Mitochondrial DNA analysis efficiently contributes to the identification of metastatic contralateral breast cancers.
In daily practice, a contralateral breast cancer (CBC) is usually considered as a new independent tumor despite the indications of several studies showing that the second neoplasia may be a metastatic spread of the primary tumor. Recognition of clonal masses in the context of multiple synchronous or metachronous tumors is crucial for correct prognosis, therapeutic choice, and patient management. Mitochondrial DNA (mtDNA) sequencing shows high informative potential in the diagnosis of synchronous neoplasms, based on the fact that somatic mtDNA mutations are non-recurrent events, whereas tumors sharing them have a common origin. We here applied this technique to reveal clonality of the CBC with respect to the first tumor. We analyzed 30 sample pairs of primary breast cancers and synchronous or metachronous CBCs with detailed clinical information available and compared standard clinico-pathological criteria with mtDNA sequencing to reveal the metastatic nature of CBCs. MtDNA analysis was informative in 23% of the cases, for which it confirmed a clonal origin of the second tumor. In addition, it allowed to solve two ambiguous cases where histopathological criteria had failed to be conclusive and to suggest a clonal origin for two additional cases that had been classified as independent by pathologists. Overall, the mtDNA-based classification showed a more accurate predictive power than standard histopathology in identifying cases of metastatic rather than bilateral breast cancers in our cohort, suggesting that mtDNA sequencing may be a more precise and easy-to-use method to be introduced in daily routine to support and improve histopathological diagnoses.


Effect of coil packing proximal to the dilated segment on postoperative medullary infarction and prognosis following internal trapping for ruptured vertebral artery dissection.
Medullary infarction is an important complication of internal trapping for vertebral artery dissection. This study investigated risk factors for medullary infarction following internal trapping of ruptured vertebral artery dissection. We retrospectively studied 26 patients with ruptured vertebral artery dissection who underwent endovascular treatment and postoperative magnetic resonance imaging between April 2001 and March 2013. Clinical and radiological findings were analyzed to identify factors associated with postoperative medullary infarction. Ten of the 26 patients (38%) showed postoperative lateral medullary infarction on magnetic resonance imaging. Multivariate logistic regression analysis revealed that medullary infarction was independently associated with poor clinical outcome (odds ratio (OR) 17.01; 95% confidence interval (CI) 1.68-436.81; p=0.032). Univariate analysis identified vertebral artery dissection on the right side and longer length of the entire trapped area as risk factors for postoperative medullary infarction. When the trapped area was divided into three segments (dilated, distal, and proximal segments), proximal segment length, but not dilated segment length, was significantly associated with medullary infarction (OR 1.55 for a 1-mm increase in proximal segment length; 95% CI 1.15-2.63; p=0.027). Receiver operating characteristic analysis showed that proximal segment length offered a good predictor of the risk of postoperative medullary infarction, with a cut-off value of 5.8 mm (sensitivity 100%; specificity 82.3%). Longer length of the trapped area, specifically the segment proximal to the dilated portion, is associated with a higher incidence of medullary infarction following internal trapping, indicating that this complication may be avoidable.


Competitive interaction of the OxyR DNA-binding protein and the Dam methylase at the antigen 43 gene regulatory region in Escherichia coli.
The antigen 43 surface protein of Escherichia coli is expressed in a phase-variable manner by a mechanism involving alternative activation and repression of transcription of the agn43 gene. The repressor is the OxyR DNA-binding protein, and its binding site was found to be located downstream of the agn43 transcription start site in a region of DNA that encompasses three 5'-GATC-3' sequences that are subject to Dam-mediated DNA methylation. It has been suggested previously that the phase-variable expression of antigen 43 results from a competition between Dam methylase and the OxyR repressor for these sites. The 5'-GATC-3' sequences were inactivated for methylation by site-directed mutagenesis, and all possible combinations of inactive and active sites were assessed for effects on phase-variable expression of the agn43 gene. Inactivation of any 5'-GATC-3' site individually had no effect; at least two sites had to be inactivated to disrupt the normal pattern of expression. Studies of OxyR interaction with agn43 DNA showed that methylation of any two 5'-GATC-3' sites was necessary and sufficient to block binding of the repressor. It was also found that the adenines of the second and third 5'-GATC-3' sites are required for OxyR binding, demonstrating that the sites for Dam methylation and for repressor binding are intimately associated. This is consistent with a competition model in which Dam and OxyR share a preference for specific DNA sequences in the regulatory region of the agn43 gene.


Exploring recycled agricultural wastes for high-rate removal of nitrogen in wastewater: Emphasizing on the investigation of the inner driving force and comparison with conventional liquid carbon sources.
In this study, four typical recycled agricultural wastes (AWs), corn cob, wheat straw, sawdust and walnut shells (named AW1, AW2, AW3 and AW4, respectively), were selected as external solid carbon sources to enhance the removal of nitrogen in wastewater, and specifically, the driving mechanism was thoroughly investigated. The leaching experiments showed that the dissolved organic carbon (DOC) release capacity followed the order of AW1>AW2>AW3>AW4, ranging from 6.21 to 31.92 mg/g. DOC released from AWs mainly consisted of protein-like substances, fulvic acid-like substances and humic-like substances. AW1 and AW2 achieved comparable NOx--N removal performance with a liquid carbon source of sodium acetate (SA) during the long-term denitrification experiments (>94.2%) but not for the other two AWs (only 16.8%-38.1%). Denitrification performance relied on DOC released from AWs at the beginning, while the enrichment of the functional CAZymes (including glycoside hydrolase and carbohydrate esterase) involved in cellulose and hemicellulose decomposition of AWs and functional genes (GAPDH, gap 2, PK, etc.) related to glycolysis were the inner driving force, which guaranteed the continuous supply of electron donors for denitrification. The relatively high abundances of napAB, narGHI, nirKS, norBC and nosZ, which encode nitrate reductase, nitrite reductase, NO reductase and N2O reductase, assured the better denitrification performance in the SA, AW1 and AW2 groups. In addition to denitrification-related functional genes, the relative abundances of nirBD and nrfAH associated with dissimilatory nitrate reduction were much higher in AW1 and AW2 groups than in SA group, implying that the nitrogen removal mechanism should be different in liquid carbon source and AW-based solid carbon source systems. In addition, GLU, gltBD and glnA, which participate in ammonia assimilation were the highest in the AW2 group, resulting in a large amount of organic nitrogen accumulation (peak concentration of approximately 24.5 mg/L), and this finally ruled it out as an alternative external carbon source. The abovementioned microbial mechanism was verified based on the correlation analysis of nutrient removal and functional genes combined with host bacterial analysis. Our study can provide valuable information for understanding the mechanism of using AWs as alternative external carbon sources to promote the removal of nitrogen in wastewater.


Rare genetic causes of complex kidney and urological diseases.
Although often considered a single-entity, chronic kidney disease (CKD) comprises many pathophysiologically distinct disorders that result in persistently abnormal kidney structure and/or function, and encompass both monogenic and polygenic aetiologies. Rare inherited forms of CKD frequently span diverse phenotypes, reflecting genetic phenomena including pleiotropy, incomplete penetrance and variable expressivity. Use of chromosomal microarray and massively parallel sequencing technologies has revealed that genomic disorders and monogenic aetiologies contribute meaningfully to seemingly complex forms of CKD across different clinically defined subgroups and are characterized by high genetic and phenotypic heterogeneity. Investigations of prevalent genomic disorders in CKD have integrated genetic, bioinformatic and functional studies to pinpoint the genetic drivers underlying their renal and extra-renal manifestations, revealing both monogenic and polygenic mechanisms. Similarly, massively parallel sequencing-based analyses have identified gene- and allele-level variation that contribute to the clinically diverse phenotypes observed for many monogenic forms of nephropathy. Genome-wide sequencing studies suggest that dual genetic diagnoses are found in at least 5% of patients in whom a genetic cause of disease is identified, highlighting the fact that complex phenotypes can also arise from multilocus variation. A multifaceted approach that incorporates genetic and phenotypic data from large, diverse cohorts will help to elucidate the complex relationships between genotype and phenotype for different forms of CKD, supporting personalized medicine for individuals with kidney disease.


Effect of shape and coating of a subretinal prosthesis on its integration with the retina.
Retinal stimulation with high spatial resolution requires close proximity of electrodes to target cells. This study examines the effects of material coatings and 3-dimensional geometries of subretinal prostheses on their integration with the retina. A trans-scleral implantation technique was developed to place microfabricated structures in the subretinal space of RCS rats. The effect of three coatings (silicon oxide, iridium oxide and parylene) and three geometries (flat, pillars and chambers) on the retinal integration was compared using passive implants. Retinal morphology was evaluated histologically 6 weeks after implantation. For 3-dimensional implants the retinal cell phenotype was also evaluated using Computational Molecular Phenotyping. Flat implants coated with parylene and iridium oxide were generally well tolerated in the subretinal space, inducing only a mild gliotic response. However, silicon-oxide coatings induced the formation of a significant fibrotic seal around the implants. Glial proliferation was observed at the base of the pillar electrode arrays and inside the chambers. The non-traumatic penetration of pillar tips into the retina provided uniform and stable proximity to the inner nuclear layer. Retinal cells migrated into chambers with apertures larger than 10 mum. Both pillars and chambers achieved better proximity to the inner retinal cells than flat implants. However, isolation of retinal cells inside the chamber arrays is likely to affect their long-term viability. Pillars demonstrated minimal alteration of the inner retinal architecture, and thus appear to be the most promising approach for maintaining close proximity between the retinal prosthetic electrodes and target neurons.


Elderly patient with acute, left lower abdominal pain: perforated jejunal diverticulitis (2010:7b).
An elderly patient with acute, left, lower abdominal pain is described, for whom the diagnosis of perforated jejunal diverticulitis was established by computed tomography (CT). The presence of a jejunal segmental inflammatory process, with or without abscess or perforation, in the setting of jejunal diverticulosis, is very suggestive of jejunal diverticulitis.


