Training Package for Emergency Medical Teams Deployed to Disaster Stricken Areas: Has 'TEAMS' Achieved its Goals?
In spite of their good intentions, Emergency Medical Teams (EMTs) were relatively disorganized for many years. To enhance the efficient provision of EMT's field team work, the Training for Emergency Medical Teams and European Medical Corps (TEAMS) project was established. The purpose of this study was to assess the effectiveness and quality of the TEAMS training package in 2 pilot training programs in Germany and Turkey. A total of 19 German and 29 Turkish participants completed the TEAMS training package. Participants were asked to complete a set of questionnaires designed to assess self-efficacy, team work, and quality of training. The results suggest an improvement for both teams' self-efficacy and team work. The self-efficacy scale improved from 3.912 (± 0.655 SD) prior to training to 4.580 (± 0.369 SD) after training (out of 5). Team work improved from 3.085 (± 0.591 SD) to 3.556 (± 0.339 SD) (out of 4). The overall mean score of the quality of the training scale was 4.443 (± 0.671 SD) (out of 5). In conclusion, The TEAMS Training Package for Emergency Medical Teams has been demonstrated to be effective in promoting EMT team work capacities, and it is considered by its users to be a useful and appropriate tool for addressing their perceived needs.


Circ_0020123 promotes non-small cell lung cancer progression via miR-146a-5p mediated regulation of EIF4G2 expression.
Circular RNAs (circRNAs) have been reported to be involved in the initiation and development of cancers. The aim of this study was to determine the role of a circRNA, circ_0020123, in the development of non-small cell lung cancer (NSCLC). The expression of circ_0020123, microRNA-146a-5p (miR-146a-5p), and eukaryotic translation initiation factor 4 gamma 2 (EIF4G2) mRNA was detected by quantitative real-time PCR (qPCR). Western blot was used to determine the protein levels of cyclin D1, Bax, MMP-9, and EIF4G2. Cell proliferation was assessed by cell counting kit-8 (CCK-8) assay and colony formation assay. Flow cytometry assay was applied to determine cell cycle apoptosis. Cell migration and invasion were assessed using transwell assay. The potential relationship between miR-146a-5p and circ_0020123 or EIF4G2 was ascertained by dual-luciferase reporter assay and RIP assay. The role of circ_0020123 in vivo was explored by xenograft assay. Circ_0020123 was upregulated in NSCLC, and circ_0020123 knockdown repressed proliferation, migration, and invasion of NSCLC cells. Circ_0020123 targeted miR-146a-5p, and miR-146a-5p inhibitor reversed the effects of circ_0020123 knockdown on NSCLC cells. In addition, miR-146a-5p suppressed cell proliferation, migration, and invasion by targeting EIF4G2. Moreover, the antitumor role of circ_0020123 knockdown was verified in vivo. Knockdown of circ_0020123 inhibited NSCLC cell progression and tumor growth by targeting the miR-146a-5p/EIF4G2 axis.


The MHC class Ib protein ULBP1 is a nonredundant determinant of leukemia/lymphoma susceptibility to gammadelta T-cell cytotoxicity.
On the path to successful immunotherapy of hematopoietic tumors, gammadelta T cells offer great promise because of their human leukocyte antigen (HLA)-unrestricted targeting of a wide variety of leukemias/lymphomas. However, the molecular mechanisms underlying lymphoma recognition by gammadelta T cells remain unclear. Here we show that the expression levels of UL16-binding protein 1 (ULBP1) determine lymphoma susceptibility to gammadelta T cell-mediated cytolysis. Consistent with this, blockade of NKG2D, the receptor for ULBP1 expressed on all Vgamma9(+) T cells, significantly inhibits lymphoma cell killing. Specific loss-of-function studies demonstrate that the role of ULBP1 is nonredundant, highlighting a thus far unique physiologic relevance for tumor recognition by gammadelta T cells. Importantly, we observed a very wide spectrum of ULBP1 expression levels in primary biopsies obtained from lymphoma and leukemia patients. We suggest this will impact on the responsiveness to gammadelta T cell-based immunotherapy, and therefore propose ULBP1 to be used as a leukemia/lymphoma biomarker in upcoming clinical trials.


Indigenous compared with non-Indigenous Australian patients at entry to specialist palliative care: Cross-sectional findings from a multi-jurisdictional dataset.
There are few quantitative studies on palliative care provision to Indigenous Australians, a population known to experience distinctive barriers to quality healthcare and to have poorer health outcomes than other Australians. To investigate equity of specialist palliative care service provision through characterising and comparing Indigenous and non-Indigenous patients at entry to care. Using data (01/01/2010-30/06/2015) from all services participating in the multi-jurisdictional Palliative Care Outcomes Collaboration, Indigenous and non-Indigenous patients entering palliative care were compared on proportions vis-à-vis those expected from national statutory datasets, demographic characteristics, and entry-to-care status across fourteen 'problem' domains (e.g., pain, functional impairment) after matching by age, sex, and specific diagnosis. Of 140,267 patients, 1,465 (1.0%, much lower than expected from statutory data) were Indigenous, 133,987 (95.5%) non-Indigenous, and 4,905 (3.5%) had a missing identifier. The proportion of patients with a missing identifier diminished markedly over the study period, without a corresponding increase in the proportion identified as Indigenous. Indigenous compared with non-Indigenous patients were younger (mean 62.8 versus 73.0 years, p<0.001), a higher proportion were female (51.5% versus 46.3%; p<0.001) or resided outside major cities (44.2% versus 21.5%, p<0.001). Across all domains, Indigenous compared with matched non-Indigenous patients had lower or equal risk of status requiring prompt intervention. Indigenous patients (especially those residing outside major cities) are substantially under-represented in care by services participating in the nationwide specialist palliative care Collaboration, likely reflecting widespread access barriers. However, the similarity of status indicators among Indigenous and non-Indigenous patients at entry to care suggests that Indigenous patients who are able to access these services do not disproportionately experience clinically important impediments to care initiation.


Randomised controlled trial on robot-assisted versus manual surgery for pucker peeling.
The aim was to explore the feasibility and safety of performing common surgical steps in epiretinal membrane (ERM) peeling using the Preceyes Surgical System (PSS). In a tertiary centre, 15 pseudophakic patients with an idiopathic ERM were randomised to robot-assistance or manual surgery in a 2:1 ratio. In the robot-assisted group, the following steps were performed using PSS: (1) staining the internal limiting membrane (ILM), (2) removal of the dye, (3) creating an ILM flap, (4) completing the peeling, (5) holding a light pipe and (6) fluid-air exchange. Primary outcome measures were feasibility and safety. Secondary outcome measures were duration, best-corrected visual acuity (BCVA) and central retinal thickness (CRT). Moreover, the distance travelled by the instrument during peeling was assessed using motion tracking software. All steps performed with PSS were feasible with no clinical adverse events or complications. The surgical time was longer in the robot-assisted group (mean 56 min, SD = 12 vs. 24 min, SD = 5). During the study, the duration of robot-assisted surgeries decreased from 72 to 46 min. The distance travelled by the forceps was shorter in the robot-assisted group (mean 403 mm, SD = 186 vs. 550 mm, SD = 134). BCVA and CRT improved equally in both groups. This is the world's first randomised controlled trial on robotic surgery for ERM. Although more time-consuming, we found that several surgical steps were feasible with assistance of the PSS.


STARD 2015 guidelines for reporting diagnostic accuracy studies: explanation and elaboration.
Diagnostic accuracy studies are, like other clinical studies, at risk of bias due to shortcomings in design and conduct, and the results of a diagnostic accuracy study may not apply to other patient groups and settings. Readers of study reports need to be informed about study design and conduct, in sufficient detail to judge the trustworthiness and applicability of the study findings. The STARD statement (Standards for Reporting of Diagnostic Accuracy Studies) was developed to improve the completeness and transparency of reports of diagnostic accuracy studies. STARD contains a list of essential items that can be used as a checklist, by authors, reviewers and other readers, to ensure that a report of a diagnostic accuracy study contains the necessary information. STARD was recently updated. All updated STARD materials, including the checklist, are available at http://www.equator-network.org/reporting-guidelines/stard Here, we present the STARD 2015 explanation and elaboration document. Through commented examples of appropriate reporting, we clarify the rationale for each of the 30 items on the STARD 2015 checklist, and describe what is expected from authors in developing sufficiently informative study reports.


A Randomized Trial of Soft Multifocal Contact Lenses for Myopia Control: Baseline Data and Methods.
The Bifocal Lenses In Nearsighted Kids (BLINK) study is the first soft multifocal contact lens myopia control study to compare add powers and measure peripheral refractive error in the vertical meridian, so it will provide important information about the potential mechanism of myopia control. The BLINK study is a National Eye Institute-sponsored, double-masked, randomized clinical trial to investigate the effects of soft multifocal contact lenses on myopia progression. This article describes the subjects' baseline characteristics and study methods. Subjects were 7 to 11 years old, had -0.75 to -5.00 spherical component and less than 1.00 diopter (D) astigmatism, and had 20/25 or better logMAR distance visual acuity with manifest refraction in each eye and with +2.50-D add soft bifocal contact lenses on both eyes. Children were randomly assigned to wear Biofinity single-vision, Biofinity Multifocal "D" with a +1.50-D add power, or Biofinity Multifocal "D" with a +2.50-D add power contact lenses. We examined 443 subjects at the baseline visits, and 294 (66.4%) subjects were enrolled. Of the enrolled subjects, 177 (60.2%) were female, and 200 (68%) were white. The mean (± SD) age was 10.3 ± 1.2 years, and 117 (39.8%) of the eligible subjects were younger than 10 years. The mean spherical equivalent refractive error, measured by cycloplegic autorefraction was -2.39 ± 1.00 D. The best-corrected binocular logMAR visual acuity with glasses was +0.01 ± 0.06 (20/21) at distance and -0.03 ± 0.08 (20/18) at near. The BLINK study subjects are similar to patients who would routinely be eligible for myopia control in practice, so the results will provide clinical information about soft bifocal contact lens myopia control as well as information about the mechanism of the treatment effect, if one occurs.


