Antennal grooming facilitates courtship performance in a group-living insect, the German cockroach Blattella germanica.
The antennae of adult male German cockroaches detect a contact sex pheromone embedded in the female's cuticular lipids. The female pheromone stimulates courtship behavior in males, notably a wing-raising (WR) display. Within aggregations, however, cuticular lipids are disseminated by contact among group members, including nymphs and adults of both sexes, and "contamination" of cockroaches with the cuticular lipids of another stage or sex may interfere with sex discrimination and disrupt courtship. We used behavioral observations, bioassays and chemical analysis to determine how males maintain their sensitivity to sex pheromone in aggregations. Males contaminated with female pheromone displayed lower courtship, because residual female pheromone on their antennae adapted their peripheral sensilla and habituated the central nervous system. Female pheromone that contaminated the male's antennae also elicited courtship from other non-contaminated males, disrupting their sex discrimination in the group. However, antennal grooming effectively removed female pheromone from males' antennae and maintained their chemosensory acuity and sexual discrimination among group members. Thus, grooming of the antennae and other sensory appendages is an important strategy to enhance sensory acuity, especially in group-living insects like the German cockroach.


Effective Conservation.
Effective altruism is a growing humanitarian movement with a track record of success in evaluating the effectiveness of charitable spending across a wide range of projects. We suggest ways in which the foundations of this movement can be applied to the complex world of conservation.


Cerebral Aneurysm Associated with an Arachnoid Cyst: 3 Case Reports and a Systematic Review of the Literature.
Arachnoid cysts and intracranial aneurysms are not rare, but it is unusual for an aneurysm to be associated with an arachnoid cyst. The objective of this study was to reveal the association between arachnoid cysts and intracranial aneurysms. Methods included to report 3 cases with these 2 pathologies and to perform a systematic review of the English and Japanese literature using PubMed, Scopus, and Ichushi Web. The first case was of a 46-year-old man with a subarachnoid hemorrhage on the basal cistern and bilateral arachnoid cysts in the middle fossa, the second was that of a 29-year-old woman with a subarachnoid hemorrhage at the basal cistern and an arachnoid cyst in the left middle fossa, and the third was that of a 60-year-old man with a right putaminal hemorrhage and contralateral unruptured aneurysm and arachnoid cyst. A literature search for similar cases found 27 patients. It was difficult to diagnose a ruptured aneurysm in some cases with an arachnoid cyst because computed tomography scan showed atypical findings, such as no hemorrhage, intracystic localized hemorrhage, or subdural hematoma. This review revealed that aneurysms and arachnoid cysts were significantly located ipsilaterally and that they occurred together in relatively young patients.


Role of histamine in traumatic brain edema. An experimental study in the rat.
The possibility that histamine plays a role in the formation of traumatic brain edema was investigated in the rat. A 3 mm deep and 3 mm long stab injury was performed in the right parietal cortex under urethane anaesthesia. The brain water content and histamine levels in plasma and brain were measured at the end of 1, 2 and 5 h periods after trauma. There was a 3.46% increase in brain water content in the traumatized hemisphere from the value in the control group at 5 h. The histamine content was increased by 107% in plasma and 51% in the traumatized brain hemisphere from the control value at this time period. The increased brain water content as well as the elevated plasma and brain histamine levels were prevented by prior treatment with the histamine H2-receptor antagonist cimetidine. Mepyramine (a histamine H1-receptor antagonist) failed to reduce the increased brain water content and the histamine levels in plasma and brain remained high. The results strongly indicate that histamine has a role in the formation of early traumatic brain edema and that this reaction can be influenced by pharmacological procedures.


Indirect Immunofluorescence for the Detection of Autoimmune Urticaria.
An autoimmune basis is believed to be responsible for about half of chronic spontaneous urticaria (CSU) cases. The autologous serum skin test is used as a possible indicator, but there is currently no test that directly indicates an autoimmune etiology. In this study, an indirect immunofluorescence was used to identify patients with autoantibodies directed at mast cells. Two substrates were used including paraffin embedded sections of skin biopsies from an infant with bullous mastocytosis and cord blood-derived mast cells (CBMC). Sera from 76 patients with CSU were incubated with substrates and conjugated with human IgG. Using the bullous mastocytosis preparations, positive indirect immunofluorescence was found in 46% (n = 76), while the CBMC substrate was positive in 39% (n = 70). The IgG autoantibodies directed at mast cells could be detected in about half the patients with CSU. Indirect immunofluorescence should be considered as an indicator of the autoimmune form of CSU.


Myocardial blood flow and oxygen consumption after aortic cross-clamping.
The effect of four repetitive periods of 10 min global ischemia, followed by 15 min of reperfusion on myocardial blood flow and oxygen consumption at 34 degrees C (group N) and 25 degrees C (group H) were studied in comparison with that of 60 min continuous ischemia combined with multidose St. Thomas Cardioplegia (group C) in dogs on cardiopulmonary bypass (CPB). Two groups, in which a protocol comparable to the groups N and H, respectively, but without repetitive periods of ischemia was followed, served as control. In all groups a hyperemic response was observed after release of aortic cross-clamping (AC). Myocardial blood flow was not diminished at the end of CPB as compared to the values at the start of CPB. We conclude that the no-reflow phenomenon did not occur after these procedures of intermittent or continuous AC. Immediately following release of AC the arterial-coronary sinus difference of oxygen content reached a peak value in groups N and H indicating rapid replenishment of the low tissue oxygen content. These peak values appeared to be much smaller after cardioplegia. After 10 min of reperfusion a significant lower oxygen consumption was observed at 25 degrees C (0.2 mumole.g-1.min-1 O2) as compared to 34 degrees C (1.5 mumole.g-1.min-1 O2). This difference cannot be explained by temperature alone because oxygen consumption did not decrease below 0.5 mumole.g-1.min-1 in the control group of dogs put on CPB at 25 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)


RSV infection-elicited high MMP-12-producing macrophages exacerbate allergic airway inflammation with neutrophil infiltration.
Respiratory syncytial virus (RSV) infection often exacerbates bronchial asthma, but there is no licensed RSV vaccine or specific treatments. Here we show that RSV-induced alveolar macrophages, which produce high levels of matrix metalloproteinase-12 (MMP-12), exacerbate allergic airway inflammation with increased neutrophil infiltration. When mice subjected to allergic airway inflammation via exposure to the house dust mite antigen (HDM) were infected with RSV (HDM/RSV), MMP-12 expression, viral load, neutrophil infiltration, and airway hyperresponsiveness (AHR) were increased compared to those in the HDM and RSV groups. These exacerbations in the HDM/RSV group were attenuated in MMP-12-deficient mice and mice treated with MMP408, a selective MMP-12 inhibitor, but not in mice treated with dexamethasone. Finally, M2-like macrophages produced MMP-12, and its production was promoted by increase of IFN-β-induced IL-4 receptor expression with RSV infection. Thus, targeting MMP-12 represents a potentially novel therapeutic strategy for the exacerbation of asthma.


Incidental auditory learning and memory-guided attention: Examining the role of attention at the behavioural and neural level using EEG.
The current study addressed the relation between awareness, attention, and memory, by examining whether merely presenting a tone and audio-clip, without deliberately associating one with other, was sufficient to bias attention to a given side. Participants were exposed to 80 different audio-clips (half included a lateralized pure tone) and told to classify audio-clips as natural (e.g., waterfall) or manmade (e.g., airplane engine). A surprise memory test followed, in which participants pressed a button to a lateralized faint tone (target) embedded in each audio-clip. They also indicated if the clip was (i) old/new; (ii) recollected/familiar; and (iii) if the tone was on left/right/not present when they heard the clip at exposure. The results demonstrate good explicit memory for the clip, but not for tone location. Response times were faster for old than for new clips but did not vary according to the target-context associations. Neuro-electric activity revealed an old-new effect at midline-frontal sites and a difference between old clips that were previously associated with the target tone and those that were not. These results are consistent with the attention-dependent learning hypothesis and suggest that associations were formed incidentally at a neural level (silent memory trace or engram), but these associations did not guide attention at a level that influenced behaviour either explicitly or implicitly.


Induction of the interleukin-2/15 receptor beta-chain by the EWS-WT1 translocation product.
EWS-WT1 is a chimeric transcription factor resulting from fusion of the N-terminal domain of the Ewing sarcoma gene EWS to the three C-terminal zinc fingers of the Wilms tumor suppressor WT1. This translocation underlies desmoplastic small round cell tumor (DSRCT), which is noted for the abundance of reactive stroma surrounding islets of tumor cells, suggestive of paracrine signals contributing to tumor cell proliferation. Hybridization to high-density oligonucleotide microarrays can be used to identify targets of EWS-WT1. Expression of EWS-WT1 from a tetracycline-regulated promoter leads to the induction of growth-associated genes, of which the most remarkable is the beta-chain of the interleukin-2/15 receptor (IL-2/15Rbeta). Potent transcriptional activation by the chimeric protein maps to two bindings sites within the IL-2/15Rbeta promoter. Analysis of primary DSRCT tumor specimens demonstrates high levels of IL-2/15Rbeta within the tumor cells, along with expression of IL-2 and IL-15 by the abundant hyperplastic endothelial cells within the reactive stroma. Activation of this cytokine signaling pathway is consistent with the nuclear localization of its downstream effectors, phosphorylated STAT3 and STAT5. These observations suggest that the transcriptional induction of a cytokine receptor by a tumor-associated translocation product enables a proliferative response of epithelial cancer cells to ligands secreted by the surrounding stroma.


Intravascular ultrasound assessment of drug-eluting stent coverage of the coronary ostium and effect on outcomes.
When stenting an ostial or proximal coronary lesion, 1 fundamental decision is whether to extend the proximal end of the stent into the aorta (in the case of the left main [LM] or right coronary ostium) or into the polygon of confluence of the LM (in the case of the left anterior descending [LAD] ostium). Complete angiographic and intravascular ultrasound data and 9-month follow-up angiographic and clinical data were available from 459 patients with 138 ostial lesions (angiographic diameter stenosis within the ostium of ≥50%) or 321 nonostial lesions in which the proximal end of the stent ended at or near the coronary ostium. Strut protrusion was more frequent in the LM than in the right or LAD ostium (68% vs 59% vs 53%, p = 0.010). The length of strut protrusion was 3.4 ± 1.7 mm in the LM ostium, 1.7 ± 1.0 mm in the LAD ostium, and 2.4 ± 1.4 mm in the right ostium (p = 0.001). In contrast, incomplete stent coverage of the ostium was similar among the LM, LAD, and right coronary artery (23% vs 33% vs 28%, p = 0.084) with a residual uncovered segment plaque burden of 42 ± 11%. Ostial restenosis was similar between the lesions with versus without strut protrusion (3.2% vs 2.3%, p = 0.775) and between the lesions with incomplete versus complete stent coverage of the ostium (2.4% vs 3.0%, p = 0.100). Ostial restenosis was seen in only 2 of 61 lesions (3.3%) with acute malapposition. In conclusion, when treating an ostial or proximal coronary artery lesion with a drug-eluting stent, the decision of whether to protrude the proximal end of the stent or leave the ostium uncovered does not appear to be critical.


