Rosaniline Hydrochloride Encapsulated MCM-48: Fluorescent and Electrochemical Sensor for Dopamine.
The dye Rosaniline hydrochloride (RANH) has been successfully incorporated in MCM-48 (designated as RANH@MCM-48) and characterized by various spectroscopic methods including FT-IR, SEM, EDX and N2 adsorption-desorption isotherm. RANH@MCM-48 in aqueous medium acts as fluorescence "on" sensor for neurotransmitter dopamine (DA) in presence of its main biological interfering agent ascorbic acid or vitamin c (AA) along with Glucose, Cholesterol and Uric acid (UA). The limits of detection (LOD) were found to be 65 nM and 51 nM respectively in absence and in presence of AA. The interaction of DA to RANH@MCM-48 is found to be reversible with respect to EDTA2-. The fluorescence intensity vs. pH plot shows a narrow fluorescence window of 7.2 to 8.8. RANH@MCM-48 has been successfully applied for DA detection in artificial cerebrospinal fluid (ACF) and bovine serum albumin (BSA) with LOD values 27 nM and 22.5 nM respectively. Platinum disc electrode has been modified with RANH@MCM-48 which showed distinct oxidation peaks with a separation of 0.188 V in cyclic voltammetry (CV). The LOD for DA in presence of AA determined from oxidation current is 77.5 nM. The voltammetric detection of DA is found to be free from common interfering species Na+, K+, Ca2+, Fe2+, UA, Cholesterol and Glucose. RANH@MCM-48 has been found to be a very effective fluorescence and voltammetric sensor for DA with very low LOD.


Antitumor activity of 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) and 1-(2-chloroethyl)-3-(4-methyl-cyclohexyl)-1-nitrosourea (MeCCNU) on Yoshida sarcoma ascites cells implanted into the colon wall of rats.
Three thousand Yoshida sarcoma cells were inoculated into the wall of the descending colon of each of 120 male Sprague-Dawley rats. On day 8 after the tumor implantation, the animals were at random divided into four groups of 30 rats each. The effect of cyclophosphamide (70 mg/kg), BCNU (25 mg/kg), and methyl-CCNU (45 mg/kg) after single i.p. application was investigated. The Yoshida sarcoma transplanted into the colon is sensitive to all three chemotherapeutic drugs. At the doses given cyclophosphamide showed the best results. The two nitrosoureas had a comparable antitumor activity but methyl-CCNU showed a more distinct toxic effect. The introduction of this model for testing new cytostatics in animal experiments is discussed.


Binding of an antiviral agent to a sensitive and a resistant human rhinovirus. Computer simulation studies with sampling of amino acid side-chain conformation. I. Mapping the rotamers of residue 188 of viral protein 1.
The mutation of valine 188 to leucine in the viral protein 1 of human rhinovirus 14 renders the virus resistant to certain antiviral compounds. Thermodynamic-cycle perturbation theory provides a means of calculating the difference in the binding free energies of an antiviral compound to the wild-type virus and to the mutant virus. In calculating the relevant free-energy differences in molecular dynamics simulations, it is important to sample the multiple rotational isomers of residue 188 correctly. In general, these rotamers will not be fully sampled during a single molecular dynamics simulation. However, the contributions of all the rotamers to the free-energy differences associated with mutation of residue 188 may be considered explicitly once they have been identified and their relative free energies determined. Therefore, we describe here the mapping of the rotamers of residue 188 by steric-bump search and energy minimization techniques, and by the computation of potentials of mean force (p.m.f.s.) using umbrella sampling. The usefulness, validity and efficiency of these methods of examining rotameric states is discussed. Adiabatic mapping by energy minimization was found to be unreliable for this residue due to the small magnitude of its interactions with the surrounding protein atoms. Ambiguities in the adiabatic maps were resolved by computing p.m.f.s. The p.m.f. for valine 188 in the unliganded wild-type virus shows a minimum corresponding to the crystallographically observed conformation of valine 188. The p.m.f.s. for valine 188 in the liganded virus and for leucine 188 in the unliganded mutant virus suggest that the experimentally observed conformations may be interpreted as averages of a number of conformations corresponding to those at the minima in the p.m.f.s. The calculations suggest also that the conformation of leucine 188 may change when the ligand binds. The use of the calculated p.m.f.s. to compute the difference in the free energy of binding of an antiviral compound to the wild-type and mutant rhinoviruses is described in the accompanying article.


Intersectionality of cultural norms and sexual behaviours: a qualitative study of young Black male students at a university in KwaZulu-Natal, South Africa.
Sexual risk behaviours that occur among young men are based on dominant notions and practices that prevail in cultural contexts. As such, understanding the intersection of cultural norms and sexual risk behaviours among young men is very important. The study used a qualitative design and conducted four focus group discussions with 36 male students who were purposively selected from different levels of study at the University of KwaZulu-Natal. Data were analysed through line-by-line coding, and grouped into emerging themes and sub-themes facilitated by the use of Atlas.ti. The findings emphasize that socialisation agents such as the family, peers and community play an important role in prescribing acceptable and unacceptable sexual behaviour of young men. Some of the young men seemed to adhere to prescribed gender norms of what it means to be a man while some rejected them for alternative versions of being a man. In the context of the university environment, these findings reveal that male students cannot make informed decisions regarding condom use when they are intoxicated, and thus expose themselves to sexually transmitted infections and other risks. University sexual risk reduction programs should be developed considering the specific cultural context, using strategies that empower young men to challenge the widely accepted cultural norms that may predispose them to sexual risks. Sexual behaviours and cultural norms are interconnected, it is through culture that people learn how to behave and understand the world around them. In many cultural contexts, young men are taught from a very young age how to behave based on dominant notions of what it means to be a man in that particular context. As such, in some cultural context sexual risk-taking such as having multiple sexual partners and unprotected sex are perceived as normal behaviour for men. Some young men embrace such normalised sexual behaviours which often has negative implications on their future. This study explored the influence of cultural norms on the sexual behaviour of young men. This qualitative study was conducted at the University of KwaZulu-Natal. Four focus group discussions were conducted among first-year students to postgraduate students who were between the ages of 18 to 30 years. Our findings revealed that there other influences on the sexual behaviours of the young men, which included family, community and peers. It also emerged that gender norms regarding what it means to be a man still prevailed which some of the young men in the study adhered to, notably such notions seemed to be rejected by some of them. The university setting appeared to be space where a lot of sexual risk-taking took place, which potentially exposed the young men in the study to many sexual risks. In conclusion, targeted programs for the university setting should aim to challenge gender norms that expose young men to sexual risks.


High-quality draft genome sequence of the Opitutaceae bacterium strain TAV1, a symbiont of the wood-feeding termite Reticulitermes flavipes.
Microbial communities in the termite hindgut are essential for degrading plant material. We present the high-quality draft genome sequence of the Opitutaceae bacterium strain TAV1, the first member of the phylum Verrucomicrobia to be isolated from wood-feeding termites. The genomic analysis reveals genes coding for lignocellulosic degradation and nitrogen fixation.


Effects on pancreatic Beta and other Islet cells of the glucose-dependent insulinotropic polypeptide.
Glucose-dependent insulinotropic polypeptide (GIP) is a gut-derived incretin that, in common with glucagon-like peptide-1 (GLP-1), has both insulin releasing and extra-pancreatic glucoregulatory actions. GIP is released in response to glucose or fat absorption and acts on the GIP receptor (GIPR) to potentiate insulin release from pancreatic beta cells. GIP has also been shown to promote beta cell survival and stimulate the release of GLP-1 from islet alpha cells. There is now evidence to suggest that low levels of GIP are secreted from alpha cells and may act in a paracrine manner to prime neighboring beta cells for insulin release. In addition, GIP acts on adipocytes to stimulate fat storage and can exert anorexigenic effects via actions in the hypothalamus. Contrary to GLP-1, the development of effective GIP-based T2D treatments has been hindered by poor bioavailability and attenuation of beta cell responses to GIP in some patients with sub-optimally controlled T2D. Recently, longer-acting GIP agonists that exhibit enzymatic stability, as well as dual GLP-1/GIP agonists which provide simultaneous improvement in glucose and weight control have been generated and successfully tested in animal T2D models. This, together with reports on GIP antagonists that may protect against obesity, has revived the interest on the GIP/GIPR axis as a potential anti-diabetic pathway. In this review, we summarize the known aspects of the effects of GIP on beta and other islet cells and discuss the most recent developments on GIP-based therapeutic agents for the improvement of beta cell function in T2D patients.


Spatiotemporal path discontinuities of wavepackets propagating across a meta-atom.
The realization of phase discontinuities across metasurfaces has led to a new class of reflection and refraction. Here we present theory and experiment on the discontinuous propagation of wavepackets across subwavelength-thickness meta-atoms. Using acoustic waves, we observe the process of wavepackets traversing a meta-atom with abrupt displacements, which appear as path discontinuities on a space-time diagram. We construct a tunable meta-atom from two coupled resonators at ~500 Hz, map the spatiotemporal trajectories of individual sonic pulses, and reveal discontinuities at the meta-atom where the pulses exit at a time ~50 ms ahead or behind their arrivals. Applications include thin acoustic metasurface lenses.


Monitoring macroplastic ingestion by birds and marine mammals in northeastern Patagonia, Argentina.
Plastic debris is of particular concern due to its abundance, and its persistence in the environment. In Argentina, the impact of plastic debris has been documented with a significant increase during the last years. However, evidence of debris ingestion remains low compared to other regions of the world. Between 2020 and 2022, one of the twenty-three individuals analyzed in this study (seven species: five birds and two marine mammals) had ingested plastic debris. A single macroplastic piece was found in the Great Grebe (Podiceps major). It was a hardy yellow elastic band that appears to be a packaging band in agreement with the debris category with the greatest number of reports. This study is a contribution to the few records of plastic ingestion in birds, on the east coast of South America.


The Influence of Neurological Disorders Before Cardiac Myxoma Surgery on the Rate of Postoperative Recurrences: Analysis of 317 Patients in a Single Center.
Cardiac myxoma is a very rare disease for which resection is the gold standard treatment. Many neurological manifestations are associated with this disease, including embolic infarctions, arterial aneurysms, and brain metastatic myxomas, but few large-scale studies have addressed this. The aim of this study was to retrospectively analyze the incidence, type, and prognosis of these neurological disorders. We enrolled 317 patients who underwent a cardiac myxoma resection between 2004 and 2019 at our institution. A retrospective review of medical records and radiological imaging was performed for each patient, and clinical factors were compared and analyzed with regard to clinical outcomes and the incidence of adverse events. Patients with a neurological disorder before surgery were found to be more likely to develop new postoperative neurological complications (P = 0.003). Patients with a neurological disorder arising at any time before or after surgery had poorer outcomes (P < 0.001). The clinical management of cardiac myxoma must take account of neurological sequelae independently of the surgical intervention to remove the lesion. Patients with cardiac myxoma and any neurological disorder should undergo both neurosurgical follow-up and cardiac surgical follow-up, even if myxoma removal surgery has been performed. We recommend active neuroimaging during long-term follow-up as essential in these cases.


