Projections from the reticular formation of the medulla, the spinal trigeminal and lateral reticular nuclei to the inferior olive.
Injections of tritiated L-leucine were placed in the reticular formation of the medulla, the spinal trigeminal and lateral reticular nuclei of cats and silver grain accumulations in the inferior olivary nucleus were demonstrated by autoradiography. Cells of the reticular formation located at the junction of nuclei reticularis magnocellularis and reticularis parvocellularis in the rostral medulla and within nucleus reticularis ventralis in the caudal medulla contribute four distinct projections to the olive. Three projections are distributed ipsilaterally in the caudal part of the medial accessory olive, at mid-level of the dorsal accessory olive and in the ventrolateral bend of the principal olive, at rostral levels. There is also a small controlateral projection to the caudal part of the medial accessory olive. the spinal trigeminal nucleus sends crossed projections to the rostral part of the dorsal accessory olive and adjacent ventral lamella as well as to the caudal part of the medial accessory olive. The lateral reticular nucleus sends an extensive ipsilateral projection to the caudal part of the medial accessory olive and provides a small contribution to the same subdivision, contralaterally. All these projections converge with other known afferents to the olive.


Testing the facsimile accommodation hypothesis.
Research has failed to find evidence for a genuineness effect: the idea that aesthetic experiences are better when looking at real artworks versus reproductions of those artworks. One common explanation for this lack of an effect is the facsimile accommodation hypothesis. This hypothesis states that people can "look past" the limitations of a reproduction, which obscures the effect. However, this hypothesis itself has never been tested. In the current paper, we therefore test the facsimile accommodation hypothesis. In Study 1 (N = 120) we found no evidence for the facsimile accommodation hypothesis: there was no difference between the non-accommodation (instructed to evaluate the artwork as it is presented on the screen), the accommodation condition (instructed to evaluate the artwork as they imagine it would look in real life), and the control condition (no instructions). Though the control and accommodation condition did not differ which would be in line with the facsimile accommodation hypothesis, neither differed from the non-accommodation condition which they should have if the facsimile accommodation hypothesis was correct. We substantiate these findings by a pre-registered replication study (Study 2, N = 205), using Bayes Factors as well as equivalence testing to provide evidence for a null-effect, again finding no evidence for the facsimile accommodation hypothesis and even finding substantial evidence in favor of the null-hypothesis. In sum, we conclude that there is no evidence for the facsimile accommodation hypothesis and that we need to consider alternative explanations in order to understand the lack of empirical evidence for the genuineness effect.


Enhanced quality of capacitated spermatozoa from oligoasthenozoospermic men after incubation in test yolk medium.
To improve artificially the quality of poor sperm samples to be used in assisted procreation procedures, Test Yolk Buffer (TYB) incubation effect was investigated. After adding the TYB procedure to the standard swim-up technique, a significant (P < 0.001) increase in spermatozoa velocity was observed, while the other seminal parameters were not affected. Three of 11 couples who had not had success after three intraperitoneal inseminations (IPI) with sperm prepared by the usual swim-up technique obtained pregnancies after IPI with TYB-incubated spermatozoa. These preliminary results suggest that TYB incubation for capacitated spermatozoa be employed in the assisted procreation strategies applied for male infertility.


Analytical comparison of absolute quantification strategies to investigate the insulin signaling pathway in fat cells.
So far, mass spectrometry-based targeted proteomics is the most sensitive approach to answer and address specific biological questions in an accurate and quantitative fashion. However, the data analysis design used for such quantification varies in the field leading to discrepancies in the reported values. In this study, different quantification strategies based on calibration curves were evaluated and compared. The best accuracy and coefficient of variation was achieved by ratio to ratio calibration curves. We applied the ratio to ratio quantification approach to analyze very low abundant insulin signaling proteins such as PIK3RA (0.10-0.93 fmol/μg), AKT1 (0.1-0.39 fmol/μg), and the insulin receptor (0.22-2.62 fmol/μg) in a fat cell model and demonstrated the adaptation of this pathway at different states of insulin sensitivity.


An experimental approach to the immuno-modulatory basis of host-parasite local adaptation in tapeworm-infected sticklebacks.
The evolutionary arms race of hosts and parasites often results in adaptations, which may differ between populations. Investigation of such local adaptation becomes increasingly important to understand dynamics of host-parasite interactions and co-evolution. To this end we performed an infection experiment involving pairs of three-spined sticklebacks and their tapeworm parasite Schistocephalus solidus from three geographically separated origins (Germany, Spain and Iceland) in a fully-crossed design for sympatric and allopatric host/parasite combinations. We hypothesized that local adaptation of the hosts results in differences in parasite resistance with variation in parasite infection rates and leukocyte activation, whereas parasites from different origins might differ in virulence reflected in host exploitation rates (parasite indices) and S. solidus excretory-secretory products (SsESP) involved in immune manipulation. In our experimental infections, sticklebacks from Iceland were more resistant to S. solidus infection compared to Spanish and German sticklebacks. Higher resistance of Icelandic sticklebacks seemed to depend on adaptive immunity, whereas sticklebacks of German origin, which were more heavily afflicted by S. solidus, showed elevated activity of innate immune traits. German S. solidus were less successful in infecting and exploiting allopatric hosts compared to their Icelandic and Spanish conspecifics. Nevertheless, exclusively SsESP from German S. solidus triggered significant in vitro responses of leukocytes from naïve sticklebacks. Interestingly, parasite indices were almost identical across the sympatric combinations. Differences in host resistance and parasite virulence between the origins were most evident in allopatric combinations and were consistent within origin; i.e. Icelandic sticklebacks were more resistant and their S. solidus were more virulent in all allopatric combinations, whereas German sticklebacks were less resistant and their parasites less virulent. Despite such differences between origins, the degree of host exploitation was almost identical in the sympatric host-parasite combinations, suggesting that the local evolutionary arms race of hosts and parasites resulted in an optimal virulence, maximising parasite fitness while avoiding host overexploitation.


EpOMEs act as immune suppressors in a lepidopteran insect, Spodoptera exigua.
Epoxyoctadecamonoenoic acids (EpOMEs) are epoxide derivatives of linoleic acid (9,12-octadecadienoic acid) and include 9,10-EpOME and 12,13-EpOME. They are synthesized by cytochrome P450 monooxygenases (CYPs) and degraded by soluble epoxide hydrolase (sEH). Although EpOMEs are well known to play crucial roles in mediating various physiological processes in mammals, their role is not well understood in insects. This study chemically identified their presence in insect tissues: 941.8 pg/g of 9,10-EpOME and 2,198.3 pg/g of 12,13-EpOME in fat body of a lepidopteran insect, Spodoptera exigua. Injection of 9,10-EpOME or 12,13-EpOME into larvae suppressed the cellular immune responses induced by bacterial challenge. EpOME treatment also suppressed the expression of antimicrobial peptide (AMP) genes. Among 139 S. exigua CYPs, an ortholog (SE51385) to human EpOME synthase was predicted and its expression was highly inducible upon bacterial challenge. RNA interference (RNAi) of SE51385 prevented down-regulation of immune responses at a late stage (> 24 h) following bacterial challenge. A soluble epoxide hydrolase (Se-sEH) of S. exigua was predicted and showed specific expression in all development stages and in different larval tissues. Furthermore, its expression levels were highly enhanced by bacterial challenge in different tissues. RNAi reduction of Se-sEH interfered with hemocyte-spreading behavior, nodule formation, and AMP expression. To support the immune association of EpOMEs, urea-based sEH inhibitors were screened to assess their inhibitory activities against cellular and humoral immune responses of S. exigua. 12-(3-adamantan-1-yl-ureido) dodecanoic acid (AUDA) was highly potent in suppressing the immune responses. The addition of AUDA to a pathogenic bacterium significantly increased bacterial pathogenicity by suppressing host immune defense. In sum, this study demonstrated that EpOMEs play a crucial role in facilitating anti-inflammatory responses in S. exigua.


Application of main component fraction collection method for purification of compound libraries.
In order to support high-throughput library purification, a novel UV triggered fraction collection method was developed in which a maximum-seeking-algorithm-driven, six-port valve collects the largest chromatographic peak. This straightforward strategy achieves the one sample-one fraction approach, thus resulting in a simpler and less error prone workup procedure. The effectiveness of this main component fraction collection method will be illustrated here by the results of the purification of compound libraries (altogether 6086 compounds, having an averaged success rate of 79.4%). Advanced applications, where the desired component differs from the main component, will also be discussed.


Use of fertility drugs in Denmark 1973-1993. An analysis based on sale statistics.
The increasing use of drugs for ovarian stimulation and the possibility of long-term risks has actualized a quantitative assessment of the use of such therapy. The aim of the study was to analyze the development in the sale of different types of drugs used for ovarian stimulation in Denmark during the last two decades. Sale statistics of clomiphene citrate, cyclophenile, human menopausal gonadotropin (hMG), mare menopausal gonadotropin (mMG) and human chorionic gonadotropin (hCG) in Denmark 1973-1993. The number of defined daily doses (DDD) was calculated for each product group. On given assumptions the number of cycles of different treatment regimens and the number of treated women was calculated. The sale has increased almost exponentially throughout the last two decades: Clomiphene citrate 11 fold, hMG 30 fold, and hCG 5 fold. Today, among women 15-44 years old, the estimated incidence rate of women treated with clomiphene alone is about 2.7/1,000/year, and the incidence rate of women treated with clomiphene/hCG and hMG/hCG account for about 3.1/1,000/year and 1.9/1,000/year, respectively. Any study concerning short- and long-term effects of ovarian stimulation have to consider this secular trend.


Intestinal and systemic effects of oral insulin supplementation in rats after weaning.
Oral insulin has intestinal trophic effects in suckling animals. In mice, lower glucose and lipid levels may be seen when oral insulin is given after the weaning period. The purpose of the present study is to examine local and systemic effects of oral insulin supplementation in rats in the postweaning period. Immediately after weaning, Sprague-Dawley rats received either drinking water (controls) or oral insulin in their drinking water (1 U/ml) for either 1 week or 6 weeks. Intestinal mucosal parameters (bowel and mucosal weight, mucosal DNA and protein) and histological changes were examined in all study groups. Glucose levels were monitored weekly, and at the end of the study, blood levels of glucose, lipids, and insulin were measured in the fasting state. After 1 week of insulin supplementation, mucosal weight in duodenum and jejunum as well as jejunal DNA content were significantly higher in insulin-supplemented rats compared to controls. Duodenal circumference and villus height in jejunum were significantly higher in insulin-supplemented rats compared to controls on both day 7 and day 42. Total cholesterol levels were significantly lower in the study group compared with the controls. We conclude that oral insulin supplementation exerts intestinal trophic effects, as well as systemic effects in the postweaning period in rats.