Association between Histone Deacetylase 9 Gene Polymorphism and Stroke in Chinese Han Population.
To explore the correlation between the polymorphism of histone deacetylase 9 gene (rs1060499865, rs723296, rs957960) and ischemic stroke (IS) in Chinese Han population in Dali region. This study included 155 IS patients and 128 healthy physical examinees. TaqMan-polymerase chain reaction technology and multivariate logistic regression were performed. In the case group, there was no polymorphism of rs1060499865 observed in the two groups; whereas on the rs723296 locus the frequencies of C allele and TC genotype were significantly higher than that in the control group, alleles C and T were associated with a 2.158-fold increase in IS risk, and genotypes TC and TT were associated with a 2.269-fold increase in IS risk. The locus rs957960 exhibited no significant difference between the two groups. An association between rs723296 and the risk of IS was found in the Chinese Han population in Dali region. No significant association was found between rs1060499865, rs957960 and IS in the Chinese Han population in Dali region.


Metabolite profiling in human urine by LC-MS/MS: method optimization and application for glucuronides from dextromethorphan metabolism.
Analysis of human urine for specific compounds or metabolites is an established method for biomonitoring occupational or environmental exposures. Modern liquid chromatography-tandem mass spectrometry is not limited to single compounds but can simultaneously analyze whole classes of urine constituents with both high sensitivity and specificity. Individual differences in the composition of urine are very large in humans, which raises a number of problems that are not encountered in animal experimentation. In this report, we investigated whether analysis of glucuronides as a class could reflect differences between human individuals regarding the polymorphic activity of the cytochrome P450 enzyme CYP2D6. From a group of 152 students that had been classified for CYP2D6 activity, urine of 12 "poor metabolizers" and 35 "extensive metabolizers" was collected 90 min after ingestion of 10mg of the antitussive drug dextromethorphan (DEX) and analyzed for glucuronides. Methods development included the following aspects: adjustment of urine samples to equal creatinine concentration to avoid differences between samples in retention times and ion suppression; on-line enrichment of low-level analytes by column switching; precursor ion scan vs. theoretical multiple reaction monitoring; use of quality control samples to check for reproducibility in large sample series; peak extraction and handling of null entries to build the data matrix; logarithmic data transformation and different scaling procedures; principal component analysis (PCA) vs. discriminant analysis. Our results show that an optimized procedure not only identified the known DEX metabolites as predictors of CYP2D6-specific metabolic pathways but also indicated the presence of additional, so far unknown path-specific glucuronide metabolites. We conclude that metabolite profiling of urine and other biofluids by modern mass spectrometric methodology may help characterize individual differences and become useful in drug development and personalized pharmacotherapy.


Nocturia is associated with an increased risk of coronary heart disease and death.
What's known on the subject? and What does the study add? Nocturia has been associated with multiple chronic conditions, however, previous studies have been conducted only at a single time. We found that nocturia preceded the development CHD in young men. Moderate nocturia may be an early marker of CHD in young men. To determine whether nocturia is associated with the development of diabetes mellitus, hypertension, coronary heart disease (CHD) and occurrence of death. We studied data obtained from a retrospective cohort of randomly selected men, aged 40-79 years in 1990, from Olmsted County, MN, USA. Moderate nocturia was defined as waking to urinate ≥2 times per night. Men were followed every 2 years through repeated questionnaires and community medical records to assess development of diabetes mellitus and hypertension, and occurrence of death. CHD was ascertained through ongoing surveillance of heart disease in Olmsted County. Cox proportional hazard models were used to estimate associations between baseline nocturia and each of the outcomes. A total of 2447 men were followed for a median of 17.1 years (25th and 75th percentiles: 15.0, 17.4 years). Moderate nocturia was not significantly associated with the later development of diabetes mellitus or hypertension in this study. Younger men (<60 years of age) with moderate nocturia were more likely to develop CHD later in life than younger men without nocturia (hazard ratio [HR]: 1.68; 95% confidence interval [CI]: 1.13, 2.49). This association was no longer significant when adjusted for age, body mass index (BMI) and urological medications (HR: 1.36; 95% CI: 0.87, 2.12). Older men (≥60 years of age) with moderate nocturia were more likely to die than older men without moderate nocturia, even after adjusting for age, BMI, urological medications and CHD (HR: 1.48; 95% CI: 1.15, 1.91). Nocturia may be a marker for increased risk of CHD in younger men, and death in older men.


Transcranial Parenchymal Sonographic Findings in Patients With Cerebral Small Vessel Disease: A Preliminary Study.
Patients with cerebral small vessel disease often present with various motor, cognitive, and emotional changes, including gait disturbances, parkinsonism, and depression. Substantia nigra hyperechogenicity, brain stem raphe hypoechogenicity, ventricle diameters, and sonographic characteristics of other brain structures on transcranial sonography have been increasingly used as biomarkers in a range of neurologic diseases. We aimed to explore the frequency and clinical correlates of transcranial sonographic findings in symptomatic patients with small vessel disease. In a cross-sectional study, neurologic, cognitive, and emotional statuses and transcranial sonographic and magnetic resonance imaging findings were compared between 102 patients with small vessel disease and 45 healthy age- and sex-matched control participants. Compared to healthy controls, small vessel disease cases had more frequent brain stem raphe hypoechogenicity (55.9% versus 11.1%; P < .0001), substantia nigra hyperechogenicity (30.4% versus 11.1%; P = .022), and enlarged third ventricles (P < .0001). Substantia nigra hyperechogenicity correlated with gait disturbances, extrapyramidal features, and cognitive impairment. Brain stem raphe hypoechogenicity was associated with the diagnosis of depression. Enlargement of the third and lateral ventricles was more frequent in patients with cognitive impairment. Pathologic substantia nigra hyperechogenicity and enlarged ventricles were associated with the severity of cerebral ischemic lesions. Transcranial sonography shows pathologic findings in a substantial number of patients with small vessel disease, probably reflecting disruption of frontostriatal pathways.


Synthesis and properties of prodrugs activated in hypoxia to give bleomycin analogues.
Prodrugs bioreductively activated to bleomycin analogues are reported. The production of hydroxyl radicals in the presence of FE(II) and dioxygen by both the prodrugs and the activated products are determined and their in vitro cytotoxicity measured.


Genetically predicted childhood body mass index and lung cancer susceptibility: A two-sample Mendelian randomization study.
The association between adult body mass index (BMI) and lung cancer (LC) susceptibility have been reported, but the causal relationship with childhood BMI remains largely unclear. To evaluate the causal effect of childhood BMI on LC susceptibility, a two-sample Mendelian randomization (MR) study was performed. The two-sample MR analysis utilized 25 single nucleotide polymorphisms (SNPs) as instrumental variables for childhood BMI. Genetic summary data from the International Lung Cancer Consortium and FinnGen databases were analyzed to estimate the causal effect of these SNPs on LC susceptibility. The IVW method was employed as the primary analysis, supplemented by the Weighted Median, MR-Egger, and MR pleiotropy residual sum and outlier test. Our findings indicated that there was no causal association between childhood BMI and the susceptibility of LC (odds ratio [OR]: 1.03, 95% confidence interval [CI]: 0.90-1.17, p = 0.705), lung adenocarcinoma (OR: 0.99, 95% CI: 0.86-1.13, p = 0.832), lung squamous cell carcinoma (OR: 0.97, 95% CI: 0.84-1.13, p = 0.726), and small cell LC (OR: 1.09, 95% CI: 0.82-1.45, p = 0.554) based on the IVW as well as other methods employed. Furthermore, these findings indicated no causal effect of childhood BMI on the LC susceptibility in both ever smokers and never smokers. This study did not conclude a causal effect between childhood BMI and LC susceptibility. However, given the complex nature of cancer development, further studies are needed to verify these findings.


Treatment of severe bacillary dysentery with trimethoprim alone.
Trimethoprim (300 mg twice daily for five days) and co-trimoxazole (two tablets twice daily for five days) were compared as treatment for adult patients with severe shigellosis in Rwanda. Excellent bacteriological and clinical results were obtained with both regimens, with the exception of patients infected with a trimethoprim-resistant strain of Shigella dysenteriae type 1. Since only 20 patients were investigated, the conclusions of our study do not reach statistical significance. Before recommending trimethoprim as standard therapy for shigellosis, the validity of our results should be tested in a larger trial and the long-term ecological consequences of monotherapy carefully monitored.


Auditory and visual word processing studied with fMRI.
Brain activations associated with semantic processing of visual and auditory words were investigated using functional magnetic resonance imaging (fMRI). For each form of word presentation, subjects performed two tasks: one semantic, and one nonsemantic. The semantic task was identical for both auditory and visual presentation: single words were presented and subjects determined whether the word was concrete or abstract. In the nonsemantic task for auditory words, subjects determined whether the word had one syllable or multiple syllables. In the nonsemantic task for visual words, subjects determined whether the word was presented in lower case or upper case. There was considerable overlap in where auditory and visual word semantic processing occurred. Visual and auditory semantic tasks both activated the left inferior frontal (BA 45), bilateral anterior prefrontal (BA 10, 46), and left premotor regions (BA 6) and anterior SMA (BA 6, 8). Left posterior temporal (middle temporal and fusiform gyrus) and predominantly right-sided cerebellar activations were observed during the auditory semantic task but were not above threshold during visual word presentation. The data, when averaged across subjects, did not show obligatory activation of left inferior frontal and temporal language areas during nonsemantic word tasks. Individual subjects showed differences in the activation of the inferior frontal region while performing the same task, even though they showed similar response latency and accuracy.


