Online interest in surgical treatment for benign prostatic hyperplasia using Google trends.
Online health information-seeking behavior has increased over the past 15 years; however, little is known about the online interest for surgical treatment of men with benign prostatic hyperplasia. We used Google Trends to evaluate online interest for various surgical procedures for benign prostatic hyperplasia in the US and worldwide. Transurethral resection of the prostate, photoselective vaporization of the prostate, Holmium laser enucleation of the prostate, Urolift, and Rezum were selected as search terms of interest within Google Trends. Google Trends normalizes the popularity of search terms on a 0-100 scale. ANOVA and the average rate of change in popularity scores were conducted from July 2015 to February 2019. From 2004 to 2019, online interest in transurethral resection of the prostate and photoselective vaporization of the prostate remained stable in the US and worldwide; meanwhile, there was an upward trend for Urolift and Rezum. There was a statistically significant increase in the online interest for Holmium laser enucleation of the prostate in the US and worldwide; however, the mean popularity score was significantly higher worldwide. A shift in online interest towards minimally invasive surgical therapies for benign prostatic hyperplasia was demonstrated in the US and worldwide and parallels clinical practice patterns, such as HoLEP and Urolift surgical volumes in Indiana and Australia, respectively. Google Trends can be used in real-time to gauge online interest for surgical procedures and help guide physician-patient counseling.


Metabolic Heterogeneity, Plasticity, and Adaptation to "Glutamine Addiction" in Cancer Cells: The Role of Glutaminase and the GTωA [Glutamine Transaminase-ω-Amidase (Glutaminase II)] Pathway.
Many cancers utilize l-glutamine as a major energy source. Often cited in the literature as "l-glutamine addiction", this well-characterized pathway involves hydrolysis of l-glutamine by a glutaminase to l-glutamate, followed by oxidative deamination, or transamination, to α-ketoglutarate, which enters the tricarboxylic acid cycle. However, mammalian tissues/cancers possess a rarely mentioned, alternative pathway (the glutaminase II pathway): l-glutamine is transaminated to α-ketoglutaramate (KGM), followed by ω-amidase (ωA)-catalyzed hydrolysis of KGM to α-ketoglutarate. The name glutaminase II may be confused with the glutaminase 2 (GLS2) isozyme. Thus, we recently renamed the glutaminase II pathway the "glutamine transaminase-ω-amidase (GTωA)" pathway. Herein, we summarize the metabolic importance of the GTωA pathway, including its role in closing the methionine salvage pathway, and as a source of anaplerotic α-ketoglutarate. An advantage of the GTωA pathway is that there is no net change in redox status, permitting α-ketoglutarate production during hypoxia, diminishing cellular energy demands. We suggest that the ability to coordinate control of both pathways bestows a metabolic advantage to cancer cells. Finally, we discuss possible benefits of GTωA pathway inhibitors, not only as aids to studying the normal biological roles of the pathway but also as possible useful anticancer agents.


Metallic nanoplatforms for COVID-19 diagnostics: versatile applications in the pandemic and post-pandemic era.
The COVID-19 pandemic, which originated in Hubei, China, in December 2019, has had a profound impact on global public health. With the elucidation of the SARS-CoV-2 virus structure, genome type, and routes of infection, a variety of diagnostic methods have been developed for COVID-19 detection and surveillance. Although the pandemic has been declared over, we are still significantly affected by it in our daily lives in the post-pandemic era. Among the various diagnostic methods, nanomaterials, especially metallic nanomaterials, have shown great potential in the field of bioanalysis due to their unique physical and chemical properties. This review highlights the important role of metallic nanosensors in achieving accurate and efficient detection of COVID-19 during the pandemic outbreak and spread. The sensing mechanisms of each diagnostic device capable of analyzing a range of targets, including viral nucleic acids and various proteins, are described. Since SARS-CoV-2 is constantly mutating, strategies for dealing with new variants are also suggested. In addition, we discuss the analytical tools needed to detect SARS-CoV-2 variants in the current post-pandemic era, with a focus on achieving rapid and accurate detection. Finally, we address the challenges and future directions of metallic nanomaterial-based COVID-19 detection, which may inspire researchers to develop advanced biosensors for COVID-19 monitoring and rapid response to other virus-induced pandemics based on our current achievements.


Effects of tail fat on halothane biotransformation in fat-tailed sheep.
1. The aim of the present study was to evaluate the effects of tail fat on halothane biotransformation following similar anaesthetic exposure in intact sheep and sheep with a ligated median sacral artery. 2. A prospective randomized experimental study was performed using 12 healthy, 10-12-month-old female sheep. 3. Sheep were randomly divided into two groups of six animals each and were anaesthetized twice at 2 weekly intervals. After mask induction with halothane in 100% oxygen, sheep were intubated and anaesthesia was maintained for 3 h using a rebreathing system. Serum fluoride concentration (SFC) was measured at 0, 1, 3, 6, 12, 24, 48 and 72 h following the induction of anaesthesia. Serum biochemistry was also evaluated at baseline and 72 h after anaesthesia. Induction and extubation times and time to sternal recumbency were also recorded during anaesthetic induction and recovery. Prior to the second anaesthesia (2 weeks later), the median sacral artery (MSA) was ligated under epidural anaesthesia in the experimental group. Sheep in the control group underwent sham operation. All sheep were anaesthetized as before. 4. Following the first halothane anaesthesia, SFC was significantly increased from 3 to 48 h compared with baseline. In the second stage of the experiment, the increases in SFC in the control group were similar to those seen in the first stage of the experiment. However, in MSA-ligated sheep, the increases in SFC were only significant between 3 and 12 h compared with baseline. The SFC was significantly higher in intact sheep from 3 to 72 h compared with the MSA-ligated group. Extubation and sternal recumbency times were significantly longer in intact sheep. 5. Ligation of the MSA in fat-tailed sheep induced a significant reduction in SFC, suggesting that the presence of tail fat substantially affects halothane metabolism during the peri-anaesthetic period in sheep. The greater extent of halothane biotransformation may be clinically important in, otherwise normal, obese patients.


Experimental ileal J-pouch construction. A comparison of three techniques.
Endorectal ileal pouch-anal anastomosis has become the surgical alternative of choice for patients requiring colectomy for ulcerative colitis or familial polyposis coli. The optimal method of ileal pouch construction has not been determined. In this study, a canine preparation was used to compare the immediate results of three different techniques of ileal J-pouch construction. The three methods studied were two-layer hand-suturing (HS), stapling through enterotomies placed laterally on the ileal limbs (LS), and stapling via an apically placed enterotomy (AS). All three techniques resulted in watertight reservoirs. Ease of construction was scored significantly differently among the pouch variations (AS greater than LS greater than HS). Construction time was significantly less for both of the stapled reservoirs than for the HS pouch. Capacity of the AS pouch was significantly greater than the HS reservoir. This study suggests that stapling the ileal J-pouch through a single apical enterotomy should be the preferred technique during colectomy, mucosal proctectomy, and ileal pouch-anal anastomosis.


Design, synthesis and molecular docking and ADME studies of novel hydrazone derivatives for AChE inhibitory, BBB permeability and antioxidant effects.
Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disease that is characterized by memory and cognitive impairments that predominantly affects the elderly and is the most common cause of dementia. As is known, the AChE enzyme consists of two parts. In this work, 10 new hydrazones (3a-3j) were designed and synthesized. Naphthalene, indole, benzofuran and benzothiophene rings were used to interact with the PAS region. 4-fluorophenyl and 4-fluorobenzyl structures were preferred for interaction with the CAS region. In biological activity studies, the AChE and BChE inhibitory potentials of all compounds were evaluated using the in vitro Ellman method. The biological evaluation showed that compounds 3i and 3j displayed significant activity against AChE. The compounds 3i and 3j displayed IC50 values of 0.034 and 0.027 µM against AChE, respectively. The reference drug donepezil (IC50 = 0.021 µM) also displayed a significant inhibition against AChE. In addition, the antioxidant activities of the compounds were also evaluated. Derivatives 3i and 3j, which emerged active from both in vitro activity studies, were subjected to in vitro PAMPA tests to determine BBB permeability. Further docking simulation also revealed that these compounds (3i, 3j and donepezil) interacted with the enzyme active site in a similar manner to donepezil. A few parameters derived from MD simulation trajectories were computed and validated for the protein-ligand complex's stability under the dynamic conditions.Communicated by Ramaswamy H. Sarma.


Comparative study of carbazochrome sodium sulfonate and tranexamic acid in reducing blood loss and inflammatory response following direct anterior total hip arthroplasty: a prospective randomized controlled trial.
Carbazochrome sodium sulfonate (CSS) is a haemostatic agent. However, its hemostatic and anti-inflammatory effects in patients undergoing total hip arthroplasty (THA) via a direct anterior approach (DAA) are unknown. We investigated the efficacy and safety of CSS combined with tranexamic acid (TXA) in THA using DAA. This study enrolled 100 patients who underwent primary, unilateral THA through a direct anterior approach. Patients were randomly divided into two groups: Group A used a combination of TXA and CSS, while Group B used TXA only. The primary outcome was total perioperative blood loss. The secondary outcomes were hidden blood loss, postoperative blood transfusion rate, inflammatory reactant levels, hip function, pain score, venous thromboembolism (VTE), and incidence of associated adverse reactions. The total blood loss (TBL) in group A was significantly lower than in group B. The levels of inflammatory reactants and the rate of blood transfusion were also significantly lower. However, the two groups had no significant differences in intraoperative blood loss, postoperative pain score, or joint function. There were no significant differences in VTE or postoperative complications between the groups. As a haemostatic agent, CSS combined with TXA can reduce postoperative blood loss in patients undergoing THA via DAA and seems to have an anti-inflammatory effect. Moreover, it did not increase the incidence of VTE or its related complications.


Extraction of osmium-containing lipids by section staining for TEM.
Postfixation with osmium-ferrocyanide or OSO4 renders lipid droplets in rat liver and kidney homogeneously electron dense without additional section staining. In sections of the same block that have been single stained by uranyl acetate or lead citrate, lipid droplets show a more electron translucent center surrounded by a dense rim. In sections double stained with uranyl acetate and lead citrate, lipid droplets frequently appear as empty vacuoles, from which the electron dense content has been completely extracted.


