The head and the foot inhibitor from hydra are not dowex artefacts.
In a recent publication in this journal (Berking 1983) it was claimed (1) that the head inhibitor we isolated from hydra is a Dowex artefact, (2) that a separate foot inhibitor does not exist in hydra and (3) that the only inhibitor that has so far been isolated from hydra is one which inhibits head and foot regeneration equally well. These statements are incorrect and require a response. In the following, I would like to summarise our evidence that the inhibitors isolated from hydra, including Berking's inhibitor, have different specificities for head and foot regeneration. In addition, I would like to show that none of our substances are Dowex artefacts.


Neuropsychological and neuroendocrinological disturbances associated with extracerebral cysts of the anterior and middle cranial fossa.
In ten adult patients various clinical signs and symptoms led to the diagnosis of an arachnoid cyst in the anterior and middle cranial fossa. In this study a functional relationship between these cysts and disturbances of higher cognitive processes is described. In addition, neuroendocrinological impairment were caused by arachnoid cysts reaching into the suprasellar cistern. Considering the short medical history of our patients we presumed the disturbances not to be primary, but rather secondary, caused by an expansion of the cysts' volume.


Evaluation of diabetes-related short-chain organic acids in rat plasma by capillary electrophoresis.
A capillary zone electrophoresis method was optimised to analyse low-molecular-mass organic acids for the purpose of monitoring diabetes in rat plasma. The method included acetoacetic, 2-hydroxybutyric, lactic and uric acids. A variation in the background electrolyte allowed us to measure pyruvic acid in the same sample. Conditions have been optimised for measuring a large number of plasma samples corresponding to control and diabetic rats. Samples were mixed with acetonitrile (1:1, v/v) to precipitate proteins, centrifuged, diluted and injected. Tropic acid was chosen as an adequate internal standard. Separation was developed with reversed voltage by using a column cartridge pre-treated with polyacrylamide. Two electrophoretic buffers were employed: 0.150 M H3PO4 made up pH 6.20 with NaOH and 0.3 mM CaCl2 for acetoacetic, hydroxybutyric, lactic and uric acids, and 200 mM phosphate-10 mM acetate pH 4.0 for pyruvic acid, both with direct detection at 200 nm. The method was validated for linearity, accuracy and precision and the limits of quantification were calculated. The method was successfully applied to analyse these organic acids in control and diabetic animals. Acetoacetic and hydroxybutyric acids were clearly increased in diabetic rats, meanwhile no statistically significant difference has been found with the other acids.


Reticular Pseudodrusen in Late-Onset Retinal Degeneration.
To characterize the association of reticular pseudodrusen (RPD) with late-onset retinal degeneration (L-ORD) using multimodal imaging. Prospective, 2-center, longitudinal case series. Twenty-nine patients with L-ORD. All patients were evaluated within a 3-year interval with near-infrared reflectance, fundus autofluorescence, and spectral-domain OCT. In addition, a subset of patients also underwent indocyanine green angiography, fundus fluorescein angiography, mesopic microperimetry, and multifocal electroretinography. Prevalence, topographic distribution, and temporal phenotypic changes of RPD in L-ORD. A total of 29 patients with molecularly confirmed L-ORD were included in this prospective study. Reticular pseudodrusen was detected in 18 patients (62%) at baseline, 10 of whom were men. The prevalence of RPD varied with age. The mean age of RPD patients was 57.3 ± 7.2 years. Reticular pseudodrusen was not seen in patients younger than the fifth decade of life (n = 3 patients) or in the eighth decade of life (n = 5 patients). Reticular pseudodrusen were found commonly in the macula with relative sparing of the fovea and also were identified in the peripheral retina. The morphologic features of RPD changed with follow-up. Two patients (3 eyes) demonstrated RPD regression. Reticular pseudodrusen is found frequently in patients with L-ORD and at a younger age than in individuals with age-related macular degeneration (AMD). Reticular pseudodrusen exhibits quick formation and collapse, change in type and morphologic features with time, and relative foveal sparing and also has a peripheral retinal location in L-ORD.


The cost-effectiveness of gene therapy for severe hemophilia B: a microsimulation study from the United States perspective.
Adeno-associated virus (AAV)-mediated gene therapy is a novel treatment promising to reduce morbidity associated with hemophilia. Although multiple clinical trials continue to evaluate efficacy and safety, limited cost-effectiveness data have been published. This study compared the potential cost-effectiveness of AAV-mediated factor IX (FIX)-Padua gene therapy for patients with severe hemophilia B in the United States vs on-demand FIX replacement and primary FIX prophylaxis, using either standard or extended half-life FIX products. A microsimulation Markov model was constructed, and transition probabilities between health states and utilities were informed by using published data. Costs were aggregated by using a microcosting approach. A time horizon from 18 years old until death, from the perspective of a third-party payer in the United States, was conducted. Gene therapy was more cost-effective than both alternatives considering a $150 000/quality-adjusted life-year threshold. The price for gene therapy was assumed to be $2 000 000 in the base case scenario; however, one of the 1-way sensitivity analyses was conducted by using observed manufacturing, administration, and 5-year follow-up costs of $87 198 for AAV-mediated gene therapy vector as derived from the manufacturing facility and clinical practice at St Jude Children's Research Hospital. One-way sensitivity analyses revealed 10 of 102 scenarios in which gene therapy was not cost-effective compared with alternative treatments. Notably, gene therapy remained cost-effective in a hypothetical scenario in which we estimated that the discounted factor concentrate price was 20% of the wholesale acquisition cost in the United States. Probabilistic sensitivity analysis estimated gene therapy to be cost-effective at 92% of simulations considering a $150 000/quality-adjusted life-year threshold. In conclusion, based on detailed simulation inputs and assumptions, gene therapy was more cost-effective than on-demand treatment and prophylaxis for patients with severe hemophilia B.


Sargachromenol Isolated from Sargassum horneri Inhibits Particulate Matter-Induced Inflammation in Macrophages through Toll-like Receptor-Mediated Cell Signaling Pathways.
Sargassum horneri is an invasive brown seaweed that grows along the shallow coastal areas of the Korean peninsula, which are potentially harmful to fisheries and natural habitats in the areas where it is accumulated. Therefore, the author attempted to evaluate the anti-inflammatory mechanism of Sargachromenol isolated from S. horneri against particulate matter (PM)-stimulated RAW 264.7 macrophages. PM is a potent inducer of respiratory diseases such as lung dysfunctions and cancers. In the present study, the anti-inflammatory properties of Sargachromenol were validated using enzyme-linked immunosorbent assay (ELISA), Western blots, and RT-qPCR experiments. According to the results, Sargachromenol significantly downregulated the PM-induced proinflammatory cytokines, Prostaglandin E2 (PGE2), and Nitric Oxide (NO) secretion via blocking downstream activation of Toll-like receptor (TLR)-mediated nuclear factor kappa B (NF-κB) and MAPKs phosphorylation. Thus, Sargachromenol is a potential candidate for innovation in various fields including pharmaceuticals, cosmeceuticals, and functional food.


Eschar and neck lymphadenopathy caused by Francisella tularensis after a tick bite: a case report.
In 25 to 35% of cases, the aetiological agent of scalp eschar and neck lymphadenopathy after a tick bite remains undetermined. To date, Rickettsia slovaca, Rickettsia raoultii and more recently Bartonella henselae have been associated with this syndrome. A four-year-old Caucasian boy was admitted to hospital with fever, vomiting and abdominal pain. On physical examination, an inflammatory and suppurating eschar was seen on the scalp, with multiple enlarged cervical lymph nodes on both sides. Although no tick was found in this scalp lesion, a diagnosis of tick-borne lymphadenopathy was suggested, and explored by serology testing and polymerase chain reaction of a biopsy from the eschar. Francisella tularensis DNA was found in the skin biopsy and the serology showed titres consistent with tularaemia. This is, to the best of our knowledge, the first reported case of scalp eschar and neck lymphadenopathy after tick bite infection caused by F. tularensis.


Analyzing expression and phosphorylation of the EGF receptor in HNSCC.
Overexpression of the epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinomas (HNSCC) is considered to cause increased EGFR activity, which adds to tumorigenicity and therapy resistance. Since it is still unclear, whether EGFR expression is indeed associated with increased activity in HNSCC, we analyzed the relationship between EGFR expression and auto-phosphorylation as a surrogate marker for activity. We used a tissue micro array, fresh frozen HNSCC tumor and corresponding normal tissue samples and a large panel of HNSCC cell lines. While we observed substantial overexpression only in approximately 20% of HNSCC, we also observed strong discrepancies between EGFR protein expression and auto-phosphorylation in HNSCC cell lines as well as in tumor specimens using Western blot and SH2-profiling; for the majority of HNSCC EGFR expression therefore seems not to be correlated with EGFR auto-phosphorylation. Blocking of EGFR activity by cetuximab and erlotinib points to increased EGFR activity in samples with increased basal auto-phosphorylation. However, we could also identify cells with low basal phosphorylation but relevant EGFR activity. In summary, our data demonstrate that EGFR expression and activity are not well correlated. Therefore EGFR positivity is no reliable surrogate marker for EGFR activity, arguing the need for alternative biomarkers or functional predictive tests.


Epidemiology of invasive meningococcal disease in Germany, 2002-2010, and impact of vaccination with meningococcal C conjugate vaccine.
To analyse serogroup (Sg)- and finetype-specific invasive meningococcal disease burden (IMD) in Germany, 2002-2010, with emphasis on effects of vaccination with conjugate SgC vaccines targeting one-year old children since 2006, including individual-based catch-up to 17 years of age. Serogroup- and age-specific IMD incidence and trends were calculated using statutory surveillance data. The national reference laboratory performed genetic finetyping. Vaccination uptake data were obtained from school entry surveys and prescription monitoring. In persons <25 years, SgB and SgC IMD incidence decreased significantly from 0.63 to 0.32/100,000 and 0.26 to 0.10/100,000, respectively. The decline was significantly steeper for SgC than SgB in 1-5 year-olds, the primary vaccination target group, but not other ages. The slope of the SgC incidence curves was similar before and after vaccination implementation in all age groups; however, the decrease in incidence was steeper in states with higher vaccination uptake. Declining SgC incidence was associated with decreased SgC finetype diversity. An increase in SgY incidence was limited to adults. Results suggest effects of the German SgC vaccination strategy are limited, although interpretation is complicated by already low and decreasing incidence before vaccination. More effective use of vaccination resources might be achieved by rigorously targeting adolescents in addition to 1-year-olds.