An oncolytic virus-delivered TGFβ inhibitor overcomes the immunosuppressive tumor microenvironment.
While checkpoint blockade immunotherapies have widespread success, they rely on a responsive immune infiltrate; as such, treatments enhancing immune infiltration and preventing immunosuppression are of critical need. We previously generated αPD-1 resistant variants of the murine HNSCC model MEER. While entirely αPD-1 resistant, these tumors regress after single dose of oncolytic vaccinia virus (VV). We then generated a VV-resistant MEER line to dissect the immunologic features of sensitive and resistant tumors. While treatment of both tumor types induced immune infiltration and IFNγ, we found a defining feature of resistance was elevation of immunosuppressive cytokines like TGFβ, which blunted IFNγ signaling, especially in regulatory T cells. We engineered VV to express a genetically encoded TGFβRII inhibitor. Inhibitor-expressing VV produced regressions in resistant tumor models and showed impressive synergy with checkpoint blockade. Importantly, tumor-specific, viral delivery of TGFβ inhibition had no toxicities associated with systemic TGFβ/TGFβR inhibition. Our data suggest that aside from stimulating immune infiltration, oncolytic viruses are attractive means to deliver agents to limit immunosuppression in cancer.


[Synthesis of 2,3-diazaphenothiazine. XII. Dialkylaminoalkylic derivatives of 2-phenyl and 3-phenyl-10-methyl-2,3-dihydropyridazino/4,5-b/ /1,4/benzothiazin-1,4 (10 H)-dione].
The alkylation with methyl iodide and methyl sulfate of 2-phenyl-10-methyl-2,3-dihydropyridazino [4,5-b] [1,4]benzothiazin-1,4(10H)-dione (A) and the corresponding 3-phenyl substituted isomer (B) has been studied. Some derivatives of (A) and (B) substituted at the O atom with dialkyaminoalkyl groups are described; these have been subjected to pharmacological testing.


Intermolecular proton transfer in solid phase: a rare example of crystal-to-crystal transformation from hydroxo- to oxo-bridged iron(III) molecule-based magnet.
Intermolecular proton transfer in solid phase from the hydroxo bridge to a water molecule occurs in a new mu-hydroxo iron(III) compound of formula {EtNH3[Fe2(ox)2Cl2(mu-OH)].2H2O}n leading to a still crystalline compound in which the mu-oxo bridge replaces the mu-hydroxo one. Both three-dimensional compounds exhibit magnetic ordering at Tc ca. 70 K due to a spin canting.


An overview of visual rehabilitation and training of the low vision patient.
The field of low vision requires a thorough understanding of the many psychologic considerations in visual rehabilitation as well as the current training procedures in the use of distance and near aids. This paper is an overview of these considerations with recommendations for the future.


Clinical update on the use of mesenchymal stem cells in COVID-19.
The COVID-19 pandemic has evoked the scientific community to combine all efforts needed to find a cure for the disease. With the limited therapeutic effects of pharmacological therapies, attention has been drawn to alternative ones such as stem-cell based therapy particularly with mesenchymal stem cells (MSCs). Recently, a large number of clinical trials are ongoing to evaluate the safety and efficacy of MSCs in patients with COVID-19; however, only very few data are released. Thereby, we anxiously await the results of FDA-approved trials to provide more definitive data on the use of MSCs in COVID-19 patients, especially the critically ill. Herein, we shed light on the therapeutic agents that have been tested and used for the treatment of COVID-19 and provide an insight into MSC-based approaches for COVID-19 at both preclinical and clinical levels.


Temporal trend and global burden of type 2 diabetes attributable to non-optimal temperature, 1990-2019: an analysis for the Global Burden of Disease Study 2019.
Exposure to hot or cold temperatures was reported to be associated with increased mortality and morbidity of type 2 diabetes, but few studies have estimated the temporal trend and global burden of type 2 diabetes attributable to non-optimal temperature. Based on the Global Burden of Disease Study 2019, we collected data on the numbers and rates of deaths and disability-adjusted life years (DALYs) of type 2 diabetes attributed to non-optimal temperature. The joinpoint regression analysis was used to estimate the temporal trends of the age-standardized rate of mortality and DALYs from 1990 to 2019 by average annual percentage change (AAPC). From 1990 to 2019, globally, the numbers of deaths and DALYs of type 2 diabetes attributable to non-optimal temperature increased by 136.13% (95% (uncertainty interval) UI: 87.04% to 277.76%) and 122.26% (95% UI: 68.77% to 275.59%), with the number from 0.05 (95% UI: 0.02 to 0.07) million and 0.96 (95% UI: 0.37 to 1.51) million in 1990 to 0. 11 (95% UI: 0.07 to 0.15) million and 2.14 (95% UI: 1.35 to 3.13) million in 2019. The age-standardized mortality rate (ASMR) and DALYs rate (ASDR) of type 2 diabetes attributable to non-optimal temperature showed an increasing trend in the high temperature effect and lower (low, low-middle and middle) socio-demographic index (SDI) region, with AAPCs of 3.17%, 1.24%, 1.61%, and 0.79% (all P < 0.05), respectively. The greatest increased ASMR and ASDR were observed in Central Asia, followed by Western Sub-Saharan Africa and South Asia. Meanwhile, the contribution of type 2 diabetes burden attributable to high temperature gradually increased globally and in five SDI regions. In addition, the global age-specific rate of mortality and DALYs of type 2 diabetes attributable to non-optimal temperature for both men and women almost increased with age in 2019. The global burden of type 2 diabetes attributable to non-optimal temperature increased from 1990 to 2019, particularly in high temperature, regions with lower SDI, and the older population. Appropriate temperature interventions are necessary to curb climate change and increasing diabetes.


Post-remediation geophysical assessment: Investigating long-term electrical geophysical signatures resulting from bioremediation at a chlorinated solvent contaminated site.
There is a growing need to assess long-term impacts of active remediation strategies on treated aquifers. A variety of biogeochemical alterations can result from interactions of the amendment with the aquifer, conceivably leading to a geophysical signal associated with the long-term alteration of an aquifer. This concept of post-remediation geophysical assessment was investigated in a shallow, chlorinated solvent-contaminated aquifer six to eight years after amendment delivery. Surface resistivity imaging and cross-borehole resistivity and induced polarization (IP) imaging were performed on a transect that spanned treated and untreated zones of the aquifer. Established relationships between IP parameters and surface electrical conductivity were used to predict vertical profiles of electrolytic conductivity and surface conductivity from the inverted cross-borehole images. Aqueous geochemistry data, along with natural gamma and magnetic susceptibility logs, were used to constrain the interpretation. The electrical conductivity structure determined from surface and borehole imaging was foremost controlled by the electrolytic conductivity of the interconnected pore space, being linearly related to fluid specific conductance. The electrolytic conductivity (and thus the conductivity images alone) did not discriminate between treated and untreated zones of the aquifer. In contrast, inverted phase angles and surface conductivities did discriminate between treated and untreated zones of the aquifer, with the treated zone being up to an order of magnitude more polarizable in places. Supporting aqueous chemistry and borehole logging datasets indicate that this geophysical signal from the long-term impact of the remediation on the aquifer is most likely associated with the formation of polarizable, dispersed iron sulfide minerals.


Identification of adolescent abuse and future intervention prospects.
Recent research indicates that the incidence rate for adolescent abuse equals or exceeds that of all other age groups. Because adolescent abuse is underreported to protective service agencies, it is less likely to be identified and served. Identifying adolescent abuse and understanding the dynamics of family interaction are important problems for researchers and service providers. Analysis of a sample of 62 two-parent families containing an adolescent highlights factors on the Adolescent Abuse Inventory (Sebes, 1983) and other characteristics of the family system and individuals which discriminated high-risk from low-risk family systems. The second part of the paper describes the procedures of an intervention project based on this classification system.


Central versus peripheral vision: evaluation of the residual function resulting from a uniocular macular scotoma.
This paper examines the contribution of the macular region to visual function. Several test targets were used to measure visual performance within 10 deg of the center of the fovea for normal observers and for an observer with a uniocular central 6-deg scotoma. We conclude that the nature of the test target is more important in the measurement of parafoveal than central vision and that the macular region contributes significantly to the visibility of objects as large as 2.5 deg.


Molecularly Imprinted Polymers for Cell Recognition.
Since their conception 50 years ago, molecularly imprinted polymers (MIPs) have seen extensive development both in terms of synthetic routes and applications. Cells are perhaps the most challenging target for molecular imprinting. Although early work was based almost entirely around microprinting methods, recent developments have shifted towards epitope imprinting to generate MIP nanoparticles (NPs). Simultaneously, the development of techniques such as solid phase MIP synthesis has solved many historic issues of MIP production. This review briefly describes various approaches used in cell imprinting with a focus on applications of the created materials in imaging, drug delivery, diagnostics, and tissue engineering.


Evaluation of the new API Candida system for identification of the most clinically important yeast species.
The API Candida system (bioMérieux) a new yeast identification system, was evaluated for its reliability in identifying 198 clinical yeast isolates in comparison with the API 20C system (bioMérieux) that was used as reference standard. The API Candida system correctly identified 91.4% and 71.7% of the isolates, with and without additional tests, respectively. The API Candida system identified 96.3% of common isolates studied, and 66.6% of uncommon isolates. We think that API Candida system is an easy and good yeast identification system and it could be used in a routine clinical microbiology laboratory.


STRUGGLING FOR FOOD IN A TIME OF CRISIS: A comment on Caplan (see pp 8-10 in this issue).
This commentary sets Caplan's arguments about food banks and food poverty in the broader context of changes to the welfare state, the 'charitization' of state welfare and the need to address food poverty within a framework of dignity rather than charity.


Application of the concept of 'therapeutic index' to surgery for stress incontinence.
The pharmacologic concept of therapeutic index can be applied to surgery for stress incontinence to obtain an objective prediction of surgical outcome. The rationale and mechanics of its application to surgery are discussed in this article. The conclusions support current clinical trends which favor discarding the anterior repair and needle suspension procedures as first-line surgical treatment of stress urinary incontinence in favor of the retropubic procedures. Suburethral sling procedures should be, as now, reserved for second-line surgical treatment of stress urinary incontinence.


