Prostate primary intravascular large B-cell lymphoma: A case report.
Intravascular large B-cell lymphoma (IVLBCL) is a distinct subtype of extranodal diffuse large B-cell lymphoma (DLBCL) and mainly affects elderly population characterized by selective infiltration of neoplastic cells within the lumina of small vessels. Prostate primary IVLBCL is extremely rare. Herein we present a case of a 76-year-old male patient who was admitted with symptoms of severe lower urinary tract obstruction. IVLBCL was diagnosed based on histopathological and immunohistochemical examination of the precious tissue specimens though transurethral prostate resection. Awareness and accurate diagnosis are very important to guide the clinicals in formulation of diagnosis and treatment plan.


Manufacture and characterization of optimized red ginseng drinks containing herbal medicine extracts.
The optimum mixing ratio of red ginseng, herbal medicine extracts, and oligosaccharides for diabetic improvement was investigated and verified through animal experiments. Using the optimum mixing technique, 2% red ginseng extract, 15% oligosaccharides, and 83% herbal medicine extracts were determined to be optimal for red ginseng beverages. The taste was improved as the amount of red ginseng decreased and oligosaccharides increased, whereas antioxidative activity was increased with increased red ginseng. In the animal model in which streptozotocin was administered to BALB-c mice, the red ginseng administration group exhibited lower blood glucose than the diabetic control group, and the blood glucose level was lower in the herbal medicine and red ginseng extract administration group. Insulin concentration was slightly increased by the red ginseng beverage, and hepatotoxicity due to excessive intake of red ginseng beverages was not detected.


Diet and fluid prescription in stone disease.
Dietary factors play an important role in kidney stone formation, and dietary modification can reduce the risk of stone recurrence. Because stone recurrence rates may be as high as 30-50% after 5 years, individualized dietary intervention to prevent stone recurrence should be offered to every patient willing to participate in a diagnostic work-up and to adhere to treatment recommendations. The necessity of prescribing medical therapy to select patients does not obviate the need for an effective dietary and/or fluid prescription. In this review, we summarize specific dietary and fluid recommendations, and emphasize several key concepts. First, risk factors for stone formation vary by age and sex. Second, recommendations should be tailored to the individual patient based on urinary profile and stone type. Third, it is essential that the patient perform follow-up measurements to evaluate the impact of dietary recommendations. Fourth, it is important to distinguish stone passage from new stone formation. If a patient implements dietary changes and then passes a pre-existing stone, this does not mean that the intervention was not effective. Finally, because of the relative paucity of randomized trials, observational studies provide the basis for many clinical recommendations. Adequate fluid intake and appropriate dietary modifications may substantially reduce the morbidity and costs associated with recurrent nephrolithiasis.


Shear modulus reconstruction by ultrasonically measured strain ratio.
In addition to a description of our three previously developed one-dimensional (1D) methods from the viewpoint of shear modulus reconstruction using the strain ratio, two new methods for stabilizing the 1D methods are described, together with their limitations. As confirmed using human in vivo breast tissues, method 1 for evaluating the strain ratio itself is useful when the measurement accuracy of the strain distribution is high. However, because tissues having high shear moduli, such as scirrhous carcinoma, often form singular points/regions, both methods 2 and 3 using the strain ratio (initial estimate) and a regularization method are effective for realizing a unique, stable, useful shear modulus reconstruction. Because method 3 carries out implicit integration only at singular points/regions, whereas method 2 carries out implicit integration throughout the region of interest (ROI), the smaller number of singular points enables more rapid shear modulus reconstruction by method 3 than by method 2. Like method 1, method 3 is also useful when the measurement accuracy of the strain distribution is high. However, when evaluating strain distribution in an ROI with a high spatial resolution to obtain a shear modulus reconstruction having a high spatial resolution, shear modulus reconstructions obtained by methods 1, 2, and 3 often become laterally unstable due to the instability and low accuracy of the strains in the reference regions (reference strains), i.e., regularization in methods 2 and 3 cannot reduce the instability in the initial estimate. To cope with this instability, (i) the reconstruction obtained by calculating the strain ratio should be low-pass filtered; for breast tissues, in particular, the reconstruction of the inverse shear modulus should be low-pass filtered, not the reconstruction of the shear modulus. (ii) Otherwise, when using homogeneous regions as a reference, such as a block of reference material, fatty tissue, or parenchyma, evaluation of the reference strains with a low spatial resolution is effective. Although such evaluation yields a stable reconstruction with a high spatial resolution compared with that obtained by the low-pass filtering of the strain ratio, we confirmed through simulations that, when reducing artifacts due to a 1D reconstruction of the shear modulus, the evaluation yields a low-accuracy reconstruction value of inhomogeneity. In contrast, in such a case the low-pass filtering of the strain ratio yields a more accurate reconstruction value. All the above-mentioned methods using the strain ratio realize real-time shear modulus reconstruction and should be selected appropriately in conventional ultrasonic imaging equipment by considering the application of the reconstruction (i.e., in accordance with the measurement accuracy of the strains and the occurrence of artifacts).


Effects of a CO2-enriched atmosphere on the growth and competitive interaction of a C3 and a C4 grass.
Festuca elatior L., C3, and Sorghum halepense (L.) Persoon, C4, were grown in mixed and unmixed cultures under 350 and 600 ppm CO2 for 112 days. High CO2 levels stimulated increases of total dry weight and leaf surface area in Festuca despite unfavorably high temperatures. In Sorghum, delay of leaf senescence and of floral initiation was attributed to high CO2 concentrations. Growth of unmixed cultures of Sorghum under 600 ppm CO2 was relatively poor because of an apparent interaction of high CO2 with self-shading. All instances of culturexCO2 interactions are offered in supported of the hypothesis that elevated CO2 levels will effect the competitive interaction of C3 and C4 species. Peak net assimilation rates of C3 and C4 plants were seasonally separated at 350 ppm CO2 but coincided at 600 ppm. Based on our observations of Festuca and Sorghum, we project that global CO2 enrichment may alter competitive balance between C3 and C4 plants and subsequently affect seasonal niche separation, species distribution patterns, and net primary production within mixed communities.


Central leptin regulates the UCP1 and ob genes in brown and white adipose tissue via different beta-adrenoceptor subtypes.
The three known subtypes of beta-adrenoreceptors (beta(1)-AR, beta(2)-AR, and beta(3)-AR) are differentially expressed in brown and white adipose tissue and mediate peripheral responses to central modulation of sympathetic outflow by leptin. To assess the relative roles of the beta-AR subtypes in mediating leptin's effects on adipocyte gene expression, mice with a targeted disruption of the beta(3)-adrenoreceptor gene (beta(3)-AR KO) were treated with vehicle or the beta(1)/beta(2)-AR selective antagonist, propranolol (20 microgram/g body weight/day) prior to intracerebroventricular (ICV) injections of leptin (0.1 microgram/g body weight/day). Leptin produced a 3-fold increase in UCP1 mRNA in brown adipose tissue of wild type (FVB/NJ) and beta(3)-AR KO mice. The response was unaltered by propranolol in wild type mice, but was completely blocked by this antagonist in beta(3)-AR KO mice. In contrast, ICV leptin had no effect on leptin mRNA in either epididymal or retroperitoneal white adipose tissue (WAT) from beta(3)-AR KOs. Moreover, propranolol did not block the ability of exogenous leptin to reduce leptin mRNA in either WAT depot site of wild type mice. These results demonstrate that the beta(3)-AR is required for leptin-mediated regulation of ob mRNA expression in WAT, but is interchangeable with the beta(1)/beta(2)-ARs in mediating leptin's effect on UCP1 mRNA expression in brown adipose tissue.


The risk of second cancer (SC) in patients treated for testicular seminoma.
The exact risk of second cancer (S.C.) following treatment of testicular seminoma is not well determined in most series. At our institution, 122 patients with pure seminoma were treated by orchidectomy followed by radiation therapy from 1951 to 1986. Six were lost to follow-up. For the 116 remaining patients, the overall 5-, 10-, 15- and 20-year survival probability was 95%, 90%, 87%, and 84%, respectively. Eleven patients developed 12 second cancers, with a cumulative risk of 7%, 16%, and 16% at 10, 15, and 20 years, respectively. Overall, the risk of second cancer was increased (O/E = 1.97, p = 0.023). There were 3 controlateral seminoma (O/E = 50, p = 0.001), 2 transitional carcinoma of the bladder (O/E = 6.9, p = 0.035), 2 non-Hodgkin's lymphoma (N.S.), 1 acute myeloblastic leukemia, 1 chronic lymphocytic leukemia, 1 intracranial dysgerminoma, 1 rectal and 1 lung adenocarcinoma. Four tumors developed within the previously irradiated field (O/E = 2.2, N.S.). Excluding second seminoma, the overall risk of second cancer was not significant (O/E = 1.33). Five of the 11 patients with second cancer are currently alive without recurrent cancer. We conclude that patients treated for seminoma have an increased risk of second cancer but the overall prognosis remains excellent. The potential factors responsible for second cancer, including irradiation, are discussed.


MPS1 localizes to end-on microtubule-attached kinetochores to promote microtubule release.
In eukaryotes, the spindle assembly checkpoint protects genome stability in mitosis by preventing chromosome segregation until incorrect microtubule-kinetochore attachment geometries have been eliminated and chromosome biorientation has been completed. These error correction and checkpoint processes are linked by the conserved Aurora B and MPS1 Ser/Thr kinases.1,2 MPS1-dependent checkpoint signaling is believed to be initiated by kinetochores without end-on microtubule attachments,3,4 including those generated by Aurora B-mediated error correction. The current model posits that MPS1 competes with microtubules for binding sites at the kinetochore.3,4 MPS1 is thought to first recognize kinetochores not blocked by microtubules and then initiate checkpoint signaling. However, MPS1 is also required for chromosome biorientation and correction of microtubule-kinetochore attachment errors.5,6,7,8,9 This latter function, which must require direct interaction with microtubule-attached kinetochores, is not readily explained within the constraints of the current model. Here, we show that MPS1 transiently localizes to end-on attached kinetochores and that this recruitment depends on the relative activities of Aurora B and its counteracting phosphatase PP2A-B56 rather than microtubule-attachment state per se. MPS1 autophosphorylation also regulates MPS1 kinetochore levels but does not determine the response to microtubule attachment. At end-on attached kinetochores, MPS1 actively promotes microtubule release together with Aurora B. Furthermore, in live cells, MPS1 is detected at attached kinetochores before the removal of microtubules. During chromosome alignment, MPS1, therefore, coordinates both the resolution of incorrect microtubule-kinetochore attachments and the initiation of spindle checkpoint signaling.