Aedes albopictus diversity and relationships in south-western Europe and Brazil by rDNA/mtDNA and phenotypic analyses: ITS-2, a useful marker for spread studies.
Aedes albopictus is a very invasive mosquito, which has recently colonized tropical and temperate regions worldwide. Of concern is its role in the spread of emerging or re-emerging mosquito-borne diseases. Ae. albopictus from south-western Europe and Brazil were studied to infer genetic and phenetic diversity at intra-individual, intra-population and inter-population levels, and to analyse its spread. Genotyping was made by rDNA 5.8S-ITS-2 and mtDNA cox1 sequencing to assess haplotype and nucleotide diversity, genetic distances and phylogenetic networks. Male and female phenotyping included combined landmark-and outlined-based geometric morphometrics of wing size and shape. Specimens from seven populations from Spain, France and Brazil provided 12 cox1 and 162 5.8S-ITS-2 haplotypes, with great genetic variability difference between both markers (0.9% vs 31.2%). Five cox1 haplotypes were shared with other countries, mainly Italy, USA and China, but none was shared between Europe and Brazil. The 5.8S-ITS-2 showed 2-7 intra-individual (mean 4.7) and 16-34 intra-/inter-population haplotypes (24.7), including haplotypes shared between Spain, France and Brazil. A 4.3% of ITS-2 haplotypes were shared, mainly with Italy, USA and Thailand, evidencing worldwide spread and introductions from areas where recent outbreaks of Ae. albopictus-transmitted pathogens occurred. Wing size showed sex differences. Wing shape distinguished between Brazilian and European specimens. Both genetic and morphometric markers showed differences between insular Spain and continental Spain, France and Brazil. ITS-2 proves to be a useful marker to assess Ae. albopictus spread, providing pronouncedly more information than cox1, including intra-individual, intra-population and inter-population levels, furnishing a complete overview of the evolutionary exchanges followed by this mosquito. Wing morphometry proves to be a useful phenotyping marker, allowing to distinguish different populations at the level of both male and female specimens. Results indicate the need for periodic surveillance monitorings to verify that no Ae. albopictus with high virus transmission capacity is introduced into Europe.


Physical mechanisms behind the wet adhesion: From amphibian toe-pad to biomimetics.
Some amphibians, such as tree frogs, torrent frogs, newts, are able to climb or attach to wet slippery smooth surfaces, even in a vertical or overhanging state, by their reliable reversible adhesions developed on the epidermal of toe pads. It is widely believed that such outstanding function originates from the possible factors of the specialized evolutions of surficial micro/nanostructures, the chemical components of secreted mucus, the solid-liquid behavior of epidermal and the bulk softness of toe pads. In this review, we summarize the main physical mechanisms of these factors behaving underlying the wet adhesion of toe pads from the researches on biological models to artificial counterparts. The discussion of the organism attachments, the interfacial physical forces and the switchable strategies for artificial wet adhesion are also included. The paper gives a deeply, comprehensively understanding of the characters of wet adhesives on amphibians, which performs necessarily for the new strategies of exploring artificial adhesive surfaces.


The translation initiation site of recombinant Trypanosoma brucei ornithine decarboxylase varies with different promoters.
Expression of the Trypanosoma brucei ornithine decarboxylase (ODC) gene in Escherichia coli behind the lambda phage PR promoter led to the production of a recombinant enzyme having the same subunit molecular weight as the native enzyme [4]. However, when the same gene is expressed behind the tac promoter or the phoA promoter, the ODCs produced by the transformed E. coli have subunit molecular weights approximately 2 kDa higher than that of the native enzyme. Amino terminal sequencing of the recombinant proteins indicates that the ODC synthesized under control of the lambda PR promoter actually starts at the second methionine (Met23) of the open reading frame, whereas those produced in the latter two cases begin at the first methionine (Met1). Analysis of the 5'-end of T. brucei ODC mRNA supports the conclusion that translation initiates at Met23. We postulate that, for the lambda PR promoter, translation initiates at Met23 instead of Met1 because of the formation of a stable secondary structure in the region of the Met1 and the presence of a good E. coli consensus translation initiation site upstream of Met23. We have constructed a new plasmid using the pho A promoter to express recombinant T. brucei ODC starting at Met23 in large quantities.


One Hundred Twenty-four Laparoscopic-Assisted Vaginal Hysterectomies
Laparoscopic-assisted vaginal hysterectomy (LAVH) is not yet widely practiced in Taiwan, but interest in this operation is increasing as our knowledge of operative laparoscopy expands. From October 1994 to December 1995, 124 LAVHs were performed. The endoscopic stapler divides tissues and achieves hemostasis quite easily, but its cost is a disadvantage. Kleppinger bipolar forceps for hemostasis and scissors for division are less expensive for the average hospital. Ureteral injury is a crucial issue in LAVH, and is linked to various stages of the operation. Identifying the ureter before the operation and dissecting it after division of the infundibulopelvic ligament are essential to avoid ureteral injury.


RNAi for Western Corn Rootworm Management: Lessons Learned, Challenges, and Future Directions.
The western corn rootworm (WCR), Diabrotica virgifera virgifera LeConte, is considered one of the most economically important pests of maize (Zea mays L.) in the United States (U.S.) Corn Belt with costs of management and yield losses exceeding USD ~1-2 billion annually. WCR management has proven challenging given the ability of this insect to evolve resistance to multiple management strategies including synthetic insecticides, cultural practices, and plant-incorporated protectants, generating a constant need to develop new management tools. One of the most recent developments is maize expressing double-stranded hairpin RNA structures targeting housekeeping genes, which triggers an RNA interference (RNAi) response and eventually leads to insect death. Following the first description of in planta RNAi in 2007, traits targeting multiple genes have been explored. In June 2017, the U.S. Environmental Protection Agency approved the first in planta RNAi product against insects for commercial use. This product expresses a dsRNA targeting the WCR snf7 gene in combination with Bt proteins (Cry3Bb1 and Cry34Ab1/Cry35Ab1) to improve trait durability and will be introduced for commercial use in 2022.


Mitochondrial dysfunction in peripheral blood mononuclear cells in pediatric septic shock.
Mitochondrial dysfunction in peripheral blood mononuclear cells has been linked to immune dysregulation and organ failure in adult sepsis, but pediatric data are limited. We hypothesized that pediatric septic shock patients exhibit mitochondrial dysfunction within peripheral blood mononuclear cells which in turn correlates with global organ injury. Prospective observational study. Academic PICU. Thirteen pediatric patients with septic shock and greater than or equal to two organ failures and 11 PICU controls without sepsis or organ failure. Ex vivo measurements of mitochondrial oxygen consumption and membrane potential (ΔΨm) were performed in intact peripheral blood mononuclear cells on day 1-2 and day 5-7 of septic illness and in controls. The Pediatric Logistic Organ Dysfunction score, inotrope score, and organ failure-free days were determined from medical records. Spare respiratory capacity, an index of bioenergetic reserve, was lower in septic peripheral blood mononuclear cells on day 1-2 (median, 1.81; interquartile range, 0.52-2.09 pmol O2/s/10 cells) compared with controls (5.55; 2.80-7.21; p = 0.03). Spare respiratory capacity normalized by day 5-7. Patients with sepsis on day 1-2 exhibited a higher ratio of LEAK to maximal respiration than controls (17% vs < 1%; p = 0.047) with normalization by day 5-7 (1%; p = 0.008), suggesting mitochondrial uncoupling early in sepsis. However, septic peripheral blood mononuclear cells exhibited no differences in basal or adenosine triphosphate-linked oxygen consumption or ΔΨm. Oxygen consumption did not correlate with Pediatric Logistic Organ Dysfunction score, inotrope score, or organ failure-free days (all p > 0.05). Although there was a weak overall association between ΔΨm on day 1-2 and organ failure-free days (Spearman ρ = 0.56, p = 0.06), patients with sepsis with normal organ function by day 7 exhibited higher ΔΨm on day 1-2 compared with patients with organ failure for more than 7 days (p = 0.04). Mitochondrial dysfunction was present in peripheral blood mononuclear cells in pediatric sepsis, evidenced by decreased bioenergetic reserve and increased uncoupling. Mitochondrial membrane potential, but not respiration, was associated with duration of organ injury.


Granule cell dispersion is associated with hippocampal neuronal cell loss, initial precipitating injury, and other clinical features in mesial temporal lobe epilepsy and hippocampal sclerosis.
To characterize a 10-year series of patients with mesial temporal lobe epilepsy (MTLE) and unilateral hippocampal sclerosis (HS) and determine the histopathological characteristic of the association between granule cell dispersion (GCD) and hippocampal neuronal loss. The study included 108 MTLE/HS patients. Histopathological analyses were performed in NeuN-stained hippocampal sections for HS pattern, neuronal density, dentate gyrus (DG) pathology, and granule cell layer width. Statistical tests investigated the association between DG pathologies and HS patterns, as well as the correlation of DG width with total hippocampal and subfield-specific neuronal densities. Fifty-six patients (51.9%) presented right HS. All the four ILAE HS patterns were represented (90 Type 1, 11 Type 2, 2 Type 3, and 5 no-HS). Sixty-seven patients (62.0%) presented GCD, 39 (36.1%) normal DG, and 2 (1.9%) narrow DG. GCD was associated with initial precipitating injury, higher numbers of monthly focal seizures and lifetime bilateral tonic-clonic seizures, longer epilepsy duration, and older age at surgery. GCD was prevalent in all HS patterns, except for Type 2 (81.8% normal versus 18.2% GCD, p = 0.005). GCD was associated with total hippocampal and subfield-specific neuronal loss, except for CA1. DG width correlated with total hippocampal (r = -0.201, p = 0.037) and CA4 neuronal densities (r = -0.299, p = 0.002). Patients with HS Type 1 had better surgical outcomes, with 51 (61.4%) seizure-free in the first year post-surgery. This study confirmed that seizure control in MTLE/HS patients submitted to surgical treatment is comparable worldwide. Moreover, histopathological analyses showed an association between GCD and hippocampal neuronal loss, especially in the CA4 subfield.


