Solar-mediated degradation of linezolid and tedizolid under simulated environmental conditions: Kinetics, transformation and toxicity.
Linezolid (LIN) and Tedizolid (TED) are representatives of oxazolidinone antibiotics of last resort with a strong efficacy against gram-positive bacteria. This study focused on their solar-mediated degradation to understand better their fate in aquatic environment, for the realistic concentrations in the range of 1 μg/L. Results showed that both antibiotics (ABs) are degradable by simulated sunlight (1 kW/m2), with half-lives of 32 and 93 h in ultrapure water, for LIN and TED, respectively. LIN showed similar photolytic behaviour in pure solution and in surface water, whereas sunlight enhanced the degradation of LIN in pure solutions, but not in surface water. Structure elucidation by liquid chromatography coupled to high resolution mass spectrometry provided information about seven transformation products for LIN and five for TED. The morpholinyl-ring was identified as the target site for most transformation reactions of LIN. TED was prone to oxidation and cleavage of the oxazolidinone ring. Results of a growth inhibition test on Bacillus subtilis exposed to UV light showed antibacterial efficacy of transformation products of LIN and no significant efficacy of degradation products of TED for the concentration range of 100 μg/L-10 mg/L of parent compounds. Photolytically treated solutions of the ABs maintained their inhibitory effect on the bioluminescence of Aliivibrio fischeri.


Scheduling radiotherapy for patients with nasopharyngeal carcinoma in the corresponding time window can reduce radiation-induced oral mucositis: A randomized, prospective study.
To explore a new method to reduce radiation-induced oral mucositis by scheduling radiotherapy for patients with nasopharyngeal carcinoma (NPC) in the corresponding time window of the cycle of oral mucosal cells. Eighty-two NPC patients were randomly divided into a day group (n = 41) and a night group (n = 41). The radiotherapy was scheduled at noon (11:30-15:30) for the day group, while at night (19:00-23:00) for the night group. Oral mucositis and oral pain were recorded in both groups after each radiotherapy fraction. The short-term efficacy of primary tumor regression, weight loss, and bone marrow suppression was recorded. The incidence of Grade 2 oral mucositis was 87.8% (36/41) and 63.4% (26/41) in the night group and day group, respectively (p = 0.010). The incidence of Grade 3 oral mucositis was 65.9% (27/41) and 22.0% (9/41) in the night group and day group, respectively (p < 0.001). The mean number of radiotherapy for patients to develop Grade 2 oral mucositis was 15.67 ± 5.05 and 20.92 ± 6.21 in the night group and day group, respectively. The incidence of Grade 2 oral pain was 48.8% (20/41) and 22.0% (9/41) in the night group and day group, respectively (p = 0.011). There were no significant differences in tumor regression, weight loss, and bone marrow suppression between the two groups. By scheduling radiotherapy based on the corresponding time window of the cycle of oral mucosal cells, the severity of oral mucositis in NPC patients was reduced.


Influence of ambient temperature on plasma ammonia and lactate accumulation during prolonged submaximal and self-paced running.
This study examined the effects of heat stress on the accumulation of plasma ammonia, lactate, and urate during prolonged running. Nine highly trained endurance runners completed two running trials in a counterbalanced fashion in cool (15 degrees C) and in hot (35 degrees C) humid (60% relative humidity) conditions. Subjects ran on a motorised treadmill at 70% of peak treadmill running speed for 30 min (submaximal) followed by a self-paced 8-km performance run. Blood was drawn at pre-exercise, end-submaximal and end-performance run and analysed for plasma ammonia, lactate, and urate. Four subjects failed to complete the performance run in the heat and the performance times for the rest of the subjects was increased from 27.3 (0.6) min in cool conditions to 31.3 (1.2) min in hot conditions (P < 0.05). The end-performance rectal temperature was 38.6 (0.1) and 39.2 (0.1) degrees C (P<0.05) in cool and hot conditions, respectively. Differences in plasma lactate at the end of submaximal running were not significant. However, at the end of performance runs lactate was 6.0 (0.9) m mol x l(-1) in cool and 3.1 (0.5) mmol x l(-1) in hot conditions, values that were significantly different (P<0.05). Plasma ammonia increased from pre-exercise to approximately equal to 59 micromol x l(-1) at the end-submaximal runs for both coditions and further at the end of performance runs to 108.5 (11) micromol x l(-1) (P<0.05) in hot but not in cool conditions. Plasma urate increased from pre-exercise to 311.2 (25.9) micromol x l(-1) at end-submaximal runs and to approximately equal to 320.4 micromol x l(-1) at end-performance runs in hot and cool environments. The findings that plasma urate accumulation was similar at the completion of running in both conditions, while ammonia was significantly augmented in hot conditions compared with cool, suggest that ammonia accumulation during heat stress exercise might be derived from sources other than purine catabolism.


Decreased expression of CD200 and CD200 receptor in Alzheimer's disease: a potential mechanism leading to chronic inflammation.
Inflammatory activation of microglia in response to neurodegenerative changes in diseases such as Alzheimer's disease (AD) and Parkinson's disease has been extensively described. These observations have suggested that inflammation could be contributing to disease progression. In this paper, the potential role of CD200 and CD200 receptor (CD200R), whose known functions are to activate anti-inflammatory pathways and induce immune tolerance through binding of CD200 to CD200 receptor (CD200R), was studied in AD. Quantitative studies showed a significant decrease in CD200 protein and mRNA in AD hippocampus and inferior temporal gyrus, but not cerebellum. Immunohistochemistry of brain tissue sections of hippocampus, superior frontal gyrus, inferior temporal gyrus and cerebellum from AD and non-demented cases demonstrated a predominant, though heterogeneous, neuronal localization for CD200. Decreased neuronal expression was apparent in brain regions affected by AD pathology. There was also a significant decrease in CD200R mRNA expression in AD hippocampus and inferior temporal gyrus, but not cerebellum. Low expression of CD200R by microglia was confirmed at the mRNA and protein level using cultured human microglia compared to blood-derived macrophages. Treatment of microglia and macrophages with interleukin-4 and interleukin-13 significantly increased expression of CD200R. Expression of these cytokines was not generally detectable in brain. These data indicate that the anti-inflammatory CD200/CD200R system may be deficient in AD brains. Mechanisms aimed at increasing levels of CD200 and CD200R could have therapeutic potential for controlling inflammation in human neurodegenerative diseases.


Design and synthesis of hybrids of diarylpyrimidines and diketo acids as HIV-1 inhibitors.
Based on the strategy of molecular hybridization, diketo acid fragment as a classical phamacophore of integrase inhibitors was introduced to reverse transcriptase inhibitors diarylpyrimidines to design a series of diarylpyrimidine-diketo acid hybrids (DAPY-DKAs). The target molecules 10b and 11b showed inhibitory activities against WT HIV-1 with EC50 values of 0.18μM and 0.14μM, respectively. And the results of molecular docking demonstrated the potential binding mode and revealed that the DKA moiety and its ester could both be tolerated in the nonnucleoside binding site (NNBS) of HIV-1 RT.


Factors Associated With Condom Failure in a Longitudinal Cohort of Men Who Have Sex With Men and Transgender Women in Abuja and Lagos, Nigeria.
Effective condom use is a critical intervention to limit the spread of HIV and other sexually transmitted infections, particularly among individuals in high-risk networks who practice anal sex. We characterized condom failures in cisgender men who have sex with men and transgender women in Nigeria. The TRUST/RV368 cohort provided condoms, compatible lubricants, and safer sex education to men who have sex with men and transgender women at community-engaged health centers in Abuja and Lagos, Nigeria. Participants completed structured interview questions about condom usage and failure every 3-6 months. Robust Poisson regression models with generalized estimating equations were used to estimate relative risks and 95% confidence intervals for prespecified factors potentially associated with condom failure in the previous month. From September 2013 to September 2019, 2221 of 2737 participants (81.1%) reported condom use for anal sex with a male partner in the last month, and 305 (13.7%) reported condom failure during this time. Multivariate analyses demonstrated an increased risk of condom failure at postenrollment visits, as well as in participants who reported frequent Internet use, 2 or more casual sexual partners, and 2-4 main sexual partners. Those who cohabited with a woman had reduced risk. Condom failure was common in this population despite freely available condoms, compatible lubrication, and education. Increased risk of condom failure over time could reflect message fatigue a ceiling for effective condom use, or new uptake of condoms by inexperienced users.


Muscle transposition in the management of chronic osteomyelitis and ulceration of the heel.
Transposition of intrinsic muscles of the foot may be beneficial for coverage of local full-thickness defects. A case representing this situation is presented. The authors report successful resolution of the procedure 28 months postoperatively.


Estimation of stabilities of staphylococcal nuclease mutants (Met32-->Ala and Met32-->Leu) using molecular dynamics/free energy perturbation.
We performed molecular dynamics (MD)/free energy perturbation (FEP) calculations to reproduce the experimental free energy difference of denaturation for staphylococcal nuclease mutant Met32-->Ala (M32A) and to predict the stability of the mutant Met32-->Leu (M32L). The calculated free energy difference of denaturation for the M32A of -1.9 kcal/mol was in good agreement with the experimental value. In the M32A, a small hydrophobic core formed by three aromatic rings (Tyr-27, Phe-34, Phe-76) in a wild-type crumbled as a result of exposure to water. The van der Waals interactions in the native state of the M32A were weaker than those of the wild-type, which strongly suggests that the Met-32 is important for the stability of the enzyme. The M32L has not been available yet, but is expected to retain the small hydrophobic core. The free energy difference of denaturation for the M32L was calculated to be 1.6 kcal/mol. The MD/FEP simulation showed that the native state structure of the M32L was only slightly changed when compared with that of the wild-type. It was suggested that the M32L is more stable than the wild-type because the electrostatic interactions in the denatured state are more disadvantageous than those in the native state.


