway. In conclusion, the results showed that six-USPs are potential prognostic biomarkers and can be recruited as possible therapeutic targets of PDAC.


Clinical features and outcomes in acute psychosis: A retrospective hospital-based study in rural patients of central India.
Acute and transient psychotic disorder (ATPD) is a distinct diagnostic category (F23) in ICD-10 which includes non-schizophrenic and non-affective psychoses following a transient course. The clinical features, diagnostic stability, and epidemiology of ATPD have not been adequately explored in the developing countries. The aim was to explore the socio-demographic and clinical characteristics of ATPD as well as examine the diagnostic stability and longitudinal revisions in the diagnosis of ATPD. An observational retrospective study based on 10-year OPD records of ATPD patients was conducted in a tertiary health care center after ethics committee approval. A total of 120 patient records were analyzed for socio-demographic data, clinical symptoms, mental status examination findings, diagnosis on the first visit, and subsequent revisions in the diagnosis. The mean age of ATPD patients was 31.8 (±11.73) years. Delusion was the most common psychiatric symptom in ATPD patients followed by abnormal speech, hallucinations, and disorganized behavior. Antecedent psychosocial stressors were found in 44.2% cases. More than half of ATPD patients (51%) followed up after initial symptom remission and were diagnosed with chronic mental illnesses (schizophrenia or bipolar affective disorder). The ATPD patients experiencing a stressor at the onset of illness were less likely to develop chronic mental illness compared to the ones who did not have antecedent stressors. Irrespective of the genetic and phenomenological distinctiveness of ATPD, which has led to its inclusion as a separate diagnostic category in ICD-10, ATPD is an unstable diagnosis.


Environmental Temperature Drastically Affects Flexural Fatigue Resistance of Nickel-titanium Rotary Files.
The aim of the present study was to analyze how a low environmental temperature can affect the fatigue life of instruments made by different types of heat-treated nickel-titanium alloys. The flexural cyclic fatigue of 40 new specimens for each of the following systems was tested for cyclic fatigue resistance: ProTaper Universal F2 (Dentsply Maillefer, Ballaigues, Switzerland), ProTaper Gold F2 (Dentsply Tulsa Dental Specialties, Tulsa, OK), Twisted Files SM2 (SybronEndo, Orange, CA), Mtwo #25.06 (VDW, Munich, Germany), and Vortex Blue #30.04 and #40.06 (Dentsply Tulsa Dental Specialties). Instruments were tested at 2 different environmental temperatures: 20°C (±2°C) for room temperature (RT) group and -20°C (±2°C) for the cooled environment (CE) group (n = 20). The number of cycles to failure (NCF) and the length of the fractured fragment (FL) were recorded. The means and standard deviations of NCF and FL were then calculated; NCF data were statistically analyzed using a paired t test between groups RT and CE for each instrument tested (P < .05), whereas FL data were analyzed using analysis of variance (P < .05). The mean NCF values measured were significantly higher for the CE groups than the RT groups in all the systems tested (P < .05). The increase in cyclic fatigue resistance varied from 274%-854%. No differences in FL were registered among the different groups (P < .05). A low environmental temperature determines a drastic increase in the flexural fatigue resistance of NiTi endodontic instruments manufactured with traditional alloy and different heat treatments.


Chloropolysporins A, B and C, novel glycopeptide antibiotics from Faenia interjecta sp. nov. III. Structure elucidation of chloropolysporins.
Structure elucidations of chloropolysporins A, B and C were achieved mainly by chemical degradation studies. These components possessed the same pseudoaglycone in common and their structures were closely related to that of beta-avoparcin. The structures of chloropolysporins differ from that of beta-avoparcin in the presence of vancomycinic acid moiety instead of monodechlorovancomycinic acid moiety and glucose, not ristosaminylglucose, in its side chain. Chloropolysporin C was identified as derhamnosylchloropolysporin B based on its 1H NMR and mass spectral analysis and degradation studies. Two minor components, chloropolysporins D and E, were identified as the epimers of each of chloropolysporins B and C, respectively, based on their Cotton effects and retention times on reverse phase HPLC.


The coherent motions of thermal active Brownian particles.
Active matter exhibits many intriguing non-equilibrium characteristics, for instance, without any attractive and aligned interactions, the active Brownian particle (ABP) system undergoing motility-induced phase separation forms a high-density phase with both structural ordering and dynamical coherence. Recently, the velocity correlation among the particles in this high-density phase was found in non-thermal overdamped ABP systems. However, it seemed to disappear if thermal noises were included, bringing some confusion about the generality of the consistency between structures and dynamics in ABPs. Here, we demonstrate that the thermal noises imposing a large random term on the instantaneous velocity of ABPs hinder the observation of the inherent correlation in the motions of ABPs. By averaging the instantaneous velocity (or equivalently, calculating the displacement), we show that the inherent motions of thermal-fluctuated ABPs are highly coherent. Whether there is thermal noise or not, the inherent collective motions of ABPs do exist, and the collective motion domains are consistent spatially with the ordered clusters of ABPs in the high-density phase. At the boundary of these ordered clusters, the active forces of the particles tend to point inward and compress to sustain these clusters, thus the particles in the clusters move coherently to form some vortex-like or aligned velocity domains.


A review of bioceramics and fibrin sealant.
This review focuses on bone substitute composites made by mixing ceramic biomaterials with fibrin sealants. Different biomaterials such as coral, bone-derived materials, bioactive glass ceramics, and synthetic calcium phosphate have been mixed with fibrin sealant, resulting in a combination of the biological properties of the two components. This type of association has not produced identical results in all studies. In the past for some, the addition of fibrin sealant to the biomaterial failed to produce any significant, positive effect on osteointegration, whereas others found a positive impact on bone colonization. Despite the negative biological effects reported previously, bioceramic-fibrin composites have been widely used in various types of bone surgery because they are easy to manipulate. In particular, the intra-operative preparation of these composites makes it possible to add bone growth factors or autologous osteoprogenitor cells prior to bone reconstruction. The bone growth factors and autologous osteoprogenitor cells associated with the bioceramic-fibrin composites should provide surgeons with tissue engineered grafts with enhanced osteointegrative properties. This review discusses both the advantages and disadvantages, as well as the future perspectives, of using bioceramic-fibrin composites in various clinical indications.


Epilogue: what we know about nonspeech oral motor exercises.
A great deal of information is available to help clinicians understand the principles of motor speech learning and control, and how to apply those principles to clinical practice. In addition, the results of many investigations have documented the differences between the motor movements for speech and nonspeech tasks. Finally, supporting evidence for using nonspeech tasks to improve speech is virtually nonexistent. All of that information, taken in concert, casts doubt on the use of nonspeech techniques for improving children's speaking skills. However, clinicians have available a variety of viable intervention techniques to help children improve speech productions. This article presents a summary of reasons not to use nonspeech remediation techniques along with suggestions clinicians should consider when choosing intervention procedures for children with speech sound errors.


