Performance and data analysis aspects of the new DIII-D monostatic profile reflectometer system.
A new frequency-modulated profile reflectometer system, featuring a monostatic antenna geometry (using one microwave antenna for both launch and receive), has been installed on the DIII-D tokamak, providing a first experimental test of this measurement approach for profile reflectometry. Significant features of the new system are briefly described in this paper, including the new monostatic arrangement, use of overmoded, broadband transmission waveguide, and dual-polarization combination/demultiplexing. Updated data processing and analysis, and in-service performance aspects of the new monostatic profile reflectometer system are also presented. By using a raytracing code (GENRAY) to determine the approximate trajectory of the probe beam, the electron density (ne) profile can be successfully reconstructed with L-mode plasmas vertically shifted by more than 10 cm off the vessel midplane. Specifically, it is demonstrated that the new system has a capability to measure ne profiles with plasma vertical offsets of up to ±17 cm. Examples are also presented of accurate, high time and spatial resolution density profile measurements made over a wide range of DIII-D conditions, e.g., the measured temporal evolution of the density profile across a L-H transition.


Naltrexone in the treatment of heroin dependence: relationship with depression and risk of overdose.
This article examines the use of naltrexone in the treatment of heroin dependence. The relationship between naltrexone and depression as well as risk of overdose is examined. The existing literature is reviewed along with recent interim data from clinical trials underway in Victoria. Naltrexone is a recent addition to treatment for heroin dependence in Australia. The relationship between depression and naltrexone has been examined in previous literature. Underlying rates of depression in heroin users are high and treatment may resolve or exacerbate depression. Research to date demonstrates that the addition of naltrexone does not necessarily increase depression in patients. The risk of non-fatal heroin overdose is significantly elevated after naltrexone treatment as a result of reduced tolerance. Data from clinical trials underway in Victoria demonstrate a significantly elevated rate of non-fatal overdose in naltrexone patients compared to those in substitution maintenance treatment. The mortality rate subsequent to naltrexone treatment appears to be equivalent to or greater than that for untreated heroin users. Further research is required. Clinicians need to carefully monitor depression in patients, and warn patients of the risks of reduced tolerance to opiates following naltrexone treatment. Agonist treatments such as methadone, LAAM and buprenorphine carry much less risk of overdose.


Expression of CD40, CD44, bcl-2 antigens and rate of cell proliferation on fine needle aspirates from metastatic melanoma.
The clinical behaviour of melanoma is often unpredictable using clinical and histological criteria. Tumour cell markers related to cell cycle regulation, apoptosis, cell-cell interactions and cell proliferation might improve the possibility of predicting the clinical course of melanoma. The aim of the present study was to refine prognostic criteria by an immunocytochemical investigation of CD44, CD40, bcl-2 antigens and cell proliferation in tumour cells aspirated from metastases of malignant melanoma. CD40 is a cell surface receptor shown to be expressed by lymphomas as well as carcinomas, and is thought to play a central role in the process of tumour progression. CD44 is a transmembrane glycoprotein, which is involved in growth signal transmission of importance in the binding of tumour cells to endothelium, cell migration and enhancement of cell motility, which makes it of interest to study in relation to the metastasizing capacity of tumours. The bcl-2 protein is active in the process of programmed cell death (apoptosis) as an antiapoptotic agent and its expression may reflect tumour progression. Mean/median percentages of tumour cell positivity were 8.5/3.0 for CD40, 76.1/86.3 for CD44 and 7.4/3.3 for bcl-2. A significant correlation was observed between expression of apoptosis-associated bcl-2 antigen and overall survival (r = 0.33). The CD44 positive cell fraction was higher in patients with short overall survival than those with long survival but this difference was not statistically significant. The expression of CD40 did not correlate with overall survival. The mean/median proliferation fraction assessed by MIB-1 monoclonal antibody was 25.8/23.9 and showed a significant correlation with survival after diagnosis of melanoma metastasis (r = 0.32). Lack of bcl-2 expression and a high proportion of tumour cells expressing Ki-67 antigen are predictors of poor prognosis that are independent of the traditionally accepted Breslow's thickness of the primary melanomas.


Isolation of two bacteriophages from Bacillus larvae, PBL1 and PBL0.5, and partial characterization of PBL1.
Two temperate bacteriophages have been isolated from Bacillus larvae: PBL1 and PBL0 .5. Strains lysogenic for either of these phages are immune to lysis by the same phage but are sensitive to the other phage. PBL1 has an oval head, a non-contractile tail, and a base plate with a pin structure but no apparent tail fibres. The genome of PBL1 consists of double-stranded DNA with a molecular weight of 24.1 (+/-0.6) X 10(6), a G + C content (derived from melting temperature) of 41.5%, and cohesive ends. Restriction enzyme analysis permitted construction of a physical map of the genome.


Tumor immune microenvironment-modulated nanostrategy for the treatment of lung cancer metastasis.
As one of the most malignant tumors worldwide, lung cancer, fueled by metastasis, has shown rising mortality rates. However, effective clinical strategies aimed at preventing metastasis are lacking owing to its dynamic multi-step, complicated, and progressive nature. Immunotherapy has shown promise in treating cancer metastasis by reversing the immunosuppressive network of the tumor microenvironment. However, drug resistance inevitably develops due to inadequate delivery of immunostimulants and an uncontrolled immune response. Consequently, adverse effects occur, such as autoimmunity, from the non-specific immune activation and non-specific inflammation in off-target organs. Nanocarriers that improve drug solubility, permeability, stability, bioavailability, as well as sustained, controlled, and targeted delivery can effectively overcome drug resistance and enhance the therapeutic effect while reducing adverse effects. In particular, nanomedicine-based immunotherapy can be utilized to target tumor metastasis, presenting a promising therapeutic strategy for lung cancer. Nanotechnology strategies that boost the immunotherapy effect are classified based on the metastatic cascade related to the tumor immune microenvironment; the breaking away of primary tumors, circulating tumor cell dissemination, and premetastatic niche formation cause distant secondary site colonization. In this review, we focus on the opportunities and challenges of integrating immunotherapy with nanoparticle formulation to establish nanotechnology-based immunotherapy by modulating the tumor microenvironment for preclinical and clinical applications in the management of patients with metastatic lung cancer. We also discuss prospects for the emerging field and the clinical translation potential of these techniques.


A study of the impact of the 21-gene breast cancer assay on the use of adjuvant chemotherapy in women with breast cancer in a Mexican public hospital.
The majority of breast cancer patients in Mexico are treated through the public health system and >80% receive adjuvant chemotherapy. The aim of this prospective study was to characterize the impact of the Oncotype DX assay on adjuvant therapy decision making and the confidence in those decisions amongst public sector physicians in Mexico. Ninety-eight consecutive patients with ER+, HER2-, stage I-IIIa, N0/N1-3 node-positive breast cancer from the Instituto Nacional de Cancerología were eligible for the study. The primary endpoint was the overall change in treatment recommendations after receiving the assay results. Of 96 patients, 48% received a chemohormonal therapy recommendation prior to testing. Following receipt of results, treatment decisions changed for 31/96 (32%) patients, including 17/62 (27%) node-negative patients and 14/34 (41%) node-positive patients. The proportion of patients with a chemotherapy-based recommendation decreased from 48% pre- to 34% post-assay (P=0.024). 92% of physicians agreed that they were more confident in their treatment recommendation after ordering the assay. These results suggest that use of the 21-gene assay in the Mexican public health system has a meaningful impact on adjuvant treatment recommendations that may reduce the overall use of chemotherapy.


Synthesis and characterization of azobenzene-confined porphyrins.
A versatile synthetic method has been developed to incorporate photochromic azobenzene moieties into tetraphenylporphyrin frameworks in an orthogonal fashion, positioning the phenylazo substituents above and below the plane of the macrocycle. Surprisingly, photoisomerization is completely suppressed in the resulting azobenzene-confined porphyrins.


Delivery of monochorionic twins: lessons learned from the Twin Birth Study.
The current literature regarding the recommended mode of delivery of monochorionic-diamniotic twins is limited to small numbers, retrospective studies, and comparisons of outcomes of monochorionic-diamniotic twin pregnancies with those of dichorionic-diamniotic twin pregnancies instead of outcomes of trial of labor vs elective cesarean delivery of monochorionic-diamniotic twins. This study aimed to compare perinatal and maternal outcomes of planned cesarean delivery and planned vaginal delivery of monochorionic-diamniotic twins using the Twin Birth Study data. This study is a secondary analysis of the Twin Birth Study. Women were randomized from 32 weeks and 0 days gestation to 38 weeks and 6 days gestation to planned cesarean delivery or planned vaginal delivery. Twin A in the cephalic presentation and estimated weight of each twin between 1500 and 4000 grams were the inclusion criteria. Pregnancies complicated by fetal reduction after 13 weeks of gestation, lethal fetal anomaly, or contraindication to vaginal delivery were excluded. Elective delivery was planned between 37 weeks and 5 to 7 days of gestation and 38 weeks and 6 to 7 days of gestation. Perinatal and maternal outcomes of monochorionic-diamniotic twin pregnancies were compared between those randomized for planned cesarean delivery and those randomized for planned vaginal delivery. In addition, outcomes of monochorionic-diamniotic twin pregnancies were compared with those of dichorionic-diamniotic twin pregnancies. Out of the 1393 women in each arm, 346 (24.9%) women in the planned cesarean delivery arm and 324 (23.3%) women in the planned vaginal delivery arm had monochorionic-diamniotic twin pregnancies and were eligible for the first analysis. The rate of cesarean delivery was 39.2% in the planned vaginal delivery arm and was 91.3% in the planned cesarean delivery arm. There was no significant difference in gestational age at delivery between the groups (34.4±1.8 weeks vs 34.5±1.8 weeks; P=.78). No difference was found in maternal outcomes. As for perinatal outcomes, the rate of the primary adverse neonatal composite outcomes in twins A or twins B was similar in both the planned vaginal delivery and the planned cesarean delivery arms (twins A, 1.2% vs 1.2% [P=.92]; twins B, 1.2% vs 3.2% [P=.09]). Within the planned cesarean delivery arm, the rate of primary adverse neonatal composite outcome was higher in twins B than twins A (3.2% vs 1.2%; P=.03). There was no difference in the primary adverse neonatal composite outcome between twins A in the monochorionic-diamniotic group and the dichorionic-diamniotic group (1.2% vs 1.3%; P=.89) or between twins B in similar groups (2.3% vs 2.7%; P=.47). In monochorionic-diamniotic twin pregnancy between 32 weeks and 0 to 7 days of gestation and 38 weeks and 6 to 7 days of gestation, with twin A in a cephalic presentation, planned cesarean delivery did not decrease or increase the risk of fetal or neonatal death or serious neonatal morbidity, as compared with planned vaginal delivery.


