Mean platelet volume is increased in hyperthyroidism.
In 28 unselected patients with hyperthyroidism, platelet count, platelet hematocrit, mean platelet volume, and platelet distribution width were measured at the time of presentation and again when the patients were euthyroid. On return to the euthyroid state, there were highly significant falls in the mean values of the mean platelet volume (16% decline, P less than 0.001) and the platelet hematocrit (16% decline, P less than 0.001) and a slight but highly significant increase in the mean value of the platelet distribution width (2% increase, P less than 0.01). A decline in mean platelet volume was observed in 24 of 28 patients (86%); three patients showed no change. There was no significant change in the mean value of the platelet count. The observed effects of thyrotoxicosis on platelets appeared to be largely independent of the well-known effects on erythrocytes and white blood cells. An increase in mean platelet volume is a regular feature of hyperthyroidism that has not previously been described.


Predictors of Outcome After Primary Total Joint Replacement.
Total hip and knee replacements are frequently performed curative treatment options in end-stage arthritis. In this study, we analyzed clinical outcome, complications, and predictors of outcome in modern joint replacement. In a retrospective analysis of over 2000 primary total hip and knee replacements from our institutional joint registry, responder rates for positive outcome as defined by the OMERACT-OARSI criteria, postoperative complication rates, and patient-reported outcome measures (EQ-5D, WOMAC) within the first year were compared between hip and knee replacements. Furthermore, preoperative risk factors associated with nonresponder rate were evaluated. Positive responder rate was higher for hip replacements with 92.8% (1145/1234) than for knee replacements with 86.1% (839/975, P < .001). Infection rates were lower (P = .04), whereas intraoperative fracture occurred more frequently (P = .001) in hip than in knee replacements. Patient-reported outcome measures 1 year after surgery were higher in hip than in knee replacements with EQ-5D (0.88 ± 0.17 to 0.81 ± 0.19, P < .001) and WOMAC (84.58 ± 16.73 to 74.31 ± 18.94, P < .001). Besides the type of joint replacement (hazard ratio [HR] 2.0, P < .001), high preoperative outcome measures (HR 7.4, P < .001) and male gender (HR 1.4, P = .05) were independent risk factors of nonresponders after joint replacement. Both total hip and knee replacements are safe procedures with low complication rates. Still, postoperative outcome is higher in hip than in knee arthroplasty. High preoperative clinical scores are a risk factor for poor clinical improvement following total joint replacement and can be used in counseling patients in the office.


Critical intracellular Ca2+ concentration for all-or-none Ca2+ spiking in single smooth muscle cells.
Neurotransmitters induce contractions of smooth muscle cells initially by mobilizing Ca2+ from intracellular Ca2+ stores through inositol 1,4,5-trisphosphate (InsP3) receptors. Here we studied roles of the molecules involved in Ca2+ mobilization in single smooth muscle cells. A slow rise in cytoplasmic Ca2+ ([Ca2+]i) in agonist-stimulated smooth muscle cells was followed by a wave of rapid regenerative Ca2+ release as the local [Ca2+]i reached a critical concentration of approximately 160 nM. Neither feedback regulation of phospholipase C nor caffeine-sensitive Ca(2+)-induced Ca2+ release was found to be required in the regenerative Ca2+ release. These results indicate that Ca(2+)-dependent feedback control of InsP3-induced Ca2+ release plays a dominant role in the generation of the regenerative Ca2+ release. The resulting Ca2+ release in a whole cell was an all-or-none event, i.e. constant peak [Ca2+]i was attained with agonist concentrations above the threshold value. This finding suggests a possible digital mode involved in the neural control of smooth muscle contraction.


Spatial Dynamics and Spread of Ecosystem Engineers: Two Patch Analysis.
Ecosystem engineers are organisms characterized by interacting with other organisms thorough physical modifications or modifying their habitat. Examples of ecosystem engineers include Spartina alterniflora cordgrass or the zebra mussel Dreissena polymorpha. For both of these, the effect of modifying the environment can be nonlocal, affecting other regions farther away from the region populated by the ecosystem engineer. This shows the importance of understanding the population dynamics of ecosystem engineers in a spatial context. To do this, we have developed an extension of the ecosystem engineer population model of Cuddington et al. (Am Natur, 2009. https://doi.org/10.1086/597216 ) to the simplest spatial model, incorporating two local populations. We use this model to understand the relationship between dispersal and engineering effects, both at local and regional scales. Our main result is that the delayed Allee effect induced in the nonspatial model is extended to the spatial model, so the spread dynamics of an ecosystem engineer can be similar to the Allee case. However, there are more complex possibilities due to the two components of the dynamics. We also find quantitative guidelines that explain the interaction between spread of the environment modification and organism spread.


Expression profiling and antibacterial analysis of cd36 in mandarin fish, Siniperca chuatsi.
Cd36 is classified as a class B scavenger receptor and has also been identified as a pattern recognition receptor. In this study, we investigated the genomic structure and molecular characteristics of cd36 in mandarin fish (Siniperca chuatsi), examined its tissue distribution, and evaluated its antibacterial activity. Genomic structure analysis showed that Sccd36 consists of 12 exons and 11 introns. Sequencing analysis confirmed that the open reading frame of Sccd36 contains 1410 bp, encoding 469 amino acids. Sccd36 is deeply conserved with other vertebrates in terms of genomic structure, gene loci and molecular evolution, and the feature of two transmembrane was observed in ScCd36 through structural prediction. Sccd36 was constitutively expressed in all tissues tested, with the strongest expression in the intestine, followed by the heart and the kidney. Dramatic changes of Sccd36 mRNA were detected in mucosal tissues, including the intestine, gill and skin, when stimulated by the microbial ligands lipopolysaccharide and lipoteichoic acid. In addition, ScCd36 was identified as having strong binding ability to microbial ligands and antibacterial activity against the gram-negative bacteria Aeromonas hydrophila and the gram-positive bacteria Streptococcus lactis. Furthermore, we verified that the genetic ablation of cd36 impaired the resistance of fish to bacterial challenge by using zebrafish cd36 knockout line. In conclusion, our findings suggest that ScCd36 plays a crucial role in the innate immune response of mandarin fish against bacterial infections. This also sets the stage for further exploration into the antibacterial function of Cd36 in lower vertebrate species.


Economic consequences of routine coronary angiography in low- and intermediate-risk patients with unstable angina pectoris.
In low- and intermediate-risk patients with unstable angina pectoris (UAP) and non-ST-elevation acute myocardial infarction (NSTEAMI), routine early invasive management with coronary angiography does not decrease the risk of death or AMI. The economic consequences of this strategy in low- and intermediate-risk patients are unknown. We applied a risk prediction rule to a multihospital practice database and to the population of the Thrombolysis In Myocardial Ischemia trial, phase IIIB (TIMI 3B), which compared early invasive with conservative therapy for UAP and NSTEAMI. We then analyzed the effect of an early invasive strategy with regard to the composite end point of death, AMI, or rehospitalization for ischemia at rest. A logistic regression model was used to compare outcomes in patients with high versus low or intermediate risk scores. The costs and benefits of early invasive management in low- or intermediate-risk patients were assessed. In the practice database, 56% of patients with UAP and NSTEAMI who had low or intermediate risk scores underwent early cardiac catheterization, although early invasive management of these lower risk patients has not been associated with a reduction in the rate of death or MI. In TIMI 3B, when rehospitalization for ischemia at rest was added to the composite end point, invasive management was superior to conservative management at 42 days (p = 0.005) and at 1 year (p = 0.03). If all low- or intermediate-risk patients randomized to conservative therapy in that trial had been treated instead with an early invasive strategy, an estimated 5.4% of rehospitalizations would have been avoided. Within TIMI 3B, such a routine invasive strategy would have resulted in an additional cost of 2,695,700 US dollars with no effect on death or AMI, but it would have led to 34 fewer rehospitalizations. This expenditure of 79,285 US dollars per hospitalization prevented far exceeds the monetary cost of rehospitalization (14,000 US dollars). Although common in clinical practice, routine early invasive management of low- or intermediate-risk patients with UAP generates substantial health-care costs without a mortality benefit or decrease in the risk of AMI. Unless the incremental benefit in quality of life from prevented rehospitalizations for UAP is judged to be worth the large incremental cost (79,285 US dollars per hospitalization prevented), such a strategy is unlikely to be cost effective.


Methods to assess olfaction in pediatric patients: a systematic review from the international YO-IFOS study group.
Olfaction is an important sense in children, but its measurement is usually disregarded or neglected. There has been increasing interest in olfaction in recent years, and many olfaction assessment tests have been developed to assess pediatric patients. In this systematic review, we identify and compare different olfaction assessment tests used in the pediatric population DATA SOURCES: Pubmed (Medline), the Cochrane Library, EMBASE and Trip Database. The main outcome was review of the tests used to assess olfaction. The secondary outcomes were review of differences between tests regarding sex, age, exercises and odorants. A total of 18 articles fulfilled the established inclusion criteria. Olfaction assessment in children should combine different methods of evaluation, and not rely only on identification tasks. There are still many questions to answer. There is a great need for a specific test for children under 5 years old. Also, there is not a real cutoff value to define hyposmia yet; real cutoff values and values adapted to children's development are keenly needed.


Cellular architecture of Treponema pallidum: novel flagellum, periplasmic cone, and cell envelope as revealed by cryo electron tomography.
High-resolution cryo electron tomography (cryo-ET) was utilized to visualize Treponema pallidum, the causative agent of syphilis, at the molecular level. Three-dimensional (3D) reconstructions from 304 infectious organisms revealed unprecedented cellular structures of this unusual member of the spirochetal family. High-resolution cryo-ET reconstructions provided detailed structures of the cell envelope, which is significantly different from that of Gram-negative bacteria. The 4-nm lipid bilayer of both outer membrane and cytoplasmic membrane resolved in 3D reconstructions, providing an important marker for interpreting membrane-associated structures. Abundant lipoproteins cover the outer leaflet of the cytoplasmic membrane, in contrast to the rare outer membrane proteins visible by scanning probe microscopy. High-resolution cryo-ET images also provided the first observation of T. pallidum chemoreceptor arrays, as well as structural details of the periplasmically located cone-shaped structure at both ends of the bacterium. Furthermore, 3D subvolume averages of periplasmic flagellar motors and flagellar filaments from living organisms revealed the novel flagellar architectures that may facilitate their rotation within the confining periplasmic space. Our findings provide the most detailed structural understanding of periplasmic flagella and the surrounding cell envelope, which enable this enigmatic bacterium to efficiently penetrate tissue and to escape host immune responses.