Negative fitness consequences and transmission dynamics of a heritable fungal symbiont of a parasitic wasp.
Heritable bacterial symbionts are widespread in insects and can have many important effects on host ecology and fitness. Fungal symbionts are also important in shaping their hosts' behavior, interactions, and evolution, but they have been largely overlooked. Experimental tests to determine the relevance of fungal symbionts to their insect hosts are currently extremely rare, and to our knowledge, there have been no such tests for strictly predacious insects. We investigated the fitness consequences for a parasitic wasp (Comperia merceti) of an inherited fungal symbiont in the Saccharomycotina (Ascomycota) that was long presumed to be a mutualist. In comparisons of wasp lines with and without this symbiont, we found no evidence of mutualism. Instead, there were significant fitness costs to the wasps in the presence of the yeast; infected wasps attacked fewer hosts and had longer development times. We also examined the relative competitive abilities of the larval progeny of infected and uninfected mothers, as well as horizontal transmission of the fungal symbiont among larval wasps that shared a single host cockroach egg case. We found no difference in larval competitive ability when larvae whose infection status differed shared a single host. We did find high rates of horizontal transmission of the fungus, and we suggest that this transmission is likely responsible for the maintenance of this infection in wasp populations.


Peripheral levels of superoxide dismutase and glutathione peroxidase in youths in ultra-high risk for psychosis: a pilot study.
IntroductionOxidative stress has been documented in chronic schizophrenia and in the first episode of psychosis, but there are very little data on oxidative stress prior to the disease onset. This work aimed to compare serum levels of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in young individuals at ultra-high risk (UHR) of developing psychosis with a comparison healthy control group (HC). Thirteen UHR subjects and 29 age- and sex-matched healthy controls (HC) were enrolled in this study. Clinical assessment included the Comprehensive Assessment of At-Risk Mental States (CAARMS), the Semi-Structured Clinical Interview for DSM-IV Axis-I (SCID-I) or the Kiddie-SADS-Present and Lifetime Version (K-SADS-PL), and the Global Assessment of Functioning (GAF) scale. Activities of SOD and GPx were measured in serum by the spectrophotometric method using enzyme-linked immunosorbent assay kits. After adjusting for age and years of education, there was a significant lower activity of SOD and lower GPX activity in the UHR group compared to the healthy control group (rate ratio [RR]=0.330, 95% CI 0.187; 0.584, p<0.001 and RR=0.509, 95% CI 0.323; 0.803, p=0.004, respectively). There were also positive correlations between GAF functioning scores and GPx and SOD activities. Our results suggest that oxidative imbalances could be present prior to the onset of full-blown psychosis, including in at-risk stages. Future studies should replicate and expand these results.


Breakthrough and Episodic Cancer Pain from a Palliative Care Perspective.
Cancer pain intensity (PI) fluctuates, but the relationship between pain flares and background pain with respect to pain management is not settled. We studied how flare and background PIs corresponded with treatment results for background cancer pain. Patients admitted to an acute palliative care unit with average and/or worst PI ≥ 1 on the 11-point numeric rating scale were included. Average and worst PI at admission and average PI at discharge were collected. We examined how the difference and ratio between worst and average PI and average PI at admission, were associated with average PI development during hospitalization. Positive differences between worst and average PI at admission were defined as pain flares. Ninety out of 131 patients had pain flares. The reduction in average PI for patients with flares was 0.9 and for those without, 1.9 (p = 0.02). Patients with large worst minus average PI differences reported the least improvement, as did those with large worst/average PI ratios. Patients with pain flares and average PI ≤ 4 at admission had unchanged average PI during hospitalization, while those with pain flares and average PI > 4 experienced pain reduction (2.1, p < 0.001). Large pain flares, in absolute values and compared to background PI, were associated with inferior pain relief.


[Isolation of steroid-binding proteins on new affinity adsorbents].
Steroid-binding proteins of human blood are extracted and investigated on corticosteroid-hydrazide-oxypropyl-adsorbents by the affinity chromatography. The role of structural changes in the matrix-spacer-ligand system for different types of adsorbents is studied as well as a dependence of sorption on pH and salt environment. A dependence of the protein sorption on the isolated hydrazide groups is revealed. It is shown that hydrocortisone displays the highest binding activity to the protein pool in the affinity electroimmunoassay while the substance S-Reichstein and its 16-alpha-methyl analog--the least one.


The Johns Hopkins Venous Thromboembolism Collaborative: Multidisciplinary team approach to achieve perfect prophylaxis.
Venous thromboembolism (VTE) is an important cause of preventable harm in hospitalized patients. The critical steps in delivery of optimal VTE prevention care include (1) assessment of VTE and bleeding risk for each patient, (2) prescription of risk-appropriate VTE prophylaxis, (3) administration of risk-appropriate VTE prophylaxis in a patient-centered manner, and (4) continuously monitoring outcomes to identify new opportunities for learning and performance improvement. To ensure that every hospitalized patient receives VTE prophylaxis consistent with their individual risk level and personal care preferences, we organized a multidisciplinary task force, the Johns Hopkins VTE Collaborative. To achieve the goal of perfect prophylaxis for every patient, we developed evidence-based, specialty-specific computerized clinical decision support VTE prophylaxis order sets that assist providers in ordering risk-appropriate VTE prevention. We developed novel strategies to improve provider VTE prevention ordering practices including face-to-face performance reviews, pay for performance, and provider VTE scorecards. When we discovered that prescription of risk-appropriate VTE prophylaxis does not ensure its administration, our multidisciplinary research team conducted in-depth surveys of patients, nurses, and physicians to design a multidisciplinary patient-centered educational intervention to eliminate missed doses of pharmacologic VTE prophylaxis that has been funded by the Patient Centered Outcomes Research Institute. We expect that the studies currently underway will bring us closer to the goal of perfect VTE prevention care for every patient. Our learning journey to eliminate harm from VTE can be applied to other types of harm. Journal of Hospital Medicine 2016;11:S8-S14. © 2016 Society of Hospital Medicine.


Negative pressure wound therapy of chronically infected wounds using 1% acetic Acid irrigation.
Negative-pressure wound therapy (NPWT) induces angiogenesis and collagen synthesis to promote tissue healing. Although acetic acid soaks normalize alkali wound conditions to raise tissue oxygen saturation and deconstruct the biofilms of chronic wounds, frequent dressing changes are required. Combined use of NPWT and acetic acid irrigation was assessed in the treatment of chronic wounds, instilling acetic acid solution (1%) beneath polyurethane membranes twice daily for three weeks under continuous pressure (125 mm Hg). Clinical photographs, pH levels, cultures, and debrided fragments of wounds were obtained pre- and posttreatment. Tissue immunostaining (CD31, Ki-67, and CD45) and reverse transcription-polymerase chain reaction (vascular endothelial growth factor [VEGF], vascular endothelial growth factor receptor [VEGFR]; procollagen; hypoxia-inducible factor 1 alpha [HIF-1-alpha]; matrix metalloproteinase [MMP]-1,-3,-9; and tissue inhibitor of metalloproteinase [TIMP]) were also performed. Wound sizes tended to diminish with the combined therapy, accompanied by drops in wound pH (weakly acidic or neutral) and less evidence of infection. CD31 and Ki-67 immunostaining increased (P<0.05) post-treatment, as did the levels of VEGFR, procollagen, and MMP-1 (P<0.05), whereas the VEGF, HIF-1-alpha, and MMP-9/TIMP levels declined (P<0.05). By combining acetic acid irrigation with negative-pressure dressings, both the pH and the size of chronic wounds can be reduced and infections be controlled. This approach may enhance angiogenesis and collagen synthesis in wounds, restoring the extracellular matrix.


