The emerging role of epigenetic mechanisms in insect defense against pathogens.
Insects resist infection by natural selection that favors the survival and reproduction of the fittest phenotypes. Although the genetic mechanisms mediating the evolution of insect resistance have been investigated, little is known about the contribution of epigenetic mechanisms. Gene expression in response to a pathogen selection pressure is regulated by different mechanisms affecting chromatin plasticity. Whether transgenerational inheritance of genome-wide epigenetic marks contributes to the heritable manifestation of insect resistance is presently debated. Here, we review the latest works on the contributions of chromatin remodeling to insect immunity and adaptation to pathogens. We highlight DNA methylation, histone acetylation, and microRNAs in mediating the transgenerational inherited transcriptional reprogramming of defense-related gene expression and the evolution of insect resistance.


Distribution of aqueous-deficient and evaporative dry eye in a clinic-based patient cohort: a retrospective study.
To evaluate in a general clinic-based cohort of patients with dry eye disease (DED) the distribution of patients with aqueous-deficient or evaporative subtype of DED. Schirmer tests and meibomian gland dysfunction (MGD) (Foulks-Bron scoring) were evaluated in both eyes of 299 normal subjects and DED patients (218 women and 81 men) across 10 sites in the European Union and the United States. Using the more severe measurement of the 2 eyes, subjects were considered to have pure aqueous-deficient dry eye (ADDE) with Schirmer values of <7 mm and MGD grades of ≤5. Patients were classified as purely evaporative dry eye with MGD grades of >5 and Schirmer values of ≥7 mm. Subjects were placed into the mixed (hybrid) category if they exhibited both a low Schirmer value of <7 and evidence of MGD with a grade >5. Of the 224 subjects classified with DED using an objective, composite, disease severity scale, 159 were classified into 1 of 3 categories: 79 were classified with only MGD, whereas only 23 were classified as purely aqueous deficient, and 57 showed evidence of both MGD and aqueous deficiency. Overall, 86% of these qualified DED patients demonstrated signs of MGD. The remaining 65 patients showed evidence of DED through other clinical signs, without overt evidence of MGD or ADDE, possibly because of the inherent variability of these signs. The proportion of subjects exhibiting signs of evaporative dry eye resulting from MGD far outweighs that of subjects with pure ADDE in a general clinic-based patient cohort.


Comparison of relapse and long-term survival between pylorus-preserving and Whipple pancreaticoduodenectomy in periampullary cancer.
Whether long-term survival and type of recurrence in periampullary cancer are influenced by the type of surgical procedure or not is still obscure. The purpose of this review was to analyze the results at a single institution. Between 1982 and 1996, 113 consecutive patients with either distal bile duct or ampullary cancers underwent either pylorus-preserving pancreaticoduodenectomy (PPPD) or the Whipple procedure. The median follow-up was 30 months (range 12 to 150). Patient records were reviewed to determine type of recurrence and survival. In distal bile duct or ampullary cancers, comparison of actuarial survival curves between PPPD and the Whipple operation revealed no significant differences. Even in node-positive patients, the 5-year survival rates did not differ significantly between those undergoing PPPD or the Whipple operation. Tumor recurrence was not correlated with the operative method, although among types of tumor recurrence, the rate of blood-borne metastasis was higher in distal bile duct or ampullary cancers. PPPD is an acceptable alternative to the Whipple procedure in the treatment of periampullary cancer. Long-term survival and type of recurrence were not influenced by these types of surgical procedures.


[CD1 molecules--mechanisms of lipid antigens presentation].
This review summarizes the status of our knowledge on the structure, expression and function of CD1 proteins. An endosomal and non-endosomal pathways of CD1 antigen presentation are also described.


Sequence Variants of Uncertain Significance: What to Do When Genetic Test Results Are Not Definitive.
Clinical genetic testing for cancer predisposition syndromes often identifies DNA changes whose effects cannot be interpreted easily. These changes, often referred to as variants of uncertain significance (VUS), are not useful for clinical management. In contrast with clearly pathogenic mutations, VUS do not firmly diagnose a specific syndrome at the molecular level and cannot be used to identify with certainty which relatives are mutation carriers and which relatives are free of the syndrome. This article discusses the approach to evaluating VUS and how clinicians can play a key role in advancing the field to benefit all patients.


Immunodetection of the p21-ras products in human normal and preneoplastic tissues and solid tumors: a review.
Immunohistochemical detection of p21-ras to identify and characterize preneoplastic or neoplastic lesions in human tissues is reviewed. Information concerning the commercially available antibodies is presented. Antibodies DWP, Ras-10, Y13-259, YA6-172, NCC-001, and NCC-004 are fully documented with respect to their behavior in appropriate specificity tests and appear to be reliable reagents. After reviewing the data we have identified three groups of tissues or organs with respect to positive immunostaining for p21-ras as the significant criterion of malignancy. These three groups comprise (1) tissues for which no definite conclusion could be drawn (colon, lung, bladder, ovary, and neural and odontogenic tissues) despite occasional claims to the contrary, (2) tissues for which conclusions were negative (pancreas and stomach), and (3) tissues for which p21-ras staining positively discriminated malignant from normal tissues (liver, uterus, and salivary gland). Immunohistochemically detectable levels of products from a mutated ras gene could be demonstrated in a fraction of the samples from colon, lung, and bladder carcinomas, as well as in some histologically normal tissues adjacent to a colon carcinoma. The possibility that a higher relative intensity of the immunostaining reaction for p21-ras might discriminate malignant tissues from normal tissues or benign lesions in breast, pancreas, stomach, lung, uterus, or thyroid samples is suggested. Further studies now appear warranted and a strategy is proposed to validate the conclusions reached thus far.


Decarboxylative 1,4-Addition of α-Oxocarboxylic Acids with Michael Acceptors Enabled by Photoredox Catalysis.
Enabled by iridium photoredox catalysis, 2-oxo-2-(hetero)arylacetic acids were decarboxylatively added to various Michael acceptors including α,β-unsaturated ester, ketone, amide, aldehyde, nitrile, and sulfone at room temperature. The reaction presents a new type of acyl Michael addition using stable and easily accessible carboxylic acid to formally generate acyl anion through photoredox-catalyzed radical decarboxylation.


Refined distribution of myelinated trigeminal proprioceptive nerve fibres in Mueller's muscle as the mechanoreceptors to induce involuntary reflexive contraction of the levator and frontalis muscles.
Stretching of mechanoreceptors in Mueller's muscle induces reflexive contraction of not only the levator muscle but also the frontalis muscle as two different eyelid-opening muscles. Previously, we reported that fine neural myelinated structures, acting as mechanoreceptors, were found in the proximal Mueller's muscle. Since there is a risk of misunderstanding that the middle and distal Mueller's muscle does not contain mechanoreceptors and can be invalidated or resected, the accurate distribution of myelinated trigeminal proprioceptive nerve fibres as mechanoreceptors in Mueller's muscle was refined horizontally in this study. We explored 10 whole Mueller's muscles between the levator muscle and the tarsus of the upper eyelids obtained from five Japanese cadavers. The specimens were serially sliced along the horizontal plane and stained with HE, S-100 protein to determine the presence of Schwann cells, and smooth muscle actin antibody to determine the presence of Mueller's smooth muscle fibres. Although all myelinated nerve fibres in the intermuscular connective tissues among the sympathetically innervated Mueller's multi-unit smooth muscle fibres may not correspond to the proprioceptive nerve fibres, the nerve bundles consisting of multiple myelinated nerve fibres were well distributed in the proximal Mueller's muscle, and single myelinated nerve fibres were well distributed in the middle and distal Mueller's muscle. We believe that the mechanoreceptors in Mueller's muscle consist of myelinated proprioceptive nerve fibres with nerve endings possibly attached to collagen fibres in the intermuscular connective tissues present among Mueller's smooth muscle fibres. As the myelinated nerve fibres innervate the middle and distal Mueller's muscle to a greater extent than those in the proximal Mueller's muscle, the former may be more important as mechanoreceptors than the latter and should not be invalidated or excised during surgery for treatment of blepharoptosis to prevent reduction of reflexive contraction of the levator and frontalis muscles.


Influence of Monascus purpureus BD-M-4 on the physicochemical properties, proteolysis and volatile compounds of surface mould-ripened cheese.
The effect of adjunct culture Monascus purpureus BD-M-4 on the physicochemical, proteolytic, and lipolytic properties of surface mold-ripened cheese were evaluated. During the maturation of Monascus-fermented cheese, the total microbiota count and the content of soluble nitrogen increased steadily, whereas the total protein content showed no significant difference. Moreover, a 17-fold increase in total free amino acids was observed in Monascus-fermented cheese. The use of adjunct culture M. purpureus BD-M-4 in the production of surface-ripened cheeses did not show a significant effect on the total fat content in the ripening period, nor did it change the lipolysis of cheese during ripening. Compared to 52 volatile compounds of the control cheese, a total of 62 compounds were detected in M. purpureus-fermented cheese, including 16 acids, 16 ketones, 11 alcohols, 5 aldehydes, 11 esters, and 3 unclassified compounds.


[The anatomy and pathology of the brain stem demonstrated by thin slice CT cisternography].
We demonstrated normal CT anatomy of the brain stem and adjacent structures using thin slice CT cisternography. Reducing the streak artifact caused by bony structures, thin slice CT cisternography can visualize the detailed features of the brain stem and its pathological changes. In addition, reconstructed images are also useful in diagnosis.


Prostaglandins E2, F2 alpha, 6-keto-F1 alpha and thromboxane B2 levels in carrageenin-induced inflammatory exudates in the rat air-pouch granuloma.
Levels of PGE2, PGF2 alpha, PGI2 (measured as 6-keto-PGF1 alpha), and thromboxane B2 were determined in rat inflammatory excuates induced 1, 3, and 7 days after carrageenin injection into air-pouch granuloma. The PGE2 and 6-keto-PGF1 alpha levels found in the exudate could not account for the differences in PGE2-like activity as measured by biologic and serologic methods.


