Antimicrobial Susceptibility Profiles and Genetic Characteristics of Mycoplasma pneumoniae in Shanghai, China, from 2017 to 2019.
The current study investigated the recent genetic characteristics and antimicrobial susceptibility profiles of Mycoplasma pneumoniae (M. pneumoniae) in Shanghai, becoming a clinical reference for treating M. pneumoniae infection in Shanghai. Clinical strains were isolated from nasopharyngeal aspirates of the pediatric patients in Shanghai from 2017 to 2019. Nine antimicrobial agents of three antimicrobial classes macrolides, fluoroquinolones and tetracyclines, against M. pneumoniae isolates were investigated using the broth microdilution method. The mechanism of macrolide resistance was analyzed by evaluating the sequences of the 23S rRNA gene and the ribosomal protein genes L4 and L22. Molecular genotyping was undergone to classify the P1 subtypes and the multi-locus variable-number tandem-repeat analysis (MLVA) types. A total of 72 isolates were resistant to macrolides (MICs > 64 mg/L for erythromycin) based on the A2063G mutation in the 23S rRNA gene. These strains were susceptible to tetracyclines and fluoroquinolones. P1 type 1 (166/182, 91.2%) and MLVA type 4-5-7-2 (165/182, 90.7%) were the dominant subtypes. MLVA type was associated with the P1 subtypes. The distribution of the P1 subtypes and MLVA types did not change over time. The macrolide-resistant rate in P1 type 2 and MLVA type 3-5-6-2 strains were increased during the three-year study. The 5-loci MLVA typing scheme revealed the clonal expansion of MLVA type 3-4-5-7-2 strains which are macrolide-resistant in 2019. Macrolide resistance in M. pneumoniae in Shanghai is very high and is evolving among certain subtypes. Cautions should be taken for the possible clonal spreading of macrolide-resistant genotypes within this populated region.


Comparing the effectiveness of bimanual and unimanual mirror therapy in unilateral neglect after stroke: A pilot study.
Unilateral neglect in stroke patients is a major obstacle to rehabilitation, which is a great challenge for therapists. This study aimed to compare the effectiveness of bimanual mirror therapy (BMT) and unimanual mirror therapy (UMT), the two protocols of mirror therapy, for the reduction of the symptoms of unilateral neglect in stroke patients. Twenty-eight individuals were randomly assigned to the BMT or UMT groups. Both groups received mirror therapy for 30 minutes per day, 5 days a week, for a period of 4 weeks. The Star Cancelation Test (SCT), Line Bisection Test (LBT), Picture Scanning Test (PST), and Korean Catherine Bergego Scale (K-CBS) were used to measure the change in unilateral neglect, and the Korean version of the Modified Barthel Index (K-MBI) was used to evaluate activities of daily living (ADL). The results of SCT, LBT, PST, and K-CBS showed significant decreases in unilateral neglect in both groups (p < 0.05). K-MBI improved significantly in both groups (p < 0.05). There were significant differences between the two groups in the unilateral neglect tests (p < 0.05), but no significant difference in ADL evaluation (p > 0.05). Mirror therapy protocols can be applied to treat unilateral neglect in stroke patients. However, BMT may be more beneficial for reducing the symptoms of unilateral neglect.


Random-effects models for meta-analytic structural equation modeling: review, issues, and illustrations.
Meta-analytic structural equation modeling (MASEM) combines the techniques of meta-analysis and structural equation modeling for the purpose of synthesizing correlation or covariance matrices and fitting structural equation models on the pooled correlation or covariance matrix. Both fixed-effects and random-effects models can be defined in MASEM. Random-effects models are well known in conventional meta-analysis but are less studied in MASEM. The primary objective of this paper was to address issues related to random-effects models in MASEM. Specifically, we compared two different random-effects models in MASEM-correlation-based MASEM and parameter-based MASEM-and explored their strengths and limitations. Two examples were used to illustrate the similarities and differences between these models. We offered some practical guidelines for choosing between these two models. Future directions for research on random-effects models in MASEM were also discussed. Copyright © 2016 John Wiley & Sons, Ltd.


Transcatheter closure of atrial septal defect and patent foramen ovale with ASDOS device (a multi-institutional European trial).
A clinical trial was conducted to assess the feasibility, safety, and efficacy of the atrial septal defect (ASD) occlusion system for transcatheter closure of secundum ASD and patent foramen ovale (PFO) after episodes of cerebral embolism. Occlusion was attempted in 200 patients aged 1 to 74 years (mean 32). The procedure failed in 26 patients (13%); the device was retrieved through a catheter in 20 and through surgery in 6 patients. Procedure-related complications necessitating surgical removal of the device included device embolization in 2, device entrapment within the Chiari network in 1, frame fracture in 1, and perforation of atrial wall in 2. All 6 patients experienced an uneventful postoperative course. An additional 11 patients (6%) underwent surgical removal of the device during follow-up. There were 163 patients (81%) with an implanted ASD occlusion system at follow-up of from 6 to 36 months (mean 17). Thrombus formation around the device was detected by transesophageal echocardiography in 9 patients 1 to 4 weeks after implantation. One of these patients (who had a coagulation factor XII deficiency) suffered a cerebral thromboembolism. Late atrial wall perforation (5, 6, and 8 months after implantation) occurred in 3 adult patients. Infectious endocarditis developed in 2 adult patients (1%). No late device embolization and no atrioventricular valve injury occurred. An asymptomatic device frame fracture was found in 14% and frame deformity in 4% of all patients during the follow-up period of >230 patient-years. Immediately after closure, a moderate/large residual shunt remained in 8% and a small shunt in 29% of patients. After 1 year, a moderate/large shunt was present in 2% and a small one in 26% of patients. During a total follow-up of 49 patient-years, only 1 of 46 patients with PFO had a transient neurologic event after the closure. The study indicates that patients with centrally situated secundum ASD and those with PFO after cerebral embolism can be treated with this system with a high success rate and an acceptable morbidity.


Sheep liver cytosolic aldehyde dehydrogenase: the structure reveals the basis for the retinal specificity of class 1 aldehyde dehydrogenases.
. Enzymes of the aldehyde dehydrogenase family are required for the clearance of potentially toxic aldehydes, and are essential for the production of key metabolic regulators. The cytosolic, or class 1, aldehyde dehydrogenase (ALDH1) of higher vertebrates has an enhanced specificity for all-trans retinal, oxidising it to the powerful differentiation factor all-trans retinoic acid. Thus, ALDH1 is very likely to have a key role in vertebrate development. . The three-dimensional structure of sheep ALDH1 has been determined by X-ray crystallography to 2.35 A resolution. The overall tertiary and quaternary structures are very similar to those of bovine mitochondrial ALDH (ALDH2), but there are important differences in the entrance tunnel for the substrate. In the ALDH1 structure, the sidechain of the general base Glu268 is disordered and the NAD+ cofactor binds in two distinct modes. . The submicromolar Km of ALDH1 for all-trans retinal, and its 600-fold enhanced affinity for retinal compared to acetaldehyde, are explained by the size and shape of the substrate entrance tunnel in ALDH1. All-trans retinal fits into the active-site pocket of ALDH1, but not into the pocket of ALDH2. Two helices and one surface loop that line the tunnel are likely to have a key role in defining substrate specificity in the wider ALDH family. The relative sizes of the tunnels also suggest why the bulky alcohol aversive drug disulfiram reacts more rapidly with ALDH1 than ALDH2. The disorder of Glu268 and the observation that NAD+ binds in two distinct modes indicate that flexibility is a key facet of the enzyme reaction mechanism.


The views of people with a lived experience of deafness and the general public regarding genetic testing for deafness in the reproductive setting: A systematic review.
Genes associated with nonsyndromic hearing loss are commonly included in reproductive carrier screening panels, which are now routinely offered in preconception and prenatal care in many countries. However, there is debate whether hearing loss should be considered a medical condition appropriate for screening. This systematic review assessed research on opinions of those with a lived experience of deafness and the general public regarding genetic testing for deafness in the reproductive setting. Search of 5 online databases yielded 423 articles, 20 of which met inclusion criteria. We assessed the quality of each study, extracted data, and performed thematic analysis on qualitative studies. Most studies indicated interest in the use of prenatal diagnosis for deafness. However, there were mixed views, and sometimes strongly held views, expressed regarding the reproductive options that should be available to those with an increased chance of having a child with deafness. Studies were small, from a limited number of countries, and most were too old to include views regarding preimplantation genetic testing. There is a broad range of views regarding the use of reproductive options for deafness. Further research is essential to explore the benefits and harms of including nonsyndromic hearing loss genes in carrier screening.


Superhelicity of nucleosomal DNA changes its double-helical repeat.
Winding DNA in a superhelix can be considered a process consisting of two smooth deformations: bending and twisting. The extra twist angle introduced by winding DNA into the nucleosomal superhelix is calculated by means of the Crick formula to be -0.5 degrees per base pair (bp). This is equivalent to a change of -0.15 +/- 0.015 bp in the DNA double-helical repeat. Free DNA in solution is known to have a helical repeat of 10.55 +/- 0.1 bp. On the other hand, a weighted average of various estimates of the DNA repeat in the nucleosome is 10.38 +/- 0.02. The difference happens to be perfectly accounted for by the superhelicity of the nucleosomal DNA. This implies that the latter is essentially nonconstrained .


Clinical Implications of Heart Rate Control in Heart Failure With Atrial Fibrillation: Multi-Center Prospective Observation Registry (CODE-AF Registry).
Atrial fibrillation (AF) is treated by heart rate (HR) control. However, the optimal HR target in AF patients with heart failure (HF) remains unclear. To evaluate the clinical implication of the resting HR in AF patients with HF accompanied by preserved, mid-range, or reduced ejection fraction (HFpEF, HFmrEF, or HFrEF, respectively). Echocardiographic data from June 2016 to April 2020 in a prospective, multicenter, observational registry from 11,104 patients were analyzed. The follow-up duration was 2.2 years. The main outcome was composite of death and hospitalization. We categorized patients according to the HF type and resting HR: ≤ 60 bpm, 61-80 bpm, 81-110 bpm, and >110 bpm. A total of 1,421 patients were enrolled in the study: 582 in the HFpEF group, 506 in the HFmrEF group, and 333 in the HFrEF group. The patients had a mean age of 69 ± 11 years and consisted of 872 (61.4%) men. Primary endpoint rates among HFpEF patients with 60 < HR ≤ 110 bpm were lower than those with HR ≤ 60 bpm (61-80 bpm group: hazard ratio, 0.66; 95% CI, 0.46-0.94; p = 0.021; 81-110 bpm group: hazard ratio, 0.60; 95% CI, 0.40-0.90; p = 0.013). Especially, HFpEF patients with HR 81-110 bpm had a lower incidence of hospitalization caused by HF aggravation than those with other HR strata (HR ≤ 80bpm strata or HR >110 bpm strata). In HFmrEF and HFrEF patients, the survival rates did not differ significantly among patients in the three groups with HR ≤ 110 bpm. Moreover, the event rates increased significantly in HFmrEF patients with HR >110 bpm (hazard ratio, 1.91; 95% CI, 1.16-3.14, p = 0.011). In patients with AF and HFpEF, the resting HR has U-shaped associations with the overall primary endpoint. A lower or higher resting HR is associated with increased cardiovascular outcomes, especially in patients with HFpEF and AF.