Parenting quality and children's mental health: biological mechanisms and psychological interventions.
The quality of parenting that children receive can have a profound influence on their development and mental health. This article reviews articles published from late 2010 onwards that address the effects of parenting on the child's physiological and genetic systems, and how interventions can improve children's security of attachments, antisocial behaviour and other outcomes across a range of settings. Biological indices of stress, such as C-reactive protein, show that prenatal anxiety is a significant determinant of later outcomes for children, and abusive parenting of young children has lasting biological effects into adulthood. Increasingly, specific genes, especially those that code for neurotransmitter synthesis and functions, are being identified that moderate parenting effects. Furthermore, animal studies suggest that harsh parenting affects the expression of genes by epigenetic processes.Parenting programmes are effective in increasing the security of infant children's attachments, and reducing conduct problems/antisocial behaviour in childhood, and they can be effective at a population level in preventing abuse. These programmes are now widening their reach to cover a broader range of children's outcomes such as literacy and obesity. We are learning much more about the biological impact of poor parenting and the need for interventions that are crafted to improve the quality of parent-child relationships in many settings. Hopefully, they will also ameliorate the biological effects of poor parenting.


Which is the optimal timing for starting chemoprotection with gonadotropin-releasing hormone agonists after oocyte cryopreservation? Reflections on a critical case of ovarian hyperstimulation syndrome.
Aim of this report is to alert clinicians about the potential significant sequelae of administering depot gonadotropin-releasing hormone agonists (GnRHa) shortly after oocytes cryopreservation. In our case report, a 28-year-old nulligravid Caucasian woman diagnosed with breast cancer underwent controlled ovarian stimulation-oocyte cryopreservation before chemotherapy. The oocyte retrieval was performed without complications and the woman was discharged after five hours. Three days later, the patient self-injected depot-GnRHa as chemoprotective agent, as indicated by the oncologist. The next day, the patient referred to the emergency room and she was diagnosed with ovarian hyperstimulation syndrome (OHSS) and required inpatient care. As a consequence, the start of the chemotherapy was delayed by two weeks. In conclusion, chemoprotection with depot-GnRHa after oocyte/embryo cryopreservation is not exempt from risks. The timing for depot-GnRHa administration should be established by the agreement between oncologist and gynecologist in order to avoid the risk of OHSS.


Efficacy and safety of levomilnacipran, vilazodone and vortioxetine compared with other second-generation antidepressants for major depressive disorder in adults: A systematic review and network meta-analysis.
Second-generation antidepressants dominate the medical management of major depressive disorder (MDD). Levomilnacipran, vilazodone and vortioxetine are the latest therapeutic options approved for the treatment of MDD. This systematic review aims to compare the benefits and harms of vilazodone, levomilnacipran, and vortioxetine with one another and other second-generation antidepressants. We searched electronic databases up to September 2017 and reviewed reference lists and pharmaceutical dossiers to detect published and unpublished studies. Two reviewers independently screened abstracts and full text articles, and rated the risk of bias of included studies. Randomized controlled trials (RCTs) and controlled observational studies including adult outpatients with MDD were eligible for inclusion. We conducted network meta-analyses on response to treatment using frequentist multivariate meta-analyses models. Placebo- and active-controlled trials were eligible for network meta-analyses. Twenty-four studies met our inclusion criteria. Direct comparisons were limited to vilazodone versus citalopram, and vortioxetine versus duloxetine, paroxetine, or venlafaxine XR (extended release). Results of head-to-head trials and network meta-analyses, overall, indicated similar efficacy among levomilnacipran, vilazodone, or vortioxetine and other second-generation antidepressants. Although rates of overall adverse events and discontinuation due to adverse events were similar, RCTs reported several differences in specific adverse events. For most outcomes the strength of evidence was low. Limitations are the focus of literature searches on studies published in English, possible reporting biases, and general methodological limitations of network meta-analyses. Overall, the available evidence does not indicate greater benefits or fewer harms of levomilnacipran, vilazodone, and vortioxetine compared with other second-generation antidepressants.


Recommended survey designs for occupancy modelling using motion-activated cameras: insights from empirical wildlife data.
Motion-activated cameras are a versatile tool that wildlife biologists can use for sampling wild animal populations to estimate species occurrence. Occupancy modelling provides a flexible framework for the analysis of these data; explicitly recognizing that given a species occupies an area the probability of detecting it is often less than one. Despite the number of studies using camera data in an occupancy framework, there is only limited guidance from the scientific literature about survey design trade-offs when using motion-activated cameras. A fuller understanding of these trade-offs will allow researchers to maximise available resources and determine whether the objectives of a monitoring program or research study are achievable. We use an empirical dataset collected from 40 cameras deployed across 160 km(2) of the Western Slope of Colorado, USA to explore how survey effort (number of cameras deployed and the length of sampling period) affects the accuracy and precision (i.e., error) of the occupancy estimate for ten mammal and three virtual species. We do this using a simulation approach where species occupancy and detection parameters were informed by empirical data from motion-activated cameras. A total of 54 survey designs were considered by varying combinations of sites (10-120 cameras) and occasions (20-120 survey days). Our findings demonstrate that increasing total sampling effort generally decreases error associated with the occupancy estimate, but changing the number of sites or sampling duration can have very different results, depending on whether a species is spatially common or rare (occupancy = ψ) and easy or hard to detect when available (detection probability = p). For rare species with a low probability of detection (i.e., raccoon and spotted skunk) the required survey effort includes maximizing the number of sites and the number of survey days, often to a level that may be logistically unrealistic for many studies. For common species with low detection (i.e., bobcat and coyote) the most efficient sampling approach was to increase the number of occasions (survey days). However, for common species that are moderately detectable (i.e., cottontail rabbit and mule deer), occupancy could reliably be estimated with comparatively low numbers of cameras over a short sampling period. We provide general guidelines for reliably estimating occupancy across a range of terrestrial species (rare to common: ψ = 0.175-0.970, and low to moderate detectability: p = 0.003-0.200) using motion-activated cameras. Wildlife researchers/managers with limited knowledge of the relative abundance and likelihood of detection of a particular species can apply these guidelines regardless of location. We emphasize the importance of prior biological knowledge, defined objectives and detailed planning (e.g., simulating different study-design scenarios) for designing effective monitoring programs and research studies.