Transcriptome analysis identification of A-to-I RNA editing in granulosa cells associated with PCOS.
Polycystic ovary syndrome (PCOS) is a complex, multifactor disorder in women of reproductive age worldwide. Although RNA editing may contribute to a variety of diseases, its role in PCOS remains unclear. A discovery RNA-Seq dataset was obtained from the NCBI Gene Expression Omnibus database of granulosa cells from women with PCOS and women without PCOS (controls). A validation RNA-Seq dataset downloaded from the European Nucleotide Archive Databank was used to validate differential editing. Transcriptome-wide investigation was conducted to analyze adenosine-to-inosine (A-to-I) RNA editing in PCOS and control samples. A total of 17,395 high-confidence A-to-I RNA editing sites were identified in 3,644 genes in all GC samples. As for differential RNA editing, there were 545 differential RNA editing (DRE) sites in 259 genes with Nucleoporin 43 (NUP43), Retinoblastoma Binding Protein 4 (RBBP4), and leckstrin homology-like domain family A member 1 (PHLDA) showing the most significant three 3'-untranslated region (3'UTR) editing. Furthermore, we identified 20 DRE sites that demonstrated a significant correlation between editing levels and gene expression levels. Notably, MIR193b-365a Host Gene (MIR193BHG) and Hook Microtubule Tethering Protein 3 (HOOK3) exhibited significant differential expression between PCOS and controls. Functional enrichment analysis showed that these 259 differentially edited genes were mainly related to apoptosis and necroptosis pathways. RNA binding protein (RBP) analysis revealed that RNA Binding Motif Protein 45 (RBM45) was predicted as the most frequent RBP binding with RNA editing sites. Additionally, we observed a correlation between editing levels of differential editing sites and the expression level of the RNA editing enzyme Adenosine Deaminase RNA Specific B1 (ADARB1). Moreover, the existence of 55 common differentially edited genes and nine differential editing sites were confirmed in the validation dataset. Our current study highlighted the potential role of RNA editing in the pathophysiology of PCOS as an epigenetic process. These findings could provide valuable insights into the development of more targeted and effective treatment options for PCOS.


FUSKEY, an interactive computer key to commonFusarium species.
An interactive computer key to 17 commonFusarium species has been developed. The key, FUSKEY, uses morphological, physiological and chemical criteria and is running on a PC (MS-DOS structured) using easy obtainable software.


[Acute mesenteric ischemia-An overview and recommendations (S2k analogous) of the World Society of Emergency Surgery].
Acute mesenteric ischemia is a severe illness, which if untreated, rapidly leads to a critical condition with sepsis, multiple organ failure and death in affected patients. The diagnosis and initiation of treatment of acute mesenteric ischemia should be performed as early and expeditiously as possible and follows the principle of the shortest possible time to reperfusion. Otherwise, the outcome of the patient rapidly deteriorates. The treatment algorithm should be adapted to the pathogenesis of the ischemia, the clinical condition and symptoms of the patients. With clinical signs of peritonitis, intestinal gangrene must be assumed and the abdomen should be surgically explored to detect and treat possible foci of sepsis at an early stage. The treatment of acute mesenteric ischemia should always be performed by an interdisciplinary team with all surgical and interventional options for intestinal revascularization as well as comprehensive intensive care medicine according to the standards of the Intestinal Stroke Center described in the literature. A short duration to revascularization and treatment in this interdisciplinary concept improves the outcome of patients with acute mesenteric ischemia. The World Society of Emergency Surgery provides expert consensus-based recommendations for the diagnosis and treatment of acute mesenteric ischemia; however, there is still a significant lack of broad high-quality evidence for this critical illness. Recommendations of the German specialist societies are urgently needed to ensure appropriate care, from the initial diagnostics to treatment and aftercare, for patients with suspected mesenteric ischemia in this country.


Gating of homeostatic regulation of intrinsic excitability produces cryptic long-term storage of prior perturbations.
Neurons and neuronal circuits must maintain their function throughout the life of the organism despite changing environments. Previous theoretical and experimental work suggests that neurons monitor their activity using intracellular calcium concentrations to regulate their intrinsic excitability. Models with multiple sensors can distinguish among different patterns of activity, but previous work using models with multiple sensors produced instabilities that lead the models' conductances to oscillate and then to grow without bound and diverge. We now introduce a nonlinear degradation term that explicitly prevents the maximal conductances to grow beyond a bound. We combine the sensors' signals into a master feedback signal that can be used to modulate the timescale of conductance evolution. Effectively, this means that the negative feedback can be gated on and off according to how far the neuron is from its target. The modified model recovers from multiple perturbations. Interestingly, depolarizing the models to the same membrane potential with current injection or with simulated high extracellular K+ produces different changes in conductances, arguing that caution must be used in interpreting manipulations that serve as a proxy for increased neuronal activity. Finally, these models accrue traces of prior perturbations that are not visible in their control activity after perturbation but that shape their responses to subsequent perturbations. These cryptic or hidden changes may provide insight into disorders such as posttraumatic stress disorder that only become visible in response to specific perturbations.


Is the treatment of Enterobius vermicularis co-infection necessary to eradicate Dientamoeba fragilis infection?
Dientamoeba fragilis is a pathogenic protozoan of the human gastrointestinal tract with a worldwide distribution, which has emerged as an important and misdiagnosed cause of chronic gastrointestinal illnesses such as diarrhea and 'irritable-bowel-like' gastrointestinal disease. Very little research has been conducted on the use of suitable antimicrobial compounds. Furthermore, higher rates of co-infection with Enterobius vermicularis have been described, suggesting that E. vermicularis could influence the treatment of D. fragilis-infected patients. To study this, the treatment of E. vermicularis and D. fragilis co-infected patients was evaluated. Forty-nine patients with a D. fragilis infection, including 25 (51.0%) patients co-infected with E. vermicularis, were studied. All of them were treated with metronidazole. Patients with E. vermicularis co-infection and/or an E. vermicularis-positive case in the family were treated with mebendazole. Metronidazole treatment failure was significantly more frequent in patients with E. vermicularis co-infection and in patients with children in the family. Co-infection with E. vermicularis may act as a factor favoring D. fragilis infection by preventing eradication measures. This suggests that both parasites should be treated simultaneously.


ACE2, ACE, DPPIV, PREP and CAT L enzymatic activities in COVID-19: imbalance of ACE2/ACE ratio and potential RAAS dysregulation in severe cases.
Circulating enzymatic activity and RAAS regulation in severe cases of COVID-19 remains unclear, therefore we measured the serum activity of several proteases as potential targets to control the SARS-CoV-2 infection. 152 patients with COVID-19-like symptoms were grouped according to the severity of symptoms (COVID-19 negative, mild, moderate and severe). Serum samples of COVID-19 patients and controls were subjected to biochemical analysis and enzymatic assays of ACE2, ACE, DPPIV, PREP and CAT L. One-way ANOVA and multivariate logistic regression analysis were used. Statistical significance was accepted at p < 0.05. We detected a positive correlation among comorbidities, higher C-reactive protein (CRP) and D-dimer levels with disease severity. Enzymatic assays revealed an increase in serum ACE2 and CAT L activities in severe COVID-19 patients, while ACE, DPPIV and PREP activities were significantly reduced. Notably, analysis of ACE2/ACE activity ratio suggests a possible imbalance of ANG II/ANG(1-7) ratio, in a positive association with the disease severity. Our findings reveal a correlation between proteases activity and the severity of COVID-19. These enzymes together contribute to the activation of pro-inflammatory pathways, trigger a systemic activation of inflammatory mediators, leading to a RAAS dysregulation and generating a significant damage in several organs, contributing to poor outcomes of severe cases.


Oxygenated verticillene derivatives from Bursera suntui.
Medium polarity fractions of the hexane extracts of the stems of Bursera suntui afforded six previously known (1-6) and four hitherto unknown verticillane derivatives: (1S,3Z,7S,8S,11S,12S)-(+)-7,8-epoxyverticill-3-en-12,20-diol (7), (1S,3Z,7S,8S,11S,12S)-(+)-7,8-epoxyverticill-3-en-12,20-diol 20-acetate (8), (1S,3Z,7S,11S,12S)-(+)-verticilla-3,8(19)-dien-7,12,20-triol (9), and (1S,3Z,7S,11S,12S)-(+)-verticilla-3,8(19)-dien-7,12,20-triol 20-acetate (10). Acetylation of 9 and 10 yielded (1S,3Z,7S,11S,12S)-(+)-verticilla-3,8(19)-dien-7,12,20-triol 7,20-diacetate (11), while hydrolysis of 8 gave 7. The structures and stereochemistry of 7-11 were established by spectroscopic analyses, particularly by 1D and 2D NMR spectra and HRESIMS. The conformational preferences of 7-11 were studied by molecular mechanics modelling employing the Monte Carlo protocol followed by B3LYP/DGDZVP DFT calculation, thus supporting the observed (1)H NMR NOESY cross peaks.


Id and development.
During development, it is obvious that enormous multiplication and diversification of cells is required to build a body plan from a single fertilized egg and that these two processes, proliferation and differentiation, must be coordinated properly. Id proteins, negative regulators of basic helix-loop-helix transcription factors, possess the ability to inhibit differentiation and to stimulate proliferation, and are useful molecules for investigating the mechanisms regulating development. In the past few years, our understanding of the roles of Id proteins has been substantially enhanced by the detailed investigation of genetically modified animals. The data have indicated that the functions of Id proteins in vivo are functionally related to those revealed by earlier work in cell culture systems. However, unexpected organs and cell types have also been found to require Id proteins for their normal development. This review looks at the advances made in our understanding of the in vivo functions of Id proteins. The topics discussed include neurogenesis, natural killer cell development, lymphoid organogenesis, mammary gland development and spermatogenesis.


Bone metastases and immunotherapy in patients with advanced non-small-cell lung cancer.
Bone metastases (BoM) are a negative prognostic factor in non-small-cell lung cancer (NSCLC). Beyond its supportive role, bone is a hematopoietic organ actively regulating immune system. We hypothesized that BoM may influence sensitivity to immunotherapy. Pretreated non-squamous (cohort A) and squamous (cohort B) NSCLCs included in the Italian Expanded Access Program were evaluated for nivolumab efficacy according to BoM. Cohort A accounted for 1588 patients with non-squamous NSCLC, including 626 (39%) with (BoM+) and 962 (61%) without BoM (BoM-). Cohort B accounted for 371 patients with squamous histology including 120 BoM+ (32%) and 251 (68%) BoM- cases. BoM+ had lower overall response rate (ORR; Cohort A: 12% versus 23%, p < 0.0001; Cohort B: 13% versus 22%, p = 0.04), shorter progression free survival (PFS; Cohort A: 3.0 versus 4.0 months, p < 0.0001; Cohort B: 2.7 versus 5.2 months, p < 0.0001) and overall survival (OS; Cohort A: 7.4 versus 15.3 months, p < 0.0001; Cohort B: 5.0 versus 10.9 months, p < 0.0001). Moreover, BoM negatively affected outcome irrespective of performance status (PS; OS in both cohorts: p < 0.0001) and liver metastases (OS cohort A: p < 0.0001; OS Cohort B: p = 0.48). At multivariate analysis, BoM independently associated with higher risk of death (cohort A: HR 1.50; cohort B: HR 1.78). BoM impairs immunotherapy efficacy. Accurate bone staging should be included in clinical trials with immunotherapy.