Challenges in synthesis of real-world vaccine effects on meningococcal serogroup B disease for 4CMenB vaccine post-licensure effectiveness studies: A systematic review.
Real-world studies on vaccine effects are diverse in terms of objectives, study setting and design, data type and scope, and analysis methods. In this review, we describe and discuss four-component meningococcal serogroup B vaccine (4CMenB vaccine, Bexsero) real-world studies with the aim of synthesizing their findings with application of standard methods. We performed a systematic literature review of all real-world studies on 4CMenB vaccine effects on meningococcal serogroup B disease, with no restriction for population age, vaccination schedule and/or type of vaccine effect evaluated (vaccine effectiveness [VE] and vaccine impact [VI] outcomes) published since its licensure in 2013 (from January 2014 until July 2021) in PubMed, Cochrane and the grey literature. We then aimed to synthesize the findings of the identified studies through application of standard synthesis methods. According to reported criteria we retrieved five studies presenting estimates on 4CMenB vaccine effectiveness and impact. These studies showed great diversity in population, vaccination schedule and analysis methods mainly due to diversity in vaccine strategies and recommendations in the study settings. Directed by this diversity, no quantitative pooling methods to synthesize findings could be applied; instead we descriptively assessed study methods. We report VE estimates ranging from 59% to 94% and VI estimates ranging from 31% to 75%, representing diverse age groups, vaccination schedules and analysis methods. Both vaccine outcomes showed real-life effectiveness of 4CMenB vaccine despite differences in study methodologies and vaccination strategies. Based on appraisal of study methods, we highlighted the need for an adapted tool which facilitates synthesis of heterogenic real-world vaccine studies when quantitative pooling methods are not applicable.


Desmopressin is a transfusion sparing option to reverse platelet dysfunction in patients with severe traumatic brain injury.
Platelet dysfunction (PD) is an independent predictor of mortality in patients with severe traumatic brain injury (sTBI). Platelet transfusions (PLTs) have been shown to be an effective treatment strategy to reverse platelet inhibition. Their use is contingent on availability and may be associated with increased cost and transfusion-related complications, making desmopressin (DDAVP) attractive. We hypothesized that DDAVP would correct PD similarly to PLTs in patients with sTBI. This retrospective study evaluated all blunt trauma patients admitted to an urban, level 1 trauma center from July 2015 to October 2016 with sTBI (defined as head abbreviated injury scale [AIS] ≥3) and PD (defined as adenosine diphosphate [ADP] inhibition ≥60% on thromboelastography) and subsequently received treatment. Per our institutional practice, patients with sTBI and PD are transfused one unit of apheresis platelets to reverse inhibition. During a platelet shortage, we interchanged DDAVP for the initial treatment. Patients were classified as receiving DDAVP or PLT based on the initial treatment. A total of 57 patients were included (DDAVP, n = 23; PLT, n = 34). Patients who received DDAVP were more severely injured (injury severity score, 29 vs. 23; p = 0.045), but there was no difference in head AIS (4 vs. 4, p = 0.16). There was no difference between the two groups in admission platelet count (244 ± 68 × 10/μL vs. 265 ± 66 × 10/μL, p = 0.24) or other coagulation parameters such as prothrombin time, partial thromboplastin time, or international normalized ratio. Before treatment, both groups had similar ADP inhibition as measured by thromboelastography (ADP, 86% vs. 89%, p = 0.34). After treatment, both the DDAVP and PLT groups had similar correction of platelet ADP inhibition (p = 0.28). In patients with severe traumatic brain injury and PD, DDAVP may be an alternative to PLTs to correct PD. Therapeutic, level IV.


Sequential torsion of the uterine adnexa.
Sequential bilateral torsion of the uterine adnexa in a young girl led to right and, subsequently, left salpingo-oophorectomy. Acute lower abdominal pain in a young female patient, especially one who has had previous similar episodes, should alert the physician to the possible presence of adnexal torsion. If possible, surgical management of this condition should be conservative--that is, the blood supply should be restored to the adnexa and a viable tube or ovary should be preserved. Contralateral adnexal suspension should always be done, in an effort to prevent bilateral adnexal torsion and to preserve the reproductive potential in these young patients.


Dog filariosis in the Lazio region (Central Italy): first report on the presence of Dirofilaria repens.
Epidemiological investigations were carried out in the Lazio Region to assess the status of canine filariosis and to evaluate the actual risk for veterinary and medical public health. Since August 2001 to June 2003, a total of 972 canine blood samples, collected in public kennels and from private owners animals of the 5 Provinces of the Region, were tested. The presence of filarial parasites was evaluated by microscopy and bio-molecular techniques; the species identification was performed by means of the same diagnostic tools. A total of 17/972 (1.75%; 95%CI 1.06%-2.85%) blood samples were parasitized by D. repens,13 out them drawn by dogs resident in the Province of Roma, and 4 in the other provinces. Multivariate analysis was performed in order to evaluate the association between filariosis and risk factors. The origin from coastal territories seems to be a significant risk factor to acquire the infection. This is the first report of canine filariosis in the Lazio Region, where D. repens was before reported only in foxes. The risk of human zoonotic infection is stressed, and the absence of other filarial species is discussed.


The identification of metabolic disturbances in the prefrontal cortex of the chronic restraint stress rat model of depression.
Major depressive disorder, with serious impairment in cognitive and social functioning, is a complex psychiatric disorder characterized by pervasive and persistent low mood and a loss of interest or pleasure. However, the underlying molecular mechanisms of depression remain largely unknown. In this study, we used a non-targeted metabolomics approach based on gas chromatography-mass spectrometry of the prefrontal cortex in chronic restraint stress (CRS)-treated rats. CRS was induced in the stress group by restraining rats in a plastic restrainer for 6h every day. This stress paradigm continued for 21 days. Body weight measurement and behavior tests were applied, including the sucrose preference test for anhedonia, the forced swimming test for despair-like behavior, and open field test and the elevated plus-maze to test for anxiety-like behaviors in rats after CRS. Differentially expressed metabolites associated with CRS-treated rats were identified by combining multivariate and univariate statistical analysis and corrected for multiple testing using the Benjamini-Hochberg procedure. A heat map of differential metabolites was constructed using Matlab. Ingenuity Pathways Analysis was applied to identify the predicted pathways and biological functions relevant to the bio-molecules of interest. Our findings showed that CRS induces depression-like behaviors and not anxiety-like behaviors. Thirty-six metabolites were identified as potential depression biomarkers involved in amino acid metabolism, energy metabolism and lipid metabolism, as well as a disturbance in neurotransmitters. Consequently, this study provides useful insights into the molecular mechanisms of depression.


Sensorimotor modulation by botulinum toxin A in post-stroke arm spasticity: Passive hand movement.
In post-stroke spasticity, functional imaging may uncover modulation in the central sensorimotor networks associated with botulinum toxin type A (BoNT) therapy. Investigations were performed to localize brain activation changes in stroke patients treated with BoNT for upper limb spasticity using functional magnetic resonance imaging (fMRI). Seven ischemic stroke patients (4 females; mean age 58.86) with severe hand paralysis and notable spasticity were studied. Spasticity was scored according to the modified Ashworth scale (MAS). fMRI examination was performed 3 times: before (W0) and 4 (W4) and 11weeks (W11) after BoNT. The whole-brain fMRI data were acquired during paced repetitive passive movements of the plegic hand (flexion/extension at the wrist) alternating with rest. Voxel-by-voxel statistical analysis using the General Linear Model (GLM) implemented in FSL (v6.00)/FEAT yielded group session-wise statistical maps and paired between-session contrasts, thresholded at the corrected cluster-wise significance level of p<0.05. As expected, BoNT transiently lowered MAS scores at W4. Across all the sessions, fMRI activation of the ipsilesional sensorimotor cortex (M1, S1, and SMA) dominated. At W4, additional clusters transiently emerged bilaterally in the cerebellum, in the contralesional sensorimotor cortex, and in the contralesional occipital cortex. Paired contrasts demonstrated significant differences W4>W0 (bilateral cerebellum and contralesional occipital cortex) and W4>W11 (ipsilesional cerebellum and SMA). The remaining paired contrast (W0>W11) showed activation decreases mainly in the ipsilesional sensorimotor cortex (M1, S1, and SMA). The present study confirms the feasibility of using passive hand movements to map the cerebral sensorimotor networks in patients with post-stroke arm spasticity and demonstrates that BoNT-induced spasticity relief is associated with changes in task-induced central sensorimotor activation, likely mediated by an altered afferent drive from the spasticity-affected muscles.


Vesicoureteric reflux and tumor necrosis factor-alpha gene polymorphism.
To determine the role of tumor necrosis factor-alpha (TNF-alpha) gene polymorphism in promoting renal scarring among patients with vesicoureteric reflux (VUR). This genetic variant involves a guanosine to adenine transition at position -308, and this single-base polymorphism is associated with increased transcription of the TNF-alpha gene. Recent studies suggest that the TNF-alpha gene may be associated with predisposition to renal scarring. A total of 195 (51.8% females) patients with VUR demonstrated by voiding cystourethrogram were recruited, 126 of them with reflux nephropathy diagnosed by dimercaptosuccinic scan. The control group included 266 healthy individuals. Genotyping was performed by polymerase chain reaction and digestion with a restriction enzyme. Allele frequencies of -308G and -308A were 83.8% and 16.2%, respectively in patients with VUR and 88.9% and 11.1%, respectively in controls (P<0.05). No differences were found in genotype distribution related to presence/absence of renal scars. There was no relationship between TNF-alpha genotype and grade of VUR or the presence of proteinuria. Our data suggest that the TNF-alpha AA genotype is not associated with reflux nephropathy. The TNF-alpha-308A allele could be related to a higher susceptibility to VUR.


Controversies and Conundrums in Newborn Feeding.
Breastfeeding is the biologic norm for newborn feeding, and exclusive breastfeeding for the first 6 months of life is universally endorsed by leading global and national organizations. Despite these recommendations, many people do not meet their breastfeeding goals and controversies surrounding breastfeeding problems exist. Medical issues can present challenges for the clinician and parents to successfully meet desired feeding outcomes. There are studies evaluating these common controversies and medical conundrums, and clinicians should provide evidence-based recommendations when counseling families about newborn feeding.