High-risk factors associated with refractory childhood bacterial meningitis in Southwest China.
Refractory bacterial meningitis is acute, develops rapidly, and has higher mortality and morbidity than common bacterial meningitis. This study was undertaken to investigate the high-risk factors related to refractory bacterial meningitis in children with positive pathogens. We retrospectively analyzed the clinical data of 109 patients who had bacterial meningitis. The patients were divided into a refractory group (96 patients) and nonrefractory group (13 patients) based on the classification criteria. Seventeen clinical variables on risk factors were extracted and evaluated by univariate and multivariate logistic regression analyses. There were 64 males and 45 females. The onset age ranged from 1 month old to 12 years old, and the median age was 181 days old. The pathogenic bacteria included 67 cases of gram-positive (G+) bacteria (61.5%) and 42 cases of gram-negative (G-) bacteria. In patients who were 1 to 3 months old, E. coli was the most common (47.5%), followed by Streptococcus agalactiae and Staphylococcus hemolyticus (10.0%); in patients > 3 months old, S. pneumoniae was the most common (55.1%), followed by E. coli (8.7%). The multivariate analysis indicated that consciousness disorder (odds ratio [OR] = 13.050), peripheral blood C-reactive protein (CRP) ≥ 50 mg/L (OR = 29.436), and the isolate bacteria being gram-positive bacteria (OR = 8.227) were independent risk factors for predicting who would progress to refractory bacterial meningitis in this group. For patients who have pathogenic positive bacterial meningitis along with consciousness disorder, CRP ≥ 50 mg/L, and/or have an isolate bacteria that is a G + bacteria, it is important to be alert to the potential for progression to refractory bacterial meningitis, which demands the physicians' significant attention.


beta-Glucuronidase levels in patients with fibrocystic breast disease.
Certain enzymes in tissues and body fluids may, through reversal of the detoxification process, influence the composition and availability of steroid hormones, toxins, and carcinogens. The ubiquitous enzyme beta-glucuronidase, which hydrolyzes glucuronide conjugates, thereby reversing one of the main detoxification and excretion pathways, was found to vary in concentration in different cysts over a 300-fold range. The distribution was a continuum, devoid of discrete sub-populations. Evidence obtained on selected cyst fluids of high and low beta-glucuronidase activities indicated that the level of the enzyme significantly influenced the ratio of unconjugated: glucuronidated estradiol. The patients with fibrocystic breast disease fell into 2 distinct subpopulations on the basis of their serum beta-glucuronidase activity. In one group the activity was near normal, while in the second group the average serum beta-glucuronidase activity was 3-fold higher than in the women who did not have benign breast disease.


The flash visual evoked potential-P2 and the detection of amnestic mild cognitive impairment: A review of empirical literature.
Amnestic Mild Cognitive Impairment (aMCI) is now recognized as an early risk state for the development of Alzheimer's dementia (AD). Biomarkers, including those that are cerebrospinal fluid or brain imaging based, have yet to provide the ultimate marker variable. A need currently exists for a non-invasive, easy to administer biomarker that contains aMCI/AD specific pathognomic information. The objective of the present investigation was to provide an updated review of the Flash Visual Evoked Potential-P2 (FVEP-P2) as a biomarker for aMCI and AD. The FVEP-P2 has been shown to possess AD specific pathognomic information. A review was conducted of all articles published between the years 1976 and 2019 that examined the clinical utility of the FVEP-P2 in the diagnosis of aMCI or AD. Only 17 published investigations met the criteria of the review. The weighted average effect size, as measured by Cohen's d, was 1.07, with patients diagnosed with either aMCI or AD exhibiting a significant delay in the FVEP-P2 latency. The weighted mean latency for the controls was 143.92 ms (SD = 17.13). The weighted mean latency for the aMCI/AD was 164.02 ms (SD = 21.33). Estimates of sensitivity, specificity, and accuracy were based on the weighted means and standard deviations and were equal to 0.73. The area under the curve was equal to 0.78. The results of the current review suggest that the FVEP-P2 latency possesses AD specific pathognomic information and that it should be included as part of a much larger assessment process that includes neuropsychological, cerebrospinal fluid, and brain imaging findings.


Automatic analysis of the EMG interference pattern.
A method is described for the automatic analysis of EMG interference patterns obtained at optional non-controlled force levels. It is a modification of Willison's method of measuring turns and amplitude of the signal. In the method, the mean amplitude is plotted against turns obtained during 300 msec for each of 20 recording sites. Different voluntary strengths are used and a scatter of points is obtained. Confidence limits enclosing these points are constructed for healthy subjects for 4 different muscles with concentric and monopolar electrodes. The normal values differ with age, muscle, sex and electrode. The method is tested on patients with myopathic or neurogenic EMG and a high diagnostic yield is obtained. The method is objective, reproducible, fast and needs relatively small computer facilities.


Amino acids in SRS1 and SRS6 are critical for furanocoumarin metabolism by CYP6B1v1, a cytochrome P450 monooxygenase.
CYP6B1v1 is the principal cytochrome P450 monooxygenase (P450) that detoxifies dietary furanocoumarins in the guts of Papilio polyxenes, the black swallowtail caterpillar. Sequence alignments and structure comparisons of CYP6B1v1 with the mouse CYP2A5 and bacterial CYP102 proteins, which are also capable of metabolizing the linear furanocoumarin xanthotoxin (8-methoxypsoralen), suggested that Phe116, His117, Val368 and Phe484 might be active site residues. In a homology model developed for CYP6B1v1, the side chains of Phe116 and His117 located in the B'-C loop of SRS1 are predicted to be positioned above the haem plane, while the side chain of Phe484 located in SRS6 is predicted near the entrance of the catalytic pocket. Site-directed mutagenesis of residues Phe116, His117 and Phe484 indicated that these residues represent several of those that determine this protein's stability and substrate specificity. Whereas all aromatic mutants of Phe116 and Phe484 generated CO-difference spectra with maxima at 450 nm indicative of correctly configured monooxygenases, aromatic mutants of Phe116 exhibited reduced reactivities toward some furanocoumarins and aromatic mutants of Phe484 eliminated all reactivities toward furanocoumarins. All single and double aliphatic mutants of Phe116, His117 and Phe484 and aromatic mutants of His117 generated carbon monoxide (CO) difference spectra with maxima at 420 nm (P420) indicative of incorrectly configured monooxygenases. These studies define residues Phe116, His117 and Phe484 as determinants of this insect P450's catalytic site integrity and residues Phe116 and Phe484 as determinants of its substrate specificity. Conservation of Phe116 and His117 in an array of lepidopteran CYP6B proteins implies that these amino acids serve a similar function in other monooxygenases of the insect CYP6B subfamily.


Posterior left thoracic cardiac sympathectomy by surgical division of the sympathetic chain: an alternative approach to treatment of the long QT syndrome.
Although high thoracic left sympathectomy via an anterior surgical approach is a highly efficacious treatment for refractory ventricular arrhythmias in patients with the long QT syndrome, the degree of sympathetic denervation has been variable, success of the operation is influenced by anatomical differences between patients, and Horner's syndrome may result. We hypothesized that interruption of sympathetic input to the heart could be accomplished using a posterior thoracic approach to this variable and often complex anatomy by division of the sympathetic chain rather than by direct destruction of the stellate and superior thoracic ganglia with the more conventional anterior, supraclavicular approach. In addition, the posterior approach should decrease the risk of Horner's syndrome by avoiding the ocular sympathetic efferent nerves. This posterior approach is described in five patients with the long QT syndrome and recurrent ventricular arrhythmias. After a mean follow-up of 18 +/- 12 months, all are alive without Horner's syndrome.


Effect of treatment success and empathy on surgeon attributions for back surgery outcomes.
This study examined the effect of conservative and surgical treatment success/failure on attributions by surgeons for low back surgical outcomes. It also examined empathy as a moderator of these attributions. Forty surgeons attributed surgical outcome in a hypothetical patient to physical and psychological factors. Results indicated that surgeons were less likely to attribute the cause of surgical failure to physical factors when the patient had already failed conservative treatment for low back pain. Surgeons also were more likely to attribute failed surgery, relative to successful surgery, to patient psychological factors. An interaction effect indicated that the latter difference was significant only when the patient had previously succeeded at conservative treatment. Empathy moderated this effect: empathic surgeons were less likely to see the failed surgery patient as psychologically culpable. This self-serving attributional style, as moderated by empathy, is discussed regarding its potential impact on patient care and physician judgment processes.


Antimicrobial susceptibility and mechanism of quinolone resistance in Campylobacter jejuni strains isolated from diarrheal patients in a hospital in Tokyo.
We determined the minimum inhibitory concentrations of six types of antimicrobial agents for 523 strains of Campylobacter jejuni that were isolated from diarrheal patients in a general hospital in Tokyo during the period between 2003 and 2005. It was revealed that 20.2%, 22.9%, 6.7%, and 0.6% of all the C. jejuni strains tested were resistant to ciprofloxacin (CPFX), nalidixic acid, ampicillin, and fosfomycin, respectively. All the strains were susceptible to clarithromycin and erythromycin. To elucidate the mechanism of quinolone resistance, in a total of 55 strains selected randomly, we carried out sequence determination and analysis of the quinolone-resistance determining regions (QRDRs) of their gyrA and gyrB genes. Amino-acid substitution at codon 86 (Thr --> IIe) of GyrA was found in all the 37 CPFX-resistant strains. There was no amino-acid substitution in the QRDR of the gyrB gene. All of the genomic DNAs of these 55 strains showed distinct pulsed-field gel electrophoresis patterns. Taken together, these results suggested that the quinolone resistance of C. jejuni was attributable mainly to the mutation at codon 86 (Thr --> IIe) in the QRDR of GyrA, and that this particular mutation and other silent mutations could be found not only in a certain clone of C. jejuni but also universally in a wide variety of strains.


Preparation and characterization of cellulose nanocrystal extracted from ramie fibers by sulfuric acid hydrolysis.
Cellulose nanocrystals (CNCs) were isolated from ramie fibers through chemical pretreatments accompanied by sulfuric acid hydrolysis. The influences of both temperature and hydrolysis time on the properties of CNCs were discussed in the present study. The characterization of CNCs was conducted using FT-IR, XRD, TEM, and TGA. The results showed the characteristics of obtained CNCs were influenced significantly by both temperature and time of hydrolysis. The crystallinity, dimensions, and thermal stability of CNCs were found to reduce by increasing both temperature and reaction time of hydrolysis. The optimal hydrolysis parameters were achieved at 45 °C for 30 min with 58% sulfuric acid to produce CNCs, rod-like particles with a high crystallinity (90.77%), diameter (6.67 nm), length (145.61 nm), and best thermal stability among all CNCs. The obtained CNCs had a higher potential for application of alternative reinforcing fillers in the nanocomposites.