Obesogenic endocrine disruptors and obesity: myths and truths.
Obesogenic endocrine disruptors, also known as obesogens, are chemicals potentially involved in weight gain by altering lipid homeostasis and promoting adipogenesis and lipid accumulation. They included compounds to which human population is exposed over daily life such as pesticides/herbicides, industrial and household products, plastics, detergents and personal care products. The window of life during which the exposure happens could lead to different effects. A critical window is during utero and/or neonatal period in which the obesogens could cause subtle changes in gene expression and tissue organization or blunt other levels of biological organization leading to increased susceptibility to diseases in the adulthood. Some of the reasons for this increased sensitivity include the lack of the protective mechanisms that are available in adult such as DNA repair mechanisms, a competent immune system, detoxifying enzymes, liver metabolism and the blood/brain barrier still not fully functional in the fetus or newborn. The mechanisms of action of obesogens lay on their ability to increase the number and/or the size of the adipocytes and to alter appetite, satiety and food preferences. The ability of obesogens to increase fat deposition results in an increased capacity for their own retention due to their lipophilic properties; thus prolonging the exposure and increasing the detrimental metabolic consequences.


Comparative analysis of machine learning-based ultrasound radiomics in predicting malignancy of partially cystic thyroid nodules.
To investigate the application of machine learning (ML) model-based thyroid ultrasound radiomics in the evaluation of malignancy in partially cystic thyroid nodules (PCTNs). One hundred and ninety-two patients with 197 nodules PCTNs from January 2020 to December 2020 were retrospectively analyzed. Radiomics features were extracted based on hand-crafted features from the ultrasound images, and machine learning methods were used to build a classification model by radiomics features. The least absolute shrinkage and selection operator regression was applied to select the features of nonzero coefficients from radiomics features. The prediction performance of the established model was mainly evaluated by the area under the curve (AUC) and accuracy, sensitivity, and specificity. Nineteen radiomics features were extracted from the original images for each nodule. Eight ML classifiers were able to differentiate malignancy in PCTNs. The AUC, accuracy, sensitivity, and specificity of k-Nearest Neighbor (KNN) model were 0.909, 82.95%, 83.33%, and 89.90%, respectively, on the test cohort. The comparative result showed statistically equivalent performance for thyroid nodule diagnosis based on image fusion and single image. In addition, the ML-Based ultrasound radiomics system showed a better AUC as compared with ACR TI-RADS model and the ultrasound features model. The novel ultrasonic-based ML model has an important clinical value for predicting malignancy in PCTNs. It can provide clinicians with a preoperative non-invasive primary screening method for PCTN diagnosis to avoid unnecessary medical investment and improve treatment outcomes.


Transgenerational effect of orthoaminoasotoluol in mice.
Transplacental effect of orthoaminoasotoluol (OAAT) on the liver was studied in 3 generations of CBA mice. OAAT was administered to mice intragastrically at the 17, 18 and 19th day of pregnancy. A high incidence of liver tumors was observed in males (73.1% compared with 40.6% in control animals) and 34.3% in females compared to 4.6% in control animals which were the F1 descendants of treated mothers. The females of the F2 generation which were not in direct contact with OAAT developed a statistically higher, compared with the control incidence of liver tumors (24%). The liver tumor incidence in males of the F2 (20.6%) and F3 (17.8%) generations was lower than in the control group (40.5%). The liver tumor incidence in the controls was similar to that observed in F3 females (4.05%).


The Effect of Copper and Zinc Sources on Liver Copper and Zinc Concentrations and Performance of Beef Cows and Suckling Calves.
To determine the influence of the source of gestational and postnatal Cu and Zn supplementation on cow and calf performance, cows (n = 287) were assigned to one of the following two treatments: (1) inorganic (INORG) treatment, in which cows were supplemented with 15 mg of Cu (as CuSO4) and 15 mg of Zn (as ZnSO4) per kg of diet DM, or (2) organic (ORG) treatment, in which cows were supplemented with 15 mg of Cu (as Cu proteinate; Bioplex Cu, Alltech, Inc., Nicholasville, KY, USA) and 15 mg of Zn (as Zn proteinate; Bioplex Zn, Alltech, Inc., Nicholasville, KY, USA) per kg of diet DM. The treatments were initiated prior to breeding and continued throughout gestation until weaning. Liver biopsies were collected for analysis of mineral content. Cow body condition score (BCS), body weight (BW), pregnancy data, calf weaning weight (WW), and antibody response of the calves were recorded. The cows receiving the INORG treatment had a greater BW (p < 0.05) and BCS (p < 0.01) at breeding in Year 2, while the cows on the ORG treatment had a greater (p < 0.05) BW at weaning in Year 2. The cows that received the ORG mineral had improved (p < 0.05) conception rates in Year 1. The calves receiving the ORG treatment had heavier (p < 0.05) 205-day adjusted WWs.


[Morgagni hernia causing cardiac tamponade].
Morgagni hernia is a rare malformation (3% of diaphragmatic hernias). This hernia is usually asymptomatic in children. We report on a case revealed by an unusual complication. Severe cyanosis was due to right-to-left atrial shunt through the foramen ovale assessed by 2D echocardiography. Diagnosis of the Morgagni hernia was made with CT scan. The intrathoracic liver compressed the right chambers of the heart causing tamponade. Cardiac compression was reversed after surgery and replacement of the liver in the abdomen. Six months after the surgery, the infant was symptom-free with normal size right chambers of the heart.


Cardiac transplantation in adults with aortic valve disease with focus on the bicuspid aortic valve.
The frequency of congenitally bicuspid aortic valves in patients having cardiac transplantation (CT) is unknown. We reviewed 243 explanted hearts in patients having CT at Baylor University Medical Center, Dallas from June 1997 through November 2011 to determine the frequency of a bicuspid aortic valve in this population. Of the 243 explanted hearts, 7 (2.9%) were found to have a congenitally bicuspid aortic valve: 3 had severe aortic valve stenosis and before CT had had the aortic valve replaced; the other 4 had normally functioning bicuspid valves and underwent CT for cardiomyopathy (ischemic in 1, idiopathic in 2, and hypertrophic in 1). Review of previously published reports of CT and aortic valve disease disclosed that 4 patients had had aortic valve replacement (AVR) from 2 to 8 years before CT, 3 had AVR or aortic valve repair of the donor heart at the time of CT, and 4 had AVR or transcatheter aortic valve implantation from 1 to 14 years after CT. Some of these aortic valve replacements, before, at the time of, or after CT were in patients with congenitally bicuspid aortic valves. In conclusion, congenitally bicuspid aortic valves were found in 7 of 243 explanted hearts in patients having CT at a single medical center in a 14-year period: 4 had functioned normally and 3 were severely stenotic. Previous reports of patients having AVR or repair before, during, and after CT were reviewed.


"It's a cause I believe in": factors motivating participation and engagement in longitudinal, respiratory-focused research studies.
Key to the success of any prospective cohort study is the effective recruitment and retention of participants, but the specific factors that influence younger adults of the Millennial generation to participate in research are not well-understood. The objective of this qualitative study was to identify factors that motivated participation and engagement in longitudinal research studies focused on respiratory health among a diverse group of young adults. We conducted qualitative, semi-structured interviews with 50 younger adult participants (aged 25-35 years) regarding factors influencing their participation in longitudinal research studies. Thematic analysis was used to develop, organize, and tabulate the frequency of key themes. In exploratory analyses, we examined for patterns in the distribution of key themes across racial, ethnic, or socioeconomic groups. Participants identified several key themes that affected their willingness to participate in longitudinal studies. These included the health-related benefits generated by research (both to the individual and to society at-large), factors related to the institution and study team conducting the research, concerns regarding unethical and/or unrepresentative study design, and barriers to participation in research. Certain factors may be more impactful to underrepresented groups, including concerns regarding data privacy and confidentiality. In this diverse group of younger adults, we identified specific factors that motivated participation and predicted high engagement in longitudinal research studies focused on respiratory health. Implementing and integrating these factors into study protocols may improve recruitment and retention, including among participants who are historically underrepresented in research.


Do pilot free trade zones improve the green total factor productivity? Evidence from a quasi-natural experiment in China.
China's pilot free trade zone (PFTZ) is an important national strategy to achieve high-quality development, so it is necessary to discuss the effect of PFTZ implementation on green total factor productivity (GTFP). Based on the data from 279 cities in China from 2004 to 2018, this study takes the establishment of PFTZ as a quasi-natural experiment and uses the difference-in-differences (DID) method to systematically evaluate the effect of PFTZ on urban GTFP. The empirical results of this paper are shown as follows: Firstly, the construction of PFTZ has a significant effect on urban GTFP, and this effect has increased gradually over time. Secondly, the construction of PFTZ mainly promotes the urban GTFP by increasing the level of science and technology innovation, reducing government intervention and improving the level of human capital. Thirdly, the effect of PFTZ construction on GTFP is more pronounced in regions with earlier waves of PFTZ and in western regions where environmental concerns are higher. In addition, there is a significant positive linkage between the construction of the PFTZ and the Belt and Road Initiative to improve the urban GTFP. The findings of this paper enrich the relevant literature on PFTAs and sustainable development and provide a theoretical basis for further promotion of PFTZ construction.


Photodynamic therapy inhibit Fibroblast Growth Factor-10 induced keratinocyte differentiation and proliferation through ROS in Fibroblast Growth Factor Receptor-2b pathway.
5-aminolevulinic acid-photodynamic therapy (ALA-PDT) is known to be effective in several skin diseases such as acne, actinic keratoses, condyloma acuminata. However, some detailed mechanisms of ALA-PDT to treat these skin diseases still remain elusive. In this study, we aimed to investigate mechanism of ALA-PDT in in-vitro and in-vivo models. For in vitro, we use human keratinocyte cell line (HaCaT) cells. CCK-8 was used to detect cell proliferation activity, immunofluorescence and western blotting method to detect the content of keratin (K)1, K6, K16, protein kinase C (PKC), fibroblast growth factor receptor-2b (FGFR2b) protein, ELISA and RT-PCR to detect expression of interleukin (IL) 1α in the cell supernatant, and detect reactive oxygen species (ROS). For in vivo, we use 20 rabbits to induce hyperkeratosis acne model in their ear. Dermatoscope was used to see follicle hyperkeratosis and skin biopsy to analyze histology and immunohistochemical of PKC, FGFR2b, K1, K6 and K16. Results from this study suggest that ROS stimulated by ALA-PDT lead to inhibition of FGFR2b pathway in PKC downstream to cause reduction of IL1α expression, and eventually, keratinocytes differentiation and proliferation. Our data thus reveal a treatment mechanism of ALA-PDT underlying hyperkeratosis related dermatoses.


