Diagnostic and prognostic impact of fluorine-18-fluorodeoxyglucose PET/CT in preoperative and postoperative setting of breast cancer patients.
The aim of this study was to assess the diagnostic and prognostic value of fluorine-18-fluorodeoxyglucose (F-FDG) PET/CT in patients with breast cancer (BC) in the preoperative and the postoperative setting. Between 2011 and 2015, we prospectively enrolled 275 patients (mean age: 53 years) with BC (stage I-III; triple-negative or HER2-positive cancer). One-hundred and forty-nine (54.2%) patients underwent F-FDG PET/CT before neoadjuvant therapy and 126 (45.8%) after surgery and before any additional adjuvant therapy. The patients were followed for a median period of 44 (2-57) months. The different effects of PET/CT on the presetting and postsetting phase form a therapeutic and prognostic point of view were assessed by χ, by Kaplan-Meier, and Cox-regression analyses. In the preoperative setting, PET/CT provided additional diagnostic information in 42/149 (28%) patients. In particular, 17/70 (24%) patients at stage III were converted into stage IV and 4/68 (6%) at stage II were upstaged to IV. In the postoperative setting, PET/CT upstaged the disease in both stage IIIC and stage IV in 14/126 (11%) cases. At the end of follow-up, 28/271 (10%) patients died from BC and 40 (15%) had a recurrence of disease. On Kaplan-Meier analysis, patients with a positive PET/CT other than the primary tumor site showed both a worse overall survival and a worse disease-free survival compared with their counterpart (76 vs. 92%; P=0.063 and 65 vs. 100%; P<0.001). Conversely, in the postoperative setting, no differences in overall survival and disease-free survival were found between patients with positive and negative PET/CT findings (both P>0.05). On multivariate Cox-regression analysis, a positive PET/CT was a significant predictive factor of a poor prognosis in the preoperative setting. The significance was lost in the postoperative setting. In the preoperative setting, PET/CT can provide additional diagnostic and prognostic information. Conversely, in the postoperative setting, PET/CT adds diagnostic information, but does not provide any adjunctive prognostic assessment.


Alpha and beta neural oscillations differentially reflect age-related differences in bilateral coordination.
Bilateral in-phase (IP) and anti-phase (AP) movements represent two fundamental modes of bilateral coordination that are essential for daily living. Although previous studies have shown that aging is behaviorally associated with decline in bilateral coordination, especially in AP movements, the underlying neural mechanisms remain unclear. Here, we use kinematic measurements and electroencephalography to compare motor performance of young and older adults executing bilateral IP and AP hand movements. On the behavioral level, inter-limb synchronization was reduced during AP movements compared to IP and this reduction was stronger in the older adults. On the neural level, we found interactions between group and condition for task-related power change in different frequency bands. The interaction was driven by smaller alpha power decreases over the non-dominant cortical motor area in young adults during IP movements and larger beta power decreases over the midline region in older adults during AP movements. In addition, the decrease in inter-limb synchronization during AP movements was predicted by stronger directional connectivity in the beta-band: an effect more pronounced in older adults. Our results therefore show that age-related differences in the two bilateral coordination modes are reflected on the neural level by differences in alpha and beta oscillatory power as well as interhemispheric directional connectivity.


The impact of a minimum unit price on wholesale alcohol supply trends in the Northern Territory, Australia.
The Northern Territory (NT) Government introduced a minimum unit price (MUP) of $1.30 per standard drink (10g pure alcohol) explicitly aimed at reducing the consumption of cheap wine products from October 2018. We aimed to assess the impact of the NT MUP on estimates of beverage-specific population-adjusted alcohol consumption using wholesale alcohol supply data. Interrupted time series analyses were conducted to examine MUP effects on trends in estimated per capita alcohol consumption (PCAC) for cask wine, total wine and total alcohol, across the NT and in the Darwin/Palmerston region. Significant step decreases were found for cask wine and total wine PCAC in Darwin/Palmerston and across the Northern Territory. PCAC of cask wine decreased by 50.6% in the NT, and by 48.8% in Darwin/Palmerston compared to the prior year. PCAC for other beverages (e.g. beer) were largely unaffected by MUP. Overall, PCAC across the Territory declined, but not in Darwin/Palmerston. With minimal implementation costs, the Northern Territory Government's MUP policy successfully targeted and reduced cask wine and total wine consumption. Cask wine, in particular, almost halved in Darwin/Palmerston where the impact of the MUP was able to be determined and considering other interventions. Implications for public health: Implementation of a minimum unit price for retail alcohol sales is a cost-effective way to reduce the consumption of high alcohol content and high-risk products, such as cheap cask wine.


Environmental Exposure to Pesticides and Breast Cancer in a Region of Intensive Agribusiness Activity in Brazil: A Case-Control Study.
Background: Breast cancer is a serious public health problem and is the second most prevalent cancer type in the world. The purpose of this article is to evaluate the association between pesticide use and breast cancer in a region of intense agribusiness activity in the state of Mato Grosso, Brazil. Methods: A case-control study was conducted on women living in the city of Rondonópolis, in the south of Mato Grosso state. There were 85 cases of women with confirmed breast cancer and 266 controls who were randomly selected from primary health care users. Bivariate and stratified analyses were performed. Multiple logistic regression was then performed, keeping in the final model the factors with a significance level lower than or equal to 0.05 or considered important according to apriori biological criteria. Results: In the final model, living near cropland with pesticides (OR: 2.37; CI: 95% 1.78-3.16) and women aged over 50 years who experienced early menarche (OR: 2.08; CI: 95% 1.06-4.12) had a higher risk of developing breast cancer compared to control subjects. Conclusion: This study highlights the importance of exposure to pesticides as an environmental risk factor for the development of breast cancer among women.


Cigarette smoking and benign breast disease.
The association between cigarette smoking and the occurrence of benign breast disease was assessed in a hospital-based case-control study conducted in Connecticut during 1979-81. Current smokers, but not former smokers, were at reduced risk for all benign breast diseases. The odds ratios associated with current smoking were 0.7 (95% confidence intervals = 0.6, 0.9) for fibrocystic breast disease, 0.6 (95% confidence intervals = 0.5, 0.9) for fibroadenoma, 0.6 (95% confidence intervals = 0.4, 1.0) for fibrocystic breast disease concomitant with fibroadenoma, and 0.6 (95% confidence intervals = 0.5, 0.9) for other benign breast disease. Adjustments for potentially confounding variables, including indices of medical care utilisation, affected these odds ratios only slightly. There was no convincing evidence of an association, either negative or positive, between current cigarette smoking and the degree of epithelial atypia of the fibrocystic lesions. However, the negative association between fibrocystic disease and current cigarette smoking was strongest for atypical lobular hyperplasia, which in turn has been associated with a particularly elevated risk of subsequent breast cancer.


Notes on recombination and reassortment in multipartite/segmented viruses.
Besides evolving through nucleotide substitution, viruses frequently also evolve by genetic recombination which can occur when related viral variants co-infect the same cells. Viruses with segmented or multipartite genomes can additionally evolve via the reassortment of genomic components. Various computational techniques are now available for identifying and characterizing recombination and reassortment. While these techniques have revealed both that all well studied segmented and multipartite virus species show some capacity for reassortment, and that recombination is common in many multipartite species, they have indicated that recombination is either rare or does not occur in species with segmented genomes. Reassortment and recombination can make it very difficult to study segmented/multipartite viruses using metagenomics-based approaches. Notable challenges include, both the accurate identification and assignment of genomic components to individual genomes, and the differentiation between natural 'real' recombination events and artifactual 'fake' recombination events arising from the inaccurate de novo assembly of genome component sequences determined using short read sequencing.


[Association of schizophrenia and Recklinghausen's disease].
Two cases of associated Recklinghausen's disease and different forms of schizophrenia (sluggish psychopathlike and shift-like paranoid) are described. Of special interest was the fact that such association was observed in two brothers. Based on the clinical material suggested, the conclusion was made about the modifying influence of the organism process in Recklinghausen's disease (brain gliosis) on the schizophrenic process, thereby creating certain difficulties in the diagnosis. It is also assumed that the age of the onset of Recklinghausen's disease may determine the clinical picture of the mental pathology.


Behavioral differences between urban feeding groups of neutered and sexually intact free-roaming cats following a trap-neuter-return procedure.
To examine behavioral differences during a 1-year observational period between urban feeding groups of neutered and sexually intact free-roaming cats following a trap-neuter-return procedure. Natural-setting trial. Animals-Free-roaming cats (n = 184) living in 4 feeding groups in an urban region of Israel. Trap-neuter-return procedures were applied to 2 cat feeding groups (A and B). Their social and feeding behaviors and frequency of appearance at feeding time were compared with those of 2 unneutered cat groups (C and D). Behavioral data were obtained from weekly observations before and during feeding over a 1-year period. Results-A lower rate of agonistic interactions was observed in the neutered groups than in the unneutered groups. Sexually intact male cats participated in more agonistic male-male encounters than did neutered male cats. Of 199 such encounters in the feeding groups, only 1 occurred between 2 neutered males. Neutered cats in group A appeared earlier and had higher frequencies of feeding and appearance at the feeding site, compared with unneutered cats. Less aggression was observed in the neutered groups, specifically, fewer agonistic neutered-neutered male encounters occurred. This reduced agonistic behavior of neutered males resulted in reduced fighting and vocalizations, potentially leading to fewer injuries and reduced transmission of fight-related infectious diseases and reduced noise disturbance from a human perspective. Regarding food delivery, the feeding groups were time-and-place dependent, exhibiting context-related social interactions. When competing for food resources, as neutered cats time their arrival in accordance with food delivery, they thereby gain access to the choicest items.


Venezuelan equine encephalitis replicon particles can induce rapid protection against foot-and-mouth disease virus.
We have previously shown that delivery of the porcine type I interferon gene (poIFN-α/β) with a replication-defective human adenovirus vector (adenovirus 5 [Ad5]) can sterilely protect swine challenged with foot-and-mouth disease virus (FMDV) 1 day later. However, the need of relatively high doses of Ad5 limits the applicability of such a control strategy in the livestock industry. Venezuelan equine encephalitis virus (VEE) empty replicon particles (VRPs) can induce rapid protection of mice against either homologous or, in some cases, heterologous virus challenge. As an alternative approach to induce rapid protection against FMDV, we have examined the ability of VRPs containing either the gene for green fluorescent protein (VRP-GFP) or poIFN-α (VRP-poIFN-α) to block FMDV replication in vitro and in vivo. Pretreatment of swine or bovine cell lines with either VRP significantly inhibited subsequent infection with FMDV as early as 6 h after treatment and for at least 120 h posttreatment. Furthermore, mice pretreated with either 10(7) or 10(8) infectious units of VRP-GFP and challenged with a lethal dose of FMDV 24 h later were protected from death. Protection was induced as early as 6 h after treatment and lasted for at least 48 h and correlated with induction of an antiviral response and production of IFN-α. By 6 h after treatment several genes were upregulated, and the number of genes and the level of induction increased at 24 h. Finally, we demonstrated that the chemokine IP-10, which is induced by IFN-α and VRP-GFP, is directly involved in protection against FMDV.