Brachycephalic obstructive airway syndrome: much more than a surgical problem.
Brachycephalic obstructive airway syndrome (BOAS) is a chronic, lifelong, debilitating, primarily obstructive airway disease which adversely affects the quality of life of many popular dog breeds. Respiratory restriction in bulldog breeds, pugs and Boston terriers frequently co-exist with pathologies of the gastrointestinal tract. In addition, many brachycephalic dogs that appear clinically normal are, in fact suffering from chronic hypoxia and its systemic consequences. Concurrent gastroesophageal reflux-associated conditions, sleep disorders and systemic hypertension further impact the welfare of affected dogs. Acceptance of BOAS and associated clinical signs as being 'normal for the breed' is common amongst owners. While surgical correction of the upper airway is the mainstay of treatment, the provision of subsequent, frequently lifelong medical management is equally important for the maintenance of an acceptable quality of life, at least for some affected patients. Here we review the current knowledge concerning brachycephaly, combine it with shared clinical experience in the management of this debilitating condition, and discuss ethical considerations and the responsibility of veterinarians to contribute public education and to support appropriate breed standards for animals under our care.


The dappled nature of causes of psychiatric illness: replacing the organic-functional/hardware-software dichotomy with empirically based pluralism.
Our tendency to see the world of psychiatric illness in dichotomous and opposing terms has three major sources: the philosophy of Descartes, the state of neuropathology in late nineteenth century Europe (when disorders were divided into those with and without demonstrable pathology and labeled, respectively, organic and functional), and the influential concept of computer functionalism wherein the computer is viewed as a model for the human mind-brain system (brain=hardware, mind=software). These mutually re-enforcing dichotomies, which have had a pernicious influence on our field, make a clear prediction about how 'difference-makers' (aka causal risk factors) for psychiatric disorders should be distributed in nature. In particular, are psychiatric disorders like our laptops, which when they dysfunction, can be cleanly divided into those with software versus hardware problems? I propose 11 categories of difference-makers for psychiatric illness from molecular genetics through culture and review their distribution in schizophrenia, major depression and alcohol dependence. In no case do these distributions resemble that predicted by the organic-functional/hardware-software dichotomy. Instead, the causes of psychiatric illness are dappled, distributed widely across multiple categories. We should abandon Cartesian and computer-functionalism-based dichotomies as scientifically inadequate and an impediment to our ability to integrate the diverse information about psychiatric illness our research has produced. Empirically based pluralism provides a rigorous but dappled view of the etiology of psychiatric illness. Critically, it is based not on how we wish the world to be but how the difference-makers for psychiatric illness are in fact distributed.


Psychological distress among refugees in Germany: a cross-sectional analysis of individual and contextual risk factors and potential consequences for integration using a nationally representative survey.
Responding to the mental health needs of refugees remains a pressing challenge worldwide. We estimated the prevalence of psychological distress in a large refugee population in Germany and assessed its association with host country factors amenable to policy intervention and integration indicators. A cross-sectional and population-based secondary analysis of the 2017 wave of the IAB-BAMF-SOEP refugee survey. Germany. 2639 adult refugees who arrived in Germany between 2013 and 2016. Psychological distress involving symptoms of depression, anxiety and post-traumatic stress disorder was measured using the Refugee Health Screener-13. Almost half of the population surveyed (41.2% (95% CI: 37.9% to 44.6%)) was affected by mild, moderate or severe levels of psychological distress. 10.9% (8.4% to 13.5%) of the population screened positive for severe distress indicative of an urgent need for care. Prevalence of distress was particularly high for females (53.0% (47.2% to 58.8%)), older refugees (aged ≥55, 70.4% (58.5% to 82.2%)) and Afghans (61.5% (53.5% to 69.5%)). Individuals under threat of deportation were at a greater risk of distress than protection status holder (risk ratio: 1.55 (95% CI: 1.14 to 2.10)), single males at a greater risk than males with nuclear families living in Germany (1.34 (1.04 to 1.74)) and those in refugee housing facilities at a greater risk than those in private housing (1.21 (1.02 to 1.43)). Distressed males had a lower likelihood of employment (0.67 (0.52 to 0.86)) and reduced participation in integration courses (0.90 (0.81 to 0.99)). A trend of reduced participation in educational programmes was observed in affected females (0.42 (0.17 to 1.01)). The finding that a substantial minority of refugees in Germany exhibits symptoms of distress calls for an expansion of mental health services for this population. Service providers and policy-makers should consider the increased prevalence among female, older and Afghan refugees, as well as among single males, residents in housing facilities and those under threat of deportation. The associations between mental health and integration processes such as labour market, educational programme and integration course participation also warrant consideration.


Establishment of Theileria-infected bovine cell lines in scid mice.
Bovine cells transformed by infection with the protozoan parasite Theileria annulata were inoculated subcutaneously or intraperitoneally into C.B.-17 scid mice. Mice injected subcutaneously developed solid tumours at the injection site, whilst those injected intraperitoneally developed ascites. Schizont-infected cells were found in other tissues: infected cells spread much more easily from the intraperitoneal site. Karyotyping of cells isolated from tumours showed no evidence of transfer of parasites to murine cells. These results show that the scid mouse can be used as a host for Theileria-infected bovine cells.


[Color-coded duplex ultrasound findings and transcranial color duplex ultrasound findings in patients with acute inner ear disorders--a preliminary observation].
A prospective investigation of 98 patients with acute loss of inner ear function showed that such patients display changes in the pulsatility of the basilar artery; however, the differences can be appreciated only by comparison with control sonograms during the course of the disease. Patients with sudden deafness or sudden loss of equilibrium generally showed unremarkable findings on duplex sonography of the cervical portions of vessels supplying the brain.


Galectins testing: new promises for the diagnosis and risk stratification of chronic diseases?
Galectins are carbohydrate binding proteins involved in several biological functions such as intracellular signaling, cell to cell interaction and exchanges between cells and the extracellular matrix. Galectins are therefore participating to the control of gene expression, the regulation of immune response and the control of cell growth and viability. Galectins have stimulated in one hand a great interest for their potent contribution to the physiopathology of several diseases and cancers and may represent in another hand relevant biomarkers to support the diagnosis and prognosis of several disorders.


Argon green vs krypton red laser photocoagulation of extrafoveal choroidal neovascular lesions. One-year results in age-related macular degeneration. The Canadian Ophthalmology Study Group.
This multicenter randomized controlled clinical trial performed in Canada was designed to determine whether krypton red laser or argon green laser is superior for treatment of choroidal neovascularization located between 200 and 2500 microns from the center of the foveal avascular zone in patients with age-related macular degeneration. Two hundred ten patients were randomly assigned to treatment with either argon green or krypton red laser, of whom 191 (91%) were determined eligible. Of the eligible patients, 185 (97%) had sufficient follow-up for a comparison of primary-outcome visual acuity at 1 year. We conclude, with 95% confidence, that the krypton red laser is no better than the argon green laser for the treatment of well-defined extrafoveal choroidal neovascularization.


An early work [1910-1913] in Biological Psychology by pioneer psychiatrist, criminologist and philosopher José Ingenieros, M.D. (1877-1925) of Buenos Aires.
One of the earliest recorded works in Biological Psychology was published in 1910 by Argentine psychiatrist José Ingenieros (1877-1925), Professor of Experimental Psychology at the Faculty of Philosophy and Letters of the University of Buenos Aires. Ingenieros, a multifaceted personality and prolific author and educator famous for his lapidary aphorisms, has been considered a 'luminary' for generations. Trained as a physician, he was the first scientist to establish a comprehensive psychological system in Latin America. His long list of publications includes more than 300 titles generally divided in two periods: studies in mental pathology and criminology (1897-1908) and studies in philosophy, psychology and sociology (1908-1925). His works were never made particularly available to English-speaking audiences, despite the fact that certain of his books are still best-sellers in the Spanish-speaking world. We present an overview of Ingenieros' life and work, and a detailed account of his profoundly interesting work Principios de Psicología Biológica, in which he analyzes the development, evolution and social context of mental functions. We also provide an English translation of the Introduction contributed by Nobel laureate Wilhelm Ostwald (1853-1932) to the 1922 German edition of the work, pertinent to the energetic principles Ingenieros used and the study of Psychology as a natural science. It is a hope, 80 years after Ingenieros' parting, to bibliographically resurrect this champion of reason, who, until now, has not been given his due placement in the international psychological and biomedical literature.


Definition of an extracellular matrix protein in rostral portions of the human central nervous system.
We have identified and characterized an extracellular matrix (ECM) glycoprotein of cultured astrocytomas, NEC1, that is expressed in normal human brain parenchyma. Detailed immunohistochemical analysis reveals a region-specific NEC1 pattern along the rostrocaudal axis of the central nervous system (CNS), with strong expression throughout the white matter of telencephalon and diencephalon, scant expression in some areas of mesencephalon, and no expression in pons, cerebellum, medulla, spinal cord, and peripheral nervous system. NEC1 is not co-distributed with any known neural cell type, suggesting that expression of specific ECM proteins in the CNS is segmentally controlled.


[Pharmacokinetics of topically applied fluconazole in the rabbit eye].
To observe the penetration of 0.5% fluconazole (FCZ) into the corneas and aqueous humors of New Zealand white rabbits following its topical application. The rabbit corneas and aqueous humors were obtained and quantified at different times after topically applying 0.5% FCZ to the rabbit eyes. The drug levels were assayed by high performance liquid chromatography (HPLC). The pharmacokinetic parameters were calculated with nonlinear least square method by the computer. FCZ can rapidly penetrate into rabbit corneas. Peak corneal levels occurred essentially immediately at 2 min in the corneas (15.20 +/- 1.95) microgram/g and at 15 min after application in the aqueous (2.39 +/- 0.92 mg/L). The permeability of the corneal epithelial barrier (Kep) was 1.06 x 10(-5). The half-life (t(l/2)) of the cornea was 63.96 min, and that of the aqueous humor was 42.14 min. Topical fluconazole can be used as a topical antifungal agent to treat keratitis and needs further evaluation for treating fungal endophthalmitis.