Closure of the Common Duct -Endonasobiliary Drainage Tubes vs. T Tube: A Comparative Study.
For the last century T tube drainage of the bile duct has remained standard practice following choledochlithotomy. It vents the biliary tree, provides route for cholangiography and management of residual stones. However, T tubes are associated with significant complications. This retrospective study compared the use of Endonasobiliary drainage tubes and the T tube in 66 patients who underwent open choledocholithotomy for effectiveness and complications. Both groups were statistically comparable. Only 15.15% patients in the Endonasobiliary drainage group, while 45.45% patients in the T tube group developed complications. Severe complications such as biliary peritonitis and intraperitoneal collections were noted only in the T tube group. The Endonasobiliary drainage tube was removed significantly earlier and patients from this group were discharged earlier as compared to those in the T tube. The Endonasobiliary drainage tube is as effective as the T tube in postoperative biliary drainage and allows cholangiograms to be performed. Its use is associated with less complications and it can be removed safely earlier than the T tube. Thus patients have a shorter time with tubes and can be discharged home earlier.


Using network analysis to explore co-occurrence patterns in soil microbial communities.
Exploring large environmental datasets generated by high-throughput DNA sequencing technologies requires new analytical approaches to move beyond the basic inventory descriptions of the composition and diversity of natural microbial communities. In order to investigate potential interactions between microbial taxa, network analysis of significant taxon co-occurrence patterns may help to decipher the structure of complex microbial communities across spatial or temporal gradients. Here, we calculated associations between microbial taxa and applied network analysis approaches to a 16S rRNA gene barcoded pyrosequencing dataset containing >160 000 bacterial and archaeal sequences from 151 soil samples from a broad range of ecosystem types. We described the topology of the resulting network and defined operational taxonomic unit categories based on abundance and occupancy (that is, habitat generalists and habitat specialists). Co-occurrence patterns were readily revealed, including general non-random association, common life history strategies at broad taxonomic levels and unexpected relationships between community members. Overall, we demonstrated the potential of exploring inter-taxa correlations to gain a more integrated understanding of microbial community structure and the ecological rules guiding community assembly.


Early-phase physiological response patterns to psychosexual stimuli: comparison of male and female patterns.
The onset and sequential changes of psychosexual arousal for male and female were compared. During an erotic film presentation, genital hemodynamic and groin skin temperature measures of sexual arousal recorded moderate to large increases for both sexes. A sequential analysis revealed strikingly similar male-female response patterns for both the genital and groin measures of arousal. Thus, the commonly held view that males typically show a greater sexual responsivity to visual erotic stimuli than do females was not supported.


Symmetric increased skeletal muscular uptake of F-18 fluoro-deoxyglucose: A clue for the diagnosis of Graves' disease.
F-18 fluoro-deoxyglucose (FDG) uptake in the thyroid and thymus is well reported in patients with Graves' disease. Incidental skeletal muscle uptake has also been reported in other non-musculoskeletal (benign and malignant) pathologies. We report a patient of Graves' disease showing symmetrical skeletal muscle uptake but no thyroidal or thymus uptake of FDG.


Differentiation of stem cells derived from carious teeth into dopaminergic-like cells.
To investigate whether dental pulp stem cells from carious teeth (DPSCs-CT) can differentiate into functional dopaminergic-like (DAergic) cells and provide an alternative cell source in regenerative medicine. Dental pulp stem cells from healthy (DPSCs) and carious teeth (DPSCs-CT) were isolated from young donors. Both cell lines were expanded in identical culture conditions and subsequently differentiated towards DAergic-like cells using pre-defined dopaminergic cocktails. The dopaminergic efficiencies were evaluated both at gene and protein as well as at secretome levels. The efficiency of DPSCs-CT to differentiate into DAergic-like cells was not equivalent to that of DPSCs. This was further reflected in both gene and protein generation whereby key neuronal markers such as nestin, NURR1 and beta-III-tubulin were expressed significantly lower as compared to differentiated DPSCs (P < 0.05). In addition, expressions of transcriptomes related to neurogenesis revealed downregulation of more than 50% of the genes as compared to differentiated DPSC (P < 0.05). Amongst the notable genes were those from the transcription factors family (FLNA, MEF2C, NEUROG2), signalling pathway family (DLL1, Notch1, TGF-β1), neuro-inducer family (BDNF) and cell communication family (APBB1). DPSCs-CT were able to differentiate into DAergic-like cells but not as efficiently as DPSCs. As such, prior to use in regenerative medicine, stem cells from any source should be thoroughly investigated beyond conventional benchmarks such as that proposed by the International Society for Cellular Therapy (ISCT).


The relationship between club drug use and other drug use: a survey of New York City middle school students.
In order to explore the relationship between use of club drugs (crystal methamphetamine, ecstasy, GHB, ketamine), and use of other drugs, survey data collected from 23,780 middle school students in New York City during 2002-2003 was examined. Results of HGLM analyses (a generalization of HLM to accommodate nonlinear outcomes), controlling for the effect of school, indicate that Black students are less likely than White students to use club drugs depending on the timeframe of use. The use of alcohol and/or marijuana predict club drug use regardless of the timeframe of use, and lifetime cigarette use predicts lifetime club drug use. Recommendations for future research and prevention efforts are discussed.


V3 spinal neurons establish a robust and balanced locomotor rhythm during walking.
A robust and well-organized rhythm is a key feature of many neuronal networks, including those that regulate essential behaviors such as circadian rhythmogenesis, breathing, and locomotion. Here we show that excitatory V3-derived neurons are necessary for a robust and organized locomotor rhythm during walking. When V3-mediated neurotransmission is selectively blocked by the expression of the tetanus toxin light chain subunit (TeNT), the regularity and robustness of the locomotor rhythm is severely perturbed. A similar degeneration in the locomotor rhythm occurs when the excitability of V3-derived neurons is reduced acutely by ligand-induced activation of the allatostatin receptor. The V3-derived neurons additionally function to balance the locomotor output between both halves of the spinal cord, thereby ensuring a symmetrical pattern of locomotor activity during walking. We propose that the V3 neurons establish a regular and balanced motor rhythm by distributing excitatory drive between both halves of the spinal cord.


Improved mortality and haemodynamics with milrinone in cardiogenic shock due to acute decompensated heart failure.
Studies in cardiogenic shock (CS) often have a heterogeneous population of patients, including those with acute myocardial infarction and acute decompensated heart failure (ADHF-CS). The therapeutic profile of milrinone may benefit patients with ADHF-CS. We compared the outcomes and haemodynamic trends in ADHF-CS receiving either milrinone or dobutamine. Patients presenting with ADHF-CS (from 2014 to 2020) treated with a single inodilator (milrinone or dobutamine) were included in this study. Clinical characteristics, outcomes, and haemodynamic parameters were collected. The primary endpoint was 30 day mortality, with censoring at the time of transplant or left ventricular assist device implantation. A total of 573 patients were included, of which 366 (63.9%) received milrinone and 207 (36.1%) received dobutamine. Patients receiving milrinone were younger, had better kidney function, and lower lactate at admission. In addition, patients receiving milrinone received mechanical ventilation or vasopressors less frequently, whereas a pulmonary artery catheter was more frequently used. Milrinone use was associated with a lower adjusted risk of 30 day mortality (hazard ratio = 0.52, 95% confidence interval 0.35-0.77). After propensity-matching, the use of milrinone remained associated with a lower mortality (hazard ratio = 0.51, 95% confidence interval 0.27-0.96). These findings were associated with improved pulmonary artery compliance, stroke volume, and right ventricular stroke work index. The use of milrinone compared with dobutamine in patients with ADHF-CS is associated with lower 30 day mortality and improved haemodynamics. These findings warrant further study in future randomized controlled trials.


Hemojuvelin-hepcidin axis modeled and analyzed using Petri nets.
Systems biology approach to investigate biological phenomena seems to be very promising because it is capable to capture one of the fundamental properties of living organisms, i.e. their inherent complexity. It allows for analysis biological entities as complex systems of interacting objects. The first and necessary step of such an analysis is building a precise model of the studied biological system. This model is expressed in the language of some branch of mathematics, as for example, differential equations. During the last two decades the theory of Petri nets has appeared to be very well suited for building models of biological systems. The structure of these nets reflects the structure of interacting biological molecules and processes. Moreover, on one hand, Petri nets have intuitive graphical representation being very helpful in understanding the structure of the system and on the other hand, there is a lot of mathematical methods and software tools supporting an analysis of the properties of the nets. In this paper a Petri net based model of the hemojuvelin-hepcidin axis involved in the maintenance of the human body iron homeostasis is presented. The analysis based mainly on T-invariants of the model properties has been made and some biological conclusions have been drawn.


Uterus transplantation in the rat: model development, surgical learning and morphological evaluation of healing.
Experimental uterus transplantation is a growing research field with the aim to develop a treatment for women with absolute uterus factor infertility. The potential risks of surgery and immunosuppressive treatment involved in uterus transplantation need to be identified and minimized in appropriate animal models before clinical trials commence. The aim of the present study was to develop and evaluate a model for uterus transplantation in the rat that can be reproduced and used in future studies concerning critical aspects of uterine function after transplantation. Animal study. University Hospital. Uterine tissue sampled at different post-operative time points after non-rejecting uterus transplantation in rats. Adult, virgin female rats of inbred Lewis strain served as donors and recipients of uterine transplants. Two individuals with no previous microsurgical training performed the transplantations and learning curves were recorded. When transplant survival exceeded 70% for both surgeons, 15 animals were transplanted and grafted uteri were evaluated at 1, 7 and 21 days after surgery by assessment of morphology and enumeration of infiltrating neutrophilic granulocytes. Animal survival, graft survival, surgery times, uterine morphology, enumeration of infiltrating neutrophilic granulocytes. Both surgeons gained the necessary microsurgical skills needed to achieve above 70% transplant survival at a similar rate. The signs of post-operative inflammation on day one after transplantation were minor and further reduced at later time points. A reproducible model for uterus transplantation in the rat was developed, which can be used in future studies concerning uterine function after allogenic transplantation.


