[Chinese expert consensus on multidisciplinary management of malignant tumor-associated acute abdomen].
Malignant tumor-associated acute abdomen refers to a non-perioperative acute abdominal disease caused by malignant tumors or caused by various anti-tumor treatments with acute abdominal pain as the main clinical manifestation. It is often critical and even life-threatening. For patients with malignant tumor-associated acute abdomen, the occurrence and development of tumors and the evolution of acute complications are often causal to each other. Therefore, diagnosis and treatment of malignant tumor-associated acute abdomen usually require the surgery-based multidisciplinary treatment (MDT). According to imaging features and access to medical resources, oncologists and surgeons, working with other relevant professional teams need to develop the most appropriate treatment strategy through hierarchical management based on different oncology assessments and treatment goals. Yet there is no consensus on diagnosis and treatment of malignant tumor-associated acute abdomen. Therefore, Chinese College of Surgeons, Chinese Society for Clinical Oncologists, Chinese Society of Multidisciplinary Team, and the Chinese Journal of Gastrointestinal Surgery gathered multidisciplinary experts in China to discuss and develop the Chinese expert consensus on multidisciplinary management of malignant tumor-associated acute abdomen. This consensus consists of three parts, namely multidisciplinary diagnosis and evaluation, multidisciplinary prevention and treatment, and specific treatment of common malignant tumor-associated acute abdomen. The diagnosis and evaluation section mainly includes oncology, imaging diagnosis and surgical perioperative evaluation. The prevention and treatment section mainly includes the prevention of malignant tumor-associated acute abdomen, the principle of treatment based on surgery, anti-tumor therapy-induced acute abdomen, as well as the prevention and management of special biological types of malignant tumor-associated acute abdomen. The last part discusses specific treatment of malignant tumor-associated acute abdomen such as gastrointestinal obstruction (surgery, palliative care, endoscopic or interventional surgery), gastrointestinal perforation (perioperative and surgical treatment), gastrointestinal bleeding (medical treatment, endoscopic surgery, interventional surgery, and surgical treatment), biliary system-associated acute abdomen (treatment of acute cholangitis, acute cholecystitis, and gallbladder perforation), and rupture of liver cancer (general treatment, transarterial embolization, and surgical treatment). We hope this consensus will help clinicians to understand the multidisciplinary standardized diagnosis and treatment of patients with malignant tumor-associated acute abdomen and to serve as a practical reference.


Accuracy of serum luteinizing hormone and serum testosterone measurements to assess the efficacy of medical castration in prostate cancer patients.
Luteinizing hormone-releasing hormone (LH-RH) agonists are the standard for androgen deprivation therapy (ADT) in prostate cancer (PCa) patients. Current guidelines recommend serum testosterone measurement to assess the efficacy of ADT and to define castration resistance. However, serum testosterone does not reflect the exclusive effect of castration due to its extratesticular production. The aim of this study is to analyze if serum LH reflects better than serum testosterone the activity of LH-RH agonists. Serum LH and serum testosterone were measured with chemiluminescent immunoassay (CLIA) in a cohort study of 1091 participants: 488 PCa patients "on LH-RH agonists", 303 "off LH-RH agonist" in whom LH-RH agonists were withdrawn, and 350 men with PCa suspicion "no LH-RH agonist" who never received LH-RH agonists. In a validation cohort of 147 PCa patients, 124 on "LH-RH agonists" and 19 "off LH-RH agonists", serum testosterone was also measured with liquid chromatography and tandem mass spectrometry (LC MSMS). The area under the curve (AUC) to distinguish patients "on versus off LH-RH agonists" was 0.997 for serum LH and 0.740 for serum testosterone, P < 0.001. The 97.5 percentile of serum LH in patients "on LH-RH agonists" was 0.97 U/L, been the most efficient threshold 1.1 U/L. The AUCs for serum LH, testosterone measured with CLIA and with LC MSMS, in the validation cohort, were respectively 1.000, 0.646 and 0.814, P < 0.001. The efficacy to distinguish patients "on versus off LH-RH agonists" was 98.6%, 78.3%, and 89.5% respectively, using 1.1 U/L as threshold for serum LH and 50 ng/dL for serum testosterone regardless the method. Serum LH is more accurate than serum testosterone regardless the method, to distinguish patients "on versus off LH-RH agonists". The castrate level of serum LH is 1.1 U/l. These findings suggest that assessment of LH-RH agonist efficacy and castration resistance definition should be reviewed.


Effects of Abscisic Acid and Benzyladenine on Fruits of Normal and rin Mutant Tomatoes.
Since ethylene application did not induce ripening in detached fruits of the nonripening mutant rin we initiated studies to determine possible involvement of other hormones. We proposed that the lack of ripening in mutant rin tomato fruit may result from a lack of abscisic acid or from excessive endogenous levels of cytokiuin. Application of abscisic acid (3 x 10(-5)m and 10(-3)m) to detached fruits of a normal strain (Lycopersicon esculentum Mill. cv. ;Rutgers') reduced the time to initiate ripening by about 50%. This acceleration of the onset of ripening appeared not to be due to an increased rate of ethylene production. Abscisic acid did not alter respiration or ethylene production or induce ripening in rin fruit. Ripening in Rutgers fruit was not influenced by treatment with 6-benzyladenine (4.44 x 10(-6)m, 4.44 x 10(-5)m or 1.8 x 10(-4)m). Fruits of the mutant rin showed no response to exogenous BA. However, senescence rates of leaf disks of both Rutgers and rin were significantly inhibited by as little as 10(-7)m exogenous benzyladenine. The results are discussed in relation to previous studies of the physiology of rin fruits and it is concluded that endogenous levels of ABA and cytokinins do not account for the lack of ripening in rin fruit.


A romatic DNA adduct levels in human peripheral blood lymphocytes and total white blood cells by 32P postlabelling: need for validation.
Long lived lymphocytes tend to have higher 32P postlabelling measured levels of adducts than short lived granulocytes in environmental and life style associated i.e. smoking exposures. With the aim of investigating this issue for occupational exposure to PAH and contributing to further validation of some technical aspects of the 32P postlabelling assay, two Italian laboratories analysed PAH-DNA adducts from lymphocytes and total white blood cells WBC. Seventy seven blood samples from coke oven workers employed at a steel plant located in Taranto, Southern Italy, and 14 samples from control subjects were collected. At the University of Padua, DNA was purified from peripheral blood lymphocytes PBL. Two years later, at the University of Bari, white blood cells WBC were isolated from replicate blood samples stored at- 80 C and DNA purified by the same method. In both cases, the nuclease P1 modified postlabelling assay was used to determine aromatic DNA adduct levels. The mean adduct levels were 5.13 3.37 Padua and 2.48 1.27 Bari per 108 nucleotides. Both laboratories observed large inter individual variations of adduct levels ranging from 0.09 to 18.93 per 108 nucleotides. Both the correlation and the agreement of the two sets of data were assessed. Slight correlation r = 0.39; p 0.01 and a poor level of agreement were found, the intra class correlation coefficient being equal to 0.05. Better correlation coefficient r = 0.54, p 0.01 and intra class correlation coefficient r = 0.50 were observed comparing only the adduct levels determined on the diagonal zone DRZ. Our findings seem to confirm the same divergence reported in the literature on DNA adduct levels between lymphocytes and granulocytes.


Hartigan v. Zbaraz, 14 December 1987.
The Court affirmed by equally divided vote without comment the holding of Zbaraz vs. Hartigan in which the United States Court of Appeals, Seventh Circuit, had ruled that a twenty-four hour waiting period requirement for an abortion after parental notice was given was unconstitutional. The Court of Appeals had enjoined enforcement of provisions of a state statute authorizing petition of a Circuit Court as an alternative to giving parental notice until specific rules were promulgated assuring expeditious and confidential appeals.


The physiological basis for faster growth in the Sydney rock oyster, Saccostrea commercialis
Sydney rock oysters were sampled from a mass selection experiment for growth (the "selected" category) and from a control ("not selected") population and held in the laboratory at three ration levels. We evaluated three models to explain faster rates of growth by selected oysters. Selection resulted in oysters feeding at up to twice the rate and with greater metabolic efficiency than controls. A field experiment confirmed that selection leads to faster rates of feeding across a wide range of food concentrations. Selected oysters also grew more efficiently, at a smaller cost of growth (Cg): mean values for Cg were 0.43 J x J(-1) in selected individuals and 0.81 J x J(-1) in the controls. In contrast, oysters in both categories showed similar metabolic rates at maintenance, i.e., at a ration supporting zero growth. There was no evidence that differential energy allocation affected the balance between total metabolic requirements above and below zero net energy balance. By experimenting with selected and control oysters of different sizes and ages, then standardizing the data for size, we found no effects of age on the differences due to selection. Faster-growing oysters feed more rapidly; invest more energy per joule ingested; show a higher net growth efficiency; and are able to allocate less energy per unit of tissue growth, than slower-growing individuals.


Blood Group O Protect End-Stage Renal Disease Patients With Dialysis From Coronary Artery Disease.
Our study aims to investigate the role of the ABO blood group in the development and severity of coronary artery disease (CAD) in end-stage renal disease (ESRD) patients with dialysis. A total of 408 ESRD patients with dialysis between January 2010 and December 2020 were enrolled including 204 patients diagnosed with CAD undergoing coronary angiography for the first time, and baseline characteristics as well as Gensini score (GS) were collected. Logistic regression analysis and linear regression analysis were performed to evaluate the relation of ABO blood types to the risk and severity of CAD, respectively. Blood group O frequency was significantly low in dialysis ESRD patients with CAD (25 vs. 38.24%) compared with the non-CAD patients and multivariable logistic regression showed blood group O was negatively associated with the risk of CAD [adjusted odds ratio (OR) = 0.33, 95% CI = 0.19-0.60, p < 0.001] as well as the GS tertiles (adjusted OR = 0.23, 95% CI = 0.11-0.49, p < 0.001) compared with A blood group. Blood group A, B, and AB were positively associated with the high Gensini tertile compared with O blood group (adjusted OR = 4.26, 95% CI = 2.03-8.93, p < 0.001; adjusted OR = 2.39, 95% CI = 1.11-5.13, p < 0.05; adjusted OR = 4.33, 95% CI = 1.40-13.35, P < 0.05). Similarly, multivariable linear regression results revealed O blood type was negatively associated with the GS (β = -26.129, 95% CI = -40.094 to -12.164, p < 0.001). This case-control study demonstrated that blood group O was a potential independent protective factor for the risk and severity of CAD in ESRD patients with dialysis.