Effects of selective estrogen receptor agonists on food intake and body weight gain in rats.
Ovariectomized (OVX) rats eat more and gain weight more rapidly than sham-operated (SO) rats and estradiol (E(2)) treatment attenuates food intake and body weight gain in OVX rats. Studies were designed to test the hypothesis that the alpha subtype of the estrogen receptor (ERalpha) mediates the attenuating effects of E(2) on food intake and body weight gain while the beta subtype (ERbeta) mediates opposing actions that lead to increased food intake and body weight gain. Female rats were SO or OVX and treated daily with vehicle (dimethylsulfoxide, DMSO) or E(2) (10 microg/day), or the ERalpha-selective agonist, 4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT, 0.5 mg/day), or the ERbeta-selective agonist, 2,3-bis(4-hyroxyphenyl)-propionitrile (DPN, 0.5 mg/day) for 14 days. Total food intake was significantly reduced by E(2) and PPT, but not DPN. Total body weight gain was significantly increased in OVX rats compared to SO rats and treatment with E(2) or PPT, but not DPN, significantly decreased total body weight gain to levels that were not significantly different from SO rats. A dose-response study of PPT indicated that at 0.25 mg/day, PPT significantly reduced total 21-day food intake and body weight gain and, at 0.13 and 0.06 mg/day, PPT significantly reduced total body weight gain compared to OVX rats without significantly reducing total food intake. A dose-response study of DPN indicated that none of the three doses of DPN significantly altered total 21-day food intake or total body weight gain. These results suggest ERalpha mediates the attenuating effects of estrogens on food intake and body weight gain while ERbeta has no effect on these variables.


Accounting for motion in resting-state fMRI: What part of the spectrum are we characterizing in autism spectrum disorder?
The exclusion of high-motion participants can reduce the impact of motion in functional Magnetic Resonance Imaging (fMRI) data. However, the exclusion of high-motion participants may change the distribution of clinically relevant variables in the study sample, and the resulting sample may not be representative of the population. Our goals are two-fold: 1) to document the biases introduced by common motion exclusion practices in functional connectivity research and 2) to introduce a framework to address these biases by treating excluded scans as a missing data problem. We use a study of autism spectrum disorder in children without an intellectual disability to illustrate the problem and the potential solution. We aggregated data from 545 children (8-13 years old) who participated in resting-state fMRI studies at Kennedy Krieger Institute (173 autistic and 372 typically developing) between 2007 and 2020. We found that autistic children were more likely to be excluded than typically developing children, with 28.5% and 16.1% of autistic and typically developing children excluded, respectively, using a lenient criterion and 81.0% and 60.1% with a stricter criterion. The resulting sample of autistic children with usable data tended to be older, have milder social deficits, better motor control, and higher intellectual ability than the original sample. These measures were also related to functional connectivity strength among children with usable data. This suggests that the generalizability of previous studies reporting naïve analyses (i.e., based only on participants with usable data) may be limited by the selection of older children with less severe clinical profiles because these children are better able to remain still during an rs-fMRI scan. We adapt doubly robust targeted minimum loss based estimation with an ensemble of machine learning algorithms to address these data losses and the resulting biases. The proposed approach selects more edges that differ in functional connectivity between autistic and typically developing children than the naïve approach, supporting this as a promising solution to improve the study of heterogeneous populations in which motion is common.


Surgery of vagal paragangliomas: six patients and review of literature.
Vagal paragangliomas (VPs) represent a rare pathology in which surgery is usually recommended, but where experience is crucial to reduce the number of post-operative complications. In this study, we present our experience and a review of the literature. Between 1991 and 2006 we have treated 42 patients with 50 paragangliomas of the head and neck (26 carotid, 18 jugular/tympanic and 6 vagal). Examination of the literature (Medline and non-indexed Spanish source) from the last 30 years has revealed 23 series that each reported more than three cases; reaching a total of 332 VPs. VPs are infrequent among paragangliomas of the head and neck (6/50) presenting clinical peculiarities such as multiple tumours, and malignant evolution. Within this current series, surgery was possible in all cases. Post-operative dysfunction in cranial nerves was frequent (the cranial X nerve was systematically sacrificed). There were no bronco-aspirations or mortalities. The literature review reveals similar results. To obtain the best results, it is important that the candidates for surgery be selected by experts within multidisciplinary groups.


Actions of Cannabis sativa L. fixed oil and nano-emulsion on venom-induced inflammation of Bothrops moojeni snake in rats.
Bothrops moojeni snake venom (VBm) has toxins that cause pronounced tissue damage and exacerbated inflammatory reaction. Cannabis sativa L. is a plant species that produces an oil (CSO) rich in unsaturated fatty acids. Nano-emulsions have several advantages, such as better stability and higher penetrating power in membranes. Therefore, this study evaluated the effect of a nano-emulsion based on this herbal derivative (NCS) against VBm-induced inflammation in Wistar rats. The CSO and NCS were submitted to physicochemical characterization. The inflammatory process was induced by the VBm (0.10 mg/kg) as follows: rat paw edema, peritonitis, analysis of leukocyte infiltrate in gastrocnemius muscle of rats and formation of granulomatous tissue. No significant changes were observed when the NCS was submitted to the centrifugation and thermal stress tests. There was no phase separation, changes in density (0.978 ± 0.01 g/cm3) and viscosity (0.889 ± 0.15). The droplet diameter ranged from 119.7 ± 065 to 129.3 ± 0.15 nm and the polydispersity index ranged from 0.22 ± 0.008 to 0.23 ± 0.011. The results showed that treatments with CSO (200 and 400 mg/kg) and NCS (100 mg/kg) were able to decrease significantly (p < 0.001) the formation of edema and granulomatous tissue. The CSO and NCS groups significantly attenuated (p < 0.001) the recruitment of inflammatory cells in the tests for peritonitis and leukocyte infiltrate. The histopathological analysis of the gastrocnemius muscle showed a reduction in tissue damage caused by VBm. The results obtained in this study showed anti-inflammatory activity of the CSO which may be due to a high UFA content. The nanosizing, as evidenced by the incorporation of the CSO in the NCS improved the effect and opens the perspective for the obtainment of a nanomedicine in which a kinetic stable phytotherapic can be used at low doses.


Transcriptome of the coral Mussismilia braziliensis symbiont Sargassococcus simulans.
A transcriptomic profile of Sargassococcus simulans 103B3, isolated from the coral Mussismilia braziliensis in Abrolhos, Brazil, is presented. A total of 631.3 Mbp transcriptomic sequences were obtained. The transcriptomic analysis disclosed transcripts coding for enzymes relevant for holobiont health including genes involved in I. Light harvesting complex (LHC), II. Organic matter utilization and III. Oxidative stress and microbial defense (Oxidoreductases) enzymes. The isolate exhibited transcripts for uptake and utilization of a variety of carbon sources, such as sugars, oligopeptides, and amino acids by ATP-binding cassette (ABC) and tripartite ATP-independent periplasmic (TRAP) type transporters. Collectively, these enzymes indicate a mixotrophic metabolism in S. simulans with metabolic capabilities for the degradation of an array of organic carbon compounds in the coral Mussismilia and light harvesting within the low-light environments of Abrolhos.


Clinical Research into Treating Unexplained Recurrent Spontaneous Abortion during Early Pregnancy with the Qing Yi Tiao Mian Formula.
The present study aims to analyze the clinical effect of the Qing Yi Tiao Mian (QYTM) formula on unexplained recurrent spontaneous abortion (URSA) during early pregnancy and the immune balance of T lymphocytes. With their consent, 45 patients with URSA in weeks 4-9 of pregnancy were separated into three groups, i.e., the conventional fetal protection (n = 15), prednisone treatment (n = 10), and QYTM formula treatment (n = 20) groups. These patients received treatment once they had been diagnosed with an intrauterine pregnancy. The conventional fetal protection group was given progesterone (20 ∼ 40 mg daily injection) for four weeks. The prednisone treatment group was given progesterone (20 ∼ 40 mg daily injection) + prednisone (5 mg/d) for four weeks. The QYTM formula treatment group was given progesterone (20 ∼ 40 mg daily injection) + QYTM formula (one dose per day) for four weeks. In addition, women who had previously had a normal pregnancy were enrolled as a control group (n = 18). The success rate of the pregnancy in the first trimester was observed in each group, and the proportion of T lymphocytes in the peripheral blood before and after treatment was recorded. Among the 20 patients with URSA in the QYTM formula treatment group, 19 remained pregnant. Thus, the success rate during early pregnancy was 95%, which was significantly higher than the conventional fetal protection (53.33%) and prednisone treatment (70%) groups. The CD8+ T and natural killer (NK) cells population in the URSA groups was higher compared with the control group (P < 0.01). The QYTM formula treatment significantly decreased the ratio of CD8+ T lymphocytes (P < 0.01) and NK cells (P < 0.01). The QYTM formula significantly decreased the spontaneous abortion rate in patients with URSA during early pregnancy. The mechanism may be closely related to the inhibition of the killer lymphocytes' proliferation by CD8+ T lymphocytes and NK cells.


Living with diabetes: relationship to gender, duration and complications. A survey in northern Sweden.
A questionnaire was sent to 561 insulin-treated diabetic patients aged 20-50 years living in the province of Västerbotten in Northern Sweden to assess their experience of living with diabetes. The response rate was 87% (n = 488). Differences in the experience of living with diabetes related to gender, age, duration of diabetes, and chronic diabetic complications were reported. Men seemed to underestimate problems related to diabetes more than women. They worried less about long-term complications and hypoglycaemia, but were more troubled by the limitation of personal freedom caused by their diabetes. In spite of their worries, women more often than men found positive aspects in having diabetes. Younger patients also had a more positive attitude towards their disease, even though they more often thought that diabetes had negatively affected their relationships with friends. Patients with a shorter diabetes duration were more concerned about the management of their diabetes than were patients with a long duration. The fear of chronic complications increased with diabetes duration. Chronic complications most affected patients' views of diabetes, their self-perception, and social life. Patients with childhood onset of diabetes knew less about the implications of the disease, and this reduced the intensity of their psychological response to the diagnosis. In conclusion, social and medical factors affected how diabetic patients perceived their disease. These findings suggest that the outcome of diabetes health care might improve if it was more individually adapted to each patient's personal experience of the disease and the psychological needs related to it.


Operation or indomethacin for the premature ductus.
Indomethacin constricts the patent ductus arteriosus in approximately 70% of premature infants, but temporarily inhibits synthesis of all prostaglandins. Early toxicity of indomethacin is not prohibitive, but the possibility of late neurological deficits is raised by results of laboratory experiments. As yet, no late toxic effects of indomethacin have been observed. However, this possibility and the low morbidity (less than 2%) and mortality (less than 2%) of surgical ligation of the patent ductus arteriosus in premature infants favor operation except in carefully controlled and limited clinical trials.