Therapeutic failure with chloroquine in Plasmodium falciparum infections; possibility of high grade resistance.
Three case reports of falciparum malaria not responding to standard chloroquine therapy and necessitating the use of alternative antimalarial drugs for clinical improvement, are documented. In vitro drug sensitivity tests and chloroquine assays were not carried out to conclusively exclude drug failure. However, the clinical course and the persistence of parasitaemia on thick blood film monitoring were suggestive of high grade chloroquine resistance. Such patients require clinical vigilance and the timely use of alternative antimalarials. When rapid clearance of parasitaemia is required quinine is the drug of choice. In malarial chemotherapy it is mandatory that strict therapeutic criteria be followed, to safeguard the efficacy of chloroquine as well as to prevent abuse of alternative drugs. In this context, the availability of thick blood films and in vitro drug sensitivity testing facilities in hospitals would be useful to clinicians.


Finite-time adaptive sliding mode control for high-precision tracking of piezo-actuated stages.
Piezo-actuated stages are widely used in nanopositioning applications. However, they not only have inherent static hysteresis characteristics but also have dynamic rate-dependent hysteresis nonlinearity. Therefore, to address dynamic hysteresis nonlinearity and uncertainty in the model parameters, an adaptive switching-gain sliding mode controller with a proportional-integral-derivative surface is designed. In particular, the combination of Bouc-Wen model and second-order linear system is used to describe the dynamic hysteresis process. To improve the robustness and reduce chattering in the sliding mode control method, an adaptive switching-gain is added to the controller without knowing in advance the upper bound of uncertainties. Finite-time convergence conditions of the closed-loop system are also analyzed. Finally, the proposed control method is implemented in real time on an ARM experimental platform. Comparative experimental results demonstrate excellent tracking performance and robustness. The dynamic hysteresis characteristics are suppressed effectively, and this result provides a powerful reference for engineering applications.


Meal patterning in the treatment of bulimia nervosa.
This study examined the relationship between changes in meal and snack consumption and eating disorder behaviors in a treatment sample of bulimic adults. Eighty adults with bulimia nervosa (BN) were randomized to one of two treatments. Meal and snack consumption, binge eating frequency, and purging behavior frequency were assessed at baseline, end-of-treatment, and at four month follow-up using the Eating Disorder Examination (EDE). Generalized linear models indicated that increased consumption of evening meals over the course of treatment was related to a significant decrease in the rate of binge eating and purging at four month follow-up; these results remained significant when controlling for changes in depression over the course of treatment. The findings support the importance of focusing efforts on developing a pattern of regular evening meal consumption among individuals in the treatment of BN.


Chest wall configuration in supine man: wakefulness and sleep.
We measured the anteroposterior and lateral diameter of the rib cage (RC), the anteroposterior diameter of the abdomen (ABD) and the cranio caudal abdominal dimension during breathing in supine posture, in order to analyze the shape of the chest wall in both awake and sleep conditions. By comparing the active breath holding and relaxation curves, it appeared that during activity of the respiratory muscles the RC is both expanded and distorted at the highest volumes and mainly distorted at the lowest volumes. During sleep the abdominal protrusion is smaller and the lateral sides of the rib cage expand more than during wakefulness. This might explain the higher rib cage motion during sleep found by some authors who measured the rib cage circumference and not confirmed by others who measured only its anteroposterior diameter. The motion of the rib cage is similar during sleep and wakefulness, its lateral parts leading the anteroposterior ones, showing that the pattern of motion of the rib cage is not affected by the different activation of the respiratory muscles. The possibility of a distorsion within the front part of the rib cage has been also discussed.


[Spinal ultrasound study in pediatrics: its role in the diagnosis of spinal cord malformations and postoperative conditions].
The advent of new technologies in neurosurgery has made it necessary to create a current algorithm of the radiation diagnosis of congenital spinal cord diseases in children in the pre- and postoperative period. Due to the efficiency and low cost of a study, ultrasound diagnosis becomes an important element of this algorithm.


Synthesis and properties of CS x F y thin films deposited by reactive magnetron sputtering in an Ar/SF6 discharge.
A theoretical and experimental study on the growth and properties of a ternary carbon-based material, CS x F y , synthesized from SF6 and C as primary precursors is reported. The synthetic growth concept was applied to model the possible species resulting from the fragmentation of SF6 molecules and the recombination of S-F fragments with atomic C. The possible species were further evaluated for their contribution to the film growth. Corresponding solid CS x F y thin films were deposited by reactive direct current magnetron sputtering from a C target in a mixed Ar/SF6 discharge with different SF6 partial pressures ([Formula: see text]). Properties of the films were determined by x-ray photoelectron spectroscopy, x-ray reflectivity, and nanoindentation. A reduced mass density in the CS x F y films is predicted due to incorporation of precursor species with a more pronounced steric effect, which also agrees with the low density values observed for the films. Increased [Formula: see text] leads to decreasing deposition rate and increasing density, as explained by enhanced fluorination and etching on the deposited surface by a larger concentration of F/F2 species during the growth, as supported by an increment of the F relative content in the films. Mechanical properties indicating superelasticity were obtained from the film with lowest F content, implying a fullerene-like structure in CS x F y compounds.


Skin diseases in Greek and immigrant children in Athens.
This study aimed to characterize the spectrum of skin diseases affecting children in Greece. We retrospectively studied data for 4071 children, aged 0-12 years, who were examined and diagnosed with dermatoses at the outpatient clinic of a university dermatological hospital between December 2005 and August 2007. To evaluate changes in disease patterns, these data were compared with data for a cohort of 12,700 children diagnosed with skin diseases at the same clinic two to three decades earlier (in 1977, 1980, and 1983). The most frequent disease was dermatitis/eczema (34.7%), with atopic dermatitis found in 20.7% of children, contact dermatitis in 6.9%, pityriasis alba in 2.1%, and seborrheic dermatitis in 1.8%. Infections (19.3%), nevi (5.6%), scabies (4.8%), and insect bites (4.3%) followed. More viral (12%) than bacterial (3.7%) and fungal (3.6%) infections were noted. Warts constituted 53.2% of viral infections. Immigrants had an increased risk for bacterial infections and scabies. Children diagnosed with skin diseases 24-30 years earlier were younger; exhibited lower prevalences of dermatitis/eczema (P = 0.01), viral infections (P < 0.001) and nevi (P < 0.001); higher prevalences of bacterial and fungal infections (P < 0.001) and insect bites (P < 0.01); and similar rates of scabies (P = 0.17). This study documents the high prevalence of atopic dermatitis in the region, the increasing incidence of viral infections and nevi, and the continuing problem of scabies, especially in immigrants.


An idiopathic case of macroglossia.
A case of successful reduction glossectomy for idiopathic macroglossia is presented. Macroglossia varies in its degree of severity. With pronounced macroglossia, respiratory and feeding difficulties may ensue. Persistent macroglossia leads to speech problems and anterior open bite. The cause of macroglossia must be clearly defined, and true macroglossia separated from pseudomacroglossia. There are many congenital and acquired causes of true macroglossia. By far, the most common cause of macroglossia is muscular hypertrophy. No similar case of idiopathic macroglossia is encountered in the literature. Corrective reduction glossectomy for this reason is scarcely described in the literature.


Association of BDNF gene polymorphism with bipolar disorders in Han Chinese population.
Recent data suggest that brain-derived neurotrophic factor (BDNF) plays an essential role in neuronal plasticity and etiology of bipolar disorders (BPD). However, results from different studies have been inconsistent. In present study, 342 patients who met DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) criteria for bipolar disorders type I (BPD-I) or type II (BPD-II) and 386 matched health controls were enrolled, and TaqMan(®) SNP Genotyping Assays (Applied Biosystems, Foster City, CA, USA) were applied to detect the functional polymorphism rs6265 (Val66Met) of BDNF gene. Treatment response to lithium and valproate was retrospectively determined. The association between Val66Met polymorphism and BPD, treatment response to mood stabilizers, was estimated. The genotype and allele distribution of Val66Met polymorphism between BPD patients and control subjects showed significant difference (genotype: χ(2) = 6.18, df = 2, P = 0.046; allele: χ(2) = 5.01, df = 1, P = 0.025) with Met allele as risk factor for disease susceptibility (OR = 0.79, 95%CI as 0.64-0.97). The post hoc analysis interestingly showed that Met allele had opposite effect on the treatment response for BPD-I and BPD-II separately. For BPD-I patients, the response score in Val/Val group was significantly lower than that in Met allele carriers (t = -2.27, df = 144, P = 0.025); for BPD-II patients, the response score in Val/Val group was significantly higher than that in Met allele carriers (t = 2.33, df = 26, P = 0.028). Although these results should be interpreted with caution because of the limited sample for Val/Val genotype in BPD-II patients (N = 5), these findings strengthen the hypothesis that BDNF pathway gets involved in the etiology and pharmacology of BPD and suggest the differences between BPD-I and BPD-II.


The effect of distension of the pulmonary vein-atrial junction on activity of left atrial receptors.
1. In anaesthetized dogs, the activity from left atrial receptors with vagal afferent fibres has been examined during distension of small balloons in the pulmonary veins or the application of pulsatile pressures to an isolated perfused pouch of the left atrium.2. Eleven fibres were found in nineteen dogs. The receptors discharging into these fibres were located, post mortem, to the atrial endocardium and reasons are given for believing that these fibres were myelinated and the receptors were B or Intermediate.3. Distension of small balloons induced significant increases in the discharge of action potentials from the receptors, the increases were similar to those after infusions of saline or dextran.4. In the perfused pouch the ;dynamic' thresholds for pulsatile pressure were high as were the mean and pulsatile pressures required to induce bursts of action potentials similar to those observed from atrial receptors in the atrium of normal size. Restoration of the atrium to its normal size resulted in ;dynamic' thresholds and responses to changes in pressure within the normal range. The changes could be explained assuming the Laplace relationship.5. This evidence supports the conclusion from previous investigations in which these techniques were used, that the increase in discharge in atrial receptors with myelinated vagal fibres could be the cause of the increase in heart rate and urine flow.


