Kinematics of arm joint rotations in cerebellar and unskilled subjects associated with the inability to throw fast.
Cerebellar subjects and unskilled throwers cannot produce fast arm movements when throwing. We investigated the arm movement kinematics associated with this lack of skill. Cerebellar subjects and matched controls, and skilled throwers throwing with their skilled (dominant) and unskilled (nondominant) arms, were instructed to make slow, medium, and fast 3-D overarm throws from a sitting position. Only the fast throws were analyzed in detail. Joint motions were computed from angular positions of arm segments recorded with search coils. When throwing, both the cerebellar group and the unskilled-arm group had slower arm movements, and slower elbow extension and wrist flexion velocities than their reference groups. They also had similar magnitudes of many kinematic parameters, e.g., both cerebellar and unskilled groups had similar elbow extension and wrist flexion velocities. Compared to their reference groups, both the cerebellar and unskilled-arm groups also had a smaller elbow extension acceleration, a smaller shoulder adduction deceleration, and the absence of a large elbow extension deceleration before ball release. Similar decreases in joint velocities and in joint accelerations and decelerations in the cerebellar and unskilled groups are consistent with the idea that the absence of the skill of throwing fast in both groups is associated with an inability to exploit interaction torques.


Intrauterine inflammation induces sex-specific effects on neuroinflammation, white matter, and behavior.
Exposure to inflammation during pregnancy has been linked to adverse neurodevelopmental consequences for the offspring. One common route through which a developing fetus is exposed to inflammation is with intrauterine inflammation. To that end, we utilized an animal model of intrauterine inflammation (IUI; intrauterine lipopolysaccharide (LPS) administration, 50µg, E15) to assess placental and fetal brain inflammatory responses, white matter integrity, anxiety-related behaviors (elevated zero maze, light dark box, open field), microglial counts, and the CNS cytokine response to an acute injection of LPS in both males and females. These studies revealed that for multiple endpoints (fetal brain cytokine levels, cytokine response to adult LPS challenge) male IUI offspring were uniquely affected by intrauterine inflammation, while for other endpoints (behavior, microglial number) both sexes were similarly affected. These data advance our understanding of sex-specific effects of early life exposure to inflammation in a translationally- relevant model.


Alzheimer's Disease: A Journey from Amyloid Peptides and Oxidative Stress, to Biomarker Technologies and Disease Prevention Strategies-Gains from AIBL and DIAN Cohort Studies.
Worldwide there are over 46 million people living with dementia, and this number is expected to double every 20 years reaching about 131 million by 2050. The cost to the community and government health systems, as well as the stress on families and carers is incalculable. Over three decades of research into this disease have been undertaken by several research groups in Australia, including work by our original research group in Western Australia which was involved in the discovery and sequencing of the amyloid-β peptide (also known as Aβ or A4 peptide) extracted from cerebral amyloid plaques. This review discusses the journey from the discovery of the Aβ peptide in Alzheimer's disease (AD) brain to the establishment of pre-clinical AD using PET amyloid tracers, a method now serving as the gold standard for developing peripheral diagnostic approaches in the blood and the eye. The latter developments for early diagnosis have been largely achieved through the establishment of the Australian Imaging Biomarker and Lifestyle research group that has followed 1,100 Australians for 11 years. AIBL has also been instrumental in providing insight into the role of the major genetic risk factor apolipoprotein E ɛ4, as well as better understanding the role of lifestyle factors particularly diet, physical activity and sleep to cognitive decline and the accumulation of cerebral Aβ.


The recurrent campylobacteriosis epidemic over Christmas and New Year in European countries, 2006-2014.
Campylobacteriosis is the most frequently reported foodborne disease in Europe with a notification rate of 71 per 100,000 population in the European Union in 2014. Surveillance data show a clear seasonality whereby case numbers peak during summer months in entire Europe and at the turn of the year, especially in Germany and Switzerland. A detailed description of European surveillance data by country at the turn of the year was missing so far. The objectives of the presented work were to describe national surveillance data of The European Surveillance System for 14 countries during winter times and to generate hypotheses for the observed seasonality of campylobacteriosis cases. The analysis included 317,986 cases notified between calendar weeks 45 and 8 of winter seasons 2006/2007-2013/2014. Winter peaks in weekly case notifications and notification rates were observed for Austria, Belgium, Finland, Germany, Luxembourg, The Netherlands, Switzerland and Sweden while for Denmark, France, Ireland, Italy, Norway and the United Kingdom no unusual increase was observed. Generally, weekly notification rates peaked in calendar week 1 or 2 after a strong decline in the last week of December and reached values of a multiple of the observed notification rates in the weeks before or after the peak e.g. up to 6.5 notifications per 100,000 population per week in Luxembourg. Disease onset of cases notified during winter peaks occurred predominantly in calendar weeks 52 and 1 and point towards risk exposures around Christmas and New Year. The consumption of meat fondue or table top grilling poses such a risk and is popular in many countries with an observed winter peak. Additionally, increased travel activities over the festive season could foster campylobacteriosis transmission. Surveillance artefacts (e.g. reporting delays due to public holidays) should be excluded as causes for country-specific winter peaks before investigating risk exposures.


Treatment of comorbidity in conduct disorder with attention-deficit hyperactivity disorder (ADHD).
Conduct disorder (CD) is one of the most common psychiatric disorders in childhood and adolescence. It is characterized by a variety of chronic antisocial behaviors, a repetitive and persistent pattern of behavior that violates the basic rights of others, major age-appropriate societal norms, or both. Aggressive behavior, lying, stealing, fire-setting, and running away from home and school are the most frequent manifestations of CD and are often accompanied by hyperactivity, impulsive behavior, explosiveness, cognitive and learning problems, and poor social skills. The rate of comorbidity is high, with attention-deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) being the most common; comorbid anxiety and depressive disorders are also seen, especially in adolescents. The diagnostic process should include the use of structured interviews, and scores from reliable and valid rating scales that cover all psychiatric disorders must be considered in the differential diagnosis, because CD alone is an extreme rarity and multiple disorders are almost always the rule rather than exception. Treatment should include parenting skills training combined with training of the child to improve his or her relationships with peers, academic performance, and compliance with legitimate demands of authority figures. The appropriate use of medications and integration of patient/parent education and support, as well as individual, group, family, residential, and inpatient treatment may be beneficial for patients with CD and ADHD. The article describes a number of psychopharmacological agents that are used in patients with CD with ADHD and other comorbid disorders. Drugs that may be useful include psychostimulants; atomoxetine (Strattera); antidepressants (imipramine [Tofranil], desipramine [Norpramin]); Selective Serotonin Reuptake Inhibitors (SSRIs); atypical antipsychotics such as risperidone (Risperdal); or mood regulators including lithium (Eskalith).


Surgical treatment of right ventricular hydatid cyst.
Hydatid cyst is a serious endemic parasitic disease found in cattle-raising areas of the world. Cardiac hydatid cysts are rare and appear in 0.5% to 2% of hydatid cyst cases. A 24-year-old male patient was admitted to the hospital because of chest pain. A cystic mass (4 4 3 cm) was demonstrated with transthoracic echocardiography, computed tomography, and magnetic resonance imaging. A hydatid cyst was located in the right ventricular wall near the inferior branch of the acute marginal branch of the right coronary artery and was located such that it pushed the tricuspid valve inward. The cystic materials were removed with the patient on cardiopulmonary bypass. The surgery for cardiac hydatid disease is safe, and the results are satisfactory.


Pre-pregnancy BMI, gestational weight gain and postpartum weight retention: a meta-analysis of observational studies.
To determine the association of gestational weight gain (GWG) or pre-pregnancy BMI with postpartum weight retention (PPWR). Meta-analysis. PubMed, Cochrane Controlled Trials Register, EMBASE, Science Citation Index Expanded, Current Contents Connects and Biosis Previews were used to search articles. Publications that described the influence of pre-pregnancy BMI or GWG on PPWR. Seventeen studies that satisfied the eligibility criteria were included in the analyses. Women with inadequate and excessive GWG had significantly lower mean PPWR of -2·14 kg (95 % CI -2·43, -1·85 kg) and higher PPWR of 3·21 kg (95 % CI 2·79, 3·62 kg), respectively, than women with adequate GWG. When postpartum time spans were stratified into 1-3 months, 3-6 months, 6-12 months, 12-36 months and ≥15 years, the association between inadequate GWG and PPWR faded over time and became insignificant (-1·42 kg; 95 % CI -3·08, 0·24 kg) after ≥15 years. However, PPWR in women with excess GWG exhibited a U-shaped trend; that is, a decline during the early postpartum time span (year 1) and then an increase in the following period. Meta-analysis of qualitative studies showed a significant relationship between excessive GWG and higher PPWR risk (OR=2·08; 95 % CI 1·60, 2·70). Moreover, meta-analysis of pre-pregnancy BMI on PPWR indicated that mean PPWR decreased with increasing BMI group. These findings suggest that GWG, rather than pre-pregnancy BMI, determines the shorter- or longer-term PPWR.


Natriuretic hormone.
The factors that control sodium excretion have been the subject of considerable work in recent years. The natriuresis that follows expansion of the extracellular fluid volume is mediated to a large extent by inhibition of tubular sodium reabsorption. Of the several mechanisms proposed to explain this inhibition, considerable interest has followed the suggestion that a humoral substance is released into the blood stream in response to volume expansion. The present article reviews the evidence for and against the existence of such a humoral substance (natriuretic hormone). It also discusses its proposed chemical nature and its possible site of origin in the organism as well as its mode of action.


Metabolic (Bariatric and Nonbariatric) Surgery for Type 2 Diabetes: A Personal Perspective Review.
: Metabolic surgery can cause amelioration, resolution, and possible cure of type 2 diabetes. Bariatric surgery is metabolic surgery. In the future, there will be metabolic surgery operations to treat type 2 diabetes that are not focused on weight loss. These procedures will rely on neurohormonal modulation related to the gut as well as outside the peritoneal cavity. Metabolic procedures are and will always be in flux as surgeons seek the safest and most effective operative modality; there is no enduring gold standard operation. Metabolic bariatric surgery for type 2 diabetes is more than part of the clinical armamentarium, it is an invitation to perform basic research and to achieve fundamental scientific knowledge.