Leuconostoc carnosum associated with spoilage of refrigerated whole cooked hams in Greece.
A polyphasic taxonomic approach was used to identify a major atypical group of gas-forming, arginine-negative lactic acid bacteria associated with spoilage of whole (nonsliced) refrigerated (4 degrees C) cooked hams produced in two Greek industrial meat plants. Biochemical characterization revealed that the ham isolates shared their phenotypic properties with Leuconostoc carnosum, Weissella viridescens, and Weissella hellenica. However, gas chromatographic analysis of cellular fatty acids clearly differentiated the ham isolates from the Weissella spp. None of the isolates contained eicosenoic acid (n-C20:1), which is typically synthesized by W. viridescens, but all strains contained high amounts of C 19cycl acid, which is absent in W. hellenica and has been found in trace amounts in W. viridescens. All strains had similar cellular fatty acid profiles, which were qualitatively similar to those of the cellular fatty acids of L. carnosum. In addition to the phenotypic and chemotaxonomic tests, three representative isolates were studied using a lactic acid bacteria database, which employs 16S and 23S HindIII restriction fragment length polymorphism patterns as operational taxonomic units in a numerical analysis. The isolate patterns were identical to those of the L. carnosum type strain, NCFB 2776T. Based on the polyphasic taxonomic approach, the dominating lactic acid bacteria group was identified as L. carnosum.


Transforming Psoriasis Care: Probiotics and Prebiotics as Novel Therapeutic Approaches.
Psoriasis is a chronic inflammatory skin disease with autoimmune pathological characteristics. Recent research has found a link between psoriasis, inflammation, and gut microbiota dysbiosis, and that probiotics and prebiotics provide benefits to patients. This 12-week open-label, single-center clinical trial evaluated the efficacy of probiotics (Bacillus indicus (HU36), Bacillus subtilis (HU58), Bacillus coagulans (SC208), Bacillus licheniformis (SL307), and Bacillus clausii (SC109)) and precision prebiotics (fructooligosaccharides, xylooligosaccharides, and galactooligosaccharides) in patients with psoriasis receiving topical therapy, with an emphasis on potential metabolic, immunological, and gut microbiota changes. In total, 63 patients were evaluated, with the first 42 enrolled patients assigned to the intervention group and the next 21 assigned to the control group (2:1 ratio; non-randomized). There were between-group differences in several patient characteristics at baseline, including age, psoriasis severity (the incidence of severe psoriasis was greater in the intervention group than in the control group), the presence of nail psoriasis, and psoriatic arthritis, though it is not clear whether or how these differences may have affected the study findings. Patients with psoriasis receiving anti-psoriatic local therapy and probiotic and prebiotic supplementation performed better in measures of disease activity, including Psoriasis Area and Severity Index, Dermatology Life Quality Index, inflammatory markers, and skin thickness compared with those not receiving supplementation. Furthermore, in the 15/42 patients in the intervention group who received gut microbiota analysis, the gut microbiota changed favorably following 12 weeks of probiotic and prebiotic supplementation, with a shift towards an anti-inflammatory profile.


Causally treatable, hereditary neuropathies in Fabry's disease, transthyretin-related familial amyloidosis, and Pompe's disease.
Most acquired neuropathies are treatable, whereas genetic neuropathies respond to treatment in Fabry's disease (FD), transthyretin-related familial amyloidosis (TTR-FA), and Pompe's disease (PD). This review summarizes and discusses recent findings and future perspectives concerning etiology, pathophysiology, clinical presentation, diagnosis, treatment, and outcome of neuropathy in FD, TTR-FA, and PD. Literature review. Neuropathy in FD concerns particularly small, unmyelinated, or myelinated sensory fibers (small fiber neuropathy [SFN]) and autonomic fibers, manifesting as acroparesthesias, Fabry's crises, or autonomous disturbances. FD neuropathy benefits from agalsidase alpha (0.2 mg/kg every second week intravenously) or from beta (1.0 mg/kg every second week intravenously). Neuropathy in TTR-FA is axonal and affects large and small sensory, motor, and autonomous fibers. Neuropathy in TTR-FA profits from liver transplantation and the TTR kinetic stabilizer tafamidis (20 mg/d). Neuropathy in PD particularly occurs in late-onset PD and manifests as mononeuropathy, polyneuropathy, or SFN. PD neuropathy presumably responds to alglucosidase-alpha (20 mg/kg every second week intravenously). Neuropathy in FD, TTR-FA, and PD is predominantly a SFN and can be the dominant feature in FD and TTR-FA. SFN in FD, TTR-FA, and PD needs to be recognized and benefits from enzyme replacement treatment or TT-kinetic stabilizers.


Treatment of polymorphic light eruption.
Polymorphic light eruption (PLE) is a highly prevalent photosensitivity disorder, estimated to affect 11-21% people in temperate countries. Typically, PLE appears as a recurrent pruritic eruption comprising papules and/or vesicles and/or plaques, which occurs on photo-exposed skin sites following sun exposure, and which heals without scarring. Commoner in females, the aetiology is uncertain, although there is evidence of an immune basis. We perform a review of the prophylaxis and treatment of this condition. While sun protection, corticosteroids and desensitization phototherapy are the mainstays of management, a range of anti-inflammatory and immunomodulatory agents are reported.


Utilization of Whole Exome Sequencing in Lethal Form of Multiple Pterygium Syndrome: Identification of Mutations in Embryonal Subunit of Acetylcholine Receptor.
The acetylcholine receptor (AChR) is a member of the superfamily of transmitter-gated ion channels having a critical role in controlling electrical signals between nerves and muscle cells. Disruptive mutations in genes encoding different subunits of AChR result in multiple pterygium syndrome (MPS), which can be associated with a severe prenatally lethal presentation. This study aimed to investigate the etiology of lethal MPS (LMPS) in two consanguineous families with a history of miscarriages. DNA was extracted from a tissue sample of two aborted fetuses (probands) from two different families with a history of spontaneous miscarriages. Parental peripheral blood samples were collected for confirmatory analysis and follow-up testing. Whole-exome sequencing (WES) was performed on DNA from the probands. The results were confirmed and segregated by Sanger sequencing. Moreover, protein structure evaluations were accomplished. We identified a homozygous frameshift mutation of c.753_754delCT (p.V253fs*44) and a homozygous missense mutation of c.715C>T (p.Arg239Cys) in the CHRNG gene. Both aborted fetuses had pterygium, severe arthrogryposis, and fetal hydrops with cystic hygroma, being compatible with LMPS. The heterozygous state was confirmed in parents for both CHRNG variants. Likewise, CHRNG mutation was predicted to display the damaging effects by lowering the number of helixes and modifying the surface electrostatic potential. The present study identified rare sequence variants in the CHRNG gene in aborted fetuses from consanguineous couples with recurrent miscarriage history. WES is a comprehensive and cost-effective approach to study heterogeneous diseases including MPS. Such findings can improve our knowledge of MPS databases, particularly for genetic counseling of high-risk families and preimplantation genetic diagnosis.


Pathophysiology of cardiorenal syndrome in patients with heart failure: potential therapeutic targets.
Despite the development of pharmacological inventions and new nonpharmacological techniques to prevent and treat heart failure (HF), the mortality rate in patients with symptomatic HF remains high. To conquer these difficulties, the pathophysiology of HF should be considered within a wide range of views. Given the diverse mechanisms of HF pathophysiology, renal and cardiac functions have close and complementary interconnections. Recent studies have suggested that communication between the kidney and heart through bidirectional pathways causes significant pathological changes. This review summarizes the pathophysiology of cardiorenal syndrome (CRS) from three different viewpoints, namely, underlying chronic kidney disease, worsening renal function during hospitalization due to HF, and resistance to diuretics. We also summarize the presently available data on the pathophysiology of CRS, identify the challenges associated with some clinical approaches, and explore the potential therapeutic target for CRS.


[Recourse to care and morbidity of the homeless in the Paris district].
The disparities of access to care and morbidity according to different socio-economic characteristics are highlighted over about thirty years; what is the situation with regard to the homeless, the least provided for, who in some sense lie at the limits of the social scale? We present data on hospitalizations, ambulatory care and the morbidity declared by the homeless revealed in the INED survey of February-March 1995 in the Paris region. We tried to compare hospitalizations and physician care of the homeless with the population of "ordinary households" in the same region on the basis of different statistical sources. Hospitalizations are considerably more numerous in this group than in the rest of the population which indicates that the homeless are more exposed to diseases and accidents; on the other hand, taking into account any possible errors of observation, the homeless and the general population seem to have the same rate of recourse to outpatient doctor treatment. Is this also the case for complementary examinations, biological tests and medical imagery?


Some epidemiologic features of motorcycle collision injuries. II. Factors associated with severity of injuries.
Male drivers sustained relatively more serious motorcycle collision injuries than did male passengers, female drivers, or female passengers. For male drivers, severity of injury was related to age. The relative frequency of serious head injury was highest for drivers not wearing helmets who were involved in collisions at low or high speeds. Severity of injury was related to speed at the time of collision but not in all types of collisions. Factors associated with the incidence of collisions were not identical to those related to the severity of the injury sustained.


DNA vaccination of HSP105 leads to tumor rejection of colorectal cancer and melanoma in mice through activation of both CD4 T cells and CD8 T cells.
We report that HSP105, identified by serological identification of antigens by recombinant expression cloning (SEREX), is overexpressed in a variety of human cancers, including colorectal, pancreatic, thyroid, esophageal, and breast carcinoma, but is not expressed in normal tissues except for the testis. The amino acid sequences and expression patterns of HSP105 are very similar in humans and mice. In this study, we set up a preclinical study to investigate the usefulness of a DNA vaccine producing mouse HSP105 whole protein for cancer immunotherapy in vivo using BALB/c and C57BL/6 mice, Colon26, a syngeneic endogenously HSP105-expressing colorectal cancer cell line, and B16.F10, a melanoma cell line. The DNA vaccine was used to stimulate HSP105-specific T-cell responses. Fifty percent of mice immunized with the HSP105 DNA vaccine completely suppressed the growth of subcutaneous Colon26 or B16.F10 cells accompanied by massive infiltration of both CD4+ T cells and CD8+ T cells into tumors. In cell transfer or depletion experiments we proved that both CD4+ T cells and CD8+ T cells induced by these vaccines play critical roles in the activation of antitumor immunity. Evidence of autoimmune reactions was not present in surviving mice that had rejected tumor cell challenges. We found that HSP105 was highly immunogenic in mice and that the HSP105 DNA vaccination induced antitumor immunity without causing autoimmunity. Therefore, HSP105 is an ideal tumor antigen that could be useful for immunotherapy or the prevention of various human tumors that overexpress HSP105, including colorectal cancer and melanoma.


