Relation of Cardiac Dysfunction to Rhythm Abnormalities in Patients With Duchenne or Becker Muscular Dystrophies.
The association between systolic cardiac dysfunction and arrhythmia development in patients with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD) is generally assumed but has not been extensively studied. The purpose of this study was to describe arrhythmias in patients with DMD and BMD in the present era and determine whether arrhythmia development is associated with cardiac dysfunction. This is a single-center retrospective review of 237 Holters from 91 patients with DMD (mean = 17 ± 4 years, range 3 to 27 years) and 64 Holters from 21 patients with BMD (mean = 18 ± 7 years, range 4 to 31 years) with corresponding echocardiography. Holters were stratified by age of patient at the time of study and ejection fraction: normal (≥55%), mild (<55% and ≥45%), moderate (<45% and ≥30%), and severe (<30%). Arrhythmias included frequent atrial and ventricular premature complexes (>10/hr), couplets, and runs of supraventricular and ventricular tachycardias. Arrhythmias occurred in 44% of DMD and 57% of BMD patients and were significantly associated with decrease in cardiac function. Clinically significant arrhythmias (supraventricular tachycardia and ventricular tachycardia) occurred in 10% of all Holters obtained in patients with DMD and 25% of all Holters obtained in patients with BMD. Subgroup analysis of Holters from patients with DMD demonstrated that arrhythmias increased with decreasing ejection fraction regardless of age, but that age was also a significant predictor of arrhythmia development. In conclusion, among patients with DMD or BMD, arrhythmias increase with development of cardiac dysfunction.


[Relationship between cystatin C and coronary artery calcification in patients with intermediate cardiovascular risk].
Cardiovascular disease is the leading cause of morbimortality in industrialized countries. Quantification of coronary artery calcium (CAC) has been shown to have an independent and incremental prognostic value over traditional risk factors for the prediction of mortality and cardiovascular events. The aim of our study was to determine the possible relationship between CAC and cystatin C (CTC). We included 104 patients with stable chest pain, free of cardiovascular disease and nephropathy, with intermediate cardiovascular risk. Both CAC (Agatston) and CTC were determined. CTC was independently associated with the CAC level and the presence of coronary disease. CTC values may be associated with CAC and coronary disease. Further studies are needed to know the importance of these markers in clinical practice.


Heavy metal bioaccumulation by wild edible saprophytic and ectomycorrhizal mushrooms.
Heavy metals cause serious problems in the environment, and they can be accumulated in organisms, especially in the higher fungi. The concentration of Ni, Cr, Pb, Cd, and Hg in 10 species of edible mushrooms in Medvednica Nature Park, Croatia was therefore determined. In addition, the similarity between the studied species was determined by cluster analysis based on concentrations of the aforementioned metals in the fruiting bodies. The contents of nickel, chromium, lead, cadmium, and mercury in the fruiting bodies of mushrooms were obtained by X-ray fluorescence spectrometry. The highest concentrations of Ni (3.62 mg kg(-1)), Cr (3.01 mg kg(-1)), and Cd (2.67 mg kg(-1)) were determined in Agaricus campestris. The highest concentration of Pb (1.67 mg kg(-1)) was determined in Macrolepiota procera, and the highest concentration of Hg (2.39 mg kg(-1)) was determined in Boletus edulis. The concentration of all heavy metals significantly differed (p < 0.001) between examined saprophytic and ectomycorrhizal mushrooms. Considering anatomical part of the fruiting body (cap-stipe), a considerably higher concentration of the analyzed elements was found in the cap for all mushroom species. According to calculated bioconcentration factors, all the examined species were found to be bioexclusors of Ni, Cr, and Pb and bioaccumulators of Cd and Hg. Cluster analysis performed on the basis of the accumulation of the studied metals revealed great phenotypic similarity of mushroom species belonging to the same genus and partial similarity of species of the same ecological affiliation.


Influence of induced water stress in ponderosa pine on pine sawflies.
Three levels of water stress were induced on pole-size ponderosa pine (Pinus ponderosa) to determine the influence of plant moisture stress on oviposition, survival, and growth of two species of pine sawfly (Neodiprion fulviceps and N. autumnalis). It was found that water stress affected oviposition and subsequent egg survival but not larval development or survival. Stress had a negative effect on early season oviposition (N. fulviceps) and a positive effect on late season oviposition (N. autumnalis). Egg hatch was different between species and years and among treatment levels. Larval development, feeding, and survival were not affected by water stress. Overall, the effect of stress was not sufficient to explain population outbreaks of sawflies. Several hypotheses are presented as possible explanations for the observed experimental results.


Roles of insulin and glucose in the regulation of plasma FFA in the duck. I. In the absence of pancreatic glucagon.
The present study was undertaken to determine how free fatty acid (FFA) release by adipose tissue can occur in the absence of pancreatic glucagon, the most potent lipolytic hormone in the duck. Two possible explanations have successively been investigated. Replacement therapy experiments showed that glucose uptake was implicated in the phenomenon; indeed, when pre-operative insulin and glucose levels were restored after total pancreatectomy, plasma FFA progressively fell to a level significantly lower than the pre-operative value. The same effect was observed when the ducks were kept in a continuous state of hyperglycaemia, whereas "normal" levels of insulin or glucose alone were shown to be ineffective. On the other hand a compensatory mechanism for the lack of glucagon, by other lipolytic agents [with the intestine or the anterior pituitary as possible sources] has been excluded by associating the removal of these two organs with pancreatectomy. These experiments suggest that the lack of pancreatic glucagon induced by total pancreatectomy is essentially masked by a failure in glucose uptake due to the operation.


All nod genes of Rhizobium meliloti are involved in alfalfa nodulation by exo mutants.
Nodulation of alfalfa by exoB mutants of Rhizobium meliloti occurred without root hair curling or infection thread formation. nod exoB double mutants had the same nodulation deficiency as single nod mutants. Therefore, all the known nod genes are involved in nodule induction by exoB mutants, which apparently occurs via intercellular invasion.


Electrosurgery principles: cutting current and cutaneous surgery--Part II.
The use of cutting current for electrosurgical excision is a valuable procedure for the cutaneous surgeon. Last month, the basic principles of cutting current were reviewed (J Dermatol Surg Oncol 14:29-31, 1988). This month, Part II will cover the technical aspects of cutting current administration.


Efficacy of dapagliflozin in the treatment of HFrEF with obstructive sleep apnea syndrome (DAHOS study): study protocol for a multicentric, prospective, randomized controlled clinical trial.
Heart failure with reduced ejection fraction (HFrEF) is associated with sleep dyspnea (SDB), which plays an adverse role in the pathophysiology of the condition. SDB management in HFrEF, however, remains controversial. HFrEF's medical management has recently made significant progress with the discovery of new therapeutic avenues, namely sodia-glucose cotransporter-2 (SGLT-2) inhibitors, and better treatment of co-morbidities. Dapagliflozin, one of the SGLT-2 inhibitors, is a good candidate for correcting SDB of HFrEF patients because their known mechanisms of action are likely to counteract the pathophysiology of SDB in HFrEF. The trial is a 3-month, multicentric, prospective, randomized controlled clinical study. Patients (i.e., adults with left ventricular ejection fraction ≤ 40%, Apnoea-Hypopnoea Index ≥ 15) will be randomized to receive optimized heart failure therapy plus a standard dose of dapagliflozin, while the control group will receive only optimized heart failure therapy. Patients will be evaluated before and after 3 months (nocturnal ventilatory polygraphy, echocardiography, laboratory testing, and quality-of-life and SDB questionnaires). The primary outcome is the change in the Apnoea-Hypopnoea Index, before and after 3 months of treatment. www.chictr.org.cn , ChiCTR2100049834. Registered 10 August 2021.


Reply to the 'Comment on "The promise of microfluidic artificial lungs"' by G. Wagner, A. Kaesler, U. Steinseifer, T. Schmitz-Rode and J. Arens, Lab Chip, 2016, 16.
This response explores and discusses the critiques of Wagner et al. in their "Comment on 'The promise of microfluidic artificial lungs' by Joseph A. Potkay, Lab Chip, 2014, 14, 4122-4138".


Characterization of a potent and specific class of antisense oligonucleotide inhibitor of human protein kinase C-alpha expression.
The use of antisense oligonucleotides to inhibit the expression of targeted mRNA sequences is becoming increasingly commonplace. Although effective, the most widely used oligonucleotide modification (phosphorothioate) has some limitations. In previous studies we have described a 20-mer phosphorothioate oligodeoxynucleotide inhibitor of human protein kinase C-alpha expression. In an effort to identify improved antisense inhibitors of protein kinase C expression, a series of 2' modifications have been incorporated into the protein kinase C-alpha targeting oligonucleotide, and the effects on oligonucleotide biophysical characteristics and pharmacology evaluated. The incorporation of 2'-O-(2-methoxy)ethyl chemistry resulted in a number of significant improvements in oligonucleotide characteristics. These include an increase in hybridization affinity toward a complementary RNA (1.5 degrees C per modification) and an increase in resistance toward both 3'-exonuclease and intracellular nucleases. These improvements result in a substantial increase in oligonucleotide potency (>20-fold after 72 h). The most active compound identified was used to examine the role played by protein kinase C-alpha in mediating the phorbol ester-induced changes in c-fos, c-jun, and junB expression in A549 lung epithelial cells. Depletion of protein kinase C-alpha protein expression by this oligonucleotide lead to a reduction in c-jun expression but not c-fos or junB. These results demonstrate that 2'-O-(2-methoxy)ethyl-modified antisense oligonucleotides are 1) effective inhibitors of protein kinase C-alpha expression, and 2) represent a class of antisense oligonucleotide which are much more effective inhibitors of gene expression than the widely used phosphorothioate antisense oligodeoxynucleotides.


[Hydatid cyst of the pancreas. Apropos of 2 case reports].
Hydatic cyst of pancreas is a rare disease, the symptomatology is polymorph and the diagnosis is rarely evocated before surgery. Epidemiological, clinical, biological (immunofluorescence) and echographic data should allow its better detection. Surgical treatment is function of the cyst localisation: exeresis for left lesions and conservative surgery for right lesions.


Cyclopentanedi- and tricarboxylic acids as squalene synthase inhibitors: syntheses and evaluation.
Based on earlier lead squalene synthase inhibitor A-87049 (3) and zaragozic acids, a series of cyclopentanedi- and tricarboxylic acids were synthesized and evaluated against the enzyme. Some exhibited good potency and SAR revealed the importance of conformation and substitution pattern of these synthetic inhibitors.


Absence of immunity to type II collagen and proteoglycan in osteoarthritic C57BL mice.
We measured immunity to type II collagen and proteoglycans in osteoarthritic C57BL mice to determine whether it is related to osteoarthritis pathogenesis. Histological examination revealed articular cartilage lesions in all mice and synovitis in only a few mice. Immunological responses to type II collagen were found in collagen arthritic mice, but not in C57BL mice. Furthermore, immunological responses to proteoglycans were observed in proteoglycan-immunized mice, but not in C57BL mice. Therefore, articular cartilage degeneration may not result in autoimmunity to type II collagen and proteoglycans in osteoarthritis of C57BL mice, and immune responses to these components may not be a primary etiology of osteoarthritis in this model.


