In vitro and in vivo induction of squamous cell carcinoma antigen (SCC) in a uterine cervical cancer cell line (SKG-IIIa) with peplomycin and sodium butyrate.
In order to investigate the effect of an antisquamous cell carcinoma drug, peplomycin, the new analogue of bleomycin, on the production of a squamous cell carcinoma-associated tumor marker termed "SCC" (or TA-4), we carried out in vitro and in vivo experiments using the uterine cervical epidermoid cancer cell line SKG-IIIa, together with the investigation of the effect of sodium butyrate which was reported to be one of the representative gene modulators. In vitro production of SCC was biochemically and immunocytochemically confirmed in SKG-IIIa cells. Immunocytochemistry using anti-SCC antibody revealed that the total number of SCC-positive cells increased after the treatment with peplomycin (1.6 fold) or sodium butyrate (1.5 fold). The total amount of SCC in cultured medium, intracellular SCC, and cell debris during 5 days of culturation also increased with peplomycin (1.8 fold) and sodium butyrate (1.4 fold). These data strongly suggest that SCC production of SKG-IIIa cells is stimulated by peplomycin and sodium butyrate in vitro. In vivo experiments were also performed by administering peplomycin to nude rats with heterotransplanted tumors of SKG-IIIa, and transient elevations of serum SCC level (113% to 238% of the initial values) were observed, suggesting that SCC production of cancer cells is also stimulated by peplomycin in vivo.


Field phenotyping for African crops: overview and perspectives.
Improvements in crop productivity are required to meet the dietary demands of the rapidly-increasing African population. The development of key staple crop cultivars that are high-yielding and resilient to biotic and abiotic stresses is essential. To contribute to this objective, high-throughput plant phenotyping approaches are important enablers for the African plant science community to measure complex quantitative phenotypes and to establish the genetic basis of agriculturally relevant traits. These advances will facilitate the screening of germplasm for optimum performance and adaptation to low-input agriculture and resource-constrained environments. Increasing the capacity to investigate plant function and structure through non-invasive technologies is an effective strategy to aid plant breeding and additionally may contribute to precision agriculture. However, despite the significant global advances in basic knowledge and sensor technology for plant phenotyping, Africa still lags behind in the development and implementation of these systems due to several practical, financial, geographical and political barriers. Currently, field phenotyping is mostly carried out by manual methods that are prone to error, costly, labor-intensive and may come with adverse economic implications. Therefore, improvements in advanced field phenotyping capabilities and appropriate implementation are key factors for success in modern breeding and agricultural monitoring. In this review, we provide an overview of the current state of field phenotyping and the challenges limiting its implementation in some African countries. We suggest that the lack of appropriate field phenotyping infrastructures is impeding the development of improved crop cultivars and will have a detrimental impact on the agricultural sector and on food security. We highlight the prospects for integrating emerging and advanced low-cost phenotyping technologies into breeding protocols and characterizing crop responses to environmental challenges in field experimentation. Finally, we explore strategies for overcoming the barriers and maximizing the full potential of emerging field phenotyping technologies in African agriculture. This review paper will open new windows and provide new perspectives for breeders and the entire plant science community in Africa.


The demonstration of in vivo misonidazole tumour toxicity using post radiation hypoxia.
The cytotoxic effect of the radiosensitizer misonidazole on hypoxic tumour cells in vivo has been studied. Using standard procedures of large single doses of X-ray (30 Gy) followed by 1.0 mg/g misonidazole, no significant cytotoxicity (measured by tumour regrowth) could be observed. In contrast, when utilizing post radiation hypoxia (3 h of 7% oxygen breathing) in conjunction with post radiation misonidazole, an increased amount of direct drug toxicity was demonstrated. The use of this acute hypoxia treatment may prove to be a useful tool for measuring various in vivo radiobiological responses.


Macular Edema - Rationale for Therapy.
Macular edema represents the end-stage of multiple pathophysiological pathways in a multitude of ocular vascular, inflammatory, and other diseases. The rationale for clinical treatment of macular edema is based on the understanding and the inhibition of these pathophysiological mechanisms. When macular edema is caused by a generalized health problem such as diabetes, high blood pressure, or generalized inflammatory conditions, treatment of these generalized diseases can in many cases cure macular edema directly. In ocular diseases, the local exudation of fluid from blood vessels is governed by Starling's law as well as by intricate cellular mechanisms linked to the tight junctions in the inner and outer blood-retinal barrier. Drugs used in clinical practice, such as nonsteroidal anti-inflammatory drugs, corticosteroids, carbonic anhydrase inhibitors, and anti-vascular endothelial growth factor agents, all act in one way or another through these cellular mechanisms. Novel treatments such as neuroprotective agents like nerve growth factors, somatostatins and antiapoptotic agents like calpain, the glutamate blocker memantine, and different caspase inhibitors may in the future inhibit neuronal cell death in the retina by separate pathways. Using dimmed nocturnal illumination may be an additional novel method to reduce hypoxic stress during dark adaptation of the rod photoreceptors in diabetes. Successful surgical treatment of macular edema using vitrectomy and peeling relies, apart from the evident release of vitreomacular traction, on many other cellular and biochemical mechanisms activated by the surgery such as oxygenation of the inner retina, removal of the posterior hyaloid as a growth factor sink, and possible Müller cell remodeling with fluid redirection after internal limiting membrane peeling.


Minimal Invasive Treatment in Pelvic-Ureteric Junction Obstruction: A Comprehensive Review.
Pelvic-ureteric junction obstruction (PUJO) is a common condition, and one of the lead causes of hydronephrosis in children. Currently, the gold standard treatment of PUJO is open surgery using the Anderson-Hynes-modified dismembered pyeloplasty technique. However, with the advancement of medical technology, several minimal invasive approaches were developed, including endoscopic, laparoscopic, and robotic approach, from which the best choice of surgical technique was yet to be determined. Considering the advantages and disadvantages of these methods, the recommended option is to tailor the best surgical approach to each individual patient, and to the surgeons' preference and experience. Considering these recent advances, a new algorithm is proposed to choose the best minimal invasive modalities invasive treatment to treat PUJO.


Pattern of acute glomerulonephritis in adult population in Dubai: A single-center experience.
Epidemiological data of renal diseases have great geographic variability throughout the world. Due to the lack of a national renal data registry system, there is no information on the prevalence rate, clinical and pathological features of various glomerulonephritis (GN) in the United Arab Emirates (UAE). In a retrospective cross-sectional study, we analyzed 158 renal biopsies done in Dubai Hospital, UAE, between the years of 2005 and September 2014, with an aim to determine the prevalence rate and frequency of different pathological patterns of GN in adult patients who presented with proteinuria ± hematuria. In our study, primary GN still remains more common than secondary GN (66.4% vs. 33.5%). Among the primary GN in our analysis, minimal change disease was the most common primary GN affecting 20% of the study population (13.2% of the total GN causes) followed with membranous GN (18.2%), then membrano- proliferative GN (15.3%) and focal segmental glomerulosclerosis (13.46%), while among the secondary causes lupus nephritis (LN) is the most prevalent GN in UAE, predominantly in the Emirati national population whom constituted 48% of total biopsies. Indeed, LN had the highest incidence among all types of GN even the primary ones, constituting 23.4% of total GN in Dubai (74% of the total secondary causes). Furthermore, systemic lupus erythematosus was the most common GN in women while the minimal change was widely affecting male patients. Among elderly, the most common pathology was diabetic glomerulosclerosis followed by amyloidosis.


Clinical efficacy with dabrafenib and trametinib in a T599_V600insT poorly differentiated metastatic thyroid carcinoma.
BRAF (v-raf murine sarcoma viral oncogene homolog B1) and MEK (mitogen-activated protein kinase kinase) inhibitors have been shown to improve clinical outcomes in tumours presenting with mutations in the BRAF gene. The most common form of BRAF mutation is V600E/K and has been shown to occur in thyroid cancers. Treatment data for patients harbouring less frequent BRAF mutations are limited. In vitro studies have shown that mutations in codons 599-601 increase kinase activity similar to that in V600E mutations, which suggests that BRAF and MEK inhibitors could be an effective treatment option. Here, we report a case of a patient with thyroid carcinoma harbouring a rare amino acid insertion in codon 599 of the BRAF gene (T599_V600insT) treated with a BRAF and MEK inhibitor.


A mechanism of formation of a persistent hybrid between elongating RNA and template DNA.
At the replication origin of ColE1 plasmid, a persistent hybrid is formed between the primer precursor (RNA II) and its template DNA. The wild-type sequence in the region 13 to 20 bp upstream (-20 region) of the origin is required to form this persistent hybrid. While the template strand for transcription of this region, containing a stretch of six dC residues, is needed, the nontemplate strand can be deleted. Certain mutations in far upstream regions that prevent hybrid formation are suppressed by the nontemplate strand deletion. In RNA II that is forming a persistent hybrid, the region about 265 nucleotides upstream of the origin (-265 region) can also form a hybrid with the template DNA. The -265 region of RNA II that consists of a stretch of six rG residues probably interacts with the dC stretch of the -20 region in the template strand to promote hybrid formation.


Generalized motor abilities and timing behavior in children with specific language impairment.
To examine whether children with specific language impairment (SLI) differ from normally developing peers in motor skills, especially those skills related to timing. Standard measures of gross and fine motor development were obtained. Furthermore, finger and hand movements were recorded while children engaged in 4 different timing tasks, including tapping and drawing circles in time with a metronome or a visual target. Fourteen children with SLI (age 6 to 8 years) and 14 age-matched peers who were typically developing participated. As expected, children with SLI showed poorer performance on a standardized test of gross and fine motor skill than did their normally developing peers. However, timing skill in the manual domain was equivalent to that seen in typically developing children. Consistent with earlier findings, relatively poor gross and fine motor performance is observed in children with SLI. Surprisingly, rhythmic timing is spared.