Effect of bacterial meningitis complicating severe head trauma upon brain microdialysis and cerebral perfusion.
This article describes changes in regional cerebral perfusion and brain metabolism in a case of bacterial meningitis complicating severe traumatic brain injury. As part of clinical monitoring of patients with severe head injury, cerebral microdialysis was performed and extracellular concentration of glucose, lactate, glutamate, and pyruvate was determined. A thermal diffusion probe was used for bedside monitoring of cerebral blood flow. Acinetobacter meningitis complicated the clinical course on the seventh post-admission day and dramatically altered the neurochemistry. Microdialysate analysis showed glucose under the detection limit, lactate at moderately high levels, and a marked increase in glutamate and pyruvate levels. A reduction of cerebral perfusion was detected in the early phase of meningitis, probably secondary to vascular complications related to the inflammatory process. This case describes an emerging area of study and practice in patients with brain injury. It demonstrates how cerebral perfusion monitoring and study of brain metabolism can provide an early detection of secondary events that complicate severe head injury and can contribute to a better understanding of the complex pathogenetic mechanisms responsible for neuronal damage.


Citrate boosts the performance of phosphopeptide analysis by UPLC-ESI-MS/MS.
Incomplete recovery from the LC column is identified as a major cause for poor detection efficiency of phosphopeptides by LC-MS/MS. It is proposed that metal ions adsorbed on the stationary phase interact with the phosphate group of phosphopeptides via an ion-pairing mechanism related to IMAC (IMAC: immobilized metal ion affinity chromatography). This may result in their partial or even complete retention. Addition of phosphate, EDTA or citrate to the phosphopeptide sample was tested to overcome the detrimental phosphopeptide suppression during gradient LC-MS/MS analysis, while the standard solvent composition (water, acetonitrile, formic acid) of the LC system was left unchanged. With the use of UPLC, a citrate additive was found to be highly effective in increasing the phosphopeptide detection sensitivity. Addition of EDTA was found to be comparable with respect to sensitivity enhancement, but led to fast clogging and destruction of the spray needle and analytical columns due to precipitation. In contrast, a citrate additive is compatible with prolonged and stable routine operation. A 50 mM citrate additive was tested successfully for UPLC-MS analysis of a commercial four-component phosphopeptide mixture, a tryptic beta-casein digest, and several digests of the 140 kDa protein SETDB1. In this protein, 27 phosphorylation sites could be identified by UPLC-MS/MS using addition of citrate, including the detection of several phosphopeptides carrying 3-5 pSer/pThr residues, compared to identification of only 10 sites without citrate addition. A 50 mM citrate additive particularly increases the recovery of multiply phosphorylated peptides, thus, extending the scope of phosphopeptide analysis by LC-MS/MS.


Effect of amphotericin B on water and urea transport in the inner medullary collecting duct.
The clinical usefulness of amphotericin B (AMP-B) is limited by its nephrotoxicity, as characterized by decreased RPF, decreased GFR, impaired urinary acidification, and potassium excretion defects. Defects of renal concentrating ability have been noted, but the mechanisms responsible for them have not been investigated. The chief objective of this research was to analyze directly the effect of AMP-B on arginine-vasopressin (AVP)- or dibutyrl cAMP (DcAMP)-stimulated water and urea transport of the inner medullary collecting duct (IMCD) obtained from rats by the in vitro microperfusion technique. AMP-B (10(-5) M) added to the bath fluid in the absence of AVP did not impair the hydraulic conductivity (Lp) and the urea permeability (Pu) of rat IMCD. AMP-B (10(-5) M) added to the bath fluid decreased the AVP-stimulated Lp (x 10(-6) cm/s.atm) of rat IMCD from 19.41 +/- 2.19 to 10.00 +/- 1.39 (P < 0.001), and the reversibility of its action was observed during a third period when Lp increased to 19.80 +/- 2.19 (P < 0.001) after the initial conditions were restored. In addition, AMP-B reduced DcAMP-stimulated Lp from 20.95 +/- 1.75 to 10.52 +/- 0.71 (P < 0.01) in a reversible manner when the drug was withdrawn from the bath. AMP-B also decreased AVP-stimulated Pu (x 10(-5) cm/s) when added to the bath fluid from 36.60 +/- 2.05 to 29.88 +/- 1.36 (P < 0.001), and this effect was reversible after AMP-B was withdrawn from the bath (37.40 +/- 1.36; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Analysis of anxiety levels and attitudes of nursing students toward the nursing profession during the COVID-19 pandemic.
This study was conducted to analyze the anxiety levels and attitudes of nursing students for the nursing profession during the COVID-19 pandemic. Data collection forms were sent online to nursing students of three different state or foundation universities in Turkey. In all, 456 individuals who answered the data collection forms were included in the study. Study results revealed that the total average score for the "Attitude Scale for Nursing Profession" was 162 ± 15.6. The Professional characteristics subdimension score average was 80.64 ± 7.02. Furthermore, the state of choosing nursing profession subdimension score average was 50.05 ± 9.23, whereas the Attitude for the general status of nursing profession subdimension score average was 34.38 ± 2.97. Due to the pandemic, anxiety levels for the nursing profession were 4.86 ± 2.76 (between 0 and 10). It was determined that nursing students who studied in cities where the virus was very common had a more positive attitude toward the profession. Anxiety levels of nursing students studying in cities where the virus impact was moderate and in cities where the virus presence was quite common were higher (p > 0.05). PRACTICAL IMPLICATIONS: It was found that nursing students had a positive and high-level attitude toward the nursing profession. Furthermore, the results demonstrated that attitudes toward the nursing profession decreased significantly as anxiety increased.


Temporal and spatial expression of biglycan in chronic oxygen-induced lung injury.
To assess the temporal and spatial expression of the matrix-associated proteoglycan, biglycan, in a model of chronic hyperoxia-induced lung injury, changes in mRNA and protein were examined using Northern blot analyses and immunohistochemistry. Newborn rats were exposed to 85% or 100% oxygen for 6 and 4 wk, respectively. Exposure to 85% oxygen for up to 6 wk resulted in a reduction in lung surface area and the development of focal areas of fibrosis. In contrast, exposure to 100% oxygen resulted in gross alterations in lung histology with greatly enlarged airspaces and septal thickening. Biglycan mRNA increased at 3 to 5 wk in control animals, then returned to baseline, while oxygen-exposed animals showed a further increase after 2 to 4 wk of exposure. Immunoreactive biglycan decreased with postnatal age but increased in alveolar cells of animals exposed to 100% oxygen for 4 wk and in alveolar cells and along alveolar septae of animals exposed to 85% oxygen for 6 wk. We speculate that biglycan binds growth factors such as transforming growth factor-beta near these cells, acting in an autoregulatory fashion to support epithelial cell proliferation and inhibit mesenchymal cell proliferation.


[Effect of Pien Tze Huang against EV71].
This study aims to investigate the inhibitory effect of Pien Tze Huang(PZH) on enterovirus 71(EV71). To be speci-fic, chemiluminescence method was adopted to evaluate the toxicity of PZH to African green monkey kidney(Vero) cells and human rhabdomyosarcoma(RD) cells, and cytopathic effect(CPE) method to assess the inhibition on EV71-GFP reporter virus and EV71 C4 wild-type virus. The results showed that PZH had low cytotoxicity to Vero cells and RD cells, with the half-maximal cytotoxic concentration(CC_(50)) of about 0.691 3-0.879 2 mg·mL~(-1) for the two. In addition, PZH can effectively inhibit the replication of EV71 within the non-cytotoxic concentration range, and dose-dependently alleviate the cytopathic changes caused by virus infection, with the half-maximal effective concentration(EC_(50)) of 0.009 2-0.106 3 mg·mL~(-1). On the basis of the above results, the green fluorescent protein(GFP), indirect immunofluorescence assay(IFA), and median tissue culture infective dose(TCID_(50)) were employed to assess and verify the anti-EV71-GFP and anti-EV71 C4 activity of PZH. The results demonstrated that PZH can dose-dependently lower the expression of GFP by EV71-GFP and structural protein VP-1 by EV71 C4 and decrease the production of progeny infectious viruses. The EC_(50) of PZH for EV71-GFP and EV71 C4 was about 0.006 0-0.006 2 mg·mL~(-1) and 0.006 6-0.025 6 mg·mL~(-1), respectively. This study suggested that PZH may exert antiviral activity by acting on EV71 and interfering with the expression of VP-1. At the moment, there is still a lack of specific anti-EV71 drugs. This study proposed a new idea for the symptomatic treatment of EV71 infections such as hand-foot-mouth disease and verified an effective drug for the treatment of EV71 infections.


Clinical Implications of Novel Genomic Discoveries in Chronic Lymphocytic Leukemia.
Chronic lymphocytic leukemia (CLL) is a common B-cell malignancy with a remarkably heterogeneous course, ranging from indolent disease with no need for immediate therapy to rapidly progressive disease associated with therapeutic resistance. The recent US Food and Drug Administration approvals of novel targeted therapies such as inhibitors of B-cell receptor signaling and B-cell lymphoma 2 have opened up new opportunities in the clinical management of patients with CLL and heralded a new era in the clinical treatment of this disease. In parallel, the implementation of novel sequencing technologies has provided new insights into CLL complexity, identifying a growing list of putative drivers that underlie inter- and intratumor heterogeneities in CLL affecting disease progression and resistance. The identification of these novel genomic features that can indicate future drug resistance or guide therapeutic management is now becoming a major goal in CLL so that patients can best benefit from the increasingly diverse available therapies, as discussed herein.