Trend and Economic Burden of Intravenous Narcotic Analgesic Utilization in Major Vascular Interventions in the United States.
The use of IV narcotic analgesics (IVNA) within the context of vascular procedures is not fully described. We sought to evaluate the burden of IVNA including narcotic analgesia-related adverse drug events (NARADE), associated mortality and hospitalization cost in open and endovascular vascular procedures, and to compare it with nonnarcotic analgesia (IVNNA). Retrospective cross-sectional study in hospitals participating in Premier database (2009-2015). Logistic regression analysis was implemented to report the risks of NARADE and in-hospital mortality. Negative binomial regression was used to assess length of stay and generalized linear modeling was used to estimate the hospitalization cost. A total of 171,473 patients were identified. NARADE occurred in 6.2% of the cohort. NARADE group was similar in gender and race but was slightly older (median age 71 vs. 70; P < 0.001). After risk-adjustment, NARADE risk was higher in patients who received IVNA-alone in carotid and lower extremity revascularization (LER) [OR (odds ratio) (95% confidence interval [CI]): 1.17 (1.02-1.34) and 1.31 (1.14-1.50)] or combined with IVNNA [OR (95% CI): 1.34 (1.13-1.59) and 1.81 (1.54-2.13)], respectively. Patients receiving aortic repair benefited from the use of IVNA + IVNNA [OR (95% CI): 0.82 (0.69-0.98)]. Occurrence of NARADE doubled the LOS, amplified mortality risk and increased cost in all domains. NARADE increased the odds of mortality by 24.3, 6.5 (4.9-8.68) and 16.6 times and added $5,368, $12,737 and $11,349 to the cost of carotid, aortic and LER interventions, respectively. In contrast, IVNNA was not associated with NARADE risk, increased LOS or cost and showed a survival benefit in patients undergoing open aortic repair [aOR (95% CI): 0.52 (0.36-0.75)]. The use of opioid-based narcotics had increased the risk of NARADE, resources utilization and NARADE-related mortality. Yet the use of nonopioid-based analgesic was safe, did not increase the cost and reduced mortality in open AA repair. This entices shifting the paradigm toward exploring nonopioid-based analgesia options in order to replace or minimize opioid requirements.


Temperature dependence of monovalent cation fluxes in isolated rat hearts: a magnetic resonance study.
Ion flux studies were performed on Langendorff-perfused rat hearts using 87Rb, 7Li and 23Na NMR at 36, 20 and 10 degreesC, and at constant extracellular pH (7.40). Using 31P NMR, the intracellular pH was estimated and the high energy phosphate content monitored. Compared to 36 degreesC (k=0.044+/-0.015 min-1), our measurements showed incomplete Rb+ efflux with a dramatically (5-fold) increased rate constant, k, at 20 degreesC, k=0.238+/-0.080 min-1. 5 microM glibenclamide, a KATP-channel inhibitor, completely depressed the hypothermia-activated Rb+ efflux at this temperature (k=0.052+/-0. 018 min-1). 7Li NMR efflux studies on KCl-arrested hearts at 20 degreesC also showed an increase (3-fold) in efflux rate constant: k=0.090+/-0.003 min-1 relative to its value at 36 degreesC. At 10 degreesC, both Rb+ and Li+ showed efflux rate constants similar to those observed at 36 degreesC, k=0.071+/-0.016 min-1 and k=0.050+/-0. 005 min-1, respectively, and the washout was complete. 31P NMR at 36, 20 and 10 degreesC indicated cytosolic alkalinization at pH values of 7.05, 7.21 and 7.40, respectively. The ion transport data could be interpreted in terms of a myocyte model allowing for temperature-dependent changes in transport coefficients. The incomplete efflux of Rb+ at 20 degreesC may indicate the existence of a mitochondrial Rb+-pool with a very low Rb+ permeability for efflux. These findings correlate with previously observed membrane phase transitions in these systems.


T-Tests: The BMI Study Continues.
Medical directors may be asked to analyze their company's experienced laboratory results. This practical research note explores the use of the statistical programming language R for analysis. Use of the two different t-tests available in R (unpaired and paired) is explained.


Effect of cyproterone acetate, levonorgestrel and progesterone on adrenal glands and reproductive organs in the beagle bitch.
The effects of short-term (8 weeks) treatment with different doses of cyproterone acetate (CPA), levonorgestrel (LN) and progesterone (PRO) on the adrenal gland, ovary, uterus and vagina were studied in cycle-synchronised beagle bitches (first anoestrus). The same organs from non-treated primiparous beagle bitches at the 6th and 9th weeks of pregnancy were also included. In the animals treated with the highest doses of CPA (4.0 mg/kg/day orally) and PRO (42.5 mg/kg/day subcutaneously), as well as in pregnant bitches (9th week of pregnancy), a decrease in adrenal weight and cortex width and also an apparent loss of cells in the zona fasciculata and zona reticularis were observed. A marked increase in ovarian weight was recorded only in pregnant bitches (6th week of pregnancy). This was reflected by the presence of multiple well-developed corpora lutea. The ovaries of virgin control and progestagen-treated bitches revealed ovarian atrophy. Progestagen treatment caused marked stimulation of the uterus, resulting in dose-related oedematous and hyperplastic changes. Comparable findings were also observed during pregnancy. The vaginal epithelium of the progestagen-treated and pregnant bitches showed marked mucification as compared with control bitches. These structural responses indicate that progestagen treatment stimulates a pseudopregnancy-like condition in the adrenal glands, uterus and vagina of the beagle bitch.


Posterior cordectomy. Our experience.
Several surgical procedures have been proposed for the treatment of respiratory distress secondary to bilateral cord palsy. We performed a retrospective study of our experience in posterior cordectomy with a laser CO(2), analysing the improvement of dyspnoea and voice quality after surgery. This was a retrospective study of 13 cases (9 female, 4 male). The age range was 25-79 years. Iatrogenic post-thyroidectomy (4 cases) was the most common aetiology of bilateral laryngeal palsy in our study. We assessed the subjective improvement of respiratory function and voice quality after laser surgery using the Spanish adaptation of the Voice Handicap Index (VHI). Dyspnoea improved in all patients. Two cases had a worsening of dyspnoea in the immediate postoperative period and one case was successfully solved with a new surgical intervention. After surgery, most of patients suffered from mild or middle dysphonia. The posterior cordectomy is an easy, safe and effective treatment for dyspnoea secondary to bilateral laryngeal palsy, maintaining acceptable voice quality.


Health care and socioeconomic impact of falls in the elderly.
Elderly falls are associated with long hospital stays, major morbidity, and mortality. We sought to examine the fate of patients ≥75 years of age admitted after falls. We reviewed all fall admissions in 2008. Causes, comorbidities, injuries, procedures, mortality, readmission, and costs were analyzed. Seven hundred eight patients ≥75 years old were admitted after a fall, with 89% being simple falls. Short-term mortality was 6%. Male sex, atrial fibrillation, acute myocardial infarction, congestive heart failure (CHF), intracranial hemorrhage, hospital-acquired pneumonia, trigger events, Clostridium difficile, and intubation were predictors of death (P < .05). Thirty-day readmission occurred in 14%; CHF, craniotomy, and acute renal failure were predictive. The median cost of hospitalization was $11,000 with cardiac disease, anemia, major orthopedic and neurosurgical procedures, pneumonia, and intubation as predictive. Simple falls in the elderly have high morbidity, mortality, and costs. Methodologies for prevention are warranted and should be studied intensively.


Treatment of gustatory sweating (Frey's syndrome) with botulinum toxin A.
Gustatory sweating is a common complication of parotid surgery. Injection of botulinum toxin A has been reported as a safe and effective treatment option for patients with Frey's syndrome. A total of 69 patients who had undergone superficial parotidectomy because of adenoma were evaluated with respect to the incidence of Frey's syndrome and treatment interest. Minor's iodine starch test was used to detect the affected skin area. Affected skin areas were documented using a digital camera; skin areas were evaluated morphometrically. A single injection of Botox per 1 cm(2) skin field was administered to those patients interested in treatment. Of 43 patients (62%) with gustatory sweating, 33 patients requested treatment. The affected skin area varied from 16 cm(2) to 81 cm(2). The individual Botox dosage ranged from 16 to 80 IU. All relevant clinical symptoms of sweating disappeared within 1 week after a single injection. Treatment was well tolerated with no side effects. Botox A injection is a safe and effective treatment with long-lasting effects for patients with extensive gustatory sweating.


Pedicle streaking: A novel and simple aid in pedicle positioning in free tissue transfer.
The pedicle positioning in free tissue transfer is critical to its success. Long thin pedicles are especially prone to this complication where even a slight twist in the perforator can result in flap loss. Pedicles passing through the long tunnels are similarly at risk. Streaking the pedicle with methylene blue is a simple and safe method which increases the safety of free tissue transfer. Once the flap is islanded on the pedicle and the vascularity of the flap is confirmed, the pedicle is streaked with methylene blue dye at a distance of 6-7 mm. The streaking starts from the origin of the vessels and continued distally on to the under surface of flap to mark the complete course of the pedicle in alignment. The presence of streaking in some parts and not in rest indicates twist in the pedicle. Four hundred and sixty five free flaps have been done at our centre in the last 5 years. The overall success rate of free flaps is 95.3% (22 free flap failures). There has not been a single case of pedicle twist leading to flap congestion and failure. This simple and novel method is very reliable for pedicle positioning avoiding any twist necessary for successful free tissue transfer.