A bioinformatics analysis of zinc finger protein family reveals potential oncogenic biomarkers in breast cancer.
Zinc finger protein family is the largest transcription factor family in the human genome. Studies have shown that the aberrant expression of zinc finger protein (ZNF) had a potential role in tumorigenesis. However, due to the high complexity of the ZNF family genes, the role of the ZNF family genes in breast cancer (BRCA) is still lacking in systematic understanding. In the study, we aim to understand the expression profile, prognostic value, immune invasion pattern, tumor microenvironment, epigenetic and pathway relationships, and drug sensitivity of ZNFs using multi-omics data from public databases. We focused on six members of ZNFs, which were upregulated in a variety of cancers. Notably, ZNF750 and ZNF224 were lower expressed in BRCA, and their expressions were significantly associated with BRCA prognosis. We confirmed the observations obtained by analyzing the clinic-pathological data. Otherwise, the expressions of ZNFs were significantly related to stromal and immune scores, and was significantly different among different immune subtypes in BRCA. Here, we found down-regulated methylation of ZNF217 and ZNF750. The relationship between methylation and survival showed the survival was worse for hypo-methylation of ZNF750 in BRCA, which is consistent with the correlation of high expression of ZNF750 in BRCA with worse survival. Collectively, our results provide clues for a better understanding of the characterization of ZNF family genes in BRCA from a multi-omics perspective and show their potential for use as new tumor markers and therapeutic targets.


Knowledge of dietary supplement label information among female supplement users.
The use of dietary supplements is a popular form of health behavior, especially among women. Little research has been conducted to determine consumers' comprehension of supplement label information. Therefore, this research evaluated comprehension of supplement label information among women 25-45 years of age who consumed a dietary supplement > or =4 times per week. Participants (n=51) completed a written questionnaire about supplement practices, a 10-item knowledge test, and an individual interview about terms used on supplement labels. Participants answered 70% of the questions correctly on the knowledge test indicating adequate knowledge of dietary sources of nutrients. Knowledge of recommended dosages, dosing instructions, and instructions about inappropriate use of supplements for certain people also was adequate. However, misconceptions regarding the term "natural" on supplement labels, product claims, and testing for product safety existed among participants. Supplement users need additional education about supplement claims and testing for product safety and efficacy to make informed health care choices.


The large majority of coeliacs have a high degree of perceived dietary competence.
Purpose: The treatment for coeliac disease (CD) is a gluten-free diet (GFD), which impacts the health-related quality of life (HRQoL). The aim of the study was to develop the Gluten-Free Diet Perceived Competence Scale (GFD-PCS): a short and precise CD-specific patient-reported outcome measure.Methods: The GFD-PCS was developed from the scales 'Perceived Competence (Maintaining a Healthy Diet)' and 'Perceived Competence for Diabetes'. The scale was then programmed into a web-based questionnaire and distributed together with generic quality of life (WHO-5) and CD-specific HRQoL (CDQL) questionnaires.Results: There were 931 respondents. The 831 who reported 'diagnosed CD' were retained. The average age was 37.6 years (SD = 16.5). There was no statistically significant difference between males (M = 5.9, SD = 1.6) and females (M = 6.2, SD = 1.4) in GFD-PCS score. Respondents younger than 18 years (n = 104) scored lower (M = 5.8, SD = 1.4) than adults (M = 6.2, SD = 1.4). The psychometric properties of the GFD-PCS showed excellent internal reliability (α = .96) and satisfied construct and criterion validity.Conclusion: The GFD-PCS measures patient-perceived dietary competence for maintaining a GFD. The scale is psychometrically robust and provides a useful tool in assessing patients' difficulties with a GFD.


Spruce budworm growth, development and food utilization on young and old balsam fir trees.
Laboratory rearing of spruce budworm, Choristoneura fumiferana, in conjunction with field rearing, gravimetric analyses, a transfer experiment, and foliage chemical analyses at six dates during the period of budworm feeding activity indicated that the age of balsam fir, Abies balsamea, trees (70-year-old mature trees or 30-year-old juvenile trees) affected tree suitability for the spruce budworm via the chemical profile of the foliage. Insects reared on old trees had greater survival and pupal weight, shorter development times, and caused more defoliation than those reared on young trees. Young trees were more suitable for the development of young larvae (instars 2-5), while old trees were more suitable for the development of older, sixth-instar larvae. These results were confirmed by the laboratory transfer experiment. Young larvae fed foliage from young trees had higher relative growth rates (RGR), digestibility (AD), and efficiency of conversion of ingested foliage (ECI) than those fed foliage from old trees. These differences appeared to be related to the high N:tannins ratio, and the high contents of P present in young trees during the development of the young larvae. Old larvae fed foliage from old trees had higher relative growth rates, relative consumption rates (RCR), and digestibility of the foliage than those fed foliage from young trees. The high digestibility of the foliage of old trees was compensated for by a lower efficiency of conversion of digested food (ECD), which in turn resulted in no significant effect of tree age on the efficiency of conversion of ingested foliage by old larvae. The low relative consumption rate of old larvae fed foliage from young trees appeared to be related to the low N:tannins ratio, and the high contents of bornyl acetate, terpinolene, and °-3-carene present in young trees during the budworm sixth instar. Variations in these compounds in relation to tree age may serve as mechanisms of balsam fir resistance to spruce budworm by reducing the feeding rate of sixth instar larvae.


Association between alcohol consumption and metabolic syndrome among Korean adults: nondrinker versus lifetime abstainer as a reference group.
Discrepant results regarding the association between alcohol consumption and metabolic syndrome may be partly attributable to the different selection of the reference group. Data from a representative sample of 6,432 Korean adults in 2008 were analyzed. Using lifetime abstainers as the reference group, the prevalence of metabolic syndrome among men was increased in ex-drinkers [3.15 (1.69-5.89)], responsible drinking [0.1-39.9 g/day; 1.77 (1.0-3.13)], and hazardous drinking [≥40 g/day; 2.06 (1.05-4.07)]. Alcohol consumption in men, but not in women, is associated with a higher prevalence of metabolic syndrome.


Evaluation of the MRSA-Screen Test in detecting oxacillin resistance in community and hospital isolates of Staphylococcus aureus.
The MRSA-Screen Test (Denka Seiken Co., Japan), a latex agglutination test to detect penicillin-binding protein 2a, was compared with PCR for the detection of oxacillin resistance in Staphylococcus aureus. A total of 77 oxacillin-sensitive and 269 oxacillin-resistant (ORSA) isolates were evaluated. Of the ORSA isolates, 186 were non-multiresistant (NORSA), defined as being resistant to two or fewer antibiotics other than beta-lactams. Eighty-three were multiresistant ORSA (MORSA) strains. If PCR is considered the gold standard test, then the sensitivity, specificity, positive and negative predictive values of the MRSA-Screen Test were 100, 99, 99 and 100%, respectively. The endpoint was hard to read with NORSA strains that took longer than 60 s to react. MORSA strains took a median 12 s (range 5-60 s) to give a positive reaction with the MRSA-Screen Test, whereas NORSA strains took a median 30 s (range 5-180 s), a difference which was significantly different (P < 0.0001, two-tailed Mann-Whitney unpaired two sample test). NORSA strains had an MIC50 of 128 mg/l and MIC90 of 256mg/l, whereas MORSA strains had an MIC50 and MIC90 of >256mg/l. The time that the MRSA-Screen Test took to agglutinate with ORSA strains correlated weakly with the MIC (r2 = 0.26). Detection of methicillin resistance cost AUD$9 per isolate with the MRSA-Screen Test, compared with AUD$13 per isolate with mecA PCR. The MRSA-Screen Test gave excellent sensitivity and specificity, and was quicker and cheaper than PCR. The full 3 min should be allowed to elapse before calling a test negative. Organisms giving indeterminate reactions should be tested for the mecA gene by PCR.


Superiority of [68Ga]Ga-FAPI-04/[18F]FAPI-42 PET/CT to [18F]FDG PET/CT in delineating the primary tumor and peritoneal metastasis in initial gastric cancer.
This study aimed to compare [68Ga]Ga-FAPI-04/[18F]FAPI-42 PET/CT with [18F]FDG PET/CT in the evaluation of initial gastric cancer. We retrospectively compared [68Ga]Ga-FAPI-04/[18F]FAPI-42 PET/CT with [18F]FDG PET/CT in patients with initial gastric cancer from September 2020 to March 2021. Lesion detectability and the uptake of lesions quantified by the maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR) were compared between the two modalities using the Wilcoxon signed-rank test, Mann-Whitney U test, and McNemar's chi-square test. A total of 61 patients (37 males, aged 23-81 years) were included, of which 22 underwent radical gastrectomy. For primary lesions, higher uptake of [68Ga]Ga-FAPI-04/[18F]FAPI-42 was observed compared to [18F]FDG (median SUVmax, 14.60 vs 4.35, p < 0.001), resulting in higher positive detection using [68Ga]Ga-FAPI-04/[18F]FAPI-42 PET/CT than [18F]FDG PET/CT (95.1% vs 73.8%, p < 0.001), particularly for tumors with signet-ring cell carcinoma (SRCC) (96.4% vs 57.1%, p < 0.001). [68Ga]Ga-FAPI-04/[18F]FAPI-42 PET/CT detected more positive lymph nodes than [18F]FDG PET/CT (637 vs 407). However, both modalities underestimated N staging compared to pathological N staging. [68Ga]Ga-FAPI-04/[18F]FAPI-42 PET/CT showed a higher sensitivity (92.3% vs 53.8%, p = 0.002) and peritoneal cancer index score (18 vs 3, p < 0.001) in peritoneum metastasis and other suspect metastases compared to [18F]FDG PET/CT. Our findings indicate that [68Ga]Ga-FAPI-04/[18F]FAPI-42 PET/CT outperformed [18F]FDG PET/CT in the evaluation of primary tumors with SRCC and peritoneum metastasis in initial gastric cancer. However, no clinically useful improvement was seen in N staging. • The uptake of [68Ga]Ga-FAPI-04/[18F]FAPI-42 in primary tumor and metastasis was intensely higher than that of [18F]FDG (p < 0.001) in 61 patients with initial gastric cancer. • [68Ga]Ga-FAPI-04/[18F]FAPI-42 PET/CT had a higher sensitivity detection in primary tumors (95.1% vs 73.8%, p < 0.001) and peritoneal metastases (92.3% vs 53.8%, p = 0.002) than [18F]FDG PET/CT. • [68Ga]Ga-FAPI-04/[18F]FAPI-42 PET/CT depicted more positive lymph nodes than [18F]FDG PET/CT (637 vs 407); however, both underestimated N staging compared to pathological N staging.