Increase in PPARγ inhibitory phosphorylation by Fetuin-A through the activation of Ras-MEK-ERK pathway causes insulin resistance.
Obesity induced insulin resistance is primarily regulated by the inhibitory phosphorylation of peroxisome proliferator-activated receptor γ at serine 273 (PPARγS273) which has been shown to be regulated by MEK and ERK. An upstream regulatory molecule of this pathway could be a therapeutic option. Here we analyzed the involvement of Fetuin-A (FetA), a key hepato-adipokine implicated in insulin resistance, as an upstream regulator molecule for the regulation of PPARγ inhibitory phosphorylation. Mice fed with standard diet (SD), high fat diet (HFD) and HFD with FetA knockdown (HFD-FetAKD) were used to examine the role of FetA on PPARγS273 phosphorylation in adipocytes. The mechanism of regulation and its effect on skeletal muscle were studied using primary adipocytes, 3T3-L1 (preadipocyte) and C2C12 (myotube) cell lines. Increased FetA in HFD mice strongly correlated with augmentation of PPARγS273 phosphorylation in inflamed adipocytes while knockdown of FetA suppressed it. This effect of FetA was mediated through the activation of Ras which in turn activated MEK and ERK. On addressing how FetA could stimulate activation of Ras, we found that FetA triggered TNFα in inflamed adipocytes which induced Ras activation. The ensuing sharp fall in adiponectin level attenuated AMPK activation in skeletal muscle cells affecting mitochondrial ATP production. Our data reveal the essential role of FetA induced activation of Ras in regulating PPARγ inhibitory phosphorylation through Ras-MEK-ERK pathway which downregulates adiponectin disrupting skeletal muscle mitochondrial bioenergetics. Thus, FetA mediated PPARγ inactivation has adverse consequences upon adipocyte-myocyte crosstalk leading to disruption of energy homeostasis and loss of insulin sensitivity.


Evaluation of (D-Pro2, D-Trp7,9)-substance P as an antagonist of substance P responses in the rat central nervous system.
The (D-Pro2, D-Trp7,9) analogue of substance P has been tested for substance P antagonist activity in the caudal trigeminal nucleus in vivo, and in the isolated spinal cord in vitro. In neither case was the analogue found to be a specific antagonist of substance P, although the analogue did have weak antagonist actions in the isolated guinea-pig ileum preparation. It is concluded that the analogue is not a suitable tool for the identification of putative substance P systems in the spinal cord or the caudal trigeminal nucleus of the rat.


Mapping glycine uptake and its metabolic conversion to glutathione in mouse mammary tumors using functional mass spectrometry imaging.
Although glutathione plays a key role in cancer cell viability and therapy response there is no clear trend in relating the level of this antioxidant to clinical stage, histological grade, or therapy response in patient tumors. The likely reason is that static levels of glutathione are not a good indicator of how a tissue deals with oxidative stress. A better indicator is the functional capacity of the tissue to maintain glutathione levels in response to this stress. However, there are few methods to assess glutathione metabolic function in tissue. We have developed a novel functional mass spectrometry imaging (fMSI) method that can map the variations in the conversion of glycine to glutathione metabolic activity across tumor tissue sections by tracking the fate of three glycine isotopologues administered in a timed sequence to tumor-bearing anesthetized mice. This fMSI method generates multiple time point kinetic data for substrate uptake and glutathione production from each spatial location in the tissue. As expected, the fMSI data shows glutathione metabolic activity varies across the murine 4T1 mammary tumor. Although glutathione levels are highest at the tumor periphery there are regions of high content but low metabolic activity. The timed infusion method also detects variations in delivery of the glycine isotopologues thereby providing a measure of tissue perfusion, including evidence of intermittent perfusion, that contributes to the observed differences in metabolic activity. We believe this new approach will be an asset to linking molecular content to tissue function.


Liver hydatid cyst leading to bilateral pulmonary artery embolism and bilateral multiple pulmonar echinococcosis via inferior vena cava: report of a case.
Hydatid disease (HD) is a worldwide parasitic disease. Echinococcosis may involve many organs but affect most commonly liver and lungs. The location of echinococcal cysts inside pulmonary artery is extremely rare. Radiologic findings range from purely cystic lesions to a completely solid appearance. Hydatid cysts (HC) can be solitary or multiple and varies size. Pulmonary artery embolism of HC can be symptomatic or asymptomatic. When symptomatic, we see the chest pain, dyspnea, cough, hemoptysis and sometimes acute cor pulmonale or sudden death secondary to massive giant pulmonary artery embolism of HC.


Impact of an acute surgical unit on outcomes in acute cholecystitis.
The acute surgical unit (ASU) model has been associated with improved outcomes for emergency general surgical patients. Few Australasian studies have investigated patients with cholecystitis and none from South Australia. A retrospective cohort study compared patients admitted to our institution with acute cholecystitis during the 2 years before (traditional period) and after (ASU period) introduction of an ASU on 1 August 2012. Primary outcomes were length of stay, rates of definitive surgery on index admission, time to definitive surgery and proportion of cases performed in-hours. Secondary outcomes were time from emergency department referral to admission, time from radiologically confirmed diagnosis to theatre start, rates of conversion to open cholecystectomy, complications and cholelithiasis-related representations while awaiting definitive procedure. A total of 319 patients met the inclusion criteria; 172 and 147 pre- and post-ASU introduction, respectively. Compared with the traditional period, ASU patients had shorter length of stay (3.80 versus 2.83 days, P < 0.0001), higher rates of surgery on index admission (70.9% versus 95.3%, P < 0.0001), shorter time to definitive surgery (28.1 versus 22.1 days, P < 0.001), lower rates of conversion to open cholecystectomy (18.0% versus 7.1%, P = 0.007) and fewer complications (24.4% versus 6.1%, P < 0.0001). Other outcomes were not significantly different. Introduction of an ASU was associated with superior outcomes amongst patients admitted with acute cholecystitis. These findings extend the literature in support of the current model of care.


Happy ageing by trusting our gut microbes.
The human gut microbiota comprises of trillions of micro-organisms in the gut some which secrete metabolites that play a pivotal role in supporting optimal body and organ functions. These dynamic and malleable gut microbes share a bidirectional relationship with their hosts that supports health in an age- and sex-dependent manner. Disruption of the gut microbiota or decrease in their diversity and richness due to unhealthy changes in lifestyle, diet or social disconnection, always results in unwanted outcomes on the host health which fuel chronic disease symptoms including neurodegenerative diseases. Thus, impairment of gut microbiota composition, results in organ decline that accelerates an individual's biological ageing. Here we review evidence supporting the bidirectional relationships between the gut microbiota and biological ageing.


AFLP analysis of genetic relationships among aromatic grapevines (Vitis vinifera).
Genotypic diversity has been detected among aromatic grapevines (Vitis vinifera) by molecular markers (AFLPs). The 22 primer-pairs generated a total of 1,331 bands of which 564 (40%) were polymorphic over all the genotypes. The bootstrap analysis pointed out that a large number of polymorphic bands (200-400) has to be used for a better estimation of the genetic distances among genotypes; 383 polymorphic AFLP bands were used for the cluster and the principal coordinate analyses because they did not present missing data across all the genotypes. The cluster analysis (UPGMA), based on polymorphic AFLP markers, revealed no relationship between the Moscato and Malvasia grapevines. The Malvasias, unlike the Moscatos distinguished by their distinct muscat aroma, have to be considered a more complex group because it includes muscat and non-muscat grapevines. The principal coordinate analysis (PCO) confirmed the pattern of the cluster analysis only for those varieties which presented a low coefficient of dissimilarity, while for the other varieties there was no correspondence between the two analyses. The pattern of aggregation among aromatic grapevines in the cluster and principal coordinate analyses does not support any classification that might include an aromatic grapevine group in V. vinifera. Even though some synonyms and homonyms are present among aromatic grapevines (V. vinifera), genetic diversity exists among genotypes in AFLP markers.


Laparoscopic versus open appendicectomy in Greek reality.
Laparoscopic appendicectomy (LA) may be the treatment of choice for acute appendicitis. Our aim was to assess LA in Greek reality. Within a year, 135 patients with a mean age of 29.25 years (14 to 67) underwent an operation for "acute appendicitis." We analyzed the hospital stay, the morbidity, the cost, and the severity of the inflammation and compared the open appendicectomy [OA (78)] with the LA (57) approach. There were no differences in the appendicitis severity (P = 0.667), and similar complication rate (P = 0.414) and mean hospital stay were observed between the groups (LA = 3.18 vs. OA = 2.97, P = 0.664). In the way, medical procedures are priced in Greece; the mean net cost of LA was 1320.60 euros (1748.05 USD), whereas for OA, it was 237.8 euros (314.77 USD). The severity of appendicitis is not a limitation for LA. Because of an insufficient costing system in Greece, the best cost effectiveness is for young women and obese men.


Thyrotropin receptor gene mutations and TSH resistance: variable expressivity in the heterozygotes.
TSH resistance ranges from overt nonautoimmune hypothyroidism to subclinical hypothyroidism, defined as mild hyperthyrotrophinaemia but a euthyroid state clinically. To date, 23 inactivating mutations of the TSH receptor (TSHR) gene have been proven responsible for the clinical condition, but an absence of mutations in the TSHR gene has been reported for several cases of TSH resistance as well. In this paper, we aimed to investigate the actual role of the TSHR gene in the development of both subclinical and congenital hypothyroidism. 14 hypothyroid newborns, 116 subclinical hypothyroid subjects and 120 healthy controls. Through denaturing high performance liquid chromatography (DHPLC), we screened for mutations the TSHR gene (the proximal promoter, the exons and their flanking regions), and evaluated the association between serum TSH and functionally characterized alleles identified. In the hypothyroid patients, one patient was heterozygous for a new missense variation, E34K, whereas two others patients were either homozygous or heterozygous for the P162A substitution. In the subclinical hypothyroid subjects, we detected only heterozygous substitutions: they are mostly new (123-124insTGCA, P27T, R46P, 555-561delTATTCTT, D403N, W488R, M527T), while six correspond to already published mutations (P162A, R109Q, L252P and three C41S). We only focused on those mutations that had been functionally characterized in vitro, and in whom serum TSH was available from family members. A single grossly mutated allele (such as C41S or 555-561del) invariably leads to a condition of subclinical hypothyroidism, whereas in case of heterozygous carriers of mutations partially affecting the receptor function (such as P162A or L252P), a remarkable variable expressivity was detected among individuals belonging to different generations.