Application of factorial design and Doehlert matrix for determination of trace lead in environmental samples by on-line column preconcentration FAAS using silica gel chemically modified with niobium(V) oxide.
In this study a new method for Pb determination in water using solid phase extraction coupled to a flow injection system and flame atomic absorption spectrometry was developed. The sorbent used for Pb preconcentration and extraction was silica gel chemically modified with niobium(V) oxide. Flow and chemical variables of the system were optimized through a multivariate procedure. The factors selected were buffer type, eluent concentration, and sample and eluent flow rates. It was verified that the aforementioned factors as well as their interactions were statistically significant at the 95% confidence level. The effect of foreign ions was evaluated using a fractionary factorial experimental design. The detection limit was 0.35 microg L(-1) and the precision was 1.6%. Results for recovery tests using different environmental samples were between 90 and 104%. Certified reference materials were analyzed in order to check the accuracy of the proposed method.


Transplantation of platelet gel spiked with cardiosphere-derived cells boosts structural and functional benefits relative to gel transplantation alone in rats with myocardial infarction.
The emerging field of stem cell therapy and biomaterials has begun to provide promising strategies for the treatment of ischemic cardiomyopathy. Platelet gel and cardiosphere-derived cells (CDCs) are known to be beneficial when transplanted separately post-myocardial infarction (MI). We hypothesize that pre-seeding platelet gel with CDCs can enhance therapeutic efficacy. Platelet gel and CDCs were derived from venous blood and heart biopsies of syngeneic rats, respectively. In vitro, the viability, growth, and morphology of CDCs cultured in platelet gel were characterized. When delivered into infarcted rat hearts, platelet gel pre-seeded with CDCs was more efficiently populated with endogenous cardiomyocytes and endothelial cells than platelet gel alone. Recruitment of endogenous c-kit positive cells was enhanced in the hearts treated with gel with CDC. At 3 weeks, the hearts treated with CDC-seeded platelet gel exhibited the greatest attenuation of adverse left ventricular (LV) remodeling and the highest cardiac function (i.e., LV ejection fraction) as compared to hearts transplanted with Gel only or vehicle controls. Histological analysis revealed that, though some transplanted CDCs differentiated into cardiomyocytes and endothelial cells in the recipients' hearts, most of the incremental benefit arose from CDC-mediated endogenous repair. Pre-seeding platelet gel with CDCs enhanced the functional benefit of biomaterial therapy for treating myocardial infarction.


Bacillus subtilis GlnR contains an autoinhibitory C-terminal domain required for the interaction with glutamine synthetase.
The Bacillus subtilis GlnR transcription factor regulates gene expression in response to changes in nitrogen availability. Glutamine synthetase transmits the nitrogen regulatory signal to GlnR. The DNA-binding activity of GlnR is activated by a transient protein-protein interaction with feedback-inhibited glutamine synthetase that stabilizes GlnR-DNA complexes. This signal transduction mechanism was analysed by creating mutant GlnR proteins with partial or complete truncations of their C-terminal domains. The truncated GlnR proteins were found to constitutively repress gene expression in vivo. This constitutive repression did not require glutamine synthetase. Purified mutant GlnR proteins bound DNA in vitro more tightly than wild-type GlnR protein and this binding was not activated by feedback-inhibited glutamine synthetase. While full-length GlnR is monomeric, the truncated GlnR proteins contained significant levels of dimers. These results indicate that the C-terminal region of GlnR acts as an autoinhibitory domain that prevents GlnR dimerization and thus impedes DNA binding. The GlnR C-terminal domain is also required for the interaction between GlnR and feedback-inhibited glutamine synthetase. Compared with the full-length GlnR protein, the truncated GlnR proteins were defective in their interaction with feedback-inhibited glutamine synthetase in cross-linking experiments.


The Cdk5 inhibitor β-butyrolactone impairs reconsolidation of heroin-associated memory in the rat basolateral amygdala.
The persistence of maladaptive heroin-associated memory, which is triggered by drug-related stimuli that remind the individual of the drug's pleasurable and rewarding effects, can impede abstinence efforts. Cyclin-dependent kinase 5 (Cdk5), a neuronal serine/threonine protein kinase that plays a role in multiple neuronal functions, has been demonstrated to be involved in drug addiction and learning and memory. Here, we aimed to investigate the role of cdk5 activity in the basolateral amygdala (BLA) in relapse to heroin seeking, using a self-administration rat model. Male rats underwent 10 days of heroin self-administration training, during which an active nose poke resulted in an intravenous infusion of heroin that was accompanied by a cue. The rats then underwent nose poke extinction for 10 days, followed by subsequent tests of heroin-seeking behaviour. We found that intra-BLA infusion of β-butyrolactone (100 ng/side), a Cdk5 inhibitor, administered 5 min after reactivation, led to a subsequent decrease in heroin-seeking behaviour. Further experiments demonstrated that the effects of β-butyrolactone are dependent on reactivated memories, temporal-specific and long-lasting on relapse of heroin-associated memory. Results provide suggestive evidence that the activity of Cdk5 in BLA is critical for heroin-associated memory and that the specific inhibitor, β-butyrolactone, may hold potential as a substance for the treatment of heroin abuse.


A spermatogenesis-related gene expression profile in human spermatozoa and its potential clinical applications.
Spermatogenesis is an essential stage in the human reproductive process. In a previously study aiming to determine which genes might be involved in spermatogenesis, we compared the gene expression profiles of adult and fetal testes by hybridizing cDNA probes prepared from adult and fetal testes to membranes dotted with gene clones derived from a commercial human testis library. We identified 266 differentially expressed genes that showed higher expression levels in adult testes, indicating their potential roles in spermatogenesis. In the present study, we applied the same cDNA microarray technique to the analysis of gene expression in the spermatozoa of normal fertile men and found 149 genes that were expressed at higher levels in adult testis. A further study of five sperm motility-related genes selected from this profile by real-time PCR revealed that there was significant difference in the expression levels of two genes ( TPX-1, testis-specific protein 1 and LDHC, lactate dehydrogenase C, transcript variant 1) between normal ( n=29) and motility impaired ( n=24) semen samples, indicating that these genes are involved in sperm function. Our results demonstrated that spermatogenesis-related gene profiling could help to assess sperm quality in humans, and further study of these genes will help us to elucidate the mechanisms involved in spermatogenesis and diseases relating to human infertility.


Serum glycoproteins in the liver diseases. VI. The presence of desialylated glycoprotein binding activity in particulate fraction of human liver homogenate.
The human liver as well as rat liver particulate fraction was determined to have an ability to bind desialylated alpha 1-acid glycoprotein. The binding activity of human liver was the same order of the rat one. A more increased amount of binding of desialylated glycoprotein was found in a new born liver than an adult one. Serum obtained from a cirrhotic patient inhibited the binding. The sucrose density gradient centrifugation revealed that the activity located partly in fractions in which a membrane enzyme, alkaline phosphatase, was detected. The binding activity was a linear function of concentration of human liver particulate fraction added to incubation mixture.


Age-dependent physiochemical and biochemical studies of human red cell membranes.
Erythrocyte ghosts of male persons of two age groups, younger than thirty and older than seventy years, were analyzed to investigate the imfluence of age on lipid composition, the physical state of the lipid phase, Na+K+-ATPase activity and sialic acid content. The phospholipid content in red cell membranes of old donors is significantly lower than in young ones. Cholesterol and fatty acid compositions shows no difference between the two donor groups. The membrane fluidity in liposomes prepared from total lipids of old donor decreased. No significant difference in lipid composition and membrane fluidity reflected by the spin labels was observed between blood group A and O. The activity of Na+K+-ATPase of the young donors with blood group A is significantly higher than those of old donors. The results also demonstrate a decrease of sialic acid content of red cells of old donors.


Effect of postischaemic hypothermia on the mitochondrial damage induced by ischaemia and reperfusion in the gerbil.
In order to test the effect of hypothermia on mitochondrial function damage following cerebral ischaemia/reperfusion, Mongolian gerbils were submitted to 30 min bilateral carotid occlusion and 2 h of reperfusion at 37 degreesC or 30 degreesC. After normothermic (37 degreesC) ischaemia/reperfusion, significant decreases in mitochondrial state 3 (+ADP) oxygen consumption (-42.2%), complex II-III activity in synaptosomes (-31.7%) and complex IV were measured, in both free mitochondria and synaptosomes (-30.3% and -27. 8% respectively). However, following hypothermic (30 degreesC) reperfusion, both respiration rates and all enzyme activities remained at levels not significantly different from those in the sham operated controls.


Lipidomics profile of a NAPE-PLD KO mouse provides evidence of a broader role of this enzyme in lipid metabolism in the brain.
A leading hypothesis of N-acyl ethanolamine (NAE) biosynthesis, including the endogenous cannabinoid anandamide (AEA), is that it depends on hydrolysis of N-acyl-phosphatidylethanolamines (NAPE) by a NAPE-specific phospholipase D (NAPE-PLD). Thus, deletion of NAPE-PLD should attenuate NAE levels. Previous analyses of two different NAPE-PLD knockout (KO) strains produced contradictory data on the importance of NAPE-PLD to AEA biosynthesis. Here, we examine this hypothesis with a strain of NAPE-PLD KO mice whose lipidome is uncharacterized. Using HPLC/MS/MS, over 70 lipids, including the AEA metabolite, N-arachidonoyl glycine (NAGly), the endocannabinoid 2-arachidonyl glycerol (2-AG) and prostaglandins (PGE(2) and PGF(2α)), and over 60 lipoamines were analyzed in 8 brain regions of KO and wild-type (WT) mice. Lipidomics analysis of this third NAPE-PLD KO strain shows a broad range of lipids that were differentially affected by lipid species and brain region. Importantly, all 6 NAEs measured were significantly reduced, though the magnitude of the effect varied by fatty acid saturation length and brain region. 2-AG levels were only impacted in the brainstem, where levels were significantly increased in KO mice. Correspondingly, levels of arachidonic acid were significantly decreased exclusively in brainstem. NAGly levels were significantly increased in 4 brain regions and levels of PGE(2) increased in 6 of 8 brain regions in KO mice. These data indicate that deletion of NAPE-PLD has far broader effects on the lipidome than previously recognized. Therefore, behavioral characteristics of suppressing NAPE-PLD activity may be due to a myriad of effects on lipids and not simply due to reduced AEA biosynthesis.