A field-programmable-gate-array based high time resolution arbitrary timing generator with a time folding method utilizing multiple carry-chains.
A carry-chain based high time resolution arbitrary timing generator, which is fully implemented using field-programmable-gate-array resources, is reported in this paper. The arbitrary timing generator channel operates with two alternative carry-chains to achieve non-dead-time timing sequence generation, and a 45.3 ps time resolution with a 383 ps minimum pulse width can be obtained. The time resolution is further improved to 11.3 ps by employing four parallel carry-chains in a single arbitrary timing generator channel to realize "time folding." The timing generator has a high time stability, and the time uncertainty is below 12 ps within a wide time range of 1 ns-108 ns. The arbitrary timing generator can be used to generate continuous spike timing sequences with a picosecond time resolution.


Structure and chromosomal localization of the human glycogenin-2 gene GYG2.
Glycogenin-2 is one of two self-glucosylating proteins involved in the initiation phase of the synthesis of the storage polysaccharide glycogen. Cloning of the human glycogenin-2 gene, GYG2, has revealed the presence of 11 exons and a gene of more than 46 kb in size. The structure of the gene explains much of the observed diversity in glycogenin-2 cDNA sequences as being due to alternate exon usage. In some cases, there is variation in the splice junctions used. Over regions of protein sequence similarity, the GYG2 gene structure is similar to that of the other glycogenin gene, GYG. A genomic GYG2 clone was used to localize the gene to Xp22.3 by fluorescence in-situ hybridization. Localization close to the telomere of the short arm of the X chromosome is consistent with mapping information obtained from glycogenin-2 STS sequences. Glycogenin-2 maps between the microsatellite anchor markers AFM319te9 (DXS7100) and AFM205tf2 (DXS1060), and its 3' end is 34.5 kb from the 3' end of the arylsulphatase gene ARSD. GYG2 is outside the pseudoautosomal region PAR1 but still in a region of X-Y shared genes. As is true for several other genes in this location, an inactive remnant of GYG2, consisting of exons 1-3, may be present on the Y chromosome.


Vancouver AIDS conference: special report. Three African countries to take part in trials to reduce mother-to-child transmission.
UNAIDS has announced that 1900 HIV-positive women in five sites in South Africa, Tanzania, and Uganda are to take part in a clinical trial to evaluate the efficacy and tolerance of three regimens for the prevention of mother-to-child (MTC) transmission of HIV in a population where breast-feeding is the norm. The regimens will use zidovudine in combination with 3TC, compared to a placebo. Some 3 million children are estimated to have been infected via MTC since the HIV epidemic started, and of these, 85% are in sub-Saharan Africa. HIV/AIDS prevalence among children in developing countries is about 35 times higher than in the industrialized world. A trial conducted in the US and France using zidovudine showed a 67% reduction in the risk of MTC transmission. But UNAIDS warns that the cost of this treatment, at about $1500 per mother-child pair, makes it impractical for widespread use in developing countries, where mothers tend to wait more than 30 weeks after birth for their first visit to a clinic, too late for the treatment to start. Breast feeding is another issue. For many mothers, the risk of their infant dying if not breast fed is greater than the risk of transmitting HIV by breast feeding. So the trial will try to ensure that any gains from early drug treatment are not simply lost again through losses due to breast feeding.


[Dynamic of immune response in primary cytomegalovirus infection and after reactivation of cytomegalovirus in patients with organ allotransplantation].
A total of 44 serum specimens from 7 patients with kidneys or liver transplanted from donors who had antibodies (Ab) to human cytomegalovirus (CMV) were studied. In 4 recipients anti-CMV Ab were found before transplantation and in 3 others they were not detected. It was shown by EIA that IgM and IgG anti-CMV appeared in the sera of primarily infected patients after 1-2 weeks and their titers were 5-10 times lower than in patients with reactivated CMV infection. Immunoblotting of Ab to individual CMV proteins showed a narrower spectrum of Ab during the initial period of primary CMV infection in comparison with the same period of reactivation and delayed production of AB to conformation-dependent determinants. Hence, analysis of anti-CMV Ab during the first 4-6 weeks after organ transplantation by EIA and immunoblotting differentiates primary CMV infection from its reactivation by Ab titers and spectrum. These parameters vary in some patients.


[Application of medical guidelines for the prescription of statins].
The efficacy of statins to prevent coronary heart disease (CHD) is well documented. This class of lipid-lowering drugs is now widely prescribed and was demonstrated to be cost effective in high risk patients. To assess the appropriateness of statins use, regarding initiation and follow-up of the treatment, as compared to the guidelines elaborated in 1996 by National Agency for the Development of Medical Evaluation (ANDEM). These guidelines were based on stratification of patients according to cardiovascular risk. Two groups of patients living in Ile-de-France region were defined, using Health Insurance computer database, on reimbursements. The first group named "new users" included patients in whom statin therapy was initiated during March 2000. The second group named "long term users" included patients who have been treated by statin therapy for one year or more. A sample of patients were randomly selected among these two groups. Trained Health Insurance advisors analyzed in depth the patients medical history and diet. All biological results were recorded and a complete history of medical therapy was assessed for each patient. An algorithm allowed the advisor to rate for nonadherence according to French medical guidelines. "New users": the random sample consisted of 460 patients, among whom 398 (87%) were free of CHD in whom the nonadherence rate was 72.4% (68.0% to 76.8%). Nonadherence concerned: LDL cholesterol level not tested (32%) and/or absence of prior fat-free diet (37%) and/or LDL cholesterol value before drug therapy was below the guidelines/threshold. "Long term users": the random sample consisted of 582 patients, among whom 381 (65%) were free of CHD. The nonadherence rate was 71.1% (66.5% to 75.7%). In addition, the nonadherence rate for patients in secondary prevention was 82.1% (79.7% to 84.6%) respectively, corresponding to: LDL cholesterol level not tested (41% and 34%); and/or no change dietary (18% and 12%); and/or unreach the LDL-C target level (24% and 45%). This study shows that the implementation of guidelines needs to be improved in clinical practice.


Women, marriage and family--traditionalism vs. modernity in Albania.
"The aim of the article is to illustrate how the transition from traditionalism to modernity in Albanian society is reflected in the fields of decision-making in choosing the marriage partner, arena of choosing the marriage partner, and factors of importance for harmony in the marital relationship. We also outline the changes in women's participation in productive work, in social and policy life, and in education. The empirical material stems from a survey conducted in Albania [in] 1984. The number of respondents was 1,303. We conclude that there is a strong modernistic tendency both with regard to choosing marriage partner and factors important for harmony. The main feature of the development in Albania is the rapidity and explicitness of changes in attitudes towards marriage and family and in women's position."


Testosterone and dihydrotestosterone modulate the redox homeostasis of endothelium.
The predominance of cardiovascular diseases among men compared to premenopausal women has been attributed to testosterone, which is implicated in vascular remodeling. Molecular mechanisms underlying its role have not been clarified but oxidative stress-induced inflammation may be important. We therefore investigated in vitro the effects of testosterone and dihydrotestosterone, (a nonaromatized androgen), on redox homeostasis in absence (basal conditions) and after corticotropin-releasing hormone-induced pro-oxidant action in macroendothelial cells. More specifically, we explored their role on well-established antioxidant enzymes activity, namely endothelial nitric oxide synthase, superoxide dismutase, catalase, and glutathione. We observed that both androgens significantly increased the intracellular reactive oxygen species levels, endothelial nitric oxide synthase activity, nitric oxide concentration as well as superoxide dismutase activity and decreased catalase activity. These effects of Testosterone and DHT were reversed in the presence of the androgen receptor antagonist, flutamide. Moreover, testosterone and dihydrotestosterone similarly enhanced the stimulatory effect of corticotropin-releasing hormone on intracellular reactive oxygen species levels and superoxide dismutase activity but did not influence the inhibitory effect on endothelial nitric oxide synthase activity, nitric oxide release and catalase activity. Finally, androgens did not have a detectable effect on glutathione levels or the glutathione/glutathione plus glutathione disulfide ratio. Our results reveal that testosterone and DHT rise the intracellular redox threshold of the endothelial cell and increases NO synthesis. These findings suggest that the action of testosterone is affected by the redox status of the endothelium and help to explain its controversial effects on the cardiovascular system.


Characterization of an eutherian gene cluster generated after transposon domestication identifies Bex3 as relevant for advanced neurological functions.
One of the most unusual sources of phylogenetically restricted genes is the molecular domestication of transposable elements into a host genome as functional genes. Although these kinds of events are sometimes at the core of key macroevolutionary changes, their origin and organismal function are generally poorly understood. Here, we identify several previously unreported transposable element domestication events in the human and mouse genomes. Among them, we find a remarkable molecular domestication that gave rise to a multigenic family in placental mammals, the Bex/Tceal gene cluster. These genes, which act as hub proteins within diverse signaling pathways, have been associated with neurological features of human patients carrying genomic microdeletions in chromosome X. The Bex/Tceal genes display neural-enriched patterns and are differentially expressed in human neurological disorders, such as autism and schizophrenia. Two different murine alleles of the cluster member Bex3 display morphological and physiopathological brain modifications, such as reduced interneuron number and hippocampal electrophysiological imbalance, alterations that translate into distinct behavioral phenotypes. We provide an in-depth understanding of the emergence of a gene cluster that originated by transposon domestication and gene duplication at the origin of placental mammals, an evolutionary process that transformed a non-functional transposon sequence into novel components of the eutherian genome. These genes were integrated into existing signaling pathways involved in the development, maintenance, and function of the CNS in eutherians. At least one of its members, Bex3, is relevant for higher brain functions in placental mammals and may be involved in human neurological disorders.


The alteration of left ventricular strain in later-onset spinal muscular atrophy children.
Patients with spinal muscular atrophy (SMA) may suffer from multisystem injury, including an impaired cardiovascular system. However, M-mode echocardiography, the current dominant echocardiographic modality, is limited in the detection of myocardial injury. We considered the use of left ventricular strain imaging in detecting myocardial injury and explored the serum lipid profile related to cardiovascular disease in later-onset SMA children. A case-control study involving 80 patients with later-onset SMA and 80 age-, gender-, and body surface area-matched control children was conducted in a single tertiary pediatric hospital in China. Data on the left ventricular strain measured using two-dimensional speckle tracking echocardiography, left ventricular function parameters assessed by M-mode echocardiography, and serum lipid profile of these two groups were retrospectively collected for differential analysis. The mean age of the 80 SMA patients were (6.87 ± 2.87) years, of which 46 were type 2 and 34 were type 3 patients. The global longitudinal strain (GLS) of the SMA group (-18.7 ± 2.9%, p < 0.001) was lower than that of the control group; the time to peak longitudinal strain (TTPLS) of the SMA group (22.9 ± 13.6 ms, p < 0.001) was higher than that of the control group, while left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), measured by the Teichholz method of M-mode echocardiography, showed no significant differences between the two groups. In addition, independent indicators for cardiovascular risk, including total cholesterol (TC)/HDL, low-density lipoprotein (LDL)/HDL, and Apo B/Apo A1 levels, were higher in SMA children than in the control group. Compared with healthy controls, later-onset SMA children presented with reduced GLS and prolonged TTPLS while the LVEF and LVFS values were within normal range. In particular, whether a reduced GLS or prolonged TTPLS in later-onset SMA compared to the control group can predict the risk of future cardiomyopathy remains to be investigated.