Securing Cooperative Spectrum Sensing Against Collusive SSDF Attack using XOR Distance Analysis in Cognitive Radio Networks.
Cooperative spectrum sensing (CSS) is considered as a powerful approach to improve the utilization of scarce spectrum resources. However, if CSS assumes that all secondary users (SU) are honest, it may offer opportunities for attackers to conduct a spectrum sensing data falsification (SSDF) attack. To suppress such a threat, recent efforts have been made to develop trust mechanisms. Currently, some attackers can collude with each other to form a collusive clique, and thus not only increase the power of SSDF attack but also avoid the detection of a trust mechanism. Noting the duality of sensing data, we propose a defense scheme called XDA from the perspective of XOR distance analysis to suppress a collusive SSDF attack. In the XDA scheme, the XOR distance calculation in line with the type of "0" and "1" historical sensing data is used to measure the similarity between any two SUs. Noting that collusive SSDF attackers hold high trust value and the minimum XOR distance, the algorithm to detect collusive SSDF attackers is designed. Meanwhile, the XDA scheme can perfect the trust mechanism to correct collusive SSDF attackers' trust value. Simulation results show that the XDA scheme can enhance the accuracy of trust evaluation, and thus successfully reduce the power of collusive SSDF attack against CSS.


Fetal gender impact on multiple-marker screening results.
Maternal serum alpha-fetoprotein (MSAFP), human chorionic gonadotropin (hCG), and unconjugated estriol (uE3) are used in combination with maternal age to calculate the risk for Down syndrome (DS) in pregnancy. Increased levels of hCG and decreased levels of MSAFP and uE3 are consistent with an increased risk for DS. We retrospectively evaluated second-trimester maternal serum marker levels in a large cohort of patients with known normal outcomes and documented fetal gender. These included 15,428 patients who had MSAFP measurements, 11,428 patients with both MSAFP and hCG, and 6,090 patients with all three markers including uE3. MSAFP levels in patients with female fetuses were consistently lower than those with males. Conversely, hCG was higher in pregnancies with females as compared to males. No gender-related difference was noted for uE3. These results would suggest that the computed DS risk for female fetuses is higher than for males, despite the fact that the incidence of DS is similar in both genders. This information could be useful for calculating gender-specific DS risk; however, this would require ultrasonographic determination of fetal sex.


Contributions of Child Sexual Abuse, Self-Blame, Posttraumatic Stress Symptoms, and Alcohol Use to Women's Risk for Forcible and Substance-Facilitated Sexual Assault.
Child sexual abuse and adult sexual assault have been linked to increased self-blame, posttraumatic stress symptoms, and alcohol use. The current study aims to examine (a) whether these constructs explain women's risk for later adult sexual assault and revictimization, (b) whether such factors differentially confer risk for specific types of adult sexual assault (i.e., substance-facilitated and forcible), and (c) if self-blame confers risk indirectly through other risk factors. Multiple types of self-blame, posttraumatic stress, and alcohol use were examined among 929 female college students as serial mediators of the relationship between child sexual abuse and adult sexual assault and as risk factors for sexual revictimization among child sexual abuse survivors. In the model predicting risk for substance-facilitated adult sexual assault, child sexual abuse indirectly predicted greater risk for substance-facilitated adult sexual assault mediated through two separate paths: global blame-to-posttraumatic-stress and global blame-to-alcohol use. In the model predicting risk for forcible adult sexual assault, child sexual abuse directly predicted greater risk for forcible adult sexual assault, and this relation was mediated by the global blame-to-posttraumatic-stress path. Among child sexual abuse survivors, child sexual abuse specific characterological and behavioral self-blame directly predicted greater risk for forcible and substance-facilitated revictimization, but the pathways were not mediated by posttraumatic stress or alcohol use. Results emphasize the importance of assessing different types of self-blame in predicting posttraumatic stress symptoms as well as examining risk for sexual victimization and revictimization. Findings did not support hypotheses that increased posttraumatic stress would predict increased alcohol use but did indicate that heightened self-blame is consistently associated with heightened posttraumatic stress and that heightened global self-blame predicts increased alcohol use. Implications for future research and intervention are discussed.


Immunoliposome co-delivery of bufalin and anti-CD40 antibody adjuvant induces synergetic therapeutic efficacy against melanoma.
Liposomes constitute one of the most popular nanocarriers for improving the delivery and efficacy of agents in cancer patients. The purpose of this study was to design and evaluate immunoliposome co-delivery of bufalin and anti-CD40 to induce synergetic therapeutic efficacy while eliminating systemic side effects. Bufalin liposomes (BFL) conjugated with anti-CD40 antibody (anti-CD40-BFL) showed enhanced cytotoxicity compared with bufalin alone. In a mouse B16 melanoma model, intravenous injection of anti-CD40-BFL achieved smaller tumor volume than did treatment with BFL (average: 117 mm(3) versus 270 mm(3), respectively); the enhanced therapeutic efficacy through a caspase-dependent pathway induced apoptosis, which was confirmed using terminal deoxynucleotidyl transferase-mediated dUTP-Fluorescein nick end labeling and Western blot assay. Meanwhile, anti-CD40-BFL elicited unapparent body-weight changes and a significant reduction in serum levels of tumor necrosis factor-α, interleukin-1β, interleukin-6, interferon-γ, and hepatic enzyme alanine transaminase, suggesting minimized systemic side effects. This may be attributed to the mechanism by which liposomes are retained within the tumor site for an extended period of time, which is supported by the following biodistribution and flow cytometric analyses. Taken together, the results demonstrated a highly promising strategy for liposomal vehicle transport of anti-CD40 plus bufalin that can be used to enhance antitumor effects via synergetic systemic immunity while blocking systemic toxicity.


Physician Perception of the Role of the Patient Portal in Pediatric Health.
The patient portal, increasingly available to patients, allows secure electronic communication with physicians. Although physician attitude toward the portal plays a crucial role in patient adoption, little information regarding physician opinion of the portal is available, with almost no information gathered in the pediatric environment. Using a mixed-methods approach, physicians in a large pediatric medical facility and integrated delivery network were surveyed using an online quantitative questionnaire and structured interviews. Physicians reported the portal's role in more communication efficiency for patients, parents, and providers. The portal's acceptance also introduces new challenges such as frequent questions from some parents and medical visit avoidance.


The effect of leptin replacement on sleep-disordered breathing in the leptin-deficient ob/ob mouse.
Obese leptin-deficient (ob/ob) mice demonstrate defects in upper airway structural and neuromuscular control. We hypothesized that these defects predispose to upper airway obstruction during sleep, and improve with leptin administration. High-fidelity polysomnographic recordings were conducted to characterize sleep and breathing patterns in conscious, unrestrained ob/ob mice (23 wk, 67.2 ± 4.1 g, n = 13). In a parallel-arm crossover study, we compared responses to subcutaneous leptin (1 μg/h) vs. vehicle on respiratory parameters during NREM and REM sleep. Upper airway obstruction was defined by the presence of inspiratory airflow limitation (IFL), as characterized by an early inspiratory plateau in airflow at a maximum level (V̇Imax) with increasing effort. The severity of upper airway obstruction (V̇Imax) was assessed along with minute ventilation (V̇E), tidal volume (VT), respiratory rate (RR), inspiratory duty cycle, and mean inspiratory flow at each time point. IFL occurred more frequently in REM sleep (37.6 ± 0.2% vs. 1.1 ± 0.0% in NREM sleep, P < 0.001), and leptin did not alter its frequency. V̇Imax (3.7 ± 1.1 vs. 2.7 ± 0.8 ml/s, P < 0.001) and V̇E increased (55.4 ± 22.0 vs. 39.8 ± 16.4 ml/min, P < 0.001) with leptin vs. vehicle administration. The increase in V̇E was due to a significant increase in VT (0.20 ± 0.06 vs. 0.16 ± 0.05 ml, P < 0.01) rather than RR. Increases in V̇E were attributable to increases in mean inspiratory flow (2.5 ± 0.8 vs. 1.8 ± 0.6 ml/s, P < 0.001) rather than inspiratory duty cycle. Similar increases in V̇E and its components were observed in non-flow-limited breaths during NREM and REM sleep. These responses suggest that leptin stabilized pharyngeal patency and increased drive to both the upper airway and diaphragm during sleep.


High olfactory sensitivity to conspecific intestinal fluid in the chameleon cichlid Australoheros facetus: could faeces signal dominance?
The present study shows that the olfactory potency of intestinal and bile fluids taken from dominant male chameleon cichlids Australoheros facetus is greater than those from subordinate males. Thus, dominant status may be communicated by odorants released in the intestinal fluid and bile acids may contribute towards this.


Pulmonary infiltrates associated with noncytotoxic drugs.
A wide variety of noncytotoxic drugs, including antibiotics, analgesics, narcotics, and psychotrophic and cardiovascular agents, may cause lung injury accompanied by roentgenographic infiltrates. The clinical manifestations of drug-induced lung disease are protean. Patients may present with acute injury resembling the adult respiratory distress syndrome, which must initially be distinguished from bacterial sepsis. Other drug-associated lung injury is characterized by a more subacute pneumonitis similar to an atypical infectious pneumonia. Finally, some drugs may cause insidiously progressive pulmonary infiltrates that share features with granulomatous infections. The more common drug reactions are discussed in this review, and, although the features of drug-induced lung disease are often relatively nonspecific, those features that either mimic infectious causes or may be helpful in differentiating these processes from infections are given particular emphasis.


Amyloid Aggregation of Streptococcus mutans Cnm Influences Its Collagen-Binding Activity.
The cnm gene, coding for the glycosylated collagen- and laminin-binding surface adhesin Cnm, is found in the genomes of approximately 20% of Streptococcus mutans clinical isolates and is associated with systemic infections and increased caries risk. Other surface-associated collagen-binding proteins of S. mutans, such as P1 and WapA, have been demonstrated to form an amyloid quaternary structure with functional implications within biofilms. In silico analysis predicted that the β-sheet-rich N-terminal collagen-binding domain (CBD) of Cnm has a propensity for amyloid aggregation, whereas the threonine-rich C-terminal domain was predicted to be disorganized. In this study, thioflavin-T fluorescence and electron microscopy were used to show that Cnm forms amyloids in either its native glycosylated or recombinant nonglycosylated form and that the CBD of Cnm is the main amyloidogenic unit of Cnm. We then performed a series of in vitro, ex vivo, and in vivo assays to characterize the amylogenic properties of Cnm. In addition, Congo red birefringence indicated that Cnm is a major amyloidogenic protein of S. mutans biofilms. Competitive binding assays using collagen-coated microtiter plates and dental roots, a substrate rich in collagen, revealed that Cnm monomers inhibit S. mutans binding to collagenous substrates, whereas Cnm amyloid aggregates lose this property. Thus, while Cnm contributes to recognition and initial binding of S. mutans to collagen-rich surfaces, amyloid formation by Cnm might act as a negative regulatory mechanism to modulate collagen-binding activity within S. mutans biofilms and warrants further investigation. IMPORTANCE Streptococcus mutans is a keystone pathogen that promotes caries by acidifying the dental biofilm milieu. The collagen- and laminin-binding glycoprotein Cnm is a virulence factor of S. mutans. Expression of Cnm by S. mutans is hypothesized to contribute to niche expansion, allowing colonization of multiple sites in the body, including collagen-rich surfaces such as dentin and heart valves. Here, we suggest that Cnm function might be modulated by its aggregation status. As a monomer, its primary function is to promote attachment to collagenous substrates via its collagen-binding domain (CBD). However, in later stages of biofilm maturation, the same CBD of Cnm could self-assemble into amyloid fibrils, losing the ability to bind to collagen and likely becoming a component of the biofilm matrix. Our findings shed light on the role of functional amyloids in S. mutans pathobiology and ecology.