The Effects of Galvanic Interactions with Pyrite on the Generation of Acid and Metalliferous Drainage.
Although the acid generating properties of pyrite (FeS2) have been studied extensively, the impact of galvanic interaction on pyrite oxidation, and the implications for acid and metalliferous drainage, remain largely unexplored. The relative galvanic effects on pyrite dissolution were found to be consistent with relative sulfide mineral surface area ratios with sphalerite (ZnS) having greater negative impact in batch leach tests (sulfide minerals only, controlled pH) and galena (PbS) having greater negative impact in kinetic leach column tests (KLCs, uncontrolled pH, >85 wt% silicate minerals). In contrast the presence of pyrite resulted consistently in greater increase in galena than sphalerite leaching suggesting that increased anodic leaching is dependent on the difference in anodic and cathodic sulfide mineral rest potentials. Acidity increases occurred after 44, 20, and 12 weeks in the pyrite-galena, pyrite-sphalerite, and the pyrite containing KLCs. Thereafter acid generation rates were similar with the Eh consistently above the rest potential of pyrite (660 mV, SHE). This suggests that treatment of waste rocks or tailings, to establish and maintain low Eh conditions, may help to sustain protective galvanic interactions and that monitoring of Eh of leachates is potentially a useful indicator for predicting changes in acid generation behavior.


Characterization of acid‑tolerance‑associated small RNAs in clinical isolates of Streptococcus mutans: Potential biomarkers for caries prevention.
Streptococcus mutans is a cariogenic bacterium that contributes to dental caries due to its ability to produce lactic acid, which acidifies the local environment. The potential of S. mutans to respond to environmental stress and tolerate low pH is essential for its survival and predominance in caries lesions. Small noncoding RNAs (sRNAs) have been reported to be involved in bacterial stress and virulence. Few studies have investigated the sRNAs of S. mutans and the function of these sRNAs remains to be elucidated. In the present study, the association between sRNA133474 and acid tolerance, including potential underlying mechanisms, were investigated within clinical strains of S. mutans. From pediatric dental plaques, 20 strains of S. mutans were isolated. An acid killing assay was performed to analyze acid tolerance of S. mutans. Expression patterns of sRNA133474 were investigated during various growth phases under various acidic conditions via reverse transcription‑quantitative polymerase chain reaction. RNA predator and Kyoto Encyclopedia of Genes and Genomes analyses were performed to predict target mRNAs of sRNA133474 and to examine the involvement of putative pathways of target mRNAs, respectively. The results of the present study demonstrated that sRNA133474 activity was growth phase‑dependent, and two distinct expression patterns were identified in 10 clinical strains. At pH 5.5 and 7.5 the expression levels of sRNA133474 were significantly different, and high‑acid tolerant strains exhibited reduced expression levels of sRNA133474 compared with low‑acid tolerant strains. A correlation between sRNA133474 expression levels and acid tolerance was observed in 20 clinical isolates of S. mutans (r=‑0.6298, P<0.01). Finally, five target mRNAs (liaS, liaR, comE, covR and ciaR) involved in the two‑component system (TCS) were selected for further evaluation; the expression levels of three target mRNAs (liaR, ciaR and covR) were negatively correlated with sRNA133474 expression levels. In conclusion, the results of the present study suggested that S. mutans may utilize sRNA133474 to orchestrate TCSs for optimal adaption to acidic pH in clinical strains.


Structural changes in the epidermal cells of Rhodnius during tracheole capture.
Epidermal cells deprived of their oxygen supply by tracheal section give off cytoplasmic processes which become attached to air-filled tracheoles in neighbouring areas and draw these into the oxygen-deficient zone. Many of these cytoplasmic strands exceed 100 micrometer in length but may be no more than 50 nm in diameter; they contain mitochondria, ribosomes, microtubules and microfilaments. In basis structure they resemble the tendon cells; and also the tapering conical epidermal cells along the intersegmental borders of the abdomen, the terminal strands of which are inserted into the basement memebrane behind and in front of the segmental boundaries. The cytoplasmic walls of those tracheoles most exposed to tension during the process of tracheole capture become thickened and packed with microtubules. In all these structures the microtubules are believed to be concerned in resistance to tension. Contraction is presumably effected by microfilaments, but no new evidence is given. The possible role of the epidermal strands in the transport of energy-rich metabolites is discussed.


A national US study of posttraumatic stress disorder, depression, and work and functional outcomes after hospitalization for traumatic injury.
To examine factors other than injury severity that are likely to influence functional outcomes after hospitalization for injury. This study used data from the National Study on the Costs and Outcomes of Trauma investigation to examine the association between posttraumatic stress disorder (PTSD), depression, and return to work and the development of functional impairments after injury. A total of 2707 surgical inpatients who were representative of 9374 injured patients were recruited from 69 hospitals across the US. PTSD and depression were assessed at 12 months postinjury, as were the following functional outcomes: activities of daily living, health status, and return to usual major activities and work. Regression analyses assessed the associations between PTSD and depression and functional outcomes while adjusting for clinical and demographic characteristics. At 12 months after injury, 20.7% of patients had PTSD and 6.6% had depression. Both disorders were independently associated with significant impairments across all functional outcomes. A dose-response relationship was observed, such that previously working patients with 1 disorder had a 3-fold increased odds of not returning to work 12 months after injury odds ratio = 3.20 95% (95% confidence interval = 2.46, 4.16), and patients with both disorders had a 5-6 fold increased odds of not returning to work after injury odds ratio = 5.57 (95% confidence interval = 2.51, 12.37) when compared with previously working patients without PTSD or depression. PTSD and depression occur frequently and are independently associated with enduring impairments after injury hospitalization. Early acute care interventions targeting these disorders have the potential to improve functional recovery after injury.


Intracerebral haemorrhage in previously healthy adults following aerobic and anaerobic exercise.
Intracerebral haemorrhage (ICH) without demonstrated tissue pathology in previously healthy adults has not been previously linked to anaerobic or aerobic exercise. The possible mechanisms and risk factors for ICH that may be found in a young, "healthy" adult are described. Case reports of two patients who suffered a frontal lobe ICH following aerobic and anaerobic exercise are presented. A review of the literature was carried out to elucidate the risk factors for ICH in previously healthy adults. Hypocholesterolemia below 4.14 mmol/l, phenylpropanolamine use above 75 mg per day and certain apolipoprotein phenotypes (Apo E2 and Apo E4), which can all be found in young, healthy adults have all been described in the literature as contributors to the risk of ICH. There is a need for these risk factors to be researched in more detail, given that potential risk modifiers may help decrease their posed threat.


Caffeine-induced physiological arousal accentuates global processing biases.
The effects of caffeine-induced arousal on global versus local object focus were investigated in non-habitual consumers using a double-blind, within-subjects, repeated-measures design. Following an overnight fast, low caffeine consumers (N=36; M=42.5mg/day caffeine) completed 5 counterbalanced test sessions (normal consumption, 0mg, 100mg, 200mg, and 400mg) separated by at least 3 days. During each session, volunteers either consumed their normal amount of caffeine or were administered 1 of 4 treatment pills. One hour later they completed two tasks assessing visual attention, in counterbalanced order. Measures of mood, salivary caffeine and cortisol were taken at multiple time points. Dose-dependent elevation of caffeine in the saliva demonstrated the experimental manipulation was effective. Furthermore, analyses of the mood and arousal measures detected consistent changes on arousal subscales and caffeine administration elevated saliva cortisol. Analyses of the visual attention tasks revealed that caffeine-induced physiological arousal produced global processing biases, after as little as 100mg caffeine. These data suggest caffeine consumption may influence how individuals attend to and process information in their environment and could influence daily tasks such as face recognition, learning new environments and navigation, especially for those who normally consume little caffeine.


Low Preoperative Mean Platelet Volume/Platelet Count Ratio Indicates Worse Prognosis in Non-Metastatic Renal Cell Carcinoma.
Multiple blood parameters are used to determine the prognosis of renal cell carcinoma (RCC). Mean platelet volume/platelet count (MPV/PC) ratio is related to disease progression in various cancers. Our study tried to evaluate the prognostic value of the MPV/PC ratio in RCC patients who underwent surgery. We retrospectively reviewed 89 patients who underwent radical or partial nephrectomy for RCC in a single institution. Baseline characteristics and MPV/PC ratios were analyzed. The optimal cut-off value of the MPV/PC ratio was determined by a receiver operating characteristic (ROC) curve, and our patients were divided into low and high MPV/PC ratio groups. The Kaplan-Meier survival curve and Cox proportional hazards model were applied for progression-free survival (PFS) and overall survival (OS) analyses. Harell's C-index was used to compare the prognostic values of the MPV/PC ratio, MPV and PC. Lower MPV/PC ratios were correlated with more advanced tumor stages and worse outcomes. The optimal cut-off value of the preoperative MPV/PC ratio was 0.034 (sensitivity 84.6%, specificity 56.6%). The Kaplan-Meier survival curve revealed that low MPV/PC ratios were associated with worse PFS (p = 0.007) and OS (p = 0.017). Multivariate analysis showed that low MPV/PC ratios were an independent unfavorable factor for PFS (p = 0.044) and OS (p = 0.015). Harell's C-indexes showed that the prognostic value of the MPV/PC ratio was significantly better than MPV and PC (p < 0.001). Low MPV/PC ratios are an independent, unfavorable risk factor for disease progression and overall survival in patients undergoing surgery for RCC.


Frequent and frequently overlooked: treatment-induced endocrine dysfunction in adult long-term survivors of primary brain tumors.
New treatments for primary brain tumors have improved survival but quality of life may be impaired by neuroendocrine dysfunction. We performed a controlled, cross-sectional study to assess frequency and clinical impact of endocrine dysfunction in adult long-term survivors of primary brain tumors outside the hypothalamic-pituitary region. Thirty-one patients (19 males and 12 females; age, 25 to 66 years) and 31 sex- and age-matched controls were studied 1.5 to 11 years after radiotherapy with a mean total dose of 62.3 +/- 2.8 Gy (mean local doses pituitary, 51.1 +/- 12.1 Gy; hypothalamus, 57.0 +/- 7.8 Gy). Structured clinical assessment included a standardized questionnaire. Thyroid, adrenal, and gonadal hormones were measured at baseline and, in the patients, also after stimulation. Sixteen patients (52%) reported two or more symptoms suggestive of hypothyroidism; eight patients (26%) showed evidence of hypothalamic hypothyroidism. Patients had significantly lower serum baseline concentrations of cortisol and dehydroepiandrosterone sulfate than controls, but no manifest hypoadrenalism was noticed except in one patient with panhypopituitarism. Forty-seven percent of the male patients, but only six percent of the controls, suffered from erectile dysfunction; 42% of the male patients showed either evidence of hypothalamic hypogonadism (32%) or primary gonadal damage (10%). Nine patients (29%) presented with hyperprolactinemia and four women concurrently suffered from oligo-amenorrhea. In adult patients treated for primary brain tumors, endocrine dysfunction due to radiation-induced hypothalamic damage is common and has a significant impact on well being. Endocrinologic evaluation should be performed periodically in these patients.