Inducement and reversal of tetracycline resistance in Escherichia coli K-12 and expression of proton gradient-dependent multidrug efflux pump genes.
Expression of eight transporter genes of Escherichia coli K-12 and its DeltaacrAB mutant prior to and after induction of both strains to tetracycline resistance and after reversal of induced resistance were analyzed by quantitative reverse transcriptase PCR. All transporter genes were overexpressed after induced resistance with acrF being 80-fold more expressed in the DeltaacrAB tetracycline-induced strain.


High-throughput assays probing protein-RNA interactions of eukaryotic translation initiation factors.
Protein-RNA interactions are involved in all facets of RNA biology. The identification of small molecules that selectively block such bimolecular interactions could provide insight into previously unexplored steps of gene regulation. Such is the case for regulation of eukaryotic protein synthesis where interactions between messenger RNA (mRNA) and several eukaryotic initiation factors govern the recruitment of 40S ribosomes (and associated factors) to mRNA templates during the initiation phase. We have designed simple fluorescence polarization-based high-throughput screening assays that query the binding of several translation factors to RNA and found that the mixed inhibitor p-chloromercuribenzoate interferes with poly(A) binding protein-RNA interaction.


Divergent Asymmetric Synthesis of Panowamycins, TM-135, and Veramycin F Using C-H Insertion with Donor/Donor Carbenes.
Panowamycins are a group of isochroman-based natural products first isolated from Streptomyces sp. K07-0010 in 2012 by Satoshi Ōmura and co-workers that exhibit modest anti-trypanosomal activity. Herein we demonstrate the first syntheses of these natural products and their epimers. Stereoselective dirhodium-catalyzed C-H insertion reactions with a donor/donor carbene construct the substituted isochroman core in the key bond-forming step. The syntheses are completed without the use of protecting groups and feature a late-stage Wacker oxidation. Incongruent NMR spectra between natural and synthetic samples revealed the structural misassignment of panowamycin A and veramycin F. Computational NMR studies suggested panowamycin A to be an alternate diastereomer, which was confirmed by synthesizing this isomer. Concurrent with this work, in 2021 Mahmud and co-workers came to the same conclusion with an updated NMR analysis of panowamycin A. In a divergent, asymmetric sequence, we report the synthesis of panowamycin A, panowamycin B, TM-135, and veramycin F.


Radiation therapy oncology group protocol 02-29: a phase II trial of neoadjuvant therapy with concurrent chemotherapy and full-dose radiation therapy followed by surgical resection and consolidative therapy for locally advanced non-small cell carcinoma of the lung.
To evaluate mediastinal nodal clearance (MNC) rates after induction chemotherapy and concurrent, full-dose radiation therapy (RT) in a phase II trimodality trial (Radiation Therapy Oncology Group protocol 0229). Patients (n=57) with stage III non-small cell lung cancer (pathologically proven N2 or N3) were eligible. Induction chemotherapy consisted of weekly carboplatin (AUC = 2.0) and paclitaxel 50 mg/m(2). Concurrent RT was prescribed, with 50.4 Gy to the mediastinum and primary tumor and a boost of 10.8 Gy to all gross disease. The mediastinum was pathologically reassessed after completion of chemoradiation. The primary endpoint of the study was MNC, with secondary endpoints of 2-year overall survival and postoperative morbidity/mortality. The grade 3/4 toxicities included hematologic 35%, gastrointestinal 14%, and pulmonary 23%. Forty-three patients (75%) were evaluable for the primary endpoint. Twenty-seven patients achieved the primary endpoint of MNC (63%). Thirty-seven patients underwent resection. There was a 14% incidence of grade 3 postoperative pulmonary complications and 1 30-day, postoperative grade 5 toxicity (3%). With a median follow-up of 24 months for all patients, the 2-year overall survival rate was 54%, and the 2-year progression-free survival rate was 33%. The 2-year overall survival rate was 75% for those who achieved nodal clearance, 52% for those with residual nodal disease, and 23% for those who were not evaluable for the primary endpoint (P=.0002). This multi-institutional trial confirms the ability of neoadjuvant concurrent chemoradiation with full-dose RT to sterilize known mediastinal nodal disease.


Use of magnetic nanoparticles to manipulate the metabolic environment of bacteria for controlled biopolymer synthesis.
Magnetic nanoparticles (MNPs) were covalently immobilized on the surface of Acetobacter xylinus and the location of the bacteria was controlled to manipulate bacterial bioactivation. The bacteria were positioned in the middle of an incubation tube by applying an external magnetic field, and the cellulose produced at the different metabolizing locations was characterized by X-ray diffraction, electron microscopy, and differential scanning calorimetry. To the best of our knowledge, this is the first experiment in which MNPs were employed in the control of cell metabolism.


Rapid and progressive pulmonary fibrosis in 2 families with DNA repair deficiencies of undetermined etiology.
Known genetic causes of pediatric interstitial lung disease include disorders of surfactant metabolism, telomerase, and DNA repair. We report 4 children from 2 families with rapidly progressive and fatal pulmonary fibrosis. A novel DNA repair defect unrelated to the ataxia-telangiectasia mutated gene was found in 1 child from each family.


In vitro micropropagation of Dracaena sanderiana Sander ex Mast: An important indoor ornamental plant.
A protocol has been developed for in vitro plant regeneration from a nodal explant of Dracaena sanderiana Sander ex Mast. Nodal explant showed high callus induction potentiality on MS medium supplemented with 6.78 μM 2,4-dichlorophenoxyacetic acid (2,4-D) followed by 46.5 μM chlorophenoxy acetic acid (CPA). The highest frequency of shoot regeneration (85%) and number of shoots per explant (5.6) were obtained on medium supplemented with 7.84 μM N(6)-benzylaminopurine (BA). Rooting was high on MS solid compared to liquid medium when added with 7.38 μM indole-3-butyric acid (IBA). Fifty percent of the roots were also directly rooted as microcuttings on soil rite, sand and peat mixture (1:1:1). In vitro and ex vitro raised plantlets were used for acclimatization. More than 90% of the plantlets was successfully acclimatized and established in plastic pots. Ex vitro transferred plantlets were normal without any phenotypic aberrations.


Nucleotides in neuroregeneration and neuroprotection.
Brain injury generates the release of a multitude of factors including extracellular nucleotides, which exhibit bi-functional properties and contribute to both detrimental actions in the acute phase and also protective and reparative actions in the later recovery phase to allow neuroregeneration. A promising strategy toward restoration of neuronal function is based on activation of endogenous adult neural stem/progenitor cells. The implication of purinergic signaling in stem cell biology, including regulation of proliferation, differentiation, and cell death has become evident in the last decade. In this regard, current strategies of acute transplantation of ependymal stem/progenitor cells after spinal cord injury restore altered expression of P2X4 and P2X7 receptors and improve functional locomotor recovery. The expression of both receptors is transcriptionally regulated by Sp1 factor, which plays a key role in the startup of the transcription machinery to induce regeneration-associated genes expression. Finally, general signaling pathways triggered by nucleotide receptors in neuronal populations converge on several intracellular kinases, such as PI3K/Akt, GSK3 and ERK1,2, as well as the Nrf-2/heme oxigenase-1 axis, which specifically link them to neuroprotection. In this regard, regulation of dual specificity protein phosphatases can become novel mechanism of actions for nucleotide receptors that associate them to cell homeostasis regulation. This article is part of the Special Issue entitled 'Purines in Neurodegeneration and Neuroregeneration'.


On-line tracking of the coating of nanoscaled silica with titania nanoparticles via zeta-potential measurements.
Nanoscaled spherical silica particles were directly coated with the titania nanoparticles by means of a heterogenic coagulation. Silica was prepared by the Stöber method, titania by a hydrolysis-condensation reaction of tetrapropylorthotitanate under acidic conditions. The on-line tracking of the coating process was performed by measuring the change in zeta potential during the gradual addition of a titania sol to the spherical silica particles. Silica particles of various sizes were used to determine the consumption of the titania sol in the dependence upon the particle size. The coated and uncoated particles were characterized by zeta-potential measurements, acoustic attenuation spectroscopy, dynamic light scattering, and scanning electron microscopy.


Electrostatic evaluation of isosteric analogues.
A method is presented for enumerating a large number of isosteric analogues of a ligand from a known protein-ligand complex structure and then rapidly calculating an estimate of their binding energies. This approach takes full advantage of the observed crystal structure, by reusing the atomic co-ordinates determined experimentally for one ligand, to approximate those of similar compounds that have approximately the same shape. By assuming that compounds with similar shapes adopt similar binding poses, and that entropic and protein flexibility effects are approximately constant across such an isosteric series ("the frozen ligand approximation"), it is possible to order their binding affinities relatively accurately. Additionally, the constraint that the atomic coordinates are invariant allows for a dramatic simplification in the Poisson-Boltzmann method used to calculation the electrostatic component of the binding energy. This algorithmic improvement allows for the calculation of tens of thousands of binding energies per second for drug-like molecules, enabling this technique to be used in screening large virtual libraries of isosteric analogues. Most significantly, this procedure is shown to be able to reproduce SAR effects of subtle medicinal chemistry substitutions. Finally, this paper reports the results of the proposed methodology on seven model systems; dihydrofolate reductase, Lck kinase, ribosome inactivating protein, L: -arabinose binding protein, neuraminidase, HIV-1 reverse transcriptase and COX-2.


Effect of glucocorticoids on the development of COVID-19-associated pulmonary aspergillosis: A meta-analysis of 21 studies and 5174 patients.
COVID-19-associated pulmonary aspergillosis (CAPA) remains a high mortality mycotic infection throughout the pandemic, and glucocorticoids (GC) may be its root cause. Our aim was to evaluate the effect of systemic GC treatment on the development of CAPA. We systematically searched the PubMed, Google Scholar, Scopus and Embase databases to collect eligible studies published until 31 December 2022. The pooled outcome of CAPA development was calculated as the log odds ratio (LOR) with 95% confidence intervals (CI) using a random effect model. A total of 21 studies with 5174 patients were included. Of these, 20 studies with 4675 patients consisting of 2565 treated with GC but without other immunomodulators (GC group) and 2110 treated without GC or other immunomodulators (controls) were analysed. The pooled LOR of CAPA development was higher for the GC group than for the controls (0.54; 95% CI: 0.22, 0.86; p < .01). In the subgroups, the pooled LOR was higher for high-dose GC (0.90; 95% CI: 0.17, 1.62: p = .01) and dexamethasone (0.71; 95% CI: 0.35, 1.07; p < .01) but had no significant difference for low-dose GC (0.41; 95% CI: -0.07, 0.89; p = .09), and non-dexamethasone GC (0.21; 95% CI: -0.36, 0.79; p = .47), treated patients versus controls. GC treatment increases the risk of CAPA development, and this risk is particularly associated with the use of high-dose GC or dexamethasone treatment.