Corrole-protein interactions in H-NOX and HasA.
Replacing the native porphyrin cofactor in haem proteins has led to the development of novel designer proteins for a variety of applications. In most cases, haem analogues bind in a way that is comparable to the iron porphyrin, but this is not necessarily the case for complexes bearing non-exchangeable ligands. This study probes how a P[double bond, length as m-dash]O corrole binds to functionally disparate hemoproteins: a haem-dependent oxygen sensor (H-NOX) and a haem-scavenging protein (HasA). The results demonstrate that the protein-cofactor interactions are distinct from the native, haem-bound holoprotein. In H-NOX, the P[double bond, length as m-dash]O unit primarily hydrogen bonds with the haem-ligating histidine (H102), rather than the hydrogen-bonding network that stabilises the Fe(ii)-O2 complex in the native protein. In the absence of H102, the protein is still able to bind the corrole, albeit at reduced levels. Molecular dynamics simulations were utilised to determine the flexibility of apo H-NOX and revealed the coupled motion of key residues necessary for corrole binding. In the case of HasA, the P[double bond, length as m-dash]O unit does not primarily interact with either the haem-ligating histidine (H32) or tyrosine (Y75). Instead, histidine 83, the hydrogen-bonding partner for Y75, is critical for P[double bond, length as m-dash]O corrole binding. The conformation of HasA is interrogated by site-specifically labelling the protein and exploiting Förster resonance energy transfer (FRET) to determine the dye-cofactor distance. HasA reconstituted with the P[double bond, length as m-dash]O corrole exhibits an extended, apo-like conformation. Together, these results demonstrate that non-natural cofactors can bind to proteins in unexpected ways and highlight the need to uncover these interactions for the further development of designer haem proteins.


Global reports of takotsubo (stress) cardiomyopathy following COVID-19 vaccination: A systematic review and meta-analysis.
Concerns have been raised recently about takotsubo cardiomyopathy (TCM) after receiving COVID-19 vaccines, particularly the messenger RNA (mRNA) vaccines. The goal of this study was to compile case reports to provide a comprehensive overview of takotsubo cardiomyopathy (TCM) associated with COVID-19 vaccines. A systematic literature search was conducted in PubMed, Scopus, Embase, Web of Science, and Google Scholar between 2020 and June 1, 2022. The study included individuals who developed cardiac takotsubo cardiomyopathy from receiving COVID-19 vaccinations. Ten studies, including 10 cases, participated in the current systematic review. The mean age was 61.8 years; 90 % were female, while 10 % were male. 80 % of the patients received the mRNA COVID-19 vaccine, while 20 % received other types. In addition, takotsubo cardiomyopathy (TCM) occurred in 50 % of patients receiving the first dose and another 40 % after the second dose of COVID-19 vaccines. Moreover, the mean number of days to the onset of symptoms was 2.62 days. All cases had an elevated troponin test and abnormal ECG findings. The left ventricular ejection fraction (LVEF) was lower than 50 % in 90 % of patients. In terms of the average length of hospital stay, 50 % stayed for 10.2 days, and all cases recovered from their symptoms. In conclusion, takotsubo (stress) cardiomyopathy (TCM) complications associated with COVID-19 vaccination are rare but can be life-threatening. Chest pain should be considered an alarming symptom, especially in those who have received the first and second doses of the COVID-19 vaccine.


High Resolution M-mode Evaluation of Jugular Vein Valves in Patients with Neurological and Neurosensory Disorders.
High prevalence of valve absence was found in the internal jugular vein (IJV) of healthy volunteers by means of M-mode high-resolution Echo Colour Doppler (ECD). However, the prevalence of valve in neurovascular disorders linked to Chronic Cerebrospinal Venous Insufficiency (CCSVI) is still unknown. A cohort of 83 Healthy Controls (HC), 71 Multiple Sclerosis (MS), 99 Inner Ear Disorders (IED) underwent ECD investigation of the IJV valve, including M-mode evaluation and related hemodynamics. The primary outcome measure was characterization of valve presence, morphology and motility, whereas the secondary outcome was the rate of flow alteration. Bilateral valve presence was found in 38% of HC, 58% of MS and 25% of IED, whereas, bilateral valve absence was recorded in 16% of HC, 10% of MS and 31% of IED (p<0.003). Bicuspid morphology was more prevalent in HC 56%, while monocusp was more prevalent in patients: 75% MS and 57% IED (p<0.0001). The main finding was the presence of mobile valve leaflets in 98% of HC, contrarily fixed valve leaflets were recorded in 82% of MS and in 41% of IED, p< 0.0001. Finally, by stratifying the entire cohort according to the presence of mobile and not mobile valve leaflets, normal monodirectional and phasic flow were commonly found in the mobile leaflets subgroup, p<0.0001. In patients with miscellaneous neurological disorders, a significant higher rate of defective valves was found with respect to HC. The latter condition is strongly associated to brain outflow abnormalities described in CCSVI condition.


Performance evaluation and users' perception of courtyards role in indoor areas of mediterranean social housing.
Cities confront two critical challenges: general overheating and inefficient use of energy resources within their housing buildings, both adversely affecting urban citizens' daily lives. To mitigate these issues, passive techniques offer promising solutions on enhancing building comfort levels from a sustainable approach. Although this energy efficiency of air-conditioning systems in buildings in warm climates has been extensively analysed, the influence of the microclimate of transitional spaces attached to them on this performance has not yet been properly assessed. Investigating the potential benefits of the implementation of courtyards within Seville's social housing infrastructure for passive conditioning purposes is one way of reducing this research gap. Furthermore, the study also includes the subjective perception of users' thermal well-being around these spaces and their own social relationship related to their use. The work relies on detailed data analyses carried out using DesignBuilder software to quantify the benefit effectively accrued from courtyard utilization. Concurrently, user surveys conducted help determine perceived thermal comfort aiding better configuration management and passive design strategies of urban social housing. Findings from monitoring and simulation reveal that courtyards work faultlessly as a highly effective and efficient passive cooling system whilst promoting energy efficiency up to 20,5%. Surveys confirmed these findings with data revealing significant improvements in thermal comforts perception inside courtyards and within indoor spaces adjacent to the courtyards. This research provides novel insights into how architects and urban managers might integrate passive strategies into future designs for optimizing comfort levels in social housing using courtyards as one possible environmental measure for achieving sustainability targets.


[The x-ray characteristics of the changes in the fallopian tubes of women with primary sterility who have had an appendectomy].
Using hysterosalpingography an attempt was made to classify the changes occurring in the uterine tubes of 114 women with primary sterility, undergone appendectomy in the past. It was established that changes in the tubes presented various character and included 2/5 of the material. There was direct dependence between appendectomy with complications and the gravity of the tubal factor.


Amyloidogenicity of peptides targeting diabetes and obesity.
Since the discovery of insulin, a century ago, the repertoire of therapeutic polypeptides targeting diabetes - and now also obesity - have increased substantially. The focus on quality has shifted from impure and unstable preparations of animal insulin to highly pure, homologous recombinant insulin, along with other peptide-based hormones and analogs such as amylin analogs (pramlintide, davalintide, cagrilintide), glucagon and glucagon-like peptide-1 receptor agonists (GLP-1, liraglutide, exenatide, semaglutide). Proper formulation, storage, manipulation and usage by professionals and patients are required in order to avoid agglomeration into high molecular weight products (HMWP), either amorphous or amyloid, which could result in potential loss of biological activity and short- or long-term immune reaction and silent inactivation. In this narrative review, we present perspective of the aggregation of therapeutic polypeptides used in diabetes and other metabolic diseases, covering the nature and mechanisms, analytical techniques, physical and chemical stability, strategies aimed to hamper the formation of HMWP, and perspectives on future biopharmaceutical developments.


[The complex course of a concussion and an exceptional diagnosis].
Concussion without loss of consciousness is common in every sport, but it occurs more often in high-impact sports such as handball or soccer. Concussion should be diagnosed early to protect the athlete. It is not easy to diagnose a concussion, but tests like the SCAT-5 can help. After the diagnosis, the athlete should undergo a return-to-sports procedure. Multiple concussions can cause long-term neurological deficits known as chronic traumatic encephalitis. If symptoms persist or clinical deterioration occurs, various differential diagnoses, some of them life threatening, have to be ruled out. In our case, a 29-year-old professional handball player was diagnosed with concussion and distortion of the cervical spine. Due to increasing symptoms and partly severe deterioration, the patient saw several doctors and underwent several diagnostic procedures. The correct diagnosis was made four weeks after the trauma. Today the player is playing handball on a professional basis again without any restriction.


Aquagenic Wrinkling of Skin: A Screening Test for Cystic Fibrosis.
To study the utility of aquagenic wrinkling as screening test for children with cystic fibrosis. Evaluation of diagnostic test. Pediatric Chest Clinic, and Pediatric Wards of a tertiary care hospital in New Delhi. Three groups (children with cystic fibrosis, carriers of cystic fibrosis, and controls). Time taken to develop aquagenic wrinkling was measured. The test was performed by asking the enrolled subject to put their one hand in water and was checked for development of wrinkling every minute, and a photograph was also taken every minute. A total of 64 children with cystic fibrosis, 64 controls and 64 carriers were enrolled in the study. Median (IQR) time to develop aquagenic wrinkling in the three groups was 2 (2.5,3) minutes, 4 (3,5) minutes and 8 (5,11) minutes, respectively. The optimal cut-off was calculated as 3 minutes by Receiver operating characteristic curve with a sensitivity and specificity for identification of children with cystic fibrosis as 81% and 57%, respectively. The area under curve was 76.5%. The 3 minute cut-off for development of aquagenic wrinkling was applied to 54 children referred for sweat test. 20 children had sweat chloride values of ≥60 mEq/l and diagnosed as cystic fibrosis. 15 of these developed aquagenic wrinkling at ≤3 minutes, giving a sensitivity of 75%. In places with no facility for sweat test, children with phenotype compatible with cystic fibrosis who develop aquagenic wrinkling in 3 minutes may be diagnosed as probable cystic fibrosis and referred for confirmation by sweat test.