Implications of Long Non-Coding RNAs in Age-Altered Proteostasis.
This review aims to summarize the current knowledge on how lncRNAs are influencing aging and cancer metabolism. Recent research has shown that senescent cells re-enter cell-cycle depending on intrinsic or extrinsic factors, thus restoring tissue homeostasis in response to age-related diseases (ARDs). Furthermore, maintaining proteostasis or cellular protein homeostasis requires a correct quality control (QC) of protein synthesis, folding, conformational stability, and degradation. Long non-coding RNAs (lncRNAs), transcripts longer than 200 nucleotides, regulate gene expression through RNA-binding protein (RBP) interaction. Their association is linked to aging, an event of proteostasis collapse. The current review examines approaches that lead to recognition of senescence-associated lncRNAs, current methodologies, potential challenges that arise from studying these molecules, and their crucial implications in clinical practice.


Longitudinal associations of health-related behavior patterns in adolescence with change of weight status and self-rated health over a period of 6 years: results of the MoMo longitudinal study.
Promoting a healthy lifestyle especially in adolescents is important because health-related behaviors adopted during adolescence most often track into adulthood. Longitudinal studies are necessary for identifying health-related risk groups of adolescents and defining target groups for health-promoting interventions. Multiple health behavior research may represent a useful approach towards a better understanding of the complexity of health-related behavior. The aim of this study was to examine the longitudinal association of health-related behavior patterns with change of weight status and self-rated health in adolescents in Germany. Within the framework of the longitudinal German Health Interview and Examination Survey for Children and Adolescents (KiGGS) and the Motorik-Modul (MoMo), four clusters of typical health-related behavior patterns of adolescents have been previously identified. Therefor the variables 'physical activity', 'media use' and 'healthy nutrition' were included. In the current study longitudinal change of objectively measured weight status (N = 556) and self-rated health (N = 953) in the four clusters was examined. Statistical analyses comprised T-tests for paired samples, McNemar tests, multinomial logistic regression analysis and two-way ANOVA with repeated measures. The prevalence of overweight increased in all four clusters. The health-related behavior pattern of low activity level with high media use and low diet quality had the strongest increase in prevalence of overweight, while the smallest and non-significant increase was found with the behavior pattern of a high physical activity level and average media use and diet quality. Only some significant relationships between health-related behaviour patterns and change in self-rated health were observed. High-risk patterns of health-related behavior were identified. Further, cumulative as well as compensatory effects of different health-related behaviors on each other were found. The information gained in this study contributes to a better understanding of the complexity of health-related behavior and its impact on health parameters and may facilitate the development of targeted prevention programs.


The Relevance of Dietary Polyphenols in Cardiovascular Protection.
The chemical structure of polyphenols consisting of aromatic rings, capable of quenching free radicals, makes them ideal candidates to protect against oxidation. Polyphenols are present in a variety of foods including grapes, berries, dark chocolate, coffee and tea to mention a few. A number of studies have shown that dietary polyphenols exert a protective effect against hypertension, dyslipidemias, inflammation, endothelial function and atherosclerosis, conditions associated with increased risk for cardiovascular disease. Studies indicate that by decreasing cholesterol absorption, polyphenols alter hepatic cholesterol homeostasis resulting in decreases in plasma lipids and reduction in atherogenic lipoproteins thus having a protective effect against atherosclerosis; polyphenols have also been shown to decrease the activity of enzymes involved in the renin-angiotensinaldosterone system and improve blood pressure. Further, they have been recognized to increase nitric oxide production and to improve endothelial function. In this review we will present some of the evidence derived from epidemiological studies, clinical interventions as well as animal and cell studies supporting the cardioprotective effects of dietary polyphenols.


Hypertrophic cardiomyopathy with intermittent free mitral regurgitation-a surgical dilemma.
We describe the case of a 52-year-old woman presenting with non-ST elevation myocardial infarction, atrial fibrillation, and a new diagnosis of hypertrophic cardiomyopathy. Transesophageal echocardiography following hemodynamic deterioration revealed completely restricted mitral leaflet motion with free mitral regurgitation, and severe left ventricular outflow tract (LVOT) obstruction. Surgical intervention was considered; however, repeat imaging following a period of clinical stability revealed resolution of the findings suggesting a transient ischemic etiology. The case is supported by clinical and echocardiographic images with movie clips, and a discussion of the likely pathology in the context of the underlying condition.


Abutment region dosimetry for serial tomotherapy.
A commercial intensity modulated radiation therapy system (Corvus, NOMOS Corp.) is presently used in our clinic to generate optimized dose distributions delivered using a proprietary dynamic multileaf collimator (DMLC) (MIMiC) composed of 20 opposed leaf pairs. On our accelerator (Clinac 600C/D, Varian Associates, Inc.) each MIMiC leaf projects to either 1.00 x 0.84 or 1.00 x 1.70 cm2 (depending on the treatment plan and termed 1 cm or 2 cm mode, respectively). The MIMiC is used to deliver serial (axial) tomotherapy treatment plans, in which the beam is delivered to a nearly cylindrical volume as the DMLC is rotated about the patient. For longer targets, the patient is moved (indexed) between treatments a distance corresponding to the projected leaf width. The treatment relies on precise indexing and a method was developed to measure the precision of indexing devices. A treatment planning study of the dosimetric effects of incorrect patient indexing and concluded that a dose heterogeneity of 10% mm(-1) resulted. Because the results may be sensitive to the dose model accuracy, we conducted a measurement-based investigation of the consequences of incorrect indexing using our accelerator. Although the indexing provides an accurate field abutment along the isocenter, due to beam divergence, hot and cold spots will be produced below and above isocenter, respectively, when less than 300 degree arcs were used. A preliminary study recently determined that for a 290 degree rotation in 1 cm mode, 15% cold and 7% hot spots were delivered to 7 cm above and below isocenter, respectively. This study completes the earlier work by investigating the dose heterogeneity as a function of position relative to the axis of rotation, arc length, and leaf width. The influence of random daily patient positioning errors is also investigated. Treatment plans were generated using 8.0 cm diameter cylindrical target volumes within a homogeneous rectilinear film phantom. The plans included both 1 and 2 cm mode, optimized for 300 degrees, 240 degrees, and 180 degrees gantry rotations. Coronal-oriented films were irradiated throughout the target volumes and scanned using a laser film digitizer. The central target irradiated in 1 cm mode was also used to investigate the effects of incorrect couch indexing. The dose error as a function of couch index error was 25% mm(-1), significantly greater than previously reported. The clinically provided indexing system yielded 0.10 mm indexing precision. The intrinsic dose distributions indicated that more heterogeneous dose distributions resulted from the use of smaller gantry angle ranges and larger leaf projections. Using 300 degrees gantry angle and 1 cm mode yielded 7% hot and 15% cold spots 7 cm below and above isocenter, respectively. When a 180 degree gantry angle was used, the values changed to 22% hot and 27% cold spots for the same locations. The heterogeneities for the 2 cm mode were 70% greater than the corresponding 1 cm values. While serial tomotherapy is used to deliver highly conformal dose distributions, significant dosimetric factors must be considered before treatment. The patient must be immobilized during treatment to avoid dose heterogeneities caused by incorrect indexing due to patient movement. Even under ideal conditions, beam divergence can cause significant abutment-region dose heterogeneities. The use of larger gantry angle ranges, smaller leaf widths, and appropriate locations of the gantry rotation axis can minimize these effects.


On-site physicians reduce ambulance transports at mass gatherings.
To prospectively determine if on-site physicians at a mass gathering reduced the number of ambulance transports to local medical facilities. The authors also wished to determine the level of care provider (emergency medical technician, EMT-P, registered nurse, or medical doctor) required to treat and disposition each patient. This study determined whether each patient presenting to on-site first aid stations at California Speedway during a large motorsports event would require ambulance transport to the hospital per the local emergency medical services (EMS) protocols. Whether the on-site physician prevented certain ambulance transports also was determined. Additionally, the minimum level of provider that could treat and disposition each patient was determined. On-site physicians significantly reduced (p < 0.001) the number of ambulance transports at this mass gathering. Ambulance transports to local hospitals were reduced by 89% (from 116 to 13). Fifty-two percent of the patients were able to be treated and dispositioned (cardiac arrests, minor first aid, etc.) by a paramedic. Registered nurses were able to treat and disposition another 39% of the patients with pre-established protocols written by the track medical director. These patients had abrasions requiring tetanus shots, mild to moderate heat exhaustion that resolved with intravenous hydration, and other minor complaints. Finally, about 9% of the patients required physician-level care (suturing, prescriptions, etc.) to treat and disposition them. On-site physician-level medical care at large mass gatherings significantly reduces the number of patients requiring transport to hospitals, thus reducing the impact on the local EMS system and surrounding medical facilities.


Perinatal Transmission and Clinical Outcomes of Neonates Born to SARS-CoV-2-Positive Mothers.
The aim of the study was to investigate the clinical outcomes and rate of virus detection in neonates born to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive mothers. This prospective study included neonates born to SARS-CoV-2-positive mothers, documenting their viral polymerase chain reaction results and clinical outcomes. Of the 130 neonates born to 122 SARS-CoV-2-positive mothers, 12% tested positive. Most (62%) neonates were delivered via cesarean section at an average gestational age of 36 weeks, with a birth weight of 2,900 g. Only 38% neonates required admission. SARS-CoV-2-positive infants were born at a significantly lower gestational age; had a significantly lower birth weight; and had significantly higher admission rates, surfactant therapy, and bradycardia than SARS-CoV-2-negative infants. There was no significant difference in mortality rates. This study documents perinatal transmission of SARS-CoV-2. It reports for the first time the occurrence of neonatal bradycardia as a complication of maternal SARS-CoV-2 infection. Despite that, neonates born to SARS-CoV-2-positive mothers had relatively good short-term outcomes.