Detection of Bartonella henselae in the blood of 2 adult horses.
Bartonella spp. are emerging zoonotic agents that have been found in a wide variety of domestic animals and wildlife and cause a number of clinical syndromes. Bartonella sp. infection has been identified in a growing number of animal species, including cats, rodents, porpoises, and canids, but has not been reported in horses. To document the presence of Bartonella sp. in the blood of horses. One horse with chronic arthropathy and 1 horse with presumptive vasculitis. Blood samples were tested for the presence of Bartonella sp. by a combination of multiplex real-time polymerase chain reaction and enrichment culture technique. Bartonella henselae was isolated or detected in the blood of both horses. Bartonella henselae infection should be investigated as the cause of disease in horses.


Fictitious epilepsy in Munchausen syndrome by proxy: family psychodynamics.
This paper presents experience of Munchausen Syndrome by Proxy in four families where symptoms and signs of seizures in children were deliberately fabricated or induced by their own parent. At the time when the condition was suspected, the children (5, 7, 13 and 14 years old) had already been exposed to numerous investigations and antiepileptic drug intake-in one case resulting in drug intoxication. The important data, giving clues about how to uncover the condition, are peculiar to each family. After the condition was confirmed, a multidisciplinary team organized an approach aimed at protecting the abused child and changing the pathological parent-child relationship. Personality disorders were recognized in all illness perpetrators (the father in one and the mother in three families) and various psychopathological manifestations were present in all of the abused children. Psychodynamic factors causing the Manchausen Syndrome by Proxy are described and discussed.


Highly sensitive multiplexed DNA detection using multi-walled carbon nanotube-based multicolor nanobeacon.
A highly sensitive and selective multi-walled carbon nanotube (MWCNT)-based multicolor fluorescent nanobeacon is developed for multiplexed analysis of DNA in homogeneous solution. In this work, three different dye-labeled DNA hairpins were adsorbed on MWCNTs surface via π-stacking, which brings the dyes and MWCNTs into close proximity and leads to the quenching of fluorescence of the dyes. When target DNAs were added to the solution, the target DNAs specifically hybridize with the probes to form stable DNA duplexes, which weakens the interactions between the probes and MWCNTs, and results in the fluorescence recovery of the dyes. By using three 15-mer DNA fragments as proof-of-principle analytes, the proposed method showed good analytical performance. The limits of detection obtained were in the range of 35-42 pM. Moreover, this method also exhibits an excellent ability to discriminate between single nucleotide polymorphisms.


Biogenic and Risk Elements in Wines from the Slovak Market with the Estimation of Consumer Exposure.
Wine consumption delivers macroelements and microelements necessary for the proper metabolism. On the other hand, wine can be an important source of toxic metals. The aim of this study was to estimate the concentrations of Ca, Cd, Cu, Fe, Hg, Mg, Ni, Pb, and Zn in the Slovak and non-Slovak wines. The concentration of metals was evaluated with respect to the type, the alcohol content, and the age of Slovak wine. The general scheme of concentrations found was as follows Ca > Mg > Fe > Zn > Pb > Cd > Ni > Cu > Hg. The type of wine and the alcohol content do not have a significant impact on metal concentrations. Also, the age of wine has no influence on the mean concentration of metals, except for Zn. Metal concentrations in Slovak and non-Slovak wines indicate similar contents of metals, except for Ni. The contribution to both dietary reference values (DRVs) and provisional tolerable weekly intake (PTWI) evaluations in the Slovak wine suggested low dietary exposure to Ca, Cu, Fe, Mg, Ni, Zn, Cd, Hg, and Pb, respectively. However, we do not suggest that the consumption of all Slovak wines is healthy. The maximum Pb concentrations in Slovak wines exceed the maximum permitted level proposed by the European Commission. This might be proved by the results of the margin of the exposure (MOE) value evaluation in the samples containing the maximum Pb concentrations, showing a high risk of CKD and SBP in high and extreme consumption groups.


PCL/gelatin nanofibers embedded with doxorubicin-loaded mesoporous silica nanoparticles/silver nanoparticles as an antibacterial and anti-melanoma cancer.
Melanoma cancer wound healing is critical and complex and poses a significant challenge to researchers. Drug resistance, adverse side effects, and inefficient localization of chemotherapeutic drugs limit common treatment strategies in melanoma cancer. Using drug delivery nanostructures with low side effects and high efficiency, besides having antibacterial and antiseptic properties, can effectively repair the damage caused by the disease. To this end, this study aimed to develop a drug delivery nanosystem based on doxorubicin (DOX)-loaded amine-functionalized mesoporous silica nanoparticles (MSNs), linked with green synthesized silver nanoparticles (AgNPs). Characterization methods including microscopic methods and X-ray diffraction (XRD) confirmed the synthesis and functionalization of the well-dispersed nanoparticles with nanosized and uniform structures. The poly(ε-caprolactone) (PCL) nanofibers as a strong scaffold were produced by the blow spinning method and DOX-loaded nanoparticles were blow spun on PCL nanofibers along with gelatin solution. The resulting nanosystem including nanofibers and nanoparticles (NFs/NPS) showed a fine loading percent with a proper release profile of DOX and AgNPs and low hemolysis activity. Moreover, besides preventing infection by AgNPs, the DOX-loaded NFs/NPs could effectively destroy melanoma cancer cells. The attachment of normal cells to the nanoparticles-loaded nanofibers scaffold revealed the possibility of healing wounds caused by melanoma cancer.


Oxidation and electrical properties of chromium-iron alloys in a corrosive molten electrolyte environment.
Chromium-iron (CrFe) binary alloys have recently been proposed to serve as the "inert" anode for molten oxide electrolysis (MOE). Herein, the effects of anodic polarization on physical and functional properties of CrFe anodes in the corrosive environment of MOE are studied via empirical observations and theoretical calculations. The findings indicate that the alloys form an inner chromia-alumina solid-solution covered by an MgCr2O4 spinel layer. A survey into the electrical properties of the detected oxides suggests that the layered oxide scale function as an efficient conductor of electricity at elevated temperature. The formation mechanism of the oxides is also investigated.


Auditory brainstem responses (ABR) in neonates with hyperbilirubinemia.
The technique of ABR testing was applied to 25 infants with neonatal hyperbilirubinemia at levels exceeding that for exchange transfusion, in an attempt to study potential influence of bilirubin toxicity on the auditory brainstem pathway. The test was performed at a mean conceptional age of 40.4 +/- 0.6 weeks just after discharge. Twenty normal term neonates of comparable birth weights and conceptional ages, who had no hyperbilirubinemia, were also examined for comparison. Fifty six percent (n = 14) of the hyperbilirubinemic neonates had some abnormality in the ABR pattern, the major one being a transient increase in the threshold of wave V (7, fail-30; 5, fail-45). Wave V, however, was consistently present at 30 dBnHL click stimulus in all the normal neonates (pass-30; normal threshold). Further, mean ABR latencies (wave III, V) and 1-V interpeak latency (brainstem conduction time) were significantly prolonged in jaundiced neonates as compared with controls (P less than 0.01). ABR changes were strongly correlated with the serum bilirubin levels (P less than 0.001). On follow up retesting at 3 months, however, all infants were found to have normal ABR latencies and threshold. Neonatal jaundice was associated with significant transient aberrations of ABR, suggestive of a transient toxic brainstem encephalopathy.


Surface ECG criteria can discriminate post-septal pacing cardiac memory from ischemic T wave inversions.
Cardiac memory (CM) refers to transient T wave changes that appear after cessation of a period of abnormal ventricular activation, such as right ventricular (RV) pacing. ECG criteria for differentiating post-pacing CM from ischemia-induced T wave changes were previously published only for apical, but not for septal RV pacing. To find ECG criteria for discriminating post-septal pacing CM from ischemic T wave inversions. ECGs were analyzed in 2 groups: CM (n = 23) and ischemia (n = 26). CM was induced by 2 weeks of DDD pacing with a short AV delay. Ischemic patients were grouped by culprit vessel: left anterior descending (LAD), circumflex (Cx), right coronary artery (RCA). CM was visible on the ECG after 1 week of ventricular pacing, started to disappear in <1 week after pacing cessation and was completely reversible within 4 weeks of pacing cessation. T wave axis differed between CM (75.8 ± 18.5°) and Cx (-25.2 ± 25.5°, p < 0.01) and RCA (-18.3 ± 18.9°, p < 0.01) groups, but not compared to LAD group (96.4 ± 65.0°, p = 0.17). The combination of (1) positive T wave in aVF; and (2) (i) T wave amplitude in aVF ≥ the absolute value of the most negative precordial T wave, or (ii) positive T wave in V5 and positive or isoelectric T wave in lead I identified CM from all ischemia with a sensitivity of 91% and a specificity of 92%. ECG criteria can discriminate post-septal RV pacing CM from ischemic changes with high sensitivity and specificity.


The significance of ultraviolet radiation for eye diseases. A review with comments on the efficacy of UV-blocking contact lenses.
Acute and cumulative ultraviolet radiation (UVR) exposure has been proposed as an important causative factor in the development of a whole spectrum of eye diseases. The present review examines the scientific evidence for and against such an association, with special emphasis on recent additions to the literature. The sun is the main UVR source on earth, and it is beyond scientific doubt that the cornea can be harmed by both acute and cumulative ambient exposures. There is also powerful epidemiological support for an association between chronic UVR exposure and the formation of cataracts and pterygia. The evidence in support of UVR linkage to pinguecula, ocular neoplasms and retinal changes is weaker--in part because there are fewer studies reported in the literature. It is concluded that UVR-blocking hydrogel contact lenses and spectacles are two equally effective preventive measures in minimizing unnecessary suffering and health costs, especially for people who spend a significant time outdoors and for those who live in more UV intense environments. UVR-blocking contact lenses and spectacles must not, however, be substitutes in situations that require UVR-blocking safety goggles.