Expression of OCT4 in human esophageal squamous cell carcinoma is significantly associated with poorer prognosis.
To explore the expression pattern of OCT4 in human esophageal squamous cell carcinoma and its significance in diagnosis and prognosis. Using real-time polymerase chain reaction (PCR), Western blotting, immunocytochemistry and immunohistochemistry, the expression of OCT4 in three esophageal squamous cancer cell lines, KYSE70, KYSE140 and KYSE450, was characterized. OCT4 expression was investigated in a series of 153 esophageal squamous cell carcinoma samples using immunohistochemistry and explored its association with clinicopathological features. Immunohistochemically, OCT4 positive immunostaining was observed in cancer cell nuclei. OCT4 was variably expressed in three esophageal squamous cancer cell lines. Among 153 specimens, 105 (68.7%) were negative or weakly positive for OCT4 staining; 21 (13.7%) were moderately positive and 27 (17.6%) were strongly positive. Higher expression level of OCT4 was significantly associated with higher histological grade (P < 0.001) and poor clinic outcome (P < 0.001). The expression of OCT4 enables the tumor to have a higher degree of stemness, which in turn results in a poorer clinical outcome for patients with esophageal squamous cell carcinoma.


Problem gambling and anxiety disorders in the general swedish population - a case control study.
Co-occurring psychiatric comorbidity is high among problem gamblers, and anxiety disorders has repeatedly been linked to problem gambling. Less conclusive, however, is the association between problem gambling and specific anxiety disorders. The aim of this study is to examine the association between problem gambling and specific anxiety disorders in subgroups of gender, age and socio-economic status (SES) in the general Swedish population. A case-control design was employed - nested in the Swedish longitudinal gambling study cohort. All anxiety disorders studied - Panic Disorder, Social Phobia, Generalized Anxiety Disorder (GAD) and Post-Traumatic Stress Disorder (PTSD), were significantly associated with problem gambling, however the pattern differed across subgroups. Social Phobia was the anxiety disorder most commonly associated with problem gambling across subgroups. The strongest associations between problem gambling and various anxiety disorders were found in participants under the age of 25, among females, and in the group with middle SES. In those groups three of the four anxiety disorders studied were significantly associated with problem gambling, with different patterns. Quite remarkably, participants under the age of 25 had three times higher risk of having had GAD compared to their controls. Efforts to prevent an escalation of either gambling or anxiety could target the presented vulnerable groups specifically.


A phase II study of pemetrexed monotherapy in chemo-naïve Eastern Cooperative Oncology Group performance status 2 patients with EGFR wild-type or unknown advanced non-squamous non-small cell lung cancer (HANSHIN Oncology Group 002).
The aim of our study was to investigate the efficacy and safety of pemetrexed monotherapy in chemo-naïve Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2 patients with epidermal growth factor receptor (EGFR) wild-type or unknown advanced non-squamous non-small cell lung cancer (NSCLC). Pemetrexed was administered at 500 mg/m(2) triweekly until progression with supplementations in chemo-naïve ECOG PS 2 patients with EGFR wild-type or unknown advanced non-squamous NSCLC. Between September 2009 and April 2013, twenty-eight patients were enrolled. Median age was 75 (range 59-89). Nineteen (68 %) of 28 were ever smoker, and 18 (64 %) had pulmonary emphysema. Sixteen (57 %) had comorbidities such as hypertension, heart disease, and/or diabetes. In 26 eligible patients, the overall response rate, disease control rate, median PFS, and median overall survival were 11.5, 53.8 %, 3.0 [95 % confidence interval (CI) 1.9-5.7] months and 9.5 (95 % CI 3.3-12.5) months, respectively. Median administered course number was 3 (range 1-14). Median duration of PS maintenance ≤2 was 4.9 (95 % CI 1.3-9.7) months. Common (≥10 %) grade 3/4 toxicities included 7 (27 %) neutropenia, 7 (27 %) leukopenia, 4 (15 %) fatigue, and 3 (12 %) thrombocytopenia. Febrile neutropenia and interstitial lung disease were not observed. There were no treatment-related deaths. Pemetrexed monotherapy demonstrated moderate efficacy and good safety in chemo-naïve PS 2 patients with EGFR wild-type or unknown non-squamous NSCLC. It can be a therapeutic option in "frail" PS 2 non-squamous NSCLC patients without the indication of combination regimens, if the patient is EGFR wild-type.


Coexistence and host use by a large community of Pierid butterflies: habitat is the templet.
We report studies on the butterfly-hostplant communities in the species-rich area of west central Morocco. Pieridae feeding on Capparales form two distinct ecological guilds: inflorescence feeders and folivores. Several members of each guild may synchronously occur in sympatry. Substantial levels of cannibalism and inter-specific predation occur amongst the inflorescence feeders. No evidence was obtained for segregation of butterfy species on different hosts. Host plants included in the diet of specialists were also used by generalists. Despite substantial differences observed in laboratory trials of larval survivorship on different hostplants, results were congruent for all Pieridae, suggesting that little one-to-one insect-host coevolution has occurred. Host specialization was instead related to the year-to-year stability of host numbers in an area. High levels of pierid infestation occurred on host species with numerically stable populations. Host numerical stability was correlated with habitat type. There is little evidence for segregation of competing inflorescence feeders by hostplant species, but some evidence for segregation by habitat type (particularly by shading levels). We interpret our results as indicating that the hostplant affiliations of Moroccan Capparales-feeding Pieridae are subject to (at best) diffuse coevolutionary effects from hosts and competitors, and are strongly influenced by habitat characteristics.


Diagnosis of tetanus by an otorhinolaryngologist and immunity against tetanus among adults on the island of Crete.
Tetanus (lockjaw) is a rare disease in developed countries. An otorhinolaryngologist can be the first physician to see a patient with tetanus. In our department, we have seen 10 such cases presenting with head and neck symptoms. We report 2 of these cases followed by an investigation of the immune status of the adult Cretan population against tetanus using 200 random patients who visited our clinic. A negative history of complete childhood immunization was recorded in 37% of individuals. Of the male population, 88.5% had received active immunization during adulthood, although 47% had received all three doses. Only 12.6% of the females had received full-dose immunization during adulthood. Overall, only 8.5% of the studied population had received either complete immunization or a scheduled booster dose during the last decade. In many cases, an otorhinolaryngologist can be the first physician to examine a patient with tetanus. The incidence of the disease in Crete, Greece, is significantly higher than in most parts of developed countries.


Melatonin protects against lipid peroxidation and membrane rigidity in erythrocytes from patients undergoing cardiopulmonary bypass surgery.
The first aim of this study was to test whether there are changes in erythrocyte lipid peroxidation products and membrane fluidity during cardiac surgery involving cardiopulmonary bypass. Secondly, in vitro tests were performed to examine whether melatonin alters induced lipid peroxidation and reduced membrane fluidity in erythrocytes from these patients. Fifteen patients undergoing cardiac surgery involving cardiopulmonary bypass (CPB) were selected. Five blood samples were taken at different times during surgery for analysis of thiobarbituric acid reactive substances (TBARS) content and membrane fluidity of the erythrocytes. TBARS are an index of the level of lipid peroxidation. The results revealed an increase in TBARS levels and a parallel decrease in erythrocyte membrane fluidity (increased membrane rigidity) after the onset of CPB with respect to the reference sample. Likewise, in vitro induction of lipid peroxidation in the erythrocyte samples from CPB patients followed a similar pattern. The changes in TBARS levels and membrane fluidity were suppressed by pre-incubation of erythrocytes with melatonin prior to the induction (by 70 microm Fe2+ + 250 microm ascorbate) of lipid peroxidation in a concentration-dependent manner. The results constitute a persuasive argument for the use of melatonin for preventive and therapeutic purposes during CPB.


Mechanistic Oral Absorption Modeling of Halofantrine: Exploring the Role of Intestinal Lymphatic Transport.
Absorption via the intestinal lymphatic system is known to be important for some highly lipophilic compounds, and can be associated with unique pharmacokinetic properties due to evasion of hepatic first-pass metabolism. This work aimed to develop a physiologically-based pharmacokinetic model incorporating the role of lymphatic transport in a physiologically-based, mechanistic oral absorption model, using halofantrine as a model compound. Simcyp V19 was used for model development; oral absorption was characterized using the multi-layer gut wall (M-ADAM) model, and the model was constructed and verified using parameters derived from in vitro experiments and clinical PK data. The final model appeared to adequately capture halofantrine pharmacokinetics in the fasted state and the magnitude of the effect of food on halofantrine total exposure; the effect of food on peak exposure was slightly underpredicted, which may be due to transient post-prandial changes in protein binding. The model simulated halofantrine fraction absorbed (fa) via the lymph in the fed state was 0.26, representing 62% of the increase in fa in the fed state over fasting. This work demonstrates that a PBPK modeling approach can be used to mechanistically describe oral absorption incorporating intestinal lymphatic transport.


A case of gynandromorphism in Hyalomma anatolicum (Ixodida: Ixodidae).
We present a field-collected Hyalomma anatolicum gynandromorph in Xinjiang, China. Compared to the normal H. anatolicum, the gynandromorphic tick was a typical bipartite protogynander: half of the tick body displayed normal female traits, whereas the other side showed normal male traits. The engorged gynandromorphic tick laid hundreds of eggs, and the eggs looked normal.


Orthotopic bone formation in titanium fiber mesh loaded with platelet-rich plasma and placed in segmental defects.
The effect of platelet-rich plasma (PRP) on bone formation was investigated in a rabbit segmental radial defect model. The purpose of the study was to evaluate the bone inductive properties of PRP with titanium fiber mesh and autologous bone chips in a 15-mm rabbit radial defect model. Eighteen New Zealand white rabbits were divided into three groups: I, PRP with autologous bone (PRP-Ti-Bone); II, autologous bone (Ti-Bone); III, control group (Ti). The implants were placed in the radial defect for 12 weeks. After sacrifice, all specimens were harvested for histological, histomorphometrical and radiographic analysis. Histomorphometrical analysis showed that bone formation was higher in the implants with PRP (PRP-Ti-Bone: 37+/-8%) than in those without PRP (Ti-bone: 25+/-6% and Ti: 25+/-5%) after 12 weeks of implantation. It was concluded that PRP has a stimulatory effect on bone formation in titanium fiber mesh filled with autologous bone graft in segmental bone defects. Titanium fiber mesh was also shown to be an excellent scaffold material for the application of autologous bone grafts with or without PRP.


