Combined SEPT9 and BMP3 methylation in plasma for colorectal cancer early detection and screening in a Brazilian population.
Colorectal cancer (CRC) screening can help to reduce its incidence and mortality. Noninvasive strategies, such as plasma analysis of epigenetic alterations, can constitute important biomarkers of CRC detection. This study aimed to evaluate the plasma methylation status of SEPT9 and BMP3 promoters as biomarkers for detection of CRC and its precursor lesions in a Brazilian population. Plasma samples from 262 participants of the CRC screening program of Barretos Cancer Hospital who had a positive fecal occult blood test and underwent colonoscopy and cancer patients were analyzed. Participants were grouped according to the worst lesion detected in the colonoscopy. Cell-free circulating DNA (cfDNA) was bisulfite treated followed by the analysis of SEPT9 and BMP3 methylation status using a droplet digital PCR system (ddPCR). The best methylation cutoff value for group discrimination was calculated by receiver operating characteristic (ROC) curve analysis. Among the 262 participants, 38 were diagnosed with CRC, 46 with advanced adenomas 119 with nonadvanced adenomas, three with sessile serrated lesions, and 13 with hyperplastic polyps. In 43 participants, no lesion was detected in the colonoscopy and were used as controls. The CRC group showed the highest cfDNA concentration (10.4 ng/mL). For the SEPT9 gene, a cutoff of 2.5% (AUC = 0.681) that discriminates between CRC and the control group resulted in CRC sensitivity and specificity of 50% and 90%, respectively. Concerning the BMP3 gene, a cutoff of 2.3% (AUC = 0.576) showed 40% and 90% of sensitivity and specificity for CRC detection, respectively. Combining SEPT9, BMP3 status, and age over 60 years resulted in a better performance for detecting CRC (AUC = 0.845) than the individual gene models, yielding 80% and 81% of sensitivity and specificity, respectively. The present study suggests that a combination of SEPT9 and BMP3 plasma methylation, along with age over 60 years, showed the highest performance in detecting CRC in a Brazilian population. These noninvasive biomarkers can potentially serve as useful tools for CRC screening programs.


Dispersion of nanoparticles: from organic solvents to polymer solutions.
This work is devoted to a systematic study of nanoparticle dispersion by ultrasonication in different solutions: from organic solvents to polymer solutions. The cluster size of nanoparticles at different concentrations in both organic solvents and polymer solutions were directly characterized by Dynamic Light Scattering to study the effect of solid concentration, surfactant and polymer on the dispersion. It reveals that in stabilized suspensions, the smallest attainable size or aggregate size of nanoparticles is independent of solvent type and solid content over the tested range. Furthermore, nanoparticles in simple solvent and in polymer solutions had the similar evolution of cluster size and almost the same final size, which could be very helpful to optimize the dispersion of nanofillers in polymer solutions and nanocomposites. It is also shown that, with appropriate sonication amplitudes, the dispersion procedure developed for very dilute suspensions could be transferred to higher concentration suspensions or even to polymer suspensions.


Cloning and characterization of a mitochondrial glyoxalase II from Brassica juncea that is upregulated by NaCl, Zn, and ABA.
A cDNA (1061 bp) Bj glyII was cloned from a mannitol induced library of Brassica juncea. It encoded a protein of 335 amino acids with a molecular weight of 36.52 kDa. The deduced amino acid sequence of the clone showed 92% and 56% identity with Pennisetum and rice glyoxalase II, respectively, and 30% identity was observed with the human glyoxalase II. Search for the identical residues revealed the presence of highly conserved THHHXDH domain which is involved in zinc binding. p-NN and pSORT analysis of this sequence revealed a N-terminal mitochondrial target peptide. The cDNA was cloned in pMAL and a fusion protein with MBP (78 kDa) was expressed in Escherichia coli. The recombinant protein was purified approximately sixfold by affinity purification on amylose column and showed its pH optima at 7.0. The K(m) was determined to be 120 microM using S-d-lactoylglutathione as substrate. The expression of Bj glyII under various abiotic stress conditions showed that it is upregulated by salinity, heavy metal stress, and ABA.


Obesity and cancer.
Large-scale studies have demonstrated that obesity increases the risk of developing some forms of cancer. The association between obesity and cancer may result from factors such as fat distribution or sex hormone levels. Studies have also shown a relationship between a high-fat, low-fiber diet and cancer risk. High estrogen levels and low progesterone levels are associated with an increased risk of endometrial cancer. Obesity is known to raise estrogen levels and may lower progesterone levels. Obesity may increase the risk of breast cancer, but the evidence is less clear, since factors, such as age, country of origin, body-fat distribution, and family history, also play a major role in determining breast cancer risk. Sex hormones, insulin, and nutritional factors are also involved in the etiology of breast cancer. The incidence of lung cancer is inversely related to body weight.


Early warning of Ross River virus epidemics: combining surveillance data on climate and mosquitoes.
Ross River virus disease is spread by mosquitoes, and an average of 5000 people are infected each year in Australia. It is one of the few infectious diseases for which climate-based early warning systems could be developed. The aim of this study was to test whether supplementing routinely collected climate data with mosquito surveillance data could increase the accuracy of disease prediction models. We focused on a temperate region of Western Australia between July 1991 and June 1999. We developed "early" and "later" warning logistic regression models to test the sensitivity of data on climate (tide height, rainfall, sea surface temperature) and mosquito counts for predicting epidemics of disease. Climate data on their own were moderately sensitive (64%) for predicting epidemics during the early warning period. Addition of mosquito surveillance data increased the sensitivity of the early warning model to 90%. The later warning model had a sensitivity of 85%. We found that climate data are inexpensive and easy to collect and allow the prediction of Ross River virus disease epidemics within the time necessary to improve the effectiveness of public health responses. Mosquito surveillance data provide a more expensive early warning but add substantial predictive value.


Whole-Genome Sequencing and Annotation of Selected Lactobacillales Isolated from Commercial Cucumber Fermentation.
We report the whole-genome sequences and annotations of 42 Lactobacillales isolated from commercial cucumber fermentations performed in North Carolina (n = 34) and Minnesota (n = 9), USA. The isolates include representatives from 12 acid-producing species.


Photophobia in multiple sclerosis.
Photophobia has never been investigated in MS. In this pilot study we used photosensitivity questionnaire assessment (PAQ) to evaluate tolerability to light in 73 MS patients and 62 healthy controls. We identified a lower PAQ score and a higher number of photophobic subjects in MS than in controls. Moreover, clinical disability or previous optic neuritis did not predict the photosensitivity profile. Further studies to investigate the pathophysiological mechanisms underlying photophobia in MS are needed.


The Impact of an Inpatient Pancreatitis Service and Educational Intervention Program on the Outcome of Acute Pancreatitis.
We introduced an inpatient pancreatitis consultative service aimed to 1) provide guideline-based recommendations to acute pancreatitis inpatients and 2) educate inpatient teams on best practices for acute pancreatitis management. We assessed the impact of pancreatitis service on acute pancreatitis outcomes. Inpatients with acute pancreatitis (2008-2018) were included in this cohort study. Primary outcomes included length of stay and refeeding time. The educational intervention was a guideline-based decision support tool, reinforced at hospital-wide educational forums. In Part A (n = 965), we compared outcomes pre-service (2008-2010) to post-service (2012-2018), excluding 2011, when the pancreatitis service was introduced. In Part B (n = 720, 2012-2018), we divided patients into 2 groups based on if co-managed with the pancreatitis service, and compared outcomes, including subgroup analysis based on severity, focusing on mild acute pancreatitis. In Part A, for mild acute pancreatitis, length of stay (111 vs 88.4 h, P = .001), refeeding time (61.8 vs 47.4 h, P = .002), and infections (10.0% vs 1.87%, P < .001) were significantly improved after the pancreatitis service was introduced, with multivariable analysis showing reduced length of stay (odds ratio 0.83; 95% confidence interval, 0.82-0.84; P < .001) and refeeding time (odds ratio 0.75; 95% confidence interval, 0.74-0.77; P < .001). In Part B, for mild acute pancreatitis, refeeding time (44.2 vs 50.3 h, P = .123) and infections (5.58% vs 4.70%, P = .80) were similar in patients cared for without and with the service. Length of stay was higher in the pancreatitis service group (93.3 vs 81.2 h, P = .05), as they saw more gallstone acute pancreatitis patients who had greater length of stay and magnetic resonance cholangiopancreatography. In the post-service period, a majority of patients with moderate/severe acute pancreatitis and nearly all intensive care unit admits received care from the pancreatitis service. Implementation of an inpatient pancreatitis service was associated with improved outcomes in mild acute pancreatitis. Guideline-based educational interventions have a beneficial impact on management of mild acute pancreatitis by admitting teams even without pancreatitis consultation.


The neuro-ophthalmology trap: failure to diagnose.
A failure to diagnose was the basis for most of a series of 35 malpractice suits filed against ophthalmologists and other physicians. All of these cases presented problems in neuro-ophthalmologic diagnosis. Selected summaries illustrate typical diagnostic pitfalls. "Creative" consultation reports may be one effective prophylactic measure against such legal actions.


Primary cutaneous T-cell-rich B-cell lymphoma.
A 61-year-old man presented with a skin tumour in the right axilla of 2 months' duration. An excision biopsy revealed a malignant lymphoma, of diffuse mixed small and large cell type, morphologically suggestive of T-cell lymphoma, but shown to be a T-cell-rich B-cell lymphoma by subsequent immunohistochemical staining. A review of the literature revealed 47 cases of T-cell-rich B-cell lymphoma with descriptions of primary sites, 35 nodal and 12 extranodal, of which only one was a cutaneous primary.