Effects of Ca channel blockers on Ca transport and Ca ATPase in skeletal and cardiac sarcoplasmic reticulum vesicles.
Several Ca channel blockers--verapamil, nifedipine, nimodipine (Bay e 9736), and nitrendipine (Bay e 5009)--had different effects on Ca transport by sarcoplasmic reticulum vesicles from either skeletal or cardiac muscle. Both nimodipine and nitrendipine (1 X 10(-4) M) stimulated Ca sequestration in the absence of a Ca-precipitating anion by either cardiac or skeletal sarcoplasmic reticulum (SR), with nitrendipine being the more potent stimulator. Nifedipine (1 X 10(-4)M) had no significant effect, whereas at higher concentrations (3 X 10(-3) M) verapamil inhibited the Ca sequestration reaction. Nitrendipine stimulated Ca ATPase and Ca sequestration to a similar extent. Stimulation of Ca sequestration by nitrendipine was dependent on drug/membrane phospholipid mole ratios of between 1:4 and 3:1, as well as absolute drug concentration thus suggesting an interaction of the drug with membrane phospholipids. Nifedipine, nitrendipine, nimodipine, and verapamil (1 X 10(-4)M) had no effect on phosphate-supported Ca uptake by skeletal SR, whereas higher concentrations of verapamil (3 X 10(-3)M) inhibited this reaction by either cardiac or skeletal SR. The results of this study suggest that (a) Ca channel blockers have complex and variable effects on SR membranes, (b) these effects are similar in cardiac and skeletal SR, and (c) the effects are in part mediated through an interaction with membrane phospholipids or hydrophobic portions of the Ca ATPase.


Attitudes to Exercise and Diabetes in Young People with Type 1 Diabetes Mellitus: A Qualitative Analysis.
To investigate young people's attitudes to, and understanding of, physical activity on glycaemic control in Type 1 Diabetes Mellitus. Four focus groups with 11-14 and 15-16 year olds were conducted with twelve young people with Type 1 Diabetes, from within a larger study investigating physical activity and fitness. Qualitative analysis of the focus group data was performed using Interpretative Phenomenological Analysis. Four superordinate themes were identified: Benefits of Exercise, Knowledge and Understanding, Information and Training and "You can do anything". Young people felt that exercising helped them to manage their diabetes and had a beneficial psychological and physical impact on their bodies. They reported a lack of knowledge and understanding about diabetes among school staff and other young people. The overwhelming sense from young people was that although diabetes impacts upon their lives, with preparation, physical activity can take place as normal. Whilst young people had an awareness of the physical and psychological benefits of exercise in managing their diabetes, they experienced difficulties at school. Professional support and discussions with young people, giving tailored strategies for managing Type 1 Diabetes during exercise are needed. Healthcare teams should ensure that the support and educational needs of school staff are met. Providing more opportunities to empower young people to take on the responsibility for their Type 1 Diabetes care is merited. Young people felt diabetes did not stop them from participating in activities; it is simply a part of them that needs managing throughout life.


Nonsteroidal anti-inflammatory drug-induced hepatotoxicity.
Nonsteroidal anti-inflammatory drugs are among the most common drugs associated with drug-induced liver injury, with an estimated incidence of between 3 and 23 per 100,000 patient years. Nimesulide, sulindac, and diclofenac seem to be associated with the highest risk and the only risk factor consistently identified is the concomitant use of other hepatotoxic drugs. Diclofenac-induced liver injury is a paradigm for drug-related hepatotoxicity. Recent studies suggest that genetic factors favoring the formation and accumulation of the reactive acylglucuronide metabolite of diclofenac and an enhanced immune response to the metabolite-protein adducts are associated with increased susceptibility to hepatotoxicity.


The urgency-gating model can explain the effects of early evidence.
In a recent report, Winkel, Keuken, van Maanen, Wagenmakers & Forstmann (Psychonomics Bulletin and Review 21(3): 777-784, 2014) show that during a random-dot motion discrimination task, early differences in motion evidence can influence reaction times (RTs) and error rates in human subjects. They use this as an argument in favor of the drift-diffusion model and against the urgency-gating model. However, their implementation of the urgency-gating model is incomplete, as it lacks the low-pass filter that is necessary to deal with noisy input such as the motion signal used in their experimental task. Furthermore, by focusing analyses solely on comparison of mean RTs they overestimate how long early information influences individual trials. Here, we show that if the urgency-gating model is correctly implemented, including a low-pass filter with a 250 ms time constant, it can successfully reproduce the results of the Winkel et al. experiment.


Evaluation of the Effects of Thermal Comfort Conditions on Cardiovascular Diseases in Amasya City, Turkey.
Studies fall short when it comes to determining the relationship between thermal comfort and cardiovascular diseases. Studies examining the relationship between thermal comfort conditions and human health in Turkey, located in the transition zone of air masses at mid-latitudes, are quite limited. This is the first study conducted in Turkey that deals with thermal comfort conditions and CVDs, which is the leading cause of death. This study aimed to examine the relationship between thermal comfort conditions and CVDs of Amasya, a medium-sized exemplary Turkish city. To determine the thermal comfort conditions in the study area between 2014-2019, the physiologically equivalent temperature (PET) index obtained from the Rayman model, which uses hourly air temperature (ºC), relative humidity (%), wind speed (m/s), and cloud cover (octa) data, was used. The relationship between PET values and CVDs was determined by Pearson correlation analysis and linear regression analysis. The study indicated a negative, high, and moderate correlation between PET values and cardiovascular diseases (p < 0.001). The results show that when PET values increase by 1 ºC, patient admissions will decrease by about 104 to 108 patients (-104.737 to -108.619 units.). These results can be informative and guiding for both the protection of public health and studies on climate change and human health.


Investigation of assimilable organic carbon (AOC) and bacterial regrowth in drinking water distribution system.
This paper investigated the variation of assimilable organic carbon (AOC) concentrations in water from several typical water treatment plants and distribution systems in a northern city of China. It is concluded from this study that: (1) The AOC in most of the product water of the studied water treatment plants and the water from the associated distribution systems could not meet the biostability criteria of 50-100 microg/L. (2) Only 4% of the measured AOC concentrations were less than 100 microg/L. However, about half of the measured AOC values were less than 200 microg/L. (3) Better source water quality resulted in lower AOC concentrations. (4) The variation of AOC concentrations in distribution systems was affected by chlorine oxidation and bacterial activity: the former resulted in an increase of AOC value while the latter led to a reduction in AOC. (5) The variation of AOC concentration followed different patterns in different distribution systems or different seasons due to their respective operational characteristics. (6) Less than 30% of AOC could be removed by a conventional treatment process, whereas 30-60% with a maximum of 50-60% could be removed by granular activated carbon (GAC). (7) The observation via scanning electron microscope (SEM) on distribution pipe tubercle samples demonstrated that the pipe inner wall was not smooth and bacteria multiplied in the crevice as well as in the interior wall of distribution pipes.


Cytometric profiles of bone marrow and spleen lymphoid cells after mercury exposure in mice.
The potential immunotoxic effects of mercury chloride on murine bone marrow (bm) cell subpopulations, including analysis of maturation patterns for B-cells, were evaluated by flow cytometric analysis. CD-1 outbred mice were exposed for 28 days to relatively low doses of 25-100 ppm HgCl2 in drinking water and the mercury-related functional cellular changes were validated in a macrophage phagocytosis assay. Lymphocyte subsets from the bone marrow population were stained with PNA lectin and a panel of monoclonal antibodies against cell surface antigens. The incidence of subset-specific staining was also monitored in spleens and thymuses. A dose-effect correlation was noted for the mercury-related activation of macrophage phagocytosis. Subchronic exposure to mercuric chloride resulted in a transient (7-14 day) decrease of the lymphoid/total bm cell ratio and affected the incidence of splenic T-cell subsets, however, without a clear dose-response correlation. The B-cell population in spleen and maturation patterns of B-cells in bm appeared to be unaffected by the mercury exposure. Overall, cytometric analysis of lymphoid cell subsets in murine bone marrow revealed transient and subset-non-specific cell fluctuations after subchronic exposure to inorganic mercury.


Mucoepidermoid carcinoma of the breast, 3 cases report and literature review.
Mucoepidermoid carcinoma (MEC) is one of the most common malignant tumors in salivary glands, with specific histomorphological and molecular characteristics. MEC occurring in breast is more rare. We reported 3 cases of female breast mass, diagnosed as benign nodules by ultrasound. The first 2 cases were pathological diagnosed as breast MEC, low grade, and the third case as breast MEC, medium grade. After pathological diagnosis, 3 patients have expanded the scope of breast resection and lymph node dissection, with negative margin and no lymph node metastasis. In the follow-up observation, the first case was followed up for 24 months, the second case was followed up for 30 months, and the third case was followed up for 12 months. All patients had a good prognosis without evidence of recurrence and metastasis. Breast MEC is extremely rare and estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 negative breast cancer with a good prognosis, which is different from other highly malignant triple-negative breast cancers. reviewed its clinicopathologic morphological characteristics, immunohistochemical markers and molecular characteristics, prognosis and clinical treatment through literature, in order to understanding its clinicopathology and providing reference for clinical precise treatment.


Recognizing internet addiction: prevalence and relationship to academic achievement in adolescents enrolled in urban and rural Greek high schools.
This study aims: a) to estimate the prevalence of internet addiction among adolescents of urban and rural areas in Greece, b) to examine whether the Internet Addiction Test cut-off point is applicable to them and c) to investigate the phenomenon's association with academic achievement. Participants were 2090 adolescents (mean age 16, 1036 males, 1050 females). Young's (1998) Internet Addiction Test and her Diagnostic Questionnaire were applied. School records' grades were retrieved. A 3.1% prevalence revealed, while boys {F (1, 1642) = 6.207, p < .05}, urban residents {F (1, 1642) = 5.53, p > .05} and academic track high school students {F (1, 1642) = 5.30, p < .05} were at higher risk. An Internet Addiction Test score of 51 points (sample's mean = 27.69, SD = 17.38) was proposed as the optimal cut-off point combining high sensitivity (98%) and specificity (91%). Finally, findings illustrated the syndrome's relation to worse academic achievement {F (1, 1725) = 0.93, p > .05}.