High-Performance All-Inorganic Solid-State Sodium-Sulfur Battery.
All-inorganic solid-state sodium-sulfur batteries (ASSBs) are promising technology for stationary energy storage due to their high safety, high energy, and abundant resources of both sodium and sulfur. However, current ASSB shows poor cycling and rate performances mainly due to the huge electrode/electrolyte interfacial resistance arising from the insufficient triple-phase contact among sulfur active material, ionic conductive solid electrolyte, and electronic conductive carbon. Herein, we report an innovative approach to address the interfacial problem using a Na3PS4-Na2S-C (carbon) nanocomposite as the cathode for ASSBs. Highly ionic conductive Na3PS4 contained in the nanocomposite can function as both solid electrolyte and active material (catholyte) after mixing with electronic conductive carbon, leading to an intrinsic superior electrode/electrolyte interfacial contact because only a two-phase contact is required for the charge transfer reaction. Introducing nanosized Na2S into the nanocomposite cathode can effectively improve the capacity. The homogeneous distribution of nanosized Na2S, Na3PS4, and carbon in the nanocomposite cathode could ensure a high mixed (ionic and electronic) conductivity and a sufficient interfacial contact. The Na3PS4-nanosized Na2S-carbon nanocomposite cathode delivered a high initial discharge capacity of 869.2 mAh g-1 at 50 mA g-1 with great cycling and rate capabilities at 60 °C, representing the best performance of ASSBs reported to date and therefore constituting a significant step toward high-performance ASSBs for practical applications.


[Postoperative cardiac morbidity/mortality in high-risk elderly patients undergoing non-cardiac surgery].
To analyze cardiac morbidity and mortality after major noncardiac surgery in high-risk elderly patients. Retrospective study of patients 65 years old or older in the postoperative intensive care unit between January 1990 and September 1996, after major noncardiac surgery, with histories of known ischemic heart disease (IHD group) or with two or more coronary risk factors (CRF group). We analyzed age, number of risk factors, type of ischemic heart disease, type and nature of surgery and cardiac morbidity or mortality. Five hundred twenty-nine patients were studied. Mean age was 72.1 +/- 5.1 years. The CRF group contained 366 patients (69.1%); the IHD group contained 163 (30.2%) patients with angina or histories of myocardial infarction. Rates of morbidity in the two groups were 10.1% and 25.8%, respectively (p < 0.001); the cardiac death rates were 2.18% and 5.5%, respectively (p = 0.08). No effect of number of coronary risk factors, type of ischemic heart disease, or type of surgery was found. Emergency surgery was associated with greater morbidity (p < or = 0.0011 and p < 0.001, respectively) and mortality (p < 0.001 in both groups). Age over 75 years was related to increased rates of morbidity (p = 0.003) and mortality (p = 0.031). In our practice elderly patients with known ischemic heart disease undergoing major noncardiac surgery suffer more postoperative cardiac complications than do those who only have coronary risk factors. Mortality, however, is similar. The only factors associated with increased morbidity and mortality are emergency surgery and age over 75 years.


Comparision between bed side testing of blood glucose by glucometer vs centralized testing in a tertiary care hospital.
To determine the accuracy, turnaround time and cost effectiveness of bedside monitoring of blood glucose levels by non-laboratory health care workers and centralized testing of blood glucose by automated analyzer in a tertiary care hospital. The study was conducted in Section of Chemical Pathology, Department of Pathology and Microbiology and Section of Endocrinology Department of Medicine, Aga Khan University and Hospital Karachi, from April 2005 to March 2006. One hundred and ten patients were included in the study. The blood glucose levels were analyzed on glucometer (Precision Abbott) by finger stick, using Biosensor Technology. At the same time venous blood was obtained to analyze glucose in clinical laboratory on automated analyzer (SYNCHRON CX7) by glucose oxidase method. We observed good correlation between bed side glucometer and laboratory automated analyzer for glucose values between 3.3 mmol/L (60 mg/dl) and 16.7 (300 mg/dl). A significant difference was observed for glucose values less than 3.3 mmol/L (p = 0.002) and glucose values more than 16.67 mmol/l (p = 0.049). Mean Turnaround time for glucometer and automated analyzer were 0.08 hours and 2.49 hours respectively. The cost of glucose testing with glucometer was 48.8% lower than centralized lab based testing. Bedside glucometer testing, though less expensive does not have good accuracy in acutely ill patient with either very high or very low blood glucose levels.


Accounting for the association of family conflict and heavy alcohol use among adolescent girls: the role of depressed mood.
Heavy alcohol use increases dramatically at age 14, and there is emerging cross-sectional evidence that when girls experience family conflict at younger ages (11-13 years) the risk of alcohol use and misuse is high. This study evaluated the role of family conflict and subsequent depressed mood in predicting heavy alcohol use among adolescent girls. This was a three-wave longitudinal study with annual assessments (modal ages 12, 13, and 14 years). The participants (N = 886, 57% female) were from 12 metropolitan schools in Victoria, Australia, and participants completed questionnaires during school class time. The key measures were based on the Communities That Care Youth Survey and included family conflict (Wave 1), depressed mood (Wave 2), and heavy alcohol use (Wave 3). Control variables included school commitment, number of peers who consumed alcohol, whether parents were living together, and ethnic background. With all controls in the model, depressed mood at Wave 2 was predicted by family conflict at Wave 1. The interaction of family conflict with gender was significant, with girls showing a stronger association of family conflict and depressed mood. Depressed mood at Wave 2 predicted heavy alcohol use at Wave 3. Girls may be especially vulnerable to family conflict, and subsequent depressed mood increases the risk of heavy alcohol use. The results support the need for gender-sensitive family-oriented prevention programs delivered in late childhood and early adolescence.


Isolation and functional analysis of normal canine blood monocytes and resident alveolar macrophages.
The percentage of mononuclear phagocytes bearing the Fc receptor for immunoglobulin G, the percentage of cells phagocytic for Candida albicans and latex particles, and the phagocytic index for blood monocytes and alveolar macrophages from healthy dogs are reported. Blood monocytes were concentrated by density-gradient centrifugation, whereas alveolar macrophages were obtained in high yield by bronchoalveolar lavage. Adherent populations of those cells were used for functional assays after repeated washing to remove nonadherent cells. A greater percentage of adherent alveolar macrophages than adherent blood monocytes showed evidence of the Fc receptor for immunoglobulin G. Similarly, adherent alveolar macrophages showed significantly greater phagocytic ability, as measured by percent phagocytic cells and phagocytic index, using C albicans and latex particles, than did adherent canine blood monocytes.


Leucine regulates translation initiation in rat skeletal muscle via enhanced eIF4G phosphorylation.
The BCAA, leucine, stimulates protein synthesis in skeletal muscle in part through enhanced initiation of mRNA translation. However, understanding how leucine regulates protein synthesis remains elusive. The intent of the present investigation was to examine the effect of leucine, independent of other regulatory agents, on key events in translation initiation in skeletal muscle and to elucidate the extent to which signaling through the mammalian target of rapamycin (mTOR) accounts for the effect of the amino acid on protein synthesis. Hindlimb preparations from postabsorptive rats were perfused with medium containing food-deprived (1X) or superphysiologic (10X) concentrations of leucine with all other amino acids at 1X concentration. Protein synthesis was significantly greater in both gastrocnemius and soleus perfused with 10X compared with 1X leucine. The stimulatory effects of leucine on protein synthesis were unaffected by a specific inhibitor of PI3-kinase (LY 294002). Moreover, signaling through mTOR, as monitored by the phosphorylation status of eukaryotic initiation factor (eIF)4E binding protein-1 (4E-BP1) or the 70-kDa ribosomal protein S6 kinase (S6K1), was not further enhanced by 10X compared with 1X leucine. However, binding of eIF4E to eIF4G and eIF4G(Ser-1108) phosphorylation in the eIF4E immunoprecipitate were enhanced as was eIF4G(Ser-1108) phosphorylation in the total tissue extract after perfusion with medium containing 10X leucine. Collectively, these observations illustrate an experimental model whereby leucine in the absence of other regulatory agents stimulates eIF4E. eIF4G assembly and protein synthesis directly in skeletal muscle, possibly by augmenting phosphorylation of eIF4G through a signaling pathway independent of mTOR.


Primary germ cell tumours of the mediastinum: A review with emphasis on diagnostic challenges.
This article will review current aspects of the histopathological, immunohistochemical and molecular analysis of primary mediastinal germ cell tumours (PMGCTs) as well as their aetiological, epidemiological, clinical and therapeutic features. PMGCTs represent an important differential diagnosis in the spectrum of mediastinal tumours, and their diagnosis is usually made on small tissue samples from core needle biopsies in combination with diagnostic imaging and serum tumour markers. As in lymphomas, a small biopsy is often the only viable tumour sample available from these patients, as they receive chemotherapy prior to eventual surgical resection. Pathologists therefore need to apply an efficient combination of immunohistochemical markers to confirm the diagnosis of a PMGCT and to exclude morphological mimics.


The role of sentence position, allomorph, and morpheme type on accurate use of s-related morphemes by children who are hard of hearing.
Production accuracy of s-related morphemes was examined in 3-year-olds with mild-to-severe hearing loss, focusing on perceptibility, articulation, and input frequency. Morphemes with /s/, /z/, and /ɪz/ as allomorphs (plural, possessive, third-person singular -s, and auxiliary and copula "is") were analyzed from language samples gathered from 51 children (ages: 2;10 [years;months] to 3;8) who are hard of hearing (HH), all of whom used amplification. Articulation was assessed via the Goldman-Fristoe Test of Articulation-Second Edition, and monomorphemic word final /s/ and /z/ production. Hearing was measured via better ear pure tone average, unaided Speech Intelligibility Index, and aided sensation level of speech at 4 kHz. Unlike results reported for children with normal hearing, the group of children who are HH correctly produced the /ɪz/ allomorph more than /s/ and /z/ allomorphs. Relative accuracy levels for morphemes and sentence positions paralleled those of children with normal hearing. The 4-kHz sensation level scores (but not the better ear pure tone average or Speech Intelligibility Index), the Goldman-Fristoe Test of Articulation-Second Edition, and word final s/z use all predicted accuracy. Both better hearing and higher articulation scores are associated with improved morpheme production, and better aided audibility in the high frequencies and word final production of s/z are particularly critical for morpheme acquisition in children who are HH.