Gamma-band deficiency and abnormal thalamocortical activity in P/Q-type channel mutant mice.
Thalamocortical in vivo and in vitro function was studied in mice lacking P/Q-type calcium channels (Cav2.1), in which N-type calcium channels (Cav2.2) supported central synaptic transmission. Unexpectedly, in vitro patch recordings from thalamic neurons demonstrated no gamma-band subthreshold oscillation, and voltage-sensitive dye imaging demonstrated an absence of cortical gamma-band-dependent columnar activation involving cortical inhibitory interneuron activity. In vivo electroencephalogram recordings showed persistent absence status and a dramatic reduction of gamma-band activity. Pharmacological block of T-type calcium channels (Cav3), although not noticeably affecting normal control animals, left the knockout mice in a coma-like state. Hence, although N-type calcium channels can rescue P/Q-dependent synaptic transmission, P/Q calcium channels are essential in the generation of gamma-band activity and resultant cognitive function.


Ultrasonic strain versus coronary flow velocity pattern for predicting regional wall motion recovery after primary coronary intervention for acute myocardial infarction.
Strain Doppler echocardiography can detect regional myocardial dysfunction after acute myocardial infarction (AMI). The aim of this study was to assess the utility of strain in predicting regional wall motion recovery after AMI compared with the coronary flow velocity pattern. Thirty-three patients with anterior AMIs undergoing successful coronary intervention were included. Longitudinal myocardial strain and coronary flow velocity were measured <24 hours after coronary intervention. Regional wall motion was analyzed by the anterior wall motion score index (A-WMSI). End-systolic strain (r = 0.72, P < .0001), peak strain (r = 0.58, P < .005), and corrected time to peak strain (the time delay from end-systolic to peak strain divided by the RR interval) (r = 0.80, P < .0001) showed good correlations with A-WMSI at 4 weeks. Similarly, diastolic deceleration time was significantly correlated with A-WMSI at 4 weeks (r = 0.69, P < .0001). The diagnostic value in predicting wall motion recovery was compared using a receiver operating characteristic curve. The area under the curve of corrected time to peak strain tended to be larger than that of diastolic deceleration time (0.94 +/- 0.04 vs 0.86 +/- 0.06). Strain can predict left ventricular wall motion recovery in patients with AMIs after coronary intervention comparable with predictions using the coronary flow velocity pattern.


Evidence for a clorgyline-resistant monoamine metabolizing activity in the rat heart.
When benzylamine was used as substrate, a component of the total monoamine oxidase (MAO) activity in the rat heart was found to be resistant to inhibition by clorgyline. The proportion of the total activity represented by this component, decreased as the rat grew. It was also inhibited by both semicarbazide and isoniazid but not by potassium cyanide. Inhibitor studies with MAO in subcellular fractions showed that this component was more concentrated in the microsomal and soluble fractions. However, it could not be concluded that the activity was entirely a soluble enzyme. Determination of quasi-Michaelis constants ("Km") for total benzylamine oxidizing activity revealed a high ("Km" of approximately 10(-5)M) and low ("Km" of approximately 5 X 10(-4)M) affinity component. The high affinity component was inhibited by semicarbazide and the low affinity component by clorgyline. In the presence of 10(-3)M clorgyline, the high affinity component showed substrate inhibition at higher substrate concentrations. The possibility is discussed that the clorgyline-resistant activity is due to an amine-oxidizing activity distinct from mitochondrial MAO.


Both relative insulin resistance and defective islet beta-cell processing of proinsulin are responsible for transient hyperglycemia in extremely preterm infants.
Many extremely preterm infants develop hyperglycemia in the first week of life during continuous glucose infusion. The objective of this study was to determine whether defective insulin secretion or resistance to insulin was the primary factor involved in transient hyperglycemia of extremely preterm infants. A prospective comparative study was conducted in appropriate-for-gestational-age preterm infants <30 weeks of gestational age with the aim specifically to evaluate the serum levels of proinsulin, insulin, and C-peptide secreted during transient hyperglycemia by specific immunoassays. Three groups of infants were investigated hyperglycemic (n = 15) and normoglycemic preterm neonates (n = 12) and normal, term neonates (n = 21). In addition, the changes in beta-cell peptide levels were analyzed during and after intravenous insulin infusion in the hyperglycemic group. Data were analyzed using analysis of variance and analysis of variance for repeated measures. At inclusion, insulin and C-peptide levels did not differ in hyperglycemic subjects and in preterm controls. Proinsulin concentration was significantly higher in the hyperglycemic group (36.5 +/- 3.9 vs 23.2 +/- 0.9 pmol/L). Compared with term neonates, proinsulin and C-peptide levels were higher in normoglycemic preterm infants (23.2 +/- 0.9 vs 18.9 +/- 2.71 pmol/L and 1.67 +/- 0.3 vs 0.62 +/- 0.12 nmol/L, respectively). During and after insulin infusion in hyperglycemic neonates, plasma glucose concentration fell and proinsulin and C-peptide levels were lowered (18.4 +/- 7.6 and 20.7 +/- 4.5 pmol/L, respectively). These data suggest that 1) preterm neonates are sensitive to changes in plasma glucose concentration, but proinsulin processing to insulin is partially defective in hyperglycemic preterm neonates; 2) hyperglycemic neonates are relatively resistant to insulin because higher insulin levels are needed to achieve euglycemia in this group compared with normoglycemic neonates. These results also show that insulin infusion is beneficial in extremely preterm infants with transient hyperglycemia.


Comprehensive risk assessment and source identification of selected heavy metals (Cu, Cd, Pb, Zn, Hg, As) in tidal saltmarsh sediments of Shuangtai Estuary, China.
Heavy metals do not degrade and can remain in the environment for a long time. In this study, we analyzed the effects of Cu, Cd, Pb, Zn, Hg, and As, on environmental quality, pollutant enrichment, ecological hazard, and source identification of elements in sediments using data collected from samples taken from Shuangtai tidal wetland. The comprehensive pollution indices were used to assess environmental quality; fuzzy similarity analysis and geoaccumulation index were used to analyze pollution accumulation; correlation matrix, principal component analysis, and clustering analysis were used to analyze pollution source; environmental risk index and ecological risk index were used to assess ecological risk. The results showed that the environmental quality was either clean or almost clean. Pollutant enrichment analysis showed that the four sub-regions had similar pollution-causing metals to the background values of the soil element of the Liao River Plain, which were ranked according to their similarity. Source identification showed that all the elements were correlated. Ecological hazard analysis showed that the environmental risk index in the study area was less than zero, posing a low ecological risk. Ecological risk of the six elements was as follows: As > Cd > Hg > Cu > Pb > Zn.


Optimization and validation of a fluorogenic dipeptidyl peptidase 4 enzymatic assay in human plasma.
During the development of a specific dipeptidyl peptidase 4 (DPP4) inhibitor to treat type 2 diabetes, a fluorogenic kinetic analysis for DPP4 enzymatic activity using Gly-Pro-Aminomethylcoumarin (AMC) as a substrate was optimized and validated for recombinant DPP4 and human plasma samples. The sensitivity, calibration curve, detection range, accuracy, precision, recovery efficiency, Km constant, short/long-term stability, and stability after freezing-thawing cycles were analyzed. DPP4 enzymatic activity (mU/min) was measured as the initial velocity (Vo) of the enzymatic reaction over time. The sensitivity of the Vo value was 14,488 mU/min for recombinant DPP4 and 17,995 mU/min for human plasma samples. The dynamic ranges of the calibration curve were linear and reliable between 1.11 × 104-1.86 × 106 mU/min of the mean Vo value and in the DPP4 concentration range of 23.4-3,000 ng/mL. The assay's accuracy and precision met acceptance criteria for all samples. Plasma DPP4 was stable under various storage temperatures, even after three freeze-thaw cycles. Our optimized, validated bioanalytic method for measuring DPP4 activity in plasma samples was successfully employed to evaluate the effect of evogliptin (DA-1229) tartrate, which irreversibly and dose-dependently inhibits DPP4 enzymatic activity, without the dilution effect of human plasma samples and irrespective of the co-treated metformin.


Periventricular gradient of T1 tissue alterations in multiple sclerosis.
Pathology in multiple sclerosis is not homogenously distributed. Recently, it has been shown that structures adjacent to CSF are more severely affected. A gradient of brain tissue involvement was shown with more severe pathology in periventricular areas and in proximity to brain surfaces such as the subarachnoid spaces and ependyma, and hence termed the "surface-in" gradient. Here, we study whether (i) the surface-in gradient of periventricular tissue alteration measured by T1 relaxometry is already present in early multiple sclerosis patients, (ii) how it differs between early and progressive multiple sclerosis patients, and (iii) whether the gradient-derived metrics in normal-appearing white matter and lesions correlate better with physical disability than conventional MRI-based metrics. Forty-seven patients with early multiple sclerosis, 52 with progressive multiple sclerosis, and 92 healthy controls were included in the study. Isotropic 3D T1 relaxometry maps were obtained using the Magnetization-Prepared 2 Rapid Acquisition Gradient Echoes sequence at 3 T. After spatially normalizing the T1 maps into a study-specific common space, T1 inter-subject variability within the healthy cohort was modelled voxel-wise, yielding a normative T1 atlas. Individual comparisons of each multiple sclerosis patient against the atlas were performed by computing z-scores. Equidistant bands of voxels were defined around the ventricles in the supratentorial white matter; the z-scores in these bands were analysed and compared between the early and progressive multiple sclerosis cohorts. Correlations between both conventional and z-score-gradient-derived MRI metrics and the Expanded Disability Status Scale were assessed. Patients with early and progressive multiple sclerosis demonstrated a periventricular gradient of T1 relaxation time z-scores. In progressive multiple sclerosis, z-score-derived metrics reflecting the gradient of tissue abnormality in normal-appearing white matter were more strongly correlated with disability (maximal rho = 0.374) than the conventional lesion volume and count (maximal rho = 0.189 and 0.21 respectively). In early multiple sclerosis, the gradient of normal-appearing white matter volume with z-scores > 2 at baseline correlated with clinical disability assessed at two years follow-up. Our results suggest that the surface-in white matter gradient of tissue alteration is detectable with T1 relaxometry and is already present at clinical disease onset. The periventricular gradients correlate with clinical disability. The periventricular gradient in normal-appearing white matter may thus qualify as a promising biomarker for monitoring of disease activity from an early stage in all phenotypes of multiple sclerosis.


IgA nephropathy: clearance kinetics of IgA-containing immune complexes.
IgA nephropathy (IgAN) is associated predominantly IgA deposition in the affected glomeruli and has been shown to be the most common glomerular disorder among young people in the world. Although the exact pathogenic mechanism underlying IgAN remains largely unknown, circulating IgA-containing immune complexes (IgA ICs) is considered to play a major role in initiating the development and evolution of the renal disorder. In this review article, we discuss the fundamental mechanisms of clearance kinetics of IgA ICs and related issues, covering the following: (1) role of circulating IgA ICs in the pathogenesis of IgAN and (2) elimination of IgA ICs from the body, with emphasis of the role of the liver and Fc receptors in immune cells.