Apoptotic DNA degradation: evidence for novel enzymes.
Apoptosis is characterized by multiple morphological and biochemical changes. One biochemical change that has been primarily associated with apoptosis is the cleavage of chromatin in the internucleosomal regions. We have taken two independent approaches to investigating the enzyme(s) responsible for such cleavage. First, using SDS-PAGE gels with (32)P-labelled DNA incorporated into the matrix, we identified a nuclease activity (termed NUC18) from apoptotic thymocytes. This enzyme has been purified to homogeneity and the activity of the pure protein is dependent on Ca(2+) and Mg(2+) while inhibited by Zn(2+) and aurintricarboxylic acid. This protein is found in the nucleus of apoptotic and nonapoptotic cells but is maintained in nondying cells in a large-molecular-weight inactive complex. NUC18 has a denatured molecular weight of 18 Kd but elutes from gel filtration columns with a native molecular weight of approximately 25 Kd. Although an exhaustive search has not been performed, NUC18 has been identified in several cell lines and tissues. Our second approach is designed specifically to detect internucleosomal cleavage of DNA, an obvious requirement for an apoptotic nuclease. By examining the degradation of HeLa chromatin, we have identified a low-molecular-weight of approximately 23 Kd native molecular weight) internucleosomal cleavage enzyme active in nuclear extracts from glucocorticoid-treated thymocytes. This activity is also dependent upon Ca(2+)and Mg(2+) and is inhibited by Zn(2+) as well as aurintricarboxylic acid. It is present in a variety of cell lines and tissues and is maintained in control cells in a latent state prior to apoptosis. In addition to similarities in physical properties, the two enzymes appear to be immunologically related to one another by virtue of their ability to interact with the same antibody. Overall, using independent approaches, we have identified two nucleases with similar biochemical properties whose activity correlates with apoptosis. The current work suggests that these are novel and perhaps closely related enzymes.


Visible-light Induced Reduction of Graphene Oxide Using Plasmonic Nanoparticle.
Present work demonstrates the simple, chemical free, fast, and energy efficient method to produce reduced graphene oxide (r-GO) solution at RT using visible light irradiation with plasmonic nanoparticles. The plasmonic nanoparticle is used to improve the reduction efficiency of GO. It only takes 30 min at RT by illuminating the solutions with Xe-lamp, the r-GO solutions can be obtained by completely removing gold nanoparticles through simple centrifugation step. The spherical gold nanoparticles (AuNPs) as compared to the other nanostructures is the most suitable plasmonic nanostructure for r-GO preparation. The reduced graphene oxide prepared using visible light and AuNPs was equally qualitative as chemically reduced graphene oxide, which was supported by various analytical techniques such as UV-Vis spectroscopy, Raman spectroscopy, powder XRD and XPS. The reduced graphene oxide prepared with visible light shows excellent quenching properties over the fluorescent molecules modified on ssDNA and excellent fluorescence recovery for target DNA detection. The r-GO prepared by recycled AuNPs is found to be of same quality with that of chemically reduced r-GO. The use of visible light with plasmonic nanoparticle demonstrates the good alternative method for r-GO synthesis.


Phase distribution analysis of tissues based on the off-axis digital holographic hybrid reconstruction algorithm.
Off-axis digital holography (DH) has great potential in histopathology for its high efficiency and precision. Phase distribution, usually extracted by the angular spectrum (AS) algorithm from a digital hologram, reflects important structural information of biological tissues. However, the complex structure of tissues introduces spectrum aliasing of the hologram, making the AS algorithm hard to realize and accurate phase analysis difficult to conduct. Here, we present a hybrid reconstruction algorithm, combining Fresnel reconstruction in spatial domain with the AS algorithm in frequency domain, to solve aliasing by spatial filtering. Through simulation, we demonstrate the feasibility and superiority of the hybrid algorithm and verified the precision (10-3 rad) of the hybrid algorithm with spectrum aliasing. We extract phase distributions from normal urothelial and bladder cancer tissues by the hybrid algorithm and make quantitative analysis through histogram and standard deviation. The result shows the hybrid algorithm in off-axis DH has great advantage for the high-precision phase extraction of tissues and supplies significant information for cancer diagnosis.


Blood culture of the canine patient.
Blood for bacteriologic culture was obtained from 581 sick dogs. Of these, 134 (23%) were considered to have bacteremia. The conditions most frequently associated with bacteremia were malignant neoplasms and infections of the skeletal, cardiovascular, and urogenital systems. The most frequently isolated bacteria were members of the family Enterobacteriaceae and coagulase-positive staphylococci, in sum accounting for more than 50% of the 150 isolates. Most of the dogs with bacteremia had high proportions of immature neutrophils, segmented neutrophils, and monocytes in blood. Dogs with bacteremia and osteomyelitis due to staphylococci had normal hemograms. Blood from dogs with bacteremia due to gram-negative bacteria was more likely to have a high proportion of immature and segmented neutrophil leukocytes than was blood from dogs with bacteremia due to a gram-positive species. Toxic neutrophils were observed more often in blood obtained from patients with bacteremia due to gram-negative bacteria. The development of fever correlated with the bacteremic state regardless of the species of bacteria in the blood.


[Current trends in nutrigenomics of obesity].
One of the most general chronic illness in the world is obesity, which lead to progression of cardiovascular diseases, diabetes mellitus type 2, metabolic syndrome and other diseases. Slow body weight gain, that leads to overweight, is a long-term aftereffect of a long-term positive energy balance, which occurs as a result of physical activity reduction and calorie intake increasing. Trend in the reduction of physical activity and increasing the caloric value of food intake is probably the main reason of increasing patients with obesity, but it's necessary to mention that this tendency occurs because of genetic variation in population. The volume of scientific information, relevant to the problem of genetic predisposition testing to obesity, is highly increasing. This article provides an overview of recent data on the genetics of obesity and the role of genetic testing of candidate genes polymorphisms, as well as genes associated with carbohydrate and lipid metabolism disorders (FTO, ADRB2, ADRB3, PPARG and a number of others). The role of nutrigenomics in personalization of diet treatment for obesity.


B7-H4 expression is correlated with tumor progression and clinical outcome in urothelial cell carcinoma.
To investigate the mRNA and protein levels of B7-H4, a B7 family molecule, in human urothelial cell carcinoma (UCC), to analyze the relationship between B7-H4 protein expression level and pathological stage of UCC, and to examine the potential of B7-H4 as a prognostic factor in UCC. mRNA and protein levels of B7-H4 were measured in pairs of tumor tissues and matched adjacent nontumor tissue obtained from patients with UCC by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemical staining, respectively. Association of the protein level of B7-H4 with pathological tumor stage and the overall survival of UCC patients were also analyzed. B7-H4 mRNA and protein level were significantly higher in UCC tumor tissues compared with adjacent nontumor tissues as assessed by qRT-PCR and immunohistochemical staining, respectively. Higher B7-H4 protein levels were observed in patients with more advanced pathological stage of UCC and were also associated with decreased overall survival of patients with UCC. The findings from this study indicate that B7-H4 has the potential to be an independent prognostic indicator for UCC.


The fakability of subtle and obvious measures of aggression by male prisoners.
Fifty-eight adult male felons were given the Minnesota Multiphasic Personality Inventory (MMPI), the Buss - Durkee Hostility Inventory ( BDHI ), and the Draw-a-Person Test (DAP) to test the relative sensitivity of subtlety or obviousness of items to response sets. The inmates were randomly assigned to three response set groups: a fake-aggressive group, a fake-nonaggressive group, and a standard-instruction control group. The MMPIs were scored for five obvious and five subtle aggression or hostility research scales. The BDHI is a totally obvious test, whereas the DAP is a very subtle measure. A paradoxical relationship between response set and subtlety of the scales was hypothesized, such that the obvious scales could be successfully faked , but the subtle scales would show scores in the opposite from the intended direction. It was found that the inmates did correctly manipulate the obvious scales, but the subtle scales did not consistently show the hypothesized trend. Possible reasons for this are discussed, including the nature of the scales used and characteristics of the population.


In vitro adsorption study of fluoxetine onto activated charcoal at gastric and intestinal pH using high performance liquid chromatography with fluorescence detector.
This in vitro investigation was performed to study the adsorption characteristics of fluoxetine to activated charcoal and its commercial formulation Carbomix powder in simulated gastric (pH = 1.2) and intestinal (pH = 7.2) fluid environments. Solutions containing fluoxetine and charcoal were incubated at 37 degrees C for one hour. Reversed phase high performance liquid chromatography was used for the determination of free fluoxetine concentrations (range 0.2-8 micrograms/mL) in the diluted filtrate. The maximum adsorption capacities at pH 1.2 for activated charcoal and Carbomix were 223 and 333 mg/g, respectively; at pH 7.2 they were 301 and 453 mg/g, respectively. The affinity constant values at pH 1.2 of activated charcoal and Carbomix were 441 and 122 L/g, respectively, while at pH 7.2 they were 482 and 589 L/g, respectively, indicating a strong binding of fluoxetine onto charcoals. Relative to the toxic and lethal doses in cases of fluoxetine intoxications, both types of charcoals tested were found effective for adsorption at gastric and intestinal pH. Adsorbed fluoxetine was significantly increased at intestinal pH, consistent with predominant adsorption of the undissociated form of the drug. We conclude that activated charcoal and Carbomix have adsorptive properties appropriate to medical treatment in cases of fluoxetine overdose.


Cortical and subcortical functional specificity associated with response inhibition.
Is motor response inhibition supported by a specialised neuronal inhibitory control mechanism, or by a more general system of action updating? This pre-registered study employed a context-cueing paradigm requiring both inhibitory and non-inhibitory action updating in combination with functional magnetic resonance imaging to test the specificity of responses under different updating conditions, including the cancellation of actions. Cortical regions of activity were found to be common to multiple forms of action updating. However, functional specificity during response inhibition was observed in the anterior right inferior frontal gyrus. In addition, fronto-subcortical activity was explored using a novel contrast method. These exploratory results indicate that the specificity for response inhibition observed in right prefrontal cortex continued downstream and was observed in right hemisphere subcortical activity, while left hemisphere activity was associated with right-hand response execution. Overall, our findings reveal both common and distinct correlates of response inhibition in prefrontal cortex, with exploratory analyses supporting putative models of subcortical pathways and extending them through the demonstration of lateralisation.


Pilot study of menopause symptoms in a clinic population.
Studies analyzing menopause symptoms have primarily focused on white women of higher socioeconomic status. With an aging population and a longer life expectancy, we can anticipate a significant rise in women presenting with menopause symptoms and issues related to quality of life. It is important to know whether current data regarding menopause symptoms are applicable to all women seeking care. Data from the first 80 consecutive women, predominantly Hispanic and of lower socioeconomic status, presenting to the Women's Life Center at Hartford Hospital were analyzed for demographic and socioeconomic variables, depression, factors related to quality of life, and menopause symptoms. Although hot flashes (63.8%) and night sweats (55.1%) occurred at a frequency similar to that reported in the literature, mood swings (77.9%), decrease in energy (75.9%), sleeping problems (73.4%), and memory problems (67.1%) were the four most common symptoms. Although there were many symptoms that could impact negatively on their quality of life, 82.3% felt that it was wonderful to be alive during menopause, 73% were satisfied with their life, and the cumulative depression score did not fall into the depressed category. This sample of predominantly Hispanic women of lower socioeconomic status experienced negative quality-of-life-related symptoms at a much higher frequency than has been previously reported. The menopause years, although feared by many, can be a wonderful time in a woman's life. Whether the differences identified are due to ethnicity, socioeconomic factors, or a combination of the two has yet to be determined.