Analysis of Association of Ultradian Body Temperature Rhythms in Animals with Intensity of Fluctuations of Radioactive Decay of Natural 40K Isotope.
The study monitored the long-term body temperature (BT) oscillations of C57BL/6 mice and outbred starlings (Sturnus vulgaris) to compare them with fluctuation in decay rate of radioactive natural 40K isotope. The spectrum analysis revealed simultaneous changes of the predominant periods in BT spectra of the animals and those in fluctuation in 40K decay rate. A positive correlation was established between BT dynamics and fluctuation in decay rate. The superposed epoch analysis revealed predominant coincidence of the moments of BT and fluctuation in 40K decay rate. The novel data indicate association between BT ultradian rhythms with quasirhythmic variations of fluctuation in 40K decay rate.


Intermediate outcomes: diagnostic and therapeutic impact.
The conceptual basis for intermediate outcomes has been established, and scientifically sound methods are available for assessment of these short-term outcomes. While modest intermediate outcomes research experience assessing imaging technology has accumulated in the literature, much more remains to be done, for the benefit of both patients and physicians. I would recommend that intermediate outcomes research become more focused on assessment earlier in the diffusion phase of imaging technology development. These studies should be based on traditional diagnostic accuracy studies, but these should be extended to include well-designed, high scientific quality treatment impact studies. Furthermore, such studies need to be multidisciplinary and multiinstitutional/multisite and include patient utility assessment components.


Retracted: 23G Minimally Invasive Vitrectomy Combined with Glaucoma Drainage Valve Implantation and Phacoemulsification Cataract Extraction for Neovascular Glaucoma Secondary to Proliferative Diabetic Retinopathy with Vitreous Hemorrhage.
[This retracts the article DOI: 10.1155/2022/7393661.].


Si/InGaN core/shell hierarchical nanowire arrays and their photoelectrochemical properties.
Three-dimensional hierarchical nanostructures were synthesized by the halide chemical vapor deposition of InGaN nanowires on Si wire arrays. Single phase InGaN nanowires grew vertically on the sidewalls of Si wires and acted as a high surface area photoanode for solar water splitting. Electrochemical measurements showed that the photocurrent density with hierarchical Si/InGaN nanowire arrays increased by 5 times compared to the photocurrent density with InGaN nanowire arrays grown on planar Si (1.23 V vs RHE). High-resolution transmission electron microscopy showed that InGaN nanowires are stable after 15 h of illumination. These measurements show that Si/InGaN hierarchical nanostructures are a viable high surface area electrode geometry for solar water splitting.


The environmental pollutant, polychlorinated biphenyls, and cardiovascular disease: a potential target for antioxidant nanotherapeutics.
Despite production having stopped in the 1970s, polychlorinated biphenyls (PCBs) represent persistent organic pollutants that continue to pose a serious human health risk. Exposure to PCBs has been linked to chronic inflammatory diseases, such as cardiovascular disease, type 2 diabetes, obesity, as well as hepatic disorders, endocrine dysfunction, neurological deficits, and many others. This is further complicated by the PCB's strong hydrophobicity, resulting in their ability to accumulate up the food chain and to be stored in fat deposits. This means that completely avoiding exposure is not possible, thus requiring the need to develop intervention strategies that can mitigate disease risks associated with exposure to PCBs. Currently, there is excitement in the use of nutritional compounds as a way of inhibiting the inflammation associated with PCBs, yet the suboptimal delivery and pharmacology of these compounds may not be sufficient in more acute exposures. In this review, we discuss the current state of knowledge of PCB toxicity and some of the antioxidant and anti-inflammatory nanocarrier systems that may be useful as an enhanced treatment modality for reducing PCB toxicity.


Mucinous adenocarcinoma of the colon and rectum: A genomic analysis.
Mucinous adenocarcinoma is a distinct subtype of colorectal cancer (CRC) with a worse prognosis when compared with non-mucinous adenocarcinoma. The aim of this study was to compare somatic mutations and copy number alteration (CNA) between mucinous and non-mucinous CRC. Data from The Cancer Genome Atlas-colon adenocarcinoma and rectum adenocarcinoma projects were utilized. Mucinous and non-mucinous CRC were compared with regard to microsatellite status, overall mutation rate, the most frequently mutated genes, mutations in genes coding for mismatch repair (MMR) proteins and genes coding for mucin glycoproteins. CNA analysis and pathway analysis was undertaken. Mucinous CRC was more likely to be microsatellite instability-high (MSI-H) and hypermutated. When corrected for microsatellite status the single-nucleotide variation and insertion-deletion rate was similar between the two cohorts. Mucinous adenocarcinoma was more likely to have mutations in genes coding for MMR proteins and mucin glycoproteins. Pathway analysis revealed further differences between the two histological subtypes in the cell cycle, RTK-RAS, transforming growth factor-β, and TP53 pathways. Mucinous CRC has some distinct genomic aberrations when compared with non-mucinous adenocarcinoma, many of which are driven by the increased frequency of MSI-H tumors. These genomic aberrations may play an important part in the difference seen in response to treatment and prognosis in mucinous adenocarcinoma.


Anti-inflammatory effects of fimasartan via Akt, ERK, and NFκB pathways on astrocytes stimulated by hemolysate.
The aim of this study was to investigate whether fimasartan, a novel angiotensin II receptor blocker, modulates hemolysate-induced inflammation in astrocytes. We stimulated astrocytes with hemolysate to induce hemorrhagic inflammation in vitro. Astrocytes were pretreated with fimasartan and then incubated with hemolysate at different durations. Anti-inflammatory cell signaling molecules including Akt, extracellular signal regulated kinase (ERK), NFκB and cyclooxygenase-2 (COX-2) were assessed by western blotting. Pro-inflammatory mediators were evaluated by real-time RT-PCR and ELISA. The stimulation by hemolysate generated a robust activation of inflammatory signaling pathways in astrocytes. Hemolysate increased the phosphorylation of Akt at 1 h, and ERK1/2 at 20 min compared with the control group and promoted the degradation of IκBα. Pretreated fimasartan significantly decreased hemolysate-induced phosphorylation of Akt and ERK1/2. In addition, fimasartan also suppressed NFκB-related inflammatory pathways induced by hemolysate, including reduction of the gene expression of NFκB, and decreased nuclear translocation of NFκB and degradation of IκB. This reduction of inflammatory upstream pathways decreased the expression of inflammatory end-products: COX-2 and interleukin-1 (IL-1β). Furthermore, the expression of COX-2 was attenuated by both Akt inhibitor (LY294002) and ERK inhibitor (U0126), and IκBα degradation was suppressed by LY294002. These results demonstrate that pretreatment with fimasartan to astrocytes suppresses the inflammatory responses induced by hemolysate. Akt, ERK and NFκB were associated with hemolysate-induced COX-2 and IL-1β expression. Based on these mechanisms, fimasartan could be a candidate anti-inflammatory regulator for the treatment of intracerebral hemorrhage.


Inhibition of adenylate cyclase activity by polyamines in human erythrocyte plasma membranes.
Polyamines (spermidine, spermine and putrescine) inhibited the adenylate cyclase activity in a concentration dependent manner in human erythrocyte plasma membranes. Spermidine (Spd) exhibited more inhibitory effect than spermine (Spm) and putrescine (Put). On the contrary, the addition of amino acids (arginine, glutamine and lysine) did not influence the basal enzyme activity. Other cations (polylysine, polyarginine and polyglutamine) also did not affect the enzyme activity. Addition of all the three polyamines (Spd, Spm and Put) in the reaction mixture exhibited moderate inhibitory effect on the adenylate cyclase activity whether it was basal or activated with sodium fluoride or with forskolin. Since the three polyamines exhibited maximum inhibitory effect at 10 microM concentration which is within physiological limit for mammalian tissues, we suggest that there may be a regulatory function of these molecules on adenylate cyclase activity in human erythrocytes.


Recombinant expression of soluble murine prion protein for C-terminal modification.
Membrane attachment of prion protein (PrP) via its glycosylphosphatidylinositol (GPI) anchor plays a key role during conversion of cellular PrP(C) into its pathogenic isoform PrP(Sc). Strategies to access homogenous lipidated PrP via expressed protein ligation (EPL) are required to fully decipher the effect of membrane attachment. Such strategies suffer from insoluble expression of PrP-intein fusion constructs and low folding efficiencies that severely limit the available amount of homogeneous lipidated PrP. Here, we describe an alternative method for expression of soluble PrP-intein fusion proteins in Escherichia coli that provides access to natively folded PrP ready to use in EPL.


[The application of 3D geometric modular element for the removable partial denture].
To discuss the application way for element library of dentition and the removable partial denture. With the help of some software, such as PRO/E, POWERSHAPE, etc, design the content and structure of the element libraries reasonably, and discussed the efficiency way of usage. We can use the element libraries by the way of "import-edit",and the way of "element group". The structure of the element libraries is reasonable and can run effectively.


Effect of steatosis donor liver transplantation on hepatocellular carcinoma recurrence: experience at a single institution.
The increasing demand for transplantation has led application of steatotic liver as the graft. The aim of this study was to determine the effect of donor graft steatosis on overall outcome and tumor recurrence after liver transplantation for hepatocellular carcinoma. 131 patients that underwent liver transplantation for hepatocellular carcinoma between 2007 and 2008 were included. Donor steatosis was categorized as non-steatosis group (0%-10%, n=101) and steatosis group (>10%, n=30). The Kaplan-Meier method and Cox proportional hazard regression model was used for data analysis. Postoperative recipient survival rate was 81% and 66.6% at 1 and 3 years, respectively, for non-steatotic graft; 87.5% and 58.3% for mild steatosis; 83.3% and 41.7% for moderate to severe steatosis (p=0.303). Postoperative tumor recurrence rate was 15.8% and 28.7% at 1 and 3 years, respectively, for grafts with no steatosis; 8.3% and 20.8% for those with mild steatosis; 33.3% and 50% for those with moderate to severe steatosis, (p>0.05). Steatotic donor was not associated with a worse prognosis in early stage postoperative and mild fatty liver did not increase tumor recurrence risks. The moderate to severe status of fatty liver had some effect on tumor recurrence.


Observations on the effect of different methods of processing on the bacterial contaminants of bovine and ovine tripe.
A comparison was made of the multiplication of bacteria in specimens of tripe processed in different ways. There was little difference in this respect between commercial tripe as offered for purchase to the consumer and rough and scraped tripe incubated at 30 degrees C for 24 h. Tripe stored at 4 degrees C or in acetic acid (pH 4) at 30 degrees C for 24 h, however, had appreciably fewer bacteria.


