Does the Academy of Breastfeeding Medicine's Clinical Protocol #36 'The Mastitis Spectrum' promote overtreatment and risk worsened outcomes for breastfeeding families? Commentary.
In 2022 the Academy of Breastfeeding Medicine (ABM) published Clinical Protocol #36: The Mastitis Spectrum, which aims to update clinical approaches to management of benign lactation-related breast inflammation. The protocol has been timely because of the exponential increase in knowledge about the human milk microbiome over the past decade. This Commentary aims to continue respectful debate amongst clinicians and researchers within the Academy of Breastfeeding Medicine and more broadly, confident that we share a fundamental commitment to promote breastfeeding and support the well-being of lactating women, their infants and their families. Although Clinical Protocol #36 offers advances, it does not fulfil the principles of best practice implementation science for translation of evidence into clinical guidelines. Clinical Protocol #36 inaccurately represents studies; misrepresents theoretical models as proven aetiologies; does not consistently attribute sources; does not reliably apply the SORT taxonomy; and relies upon single case reports. As a result, various recommendations in Clinical Protocol #36 lack an evidence-base or credible underlying theoretical model. This includes recommendations to use 'lymphatic drainage' massage, therapeutic ultrasound, and oral lecithin. Similarly, based on a contestable theoretical model which is presented as fact, Clinical Protocol #36 makes the recommendation to either reduce frequency of milk removal or to maintain current frequency of milk removal during an episode of breast inflammation. Although Clinical Protocol #36 limits this advice to cases of 'hyperlactation', the diagnosis 'hyperlactation' itself is undefinable. As a result, this recommendation may put breastfeeding women who present with breast inflammation at risk of worsened inflammation and decreased breast milk production. Clinical Protocol #36 offers some advances in the management of breast inflammation. However, Clinical Protocol #36 also exposes clinicians to two international trends in healthcare which undermine health system sustainability: overdiagnosis, including by over-definition, which increases risk of overtreatment; and antibiotic over-use, which worsens the crisis of global antimicrobial resistance. Clinical Protocol #36 also recommends unnecessary or ineffective interventions which may be accessed by affluent patients within advanced economies but are difficult to access for the global majority. The Academy of Breastfeeding Medicine may benefit from a review of processes for development of Clinical Protocols.


Development of a rapid, one-step-visual method to detect Salmonella based on IC-LAMP method.
Salmonella can cause serious human gastroenteritis and is frequently isolated from various food samples. The cell culturing, immunoassay, and polymerase chain reactions (PCR) are the current methods to detect such pathogenic agents. However, these methods are time-consuming and labor-intensive, and thus unavailable for rapid-monitoring of Salmonella. This study aimed to develop an immunocapture-loop-mediated isothermal amplification (IC-LAMP) for rapid and sensitive detection of Salmonella. Salmonella was used as antigen to produce monoclonal antibody (mAb) and mAbs were prepared via subcloning three times. The mAb 1B12 with high affinity was coated on the surface of the immuno-magnetic beads (IMBs) to capture Salmonella. The enriched products (IMBs-Salmonella) were used for LAMP using the special primers targeted the conserved invA gene of Salmonella. The IC-LAMP was developed based on mAb 1B12 and LAMP. Targeting the conserved invA gene of Salmonella, the detection time was shortened to 50 min from three days. If the reaction contains Salmonella, the green fluorescence and the trapezoidal strip can be clearly observed. Importantly, the method combines the specificity of antibody and LAMP with a detection limit of 5 CFU/ml in artificially contaminated water and milk. The specificity of this method was demonstrated by testing other similar bacteria. The results indicate that the IC-LAMP reacts only with Salmonella and does not cross-react with other similar bacteria. The IC-LAMP assay developed here is a rapid, sensitive, one-step-visual method to screen for the presence of Salmonella in food samples. This method is faster than traditional PCR, LAMP, and other methods, and can be used as a primary screening method for the detection.


Orthopaedic Device Approval Through the Premarket Approval Process: A Financial Feasibility Analysis for a Single Center.
The 2 main routes of medical device approval through the U.S. Food and Drug Administration are the premarket approval (PMA) process, which requires clinical trials, and the 510(k) premarket notification, which exempts devices from clinical trials if they are substantially equivalent to an existing device. Recently, there has been growing concern regarding the safety of devices approved through the 510(k) premarket notification. The PMA process decreases the potential for device recall; however, it is substantially more costly and time-consuming. Investors and medical device companies are only willing to invest in devices if they can expect to recoup their investment within a timeline of roughly 7 years. Our study utilizes financial modeling to assess the financial feasibility of approving various orthopaedic medical devices through the 510(k) and PMA processes. The expected time to recoup investment through the 510(k) process ranged from 0.585 years to 7.715 years, with an average time of 2.4 years; the expected time to recoup investment through the PMA route ranged from 2.9 years to 24.5 years, with an average time of 8.5 years. Six of the 13 orthopaedic device systems that we analyzed would require longer than our 7-year benchmark to recoup the investment costs of the PMA process. With the 510(k) premarket notification, only 1 device system would take longer than 7 years to recoup its investment costs. Although the 510(k) premarket notification has demonstrated safety concerns, broad requirements for PMA authorization may limit device innovation for less-prevalent orthopaedic conditions. As a result, new approval frameworks may be beneficial. Our report demonstrates how current regulatory policies can potentially influence orthopaedic device innovation.


Procedures for precise measurements of 135Cs/137Cs atom ratios in environmental samples at extreme dynamic ranges and ultra-trace levels by thermal ionization mass spectrometry.
Determination of 135Cs/137Cs atom ratios has the potential to be a powerful tool for nuclear forensics and monitoring environmental processes. We present optimized chemical separation techniques and thermal ionization mass spectrometry (TIMS) protocols to obtain precise 135Cs/137Cs atom ratios for a range of environmental sample types. We use a combination of double AMP-PAN separation and Sr-spec resin column purification to yield excellent separation from the alkali metals (Rb separation factor > 600), which normally suppress ionization of Cs. A range of emission activators for the ionization of Cs were evaluated and glucose solution yielded the optimal combination of a stable Cs+ beam, minimal low-temperature polyatomic interferences and improved ionization efficiency. Mass-spectrometric determination of low abundance 135Cs and 137Cs is compromised by the presence of a very large 133Cs+ beam, which may be scattered and cause significant spectral interferences. These are explored using multi-static Faraday cup - ion counter methods and a range of energy filter settings. The method is evaluated using environmental samples and standards from regions affected by fallout from Chernobyl (IAEA-330) and Fukushima nuclear disasters. Where the intensity of 133Cs+ is large relative to 135Cs+ and 137Cs+ (< 30cps), minor polyatomic interferences need to be considered. In the absence of a standard with 135, 137Cs/133Cs < 1 × 10-8, we explored the reproducibility of 135Cs/137Cs atom ratios at these high dynamic ranges and extremely low abundance (137Cs ≈ 12 fg g-1) for sediments from an estuarine setting in SW England, UK.


Ethical problems in research on risky behaviors and risky populations.
The articles by Brooks-Gunn, Fisher, Hoagwood, Liss and Scott-Jones (all in this issue) present a panoply of real-world ethical issues in conducting scientific research on risky behaviors of children, adolescents, and their parents, particularly those from vulnerable populations. The universal, ethical principles of beneficence, justice, and respect for others are always applicable, but they do not resolve issues of child assent, parental consent, legal reporting requirements for illegal behaviors, and the special problems of studying risky behaviors in risky populations. Taken as a group, the articles raise some of the most interesting ethical problems that arise in developmental research. My discussion elaborates some issues and fails to resolve others. I hold the view that both science and ethics can be served by thoughtfully designed and implemented research on important social issues, but that the studies themselves cannot simultaneously solve the many societal problems of participants and be scientifically credible.


Development and Validation of a Novel Indicator of Visual Disability in the National Health and Aging Trends Study.
The National Health and Aging Trends Study (NHATS) is an ongoing, nationally representative panel study of older adults that collects data on health and disability, including measures on self-reported visual disability (SRVD). Prior studies assessing the association of SRVD with other measures of healthy aging have classified participants as having or not having SRVD, which does not capture the full spectrum of SRVD reported by participants. Therefore, we sought to develop and validate an ordinal indicator of SRVD to facilitate research on the impact of late-life SRVD on health and disability in NHATS. We used 2015 NHATS data with community-dwelling participants who answered survey questions about visual functioning and vision aid use. Based on responses, participants were categorized into one of 6 groups: blind, near and distance SRVD without vision aid use, near and distance SRVD with vision aid use, near or distance SRVD without vision aid use, near or distance SRVD with vision aid use, or no SRVD. Multivariable Poisson regression models assessed convergent validity of the ordinal SRVD scale with functional activity and well-being scores, while adjusting for demographic factors and medical comorbidities. Of the 7061 eligible individuals, 8.3% (n = 742) reported SRVD. Using our novel ordinal indicator of SRVD in NHATS, higher levels of SRVD were significantly associated with lower functional activity scores (p < .001 for all) and subjective well-being (p < .001), except for participants reporting blindness. Significant differences between SRVD groups were found, which could not be captured using a binary SRVD variable. A novel 6-level SRVD scale in NHATS demonstrated convergent validity with functional activity and well-being scales. This scale provides a new tool with improved measurement precision to study the impact of late-life SRVD on health and disability in a nationally representative study of older adults.


Intestinal Failure-Associated Liver Disease and Growth Pre- and Post-Transition to a Composite Lipid Emulsion.
Infants with intestinal failure have an increased risk of intestinal failure-associated liver disease (IFALD). Composite intravenous lipid emulsion (ILE) may reduce the risk of cholestasis. The primary outcome was to compare IFALD rates in infants with intestinal failure, between those receiving a composite ILE versus soybean oil ILE. The secondary outcome compared growth between these 2 groups. At our 2 tertiary neonatal/pediatric hospitals, we identified all patients (≤1 year old) who received ≥6 weeks parenteral nutrition (PN) from 2010 to 2018. Data included liver and growth parameters. IFALD was defined as serum conjugated bilirubin (CB) >33 µmol/L (≥2 mg/dL). Nonparametric tests were used for all comparisons. Fifty infants (35 composite ILE, 15 soybean oil ILE) were included. Those on composite ILE received PN for longer (10.1 vs 7.6 weeks; P = 0.001) and had higher baseline CB (29 vs 6.5 μmol/L; P = 0.001). No differences were found by 6 weeks (14.5 vs 5 μmol/L; P = 0.54) and by PN cessation (4 vs 4 μmol/L; P = 0.33). The proportion of patients with IFALD decreased from 54% to 20% for composite ILE, while stable given soybean oil ILE (7%). There were no differences in weight, length, or head circumference z scores ( P > 0.05). In our institutions, over 8 years, chronic intestinal failure was rare. Composite ILE was the predominant lipid choice for infants who needed longer courses of PN or had developed cholestasis. Despite longer PN duration, and higher baseline CB, overall rates of IFALD decreased with composite ILE. Regardless of parenteral lipid used, there were no differences in growth.