Ultrasound-guided aspiration of hydrosalpinges is associated with improved pregnancy and implantation rates after in-vitro fertilization cycles.
Previous reports have shown that the presence of hydrosalpinges may have a detrimental effect on in-vitro fertilization (IVF) outcomes and salpingectomy has been recommended by some authors as a means of improving IVF pregnancy rates. Our first objective was to determine the effect of hydrosalpinges diagnosed by ultrasound on IVF outcomes in our clinic. Our second objective was to examine the effects of aspiration of hydrosalpinges at the time of oocyte retrieval on IVF outcomes. Women with hydrosalpinges (n=34) were compared with women who had tubal disease but no hydrosalpinges (n=124) and were found to have a reduced clinical pregnancy rate (18 % versus 37%, P=0.053), a reduced ongoing pregnancy rate (15 versus 34%, P=0.051), and a reduced implantation rate (7 versus 18%, P=0.003) after IVF procedures. Among women with hydrosalpinges present, 16 had their hydrosalpinges aspirated at the time of oocyte retrieval and 18 did not. Aspiration of hydrosalpinges was associated with a higher clinical pregnancy rate (31 versus 5%, P=0.07), a higher ongoing pregnancy rate (31 versus 0%, P=0.015), and a higher implantation rate (14 versus 1%, P=0.015). This study confirms the association between the presence of hydrosalpinges and poor IVF outcomes. We find that aspiration of hydrosalpinges at the time of oocyte retrieval leads to improved pregnancy rates and may be an acceptable alternative to salpingectomy for treatment of these patients.


The effects of Baduanjin exercise vs. brisk walking on physical fitness and cognition in middle-aged patients with schizophrenia: A randomized controlled trial.
Patients with schizophrenia have deficits in physical and cognitive function that may become salient in their middle ages. These deficits need active intervention to prevent functional decline. Baduanjin and brisk walking show promise as interventions in patients with schizophrenia. This study investigated the effects of Baduanjin exercise vs. brisk walking in middle-aged patients with schizophrenia. In this single-blind, 2-arm, parallel, randomized controlled trial, 48 participants aged older than 40 years were enrolled and assigned to the intervention group (Baduanjin) or the control group (brisk walking). The training of both groups took place twice a week, 60 min per session, for 12 weeks. The participants were evaluated with physical, cognitive, and functional outcomes at baseline, postintervention, and 4 weeks after the intervention. The results of the study demonstrated significant time effects in walking distance (p = 0.035, η2 = 0.094) and lower extremity strength (p = 0.006, η2 = 0.152). Post-hoc analysis revealed both groups had significant improvement in changes from baseline to the postintervention assessment (ps < 0.05) and follow-up (ps < 0.05). The results demonstrated a significant group-by-time interaction in change scores of global cognition (F = 7.01, p = 0.011, η2 = 0.133). Post-hoc analysis revealed a significant improvement in the Baduanjin group from baseline to postintervention (p = 0.021), but the improvements were not maintained at the follow-up assessment (p = 0.070). The results also demonstrated significant group effects in balance function (p < 0.001, η2 = 0.283), motor dual-task performance (p = 0.026, η2 = 0.103), and cognitive dual-task performance (p < 0.001, η2 = 0.307). Post-hoc analysis revealed that the Baduanjin group improved more than the brisk walking group in the above outcomes (ps < 0.05). This study demonstrated the differential effects of Baduanjin exercise and brisk walking in middle-aged patients with schizophrenia. Baduanjin might be a beneficial regimen for improving physical and cognitive function in this population. Further research with a larger sample is warranted. [ClinicalTrials.gov], identifier [202000817B0C602].


General and violent recidivism of former forensic psychiatric patients in Finland.
Forensic psychiatric care in Finland is provided to individuals who have committed a crime due to a serious mental disorder and are in need of psychiatric care. The reconviction (recidivism) rates for this patient group vary in time and between countries, likely due to different treatment practices and requirements for forensic care. We set out to study criminal recidivism in a national cohort of all patients released from forensic psychiatric care in Finland between 1999 and 2018. National registries were used to identify the patients and gain information on their criminal sentences. Forensic psychiatric examinations were used to record demographic information for the cohort. The cohort was followed up from hospital discharge to the end of 2019. We identified a total of 501 patients who were released from forensic psychiatric care (mean age: 46.6 years [SD 13.4), 434 (86.6%) were male). The mean and median times spent in treatment for the cohort was 10.0 years [SD 6.5] and 8.7 years, respectively. 91% of the patients had schizophrenia spectrum disorder (F2*), and 63.5% had a substance use disorder. A total of 83 patients (16.6%) committed any crime after being released from care, and the mean time to recidivism was 3.8 years. The recidivism rate was 2015 per 100,000 person years. A total of 48 patients (9.6%) committed a violent crime. The mean time to violent recidivism was 4.2 years. The violent recidivism rate was 1,083 per 100,000 person years. A longer duration of treatment was associated with a decreased risk of general recidivism (HR 0.95, 95% CI 0.90 to 1.00, p = 0.05). Factors associated with higher recidivism were male sex, having a comorbid substance use disorder and younger age at discharge. The recidivism rate in Finland was markedly lower than has been previously reported for other Western countries, and the mean duration of treatment was also longer. A longer treatment time may reduce the risk of criminal recidivism in forensic psychiatric patients. The results suggest, as previous studies have found, that more effort is indicated on the treatment of substance abuse.


A multifaceted independent performance analysis of facial subspace recognition algorithms.
Face recognition has emerged as the fastest growing biometric technology and has expanded a lot in the last few years. Many new algorithms and commercial systems have been proposed and developed. Most of them use Principal Component Analysis (PCA) as a base for their techniques. Different and even conflicting results have been reported by researchers comparing these algorithms. The purpose of this study is to have an independent comparative analysis considering both performance and computational complexity of six appearance based face recognition algorithms namely PCA, 2DPCA, A2DPCA, (2D)(2)PCA, LPP and 2DLPP under equal working conditions. This study was motivated due to the lack of unbiased comprehensive comparative analysis of some recent subspace methods with diverse distance metric combinations. For comparison with other studies, FERET, ORL and YALE databases have been used with evaluation criteria as of FERET evaluations which closely simulate real life scenarios. A comparison of results with previous studies is performed and anomalies are reported. An important contribution of this study is that it presents the suitable performance conditions for each of the algorithms under consideration.


Developmental and molecular response of bovine embryos to reduced nutrients in vitro.
Recent studies in our laboratory have indicated that bovine embryos only use a small amount of the nutrients available to them in culture. Our objective was to evaluate the developmental and molecular response of bovine embryos when nutrient concentrations in the culture medium were significantly reduced. Following IVM and IVF, embryos were cultured in media containing 75, 50, and 25% (experiment 1) or 25, 12.5, and 6.25% (experiment 2) of the concentrations of nutrients (carbohydrates, amino acids, and vitamins) present in our control medium (100%). Blastocyst formation, hatching, and allocation of cells to the inner cell mass (ICM) and trophectoderm (TE) were evaluated on day 7. Although the number of TE cells was decreased (P < 0.05) when nutrient concentrations were ≤25% (73.8-124.1 cells), it was not until nutrient concentrations were reduced to 6.25% that blastocyst formation (18.3 ± 3.0%) and hatching (3.0 ± 1.3%) were inhibited (P < 0.05) compared to embryos cultured in the control medium (156.1 ± 14.1 cells, 40.0 ± 3.8%, 20.0 ± 3.1%, respectively). Inhibition of fatty acid oxidation (etomoxir) reduced (P < 0.05) blastocyst development, with more pronounced effects at lower nutrient concentrations (≤12.5%). Reducing nutrient concentrations was associated with increased activity of AMPK, decreased activity of mTOR, and altered abundance of transcripts for hexokinase 1 (HK1), carnitine palmitoyl transferase 2 (CPT2), lactate dehydrogenase A (LDHA), and pyruvate dehydrogenase kinase 1 (PDK1), consistent with an increase in glucose and fatty acid metabolism. Reduced nutrient conditions provide a unique perspective on embryo metabolism that may facilitate the optimization of culture media. To support early embryo development in the first week after fertilisation, an appropriate mixture of nutrients (carbohydrates, amino acids, and vitamins) is needed in the culturing solution. However, refining these solutions to support optimal embryo health remains challenging. In this study, bovine (cow) embryos derived from abattoir material were used as a model for the development of other mammalian embryos, including humans. These embryos were cultured in the presence of 75, 50, 25, 12.5, or 6.25% of the nutrients present in control conditions (100%), which are similar to those reported for the fluids of the fallopian tubes and uterus. Embryo development was largely unaffected in the 75, 50, and 25% treatments, with some embryos developing in the presence of only 6.25% nutrients. Cow embryos are remarkably resilient to reduced concentrations of nutrients in their environment because they can utilize internal stores of fat as a source of energy.


Lung Abscess in Critically Ill Coronavirus Disease 2019 Patients With Ventilator-Associated Pneumonia: A French Monocenter Retrospective Study.
The pulmonary vascular endothelialitis together with the high rate of distal pulmonary embolism or thrombosis extensively reported in critically ill coronavirus disease 2019 patients may impair antibiotic diffusion in the lung parenchyma of coronavirus disease 2019 patients with ventilator-associated pneumonia leading to insufficient antibiotic concentration, thus promoting lung abscess formation. We report that 17 of 119 coronavirus disease 2019 patients (14%) with ventilator-associated pneumonia developed a lung abscess. Proportion of patients receiving corticosteroids did not differ between patients with and without lung abscess. Most of lung abscess were polymicrobial. Enterobacteriaceae, Pseudomonas aeruginosa, and Staphylococcus aureus were the leading causative bacteria. Most of lung abscesses involved the right lower lobe. Three patients had concomitant pulmonary embolism or thrombosis in the territory of lung abscess. Lung abscess was retrospectively visible on chest radiograph in 29% of the patients. As the occurrence of lung abscess impacts the duration of antibiotics therapy, chest CT scan should be easily performed in case of treatment failure of ventilator-associated pneumonia despite adequate antimicrobial therapy.