The psychophsiology of aggressive drivers: comparison to non-aggressive drivers and pre- to post-treatment change following a cognitive-behavioural treatment.
Twenty drivers were remanded to our treatment program by the courts following arrests related to serious aggressive driving behaviors. Ten additional drivers entered our program in response to our advertisements thus identifying themselves as aggressive drivers. Psychophysiological assessments were conducted on all 30 drivers and heart rate (HR), systolic and diastolic blood pressure (SBP and DBP), and skin resistance level (SRL) were measured in response to exposure to a mental arithmetic neutral stressor, two idiosyncratic, audio-taped, aggressive driving vignettes (audio 1 and audio 2), and one non-driving related fearful vignette. Fourteen non-aggressive driving controls also completed the assessment. The results indicated that the aggressive drivers (ADs) showed significantly more SBP responsivity during audio 1 and audio 2 and significantly less SBP reactivity during the mental arithmetic stressor than the controls. The aggressive drivers then completed a four-week, group intervention which included relaxation techniques specifically targeting aggressive driving behaviors. The same psychophysiological assessment was conducted at post-treatment. The results showed significant pre- to post-treatment decreases in HR, p<0.003, SBP, p<0.01, and DBP, p<0.02 during audio 1. Similarly, decreases were evident in audio 2 in SBP, p<0.03 only. No decreases in reactivity occurred during the neutral stressor or fearful situation.


Study on prenatal diagnosis and pregnancy outcome analysis of fetuses with cardiac rhabdomyoma.
To investigate the prenatal imaging characteristics, genetic characteristics and pregnancy outcome of fetuses with cardiac rhabdomyoma. The prenatal ultrasound, cranial MRI imaging information and genetic test results of 35 fetuses prenatally diagnosed with cardiac rhabdomyoma were collected and retrospectively analyzed, and the pregnancy outcome was followed up. Cardiac rhabdomyomas mainly occurred in left ventricular wall and ventricular septum; cranial MRI imaging was found abnormal in 38.1% (8/21) of the fetuses; genetic test was found abnormal in 58.82% (10/17) of the fetuses; the fetus was born in 12 cases and the pregnancy was terminated in 23 cases. TRIO whole exome sequencing (TrioWES) is recommended as the genetic test regime for cardiac rhabdomyoma. The comprehensive evaluation of prognosis of fetuses needs to consider the genetic results and whether the brain is involved; the prognosis of fetuses with simple cardiac rhabdomyoma is good.


Isolation, screening, and optimization of the fermentation conditions of highly cellulolytic bacteria from the hindgut of Holotrichia parallela larvae (Coleoptera: Scarabaeidae).
From the hindgut contents of Holotrichia parallela, 93 cellulolytic bacterial isolates were isolated after enrichment in carboxymethyl cellulose medium. Among these isolates, a novel bacterium, designated HP207, with the highest endoglucanase productivity was selected for further study. This bacterium was identified as Pseudomonas sp. based on the results of the 16S ribosomal DNA analysis, morphological characteristics, and biochemical properties. The production of the endoglucanase was optimized by varying various physical culture conditions using a submerged fermentation method. Under the optimized fermentation conditions, the maximum endoglucanase activity of 1.432 U mL(-1) in bacterial cultures was obtained, higher than those of the most widely studied bacteria and fungi, which are the attractive candidates for the commercial producer of cellulase. And the crude endoglucanase enzyme was also highly thermostable; approximately 55% of the original activity was maintained after pretreatment at 70 °C for 1 h. Thus, from the present study, the bacterium can be added up to the database of cellulolytic bacteria.


Comparison of the inhibition capability of oleanolic acid and betulinic acid towards drug-metabolizing enzymes.
Human UDP-glucuronosyltransferases (UGTs) are important membrane proteins located in endoplasmic reticulum, and play important roles in metabolism of a variety of endogenous and exogenous compounds. To determine the influence of subtle difference in the structure of oleanolic acid and betulinic acid towards the inhibition towards the activity of UGT isoforms. In vitro glucuronidation of 4-methylumbelliferone (4-MU) reaction was employed as the probe reaction to determine the inhibition of these two compounds towards UGTs' activity. The inhibition of capability of oleanolic acid towards UGT1A6 and UGT1A8 were higher than betulinic acid. However, no significant difference was observed for the inhibition of oleanolic acid and betulinic acid towards UGT1A7. Furthermore, concentration-dependent behaviour was determined for the inhibition of oleanolic acid and betulinic acid towards UGT1A6 and UGT1A8. At various concentrations of oleanolic acid and betulinic acid, the inhibition of oleanolic acid towards UGT1A6 and UGT1A8 was higher than betulinic acid. Given that UGT1A6 and UGT1A8 play key role in the the inhibition of oleanolic acid towards UGT1A6 and UGT1A8 will induce drug-drug interaction and the risk of diseases.


Properties of the bubble protein, a defensin and an abundant component of a fungal exudate.
Colonies of the ascomycete fungus Penicillium brevicompactum Dierckx produce bright yellow-green fluorescent exudate bubbles on its surface when grown on standard plant cell culture medium. According to SDS-PAGE analysis, the exudate is enriched in one protein, named bubble protein (BP). Detailed characteristics of BP are described, and also its corresponding genomic promoter and terminator sequences that flank sequences encoding signal peptide and a precursor sequence upstream of that of the mature protein. Following on previous work, the protein is now biochemically characterized. BP, the structure of which mainly consists of beta sheets, has four very stable disulfide bridges that resist standard procedures for reduction. With such traits, BP can now be categorized as a new member of the ever growing class of defensins. Indeed, the protein revealed anti-fungal effects as it inhibits growth of the yeast Saccharomyces cerevisiae in a dose-dependent manner. Structural classification places BP into the group of proteins with a knottin fold, founding the BP superfamily. Based on genomic alignments that revealed very high homology to four proteins of related fungi, a 3D structure prediction of the corresponding proteins was made. In addition, it was discovered that the closely related fungus Penicillium chrysogenum encodes a BP homolog - in addition to its PAF protein, which also is similar to BP - further suggesting that fungi may possess more than one defensin.


A trans-acting regulatory product necessary for expression of the Drosophila melanogaster 68C glue gene cluster.
The mutation l(1)npr-1 is located at cytological location 2B5 on the X chromosome in Drosophila melanogaster. We have found that this mutation causes absence of the normal product of the 2B5 locus and that it has the following phenotypes: the 68C glue puff on the third chromosome does not regress when mutant salivary glands are cultured in the presence of ecdysterone; the three 68C glue protein mRNAs are not synthesized; and a transformed Drosophila strain carrying both a normal resident 68C Sgs-3 gene and an introduced functional Sgs-3 gene with only a few kb of flanking sequences expresses neither Sgs-3 RNA if the l(1)npr-1 mutation is crossed into the stock. Thus the normal product of the l(1)npr-1 gene is required for regression of the 68C puff, and the l(1)npr-1 gene product allows expression of the Sgs-3 gene by interacting, either directly or indirectly, with DNA sequences near this glue protein gene.


Oral rifampicin interferes with urine dipstick tests for patients with pulmonary tuberculosis.
Rifampicin (RMP) and its major metabolite, desacetyl rifampicin (dRMP), can interfere with urine dipstick tests (UDTs) in patients with tuberculosis (TB) who receive oral RMP. This study sought to examine the effects of RMP and dRMP on UDTs using 2 different urine dipsticks (i.e., Arkray's Aution Sticks 10EA and GIMA's Combi-Screen 11SYS Plus sticks). Urine colorimetry was applied to measure RMP concentrations and determine the range of total RMP concentration in the urine within 2-6 and 12-24 h of oral administration of RMP. In vitro interference assays and confirmatory tests were performed to evaluate the effects of RMP and dRMP on the analytes. The total RMP concentration in the urine of the 40 TB patients analyzed as urine sample was 88-376 µg/mL within 2-6 h and 22-112 µg/mL within 12-24 h of oral administration of RMP. Interference was observed for different analytes at consistent or varied RMP concentrations between the in vitro interference assays and the confirmatory tests, including 75 patients [Aution Sticks 10EA: 250, 250 µg/mL for protein (PRO); 400, 300 µg/mL for leukocyte esterase (LEU); Combi-Screen 11SYS Plus: 125, 150 µg/mL for ketones (KET); 500, 350 µg/mL for nitrite (NIT); 200, 300 µg/mL for PRO; 125, 150 µg/mL for LEU]. RMP and dRMP interfered with the analytes of the UDTs using the 2 urine dipsticks in different levels. The in vitro interference assay is not an ideal substitute for the confirmatory test. The collection of urine samples within 12-24 h of administration of RMP can prevent the interference caused by RMP and dRMP.


[Immunological adjuvants. Determinant factors in the efficacy-toxicity ratio of the contemporary vaccines].
To achieve effective and safe vaccines for the prevention of not yet controlled or re-emergent infectious diseases, one of the more importance aspects is to have immunological adjuvants that allow inducing a protective immune response with an appropriate safety profile. Since 1926 the aluminium compounds have been used as adjuvants for human vaccines, and only in the last 10 years have some new products been registered. Although there an enormous quantity of proposed candidates, the toxicity is the main factor that has limited their introduction into the clinic. In this work the mechanism of action are updated, and the toxicity of the immunological adjuvants are revised, especially those that have obtained clinical approval or are close to getting it.


Primary non-Hodgkin's lymphoma of the stomach: changing aspects and therapeutic choices.
Eighty-five consecutive patients, seen between 1970 and 1987, with primary gastric non-Hodgkin's lymphoma were studied to evaluate diagnostic findings and treatment results. At endoscopy three main patterns were recognized: ulceration (n = 21), diffuse infiltration (n = 16) and a polypoid mass (n = 26). Recently, the new technique of endoscopic ultrasonography was used to measure depth of infiltration and regional lymph nodes. Preoperative diagnosis altered the indication of surgery. Since 1978 surgical staging was performed in only 29% of the patients compared to 90% in the earlier period. In the later period stage II was more systematically treated with a combination of chemotherapy and radiotherapy. Over the whole period patients in stage I (n = 52) had a 5 year disease-free survival of 63%. In stage II 38% had a 5 year disease-free survival. Complications were one perforation and one haemorrhage after radiotherapy and two cases of haemorrhage after radiotherapy combined with chemotherapy. Intraabdominal recurrences were found in two cases. Recognition of endoscopic features may lead to early detection and ultimately improved survival.


