Exploring Cascading Effects of Multimodal Communication Skills in Infants With Hearing Loss.
Infants and toddlers with hearing loss (HL) are at risk for developing communicative delays that can have a substantial lasting effect. Understanding child characteristics that may be targeted in early intervention is essential to maximizing communicative outcomes in children with HL. Among the most malleable predictors of communication skills include maternal responsivity, gestures, and vocalizations. The purpose of this study was to examine the relationship among maternal responsivity, prelinguistic communication skills and expressive vocabulary in children with HL. Based upon the results we propose a theoretical cascading model of communicative outcomes for children with HL such that gesture use may be associated with future vocalizations which may in turn be related to long-term spoken language outcomes. This exploratory model may be supported by the underlying transactional model of bidirectional language development that occurs through maternal sensitivity in the first two years of life. Additionally, parents of children with HL may be less likely to respond to a single mode of communication than to a combination of modes. This exploratory study provides a theoretical framework by which multimodal communication development in infants and toddlers with HL may be better understood, and suggests hypotheses for future research and implications for intervention practice.


Arabidopsis MSL10 has a regulated cell death signaling activity that is separable from its mechanosensitive ion channel activity.
Members of the MscS superfamily of mechanosensitive ion channels function as osmotic safety valves, releasing osmolytes under increased membrane tension. MscS homologs exhibit diverse topology and domain structure, and it has been proposed that the more complex members of the family might have novel regulatory mechanisms or molecular functions. Here, we present a study of MscS-Like (MSL)10 from Arabidopsis thaliana that supports these ideas. High-level expression of MSL10-GFP in Arabidopsis induced small stature, hydrogen peroxide accumulation, ectopic cell death, and reactive oxygen species- and cell death-associated gene expression. Phosphomimetic mutations in the MSL10 N-terminal domain prevented these phenotypes. The phosphorylation state of MSL10 also regulated its ability to induce cell death when transiently expressed in Nicotiana benthamiana leaves but did not affect subcellular localization, assembly, or channel behavior. Finally, the N-terminal domain of MSL10 was sufficient to induce cell death in tobacco, independent of phosphorylation state. We conclude that the plant-specific N-terminal domain of MSL10 is capable of inducing cell death, this activity is regulated by phosphorylation, and MSL10 has two separable activities-one as an ion channel and one as an inducer of cell death. These findings further our understanding of the evolution and significance of mechanosensitive ion channels.


Age and seasonal-dependent variations in the biochemical composition of boar semen.
This study investigated the effect of age- and seasonal-related variations in the composition of boar semen over a 3-year period. At the onset of 8 months of age, ejaculates were collected from four boars and allocated into three groups: 8 to 18, 19 to 30, and 31 to 42 months and were divided into two seasonal periods: autumn-winter and spring-summer. Boar variability had a significant effect on most of the analyzed semen parameters. Significantly, higher ejaculate volumes were observed in the boars older than 18 months of age during the autumn-winter period. Sperm concentration was higher in boars less than the age of 18 months of age, whereas the total sperm numbers were significantly higher during the autumn-winter period, regardless of the age group. Seasonal effects in sperm motility were more marked in boars at the age of 19 to 30 months, being significantly higher during the autumn-winter period. The proportions of spermatozoa with intact, normal apical ridge acrosome, and osmotically tolerant acrosomal membranes were markedly higher in boars at the age of 19 to 30 months during the autumn-winter period. Spermatozoa harvested during the spring-summer period were more susceptible to lipid peroxidation, irrespective of the age group. Significantly, higher levels of protein content and concentrations of nonthiol-containing antioxidant components of the seminal plasma (SP) were detected in boars less than 18 months of age during the autumn-winter period. Seasonal effects on the pH and proteinase inhibitory activity in the SP were more marked in boars less than 18 months of age, whereas alkaline phosphatase activity was greater in boars at the age of 19 to 30 months during the autumn-winter period. Substantial amounts of the thiol-containing antioxidants of the SP were detected in boars older than 18 months of age during the spring-summer period. Neither osmolality nor total antioxidant status was affected by differences in the seasonal periods or age groups. The findings of this study indicate that age- and seasonal-related variations affect the reproductive tract functions in the boar, resulting in marked changes in the biochemical composition of the semen.