Clinicopathological, therapeutic and prognostic features of the triple-negative tumors in moroccan breast cancer patients (experience of Hassan II university hospital in Fez).
Triple-negative breast cancer (TNBC) is defined as a group of breast carcinomas that are negative for expression of hormone receptors (ER, PR) and Her2, we can distinguish between two groups: basal-like (ER-, PR-, Her2-, cytokeratin (CK) 5/6+ and/or Her1+) and unclassified subtype (ER-, PR-, Her2-, Her1- and CK5/6-).The aim of this study is to determine the clinicopathological, histological, therapeutic and prognostic features associated with this type of breast cancer. This is a retrospective study of 366 female breast cancer patients, diagnosed between January 2007 and June 2010 at the Department of Pathology. Epidemiological, clinical, histological, therapeutic and evolutive data were analyzed. OS and DFS rates were estimated by Kaplan-Meier analysis and a log-rank test to estimate outcome. A total of 64 women were identified as having TNBC (17.5% of all female breast cancer patients), 12.6% were basal-like, 4.9% were unclassified subtype, with a median age of 45 years. The median histological tumor diameter was 4.3 cm. TNBC were most often associated with a high grade, 49.2% grade III (53% for unclassified subtype, 47.6% for basal-like). Vascular invasion was found in 26.6% of cases (22% for unclassified subtype and 28.3% for basal-like). For the lymph node involvement: 51% had positive lymph nodes, and 22.4% had distant metastases. Neoadjuvant chemotherapy was administered to 18% patients with 26% of complete pathologic response; therefore adjuvant chemotherapy was given to 82%. 98% received anthracycline based regimen and only 30% received taxanes.The Kaplan-Meier curves based showed the lowest survival probability at 3-years (49% of OS, and 39% of DFS). TNBC is associated with young age, high grade tumors, advanced stage at diagnosis, difference chemo response compared to other subtypes, and shortest survival. Critical to optimal future management is accurate identification of truly triple negative disease, and adequately powered prospective TNBC trials to establish treatment efficacy and define predictive biomarkers.


Psychometric evaluation of the Spanish version of the Pediatric Quality of Life Eosinophilic Esophagitis Questionnaire (Peds QL-EoE Module ™).
The Paediatric Eosinophilic Oesophagitis Module (PedsQL-EoE) was developed in English as a valid and reliable questionnaire to assess health-related quality of life (HRQoL) in children with EoE. The aim of this study was to evaluate the validity and reliability of the PedsQL-EoE that was previously adapted to Spanish by our group. This cross-sectional multicentre study was conducted in 36 paediatric gastroenterology units. Groups with and without dietary restrictions were studied separately. The PedsQL-EoE consists of 33 items divided into seven factors. Age-specific versions of the PedsQL-EoE were sent by e-mail to children and parents. Statistical analysis was used to study the questionnaire structure by means of exploratory factor analysis and interitem correlations. Confirmatory factor analysis (CFA) was applied to verify the proposed model as well as its psychometric properties through SMSR (standardized root mean square), outer loadings and R-square. To study construct validity and reliability, Cronbach´s alpha coefficient, convergent validity (AVE), discriminant validity (HTMT) and intraclass correlation coefficients (ICC) were used. A total of 341 children and 394 parents participated with 307 matched answers. The median age was 12 years, and 75% were male. The questionnaire structure explained 68% and 66% of the total variance for parents and children, respectively. Five items showed negative correlations and were removed from the questionnaire. CFA applied to the new model supported the following construct: SMRS was less than 0.08, outer loadings measured above 0.5, and R2 explained more than 89% of the total variance. Once the modifications were performed, good internal consistency was demonstrated, with Cronbach's alpha values > 0.7, AVE values > 0.5 and HTMT < 0.9 with good child/parent agreement (ICC = 0.80). The most robust model of the PedsQL-EoE module was formed by seven factors: Symptoms I (6 items), Symptoms II (4 items), Treatment (4 items), Worries (3 items), Communication (5 items), Food and Eating (3 items) and Food Feelings (3 items). The final PedsQL-EoE Module version, after the removal of five items, is a valid and reliable tool to be used in children with EoE. The Spanish validated version appears to be a useful instrument for measuring the impact of EoE on Spanish children´s quality of life.


Measuring Orthorexia Nervosa: Psychometric Limitations of the ORTO-15.
Orthorexia nervosa has recently been defined as excessive preoccupation with healthy eating, causing significant nutritional deficiencies and social and personal impairments. The ORTO-15 is the most widely used instrument to evaluate orthorexia nervosa, although previous studies obtained inconsistent results about its psychometric properties, and there are no data on the Spanish version. Thus, the main objective of the present study was to analyze the psychometric properties of the Spanish adaptation of the ORTO-15. In order to cross-validate the results, two independent samples were used (Sample 1: n = 807, 74.1% women; Sample 2: n = 242, 63.2% women). The results did not support the original recoding and reversal of the items; thus, the original scores were maintained. The analysis of the internal structure showed that the best interpretable solution was unidimensional, and due to low loadings, four items were removed. The internal consistency (α = .74) and temporal stability (r = .92; p < .001) of the final ORTO-11 version were adequate, higher than the 15-item version. The questionnaire showed significant associations with eating psychopathology (EAT-26 and SR-YBC-EDS; range r = .64 - .29; p < .05). However, this result should be interpreted with caution due to the redundancy observed between the ORTO-15 and the EAT-26. Our results suggest that the psychometric properties of the Spanish version of the ORTO-15 are not adequate. Moreover, the instrument detects people who are on diets, but it is not efficient in detecting the severity of orthorexic behaviors and attitudes. New instruments are needed to continue the study of orthorexia nervosa.


PTSD is negatively associated with physical performance and physical function in older overweight military Veterans.
This study examines the effect of posttraumatic stress disorder (PTSD) on function and physical performance in older overweight military Veterans with comorbid conditions. This is a secondary data analysis of older Veterans (mean age = 62.9 yr) participating in a physical activity counseling trial. Study participants with PTSD (n = 67) and without PTSD (n = 235) were identified. Self-reported physical function (36-item Short Form Health Survey) and directly measured physical performance (mobility, aerobic endurance, strength) were assessed. Multivariate analyses of variance controlling for demographic factors and psychiatric disorders demonstrated significant physical impairment among those with PTSD. PTSD was negatively associated with self-reported physical function, functioning in daily activities, and general health (p < 0.01). Those with PTSD also performed significantly worse on tests of lower-limb function (p < 0.05). Despite being significantly younger, Veterans with PTSD had comparable scores on gait speed, aerobic endurance, grip strength, and bodily pain compared with Veterans without PTSD. This study provides preliminary data for the negative association between PTSD and physical function in older military Veterans. These data highlight the importance of ongoing monitoring of physical performance among returning Veterans with PTSD and intervening in older overweight Veterans with PTSD, whose physical performance scores are indicative of accelerated risk of premature functional aging.


Integrity: is it still relevant to modern healthcare?
Personal integrity is often seen as a core value for delivering ethical healthcare. This paper will explore what this might mean and particularly what place integrity has in a multi-professional healthcare system. Two opposing arguments can be made: the first is that the multi-professional nature of modern healthcare means that personal integrity is at best a futile luxury and at worst, an obstacle to delivering affordable high-quality care to large populations. The converse is that without personal integrity healthcare loses its humanity and becomes mere biological and social engineering. Part of the analysis rests on whether integrity is primarily a personally held moral framework or whether it is a social concept. Chester Calhoun's analysis, in which she identifies the integrated-self, personal identity, and (morally) clean-hands as three pictures of integrity, is used as the basis for suggesting that integrity is a rich and complex social virtue through which the individual is able to demonstrate their relationship with the values and mores of the communities of which they are members. In addition, I will argue that integrity is not a value itself, but is a framework through which one or more sets of those values that characterize the communities of which the person is a part, can be expressed. Because a person may belong to many communities - nation, gender, religion, family, profession, trade, sport, etc. - each individual has their own unique meta-set of values that informs their personal sense of integrity. However, in specific circumstances, conflicts may arise between this personal global sense and the set of values associated with one community.


Genetic Profiling of Aggregatibacter actinomycetemcomitans Serotype B Isolated from Periodontitis Patients Living in Sweden.
The bacterium Aggregatibacter actinomycetemcomitans is associated with aggressive forms of periodontitis and with systemic diseases, such as endocarditis. By assessing a Ghanaian longitudinal adolescent cohort, we earlier recognized the cagE gene as a possible diagnostic marker for a subgroup of JP2 and non-JP2 genotype serotype b A. actinomycetemcomitans strains, associated with high leukotoxicity as determined in a semi-quantitative cell assay. This group of A. actinomycetemcomitans is associated with the progression of attachment loss. In the present work, we used conventional polymerase chain reaction (PCR) and quantitative PCR to perform the cagE genotyping of our collection of 116 selected serotype b A. actinomycetemcomitans strains, collected over a period of 15 years from periodontitis patients living in Sweden. The A. actinomycetemcomitans strains carrying cagE (referred to as cagE+; n = 49) were compared to the cagE-negative strains (n = 67), present at larger proportions in the subgingival plaque samples, and were also much more prevalent in the young (≤35 years) compared to in the old (>35 years) group of patients. Our present results underline the potential use of cagE genotyping in the risk assessment of the development of periodontal attachment loss in Swedish adolescents.


Inhibitory Effect of Damulin B from Gynostemma pentaphyllum on Human Lung Cancer Cells.
Damulin B, a dammarane-type saponin from steamed Gynostemma pentaphyllum, exhibits the strongest activity against human lung carcinoma A549 cells among the isolated active saponins. In this study, the structure-activity relationship of a series of saponin compounds was discussed. The inhibitory effect of damulin B on human lung cancer A549 and H1299 cells was investigated from apoptosis, cell cycle, and migration aspects. In vitro, human lung cancer cells were more susceptible to damulin B treatment than human normal fibroblasts. Damulin B exhibited a strong cytotoxic effect, as evidenced by the increase of apoptosis rate, reduction of mitochondrial membrane potential (MMP), generation of reactive oxygen species, and G0/G1 phase arrest. Furthermore, damulin B activated the following: both intrinsic and extrinsic apoptosis pathways along with early G1 phase arrest via the upregulation of the Bax, Bid, tBid, cleaved caspase-8, and p53 expression levels; downregulation of the procaspase-8/-9, CDK4, CDK6, and cyclin D1 expression levels; and more release of cytochrome c in the cytoplasm. In addition, antimigratory activities and suppressive effects on metastasis-related factors, such as MMP-2 and MMP-9, accompanied by the upregulation of IL-24 were revealed. Altogether, the results proved that damulin B could inhibit human lung cancer cells by inducing apoptosis, blocking the cell cycle at early G0/G1 phase and suppressing the migration. Hence, damulin B has potential therapeutic efficacy against lung cancer.