In-vivo diffusion MRI protocol optimization for the chimpanzee brain and examination of aging effects on the primate optic nerve at 3T.
Diffusion MRI (dMRI) data acquisition protocols are well-established on modern high-field clinical scanners for human studies. However, these protocols are not suitable for the chimpanzee (or other large-brained mammals) because of its substantial difference in head geometry and brain volume compared with humans. Therefore, an optimal dMRI data acquisition protocol dedicated to chimpanzee neuroimaging is needed. A multi-shot (4 segments) double spin-echo echo-planar imaging (MS-EPI) sequence and a single-shot double spin-echo EPI (SS-EPI) sequence were optimized separately for in vivo dMRI data acquisition of chimpanzees using a clinical 3T scanner. Correction for severe susceptibility-induced image distortion and signal drop-off of the chimpanzee brain was performed and evaluated using FSL software. DTI indices in different brain regions and probabilistic tractography were compared. A separate DTI data set from n=34 chimpanzees (13 to 56 years old) was collected using the optimal protocol. Age-related changes in diffusivity indices of optic nerve fibers were evaluated. The SS-EPI sequence acquired dMRI data of the chimpanzee brain with approximately doubled the SNR as the MS-EPI sequence given the same scan time. The quality of white matter fiber tracking from the SS-EPI data was much higher than that from MS-EPI data. However, quantitative analysis of DTI indices showed no difference in most ROIs between the SS-EPI and MS-EPI sequences. The progressive evolution of diffusivity indices of optic nerves indicated mild changes in fiber bundles of chimpanzees aged 40 years and above. The single-shot EPI-based acquisition protocol provided better image quality of dMRI for chimpanzee brains and is recommended for in vivo dMRI study or clinical diagnosis of chimpanzees (or other large animals) using a clinical scanner. Also, the tendency of FA decrease or diffusivity increase in the optic nerve of aged chimpanzees was seen but did not show significant age-related changes, suggesting aging may have less impact on optic nerve fiber integrity of chimpanzees, in contrast to previous results for both macaque monkeys and humans.


Distribution of neuropeptides in the antennal lobes of male Spodoptera littoralis.
Olfaction is an important sensory modality that regulates a plethora of behavioural expressions in insects. Processing of olfactory information takes place in the primary olfactory centres of the brain, namely the antennal lobes (ALs). Neuropeptides have been shown to be present in the olfactory system of various insect species. In the present study, we analyse the distribution of tachykinin, FMRFamide-related peptides, allatotropin, allatostatin, myoinhibitory peptides and SIFamide in the AL of the male Egyptian cotton leafworm, Spodoptera littoralis. Immunocytochemical analyses revealed that most neuropeptides were expressed in different subpopulations of AL neurons. Their arborisation patterns within the AL suggest a significant role of neuropeptide signalling in the modulation of AL processing. In addition to local interneurons, our analysis also revealed a diversity of extrinsic peptidergic neurons that connected the antennal lobe with other brain centres. Their distributions suggest that extrinsic neurons perform various types of context-related modulation.


Activation of the cardiac endothelin system in left ventricular hypertrophy before onset of heart failure in TG(mREN2)27 rats.
To characterize the cardiac angiotensin and endothelin (ET) system in compensated left ventricular hypertrophy due to long standing arterial hypertension and to assess the role of angiotensin and ET converting enzymes in mediating the observed changes of angiotensin and ET levels, respectively. We studied the left ventricular renin-angiotensin system (RAS) and ET system in 20-week-old male transgenic hypertensive TG(mREN2)27 rats, a model of the monogenic renin-dependent form of severe hypertension. Age-matched Sprague-Dawley rats served as controls. TG(mREN2)27 rats exhibited left ventricular hypertrophy without signs of congestion. Transgene overexpression led to an activation of the tissue RAS with increased angiotensin II levels in spite of unchanged angiotensin converting enzyme (ACE) activity and ACE mRNA levels. ET-1 production was markedly increased in TG(mREN2)27 rats indicating that the ET-system was activated. Cardiac ET-1 in TG(mREN2)27 originated most likely from increased preproET-1 production because preproET-1 mRNA levels were increased but ET converting enzyme gene expression and activity were unchanged. Furthermore, ET-1 binding sites were significantly increased in TG(mREN2)27 rats without changes in K(D) values and ET(A)/ET(B) receptor ratios. ET(A) receptor gene expression was not altered whereas ET(B) receptor mRNA levels were up-regulated twofold in TG(mREN2)27 rats suggesting that ET(A) and ET(B) receptor expression may be regulated differentially. Cardiac ET and angiotensin systems are co-activated in compensated cardiac hypertrophy before onset of heart failure, and thus may be involved in the mechanism by which cardiac remodelling and progression of left ventricular dysfunction occur in TG(mREN2)27 rats.


DNA-binding property of recombinant capsid protein of Japanese encephalitis virus.
Japanese encephalitis virus (JEV) is a member of the Flaviviridae family, and it is capable of inducing febrile syndrome, encephalitis and death. In this study, the cDNA of JEV-YL capsid (core) protein were cloned and expressed in E. coli. Three expressed recombinant clones (pET32/CORE, pET32/CD and pET32/C2D) including different parts of capsid protein, were constructed from JEV cDNA clone, pJE-S. These recombinant proteins (34, 31, and 26 kDa, respectively) containing an amino terminal tag of six histidines were isolated by the nickel chelate affinity chromatography and the purified products were identified by Western blotting with anti-serum of JEV-infected swine. To examine DNA binding property of the capsid protein, the purified recombinant proteins were assayed by electrophoretic mobility shift assay. The results showed the capsid proteins had the abilities to bind DNA, except the prominent product of pET32/C2D, which had deletion in the middle hydrophobic region of capsid protein and revealed the coding region of the amino acid, F46 to P61, is mediating the DNA binding ability. This study suggests a possible regulatory role for capsid protein in the pathway of JEV infection.


Pre-operative nutrition assessments do not improve outcomes in cerebral palsy patients undergoing varus derotational osteotomy.
Pre-operative nutritional assessments have been used as a "cornerstone" to help optimize nutritional status and weight in children with cerebral palsy (CP) to lower the risk of postoperative complications. However, the potential value of nutritional assessments on surgical outcomes in patients with CP undergoing major orthopedic surgery remains unproven.Do pre-operative nutritional assessments reduce complication rates of varus derotational osteotomy surgery in children with CP? Are complication rates higher in patients with a gastrostomy tube (G-tube) and can they be decreased by pre-operative nutritional assessment?One-hundred fifty-five patients with CP who underwent varus derotational osteotomy from January 1, 2012 through December 31, 2017 at a tertiary pediatric hospital with minimum 6 months follow-up were retrospectively identified. One-hundred-ten (71%) were categorized as "non-ambulatory" (Gross Motor Function Classification System [GMFCS] IV-V), and 45 (29%) as "ambulatory" (GMFCS I-III). Variables assessed included age, GMFCS level, G-tube, body mass index (BMI) percentile, complications, and if patients underwent pre-operative nutritional assessment.One-hundred-eleven patients (71.6%) underwent pre-operative nutritional assessment. Sixty-two of 155 patients (40.0%) had G-tubes. In non-ambulatory patients with G-tubes, BMI percentile changes were not significantly different between patients with a pre-operative nutritional assessment compared to those without at 1 (P = .58), 3 (P = .61), 6 (P = .28), and 12 months (P = .21) postoperatively. In non-ambulatory patients who underwent pre-operative nutritional assessment, BMI percentile changes were not significantly different between those with and without G-tubes at 1 (P = .61), 3 (P = .71), 6 (P = .19), and 12 months (P = .10). Pulmonary complication rates were significantly higher in non-ambulatory patients with G-tubes than in non-ambulatory patients without G-tubes (20% vs 4%, P = .03). Pre-operative nutritional assessments did not influence postoperative complication rates for non-ambulatory patients with or without a G-tube (P = .12 and P = .16, respectively). No differences were found in postoperative complications between ambulatory patients with and without G-tubes (P = .45) or between ambulatory patients with or without nutritional assessments (P = .99).Nutritional assessments, which may improve long term patient nutrition, should not delay hip surgery in patients with CP and progressive lower extremity deformity. Patients and their families are unlikely to derive any short-term nutritional improvement using routine pre-operative evaluation and surgical outcomes are unlikely to be improved.Level of Evidence: III, retrospective comparative.


In vitro impact of bisphenols BPA, BPF, BPAF and 17β-estradiol (E2) on human monocyte-derived dendritic cell generation, maturation and function.
Bisphenols (BPs) are widely spread pollutants that act as estrogen-like endocrine disruptors and are potentially affecting human health on a long run. We explored the effects of BPA, BPF and BPAF, on in vitro differentiation and maturation of MDDCs. Monocytes were treated with 17β-estradiol (E2) and each BP at the beginning of their differentiation into iMDDCs. We found that 10 and 50 μM of BPA and BPF, 10 and 30μM of BPAF and 10 and 50 nM of E2 did not affect cell viability. However, 50 μM of BPA and BPF, as well as 10 and 30 μM of BPAF, significantly decreased the endocytotic capacity of iMDDCs. Both, BPA (50 μM) and BPAF (30 μM) decreased the expression of CD1a and increased the amount of DC-SIGN molecules on iMDDCs. The E2 pre-treatment moderately decreased expression of CD80, CD86 and CD83 co-stimulatory molecules while increasing the numbers of HLA-DR on mMDDCs. Only BPAF significantly influenced the expression of CD80 and CD86 (both decreased), as well as CD83 and HLA-DR molecules (both increased) on mMDDCs. In addition, BPAF modulated DC maturation signaling pathways by lowering the phosphorylation of p65 NF-κB (nuclear factor-kappaB) and ERK (extracellular signal regulated kinase) 1/2 proteins. Consequently, the in vitro proliferation of allogeneic T cells, stimulated with differently pre-treated iMDDCs and mMDDCs, was significantly reduced only in case of BPAF.


Treatment of idiopathic thrombocytic purpura in pregnancy by high-dose intravenous immunoglobulin.
ITP in pregnancy may lead to fetal thrombocytopenia caused by the transplacental passage of maternal antiplatelet antibody. The most hazardous complication in the infant is intracranial hemorrhage. In addition ITP in pregnancy is reported to be associated with an increased abortion rate and an elevated fetal morbidity and mortality. Therefore obstetric management must aim at increasing maternal and fetal platelets. Several therapeutic approaches to the treatment of ITP in pregnancy are evaluated. Two cases of ITP in pregnancy are reported. Administration of high-dose intravenous immunoglobulin is introduced as a new therapy for ITP in pregnancy. The rapid reversal of thrombocytopenia following immunoglobulin G administration suggests that it is useful especially as emergency treatment for ITP in pregnancy.