Erysipelothrix rhusiopathiae recruits host plasminogen via the major protective antigen SpaA.
Erysipelothrix rhusiopathiae is the causative agent of animal erysipelas and human erysipeloid. Some pathogenic bacteria are able to recruit host plasminogen and then use the plasminogen system for migration across tissue barriers or for nutritional demands during infection. However, there is no study on E. rhusiopathiae recruitment of plasminogen. SpaA has long been known to be a major protective antigen of E. rhusiopathiae, but its roles in virulence have not yet been well clarified. The aim of this study was to detect the activity of E. rhusiopathiae to recruit host plasminogen and evaluate the ability of SpaA to act as a receptor in the recruitment process. It was found that E. rhusiopathiae could recruit host plasminogen. SpaA could specifically bind host plasminogen. Anti-SpaA serum could significantly decrease the activity of E. rhusiopathiae to recruit plasminogen. In addition, this binding activity was lysine dependent. In conclusion, E. rhusiopathiae was able to recruit host plasminogen via SpaA. To our knowledge, this is the first report on E. rhusiopathiae recruitment of host plasminogen and the receptor in the process.


Cerebellar ataxia and peripheral neuropathy due to chronic bromvalerylurea poisoning.
A patient with chronic bromvalerylurea poisoning showed cerebellar ataxia and peripheral neuropathy. The patient was a 42-year-old Japanese man who developed consciousness disturbance, diplopia, slurred speech, ataxia and gait disturbance after having taken bromvalerylurea for ten years. Magnetic resonance imaging revealed atrophy of the cerebellum and pontine tegmentum. An electrophysiological study revealed decreased motor nerve conduction velocity and amplitude of compound muscle action potentials of the right tibial nerve. Histological findings of the left sural nerve indicated a slightly decreased large myelinated fiber diameter, which suggested chronic axonal damage.


Hydatid Pulmonary Embolism: A Case Report and Literature Review.
BACKGROUND Infection with Echinococcus granulosus is endemic in sheep and dogs in Central Asia, including Tibet. In humans, ingested parasites from the gastrointestinal system enter the liver via the portal vein. Rarely, hepatic hydatid cysts can rupture into the portal vein and embolize to the lungs. This report is of a 58-year-old woman with liver cysts and a pulmonary embolism due to hydatid disease. CASE REPORT We present a rare case of a pulmonary embolism caused by a hydatid cyst. A 58-year-old woman from the Tibet Autonomous Region of China was admitted to the hospital with symptoms of chest and back pain and shortness of breath within the previous 6 months. She had a 5-year history of hepatic echinococcosis. During hospitalization, the patient reported having aggravated chest and back pain and she developed a new symptom of hemoptysis. A pulmonary embolism was confirmed by computed tomography pulmonary angiography. After a multidisciplinary consultation, and based on the patient's medical history, clinical manifestations, laboratory test results, and imaging findings, a diagnosis of a pulmonary embolism caused by a hydatid cyst was established. CONCLUSIONS This report shows the importance of imaging findings in diagnosing a non-thrombotic pulmonary embolism due to hepatic hydatid disease. In this case, early and accurate diagnosis resulted in appropriate treatment with multidisciplinary patient management.


Enhanced electromagnon excitations in Nd-doped BiFeO3 nanoparticles near morphotropic phase boundaries.
In multiferroics, electromagnons have been recognized as a noticeable topic due to their indispensable role in magnetoelectric, magnetodielectric, and magnetocapacitance effects. Here, the electromagnons of Bi1-xNdxFeO3 (x = 0-0.2) nanoparticles are studied via terahertz time-domain spectroscopy, and the impacts of doping concentrations on electromagnons have been discussed. We found that the electromagnons in Bi1-xNdxFeO3 nanoparticles are associated with their phase transition. The total coupling weight of electromagnons is gradually increased in polar R3c structures and then reduces in the antipolar Pbam phase, and the weight in the antipolar phase is less than that of the pure R3c phase. Interestingly, a colossal electromagnon is observed at polar-antipolar and antiferromagnetic-ferromagnetic phase boundaries. Our work offers an avenue for designing and choosing materials with better magnetodielectric and magnetocapacitance properties.


Spontaneous activity in the inferior colliculus of CBA/J mice after manipulations that induce tinnitus.
Several physiological studies have linked experimentally induced tinnitus to increases in the spontaneous activity of auditory neurons. These results have led to the proposal of hyperactivity models of tinnitus in which elevated neural activity in the absence of auditory stimulation is perceived as phantom sound. Such models are appealing in their simplicity but remain controversial because a generalized elevation of spontaneous rates may not be observed after treatments that induce tinnitus in humans and experimental animals. Our study addressed these issues by characterizing the effects of common methods of tinnitus induction on spontaneous activity in the central nucleus of the inferior colliculus (ICC). The ICC is an interesting structure in tinnitus research because its diverse inputs include putative generator sites in the dorsal cochlear nucleus, as well as brainstem sources that appear to remain normal after tinnitus induction. Groups of CBA/J mice were subjected to one of three induction methods: bilateral or unilateral sound exposure, and acute salicylate intoxication. Relative to normal baselines, bilaterally exposed mice showed increases in the spontaneous rates of neurons with tuning near the exposure frequency. When the sample was separated into physiologically defined response classes, exposure effects were strongest among neurons with broad excitatory bandwidths. By contrast, salicylate decreased the spontaneous rates of low-frequency neurons with transient sound-evoked activity. Our results suggest that the disordered processes of hearing that give rise to tinnitus do not involve a pervasive elevation of spontaneous activity or a single mode of induction.


Tibial slope and high tibial osteotomy using the circular external fixator.
Alteration of tibial slope is one of the important anatomical changes of the proximal tibia after high tibial osteotomy. Increased or decreased tibial slope can effect further total knee prosthesis procedure. In this retrospective study, 18 knees of 17 patients (17 female, mean age 51 range 43-61, mean BMI is 33.6 +/- 4.6 kg/m2) who were applied high tibial osteotomy using circular external fixator due to medial compartment arthrosis of the knee were evaluated in terms of tibial slope changes. While mean correction about 12.3 degrees in mechanical femoro-tibial angle was obtained in frontal plan (P = 0.0001), significant change in tibial slope was not determined in sagittal plan (P = 0.127). The mean posterior proximal femoral angle values were measured as 79.5 +/- 2.1 degrees preoperatively and as 80.3 +/- 2.7 degrees postoperatively and found to fall into the normal range (80.4 +/- 1.6 degrees). As there is no significant alteration in tibial slope after high tibial osteotomy performed with the Ilizarov system, complications due to alteration in tibial slope will not be experienced in follow-up or in further total knee prosthesis procedure.


A model of the effects of cancer cell motility and cellular adhesion properties on tumour-immune dynamics.
We present a three-dimensional model simulating the dynamics of an anti-cancer T-cell response against a small, avascular, early-stage tumour. Interactions at the tumour site are accounted for using an agent-based model (ABM), while immune cell dynamics in the lymph node are modelled as a system of delay differential equations (DDEs). We combine these separate approaches into a two-compartment hybrid ABM-DDE system to capture the T-cell response against the tumour. In the ABM at the tumour site, movement of tumour cells is modelled using effective physical forces with a specific focus on cell-to-cell adhesion properties and varying levels of tumour cell motility, thus taking into account the ability of cancer cells to spread and form clusters. We consider the effectiveness of the immune response over a range of parameters pertaining to tumour cell motility, cell-to-cell adhesion strength and growth rate. We also investigate the dependence of outcomes on the distribution of tumour cells. Low tumour cell motility is generally a good indicator for successful tumour eradication before relapse, while high motility leads, almost invariably, to relapse and tumour escape. In general, the effect of cell-to-cell adhesion on prognosis is dependent on the level of tumour cell motility, with an often unpredictable cross influence between adhesion and motility, which can lead to counterintuitive effects. In terms of overall tumour shape and structure, the spatial distribution of cancer cells in clusters of various sizes has shown to be strongly related to the likelihood of extinction.


Fetal cells in a transcervical cell sample collected at 5 weeks of gestation.
Transcervical cell (TCC) sampling is being investigated as a promising method for obtaining fetal cells for prenatal genetic diagnosis. The present case report describes the identification of fetal cells by both fluorescent in situ hybridisation (FISH) and quantitative fluorescent polymerase chain reaction (QF-PCR) analyses in a TCC sample collected by intrauterine lavage at 5 + 0 weeks. This finding underscores the possible relevance of TCC sampling for extremely early prenatal genetic diagnosis.


Potential of modeling and simulations of bioengineered devices: Endoprostheses, prostheses and orthoses.
Modeling and simulation of prosthetic devices are the new tools investigated for the production of total customized prostheses. Computational simulations are used to evaluate the geometrical and material designs of a device while assessing its mechanical behavior. Data acquisition through magnetic resonance imaging, computed tomography or laser scanning is the first step that gives information about the human anatomical structures; a file format has to be elaborated through computer-aided design software. Computer-aided design tools can be used to develop a device that respects the design requirements as, for instance, the human anatomy. Moreover, through finite element analysis software and the knowledge of loads and conditions the prostheses are supposed to face in vivo, it is possible to simulate, analyze and predict the mechanical behavior of the prosthesis and its effects on the surrounding tissues. Moreover, the simulations are useful to eventually improve the design (as geometry, materials, features) before the actual production of the device. This article presents an extensive analysis on the use of finite element modeling for the design, testing and development of prosthesis and orthosis devices.