Effects of in vivo treatment with PIXY321 (GM-CSF/IL-3 fusion protein) on proliferation kinetics of bone marrow and blood myeloid progenitor cells in patients with sarcoma.
PIXY321, a stimulator of multipotent colony-forming units (CFU-GEMM), burst-forming unit-erythroid (BFU-E), and colony-forming units granulocyte/macrophage (CFU-GM) progenitor cell proliferation in vitro, is currently being assessed in phase-I/-II clinical trials. We evaluated kinetics of CFU-GEMM, BFU-E, and CFU-GM proliferation in bone marrow (BM), blood, and granulocyte (CFU-G) and macrophage (CFU-M) progenitors in BM of chemotherapy-naive patients with sarcoma-administered PIXY321 (25 to 1000 micrograms/m2/day subcutaneously for 14 days). BM and/or blood cells from three to four patients at each dosage were assessed before, during, 1 to 2 days, and 7 days following treatment with PIXY321. Cells were pulse-treated in vitro with or without high-specific activity tritiated thymidine (3H-dThr) (to assess the percentage of progenitors in S-phase of cell cycle) and cultured for immature and more mature subsets of CFU-GEMM, BFU-E, CFU-GM, and for CFU-G and CFU-M. Despite heterogeneity in baseline cycling status of progenitors in BM, administration of 125 to 500 micrograms PIXY321 to patients at least doubled (p < 0.001) cycling rates of all BM progenitors. The cycling rates of blood progenitors increased from a slow or non-cycling state to > 38% cells in cycle. Within 1 to 2 days after cessation of PIXY321 infusion, all progenitors were in a slow or noncycling phase below that of many of the pre-BM samples (immature and mature CFU-GM and mature BFU-E) or were back to background levels (CFU-G, CFU-M, CFU-GEMM, and immature BFU-E). These cycling effects were similar to those previously noted for BM CFU-GM and BFU-E in patients on clinical trial with GM-CSF. In contrast, higher dosages of PIXY321, especially 1000 micrograms, increased cycling of BM and blood progenitor cells early during treatment, but cycling rates decreased while patients were still being administered PIXY321; decreased cycling was maintained after cessation of PIXY321. PIXY321 is thus highly active in vivo as a stimulator of multipotential and more lineage-restricted progenitors. The kinetics of progenitor cell proliferation noted in this study highlight differences seen with GM-CSF and G-CSF. The effects described here could be of relevance in design of future clinical trials using PIXY321 as an adjunct treatment in patients undergoing cytoreductive therapy.


Loss of heterozygosity on the long arm of chromosome 22 in pheochromocytoma.
To identify the putative common deleted region on the long arm of chromosome 22 in pheochromocytoma, restriction fragment length polymorphism analysis was performed in 17 pheochromocytomas. All cases were heterozygous for at least one of the eight marker loci on 22q. Loss of heterozygosity (LOH) was observed in nine pheochromocytomas, of which eight were hereditary and one nonhereditary. Three pheochromocytomas had interstitial deletions that enabled us to localize the commonly deleted region as distal to D22S10 and proximal to D22S22. Hereditary pheochromocytoma frequently occurs in association with medullary thyroid carcinoma (MTC). Therefore, we also studied allelic loss on 22q in 23 hereditary MTCs. Only one of the MTCs showed LOH on 22q. Recent studies have mapped tumor suppressor loci associated with meningioma and neurofibromatosis type 2 (NF2) to 22q. The commonly deleted region in pheochromocytoma found by us encompasses the regions to which tumor suppressor genes associated with NF2 and meningioma have been mapped. The exact role of the pheochromocytoma tumor suppressor gene on 22q and its relationship to the suppressor genes involved in NF2 and meningioma remain unknown.


Disengagement from mental health treatment among individuals with schizophrenia and strategies for facilitating connections to care: a review of the literature.
Disengagement from mental health services can lead to devastating consequences for individuals with schizophrenia and other serious mental illnesses who require ongoing treatment. We review the extent and correlates of dropping out of mental health treatment for individuals with schizophrenia and suggest strategies for facilitating treatment engagement. Although rates vary across studies, reviews of the literature suggest that up to one-third of individuals with serious mental illnesses who have had some contact with the mental health service system disengage from care. Younger age, male gender, ethnic minority background, and low social functioning have been consistently associated with disengagement from mental health treatment. Individuals with co-occurring psychiatric and substance use disorders, as well as those with early-onset psychosis, are at particularly high risk of treatment dropout. Engagement strategies should specifically target these high-risk groups, as well as high-risk periods, including following an emergency room or hospital admission and the initial period of treatment. Interventions to enhance engagement in mental health treatment range from low-intensity interventions, such as appointment reminders, to high-intensity interventions, such as assertive community treatment. Disengagement from treatment may reflect the consumer's perspective that treatment is not necessary, is not meeting their needs, or is not being provided in a collaborative manner. An emerging literature on patient-centered care and shared decision making in psychiatry provides suggestive evidence that efforts to enhance client-centered communication and promote individuals' active involvement in mental health treatment decisions can also improve engagement in treatment.


Development and growth trends in angiotensin II-induced murine dissecting abdominal aortic aneurysms.
Abdominal aortic aneurysms are pathological dilations that can suddenly rupture, causing more than 15,000 deaths in the U.S. annually. Current treatment focuses on observation until an aneurysm's size warrants surgical intervention. Thus, there is a need for therapeutic intervention to inhibit growth of smaller aneurysms. An experimental aneurysm model that infuses angiotensin II into apolipoprotein E-deficient mice is widely used to investigate underlying pathological mechanisms and potential therapeutics, but this model has two caveats: (1) aneurysms do not always form, and (2) aneurysm severity and growth is inconsistent among animals. Here we use high-frequency ultrasound to collect data from angiotensin II-induced aneurysms to develop prediction models of both aneurysm formation and growth. Baseline measurements of aortic diameter, volume/length, and strain were used with animal mass and age in a quadratic discriminant analysis and logistic regression to build two statistical models to predict disease status. Longitudinal ultrasound data were also acquired from mice with aneurysms to quantify aneurysm diameter, circumferential strain, blood flow velocity, aneurysm volume/length, and thrombus and open-false lumen volumes over 28 days. Measurements taken at aneurysm diagnosis were used with branching artery information to produce a multiple linear regression model to predict final aneurysm volume/length. All three statistical models could be useful in future aneurysm therapeutic studies to better delineate the effects of preventative and suppressive treatments from normal variations in the angiotensin II aneurysm model.


Conformational heterogeneity of MHC class II induced upon binding to different peptides is a key regulator in antigen presentation and epitope selection.
T cells bearing alphabeta receptors recognize antigenic peptides bound to class I and class II glycoproteins encoded in the major histocompatibility complex (MHC). Cytotoxic and helper T cells respond respectively to peptide antigens derived from endogenous sources presented by MHC class I, and exogenous sources presented by MHC II, on antigen presenting cells. Differences in the MHC class I and class II structures and their maturation pathways have evolved to optimize antigen presentation to their respective T cells. A main focus of our laboratory is on efforts to understand molecular events in processing of antigen for presentation by MHC class II. The different stages of MHC class II-interactions with molecular chaperons involved in folding and traffic from the ER through the antigen-loading compartments, peptide exchange, and transport to the cell surface have been investigated. Through intense research on biophysical and biochemical properties of MHC class II molecules, we have learned that the conformational heterogeneity of MHC class II induced upon binding to different peptides is a key regulator in antigen presentation and epitope selection, and a determinant of the ability of MHC class II to participate in peptide association or dissociation and interaction with the peptide editor HLA-DM.