Calmodulin-like proteins from Arabidopsis and tomato are involved in host defense against Pseudomonas syringae pv. tomato.
Complex signal transduction pathways underlie the myriad plant responses to attack by pathogens. Ca(2+) is a universal second messenger in eukaryotes that modulates various signal transduction pathways through stimulus-specific changes in its intracellular concentration. Ca(2+)-binding proteins such as calmodulin (CaM) detect Ca(2+) signals and regulate downstream targets as part of a coordinated cellular response to a given stimulus. Here we report the characterization of a tomato gene (APR134) encoding a CaM-related protein that is induced in disease-resistant leaves in response to attack by Pseudomonas syringae pv. tomato. We show that suppression of APR134 gene expression in tomato (Solanum lycopersicum), using virus-induced gene silencing (VIGS), compromises the plant's immune response. We isolated APR134-like genes from Arabidopsis, termed CML42 and CML43, to investigate whether they serve a functionally similar role. Gene expression analysis revealed that CML43 is rapidly induced in disease-resistant Arabidopsis leaves following inoculation with Pseudomonas syringae pv. tomato. Overexpression of CML43 in Arabidopsis accelerated the hypersensitive response. Recombinant APR134, CML42, and CML43 proteins all bind Ca(2+ )in vitro. Collectively, our data support a role for CML43, and APR134 as important mediators of Ca(2+)-dependent signals during the plant immune response to bacterial pathogens.


[Six cases of petroclival meningiomas with main tumor site of the free tentorial rim--so-called tentorium notch meningiomas].
Petroclival meningiomas especially petroclival meningiomas with prevalent expansion to the tentorial notch are extreme rare. In the present paper we report about six patients with petroclival meningiomas of the tentorial notch who were operated in four years. The particular anatomical relations and the resulting symptoms and the neurosurgical procedures are discussed in detail. The postoperative state of the six patients is without exception satisfactory.


Predictors of seizure onset in Rett syndrome.
To investigate risk factors for seizure onset in Rett syndrome. Information on presence and age at onset of seizures, perinatal and developmental history, and genetic status was abstracted on 275 cases in the Australian Rett Syndrome Database. Cox and Weibull regression were used to investigate and provide a model for predicting the effects of genetic and developmental factors on age at seizure onset. Seizures were reported in 81% of 275 cases; the median age of onset was 48 months. Not having gained the ability to walk (P = .003) and developmental problems in the first 10 months of age (P = .04) were associated with an almost 2-fold increased risk of seizures. Cases without a detectable MECP2 mutation had a higher risk of seizure onset up to 4 years of age (P < .001) but a lower risk after 4 years (P = .08). Seizure onset in Rett syndrome is associated with early developmental factors and with genotype. Information on these factors can be used to predict age at seizure onset after diagnosis.


Immunotherapy using regulatory T cells in cancer suggests more flavors of hypersensitivity type IV.
Regulatory T cells (Tregs) profoundly affect tumor microenvironment and exert dominant suppression over antitumor immunity in response to self-antigen expressed by tumor. Immunotherapy targeting Tregs lead to a significant improvement in antitumor immunity. Intradermal injection of tumor antigen results in negative delayed-type hypersensitivity (DTH) type IV. However, anti-Tregs treatment/use of adjuvant along with tumor antigens turns DTH to positive. Considering Tregs as the earliest tumor sensor/responders, tumor can be regarded as Treg-mediated type IV hypersensitivity and negative DTH to tumor antigen is due to anti-inflammatory action of Tregs to tumor antigens at the injection site. Such a view would help us in basic and clinical situations to testify a candidate vaccine via dermal administration and evaluation of Treg proportion at injection site.


Role of statins in preventing cardiac surgery-associated acute kidney injury: an updated meta-analysis of randomized controlled trials.
The prevention of cardiac surgery-associated acute kidney injury (CSA-AKI) by statins remains controversial. Therefore, the present meta-analysis including randomized controlled trials (RCTs) was performed to assess the effect of perioperative statin on CSA-AKI. Two reviewers independently searched for RCTs about perioperative statin for prevention of CSA-AKI. The primary endpoint was CSA-AKI. Relative risk was calculated between statin and placebo for preventing CSA-AKI using the random-effect model or fixed-effect model according to different heterogeneity. Eight RCTs met inclusion criteria, including five studies with atorvastatin, two with rosuvastatin, and one with simvastatin. There were 1,603 patients receiving statin treatment and 1,601 with placebo. Perioperative statin therapy did not reduce the incidence of CSA-AKI (relative risk =1.17, 95% CI: 0.98-1.39, p=0.076). Furthermore, perioperative statin increased the risk of CSA-AKI in the subgroup analysis with clear definition of CSA-AKI and those with JADAD score >3. Perioperative rosuvastatin produced slightly significantly higher risk of AKI than atorvastatin therapy (p=0.070). Statin intervention both pre and post surgery slightly increased the risk of CSA-AKI versus preoperative statin therapy alone (p=0.040). Perioperative statin therapy might increase the risk of CSA-AKI after cardiac surgery.


Induction, partial purification and characterization of a hamster fibroblast protein kinase activity that phosphorylates ribosomal protein S6.
When BHK cells were grown to confluence and the growth medium replenished, there was a large and rapid increase in the phosphorylation of ribosomal protein S6. In postribosomal extracts of these cells, prepared in the presence of glycerol 2-phosphate and EGTA, a ribosomal protein S6 kinase was detected. The increase in activity of this protein kinase broadly reflected the increase in phosphorylation of ribosomal protein S6 observed in vivo. This ribosomal protein S6 kinase activity was substantially purified by a combination of phosphocellulose, DEAE-cellulose, Mono Q and heparin-Sepharose chromatography, and some of its characteristics were examined. When the products of phosphorylation of 40S ribosomal subunits by purified enzyme in vitro were analysed using two-dimensional gel electrophoresis, monophosphorylated and diphosphorylated forms of ribosomal protein S6 were observed to be the predominant radioactively labelled species.


Attitudes regarding life-sustaining measures in people born in Japan, China, and Vietnam and living in Texas.
Cultural beliefs about and preferences for care at the end of life are diverse and unique in many respects. This descriptive qualitative study presents findings about the attitudes and preferences of people born in Japan, China, and Vietnam and living in the southern part of the USA regarding life-sustaining measures. In-depth personal and focus group interviews were conducted with 46 participants and thematic analysis completed. The findings reflected some similarities and differences among the three groups concerning initiation and discontinuance of artificial nutrition and mechanical ventilation. They also demonstrated the requirement for sensitivity to individual needs when honouring the wishes of patients and surrogate decision makers. Interventional studies should follow that test educational strategies to improve practice outcomes for health-care providers who care for these populations at this vulnerable time of life.


The safety of triple antiplatelet therapy under thromboelastography guidance in patients undergoing stenting for ischemic cerebrovascular disease.
To investigate the safety of triple antiplatelet therapy (TAT) with cilostazol in patients undergoing stenting for extracranial and/or intracranial artery stenosis. A prospectively collected database was reviewed to identify patients who underwent stenting for extracranial and/or intracranial artery stenosis and showed resistance to aspirin and/or clopidogrel as assessed by pre-stenting thromboelastography (TEG) testing. Patients were assigned to a TAT group and a dual antiplatelet therapy (DAT) group. Major complications were defined as thromboembolic events (transient ischemic attack (TIA), ischemic stroke, and stent thrombosis) or major bleeding events within 30 days, and minor complications were defined as extracranial bleeding that did not require vascular surgery or transfusion within 30 days. A total of 183 patients were identified. The incidence of major complications was significantly lower in the TAT group than in the DAT group (TAT group vs. DAT group, 1/110 vs. 6/73; P=0.017). TIAs occurred in four patients, with one in the TAT group and three in the DAT group (1/110 vs. 3/73; P=0.303). Ischemic strokes occurred in three patients in the DAT group (TAT group vs. DAT group, P=0.062). No major bleeding events or stent thrombosis was recorded in either group. Two patients (one in each group) experienced minor complications that resolved without additional treatment (1/110 vs. 1/73; P>0.999). TAT under TEG guidance appears to be a safe antiplatelet strategy in patients undergoing stenting for extracranial and/or intracranial artery stenosis. By employing TAT under TEG guidance, favorable outcomes can be achieved in these patients.


A Versatile System for High-Throughput In Situ X-ray Screening and Data Collection of Soluble and Membrane-Protein Crystals.
In recent years, in situ data collection has been a major focus of progress in protein crystallography. Here, we introduce the Mylar in situ method using Mylar-based sandwich plates that are inexpensive, easy to make and handle, and show significantly less background scattering than other setups. A variety of cognate holders for patches of Mylar in situ sandwich films corresponding to one or more wells makes the method robust and versatile, allows for storage and shipping of entire wells, and enables automated crystal imaging, screening, and goniometer-based X-ray diffraction data-collection at room temperature and under cryogenic conditions for soluble and membrane-protein crystals grown in or transferred to these plates. We validated the Mylar in situ method using crystals of the water-soluble proteins hen egg-white lysozyme and sperm whale myoglobin as well as the 7-transmembrane protein bacteriorhodopsin from Haloquadratum walsbyi. In conjunction with current developments at synchrotrons, this approach promises high-resolution structural studies of membrane proteins to become faster and more routine.


Study of the Stereochemistry and Oxidation Mechanism of Plant Polyphenols, Assisted by Computational Chemistry.
In recent years, plant polyphenols have attracted great attention due to their wide range of biological activities. Certain kinds of polyphenols have complex structures; therefore, it is difficult to elucidate their total structure, including stereochemistry. In this study, we reinvestigated the stereostructures of two major C-glycosidic ellagitannins contained in Quercus plants, vescalagin and castalagin, and revised their stereostructures based on theoretical calculations of spectroscopic data. We also determined the structures of quercusnins A and B, isolated from the sapwood of Quercus crispula, based on theoretical calculations of NMR data. The oxidation mechanism of polyphenols has not been entirely elucidated. Therefore, we have also studied the oxidation mechanism of tea catechins during black tea production. Our investigation of the oxidation mechanism of black tea pigment theaflavins revealed that the difference in the position of the galloyl ester affords different oxidation products of theaflavins. In addition, oxidation products of pyrogallol-type catechins could be classified into three types-dehydrotheasinensins, theacitrins, and proepitheaflagallins; their detailed production and degradation mechanisms were also examined.