Regression of left ventricular mass one year after aortic valve replacement for pure severe aortic stenosis.
The aim of the study was to quantify a 1-year change in left ventricular (LV) mass index (MI) and systolic LV function in 30 patients with pure severe aortic stenosis by means of serial 3-dimensional (3-D) echocardiography. To assess the completeness of LVMI regression after 1 year, we compared the postoperative mass of patients with mass values of 30 normotensive control subjects without a history of cardiac disease. Ejection fraction increased from 64 +/- 14% before surgery to 69 +/- 8% at follow-up (p = 0.067), and functional class improved from 2.9 +/- 0.5 to 1.4 +/- 0.5 (p <0.05), with improvement in each patient. During the same period, LVMI regressed by 23.4% (p <0.001). Postoperative LVMI was related to preoperative LVMI (r = 0.82; p <0.001) and baseline ejection fraction (r = -0.5; p = 0.009). LVMI regressed into the normal range in 64% of patients at follow-up. Patients achieving normal mass values did not differ with respect to patient gender, valve type, or valve size. Patients with reduced preoperative LV function had larger volumes (p <0.01), larger mass values (p <0.01), and a trend toward more mass regression (p = 0.062) than patients with normal preoperative function. Although ejection fraction improved after 1 year in all of these patients (p <0.03), they were less likely to achieve normal mass values at follow-up (p = 0.01). Regression of LVMI in patients with pure aortic stenosis is a positive event that occurs in each patient and that is associated with improvement in functional status. LVMI regressed into the normal range in most patients with normal preoperative function. Preoperative LV function, but not patient gender, valve type, or size, was related to normalization of LVMI at follow-up in this selected study population.


Comparison of laparoscopy and laparotomy in patients with endometrial cancer.
To evaluate results and feasibility of laparoscopic surgery in patients with stage I endometrial cancer. Prospective, nonrandomized study (Canadian Task Force classification II-I). University tertiary referring center. Fifty-one women with stage I endometrial cancer followed for 1 year. Laparoscopy (27 women) and open surgery (24). We recorded operating time, complications, and length of hospital stay. Operating time differed between groups, 87 versus 143 minutes for laparotomy and laparoscopy, respectively. Hospital stay was 6.2 days and 4.3 days, respectively. In the laparotomy group one patient experienced wound dehiscence and another had a vesicovaginal fistula requiring secondary repair. Complications in the laparoscopy group were one conversion to laparotomy because of bladder perforation and one case of septicemia that required laparotomy on the second postoperative day. Perioperative transfusions were administered to two women in the laparotomy group and none in the laparoscopy group. Laparoscopy may play an important role in treatment of early endometrial cancer. The procedure is difficult, however, and should be reserved to dedicated laparoscopists. It has low morbidity and, contrary to earlier recommendations, may be performed in older women with comorbidity.


What is the role of cerebrospinal fluid ferritin in the diagnosis of subarachnoid haemorrhage in computed tomography-negative patients?
Spectrophotometry of cerebrospinal fluid (CSF) for bilirubin is the recommended method for investigation in suspected cases of subarachnoid haemorrhage (SAH), when a computed tomography (CT) of the head is negative for blood. There is a potential need for a simpler alternative. Measurement of CSF ferritin might fulfil this need. We have measured ferritin in the CSF from 252 patients with suspected SAH who were negative on a CT of the head for blood, recruited on a consecutive intention to recruit basis from four centres. CSF spectrophotometry was performed on all samples. A positive outcome was taken as an aneurysm found on angiography that was treated or a discharge diagnosis of non-aneurysmal SAH. A final diagnosis of aneurysmal SAH was made in six patients, an arteriovenous malformation in one and non-aneurysmal SAH in nine. Receiver operating characteristic (ROC) analysis showed that at 6.4 microg/L, sensitivity, specificity, positive and negative predictive values were 1.0, 0.48, 0.12 and 1.0, respectively. At 12 microg/L, these values were 0.81, 0.91, 0.38 and 0.98, respectively. At an appropriate negative predictive value (1.0) for a rule-out test, ferritin has too low a specificity to function as a stand-alone test and we cannot recommend it as an initial screen to be followed by spectrophotometry.


Enhanced contrast of bacteriophage plaques in Salmonella with ferric ammonium citrate and sodium thiosulfate (FACST) and tetrazolium red (TZR).
Visualization of bacteriophage plaques may be enhanced by addition of ferric ammonium citrate and sodium thiosulfate (FACST) or 2,3,5-triphenyltetrazolium chloride (tetrazolium red, TZR) to the soft agar layer of a traditional bacteriophage plaque assay. Background color from these reagents improved contrast between clear plaques and turbid host lawns in trypticase soy agar (TSA) plates. Enhancement by FACST is based on reaction with hydrogen sulfide gas (H2S) produced by some strains of bacteria and was tested here using H2S+ and H2S- strains of Salmonella enterica subsp. enterica with a bacteriophage (Podoviridae) isolated from swine lagoon effluent. Only the H2S+ strain produced dark brown-black color in FACST-amended agar. Both strains showed bright pinkish-red color in TZR-amended agar. Color intensity for both reagents decreased with decreasing concentrations of the reagents. Contrast in FACST-amended plates appeared greater than that with TZR, but diminished after 12 h, while contrast in TZR-amended plates remained constant. At the concentrations tested, neither reagent affected plaque counts in the H2S+ strain. The FACST should be useful in bacteriophage plaque assays with H2S+ strains of Salmonella and other H2S+ bacteria.


Liver transplantation for biliary cysts: perioperative and long-term outcomes.
Biliary cysts (BC) is a rare indication for orthotopic liver transplantation (OLT). We queried the UNOS dataset to identify patients who underwent OLT for Caroli's disease (CD) and choledochal cysts (CC). All patients with BC (CD + CC) were compared to a cohort of patients transplanted for other indications. Patients with CC were also compared to those with CD. Cox proportional hazard model was performed to assess predictors of graft and patient survival. 261 patients underwent OLT for BC. Patients with BC had better pre-operative liver function compared to those transplanted for other indications. 5-year graft and patient survival were 72% and 81%, respectively, similar to those transplanted for other indications after matching. Patients with CC were younger and had increased preoperative cholestasis compared to those with CD. Donor age, race, and gender were predictors of poor graft and patient survival in patients transplanted for CC. Patients with BC have similar outcomes to those transplanted for other indications and more frequently require MELD score exception. In patients transplanted for choledochal cysts, female gender, donor age, and African-American race were independent predictors of poor survival. Pediatric patients transplanted for Caroli's disease had better survival compared to adults.


Fully analogue photonic reservoir computer.
Introduced a decade ago, reservoir computing is an efficient approach for signal processing. State of the art capabilities have already been demonstrated with both computer simulations and physical implementations. If photonic reservoir computing appears to be promising a solution for ultrafast nontrivial computing, all the implementations presented up to now require digital pre or post processing, which prevents them from exploiting their full potential, in particular in terms of processing speed. We address here the possibility to get rid simultaneously of both digital pre and post processing. The standalone fully analogue reservoir computer resulting from our endeavour is compared to previous experiments and only exhibits rather limited degradation of performances. Our experiment constitutes a proof of concept for standalone physical reservoir computers.


Shallow, non-pumped wells: a low-energy alternative for cleaning polluted groundwater.
This modeling study evaluated the capability of non-pumped wells with filter media for preventing contaminant plumes from migrating offsite. Linear configurations of non-pumped wells were compared to permeable reactive barriers in simulated shallow homogeneous and heterogeneous aquifers. While permeable reactive barriers enabled faster contaminant removal and shorter distances of contaminant travel, non-pumped wells also prevented offsite contaminant migration. Overall, results of this study suggest that discontinuous, linear configurations of non-pumped wells may be a viable alternative to much more costly permeable reactive barriers for preventing offsite contaminant travel in some shallow aquifers.


[Chronic broncopneumopathy and pneumoconiosis in workers employed in phosphoric acid production (author's transl)].
Thirty-five subjects employed in a phosphoric acid producing plant were studied by the authors. The investigation included: history, according to the C.E.C.A. questionnaire for chronic bronchitis and emphysema; physical examination, chest X-ray spirometry and lung diffusing capacity for carbon monoxide by the steady state method (DLCOSS). High prevalence of chronic bronchitis (45.7%), obstructive spirometric impairment (37.1%), and decreased values of DlcoSS (31.4%) were detected. Two subjects were found to be affected with p 1/0 and 7 with p 0/1 pneumoconiosis. Such findings were significantly related to the lenght of working activity as well as to dust and gaseous fluoride (hydrofluoric acid, hexafluorosilicic acid and silicon tetrafluoride) exposure.


Metastatic BRAF K601E-mutated melanoma reaches complete response to MEK inhibitor trametinib administered for over 36 months.
The BRAF K601E mutation occurs in 5% of patients with melanoma, and is the third most common type of BRAF mutation. However, treatment with BRAF and mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors is only approved in patients with BRAF V600-positive melanoma, and patients with K601E-mutated melanoma do not have access to such drugs. A female patient was diagnosed with high tumor burden metastatic melanoma harboring the BRAF K601E mutation. After chemotherapy failure, she underwent compassionate treatment with trametinib. Trametinib showed good activity and efficacy, with 48% shrinkage of a metastatic lymphadenopathy after 4 months' treatment. However, the patient reported treatment-related skin toxicity that required dosage reduction and a personalized intermittent trametinib dosing schedule. After over 36 months from the first trametinib administration, and resection of a metastatic lymphadenopathy, the patient experienced complete response. This case report shows that trametinib could be a valid therapeutic option in patients with metastatic melanoma harboring the rare BRAF K601E mutation.


E6AP, an E3 ubiquitin ligase negatively regulates granulopoiesis by targeting transcription factor C/EBPα for ubiquitin-mediated proteasome degradation.
CCAAT/enhancer-binding protein alpha (C/EBPα) is an important transcription factor involved in granulocytic differentiation. Here, for the first time we demonstrate that E6-associated protein (E6AP), an E3 ubiquitin ligase targets C/EBPα for ubiquitin-mediated proteasome degradation and thereby negatively modulates its functions. Wild-type E6AP promotes ubiquitin dependent proteasome degradation of C/EBPα, while catalytically inactive E6-associated protein having cysteine replaced with alanine at amino-acid position 843 (E6AP-C843A) rather stabilizes it. Further, these two proteins physically associate both in non-myeloid (overexpressed human embryonic kidney epithelium) and myeloid cells. We show that E6AP-mediated degradation of C/EBPα protein expression curtails its transactivation potential on its target genes. Noticeably, E6AP degrades both wild-type 42 kDa CCAAT-enhancer-binding protein alpha (p42C/EBPα) and mutant isoform 30 kDa CCAAT-enhancer-binding protein alpha (p30C/EBPα), this may explain perturbed p42C/EBPα/p30C/EBPα ratio often observed in acute myeloid leukemia (AML). We show that overexpression of catalytically inactive E6AP-C843A in C/EBPα inducible K562- p42C/EBPα-estrogen receptor (ER) cells inhibits β-estradiol (E2)-induced C/EBPα degradation leading to enhanced granulocytic differentiation. This enhanced granulocytic differentiation upon E2-induced activation of C/EBPα in C/EBPα stably transfected cells (β-estradiol inducible K562 cells stably expressing p42C/EBPα-ER (K562-C/EBPα-p42-ER)) was further substantiated by siE6AP-mediated knockdown of E6AP in both K562-C/EBPα-p42-ER and 32dcl3 (32D clone 3, a cell line widely used model for in vitro study of hematopoietic cell proliferation, differentiation, and apoptosis) cells. Taken together, our data suggest that E6AP targeted C/EBPα protein degradation may provide a possible explanation for both loss of expression and/or functional inactivation of C/EBPα often experienced in myeloid leukemia.