Evaluation of time, attendance of medical staff, and resources during radiotherapy for breast cancer patients. The DEGRO-QUIRO trial.
To conform to recommendations regarding the treatment of breast cancer, an estimation of costs and personnel to assure treatment is required. To date no recommendations based on real time measurements are available. The DEGRO (German Society of Radiation Oncology), therefore, initiated a prospective multicenter evaluation of core procedures of radiotherapy. In this analysis, the results regarding human resources and room occupation during the treatment of breast cancer are presented. Three academic radiation oncology centers (Erlangen, Münster, Mannheim) prospectively documented their workflow and working time for all breast cancer patients from July-October 2008. Subsequently, a statistical analysis was performed. The longest working time of physicians was the definition of the target volume and organs at risk (mean 33 min). Furthermore, physicians needed much time for general tasks, which included conversations. Physicists needed the most time for treatment planning and authorization (64 min), whereas technicians were mostly needed in day-to-day radiotherapy treatment (15 min, 31 min including verification). Despite significant differences in specific steps between centers, overall working times and room occupation were comparable and representative. Special procedures (intraoperative radiotherapy/multicatheter brachytherapy) required considerable amounts of additional working time of physicians and physicists. In this prospective analysis, data of human resources and room occupation during treatment of breast cancer are presented for the first time. Each patient consumes about 12 h of human resources for treatment and 3.75 h for general tasks (physicians 4.7 h, physicists 1.8 h, and technicians 9.2 h).


New species and records of Pseudolanurgus (Coleoptera: Curculionidae, Scolytinae) from Tanzania and Madagascar.
The recently established genus Pseudolanurgus Jordal, 2021 included one species from Democratic Republic of the Congo and two from Madagascar. Two more species are here described as new to science: Pseudolanurgus mystax sp. nov. from the United Republic of Tanzania and Pseudolanurgus asperatus sp. nov. from Madagascar. A key to all five species is provided along with photos of all species.


Oxidative stress and antioxidant enzymes activities in the African catfish, Clarias gariepinus, experimentally challenged with Escherichia coli and Vibrio fischeri.
The impacts of bacterial infection on cultivated fish species, African catfish, were investigated using oxidative stress biomarkers [lipid peroxidation (LPO) and protein carbonylation] and the activities of important antioxidant/detoxifying enzymes [catalase and glutathione S-transferase (GST)]. Fish were inoculated via oral gavage with one of the following treatments: 1 × 10(5) CFU/ml of Escherichia coli (EC1), 2 × 10(5) CFU/ml of E. coli (EC2), 1 × 10(5) CFU/ml of Vibrio fischeri (V1), 2 × 10(5) CFU/ml of V. fischeri (V2), gavaged with distilled water and not gavaged. Fish were maintained in the laboratory for 7 days after the bacterial inoculation, and the levels of LPO, protein carbonylation, GST, and catalase activities were determined in the muscle, gills, and liver of fish. Fish inoculated with bacteria (either E. coli or V. fischeri) had a significant higher levels of tissue LPO, protein carbonylation, and GST activities in a tissue-specific pattern (liver > muscle > gills). This appears to be related with the levels of bacterial inoculation, with effects more pronounced in fish inoculated with either EC2 or V2. The catalase activity did not differ significantly between the inoculated and fish that were not inoculated. The results of this study indicate that bacterial inoculation could result in oxidative stress in fish, and liver has a higher rate of oxidative stress per mg tissue compared to the gills and the muscle.


Mental health and governmental response policy evaluation on COVID-19 based on vaccination status in Republic of Korea.
The coronavirus disease (COVID-19) pandemic has continued since the outbreak in December 2019. People experience depression and anxiety due to government policies and restrictions on physical activity due to the COVID-19 pandemic. This study aimed to compare and analyze people's experiences of COVID-19 blues, sports policy awareness, and participation intention according to their vaccination status. This quantitative study used an online survey to collect demographic information, vaccination status, and variables. Data validity and reliability were verified through confirmatory factor analysis, and Cronbach's alpha coefficients were calculated using SPSS/AMOS 23.0. Finally, this comparative study was conducted using multivariate analysis of variance to investigate the differences in the dependent variables between the groups. The vaccinated group had higher scores for all factors related to COVID-19 blues (F = 19.147; p < .05; partial η2 = .046) and government policy (market responsiveness: F = 5.669, p < .05, partial η2 = .014; policy performance: F = 6.997, p < .05, partial η2 = .017; policy satisfaction: F = 7.647, p < .05, partial η2 = .019), apart from the intention to participate in sports (F = .014, p > .05, partial η2 = .000); these results demonstrate that people with COVID-19 blues and relatively high confidence in government quarantine policies were more likely to be vaccinated. In addition, all participants gave sports-participation intention the highest rating, regardless of their vaccination status; this reflects the current situation, in which individual activities are limited. This study analyzed the mental health of vaccinated and unvaccinated groups in Korean adult men, their perceptions of government policies, and their willingness to engage in physical activity. The findings are meaningful and highlight useful directions for future research. This study provides evidence which can help alleviate the mental damage caused by government quarantine policies and enable a better understanding of the COVID-19 pandemic. The results of this study provide important data for understanding the COVID-19 pandemic.


Potential role of growth factors in the management of spinal cord injury.
To review central nervous system growth factors and their therapeutic potential and clinical translation into spinal cord injury (SCI), as well as the challenges that have been encountered during clinical development. A systemic review of the available current and historical literature regarding central nervous system growth factors and clinical trials regarding their use in spinal cord injury was conducted. The effectiveness of administering growth factors as a potential therapeutic strategy for SCI has been tested with the use of brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, neurotrophin 3, and neurotrophin-4/5. Delivery of growth factors to injured SC has been tested by numerous methods. Unfortunately, most of clinical trials at this time are uncontrolled and have questionable results because of lack of efficacy and/or unacceptable side effects. There is promise in the use of specific growth factors therapeutically for SCI. However, more studies involving neuronal regeneration and functional recovery are needed, as well the development of delivery methods that allow sufficient quantity of growth factors while restricting their distribution to target sites.


Ability of fat and fat-free mass percentages to predict functional disability in older men and women.
Previous studies suggest an association between body composition and declining functional ability in older people. This study examined the relation between functional disability and percentage of fat mass (FM) and percentage of fat-free mass (FFM) in older men and women. Cross-sectional and prospective. Rancho Bernardo, California. Subjects consisted of 1,051 ambulatory, community-dwelling Caucasian men and women, age 55 to 92, who attended a clinic visit between 1988 and 1992 and a subsequent clinic visit between 1992 and 1996. Measured at both visits, percentage of fat mass and percentage of lean body mass were estimated by bioelectric impedance analysis and functional disability was ascertained by self-administered questionnaire. Functional disability was dichotomized into those having any difficulty with a set of tasks versus those having no difficulty with the tasks. Two measures of functional disability were used: "lower body" disability, consisting of two lower motor tasks (walking 2-3 blocks and climbing up 10 stairs) and "overall" disability, consisting of nine tasks representing upper and lower body function and mobility. Compared with men, women were more likely to report both lower body and overall functional disability (P=.001). Cross-sectionally, a significant positive association was shown between fat mass and overall functional disability and a significant negative association was shown between FFM and overall functional disability in both men and women. Prospectively, increased percentage of body fat and decreased percentage of FFM were significantly associated with decreased functional ability in both women and men. All results were adjusted for age, smoking, alcohol use, physical activity, current estrogen use, depression, chronic disease, and education. Increased percentage of fat mass and decreased percentage of FFM are associated with greater functional disability in older men and women. Further research is needed to assess the relative importance of decreasing fat percentage or increasing fat-free percentage to preserve or improve functional ability in older people.


Preparation of nano sustained-release fertilizer using natural degradable polymer polylactic acid by coaxial electrospinning.
Polylactic acid (PLA) is a novel biodegradable material that is widely used in fields like medicine, petrochemicals, disposable products, and has played significant role in the fast-growing agriculture sector in recent years. In this study, nanoscale sustained-release urea fiber materials were successfully fabricated by coaxial electrospinning by encapsulating urea inside polylactic acid fibers. The effects of different concentrations of PLA and urea on the preparation of fibrous membranes as well as the effects of different concentrations of PH and variations in temperature on the sustained release were investigated. The experimental results showed that the proposed method was feasible and the urea fiber membranes acidic and basic conditions as well as elevated temperatures. The sustained release time for the urea was as long as 84 d. Scanning electron microscopy and Fourier transform infrared spectrophotometry were employed to characterize the morphology of the electrospun nanofibers. Thermogravimetric analysis and differential scanning calorimetry showed that the release system was thermally stable up to a temperature of 126 °C, and urea concentration was determined by UV-Vis spectrophotometry. This method has broad application prospects in agricultural production and provides a more rational fertilizer choice for soil-free cultivation.


Pre-ictal bispectral index has a positive correlation with seizure duration during electroconvulsive therapy.
Propofol anesthesia increases the seizure threshold of patients receiving electroconvulsive therapy. Excessive neuronal suppression could result in an unacceptably short seizure. We sought to identify the correlation between the pre-ictal bispectral index (BIS) score and seizure duration in patients receiving electroconvulsive therapy under propofol anesthesia. BIS was monitored in 38 psychotically depressed patients. Anesthesia was induced by a bolus injection of 1 mg/kg of propofol. The duration of muscular and electroencephalographic seizure was measured during the therapy. The BIS immediately before the electrical shock was 54 +/- 13. Both muscular and electroencephalographic seizure durations had a positive correlation with pre-ictal BIS (r = 0.68 and 0.73, respectively; P < 0.01). After the electrically induced seizure, BIS decreased to 30 +/- 8, reflecting post-ictal suppression. BIS scores when the patients had awakened after the seizure had a wide variation (range, 29-81; mean, 45; SD, 13). In conclusion, seizure duration has a positive correlation with BIS immediately before electrical shock; however, BIS may not be an accurate predictor of awakening after electrical shock. Pre-ictal bispectral index had a positive correlation with seizure duration and could be useful to prevent an unacceptably short seizure in electroconvulsive therapy under propofol anesthesia.


Is kinesiophobia related to fear of falling, dizziness disability, and migraine disability in patients with migraine?
Kinesiophobia is a common symptom associated with high disability, and has been observed in patients with migraine. However, the association between kinesiophobia and clinical factors in this population is unknown. To assess the fear of falling, dizziness disability, and migraine disability in patients with migraine, considering the presence of kinesiophobia. Eighty patients with migraine completed the Tampa Scale for Kinesiophobia and were divided into two groups according to the questionnaire cutoff point: migraine without kinesiophobia (MoK, n = 39) and migraine with kinesiophobia (MK, n = 41). Fear of falling, dizziness disability, and migraine disability were assessed in both groups using validated questionnaires. The MK group presented higher scores on dizziness disability, fear of falling, and migraine disability compared to the MoK (p < .05). Kinesiophobia can explain 29% of the variance in dizziness disability and 18% of migraine disability. Both kinesiophobia and the presence of dizziness can explain 14% of fear of falling variability. Also, kinesiophobia is associated with the risk of presenting fear of falling (Prevalence Ratio = 2.4, p = .012), and migraine disability (Prevalence Ratio = 2.6, p = .01). The presence of kinesiophobia should be considered in clinical practice when evaluating migraine, as it is associated with increased levels of fear of falling, dizziness disability, and migraine disability.