Casein kinase II from Caenorhabditis elegans. Properties and developmental regulation of the enzyme; cloning and sequence analyses of cDNA and the gene for the catalytic subunit.
The nematode Caenorhabditis elegans provides a model system for investigating the structure, function, and regulation of casein kinase II. Cytosols from C. elegans embryos and gravid adults, which contain fertilized eggs and embryos, are enriched in casein kinase II activity; cytosols from newly hatched larva, four subsequent larval stages, and immature adults exhibit casein kinase II levels that are 3-10-fold lower than those observed in embryo cytosol. C. elegans casein kinase II contains alpha (Mr = 42,000) and beta (Mr = 29,000) subunits and has a Stokes radius of 50 nm. The enzyme utilizes ATP and GTP as substrates, is potently inhibited by heparin and undergoes autophosphorylation. Sequence analyses of cloned cDNAs corresponding to the 1.7-kilobase mRNA encoding the alpha (catalytic) subunit of casein kinase II indicate that the alpha polypeptide contains 359 amino acid residues. Variations in the abundance of casein kinase II alpha mRNA are coordinated with changes in enzyme activity during C. elegans development, indicating that alpha subunit expression is controlled at a pretranslational level. However, the magnitude of the developmentally controlled changes in phosphotransferase activity exceeded the corresponding increments in alpha subunit mRNA content. This suggests that translational and/or post-translational mechanisms also play an important role in the developmental regulation of C. elegans casein kinase II activity. The 2.9-kilobase casein kinase II alpha gene is divided into eight exons by intervening sequences ranging from 48 to 457 base pairs in length. The alpha gene promoter contains a TATA box, and a unique transcription start site has been identified. The intron/exon organization of the casein kinase II alpha gene differs markedly from the gene structure of the catalytic subunit of murine cAMP-dependent protein kinase (Chrivia, J. C., Uhler, M. D., and McKnight, G. S. (1988) J. Biol. Chem. 263, 5739-5744).


The synergistic interaction between urbanicity and maternal education affecting childcare pressure related to autism spectrum disorder in two national birth cohort studies.
To gain a holistic approach for parental help-seeking behavior and ASD diagnosis, this study aimed to use two national birth cohort study datasets to investigate the pathway relationship between personal and social/environmental factors, including maternal perceived childcare pressure, maternal level of education, urbanization at age 3, and the chance of receiving a autism spectrum disorder (ASD) diagnosis at when children are aged 5.5 years (2.5 years later). The 2003 Taiwan Birth Cohort Pilot Study (TBCS-p; N = 1618) and 2005 Taiwan Birth Cohort Study (TBCS; N = 19,183) datasets were used. The TBCS-p and TBCS both showed similar prevalence of ASD (0.3-0.4%). Children with ASD characteristics, as measured using the Modified Checklist of Autism in Toddlers, had 8.27-18.20 times increased likelihood of receiving ASD diagnosis [TBCS confidence interval (CF) of 5.32-12.86; TBCS-p CF of 2.03-163.46]. Pathway analysis showed that, although having a mother with higher education or who lived in a city decreased the chance for ASD diagnosis, the interactive effect of a maternal higher level of education and living in a city led to an increased likelihood for ASD diagnosis. Additionally, mothers who perceived a higher level of childcare pressure were also more likely to seek medical assistance and diagnosis. Access to healthcare (living in the city), maternal level of awareness (level of education), and perceived childcare pressure are all factors that influence help-seeking behavior and diagnosis. Therefore, medical professionals should pay special attention to the developmental condition of children in underserved backgrounds and rural areas to prevent delayed diagnosis.


[Opioid use in osteoarthritis: From guidelines to clinical care].
Three treatment guidelines for the treatment of knee and hip osteoarthritis (OA) which pick up the aspects of treatment supported by evidence have been published. Opioid drugs have an important role in symptomatic treatment. The guidelines, the effectiveness, and the safety of opioid analgesics in osteoarthritis, as well as its implications in clinical practice are reviewed. Tramadol is the opioid with the biggest evidence of effectiveness and safety, besides being the most used in clinical practice. Strong opioids (transdermic brupenorphine or fentanyl, oxycodone, and morphine) can be used in severe pain that does not respond to other treatments. Opioids can be used in patients that have moderate or severe pain or in those with inadequate response or intolerance to NSAID's. The opioids also have a sedative effect that facilitates sleep and can improve functional limitations and anxiety. The side effects are frequent; they usually appear at the beginning of treatment and are rarely severe, but frequently force to stop treatment.


Dual-Augmented Transposition of Vertical Recti in Chronic Abducens Palsy.
To report the results of dual augmentation of vertical rectus muscle transposition (VRT) in the treatment of chronic sixth nerve palsy. Retrospective case series. This is a retrospective review of medical records of patients with chronic sixth nerve palsy who underwent dual augmented VRT with or without medial rectus (MR) recession from 2013 to 2016. Data collection included sex, age, laterality, and duration of postoperative follow-up. Pre- and postoperative limitation of abduction and adduction were recorded using a 6-point scale. Improvement of esotropia in prism diopter (PD), head turn in degrees, and limitation of abduction and adduction were reported and analyzed. Fourteen cases were identified. Mean patients' age at the time of surgery was 22.5 years. Postoperatively, esotropia and head turn were corrected by a mean of 31.3 PD and 18.2 degrees, respectively. Limited abduction was improved from -4.3 to -1.6, while in cases that underwent MR recession, adduction declined from 0.4 to -0.3. Postoperative induced small-amplitude hypertropia was reported in 3 cases. Dual augmented VRT was effective in controlling esotropia, head turn, and limited abduction associated with chronic sixth nerve palsy with low rate of induced vertical deviation. Combined MR recession carries a risk of induced limitation of adduction.


Biomarker release after percutaneous coronary intervention in patients without established myocardial infarction as assessed by cardiac magnetic resonance with late gadolinium enhancement.
This study aimed to evaluate the amount and pattern of cardiac biomarker release after elective percutaneous coronary intervention (PCI) in patients without evidence of a new myocardial infarction (MI) after the procedure as assessed by cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE). The release of myocardial necrosis biomarkers after PCI frequently occurs. However, the correlation between biomarker release and the diagnosis of procedure-related MI type 4a has been controversial. Patients with normal baseline cardiac biomarkers who were referred for elective PCI were prospectively included. CMR with LGE was performed in all of the patients before and after the intervention. Measurements of troponin I (TnI) and creatine kinase MB fraction (CK-MB) were systematically performed before and after the procedure. Patients with a new LGE on the post-procedure CMR were excluded. Of the 56 patients with no evidence of a procedure-related MI as assessed by CMR after the PCI, 48 (85.1%) exhibited an elevation of TnI above the 99th percentile. In 32 patients (57.1%), the peak was greater than five times this limit. Additionally, 17 patients (30.4%) had a CK-MB peak above the 99th percentile limit, but this peak was greater than five times the 99th percentile in only two patients (3.6%). The median peak release of TnI was 0.290 (0.061-1.09) ng/mL, which was 7.25-fold higher than the 99th percentile. In contrast to CK-MB, an abnormal release of TnI often occurs after an elective PCI procedure, despite the absence of a new LGE on CMR.


Hydro alcoholic green tea extract effect on high fat diet treated NMRI mice and 3T3L1 cells.
In order to counteract the obesity has epidemics, since current anti-obesity drugs effects remain limited, there is a need to provide new options. As a project aiming to assess potential anti obesity natural compounds, the effects of consumption of a minimal dose of green tea hydro alcoholic extract (GT) on adipocyte differentiation of 3T3L1 cell line were investigated. Obesity was induced in female NMRI mice (which are less used overall) by the use of a high fat diet. Mice were divided into four groups of control (C), treated control (TC), obese (O) and treated obese (TO). TC and TO groups received 8 mg/Kg/day of GT for 8 weeks, and weighted weekly, after what biochemical and histological parameters were measured. GT was used at doses of 100,150 and 200 µg/ml on 3T3L1, and staining with Oil-red-O was done for estimation of fat droplet accumulation. Body weight was found to be affected significantly by GT. Blood glucose levels did not show significant changes between groups, while triglycerides levels of the O group was significantly higher than the C group, but the TO group showed no significant difference with the C group upon GT treatment. Liver and visceral fat tissues showed more normalized tissue and less fat accumulation in the TO group. TO and TC groups showed an ameliorated morphologic state of liver tissues. GT was also able to decrease fat droplet formation in a dose-dependent manner. Adding a minimal amount of GT to the daily consumption may have preventive effects on fat accumulation in healthy subjects, while in obese cases, GT shows significant therapeutic effect.


Stereochemical Assessment of (φ,ψ) Outliers in Protein Structures Using Bond Geometry-Specific Ramachandran Steric-Maps.
Ramachandran validation of protein structures is commonly performed using developments, such as MolProbity. We suggest tailoring such analyses by position-wise, geometry-specific steric-maps, which show (φ,ψ) regions with steric-clash at every residue position. These maps are different from the classical steric-map because they are highly sensitive to bond length and angle values that are used, in our steric-maps, as observed in the residue positions in super-high-resolution peptide and protein structures. (φ,ψ) outliers observed in such structures seldom have steric-clash. Therefore, we propose that a (φ,ψ) outlier is unacceptable if it is located within the steric-clash region of a bond geometry-specific steric-map for a residue position. These steric-maps also suggest position-specific accessible (φ,ψ) space. The PARAMA web resource performs in-depth position-wise analysis of protein structures using bond geometry-specific steric-maps.


Relation between oxidation kinetics and reactant transport in an aqueous foam.
Aqueous foams are expected to constitute exquisite particularly suitable reactive medium for the oxidation of metals, since the reactant H+ can be supplied through the continuous liquid phase, while the reactant O2 can be transported through the gas bubbles. To test this hypothesis, we investigated the oxidation of a metallic copper cylinder immersed in an aqueous foam. To study the relation between the transport of these reactants and the kinetics of the chemical reaction we use a forced drainage setup which enables us to control both the advection velocity of the H+ ions through the foam and the foam liquid fraction. We find experimentally that the mass of dissolved copper presents a maximum with the drainage flow rate, and thus with the foam liquid fraction. Modeling analytically the transfer of H+ and O2 through the foams enables us to show that this non-monotonic behavior results from a competition between the advective flux of H+ ions and the unsteady diffusion of O2 through the thin liquid films which tends to be slower as the area of the thin liquid films decreases with the drainage flow rate and the liquid fraction. This study shows for the first time how to optimize the foam structure and drainage flow in reactive foams in which the reactants are present both in the liquid and gaseous phases.