Periodontal treatment requirements of a group of defence forces' personnel.
The periodontal treatment requirements of 187 Royal Australian Air Force men aged 18-54 years based on clinical signs and symptoms were assessed. Every man required some treatment; 60 per cent needed surgery in one or more segments of the mouth.


David Skae and his nineteenth century etiologic psychiatric diagnostic system: looking forward by looking back.
The Kraepelinian syndromal approach to diagnosis taken by DSM-III and its successors, which defines disorders by their clinical phenomenon, has come under rising criticism with increasing calls for an etiologically based nosology. The relative virtues of a syndromal versus etiologic psychiatric nosology have actually been debated within our field for a long time. To deepen and historically contextualize our current discussion, I review in detail the proposal for etiologic diagnostic systems for insanity by David Skae (1814-1873). While his proposal was intuitive and appealing to some, others questioned its viability and utility pointing out a number of potential problems in its implementation that remain relevant today. Something critical might be lost for psychiatric disorders, they argued, if mental symptoms were removed from diagnostic criteria. Etiologically based diagnoses work best for mono-causal disorders and those where the causes all operate on the same scientific level. However, psychiatric disorders are highly multifactorial with a wide diversity of risk factors spread across biological, psychological and social-environmental domains so identification of a particular cause on which to base diagnoses would be difficult. Not only do individual risk factors contribute to many different disorders but most disorders are influenced by many etiologic factors. With respect to causes and disorders, psychiatry is characterized by a 'many to many' relationship which would make an etiologic nosologic system inherently problematic. Finally, causes and effects can be devilishly difficult to distinguish for psychiatric illness and, while clinically based nosologies aid in differential diagnosis, etiologically based system might not operate similarly.


Long non-coding RNA RAMS11 promotes metastatic colorectal cancer progression.
Colorectal cancer (CRC) is the most common gastrointestinal malignancy in the U.S.A. and approximately 50% of patients develop metastatic disease (mCRC). Despite our understanding of long non-coding RNAs (lncRNAs) in primary colon cancer, their role in mCRC and treatment resistance remains poorly characterized. Therefore, through transcriptome sequencing of normal, primary, and distant mCRC tissues we find 148 differentially expressed RNAs Associated with Metastasis (RAMS). We prioritize RAMS11 due to its association with poor disease-free survival and promotion of aggressive phenotypes in vitro and in vivo. A FDA-approved drug high-throughput viability assay shows that elevated RAMS11 expression increases resistance to topoisomerase inhibitors. Subsequent experiments demonstrate RAMS11-dependent recruitment of Chromobox protein 4 (CBX4) transcriptionally activates Topoisomerase II alpha (TOP2α). Overall, recent clinical trials using topoisomerase inhibitors coupled with our findings of RAMS11-dependent regulation of TOP2α supports the potential use of RAMS11 as a biomarker and therapeutic target for mCRC.


[Forensic assessment of DSM-5 posttraumatic stress disorder: a commentary on the transition from DSM-IV-TR (I)].
In May 2013 the American Psychiatric Association (APA) has released the latest and fifth edition of the diagnostic and statistical manual of mental disorders (DSM-5). Like its predecessor, the DSM-IV-TR, it will have considerable impact on the science of Psychiatry. The DSM-5 describes - actually available in English - the present medical knowledge about mental disorders. In the short run, German medical science and scientific medicolegal expertises will continue to rely on the German version of the DSM-IV-TR, however, they will be difficult to defend without bearing in mind the changes that DSM-5 brings about. This report discusses the transition from DSM-IV-TR to DSM-5 with regard to posttraumatic stress disorder (PTSD) and provides suggestions, how the criteria might be evaluated.


Objectively toward curriculum improvement in nursing education in England and Wales.
The General Nursing Council (G.N.C.) for England and Wales (circular 77/19/4) is currently influencing schools of nursing to use behavioural objectives, which means immediate implications for the basic training of nurses. As the majority of nurse teachers seek to influence their students' behaviour, there appears to be good grounds for stating clearly what it is they hope their students will achieve. Operationalizing objectives in realistic learning environments will rest on two fundamental assumptions. First, there must be a clear foundation of integrated theory and practice. Secondly, nurse teachers must be using objectives in the light of clear understanding of objective approaches which are based in a conceptual framework of curriculum theory.


Organic manure and urea effect on metolachlor transport through packed soil columns.
Application of organic manure (OM) amendments and nitrogen fertilizers can affect the sorption and movement of pesticides in soil. This study summarizes the sorption and leaching of metolachlor [2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylphenyl) acetamide] in soils after cow (Bos taurus) manure (2.5 and 5.0%) and urea (60 and 120 kg N ha(-1)) amendments in batch and column experiments. Both cow manure and urea applications increased metolachlor sorption in soils. The values of the Freundlich adsorption parameter K(r)(1/n) for treatments T0, T1 (OM), and T2 (OM) were 2.31, 3.32, and 3.96 in Soil 1; 2.02, 2.77, and 3.32 in Soil 2; and 1.10, 1.46, and 2.02 in Soil 3, respectively. Similarly, K(f)(1/n) values for treatment T1 (urea) and T2 (urea) were 2.37 and 2.84 in Soil 1; 2.16 and 2.83 in Soil 2; and 1.50 and 1.70 in Soil 3, respectively. Column leaching studies using Soil 1 indicated that OM application drastically reduced the metolachlor leaching losses from 50% (natural soil) to < 1.0% (5.0% OM amendment). Likewise, urea application also decreased metolachlor mobility and leaching losses in columns treated with 60 and 120 kg N ha(-1) urea were 33 and 20%, respectively. The reduction in the metolachlor leaching losses was achieved through the increase in the sorption capability of the OM- and urea-amended soil. Therefore, coapplication of metolachlor with cow manure or urea fertilizers will not enhance metolachlor mobility and reduces metolachlor leaching losses in low-organic-matter soil.


Challenges and opportunities in the treatment of adolescents with substance use disorder and suicidal behavior.
Many youth who present for substance abuse treatment report co-occurring suicidality. Therefore, it is important to learn about the characteristics of this population and effective treatment strategies. The purpose of this paper is to provide an overview of some of the key issues that arise when treating youth with substance abuse and co-occurring suicidality and to offer recommendations on how to approach these areas. Specifically, we discuss the potential utility of an integrated approach to treatment, and provide an overview of the characteristics of this treatment population, motivational and treatment engagement issues, the clinical management of suicidality in the context of treatment, and the effect of psychiatric comorbidity on treatment needs. We then discuss school, family, and peer issues that may arise as well as special considerations for the use of urine drug screens with this population. We conclude with recommendations for future treatment development research in this very important area.


Computational analysis of protein conformational heterogeneity.
In this paper, we applied the molecular dynamics (MD) simulations and used thermolysin as the system to study the overall protein dynamics and side chain dihedral angles across the Arrhenius break. Simulations were performed at a high temperature of 36 °C which is above the previously observed Arrhenius break, and the lower temperature of 20 °C which is below the Arrhenius break. We observed different protein dynamics and conformational heterogeneity of side chain dihedral angles of thermolysin at the two temperatures. Our results indicated that certain regions of thermolysin have a higher level of fluctuation at lower temperature. A temperature dependent dihedral angles were also observed at the two temperatures. The changes observed in the protein indicated key areas of temperature sensitivity within the protein.Communicated by Ramaswamy H. Sarma.


Excitation polarization provides structural resolution of individual non-blinking nano-objects.
We propose to combine the method of fluorescence intensity centroid localization with rotation of the plane of excitation polarization. Polarized light interacts selectively with differently oriented fluorophores; thus yielding topological information on the nanometer scale, without any need for fluorophore blinking. The method is applicable to photostable individual systems, when most of the traditional super-resolution methods fail. A theoretical study is supported by experiments on 30 nm long cyclodextrin-encapsulated single polyrotaxane conjugated polymer chains.


Seronegative Autoimmune Hepatitis: A Rare Manifestation of COVID-19.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus pandemic in 2019, commonly causes hepatic dysfunction. Liver injury ranges from mildly elevated liver enzymes to fulminant liver failure. Interestingly, there are cases that suggest a relationship between autoimmune hepatitis (AIH) in patients who either contracted coronavirus disease in 2019 (COVID-19) or were vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We present a case of a 39-year-old female without a significant past medical history who presented with two weeks of jaundice, abdominal pain, nausea, and diarrhea. She had significantly elevated liver enzymes and conjugated hyperbilirubinemia. She also tested positive for SARS-CoV-2 but denied any respiratory symptoms; her vaccination status was up to date. She denied taking hepatotoxic agents, and the workup was negative for acute viral hepatitis. The F-actin antibody level was 22 units, but serum immunoglobulin (IgG), anti-nuclear (ANA), anti-smooth muscle, anti-mitochondrial, anti-liver/kidney microsomal-1, anti-soluble liver antigen, and anti-neutrophil cytoplasmic antibodies levels were not elevated. Computerized tomography of the abdomen and pelvis revealed hepatic hemangiomas. Eventually, a liver biopsy was performed, and histology showed active lymphoplasmacytic hepatitis with prominent regenerative changes and areas of confluent necrosis. The histologic findings, along with the patient's clinical course, were suggestive of autoimmune hepatitis. The patient was started on systemic steroids with an improvement of abdominal pain and jaundice, as well as an improvement of her liver chemical profile. She was discharged with plans for hepatology clinic follow-up. Here, we present a rare case of seronegative AIH in a patient with a recent COVID-19 infection and discuss the potential underlying mechanism. We call for further investigation into the relationship between autoimmune dysfunction and COVID-19, as well as the pathophysiology behind it. Analyzing how the virus causes autoimmune dysfunction may allow clinicians to more effectively treat patients suffering from sequelae of COVID-19 infection, and it is important not to exclude autoimmune hepatitis from the differential based on the initial autoimmune workup.