A novel, "double-clamp" binding mode for human heme oxygenase-1 inhibition.
The development of heme oxygenase (HO) inhibitors is critical in dissecting and understanding the HO system and for potential therapeutic applications. We have established a program to design and optimize HO inhibitors using structure-activity relationships in conjunction with X-ray crystallographic analyses. One of our previous complex crystal structures revealed a putative secondary hydrophobic binding pocket which could be exploited for a new design strategy by introducing a functional group that would fit into this potential site. To test this hypothesis and gain further insights into the structural basis of inhibitor binding, we have synthesized and characterized 1-(1H-imidazol-1-yl)-4,4-diphenyl-2-butanone (QC-308). Using a carbon monoxide (CO) formation assay on rat spleen microsomes, the compound was found to be ∼15 times more potent (IC(50) = 0.27±0.07 µM) than its monophenyl analogue, which is already a potent compound in its own right (QC-65; IC(50) = 4.0±1.8 µM). The crystal structure of hHO-1 with QC-308 revealed that the second phenyl group in the western region of the compound is indeed accommodated by a definitive secondary proximal hydrophobic pocket. Thus, the two phenyl moieties are each stabilized by distinct hydrophobic pockets. This "double-clamp" binding offers additional inhibitor stabilization and provides a new route for improvement of human heme oxygenase inhibitors.


Immediate total tooth replacement.
Successful implant placement at the time of extraction has been documented. Implant placement at the time of extraction was initially performed as a two-stage procedure often with barrier membranes and sophisticated second-stage surgical uncoverings. The authors describe the next generation of this technique, including atraumatic tooth removal with simultaneous root form, implant placement, and temporization at one appointment. This technique of "Immediate Total Tooth Replacement" allows for the maintenance of the bony housing and soft-tissue form that existed before extraction, while at the same time establishing a root form anchor in the bone for an esthetic restoration.


Sex differences in treatment and outcomes of patients with in-hospital ST-elevation myocardial infarction.
Two cohorts face high mortality after ST-elevation myocardial infarction (STEMI): females and patients with in-hospital STEMI. The aim of this study was to evaluate sex differences in ischemic times and outcomes of in-hospital STEMI patients. Consecutive STEMI patients treated with percutaneous coronary intervention (PCI) were prospectively recruited from 30 hospitals into the Victorian Cardiac Outcomes Registry (2013-2018). Sex discrepancies within in-hospital STEMIs were compared with out-of-hospital STEMIs. The primary endpoint was 12-month all-cause mortality. Secondary endpoints included symptom-to-device (STD) time and 30-day major adverse cardiovascular events (MACE). To investigate the relationship between sex and 12-month mortality for in-hospital versus out-of-hospital STEMIs, an interaction analysis was included in the multivariable models. A total of 7493 STEMI patients underwent PCI of which 494 (6.6%) occurred in-hospital. In-hospital versus out-of-hospital STEMIs comprised 31.9% and 19.9% females, respectively. Female in-hospital STEMIs were older (69.5 vs. 65.9 years, p = .003) with longer adjusted geometric mean STD times (104.6 vs. 94.3 min, p < .001) than men. Female versus male in-hospital STEMIs had no difference in 12-month mortality (27.1% vs. 20.3%, p = .92) and MACE (22.8% vs. 19.3%, p = .87). Female sex was not independently associated with 12-month mortality for in-hospital STEMIs which was consistent across the STEMI cohort (OR: 1.26, 95% CI: 0.94-1.70, p = .13). In-hospital STEMIs are more frequent in females relative to out-of-hospital STEMIs. Despite already being under medical care, females with in-hospital STEMIs experienced a 10-min mean excess in STD time compared with males, after adjustment for confounders. Adjusted 12-month mortality and MACE were similar to males.


Prone positioning in patients with acute respiratory distress syndrome: the Vollman Prone Positioner.
ARDS continues to be associated with high mortality rates despite numerous advances in critical care. Improvements in oxygenation can be achieved by placing patients with ARDS prone. The Vollman Prone Positioner offers an easy, safe, and inexpensive method to turn patients prone (for more information: www.vollman.com).


Measurement and removal of adherent endotoxin from titanium particles and implant surfaces.
Aseptic loosening is thought to be due primarily to osteolysis induced by cytokines and prostaglandins that are produced in response to implant-derived wear particles. Because endotoxin has many of the same effects as have been reported for wear particles, we hypothesized that adherent endotoxin may be responsible for the biological responses induced by wear particles. We demonstrated the presence of significant levels of adherent endotoxin on commonly used preparations of titanium particles as well as on titanium and titanium-alloy implant surfaces. In contrast, supernatants obtained by centrifugation of particle suspensions contained approximately 1% as much endotoxin as did the particles. Therefore, it is erroneous to assume that particles do not contain endotoxin on the basis of data that it cannot be detected in their supernatants or filtrates. These results emphasize the importance of considering the potential role of adherent endotoxin when examining the in vitro effects of wear particles and the in vivo performance of orthopaedic implants. We also developed a protocol that removed more than 99.94% of the adherent endotoxin from the titanium particles without detectably affecting their size or shape. The removal of adherent endotoxin will allow comparison of the biological responses induced by particles with or without adherent endotoxin.


Construction of a combinatorial IgE library from an allergic patient. Isolation and characterization of human IgE Fabs with specificity for the major timothy grass pollen allergen, Phl p 5.
To characterize human IgE antibodies with specificity for a major allergen at the molecular level, we have constructed an IgE combinatorial library from a grass pollen allergic patient. cDNAs coding for IgE heavy chain fragments and for light chains were reverse-transcribed and polymerase chain reaction-amplified from RNA of peripheral blood lymphocytes and randomly combined in plasmid pComb3H to yield a combinatorial library of 5 x 10(7) primary clones. IgE Fabs with specificity for Phl p 5, a major timothy grass pollen allergen, were isolated by panning. Sequence analysis showed that the 4 of the Fabs used the same heavy chain fragments which had combined with different kappa light chains. Soluble recombinant IgE Fabs were purified by affinity chromatography to Phl p 5 and, like natural IgE antibodies, cross-reacted with group 5 allergens from different grass species. The described approach should facilitate studies on the molecular interaction between IgE antibodies and allergens and encourages the consideration of specific IgE Fabs that are capable of interfering with allergen-IgE binding as potential therapeutic tools.


Value of Endometrial Echopattern at HCG Administration Day in Predicting IVF Outcome.
Assisted reproductive treatment (ART) cycle is an expensive procedure with low implantation and pregnancy rate; therefore, it is necessary to evaluate the predictors of success in these patients. The relationship between endometrial echopattern and pregnancy rate was evaluated. The endometrial echopattern was analyzed prospectively on the day of human chorionic gonadotropin (HCG) administration in 280 in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles with 8-14 mm endometrial thickness at Royan institute in 2013-2014. Based on echopattern, three groups were developed: pattern A (Triple line), pattern B (Heterogeneous-echogen) and pattern C (Homogeneous-echogen). Pregnancy rate (PR) was compared between all groups. Data was analyzed using SPSS (v.18, Chicago, IL, USA), and descriptive tests such as Chi-square and analytical tests like logistic regression, for controlling confounder variables like age. Among 280 patients finally evaluable, the distribution of endometrial echopattern on the day of HCG administration was 127 patients (45.4%) in group A, 98 patients (35%) in group B and 55 patients (19.6%) in group C. The highest PR per transfer pertained to group A (49.6%), and the lowest to group B (32.7%). The presence of pattern A (Triple line) appears more likely to favor pregnancy. Therefore, ultrasonographic evaluation of endometrial echopattern on the day of HCG administration has prognostic value in clinical settings for predicting implantation in ART cycle.


Facilitating [corrected] More Efficient Negotiations for Innovative Therapies: A Value-Based Negotiation Framework.
An increasing number of innovative therapies (e.g., gene- and cell-based treatments) have been developed in the past 20 years. Despite the significant clinical potential of these therapies, access delays may arise because of differing perspectives of manufacturers and payers regarding issues such as the value of the product, clinical and financial uncertainties, and sustainability.Managed entry agreements (MEAs) can enable access to treatments that would not be reimbursed by conventional methods because of such concerns. However, although MEA typologies exist, there is currently no structured process to come to agreements on MEAs, which can be difficult to decide upon and implement.To facilitate more structured MEA negotiations, we propose a conceptual "value-based negotiation framework" with corresponding application tools. The framework was developed based on an iterative process of scientific literature review and expert input. The framework aims to (i) systematically identify and prioritize manufacturer and payer concerns about a new treatment, and (ii) select a mutually acceptable combination of MEA terms that can best address priority concerns, with the lowest possible implementation burden. The proposed framework will be tested in practice, and is a step toward supporting payers and manufacturers to engage in more structured, transparent negotiations to balance the needs of both sides, and enabling quicker, more transparent MEA negotiations and patient access to innovative products.


Diffusion-weighted imaging in acute hyperammonemic encephalopathy.
Magnetic resonance imaging (MRI) findings associated with chronic liver disease are characterized by cerebral atrophy and bilateral, symmetric hyperintensities of the globus pallidus on T1-weighted images without corresponding signal intensities in T2-weighted images. Recently, distinct MRI changes of acute hepatic encephalopathy have been described which may be misinterpreted given their resemblance to hypoxic-ischemic injury imaging changes as well as their limited description in the neurologic literature. We describe 3 cases of acute hyperammonemic encephalopathy primarily characterized by restricted diffusion involving the insular and cingulate cortices and thalamus bilaterally.


Reduced activity of acetylcholinesterase in canine tracheal smooth muscle homogenates after active immune-sensitization.
Previous investigations have suggested that immune-sensitization increases airway smooth muscle responsiveness to cholinomimetic stimulation by reducing the rate of degradation of acetylcholine. To examine the hypothesis that increased cholinomimetic responsiveness of tracheal smooth muscle (TSM) caused by immune-sensitization results from inhibition of acetylcholinesterase (AChase) activity, we developed a method for direct measurement of AChase activity in homogenates of TSM obtained from mongrel dogs actively sensitized in vivo to ragweed pollen extract (n = 7) and sham-sensitized littermate controls (n = 7). For both sensitized and control specimens, saturation of AChase was obtained at approximately 3.12 mM substrate (acetylthiocholine); however, maximal enzyme activity in homogenates of ragweed-sensitized tissues was significantly less (0.862 +/- 0.088 absorbance units/min/mg protein [AU/min/mg]) compared to control homogenates (1.590 +/- 0.129 AU/min/mg; P less than 0.001). Kinetic analysis (Eadie-Hofstee plot) indicated similar Michaelis constants (Km) for AChase from ragweed-sensitized (0.360 +/- 0.063) and control (0.336 +/- 0.062) homogenates (P = NS). The concentration of physostigmine eliciting half-maximal inhibition (Ki) of AChase activity also was similar for tissues from sensitized (-7.92 +/- 0.032 log M) and control animals (-7.86 +/- 0.012 log M; P = NS). Pretreatment with selected mediators of anaphylaxis (10(-4) M histamine, 10(-6) M serotonin, 10(-5) M prostaglandin E2, 10(-6) M prostaglandin F2 alpha, and 10(-7) M leukotriene D4) did not affect AChase activity. Our data demonstrate reduced AChase activity in homogenates of canine TSM after active immune-sensitization in vivo. This corresponds to functional augmentation of cholinomimetic contraction in actively sensitized tissues.