Computed tomographic findings in subacute sclerosing panencephalitis.
We used a computed tomography to look for evidence of cerebral changes in a three-year-10-month-old girl with SSPE. The area of decreased density on CT corresponded to inflammatory and demyelinative lesions in the brain. CT scans seem to be a useful tool for more accurate assessment in the diagnosis of SSPE.


Enhanced dewaterability of waste activated sludge by UV assisted ZVI-PDS oxidation.
Ultraviolet (UV) assisted zero-valent iron (ZVI)-activated sodium persulfate (PDS) oxidation (UV-ZVI-PDS) was used to treat waste activated sludge (WAS) in this study. The dewaterability performance and mechanism of WAS dewatering were analyzed. The results showed that UV-ZVI-PDS can obtain better sludge dewatering performance in a wide pH range (2.0-8.0). When the molar ratio of ZVI/PDS was 0.6, UV was 254nm, PDS dosage was 200 mg/g TS (total solid), pH was 6.54, reaction time was 20 min, the CST (capillary suction time) and SRF (specific resistance to filtration) were decreased by 64.0% and 78.2%, respectively. The molar ratio of ZVI/PDS used in this paper is much lower than that of literatures, and the contents of total Fe and Fe2+ in sludge supernatant remained at a low level, as 3.7 mg/L and 0.0 mg/L. The analysis of extracellular polymeric substances (EPS), scanning electron microscope (SEM) and particle size distribution showed that the EPS could be effectively destroyed by UV-ZVI-PDS, the sludge flocs broken down into smaller particles, cracks and holes appeared, and then the bound water was released. At the same time, the highly hydrophilic tightly bound-EPS (TB-EPS) were converted into loosely bound EPS (LB-EPS) and soluble EPS (S-EPS). During sludge pretreated by UV-ZVI-PDS, positively charged ions, such as Fe2+, Fe3+ and H+, produced in the reaction system could reduce the electronegativity of sludge surface, promote sludge particles aggregation, and then enhanced the sludge dewaterability.


Action of nootropic drugs on transcallosal responses in rats.
The effects of nootropic drugs and related compounds on transcallosal responses were examined in urethane-anesthetized rats. The transcallosal response was recorded from the surface of the anterior neocortex following electrical stimulation of the contralateral corpus callosum. The transcallosal response consisted of a biphasic positive-negative waveform. Hopantenate increased the amplitude of the positive- and negative-waves, without affecting the latency. Aniracetam, idebenone, bifemelane hydrochloride, TRH and meclofenoxate increased the amplitude of the negative-wave, without affecting the latencies. Vinpocetine and eburunamonine had no effect on the transcallosal response. Muscimol, amino-oxyacetic acid, diazepam and pentobarbital increased the amplitude of the positive-wave and decreased the amplitude of the negative-wave, without affecting the latencies. Bicuculline and picrotoxin increased the amplitude of the negative-wave, without affecting the latencies. Physostigmine decreased the amplitude of the negative-wave, without affecting the latency. Atropine was without effect. The pharmacological nature of the transcallosal response is discussed, based on findings with 16 different pharmacological agents.


Identifying substance abuse in maltreating families: a child welfare challenge.
Studies of the link between parental substance abuse and child maltreatment suggest that chemical dependence is present in at least half of the families who come to the attention of child welfare authorities for child abuse and neglect. Parental substance abuse is thought to be a primary factor in greatly increased rates of children entering foster care over the past decade. It is also a clear risk factor for child mental health problems and poor developmental outcomes in children. At the same time, however, minimal attention is often given to training child protective services workers and other child welfare personnel in identifying and confronting substance abuse in families on their caseloads. The authors explore standardized methods developed for screening for substance abuse among various populations and suggest ways of adapting these screening devices for families reported for child maltreatment. They identify assessment and treatment considerations in substance abusing families as well.


NK cells and solid tumors: therapeutic potential and persisting obstacles.
Natural killer (NK) cells, which are innate lymphocytes endowed with potent cytotoxic activity, have recently attracted attention as potential anticancer therapeutics. While NK cells mediate encouraging responses in patients with leukemia, the therapeutic effects of NK cell infusion in patients with solid tumors are limited. Preclinical and clinical data suggest that the efficacy of NK cell infusion against solid malignancies is hampered by several factors including inadequate tumor infiltration and persistence/activation in the tumor microenvironment (TME). A number of metabolic features of the TME including hypoxia as well as elevated levels of adenosine, reactive oxygen species, and prostaglandins negatively affect NK cell activity. Moreover, cancer-associated fibroblasts, tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells actively suppress NK cell-dependent anticancer immunity. Here, we review the metabolic and cellular barriers that inhibit NK cells in solid neoplasms as we discuss potential strategies to circumvent such obstacles towards superior therapeutic activity.


Xenopus transcription factor IIIA binds primarily at junctions between double helical stems and internal loops in oocyte 5S RNA.
RNases and chemical probes were used to study the accessibility of each nucleotide of 5S RNA in the native and reconstituted 7S particle from Xenopus laevis oocytes. RNase or chemically treated 5S RNA from intact 7S particles was isolated and analysed using an oligodeoxynucleotide primer and reverse transcriptase. The results were superimposed on a cylindrical projection of an RNA double helix and the protection effects were shown to cluster at two regions on the molecular surface. A three-dimensional model is proposed for the 7S particle in which protein-RNA contacts occur mainly in the major groove of 5S RNA.


The reperfusion era. Strategies for establishing or maintaining coronary patency.
Only 3 decades ago, controversy existed over the origin of the thrombus that occluded coronary arteries during myocardial infarction (MI). Then, the acute clinical angiographic studies of DeWood butterssed new pathological and experimental evidence that the thrombus was the proximate cause of MI and unstable angina. The remaining years of the 20th century saw an explosion of knowledge delineating a spectrum of related disorders now collectively called acute coronary syndromes (ACS). The clinician managing patients is confronted with an array of evidence as more than 75,000 patients worldwide have been randomized to clinical trials in ACS. This article reviews key pathophysiological concepts, presents an initial strategy for triage of patients, and summarizes evidence-based medicine guiding therapy for acute coronary lesions.


"A peer support worker can really be there supporting the youth throughout the whole process": a qualitative study exploring the role of peer support in providing substance use services to youth.
Youth (ages 12-24) rarely access services and supports to address substance use concerns. Peer support can facilitate service engagement and has been associated with positive substance use recovery outcomes in adults, yet few studies have examined this role among youth specifically. As such, this qualitative study explored the role of peer support in providing substance use services to youth in British Columbia and how best to support them in their role. Participatory action research methods were used by partnering with youth who had lived/living experience of substance use, including peer support workers, to co-design the research protocol and materials. An initial focus group and subsequent interviews were held with 18 peer support workers who provide services to youth (ages 12-24) based on their own lived experience with mental health and/or substance use. The discussions were audio-recorded, transcribed verbatim, and analysed thematically using an inductive approach. Peer support workers' core experiences providing substance use services to youth centred around supporting youth throughout the whole process. This was accomplished by meeting youth where they are at, providing individualized care, and bridging the gap between other services and supports. However, participants experienced multiple organizational barriers hindering their ability to support youth and stressed the importance of having an employer who understands the work you are doing. This involved having someone advocating for the peer support role to promote collaboration, empowering peers to set boundaries and define their own role, and providing adequate training and mentorship. Finally, peer support workers described how their lived experience bridges connection and de-stigmatization at the individual, organizational, and community level, which was unique to their role. Peer support plays a unique role in youths' substance use journeys, given their own lived experience and flexibility within their role. However, their position is often misunderstood by employers and other service providers, leaving peers with inadequate support, training, and mentorship to do their job. The findings from this study call for improved integration of peer support into service environments, as well as standardized training that is in-depth and continuous.


Intimacy--meeting needs and respecting privacy in the care of elderly people: what is a good moral attitude on the part of the nurse/carer?
This article explores notions of intimacy in the caring context. The aspects discussed are: privacy and intimacy; intimacy as emotional and/or physical closeness; intimacy as touch; sexual intimacy and normal ageing; sexual intimacy and patients suffering from dementia; and intimacy as trust. Examples are given and problems are identified, with reflection on the attitude and behaviour of the carer. It is suggested that when trying to make moral decisions in concrete situations it is imperative that the carer is aware of the values upon which his or her own thinking is based. It is argued that the guiding principle should be the moral assumption that the carer's responsibility can never be interpreted as a right to disregard the wishes of the patient. Hence, the key word in daily care is 'respect'.


Fractionated total body irradiation and allogeneic bone marrow transplantation for standard risk leukemia.
From March 1982 to December 1986, 32 patients with standard risk leukaemia were conditioned for allogeneic bone marrow transplantation (BMT) with low dose fractionated total body irradiation (TBI) after infusion of alkylating agents. This series includes six children and 26 adults. Minimal follow-up was 24 months. The total dose of 11 Gy, given in 5 daily fractions of 2.20 Gy, was given in the lateral position, following chemotherapy with either melphalan or cyclophosphamide. Lungs were shielded for 2 out of the 5 fractions. All patients had in vivo dosimetry. The death rate is 25% without relapse or rejection. Disease-free survival is 73% at 5 years. Toxic deaths are detailed: 2 from sepsis and veino-occlusive disease of the liver, 3 from severe graft versus host disease (GVHD), 2 from GVHD associated with virus pneumonitis and one from HIV infection. Fractionated low dose rate TBI is discussed regarding its decreased toxicity and its efficiency for disease control.


Characteristics of an isolated greater tuberosity fracture of the humerus.
Most classification systems tend to include isolated greater tuberosity fractures in the group of proximal humeral fractures. The purpose of this study was to elucidate demographic differences between isolated greater tuberosity fractures and the other proximal humeral fractures. Altogether, 610 proximal humeral fractures were divided into isolated greater tuberosity fractures of the proximal humerus (group I) and all other proximal humeral fractures (group II). The two groups were analyzed according to their incidence, age and sex distribution, presence of dislocation, and associated chronic medical problems. Group I comprised 18.9% and group II 81.1% off all fractures. The mean age of group I was 42.8 years, and that of group II was 54.2 years. Of the 115 (67.8%) patients in group I, 78 (67.8%) were male. In contrast, most of the group II patients were female (332/495, 67.1%). A higher incidence of glenohumeral dislocation occurred in group I (6.9%) than in group II (3.4%). Of the 495 group II patients, 175 (35.4%) had medical problems, including endocrine, cardiovascular, pulmonary, hepatic, and renal disease, whereas only 15 of the 115 (13%) patients in group I had such problems. Patients with isolated greater tuberosity fractures of the proximal humerus were different demographically, and their treatment and classification should be considered separately from that for other proximal humeral fractures.