Hyperhomocysteinemia in patients with pulmonary embolism is associated with impaired plasma fibrinolytic capacity.
Hyperhomocysteinemia (HHcy) affects haemostasis and shifts its balance in favour of thrombosis. In vitro and in vivo studies suggested that HHcy may impair fibrinolysis either by influencing the plasma levels of fibrinolytic factors or by altering the fibrinogen structure. We investigated the influence of mild HHcy levels on plasma fibrinolytic potential by using clot lysis time (CLT) and fibrin susceptibility to plasmin-induced lysis in 94 patients with previous pulmonary embolism and no pulmonary hypertension. CLT was measured as lysis time of tissue factor induced clots exposed to exogenous tissue plasminogen activator (t-PA). The rate of in vitro plasmin-mediated cleavage of fibrin β-chain was assessed over a 6-h period on fibrin clots, which were obtained by exposition to thrombin of purified fibrinogen. Homocysteine plasma levels were measured by Abbott Imx immunoassay and we considered as altered the values above 15 μmol/L according to the literature. In 68 patients homocysteine levels were below 15 μmol/L (NHcy) and in 26 they were above (HHcy). Significant differences were observed between the two groups regarding plasma fibrinolytic potential (p = 0.016), TAFIact (expressed as clot lysis ratio) (p = 0.02), t-PA (0.008) and PLG (0.037), but not for the other assessed components. The HHcy-patients had a threefold higher risk to have an impaired fibrinolysis. Instead, a multivariate logistic regression analysis adjusted for significances of univariate showed that HHcy (OR 5.2 95% CI 1.7-15.9; p = 0.003) and BMI (OR 5.0 95% CI 1.6-15.9; p = 0.006) resulted independently associated with impaired fibrinolytic activity. HHcy affects TAFI-mediated hypofibrinolysis but not fibrin(ogen) structure or function as documented by fibrin degradation analysis.


c-Abl-induced Olig2 phosphorylation regulates the proliferation of oligodendrocyte precursor cells.
Oligodendrocytes (OLs), the myelinating cells in the central nervous system (CNS), are differentiated from OL progenitor cells (OPCs). The proliferation of existing OPCs is indispensable for myelination during CNS development and remyelination in response to demyelination stimulation. The transcription factor Olig2 is required for the specification of OLs and is expressed in the OL lineage. However, the post-translational modification of Olig2 in the proliferation of OPCs is poorly understood. Herein, we identified that c-Abl directly phosphorylates Olig2 mainly at the Tyr137 site, and that Olig2 phosphorylation is essential for OPC proliferation. The expression levels of c-Abl gradually decreased with brain development; moreover, c-Abl was highly expressed in OPCs. OL-specific c-Abl knockout at the developmental stage led to an insufficient proliferation of OPCs, a decreased expression of myelin-related genes, and myelination retardation. Accordingly, a c-Abl-specific kinase inhibitor suppressed OPC proliferation in vitro. Furthermore, we observed that OL-specific c-Abl knockout reduced OPC proliferation and remyelination in a cuprizone model of demyelination. In addition, we found that nilotinib, a clinically used c-Abl inhibitor, decreased the expression of myelin basic protein (Mbp) and motor coordination in mice, indicating a neurological side effect of a long-term administration of the c-Abl inhibitor. Thus, we identified the important role of c-Abl in OLs during developmental myelination and remyelination in a disease model.


Gromerulocystic Kidney Disease in a Transplanted Kidney: Case Report.
The patient was a 28-year-old man with chronic kidney disease in stage 5 and in the course of chronic membranoroliferative glomerulonephritis. The patient was treated for a period of 2 months using peritoneal dialysis. In September 2014, he had a kidney transplant from a deceased donor. Four months after transplantation the patient was admitted to the hospital for a protocol biopsy. His creatinine was 1.5 mg/dL and urea was 59 mg/dL, urinalysis was normal in blood count with a normocytic anemia-hemoglobin level of 7.8 mmol/L. We obtained a histopathological evaluation of the cortex and medulla of the kidney. Glomeruli dilatation of Bowman space with reduced glomerular capillary tufts was found in the section. Histopathological evaluation indicated gromerulocystic kidney disease in a transplanted kidney.


Inter-professional clinical practice guideline for vocational evaluation following traumatic brain injury: a systematic and evidence-based approach.
This paper introduces an inter-professional clinical practice guideline for vocational evaluation following traumatic brain injury. This guideline aims to explicate the processes and factors relevant to vocational evaluation to assist evaluators (i.e. health care teams, individuals and employers) in collaboratively determining if clients are able to work and to make recommendations for work entry, re-entry or vocational planning. Methods in the Canadian Medical Association's (CMA) Handbook on Clinical Practice Guideline and the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument were utilized to ensure rigour. Steps in the CMA handbook were followed and included: (1) identifying the guideline's objective and questions; (2) systematic literature review; (3) study selection and quality appraisal; (4) development of clear recommendations by key stakeholders; (5) guideline pilot testing and endorsement. The resulting guideline includes 17 key recommendations within the seven domains: (1) evaluation purpose and rationale; (2) initial intake process; (3) assessment of the personal domain; (4) assessment of the environment; (5) assessment of occupational/job requirements; (6) analysis and synthesis; (7) evaluation recommendations. The guideline may be useful to individually practicing clinicians, health care teams, employers and individuals with TBI. Future research will formally examine the success of the guideline's implementation.


Large-scale snake genome analyses provide insights into vertebrate development.
Snakes are a remarkable squamate lineage with unique morphological adaptations, especially those related to the evolution of vertebrate skeletons, organs, and sensory systems. To clarify the genetic underpinnings of snake phenotypes, we assembled and analyzed 14 de novo genomes from 12 snake families. We also investigated the genetic basis of the morphological characteristics of snakes using functional experiments. We identified genes, regulatory elements, and structural variations that have potentially contributed to the evolution of limb loss, an elongated body plan, asymmetrical lungs, sensory systems, and digestive adaptations in snakes. We identified some of the genes and regulatory elements that might have shaped the evolution of vision, the skeletal system and diet in blind snakes, and thermoreception in infrared-sensitive snakes. Our study provides insights into the evolution and development of snakes and vertebrates.


Long-term microclimatic stress causes rapid adaptive radiation of kaiABC clock gene family in a cyanobacterium, Nostoc linckia, from "Evolution Canyons" I and II, Israel.
Cyanobacteria are the only prokaryotes known thus far possessing regulation of physiological functions with approximate daily periodicity, or circadian rhythms, that are controlled by a cluster of three genes, kaiA, kaiB, and kaiC. Here we demonstrate considerably higher genetic polymorphism and extremely rapid evolution of the kaiABC gene family in a filamentous cyanobacterium, Nostoc linckia, permanently exposed to the acute natural environmental stress in the two microsite evolutionary models known as "Evolution Canyons," I (Mount Carmel) and II (Upper Galilee) in Israel. The family consists of five distinct subfamilies (kaiI-kaiV) comprising at least 20 functional genes and pseudogenes. The obtained data suggest that the duplications of kai genes have adaptive significance, and some of them are evolutionarily quite recent (approximately 80,000 years ago). The observed patterns of within- and between-subfamily polymorphisms indicate that positive diversifying, balancing, and purifying selections are the principal driving forces of the kai gene family's evolution.


Diversity of staminal nectariferous appendages in disymmetric and zygomorphic flowers of Fumarioideae (Papaveraceae).
Staminal nectaries show diversity in their position, size, shape, color, and number in Ranunculales. In Papaveraceae, nectaries only appear at the base of stamen in these lineages with disymmetric and zygomorphic flowers. However, the diversity of the staminal nectaries' developmental characteristics and structure is unknown. The diversity of staminal nectaries of Hypecoum erectum, Ichtyoselmis macrantha, Adlumia asiatica, Dactylicapnos torulosa, Corydalis edulis, and Fumaria officinalis (six species belonging to six genera, respectively) in the Fumarioideae was investigated under scanning electron microscopy, light microscopy, and transmission electron microscopy. In all species studied, according to the developmental characteristics of the nectaries, four developmental stages can be divided into initiation, enlargement, differentiation, and maturation, and the number of nectaries can be determined at the stage of initiation (stage 1), and morphological differentiation occurs at the developmental stage 3. The staminal nectaries consist of secretory epidermis, parenchyma tissue, and phloem with some sieve tube elements reaching the secretory parenchyma cells; however, the number of cell layers of parenchyma can vary from 30 to 40 in I. macrantha and D. torulosa, to only 5 to 10 like in F. officinalis. Secretory epidermis cells are larger than secretory parenchyma cells with abundant microchannels on the outer cell wall. There were abundant mitochondria, Golgi bodies, rough endoplasmic reticulum, and plastids in secretory parenchyma cells. Nectar is stored in the intercellular space and exuded to the exterior via microchannels. In A. asiatica, according to the evidence of small secretory cell characteristics such as dense cytoplasm, and numerous mitochondria, together with the filamentous secretions present on the surface of epidermal cells on groove, it can be inferred that the U-shaped sulcate which is located in the white projection formed at the filament of triplets in A. asiatica is nectariferous.


Reconstitution of H-2 class I expression by gene transfection decreases susceptibility to natural killer cells of an EL4 class I loss variant.
Several reports have suggested that an inverse correlation exists between major histocompatibility complex class I expression and the susceptibility to natural killer (NK)-mediated lysis. For example, the increased class I expression induced by interferon-gamma was always accompanied by an increased resistance to NK lysis. Likewise, class I loss variants were often more NK susceptible than their normal counterparts. To investigate whether the inverse correlation between class I expression and NK susceptibility was fortuitous or whether the class I molecules were directly responsible for this effect we resorted to gene transfection studies. From the murine thymoma line EL4 and H-2Db- and Kb-negative variant S3 was selected. This variant was highly susceptible to NK lysis. S3 was found to have a defect in beta 2-microglobulin gene expression. Therefore, restoration of Db and Kb expression could be achieved by transfection with the beta 2-microglobulin gene. This resulted in a strong decrease in susceptibility to NK lysis to the level of the H-2+ parental EL4. Transfection with class II genes had no effect. Blocking of the class I molecules on the H-2+ cells with anti-H-2b F(ab')2 fragments increased the susceptibility to NK cells to the level of the H-2- variant S3. These data demonstrate that the class I molecules on the targets are directly responsible for regulation of NK susceptibility but the mechanism is not clear. Possibly the class I molecules interfere with the unknown NK target structures.