The molecular mechanisms of a novel multi-kinase inhibitor ZLJ33 in suppressing pancreatic cancer growth.
ZLJ33, an oral active multi-kinase inhibitor, was evaluated both in vitro and in vivo against human pancreatic cancer. It could effectively inhibit cell proliferation, induce apoptosis, and cause inhibition of invasion in pancreatic cancer cells. At a dose of 15.0 mg/kg, ZLJ33 induced tumor shrink in Mia-PaCa2, Capan2, and AsPC-1 xenografts models by 60.59%, 74.19%, and 71.54% according to the tumor weight, respectively. The effect of ZLJ33 on pancreatic cancer was mainly mediated by inactivation of p-PDGFRβ, p-c-Raf, and p-RET. Treatment with ZLJ33 did not cause side effect of hematology indexes in the pancreatic cancer xenograft model. ZLJ33 could be a potential therapeutic agent against pancreatic cancer.


A filtered backprojection algorithm with ray-by-ray noise weighting.
This paper derives a ray-by-ray weighted filtered backprojection (rFBP) algorithm, based on our recently developed view-by-view weighted, filtered backprojection (vFBP) algorithm. The rFBP algorithm directly extends the vFBP algorithm by letting the noise weighting vary from channel to channel within each view. The projection data can be weighted in inverse proportion to their noise variances. Also, an edge-preserving bilateral filter is suggested to perform post filtering to further reduce the noise. The proposed algorithm has been implemented for the circular-orbit cone-beam geometry based on Feldkamp's algorithm. Image reconstructions with computer simulations and clinical cadaver data are presented to illustrate the effectiveness and feasibility of the proposed algorithm. The new FBP-type algorithm is able to significantly reduce or remove the noise texture, which the conventional FBP is unable to do. The computation time of the proposed rFBP algorithm is approximately the same as the conventional FBP algorithm. A ray-based noise-weighting scheme is introduced to the FBP algorithm. This new FBP-type algorithm significantly reduces or removes the streaking artifacts in low-dose CT.


Long-term Effects of IL-6 Receptor Blockade Therapy on Regulatory Lymphocytes and Neutrophils in Neuromyelitis Optica Spectrum Disorder.
Neuromyelitis optica spectrum disorder (NMOSD) is a disabling autoimmune neurologic disease. Anti-IL-6 receptor (IL-6R) therapy prevents relapses in patients with anti-aquaporin 4 (AQP4)-IgG-positive NMOSD; however, it remains unclear how cellular immune components are altered by anti-IL-6R therapy. In this study, we examined the long-term effects of the anti-IL-6R monoclonal antibody tocilizumab (TCZ) on immune cell profiles in patients with NMOSD. Monthly IV injections of TCZ (8 mg/kg) were administered as an add-on therapy to 19 anti-AQP4-IgG-positive patients, who had been refractory to corticosteroids and immunosuppressive drugs. Peripheral blood was collected before infusion of TCZ for flow cytometry analysis of lymphocyte subsets. Seven patients provided whole blood samples for gene expression profiles. Patients with NMOSD had reduced numbers of lymphocyte subsets with regulatory functions, including transitional B cells, CD56high NK cells, and CD45RA-FoxP3high regulatory T cells. However, after initiating TCZ therapy, the numbers increased to normal levels within 1 year. Gene expression analysis revealed that neutrophil granule-related genes, predominated by those related to azurophil granules, were significantly upregulated in patients with NMOSD. Such alterations suggestive of accelerated myeloid turnover were not observed 1 year after TCZ therapy, and the effects of TCZ on some neutrophil genes were observed as early as 5 days after starting TCZ. In vitro analysis demonstrated that naïve T-cell division was impaired in the enrolled patients, which was fully recovered after 18 months of therapy. In patients with active NMOSD not treated with molecular targeting drugs, we observed reduction or deficiency in lymphocytes with regulatory potentials and activation of neutrophils. However, introduction of anti-IL-6R therapy accompanied by tapering concomitant drugs corrected such abnormalities, which might contribute to persistent relapse prevention. The recovery in the naïve T-cell division after starting TCZ may underlie the relatively low risk of infection in patients under anti-IL-6R therapy. University Hospital Medical Information Network Clinical Trials Registry: UMIN000005889 (July 8, 2011) and UMIN000007866 (May 1, 2012) (umin.ac.jp/ctr/index.htm). The first participant was enrolled on November 2, 2011.


Temperature- and chemical-induced neurotoxicity in zebrafish.
Throughout their lives, humans encounter a plethora of substances capable of inducing neurotoxic effects, including drugs, heavy metals and pesticides. Neurotoxicity manifests when exposure to these chemicals disrupts the normal functioning of the nervous system, and some neurotoxic agents have been linked to neurodegenerative pathologies such as Parkinson's and Alzheimer's disease. The growing concern surrounding the neurotoxic impacts of both naturally occurring and man-made toxic substances necessitates the identification of animal models for rapid testing across a wide spectrum of substances and concentrations, and the utilization of tools capable of detecting nervous system alterations spanning from the molecular level up to the behavioural one. Zebrafish (Danio rerio) is gaining prominence in the field of neuroscience due to its versatility. The possibility of analysing all developmental stages (embryo, larva and adult), applying the most common "omics" approaches (transcriptomics, proteomics, lipidomics, etc.) and conducting a wide range of behavioural tests makes zebrafish an excellent model for neurotoxicity studies. This review delves into the main experimental approaches adopted and the main markers analysed in neurotoxicity studies in zebrafish, showing that neurotoxic phenomena can be triggered not only by exposure to chemical substances but also by fluctuations in temperature. The findings presented here serve as a valuable resource for the study of neurotoxicity in zebrafish and define new scenarios in ecotoxicology suggesting that alterations in temperature can synergistically compound the neurotoxic effects of chemical substances, intensifying their detrimental impact on fish populations.


Trifolium repens L.-Like Periodic Micronano Structured Superhydrophobic Surface with Ultralow Ice Adhesion for Efficient Anti-Icing/Deicing.
Wind turbine blades are often covered with ice and snow, which inevitably reduces their power generation efficiency and lifetime. Recently, a superhydrophobic surface has attracted widespread attention due to its potential values in anti-icing/deicing. However, the superhydrophobic surface can easily transition from Cassie-Baxter to Wenzel at low temperature, limiting its wide applications. Herein, inspired by the excellent water resistance and cold tolerance of Trifolium repens L. endowed by its micronano structure and low surface energy, a fresh structure was prepared by combining femtosecond laser processing technology and a boiling water treatment method. The prepared icephobic surface aluminum alloy (ISAl) mainly consists of a periodic microcrater array, nonuniform microclusters, and irregular nanosheets. This three-scale structure greatly promotes the stability of the Cassie-Baxter state. The critical Laplace pressure of ISAl is up to 1437 Pa, and the apparent water contact angle (CA) is higher than 150° at 0 °C. Those two factors contribute to its excellent anti-icing and deicing performances. The results show that the static icing delay time reaches 2577 s, and the ice adhesion strength is only 1.60 kPa. Furthermore, the anti-icing and deicing abilities of the proposed ISAl were examined under the environment of low temperature and high relative humidity to demonstrate its effectiveness. The dynamic anti-icing time of ISAl in extreme environments is up to 5 h, and ice can quickly fall with a speed of 34 r/min when it is in a horizontal rotational motion. Finally, ISAl has excellent reusability and mechanical durability, with the ice adhesion strength still being less than 6 kPa and the CA greater than 150° after 15 cycles of icing-deicing tests. The proposed structure would offer a promising strategy for the efficient anti-icing and deicing of wind turbine blades.


Predictive Validity of Some Common Animal Models of Bipolar Disorder Using Lithium and Lamotrigine Therapy: An Attempt towards a Battery-Based Approach for the Evaluation of Mood Stabilizers.
To determine the predictive validity of some of the commonly employed models of mania and depression using standard drugs i.e. lithium (70 mg/kg) and lamotrigine (5 mg/kg) in male Wistar rats. The depression facet of bipolar disorder was evaluated using forced swim test, tail suspension test, and chronic mild stress test. The models used to evaluate the mania facet of bipolar disorder were isolation-induced aggression test, saccharine preference test, and morphine-sensitized hyperlocomotion test. The immobility time was significantly (p<0.05) reduced by lamotrigine in the tail suspension test and the forced swim test, while lithium caused significant (p<0.05) reduction only in the tail suspension test. Rats exposed to chronic mild stress showed the maximal increment of 1% sucrose consumption at the 3rd week of treatment in both the lithium (p<0.001) and lamotrigine (p<0.01) groups. In the isolation-induced aggression test, the aggressive behaviour of rats was significantly reduced by both lithium [approach (p<0.001), attack (p<0.01), and bite (p<0.01)] and lamotrigine [approach (p<0.001), and attack (p<0.05)]. Neither of the drugs were effective in the saccharine preference test. Only lithium was able to significantly (p<0.05) reduce the crossing parameter in morphine-sensitized rats. Our study identifies the chronic mild stress test and isolation-induced aggression test of having the highest predictive validity in the depression and mania facets of bipolar disorder, respectively, and should be a part of a battery of tests used to evaluate novel mood stabilizers.


The bovine dominant ovarian follicle.
Central roles in reproductive biology (i.e., growth and development of the oocyte, steroidogenesis, and ovulation) are played by the ovarian dominant follicle (DF). The DF is different from other follicles because it can escape atresia (the fate of all other follicles), and if exposed to the LH surge, its cells will differentiate into the corpus luteum. The DF was originally studied by looking at the surface of ovary through a surgical approach. Current studies employ a less-invasive ultrasound technique to track the growth and development of the DF. Recruitment and selection, the processes that give rise to the DF, and dominance, the physiological state of the mature DF, are important areas of basic research. Results of these basic studies are easily translated into real-world problems in farm animal reproduction. Superovulation, for example, overrides the selection mechanism and increases the number of ovulations. Understanding the factors that affect the size of the recruited pool should increase success rates (i.e., number of collected embryos) for superovulation. In most animals, the DF is short-lived, existing for long enough to allow for the final maturation of the oocyte. Some DF become atretic because they mature during the luteal phase and are never exposed to the LH surge. For other DF, the LH surge redirects the DF toward its ultimate demise (i.e., luteinization, ovulation, and differentiation into the corpus luteum). The DF is managed pharmacologically within protocols for timed AI. When timed AI fails, there may be abnormal corpus luteum development and early embryonic loss; outcomes that are secondary to inadequate follicular cell maturation and incomplete oocyte capacitation in the DF. Future work on the DF will clarify its underlying biological functions so that a variety of needs in farm animal reproduction can be efficiently managed.