Perceived clinical relevance and retention of basic sciences across the medical education continuum.
Medical programs are under pressure to maintain currency with scientific and technical advances, as well as prepare graduates for clinical work and a wide range of postgraduate careers. The value of the basic sciences in primary medical education was assessed by exploring the perceived clinical relevance and test performance trends among medical students, interns, residents, and experienced clinicians. A pilot study conducted in 2014 involved administration of a voluntary 60-item multiple-choice question test to 225 medical students and 4 interns. These participants and 26 teaching clinicians rated the items for clinical relevance. In 2016, a similarly constructed test (main study) was made a mandatory formative assessment, attempted by 563 students in years 2, 4, and 6 and by 120 commencing general practice residents. Test scores, performance trends, clinical relevance ratings, and correlations were assessed using relevant parametric and nonparametric tests. Rank order and pass-fail decisions were also reviewed. The mean test scores were 57% (SD 7.1) and 52% (SD 6.1) for the pilot and main studies, respectively. Highest scores were observed in pathology and social sciences. Overall performance increased with increasing year of study. Test scores were positively correlated with perceived relevance. There were moderate correlations (r = 0.50-0.63; P < 0.001) between participants' scores in the basic science and summative exams. Assessments may be key to fostering relevance and integration of the basic sciences. Benchmarking knowledge retention and result comparisons across topics are useful in program evaluation.


Proneness to hypomania/mania symptoms or depression symptoms and asymmetrical frontal cortical responses to an anger-evoking event.
The behavioral approach system (BAS) reflects the propensity to respond to signals of reward, including stimuli associated with safety and goal-oriented attack (e.g., anger). Hypomania/mania has been posited to involve increased BAS activity. In contrast, depression has been posited to involve decreased BAS activity. Building on past research, which suggests that increased left frontal cortical activity is a neurophysiological index of BAS activity, the present research tested the hypotheses that proneness toward hypomania/mania symptoms would be related to increased relative left frontal activity and that proneness toward depression symptoms would be related to decreased relative left frontal activity in response to an anger-evoking event. Results from 67 individuals who had completed a measure of proneness toward these affective symptoms and were exposed to an anger-evoking event supported the hypotheses.


Association of a full-day vs part-day preschool intervention with school readiness, attendance, and parent involvement.
Early childhood interventions have demonstrated positive effects on well-being. Whether full-day vs part-day attendance improves outcomes is unknown. To evaluate the association between a full- vs part-day early childhood program and school readiness, attendance, and parent involvement. End-of-preschool follow-up of a nonrandomized, matched-group cohort of predominantly low-income, ethnic minority children enrolled in the Child-Parent Centers (CPC) for the full day (7 hours; n = 409) or part day (3 hours on average; n = 573) in the 2012-2013 school year in 11 schools in Chicago, Illinois. The Midwest CPC Education Program provides comprehensive instruction, family-support, and health services from preschool to third grade. School readiness skills at the end of preschool, attendance and chronic absences, and parental involvement. The readiness domains in the Teaching Strategies GOLD Assessment System include a total of 49 items with a score range of 105-418. The specific domains are socioemotional with 9 items (score range, 20-81), language with 6 items (score range, 15-54), literacy with 12 items (score range, 9-104), math with 7 items (score, 8-60), physical health with 5 items (score range, 14-45), and cognitive development with 10 items (score range, 18-90). Full-day preschool participants had higher scores than part-day peers on socioemotional development (58.6 vs 54.5; difference, 4.1; 95% CI, 0.5-7.6; P = .03), language (39.9 vs 37.3; difference, 2.6; 95% CI, 0.6-4.6; P = .01), math (40.0 vs 36.4; difference, 3.6; 95% CI, 0.5-6.7; P = .02), physical health (35.5 vs 33.6; difference, 1.9; 95% CI, 0.5-3.2; P = .006), and the total score (298.1 vs 278.2; difference, 19.9; 95% CI, 1.2-38.4; P = .04). Literacy (64.5 vs 58.6; difference, 5.9; 95% CI, -0.07 to 12.4; P = .08) and cognitive development (59.7 vs 57.7; difference, 2.0; 95% CI, -2.4 to 6.3; P = .38) were not significant. Full-day preschool graduates also had higher rates of attendance (85.9% vs 80.4%; difference, 5.5; 95% CI, 2.6-8.4; P = .001) and lower rates of chronic absences (≥10% days missed; 53.0% vs 71.6%; difference, -18.6; 95% CI, -28.5 to -8.7; P = .001; ≥20% days missed; 21.2% vs 38.8%; difference -17.6%; 95% CI, -25.6 to -9.7; P < .001) but no differences in parental involvement. In an expansion of the CPCs in Chicago, a full-day preschool intervention was associated with increased school readiness skills in 4 of 6 domains, attendance, and reduced chronic absences compared with a part-day program. These findings should be replicated in other programs and contexts.


Ventilatory and heart rate responses after exercise in chronic cardiac failure.
1. To determine if the recovery period after exercise is abnormal in chronic cardiac failure, we studied 15 patients with stable chronic cardiac failure, and 14 normal subjects during and after symptom-limited maximal treadmill exercise. 2. In patients, O2 consumption fell exponentially from 16.8 (13.7-20.0) ml min-1 kg-1 at peak exercise to 6.0 (5.2-6.7) ml min-1 kg-1 at 3 min of recovery and in control subjects it fell from 30.2 (27.0-33.5) ml min-1 kg-1 to 6.7 (5.9-7.4) ml min-1 kg-1 (mean and 95% confidence intervals). The associated decay constants were slower in patients [0.70 (0.58-0.83) min-1 versus 0.93 (0.81-1.05) min-1 in control subjects (P < 0.01, t-test)]. 3. CO2 consumption kinetics displayed similar abnormalities [(k: 0.55 (0.41-0.69) min-1 versus 0.71 (0.59-0.83) min-1, P < 0.05)] and heart rate kinetics showed a similar trend [(k: 0.53 (0.33-0.74) min-1 versus 0.76 (0.62-0.89) min-1, P = 0.08]. 4. We conclude that patients with cardiac failure recover more slowly from exercise than normal subjects, and that this may further impair their ability to perform exercise, with consequent effect on quality of life.


The Application of Magnetic Bead Selection to Investigate Interactions between the Oral Microbiota and Salivary Immunoglobulins.
The effect of humoral immunity on the composition of the oral microbiota is less intensively investigated than hygiene and diet, in part due to a lack of simple and robust systems for investigating interactions between salivary immunoglobulins and oral bacteria. Here we report the application of an ex situ method to investigate the specificity of salivary immunoglobulins for salivary bacteria. Saliva collected from six volunteers was separated into immunoglobulin and microbial fractions, and the microbial fractions were then directly exposed to salivary immunoglobulins of "self" and "non-self" origin. Antibody-selected bacteria were separated from their congeners using a magnetic bead system, selective for IgA or IgG isotypes. The positively selected fractions were then characterized using gel-based eubacterial-specific DNA profiling. The eubacterial profiles of positively selected fractions diverged significantly from profiles of whole salivary consortia based on volunteer (P≤ 0.001%) and immunoglobulin origin (P≤ 0.001%), but not immunoglobulin isotype (P = 0.2). DNA profiles of separated microbial fractions were significantly (p≤ 0.05) less diverse than whole salivary consortia and included oral and environmental bacteria. Consortia selected using self immunoglobulins were generally less diverse than those selected with immunoglobulins of non-self origin. Magnetic bead separation facilitated the testing of interactions between salivary antibodies and oral bacteria, showing that these interactions are specific and may reflect differences in recognition by self and non-self immunoglobulins. Further development of this system could improve understanding of the relationship between the oral microbiota and the host immune system and of mechanisms underlying the compositional stability of the oral microbiota.


Site Occupancy Preference and Antithermal Quenching of the Bi2+ Deep Red Emission in β-Ca2P2O7:Bi2.
The resistance to thermal quenching is an essential factor in evaluating the performance of luminescent materials for application in white light emitting diodes (WLEDs). In this work, we studied the site occupancy preference and thermal quenching of luminescence in β-Ca2P2O7:Bi2+ red phosphor at low (10-300 K) and high temperatures (303-573 K). In β-Ca2P2O7, the host lattice has four different calcium sites, at which Bi2+dopant can be located. After comparing the change of bond energy when the Bi2+ ions are incorporated into the four calcium sites, we found out that Bi2+ would preferentially occupy the smaller energy variation sites Ci(2) and Ci(1) in this compound, which can be assigned to Bi(2) and Bi(1), respectively. Surprisingly, we noticed that the variation of emission intensity is different under different excitations when the temperature changes from 10 to 300 K. When exciting into the typical absorption of Bi(1) sites at 419 nm, the emission intensity at 300 K remains only 38% as compared to that at 10 K, while exciting into typical Bi(2) absorption at 460 nm, the emission intensity increases to 110%. When further increasing the temperature from 303 to 573 K, we observed a similar phenomenon, and the emission at 460 nm excitation starts to quench at 453 K. The emission intensity at 573 K still remains 86.1% of that at 303 K. This might be attributed to the Bi(2) → Bi(1) energy transfer. It is also evidenced by the time-resolved emission spectra and lifetime values. This work gives new insights into better understanding luminescent behaviors of Bi2+-doped materials with multiple cation sites. This should be helpful in the future when designing the bismuth doped phosphor for WLEDs with better resistance to thermal quenching.


Humanizing the self: moderators of the attribution of lesser humanness to others.
Three studies investigated moderators of the tendency to attribute greater humanness to the self than to others, an interpersonal counterpart of outgroup infra-humanization. Study 1 demonstrated that this self-humanizing effect is reduced when the other is the focus of comparison. Study 2 showed that the effect is reduced when the other is individuated. Study 3 indicated that empathy does not moderate self-humanizing: Self-humanizing failed to correlate negatively with dispositional empathy or perspective-taking. Study 3 also indicated that abstract construal moderates the self-humanizing effect using a temporal comparison. Participants rated their future self, but not their past self, as less human than their present self. Studies 1 and 3 also showed that self-humanizing is greater for undesirable traits: People may view their failings as "only human." All findings were distinct from those attributable to self-enhancement. Self-humanizing may reflect a combination of egocentrism, focalism, abstract representation of others, and motivated processes.