Role of the fourth complement component (C4) in the regulation of contact sensitivity. II. Qualitative differences between C4 molecules from high- and low-C4 mouse strains.
Lymph node cells collected from CBA/J mice 4 days after painting with picryl chloride induce contact sensitivity in naive recipient mice by virtue of hapten IgM immuno complexes. The immunizing capacity of these cells ("4-day" cells) is abolished after incubation of the cells with a C4-deficient guinea pig serum reconstituted with plasma or purified C4 from mice with high C4 levels (C4h), but not with plasma or purified C4 from mice with low C4 levels (C41). The inhibition of the immunizing capacity of 4-day cells is due to the activation of the early components of the classical complement pathway which is likely to result in the solubilization of membrane-bound immunocomplexes. However, the same amounts of CBA/J and BALB/c C4 have a different effect in inhibiting the induction of contact sensitivity by 4-day cells. In fact, by dose-response experiments, we have found that the amount of C41 able to inhibit the induction of contact sensitivity is about threefold higher than that of C4h. Analysis of the covalent binding ability of C4h and C41 reveals that C4h is able to bind to the surface of 4-day cells more efficiently than C41 and this probably accounts for the difference of the two C4 molecules in inhibiting the immunizing capacity of 4-day cells. Results are discussed in terms of different reactivities of C4h and C41 with the surface of 4-day cells.


Effect of a capsular tension ring on intraocular lens decentration and tilting after cataract surgery.
To evaluate the effect of a capsular tension ring (CTR) on the tilting and decentration of intraocular lenses (IOLs) after cataract surgery. Department of Ophthalmology, Ilsan Paik Hospital, Inje University, Kyunggyi-do, Korea. Cataract surgery was performed in both eyes of 20 patients ranging in age from 57 to 75 years. The 40 eyes were divided into 2 groups based on whether a CTR (Lucid Korea) was implanted. Each patient received a CTR in 1 eye only. All IOLs (AcrySof MA60BM, Alcon) were implanted in the capsular bag after a continuous curvilinear capsulorhexis smaller than the IOL optic was created and phacoemulsification performed. The extent of IOL tilting and decentration was measured with the EAS-1000 anterior eye segment analysis system 7, 30, and 60 days after surgery. The extent of IOL decentration was statistically significantly less in eyes with both an IOL and CTR than in those with an IOL only. The mean decentration in the CTR-IOL group was 0.38 mm +/- 0.16 (SD) at 7 days, 0.43 +/- 0.15 mm at 30 days, and 0.42 +/- 0.17 mm at 60 days. The mean values in the IOL-only group were 0.49 +/- 0.11 mm, 0.53 +/- 0.14 mm, and 0.57 +/- 0.16 mm, respectively. The amount of IOL tilting was also significantly less in the CTR-IOL group. The mean tilting in the CTR-IOL group was 2.22 +/- 0.46 degrees at 7 days, 2.36 +/- 0.50 degrees at 30 days, and 2.47 +/- 0.40 degrees at 60 days. The mean values in the IOL-only group were 3.14 +/- 0.65 degrees, 2.91 +/- 0.67 degrees, and 3.06 +/- 0.56 degrees, respectively. These results indicate that the CTR reduces undesirable postsurgical IOL movement for at least 60 days.


CAP2 in cardiac conduction, sudden cardiac death and eye development.
Sudden cardiac death kills 180,000 to 450,000 Americans annually, predominantly males. A locus that confers a risk for sudden cardiac death, cardiac conduction disease, and a newly described developmental disorder (6p22 syndrome) is located at 6p22. One gene at 6p22 is CAP2, which encodes a cytoskeletal protein that regulates actin dynamics. To determine the role of CAP2 in vivo, we generated knockout (KO) mice. cap2(-)/cap2(-) males were underrepresented at weaning and ~70% died by 12 weeks of age, but cap2(-)/cap2(-) females survived at close to the expected levels and lived normal life spans. CAP2 knockouts resembled patients with 6p22 syndrome in that mice were smaller and they developed microphthalmia and cardiac disease. The cardiac disease included cardiac conduction disease (CCD) and, after six months of age, dilated cardiomyopathy (DCM), most noticeably in the males. To address the mechanisms underlying these phenotypes, we used Cre-mediated recombination to knock out CAP2 in cardiomyocytes. We found that the mice developed CCD, leading to sudden cardiac death from complete heart block, but no longer developed DCM or the other phenotypes, including sex bias. These studies establish a direct role for CAP2 and actin dynamics in sudden cardiac death and cardiac conduction disease.


Attenuation mechanism of virulent infectious bronchitis virus strain with QX genotype by continuous passage in chicken embryos.
The virulent isolate SDZB0808 of QX-type infectious bronchitis virus (IBV) was continuously passaged in chicken embryos for 110 generations. The safety and immune efficacy of the 110th generation of IBVs (P110) were evaluated. Damage was not found in the appearance of the 3-day-old specific-pathogen-free (SPF) chicks immunized with 10(4.5) EID50 (median embryo infective dose) of P110 by intranasal and ocular administration. At 14 d after the vaccination with 10(4.5) EID50 of P110, all the 3-day-old SPF chicks were immune from the attack of the homologous virulent strain SDZB0808 and the heterologous virulent strain SDIB821/2012. The whole genome sequencing of SDZB0808 of different generations (P1-P110) indicated that the replicase 1a sequences of P60-P110 all lost a length of 30bp in the same region. Specific primers were designed according to the differences in the genomes of P1-P110. SYBR Green I real-time quantitative PCR was adopted to analyze the proportion of the viruses with 30bp deletion in P60, P100, and P110. Results showed that with the passage in chicken embryos, the proportion of the viruses with 30bp deletion gradually increased. Almost 100% of the viruses in the P110 had 30bp deletion in the replicase 1a sequence. Therefore, the attenuation of IBV's virulence may be the outcome of directional screening in the chicken embryos. This work confirmed the high safety and immune efficacy of P110 in SPF chickens. Thus, P110 can serve as an attenuated IBV vaccine candidate.


Occurrence, seasonal variations, and eco-risk of currently using organochlorine pesticides in surface seawater of the East China Sea and Western Pacific Ocean.
We studied 19 targets currently using organochlorine pesticides (CUOCPs) from 98 samples in the Western Pacific Ocean and the East China Sea collected in 2019, 2020, and 2021. The samples were analyzed using a novel High-throat/High-volume Solid-Phase Extraction method. Eighteen individual CUOCPs were above the method detection limits. The levels of ∑19CUOCPs ranged from 0.13 to 17.80 ng/L, with an average of 3.13 ± 14.67 ng/L. Dicofol was the main pollutant in the Western Pacific Ocean, while Pyridaben dominated the East China Sea. In the summer, land-source input was the primary source in the Western Pacific Ocean and the East China Sea. Historical residues were the main source in the East China Sea in spring. In the summer, the ecological risk assessment results indicated a relatively low risk to the Western Pacific Ocean and the East China Sea.


Carbon monoxide-saturated preservation solution protects lung grafts from ischemia-reperfusion injury.
In previous work we have demonstrated that delivery of low concentrations (250 ppm) of carbon monoxide by means of inhalation to donors, recipients, or both protects transplanted lungs from ischemia-reperfusion injury (improved gas exchange, diminished intragraft and systemic inflammation, and retention of graft vascular endothelial cell ultrastructure). In this study we examined whether delivery of carbon monoxide to lung grafts in the preservation solution could protect against lung ischemia-reperfusion injury. Orthotopic left lung transplantation was performed in syngeneic Lewis to Lewis rats. Grafts were preserved in University of Wisconsin solution with or without (control solution) carbon monoxide at 4 degrees C for 6 hours. Carbon monoxide gas (5% or 100%) was bubbled into University of Wisconsin solution at 4 degrees C for 5 minutes before use. In control animals, ischemia-reperfusion injury resulted in significant deterioration of graft function and was associated with a massive cellular infiltrate 2 hours after reperfusion. Grafts stored in University of Wisconsin solution with carbon monoxide (5%), however, demonstrated significantly better gas exchange and significantly reduced intragraft inflammation (reduced inflammatory mediators and cellular infiltrate). Experiments demonstrated that the protective effects afforded by 100% University of Wisconsin solution with carbon monoxide were not as potent as those of 5% University of Wisconsin solution with carbon monoxide. This study demonstrates that 5% carbon monoxide as an additive to the cold flush/preservation solution can impart potent anti-inflammatory and cytoprotective effects after cold preservation and transplantation of lung grafts. Such ex vivo treatment of lung grafts with carbon monoxide can minimize concerns associated with carbon monoxide inhalation and might offer the opportunity to significantly advance the application of carbon monoxide in the clinical setting.


Multi-layer topological transmissions of spoof surface plasmon polaritons.
Spoof surface plasmon polaritons (SPPs) in microwave frequency provide a high field confinement in subwavelength scale and low-loss and flexible transmissions, which have been widely used in novel transmission waveguides and functional devices. To play more important roles in modern integrated circuits and systems, it is necessary and helpful for the SPP modes to propagate among different layers of devices and chips. Owing to the highly confined property and organized near-field distribution, we show that the spoof SPPs could be easily transmitted from one layer into another layer via metallic holes and arc-shaped transitions. Such designs are suitable for both the ultrathin and flexible single-strip SPP waveguide and double-strip SPP waveguide for active SPP devices. Numerical simulations and experimental results demonstrate the broadband and high-efficiency multi-layer topological transmissions with controllable absorption that is related to the superposition area of corrugated metallic strips. The transmission coefficient of single-strip SPP waveguide is no worse than -0.8 dB within frequency band from 2.67 GHz to 10.2 GHz while the transmission of double-strip SPP waveguide keeps above -1 dB within frequency band from 2.26 GHz to 11.8 GHz. The proposed method will enhance the realizations of highly complicated plasmonic integrated circuits.


Tracheal diverticula in infants: a report of three cases.
Tracheal diverticulum is a paratracheal air cyst in connection with the trachea. It may be congenital or acquired. Congenital tracheal diverticula in infants are rare. Imaging techniques such as high-resolution computed tomography and three-dimensional reconstruction of the airway are useful for diagnosis. Here we report three cases with congenital tracheal diverticula, which were diagnosed by imaging techniques.


Novel guar gum/Al2O3 nanocomposite as an effective photocatalyst for the degradation of malachite green dye.
Guar gum/Al2O3 (GG/AO) nanocomposite was prepared using simple and cost effective sol-gel method. This nanocomposite was characterized by several analytical techniques viz. scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), thermal analysis (TGA/DTA), Fourier transform infrared spectroscopy (FTIR) and ultraviolet-visible spectroscopy (UV-vis). The FTIR analysis confirmed that GG/AO composite material was formed. TEM images inferred the particle size in the range between 20 and 45nm. GG/AO nanocomposite exhibited good photocatalytic performance for malachite green (MG) dye (dye initial concentration 1.5×10(-5)M) degradation from aqueous phase. The adsorption followed by photocatalysis and coupled adsorption/photocatalysis reaction achieved about 80% and 90% degradation of MG dye under solar irradiation. Antibacterial test showed the excellent activity of GG/AO nanocomposite against Staphylococcus aureus.