What do citation counts count for in the field of addiction? An empirical evaluation of citation counts and their link with peer ratings of quality.
This study investigated the value of citation counts as an index of quality in the field of addiction and examined factors that contribute to papers being cited more or less frequently. The number of times papers published by the journal Addiction in 1995-98 that had been cited up to May 2000 were counted using the Science and the Social Science Citation Indexes. Articles in nine of the monthly issues from 1997 were rated by two independent expert raters for quality. Factors related to citation counts were also examined including: country of origin of the paper, substance type, solicited versus unsolicited papers and methodology used. A total of 417 unsolicited research reports were included in the citation analysis, of which 79 were also subjected to quality ratings. The experts showed a moderate level of agreement in their ratings (intraclass correlation = 0.39. p < 0.001). However, there was no correlation between number of citations and expert ratings of article quality (R < 0.1). Papers from developing countries received significantly fewer citations than papers from other countries but substance type (e.g. nicotine, opiate, alcohol) and methodology (e.g. survey, treatment trial) were not related to number of citations. This study involved just one journal but raised an important issue: the number of citations received by papers on addiction appears to reflect the geographical region of study rather than what experts would consider as 'quality'. If these findings are found to generalize they call into question the use of citation-related indices as measures of quality in this field and perhaps in others as well. To our knowledge our methodology has not been used before and could be adapted to study the value of citations more widely.


Gait patterns during different walking conditions in older adults with and without knee osteoarthritis--results from the Baltimore Longitudinal Study of Aging.
Biomechanical analysis of lower extremity activities while walking at different speeds and in challenging conditions may help to identify specific gait patterns associated with knee osteoarthritis (knee-OA). We hypothesized that individuals with asymptomatic knee-OA have lower ankle activity, while individuals with symptomatic knee-OA have similar or higher ankle activity compared to individuals without knee-OA, and that such differences are enhanced during challenging gait tasks. We tested this hypothesis by examining gait characteristics in multiple gait tasks using data from 153 Baltimore Longitudinal Study of Aging (BLSA) participants (112 without knee-OA, 41 with knee-OA; 53-87 years, 52% women). All participants who could walk unassisted were evaluated in the BLSA gait lab while walking at self-selected speed (usual-walking), at maximum speed (fast-walking) and again at self-selected speed after 30-min of walking activities (usual-walking-after-30 min). Knee range of motion was lower for knee-OA participants in the fast-walking and usual-walking-after-30 min tasks (p<0.030). Ankle range of motion for symptomatic knee-OA was greater compared to asymptomatic knee-OA for all walking tasks (p<0.050). Symptomatic knee-OA had greater generative MWE of the ankle compared to asymptomatic knee-OA (p=0.034), while keeping similar absorptive MWE of the knee when compared to no-OA controls (p=0.151). Symptomatic knee-OA individuals seem to adapt an ankle kinematic gait pattern aimed at avoiding knee pain, by enhancing forward propulsion so to minimize knee joint load. Whether these conditions represent subsequent steps in the causal pathway from knee-OA to changes in gait is still not clear.


Multiplexed, real-time PCR for quantitative detection of human adenovirus.
Adenovirus infection is becoming increasingly recognized as a cause of morbidity and mortality in the immunosuppressed patient population. While early detection and quantitation of adenovirus in peripheral blood has been suggested as a means of directing and monitoring antiviral therapy in these patients, few methods have been published, particularly with respect to viral quantitation. A multiplexed real-time PCR assay was developed that can quantitatively detect a wide range of known serotypes of human adenovirus, including all of subgroups A to C. This assay was compared to a qualitative, Southern blot-based PCR assay by using 45 peripheral blood specimens from 16 patients. There was 100% concordance between the two tests in terms of qualitative results. The real-time assay detected adenovirus in patient samples at levels from <200 to 266,681 copies/ml of blood. By using control viral samples, sensitivity was demonstrated to less than 10 copies of viral genome per reaction and quantitative linearity was demonstrated from 10 to 10(6) copies of input viral DNA. Equivalent sensitivity and linearity were demonstrated for 15 different reference serotypes of adenovirus. Eleven other viral serotypes have complete target region sequence homology to one or more of the strains tested. No cross-reactivity was noted with other commonly isolated viral species. Sequence analysis showed no significant homology with any other human pathogens (bacterial or viral). This assay allows rapid, sensitive, and specific quantitation of adenovirus and may have a significant impact on the care of immunocompromised patients at risk for disseminated viral infection.


Breast Cancer and Exposure to Organochlorines in the CECILE Study: Associations with Plasma Levels Measured at the Time of Diagnosis and Estimated during Adolescence.
Exposure to environmental chemicals with hormonal effects, such as organochlorine compounds (OCs), during developmental periods of breast cells may have an impact on the incidence of breast cancer later in life. However, the assessment of exposure to these chemicals that occurred in early life at the time of breast cancer development in adult women is a difficult challenge in epidemiological studies. Plasma levels of the OCs p,p'-dichlorodiphenyl dichloroethene (DDE) and polychlorinated biphenyl congener 153 (PCB153) were measured in 695 cases and 1055 controls of a population-based case-control study conducted in France (CECILE study). Based on these values, we used a physiologically-based pharmacokinetic (PBPK) model to estimate PCB153 levels at age 11⁻20 years when the women were adolescents. Overall, there was no clear association between breast cancer risk and measured levels of DDE and PCB153 at the time of diagnosis, but there was a trend of decreasing odds ratios of breast cancer with increasing DDE and PCB153 levels in women aged 50 years and over. The PBPK model revealed that PCB153 concentrations estimated during adolescence were highest in the youngest women born after 1960 who reached adolescence at a time when environmental contamination was maximum, and very low in the oldest women who attained adolescence before the contamination peak. Negative associations between breast cancer and PCB153 estimates during adolescence were also found. The negative associations between DDE and PCB153 levels measured at the time of diagnosis or estimated during adolescence in our study were unexplained. Further investigations are needed to clarify whether this finding is real or related to study artifacts. However, this study suggests that using PBPK models in epidemiological studies to back-estimate OC exposures during early life stages may be useful to address critical questions on cancer development.


Topological sensitivity analysis for systems biology.
Mathematical models of natural systems are abstractions of much more complicated processes. Developing informative and realistic models of such systems typically involves suitable statistical inference methods, domain expertise, and a modicum of luck. Except for cases where physical principles provide sufficient guidance, it will also be generally possible to come up with a large number of potential models that are compatible with a given natural system and any finite amount of data generated from experiments on that system. Here we develop a computational framework to systematically evaluate potentially vast sets of candidate differential equation models in light of experimental and prior knowledge about biological systems. This topological sensitivity analysis enables us to evaluate quantitatively the dependence of model inferences and predictions on the assumed model structures. Failure to consider the impact of structural uncertainty introduces biases into the analysis and potentially gives rise to misleading conclusions.


Two enzymes concerned in peptide hormone alpha-amidation are synthesized from a single mRNA.
By expressing truncated rat pituitary 'peptidylglycine alpha-amidating enzyme' cDNAs in COS-7 cells, we found that the two reactions concerned in peptide carboxyl-terminal amidation, namely the peptidylglycine alpha-hydroxylation reaction and the peptidyl-hydroxyglycine amidation reaction, were catalyzed by 37- and 53-K proteins, which were derived from the 5'- and 3'-coding sequences, respectively. The full-length cDNA directed the expression of both the 37- and 53-K enzymes, and in the combined presence of the two enzymes the full conversion of a glycine-extended peptide into the amidated product was achieved. These results indicated that two enzymes concerned in peptide hormone alpha-amidation are generated from a common precursor protein encoded by a single mRNA.


Intraoperative Gram's staining of bile as a guide for early selective administration of antibiotics.
A prospective clinicobacteriological study was undertaken in 100 patients undergoing biliary surgery, to assess the influence on the postoperative course of early antibiotic treatment that was instituted in accordance with the results of intraoperative Gram's staining of gallbladder bile. The wound infection rate was found to be 9% and there wee no other septic complications. The sensitivity of Gram's staining as compared with the results of bile cultures was found to be 65.5%. This study provides additional evidence of the value of Gram's staining of bile as a means for the early discovery of pathogens and early institution of antibiotic therapy, both important factors in lowering the rate of infective postoperative complications.


Chondroplast: A new material for eyelid reconstruction.
After tumor excision both lamellae of the eyelid require reconstruction in order to achieve good functional and cosmetic results. The tarsus is replaced either by autologous or heterologous material. We used Chondroplast as a tarsal replacement in 25 patients who had undergone extensive tumor excision. Chondroplast is a beta-irradiated bovine cartilage. A 1-mm-thick lamella is fixed to the rest of the tarsal plate or the canthal tendon and positioned in a preformed pocket or the conjunctiva and a thin layer of orbicularis muscle and skin. All implants took well. Postoperative results, lid closure and cosmetic appearance were excellent. No complications such as infection or loss of the implant occurred. The advantages of Chondroplast are: its availability in large pieces, no need for harvesting procedures and good biocompatibility.


The psychological effects of nursing interventions on patients with suspected COVID-19 during isolation.
To investigate the psychological characteristics of patients with suspected coronavirus disease 2019 (COVID-19) during isolation and to evaluate the effects of psychological nursing interventions. A total of 137 patients with suspected COVID-19 were assessed using the 7-item Generalized Anxiety Disorder Scale (GAD-7), the 9-item Patient Health Questionnaire (PHQ-9), and the Trait Coping Style Questionnaire (TCSQ). Psychological nursing intervention measures were implemented, after which the patients were re-evaluated. Before intervention, the rates of anxiety and depression among the patients with suspected COVID-19 were 46.72% and 48.20%, respectively. After intervention, statistically significant reductions were observed in the GAD-7 and PHQ-9 scores (both P<0.05). Before intervention, the TCSQ positive and negative coping scores were 31.07±5.25 and 28.78±6.72, respectively, compared with 36.40±5.93 and 24.60±5.99, respectively, after intervention; these differences were statistically significant (both P<0.01). Before and after intervention, the patients' GAD-7 and PHQ-9 scores were negatively correlated with the positive coping score but positively correlated with the negative coping score. For COVID-19 or similar public health emergencies, timely and flexible appropriate psychological intervention and counseling is crucial. Correct implementation of psychological intervention methods can effectively relieve patients' negative emotions, and play an important role in assisting patients during the isolation period.