Checks and balances in membrane phospholipid class and acyl chain homeostasis, the yeast perspective.
Glycerophospholipids are the most abundant membrane lipid constituents in most eukaryotic cells. As a consequence, phospholipid class and acyl chain homeostasis are crucial for maintaining optimal physical properties of membranes that in turn are crucial for membrane function. The topic of this review is our current understanding of membrane phospholipid homeostasis in the reference eukaryote Saccharomyces cerevisiae. After introducing the physical parameters of the membrane that are kept in optimal range, the properties of the major membrane phospholipids and their contributions to membrane structure and dynamics are summarized. Phospholipid metabolism and known mechanisms of regulation are discussed, including potential sensors for monitoring membrane physical properties. Special attention is paid to processes that maintain the phospholipid class specific molecular species profiles, and to the interplay between phospholipid class and acyl chain composition when yeast membrane lipid homeostasis is challenged. Based on the reviewed studies, molecular species selectivity of the lipid metabolic enzymes, and mass action in acyl-CoA metabolism are put forward as important intrinsic contributors to membrane lipid homeostasis.


Oocyte cohesin expression restricted to predictyate stages provides full fertility and prevents aneuploidy.
To ensure correct meiotic chromosome segregation, sister chromatid cohesion (SCC) needs to be maintained from its establishment in prophase I oocytes before birth until continuation of meiosis into metaphase II upon oocyte maturation in the adult. Aging human oocytes suffer a steep increase in chromosome missegregation and aneuploidy, which may be caused by loss of SCC through slow deterioration of cohesin [1-3]. This hypothesis assumes that cohesin expression in embryonic oocytes is sufficient to provide adequate long-term SCC. With increasing age, mouse oocytes deficient in the meiosis-specific cohesin SMC1β massively lose SCC and chiasmata [3, 4]. To test the deterioration hypothesis, we specifically and highly efficiently inactivated the mouse Smc1β gene at the primordial follicle stage shortly after birth, when oocytes had just entered meiosis I dictyate arrest. In the adult, however, irrespective of oocyte age, chiasma positions and SCC are normal. Frequency and size of litters prove full fertility even in aged females. Thus, SMC1β cohesin needs only be expressed during prophase I prior to the primordial follicle stage to ensure SCC up to advanced age of mice.


Rat testis mitochondrial phospholipid hydroperoxide glutathione peroxidase does not protect endogenous vitamin E against Fe2+-induced (lipo)peroxidation.
Rat testis mitochondria contain large amounts of both seleno-enzyme phospholipid hydroperoxide glutathione peroxidase (EC 220.127.116.11, PHGPx) and alpha-tocopherol. The scavenger role of vitamin E consists of transforming the lipoperoxyl radicals into lipid hydroperoxides, thus interrupting the peroxidative cascade. These hydroperoxides are in turn substrates of the PHGPx, which is considered one of the most important specific enzymes capable of protecting, in situ, the membranes from lipid peroxidation. A connection or synergism could, therefore, be envisaged between vitamin and enzyme opposing lipid damage in the mitochondria. Here we present data concerning the HPLC evaluation of vitamin E consumption in rat testis mitochondria and mitochondrial membranes, under different conditions of PHGPx activity, after Fe2+-induced lipid peroxidation. We have found that the enzyme activity, under the conditions tested, does not spare vitamin E from its peroxidation, therefore indicating that the postulated synergism between PHGPx and alpha-tocopherol can be excluded in rat testis mitochondria.


Intranasal ketamine for acute traumatic pain in the Emergency Department: a prospective, randomized clinical trial of efficacy and safety.
Ketamine has been well studied for its efficacy as an analgesic agent. However, intranasal (IN) administration of ketamine has only recently been studied in the emergency setting. The objective of this study was to elucidate the efficacy and adverse effects of a sub-dissociative dose of IN Ketamine compared to IV and IM morphine. A single-center, randomized, prospective, parallel clinical trial of efficacy and safety of IN ketamine compared to IV and IM morphine for analgesia in the emergency department (ED). A convenience sample of 90 patients aged 18-70 experiencing moderate-severe acute traumatic pain (≥80 mm on 100 mm Visual Analog Scale [VAS]) were randomized to receive either 1.0 mg/kg IN ketamine, 0.1 mg/kg IV MO or 0.15 mg/kg IM MO. Pain relief and adverse effects were recorded for 1 h post-administration. The primary outcome was efficacy of IN ketamine compared to IV and IM MO, measured by "time-to-onset" (defined as a ≥15 mm pain decrease on VAS), as well as time to and degree of maximal pain reduction. The 3 study groups showed a highly significant, similar maximal pain reduction of 56 ± 26 mm for IN Ketamine, and 59 ± 22 and 48 ± 30 for IV MO and IM MO, respectively. IN Ketamine provided clinically-comparable results to those of IV MO with regards to time to onset (14.3 ± 11.2 v. 8.9 ± 5.6 min, respectively) as well as in time to maximal pain reduction (40.4 ± 16.3) versus (33.4 ± 18), respectively. IN ketamine shows efficacy and safety comparable to IV and IM MO. Given the benefits of this mode of analgesia in emergencies, it should be further studied for potential clinical applications. Retrospectively registered on 27 June 2016. ClinicalTrials.gov ID: NCT02817477.


Sexual dysfunction in Chinese women at different reproductive stages and the positive effect of hormone replacement therapy in the early postmenopause.
The aims of the study were to investigate female sexual dysfunction (FSD) at different reproductive stages and the effect on FSD of hormone replacement therapy (HRT). Participants (N = 524) were divided into six groups according to the Stages of Reproductive Aging Workshop (STRAW + 10): reproductive age (R), early (ET)/late (LT) menopausal transition, early (EP)/late (LP) postmenopause and early postmenopause in women using HRT (EP-HRT; oestradiol sequentially combined with dydrogesterone). The Female Sexual Function Index (FSFI) was used to assess FSD. Univariate and multivariate logistic regression analysis was carried out to predict FSD risk factors. There was an increase in FSD in groups EP and LP, but not in groups R, ET and LT; most FSFI scores were lower in groups EP and LP than in groups R, ET and LT (p < .05). There was no difference in FSD between groups EP and LP, but lubrication and pain scores were higher in group EP (p < .05). The prevalence of FSD was lower in group EP-HRT; most FSFI scores were higher in group EP-HRT compared with group EP as control (p < .05). Further risk factors for FSD were identified as neutral and dissatisfied marital relations, lower educational level and smoking (p < .05). We report a clear association between deteriorating sexual function and increasing STRAW + 10 classification, suggesting the consequence of decreasing ovarian function. HRT containing 'natural hormones' was shown to have a beneficial effect on FSD. The results are reported here for the first time in Chinese women.


Diffuse pulmonary arteriovenous malformations: characteristics and prognosis.
To study the clinical characteristics and prognosis of patients with diffuse pulmonary arteriovenous malformations (AVMs). Retrospective chart review of all patients (n = 16) with diffuse pulmonary AVMs seen at Yale New Haven Hospital, Johns Hopkins Hospital, and St. Michael's Hospital. Up-to-date follow-up information was obtained in all living patients. All patients were severely hypoxic. Neurologic complications (stroke or brain abscess) had occurred in 70% of patients by the time of diagnosis. During the follow-up period (mean, 6 years), three patients died and two others developed new neurologic complications. One of the deaths occurred perioperatively during lung transplantation. All patients underwent transcatheter embolotherapy of any large pulmonary AVMs. A selected group underwent pulmonary flow redistribution, a novel technique. Oxygenation did not improve significantly with embolotherapy of the larger AVMs, but there was a small significant improvement in those patients who underwent pulmonary flow redistribution. The majority (85%) of the living patients are currently working or studying full-time. Patients with diffuse pulmonary AVMs are at increased risk of neurologic complications. Transcatheter embolotherapy does not significantly improve the profound hypoxia, but it may reduce the risk of neurologic complications. Antibiotic prophylaxis is recommended for bacteremic procedures to prevent brain abscess. These patients can live for many years and lead productive lives. We do not recommend lung transplantation because survival with disease is difficult to predict and we have observed a perioperative transplant death.


Analytical results on Muller's ratchet effect in growing populations.
Fontanari introduced [Phys. Rev. Lett. 91, 218101 (2003)] a model for studying Muller's ratchet phenomenon in growing asexual populations. They studied two situations, either including a death probability for each newborn or not, but were able to find analytical (recursive) expressions only in the no-decay case. In this Brief Report a branching process formalism is used to find recurrence equations that generalize the analytical results of the original paper besides confirming the interesting effects their simulations revealed.


Identification of factors associated with virus level in tonsils of pigs experimentally infected with porcine reproductive and respiratory syndrome virus.
Porcine reproductive and respiratory syndrome (PRRS) is one of the most important global swine diseases from both an economic and animal welfare standpoint. PRRS has plagued the US swine industry for over 25 yr, and containment of PRRS virus (PRRSV) has been unsuccessful to date. The primary phase of PRRS, tracked by serum viremia, typically clears between 21 and 42 d postinfection (dpi) but tonsils are a main site of PRRSV persistence and PRRSV can be detected in tonsils in excess of 150 dpi. Measuring tonsil virus (TV) levels at late stages of infection (6 to 7 wk postinfection) can be used to assess tonsil persistence, as levels of virus in tonsil at this time likely influence how long the virus will remain in the tissue. TV levels were measured on pigs experimentally infected with either the NVSL-97-7895 (NVSL; n = 524) or KS-2006-72109 (KS06; n = 328) PRRSV type 2 isolates across five trials. The objectives of this study were to (i) estimate the heritability of TV levels at 35 or 42 dpi; (ii) identify factors the affect TV level, including serum viremia; (iii) identify genomic regions associated with TV level; and (iv) compare results for the two PRRSV isolates. TV level was lowly heritable for both isolates (NVSL: 0.05 ± 0.06; KS06: 0.11 ± 0.10). Level of TV was phenotypically associated with traits related to viral clearance from serum: pigs with low TV levels had an earlier and faster rate of maximal serum viral clearance, lower total serum viral load, and lower viremia level at 35 or 42 dpi. Although no genomic regions with major effects on TV level were identified, several showed some association (>0.1% of total genetic variance in the NVSL-infected dataset, the KS06-infected dataset, and the combined dataset). These regions contained the genes CCL1, CCL2, CCL8, HS3ST3B1, GALNT10, TCF7, C1QA/B/C, HPSE, G0S2, and CD34, which are involved in viral infiltration or replication, immune cell migration, and viral clearance from tissue. Results were similar between the two PRRSV isolates. In conclusion, selection for viral clearance traits in serum may reduce PRRSV persistence in the tonsil across PRRSV isolates. However, genetic correlations need to be estimated to determine whether this will be successful.