Multiple site-directed mutagenesis via simple cloning by prolonged overlap extension.
We describe the application of simple cloning by prolonged overlap extension for multiple site-directed mutagenesis in the same plasmid. We show that it is possible to use this technique with very short PCR templates. The technique is ideally suited for the generation of longer donor DNA sequences for CRISPR/Cas9-mediated homologous repair.


Bayesian Machine Learning Techniques for revealing complex interactions among genetic and clinical factors in association with extra-intestinal Manifestations in IBD patients.
The objective of the study is to assess the predictive performance of three different techniques as classifiers for extra-intestinal manifestations in 152 patients with Crohn's disease. Naïve Bayes, Bayesian Additive Regression Trees and Bayesian Networks implemented using a Greedy Thick Thinning algorithm for learning dependencies among variables and EM algorithm for learning conditional probabilities associated to each variable are taken into account. Three sets of variables were considered: (i) disease characteristics: presentation, behavior and location (ii) risk factors: age, gender, smoke and familiarity and (iii) genetic polymorphisms of the NOD2, CD14, TNFA, IL12B, and IL1RN genes, whose involvement in Crohn's disease is known or suspected. Extra-intestinal manifestations occurred in 75 patients. Bayesian Networks achieved accuracy of 82% when considering only clinical factors and 89% when considering also genetic information, outperforming the other techniques. CD14 has a small predicting capability. Adding TNFA, IL12B to the 3020insC NOD2 variant improved the accuracy.


[Mitral annulus calcification: clinical observation on 72 patients].
This report presents 72 cases with mitral annulus calcification. The diagnosis was made by echocardiogram. There were 21 males and 51 females, aged from 38 to 93 (mean 71). The associated clinical findings in these 72 patients included: hypertension, 28 cases; valvular aortic stenosis, 3 cases; hypertrophic cardiomyopathy, 7 cases; chronic renal failure, 14 cases; congestive heart failure, 29 cases, calcified aortic valve, 27 cases; mitral regurgitation, 46 cases; cerebral infarct, 19 cases; peripheral arterial embolism, 2 cases. Their electrocardiographic findings included: atrial fibrillation, 25 cases; conduction defects, 21 cases; sick sinus syndrome, 3 cases (one case required permanent pacemaker implantation). We conclude that mitral annulus calcification is not a senile change only, and that it also results in some complications such as: mitral regurgitation, cerebral embolism, peripheral arterial embolism, atrial fibrillation and conduction defects. Echocardiography is a useful diagnostic tool in the evaluation of patients with mitral annulus calcification.


Prevalence of depression and its association with sociodemographic factors in patients with chronic pain: A cross-sectional study in a tertiary care hospital in Saudi Arabia.
Mental health issues, especially depression, are common in chronic pain patients. Depression affects these patients negatively and could lead to poor control of their pain. Some risk factors for both chronic pain and depression are known and need to be targeted as part of the management in a multidisciplinary approach. This study was conducted to estimate the prevalence of depression among chronic pain patients attending a pain clinic and to explore the association between depression in chronic pain patients and other factors such as sociodemographic features, number of pain sites, severity of pain, and types of pain. This is a cross-sectional study that carried out in a chronic pain clinic in a tertiary care hospital in Riyadh, Saudi Arabia (King Faisal Specialist Hospital and Research Centre). All chronic pain patients including cancer-related pain, apart from acute pain patients and children, were eligible to participate in the study. Association between depression and sociodemographic factors was assessed with univariate and multivariate methods. Main outcome measures were the prevalence of depression in chronic pain patients using the Patient Health Questionnaire-9 (PHQ-9) and the association with sociodemographic factors. A total of 200 chronic pain patients (128 females [64%]) participated in the study. The prevalence of depression was 71% (95% confidence interval: 64.7-77.3) based on the PHQ-9 diagnostic criteria using a cutoff point of >5. Among those patients who were depressed, 9 (4.5%) had severe depression as compared to 31 (15.5%), 41 (20.5%), and 61 (30.5%) who had moderately severe, moderate, and mild depression, respectively. Depression (scored at the cutoff point of 5) in chronic pain patients was significantly associated with age, financial status, medical history of depression, and pain severity. Depression is common among chronic pain patients with several risk factors aggravating its presentation. Due to their increased risk of depression, psychiatric counseling that offers mental health assistance should be prioritized and made available as a multidisciplinary approach for the treatment of chronic pain patients.


An original Eurasian haplotype, HLA-DRB1*14:54-DQB1*05:03, influences the susceptibility to idiopathic achalasia.
Idiopathic achalasia is a relatively infrequent esophageal motor disorder for which major histocompatibility complex (MHC) genes are well-identified risk factors. However, no information about HLA-achalasia susceptibility in Mexicans has previously been reported. We studied a group of 91 patients diagnosed with achalasia and 234 healthy controls with Mexican admixed ancestry. HLA alleles and conserved extended haplotypes were analyzed using high-resolution HLA typing based on Sanger and next-generation sequencing technologies. Admixture estimates were determined using HLA-B and short tandem repeats. Results were analyzed by non-parametric statistical analysis and Bonferroni correction. P-values < 0.05 were considered significant. Patients with achalasia had 56.7% Native American genes, 24.7% European genes, 16.5% African genes and 2.0% Asian genes, which was comparable with the estimates in the controls. Significant increases in the frequencies of alleles DRB1*14:54 and DQB1*05:03 and the extended haplotypes DRB1*14:54-DQB1*05:03 and DRB1*11:01-DQB1*03:01, even after Bonferroni correction (pC<0.05), were found in the achalasia group compared to those in the controls. Concluding, the HLA class II alleles HLA-DRB1*14:54:01 and DQB1*05:03:01 and the extended haplotype are risk factors for achalasia in mixed-ancestry Mexican individuals. These results also suggest that the HLA-DRB1*14:54-DQB1*05:03 haplotype was introduced by admixture with European and/or Asian populations.


Influence of yoga on blood coagulation.
Yoga is known to induce beneficial effects on physiological, biochemical and mental functions in man. Its effects on blood coagulation are not known. A study was conducted in seven previously untrained male adults who underwent a combination of yogic exercises, daily for one hour, over a period of four months. Parameters of blood coagulation were estimated before and after the end of yoga training. The following changes were observed: Fibrinolytic activity increased significantly with a concomitant fall in fibrinogen; activated partial thromboplastin time and platelet aggregation time were prolonged; blood and plasma platelets showed a rise; and both haemoglobin and heamatocrit were raised at the end of the training. These findings suggest that yoga induces a state of blood hypocoagulability. The impact of yoga on prevention of cardiovascular and thrombotic disorders is obvious.


Thermal characteristics of a common polystyrene phantom.
We have examined the thermal characteristics of a polystyrene phantom of the SCRAD type. In the case of a calibration phantom which is moved from one location to another, many hours may be required to achieve thermal equilibrium with the new environment. By using a correction term based on the temperature of the phantom, not of the room, it is possible to calibrate a therapy unit without waiting for thermal equilibrium.


Interaction of formaldehyde with a water-tolerant frustrated Lewis pair.
A facile complexation of formaldehyde with the water-tolerant frustrated Lewis pair (FLP) B(C6F5)3/PtBu3 and its Al-analog under ambient conditions is reported. Unprecedented formaldehyde adducts 1, 2 and 4 have been identified and crystallographically characterized.


Nine phthalate metabolites in human urine for the comparison of health risk between population groups with different water consumptions.
Phthalates are a group of high production volume chemicals widely detected in environment matrix and human specimens. Potential health risks due to the prevalence of their exposure through water consumption and the endocrine-disrupting activities have become an important issue. This work aims to compare the distributions of phthalate levels and potential health risks caused by phthalate exposure among three groups of participants ingesting different types of water. Here, a method with good performance was applied for the analysis of nine common phthalate metabolites in 125 human urine samples collected from Wuhan women. Seven analytes (mono‑ethyl, mono‑benzyl, mono‑n‑butyl, mono‑(2‑ethylhexyl), mono‑(2‑ethyl‑5‑oxohexyl), mono‑(2‑ethyl‑5‑hydroxyhexyl), and mono‑(2‑ethyl‑5‑carboxypentyl) phthalate) were detected in over 80% of the samples. By measuring urinary concentrations of phthalate monoesters, the exposure levels of respective parent phthalates, exposure patterns, the estimated daily intakes and accumulative risk assessments were investigated in three groups of participants consuming water from different sources (bottled water, filtered water and boiled tap water). The results showed that the exposure patterns of phthalates varied among the population groups with different water intakes, and the health risk was higher for people ingesting the boiled tap water than that of the groups consuming bottled water (purified water) and filtered water with filter cartridge containing activated carbon.


Cytotoxicity of Natural Killer Cells Activated Through NKG2D Contributes to the Development of Bronchiolitis Obliterans in a Murine Heterotopic Tracheal Transplant Model.
Bronchiolitis obliterans after lung transplantation is a major cause of postoperative mortality in which T cell-mediated immunity is known to play an important role. However, the exact contribution of natural killer (NK) cells, which have functions similar to CD8+ T cells, has not been defined. Here, we assessed the role of NK cells in murine bronchiolitis obliterans through heterotopic tracheal transplantations and found a greater percentage of NK cells in allografts than in isografts. Depletion of NK cells using an anti-NK1.1 antibody attenuated bronchiolitis obliterans in transplant recipients compared with controls. In terms of NK cell effector functions, an improvement in bronchiolitis obliterans was observed in perforin-KO recipient mice compared to wild type (WT). Furthermore, we found upregulation of NKG2D-ligand in allografts and demonstrated the significance of this using grafts expressing Rae-1, a murine NKG2D-ligand, which induced severe bronchiolitis obliterans in WT and Rag-1 KO recipients. This effect was ameliorated by injection of anti-NKG2D blocking antibody. Together, these results suggest that cytotoxicity resulting from activation of NK cells through NKG2D leads to the development of murine bronchiolitis obliterans.