Prostaglandin E2 produced by late induced COX-2 stimulates hippocampal neuron loss after seizure in the CA3 region.
Injection of kainic acid (KA) into the brain causes severe seizures with hippocampal neuron loss. KA has been shown to immediately induce cyclooxygenase-2 (COX-2) expression in hippocampal neurons, indicating that neuronal COX-2 might be involved in neuronal death. In this study, however, we reveal that the delayed COX-2 induction in non-neuronal cells after KA injection plays an important role in hippocampal neuron loss rather than early COX-2 expression in neurons. We find that KA microinjection into the hemilateral hippocampus shows a later induction of COX-2 expression in non-neuronal cells, such as endothelial cells and astrocytes. In the KA-injected side, PGE2 concentration gradually increases and peaks at 24 h after injection, when non-neuronal COX-2 expression also peaks. When this delayed PGE2 elevation is prevented by selective COX-2 inhibitor NS398, it can block hippocampal cell death. Moreover, COX-2 knockout mice are also resistant to neuronal death after KA treatment. These findings indicate that delayed PGE2 production by non-neuronal COX-2 may facilitate neuronal death after seizure. Inhibition of COX-2 to an extent similar to PGE2 elevation after onset of seizure may be useful to prevent neuronal death.


Osteitis pubis following laparoscopic Burch colposuspension: A case report.
Osteitis pubis is a condition which predominantly affects young athletes. However, it may also occur following uro-gynecological interventions. We report a case of osteitis pubis following laparoscopic Burch colposuspension. There are several theories on the pathogenesis of postoperative osteitis pubis and a wide variety of treatment options have shown inconsistent outcomes. In our case, the condition was diagnosed radiologically and was managed with antibiotics and analgesics, which resulted in complete recovery.


Patient- and Family-Centered Care as an approach to reducing disparities in asthma outcomes in urban African American children: A review of the literature.
We thank Cathy Eames (Director, Library Services, Detroit Medical Center) for valuable input and assistance with the search strategy. Funding for this research was supported by a grant from Children's Hospital of Michigan Research Foundation (Principal Investigator: Terrance L. Albrecht, Ph.D.). Patient- and family-centered care (PFCC) has the potential to address disparities in access and quality of healthcare for African American pediatric asthma patients by accommodating and responding to the individual needs of patients and families. To identify and evaluate research on the impact of family-provider interventions that reflect elements of PFCC on reducing disparities in the provision, access, quality, and use of healthcare services for African American pediatric asthma patients. Electronic searches were conducted using PubMed, CINAHL, and Psyclnfo databases. Inclusion criteria were peer-reviewed, English-language articles on family-provider interventions that (a) reflected one or more elements of PFCC and (b) addressed healthcare disparities in urban African American pediatric asthma patients (≤18years). Thirteen interventions or programs were identified and reviewed. Designs included randomized clinical trials, controlled clinical trials, pre- and post-interventions, and program evaluations. Few interventions were identified as explicitly providing PFCC in a pediatric asthma context, possibly because of a lack of consensus on what constitutes PFCC in practice. Some studies have demonstrated that PFCC improves satisfaction and communication during clinical interactions. More empirical research is needed to understand whether PFCC interventions reduce care disparities and improve the provision, access, and quality of asthma healthcare for urban African American children. PubMed, CINAHL, and Psyclnfo AA-African American: CCT-Controlled clinical trial; ED-Emergency Department; ETS-Environmental tobacco smoke; FCC- Family Centered Care; PFCC-Patient and Family Centered Care; RCT- Randomized, controlled trial.


Respiratory syncytial virus infection in elderly adults.
Respiratory syncytial virus (RSV) infection is now recognised as a significant problem in elderly adults. Epidemiological evidence indicates the impact of RSV in older adults may be similar to non-pandemic influenza, both in the community and in long-term care facilities. Attack rates in nursing homes are approximately 5-10% per year with significant rates of pneumonia (10-20%) and death (2-5%). Estimates using US health care databases and viral surveillance results over a 9-year period indicate that RSV infection causes approximately 10,000 all-cause deaths annually among persons >64 years of age. In contrast, influenza A accounted for approximately 37,000 yearly deaths in the same age group. The clinical features of RSV infection may be difficult to distinguish from those of influenza but include nasal congestion, cough, wheezing and low-grade fever. Older persons with underlying heart and lung disease and immunocompromised patients are at highest risk for RSV infection-related pneumonia and death. Diagnosis of RSV infection in adults is difficult because viral culture and antigen detection are insensitive, presumably because of low viral titres. The combination of serology and reverse transcriptase polymerase chain reaction assay offers the best sensitivity and specificity for the diagnosis of RSV but unfortunately these techniques are not widely available; consequently, most adult RSV disease goes unrecognised. Although treatment of RSV infection in the elderly is largely supportive, early therapy with ribavirin and intravenous gamma-globulin improves survival in immunocompromised persons. An effective RSV vaccine has not yet been developed. Therefore, prevention of RSV is limited to standard infection control practices, such as hand washing and the use of gowns and gloves.


Care provision for poststroke visual impairment.
We sought to explore the care provision for poststroke visual impairment and variations in this in the United Kingdom. Survey questions were developed and piloted with clinicians, academics, and users. Questions addressed types of visual problems; how these were identified, treated, and followed up; care pathways in use; links with other professions; and referral options. The survey was accessed via a Weblink, which was circulated through UK professional organizations to multiprofessional members of ophthalmic and stroke teams. A total of 548 completed electronic surveys were obtained. In all, 49.5% of respondents represented stroke teams, 42.5% eye teams, and 8% from other teams, for example, emergency care. Many respondents (41%) saw patients within 1 week of stroke. Nineteen percent did not personally test vision: 11% had a visiting clinician to test vision, and 22% used screening tools. Validated tests were used for the assessment of visual acuity (39.5%), visual field (57.5%), eye movement (48.5%), and visual function (58.5%). Visual problems suspected by family or professionals were high (88.5%). Typical overall follow-up period of vision care was less than 3 months. In all, 46% of respondents used designated care pathways for stroke survivors with visual problems; 33.5% of respondents did not provide visual information leaflets. Significant inequality exists in care for stroke survivors who experience visual problems. There is great variability in how vision screening is undertaken, which vision tests are used, methods of referral to eye care services, how visual problems are managed, and what vision information is provided to stroke survivors/carers. Further work is required to ensure equality and effective care.


Latency as a region contrast: Measuring ERP latency differences with Dynamic Time Warping.
Methods for measuring onset latency contrasts are evaluated against a new method utilizing the dynamic time warping (DTW) algorithm. This new method allows latency to be measured across a region instead of single point. We use computer simulations to compare the methods' power and Type I error rates under different scenarios. We perform per-participant analysis for different signal-to-noise ratios and two sizes of window (broad vs. narrow). In addition, the methods are tested in combination with single-participant and jackknife average waveforms for different effect sizes, at the group level. DTW performs better than the other methods, being less sensitive to noise as well as to placement and width of the window selected.


Prefrontal activation related to spontaneous creativity with rock music improvisation: A functional near-infrared spectroscopy study.
Understanding how the brain modulates improvisation has been the focus of numerous studies in recent years. Models have suggested regulation of activity between default mode and executive control networks play a role in improvisational execution. Several studies comparing formulaic to improvised sequences support this framework and document increases in activity in medial frontal lobe with decreased activity in the dorsolateral prefrontal cortex (DLPFC). These patterns can be influenced through training and neural responses may differ between in beginner and expert musicians. Our goal was to test the generalizability of this framework and determine similarity in neural activity in the prefrontal cortex during improvisation. Twenty guitarists performed improvised and formulaic sequences in a blues rock format while brain activity was recorded using functional near-infrared spectroscopy. Results indicate similar modulation in DLPFC as seen previously. Specific decreases of activity from left DLPFC in the end compared to beginning or middle of improvised sequences were also found. Despite the range of skills of participants, we also found significant correlation between subjective feelings of improvisational performance and modulation in left DLPFC. Processing of subjective feelings regardless of skill may contribute to neural modulation and may be a factor in understanding neural activity during improvisation.


Infraclavicular block causes less discomfort than axillary block in ambulatory patients.
This randomized study was designed to compare discomfort caused by axillary or infraclavicular blocks in ambulatory patients. We identified which of the three block components, needle passes, local anesthetic (LA) injections, and electrical stimulations, is most painful and quantified pain intensity on a visual analog scale (VAS 0-100). We also assessed onset and quality of analgesia, adverse events and patients' acceptance. Eighty patients were studied. In axillary group-A, four LA injections were made after stimulating median, musculocutaneous, ulnar and radial nerves. In infraclavicular group-I, the whole LA volume was injected after stimulating median or ulnar or radial nerves. Patients were ready for surgery when they had analgesia/anesthesia distal to the elbow. Median intensity of block discomfort was 22 in A group and 10 in I group (P < 0.01). There was no difference in distribution of the most painful block components between the groups. Block performance times were 4 min in I group and 7 min in A group (P < 0.01). Block onset times were 18 min in A group and 20 min in I group (NS). There was one block failure in I group. Three patients in A group and five in I group required supplementary blocks (NS). Transient adverse events occurred in 14 A-group and two I-group patients (P<0.01). Thirty-seven I-group and 33 A-group patients were satisfied with the block (NS). Infraclavicular block by single injection caused less discomfort and fewer adverse events than axillary block by multiple injections. Block effectiveness, onset time and patients' acceptance were similar.


Evidence of a strong interaction of 2,4-dichlorophenoxyacetic acid herbicide with human serum albumin.
The interaction of 2,4-dichlorophenoxyacetic acid herbicide (2,4-D) with human serum albumin (HSA) was studied using fluorescence and differential scanning calorimetry (DSC). Fluorescence displacement of 1-anilino-8-naphtalenesulfonate (ANS) bound to HSA was used to evaluate the binding affinity of 2,4-D to HSA. The binding is associated to a high affinity site of HSA located in the IIIA subdomain. The association constant (Kass) of the herbicide was about 5 microM(-1), several times higher than the affinity found for pharmaceutical compounds. This relatively strong interaction with HSA was evidenced by the increase in HSA protein thermostability induced as consequence of herbicide interaction. 2,4-D induces an increase in the midpoint of thermal denaturation temperature from 60.1 degrees C in herbicide free solution to 75.6 degrees C in full ligand saturating condition. The calorimetric enthalpy and the excess heat capacity also increased upon 2,4-D binding. To investigate the possibility of other/s system/s of 2,4-D transport in blood, besides of HSA, the interaction of the herbicide with lipid monolayers was explored. No interaction was detected with any of the lipids tested. The overall results provided evidence that high affinity 2,4-D-HSA complex exhibits enhanced thermal stability and that HSA is the unique transport system for 2,4-D in blood.