A 2-year retrospective analysis of facial injuries in patients treated at department of oral and maxillofacial surgery, IGGDC, Jammu, India.
The incidence of maxillofacial injuries is on the rise due to motor vehicle accidents and increased incidence of violence in recent times. The aim of this retrospective study was to determine the incidence, etiology, and the pattern of fractures in the maxillofacial region. After obtaining permission from the concerned authorities, a predesigned questionnaire was used to collect the necessary data from the department. A retrospective analysis of 787 patients, who suffered trauma and were managed in the Department of Oral and Maxillofacial Surgery, Indira Gandhi Government Dental College (IGGDC), Jammu over a period of 2 years was carried out. Road traffic accident (RTA) was the common cause of maxillofacial injuries. Men sustained more injuries as compared to women. Injuries were most commonly sustained in the age group of 11-40 years, constituting about 76% of all injuries, mandibular fractures were the most common. RTAs were the commonest cause for the maxillofacial injuries.


The Burden of Dementia Spectrum Disorders and Associated Comorbid and Demographic Features.
Dementia spectrum disorders (DSDs) are a major cause of mortality and disability worldwide. DSDs encompass a large group of medical conditions that all ultimately lead to major functional and cognitive decline and disability. Demographic and comorbid conditions that are associated with DSDs have significant prognostic and preventive implications. In this article, we will discuss the global and regional burden of DSDs and cover key demographic and clinical conditions linked with DSDs. In the absence of disease-modifying treatments, the role of primary prevention has become more prominent. Implementation of preventive measures requires an understanding of predisposing and exacerbating factors.


In situ metathesis reaction combined with liquid-phase microextraction based on the solidification of sedimentary ionic liquids for the determination of pyrethroid insecticides in water samples.
A novel dispersion liquid-liquid microextraction method based on the solidification of sedimentary ionic liquids (SSIL-DLLME), in which an in situ metathesis reaction forms an ionic liquid (IL) extraction phase, was developed to determine four pyrethroid insecticides (i.e., permethrin, cyhalothrin, fenpropathrin, and transfluthrin) in water followed by separation using high-performance liquid chromatography. In the developed method, in situ DLLME was used to enhance the extraction efficiency and yield. After centrifugation, the extraction solvent, tributyldodecylphosphonium hexafluorophosphate ([P44412][PF6]), was easily collected by solidification in the bottom of the tube. The effects of various experimental parameters, the quantity of tributyldodecylphosphonium bromide ([P44412]Br), the molar ratio of [P44412]Br to potassium hexafluorophosphate (KPF6), the ionic strength, the temperature of the sample solution, and the centrifugation time, were optimized using a Plackett-Burman design to identify the significant factors that affected the extraction efficiency. These significant factors were then optimized using a central composite design. Under the optimized conditions, the recoveries of the four pyrethroid insecticides at four spiked levels ranged from 87.1% to 101.7%, with relative standard deviations (RSDs) ranging from 0.1% to 5.5%. At concentration levels between 1 and 500 µg/L, good linearity was obtained, with coefficients of determination greater than 0.9995. The limits of detection (LODs) for the four pyrethroid insecticides were in the range of 0.71-1.54 µg/L. The developed method was then successfully used for the determination of pyrethroid insecticides in environmental samples.


Combined radiotherapy with nivolumab for extracranial metastatic malignant melanoma.
We retrospectively evaluated the tumor regression after radiotherapy in combination with the immune checkpoint inhibitor nivolumab for metastatic melanoma. We evaluated the extracranial metastatic melanoma lesions to which concomitant radiotherapy with nivolumab was administered from June 2015 to February 2017. Tumor volume and maximum diameter were measured at the time of pre-radiotherapy and best response, and the tumor reduction rate was assessed in two ways that our hospital adopts: tumor volume and diameter. Seven lesions in five patients were evaluated. The median time from the start of nivolumab treatment to the start of radiotherapy was 5 months (range 0-22 months). The objective response rate was 85.7% in the evaluation by tumor volume and 42.9% by maximum diameter of the tumor. The objective complete response rate was 28.6% in evaluation by tumor volume and 14.3% by maximum dia. The 1-year tumor control rate was 62.5%. The 1- and 2-year overall survival rate after nivolumab treatment were 75% and 50%, respectively. Two patients who obtained a complete response had presented with vitiligo. The combination of radiotherapy and nivolumab treatment produced favorable responses. Vitiligo may be correlated with a good response to concomitant radiotherapy with nivolumab.


Plasmonic efficiencies of nanoparticles made of metal nitrides (TiN, ZrN) compared with gold.
Metal nitrides have been proposed to replace noble metals in plasmonics for some specific applications. In particular, while titanium nitride (TiN) and zirconium nitride (ZrN) possess localized plasmon resonances very similar to gold in magnitude and wavelength, they benefit from a much higher sustainability to temperature. For this reason, they are foreseen as ideal candidates for applications in nanoplasmonics that require high material temperature under operation, such as heat assisted magnetic recording (HAMR) or thermophotovoltaics. This article presents a detailed investigation of the plasmonic properties of TiN and ZrN nanoparticles in comparison with gold nanoparticles, as a function of the nanoparticle morphology. As a main result, metal nitrides are shown to be poor near-field enhancers compared to gold, no matter the nanoparticle morphology and wavelength. The best efficiencies of metal nitrides as compared to gold in term of near-field enhancement are obtained for small and spherical nanoparticles, and they do not exceed 60%. Nanoparticle enlargements or asymmetries are detrimental. These results mitigate the utility of metal nitrides for high-temperature applications such as HAMR, despite their high temperature sustainability. Nevertheless, at resonance, metal nitrides behave as efficient nanosources of heat and could be relevant for applications in thermoplasmonics, where heat generation is not detrimental but desired.


Measurement of the ultrasonic attenuation coefficient of human blood plasma during clotting in the frequency range of 8 to 22 MHz.
The blood coagulation mechanism consists of a series of concatenated chemical reactions, governed by the coagulation factors present in the blood plasma, after the activation of the clot mechanism. The last reaction corresponds to the fibrinogen conversion into fibrin, followed by the fibrin polymerisation and production of a stable fibrin network. During the clotting process, there is a sol-gel transformation of the medium. The subject of the present paper is the measurement of the ultrasonic attenuation coefficient for human blood plasma during the coagulation process, in the frequency range of 8 to 22 MHz. The clot was obtained after the procedure to measure the prothrombin time (approximately 12 s): mixing 150 microL of reconstituted lyophilised normal plasma with 300 microL of reconstituted lyophilised thromboplastin immersed in a water bath with the temperature controlled at 36.5 degrees C. The attenuation coefficient for pure plasma remained constant within the measurement period of 10 s and at frequencies of 8, 9, 10, 15, 20, 21 and 22 MHz. On the other hand, there is a detectable time-decay of the attenuation coefficient for samples of plasma going through the coagulation process and at frequencies of 8, 9, 10 and 15 MHz. The time-decay becomes less and less detectable as the frequency increases and it becomes completely undetectable at 20, 21 and 22 MHz.


Calcium-induced generation of reactive oxygen species in brain mitochondria is mediated by permeability transition.
Mitochondrial uptake of calcium in excitotoxicity is associated with subsequent increase in reactive oxygen species (ROS) generation and delayed cellular calcium deregulation in ischemic and neurodegenerative insults. The mechanisms linking mitochondrial calcium uptake and ROS production remain unknown but activation of the mitochondrial permeability transition (mPT) may be one such mechanism. In the present study, calcium increased ROS generation in isolated rodent brain and human liver mitochondria undergoing mPT despite an associated loss of membrane potential, NADH and respiration. Unspecific permeabilization of the inner mitochondrial membrane by alamethicin likewise increased ROS independently of calcium, and the ROS increase was further potentiated if NAD(H) was added to the system. Importantly, calcium per se did not induce a ROS increase unless mPT was triggered. Twenty-one cyclosporin A analogs were evaluated for inhibition of calcium-induced ROS and their efficacy clearly paralleled their potency of inhibiting mPT-mediated mitochondrial swelling. We conclude that while intact respiring mitochondria possess powerful antioxidant capability, mPT induces a dysregulated oxidative state with loss of GSH- and NADPH-dependent ROS detoxification. We propose that mPT is a significant cause of pathological ROS generation in excitotoxic cell death.


No abomasal curd formation in pre-ruminant calves after ingestion of a clotting milk replacer.
The aim of this study was to ultrasonographically evaluate curd formation in 29 pre-ruminant calves that were fed a clotting milk replacer. Abomasal curd was absent in 8/29 calves at 2 h after feeding. In these eight calves, abomasal contents were observed as an anechoic image with small echogenic spots (five calves), or as an echogenic image with an unclear outline (three calves), but there was no echogenic image with a clear outline corresponding to curd that was visualised in the other 21 calves. The curd was not observed until 7 h after feeding in the eight calves. Our analysis also indicated that the absence of curd formation in the pre-ruminant calves did not have a significant impact on the appearance, appetite and vigour of pre-ruminant calves or on their blood parameters, including serum triglyceride, blood urea nitrogen and glucose concentrations. The study provided the first evidence that the abomasum of some calves does not form curd despite ingestion of a clotting milk replacer.


The heterogeneous and regressive consequences of COVID-19: Evidence from high quality panel data.
Using new data from the first two waves of the Understanding Society COVID-19 Study collected in April and in May 2020 in the UK, we study the labour market shocks that individuals experienced in the first wave of the pandemic, and the steps they and their households took to cope with those shocks. Understanding Society is based on probability samples and the Covid-19 Study is constructed carefully to support valid population inferences. The Covid-19 Study collected novel data on the mitigation strategies that individuals and households employ. Further, prior observation of respondents in the panel allows us to characterize regressivity with respect to pre-pandemic economic positions. Our key findings are that those with precarious employment, aged under 30 and from minority ethnic groups faced the biggest labour market shocks. Almost 50% of individuals have experienced declines in household earnings of at least 10%, but declines are most severe in the bottom pre-pandemic income quintiles. Methods of mitigation vary substantially across groups: borrowing and transfers from family and friends are most prevalent among those most in need.