Laccase-Conjugated Nanostructured ZnFe2O4/rGO-Modified Electrode-Based Interfaces for Electrochemical Impedance Monitoring of Adrenaline: A Promising Biosensor for Management of Neurodegenerative Disorders.
A propitious biosensor for adrenaline (AD) detection in bovine serum albumin (BSA) real samples, which can be used for diagnosis and treatment of neurodegenerative disorders, is reported here. The biosensor consists of a La/ZF/rGO/ITO bioelectrode, which is fabricated by electrophoretic deposition of zinc ferrite/reduced graphene oxide (ZF/rGO) nanohybrid followed by drop casting of laccase (La) enzymes. The material characterization and electrochemical studies revealed that the ZF/rGO nanohybrid enhanced the electroactive surface and facilitated direct electron transfer between the electrode and electrolyte interface, resulting in enhanced electrocatalytic performance. The cyclic voltammetry and electrochemical impedance spectroscopy results asserted that the ZF/rGO nanohybrid decreased the charge-transfer resistance (Rct) and increased the surface adsorption, leading to a high diffusion coefficient (D) of 0.192 cm2/s. The biosensor exhibited a high sensitivity of 0.71 Ω/μM cm2, a good linear range (0.1 to 140 μM with R2 = 0.98), and a low limit of detection (LOD) is 12.5 μM, demonstrating the synergic effect of ZF and rGO in the La/ZF/rGO/ITO bioelectrode with AD. The biosensor also exhibited high selectivity and stability (55 days) in the presence of interfering substances and in BSA samples, with a recovery percentage close to 100 ± 5% RSD, indicating its potential biosensing applications for real-world applications in disease diagnostics, monitoring, and treatment.


Afghan Refugee Explanatory Models of Depression: Exploring Core Cultural Beliefs and Gender Variations.
Relatively little empirical attention has been paid to understanding how refugees conceptualize depression and how this concept varies between genders. The purpose of this study was to explore beliefs about depression among Afghans residing in San Diego County, California, using cultural consensus analysis. Using the prescribed mixed-method approach, we employed results from in-depth interviews to develop a culturally meaningful questionnaire about depression. Consensus analysis of responses to questionnaire items from 93 Afghans (50 men, 43 women) indicates shared beliefs that associates depression causality with mild traumatic experiences and post-resettlement stressors, symptomatology to include culturally salient idioms of distress, and treatment selections ranging from lay techniques to professional care. Divergence between genders occurred most in the symptoms subdomain, with women associating depression with more somatic items. This study contributes to understanding the etiology of and cultural responses to depression among this population, which is critical to improving culturally sensitive intervention for Afghan refugees.


Immunosuppressive Drugs and COVID-19: A Review.
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is currently unknown whether immunosuppressive drugs are advantageous or detrimental in patients with COVID-19. Immunosuppressive drugs could be harmful in the initial phase of COVID-19. In this phase, the host immune response is necessary to inhibit viral replication. However, immunosuppressive drugs might have a beneficial effect in the later, more severe phase of COVID-19. In this phase, an overshoot of the host immune response (the "cytokine storm") can cause ARDS, multiorgan failure and mortality. To summarize the available evidence on the effect of immunosuppressive drugs on infection with SARS-CoV-2. The effects of immunosuppressive drugs on similar pandemic coronaviruses may resemble the effects on SARS-CoV-2. Thus, we also included studies on the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). The study protocol was registered in PROSPERO (registration number CRD42020181137). We included randomized controlled trials (RCTs), cohort studies with a control group and case-control studies concerning humans ≥ 18 years old. We also included in-vitro studies and animal studies with a control group. Sixty-nine studies were included. Interestingly, MPA inhibits SARS-CoV-2 replication in-vitro. Clinical studies are needed to confirm the inhibitory effect of MPA on SARS-CoV-2 replication in-vivo. There are indications that corticosteroids and IL-6 inhibitors, like tocilizumab, can reduce mortality and prevent mechanical ventilation in patients with COVID-19. However, observational studies have contradictory results and the risk of bias is high. Thus, these results have to be confirmed in high-quality clinical trials before these drugs can be implemented as standard care. Based on the positive results of CNIs, mTOR inhibitors and thiopurine analogues in in-vitro studies with SARS-CoV and MERS-CoV, it would be interesting to investigate their effects on SARS-CoV-2 replication.


Rat soluble tumor-associated antigens inhibit chemically-induced mammary tumorigenesis in syngeneic rats.
This study examined whether soluble 66 and 51 kDa tumor-associated antigens (sTAA), isolated from the serum of rats with mammary cancer, possess specific suppressive effects on chemically-induced mammary tumorigenesis in syngeneic counterparts. Dimethylbenzanthracene (DMBA, 10 mg/rat, two administrations) was used to induce mammary tumors in 8-week-old Sprague Dawley rats. After the appearance of numerous tumors, preparations of sTAA (50 to 60 microg/rat in 0.5 ml sterile PBS) obtained from breast cancer patients (heterologous sTAA) or from syngeneic mammary tumor-bearing rats (syngeneic sTAA) were administered weekly for 12 weeks. The following groups of mammary tumor-bearing rats were studied: groups 1 and 3, control rats treated with saline; group 2, rats treated with heterologous sTAA; and group 4, rats treated with syngeneic sTAA. The experiment was terminated when tumors in 50% of the rats became ulcerous. The treatment with both types of sTAA significantly decreased, compared to controls and initial values, the yield and total area of the tumors. We conclude that syngeneic sTAA have tumor-suppressive properties, which are very similar to those in heterologous sTAA.


Comparison of antimüllerian hormone levels and antral follicle count as predictor of ovarian response to controlled ovarian stimulation in good-prognosis patients at individual fertility clinics in two multicenter trials.
To compare antimüllerian hormone (AMH) and antral follicle count (AFC) as predictors of ovarian response to controlled ovarian stimulation at individual fertility clinics. Retrospective analysis of individual study center data in two multicenter trials. Centers that provided >10 patients were included in the analysis. A total of 19 (n = 519 patients) and 18 study centers (n = 686 patients) participating in a long GnRH agonist trial (MERIT) and a GnRH antagonist trial (MEGASET), respectively. Infertile women of good prognosis. Long GnRH agonist or GnRH antagonist cycles. Correlation between AMH and AFC, and oocyte yield by each study center for each trial. Antimüllerian hormone was more strongly correlated with oocyte yield than AFC: r = 0.56 vs. r = 0.28 in the GnRH agonist cohort, and r = 0.55 vs. r = 0.33 in the GnRH antagonist cohort. The correlation was numerically higher for AMH than for AFC at a significantly higher proportion of study centers: 17 (89%) and 15 (83%) centers in the long GnRH agonist and GnRH antagonist trial, respectively. Assessment of the relative capacity of AMH and AFC for predicting oocyte yield demonstrated that AMH dominated the model: AMH, R(2) = 0.29 and 0.23; AFC: R(2) = 0.07 and 0.07; AMH + AFC: R(2) = 0.30 and 0.23 for long GnRH agonist and GnRH antagonist trials, respectively. Antimüllerian hormone was a stronger predictor of ovarian response to gonadotropin therapy than AFC at the study center level in both randomized trials utilizing GnRH agonist and GnRH antagonist protocols. Antral follicle count provided no added predictive value beyond AMH.


Texture analysis using generalized co-occurrence matrices.
We present a new approach to texture analysis based on the spatial distribution of local features in unsegmented textures. The textures are described using features derived from generalized co-occurrence matrices (GCM). A GCM is determined by a spatial constraint predicate F and a set of local features P = {(Xi, Yi, di), i = 1,..., m} where (Xi, Yi) is the location of the ith feature, and di is a description of the ith feature. The GCM of P under F, GF, is defined by GF(i, j) = number of pairs, pk, pl such that F(pk, pl) is true and di and dj are the descriptions of pk and pl, respectively. We discuss features derived from GCM's and present an experimental study using natural textures.


Excess risk in infant mortality among populations living in flood-prone areas in Bangladesh: A cluster-matched cohort study over three decades, 1988 to 2017.
The Ganges-Brahmaputra-Meghna river basin, running through Tibet, Nepal, Bhutan, Bangladesh, and northern India, is home to more than 618 million people. Annual monsoons bring extensive flooding to the basin, with floods predicted to be more frequent and extreme due to climate change. Yet, evidence regarding the long-term impacts of floods on children's health is lacking. In this analysis, we used high-resolution maps of recent large floods in Bangladesh to identify flood-prone areas over the country. We then used propensity score techniques to identify, among 58,945 mothers interviewed in six demographic population-based surveys throughout Bangladesh, matched cohorts of exposed and unexposed mothers and leverage data on 150,081 births to estimate that living in flood-prone areas was associated with an excess risk in infant mortality of 5.3 (95% CI 2.2 to 8.4) additional deaths per 1,000 births compared to living in non-flood-prone areas over the 30-y period between 1988 and 2017, with higher risk for children born during rainy (7.9, 95% CI: 3.3 to 12.5) vs. dry months (3.1, 95% CI: -1.1 to 7.2). Finally, drawing on national-scale, high-resolution estimates of flood risk and population distribution, we estimated an excess of 152,753 (64,120 to 241,386) infant deaths were attributable to living in flood-prone areas in Bangladesh over the past 30 y, with marked heterogeneity in attributable burden by subdistrict. Our approach demonstrates the importance of measuring longer-term health impacts from floods and provides a generalizable example for how to study climate-related exposures and long-term health effects.


Influenza and Workplace Productivity Loss in Working Adults.
Few studies have examined how acute respiratory illnesses (ARI) influence workplace productivity. We examined the association between laboratory-confirmed influenza and combined absenteeism/presenteeism. Linear regression was used to model the association between influenza (by seasonal vaccine status) and productivity loss over 7 to 17 days following symptom onset in 1278 employed adults in an influenza vaccine effectiveness study during the 2012 to 2013 through 2015 to 2016 seasons. Influenza was significantly associated with workplace productivity loss (P < 0.001), but there were no significant differences between virus type/subtypes or seasonal vaccine status. Regardless of vaccination, participants with H1N1pdm09, H3N2, or B infection had the greatest mean productivity loss (range, 67% to 74%), while those with non-influenza ARI had the lowest productivity loss (58% to 59%). Compared with non-influenza ARI, those with influenza lose an additional half day of work due to absenteeism/presenteeism over the week following symptom onset.