Simvastatin, but Not Atorvastatin, Is Associated with Higher Peak Rivaroxaban Serum Levels and Bleeding: an Asian Cohort Study from Singapore.
This study attempts to identify predictors associated with bleeding and stroke and systemic embolism (SSE) in Singaporean Asians taking rivaroxaban and apixaban. A total of 134 Singaporean patients on either rivaroxaban or apixaban for non-valvular atrial fibrillation were included for this study. Baseline characteristics were recorded at recruitment while bleeding and SSE events were recorded during a 1-year follow-up. Peak and trough drug plasma concentrations were collected based on the dosing interval and pharmacokinetics of the drugs and quantified using high performance liquid chromatography. Characteristics of patients with or without bleeds were compared using relevant statistical tests. Multivariable regression that included covariates with p < 0.1 from an initial univariable regression was performed to analyse predictors that resulted in higher risk of bleeding in patients. Median creatinine clearance (CrCl) was significantly lower in patients on rivaroxaban who experienced bleeds as compared to patients who did not experience bleeds (61.5 vs 70.8 mL/min, p = 0.047), while concomitant simvastatin use was found to be independently associated with a sixfold increased risk of bleeding (adjusted OR = 6.14 (95% CI: 1.18-31.97), p = 0.031) for rivaroxaban after controlling for body mass index, CrCl and having experienced a previous SSE. Our findings suggest that concomitant use of simvastatin with rivaroxaban may be associated with bleeding events in an Asian cohort. Further studies using physiologically based pharmacokinetic modelling are required to investigate the drug-drug interactions between these drugs.


Hazard report. Mismatched electrical requirements between heated-wire breathing circuits and heated humidifiers can jeopardize patients.
Just because heated-wire breathing circuits and heated humidifiers are physically compatible, it doesn't necessarily mean they're electrically compatible. If electrical requirements are not matched, the heated wire may overheat, potentially resulting in melting or ignition of the circuit and injury to the patient. Facilities should ensure that processes are in place to verify electrical compatibility.


Effects of 6,6-difluorocholestanol and 7,7-difluorocholestanol on hepatic enzymes of cholesterol metabolism.
The effects of 6,6-difluorocholestanol and 7,7-difluorocholestanol on enzymes of hepatic liver cholesterol were examined. Neither compound affected the activity of 3-hydroxy-3-methylglutaryl-CoA reductase. 7,7-Diffluorocholestanol had no effect on the activity of acyl-CoA: cholesterol acyltransferase or cholesterol 7 alpha-hydroxylase. However, 6,6-difluorocholestanol was a competitive substrate for cholesterol in the esterification of cholesterol catalysed by the acyltransferase. 6,6-Difluorocholestanol also inhibited hydroxylation of cholesterol by cholesterol 7 alpha-hydroxylase but was not itself a substrate for this enzyme. These results show that substitutents in ring B of the sterol can have a significant effect on the binding of the sterol to enzymes and to the catalytic mechanism if the substituent is close to the groups in the molecule that participate.


High-Burden Premature Atrial Contractions Predict New-Onset Atrial Fibrillation After Surgical Septal Myectomy.
Although increased premature atrial contractions (PACs) reportedly predict atrial fibrillation (AF) in both general and specific (e.g., patients with stroke) populations, early postoperative AF (POAF) risk in patients with increased PAC burden who require cardiac surgery remains unclear. We examined the correlation between different preoperative PAC burdens and POAF in patients with obstructive hypertrophic cardiomyopathy (OHCM) who underwent surgical treatment. We analyzed 304 consecutively admitted patients with OHCM without previous AF who underwent isolated septal myectomy between January 2015 and December 2018. All patients underwent preoperative 24-hour Holter electrocardiogram monitoring. PACs were present in 259 patients (85.20%) and absent in 45 patients (14.80%). According to the cut-off PAC number of 100 beats/24 hours, there were 211 patients (69.41%) with low-burden PACs and 48 patients (15.79%) with high-burden PACs. AF after septal myectomy occurred in 73 patients, which consisted of 3/45 in the non-PAC group (6.67%), 47/211 in the low-PAC-burden group (22.27%), and 23/48 in the high PAC burden group (47.92%). POAF incidence was higher in both low- and high-burden patients than in patients without PAC (p <0.01). Multivariate logistic regression analyses demonstrated that high-burden PACs (p = 0.02) and age (p <0.01) but not low-burden PACs (p = 0.22) independently predicted POAF in patients with OHCM. The area under the receiver operating characteristic curve for preoperative PACs was 0.72 (95% confidence interval 0.66 to 0.79, p <0.01, sensitivity: 68.49%, specificity: 69.26%). In conclusion, POAF incidence was significantly higher in patients with preoperative high-burden PACs and can predict POAF in patients with OHCM.


ABO incompatibility is associated with increased non-relapse and GVHD related mortality in patients with malignancies treated with a reduced intensity regimen: a single center experience of 221 patients.
The effect of ABO-incompatibility on transplantation outcome remains a controversial issue, with many of the reported studies showing conflicting results. In this study, we evaluate: the association between ABO-incompatibility and myeloid engraftment; the incidence and severity of acute and chronic graft-versus-host disease (GVHD); non-relapse mortality (NRM); GVHD-associated mortality, relapse and overall survival (OS). Our study includes 221 patients with malignant diseases treated in the same institution with the same reduced intensity regimen. Other variables known to affect the transplantation outcome such as age, disease, disease risk, and donor characteristics were well-balanced between ABO-matched and ABO-mismatched transplants. Analysis of our data shows increased incidence of NRM during the first months after transplantation in the groups of patients with major and minor ABO-incompatibility. Although neither incidence nor severity of GVHD differed significantly among the different groups, we found increased mortality associated with GVHD in the major ABO-incompatible groups. Long-term OS and relapse rate were not different, although we observed a trend for decreased OS during the first year post transplantation in the group of patients with major ABO-incompatibility. Our study showed that ABO-incompatibility has an adverse impact on the transplantation outcome.


Oxygen-supplemented transepithelial-accelerated corneal crosslinking with pulsed irradiation for progressive keratoconus: 1 year outcomes.
To investigate the effects of combining oxygen supplementation with enhanced UV-A light and increased riboflavin permeability in improving the efficacy of epithelium-on crosslinking (epi-on CXL). Private eye clinic in Brisbane, Queensland, Australia. Retrospective single-center nonrandomized uncontrolled longitudinal cohort case series. Transepithelial CXL was performed on keratoconic eyes. Applications of an oxygen goggle and pulsed UV-A irradiation (1 second on, 1 second off) were used to enhance oxygen kinetics during epi-on CXL. Additional procedural modifications included the use of benzalkonium chloride and high UV-A irradiance level (30 mW/cm 2 ) to improve the stromal bioavailability of riboflavin and UV-A. The main efficacy outcomes were the changes in mean corrected distance visual acuity (CDVA) and safety over 12 months. Additional refractive and keratometry (K) outcomes were also observed. 53 eyes (38 patients) were included in this study. 12 months postoperatively, mean CDVA improved from a mean of 0.18 ± 0.2 at baseline to 0.07 ± 0.1 logMAR ( P < .0001). No statistically significant change was observed in maximum K (Kmax) and mean K, which were respectively 51.7 ± 5.8 diopters (D) and 46.4 ± 3.85 D at baseline and 51.2 ± 5.7 D ( P = .152) and 46.0 ± 3.84 D ( P = .06) 12 months postoperatively. Only 3 eyes experienced an increase of more than 2 D in Kmax; however, none of these eyes experienced a CDVA loss. There were no reported infections, corneal scarring, or other severe adverse effects. Performing supplemental oxygen epi-on CXL with accelerated, pulsed UV-A irradiation in conjunction with riboflavin permeability enhancers resulted in improved CDVA ( P < .0001) and stable keratometry up to 12 months postoperatively with a good safety profile.


Virtual reality for acute pain in outpatient hysteroscopy: a randomised controlled trial.
To evaluate the effectiveness of virtual reality as a distraction technique in the management of acute pain and anxiety during outpatient hysteroscopy. Parallel group, prospective randomised controlled trial. UK University Hospital. Forty consenting, eligible women were randomised to virtual reality intervention (immersive video content as a distraction method) or standard care during outpatient hysteroscopy from August to October 2018. Pain and anxiety outcomes were measured as a numeric rating score (scale 0-10). Compared with standard care, women with virtual reality intervention experienced less average pain (score 6.0 versus 3.7, mean difference 2.3, 95% CI 0.61-3.99, P = 0.009) and anxiety (score 5.45 versus 3.3, mean difference 2.15, 95% CI 0.38-3.92, P = 0.02). Virtual reality was effective in reducing pain and anxiety during outpatient hysteroscopy in a mixed-methods randomised control trial. Its wide potential role in ambulatory gynaecological procedures needs further evaluation. Virtual reality can be used as a part of a multimodal strategy to reduce acute pain and anxiety in patients undergoing outpatient hysteroscopy.


Scanning electron microscopic evaluation of ultrasonic debridement comparing sodium hypochlorite and Bardac-22.
This study compared in vitro the debridement ability of a 3% sodium hypochlorite with a new quaternary ammonium derivative, a 0.5% Bardac-22 solution, in the apical third of freshly extracted teeth with straight root canals. Root canals were instrumented sequentially from size 10 to size 35 using alternatively hand and ultrasonic files. When the hand file was loose in the canal, the ultrasonic instrument of the same size was operated at working length for 30 s, delivering 15 ml of the selected solution. Both solutions were able to flush out pulpal debris from the canal space. At the apical end of the preparation, sodium hypochlorite left a thicker smear layer than Bardac-22 did. The quaternary ammonium derivative easily dissolved the inorganic portion of the smear layer, but did not dissolve proteins as well as sodium hypochlorite.


Report of terbinafine resistant Trichophyton spp. in Italy: Clinical presentations, molecular identification, antifungal susceptibility testing and mutations in the squalene epoxidase gene.
Numerous reports of resistance to terbinafine in Trichophyton spp. from all over the world are arousing justified attention and concern. Point mutations in the gene that encodes the squalene epoxidase (SQLE) enzyme are responsible for these therapeutic resistances. Primary objective of the study was to describe first isolates of Trichophyton spp. resistant to terbinafine among the patients treated between September 2019 and June 2022 at the Dermatology Units of Ospedale Maggiore Policlinico and San Bortolo Hospital. Secondary objective was to study the resistance mechanism. Patients with confirmed Trichophyton spp. infection has been treated with systemic and topical terbinafine. Patients were then re-evaluated 12 weeks after the therapy. Patients with incomplete or absent response to terbinafine underwent a new skin scraping for direct mycological examination, new identification of dermatophyte species from culture and MALDI-TOF, molecular species identification, antifungal susceptibility testing and molecular analysis of SQLE gene. We identified five patients without clinical response to treatment with terbinafine. The DNA sequencing of the ITS region identified one Trichophyton rubrum and four Trichophyton indotineae. The T. rubrum strain showed minimum inhibitory concentration (MIC) (90% growth inhibition) of 4 mg/L for terbinafine. The four T. indotineae strains showed a MICs range of 0.25-4 mg/L for terbinafine. The analysis of the SQLE gene in the T. rubrum strain showed a nucleotide substitution generating a missense mutation (L393F). The SQLE gene sequencing in the T. indotineae strains showed a nucleotide substitution generating a missense mutation (F397L) in two strains, a nucleotide substitution L393S in one strain and a nucleotide substitution F415C in another strain. We report the first cases of terbinafine-resistant Trichophyton isolates in the Italian population. Solid antifungal management programs will be needed to promote more responsible use of antimycotics and preserve their therapeutic efficacy to control antifungal resistance.