Immunochemical characterization of NADPH-cytochrome P-450 reductase from Jerusalem artichoke and other higher plants.
Polyclonal antibodies were prepared against NADPH-cytochrome P-450 reductase purified from Jerusalem artichoke. These antibodies inhibited efficiently the NADPH-cytochrome c reductase activity of the purified enzyme, as well as of Jerusalem artichoke microsomes. Likewise, microsomal NADPH-dependent cytochrome P-450 mono-oxygenases (cinnamate and laurate hydroxylases) were efficiently inhibited. The antibodies were only slightly inhibitory toward microsomal NADH-cytochrome c reductase activity, but lowered NADH-dependent cytochrome P-450 mono-oxygenase activities. The Jerusalem artichoke NADPH-cytochrome P-450 reductase is characterized by its high Mr (82,000) as compared with the enzyme from animals (76,000-78,000). Western blot analysis revealed cross-reactivity of the Jerusalem artichoke reductase antibodies with microsomes from plants belonging to different families (monocotyledons and dicotyledons). All of the proteins recognized by the antibodies had an Mr of approx. 82,000. No cross-reaction was observed with microsomes from rat liver or Locusta migratoria midgut. The cross-reactivity generally paralleled well the inhibition of reductase activity: the enzyme from most higher plants tested was inhibited by the antibodies; whereas Gingko biloba, Euglena gracilis, yeast, rat liver and insect midgut activities were insensitive to the antibodies. These results point to structural differences, particularly at the active site, between the reductases from higher plants and the enzymes from phylogenetically distant plants and from animals.


Chain-growth versus step-growth mechanisms for the Suzuki-Heck polymerisation of fluorenyldibromides with potassium vinyl trifluoroborate.
The mechanism of the Suzuki-Heck (SuHe) polymerisation of 2,7-dibromo-9,9-di(n-dodecyl)fluorene (1) with potassium vinyl trifluoroborate (PVTB) for the synthesis of poly(fluorenylene vinylene)s (PFVs) has been investigated. In the first stage, a palladium-catalysed chain-growth AA/B(C)-type polycondensation occurs, as evidenced by the linear trend observed when plotting the molecular weights of the polymer formed against the consumption of the monomer. The chain-growth stage takes place until complete consumption of 1 and allows one to envisage the alternating addition of PVTB (by a Suzuki step) and 1 (by a Heck step) to the growing chain. Such alternating addition seems to proceed through a peculiar catalyst transfer during which the metal is constantly bound to the growing chain, confirmed by MALDI end-group analysis. On prolonging the reaction after the disappearance of 1, a second stage takes place, leading to higher molecular weight polymers, which are formed by the step-growth condensation of the fragments generated in the first stage. The molecular weights of the final PFVs depend on the PVTB/1 feed ratio. Thus, by using a PVTB/1 molar ratio of 1.1, the final PFV was characterised by an M(n) of 39600 Da, whereas when using a PVTB/1 molar ratio of 2.0, the final PFV was characterised by an M(n) of 13200 Da.


Use of dominant-negative HrpA mutants to dissect Hrp pilus assembly and type III secretion in Pseudomonas syringae pv. tomato.
The Hrp pilus plays an essential role in the long-distance type III translocation of effector proteins from bacteria into plant cells. HrpA is the structural subunit of the Hrp pilus in Pseudomonas syringae pv. tomato (Pst) DC3000. Little is known about the molecular features in the HrpA protein for pilus assembly or for transporting effector proteins. From previous collections of nonfunctional HrpA derivatives that carry random pentapeptide insertions or single amino acid mutations, we identified several dominant-negative mutants that blocked the ability of wild-type Pst DC3000 to elicit host responses. The dominant-negative phenotype was correlated with the disappearance of the Hrp pilus in culture and inhibition of wild-type HrpA protein self-assembly in vitro. Dominant-negative HrpA mutants can be grouped into two functional classes: one class exerted a strong dominant-negative effect on the secretion of effector proteins AvrPto and HopPtoM in culture, and the other did not. The two classes of mutant HrpA proteins carry pentapeptide insertions in discrete regions, which are interrupted by insertions without a dominant-negative effect. These results enable prediction of possible subunit-subunit interaction sites in the assembly of the Hrp pilus and suggest the usefulness of dominant-negative mutants in dissection of the role of the wild-type HrpA protein in various stages of type III translocation: protein exit across the bacterial cell wall, the assembly and/or stabilization of the Hrp pilus in the extracellular space, and Hrp pilus-mediated long-distance transport beyond the bacterial cell wall.


Myocardial infarction after percutaneous coronary intervention: a meta-analysis of troponin elevation applying the new universal definition.
Elevation of Troponin after scheduled percutaneous coronary intervention (PCI) is a recognized consequence. We sought to evaluate the prognostic significance and impact of the newly published definition of PCI-related myocardial infarction (MI) according to which any troponin elevation >3 times the upper reference limit identify a peri-procedural MI. Search of BioMedCentral, CENTRAL, mRCT and PubMed (updated May 2008). Outcomes of interest were: MACE [the composite of all cause death, MI, repeat target vessel PCI (re-PCI) and coronary artery bypass grafting (CABG)]; single end points were also assessed. Fifteen studies have been included totalling 7578 patients. Troponin elevation occurred in 28.7% of the procedures. The incidence of PCI-related MI according to the new definition was 14.5%. During the hospitalization, any level of raised troponin was associated with an increased risk of MACE [OR 11.29 (3.00-42.48), Number needed to harm (NNH) 5], death [OR 7.16 (1.95-26.27), NNH = 100], MI [OR 30.85 (6.05-157.38), NNH = 4] and re-PCI [OR 4.13 (1.23-13.88), NNH = 50]. Patients with PCI-related MI had an increased risk of death [OR 17.25 (2.71-109.96), NNH = 100] and re-PCI [OR 10.86 (3.2-36.94), NNH = 25]. At follow up of 18 months any troponin elevation was associated with an increased risk of MACE [OR 1.48 (1.12-1.96), NNH = 20], death [OR 2.19 (1.59-3.00), NNH = 50], MI [OR 3.29 (2.71-6.31), NNH = 33] and re-PCI [OR 1.47 (1.06-2.03), NNH = 25]. In patients with PCI-related MI the risk of MACE was further increased: OR 2.25 (1.26-4.00), NNH = 3. An increase of the troponin level below the cut-off was not associated with MACE. A diagnosis of MI according to the new guidelines applies to 15% of patients undergoing PCI and these patients are at high risk of further adverse events both during the hospital stay and at 18 months.


Atg27 tyrosine sorting motif is important for its trafficking and Atg9 localization.
During autophagy, the transmembrane protein Atg27 facilitates transport of the major autophagy membrane protein Atg9 to the preautophagosomal structure (PAS). To better understand the function of Atg27 and its relationship with Atg9, Atg27 trafficking and localization were examined. Atg27 localized to endosomes and the vacuolar membrane, in addition to previously described PAS, Golgi and Atg9-positive structures. Atg27 vacuolar membrane localization was dependent on the adaptor AP-3, which mediates direct transport from the trans-Golgi to the vacuole. The four C-terminal amino acids (YSAV) of Atg27 comprise a tyrosine sorting motif. Mutation of the YSAV abrogated Atg27 transport to the vacuolar membrane and affected its distribution in TGN/endosomal compartments, while PAS localization was normal. Also, in atg27(ΔYSAV) or AP-3 mutants, accumulation of Atg9 in the vacuolar lumen was observed upon autophagy induction. Nevertheless, PAS localization of Atg9 was normal in atg27(ΔYSAV) cells. The vacuole lumen localization of Atg9 was dependent on transport through the multivesicular body, as Atg9 accumulated in the class E compartment and vacuole membrane in atg27(ΔYSAV) vps4Δ but not in ATG27 vps4Δ cells. We suggest that Atg27 has an additional role to retain Atg9 in endosomal reservoirs that can be mobilized during autophagy.