Endoscopic radiofrequency ablation plus plastic stent placement versus stent placement alone for unresectable extrahepatic biliary cancer: a multicenter randomized controlled trial.
We sought to compare the efficacy and safety between endoscopic radiofrequency ablation (RFA) and stent placement alone in patients with unresectable extrahepatic biliary cancer (EBC). In this randomized controlled trial, patients with locally advanced or metastatic cholangiocarcinoma (CCA) or ampullary cancer who were unsuitable for surgery were recruited from 3 tertiary centers. Eligible patients were randomly assigned to RFA plus plastic stent placement (RFA group) or plastic stent placement alone (stent placement alone group) in a 1:1 ratio. Both groups underwent 2 scheduled interventions with an interval of approximately 3 months. The primary outcome was overall survival (OS). Altogether, 174 participants completed the 2 index endoscopic interventions. No significant differences in baseline characteristics were noted between the 2 groups. The median OS was significantly higher in the RFA group (14.3 vs 9.2 months; hazard ratio, .488; 95% confidence interval, .351-.678; P < .001). A survival benefit was also shown in patients with CCA (13.3 vs 9.2 months; hazard ratio, .546; 95% confidence interval, .386-.771; P < .001). However, no significant between-group differences were found in jaundice control or stent patency duration. The postprocedural Karnofsky performance scores were significantly higher in the RFA group until 9 months (all P < .001). Adverse events were comparable between the 2 groups (27.6% vs 19.5%, P = .211), except for acute cholecystitis, which was more frequently observed in the RFA group (9 vs 0, P = .003). Compared with stent placement alone, additional RFA may improve OS and quality of life of patients with inoperable primary EBC who do not undergo systemic treatments. (Clinical trial registration number: NCT01844245.).


Weight control practices of severely obese patients who are not seeking bariatric surgery.
We sought to better understand why so few severely obese patients undergo bariatric surgery in the United States. We conducted a telephone survey to assess the weight control practices of severely obese patients who were not actively seeking bariatric surgery in Group Health, a health system in Washington State. Among 295 severely obese participants surveyed (63% response rate), most reported actively working on weight loss (58%), although current use of commercial weight loss programs (10%) and obesity pharmacotherapy (0.1%) was low. Household income and white race were strongly associated with lifetime use of commercial programs, suggesting a possible disparity in use of effective treatment for obesity. Many were interested in learning more about bariatric surgery (49%) and pharmacotherapy (53%), but few had ever discussed surgery (26%) or pharmacotherapy (33%) with their physician. Finally, although only 29% had coverage for bariatric surgery, those with coverage were not more likely to have discussed bariatric surgery with their physician. Overall, our survey of severely obese patients who are not currently seeking bariatric surgery suggests that interest in obesity treatments is high, coverage and receipt of treatment is low, and that there is a potential socioeconomic disparity related to the use of commercial programs.


The sampling and determination of halocarbons in ambient air using concentration on porous polymer.
The levels of halocarbons have been determined in rural air in central Michigan using a sampling procedure employing pre-concentration on a porous polymer. The samples were analyzed by gas chromatography (GC) with an electron capture detector. Both qualitative and quantitative confirmation of the results were achieved by GC-mass spectrometry. Trichlorofluoromethane, chloroform, 1,1,1-trichloroethane, carbon tetrachloride, trichloroethylene and perchloroethylene were determined in the range of 30-130 parts per trillion. These concentrations agree well with data obtained by others in Washington state and Ireland indicating even distribution of the halocarbons in these latitudes.


Noninvasive Endodontic Periapical Biopsy of a Periapical Fibrous Scar: Case Report.
Postendodontic periapical fibrous scars (PFScs) comprise a type of radiolucent healing that is frequently misinterpreted as a pathological lesion. A combined clinical, radiologic, and histologic correlation is essential for a reliable diagnosis. This report presents a case of a patient with a long-term persistent asymptomatic postendodontic radiolucency that was misdiagnosed as endodontic failure and referred for endodontic retreatment and periapical surgery. To reach a definitive diagnosis, a core bone biopsy needle (CBBn) technique was performed on the area of the radiolucency. The material obtained was processed for histologic analysis and the lesion was determined to be a PFSc. In conclusion, the use of a CBBn before any invasive treatment allowed the clinician to distinguish between PFSc and other persisting pathosis, such as periapical granuloma or cystic lesions.


Photosynthetic microorganisms for the oxygenation of advanced 3D bioprinted tissues.
3D bioprinting technology has emerged as a tool that promises to revolutionize the biomedical field, including tissue engineering and regeneration. Despite major technological advancements, several challenges remain to be solved before 3D bioprinted tissues could be fully translated from the bench to the bedside. As oxygen plays a key role in aerobic metabolism, which allows energy production in the mitochondria; as a consequence, the lack of tissue oxygenation is one of the main limitations of current bioprinted tissues and organs. In order to improve tissue oxygenation, recent approaches have been established for a broad range of clinical applications, with some already applied using 3D bioprinting technologies. Among them, the incorporation of photosynthetic microorganisms, such as microalgae and cyanobacteria, is a promising approach that has been recently explored to generate chimerical plant-animal tissues where, upon light exposure, oxygen can be produced and released in a localized and controlled manner. This review will briefly summarize the state-of-the-art approaches to improve tissue oxygenation, as well as studies describing the use of photosynthetic microorganisms in 3D bioprinting technologies. STATEMENT OF SIGNIFICANCE: 3D bioprinting technology has emerged as a tool for the generation of viable and functional tissues for direct in vitro and in vivo applications, including disease modeling, drug discovery and regenerative medicine. Despite the latest advancements in this field, suboptimal oxygen delivery to cells before, during and after the bioprinting process limits their viability within 3D bioprinted tissues. This review article first highlights state-of-the-art approaches used to improve oxygen delivery in bioengineered tissues to overcome this challenge. Then, it focuses on the emerging roles played by photosynthetic organisms as novel biomaterials for bioink generation. Finally, it provides considerations around current challenges and novel potential opportunities for their use in bioinks, by comparing latest published studies using algae for 3D bioprinting.


From eye to arrow: Attention capture by direct gaze requires more than just the eyes.
Human attention is strongly attracted by direct gaze and sudden onset motion. The sudden direct-gaze effect refers to the processing advantage for targets appearing on peripheral faces that suddenly establish eye contact. Here, we investigate the necessity of social information for attention capture by (sudden onset) ostensive cues. Six experiments involving 204 participants applied (1) naturalistic faces, (2) arrows, (3) schematic eyes, (4) naturalistic eyes, or schematic facial configurations (5) without or (6) with head turn to an attention-capture paradigm. Trials started with two stimuli oriented towards the observer and two stimuli pointing into the periphery. Simultaneous to target presentation, one direct stimulus changed to averted and one averted stimulus changed to direct, yielding a 2 × 2 factorial design with direction and motion cues being absent or present. We replicated the (sudden) direct-gaze effect for photographic faces, but found no corresponding effects in Experiments 2-6. Hence, a holistic and socially meaningful facial context seems vital for attention capture by direct gaze. STATEMENT OF SIGNIFICANCE: The present study highlights the significance of context information for social attention. Our findings demonstrate that the direct-gaze effect, that is, the prioritization of direct gaze over averted gaze, critically relies on the presentation of a meaningful holistic and naturalistic facial context. This pattern of results is evidence in favor of early effects of surrounding social information on attention capture by direct gaze.


Isolation, identification and characterization of a Peste des Petits Ruminants virus from an outbreak in Nanakpur, India.
A Peste des Petits Ruminants virus (PPRV) was isolated from an outbreak that occurred in sheep and goats in Nanakpur village of Mathura District in Uttar Pradesh (India). Based on hemagglutination of chicken red blood cells (rbcs), cytopathic effect similar to that caused by the Morbilliviruses in Vero cells, and amplification and sequence analysis of the viral nucleoprotein (N) gene, the identity of the virus was confirmed as PPRV and named PPRV/C. hircus-tc/India/2012/Nanakpur1 (in short PPRV/Nkp1/2012). However, based on its poor neutralization with monoclonal antibodies, escape detection by commercial ELISA, and unsuccessful amplification of the hemagglutinin (H) and the fusion (F) genes by several pairs of published PCR primers it was concluded that the PPRV/Nkp1/2012 may not be closely related to lineage type IV PPR viruses believed to be present in the Indian subcontinent. A plaque assay for titration of the PPRV was developed for the first time. The virus was plaque purified and its growth characteristics were studied in the African green monkey kidney (Vero) cells and baby hamster kidney (BHK-21) cells. In a one-step growth curve analysis it was concluded that the duration of the PPRV life cycle is 6-8h, an uncharacterized part of PPRV replication. These findings provide information for devising control strategies against PPR in India by choosing a homologous candidate vaccine prototype.


Systematic Evaluation of Optical Coherence Tomography Angiography in Retinal Vein Occlusion.
To evaluate the clinical utility of optical coherence tomography angiography (OCTA) in patients with retinal vein occlusion (RVO), and to systematically compare OCTA images with changes seen on color fundus photography and fluorescein angiography (FA). Reliability analysis. Eighty-one eyes of 76 patients with a history of RVO (branch, central, or hemicentral), both acute and chronic, underwent OCTA and color fundus photography. In 29 eyes, data were compared to FA imaging. Comparative and multimodal analysis of the 3 imaging procedures were performed. We identified good agreement between FA and OCTA scans centered on the macula for capillary nonperfusion (intraclass correlation coefficient [ICC] 0.825 for the 3 × 3-mm scan and 0.891 for the 8 × 8-mm scan). Agreement for area of capillary changes (dilation, pruning, and telangiectasia) was also substantial (ICC 0.712 for the 3 × 3-mm scan and 0.787 for the 8 × 8-mm scan). For foveal avascular zone grading, agreement was good for the 3 × 3-mm scan (kappa = 1.000 for radius and kappa = 0.799 for outline) but poor for the 8 × 8-mm scan (kappa = 0.156 for radius and kappa = 0.600 for outline). The quality of the images obtained was an important issue for OCTA, as 15.1% of scans were nongradable, particularly in patients unable to maintain fixation. OCTA is a quick, reliable, and noninvasive method to evaluate the area of capillary nonperfusion and foveal avascular zone morphology in patients with RVO. However, good fixation is a requirement for acquisition of good-quality images.