Penicillin susceptibility among invasive MSSA infections: a multicentre study in 16 Spanish hospitals.
To determine the prevalence of penicillin susceptibility among MSSA causing bloodstream infections (BSIs) in 16 Spanish hospitals and to characterize the penicillin-susceptible MSSA (MSSA-PENS) isolates. A total of 1011 Staphylococcus aureus isolates were collected from blood cultures in 16 Spanish hospitals during 2018-19 (6-12 months) and their susceptibility to 18 antimicrobials was determined. The MSSA-PENS isolates were selected and examined by PCR to determine the presence of the blaZ gene, other resistance genes and the genes lukF/lukS-PV, eta, etb and tst. The immune evasion cluster (IEC) type was also analysed. All the MSSA-PENS isolates were submitted to S. aureus protein A (spa) typing and the clonal complexes (CCs) were assigned according to their spa type. The prevalence of MSSA was 74.6% (754/1011) and 14.9% (151/1011) were MSSA-PENS-blaZnegative. MSSA-PENS-blaZnegative isolates (n = 151) were ascribed to 88 spa types and 11 CCs. The most frequent CCs were CC5 (35/151) and CC398 (25/151), with t002-CC5 and t571-CC398 being the most common lineages. Pan-susceptibility was identified in 117 of the 151 MSSA-PENS-blaZnegative isolates (77.5%). In the remaining isolates, erythromycin and clindamycin resistance was the most frequent resistance found, although tobramycin, ciprofloxacin, fusidic acid, mupirocin and/or tetracycline resistance was also detected. Thirty-eight MSSA-PENS-blaZnegative isolates were IEC negative and four isolates were Panton-Valentine leucocidin ('PVL') positive. A high penicillin susceptibility rate was detected among MSSA, opening therapeutic opportunities for BSIs. The emergence of new successful MSSA-PENS clones could be responsible for these data. The detection among MSSA-PENS-blaZnegative isolates of the clonal lineage CC398 or the absence of an IEC raises questions about their possible animal origin, requiring further analysis.


Inverse design of sub-wavelength convergent grating based on the "stepped particle swarm algorithm".
In this Letter, a novel "stepped particle swarm optimization" (SPSO) based on field intensity adjustment is proposed. After that, we used this algorithm to design a sub-wavelength converging grating that could be integrated with the detector on the back. Firstly, the advantages of reverse design in the process of two-dimensional or multi-element grating pattern design were summarized by comparing the theory of forward and reverse design. Then, the common "particle swarm optimization" (PSO) and our proposal were compared in the reverse design process; we found that the field strength at the focal point obtained by the improved algorithm was approximately twice of the conventional PSO, and the SPSO had higher computational efficiency and better global convergence. The value of the SPSO had been steadily enlarged, which significantly improved the performance of the sub-wavelength convergent grating. Finally, the property of the sub-wavelength converging grating was simulated, and we found that the grating could achieve good convergence in the focal length range of 100-150 µm, and had a strong ability to compensate for the position deviation of the incident light. In actual optical communications, this sub-wavelength converging grating will play an important role in alleviating the bandwidth and quantum efficiency, improving the performance of the detectors.


Total Synthesis of ent-Pregnanolone Sulfate and Its Biological Investigation at the NMDA Receptor.
A unique asymmetric total synthesis of the unnatural enantiomer of pregnanolone, as well as a study of its biological activity at the NMDA receptor, is reported. The asymmetry is introduced by a highly atom-economic organocatalytic Robinson annulation. A new method for the construction of the cyclopentane D-ring consisting of CuI-catalyzed conjugate addition and oxygenation followed by thermal cyclization employing the persistent radical effect was developed. ent-Pregnanolone sulfate is surprisingly only 2.6-fold less active than the natural neurosteroid.


The endogenous--neurotic distinction as a predictor of response to antidepressant drugs.
An inverse factor analysis of 880 depressed inpatients on 33 endogenous-neurotic variables yielded four patient types. Type 3 resembled the endogenous depressions and Type 2 the neurotic depressions. Type 3 patients responded well to both imipramine and chlorpromazine and did poorly on a placebo. Type 2 patients showed the greatest overall improvement at three weeks irrespective of treatment received, including a placebo.


The results of functional (Sarmiento) bracing of humeral shaft fractures.
At the Department of Orthopaedics of the Kantonsspital Fribourg, 67 humeral shaft fractures were treated by Sarmiento bracing in a 15-year period. There were 54 isolated fractures and 13 fractures sustained as a component of polytrauma. Fifty-eight cases (87%) had healed clinically at a mean of 10 weeks; 9 cases failed to heal, so further treatment was carried out operatively. Of the conservatively managed fractures, 95% (55 cases) healed with an excellent or good result. Three patients noted a slight limitation of active range of motion, but all 58 patients returned to full duty at their jobs. Among 9 patients with delayed or nonunion leading to operative intervention, there were 6 cases with transverse fractures. Major reasons for failed conservative management were an incorrect indication, a significant axial deformity, or a hyperextended position of the fracture fragments. In our experience, active repositioning of humeral shaft fractures is not effective in avoiding a delay in fracture healing. The decision to use functional bracing in polytrauma patients should depend on the time of expected bedridden immobilization, on the presence of additional fractures of the ipsilateral upper extremity, and on the patient's need for crutches. The conservative treatment of humeral shaft fractures with the Sarmiento brace remains the treatment of choice, in spite of newer intramedullary operations that are allegedly minimally invasive and technically less complicated.


Back and hip extensor fatigability in chronic low back pain patients and controls.
To compare the lumbar paraspinal and gluteus maximus muscle fatigability between chronic low back pain patients and healthy controls by using electromyographic (EMG) spectral analysis during a maximal isometric endurance task. A cross-sectional comparative study between chronic low back pain patients and healthy control subjects. Physical medicine and rehabilitation clinic in Finland. Twenty women with nonspecific chronic low back pain (longer than 3 months) and 15 healthy controls. Subjects performed maximal voluntary isometric back extensions (MVC) at 30 degrees forward flexion in a specially designed measurement unit. A 50% MVC load was used in isometric endurance test. Low back pain intensity was assessed by using the visual analogue scale and functional disability by the Oswestry disability index. Time to endurance was measured. Bipolar surface EMG recordings were made over the lumbar paraspinal muscles (L3-L4, L5-S1) and over the gluteus maximus muscles. Average EMG (aEMG%), and initial spectral median frequency (MFinit) and change over time (MFslope) were computed. Pain intensity and functional disability were higher and MVC and time to endurance were lower in the chronic low back pain group (p < .05). Similar muscle activity levels (aEMG%) and MFinit indicated similar muscle loading in both groups at the beginning of the endurance test. EMG spectral decreases (MFslope) indicated that lumbar paraspinal muscle fatigability was similar in both groups. In the chronic low back pain group, the gluteus maximus fatigued faster than in the control group (greater MFslope, p < .05). However, the shorter endurance time indicated greater fatigability in the chronic low back pain group in general (p < .05). The chronic low back pain patients were weaker and fatigued faster than the healthy controls. The EMG fatigue analysis results suggest that the gluteus maximus muscles are more fatigable in chronic low back pain patients than in healthy control subjects during a sustained back extension endurance test.


Factors Affecting Patient Adherence to Multivitamin Intake After Bariatric Surgery: Thematic Analysis of Qualitative Data From a Multicenter Study.
Introduction Adherence to daily intake of multivitamin supplementation (MVS) is a major challenge after bariatric surgery (BS). The aim of this study was to identify insights into patients' beliefs and experiences on adherence to MVS intake. Methods A thematic analysis of qualitative data from four high-volume bariatric centers in the Netherlands was conducted. A series of texts from the open-ended question of 1,246 patients were thematically analyzed for common or overarching themes, ideas, and patterns. Results Five key themes emerged regarding participants' suggestions on adherence to daily MVS intake: "gastrointestinal side effects to MVS intake" (n = 850, 68.2%), "negative features of MVS" (n = 296, 23.8%), "satisfaction with advice on MVS" (n = 272, 21.8%), "dissatisfaction with service provision" (n = 160, 12.8%), and "costs" (n = 93, 7.5%). Most problems were experienced when using specialized weight loss surgery (WLS) MVS. These supplements may cause gastrointestinal side effects, and costs are too high. After bariatric surgery, numerous patients strongly felt that information provision was poor in several aspects, and the aftercare pathway process did not provide sufficient support. Conclusion This study found five major themes involved in patient adherence to multivitamin intake after BS: gastrointestinal side effects to MVS intake, negative features of MVS, satisfaction with advice on MVS, dissatisfaction with service provision, and costs of specialized MVS. Challenges lie in stronger education for both patients and healthcare professionals. More personalized care could probably increase patient satisfaction, and MVS companies should look at further optimizing supplements for better tolerability and reducing costs.


Shear bond strength of microwaveable acrylic resin for denture repair.
Microwaveable acrylic denture resins are believed to provide an effective means of repairing fractured dentures. This in vitro investigation compared the bond strength of a microwaveable acrylic resin as a denture repair material to two established auto-polymerized resins. Fifty-one specimens were made using Lucitone 199 as a simulated denture base, and were then divided into three groups of 17 samples each. Each test group was bonded with the following acrylic resins: Acron Mc, Rapid Repair and Palapress. A shear bond strength test was carried out 24 h after the samples were bonded. Fracture analysis showed that bond failure was adhesive for all groups. Shear bond values showed a statistically significant difference at P < 0.05 level between Acron Mc and Rapid Repair; Palapress and Rapid Repair, and indicated that Acron Mc and Palapress were superior to Rapid Repair as a repair material. However, there was no statistical difference found between Acron Mc and Palapress. Microwaveable acrylic resins produce repaired junctions of adequate strength.


Functional marker development is challenged by the ubiquity of endophytes-a practical perspective.
Functional markers (FMs) are supposed to assist in diagnosis, disease treatment and turning plant and animal breeding more efficient. However, efficient FM application is challenged through current insights in the multi-organism nature of life. This letter aims to raise awareness for re-thinking concepts for FM development in plant breeding and proposes a novel perspective.