[Effect of Schistosoma japonicum Mr 22 600 particulated-antigen on dendritic cells and CD4+CD25+ regulatory T cells].
To study the role of Schistosoma japonicum Mr 22 600 particulated-antigen on dendritic cells (DCs) and CD4+CD25+ regulatory T cells. In in vitro experiments, DCs were pulsed with Sepharose 4B coupling rSj22.6/26GST and soluble rSj22.6/26GST, respectively. The surface molecules of DCs were detected by flow cytometry and the function of DCs was detected by mixed lymphocyte reaction. For the reduction of CD4+CD25+ T cells, DCs pulsed with Sepharose 4B coupling rSj22.6/26GST and soluble rSj22.6/26GST, respectively, were co-cultured with CD4+ T cells isolated from the spleen cells. The percentage of CD4+CD25+ Foxp3+ T cells in CD4+ T cells was detected by flow cytometry. In in vivo experiments, BALB/c mice were immunized with Sepharose 4B coupling rSj22.6/26GST, Freund's adjuvant emulsified rSj22.6/26GST, rSj22.6/26GST, Sepharose 4B, Freund's adjuvant and PBS, respectively. The percentage of DCs in draining lymph nodes and the percentage of CD4+CD25+Foxp3+ T cells in spleen cells were detected by flow cytometry. To analyze the inhibitory roles of CD4+CD25+ T cells on CD4+CD25- T cells, CD4+CD25+ T cells were separated from mice immunized with Sepharose 4B coupling rSj22.6/26GST and Freund's adjuvant emulsified rSj22.6/26GST, respectively, and co-cultured with CD4+CD25- T cells. The proliferation of cells was assessed by [3H] thymidine incorporation method. In vitro, the expression rate of the surface molecules of CD40, CD80 and CD86 on the soluble antigen pulsed DCs were (43.5 +/- 6.2)%, (37.7 +/- 0.1)%, and (71.4 +/- 1.4)%, respectively. But on the Sepharose 4B coupling antigen pulsed DCs, they were (31.2 +/- 5.4)%, (32.0 +/- 1.6)%, and (63.8 +/- 1.0)%, respectively, which suggested that the Sepharose 4B coupling rSj22.6/26GST had less stimulating roles on DCs maturation Furthermore, addition of DCs pulsed with Sepharose 4B coupling rSj22.6/26GST caused the expanding of CD4+CD25+ T cells. In vivo, immunization of Sepharose 4B coupling rSj22.6/26GST increased the number of CD4+CD25+ T cells. CD4+CD25+ T cells separated from Sepharose 4B coupling rSj22.6/26GST immunized mice had stronger inhibitory ability (cpm 1 420 +/- 335), compared with that of mice immunized with soluble antigen (cpm 3 558 +/- 147). In contrast to the Freund's adjuvant emulsified antigen, immunization with Sepharose 4B coupling rSj22.6/26GST increases the number of CD4+CD25+ T cells, which showed stronger inhibition on the CD4+ CD25- T cell proliferation, and the mechanism of which may be involved in DCs maturation.


Real-world outcomes of NSCLC patients receiving tissue or circulating tumor DNA-guided osimertinib treatment.
Osimertinib yields significant tumor responses and durations of progression-free survival (PFS) in patients with acquired T790M mutations. However, the evidence supporting liquid biopsy-guided treatment is still limited. This study examined the real-world benefits of osimertinib in patients with tissue or plasma T790M mutations. From January 2016 to June 2018, a total of 183 non-small-cell lung cancer patients were enrolled. The presence of the T790M mutation was assessed by either tissue or plasma. The PFS, overall survival, and tumor response rates of the patients were calculated and compared with those of previous clinical trials. T790M mutations were detected in 51.5% of the patients, including 64 of 140 (45.7%) who underwent liquid biopsies and 23 of 29 (79.3%) who underwent tumor biopsies. After excluding those in clinical trials, 46 patients received osimertinib, including 33 with positive plasma and 13 with positive tissue results for T790M mutations. The median PFS was 11.3 months (interquartile range: 5.2-NR) in all the T790M-positive patients and 10.1 months (interquartile range: 5.9-NR) in the plasma T790M-positive patients. The overall survival, meanwhile, was not reached, whereas the one-year survival rate was 66.1% in all the patients and 61.4% in those who were plasma T790M-positive. The objective response rate and disease control rate were 37.8% and 91.9% in all the patients and 34.6% and 92.3% in the plasma T790M-positive group, respectively. Using a Cox proportional hazards regression, we determined that male gender was a poor prognostic factor for PFS. In this retrospective real-world analysis, it was determined that both tissue and plasma T790M mutations can be used to guide treatment with osimertinib. Similar disease control rates and survival durations were observed in comparison to those of phase 3 clinical trials.


[Hygienic aspects of the use of compact plants for sewage treatment in small localities].
The waste-water system of small localities is an important measure for their sanitary well-being. At present, the firm "Ekobios" produces and installs block-module plants for sewage treatment in small localities.


The polarity sensitivity of the electrically stimulated human auditory nerve measured at the level of the brainstem.
Recent behavioral studies have suggested that the human auditory nerve of cochlear implant (CI) users is mainly excited by the positive (anodic) polarity. Those findings were only obtained using asymmetric pseudomonophasic (PS) pulses where the effect of one phase was measured in the presence of a counteracting phase of opposite polarity, longer duration, and lower amplitude than the former phase. It was assumed that only the short high-amplitude phase was responsible for the excitation. Similarly, it has been shown that electrically evoked compound action potentials could only be obtained in response to the anodic phases of asymmetric pulses. Here, experiment 1 measured electrically evoked auditory brainstem responses to standard symmetric, PS, reversed pseudomonophasic, and reversed pseudomonophasic with inter-phase gap (6 ms) pulses presented for both polarities. Responses were time locked to the short high-amplitude phase of asymmetric pulses and were smaller, but still measurable, when that phase was cathodic than when it was anodic. This provides the first evidence that cathodic stimulation can excite the auditory system of human CI listeners and confirms that this stimulation is nevertheless less effective than for the anodic polarity. A second experiment studied the polarity sensitivity at different intensities by means of a loudness balancing task between pseudomonophasic anodic (PSA) and pseudomonophasic cathodic (PSC) stimuli. Previous studies had demonstrated greater sensitivity to anodic stimulation only for stimuli producing loud percepts. The results showed that PSC stimuli required higher amplitudes than PSA stimuli to reach the same loudness and that this held for current levels ranging from 10 to 100% of the dynamic range.


Association of modifiable lifestyle behaviors with hypertension by various body mass index categories in Tianjin province of China: a cross-sectional study.
The present study was conducted to identify the difference of the relationship between lifestyle behaviors with hypertension (HTN) by various body mass index (BMI) categories. A cross-sectional study was conducted among Tianjin urban communities. A total of 26 438 subjects were randomly selected. The authors evaluated associations of lifestyle behaviors with HTN among normal, overweight, and obese adults using a hierarchical logistic model considering the gross domestic product of residence as socioeconomic proxy. A positive association was found between BMI and the risk of HTN among male and female subjects. Current smoking was associated with a higher risk of HTN in overweight (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.04-1.36) and obese groups (OR = 1.20, 95% CI = 1.03-1.53). There were statistically significant associations of current drinking with risk of HTN in normal weight (OR = 1.18, 95% CI = 1.01-1.31) and overweight groups (OR = 1.22, 95% CI = 1.07-1.40). The prevention of overweight and obesity is important in preventing HTN. Additionally, adherence to healthy lifestyle is associated with less risk of HTN in various BMI categories.


Accumulation of Immature Intron-containing CD44 Gene Transcripts in Breast Cancer Tissues.
Background: Disorderly expression of the CD44 gene is a characteristic feature of many common types of human malignancy. The explanation for the diversity, abundancy, and abnormally large size of the resulting transcripts is under investigation. Methods and Results: This study used reverse transcription-polymerase chain reaction (RT-PCR)/Southern blot hybridization to examine the expression of the CD44 gene in fresh tissue samples from 21 breast cancers and 11 matched non-neoplastic breast tissue specimens from the same patients. Using probes for several exons and for a noncoding region (intron 9) of the gene, it was found that the previously described elevated levels of CD44 transcripts in malignant tumors of this organ include many unusual, alternatively spliced isotypes as well as immature forms that retain this intron and probably several others. All of the exons that were tested were involved in the disorderly overexpression of this gene observed in all of the cancer tissues, and we were able to detect retention of the intron 9 sequence in 14 (67%) of the 21 tumor samples. In contrast, it was possible to detect signals in only 3 (27%) of the 11 samples from nonmalignant breast tissue with this probe, and these were extremely faint. Conclusions: These findings imply that there is a profound disorder in the regulation of production, splicing, and processing of CD44 pre-mRNA in breast cancer tissues comparable to that described in tumors of many other organs. The clinical implication of this information is that analysis of tissue samples containing borderline or suspected premalignant lesions for the presence of these molecular abnormalities, which appear to be characteristic of neoplasia, may in due course help assessment of individual patient prognosis and optimization of treatment.


Exceptional modulation of upconversion and downconversion near-infrared luminescence in Tm/Yb-codoped ferroelectric nanocomposite by nanoscale engineering.
The emission properties of lanthanide ions have been extensively investigated for their interesting physical processes and enormous applications. Conventional strategies have been used to modify luminescence properties such as temperature, pressure, and modifying components. However, the traditional methods are volatile and irreversible, which is unconducive for some optoelectronic applications. In this article, the electromechanical softness of the ferroelectric lattice is employed, which makes the strong coupling relationship between the electric field and the photonic properties of lanthanide ions. The emission intensity of the Tm3+:3H4-4H6 and 3F4-4H6 transitions was exceptionally enhanced by 2.6 and 3.2 times via ferroelectric polarization, respectively. Meanwhile, the luminescence response presents excellent reversibility and nonvolatility. This study provides a unique proposal for designing highly integrated stimuli-responsive photonic materials toward a variety of applications.