Spectrometric studies on stability of tenuazonic acid (TeA) solution in organic solvents.
The stability of tenuazonic acid solution at different temperatures and storage times was studied using methanol, methanol-water (8:2 v/v), benzene and benzene-acetonitrile (98:2 v/v) as solvents. Solutions were analysed by a spectrometric method TeA U.V.-spectrum was recorded. Results indicated that the optimum temperature for long-time storage period of tenuazonic acid solution in any solvent assayed is -20°C. Benzene and benzene-acetonitrile (98:2 v/v) could be advised to make tenuazonic acid solution which will be stored less than 2 months at 4°C. Methanol and methanolwater (8:2 v/v) are not recommended because a low stability of TeA solution in this solvents.


Effects of low salinity media on growth, condition, and gill ion transporter expression in juvenile Gulf killifish, Fundulus grandis.
The Gulf killifish, Fundulus grandis, is a euryhaline teleost which has important ecological roles in the brackish-water marshes of its native range as well as commercial value as live bait for saltwater anglers. Effects of osmoregulation on growth, survival, and body condition at 0.5, 5.0, 8.0 and 12.0‰ salinity were studied in F. grandis juveniles during a 12-week trial. Relative expression of genes encoding the ion transport proteins Na(+)/K(+)-ATPase (NKA), Na(+)/K(+)/2Cl(-) cotransporter(NKCC1), and cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel was analyzed. At 0.5‰, F. grandis showed depressed growth, body condition, and survival relative to higher salinities. NKA relative expression was elevated at 7 days post-transfer but decreased at later time points in fish held at 0.5‰ while other salinities produced no such increase. NKCC1, the isoform associated with expulsion of ions in saltwater, was downregulated from week 1 to week 3 at 0.5‰ while CFTR relative expression produced no significant results across time or salinity. Our results suggest that Gulf killifish have physiological difficulties with osmoregulation at a salinity of 0.5‰ and that this leads to reduced growth performance and survival while salinities in the 5.0-12.0‰ are adequate for normal function.


Mass spectrometry theory and application to adrenal diseases.
The diagnosis and management of adrenal diseases hinge upon accurate determination of hormone concentrations in blood and other body fluids. The advent of immunoassays for various steroid hormones has enabled the remarkable progress in adrenal disease over the last several decades, with some limitation. Sequential immunoassay of single analytes is a tedious process, which requires aliquots for each assay. In many complex adrenal diseases, including adrenal cancer and congenital adrenal hyperplasia, the patterns or ratios of multiple steroids rather than the value of any one steroid is more relevant. Although gas chromatography/mass spectrometry of urinary steroid metabolites has been employed to profile steroid production, throughput is slow, and availability is sparse. Recent generations of liquid chromatography-tandem mass spectrometry instruments (LC-MS/MS) provide the throughput and sensitivity required to measure many steroids simultaneously using small samples for commercial and research uses. Even in the best hands, however, LC-MS/MS suffers from limitations and requires diligent attention to detail during method development and implementation. This article reviews the theory, instrumentation principles and terminology, and practical application of mass spectrometry to clinical adrenal disorders.


Small bolus of esmolol effectively prevents sodium nitroprusside-induced reflex tachycardia without adversely affecting blood pressure.
Hypotensive anesthesia with sodium nitroprusside (SNP) often is associated with reflex tachycardia. The purpose of this study was to investigate whether a small bolus of esmolol could counteract SNP-induced reflex tachycardia and sympathetic activation without affecting blood pressure. Using a time-series study design, 27 healthy young patients scheduled for mandibular osteotomy were enrolled in this study. General anesthesia was maintained with 2% sevoflurane and 67% nitrous oxide in oxygen. SNP was administered to decrease the mean arterial pressure to 55 to 65 mm Hg. When heart rate (HR) increased reflexively to higher than 95 beats/min from SNP-induced hypotension, esmolol 0.5 mg/kg was given. Blood pressure and HR were measured, and the low-frequency component (0.04 to 0.15 Hz) of systolic blood pressure variability and high-frequency component (0.15 to 0.4 Hz) of HR variability were calculated to evaluate the autonomic condition. Data were analyzed using 1-way analysis of variance after multiple comparisons or t test. P < .05 was considered statistically significant. Of the 27 patients analyzed, 19 patients (70%) required esmolol. In these patients, SNP caused an increase in the low-frequency component of systolic blood pressure variability and a decrease in the high-frequency component of HR variability, leading to tachycardia (HR range, 95.9 ± 7.3 to 106.7 ± 7.4 beats/min; P < .001). Esmolol suppressed the effects of SNP on the low-frequency component of systolic blood pressure variability and high-frequency component of HR variability, resulting in an immediate decrease in HR to 86.9 ± 6.2 beats/min (P < .001), whereas mean arterial pressure remained unchanged. A small bolus of esmolol can suppress reflex tachycardia without significantly changing mean arterial pressure. Thus, esmolol restores the autonomic imbalance induced by SNP during hypotensive anesthesia.


Eliminating arterial pulsatile strain by external banding induces medial but not neointimal atrophy and apoptosis in the rabbit.
We have examined the role of vessel pulsation and wall tension on remodeling and intimal proliferation in the rabbit infrarenal abdominal aorta. A rigid perivascular polyethylene cuff was used to reduce vessel systolic diameter by 25%, producing a region of reduced circumferential strain. At 6 weeks postoperatively, reduced circumferential strain caused medial atrophy, with 45% reduction of medial area and 30% loss of medial smooth muscle cells. Apoptotic cell death was indicated by DNA fragmentation, propidium iodide staining, and cell morphology. Cuffing the aorta after balloon denudation produced medial atrophy but did not inhibit neointimal growth. At 1 week postoperatively, intimal thickness was slightly decreased in regions with reduced strain; however, intimal thickening in regions of reduced strain was not different from control segments at 3 weeks postoperatively (intimal area was 0.37 +/- 0.05 mm2 with reduced strain and 0.50 +/- 0.08 for controls, mean +/- SEM). We conclude that circumferential strain is a major factor controlling medial structure and cell number, whereas growth of the neointima after injury is not significantly affected by either reduced strain or extensive medial cell death. Vessel cuffing represents a new model of blood vessel remodeling in vivo that involves extensive smooth muscle cell apoptosis.


Synergistic activity of benzoyl peroxide and erythromycin.
Benzoyl peroxide (BP) is the most widely used topical agent for acne since its introduction in the 1960s. Concomitant topical treatment of BP and erythromycin is stated to be superior to BP alone. However, no synergistic activity has been found with this combination. Instead, such combination therapies are hypothesized to gain their efficacy by the coupled action of two effective treatments. The antibiotic kills all susceptible bacteria and the BP eliminates the resistant strains. The purpose was to compare radical production by BP alone and with various antibiotics to determine whether certain antibiotics increase radical formation by BP, as the antibacterial activity of BP may correlate with the amount of radicals it forms. Polymerization of tetraethylene glycol dimethacrylate was used as a test of BP radical activity. The results suggest that radical activity increases upon addition of certain antibiotics, such as erythromycin, to a solution of BP. Radical activity of BP in tetraethylene glycol dimethacrylate is increased when tested in consort with several antibiotics, such as the macrolides. We propose that the tertiary amines contained on certain antibiotics are responsible for catalysis of BP radical formation. If increased radical formation correlates with enhanced biological effect, then these data reveal the possibility of a biological synergism in mixtures of BP and antibiotics. An understanding of the mechanism of catalysis of BP radical formation by antibiotics may lead to the discovery of improved treatments for acne.


History of the concept of 'levels of evidence' and their current status in relation to primary prevention through lifestyle interventions.
Primary prevention is a major option to reduce the burden of chronic disease in populations. Because lifestyle interventions have proved to be effective, lifestyle recommendations including nutritional advice are made abundantly. However, both their credibility and their effectiveness are often considered not to be high. Therefore, scientific evidence should form the basis of recommendations and, as in clinical medicine, a rational approach should be followed for the evaluation of evidence. In this paper, the development and current concepts of 'levels of evidence' as they are applied in clinical medicine are outlined and their impact on evidence-based recommendations is discussed. Next, the question is raised as to how far the existing schemes are applicable to the evaluation of issues pertaining to primary prevention through lifestyle changes. Current schemes were developed mainly for clinical research questions and therefore place major emphasis on randomised controlled trials as the main and most convincing evidence in the evaluation process. These types of study are rarely available for lifestyle-related factors and might even not be feasible to obtain. Arguments are advanced to support the notion that a modification of currently existing 'levels of evidence' as developed for clinical research questions might be necessary. Thereby, one might be able to accommodate the specific aspects of evidence-related issues of recommendations for primary prevention through lifestyle changes, like dietary changes.


Spontaneous Clearance of Vertically Acquired Hepatitis C Infection: Implications for Testing and Treatment.
Current guidelines recommend that infants born to women with hepatitis C virus (HCV) viremia be screened for HCV antibody at age 18 months and, if positive, referred for RNA testing at 3 years to confirm chronic infection. This policy is based, in part, on analyses that suggest that 25%-40% of vertically acquired HCV infections clear spontaneously within 4-5 years. Data on 179 infants with HCV RNA and/or anti-HCV evidence of vertically acquired infection in 3 prospective European cohorts were investigated. Ages at clearance of infection were estimated taking account of interval censoring and delayed entry. We also investigated clearance in initially HCV RNA-negative infants in whom RNA was not detectable until after 6 weeks. Clearance rates were initially high then declined slowly. Apparently, many infections clear before they can be confirmed. An estimated 65.9% (95% credible interval [CrI], 50.1-81.6) of confirmed infections cleared by 5 years, at a median 12.4 (CrI, 7.1-18.9) months. If treatment were to begin at age 6 months, 18 months, or 3 years, at least 59.0% (CrI, 42.0-76.9), 39.7% (CrI, 17.9-65.9), and 20.9% (CrI, 4.6-44.8) of those treated would clear without treatment. In 7 (6.6%) confirmed infections, RNA was not detectable until after 6 weeks and not until after 6 months in 2 (1.9%). However, all such cases subsequently cleared. Most confirmed infection cleared by age 3 years. Treatment before age 3, if it was available, would avoid loss to follow-up but would result in substantial overtreatment.