In vitro modulation of intracellular receptor signaling and cytotoxicity induced by extracts of cyanobacteria, complex water blooms and their fractions.
The biological activity of cyanobacteria and their chemical components have been widely studied due to their blooms in eutrophic waters worldwide. The primary goal of this study was to determine if individual cyanobacterial species and mixtures of cyanobacteria collected from the environment contain compounds with the potential for interaction with signaling pathways of the aryl hydrocarbon receptor (AhR), androgen receptor (AR), estrogen receptor (ER), glucocorticoid receptor (GR) and retinoid acid receptor (RAR). Cytotoxicity and specific toxic potencies of products of freshwater cyanobacteria were determined by use of in vitro reporter gene trans-activation assays. The testing included samples prepared from five selected single cyanobacterial species cultivated in laboratory and five complex cyanobacterial biomasses collected from blooms in surface waters in the Czech Republic. The results demonstrate estrogenic potencies of extracts of cyanobacterial biomasses. Among the laboratory single species, the extract of Planktothrix agardhii (intracellular metabolites) had a potency of estrogenic equivalents (EEQ) of 3.8 ng 17β-estradiol/g dw. The estimates of EEQs of samples prepared from complex cyanobacterial biomasses collected from freshwaters in the Czech Republic ranged from 19 to 2200 ng 17β-estradiol/g dw. Several samples prepared from the environmental cyanobacterial biomasses potentiated the androgenic potency of dihydrotestosterone. There was no dioxin-like, glucocorticoid or anti/retinoic activity observed for any of the extracts studied. Extracts of natural complex cyanobacterial biomasses exhibited greater and more frequent presence of compounds with specific modes of action, mainly estrogenic, and also greater cytotoxicity than extracts of single cyanobacterial species. The demonstrated estrogenic potency of the compounds present in complex cyanobacterial biomasses is of environmental relevance, and could potentially contribute to endocrine disruptive effects in aquatic ecosystems in case of great bloom densities.


Focus on Adolescent Use of Club Drugs and "Other" Substances.
Club drugs and "other" abusable substances are briefly overviewed as a reminder about the wide variety of known and unknown substances used by adolescents, the high potential for direct and interactive substance use effects to manifest acutely and chronically, and the vigilance needed to anticipate and recognize the new effects and drug-drug interactions arising as novel substances continue to be custom "designed," manufactured, and marketed to meet substance use trends. This article discusses dextromethorphan, flunitrazepam (Rohypnol), gamma-hydroxybutyrate, inhalants, ketamine, lysergic acid diethylamide, methylenedioxymethamphetamine, phencyclidine, Salvia divinorum (salvia), synthetic cannabinoids, and synthetic cathinones (bath salts).


Dermoid Cyst of the Parotid Gland: A Rare Entity.
Dermoid cysts of the head and neck are a rare entity. These cysts are benign cystic malformations and histologically composed of tissues originating from ectoderm and mesoderm. Dermoid cysts usually presents as midline neck mass and rarely appear in lateral region. These are extremely rare in parotid gland, however should be considered as a differential in the list of parotid mass. There are a few cases published till date. Superficial parotidectomy is suggested as surgical treatment, however sometimes enucleation is also sufficient. There are only very few case reports published on dermoid cysts in parotid glands. We present a rare case of this entity and the challenges faced in making diagnosis with a short review of the literature.


Are synucleinopathies prion-like disorders?
A shared neuropathological feature of idiopathic Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy is the development of intracellular aggregates of α-synuclein that gradually engage increasing parts of the nervous system. The pathogenetic mechanisms underlying these neurodegenerative disorders, however, are unknown. Several studies have highlighted similarities between classic prion diseases and these neurological proteinopathies. Specifically, identification of Lewy bodies in fetal mesencephalic neurons transplanted in patients with Parkinson's disease raised the hypothesis that α-synuclein, the main component of Lewy bodies, could be transmitted from the host brain to a graft of healthy neurons. These results and others have led to the hypothesis that a prion-like mechanism might underlie progression of synucleinopathy within the nervous system. We review experimental findings showing that misfolded α-synuclein can transfer between cells and, once transferred into a new cell, can act as a seed that recruits endogenous α-synuclein, leading to formation of larger aggregates. This model suggests that strategies aimed at prevention of cell-to-cell transfer of α-synuclein could retard progression of symptoms in Parkinson's disease and other synucleinopathies.


Stimulation of hepatic lipogenesis by eicosa-5,8,11,14-tetraynoic acid in mice fed a high linoleate diet.
Liver slices, from mice fasted for one day and then refed for three days either a 15% corn oil diet or a 15% corn oil diet containing eicosa-5,8,11,14-tetraynoic acid (TYA), were incubated with [1-14C] acetate or [3H] H2O to determine lipogenic capacity. Dietary TYA produced a twofold stimulation in fatty acid and cholesterol synthesis. TYA also caused an increase in the relative proportion of linoleate (C18:2) and a decrease in that of arachidonate (C20:4) in liver. Thus, (a) despite high levels of C18:2, hepatic lipogenesis can be increased, and (b) even short term feeding of TYA can alter the hepatic fatty acid composition presumably by inhibition of arachidonate synthesis from linoleate.


Acidic phosphoproteins associated with the host erythrocyte membrane of erythrocytes infected with Plasmodium berghei and P. chabaudi.
New phosphoproteins appear on the host erythrocyte membrane during Plasmodium berghei and P. chabaudi infection. Distinct proteins having similar properties and all distinguished by isoelectric points of less than 4.0 are identified. Associated with the erythrocyte membranes of P. berghei infected erythrocytes are two proteins with molecular masses of 65 and 46 kDa, whereas 93, 90 and 76 kDa proteins are observed during P. chabaudi infection. These new erythrocyte membrane associated proteins are all of parasite origin as indicated by metabolic labeling with proline and are synthesized during the ring stage of the asexual replicative cycle. Three of these proteins, the 93 kDa P. chabaudi protein and both P. berghei proteins, have been purified and the amino acid composition determined. All three are characterized by a relatively high proportion of aspartate and glutamate residues. Mono-and polyclonal antibodies were also raised against the same three purified proteins. No cross reactivity between these three proteins is observed, but one monoclonal antibody against the 65 kDa P. berghei crossreacts with a 27 kDa mouse erythrocyte protein. Immunofluorescence using the antibodies in combination with subcellular fractionation studies clearly shows that these phosphoproteins are associated with the host erythrocyte membrane and not the parasite.


A comprehensive patient care system for the family practice.
Family and Community Health Associates (FACHA) has incorporated an in-house, on-line computerized medical information system into a two-office, three-physician family practice medicine group. A Basic Four System 610 minicomputer is utilized to store all the medical, pharmaceutical, financial, and scheduling records. A SOAP-formated encounter form is used to collect the data. Five medical reports are printed prior to each patient encounter. Evaluations of the use and the benefits of this system are presented. A cost study, which calculated the cost of maintaining a computer-stored patient record, showed that a patient record could be updated and maintained for $1.32. A quality of care evaluation revealed that the preaudit of the computer-generated medical reports increased patient compliance to health maintenance suggestions. Another quality of care evaluation revealed that computer-generated flow charts did not significantly improve the diastolic blood pressure value of chronic hypertensive patients.


Comparison of three massively parallel sequencing platforms for single nucleotide polymorphism (SNP) genotyping in forensic genetics.
Three MPS platforms are being used in forensic genetic analysis, i.e., MiSeq FGx, Ion S5 XL, and MGISEQ-2000. However, few studies compared their performance. In this study, we sequenced 83 common SNPs of 71 samples using the ForenSeq™ DNA Signature Prep Kit on MiSeq FGx, the Precision ID Identity Panel on Ion S5 XL, and the MGIEasy Signature Identification Library Prep Kit on MGISEQ-2000 and then the performance was compared. Results showed that the MiSeq FGx had the highest sequence quality but the lowest sequencing depth and allele balance. Discordant genotypes were observed at six SNPs, which may be caused by variants at primer binding regions, indel errors, or misalignments. Besides, two kinds of background noises, allele-specific miscalled reads (ASMR) and allele-nonspecific miscalled reads (ANMR), were characterized. MGISEQ-2000 showed the highest level of ASMR while Ion S5 XL had the highest level of ANMR. Site- and genotype-dependent miscalled patterns were observed at several SNPs on Ion S5 XL and MGISEQ-2000, but few on MiSeq FGx. In conclusion, the three MPS platforms perform differently with respect to sequencing quality, sequencing depth, allele balance, concordance, and background noise. These findings may be useful for data comparison, mixture deconvolution, and heteroplasmy analysis in forensic genetics.


Randomized trial comparing overnight preoperative fasting period Vs oral administration of apple juice at 06:00-06:30 am in pediatric orthopedic surgical patients.
We aimed to evaluate the efficacy of clear liquids orally administered at 06:00-06:30 am on the morning of surgery to reduce prolonged preoperative fasting periods. After obtaining informed parental consent, 100 children undergoing scheduled orthopedic surgical procedures, ASA I-II, were randomly allocated to two groups. In group 1, children underwent the typical overnight preoperative period and patients in group 2 received a commercial brand of apple juice (glucose 28 g in 250 ml) at 06:00-06:30 am on the day of surgery. Patients <3 years old received 15 ml.kg(-1) and older children 10 ml.kg(-1) to a maximum volume of 250 ml. All patients underwent overnight fasting for milk and solids. Fasting time was 4.8 +/- 2.1 h (ranging from 3 to 11 h) in the group receiving apple juice at 06:00-06:30 am and 13.2 +/- 3.3 h (ranging from 5 to 19 h) in the overnight-fasting group (P < 0.05; 95% CI: -9.6 to -7.4 h). More patients were irritable (odds ratio, OR 4.5; 95% CI: 1.9-10.8) and dehydrated (OR 21.6; 95% CI: 5.9-79.0) in the overnight-fasting group. Glucose levels <2.7 mmol.l(-1) (50 mg.dl(-1)) were not reported in any case. A 15 ml.kg(-1) of apple juice for patients of <3 years of age or 10 ml.kg(-1) for older children, at 06:00-06:30 am of the surgical morning is a simple procedure to prevent dehydration and to produce positive behavior in low-risk, pediatric surgical patients.


Monitoring RNA restructuring in a human cell-free extract reveals eIF4A-dependent and eIF4A-independent unwinding activity.
The canonical DEAD-box helicase, eukaryotic initiation factor (eIF) 4A, unwinds 5' UTR secondary structures to promote mRNA translation initiation. Growing evidence has indicated that other helicases, such as DHX29 and DDX3/ded1p, also function to promote the scanning of the 40S subunit on highly structured mRNAs. It is unknown how the relative contributions of eIF4A and other helicases regulate duplex unwinding on an mRNA to promote initiation. Here, we have adapted a real-time fluorescent duplex unwinding assay to monitor helicase activity precisely in the 5' UTR of a reporter mRNA that can be translated in a cell-free extract in parallel. We monitored the rate of 5' UTR-dependent duplex unwinding in the absence or presence of an eIF4A inhibitor (hippuristanol), a dominant negative eIF4A (eIF4A-R362Q), or a mutant eIF4E (eIF4E-W73L) that can bind the m7G cap but not eIF4G. Our experiments reveal that the duplex unwinding activity in the cell-free extract is roughly evenly split between eIF4A-dependent and eIF4A-independent mechanisms. Importantly, we show that the robust eIF4A-independent duplex unwinding is not sufficient for translation. We also show that the m7G cap structure, and not the poly(A) tail, is the primary mRNA modification responsible for promoting duplex unwinding in our cell-free extract system. Overall, the fluorescent duplex unwinding assay provides a precise method to investigate how eIF4A-dependent and eIF4A-independent helicase activity regulates translation initiation in cell-free extracts. We anticipate that potential small molecule inhibitors could be tested for helicase inhibition using this duplex unwinding assay.