Intravenous gamma globulin therapy for thrombocytopenic purpura associated with active varicella infection.
Thrombocypenic purpura was noted in a 3-year-old Japanese girl with an active varicella infection. The administration of intravenous gamma globulin (IVG) drastically improved bleeding manifestations as well as the active varicella infection. We believe that IVG should be the first choice of therapy for thrombocytopenic purpura associated with active infections.


Matrix metalloproteinases are associated with brain atrophy in cognitively unimpaired individuals.
Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have been linked to age-related neurodegeneration and Alzheimer's disease (AD), but their role in normal aging is poorly understood. We used linear mixed models to determine if baseline or rate of yearly change in cerebrospinal fluid (CSF) levels of MMP-2; MMP-3; MMP-10; TIMP-123 (composite of TIMP-1, TIMP-2, and TIMP-3); or TIMP-4 predicted changes in bilateral entorhinal cortex thickness, hippocampal volume, or lateral ventricle volume in cognitively unimpaired individuals. We also assessed effects on the CSF AD biomarkers amyloid-β42 and phosphorylated tau181. Low baseline levels of MMP-3 predicted larger ventricle volumes and more entorhinal cortex thinning. Increased CSF MMP-2 levels over time predicted more entorhinal thinning, hippocampal atrophy, and ventricular expansion, while increased TIMP-123 over time predicted ventricular expansion. No MMP/TIMPs predicted changes in CSF AD biomarkers. Notably, we show for the first time that longitudinal increases in MMP-2 and TIMP-123 levels may predict age-associated brain atrophy. In conclusion, MMPs and TIMPs may play a role in brain atrophy in cognitively unimpaired aging.


Reproductive success, postpartum maternal behavior, and masculine sexual behavior of neonatally androgenized female hamsters.
Sex differences in maternal behavior induced by pup stimulation (sensitization) have been reported for rats and hamsters and may be affected by the presence or absence of perinatal androgen treatment. Postpartum maternal behavior and litter survival in golden hamsters treated with testosterone propionate (TP) as neonates were studied. A high dose of TP (300 micrograms)1 eliminated feminine reproductive capacity when given on Day 2 or 4 postpartum and had no discernible effect on Day 12. Treatment on Days 6, 8, or 10 resulted in treatment day-dependent deficiencies in reproductive success which fell short of sterility in most females. These deficiencies included low birth weight, weight gain, and higher litter losses than controls. However, the maternal behavior of TP dams, as measured by retrieval and crouching, appeared to be normal. The disparity between delivery and successful rearing of normal-weight young may include uterine incompetence, lactation deficiency, and hypercannibalism. Behavioral masculinization was a more sensitive index of neonatal androgen action than any aspect of defeminization, but the two phenomena were dissociated in individuals.


Anatomical Partition-Based Deep Learning: An Automatic Nasopharyngeal MRI Recognition Scheme.
Training deep learning (DL) models to automatically recognize diseases in nasopharyngeal MRI is a challenging task, and optimizing the performance of DL models is difficult. To develop a method of training anatomical partition-based DL model which integrates knowledge of clinical anatomical regions in otorhinolaryngology to automatically recognize diseases in nasopharyngeal MRI. Single-center retrospective study. A total of 2485 patients with nasopharyngeal diseases (age range 14-82 years, female, 779[31.3%]) and 600 people with normal nasopharynx (age range 18-78 years, female, 281[46.8%]) were included. 3.0 T; T2WI fast spin-echo sequence. Full images (512 × 512) of 3085 patients constituted 100% of the dataset, 50% and 25% of which were randomly retained as two new datasets. Two new series of images (seg112 image [112 × 112] and seg224 image [224 × 224]) were automatically generated by a segmentation model. Four pretrained neural networks for nasopharyngeal diseases classification were trained under the nine datasets (full image, seg112 image, and seg224 image, each with 100% dataset, 50% dataset, and 25% dataset). The receiver operating characteristic curve was used to evaluate the performance of the models. Analysis of variance was used to compare the performance of the models built with different datasets. Statistical significance was set at P < 0.05. When the 100% dataset was used for training, the performances of the models trained with the seg112 images (average area under the curve [aAUC] 0.949 ± 0.052), seg224 images (aAUC 0.948 ± 0.053), and full images (aAUC 0.935 ± 0.053) were similar (P = 0.611). When the 25% dataset was used for training, the mean aAUC of the models that were trained with seg112 images (0.823 ± 0.116) and seg224 images (0.765 ± 0.155) was significantly higher than the models that were trained with full images (0.640 ± 0.154). The proposed method can potentially improve the performance of the DL model for automatic recognition of diseases in nasopharyngeal MRI. 4 TECHNICAL EFFICACY STAGE: 1.


Breast Cancer Risk Assessment: Moving Beyond BRCA 1 and 2.
The National Cancer Institute estimates that 12.3% of all women (about 1 in 8) would be diagnosed with breast cancer throughout their lifetime. In 2015, a projected 231,840 new cases are expected in the United States, accompanied by 40,290 deaths. Presently, breast cancer is responsible for 6.8% of all cancer deaths, and roughly 30% of all cancers in women. Since the discovery of the BRCA gene in 1994, efforts have been made to develop effective screening methods for breast cancer detection. Although the BRCA gene certainly opened the door to breast cancer genetics, a wide variety of new genes have recently been linked to breast cancer risk, and the tools to screen for genes beyond just BRCA1 and BRCA2 are available. However, the indications for both screening and prevention of inherited predispositions beyond BRCA1 and BRCA2 are not entirely clear, and as a result, much of the ongoing work is aimed at determining the role of broader genetic screening in women deemed at sufficiently high risk for breast cancer based on family history. On this topic, we provide a brief overview of the genes associated with breast cancer risk as well as the technological platforms available to patients. We conclude by discussing recommendations of expert groups and what they practically mean for patients.


Monitoring trace elements in Antarctic penguin chicks from South Shetland Islands, Antarctica.
The concentration of human activities in the near-shore ecosystems from the northern Antarctic Peninsula area can cause an increasing bioavailability of pollutants for the vulnerable Antarctic biota. Penguin chicks can reflect this potential impact in the rookeries during the breeding season. They also can reflect biomagnification phenomena since they are on the top of the Antarctic food chain. The concentrations of Al, Cr, Mn, Fe, Ni, Cu, Zn, As, Se, Cd and Pb were measured by ICP-MS in samples of liver, kidney, muscle, bone, feather and stomach content of gentoo, chinstrap and Adélie penguin chicks (n=15 individuals) collected opportunistically in the Islands of King George and Deception (South Shetland Islands, Antarctica). The detected levels of some trace elements were not as low as it could be expected in the isolated Antarctic region. Penguin chicks can be useful indicators of trace elements abundance in the study areas. Carcasses of Antarctic penguin chicks were used to evaluate the bioavailability of trace elements in the Islands of King George and Deception.


Calcium, vitamin D, and nutrition in elderly adults.
The nutritional needs for optimizing bone health easily can be met by a diet that is high in fruits and vegetables (five or more servings/day), adequate in protein but moderate in animal protein, and with adequate calcium and vitamin D intakes through the consumption of low fat dairy or calcium-fortified foods. Foods are a preferred source to maintaining calcium balance because there are other essential nutrients that are found in high-calcium foods. For those individuals in whom there is inadequate calcium intake from diet, supplemental calcium can be used. Supplemental or dietary calcium should be spread out throughout the day, with 500 mg or less being consumed at each meal to optimize absorption. In all individuals older than 70 years, vitamin D intakes of at least 600 IU per day (up to 1000 IU/day) are recommended, in addition to the calcium requirement of 1200 mg per day. Vitamin D from foods, supplements, and/or multivitamins can be used to meet the vitamin D requirement. In frail elderly individuals with malabsorption and alcoholics, there may be a need to supplement magnesium. Some elderly individuals with indications of poor nutritional status (low albumin levels) or after hip fracture might benefit from protein supplementation and a multivitamin to ensure adequacy of other nutrients.


Weight loss in the clinical setting: applications for cardiac rehabilitation.
Obese coronary patients could benefit significantly from weight reduction. Unfortunately, weight management is not considered a standard component of cardiac rehabilitation programs. This article reviews the characteristics, approach and outcome data for behavioral weigh loss programs. Strategies for implementing a behavior modification treatment as part of a cardiac rehabilitation program are discussed.


Tests and models of nociception and pain in rodents.
Nociception and pain is a large field of both neuroscience and medical research. Over time, various tests and models were developed in rodents to provide tools for fundamental and translational research on the topic. Tests using thermal, mechanical, and chemical stimuli, measures of hyperalgesia and allodynia, models of inflammatory or neuropathic pain, constitute a toolbox available to researchers. These tests and models allowed rapid progress on the anatomo-molecular basis of physiological and pathological pain, even though they have yet to translate into new analgesic drugs. More recently, a growing effort has been put forth trying to assess pain in rats or mice, rather than nociceptive reflexes, or at studying complex states affected by chronic pain. This aids to further improve the translational value of preclinical research in a field with balanced research efforts between fundamental research, preclinical work, and human studies. This review describes classical tests and models of nociception and pain in rodents. It also presents some recent and ongoing developments in nociceptive tests, recent trends for pain evaluation, and raises the question of the appropriateness between tests, models, and procedures.


Human tissue kallikreins 3 and 5 can act as plasminogen activator releasing active plasmin.
Human tissue kallikreins (KLKs) are a group of serine proteases found in many tissues and biological fluids and are differentially expressed in several specific pathologies. Here, we present evidences of the ability of these enzymes to activate plasminogen. Kallikreins 3 and 5 were able to induce plasmin activity after hydrolyzing plasminogen, and we also verified that plasminogen activation was potentiated in the presence of glycosaminoglycans compared with plasminogen activation by tPA. This finding can shed new light on the plasminogen/plasmin system and its involvement in tumor metastasis, in which kallikreins appear to be upregulated.


Land characteristics and land suitability assessment for Styrax sp. in Humbang Hasundutan Regency, North Sumatra, Indonesia.
Styrax sp. is a valuable latex-producing plant in North Sumatra Province, Indonesia, which requires sustainable land use practices to maintain its production and ecological value. This study aimed to assess the land characteristics and suitability of Styrax sp. in Humbang Hasundutan Regency, North Sumatra Province, to support the development of sustainable land use practices for the cultivation of this plant. The study employed a survey method to collect soil samples and evaluated the land suitability using a matching method and Geographic Information System (GIS) techniques. The results showed that Styrax sp. had moderately suitable land suitability in three villages in Humbang Hasundutan Regency. The limiting factors for land suitability were identified as rooting media, nutrient retention, water availability, and erosion hazard. These findings have important implications for the development of sustainable land use practices for Styrax sp. cultivation in the region, which can contribute to the conservation of this valuable plant species and the maintenance of ecological balance. Overall, this study provides valuable insights into the land characteristics and suitability of Styrax sp. in North Sumatra Province and highlights the importance of sustainable land use practices for the conservation of valuable plant species.