Demography, heritability and genetic correlation of feline hip dysplasia and response to selection in a health screening programme.
Feline hip dysplasia (FHD) is a debilitating condition affecting the hip joints of millions of domestic cats worldwide. Despite this, little is known about FHD except that it is relatively common in the large breed Maine Coon. We used 20 years of data from 5038 pedigree-registered Maine Coon cats in a radiographic health screening programme for FHD to determine, for the first time, its heritability, genetic correlation to body mass and response to selection. FHD prevalence was 37.4%, with no sex predilection; however, FHD severity increased with age and body mass. Heritability of the radiographic categories used to classify FHD severity was 0.36 (95%CI: 0.30-0.43). The severity of FHD symptoms was also genetically correlated with body mass (0.285), suggesting that selection for a large body type in this breed concurrently selects for FHD. Support for this was found by following generational responses to selective breeding against FHD. Not only did selective breeding successfully reduce the severity of FHD symptoms in descendants, but these cats were also smaller than their ancestors (-33g per generation). This study highlights the value of breeding programmes against FHD and cautions against breed standards that actively encourage large bodied cats.


Differential phase register of Hes1 oscillations with mitoses underlies cell-cycle heterogeneity in ER+ breast cancer cells.
Here, we study the dynamical expression of endogenously labeled Hes1, a transcriptional repressor implicated in controlling cell proliferation, to understand how cell-cycle length heterogeneity is generated in estrogen receptor (ER)+ breast cancer cells. We find that Hes1 shows oscillatory expression with ∼25 h periodicity and during each cell cycle has a variable peak in G1, a trough around G1-S transition, and a less variable second peak in G2/M. Compared to other subpopulations, the cell cycle in CD44HighCD24Low cancer stem cells is longest and most variable. Most cells divide around the peak of the Hes1 expression wave, but preceding mitoses in slow dividing CD44HighCD24Low cells appear phase-shifted, resulting in a late-onset Hes1 peak in G1. The position, duration, and shape of this peak, rather than the Hes1 expression levels, are good predictors of cell-cycle length. Diminishing Hes1 oscillations by enforcing sustained expression slows down the cell cycle, impairs proliferation, abolishes the dynamic expression of p21, and increases the percentage of CD44HighCD24Low cells. Reciprocally, blocking the cell cycle causes an elongation of Hes1 periodicity, suggesting a bidirectional interaction of the Hes1 oscillator and the cell cycle. We propose that Hes1 oscillations are functionally important for the efficient progression of the cell cycle and that the position of mitosis in relation to the Hes1 wave underlies cell-cycle length heterogeneity in cancer cell subpopulations.


The anorectic effect of satietin is unrelated to carbohydrate metabolism.
The effect of satietin and amphetamine on the carbohydrate metabolism of free fed and food deprived rats was studied. Rats deprived of food for 96 hours maintained normal glucose and glucagon blood levels but the blood concentration of insulin dropped from 232.02 +/- 23.93 to 12.48 +/- 0.71 pmol/l. Amphetamine (500 micrograms/animal, intracerebroventricularly) left in normally fed rats the blood concentration of glucose, insulin and glucagon unchanged. The same treatment, however, increased the insulin concentration in the blood of food deprived rats from 11.37 +/- 4.43 to 73.47 +/- 8.29 pmol/l. Glucose and glucagon, as well as insulin levels remained unchanged in both normally fed and food deprived rats when treated with satietin (20 micrograms/rat, intracerebroventricularly). It was concluded that the anorectic effect of satietin is unrelated to carbohydrate metabolism.


Peritoneal fluid cytokines and sICAM-1 in minimal endometriosis: search for discriminating factors between infertility and/or endometriosis.
To evaluate cytokine levels (IL-1beta, TNF-alpha, IL-6, IL-8), soluble intercellular adhesion molecule-1 (sICAM-1) and number of macrophages in peritoneal fluid (PF) of women with no minimal endometriosis and associated (or not) infertility in order to discriminate between infertility and/or endometriosis. Cytokines and sICAM-1 were measured by using quantitative enzyme-linked immunosorbent assay (ELISA) while the macrophages were identified by May-Grunwald-Giemsa and non-specific esterase staining and presented as medians. The measurements were performed in 78 women belonging to four selected subgroups according to their endometriosis and/or infertility status. Statistical analysis was performed using Kruskal-Wallis non-parametric ANOVA test. Additionally, discriminant function analyses were performed. We have found the most elevated macrophage numbers in the groups of women with endometriosis. IL-1beta did not present any statistically significant values differentiating the analysed subgroups. IL-6 (110.0 pg/ml) and TNF-alpha exhibited the highest concentrations (statistically significant) in a group of fertile women with endometriosis. IL-8 clearly differentiated between the subgroups with infertility and sICAM-1 was statistically significantly elevated in the subgroups of infertile women. In the forward discriminant analysis, when subdividing the studied population according to its infertility status (we considered macrophages, IL-8 and IL-6 in order of probability values), we have found striking probability value of 92% for the correct classification into an infertile population. Out of the range of the analysed factors we have found only the sICAM-1 to be singled out between the standard discriminant analysis and the forward one. However, this important flagging molecule might be of considerable value for discrimination between different types of pathology at the level of immune effector function. The increased levels of TNF-alpha and IL-6 signified a group of fertile women with endometriosis; however only IL-6 presented a discriminating value in multifunctional analysis of examined subgroups. The analysed range of factors had a greater tendency to discriminate between infertility status rather than endometriosis.


Evidence for abnormal platelet glycoprotein expression in diabetes mellitus.
In 41 diabetics (27 type I, 14 type II) and in 23 healthy controls the number of glycoprotein (GP) GPIB and GPIIB/IIIA molecules were determined on resting, peripheral platelets by means of flowcytometry after immunostaining with monoclonal antibodies which bind independently from the state of activation. The average number of both glycoproteins per platelet was significantly elevated (GPIB: 54,100 x 1.27 +/- 1 vs. 39,100 x 1.3 +/- 1 GPIIB/IIIA: 77,500 x 1.3 +/- 1 vs. 62,700 x 1.3 +/- 1, in diabetic patients. Platelet volume was significantly correlated with the number of GPIB molecules on normal and diabetic platelets (r (normal) = 0.52 +/- 0.07; r (diabetic) = 0.46 +/- 0.1). Additionally, von Willebrand factor-related antigen (vWF: AG) was increased to 129% x 1.3 +/- 1 in diabetics vs. 111% x 1.4 in controls. The increase of vWF: AG was significantly correlated with HbA1 (r = 0.38*) and seemed to depend on chronic hyperglycaemia. Since platelet glycoprotein receptor status is regulated by the bone-marrow megakaryocyto- thrombopoiesis, our observations support the hypothesis that platelet hyperactivity in the diabetic state may be due to primarily altered production of platelets with an increased number of functional glycoproteins. This may be paralleled by increased plasma levels of cytoadhesive proteins like vWF: AG, which interact with the studied glycoproteins and thereby potentiate the risk of disturbed microhaemorrheology.


The central inflammasome adaptor protein ASC activates the inflammasome after transition from a soluble to an insoluble state.
Apoptosis-associated speck-like protein containing a caspase recruitment domain (CARD) (ASC) is a 22 kDa protein that functions as the central adaptor for inflammasome assembly. ASC forms insoluble specks in monocytes undergoing pyroptosis, and the polymerization of ASC provides a template of CARDs that leads to proximity-mediated autoactivation of caspase-1 in canonical inflammasomes. However, specks are insoluble protein complexes, and solubility is typically important for protein function. Therefore, we sought to define whether ASC specks comprise active inflammasome complexes or are simply the end stage of exhausted ASC polymers. Using a THP-1 cell-lysing model of caspase-1 activation that is ASC dependent, we compared caspase-1 activation induced by preassembled insoluble ASC specks and soluble monomeric forms of ASC. Unexpectedly, after controlling for the concentration dependence of ASC oligomerization, we found that only insoluble forms of ASC promoted caspase-1 autocatalysis. This link to insolubility was recapitulated with recombinant ASC. We show that purified recombinant ASC spontaneously precipitated and was functional, whereas the maltose-binding protein-ASC fusion to ASC (promoting enhanced solubility) was inactive until induced to insolubility by binding to amylose beads. This functional link to insolubility also held true for the Y146A mutation of the CARD of ASC, which avoids insolubility and caspase-1 activation. Thus, we conclude that the role of ASC insolubility in inflammasome function is inextricably linked to its pyrin domain-mediated and CARD-mediated polymerizations. These findings will support future studies into the molecular mechanisms controlling ASC solubility.


A survey of the use of teicoplanin in patients with haematological malignancies and solid tumours.
A significant number of open and comparative studies have now addressed the use of teicoplanin in the treatment of documented or presumed infection in patients with haematological and non-haematological malignancy. Available evidence suggests that teicoplanin is an effective agent against such infections, with an excellent safety profile. The use of teicoplanin and vancomycin may be justified as part of the initial management of clinically infected right atrial catheters in patients with malignancy. The first-line use of glycopeptides may also be appropriate in units where streptococcal and methicillin resistant staphylococcal infections are prevalent. However, such a policy should be reviewed regularly. Except in the above situations, a delay in the introduction of either teicoplanin or vancomycin in cancer patients does not appear to produce any excess mortality, but there may be some additional morbidity in terms of fever and malaise. The introduction of glycopeptides as second-line agents is indicated for sensitive, microbiologically documented infections and for patients who have not responded to empirical, first-line therapy. Non-inpatient treatment with teicoplanin is an area of ongoing interest and may be justified on both humanitarian and pharmacoeconomic grounds. The use of glycopeptides in the prophylactic setting remains controversial and should be avoided while the emergence of resistance, particularly in enterococci, should be monitored closely.


Growth retardation versus overgrowth: Silver-Russell syndrome is genetically opposite to Beckwith-Wiedemann syndrome.
Human growth is a complex process that requires the appropriate interaction of many players. Central members in the growth pathways are regulated epigenetically and thereby reflect the profound significance of imprinting for correct mammalian ontogenesis. In this review, we show that the growth retardation disorder Silver-Russell syndrome (SRS) is a suitable model to decipher the role of imprinting in growth. As we will show, SRS should not only be regarded as the genetically (and clinically) opposite disease to Beckwith-Wiedemann syndrome, but it also represents the first human disorder with imprinting disturbances that affect two different chromosomes (i.e. chromosomes 7 and 11). Thus, a functional interaction between factors encoded by chromosomes 7 and 11 is likely.