Dopamine modulating agents alter individual subdomains of motivation-related behavior assessed by touchscreen procedures.
Development of novel treatments for motivational deficits experienced by individuals with schizophrenia and major depressive disorder requires procedures that reliably assess effort-related behavior in pre-clinical models. High-throughput touchscreen-based testing, that parallels the computerized assessment of human patients, offers a platform for the establishment of tasks with high level of translational validity. Considerable efforts have been made to validate the touchscreen version of tasks that measure the degree of effort an animal is willing to invest for a reward, such as progressive ratio task. While motivational studies primarily focus on reporting alterations of a breakpoint, touchscreen assessment allows to collect multiple measures, especially if additional tasks would be adapted to the touchscreen environment. Classifying these measures to distinct behavioral subdomains is necessary for an evaluation of pre-clinical models. Here we apply data-driven classification techniques to identify behavioral clusters from dataset obtained in progressive ratio task and a novel effort-related choice task that we established and validated in the touchscreen boxes. Moreover, we measure the effect of pharmacological manipulations of the level of dopamine, a key regulator of reward- and effort-related processing, on individual behavioral subdomains that describe effort-related activity, non-specific activity, locomotion, and effort-related choice. Our approach expands the touchscreen-based assessment of pre-clinical models of motivational symptoms, identifies the most relevant behavioral measures in assessing the degree of reward-driven effort and contributes to the understanding of the role of dopamine in mediating distinct aspects of effort-related motivation.


Longitudinal Transcriptomic Profiling in Carrageenan-Induced Rat Hind Paw Peripheral Inflammation and Hyperalgesia Reveals Progressive Recruitment of Innate Immune System Components.
Pain is a common but potentially debilitating symptom, often requiring complex management strategies. To understand the molecular dynamics of peripheral inflammation and nociceptive pain, we investigated longitudinal changes in behavior, tissue structure, and transcriptomic profiles in the rat carrageenan-induced peripheral inflammation model. Sequential changes in the number of differentially expressed genes are consistent with temporal recruitment of key leukocyte populations, mainly neutrophils and macrophages with each wave being preceded by upregulation of the cell-specific chemoattractants, Cxcl1 and Cxcl2, and Ccl2 and Ccl7, respectively. We defined 12 temporal gene clusters based on expression pattern. Within the patterns we extracted genes comprising the inflammatory secretome and others related to nociceptive tissue remodeling and to sensory perception of pain. Structural tissue changes, involving upregulation of multiple collagens occurred as soon as 1-hour postinjection, consistent with inflammatory tissue remodeling. Inflammatory expression profiling revealed a broad-spectrum, temporally orchestrated molecular and cellular recruitment process. The results provide numerous potential targets for modulation of pain and inflammation. PERSPECTIVE: This study investigates the highly orchestrated biological response during tissue inflammation with precise assessment of molecular dynamics at the transcriptional level. The results identify transcriptional changes that define an evolving inflammatory state in rats. This study provides foundational data for identifying markers of, and potential treatments for, inflammation and pain in patients.


Factors associated with dynamic knee valgus angle during single-leg forward landing in patients after anterior cruciate ligament reconstruction.
A few studies have reported on how to predict increased dynamic knee valgus angle (KVA), a risk factor for second anterior cruciate ligament (ACL) injury after ACL reconstruction. This study aimed to identify the factors with the potential to predict the KVA during single-leg hop landing. Using three-dimensional motion analysis systems, knee motion during a single-leg hop landing task was measured in 22 patients who had undergone ACL reconstruction at 8-10 months postoperatively. The KVA at initial contact (IC) and maximum KVA during the 40-ms period after IC were calculated using the point cluster technique; correlations between the KVA and other factors were assessed. We performed multiple regression analysis to determine whether KVA could be predicted by these parameters. The KVA was significantly negatively correlated with the static femorotibial angle (FTA; P < 0.01) and patient height (P < 0.01). It was positively correlated with the body mass index (P < 0.05). Multiple regression analysis showed that a small FTA could predict the KVA at IC (β: 0.52, 95% confidence interval (CI): 2.24-(-0.42); P < 0.01). The maximum KVA during the 40-ms period after IC was associated with the FTA (β: 0.46, 95% CI: 2.22-(-0.26); P = 0.02) and height (β: 0.40, 95% CI: 0.59-(-0.02); P = 0.04). At 8-10 months after ACL reconstruction, the KVA was significantly correlated with the FTA, with reduced FTA being associated with an increased dynamic KVA during single-leg hop landing. The measurement of anatomical parameters may aid in predicting the second ACL injury risk after reconstruction.


Localization, characterization and function of pituitary adenylate cyclase-activating polypeptide during brain development.
Neural development is controlled by region-specific factors that regulate cell proliferation, migration and differentiation. Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that exerts a wide range of effects on different cell types in the brain as early as the fetal stage. Here we review current knowledge concerning several aspects of PACAP expression in embryonic and neonatal neural tissue: (i) the distribution of PACAP and PACAP receptors mRNA in the developing brain; (ii) the characteristic generation of neurons, astrocytes and oligodendrocytes in brain areas where the PACAP receptor is expressed and (iii) the role of PACAP as a regulator of neural development, inducing differentiation and proliferation in association with other trophic factors or signal transduction molecules.


Bilateral knee septic arthritis: Was it from sternal wound?
Polyarticular septic arthritis is a rare but life-threatening condition and should not be underestimated. Clinicians should look for potential source of infection, either local spread or hematogenous distribution. However, this should not delay the main treatment for septic arthritis.


Responding to a significant recruitment challenge within three nationwide psychoeducational trials for cancer patients.
When faced with a significant recruitment challenge for three nationwide psychoeducational trials targeting prostate and breast cancer patients, the Cancer Information Service Research Consortium initiated outreach efforts to increase accrual. Recruitment is reported by major outreach strategy to inform the use of similar campaigns, either as primary recruitment efforts or to supplement "in-reach" recruitment within oncology settings. During a 33-month period, recruitment was tracked from the National Cancer Institute's Cancer Information Service (CIS), the American Cancer Society (ACS), Dr. Susan Love Research Foundation's Love/Avon Army of Women (AOW), Internet advertising, press releases, radio/television interviews, recruitment materials in community venues, and outreach to churches and cancer support organizations. Across projects, the majority (89 %) of recruited participants (N = 2,134) was obtained from the CIS (n = 901, 19 months of recruitment), AOW (n = 869, 18 months), and ACS (n = 123, 12 months). Other efforts showed minimal gain in recruitment. Cancer information programs (e.g., CIS and ACS) and registries of individuals willing to participate in cancer-related research (e.g., AOW) can represent exceptional resources for outreach recruitment of cancer patients, especially when the eligibility criteria are highly restrictive. However, these resources do not yield samples representative of the larger population of adults diagnosed with cancer, and conclusions from such trials must be tempered accordingly. Inadequate recruitment to randomized controlled trials limits the creation of useful interventions for cancer survivors. By enrolling in cancer registries and taking part in research, cancer survivors can contribute to the development of effective resources for the survivor population.


Changing Primary Care and Growing Nurse Practitioner Workforce: Key Policy and Organizational Issues: An Interview With Dr Lusine Poghosyan.
In this column, nurse scientist Lusine Poghosyan, PhD, MPH, RN, FAAN, is interviewed. Dr Poghosyan has focused her research on advancing the role of nurse practitioners in primary care.


Energy requirements of Adélie penguin (Pygoscelis adeliae) chicks.
The energy requirements of Adélie penguin (Pygoscelis adeliae) chicks were analysed with respect to body mass (W, 0.145-3.35 kg, n = 36) and various forms of activity (lying, standing, minor activity, locomotion, walking on a treadmill). Direct respirometry was used to measure O2 consumption (VO2, l.h-1) and CO2 production. Heart rate (HR, bpm) was recorded from the ECG obtained by both externally attached electrodes and implantable HR-transmitters. The parameters measured were not affected by hand-rearing of the chicks or by implanting transmitters. HR measured in the laboratory and in the field were comparable. Oxygen uptake ranged from VO2 = 1.50.W0.921 in lying chicks to VO2 = 2.25.W1.024 at maximal activity, RQ = 0.76. Metabolic rate in small wild chicks (0.14-0.38 kg) was not affected by time of day, nor was their feeding frequency in the colony (Dec 20-21). Regressions of HR on VO2 were highly significant (p less than 0.0001) in transmitter implanted chicks (n = 4), and two relationships are proposed for the pooled data, one for minor activities (VO2 = -7.23 + 1.82.W + 0.03 HR), and one for walking (VO2 = -11.89 + 1.117.W + 0.058.HR). Oxygen consumption, mass of the chick (2-3 kg), and duration of walking (T, s) were related as VO2 = -0.746 + 1.87.W + 0.076.T, whereas mass-specific O2 consumption was related to walking speed (S, m.s-1) as VO2.W-1 = 1.60 + 7.39.S.


Moderate exercise changes synaptic and cytoskeletal proteins in motor regions of the rat brain.
Physical exercise is known to enhance brain function in several aspects. We evaluated the acute effects of a moderate forced exercise protocol on synaptic proteins, namely synapsin I (SYN) and synaptophysin (SYP), and structural proteins (neurofilaments, NFs) in rat brain regions related to motor function and often affected by neurodegenerative disorders. Immunohistochemistry, Western blotting and real-time PCR were used to analyze the expression of those proteins after 3, 7 and 15days of exercise (EX3, EX7 and EX15). In the cerebellum, increase of SYN was observed at EX7 and EX15 and of NF68 at EX3. In the substantia nigra, increases of protein levels were observed for NF68 and NF160 at EX3. In the striatum, there was an increase of SYN at EX3 and EX7, of SYP at EX7 and of NF68 at EX3. In the cortex, decreased levels of NF68 and NF160 were observed at EX3, followed by an increase of NF68 at EX15. In the reticular formation, all NF proteins were increased at EX15. The mRNA data for each time-point and region also revealed significant exercise-related changes of SYN, SYP and NF expression. These results suggest that moderate physical exercise modulates synaptic and structural proteins in motor brain areas, which may play an important role in the exercise-dependent brain plasticity.


Practical considerations for reducing mortality rates in alloxan-induced diabetic rabbits.
Chemically-induced diabetic animal models have been employed in many areas of diabetes mellitus (DM) research, but managing post-induction animal survival rates remains one of the main downsides. The aim of the present study was to propose a reliable approach to animal management and monitoring after DM induction in a rabbit model in order to reduce animal mortality rates. DM was induced by injecting alloxan in 12 New Zealand White rabbits. A preventive subcutaneous glucose administration to counteract a potentially lethal hypoglycemic phase following alloxan injection was performed on individual bases. Blood glucose level (BGL) was checked hourly for the first 36 h, then every 2 h until the hyperglycemic state was confirmed. All 12 rabbits survived a 48-hour post-induction phase. The critical hypoglycemic phase's start points and duration differed significantly among the rabbits, lasting from 6.7 to 37 h (19.75 ± 8.44). The rabbits entered the final hyperglycemic phase 18 h at the earliest and 42 h at the latest after induction (26.63 ± 7.07). The average daily BGLs throughout the study period ranged from 268 to 512 mg/dL (413.73 ± 76.69). Eleven rabbits survived until the end of the experiment. The variability of rabbits' responses to alloxan injection emphasizes the importance of monitoring rabbit behavior and thoroughly checking BGLs, followed by a preventive glucose administration based on rabbits' individual needs for up to 36 h after alloxan injection. The proposed approach seems to reduce animal mortality.