Management of Descending Thoracic Aortic Diseases: Similarities and Differences Among Cardiovascular Guidelines.
Cardiovascular societies have developed recommendations regarding the management of thoracic aortic diseases. While improvements in treatment have been observed during the past decade in regard to patient selection, thoracic endovascular aortic repair (TEVAR) and associated techniques, and high-volume centralization, the broad expansion of TEVAR has raised considerations about its indications, appropriateness, limitations, and application. The aim of this systematic review was to assess the similarities and differences among current cardiovascular societies' guidelines for the management of thoracic aortic diseases. The MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials were searched from January 2009 to May 2020. The initial search identified 990 articles. After exclusion of duplicate or inappropriate articles, the final analysis included 5 articles from cardiovascular societies published between 2010 and 2020. Selected controversial topics were analyzed, including diagnosis, imaging, spinal cord ischemia prevention, and management of the most important thoracic aortic pathologies. The analysis included data concerning the therapeutic approach in acute and chronic type B aortic dissection, penetrating aortic ulcer, intramural hematoma, thoracic aortic aneurysm, and traumatic aortic injury, as well a discussion of inflammatory aneurysms, aortitis, and genetic syndromes. The review presents consistent and controversial recommendations, as well as "gray zone" issues that need further investigation. There was significant overlap and agreement among the 5 societies regarding the management of thoracic aortic diseases. Especially in dissection and aneurysm management, TEVAR has established its role as the treatment of choice. However, robust evidence is still needed in many aspects of the management of thoracic aortic pathologies.


Hepatic perfusion index in evaluating treatment effect of transcatheter hepatic artery embolization in patients with hepatocellular carcinoma.
We assumed the hepatic perfusion index (HPI) in patients with hepatocellular carcinoma (HCC) treated by transcatheter arterial embolization (TAE) and compared the results with the following CT findings. From September 1993 to February 1994, 15 patients with newly diagnosed HCC, proven by biopsy, were studied. Hepatic perfusion index (HPI) studies were performed before-TAE as well as on the 1st day and 7th day post-TAE, and CT scans were performed before and one month after the TAE. HPI at 1st-day post-TAE (HPI1) over HPI pre-TAE (HPIp) and HPI at 7th-day post-TAE (HPI7) over HPIp were calculated. The HPI7/HPIps were chosen to evaluate the efficacy of TAE because they had better correlation with the CT findings than HPI1/HPIps. CT scans performed one month after the TAE showed obvious reduction of tumor size in all 7 patients with a HPI7/HPI p < 0.85 but in only 2 of the 7 patients with a HPI7/HPI p > or = 0.85. The difference was significant, with a p-value of 0.01 by Fisher's exact test. We consider that the HPI with its characteristics of relative safety, convenience, low radiation exposure, and inexpense, may provide an useful modality for early prediction of the efficacy of hepatic artery embolization in the treatment of HCC.


Air pollution and cause-specific mortality in Milan, Italy, 1980-1989.
In several studies, investigators have reported associations among air pollution, weather, and daily deaths, usually from all causes. In the current study, we focused on the difference in lag time between exposure to total suspended particulates or extreme weather and cause-specific mortality in an effort to understand the potential underlying mechanism. We used a robust Poisson regression in a generalized additive model to investigate the association between air pollution and daily mortality. We used a loess smooth function to model season, weather, and humidity; indicator variables for hot days were also used. To examine the relationship in a currently meaningful range, we excluded all days with a total suspended particulate concentration higher than 200 microg/m3. We found a significant association on the concurrent day, both for respiratory infection deaths (11% increase/100 microg/m3 increase in total suspended particulate; 95% confidence interval = 5, 17) and for heart-failure deaths (7% increase; 95% confidence interval = 3, 11). The associations with myocardial infarction (i.e., 10% increase; 95% confidence interval = 3, 18) and chronic obstructive pulmonary disease (12% increase, 95% confidence interval = 6, 17) were found for the means of 3 and 4 d prior to death. We observed an effect of cold weather at lag 1 for respiratory infections and an effect of hot weather at lag 0 for heart failure and myocardial infarctions. The association for all causes and cause-specific deaths was almost identical to that noted previously in Philadelphia, Pennsylvania. Smoothed functions of total suspended particulates suggested a higher slope at lower concentrations, and this finding may account for differences noted between European and U.S. studies. Given that both the dependence between weather and daily mortality and the lag between exposure and death varies by cause of death, analyses by specific causes of death would be very useful in the future.


Interleukin-1 beta enhances spinal cord blood flow after intrathecal administration in the normal rat.
The effects of acute intrathecal recombinant human interleukin-1 beta (rhIL-1 beta) administration on spinal cord blood flow (SCBF), volume, and velocity were determined by laser-Doppler flowmetry in normal anesthetized rats with the use of a randomized and blinded protocol. The intrathecal administration of rhIL-1 beta (0.16-16 ng) produced a dose-dependent increase in SCBF that was not related to changes in blood pressure; arterial pH, PO2, PCO2; or spinal cord temperature. The IL-1 beta-induced enhancement of SCBF was directly proportional to the resultant elevation of spinal cord rhIL-1 beta content and was significantly correlated with an elevated blood velocity. The IL-1 receptor antagonist (IL-1ra) in concentrations 50- and 200-fold higher than IL-1 beta completely blocked the IL-1 beta-induced increase in SCBF when both compounds were administered concomitantly, but when administered alone, IL-1ra did not affect SCBF or other parameters. This suggests that IL-1 beta action was mediated by a specific interaction with an IL-1 membrane receptor site. The results suggest a role of IL-1 beta in the regulation of spinal cord hemodynamics. A potential pharmacological approach using IL-1 agonists for the treatment of the delayed appearance of posttraumatic spinal ischemia is proposed.


Biomechanical Analysis of Lumbar Interbody Fusion Cages With Various Elastic Moduli in Osteoporotic and Non-osteoporotic Lumbar Spine: A Finite Element Analysis.
Finite element analysis (FEA). This study aimed to explore the effects of cage elastic modulus (Cage-E) on the endplate stress in different bone conditions: osteoporosis (OP) and non-osteoporosis (non-OP). We also explored the correlation between endplate thickness and endplate stress. The FEA models of L4-L5 with lumbar interbody fusion were designed to access the effects of Cage-E on the endplate stress in different bone conditions. Two groups of the Young's moduli of bony structure were assigned to simulate the conditions of OP and non-OP, and the bony endplates were analyzed in 2 kinds of thicknesses: .5 mm and 1.0 mm, with the insertion of cages with different Young's moduli including .5, 1.5, 3, 5, 10, and 20 GPa. After model validation, an axial compressive load of 400 N and a flexion/extension moment of 7.5Nm was performed on the superior surface of L4 vertebral body in order to analyze the distribution of stress. The maximum Von Mises stress in the endplates increased by up to 100% in the OP model compared with non-OP model under the same condition of cage-E and endplate thickness. In both OP and non-OP models, the maximum endplate stress decreased as the cage-E decreased, but the maximum stress in the lumbar posterior fixation increased as the cage-E decreased. Thinner endplate thickness was associated with increased endplate stress. The endplate stress is higher in osteoporotic bone than non-osteoporotic bone, which explains part of the mechanism of OP-related cage subsidence. It is reasonable to reduce the endplate stress by reducing the cage-E, but we should balance the risk of fixation failure. Endplate thickness is also important when evaluating the cage subsidence risk.