High performance liquid chromatographic determination of serum UV profiles of normal subjects and patients with breast cancer and benign fibrocystic changes.
High performance liquid chromatography (HPLC) was used to determine the UV profiles of serum samples taken postoperatively from 22 patients with histologically documented breast cancer, 8 patients with benign breast fibrocystic changes and 10 normal subjects. The analyses were performed on coded serum samples and after they were completed, the code was broken and the results correlated with the clinical data. Only one ml of serum was required for the HPLC analysis and identification. Detection limits for the nucleosides and bases were in the 10--20 pmol range and the injection volume of the deproteinated serum was 75 mul. The UV profiles of the normal subjects were very reproducible and similar to those of the patients with benign fibrocystic changes. The profiles of some of the cancer patients were distinctly different from the two other groups, 1-methylinosine and N2-methylguanosine, which were not detected in sera from normal subjects and patients with benign fibrocystic changes, were found in 45.5% and 22.7% of the cancer patients, respectively. Patients with the metastatic disease also showed elevated levels of guanosine and uridine. Only one false positive was found in the normal population. At present, it is not clear whether this indicates a subclinical manifestation of the disease and it must await further follow-up.


Attentional Mechanisms in Autism, ADHD, and Autism-ADHD Using a Local-Global Paradigm.
Cognitive flexibility or attentional set-shifting capacity has long been considered a core area of executive dysfunction for individuals with autism. Whether these difficulties are due to higher-level attentional difficulties associated with comorbid ADHD remains unclear. The current study compared the performance of 48 participants with autism, ADHD, autism-ADHD, and a comparison group ( N = 12 per group) on a set-shifting task, which included a local-global paradigm. Results of this study revealed that participants with attentional difficulties (autism + ADHD and ADHD alone) exhibited a significant shifting cost (difference between maintaining and shifting attention). Attentional difficulties associated with ADHD may be associated with an enhanced attentional shifting cost. Implications of these results were discussed in relation to screening for ADHD symptoms in studies of individuals with autism which seek to determine the neuropsychological profile of this condition.


Visible light photocatalytic degradation of dyes by bismuth oxide-reduced graphene oxide composites prepared via microwave-assisted method.
Bi2O3-reduced graphene oxide (RGO) composites were successfully synthesized via microwave-assisted reduction of graphite oxide in Bi2O3 precursor solution using a microwave system. Their morphologies, structures, and photocatalytic performance in the degradation of methylene blue (MB) and methyl orange (MO) were characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction spectroscopy, UV-vis absorption spectroscopy, and electrochemical impedance spectroscopy, respectively. The results show that the RGO addition can enhance the photocatalytic performance of Bi2O3-RGO composites. Bi2O3-RGO composite with 2 wt.% RGO achieves maximum MO and MB degradation rates of 93% and 96% at 240min under visible light irradiation, respectively, much higher than those for the pure Bi2O3 (78% and 76%). The enhanced photocatalytic performance is ascribed to the increased light adsorption and the reduction in electron-hole pair recombination in Bi2O3 with the introduction of RGO.


Dopamine cross-reacts with adrenoreceptors in cortical astrocytes to induce BDNF expression, CREB signaling and morphological transformation.
Expression of brain-derived neurotrophic factor (BDNF) is induced in cultured rat cortical astrocytes by catecholamines norepinephrine and dopamine as well as selective α1 and β adrenergic agonists. However, it has remained unknown which receptors mediate dopamine-induced BDNF upregulation in astrocytes. Here, we demonstrate that β adrenoreceptors are the main mediators of this effect in cultured cortical astrocytes, while α1 adrenoreceptors and D1 dopamine receptors contribute to a lesser extent. We show that in cortical astrocytes BDNF exon IV and exon VI containing mRNAs are induced by dopamine and norepinephrine via CREB-dependent signaling and that this regulation is mediated by a mechanism that is distinct from activity-dependent CREB-mediated activation of BDNF transcription in neurons. We also show that regulation of BDNF promoters IV and VI by catecholamines requires a distal regulatory element in the BDNF locus. Finally, we demonstrate that dopamine-induced astrocyte stellation and induction of CREB signaling are mediated by cross-reaction of dopamine with β adrenoreceptors.


Growth characteristics and oxidative capacity of Acetobacter aceti IFO 3281: implications for L-ribulose production.
We studied the growth characteristics and oxidative capacities of Acetobacter aceti IFO 3281 in batch and chemostat cultures. In batch culture, glycerol was the best growth substrate and growth on ethanol occurred only after 6 days delay, although ethanol was rapidly oxidized to acetic acid. In continuous culture, both glycerol and ethanol were good growth substrates with similar characteristics. Resting cells in a bioreactor oxidized ribitol to L-ribulose with a maximal specific rate of 1.2 g g(-1) h(-1)). The oxidation of ribitol was inhibited by ethanol but not by glycerol. Biomass yield (Y(SX); C-mmol/C-mmol) on ethanol and glycerol was low (0.21 and 0.17, respectively). In the presence of ribitol the yield was somewhat higher (0.25) with ethanol but lower (0.13) with glycerol, with respectively lower and higher CO(2) production. In chemostat cultures the oxidation rate of ribitol was unaffected by ethanol or glycerol. Cell-free extract oxidized ethanol very slowly but not ribitol; the oxidative activity was located in the cell membrane fraction. Enzymatic activities of some key metabolic enzymes were determined from steady-state chemostat with ethanol, glycerol, or ethanol/glycerol mixture as a growth limiting substrate. Based on the measured enzyme activities, metabolic pathways are proposed for ethanol and glycerol metabolism.


Assessment of DNA damage in leukocytes from infected and malnourished children by single cell gel electrophoresis/comet assay.
The alkaline single cell gel (SCG) assay is a sensitive electrophoretic technique for detecting the presence of DNA single strand breaks and alkali-labile damage in individual cells. This technique was used to assess and compare the level of DNA damage in peripheral blood leukocytes/lymphocytes from well-nourished children with infection, well-nourished children with infection and under drug treatment, and from malnourished infected children with and without previous drug treatment. The present study shows that severe infection is associated with a significant increase in DNA damage. The average migration length was five times greater in severely infected well-nourished children compared to that found in healthy, well-nourished children. The results obtained in this study indicate that malnutrition is another factor associated with an increase in DNA migration. The average tail length for malnourished, severely infected children was twice as great as that obtained for cells from well-nourished, severely infected children. We also detected a variable increase in DNA migration associated with treatment for severe infection. Nevertheless, the excessive heterogeneity, the concurrent number of drugs used and the limited size of the treated population precludes an accurate assessment of which drugs were involved in the increase in DNA damage. Further studies will be necessary involving a large number of patients to address the relation between levels of DNA damage and specific kinds of infection, various drug treatments, and the type and severity of malnutrition. The increased level of DNA damage in severely infected and malnourished children could be related to negative effects such as a deficient immune response resulting in an increased susceptibility to malignant transformation.


Relation between umbilical cord blood pH, base deficit, lactate, 5-minute Apgar score and development of hypoxic ischemic encephalopathy.
Umbilical cord acid-base analysis is fundamental for assessing intrapartum hypoxia. The accuracy of arterial umbilical cord blood lactate, pH and base deficit to reflect a low 5-minute Apgar score and hypoxic ischemic encephalopathy (HIE) stage 2-3 was assessed, and new gestational age-adjusted reference standards were compared with traditional stationary reference values. A total of 13,735 pH-validated routine cord acid-base values from singleton deliveries were tested with stationary and gestational age-adjusted reference values using receiver operating characteristic curves and calculation of area under curve. University hospital. Accuracy of low pH, high base deficit and high lactate, alone or in combination, to imply 5-minute Apgar score < 7 or < 4 or HIE. Gestational age-adjusted values were for all parameters significantly better than crude values to indicate Apgar score < 7. For Apgar score < 4, the differences were not significant. The frequency of HIE was 0.046%, making statistical analyses pointless. Gestational age-adjusted lactate had the overall best accuracy and among combinations; a low age-adjusted pH plus high age-adjusted lactate was slightly better than a low age-adjusted pH plus high age-adjusted base deficit. The sensitivity and positive predictive value were low for all parameters. Lactate in cord arterial blood at birth is at least as good as base deficit to reflect an impaired condition at birth, and best when gestational age-adjusted values are used. Due to methodological confounding involved in calculation of base deficit, lactate may replace base deficit as an acid-base outcome parameter at birth.


Application of a tape recorder ZK-246 for four-channel recording of some physiological phenomena.
A method of simultaneous recording of our physiological phenomena on a magnetic tape was described. A block construction of a transducer enabling four-channel record on a two channel, stereophonic tape recorder has been presented.


Shared decision making on medication use between nurses and patients in an oncology setting: A qualitative descriptive study.
(i) To explore patients' and nurses' experiences with medication-related shared decision making (SDM) (i.e., familiarity with the concept, application of medication-related SDM, barriers and facilitators towards its application) and (ii) to explore their role perceptions, respectively. A qualitative study was conducted in which seven interviews with oncological patients and a focus group interview with six nurses were performed. Prior to the interviews, observations of the application of shared decision making were conducted using the OPTION-12 scale. The observations were used exclusively to trigger the group discussion. Data were collected from November 2020 until March 2021. According to participants, the application of SDM regarding medication by nurses in oncology is limited. Barriers mentioned were health status, medication-related knowledge, the therapeutic nurse-patient relationship, time pressures and workload. Patients valued nurses' contribution to SDM regarding medication and perceived them as key persons because of their advocating, informative, facilitating and supportive role. Individual and contextual factors determined patients' desire for involvement in medication-related decisions. Participants solely concentrated on SDM concerning drug choice and management of therapeutic and adverse effects. The patients' and nurses' experiences and perceptions towards SDM in other domains of pharmaceutical care need further investigation.


Pharmacologic Control of Blood Pressure in Infants and Children.
Alterations in blood pressure are common during the perioperative period in infants and children. Perioperative hypertension may be the result of renal failure, volume overload, or activation of the sympathetic nervous system. Concerns regarding end-organ effects or postoperative bleeding may mandate regulation of blood pressure. During the perioperative period, various pharmacologic agents have been used for blood pressure control including sodium nitroprusside, nitroglycerin, β-adrenergic antagonists, fenoldopam, and calcium channel antagonists. The following manuscript outlines the commonly used pharmacologic agents for perioperative BP including dosing regimens and adverse effect profiles. Previously published clinical trials are discussed and efficacy in the perioperative period reviewed.