Quantitative autoradiography of angiotensin II receptors in the rat solitary-vagal area: effects of nodose ganglionectomy or sinoaortic denervation.
The experiments reported here were designed to examine whether angiotensin II (AII) receptors in the rat solitary-vagal area (SVA) are associated with the neuronal components of the baroreceptor reflex. AII receptors were characterized both in membrane preparations from the rat brainstem and by in vitro autoradiography using the radiolabeled AII antagonist [125I]Sar1,Ile8-AII([ 125I]SI-AII). Saturation analysis of [125I]SI-AII binding to membrane preparations from rat brainstem indicated binding to two high affinity sites (Kd1 0.32 nM and Bmax1 5.10 fmol/mg protein, Kd2 0.99 nM and Bmax2 7.94 fmol/mg protein). The rank order competition by unlabeled angiotensin peptides (SI-AII greater than AII greater than AIII greater than AI) in both membrane preparations and by quantitative autoradiography was consistent with the labeling of the brain AII receptor. Autoradiography of the [125I]SI-AII binding in sections through the SVA revealed that the nucleus tractus solitarius (NTS) and the dorsal motor nucleus of the vagus (DMV) were heavily labeled. Bilateral sinoartic denervation, which disrupts primary baroreceptor afferents, resulted in a small decrease in [125I]SI-AII binding in the rostral and intermediate NTS and DMV. Unilateral nodose ganglionectomy, which disrupts completely the vagal afferent input to the NTS and produces retrograde degeneration of the vagal efferent neurons in the DMV, resulted in a marked decrease in [125I]SI-AII binding at all levels of the ipsilateral NTS and 56% decrease within the ipsilateral DMV. These results indicate that AII receptors within the SVA are distributed heterogeneously, with a large portion associated with vagal afferent fibers in the NTS and vagal efferent neurons of the DMV, and a small but significant portion associated with baroreceptor afferents. The majority of AII receptors in the NTS, however, were not affected by these surgical interventions and therefore appear to be located on intrinsic interneurons or non-vagal afferents in the NTS.


Papillary variant of squamous cell carcinoma arising on the gingiva: 61 cases reported from within a larger series of gingival squamous cell carcinoma.
Papillary squamous cell carcinoma (PSCCA) is a rarely occurring variant of squamous cell carcinoma (SCCA) with distinctive exophytic and papillary features and a more favorable prognosis than conventional SCCA. The larynx is the most commonly affected site in the head and neck. The oral cavity, oropharynx, sinonasal tract, and nasopharynx are also affected. Within the oral cavity cases have been reported on the alveolar ridge, oral mucosa, floor of the mouth, ventral tongue, and rarely other areas. We identified 61 cases of gingival PSCCA within the parameters of a larger study of 519 cases of gingival SCCA. We evaluated the clinical and histologic features of these lesions. The average age of the PSCCA patient was 74 years, with a very slight male predominance of 1.2:1. The mandible was affected nearly twice as often (64 %, n = 39) as the maxilla (35 %, n = 21, and 1 % of cases unspecified), and the most common location by far was the mandibular posterior region (52 %, n = 32). Most lesions were reportedly present over 2 months in duration (48 %, n = 29) prior to biopsy but a significant amount of clinicians were unsure of the duration of the lesion as well (36 %, n = 22). Only 10 cases (16 %) were reportedly present less than 2 months. The most common clinical presentation was that of an erythematous or mixed white and red exophytic mass (74 %, n = 45). 62 % (n = 38) of submitting clinicians considered a malignant or premalignant lesion in their differential diagnosis, but other clinical impressions included papillomas, reactive gingival lesions, and fungal infections. Histologically, 88 % (n = 52 of 59 cases graded) of the lesions were either well or moderately-well differentiated. PSCCA is a rare subtype of SCCA which has been reported infrequently involving the gingiva or alveolar ridges but should be considered by clinicians for the differential diagnosis of papillary gingival masses.


Chronopharmacological effects on nicotine repeated administration on heart rate, body temperature and locomotor activity circadian rhythms in rats.
The aim of this study was to compare morning and evening repeated nicotine administration on the circadian rhythms of heart rate (H), body temperature (T) and locomotor activity (A) in unrestrained rats by using implanted radio-telemetry transmitters. The study was divided into three 7-day periods: a control period (P1), a treatment period (P2) and a recovery period (P3). During P2, four rats received nicotine (1mg.kg(-1)) subcutaneously at 09.00 h and four rats received nicotine in the same conditions at 21.00 h. For P1, P2 and P3, a power spectrum analysis was applied in order to determine the dominant period of rhythmicity. If H, T and A circadian rhythms were detected, the characteristics of these rhythms were determined by cosinor analysis, expressed as means+/-SEM and compared by ANOVA. Our results indicated: (1) a lack of detection of A circadian rhythm during P2 for the morning group while H and T circadian rhythms were detected for the morning and evening group whatever the period. (2) alterations of mesors, amplitudes and acrophases of H and T circadian rhythms for the morning and evening group during P2 and alterations of mesor, amplitude and acrophase of A circadian rhythm for the evening group. Furthermore these alterations were significantly different for the morning and evening group during P2. These results showed that the time of administration of nicotine differently affect H, T and A rhythms. The authors suggest that these effects can be mediated by central cholinergic and/or monoaminergic mechanisms.


Evaluation of the automated leukocyte differential count in emergency department patients.
This study compares the results of the leukocyte three-part differential count as determined by the Coulter S-Plus IV in 104 consecutive patient samples from the emergency department with results obtained by conventional visual differential. A high rate (40%) of instrument rejection was found, reflecting the high prevalence of disease and hematologic abnormalities in the patient population. No clinically significant abnormality went undetected, demonstrating that the automated leukocyte three-part differential is effective as a screening test in the emergency department patient population.


Constraint of musculoskeletal tissue and path planning of robot-assisted fracture reduction with collision avoidance.
For the robot-assisted fracture reduction, due to the complex fracture musculoskeletal environment, it is necessary to consider the influence of soft tissue traction on preoperative reduction path planning. An improved 3D A* algorithm is adopted to plan the fracture reduction path. The distal fragment point clouds are updated to avoid the collision, and the end point coordinates of the muscles are updated to calculate muscular lengths during the path search. 3D reduction path of long-bone fracture is planned, effectively avoiding the fracture fragments collision and ensuring the length of the corresponding muscle is always less than the allowable maximum muscle length after elongation. The proposed method can effectively avoid the collision between the distal fragment and the proximal fragment during the fracture reduction, can avoid secondary injury of the muscles around the femoral bone caused by over-distraction, and effectively improve the safety of robot reduction operation.


Optimal control of aging in complex networks.
Many complex systems experience damage accumulation, which leads to aging, manifest as an increasing probability of system collapse with time. This naturally raises the question of how to maximize health and longevity in an aging system at minimal cost of maintenance and intervention. Here, we pose this question in the context of a simple interdependent network model of aging in complex systems and show that it exhibits cascading failures. We then use both optimal control theory and reinforcement learning alongside a combination of analysis and simulation to determine optimal maintenance protocols. These protocols may motivate the rational design of strategies for promoting longevity in aging complex systems with potential applications in therapeutic schedules and engineered system maintenance.


Bovine kidney alkaline phosphatase. Catalytic properties, subunit interactions in the catalytic process, and mechanism of Mg2+ stimulation.
Kidney alkaline phosphatase is an enzyme which requires two types of metals for maximal activity: zinc, which is essential, and magnesium, which is stimulatory. The main features of the Mg2+ stimulation have been analyzed. The stimulation is pH-dependent and is observed mainly between pH 7.5 and 10.5. Mg2+ binding to native alkaline phosphatase is characterized by a dissociation constant of 50 muM at pH 8.5,25 degrees. Binding of Zn2+ is an athermic process. Both the rate constants of association, ka, and of dissociation, kd, have low values. Typical values are 7 M(-1) at pH 8.0, 25 degrees, for ka and 4.10(-4) S(-1) at pH 8.0, 25 degrees, for kd. The on and off processes have high activation energies of 29 kcal mol (-1). Mg2+ can be replaced at its specific site by Mn2+, Co2+, Ni2+, and Zn2+. Zinc binding to the Mg2+ site inhibits the native alkaline phosphatase. Mn2+, Co2+, and Ni2+ also bind to the Mg2+ site with a stimulatory effect which is nearly identic-al with that of Mg2+, Mn2+ is the stimulatory cation which binds most tightly to the Mg2+ site; the dissociation constant of the Mn2+ kidney phosphatase complex is 2 muM at pH 8.5. The stoichiometry of Mn2+ binding has been found to be 1 eq of Mn2+ per mol of dimeric kidney phosphatase. The native enzyme displays absolute half-site reactivity for Mn2+ binding. Mg2+ binding site and the substrate binding sites are distinct sites. The Mg2+ stimulation corresponds to an allosteric effect. Mg2+ binding to its specific sites does not affect substrate recognition, it selectively affects Vmax values. Quenching of the phosphoenzyme formed under steady state conditions with [32P]AMP as a substrate as well as stopped flow analysis of the catalyzed hydrolysis of 2,4-dinitrophenyl phosphate or p-nitrophenyl phosphate have shown that the two active sites of the native and of the Mg2+-stimulated enzyme are not equivalent. Stopped flow analysis indicated that one of the two active sites was phosphorylated very rapidly whereas the other one was phosphorylated much more slowly at pH 4.2. Half of the sites were shown to be reactive at pH 8.0. Quenching experiments have shown that only one of the two sites is phosphorylated at any instant; this result was confirmed by the stopped flow observation of a burst of only 1 mol of nitrophenol per mol of dimeric phosphatase in the pre-steady state hydrolysis of p-nitrophenyl phosphate. The half-of-the-sites reactivity observed for the native and for the Mg2+-stimulated enzyme indicates that the same type of complex, the monophosphorylated complex, accumulates under steady state conditions with both types of enzymes. Mg2+ binding to the native enzyme at pH 8.0 increases considerably the dephosphorylation rate of this monophosphorylated intermediate. A possible mechanism of Mg2+ stimulation is discussed.