Chemical Characterisation-Biological Evaluation of Greek Cultivar Cardoon Seeds (Cynara cardunculus). A By-product with Potential High Added Value.
Cynara cardunculus (artichoke) is a perennial plant of the Mediterranean basin, known since antiquity as food and for its therapeutic properties. Cynara is a relatively small genus with two cultivated species and one wild one. Recently, successful efforts have been made to cultivate wild cardoon and monetise it as a bioenergy crop. In this study, the seeds of an established Greek cultivar of C. cardunculus, cultivated in the experimental field and used as biofuel, have been researched for their chemical profile and nutritional value. According to the results, six lignans were isolated [arctigenin, arctiin, trachelogenin, tracheloside, cynarinine, and ethylate of trachelogenin (isolated for the first time from a natural source)] as well as the most characteristic metabolites of the genus (linoleic acid, trilinolein, and 3,5-dicaffeoylquinic acid). Moreover, the total phenolic content (31.18 - 54.51 mg gallic acid equivalents/g extract) and antioxidant and enzyme inhibitory activities of the seeds have been evaluated and showed strong antioxidant properties (44.42 - 516.81 mg gallic acid equivalents/g extract) as well as satisfactory bleaching (enzyme tyrosinase, 16.95 - 23.80 mg kojic acid equivalents/g extract), antidiabetic (enzymes a-amylase, a-glucosidase, 0.14 - 1.75 mmol acarbose equivalents/g extract), and protective against neurodegenerative disease (cholinesterase enzymes, 0.49 - 1.22 mg galanthamine equivalents/g extract) activities. The nutritional evaluation of the seeds confirmed them as a rich source of unsaturated fatty acids, dietary fibre (24.1%), and high protein content (19.3%). It is noteworthy that such a neglected bioactive by-product, with essentially high nutritional value, as the studied seeds could be investigated for its value-added applications towards food and food supplements areas.


Anti-mitochondrial autoantibodies are associated with cardiomyopathy, dysphagia, and features of more severe disease in adult-onset myositis.
We analyzed the prevalence of anti-mitochondrial autoantibodies (AMA) in adult- and juvenile-onset myositis longitudinal cohorts and investigated phenotypic differences in myositis patients with AMA. We screened sera from myositis patients including 619 adult- and 371 juvenile-onset dermatomyositis (DM, JDM), polymyositis (PM, JPM), inclusion body myositis (IBM), or amyopathic DM patients and from healthy controls, including 164 adults and 92 children, for AMA by ELISA. Clinical characteristics were compared between myositis patients with and without AMA. AMA were present in 5% of adult myositis patients (16 of 216 DM, 10 of 222 PM, 4 of 140 IBM, 1 of 19 amyopathic DM), 1% of juvenile myositis patients (3 of 302 JDM, 1 of 25 JPM), and 1% of both adult and juvenile healthy controls. In patients with adult-onset myositis, AMA were associated with persistent muscle weakness, Raynaud's phenomenon, dysphagia, and cardiomyopathy. Adult myositis patients with AMA may have more severe or treatment refractory disease, as they more frequently received glucocorticoids and intravenous immunoglobulin. In juvenile myositis, children with AMA often had falling episodes and dysphagia, but no other clinical features or medications were significantly associated with AMA. AMA are present in 5% of adult myositis patients and associated with cardiomyopathy, dysphagia, and other signs of severe disease. The prevalence of AMA is not increased in patients with juvenile myositis compared to age-matched healthy controls. Our data suggest that the presence of AMA in adult myositis patients should prompt screening for cardiac and swallowing involvement. Key Points • Approximately 5% of a large North American cohort of adult myositis patients have anti-mitochondrial autoantibodies. • Adults with anti-mitochondrial autoantibodies often have chronic weakness, Raynaud's, dysphagia, cardiomyopathy, and more severe disease. • Anti-mitochondrial autoantibodies are rare in juvenile myositis and not associated with a specific clinical phenotype.


[Cognitive disorders of head trauma patients].
The repercussions of cognitive disorders resulting from a traumatic brain injury are considerable in patients' daily life. Their quality of life and that of their families is significantly reduced; their reintegration into working life difficult. This chronic cognitive disability requires adapted treatment.


Mycobacterium tuberculosis Lineage Distribution in Xinjiang and Gansu Provinces, China.
Mycobacterium tuberculosis (M. tuberculosis) genotyping has dramatically improved the understanding of the epidemiology of tuberculosis (TB). In this study, 187 M. tuberculosis isolates from Xinjiang Uygur Autonomous Region (Xinjiang) and Gansu province in China were genotyped using large sequence polymorphisms (LSPs) and variable number tandem repeats (VNTR). Ten isolates, which represent major nodes of VNTR-based minimum spanning tree, were selected and subsequently subjected to multi-locus sequence analyses (MLSA) that include 82 genes. Based on a robust lineage assignment, we tested the association between lineages and clinical characteristics by logistic regression. There are three major lineages of M. tuberculosis prevalent in Xinjiang, viz. the East Asian Lineage 2 (42.1%; 56/133), the Euro-American Lineage 4 (33.1%; 44/133), and the Indian and East African Lineage 3 (24.8%; 33/133); two lineages prevalent in Gansu province, which are the Lineage 2 (87%; 47/54) and the Lineage 4 (13%; 7/54). The topological structures of the MLSA-based phylogeny support the LSP-based identification of M. tuberculosis lineages. The statistical results suggest an association between the Lineage 2 and the hemoptysis/bloody sputum symptom, fever in Uygur patients. The pathogenicity of the Lineage 2 remains to be further investigated.


Differential Association of HIV Funding With HIV Mortality by Race/Ethnicity, United States, 1999-2017.
Federal funds have been spent to reduce the disproportionate effects of HIV/AIDS on racial/ethnic minority groups in the United States. We investigated the association between federal domestic HIV funding and age-adjusted HIV death rates by race/ethnicity in the United States during 1999-2017. We analyzed HIV funding data from the Kaiser Family Foundation by federal fiscal year (FFY) and US age-adjusted death rates (AADRs) by race/ethnicity (Hispanic, non-Hispanic white, non-Hispanic black, and Asian/Pacific Islander and American Indian/Alaska Native [API+AI/AN]) from Centers for Disease Control and Prevention WONDER detailed mortality files. We fit joinpoint regression models to estimate the annual percentage change (APC), average APC, and changes in AADRs per billion US dollars in HIV funding, with 95% confidence intervals (CIs). For 19 data points, the number of joinpoints ranged from 0 to 4 on the basis of rules set by the program or by the user. A Monte Carlo permutation test indicated significant (P < .05) changes at joinpoints, and 2-sided t tests indicated significant APCs in AADRs. Domestic HIV funding increased from $10.7 billion in FFY 1999 to $26.3 billion in FFY 2017, but AADRs decreased at different rates for each racial/ethnic group. The average rate of change in AADR per US billion dollars was -9.4% (95% CI, -10.9% to -7.8%) for Hispanic residents, -7.8% (95% CI, -9.0% to -6.6%) for non-Hispanic black residents, -6.7% (95% CI, -9.3% to -4.0%) for non-Hispanic white residents, and -5.2% (95% CI, -7.8% to -2.5%) for non-Hispanic API+AI/AN residents. Increased domestic HIV funding was associated with faster decreases in age-adjusted HIV death rates for Hispanic and non-Hispanic black residents than for residents in other racial/ethnic groups. Increasing US HIV funding could be associated with decreasing future racial/ethnic disparities in the rate of HIV-related deaths.


Behavioral development following daily episodes of mother-infant separation in the rat.
Use of dermal or inhalation routes of maternal exposure during the postnatal period in rodent developmental neurotoxicity evaluations would be most practical if dams could be separated from their pups during the exposure period. However, this procedure raises questions concerning the effects of mother-infant separation itself on neurotoxicity endpoints. In the present study, Sprague-Dawley rat pups were either maternally deprived in warm incubators for 6 hr each day (7:00 AM-1:00 PM) or left with their dams (control), from Postnatal Day 4-20 (PND4-20), and were tested on a range of endpoints commonly used in developmental neurotoxicology. These included motor activity (PND13, 17, 19, 21, 29, 60), olfactory learning (PND18) and retention (PND25), T-maze delayed alternation (PND23, 24), acoustic startle response (PND23, 62), and auditory thresholds (PND62). None of the behavioral measures were affected by daily separation. Apparently, interrupting the mother-infant interaction for 6 hr/day has little or no effect by itself on behavioral development, as assessed by these measures.


Aggresomal sequestration and STUB1-mediated ubiquitylation during mammalian proteaphagy of inhibited proteasomes.
The 26S proteasome, a self-compartmentalized protease complex, plays a crucial role in protein quality control. Multiple levels of regulatory systems modulate proteasomal activity for substrate hydrolysis. However, the destruction mechanism of mammalian proteasomes is poorly understood. We found that inhibited proteasomes are sequestered into the insoluble aggresome via HDAC6- and dynein-mediated transport. These proteasomes colocalized with the autophagic receptor SQSTM1 and cleared through selective macroautophagy, linking aggresomal segregation to autophagic degradation. This proteaphagic pathway was counterbalanced with the recovery of proteasomal activity and was critical for reducing cellular proteasomal stress. Changes in associated proteins and polyubiquitylation on inhibited 26S proteasomes participated in the targeting mechanism to the aggresome and autophagosome. The STUB1 E3 Ub ligase specifically ubiquitylated purified human proteasomes in vitro, mainly via Lys63-linked chains. Genetic and chemical inhibition of STUB1 activity significantly impaired proteasome processing and reduced resistance to proteasomal stress. These data demonstrate that aggresomal sequestration is the crucial upstream event for proteasome quality control and overall protein homeostasis in mammals.


Exposure to sennoside-digoxin interaction and risk of digoxin toxicity: a population-based nested case-control study.
Digoxin is an important medication for heart failure (HF) patients and sennosides are widely used to treat constipation. Recently, safety concerns have been raised about a possible interaction between sennosides and digoxin, an issue that has not been studied empirically. This study therefore aimed to evaluate whether exposure to sennoside-digoxin interaction is associated with an increased risk of digoxin toxicity. This was a population-based nested case-control study that analysed data obtained from the Taiwan National Health Insurance Research Database between 1 January 2001 and 31 December 2004. All HF patients treated with digoxin for the first time were included as the study cohort. Of these, cases were identified as subjects hospitalized for digoxin toxicity (International Classification of Diseases, Ninth Revision, Clinical Modification, ICD-9-CM 972.1), and matched to randomly selected controls. Use of sennosides was compared between the two groups. Odds ratios (ORs) were employed to quantify the risk associated with exposure to sennoside-digoxin interaction by conditional logistic regression. The study cohort comprised 222,527 HF patients, of whom 524 were identified as cases and 2,502 as matched controls. Use of sennosides during the 14 days preceding the index date was found to be associated with a 1.61-fold increased risk of digoxin toxicity [95% confidence interval (CI) = 1.15, 2.25]. Additionally, a greater risk was observed for sennosides prescribed at an average daily dose ≥ 24 mg (adjusted OR = 1.93; 95% CI = 1.27, 2.94). The combined use of sennosides and digoxin was found to be associated with a modest increased risk of digoxin toxicity in HF patients.