Sodium and large arteries in hypertension. Effects of indapamide.
Epidemiologic studies evaluating arterial pulse wave velocity together with blood pressure indicate that: (1) salt intake has an independent effect on arteriolar tone and arterial wall properties, with the former indirectly and the latter directly contributing to increased arterial stiffness with age; and (2) normotensive adult subjects who follow a low sodium diet have reduced arterial stiffness and this effect is independent of blood pressure. Conversely, in elderly persons with isolated systolic hypertension, isotonic saline infusion causes a predominant increase in systolic pressure due to an increase in the stiffness of the arterial wall. The diuretic indapamide produces a decrease in blood pressure without significant change in brachial artery diameter. The result indicates a shift of the pressure-diameter curve, reflecting for the first time in humans a pharmacologic effect of the drug on arterial vessel. Furthermore, diuretic drugs may increase arterial distensibility and compliance in hypertensive patients, but this effect seems to be more pronounced in older than in younger subjects. In the latter, either activation of the sympathetic nervous system or potassium depletion, or both, might counteract the improvement in arterial distensibility caused by blood pressure reduction and sodium depletion. Based on epidemiologic, clinical, and pharmacologic studies, this critical review suggests that, in patients with essential hypertension, changes of sodium intake in diet or administration of diuretics, or both, affect the status of large arteries independently of blood pressure changes.


A longitudinal study on postoperative hearing thresholds with the Vibrant Soundbridge device.
The Vibrant Soundbridge is a semi-implantable middle ear hearing device used in the rehabilitation of adults with sensorineural hearing loss. In order to evaluate the long-term effects of the implanted part of the device, audiological data from 39 patients implanted over several implant sites across France were collected and analyzed retrospectively. The mean follow-up time was 16 months; 25 patients had a follow-up period of over 1 year. Surgery was uneventful in all cases. The present study of the 39 implanted patients with a mid- to long-term follow-up found a statistically significant modification of hearing thresholds (pre- versus postoperative) for frequencies of 0.5 and 4 kHz. However, the shift of threshold was rather limited (2.79 and 3.34 dB, respectively), and this variation was not statistically different from the evolution of the opposite non-operated ear.


Gender-Related and Age-Related Differences in Implantable Defibrillator Recipients: Results From the Pacemaker and Implantable Defibrillator Leads Survival Study ("PAIDLESS").
The purpose of this study was to investigate the influences of gender and age on defibrillator lead failure and patient mortality. The specific influences of gender and age on defibrillator lead failure have not previously been investigated. This study analyzed the differences in gender and age in relation to defibrillator lead failure and mortality of patients in the Pacemaker and Implantable Defibrillator Leads Survival Study ("PAIDLESS"). PAIDLESS includes all patients at Winthrop University Hospital who underwent defibrillator lead implantation between February 1, 1996 and December 31, 2011. Male and female patients were compared within each age decile, beginning at 15 years old, to analyze lead failure and patient mortality. Statistical analyses were performed using Wilcoxon rank-sum test, Fisher's exact test, Kaplan-Meier analysis, and multivariable Cox regression models. P<.05 was considered statistically significant. No correction for multiple comparisons was performed for the subgroup analyses. A total of 3802 patients (2812 men and 990 women) were included in the analysis. The mean age was 70 ± 13 years (range, 15-94 years). Kaplan-Meier analysis found that between 45 and 54 years of age, leads implanted in women failed significantly faster than in men (P=.03). Multivariable Cox regression models were built to validate this finding, and they confirmed that male gender was an independent protective factor of lead failure in the 45 to 54 years group (for male gender: HR, 0.37; 95% confidence interval, 0.14-0.96; P=.04). Lead survival time for women in this age group was 13.4 years (standard error, 0.6), while leads implanted in men of this age group survived 14.7 years (standard error, 0.3). Although there were significant differences in lead failure, no differences in mortality between the genders were found for any ages or within each decile. This study is the first to compare defibrillator lead failure and patient mortality in relation to gender and age deciles at a single large implanting center. Within the 45 to 54 years group, leads implanted in women failed faster than in men. Male gender was found to be an independent protective factor in lead survival. This study emphasizes the complex interplay between gender and age with respect to implantable defibrillator lead failure and mortality.


Formation of M1G-dR from endogenous and exogenous ROS-inducing chemicals.
The present study provides fundamental information regarding the production of M1G-dR by ROS. To investigate the production of M1G-dR from deoxyribose damage as caused by ROS, calf thymus DNA (CT-DNA) was incubated with NAD(P)H, CuCl2, and various concentrations of hydrogen peroxide (H2O2). The incubation of CT-DNA with H2O2 resulted in concentration-dependent increases in the number of M1G-dR adducts. In subsequent experiments, 1,4-tetrachlorobenzoquinone or catechol estrogens were evaluated for their effects on M1G-dR formation. In addition, the role of lipid peroxidation in the formation of M1G-dR was verified using an in vitro lipid peroxidation model which consisted of methyl esters of either fish oil or purified fatty acids found in cellular membranes. This experiment confirmed that M1G-dR is a major DNA adduct produced by lipid peroxidation. Furthermore, the number of double bonds in polyunsaturated fatty acids was found to be the key factor in the formation of M1G-dR. The findings obtained from this study provide important information regarding the molecular pathways for M1G-dR formation by ROS, which is an essential element in understanding and evaluating the genotoxicity of a variety of ROS-inducing chemicals.


A study on specific factors related to inflammation and autophagy in BEAS-2B cells induced by urban particulate matter (PM, 1648a) and histological evaluation of PM-induced bronchial asthma model in mice.
As particulate matter (PM) poses an increasing risk, research on its correlation with diseases is active. However, researchers often use their own PM, making it difficult to determine its components. To address this, we investigated the effects of PM with known constituents on BEAS-2B cells, examining cytokine levels, reactive oxygen species ROS production, DNA damage, and MAPK phosphorylation. Additionally, we evaluated the effects of PM on normal and OVA-induced asthmatic mice by measuring organ weight, cytokine levels, and inflammatory cells in bronchoalveolar lavage fluid, and examining histological changes. PM markedly increased levels of IL-6, GM-CSF, TNF-α, ROS, nitric oxide, and DNA damage, while surprisingly reducing IL-8 and MCP-1. Moreover, PM increased MAPK phosphorylation and inhibited mTOR and AKT phosphorylation. In vivo, lung and spleen weights, IgE, OVA-specific IgE, IL-4, IL-13, total cells, macrophages, lymphocytes, mucus generation, and LC3II were higher in the asthma group. PM treatment in asthmatic mice increased lung weight and macrophage infiltration, but decreased IL-4 and IL-13 in BALF. Meanwhile, PM treatment in the Nor group increased total cells, macrophages, lymphocytes, and mucus generation. Our study suggests that PM may induce and exacerbate lung disease by causing immune imbalance via the MAPK and autophagy pathways, resulting in decreased lung function due to increased smooth muscle thickness and mucus generation.


Improving the E coding of hospitalizations for injury: do hospital records contain adequate documentation?
Incomplete external cause of injury (E) coding limits the usefulness of hospital discharge data sets for injury surveillance and research. Hospital medical records were examined to determine whether they contained adequate cause of injury documentation to allow for more complete E coding of injury discharges. Medical records for a sample of discharges involving a principal diagnosis of injury from the Uniform Hospital Discharge Data Set for Rhode Island were selected. We assigned E codes to these discharges and compared our E codes with those of the discharge data set. Documentation of cause of injury in the medical records was sufficient to allow assignment of a specific E code to 70% of the injuries for which no E codes or vague E codes were submitted on the Uniform Hospital Discharge Data Set. It was estimated that specific cause of injury documentation is available in the medical records of 80% of all injury discharges in Rhode Island; for approximately 90%, an E code describing at least the broad cause of injury could be assigned. Rates of E coding can be substantially increased by making better use of existing documentation in medical records.


Partial trisomy of the long arm of chromosome 1 due to a familial translocation t(1;10) (q32;q26).
A new case of partial trisomy for the long arm of chromosome 1 was observed in a newborn female, who died at age 26 days. The father was a proven carrier of a balanced translocation involving chromosomes 1 and 10.


Management of osteoradionecrosis of the jaws: an analysis of evidence.
To review and discuss the management of jaw bone osteoradionecrosis (JORN) based on levels of evidence. The Medline/PUBMED and Cochrane search was performed to identify all studies on the management of JORN, published in English, French, and German during January 1975-October 2007. Only clinical researches were identified and classified into four levels of evidence before being examined. All references of the retrieved articles were analysed. Seventy three articles and their additional 45 citations were evaluated. Most of the eligible literature provided observational evidence. Hyperbaric oxygen therapy (HBOT) is an adjunct; however, its clinical usefulness remains controversial. A conservative approach should be limited to early-onset JORN, while radical surgery is indicated for an advanced or refractory lesion. Free tissue transfer is the reconstruction of choice for large defects without the need of HBOT. Some new technologies have also been studied, including ultrasound, biological molecules, distraction osteogenesis and antioxidant agents. Most of the reports on the treatment of JORN offer weak evidence. Current information seems insufficient for establishing the definite treatment guideline; thus, well-designed studies with long-term clinical data are encouraged.


E/P-selectin-deficient mice: an optimal mutation for abrogating antigen but not tumor necrosis factor-alpha-induced immune responses.
Leukocyte recruitment in cremaster microcirculation was visualized by intravital microscopy, either in ovalbumin sensitized and challenged animals, or in response to TNF-alpha. In antigen-challenged mice a significant increase in leukocyte rolling (approximately 50 to 200-300 cells/min) and adhesion (2 to 15-20 cells/100 microm), and a very dramatic increase in emigration ( approximately 1 to >40 cells/field) was observed over 24 h. Although rolling and adhesion was dramatically blunted in P-selectin- or P selectin/ICAM-1-deficient mice, emigrated cell number was similar to that observed in wild-type mice. Leukocyte rolling, adhesion and emigration was almost entirely abrogated over 24 h in E/P-selectin-deficient mice, demonstrating that antigen-induced leukocyte recruitment can be entirely disrupted in the absence of both endothelial selectins. However, E/P-selectin-deficient mice were able to recruit leukocytes at 24 h after TNF-alpha challenge. Rolling 24 h post-TNF-alpha in E/P-selectin-deficient mice was not inhibitable with anti-L-selectin antibody, suggesting an entirely selectin-independent pathway of rolling. We identified this pathway to be alpha (4)-integrin dependent and demonstrated that VCAM-1 expression was increased only in mice challenged with TNF-alpha. These data demonstrate that, in vivo, sufficient amounts of TNF-alpha can recruit leukocytes independently of selectins, whereas inhibition of endothelial selectins is the optimal intervention in reducing the immune response to antigen.