[Electrosurgical concepts in ENT medicine. History, fundamentals and practice].
The beneficial use of heat in the context of medical treatments was documented even in ancient times. The development of high-frequency alternating current generators led to actual electrosurgery, in which primary heating of the tissue takes place. In day-to-day clinical practice electrosurgery is used for coagulation and for electrotomies. There are both unipolar and bipolar techniques for these procedures. When a unipolar technique is used the active electrode is in the tip of the instrument and the patient plate is usually affixed to the patient's skin at a site outside the operating field. The bipolar technique differs in that there are no electrodes that need to be attached externally; both poles are contained inside the operating instrument, e.g. in the two prongs of a forceps. In radiofrequency surgery high-frequency electrical energy is applied directly into the tissue by a unipolar or bipolar technique. In this way it is possible to cause interstitial tissue lesions while sparing the superficial mucous membranes.


[Changes in the activity and conditioned-reflex behavior of white rats during and after chronic microwave irradiation].
Albino rats were exposed to chronic (1-3 months) electromagnetic radiation (2375 MHz; 1, 5, 10, 50 and 500 microW/cm2; 7 hours a day). Inhibition of the activity during the open field tests and diminution of consolidation of the defence conditioned reflexes in a shuttle chamber occurred during exposure (5 to 500 microW/cm2) while the activity increased and reflexes consolidation gradually normalized during the post-irradiation period.


Efficacy and safety of dose-dense paclitaxel plus carboplatin as neoadjuvant chemotherapy for advanced ovarian, fallopian tube or peritoneal cancer.
Interval debulking surgery (IDS) after neoadjuvant chemotherapy (NAC) is currently one of the preferred treatment options for advanced ovarian, fallopian tube or peritoneal cancer. This study was conducted to evaluate the clinical efficacy and safety of dose-dense paclitaxel plus carboplatin therapy (ddTC therapy) as NAC for these cancers. A retrospective study was conducted in 25 patients with Stage III/IV ovarian, fallopian tube or peritoneal cancer who received ddTC therapy as NAC. For ddTC therapy, paclitaxel (80 mg/m2) was administered intravenously on Days 1, 8 and 15 and carboplatin (AUC 6.0 mg/ml × min) was administered intravenously on Day 1 every 3 weeks. IDS was performed after three cycles of ddTC therapy, and ddTC therapy was also continued after surgery. With ddTC therapy as NAC, the response rate was 92% and disease progression did not occur in any patient. Grade 4 hematologic toxicity and ≥Grade 3 non-hematologic toxicity both occurred in 8% of the patients, but no patient discontinued NAC because of adverse events. When IDS was performed, the complete surgery rate was 64% and the optimal surgery rate was 96%. ≥Grade 3 perioperative complications occurred in 16% of the patients, but there were no perioperative deaths. Median overall survival was 35.7 months and median progression-free survival was 17.7 months. This study showed that ddTC therapy was considerably effective and tolerable as NAC. The complete surgery rate was high with IDS, and perioperative complications were acceptable.


Proposal to decrease incidence, morbidity, and associated healthcare costs regarding difficult and traumatic urethral catheterization - a protocol for DMC hospitals: A pilot study.
Difficult and traumatic urethral catheterization is a common reason for urologic consult. Catheter insertion and management is common for patients who are managed in the hospital setting. A four-question survey was distributed across three hospitals at a single-institution. A total of 41 nursing staff responses were recorded. Forty-four percent of the nursing staff reported prior participation in a traumatic catheter insertion. Ninety percent of total responders reported a prior involvement with a difficulty catheter. Patient morbidity and healthcare costs regarding traumatic and difficult catheterization is significant. Utility of protocols and education could potentially reduce these burdens and enhance patient care.


Completeness and registration bias in PROCARE, a Belgian multidisciplinary project on cancer of the rectum with participation on a voluntary basis.
PROCARE, a Belgian multidisciplinary project on rectal cancer, started in 2006 with participation on a voluntary basis. Completeness and bias of registration in PROCARE were assessed. Data from 6353 patients with rectal cancer were extracted from the population based Belgian Cancer Registry for the period 2006-2008. Registration bias was studied by comparing patient, tumour and treatment characteristics of cases registered and non-registered in PROCARE. Relative survival (RS) of patient subgroups was analysed. PROCARE included 37% of all Belgian rectal cancer patients. Registration was highly variable between participating centres which recorded on average 56% of their patients. Significant differences in patient, tumour and treatment related characteristics were observed between registered and non-registered patients. The 5-year RS was 77% (95% confidence interval (CI): 74-80%) for registered patients and 56% (95% CI: 53-59%) for non-registered patients. After adjustment for patient, tumour characteristics and volume of centre, the relative excess risk of dying (RER) between registered and non-registered patients was 2.15 (95% CI: 1.85-2.50, p<0.001). The 5-year RS of patients treated in centres that never participated in the project was 59% (95% CI: 55-63%) and, after adjustment, the RER was 1.16 (95% CI: 1.00-1.35, p<0.050) compared to patients of the participating centres. Registration of PROCARE patient data was incomplete, biased and variable between centres. Participation on a voluntary basis should be avoided for further projects. Quality assurance on a centre level requires compulsory and complete registration with a minimal but relevant data set for all patients treated in all centres.


Practicing more retrieval routes leads to greater memory retention.
A wealth of research has shown that retrieval practice plays a significant role in improving memory retention. The current study focused on one simple yet rarely examined question: would repeated retrieval using two different retrieval routes or using the same retrieval route twice lead to greater long-term memory retention? Participants elaborately learned 22 Japanese-Chinese translation word pairs using two different mediators. Half an hour after the initial study phase, the participants completed two retrieval sessions using either one mediator (Tm1Tm1) or two different mediators (Tm1Tm2). On the final test, which was performed 1week after the retrieval practice phase, the participants received only the cue with a request to report the mediator (M1 or M2) followed by the target (Experiment 1) or only the mediator (M1 or M2) with a request to report the target (Experiment 2). The results of Experiment 1 indicated that the participants who practiced under the Tm1Tm2 condition exhibited greater target retention than those who practiced under the Tm1Tm1 condition. This difference in performance was due to the significant disadvantage in mediator retrieval and decoding of the unpracticed mediator under the Tm1Tm1 condition. Although mediators were provided to participants on the final test in Experiment 2, decoding of the unpracticed mediators remained less effective than decoding of the practiced mediators. We conclude that practicing multiple retrieval routes leads to greater memory retention than focusing on a single retrieval route. Thus, increasing retrieval variability during repeated retrieval practice indeed significantly improves long-term retention in a delay test.


Effectiveness of Genotype-Specific Tricyclic Antidepressant Dosing in Patients With Major Depressive Disorder: A Randomized Clinical Trial.
Evidence of the clinical benefit of pharmacogenetics-informed treatment (PIT) with antidepressants is still limited. Especially for tricyclic antidepressants (TCAs), pharmacogenetics may be of interest because therapeutic plasma concentrations are well defined, identification of optimal dosing can be time consuming, and treatment is frequently accompanied by adverse effects. To determine whether PIT results in faster attainment of therapeutic TCA plasma concentrations compared with usual treatment in patients with unipolar major depressive disorder (MDD). This randomized clinical trial compared PIT with usual treatment among 111 patients at 4 centers in the Netherlands. Patients were treated with the TCAs nortriptyline, clomipramine, or imipramine, with clinical follow-up of 7 weeks. Patients were enrolled from June 1, 2018, to January 1, 2022. At inclusion, patients had unipolar nonpsychotic MDD (with a score of ≥19 on the 17-item Hamilton Rating Scale for Depression [HAMD-17]), were aged 18 to 65 years, and were eligible for TCA treatment. Main exclusion criteria were a bipolar or psychotic disorder, substance use disorder, pregnancy, interacting comedications, and concurrent use of psychotropic medications. In the PIT group, the initial TCA dosage was based on CYP2D6 and CYP2C19 genotypes. The control group received usual treatment, which comprised the standard initial TCA dosage. The primary outcome was days until attainment of a therapeutic TCA plasma concentration. Secondary outcomes were severity of depressive symptoms (measured by HAMD-17 scores) and frequency and severity of adverse effects (measured by Frequency, Intensity, and Burden of Side Effects Rating scores). Of 125 patients randomized, 111 (mean [SD] age, 41.7 [13.3] years; 69 [62.2%] female) were included in the analysis; of those, 56 were in the PIT group and 55 were in the control group. The PIT group reached therapeutic concentrations faster than the control group (mean [SD], 17.3 [11.2] vs 22.0 [10.2] days; Kaplan-Meier χ21 = 4.30; P = .04). No significant difference in reduction of depressive symptoms was observed. Linear mixed-model analyses showed that the interaction between group and time differed for the frequency (F6,125 = 4.03; P = .001), severity (F6,114 = 3.10; P = .008), and burden (F6,112 = 2.56; P = .02) of adverse effects, suggesting that adverse effects decreased relatively more for those receiving PIT. In this randomized clinical trial, PIT resulted in faster attainment of therapeutic TCA concentrations, with potentially fewer and less severe adverse effects. No effect on depressive symptoms was observed. These findings indicate that pharmacogenetics-informed dosing of TCAs can be safely applied and may be useful in personalizing treatment for patients with MDD. ClinicalTrials.gov Identifier: NCT03548675.


Current status of emergency residency training programs in Turkey: after 14 years of experience.
Emergency residency training programs, which have been developing in Turkey over the last 14 years, have been improving emergency health services by training each year a significant number of emergency medicine specialists. Sufficient data about these emergency residency training programs is not currently available. The purpose of this study is to determine (i) the structure of emergency residency training programs and (ii) trainer and resident views concerning these programs. The data in this cross-sectional study was gathered by means of questionnaires. Three different forms of questionnaires were used for residents, trainers, and heads of departments. This study covers 20 emergency medicine departments and 261 physicians. It was determined that written rotational objectives have been indicated in 17 of the emergency medicine departments and log books are used in 16 departments. Although 60% of resident views on 'practical skills', 23% on 'the contribution of rotations to the training', and 44% on 'the level of residency training programs' were rated as 'sufficient', trainers indicated 'sufficiency' on these subjects as 78, 37, and 77%, respectively. Regarding theoretical and practical skills, residents and trainers, respectively rated as 'sufficient' following subjects: cardiovascular 74, 91%; neurology 68, 86%; resuscitation 83, 98%; trauma 76, 87%; orthopedics 56, 75%; pediatrics 16, 27%; and toxicology 63, 82%. Most of the departments have developed the basic components for resident education. Residents and trainers frequently had different views on their own level of knowledge, practical skills, and the content of their training.