The effect of an unsuccessful subthreshold shock on the energy requirement for the subsequent defibrillation.
The effect of an unsuccessful subthreshold shock on the energy requirement for the subsequent defibrillation was studied in 10 anesthetized dogs. Defibrillation was achieved with a spring catheter electrode in the superior vena cava and a patch electrode on the anteroapical ventricular wall. Success rates of defibrillation 20 seconds from the onset of ventricular fibrillation were determined at three energy levels with and without a preceding subthreshold shock. Altogether, 637 episodes of fibrillation-defibrillation were performed (63.7 +/- 6.7 per dog). Predicted energy levels for defibrillation success rates of 50% and 80% (E50 and E80) acquired from a logistic regression curve were 0.0303 +/- 0.0064 and 0.0367 +/- 0.0069 joule/gm, respectively, without subthreshold shocks. E50 and E80 with an unsuccessful subthreshold shock resulted in comparable values (E50: 0.0325 +/- 0.0041 joule/gm; E80: 0.0.380 +/- 0.0100 joule/gm). Our results suggest that an unsuccessful low-energy shock does not alter the energy requirement for subsequent defibrillation with an implantable defibrillator.


Organic and inorganic fouling at quartz-liquid interface in ultraviolet photoreactors during on-line sterilization of cheese whey.
This article reports on lamp fouling during on-line ultraviolet (UV) sterilization of cheese whey. The extent of fouling as well as the composition of fouling materials was studied after the operation of three tubular UV reactors of different flow thicknesses (18, 13, and 6 mm) for 48 h at a 2-h residence time. Lamp fouling, which significantly affected the sterilization efficiency, was realized after an extended period of operation. The extent of lamp fouling increased with a decrease in the thickness of the flowing cheese whey (14.42, 15.31, and 25.25 g for 18-, 13-, and 6-mm thickness, respectively). A strong relationship between the extent of fouling and the steady-state outlet temperature was observed. The fouling material contained 63.51 to 77.19% protein, 12.57 to 16.49% fat, and 6.51 to 9.47% minerals on dry weight bases compared with 1% protein, 0.5% fat, and 0.4% minerals in raw cheese whey. The organic and inorganic material concentrations in the fouling material increased with a decrease in the flow thickness. The fouling mechanism was owing to adsorption and direct ion exchange, which were enhanced by the high temperature and low pH attained in the study. Improved designs of UV reactors in which the contact between the flowing material and the quartz surface should be developed.


Data for cardiovascular modeling.
Data are required for a meaningful approach to quality and cost-conscious cardiovascular care. How to identify the types of data available and their sources, advantages and limitations to their use, issues involved in combining data from different sources for decision modeling and some possible solutions are discussed in this summary of the Working Group on Data for Cardiovascular Modeling.


High expression of luteinizing hormone receptors messenger RNA by human cumulus granulosa cells is in correlation with decreased fertilization.
To elucidate the LH receptor (LHR) expression patterns in human granulosa cells (GCs) from antral to preovulatory stages, and to investigate a correlation to oocyte function. Luteinized preovulatory GCs were obtained from preovulatory follicles aspirated during IVF (≥ 17 mm). The GCs from small- (<10 mm) and medium-sized (10-15 mm) follicles were obtained during in vitro maturation (IVM) procedures. Cumulus GCs were obtained during oocyte denudation for intracytoplasmatic sperm injection (ICSI) procedures (IVF). Referral center. Seventy IVF patients and 20 IVM patients. GC collection. The LHR expression levels in mural and cumulus GCs of different follicular sizes and their correlation to oocyte outcome. The LHR expression increased with follicle size and was higher in mural GCs compared with cumulus cells. The LHR expression in cumulus GCs from preovulatory follicles was higher in metaphase II (MII) oocytes than in metaphase I or germinal vesicle oocytes (IVF). Unexpectedly, higher expression of LHR in cumulus GCs of MII oocytes correlated with decreased fertilization rates. The LHR expression in small follicles obtained in IVM suggests a role for hCG administration during IVM procedures. Overexpression of LHR in cumulus GCs of MII oocytes may signal malfunction of oocytes and low fertilization capacity.


Establishment and comprehensive analysis of a new human transformed follicular lymphoma B cell line, Tat-1.
A spontaneously EBV transformed follicular lymphoma (FL) cell line, Tat-1, was established from the lymph node biopsy specimen of a patient with B cell FL, grade 1 in transformation to high grade disease. Tat-1 cells expressed lymphoid markers and developed tumor masses in immunodeficient mice. Bcl-2, Bcl-X(L), Bax and p53 protein expression was revealed by Western blotting. Flow cytometric analysis confirmed P-gp expression. Cytogenetically, the Tat-1 cell line showed identical chromosomal alterations to that of the initial biopsy specimen, among which the most notable were the t(14;18) typical of FL and additional abnormalities involving chromosomes 1, 8 and 13. Multicolor FISH analysis delineated all abnormalities, including a t(1p;8q), a der(8)(8q24::14q32::18q21) and a der(13)(13q32::8q24::14q32::18q21). Further FISH investigations using a locus-specific probe cocktail containing c-myc, IgH and bcl-2 revealed fusion of these three loci on the derivatives 8 and 13, in addition to the derivative 14 IgH/bcl-2 fusion and an extra copy of c-myc on derivative chromosome 1. These results demonstrate an additional example of the deregulation of bcl-2 and c-myc expression through recombination with a single IgH enhancer region. The unusual molecular features of the Tat-1 cell line render it a unique tool for studies focused on cytogenetic alterations, expression of multidrug resistance phenotype and expression of anti-apoptotic proteins in FL.


The Gluteus Medius Experiences Significant Excursion With Hip Flexion.
To evaluate the effect of hip flexion and rotation on excursion of the gluteus medius (Gmed) and minimus (Gmin) myotendinous unit. Seven hips from 4 cadaveric specimens (males, 68.5 ± 18.3 years old) were dissected to isolate the Gmed posterior and lateral insertions and the Gmin proximal and distal insertions. Sutures were placed from tendon insertions through origins created in the iliac fossa to simulate the myotendinous unit. A load of 10N was applied. Myotendinous excursion was measured at 10° hip extension and 0°, 45°, and 90° of hip flexion in neutral rotation, and from maximum internal and external rotation in 90° flexion. The amount of abduction and rotation was also measured at each flexion position with 20N applied to each tendon. Repeated-measures analysis of variance with Tukey post hoc was used for statistics. Gmed-lateral excursion ranged from 2.4 ± 0.4 mm in 10° of hip extension to 23.0 ± 1.5 mm in 90° of flexion (P < .001), and Gmed-posterior excursion ranged from 0.92 ± 0.5 mm in 10° of extension to 38.1 ± 1.1 mm in 90° of flexion (P < .001). Gmin excursion shortened with hip flexion from 4.2 ± 0.3 mm in 10° of extension to -0.2 ± 1.5 mm in 90° of flexion (Gmin-prox: P = .525, Gmin-distal: P < .001). At 90° flexion from maximum internal to maximum external rotation, Gmin-distal and proximal demonstrated a 92.6% and 51.3% increase in excursion, respectively (P < .001). Gmed-lateral and Gmed-posterior demonstrated 49.4% and 23.1% increase in excursion with external rotation, respectively (P < .001). The Gmed myotendinous unit undergoes significant excursion with hip flexion, whereas both Gmed and Gmin had significant excursion with femoral external rotation in 90° flexion. It is important to understand whether active or passive hip flexion or rotation in the early postoperative period causes excessive strain to an abductor tendon repair. We found that consideration should be given to limit flexion after Gmed repair and external rotation after Gmed or Gmin repairs.


Overexpression of tumor suppressor TSLC1 by a survivin-regulated oncolytic adenovirus significantly inhibits hepatocellular carcinoma growth.
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Oncolytic viruses represent a promising therapeutic agent or vehicle to human cancers due to their ability of selectively lysing cancer cells but not in normal cells. TSLC1, a novel tumor suppressor gene, was loss in many human cancers including HCC, not in normal cells. The current study is focused on the antitumor effect of TSLC1-armed survivin-regulated oncolytic adenovirus for HCC and to explore their molecular mechanism. The expression of tumor suppressor TSLC1 and survivin was detected by quantitative PCR. The recombinant virus Ad.SP-E1A-E1B((Δ55))-TSLC1 (brief name as SD55-TSLC1) was constructed by inserting TSLC1 gene into the dual-regulated oncolytic adenovirus vector Ad.SP-E1A-E1B((Δ55)). Then, we performed the antitumor experiments of SD55-TSLC1 in vitro and in nude mice xenografted with Huh7 liver cancer. The expression of TSLC1 was lower in HCC cells than in normal cells, which implied TSLC1 is a tumor suppressor of liver cancer. Survivin expression is higher in detected HCC cells than in normal cells. The SD55-TSLC1 exhibited an excellent antitumor effect on HCC cell growth in vitro but does no or little damage to normal liver cells. Animal experiment further confirmed that SD55-TSLC1 achieved significant inhibition of Huh7 liver cancer xenografted growth. Furthermore, the mechanism of antitumor efficacy by SD55-TSLC1 was elucidated to be due to the activation of caspase apoptotic pathway including the inducement of caspase-3, caspase-8, and poly (ADP-ribose) polymerase cleavage. This is the first report of TSLC1 by oncolytic adenovirus with an excellent antitumor effect to liver cancer growth. These data suggest that an oncolytic adenovirus expressing TSLC1 is effective and support that SD55-TSLC1 may be a potent antitumoral agent for future clinical trials of liver cancer.


Characterization and determination of casein glycomacropeptide in dairy products by UHPLC-MS/MS based on its characteristic peptide.
The ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS) method was built to quantify the casein glycomacropeptide (CGMP) in bovine dairy products accurately based on targeted proteomics. Qualitative analysis of theoretical peptides was carried out using high-resolution mass spectrometry (HRMS) and protein software. Isotope-labeled characteristic peptides were acquired via the labeled amino acid condensation method to correct the matrix effects. Peptide MAIPPK was the representative characteristic peptide for distinguishing the CGMP from κ-casein through trypsin digestion. After optimizing the pre-treatment conditions, the final 8% oxidant concentration was selected and the 10% formic acid concentration with 2.5 h oxidation time. Moreover, the results of methodological verification showed that the recovery rate was 103.7%, meanwhile the precision of inter-day and intra-day was less than 5%. In conclusion, the research demonstrated the characteristic peptide MAIPPK could quantitatively applied to detect CGMP in dairy products.