A serological investigation of Bovine enterovirus-1, Bovine herpesvirus-1, Bovine viral diarrhea virus, and Parainfluenza-3 infections in camelsin Western Turkey.
Camels (Camelus dromedarius) are bred in Western Turkey, particularly in the province of Aydin, for touristic, social and cultural purposes. Bovine enterovirus‑1 (BEV‑1), Bovine herpesvirus type‑1 (BHV‑1), Bovine viral diarrhea virus (BVDV), and Parainfluenza‑3 (PI‑3) virus infections are significant causes of health and/or economic concerns in several animal species. These agents have not been investigated in the camel population in Turkey. The objective of this study was to serologically investigate the presence and infection rates of these viruses in camels in Aydin province, Western Turkey. Ninety‑two serum samples were taken from clinically healthy camels that were kept in private farms or brought to the local slaughterhouses. Serum neutralization test was performed to assess the presence and the titers of specific antibodies against BEV‑1, BHV‑1, BVDV, and PI‑3 virus in camel sera. Of the 92 camels tested, 30 (32.61%), 2 (2.17%), 54 (58.7%), and 20 (21.74%) were seropositive for BEV‑1, BHV‑1, BVDV, and PI‑3, respectively. These results suggest that, except for BHV‑1, these viral infections are common among camels in Western Turkey. To our knowledge, this the first comprehensive, large‑scale study investigating these viral infections in camels in Turkey.


Management of an Immediate Implant Horizontal Defect Using Freeze-Dried Bone Allograft and a Neodymium:Yttrium-Aluminum-Garnet Laser.
A contemporary protocol for managing horizontal alveolar defects adjacent to immediate implants includes placement of a well-designed provisional restoration to contain graft material and seal the socket. However, immediate provisionalization is not always possible or practical. A 39-year-old male presented with a non-restorable tooth #29, which was extracted. An immediate implant was placed in the tooth #29 position, and a freeze-dried bone allograft was placed in the horizontal defect between the implant platform and osseous walls. A neodymium:yttrium-aluminum-garnet (Nd:YAG) laser was used to create a stable fibrin clot over the graft material. After 31 months, favorable radiographic bone levels and complete papilla fill were noted. The present case illustrates use of an Nd:YAG laser in the management of an immediate implant horizontal defect in lieu of an immediate provisional restoration.


Actinidia chinensis Planch Root extract suppresses the growth and metastasis of hypopharyngeal carcinoma by inhibiting E2F Transcription Factor 1-mediated MNX1 antisense RNA 1.
Increasing evidence has shown that traditional Chinese medicines and their bioactive components exert an anti-tumor effect, representing a novel treatment strategy. Actinidia chinensis Planch Root extracts (acRoots) have been reported to repress cancer cell proliferation and metastasis. The effect of acRoots on hypopharyngeal carcinoma progression was explored in this study. Firstly, data from MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and colony formation assays showed that incubation with accRoots reduced cell proliferation of hypopharyngeal carcinoma cells. Moreover, acRoots promoted the cell apoptosis of hypopharyngeal carcinoma. Secondly, cell migration and invasion of hypopharyngeal carcinoma cells were suppressed by acRoots. Thirdly, E2F1 (E2F Transcription Factor 1) and lncRNA MNX1-AS1 (MNX1 antisense RNA 1) were up-regulated in hypopharyngeal carcinoma tissues, and reduced in hypopharyngeal carcinoma cells post acRoots incubation. Overexpression of E2F1 attenuated acRoots-induced decrease in MNX1-AS1 in hypopharyngeal carcinoma cells. Lastly, administration with acRoots retarded in vivo hypopharyngeal carcinoma growth through down-regulation of E2F1-mediated MNX1-AS1. In conclusion, acRoots exerted tumor-suppressive role in hypopharyngeal carcinoma through inhibition of E2F1-mediated MNX1-AS1.


Alterations of Food-specific Serum IgG4 Titers to Common Food Antigens in Patients With Irritable Bowel Syndrome.
The role of dietary factors in the pathogenesis of irritable bowel syndrome (IBS) is still unclear. The aim of this study was to compare IgG4 levels to common food antigens between patients with IBS and healthy controls. Thirty-two patients diagnosed as IBS according to the Rome III criteria (12 diarrhea subgroup; 20 non-diarrhea subgroup) and 32 sex and age-matched healthy controls participated in the study. Serum IgG4 titers to 90 common foods were measured in each subject. The number of subjects with positivity defined as the cut-off value ≥ 0.7 U/mL was compared. Patients with IBS had significantly higher IgG4 titers to wheat, leek and taro compared to those of controls. Serum IgG4 titers to ginger, cocoa, walnut, white radish, onion, and lettuce in IBS patients tended to be higher than controls. IgG4 titers to wheat, gluten and gliadin in the diarrhea subgroup, and lettuce, leek and taro in the non-diarrhea subgroup tended to be higher compared with controls. The number of subjects with positivity to apple, orange, lettuce, and leek was significantly higher in IBS patients than controls. The number of subjects with positivity to apple, orange, gluten, and gliadin in the diarrhea subgroup, and egg white, pineapple, soybean, lettuce, and leek in the non-diarrhea subgroup was significantly higher compared with controls. Serum IgG4 antibody levels to some common foods are abnormally elevated in IBS patients. The type of foods with abnormally elevated serum IgG4 titers in the diarrhea subgroup may be different from that in the non-diarrhea subgroup.


Tour of a labyrinth: exploring the vertebrate nose.
This special issue of The Anatomical Record is the outcome of a symposium entitled "Inside the Vertebrate Nose: Evolution, Structure and Function." The skeletal framework of the nasal cavity is a complicated structure that often houses sinuses and comprises an internal skeleton of bone or cartilage that can vary greatly in architecture among species. The nose serves multiple functions, including olfaction and respiratory air-conditioning, and its morphology is constrained by evolution, development, and conflicting demands on cranial space, such as enlarged orbits. The nasal cavity of vertebrates has received much more attention in the last decade due to the emergence of nondestructive methods that allow improved visualization of the internal anatomy of the skull, such as high-resolution x-ray computed tomography and magnetic resonance imaging. The 17 articles included here represent a broad range of investigators, from paleontologists to engineers, who approach the nose from different perspectives. Key topics include the evolution and development of the nose, its comparative anatomy and function, and airflow through the nasal cavity of individual species. In addition, this special issue includes review articles on anatomical reduction of the olfactory apparatus in both cetaceans and primates (the vomeronasal system), as well as the molecular biology of olfaction in vertebrates. Together these articles provide an expansive summary of our current understanding of vertebrate nasal anatomy and function. In this introduction, we provide background information and an overview of each of the three primary topics, and place each article within the context of previous research and the major challenges that lie ahead.


Contemporary results of carotid endarterectomy in "normal-risk" patients from the Society for Vascular Surgery Vascular Registry.
Acceptable complication rates after carotid endarterectomy (CEA) are drawn from decades-old data. The recent Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) demonstrated improved stroke and mortality outcomes after CEA compared with carotid artery stenting, with 30-day periprocedural CEA stroke rates of 3.2% and 1.4% for symptomatic (SX) and asymptomatic (ASX) patients, respectively. It is unclear whether these target rates can be attained in "normal-risk" (NR) patients experienced outside of the trial. This study was done to determine the contemporary results of CEA from a broader selection of NR patients. The Society for Vascular Surgery (SVS) Vascular Registry was examined to determine in-hospital and 30-day event rates for NR, SX, and ASX patients undergoing CEA. NR was defined as patients without anatomic or physiologic risk factors as defined by SVS Carotid Practice Guidelines. Raw data and risk-adjusted rates of death, stroke, and myocardial infarction (MI) were compared between the ASX and SX cohorts. There were 3977 patients (1456 SX, 2521 ASX) available for comparison. The SX group consisted of more men (61.7% vs 57.0%; P = .0045) but reflected a lower proportion of white patients (91.3% vs 94.4%; P = .0002), with lower prevalence of coronary artery disease (P < .0001), prior MI (P < .0001), peripheral vascular disease (P = .0017), and hypertension (P = .029), although New York Heart Association grade >3 congestive heart failure was equally present in both groups (P = .30). Baseline stenosis >80% on duplex imaging was less prevalent among SX patients (54.2% vs 67.8%; P < .0001). Perioperative stroke rates were higher for SX patients in the hospital (2.8% vs 0.8%; P < .0001) and at 30 days (3.4% vs 1.0%; P < .0001), which contributed to the higher composite death, stroke, and MI rates in the hospital (3.6% vs 1.8; P = .0003) and at 30 days (4.5% vs 2.2%; P < .0001) observed in SX patients. After risk adjustment, the rate of stroke/death was greater among SX patients in the hospital (odds ratio, 2.05; 95% confidence interval, 1.18-3.58) although not at 30 days (odds ratio, 1.36; 95% confidence interval, 0.85-2.17). No in-hospital or 30-day differences were observed for death or MI by symptom status. The SVS Vascular Registry results for CEA in NR patients are similar by symptom status to those reported for CREST and may serve as a benchmark for comparing results of alternative therapies for treatment of carotid stenosis in NR patients outside of monitored clinical trials. The contemporary perioperative risk of stroke after CEA in NR patients continues to be higher for SX than for ASX patients.


Anxiety and heart rate under psychological stress: The effects of exercise-training.
Abstract The effects of a 12-week exercise-training program on cognitive, somatic, and behavioral anxiety and on heart rate responses to evaluative stress were scrutinized in 89 subjects randomly assigned to an experimental (exercise) or a control group. The training program consisted of exercises that were aimed to the improvement of the general physical fitness (i.e., strength, flexibility, and endurance). Following the 12-week training period, exercising subjects showed improved motor skill capacity as well as higher VO(2) max. In an anxiety inciting test situation, that consisted of the video-taped delivery of a 5-min speech, a mental arithmetic and a fine motor task, exercising subjects showed more favourable responses than control subjects in three ways: (a) they exhibited lower behavioral anxiety during the anticipation phase of the three stressors, (b) they reported lower cognitive and somatic anxiety during the anxiety provoking situation, and (c) their heart rate recovered faster, in contrast to both their baseline heart rate and the control subjects' heart rate, from the stress episode. These results demonstrate that a fitness-oriented exercise program has anxiolytic properties. They also provide a primary evidence that overt behavioral anxiety, as opposed to the usually measured self-reported anxiety, may be affected by exercise.