Behavioural effects of the nicotinic agonists N-(3-pyridylmethyl)pyrrolidine and isoarecolone in rats.
The nicotinic agonists N-(3-pyridylmethyl)pyrrolidine (PMP) and isoarecolone have been compared with (-)-nicotine in three behavioural procedures and as inhibitors of [3H]-(-)-nicotine binding. Locomotor activity was recorded as movements between beams of infra-red light (ambulation). In experimentally naive rats, nicotine, PMP and isoarecolone reduced ambulation. In rats receiving nicotine chronically and previously exposed to the activity cages, nicotine and PMP increased ambulation in a dose-related manner. However, isoarecolone did not increase ambulation at doses that were active in other procedures. In rats trained to discriminate nicotine from saline in a two-bar operant conditioning procedure with food reinforcement, there was full generalization to PMP. It was also found that PMP potently inhibited the binding of [3H]-(-)-nicotine to rat brain membranes in vitro. These results were discussed with previous data for the discriminative stimulus and ligand-binding effects of isoarecolone obtained under similar conditions. The relative potency of PMP in different behavioural procedures was similar to that of (-)-nicotine. However, isoarecolone was relatively 10 times more potent in decreasing ambulation than would have been expected from its potency in the ligand-binding and discriminative stimulus procedures. The results suggest that the pharmacodynamic action of isoarecolone differs from that of nicotine and PMP, and that it will be a useful probe in further analyses of central nicotinic mechanisms.


Anesthesia for the pregnant HIV patient.
Numbers of HIV-infected individuals across the globe are increasing, as is the proportion of women infected with HIV. However, better understanding of the HIV virus, and rapidly evolving treatments has provided hope for millions of people world-wide. In the pregnant population, recent understanding of factors influencing vertical transmission has enabled dramatic reductions in mother-to-child transmission. The anesthesiologist is likely to encounter HIV-infected parturients in the delivery suite as part of routine practice, and should be aware of the current trends in obstetric -- as well as anesthetic -- best practice and management.


Pain after total hip arthroplasty: a psychiatric point of view.
After total hip arthroplasty (THA), many studies report that a small percentage of patients mention painful symptoms, whose origin remains more or less obscure. We investigated 1,000 patients who had undergone a THA at least one year before their inclusion in the survey protocol. Among these 1,000 patients, 64 were complaining of pain in the region of the operated hip. These were later examined and investigated, both clinically (physical and psychiatric examination) and paraclinically (radiography, biology). Those requiring it received adequate treatment and the others were only regularly followed up. We identified the cause of all but one patient's pain. In all cases except one, the symptoms of pain without physical cause had a psychiatric origin. The results of our study show that, if the clinical picture is not perfectly clear, a psychiatric screening before surgery could contribute to decreasing the incidence of pain syndrome after THA.


Factors contributing to COPD hospitalisations from 2010 to 2015: Variation among rural and metropolitan Australians.
Rural and remote populations experience the greatest burden of chronic obstructive pulmonary disease (COPD), the fifth leading cause of death in Australia. Currently there is a need to prioritise health services to improve health outcomes among those at higher risk of COPD. To investigate the differences in COPD hospitalisation between rural and urban populations and determine predictive factors contributing to COPD hospitalisation. Statewide hospitalisation data from 2010 to 2015 were obtained through the Victorian Admitted Episodes Dataset and other key data sets. The rates of hospitalisation were analysed using hierarchical multiple regression to examine the association between COPD hospitalisations and a number of predictor variables. The highest COPD incidence occurred in metropolitan males aged 85 years of age and older (35.092 hospitalisations per 1000 population). Among metropolitan residents, smoking, population density and household income had a significant association with COPD hospitalisations for both sexes. Among rural males, smoking rates, household income and rural land use (farming) were significant predictors of COPD hospitalisations. There was an overall stability in statewide COPD hospitalisation over the 5 years to 2015, P = 0.420. This investigation highlights many rural and regional areas have much lower COPD hospitalisation rates than metropolitan areas. Between males and females, there are heterogenetic factors that contribute to the significant variation associated with COPD hospitalisation in metropolitan and rural areas, such as rural land use among rural males. This indicates that risk factor assessments, beyond smoking alone, need to be individualised and prioritised in practice to optimise care.


The fetal serum alpha-fetoprotein and its relationship to immunoglobulins and birth weight at term.
The distribution of values of alpha-fetoprotein (AFP) was analyzed in the cord blood of 350 newborns divided into groups according to whether their mothers were normal, preeclamptic, or smokers. In addition, fetal birth weight and fetal IgA and IgM at term were correlated with AFP. Cord serum AFP values showed a unimodal bell-shaped distribution in 269 normal newborns with a mean of 22.7 +/- 11.3 (SD) micrograms/ml. The cord sera of infants of preeclamptic mothers and of smoking mothers showed a similar mean and distribution. As previously observed, AFP was correlated inversely with birth weight. No correlation existed between AFP and fetal Ig levels.


Surveillance study for clinical stage I testicular seminomas and nonseminomatous germ cell tumors.
Optimal therapy for stage I testicular tumors is still controversial. This study evaluated the efficacy of a surveillance policy for patients with testicular stage I seminomas and nonseminomatous germ cell tumors (NSGCT). From 1984 to 1996, 24 patients with stage I seminoma and 20 with stage INSGCT were followed after radical orchiectomy with tumor markers and imaging studies. All patients were followed for at least 2 years except for those who recurred within 2 years. Recurrent patients were treated with cisplatin-based chemotherapy. The median follow-up periods for seminoma and NSGCT patients were 41 and 54 months, respectively. Recurrences were detected in 2 seminoma (8.3%) and 10 NSGCT (50%) patients. Eleven of the 12 recurrent patients (92%) were detected within 2 years after orchiectomy. The seminoma patients both recurred in the retroperitoneal lymph nodes, while 70% of the NSGCT patients recurred in the lung and/or retroperitoneal lymph nodes. The recurrent seminoma patients were treated with chemotherapy and are alive without disease for 1 7 and 24 months afterorchiectomy. One NSGCT patient died of cancer, but the other 9 recurrent NSGCT patients are alive without disease at 25 to 113 months after orchiectomy. Surveillance alone is reliable for monitoring patients with stage I testicular seminoma and NSGCT. The majority of recurrences occurred within 2 years, necessitating intensive follow-up for 3 years. As the lung metastatic rates in NSGCT patients were high, a more accurate assessment for lung metastasis is desirable in these patients.


Inhibition of endogenous carcinoembryonic antigen (CEA) increases the apoptotic rate of colon cancer cells and inhibits metastatic tumor growth.
It has been suggested that carcinoembryonic antigen (CEA) enhances metastatic seeding of colon cancer cells due to its homo- and heterophilic binding properties. Our recent finding that endogenous CEA protects colon cancer cells against apoptosis suggests a more complex role of CEA in cancer progression. In this study we compared the in vitro effects of endogenous CEA on tumor cell aggregation and cell cycle regulation of human HT29 colon cancer cells with the corresponding in vivo effects, i.e. tumor cell seeding and formation of metastatic lesions. Stable expression of CEA targeted ribozymes (Rz) under control of a tet-off promoter system allowed regulation of CEA levels on the mRNA and protein level by 50%. Downregulation of CEA levels inhibited tumor cell aggregation by 70%. In accordance with previous studies, reduction of CEA levels increased in vitro the apoptotic rate and reduced colony formation by 30% to 50%. To determine the in vivo effect of CEA-dependent aggregate formation and its growth regulating role under apoptotic stress, HT29 cells with high and low CEA levels, respectively, were injected into nude mice. Immunostaining of lung microsections revealed similar numbers of tumor cells one hour after injection. 24 h later virtually all cells were removed from the lung in both groups. However, after 6 weeks all doxycycline treated mice (Rz off = CEA high) showed 14.5 +/- 4.6 metastatic lung lesions/mouse while 0.2 +/- 0.2 lesions/mouse appeared in the untreated group (Rz on = CEA low) (P < 0.001). Our study demonstrates a multifunctional role of CEA and indicates a prometastatic role of CEA independent of its adhesive function possibly due to its anti-apoptotic function.


Endovascular management of massive post-partum haemorrhage in abnormal placental implantation deliveries.
To retrospectively evaluate safety and efficacy of pelvic artery embolisation (PAE) in post-partum haemorrhage (PPH) in abnormal placental implantation (API) deliveries. From January 2009 to November 2013, 12 patients with API and intractable intraoperative PPH underwent PAE after caesarean delivery to control a haemorrhage (in four of these cases after hysterectomy). Arterial access was obtained prior to the delivery; PAE was performed in the obstetrics operating room by an interventional radiologist that was present with an interventional radiology (IR) team during the delivery. PAE was successful in preventing bleeding and avoid hysterectomy in four cases (group A). Uterine atony and disseminated intravascular coagulation caused failure of PAE requiring hysterectomy in four patients (group B). PAE prevented bleeding post-hysterectomy in the remaining four cases (group C). Technical success (cessation of contrast extravasation on angiography or occlusion of the selected artery) was 100 %. Maternal and foetal mortality and morbidity were 0 %. PAE is a minimal invasive technique that may help to prevent hysterectomy and control PPH in API pregnancies without complications. Embolisation should be performed on an emergency basis. For such cases, an IR team on standby in the obstetrics theatre may be useful to prevent hysterectomy, blood loss and limit morbidity. • Endovascular treatment is a validated technique in post-partum haemorrhage. • Abnormal placental implantation is a risk factor for post-partum haemorrhage. • We propose an interventional radiologist standby in the delivery room.


Remembering Navasard V. Karapetyan (1936-2015).
Navasard Vaganovich Karapetyan (September 6, 1936-March 6, 2015) began his scientific career at the Bach Institute of Biochemistry of the Russian Academy of Sciences, Moscow, and was associated with this institute for over 56 years. He worked in the area of biochemistry and biophysics of photosynthesis and was especially known for his studies on chlorophyll a fluorescence in higher plants and cyanobacteria, molecular organization of Photosystem I, photoprotective energy dissipation, and dynamics of energy migration in the two photosystems. We present here a brief biography and comments on the work of Navasard Karapetyan. We remember him as an enthusiastic person who had an unflagging curiosity, energy and profound sincere interest in many aspects of photosynthesis research.


Chemoprevention of prostate cancer: an updated view.
To place chemoprevention of prostate cancer in current clinical context. Review of recently published updates of large, randomized, controlled trials of primary chemoprevention of prostate cancer. With extended post-intervention follow-up, SELECT demonstrated a 17% increased risk of prostate cancer relative to placebo in the vitamin E alone arm. Two other trials in men with high-grade PIN demonstrated no effect of selenium alone or in combination with soy and lycopene. Trials of 5α-reductase inhibitors show an approximate 25% relative risk reduction in men at average risk and in those with an "elevated" PSA and prior negative biopsy, but adoption of these agents in clinical practice has been limited by concerns over an apparently increased risk of high-grade disease. Primary prevention of prostate cancer remains an attractive goal because of its prevalence and treatment-related morbidity. Neither selenium nor vitamin E prevents prostate cancer. The benefit/risk ratio for 5α-reductase inhibitors can be improved by limiting their use to men at high risk.