Adjuvant therapy in breast cancer and venous thromboembolism.
Breast cancer patients are considered to be at relatively low risk of developing a TEE. The highest incidence of VTE events occurs in metastatic breast cancer patients likely due to extension of disease, immobility for pathologic bone fractures, cancer cachexia and venous compression by the tumour mass. Although thrombosis is less common in patients with early stage cancer compared to those with more advanced disease, it does occur and is clinically challenging. The adjuvant setting is of particular interest in order to assess the specific thrombogenic potential of systemic chemotherapy, because of the low tumor burden with only microscopic tumor foci at the time of treatment administration. This review summarizes risk factors, incidence and strategies to avoid VTE in breast cancer patients receiving adjuvant therapy.


Metabolism of immunoglobulin A, lymphocyte function, and histocompatibility antigens in patients on anticonvulsants.
Low serum IgA levels were found in patients taking phenytoin, together with evidence of depressed T cell function. There was no correlation between the dose or the serum level. A correlation was found, however, with HL-A status, patients with a low IgA showing increased frequency of HL-A2. It is suggested that epileptic patients with HL-A2 status are likely to develop IgA deficiency when given phenytoin.


Corrigendum to Shi M, Yu S, Ouyang Y, et al. Increased lifetime risk of ESRD in familial IgA nephropathy. Kidney Int Rep. 2021;6:91-100.
[This corrects the article DOI: 10.1016/j.ekir.2020.10.015.].


COVID-19 pandemic increases the occurrence of nursing burnout syndrome: an interrupted time-series analysis of preliminary data from 38 countries.
To evaluate the trends in nursing burnout rates before and during the coronavirus 2019 restrictions. Meta-analysis was used to extract the data on global nursing burnout from 1 Jan. 2010-15 Dec. 2022. An interrupted time-series analysis using segmented ordinary least squares (OLS) regression models was used to explore if the nursing burnout were affected by the epidemic. Newey-West standard error was used to adjust for autocorrelation and heteroskedasticity. Before the epidemic (April 2020), the nursing burnout rate rose with 0.0007497 (95% CI: 0.0000316, 0.0014677, t = 2.07, P = 0.041) per month. The trend of nursing burnout rate has increased by 0.0231042 (95 CI%:0.0086818, 0.0375266, t = 3.18, P = 0.002). The increasing trend of nursing burnout rate after the COVID-19 restrictions is 0.0007497 + 0.0231042 = 0.0238539 per month. The study indicated that the Covid-19 restrictions had an impact on nursing burnout, increasing the occurrence of nursing burnout syndrome.


Cost-effectiveness of pediatric norovirus vaccination in daycare settings.
Noroviruses are the leading cause of acute gastroenteritis in the United States and outbreaks frequently occur in daycare settings. Results of norovirus vaccine trials have been promising, however there are open questions as to whether vaccination of daycare children would be cost-effective. We investigated the incremental cost-effectiveness of a hypothetical norovirus vaccination for children in daycare settings compared to no vaccination. We conducted a model-based cost-effectiveness analysis using a disease transmission model of children attending daycare. Vaccination with a 90% coverage rate in addition to the observed standard of care (exclusion of symptomatic children from daycare) was compared to the observed standard of care. The main outcomes measures were infections and deaths averted, quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratio (ICER). Cost-effectiveness was analyzed from a societal perspective, including medical costs to children as well as productivity losses of parents, over a two-year time horizon. Data sources included outbreak surveillance data and published literature. A 50% efficacious norovirus vaccine averts 571.83 norovirus cases and 0.003 norovirus-related deaths per 10,000 children compared to the observed standard of care. A $200 norovirus vaccine that is 50% efficacious has a net cost increase of $178.10 per child and 0.025 more QALYs, resulting in an ICER of $7,028/QALY. Based on the probabilistic sensitivity analysis, we estimated that a $200 vaccination with 50% efficacy was 94.0% likely to be cost-effective at a willingness-to-pay of $100,000/QALY threshold and 95.3% likely at a $150,000/QALY threshold. Due to the large disease burden associated with norovirus, it is likely that vaccinating children in daycares could be cost-effective, even with modest vaccine efficacy and a high per-child cost of vaccination. Norovirus vaccination of children in daycare has a cost-effectiveness ratio similar to other commonly recommended childhood vaccines.


Potential mobilization of cadmium and zinc in soils spiked with smithsonite and sphalerite under different water management regimes.
Particulate cadmium (Cd) and zinc (Zn) are ubiquitous in agricultural soils of Pb-Zn mining regions. Water management serves as an important agronomic measure altering the bioavailability of Zn and Cd in soils, but how this affects particulate Cd and Zn and the underlying mechanisms remain largely unknown. Microcosm soil incubation combined with spectroscopic and microscopic characterization was conducted. During a two-year-long incubation period we observed that the concentrations of soil CaCl2-extractable Zn and Cd increased 3-10 times in sphalerite-spiked soils and 1-2 times in smithsonite-spiked soils under periodic flooding conditions due to the long-term dissolution of sphalerite (SP) and smithsonite (SM). However, the increase in the concentration of CaCl2-extractable metals (Zn: from 0.607 mg kg-1 to 1.051 mg kg-1 and Cd: from 0.047 mg kg-1 to 0.119 mg kg-1) was found only in SP-treatment under continuous flooding conditions, indicating the mobilization of metals. Ultrafiltration analysis shows that the nanoparticulate fraction of Zn and Cd in soil pore water increased 5 and 7 times in SP-treatments under continuous flooding conditions, suggesting the increment of metal pools in soil pore water. HRTEM-EDX-SAED further reveals that these nanoparticles were mainly crystalline ZnS and Zn-bearing sulfate nanoparticles in the SP-treatment and amorphous ZnCO3 and ZnS nanoparticles in the SM-treatment. Therefore, the formation of the stable crystalline Zn-bearing nanoparticles in the SP-treatment may explain the elevation of the concentration of soil CaCl2-extractable Zn and Cd under continuous flooding. The potential mobility of particulate metals should therefore be expected in scenarios of continuous flooding such as paddy soils and wetland systems.


Peroxisomal disorders in children: immunohistochemistry and neuropathology.
Immunohistochemical studies with antisera against four peroxisomal enzymes, catalase and beta-oxidation enzymes (acyl-coenzyme A oxidase, bifunctional protein, and 3-ketoacyl-CoA thiolase), were performed on brain, liver, and kidney specimens from patients with peroxisomal disorders, as well as specimens from three control subjects, by using conventional paraffin-embedded autopsy material. The patients included eight with Zellweger syndrome and one with neonatal adrenoleukodystrophy. In the liver and kidney specimens from all patients, except one with Zellweger syndrome, diffuse immunostaining with all antisera in the cytoplasm of hepatocytes and renal tubular epithelium suggested an absence of peroxisomes but the presence of peroxisomal enzymes. Examination of brain specimens indicated a weak or negative reaction of neurons in the cerebral cortex and a weak reaction of glial cells in the white matter, which suggested maturational delay compared with control subjects. The delayed immunoreactive pattern of peroxisomal enzymes in Zellweger syndrome and neonatal adrenoleukodystrophy may be related to the significant neuropathologic features of polymicrogyria and dysmyelinogenesis. One patient with Zellweger syndrome had a unique finding of a positive granular catalase reaction and a negative reaction with antisera to 3-ketoacyl-coenzyme A thiolase, which suggested a diagnosis of pseudo-Zellweger syndrome. This study validates the application of these immunohistochemical methods to the study of peroxisomal enzymes. Use of these methods improves the accuracy of diagnosis of peroxisomal disorders.


Pyrazolo[3,4-d]pyrimidines containing an extended 3-substituent as potent inhibitors of Lck -- a selectivity insight.
A series of para-substituted 3-phenyl pyrazolopyrimidines was synthesized and evaluated as inhibitors of lck. The nature of the substitution affected enzyme selectivity and potency for lck, src, kdr, and tie-2. The para-phenoxyphenyl analogue 2 is an orally active lck inhibitor with a bioavailability of 69% and exhibits an extended duration of action in animal models of T cell inhibition.


Characterization of the Quality Factor Due to the Static Prestress in Classical Caputo and Caputo-Fabrizio Fractional Thermoelastic Silicon Microbeam.
The thermal quality factor is the most significant parameter of the micro/nanobeam resonator. Less energy is released by vibration and low damping, which results in greater efficiency. Thus, for a simply supported microbeam resonator made of silicon (Si), a thermal analysis of the thermal quality factor was introduced. A force due to static prestress was considered. The governing equations were constructed in a unified system. This system generates six different models of heat conduction; the traditional Lord-Shulman, Lord-Shulman based on classical Caputo fractional derivative, Lord-Shulman based on the Caputo-Fabrizio fractional derivative, traditional Tzou, Tzou based on the classical Caputo fractional derivative, and Tzou based on the Caputo-Fabrizio fractional derivative. The results show that the force due to static prestress, the fractional order parameter, the isothermal value of natural frequency, and the beam's length significantly affect the thermal quality factor. The two types of fractional derivatives applied have different and significant effects on the thermal quality factor.


Changes of Urinary Cytokines in Non-Diabetic Obese Patients After Laparoscopic Sleeve Gastrectomy.
Adipose tissues synthesize and secrete various proinflammatory and anti-inflammatory mediators, termed cytokines. This work aims to assess different serum and urinary cytokine levels before and 12 months after laparoscopic sleeve gastrectomy (LSG). This prospective study was performed on 61 obese non-diabetic patients who underwent LSG. All patients were followed up postoperatively at 12 months with the assessment of arterial blood pressure, microalbuminuria, urinary and serum levels of inflammatory cytokines (macrophage migration inhibitory factor "MIF," monocyte chemotactic protein "MCP"-1, chemokine (C-C motif) ligand 15 (CCL-15), and CCL-18), in addition to serum creatinine, total cholesterol, and C-reactive protein (CRP). Mean BMI showed decreased substantially from 44.78 ± 3.59 Kg/m2 to 34.56 ± 2.45. Systolic blood pressure decreased from 147.03 ± 16.89 mmHg to 128.82 ± 12.52 and diastolic blood pressure decreased from 90.51 ± 12.71 mmHg to 79.69 ± 10.39. At one-year of follow-up, there was statistically significant decrease of mean serum creatinine, total cholesterol, CRP, CCL-15, CCL-18, MIF/creatinine ratio, MCP-1/creatinine ratio, CCL-15/creatinine ratio, and CCL-18/creatinine ratio (P value <0.001). Improvement of systemic and renal inflammatory states after LSG may positively affect obesity-related renal disease by steering the adipokine levels towards anti-inflammatory profiles.


Respiratory Viral Shedding in Healthcare Workers Reinfected with SARS-CoV-2, Brazil, 2020.
We documented 4 cases of severe acute respiratory syndrome coronavirus 2 reinfection by non-variant of concern strains among healthcare workers in Campinas, Brazil. We isolated infectious particles from nasopharyngeal secretions during both infection episodes. Improved and continued protection measures are necessary to mitigate the risk for reinfection among healthcare workers.