Maternal serum split and hairy-related protein 1 in preeclampsia versus normal pregnancy.
The primary objective was to compare maternal serum split and hairy related protein-1 (SHARP1) in preeclamptic women versus normal pregnant women. The secondary objectives were to compare maternal and neonatal outcomes between preeclampsia and normal pregnant women. This cross-sectional analytic study included 75 preeclamptic pregnant women and 75 normal pregnant women at Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital between March 2018 and May 2019. Blood was collected into nonheparinized tubes. Blood samples were centrifuged and stored at -80 °C until assayed. Maternal serum SHARP1 levels were measured by enzyme-linked immunosorbent assays. Maternal and neonatal outcomes were recorded. Median serum SHARP1 level in preeclampsia was significantly higher than in normal pregnancy (5.2 vs. 3.7 ng/mL, p = .007). Preeclamptic women had a higher rate of cesarean section than normal pregnant women (68% vs. 32%, p < .001). Preeclamptic women had lower neonatal birth weight than normal pregnant women (2,546.1 ± 766.3 vs 2,884.5 ± 479.9, p = .001). Neonatal complications were higher in preeclamptic women than normal pregnant women (40% vs. 17.3%, p = .002). Serum SHARP1 in preeclampsia was significantly higher than in normal pregnancy.


E-cadherin expression in the tumor microenvironment of advanced epidermal growth factor receptor-mutant lung adenocarcinoma and the association with prognosis.
The expression of programmed death-ligand 1 (PD-L1), tumor-infiltrating lymphocytes (TILs), E-cadherin, and vimentin in lung cancer tumor microenvironment is known to impact patient survival or response to therapy. The expression of these biomarkers may also differ between primary lung tumors and brain metastatic tumors. In this study, we investigated the interaction between these biomarkers in lung tumors with or without concomitant brain metastasis and the interaction with paired brain metastatic tumors. The study included 48 patients with stage IV epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma. Sixteen of the forty-eight patients were diagnosed with brain metastasis, while the remaining thirty-two were not. All sixteen patients with brain metastasis had brain tumors. The expression of PD-L1, TILs (CD8+ T lymphocytes and FOXP3+ regulatory T lymphocytes), E-cadherin, and vimentin were evaluated using immunohistochemical (IHC) staining. Patients with brain metastasis exhibited a higher frequency of exon 19 deletion and uncommon EGFR mutations, a higher lung tumor vimentin score, worse progression-free survival (PFS), and overall survival (OS) than patients without brain metastasis. IHC staining showed no difference between paired lung and brain tumors. Patients with low PD-L1 expression had better PFS and OS. After multivariate analysis, higher body mass index, the presence of brain metastasis, bone metastasis, and uncommon EGFR mutations were correlated with worse PFS, while the presence of brain metastasis and high lung tumor E-cadherin score was associated with worse OS. In patients with stage IV EGFR-mutant lung adenocarcinoma, high E-cadherin expression in the lung tumor might be associated with worse OS. Vimentin expression in the lung tumor was positively related to the risk of brain metastasis.


Evaluation of Cyantraniliprole and Other Commercial Fly Baits under Laboratory and Field Conditions.
Laboratory and field trials were performed to evaluate the attractiveness and efficacy of commercial baits (cyantraniliprole; methomyl + (Z)-9-tricosene; dinotefuran + (Z)-9-tricosene; imidacloprid granular + (Z)-9-tricosene; and imidacloprid liquid + (Z)-9-tricosene). In choice tests; flies were most attracted to cyantraniliprole bait > dinotefuran + (Z)-9 > methomyl + (Z)-9 bait > imidacloprid granular + (Z)-9 bait > imidacloprid liquid + (Z)-9 bait. Significant degradation in bait efficacy was observed after two weeks of aging excluding imidacloprid granular; which began to degrade in field conditions after one week. Cyantraniliprole; the new fly bait active ingredient in Zyrox(®); had the longest time to knockdown in the laboratory tests; but on susceptible flies; achieved 95%-100% knockdown within an hour of exposure. Zyrox(®) was resistant to weathering for a week; and was more attractive to flies in the field when compared to methomyl + (Z)-9 bait.


Smart textiles for multimodal wearable sensing using highly stretchable multiplexed optical fiber system.
This paper presents the development and application of a multiparameter, quasi-distributed smart textile based on embedded highly stretchable polymer optical fiber (POF) sensors. The POF is fabricated using the light polymerization spinning process, resulting a highly stretchable optical fiber, so-called LPS-POF, with Young's modulus and elastic limits of 15 MPa and 17%, respectively. The differential scanning calorimetry shows a thermal stability of the LPS-POF in temperature range of 13-40 °C. The developed sensors are based on the optical power variation, which results in a fully portable and low-cost technique. In order to obtain a multiplexed sensor system, a technique based on flexible light emitting diodes (LEDs) on-off keying modulation is applied, where each LED represents the response of one sensor. The smart textile comprises of LPS-POF and three flexible LEDs embedded in neoprene textile fabric. The performance of the system is evaluated for temperature, transverse force and angular displacement detection at different planes. The sensors presented high linearity (mean determination coefficient of 0.99) and high repeatability (inter-measurement deviations below 5%). The sensor is also applied in activity detection, where the principal component analysis (PCA) was applied in the sensors responses and, in conjunction with clustering techniques such as k-means, indicate the possibility of detecting basic activities such as walking, sitting on a chair and squatting.


The DnaJ-like zinc finger domain protein ORANGE localizes to the nucleus in etiolated cotyledons of Arabidopsis thaliana.
Vitamin A deficiency (VAD) is a worldwide health problem. Overexpression of the DnaJ-like zinc finger domain protein ORANGE (OR) is a novel strategy for the biofortification of pro-vitamin A carotenoids in different staple crops to alleviate VAD. In plants, OR triggers the differentiation from non-pigmented plastids into carotenoid-accumulating plastids. There are different reports on the subcellular localization of this protein in either chloroplasts or the nucleus, both of which were supported by confocal observation and protein-protein interaction results. In this work, we studied the subcellular localization of OR in the cotyledons of germinating seedlings whose plastids were transitioning from non-pigmented proplastids into carotenoid-accumulating etioplasts in the dark, and then into chloroplasts upon illumination. Our Western blot analysis identified two bands of the Arabidopsis OR protein (AtOR) from the chloroplast fraction of the mature leaves (i.e., a 34-kDa form corresponding to the full-length peptide and a 30-kDa form suggesting the removal of the N-terminal chloroplast transit peptide). We found that the full-length AtOR was predominantly localized in the nucleus in etiolated cotyledons, although its abundance decreased upon illumination. Our bioinformatics analysis indicated a nuclear localization signal (NLS) after the N-terminal chloroplast transit peptide. When we substituted different N-terminal regions of AtOR with the green fluorescent protein, our confocal observations demonstrated that this NLS was sufficient to target AtOR to the nucleus. Our results demonstrate that AtOR is a dual-targeted protein that mainly localizes in the nucleus in etiolated cotyledons.


Doramectin, a new avermectin highly efficacious against gastrointestinal nematodes and lungworms of cattle and pigs: two studies carried out under field conditions in Germany.
Two field studies were carried out to confirm the efficacy of doramectin in cattle and pigs in Europe. A total of 40 cattle harbouring naturally acquired infections of gastrointestinal nematodes, including Ostertagia spp., Oesophagostomum spp., Cooperia spp., Haemonchus spp., Nematodirus spp. and Trichuris spp., were allocated to a treated or a control group (20 animals/group), and 100 harbouring naturally acquired infections of gastrointestinal nematodes and lungworms, including Oesophagostomum spp., Metastrongylus spp., Ascaris suum and Trichuris suis, were allocated to either a treated (60 pigs) or a control (40 pigs) group. Animals in the treated groups received an injection of doramectin at 200 micrograms/kg (1 ml/50 kg) for cattle or 300 micrograms/kg (1 ml/33 kg) for swine. Animals in the control groups received saline at 1 ml/50 kg for cattle or 1 ml/33 kg for swine. The cattle were injected by the subcutaneous route in the lateral mid-line of the neck and the pigs were injected intramuscularly in the neck. Faecal egg counts were determined for all animals on days--7, 0, 7, 14 and 21 of the studies, where day 0 was the day of treatment. The mean daily weight gain of doramectin-treated animals was significantly higher than that of the control animals over the 21 days of the studies (P < 0.0007 for cattle and P = 0.0001 for swine). At 21 days after treatment, the mean faecal egg counts of the doramectin-treated animals were significantly lower than those of the control animals and were reduced by 100% as compared with pretreatment levels. No adverse reaction to treatment was observed in any animal during either study.(ABSTRACT TRUNCATED AT 250 WORDS)


Efficacy of tocilizumab for psychiatric symptoms associated with relapsing polychondritis: the first case report and review of the literature.
Relapsing polychondritis (RP) rarely affected the central nervous system (CNS). If the CNS is involved, it can result in psychiatric manifestations. Patients with RP always respond well to glucocorticoids and immunosuppressants. If the therapies fail, biologics can be given, such as tocilizumab, which is a humanized monoclonal antibody against the interleukin-6 receptor (IL-6R). Until now, there have been no randomized clinical trials to test the safety and efficacy of biologics, no reports of RP with psychiatric disorders as initial symptoms, and no reports of tocilizumab used for psychiatric symptoms due to RP. Here, we report a 60-year-old woman with mania, logomania, hallucinations, cognitive disorder, persecutory delusion, and violent tendency as chief complaints. The application of dexamethasone worsened her psychiatric symptoms. After the first infusion of tocilizumab, she achieved complete remission within one week. During the follow-up period, she sustained serological and psychiatric remission. Our case illustrates the safety and efficacy of tocilizumab for psychiatric symptoms of RP.


Effect of bond-disorder on the phase-separation kinetics of binary mixtures: A Monte Carlo simulation study.
We present Monte Carlo (MC) simulation studies of phase separation in binary (AB) mixtures with bond-disorder that is introduced in two different ways: (i) at randomly selected lattice sites and (ii) at regularly selected sites. The Ising model with spin exchange (Kawasaki) dynamics represents the segregation kinetics in conserved binary mixtures. We find that the dynamical scaling changes significantly by varying the number of disordered sites in the case where bond-disorder is introduced at the randomly selected sites. On the other hand, when we introduce the bond-disorder in a regular fashion, the system follows the dynamical scaling for the modest number of disordered sites. For a higher number of disordered sites, the evolution morphology illustrates a lamellar pattern formation. Our MC results are consistent with the Lifshitz-Slyozov power-law growth in all the cases.