Cleavage of BNIP-2 and BNIP-XL by caspases.
BNIP-2 and BNIP-XL are BCH domain-containing proteins that are implicated in programmed cell death. It has been reported that overexpression of BNIP-2 in neuroblastoma cell lines resulted in massive cell death, whereas BNIP-XL was upregulated during NGF-depletion-induced apoptosis in neuroblastoma and was involved in the regulation of differentiation, survival, and aggressiveness of tumor cells. Despite their importance in apoptosis, our understanding of BNIP-2 containing proteins is limited. In this communication, we demonstrate that both BNIP-2 and BNIP-XL are cleaved by caspases during apoptosis. Significantly, the caspase cleavage sites on BNIP-2 are located on its N-terminal EF-hand motif, while that on BNIP-XL is located upstream of the C-terminal BCH domain. Our results suggest that the caspase-mediated cleavage of BNIP-2 and BNIP-XL could result in the release of the BCH domain or smaller fragments that are crucial for their proapoptotic activities.


Daily activity, thermoregulation and water loss in the tiger beetle Cicindela hybrida.
1. The tiger beetle Cicindela hybrida is a diurnal predator inhabiting open sandy areas. The activity pattern on a sunny day in May with a mean maximum surface temperature of 40°C is described (Fig. 2). The inactive period is spent in burrows in the sand and it is suggested that a threshold of 19°C releases the daily round of activity (Fig. 5). The animals appear on the sand between 7.00 and 10.00 and the number reaches a maximum at 34-42°C (surface temp.). The duration of the activity period is indirectly determined by the number of available prey which is maximal at 36°C and decreases both at higher and lower temperatures. Mean onset and termination of activity occur at about 28°C (surface temp.) when the expected capture rate is 3 per hour. In actograph experiments, onset was controlled by the illumination and occurred several hours before "dawn" (Fig. 9). 2. The preferred body temperature is at about 35°C and thermoregulatory behaviour patterns are used in order to approach this. At low ambient temperatures, body temperature is increased by sun-basking, while at high temperatures stilting is used to prevent it from increasing above 35°C. If the temperature becomes intolerably high, the animals dig into the sand (Figs. 8, 16). Measurements of body temperatures in the field show that tiger beetles have partial regulation (Fig. 10) and it is suggested that this is because the cost of thermoregulation is low, but prey is not abundant enough to allow a full exploitation of this, and predation (hunger) interferes with the thermoregulation. 3. An estimation of the daily water loss under field conditions is presented based on measurements of the water loss in the laboratory at different temperatures and relative humidities. These values are weighted by the times actually spent at different combinations in the field (Figs. 17, 19). The loss amounts to about 10% per day of initial body weight, and it is concluded that tiger beetles have not evolved any special adaptations with respect to this factor.


Odontoblast primary cilia: facts and hypotheses.
Odontoblasts, the cells responsible for the dentine formation, are organized as a single layer of highly polarized and differentiated post-mitotic cells along the interface between the dental pulp and the mineralized tubules. They lay down the physiological secondary dentine throughout the life of the teeth. Odontoblasts play a central role in the transportation of calcium to the dentine and they possibly mediate early stages of sensory processing in teeth. A primary cilium, 9+0 configuration, have been regularly identified in a supra nuclear location. Calbindin D28k has been detected at the base of the cilium membrane. The cilium structure was positive with detyrosinated alpha tubulin antibodies in vivo and in cultured human odontoblasts. Transcripts of tektin, a protein involved in ciliogenesis, were expressed in vitro. The putative role of the primary cilium constituting a critical link between external teeth stimuli and odontoblast responses is extensively discussed.


Profiling Protein Arginine Deiminase 4 (PAD4): a novel screen to identify PAD4 inhibitors.
Protein Arginine Deiminase 4 (PAD4) has emerged as a leading target for the development of a Rheumatoid Arthritis (RA) pharmaceutical. Herein, we describe the development of a novel screen for PAD4 inhibitors that is based on a PAD4-targeted Activity-Based Protein Profiling reagent, denoted Rhodamine-conjugated F-Amidine (RFA). This screen was validated by screening 10 Disease Modifying Anti-Rheumatic Drugs (DMARDs) and identified streptomycin, minocycline, and chlortetracycline as micromolar inhibitors of PAD4 activity.


The birth interval hypothesis-does it really indicate the end of the primipaternity hypothesis.
Recent Norwegian data suggest the presence of a causal relationship between prolonged birth intervals and the risk for preeclampsia in subsequent pregnancies. It has been proposed that the birth interval data explain the known association between a change in paternity and the risk for preeclampsia. In this review, the authors explore alternative explanations for the Norwegian findings, and as such argue that there is currently no reason to reject the primipaternity hypothesis.


Agmatine improves the behavioral and cognitive impairments associated with chronic gestational ethanol exposure in rats.
Chronic maternal ethanol exposure leads to poor intelligence, impaired cognition and array of neurological symptoms in offsprings and commonly referred as fetal alcohol spectrum disorder (FASD). Despite high prevalence and severity, the neurochemical basis of FASD remains largely unexplored. The present study evaluated the pharmacological effects of agmatine in cognitive deficits associated with FAS in rat's offsprings prenatally exposed to alcohol. Pregnant rats received ethanol in liquid modified diet during the entire gestational period of 21 days. Offsprings were treated with agmatine (20-80 mg/Kg, i.p.) during early postnatal days (PND: 21-35) and subsequently evaluated for anxiety in elevated plus maze (EPM), depression in forced swim test (FST) and learning and memory in Morris's water maze (MWM) during post adolescent phase. Hippocampal agmatine, BDNF, TNF-α and IL-6 levels were also analyzed in prenatally ethanol exposed pups. Offsprings prenatally exposed to ethanol demonstrated delayed righting reflex, reduced exploratory behavior along with anxiety, depression-like behavior and impaired memory. These behavioral abnormalities were correlated with a significant reduction in hippocampal agmatine and BDNF levels and elevation in TNF-α and IL-6 immunocontent. Chronic agmatine (40 and 80 mg/Kg, i.p.) administration for 15 days (PND: 21-35), improved entries and time spent in open arm of EPM, decreased immobility time in FST. It also reduced latency to reach the platform location; increased the number of entries, time spent in platform quadrant and also number of crossing over platform quadrant when subjected to MWM test in prenatally ethanol exposed offsprings. This study provides functional evidences for the therapeutic potential of agmatine in cognitive impairment and other neurological complications associated with FASD.


Selective influences of cross-modal spatial-cues on preattentive auditory processing: a whole-head magnetoencephalography study.
The processing streams of the various sensory modalities are known to interact within the central nervous system. These interactions differ depending on the level of stimulus representation and attention. The current study focused on cross-sensory influences on stimulus change detection during unattended auditory processing. We employed an oddball paradigm to assess cortical processing using whole-head magnetoencephalography (MEG) in 20 volunteers. While subjects performed distraction tasks of varying difficulties, auditory duration deviants were applied randomly to the left or the right ear preceded (200-400 ms) by oculomotor, static visual, or flow field co-stimulation at either side. Mismatch fields were recorded over both hemispheres. Changes in gaze direction and static visual stimuli elicited the most reliable enhancement of deviance detection at the same side (most prominent at the right auditory cortex). Under both conditions, the lateralized unattended and unpredictive pre-cues acted analogously to shifts in selective attention, but were not reduced by attentional load. Thus, the early cognitive representation of sounds seems to reflect automatic cross-modal interference. Preattentive multisensory integration may provide the neuronal basis for orienting reactions to objects in space and thus for voluntary control of selective attention.


Optimizing bacteriophage engineering through an accelerated evolution platform.
The emergence of antibiotic resistance has raised serious concerns within scientific and medical communities, and has underlined the importance of developing new antimicrobial agents to combat such infections. Bacteriophages, naturally occurring bacterial viruses, have long been characterized as promising antibiotic alternatives. Although bacteriophages hold great promise as medical tools, clinical applications have been limited by certain characteristics of phage biology, with structural fragility under the high temperatures and acidic environments of therapeutic applications significantly limiting therapeutic effectiveness. This study presents and evaluates the efficacy of a new accelerated evolution platform, chemically accelerated viral evolution (CAVE), which provides an effective and robust method for the rapid enhancement of desired bacteriophage characteristics. Here, our initial use of this methodology demonstrates its ability to confer significant improvements in phage thermal stability. Analysis of the mutation patterns that arise through CAVE iterations elucidates the manner in which specific genetic modifications bring forth desired changes in functionality, thereby providing a roadmap for bacteriophage engineering.


Earth caring.
This article explores the interrelationships of environment, nursing, and caring and challenges the readers, particularly in light of the ecology crisis, to examine the apparent anthropocentric emphasis of current human care and caring theory. The intent is to engage all nurses in thoughtful study and reflection and in fruitful, friendly dialogue.


Changes in Oxygenation and Serological Markers in Acute Exacerbation of Interstitial Lung Disease Treated with Polymyxin B Hemoperfusion.
Polymyxin B direct hemoperfusion (PMX-DHP) has been tried in acute exacerbation of interstitial lung disease (AE-ILD) patients and has shown clinical benefit. In this study, we tried to investigate the change in oxygenation and serologic markers after PMX-DHP treatment in AE-ILD patients in Korea. We reviewed the medical records of twenty-two patients who were admitted for AE-ILD and underwent PMX-DHP treatment. Changes in vital signs and laboratory findings before and after treatment were compared and factors related to 90-day mortality were analyzed using the Cox regression model. Of the 22 included patients, 11 (50%) patients were diagnosed with idiopathic pulmonary fibrosis. In AE-ILD patients treated with PMX-DHP, the 28-day mortality rate was 45.5% and the 90-day mortality rate was 72.7%. The P/F ratio before and after PMX-DHP treatment significantly improved in patients from baseline to 24 h (median (IQR), 116.3 (88.5-134.3) mmHg vs. 168.6 (115.5-226.8) mmHg, p = 0.001), and 48 h (116.3 (88.5-134.3) mmHg vs. 181.6 (108.9-232.0) mmHg, p = 0.003). Also, white blood cells (WBCs) and C-reactive protein (CRP) were decreased after PMX-DHP treatment. High acute physiology and chronic health evaluation II scores were associated with 90-day mortality. In patients with AE-ILD, PMX-DHP treatment was associated with an improved P/F ratio and lower WBC and CRP levels.