Electrical Oscillations in Two-Dimensional Microtubular Structures.
Microtubules (MTs) are unique components of the cytoskeleton formed by hollow cylindrical structures of αβ tubulin dimeric units. The structural wall of the MT is interspersed by nanopores formed by the lateral arrangement of its subunits. MTs are also highly charged polar polyelectrolytes, capable of amplifying electrical signals. The actual nature of these electrodynamic capabilities remains largely unknown. Herein we applied the patch clamp technique to two-dimensional MT sheets, to characterize their electrical properties. Voltage-clamped MT sheets generated cation-selective oscillatory electrical currents whose magnitude depended on both the holding potential, and ionic strength and composition. The oscillations progressed through various modes including single and double periodic regimes and more complex behaviours, being prominent a fundamental frequency at 29 Hz. In physiological K(+) (140 mM), oscillations represented in average a 640% change in conductance that was also affected by the prevalent anion. Current injection induced voltage oscillations, thus showing excitability akin with action potentials. The electrical oscillations were entirely blocked by taxol, with pseudo Michaelis-Menten kinetics and a KD of ~1.29 μM. The findings suggest a functional role of the nanopores in the MT wall on the genesis of electrical oscillations that offer new insights into the nonlinear behaviour of the cytoskeleton.


Comparative study on the antioxidant activities of the different extracts and the composition of the oil extracted by n-hexane from Iranian Vitex pseudo-negundo.
Antioxidant activities of different extracts obtained from the aerial parts of Vitex pseudo-negundo from Kashan, central Iran, were evaluated for the first time in this study using β-carotene/linoleic acid and scavenging of free-radical (DPPH) assays. Water extract showed the highest activity in both assays. GC-MS analysis of the oil extracted by n-hexane revealed 46 compounds with trans-β-farnesene being the main component. Several new compounds, not reported in the previous literature, were identified in the essential oil of this chemo-type.


Anatomical basis of pelvic growth in bladder exstrophy.
Pelvic growth in bladder exstrophy was studied in 10 patients. Growth of their pelves in length as well as in width was similar to that found by Tanner. Meanwhile, the speed at which the diastasis of the pubic symphysis increases is variable. Before 5 years of age and during the end of growth it is fast, whereas it is slow between 5 and 10 years of age. There are no radiological abnormalities of hip joint orientation, and the acetabular angles are normal.


Acute Hyperglycemia Does Not Affect Brain Swelling or Infarction Volume After Middle Cerebral Artery Occlusion in Rats.
Stroke disproportionally affects diabetic and hyperglycemic patients with increased incidence and is associated with higher morbidity and mortality due to brain swelling. In this study, the intraluminal suture middle cerebral artery occlusion (MCAO) model was used to examine the effects of blood glucose on brain swelling and infarct volume in acutely hyperglycemic rats and normo-glycemic controls. Fifty-four rats were distributed into normo-glycemic sham surgery, hyperglycemic sham surgery, normo-glycemic MCAO, and hyperglycemic MCAO. To induce hyperglycemia, 15 min before MCAO surgery, animals were injected with 50 % dextrose. Animals were subjected to 90 min of MCAO and sacrificed 24 h after reperfusion for hemispheric brain swelling and infarct volume calculations using standard equations. While normo-glycemic and hyperglycemic animals after MCAO presented with significantly higher brain swelling and larger infarcts than their respective controls, no statistical difference was observed for either brain swelling or infarct volume between normo-glycemic shams and hyperglycemic shams or normo-glycemic MCAO animals and hyperglycemic MCAO animals. The findings of this study suggest that blood glucose does not have any significant effect on hemispheric brain swelling or infarct volume after MCAO in rats.


Direct capture of product from fermentation broth using a cell-repelling ion exchanger.
A new technique for treating anion exchangers has been proposed allowing direct capture of the fermentation product, shikimic acid directly from the cell-containing fermentation broth. A layer of hydrophilic polymer, poly(acrylic acid) (PAA) has been physically adsorbed on the anion exchanger followed by a covalent cross-linking of PAA. The PAA layer is penetrable for small molecules despite being negatively charged as PAA is, but the polymer layer repels large negatively charged structures like cell debris and cells preventing them from adsorption to the chromatographic matrix. The binding capacity for pure shikimic was about 81 mg/ml adsorbent for both cross-linked PAA-Amberlite and native Amberlite in the fluidized mode of column operation. Binding capacity dropped to 17 and 15 mg per ml adsorbent, respectively, when using filtrated fermentation broth and to about 10 mg/ml adsorbent for cross-linked PAA-Amberlite when using directly the fermentation broth containing cells. Native Amberlite cannot be used for the direct capture of shikimic acid due to the immediate clogging of the column and the collapse of the expanded bed. The cross-linked PAA-Amberlite was used repeatedly for the direct adsorption of shikimic acid from the industrial fermentation broth.


Clinical outcomes of vanishing twin syndrome and selective fetal reduction after double embryos transferred in IVF pregnancy: A propensity score matching study.
The purpose of this study was to analyze the influence of early vanishing twin syndrome (VTS) and selective fetal reduction (SEFR) on surviving singleton births in in-vitro fertilization (IVF) pregnancy. We collected patients who conceived through IVF and delivered singletons over the past six years. The VT group (n = 194) and SEFR group (n = 144) had underwent double embryos transferred (DET) and only one fetus was born, due to the subsequent one birth reduction. The SET group had one embryo transferred (SET) and gave birth to singleton. Using the propensity score matching (PSM) method to reduce confounding, the VT group and SEFR group were matched and compared with 570 and 576 singleton controls, respectively (SET-I/II group). Obstetric complications and neonatal outcomes were compared. In addition, quantity and quality of transferred embryos of VT (n = 194) and singleton groups (born with singleton after DET and matched with VT group by PSM, n = 554) were compared. Compared with the SET-I group, VT group had increased incidence of severe obstetric complications, including severe preeclampsia (p = 0.031), oligohydramnios (p = 0.038) and polyhydramnios (p = 0.015). VT group was more likely to show more frequent small for gestational age (SGA) (p = 0.046) and very small for gestational age (VSGA) (p = 0.031). Newborns in the SEFR group had a significantly lower birth weight (p = 0.005) and were more likely to manifest as low birthweight (LBW) (p = 0.009) and very low birthweight (VLBW, birth weight < 1500 g) (p = 0.012), and the incidence of very large for gestational age (VLGA) was lower (p = 0.030), compared with the control group. There were more developmental abnormalities in newborns of VTS, for decreased incidence of SGA (OR 0.156, 95% CI 0.036-0.669), VSGA (OR 0.057, 95% CI 0.006-0.553) and VLGA (OR 0.415, 95% CI 0.212-0.815) in SEFR group. The good quality embryo rate was higher in VT group (72.7% vs. 63.3%, p = 0.001) compared with the singleton group. DET with subsequent VTS/SEFR carried a higher rate of adverse clinical outcomes, and the VTS group had worse perinatal outcome compared with SEFR. Therefore, we recommend SET in ART.


Force analysis and visualization of NAPL removal during surfactant-related floods in a porous medium.
Governing mechanisms of dense non-aqueous phase liquid (DNAPL) removal during surfactant and surfactant-foam (SF) flooding were studied by porous-patterned glass model experiments. Physical forces, viscous forces and capillary forces, acting on trichloroethylene (TCE) blobs were quantified to understand DNAPL removal mechanisms during the floods, simultaneously visualizing the removal mechanisms. The viscous force of the remedial fluid was intimately related to TCE removal from the porous medium. The remedial fluid with a high viscous force displaced more TCE blobs. Displacement of residual TCE by the remedial fluid began as viscous pressure of flooding was closed to the capillary pressure of the porous medium. In the region of viscous pressure less than the capillary pressure, residual TCE was either retained or solubilized, not displaced, implying that TCE solubilization was the dominant TCE removal process. Glass porous model visualization validated a dominance of the capillary forces during a surfactant flush and a dominance of the viscous forces of the displacing fluid during a SF flood.


NMDA receptor antagonists ameliorate the stepping deficits produced by unilateral medial forebrain bundle injections of 6-OHDA in rats.
To test the hypothesis that excess glutamatergic transmission at NMDA receptors may contribute to the pathogenesis of Parkinson's disease (PD), we examined the effects of various NMDA receptor antagonists on a recently developed rat model of PD. Following unilateral injections of 12 microg 6-OHDA into the medial forebrain bundle of male Long Evans rats, stepping with both front paws was measured separately as the paws were dragged backwards and laterally. The effects of i.p. injections of varying doses of L-dopa, the non-competitive NMDA receptor antagonist dizocilpine [(+)-MK-801], the competitive NMDA receptor antagonist CPP, and combinations of L-dopa and NMDA receptor antagonists were then examined on stepping in three separate groups of rats. The lesioned rats stepped less often with their contralateral paw than with their ipsilateral paw, and the magnitude of this stepping deficit was positively correlated with the amount of DA depletion in the ipsilateral dorsal striatum. L-dopa (1-25 mg/kg) dose dependently enhanced stepping with the contralateral paw, and 0.15-0.3 mg/kg dizocilpine and 1.5-6.25 mg/kg CPP enhanced stepping with the contralateral paw as much as did 8 mg/kg L-dopa. The combinations of L-dopa and each of the NMDA receptor antagonists did not significantly improve stepping more than either drug alone. Moreover, none of the drugs completely eliminated the stepping deficits, and high doses began to impair stepping with the ipsilateral paw by inducing turning. These data indicate that deficits in contralateral stepping are a reliable and sensitive measure of akinesia in unilateral 6-OHDA-lesioned rats, and they support the hypothesis that excess glutamatergic transmission at NMDA receptors may play a role in the expression of PD symptomology.


PAR3-aPKC regulates Tiam1 by modulating suppressive internal interactions.
Tiam1 is one of the most extensively analyzed activators of the small GTPase Rac. However, fundamental aspects of its regulation are poorly understood. Here we demonstrate that Tiam1 is functionally suppressed by internal interactions and that the PAR complex participates in its full activation. The N-terminal region of Tiam1 binds to the protein-binding and catalytic domains to inhibit its localization and activation. Atypical PKCs phosphorylate Tiam1 to relieve its intramolecular interactions, and the subsequent stabilization of its interaction with PAR3 allows it to exert localized activity. By analyzing Tiam1 regulation by PAR3-aPKC within the context of PDGF signaling, we also show that PAR3 directly binds PDGF receptor β. Thus we provide the first evidence for the negative regulation of Tiam1 by internal interactions, elucidate the nature of Tiam1 regulation by the PAR complex, and reveal a novel role for the PAR complex in PDGF signaling.