Ganoderma Triterpenoids Exert Antiatherogenic Effects in Mice by Alleviating Disturbed Flow-Induced Oxidative Stress and Inflammation.
Ganoderma mushrooms, used in traditional Chinese medicine to promote health and longevity, have become widely accepted as herbal supplements. Ganoderma lucidum (GL), a commonly seen ganoderma species, is commercially cultivated under controlled conditions for more consistent chemical composition. The medicinal properties of GL are attributable to its antioxidant and anti-inflammatory activities. We intended to assess the effect of GL in atherosclerosis, an arterial condition associated with chronic oxidative stress and inflammation, using a carotid-artery-ligation mouse model. Flow turbulence created in the ligated artery induces oxidative stress and neointimal hyperplasia, a feature of early atherogenesis. Daily oral GL prevented neointimal thickening 2 weeks after ligation. Moreover, the ganoderma triterpenoid (GT) crude extract isolated from GL abolished ligation-induced neointima formation. Mechanistically, endothelial dysfunction was observed 3 days after ligation before any structural changes could be detected. GTs alleviated the oxidative stress and restored the atheroresistent status of endothelium by inhibiting the induction of a series of atherogenic factors, including endothelin-1, von Willebrand factor, and monocyte chemoattractant protein-1 after 3-day ligation. The anti-inflammatory activity of GTs was tested in cultured human umbilical vein endothelial cells (HUVECs) exposed to disturbed flow in an in vitro perfusion system. GTs abolished the induction of proinflammatory VCAM-1, TNF-α, and IL-6 by oscillatory shear stress. Moreover, the antioxidant activity of GTs was tested in HUVECs against the insult of H2O2. GTs dissipated the cellular superoxide accumulation imposed by H2O2, thereby mitigating H2O2-induced cell damage and proatherogenic response. Our results revealed the atheroprotective properties of ganoderma mushrooms and identified triterpenoids as the critical constituents for those effects. GTs prevent atherogenesis by eliminating disturbed flow-induced oxidative stress and inflammation.


HIV-related knowledge and AIDS stigma among college students in Yemen.
The present study analysed data from 501 Yemeni university students to examine their knowledge about HIV and their attitudes towards people with HIV/AIDS. The findings indicate that participants had several serious misunderstandings about HIV/AIDS and held negative attitudes toward people living with HIV/ AIDS. Although female students were less knowledgeable about HIV/AIDS than were male students, they held more positive attitudes toward people with HIV/AIDS. An overwhelming number of students expressed their willingness to get tested for HIV and recognized that AIDS is a serious issue facing their country. The study provides suggestions for HIV prevention efforts and ideas for future studies in Yemen.


The effect of ankle-foot orthoses on self-reported balance confidence in persons with chronic poststroke hemiplegia.
One intervention often used to address physical impairments post stroke is an ankle-foot orthosis. Ankle-foot orthoses may improve walking speed, stride length, and gait pattern. However, effects on balance, crucial for safe ambulation, are thus far inconclusive. One aspect of balance shown to contribute to functional ability is self-efficacy. Self-efficacy, defined as the belief in one's ability to succeed in particular situations, has been shown to be more strongly associated with activity and participation (as defined by the International Classification of Functioning, Disability, and Health) than physical performance measures of gait or balance. We investigated whether self-efficacy, or balance confidence when referred to in the context of balance capabilities, is improved with ankle-foot orthosis use. Repeated measures study design. Balance confidence was measured using the Activities-specific Balance Confidence Scale in 15 persons with chronic poststroke hemiplegia, with and without their regular ankle-foot orthosis. Activities-specific Balance Confidence Scale scores were significantly higher (p ≤ 0.01) for the ankle-foot orthosis condition compared to no ankle-foot orthosis. One mechanism by which ankle-foot orthosis use may influence balance is improved balance confidence. Future work should explore the specific mechanisms underlying this improvement in self-efficacy. Clinical relevance Self-efficacy may be an important factor to consider when evaluating functioning post stroke. Rehabilitative interventions that improve balance confidence may help restore participation and overall functioning in pathological populations, particularly in the fall-prone poststroke population. Study results provide evidence for improvements in balance confidence with ankle-foot orthosis use.