Efficacy of exercise for menopausal symptoms: a randomized controlled trial.
This study aims to determine the efficacy of exercise training for alleviating vasomotor and other menopausal symptoms. Late perimenopausal and postmenopausal sedentary women with frequent vasomotor symptoms (VMS) participated in a randomized controlled trial conducted in three sites: 106 women randomized to exercise and 142 women randomized to usual activity. The exercise intervention consisted of individual facility-based aerobic exercise training three times per week for 12 weeks. VMS frequency and bother were recorded on daily diaries at baseline and on weeks 6 and 12. Intent-to-treat analyses compared between-group differences in changes in VMS frequency and bother, sleep symptoms (Insomnia Severity Index and Pittsburgh Sleep Quality Index), and mood (Patient Health Questionnaire-8 and Generalized Anxiety Disorder-7 questionnaire). At the end of week 12, changes in VMS frequency in the exercise group (mean change, -2.4 VMS/d; 95% CI, -3.0 to -1.7) and VMS bother (mean change on a four-point scale, -0.5; 95% CI, -0.6 to -0.4) were not significantly different from those in the control group (-2.6 VMS/d; 95% CI, -3.2 to -2.0; P = 0.43; -0.5 points; 95% CI, -0.6 to -0.4; P = 0.75). The exercise group reported greater improvement in insomnia symptoms (P = 0.03), subjective sleep quality (P = 0.01), and depressive symptoms (P = 0.04), but differences were small and not statistically significant when P values were adjusted for multiple comparisons. Results were similar when considering treatment-adherent women only. These findings provide strong evidence that 12 weeks of moderate-intensity aerobic exercise do not alleviate VMS but may result in small improvements in sleep quality, insomnia, and depression in midlife sedentary women.


Using musculoskeletal modeling to evaluate the effect of ankle foot orthosis tuning on musculotendon dynamics: a case study.
This case study examines the influence of an ankle foot orthosis footwear combination (AFO-FC) on musculotendon lengths and gait kinematics and kinetics after right thrombotic stroke resulting in left hemiplegia. Gait analysis was performed over three visits where the subject walked with an AFO-FC with two shank-to-vertical angle (SVA) alignments, a posterior leaf spring AFO (PLS AFO), and shoes alone. Biomechanical and musculoskeletal modeling was used to evaluate musculotendon lengths, kinematics, and kinetics for each condition. The AFO-FC improved walking speed and non-paretic kinematics compared to the PLS AFO and shoes alone. The operating length of the paretic gastrocnemius decreased with the AFO-FC improving knee kinematics in swing, but not stance. As the SVA of the AFO-FC was reduced from 15° to 12°, internal ankle plantar flexor moment increased. Musculoskeletal modeling demonstrated that the AFO-FC altered gastrocnemius operating length during post-stroke hemiplegic gait. Using these tools to evaluate muscle operating lengths can provide insight into underlying mechanisms that may improve gait and guide future AFO-FC design. Implications for Rehabilitation Modeling musculotendon operating lengths during movement has the potential to inform how ankle foot orthoses (AFO) affect tight muscles and improve mobility after stroke. Adjusting shank-to-vertical angle (SVA) of the AFO-footwear combination (AFO-FC) has the potential to improve gait kinematics by controlling length of the pathologic gastrocnemius and maximizing internal ankle plantar flexor moment of individuals with neuromuscular disorders.


[Morphologic changes in the nervous system in acute carbophos poisoning].
The nervous system of 13 patients who died of an acute oral intoxication with carbophos was subjected to morphological examinations. Vascular changes were expressed as congestive plethora, perivascular edema and microfocal hemorrhages. Cellular abnormalities mainly included acute swelling, severe ischemic and hydropic alterations. Pathomorphology of the fibers was manifested in foci of secondary demyelinization in the internal capsule, lateral columns of the spinal cord and the peripheral nerves of the extremities.


The Double Burden of Malnutrition and Associated Factors among South Asian Adolescents: Findings from the Global School-Based Student Health Survey.
The health and nutrition of the global adolescent population have been under-researched, in spite of its significant size (1.2 billion). This study investigates the prevalence and associated factors of malnutrition (stunting, thinness and overweight) among adolescents living in South Asia. The sample analysed was 24,053 South Asian schooled adolescents aged 12-15 years that participated in the cross-sectional Global School-Based Student Health Survey (GSHS) between 2009 and 2016. The prevalence of stunting, thinness and overweight was calculated using the World Health Organization (WHO) Child Growth Reference 2007. Associations between the three forms of malnutrition and their possible associated factors were assessed with binary logistic regression analysis using bootstrapping as a resampling method. The overall prevalence of stunting in South Asia was 13%, thinness was 10.8% and overweight was 10.8%. In the logistic regression model of the overall pooled sample, the factors associated with adolescent malnutrition were: age, hygiene behaviours, social support, sedentary behaviour, and tobacco use. A substantial proportion of stunting, thinness and overweight was found among school-going South Asian adolescents, indicating that the double burden of malnutrition is present in this population. Future research should seek to further understand the relationship between all forms of malnutrition and its associated factors in the adolescent population.


Epigenetic control of hematopoietic stem cell aging the case of Ezh2.
Hematopoietic stem cells have potent, but not unlimited, selfrenewal potential. The mechanisms that restrict selfrenewal are likely to play a role during aging. Recent data suggest that the regulation of histone modifications by Polycomb group genes may be of crucial relevance to balance selfrenewal and aging. We provide evidence for the involvement of one of these Polycomb group genes, Ezh2, in aging of the hematopoietic stem cell system.


Inhibiting tau-induced elevated nSMase2 activity and ceramides is therapeutic in murine Alzheimer's disease.
Cognitive decline in Alzheimer's disease (AD) is associated with prion-like tau propagation between neurons along synaptically connected networks, in part via extracellular vesicles (EV). EV biogenesis is triggered by ceramide enrichment at the plasma membrane from neutral sphingomyelinase2(nSMase2)-mediated cleavage of sphingomyelin. We report, for the first time, that tau expression triggers an elevation in brain ceramides and nSMase2 activity. To determine the therapeutic benefit of inhibiting this elevation, we evaluated the efficacy of PDDC, the first potent, selective, orally bioavailable, and brain-penetrable nSMase2 inhibitor, in the PS19 tau transgenic AD murine model. Changes in brain ceramide and sphingomyelin levels, Tau content, histopathology, and nSMase2 target engagement were monitored, as well as changes in the number of brain-derived EVs in plasma and their Tau content. Additionally, we evaluated the ability of PDDC to impede tau propagation in a murine model where an adeno-associated virus(AAV) encoding for P301L/S320F double mutant human tau was stereotaxically-injected unilaterally into the hippocampus and the contralateral transfer to the dentate gyrus was monitored. Similar to human AD, PS19 mice exhibited increased brain ceramides and nSMase2 activity; both were completely normalized by PDDC treatment. PS19 mice exhibited elevated tau immunostaining, thinning of hippocampal neuronal cell layers, increased mossy fiber synaptophysin immunostaining, and glial activation, all pathologic features of human AD. PDDC treatment significantly attenuated these aberrant changes. Mouse plasma isolated from PDDC-treated PS19 mice exhibited reduced levels of neuron- and microglia-derived EVs, the former carrying lower phosphorylated Tau(pTau) levels, compared to untreated mice. In the AAV tau propagation model, PDDC normalized the tau-induced increase in brain ceramides and significantly decreased tau spreading to the contralateral side. PDDC is a first-in-class therapeutic candidate that normalizes elevated brain ceramides and nSMase2 activity leading to the slowing of tau spread in AD mice.


Bilateral Poorly Differentiated Adenocarcinoma of the Lacrimal Gland With Tumor Regression After Treatment With Pembrolizumab.
An 85-year-old man presented with a 6-month history of worsening left proptosis and painless ophthalmoplegia. Imaging revealed an extensive intraconal and extraconal tumor extending to the level of the optic foramen, as well as the scalp, cheek, and the nasal bridge. Incisional biopsy was consistent with lacrimal gland adenocarcinoma. The patient underwent a left orbital exenteration followed by immunotherapy with pembrolizumab. The treatment was stopped prematurely after 5 cycles due to development of autoimmune colitis. Four months later, the patient developed new contralateral disease in the right orbit and an incisional biopsy again showed lacrimal gland adenocarcinoma. Following the incisional biopsy, no further treatment was administered, but over the ensuing 6 months, there was dramatic spontaneous regression of the tumor both clinically and radiographically. At 28 months, the patient is still alive with relatively stable disease.


Targeting ribonucleotide reductase for cancer therapy.
Ribonucleotide reductase (RR) is a unique enzyme, because it is responsible for reducing ribonucleotides to their corresponding deoxyribonucleotides, which are the building blocks required for DNA replication and repair. Dysregulated RR activity is associated with genomic instability, malignant transformation and cancer development. The use of RR inhibitors, either as a single agent or combined with other therapies, has proven to be a promising approach for treating solid tumors and hematological malignancies. This review covers recent publications in the area of RR, which include: i) the structure, function and regulation of RR; ii) the roles of RR in cancer development; iii) the classification, mechanisms and clinical application of RR inhibitors for cancer therapy and iv) strategies for developing novel RR inhibitors in the future. Exploring the possible nonenzymatic roles of RR subunit proteins in carcinogenesis may lead to new rationales for developing novel anticancer drugs. Updated information about the structure and holoenzyme models of RR will help in identifying potential sites in the protein that could be targets for novel RR inhibitors. Determining RR activity and subunit levels in clinical samples will provide a rational platform for developing personalized cancer therapies that use RR inhibitors.


Equivocal notions of accuracy and genetic screening of the general population.
The explosive growth in genetic technology quickly will make possible an unprecedented number of tests for genetically based conditions. A necessary condition for the use of such tests without risk of harm to the patient is their accuracy. However, most discussions of test accuracy in the literature have equivocated between two importantly different meanings of the word. In particular, it must be remembered that a high analytic accuracy does not imply a high diagnostic accuracy. Questions about the diagnostic accuracy of genetic tests presently loom large because of our limited knowledge of the complex etiology of disease and the distribution within the general population of the causal factors involved. Our current inability to supply patients with accurate diagnosis based on genetic information, however, is less problematic when examined in the context of new reproductive technologies such as in vitro fertilization and intraplasmic sperm injection.