Dependence on growth phase and temperature of the composition of a nitrogen-fixing cyanobacterium.
The effects of growth phase and temperature on the molecular and elemental composition of Anabaena variabilis cells grown under nitrogen-fixing conditions have been studied in batch cultures. Irrespective of the growth temperature, this cyanobacterium underwent a gradual increase in its protein and lipid contents in the transition from exponential to deceleration phase that was accompanied by a parallel decrease in carbohydrates and nucleic acids. Also in response to this, transition increases in carbon, nitrogen, and hydrogen contents with a concomitant decline in oxygen content was a common pattern for all growth temperatures tested. Whereas temperature rise did not affect significantly the protein and carbohydrate contents in exponentially growing cells, for cells in the deceleration phase proteins declined and carbohydrates increased with increasing temperature. From growth and elemental composition data several bioenergetic parameters were derived for A. variabilis cells. Both aging of cultures and rise in temperature resulted in increases of both biomass degree of reduction and heat of combustion. Nevertheless, biomass energetic yield was only slightly affected by variations in growth temperature and the maintenance coefficient was virtually constant within the range of temperatures tested.


Effects of verapamil on accessory pathway properties and induction of circus movement tachycardia in patients with the Wolf-Parkinson-White syndrome.
The electrophysiological effects of 0.2 mg/kg of intravenously administered verapamil (mean plasma level, 51.3 ng/ml) were evaluated using intracardiac recordings and electrical stimulation in 10 patients with the concealed or manifest Wolff-Parkinson-White syndrome. Verapamil produced a minimal effect on both the antegrade and retrograde effective refractory periods of the accessory pathway and the retrograde conduction time over the accessory pathway, but significantly lengthened the intranodal conduction time as well as the effective and functional refractory periods of the atrioventricular (AV) node. Reproducible sustained circus movement tachycardia was initiated in 8 patients before administration of verapamil and in 2 after verapamil. The sustained tachycardia could no longer be initiated in 6 patients because of an increase in AV nodal refractoriness. In 4 patients, atrial echoes were induced at longer premature beat intervals due to a greater AV conduction delay of the atrial impulse. The cycle length of the tachycardia was lengthened in 2 patients, reflecting an increase in the A-H interval after verapamil administration. In conclusion, these results show that verapamil has no apparent effect on either antegrade or retrograde accessory pathway properties and suggest that verapamil does indeed prevent sustained circus movement tachycardia by increasing the AV nodal refractoriness in some patients with the Wolff-Parkinson-White syndrome.


Correlates of self-harm in university students: A cross-sectional study.
Objective: To determine the prevalence of university students who have ever engaged in self-harm and to examine its correlates. Frequency of thinking about self-harm was explored as a secondary outcome. Participants: Students at Western University in London, Ontario, Canada. Methods: This cross-sectional study was completed via an online questionnaire. Logistic regressions assessed the influence of sociodemographic and behavioral factors associated with lifetime self-harm and thoughts about self-harm. Results: The sample consisted of 2626 university students. Almost 25% engaged in self-harm in their lifetime and close to 33% have thought about harming themselves. A non-straight sexual orientation, marijuana use, prescription drugs not prescribed, and mental health problems increased the risk of both outcomes. Females were over two times more likely to engage in self-harm than males. Conclusion: This study provides evidence that is needed for developing effective interventions to reduce the risk of self-harm by targeting university students who are most at-risk.


[Main results of the Biorisk experiment on the International Space Station].
To get better appreciation of the margins of phenotypic adaptation and genotypic changes in bacteria-fungi associations within the typical microbiota residing on structural materials of space-flown equipment, developed were a program and hardware for a series of experiments under the general name BIORISK. Protocol of each experimental cycle is based on the well-proven method of exposure of "passive" samples of materials (Biorisk-KM), microorganisms-materials systems inside the ISS service module (Biorisk-MSV), and microorganisms-materials systems on the outside of the ISS SM (Biorisk-MSN). Each six months the samples are returned to the laboratory in conjunction with crew rotation. Already the first in-hand data from the experiment point to the dramatic effect of space flight on growth, reproduction, and biological properties of test microbes and fungi. Thus, the activity of enzymes that characterize the pathogenic potential (RNA-ase and DNA-ase), and resistance of microorganisms to aseptic agents were found increased.


Management of prostate cancer in the older man.
Due to the high incidence and prevalence in older men, prostate cancer is best understood as an age-associated disease. Physicians and their older patients commonly face the dilemma of whether or not to initiate treatment for localized disease or early systemic relapse (ie, biochemical recurrence). Although many older men with symptomatic advanced prostate cancer benefit from hormonal treatments and chemotherapies, treatment complications also may influence outcome. Older prostate cancer patients have a high prevalence of other factors that can limit remaining life expectancy (RLE), quality of life (QOL), and tolerance to treatment. A comprehensive geriatric assessment (CGA) can help identify other health status issues that can predict morbidity or mortality in vulnerable or frail older prostate cancer populations. Despite a growing body of evidence, more research is needed to establish optimal treatment strategies for all disease stages in prostate cancer patients diagnosed later in life.


Whole Blood ω-3 Fatty Acids Are Inversely Associated with Carotid Intima-Media Thickness in Indigenous Mexican Women.
Long-chain ω-3 (n-3) polyunsaturated fatty acids (PUFAs) may reduce the risk of atherosclerosis. The association between n-3 PUFAs and cardiovascular disease may vary across different populations, and there is limited information on Hispanic individuals with mixed Amerindian and European origin. We evaluated the cross-sectional relations between whole blood n-3 PUFAs and carotid intima-media thickness (IMT) in Mexican women living in Mexico and assessed whether this relation was different in women who spoke an indigenous language compared with women who did not. In 2012-2013, we assessed the association between blood n-3 PUFAs and IMT in 1306 women free of disease in Chiapas and Yucatan, Mexico. We categorized blood n-3 PUFAs (% of total FAs) in quartiles and adjusted linear regression models by age, indigenous language, site, socioeconomic status, education, smoking, menopause, diabetes, hypertension, hypercholesterolemia, body mass index, physical activity, and diet. We stratified analyses by indigenous/nonindigenous language speakers (n = 315 of 991). Whole blood n-3 PUFAs (means ± SDs) were 3.58% ± 0.78% of total FAs. We did not observe a significant association between n-3 PUFAs and IMT in the overall study population. However, the adjusted mean difference of IMT was -6.5% (95% CI: -10.7%, -2.3%; P-trend < 0.0001) for indigenous women in the highest quartile compared with the lowest quartile of blood n-3 PUFAs. In nonindigenous women, we did not observe an association (-0.6%; 95% CI: -3.0%, 1.8%, comparing extreme quartiles; P-trend = 1.00). Overall, circulating n-3 PUFAs were not associated with IMT. However, we observed a strong statistically significant inverse association with IMT in indigenous Mexican women. Future studies should evaluate genetic markers that may reflect differences in n-3 PUFA metabolism across populations.


Control time reduction using virtual source projection for treating a leg sarcoma with nonlinear perfusion.
Blood perfusion is a well-known factor that complicates accurate control of heating during hyperthermia treatments of cancer. Since blood perfusion varies as a function of time, temperature and location, determination of appropriate power deposition pattern from multiple antenna array Hyperthermia systems and heterogeneous tissues is a difficult control problem. Therefore, we investigate the applicability of a real-time eigenvalue model reduction (virtual source - VS) reduced-order controller for hyperthermic treatments of tissue with nonlinearly varying perfusion. We impose a piecewise linear approximation to a set of heat pulses, each consisting of a 1-min heat-up, followed by a 2-min cool-down. The controller is designed for feedback from magnetic resonance temperature images (MRTI) obtained after each iteration of heat pulses to adjust the projected optimal setting of antenna phase and magnitude for selective tumor heating. Simulated temperature patterns with additive Gaussian noise with a standard deviation of 1.0°C and zero mean were used as a surrogate for MRTI. Robustness tests were conducted numerically for a patient's right leg placed at the middle of a water bolus surrounded by a 10-antenna applicator driven at 150 MHz. Robustness tests included added discrepancies in perfusion, electrical and thermal properties, and patient model simplifications. The controller improved selective tumor heating after an average of 4-9 iterative adjustments of power and phase, and fulfilled satisfactory therapeutic outcomes with approximately 75% of tumor volumes heated to temperatures >43°C while maintaining about 93% of healthy tissue volume < 41°C. Adequate sarcoma heating was realized by using only 2 to 3 VSs rather than a much larger number of control signals for all 10 antennas, which reduced the convergence time to only 4 to 9% of the original value. Using a piecewise linear approximation to a set of heat pulses in a VS reduced-order controller, the proposed algorithm greatly improves the efficiency of hyperthermic treatment of leg sarcomas while accommodating practical nonlinear variation of tissue properties such as perfusion.


More than a Virulence Factor: Patulin Is a Non-Host-Specific Toxin that Inhibits Postharvest Phytopathogens and Requires Efflux for Penicillium Tolerance.
Mycotoxin contamination is a leading cause of food spoilage and waste on a global scale. Patulin, a mycotoxin produced by Penicillium spp. during postharvest pome fruit decay, causes acute and chronic effects in humans, withstands pasteurization, and is not eliminated by fermentation. While much is known about the impact of patulin on human health, there are significant knowledge gaps concerning the effect of patulin during postharvest fruit-pathogen interactions. Application of patulin on six apple cultivars reproduced some blue mold symptoms that were cultivar-independent and dose-dependent. Identical symptoms were also observed in pear and mandarin orange. Six Penicillium isolates exposed to exogenous patulin exhibited delayed germination after 24 h, yet all produced viable colonies in 7 days. However, four common postharvest phytopathogenic fungi were completely inhibited by patulin during conidial germination and growth, suggesting the toxin is important for Penicillium to dominate the postharvest niche. Using clorgyline, a broad-spectrum efflux pump inhibitor, we demonstrated that efflux plays a role in Penicillium auto-resistance to patulin during conidial germination. The work presented here contributes new knowledge of patulin auto-resistance, its mode of action, and inhibitory role in fungal-fungal interactions. Our findings provide a solid foundation to develop toxin and decay mitigation approaches.