[A case of adenocarcinoma of the thymus].
We report an adenocarcinoma of the thymus in a 39-year-old male. The patient presented with chest pain, and the chest X-ray film and chest CT showed an abnormal mass in the mediastinum. A preoperative clinical diagnosis of invasive thymoma was suspected. The tumor was resected along with the pleura and pericardium. The pathological findings were compatible with those of adenocarcinoma of the thymus. Despite a thorough examination, no primary tumor could be found. An adenocarcinoma of the thymus is rare and to the authors knowledge there are few previous reports in the literature.


Immunohistochemical expression of activated caspase-3 in human myocardial infarction.
There is mounting evidence that apoptosis is important in the pathogenesis of myocardial infarction (MI). One of the key events in the process of apoptosis is activation of caspase-3. Much attention has been recently paid to caspase inhibition as a potential treatment for ischemic cardiac disease. To predict the long-term effect of such treatment, it is essential to understand the significance of caspase-3 in the evolution of MI. Our aim was therefore to analyze immunohistochemical expression of activated caspase-3 in MI. Our study included autopsy samples of infarcted heart tissue from 50 patients with MI. Immunohistochemistry was performed by a sensitive peroxidase-streptavidin method on formalin-fixed, paraffin-embedded tissue, using monoclonal antibodies against activated (cleaved) caspase-3. We found caspase-3-positive myocytes in 18 MI less than 24 h old and in 3 MI that were presumably 48 h old. Their density (number of labeled myocytes/mm(2)) was greater in patients who received reperfusion treatment (mean 0.160+/-0.373 vs 0.025+/-0.037, p=0.06). In MI older than 48 h, positive reaction was observed in neutrophil granulocytes in the interstitium and, in subacute MI, it was observed in mononuclear inflammatory cells, myofibroblasts, and vascular endothelial cells. Our results suggest that apoptosis of myocytes is an important mode of cell death in the early MI, being enhanced in patients who received reperfusion treatment. After 48 h, apoptosis is an important mechanism of the clearance of neutrophil granulocytes and other inflammatory cells and of scar formation. Treatment with caspase inhibitors therefore will not only affect myocyte loss but will also interfere with the clearance of neutrophils and with the transformation of granulation tissue into a scar.


Impact of lockdown for SARS-CoV-2 (COVID-19) on surgical site infection rates: a monocentric observational cohort study.
Surgical site infections are the most common in-hospital acquired infections. The aim of this study and the primary endpoint is to evaluate how the measures to reduce the SARS-CoV-2 spreading affected the superficial and deep SSI rate. A total of 541 patients were included. Of those, 198 from March to April 2018, 220 from March till April 2019 and 123 in the COVID-19 era from March to April 2020. The primary endpoint occurred in 39 over 541 patients. In COVID-19 era, we reported a lower rate of global SSIs (3.3% vs. 8.4%; p 0.035), few patients developed a superficial SSIs (0.8% vs. 3.4%; p 0.018) and none experienced deep SSIs (0% vs. 3.4%; p 0.025). Comparing the previous two "COVID-19-free" years, no significative differences were reported. At multivariate analysis, the measures to reduce the SARS-CoV-2 spread (OR 0.368; p 0.05) were independently associated with the reduction for total, superficial and deep SSIs. Moreover, the presence of drains (OR 4.99; p 0.009) and a Type III-IV of SWC (OR 1.8; p 0.001) demonstrated a worse effect regarding the primary endpoint. Furthermore, the presence of the drain was not associated with an increased risk of superficial and deep SSIs. In this study, we provided important insights into the superficial and deep SSIs risk assessment for patients who underwent surgery. Simple and easily viable precautions such as wearing surgical masks and the restriction of visitors emerged as promising tools for the reduction of SSIs risk.


In vivo pharmacokinetics and in vitro pharmacodynamics of nepafenac, amfenac, ketorolac, and bromfenac.
To evaluate the aqueous humor concentrations and cyclooxygenase (COX) inhibitory activities of nepafenac, amfenac, ketorolac, and bromfenac after topical ocular administration of Nevanac (nepafenac 0.1%), Acular LS (ketorolac 0.4%), or Xibrom (bromfenac 0.09%). Five private ophthalmology practices throughout the United States. Patients requiring cataract extraction were randomized to 1 of 3 treatment groups: Nevanac, Acular LS, or Xibrom. Patients were administered 1 drop of the test drug 30, 60, 120, 180, or 240 minutes before cataract surgery. At the time of paracentesis, an aqueous humor sample was collected and later analyzed for drug concentration. In addition, COX-1 (homeostatic) and COX-2 (inducible) inhibitory activities of nepafenac, amfenac, ketorolac, and bromfenac were determined via the in vitro measurement of prostaglandin E(2) (PGE(2)) inhibition. Seventy-five patients participated in the study. The prodrug nepafenac had the shortest time to peak concentration and the greatest peak aqueous humor concentration (C(max)). The C(max) of nepafenac was significantly higher than that of the other drugs (P<.05), including the higher-concentration ketorolac (0.4%). The area under the curve (AUC) of nepafenac was significantly higher (P<.05) than the AUCs of amfenac, ketorolac, and bromfenac. The combined AUCs of nepafenac and amfenac were the highest of all drugs tested (P<.05). Ketorolac showed the most potent COX-1 inhibition, whereas amfenac was the most potent COX-2 inhibitor. The PGE(2) aqueous humor levels of each study medication were highly variable; as a result, meaningful interpretation of the data was not possible. Nepafenac showed significantly greater ocular bioavailability and amfenac demonstrated greater potency at COX-2 inhibition than ketorolac or bromfenac.


Genome Sequence of Highly Pathogenic Avian Influenza Virus A/Chicken/North Kazakhstan/184/2020 (H5N8).
The influenza virus strain A/chicken/North Kazakhstan/184/2020 (H5N8) was isolated in North Kazakhstan during a highly pathogenic avian influenza outbreak in 2020. This study aimed to obtain the complete genome sequence of the isolate.


SARS-CoV-2 Antibody Avidity Responses in COVID-19 Patients and Convalescent Plasma Donors.
Convalescent plasma therapy is a leading treatment for conferring temporary immunity to COVID-19-susceptible individuals or for use as post-exposure prophylaxis. However, not all recovered patients develop adequate antibody titers for donation and the relationship between avidity and neutralizing titers is currently not well understood. SARS-CoV-2 anti-spike and anti-nucleocapsid IgG titers and avidity were measured in a longitudinal cohort of COVID-19 hospitalized patients (n = 16 individuals) and a cross-sectional sample of convalescent plasma donors (n = 130). Epidemiologic correlates of avidity were examined in donors by linear regression. The association of avidity and a high neutralizing titer (NT) were also assessed in donors using modified Poisson regression. Antibody avidity increased over duration of infection and remained elevated. In convalescent plasma donors, higher levels of anti-spike avidity were associated with older age, male sex, and hospitalization. Higher NTs had a stronger positive correlation with anti-spike IgG avidity (Spearman ρ = 0.386; P < .001) than with anti-nucleocapsid IgG avidity (Spearman ρ = 0.211; P = .026). Increasing levels of anti-spike IgG avidity were associated with high NT (≥160) (adjusted prevalence ratio = 1.58 [95% confidence interval = 1.19-2.12]), independent of age, sex, and hospitalization. SARS-CoV-2 antibody avidity correlated with duration of infection and higher neutralizing titers, suggesting a potential alternative screening parameter for identifying optimal convalescent plasma donors.


Activation of bleomycin A2 to a DNA-damaging intermediate by phorbol ester-stimulated human polymorphonuclear leukocytes.
Metabolically stimulated polymorphonuclear leukocytes (PMNs) generate reactive oxygen metabolites that are capable not only of damaging biomolecules but also of possibly activating exogenous chemicals to reactive intermediates which interact with target molecules. This study examined this later concept and the results demonstrated that the interaction of bleomycin A2 with phorbol ester-stimulated human PMNs resulted in DNA deoxyribose cleavage, a process mediated by an activated bleomycin intermediate. Superoxide dismutase (SOD) significantly inhibited bleomycin-mediated DNA deoxyribose cleavage, indicating the involvement of reactive oxygen. Based on these observations it is plausible that other chemicals, including carcinogens, may be activated by metabolically stimulated PMNs to intermediates which react with biomolecules.


The radiological interpretation of possible microbleeds after moderate or severe traumatic brain injury: a longitudinal study.
In order to augment the certainty of the radiological interpretation of "possible microbleeds" after traumatic brain injury (TBI), we assessed their longitudinal evolution on 3-T SWI in patients with moderate/severe TBI. Standardized 3-T SWI and T1-weighted imaging were obtained 3 and 26 weeks after TBI in 31 patients. Their microbleeds were computer-aided detected and classified by a neuroradiologist as no, possible, or definite at baseline and follow-up, separately (single-scan evaluation). Thereafter, the classifications were re-evaluated after comparison between the time-points (post-comparison evaluation). We selected the possible microbleeds at baseline at single-scan evaluation and recorded their post-comparison classification at follow-up. Of the 1038 microbleeds at baseline, 173 were possible microbleeds. Of these, 53.8% corresponded to no microbleed at follow-up. At follow-up, 30.6% were possible and 15.6% were definite. Of the 120 differences between baseline and follow-up, 10% showed evidence of a pathophysiological change over time. Proximity to extra-axial injury and proximity to definite microbleeds were independently predictive of becoming a definite microbleed at follow-up. The reclassification level differed between anatomical locations. Our findings support disregarding possible microbleeds in the absence of clinical consequences. In selected cases, however, a follow-up SWI-scan could be considered to exclude evolution into a definite microbleed.