Intestinal FABP2 A54T polymorphism: association with insulin resistance and obesity in women.
To assess the association between the Ala54Thr genetic polymorphism of the fatty acid-binding protein 2 (FABP2) gene with insulin resistance and obesity. According to a sampling scheme based on BMI, 33 adult obese women (BMI > or = 30) and 30 adult normal-weight women (BMI > 18.5 and < 25 kg/m(2)) were recruited for this study. Women with chronic inflammatory diseases or acute pathology were excluded. Glucose, insulin, leptin, lipids, and tumor necrosis factor alpha (TNF alpha) were measured in fasting plasma samples. Insulin resistance was estimated through the homeostasis model assessment for insulin resistance method. The Ala54Thr allelic variant was determined by polymerase chain reaction, followed by restriction fragment-length polymorphism analysis. The Thr54 allele was more frequent in obese than in nonobese women (47.0% vs. 31.7; p = 0.08). Among obese women, higher TNF alpha concentrations were found when comparing the Thr54/Thr54 genotype (30.0 +/- 7.1 pg/mL) with either the Ala54/Thr54 genotype (21.2 +/- 8.4 pg/mL) or the Ala54/Ala44 genotype (20.1 +/- 7.0 pg/mL) (p < 0.05). In addition, higher fasting plasma insulin and leptin levels were found among Thr54/Thr54 homozygotes compared with the other genotypes (p < 0.05). Our results suggest that the Ala54Thr polymorphism of the FABP2 gene is associated with obesity and insulin resistance. The effect of this polymorphism might be mediated by elevated production of TNF alpha.


Evaluation of thiol/disulfide homeostasis in rheumatoid arthritis and disease activity.
It has been suggested that the deterioration in the antioxidant defense system due to thiols may cause the pro-oxidant/antioxidant imbalance seen in rheumatoid arthritis (RA). This study was conducted to evaluate thiol/disulfide (-SH/-SS) homeostasis in patients with RA compared to healthy controls, and to validate the limited number of studies examining the relationship between Disease Activity Score-28 (DAS28) and thiol parameters. A total of 100 individuals (mean age: 46.3 ± 12.03) consisting of 86 females and 14 males were included in the RA group, and a total of 100 individuals (mean age: 43.3 ± 10.96 years) consisting of 78 females and 22 males were included in the control group. DAS28 was used to assess RA disease activity. -SH/-SS homeostasis parameters were measured using the automated spectrophotometric method described by Erel and Neselioğlu. While native thiol (-SH) (p:0.001), total thiol (-SH + -SS) (p < 0.0001) levels and -SH\(-SS + -SH) ratio (p: 0.018) were lower in the RA group compared to the healthy controls, disulfide (-SS) level (p: 0.005)), -SS\-SH (p: 0.001) and -SS\(-SS + -SH) (p: 0.002) ratios were found to be higher. In the control group and the group in remission (defined by DAS28 < 2.6), the median values of -SH (p:0.002) and -SS + -SH (p:0.0008) were found to be significantly higher, and the median value of -SS (p: 0.001) was found to be lower compared to the other DAS28 groups. While a negative correlation was found between DAS28 and -SH (r: -0.243, p: 0.007), a positive correlation was found between DAS28 and -SS (r: 0.316, p: 0.0003), -SS\-SH (r:0.229, p: 0.002) and -SS\(-SS + -SH) (r: 0.285, p: 0.0009). The plasma thiol antioxidant pool was decreased in RA compared to healthy controls and those with active disease compared to those in remission.


Biphasic solitary fibrous tumor of the orbit with distant metastases.
The aim of this study is to report the first case of biphasic solitary fibrous tumor (SFT) of the orbit with documented histological transformation and metastatic diffusion. We describe a case of a 23-year-old Caucasian man with recurrent SFT of the right orbit with intracranial invasion. The patient underwent surgical tumor removal via a right fronto-orbital approach. Histopathological examination showed a biphasic tumor pattern with both spindle cell and epithelioid components. The histopathological re-evaluation of previously removed lesions (1999 and 2004) confirmed the diagnosis of SFT, without any evidence of epithelioid component at that time. The patient developed local recurrence and systemic metastases (occipital foramen and clivus, paravertebral muscles and peritoneum) three years after surgery. We are unaware of previous reports of biphasic solitary fibrous tumor of the orbit with documented histological transformation and metastatic diffusion.


Prevalence of three-rooted mandibular permanent first and second molars in the Saudi population.
This study aims to explore the frequency and factors affecting the prevalence of an extra root in the lower first and second permanent molars in the Saudi population. Images of 379 Saudi patients who underwent CBCT for routine dental treatment were assessed. The CBCT images were evaluated on a 34-inch LED screen in a dark room and assessed by two examiners to count the prevalence of an additional root in the lower molars. Laterality and the gender factors were used to analyze that prevalence. Percentages represent categorical variables; Fisher's exact test and Chi square test were also used for the categorical variables. In the lower first molars, the prevalence of extra root in female patients was 5.7%, 3% in male patients and the overall prevalence was 3.05%; in lower second molars, the prevalence was 1.81% in female patients and 3.04% in male patients with an overall prevalence of 1.48%. A statistically significant difference was fond in the existence of an additional root with regard to laterality, to be more common on the right compared to the left side for both mandibular molars. The extra root prevalence was statistically significant in female patients at the first molar compared to male patients (p < 0.05). The overall of extra roots prevalence in the lower first and second molars in the Saudi population are 3.05% and 1.48%, respectively. Consideration and identification of this variation is essential to ensure successful endodontic treatment.


Regional and temporal changes in the pattern of X-chromosome replication during the early post-implantation development of the female mouse.
We have made a detailed study of the X-chromosome replication pattern during the period when X-inactivation is occurring in the mouse embryo. Our observations show unequivocal regionalization of the embryo with respect to the temporal X-chromosome. The switch from isocyclic to allocyclic replication occurs in the embryonic ectoderm at approximately 6 days of development and is random with respect to parental origin of the X-chromosome. In the extra-embryonic tissues, however, the switch to allocyclic replication has apparently occurred prior to 5.3 days of development and almost exclusively involves the paternally-derived X-chromosome. Since these findings are consistent with results obtained in biochemical studies of X-chromosome activity in female embryos, we conclude that there is a close temporal relationship between the cytogenetic and biochemical manifestations of the X-inactivation process. In addition, we have observed a pattern of early paternal X-chromosome replication, transitory in some cases, that is unique to extra-embryonic tissues. These results suggest that there may be some differences in the mechanism by which X-inactivation occurs in the extra-embryonic tissues as compared with the embryonic ectoderm.


Concurrent Prophylactic Mastectomy, Immediate Reconstruction, and Salpingo-Oophorectomy in High-Risk Patients: A Case Series.
There are limited data on coordinated breast and gynecological risk-reduction surgery for high-risk patients in Canada. Therefore, this study aims to evaluate the patient demographics, surgical details, and outcomes of prophylactic mastectomy (PM) with immediate reconstruction and bilateral salpingo-oophorectomy (BSO) in high-risk patients. We conducted a retrospective chart review at an academic center of patients who concurrently underwent PM with immediate reconstruction and laparoscopic BSO over a 7-year period (March 2010-February 2017) were identified. A total of 16 patients underwent PM with immediate reconstruction and concurrent BSO. The mean age at the time of surgery was 46.2 ± 6.6 years. Thirteen (81%) patients were carriers of the BRCA1 or BRCA2 mutation. Two patients had prophylactic surgical therapy for BRCA1 mutation and 14 (87.5%) patients had prior oncological treatment. The most common type of procedures performed were skin-sparing, nipple-sparing mastectomy (56.2%) and reconstruction with acellular dermal matrix and implants (43.8%). All patients underwent laparoscopic BSO. The average combined case time was 282.5 ± 81.3 minutes with an average postoperative hospital stay of 1.3 ± 0.5 days. Six (37.5%) patients presented with 30-day postoperative complications, with higher rates in the alloplastic group. There were no gynecological complications. In conclusion, our results demonstrate that a combined multidisciplinary surgical approach did not increase length of stay or 30-day complication rates. Furthermore, concurrent risk-reducing strategies are an effective option for patients at high risk of breast or ovarian cancer.


The choroid plexus as a target site for cadmium toxicity following chronic exposure in the adult mouse: an ultrastructural study.
The effects on the choroid plexus (CP) of chronic (22 weeks) exposure to 1, 10 or 100 ppm Cd2+ in the drinking water was studied in adult mice. The CP from these mice was examined using scanning and transmission electron microscopy. The mice receiving 10 or 100 ppm Cd2+ showed a dose dependent reduction in fluid intake and weight loss. The CP from animals receiving 100 ppm Cd2+ showed severe degenerative changes characterized by loss of microvilli, rupturing of the apical surface, increased cytoplasmic vacuolation and cellular debris. There was also an increase in cellular blebbing and increased dark/light cell ratio. Cerebrospinal fluid analysis revealed an increased protein content. The mice receiving 10 ppm Cd2+ showed similar but less severe degenerative changes. The 1 ppm Cd2+ group were indistinguishable from controls. These results suggest that it would be appropriate to examine CP function in individuals excessively exposed to Cd.


Synthesis and biological characteristics of the four stereoisomers of 99mTc-N,N'-bis-(mercaptoacetyl)-2,3-diaminopropanoate.
To study the differences in biological behaviour between the four stereoisomers of 99mTc-CO2-DADS we synthesized both the L- and D-isomer of N,N'-bis-(benzoylmercaptoacetyl)-2,3-diaminopropanoic acid ethyl ester. The N2S2 ligands were labelled with 99mTc by the dithionite reduction method in alkaline medium to hydrolyze the ester function. Each isomer yielded two diastereomeric 99mTc-complexes, that were separated by RP-HPLC to finally obtain the four isomers of 99mTc-CO2-DADS. The biodistribution of the isomers was determined in mice and a baboon. The study in mice indicates that only the LB-isomer is responsible for the high liver uptake reported for (DL)-99mTc-CO2-DADS-B (Fritzberg et al. J. Nucl. Med. 23, 592-598, 1982). The rate of renal extraction and hepatobiliary excretion of the three other isomers is comparable to that of [131I]o-I-hippurate. Baboon renograms for the LA- and DA-isomers are similar to that of [123I]o-I-hippurate. The renogram of the DB-isomer resembles more the 99mTc-DTPA renogram, whereas the LB-isomer exhibits a 99mTc-DMSA-like renal build-up. It appears that minor configurational changes can drastically alter the renal handling of these bisamide bisthiol 99mTc-tracer agents.