A Comprehensive Review of Aliphatic Hydrocarbon Biodegradation by Bacteria.
Hydrocarbons are relatively recalcitrant compounds and are classified as high-priority pollutants. However, these compounds are slowly degraded by a large variety of microorganisms. Bacteria are able to degrade aliphatic saturated and unsaturated hydrocarbons via both aerobic and anaerobic pathways. Branched hydrocarbons and cyclic hydrocarbons are also degraded by bacteria. The aerobic bacteria use different types of oxygenases, including monooxygenase, cytochrome-dependent oxygenase and dioxygenase, to insert one or two atoms of oxygen into their targets. Anaerobic bacteria, on the other hand, employ a variety of simple organic and inorganic molecules, including sulphate, nitrate, carbonate and metals, for hydrocarbon oxidation.


Catecholamine uptake by isolated coronary arteries and atria of the kitten.
Kitten coronary arteries and atria incubated with [3H]-(-)-noradrenaline or [3H]-(+/-)-isoprenaline showed concentration- and temperature-dependent accumulation of amines (unchanged and/or as metabolites). In addition, coronary arteries incubated with [3H]-(+/-)-isoprenaline showed temperature-insensitive amine accumulation due to binding to connective tissue fibres. 2 With low concentrations of [3H]-(-)-noradrenaline (20 ng/ml) accumulation of radioactivity in both tissues was neuronal since it was reduced by desipramine, metaraminol or cocaine but not by the extraneuronal inhibitor, cortisol. 3 In coronary arteries incubated with [3H]-(+/-)-isoprenaline (5 microgram/ml) for 1 or 10 min, uptake was extraneuronal since it was inhibited by cortisol, 17beta-oestradiol or phenoxybenzamine. 4 Atria incubated with (+/-)-isoprenaline (5 to 1000 microgram/ml) showed non-neuronal, biphasic accumulation of amine. There was a high capacity, low affinity initial uptake process (apparent Km 136 micron) which was resistant to steroidal extraneuronal uptake inhibitors but which could be abolished by phenoxybenzamine. A slower uptake occurred after 2 min which was sensitive to steroidal and other extraneuronal uptake inhibitors. 5 Inhibition of uptake processes did not alter sensitivity of coronary arteries to dilator effects of catecholamines. However, experiments with extraneuronal uptake inhibitors were limited by the relaxant effects of cortisol and 17beta-oestradiol themselves. 6 In atria inhibition of neuronal uptake by desipramine or cocaine led to supersensitivity to (-)-noradrenaline but not to (-)-adrenaline or (+/-)-isoprenaline. Chronotropic responses to (-)-noradrenaline were increased five fold and inotropic responses three fold.


Hematoxylin modulates tau-RD protein fibrillization and ameliorates Alzheimer's disease-like symptoms in a yeast model.
Alzheimer's disease (AD) is one of the most serious neurodegenerative diseases with no effective treatment options available. The formation of insoluble amyloid fibrils of the hyperphosphorylated tau protein is intimately associated with AD, hence the tau protein has been a key target for AD drug development. In this work, hematoxylin was discovered as a dual functional compound, that is, acting in the inhibition of repeat domain of tau (tau-RD) protein fibrillogenesis and remodeling of pre-formed tau-RD fibrils in vitro. Meanwhile, hematoxylin was able to reduce the accumulation of tau-RD aggregates in Saccharomyces cerevisiae. Experimental and computational studies indicated that hematoxylin directly interacts with tau-RD protein through hydrophobic forces, hydrogen bonds, π-cation interactions, and π-π stackings. In addition, cellular viability assays showed that hematoxylin greatly reduced cytotoxicity induced by tau-RD aggregates. In summary, hematoxylin might be a promising candidate for further development as a potential therapeutic drug for AD patients.


Disease-dependent interaction policies to support health and economic outcomes during the COVID-19 epidemic.
Lockdowns and stay-at-home orders have partially mitigated the spread of Covid-19. However, the indiscriminate nature of mitigation - applying to all individuals irrespective of disease status - has come with substantial socioeconomic costs. Here, we explore how to leverage the increasing reliability and scale of both molecular and serological tests to balance transmission risks with economic costs involved in responding to Covid-19 epidemics. First, we introduce an optimal control approach that identifies personalized interaction rates according to an individual's test status; such that infected individuals isolate, recovered individuals can elevate their interactions, and activity of susceptible individuals varies over time. Critically, the extent to which susceptible individuals can return to work depends strongly on isolation efficiency. As we show, optimal control policies can yield mitigation policies with similar infection rates to total shutdown but lower socioeconomic costs. However, optimal control policies can be fragile given mis-specification of parameters or mis-estimation of the current disease state. Hence, we leverage insights from the optimal control solutions and propose a feedback control approach based on monitoring of the epidemic state. We utilize genetic algorithms to identify a 'switching' policy such that susceptible individuals (both PCR and serological test negative) return to work after lockdowns insofar as recovered fraction is much higher than the circulating infected prevalence. This feedback control policy exhibits similar performance results to optimal control, but with greater robustness to uncertainty. Overall, our analysis shows that test-driven improvements in isolation efficiency of infectious individuals can inform disease-dependent interaction policies that mitigate transmission while enhancing the return of individuals to pre-pandemic economic activity.


Topography of the retinal thickness in normal subjects.
A noninvasive method has been developed that is capable of providing quantitative thickness profiles of the retina. The method was used to map the retinal thickness in five normal human volunteers and determine the reproducibility of the measurements. The reproducibility or equivalent sensitivity of the measurements to detect changes was found to be 5% or 19 microns on the same day and 8% or 31 microns on different days. By averaging the values obtained in five normal subjects, ranging in age from 21 to 43 years (mean, 34 years), a preliminary normal baseline was derived for the thickness profile at the fovea and the thickness cross-section from the optic disc to the fovea. The results of the study indicated that this noninvasive method promises to be of clinical use in diagnosing ocular diseases that produce changes in the thickness of the retinal as well as in monitoring the effectiveness of therapy.


Consumer demand for caesarean sections in Brazil: informed decision making, patient choice, or social inequality? A population based birth cohort study linking ethnographic and epidemiological methods.
To investigate why some women prefer caesarean sections and how decisions to medicalise birthing are influenced by patients, doctors, and the sociomedical environment. Population based birth cohort study, using ethnographic and epidemiological methods. Epidemiological study: women living in the urban area of Pelotas, Brazil who gave birth in hospital during the study. Ethnographic study: subsample of 80 women selected at random from the birth cohort. Nineteen medical staff were interviewed. 5304 women who gave birth in any of the city's hospitals in 1993. Birth by caesarean section or vaginal delivery. In both samples women from families with higher incomes and higher levels of education had caesarean sections more often than other women. Many lower to middle class women sought caesarean sections to avoid what they considered poor quality care and medical neglect, resulting from social prejudice. These women used medicalised prenatal and birthing health care to increase their chance of acquiring a caesarean section, particularly if they had social power in the home. Both social power and women's behaviour towards seeking medicalised health care remained significantly associated with type of birth after controlling for family income and maternal education. Fear of substandard care is behind many poor women's preferences for a caesarean section. Variables pertaining to women's role in the process of redefining and negotiating medical risks were much stronger correlates of caesarean section rates than income or education. The unequal distribution of medical technology has altered concepts of good and normal birthing. Arguments supporting interventionist birthing for all on the basis of equal access to health care must be reviewed.


Organization of microtubules in axonal growth cones: a role for microtubule-associated protein MAP 1B.
Neuronal growth cones guide growing axons and dendrites (neurites) through developing embryos by detecting extrinsic guidance cues and transducing the signal into changes in motile behaviour. In this brief review, the role of the growth cone cytoskeleton in these events, in particular the microtubules, is discussed. Microtubules in the neurite are mainly bundled into fascicles whereas on entering the growth cone they diverge from each other and traverse the central (C)-domain of the growth cone. Occasionally, individual microtubules extend as far as the peripheral (P)-domain and may even enter filopodia. Microtubules in the growth cone are probably dynamically unstable, exchanging dimer with a large pool of soluble tubulin. It is proposed that the 'capture' of dynamically unstable microtubules by filopodial actin filament bundles is a crucial step underlying directed growth. Localised assembly of microtubules at the growth cone, rather than at the cell body followed by transport of polymer to the growth cone, may facilitate the delivery of material to specific regions of the growth cone and hence allow vectorial growth. Bundling of microtubules and capture of microtubules by filopodia both imply roles for microtubule-associated proteins (MAPs). Several microtubule-associated proteins are present within growth cones, including MAP 1B, MAP2 and tau. Recent experiments point toward a phosphorylated form of MAP 1B as an important component in neurite elongation and in particular in the bundling of microtubules in the growth cone.


Electrochemical denitrificaton of simulated ground water.
Electrochemical denitrification of ground water was studied with an objective to maximize nitrate transformation to nitrogen gas. Aluminum, graphite, iron and titanium were selected as electrode materials. While aluminum, iron and titanium electrodes showed 70-97% nitrate reduction, with graphite electrode the removal was only 8%. Nitrate was transformed to ammonia with iron and aluminum electrodes but with titanium electrodes nitrogen was apparently the major end product. Iron electrodes exhibited the maximum reducing condition (ORP=-463mV) and titanium showed the minimum (ORP=-206mV). Nitrate reduction with titanium electrodes was retarded in the presence of chloride ions possibly due to formation of hypochlorite ions. The first-order nitrate transformation rate constant with respect to time decreased with decrease in current density. However, when the rate constant was expressed with respect to charge passed (Coulomb/l) it was nearly same under different experimental conditions (current density and pH). The study indicates that the process might be suitable for denitrification of drinking water.