The metacognitive advantage of deliberative thinkers: a dual-process perspective on overconfidence.
We explored whether the thinking mode--deliberative versus intuitive--that people use to solve a problem or make a judgment influences their awareness of their own and others' performance. The results of 7 studies support the hypothesis that deliberative thinkers have a metacognitive advantage over intuitive thinkers: Deliberative thinkers are aware of both the deliberative solution and the intuitive alternative; realizing that the deliberative solution is better, they are likely to feel more confident and be more accurate in how they assess their performance and that of others. Intuitive thinkers, on the other hand, are aware only of the intuitive solution; whenever this solution is incorrect, they are unaware of how poor their performance was and how they rank in comparison to others. Implications of this metacognitive advantage are discussed.


Comparision of effects of rosuvastatin versus atorvastatin treatment on plasma levels of asymmetric dimethylarginine in patients with hyperlipidemia having coronary artery disease.
Elevated plasma levels of asymmetric dimethylarginine (ADMA) are prevalent in patients with hypercholesterolemia and coronary artery disease. A total of 83 patients with hypercholesterolemia and angiographically documented mild coronary artery stenosis were randomized to rosuvastatin treatment (20 mg) or atorvastatin treatment (40 mg) once daily for 6 weeks after a 4-week dietary lead-in phase. Both statins decreased total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride levels effectively. Only rosuvastatin increased high-density lipoprotein cholesterol (HDL-C) levels. Both rosuvastatin and atorvastatin decreased plasma ADMA levels; rosuvastatin had a significantly greater effect. The reduction in ADMA levels were correlated with the reduction in TC and LDL-C levels as well as LDL-C-HDL-C ratio. Treatment with rosuvastatin or atorvastatin in patients with hyperlipidemia with mild coronary artery stenosis may lead to a decrease in ADMA levels, which may contribute to improved endothelial function.


User fee policies and women's empowerment: a systematic scoping review.
Over the past decade, an increasing number of low- and middle-income countries have reduced or removed user fees for pregnant women and/or children under five as a strategy to achieve universal health coverage. Despite the large number of studies (including meta-analyses and systematic reviews) that have shown this strategy's positive effects impact on health-related indicators, the repercussions on women's empowerment or gender equality has been overlooked in the literature. The aim of this study is to systematically review the evidence on the association between user fee policies in low- and middle-income countries and women's empowerment. A systematic scoping review was conducted. Two reviewers conducted the database search in six health-focused databases (Pubmed, CAB Abstracts, Embase, Medline, Global Health, EBM Reviews) using English key words. The database search was conducted on February 20, 2020, with no publication date limitation. Qualitative analysis of the included articles was conducted using a thematic analysis approach. The material was organized based on the Gender at Work analytical framework. Out of the 206 initial records, nine articles were included in the review. The study settings include three low-income countries (Burkina Faso, Mali, Sierra Leone) and two lower-middle countries (Kenya, India). Four of them examine a direct association between user fee policies and women's empowerment, while the others address this issue indirectly -mostly by examining gender equality or women's decision-making in the context of free healthcare. The evidence suggests that user fee removal contributes to improving women's capability to make health decisions through different mechanisms, but that the impact is limited. In the context of free healthcare, women's healthcare decision-making power remains undermined because of social norms that are prevalent in the household, the community and the healthcare centers. In addition, women continue to endure limited access to and control over resources (mainly education, information and economic resources). User fee removal policies alone are not enough to improve women's healthcare decision-making power. Comprehensive and multi-sectoral approaches are needed to bring sustainable change regarding women's empowerment. A focus on "gender equitable access to healthcare" is needed to reconcile women's empowerment and the efforts to achieve universal health coverage.


Fluctuating asymmetry--indicator of what?
In a population the optimal phenotype is promoted by buffering mechanisms that keep inter- and intra-individual variation low. A link exists between canalization, that controls phenotypic variation, and developmental stability, mostly measured as fluctuating asymmetry of bilateral traits (FA). Both types of variation are associated with the functional importance of a trait, and both are increased by stress of various kinds. But there are also several instances of non-congruence. The concept of developmental stability has been found elusive, and low FA is not the unambiguous measure of well being and good genes that has been claimed. It can be concluded that developmental stability is partly governed by specific, as yet unknown, molecular processes.


Effect of a unique constant-estrogen, pulsed-progestin hormone replacement therapy containing 17beta-estradiol and norgestimate on endometrial histology.
To evaluate the effect of a 17beta-estradiol(E2)/norgestimate (NGM) HRT regimen, which provides constant estrogen in combination with pulsed progestin administration, on endometrial histology in healthy postmenopausal women 40 to 65 years of age who had experienced natural menopause at least 12 months before the start of the study. A total of 1,253 postmenopausal women were randomized to receive either continuous 1 mg E2, or constant estrogen, pulsed progestin regimens of 1 mg E2/30 microg NGM, 1 mg E2/90 microg NGM, or 1 mg E2/180 microg NGM (3 days on, 3 days off) in a 12-month, multicenter, double-blind study. Endometrial biopsies were obtained pre- and post-treatment, and were evaluated by at least 2 (if required, by 3) pathologists who were blinded with respect to treatment and to each other's diagnosis. At the end of the study, no cases of endometrial hyperplasia were diagnosed in subjects who received E2 1 mg/NGM 90 microg or E21 mg/NGM 180 microg, whereas 74 (28%) and 16 (6%) cases of endometrial hyperplasia were diagnosed in subjects who received continuous E2 1 mg and E2 1 mg/NGM 30 microg, respectively. A dose-related endometrial response to NGM was apparent (P < .001). The percentage of patients with inactive/atrophic endometrium increased with NGM dose. The results of this study support the safety and efficacy of this unique HRT regimen and suggest that the minimal NGM dose required to protect the endometrium from hyperplasia in a pulsed progestin regimen consisting of continuous E2 1 mg is 90 microg.


Activation of Matrix Hyaluronan-Mediated CD44 Signaling, Epigenetic Regulation and Chemoresistance in Head and Neck Cancer Stem Cells.
Head and neck squamous cell carcinoma (HNSCC) is a solid tumor composed by a genotypically and phenotypically heterogeneous population of neoplastic cells types. High recurrence rate and regional metastases lead to major morbidity and mortality. Recently, many studies have focused on cellular and molecular mechanisms of tumor progression that can help to predict prognosis and to choose the best therapeutic approach for HNSCC patients. Hyaluronan (HA), an important glycosaminoglycan component of the extracellular matrix (ECM), and its major cell surface receptor, CD44, have been suggested to be important cellular mediators influencing tumor progression and treatment resistance in head and neck cancer. HNSCC contains a small subpopulation of cells that exhibit a hallmark of CD44-expressing cancer stem cell (CSC) properties with self-renewal, multipotency, and a unique potential for tumor initiation. HA has been shown to stimulate a variety of CSC functions including self-renewal, clone formation and differentiation. This review article will present current evidence for the existence of a unique small population of CD44v3highALDHhigh-expressing CSCs in HNSCC. A special focus will be placed on the role of HA/CD44-induced oncogenic signaling and histone methyltransferase, DOT1L activities in regulating histone modifications (via epigenetic changes) and miRNA activation. Many of these events are essential for the CSC properties such as Nanog/Oct4/Sox2 expression, spheroid/clone formation, self-renewal, tumor cell migration/invasion, survival and chemotherapeutic drug resistance in HA-activated head and neck cancer. These newly-discovered HA/CD44-mediated oncogenic signaling pathways delineate unique tumor dynamics with implications for defining the drivers of HNSCC progression processes. Most importantly, the important knowledge obtained from HA/CD44-regulated CSC signaling and functional activation could provide new information regarding the design of novel drug targets to overcome current therapeutic drug resistance which will have significant treatment implications for head and neck cancer patients.


The apoptosome: physiological, developmental, and pathological modes of regulation.
Apoptosis, a form of programmed cell death, is executed by a family of zymogenic proteases known as caspases, which cleave an array of intracellular substrates in the dying cell. Many proapoptotic stimuli trigger cytochrome c release from mitochondria, promoting the formation of a complex between Apaf-1 and caspase-9 in a caspase-activating structure known as the apoptosome. In this review, we describe knockout and knockin studies of apoptosome components, elegant structural and biochemical experiments, and analyses of the apoptosome in various cancers and other disease states, all of which have provided new insight into this critical locus of apoptotic control.


Optical microresonator based on hollow sphere with porous wall for chemical sensing.
A porous-wall hollow glass microsphere (PW-HGM) was investigated as an optical resonator for chemical vapor sensing. A single mode optical fiber taper was used to interrogate the microresonator. Adsorption of chemical molecules into the nanosized pores induced a refractive index change of the thin wall and thus a shift in its resonance spectrum. The PW-HGM resonator had shown higher vapor detection sensitivity in comparison with a solid microsphere under similar test conditions.


Health information technology in the workplace: findings from a 2010 national survey of registered nurses.
The objective of this study was to examine RNs' experiences with health information technology (HIT) and their perceptions of the effect of this technology on quality of care and daily work. The adoption and use of HIT are expected to increase substantially over the next 5 years because of policy efforts at the federal and state levels. Given the size of the RN workforce and their critical role in healthcare delivery, their experiences with HIT could help adoption efforts. The method used was a nationally representative survey of 1500 nurses with a 56% response rate. Findings suggest wide variation in the availability of HIT functionality, with functions more likely available to hospital RNs. Overall, RNs perceived the effect of these technologies on quality of care and their daily work as positive. Ensuring that HIT systems are relevant to and usable for RNs will be a critical component in achieving the meaningful use of these systems.


Role of the ethics committee: helping to address value conflicts or uncertainties.
This article addresses two basic questions about ethics committees: why we have them, and how they might be helpful to clinicians. Our answer to the first question is twofold. First, we suggest that legal, regulatory, and professional forces drove the development of ethics committees, particularly as an alternative to litigation. Second, we argue that ethics committees arose in response to a clinical need for a formal mechanism to address some of the value conflicts and uncertainties that arise in contemporary health-care settings. We argue that this need, reflected in early high-profile legal cases, stems partly from the complex value-laden nature of clinical decision making, a pluralistic societal context, a growing recognition of the rights of individuals to live by their values, and the relevance of those values for medical decision making. In answer to the second question, we draw out three ways ethics committees might be helpful to clinicians: education, policy formation or review, and consultation. We devote the majority of our discussion to ethics consultation and its relation to the emerging area of palliative care. In so doing, we highlight three important differences: (1) the scope or range of cases for which they may be appropriate, (2) focus in any particular case, and (3) general orientation-between ethics consultation and palliative care that clinicians should take into account in deciding to seek the assistance of either or both.