SUMOylation of AMPKα1 by PIAS4 specifically regulates mTORC1 signalling.
AMP-activated protein kinase (AMPK) inhibits several anabolic pathways such as fatty acid and protein synthesis, and identification of AMPK substrate specificity would be useful to understand its role in particular cellular processes and develop strategies to modulate AMPK activity in a substrate-specific manner. Here we show that SUMOylation of AMPKα1 attenuates AMPK activation specifically towards mTORC1 signalling. SUMOylation is also important for rapid inactivation of AMPK, to allow prompt restoration of mTORC1 signalling. PIAS4 and its SUMO E3 ligase activity are specifically required for the AMPKα1 SUMOylation and the inhibition of AMPKα1 activity towards mTORC1 signalling. The activity of a SUMOylation-deficient AMPKα1 mutant is higher than the wild type towards mTORC1 signalling when reconstituted in AMPKα-deficient cells. PIAS4 depletion reduced growth of breast cancer cells, specifically when combined with direct AMPK activator A769662, suggesting that inhibiting AMPKα1 SUMOylation can be explored to modulate AMPK activation and thereby suppress cancer cell growth.


Generation of multi-scrolls in corona virus disease 2019 (COVID-19) chaotic system and its impact on the zero-covid policy.
In this paper, we discussed the impossibility of achieving zero-covid cases per day for all time with the help of fuzzy theory, while how a single case can trigger chaotic situation in the nearby city is elaborated using multi-scrolls. To accomplish this goal, we consider the number of new cases per day; [Formula: see text] to be the preferred state variable by restricting its value to the interval (0, 1). One can need to think of [Formula: see text] as a member of a fuzzy set and provide that set with appropriate membership functions. Moreover, how a single incident in one city can spread chaos to other cities is also addressed at length, using multi-scroll attractors and the signal excitation function. In addition, a bifurcation diagram of daily new instances vs the parameter [Formula: see text] is shown, elaborating that daily new cases may show a decrease under strict rules and regulations, but can again lead to chaos. Apart from biologist, this paper can play vital role for engineers as well in a sense that, a signal function can be embedded in non-symmetric systems for the creation of multi-scroll attractors in all directions using a generalized algorithm that has been designed in the current work. Finally, it is our future target to show that the covid is leading towards influenza and will be no more dangerous as was in the past.


The role of infrarenal aortic side branches in the pathogenesis of endoleaks after endovascular aneurysm repair.
To investigate the relation between the number of preoperative patent side branches and the presence or absence of postoperative endoleaks, and to study the fate of patent branches after operation. Thirty consecutive patients were included. Cine mode viewing of axial CT angiography images was applied to detect infrarenal aortic side branches. The position of side branches relative to the renal arteries, branch patency and run-off pathways were studied. A total of 160 patent side branches were found. All patients had two or more patent side branches. A patent inferior mesenteric artery was found in 22/30 patients (73%). Postoperative CT scans revealed major endoleaks in five patients (16%) and minor endoleaks in eight (27%). There was no significant difference in the number of preoperative patent side branches in patients with a completely thrombosed aneurysm sac (five; range 2-8) compared to patients with postoperative endoleaks (six; range 3-9; p = 0.12). Backbleeding from patent side branches as the sole cause of endoleak was seen in one patient only (3.3%). Postoperative endoleaks are not related to the number of preoperative patent side branches. In patients without endoleaks, contrast enhancement of side branches was repeatedly seen in the vicinity of the aneurysm wall. Although close follow-up of these branches is warranted, they did not affect the outcome of endovascular aneurysm repair.


Gallium-67 scintigraphy in patients with hemochromatosis treated by deferoxamine.
Gallium scintigraphy was performed as an aid for determining the presence or absence of malignant neoplasm in two patients with hemochromatosis treated by deferoxamine. However, gallium scan images could not be obtained. So gallium scintigraphy was performed once more to investigate the cause of low activity. Both patients had heavy urinary excretion of gallium in the first 24 hrs after the injection, and activity was very low on the day of examination. This phenomenon may be attributed to the effect of deferoxamine which is highly bound to the gallium.


The quality and clinical applicability of recommendations in anxiety disorders guidelines: A systematic review of seventeen guidelines from seven countries.
Anxiety disorders are the most common mental disorders, for which some countries and organizations have developed guidelines. It is necessary to understand the quality of these guidelines. The relevant guidelines were searched systematically by five reviewers using Appraisal of Guidelines for Research and Evaluation (AGREE) II and AGREE Recommendation Excellence (AGREE-REX) instruments. The scores in each domain were descriptively analyzed, and guidelines from different countries were compared. Seventeen guidelines were included. The scores in the domains "rigor of development" and "applicability" were the lowest and ranged from 16% to 77% and 25% to 71%, respectively. The scores in the domains "implementability" and "values and preferences" were similar and ranged from 30% to 67% and 25% to 77%. In terms of the comparison among countries, the Canadian guidelines achieved the highest scores in many domains but only scored 43% in the domain of "values and preferences". The Indian guidelines scored less than 50% in many domains but achieved a high score of 83% in the domain "scope and purpose". Language restrictions may cause selection bias. Besides, insufficient reports may lead to deviation of assessment results. There was no obvious advantage in guidelines from different countries. There was still a lot of room for improvement in some domains, especially "applicability", "implementability", "rigor of development" and "values and preferences".


Ivermectin inhibits ovine ABCG2-mediated in vitro transport of meloxicam and reduces its secretion into milk in sheep.
The ATP-binding cassette transporter G2 (ABCG2) is an efflux protein involved in the bioavailability and secretion into milk of several compounds including anti-inflammatory drugs. The aim of this work was to determine the effect in sheep of an ABCG2 inhibitor, such as the macrocyclic lactone ivermectin, on the secretion into milk of meloxicam, a non-steroidal anti-inflammatory drug widely used in veterinary medicine, and recently reported as an ABCG2 substrate. In vitro meloxicam transport assays in ovine ABCG2-transduced cells have shown that ivermectin is an efficient inhibitor of in vitro transport of meloxicam mediated by ovine ABCG2, with a 75% inhibition in the transport ratio (24.85 ± 4.62 in controls vs 6.31 ± 1.37 in presence of ivermectin). In addition, the role of ovine ABCG2 in secretion into milk of meloxicam was corroborated using Assaf lactating sheep coadministered with ivermectin. Animals were administered subcutaneously with meloxicam (0.5 mg/kg) with or without ivermectin (0.2 mg/kg). No difference in plasma pharmacokinetic parameters was found between treatments. In the case of milk, a significant reduction in the area under concentration-time curve (AUC) (3.92 ± 0.66 vs 2.26 ± 1.52 μg·h/mL) and the AUC milk-to-plasma ratio (0.17 ± 0.03 vs 0.09 ± 0.06) was reported for ivermectin-treated animals compared to controls.


Mutagenicity to Salmonella, Drosophila and the mouse bone marrow of the human antineoplastic agent fotemustine: prediction of carcinogenic potency.
The antineoplastic agent fotemustine is shown to be a base-pair mutagen to Salmonella. Activity is more marked in the uvrB-proficient strain G46 than in the repair-deficient strain TA1535. This is consistent with its ability to cross-link DNA. Potent activity as a somatic and germ-cell mutagen to Drosophila was also observed. A potent clastogenic response was given by fotemustine in the mouse bone marrow following either oral gavage or intraperitoneal injection of a single dose of 5 mg/kg. In each of these respects it is shown to be indistinguishable from the structurally related antineoplastic agent and human carcinogen MeCCNU. It is concluded that fotemustine should be regarded as having clear potential to induce cancer in humans. Based on these data, including the preponderance of chromosome breakages over recessive lethal mutations in Drosophila, an estimated rodent carcinogenic potency (TD50) of between 15-150 mg/kg is suggested for fotemustine.


Reduction in movement-evoked pain and fatigue during initial 30-minute transcutaneous electrical nerve stimulation treatment predicts transcutaneous electrical nerve stimulation responders in women with fibromyalgia.
We previously showed that 1 month of transcutaneous electrical nerve stimulation (TENS) reduces movement-evoked pain and fatigue in women with fibromyalgia (FM). Using data from this study (Fibromyalgia Activity Study with TENS [FAST]), we performed a responder analysis to identify predictors of clinical improvement in pain and fatigue with TENS, validated these models using receiver operator characteristic, and determined number needed to treat and number needed to harm. Participants were randomly assigned to active-TENS (2-125 Hz; highest-tolerable intensity), placebo-TENS, or no-TENS for 1 month. At the end of the randomized phase, placebo-TENS and no-TENS groups received active-TENS for 1 month. The predictor model was developed using data from the randomized phase for the active-TENS group (n = 103) and validated using data from placebo-TENS and no-TENS groups after active-TENS for 1 month (n = 155). Participant characteristics, initial response to TENS for pain and fatigue, sleep, psychological factors, and function were screened for association with changes in pain or fatigue using a logistic regression model. Predictors of clinical improvement in pain were initial response to pain and widespread pain index (area under the curve was 0.80; 95% confidence interval: 0.73-0.87). Predictors of clinical improvement in fatigue were marital status, sleep impairment, and initial response to TENS (area under the curve was 0.67; 95% confidence interval: 0.58-0.75). Number needed to treat for pain and fatigue ranged between 3.3 and 5.3. Number needed to harm ranged from 20 to 100 for minor TENS-related adverse events. The response to an initial 30-minute TENS treatment predicts who responds to longer-term TENS use in women with FM, making this a clinically useful procedure. Number needed to treat and number needed to harm suggest that TENS is effective and safe for managing pain and fatigue in FM.


Epithelial properties of pleomorphic xanthoastrocytomas determined in ultrastructural and immunohistochemical studies.
Three cases of pleomorphic xanthoastrocytoma (PXA), one of which showed anaplastic evolution, are described. In all three the PXA tumors were well circumscribed and could be totally removed. Light-microscopically, pleomorphic tumor cells clustered gregariously and often formed alveolar structures. Electron microscopy revealed various epithelial properties, such as junctions and interdigitations between apposing tumor cells, and prominent basal laminae surrounding tumor nests. The circumscribed growth of PXA, as contrasted with an infiltrative growth of usual astrocytoma, can be attributed to the cellular cohesion based on the epithelial properties of the tumor cells. In the third patient, tumor recurred 6 months postoperatively. Although the recurrent tumor retained the alveolar structures, pleomorphism and various degenerative features of the tumor cells diminished with advance in the proliferative activities.


Iron treatment: impact of safety issues.
Improved outcomes result when a hemodialysis patient's hematocrit is increased to greater then 33%. The recent National Kidney Foundation Dialysis Outcomes Quality Initiative (NKF-DOQI) Anemia Panel recommended the use of intravenous (i.v.) iron therapy to increase hematocrits into this range. As the use of i.v. iron has increased, there has been an interest in more critically assessing the potential risks of such therapy. In this article, the possible risks are reviewed and considered in concert with the known benefits of iron treatment. A recommendation is made, in contrast to the NKF-DOQI Guidelines, that i.v. iron should not be administered to hemodialysis patients if the serum ferritin level if greater than 500 ng/mL.


SIMply Better Resolution in Live Cells.
Breaking the Abbe diffraction limit has opened the door to imaging the nanometer-scale structure of living cells with fluorescence. New advances have pushed the resolution of structured illumination microscopy even further to gently and rapidly image the complex molecular structure of the plasma membrane in living cells.