Advancement in analytical techniques for the extraction of grape and wine volatile compounds.
The grape and wine aroma is one of the most determining factors of quality, therefore the study of their volatile composition is a very important topic in vitiviniculture. The range of concentrations in which many of these compounds are found is quite low, in concentrations of ng/L; due to this, a sample preparation stage is necessary before doing the chromatographic analysis of the volatile compounds. In this review, the main analytical techniques used for the extraction of volatile compounds in grapes and wines are studied. The techniques presented are liquid-liquid extraction (LLE), solid phase extraction (SPE), solid phase microextraction (SPME), stir bar sorptive extraction (SBSE), and thin film solid phase microextraction (TF-SPME). For each of these techniques, a description was made, and the different characteristics were numbered, as well as their main advantages and disadvantages. Furthermore, from the second technique, a comparison is made with the previous techniques, explaining the reasons why new techniques have emerged. Throughout the review it is possible to see the different techniques that have been emerging in the past years as an improvement of the classical techniques.


A novel nonsense mutation in PPP2R5D is associated with neurodevelopmental disorders and shows incomplete penetrance in a Chinese pedigree.
PPP2R5D mutations are known to cause neurodevelopmental disorders in an autosomal-dominant manner. To date, the vast majority of the reported cases in the literature have been sporadic with de novo mutations. There are no data regarding PPP2R5D mutation penetrance. We aimed to unravel the underlying genetic defects in 3 generations of a family affected by intellectual disability, neurodevelopmental delay, and facial dysmorphology. We performed detailed clinical examinations and whole-exome sequencing in the family. We identified a novel mutation, c.1321 C>T (p.Arg441*), in PPP2R5D. The mutation cosegregated with affected family members I-2 and II-7 but not II-3, who bears the mutation but is phenotypically healthy. Our whole-exome sequencing also excluded the involvement of pathogenic mutations in other genes known to be related to neurodevelopmental disorders. The mutation was predicted to introduce a premature stop codon at position 441, thereby truncating the 162 amino acids at the C-terminus of the encoded protein. We report a familial transmitted PPP2R5D-related neurodevelopmental disorder as well as a novel nonsense pathogenic mutation and its incomplete penetrance. Our study expands the mutational and phenotypic spectra of PPP2R5D-related neurodevelopmental disorders, broadens our understanding of these disorders, and will thus be valuable for mutation-based pre- and postnatal screening and genetic diagnosis of neurodevelopmental disorders.


Impaired lumbar movement perception in association with postural stability and motor- and somatosensory-evoked potentials in lumbar spinal stenosis.
A descriptive study of the associations between different neurophysiologic findings in patients with lumbar spinal stenosis. To evaluate the ability to sense a change in lumbar position and the associations between lumbar movement perception, postural stability, and motor-evoked potentials and somatosensory-evoked potentials. Patients with low back pain have impaired postural control and impaired lumbar proprioception. Altered motor-evoked potentials and somatosensory-evoked potentials have been often observed in lumbar spinal stenosis. The study included 26 patients with clinically and radiologically diagnosed lumbar spinal stenosis. Their ability to sense lumbar rotation was assessed in a previously validated motorized trunk rotation unit in the seated position. The abilities to indicate the movement direction and the movement magnitude were used as indexes of the ability to sense the lumbar rotatory movement. The postural stability was measured with a vertical force platform. The motor-evoked potentials were elicited by transcranial and lumbar stimulation and recorded from anterior tibialis muscles. The somatosensory-evoked potentials were elicited by transcutaneous electrical stimulation of the tibial nerve at the ankle. Twenty patients (76.9%; P = 0.006) reported the wrong movement direction. Furthermore, the patients consistently localized the movement sensation in their shoulders instead of the lumbar region. The altered motor-evoked potentials and somatosensory-evoked potentials were observed in 11 and 16 patients, respectively. Abnormal motor-evoked potentials had inconsistent associations with impaired movement perception and postural stability and abnormal somatosensory-evoked potentials had no associations with other findings. Many patients with lumbar spinal stenosis have difficulties in sensing the lumbar rotational movement, which may indicate impaired proprioceptive abilities. Abnormal motor-evoked potentials and somatosensory-evoked potentials are also frequent in lumbar spinal stenosis but do not necessarily occur in the same patients as the abnormal ability to sense trunk movement. These new findings add to our understanding of the pathophysiology of lumbar spinal stenosis.


Synthesis and antibacterial evaluation of novel 4-alkyl substituted phenyl beta-aldehyde ketone derivatives.
A series of novel 4-alkylphenyl beta-aldehyde ketones and their derivatives were designed and synthesized on the basis of the chemical structures of Houttuynin and beta-lactam antibiotics. Antibacterial activities of these compounds were investigated. The results demonstrated that most of the compounds tested had moderate antibacterial activities against gram-positive pathogen Staphylococcus aureus (ATTC-25923) than Houttuynin, and gram-positive bacteria were more susceptible to the compounds than gram-negative bacteria. Compound 23 was found to be the most potent compound with MIC of 1.0 microg/mL against S. aureus. Particularly, compounds 16, 22 and 23 showed more active antibacterial activities against the clinically important pathogenic bacteria, methicillin-resistant S. aureus (MRSA) than Houttuynin and levofloxacin. The preliminary structure-activity relationship (SAR) analysis suggested that (1) the introduction of appropriate alkyl substituents into position 4 of phenyl ring enhanced antibacterial activities of these compounds, and isopropyl substituent might be more favorable; (2) the presence of ketone carbonyl moiety might play a vital role in determining significant antibacterial activities of these compounds.


A State-of-the-Art Scoping Review on SARS-CoV-2 in Sewage Focusing on the Potential of Wastewater Surveillance for the Monitoring of the COVID-19 Pandemic.
The outbreak of coronavirus infectious disease-2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has rapidly spread throughout the world. Several studies have shown that detecting SARS-CoV-2 in untreated wastewater can be a useful tool to identify new outbreaks, establish outbreak trends, and assess the prevalence of infections. On 06 May 2021, over a year into the pandemic, we conducted a scoping review aiming to summarize research data on SARS-CoV-2 in sewage. Papers dealing with raw sewage collected at wastewater treatment plants, sewer networks, septic tanks, and sludge treatment facilities were included in this review. We also reviewed studies on sewage collected in community settings such as private or municipal hospitals, healthcare facilities, nursing homes, dormitories, campuses, airports, aircraft, and cruise ships. The literature search was conducted using the electronic databases PubMed, EMBASE, and Web Science Core Collection. This comprehensive research yielded 1090 results, 66 of which met the inclusion criteria and are discussed in this review. Studies from 26 countries worldwide have investigated the occurrence of SARS-CoV-2 in sewage of different origin. The percentage of positive samples in sewage ranged from 11.6 to 100%, with viral concentrations ranging from ˂LOD to 4.6 × 108 genome copies/L. This review outlines the evidence currently available on wastewater surveillance: (i) as an early warning system capable of predicting COVID-19 outbreaks days or weeks before clinical cases; (ii) as a tool capable of establishing trends in current outbreaks; (iii) estimating the prevalence of infections; and (iv) studying SARS-CoV-2 genetic diversity. In conclusion, as a cost-effective, rapid, and reliable source of information on the spread of SARS-CoV-2 and its variants in the population, wastewater surveillance can enhance genomic and epidemiological surveillance with independent and complementary data to inform public health decision-making during the ongoing pandemic.


Inhibition of cell signaling by the combi-nitrosourea FD137 in the androgen independent DU145 prostate cancer cell line.
FD137, a nitrosourea appended to a quinazoline ring, was designed to simultaneously block epidermal growth factor receptor (EGFR)-mediated signaling and damage genomic DNA in refractory EGF-dependent prostate tumors. The mixed inhibition of cell signaling and DNA damage by FD137 were determined by Western blotting, RT-PCR, flow cytometry, sulforhodamine B (SRB), and comet assay. FD137 and its metabolite FD110 induced a dose-dependent increase in inhibition of EGF-stimulated EGFR autophosphorylation and this translated into blockade of c-fos gene expression in DU145 cells. FD137 induced significant levels of DNA damage and showed 150-fold greater anti-proliferative activity than BCNU, a classical nitrosourea. In contrast to BCNU, complete inhibition of EGF-induced cell transition to S-phase was observed at concentrations of FD137 as low as 3 microM. FD137 could not only damage DNA, but also significantly block downstream EGFR-mediated signaling. The superior activity of FD137 may be imputable to the combined effect of its mixed EGFR/DNA targeting properties. This novel strategy may well represent a new approach to target nitrosoureas to EGFR-overexpressing carcinomas of the prostate.


Non-vernalization requirement in Chinese kale caused by loss of BoFLC and low expressions of its paralogs.
We identified the loss of BoFLC gene as the cause of non-vernalization requirement in B. oleracea. Our developed codominant marker of BoFLC gene can be used for breeding program of B. oleracea crops. Many species of the Brassicaceae family, including some Brassica crops, require vernalization to avoid pre-winter flowering. Vernalization is an unfavorable trait for Chinese kale (Brassica oleracea var. chinensis Lei), a stem vegetable, and therefore it has been lost during its domestication/breeding process. To reveal the genetics of vernalization variation, we constructed an F2 population through crossing a Chinese kale (a non-vernalization crop) with a kale (a vernalization crop). Using bulked segregant analysis (BSA) and RNA-seq, we identified one major quantitative trait locus (QTL) controlling vernalization and fine-mapped it to a region spanning 80 kb. Synteny analysis and PCR-based sequencing results revealed that compared to that of the kale parent, the candidate region of the Chinese kale parent lost a 9,325-bp fragment containing FLC homolog (BoFLC). In addition to the BoFLC gene, there are four other FLC homologs in the genome of B. oleracea, including Bo3g005470, Bo3g024250, Bo9g173370, and Bo9g173400. The qPCR analysis showed that the BoFLC had the highest expression among the five members of the FLC family. Considering the low expression levels of the four paralogs of BoFLC, we speculate that its paralogs cannot compensate the function of the lost BoFLC, therefore the presence/absence (PA) polymorphism of BoFLC determines the vernalization variation. Based on the PA polymorphism of BoFLC, we designed a codominant marker for the vernalization trait, which can be used for breeding programs of B. oleracea crops.