The chemopreventive effect of withaferin A on spontaneous and inflammation-associated colon carcinogenesis models.
Chemopreventive effects and associated mechanisms of withaferin A (WA) against intestinal and colon carcinogenesis remain unknown. We investigated the chemopreventive effect of WA on transgenic adenomatous polyposis coli (APCMin/+) mouse and chemically induced azoxymethane/dextran sodium sulfate (AOM/DSS) models of intestinal and colon carcinogenesis. Oral WA administration (4 and 3 mg/kg) inhibited tumor initiation and progression of intestinal polyps formation in APCMin/+ mice and colon carcinogenesis in the AOM/DSS mouse model. WA-administered mice showed a significant reduction in both number [duodenum, 33% (P > 0.05); jejunum, 32% (P < 0.025); ileum, 43% ( P < 0.001); and colon 59% (P < 0.01] and size of polyps in APCMin/+ mice compared with the respective controls. Similarly, tumor multiplicity was significantly reduced (P < 0.05) in the colon of WA-administered AOM/DSS mice. Pathological analysis showed reduced adenomas and tissue inflammation in WA-administered mouse models. Molecular studies suggested that WA inhibited the expression of inflammatory (interluekin-6, tumor necrosis factor-alpha and cyclooxygenase-2), pro-survival (pAKT, Notch1 and NF-κB) markers in APCMin/+ and AOM/DSS models. The results suggest that WA is a potent agent for preventing colon carcinogenesis and further investigation is required to show clinical utility of the agent.


How can theory predict the selectivity of palladium-catalyzed cross-coupling of pristine aromatic molecules?
The new approach for palladium-catalyzed cross-coupling of two non-activated aromatic compounds (D. R. Stuart, K. Fagnou, Science 2007, 316, 1172) was studied theoretically. The energetic span model (S. Kozuch, S. Shaik, Acc. Chem. Res. 2011, 44, 101, and references therein) was employed to analyze the kinetic behavior of the catalytic cycle. The computed energy profile, combined with the energetic span model, accounts for the experimental selectivity, which favors the hetero-coupling of benzene with indole. This selectivity is driven by a fine balance of the entropic contributions and the high ratio of concentrations used for benzene over indole. This analysis may allow future theoretical predictions of how different aromatic compounds can be effectively coupled.


Fish By-Product Use as Biostimulants: An Overview of the Current State of the Art, Including Relevant Legislation and Regulations within the EU and USA.
Crop production systems have adopted cost-effective, sustainable and environmentally friendly agricultural practices to improve crop yields and the quality of food derived from plants. Approaches such as genetic selection and the creation of varieties displaying favorable traits such as disease and drought resistance have been used in the past and continue to be used. However, the use of biostimulants to promote plant growth has increasingly gained attention, and the market size for biostimulants is estimated to reach USD 4.14 billion by 2025. Plant biostimulants are products obtained from different inorganic or organic substances and microorganisms that can improve plant growth and productivity and abate the negative effects of abiotic stresses. They include materials such as protein hydrolysates, amino acids, humic substances, seaweed extracts and food or industrial waste-derived compounds. Fish processing waste products have potential applications as plant biostimulants. This review gives an overview of plant biostimulants with a focus on fish protein hydrolysates and legislation governing the use of plant biostimulants in agriculture.


Calibration Method for ML Estimation of 3D Interaction Position in a Thick Gamma-Ray Detector.
High-energy (> 100 keV) photon detectors are often made thick relative to their lateral resolution in order to improve their photon-detection efficiency. To avoid issues of parallax and increased signal variance that result from random interaction depth, we must determine the 3D interaction position in the imaging detector. With this goal in mind, we examine a method of calibrating response statistics of a thick-detector gamma camera to produce a maximum-likelihood estimate of 3D interaction position. We parameterize the mean detector response as a function of 3D position, and we estimate these parameters by maximizing their likelihood given prior knowledge of the pathlength distribution and a complete list of camera signals for an ensemble of gamma-ray interactions. Furthermore, we describe an iterative method for removing multiple-interaction events from our calibration data and for refining our calibration of the mean detector response to single interactions. We demonstrate this calibration method with simulated gamma-camera data. We then show that the resulting calibration is accurate and can be used to produce unbiased estimates of 3D interaction position.


Performance of materials used for biological personal protective equipment against blood splash penetration.
For occupational safety, healthcare workers must select and wear appropriate personal protective equipment (PPE), protective clothing, and masks as countermeasures against exposure to infectious body fluids and blood splash. It is important for healthcare workers to ensure the protective performance of each PPE against penetration of pathogens. The International Standards Organization (ISO) 22609 test evaluates the effectiveness of medical facemasks to protect against penetration of splashed synthetic blood. However, in this method, the protective performance is determined only visually, without quantification of leaked liquid volume. Therefore, in this study, we modified the ISO 22609 test method to quantify the volume of leaked liquid and obtain a more accurate assessment of the protection performance. We tested non-woven and woven materials used for masks or protective clothing, and the performance of each material was classified using this new method. We found that the quantity of leaked synthetic blood was dependent on the structural characteristics of each material. These findings will allow healthcare workers to select the most appropriate PPE for a given situation or task.


Adaptation to herbivory and detritivory drives the convergent evolution of large abdominal cavities in a diverse freshwater fish radiation (Otophysi: Characiformes).
Convergent evolution is often interpreted as evidence of natural selection favoring an optimal phenotype during adaptation. Morphological convergence is frequently found among lineages that converge on diet, but most studies have focused on morphological traits that relate exclusively to food handling and processing. In vertebrates, there is a strong inverse relationship between intestine length and trophic level. However, little is known about whether adaptation to a low trophic level influences the evolution of abdominal cavities that can accommodate larger intestines. Here, I reconstruct the evolutionary history of trophic ecology and examine abdominal cavity shape across 157 species of the fish order Characiformes to determine whether adaptation to an herbivorous-detritivorous diet drives convergent evolution of large abdominal cavities. Herbivorous-detritivorous species evolved significantly larger abdominal cavities than other trophic groups and repeatedly converged on a similar abdominal cavity morphology. Other trophic groups evolved abdominal cavity morphologies either stochastically or by selective pressures from an untested ecological character. These findings demonstrate that the selective demands of a larger intestinal tract promote the repeated convergence of a large abdominal cavity within herbivorous-detritivorous characiform fishes, while allowing other lineages to evolve randomly or adapt in response to other selection pressures, contributing to the overall body shape diversity of the order.


Importance of adequate immunosuppressive therapy for the recovery of patients with "life-threatening" severe exacerbation of chronic hepatitis B.
Hepatitis B virus (HBV) re-activation often occurs spontaneously or after withdrawal of immunosuppressive therapy in patients with chronic hepatitis B. Severe exacerbation, sometimes developing into fulminant hepatic failure, is at high risk of mortality. The efficacy of corticosteroid therapy in "clinically severe" exacerbation of chronic hepatitis B has not been well demonstrated. In this study we evaluated the efficacy of early introduction of high-dose corticosteroid therapy in patients with life-threatening severe exacerbation of chronic hepatitis B. Twenty-two patients, 14 men and 8 women, were defined as "severe" exacerbation of chronic hepatitis B using uniform criteria and enrolled in this study. Eleven patients were treated with corticosteroids at 60 mg or more daily with or without anti-viral drugs within 10 d after the diagnosis of severe disease ("early high-dose" group) and 11 patients were either treated more than 10 d or untreated with corticosteroids ("non-early high-dose" group). Mean age, male-to-female ratio, mean prothrombin time (PT) activity, alanine transaminase (ALT) level, total bilirubin level, positivity of HBeAg, mean IgM-HBc titer, and mean HBV DNA polymerase activity did not differ between the two groups. Ten of 11 patients of the "early high-dose" group survived, while only 2 of 11 patients of the "non-early high-dose" group survived (P<0.001). During the first 2 wk after the introduction of corticosteroids, improvements in PT activities and total bilirubin levels were observed in the "early high-dose" group. Both ALT levels and HBV DNA polymerase levels fell in both groups. The introduction of high-dose corticosteroid can reverse deterioration in patients with "clinically life-threatening" severe exacerbation of chronic hepatitis B, when used in the early stage of illness.


The condensin complex governs chromosome condensation and mitotic transmission of rDNA.
We have characterized five genes encoding condensin components in Saccharomyces cerevisiae. All genes are essential for cell viability and encode proteins that form a complex in vivo. We characterized new mutant alleles of the genes encoding the core subunits of this complex, smc2-8 and smc4-1. Both SMC2 and SMC4 are essential for chromosome transmission in anaphase. Mutations in these genes cause defects in establishing condensation of unique (chromosome VIII arm) and repetitive (rDNA) regions of the genome but do not impair sister chromatid cohesion. In vivo localization of Smc4p fused to green fluorescent protein showed that, unexpectedly, in S. cerevisiae the condensin complex concentrates in the rDNA region at the G2/M phase of the cell cycle. rDNA segregation in mitosis is delayed and/or stalled in smc2 and smc4 mutants, compared with separation of pericentromeric and distal arm regions. Mitotic transmission of chromosome III carrying the rDNA translocation is impaired in smc2 and smc4 mutants. Thus, the condensin complex in S. cerevisiae has a specialized function in mitotic segregation of the rDNA locus. Chromatin immunoprecipitation (ChIP) analysis revealed that condensin is physically associated with rDNA in vivo. Thus, the rDNA array is the first identified set of DNA sequences specifically bound by condensin in vivo. The biological role of higher-order chromosome structure in S. cerevisiae is discussed.


Improvement of the optical signal-to-noise ratio in common-path holographic storage by use of a polarization-controlling media structure.
A holographic storage arrangement with common-path optics is likely to suffer from degradation of the optical signal-to-noise ratio (SNR) owing to scattering of the reference beam. Instead of the conventional method of spatial separation between the reference beam and a reconstruction beam, adoption of a combined spatial and polarization separation is proposed. To achieve polarization separation by using a photopolymer as the recording material, a media structure including retardation films and a reflection layer is proposed such that the polarization states of the two beams are the same inside the material but orthogonal outside. Preliminary experiments to show the feasibility of this idea for improving optical SNR are also demonstrated.


Experimental Pseudomonas pneumonia in leukopenic dogs: comparison of therapy with antibiotics and granulocyte transfusions.
Pseudomonas aeruginosa pneumonia was produced in dogs with radiation-induced leukopenia to study the comparative efficacy of several different therapies. In a randomized control trial, five treatment regimens were compared: no antibiotics or granulocytes (controls), gentamicin (5 mg/kg/day), carbenicillin (500 mg/kg/day), gentamicin and carbenicillin (same dosages), and daily granulocyte transfusion (minimum 5 x 10(9) cells/day) plus gentamicin (5 mg/kg/day). The most effective therapy was gentamicin plus granulocyte transfusions. Gentamicin alone was not significantly better than no specific therapy. Carbenicillin with or without gentamicin gave intermediate results. This study further supports the utility of granulocyte replacement therapy of infections in severely granulocytopenic subjects. The results also indicate that the relative value of granulocyte transfusions depends upon the specific antibiotic regimen with which these transfusions are compared.