Insights on the mechanism of action of immunostimulants in relation to their pharmacological potency. The effects of imidazoquinolines on TLR8.
Imidazoquinolines are powerful immunostimulants (IMMS) that function through Toll-like receptors, particularly TLR7 and TLR8. In addition to enhancing the immune response, IMMS also function as antineoplastic drugs and vaccine adjuvants. These small compounds display almost the same molecular structure, except in some cases in which atom in position 1 varies and changes the imidazole characteristics. A variable acyclic side chain is also always attached at atom in position 2, while another chain may be attached at atom in position 1. These structural differences alter immune responses, such as the production of interferon regulatory factor and nuclear factor-κB (IRF-NFκB). In this work, quantum mechanics theory and computational chemistry methods were applied to study the physicochemical properties of the crystal binding site of TLR8 complexed with the following six IMMS molecules: Hybrid-2, XG1-236, DS802, CL075, CL097 and R848 (resiquimod). The PDB IDs of the crystals were: 4R6A, 4QC0, 4QBZ, 3W3K, 3W3J, and 3W3N respectively. Thus, were calculated, the total energy, solvation energy, interaction energy (instead of free energy) of the system and interaction energy of the polar region of the IMMS. Additionally, the dipole moment, electrostatic potential, polar surface, atomic charges, hydrogen bonds, and polar and hydrophobic interactions, among others, were assessed. Together, these properties revealed important differences among the six TLR8-immunostimulant complexes, reflected as different interaction energies and therefore different electrostatic environments and binding energies. Remarkably, the interaction energy of a defined polar region composed of the highly polarized N3, N5 atoms and the N11 amino group, acted as a polar pharmacophore that correlates directly with the reported immunopharmacological potency of the six complexed molecules. Based on these results, it was concluded that accurate physicochemical analysis of the crystal binding site could reveal the binding energy (measured as interaction energy) and associated molecular mechanism of action between IMMS and TLR8. These findings may facilitate the development and design of improved small molecules with IMMS properties that are targeted to the TLR system and have enhanced pharmacological effectiveness and reduced toxicity.


Association of Axillary Dissection With Systemic Therapy in Patients With Clinically Node-Positive Breast Cancer.
The role of axillary lymph node dissection (ALND) to determine nodal burden to inform systemic therapy recommendations in patients with clinically node (cN)-positive breast cancer (BC) is currently unknown. To address the association of ALND with systemic therapy in cN-positive BC in the upfront surgery setting and after neoadjuvant chemotherapy (NACT). This was a prospective, observational, cohort study conducted from August 2018 to June 2022. This was a preplanned study within the phase 3 randomized clinical OPBC-03/TAXIS trial. Included were patients with confirmed cN-positive BC from 44 private, public, and academic breast centers in 6 European countries. After NACT, residual nodal disease was mandatory, and a minimum follow-up of 2 months was required. All patients underwent tailored axillary surgery (TAS) followed by ALND or axillary radiotherapy (ART) according to TAXIS randomization. TAS removed suspicious palpable and sentinel nodes, whereas imaging-guidance was optional. Systemic therapy recommendations were at the discretion of the local investigators. A total of 500 patients (median [IQR] age, 57 [48-69] years; 487 female [97.4%]) were included in the study. In the upfront surgery setting, 296 of 335 patients (88.4%) had hormone receptor (HR)-positive and Erb-B2 receptor tyrosine kinase 2 (ERBB2; formerly HER2 or HER2/neu)-negative disease: 145 (49.0%) underwent ART, and 151 (51.0%) underwent ALND. The median (IQR) number of removed positive lymph nodes without ALND was 3 (1-4) nodes compared with 4 (2-9) nodes with ALND. There was no association of ALND with the proportion of patients undergoing adjuvant chemotherapy (81 of 145 [55.9%] vs 91 of 151 [60.3%]; adjusted odds ratio [aOR], 0.72; 95% CI, 0.19-2.67) and type of systemic therapy. Of 151 patients with NACT, 74 (51.0%) underwent ART, and 77 (49.0%) underwent ALND. The ratio of removed to positive nodes was a median (IQR) of 4 (3-7) nodes to 2 (1-3) nodes and 15 (12-19) nodes to 2 (1-5) nodes in the ART and ALND groups, respectively. There was no observed association of ALND with the proportion of patients undergoing postneoadjuvant systemic therapy (57 of 74 [77.0%] vs 55 of 77 [71.4%]; aOR, 0.86; 95% CI, 0.43-1.70), type of postneoadjuvant chemotherapy (eg, capecitabine: 10 of 74 [13.5%] vs 10 of 77 [13.0%]; trastuzumab emtansine-DM1: 9 of 74 [12.2%] vs 11 of 77 [14.3%]), or endocrine therapy (eg, aromatase inhibitors: 41 of 74 [55.4%] vs 36 of 77 [46.8%]; tamoxifen: 8 of 74 [10.8%] vs 6 of 77 [7.8%]). Results of this cohort study suggest that patients without ALND were significantly understaged. However, ALND did not inform systemic therapy recommendations.


Silencing platelet-derived growth factor receptor-β enhances the radiosensitivity of C6 glioma cells in vitro and in vivo.
Platelet-derived growth factor receptor (PDGFR)-β is an important tyrosine kinase and its downregulation has been reported to alter the radiosensitivity of glioma cells, although the underlying mechanism is unclear. In order to investigate the effect of PDGFR-β on the radiosensitivity of glioblastoma, the present study transfected C6 glioma cells with a PDGFR-β-specific small interfering (si)RNA expression plasmid, and downregulation of the expression of PDGFR-β in C6 glioma cells was confirmed by western blotting and immunohistochemical analysis. Clone formation assays and xenograft growth curves demonstrated that PDGFR-β-siRNA enhanced the radiosensitivity of C6 glioma cells in vitro and in vivo. Furthermore, MTT and xenograft growth curves demonstrated that PDGFR-β-siRNA inhibited the proliferation of C6 glioma cells in vitro and in vivo, and terminal deoxynucleotidyl transferase dUTP nick end-labeling and immunohistochemical analyses demonstrated that PDGFR-β-siRNA induced apoptosis and inhibited the expression of Ki-67, cyclin B1 and vascular endothelial growth factor in C6 glioma cell xenografts. Taken together, these results suggested that PDGFR-β may be used as a target for the radiosensitization of glioblastoma.


Alternative Splicing Dynamics During the Lifecycle of Salvia miltiorrhiza Root Revealed the Fine Tuning in Root Development and Ingredients Biosynthesis.
Alternative splicing (AS) is an essential post-transcriptional process that enhances the coding and regulatory potential of the genome, thereby strongly influencing multiple plant physiology processes, such as metabolic biosynthesis. To explore how AS affects the root development and synthesis of tanshinones and phenolic acid pathways in Salvia miltiorrhiza roots, we investigated the dynamic landscape of AS events in S. miltiorrhiza roots during an annual life history. Temporal profiling represented a distinct temporal variation of AS during the entire development stages, showing the most abundant AS events at the early seedling stage (ES stage) and troughs in 45 days after germination (DAG) and 120 DAG. Gene ontology (GO) analysis indicated that physiological and molecular events, such as lateral root formation, gravity response, RNA splicing regulation, and mitogen-activated protein kinase (MAPK) cascade, were greatly affected by AS at the ES stage. AS events were identified in the tanshinones and phenolic acids pathways as well, especially for the genes for the branch points of the pathways as SmRAS and SmKSL1. Fifteen Ser/Arg-rich (SR) proteins and eight phosphokinases (PKs) were identified with high transcription levels at the ES stage, showing their regulatory roles for the high frequency of AS in this stage. Simultaneously, a co-expression network that includes 521 highly expressed AS genes, SRs, and PKs, provides deeper insight into the mechanism for the variable programming of AS.


Designing educational messages to improve weaning food hygiene practices of families living in poverty.
This paper describes a methodology to design feasible interventions to improve weaning food hygiene practices of families living in extreme poverty. Educational messages to promote specific behavioural changes were defined and tested by utilizing a combination of ethnographic, survey and observational methods, and integrating viewpoints and suggestions of mothers and caretakers into the decision-making process. This new approach culminated in a household trial in which five groups, each of 15 non-practising mothers, were invited to adopt defined behaviours (handwashing before and after defined events, boiling water for reconstituting powdered milk, feeding gruel by spoon rather than bottlefeeding, not storing gruels and milks, and all four together). All initiated the advocated behaviours and most (53-80%) sustained the new behaviours and practised them every time during a one-month period. Of the four advocated behaviours, spoon-feeding was the most difficult to adopt wholly. The methodology was developed in response to the high priority given to reducing weaning food contamination for diarrhoeal disease control, and the lack of any existing methodology for defining appropriate educational interventions in resource-poor regions. This approach, with its combination of qualitative and quantitative methods and community focus, is recommended for future studies to design hygiene and other health education interventions in developing countries.


Thyroid hormone regulates endogenous amyloid-beta precursor protein gene expression and processing in both in vitro and in vivo models.
Thyroid hormone negatively regulates the amyloid-beta precursor protein (APP) gene in thyroid hormone receptor (TR)-transfected neuroblastoma cells. A negative thyroid hormone response element (nTRE) that mediates this regulation has been identified in the first exon of the APP gene. We demonstrate in an in vivo system that expression of APP mRNA, APP protein, and APP secretase cleavage products in mouse brain is influenced by thyroid status. Adult female mice were made hyperthyroid or hypothyroid for 3 weeks and compared to euthyroid mice. APP gene product expression was increased in hypothyroid mouse brain and reduced in hyperthyroid mouse brain, when compared to euthyroid controls. We observed similar effects of thyroid hormone on endogenous APP gene expression in human neuroblastoma cells. The incidence of hypothyroidism increases with age, and localized hypothyroidism of central nervous system has been reported in some patients with Alzheimer's disease (AD). Reduced action of thyroid hormone on the APP gene may contribute to AD pathology by increasing APP expression and the levels of processed APP products. These findings may be an underlying mechanism contributing to the association of hypothyroidism with AD in the elderly, as well as identifying a potential therapeutic target. Pharmacologic supplementation of thyroid hormone, or its analogs, may reduce APP gene expression and beta amyloid peptide accumulation.


RB and apoptotic cell death.
Homeostasis of cell numbers is achieved by balancing the proliferative and death states of cells. Proper regulation in a cell requires an accurate coordination between these two processes. Indeed, dysregulation of cell cycle progression is essential for the initiation of apoptosis. Retinoblastoma protein (RB) is an important tumor suppressor and a cell cycle regulator. Most recent studies suggest that RB also plays a regulatory role in the process of apoptosis. During the onset of apoptosis, the hyperphosphorylated form of RB (p120/hyper) is converted to a hypophosphorylated form (p115/hypo), which is mediated by a specific protein-serine/ threonine phosphatase activity. Accompanied by the internucleosomal fragmentation of DNA, the newly formed p115/hypo/RB is immediately cleaved by a protease that has properties of the caspase family. During apoptosis, RB is also cleaved in its carboxyl terminus by a caspase-3-like activity. By contrast, the unphosphorylated form of RB (p110/unphos) remains uncleaved during apoptosis. Further studies suggest that p110/unphos/RB functions as an inhibitor of apoptosis. Therefore, regulation of the RB proteolytic activities and consequent RB levels is important for the determination of cellular fate.