Polyurethane leads: facts and controversy.
A comparison of polyurethane and silicone cardiac pacing leads is presented. In comparing mechanical and electrical properties, friction coefficient and hydrolytic stability, both are highly qualified for use as electrode sheaths. The occurrence of surface cracking of polyurethane leads is examined. Several suggestions are proposed for dealing with the manufacture of new leads, the technique of implantation, and the follow-up required for successful surveillance.


Challenges and Prospects for Providing Radiation Oncology Services in Africa.
There are considerable challenges to meeting the demands of the impending cancer crisis in Africa. These include a rising incidence of cancer and cancer-related deaths, equipment and maintenance costs, and deficits in human resources and training. Addressing these issues would be crucial to tackling the increasing burden of cancer on the continent. Innovations in technology and collaborative efforts within the global oncology community have created promising solutions for establishing quality cancer care in Africa and eradicating the massive disparities that currently exist. A multifaceted approach that establishes access to quality radiation oncology services is needed to curtail this alarming trend. In this article, we describe the current status of radiotherapy services in Africa, barriers and opportunities to improve this integral component of comprehensive cancer care.


Comparison of the impact of short (<1 year) and long-term (> or =1 year) clopidogrel use following percutaneous coronary intervention on mortality.
The optimal duration of clopidogrel administration after percutaneous coronary intervention (PCI) remains unknown. Clopidogrel is currently recommended for minimums of 1 and 12 months after bare-metal stent and drug-eluting stent implantation, respectively. To determine the impact of clopidogrel discontinuation 1 year after PCI, the outcomes of 530 consecutive patients who underwent PCI from January 2004 to July 2006, were free of cardiovascular events for 6 months after PCI, and had follow-up available for >12 months were examined. The outcomes of patients who received clopidogrel for > or =1 year were compared with those of patients who received it for <1 year. The mean age was 65 +/- 9 years. Patients often presented with acute coronary syndromes (57%), and 85% received drug-eluting stents. Clopidogrel was used for > or =1 year and for <1 year in 341 and 189 patients, respectively. During a mean follow-up period of 2.4 +/- 0.8 years, 40 patients (8%) died, 21 (4%) had acute myocardial infarctions, and 89 (17%) underwent repeat coronary revascularization. Compared with patients with clopidogrel administration for <1 year after PCI, those who received clopidogrel for > or =1 year had lower mortality (14.8% vs 3.5%, p <0.001). On multivariate analysis, clopidogrel use for > or =1 year was associated with lower mortality (hazard ratio 0.28, 95% confidence interval 0.14 to 0.59), independent of traditional cardiovascular risk factors, clinical presentation, and the use of drug-eluting stents. In conclusion, the use of clopidogrel for > or =1 year after PCI was associated with lower mortality.


MicroRNA expression profiling in alveolar macrophages of indigenous Chinese Tongcheng pigs infected with PRRSV in vivo.
Porcine respiratory and reproductive syndrome (PRRS), caused by PRRS virus (PRRSV), is one of the most serious infectious diseases in the swine industry worldwide. Indigenous Chinese Tongcheng (TC) pigs reportedly show strong resistance to PRRSV infection. The miRNA expression profiles of porcine alveolar macrophages (PAMs) of control TC pigs and those infected with PRRSV in vivo were analyzed by high-throughput sequencing to explore changes induced by infection. A total of 182 known miRNAs including 101 miRNA-5p and 81 miRNA-3p were identified with 23 up-regulated differentially expressed miRNAs (DEmiRNAs) and 25 down-regulated DEmiRNAs. Gene Ontology analysis showed that predicted target genes for the DEmiRNAs were enriched in immune response, transcription regulation, and cell death. The integrative analysis of mRNA and miRNA expression revealed that down-regulated methylation-related genes (DNMT1 and DNMT3b) were targeted by five up-regulated DEmiRNAs. Furthermore, 35 pairs of miRNAs (70 miRNAs) were co-expressed after PRRSV infection and six pairs were co-expressed differently. Our results describe miRNA expression profiles of TC pigs in response to PRRSV infection and lay a strong foundation for developing novel therapies to control PRRS in pigs.


Estimation of heritabilities and additive genetic correlations for reproduction traits in swine: insights for tropical commercial production systems using multiple trait animal models.
This study was to estimate heritabilities, additive genetic correlations, and phenotypic correlations between number of piglets born alive (NBA), litter birth weight (LTBW), number of piglets weaned (NPW) and litter weaning weight (LTWW) in different parities of Landrace (L), Yorkshire (Y), Landrace×Yorkshire (LY), and Yorkshire×Landrace (YL) sows in a commercial swine operation in Northern Thailand. Two models were utilized, a single trait repeatability model (RM) and a multiple trait animal model (MTM). The RM assumed reproductive records from different parities to be repeated values of the same trait, whereas the MTM assumed these records to be different traits. The two models accounted for the fixed effects of farrowing year-season, genetic group of the sow, heterosis, and age at first farrowing, and the random effects of sow, boar, and residual. Heritability estimates from RM were 0.02±0.01 for NBA, 0.10±0.01 for LTBW, 0.04±0.01 for NPW, and 0.11±0.01 for LTWW. Heritability estimates from MTM fluctuated across parities, ranging from 0.04±0.01 in parity 2 to 0.09±0.02 in parity 4 for NBA, 0.07±0.02 in parity 2 to 0.16±0.02 in parity 3 for LTBW, 0.04±0.02 in parity 4 to 0.08±0.01 in parity 1 for NPW, and 0.16±0.02 in parity 1 to 0.20±0.02 in parity 2 for LTWW. Additive genetic correlation estimates from MTM were also variable, ranging from 0.29±0.24 between NBA in parity 1 and NBA in parity 2 to 0.99±0.05 between LTWW in parity 3 and LTWW in parity 4. The findings of this study highlight the advantage of using MTM for the genetic improvement of reproductive traits in swine and contribute to the development of sustainable swine breeding programs in Thailand.


Neuromediators and defensive responses including tonic immobility (TI): Brain areas and circuits involved.
Serotonin, acetylcholine and GABA are the neuromediators most involved in tonic immobility (TI). TI duration, in fact, decreases in rabbits following systemic serotonin administration and in guinea pigs following serotonin microinjection administration into the amygdala owing to the activation of fear-related GABAergic inhibitory mechanisms. On the other hand, repeated TI inductions in rabbits and guinea pigs reduce brain serotonin turnover in several brain areas. Microinjections of the acetylcholine agonist carbachol into amygdala, hypothalamus and PAG increase TI duration and reduces other defensive responses to threatening stimuli in several animal species. The cholinergic and serotonergic systems exert different effects on TI in different regions of the PAG according to the receptors stimulated. Their combined action activates opioid-GABAergic neurons ultimately affecting TI duration. Mammals TI and human cataplexy are innate responses induced by different stimuli, although both characterized by deficiency in orexin, reduced muscle tone, normal jerk reflexes and preserved consciousness.


Altruistic sharing behavior in children: Role of theory of mind and inhibitory control.
This study aimed to assess altruistic sharing behavior in children aged 3 to 5, 6 to 8, and 9 to 11 years and to explore the involvement of potential cognitive mechanisms, namely theory of mind (ToM) and inhibitory control. A total of 158 children completed a dictator game with stickers as incentives. ToM was evaluated using a false belief task in preschoolers and the Strange Story Test in school-age children. Inhibitory control was assessed in preschoolers with the Day-Night task and in older children with the Stroop Color-Word Test. The result was that 48.10% of children aged 3 to 5 years decided to share, and the percentage rose significantly with increasing age. The difference in altruism level in children who decided to share among the three age groups was nonsignificant. These results suggest that mechanisms underlying the decision to share or not and altruistic behavior may be different. No significant linear relations were found between cognitive processes (i.e., ToM and inhibitory control) and sharing behavior. Surprisingly, 9- to 11-year-olds who shared 3 of 10 stickers performed worse in inhibitory control than did those who shared any other number of stickers. In conclusion, the proportion of children who decided to share, but not the level of altruism, increased with age. ToM was not involved in altruistic sharing, whereas inhibitory control may play a role when deciding how much to share.


MRI contrast enhancement of malignant liver tumours following successful cryoablation.
To assess the incidence and degree of MRI contrast enhancement in liver tumours following successful percutaneous cryoablation. Thirty-eight patients with liver metastases (n = 29) or hepatocellular carcinoma (n = 9) underwent percutaneous cryoablation of 45 tumours between March 2004 and June 2009, with complete ablation zone coverage of the tumour and no local recurrence on follow-up imaging to date (range 3-60 months, mean 16). Contrast-enhanced MRI was used to assess 45 tumours at 24 h, 32 tumours at 2-4 months, and 21 tumours at 5-7 months. Percentage of tumours with contrast enhancement was assessed using dynamic spoiled gradient echo T1-weighted images. Twenty-four hours post-cryoablation, 23 out of 45 tumours (51%) enhanced compared with 42 out of 43 (98%) pre-ablation (p < 0.001). Mean percentage tumour enhancement decreased from 157% (range 26-745%) pre-ablation, to 107% (27-260%) at 24 h (p = 0.003), and 43% (24-103%) at 2-4 months (p < 0.001). The incidence and degree of tumour enhancement decreased through 5-7 months. Unlike previously reported studies of radiofrequency ablation, successful cryoablation of liver tumours is often associated with persistent tumour contrast enhancement on MRI performed at 24 h and decreasing over 2-7 months. • Liver neoplasms often demonstrate MRI contrast enhancement following successful percutaneous cryoablation. • This differs from radiofrequency ablation techniques where contrast enhancement suggests residual tumour • This difference could potentially lead to important errors in follow up strategies.


[Effect of acupuncture serum on the number of osteclast cultured in vitro].
To observe effects of acupuncture serum of ovariectomized rats on the number of in vitro cultural osteoclast of newborn rats. Forty 12-month-old SD female rats were randomly divided into 4 groups: sham-operation control group, ovariectomized (model) group, acupuncture prevention group and acupuncture treatment group. Osteoclasts isolated from long bone of the newborn SD rat were cultured on 24-well culture plates with DMEM containing 10% the test serum. Forty-eight hours later, the osteoclasts were stained with tartrate resistant acid phosphatase (TRAP) and the number of TRAP-positive multinucleated cells were counted. The number of TRAP-positive multinucleated cells in the model group significantly increased as compared with the sham-operation control group (P < 0.01), and in the acupuncture prevention group and the acupuncture treatment group significantly declined compared with the model group (P < 0.05). Acupuncture serum can equally reduce the number of osteoclasts in the two group.