A Review of Calibration Transfer Practices and Instrument Differences in Spectroscopy.
Calibration transfer for use with spectroscopic instruments, particularly for near-infrared, infrared, and Raman analysis, has been the subject of multiple articles, research papers, book chapters, and technical reviews. There has been a myriad of approaches published and claims made for resolving the problems associated with transferring calibrations; however, the capability of attaining identical results over time from two or more instruments using an identical calibration still eludes technologists. Calibration transfer, in a precise definition, refers to a series of analytical approaches or chemometric techniques used to attempt to apply a single spectral database, and the calibration model developed using that database, for two or more instruments, with statistically retained accuracy and precision. Ideally, one would develop a single calibration for any particular application, and move it indiscriminately across instruments and achieve identical analysis or prediction results. There are many technical aspects involved in such precision calibration transfer, related to the measuring instrument reproducibility and repeatability, the reference chemical values used for the calibration, the multivariate mathematics used for calibration, and sample presentation repeatability and reproducibility. Ideally, a multivariate model developed on a single instrument would provide a statistically identical analysis when used on other instruments following transfer. This paper reviews common calibration transfer techniques, mostly related to instrument differences, and the mathematics of the uncertainty between instruments when making spectroscopic measurements of identical samples. It does not specifically address calibration maintenance or reference laboratory differences.


Bacteroides koreensis sp. nov. and Bacteroides kribbi sp. nov., two new members of the genus Bacteroides.
Three bacterial isolates from human faeces, YS-aM39T, R2F3-3-3T and R2F3-5-1, were characterized as Gram-negative, strictly anaerobic, non-spore-forming, non-motile, and rod-shaped. Isolate YS-aM39T formed a distinct line of descent, showing greatest 16S rRNA gene sequence relatedness with R2F3-3-3T (97.5 %), R2F3-5-1 (97.5 %), Bacteroides ovatus (98.8 %) and Bacteroides xylanisolvens (97.2 %). Isolates R2F3-3-3T and R2F3-5-1 also formed a distinct line of descent, sharing greatest 16S rRNA gene sequence relatedness with B. ovatus (98.2 %) and B. xylanisolvens (97.2 %). The DNA G+C content of YS-aM39T was 44.8 mol%, that of R2F3-3-3T was 42.4 mol% and that of R2F3-5-1 was 42.6 mol%. The respiratory quinone of all three isolates was menaquinone MK-10. Polar lipid analysis identified phosphatidylethanolamine as the major lipid. The predominant fatty acids in all three isolates were anteiso-C15 : 0, iso-C15 : 0, C16 : 0 3-OH and iso-C17 : 0 3-OH. The major end products of glucose fermentation were acetic acid, lactic acid and formic acid. DNA-DNA hybridization data indicated that two isolates, YS-aM39T and R2F3-3-3T, represent a species distinct from B. ovatus and B. xylanisolvens. Finally, in this study, the two isolates represented two new species in the genus Bacteroides, for which we propose the names Bacteroides koreensis sp. nov. (type strain, YS-aM39T=KCTC 15520T=JCM 31393T) and Bacteroides kribbi sp. nov. (type strain, R2F3-3-3T=KCTC 15460T=JCM 31391T).


Effect of lecithin-bound iodine on the patients with bronchial asthma.
Lecithin-bound iodine (LBI), which has been reported to be a potential candidate for one of the therapeutic modalities for children with bronchial asthma based on the in-vitro study, was also found to be effective in relieving the symptoms of patients with childhood asthma. In addition to the in-vitro effect of downregulation and upregulation of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma), respectively, the clinical effect of LBI was highlighted through the concomitant upregulation of IFN-gamma production by the patients' lymphocytes, which were treated with LBI for 8 weeks. Therefore, LBI may reduce the signs of bronchial asthma by upregulating the synthesis of IFN-gamma that is a representative Th1 cytokine.


Respiratory inductance plethysmography in healthy infants: a comparison of three calibration methods.
Respiratory inductance plethysmography (RIP) measures respiration from body surface movements. Various techniques have been proposed for calibration in order that RIP may be used quantitatively. These include calculation of the proportionality constant of ribcage to abdominal volume change (K). The aims of this study were to 1) establish whether a fixed value of K could be used for calibration, and 2) compare this technique with multiple linear regression (MLR) and qualitative diagnostic calibration (QDC) in normal healthy infants. Recordings of pneumotachograph (PNT) flow and RIP were made during quiet (QS) and active sleep (AS) in 12 infants. The first 5 min in a sleep state were used to calculate calibration factors, which were applied to subsequent validation data. The absolute percentage error between RIP and PNT tidal volumes was calculated. The percentage error was similar over a wide range of K during QS. However, K became more critical when breathing was out of phase. A standard for K of 0.5 was chosen. There was good agreement between calibration methods during QS and AS. In the first minute following calibration during QS, the mean absolute errors were 3.5, 4.1 and 5.3% for MLR, QDC and fixed K respectively. The equivalent errors in AS were 11.5, 13.1 and 13.7% respectively. The simple fixed ratio method can be used to measure tidal volume with similar accuracy to multiple linear regression and qualitative diagnostic calibration in healthy unsedated sleeping infants, although it remains to be validated in other groups of infants, such as those with respiratory disease.


Membrane anchoring of diacylglycerol lactones substituted with rigid hydrophobic acyl domains correlates with biological activities.
Synthetic diacylglycerol lactones (DAG lactones) are effective modulators of critical cellular signaling pathways downstream of the lipophilic second messenger diacylglycerol that activate a host of protein kinase C (PKC) isozymes as well as other non-kinase proteins that share with PKC similar C1 membrane-targeting domains. A fundamental determinant of the biological activity of these amphiphilic molecules is the nature of their interactions with cellular membranes. This study characterizes the membrane interactions and bilayer anchoring of a series of DAG lactones in which the hydrophobic moiety is a 'molecular rod', namely a rigid 4-[2-(R-phenyl)ethynyl]benzoate moiety in the acyl position. Use of assays employing chromatic biomimetic vesicles and biophysical techniques revealed that the mode of membrane anchoring of the DAG lactone derivatives was markedly affected by the presence of the hydrophobic diphenyl rod and by the size of the functional unit at the terminus of the rod. Two primary mechanisms of interaction were observed: surface binding of the DAG lactones at the lipid/water interface and deep insertion of the ligands into the alkyl core of the lipid bilayer. These membrane-insertion properties could explain the different patterns of the PKC translocation from the cytosol to membranes that is induced by the molecular-rod DAG lactones. This investigation emphasizes that the side residues of DAG lactones, rather than simply conferring hydrophobicity, profoundly influence membrane interactions, and thus may further contribute to the diversity of biological actions of these synthetic biomimetic ligands.


Melanin-concentrating hormone (MCH) modulates C difficile toxin A-mediated enteritis in mice.
Melanin-concentrating hormone (MCH) is a hypothalamic orexigenic neuropeptide that regulates energy balance. However, the distribution of MCH and its receptor MCHR1 in tissues other than brain suggested additional, as yet unappreciated, roles for this neuropeptide. Based on previous paradigms and the presence of MCH in the intestine as well as in immune cells, its potential role in gut innate immune responses was examined. In human intestinal xenografts grown in mice, changes in the expression of MCH and its receptors following treatment with Clostridium difficile toxin A, the causative agent of antibiotic-associated diarrhoea in hospitalised patients, were examined. In colonocytes, the effect of C difficile toxin A treatment on MCHR1 expression, and of MCH on interleukin 8 (IL8) expression was examined. MCH-deficient mice and immunoneutralisation approaches were used to examine the role of MCH in the pathogenesis of C difficile toxin A-mediated acute enteritis. Upregulation of MCH and MCHR1 expression was found in the human intestinal xenograft model, and of MCHR1 in colonocytes following exposure to toxin A. Treatment of colonocytes with MCH resulted in IL8 transcriptional upregulation, implying a link between MCH and inflammatory pathways. In further support of this view, MCH-deficient mice developed attenuated toxin A-mediated intestinal inflammation and secretion, as did wild-type mice treated with an antibody against MCH or MCHR1. These findings signify MCH as a mediator of C difficile-associated enteritis and possibly of additional gut pathogens. MCH may mediate its proinflammatory effects at least in part by acting on epithelial cells in the intestine.


Effect of donor age on the susceptibility of erythrocytes and erythrocyte membranes to cumene hydroperoxide-induced oxidative stress.
A comparative study on erythrocytes and erythrocyte membranes of healthy elderly and young adults was carried out to understand how the antioxidant defense capacity is effected by aging. The levels of endogenous malondialdehyde and Ca(2+)-ATPase activity were taken as indices of oxidative damage. In addition, chemiluminescence measurements were performed on intact erythrocytes. The susceptibility of these parameters to in vitro cumene hydroperoxide, under low oxidant level that does not induce hemolysis, was also taken as an age-related indicator of the endogenous peroxidative potential of the erythrocytes. Our data showed that the content of malondialdehyde and Ca(2+)-ATPase activity did not change with age. Furthermore, the susceptibility of intact erythrocytes to oxidative stress did not change in the elderly group. However, under the same conditions erythrocyte membranes were more susceptible to oxidative damage in the elderly than young adults. Our results also showed that antioxidant defenses were overwhelmed in intact erythrocytes of the elderly at high concentrations of cumene hydroperoxide.


Cryopreservation Effects on Ram Sperm Ultrastructure.
Cryoprotectants are known to have protective effects against cryodamage to spermatozoa. In this study, the cryoprotective effects of two cryoprotectants (glycerol, ethylene glycol) and cryoprotectants/trehalose combinations on frozen-thawed ram spermatozoa were investigated at the ultrastructural level. For this purpose, ejaculates collected from Konya Merino rams were pooled and diluted with a tris-based extender containing additives, including 5% glycerol, 3% glycerol +60 mM trehalose, 1.5% glycerol +100 mM trehalose, 5% ethylene glycol, 3% ethylene glycol +60 mM trehalose, and 1.5% ethylene glycol +100 mM trehalose. They were all cooled to 5°C and then frozen in 0.25 mL French straws in liquid nitrogen. The samples were thawed at 37°C and centrifuged to remove the diluents. Then, they were processed using a scanning transmission electron microscope. In the statistical analysis, the number of ultrastructurally cryodamaged and intact spermatozoa were counted in longitudinal and transverse ultrathin sections in all groups by electron microscopic examination. The amount of intact spermatozoa in the groups containing 5% ethylene glycol and 1.5% ethylene glycol +100 mM trehalose was found to be higher than other groups (p < 0.05). As a result, it was suggested that the groups of 5% ethylene glycol and 1.5% ethylene glycol +100 mM trehalose provided the highest protection for the ultrastructural morphology of frozen-thawed Konya Merino ram spermatozoa among the groups.