Neuroprotective effects of metabotropic glutamate receptor ligands in a 6-hydroxydopamine rodent model of Parkinson's disease.
Increasing evidence implicates glutamate-mediated excitotoxicity as a contributory factor in dopaminergic cell death in the substantia nigra pars compacta (SNc) in Parkinson's disease (PD). Previous studies have suggested that metabotropic glutamate receptor (mGluR) ligands are neuroprotective against excitotoxicity in vitro. In the present study, the neurotoxin 6-hydroxydopamine (6-OHDA) produced a significant loss (61.2 +/- 8.9%; P < 0.01) of tyrosine hydroxylase-immunopositive (TH+) cells in both the SNc and striatal dopamine (58.02 +/- 1.27%; P < 0.05) in control male Sprague-Dawley rats. Both losses were significantly attenuated by sub-chronic (7 day) treatment with the Group I mGluR antagonists, 2-methyl-6(phenylethynyl)-pyridine (MPEP) or (S)-(+)-alpha-amino-4-carboxy-2-methylbenzeneacetic acid (LY367385); the Group II mGluR agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC); or the Group III mGluR agonist, L(+)-2-amino-4-phosphonobutyric acid (L-AP4). These data demonstrate a neuroprotective action of mGluR ligands in vivo against 6-OHDA toxicity that has important implications for the treatment of PD.


The role of IL-6 in TBI and PTSD, a potential therapeutic target?
This literature review focuses on the role of IL-6 in TBI or PTSD-induced neuroinflammation. While TBI and PTSD are widely prevalent, these diagnoses are particularly common amongst veterans. Given the role of IL-6 in neuroprotection acutely, compared to detrimental chronically, targeting this cytokine at specific time points may be beneficial in modulating neuroinflammation. Current treatments for TBI or PTSD are variably affective. By reviewing the role of IL-6 in these two diagnoses, future studies can focus on therapeutics to treat neuroinflammation and ultimately reduce the devastating impacts of neuroinflammation on cognition in PTSD and TBI.


Entrainment of oscillatory neural activity in the cat's lateral geniculate nucleus.
Oscillatory neural activity in the frequency range 7-12 Hz is observed in the lateral geniculate nucleus (LGN) of the lightly anesthetized cat. This paper describes a series of experiments in which the interactions between ongoing oscillatory potentials and periodic photic and electrical stimuli are analyzed using frequency domain techniques. The principal results of these experiments are consistent with a model of the neural system as an entrainable oscillator in which ongoing oscillations are suppressed by stimulation at nearby frequencies, but coexist with stimulus frequencies farther away. The physiological interpretation of these results may be closely tied to the role of the LGN as a "gating" mechanism between retina and cortex.


Terms of endearment: Bacteria meet graphene nanosurfaces.
Microbial multidrug resistance poses serious risks in returning the human species into the pre-antibiotic era if it remains unsolved. While conventional research approaches to combat infectious diseases have been inadequate, nanomaterials are a promising alternative for the development of sound antimicrobial countermeasures. Graphene, a two-dimensional ultra-thin nanomaterial, possesses excellent electronic and biocompatibility properties, which position it in the biotechnology forefront for diverse applications in biosensing, therapeutics, diagnostics, drug delivery and device development. Yet, several questions remain unanswered. For instance, the way these nanosurfaces interact with the microbial entities is poorly understood. The mechanistic elucidation of this interface seems critical to determine the feasibility of applications under development. Are graphene derivatives appropriate materials to design potent antimicrobial agents, vehicles or effective diagnostic microsensors? Has the partition of major microbial resistance phenotypic determinants been sufficiently investigated? Can toxicity become a limiting factor? Are we getting closer to clinical implementation? To facilitate research conducive to answer such questions, this review describes the features of the graphene-bacterial interaction. An overview on paradigms of graphene-microbial interactions is expected to shed light on the range of materials available, and identify possible applications, serving the ultimate goal to develop deeper understanding and collective conscience for the true capabilities of this nanomaterial platform.


Quantifying uncertainty in NMR T2 spectra using Monte Carlo inversion.
Relaxation and diffusion data are often analyzed using a Laplace inversion algorithm that incorporates regularization. Regularization is used because Laplace inversion with finite and noisy data is an ill-conditioned problem for which many solutions exist for a given data set. This paper reports a different approach. Instead of finding a "best" solution by some ad hoc criterion, we developed an efficient Monte Carlo algorithm that generates thousands of probable solutions from which the statistical properties of the solution can be analyzed. We find that although all of the individual solutions are spiky, the mean solution spectrum is smooth and similar to the regularized solution. From the Monte Carlo solutions we obtain probability distributions for quantities derived from the spectrum, such as porosity and bound fluid. This ability to characterize the uncertainty of such quantities is novel.


Structural characterization of mouse immunoglobulin allotypic determinants (allotopes) defined by monoclonal antibodies.
We have generated a new series of monoclonal antibodies recognizing allotypic determinants on mouse IgG1, IgG2a, and IgG2b. In this communication we describe their reactivity at the molecular level. A number of genetic specificities (as defined by reactivity with sera from inbred strains) were divided into subspecificities (allotopes) by these analyses. With the exception of one allotope located in the hinge region of Igh-1b, all other 23 allotopes examined were preserved upon reduction and alkylation of immunoglobulin antigens. To further analyze the role of immunoglobulin conformation in presenting the allotopes, we assayed their presence on mixed Igh-1a/Igh-4a heavy chain molecules. The Igh-1a determinants were maintained, but the Igh-4a determinants were lost. Taken together, our results indicate that genetic polymorphisms at the Igh loci generate an enormous antigenic complexity, much of which relies on tertiary and quaternary protein structure for expression.


Prediction of digestibility and energy concentration of winter pasture forage and herbage of low-input grassland--a comparison of methods.
Regarding the estimation of the energy concentration or digestibility of herb-dominated forage and plant samples from winter pastures, it could be expected that the estimation is only reliable when in vitro methods with rumen fluid as inoculum (= gas production techniques) are used. For the verification of this thesis based on logical reflections, an in vitro-method with rumen fluid added as inoculum, as well as chemical, and enzymatic methods were applied under consideration of existing estimating functions. As a possible reason for the observed divergence of the methods, effects of fungal infections or, respectively, secondary compounds in herbs are discussed. At the present state of knowledge, it is adequate to estimate the energy concentration in vitro by gas tests, as far as fattening types like suckler cows and beef cattle are concerned, maybe in contrast to the forage evaluation for dairy cows.


Concurrent validity of an automated algorithm for computing the center of pressure excursion index (CPEI).
Center of Pressure Excursion Index (CPEI), a parameter computed from the distribution of plantar pressures during stance phase of barefoot walking, has been used to assess dynamic foot function. The original custom program developed to calculate CPEI required the oversight of a user who could manually correct for certain exceptions to the computational rules. A new fully automatic program has been developed to calculate CPEI with an algorithm that accounts for these exceptions. The purpose of this paper is to compare resulting CPEI values computed by these two programs on plantar pressure data from both asymptomatic and pathologic subjects. If comparable, the new program offers significant benefits-reduced potential for variability due to rater discretion and faster CPEI calculation. CPEI values were calculated from barefoot plantar pressure distributions during comfortable paced walking on 61 healthy asymptomatic adults, 19 diabetic adults with moderate hallux valgus, and 13 adults with mild hallux valgus. Right foot data for each subject was analyzed with linear regression and a Bland-Altman plot. The automated algorithm yielded CPEI values that were linearly related to the original program (R2=0.99; P<0.001). Bland-Altman analysis demonstrated a difference of 0.55% between CPEI computation methods. Results of this analysis suggest that the new automated algorithm may be used to calculate CPEI on both healthy and pathologic feet.


Triggered pH/redox responsive release of doxorubicin from prepared highly stable graphene with thiol grafted Pluronic.
Strategy, to develop stable graphene and well control hydrophobic drug release from the prepared graphene, is reported to achieve a biomedical platform in drug delivery system. Reduced graphene oxide (rGO) has been prepared using quaternized 2-chloro-3',4'-dihydroxyacetophenone to poly(ethylene glycol)-g-poly(dimethylaminoethyl methacrylate) [PEG-g-PDMA, QC-PEG] following catechol chemistry which exhibited excellent dispersibility in water. Installation of thiol grafted Pluronic (Plu-SH) results formation of disulfide bonds surrounding rGO/QC-PEG matrix and further aids to achieve high DOX loading efficiency as well as trigged responsive controlled release behavior of DOX from the matrixes by redox responsive Plu-SH and pH sensitive. The rGO/QC-PEG with Plu-SH matrix showed significant stability under different physiological conditions. In vitro DOX release was conducted against different reductive environment and at different pH to figure out the release kinetics. Investigation from MTT assay assures more biocompatible behavior of rGO/QC-PEG/Plu-SH than prepared reduced graphene oxide. Effects of introducing Plu-SH was flashed when QDs loaded rGO/QC-PEG was applied to cell and examining the emitted fluorescence behavior from the cell by confocal images. The confocal investigation showed that high quenching effect of graphene is an obstacle to trace their position if it is used in cell tracking where application of Plu-SH could minimize this.


Socially Integrated Polysubstance (SIP) system: An open-source solution for continuous monitoring of polysubstance fluid intake in group housed mice.
Despite impressive results from neuroscience research using rodent models, there is a paucity of successful translation from preclinical findings to effective pharmacological interventions for treatment of substance use disorder (SUD) in humans. One potential reason for lack of translation from animal models is difficulty in accurately replicating the lived experience of people who use drugs. Aspects of substance use in humans that are often not modeled in animal research include but are not limited to 1) voluntary timing and frequency of substance intake, 2) social environment during substance use, and 3) access to multiple substances and multiple concentrations of each substance. Critically, existing commercial equipment that allows for social housing and voluntary polysubstance use (e.g., home cage monitoring system) is prohibitively expensive and no open-source solutions exist. With these goals in mind, here we detail development of the Socially Integrated Polysubstance (SIP) system, an open-source and lower cost solution that allows for group housed rodents to self-administer multiple substances with continuous monitoring and measurement. In our current setup, each SIP cage contains four drinking stations, and each station is equipped with a RFID sensor and sipper tube connected to a unique fluid reservoir. Using this system, we can track which animal (implanted with unique RFID transponder) visits which drinking location and the amount they drink during each visit (in 20 ul increments). Using four flavors of Kool-Aid, here we demonstrate that the SIP system is reliable and accurate with high temporal resolution for long term monitoring of substance intake and behavior tracking in a social environment. The SIP cage system is a first step towards designing an accessible and flexible rodent model of substance use that more closely resembles the experience of people who use drugs.