Extraction, purification, characterization and antioxidant activities of polysaccharides from Ramaria botrytis (Pers.) Ricken.
Ramaria botrytis (Pers.) Ricken, a member of the family Clavariaceae, has been widely prescribed for anti-aging and improving immunity. To extract and purify the polysaccharides, the main constituent of the fruiting-body, from R. botrytis and explore antioxidant activities was great significant. Ramaria botrytis polysaccharides (RBP) was extracted with water at 88.47 °C for 1.42 h with a solution to sample ratio of 10.94 mL g-1 employing response surface methodology. Four purified fractions, RBP-1, RBP-2, RBP-3, and RBP-4, were obtained from column chromatography of DEAE-52 and Sephadex G-100. Among these four purified fractions, RBP-1, RBP-2, RBP-4 were mainly composed of glucose, while RBP-3 contained 41.36% mannose and 28.96% glucose. The molecular weights of RBP-1, RBP-2, RBP-3 and RBP-4 were 6.48, 36.12, 96.72 and 8.34 kDa, respectively. These four fractions are also tested for antioxidant activities in vitro, RBP-4 exhibited strong assay of reducing power and high scavenging activity on DPPH radical, while RBP-3 showed the stronger ability of hydroxyl radical scavenging activity. Response surface methodology was successfully applied to optimize the ultrasonic extraction of polysaccharides from R. botrytis. RBP is an efficient natural antioxidant.


Helping parents support their child in pain.
Children who are experiencing pain in health care settings require the supportive presence of a parent to help them cope effectively. In fact, 99% of children state that "having their parent" present provides the most comfort when in pain. Yet, parents are often excluded from providing this support. Health professionals often encourage parents to "wait outside" until a procedure is over, believing that this facilitates the child's cooperation, especially for more invasive procedures. In fact, parents can use a variety of comforting and distracting strategies to support their child during a painful procedure. This manuscript presents research findings about parents' and health care professionals' attitudes and practices related to children in pain. Finally, strategies are presented for nurses to use in assisting parents who want to support their child during a painful experience.


Macular hole formation in a patient with Irvine-Gass syndrome: coincidence or rare complication?
Macular edema (ME) is caused by abnormal retinal capillary permeability and has also been described as a postoperative complication of cataract surgery (Irvine-Gass syndrome). To present a patient with Irvine-Gass syndrome in the right eye complicated with a macular hole (MH) in the same eye and possible associations between these two entities. A 72-year-old male with a history of uneventful bilateral cataract surgery was followed-up with biomicroscopy and optical coherence tomography (OCT). Four weeks after cataract surgery oculus dexter (OD), there was progressive visual deterioration (best corrected visual acuity [BCVA]: 0.5). OCT disclosed cystoid ME. A parabulbar triamcinolone injection, dexamethasone 0.1% and ketorolac 0.4% eye drops, both 4 times per day OD were administered. Six weeks later (BCVA OD: 0.2), OCT revealed cystoid ME and full-thickness MH. ME secondary to diabetes or central retinal vein occlusion may lead to MH by inducing focal vitreomacular traction and by triggering inflammatory mechanisms which facilitate a marked thinning of the fovea. MH may occur even in cases of pseudophakic ME, representing a rare complication of Irvine-Gass syndrome.


Phase 2 Trial of Oncolytic H-1 Parvovirus Therapy Shows Safety and Signs of Immune System Activation in Patients With Metastatic Pancreatic Ductal Adenocarcinoma.
To investigate the safety, clinical efficacy, virus pharmacokinetics, shedding, and immune response after administration of an oncolytic parvovirus (H-1PV, ParvOryx) to patients with metastatic pancreatic ductal adenocarcinoma (PDAC) refractory to first-line therapy. This is a noncontrolled, single-arm, open-label, dose-escalating, single-center clinical trial. Seven patients with PDAC and at least one liver metastasis were included. ParvOryx was administered intravenously on 4 consecutive days and as an intralesional injection, 6 to 13 days thereafter. Altogether, three escalating dose levels were investigated. In addition, gemcitabine treatment was initiated on day 28. ParvOryx showed excellent tolerability with no dose-limiting toxicities. One patient had a confirmed partial response and one patient revealed an unconfirmed partial response according to RECIST criteria. Both patients showed remarkably long surivial of 326 and 555 days, respectively. Investigation of pharmacokinetics and virus shedding revealed dose dependency with no excretion of active virus particles in saliva or urine and very limited excretion in feces. H-1PV nucleic acids were detected in tumor samples of four patients. All patients showed T-cell responses to viral proteins. An interesting immunologic pattern developed in tumor tissues and in blood of both patients with partial response suggesting immune activation after administration of ParvOryx. The trial met all primary objectives, revealed no environmental risks, and indicated favorable immune modulation after administration of ParvOryx. It can be considered a good basis for further systematic clinical development alone or in combination with immunomodulatory compounds.


Asymmetric synthesis of 3-hydroxy-pyrrolidines via tin-lithium exchange and cyclization.
We report a method for the synthesis of chiral pyrrolidines using tin-lithium exchange and cyclization reactions. The precursors are formed readily from simple starting materials and undergo tin-lithium exchange by treatment with n-butyllithium. Subsequent intramolecular carbolithiation is stereoselective to give highly enantiomerically enriched pyrrolidines in excellent yields.


Exploring the role of hydration and confinement in the aggregation of amyloidogenic peptides Aβ(16-22) and Sup35(7-13) in AOT reverse micelles.
Knowledge of how intermolecular interactions of amyloid-forming proteins cause protein aggregation and how those interactions are affected by sequence and solution conditions is essential to our understanding of the onset of many degenerative diseases. Of particular interest is the aggregation of the amyloid-β (Aβ) peptide, linked to Alzheimer's disease, and the aggregation of the Sup35 yeast prion peptide, which resembles the mammalian prion protein linked to spongiform encephalopathies. To facilitate the study of these important peptides, experimentalists have identified small peptide congeners of the full-length proteins that exhibit amyloidogenic behavior, including the KLVFFAE sub-sequence, Aβ16-22, and the GNNQQNY subsequence, Sup357-13. In this study, molecular dynamics simulations were used to examine these peptide fragments encapsulated in reverse micelles (RMs) in order to identify the fundamental principles that govern how sequence and solution environment influence peptide aggregation. Aβ16-22 and Sup357-13 are observed to organize into anti-parallel and parallel β-sheet arrangements. Confinement in the sodium bis(2-ethylhexyl) sulfosuccinate (AOT) reverse micelles is shown to stabilize extended peptide conformations and enhance peptide aggregation. Substantial fluctuations in the reverse micelle shape are observed, in agreement with earlier studies. Shape fluctuations are found to facilitate peptide solvation through interactions between the peptide and AOT surfactant, including direct interaction between non-polar peptide residues and the aliphatic surfactant tails. Computed amide I IR spectra are compared with experimental spectra and found to reflect changes in the peptide structures induced by confinement in the RM environment. Furthermore, examination of the rotational anisotropy decay of water in the RM demonstrates that the water dynamics are sensitive to the presence of peptide as well as the peptide sequence. Overall, our results demonstrate that the RM is a complex confining environment where substantial direct interaction between the surfactant and peptides plays an important role in determining the resulting ensemble of peptide conformations. By extension the results suggest that similarly complex sequence-dependent interactions may determine conformational ensembles of amyloid-forming peptides in a cellular environment.


Anterior pituitary cells express pattern recognition receptors for fungal glucans: implications for neuroendocrine immune involvement in response to fungal infections.
Hormones and cytokines are known to act as regulatory messengers between the neuroendocrine and immune systems. The innate immune system identifies infectious agents by means of pattern-recognition receptors. These receptors recognize pathogen-specific macromolecules called pathogen-associated molecular patterns. Fungal cell wall glucans nonspecifically stimulate various aspects of innate immunity via interaction with membrane receptors on immune-competent cells. Glucans are also released into the systemic circulation of patients with fungal infections. Recent evidence confirms the existence of glucan-specific receptors on cells outside the immune system. We hypothesized that glucans may directly interact with pituitary cells as an early signaling event in fungal infections. We characterized the receptor-mediated interaction of glucan derived from Candida albicans with pituitary cells using surface plasmon resonance. Prolactin levels were assayed by commercial ELISA. TLR2, TLR4 and CD14 mRNA levels were assessed by RT-PCR. A single glucan-specific binding site was identified on rodent somatomammotroph (K(D) = 3.9 microM) and human folliculostellate cell (K(D) = 3.6 microM) membranes. Coincubation of glucan with somatomammotroph cells for 72 h significantly (p < 0.01) increased prolactin accumulation by 56-62% over that observed in cells treated with media alone. Glucan also increased TLR4 and CD14 gene expression in human folliculostellate cells. Pituitary cells directly recognize and respond to fungal cell wall glucans resulting in stimulation of pituitary cell TLR4 and CD14 gene expression. In addition, glucan stimulates secretion of prolactin, a hormone that plays an important role in the response to infection.


Improving Thoracic Surgery Ward Round Quality and Enhancing Patient Safety in a Referral Centre.
Introduction Ward rounds are vital clinical processes that facilitate an opportunity for daily review and management of thoracic surgery inpatients. The aim of this study was to compare thoracic surgery ward round documentation against locally agreed standards and design a template to improve the detail and uniformity of this process to enhance patient care. Materials and methods Data for this audit was collected retrospectively and prospectively. Data was collected during three auditing periods and managed on Microsoft Excel. Descriptive statistics were used for its analysis. Chi-square and Fisher's Exact tests were used to test for differences in reporting rates. Results and discussion Initially, a total of 199 ward round notes were reviewed. Imaging results (19%) and discharge planning (23%) were not reported. eCARE (electronic Clinical Assessment for Round Evaluation) was developed to ensure that all aspects of patient evaluation recommended by the guidelines were included. Reporting rates significantly improved after such changes. We analysed the effect of the new ward round note on discharge planning (23.3 vs 41%, p<0.001), complication rates (32.6 vs 21.9%, p=0.03), post-surgical length of stay (LOS) (7.0 vs 5.0, p<0.001). Conclusion Over a year, we audited the Thoracic Surgery Department's ward round documentation against locally agreed standards in line with national recommendations. Several important items were not regularly reported. Using closed-ended questions improved reporting rates, and patient care was optimised. Further research should explore the impact of this new documentation method on patient care and postoperative outcomes in our Trust as well as other cardiothoracic centres.