How mutualisms arise in phytoplankton communities: building eco-evolutionary principles for aquatic microbes.
Extensive sampling and metagenomics analyses of plankton communities across all aquatic environments are beginning to provide insights into the ecology of microbial communities. In particular, the importance of metabolic exchanges that provide a foundation for ecological interactions between microorganisms has emerged as a key factor in forging such communities. Here we show how both studies of environmental samples and physiological experimentation in the laboratory with defined microbial co-cultures are being used to decipher the metabolic and molecular underpinnings of such exchanges. In addition, we explain how metabolic modelling may be used to conduct investigations in reverse, deducing novel molecular exchanges from analysis of large-scale data sets, which can identify persistently co-occurring species. Finally, we consider how knowledge of microbial community ecology can be built into evolutionary theories tailored to these species' unique lifestyles. We propose a novel model for the evolution of metabolic auxotrophy in microorganisms that arises as a result of symbiosis, termed the Foraging-to-Farming hypothesis. The model has testable predictions, fits several known examples of mutualism in the aquatic world, and sheds light on how interactions, which cement dependencies within communities of microorganisms, might be initiated.


Novel lipase-catalysed highly selective acetylation studies on D-arabino- and D-threo-polyhydroxyalkyltriazoles.
Capabilities of lipases from Candida antarctica, Candida rugosa and porcine pancreas have been evaluated for regioselective acetylation of 2-phenyl-4-(D-arabino-tetrahydroxybutyl)-2H-1,2,3-triazole, 2-phenyl-4-(D-arabino-O-1',2'-isopropylidene-3',4'-dihydroxybutyl)-2H-1,2,3-triazole and 2-phenyl-4-(D-threo-trihydroxypropyl)-2H-1,2,3-triazole, precursors for the synthesis of triazolylacyclonucleosides. C. antarctica lipase and porcine pancreatic lipase exhibited exclusive selectivity for the acetylation of primary hydroxyl group over secondary hydroxyl group(s) in all the three cases.


Epistatic effect of IL1A and IL4RA genes on the risk of atopy.
Several studies have demonstrated a linkage or association of the atopic phenotype with T-cell cytokine genes involved in the regulation of the TH1/TH2 balance (eg, IL4, IL13, and their common receptor, IL4RA). We have recently shown that polymorphism of the pro-inflammatory cytokine IL1A gene is strongly associated with atopy. We now examined whether the polymorphisms of IL1A (G/T at +4845) and IL4RA (T/C at +22446) would show an epistatic effect on the risk of atopy. Skin prick tests and gene polymorphism analyses were performed in a population-based sample of asthmatic and nonasthmatic subjects. Our results showed that in the nonasthmatic group the previously described elevated risk of atopy in noncarriers of allele T of IL1A (ie, having the genotype GG) was restricted to individuals who were also noncarriers of allele C of IL4RA (genotype TT). This finding applies to the general population of Finland, where 3.3% of adults are asthmatic. These data suggest that the IL1A and IL4RA genes show an epistatic effect on the risk of atopy.


Inhibition of Helicobacter pylori infection in humans by Lactobacillus reuteri ATCC 55730 and effect on eradication therapy: a pilot study.
Several studies report an inhibitory effect of probiotics on Helicobacter pylori. To test whether Lactobacillus reuteri ATCC 55730 reduces H. pylori intragastric load in vivo, decreases dyspeptic symptoms, and affects eradication rates after conventional treatment. In a double-blind placebo-controlled study, 40 H. pylori-positive subjects were given L. reuteri once a day for 4 weeks or placebo. All underwent upper endoscopy, (13)C-urea breath test, and H. pylori stool antigen determination at entry and (13)C-urea breath test and H. pylori stool antigen (used as both qualitative and semiquantitative markers) after 4 weeks of treatment. Sequential treatment was administered subsequently to all. In vivo, L. reuteri reduces H. pylori load as semiquantitatively assessed by both (13)C-urea breath test delta-value and H. pylori stool antigen quantification after 4 weeks of treatment (p < .05). No change was shown in patients receiving placebo. L. reuteri administration was followed by a significant decrease in the Gastrointestinal Symptom Rating Scale as compared to pretreatment value (p < .05) that was not present in those receiving placebo (p = not significant). No difference in eradication rates was observed. L. reuteri effectively suppresses H. pylori infection in humans and decreases the occurrence of dyspeptic symptoms. Nevertheless, it does not seem to affect antibiotic therapy outcome.


Mitochondrial genes in Podospora anserina: recombination and linkage.
A fifth cytoplasmic mutation (capr 1) obtained in Podospora anserina is described. In addition to chloramphenicol resistance it confers a strong deficiency in cytochrome aa3 and impairs the germination of ascospores. Genetic analysis shows: 1) strict maternal inheritance of (capr 1) allele; 2) selection against the (capr 1) allele as well in sexual crosses as during vegetative growth; 3) complete reversion of this selection by even low concentration of CAP. On the basis of their cytoplasmic inheritance and altered cytochrome spectra the five cytoplasmic mutations are assumed to be mitochondrial. Analysis of crosses between them allows to class them in 3 loci, 2 of which being closely linked.


Normal human immune peritoneal cells: phenotypic characteristics.
Normal human peritoneal cells (PC) collected from patients with calculous cholecystitis without clinically detectable inflammatory changes were characterized morphologically, histochemically and phenotypically by means of monoclonal antibodies. The PC consisted of 45% of monocytes/macrophages (M718 + cells). Thirty-five per cent of PC were esterase-positive and 23% acid phosphatase positive. Forty-five per cent of PC adhered to glass surface. In the lymphocyte population, 2% of CD22 B lymphocytes (M738 +) and 42% CD2 T lymphocytes (M720+) were found. CD4/CD8 ratio was 0.4. There were 8% of Leu7 + cells. The PC did not reveal interleukin 2 (OKT26a +) and transferrin receptors (OKT9 +) on their surface. No blast cells were detected in the PC suspension. Approximately 49% of the PC expressed Ia antigens (OKIa1 +). Two per cent of S100 positive dendritic cells (Z311 +) were found. Peritoneal fluid contained 9% of granulocytes, mostly neutrophils. Two per cent of PC were free mesothelial cells (M717 +). We conclude that human peritoneal cavity contains a cell population significantly differing from that which is present in peripheral blood, which strongly suggests a non-random cell accumulation in the peritoneum. Lack of any activated cells indicates that under normal conditions the peritoneum lavage fluid contains a steady-state population. We conclude that the normal peritoneal fluid cells represent a heterogeneous population capable of reacting to various antigens entering the cavity from the gut.


Life-history evolution in Anodonta piscinalis (Mollusca, Pelecypoda) : Correlation of parameters.
The correlations between certain life-history parameters (reproductive effort, reproductive life-span, age of first reproduction, general growth index, variation in juvenile survival, availability of resources) were studied in 13 populations of the mussel Anodonta piscinalis in south-western Finland in 1975 and 1976Reproductive life-span correlated positively (r s=0,823, P<0.001) with variation in juvenile survival. The average availability of resources correlated negatively both with the reproductive life-span (r s=-0.841, P<0.001 after the variation by juvenile survival had been deleted) and variation in juvenile survival (r s=-0.676, P<0.05).The reproductive effort for female mussels at each site was computed by comparing body weight of reproductive females with body weights of non-reproductive individuals. Availability of resources was much higher in 1976 than in 1975. Consequently, the reproductive effort, an index of the strain of reproduction, was higher in 1975 than in 1976. In 1975 there was a significant correlation between reproductive effort and the length of the reproductive life-span (-0.727, -0.806) and also with the reproductive effort and the variation in juvenile survival (-0.718, -0.758) in females of the length of 60 mm and 70 mm respectively. In 1976, when availability of resources was better, such correlations were not found.Spatial and temporal change in the intake of resources complicates applicability of the principle of resource allocation in the theory of life-history evolution. Studying the mere allocation is not enough if the intake of resources varies in the groups studied. The ratio ovary weight/body weight is a dubious measure of reproductive effort in comparative studies when the input of resources can vary, and this possibility can be ruled out only exceptionally.Correlation between growth and reproductive effort was positive, obviously because both are important components in creating high reproductive capacity. In 1975 reproductive effort increased with size (age). Change in reproductive effort correlated with reproductive life-span (r s=-0.633, P<0.05).The following parameters occurred together: short reproductive life-span, low age of first reproduction, high reproductive effort, rapid growth and high clutch size. They were realized at sites where the availability of resources was good and variation in juvenile survival was low-i.e. the environment was stable. The results conflict with the prediction of the theory of r and K-selection.


Family environment, not heredity, accounts for family resemblances in food preferences and attitudes: a twin study.
Monozygotic and same-sex dizygotic twin pairs reported on their food preferences, the variety of foods of the same general category (e.g. types of soup) in their diet, and their concern about contact of their food with disgusting or other unacceptable substances (contamination sensitivity). Although there was substantial resemblance between siblings for many of these items, there was no clear evidence for a heritable component on any item. The only case for which there was an interpretable and significantly greater resemblance among monozygotic than among dizygotic twins (out of 23 questions) was preferred degree of hotness resulting from chili pepper in foods. These results confirm the prediction that in omnivorous animals, such as humans, genetic predispositions will be minimal with respect to food. The modest sibling resemblances on a number of measures are primarily attributable to a shared environment.


Two new RHD alleles with deletions spanning multiple exons.
The most common large-deletion RHD allele (RHD*01N.01) includes the entire coding sequence, intervening regions and untranslated regions. The rest of large-deletion RHD alleles reported to-date consist of single-exon deletions, such as RHD*01N.67 which includes exon 1. Samples from two donors with RhD-negative serology yielded unclear or inconclusive results when subject to confirmatory testing on RHD genotyping arrays. To determine their RHD genotypes, genomic DNA was analyzed with a combination of allele-specific PCR, long-range PCR, Sanger sequencing, and next-generation sequencing assays. Allele-specific PCR failed to detect products for RHD exons 1 to 3 in one sample and RHD exons 1 to 5 in the other. A quantitative next-generation sequencing assay confirmed deletion of exons 1 to 3 and 1 to 5 respectively, and detected the absence of an RHD gene in trans in both samples. Long-range PCR and Sanger sequencing enabled identification of the breakpoints for both alleles. Both deletions start within the 5' Rhesus box (upstream of the identity region for the 1-to-3 deletion, downstream of it for the 1-to-5 deletion), and end within introns. Resolution of unclear or inconclusive results from targeted genotyping arrays often leads to the discovery of new alleles. The 5' Rhesus box may be a hot spot for genetic recombination events, such as the large deletions described in this report.