Uridine-based paramagnetic supramolecular nanoaggregate with high relaxivity capable of detecting primitive liver tumor lesions.
The water soluble uridine-based paramagnetic self-assembled amphiphilic molecules (LGd2-5) with DTTA binding site were synthesized and have been characterized in regard to their T(1) magnetic resonance imaging (MRI) contrast agent (CA) properties. The water proton relaxivities have been measured in phosphate buffered saline (PBS) at 36 °C at 3 different magnetic fields. Among the self-assembled CAs, LGd3 showed unprecedented, high relaxivities of 30.3 and 23.4 mM(-1) s(-1) in PBS solution at 36 °C at 0.47 and 1.41 T, respectively. The non-covalent interactions between the new CAs and human serum albumin (HSA) have been investigated and the relaxivity was further increased by 135-215% depending on alkyl chain lengths. The chemically inertness of these complexes (LGd1, LGd2, LGd3, LGd4) against biologically most abundant metal ion (i.e. Zn(2+)) have shown within the range of commercial DTPA-based CAs. In vivo pharmacokinetics of the complex LGd3 showed highly specific for hepatocytes resulting in increase of contrast noise ratio by ∼240% in T(1)-weighted MR images of mouse liver 2 h after injection of the LGd3. It is capable to detect small hepatocellular carcinoma (HCC) with diameter of 1.5 mm.


Prevention of arrhythmias by flecainide after noncardiac thoracic surgery.
Cardiac arrhythmias are a frequent complication after thoracic operations. The prophylactic value of flecainide administered as a constant-rate, intravenous infusion (0.15 mg/kg/h) after a loading dose (2 mg/kg) was tested in a randomized, placebo-controlled study in 30 patients using Holter monitoring during the first 72 hours after operation. A high incidence of atrial and complex ventricular arrhythmias was observed in the placebo-treated group, with a clear predominance in patients undergoing left thoracotomy. Antiarrhythmic drugs had to be added in 6 patients in the placebo-treated group (n = 16), but in none in the flecainide-treated group (n = 14) (p less than 0.01). The preventive effect of flecainide was observed at serum concentrations in the middle of the therapeutic range (409 ng/mL) without side effects. It is concluded that flecainide administration effectively reduced or prevented cardiac arrhythmias after thoracic operations.


Mortalin is over-expressed by colorectal adenocarcinomas and correlates with poor survival.
Using comparative proteomic analysis we have identified over-expression of mortalin in colorectal adenocarcinomas. Mortalin, also known as mitochondrial heat-shock protein 70 (mhsp 70), is involved in cell cycle regulation with important roles in cellular senescence and immortalization pathways. It is known to bind to and inactivate wild-type tumour suppressor protein p53 and influences the Ras-Raf-MAPK pathway. By immunostaining a colorectal cancer tissue microarray linked to a patient database, we further found that mortalin over-expression correlates with poor patient survival and, in multivariate analysis, is independent of standard prognostic variables (p = 0.04). Our findings demonstrate that mortalin over-expression may predict outcome in colorectal cancer and suggest that this protein is involved in colorectal neoplasia. Our experimental approach emphasises the analytical power of combining proteomics with tissue microarray analysis in the context of a well-defined tumour database.


Educating Health Science Students About Peace through Health Topic; A Panel Discussion.
This report describes an experience of the first international health for peace conference held in November 2018 in Shiraz University of Medical Sciences. This paper discusses the panel on peace education in medical and paramedical schools and the way for the future.


Antecedent anti-NMDA receptor encephalitis in two patients with multiple sclerosis.
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder characterised by psychiatric symptoms, movement disorder and seizures often evolving into a severe encephalopathy. An overlap has recently been recognised between anti-NMDAR encephalitis and inflammatory demyelinating disorders, particularly neuromyelitis optical spectrum disorder (NMOSD). In this case report, we describe two patients with an initial presentation consistent with anti-NMDAR encephalitis who have subsequently developed relapsing-remitting multiple sclerosis (MS) and discuss the literature pertaining to potential overlap between NMDAR encephalitis and inflammatory demyelinating disorders.


Distributed structure determination at the JCSG.
The Joint Center for Structural Genomics (JCSG), one of four large-scale structure-determination centers funded by the US Protein Structure Initiative (PSI) through the National Institute for General Medical Sciences, has been operating an automated distributed structure-solution pipeline, Xsolve, for well over half a decade. During PSI-2, Xsolve solved, traced and partially refined 90% of the JCSG's nearly 770 MAD/SAD structures at an average resolution of about 2 Å without human intervention. Xsolve executes many well established publicly available crystallography software programs in parallel on a commodity Linux cluster, resulting in multiple traces for any given target. Additional software programs have been developed and integrated into Xsolve to further minimize human effort in structure refinement. Consensus-Modeler exploits complementarities in traces from Xsolve to compute a single optimal model for manual refinement. Xpleo is a powerful robotics-inspired algorithm to build missing fragments and qFit automatically identifies and fits alternate conformations.


Paclitaxel Induce Apoptosis of Giant Cells Tumor of Bone via TP53INP1 Signaling.
To evaluate the antitumor capability and to investigate the underlying molecular mechanism of paclitaxel. First, cck-8 and apoptosis assays were used to determine survival and apoptotic effects of HS 737.T cells under treatment of paclitaxel. Next, RNA-seq and bioinformatics were used to determine the differentially expressed genes and to analyze the pathway involved. Quantitative real-time polymerase chain reaction was used to verify the accuracy of some differentially expressed genes (DEG). ClueGO was used to decode and visualize functionally grouped GO terms of differentially expressed genes, and to map the DEG protein-protein interactions (PPI) network. Western blotting was used to check the expression of target genes, the cleavage of Caspase-3 and PARP1, and the phosphorylation level of p53. Finally, transcriptomics, bioinformatics, and RNAi were used to estimate the antitumor capability and to identify the underlying mechanisms of paclitaxel in GCTB. Our data revealed that paclitaxel had significant time-dependent effects on the viability and induced apoptosis of HS 737.T cells. RNA-seq and bioinformatics analysis showed that apoptosis, death receptor signaling pathway, TNF signaling pathway, and TP53 regulated transcription of cell death genes pathway were closely associated with paclitaxel in the treatment of GCTB. Western bolt results revealed that paclitaxel induced cleavage of Caspase-3 and PARP1, and increased the phosphorylation level of p53 in HS 737.T cells. RNAi results showed that the expression level of TP53INP1 was significantly decreased in HS737.T cells (the decrease was more than 70%). In addition, we found that the inhibitory ratios of paclitaxel on HS737.T cells deficient in TP53INP1 were less than in HS737.T cells with empty vector (19.88 and 40.60%, respectively). Hence, our data revealed that TP53INP1 regulated paclitaxel-driven apoptosis in HS737.T cells. Paclitaxel can significantly repress cell proliferation and induce apoptosis of HS 737.T cells through activating Caspase-3, PARP1, p53, and TP53INP1. Paclitaxel may be an effective drug in the management of GCTB.


Noninvasive high-frequency oscillations riding spikes delineates epileptogenic sources.
High-frequency oscillations (HFOs) are a promising biomarker for localizing epileptogenic brain and guiding successful neurosurgery. However, the utility and translation of noninvasive HFOs, although highly desirable, is impeded by the difficulty in differentiating pathological HFOs from nonepileptiform high-frequency activities and localizing the epileptic tissue using noninvasive scalp recordings, which are typically contaminated with high noise levels. Here, we show that the consistent concurrence of HFOs with epileptiform spikes (pHFOs) provides a tractable means to identify pathological HFOs automatically, and this in turn demarks an epileptiform spike subgroup with higher epileptic relevance than the other spikes in a cohort of 25 temporal epilepsy patients (including a total of 2,967 interictal spikes and 1,477 HFO events). We found significant morphological distinctions of HFOs and spikes in the presence/absence of this concurrent status. We also demonstrated that the proposed pHFO source imaging enhanced localization of epileptogenic tissue by 162% (∼5.36 mm) for concordance with surgical resection and by 186% (∼12.48 mm) with seizure-onset zone determined by invasive studies, compared to conventional spike imaging, and demonstrated superior congruence with the surgical outcomes. Strikingly, the performance of spike imaging was selectively boosted by the presence of spikes with pHFOs, especially in patients with multitype spikes. Our findings suggest that concurrent HFOs and spikes reciprocally discriminate pathological activities, providing a translational tool for noninvasive presurgical diagnosis and postsurgical evaluation in vulnerable patients.


Long-term effects of young-adult methamphetamine on dorsal raphe serotonin systems in mice: Role of brain-derived neurotrophic factor.
To assess the long-term effects of chronic adolescent methamphetamine (METH) treatment on the serotonin system in the brain, we used serotonin-1A receptor (5-HT1A) and serotonin transporter (SERT) autoradiography, and quantitative tryptophan-hydroxylase 2 (TPH2) immunohistochemistry in the raphe nuclei of mice. Because of the modulatory role of brain-derived neurotrophic factor (BDNF) on the serotonin system and the effects of METH, we included both BDNF heterozygous (HET) mice and wildtype (WT) controls. Male and female mice of both genotypes were treated with an escalating METH dose regimen from the age of 6-9 weeks. At least two weeks later, acute locomotor hyperactivity induced by a 5 mg/kg D-amphetamine challenge was significantly enhanced in METH-pretreated mice, showing long-term sensitisation. METH pretreatment caused a small, but significant decrease of 5-HT1A receptor binding in the dorsal raphe nucleus (DRN) of males independent of genotype, but there were no changes in the median raphe nucleus (MRN) or in SERT binding density. METH treatment reduced the number of TPH2 positive cells in ventral subregions of the rostral and medial DRN independent of genotype. METH treatment selectively reduced DRN cell counts in BDNF HET mice compared to wildtype mice in medial and caudal ventrolateral subregions previously associated with panic-like behaviour. The data increase our understanding of the long-term and selective effects of METH on brain serotonin systems. These findings could be relevant for some of the psychosis-like symptoms associated with long-term METH use.