Age-related changes in skeletal muscle composition: A pilot nuclear magnetic resonance spectroscopy study in mice.
The composition of skeletal muscle was investigated in the quadriceps and gastrocnemius muscle of 13-month-old (n=15) and 23-month-old (n=19) mice by means of high-resolution nuclear magnetic resonance (NMR) spectroscopy. Muscle specimens were dissected out, frozen in liquid nitrogen and extracted in chloroform/methanol, and proton NMR spectra of the resulting aqueous and organic fractions were obtained at 600MHz. Several metabolites were unambiguously identified and quantified. Multivariate ANOVA (factor: age, muscle, age×muscle) showed a significant main effect of age (P=0.031) on the amount of muscle metabolites, suggesting that the aging process affects the composition of skeletal muscle. Univariate tests showed significant differences for lactate, acetate, taurine, and uridine in 13- and 23-month-old mice. A trend for the effect of muscle (quadriceps vs. gastrocnemius; P=0.128) was also found. No significant muscle x age interaction was present. When the same data were used in principal component analysis, the first two principal components separated muscles (quadriceps and gastrocnemius) and ages (13- and 23-month-old), explaining 66.7% of total variance. The results of this pilot study show that high-resolution NMR spectroscopy is able to detect age-associated changes in skeletal muscle metabolites, thereby paving the way to future detailed metabolomics investigation in sarcopenia of aging.


Stable nitrogen and carbon isotopes in sediments and biota from three tropical marine food webs: Application to chemical bioaccumulation assessment.
Studies of trophodynamics and contaminant bioaccumulation in tropical marine ecosystems are limited. The present study employed stable isotope and trace contaminant analysis to assess sources of primary productivity, trophic interactions, and chemical bioaccumulation behavior in 2 mangrove food webs and 1 offshore coastal marine food web in Singapore. Samples of sediment, phytoplankton, mangrove leaves, clams, snails, crabs, worms, prawns, and fishes were analyzed for stable carbon and nitrogen isotope values, as well as concentrations of persistent organic pollutants. In the mangrove food webs, consumers exhibited similar δ13 C values, probably because of the well-mixed nature of these systems. However, the 2 primary consumers (common nerite and rodong snail) exhibited distinct δ13 C values (-21.6‰ vs -17.7‰), indicating different carbon sources. Fish from Singapore Strait exhibited similar δ13 C values, indicating common carbon sources in this offshore marine food web. The highest trophic level was found in glass perchlet (trophic level = 3.3) and tilapia (trophic level = 3.4) in the 2 mangrove food webs and grunter (trophic level = 3.7) in the Singapore Strait food web. Concentrations of polychlorinated biphenyl (PCB 153) and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) concentrations ranged from 0.9 to 84.6 ng/g lipid weight and from <0.2 to 267.4 ng/g lipid weight, respectively. The trophic magnification factors of PCB 153 and p,p'-DDE ranged between 1.63 and 4.62, indicating biomagnification in these tropical marine food webs. The findings provide important information that will aid future chemical bioaccumulation assessment initiatives. Environ Toxicol Chem 2017;36:2521-2532. © 2017 SETAC.


Purification of Rts1 RepA protein and binding of the protein to mini-Rts1 DNA.
RepA protein, essential for the replication of plasmid Rts1, was purified, and its binding to mini-Rts1 subregions was examined by a DNase I protection assay. RepA protected the incI and incII iterons, a region immediately upstream of the repA promoter, and a 10-base-pair region located between the most external incII iteron and a GATC box. The protection was less efficient when preheated RepA was used.


Induction of the mitogen-activated protein kinase phosphatase MKP3 by nerve growth factor in differentiating PC12.
In PC12 sympathetic neurons activation and nuclear translocation of ERK family MAP kinases plays an essential role in processes underlying nerve growth factor (NGF)-dependent differentiation. We have recently cloned MKP-3 as a novel dual specificity phosphatase displaying selectivity towards inactivation of the ERK1 and ERK2 MAP kinases. Here we report that in PC12 cells, MKP-3 undergoes powerful and specific up-regulation by NGF while a number of mitogens and cellular stresses are ineffective. NGF-stimulated MKP-3 expression appears after 1 h, is maximal at 3 h, and is sustained for 5 days. This coincides with a critical period of neurite outgrowth and terminal differentiation. Consistent with a role mediating inhibition of PC12 cell MAP kinases, NGF-stimulated ERK2 activation was suppressed considerably following pretreatment with fibroblast growth factor and 9-cis-retinal, two additional differentiation factors found to induce powerfully MKP-3 expression. Given the clear cytosolic localization of MKP3 in PC12 cells and sympathetic neurons, these results suggest a critical role for inactivating ERK MAP kinases in non-nuclear compartments during essential stages of NGF-mediated PC12 differentiation.


Synergetic spin singlet-quintet switching and luminescence in mononuclear Fe(II) 1,3,4-oxadiazole tetradentate chelates with NCBH3 co-ligand.
We report the multi-step synthesis of the tetradentate 2-(naphthalen-2-yl)-5-[N,N-bis(2-pyridylmethyl)aminomethyl]-1,3,4-oxadiazole ligand (LTetra-ODA) along with its corresponding [FeII(LTetra-ODA)(NCBH3)2]·1.5CH3OH (C1) complex, which is the first mononuclear 1,3,4-oxadiazole based Fe(II) spin crossover (SCO) complex, and its zinc analogue [ZnII(LTetra-ODA)(NCBH3)2]·0.5H2O (C2). The spin transition is followed by variable temperature (VT-) X-ray crystallography of [Fe(LTetra-ODA)(NCBH3)2]·1.5CH3OH (C1) at 120 and 220 K. The magnetic susceptibility measurements on the bulk sample recorded from 2 to 300 K show that the complex exhibits a complete abrupt reversible spin transition with a T1/2 of 207 K. The loss of the lattice solvent methanol shifts the T1/2 slightly to around 210 K. The spin transition in solution for [Fe(LTetra-ODA)(NCBH3)2]·1.5CH3OH (C1) was followed using the VT-1H-NMR Evans method in CD3CN, with a T1/2 of 357 K. Solid state VT luminescence studies provide some preliminary evidence of interplay of luminescence and spin transition in the [Fe(LTetra-ODA)(NCBH3)2]·1.5CH3OH (C1) complex.


[Comparison of continuous and discontinuous density gradient centrifugation for purification of human pancreatic islets].
To compare the effect of continuous and discontinuous density gradient centrifugation for purification of human pancreatic islets with COBE 2991 cell processor. Human pancreases were obtained from brain-dead donors and stored in cold UW solution. The connective tissues were removed from the pancreases, and the pancreatic ducts were perfused with a cold enzyme (Liberase). The islets were then separated by gentle mechanical dissociation and purified with discontinuous (10 pancreases) or continuous (8 pancreases) gradients of HCA-Ficoll in COBE 2991 cell processor. Samples were collected in duplicate for determination of the quantity of islets, islet equivalents (IEQ), and the purity. The weights of the pancreases before and after connective tissue removal and pancreas duct perfusion, and the quantity of islets obtained (including islets quantity of different diameters and total IEQ) after dissociation were not significantly different. Continuous gradient of HCA-Ficoll, compared with discontinuous gradient, resulted in significantly greater final islet quantity (55,000 IEQ vs 206,000 IEQ, P=0.000) and islet purity (58.0%-/+8.0% vs 33.5%-/+10.3%, P=0.000) and also greater number of islets with a diameter lager than 200 microm (P<0.01). Continuous density gradient centrifugation can be more effective than discontinuous gradient in islet purification.


Experimental chlamydiosis in wild and domestic lagomorphs.
Chlamydia psittaci (strain M56, the agent of epizootic chlamydiosis of muskrats and hares) was highly lethal for the snowshoe hare (Lepus americans) following intravenous inoculation, whereas the agent was much less virulent for cottontail (Sylvilagus floridanus) and albino domestic rabbits (Oryctolagus cuniculus). Tissue titres of strain M56 were generally higher after 96 hr in the snowshoe hare than in tissues of the other lagomorphs. Spleen, liver and bone marrow were apparently the chief sites of primary multiplication of strain M56 in the hare. Virulence appeared to be very host specific in that only strain M56 among the six chlamydiae tested was highly lethal for the snowshoe hare.


Yoga, as a transitional platform to more active lifestyle: a 6-month pilot study in the USA.
A 6-month pilot study explored the effects of a yoga program on the physical activity (PA) level of overweight or obese sedentary adults. Fourteen community-dwelling overweight or obese sedentary adults participated in a 6-month program (2-month yoga program and 4-month follow-up) delivered by two types of instruction [the direct guidance of an instructor (face-to-face group) vs. the self-learning method of using a DVD (DVD group)]. Measurements included program adherence (class attendance and home practice; min/week) and level of PA [metabolic equivalent (MET)-hour/week] at baseline, 2, 4 and 6 months. Descriptive statistics and nonparametric tests were used to describe the sample and examine differences by group and time. There were no significant differences in demographic variables by group assigned. Participants showed significant PA changes from baseline to each measurement point. The direct guidance of an instructor was preferred over the self-learning method. At each time interval, the DVD group showed higher levels of PA than the face-to-face group; the only difference that achieved statistical significance occurred at 4 months. The PA level significantly changed over 6 months in the DVD group, but not in the face-to-face group. The results indicate that a yoga program may be utilized as a 'stepping-stone' toward regular exercise among overweight sedentary adults. Research with a larger sample is needed to further evaluate the effects of the program on the level of PA among this population.


Association of periodontal disease to anxiety and depression symptoms, and psychosocial stress factors.
A cross-sectional study was conducted to investigate if anxiety, depression and hopelessness symptoms are associated with periodontal disease. A total of 160 subjects took part in this study. Probing depth and clinical attachment level were recorded at six sites per tooth and the gingival and plaque indices were also recorded. The instruments used to assess the psychological variables (anxiety, depression, stress, psychiatric symptoms and hopelessness) were: the State-Trait Anxiety Inventory, the Beck Depression Inventory, the Life Events Scale modified by Savoia, the Self-Report Screening Questionnaire-20 and the Beck Hopelessness Scale. There was no difference in scale score means between patients with and without established periodontitis. Results of the Ordinal Logistic Regression Analysis model that included age, plaque index, smoking and psychological factors showed that patients with psychiatric symptoms (odds ratio (OR) 1.24, 95% confidence interval (CI) 0.33-4.78), depression symptoms (OR 0.57, 95% CI 0.15-2.21) and with hopelessness (OR 0.70, 95% CI 0.13-3.84) were not at a greater risk of developing established periodontitis. In this sample, no evidence was found for an association between depression, hopelessness, psychiatric symptoms and established periodontitis. The association of periodontal disease to depression, anxiety and stress should be investigated in psychiatric populations, especially in those with depression and anxiety disorders.