MRI-detectability and histological factors of prostate cancer including intraductal carcinoma and cribriform pattern.
Histopathological characteristics affecting the detectability of clinically significant prostate cancer (csPCa) on magnetic resonance imaging (MRI) remain unclear. This study aimed to compare the histopathology between MRI-detectable and MRI-undetectable cancers, emphasizing intraductal carcinoma of the prostate (IDC-P) and predominant Gleason pattern 4 subtype. This single-center retrospective study enrolled 153 consecutive patients with 191 lesions who underwent preoperative multiparametric MRI and subsequent radical prostatectomy. MRI/histopathological findings and area fractions of histological components (cancer cells, stroma, and luminal spaces) of MRI-detectable and MRI-undetectable cancers were compared. Data were analyzed using Fisher's exact, independent t, or Mann-Whitney U tests. Overall, 148 (77%) and 43 (23%) cancers were MRI-detectable and MRI-undetectable, respectively. MRI-detectable cancers were significantly larger than MRI-undetectable cancers (p = 0.03). The percentage of lesions in Grade Group 3 or higher was significantly higher among MRI-detectable cancers than among MRI-undetectable cancers (p = 0.02). MRI detectability of csPCa was associated with increases in relative area fractions of cancer cells (p < 0.001) and decreases in those of stroma (p < 0.001) and luminal spaces (p < 0.001) in prostate cancer (PCa) than the percentage of Gleason pattern 4 (p = 0.09). The percentage of lesions containing IDC-P was similar for MRI-detectable and MRI-undetectable cancers (40% vs. 33%; p = 0.48). The distribution of cribriform gland subtypes was not significantly different between MRI-detectable and MRI-undetectable Gleason pattern 4 subtype cancers (p > 0.99). Contrarily, the ratio of fused gland subtype was significantly higher in MRI-detectable than in MRI-undetectable cancers (p = 0.03). Furthermore, the ratio of poorly-formed gland subtype was significantly higher in MRI-undetectable than in MRI-detectable cancers (p = 0.01). MRI detectability of csPCa is strongly associated with the relative area fractions of cancer cells, stroma, and luminal spaces in PCa rather than conventional histopathological parameters. Neither the presence nor the percentage of IDC-P affected MRI detectability.


The effect of expansive open-door laminoplasty on spinal canal diameter: an experimental study on rabbits.
The aim of this experimental study was to evaluate the effect of expansive open-door laminoplasty with simple suture fixation on spinal canal diameter in a rabbit model. Twenty white New Zealand rabbits were operated on with C4-C7 Hirabayashi open-door laminoplasty. The spinal canal diameter was evaluated radiologically on preoperative day 1 and postoperative days 1 and 42. The mean spinal canal diameter was 6.42 mm preoperatively, 8.04 mm on postoperative day 1 and 8.02 mm at day 42. There was a significant difference between the mean preoperative and postoperative day 1 spinal canal diameter (p<0.001). There was no significant difference between the mean spinal canal diameter at postoperative day 1 and 42 (p>0.05). Our results suggest that the open-door laminoplasty with simple suture fixation is an effective method to expand the spinal canal diameter. No recurrent narrowing is expected in short term.


Smoking and adipose tissue inflammation suppress leptin expression in Japanese obese males: potential mechanism of resistance to weight loss among Japanese obese smokers.
The effect of smoking on leptin regulation is controversial. Smoking may induce low-grade inflammation. Recent series of studies indicated the critical role of macrophage migration in the establishment of adipose tissue inflammation. In this study, we aimed to see the effects of smoking and inflammation on leptin regulation both at cellular and epidemiological levels. We compared the concentration of inflammatory markers and serum leptin levels among Japanese male subjects. Additionally, leptin and intercellular adhesion molecule (ICAM) -1 gene expression was assessed in adipocytes co-cultured with or without macrophages in the presence or absence of nicotine and/or lipopolysaccharide (LPS). In subjects with BMI below 25 kg/m2, both WBC counts and soluble-ICAM-1 levels are significantly higher in smokers than in non-smokers. However, leptin concentration did not differ according to smoking status. However, in subjects with BMI over 25 kg/m2, smokers exhibited significantly lower serum leptin level as well as higher WBC counts and s-ICAM-1 concentration as compared with non-smokers. Leptin gene expression was markedly suppressed in adipocytes co-cultured with macrophages than in adipocyte culture alone. Furthermore, nicotine further suppressed leptin gene expression. ICAM-1 gene expression was markedly up-regulated in adipocytes co-cultured with macrophages when stimulated with LPS. Adipose tissue inflammation appears to down-regulate leptin expression in adipose tissues. Nicotine further suppresses leptin expression. Thus, both smoking and inflammation may diminish leptin effect in obese subjects. Therefore, obese, but not normal weight, smokers might be more resistant to weight loss than non-smokers.


Interstitial distribution of charged macromolecules in the dog lung: a kinetic model.
A mathematic model was constructed to investigate conflicting physiologic data concerning the charge effect of continuous capillaries to macromolecules in the lung. We simulated the equilibration kinetics of lactate dehydrogenase (MR 4.2 nM) isozymes LDH 1 (pI = 5.0) and LDH 5 (pI = 7.9) between plasma and lymph using previously measured permeability coefficients, lung tissue distribution volumes (VA) and plasma concentrations (CP) in lung tissue. Our hypothesis is that the fixed anionic charges in interstitium, basement membrane, and cell surfaces determine equilibration rather than charged membrane effects at the capillary barrier, so the same capillary permeability coefficients were used for both isozymes. Capillary filtration rates and protein fluxes were calculated using conventional flux equations. Initial conditions at baseline and increased left atrial pressures (PLA) were those measured in animal studies. Simulated equilibration of isozymes over 30 h in the model at baseline capillary pressures accurately predicted the observed differences in lymph/plasma concentration ratios (CL/CP) between isotopes at 4 h and equilibration of these ratios at 24 h. Quantitative prediction of isozyme CL/CP ratios was also obtained at increased PLA. However, an additional cation selective compartment representing the surface glycocalyx was required to accurately simulate the initial higher transcapillary clearances of cationic LDH 5. Thus experimental data supporting the negative barrier, positive barrier, and no charge barrier hypotheses were accurately reproduced by the model using only the observed differences in interstitial partitioning of isozymes without differences in capillary selectivity.


Analysis of chemical warfare agents. I. Use of aliphatic thiols in the trace level determination of Lewisite compounds in complex matrices.
A series of normal aliphatic thiols have been used to derivatise the chemical warfare agents Lewisites I and II (LI and LII) in hydrocarbon matrices. Varying the chain length of the thiol allowed adjustment of derivative tR by 5.9 min for Lewisite I and 5.3 min for Lewisite II. Linear regression analysis of the chain length of the thiol derivatives of the Lewisite species, and that of a series of normal alkanes against tR, allowed regression models to be developed for each set of compounds. Application of the models allowed thiol reagents to be chosen to give derivatives of Lewisites I and II that eluted before and after the major hydrocarbon contaminant. Limits of detection were comparable for all thiol derivatives analysed by GC-MS in the selection ion monitoring mode (all below 1 microg ml(-1)). The robustness of this approach was illustrated by successful identification of Lewisite I in samples from the Sixth Proficiency Test (organised by the Organisation for the Prohibition of Chemical Weapons, OPCW) in a matrix of 1 mg ml(-1) diesel oil.


In vitro translation of cytosolic and peroxisomal epoxide hydrolase and catalase on liver polyribosomes from untreated and clofibrate-treated C57B1/6 mice.
Free and membrane-bound polyribosomes were isolated from the livers of untreated and clofibrate-treated male C57B1/6 mice. The in vitro translation products were investigated in a rabbit reticulocyte cell-free system by immunoprecipitation of cytosolic epoxide hydrolase, catalase and albumin. The soluble forms of epoxide hydrolase present in cytosol and in peroxisomes were found to be synthesized on free polyribosomes and could not be distinguished from each other, since only one primary translation product was found with the methods used. Clofibrate treatment was found to increase total protein synthesis, synthesis of soluble epoxide hydrolase and translational efficiency of the isolated polyribosomes.


Drug advertisements published in Indian Medical Journals: Are they ethical?
It is observed in studies done for western medical journals that insufficient information related to drug is usually provided in the drug advertisements published in them. As data for advertisements published in Indian Medical Journals were lacking, this study was designed with the aim of evaluating drug advertisements published in Indian Medical Journals for adequacy of information on drug and references given to support the claim made in the advertisements. Cross-sectional survey. All medical journals related to clinical practice subscribed by the Central Library of Government Medical College, Surat, (Indian Journal of Pediatrics [IJP], Indian Pediatrics [IP], Journal of the Association of Physicians of India [JAPI], Journal of Indian Medical Association [JIMA], Indian Journal of Critical Care Medicine [IJCCM], Indian Journal of Medical and Pediatric Oncology [IJMPO], Indian Journal of Gastroenterology [IJG], Indian Journal of Ophthalmology [IJO], and Journal of Obstetrics and Gynecology of India [JOGI] were evaluated for adequacy of reporting of various parameters in drug advertisements published in these journals on the basis of "World Heath Organization (WHO)" criteria. References mentioned to support claims were also evaluated. Descriptive statistics was used to describe data as frequencies, percentages, and 95% confidence interval around the percentage. Generic name was mentioned in 90% advertisements. Indications were mentioned in 84% advertisements. Dose, precautions, and contraindications were mentioned in 24%, 17%, and 16% advertisements, respectively. Adverse effects and postal address of pharmaceutical company was mentioned in 19% and 74% advertisements, respectively. Price was mentioned in only 5% advertisements. Only 28% claims were supported by references. Most common references were Journal articles (75%). Drug advertisements published in Indian Medical Journals are poor in reporting various parameters according to WHO criteria.


Evolution of the regionalization and patterning of the vertebrate telencephalon: what can we learn from cyclostomes?
The telencephalon, the most anterior part of the vertebrate central nervous system (CNS), is a highly diversified region of the vertebrate body. Its evolutionary origin remains elusive, especially with regard to the ancestral state of its architecture as well as the origin of telencephalon-specific neuron subtypes. Cyclostomes (lampreys and hagfish), the sister group of the gnathostomes (jawed vertebrates), serve as valuable models for studying the evolution of the vertebrate CNS. Here, we summarize recent studies on the development of the telencephalon in the lamprey. By comparing detailed developmental studies in mammals, we illustrate a possible ancestral developmental plan underlying the diversification of the vertebrate telencephalon and propose possible approaches for understanding the early evolution of the telencephalon.