Ten year public health impact of 13-valent pneumococcal conjugate vaccination in infants: A modelling analysis.
Pneumococcal disease is a substantial contributor to illness and death in young children globally. The introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in 2000 had a significant impact in preventing pneumococcal disease in both vaccinated children and unvaccinated individuals (through herd effect). A higher valent PCV13 replaced PCV7 in late 2009. This analysis was undertaken to assess how many cases and deaths have been averted over the last decade since PCV13 introduction. A model estimated the number of infants vaccinated annually with PCV13, as well as the number of cases and deaths of invasive pneumococcal disease, pneumococcal pneumonia, and acute otitis media cases averted. PCV13 vaccination was estimated to have prevented 175.2 million cases of all pneumococcal diseases and 624,904 deaths globally between 2010 and 2019. These results demonstrate the substantial public health impact of PCV13 and highlight the importance of increasing the global reach of PCV programs.


The INVEST trial: a randomised feasibility trial of psychologically informed vestibular rehabilitation versus current gold standard physiotherapy for people with Persistent Postural Perceptual Dizziness.
Persistent postural perceptual dizziness (PPPD) is a common and disabling functional neuro-vestibular disorder. We aimed to determine the feasibility and acceptability of conducting a randomised controlled trial of cognitive-behavioural therapy informed vestibular rehabilitation (INVEST intervention) designed for persistent dizziness. A two-armed parallel groups randomised feasibility study of INVEST vs. a time-matched gold standard vestibular rehabilitation (VRT) control. Participants with PPPD were recruited from a specialist vestibular clinic in London, UK. Participants were individually randomised using a minimisation procedure with allocation concealment. Measures of feasibility and clinical outcome were collected and assessed at 4 months. Forty adults with PPPD were randomised to six sessions of INVEST (n = 20) or gold standard VRT (n = 20). Overall, 59% of patients screened met the inclusion criteria, of which 80% enrolled. Acceptability of INVEST, as assessed against the theoretical framework of acceptability (TFA), was excellent and 80% adhered to all 6 sessions. There were small to moderate treatment effects in favour of INVEST across all measures, including dizziness handicap, negative illness perceptions, symptom focussing, fear avoidance, and distress (standardised mean difference [SMD]g = 0.45; SMDg = 0.77; SMDg = 0.56; SMDg = 0.50, respectively). No intervention-related serious adverse events were reported. The study results give strong support for the feasibility of a full-scale trial. Both arms had high rates of recruitment, retention, and acceptability. There was promising support of the benefits of integrated cognitive-behavioural therapy-based vestibular rehabilitation compared to gold standard vestibular rehabilitation. The study fulfilled all the a-priori criteria to advance to a full-scale efficacy trial. ISRCTN10420559.


Prevention and treatment of symblepharon.
Symblepharon after acute conjunctival injury can be prevented by separating the raw surfaces for one to two weeks, until re-epithelialization takes place. We have used a soft contact lens and a conjunctival ring without a corneal center, or lined the eyelid and palpebral conjunctiva with plastic. This often eliminates the need for mucous membrane grafts. Symblepharon can interfere with intraocular surgery and disrupt cataract incisions unless they are divided and separated at the time of surgery.


[Tracheal compression caused by a paratracheal cyst: a rare cause of fatal airway obstruction].
We report on a previously asymptomatic paratracheal cyst leading to an acute airway obstruction. The possibility of clinical misinterpretation of this rare, congenital malformation is emphasised.


A new treatment strategy for advanced idiopathic interstitial pneumonia: living-donor lobar lung transplantation.
Among patients awaiting cadaveric lung transplantation, patients with idiopathic interstitial pneumonia (IIP) have been demonstrated to have the highest mortality rate. Contraindications to cadaveric lung transplantation include current high-dose systemic corticosteroid therapy because it may increase airway complications and various types of infection. To analyze the effect of living-donor lobar lung transplantation (LDLLT) for patients with advanced IIP including those receiving high-dose systemic corticosteroids. Retrospective analysis. Okayama University Hospital and Okayama Medical Center. We report on the first nine patients (seven female and two male; age range, 13 to 55 years) with advanced IIP receiving LDLLT. All nine patients had a very limited life expectancy, and eight patients were dependent on systemic corticosteroid therapy as high as 50 mg/d of prednisone. LDLLT was performed under cardiopulmonary bypass using two lower lobes donated by two healthy relatives. There were no airway complications in the 18 bronchial anastomoses. There was one early death (11%) due to severe acute rejection. Eight patients (89%) are currently alive with a follow-up period of 10 to 48 months. Their vital capacity reached 2.03 +/- 0.20 L (mean +/- SEM), 71.4% of predicted at 1 year. All 18 donors have returned to their previous lifestyles. Excised lungs were pathologically diagnosed as usual interstitial pneumonia (UIP) in six cases and fibrotic nonspecific interstitial pneumonia (NSIP) in three cases. These early follow-up data support the option of LDLLT in patients with advanced IIP, including UIP and fibrotic NSIP, who would die soon otherwise. Current high-dose systemic corticosteroid therapy is not a contraindication in LDLLT.


Endoscopic papillectomy for an ampullary neuroendocrine tumor.
Ampullary neuroendocrine tumors (NETs) are extremely rare, have a high rate of transmural invasion and lymph node metastasis, and are generally recommended for surgery. In contrast, endoscopic papillectomy (EP) for ampullary NET, a low-grade type within the submucosal layer, is feasible and useful to avoid surgery. However, EP for ampullary NET is controversial, there are no consensus guidelines, and international recommendations are lacking. We present the case of a 60-year-old man with an ampullary NET who was successfully treated with EP via a hexagonal snare. Prior to EP, endoscopic ultrasonography, magnetic resonance cholangiopancreatography, and intraductal ultrasonography in endoscopic retrograde cholangiopancreatography were performed to assess for ductal infiltration of the NET. The specimen revealed a low-grade NET measuring 1.0 × 0.8 × 0.7 cm without venous or lymphatic infiltration, which was negative for horizontal and vertical margins. No recurrence was observed over a 12-month follow-up.


BODIPY-based fluorometric sensor array for the highly sensitive identification of heavy-metal ions.
A BODIPY(4,4-difluoro-4-bora-3a,4a-diaza-s-indacene)-based fluorometric sensor array has been developed for the highly sensitive detection of eight heavy-metal ions at micromolar concentration. The di-2-picolyamine (DPA) derivatives combine high affinities for a variety of heavy-metal ions with the capacity to perturb the fluorescence properties of BODIPY, making them perfectly suitable for the design of fluorometric sensor arrays for heavy-metal ions. 12 cross-reactive BODIPY fluorescent indicators provide facile identification of the heavy-metal ions using a standard chemometric approach (hierarchical clustering analysis); no misclassifications were found over 45 trials. Clear differentiation among heavy-metal ions as a function of concentration was also achieved, even down to 10(-7)M. A semi-quantitative interpolation of the heavy-metal concentration is obtained by comparing the total Euclidean distance of the measurement with a set of known concentrations in the library.


Evaluation of the effect of thrombolytic treatment on infarct size and left ventricular function by enzymatic, scintigraphic, and angiographic methods. The European Cooperative Study Group for Recombinant Tissue Type Plasminogen Activator.
In a double-blind trial of the European Cooperative Study Group, 721 patients with acute myocardial infarction of less than 5 hours' duration were given either 100 mg recombinant tissue-type plasminogen activator (rt-PA) intravenously over 3 hours or an equivalent placebo infusion. In a subset of 312 patients, infarct size was assessed by the cumulative myocardial release of alpha-hydroxybutyrate dehydrogenase (HBDH) during the first 72 hours and by planar thallium scintigraphy (index of hypoperfusion) performed 10 to 22 days after the acute event. Left ventricular ejection fraction (LVEF) was determined by contrast and nuclear angiography. The median values of HBDH during the first 72 hours were 20% lower and the median values of thallium-201 28% smaller in the rt-PA group in comparison with controls. A significant but limited improvement of angiographic LVEF (2 absolute percentage points) was also shown in the patients treated with rt-PA. A moderate but statistically significant linear association between both measurements of infarct size and LVEF was found.


n-Hexyl laurate and fourteen related fatty acid esters: new secretory compounds from the julid millipede, Anaulaciulus sp.
A total of fifteen saturated fatty acid esters were newly identified from the secretions of an unidentified Anaulaciulus sp. (Julida: Julidae). The fatty acid components of the esters were composed of normal chain acids (from C(10) to C(14)) and of branched chain acids (from iso-C(12) to iso-C(15) and anteiso-C(15)). The alcohol moieties were all composed of normal chain alcohols varying from n-butanol to n-octanol. The most abundant component found in the total esters was n-hexyl laurate (64.7%). Novel compounds identified from the millipede secretion extracts include six branched iso- and anteiso-fatty esters, an odd-numbered C(11)-fatty acid ester, a C(13)-fatty acid ester, and a C(7)-alcohol ester, all of which were previously undescribed natural products. In addition, a characteristic mixture of benzoquinones, such as 2-methyl-1,4-benzoquinone, 2-methoxy-3-methyl-1,4-benzoquinone, 2,3-dimethoxy-1,4-benzoquinone, 2-methoxy-6-methyl-1,4-benzoquinone, and 2,3-dimethoxy-5-methyl-1,4-benzoquinone were identified from the secretions, together with trace amounts of 1,4-benzoquinone.