Factor XIII-deficiency in the blood of venous leg ulcer patients.
Pericapillary fibrin cuffs are probably involved in the pathogenesis of venous leg ulcers. Factor XIII (Fibrin stabilizing factor) is of importance in wound healing. Its activity, which may affect ulceration, was found to be significantly reduced in the blood of venous leg ulcer patients and in post-phlebitic patients, compared with healthy controls.


Immunology and genetics of tumour necrosis factor in allergic contact dermatitis.
During the sensitization phase of allergic contact dermatitis, the proinflammatory cytokine tumour necrosis factor (TNF) plays an important role by promoting epidermal Langerhans cell migration to draining lymph nodes. It also plays a role during the elicitation phase. The TNF gene (TNF) is located within the major histocompatibility complex region. Many single-nucleotide variants exist in the promoter region of TNF, and these may either increase or decrease mRNA transcription and therefore lead to higher or lower levels of TNF. The most extensively studied single-nucleotide variant of TNF is a base pair substitution in the promoter region at location -308 relative to the transcription start site (rs1800629, TNF -308G>A), which is believed to increase transcription and lead to higher TNF levels. The role of TNF in allergic contact dermatitis and the functionality of TNF -308G>A are reviewed in this article. The association between genetic variants and disease can be studied in a case-control design. Only a few case-control studies investigating the association between TNF -308G>A and allergic contact dermatitis have been published, with contradictory results. These are reviewed critically, and suggestions for future case-control studies on this topic are made.


[A totally implantable permanent central venous access, long-term experience with subcutaneous infusion chambers].
Subcutaneously implanted infusion chambers represent a new method of central venous access. In 57 evaluable out of 70 patients, four different models of infusion chambers with an accumulative observation time of 57 years were implanted. In 72% of the patients, up to 12 cycles of polychemotherapy were administered. Parenteral nutrition and blood drawing were also performed. After 4,970 punctions of the system and 12.2 years of use 46 complications in 38 patients were observed, however, most were minor ones, such as temporary occlusions (12) and extravasations (14). Septum luxation (1), septum perforation (1), catheter fracture (1) and catheter migration (2) as well as 7 cases of septicemia or port-pocket-infection required explanation. Infusion chambers seem to be particularly suitable for intermittent and long-term chemotherapy and emergency bolus injections with a significant advantage (10 complications per one thousand days of use) compared to externally placed venous catheters. However, follow-up and care must be performed by a skilled team.


Sagittal spino-pelvic alignment in adults: The Wakayama Spine Study.
To establish the normal values of spino-pelvic alignment and to clarify the effect of age-related changes using large, community-based cohorts. In this study, data from 1461 participants (466 men, 995 women) were analyzed. On lateral standing radiographs, the following parameters were measured: thoracic kyphosis (TK), lumbar lordosis (LL), pelvic tilt (PT), pelvic incidence (PI), and C7 sagittal vertical axis (SVA). All values are expressed as the mean±standard deviation. The Spearman rank correlation coefficient was used to examine correlations between variables of spino-pelvic parameters. Finally, we analyzed the relationship between age and spino-pelvic parameters. Therefore, we entered values for the body mass index (BMI), SVA, TK, and PI-LL into a multiple regression model to adjust for potential confounding factors. The SVA, TK, and PT increased with age, and LL decreased with age. Regarding sex differences, the TK was statistically significantly larger in men than in women, and LL, PT, and PI were statistically significantly smaller in men than in women. Correlation coefficients between the SVA and TK, between the SVA and PI-LL, and between TK and PI-LL were none, strong, and weak, respectively. Results of multiple regression analysis between age and spino-pelvic parameters showed that the standardized partial regression coefficients for the SVA, TK, and PI-LL were 0.17, 0.30, and 0.23, respectively, in men and 0.29, 0.32, and 0.23, respectively, in women. We found that all parameters were significantly associated with age in men and women. The SVA, TK, and PT increased with age, and LL decreased with age. Results of multiple regression analysis also demonstrated that the SVA, TK, and PI-LL are related to age. Indeed, the PI-LL value increased with age. In this study, a more excessive PI-LL mismatch was shown, indicating an increased risk of spinal malalignment. Differences in the absolute values of spino-pelvic parameters in each sex were small yet statistically significant. Thus, further study should be performed to corroborate this finding.


Characterization of papaya peptidase A as an enzyme of extreme basicity.
Papaya peptidase A, a papain-like enzyme, has formerly been shown to contain a larger excess of basic amino acids and to have a higher isoelectric point than any of the other enzymes in the papaya latex. Determinations of the free electrophoretic mobility as a function of pH now establishes the isoelectric point of papaya peptidase A as 11.7 and that of succinylated papaya peptidase A as 3.8. Although the specific activity of the enzyme appears only slightly affected by the succinylation, the accompanying change in the charge/mobility ratio seems to indicate a relatively large conformational change upon succinylation.


Differential effects of agonists on adenylyl cyclase superactivation mediated by the kappa opioid receptors: adenylyl cyclase superactivation is independent of agonist-induced phosphorylation, desensitization, internalization, and down-regulation.
Prolonged activation of opioid receptors followed by agonist removal leads to adenylyl cyclase (AC) superactivation. In this study, we examined in CHO cells stably expressing the human or rat kappa opioid receptor (hkor or rkor) whether agonists had differential abilities to induce AC superactivation and whether the hkor and rkor exhibited differential AC superactivation. Pretreatment of the hkor with (trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzeneacetamide methanesulfonate (U50,488H) induced AC superactivation in a time- and dose-dependent manner, reaching a plateau at 4 h and 0.1 microM. The extents of AC superactivation after a 4-h pretreatment of the hkor with saturating concentrations of agonists were in the order of the full agonists U50,488H, dynorphin A(1-17), (+/-)-ethylketocyclazocine, etorphine, and U69,593 > the high-efficacy partial agonist nalorphine > the low-efficacy partial agonists nalbuphine, morphine, and pentazocine. Interestingly, the full agonist levorphanol caused much lower AC superactivation than other full agonists and reduced the AC superactivation induced by U50,488H and dynorphin A(1-17) in a dose-dependent manner. The order of relative efficacies of agonists in causing AC superactivation mediated by the rkor was similar to that mediated by the hkor and the extents of AC superactivation were slightly lower. Because the rkor does not undergo U50,488H (1 microM)-induced phosphorylation, desensitization, internalization, and down-regulation in these cells, the degree of AC superactivation is independent of these processes. This is among the first reports to demonstrate that relative efficacies of agonists in causing AC superactivation generally correlated with those in activating G proteins and a full agonist reduced AC superactivation induced by another full agonist.


A giant ancient schwannoma mimicking an adnexal mass: Case report.
Ancient schwannoma is a rare tumor of the peripheral nerve sheath. As degenerative properties are defined histologically, it can be wrongly interpreted as malignant. The case presented here is of a giant ancient schwannoma with a pelvic retroperitoneal location, which was mimicking an adnexal mass. In the rarely seen cases in the retroperitoneum, it may reach very large dimensions.


RESIDENT IMPLEMENTATION OF THE 2007 ACC/AHA GUIDELINES ON PREOPERATIVE CARDIAC EVALUATION IN NON-CARDIAC SURGERY PATIENTS: IS CLINICAL EXPERIENCE ENOUGH?
Preoperative evaluation of surgical patients is important, as perioperative complications are associated with increased mortality. Specialties including anesthesiology, internal medicine, cardiology, and surgery are involved in the evaluation and management of these patients. This institutional study investigated the residents' knowledge of the 2007 American College of Cardiology/American Heart Association (ACC/AHA) guidelines on perioperative evaluation of patients undergoing non-cardiac surgery. This pilot study used a web-based survey questionnaire to assess resident's knowledge of the 2007 ACC/AHA guidelines through individual steps and corresponding branch point(s) in twelve clinical scenarios. Additionally, residents were asked if they were aware of, or if they had received lectures on ACC/AHA guidelines. Staff anesthesiologists with training in cardiac and intensive care medicine validated the scenarios. A total of 104 resident participants were surveyed including 35 anesthesiology residents, 41 internal medicine residents, 20 surgery residents, and 8 cardiology fellows. Awareness of the 2007 ACC/AHA guidelines by specialty was: anesthesiology (85%), internal medicine (97.6%), cardiology (100%), and surgery (70%). Only 54.3% of anesthesiology, 31.7% of internal medicine, 100% of cardiology, and 10% of surgery residents stated they received lectures. The overall mean score achieved on the eleven scenarios was 50.4% for anesthesiology, 47.0% for internal medicine, 55.7% for cardiology, and 42.3% for surgery. Although the majority of residents were aware of the 2007 ACC/AHA guidelines, fewer received lectures and regardless of specialty, implementation of these guidelines was poor. There exists significant room for improvement in the understanding of preoperative assessment of non-cardiac surgery patients.


Overcoming the Heat Transfer Paradox: Nano Ridges Induce "Pistol Bubbles" and Reverse the Boiling Curve.
To increase the boiling heat transfer limit, we disrupted the previously nonevaporating region and increased the vaporization activity of "inert" liquid molecules by introducing nano ridges on the boiling surface. This solved the paradox of no heat transfer occurring through the thinnest liquid film in boiling bubbles; thus, the internal heat transfer limit of the bubbles was exceeded. We found that vigorous boiling occurred immediately once the nonevaporating region was activated, and the bubble frequency increased by an order of magnitude, reaching 1186 Hz, which has not been previously reported. With an increase in heat flux, the boiling curve exhibited a "return". We achieved an extremely high bubble frequency by experimentally quantifying the major influence of nonevaporating region disruption on boiling heat transfer. The mechanism behind the generation of the ultrahigh-frequency bubbles was discovered. This study also reveals a new mechanism for the reversed boiling curve.


Is there a need for rescreening of patients treated for genital chlamydial infections?
The present communication reviews reasons to perform rescreening of chlamydia-infected persons. It brings up difficulties to differentiate between relapse and reinfection. Studies on follow-up of chlamydia-positive cases after therapy are reviewed. It also highlights reasons for therapeutic failure, like compliance, pharmacological factors, including poor bioavailability, wrong dose regimens, lack of adherence to drug intake, neglect of partner notification and concomitant therapy in consorts, possible development of resistance to drugs generally prescribed, false negative or false positive diagnostic tests and reinfection from extra-genital not 'cured' sites. The review points to the need to establish programmes for routine rescreening of chlamydia-infected persons.