The pharmacokinetics and organ distribution of ajmaline and quindine in the mouse.
After i.v. infusion into mice (lasting 10 s) the time courses of ajmaline and quinidine concentrations in blood, heart, lung, liver, and brain were studied. The drugs were assayed by a spectrofluorophotometric procedure. Blood concentration data obtained were fitted graphically and calculations were performed in accordance with an open two compartment model. Blood kinetic data were very similar for both alkaloids. A rapid distribution phase with a t0.5alpha of 3.0 min for ajmaline and 2.5 min for quindine was followed by a disposition phase with a t0.5beta of 16 min for ajmaline and 20 min for quinidine. High tissue accumulation of both alkaloids was found in lung, liver, and heart and this is also reflected by the volume of distribution Vdbeta, which was 136 ml for ajmaline and 116 ml for quinidine (body weight of the mice = 31 g). With equilibrium dialysis a 62% binding of ajmaline and a 77% binding of quinidine to mouse blood constituents was found. Both drugs were highly metabolized since only 5% of a given dose was excreted unchanged in the urine.


Improvement of sodium status to optimize the efficacy of Renin-Angiotensin system blockade.
Blockade of the renin-angiotensin-aldosterone system (RAAS) offers superior renoprotection in the treatment of patients with hypertension, but the efficacy of RAAS inhibition strongly depends on sodium status, presumably in relation to extracellular volume status. Because assessing volume status by physical examination is challenging, 24-hour urine collection and NT-proBNP levels are useful tools for guiding volume management and achieving sodium status targets.


Gas-phase and PM2.5-bound phthalates in nail salons: characteristics, exposure via inhalation, and influencing factors.
This study aimed to investigate the characteristics of, exposure to, and factors influencing gas-phase and PM2.5-bound phthalates (PAEs) in nail salons. Data on both indoor and outdoor gas-phase and PM2.5-bound PAEs, carbon dioxide (CO2), temperature, and relative humidity were collected in nail salons. We also used questionnaires to survey building characteristics and occupants' behaviors. The average total gas-phase and PM2.5-bound PAE concentrations indoors were higher than those outdoors by 6 and 3 times, respectively. Diethyl phthalate, diisobutyl phthalate (DiBP), di-n-butyl phthalate (DnBP), and di-(2-ethylhexyl) phthalate (DEHP) were the predominant compounds among both the gas-phase and PM2.5-bound PAEs in indoor air. The volume of the salon's space or the difference of indoor and outdoor CO2 concentrations (dCO2) was significantly associated with indoor PAE concentrations. The ratios of PM2.5-bound to gas-phase PAEs, especially high-molecular-weight PAEs, were positively associated with the dCO2 concentrations. Higher ratios of indoor to outdoor PM2.5-bound DiBP, DnBP, and DEHP concentrations were discovered when more clients visited each day. Building characteristics, ventilation conditions, and occupants' activities have influences on the gas-phase and particle-phase PAEs. The study identifies the characteristics of gas-phase and PM2.5-bound PAEs in nail salons and their influencing factors.


Electroresection with a new endotracheally applicable resectoscope.
Besides dilatation, cryotherapy, laser and surgical resection, the technique of endoscopic, endotracheal electroresection provides an alternative in the treatment of endotracheal stenoses. The instrument is similar to the resectoscope used in urology, but additionally equipped with a longer action range and respiration facility. It is insulated at the tip of the shaft. The electroresectoscope was employed on 64 occasions at our institution in three indications: endotracheal diseases, granulomas following tracheostomy; and short subglottic membrane stenoses, partly secondary to long-term intubation. Indications, advantages and drawbacks of the method are discussed.


Epikarst water detection using integrated geophysical methods.
When detecting epikarst water using the self-potential method, the actual location of the anomaly center often deviates from the prospecting result due to the interference of the regional background field, which is comprised of geological noise and artificial electromagnetic fields. Ultimately, this makes it difficult to locate the detection target accurately. To address the potential offset of the anomaly center location, in this study we introduce the differential filtering method into the data processing procedure. This method has smoothing and low-pass filtering effects, facilitating the extraction of meaningful anomalies. Meanwhile, based on the anomalous features of different physical parameters, we propose an integrated method system based on differentially filtered horizontal self-potential gradient data, the composite profile method, and the high-density electrical method, which can effectively improve the accuracy of anomaly localization. This newly established method system was applied at the Xiaguantun test site in Longzhou County, Chongzuo, Guangxi Province, China, and its effectiveness and feasibility was confirmed.


Treatment Algorithm and Clinical Outcome of Venous Malformations of the Limbs.
Venous malformations of the limbs are congenital low-flow vascular anomalies. A treatment is reasonable if they are symptomatic or if a progressive lesion may affect functional structures. The purpose of this work is the presentation of clinical results after treatment of venous malformations of the limbs according to the standard algorithm used at the University Hospital of Tuebingen, Germany. Between January 2008 and June 2015, patients with venous malformations of the limbs were subjected to either percutaneous sclerotherapy or surgical excision according to this treatment algorithm. Remaining symptoms such as pain level and disturbing appearance before and after treatment as well as overall satisfaction was assessed the earliest 3 months after last treatment. Thirty-nine patients with venous malformations of the limbs were subjected to either 1 or more percutaneous sclerotherapies (n = 19) or surgical excision (n = 21). There were no serious complications that needed surgical revision. There was a statistically significant reduction in the pain level and disturbing appearance after both sclerotherapy and surgical excision (p < .05) in 30 cases in total. The overall treatment satisfaction was rated 7.9/10 and 8.8/10 after sclerotherapy and surgical excision, respectively. A low complication rate with a high patient satisfaction could be achieved after this treatment algorithm for venous malformations of the limbs.


Chemical peels.
Chemical peels are important tools for skin rejuvenation. Their popularity is related to their versatility and relative simplicity. Chemical peels are classified as superficial, medium, and deep according to the depth of penetration of the peeling solution. The results of the procedure depend on the chemical used and its concentration, method of application, contact time, skin condition, preparation, etc. The depth of the peel determines the patient's inconvenience during and after the procedure, healing time, the rate of the potential side effects, and the results. In this article, we discuss the basic methods for skin peeling, the variety of chemicals used, the potential side effects, and how to avoid them.


The impact of increased chest compression fraction on survival for out-of-hospital cardiac arrest patients with a non-shockable initial rhythm.
We evaluated the effect of chest compression fraction (CCF) on survival to hospital discharge and return of spontaneous circulation (ROSC) in out-of-hospital cardiac arrest (OHCA) patients with non-shockable rhythms. This is a retrospective analysis (completed in 2016) of a prospective cohort study which included OHCA patients from ten U.S. and Canadian sites (Resuscitation Outcomes Consortium Epistry and PRIMED study (2007-2011)). We included all OHCA victims of presumed cardiac aetiology, not witnessed by emergency medical services (EMS), without automated external defibrillator shock prior to EMS arrival, receiving > 1 min of CPR with CPR process measures available, and initial non-shockable rhythm. We measured CCF using the first 5 min of electronic CPR records. Demographics of 12,928 adult patients were: mean age 68; male 59.9%; public location 8.5%; bystander witnessed 35.2%; bystander CPR 39.3%; median interval from 911 to defibrillator turned on 10 min:04 s; initial rhythm asystole 64.8%, PEA 26.0%, other non-shockable 9.2%; compression rate 80-120/min (69.1%); median CCF 74%; ROSC 25.6%; survival to hospital discharge 2.4%. Adjusted odds ratio (OR); 95% confidence intervals (95%CI) of survival for each CCF category were: 0-40% (2.00; 1.16, 3.32); 41-60% (0.83; 0.54, 1.24); 61-80% (1.02; 0.77, 1.35); and 81-100% (reference group). Adjusted (OR; 95%CI) of ROSC for each CCF category were: 0-40% (1.02; 0.79, 1.30); 41-60% (0.83; 0.72, 0.95); 61-80% (0.85; 0.77, 0.94); and 81-100% (reference group). We observed an incremental benefit from higher CCF on the incidence of ROSC, but not survival, among non-shockable OHCA patients with CCF higher than 40%.


Fluorescence monitoring of the conformational change in alpha 2-macroglobulin induced by trypsin under second-order conditions: the macroglobulin acts both as a substrate and a competitive inhibitor of the protease.
The reaction of bovine pancreatic trypsin with human plasma alpha(2)-macroglobulin (alpha(2)M) was studied at 25 degrees C, using equimolar mixtures of E and I in 50 mM potassium phosphate buffer, pH 7. The conformational change in alpha(2)M was monitored through the increase in protein fluorescence at 320 nm (exc lambda, 280 nm). At [alpha(2)M](0) =[E](0) =11.5-200 nM, the fluorescence change data fit the integrated second-order rate equation, (F(infinity) -F(0) )/(F(infinity) -F(t) )=1+k(i,obsd) [alpha(2)M](0) t, indicating that cleavage of the bait region in alpha(2)M was the rate-determining step. The apparent rate constant (k(i,obsd)) was found to be inversely related to reactant concentration. The kinetic behavior of the system was compatible with a model involving reversible, nonbait region binding of E to alpha(2)M, competitively limiting the concentration of E available for bait region cleavage. The intrinsic value of k(i) was (1.7+/-0.24) x 10(7) M(-1) s(-1).K(p), the inhibitory constant associated with peripheral binding, was estimated to be in the submicromolar range. The results of the present study point to a potential problem in interpreting kinetic data relating to protease-induced structural changes in macromolecular substrates. If there is nonproductive binding, as in the case of trypsin and alpha(2)M, and the reactions are monitored under pseudo first-order conditions ([S](0) >>[E](0) ), an intrinsically second-order process (such as the rate-limiting bait region cleavage in alpha(2)M) may become kinetically indistinguishable from an intrinsically first-order process (e.g. rate-limiting conformational change). Hence an excess of one component over the other should be avoided in kinetic studies addressing such systems.


Acute variceal bleeding: pharmacological treatment and primary/secondary prophylaxis.
Variceal bleeding is one of the most severe complications of portal hypertension related to liver cirrhosis. Primary prophylaxis is considered mandatory in patients with cirrhosis and high-risk oesophageal varices, and once varices have bled, every effort should be made to arrest the haemorrhage and prevent further bleeding episodes. In acute variceal bleeding, vasoactive drugs that lower portal pressure should be started even before endoscopy, and should be maintained for up to 5 days. The choice of vasoactive drug should be made according to local resources. Terlipressin, somatostatin and octreotide can be used; vasopressin plus transdermal nitroglycerin may be used if no other drug is available. In variceal bleeding, antibiotic therapy is also mandatory. In primary and secondary prophylaxis, beta-blockers are the mainstay of therapy. In secondary prophylaxis (but not in primary prophylaxis) these drugs can be combined with organic nitrates.