SDHD gene mutation in Mexican population with carotid body tumor.
Among the U.S. population, the p81L SDHD (11q23) gene mutation is present in 6-36% of patients with sporadic carotid body tumor (CBT), but in familial cases is high as 80%. That is why the P81L mutation is used as a screening method for carotid body tumor in the U.S. We included 25 patients who underwent resection of a CBT from January 2010 to June 2015. After informed consent, a blood sample was taken for genetic testing on real-time polymerase chain reaction, in order to identify p81L mutation in the SDHD gene. The information was analyzed with descriptive statistics, using central tendency and description measures. In our group, 92% were females, a mean age of 55.5 years, and 52% were Shamblin type II. The most common place of residence was Mexico City, 8% of the patients had family history, about 20% of the patients had a contralateral tumor and 16% had antecedent of another kind of tumor, 4 (16%) p81L SDHD gene mutations were detected, all of them were heterozygous. The p81L mutation in the SDHD gene was found in the Mexican population in higher grade that in the U.S. population, which explain the high incidence of this pathology in our country, but we need more studies about this subject.


Randomized, Placebo-Controlled Prospective Clinical Trial Evaluating the Efficacy of the Assisi Anti-anxiety Device (Calmer Canine) for the Treatment of Canine Separation Anxiety.
Introduction: Separation anxiety (SA) is among the most common canine behavior disorders and affects quality-of-life for dogs and their owners. Dogs with SA show signs of anxiety during absence or perceived absence of their owners. While psychoactive medications are often helpful for treating SA, dog and human factors may limit their utility. This study explored the efficacy of a pulsed electromagnetic field (PEMF) device for treatment of canine SA. Materials and Methods: In this double-blind randomized placebo-controlled study, a screening questionnaire and baseline video confirmed the diagnosis of SA. Owners treated their dog with the device twice daily for 6 weeks, completed weekly questionnaires, and noted adverse events. Videos were taken of the dog while alone at weeks 4 and 6. Behaviors were coded and categorized as negative and positive. Questionnaire and video data at weeks 4 and 6 were compared to baseline. Results: Forty client-owned dogs with moderate to severe SA completed the study. There were no differences between groups for age, weight, or sex. In owner questionnaires, no difference in behavior or overall score was found between the active and sham groups (p > 0.05). Videos of the active group compared to the sham group showed significant reduction in negative behaviors by week 6 (p = 0.036) and higher percentage of success at week 4 (Z = 2.83, p = 0.005), at week 6 (Z = 1.65, p = 0.098), and across the full study (Z = 1.99, p = 0.047). Adverse events were reported in eight dogs (6 active, 2 sham); all resolved and were unlikely to be related to treatment. Discussion: This study supports the efficacy and safety of this PEMF device for treatment of SA in dogs. Questionnaire results may not be sensitive enough to detect subtle negative behavioral states compared to video, and may not capture other owner observed behavioral changes. A caregiver placebo effect may account for some improvement seen in both groups. Video data appear better for diagnosis and monitoring dog's behavior when left alone. Future studies should assess PEMF's impact on other anxieties or combination of anxiety disorders in dogs.


Functional characterization of coat protein and V2 involved in cell to cell movement of Cotton leaf curl Kokhran virus-Dabawali.
The functional attributes of coat protein (CP) and V2 of the monopartite begomovirus, Cotton leaf curl Kokhran virus- Dabawali were analyzed in vitro and in vivo by their overexpression in E. coli, insect cells and transient expression in the plant system. Purified recombinant V2 and CP proteins were shown to interact with each other using ELISA and surface plasmon resonance. Confocal microscopy of Sf21 cells expressing V2 and CP proteins revealed that V2 localized to the cell periphery and CP to the nucleus. Deletion of the N terminal nuclear localization signal of CP restricted its distribution to the cytoplasm. GFP-V2 and YFP-CP transiently expressed in N. benthamiana plants by agroinfiltration substantiated the localization of V2 to the cell periphery and CP predominantly to the nucleus. Interestingly, upon coinfiltration, CP was found both in the nucleus and in the cytoplasm along with V2. These results suggest that the interaction of V2 and CP may have important implications in the cell to cell movement.


Theoretical and Experimental Investigations of Tool Tip Vibration in Single Point Diamond Turning of Titanium Alloys.
The material swelling effect in single point diamond turning (SPDT) causes ragged materials on a machined surface which slows down the movements of tool tip vibration, and acts as a simple impacted pendulum system with a damping effect and displays a single twin peak in fast Fourier transform (FFT). Due to the low elastic modulus and low thermal conductivity of titanium alloys, the material swelling effect of titanium alloys in SPDT is much more serious than that of traditional metals. For this reason, the tool tip vibration in SPDT of titanium alloys is expected to be different from previous reports. In this study, apart from the demonstration of the original single twin peak induced from the material swelling effect by the main cutting motion, we reported recently that there exists another twin peak induced by secondary material swelling arising from the movement of tool tip vibration in the SPDT of titanium alloys. The additional twin peak was located at the right side of the original twin peak in FFT, displaying two twin peaks in the frequency domain of cutting force and suggesting the existence of another tool tip vibration system with a new damping factor in the SPDT of titanium alloys. Combining the effects of primary and secondary material swelling, the new dynamic model with the modified damping factor of tool tip vibration system are developed, which surface roughness of the machined titanium alloys in SPDT was predicted in higher accuracy by using the new model. The FFT of cutting force, surface roughness, and surface profile were provided in this article for the experimental validations.


Three-dimensional structure of soybean beta-amylase determined at 3.0 A resolution: preliminary chain tracing of the complex with alpha-cyclodextrin.
The three-dimensional structure of a complex of soybean beta-amylase [EC 220.127.116.11] with an inhibitor, alpha-cyclodextrin, has been determined at 3.0 A resolution by X-ray diffraction analysis. Preliminary chain tracing showed that the enzyme folded into large and small domains. The large domain has a (beta alpha)8 super-secondary structure, while the smaller one is formed from two long loops extending from the beta 3 and beta 4 strands of the (beta alpha)8 structure. The interface of the two domains together with shorter loops from the (beta alpha)8 structure form a deep cleft, in which alpha-cyclodextrin binds slightly away from the center. Two maltose molecules also bind in the cleft. One shares a binding site with alpha-cyclodextrin and the other is situated more deeply in the cleft.


Is battered women's help seeking connected to the level of their abuse?
A total of 289 abused women who sought assistance in several battered women's agencies were interviewed. Of these abused women, 70 percent reported a delay of more than a year in seeking help from the agency, even though many of them reported having experienced severe or life threatening abuse. There was no association between the severity of abuse and the time lapsed in seeking help from an agency, indicating that women exposed to severe, life-threatening physical abuse frequently delay help seeking. Increased attention to barrier to help seeking among battered women and approaches to increasing the accessibility of services for battered women seem warranted.