Combined methotrexate-dactinomycin: an effective therapy for low-risk gestational trophoblastic neoplasia.
The objective of this study is to examine the outcomes of combined chemotherapy using methotrexate and dactinomycin in the management of women with low-risk gestational trophoblastic neoplasia (GTN). The primary outcome is the total number of cycles of chemotherapy required to achieve a normal level of human chorionic gonadotropin (hCG). The secondary outcome is treatment-related toxicity. A retrospective chart review of all patients with GTN treated between 1996-2007 and 1991-2007 was performed at the Alberta Cross Cancer Institute and the British Columbia Cancer Agency, respectively. Patients with low-risk GTN, treated with 0.6 mg/m(2) dactinomycin (days 1 and 2) and methotrexate 100mg/m(2) were included. Toxicities were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events. The number of cycles to achieve normalization of hCG was determined, and multivariate analyses were performed to identify factors associated with treatment duration. One hundred women were eligible. The average age was 29 years (range 15-46). The median number of cycles to achieve a normal hCG was 3 (range 1-11). Two patients required second-line treatment and one patient chose to proceed with hysterectomy. Ninety-eight percent of patients were primarily cured with this regimen, and 2 were cured with second line treatment. Grade 3 and 4 hematologic toxicities were experienced by 12% and 8% of patients, respectively. Grade 2 and 3 stomatitis or mucositis were noted in 44% and 3% of patients, respectively. Low-risk GTN is reliably and rapidly cured with combined methotrexate-dactinomycin. Toxicity is modest.


Profile of Secondary Glaucoma in a Tertiary Eye Hospital of Eastern Nepal.
To determine the clinical profile and causes of various types of secondary glaucoma. This was a hospital-based cross-sectional study conducted in a tertiary eye hospital of eastern Nepal from 1st June to 30th November, 2017. Patients who met the criteria for secondary glaucoma underwent detailed ophthalmic examination. Out of 7079 patients diagnosed with glaucoma or glaucoma suspects, 528 (7.4%) had secondary glaucoma. The mean age at presentation was 52 ± 17 years with male to female ratio of 1.5:1. The most common cause was lens induced 173 (32.8%) followed by neovascular 107 (20.3%), steroid induced 86 (16.3%), traumatic 76 (14.4%), post-vitrectomy 17 (3.2%), uveitic 11 (2.1%), pseudophakic 10 (1.9%), aphakic 8 (1.5%), post-keratoplasty 5 (0.9%) and miscellaneous included 35 (6.6%). Post-traumatic 31 (29.5%) was more prevalent below 41 years while lens induced glaucoma 86 (49%) above 60 years of age. At presentation, the average IOP was 40 ± 11 mmHg. 36 (6.8%) had no light perception in the presenting eye and a large number of participants 307 (58.1%) presented with visual acuity of <3/60 to perception of light. Glaucomatous optic atrophy was found in 22 (9.0%) cases. The causes of secondary glaucoma are diverse, lens induced glaucoma being most common. Most patients present late with poor vision, high IOP and even glaucomatous optic atrophy. So, early identification and treatment of the causes is important so that we can prevent the burden of blindness due to secondary glaucoma.


Rapid and selective alterations in the expression of cellular genes accompany conditional transcription of Ha-v-ras in NIH 3T3 cells.
Hormone treatment of NIH 3T3 cells that contain recombinant fusions between the mouse mammary virus long terminal repeat and the v-ras gene of Harvey murine sarcoma virus results in conditional expression of the ras p21 gene product. Levels of ras mRNA and p21 are maximal after 2 to 4 h of hormone treatment. Analysis of cellular RNA by Northern blotting and nuclease S1 protection assays indicates that the expression of two cellular RNA species increases with kinetics similar to v-ras: v-sis-related RNA and retrovirus-related VL30 RNA. Run-on transcription in isolated nuclei shows that the increase in v-sis-related RNA is not dependent on transcription and therefore must arise by a post-transcriptional mechanism. The increase in VL30 expression is a transcriptional effect. Hormone treatment of normal NIH 3T3 cells has no effect on the expression of these DNA sequences. These results suggest that v-ras stimulation of autocrine factors may play a role in transformation of cells by this gene and also suggest a reverse genetic strategy to determine the nucleic acid sequences and cellular factors involved in the regulation of gene expression that is observed.


Apple Watch Sleep and Physiological Tracking Compared to Clinically Validated Actigraphy, Ballistocardiography and Polysomnography.
This paper investigates the performance of the latest Apple Watch (Series 8, released September 2022) in comparison with research grade devices. The Apple Watch was compared to wrist worn actigraphy, non-contact ballistocardiography (BCG) placed in the bed and evaluated with polysomnography (PSG) as a reference system. Sleep analysis and individual cardiorespiratory parameters were measured from the Apple Watch. The Apple Watch performed well for identifying sleep-wake states but had difficulty identifying the sleep stages compared to the reference PSG system. Physiological parameters obtained from the Apple Watch compared well with measurements of the other devices in the study.Clinical Relevance- Consumer devices are readily available and inexpensive compared to clinical devices. A consumer device that can provide accurate physiological data equivalent to a clinical device would let researchers and clinicians collect data without the intrusive nature of a clinical device.


Nonlinear chiro-optical amplification by plasmonic nanolens arrays formed via directed assembly of gold nanoparticles.
Metal nanoparticle assemblies are promising materials for nanophotonic applications due to novel linear and nonlinear optical properties arising from their plasmon modes. However, scalable fabrication approaches that provide both precision nano- and macroarchitectures, and performance commensurate with design and model predictions, have been limiting. Herein, we demonstrate controlled and efficient nanofocusing of the fundamental and second harmonic frequencies of incident linearly and circularly polarized light using reduced symmetry gold nanoparticle dimers formed by surface-directed assembly of colloidal nanoparticles. Large ordered arrays (>100) of these C∞v heterodimers (ratio of radii R1/R2 = 150 nm/50 nm = 3; gap distance l = 1 ± 0.5 nm) exhibit second harmonic generation and structure-dependent chiro-optic activity with the circular dichroism ratio of individual heterodimers varying less than 20% across the array, demonstrating precision and uniformity at a large scale. These nonlinear optical properties were mediated by interparticle plasmon coupling. Additionally, the versatility of the fabrication is demonstrated on a variety of substrates including flexible polymers. Numerical simulations guide architecture design as well as validating the experimental results, thus confirming the ability to optimize second harmonic yield and induce chiro-optical responses for compact sensors, optical modulators, and tunable light sources by rational design and fabrication of the nanostructures.


Differential DNA extraction of challenging simulated sexual-assault samples: a Swiss collaborative study.
In sexual-assault cases, autosomal DNA analysis of gynecological swabs is a challenge, as the presence of a large quantity of female material may prevent detection of the male DNA. A solution to this problem is differential DNA extraction, but there is no established best practice for this. We decided to test the efficacy of a number of different protocols on simulated casework samples. Four difficult samples were sent to the nine Swiss laboratories active in forensic genetics. In each laboratory, staff used their routine protocols to separate the epithelial-cell fraction, enriched with the non-sperm DNA, from the sperm fraction. DNA extracts were then sent to the organizing laboratory for analysis. Estimates of male:female DNA ratio without differential DNA extraction ranged from 1:38 to 1:339, depending on the semen used to prepare the samples. After differential DNA extraction, most of the ratios ranged from 1:12 to 9:1, allowing detection of the male DNA. Compared with direct DNA extraction, cell separation resulted in losses of 94-98% of the male DNA. As expected, more male DNA was generally present in the sperm than in the epithelial-cell fraction. However, for about 30% of the samples, the reverse trend was seen. The recovery of male and female DNA was highly variable, depending on the laboratory involved. An experimental design similar to the one used in this study may be of assistance for local protocol testing and improvement.


Patient-reported outcomes and adult patients' disease experience in the idiopathic inflammatory myopathies. report from the OMERACT 11 Myositis Special Interest Group.
The newly formed Outcome Measures in Rheumatology (OMERACT) Myositis Special Interest Group (SIG) was established to examine patient-reported outcome measures (PROM) in myositis. At OMERACT 11, a literature review of PROM used in the idiopathic inflammatory myopathies (IIM) and other neuromuscular conditions was presented. The group examined in more detail 2 PROM more extensively evaluated in patients with IIM, the Myositis Activities Profile, and the McMaster-Toronto Arthritis Patient Preference Disability Questionnaire, through the OMERACT filter of truth, discrimination, and feasibility. Preliminary results from a qualitative study of patients with myositis regarding their symptoms were discussed that emphasized the range of symptoms experienced: pain, physical tightness/stiffness, fatigue, disease effect on emotional life and relationships, and treatment-related side effects. Following discussion of these results and following additional discussions since OMERACT 11, a research agenda was developed. The next step in evaluating PROM in IIM will require additional focus groups with a spectrum of patients with different myositis disease phenotypes and manifestations across a range of disease activity, and from multiple international settings. The group will initially focus on dermatomyositis and polymyositis in adults. Qualitative analysis will facilitate the identification of commonalities and divergent patient-relevant aspects of disease, insights that are critical given the heterogeneous manifestations of these diseases. Based on these qualitative studies, existing myositis PROM can be examined to more thoroughly assess content validity, and will be important to identify gaps in domain measurement that will be required to develop a preliminary core set of patient-relevant domains for IIM.


Regulation of a segmentation stripe by overlapping activators and repressors in the Drosophila embryo.
Gene expression stripes in Drosophila melanogaster embryos provide a model for how eukaryotic promoters are turned on and off in response to combinations of transcriptional regulators. Genetic studies suggested that even-skipped (eve) stripe 2 is controlled by three gap genes, hunchback (hb), Kruppel (Kr), and giant (gt), and by the maternal morphogen bicoid (bcd). A direct link is established between binding sites for these regulatory proteins in the stripe 2 promoter element and the expression of the stripe during early embryogenesis. The bcd and hb protein binding sites mediate activation, whereas neighboring gt and Kr protein sites repress expression and establish the stripe borders. The stripe 2 element has the properties of a genetic on-off switch.