Functional outcome of prolonged refractory status epilepticus.
To characterize etiology, clinical course and outcomes of patients in prolonged refractory status epilepticus (PRSE) and looking for prognostic factors. Retrospective study conducted in patients hospitalized from January 1, 2001 to December 31, 2011 in 19 polyvalent intensive care units in French university and general hospitals. Patients were adults with a generalized convulsive refractory status epilepticus that lasted more than seven days, despite treatment including an anesthetic drug and mechanical ventilation. Patients with anoxic encephalopathy were excluded. Follow-up phone call was used to determine functional outcome using modified Rankin Scale (mRS) with mRS 0-3 defining good and mRS 4-6 poor outcome. 78 patients (35 female) were included. Median age was 57 years. Causes of status epilepticus were various, mainly including prior epilepsy (14.1%), CNS infection (12.8%), and stroke (12.8%). No etiology was found in 27 (34.6%) patients. PRSE was considered controlled in only 53 (67.9%) patients after a median duration of 17 (IQR 12-26) days. The median length of ICU stay was 28 (19-48) days. Forty-one (52.5%) patients died in the ICU, 26 from multiple organ failure, 8 from care withdrawal, 2 from sudden cardiac arrest, 1 from brain death and 4 from unknown causes. PRSE was previously resolved in 20 patients who died in the ICU. At one-year follow-up, there were 12 patients with good outcome and 58 with poor outcome and 8 lost of follow-up. On multivariate analysis, only vasopressor use was a predictor of poor outcome (OR 6.54; 95%CI 1.09-39.29; p = 0.04). Poor outcome was observed in about 80% of this population of PRSE. Most patients died from systemic complications linked to their ICU stay. Some patients can recover satisfactorily over time though we did not identify any robust factor of good outcome.


Differential Stability of Aurein 1.2 Pores in Model Membranes of Two Probiotic Strains.
Aurein 1.2 is an antimicrobial peptide from the skin secretion of an Australian frog. In the previous experimental work, we reported a differential action of aurein 1.2 on two probiotic strains Lactobacillus delbrueckii subsp. bulgaricus (CIDCA 331) and Lactobacillus delbrueckii subsp. lactis (CIDCA 133). The differences found were attributed to the bilayer compositions. Cell cultures and CIDCA 331-derived liposomes showed higher susceptibility than the ones derived from the CIDCA 133 strain, leading to content leakage and structural disruption. Here, we used molecular dynamics simulations to explore these systems at the atomistic level. We hypothesize that if the antimicrobial peptides organized themselves to form a pore, it will be more stable in membranes that emulate the CIDCA 331 strain than in those of the CIDCA 133 strain. To test this hypothesis, we simulated preassembled aurein 1.2 pores embedded into bilayer models that emulate the two probiotic strains. It was found that the general behavior of the systems depends on the composition of the membrane rather than the preassemble system characteristics. Overall, it was observed that aurein 1.2 pores are more stable in the CIDCA 331 model membranes. This fact coincides with the high susceptibility of this strain against antimicrobial peptide. In contrast, in the case of the CIDCA 133 model membranes, peptides migrate to the water-lipid interphase, the pore shrinks, and the transport of water through the pore is reduced. The tendency of glycolipids to make hydrogen bonds with peptides destabilizes the pore structures. This feature is observed to a lesser extent in CIDCA 331 due to the presence of anionic lipids. Glycolipid transverse diffusion (flip-flop) between monolayers occurs in the pore surface region in all the cases considered. These findings expand our understanding of the antimicrobial peptide resistance properties of probiotic strains.


Physical ergonomics in low-back pain prevention.
This paper reviews the current state of knowledge regarding the tools used in evaluating the workplace and worker in hopes of preventing low-back injury. Information regarding the current state of expenditure and trends toward ergonomic intervention are discussed. Acknowledgment is made of the increasing shift of responsibility from Compensation Boards to industry, and a review proactive preventative strategies and medical knowledge is included. Current ergonomic assessment tools are reviewed and the role of the Physical Ergonomist is introduced. Suggestions are made regarding the value of current and future approaches in prevention and direction of research.


'Scirrhous' type hepatocellular carcinomas: a special reference to expression of cytokeratin 7 and hepatocyte paraffin 1.
'Scirrhous' hepatocellular carcinoma (scirrhous HCC) is extremely rare and its characteristics remain unclear. We investigated the clinicopathological and immunohistochemical features of scirrhous HCC, compared with those of ordinary hepatocellular carcinoma (ordinary HCC). We compared the clinicopathological and immunohistochemical features of 20 resected cases of scirrhous HCC with those of 69 resected cases of ordinary HCC. Scirrhous HCC was characterized by its gross and histological findings, such as a higher proportion of contiguous multinodular type tumours, the absence of a complete fibrous capsule around the tumour, the absence of tumour necrosis and highly preserved portal tracts in the tumour. The immunohistochemical results revealed a significantly higher expression of cytokeratin 7 and a significantly lower expression of hepatocyte paraffin 1 in scirrhous HCC than in ordinary HCC (P<0.0001, respectively). There were no significant differences in proliferative activity and survival curves between the patients with scirrhous HCC and those with ordinary HCC. Scirrhous HCC has several particular gross, histological and immunohistochemical features. In particular, we would like to emphasize the greater immunohistochemical expression of cytokeratin 7 and lower expression of hepatocyte paraffin 1 in scirrhous HCC than in ordinary HCC.


Frequency, Severity, and Duration of Autonomic Symptoms in Patients of Prodromal Dementia with Lewy Bodies.
Autonomic dysfunction is supportive clinical feature for diagnosis of prodromal dementia with Lewy bodies (DLB). To compare the features of autonomic symptoms in patients with mild cognitive impairment (MCI) due to Lewy bodies (MCI-LB) and Alzheimer's disease (MCI-AD). Autonomic symptoms were evaluated in the MCI-LB and MCI-AD patients using the Scales for Outcomes in Parkinson's disease for autonomic symptoms (SCOPA-AUT). Thirty patients with MCI-LB and 90 patients with MCI-AD were recruited. The frequency of autonomic dysfunction was higher in patients with MCI-LB compared to the MCI-AD patients (80% versus 54.4%, p = 0.013) and the gastrointestinal symptoms were predominant (73.3% versus 35.6%, p < 0.001). Salivation, constipation, incontinence, incomplete emptying, lightheadedness when standing up or standing for some times, diurnal or nocturnal hyperhidrosis, and sexual dysfunction were more severe and protracted in the MCI-LB group compared to the MCI-AD group. The MCI-LB patients showed higher frequency and severity, as well as longer duration of autonomic symptoms compared to the MCI-AD group. These symptoms can facilitate early diagnosis of patients with DLB.


Mucin 2 (MUC2) promoter characterization: an overview.
Transgenic livestock have been studied with a well-known interest in improving quantitative and qualitative traits. In order to direct heterologous gene expression, it is indispensable to identify and characterize a promoter suitable for directing the expression of the gene of interest (GOI) in a tissue-specific way. The gastrointestinal tract is a desirable target for gene expression in several mammalian models. Throughout the surface of the intestinal epithelium, there is an intricate polymer network, formed by gel-forming mucins (especially MUC2 and MUC5AC, of which MUC2 is the major one), which plays a protective role due to the formation of a physical, chemical and immunological barrier between the organism and the environment. The characterization of the gel-forming mucins is difficult because of their large size and repetitive DNA sequences and domains. The main mucin in the small and large intestine, mucin 2 (MUC2), is expressed specifically in goblet cells. MUC2 plays an important role in intestinal homeostasis and its disruption is associated with several diseases and carcinomas. This mucin is also an important marker for elucidating mechanisms that regulate differentiation of the secretory cell lineage. This review presents the state of the art of MUC2 promoter structure and functional characterization.


Cancer-associated fibroblasts: Mediators of head and neck tumor microenvironment remodeling.
Cancer-associated fibroblasts (CAFs) are involved in critical aspects of head and neck squamous cell carcinoma (HNSCC) pathogenesis, such as the formation of a tumor-permissive extracellular matrix structure, angiogenesis, or immune and metabolic reprogramming of the tumor microenvironment (TME), with implications for metastasis and resistance to radiotherapy and chemotherapy. The pleiotropic effect of CAFs in TME is likely to reflect the heterogeneity and plasticity of their population, with context-dependent effects on carcinogenesis. The specific properties of CAFs provide many targetable molecules that could play an important role in the future therapy of HNSCC. In this review article, we will focus on the role of CAFs in the TME of HNSCC tumors. We will also discuss clinically relevant agents targeting CAFs, their signals, and signaling pathways, which are activated by CAFs in cancer cells, with the potential for repurposing for HNSCC therapy.


Why insect energy budgets do not balance.
(1) Energy budgets are based upon the equation: C=P+R+FU, where C=consumption, P=production, R=respiration and FU=egesta. In studies of insect energetics, where all four parameters have been measured, the completed budget rarely balances. This can often be traced to inaccuracy in the R term which, when measured with a respirometer (R m ), is almost invariably less than when calculated as C-P-FU(=R c ). (2) The R c·R mEmphasis>/-1 values of 'wild' insects (av. 2.58) are consistently larger than those of 'laboratory' insects (av. 1.25). (3) Suggestions that incorrect oxycalorific equivalents, caused by inappropriate RQ values, result in large inaccuracies in R m are shown to be invalid. (4) The possibility that the C term in the energy budgets of phytophagous insects has been miscalculated because of a failure to account for leaf respiration is discounted because it is equally possible, at least in properly conducted experiments, for leaves to gain weight by photosynthesis. Furthermore, this factor cannot account for imbalances in the budgets of nonphytophages. (5) The gut contents of phytophagous insects can weigh as much as the gut-free body. Failures to account for this factor lead to over-estimates of P. (6) It is concluded that there is little reason to doubt evidence published elsewhere that 'flask-effects' are the major cause of the discrepancy between R m and R c .


Interlaboratory reproducibility of the immunocytochemical assessment of oestrogen and progesterone receptors and proliferative activity in fine needle aspiration of breast cancer.
The purpose of this study was to establish the interlaboratory reproducibility of immunocytochemical analysis of oestrogen (ER) and progesterone (PR) expression and Mib1 growth fraction on fine needle aspiration (FNA) smears. A set of 44 immunostained slides for ER, PR and Mib1 were randomly selected from the archives of the Center for the Study and Prevention of Cancer (CSPO) of Florence, Italy, and submitted for reading to 6 Italian laboratories. The generalized kappa statistic was used as an indicator of agreement among the six laboratories. A good correlation for ER and PR was evident. For Mib1 the results showed some discrepancies. In addition to adequate standardization of procedures, these data confirm that the reliability of the immunocytochemistry is strictly linked to accurate analysis of the results.