BDNF Val66Met polymorphism modulates the effect of loneliness on white matter microstructure in young adults.
Loneliness is a common experience. Susceptibility to loneliness is a stable trait and is heritable. Previous studies have suggested that loneliness may impact regional gray matter density and brain activation to social stimuli, but its relation to white matter structure and how it may interact with genetic factors remains unclear. In this study, we investigated whether and how a common polymorphism (Val66Met) in the brain-derived neurotrophic factor gene modulated the association between loneliness and white matter microstructure in 162 young adults. The tract-based spatial statistics analyses revealed that the relationships between loneliness and white matter microstructures were significantly different between Val/Met heterozygotes and Val/Val homozygotes. Specifically, loneliness was significantly correlated with reduced fractional anisotropy and increased radial diffusivity in widespread white matter fibers within Val/Met heterozygotes. It was also significantly correlated with increased radial diffusivity in Met/Met genotypes but showed no significant association with white matter measures in Val/Val genotypes. Furthermore, the associations between loneliness and fractional anisotropy (or radial diffusivity) in Val/Met heterozygotes turned out to be global effects. These results provide evidence that loneliness may interact with the BDNF Val66Met polymorphism to shape the microstructures of white matter, and the Val/Met heterozygotes may be more susceptible to social environment.


Local delivery of CpG-B and GM-CSF induces concerted activation of effector and regulatory T cells in the human melanoma sentinel lymph node.
Impaired immune effector functions in the melanoma sentinel lymph node (SLN) may allow for early metastatic events. In an effort to determine the optimal way to strengthen immune defenses, 28 clinical stage I-II melanoma patients were randomized in a 3-arm Phase II study to receive, prior to excision and sampling of the SLN, i.d. injections of saline or low-dose CpG-B (CpG), alone or combined with GM-CSF (GM), around the melanoma excision site. We previously described the combined administration of these DC-targeting agents to result in activation and recruitment of potentially cross-presenting BDCA3(+) DCs to the SLN. In this report we describe the effects on effector and regulatory T and NK cell subsets. Local low-dose CpG administration resulted in lower CD4/CD8 ratios, Th1 skewing, increased frequencies of melanoma-specific CD8(+) T cells and possible recruitment of effector NK cells, irrespective of GM co-administration. These immune-potentiating effects were counterbalanced by increased IL-10 production by T cells and significantly higher levels of FoxP3 and CTLA4 in regulatory T cells (Tregs) with correspondingly higher suppressive activity in the SLN. Notably, CpG ± GM-administered patients showed significantly lower numbers of SLN metastases (saline: 4/9, CpG + GM: 1/9, CpG: 0/10, p = 0.04). These findings indicate that i.d. delivery of low-dose CpG ± GM potentially arms the SLN of early-stage melanoma patients against metastatic spread, but that antitumor efficacy may be further boosted by counteracting the collateral activation of Tregs.


Congenital posterior urethral perineal fistula: a case report.
A case of congenital posterior urethral perineal fistula is reported. The English literature is reviewed and anatomical findings, embryology, presenting signs and symptoms, and treatment are discussed.


A π-π 3D network of tetranuclear μ2/μ3-carbonato Dy(III) bis-pyrazolylpyridine clusters showing single molecule magnetism features.
2,6-Di(pyrazole-3-yl)pyridine, 3-bpp, forms a porous (4(9)·6(6)) π-π mediated 3D network of trigonal pyramidal [Dy(III)(4)] carbonato-bridged complexes, with hexagonal channels comprising 54% of the unit cell volume, the material displaying slow magnetisation reversal.


Cultured corneal fibroblasts as a model system for the demonstration of drug-induced mucopolysaccharidosis.
The purpose of the present investigation was to establish a cell culture system suitable for demonstrating the drug-induced lysosomal storage of sulfated glycosaminoglycans (GAGs). This is a drug side-effect which was previously studied in animals treated with the di-cationic amphiphilic compound tilorone and congeners, and which is likely to occur in humans, too. Cultured corneal fibroblasts of rats were exposed to tilorone for 72 h. They developed histochemical and cytochemical alterations indicative of mucopolysaccharidosis and resembling those occurring in vivo. The threshold drug concentration was found to be below 0.7 microM. The reversibility of the lysosomal GAG storage was low. An increase in the drug concentration to 10 microM produced additional unspecific lysosomal alterations, while the mucopolysaccharidosis-like lesions became less prominent. Concentrations of 40 microM and 80 microM caused unspecific cytoplasmic vacuolation and cell death, respectively. The present model system appears suitable for screening investigations of newly developed drugs with respect to their mucopolysaccharidosis-inducing potential and for investigating the structure-activity relationships underlying this adverse drug effect. Care should be taken not to use too high drug concentrations which cause unspecific lysosomal lesions.


Can nurses safely assess the need for endotracheal suction in short-term ventilated patients, instead of using routine techniques?
Most literature describes endotracheal suction as a hazardous procedure associated with numerous complications and proposes that it should only be performed as necessary to minimize these complications. Other authors suggest endotracheal suction only after assessment predisposes patients to a number of different complications. This article describes a controlled study to compare and contrast the differences in endotracheal suction outcomes in patients who received ritualized 2 hourly suctioning and those who received it following assessment. A group of qualified nurses in an Intensive Care Unit were taught auscultation skills to assess a patient's needs for suctioning and all the nurses received educational training regarding endotracheal suctioning. Short-term ventilated patients were allocated to receive endotracheal suctioning either when the need for it was determined by assessment only or routinely, using a standardized suctioning technique. The results demonstrated a clear increase in nurses' knowledge regarding endotracheal suctioning. The assessed group of patients demonstrated significantly better outcomes and less complications than the controlled group in relation to changes in peak airway pressures, heart rate and mean arterial pressure pre- and post-endotracheal suctioning, and the amount of secretions obtained on suctioning. Although only preliminary, these results do provide support for the view that endotracheal suction only in response to assessment is better practice for short-term ventilated patients.


Clinical application of the mirror irradiation technique in photodynamic therapy for malignant glioma.
Intraoperative photodynamic therapy (PDT) using talaporfin sodium for malignant glioma is effective both in the experimental and in the clinical setting. Because the irradiation unit is fixed to the objective lens of the operating microscope, blind spots for irradiation exist. To overcome this problem, we developed a mirror reflecting system using a modified dental mirror. The developed mirror is made of stainless steel, has a mirror-polished surface, and is rhodium coated on 1 side, which is the reflecting surface. The reflection rate was measured using He-Ne laser irradiation. The reflection intensity was measured using a laser power meter when the incident angle to the mirror was changed to 60°, 45°, and 30°, and the reflectance was calculated by the direct received light intensity from the laser. After confirming the safety of the fundamental experiment, PDT was performed with this developed mirror on 9 patients with malignant glioma (4 with recurrence and 5 newly diagnosed). The energy efficiency of the mirror was approximately 70 %, and apparent irregular reflection was not observed. Even during clinical use, apparent complications, such as irregular reflection, did not occur upon using the mirror in any of the patients. In all patients, recurrence did not occur in the site where mirror irradiation was performed, but in a deep site or a distant site to which sufficient laser irradiation did not reach. PDT using our newly developed mirror involves few instrumental changes compared with the conventional irradiation method, and is effective, safe, and inexpensive.


Single cell isolation: a way to examine network interactions.
A procedure for isolating identified, small neurons from snail ganglia is described. The technique allows a particular neuron, previously identified by morphological and electrophysiological characteristics, to be marked and then isolated from the ganglia. This procedure was developed to permit the detailed comparison of the electrical characteristics of a neuron before and after isolation from an intact system. An earlier description has appeared. The cell somata is marked intracellularly by the iontophoretic injection of Procion navy blue H3RS which visually differentiates the cell from other cells in the ganglion. The ganglion is then treated with a trypsin-haluronidase solution to soften the ganglion sheath, which is then removed. The cells are gently shaken to isolate them from the ganglion and then examined electrophysiologically. A comparison of membrane properties, such as action potential height, duration and rate of rise and decay was made before and after all treatments were applied to assess deleterious effect. An analysis of network properties, such as burst duration, number of spikes per burst and presynaptic activity was also performed after each phase of the procedure. No significant differences were noted after dye injection, enzyme treatment, and where appropriate, after isolation. An increase in input resistance and corresponding decrease in the slope of the steady state current--voltage plot (I--V plot) were observed after isolation of a cell. These were expected results of removing the 'load' (i.e. axon or electrical coupling) from the cell soma. This method may be applied to many other systems to study the effects of network interactions on the properties of a single cell and should therefore facilitate the analysis of neuronal networks as well as single cell properties.


Introducing RGBeta: a Mathematica package for the evaluation of renormalization group β -functions.
In completely generic four-dimensional gauge-Yukawa theories, the renormalization group β -functions are known to the 3-2-2 loop order in gauge, Yukawa, and quartic couplings, respectively. It does, however, remain difficult to apply these results to realistic models without the use of dedicated computer tools. We describe a procedure for extracting β -functions using the general results and introduce RGBeta, a dedicated Mathematica package for extracting the MS ¯ β -functions in broad classes of models. The package and example notebooks are available from the GitHub repository.


Rupture of the innominate artery from blunt trauma: current options for management.
Rupture of the innominate artery is the second most common intrathoracic arterial injury from blunt trauma. It is frequently accompanied by major trauma to other organs. The traditional management is expeditious surgical repair. Three patients presented to the Emergency Department after motor vehicle collisions with traumatic rupture of the innominate artery from 2001 to 2003. One patient presented with an isolated innominate artery injury. The other two patients presented with multi-system trauma. All patients underwent surgical repair; however, repair was individualized in each case. Diagnosis was obtained via arteriography in all patients after the admission chest radiographs suggested mediastinal injury. In the patient with isolated traumatic innominate artery rupture, urgent repair was performed. In the remaining two, the repair was intentionally delayed (hospital day 4 and 19) until they stabilized or recovered from other injuries or complications. In one of these patients, repair was delayed after an endovascular repair failed. In both patients who underwent delayed repair, mean arterial pressure was maintained at <70 mmHg with beta-blockade. All patients underwent repair without cardiopulmonary bypass and were monitored for adequate cerebral perfusion pressures by measuring the right carotid artery stump pressure. Successful repair was achieved in all the three patients without postoperative complications or mortality. Rupture of the innominate artery from blunt trauma is an infrequent but life-threatening injury that mandates repair. In patients with isolated injuries, prompt intervention is warranted. However, intentional delayed repair may be a practical alternative for those patients with multi-system trauma.