Treatment outcomes and late toxicities of 869 patients with nasopharyngeal carcinoma treated with definitive intensity modulated radiation therapy: new insight into the value of total dose of cisplatin and radiation boost.
This study was to report the long-term outcomes and toxicities of nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). From 2009 to 2010, 869 non-metastatic NPC patients treated with IMRT were retrospectively enrolled. With a median follow-up of 54.3 months, the 5-year estimated local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) were 89.7%, 94.5%, 85.6%, 76.3%, 84.0%, respectively. In locally advanced NPC, gender, T, N, total dose of cisplatin more than 300 mg/m(2) and radiation boost were independent prognostic factors for DMFS and DFS. Age, T, N and total dose of cisplatin were independent prognostic factors for OS. Radiation boost was an adverse factor for LRFS, RRFS, DMFS and DFS. Concurrent chemotherapy was not an independent prognostic factor for survival, despite marginally significant for DMFS in univariate analysis. Concurrent chemotherapy increased xerostomia and trismus, while higher total dose of cisplatin increased xerostomia and otologic toxicities. In conclusion, IMRT provided satisfactory long-term outcome for NPC, with acceptable late toxicities. Total dose of cisplatin was a prognostic factor for distant metastasis and overall survival. The role of concurrent chemotherapy and radiation boost in the setting of IMRT warrants further investigation.


Biogas residue parameterization for soil organic matter modeling.
A variety of biogas residues (BGRs) have been used as organic fertilizer in agriculture. The use of these residues affects the storage of soil organic matter (SOM). In most cases, SOM changes can only be determined in long-term observations. Therefore, predictive modeling can be an efficient alternative, provided that the parameters required by the model are known for the considered BGRs. This study was conducted as a first approach to estimating the organic matter (OM) turnover parameters of BGRs for process modeling. We used carbon mineralization data from six BGRs from an incubation experiment, representing a range of substrate inputs, to calculate a turnover coefficient k controlling the velocity of fresh organic matter (FOM) decay and a synthesis coefficient η describing the SOM creation from FOM. An SOM turnover model was applied in inverse mode to identify both parameters. In a second step, we related the parameters k and η to chemical properties of the corresponding BGRs using a linear regression model and applied them to a long-term scenario simulation. According to the results of the incubation experiment, the k values ranged between 0.28 and 0.58 d-1 depending on the chemical composition of the FOM. The estimated η values ranged between 0.8 and 0.89. The best linear relationship of k was found to occur with pH (R2 = 0.863). Parameter η is related to the Ct/Norg ratio (R2 = 0.696). Long-term scenario simulations emphasized the necessity of specific k and η values related to the chemical properties for each BGR. However, further research is needed to validate and improve these preliminary results.


Microvascular decompression for neurovascular conflicts in the cerebello-pontine angle: which role for endoscopy?
Microvascular decompression (MVD) is the surgical intervention designed to resolve neurovascular conflicts (NCs) in the cerebellopontine angle (CPA). Today, endoscopy is commonly used in many neurosurgical procedures. This study aims to retrospectively assess the usefulness of endoscopy during MVD, focusing on microscopic endoscopic-assisted (MEA) MVD. Between January 2010 and December 2012, 141 patients underwent MVD procedures: 119 (84.5 %) were affected by idiopathic trigeminal neuralgia (TN), 20 (14 %) by hemifacial spasm (HFS), 1 by glossopharyngeal neuralgia (GN) and 1 by TN and GN simultaneously; 128 (91 %) MVD were first time procedures, while 13 (9 %) were recurrences (10 TN, 3 HFS). Visualization techniques used were: pure microscopic in 89 (63 %) cases, fully endoscopic in 12 (8.5 %) and MEA in 40 (28.5 %). The MEA technique was used when the conflict was not clearly identified under microscopic view or it was not certainly resolved. Overall, a NC was found in 130 (92 %) cases, while 11 patients had no intraoperative evidence of NC. Considering specifically the 40 MEA cases, 12 (8.5 % overall) conflicts not clearly visible with the microscope were revealed and solved, a complete conflict resolution was confirmed in 13 (9 % overall) cases, while an incomplete conflict resolution was shown in four cases (3 % overall). Pure microscopic MVD remains the technique of choice. The endoscope is a useful adjunctive imaging tool in confirming NCs identified by the microscope, revealing conflicts missed by the microscopic survey alone and verifying adequate nerve decompression.


Depression as a major impact on the quality of life of HIV-positive Brazilians.
Given that mental symptoms might interfere with the quality of life (QOL) of people living with HIV/AIDS (PLHAs), the goal of this paper was to examine the correlation between depression, anxiety, and QOL in a sample of HIV-positive Brazilians. A cross-sectional study was designed to analyze the correlations between the presence of mental symptoms and the QOL scores of PLHAs. Depression and anxiety symptoms were measured using the Beck Depression Inventory and the State-Trait Anxiety Inventory, respectively. The QOL was assessed using the World Health Organization Quality of Life instrument - HIV module. A convenience sample of 308 men and women living with HIV (131 asymptomatic, 91 symptomatic, and 86 with AIDS) in Porto Alegre/RS-Brazil was selected. The depression scores were higher in patients with AIDS compared with asymptomatic and symptomatic patients, yet there were no differences in the anxiety scores between the stages of infection. Better QOL scores were observed in the earlier stages of infection (asymptomatic and symptomatic groups). In the correlation between mental symptoms and QOL scores, the Pearson's coefficient values were of a moderate (r = .47) to a large (r = .65) magnitude for depressive symptoms, and the scores for the anxiety symptoms were small to moderate (r ≤ .35). After adjusting for the disease stage and clinical and sociodemographic variables in a multiple regression model (using QOL as the dependent variable), the depressive symptoms showed significantly higher beta-coefficient values compared with the remaining variables. The data obtained from this study indicate that the QOL of PLHAs is primarily affected by depression. Thus, it has been strongly recommended that treatment programs dedicated to PLHAs assess depressive symptoms, providing subsequent referrals and treatments. Treating depression might be effective for PLHAs and might potentially improve both the overall QOL and the health outcomes.


Method of calibration of a fluorescence microscope for quantitative studies.
Confocal microscopy is based on measurement of intensity of fluorescence originating from a limited volume in the imaged specimen. The intensity is quantized in absolute (albeit arbitrary) units, producing a digital 3D micrograph. Thus, one may obtain quantitative information on local concentration of biomolecules in cells and tissues. This approach requires estimation of precision of light measurement (limited by noise) and conversion of the digital intensity units to absolute values of concentration (or number) of molecules of interest. To meet the first prerequisite we propose a technique for measurement of signal and noise. This method involves registration of a time series of images of any stationary microscope specimen. The analysis is a multistep process, which separates monotonic, periodic and random components of pixel intensity change. This approach permits simultaneous determination of dark and photonic components of noise. Consequently, confidence interval (total noise estimation) is obtained for every level of signal. The algorithm can also be applied to detect mechanical instability of a microscope and instability of illumination source. The presented technique is combined with a simple intensity standard to provide conversion of relative intensity units into their absolute counterparts (the second prerequisite of quantitative imaging). Moreover, photobleaching kinetics of the standard is used to estimate the power of light delivered to a microscope specimen. Thus, the proposed method provides in one step an absolute intensity calibration, estimate of precision and sensitivity of a microscope system.


Cascade Reaction of Donor-Acceptor Cyclopropanes: Mechanistic Studies on Cycloadditions with Nitrosoarenes and cis-Diazenes.
Tandem ring opening, elimination, and cycloaddition of donor-acceptor cyclopropanes were observed in Yb(OTf)3-catalyzed cycloaddition with nitrosoarenes. The reaction results in formation of tetrahydro-1,2-oxazine instead of the normal cycloadduct isoxazolidine via in situ nitrone formation. A similar cascade sequence was observed with cis-diazines. Mechanistic studies on this unique transformation offer an entirely new approach for reaction design with donor-acceptor cyclopropanes.


Geographic Distribution of Ammonia-Oxidizing Archaea along the Kuril Islands in the Western Subarctic Pacific.
Community composition and abundance of ammonia-oxidizing archaea (AOA) in the ocean were affected by different physicochemical conditions, but their responses to physical barriers (such as a chain of islands) were largely unknown. In our study, geographic distribution of the AOA from the surface photic zone to the deep bathypelagic waters in the western subarctic Pacific adjacent to the Kuril Islands was investigated using pyrosequencing based on the ammonia monooxygenase subunit A (amoA) gene. Genotypes of clusters A and B dominated in the upper euphotic zone and the deep waters, respectively. Quantitative PCR assays revealed that the occurrence and ammonia-oxidizing activity of ammonia-oxidizing archaea (AOA) reached their maxima at the depth of 200 m, where a higher diversity and abundance of actively transcribed AOA was observed at the station located in the marginal sea exposed to more terrestrial input. Similar community composition of AOA observed at the two stations adjacent to the Kuril Islands maybe due to water exchange across the Bussol Strait. They distinct from the station located in the western subarctic gyre, where sub-cluster WCAII had a specific distribution in the surface water, and this sub-cluster seemed having a confined distribution in the western Pacific. Habitat-specific groupings of different WCB sub-clusters were observed reflecting the isolated microevolution existed in cluster WCB. The effect of the Kuril Islands on the phylogenetic composition of AOA between the Sea of Okhotsk and the western subarctic Pacific is not obvious, possibly because our sampling stations are near to the Bussol Strait, the main gateway through which water is exchanged between the Sea of Okhotsk and the Pacific. The vertical and horizontal distribution patterns of AOA communities among stations along the Kuril Islands were essentially determined by the in situ prevailing physicochemical gradients along the two dimensions.


Properties of human serum low density lipoproteins after modification by succinic anhydride.
Human serum low density lipoprotein of d 1.019-1.063 (LDL(2)) treated with succinic anhydride at pH 7.5-8.0 showed the same chemical composition, hydrodynamic properties (flotation and sedimentation coefficients, intrinsic viscosity) and optical properties (circular dichroism) as untreated LDL(2). However, in contrast to LDL(2), the succinylated product (s-LDL(2)) failed to react with rabbit anti-LDL(2) antisera. Extraction with ethanol-ether 3:1 yielded the succinylated apoprotein (s-apo-LDL(2)), which was, unlike untreated apoprotein, soluble in aqueous buffers. Succinylated apoprotein, which was also immunologically unreactive, appeared to differ in structure from s-LDL(2), as assessed by the parameters of intrinsic viscosity and circular dichroism. The molecular weights of both LDL(2) and s-LDL(2) obtained by the technique of sedimentation equilibrium were 2.1-2.3 x 10(6). By the same method, s-apo-LDL(2) gave an uncorrected figure of 3.95-4.15 x 10(4) and, after correction for succinyl functions, of 3.60-3.80 x 10(4). Because of the assumptions made in the computations, the latter figure was considered approximate. The marked differences in molecular weight between s-apo-LDL(2) and whole apo-LDL(2) ( approximately 5 x 10(5)) were taken to support the subunit structure of apo-LDL(2), which is envisaged as an aggregate of about 12 subunits which dissociate upon succinylation. Further, the large percentage (about 90%) of the free amino groups of LDL(2) found to react with succinic anhydride suggests that these groups are at the surface of the molecule.