[Peculiarities of clinical and laboratory characteristics of the activity of streptococcal infection in the patients presenting with tonsillar pathology].
The objective of the present study was to characterize peculiar clinical and laboratory features of trivial tonsillitis for the substantiation of the necessity of prescription of antibacterial therapy. A total of 386 patients presenting with various forms of trivial tonsillitis were available for the determination of anti-streptococcal antibody (ASLO, anti-DN-ase B, ASPH) levels. The results of the measurement were compared based on the Centor scale generally used to estimate the necessity of prescribing antibacterial therapy for the treatment of sore throat. It is concluded that laboratory studies of characteristics of S. Рyogenes activity are needed in all the patients presenting with tonsillitis in order to elucidate the etiological factors responsible for pharyngalgia and the necessity of prescription of antibacterial therapy for the prevention of pyogenic systemic complications of streptococcal infection.


Macroautophagy and the oncogene-induced senescence.
The oncogene-induced senescence is emerging as a potent tumor suppressor mechanism and as a possible therapeutic target. Macroautophagy is intimately linked to the senescence condition setup, although its role has not been elucidated yet. Here, we discuss up-to-date concepts of senescence-related macroautophagy and evaluate the current trend of this growing research field, which has relevance in future perspectives toward therapeutic options against cancer.


Vaginally applied diquat intoxication.
We report the case of a woman who introduced 20 mL of diquat concentrate intravaginally. Abdominal pain, vomiting, diarrhea, burning chest pains, and somnolence appeared within the first 24 hours. The vulva and vagina were corrosively inflamed. Acute renal failure appeared on the third day and was treated by 6 hemodialyses over 6 days. The patient was dysarthric with spastic tetraparesis for 3 months. The electroencephalogram, diffusely slow on day 3, was normal on day 28. The electromyoneurogram was normal at all times. Biopsy of a peripheral nerve performed on day 57 following intoxication showed no myelin or axonal alterations.


Mitomycin C application after photorefractive keratectomy in high, moderate, or low myopia: Systematic review and meta-analysis.
Photorefractive keratectomy (PRK) is considered a safe approach laser procedure with a clinical significance in correcting myopia results. PRK requires removing the whole superficial epithelium. The integrity of the epithelial basement membrane and the deposition of abnormal extracellular matrix can put the cornea in a probable situation for corneal haze formation. Mitomycin C (MMC) is applied after excimer laser ablation as a primary modulator for wound healing, limiting corneal haze formation. We aim to summarize the outcomes of MMC application after laser ablation. We searched Scopus, PubMed, Cochrane CENTRAL, and Web of Science till December 2020 using relevant keywords. The data were extracted and pooled as mean difference (MD) or risk ratio (RR) with a 95% confidence interval (CI), using Review Manager software (version 5.4). Our analysis demonstrated a statistically significant result for MMC application over the control group in terms of corneal haze formation postoperatively (RR = 0.29, 95% CI: [0.19, 0.45], P < 0.00001). Regarding corrected distance visual acuity (CDVA), no significant difference was observed between the MMC group and the control group (MD = 0.02; 95% CI: [-0.04, 0.07]; P = 0.56). Regarding the uncorrected distance visual acuity (UDVA), the analysis favored the MMC application with (MD -0.03, 95% CI: [-0.06, -0.00]; P = 0.05). There was no statistically significant increase in complications with MMC. In conclusion, MMC application after PRK is associated with a lower incidence of corneal haze formation with no statistically significant side effects. The long term effect can show improvement regarding UDVA favoring MMC. However, there is no significant effect of MMCs application regarding CDVA, and SE.


Resin-modified glass ionomer cements: fluoride release and uptake.
The aim was to study the short- and long-term fluoride release from resin-modified glass ionomer cements (GIC). The aim was also to determine the effect of fluoride treatment of 9-month-old specimens, consistency of the mix, and pH of the environment on the fluoride release. GIC test specimens were continually exposed to running water, and the fluoride release was measured periodically by storing the specimens in 5 ml deionized water for 1 week and measuring the fluoride content of the solution. After 24 h, 1 month, 9 months, and 11 months in running water four of the six resin-modified GICs released as much as or more fluoride than the auto-curing GIC tested for comparison. Fluoride treatment after 9 months also increased the fluoride release of these four brands, as was the case with the conventional GIC. At 24 h and 1 month two of the resin-modified GICs released smaller amounts of fluoride than the other materials, and the fluoride treatment used on those had no or only a minimal effect. Thin consistency of a mix resulted in higher fluoride release for one resin-modified material than a thick mix. Low pH increased the fluoride release for all materials.


Adenomyosis: new knowledge is generating new treatment strategies.
In the early days, all mucosal invasions of abdominal organs were considered to be one pathological condition of uncertain origin, termed adenomyoma. It was only in the 1920s that endometriosis and adenomyosis were clearly separated and it took approximately 80 years to put forward a new theory reunifying their pathogenesis. Today, identification of adenomyosis is carried out exclusively through vaginal ultrasonography and MRI. These techniques have made a careful evaluation of a distinct anatomical structure and the inner myometrial layers underlying the endometrium, termed the junctional zone, possible. Adenomyosis is characterized by a homogeneous thickening of this portion of the myometrium. When this hyperplasia is associated to an alteration of spiral arterioles' angiogenesis, then both adenomyosis and endometriosis may develop. Evidence is being accumulated that pre-eclampsia, fetal growth restriction and premature delivery may be linked, together representing a new, major obstetrical syndrome characterized by a modified uterine environment around the time of nidation. A dozen different medical or surgical techniques are utilized for the treatment of adenomyosis and novel approaches are being tested. These include use of inhibitors of angiogenesis that have been shown to cause reduced neo-angiogenesis, a significant modification of gene expression and a decrease in the percentage of active lesions. Encouraging results have also been obtained with the levonorgestrel-releasing intrauterine system.


[Long-term therapy in chronic hepatitis C with recombinant alpha interferon].
The dosage and duration of Chronic Hepatitis (CH) C therapy with alpha (alpha-IFN) is still an unresolved problem. Considering mainly antiviral activity of alpha-IFN, the authors carried out research on 35 patients with CH-C to evaluate the efficacy and safety of long term therapy and to compare recombinant alpha-IFN-2a with recombinant alpha-IFN-2b. 21 patients (Group A: 20 males, 1 female, mean age 48.8 years, 14.2% CPH, 76% CAH, 9.5% AC) were treated with r-alpha-IFN-2a; 14 patients (Group B: 7 males, 7 females, mean age 45.2 years, 7.1% CPH, 78.5% CAH, 14.3% AC) were treated with r-alpha-IFN-2b, at a dosage of 3 MU thrice weekly (TIW) for 12 months; the follow-up was from 6 to over 24 months. Complete Response (CR) was achieved in 49.3% of the patients treated, Long Term Response (LTCR) in 19.3%, Partial Response (PR) in 29% and No Response (NR) in 22.6%), Delayed CR in 6.5%. The authors found a similar number of CR and LTRC in group A and group B; a greater percentage of PR in group A and a greater percentage of NR in group B. Early and serious side effects in 4 patients, late and serious side effects in 2 patients were observed. The date suggest that the long term therapy of CH with r-alpha IFN is effective in inducing clinical and biochemical remission in a large portion of patients and a greater number of sustained response, with respect to a therapy schedule of 6 months even at greater dosages.


Peripheral T cell lymphoma in a patient with common variable immunodeficiency disease: case report and literature review.
This report documents the occurrence of a peripheral T cell lymphoma arising in the bone marrow and liver of a patient with common variable immunodeficiency disease. The T cell origin of this lymphoma was demonstrated by immunohistochemical phenotyping and gene rearrangement studies and was not associated with EBV infection of the lymphoma cells. The frequency and characteristics of lymphomas complicating CVID are reviewed.


Epilepsy in Qatar: Causes, treatment, and outcome.
Qatar is a small country on the Eastern coast of the Arabian Peninsula. Its population is a unique mixture of native citizens and immigrants. We aimed to describe the features of epilepsy in Qatar as such information is virtually lacking from the current literature. We summarized information retrospectively collected from 468 patients with epilepsy seen through the national health system adult neurology clinic. Epilepsy was classified as focal in 65.5% of the cases and generalized in 23%. Common causes of epilepsy were as follows: stroke (9%), hippocampal sclerosis (7%), infections (6%), and trauma (6%). Sixty-six percent of patients were receiving a single antiepileptic drug, with levetiracetam being the most frequently prescribed drug (41% of subjects). When the patients were divided by geographical background, remote infections caused the epilepsy in 15% of Asian patients (with neurocysticercosis accounting for 10%) but only in 1% of Qatari and 3% of Middle East/North African subjects (with no reported neurocysticercosis) (p<0.001). Cerebrovascular and neurodegenerative etiologies were the most prominent in Qataris, accounting for 14% (p=0.005) and 4% (p=0.03) of cases, respectively. The choice of antiepileptic drugs varied also according to the regional background, but the seizure freedom rate did not, averaging at 54% on the last clinic visit. To our knowledge, this is the first detailed information about epilepsy in Qatar. The geographical origin of patients adds to the heterogeneity of this disorder. Neurocysticercosis should be in the etiological differential diagnosis of epilepsy in patients coming from Southeast Asian countries, despite the fact that it is not endemic to Qatar. The choice of antiepileptic drugs is influenced by the availability of individual agents in the patients' native countries but had no bearing on the final seizure outcome.


CFD simulation of vertical linear motion mixing in anaerobic digester tanks.
Computational fluid dynamics (CFD) was used to simulate the mixing characteristics of a small circular anaerobic digester tank (diameter 6 m) equipped sequentially with 13 different plunger type vertical linear motion mixers and two different type internal draft-tube mixers. Rates of mixing of step injection of tracers were calculated from which active volume (AV) and hydraulic retention time (HRT) could be calculated. Washout characteristics were compared to analytic formulae to estimate any presence of partial mixing, dead volume, short-circuiting, or piston flow. Active volumes were also estimated based on tank regions that exceeded minimum velocity criteria. The mixers were ranked based on an ad hoc criteria related to the ratio of AV to unit power (UP) or AV/UP. The best plunger mixers were found to behave about the same as the conventional draft-tube mixers of similar UP.