Combined Precursor Engineering and Grain Anchoring Leading to MA-Free, Phase-Pure, and Stable α-Formamidinium Lead Iodide Perovskites for Efficient Solar Cells.
α-Formamidinium lead iodide (α-FAPbI3 ) is one of the most promising candidate materials for high-efficiency and thermally stable perovskite solar cells (PSCs) owing to its outstanding optoelectrical properties and high thermal stability. However, achieving a stable form of α-FAPbI3 where both the composition and the phase are pure is very challenging. Herein, we report on a combined strategy of precursor engineering and grain anchoring to successfully prepare methylammonium (MA)-free and phase-pure stable α-FAPbI3 films. The incorporation of volatile FA-based additives in the precursor solutions completely suppresses the formation of non-perovskite δ-FAPbI3 during film crystallization. Grains of the desired α-phase are anchored together and stabilized when 4-tert-butylbenzylammonium iodide is permeated into the α-FAPbI3 film interior via grain boundaries. This cooperative scheme leads to a significantly increased efficiency close to 21 % for FAPbI3 perovskite solar cells. Moreover, the stabilized PSCs exhibit improved thermal stability and maintained ≈90 % of their initial efficiency after storage at 50 °C for over 1600 hours.


Crystal structure of (N^C) cyclo-metalated AuIII diazide at 100 K.
The title compound, an (N^C)-cyclo-metalated gold(III) diazide, namely, di-azido-[5-eth-oxy-carbonyl-2-(5-eth-oxy-carbonyl-pyridin-2-yl)phenyl-κ2 C 1,N]gold(III), [Au(C17H16NO4)(N3)2] or Au(ppyEt)(N3)2, was synthesized by reacting Au(ppyEt)Cl2 with NaN3 in water for 24 h. The complex has been structurally characterized and features a gold center with a square-planar environment. The Au-N(azide) bond lengths are significantly different depending on the influence of the atom trans to the azide group [Au-N(trans to C) of 2.067 (2) Å versus Au-N(trans to N) of 2.042 (2) Å]. The azide groups are twisted in-and-out of plane by 56.2 (2)°.


Incidental dural tears associated with worse clinical outcomes in patients operated for lumbar spinal stenosis.
Retrospective cohort study. Incidental dural (ID) tear is a common complication of spine surgery with a prevalence of 4-10%. The association between ID and clinical outcome is uncertain. Former studies found only minor differences in Oswestry Disability Index (ODI). We aimed to examine the association of ID with treatment failure after surgery for lumbar spinal stenosis (LSS). Between 2007 and 2017, 11,873 LSS patients reported to the national Norwegian spine registry (NORspine), and 8,919 (75.1%) completed the 12-month follow-up. We used multivariate logistic regression to study the association between ID and failure after surgery, defined as no effect or any degrees of worsening; we also compared mean ODI between those who suffered a perioperative ID and those who did not. The mean (95% CI) age was 66.6 (66.4-66.9) years, and 52% were females. The mean (95% CI) preoperative ODI score (95% CI) was 39.8 (39.4-40.1); all patients were operated on with decompression, and 1125 (12.6%) had an additional fusion procedure. The prevalence of ID was 4.9% (439/8919), and the prevalence of failure was 20.6% (1829/8919). Unadjusted odds ratio (OR) (95% CI) for failure for ID was 1.51 (1.22-1.88); p < 0.001, adjusted OR (95% CI) was 1.44 (1.11-1.86); p = 0.002. Mean postoperative ODI 12 months after surgery was 27.9 for ID vs. 23.6 for no ID. We demonstrated a significant association between ID and increased odds for patient-reported failure 12 months after surgery. However, the magnitude of the detrimental effect of ID on the clinical outcome was small.


Endothelial p21(WAF1/CiP1) cell cycle inhibitor is down-regulated in breast cancer.
Tumor angiogenesis is considered a multi-pathway process, while p21(WAF1/CiP1) is a CDK inhibitor involved in cell division and survivaL Herein the tumor environment effect on endothelial p21(WAF1/Cip1) expression is examined. The EA.hy 926 endothelial cell line and tumor-conditioned medium (TCM) from the MDA-MB-468 breast cancer cell line were used. Endothelial cells grown alone and in TCM were immunostained for p21(WAF1/Cip1) and analyzed by RT-PCR Forty-four cases of breast cancer and forty-three cases of normal breast tissue were immunostained for p21(WAF1/Cip1). Endothelial p21(WAF1/Cip1) is transcriptionally down-regulated under the influence of TCM. Moreover, it seems that breast cancer tumor endothelium does not express p21(WAF1/Cip1). P21(WAF1/Cip1) plays a major role in angiogenesis, since tumor cells seem to down-regulate endothelial p21(WAF1/Cip1), compared to endothelial cells grown in serum-free medium. The verification of the tissue culture experiment results by immunohistochemistry on tissue sections indicates p21(WAF1/Cip1) as a target of modern molecular therapy.


[The mechanism of the tetrazolium reduction and the effect of phenazinmethosulfate (author's transl)].
Modern results of the literature form the basis for the presentation of a scheme which shows the reduction of tetrazolium salts and the action of phenazine methosulfate under histochemical conditions. The reduction of tetrazolium salts passes the radical state and it hapens principally on the niveau of the flavin proteins and the ubiquinone. The importance of the superoxide radical for the reduction of tetrazolium salts under aerobic conditions is emphasized.


4-Aminobutyrate can be released exocytotically from guinea-pig cerebral cortical synaptosomes.
Guinea-pig synaptosomes possess two functional pools of 4-aminobutyrate (GABA). One is rapidly labelled by added [14C]GABA, is steadily released in a Ca2+-independent manner when the Na+ electrochemical potential across the plasma membrane is collapsed, and is depleted by the GABA analogue 2,4-diaminobutyrate (DABA), all of which is consistent with a cytosolic location. A second, noncytosolic compartment only slowly equilibrates with exogenous [14C]GABA, is not depleted by DABA, but can release 350 pmol of endogenous GABA/mg of protein (8% of the total intrasynaptosomal GABA) within 15 s of depolarization in the presence of Ca2+. Ca2+-independent release occurs by thermodynamic reversal of the plasma membrane uptake pathway following artifactually prolonged depolarization, whereas Ca2+-dependent release is consistent with physiological exocytosis from vesicular stores.


Interaction of the herbicide atrazine with model membranes. II: Effect of atrazine on fusion of phospholipid vesicles.
The effect of atrazine on Ca2+ induced fusion of cardiolipin(CL) and phosphatidylserine (PS) vesicles is studied by Tb3+/dipicolinic acid fluorescence and turbidity measurements. The interaction of herbicide with CL and PS membranes is studied by DPH fluorescence polarization. At low concentrations the pesticide partially inhibits fusion, especially in CL vesicles. Higher concentrations of atrazine decrease inhibition of fusion in CL, while fusion is slightly increased in PS. The Ca2(+)-induced increase of turbidity is not affected by atrazine in both PS and CL aggregation experiments. DPH polarization measurements show a perturbation only of the membrane hydrophobic core of PS, in presence of Ca2+. It is hypothesized that this biphasic effect shown by low and high atrazine concentrations on Ca2(+)-induced fusion of vesicles is due to a different localization of the pesticide in the membrane.


The COVID-19 Pandemic Vulnerability Index (PVI) Dashboard: Monitoring county-level vulnerability using visualization, statistical modeling, and machine learning.
While the COVID-19 pandemic presents a global challenge, the U.S. response places substantial responsibility for both decision-making and communication on local health authorities, necessitating tools to support decision-making at the community level. We created a Pandemic Vulnerability Index (PVI) to support counties and municipalities by integrating baseline data on relevant community vulnerabilities with dynamic data on local infection rates and interventions. The PVI visually synthesizes county-level vulnerability indicators, enabling their comparison in regional, state, and nationwide contexts. We describe the data streams used and how these are combined to calculate the PVI, detail the supporting epidemiological modeling and machine-learning forecasts, and outline the deployment of an interactive web Dashboard. Finally, we describe the practical application of the PVI for real-world decision-making. Considering an outlook horizon from 1 to 28 days, the overall PVI scores are significantly associated with key vulnerability-related outcome metrics of cumulative deaths, population adjusted cumulative deaths, and the proportion of deaths from cases. The modeling results indicate the most significant predictors of case counts are population size, proportion of black residents, and mean PM2.5. The machine learning forecast results were strongly predictive of observed cases and deaths up to 14 days ahead. The modeling reinforces an integrated concept of vulnerability that accounts for both dynamic and static data streams and highlights the drivers of inequities in COVID-19 cases and deaths. These results also indicate that local areas with a highly ranked PVI should take near-term action to mitigate vulnerability. The COVID-19 PVI Dashboard monitors multiple data streams to communicate county-level trends and vulnerabilities and facilitates decision-making and communication among government officials, scientists, community leaders, and the public to enable effective and coordinated action to combat the pandemic.


Bio-oil production and removal of organic load by microalga Scenedesmus sp. using culture medium contaminated with different sugars, cheese whey and whey permeate.
The objective of this study was to evaluate the bio-oil production and the organic load removal using the microalga Scenedesmus sp. The cultivation was carried out in reactors with a total volume of 3 L and 0.7 vvm aeration, with illumination in photoperiods of 12 h light/12 h dark for 12 days. The following sugar concentrations were tested: 2.5, 5.0 and 10 g/L of glucose, lactose, fructose and galactose with 10% inoculum volume. After experiments were performed with cheese whey in natura and cheese whey permeate with different lactose concentrations (1.5, 2.5, 3.5 and 5.0 g/L). In these experiments the inoculum concentrations were 10, 15, 20 and 30% (v/v). The results showed that this microalga was effective for the production of lipids when it was cultivated in medium with cheese whey in natura with 2.5 g/L of lactose and 20% inoculum (v/v). Using cheese whey in natura at the concentration of 3.5 g/L of lactose and 30% (v/v) of inoculum obtained 77.9% of TOC removal and 38.447 mg of TOC removed/mg oil produced. It was also observed that when there is increased production of bio-oil, there is less removal of organic matter. The addition of glucose, fructose or galactose in the medium did not enhance the production of bio-oil by Scenedesmus sp. when compared to lactose, but increased the organic matter removal.


Genetic analysis of Kashmiri Muslim population living in Pakistan.
The PowerPlex 16 amplification kit was used for the analysis of allele frequencies for the 15 STR loci (D3S1358, TH01, D21S11, D18S51, Penta E, D5S818, D13S317, D7S820, D16S539, CSF1PO, Penta D, vWA, D8S1179, TPOX and FGA) in unrelated, autochthonous healthy adults from Kashmiri refugee population in Pakistani Punjab (n=125). The allelic distributions were in Hardy-Weinberg equilibrium in all of loci examined except for the vWA locus. Forensic parameters were calculated and a comparison was made with geographically nearby populations.