[Detection of eosinophil cationic protein and E-selectin in serum and nasal lavage fluid in patients with allergic rhinitis].
To evaluate the role of eosinophil cationic protein (ECP) and serum soluble E-selectin (sE-selectin) in patients with allergic rhinitis. The sE-selectin were detected from 30 allergic patients and 20 normal individuals by enzyme-linked immunosorbent assay (ELISA). The ECP in serum and nasal lavage fluid was assayed with pharmacia CAP system. The level of sE-selectin in patients with allergic rhinitis was(41.846 +/- 12.21) ng/ml, higher than that in control (10.678 +/- 2.458) ng/ml. The level of ECP in serum and nasal lavage fluid from patients with allergic rhinitis was significantly higher than that from normal controls. The level of ECP in nasal lavage fluid was much higher than that in serum. ECP and sE-selectin play a role in pathogenesis of allergic rhinitis.


Single quantum dot controls a plasmonic cavity's scattering and anisotropy.
Plasmonic cavities represent a promising platform for controlling light-matter interaction due to their exceptionally small mode volume and high density of photonic states. Using plasmonic cavities for enhancing light's coupling to individual two-level systems, such as single semiconductor quantum dots (QD), is particularly desirable for exploring cavity quantum electrodynamic (QED) effects and using them in quantum information applications. The lack of experimental progress in this area is in part due to the difficulty of precisely placing a QD within nanometers of the plasmonic cavity. Here, we study the simplest plasmonic cavity in the form of a spherical metallic nanoparticle (MNP). By controllably positioning a semiconductor QD in the close proximity of the MNP cavity via atomic force microscope (AFM) manipulation, the scattering spectrum of the MNP is dramatically modified due to Fano interference between the classical plasmonic resonance of the MNP and the quantized exciton resonance in the QD. Moreover, our experiment demonstrates that a single two-level system can render a spherical MNP strongly anisotropic. These findings represent an important step toward realizing quantum plasmonic devices.


Analysis of the Drosophila betaPS subunit indicates that regulation of integrin activity is a primal function of the C8-C9 loop.
Integrin-ligand interactions can be influenced by the sequence in a disulfide-bridged loop between the 8th and 9th beta subunit cysteines. Previous experiments are consistent with C8-C9 loop residues being involved in direct ligand-integrin interactions and/or being important in heterodimer regulation. In betaPS from Drosophila melanogaster and three other dipterans, the C8-C9 loop consists of only two amino acids, and exists in two forms that arise by differential splicing of exon 4. In these species, the betaPS4A isoform has an acidic residue in the first loop position (C8+1), with an alanine or proline in the corresponding position of betaPS4B. Mutations in both isoforms (in combination with alphaPS2) can reduce cell spreading during normal growth, but function is generally restored under conditions that enhance integrin activation. Replacement of the betaPS4A acidic residue with a basic lysine has relatively modest effects on integrin function. Spread cells bearing C8-C9 mutations tend to become less elongated, with reduced frequencies of actin stress fibers. The results indicate that even a minimal, two-residue C8-C9 loop contains structural information that can differentially regulate integrin activity and/or integrin signaling, and that this regulation does not rely on direct molecular interactions involving the variable C8+1 side chains.


[The prospects for studying the induced genetic instability unber the spaceflight conditions].
Consideration is given to the facts of mutagenesis during orbital space flight and tangibility of development for and application of genetic tests to space crewmembers based on the present-day concepts about the cellular mechanisms of genome maintenance and destabilization.


"I was never like that": Australian findings on the psychological and psychiatric sequelae of corticosteroids in haematology treatments.
Corticosteroid treatments have been well documented to cause severe emotional and even psychiatric disturbances. Despite that corticosteroid use is at the core of most treatment protocols for haematological malignancies, there is a dearth of published research (and controversy in the existing research) on the emotional and psychiatric sequelae of corticosteroid use for haematology patients and its connection with pre-existing mental history. This paper aims to address this hiatus and confusion by examining the emotional and psychiatric side effects of corticosteroids on haematology patients in Australia. The findings are from a pilot study that explored the prior mental health history and effects of corticosteroid use of ten haematology patients in Australia. Data was collected through an iterative, phenomenological, qualitative research methodology using open-ended interviews conducted at the time and location of the participant's choice. The interviews were audio-recorded and transcribed verbatim. The language texts were then entered into the QSR NUD*IST computer program and analysed thematically. The significant finding from the study was that corticosteroids used in haematology treatments have the potential to affect anyone and are not related to an individual's prior mental health history. No participant presented evidence of psychiatric history or counseling and many reported emotional stability during previous times of difficulty. All participants reported emotional distress directly related to corticosteroid use. Participants reported difficulties during the period of withdrawal from corticosteroids and relief during periods free from the administration of corticosteroids. The findings provide evidence that emotional disturbances associated with corticosteroid use in haematology are a direct result of the drugs used and not a symptom of the individual's prior emotional health. Recommendations are given which have important implications for the management, support and education of patients and their families in relation to the potential emotional side effects from steroid administration and withdrawal.


Recycling of phosphate tailings for an efficient hydroxyapatite-based adsorbent to immobilize heavy metal cations.
Hydroxyapatite (HAP) is a promising adsorbent for immobilizing heavy metals in soil and water. However, the preparation and modification of HAP from pure chemicals increases its cost and limits its large-scale practical application. In this study, a hydroxyapatite-based adsorbent (HAPPT) was prepared from phosphate tailing produced in the phosphorus industry to sequester Pb, Cd and Zn from solution. The results showed that HAPPT was composed of HAP and MgO, with a surface area of 27.74 m2/g. The kinetics studies showed that most Pb and Cd were removed from the initial solution in 4 h and the adsorption of Zn increased with increasing contact time. Metals presented higher adsorption capacities at 35 °C than that at 25 °C. The adsorption isotherms showed that HAPPT presented high adsorption capacities for Pb, Cd and Zn in mono-metal solutions. The adsorption capacity of Cd at pH 6 was higher than that at pH 3, but the adsorption for Pb and Zn was similar at both pHs. HAPPT has selectivity for Pb in Pb-Cd-Zn multi-metals solution, and competitive adsorption reduced the adsorption quantity by 53%, 93% and 79% for Pb, Cd and Zn, respectively. The combined results of TEM-EDS, XRD and XPS showed that Pb was immobilized by forming phosphates due to the dissolution of HAP, whereas Cd and Zn were immobilized by forming hydroxide precipitates resulting from the function of MgO in HAPPT. The results of this study provided an efficient adsorbent for the removal of heavy metals in solution and provided a new perspective on the recycling of phosphate tailings in the phosphorus industry.


Computerized home telemetry of maternal blood pressure in hypertensive pregnancy.
We have developed a telemetric technique whereby maternal blood pressure, which is self-measured by pregnant women in their own homes using a Dinamap 1846 automated blood pressure recorder, can then be transmitted over the commercial telephone network into the Rosie Maternity Hospital in Cambridge, where it is computer-processed. The maternal blood pressure is then reviewed by the obstetrician as part of the clinical management protocol. We have used this telemetric technique on 90 occasions, from the homes of 10 pregnant hypertensive women. On almost every occasion, the blood pressure measured at home was lower than that previously measured in the hospital antenatal clinic. This technique offers great promise, both in terms of health economics and also in terms of reducing pregnant women's unhappiness about their being admitted to hospital whenever they exhibit moderate to severe hypertension in the antenatal clinic. Indeed, in the antenatal period, home telemetry should allow the vast majority of hypertensive pregnancies to be managed just as safely at home as in hospital. In the management of high risk pregnancy, home telemetry of maternal blood pressure complements three other home telemetric techniques which have already been described: fetal heart rate, maternal blood glucose and uterine contractions.


Anticonvulsant effects of ivermectin on pentylenetetrazole- and maximal electroshock-induced seizures in mice: the role of GABAergic system and KATP channels.
Ivermectin (IVM) is an antiparasitic medicine that exerts its function through glutamate-gated chloride channels and GABAA receptors predominantly. There is paucity of information on anti-seizure activity of IVM. Moreover, the probable pharmacological mechanisms underlying this phenomenon have not been identified. In this study, pentylenetetrazole (PTZ)-induced clonic seizures and maximal electroshock (MES)-induced tonic-clonic seizure models, respectively in mice was utilized to inquire whether IVM could alter clonic seizure threshold (CST) and seizure susceptibility. To assess the underlying mechanism behind the anti-seizure activity of IVM, we used positive and negative allosteric modulators of GABAA (diazepam and flumazenil, respectively) as well as KATP channel opener and closer (cromakalim and glibenclamide, respectively). Data are provided as mean ± S.E.M. After the performance of the variance homogeneity test, a one-way and two-way analysis of variance was used. Fisher's exact test was performed in case of MES. P-value less than 0.05 considered statistically significant. and Discussion: Our data showed that IVM (0.5, 1, 5, and 10 mg/kg, i.p.) increased CST. Furthermore, flumazenil 0.25 mg/kg, i.p. and glibenclamide 1 mg/kg, i.p., could inhibit the anticonvulsant effects of IVM. Supplementary, an ineffective dose of diazepam 0.02 mg/kg, i.p. or cromakalim 10 μg/kg, i.p. were able to enhance the anticonvulsant effects of IVM. Besides, we figure out that the IVM (1 and 5 mg/kg, i.p.) could delay the onset of first clonic seizure and also might decrease the frequency of clonic seizures induced by PTZ (85 mg/kg, i.p.). Finally, IVM could prevent the incidence and death in MES-induced tonic-clonic seizures. Based on the obtained results, it can be concluded that IVM may exert anticonvulsant effects against PTZ- and MES-induced seizures in mice that might be mediated by GABAA receptors and KATP channels.


Neural bases of action abstraction.
There has been recent debate over whether actions are processed primarily by means of motor simulation or cognitive semantics. The current study investigated how abstract action concepts are processed in the brain, independent of the format in which they are presented. Eighteen healthy adult participants viewed different actions (e.g., diving, boxing) in the form of verbs and schematic action pictograms while functional magnetic resonance imaging (fMRI) was collected. We predicted that sensorimotor and semantic brain regions would show similar patterns of neural activity for different instances of the same action (e.g., diving pictogram and the word 'diving'). A representational similarity analysis revealed posterior temporal and sensorimotor regions where specific action concepts were encoded, independent of the format of presentation. These results reveal the neural instantiations of abstract action concepts, and demonstrate that both sensorimotor and semantic systems are involved in processing actions.