Effect of juvenile hormone on vitellogenin gene expression in the fat body of burying beetles, Nicrophorus orbicollis.
In the burying beetles, Nicrophorus orbicollis, it is not clear the extent to which synthesis of Vitellogenin (Vg) is under hormonal control. Juvenile hormone (JH) and ovarian development increase rapidly upon discovery of a carcass, the necessary reproductive resource, but in its absence, treatment with JH does not accelerate ovarian development. Here we investigated the effect of manipulating JH titers on Vg gene expression in the fat bodies of newly eclosed and sexually mature females. Topical applications of the JH analogue methoprene at doses of 200, 300, and 400 microg of methoprene/g beetle to newly eclosed females resulted in up to a 5-fold increase in fat body Vg mRNA levels compared to acetone-treated control females. However, none of these increases were statistically significant. We also measured hemolymph Vg in females subjected to prolonged treatment with an intermediate dose of 300 microg of methoprene/g beetle and found no statistically significant increase in hemolymph Vg following treatment. There was, however, a significantly positive correlation between Vg mRNA and hemolymph Vg. Conversely, although injecting sexually mature females with fluvastatin (an inhibitor of JH biosynthesis in the corpora allata) at a dose of 40 microg/ beetle resulted in significantly decreased JH titers in treated females compared to saline-injected controls, Vg transcription rates were not affected. We suggest that in burying beetles, JH alone is not sufficient to upregulate the expression of the Vg genes and that other factors may be involved in regulating their vitellogenic cycle as well.


Persistence with oral naltrexone for alcohol treatment: implications for health-care utilization.
Concerns have been raised about patients' failure to persist in alcohol treatment. We examined prescriptions for oral naltrexone in a large, nationally distributed treatment population to identify characteristics and health-care utilization patterns associated with persistence. Data from the 2000-2004 MarketScan Commercial Claims and Encounters Database were used to identify patients with alcohol-related claims who were prescribed naltrexone. Analysis identified patient characteristics that predicted persistence with naltrexone (defined as having filled prescriptions for >or=80% of the 6-month treatment period) and its association to health-care utilization. Of 1138 patients, 162 (14.2%) were persistent in obtaining naltrexone. Non-persistent patients were significantly younger, more likely to be hourly employees and to live in an area with a lower median income, and less likely to be newly diagnosed with an alcohol-related disorder. Non-persistence in obtaining naltrexone was associated with significantly more intensive treatments, including inpatient detoxification, emergency room visits and hospitalizations. Over a 6-month period, 85.8% of patients who filled an initial prescription for naltrexone did not persist in obtaining the medication. Non-persistence was associated with significantly greater use of costly health-care services. Because the study was correlational, it is not possible to conclude that persistence reduced health-care costs, as patients with a better prognosis may have been more persistent. Research is needed to determine whether interventions that enhance persistence with naltrexone therapy improve treatment outcomes and reduce health-care costs.


Postoperative analgesic effects of epidural administration of neostigmine alone or in combination with morphine in ovariohysterectomized dogs.
To evaluate analgesic effects of epidurally administered neostigmine alone or in combination with morphine in dogs after ovariohysterectomy. Animals-40 healthy bitches. After acepromazine premedication, anesthesia was induced. Dogs randomly received 1 of the following 4 epidural treatments 30 minutes before ovariohysterectomy (n = 10/group): saline (0.9% NaCl) solution (control), morphine (0.1 mg/kg), neostigmine (10 microg/kg), or morphine-neostigmine (0.1 mg/kg and 10 microg/kg, respectively). Analgesia was assessed for 24 hours after surgery by use of a visual analogue scale (VAS; scale of 0 to 10) or numeric descriptive scale (NDS; scale of 0 to 24) and by the need for supplemental analgesia (morphine [0.5 mg/kg, IM] administered when VAS was > or = 4 or NDS was > or = 8). Significantly more control dogs (n = 8) received supplemental analgesia, compared with the number of neostigmine-treated dogs (1); no dogs in the remaining groups received supplemental analgesia. Compared with values for the control dogs, the NDS scores were lower for morphine-neostigmine-treated dogs (from 2 to 6 hours and at 12 hours) and for morphine-treated dogs (all time points). The NDS scores were lower for morphine-treated dogs at 3, 12, and 24 hours, compared with values for neostigmine-treated dogs. The VAS was less sensitive than the NDS for detecting differences among groups. Epidurally administered neostigmine reduced the use of supplemental analgesia after ovariohysterectomy in dogs. However, analgesic effects were less pronounced than for epidurally administered morphine or morphine-neostigmine. Adding neostigmine to epidurally administered morphine did not potentiate opioid-induced analgesia.


Differentiation of adipose-derived stem cells into Schwann-like cells: fetal bovine serum or human serum?
Access to autologous Schwann cells is limited due to lack of donor site and its difficult isolation and culture. Therefore, one of the possible ways to obtain to Schwann cells is to differentiate mesenchymal stem cells into glial pathway using various materials and protocols. The aim of this study was to compare the effects of fetal bovine serum and human serum on Schwann cell differentiation of adipose-derived stem cells to choose the best serum for use in future research. For this purpose, after isolation of human adipose-derived stem cells, it was characterized and differentiated into Schwann cell lineage using two protocols which one of them contained fetal bovine serum and the other human serum. At the end, morphological evaluation declared an increased detachment of cells in response to human serum. On the other side, immunocytochemistry showed that there was a significant increase in the number of cells expressing glial fibrillary acidic proteins and S100 in fetal bovine serum-treated group when compared to human serum-treated one (P<0.05). It was concluded that fetal bovine serum was more effective than allogeneic human serum in Schwann cell differentiation of adipose-derived stem cells.


Ferulic acid destabilizes preformed beta-amyloid fibrils in vitro.
Inhibition of the formation of beta-amyloid fibrils (fAbeta), as well as the destabilization of preformed fAbeta in the CNS, would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). We reported previously that curcumin (Cur) inhibits fAbeta formation from Abeta and destabilizes preformed fAbeta in vitro. Using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies, we examined the effects of ferulic acid (FA) on the formation, extension, and destabilization of fAbeta at pH 7.5 at 37 degrees C in vitro. We next compared the anti-amyloidogenic activities of FA with Cur, rifampicin, and tetracycline. Ferulic acid dose-dependently inhibited fAbeta formation from amyloid beta-peptide, as well as their extension. Moreover, it destabilized preformed fAbetas. The overall activity of the molecules examined was in the order of: Cur > FA > rifampicin = tetracycline. FA could be a key molecule for the development of therapeutics for AD.


Clostridium novyi type A infection: a sporadic fatal case.
Infection with type A Clostridium novyi is rare. We report the case of a previously healthy 31-y-old woman with no known risk factors who died suddenly with a necrotizing soft tissue infection. We compare this case with a simultaneous outbreak of this infection amongst Scottish IDUs (injecting drug users).


The socio-economic burden of snakebite in Sri Lanka.
Snakebite is a major problem affecting the rural poor in many of the poorest countries in the tropics. However, the scale of the socio-economic burden has rarely been studied. We undertook a comprehensive assessment of the burden in Sri Lanka. Data from a representative nation-wide community based household survey were used to estimate the number of bites and deaths nationally, and household and out of pocket costs were derived from household questionnaires. Health system costs were obtained from hospital cost accounting systems and estimates of antivenom usage. DALYs lost to snakebite were estimated using standard approaches using disability weights for poisoning. 79% of victims suffered economic loss following a snakebite with a median out of pocket expenditure of $11.82 (IQR 2-28.57) and a median estimated loss of income of $28.57 and $33.21 for those in employment or self-employment, respectively. Family members also lost income to help care for patients. Estimated health system costs for Sri Lanka were $ 10,260,652 annually. The annual estimated total number of DALYS was 11,101 to 15,076 per year for envenoming following snakebite. Snakebite places a considerable economic burden on the households of victims in Sri Lanka, despite a health system which is accessible and free at the point of care. The disability burden is also considerable, similar to that of meningitis or dengue, although the relatively low case fatality rate and limited physical sequelae following bites by Sri Lankan snakes means that this burden may be less than in countries on the African continent.


(2-Nitrophenyl)acetyl: a new, selectively removable hydroxyl protecting group.
The utility of the (2-nitrophenyl)acetyl (NPAc) group for the protection of hydroxyl functions is reported. (2-Nitrophenyl)acetates are readily prepared starting from the commercially available, inexpensive (2-nitrophenyl)acetic acid, and these esters are stable under a series of common carbohydrate transformations. The NPAc group can be removed selectively using Zn and NH(4)Cl without affecting a series of common protecting groups. This new protecting group is orthogonal with the commonly used tert-butyldimethylsilyl, levulinoyl, 9-fluorenylmethoxycarbonyl, naphthylmethyl, and p-methoxybenzyl groups.


Thermoset phenolic matrices reinforced with unmodified and surface-grafted furfuryl alcohol sugar cane bagasse and curaua fibers: properties of fibers and composites.
Composites based on phenolic matrices and unmodified and chemically modified sugar cane bagasse and curaua fibers were prepared. The fibers were oxidized by chlorine dioxide, mainly phenolic syringyl and guaiacyl units of the lignin polymer, followed by grafting furfuryl alcohol (FA), which is a chemical obtained from a renewable source. The fibers were widely characterized by chemical composition analysis, crystallinity, UV-vis diffuse reflectance spectroscopy, SEM, DSC, TG, tensile strength, and 13C CP-MAS NMR. The composites were analyzed by SEM, impact strength, and DMA. The SEM images and DMA results showed that the oxidation of sugar cane bagasse fibers followed by reaction with FA favored the fiber/matrix interaction at the interface. The same chemical modification was less effective for curaua fibers, probably due to its lower lignin content, since the reaction considered touches mainly the lignin moiety. The tensile strength results obtained showed that the fibers were partially degraded by the chemical treatment, decreasing then the impact strength of the composites reinforced with them. In the continuity of the present project, efforts has been addressed to the optimization of fiber surface modification, looking for reagents preferably obtained from renewable resources and for chemical modifications that intensify the fiber/matrix interaction without loss of mechanical properties.