Sequestration of Antimonite by Zerovalent Iron: Using Weak Magnetic Field Effects to Enhance Performance and Characterize Reaction Mechanisms.
Many oxyanion-forming metals (As, Sb, Se, Tc, etc.) can be removed from water by adsorption and/or redox reactions involving iron oxides, including the oxides associated with zerovalent iron (ZVI). The rate of antimonite (Sb(III) hydrolysis species) removal by ZVI was determined in open, well-mixed batch reactors as a function of experimental factors, including aging of the ZVI, addition of Fe(II), Sb dose, mixing rate, pH, initial concentrations of Sb(III), etc. However, the largest effect observed was the roughly 6-8 fold increase in Sb(III) removal rate due to the application of a weak magnetic field (WMF) during the experiments. The WMF effect on Sb removal arises from stimulated corrosion and delayed passivation of the ZVI, as evidenced by time series correlation analysis of "geochemical" properties (DO, Fetot, Eh, and pH) measured synchronously in each experiment. The removal of Sb under the conditions of this study was mainly due to oxidation of Sb(III) to Sb(V) and adsorption and coprecipitation onto the iron oxides formed from accelerated corrosion of ZVI, as evidenced by Sb K-edge XANES, EXAFS, and XPS. The degree of the WMF enhancement for Sb(III) was found to be similar to the WMF effect reported previously for Sb(V), As(III), As(V), and Se(VI).


L-Carnitine Attenuates Cardiac Dysfunction by Ischemic Insults Through Akt Signaling Pathway.
We aim to investigate the cardioprotective effects of L-carnitine (LC) on cardiac function during ischemia and reperfusion (I/R) and contractile function of single cardiomyocyte. C57BL/6 J mice were randomly assigned to 5 groups: sham group; vehicle group, LC preconditioning group, LC preconditioning + LY294002 (a PI3K/Akt signaling pathway inhibitor) group (LC + LY), and LY294002 group (LY). The sham group was exposed to the open heart operation but not I/R, the other groups received 45 min ischemia/48 h reperfusion. At the end of reperfusion, echocardiography was performed on every mouse. In order to determine whether LC's cardioprotection could act directly at the level of cardiomyocytes, we also tested its effects on isolated cardiomyocytes under hypoxia condition. The expressions of p-PI3K, PI3K, Akt, p-Akt, Bax and Bcl-2 proteins were detected by immunoblotting. The results showed that LC preconditioning remarkably improved cardiac function after I/R, but the cardioprotective effect of LC was significantly weakened after the application of LY294002. We also found that LC could directly improve the contractile function of cardiomyocytes under hypoxia condition. The immunoblotting results showed that LC administration restrained myocardial apoptosis as evidenced by decreasing the level of Bax expression, increasing the levels of phosphorylation of Akt, PI3K, and Bcl-2 protein expression, but these were blocked by LYC94002. Thus, the cardioprotective effects of LC against myocardial ischemic damage and its effect on single cardiomyocyte under hypoxia may be associated with the PI3K/Akt signaling pathway.


[Prognosis and long-term results of treatment of patients with differentiated thyroid carcinoma].
Results of treatment of 67 patients with differentiated thyroid carcinoma were analyzed. Pathological changes in the thyroid residue structure were found in 42.3% of patients after subtotal resection of the thyroid gland (SRTG), 38.8% of the total number of patients were given inadequate suppressive therapy. Only 63.4% of women with thyroid carcinoma were found to have pathology of organs of the reproductive system. SRTG is thought to be an unreasonable volume of operative treatment. For the determination of strategy of treatment it is expedient to use the systems of risk assessment of MACIS, TNM, Clinical Class (University of Chicago).


Suitability and Sufficiency of Telehealth Clinician-Observed, Participant-Collected Samples for SARS-CoV-2 Testing: The iCollect Cohort Pilot Study.
The severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic calls for expanded opportunities for testing, including novel testing strategies such as home-collected specimens. We aimed to understand whether oropharyngeal swab (OPS), saliva, and dried blood spot (DBS) specimens collected by participants at home and mailed to a laboratory were sufficient for use in diagnostic and serology tests of SARS-CoV-2. Eligible participants consented online and were mailed a participant-collection kit to support collection of three specimens for SARS-CoV-2 testing: saliva, OPS, and DBS. Participants performed the specimen collection procedures during a telehealth video appointment while clinical observers watched and documented the suitability of the collection. The biological sufficiency of the specimens for detection of SARS-CoV-2 by reverse transcriptase-polymerase chain reaction and serology testing was assessed by laboratorians using visual inspection and quantification of the nucleic acid contents of the samples by ribonuclease P (RNase P) measurements. Of the enrolled participants,153/159 (96.2%) returned their kits, which were included in this analysis. All these participants attended their video appointments. Clinical observers assessed that of the samples collected, 147/153 (96.1%) of the saliva samples, 146/151 (96.7%) of the oropharyngeal samples, and 135/145 (93.1%) of the DBS samples were of sufficient quality for submission for laboratory testing; 100% of the OPS samples and 98% of the saliva samples had cycle threshold values for RNase P <30, indicating that the samples contained sufficient nucleic acid for RNA-PCR testing for SARS-CoV-2. These pilot data indicate that most participant-collected OPS, saliva, and DBS specimens are suitable and sufficient for testing for SARS-CoV-2 RNA and serology. Clinical observers rated the collection of specimens as suitable for testing, and visual and quantitative laboratory assessment indicated that the specimens were biologically sufficient. These data support the utility of participant-collected and mailed-in specimens for SARS-CoV-2 testing. RR2-10.2196/19054.


[Telemedicine--ready for use in the cardiological field?].
The changes in the demographic structure, the increasing multi-morbidity in connection with a rise in the number of chronic illnesses and the absence of an effective coordination of the different levels of health care services with its discontinuous processes and redundancies will increase the economic burdens in the health care system. The latest developments and appropriate logistic premises nowadays offer a realistic basis for implementing telemonitoring as a central service and information tool as well as an instrument controlling the information- and data-flow between patient, hospital and medical practitioner.


Optimising recruitment into a study of physical activity in older people: a randomised controlled trial of different approaches.
physical activity studies in older people often have poor recruitment. Including a questionnaire with the invitation would provide information about non-participants and selection bias, but could reduce recruitment. Telephone contact might encourage participation. to test the effects of different strategies for recruitment into a study of physical activity in older people. factorial randomised controlled trial. Randomisation by household into four groups: telephone contact plus questionnaire, telephone contact only, questionnaire only, neither. primary care, Oxfordshire, United Kingdom. 560 patients > or = 65 years randomly selected after exclusions. questionnaire to assess health, functional ability and physical activity. Telephone contact by the research nurse a week after sending study information. recruitment into physical activity study. telephone contact increased recruitment: contact 47.9% (134/280), no contact 37.9% (106/280), difference (adjusted for the clustering effect of household) 10.0% (95% CI 0.2-19.8). Questionnaire inclusion did not significantly reduce recruitment: no questionnaire 44.3% (124/280) questionnaire 41.4% (116/280) difference -2.9% (95% CI -12.7-7.0). telephone contact significantly increased recruitment and should be considered in studies where recruitment may be low. While inclusion of a questionnaire provided valuable information on non-participants and did not significantly reduce recruitment, an adverse recruitment effect could not be excluded.


Symptoms and otoscopic signs in bilateral and unilateral acute otitis media.
Bilateral acute otitis media (AOM) is considered more severe than unilateral AOM, and several guidelines recommend more active treatment and/or follow-up of bilateral AOM. We studied whether bilateral AOM is a clinically more severe illness than unilateral AOM by comparing symptoms and otoscopic signs between bilateral and unilateral AOM. Two hundred thirty-two children aged 6 to 35 months diagnosed with AOM were eligible. We surveyed the symptoms with a structured questionnaire and recorded the otoscopic signs systematically. Ninety-eight children had bilateral and 134 children unilateral AOM. Children with bilateral AOM were more often <24 months than children with unilateral AOM (87% vs 75%; P = .032). Fever (≥38°C) occurred in 54% and 36% (P = .006) and severe conjunctivitis in 16% and 44% (P = .047) of children with bilateral and unilateral AOM, respectively. In 15 other symptoms, we found no overall differences even when adjusted with age. We observed the following severe otoscopic signs in the bilateral and unilateral AOM group, respectively: moderate/marked bulging of tympanic membrane (63% and 40%; P = .001), purulent effusion (89% and 71%; P = .001), bulla formation (11% and 10%; P = .707), and hemorrhagic redness of tympanic membrane (7% and 10%; P = .386). Bilateral AOM seems to be a clinically only slightly more severe illness than unilateral AOM. Therefore, when assessing AOM severity, bilaterality should not be used as a determining criterion; instead, the child's symptomatic condition together with otoscopic signs should also be taken into consideration.


Ultrastrong Mode Confinement in ZnO Surface Plasmon Nanolasers.
Nanolasers with an ultracompact footprint can provide high-intensity coherent light, which can be potentially applied to high-capacity signal processing, biosensing, and subwavelength imaging. Among various nanolasers, those with cavities surrounded by metals have been shown to have superior light emission properties because of the surface plasmon effect that provides enhanced field confinement capability and enables exotic light-matter interaction. In this study, we demonstrated a robust ultraviolet ZnO nanolaser that can operate at room temperature by using silver to dramatically shrink the mode volume. The nanolaser shows several distinct features including an extremely small mode volume, a large Purcell factor, and a slow group velocity, which ensures strong interaction with the exciton in the nanowire.


Astrocytic MicroRNAs and Transcription Factors in Alzheimer's Disease and Therapeutic Interventions.
Astrocytes are important for maintaining cholesterol metabolism, glutamate uptake, and neurotransmission. Indeed, inflammatory processes and neurodegeneration contribute to the altered morphology, gene expression, and function of astrocytes. Astrocytes, in collaboration with numerous microRNAs, regulate brain cholesterol levels as well as glutamatergic and inflammatory signaling, all of which contribute to general brain homeostasis. Neural electrical activity, synaptic plasticity processes, learning, and memory are dependent on the astrocyte-neuron crosstalk. Here, we review the involvement of astrocytic microRNAs that potentially regulate cholesterol metabolism, glutamate uptake, and inflammation in Alzheimer's disease (AD). The interaction between astrocytic microRNAs and long non-coding RNA and transcription factors specific to astrocytes also contributes to the pathogenesis of AD. Thus, astrocytic microRNAs arise as a promising target, as AD conditions are a worldwide public health problem. This review examines novel therapeutic strategies to target astrocyte dysfunction in AD, such as lipid nanodiscs, engineered G protein-coupled receptors, extracellular vesicles, and nanoparticles.