Fasting plasma glucose correlates with angiographic coronary artery disease prevalence and severity in Chinese patients without known diabetes.
Type 2 diabetes mellitus is a risk factor for coronary artery disease (CAD). While there is a clear association of fasting plasma glucose (FPG) with microvascular complications, the risk for CAD conferred by FPG is relatively less clear. Therefore, we investigate the association between different FPG and the prevalence and severity of angiographic CAD in high-risk Chinese patients without known diabetes. Among 1,419 subjects who were to undergo coronary angiography for the confirmation of suspected myocardial ischemia, 906 subjects without known diabetes were included in this study and categorized into four groups according to the level of FPG: group 1, ≤5.5 mmol/l; group 2, 5.6-6.0 mmol/l; group 3, 6.1-6.9 mmol/l; and group 4, ≥7.0 mmol/l. Significant angiographic CAD was defined as ≥50 % lumen diameter reduction in at least one major coronary artery in a given subject. The severity and extent of coronary atherosclerosis were defined as the number of diseased vessels, the proportion of totally occluded vessel and the Gensini score. Associations between FPG and the prevalence and severity of CAD were assessed by logistic and linear stepwise regression analyses. The angiographic CAD prevalence, the number of diseased vessels, the totally occluded vessel, and the Gensini score increased corresponding to increasing FPG levels from ≤5.5 mmol/l to 5.6-6.0 mmol/l to 6.1-6.9 mmol/l to ≥7.0 mmol/l (P < 0.05). The FPG had significant association with angiographic CAD (adjusted OR, 1.53; 95 % CI, 1.19-1.98; P = 0.001) and the Gensini score (standardized regression coefficient = 0.172, P = 0.011). Compared with group 1, group 2, 3 and 4 demonstrated significantly higher CAD prevalence after adjustment (adjusted OR, 1.61 [1.16-2.19]; P = 0.015 for group 2; 1.49 [1.11-2.59]; P = 0.027 for group 3; and 4.19 [2.85-6.16]; P = 0.024 for group 4, respectively). FPG group was also significantly associated with the Gensini score (Standardized coefficients, 0.185; P = 0.007, respectively). FPG was an independent risk factor for the prevalence and severity of significant angiographic CAD in our study population. The severity of angiographic CAD increased along with the increasing FPG levels even in prediabetic state.


Chiral Heterobimetallic Bismuth-Rhodium Paddlewheel Catalysts: A Conceptually New Approach to Asymmetric Cyclopropanation.
Cyclopropanation reactions of styrene derivatives with donor-acceptor carbenes formed in situ are significantly more enantioselective when catalyzed by the heterobimetallic bismuth-rhodium complex 5 a endowed with N-phthalimido tert-leucine paddlewheel ligands rather than by its homobimetallic dirhodium analogue 1 a. This virtue is likely the result of two synergizing factors: the conical shape of 5 a translates into a narrower calyx-like chiral binding site about the catalytically active Rh center; the Bi atom, although fully solvent exposed, does not decompose aryl diazoacetates and is hence incapable of promoting a racemic background reaction. Moreover, ligand variation proved that successful catalyst design mandates that the anisotropy of the conical heterobimetallic core be matched by proper directionality of the ligand sphere.


Suppression of immune responses by dendritic cells infected with HIV.
Evidence of human immunodeficiency virus (HIV) replication both in the skin Langerhans' cells of AIDS patients (Tschachler et al., 1987) and in normal, peripheral blood dendritic cells (DC) (Patterson & Knight, 1987; Knight & Patterson, 1989) suggests that infection of these antigen-presenting cells may contribute to the immunosuppression seen in AIDS. Support for this hypothesis is now provided by experiments in which the capacity of DC infected in vitro to present mitogen to normal syngeneic lymphocytes was measured. Infecting DC with HIV before culturing with lymphocytes inhibited mitogen-stimulated cell proliferation. Viral DNA was detected in DC in these cultures by in situ hybridization but, in addition, HIV was also present in a small proportion of lymphocytes. However, introducing an inhibitor of virus replication, 2',3' dideoxyadenosine, after infection of the DC but before culturing with lymphocytes, blocked growth of HIV in lymphocytes. In these latter experiments mitogen proliferation responses were still suppressed. Infection of DC could, therefore, cause immunosuppression in AIDS, both by direct effect on antigen-presentation and by the transfer of HIV to T cells.


Clinical variations in assessment of bull's-eye maculopathy.
To evaluate the phenotypic variation in bull's-eye maculopathy and seek possible correlations between functional loss and clinical appearance. From January 1, 1999, to September 30, 2000, we prospectively examined patients with bull's-eye lesions. Age of onset, duration of symptoms, visual acuity, clinical appearance, and autofluorescence images were recorded, the area of atrophy measured, and electrophysiologic investigations performed. Forty-seven patients, including 6 sibling pairs, met the study entry criteria. On the basis of autofluorescence imaging, 3 distinct groups were identified. Group 1 showed a distinct ring of increased autofluorescence surrounding an area of decreased autofluorescence. In group 2, the ring of increased autofluorescence was not present. Group 3 displayed a speckled appearance within the affected area. All patients had evidence of central sparing in an area of centrally increased autofluorescence. There was significant correlation with the age of onset, visual acuity, and duration of disease. Electrophysiologic tests revealed that 28 patients had macular dysfunction only, 14 had cone-rod dystrophy, 3 had rod-cone dystrophy, and only 2 (monozygotic twins) had cone dystrophy. The correlation between electrophysiologic and autofluorescence data was poor. The sibling pairs had concordant autofluorescence appearance, but electrophysiologic grouping differed in 2 pairs. Bull's-eye maculopathy represents a heterogeneous group of disorders. The clinical appearance was not helpful in assessing the degree of retinal dysfunction. The difference in qualitative characteristics of functional loss between siblings implies that these attributes do not necessarily reflect the influence of the primary mutation.


Comparison of Quantitative Antifungal Testing Methods for Textile Fabrics.
Quantitative antifungal testing methods for textile fabrics under growth-supportive conditions were studied. Fungal growth activities on unfinished textile fabrics and textile fabrics modified with Ag nanoparticles were investigated using the colony counting method and the luminescence method. Morphological changes of the fungi during incubation were investigated by microscopic observation. Comparison of the results indicated that the fungal growth activity values obtained with the colony counting method depended on the morphological state of the fungi on textile fabrics, whereas those obtained with the luminescence method did not. Our findings indicated that unique characteristics of each testing method must be taken into account for the proper evaluation of antifungal activity.


Specialization in membrane structure and metabolism with respect to polyunsaturated lipids.
The principal features of the hypotheses presented here are presented in a model (Figure 8). Polyunsaturated phospholipids are preferentially localized on the cytosolic leaflet of the plasma membrane and around proteins. They influence the physical state of these microenvironments and thereby help to regulate cellular functions. Losses of these species due to phospholipase attack, dietary deprivation or other pathological stimuli (such as alcohol), may lead to drastic alterations in some of these functions. The PUFA's released, including 22:6 omega 3, can be metabolised by a lipoxygenase enzyme in the brain and platelet and the products formed are biologically active.


[The Role of Blood Urea Nitrogen and C-Reactive Protein and Their Ratios to Albumin in Predicting Mortality in Crimean-Congo Hemorrhagic Fever].
Crimean-Congo hemorrhagic fever (CCHF) is an acute febrile hemorrhagic disease that can be fatal. Almost one-eighth of people infected with CCHF develop serious illness. The mortality rate is high due to severe bleeding, diffuse intravascular coagulation, shock, and multiple organ failure. Early detection of serious illness can play a key role in developing effective treatment and follow-up strategies. C-reactive protein (CRP), blood urea nitrogen (BUN), and albumin have previously been evaluated as markers of clinical severity in infectious diseases. This study aimed to evaluate the role of these readily available and inexpensive biomarkers and their ratios as predictors of mortality risk in patients with CCHF. This retrospective observational single-center study was conducted between May and October 2022 in a regional hospital in northeastern Türkiye, where the incidence of CCHF is the highest. Hundred and fifty patients aged 18 years and over with a definitive diagnosis of CCHF were included; patients with chronic kidney disease requiring long-term hemodialysis and those with missing data were excluded from the study. The patients' demographic characteristics, comorbidities, initial complaints, and epidemiological, clinical, and laboratory findings were recorded. Receiver operating characteristics (ROC) curve analysis was used to determine the predictive power of the studied biomarkers. Categorical and continuous variables found to be significant for mortality were evaluated using univariate logistic regression. Variables found to be significant in this test were used to create a multivariate logistic regression model to identify independent risk factors for mortality. The median age of the patients was 49 (18-89) years and 93 (62.0%) were men. Twelve patients (8.0%) required intensive care and 11 (7.3%) died. Complaints of abdominal pain (p= 0.010), hypotension (p= 0.002), somnolence (p< 0.001), and bleeding (p< 0.001) at the time of hospital admission were significantly more common among non-surviving patients. BUN and CRP were the biomarkers with the highest diagnostic power for mortality. A BUN cut-off value of 19.5 mg/dl had 100% sensitivity and 74.1% specificity, while a CRP cut-off value of 31.5 mg/L had 100% sensitivity and 81.8% specificity. CRP/albumin ratio (CAR) and BUN/albumin ratio (BAR) had higher predictive power than all individual biomarkers. At a cut-off point of 0.98, CAR had diagnostic power of 0.942 (95% confidence interval= 0.901-0.984), 100% sensitivity, and 84.9% specificity for mortality. At a cut-off of 0.50, BAR predicted mortality with diagnostic power of 0.932 (95% confidence interval= 0.879-0.984), 100% sensitivity, and 81.3% specificity. In univariate logistic regression analysis, the presence of bleeding, somnolence, and hypotension at the time of admission; higher troponin, total bilirubin, neutrophil count, activated partial thromboplastin time, prothrombin time, and age; and lower platelet count, fibrinogen, low-density lipoprotein cholesterol, and total cholesterol were significant risk factors determined for poor prognosis. Multivariate logistic analysis performed with these parameters revealed that somnolence, CAR, and BAR were independent risk factors for predicting mortality in CCHF. In conclusion, BAR and CAR, more easily and quickly obtained than severity scores, had higher sensitivity and specificity in predicting mortality than single biomarkers, and can be used during hospital admission for CCHF.