Substrate specificity of thermostable farnesyl diphosphate synthase with alkyl group homologs of isopentenyl diphosphate.
3-Alkyl group homologs of isopentenyl diphosphate were examined for the reactivity as substrates of the thermostable farnesyl diphosphate (FPP) synthase of Bacillus stearothermophilus. Even 3-n-propyl- and 3-n-butyl-but-3-enyl diphosphates, which are hardly acceptable by animal FPP synthases, are accepted by this bacterial enzyme as substrates to react with dimethylallyl- and geranyl diphosphates, yielding 7-methyl-3-n-propylocta-2,6-dienyl- and 7,11-dimethyl-3-n-propyldodeca-2,6,10-trienyl diphosphate, respectively.


Rice organs concentrate cadmium by chelation of amino acids containing dicarboxyl groups and enhance risks to human and environmental health in Cd-contaminated areas.
When rice plants grown in paddy fields with Cd content of 0.3-1.5 mg kg-1, Cd quantities in roots and straws were 2-7 times higher than that in topsoil. Return of these vegetative organs to topsoil aggravated the ecological risk of Cd pollution. Cd content in rice grains was 0.1-1.3 mg kg-1, and hazard quotients for local consumers by intake of these rice were 0.7-8.8. Planting low-Cd-accumulating (LCA) cultivar reduced hazard quotients for consumers by intake of rice, but had similar ecological risks as high-accumulating (HCA) cultivars. LCA cultivar had lower Cd content in grains as well as higher efficiency of altering Cd into insoluble forms in flag leaves and upmost nodes than HCA cultivars. Insoluble Cd content in nodes was linearly increased with soil Cd content, companied by significant decline of 4 amino acids with dicarboxyl groups. Glu or Asp can form a cyclic complex with Cd by two O atoms from α-COO- and side chain-COO-. These results indicate that roots and straws have high potential to concentrate Cd by forming complexes between amino acids and Cd ions, and Cd-enriched straw return to topsoil may aggravate the ecological risk of Cd contamination.


Anti-TNF certolizumab pegol induces antioxidant response in human monocytes via reverse signaling.
Anti TNF drugs have been widely used in rheumatoid arthritis (RA) but only 70 to 80 % of patients respond to this therapy. Exploring the mode of action of anti-TNF drugs remains important in order to improve the efficiency of the treatment and enhance our knowledge of inflammation. TNF-α exists as classical soluble cytokine as well as transmembrane protein (tmTNF-α). Evidence suggests that tmTNF-α can induce reverse signaling. In the present study, we have explored consequences of reverse signaling in human monocytes using certolizumab pegol (CZP). Monocytes were purified from healthy blood donors and were incubated with CZP. Nuclear translocation of Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) was evaluated by wide-field microscopy and cell fractionation. Heme oxygenase 1 (HO-1) was assessed by RT-qPCR and western blot. Monocytes were stimulated with lipopolysaccharide (LPS). IL-1β was quantitated by RT-qPCR. Reactive oxygen species (ROS) were evaluated by flow cytometry using the H2DCFDA fluorescent marker. CZP induced rapid minimal ROS production and Nrf2 nuclear translocation. This was followed by HO-1 mRNA and protein production. IL-1β induction by LPS was inhibited at the mRNA and protein level. At a later time-point, CZP was able to counteract the strong production of ROS induced by LPS. Reverse signaling was suggested by short kinetics of Nrf2 translocation, extensive washing of CZP and the use of anti-TNF-Rs antibodies. Our data suggest a novel mechanism of ROS modulation by CZP. This observation sheds new light on the function of reverse signaling and on potential mechanisms of action of anti-TNF drugs.


Comparison of nasal prongs and nasopharyngeal catheter for the delivery of oxygen in children with hypoxemia because of a lower respiratory tract infection.
To determine the best method of oxygen delivery for children in developing countries who have hypoxemia caused by acute lower respiratory tract infection. One hundred eighteen children between 7 days and 5 years of age with a lower respiratory tract infection and arterial hemoglobin oxygen saturation (Sao2) less than 90% were randomly selected to receive oxygen by nasopharyngeal (NP) catheter (n = 56) or nasal prongs (n = 62). A crossover study to determine the flow rate necessary to achieve an Sao2 of 95% was performed in 60 children. One hundred twelve children could be oxygenated by the allocated method; in six oxygenation was poor with either method. The mean duration of therapy was 87.5 hours for the prongs and 94.9 hours for the NP catheter (not significant). The median oxygen consumption was 2142 L for prongs and 1692 L for the NP catheter (not significant). In the crossover study the prongs needed, on average, 26% higher oxygen flow rates than the NP catheter to obtain an Sao2 of 95% (p = 0.003). Complete nasal obstruction was observed in 24 of the children (44%) in the NP catheter group and in 8 (13%) in the prongs group (p < 0.001). Eighteen children died, 11 with NP catheter and 7 with prongs (not significant). Because nasal prongs are less prone to complications, and oxygenation in children is equally effective, they are a more appropriate method than the NP catheter for oxygen delivery to children in developing countries with acute lower respiratory tract infections.


A rare variation of the coeliac trunk.
The hepatic, splenic and Left gastric arteries are considered as the "main classic branches" of the coeliac trunk. During the routine dissections in the laboratory of the Anatomy Department in a 62-year-old male cadaver, a rare variation, a coeliacomesenteric trunk was observed. This trunk gave rise to the left gastric, the common hepatic, the splenic, the left gastro-epiploic, the right and left inferior phrenic arteries. The developmental and clinical significance of this anomalous vessel is discussed.


Cannabinoid-induced upregulation of serotonin 2A receptors in the hypothalamic paraventricular nucleus and anxiety-like behaviors in rats.
Recent behavioral reports suggest that repeated exposure to cannabis and synthetic cannabinoid agonists is linked with mental disorders associated with dysfunction of serotonin 2A (5-HT2A) receptor neurotransmission such as anxiety and depression. Here, we studied the effect of a nonselective cannabinoid agonist, CP55940, on the activity of 5-HT2A receptors in hypothalamic paraventricular nucleus (PVN). We detected that repeated exposure to CP55940 enhanced the prolactin and corticosterone neuroendocrine responses mediated by 5-HT2A receptors and increased the membrane-associated levels of 5-HT2A receptors in PVN. Importantly, we also detected increased anxiety-like behaviors in CP55940 treated rats compared to controls. The data presented here suggest that the mechanisms mediating the cannabinoid-induced upregulation of 5-HT2A receptors would be brain-region specific, as we were unable to detect a CP55940-induced upregulation of 5-HT2A mRNA. Our results might provide insight into the molecular mechanism by which repeated exposure to cannabinoids could be associated with the pathophysiology of neuropsychiatric disorders.


Subjective Visual Vertical Tilt Attraction to the Side of Rod Presentation: Effects of Age, Sex, and Vestibular Disorders.
The aim of this study was to evaluate the effect of initial rod position on the subjective visual vertical (SVV) tilt and to investigate the effect of sex and age on the SVV tilt induced by this initial position. Prospective cross-sectional study. Tertiary referral center. The study included 6598 consecutive patients with a large range of vestibular disorders and 333 control subjects. The mean age was 55 years (range, 3-97), and the sex ratio was 0.6. SVV was measured by presenting a phosphorescent rod 12 times in total darkness with a 45-degree deviation from the vertical alternatively on the right and left. The patient was asked to replace the bar vertically with a remote control. On average, SVV at each iteration was tilted to the side of the rod presentation. It was stronger in female subjects, in younger individuals (<20 years) and seniors (>50). It was also higher in patients with a left vestibular loss in comparison to those with a right involvement. These effects suggest that short-term visual memory and multisensory cortical processing interfere with SVV measurements.


Improving the inaccuracies of clinical staging of patients with NSCLC: a prospective trial.
Clinical stage affects the care of patients with nonsmall cell lung cancer. This is a prospective trial on patients with suspected resectable nonsmall cell lung cancer. All patients underwent integrated positron emission tomographic scanning and computed tomographic scanning, and all suspicious metastatic sites were investigated. A, T, N, and M status was assigned. If N2, N3 and M1 were negative, patients underwent thoracotomy and complete thoracic lymphadenectomy. There were 383 patients. The accuracy of clinical staging using positron emission tomographic scanning and computed tomographic scanning was 68% and 66% for stage I, 84% and 82% for stage II, 74% and 69% for stage III, and 93% and 92% for stage IV, respectively. N2 disease was discovered in 115 patients (30%) and was most common in the subcarinal lymph node (30%). Unsuspected N2 disease occurred in 28 patients (14%) and was most common in the posterior mediastinal lymph nodes (subcarinal, 38%; posterior aortopulmonary, 15%). It was found in 9% of patients who were clinically staged I (58% in the posterior mediastinal lymph nodes) and in 26% of patients clinically staged II (86% in posterior mediastinal lymph nodes). Despite integrated positron emission tomographic scanning and computed tomographic scanning, clinical staging remains relatively inaccurate for patients with nonsmall cell lung cancer. Recent studies suggest adjuvant therapy for stage Ib and II nonsmall cell lung cancer; thus the impact on preoperative care is to find unsuspected N2 disease. Unsuspected N2 disease is most common in posterior mediastinal lymph nodes inaccessible by mediastinoscopy. Thus one should consider endoscopic ultrasound fine-needle aspiration, especially for patients clinically staged as I and II, even if the nodes are negative on positron emission tomographic scanning and computed tomographic scanning.


Proteomic analysis of Plasmodium berghei in the ring phase during in vivo antiparasitic treatment with kramecyne.
Malaria is a parasitic disease of global importance due to its high annual death toll. The treatment for this infection is difficult for the increase in the populations of parasites resistant to the existing medicines, the development of new antimalarials is urgent needed. Several products developed for the control of malaria from herbalist have had a profound impact, for example, quinine obtained from the bark of the cinchona tree and recently those derived from artemisinin, whose discovery was the reason for the awarding of the 2015 Nobel Prize. The aim of the present study was to evaluate a compound named kramecyne extracted of "chayotillo" (Krameria cystisoides) plant used by the antiparasitic effect against some blood and intestinal protozoa (Giardia duodenalis y Trypanosoma cruzi). In addition is using for the treatment of inflammatory diseases. Measuring parasitaemia at different times, it was observed that in mice treated with kramecyne, it reached only 14% of parasitaemia at 7 days with a dose of 15 mg/kg, using chloroquine as a control drug, because it has not been demonstrated that parasites that infect rodents have developed resistance against this drug. Our results showed that kramecyne decreases the expression of parasite proteins that participate in biological processes, such as invasion, cytoadherence, pathogenicity and energy metabolism. With these results, it is proposed that this compound has repercussions on the metabolism of the parasite and could be useful for use as an antimalarial.