Nuclear localisation of nuclear factor-kappaB transcription factors in prostate cancer: an immunohistochemical study.
Several reports suggest that the canonical nuclear factor-kappaB (NF-kappaB) pathway is constitutively activated in a subset of prostate cancer cells. However, except for RelA (p65), little is known about the status of NF-kappaB transcription factors in prostate cancer tissues. To clarify the status of NF-kappaB subunits, we analysed the expression and subcellular localisation of RelA, RelB, c-Rel, p50, and p52 on tissue array sections containing respectively 344, 346, 369, 343, and 344 cores from 75 patients. The subcellular localisation of NF-kappaB factors was tested against relevant clinical parameters (preoperative prostate-specific antigen, pathological stage, and postoperative Gleason grade). With the exception of c-Rel, each subunit was detected in the nucleus of cancer cells: significant nuclear expression of RelB, RelA, p52, and p50 was seen in 26.6, 15.6, 10.7, and 10.5% of cores, respectively. Surprisingly, cores expressing both nuclear RelA and p50 canonical pathway proteins were less frequently observed than cores expressing other subunit combinations such as RelB-p52 and RelA-RelB. In addition, the nuclear localisation of RelB correlated with patient's Gleason scores (Spearman correlation: 0.167; P=0.018). The nuclear localisation of both canonical and noncanonical NF-kappaB subunits in prostate cancer cells suggests for the first time that different NF-kappaB pathways and dimers may be activated in the progression of the disease.


Injury of the common peroneal nerve after cardiothoracic operations.
To assess incidence, etiology, and clinical relevance of common peroneal nerve injury (CPNI) in patients after cardiothoracic surgery. In an 11-year period, CPNI was detected in 39 out of 20,718 patients (0.19%): 38 times after cardiopulmonary bypass (CPB) (38 of 12,726; 0.30%) and in 1 patient after a non-CPB procedure (1 of 7,992; 0.013%). These patients underwent intensive physiotherapeutic treatment. As the majority of CPNI occurred after CPB (97.4%), data of these patients were compared with a 1-year set of 1,032 patients who underwent CPB procedures. Patients with CPNI were older, had a higher percentage of subnormal body weight, and had considerable comorbidity such as peripheral arteriosclerotic disease, diabetes mellitus, and arrhythmias. Follow-up was complete (mean: 5.2 years; 0.4 to 10.7 years). Twenty-eight patients were free of symptoms; 10 patients complained of moderate symptoms, but were not limited in their everyday life; 1 patient still suffers from severe sensorimotor symptoms. CPNI after cardiothoracic surgery is rare. Duration of the operative procedure, an increased comorbidity, and a subnormal body weight are assumed to have an etiologic impact. Prognosis is mostly good, but early physiotherapeutic treatment is crucial for prognosis.


Rhegmatogenous retinal detachment after prophylactic argon laser photocoagulation.
In our hospital, 62 retinal detachments (RDs) in 58 patients who had previously been subjected to prophylactic argon laser photocoagulation (ALP), were operated on between July 1980 and October 1985. The incidence of RDs after prophylactic ALP has increased in recent years, being 3.90% (10 out of 256 RDs) in 1982, and 12.09% (26 out of 215 RDs) in 1985. The time interval between ALP and the occurrence of RD was less than 1 year in 54.7% of the patients, and between 1 and more than 10 years in 45.3%. Fifty per cent of the RDs developed after prophylactic ALP of retinal breaks. Fifty per cent of the RDs occurred after prophylactic treatment of degenerative lesions of the peripheral retina; 77% of the RDs in this last group occurred in eyes that had been subjected to 360 degrees photocoagulation. From the data obtained from the present series, the value of the 360 degrees technique for prophylactic ALP would appear to be rather questionable in most cases. In the present series, most RDs occurring after prophylactic ALP did not appear to be less severe than RDs in eyes that had not been subjected to prophylactic treatment.


Retracted: Efficacy and Safety of Amniotic Membrane Transplantation Combined with Closure of Tenon Capsule and Bulbar Conjunctival Space in the Treatment of Primary Pterygium.
[This retracts the article DOI: 10.1155/2022/5844973.].


Systemic administration of naloxone produces analgesia in BALB/c mice in the formalin pain test.
Systemic administration of naloxone usually produces either hyperalgesia or no change in nociception depending on the animal species used and/or the pain test employed. This study, however, demonstrates that naloxone produces a dose-dependent analgesia in the formalin pain test using an inbred strain of albino mouse. Female BALB/c, C57BL/6 and CD1 mice were injected subcutaneously with naloxone HCl in saline (0.1 10.0 mg/kg) or saline alone, and tested for analgesia using the formalin test. Naloxone produced a statistically significant dose-dependent analgesia in the BALB/c mice, with an ED50 of 0.24 mg/kg and almost total analgesia at doses of 1 mg/kg or greater. No changes in pain behaviour were observed in the C57BL/6 or CD1 strains of mice. We believe this to be the first report of analgesia following administration of doses of naloxone normally used for opioid antagonism. To determine if this effect was specific to the formalin test, the 3 strains of mice were injected subcutaneously with naloxone HCl and tested in the tail-flick test. Naloxone had no analgesic action in this test in any of the strains.


Cytochrome c3 from the sulfate-reducing anaerobe Desulfovibrio africanus Benghazi: antigenic properties.
Antisera were prepared against cytochromes c3 from Desulfovibrio africanus, D. vulgaris, and D. salexigens. Cross-reactions were observed between antisera to D. vulgaris and D. africanus cytochromes and heterologous cytochromes c3. A weak cross-reaction with antisera against both D. vulgaris and D. africanus cytochromes and the acid form of the D. salexigens cytochrome was seen; the basic form did not react.


Hand-held Dopplers in central catheter insertion.
Peripherally inserted central catheters benefit many patients requiring repeated intravenous treatment. This study investigated the effect of using a hand-held Doppler to aid insertion where a patient's veins are not visible or palpable.


Dissociated invasively growing cancer cells with NF-kappaB/p65 positivity after radiotherapy: a new marker for worse clinical outcome in rectal cancer? Preliminary data.
Objectives Nuclear factor-kappaB (NF-kappaB), especially p65 subunit, seems to be associated with origin and progression of cancer. The aim of the study was to determine expression of NF-kappaB/p65 in rectal cancer patients before and after radiotherapy as well as to assess the relationship between NF-kappaB/p65 expression, other tumor characteristics, and disease progression. Further aim was to evaluate whether expression of NF-kappaB/p65 in tumor tissue may serve as a predictive marker of patient outcome. Patients and methods Twenty-five patients with rectal cancer undergoing pre-operative radiotherapy were included in the study. Unirradiated rectal cancer specimens were obtained from diagnostic colonoscopy. Irradiated rectal cancer specimens were obtained from surgically removed part of the rectum with the tumor. NF-kappaB/p65 expression was determined by immunohistochemistry. Results Cytoplasmic positivity in cancer cells and nuclear positivity in lymphocytes were detected. In post-radiotherapy specimens single tumor cells or small clones of them deeply infiltrating the wall of the rectum, that were characterized by high NF-kappaB/p65 expression, were found. Patients with presence of these cells in post-radiotherapy specimens have worse clinical outcome in terms of overall survival and disease-free interval. Conclusion While the NF-kappaB/p65 positive staining of the epithelial cells did not have any clinical implications in this study, it may be of clinical significance in the future. Residual invasively growing cancer cells with high NF-kappaB/p65 positivity found in specimens after radiotherapy and surgery may be used to find what patients have a worse outcome. Thus, patients being at risk of cancer progression and requiring more aggressive anti-cancer therapy may be identified.


Form and dimensions of aggregates dictate cytotoxicities of Danish dementia peptides.
Familial Danish dementia (FDD) is a neurodegenerative disease which results due to alterations in the BRI2 gene. The pathological symptoms of the disease are cerebral amyloidolysis, parenchymal protein deposits and neuronal degeneration. The ADan peptide is a 34 amino acid long peptide which is thought to be the major cause of amyloid deposition in brains of patients suffering from FDD. Due to the presence of two cysteine residues viz. cys5 and cys23, this peptide exists in two forms: a cyclic oxidized form where the two cysteines form a disulfide bridge and a linear reduced form where the sulphydryl groups of cysteine are free. The relationship between toxicity and structure of the reduced and oxidized forms of ADan peptides has been elucidated by a combination of biophysical and cellular toxicity assays. It is observed that the reduced peptide has a stronger lethal effect on neuronal cell lines compared to its oxidized counterparts at all stages of aggregation. Further, it is observed that the fresh reduced peptide induced greater cell death as compared to its aged counterpart.


Infant sleep and negative reactivity: The role of maternal adversity and perinatal sleep.
Sleep during infancy contributes to the development and maintenance of infant regulatory functioning and may be an early risk marker for more difficult temperamental traits like negative reactivity. Further, maternal adverse childhood experiences (ACEs) may predispose individuals to greater sleep disturbances in adulthood and have been linked with sleep disturbances in both mothers and infants. Thus, examining maternal history of ACEs and maternal sleep difficulties during pregnancy and postpartum may provide insight into underlying risk factors affecting infant sleep difficulties and early temperament development. Fifty-nine mothers from a diverse, community sample (44% white) completed questionnaires on ACEs, maternal sleep, infant sleep, and infant temperament at 30-weeks gestation, 6-weeks postpartum, and 16-weeks postpartum. Results indicated that maternal ACES and sleep problems during pregnancy have long term implications for infant negative reactivity at 16-weeks, with significant indirect effects through maternal and infant sleep problems at 6-weeks. Addressing psychosocial functioning and prenatal sleep during pregnancy, particularly among women with high ACEs, may be a target of intervention to improve maternal and infant sleep health during the postpartum, and reduce the risk for difficult infant temperament.


Protein kinase clk/STY is differentially regulated during erythroleukemia cell differentiation: a bias toward the skipped splice variant characterizes postcommitment stages.
Clk/STY is a LAMMER protein kinase capable to phosphorylate serine/arginine-rich (SR) proteins that modulate pre-mRNA splicing. Clk/STY alternative splicing generates transcripts encoding a full-length kinase and a truncated catalytically inactive protein. Here we showed that clk/STY, as well as other members of the family (e.g. clk2, clk3 and clk4), are up-regulated during HMBA-induced erythroleukemia cell differentiation. mRNAs coding for the full-length and the truncated forms were responsible for the overall increased expression. In clk/STY, however, a switch was observed for the ratio of the two alternative spliced products. In undifferentiated cells the full-length transcript was more abundant whereas the transcript encoding for the truncated form predominated at latter stages of differentiation. Surprisingly, overexpression of clk/STY did not alter the splicing switch upon differentiation in MEL cells. These results suggest that clk/STY might contribute to control erythroid differentiation by a mechanism that implicates a balance between these two isoforms.