Effect of antiandrogen treatment on bone density and bone geometry in adolescents with polycystic ovary syndrome.
To determine the impact of antiandrogen treatment on bone density and geometry. Prospective cohort investigation. Academic research institute. 38 (age 14.96 ± 1.42 yr) subjects with PCOS. Treated with metformin (n = 17) or metformin and antiandrogen (n = 21). Bone density and geometry parameters at baseline and after a mean duration of 1.92 ± 0.88 years using peripheral quantitative computed tomography of the forearm. At baseline, z-scores for trabecular (0.53 ± 1.02) and cortical BMD (0.79 ± 1.55) as well as total (0.62 ± 1.07) and medullary cross sectional area (CSA) (0.79 ± 1.29) were elevated. Cortical CSA (-0.01 ± 1.10) and bone strength strain index (SSI) z-scores (-0.01 ± 1.10) were normal. Muscle CSA z-score (0.12 ± 1.70) was normal, but grip strength (-1.60 ± 1.15) was significantly reduced. There were no significant changes within and between the two treatment options in respect to bone density and bone geometry parameters. With antiandrogen treatment, free androgen index (FAI) was significantly lower and grip strength further decreased (P < .001). No significant changes in bone mineral density and geometry parameters took place in PCOS women irrespective of treatment followed over a time of almost two years. General muscle weakness expressed as low grip strength may influence further bone development in PCOS.


Clinical and radiological long-term follow-up after embolization of pulmonary arteriovenous malformations.
The purpose was to evaluate the clinical and radiological long-term results of embolization of pulmonary arteriovenous malformations (PAVMs) and to assess the quality of life after treatment. A clinical follow-up was undertaken after 67 months (mean) in 35 consecutive patients with 106 PAVMs. Outcome parameters at follow-up were PaO(2) and patients' satisfaction. During follow-up, the patients had a clinical examination, measurement of arterial blood gases, chest X-ray, and contrast echocardiography performed and were asked to fill in a questionnaire exploring experience of the treatment and subjective effect of treatment on physical and social functioning. A significant rise in oxygenation of the blood after embolization was measured. In 77% of the patients symptoms improved, and 71% felt better performance. In eight patients, one of the PAVMs was found insufficiently embolized or recanalized at follow-up angiography and therefore were re-embolized. Endovascular embolization for PAVMs is effective. Clinical parameters and quality of life improved significantly. Regular clinical controls after therapy are necessary to discover insufficiently embolized, recanalized or new PAVMs.


Prorenin anno 2008.
For many years, prorenin has been considered to be nothing more than the inactive precursor of renin. Yet, its elevated levels in diabetic subjects with microvascular complications and its extrarenal production at various sites in the body suggest otherwise. This review discusses the origin, regulation, and enzymatic activity of prorenin, its role during renin inhibition, and the angiotensin-dependent and angiotensin-independent consequences of its binding to the recently discovered (pro)renin receptor. The review ends with the concept that prorenin rather than renin determines tissue angiotensin generation.


Association between a dopamine-4 receptor polymorphism and blood pressure.
Dopamine receptor genes are candidates for hypertension susceptibility. Locally released dopamine increases renal sodium excretion, and defective renal dopamine receptor signaling has been shown to play a role in hypertension. Dopamine-4 receptors are expressed in juxtaglomerular and cortical collecting cells, where dopamine activation could alter sodium and water metabolism and affect blood pressure (BP). The dopamine-4 receptor (DRD4) gene has a 16 amino acid (48 base pairs [bp]) repeat polymorphism located in exon 3 where a G-protein binding area is encoded. The long allele (defined as at least one 7 to 10 repeat) has been associated with the personality trait Novelty Seeking and with substance abuse, but associations between dopamine-4 receptor polymorphisms and BP have not been reported. We genotyped 479 female and 385 male subjects of white ethnicity at the DRD4 repeat polymorphism site and classified each subject as having either the long or short genotype. We found associations between the DRD4 long allele and increased systolic BP (P = .031), diastolic BP (P = .034), and a history of regular alcohol use (P = .008). Furthermore, for systolic BP (P = .009) and pulse pressure (P = .002), we found evidence for an interaction between dopamine-4 receptor alleles and age, indicating that the effects of dopamine-4 receptor variants on BP increase with age. In this white population, the long variant of the DRD4 gene is associated with a 3-mm Hg higher systolic and 2-mm Hg higher diastolic BP.


A dual-channel fluorescent nanoprobe for accurate cancer diagnosis by sequential detection of adenosine triphosphate and sulfur dioxide.
Cancer is one of the major diseases that seriously endanger the health of all mankind. Accurate diagnosis of early cancer is the most promising way to reduce cancer harm and improve patient survival. However, many developed fluorescent probes for cancer imaging only have the function of identifying one marker, which cannot meet the needs of accurate diagnosis. Here, a fluorescent nanoprobe (CPH@ZIF-90) utilizing ZIF-90 to encapsulate SO2-sensitive dye (CPH) is synthesized for the sequential detection of ATP and SO2. The nanoprobe first interacts with ATP to release CPH, thus increasing the fluorescence at 685 nm and realizing the near-infrared (NIR) fluorescence detection of ATP. Then, SO2 acts on the released CPH through nucleophilic addition, affecting the π-conjugated structure of CPH and resulting in enhanced fluorescence at 580 nm. CPH@ZIF-90 exhibits satisfactory sensitivity and selectivity for sequential detection of ATP and SO2. Excitedly, CPH@ZIF-90 can sequentially image the endogenous ATP and SO2 in cells, showing sensitive fluorescence changes in dual channels (red and green). Due to the NIR emission properties of CPH@ZIF-90 and its ability to enrich in tumor, it is applied to monitor ATP and SO2 in mice and distinguish normal mice from tumor mice. The ability of CPH@ZIF-90 to sequentially detect two cancer-related biomarkers makes it provide meaningful assistance in accurate early diagnosis of cancer.


Outbreak of tularaemia in Golcuk, Turkey in 2005: report of 5 cases and an overview of the literature from Turkey.
Tularaemia was diagnosed by TaqMan RT-PCR and microagglutination tests in 5 patients, all from a new settlement constructed after the earthquake of 1999. During the follow-up, 129 more cases were found in this settlement (data from the local Health Care Authority). In this study, clinical features of 5 cases are presented briefly, and the Turkish literature on past outbreaks of tularaemia is reviewed.


RBR: library-less repeat detection for ESTs.
Repeat sequences in ESTs are a source of problems, in particular for clustering. ESTs are therefore commonly masked against a library of known repeats. High quality repeat libraries are available for the widely studied organisms, but for most other organisms the lack of such libraries is likely to compromise the quality of EST analysis. We present a fast, flexible and library-less method for masking repeats in EST sequences, based on match statistics within the EST collection. The method is not linked to a particular clustering algorithm. Extensive testing on datasets using different clustering methods and a genomic mapping as reference shows that this method gives results that are better than or as good as those obtained using RepeatMasker with a repeat library. The implementation of RBR is available under the terms of the GPL from http://www.ii.uib.no/~ketil/bioinformatics firstname.lastname@example.com Supplementary data are available at Bioinformatics online.


Telomere maintenance without telomerase.
Recombination-dependent maintenance of telomeres, first discovered in budding yeast, has revealed an alternative pathway for telomere maintenance that does not require the enzyme telomerase. Experiments conducted in two budding yeasts, S. cerevisiae and K. lactis, have shown recombination can replenish terminal G-rich telomeric tracts that would otherwise shorten in the absence of telomerase, as well as disperse and amplify sub-telomeric repeat elements. Investigation of the genetic requirements for this process have revealed that at least two different recombination pathways, defined by RAD50 and RAD51, can promote telomere maintenance. Although critically short telomeres are very recombinogenic, recombination among telomeres that have only partially shortened in the absence of telomerase can also contribute to telomerase-independent survival. These observations provide new insights into the mechanism(s) by which recombination can restore telomere function in yeast, and suggest future experiments for the investigation of potentially similar pathways in human cells.


Top 10 things to know about lupus activity measures.
Accurately measuring lupus disease activity has been a demanding and still unresolved task, considering the complex multisystem nature of the disease and its variability over time and between patients. Various available tools for measurement of lupus disease activity may detect clinical improvement and/or deterioration and can be global or organ-focused. Several measures have demonstrated validity, reliability, and sensitivity to change in observational studies, and some were found useful in randomized controlled trials. Evaluation of their content and metric properties and critical review of their strengths and weaknesses facilitates selection of the appropriate tool according to the outcome of interest, and forms the basis for their optimization. In this review, we highlight recent progress in lupus disease activity measures and point to future directions in this field, with a focus on novel composite measurements derived by combining outcome measures in ways that might compensate for their individual deficiencies.


Symptom remission in first episode patients.
Recently, new remission criteria for schizophrenia has been proposed, based on low symptom severity of core symptoms (the severity criteria), which is sustained over a minimum of 6 months (time criterion). The purpose of this study was to examine, in a secondary analysis, these criteria in a cohort of 240 first episode patients with a mean follow-up of 26.4 months from the Calgary Early Psychosis Program. Eighty-eight subjects (36.7%) met both the severity criteria and time criteria for remission (in-remission group); 47 subjects (19.6%) met only the severity criteria at their most recent assessment (severity only group); 49 (20.4%) subjects had met severity criteria at one or more assessments but did not meet severity or severity and time at the most recent assessment (fluctuating group); and 56 (23.3%) did not meet remission criteria (non-remission group). Those who achieved remission had lower levels of symptoms and higher functioning at baseline and at the final follow-up assessment, improved premorbid functioning, shorter duration of untreated psychosis and increased changes in symptoms over time.


Engineered nanoparticles of Efavirenz using methacrylate co-polymer (Eudragit-E100) and its biological effects in-vivo.
Nanotechnology in drug delivery is explored widely to improve therapeutic efficacy and minimize undesirable effects of several anti-HIV drugs. Efavirenz is a non-nucleoside reverse transcriptase inhibitor, prescribed as first-line drug of choice for treatment of AIDS. It is poorly soluble and exhibits variable bioavailability hence, a high oral dose is recommended for therapy. The present work focuses on improving the dissolution and bioavailability of Efavirenz through nano drug delivery approach. Polymeric nanoparticles were developed using Eudragit E100 and characterized for size, stability, morphology, cytotoxicity (MTT assay in T-lymphatic (C8166) cell lines) and in-vivo biodistribution in mice models. The optimized nanoparticles exhibited average particle size of 110nm, zeta potential of -33mV and entrapment efficiency 99%. The SEM images displayed the formation of nano-size particles. The cell viability was significantly improved in the nanoparticles (99%) compared to pure drug (15%) at the concentration of 8μg/mL. The in-vivo biodistribution profile of the nanoparticles showed considerably higher drug concentration in serum and major organs, especially in the brain compared to the free drug. The optimized Efavirenz loaded nanoparticles clearly demonstrated an increase in dissolution, drug distribution, and bioavailability, which implies better control over the therapeutic dosing.