Roles of beta2-adrenergic receptor gene polymorphisms in a Turkish population with obstructive sleep apnea syndrome or obesity.
We determined the distribution of the Arg16Gly and Gln27Glu polymorphisms of the beta-2 adrenergic receptor gene (ADRB2) in patients with obstructive sleep apnea syndrome as well as a control group in Northeastern Turkey. A total of 52 patients diagnosed with obstructive sleep apnea in a sleep laboratory and 78 control subjects were examined. Peripheral blood samples were taken from patients diagnosed with obstructive sleep apnea by polysomnography. DNA was extracted from blood samples and amplified using polymerase chain reaction. Amplification products were digested with restriction enzymes to investigate gene polymorphisms. Restriction products were extracted from agarose gel electrophoresis and polymorphisms were analyzed using gel images. The Arg16Gly polymorphism was observed in 18 of 52 patients and in 23 of 78 controls. The Gln27Glu polymorphism was observed in 21 of 52 patients and in 28 of 78 controls. In conclusion, there was no correlation among polymorphic frequencies between patient and control groups. Based on the results, these polymorphisms do not contribute to the clinical diagnosis of this syndrome. However, the distribution of Arg16Gly vs Gln27Glu polymorphisms may contribute to obesity in patients with a body mass index greater than 30 (P < 0.05). Different results may be obtained if the parameters of obstructive sleep apnea disease are changed.


Microwave Irradiation Process for Al-Sc Alloy Production.
Scandium is being explored as an alloying element for aluminium alloys, which are gaining importance as high-performance lightweight structural alloys in the transportation industry. Sc-rich ScAlN thin films show strong piezoelectricity and can be fabricated on a hard substrate for use as wideband surface acoustic wave filters in next-generation wireless mobile communication systems. However, the use of ScAlN thin films in microelectromechanical system devices is limited by the high cost of metallic Sc, which is due to the difficulty in smelting of this material. Here, we propose a novel microwave irradiation process for producing Al-Sc alloys, with Mg ions as a reducing agent. Although scandium oxide is thermodynamically stable, intermetallic Al3Sc is obtained in high yield (69.8%) via a low-temperature (660 °C) reduction reaction under microwave irradiation. Optical spectroscopy results and thermodynamic considerations suggest a non-thermal equilibrium reaction with the univalent magnesium ions excited by microwave irradiation.


"Avoidable" mortality and health services: a review of aggregate data studies.
The aim of the study was to review published work reporting mortality from conditions amenable to medical intervention and compare the methods used and the results obtained. SOURCE MATERIAL: Two types of analysis were examined: (1) analyses of time trends, relating decline in mortality from amenable conditions to improvements in medical care (3 papers); (2) analyses of geographical variation, either between or within countries, in which mortality was related to the availability of health care resources and to other factors (8 papers). Time-trend studies have in general shown that mortality from amenable causes has declined faster over the past decades than most other causes of death. Studies of geographical variation have shown that mortality from amenable causes is consistently associated with socioeconomic factors, and that the association with the provision of health care resources is rather weak and inconsistent. (1) The low levels of mortality from amenable causes which presently prevail in industrialised countries are likely to reflect, at least in part, the increased effectiveness of health services; (2) geographical variation in mortality from amenable causes has not yet been shown to reflect differences in effectiveness of health services; and (3) if geographical variation in avoidable mortality does reflect such differences, they must arise from circumstances other than the level of supply, for example from more specific aspects of health care delivery, and are probably closely related to socioeconomic circumstances. In depth studies at the individual level are now more likely to produce information about factors limiting the effectiveness of health services than further studies of aggregate data.


Harmonic optical tomography of nonlinear structures.
Second-harmonic generation microscopy is a valuable label-free modality for imaging non-centrosymmetric structures and has important biomedical applications from live-cell imaging to cancer diagnosis. Conventional second-harmonic generation microscopy measures intensity signals that originate from tightly focused laser beams, preventing researchers from solving the scattering inverse problem for second-order nonlinear materials. Here, we present harmonic optical tomography (HOT) as a novel modality for imaging microscopic, nonlinear and inhomogeneous objects. The HOT principle of operation relies on inter-ferometrically measuring the complex harmonic field and using a scattering inverse model to reconstruct the three-dimensional distribution of harmonophores. HOT enables strong axial sectioning via the momentum conservation of spatially and temporally broadband fields. We illustrate the HOT operation with experiments and reconstructions on a beta-barium borate crystal and various biological specimens. Although our results involve second-order nonlinear materials, we show that this approach applies to any coherent nonlinear process.


Tepidiphilus olei sp. nov., isolated from the production water of a water-flooded oil reservoir in PR China.
A novel, moderately thermophilic, Gram-stain-negative bacterium, designated strain J18T, was isolated from a water-flooded oil reservoir. Cells were aerobic, oxidase- and catalase-positive, with a polar flagellum. Growth occurred at 35-60 °C and at pH 6-8.5. The respiratory quinones were ubiquinone 8 and ubiquinone 9. The dominant cellular fatty acids were C16 : 0, C17 : 0 cyclo, C19 : 0 cyclo ω8c and summed feature 8 (C18 : 1 ω7c/C18 : 1 ω6c). The polar lipids consisted of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine, an unidentified aminolipid, an unidentified phospholipid and an unidentified aminophospholipid. The strain showed the highest 16S rRNA gene sequence similarities to Tepidiphilus margaritifer DSM 15129T (98.6 %), Tepidiphilus succinatimandens DSM 15512T (98.4 %) and Tepidiphilus thermophilus DSM 27220T (98.1 %), respectively, and the similarity to other species was lower than 93 %. In the phylogenetic trees, it constituted a unique sub-cluster within the genus Tepidiphilus. The DNA G+C content of strain J18T was 64.44 mol%. As compared with the type strains, the genome-to-genome distances of strain J18T were 34.7-40 %. These results confirmed the separate species status of J18T with its close relatives. On the basis of physiological, chemotaxonomic and phylogenetic analyses along with the low levels of identity at the whole-genome level, it can be concluded that strain J18T represents a new species of the genus Tepidiphilus, for which the name Tepidiphilus olei sp. nov. is proposed. The type strain of T. olei is J18T (=CGMCC 1.16800T=LMG 31400T).


In Vitro Characterization and Stability Profiles of Antibody-Fluorophore Conjugates Derived from Interchain Cysteine Cross-Linking or Lysine Bioconjugation.
Fluorescent labelling of monoclonal antibodies (mAbs) is classically performed by chemical bioconjugation methods. The most frequent labelling technique to generate antibody-fluorophore conjugates (AFCs) involves the bioconjugation onto the mAb lysines of a dye bearing an N-hydroxysuccinimide ester or an isothiocyanate group. However, discrepancies between labelling experiments or kits can be observed, related to reproducibility issues, alteration of antigen binding, or mAb properties. The lack of information on labelling kits and the incomplete characterization of the obtained labelled mAbs largely contribute to these issues. In this work, we generated eight AFCs through either lysine or interchain cysteine cross-linking bioconjugation of green-emitting fluorophores (fluorescein or BODIPY) onto either trastuzumab or rituximab. This strategy allowed us to study the influence of fluorophore solubility, bioconjugation technology, and antibody nature on two known labelling procedures. The structures of these AFCs were thoroughly analyzed by mass spectroscopy, and their antigen binding properties were studied. We then compared these AFCs in vitro by studying their respective spectral properties and stabilities. The shelf stability profiles and sensibility to pH variation of these AFCs prove to be dye-, antibody- and labelling-technology-dependent. Fluorescence emission in AFCs was higher when lysine labelling was used, but cross-linked AFCs were revealed to be more stable. This must be taken into account for the design of any biological study involving antibody labelling.