Flexor tendon rupture associated with an anomalous muscle.
A rupture occurred in the substance of an apparently normal flexor digitorum profundus tendon of a left small finger. It was associated with a previously undescribed anomalous flexor digitorum superficialis of the brevis type to the same finger. Clinical reports of 20 anomalous flexor digitorum superficialis muscles were found in the literature; all but one were on the right side or bilateral and occurred predominantly in females. Three cases were of the brevis type and all involved the index finger. Although the precise reason for rupture is not known we have speculated that the anomalous superficialis may have given rise to a deficient vinculum longus to the profundus predisposing it to failure.


New insights into NO adsorption on alkali metal and transition metal doped graphene nanoribbon surface: A DFT approach.
The aim of this article is to investigate the sensing performance of NO gas molecule on the graphene nanoribbon domain for the determination of structural and electronic properties. Effect of an alkali metal (lithium) and a transition metal (iron) on the armchair oriented graphene nanoribbon (ArGNR) surface for the sensing purpose of NO gas has been performed through the quantum mechanics based Density Functional Theory (DFT) calculations. Various configurations of ArGNR doped with Li and Fe atoms such as one-edge doped, center doped, both-edge doped Li-ArGNR and Fe-ArGNR have been simulated, and a detailed comparative study of lithium and iron doping on different configurations of ArGNRs for the adsorption energy, stability analysis, band gap analysis and density of states analysis has been quantitatively evaluated. By comparing the adsorption energy of NO, it is found that Li doping enhances the strength of NO adsorption on the different variants of ArGNR. Computational results predict that the undoped ArGNR is insensitive to the NO gas adsorption with adsorption energy of about -0.41 eV. Our results determine that substitutional doping of Li doping at one edge doped and both-edge doped position increases the adsorption abilities of ArGNRs in these configurations with adsorption energies of approximately -6.92 eV and -9.64 eV that is 16 and 23 times greater than the pristine ArGNR (Pr-ArGNR). Band nature for both type of doping estimates the changing behavior of ArGNRs from semiconductor to metallic transition after the adsorption of NO molecule. It is concluded that the Li doping at one edge and both edge position of ArGNR makes it an excellent potential sensing material for the sensing purpose of NO gas as compared to the Fe doped configurations.


Distinguishing Four Calliphoridae Species (Diptera) from Jamaica Using the Cephalopharyngeal Skeleton: Application to Forensic Investigations.
Flies of the family Calliphoridae, commonly called blow flies, are important in the decomposition process. Knowledge on their succession pattern on corpses, species identification and the duration of their life cycle stages can be useful in forensic investigations especially when estimating the post-mortem interval. We performed linear-based morphometrics on the cephalopharyngeal skeleton of four blow fly species found in Jamaica to distinguish species and determine larval development stage. We collected eggs from pigs' heads used as bait in the field and conducted rearing exercises in the laboratory. We used the internal skeletonized structure, the cephalopharyngeal skeleton, to develop a practical and efficient method for species identification. For the first instar, we found species can be differentiated using all the measurements analysed in the study. We found that the mouth hook length may be useful in distinguishing larvae in the second instar. For the larvae in the third instar, the whole length of the skeleton, from mouth hook to length of the dorsal cornue, may be useful for separating species. We provide information on the cephalopharyngeal skeleton of Lucilia lucigerens (James), a blow fly species endemic to Jamaica, for the first time. Our work provides relevant information that could be utilized for species identification and life stage determination if fly evidence is to be incorporated in forensic investigations in Jamaica.


Luteinizing hormone and follicle stimulating hormone secretion patterns in female athletes with and without menstrual disturbances.
Thirty-one young female athletes and 13 age-matched sedentary controls were studied throughout one menstrual cycle or over a 6 week period. Blood was sampled on 5 days per week. Episodic gonadotrophin secretion was measured in the early follicular phase and in the late luteal phase by blood sampling over a 12-h period at 15-min intervals. Eight athletes had anovulatory cycles, nine had impaired progesterone (P4) secretion during the luteal phase and 14 had normal cycles as judged from oestradiol (E2) and P4 plasma levels. Athletes with normal cycles had shorter cycles, lower E2 maxima at midcycle, and lower E2 and P4 concentrations during the luteal phase than had sedentary controls. Episodic luteinizing hormone (LH) secretion in the early follicular phase was significantly impaired in the anovulatory athletes: the average LH values over 12 h and the number of secretion episodes were significantly reduced. No significant changes were seen in follicle stimulating hormone secretion.


Correlation between Reynolds number and eccentricity effect in stenosed artery models.
Flow recirculation and shear strain are physiological processes within coronary arteries which are associated with pathogenic biological pathways. Distinct Quite apart from coronary stenosis severity, lesion eccentricity can cause flow recirculation and affect shear strain levels within human coronary arteries. The aim of this study is to analyse the effect of lesion eccentricity on the transient flow behaviour in a model of a coronary artery and also to investigate the correlation between Reynolds number (Re) and the eccentricity effect on flow behaviour. A transient particle image velocimetry (PIV) experiment was implemented in two silicone based models with 70% diameter stenosis, one with eccentric stenosis and one with concentric stenosis. At different times throughout the flow cycle, the eccentric model was always associated with a greater recirculation zone length, maximum shear strain rate and maximum axial velocity; however, the highest and lowest impacts of eccentricity were on the recirculation zone length and maximum shear strain rate, respectively. Analysis of the results revealed a negative correlation between the Reynolds number (Re) and the eccentricity effect on maximum axial velocity, maximum shear strain rate and recirculation zone length. As Re number increases the eccentricity effect on the flow behavior becomes negligible.


The stimulation of mitogenic signaling pathways by N-POMC peptides.
The N-terminal fragment of pro-opiomelancortin (POMC) has been shown previously to act as an adrenal mitogen. However, little is known about the molecular mechanisms by which mitogenesis is stimulated, although it has been shown that N-POMC(1-28) stimulates the ERK pathway in human H295R cells. We have investigated signaling stimulated by N-POMC(1-28) and N-POMC(1-49) in the mouse Y1 cell line and found that both peptides stimulate ERK phosphorylation with maximal stimulation being achieved within 5min. Similar results were observed for both MEK and c-Raf phosphorylation, although N-POMC(1-49) stimulated the phosphorylation of Akt more robustly than N-POMC(1-28). We also investigated the expression of tyrosine kinase receptors in adrenal cells. PCR utilizing degenerate primers was performed on cDNA from both Y1 cells and rat adrenal tissue. Sequencing of 114 clones from each cDNA population revealed the expression of a number of receptors, several of which have not been described previously in the adrenal.


Analyzing Illumina Gene Expression Microarray Data Obtained From Human Whole Blood Cell and Blood Monocyte Samples.
Microarray profiling of gene expression is widely applied to studies in molecular biology and functional genomics. Experimental and technical variations make not only the statistical analysis of single studies but also meta-analyses of different studies very challenging. Here, we describe the analytical steps required to substantially reduce the variations of gene expression data without affecting true effect sizes. A software pipeline has been established using gene expression data from a total of 3358 whole blood cell and blood monocyte samples, all from three German population-based cohorts, measured on the Illumina HumanHT-12 v3 BeadChip array. In summary, adjustment for a few selected technical factors greatly improved reliability of gene expression analyses. Such adjustments are particularly required for meta-analyses of different studies.


Bioorthogonal chemistry and illumination controlled programmed size-changeable nanomedicine for synergistic photodynamic and hypoxia-activated therapy.
Photodynamic therapy (PDT) can aggravate the hypoxia aggravation and be further utilized for the activation of hypoxia-activated prodrug (HAP). Ideally, photosensitizers (PSs) are mainly administrated to tumor vasculatures adjacent to regions with high oxygen to effectively generate reactive oxygen species (ROS) effectively and further aggravate tumor hypoxia, while the HAP is delivered to the inner tumor as far as possible for efficient activation. However, a delivery system capable of transporting PSs and HAP to the desired region respectively for the optimum effect is urgently needed. Here, we developed a bioorthogonal click chemistry and illumination controlled programmed size-changeable nanomedicine for synergistic photodynamic and hypoxia-activated therapy. It utilized tumor acidity responsive bioorthogonal click reaction for crosslinking nanoparticles to construct a drug depot with tumor vasculatures adjacent region retention for PDT in normoxia. Under laser illumination, cleavage of the ROS-responsive thioketal (TK) crosslinker to release small sized poly(amidoamine) (PAMAM) dendrimer conjugated with HAP for enhanced tumor penetration into the hypoxic region. Therefore, this strategy could differentially deliver PSs and HAP in desired spatial distribution, eventually achieving the enhanced synergistic enhancement in the combined PDT and hypoxia-activated therapy.


Predictors for a positive outcome of adapted clinical dry bed training in adolescents and adults with enuresis.
Adapted Dry Bed Training (Adapted DBT) has been shown to be effective in therapy-resistant adolescents and adults with enuresis. Given the substantial impact of enuresis and the time-consuming nature of Adapted DBT, we investigated which patients benefited most from Adapted DBT. Therefore, we identified predictors for a successful treatment response to Adapted DBT in this population. Retrospective cohort study in 907 consecutive patients, aged 11-42 years, subjected to in-hospital Adapted DBT in our Dry Bed Center between January 2003 and July 2013. Outcome was defined as treatment success after six months (primary outcome) and six weeks. Results of logistic regression analyses are presented in odds ratios and 95% confidence intervals. Predictors for a successful treatment response to Adapted DBT in adolescents and adults with enuresis after six months are: gender (female), initial degree of enuresis (mild: 0-3 nights/week), current diaper use, never used anticholinergics in the past, and degree of enuresis six weeks after training. Predictors for successful treatment response after six weeks are: gender and initial degree of enuresis only. The low explained variance of our model, showing that many other factors, not included in our study, could be of interest in the prediction of success. Several factors that predicted a successful treatment response of Adapted DBT after six weeks and six months were identified. However, the low explained variance of our model suggests that other non-identified factors are also important in predicting outcome. Neurourol. Urodynam. 35:1006-1010, 2016. © 2015 Wiley Periodicals, Inc.