Hydrogen alleviates cell damage and acute lung injury in sepsis via PINK1/Parkin-mediated mitophagy.
Multiple organ failure (MOF) is the main cause of early death in septic shock. Lungs are among the organs that are affected in MOF, resulting in acute lung injury. Inflammation is an important factor that causes immune cell dysfunction in the pathogenesis of sepsis. Autophagy is involved in the process of inflammation and also occurs in response to cell and tissue injury in several diseases. We previously demonstrated that hydrogen alleviated the inflammation-induced cell injury and organ damage in septic mice. The focus of the present study was to elucidate whether mitophagy mediates the inflammatory response or oxidative injury in sepsis in vitro and in vivo. Furthermore, we evaluated the role of mitophagy in the protective effects of hydrogen against cell injury or organ dysfunction in sepsis. RAW 264.7 macrophages induced by lipopolysaccharide (LPS) were used as an in vitro model for inflammation, and cecal ligation and puncture (CLP)-induced acute lung injury mice were used as an in vivo model for sepsis. The key protein associated with mitophagy, PTEN-induced putative kinase 1 (PINK1), was knocked down by PINK1 shRNA transfection in RAW 264.7 macrophages or mice. Hydrogen ameliorated cell injury and enhanced mitophagy in macrophages stimulated by LPS. PINK1 was required for the mitigation of the cell impairment in LPS-stimulated macrophages by hydrogen treatment. PINK1 knockdown abrogated the beneficial effects of hydrogen on mitophagy in LPS-stimulated macrophages. Hydrogen inhibited acute lung injury in CLP mice via activation of PINK1-mediated mitophagy. These results suggest that PINK1-mediated mitophagy plays a key role in the protective effects of hydrogen against cell injury in LPS-induced inflammation and CLP-induced acute lung injury.


One-step solid-phase extraction cleanup and fluorometric analysis of deoxynivalenol in grains.
A rapid, quantitative, inexpensive, efficient method was developed to determine deoxynivalenol (DON) in wheat, barley, corn, wheat middlings, wheat flour, bran, malted barley, and oats. Samples are ground and extracted with acetonitrile-water (86 + 14). A portion of the extract is cleaned up by passage through a MycoSep No. 225 column, evaporated to dryness, and derivatized with zirconyl nitrate and ethylenediamine in methanol. The resulting fluorescent derivative of DON is identified and quantitated with a calibrated fluorometer containing a broad wavelength pulsed xenon light source. This method quantitated DON concentrations from 0.5 to 50 ppm without dilution and was linear when applied to samples of noncontaminated wheat spiked at 0.5, 5, 10, 25, and 50 micrograms DON/g. Correlation coefficients of the method with LC for multiple analyses (n > or = 14 for each commodity) applied to wheat, corn, barley, wheat flour, and wheat middlings were 0.99, 0.99, 0.99, 0.93, and 0.98, respectively. Individual analyses were conducted in < 30 min, and 24 samples were analyzed in 2 h.


The Role of Context in the Implementation of Trauma-Focused Treatments: Effectiveness Research and Implementation in Higher and Lower Income Settings.
In recent years, the implementation of trauma-focused treatments has expanded across settings that vary widely in the availability of resources, infrastructure, and personnel. The present review aims to inform researchers, policy makers, trainers, and administrators about this diverse range of research. Taking a global health perspective, this review of effectiveness trials and implementation studies compares strategies used in high-income countries to those in low- and medium-income countries. A primary difference between studies in high-income and low- and medium-income countries is the relative emphasis placed on fidelity or adaptation. Adaptations used in low- and medium-income countries might offer useful ideas for increasing the portability, impact, and accessibility of evidence-based interventions in high-income countries.


Bubble-pen lithography: Fundamentals and applications: Nanoscience: Special Issue Dedicated to Professor Paul S. Weiss.
Developing on-chip functional devices requires reliable fabrication methods with high resolution for miniaturization, desired components for enhanced performance, and high throughput for fast prototyping and mass production. Recently, laser-based bubble-pen lithography (BPL) has been developed to enable sub-micron linewidths, in situ synthesis of custom materials, and on-demand patterning for various functional components and devices. BPL exploits Marangoni convection induced by a laser-controlled microbubble to attract, accumulate, and immobilize particles, ions, and molecules onto different substrates. Recent years have witnessed tremendous progress in theory, engineering, and application of BPL, which motivated us to write this review. First, an overview of experimental demonstrations and theoretical understandings of BPL is presented. Next, we discuss the advantages of BPL and its diverse applications in quantum dot displays, biological and chemical sensing, clinical diagnosis, nanoalloy synthesis, and microrobotics. We conclude this review with our perspective on the challenges and future directions of BPL.


Chromosome pulverization in virus-induced heterokaryons of mammalian cells from different species.
The phenomena of cell fusion and chromosome pulverization after inoculation with UV-inactivated Sendai virus were studied in mixed suspensions of cell lines from different mammalian species. Two cell combinations were used: the Chinese hamster cell line (Don) and RPMI 8226 (Simpson) cell line of human hematopoietic origin,and the Don and LLC-MK2 (MK) cell lines, the latter derived from monkey kidney cells. Each of the 3 cell lines had a high cell-fusion capacity when infected with the virus in homologous cultures. The heterokaryons of Don and Simpson cells were formed at lower frequency than homokaryons in either Don or Simpson cells, and heterokaryon formation between Don and MK cells was rare. The findings indicated that the cells used maintained some specificity of the cell surfaces. Chromosome pulverization was found in heterokaryons and was similar to that observed in homokaryons. The results confirmed further our presently held concept that cell fusion is a prerequisite for induction of pulverization, and also suggest that the possible role played by the mitotic nucleus with its cytoplasm in pulverization applies to the heterologous as well as to the homologous nuclei.


[Efficacy observation of cervical spondylosis treated with acupuncture at three lines of cervical Jiaji (EX-B 2)].
To compare the difference in the clinical efficacy on cervical spondylosis between acupuncture at three lines of cervical Jiaji (EX-B 2) and oral administration of jingfukang granules. Three hundred cases of cervical spondylosis were divided into an acupuncture group and a medication group, 150 cases in each one. In the acupuncture group, according to the different types of cervical spondylosis, acupuncture was applied at three lines of cervical Jiaji (EX-B 2), once a day. In the medication group, jingfukang granules were prescribed for oral administration, one bag each time, three times a day. The treatment of ten days made one session in the two groups and two sessions were required totally. Before and after two sessions of treatment, the clinical assessment scale for cervical spondylosis (CASCS) was adopted to evaluate the score of subjective symptoms, clinical physical signs and adaptability as well as the total score in the patients of the two groups and the efficacy was compared. The patients' symptoms and physical signs were alleviated, the adaptability was improved and the score of each item and the total score were increased in the two groups after treatment (all P<0.01). The improvements in the acupuncture group were better than those in the medication group (all P<0.01). The curative and markedly effective rate was 90.7% (136/150) in the acupuncture group, better than 66.0% (99/150) in the medication group (P<0.01). Acupuncture at three lines of cervical Jiaji (EX-B 2) achieves the significant clinical efficacy on cervical spondylosis. This therapy is superior to relieving symptoms and physical signs and recovering adaptability as compared with jingfukang granules.


Cactus Spine Wounds: A Case Report and Short Review of the Literature.
Cactus plants are commonly seen in arid southwestern regions of the United States. Due to their ready availability, they have become a popular houseplant. The spines or glochidia can easily puncture the skin with only minor pressure (ie, bumping or touching the cactus). Removal of the offending spine is difficult, even with tweezers. An 18-year-old woman initially self-removed the spines, and marked discomfort and intense erythematous reaction developed within 8 to 10 hours. Patient presented to the emergency room at Mercy Hospital and Trauma Center (Janesville, Wisconsin), where spine removal was unsuccessful. Following emergency room discharge, she had difficulty walking from pain and swelling and was advised to use heat packs, take amoxicillin/clavulanic acid, and rest with her leg elevated for another 7 days along with using eye drops for eye irritation. The lesions slowly improved over the next several months. The case of multiple barrel cactus spine injuries with severe pain and swelling is presented herein as well as a review of the treatment options and complications of cactus spine injuries.


Phospholipid activation of the insulin receptor kinase: regulation by phosphatidylinositol.
A soybean phospholipid mixture produced a concentration-dependent enhancement of beta subunit autophosphorylation of the detergent-soluble, purified human placental insulin receptor. Although phosphatidylcholine, phosphatidylethanolamine, or phosphatidylserine also increased insulin receptor autophosphorylation, only phosphatidylinositol (PtdIns) stimulated to a similar extent as the phospholipid mixture. The effect of PtdIns was biphasic, stimulating at low concentrations (75 microM), but having no stimulatory effect at high concentrations (1.0 mM). Phospholipids also stimulated the exogenous protein kinase activity of the insulin receptor toward histone H2B. Phosphorylation of PtdIns occurred with these purified insulin receptor preparations, but this activity was insulin-independent, and the turnover number for PtdIns phosphorylation in the presence of soybean phospholipid was 1/220th as small as the turnover number for the autophosphorylating activity. These results suggest that although PtdIns can modulate the activity of the insulin receptor kinase, PtdIns phosphorylation itself is not directly involved in this regulation.


Neurocognitive Deficits After Radiation Therapy for Brain Malignancies.
Radiotherapy (RT) has proven to be an effective therapeutic tool in treatment of a wide variety of brain tumors; however, it has a negative impact on quality of life and neurocognitive function. Cognitive dysfunction associated with both the disease and adverse effects of RT is one of the most concerning complication among long-term survivors. The effects of RT to brain can be divided into acute, early delayed, and late delayed. It is, however, the late delayed effects of RT that lead to severe neurological consequences such as minor-to-severe cognitive deficits due to irreversible focal or diffuse necrosis of brain parenchyma. In this review, we discuss current and emerging data regarding the relationship between RT and neurocognitive outcomes, and therapeutic strategies to prevent/treat postradiation neurocognitive deficits.


Decomposing socioeconomic inequalities in alcohol use by men living in South African urban informal settlements.
The prevalence of alcohol consumption among males living in urban settlements in South Africa is high. This paper aims to measure socioeconomic inequalities in alcohol use among men residing in informal settlements and also to examine the factors associated with inequality in alcohol use among men living in informal settlements. The study uses data from the 2016 Study of South African Informal Settlements. Multiple correspondence analysis is used to calculate a wealth index as a measure of socioeconomic status. The Erreygers concentration index is employed to quantify the degree of socioeconomic inequality in alcohol use and decomposition analysis is conducted to assess the factors associated with inequality in alcohol use by men of various age groups. There is a socioeconomic-related inequality in alcohol use in informal settlements that discriminates against poor men. Inequality is especially pronounced in the case of males aged 15-34 years and males aged 35-44 years. Wealth status makes the biggest contribution to socioeconomic inequality in alcohol use. The contribution of social determinants of health like marital status and employment status differ across age groups. Employment status contribute more to the alcohol use inequality among males aged 15-34 years while marital status contribute more to the alcohol use inequality among males aged 35-44 years. Being single substantially increases inequality in alcohol use. Inequality in alcohol use exists among both younger and older males and discriminate against the poor. Public policies aimed at promoting public health and the prevention of unhealthy behaviours should target younger and middle-aged men from socioeconomically disadvantaged groups. We also suggest policies that target single males in informal settlements.