Effect of atorvastatin on ApoE and ApoC-I synthesis and secretion by THP-1 macrophages.
Apolipoprotein (apo) E and C-I are plasma apolipoproteins that have been implicated in the etiology of atherosclerosis and obesity, respectively. Both proteins are synthesized and secreted by macrophages, though pharmacological regulation of their production is poorly understood. The authors compared the effect of 2 HMG-CoA reductase inhibitors, atorvastatin and cerivastatin, on the synthesis and secretion of apoE and apoC-I by THP-1 macrophages. Atorvastatin reduced medium apoE and cellular apoE mRNA of PMA-activated THP-1 cells in a dose-dependent manner (-24% and -22%, respectively, at 1-micromol/L, P < 0.01). ApoC-I in the medium was also reduced by atorvastatin in a dose-dependent manner, though to a lesser extent (-15% at 1-micromol/L, P < 0.05). Cerivastatin similarly reduced medium apoE (-20% at 1-micromol/L, P < 0.05) and cellular apoE mRNA (-31% at 1-micromol/L, P < 0.05), and significantly lowered cellular apoC-I mRNA (-15%, P < 0.05), but not apoC-I in the medium. In experiments with THP-1 macrophages loaded with cholesterol (ie, 24-hour incubation with acetyl-LDL), atorvastatin and cerivastatin (1-micromol/L) significantly (P < 0.05) reduced both medium apoE (-30% and -25%, respectively) and cellular apoE mRNA (-25% and -17%, respectively). A lower and less consistent effect was observed on medium apoC-I (-6% and -18%, respectively) and cellular apoC-I mRNA (-13% and -19%, respectively). These data demonstrate that statins have the capacity to reduce the synthesis and secretion of both apoE and apoC-I in THP-1 macrophages loaded or unloaded with cholesterol.


Influence of spectral detector CT based monoenergetic images on the computer-aided detection of pulmonary artery embolism.
To evaluate the influence of monoenergetic reconstructions using a spectral detector CT (SDCT) on the computer aided detection (CAD) of pulmonary artery embolism (PAE) on CT pulmonary angiography (CTPA) and CT in venous contrast phase (CTV). A retrospective data base search identified 15 patients with CTPA and 18 patients with CTV and diagnosis of PAE. For these patients, monoenergetic (monoE) images at different energy levels or with a fixed attenuation in the pulmonary artery were generated and independently analyzed using a commercially available computer aided detection (CAD) tool. Attenuation in the pulmonary artery and in the embolus was measured. For CTPA and CTV, in monoenergetic images the difference in attenuation between vessel and embolus was significantly higher than in conventional images. In CTPA the detection rate was highest in the >500 HU monoE images with 67,9% detected emboli and 93,3% of patients correctly identified as having PAE. At the same time the false positive rate could be significantly reduced by using monoE images compared to conventional images. Detection rates for CTV were lower than in CTPA but were raised significantly by monoE reconstructions. The combination of SDCT and CAD improves the diagnostic accuracy of CAD and enables CAD interpretation of CTV.


CAVITARY CHOROIDAL NEVUS: A CASE REPORT.
To describe a case of choroidal nevus with intralesional cavitations detected with enhanced depth imaging optical coherence tomography and to show its changes during an 8-year follow-up. A case report. A 55-year-old male patient was found to have a pigmented lesion at the posterior pole of his right eye, just temporal to the fovea. A complete multiimaging examination was obtained and showed a lesion of about 4 mm of diameter with a small amount of subretinal fluid and chronic changes in the retina overlying the lesion. Based on clinical examination, a diagnosis of choroidal nevus was made, but interestingly the enhanced depth imaging optical coherence tomography revealed the presence of intralesional cavitations. Close follow-up with no intervention was planned, and over 8 years of observation, the lesion remained stable in size, with a gradual increase of the central necrosis. Benign pigmented choroidal lesions can show internal cavitations likely secondary to internal necrosis. This feature does not represent a sign of malignancy of the lesion. Enhanced depth imaging optical coherence tomography is a feasible imaging tool for the visualization of the internal cavitations and to follow their evolution over time.


Seed grants as a means of stimulating cancer research funding.
Seed grant programs have been suggested as an innovative way to launch new initiatives. We evaluated one such program designed to stimulate cancer research in a state with little to moderate cancer research activity. Success was defined as the ability of seed grant recipients to develop proposals, obtain external funding and publish the results of cancer-related research. Data were collected through the Internet from a variety of funding and publication databases, as well as through updated curriculum vitae and a mail survey of the seed grant recipients. Fifteen (31%) experienced investigators and 33 (69%) new investigators credited their seed grants with helping them leverage 60 active research grants and 10 pending proposals with a variety of funders. Overall, seed grant recipients leveraged $10.10 for every dollar of seed grant funding they received. Anecdotal evidence showed that seed grants allowed grantees to establish themselves as legitimate cancer research investigators, develop and fund their laboratories, and focus or refocus their work. These results are from a single case study. Seed grants for pilot projects inexpensively and efficiently built cancer research capacity in a state with historically low levels of national cancer research funding. As our findings are based on a single case study, we cannot state that this strategy would succeed for other states in similar circumstances.


Comprehensive monitoring of synthetic musk compounds from freshwater to coastal environments in Korea: with consideration of ecological concerns and bioaccumulation.
This study investigated the concentration levels of synthetic musk compounds (SMCs), including HHCB (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-(g)-2-benzopyran), AHTN (7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene), MK (Musk ketone), and MX (Musk xylene), in freshwater, freshwater and coastal sediments, and coastal bivalves from freshwater to coastal environments. The levels in freshwater close to sewage treatment plants (STPs) showed higher contamination and suggested a medium to high ecological risk, especially posed by MK making more than 65% contribution to the combined risk by the total SMCs. STP effluent discharge points showed higher SMC concentrations in freshwater and coastal sediments. Predominant HHCB contributions regardless of sample types such as abiota and biota were consistent with the greater usage of HHCB than AHTN and MK in Korea. However, the higher contributions of AHTN than those predicted from AHTN consumption in Korea indicate the need for further research on the characteristic properties of individual SMCs, including partitioning, biomagnification, degradation, and metabolism for a realistic risk characterization. With respect to the highest HHCB levels in coastal bivalves reported, we determined the biota-sediment accumulation factor (BSAF) to understand the bioaccumulation of SMCs between coastal sediment and bivalves. The calculated BSAF values suggested that SMCs in bivalves were not biomagnified via the food chain but mostly partitioned from sediment. To our knowledge, this is the first study to measure BSAF values of SMCs, especially HHCB, AHTN, and MK, in coastal bivalve samples.


The putative metabolic role of d-chiro inositol phosphoglycan in human pregnancy and preeclampsia.
Immunological alterations, systemic inflammation, endothelial dysfunction, and insulin resistance are prominent features of preeclampsia, although the reciprocal relationship between them is poorly understood. The metabolic syndrome that occurs during preeclampsia can be exacerbated by the systemic inflammation and linked to placental metabolism/development and endothelial dysfunction. Under healthy conditions, insulin and insulin-like growth factor-integrated pathways not only promote cell metabolism and proliferation, but also regulate endothelial synthesis and release of vasodilators (e.g., nitric oxide, NO) and opposing vasoconstrictors (e.g., endothelin-1) to maintain vascular homeostasis. d-chiro inositol phosphoglycans (DCI), second messengers of insulin, are increased during preeclampsia and contribute directly to insulin resistance. The dynamic balanced control of vascular function may be altered by excessive DCI that impairs the PI3-kinase-dependent pathway and may result in reduced bioavailability of NO, contributing to elevated peripheral vascular resistance and hypertension.


ClC-c regulates the proliferation of intestinal stem cells via the EGFR signalling pathway in Drosophila.
Adult stem cells uphold a delicate balance between quiescent and active states, which is crucial for tissue homeostasis. Whereas many signalling pathways that regulate epithelial stem cells have been reported, many regulators remain unidentified. Flies were used to generate tissue-specific gene knockdown and gene knockout. qRT-PCR was used to assess the relative mRNA levels. Immunofluorescence was used to determine protein localization and expression patterns. Clonal analyses were used to observe the phenotype. RNA-seq was used to screen downstream mechanisms. Here, we report a member of the chloride channel family, ClC-c, which is specifically expressed in Drosophila intestinal stem/progenitor cells and regulates intestinal stem cell (ISC) proliferation under physiological conditions and upon tissue damage. Mechanistically, we found that the ISC loss induced by the depletion of ClC-c in intestinal stem/progenitor cells is due to inhibition of the EGFR signalling pathway. Our findings reveal an ISC-specific function of ClC-c in regulating stem cell maintenance and proliferation, thereby providing new insights into the functional links among the chloride channel family, ISC proliferation and tissue homeostasis.


Waste preserved wood derived biochar catalyst for promoted peroxymonosulfate activation towards bisphenol A degradation with low metal ion release: The insight into the mechanisms.
The rational disposal of waste preserved wood is of great significance since its embedded metals (Cu, As, and Cr) pose potential threat to environment and human health. In this study, a biochar catalyst derived from waste preserved wood (PWB) was prepared for the degradation of bisphenol A (BPA) via peroxymonosulfate (PMS) activation. The PWB exhibited prominent catalytic degradation capability towards BPA compared with common wood derived biochar (CWB). Further tests and analysis elucidated that both radical species (OH) and non-radical species (1O2) were generated by the PWB/PMS system, whereas only 1O2 was detected in CWB/PMS system. Specifically, the metal compounds, especially metallic Cu in the PWB activated PMS via radical pathway, and the CO groups in the biochar generated the non-radical pathway, the coexistence of which resulted in higher BPA degradation rate in PWB/PMS system. It was also demonstrated that the heavy metal ion leaching (As and Cr) in PWB/PMS system was negligible. Furthermore, the biochar could effectively inhibit the leakage of oxidized Cu ions. This study provides a novel approach to prepare high-efficient carbocatalysts for organic pollutant degradation in water, which also enables the waste preserved wood with an environmental nondestructive mode of dispatch.