Association of Structural Magnetic Resonance Imaging Measures With Psychosis Onset in Individuals at Clinical High Risk for Developing Psychosis: An ENIGMA Working Group Mega-analysis.
The ENIGMA clinical high risk (CHR) for psychosis initiative, the largest pooled neuroimaging sample of individuals at CHR to date, aims to discover robust neurobiological markers of psychosis risk. To investigate baseline structural neuroimaging differences between individuals at CHR and healthy controls as well as between participants at CHR who later developed a psychotic disorder (CHR-PS+) and those who did not (CHR-PS-). In this case-control study, baseline T1-weighted magnetic resonance imaging (MRI) data were pooled from 31 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group. CHR status was assessed using the Comprehensive Assessment of At-Risk Mental States or Structured Interview for Prodromal Syndromes. MRI scans were processed using harmonized protocols and analyzed within a mega-analysis and meta-analysis framework from January to October 2020. Measures of regional cortical thickness (CT), surface area, and subcortical volumes were extracted from T1-weighted MRI scans. Independent variables were group (CHR group vs control group) and conversion status (CHR-PS+ group vs CHR-PS- group vs control group). Of the 3169 included participants, 1428 (45.1%) were female, and the mean (SD; range) age was 21.1 (4.9; 9.5-39.9) years. This study included 1792 individuals at CHR and 1377 healthy controls. Using longitudinal clinical information, 253 in the CHR-PS+ group, 1234 in the CHR-PS- group, and 305 at CHR without follow-up data were identified. Compared with healthy controls, individuals at CHR exhibited widespread lower CT measures (mean [range] Cohen d = -0.13 [-0.17 to -0.09]), but not surface area or subcortical volume. Lower CT measures in the fusiform, superior temporal, and paracentral regions were associated with psychosis conversion (mean Cohen d = -0.22; 95% CI, -0.35 to 0.10). Among healthy controls, compared with those in the CHR-PS+ group, age showed a stronger negative association with left fusiform CT measures (F = 9.8; P < .001; q < .001) and left paracentral CT measures (F = 5.9; P = .005; q = .02). Effect sizes representing lower CT associated with psychosis conversion resembled patterns of CT differences observed in ENIGMA studies of schizophrenia (ρ = 0.35; 95% CI, 0.12 to 0.55; P = .004) and individuals with 22q11.2 microdeletion syndrome and a psychotic disorder diagnosis (ρ = 0.43; 95% CI, 0.20 to 0.61; P = .001). This study provides evidence for widespread subtle, lower CT measures in individuals at CHR. The pattern of CT measure differences in those in the CHR-PS+ group was similar to those reported in other large-scale investigations of psychosis. Additionally, a subset of these regions displayed abnormal age associations. Widespread disruptions in CT coupled with abnormal age associations in those at CHR may point to disruptions in postnatal brain developmental processes.


Mitochondrial genome of the Neophocaena asiaeorientalis asiaeorientalis (Phocaenidae: Neophocaena).
Yangtze finless porpoise, Neophocaena asiaeorientalis asiaeorientalis, is a cetacea animal which has been reclassified as a Critically Endangered species by IUCN in 2013. In this study, we determined the complete mitochondrial genome of N. a. asiaeorientalis for use in future phylogenetic analyses. The complete mitochondrial genome of N. a. asiaeorientalis (16,385 bp in length) contained 37 genes (13 protein-coding genes, 2 rRNA genes, and 22 tRNA genes) and a non-coding region (D-loop). Additionally, a rep-origin (35 bp) exists which is located between tRNA(Asn) and tRNA(Cys).


Radiotherapy in India: History, current scenario and proposed solutions.
The history and current status of a biomedical discipline in a country or region provide important health system indicators. During the last one hundred years, radiotherapy has established its position as a vital specialty in cancer management. It has proved to be one of the most cost effective ways of treating cancer providing both radical and palliative treatments depending on patient stage and performance status. However, access to radiotherapy for cancer patients in India is limited by several factors including physical proximity of centre, cost and availability of required technology. This article gives an outline of the history, existing radiotherapy facilities and future trends related to radiotherapy practice in India.