Online-Learning due to COVID-19 Improved Mental Health Among Medical Students.
In reference to the announcement of the pandemic of the new coronavirus 2019-(nCoV), all educational institutions in the Republic of Kazakhstan have switched to online learning (OL). The purpose of this study was to investigate the mental state of the medical students switching to OL in comparison with the mental state of the students who had traditional learning (TL). A repeated questionnaire-based cross-sectional study was conducted among medical students ranging from 1st year to 5th year at Astana Medical University in the 2019-2020 academic year. The first study was conducted during the TL (October-November 2019, N = 619), and the second study was conducted during the OL period (April 2020, N = 798). Burnout syndrome, depression, anxiety, somatic symptoms, and satisfaction with academic performance have been studied. The findings revealed that prevalence of the burnout syndrome, depression, anxiety, and somatic symptoms decreased after transitioning from TL to OL. However, during the OL period, the prevalence of colleague-related burnout increased, which tells us about the negative impact of OL on students' communication and interpersonal relationships. The most common depression and anxiety symptoms, dissatisfaction with academic performance were among students who indicated a decrease in academic performance during OL. Students who lived alone during the quarantine were more prone to depression during OL. In conclusion, during the quarantine period after the transition from TL to OL, the mental health state of medical students improved, despite the severe conditions of the pandemic. The online version contains supplementary material available at 10.1007/s40670-020-01165-y.


Epidemiology, clinical and physiological manifestations of dust lung disease in major industrial centers.
The present study aims to determine the structure of morbidity in workers contacting industrial aerosols, assess the timeliness of diagnosing dust-induced lung disease in major industrial centers, and optimize diagnostics for early detection of occupational lung diseases in workers exposed to industrial dust hazards. The study on the structure and incidence of occupational lung diseases was carried out in 2016-2020 based on the Moscow Centre for Occupational Pathology data. For a more in-depth clinical examination, 114 patients who were first admitted to the Occupational Pathology Centre with diagnosed pneumoconiosis (PC), chronic dust-induced bronchitis (CDB), and chronic obstructive pulmonary disease (COPD) were selected. All patients were subjected to a complex clinical-functional, spirographic, echocardiographic, fibroscopic, radiological, and CT lung examination, with subsequent analysis of the results obtained. The pathology caused by exposure to industrial aerosols within the studied period was first diagnosed in 344 workers. Most patients (64%) with newly detected pathologies were 50-59 years of age, with work experience in adverse conditions of 21-25 years (41%). The spirographic study of respiratory function revealed decreased forced vital capacity (FVC) indices in CDB and COPD patients. Changes in expiratory flow rates suggest occupational bronchitis at an earlier stage, whereas no apparent results were noted for the PC diagnosis. The results of fibroscopic examination in PC patients revealed atrophic processes of the bronchial mucosa in 46 (88.5%) of them, and 6 (11.5%) patients had a subtropic process. The results of echocardiographic examination allowed diagnosing pulmonary heart disease in 83 patients (72.8%). Of them, 42 (80.8%) were revealed in the group of patients with PC, 18 (50.0%) in the COB group, and 14 (53.8%) in the COPD group. Computed tomography (CT) detected pathological changes in 52 patients, while the X-ray examination in six people showed no evidence of lung destruction. CT scan also showed that the number of patients with fibrotic PC (including silicosis) in the study groups increased. Timely clinical and functional examination (spirography, fibroscopy, echocardiography) of patients allows detecting PC (including silicosis), CDB, and COPD at an early stage of disease progression.


Three molecular steps of aminoglycoside ototoxicity demonstrated in outer hair cells.
Previously postulated molecular mechanisms of aminoglycoside ototoxicity were investigated in outer hair cells in vitro. Cells were isolated by microdissection from the organ of Corti of the guinea pig and maintained in Hank's balanced salt solution. (1) Approx. 100 cells (the standard number per assay) bound 432 +/- 198 pmol calcium as determined with 45Ca2+ (1.2 mM). 1 mM neomycin or gentamicin lowered this value by 28% and 45%, respectively. (2) Binding of radiolabeled gentamicin (28 fmol per 100 cells at 0.1 microM gentamicin) was reduced by 55% by 1 mM neomycin or spermine. Washing with an excess of unlabeled gentamicin displaced only 60% of the drug, the remainder being tightly bound to a less accessible compartment. Incubation at low temperature essentially abolished gentamicin uptake. (3) Phospholipids were labeled with [32P]orthophosphate which was mostly incorporated into phosphatidylinositol 4,5-bisphosphate (PIP2), phosphatidylinositol 4-phosphate, phosphatidylinositol, and phosphatidic acid. When the lipids were chromatographed over immobilized gentamicin PIP2, in contrast to other lipids, was strongly retained. These results are compatible with the following actions of aminoglycosides in outer hair cells: (1) competition with calcium; (2) energy-dependent uptake competitive with polyamines; and (3) binding to the phospholipid PIP2.


Intrinsic markers of tumour hypoxia and angiogenesis in localised prostate cancer and outcome of radical treatment: a retrospective analysis of two randomised radiotherapy trials and one surgical cohort study.
Expression of intrinsic markers of tumour hypoxia and angiogenesis are important predictors of radiotherapeutic, and possibly surgical, outcome in several cancers. Extent of tumour hypoxia in localised prostate cancer is comparable to that in other cancers, but few data exist on the association of extent of tumour hypoxia with treatment outcome. We aimed to study the predictive value of intrinsic markers of tumour hypoxia and angiogenesis in localised prostate cancer, both in patients treated with radiotherapy and in those treated surgically. We applied a new, needle biopsy tissue microarray (TMA) technique to study diagnostic samples from men with localised, previously untreated prostate cancer treated in two randomised controlled trials of radiotherapy-dose escalation. Multivariate analysis by Cox proportional hazards was done to assess the association between clinical outcome, in terms of biochemical control, and immunohistochemical staining of hypoxia inducible factor-1 alpha (HIF-1 alpha), vascular endothelial growth factor (VEGF), and osteopontin expression. The analysis was repeated on an independent series of men with localised, previously untreated prostate cancer treated by radical prostatectomy. The main outcome was time to biochemical (ie, prostate-specific antigen [PSA]) failure. Between Oct 12, 1995, and Feb 5, 2002, 308 patients were identified from two prospective, randomised trials at the Royal Marsden Hospital, London and Sutton, UK, for the radiotherapy cohort and diagnostic biopsies were available for 201 of these patients. Between June 6, 1995, and Nov 4, 2005, 329 patients were identified from the Aarhus University Hospital, Skejby, Denmark, for the prostatectomy cohort; of these, 40 patients were excluded because the tumour was too small to sample (19 patients), because the paraffin block was too thin (19 patients), or because the blocks were missing (two patients), leaving 289 patients for analysis. For patients treated with radiotherapy, increased staining for VEGF (p=0.008) and HIF-1 alpha (p=0.02) expression, but not increased osteopontin expression (p=0.978), were significant predictors of a shorter time to biochemical failure on multivariate analysis, independent of clinical tumour stage, Gleason score, serum PSA concentration, and dose of radiotherapy. For patients treated with surgery, increased staining for VEGF (p<0.0001) and HIF-1 alpha (p<0.0001) expression, and increased osteopontin expression (p=0.0005) were each significantly associated with a shorter time to biochemical failure on multivariate analysis, independent of pathological tumour stage, Gleason score, serum PSA concentration, and margin status. To our knowledge, this is the largest study of intrinsic markers of hypoxia and angiogenesis in relation to the outcome of radical treatment of localised prostate cancer. Increased expression of VEGF, HIF-1 alpha, and, for patients treated with surgery, osteopontin, identifies patients at high risk of biochemical failure who would be suitable for enrolment into trials of treatment intensification.


Docking proteins and peptides under evolutionary constraints in Critical Assessment of PRediction of Interactions rounds 38 to 45.
Computational structural prediction of macromolecular interactions is a fundamental tool toward the global understanding of cellular processes. The Critical Assessment of PRediction of Interactions (CAPRI) community-wide experiment provides excellent opportunities for blind testing computational docking methods and includes original targets, thus widening the range of docking applications. Our participation in CAPRI rounds 38 to 45 enabled us to expand the way we include evolutionary information in structural predictions beyond our standard free docking InterEvDock pipeline. InterEvDock integrates a coarse-grained potential that accounts for interface coevolution based on joint multiple sequence alignments of two protein partners (co-alignments). However, even though such co-alignments could be built for none of the CAPRI targets in rounds 38 to 45, including host-pathogen and protein-oligosaccharide complexes and a redesigned interface, we identified multiple strategies that can be used to incorporate evolutionary constraints, which helped us to identify the most likely macromolecular binding modes. These strategies include template-based modeling where only local adjustments should be applied when query-template sequence identity is above 30% and larger perturbations are needed below this threshold; covariation-based structure prediction for individual protein partners; and the identification of evolutionarily conserved and structurally recurrent anchoring interface motifs. Overall, we submitted correct predictions among the top 5 models for 12 out of 19 interface challenges, including four High- and five Medium-quality predictions. Our top 20 models included correct predictions for three out of the five targets we missed in the top 5, including two targets for which misleading biological data led us to downgrade correct free docking models.


Algorithm for employing physical forces in metabolic bone diseases.
Metabolic bone diseases, especially osteoporosis, demand a multidisciplinary approach. The physical forces find a rationale in the treatment of local alterations in bone-cartilage metabolism. In integrated treatment of vertebral fractures caused by fragility, stimulation with electrical fields has been observed to be effective in reducing pain and improving patients' quality of life.


Major complications after tongue-tie release: A case report and systematic review.
The diagnosis of ankyloglossia, or tongue-tie, and the number of frenotomies performed has increased over 10-fold from 1997 to 2012 in the United States. The sharpest increase has been in neonates. For parents considering frenotomy for their breastfeeding newborn, there is controversy surrounding the evaluation of tongue-tie and the benefit of a frenotomy. Complications from tongue-tie procedures are thought to be low, though it is not well reported nor studied. The aim of this study is to describe a case of a sublingual mucocele after laser frenotomy in a neonate with tongue-tie and to investigate major complications reported after tongue-tie release in pediatric patients through a systematic review of the literature. We present a 6-week-old female who underwent a laser frenotomy procedure performed by a dentist who presented with a new cyst under her tongue. A systematic literature search of articles published from 1965 to April 2020 was conducted in Ovid MEDLINE(R), Ovid EMBASE, and Scopus. Citations were uploaded into a systematic review software program (DistillerSR, Ottawa, ON, Canada), followed by full text screening. 47 major complications were reported in 34 patients, including our patient. Most of the cases were located in the United States and Europe. The most frequent indications for the procedure were breastfeeding problems (n = 18) and speech impediment (n = 4). The procedure was performed by dentists (n = 6), lactation consultants (n = 5), and otolaryngologists (n = 4). The bulk of the major complications after frenotomy included poor feeding (n = 7), hypovolemic shock (n = 4), apnea (n = 4), acute airway obstruction (n = 4), and Ludwig angina (n = 2). Reporting of complications after frenotomy is lacking. Risks to neonates may be different than risks to older children and adults. Practitioners across different specialties should be monitoring and studying this more rigorously to better guide patients and families on the risks and benefits of this procedure.