The gold nanoparticle size and exposure duration effect on the liver and kidney function of rats: In vivo.
Nanoparticles (NPs) offer a great possibility for biomedical application, not only to deliver pharmaceutics, but also to be used as novel diagnostic and therapeutic approaches. Currently, there are no data available regarding to what extent the degree of the toxicity and the accumulation of gold nanoparticles (GNPs) are present in in vivo administration. This study aimed to address the GNP size and exposure duration effect on the liver and kidney function of rats: in vivo. A total of 30 healthy male Wistar-Kyoto rats of the same age (12 weeks old) and weighing 220-240 g of King Saud University colony were used. Animals were randomly divided into groups, two GNP-treated rat groups and one control group (CG). The 50 μl of 10 and 50 nm GNPs was intraperitoneally administered in rats for exposure duration of 3 days. Then, several biochemical parameters such as aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alanine transaminase (ALT), alkaline phosphatase (ALP), urea (UREA) and creatinine (CREA) were evaluated. In this study, the AST values increased with the administration of 10 and 50 nm GNPs compared with the control. The AST values significantly increased with 10 nm GNPs compared with 50 nm GNPs and control. The GGT and ALT values decreased with the administration of 10 and 50 nm GNPs compared with the control. The GGT and ALT values significantly decreased with 50 nm GNPs compared with 10 nm GNPs and control. The ALP values significantly decreased with the administration of 10 and 50 nm GNPs compared with the control. The decrease in ALP values with 10 nm GNPs was higher than those compared with 50 nm GNPs. In this study, the levels of UREA and CREA values increased in a non significant manner after the administration of 10 and 50 nm GNPs compared with the control. This study demonstrates that the increase in the enzymes AST and the decrease in ALP are smaller GNPs (10 nm) size-dependent for exposure duration of 3 days; while the decrease in the enzymes GGT and ALT are bigger GNPs (50 nm) size-dependent. The levels of UREA and CREA values indicated no significant changes with the administration of 10 and 50 nm GNPs for exposure duration of 3 days compared with the control. The administration of 10 and 50 nm GNPs for short exposure duration of 3 days induced only significant variations with some liver enzymes while kidney showed no significant variations. This study suggests that synthesis and metabolism of GNPs as well as the protection of the liver will be more important issues for medical applications of gold-based nanomaterials in future.


Nasopharyngeal carcinoma.
Nasopharyngeal carcinoma is an interesting disease given its multiple histologic patterns and diverse etiology. The purpose of this paper is to review the many intriguing features of this illness. The epidemiology, staging, diagnosis, and treatment of this disease are detailed.


Intrinsic difference in beat frequency between the two flagella of Chlamydomonas reinhardtii.
The flagellar beat frequency of the biflagellated green alga Chlamydomonas reinhardtii was measured by fast Fourier transform analysis of the light intensity fluctuation in microscope images of swimming cells. Live cells had a mean beat frequency of 48-53 Hz at 20 degrees C. However, detergent-extracted "cell models," when reactivated in the presence of 1 mM ATP, appeared to have two different beat frequencies of about 30 and 45 Hz. Measurements in cell models in which only one of the two flagella was beating indicated that the lower and higher frequencies most likely represented the beat frequency of the flagellum nearer to the eyespot (the cis-flagellum) and that of the flagellum farther from it (the trans-flagellum), respectively. In live cells also, the trans-flagellum beat at a frequency about 30% higher than that of the cis-flagellum when the cells were rendered uniflagellated by mechanical treatment, whereas both flagella beat at the frequency of the cis-flagellum under normal conditions. These observations suggest that the two flagella of Chlamydomonas have different intrinsic beat frequencies but that they are somehow synchronized when beating together on a live swimming cell.


Complete amino acid sequences and phosphorylation sites, determined by Edman degradation and mass spectrometry, of rat parotid destrin- and cofilin-like proteins.
Beta-adrenergic or cholinergic stimulation of the rat parotid gland was earlier shown to induce dephosphorylation of endogenous destrin- and cofilin-like proteins, which are phosphorylated in resting cells at Ser residues probably present near the N-terminals. The primary structures and phosphorylation sites were determined here. The rat destrin-like protein had a sequence 95% identical to the cDNA-derived sequence of porcine destrin. The rat cofilin-like protein was 98% identical to that of porcine cofilin. Each protein lacked the initiator Met and began with an acetylalanine residue followed by a Ser residue. The N-terminal peptides generated with endoproteinase Asp-N were isolated; they were each phosphorylated at Ser-2. Earlier work had shown that partial cleavage of the phosphorylated destrin- and cofilin-like proteins with cyanogen bromide provides unphosphorylated 16.7- and 18.3-kDa fragments, respectively. It was here confirmed that they contained all the Ser residues other than those present in the N-terminal peptides. From these observations, it was now concluded that the destrin- and cofilin-like proteins are rat parotid destrin and cofilin (non-muscle type), respectively, and that each protein is phosphorylated exclusively at Ser-2 in resting cells and dephosphorylated at this site in response to beta-adrenergic or cholinergic stimulation.


NOB suppression strategies in a mainstream membrane aerated biofilm reactor under exceptionally low lumen pressure.
Integrating the aeration-efficient membrane aerated biofilm reactor (MABR) with anaerobic ammonium oxidation (anammox) could yield further reduction in energy in wastewater treatment facilities. However, nitrite oxidizing bacteria (NOB) suppression remained challenging due to the absence of intrinsic inhibition factors in mainstream conditions. This study investigated selective NOB suppression strategies in MABR under <5 kPa lumen pressure. Three MABRs were seeded from different seeding sludge, and operated under various ammonium loading rates, aeration pressure, and temporary inhibitory shock conditions. The three reactors were operated for 170-456 days depending on studied parameters. The results showed that higher ammonium loading could create a substrate-oxygen imbalance and quickly contain emergent NOB activity when aeration pressure was not excessive. In addition, lowering of aeration pressure reversed nitrite oxidizing activities without affecting ammonium oxidizing bacteria (AOB). Cultivating partial nitritation biofilm under zero positive aeration pressure slowed down the growth of NOB yet resulted in self-induced anammox activities. With the aid of temporary free ammonia (FA)/free nitrous acid (FNA) treatment, full-nitrifying biofilm could be transformed to stable partial nitritation biofilm. More than 84% nitrite accumulation ratio (NAR) was sustained during stable operation in each reactor together with an ammonium removal rate of more than 100 mg-N/L/d. Microbial analysis revealed that Nitrosomonas was the main AOB taxon in the three reactors while K-strategist Nitrospira showed presence despite low nitrite oxidizing activities. Under zero positive pressure, proliferation of Nitrospira was much slower while Candidatus Brocadia was self-induced. Furthermore, Nitrospira showed downturn after temporary inhibition treatment.


Immunization practices in solid organ transplant recipients.
Vaccine-preventable diseases are a significant cause of morbidity and mortality in solid organ transplant recipients who undergo immunosuppression after transplantation. The primary strategy for immunizing transplant recipients is to deliver all potential vaccines prior to transplantation. However, time constraints limit the number of vaccines that may be delivered. In such cases, the administration of live attenuated vaccines that are contraindicated after transplantation should be prioritized. Simultaneous vaccination is also encouraged to maximize the number of vaccines delivered. Immunity induced by both inactivated and live vaccines wane after transplantation. The limited but available evidence suggests that immunization using inactivated vaccines in transplant recipients is both effective and safe. An increasing number of studies also suggest that once patients are under minimal immunosuppression, live attenuated vaccines may be given effectively and safely. The need for serologic monitoring and booster immunizations remain issues for future research.


"Proactive" management of percutaneously inserted central catheters results in decreased incidence of infection in the ELBW population.
Extremely low birth weight (ELBW) infants often acquire catheter-related infections (CRIs) when a percutaneously inserted central catheter (PICC) is used for parenteral nutrition or drug administration. Our objective was to compare the incidence of CRIs after we established a "PICC Maintenance Team" for the proactive management--compared to expectant management--of these lines. We did a prospective collection and analysis of catheter-related sepsis data over a 15-month period from February 1, 1998 through May 1, 1999. Eligible patients included all neonates weighing <1000 g at birth. There was a significantly decreased incidence of CRIs, to a rate of 7.1%, or 5.1/1000 catheter days (p<0.05). "Proactive" management of PICC, significantly reduced the incidence of CRIs. The reduction in infection rate is estimated to save 180 hospitalized patient days/100 very low birth weight neonates, with a concomitant savings in morbidity and medical expense.


Bioaugmentation of Enterobacter cloacae AKS7 causes an enhanced degradation of low-density polyethylene (LDPE) in soil: a promising approach for the sustainable management of LDPE waste.
Enterobacter cloacae AKS7 was previously reported to degrade UV-treated low-density polyethylene (LDPE) more efficiently than UV-untreated LDPE. However, the degradation of LDPE by Enterobacter cloacae AKS7 at the LDPE-contaminated soil remained unaddressed. To address this issue, soil microcosms were prepared in which an equal amount of either UV-treated or UV-untreated LDPE was added. Then, the microcosms were either augmented with AKS7 or left non-augmented. We observed that the bioaugmented microcosms exhibited approximately twofold greater polymer degradation than non-bioaugmented microcosms. To investigate the underlying cause, we found that the abundance of LDPE-degrading organisms got increased by approximately fivefold in bioaugmented microcosms than non-bioaugmented microcosms. The microbial biomass carbon and nitrogen content got enhanced by approximately twofold in bioaugmented microcosms as contrasted to non-bioaugmented microcosms. Furthermore, the bioaugmented microcosms showed almost twofold increase in the level of dehydrogenase and fluorescein diacetate (FDA) hydrolyzing activity than the non-bioaugmented microcosms. To add on, Shannon-diversity index and Gini coefficient were determined in each microcosm to measure the microbial richness and evenness, respectively, using the results of carbon source utilization pattern of BiOLOG ECO plate. The bioaugmented microcosms exhibited ~ 30% higher functional richness and ~ 30% enhanced functional evenness than the non-bioaugmented microcosms indicating the formation of an enriched ecosystem that could offer various functions including polymer degradation. Taken together, the results suggested that Enterobacter cloacae AKS7 could be used as a promising bioaugmenting agent for the sustainable degradation of LDPE waste at a contaminated site.