Sexual dimorphism in fat distribution and metabolic profile in mice offspring from diet-induced obese mothers.
To investigate whether the effects of diet-induced obesity in mothers are passed on to their offspring fed a control diet in a gender-specific manner. Mother mice received either standard chow (SC; 17% energy from fat) or high-fat (HF; 49% energy from fat) diet for eight weeks pre-pregnancy until lactation. After weaning (at 21 days of age), offspring received SC diet and were divided into four groups according to the mother's diet (Mo): male Mo-SC, female Mo-SC, male Mo-HF, and female Mo-HF. Stereology, Elisa and western blotting were performed. HF diet-fed mothers were overweight, and had metabolic abnormalities, all of which were found in their adult offspring. Male Mo-HF offspring had higher cholesterol, triglycerides, leptin and insulin levels and lower circulating adiponectin than female Mo-HF offspring. Mo-HF offspring of both genders had higher expression of tumor necrosis factor-alpha, interleukin-6 and leptin and lower expression of adiponectin than Mo-SC offspring; however, male Mo-HF were more affected than female Mo-HF offspring for these variables, demonstrating sexual dimorphism. Exposure to HF diet is effective in inducing obesity and metabolic alterations in mothers, and this phenotype can be passed on to their offspring. An adverse pattern in the body fat distribution in males probably has favored the intensification of a pro-inflammatory profile compared with females. In adulthood, the male offspring responds to the maternal obesity more than the female offspring, indicating a relevant sexual dimorphism that is a novel finding in this animal study.


Brain stem afferents of hypoglossal neurons in the rat.
The origin of afferent connections of the hypoglossal nucleus in rats was investigated using horseradish peroxidase (HRP) as a retrograde tracer. Pressure injections (0.15-0.17 mu1) of 15% HRP were introduced into the rostral, middle and caudal portions of the nucleus. Projections to the hypoglossal nucleus originated from 3 regions of the brainstem: the reticular formation, the spinal V complex and the nucleus of the solitary tract. Bilateral projections with ipsilateral predominance came from the lateral reticular formation: the dorsal aspect of the nucleus reticularis parvocellularis and its caudal continuation, the nucleus reticularis dorsalis. Fewer projections emerged from two nuclei of the medial reticular formation. The dorsal part of the nucleus reticularis ventralis at the spinomedullary junction contributed bilateral with mainly contralateral input to hypoglossal neurons. A few labeled neurons were situated bilaterally in the nucleus reticularis gigantocellularis of the rostral medulla. The input from the spinal V complex originated from the dorsal aspect along most of its length but particularly from the pars interpolaris and oralis subdivisions. Labeled neurons were located primarily in the posterior portion of the nucleus of the solitary tract. Projections from the spinal V complex and the solitary nucleus exhibited ipsilateral predominance. These results suggest that somatic and visceral centers of the rat brainstem play an important role in the control of the activity of hypoglossal motoneurons.


A fast and reliable system for microcomputerized DNA cytofluorometry in tumour pathology.
A microcomputerized cytofluorometry system based on a Leitz MPV 3 cytophotometer, and intended for DNA measurements in tumour pathology is described. The system has been equipped with a reference channel for correction of excitation light instability. The importance of the adjustment of the epi-illumination for optimal performance of the reference channel is stressed, and a detailed description is provided. An apparatus variability well below 1% CV is obtained even during periods of marked instability of the arc-lamp. Software for conventional cytofluorometry with which about 200 cells can be measured in 20 min is presented. In addition a measuring technique where cells are not positioned, but are just passed through the excitation light spot is described. Preliminary results on cytocentrifuged specimens of human cancers indicate that this system is at least three times faster than conventional fluorometry. The increased speed of measurements considerably extends the possibilities to evaluate cell proliferation using static cytofluorometry. The measuring capacity of course is dependent upon the quality of the specimen. In well prepared cytocentrifuged specimens 1000 cells have been measured in 35 min.


Effects of dioctadecyl dimethyl ammonium chloride on the rheological behavior of behenyl trimethyl ammonium chloride/1-hexadecanol/water ternary system.
The effects of dioctadecyl dimethyl ammonium chloride (DODAC) on the rheological properties of ternary systems consisting of behenyl trimethyl ammonium chloride (C22TAC), 1-hexadecanol (C16OH), and water are studied to improve the long-term stability and to establish the preparation method of cosmetic products. The basic ternary systems behave as solids at low stresses, due to the formation of lamella liquid crystals called alpha gel. The additions of DODAC to ternary systems cause the rupture of alpha gel structures and transformation to vesicles. The structures of molecular assemblies are confirmed through particle size distribution, differential scanning calorimetry, and freeze fracture electron microscopy. The vesicle structures formed in coexistence of single-chain surfactant and double-chain surfactant are highly stable. Because the quaternary systems are considered to be constructed by the mixtures of alpha gel and vesicles at the appropriate concentrations of DODAC, the rheology can be controlled by the structural balance between them.


Calculating the uncertainty in lead concentration for in vivo bone lead x-ray fluorescence.
A revised mathematical treatment of the calibration line intercept has been published for in vivo bone lead measurements using 109Cd-based K-shell x-ray fluorescence. The revised calibration line treatment prompts changes, presented herein, to the method for calculating the measurement uncertainty.


Cost-effectiveness of ticagrelor plus aspirin versus aspirin in acute ischaemic stroke or transient ischaemic attack: an economic evaluation of the THALES trial.
THALES demonstrated that ticagrelor plus aspirin reduced the risk of stroke or death but increased bleeding versus aspirin during the 30 days following a mild-to-moderate acute non-cardioembolic ischaemic stroke (AIS) or high-risk transient ischaemic attack (TIA). There are no cost-effectiveness analyses supporting this combination in Europe. To address this, a cost-effectiveness analysis was performed. Cost-effectiveness was evaluated using a decision tree and Markov model with a short-term and long-term (30-year) horizon. Stroke, mortality, bleeding and EuroQol-5 Dimension (EQ-5D) data from THALES were used to estimate short-term outcomes. Model transitions were based on stroke severity (disabling stroke was defined as modified Rankin Scale >2). Healthcare resource utilisation and EQ-5D data beyond 30 days were based on SOCRATES, another trial in AIS/TIA that compared ticagrelor with aspirin. Long-term costs, survival and disutilities were based on published literature. Unit costs were derived from national databases and discounted at 3% annually from a Swedish healthcare perspective. One-month treatment with ticagrelor plus aspirin resulted in 12 fewer strokes, 4 additional major bleeds and cost savings of €95 000 per 1000 patients versus aspirin from a Swedish healthcare perspective. This translated into increased quality-adjusted life-years (0.04) and reduced societal costs (-€1358) per patient over a lifetime horizon. Key drivers of cost-effectiveness were number of patients experiencing subsequent disabling stroke and degree of disability. Findings were robust over a range of input assumptions. One month of treatment with ticagrelor plus aspirin is likely to improve outcomes and reduce costs versus aspirin in mild-to-moderate AIS or high-risk TIA. NCT03354429.


Identification of a nuclear carbonic anhydrase in Caenorhabditis elegans.
Carbonic anhydrases (CA) catalyze the inter-conversion of CO(2) with HCO(3) and H(+), and are involved in a wide variety of physiologic processes such as anion transport, pH regulation, and water balance. In mammals there are sixteen members of the classical α-type CA family, while the simple genetic model organism Caenorhabditis elegans codes for six αCA isoforms (cah-1 through cah-6). Fluorescent reporter constructs were used to analyze gene promoter usage, splice variation, and protein localization in transgenic worms. Catalytic activity of recombinant CA proteins was assessed using Hansson's histochemistry. CA's ability to regulate pH as a function of CO(2) and HCO(3) was measured using dynamic fluorescent imaging of genetically-targeted biosensors. Each of the six CA genes was found to be expressed in a distinct repertoire of cell types. Surprisingly, worms also expressed a catalytically-active CA splice variant, cah-4a, in which an alternative first exon targeted the protein to the nucleus. Cah-4a expression was restricted mainly to the nervous system, where it was found in nearly all neurons, and recombinant CAH-4A protein could regulate pH in the nucleus. In addition to establishing C. elegans as a platform for studying αCA function, this is the first example of a nuclear-targeted αCA in any organism to date. A classical αCA isoform is targeted exclusively to the nucleus where its activity may impact nuclear physiologic and pathophysiologic responses.


Identifying Clinically Significant Prostate Cancers using 3-D In Vivo Acoustic Radiation Force Impulse Imaging with Whole-Mount Histology Validation.
Overly aggressive prostate cancer (PCa) treatment adversely affects patients and places an unnecessary burden on our health care system. The inability to identify and grade clinically significant PCa lesions is a factor contributing to excessively aggressive PCa treatment, such as radical prostatectomy, instead of more focal, prostate-sparing procedures such as cryotherapy and high-dose radiation therapy. We have performed 3-D in vivo B-mode and acoustic radiation force impulse (ARFI) imaging using a mechanically rotated, side-fire endorectal imaging array to identify regions suspicious for PCa in 29 patients being treated with radical prostatectomies for biopsy-confirmed PCa. Whole-mount histopathology analyses were performed to identify regions of clinically significant/insignificant PCa lesions, atrophy and benign prostatic hyperplasia. Regions of suspicion for PCa were reader-identified in ARFI images based on boundary delineation, contrast, texture and location. These regions of suspicion were compared with histopathology identified lesions using a nearest-neighbor regional localization approach. Of all clinically significant lesions identified on histopathology, 71.4% were also identified using ARFI imaging, including 79.3% of posterior and 33.3% of anterior lesions. Among the ARFI-identified lesions, 79.3% corresponded to clinically significant PCa lesions, with these lesions having higher indices of suspicion than clinically insignificant PCa. ARFI imaging had greater sensitivity for posterior versus anterior lesions because of greater displacement signal-to-noise ratio and finer spatial sampling. Atrophy and benign prostatic hyperplasia can cause appreciable prostate anatomy distortion and heterogeneity that confounds ARFI PCa lesion identification; however, in general, ARFI regions of suspicion did not coincide with these benign pathologies.