Direct observation of the quantum critical point in heavy fermion CeRhSi3.
We report on muon spin rotation studies of the noncentrosymmetric heavy fermion antiferromagnet CeRhSi3. A drastic and monotonic suppression of the internal fields, at the lowest measured temperature, was observed upon an increase of external pressure. Our data suggest that the ordered moments are gradually quenched with increasing pressure, in a manner different from the pressure dependence of the Néel temperature. At 23.6 kbar, the ordered magnetic moments are fully suppressed via a second-order phase transition, and T(N) is zero. Thus, we directly observed the quantum critical point at 23.6 kbar hidden inside the superconducting phase of CeRhSi3.


Surgical indications for toxic multinodular goitre.
The aim of this study was to clarify the surgical indications and the effectiveness of total thyroidectomy in the treatment of toxic multinodular goitre. From January 1998 to May 2004, 70 patients underwent total thyroidectomy in our department because of toxic multinodular goitre. In 46 patients (65.7%) the indications for total thyroidectomy were: 25 compressive goitres, 12 cervico-mediastinal goitres, 2 cases of Pemberton's sign, 5 follicular nodules with cytological atypia, and 2 cases of suspected papillary carcinoma. In 24 patients (34.3%) with failure or intolerance of previous treatment, surgical indications were: 9 persistent and 5 recurrent hyperthyroidism after medical treatment; 6 patients with cardiotoxicity; 3 patients with recurrent disease after percutaneous ethanol injection; 1 patient with antithyroid drug intolerance. The mean postoperative hospital stay was 3.2 days (range: 2-9). Transient hypocalcaemia occurred in 6 patients (8.6%) and transient unilateral recurrent laryngeal nerve injury in another 3 patients (4.2%). None of the patients had permanent hypocalcaemia or permanent recurrent laryngeal nerve injury. All 70 treated patients relieved their symptoms and became biochemically hypothyroid after the operation. Total thyroidectomy results in a rapid, reliable resolution of hyperthyroidism and removal of multinodular goitre, requires no re-treatment, removes any coexisting malignancy, and post-surgical hypothyroidism is simple to treat.


Regeneration of the adult thymus is preceded by the expansion of K5+K8+ epithelial cell progenitors and by increased expression of Trp63, cMyc and Tcf3 transcription factors in the thymic stroma.
Studies of HIV-1-infected individuals on anti-retroviral therapies and of patients receiving lymphoablating treatments indicate that the thymus retains restorative capacity even in adults. The contributions of the thymic epithelial cells (TECs) to the regeneration of the thymus and the identity of epithelial cell progenitors were evaluated in murine models of transient thymic atrophy followed by a complete regeneration. Using microarray approach, we analyzed the pattern of gene expression in TECs sorted from mice that were depleted of thymocytes by steroid treatment or by irradiation. The initial analysis identified significant increases in the mRNA for cMyc, Trp63 and Tcf3 transcription factors known to be expressed in early epithelial cell progenitors in tissues other than the thymus. Immunohistochemistry showed that in involuted thymuses, the cMyc and Trp63 proteins were expressed in a subset of cortical thymic epithelial cells (cTECs) that were keratin 5 positive (K5(+)), typifying cTEC precursors. Importantly, confocal microscopy established that epithelial cells with the phenotype of putative TEC progenitors (i.e. K5(+)K8(+)) expressed the Trp63 protein and confirmed that K5(+)K8(+) TEC progenitors expanded significantly during atrophy and prior to the thymic regeneration. Thus, our data demonstrated for the first time that critical steps in the recovery of the adult thymus include expansion of TEC progenitors and elevated expression of Trp63, cMyc and Tcf3 transcription factors in the thymic stroma. These results suggest that TEC progenitors could be reactivated in the adult thymus and, therefore, reactivation of TEC progenitors could provide a new approach for thymic reconstitution.


Gut-brain pathogenesis of post-acute COVID-19 neurocognitive symptoms.
Approximately one third of non-hospitalized coronavirus disease of 2019 (COVID-19) patients report chronic symptoms after recovering from the acute stage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Some of the most persistent and common complaints of this post-acute COVID-19 syndrome (PACS) are cognitive in nature, described subjectively as "brain fog" and also objectively measured as deficits in executive function, working memory, attention, and processing speed. The mechanisms of these chronic cognitive sequelae are currently not understood. SARS-CoV-2 inflicts damage to cerebral blood vessels and the intestinal wall by binding to angiotensin-converting enzyme 2 (ACE2) receptors and also by evoking production of high levels of systemic cytokines, compromising the brain's neurovascular unit, degrading the intestinal barrier, and potentially increasing the permeability of both to harmful substances. Such substances are hypothesized to be produced in the gut by pathogenic microbiota that, given the profound effects COVID-19 has on the gastrointestinal system, may fourish as a result of intestinal post-COVID-19 dysbiosis. COVID-19 may therefore create a scenario in which neurotoxic and neuroinflammatory substances readily proliferate from the gut lumen and encounter a weakened neurovascular unit, gaining access to the brain and subsequently producing cognitive deficits. Here, we review this proposed PACS pathogenesis along the gut-brain axis, while also identifying specific methodologies that are currently available to experimentally measure each individual component of the model.


Prevention and management of adverse effects of disease modifying treatments in multiple sclerosis.
To summarize the currently known side effects of the approved therapies of multiple sclerosis and to suggest monitoring procedures. The progress in the treatment of multiple sclerosis with new very effective therapies is accompanied by a number of side effects. Some of these have already been described in the approval studies, but some only after approval in a real world situation. The reason for this is the short duration of the clinical studies, the very heterogeneous patient profile in the real world setting with a number of comorbidities, pretherapies, and wider age range. The side effects may occur during application of therapies or afterwards during the course of the treatment. The side effects may range from mild infections, mild laboratory abnormalities, secondary autoimmune diseases to life-threatening side effects such as progressive multifocal leukoencephalopathy. It has to be pointed out that these side effects are not to be considered as final and neurologists should be vigilant against new unknown side effects. The doctor should be aware of these undesirable effects, should weigh the benefits of the therapies against the risks, but at the same time she/he should keep in mind that multiple sclerosis can be a very disabling disease if not treated properly.


Post-Transcriptional Regulation of Anti-Apoptotic BCL2 Family Members.
Anti-apoptotic B cell lymphoma 2 (BCL2) family members (BCL2, MCL1, BCLxL, BCLW, and BFL1) are key players in the regulation of intrinsic apoptosis. Dysregulation of these proteins not only impairs normal development, but also contributes to tumor progression and resistance to various anti-cancer therapies. Therefore, cells maintain strict control over the expression of anti-apoptotic BCL2 family members using multiple mechanisms. Over the past two decades, the importance of post-transcriptional regulation of mRNA in controlling gene expression and its impact on normal homeostasis and disease have begun to be appreciated. In this review, we discuss the RNA binding proteins (RBPs) and microRNAs (miRNAs) that mediate post-transcriptional regulation of the anti-apoptotic BCL2 family members. We describe their roles and impact on alternative splicing, mRNA turnover, and mRNA subcellular localization. We also point out the importance of future studies in characterizing the crosstalk between RBPs and miRNAs in regulating anti-apoptotic BCL2 family member expression and ultimately apoptosis.


Sex determines effect of physical activity on diet preference: Association of striatal opioids and gut microbiota composition.
Previous studies suggest an interaction between the level of physical activity and diet preference. However, this relationship has not been well characterized for sex differences that may exist. The present study examined the influence of sex on diet preference in male and female Wistar rats that were housed under either sedentary (no wheel access) (SED) or voluntary wheel running access (RUN) conditions. Following a 1 week acclimation period to these conditions, standard chow was replaced with concurrent ad libitum access to a choice of 3 pelleted diets (high-fat, high-sucrose, and high-corn starch) in the home cage. SED and RUN conditions remained throughout the next 4 week diet preference assessment period. Body weight, running distance, and intake of each diet were measured daily. At the conclusion of the 4 week diet preference test, animals were sacrificed and brains were collected for mRNA analysis. Fecal samples were also collected before and after the 4 week diet preference phase to characterize microbiota composition. Results indicate sex dependent interactions between physical activity and both behavioral and physiological measures. Females in both RUN and SED conditions preferred the high-fat diet, consuming significantly more high-fat diet than either of the other two diets. While male SED rats also preferred the high-fat diet, male RUN rats consumed significantly less high-fat diet than the other groups, instead preferring all three diets equally. There was also a sex dependent influence of physical activity on both reward related opioid mRNA expression in the ventral striatum and the characterization of gut microbiota. The significant sex differences in response to physical activity observed through both behavioral and physiological measures suggest potential motivational or metabolic difference between males and females. The findings highlight the necessity for further exploration between male and female response to physical activity and feeding behavior.


Sarcoma following irradiation for breast cancer. Report of three unusual cases including one malignant mesenchymoma of bone.
Three cases of sarcoma developing after irradiation for breast cancer are reported. A malignant mesenchymoma in the sternum--a combination of osteogenic sarcoma and rhabdomyosarcoma--is the first documented case of its kind occurring after radiation therapy. Of the other two tumors one was an extraskeletal osteogenic sarcoma in the soft tissues of the thoracic wall and one a rhabdomyosarcoma in the axilla.


Pathophysiology of in-vitro induced filaments, spheroplasts and rod-shaped bacteria in neutropenic mice.
This study compared the in-vitro properties and in-vivo effects of Escherichia coli filaments, spheroplasts and normal cells in a murine thigh infection model. E. coli was exposed to ceftazidime, meropenem or saline to obtain filaments, spheroplasts or normal bacilli, which were then injected into neutropenic mice. After 24 h, morphology, CFUs, local and circulating endotoxin levels, cytokine levels and mortality were recorded, and correlations between bacterial and host parameters of infection were investigated. Filaments and spheroplasts contained more endotoxin/CFU than controls. Histological studies showed that morphologically altered bacteria changed into rod-shaped cells in the absence of antibiotics. Bacterial spread to the liver was significantly higher in mice challenged with rod-shaped cells, compared with antibiotic-exposed bacteria (p 0.007). Muscle endotoxin levels correlated significantly with circulating interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha, and both pro-inflammatory cytokines were correlated significantly (p 0.011). Despite a tendency toward higher local and systemic concentrations of endotoxin in the filament group, inflammatory responses and survival did not differ between groups. It was concluded that morphologically altered bacteria contain more endotoxin and can regain a rod shape after withdrawal of antibiotics, while non-antibiotic-exposed bacteria show greater spread to the liver. There was a clear intra-individual relationship between local endotoxin, systemic endotoxin, TNF-alpha and IL-6 production, but these parameters did not differ among groups.