Tofacitinib in Patients With Psoriatic Arthritis and Metabolic Syndrome: A Post hoc Analysis of Phase 3 Studies.
Metabolic syndrome (MetS) is a cluster of concurrent risk factors for cardiovascular disease and type 2 diabetes. This post hoc analysis explored key efficacy and safety endpoints in patients with psoriatic arthritis (PsA) and MetS treated with tofacitinib. Tofacitinib 5 and 10 mg twice daily and placebo data were pooled from two Phase 3 studies (OPAL Broaden [12 months; ClinicalTrials.gov identifier NCT01877668]; OPAL Beyond [6 months; ClinicalTrials.gov identifier NCT01882439]); patients received one background conventional synthetic disease-modifying antirheumatic drug. Patients were stratified by baseline presence/absence of MetS. Efficacy and safety were reported to month 3 (tofacitinib and placebo) and 6 (tofacitinib only). Efficacy outcomes included: American College of Rheumatology (ACR)20/50/70, Health Assessment Questionnaire-Disability Index (HAQ-DI) response, Psoriasis Area Severity Index (PASI)75 response, and enthesitis/dactylitis resolution rates; and changes from baseline (Δ) in C-reactive protein, HAQ-DI, Patient's/Physician's Global Assessment of Arthritis, and patient-reported outcomes. Safety outcomes included treatment-emergent all-causality adverse events (AEs), Δ in lipid/hepatic values, and liver parameter increases. Of 710 patients, 41.4% (n = 294) had baseline MetS. All efficacy outcomes improved with both tofacitinib doses versus placebo, to month 3; tofacitinib efficacy was consistent to month 6, regardless of MetS status. MetS did not appear to affect the incidence of AEs or Δ in lipid/hepatic values with tofacitinib up to month 3 or 6. Arterial thromboembolism and myocardial infarction (adjudicated major adverse cardiovascular events) were each reported once in tofacitinib-treated patients with MetS. Regardless of baseline MetS status, tofacitinib showed greater efficacy versus placebo in patients with active PsA. The tofacitinib safety profile appeared similar in patients with versus without MetS.


Influence of prolonged static stretching on motor unit firing properties.
The purpose of this study was to examine the influence of a stretching intervention on motor control strategy of the biceps brachii muscle. Ten men performed twelve 100-s passive static stretches of the biceps brachii. Before and after the intervention, isometric strength was tested during maximal voluntary contractions (MVCs) of the elbow flexors. Subjects also performed trapezoid isometric contractions at 30% and 70% of MVC. Surface electromyographic signals from the submaximal contractions were decomposed into individual motor unit action potential trains. Linear regression analysis was used to examine the relationship between motor unit mean firing rate and recruitment threshold. The stretching intervention caused significant decreases in y-intercepts of the linear regression lines. In addition, linear slopes at both intensities remained unchanged. Despite reduced motor unit firing rates following the stretches, the motor control scheme remained unchanged.


Cambium pre-activation in beech correlates with a strong temporary increase of calcium in cambium and phloem but not in xylem cells.
Using secondary ion mass spectrometry (SIMS), calcium was imaged in cambium cells and in the adjacent secondary phloem and xylem cells during the different phases of cambium functioning in beech (Fagus sylvatica L.). At the end of the period of quiescence, immediately before the resumption of cell divisions (i.e. at the cambium pre-activation phase), a strong temporary increase of calcium concentration was observed to take place in cambium and phloem but not in xylem cells.


Using focus groups to improve the validity of cross-national survey research: a study of physician decision making.
In this article, the authors demonstrate how qualitative methods can form a foundation for quantitative research by improving instrument validity, informing the data collection process, and improving cost-effectiveness in a study of physician decision making. To test terminology, applicability, and comprehension of a quantitative questionnaire for doctors in the United States and United Kingdom, each country's researchers conducted physician focus groups with questions organized around the experiment, including (a) validity of video vignettes of actor "patients," (b) population accessibility, (c) level of remuneration, (d) appropriate endorsement figure, and (e) question comprehension. Focus group data collected during instrument development and fieldwork planning streamlined processes and achieved cost efficiencies and effectiveness for the overall study. Beyond simply adding a post hoc qualitative component to an already free-standing quantitative methodology, focus groups were used in the study formulation, where the qualitative methodology was integrated into the process of developing a valid survey instrument.


Factors affecting pediatric adherence to positive airway pressure: Patient- and caregiver-reported treatment barriers and sleep difficulties.
Adherence to positive airway pressure (PAP) treatment among children and adolescents is often suboptimal. Little is understood about modifiable determinants of PAP adherence. We evaluated whether patient and caregiver-perceived treatment barriers (across behavioral, environmental, emotional, and physical domains), as well as insomnia severity, were associated with PAP adherence among youth with sleep disordered breathing (SDB). We conducted a retrospective review of 188 patients prescribed PAP, ages 2-19 years. At the clinical visit, PAP adherence was assessed via objective download/smartcard and patients and their caregivers completed validated standardized questionnaires on barriers to PAP adherence and sleep onset and maintenance difficulties. We tested predictors of PAP adherence using linear regression. On average, patients wore their PAP 2/3 of nights for 5.3 ± 3.4 h. Patients reported more barriers overall compared to caregivers, and specifically more behavioral and emotional barriers (e.g., over a third of patients reported they just want to forget about sleep apnea). After controlling for demographic/treatment characteristics, patient-reported barriers accounted for a significant proportion of the variance in percent nights used (51%) and average nightly use (42%). Greater difficulties with sleep maintenance predicted poorer PAP adherence (percent nights and nightly duration). Study findings suggest that assessment of both patient and caregiver-perceived barriers to PAP adherence, as well as evaluating for sleep maintenance concerns, may provide important treatment targets for promoting PAP adherence among youth. Results also support the potential benefit of a multi-disciplinary team-based approach to managing SDB and promoting PAP adherence.


Water-soluble characteristics of chlorine in char derived from municipal solid wastes.
Chlorine in char derived from municipal solid waste (MSW) was characterized and quantified based on its water solubility: easily water-soluble, hardly water-soluble, and non-water-soluble chlorine. For that, a four-cycle process of water-washing, heating or carbonation were carried out. In order to confirm the characteristics of non-water-soluble chlorine, additional thermal treatment and an alkali-acid washing process were applied to washed char. It was found that a large particle size of char (0.5-1.0 mm) significantly contributed to the amount of non-water-soluble chlorine. Pulverization and HNO3-HF digestion were performed to identify a factor to interfere chlorine release from char with a large particle size. Pulverization was proven ineffective for release of non-water-soluble chlorine, whereas approximately 32% of non-water-soluble chlorine was extracted by HNO3-HF digestion. Therefore, the presence of non-water-soluble chlorine is likely to originate from its chemical property rather than simply from its physical one.


Differential expression of collateral sensitivity or resistance to cisplatin in human bladder carcinoma cell lines pre-exposed in vitro to either X-irradiation or cisplatin.
Two sublines were derived from a human bladder carcinoma continuous cell line (RT112-P), one by exposure to fractionated X-irradiation (RT112-DXR8) and the other by continuous exposure to cisplatin (RT112-CP). RT112-DXR8 cells were 1.6- to 2-fold more sensitive to cisplatin and 2 analogues, carboplatin and iproplatin, compared with the parental line, whereas RT112-CP cells were 1.6- to 2.8-fold more resistant to these agents. Uptake of 195mcisplatin was elevated 1.4-fold in RT112-DXR8 cells compared with RT112-P cells whereas uptake into RT112-CP cells was similar to that of the parental line. Binding of 195mcisplatin to DNA was similar in all 3 lines. Levels of reduced glutathione were significantly elevated in RT112-CP cells and significantly reduced in RT112-DXR8 cells compared with the parental cells. In addition, activities of glutathione reductase and glutathione peroxidase were higher in RT112-CP cells than in the parental cells whereas the activity of glutathione-S-transferase was similar in all 3 cell lines. A 2.5-fold greater induction of DNA-DNA interstrand crosslinks occurred in RT112-DXR8 cells compared with the parental line, whereas crosslinking in RT112-CP cells, whilst initially similar to that seen in RT112-P cells, was significantly elevated at later times. These findings suggest that mechanisms associated with the expression of resistance and collateral sensitivity to cisplatin may differ.


High genetic variance in life-history strategies within invasive populations by way of multiple introductions.
Biological invasions represent major threats to biodiversity as well as large-scale evolutionary experiments. Invasive populations have provided some of the best known examples of contemporary evolution [3-6], challenging the classical view that invasive species are genetically depauperate because of founder effects. Yet the origin of trait genetic variance in invasive populations largely remains a mystery, precluding a clear understanding of how evolution proceeds. In particular, despite the emerging molecular evidence that multiple introductions commonly occur in the same place, their contribution to the evolutionary potential of invasives remains unclear. Here, by using a long-term field survey, mtDNA sequences, and a large-scale quantitative genetic experiment on freshwater snails, we document how a spectacular adaptive potential for key ecological traits can be accumulated in invasive populations. We provide the first direct evidence that multiple introductions are primarily responsible for such an accumulation and that sexual reproduction amplifies this effect by generating novel trait combinations. Thus bioinvasions, destructive as they may be, are not synonyms of genetic uniformity and can be hotspots of evolutionary novelty.


Spatial-temporal distribution of whisker-evoked activity in rat somatosensory cortex and the coding of stimulus location.
Rats use their facial vibrissae ("whiskers") to locate and identify objects. To learn about the neural coding of contact between whiskers and objects, we investigated the representation of single-vibrissa deflection by populations of cortical neurons. Microelectrode arrays, arranged in a geometric 10 x 10 grid, were inserted into the thalamo-recipient layers of "barrel cortex" (the vibrissal region of somatosensory cortex) in urethane-anesthetized rats, and neuronal activity across large sets of barrel-columns was measured. Typically, 5 msec after deflection of a whisker a 0.2 mm(2) focus of activity emerged. It rapidly expanded, doubling in size by 7 msec, before retracting and disappearing 28-59 msec after stimulus onset. The total territory engaged by the stimulus ranged from 0.5 to 2.9 mm(2) (2-11 barrels). Stimulus site dictated the domain of activity. To quantify the coding of whisker location, we applied the population d' measure of discriminability. Activity patterns elicited by two whiskers were highly discriminable at the initial cortical response; peak discriminability typically occurred within 16 msec of stimulus onset. To determine how widely information about stimulus location was distributed, we measured population d' while excluding response data from the on-center electrodes of the two tested whiskers. Response patterns remained discriminable, indicating that information about stimulus location was distributed across barrel cortex. Taken together, these results show that single-whisker deflections are represented in a multicolumn region constrained by barrel cortex map topography. The nature of this coding allows information about stimulus location to be coded extremely rapidly and unambiguously by one to two spikes per neuron.