Potential roles of insect Tropomyosin1-X1 isoform in the process of Candidatus Liberibacter asiaticus infection of Diaphorina citri.
The Asian citrus psyllid (ACP), Diaphorina citri Kuwayama, is the transmitting vector of Candidatus Liberibacter asiaticus (CLas), which causes citrus disease Huanglongbing (HLB). In recent years, control of HLB has been achieved by reducing the vector population. In the present study, we identified an isoform of D. citri tropomyosin (herein designated as DcTm1-X1). DcTm1-X1 was down-regulated in CLas-infected ACPs compared with uninfected ACPs. Bioinformatics analysis revealed that the full-length DcTm1-X1 is 2955 bp and encodes a protein of 284 amino acids with a deduced molecular weight of 32.15 kDa. Phylogenetic tree analysis suggested that DcTm1-X1 shares a high amino acid identity with its homolog in Acyrthosiphon pisum. Higher DcTm1-X1 expression levels were found in the leg of the psyllid by reverse transcription quantitative PCR (RT-qPCR). According to Blue Native PAGE analysis and mass spectrometric analysis, DcTm1-X1 interacts with citrate synthase (CS) and V-type proton ATPase subunit B-like (VAT). In addition, knockdown of DcTm1-X1 by RNA interference (RNAi) significantly increased the mortality rate of nymphs and the infection rate of CLas at different time points. Taken together, our results show that DcTm1-X1 might play an important role in response to CLas, but also lay a foundation for further research on the functions of DcTm1-X1.


Lower incidence of postdural puncture headache using whitacre spinal needles after spinal anesthesia: A meta-analysis.
The aim of this meta-analysis was to evaluate the postdural puncture headache after spinal anesthesia with Whitacre spinal needles compared with Quincke spine needles. We searched several databases, including PubMed, Embase, ISI Web of Knowledge, and Cochrane Central Register of Controlled Trials until October 10th, 2014, for randomized controlled trials that compared spinal anesthesia with Whitacre spinal needles or Quincke spine needles for postdural puncture headache. Two reviewers independently screened the literature, assessed the risk for bias and extracted data. We used RevMan 5.3 software to perform the meta-analysis. Studies were included for the main end points if they addressed the following: frequency of postdural puncture headache, severity of postdural puncture headache as assessed by limitation of activities, and frequency of epidural blood patch. Nine randomized controlled trials were included for meta-analysis. The meta-analysis showed that spinal anesthesia with Whitacre spinal needles achieved lower incidence of postdural puncture headache(RR 0.34; 95% CI [0.22, 0.52]; P < .00001); in addition, the severity of postdural puncture headache was lower in the Whitacre spinal needle group (RR 0.32; 95% CI [0.16, 0.66]; P = .002). Furthermore, the frequency of an epidural blood patch in the Whitacre spinal needle group was lower compared with that in the Quincke spine needle group (RR 0.15; 95% CI [0.04, 0.51]; P = .002). We suggest the Whitacre spinal needles as a superior choice for spinal anesthesia compared with Quincke spine needles.


Cost-effectiveness of bivalirudin in pediatric ventricular assist devices.
Despite recent data suggesting improved outcomes with bivalirudin vs heparin in pediatric Ventricular assist devices (VAD), higher costs remain a barrier. This study quantified trends in bivalirudin use and compared outcomes, resource utilization, and cost-effectiveness associated with bivalirudin vs heparin. Children age 0 to 6 year who received VAD from 2009 to 2021 were identified in Pediatric Health Information System. Bivalirudin use was evaluated using trend analysis and outcomes were compared using Fine-Gray subdistrubtion hazard ratios (SHR). Daily-level hospital costs were compared due to differences in length of stay. Cost-effectiveness was evaluated using incremental cost-effectiveness ratio (ICER). Of 691 pediatric VAD recipients (median age 1 year, IQR 0-2), 304 (44%) received bivalirudin with 90% receiving bivalirudin in 2021 (trend p-value <0.01). Bivalirudin had lower hospital mortality (26% vs 32%; adjusted SHR 0.57, 95% CI 0.40-0.83) driven by lower VAD mortality (20% vs 27%; adjusted SHR 0.46, 95% CI 0.32-0.77) after adjusting for year, age, diagnosis, and center VAD volume. Post-VAD length of stay was longer for bivalirudin than heparin (median 91 vs 64 days, respectively, p < 0.001). Median daily-level costs were lower among bivalirudin (cost ratio 0.87, 95% CI 0.79-0.96) with higher pharmacy costs offset by lower imaging, laboratory, supply, and room/board costs. Estimated ICER for bivalirudin vs heparin was $61,192 per quality-adjusted life year gained with a range of $27,673 to $131,243. Bivalirudin use significantly increased over the past decade and is now used in 90% young pediatric VAD recipients. Bivalirudin was associated with significantly lower hospital mortality and an ICER <$65,000, making it a cost-effective therapy for pediatric VAD recipients.


Elastic Modulus and Its Relation to Apparent Mineral Density in Juvenile Equine Bones of the Lower Limb.
Density-modulus relationships are necessary to develop finite element models of bones that may be used to evaluate local tissue response to different physical activities. It is unknown if juvenile equine trabecular bone may be described by the same density-modulus as adult equine bone, and how the density-modulus relationship varies with anatomical location and loading direction. To answer these questions, trabecular bone cores from the third metacarpal (MC3) and proximal phalanx (P1) bones of juvenile horses (age <1 yr) were machined in the longitudinal (n = 134) and transverse (n = 90) directions and mechanically tested in compression. Elastic modulus was related to apparent computed tomography density of each sample using power law regressions. We found that density-modulus relationships for juvenile equine trabecular bone were significantly different for each anatomical location (MC3 versus P1) and orientation (longitudinal versus transverse). Use of the incorrect density-modulus relationship resulted in increased root mean squared percent error of the modulus prediction by 8-17%. When our juvenile density-modulus relationship was compared to one of an equivalent location in adult horses, the adult relationship resulted in an approximately 80% increase in error of the modulus prediction. Moving forward, more accurate models of young bone can be developed and used to evaluate potential exercise regimens designed to encourage bone adaptation.


Immunochemical detection of the Thomsen-Friedenreich antigen (T-antigen) on platelet plasma membranes.
Platelet plasma membranes were found to possess the disaccharide beta-D-galactosyl (1-3)-N-acetyl-D-galactosamine which was measured by gas chromatography after release by alkaline borohyride treatment and desialylation. Immunological evidence using the specific lectins from Arachis hypogoea and Agaricus bisporus and an anti-T serum confirmed the presence of this disaccharide, the immunodominant group of the Thomsen-Friedenreich antigen (T-antigen). This receptor was only found after prior neuraminidase treatment indicating that it is normally a cryptic antigen, i.e. masked by sialic acid in the native membrane. Evidence for a second receptor with terminal N-acetylgalactosamine was obtained using the lectin from Helix pomatia. The binding of myxovirus and the lectins from Phaseolus vulgaris (PHA) and Canavalia ensiformis (Con A) to platelet membrane was also demonstrated. The implication of the T-antigen in elimination of the platelets and its role in the haemolytic-uraemic syndrome is discussed.


A model for the temperature distribution in skin noxiously stimulated by a brief pulse of CO2 laser radiation.
The application of localized noxious heat stimuli to the skin, generated by brief infrared radiation pulses emitted by a CO2 laser, is a relatively new experimental technique for the thermal induction of pain in humans and in experimental animals. This study proposes a model for the spatial (3-dimensional) and temporal distribution of the skin temperature during and following a radiation pulse. The heat equation is written and solved, using thermal and optical constants of human skin reported in the literature. The solution is approximated, with a very small error, by a closed form expression, having a simple physical interpretation. This model is applied to analyze a typical set-up currently in use in our laboratory. The results show a significant difference between the temperature of the surface of the skin and that of the border between the epidermis and the dermis, which is the location of the most superficial receptive nerve ends. It is shown that, for the set-up examined, these nerve ends reach a temperature of 45 degrees C, known to be the human pain threshold, 30-40 ms after pulse onset. Moreover, it is also shown that they may remain above threshold temperature for up to a few hundreds of milliseconds (considerably outlasting pulse cessation). In addition, it is shown that the area in which nerve ends reach this threshold is a circle with a very small radius (1-2.5 mm). The implications of the results on the double sensation experienced by humans, and on the extremely powerful EEG correlates, are discussed.


A method for constructing word sense embeddings based on word sense induction.
Polysemy is an inherent characteristic of natural language. In order to make it easier to distinguish between different senses of polysemous words, we propose a method for encoding multiple different senses of polysemous words using a single vector. The method first uses a two-layer bidirectional long short-term memory neural network and a self-attention mechanism to extract the contextual information of polysemous words. Then, a K-means algorithm, which is improved by optimizing the density peaks clustering algorithm based on cosine similarity, is applied to perform word sense induction on the contextual information of polysemous words. Finally, the method constructs the corresponding word sense embedded representations of the polysemous words. The results of the experiments demonstrate that the proposed method produces better word sense induction than Euclidean distance, Pearson correlation, and KL-divergence and more accurate word sense embeddings than mean shift, DBSCAN, spectral clustering, and agglomerative clustering.


[Evidence-based Lichtenstein technique].
Lichtenstein hernioplasty is the number one technique worldwide for open, mesh-based inguinal hernia repair. The principle of Lichtenstein hernioplasty is the tension-free reinforcement of the abdominal wall by covering the transversalis fascia and the oblique muscles with an artificial patch of mesh. The Lichtenstein technique has been modified since its inception. The technique has the benefits of low costs and a rapid learning curve and can be performed with the patient under local anesthesia. The recurrence rates after the Lichtenstein operation are significantly lower compared to open suture repair and equal to laparoendoscopic techniques. Compared to laparoendoscopic techniques the Lichtenstein operation is associated with less severe visceral lesions but more early postoperative and chronic pain; however, the chronic pain rates in long-term follow-up studies are comparable.


Spontaneous ligamentum flavum hematoma in the lumbar spine.
Lumbar or sacral nerve root compression is most commonly caused by intervertebral disc degeneration and/or herniation. Less frequently, other extradural causes may be implicated, such as infection, neoplasm, epidural hematoma, or ligamentum flavum pathology. We present the case of a patient with spontaneous ligamentum flavum hematoma compressing the L4 nerve root, without antecedent trauma. Although exceedingly rare, the diagnosis of ligamentum flavum pathology in general, and that of ligamentum flavum hematoma in particular, should be considered on those rare occasions when the etiology of lumbar or sacral nerve root compressions appears enigmatic on radiological studies. Usually surgical treatment produces excellent clinical outcome.