HLA-DRB1 shared epitope-dependent DR-DQ haplotypes are associated with both anti-CCP-positive and -negative rheumatoid arthritis in Chinese Han.
The association between Human Leukocyte Antigen (HLA) class II and rheumatoid arthritis (RA) has been extensively studied, but few reported DR-DQ haplotype. Here we investigated the association of HLA-DRB1, DQA1, DQB1, and DR-DQ haplotypes with RA susceptibility and with anti-CCP antibodies in 281 RA patients and 297 control in Han population. High-resolution genotyping were performed. The HLA-DRB1 shared epitope (SE)-encoding allele *0405 displayed the most significant RA association (P = 1.35×10(-6)). The grouped DRB1 SE alleles showed great association with RA (P = 3.88×10(-13)). The DRB1 DRRAA alleles displayed significant protective effects (P = 0.021). The SE-dependent DR-DQ haplotype SE-DQ3/4/5 remained strong association with both anti-CCP -positive (P = 3.71×10(-13)) and -negative RA (P = 3.89×10(-5)). Our study revealed that SE alleles and its haplotypes SE-DQ3/4/5 were highly associated with RA susceptibility in Han population. The SE-DQ3/4/5 haplotypes were associated with both anti-CCP positive RA and -negative RA.


Stability tests in knee ligament injuries.
For 182 knee joints with ligamentous injuries confirmed at surgery the records contained a complete and documented stability examination. In anterior cruciate ligament injuries the Lachman test and the anterior drawer sign were of similar value with regard to the frequency of false negatives - they missed half of the injuries - but their accuracy improved when they were repeated under anesthesia. The pivot shift was useful only under anesthesia. The medial collateral ligament injuries were usually detected because of valgus instability, also without anesthesia. The stability tests done with the patient under anesthesia are sufficiently reliable for making decisions about knee ligament surgery.


The Galleria mellonella Hologenome Supports Microbiota-Independent Metabolism of Long-Chain Hydrocarbon Beeswax.
The greater wax moth, Galleria mellonella, degrades wax and plastic molecules. Despite much interest, the genetic basis of these hallmark traits remains poorly understood. Herein, we assembled high-quality genome and transcriptome data from G. mellonella to investigate long-chain hydrocarbon wax metabolism strategies. Specific carboxylesterase and lipase and fatty-acid-metabolism-related enzymes in the G. mellonella genome are transcriptionally regulated during feeding on beeswax. Strikingly, G. mellonella lacking intestinal microbiota successfully decomposes long-chain fatty acids following wax metabolism, although the intestinal microbiome performs a supplementary role in short-chain fatty acid degradation. Notably, final wax derivatives were detected by gas chromatography even in the absence of gut microbiota. Our findings provide insight into wax moth adaptation and may assist in the development of unique wax-degradation strategies with a similar metabolic approach for a plastic molecule polyethylene biodegradation using organisms without intestinal microbiota.


Semiology of temporal lobe epilepsy in children and adolescents. Value in lateralizing the seizure onset zone [corrected].
To determine the frequency and lateralizing value of clinical seizure symptoms in children and adolescents with drug-resistant temporal lobe epilepsy (TLE). Patients enrolled had to be <18 years of age and seizure free at follow-up for at least 12 months after epilepsy surgery. Patients were assigned to two age groups, children (age<12 years) and adolescents (age>12 and <18 years). Video-tapes were reviewed blinded to patients' demographic data and results of additional investigations by two independent raters. Clinical signs of known lateralizing significance in adults and additional clinical signs without lateralizing value were assessed. 14 patients (eight boys; 2-18 years) fulfilled the inclusion criteria. Inter-observer agreement was excellent (kappa coefficient: 0.82). Compared with adult series, no differences were found concerning overall occurrence of lateralizing signs and lateralizing accuracy. There were age-related differences, however, concerning the occurrence of individual signs: secondary generalization, complex automatisms and version were less frequent in children than in adolescents. Clinical signs of lateralizing value can also be found in children and adolescents, provided that the evaluation protocols used consider developmental aspects.


The Impact of Medicare Low-income Subsidy on Access to Treatment, Treatment Choice, and Oncologic Outcomes in Patients With Metastatic Prostate Cancer.
Patients eligible for Medicare Part D low-income subsidy have lower cost-sharing for both IV and oral cancer therapies. We evaluated associations between low-income subsidy and treatment choice, treatment initiation, and overall survival in patients with metastatic prostate cancer. We identified men aged 66 years and older diagnosed with stage IV prostate cancer between 2010 and 2017 included in the Surveillance, Epidemiology, and End Results-Medicare linked data set. Using linear probability models, we evaluated the impact of low-income subsidy on type of first supplementary treatment (oral vs IV) among patients who received nonandrogen deprivation therapy supplementary systemic therapy, and initiation of any nonandrogen deprivation therapy supplementary systemic therapy. Overall survival was estimated with Kaplan-Meier curves. Of the 5,929 patients included, 1,766 (30%) had low-income subsidy. On multivariable analysis, those with low-income subsidy were more likely to receive oral as opposed to IV treatments compared to patients without low-income subsidy (probability difference: 17%, 95% CI 12, 22). However, patients with low-income subsidy were less likely to initiate any nonandrogen deprivation therapy supplementary systemic therapy (oral or IV) compared to those without low-income subsidy (probability difference: 7.9%, 95% CI 4.8-11). Additionally, patients with low-income subsidy experienced worse overall survival than those without low-income subsidy (P < .001). While low-income subsidy was associated with increased use of more expensive oral therapies in men with metastatic prostate cancer, barriers to accessing these treatments still exist. These findings stress the importance of continued efforts to improve health care access to low-income individuals.


Severe asthma and adherence to peak flow monitoring: longitudinal assessment of psychological aspects.
Adherence in severe asthma is a difficult health problem. Although psychosocial factors may be responsible for non-adherence, few longitudinal studies have investigated their link with adherence, with most studies having focused on pharmacology. Sixty patients with severe asthma were recruited. Adherence was electronically monitored using peak flow measurements at entry and after 1 year of follow-up. Eysenck's Personality Inventory, Rotter's Locus of Control (LOC), and health control beliefs were all studied. Multiple logistic regression (MLR) was used for risk calculations. Initially, subjects with poor adherence had an external LOC (P=.001) and a high extraversion score (P=.003) compared to those with good adherence. The lie score was high in all patients. Nocturnal awakenings were highly significantly correlated with poor adherence (P=.006). After 1 year, patient adherence, extraversion, and neuroticism remained unchanged. The LOC changed in subjects with poor adherence, showing a less "external" orientation (P=.007). The health parameters were better at the end of the study. By MLR analysis, externality, extraversion, and low social desirability were associated with poor adherence. Patients with poor adherence had a greater probability of nocturnal symptoms. No specific personality type was associated with lack of adherence in the present study, but a high extraversion score, a low social desirability score, and a high level of externality were all predictors of poor adherence.


Economic effects of healthy ageing: functional limitation, forgone wages, and medical and long-term care costs.
This study aims to estimate the potential economic benefits of healthy ageing by obtaining estimates of the economic losses generated by functional limitations among middle-aged and older people. Utilising two data sources retrieved from nationally representative samples of the Japanese people, we analysed the association between functional limitation and economic indicators, including labour market outcomes, savings, investment, consumption, and unpaid activities among individuals aged ≥ 60. Using the estimated parameters from our micro-econometric analyses and the official statistics by the Japanese government and a previous study, we calculated the financial costs that can be averted if healthy ageing is achieved as foregone wages and formal medical/long-term care costs incurred by functional limitations. Our micro-econometric analyses found that functional limitation was associated with a 3% point increase in retirement probability, with a stronger association among those aged 60-69. Moreover, functional limitation was linked with higher total health spending and less active involvement in domestic work. Foregone wages generated by functional limitation were estimated to be approximately USD 266.4 million, driven mainly by individuals in their 60s. Long-term care costs, rather than medical care costs, for older people aged ≥ 85 accounted for most of the additional costs, indicating that the estimated medical and long-term costs generated by functional limitations were approximately USD 72.7 billion. Health interventions can yield economic benefits by preventing exits from the labour market due to health issues and reducing medical and long-term care costs.


Modified pore canals in the cuticle of Gammarus (Crustacea : Amphipoda); a study by scanning and transmission electron microscopy.
A novel type of pore canal is described from the cuticle of three species of Gammarus. Each canal passes from the epidermis vertically through the endocuticle and exocuticle, and in the most distal layers of the latter is slightly expanded. Before entering the epicuticle the canal narrows, forming a neck the base of which is encircled by an electron-dense collar. Several tubular structures arise from the collar and pass distally into the reticular innermost regions of the epicuticle. Within the neck and just below its opening at the cuticle surface, a rod-like structure is inserted; this protrudes a short distance from the pore. Each pore canal is connected to many necks; the openings of the latter are aligned in rows over the surface, the openings and rows being about 0.15 and 1.0 micron apart, respectively. Changes in the pore and canal contents are visible and their significance is discussed.


Vaccinia specific kinase inhibitory factor prevents translational inhibition by double-stranded RNA in rabbit reticulocyte lysate.
Mouse L-cells infected with vaccinia virus produce a specific kinase inhibitory factor (SKIF) which inhibits the activation of the interferon-induced, double-stranded (ds)RNA-dependent, eukaryotic initiation factor (eIF)-2 alpha-specific protein kinase in L-cell extracts (Whitaker-Dowling, P., and Younger, J. S., (1984) Virology 137, 171). The effects of a partially purified preparation of SKIF have been examined in cell-free extracts of rabbit reticulocytes. Both the phosphorylation state of eIF-2 and protein synthetic activity have been determined. SKIF inhibits the phosphorylation of the alpha subunit of eIF-2 by dsRNA-dependent eIF-2 alpha-kinase in reticulocyte lysate, but does not affect phosphorylation of eIF-2 by the heme-sensitive kinase. In addition to its effects on eIF-2 alpha-PKds activity, SKIF prevents dsRNA-induced inhibition of protein synthesis in reticulocyte lysate. In contrast, SKIF does not prevent the translational inhibition caused by hemin depletion. These data provide a direct correlation between the effects of SKIF on eIF-2 alpha phosphorylation and on protein synthetic activity and demonstrate the specificity of SKIF. The results also show that SKIF does not abolish dsRNA sensitivity, but increases the concentration of dsRNA required to activate the kinase and phosphorylate eIF-2.


Older persons' definitions of good health: implications for general practitioners.
General practitioners are the major providers of health-care services for the older population in Australia. Care that is provided for older persons within the general-practice setting remains crisis-orientated. Nevertheless, many of the disabling health problems of older persons neither can be "solved" nor cured. Therefore, the older population is a unique population in which to study what constitutes good health and ways in which good health can be maintained. This article describes the perceptions of a group of older persons about their health. They define good health in a remarkably non-medical way. General practitioners need to take into account this knowledge when considering ways to improve the health of these patients.