Adherent primary cultures of mouse intercostal muscle fibers for isolated fiber studies.
Primary culture models of single adult skeletal muscle fibers dissociated from locomotor muscles adhered to glass coverslips are routine and allow monitoring of functional processes in living cultured fibers. To date, such isolated fiber cultures have not been established for respiratory muscles, despite the fact that dysfunction of core respiratory muscles leading to respiratory arrest is the most common cause of death in many muscular diseases. Here we present the first description of an adherent culture system for single adult intercostal muscle fibers from the adult mouse. This system allows for monitoring functional properties of these living muscle fibers in culture with or without electrical field stimulation to drive muscle fiber contraction at physiological or pathological respiratory firing patterns. We also provide initial characterization of these fibers, demonstrating several common techniques in this new model system in the context of the established Flexor Digitorum Brevis muscle primary culture model.


Hypochlorite injury of Clostridium botulinum spores alters germination responses.
Clostridium botulinum spores were sublethally damaged by exposure to 12 or 28 micrograms of available chlorine per ml for 2 min at 25 degrees C and pH 7.0. The damaging dose was 2.7 x 10(-6) to 3.1 x 10(-6) micrograms of available chlorine per spore. Damage was manifested by a consistent 1.6 to 2.4 log difference between the most probable number enumeration of spores (modified peptone colloid medium) and the colony count (modified peptone yeast extract glucose agar); this did not occur with control spores. Damaged spores could be enumerated by the colony count procedure. Germination responses were measured in several defined and nondefined media. Hypochlorite treatment altered the rate and extent of germination in some of the media. Calcium lactate (9 mM) permitted L-alanine (4.5 mM) germination of hypochlorite-treated spores in a medium containing 12 or 55 mM sodium bicarbonate, 0.8 mM sodium thiosulfate, and 100 mM Tris-hydrochloride (pH 7.0) buffer. Tryptose inhibited L-alanine germination of the spores. Treatments with hypochlorite and with hydrogen peroxide (7%, 25 degrees C, 2 min) caused similar enumeration and germination responses, indicating that the effect was due to a general oxidation phenomenon.


Xotx5b, a new member of the Otx gene family, may be involved in anterior and eye development in Xenopus laevis.
We describe the cloning, expression pattern and functional overexpression analysis of Xotx5b, a new member of the Otx gene family in Xenopus laevis. Early expression of Xotx5b resembles that of Xotx2, being detected in the organizer region at early gastrula stage, and, shortly after, also in anterior neuroectoderm. During neurula stages Xotx5b exhibits a changing and dynamic pattern of expression. After neural tube closure, Xotx5b is expressed in the eye and pineal gland, both involved in photoreception. Overexpression of Xotx5b has a similar effect to that of Xotx2, producing posterior truncations and inducing ectopic cement gland and neural tissue in whole embryos. In animal cap assays, Xotx5b and Xotx2 are both able to activate XAG, to strongly suppress the expression of the epidermal marker XK81, and to reciprocally activate each other. Finally, in einsteck transplantation assays, Xotx5b is able to respecify a tail/trunk organizer to a head organizer.


The relation between audition and vision in the human newborn.
Four studies were conducted to investigate the relation between audition and vision in the human newborn. In all four studies visual activity was recorded with infrared corneal-reflection technqiues in 1- to 4-day-old infants. Study 1 concerned the effects of sound at midline on scanning in darkness and in a lit but formless field. In the dark compared to light, newborns maintained better eye control, centralized fixations, scanned with smaller eye movements, scanned less dispersely, and were wider-eyed. In a blank field, sound caused newborns to maintain better eye control, centralize fixations, scan with small eye movements, constrain fixations, and be wider-eyed than in silence. Sound had little effect on scanning in the dark beyond constraining fixations. Study 2 concerned the effects of sound at midline on scanning vertical and horizontal edges. Visual activity was different for the two visual stimuli. While viewing a vertical rather than a horizontal edge, newborns maintained better eye control and fixated closer to the position of the vertical edge. Newborns crossed the position of the horizontal edge when that edge was present. Sound affected scanning in general, centralizing fixations for newborns not already looking centrally, but sound did not affect the frequency of edge crossing. Study 3 concerned the effects of laterally presented sound on scanning spatially consonant or dissonant vertical bars. The major finding was that infants were sensitive to the spatial property of sound. Infants shifted fixations first toward and then gradually away from sound. Study 4 was an attempt to determine whether there is an effort constraint on the simultaneous functioning of auditory and visual systems. The effects of two differentially salient sounds on scanning two differentially salient visual stimuli were examined. Although the results appeared to support the idea of an effort constraint, the data were accounted for parsimoniously in terms of the spatial influence of sound of scanning. The data on visual activity were discussed in terms of the presence of inherent information-acquisition routines in the newborn. It was concluded that sound influences visual epistemic behavior even at birth.


gamma-Aminobutyric acid directly depolarizes cultured oligodendrocytes.
gamma-Aminobutyric acid (GABA) depolarizes in a dose-dependent manner approximately one-third of all immunologically identified oligodendrocytes in cultures of mouse spinal cord. Measurements of [K+]o indicate that the response to GABA is not due to K+ released from active neurons. The depolarization is not accompanied by a change in cell input resistance. Replacement of sodium in the bathing solution abolishes the entire response, whereas ouabain only inhibits the repolarization phase. Current clamp experiments with two separate intracellular electrodes show that the depolarization increases at more positive potentials while the repolarization increases at more negative potentials. Bicuculline and picrotoxin but not nipecotic acid reduce the GABA effect. Pentobarbital and chlordiazepoxid also reduce the GABA-induced depolarization. Muscimol produces a depolarization similar to that of GABA. Heterogeneity in the oligodendrocyte population is indicated by the observation that some cells respond to both GABA and glutamate, while others respond only to one and some are not responsive to either.


Inhibitor mechanisms in the S1 binding site of the dopamine transporter defined by multi-site molecular tethering of photoactive cocaine analogs.
Dopamine transporter (DAT) blockers like cocaine and many other abused and therapeutic drugs bind and stabilize an inactive form of the transporter inhibiting reuptake of extracellular dopamine (DA). The resulting increases in DA lead to the ability of these drugs to induce psychomotor alterations and addiction, but paradoxical findings in animal models indicate that not all DAT antagonists induce cocaine-like behavioral outcomes. How this occurs is not known, but one possibility is that uptake inhibitors may bind at multiple locations or in different poses to stabilize distinct conformational transporter states associated with differential neurochemical endpoints. Understanding the molecular mechanisms governing the pharmacological inhibition of DAT is therefore key for understanding the requisite interactions for behavioral modulation and addiction. Previously, we leveraged complementary computational docking, mutagenesis, peptide mapping, and substituted cysteine accessibility strategies to identify the specific adduction site and binding pose for the crosslinkable, photoactive cocaine analog, RTI 82, which contains a photoactive azide attached at the 2β position of the tropane pharmacophore. Here, we utilize similar methodology with a different cocaine analog N-[4-(4-azido-3-I-iodophenyl)-butyl]-2-carbomethoxy-3-(4-chlorophenyl)tropane, MFZ 2-24, where the photoactive azide is attached to the tropane nitrogen. In contrast to RTI 82, which crosslinked into residue Phe319 of transmembrane domain (TM) 6, our findings show that MFZ 2-24 adducts to Leu80 in TM1 with modeling and biochemical data indicating that MFZ 2-24, like RTI 82, occupies the central S1 binding pocket with the (+)-charged tropane ring nitrogen coordinating with the (-)-charged carboxyl side chain of Asp79. The superimposition of the tropane ring in the three-dimensional binding poses of these two distinct ligands provides strong experimental evidence for cocaine binding to DAT in the S1 site and the importance of the tropane moiety in competitive mechanisms of DA uptake inhibition. These findings set a structure-function baseline for comparison of typical and atypical DAT inhibitors and how their interactions with DAT could lead to the loss of cocaine-like behaviors.


Ligand-independent exhaustion of killer immunoglobulin-like receptor-positive CD8+ T cells in human immunodeficiency virus type 1 infection.
Virus-specific CD8(+) T cells play a central role in the control of viral infections, including human immunodeficiency virus type 1 (HIV-1) infection. However, despite the presence of strong and broad HIV-specific CD8(+) T-cell responses in chronic HIV-1 infection, these cells progressively lose critical effector functions and fail to clear the infection. Mounting evidence suggests that the upregulation of several inhibitory regulatory receptors on the surface of CD8(+) T cells during HIV-1 infection may contribute directly to the impairment of T-cell function. Here, we investigated the role of killer immunoglobulin receptors (KIR), which are expressed on NK cells and on CD8(+) T cells, in regulating CD8(+) T-cell function in HIV-1 infection. KIR expression was progressively upregulated on CD8(+) T cells during HIV-1 infection and correlated with the level of viral replication. Expression of KIR was associated with a profound inhibition of cytokine secretion, degranulation, proliferation, and activation by CD8(+) T cells following stimulation with T-cell receptor (TCR)-dependent stimuli. In contrast, KIR(+) CD8(+) T cells responded potently to TCR-independent stimulation, demonstrating that these cells are functionally competent. KIR-associated suppression of CD8(+) T-cell function was independent of ligand engagement, suggesting that these regulatory receptors may constitutively repress TCR activation. This ligand-independent repression of TCR activation of KIR(+) CD8(+) T cells may represent a significant barrier to therapeutic interventions aimed at improving the quality of the HIV-specific CD8(+) T-cell response in infected individuals.


Recent Nanoscale Carriers for Therapy of Alzheimer's Disease: Current Strategies and Perspectives.
This review covers nanotherapeutic strategies for solving the global problems associated with Alzheimer's disease (AD). The most dramatic factor contributing humanistic, social and economic urgency of the situation is the incurability of the disease, with the drug intervention addressing only AD symptoms and retarding their progress. Key sources behind these challenges are the inability of the early diagnosis of AD, the lack of comprehensive information on the molecular mechanism of the pathogenesis, the bloodbrain barrier obstacles, and the insufficient effectiveness of currently available drugs and therapeutic strategies. The application of nanocarriers allows part of these problems to be solved, together with the improvement of drug bioavailability, prolonged circulation, and overcoming/bypassing the biological barriers. To this date, numerous types and subtypes of nanocarriers are developed and reviewed, the majority of which can be adapted for the treatment of various diseases. Therefore, herein, nanotherapy strategies are specifically categorized in term of the administration routes of AD medicines, with the noninvasive, i.e., transdermal, oral, and intranasal routes emphasized. Further, benefits/ limitations of various nanocarriers are discussed, and perspectives of their application are highlighted.