Sarcoptic mange: a zoonotic ectoparasitic skin disease.
A 56-year old man attended the Dermatology Outpatients Department with the complaint of a localized, extremely itchy, erythematous papular lesion of acute onset on the ventral aspect of the right thigh. The patient was referred to the Microbiology Lab for the microscopic detection of the fungal elements. The KOH mount from the skin scrapings showed no fungal elements, but it showed the mites of Sarcopetes scabiei mange. The Sarcoptic Mange is noteworthy because of the fact that it is a zoonotic disease which can easily be passed on to humans. A close contact with infested pet dogs was considered as the main predisposing factor in this case. The response to the antiscabietic treatment was dramatic.


Reciprocal walking orthosis with composite material body brace: initial development.
Reciprocal walking orthoses are routinely used by thoracic lesion patients for ambulation using crutches. A primary reason for their prescription is to provide therapeutic benefit and improved independence. To achieve this, maximum efficiency of walking and acceptance of the device is necessary to promote long-term compliance. Lateral rigidity in the orthosis influences walking efficiency, but the structural properties of conventional techniques for producing a sufficiently rigid body brace makes them unattractive. Currently patients and clinicians are forced to choose between greater efficiency or cosmesis of the orthosis. Composite materials have the potential to permit the required rigidity in a structure that is less obtrusive. However, their material properties could lead to unsafe forms of failure unless suitable manufacturing methods are devised. It is therefore inappropriate to supply prototypes to patients for field evaluation until laboratory investigation of innovative production methods has ensured that the orthosis is safe. A production technique has been devised that is ostensibly suitable. Prototype body braces have been tested and have been shown to have improved structural properties and safe failure modes. A test programme implemented on a complete concept orthosis has confirmed that improved lateral rigidity can be achieved with a less obtrusive body brace, and that it will behave safely for long enough to permit field evaluation.


Screening of collapsed mouse urinary bladders by optical matched filtering.
The principles of optical matched filtering are applied to the problem of screening specimens of mouse urinary bladders that may exhibit hyperplasia or contain carcinomas resulting from the ingestion of controlled amounts of 2-acetylaminofluorene. The construction of the matched filter and the experimental procedure are optimized for a small group of specimens to the extent that thirteen of twenty-two normal specimens are correctly classified, and all fifteen of the abnormal specimens are correctly classified.


Developmental neurotoxicity and immunotoxicity of 2,4,6-tribromophenol in Wistar rats.
Pregnant Wistar rats were exposed to 2,4,6-Tribromophenol (TBP) by whole body inhalation (0, 0.03, 0.1, 0.3, 1.0 mg/m3, 24 hr/day, 7 days/weeks, from day 1 to 21 of gestation). Significant decreases in orientation reactions were noted at concentrations of 1.0 mg/m3 (p < 0.05) in the open field test. Nonsignificant trends (p > 0.05) toward decreased horizontal movement and emotionality in the open field and increased electrical impulse skin pain threshold (SPT) were observed. No significant exposure-related differences in the nonspecific immunological status (phagocytosis and blood anti-microbe activity) of pregnant rats were seen after the exposure. Preimplantation and postimplantation embryo losses were significantly increased in a dose-dependent manner and were seen in all treated groups except the lowest concentration (0.03 mg/m3) group. Signs of retarded fetal skeletal development and increased frequencies of visceral abnormalities were found at concentrations of 0.1 and 1.0 mg/m3. Significant effects were found for lower incisor eruption and ear unfolding at a concentration of 0.3 mg/m3. The grooming behavior of 30-day old male progeny was significantly less than control in all experimental groups. Grooming behavior in female subjects exposed to a concentration of 0.3 mg/m3 and emotionality in subjects exposed to a concentration of 1 mg/m3 were decreased significantly. At 60 days of age emotional reactions were significantly decreased in female subjects from the 0.03, 0.3 and 1.0 mg/m3 groups. SPT was significantly increased in the 1 mg/m3 group for both male and female pups. Thus, evidence of CNS depression influence of TBP both in maternal and offspring groups was found. The NOEL (No Observed Effect Level) for developmental neurotoxicity is thus < 0.03 mg/m3, and the NOEL for maternal neurotoxicity is 0.3 mg/m3. These results suggest that exposure to TBP for 24 hr/day throughout gestation may cause developmental neurotoxicity, embryotoxicity and fetotoxicity, but not immunotoxicity.


Theory-of-Mind Training Causes Honest Young Children to Lie.
Theory of mind (ToM) has long been recognized to play a major role in children's social functioning. However, no direct evidence confirms the causal linkage between the two. In the current study, we addressed this significant gap by examining whether ToM causes the emergence of lying, an important social skill. We showed that after participating in ToM training to learn about mental-state concepts, 3-year-olds who originally had been unable to lie began to deceive consistently. This training effect lasted for more than a month. In contrast, 3-year-olds who participated in control training to learn about physical concepts were significantly less inclined to lie than the ToM-trained children. These findings provide the first experimental evidence supporting the causal role of ToM in the development of social competence in early childhood.


Genomics made easier: an introductory tutorial to genome datamining.
Integrated genome databases--such as the UCSC, Ensembl and NCBI MapViewer databases--and their associated data querying and visualization interfaces (e.g. the genome browsers) have transformed the way that molecular biologists, geneticists and bioinformaticists analyze genomic data. Nevertheless, because of the complexity of these tools, many researchers take advantage of only a fraction of their capabilities. In this tutorial, using examples from medical genetics and alternative splicing, I describe some of the biological questions that can be addressed with these techniques. I also show why doing so typically is more effective than using alternative methods and indicate some of the resources available for learning more about the advanced capabilities of these powerful tools.


Strategies for Selecting Crosses Using Genomic Prediction in Two Wheat Breeding Programs.
The single most important decision in plant breeding programs is the selection of appropriate crosses. The ideal cross would provide superior predicted progeny performance and enough diversity to maintain genetic gain. The aim of this study was to compare the best crosses predicted using combinations of mid-parent value and variance prediction accounting for linkage disequilibrium (V) or assuming linkage equilibrium (V). After predicting the mean and the variance of each cross, we selected crosses based on mid-parent value, the top 10% of the progeny, and weighted mean and variance within progenies for grain yield, grain protein content, mixing time, and loaf volume in two applied wheat ( L.) breeding programs: Instituto Nacional de Investigación Agropecuaria (INIA) Uruguay and CIMMYT Mexico. Although the variance of the progeny is important to increase the chances of finding superior individuals from transgressive segregation, we observed that the mid-parent values of the crosses drove the genetic gain but the variance of the progeny had a small impact on genetic gain for grain yield. However, the relative importance of the variance of the progeny was larger for quality traits. Overall, the genomic resources and the statistical models are now available to plant breeders to predict both the performance of breeding lines per se as well as the value of progeny from any potential crosses.


Hyperhomocysteinemia due to pernicious anemia leading to pulmonary thromboembolism in a heterozygous mutation carrier.
Pulmonary thromboembolism is a life-threatening condition resulting mostly from lower extremity deep-vein or pelvic-vein thrombosis. A 46-year-old woman was admitted to hospital with pain on the right side of the chest and hemoptysis. On laboratory analysis, D-dimer level was elevated. Computed tomographic pulmonary angiography revealed intravascular filling defects due to thrombi in right lower lobe pulmonary segmental arteries. Screening for thrombophilic states was normal except for heterozygous mutations of both prothrombin and methylene tetrahydrofolate reductase (MTHFR 677) genes. Homocysteine level was high, and vitamin B12 level and serum ferritin level were reduced. Serum antiparietal antibody was positive, and therefore, pernicious anemia was diagnosed along with iron-deficiency anemia. After the diagnoses were established, enoxaparin followed by warfarin was started in addition to oral vitamin B12, pyridoxine, thiamine, folic acid, and ferroglycine sulfate supplementation. At the end of 8 weeks of the replacement therapy, vitamin B12, folate, and homocysteine levels and red cell volume were found to be normal, with complete resolution of the thrombus confirmed by repeat computed tomographic pulmonary angiography. We conclude that hyperhomocysteinemia due to vitamin B12 deficiency associated with pernicious anemia might have decreased the threshold for thrombosis. In addition, the presence of heterozygous prothrombin and methylene tetrahydrofolate reductase mutations might serve as synergistic cofactors triggering pulmonary thromboembolism.


Comparative effectiveness of aggressive intravenous fluid resuscitation with lactated Ringer's solution and rectal indomethacin therapy in the prevention of pancreatitis after endoscopic retrograde cholangiopancreatography: a double blind randomised controlled clinical trial.
There is growing evidence indicating the aggressive intravenous fluid resuscitation (IVFR) can decrease the rate of pancreatitis; however, to the best of our knowledge it has not been well studied in a post-endoscopic retrograde cholangiopancreatography (post-ERCP) setting. To compare the effects of aggressive IVFR and rectal indomethacin (RI) in preventing pancreatitis after ERCP. This is a double blind randomised controlled clinical trial on 186 patients undergoing ERCP in Ahvaz, Iran. The inclusion criteria were ERCP for standard clinical indications such as choledocholithiasis, bile duct leak, and biliary obstruction. The IVFR group (n = 62) received a bolus of 20 ml/kg of body weight lactated Ringer's solution (LRS) immediately after ERCP, followed by 3 ml/kg/h maintenance for 8 h. The RI group (n = 62) received 50 mg rectal indomethacin immediately before procedure and 12 h after ERCP. The control group (n = 62) did not receive any treatment. Post-ERCP pancreatitis in IVFR, rectal indomethacin, and control groups occurred in 8 (12.9%), 16 (25.8%), and 20 (32.3%) patients (p = 0.036). Pancreatic pain was reported in 13 (21%), 21 (33.9%), and 27 (43.5%) patients in the IVFR, RI, and control group (p = 0.046). The serum amylase level increased over 24 h after intervention in all three groups. The mean serum amylase level 8 h after intervention in the IVFR patients was lower than the RI and control groups. Intravenous fluid resuscitation with LRS was more effective in preventing post-ERCP pancreatitis in comparison to the rectal indomethacin and control group.