Studies on the temperature-dependent sensitivity of mouse atria to adrenergic drugs.
The sensitivity of mouse atria (chronotropic response) to beta-adrenergic receptor antagonists was examined at 37 and 26 degrees C under various experimental conditions. When isoproterenol was used as agonist, at 37 degrees C, the pA2 value (from pA2 plots) for propranolol was 8.86 and the slope of the regression line was 0.54. At 26 degrees C, the pA2 value for propranolol was 9.2 and the slope was 0.7. In the presence of tropolone, 10-5 M, the values for pA2 and slope of the regression lines were, respectively, 9.0 and 0.90 at 37 degrees C and 9.17 and 0.98 at 26 degrees C. In other words, decreasing antagonism was prevented by low temperature and tropolone. Isoproterenol was potentiated by tropolone and low temperature, but the effects of low temperature were reduced by tropolone. With sotalol as antagonist, there was greated blockade (dose ratios) of the effects of isoproterenol at 26 than at 37 degrees C. When nylidrin, a non-catecholamine, was used as agonist there was no temperature-dependent sensitivity to sotalol. Furthermore, nylidrin was not potentiated by low temperature. The data show that the observed degree of beta-receptor antagonism can be altered by changing the bath temperature and suggest that this effect is related to COMT activity or an influence of agonist disposition in the tissue.


Comparison of cardiac magnetic resonance with gated SPECT for evaluation of left ventricular function and volumes in patients with severe and multiple myocardial perfusion defects.
Gated SPECT is an accurate technique for assessment of myocardial perfusion (MP), left ventricular ejection fraction (LVEF), end-diastolic volume (EDV) and end-systolic volume (ESV). However recent studies have concluded that there are large discrepancies in assessment of LVEF and volumes by gated SPECT in patients with multiple severe myocardial perfusion defects. We sought to investigate the correlation between LVEF and volumes calculated by gated SPECT and cardiac magnetic resonance (CMR) in patients with severe multiple perfusion defects who are referred for CMR. Twenty-nine patients (20 male and 9 female, mean age: 63 years ± 11) with multiple severe fixed perfusion defects (mean 5 ± 3 segments) were referred to undergo CMR. The average time between CMR and SPECT was 4 weeks. LVEF, EDV, and ESV were derived automatically from gated SPECT. In the CMR studies, the endocardial and epicardial borders were delineated manually in the short axis planes to calculate the LVEF and volumes. The different parameters were compared using linear regression, and correlation coefficients were calculated. Substantial correlation was found between CMR and gated SPECT for EDV: r = 0.7, p < 0.001. Moderate correlation between CMR and gated SPECT for LVEF: r = 0.5, p < 0.007 and ESV r =0 .53, p < 0.003. Our data showed that the gated SPECT correlates substantially with MRI for measurement of EDV and moderately for ESV and LVEF in patients with multiple and severe perfusion defects. Thus, when accurate measurement is required, cardiac MRI is recommended.


Microtubular system in cultured mouse epithelial cells.
Previous observations had shown that colcemid does not affect locomotion of epithelial cells. Nevertheless, cultured mouse kidney cells forming epithelial sheets were found to contain a well-developed microtubular system sensitive to colcemid. The orientation of microtubules in the epithelial cells was not correlated with the stable or active state of the cell edges. It is suggested that microtubular system of the epithelial cells forming coherent sheets, in contrast to that of individually moving fibroblasts, is not essential for stabilization of the lateral cell edges.


Methylation analysis of neuraminic acids by gas chromatography-mass spectrometry.
The permethylated methyl glycoside methyl esters of N-acetyl- and N-glycolyl-neuraminic acids and of N-acetylneuraminic acid 8-acetate have been analyzed by g.1.c.-mass spectrometry. Fragmentation of the neuraminic acid derivatives in electron-impact mass spectrometry has been studied by deuterium labelling. The results were applied in the methylation analysis of neuraminic acids from gangliosides of brain and kidney.


Aspirin in cardiovascular disease.
Although other mechanisms may be contributory, the antithrombotic properties of aspirin derive predominantly from its platelet-inhibitory effects. These are mediated via irreversible acetylation of platelet cyclo-oxygenase with subsequent blockade of platelet thromboxane synthesis. Long term administration of doses of aspirin as low as 20mg daily depresses platelet thromboxane formation by more than 90%; however, higher doses appear to be necessary to prevent thromboxane-dependent platelet activation in vivo. While there is evidence of biochemical selectivity with low doses of aspirin, significant reduction of the platelet-inhibitory eicosenoid, prostacyclin, occurs even at dosages ranging from 20 to 40mg daily. The ability of aspirin to prevent the occurrence or recurrence of vaso-occlusion has been extensively investigated. In the secondary prevention of myocardial infarction 7 placebo-controlled trials involving more than 15,000 patients have been completed. The dose of aspirin varied from 300 to 1500mg daily. Although none of the individual trials produced statistically significant reductions in total or coronary mortality, taken together the results are highly suggestive of a beneficial effect of aspirin. Similarly, 2 recent studies in patients with unstable angina demonstrated a protective effect of aspirin against acute myocardial infarction and death. While each study employed widely different doses of aspirin (324mg and 1250mg daily) similar reductions in mortality were reported. The effects of aspirin on the prevention of coronary artery bypass graft occlusion have been evaluated in 9 trials. Aspirin in doses of 100 to 975mg daily was shown to be of benefit in preventing early (less than 6 months) graft occlusion, particularly when therapy was started within 24 hours of operation. In patients with prosthetic vascular grafts of the lower limbs, aspirin has been shown to reduce platelet deposition, however further controlled trials will be required to establish the patient population most likely to benefit and, as in all these studies, the optimum dose of aspirin to employ. In patients with prosthetic heart valves it is clear that aspirin alone is insufficient to prevent thromboembolic complications and when administered as an adjunct to anticoagulant therapy it is associated with a high incidence of bleeding. In contrast, there is convincing evidence from several studies for the efficacy of aspirin in doses of 990 to 1300mg daily in the prevention of stroke and death in patients with transient ischaemic attacks.(ABSTRACT TRUNCATED AT 400 WORDS)


Geranylgeranyl transferase type II inhibition prevents myeloma bone disease.
Geranylgeranyl transferase II (GGTase II) is an enzyme that plays a key role in the isoprenylation of proteins. 3-PEHPC, a novel GGTase II inhibitor, blocks bone resorption and induces myeloma cell apoptosis in vitro. Its effect on bone resorption and tumor growth in vivo is unknown. We investigated the effect of 3-PEHPC on tumor burden and bone disease in the 5T2MM model of multiple myeloma in vivo. 3-PEHPC significantly reduced osteoclast numbers and osteoclast surface. 3-PEHPC prevented the bone loss and the development of osteolytic bone lesions induced by 5T2MM myeloma cells. Treatment with 3-PEHPC also significantly reduced myeloma burden in bone. The magnitude of response was similar to that seen with the bisphosphonate, risedronate. These data show that targeting GGTase II with 3-PEHPC can prevent osteolytic bone disease and reduce tumor burden in vivo, and represents a novel approach to treating tumors that grow in bone.


Bevacizumab confers additional advantage to the combination of trastuzumab plus pertuzumab in trastuzumab‑refractory breast cancer model.
We investigated antitumor activity of trastuzumab (T)/T-DM1 + pertuzumab (P) + bevacizumab (B) in T-sensitive (BT474) and T-resistant (BT474HerR) BC models in order to test whether or not the addition of an anti-angiogenic drug can provide a supplementary advantage to the antitumor activity of double HER2–mAB combination. In addition to the antitumor activity (xenograft model), we tested antiproliferative effect, and HER2-mediated signals of different antibodies (T or P or T-DM1) in HER2-amplified T-sensitive, T-resistant and HER2-amplified/PIK3CA mutated (HCC1954) BT cell lines by 3D ON-TOP clonogenic growth assay and Western blots. Data show (1) T, T-DM1 or P blocked p-AKT (>60 %), p-ERK (>50 %) following heregulin in only T-sensitive cells, (2) T/T-DM1 + P, T/T-DM1 + B, and P + B reduced tumor growth as compared to any single-agent treatment, (3) T + P + B achieved almost complete regression of tumor growth, decreased cell proliferation, and inhibited tumor-induced angiogenesis, in both models, (4) antitumor activity of T + P + B was associated with the pharmacodynamic knockdown of p-AKT, and (5) T-DM1 + P caused complete regression of tumor volume in both models. Our data demonstrate that B imparts a significant advantage when combined with T + P in the resistant model, in contrast to T-DM1 + P, as the triple combination of T-DM1 + P + B and the double combination of T-DM1 + P showed a comparable antitumor activity. Our study reveals the preclinical evidence in favor of the inclusion of B when combined with T + P in T-resistant BC patients.


Toxicogenomics in biomarker discovery.
In the area of toxicology, the subdiscipline of toxicogenomics has emerged, which is the use of genome-scale mRNA expression profiling to monitor responses to adverse xenobiotic exposure. Toxicogenomics is being investigated for use in the triage of compounds through predicting potential toxicity, defining mechanisms of toxicity, and identifying potential biomarkers of toxicity. Whereas various approaches have been reported for the development of algorithms predictive of toxicity and for the interpretation of gene expression data for deriving mechanisms of toxicity, there are no clearly defined methods for the discovery of biomarkers using gene expression technologies. Ways in which toxicogenomics may be used for biomarker discovery include analysis of large databases of gene expression profiles followed by in silico mining of the database for differentially expressed genes; the analysis of gene expression data from preclinical studies to find differentially expressed genes that correlate with pathology (coincident biomarker) or precede pathology (leading biomarker) within a lead series; or gene expression profiling can be performed directly on the blood from preclinical studies or clinical trials to find biomarkers that can be obtained noninvasively. This chapter broadly discusses the issues and the utility of applying toxicogenomics to biomarker discovery.


Periodic breathing parameter values depend on specific pneumogram scoring criteria.
Periodic breathing (PB) has been related to both normal and pathologic respiratory system control in infants. However, comparison of the results of separate studies has been limited by the variability in procedures used by different investigators to quantify PB. In this study we scored 15 24-hr impedance pneumograms using the criteria of Parmelee et al. (Neuropediatrie 3:294-304, 1972), Christova-Gueorguieva (Biology of the Neonate 44:325-332, 1983), and Curzi-Dascalova, Kelly and Shannon (Pediatrics 63:355-360, 1979) and analyzed the resulting differences in several commonly used PB parameters. Scoring criteria consistently and significantly influenced three PB parameters: the %PB, number of episodes of PB/100 min recording time, and mean duration of PB episode length showed average changes of 74%, 179%, and 36%, respectively, when the methods with the most extreme differences were compared. In contrast, the duration of the longest episode of PB showed no significant change as a function of scoring criteria. Awareness of the particular method of PB scoring is therefore essential in interpreting PB parameter values.