The Same Angiographic Factors Predict Venous and Arterial Graft Patency: A Retrospective Study.
To evaluate the value of angiographic factors in predicting failure of both venous and arterial coronary artery bypass graft. We retrieved from our angiographic database 148 patients who underwent venous and/or arterial CABG and for whom a control coronary angiography at more than 1 month after surgery was available. Pre-CABG and follow-up angiographies were analyzed in order to evaluate diameter stenosis (DS,%), stenosis length (mm), Bogaty score (extent index), Sullivan score, and Gensini score for the extent of coronary artery disease, and Jeopardy Duke score for the extent of myocardial area supplied by an artery. Thirty-nine patients (26%) experienced graft failure at follow-up (mean follow-up 11.3 ± 4.6 months). Patients with venous graft failure [26 (20%)] had significantly smaller DS (P = 0.013), shorter stenosis length (P = 0.01), and lower extent index (P = 0.015), Sullivan score (P = 0.013), Gensini score (P = 0.04) as compared with those without venous graft failure. Patients with arterial graft failure [13 (11%)] had significantly lower DS (P = 0.008), shorter stenosis length (P = 0.001), and lower extent index (P = 0.03) and Sullivan score (P = 0.023) as compared with those without arterial graft failure. Venous and arterial graft failure are associated with less severe stenosis and less extensive atherosclerosis of the grafted vessel.


Agarose gel as biomaterial or scaffold for implantation surgery: characterization, histological and histomorphometric study on soft tissue response.
Maxillofacial, orthopedic, oral, and plastic surgery require materials for tissue augmentation, guided regeneration, and tissue engineering approaches. In this study, the aim was to develop and characterize a new extrudable hydrogel, based on agarose gel (AG; 1.5% wt) and to evaluate the local effects after subcutaneous implantation in comparison with collagen and hyaluronic acid. AG chemical-physical properties were ascertained through Fourier transform infrared (FT-IR) spectroscopy and rheological analysis. In vivo subcutaneous implants were performed, and histological and histomorphometric evaluations were done at 1, 4, 12, and 16 weeks. FT-IR confirmed that spectroscopic properties were the same for the baseline agarose and rheological characterization established that AG is a weak hydrogel. Subcutaneous AG implants induced new vessels and fibrous tissue formation rich in neutrophils; the capsule thickness around AG increased until the 12th week but remained thinner than those around hyaluronic acid and collagen. At 16 weeks, the thickness of the capsule significantly decreased around all materials. This study confirmed that 1.5% wt AG possesses some of the most important features of the ideal biocompatible material: safety, effectiveness, costless, and easily obtained with specific chemical and geometrical characters; the AG can represent a finely controllable and biodegradable polymeric system for cells and drug delivery applications.


A pan-cancer analysis of anti-proliferative protein family genes for therapeutic targets in cancer.
The recently discovered APRO (anti-proliferative protein) family encodes a group of trans-membrane glycoproteins and includes 6 members: TOB1, TOB2, BTG1, BTG2, BTG3 and BTG4. The APRO family is reportedly associated with the initiation and progression of cancers. This study aims to undertake a comprehensive investigation of the APRO family of proteins as a prognostic biomarker in various human tumors. We performed a pan-cancer analysis of the APRO family based on The Cancer Genome Atlas (TCGA). With the bioinformatics methods, we explored the prognostic value of the APRO family and the correlation between APRO family expression and tumor mutation burden (TMB), microsatellite instability (MSI), drug sensitivity, and immunotherapy in numerous cancers. Our results show that the APRO family was primarily down-regulated in cancer samples. The expression of APRO family members was linked with patient prognosis. In addition, APRO family genes showed significant association with immune infiltrate subtypes, tumor microenvironment, and tumor cell stemness. Finally, our study also demonstrated the relationship between APRO family genes and drug sensitivity. This study provides comprehensive information to understand the APRO family's role as an oncogene and predictor of survival in some tumor types.


Access to Higher Education and Adolescent Fertility in Chile.
This study investigates gender differences in the association between adolescent fertility and the likelihood of initiating higher education among young Chilean men and women. We adopt an entropy balancing strategy to estimate the association between adolescent fertility and the likelihood of starting higher education while accounting for potential selection into early childbearing due to socioeconomic status and prior academic achievement. We use data from official national registers that cover a cohort of Chilean students who attended publicly funded schools and who successfully completed secondary schooling between 2011 and 2022. Our results indicate that adolescent mothers are 15 percentage points less likely to initiate higher education than their peers who did not give birth during adolescence. In comparison, teenage fathers are 20 percentage points less likely to do so than their childless counterparts. Our findings stand in contrast to previously identified disadvantage patterns for secondary school completion, whereby adolescent fertility more significantly hinders schooling completion for women relative to men. We contend that this reversal may be related to traditional gender-role expectations in Chile, which encourage young fathers to act as providers and, therefore, may be prevented from continuing on their education path into tertiary studies.


Arsenic trioxide induces autophagy and apoptosis in human glioma cells in vitro and in vivo through downregulation of survivin.
Gliomas are the most aggressive of all human malignancies. Survivin is overexpressed in gliomas, and overexpression of survivin is associated with the progression of gliomas and the poor prognosis of glioma patients. Arsenic trioxide (ATO) is used in patients with acute promyelocytic leukemia and is active in vitro in several solid tumor cell lines. In the present study, the human glioma cell line U118-MG was used to investigate the anti-cancer effect of ATO in vitro and in vivo. The molecular mechanisms of the relationship between cell death (autophagy and apoptosis) and survivin were analyzed. ATO reduced cell viability through an increase in mitotic cells in a concentration-dependent manner. The mechanisms of ATO-induced autophagy and apoptosis were mediated by the inhibition of PI3K/Akt and the activation of MAPK signaling pathways. The ATO treatment of U118-MG cells pre-treated with specific chemical inhibitors of PI3K/AKT and MAPK significantly changed the cytotoxicity and the expression of survivin, suggesting that survivin plays a pivotal role in ATO-induced cell death. When U118-MG cells were transfected with survivin shRNA, the results demonstrated a significant increase in apoptotic and autophagic cells. In in vivo studies, the ATO treatment of SCID mice showed a significant tumor growth delay time and the decreased expression of survivin in tumor tissue. An important result from the current study is the finding that survivin could suppress both autophagy and apoptosis in glioma cells. This study suggests that ATO treatment or survivin inhibition could be a novel therapeutic strategy in malignant gliomas.


Mercury operon regulation by the merR gene of the organomercurial resistance system of plasmid pDU1358.
The structural basis for induction of the mercury resistance operon with inorganic mercury and with the organomercurial compound phenylmercuric acetate was addressed by DNA sequencing analysis and by lac fusion transcription experiments regulated by merR in trans from broad-spectrum-resistance plasmid pDU1358 (Hg2+ and phenylmercury responding). The lac fusion results were compared with those from a narrow-spectrum-resistance (Hg2+ responding but not phenylmercuric responding) operon and the pDU1358 merR deleted at the 3' end. The nucleotide sequence of the beginning region of the broad-spectrum mer operon of plasmid pDU1358 was determined, including that of the merR gene, the operator-promoter region, the merT and merP genes, and the first 60% of the merA gene. Comparison of this sequence with DNA sequences of narrow-spectrum mer operons from transposon Tn501 and plasmid R100 showed that a major difference occurred in the 3' 29 base pairs of the merR gene, resulting in unrelated C-terminal 10 amino acids. A hybrid mer operon consisting of the merR gene from pDU1358, a hybrid merA gene (determining mercuric reductase enzyme), and lacking the merB gene (determining phenylmercury lyase activity) was inducible by both phenylmercury and inorganic Hg2+. This shows that organomercurial lyase is not needed for induction by organomercurial compounds. A mutant form of pDU1358 merR missing the C-terminal 17 amino acids responded to inorganic Hg2+ but not to phenylmercury. Thus, the C-terminal region of the MerR protein of the pDU1358 mer operon is involved in the recognition of phenylmercury.


Cigarettes, genetic background, and menopausal timing: the presence of single nucleotide polymorphisms in cytochrome P450 genes is associated with increased risk of natural menopause in European-American smokers.
This study aims to evaluate associations between variations in genes involved in the metabolism of environmental chemicals and steroid hormones and risk of menopause in smokers. Survival analysis was performed on 410 eligible participants from the Penn Ovarian Aging study (ongoing for 14 years), a cohort study of late-reproductive-age women. Single nucleotide polymorphisms at the following loci were studied: COMT Val158Met, CYP1B1*4 Asn452Ser, CYP1B1*3 Leu432Val, and CYP3A4*1B. Significant interactions between smoking and single nucleotide polymorphisms were observed in European-American carriers of CYP3A4*1B and CYP1B1*3, supporting a greater risk of menopause entry compared with those not carrying these alleles. Among CYP1B1*3 carriers, smokers had a greater risk of menopause entry than nonsmokers (adjusted hazard ratio [HR], 2.26; 95% CI, 1.4-3.67; median time to menopause, 10.42 and 11.07 y, respectively). No association between smoking and menopause was identified in CYP1B1 wild types. Among CYP3A4*1B carriers, smokers were at greater risk for menopause entry than nonsmokers (adjusted HR, 15.1; 95% CI, 3.31-69.2; median time to menopause, 11.36 and 13.91 y, respectively). Risk of menopause entry in CYP3A4 wild types who smoked was far lower (adjusted HR, 1.59; 95% CI, 1.03-2.44). Heavily smoking CYP1B1*3 carriers (adjusted HR, 3.0; 95% CI, 1.54-5.84; median time to menopause, 10.41 y) and heavily smoking CYP3A4*1B carriers (adjusted HR, 17.79; 95% CI, 3.21-98.65; median time to menopause, 5.09 y) had the greatest risk of menopause entry. Our finding that the risk of menopause entry in European-American smokers varies depending on genetic background represents a novel gene-environment interaction in reproductive aging.


The clean plate club: about 92% of self-served food is eaten.
Many eating studies in psychology, consumer behavior and marketing journals are dismissed, because they focus on how much one serves and not how much is eaten. We develop a means of estimating the percentage of self-served food that is consumed under various conditions. An aggregate analysis was conducted of studies where participants served themselves food and where actual intake was measured. Analyses explored what percentage of food was consumed depending on population, food and situational cues and generally showed that adults consistently consume the vast majority (91.7%) of what they serve themselves. This was higher for meals (92.8%) than for snacks (76.1%) and higher when a person was not distracted (97.1%) than when he or she was distracted (88.8%). The percentage eaten did not vary between lab (90.7%) and field settings (91.9%). Because many eating behavior studies outside of nutrition measure food selection, but not intake, the aggregate estimates presented in this research can enable obesity, nutrition and public health researchers to extrapolate how much may have been eaten in such studies. Doing so will extend their relevance to better understanding eating behavior and better developing solutions to overeating.