Advancing interprofessional education in communication.
The objective of this training project is to develop and host Interprofessional Communication courses to improve interdisciplinary communication in oncology care. The initial national course was held in a virtual format and included pre- and post-course participant data. The curriculum was developed with support from the National Cancer Institute. A virtual two-day course was held to equip nurses, social workers, and chaplains with vital communication skills in oncology practice, so that they could return to their home institutions and teach communication skills to other healthcare professionals, with the intention of making improved communication a quality improvement goal. Fifty-two participants were selected through an application process to attend the virtual course in two-person interprofessional teams (e.g., nurse and chaplain, or social worker and nurse). The Interprofessional Communication Curriculum was based on the National Consensus Project for Quality Palliative Care's eight domains of quality palliative care. The six online modules developed by the investigators were presented in lectures, supplemented by discussion groups, role plays, and other methods of experiential learning. Pre- and post-course results identified areas of communication, which are a priority for improvement by oncology clinicians. Participant goals identified specific strategies to be implemented by participants in their settings. The need for communication training was clearly demonstrated across professions in this national training course. Participants were able to apply course content to their goals for quality improvement in cancer settings.


Absence of analgesic effect of intravenous melatonin administration during daytime after laparoscopic cholecystectomy: a randomized trial.
To investigate whether melatonin administered intraoperatively reduced pain following laparoscopic cholecystectomy. Randomized, placebo-controlled, double-blinded study. Two surgical departments in Copenhagen. 44 women between 18 and 70 years of age, who were surgical candidates for laparoscopic cholecystectomy. Patients were anesthetized by a standard protocol and received a standard multimodal postoperative analgesic regimen. Patients undergoing surgery were admitted on the day of surgery and were discharged the day after surgery. Ten mg of intravenous (IV) melatonin or placebo were administered at the time of surgical incision. Pain was assessed by a set of questionnaires documenting "pain at rest" using a visual analog scale (VAS). The use of rescue medication was recorded. Sleep quality and general well-being were measured on separate VAS scales. Sleepiness was assessed by the Karolinska Sleepiness Scale. Forty-four patients were included and randomized to the study. Three patients did not complete the study. No differences in VAS pain scores, sleep quality, general well-being, or sleepiness were found between the two groups in the postoperative period. The use of postoperative rescue medication did not differ between the groups. The use of 10mg of IV melatonin administered during laparoscopic cholecystectomy did not affect postoperative pain or use of analgesic medication.


Electron microscopic studies on the formation of vesicular bodies during cell wall degradation and regeneration in yeast.
Vesicular bodies are observed during enzymatic degradation of the yeast cell wall and in the course of wall regeneration. In both cases various types of vesicles are formed and exocytated by different mechanisms. They are characterized cytochemically and their possible role in cell wall regeneration is discussed.


The white water of change. A survivor's guide.
Managing in an environment of fast, continuous change requires a special perspective and skill set. This article describes a systems framework for understanding the forces behind the turbulence and develops approaches to managing in a dynamically complex environment. Building on this background, five principles guide nurse managers to stay on top of change and thrive in turbulent times.


EVALUATION OF OPTIC DISK AND MACULAR VASCULARITY CHANGES IN CRVO USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.
To quantify changes in optic disk and macular vasculature in patients with central retinal vein occlusion using optical coherence tomography angiography and detect its correlation with visual acuity. The study included 20 eyes of 20 patients with treatment-naive central retinal vein occlusion and 20 age-matched controls. Optical coherence tomography and optical coherence tomography angiographywere performed on the macula and optic disk. Central 1-mm subfield foveal thickness was measured. Vessel densities (VD) of superficial and deep macular capillary plexuses with whole disk VD, inside disk VD, and radial peripapillary capillary plexus were analyzed. Macular ischemia was evaluated by fundus fluorescein angiography. Visual acuity was correlated with measured parameters. All measured macular and disk VDs differed significantly between cases and controls except inside disk VD. Visual acuity showed a highly significant negative correlation with whole disk VD ( P = 0.005) and radial peripapillary capillary ( P = 0.002), borderline correlation with central subfield foveal thickness ( P = 0.06), and insignificant correlation with macular VDs. Radial peripapillary capillary VD showed a significant correlation with deep parafoveal ( P = 0.04), and superficial and deep perifoveal VDs ( P = 0.01). Optic disk VD could provide more accurate indication of retinal blood supply than macular VD in cases of central retinal vein occlusion with severe macular edema.


Roux-en-Y gastric bypass contributes to weight loss-independent improvement in hypothalamic inflammation and leptin sensitivity through gut-microglia-neuron-crosstalk.
Hypothalamic inflammation and endoplasmic reticulum (ER) stress are extensively linked to leptin resistance and overnutrition-related diseases. Surgical intervention remains the most efficient long-term weight-loss strategy for morbid obesity, but mechanisms underlying sustained feeding suppression remain largely elusive. This study investigated whether Roux-en-Y gastric bypass (RYGB) interacts with obesity-associated hypothalamic inflammation to restore central leptin signaling as a mechanistic account for post-operative appetite suppression. RYGB or sham surgery was performed in high-fat diet-induced obese Wistar rats. Sham-operated rats were fed ad libitum or by weight matching to RYGB via calorie restriction (CR) before hypothalamic leptin signaling, microglia reactivity, and the inflammatory pathways were examined to be under the control of gut microbiota-derived circulating signaling. RYGB, other than CR-induced adiposity reduction, ameliorates hypothalamic gliosis, inflammatory signaling, and ER stress, which are linked to enhanced hypothalamic leptin signaling and responsiveness. Mechanistically, we demonstrate that RYGB interferes with hypothalamic ER stress and toll-like receptor 4 (TLR4) signaling to restore the anorexigenic action of leptin, which most likely results from modulation of a circulating factor derived from the altered gut microbial environment upon RYGB surgery. Our data demonstrate that RYGB interferes with hypothalamic TLR4 signaling to restore the anorexigenic action of leptin, which most likely results from modulation of a circulating factor derived from the post-surgical altered gut microbial environment.


The Role of Obesity in Preeclampsia.
The incidence of obesity is increasing at an alarming rate. There is compelling evidence that obesity increases the risk of preeclampsia about 3-fold, and in developed countries is the leading attributable risk for the disorder. In this presentation we explore this relationship and propose targets for future studies guided by the much more extensively studied relationship of obesity to cardiovascular disease. We further address the hypothesis that asymmetric dimethyl arginine (ADMA), an endogenous inhibitor of nitric oxide synthase, may be one convergence point for the mechanism by which obesity increases the risk of preeclampsia. We conclude with consideration of the clinical implications of this information.


Visual perspective taking by dogs (Canis familiaris) in a Guesser-Knower task: evidence for a canine theory of mind?
We tested domestic dogs (N = 16) in a Guesser-Knower task in which they chose between possible locations for hidden food indicated by human informants. In four experiments, the perceptual access of the Guesser and Knower to the hidden food baiting was manipulated. When informants had differing perceptual access to the baiting, dogs preferred the location indicated by the Knower from the start of testing (Experiment 1), even when baiting was done by a third experimenter (Experiments 2-3). However, when there was no difference in perceptual access and both informants either knew or did not know the food location, dogs had no preference between the informants (Experiment 4). Controls ruled out alternative explanations in terms of associative learning, unintentional and olfactory cues. Analysis of individual data showed no significant heterogeneity across dogs, and results were not correlated with age or sex. Dogs' performances were superior to those of nonhuman primates in previous studies. Although a mentalistic explanation is not required, results add to evidence that dogs have a remarkable sensitivity to cues related to humans' attentional state, which enables them to respond as if they had a functional theory of mind in the Guesser-Knower task with human informants.


Mesenchymal stem cells act as stimulators of neurogenesis and synaptic function in a rat model of Alzheimer's disease.
Alzheimer's disease (AD) is one of the most common NDs leading to cognitive dysfunctions and dementia which are progressively worsen with age. Cell therapy is currently of particular interest in treatment of neurodegenerative disease (ND) such as AD. However, the effective treatment for AD is yet to be found. In this study, the possible roles of human umbilical mesnchymal stromal cord (hUMSCs) and adipose mesenchymal stem cells (hAD-MSCs) in neurogenesis and synaptic function were investigated using a β-amyloid 1-42 (β A42)-induced AD rat model. hUMSCs and hAD-MSCs were isolated from umbilical cord stroma and adipose tissue, respectively. The expression of Mesenchymal (CD73, CD90 and CD105) and hematopoietic (CD45 and CD133) markers of hUMSCs and hAD-MSCs were confirmed by flow cytometry. Alzheimer's rat model was created by β-amyloid 1-42 injection into the hippocampus and confirmed by Morris Water Maze and immunohistochemical staining. hUMSCs and hAD-MSCs were injected in Alzheimer's rat model, intravenously. Deposition of β-amyloid in the CA1 of hippocampus was assayed 3 months after cell administration. The expression of synaptophysin and GAP43 proteins was assessed by Western blot. Neural death was assessed by Nissl staining. The data obtained from flow cytometry showed that surface mesenchymal and hematopoteic markers of the fibroblastic like cells isolated from adipose tissue and umbilical cord were expressed highly in hUMSCs and mostly in hAD-SCs. Transplantation of MSCs reduced β-amyloid deposition in the hippocampus of the AD rats compared to the β-amyloid group. The rate of neuronal cell death in the hippocampus of the β-amyloid-treated rats was significantly increased compared to that of the control group. The percentage of apoptotic cells in this group was 72.98 ± 1.25, which was significantly increased compared to the control group. Transplantation of either hUMSCs or hAD-SCs, respectively, resulted in a significant reduction in the apoptotic rate of the neuronal cells in the hippocampus by 39.47 ± 0.01 (p = 0.0001) and 43.23 ± 0.577 (p = 0.001) compared to the β-amyloid group. MSC transplantation resulted in a significant up-regulation in the expression levels of both synaptogenic (synaptophysin) and neurogenic markers (GAP43) by 1.289 ± 0.112 (P = 0.02) and 1.112 ± 0.106 (P = 0.005) fold in the hUMSCs-treated group and 1.174 ± 0.105 (P = 0.04) and 0.978 ± 0.167 (P = 0.008) fold in the hAD-SCs-treated group, respectively. Intravenous injection of hUMSCs and hAD-MSCs is a safe approach that improves synaptic function and neurogenesis via up-regulation of synaptophysin and GAP43 protein expression levels, respectively, in Alzheimer's model. Intravenous injection of both applied SCs could improve learning and cognitive impairment induced by β A42 injection.