Micelle to solvent stacking of organic cations in micellar electrokinetic chromatography with sodium dodecyl sulfate.
The on-line sample concentration technique, micelle to solvent stacking (MSS), was studied for small organic cations (quaternary ammonium herbicides, β-blocker drugs, and tricyclic antidepressant drugs) in reversed migration micellar electrokinetic chromatography. Electrokinetic chromatography was carried out in fused silica capillaries with a background solution of sodium dodecyl sulfate (SDS) in a low pH phosphate buffer. MSS was performed using anionic SDS micelles in the sample solution for analyte transport and methanol or acetonitrile as organic solvent in the background solution for analyte effective electrophoretic mobility reversal. The solvent also allowed for the separation of the analyte test mixtures. A model for focusing and separation was developed and the mobility reversal that involved micelle collapse was experimentally verified. The effect of analyte retention factor was observed by changing the % organic solvent in the background solution or the concentration of SDS in the sample matrix. With an injection length of 31.9 cm (77% of effective capillary length) for the 7 test drugs, the LODs (S/N=3) of 5-14 ng/mL were 101-346-fold better when compared to typical injection. The linearity (R(2), range=0.025-0.8 μg/mL), intraday and interday repeatability (%RSD, n=10) were ≥0.988, <6.0% and <8.5%, respectively. In addition, analysis of spiked urine samples after 10-fold dilution with the sample matrix yielded LODs=0.02-0.10 μg/mL. These LODs are comparable to published electrophoretic methods that required off-line sample concentration. However, the practicality of the technique for more complex samples will rely on dedicated sample preparation schemes.


Mindfulness-based cognitive therapy for Fear of Recurrence in Ovarian Cancer Survivors (FROCS): a single-arm, open-label, pilot study.
Fear of recurrence is common following treatment for cancer. Our aim was to assess the feasibility of mindfulness-based cognitive therapy (MBCT) to treat fear of cancer recurrence (FCR) in ovarian cancer survivors. Investigator initiated, single-arm, open-label, pilot study. Women were eligible after completing adjuvant treatment. The intervention was an 8-week MBCT course of weekly 2-h group sessions. The primary outcome was FCR measured by the FCR inventory. Secondary outcomes were depression and anxiety measured by the Hospital Anxiety and Depression Scale (HADS). The study is registered with the Australian and New Zealand Clinical Trials Registry ACTRN12615000213549. Between May 8, 2015, and May 6, 2019, 33 participants were enrolled. Ten women withdrew. Data were evaluable for 19 participants. There was a significant decrease in FCR at 8 weeks (FCR inventory mean 63.00, SD 27.90) compared to pre-intervention (FCR inventory mean 71.03, SD 31.01) but not at 6 months (FCR inventory mean 63.65, SD 30.08). No differences in depression were observed at baseline (HADS mean 3.42, SD 2.41), 8 weeks (HADS mean 3.10, SD 1.79) and 6 months (HADS mean 2.73, SD 1.88). Anxiety decreased from baseline (HADS mean 8.72, SD 3.99) at both 8 weeks (HADS mean 6.89, SD 2.98) and 6 months (HADS mean 7.06, SD 3.87). MBCT may be effective as a treatment for FCR and anxiety in women following diagnosis and treatment of ovarian cancer. A randomised controlled trial is required to assess the efficacy of MBCT for FCR but may not be feasible due to high rates of withdrawal.


Genetic differentiation between two host "races" and two species of cleptoparasitic bees and between their two hosts.
In this paper we test the following two hypotheses: (1) that apparently conspecific samples of the cleptoparasitic bee Coelioxys funeraria, differing markedly in size and reared from different host species, do indeed represent one panmictic population; (2) that bees that nest in holes in wood or twigs have higher levels of genetic variation than those nesting in the ground. Based upon 41 loci, the genetic differences between the two samples of C. funeraria could be explained entirely in terms of sampling error. In contrast, the sympatric C. moesta showed 16 fixed allelic differences from the C. funeraria samples. Similarly, the two hosts of C. funeraria, Megachile relativa and M. inermis, had 21 fixed allelic differences between them out of 42 presumptive gene loci. Heterozygosities among the wood-nesting bees were not particularly high for Hymenoptera, ranging from 0.045 to 0.054. Comparisons of heterozygosity estimates among bees remain ambiguous as to whether soil nesting confers sufficient environmental buffering effects to reduce possible advantages of heterosis in ground-nesting species.


The development of the referral outcome diagram and an analysis of laboratory cancer detection rates in the English NHS cervical screening programme--is there an optimum level of detection of CIN 1 and CIN 2 lesions?
To use routine annual data from the English cervical screening laboratories (KC61 returns) to evaluate individual laboratory return characteristics with particular reference to factors associated with sensitivity and specificity. A graphical technique has been developed using data on referral to colposcopy and histological outcomes called a referral outcome (ROUT) diagram. The average grade of cervical intraepithelial neoplasia (CIN) detected (the mean CIN score, MCS) is plotted against the odds of a false-positive referral. Further analysis has been conducted to examine the relationship between the MCS and screen-detected invasive cancer rate. There are large variations in ROUT diagram positions of individual laboratories and the diagram can be used to identify laboratories for further investigation. These variations are strongly influenced by substantial differences in the rate of low-grade referrals and the MCS (and positive predictive value) are inversely related to the referral rate for low-grade cytology (P < 0.001). There is a strong association between high MCS values and increased screen-detected cancer rates (P < 0.001) particularly above an MCS of 2.2. The data can be re-formulated in terms of CIN 2 and CIN 3 only where it can be shown that the invasive cancer rate rapidly increases if the numbers of CIN 2 lesions detected drops below 50% of the number of CIN 3 lesions. Given the complexity of cervical screening this may best be viewed as a hypothesis generating observation, best tested by interventional studies. The ROUT diagram represents a new and potentially interesting way of presenting annual return data. The national programme in England needs to balance the prevention of cancer against too many unnecessary referrals to colposcopy and the ROUT diagram, and associated data given in this paper may help toward this. Further research is required including examining the role of referral policy and threshold criteria in influencing low-grade referrals and the relationship between MCS and cancer detection rate.


Beriberi heart disease in a schizophrenic with an unusual diet.
A 37-year-old male presented with peripheral edema of sudden onset. Other signs of heart failure were absent. Subsequent evaluation revealed that the patient was a schizophrenic whose diet consisted almost entirely of carbohydrates. A clinical diagnosis of beriberi heart disease was made and the patient improved dramatically within several days of thiamine supplementation. The presentation of beriberi heart disease in developed countries is discussed. Emphasis is placed on food faddists and psychiatric patients in whom clinical findings may be subtle or absent.


Epidemiology and clinical presentation of respiratory syncytial virus infection in a rural area of southern Mozambique.
Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection (LRTI) in infants throughout most of the world, but little is known about RSV infection in Africa where LRTI are among the leading causes of infant and childhood death. The study took place in a rural district hospital in southern Mozambique between October, 1998, and May, 2000. From all children (n = 5635) <1 year of age presenting to an outpatient department with cough or nasal secretion and all children (n = 1307) <5 years of age admitted to hospital with a LRTI, a nasopharyngeal aspirate was collected and tested for RSV by enzyme-linked immunosorbent assay (Abbott). RSV infection was found in 8.6% of study infants in the outpatient department and 10.6% of admitted children with LRTI. Cases presented in predictable yearly outbreaks during the warm and rainy season. Lower respiratory tract involvement was frequent (59.7%). Cough, chest indrawing and increased respiratory rate were all independently related to RSV infection. Wheezing was infrequent. Bacterial coinfection (4.6%) and the case-fatality rate (3.4%) were low. There is a substantial burden of disease attributable to RSV infection in this rural African setting, with the highest incidence and severity occurring in young infants.


A hairy development in hypertrichosis: a brief review of Ambras syndrome.
Ambras syndrome was described less than 20 years ago. The initial report focused on the subtle, but important distinguishing characteristics that separate this from other forms of congenital hypertrichosis. This review, we examine this fascinating syndrome, and the current scientific perspectives in discussion. This review will help increase and expand our knowledge base of this uncommon syndrome, and should encourage future dermatologic analysis and reports on Ambras syndrome.


Different mechanisms of increased proteolysis in atrophy induced by denervation or unweighting of rat soleus muscle.
Mechanisms of accelerated proteolysis were compared in denervated and unweighted (by tail-cast suspension) soleus muscles. In vitro and in vivo proteolysis were more rapid and lysosomal latency was lower in denervated than in unweighted muscle. In vitro, lysosomotropic agents (eg, chloroquine, methylamine) did not lessen the increase in proteolysis caused by unweighting, but abolished the difference in proteolysis between denervated and unweighted muscle. Leucine methylester, an indicator of lysosome fragility, lowered latency more in denervated than in unweighted muscle. 3-Methyladenine, which inhibits phagosome formation, increased latency similarly in all muscles tested. Mersalyl, a thiol protease inhibitor, and 8-(diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8), which antagonizes sarcoplasmic reticulum release of Ca2+, reduced accelerated proteolysis caused by unweighting without diminishing the faster proteolysis due to denervation. Calcium ionophore (A23187) increased proteolysis more so in unweighted than control muscles whether or not Ca2+ was present. Different mechanisms of accelerated proteolysis were studied further by treating muscles in vivo for 24 hours with chloroquine or mersalyl. Chloroquine diminished atrophy of the denervated but not the unweighted muscle, whereas mersalyl prevented atrophy of the unweighted but not of the denervated muscle, both by inhibiting in vivo proteolysis. These results suggest that (1) atrophy of denervated, but not of unweighted, soleus muscle involves increased lysosomal proteolysis, possibly caused by greater permeability of the lysosome, and (2) cytosolic proteolysis is important in unweighting atrophy, involving some role of Ca2(+)-dependent proteolysis and/or thiol proteases.


Long-term outcome and factors influencing bridging plates for mandibular reconstruction.
Vascularized bone grafts have become the preferred method of mandibular reconstruction. However, the technique is considered to increase both the operating time and blood loss, which might be associated with an increased morbidity and mortality. We conducted a retrospective analysis of 100 consecutive patients who underwent immediate bridging plate reconstruction. The median follow-up duration was 70 months. The 5-year overall survival rate was 69.9%. Cox multivariate analysis revealed that red blood cell transfusion was an independent prognostic factor for the overall survival. The plate survival with no complications was 62.2% at 5 years. Anterolateral defects and preoperative radiotherapy emerged as an independent adverse factor for plate survival. The use of bridging plates is an option for lateral mandibular reconstruction with no preoperative irradiation to avoid the risk from blood transfusion.