SLC45A3-ELK4 chimera in prostate cancer: spotlight on cis-splicing.
Using a series of detailed experiments, Zhang and colleagues establish that the prostate cancer RNA chimera SLC45A3-ELK4 is generated by cis-splicing between the 2 adjacent genes and does not involve DNA rearrangements or trans-splicing. The chimera expression is induced by androgen treatment likely by overcoming the read-through block imposed by the intergenic CCCTC insulators bound by CCCTC-binding factor repressor protein. The chimeric transcript, but not wild-type ELK4, is shown to augment prostate cancer cell proliferation.


A protocol for species delineation of public DNA databases, applied to the Insecta.
Public DNA databases are composed of data from many different taxa, although the taxonomic annotation on sequences is not always complete, which impedes the utilization of mined data for species-level applications. There is much ongoing work on species identification and delineation based on the molecular data itself, although applying species clustering to whole databases requires consolidation of results from numerous undefined gene regions, and introduces significant obstacles in data organization and computational load. In the current paper, we demonstrate an approach for species delineation of a sequence database. All DNA sequences for the insects were obtained and processed. After filtration of duplicated data, delineation of the database into species or molecular operational taxonomic units (MOTUs) followed a three-step process in which (i) the genetic loci L are partitioned, (ii) the species S are delineated within each locus, then (iii) species units are matched across loci to form the matrix L × S, a set of global (multilocus) species units. Partitioning the database into a set of homologous gene fragments was achieved by Markov clustering using edge weights calculated from the amount of overlap between pairs of sequences, then delineation of species units and assignment of species names were performed for the set of genes necessary to capture most of the species diversity. The complexity of computing pairwise similarities for species clustering was substantial at the cytochrome oxidase subunit I locus in particular, but made feasible through the development of software that performs pairwise alignments within the taxonomic framework, while accounting for the different ranks at which sequences are labeled with taxonomic information. Over 24 different homologs, the unidentified sequences numbered approximately 194,000, containing 41,525 species IDs (98.7% of all found in the insect database), and were grouped into 59,173 single-locus MOTUs by hierarchical clustering under parameters optimized independently for each locus. Species units from different loci were matched using a multipartite matching algorithm to form multilocus species units with minimal incongruence between loci. After matching, the insect database as represented by these 24 loci was found to be composed of 78,091 species units in total. 38,574 of these units contained only species labeled data, 34,891 contained only unlabeled data, leaving 4,626 units composed both of labeled and unlabeled sequences. In addition to giving estimates of species diversity of sequence repositories, the protocol developed here will facilitate species-level applications of modern-day sequence data sets. In particular, the L × S matrix represents a post-taxonomic framework that can be used for species-level organization of metagenomic data, and incorporation of these methods into phylogenetic pipelines will yield matrices more representative of species diversity.


Human Mpox in People Living with HIV: Epidemiologic and Clinical Perspectives from Nigeria.
Sub-Saharan Africa (SSA) is disproportionately affected by mpox and HIV. We described epidemiologic trends and clinical experiences in the management of mpox in people living with HIV (PLWH) in Nigeria and further examined how the rapidly accumulating body of knowledge from the 2022 global mpox outbreak might be explored to improve mpox care in PLWH in SSA. During the 2017/2018 Nigerian mpox outbreak, we reported that 9/40 (22.5%) hospitalized mpox patients with known HIV status were PLWH. In the 2022 global mpox outbreak, 52% of confirmed mpox cases with known HIV status were PLWH, predominantly sexual and gender minority groups. However, substantial missing data on HIV status of confirmed mpox cases highlights a critical gap in HIV testing as a component of mpox management. Before 2022, sexual activity was not commonly linked to mpox transmission, but this was identified as a major driver of transmission during the 2022 mpox outbreak. Notable sexual history observed in Nigerian mpox patients in 2017/2018 suggests that the contribution of sexual activity in human-to-human mpox transmission might have been underappreciated for years. Our cohort of PLWH with mpox, predominantly individuals with advanced or uncontrolled HIV, were significantly more likely to experience severe mpox manifestations and prolonged disease compared with those without HIV. This contrasts with the generally less remarkable differences in mpox presentation between people with and without HIV in Western countries, an observation that can be at least partially explained by more stable HIV disease. The unavailability of mpox antiviral drugs and vaccines in SSA highlights global inequity in mpox response, which requires an urgent attention. As mpox countermeasures become available in SSA, lessons learned from their use in Western countries could provide important guidance for care providers in SSA. Public health measures to mitigate stigmatization in PLWH with mpox is also critical.


Coach Competences to Induce Positive Affective Reactions in Sport and Exercise-A Qualitative Study.
Positive affective reactions are a crucial aspect in physical activity maintenance. Affective reactions to sport and exercise were found to be important factors of physical activity. Coaches could be an important medium to induce positive affective reactions of participants in sport and exercise. Understanding how coaches trigger positive affective reactions (AR) during physical activity is a crucial aspect for increasing maintenance in sport and exercise. The aim of this study is to identify the competences of the coaches which are associated with perceived positive AR of participants during sport and exercise. To identify these factors, semistructured in-depth interviews were conducted with 18 participants, who take part in sport and exercise (nine female and nine male) of heterogeneous age (mean age 42.6; SD = 19.25; under 30 years, 30 to 60 years, 60 years and above) and who have different athletic backgrounds (individual sports, team sports, and gym classes). Four key coach competence factors were identified and used to design an integrated model. Three general competences: context sensitivity, social⁻emotional competences, professional competences, and the specific competences in the behaviour-related competences.


One-pot multi-tracer synthesis of novel (18)F-labeled PET imaging agents.
(18)F labeled phosphonium salts are increasingly important molecular probes for targeting the mitochondrial membrane potential depletion during apoptosis and for detecting myocardial perfusion deficit. Here, we introduce three new tracers, [(18)F]MitoPhos_04, [(18)F]MitoPhos_05, and [(18)F]MitoPhos_07, that have the potential to act as mitochondrial imaging agents. Moreover, they have the added advantage of being synthesized in the same reaction vial from one radiolabeled synthon, demonstrating a new approach to synthesizing multiple tracers in one-pot, which is a highly useful means for increasing the throughput of radiotracer development. The radiosynthesis of the tracers was carried out on a fully automated system via a facile two-step reaction. Utilizing the radiolabeling of an ethyl azide, a copper-mediated 1,3-cycloaddition reaction and isolation via semiprep high-performance liquid chromatography (HPLC) allowed for the simultaneous synthesis of two or three tracers with a total synthesis time of less than 1 h.


Comparison of bolus remifentanil versus bolus fentanyl for blunting cardiovascular intubation responses in children: a randomized, double-blind study.
The authors found no study to compare the efficacy of bolus dose fentanyl and remifentanil blunting the cardiovascular intubation response in children, so they designed this randomized, double-blind clinical study to assess the effects of remifentanil 2 microg/kg and fentanyl 2 microg/kg by bolus injection on the cardiovascular intubation response in healthy children. One hundred and two children, the American Society of Anesthesiologists (ASA) physical status 1-2 and scheduled for elective plastic surgery under general anesthesia, were randomly divided into one of two groups to receive the following treatments in a double blind manner: remifentanil 2 microg/kg (Group R) and fentanyl 2 microg/kg (Group F) when anesthesia was induced with propofol and vecuronium. The orotracheal intubation was performed using a direct laryngoscope. Blood pressure (BP) and heart rate (HR) were recorded before anesthesia induction (baseline values), immediately before intubation, at intubation and every minute for 5 minutes after intubation. The percent changes of systolic blood pressure (SBP) and HR relative to baseline values and the rate pressure product (RPP) at every observing point were calculated. The incidences of SBP and HR percent changes >30% of baseline values and RPP >22,000 during the observation were recorded. There were no significant differences between groups in the demographic data, baseline values of BP and HR and the intubation time. As compared to baseline values, BP, HR and RPP at intubation and their maximum values during observation increased significantly in Group F, but they all decreased significantly in Group R. BP, HR and RPP at all observed points, and their maximum values during the observation, were significantly different between groups. There were also significant differences between groups in the percent change of SBP and HR relative to baseline values at all observed points and their maximum percent changes during the observation. The incidences of SBP and HR percent increased >30% of the baseline values and RPP >22,000 during the observation, were significantly higher in Group F than in Group R, but the incidences of SBP and HR percent decreased >30% of baseline values were significantly lower in Group F compared with Group R. When used as part of routine anesthesia induction with propofol and vecuronium in children, fentanyl 2 microg/kg by bolus injection fails to effectively depress the cardiovascular intubation response. Remifentanil 2 microg/kg by bolus injection can completely abolish the cardiovascular intubation response, but also cause more adverse complications of temporary significant cardiovascular depression.


Adsorption and desorption of crystal violet and basic red 9 by multi-walled carbon nanotubes.
Batch adsorption and desorption of crystal violet (CV) and basic red 9 (BR9) on multi-walled carbon nanotubes (MWCNTs) were conducted. To investigate the possible mechanisms of adsorption/desorption hysteresis, oxidized MWCNTs (O-MWCNTs) with more oxygen-containing groups were obtained by oxidizing as-purchased MWCNTs (A-MWCNTs) using nitric acid. The adsorption kinetics could be described by the pseudo-second-order model, suggesting that chemical reactions are the rate-limiting steps. The adsorption isotherms were fitted well by the Langmuir model, which suggests that, in addition to π-π interactions, chemical reactions significantly affect the adsorption. The adsorption capacity decreased in the order of CV on A-MWCNTs, BR9 on A-MWCNTs, and BR9 on O-MWCNTs, possibly because the amidation between BR9 and the surface groups of MWCNTs results in steric hindrance, which limits the adsorption of BR9 to inner grooves between CNT bundles. Adsorption/desorption hysteresis was observed for BR9 but not for CV. It was found that the π-π interaction and molecular entrapment were not responsible for the adsorption/desorption hysteresis. The hysteresis might be caused by the irreversible amide bonds between BR9 and MWCNTs. The results indicate that the steric hindrance due to the three-dimensional structure of organic compounds plays an important role in both adsorption/desorption kinetics and equilibria.