Cerebral infarction in the caudate nucleus associated with acute epidural hematoma and diffuse brain injury in a child after severe head injury.
A 6-year-old boy was admitted to our hospital 20 min after receiving a direct impact to his head in an automobile accident. He was semi-comatose on admission and computed tomography showed acute epidural hematoma in the right supratentorial region. Three hours later, his consciousness deteriorated due to the enlargement of the hematoma. Surgical removal of hematoma relieved his consciousness disturbance. Post-operative magnetic resonance imaging revealed spotty high-intensity lesions in the corpus callosum on T2-weighted images, and a solitary high-intensity lesion in the left caudate nucleus extending to the medial globus pallidum on T2-weighted and diffusion-weighted images. Magnetic resonance angiography showed no abnormality in the main arteries. These results suggested cerebral infarction in the vascular territory supplied by the recurrent artery of Heubner in association with diffuse brain injury. Post-operative course was uneventful and he was discharged without neurological deficit. Post-traumatic cerebral infarction in the caudate nucleus is extremely rare, and its association with diffuse brain injury and epidural hematoma is apparently unique.


GPI-anchored aminopeptidase is involved in the acrosome reaction in sperm of the mussel mytilusedulis.
The sperm of the mussel Mytilus had hydrolytic activities against substrates for aminopeptidase. Acrosome reaction (AR) was suppressed in the presence of aminopeptidase substrate, Phe-4-methylcoumaryl-7-amide (MCA), and an aminopeptidase inhibitor, bestatin. Treatment of sperm with phosphatidylinositol-specific phospholipase C (PI-PLC) released aminopeptidase activity from sperm and suppressed AR. These results suggest that the enzyme is located on the sperm surface via glycosylphosphatidylinositol (GPI)-anchor and is involved in the AR. Immunoblot analysis showed that tyrosine residues of 40, 59, 68, and 72 kDa proteins were phosphorylated during induction of the AR. The 40 kDa protein was also recognized by anti-c-Src antibody by immunoblotting. The tyrosine phosphorylation of these proteins was inhibited when sperm were inseminated in the presence of Phe-MCA, and by PI-PLC treatment. Treatment of sperm with tyrosine kinase activator, 9,10-dimethyl-1,2-benzanthracene, induced AR, and its inhibitor, genistein, suppressed AR. These results suggest that tyrosine phosphorylation of 40, 59, 68, and 72 kDa proteins, induced by the interaction of GPI-anchored aminopeptidase with oocyte surface, triggers AR in Mytilus sperm.


Differential interaction of reovirus type 3 with sialylated receptor components on animal cells.
In this report we study the interaction of reovirus type 3 Dearing (RV3) with vertebrate erythrocytes whose membrane glycoconjugates differ in the degree and position of O-acetylation of their sialic acid (NeuAc) residues. Binding to erythrocytes required the presence of NeuAc on cellular glycoconjugates, since pretreatment with sialidase (neuraminidase) abolished hemagglutination by RV3. Furthermore, we found that RV3 binds efficiently to and hemagglutinates all erythrocyte preparations possessing exclusively NeuAc, or a mixture of NeuAc and 4-O-acetyl-NeuAc (4-O-Ac-NeuAc), but poorly to erythrocytes bearing a mixture of 9-O-Ac-NeuAc and NeuAc, suggesting that RV3 binds preferentially to NeuAc-containing glycoconjugates. To gain further evidence for this hypothesis we treated chicken erythrocytes with influenza C virus neuraminate, 9-O-acetylesterase, to convert their 9-O-Ac-NeuAc residues to NeuAc. When hemagglutination assays were carried out on these cells, we observed a 16-fold increase in the hemagglutination titer for RV3 compared to untreated cells. When we treated bovine submaxillary mucin (BSM) with influenza C virus, we observed a dramatic increase in its potency as an inhibitor of RV3 hemagglutination. Concomitant with this, the 9-O-Ac-NeuAc residues on BSM were converted to NeuAc. Taken together and in conjunction with a previous report (A. F. Pacitti and J. R. Gentsch, 1987, J. Virol. 61 1407-1415), these results suggest that the virion attachment protein exhibits a strong preference for NeuAc over 9-O-Ac-NeuAc as a receptor component on erythrocytes.


A New Tool for the Analysis of the Effect of Intracerebrally Injected Anti-Amyloid-β Compounds.
A wide range of techniques has been developed over the past decades to characterize amyloid-β (Aβ) pathology in mice. Until now, no method has been established to quantify spatial changes in Aβ plaque deposition due to targeted delivery of substances using ALZET® pumps. Development of a methodology to quantify the local distribution of Aβ plaques after intracerebral infusion of compounds. We have developed a toolbox to quantify Aβ plaques in relation to intracerebral injection channels using Zeiss AxioVision® and Microsoft Excel® software. For the proof of concept, intracerebral stereotactic surgery was performed in 50-day-old APP-transgenic mice injected with PBS. At the age of 100 days, brains were collected for immunhistological analysis. The toolbox can be used to analyze and evaluate Aβ plaques (number, size, and coverage) in specific brain areas based on their location relative to the point of the injection or the injection channel. The tool provides classification of Aβ plaques in pre-defined distance groups using two different approaches. This new analytic toolbox facilitates the analysis of long-term continuous intracerebral experimental compound infusions using ALZET® pumps. This method generates reliable data for Aβ deposition characterization in relation to the distribution of experimental compounds.


Critical Periods in Vision Revisited.
For four decades, investigations of the biological basis of critical periods in the developing mammalian visual cortex were dominated by study of the consequences of altered early visual experience in cats and nonhuman primates. The neural deficits thus revealed also provided insight into the origin and neural basis of human amblyopia that in turn motivated additional studies of humans with abnormal early visual input. Recent human studies point to deficits arising from alterations in all visual cortical areas and even in nonvisual cortical regions. As the new human data accumulated in parallel with a near-complete shift toward the use of rodent animal models for the study of neural mechanisms, it is now essential to review the human data and the earlier animal data obtained from cats and monkeys to infer general conclusions and to optimize future choice of the most appropriate animal model.


Are patient symptoms predictive of the diagnostic and/or therapeutic value of hydrodistention?
Hydrodistention (HD) has been utilized as a diagnostic and therapeutic tool in patients with refractory and diverse pelvic floor symptoms, including bladder pain with or without irritative bladder symptoms such as urinary urgency and urinary frequency. We sought to determine whether we could better define in whom HD was a more valuable intervention by stratifying patients according to presenting symptoms. A retrospective review was performed on 185 patients who underwent HD at our institution by a single surgeon between 1/2002-8/2004. Subjects were placed into groups according to their symptoms. Group 1 (G1) patients reported pain with bladder filling that was relieved with emptying, group 2 (G2) reported constant pelvic pain unrelated to bladder filling or emptying, and group 3 (G3) reported urgency and frequency alone with no pain component. Anesthetic capacity, presence and severity of glomerulations post-distention, and follow-up at 1, 3, and 6 months were recorded for each patient. G1 included 40 patients with mean age of 42 (R = 16-77), G2 included 101 patients with mean age of 46 (R = 20-76), and G3 22 patients with mean age of 40 (R = 20-84). The mean anesthetic capacity was 715 ml, 725 ml, and 542 ml for G1, G2, and G3 respectively. ANOVA revealed a statistically significant reduction in the capacity of G3 when compared with the others (P = 0.0072). Glomerulations were present in 74% of G1, 72% of G2, and 86% of G3 patients. 61%, 33%, & 0% of G1 patients reported improvement at 1, 3, and 6 months respectively, 54%, 25%, & 7% of G2 patients reported improvement, and 50%, 19%, & 7% of G3 patients reported improvement. There were no statistically significant differences in the responses amongst the three groups. Although HD is frequently employed for patients with refractory pelvic pain and/or lower urinary tract complaints, results failed to identify any statistically significant differences in post-distention objective findings (anesthetic capacity, glomerulations) or therapeutic benefits when patients are categorized according to presenting symptoms.


Consumption of star fruit juice on pro-inflammatory markers and walking distance in the community dwelling elderly.
This study aimed to evaluate the effect of star fruit juice supplementation on tumor necrosis factor-alpha (TNF-α), interleukin-23 (IL-23) and interleukin-2 (IL-2), nitric oxide (NO), and 6 min walking distance (6MWD) in a group of elderly individuals. Twenty-nine individuals (20 males, 9 females) with a mean age of 72.4±8.3 years completed this study. A two-week control period was followed by four weeks of 100g fresh star fruit juice consumption twice per day after meals. Plasma TNF-α, IL-23, IL-2, NO and the 6MWD were evaluated twice during the control period (weeks 0 and 2) and once after the star fruit juice consumption (week 6). The results showed that all parameters in the blood did not change significantly during the control period. After 4 weeks of star fruit juice consumption, a significant reduction in NO, TNF-α and IL-23 was found; however, there was no change in IL-2. Moreover, the 6MWD increased significantly at week 6, when compared to that at week 0 and 2. Furthermore, the results also showed a significantly positive and negative correlation of NO and TNF-α to the 6MWD, but no correlation of IL-23 and IL-2. This preliminary study concluded that consumption of star fruit juice at 100g twice daily for one month can significantly depress the pro-inflammation cytokines: TNF-α, IL-23, and NO, while increasing walking distance. Low TNF-α and high NO also present a significant correlation to walking capacity in elderly individuals.


Activation of the Nlrp3 inflammasome in infiltrating macrophages by endocannabinoids mediates beta cell loss in type 2 diabetes.
Type 2 diabetes mellitus (T2DM) progresses from compensated insulin resistance to beta cell failure resulting in uncompensated hyperglycemia, a process replicated in the Zucker diabetic fatty (ZDF) rat. The Nlrp3 inflammasome has been implicated in obesity-induced insulin resistance and beta cell failure. Endocannabinoids contribute to insulin resistance through activation of peripheral CB1 receptors (CB₁Rs) and also promote beta cell failure. Here we show that beta cell failure in adult ZDF rats is not associated with CB₁R signaling in beta cells, but rather in M1 macrophages infiltrating into pancreatic islets, and that this leads to activation of the Nlrp3-ASC inflammasome in the macrophages. These effects are replicated in vitro by incubating wild-type human or rodent macrophages, but not macrophages from CB₁R-deficient (Cnr1(-/-)) or Nlrp3(-/-) mice, with the endocannabinoid anandamide. Peripheral CB₁R blockade, in vivo depletion of macrophages or macrophage-specific knockdown of CB₁R reverses or prevents these changes and restores normoglycemia and glucose-induced insulin secretion. These findings implicate endocannabinoids and inflammasome activation in beta cell failure and identify macrophage-expressed CB₁R as a therapeutic target in T2DM.