Aqua-(2,2'-diamino-4,4'-bi-1,3-thia-zole-κN,N)(thio-diacetato-κO,S,O')nickel(II) monohydrate.
In the title compound, [Ni(C(4)H(4)O(4)S)(C(6)H(6)N(4)S(2))(H(2)O)]·H(2)O, the Ni(II) cation assumes a distorted octa-hedral coordination geometry formed by a diamino-bithia-zole (DABT) ligand, a thio-diacetate (TDA) dianion and a coordinated water mol-ecule. The tridentate TDA chelates to the Ni cation in a facial configuration, and both chelating rings display the envelope conformations. The two thia-zole rings of the DABT ligand are twisted with respect to each other, making a dihedral angle of 9.96 (9)°. Extensive O-H⋯O, N-H⋯O and weak C-H⋯O hydrogen bonding is present in the crystal structure.


A pilot study: the relationship between salivary MCP-1 and IgA, and exercise performance in long-distance runners and sprinters.
It remains unclear that the relationship between sprint and/or endurance performance and salivary immunological factors and stress hormones in athletes. The aim of this study was to investigate if salivary immunological factors and stress hormones are related to sprint and endurance performance in sprinters and long-distance runners. Fourteen male sprinters provided 100-m record and 22 male long-distance runners provided 5000-m record. Salivary IgA, MCP-1, interleukin-8, and cortisol levels in sprinters and long-distance runners were measured by ELISA assay. No significant differences were found in all salivary parameters between sprinters and long-distance runners. In long-distance runners, the salivary IgA and MCP-1 concentrations and secretory rate significantly correlated with their personal best 5000-m times (r = 0.534, P = 0.011; r = 0.567, P = 0.006; r = 0.452, P = 0.035, respectively). In sprinters, the salivary IgA concentration, MCP-1 concentration, and MCP-1 secretory rate did not correlate with personal best 100-m sprint times (r = - 0.260, P = 0.369; r = 0.128, P = 0.663; r = 0.122, P = 0.677, respectively). Therefore, the present study is the first to determine that immunological factors such as IgA and MCP1 may be related to endurance performance in long-distance runners.


[Genetic diversity of flat-headed vole (Alticola strelzowi (Kastschenko, 1899)) inferred from cytochrome b variation].
Variation of the cytochrome b gene fragment was examined in 27 flat-headed voles Alticola strelzowi from different parts of the species range. A total of 15 haplotypes were described, while the species as a whole was characterized by low levels of genetic differentiation and polymorphism. The haplotypes fell into three haplogroups, one of which corresponded to the subspecies A. s. strelzowi, and the other two, to A. s. desertorum. Based on different index values, the level of genetic polymorphism in the later subspecies was considered to be higher than in the first one. Phylogeographic analysis suggested post-glacial dispersal of flat-headed voles from a single refugium located in Western Altai. Using different techniques, relatively recent colonization of the Central Altai territory was demonstrated (subspecies A. s. strelzowi), which determined low level of genetic variation in this territory.


Age-Related Quality of Life and Psychosocial Impact of Chin Asymmetry in Adolescents and Young Adults Undergoing Orthodontic and Orthognathic Correction.
Craniofacial asymmetry can have significant psychosocial implications, affecting the quality of life in adolescents and young adults. This study aimed to assess the impact of age and complexity of craniofacial asymmetry on quality of life and psychosocial outcomes in patients undergoing orthodontic and orthognathic correction. A cross-sectional study was conducted on 149 patients aged 13-26 years with moderate or severe craniofacial asymmetry that had a gnathion deviation higher than 2 mm, according to the American Association of Orthodontists. Participants were divided into three groups: teenagers (n = 53), adults (n = 46), and a control group (n = 50) with relative craniofacial asymmetry. Quality of life and psychosocial impacts were evaluated using validated questionnaires that measure health-related quality of life (SF-36), body image satisfaction and self-acceptance (BIQLI), anxiety and depression levels (HADS), and perceived stress (PSS-10). These tools provided an encompassing appraisal of the psychological and social implications associated with craniofacial asymmetry before and six months after orthodontic and orthognathic correction. Before the intervention, adults had higher mental health scores compared to teenagers (p = 0.037). At the 6-month follow-up, no significant differences in mental health scores were observed between the two groups (p = 0.121). BIQLI results showed significant differences in satisfaction with appearance and self-acceptance between teenagers and adults, both before intervention (p = 0.045 and p = 0.051, respectively) and at six months (p = 0.062 and p = 0.031, respectively). HADS results showed significant differences in anxiety levels before intervention (p = 0.039) but not at six months (p = 0.133). PSS-10 results showed no significant differences in perceived stress between the groups. In conclusion, this study demonstrates that craniofacial asymmetry significantly impacts the quality of life and psychosocial well-being of adolescents and young adults. Specifically, teenagers, as compared to young adults, reported lower satisfaction with their appearance and lower self-acceptance before intervention, underscoring the profound psychosocial challenges that adolescents with craniofacial asymmetry may experience. These age-related differences underscore the importance of tailored interventions to address unique psychosocial needs at different developmental stages.


[Development of immersion therapy in Mongolian medicine].
Being a tropical therapeutic measure, immersion therapy of Mongolian medicine includes mineral therapy, sebsu therapy, medical bath, liquid spraying and others. They have a long history and were recorded in Chinese or Mongolian medical works. Its provenance is closely related to the nomadic culture of the Mongolian plateau.


The effects of preceding exercise on myocardial damage in rats.
[Purpose] The purpose of this study was to investigate the effects of exercise on myocardial injury in male Sprague-Dawley rats. Two groups of rats were trained with either moderate- or high-intensity treadmill running for four weeks. Subsequently, the concentrations of cardiac troponin and the N-terminal of prohormone brain natriuretic peptide (NT-proBNP) were examined following a single bout of prolonged intensive exercise (lasting 3 h). [Subjects and Methods] The study included 40 six-week-old male Sprague-Dawley rats weighing 150-180 g each. The aerobic exercise group was divided into high-intensity (28 m/min) and moderate-intensity (15 m/min) subgroups. Both subgroups were trained for 35 min daily for six days per week (excluding Sunday) over a four-week period. Following training, the high- and moderate-intensity exercise groups and a nonexercise group performed one bout of prolonged treadmill exercise for 3 h at a speed of 15 m/min. [Results] The cardiac troponin and NT-proBNP levels differed significantly between the groups. [Conclusion] The exercise groups showed lower levels of cardiac troponin and NT-proBNP than the nonexercise group after the bout of prolonged intensive exercise.


Incidence and Prognosis of Pericarditis After ST-Elevation Myocardial Infarction (from the Acute Coronary Syndrome Israeli Survey 2000 to 2013 Registry Database).
There are scarce contemporary data regarding the incidence and prognosis of early postmyocardial infarction pericarditis (PMIP). Thus, we retrospectively analyzed 6,282 patients with ST-segment elevation myocardial infarction (STEMI) enrolled with known PMIP status in the Acute Coronary Syndrome Israeli Survey 2000 to 2013 registry. The primary outcome was the composite of all-cause mortality, nonfatal myocardial infarction, cerebrovascular event, stent thrombosis, or revascularization. The secondary outcomes were mortality and length of stay during the acute hospitalization. Overall, 76 patients with STEMI had PMIP (1.2%). PMIP incidence gradually decreased from 170 per 10,000 in 2000 to 110 per 10,000 in 2013, respectively (35% reduction, p for trend = 0.035). Patients with PMIP were younger (median 58.0 vs 61.0; p = 0.045), had less hypertension, higher cardiac biomarkers, and more frequently reduced left ventricular ejection fraction (87.0% vs 67.0%; p = 0.001). Patients with PMIP had longer time to reperfusion (225 minutes vs 183 minutes; p = 0.016) and length of stay (7.0 vs 5.0 days; p < 0.001). The composite end point occurred similarly in patients with and without PMIP (10.5% vs 13.2%, respectively). There was no significant difference in 30-day, 1-year, and 5-year survival. In conclusion, PMIP is a relatively rare complication of STEMI in the coronary reperfusion era, portends worse short-term but not long-term outcomes, and is associated with bigger infarct size.


Direct aqueous determination of glyphosate and related compounds by liquid chromatography/tandem mass spectrometry using reversed-phase and weak anion-exchange mixed-mode column.
Analysis of the broad-spectrum herbicide glyphosate and its related compounds is quite challenging. Tedious and time-consuming derivatization is often required for these substances due to their high polarity, high water solubility, low volatility and molecular structure which lacks either a chromophore or fluorophore. A novel liquid chromatography/tandem mass spectrometry (LC/MS-MS) method has been developed for the determination of glyphosate, aminomethylphosphonic acid (AMPA) and glufosinate using a reversed-phase and weak anion-exchange mixed-mode Acclaim® WAX-1 column. Aqueous environmental samples are directly injected and analyzed in 12 min with no sample concentration or derivatization steps. Two multiple reaction monitoring (MRM) channels are monitored in the method for each target compound to achieve true positive identification, and ¹³C, ¹⁵N-glyphosate is used as an internal standard to carry out isotope dilution mass spectrometric (IDMS) measurement for glyphosate. The instrument detection limits (IDLs) for glyphosate, AMPA and glufosinate are 1, 2 and 0.9 μg/L, respectively. Linearity of the detector response with a minimum coefficient of determination (R² value (R² > 0.995) was demonstrated in the range of ∼10 to 10³ μg/L for each analytes. Spiked drinking water, surface water and groundwater samples were analyzed using this method and the average recoveries of analytes in three matrices ranged from 77.0 to 102%, 62.1 to 101%, 66.1 to 93.7% while relative standard deviation ranged from 6.3 to 10.2%, 2.7 to 14.8%, 2.9 to 10.7%, respectively. Factors that may affect method performance, such as metal ions, sample preservation, and storage time, are also discussed.


Photodamage in deep tissue two-photon optical biopsy of human skin.
Photodamage, induced by femtosecond laser radiation, was studied in thick samples of human skin tissue (healthy skin and neoplastic lesions). Photobleaching, photoionization, and thermomechanical damage effects were characterized comparatively. The laser power dependence of the damage rates allowed to connect macroscopic effects to underlying molecular processes. Optical effects were correlated to histopathological changes. Tissue alterations were found only from thermomechanical cavitation and limited to superficial layers of the epidermis. From the depth-dependencies of all damage thresholds a depth-dependent power-compensation scheme was defined allowing for damage-free deep tissue optical biopsy. Damage-induced luminescence pattern for different excitation powers and a corresponding threshold analysis.