Structural and antitumoral characteristic dataset of the chitosan based magnetic nanocomposite.
The evaluation on the characteristic dataset and figures presented here, are related to our latest research data entitled "Fabrication of chitosan based magnetic nanocomposite by click reaction strategy; evaluation of nanometric and Cytotoxic characteristics" [1]. FTIR, Vibrating Sample Magnetometer (VSM) measurements, Xray diffraction (XRD) information and the resulted figures for structural confirmation of the prepared chitosan based nanocomposite are presented in this article. The morphological changes of the Fibroblast, Saos, MCF7 and Hela cell lines after treatment with the mention compound were displayed. The additional adsorption data for the synthesized nanobiocomposite were also demonstrated with graphs.


Agenesis of the pulmonary artery: an unusual cause of dyspnea in pregnancy.
A pregnancy complicated by dyspnea was associated with agenesis of the right pulmonary artery. The clinical characteristics of the agenesis of the pulmonary artery along with the differential diagnosis from pulmonary embolus are discussed.


Sexual comparisons in immune ability, survival and parasite intensity in two damselfly species.
Recent evolutionary studies have suggested that females have a more robust immune system than males. Using two damselfly species (Hetaerina americana and Argia tezpi), we tested if females produced higher immune responses (as phenoloxidase and hydrolytic enzymes), had a higher survival (using a nylon implant inserted in the abdomen and measuring survival after 24h) and fewer parasites (gregarines and water mites) than males. We also tested whether immune differences should emerge in different body areas (thorax vs. abdomen) within each sex with the prediction that only females will differ with the abdomen having a higher immune response than their thorax since the former area, for ecological and physiological reasons, may be a target zone for increased immune investment. Animals were adults of approximately the same age. In both species, females were more immunocompetent than males, but only in H. americana females were immune responses greater in the abdomen than in the thorax. However, there were no differences in survival and parasite intensity or the probability of being parasitised between the sexes in either of the two species. Thus, this study lends partial support to the principle that females are better at defending than males despite the null difference in parasitism and survival.


Neuroendocrine carcinoma of the extrahepatic biliary tract with positive immunostaining for gastrin-releasing peptide: report of a case.
We report herein the first documented case of gastrin-releasing peptide-positive neuroendocrine (NE) carcinoma of the extrahepatic biliary tract. An invasive tumor measuring 2.5 x 1.5 cm was located in the confluence portion of the cystic duct in a 70-year-old Japanese man. Histologically, the tumor was found to be composed of small polygonal cells which formed a solid and trabecular structure, and the frequencies of both mitoses and small necrotic areas were dominant. The tumor cells were immunoreactive to the NE markers chromogranin-A and neuron-specific enolase, as well as to carcinoembryonic antigen and gastrin-releasing peptide. Although a few cases of gastrin-releasing peptide-positive small-cell lung carcinoma have been documented, there have been no reports of gastrin-releasing peptide-positive NE carcinoma occurring in the gastrointestinal tract. We consider our case not merely to be of pathological interest, but also to have clinical and therapeutic implications.


Adjuncts to posterior endodontic surgery.
Adjuncts to posterior endodontic surgery include fiberoptics, high-torque handpieces, and optical magnification. These current technologies allow the clinician to expand and amplify his surgical techniques. The patient can now have the benefit of treatment options not available previously.


Raising the intracellular level of inositol 1,4,5-trisphosphate changes plasma membrane ion transport in characean algae.
Inositol 1,4,5-trisphosphate (InsP3) was introduced into the cytoplasm of characean algae in two different ways: (i) by iontophoretic injection into cytoplasm-enriched fragments from Chara and (ii) by adding InsP3 to the permeabilization medium of locally permeabilized cells of Nitella. In both systems this operation induced a depolarization of the membrane potential, ranging from a few mV to sequences of action potentials. The effect of InsP3 on locally permeabilized Nitella cells was abolished when InsP3 was added together with 30 mM EGTA. When inositol 1,4-bisphosphate or myo-inositol were substituted for InsP3 in this system, there was no change in the membrane potential. On the other hand, increasing the free Ca2+ concentration in the permeabilization medium induced, in a similar fashion to InsP3, action potentials. Similarities between InsP3 and Ca2+ action were also observed upon injection into Chara fragments. Both injections increased an inward current. In the first few seconds after injection the current/voltage characteristics of the InsP3-induced current resembled those of the Ca2(+)-sensitive current. Subsequently, differences between the InsP3- and Ca2(+)-induced phenomena became apparent in that the InsP3-induced current continued to increase while the Ca2(+)-induced current declined, returning to the resting level. Our results suggest that these plant cells contain an InsP3 sensitive system that, under experimental conditions, is able to affect membrane transport via an increase in cytoplasmic free Ca2+.


Polymorphisms for interleukin-4 (IL-4) -590 promoter, IL-4 intron3, and tumor necrosis factor alpha -308 promoter: non-association with endometriosis.
Interleukin-4 (IL-4) is a cytokine with anti-inflammatory properties. Tumor necrosis factor alpha (TNF-alpha), a pluripotent proinflammatory cytokine, plays an important role in the process of numerous inflammatory and autoimmune diseases. We aimed to investigate whether gene polymorphisms for the IL-4 -590 promoter, IL-4 intron3 and TNFalpha -308 promoter could be used as markers of susceptibility in endometriosis. The subjects, 226 premenopausal Taiwan Chinese women with surgically diagnosed endometriosis and nonendometriosis, were divided into two groups: 1) endometriosis (n = 120) and 2) nonendometriosis (n = 106). Polymorphisms for the IL-4 -590 promoter, IL-4 intron3, and TNFalpha -308 G-to-A promoter were detected by polymerase chain reaction (PCR). Genotypes and allelic frequencies for these gene polymorphisms in both groups were compared. We observed no significant differences in genotype distribution and allele frequency of the IL-4 -590 promoter, IL-4 intron3, and TNFalpha gene polymorphism between both groups. The proportions of the -590*C homozygote/heterozygote/-590* T homozygote for the IL-4 promoter in both groups were 1.6/31.6/66.6% in group 1, and 5.8/33.0/61.2% in group 2. The proportions of the RP1 homozygote/heterozygote/RP2 homozygote for IL-4 intron3 in both groups were 62.5/34.1/2.5% (group 1), and 64.1/32.0/3.9% (group 2). The proportions of -308*A homozygote/heterozygote/-308*G homozygote for the TNFalpha promoter in both groups were 7.5/20.8/71.7% (group 1), and 7.5/17/75.5% (group 2). We concluded that there is no association between endometriosis and the IL-4 and TNFalpha gene polymorphisms. The IL-4 -590 promoter, IL-4 intron3, and TNFalpha -308 G-to-A polymorphisms are not useful markers for predicting susceptibility to endometriosis.


Interactions between a new class of eukaryotic antimicrobial agents and isolated rat liver mitochondria.
Members of a newly discovered class of eukaryotic antimicrobial peptides are shown to release respiratory control in isolated rat-liver mitochondria. They also dissipate the membrane potential and inhibit respiration. The uncoupling activity of the peptides decreases with time probably due to the presence of proteases in the mitochondrial preparation. Quinine and Mg2+ reduce the activity of the peptides. The nature of the dependence of the respiratory rate on the concentration of added peptides suggests that they are active in a multimeric form, consistent with the formation of a channel across the inner mitochondrial membrane. The channel allows passage of sucrose.


Retinal photoreceptors of Syrian hamsters undergo oxidative stress during streptozotocin-induced diabetes.
The aim of this study was to verify whether retinal photoreceptors, like other tissues, are subject to oxidative stress during diabetes. Oxidative stress was monitored by the oxidation of preloaded dehydrorhodamine 123 into fluorescent rhodamine 123, during a period of intense illumination of isolated rod retinal receptor cells. These were obtained from 22 Syrian hamsters injected with streptozotocin (50 mg/kg body weight., intraperitoneal route) 90 days before the study began. Eleven hamsters were treated daily with melatonin (0.4 mg/kg body wt., per os), an antioxidant synthesized within photoreceptors. Isolated photoreceptors were bathed on the stage of a Leitz Orthoplan microscope, where the fluorescent lamp also served as the light stimulus (485 nm). Fluorescence irradiance was measured by photometry and stored in a personal computer for further analysis. The light-induced oxidant production greatly decreased and was also delayed in the streptozotocin-injected hamsters compared with the control hamsters matched for age. Similar effects were obtained in control photoreceptors after 40 min incubation with 2-2'-azobis (2-amidinopropane) dihydrochloride, a potent lipoperoxidation inducer. The effect of melatonin was to partially restore the light-induced fluorescence response. The depression of the light-induced oxidative response in diabetic photoreceptors could be ascribed to a hyperglycaemia-induced background of oxidative stress whereby the light-oxidizable substrate is actually lowered. Melatonin induces a larger fluorescence response during illumination, probably as a consequence of its antioxidant effect during diabetes, which would provide more oxidizable lipids.


Autoantibodies against human ventricular myosin in sera of patients with acute and chronic myocarditis.
The present study investigated the presence of antimyosin autoantibodies in sera of patients with myocarditis and in three control groups: healthy blood donors, patients with alcoholic cardiomyopathy and patients with other cardiac diseases. An increasing body of evidence indicates that in the course of myocarditis, autoimmunologic mechanisms may play a pathogenetic role. Animal studies with Coxsackie B3 virus-induced murine myocarditis could demonstrate the appearance of circulating autoantibodies against cardiac myosin. Sera were analyzed by enzyme-linked immunosorbent assay (ELISA) and Western blot with human left ventricular myosin as antigen. Seventeen (42%) of 40 serum samples from patients with myocarditis showed antibody-binding against myosin, whereas only 1 (2.5%) of 39 samples from healthy blood donors and 9 (21%) of 43 samples from patients with other cardiac diseases showed autoantibodies against myosin (p < 0.05 vs. myocarditis). In sera from patients with alcoholic cardiomyopathy (n = 12), no antibodies against human ventricular myosin could be detected. In Western blots, the antimyosin antibodies in patients with myocarditis bound to the myosin heavy chain. Using protein-A sepharose chromatography, it could be shown that the antimyosin autoantibodies are of the immunoglobulin G (IgG) type. In ELISA, the antimyosin autoantibodies bind equally to myosin prepared from either cardiac or skeletal muscle, respectively. These results demonstrate the presence of autoantibodies against human ventricular myosin in patients with myocarditis. The prevalence of these autoantibodies is significantly higher in patients with myocarditis than in patients with other cardiac diseases. No organ specificity of the autoantibodies could be detected.