Early confocal microscopy findings after cross-linking treatment.
To determine the effects of in vivo cross-linking treatment of the cornea. Eighteen eyes of eighteen keratoconus patients underwent cross-linking treatment using a 0.1% riboflavin solution and ultraviolet A radiation at 370 nm at 3 mW/cm² for 30 minutes. In vivo confocal microscopy was performed before, and at 1 week and 1 month after treatment. At 1 week after treatment, keratocyte activation and collagen fiber organization showed as hyper-reflective structures and were observed from the first sub-epithelial image to a corneal stromal depth of 275.1 ± 85.9 μm. At 1 month after treatment, activated keratocytes and fiber organization were also observed from the first sub-epithelial image to a corneal stromal depth of 324.9 ± 66.0 μm. The deepest hyper-reflective structures at 1 month showed as thick, linear-shaped hyper-reflective structures. In vivo confocal microscopy in humans showed corneal stromal changes at 1 week and 1 month after cross-linking treatment, in some cases at depths in excess of 300 μm.


Outcome of intracranial electroencephalography monitoring and surgery in magnetic resonance imaging-negative temporal lobe epilepsy.
We evaluated the outcomes of intracranial electroencephalography (iEEG) recording and subsequent resective surgery in patients with magnetic resonance imaging (MRI)-negative temporal lobe epilepsy (TLE). Thirty-two patients were identified from the Mayo Clinic Epilepsy Surgery Database (Arizona, Florida, and Minnesota). Eight (25.0%) had chronic iEEG monitoring that recorded neocortical temporal seizure onsets; 12 (37.5%) had mesial temporal seizure onsets; 5 (15.6%) had independent neocortical and mesial temporal seizure onsets; and 7 (21.9%) had simultaneous neocortical and mesial seizure onsets. Neocortical temporal lobe seizure semiology was the only factor significantly associated with neocortical temporal seizure onsets on iEEG. Only 33.3% of patients who underwent lateral temporal neocorticectomy had an Engel class 1 outcome, whereas 76.5% of patients with iEEG-guided anterior temporal lobectomy that included the amygdala and the hippocampus had an Engel class 1 outcome. Limitations in cohort size precluded statistical analysis of neuropsychological test data.


The roles of galectins in parasitic infections.
Galectins is a family of multifunctional lectins. Fifteen galectins have been identified from a variety of cells and tissues of vertebrates and invertebrates. Galectins have been shown to play pivotal roles in host-pathogen interaction such as adhesion of pathogens to host cells and activation of host innate and adaptive immunity. In recent years, the roles of galectins during parasite infections have gained increasing attention. Galectins produced by different hosts can act as pattern recognition receptors detecting conserved pathogen-associated molecular patterns of parasites, while galectins produced by parasites can modulate host responses. This review summarizes some recent studies on the roles of galectins produced by parasitic protozoa, nematodes, and trematodes and their hosts. Understanding the roles of galectins in host-parasite interactions may provide targets for immune intervention and therapies of parasitic infections.


QCM-based assay designs for human serum albumin.
Solid-phase synthesis is an elegant way to create molecularly imprinted polymer nanoparticles (nano-MIPs) comprising a single binding site, i.e. mimics of antibodies. When using human serum albumin (HSA) as the template, one achieves nano-MIPs with 53 ± 19 nm diameter, while non-imprinted polymer nanoparticles (nano-NIPs) reach 191 ± 96 nm. Fluorescence assays lead to Stern-Volmer plots revealing selective binding to HSA with selectivity factors of 1.2 compared to bovine serum albumin (BSA), 1.9 for lysozyme, and 4.1 for pepsin. Direct quartz crystal microbalance (QCM) assays confirm these results: nano-MIPs bind to HSA immobilized on QCM surfaces. This opens the way for competitive QCM-based assays for HSA: adding HSA to nanoparticle solutions indeed reduces binding to the QCM surfaces in a concentration-dependent manner. They achieve a limit of detection (LoD) of 80 nM and a limit of quantification (LoQ) of 244 nM. Furthermore, the assay shows recovery rates around 100% for HSA even in the presence of competing analytes.


Composite Proton Exchange Membranes Based on Chitosan and Phosphotungstic Acid Immobilized One-Dimensional Attapulgite for Direct Methanol Fuel Cells.
In order to obtain biopolymer chitosan-based proton exchange membranes with excellent mechanical properties as well as high ionic conductivity at the same time, natural attapulgite (AT) with one-dimensional (1D) structure was loaded with a strong heteropolyacid and also a super proton conductor, phosphotungstic acid (PWA), using a facial method. The obtained PWA anchored attapulgite (WQAT) was then doped into the chitosan matrix to prepare a series of Chitosan (CS)/WQAT composite membranes. The PWA coating could improve the dispersion and interfacial bonding between the nano-additive and polymer matrix, thus increasing the mechanical strength. Moreover, the ultra-strong proton conduction ability of PWA together with the interaction between positively charged CS chains and negatively charged PWA can construct effective proton transport channels with the help of 1D AT. The proton conductivity of the composite membrane (4 wt.% WQAT loading) reached 35.3 mS cm-1 at 80 °C, which was 31.8% higher than that of the pure CS membrane. Moreover, due to the decreased methanol permeability and increased conductivity, the composite membrane with 4% WQAT content exhibited a peak power density of 70.26 mW cm-2 fed at 2 M methanol, whereas the pure CS membrane displayed only 40.08 mW cm-2.


Benign paroxysmal positional vertigo: Effective diagnosis and treatment.
Benign paroxysmal positional vertigo (BPPV), caused by wayward crystals ("rocks") in the semicircular canals of the inner ear, is the most common cause of brief symptoms of vertigo secondary to head and body movements. Diagnosing and treating it are simple to do in the medical office. This article reviews the differential diagnosis for patients presenting with dizziness and vertigo, the pathophysiology of BPPV, how to diagnose it using maneuvers to elicit symptoms and nystagmus, how to interpret the nystagmus pattern to determine where the rocks are, and how to treat it using different maneuvers to reposition ("roll") the rocks back where they belong.


Epinephrine enhances analgesia produced by epidural bupivacaine during labor.
Reports on the analgesic and hemodynamic effects of epinephrine added to bupivacaine for epidural use in obstetrics are conflicting. In this study, healthy parturients received in a random manner either 10 ml of 0.25% bupivacaine (n = 50) or 10 ml of 0.25% bupivacaine with 1:300,000 epinephrine (n = 50) epidurally. Epinephrine enhanced the analgesia produced by bupivacaine: onset was hastened (5.8 +/- 0.6 vs 8.7 +/- 0.8 min, mean +/- SEM, P less than 0.05), duration prolonged (123 +/- 7.0 vs 92 +/- 5.0 min, P less than 0.05), and the number of women requiring additional local anesthetic for analgesia decreased (9 vs 18, P less than 0.05) compared to the group receiving plain bupivacaine. The incidence of hypotension did not differ between groups. Maternal heart rate increased only after injection of the epinephrine-containing solution. The authors conclude that epinephrine 1:300,000 modestly but statistically significantly improves the analgesic efficacy of epidurally administered 0.25% bupivacaine during labor.


Estimation of average muscle fiber conduction velocity from two-dimensional surface EMG recordings.
We propose a novel method for the estimation of muscle fiber conduction velocity (CV) from surface EMG recordings. The approach is based on the analysis of signals detected along a number of linear electrode arrays parallel to the fiber direction, thus collected by a bi-dimensional (2-D) array (matrix) of electrodes. The information provided by the 2-D array is used to derive a maximum likelihood estimator which can be applied to any number of signals and which may account for missing channels in the matrix. An iterative technique in the frequency domain for the estimation of the propagation delay is proposed to reduce the computational time and avoid the limit of resolution due to signal sampling. The method proposed is applied to signals collected from the biceps brachii muscle of eight healthy subjects during isometric, constant force contractions at 50% of the maximal voluntary contraction torque. It is shown that CV estimation standard deviation and sensitivity to electrode displacements significantly decrease by the application of the method proposed with respect to classic CV estimation techniques. The method promises to be a useful tool when average CV is estimated for muscle assessment and diagnostic purposes.


Do integrated record systems lead to integrated services? An observational study of a multi-professional system in a diabetes service.
There are few opportunities to study the use of integrated electronic health record (EHR) systems, where single patient records are used by a number of health care staff. The purpose of the study was to understand how an integrated electronic health record system was used by health care staff in the treatment and management of diabetes patients. The investigation was focused on the interface between the primary and secondary care services which patients access for their diabetes care. Observations of the use of an integrated electronic health record during patients' consultations with health care staff were conducted over a three month period. Twelve patients were followed through their consultations with a range of health care staff at a secondary care Diabetes Centre and in primary care settings. A thematic analysis of the observation data was undertaken. The integrated electronic health record system had been implemented across the primary and secondary care interface and was used by many, but not all, clinicians involved in the care of patients with diabetes. In some areas of care it enabled health care staff to access more accurate and detailed information to inform their clinical decision-making. Issues including negotiating rules for accessing patient records and duplication of recording in paper record systems had not been resolved consistently across services. The findings offer suggestive evidence that a shared electronic health record can support more integrated care. Unresolved issues in implementing the system across all services and settings highlight the governance problems that can arise when systems are developed locally but are then extended across organisational and professional boundaries.


Technology for microarray analysis of gene expression.
The past year has demonstrated the versatility of microarrays for the analysis of whole model-organism genomes and has seen the development of chips to measure the expression of 40,000 human genes. Microarray technology has also become considerably more robust and sensitive. Technology enhancements include the use of noncontact printing methods, improved 2-color sample preparation, and statistically based software for data analysis.


Ectopic secretion of chorionic gonadotropin by a lung carcinoma. Pituitary gonadotropin and subunit secretion and prolonged chemotherapeutic remission.
The ability of tumor markers to improve cancer therapy is not established. We studied a man with a human chorionic gonadotropin (HCG)-secreting large cell carcinoma of the lung and gynecomastia. Preoperatively, levels of HCG (109 ng/ml), its alpha and beta subunits (3.2 and 21 ng/ml, respectively) and plasma estradiol were elevated. Despite apparently complete tumor resection and total resolution of gynecomastia, HCG titers remained elevated (3.3 ng/ml), heralding tumor recurrence three weeks later. Because the pathophysiologic consequences of the ectopic secretion of HCG on pituitary function are not established, we administered 100 microgram of gonadotropin-releasing hormone (LHRH) and observed a markedly delayed increase in pituitary gonadotropins. Early chemotherapy, guided by persistence of HCG, reduced HCG to undetectable levels, restored to normal the response to LHRH and resulted in a distinctly unusual 30-month complete remission. Use of HCG as a tumor marker levels is more sensitive than the symptom of gynecomastia and may permit detection of small, potentially curable tumor foci.