Effect of natural geotextile on the cotransport of heavy metals (Cu2+, Pb2+, and Zn2+) and kaolinite particles.
A cotransport study of heavy metals and kaolinite particles in sand column with and without flax geotextiles was carried out. The objectives were to evaluate the potential role of kaolinite in heavy metals transfer and to analyse the influence of flax geotextiles on the transfer of these pollutants. The adsorption rates of heavy metals on the kaolinite particles were, respectively, 53%, 65% and 25% for copper, lead, and zinc. The injection of kaolinite with heavy metals resulted in a significant decrease in the retention efficiency of copper and lead in the filter. The presence of kaolinite in the injected solution has virtually no influence on the effectiveness of zinc fixation in the filter. The retention of heavy metals is in the order of Zn > Cu > Pb with a significant drop of retention efficiency of 34% for copper, 67% for lead, and less than 1% for zinc. The presence of kaolinite in the injected solution reversed the retention order of heavy metals when metals solution was injected alone. Flax geotextiles increase the ability of the filter to retain soluble and attached heavy metals. It improves the sand retention capacity and it retains soluble and attached metals in its structure.


Psychosocial Problems among Psychiatric Nurses for Caring Patients with Mental Disorders during the COVID-19 Pandemic.
COVID-19 has a negative effect on the psychological well-being of psychiatric nurses. Thus, examining the psychosocial response of nurses is important for preventing more serious mental health problems and disruption of the quality of nursing care. This study aimed to evaluate the psychosocial problems of nurses who provided nursing care to patients with mental health disorders during the COVID-19 pandemic. A quantitative study with a cross-sectional design was conducted. The 101 nurses at Central Mental Health Hospital who provide nursing care to patients with mental health disorders were recruited through consecutive sampling. The instruments used were the demographic questionnaire, the Expanded Nursing Stress Scale, Zung Self-Rating Anxiety Scale, and The Connor-Davidson Resilience Scale 25. Univariate and bivariate analyses were used to process the data. The mean score of 45.1 (±24.3) was obtained for the ENSS; around 97% of nurses have a work stress score below the average, 4.95% have mild-moderate anxiety, and 28.7% have a low level of resilience. Work stress and contact frequency, work stress and gender, anxiety and contact frequency, as well as resilience and contact frequency all correlated significantly (p value <0.05). The Pearson test showed a significant positive correlation between work stress and anxiety (p: 0.002, r: 0.299). However, there was no significant correlation between anxiety and resilience (p: 0.643, r: 0.47), nor between work stress and resilience (p: 0.643; r: 0.47). Psychosocial disorders that psychiatric nurses face include occupational stress, mild-moderate anxiety, and low resilience. The government can create specific infection control guidelines for the mental health setting, and hospital management or ward leaders can also provide support to psychiatric nurses to increase resilience in reducing psychosocial problems.


Velocity of a Molecule Evaporated from a Water Nanodroplet: Maxwell-Boltzmann Statistics versus Non-Ergodic Events.
The velocity of a molecule evaporated from a mass-selected protonated water nanodroplet is measured by velocity map imaging in combination with a recently developed mass spectrometry technique. The measured velocity distributions allow probing statistical energy redistribution in ultimately small water nanodroplets after ultrafast electronic excitation. As the droplet size increases, the velocity distribution rapidly approaches the behavior expected for macroscopic droplets. However, a distinct high-velocity contribution provides evidence of molecular evaporation before complete energy redistribution, corresponding to non-ergodic events.


How phenotype guides management of non-conventional squamous cell carcinomas of the larynx?
Although the majority of laryngeal malignancies are the conventional squamous cell carcinomas (SCC), a wide variety of malignant epithelial tumors can affect the larynx. Current treatment guidelines are designed to guide clinicians in management of conventional laryngeal SCC. Less is known about the biological behavior and responsiveness to therapy and overall outcomes of other malignant epithelial lesions. Because a spectrum of disease biology is represented by these rare phenotypes, an understanding of the basic biology can help direct management to optimize clinical outcome in this group of patients. This review provides a critical analysis of literature relating to the diagnosis, management, and outcome of patients with non-conventional squamous malignant epithelial neoplasms of the larynx. Particular attention is paid to features which are at variance with the conventional SCC and how these impact on management of these rare tumors.


Real-Time PCR to Phenotype Resistance to the Citrus Nematode Tylenchulus semipenetrans Cobb.
As pest management options, such as nematicides, become more restrictive, developing rootstocks resistant to the citrus nematode is fundamental for citrus production. This study provides an updated methodology to screen for citrus nematode resistance in rootstock-breeding programs. We developed a novel method to extract female citrus nematodes from roots that is suitable for molecular work and a real-time-PCR-based nematode quantification method for Tylenchulus semipenetrans. These procedures allow scaling up screening to high-throughput workflows, increasing the chances of finding rootstock candidates that combine all the desired traits. Our results contribute to the growing literature supporting quantification of nematodes with molecular methods.


X-ray tomography for structural analysis of microstructured and multimaterial optical fibers and preforms.
Specialty optical fibers, in particular microstructured and multi-material optical fibers, have complex geometry in terms of structure and/or material composition. Their fabrication, although rapidly developing, is still at a very early stage of development compared with conventional optical fibers. Structural characterization of these fibers during every step of their multi-stage fabrication process is paramount to optimize the fiber-drawing process. The complexity of these fibers restricts the use of conventional refractometry and microscopy techniques to determine their structural and material composition. Here we present, to the best of our knowledge, the first nondestructive structural and material investigation of specialty optical fibers using X-ray computed tomography (CT) methods, not achievable using other techniques. Recent advances in X-ray CT techniques allow the examination of optical fibers and their preforms with sub-micron resolution while preserving the specimen for onward processing and use. In this work, we study some of the most challenging specialty optical fibers and their preforms. We analyze a hollow core photonic band gap fiber and its preforms, and bond quality at the joint between two fusion-spliced hollow core fibers. Additionally, we studied a multi-element optical fiber and a metal incorporated dual suspended-core optical fiber. The application of X-ray CT can be extended to almost all optical fiber types, preforms and devices.


Persistent vertical diplopia after cataract surgery: a case report.
Diplopia is an event that can occur following cataract surgery, although its rate of occurrence is limited and ranges from 0.67% to 0.85%. The authors present a case of vertical diplopia arising after peribulbar anaesthesia for cataract surgery in a 78-year-old woman. Diplopia appeared at distance in primary position, while at near there was binocular single vision. Stereopsis was present at the Lang I - II Test, but the Wirth Test was incomplete. Although in the literature the frequency of these "accidents" is very limited, we think it is relevant to emphasize the need to perform pre-operative routine using a careful orthoptic examination along with a thorough medical, especially strabological, history.


SIGNIFICANT ROLE FOR HISTORICAL EFFECTS IN THE EVOLUTION OF REPRODUCTIVE ISOLATION: EVIDENCE FROM PATTERNS OF INTROGRESSION BETWEEN THE CYPRINID FISHES, LUXILUS CORNUTUS AND LUXILUS CHRYSOCEPHALUS.
Samples of Luxilus cornutus, Luxilus chrysocephalus, and their hybrids were collected along hypothesized routes of dispersal from Pleistocene refugia to examine the significance of geographic variation in patterns of introgression between these species. Patterns of allozyme and mitochondrial DNA (mtDNA) variation were generally consistent with those from previous studies. Tests of Hardy-Weinberg equilibrium revealed significant deficiencies of heterozygotes in all samples, indicating some form of reproductive isolation. Mitochondrial DNAs of each species were not equally represented in F1 hybrids; however, this bias was eliminated when the two largest samples were excluded from the analysis. Backcross hybrids exhibited biased mtDNA introgression, as samples from Lake Erie (eastern) and Lake Michigan (western) drainages showed significant excesses of mtDNAs from L. chrysocephalus and L. cornutus, respectively, relative to frequencies of diagnostic allozyme markers. The extent and direction of allozyme and mtDNA introgression was quantified by calculating isolation index values from morphologically "pure" individuals of each species from each locality. Analysis of variance of these measures identified limited introgression of allozyme variants with no geographic pattern, but significant differences in direction of mtDNA introgression between drainages (i.e., postglacial dispersal route). Association between patterns of mtDNA introgression and dispersal route across the latitudinal width of the contact zone is best explained by genetic divergence during past isolation of ancestral populations from these drainages. These results identify a significant role for historical effects in the evolution of reproductive isolation and the process of speciation.


Differential effects of prandial and non-prandial GLP-1 receptor agonists in type 2 diabetes therapy.
In type 2 diabetes mellitus (T2DM), decreased pancreatic beta-cell function and increased insulin resistance contribute to a steady decline in glucose homeostasis. Maintaining levels of glycated hemoglobin ≤7.0% is thought to reduce the microvascular and possibly macrovascular complications that result if T2DM is not properly managed. Recent guidelines have recognized the importance of postprandial glucose (PPG) control in reducing cardiovascular risks, and have recommended a more patient-centered approach. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) mimic the action of the endogenous gastrointestinal hormone GLP-1 to activate the insulin response in pancreatic beta cells in a glucose-dependent manner. Prandial GLP-1 RAs have a short plasma half-life and are particularly effective at targeting PPG elevations, whereas long-acting non-prandial GLP-1 RAs are more effective at reducing fasting plasma glucose. These differences highlight the potential for treatment with these agents to be tailored to the need of individual patients and their glycemic imbalance. All GLP-1 RAs are being evaluated in long-term cardiovascular outcome trials. To date, the only cardiovascular trial that has been completed is the ELIXA trial for lixisenatide, which was found to meet the pre-specified criterion of non-inferiority versus placebo in terms of cardiovascular outcomes.


The Influence of Psychological Factors on the Michigan Hand Questionnaire.
Background: Psychosocial factors help account for the gap between impairment and disability. This study examines the relationship between the Michigan Hand Questionnaire (MHQ) and commonly used psychological measures in patients with upper extremity illness. Methods: A cohort of 135 new or follow-up patients presenting to an urban academic hospital-based hand surgeon were invited to complete a web-based version of the MHQ, Abbreviated Pain Catastrophizing Scale (PCS), and two Patient-Reported Outcomes Measurement Information System (PROMIS)-based questionnaires: Pain Interference and Depression. Bivariate and multivariable analyses measured the correlation of these psychological measures with MHQ. Results: Accounting for potential confounding factors in multivariable regression, upper extremity disability as rated by the MHQ was independently associated with PROMIS Depression, PROMIS Pain Interference, visit type, and working status. The model accounted for 37% of the variability in MHQ scores, with PROMIS Pain Interference having the most influence. Conclusion: Among the non-pathophysiological factors that contribute to patient-to-patient variation in MHQ scores, the measure of less effective coping strategies and symptoms of depression were most influential. Our data add to the evidence of the pivotal role of emotional health in upper extremity symptoms and limitations and the importance of psychosocial considerations in the care of hand illness.