Selective use of segmental Doppler pressures and color duplex imaging in the localization of arterial occlusive disease of the lower extremity.
The purpose of this study was to compare the abilities of segmental Doppler pressures (SDP) and color duplex imaging (CDI) to localize arterial stenosis and to assess the ability of CDI to accurately categorize the severity of disease. We analyzed 134 patients (268 limbs) who underwent all three tests; SDP, CDI, and arteriograms. Results of SDP and CDI were examined to determine their accuracy in localizing high grade (greater than 50%) stenosis at three levels; aortoiliac-common femoral artery (level I), superficial femoral artery (SFA; level II), and popliteal artery (level III). The sensitivity, specificity, positive and negative predictive values, and overall accuracy for SDP and CDI were as follows: level I, 63%, 88%, 81%, 75%, and 77%; 93%, 99%, 98%, 95%, and 96%, respectively (p < 0.01); level II, 51%, 99%, 99%, 57%, and 70%; 94%, 98%, 99%, 92%, and 96%, respectively (p < 0.01); level III, 55%, 92%, 60%, 90%, and 85%; 78%, 100%, 97%, 95%, and 95%, respectively (p < 0.01). Exact agreement was noted between the CDI and arteriogram in regard to the severity of disease in 88% of the limbs (1170 segments). The presence of SFA disease in patients with level I disease or aortoiliac-common femoral artery disease in patients with level II disease did not significantly alter the ability of SDP to localize the disease. The presence of diabetes significantly affected the accuracy of SDP in localizing SFA and popliteal artery stenosis. An analysis of SDP's ability to detect any segment as abnormal, as confirmed by arteriogram, revealed a sensitivity of 88%, specificity of 82%, positive predictive value of 96%, negative predictive value of 60%, and overall accuracy of 87%. The average cost was $149 for an SDP and $472 for a CDI. CDI is superior to SDP in localizing arterial stenosis at all levels. However, because SDP is cheaper it can be used initially if no surgical or endovascular intervention is planned.


Mitotic asynchrony of multinucleate cells in tissue culture.
A high degree of mitotic asynchrony is reported for spontaneously arising multinucleate cells of HeLa and Pt-K1, tissue culture cell lines. Neither nuclear number, nor nuclear size nor the presence or absence of nucleoli, could be directly related to the asynchronous behaviour of the cells. Suboptimal levels of nutrients led to a higher frequency of asynchrony. A partial compartmentation of the cytoplasm could be detected in some of the multinucleate cells. The compartmentation of the cytoplasm may lead to an uneven distribution of inducer and non-inducer metabolites. All these factors together may be responsible for the high degree of mitotic asynchrony.


Diaphragmatic repair of two cases of hepatic hydrothorax using video-assisted thoracoscopic surgery.
Hepatic hydrothorax is defined as the presence of a significant pleural effusion that develops in a patient with cirrhosis of the liver who does not have underlying cardiac or pulmonary disease. There are few published case reports dealing with hepatic hydrothorax treated surgically because patients with hepatic hydrothorax have end-stage liver disease. Recently, we treated two patients with refractory hepatic hydrothorax by directly suturing the diaphragmatic defects during video-assisted thoracoscopic surgery (VATS). During surgery, the diaphragmatic defects were identified using abdominal insufflation of saline with indocyanine green or carbon dioxide. After suture closure using fibrin glue, both right pleural effusions were improved. The patients' postoperative courses were uneventful, and they did not require a drainage tube when they were discharged.


Environmental, parental and adaptive variation in egg size of Tengmalm's owls under fluctuating food conditions.
We studied egg size variation of Tengmalm's owls in western Finland during 1981-1990. The owls fed on voles whose population fluctuated in a predictable manner: low (1981, 1984, 1987, 1990), increase (1982, 1985, 1988) and peak (1983, 1986, 1986) phases of the cycle occurred every third year. Eggs were largest in the increase phase of the vole cycle, even though that voles were more abundant and egg-laying started earlier in the peak phase than in the increase phase. This suggests that owls invest mostly in egg size when vole abundance increases along with survival chances of offspring. Territory quality and female age had no effects on egg size, but egg size decreased with laying data in the increase phase of the vole cycle. Egg size was significantly positively related to the male age in the increase phase, but the opposite relationship was significant in the peak phase of the vole cycle. The partners of adult males also decreased their egg volume from the increase to the peak phase, whereas the partners of yearling males produced their largest eggs in the peak phase of the vole cycle. This suggests the importance of experience in prevailing food fluctuations. Possibly male Tengmalm's owls can adjust the intensity of courtship feeding not only in relation to the food abundance on their territories at the time of egg laying, but also to the survival prospects of their offspring. Phenotypic plasticity seems to play a substantial role, as the egg size repeatabilities of individual females and partners of individual males were low. Obviously, under cyclic food conditions, predictability and inter-generational trade-offs are important to life history traits.


Surfactants and atherogenesis.
In previous publications (1,2) the hypothesis was put forward that atheroma is caused by some pathogen or metabolic fault which impairs the transportability of cholesterol in the plasma. The lipoproteins containing the faulty metabolites are assumed to be incapable of traversing the capillary endothelium and continue to circulate uselessly in the blood stream, possibly giving rise to hypercholesterolaemia, until captured by lipophages which, if they can successfully complete their journey, void them into the gall bladder. The present paper takes the argument a step further by pointing out that the types of substances most likely to cause the described impairment are surfactants. A surfactant finding its way into the plasma could separate cholesterol from its carrier protein and itself become its carrier. The complex would still be kept in suspension in the plasma, but unable to cross biological barriers like the capillary endothelium. An important argument in favour of the hypothesis is that it can offer an explanation of the long-standing medical mystery of the connection between atheroma and the hardness or softness of the water supply. Infant deaths from coronary occlusion present a similar enigma. The paper points out that surfactants can conceivably find their way into infants' feeding bottles.


Immunogenetic determinants and prediction of IDDM in French schoolchildren.
Islet cell antibodies (ICAs) are predictive markers of the disease in first-degree relatives of patients with insulin-dependent diabetes mellitus (IDDM). The large majority of newly diagnosed cases, however, will develop in children with no family history of diabetes. In France, the risk for development of IDDM up to the age of 20 years is 60 times higher in first-degree relatives than in the general population. The aim of this study was to test whether data collected in the first-degree relatives of IDDM patients could be transferred to children for the prediction of overt diabetes. A large population-based cohort of French school-aged children (n = 13,380; ages 6-17 years) were screened for ICAs, and results were compared with those of 1,185 first-degree relatives of IDDM patients. ICA prevalence rates were significantly different in the two populations (5.5% vs. 1.5%; P < 0.0001), with a significantly higher proportion of high ICA titers in first-degree relatives (37%) than in schoolchildren (14%) (P = 0.0005). ICA titers remained remarkably stable in children over 4 years. Insulin autoantibodies (IAAs) were found in 3.4 and 15.4% of ICA+ children and first-degree relatives, respectively. Susceptibility alleles at the human leukocyte antigen (HLA)-DQB1 locus were observed significantly more frequently in children in whom ICA titers > or = 20 Juvenile Diabetes Foundation units (JDF U) were found on two separate occasions (67%) than in ICA- children (52%) (P = 0.05). Five subjects developed overt diabetes during follow-up. ICA titers of > 20 JDF U were found in all of them on the first sample and at follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)


Electrophysiological investigation of human embryonic stem cell derived neurospheres using a novel spike detection algorithm.
Microelectrode array (MEA) technology in combination with three-dimensional (3D) neuronal cell models derived from human embryonic stem cells (hESC) provide an excellent tool for neurotoxicity screening. Yet, there are significant challenges in terms of data processing and analysis, since neuronal signals have very small amplitudes and the 3D structure enhances the level of background noise. Thus, neuronal signal analysis requires the application of highly sophisticated algorithms. In this study, we present a new approach optimized for the detection of spikes recorded from 3D neurospheres (NS) with a very low signal-to-noise ratio. This was achieved by extending simple threshold-based spike detection utilizing a highly sensitive algorithm named SWTTEO. This analysis procedure was applied to data obtained from hESC-derived NS grown on MEA chips. Specifically, we examined changes in the activity pattern occurring within the first ten days of electrical activity. We further analyzed the response of NS to the GABA receptor antagonist bicuculline. With this new algorithm method we obtained more reliable results compared to the simple threshold-based spike detection.


Analysis of N-acetyl-4-O-acetylneuraminic-acid-containing N-linked carbohydrate chains released by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. Application to the structure determination of the carbohydrate chains of equine fibrinogen.
The carbohydrate chains of equine fibrinogen were enzymatically released by peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F. The oligosaccharides obtained were fractionated by a combination of FPLC and HPLC and analyzed by 500-MHz 1H-NMR spectroscopy. Four monosialo and four disialo diantennary N-acetyllactosamine type of carbohydrate chains occur: (formula; see text)


Structural constraints for the Crh protein from solid-state NMR experiments.
We demonstrate that short, medium and long-range constraints can be extracted from proton mediated, rare-spin detected correlation solid-state NMR experiments for the microcrystalline 10.4 x 2 kDa dimeric model protein Crh. Magnetization build-up curves from cross signals in NHHC and CHHC spectra deliver detailed information on side chain conformers and secondary structure for interactions between spin pairs. A large number of medium and long-range correlations can be observed in the spectra, and an analysis of the resolved signals reveals that the constraints cover the entire sequence, also including inter-monomer contacts between the two molecules forming the domain-swapped Crh dimer. Dynamic behavior is shown to have an impact on cross signals intensities, as indicated for mobile residues or regions by contacts predicted from the crystal structure, but absent in the spectra. Our work validates strategies involving proton distance measurements for large and complex proteins as the Crh dimer, and confirms the magnetization transfer properties previously described for small molecules in solid protein samples.