Normative video head impulse test data in subjects with and without vascular risk factors.
There is a paucity of age- and vascular risk factor-stratified video head impulse test (vHIT) vestibulo-ocular reflex (VOR) data in the literature. The aim of this study was to investigate the vHIT VOR properties in healthy subjects of different ages and subjects with vascular risk factors. This was a prospective observational single-center study at a tertiary referral university hospital in northern Sweden. Healthy participants and subjects with vascular risk factors were investigated with a floor standing external camera vHIT device. Age-stratified mean VOR gain among healthy adults and between group gain and gain asymmetry differences were calculated. We included eighty-eight healthy adults with a mean (range) age of 50 (22-85) years and n = 48 stroke ward patients with vascular risk factors (but without vestibular disease) with a mean (range) age of 74 (42-92) years. The mean VOR gain of horizontal canals decreased at higher ages in healthy subjects (r = - 0.32, p < 0.01, n = 167 canals). The age-stratified mean (SD) VOR gains were < 30 years: 0.98 (0.07), 30-39 years: 0.97 (0.07), 40-49 years: 0.98 (0.06), 50-59 years: 0.99 (0.06), 60-69 years: 0.93 (0.08), ≥ 70 years: 0.89 (0.15). No consistent differences between healthy subjects and subjects with vascular risk factors were seen except for a trend towards more pronounced gain asymmetries in the latter group. Age, but not vascular risk factors influence VOR gain. Age-adjusted vHIT-measurements may be useful in acute vertigo stroke risk differentiation.


Future direction for evaluation and evaluation research in health care: the nursing perspective.
In planning for the future, nurses should consider: differences and similarities between evaluation and evaluation research; program evaluation implications for nursing as well as for nurse researchers; and policy decisions and issues in evaluation research.


Influence of rain, tidal wetting and relative humidity on release of carbon dioxide by standing-dead salt-marsh plants.
Dead parts of salt-marsh plants form a considerable fraction of their annual average standing crop. A microbial assemblage living on and in the standing-dead leaves and stems of Spartina alterniflora and Juncus roemerianus responds to saltwater, freshwater or water-vapor wetting by immediately beginning to release CO2. Water-saturated, standing-dead leaves and culms of S. alterniflora release CO2 at steady rates of as much as about 200 and 140 μg CO2-C·g-1 dry·h-1, respectively, at temperatures of 25-30°C, after an initial burst of higher rates. These CO2-release rates are within the range of maximal rates reported for decaying terrestrial litter, and are as high as most rates reported for S. alterniflora decaying under continuously wetted or submerged conditions.


Evaluation of a behavioural intervention to reduce perioperative midazolam administration to older adults.
Older patients commonly receive benzodiazepines during anaesthesia despite guidelines recommending avoidance. Interventions to reduce perioperative benzodiazepine use are not well studied. We hypothesized an automated electronic medical record alert targeting anaesthesia providers would reduce administration of benzodiazepines to older adults undergoing general anaesthesia. We conducted a retrospective study of adults who underwent surgery at 5 hospitals within one US academic health system. One of the hospitals received an intervention consisting of provider education and an automated electronic medical record alert discouraging benzodiazepine administration to patients aged 70 years or older. We used difference-in-differences analysis to compare patterns of midazolam use 12-months before and after intervention at the intervention hospital, using the 4 non-intervention hospitals as contemporaneous comparators. The primary analysis sample included 20,347 cases among patients aged 70 and older. At the intervention hospital, midazolam was administered in 454/4,240 (10.7%) cases pre-alert versus 250/3,750 (6.7%) post-alert (p<0.001). At comparator hospitals, respective rates were 3,186/6,366 (50.0%) versus 2,935/5,991 (49.0%) (p=0.24). After adjustment, the intervention was associated with a 3.2 percentage point (p.p.) reduction in the percentage of cases with midazolam administration (95% CI: (-5.2, -1.1); p=0.002). Midazolam dose was unaffected (adjusted mean difference -0.01 mg, 95% CI: (-0.20, 0.18); p=0.90). In 76,735 cases among patients aged 18-69, the percentage of cases with midazolam administration decreased by 6.9 p. p. (95% CI: (-8.0, -5.7); p<0.001). Provider-facing alerts in the intraoperative electronic medical record, coupled with education, can reduce midazolam administration to older patients presenting for surgery but may affect care of younger patients.


Phantoms in the mortuary--DNA transfer during autopsies.
DNA evidence frequently plays an important role in criminal investigations and in some cases may be the only means of convicting a suspect. The constant improvement of DNA analysis techniques affords the individualization of minute amounts of DNA, aggravating the risk of contamination artifacts. In our study, we investigated the prevalence of DNA contamination in the autopsy facilities of the Institutes of Legal Medicine in Essen and Kiel (Germany). Using DNA-free swabs, we took samples from instruments used during autopsy and autopsy tables. Surfaces and instruments were routinely cleaned before sampling. Swabs were subjected to different PCRs to quantify the total amount of DNA and to amplify individual specific STR-markers. In most samples, alleles that could be linked to bodies that had been autopsied before were found. Furthermore, we could show that a DNA transfer from the autopsy table to a body was detectable in four out of six cases investigated. The interpretation of DNA typing results may thus be severely complicated. To avoid DNA contamination, we tried out different cleaning methods, of which only a bleach containing cleaner showed sufficient results.


Behavior and lifestyle characteristics of male Kuwaiti drivers.
The high traffic accident risk among young drivers is a well-known and well-documented fact in most countries. Lifestyle has proven to affect driving behavior as well as accident risk. This study covers the lifestyle component of the problems related to young male Kuwaiti drivers' accident risk. The purpose of the study is to measure the relationship between lifestyle and accident risk. Lifestyle is measured through a questionnaire, where 302 male Kuwaiti drivers (mean age=28 years; range 25-35 years) answer 39 questions related to behavioral and social factors, road conditions, police enforcement, and life satisfaction. They also report their involvement in accidents and traffic violations. The questionnaire's validity and reliability (Cronbach's alpha=0.7) were achieved. Principal component analysis reduced the 39 items on the questionnaire to 5 factors. Inadequate police enforcement is strongly correlated (r=0.862) to accident risk and traffic violations and is thus considered the best predictor of traffic accidents in Kuwait. As driving-related incidents (on-the-job and off-the-job) are a significant source of fatalities and lost-work-days, the study points to the importance of considering cultural factors in the design of comprehensive safety programs for industry.


Testicular involution following optic enucleation: the Leydig cell.
The testes of Syrian hamsters underwent pronounced involution within six weeks after blinding. The seminiferous tubules were devoid of all stages of spermatid development and mature spermatozoa were absent from the tubule lumina. The diameter of of the Leydig cells was 25% less than that of controls. Examination with the electron microscope revealed thick bundles of collagen fibrils interspersed between Leydig cells and surrounding Leydig cells in the blinded hamsters. The Leydig cell nuclei were shrunken and highly infolded. Lipid droplets that were often seen in normal Leydig cells were absent in the involuting Leydig cells. The size of the Golgi complex and the amount of smooth endoplasmic reticulum were reduced. Results of the present experiment confirm that inactivity of the Leydig cells is the reason for the decline in serum testosterone levels in blinded hamsters.


Prophylactic antiemetic effect of midazolam after middle ear surgery.
To investigate the prophylactic antiemetic effect of midazolam after middle ear surgery. A prospective, randomized, double-blind, placebo-controlled study. Ninety women patients undergoing middle ear surgery with general anesthesia received intravenously either midazolam 0.075 mg/kg or normal saline (n = 45 each) after induction of anesthesia. The incidence and severity of postoperative nausea and vomiting, rescue antiemetics, pain intensity, and side effects such as headache, dizziness, and drowsiness were assessed during the first 24 hours after anesthesia. Midazolam groups showed total incidence and severity of nausea and vomiting. Patients who required rescue antiemetics were significantly lower than in saline group (P < 0.05), but there were no significant differences in pain intensity and side effects such as headache, dizziness, and drowsiness between groups. Midazolam 0.075 mg/kg is effective for reducing nausea and vomiting after middle ear surgery.


[Heart rate variability in patients with hypertension and type 2 diabetes treated with long acting calcium antagonists].
Enhanced sympathetic activity is a potential cause of increased risk of cardiovascular complications during treatment of hypertension and type 2 diabetes. Heart rate variability (HRV) was assessed before and after 12-16 weeks of treatment with calcium antagonists in 89 patients with mild and moderate hypertension. Changes of majority of parameters of 24 hour blood pressure monitoring were in general favorable however lowering of magnitude and rate of morning blood pressure rise was observed only in verapamil treated patients. Analysis of HRV showed that treatment with all long acting calcium antagonists under study was associated with enhancement of sympathetic activity. In supine position nifedipine treated compared with verapamil treated patients exhibited greater sympathetic activity. In upright position changes of HRV parameters characteristic for increased sympathetic activity were also more pronounced in dihydropyridine treated compared with verapamil treated patients. Effect of calcium antagonists on parameters of HRV is negative and this should be taken into consideration when antihypertensive treatment of patients with hypertension and type 2 diabetes is selected.


Effects of diltiazem on left ventricular diastolic behavior in patients with hypertrophic cardiomyopathy: evaluation with exercise pulsed Doppler echocardiography.
To estimate the effects of diltiazem on the left ventricular diastolic abnormalities in patients with hypertrophic cardiomyopathy, transmitral flow velocity during diastole was studied before and immediately after dynamic leg exercise with the pulsed Doppler technique combined with two-dimensional echocardiography. Seventeen patients with hypertrophic cardiomyopathy and 24 apparently healthy men performed bicycle ergometer exercise in the supine position with the target heart rate set at 120 beats/min. The patients with cardiomyopathy were directed to perform the exercise at the same intensity after receiving 30 to 60 mg of diltiazem, three times daily, for 1 or 2 weeks. The pattern of transmitral flow velocity in diastole had two components, one corresponding to the rapid filling phase in early diastole and the other to the atrial contraction phase in late diastole. To assess left ventricular diastolic behavior, the following variables were analyzed: peak velocity in the rapid filling and atrial contraction phases, the ratio of peak velocity in the atrial contraction phase to that in the rapid filling phase, and pressure half-time. The changes in peak velocity in the atrial contraction phase, pressure half-time and the ratio of peak velocity in the atrial contraction phase to that in the rapid filling phase with exercise differed significantly between patients with hypertrophic cardiomyopathy with no medication and control subjects. After diltiazem, the response of these variables to exercise was almost identical in the two groups. These results suggest that diltiazem can lessen the left ventricular diastolic abnormality in patients with hypertrophic cardiomyopathy on dynamic exercise of mild intensity.