Enzyme-linked immunosorbent assay for the human glial fibrillary acidic protein using a mouse monoclonal antibody.
Two enzyme-linked immunosorbent assays (ELISAs) have been developed for the quantification of soluble human glial fibrillary acidic protein (GFAP). The specificity of the assays for GFAP is ensured by the use of a monoclonal antibody directed against a GFAP-specific antigenic determinant. One ELISA is a four-layer system working in the concentration range 5-600 ng GFAP/ml. The other ELISA is a five-layer system and includes a biotin/avidin binding reaction. The latter assay has a working range of 0.5-60 ng GFAP/ml. The assays may be used for quantification of GFAP in CSFs, amniotic fluids, and extracts or homogenates of normal and pathological brain material. GFAP in serum could not be quantified because of unidentified interference. CSFs from 18 nonneurological subjects were found to contain 2-14 ng GFAP/ml (mean 4.1 ng/ml), whereas amniotic fluids from 50 normal pregnant women contained up to 24 ng GFAP/ml (mean 12.4 ng/ml). GFAP concentrations in CSFs from 32 multiple sclerosis patients were found not to be elevated compared to the control group.


Peripheral nervous system in a case of canine giant axonal neuropathy.
The pathology of the peripheral nerves in a dog with naturally occurring giant axonal neuropathy (GAN) is described. Axonal swellings were found predominantly in the distal portions of the tibial and recurrent laryngeal nerves. Excess neurofilaments, often arranged in whorls, were present in the swellings which were found in both myelinated and non-myelinated fibres. Other axonal organelles tended to be isolated in small pockets and on occasions adaxonal Schwann cell processes partially separated these organelles from the axoplasm. The myelin sheath was attenuated over the swellings and short lengths of demyelinated axon were often seen adjacent to the enlargements. Some Schwann cells also contained excessive microfilaments. The peripheral nerve pathology in the dog appear closely similar to that of human GAN and to certain experimental toxic neuropathies, particularly those produced by n-hexane and methyl-butyl ketone.


When Indian crabs were not yet Asian--biogeographic evidence for Eocene proximity of India and Southeast Asia.
The faunal and floral relationship of northward-drifting India with its neighboring continents is of general biogeographic interest as an important driver of regional biodiversity. However, direct biogeographic connectivity of India and Southeast Asia during the Cenozoic remains largely unexplored. We investigate timing, direction and mechanisms of faunal exchange between India and Southeast Asia, based on a molecular phylogeny, molecular clock-derived time estimates and biogeographic reconstructions of the Asian freshwater crab family Gecarcinucidae. Although the Gecarcinucidae are not an element of an ancient Gondwana fauna, their subfamily Gecarcinucinae, and probably also the Liotelphusinae, evolved on the Indian Subcontinent and subsequently dispersed to Southeast Asia. Estimated by a model testing approach, this dispersal event took place during the Middle Eocene, and thus before the final collision of India and the Tibet-part of Eurasia. We postulate that the India and Southeast Asia were close enough for exchange of freshwater organisms during the Middle Eocene, before the final Indian-Eurasian collision. Our data support geological models that assume the Indian plate having tracked along Southeast Asia during its move northwards.


Keto leucine and keto isoleucine are bioavailable precursors of their respective amino acids in cell culture media.
Highly concentrated cell culture media formulations are essential to develop next generation bioprocesses used to produce therapeutic monoclonal antibodies, fusion proteins, bispecific molecules and mAb fragments. Although cysteine/cystine and tyrosine are the first components preventing the development of highly concentrated complex cell culture media, leucine and isoleucine were identified as the next critical amino acids due to their limited solubility. This work sought to investigate highly soluble and readily bioavailable derivatives of both amino acids that may be used in batch, fed-batch or perfusion processes. The α-keto acids of Leu and Ile, keto leucine and keto isoleucine sodium salts, were tested in cell culture media and proved to be beneficial to increase the overall solubility of cell culture media formulations. These keto acids were readily bioavailable for various CHO cells and can be used in both media and feeds. The quality of the final recombinant protein was studied in processes using the precursors and the mechanism of amination was investigated in CHO cells. Altogether, both keto acids represent an alternative to their respective amino acids to develop highly concentrated cell culture media formulations to support next generation bioprocesses.


Management of congenital nasolacrimal duct obstruction in down syndrome.
Congenital nasolacrimal duct obstruction (CNLDO) is common in Down Syndrome (DS), and more difficult to treat. Our purpose was to describe the management of CNLDO in paediatric patients with DS. Retrospective cohort study. Medical chart review of all DS patients diagnosed with CNLDO at the Division of Ophthalmology at the Children's Hospital of Philadelphia during a 12-year period (2009-2020). Main outcome measures included: Surgical interventions, primary probing outcome, rate of dacryocystorhinostomy (DCR) and/or conjunctivodacryocystorhinostomy (CDCR), and overall success. 126 patients (236 eyes) were included, mean age of 1.8 ± 2.1 years (range 0.1-11.3 y), 110 (87%) had bilateral CNLDO. Mean follow-up time was 41 months. 84 patients (67%) underwent at least one surgical intervention; the mean number of surgical interventions in this group was 1.8 ± 1.4 per patient (range, 1-6). The most common primary intervention was probing (n = 74, 88%), mostly (n = 57, 68%) with monocanalicular silicone intubation. Probing with silicone intubation had a higher success rate compared to probing alone (P = 0.002). Twenty (24% of 84) patients underwent DCR/CDCR during the follow-up period. Complete resolution was achieved in 123 patients (98%). CNLDO in Down syndrome is associated with high rates of bilateral obstructions and with less favourable surgical outcomes. Many patients ultimately require a more robust surgical intervention such as DCR or CDCR. The use of monocanalicular stent in initial probing was associated with a higher success rate, and would appear to be appropriate in all CNLDO-DS cases.


Association and decontamination of Bacillus spores in a simulated drinking water system.
The objective of this work was to elucidate the disinfectant susceptibility of Bacillus anthracis Sterne (BA) and a commercial preparation of Bacillus thuringiensis (BT) spores associated with a simulated drinking water system. Biofilms composed of indigenous water system bacteria were accumulated on copper and polyvinyl chloride (PVC) pipe material surfaces in a low-flow pipe loop and uniformly mixed tank reactor (CDC biofilm reactor). Application of a distributed shear during spore contact resulted in approximately a 1.0 and 1.6 log10 increase in the number of spores associated with copper and PVC surfaces, respectively. Decontamination of spores in both free suspension and after association with biofilm-conditioned pipe materials was attempted using free chlorine and monochloramine. Associated spores required 5- to 10-fold higher disinfectant concentrations to observe the same reduction of viable spores as in suspension. High disinfectant concentrations (103 mg/L free chlorine and 49 mg/L monochloramine) yielded less than a 2-log10 reduction in viable associated spores after 60 min. Spores associated with biofilms on copper surfaces consistently yielded higher Ct values than PVC.


Isolation and identification of some urinary inhibitors of calcium phosphate formation.
Normal urine has been examined for substances which inhibit formation of calcium phosphate. A separation scheme involving ultrafiltration, precipitation, electrophoresis and paper chromatography was devised to isolate these substances. Contrary to what has been suggested in the literature for many years, the urines examined did not contain a potent unidentified inhibitor. The major anionic inhibitors were citric acid, pyrophosphate and isocitric acid. These substances together with a small contribution from the cations appeared to account for most, if not all, of the inhibitory activity of urine.


The effects of aging on early stages of the auditory deviance detection system.
The aging effects on auditory change detection have been studied using the Mismatch Negativity (MMN) potential. However, recent studies have found earlier correlates of deviance detection at the level of the middle-latency response (MLR) and the effects of aging on this deviant-related response have not yet been clarified. The purpose of this study was to examine the effects of aging on both levels of the auditory deviance detection system. MMN and MLR responses were recorded in 33 young and 29 older adults from 32 scalp electrodes during frequency oddball and swapped-oddball conditions. In the young group, modulation of MLR and a clear MMN response were observed, whereas in the aged group, no evidence of deviance detection was found at the level of MLR and the MMN amplitude was significantly diminished. Based on the obtained results, aging affects both levels of the auditory deviance detection system which seems to be a result of deficits in regularity encoding along the auditory hierarchy. The current findings suggest that age-related physiological changes result in deficits in regularity encoding, starting from early stages of processing. This might eventually affect stream segregation and induce difficulties in understanding speech in complex environments.


Strategies to Reduce Long-Term Drug Resistance by Considering Effects of Differential Selective Treatments.
Despite great advances in modeling and cancer therapy using optimal control theory, tumor heterogeneity and drug resistance are major obstacles in cancer treatments. Since recent biological studies demonstrated the evidence of tumor heterogeneity and assessed potential biological and clinical implications, tumor heterogeneity should be taken into account in the optimal control problem to improve treatment strategies. Here, first we study the effects of two different treatment strategies (i.e., symmetric and asymmetric) in a minimal two-population model to examine the long-term effects of these treatment methods on the system. Second, by considering tumor adaptation to treatment as a factor of the cost function, the optimal treatment strategy is derived. Numerical examples show that optimal treatment decreases tumor burden for the long-term by decreasing rate of tumor adaptation over time.