The use of body mass changes as a practical measure of dehydration in team sports.
Body mass changes, hematocrit, specific gravity and urine colour were recorded during two games of soccer to determine which of these methods was the most practical in a field setting for monitoring dehydration. Members (n=13) of a premiership soccer team with a mean age of 22.6 (+/-4.9) years old, height of 177.8 (+/-7.1)cm and sum of skinfolds (four sites) of 37 (+/-12.8) were invited to participate in this study with 11 participating in each game. Players had weight, hematocrit, specific gravity and urine colour recorded pre- and post-game. Players were allowed to ingest fluid ad libitum throughout the matches with the amount consumed recorded. Urine excretion was also recorded and included in the calculation of final body mass loss (kg). A mean ambient temperature of 21 degrees C and relative humidity 77% was recorded for both games. Pre- and post-game body mass, sweat loss, hematocrit, urine specific gravity and colour were significantly different (p<0.01) for both games. Linear mixed effects models were fitted to the data in order to identify an optimal prediction equation for sweat loss. The model predicting from mass change was clearly the best fitting. The results demonstrate that a change in body mass during a game of soccer is an effective method of monitoring dehydration due to sweat loss when compared to other known methods that may be invasive and inappropriate in the field.


Pulmonary scarring and its relation to primary lung cancer.
Lung scar carcinoma, so called 'scarcinoma', is a perceived entity that was originally described by Friedrich in 1939, in which a carcinoma originates from peripheral scarring of lung tissue. In a recent pilot study, there was a strong association between the geographic location of lung cancer and the presence of scarring of the lung. To investigate this relationship in the largest cohort to date. We reviewed all radiological images of patients (N=917) with confirmed lung cancer from 2013 - 2017 and included all who had at least a staging computed tomography (CT) of the chest and a tissue diagnosis of primary lung cancer. Two pulmonary specialists categorised all patients as no pulmonary scarring, scarring in the same lobe, scarring in the ipsilateral lung, but not lobe, scarring in the contralateral lung and diffuse scarring both lungs. Almost 1 in 3 patients had pulmonary scarring. In patients with lung cancer, if scarring was present, the pulmonary scarring was more likely to be found in the same lobe as the cancer compared with any other lobe, including the same lung (p<0.0001). Pulmonary scarring was common, and there was a strong association between the geographical location of scarring and primary lung cancer in those with scarring.


Update: the case for patient-specific dosimetry in radionuclide therapy.
In this review of the literature and general practice in the use of radiopharmaceuticals for therapy, an argument is provided to demonstrate that the use of patient-individualized radiation dose assessment should become routine in these forms of therapy, as they are in other uses of radiation in therapy. Individual objections to patient-specific dosimetry will be raised and addressed, using findings presented in the literature. Such approaches are superior to the use of a fixed activity or activity per unit body weight approach in nuclear medicine therapy, which is current practice. It will be demonstrated that standardized and automated methods, with adjustment for patient-specific physical and biokinetic data, are of similar cost and difficulty to those used in other therapeutic modalities. Most importantly, the data show that careful use of patient-individualized dose calculations will produce calculated radiation dose estimates that correlate well with observed effects and that use of a dosimetry-based approach will result in better patient outcomes, improving the quality of medical care for patients and reducing costs for the institutions involved. The conclusion of this analysis is that the time has come for this reasonable paradigm to become routine practice.


Development and Validation of an Autophagy-Related Signature for Head and Neck Squamous Cell Carcinoma.
HNSCC is the sixth most frequent type of malignant carcinoma with a low prognosis rate. In addition, autophagy is important in cancer development and progression. The purpose of this study is to investigate the potential significance of ARGs in the diagnosis and treatment of HNSCC. Expression data and clinical information of HNSCC samples were collected from the TCGA database, and a list of ARGs was obtained from the MSigDB. Then, we used R software to perform differential expression analysis and functional enrichment analysis. Further analysis was also performed to find out the survival-related ARGs in HNSCC, and two prognosis-related ARGs, FADD and NKX2-3, were selected to construct a prognosis prediction model. Moreover, some methods were applied to validate the prognosis prediction model. Finally, we used cell lines and clinical tissue samples of HNSCC to analyze the importance of FADD and NKX2-3. We screened a total of 38 differentially expressed ARGs, and enrichment analysis showed that these genes were mainly involved in autophagy. Then, we selected FADD and NKX2-3 to construct a prognosis model and the risk score calculated by the model was proved to be effective in predicting the survival of HNSCC patients. Additionally, significant differences of the clinicopathological parameters could also be observed in the risk scores and the expression of NKX2-3 and FADD. The expression of FADD and NKX2-3 in cell lines and HNSCC tissue samples also showed the same trends. ARGs may be a potential biomarker for HNSCC prognosis, and targeted therapies for FADD and NKX2-3 are possible to be a new strategy of HNSCC treatment.


Threat vigilance and intrinsic amygdala connectivity.
A well-documented amygdala-dorsomedial prefrontal circuit is theorized to promote attention to threat ("threat vigilance"). Prior research has implicated a relationship between individual differences in trait anxiety/vigilance, engagement of this circuitry, and anxiogenic features of the environment (e.g., through threat-of-shock and movie-watching). In the present study, we predicted that-for those scoring high in self-reported anxiety and a behavioral measure of threat vigilance-this circuitry is chronically engaged, even in the absence of anxiogenic stimuli. Our analyses of resting-state fMRI data (N = 639) did not, however, provide evidence for such a relationship. Nevertheless, in our planned exploratory analyses, we saw a relationship between threat vigilance behavior (but not self-reported anxiety) and intrinsic amygdala-periaqueductal gray connectivity. Here, we suggest this subcortical circuitry may be chronically engaged in hypervigilant individuals, but that amygdala-prefrontal circuitry may only be engaged in response to anxiogenic stimuli.


Experimental and statistical methods to evaluate antibacterial activity of a quaternary pyridinium salt on planktonic, biofilm-forming, and biofilm states.
Robust evaluation and comparison of antimicrobial technologies are critical to improving biofilm prevention and treatment. Herein, a multi-pronged experimental framework and statistical models were applied to determine the effects of quaternary pyridinium salt, 4-acetyl-1-hexadecylpyridin-1-ium iodide (QPS-1), on Streptococcus mutans in the planktonic, biofilm-forming and biofilm cell states. Minimum inhibitory and bactericidal concentrations (MIC and MBC, respectively) were determined via common methods with novel application of statistical approaches combining random effects models and interval censored data to estimate uncertainties. The MICs and MBCs for planktonic and biofilm-forming states ranged from 3.12 to 12.5 μg ml-1, with biofilm values only ≈ 8 times higher. Potent anti-biofilm activity and reactive structural features make QPS-1 a promising antibacterial additive for dental and potentially other biomedical devices. Together, the experimental framework and statistical models provide estimates and uncertainties for effective antimicrobial concentrations in multiple cell states, enabling statistical comparisons and improved characterization of antibacterial agents.


The association between regular cocaine use, with and without tobacco co-use, and adverse cardiovascular and respiratory outcomes.
Understanding the potential impact of cocaine use on health is increasingly important as cocaine use rises in the U.S. This study evaluated the associations of regular cocaine use, with and without tobacco co-use, with cardiovascular and respiratory outcomes. Analysis of a limited dataset obtained through IBM Watson Health Explorys, a platform integrating electronic health record data. Matched controls were defined for: 1) cocaine-using patients (n = 8244; 44 % female); and subgroups of cocaine-using patients: 2) with an encounter diagnosis for tobacco use disorder (TUD; n = 4706); and 3) without a TUD diagnosis (non-TUD; n = 3538). Patients had at least one documented medical evaluation in the MetroHealth System (Cleveland, Ohio). Cocaine-using patients had an encounter diagnosis of cocaine abuse/dependence and/or ≥2 cocaine-positive drug screens. Control patients, with no documented cocaine-use, were matched to the cocaine-using patients on demographics, residential zip code median income, body mass index, and, for the total sample, TUD-status. Outcomes were encounter diagnosis (yes/no) of cerebrovascular accident, heart arrhythmia, myocardial infarction, subarachnoid hemorrhage, asthma, chronic obstructive pulmonary disease (COPD), pneumonia, and all-cause mortality. TUD-patients had the greatest prevalence of cardiovascular and respiratory disease, regardless of cocaine-use indication. In the total sample, TUD, and non-TUD subgroups, regular cocaine use was significantly associated with greater risk for cerebrovascular accident, arrhythmia, myocardial infarction, asthma, COPD, pneumonia and mortality. Cocaine use is associated with significantly greater risk of adverse cardiovascular and respiratory diagnoses and all-cause mortality.


Etching of Cr tips for scanning tunneling microscopy of cleavable oxides.
We report a detailed three-step roadmap for the fabrication and characterization of bulk Cr tips for spin-polarized scanning tunneling microscopy. Our strategy uniquely circumvents the need for ultra-high vacuum preparation of clean surfaces or films. First, we demonstrate the role of ex situ electrochemical etch parameters on Cr tip apex geometry, using scanning electron micrographs of over 70 etched tips. Second, we describe the suitability of the in situ cleaved surface of the layered antiferromagnet La1.4Sr1.6Mn2O7 to evaluate the spin characteristics of the Cr tip, replacing the ultra-high vacuum-prepared test samples that have been used in prior studies. Third, we outline a statistical algorithm that can effectively delineate closely spaced or irregular cleaved step edges, to maximize the accuracy of step height and spin-polarization measurements.