Composition and factors influencing community structure of lactic acid bacterial in dairy products from Nyingchi Prefecture of Tibet.
This study investigated the community composition of lactic acid bacteria (LAB) from yaks' milk (YM) Tibetan yellow cattle milk (TM) and their fermented products from different counties in the Nyingchi Prefecture, Tibet using Pacific Biosciences (PacBio) single-molecule real-time (SMRT) sequencing. Sequencing revealed 26 genera and 94 species from 71 dairy samples; amongst these Lactobacillus delbrueckii (36.17%), Streptococcus thermophilus (19.46%) and Lactococcus lactis (18.33%) were the predominant species. This study also identified the main factors influencing LAB community composition by comparing amongst samples from different locations, from different milk types, and from different altitudes. The LAB communities in YM and TM were more diverse than in fermented yaks' milk (FYM) and fermented Tibetan yellow cattle milk (FTM) samples. Similarly, whether milk was fermented or not accounted for differences in LAB species composition while altitude of the dairy products had very little effect. Milk source and production process were the most likely causes of drastic shifts in microbial community composition. In addition, fermented dairy products were enriched in genes responsible for secondary metabolic pathways that were potentially beneficial for health. Comprehensive descriptions of the microbiota in different dairy products from the Nyingchi Prefecture, Tibet might help elucidate evolutionary and functional relationships amongst bacterial communities in these products.


Concern about COVID-19 among the Spanish population: Validation of a scale and associated symptoms.
The health crisis caused by the COVID-19 pandemic has led to a considerable increase in the psychopathology of COVID-19 patients and among the general population. This study aims to conduct the psychometric analysis of the scale of concern about COVID-19 in the Spanish population and to estimate the level of concern and dysfunctional anxiety present one year after the lockdown measures in Spain aimed at resisting the spread of the viral disease among the population. The factorial structure of the instrument, its reliability for the general population and for COVID patients, and its construct validity have been analyzed, and measurements of dysfunctional concern have been obtained from a sample of 502 adults. The scale of concern about COVID-19 showed optimal results of reliability and validity for the Spanish population, confirming that it is an ideal instrument for estimating the concern regarding coronavirus contagion. This study used a cross-sectional design and thus, could not compare the changes in the incidence of anxiety symptoms before and after the COVID-19 outbreak. Furthermore, the use of mental health services prior to the COVID-19 restrictions was not assessed in this study, and therefore, no comparisons between the two time points could be made. After a year of the confinement measures that was instilled to avoid further spread of the disease, the Spanish population presented levels of concern and anxiety that may require clinical attention, with a significant percentage of participants meeting the requirements to be diagnosed with generalized anxiety disorders.


Understanding Different Aspects of Caregiving for Individuals with Autism Spectrum Disorders (ASDs) a Narrative Review of the Literature.
There has been a considerable endeavor to understand associated challenges of caregiving for a child with Autism Spectrum Disorders (ASDs) and to develop the necessary skills and approaches to assist parents of children with ASD. Different studies have been stressed the importance and need for parental involvement in the intervention process to increase positive impacts. The process of caregiving and the associated challenges should be understood from different aspects to be able to facilitate parent involvement in intervention implementation. In a narrative literature review, ten selected reviews were considered and each review considered a special aspect of caregiving for an individual with ASD. Five main different factors in the available literature and reviews were considered as different themes that needed to be reconsidered in the studies on the impacts of caregiving for an individual with ASD. It is concluded that to facilitate parental involvement in the intervention process, and to support caregivers of this group of individuals this review highlights the need for improved research in some proposed areas in this field and to bridge the gap between research and practice in this field.


Protein Quantitation of the Developing Cochlea Using Mass Spectrometry.
Mass spectrometry-based proteomics allows for the measurement of hundreds to thousands of proteins in a biological system. Additionally, mass spectrometry can also be used to quantify proteins and peptides. However, observing quantitative differences between biological systems using mass spectrometry-based proteomics can be challenging because it is critical to have a method that is fast, reproducible, and accurate. Therefore, to study differential protein expression in biological samples labeling or label-free quantitative methods can be used. Labeling methods have been widely used in quantitative proteomics, however label-free methods have become equally as popular and more preferred because they produce faster, cleaner, and simpler results. Here, we describe the methods by which proteins are isolated and identified from cochlear sensory epithelia tissues at different ages and quantitatively differentiated using label-free mass spectrometry.


A duration matching method for the measurement of jitter in single fibre EMG.
A new microprocessor method for on-line measurement of jitter in SFEMG is described. The method is based on a duration matching procedure: automatic detection of the repetitive occurrence of two single fibre potentials with stable durations and time-locked to one another. During the investigation of a motor unit a potential pair is accepted or rejected for the determination of jitter on the basis of the potential durations and the interpotential interval; the time criteria are set by the first potential pair measured. The measuring device consists of a microprocessor and an analog interface; it is small and can be connected to any EMG equipment. Compared with the methods previously described the duration matching method (a simple pattern recognition procedure) has the following advantages: the measurement during activation of several motor units is faster and more reliable; the 'technical jitter' is smaller, which allows a more accurate determination of the normal range. Consequently, the method yields values of physiological jitter which are significantly smaller than those previously described.


A dose-ranging study of the effects of mequitazine on actual driving, memory and psychomotor performance as compared to dexchlorpheniramine, cetirizine and placebo.
Mequitazine is a so-called 'non-sedative' second-generation antihistamine even though it has never been firmly established that this drug's sedative potential actually differs from that of the 'sedative' first-generation antihistamines. The present study compares the sedative effects of three doses of mequitazine on actual driving, psychomotor performance and memory with those of a first- and a second-generation antihistamine. Eighteen healthy volunteers received on separate days a single dose of 5, 10 and 15 mg mequitazine, 10 mg cetirizine, 6 mg dexchlorpheniramine and placebo. Drug effects were assessed using two actual driving tests (highway-driving test and car-following test), cognitive and psychometric tests (tracking, divided attention, memory, reasoning and critical flicker fusion), pupil size and questionnaires. Highway-driving data revealed an overall effect of Treatment on the standard deviation of lateral position (SDLP). Dexchlorpheniramine impaired driving performance as indicated by a significant rise in SDLP. Mequitazine significantly increased SDLP in a dose-related manner, but the separate dose effects failed to reach statistical significance. Divided attention performance was also affected by Treatment. Reaction time (RT) during mequitazine treatments increased in a dose-related manner and significantly differed from placebo at the highest dose. Subjects reported to be less alert after treatment with dexchlorpheniramine. Cetirizine did not affect performance in any of the tasks. It was concluded that mequitazine is mildly sedating. The effects of mequitazine are comparable to those of other second-generation antihistamines, in that it causes mild driving impairment, particularly at higher doses.


Docosahexaenoic acid in cardiac metabolism and function.
The polyene fatty acid compostition of cardiac phospholipids is modified by a) dietary cod liver oil, b) norepinephrine, c) chronic administration of nicotine to animals fed a high cholesterol diet. Polyene fatty acids stimulate microsomal oxydation of epinephrine to cardiotoxic adrenochrome. Adrenochrome stimulates microsomal peroxydation or oxygenation of polyene fatty acids. There is an exponential relationship between docosahexaenoic acid of cardiac phospholipids and the heart rate.


Activity of citrinin metabolized by rat and human microsome fractions in clastogenicity and SCE assays on Chinese hamster V79-E cells.
The mycotoxin citrinin is a potent inducer of chromosomal aberrations in the clastogenicity assay on V79-E cells when metabolized by rat and human liver microsomes. Rat and human liver microsomes, standardized on protein content, activate citrinin at equal levels. 5 X 10(-4) M citrinin induces complex translocations in a high frequency as well as defects of chromosomal coiling. Higher concentrations are cytotoxic, lower ones are almost inactive. After metabolization of mycotoxin by rat-kidney microsomes or an S9 mix fraction containing rat liver and kidney microsomes, toxic effects predominate and chromosomal aberrations are diminished. Clastogenic citrinin concentrations do not induce an increase of SCE frequency. Although the mode of action of this mycotoxin on chromosomal structure remains obscure, possible explanations are discussed.


Two new imidazole alkaloids from Leucetta chagosensis sponge.
Chemical investigation of the sponge Leucetta chagosensis, has led to the isolation of two new imidazole alkaloids, methyldorimidazole (1), preclathridine B (2) along with the known compounds naamine E (3) and leucettamine C (4). The structures of the newly compounds (1 and 2) were elucidated by employing spectroscopic techniques ((1)H NMR, MS and UV). The structures of the known compounds 3 and 4 were determined by comparison of their (1)H NMR and Mass spectroscopic data with published values.


Enhancement of the repair of carcinogen-induced DNA damage in the hamster pancreas by dietary selenium.
We measured single strand breaks (SSB) in pancreas DNA produced by N-nitrosobis (2-oxopropyl)amine (BOP) in hamster fed purified diets containing added sodium selenite (Se) at 0.0, 0.1 and 5.0 ppm. There were fewer SSB in those given the 5.0 ppm Se diet throughout the experiment. One hour after dosing with BOP (20 mg/kg), there were 2.26 +/- 0.47, 2.83 +/- 0.43 and 1.74 +/- 0.43 SSB per 10(8) daltons (mean +/- S.E.M.) respectively in the three groups. The SSB were repaired faster in the 5.0 ppm Se-fed group. The approximate half-lives of the SSB were 33, 30 and 8 days, respectively. In the hamsters fed 5.0 ppm Se there was a small, statistically significant increase in pancreatic DNA synthesis. Autoradiographic analysis indicated that this was repair synthesis. In a second experiment, hamsters were fed one of the three diets prior to and for 2 days after administration of a single dose of BOP (20 mg/kg). They were then fed the 5.0 ppm Se diet for 5 days. The number of SSB was compared with those in hamsters fed their original diet for 7 days after BOP dosing. There was a statistically significant difference in the number of SSB in the hamsters fed 0.1 ppm Se before and for 2 days after BOP. In these hamsters there were 1.21 +/- 0.24 SSB per 10(8) daltons compared with 3.19 +/- 0.4 (mean +/- S.E.M.). These results suggest high levels of dietary Se stimulate the repair of carcinogen-induced DNA damage