Incidental melanomas detected in veterans referred to dermatology.
Early detection of melanoma is integral to preventing morbidity and mortality. We sought to characterize and compare incidental versus consult melanomas detected in veterans referred to the Minneapolis, MN, Department of Veterans Affairs Medical Center dermatology clinic. We retrospectively reviewed charts of all dermatology consults between January 2004 and March 2012. Of the 28,405 consults sent during the study period, 17,174 met inclusion criteria. There were 231 melanomas identified in 221 patients. In all, 144 melanomas were identified on the consult and 87 melanomas were discovered incidentally. The incidental melanoma detection rate was 0.5% (84/17,174). Consult melanomas were more likely to be invasive than incidental melanomas (relative risk 1.51, 95% confidence interval 1.23-1.86, P < .0001) and less likely to have a Breslow depth of less than 1.00 mm (relative risk 0.73, 95% confidence interval 0.61-0.88, P = .0036). Incidental melanomas were smaller than consult melanomas (mean diameter 0.98 vs 1.3 cm, respectively) and thinner (mean Breslow depth 0.64 vs 1.74 mm). Consult melanomas were more likely to be detected on the head/neck (relative risk 1.25, 95% confidence interval 1.03-1.52, P = .0295). Nondiverse patient population is a limitation. Melanomas detected during an in-person skin examination by a dermatologist were more likely to be detected at an earlier stage of disease.


Emergency Department staff experiences of screening and response for intimate partner violence in a multi-site feasibility study: Acceptability, enablers and barriers.
Intimate partner violence is a lead cause of ill health and premature death among Australian women. Abused women are likely to present to Emergency Departments. Routine screening provides opportunities to identify and respond to intimate partner violence. A six-month screening feasibility study was conducted in two rural and one urban NSW Emergency Departments. Surveys with participating nurses, medical officers and social workers, as well as focus groups with nurses and social workers were conducted at each site to understand their experience. Survey respondents (n = 198) agreed it was appropriate (87%) and acceptable (91%) to screen for intimate partner violence in Emergency Departments. Overall 62% of respondents suggested screening had positive impacts on womens' care. Focus group discussions with 39 nurses and social workers identified enablers of screening as: ease of use of the screening tool; availability of social work response within one hour (as per the study protocol); and executive support. Barriers were: high patient volume; lack of integration with existing processes; lack of privacy and brevity of training. Screening in Emergency Departments was strongly supported by health practitioners who responded to the survey. Work is needed to address competing demands, integration of screening processes, and staff training.


The laboratory school protocol: its origin, use, and new applications.
ADHD is the most common childhood psychiatric disorder, with impairments seen in home and academic settings. To investigate such impairments in a school-like setting, the laboratory school protocol (LSP) was developed at the University of California, Irvine. This model provides a rigorously controlled environment to examine pharmacodynamic and pharmacokinetic aspects of responses to treatment. A key principle of this methodology is to exercise tight control of the timing and context of measurements by establishing a cycle of activities repeated across each study day. In addition, the LSP approach has been extended to both younger and older populations than the typically studied school-aged group. This extension requires corresponding modifications in measures to characterize drug efficacy and to allow evaluation of ADHD symptoms in a highly standardized setting. This article provides guidelines for employing the LSP for the assessment of medication effects for both preschool and adolescent/adult populations. The LSP can be modified to form either an Adult Workplace Environment or a Preschool Assessment Laboratory.


Subjective reports of withdrawal among cocaine users: recommendations for DSM-IV.
The proposed DSM-IV criteria for substance use disorders have included, as an option, a subtyping for physiologic dependence, characterized by either tolerance or withdrawal. Even if this option is not chosen at this stage of system revision, this weighting scheme justifies wider surveillance of these symptoms, especially for the more newly described cocaine dependence disorder. Wider surveillance of withdrawal is possible with the CIDI Substance Abuse Module (SAM), a WHO/ADAMHA diagnostic interview which covers criteria of substance use disorders according to the DSM-III, III-R, ICD-10 and proposed DSM-IV systems. To aid in this effort, we used the SAM, which includes a master list of all symptoms (n = 16) in the DSM manuals related to withdrawal from any substance to assess withdrawal symptoms from all substances. In this study, we hypothesized that the persons who used opiates with cocaine might misattribute their symptoms to cocaine; thus, we compared the responses of persons who used cocaine and opiates (opiate users) with the responses of persons who used cocaine without opiates (non-opiate users). Data from two St. Louis studies were combined for these analyses, users not in treatment or newly enrolled to drug-free or methadone treatment from a NIDA demonstration project and users selected for the St. Louis DSM-IV Field Trial. Of the 196 persons included from the field trial, 80% reported lifetime cocaine use compared with 91% of the 412 persons from the demonstration project. The symptoms mentioned in the diagnostic manuals were among the most frequently endorsed by both cocaine use groups.(ABSTRACT TRUNCATED AT 250 WORDS)


cDNA-AFLP-based transcript profiling for genome-wide expression analysis of jasmonate-treated plants and plant cultures.
cDNA-AFLP is a commonly used, robust, and reproducible tool for genome-wide expression analysis in any species, without requirement of prior sequence knowledge. Quantitative expression data are generated by gel-based visualization of cDNA-AFLP fingerprints obtained by selective PCR amplification of subsets of restriction fragments from a double-stranded cDNA template. Differences in gene expression levels across the samples are reflected in different band intensities on the high-resolution polyacrylamide gels. The differentially expressed genes can be identified by direct sequencing of re-amplified cDNA-AFLP tags purified from the gels. The cDNA-AFLP technique is especially useful for profiling of transcriptional responses of jasmonate-treated plants or plant (tissue) cultures and the discovery of jasmonate-responsive genes.


Toxicity in animals. Trends in evolution?
Animals acquire toxicity either by metabolic synthesis of toxins (secondary metabolites), by expression of toxin genes or by the uptake, storage and sequestration of toxins produced by other organisms, i.e., microbes, plants or other animals. Variability of toxin structure and function is high. Peptide toxins in particular, although relying on a limited number of structural frameworks, often exhibit considerable structural hypervariability. An accelerated rate of evolution in the toxin gene structure (conserved introns, but high substitution rates in the exons) leads to the functional diversity of these peptides or proteins. The selective forces which may drive toxin evolution are unknown. Venomousness or the possession of toxins can be essential for survival, but the advantage of toxin biosynthesis may also be of minor importance or has been lost during evolution.


Introduction.
Establishment and maintenance of pregnancy in a number of mammalian species depends upon a tightly regulated interaction between the semiallogeneic conceptus and the maternal uterine endometrium.The term "Maternal Recognition of Pregnancy" is attributed to Roger V. Short's paper titled "Implantation and the Maternal Recognition of Pregnancy" which was published in proceedings from the 1969 Symposium on Foetal Autonomy.Professor Short's landmark paper stimulated increased interest in elucidating how the conceptus signals its presence to assure maintenance of the corpus luteum beyond the normal length of the estrous or menstrual cycle to allow pregnancy to be established and maintained.Ten years following publication of Professor Short's paper, a Ciba Foundation Symposium entitled "Maternal Recognition of Pregnancy" brought together leading scientists to discuss the multiple mechanisms and pathways by which different viviparous species establish a successful pregnancy.The present volume on "Regulation of Implantation and Establishment of Pregnancy in Mammals" brings together current reviews from leading experts to address the diversity of mechanisms by which species establish and maintain pregnancy.Implantation in mice, dogs, pigs, cattle, sheep, horses, primates, humans and species in which embryonic diapause occurs are discussed.Reviews will provide current knowledge on the role of endometrial steroid receptors, adhesion factors, cytokines, interferons, steroids, prostaglandins, growth factors and immune cells involved with regulation of conceptus development.


Advanced age in horses affects divisional history of T cells and inflammatory cytokine production.
A number of model systems have been employed to investigate age-associated changes in immune function. The purpose of the current study was to characterize senescent T cells and to investigate the inflamm-aging phenomenon both in vitro and in vivo using the old horse as a model. We examined whether decreased T cell proliferation induced by Con A is caused by increased apoptosis. We also utilized intracellular CFSE to analyze changes within each round of cell proliferation, in particular cytokine production. Intracellular staining with flow cytometry, RT-PCR, and ELISA were used to measure pro-inflammatory cytokines both in vitro and in vivo. While lymphocytes from old horses exhibit decreased proliferation, this is not the result of increased apoptosis. Instead, a larger percentage of the T cells remain in the parent generation and produce significant amounts of IFNgamma. Likewise, old horses have increased frequency of CD8-IFNgamma+ T cells and TNFalpha producing cells. We also show that old horses have elevated levels of IL-1beta, IL-15, IL-18 and TNFalpha gene expression in peripheral blood and significant levels of TNFalpha protein in serum, all characteristics of inflamm-aging.


Making waves: Applying systems biology principles in water distribution systems engineering.
The complexity of modeling water quality variations in water distribution systems (WDS), studied for decades, stems from multiple constraints and variables involved and the complexity of the system behavior. The conventional macroscale-based WDS water quality models are founded on continuum mechanics. In attempts to provide a broad picture of the multi-species interactions, these models overlook the stochasticity corresponding to the reaction mechanisms within the WDS domain. Furthermore, owing to the black-box type modeling adopted in simulating the multi-species interactions, the existing state-of-the-art models have limitations in representing intermediates and/or by-products formation. Accordingly, they remain ineffective in describing the water chemistry-stoichiometric interactions within the WDS domain. Only a radically new modeling approach could overcome the limitations of the macroscale-based approaches and enables analyzing the stochastic WDS mechanisms by keeping the true nature of the system behavior. Stimulated by the metabolic network modeling principles in systems biology, this article outlines the prospect of developing an innovative 'water'bolic network modeling approach to provide a new outlook to the existing WDS water quality modeling research.


Modified resolution factor for asymmetrical peaks in chromatographic separation.
The quality of separation is measured by resolution factor (R(s)) between adjacent peaks. The current United States Pharmacopeia (USP) method for R(s) calculation assumes symmetrical peak shapes. In practice, perfectly symmetrical peaks are rarely encountered. The goal of this study was to correct the inaccuracy due to peak asymmetry by using a new formula for R(s) calculation. Peak tailing factor was incorporated into the formula for the calculation of R(s) to correct for the peak asymmetry. The resulting modified formula was compared with USP formula using simulated peaks and actual peaks. Through mathematical derivation, the modified R(s) was expressed as: R=[2(t(2)+W(2)/2(1-1/TF(2))-t(1)-W(1)/2(1-1/TF(1)))]/W(1)+W(2) where t(1) and t(2) are the retention times of two peaks, W(1) and W(2) are peak widths at baseline, TF(1) and TF(2) are USP tailing factors. All parameters used in the formula are available from commercial data analysis software. Comparisons of modified R(s) to USP R(s) showed that the modified R(s) provided a more accurate measure of peak separation at the baseline level.