Primary abdominal muscle lymphoma.
Primary skeletal muscle lymphoma accounts for <1% of all lymphomas; a fraction of these arise within the abdominal muscles. Here, we describe the case of an 84-year-old woman who presented with multiple painful abdominal masses that proved to be diffuse large B-cell lymphoma and we discuss the main features of the disease. Clinical differential diagnosis from soft tissue sarcoma can be extremely difficult. Therefore, accurate pathological diagnosis including optimal tissue processing and immunohistochemical staining is vital to ensuring proper treatment.


Accuracy of Fetal Weight Estimation in Women with Diet Controlled Gestational Diabetes.
Purpose: To evaluate whether ultrasound accuracy of estimated fetal weight (EFW) differs in women with diet controlled gestational diabetes mellitus (GDM) compared to nondiabetic pregnant women. Material and Methods: We included 363 patients, 121 patients with diet controlled GDM and 242 patients with a normal oral glucose tolerance test (oGTT). Each case of diet controlled GDM was matched with 2 unaffected controls. All patients were screened/diagnosed for GDM by means of an oGTT. Both groups received ultrasound examination including fetal biometry, using Hadlock's Formula, within 7 days to delivery. After birth, gestational age, birthweight and Apgar scores were collected from each newborn. Results: There was a good correlation between EFW and birth weight (coefficient = 0.747, p < 0.001 by Pearson correlation, even after adjustment for glucose status). Regression analyses, including noGDM/GDM, maternal age, maternal body mass index, birth weight and time interval between ultrasound and delivery revealed that only fetal birth weight significantly influences weight difference between ultrasound EFW and actual birth weight at term. Conclusion: Our data suggests that ultrasound accuracy of EFW using Hadlock's Formula at term does not differ in women with diet controlled GDM compared to women with normal glucose tolerance.


Ex situ hepatectomy and liver autotransplantation for a treating giant solitary fibrous tumor: A case report.
A solitary fibrous tumor (SFT) is a rare mesenchymal tumor. Ex situ hepatectomy and liver autotransplantation are novel methods for the treatment of complicated liver tumors, for example, those involving vascular structures, including the inferior vena cava, which are unresectable by conventional approaches. The present study describes a rare case of a massive hepatic SFT in a 32-year-old female who underwent ex situ hepatectomy and liver autotransplantation to achieve a radical resection. The surgery was without complications. Post-operative histopathological and immunohistochemical examinations revealed an SFT of the liver. The patient was discharged 29 days after the surgery with fully recovered liver function. The routine check-up 3 months after surgery indicated normal liver function and no evidence of recurrence. Additionally, an exhaustive review of available literature was performed to provide a complete overview of the current status of SFTs. In summary, the present study found that ex situ hepatectomy and liver autotransplantation are suitable surgical techniques for treating a giant SFT, as well as other liver neoplasms that are considered unresectable by conventional surgery.


Topological scanning of the P1 plasmid partition site.
The parS site of the P1 plasmid promotes active partition of P1 to daughter cells when the P1 ParA and ParB proteins are provided. The structure of parS was modified by substituting portions of the sequence with synthetic oligonucleotides and testing partition activity of the resulting mutants in an in vivo assay. The boundaries of the site were defined. They enclose a 74 bp region with a central integration host factor (IHF) binding region flanked by two arms containing heptamer and hexamer ParB binding motifs. The IHF binding region was shown to be important for partition activity but could be replaced by sequences containing A tracts that induce static bends in the DNA. The properties of sites with spacer sequences of different lengths inserted at one of five different locations led to the following conclusions. (1) The spacing between the heptamer and hexamer ParB binding motifs in both arms is critical for function. (2) Optimum partition activity requires that the parS site arms are bent toward each other with specific faces of the two helices facing each other. (3) Both arms show torsional rigidity in the active complex. (4) The left arm is laterally inflexible and activity is lost when it is extended unless the right arm is similarly extended. (5) The right arm is laterally flexible so that, when it is extended by an integral number of turns of the helix, it can still align properly with a left arm of wild-type length. The results suggest that right-arm flexibility is promoted by an A + T-rich region that is essential for IHF binding and lies adjacent to the IHF binding consensus motif. Inherent flexibility of this A + T-rich region also appears to account for the residual activity of parS sites in which the IHF binding consensus has been destroyed by multiple point mutations. The results are consistent with a proposed structure in which specific alignment of the parS site arms by an IHF-promoted bend allows them to be linked by bifunctional ParB protein binding. We suggest that such a structure might be involved in the specific pairing and unpairing of daughter plasmids during partition by an isomerization reaction.


Rates of carbon monoxide elimination in males and females.
The purpose of this study was to verify the previously reported shorter half-time of elimination (t½) of carbon monoxide (CO) in females compared to males. Seventeen healthy subjects (nine men) completed three sessions each, on separate days. For each session, subjects were exposed to CO to raise the carboxyhemoglobin percentage (COHb) to ~10%; then breathed in random order, either (a) 100% O2 at poikilocapnia (no CO2 added), or (b) hyperoxia while maintaining normocapnia using sequential gas delivery, or (c) voluntary hyperpnea at~4x the resting minute ventilation. We measured minute ventilation, hemoglobin concentration [Hb] and COHb at 5 min intervals. The half-time of reduction of COHb (t½) was calculated from serial blood samples. The total hemoglobin mass (HbTOT) was calculated from [Hb] and estimated blood volume from a nomogram based on gender, height, and weight. The t½ in the females was consistently shorter than in males in all protocols. This relationship was sustained even after controlling for alveolar ventilation (P < 0.05), with the largest differences in t½ between the genders occurring at low alveolar ventilation rates. However, when t½ was further normalized for HbTOT, there was no significant difference in t½ between genders at alveolar ventilation rates between 4 and 40 L/min (P = 0.24). We conclude that alveolar ventilation and HbTOT are sufficient to account for a major difference in CO clearance between genders under resting (nonexercising) conditions.


Gossypiboma: complete transmural migration of retained surgical sponge causing small bowel obstruction.
The authors report a case of recurrent intestinal obstruction due to complete transmural migration of a retained surgical sponge into the small intestine. A 41-year-old woman presented with recurrent episodes of intestinal obstruction following a previous laparotomy in a private hospital for some gynaecologic procedures. Relaparotomy revealed a mass within the ileum which was resected and, when dissected out, was found to be a completely intraluminal retained surgical sponge. Although rare in daily practice, a retained intraperitoneal foreign body should be remotely considered in patients who present with new abdominal symptoms complex following a history of previous laparatomy.


Refeeding syndrome: multimodal monitoring and clinical manifestation of an internal severe neurotrauma.
Refeeding syndrome (RFS) is a rare, potentially life-threatening, condition seen in malnourished patients starting refeeding. RFS may provoke seizures and acute encephalopathy and can be considered an internal severe neurotrauma in need of specific treatment. The objective was to describe course of disease, treatment and, for the first time, multimodal monitoring output in a comatose patient suffering RFS. After gastric-banding and severe weight loss, the patient initiated self-starving and was transferred to our intensive care unit (ICU) following rapid refeeding. At arrival, seizures, decrease in consciousness (GCS 7) and suspected acute encephalitis was presented. Serum albumin was 8 g/l. Intracranial pressure (ICP), invasive blood pressure and electrocardiography (ECG) were monitored. Pressure reactivity (PRx) and compliance (RAP) were calculated. The patient developed congestive heart failure, anuria and general oedema despite maximal neuro- and general ICU treatment. Global cerebral oedema and hypoperfusion areas with established ischemia were seen. ECG revealed massive cardiac arrhythmia and disturbed autonomic regulation. PRx indicated intact autoregulation (-0.06 ± 0.18, mean ± SD) and relatively normal compliance (RAP = 0.23 ± 0.13). After 15 days the clinical state was improved, and the patient returned to the primary hospital. RFS was associated with serious deviations in homeostasis, high ICP levels, ECG abnormalities, kidney and lung affections. It is of utmost importance to recognize this rare syndrome and to treat appropriately. Despite the severe clinical state, cerebral autoregulation and compensatory reserve were generally normal, questioning the applicability of indirect measurements such as PRx and RAP during neuro-intensive care treatment of RFS patients with cerebral engagement.


Prospective, Randomized, Multicenter, Controlled Trial (TRIATHRON 1) on a New Antithrombogenic Hydrophilic Dialysis Membrane.
Hemodialysis treatment requires anticoagulation to prevent thrombosis of the dialyzer. The Hydrolink® (NV series; Toray) has been designed to reduce thrombotic complications by increasing membrane hydrophilic properties. Previous studies have confirmed reduced platelet activation, improved removal of β2-microglobulin and excellent small-solute removal. We designed a prospective, multi-centered, randomized clinical study to compare the antithrombogenic effects (platelet count) of NV dialyzers versus conventional treatment. To compare the possibility of performing heparin-free dialysis, we carried out progressive heparin reduction tests. Patients with an average platelet count lower than 170,000 cells/mm3 using standard high flux membranes in the 6 months prior to the study were enrolled and randomized. Patients were either dialyzed for 6 months without changing the previous membrane (control group) or treated with the Hydrolink® membrane (NV group). After the third week, the heparin reduction test was conducted for 5 weeks in order to assess the minimum amount of anticoagulant needed to safely perform a 4-hour dialysis treatment. Performance and safety were evaluated measuring platelet count and activation, middle-molecule removal rate and nutritional status. We found no significant difference in platelet count, platelet activation factors β-thromboglobulin and platelet factor 4 (PF-4), between the groups. More patients in the study group reached heparin-free dialysis without clotting events during the heparin reduction test. The NV dialyzers displayed anti-thrombogenic effects as compared to conventional dialyzers. The NV dialyzer series is safe with no adverse events reported. Further studies are required to understand the mechanisms of anti-thrombogenic effects.


In situ chemical reduction of Cr(VI) in groundwater using a combination of ferrous sulfate and sodium dithionite: a field investigation.
A field study was conducted to evaluate the performance of a ferrous iron based in situ redox zone for the treatment of a dissolved phase Cr(VI) plume at a former industrial site. The ferrous iron based in situ redox zone was created by injecting a blend of 0.2 M ferrous sulfate and 0.2 M sodium dithionite into the path of a dissolved Cr(VI) plume within a shallow medium to fine sand unconfined aquifer formation. Monitoring data collected over a period of 1020 days after more than 100 m of linear groundwater flow through the treatment zone indicated sustained treatment of dissolved phase Cr(VI) from initial concentrations between 4 and 8 mg/L to less than 0.015 mg/L. Sustained treatment is assumed to be primarily due to the reduction of Cr(VI) to Cr(III) by ferrous iron adsorbed to, precipitated on, and/or incorporated into aquifer iron (hydr)oxide solid surfaces within the treatment zone. Precipitated phases likely include FeCO3 and FeS based on saturation index considerations and SEM/EDS analysis. The detection of solid phase sulfites and thiosulfates in aquifer sediments collected from the treatment zone more than 2 years following injection suggests dithionite decomposition products may also play a significant role in the long-term treatment of the dissolved phase Cr(VI).