Thrombolysis or peripheral arterial surgery: phase I results. TOPAS Investigators.
Thrombolytic therapy is widely used in the treatment of peripheral arterial occlusion, but prospective, randomized comparisons with standard therapy remain few. A multicenter trial of thrombolysis or peripheral arterial surgery (TOPAS) was organized to compare critically the use of recombinant urokinase (rUK) or surgery for the initial treatment of acute lower-extremity ischemia. Phase I of the trial was designed as a dose-ranging trial to evaluate the safety and efficacy of three doses of rUK in comparison with surgery. In a multicenter, prospective, double-blind comparison, 213 patients who had acute lower-extremity ischemia for 14 days or fewer were randomized to one of two groups. The first group received one of three dosages of rUK (catheter-directed at 2000, 4000, or 6000 IU/min for 4 hours, then 2000 IU/min to a maximum of 48 hours). The second group underwent surgery. Successful thrombolysis was followed by surgical or endovascular interventions when anatomic lesions responsible for the occlusion were unmasked. Patients were followed-up for 1 year; data were evaluated on an intent-to-treat basis. The 4000 IU/min rUK dosage was chosen as the most appropriate thrombolytic regimen because it maximized lytic efficacy against the risk of bleeding. Complete (> 95%) lysis of thrombus was achieved in 71% of the 49 patients who were randomized to the 4000 IU/min group, with a mean infusion time of 23 hours. In contrast, complete lysis was achieved in 67% of patients who received 2000 IU/min and in 60% of patients who received 6000 IU/min. Hemorrhagic complications occurred in 2% of the 4000 IU/min group versus 13% of the 2000 IU/min group (p = 0.05) and 16% of the 6000 IU/min group (p = 0.03). In a comparison of the 4000 IU/min group with the surgical group, the 1-year mortality rate (14% vs 16%) or amputation-free survival rate (75% vs 65%) did not differ significantly. The frequency and magnitude of surgery in the patients randomized to rUK were decreased (p < 0.001). The preliminary results suggest that an initial rUK dose of 4000 IU/min is safe and efficacious in the treatment of acute lower-extremity ischemia. rUK therapy is associated with limb salvage and patient survival rates similar to those achieved with surgery, concurrent with a reduced requirement for complex surgery after thrombolytic intervention.


Duodenal morphology and intensity of infection in AIDS-related intestinal cryptosporidiosis.
The pathogenesis of intestinal cryptosporidiosis is not known. Previous studies have shown that the intensity of infection varies between patients. The hypothesis of this study is that intestinal injury is related to the intensity of infection. The histological abnormalities associated with Cryptosporidium infection were evaluated in duodenal biopsy specimens from 18 patients with acquired immunodeficiency syndrome-associated cryptosporidiosis. The intensity of Cryptosporidium infection was assessed histologically in all patients as the percentage of mucosa covered by organisms and by quantitation of oocyst excretion in the stools of 14 patients. Duodenal biopsy specimens from 13 patients (72%) showed normal villous architecture. In these patients, the inflammatory component of the lamina propria was either normal or moderately increased. This increase consisted mostly of lymphocytes and plasma cells. Five of 18 patients (28%) had flattening of the mucosa associated with a prominent neutrophilic infiltrate. The intensity of infection in patients with villous flattening as measured from biopsy specimens and stool was significantly higher than in those without flattening (92% vs. 12% mucosa occupied with organisms; 738 x 10(3) vs. 199 x 10(3) oocyst/mL stool) (P < 0.004 in both cases). Most patients with intestinal Cryptosporidium infection had normal duodenal villous architecture. Severe duodenal morphological abnormalities, including flattening of the villi, were associated with high-intensity infections.


Update on Hodgkin lymphoma from a radiologist's perspective.
Recent advances in the management of Hodgkin lymphoma, due to new staging and response assessment systems as well as new therapies, have redefined the role of imaging for this disease. The purpose of this article is to provide radiologists with an update on the current role of imaging in Hodgkin lymphoma from diagnosis to assessment of treatment response, in view of the new staging and response assessment system and current treatment strategies.


Osteoporosis guideline awareness among Iranian nurses: results of a knowledge and attitudes survey.
Osteoporosis is a chronic and progressive disease associated with gradual bone loss and elevated risk of fracture. Role of health care professional especially nurses in lowering burden of osteoporosis via patients and public education is critical. Current study conducted to evaluate knowledge and attitude regarding osteoporosis among the nurses in orthopedic wards and their experience with national clinical osteoporosis guideline. A cross-sectional study was conducted from August to December 2016 among all nurses in orthopedic ward of hospitals affiliated to Shiraz University of Medical Sciences. The 23- item self-administered scale consisted of knowledge and attitude questions were used. Moreover, data regarding participation in osteoporosis training courses and awareness of the national osteoporosis clinical guideline were collected as a measure of nurses' experience with guideline. The gathered data were analyzed using SPSS (V. 16), student t-test was used to compare total knowledge and attitude scores between categorical demographic and professional data. Pearson test was used to calculate the correlation between total knowledge and attitude scores and years of practice. A p-value < 0.05 was considered statistically significant. From total of 160 nurses, 143 of them completed the questionnaire (response rate: 89.3%). The total mean ± SD knowledge and attitude scores were 11.60 ± 3.10 and 3.47 ± 0.92 respectively. Six nurses (4.2%) had participated in osteoporosis training courses after graduation, and 39 (27.3%) had been aware of the national osteoporosis clinical guideline. Knowledge and attitude scores among nurses who practice in private hospitals was higher than those practices in the teaching hospitals. These differences were statistically significant based on student t-test. According to Pearson correlation coefficient, there was positive and significant correlation between nurses' knowledge and attitude score (Correlation coefficient: 0.199, p-value = 0.037). Our findings reveal that nurses' knowledge and attitude regarding osteoporosis was not satisfactory. Most of them were not aware of national osteoporosis clinical guideline and had not participated in osteoporosis training courses after their graduation. We need more empowered nurses to lowering burden of osteoporosis and its consequences in the future.


Dynamics of Patient-Based Benefit-Risk Assessment of Medicines in Chronic Diseases: A Systematic Review.
A critical gap exits in understanding the dynamics of patient-based benefit-risk assessment (BRA) of medicines in chronic diseases during the disease journey. To systematically review and synthesize current evidence on the changes of patients' preferences about the benefits and risks of medicines during their disease journey including the influence of disease duration and severity, and previous treatment experience. A systematic review of studies identified in PubMed and Embase, from inception to November 2020, was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Articles were eligible if they analyzed adult patient-based BRA of medicines with a chronic disease, based on at least one of the pre-specified dimensions: disease severity, disease duration, or previous treatment experience. A total of 26,228 articles were identified and 105 were eligible for inclusion. Of these, 85 detected a variation in patient-based BRA of medicines with at least one of the pre-specified criteria. Patients with higher disease severity and more treatment experience have increased risk tolerance. It remains inconclusive whether disease duration directly affects the relative importance of a patient's preference. Factors important for patients' BRA of their medicines during a chronic disease journey vary more with their clinical situation and previous treatment experience than with time since diagnosis. Due to the importance of these factors on patients' perspectives and potential impact on their decision-making and eventually their clinical outcomes, there is a need for more studies to assess the dynamics of patients' BRA in every disease.


[Ventricular septal defect with aortic failure (Laubry and Pezzi syndrome). Surgical indications and results. Apropos of 20 cases].
The association of aortic incompetence and ventricualr septal defect is rare, but justifies the regular supervision of all patients with VSD. It seems to be found more commonly in cases where the VSD is above the crista. Early operation appears to be justified, and in a large number of cases this avoids the progressive worsening of the aortic incompetence; this in turn leads to better results with the conservative surgical procedures.


Impact of the COVID-19 pandemic on Australian community health service staff's occupational and personal lives: a longitudinal study.
Little is known about the impact of the coronavirus disease 2019 (COVID-19) pandemic on community health service staff. The aim of this study was to assess the immediate and longer-term psychosocial impacts of COVID-19 on community health service staff in Australia. A prospective cohort design with an anonymous cross-sectional online survey that was administered at two time points (March-April 2021; n =681 and September-October 2021; n =479). Staff (clinical and non-clinical) were recruited from eight community health services in Victoria, Australia. Study-specific questions evaluated the impact of COVID-19 on respondents' work and personal lives. Space was provided at the end of the surveys for free-text comments. There were no significant differences in respondent characteristics between the two surveys. At both survey time points, respondents were mostly concerned about their family's health. Compared to the first survey, survey two respondents were significantly more likely to report concerns about infecting family members (48.8% vs 41.6%, P =0.029), clients having COVID-19 (43.2% vs 36.2%, P =0.035), getting COVID-19 at work (53.7% vs 45.6%, P =0.014), not being prepared to care for clients with COVID-19 (27.5% vs 18.8%, P =0.006) and feeling more stress at work (63.7% vs 50.8%, P P =0.026). The COVID-19 pandemic has had a considerable impact on the work and personal lives of community health service staff. Staff would benefit from continued and targeted initiatives that address their wellbeing and concerns.


Response mechanism of microbial community during anaerobic biotransformation of marine toxin domoic acid.
Domoic acid (DA) is a potent neurotoxin produced by toxigenic Pseudo-nitzschia blooms and quickly transfers to the benthic anaerobic environment by marine snow particles. DA anaerobic biotransformation is driven by microbial interactions, in which trace amounts of DA can cause physiological stress in marine microorganisms. However, the underlying response mechanisms of microbial community to DA stress remain unclear. In this study, we utilized an anaerobic marine DA-degrading consortium GLY (using glycine as co-substrate) to systematically investigate the global response mechanisms of microbial community during DA anaerobic biotransformation.16S rRNA gene sequencing and metatranscriptomic analyses were applied to measure microbial community structure, function and metabolic responses. Results showed that DA stress markedly changed the composition of main species, with increased levels of Firmicutes and decreased levels of Proteobacteria, Cyanobacteria, Bacteroidetes and Actinobacteria. Several genera of tolerated bacteria (Bacillus and Solibacillus) were increased, while, Stenotrophomonas, Sphingomonas and Acinetobacter were decreased. Metatranscriptomic analyses indicated that DA stimulated the expression of quorum sensing, extracellular polymeric substance (EPS) production, sporulation, membrane transporters, bacterial chemotaxis, flagellar assembly and ribosome protection in community, promoting bacterial adaptation ability under DA stress. Moreover, amino acid metabolism, carbohydrate metabolism and lipid metabolism were modulated during DA anaerobic biotransformation to reduce metabolic burden, increase metabolic demands for EPS production and DA degradation. This study provides the new insights into response of microbial community to DA stress and its potential impact on benthic microorganisms in marine environments.


What does Arabidopsis natural variation teach us (and does not teach us) about adaptation in plants?
Sessile organisms such as plants have to develop adaptive responses to face environmental change. In Arabidopsis thaliana populations, natural variation for stress responses have been observed at different levels of integration and the genetic bases of those variations have been analysed using two strategies: classical linkage and association (LD) mapping. The strength of Arabidopsis resides in the huge amount of genomic data and molecular tools available leading to the identification of many polymorphisms responsible for phenotypic variation. Remaining limitations to clearly understand how Arabidopsis adapts to its environment, that is the complexity of the genetic architecture and the lack of ecological data, should be partially solved thanks to the development of new methods and the acquisition of new data.