Hyperbaric oxygen therapy and coenzyme Q10 synergistically attenuates damage progression in spinal cord injury in a rat model.
Identifying effective spinal cord injury (SCI) treatments remains a major challenge, and current approaches are still unable to effectively improve its. Currently, we investigated the combined effects of hyperbaric oxygen (HBO) along with coenzyme Q10 (CoQ10) in the recovery of SCI in rats. Ninety female mature Sprague-Dawley rats were allocated into five equal groups, including; sham group, SCI group, HBO group (underwent SCI and received HBO), CoQ10 group (underwent SCI and received CoQ10), and HBO+CoQ10 group (underwent SCI and received HBO plus CoQ10). Tissue samples at the lesion site were obtained for evaluation of stereological, immunohistochemical, biochemical, molecular. Also, functional tests were performed to evaluate of behavioral properties. We found that a significant increase in stereological parameters, biochemical factors (GSH, SOD and CAT), IL-10 gene expression and behavioral functions (BBB and EMG Latency) in the treatment groups, especially HBO+CoQ10 group, compared to SCI group. In addition, MDA levels, the density of apoptotic cells, as well as expression of inflammatory genes (TNF-α and IL-1β) were considerably reduced in the treatment groups, especially HBO+CoQ10 group, compared to SCI group. We conclude that co-administration of HBO and HBO+CoQ10 has a synergistic neuroprotective effects in animals undergoing SCI.


Nanoscopy at low light intensities shows its potential.
A new form of green fluorescent protein allows super-resolution imaging to be performed faster on living cells with low radiation doses.


Finite element simulations of electrostatic dopant potentials in thin semiconductor specimens for electron holography.
Two-dimensional finite element simulations of electrostatic dopant potentials in parallel-sided semiconductor specimens that contain p-n junctions are used to assess the effect of the electrical state of the surface of a thin specimen on projected potentials measured using off-axis electron holography in the transmission electron microscope. For a specimen that is constrained to have an equipotential surface, the simulations show that the step in the projected potential across a p-n junction is always lower than would be predicted from the properties of the bulk device, but is relatively insensitive to the value of the surface state energy, especially for thicker specimens and higher dopant concentrations. The depletion width measured from the projected potential, however, has a complicated dependence on specimen thickness. The results of the simulations are of broader interest for understanding the influence of surfaces and interfaces on electrostatic potentials in nanoscale semiconductor devices.


Haemodialysis in rats.
A plate dialyser requiring an extracorporeal blood volume of 1.5 ml was developed to dialyse conscious rats. In experiments in vitro and in vivo its function was tested. The in vitro clearances of urea, creatinine and potassium were 126+/-9 ml/min/m2, 70.5+/-9 ml/min/m2, and 132.5+/-13 ml/min/m2, respectively. The method appears to be suitable for pharmacological and toxicological studies.


[New genus of monogeneans of the family Diplozoidae Palombi, 1949 (Monogenea)].
A study of the morphology of the species Diplozoon inustiatus Nag., 1965 has revealed distinct differences of this species from other members of Diplozoidae. On this bases Diplozoon inustiatus has been accorded a status of a distinct genus, Inustiatus. The diagnosis of this genus and a redescription of the species I. inustiatus are given.


Polybrominated diphenyl ethers and polychlorinated biphenyls in human breast adipose samples from Brazil.
Twenty five human breast adipose tissue samples were collected in Porto Alegre, Brazil during 2004-2005 and analyzed for polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs). SigmaPBDE concentrations (sum of tri- to hepta-BDEs) ranged from 0.19 to 132 ng/g lipid with a median of 1.51 ng/g lipid. These concentrations are 3- to 100-times lower than those reported from other countries, with the exception of Japan, probably reflecting lower usage of PBDE-containing products or lower exposures to these chemicals. The predominant congener was BDE-47, followed by BDEs 99, 183, 153 and 100. One individual in the dataset had about 70-times higher PBDE concentrations than the rest of the participants. SigmaPCB (sum of PCBs 118, 138, 153, 180) ranged from 30 to 339 ng/g lipid, with a median of 51 ng/g lipid. No age dependency was found for PBDEs (r=-0.800-0.374, p>0.05) or PCB 180 (r=0.278, p>0.05). On the other hand, PCBs 118, 138 and 153 did show age dependency (r=0.410-0.458, p<0.05). This is the first study to report levels of PBDEs in human breast adipose from Brazil.


Late-onset granular intra-amniotic infection following amniotic membrane transplantation.
The amniotic membrane (AM) is used in ocular surface reconstruction and is effective at promoting epithelialization and preventing corneal perforation in cases of acute microbial keratitis. Here, we report a case of isolated AM infection after AM transplantation for a persistent epithelial defect following tectonic penetrating keratoplasty. A 47-year-old man with poorly controlled type 2 diabetes mellitus presented to the emergency department with a referral for perforated microbial keratitis. After ophthalmic examination, corneal scraping was performed, and corneal gluing was attempted and failed. Hence, the patient underwent tectonic penetrating keratoplasty. After keratoplasty, the patient developed a persistent epithelial defect that required AM transplantation as an overlay. Thirty days post-AM transplant, the patient presented with signs and symptoms resembling granular microbial infection of the cornea. After two days, the granular findings began dislodging from the corneal surface and were sent for culture, sensitivity, and histopathological identification. Histological analysis of the granular material indicated it to be a small piece of AM stroma infiltrated with mixed-type inflammatory cells. Corneal scraping cultures indicated Streptococcus mitis and Streptococcus oralis. The infiltrate was localized to the basement membrane of the AM as, despite the anti-inflammatory effects of AM, it can also act as a barrier against polymorphonuclear leukocyte infiltration from the tear film and microbial invasion into the cornea.


Ectopic parvalbumin expression in mouse forebrain neurons increases excitotoxic injury provoked by ibotenic acid injection into the striatum.
A neuroprotective role for Ca(2+)-binding proteins in neurodegenerative conditions ranging from ischemia to Alzheimer's disease has been suggested in several studies. A key phenomenon in neurodegeneration is the Ca(2+)-mediated excitotoxicity brought about by the neurotransmitter glutamate. To evaluate the relative ability to resist excitotoxicity of neurons containing the slow-onset Ca(2+)-binding protein parvalbumin (PV), we injected the glutamate agonist ibotenic acid (IBO) into the striatum of adult mice ectopically expressing PV in neurons. Striatal ibotenic acid injection results in local nerve cell loss and reactive astrogliosis. Light microscopic evaluation, carried out after a delay of 2 and 4 weeks, reveals an enlarged and accelerated neurodegenerative process in mice ectopically expressing neuronal PV. Thus, PV is not neuroprotective, it rather enhances nerve cell death. This result implicates that the increase in cytosolic Ca(2+)-buffering capacity in the transgenic mice impairs other systems involved in Ca2+ sequestration. In addition, ultrastructural morphometric analysis shows that in neurons the mitochondrial volume is reduced in mice ectopically expressing neuronal PV. This is paralleled by a reduction in the amount of the mitochondrial marker enzyme cytochrome c oxidase subunit I (COXI). We conclude that alterations in the Ca(2+) homeostasis present in mice ectopically expressing neuronal PV are more deleterious under excitotoxic stress and largely outweigh the potential benefits of an increased Ca(2+)-buffering capacity resulting from PV.


Influence of electrostatic forces on particle propulsion in the evanescent field of silver ion-exchanged waveguides.
The effect of electrostatic interaction between carboxylate- and amino-functionalized polystyrene particles and a charged waveguide surface on the propulsion speed in optical tweezers is considered to be a function of the pH and ionic strength. It was shown that with the variation of the pH of the aqueous solution in which the particles were immersed, a systematic change in propulsion speed with a maximum speed could be achieved. The appearance of a maximum speed was ascribed to changes in the particle-waveguide separation as a result of the combination of two forces: Coulomb repulsion/attraction and induced dipole forces. The highest maximum speed at low ionic strength was around 12 μm/s. Changes in the ionic strength of the solution influenced the gradient of the dielectric constant near the involved surfaces and also led to a slightly reduced hydrodynamic radius of the particles. The combination of these effects subsequently increased the maximum speed to about 23 μm/s.


Pediatric liver transplantation: report on 52 patients with a 2-year survival of 86%.
Between March 1984 and March 1987, 59 orthotopic liver transplantations have been performed in 52 children at the Catholic University of Louvain in Brussels. The actuarial survival was 86% +/- 5 up to 3 years of evolution. The most frequent indication has been chronic hepatic insufficiency (43 patients) mainly because of biliary atresia; seven patients were transplanted for acute hepatic insufficiency and only two for liver tumor. Because of important donor/recipient weight discrepancy, a reduced-size liver was used in 20 occasions either for first or second transplant. No difference in the incidence of major complications were seen between whole liver and reduced size liver transplanted children, with the exception of more frequent subhepatic collections in the first and more hepatic artery thrombosis in the second group. Liver tests, clinical rehabilitation, and survival appear to be equal in the two groups.


Mammographic breast density as an intermediate phenotype for breast cancer.
The amount of radiologically dense breast-tissue appearing on a mammogram varies between women because of differences in the composition of breast tissue, and is referred to here as mammographic density. This review presents evidence that mammographic density is a strong risk factor for breast cancer, and that risk of breast cancer is four to five times greater in women with density in more than 75% of the breast than in women with little or no density in the breast. Density in more than 50% of the breast could account for about a third of breast cancers. The epidemiology of mammographic density is consistent with its being a marker of susceptibility to breast cancer. Twin studies have shown that the proportion of the breast occupied by density, at a given age, is highly heritable, and inherited factors explain 63% of the variance. Mammographic breast density has the characteristics of a quantitative trait and might be determined by genes that are easier to identify than those for breast cancer itself. The genes that determine breast density might also be associated with risk of breast cancer, and their identification is also likely to provide insights into the biology of the breast and identify potential targets for preventive strategies.


[Early detection of hearing loss. Example of intervention in public health].
We present a statistic study comparing all the options we can take to face congenital deafness as a problem of public health. We collected and analyzed data obtained between 1991 and 1995, just before our universal screening program started. They were separated into two groups with the 144 children explored using ABR, and the results were compared depending on the option taken in each group (no screening or high risk screening) and finally with those obtained in a universal program. The establishment of a high risk screening program was followed by a drastic reduction of the severe deafness diagnosis (29.5% to 8%), and also of the mean age of diagnosis (24 to 14 months), which were found statistically significant. The mean age with universal screening is 3 months. Early detection of congenital hearing impairment has brought an important advance in the management of this problem of public health minimizing its sequels as the diagnosis is reached earlier. The universal screening of deafness is feasible as based on cheap and easy diagnostic techniques available in any centre, and it must be performed with the rest of Health Children Programs.