Leucocyte depletion in a drowning victim during rewarming with extracorporeal circulation may limit pulmonary oedema.
We report two drowning victims with hypothermic circulatory arrest who were resuscitated with the use of extracorporeal circulation (ECC). The first patient developed severe post-bypass pulmonary oedema and inspired us to use a leucocyte-depletion filter in the second patient to attenuate leucocyte-mediated pulmonary reperfusion injury. In the first patient, a standard extracorporeal circuit was used. In the second patient, systemic leucocyte depletion was applied using leucocyte-depletion filters (Pall RS 1, Pall, Portsmouth, UK), in the venous side of the extracorporeal circuit. Circulating leucocyte counts were measured and arterial blood gas analysis and chest X-rays were performed. Both patients showed a decrease of the circulating leucocyte counts during rewarming and had nearly similar leucocyte counts on arrival at the intensive care unit (ICU). The first patient developed severe pulmonary oedema, with poor arterial blood gases, whereas the second patient, who had leucocyte-depletion by filtration, did not develop severe pulmonary oedema, and had good arterial blood gases. Profound leucocyte-depletion by means of filtration may have contributed to limit leucocyte-mediated pulmonary reperfusion injury.


Acute intermittent porphyria complicated by pregnancy.
The case of a woman with acute intermittent porphyria complicated by two pregnancies is described. Both pregnancies gave an exacerbation of the disease. Premature delivery were necessary for both children due to intrauterine growth retardation. The first child died from respiratory distress syndrome, but the second child was healthy apart from transient abstinence symptoms due to pethidine given to the mother during pregnancy. The effect of pregnancy on acute intermittent porphyria is discussed.


Phytochemical and therapeutic evaluation of leaf and in vitro derived callus and shoot of Solanum trilobatum.
This study focuses on the phytochemical properties and the anti-hepatocarcinogenic effects of the leaf and in vitro-derived callus and shoot extracts of Solanum trilobatum. In the leaf, callus and shoot, the presence of sugar, proteins, alkaloids, flavonoids, saponins, tananins, cardiacglycoside, terpenoid and lipids was established by preliminary phytochemical screening. Surface-sterilized explants (0.5-1.0 cm) were placed on the MS basal medium supplemented with different concentrations of 2,4-dichlorophenoxyacetic acid (0.45, 2.26, 4.52, 11.31 and 12.56 μ M), naphthylacetic acid (NAA; 0.54, 1.34, 2.69, 5.37, 13.43 and 26.85 μM) and 6-benzylaminopurine (BA; 0.44, 1.11, 2.22, 4.44, 8.88 and 13.32 μM) for callus induction. Explants from node and callus culture were inoculated on the MS basal medium supplemented with varying concentrations of BA (0.44-22.20 μM) and NAA (0.54-10.74 μM) for shoot multiplication. Rats were divided into five groups and administered with diethyl nitrosamine (DEN) and DEN (200mg/kg bwt) intraperitoneally along with methanol leaf and in vitro-derived callus and shoot extracts (250 mg/kg bwt) orally for 3 months. A significant deviation (P<0.05) in marker enzymes such as alanine transaminase, aspartate transaminase, lactate dehydrogenase and total bilirubin was found in rats administered with DEN. The liver tissue was used for the analysis of glutathione reductase, lipid peroxidation, glutathione peroxidase, glutathione S-transferase, superoxide dismutase and catalase. DEN administration caused a significant elevation in serum enzymes and total bilirubin. Moreover, antioxidant enzymes were drastically inhibited with significant reduction in glutathione and increased lipid per oxidation. Increased glutathione level and reduced lipid peroxidation were also evident in S. trilobatum-treated rats. However, crude S. trilobatum and in vitro-derived callus and shoot extracts offered better protection against free radical toxicity induced by DEN.


Symmetry reduction for deep reinforcement learning active control of chaotic spatiotemporal dynamics.
Deep reinforcement learning (RL) is a data-driven, model-free method capable of discovering complex control strategies for macroscopic objectives in high-dimensional systems, making its application toward flow control promising. Many systems of flow control interest possess symmetries that, when neglected, can significantly inhibit the learning and performance of a naive deep RL approach. Using a test-bed consisting of the Kuramoto-Sivashinsky equation (KSE), equally spaced actuators, and a goal of minimizing dissipation and power cost, we demonstrate that by moving the deep RL problem to a symmetry-reduced space, we can alleviate limitations inherent in the naive application of deep RL. We demonstrate that symmetry-reduced deep RL yields improved data efficiency as well as improved control policy efficacy compared to policies found by naive deep RL. Interestingly, the policy learned by the symmetry aware control agent drives the system toward an equilibrium state of the forced KSE that is connected by continuation to an equilibrium of the unforced KSE, despite having been given no explicit information regarding its existence. That is, to achieve its goal, the RL algorithm discovers and stabilizes an equilibrium state of the system. Finally, we demonstrate that the symmetry-reduced control policy is robust to observation and actuation signal noise, as well as to system parameters it has not observed before.


Electron microscopic radioautographic study of the localization of an anti-allergic agent, Tranilast, in rat mast cells.
We have previously reported that Tranilast, an anti-allergic agent, was rapidly taken into the cytoplasm of rat mast cells in vitro by means of light microscopic radioautography. The present study was performed at the electron microscopic level to elucidate the fine localization of this agent in the mast cells. The results revealed that the number of radioautographic silver grains in the cells increased by the incubation with 3H-labelled Tranilast for 0 to 60 min. and that many silver grains were localized on the specific granules, especially on the perigranular membranes. These results suggest that the mode of inhibitory action of mast cell degranulation by Tranilast is related to the specific localization of this agent on the perigranular membranes.


Basal cell carcinoma of the prostate: A case report and review of the literature.
Basal cell carcinoma (BCC) of the prostate is a rare tumor exhibiting various morphological characteristics, and its progression varies from an indolent to an aggressive type, with local recurrence or distant metastasis. We herein report the case of a patient who was diagnosed with early-stage BCC of the prostate and treated by surgery. A 68 year-old-man visited our hospital for a follow-up for bladder cancer. In August 2017, his serum prostate-specific-antigen (PSA) level was measured to be 5.61 ng/ml and prostate biopsy was performed. Histological examination revealed BCC of the prostate, with immunostaining examination of tumor cells showing positive results for p63 but negative results for PSA. Imaging examination showed no metastasis. Retropubic radical prostatectomy with extended lymph node dissection was performed. Pathological examination of the surgical specimen revealed coexistence of a predominant basaloid component and an adenoid cystic-like tumor with cribriform appearance. There was no extracapsular infiltration or lymph node metastasis. The patient remained alive and recurrence-free after 1 year of follow-up.


Global estimates of rehabilitation needs and disease burden in tracheal, bronchus, and lung cancer from 1990 to 2019 and projections to 2045 based on the global burden of disease study 2019.
The global cancer burden is substantial and spiraling. Although rehabilitation specialists could offer assistance, oncologic rehabilitation is still underutilized and not a routine part of clinical oncology guidelines worldwide. Global investigations of disease prevalence and years lived with disability (YLDs) for tracheal, bronchus, and lung (TBL) cancer are valuable for facilitating clinical practice improvement and health resource management. The objective of this study is to report the global estimates of rehabilitation needs and disease burden of TBL cancers from 1990 to 2019 and provide predictions for 2045. To estimate the need for rehabilitation, the data used from the Global Burden of Disease Study 2019 to calculate the prevalence, YLDs, and the attributable risk factors of TBL cancer. The Bayesian age-period-cohort model and Auto-Regressive Integrated Moving Average model were established to forecast the future health burden. All analyses were done at the global level and then some in the aggregation with the seven World Bank regions. All the data were analyzed by R software (x64 version 4.2.1) and Microsoft Excel (version 2019). Globally in 2019, 3,212,307 cases of TBL cancer (95% UI 2,937,037-3,488,346) could have benefitted from rehabilitation, contributing to 544,215 (95% UI 396,134-700,099) YLDs. Over the past 30 years, the age-standardized rate (ASR) of prevalence (EAPC = 0.51) and YLDs (EAPC = 0.03) increased. Throughout this period, the global prevalence and YLDs counts were greater in males than females. The ASR of prevalence and YLDs are projected to show a slight downward trend by 2045 on the global scale, the overall prevalence and YLDs due to TBL cancer are likely to increase further, but all indicators show a growing trend in females. TBL cancer remains one of the major public health issues globally. According to the forecasted results, the burden of YLDs due to TBL cancer will continue to rise, and the increment is higher in females than males. A rising number of patients worldwide will benefit from rehabilitation services in the future to achieve precise control and management throughout the TBL cancer patient lifecycle.


Prolactin fluctuation over the course of a day during treatments with three atypical antipsychotics in schizophrenic patients.
Hyperprolactinemia is a frequent consequence of treatment with some antipsychotic agents. Although prolactin secretion varies over the course of a day and during psychological circumstances, there is little information in the literature regarding the time dependence of the prolactin response to antipsychotics. We evaluated prolactin levels in schizophrenic patients receiving risperidone (3 mg twice daily), olanzapine (10 mg twice daily), or perospirone (16 mg twice daily) for at least 4 weeks. The subjects were compared to matched healthy controls. Plasma sample collection for quantification of drug and prolactin levels was conducted before and 2, 4, 6, 8, and 12 h after the morning dosing. Prolactin concentrations before dosing during risperidone treatment were significantly higher than during treatment with olanzapine and perospirone in females. The daily fluctuation of prolactin concentration after perospirone treatment was larger than that observed after risperidone and olanzapine treatments. Areas under the plasma concentration-time curves was greatest in subjects treated with risperidone, followed by perospirone and finally by olanzapine. These findings suggest that daily fluctuations in prolactin concentration after perospirone treatment are larger than following treatment with risperidone and olanzapine. The plasma concentration of prolactin during perospirone treatment therefore depends on the time of sampling.