Epidemiology, Screening, and Prevention of Bladder Cancer.
Bladder cancer (BC) represents a significant health problem due to the potential morbidity and mortality associated with disease burden, which has remained largely unaltered over time. To provide an expert collaborative review and describe the incidence, prevalence, and mortality of BC and to evaluate current evidence for BC screening and prevention. Data on the estimated incidence and mortality of BC for 2020 in 185 countries were derived from the International Agency for Research on Cancer GLOBOCAN database. A review of English-language articles published over the past 5 yr was conducted using PubMed/MEDLINE to identify risk factors in addition to contemporary evidence on BC screening and prevention. BC is the tenth most common cancer worldwide, with 573 278 cases in 2020. BC incidence is approximately fourfold higher in men than women. Tobacco smoking remains the principal risk factor, accounting for approximately 50% of cases. There is insufficient evidence to recommend routine BC screening. However, targeted screening of high-risk individuals (defined according to smoking history or occupational exposure) may reduce BC mortality and should be the focus of prospective randomized trials. In terms of disease prevention, smoking cessation represents the most important intervention, followed by a reduction in exposure to occupational and environmental carcinogens. BC confers a significant disease burden. An understanding of BC epidemiology and risk factors provides an optimal foundation for disease prevention and the care of affected patients. Bladder cancer is the tenth most common cancer worldwide and is approximately four times more common among men than among women. The main risk factors are tobacco smoking, followed by exposure to carcinogens in the workplace or the environment. Routine screening is not currently recommended, but may be beneficial in individuals at high risk, such as heavy smokers. Primary prevention is extremely important, and smoking cessation represents the most important action for reducing bladder cancer cases and deaths.


Multimorbidity and simultaneity of health risk factors, from adolescence to early adulthood: 1993 Pelotas Birth Cohort.
The co-occurrence of two or more diseases is called multimorbidity, and the occurrence of two or more risk factors is called simultaneity of risk factors. Multimorbidity and simultaneity of risk factors are not widely understood in adolescence and early adulthood. This paper aims to describe how multimorbidity and simultaneity of risk factors are distributed throughout adolescence and early adulthood, considering demographic and socioeconomic characteristics, among the 1993 Pelotas Birth Cohort members. This study was carried out using data from the 11, 15, 18, and 22y of the 1993 Pelotas Birth Cohort, Brazil (n = 5249). A self-reported questionnaire assessed allergies, asthma/bronchitis/wheezing, diabetes, vision problems, hypertension, common mental disorders, other mental disorders, physical inactivity, sedentary behaviour, insufficient sleep time, smoking, alcohol abuse behaviour, and illicit drugs. Glucose, cholesterol, blood pressure, weight, and height were objectively collected. The prevalence of multimorbidity was 26.3%, 31.3%, 37.9%, and 44.4% at 11, 15, 18, and 22y, respectively. Around 70% of all ages presented simultaneity of risk factors. Women presented a higher prevalence of simultaneity of risk factors, and the multimorbidity gradually increased from 11 to 22y. The presence of both multimorbidity and simultaneity of risk factors was 19.7% at 11 and 35.4% at 22y. Less than 2% have no morbidity and no risk factors at each age assessed. This study highlighted the early emergence and accelerated growth of diseases and risk factors in a young population, especially their co-occurrence.


Cloning a cuticle-degrading serine protease gene with biologic control function from Beauveria brongniartii and its expression in Escherichia coli.
Beauveria brongniartii extracellular subtilisin-like serine protease (Pr1) is one of the most virulent factors by virtue of its activity against insect cuticles. The Pr1 cDNA was cloned using the switching mechanism at the 5' end of the RNA transcript and rapid amplification of cDNA ends. The 1732-bp fragment of genomic DNA containing the predicted open-reading frame of the Pr1 gene was cloned by polymerase chain reaction and sequenced. The Pr1 cDNA is 1550 bp and contains an 1140-bp ORF. The deduced amino-acid sequence of the protein shows identity to that of proteinase K from Tritirachium album (62%), Pr1 from Metarhizium nisopliae (67%), and Pr1 from B. bassiana (76%). The Pr1 protein with an N-terminal fusion to the six-histidine tag was expressed in Escherichia coli as inclusion bodies with the expression vector pBV220. Sodium dodecylsulsulfate-polyacrylamide gel electrophoresis clearly revealed expressed product. The Pr1 protein was purified and refolded and had proteolytic activity of 0.288 U mg(-1).


Nonfamilial Multiple Trichoepithelioma: Few and Far Between.
Trichoepithelioma is a rare benign adnexal tumor which may be of solitary nonfamilial type or multiple familial trichoepitheliomas. Here, we describe a rare presentation of nonfamilial case of trichoepithelioma in a 50-year-old female with multiple skin colored facial papules and nodules over the face, upper back, and extremities.


Immobilization of mammalian eggs on solid substrates by lectins for electron microscopy.
Cumulus-free, zona pellucida invested hamster and mouse eggs were immobilized by adherence of the zonae to glass or plastic substrates to which the lectin, wheatgerm agglutinin, had been attached. This simple method of egg immobilization enabled processing of very small quantities of eggs for both scanning and transmission electron microscopy. Soluble protein in the medium did not affect zona-substrate adhesion, and virtually all of the eggs were retained during dehydration and critical point drying.


Food supply and prey selection in planktivorous cyprinidae.
In small Bavarian lakes, the gut contents of the Cyprinid fish roach (Rutilus rutilus), rudd (Scardinius erythrophtalamus), bream (Abramis brama) and bleak (Alburnus alburnus), and the actural food supply during the fish's feeding period were examined in relation to the species composition of zooplankton. Accompanied by feeding experiments in the laboratory, the selective effect of fish predation could be attributed to the distribution patterns of prey and predator in time and space, to the prey's specific visibility and escape ability and, to some extent, to the fish's active choice. The possibility that the species composition of zooplankton is regulated was indicated only in the fish's positively abundance-dependent preference for the prey types and restricted to only a few plankter species.


Complications of suture ligation ablation for ulnar polydactyly: a report of two cases.
We report two cases resulting in complications following suture ligation treatment for ulnar polydactyly. One case consisted of bilateral, retained gangrene and cellulitis, and a second case consisted of a residual, sensitive skin tag. The case involving gangrene and cellulitis developed after an unsuccessful suture ligation of bilateral pedunculated duplicated digits. The second case developed after suture ligature ablation of a rudimentary digit in the nursery but presented 3 years later with a residual symptomatic nubbin. Both cases were treated by surgical excision of the residual tissue in the operating room. The first case illustrates a morbid complication following unsuccessful ligature while the second case demonstrates the inevitable suboptimal long-term outcome associated with what has traditionally been considered "successful" suture ligation.


Pterostilbene, a dimethylated analog of resveratrol, promotes energy metabolism in obese rats.
Pterostilbene (trans-3,5-dimethoxy-4-hydroxystilbene) is a dimethylated analog of resveratrol and has been reported to exert various pharmacological effects. In this study, we evaluated the effect of pterostilbene on the pathogenesis of obesity and energy metabolism in obese rats. Pterostilbene significantly activates silent mating type information regulation 2 homolog-1 and peroxisome proliferator-activated receptor-alpha in vitro. At 4 weeks a 0.5% pterostilbene diet markedly suppressed the abdominal white adipose tissue (WAT) accumulation in obese rats. The oxygen consumption and energy expenditure were significantly higher in the pterostilbene group, and pterostilbene increased the fat metabolism rather than the carbohydrate metabolism in obese rats. The mRNA level of uncoupling protein, a thermogenic regulator, was increased and the mRNA levels of fatty acid synthase and leptin, which are involved in lipogenesis and fat storage, were markedly decreased in WAT after the pterostilbene feeding. These results suggest that pterostilbene prevents WAT accumulation through the enhancement of energy metabolism and partly the suppression of lipogenesis in obese OLETF rats.


Daptomycin use in neutropenic patients with documented gram-positive infections.
The goal of this study was to describe the outcomes associated with daptomycin treatment of documented gram-positive infections in patients with neutropenia. All patients with neutropenia (≤500 cells/m(3)) and at least one documented gram-positive culture from 2006-2009 were identified from a retrospective, multicenter, and observational registry (Cubicin(®) Outcome Registry and Experience (CORE(®))). Investigators assessed patient outcome (cured, improved, failed, nonevaluable) at the end of daptomycin therapy. All patients were included in the safety analysis. The efficacy population had 186 patients; 159 (85 %) patients had either cure (n = 108, 58 %) or improved (n = 51, 27 %) as an outcome. Success rates (cure plus improved) by the lowest WBC during daptomycin were 98/116 (84 %) for ≤100 cells/m(3) and 61/70 (87 %) for 101-499 cells/m(3), P = 0.6. Most patients had cancer; 135/186 (73 %) had hematological malignancy; 26/186 (14 %) had solid tumors, and 9 (5 %) had both. One hundred fifty-six (84 %) patients received other antibiotics before daptomycin treatment; 82 % vancomycin, of which 31 % failed vancomycin. The most common infections were bacteremia (78 %), skin and skin structure infections (8 %), and urinary tract infections/pyelonephritis (6 %). The most common pathogens were vancomycin-resistant Enterococcus faecium (47 %), methicillin-resistant Staphylococcus aureus (20 %), and coagulase-negative staphylococci (19 %). The median (min, max) initial daptomycin dose was 6 mg/kg (3.6, 8.3). The median (min, max) daptomycin duration of therapy was 14 days (1, 86). Possibly related adverse events occurred in 12/209 patients (6 %), and 13 patients (6 %) discontinued daptomycin due to adverse event. The results suggest that daptomycin appeared useful and well tolerated in neutropenic patients, and the degree of neutropenia did not affect daptomycin success rates. Comparative clinical trials are needed to confirm these findings.


Calcium deficiency, pregnancy, and lactation in rats. Microscopic and microradiographic observations on bones.
Adult female rats were subjected to a calcium-depriving regimen (calcium-deficient diet containing oxalate + pregnancy + lactation) to obtain maximum bone mineral mobilization in as short a time as possible. The femur and tibia were investigated by histological, microradiographic and fluorescent microscopic methods. The regimen caused osteoporosis, which varied in severity with the degree of calcium deprivation. Most of the bone tissue removed was taken from the metaphyseal trabeculae and from the endosteal surface of the diaphysis. The remaining bone tissue seemed unchanged. The cells responsible for the bone removal did not seem to be multinucleated osteoclasts, but mononuclear, hypertrophied, elongated cells, possibly derived from the "resting" osteoblasts normally lining the bony surfaces. No signs of osteocytic osteolysis were observed. Bone formation was reduced, but present even in the most calcium-deprived animals. No increase in the amount of osteoid was observed.


Diagnosis of a carotid body chemodectoma with dynamic radionuclide perfusion scanning.
The first case of a carotid body chemodectoma that was diagnosed using dynamic radionuclide perfusion angiography and subsequently excised is presented. The value of this technic in the investigation of pulsatile tumors is emphasized.