Investigation of the AQP Family in Soybean and the Promoter Activity of TIP2;6 in Heat Stress and Hormone Responses.
Aquaporins (AQPs) are one diverse family of membrane channel proteins that play crucial regulatory roles in plant stress physiology. However, the heat stress responsiveness of AQP genes in soybean remains poorly understood. In this study, 75 non-redundant AQP encoding genes were identified in soybean. Multiple sequence alignments showed that all GmAQP proteins possessed the conserved regions, which contained 6 trans-membrane domains (TM1 to TM6). Different GmAQP members consisted of distinct Asn-Pro-Ala (NPA) motifs, aromatic/arginine (ar/R) selectivity filters and Froger's positions (FPs). Phylogenetic analyses distinguished five sub-families within these GmAQPs: 24 GmPIPs, 24 GmTIPs, 17 GmNIPs, 8 GmSIPs, and 2 GmXIPs. Promoter cis-acting elements analyses revealed that distinct number and composition of heat stress and hormone responsive elements existed in different promoter regions of GmAQPs. QRT-PCR assays demonstrated that 12 candidate GmAQPs with relatively extensive expression in various tissues or high expression levels in root or leaf exhibited different expression changes under heat stress and hormone cues (abscisic acid (ABA), l-aminocyclopropane-l-carboxylic acid (ACC), salicylic acid (SA) and methyl jasmonate (MeJA)). Furthermore, the promoter activity of one previously functionally unknown AQP gene-GmTIP2;6 was investigated in transgenic Arabidopsis plants. The beta-glucuronidase (GUS) activity driven by the promoter of GmTIP2;6 was strongly induced in the heat- and ACC-treated transgenic plants and tended to be accumulated in the hypocotyls, vascular bundles, and leaf trichomes. These results will contribute to uncovering the potential functions and molecular mechanisms of soybean GmAQPs in mediating heat stress and hormone signal responses.


Drug adherence and drug-related problems in pharmacotherapy for lower urinary tract symptoms related to benign prostatic hyperplasia.
Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) is one of the most common urinary disorders in elderly men. In recent years, pharmacotherapy of BPH has increased the efficacy, including combination treatment mostly with two drug classes, namely, 5-α-reductase inhibitors and α-1-adrenolytics (alpha blockers) with a different pharmacological activity. Although pharmacological treatment of BPH is a success story in urology, daily practice suggests that several medical needs remain unmet. We aimed to evaluate drug adherence in patients receiving pharmacological therapy to treat LUTS/BPH, and to analyze drug adherence among monotherapy and combination therapy. The sample population consisted of 758 men aged > 40 years who had been prescribed medications for LUTS/BPH during the index period between June 2015 and August 2016. Only alpha blockers and 5-α-reductase inhibitors (5ARIs) were considered in the analysis. Among ABs there were doxazosin, tamsulosin, alfuzosin, terazosin and among 5-α-reductase inhibitors it was only finasteride. Drug adherence was assessed in patients who were treated for a minimum of 6 months. Two levels of exposure were evaluated, follow-ups: ≥ 6 months, and ≥ 12 months. In patients who were treated for at least 6 months, the drug adherence rate was 32% and the 12-month drug adherence rate was 23%. We observed an inverse relationship between drug adherence rates and the duration of treatment - longer the duration of pharmacological therapy, lower was the drug adherence rate noted. Our study shows a low rate of overall drug adherence in patients diagnosed with BPH. It was observed that a low adherence rate is closely related to drug-related problems (DRP). Furthermore, this is a correlation between the degree of LUTS/BPH and adherence rate - the higher degree of LUTS/BPH, the higher adherence rate. Further studies are warranted focusing on assessing adherence to pharmacological therapy.


Interstitial cystitis in minority women.
A bladder disorder of unknown etiology, interstitial cystitis affects mainly women, and its prevalence may be increasing. Little information is available on the demographic, clinical, diagnostic, and treatment aspects of interstitial cystitis in the minority population. This retrospective review of the patient database at the Interstitial Cystitis Center, New England Medical Center, identified 17 minority women among a total of 201 patients who satisfied the criteria of the National Institutes of Health's National Institute of Diabetes and Digestive and Kidney Diseases for diagnosis of interstitial cystitis. Minority women accounted for 8.5% of the patients, with 3% being African American; 3.5%, Hispanic American; and 2.0%, Asian American. The clinical and endoscopic findings as well as responses to treatment were similar in both the minority and nonminority populations. However, the average duration of symptoms prior to diagnosis was 2.9 years in the minority group, compared with an average of 13 months in the nonminority group. Minority women with interstitial cystitis appear to be symptomatic for longer periods before a definitive diagnosis is made. Their response to treatment parallels that of the nonminority population. Further studies are needed to address the natural history, urologic referral patterns, and treatment outcomes in minority women who have interstitial cystitis.


Salivary gland tumours: immunoexpression of integrins beta 1, beta 3 and beta 4.
Integrins, heterodimeric transmembranic adhesion molecules composed of alpha and beta subunits, have been implicated in normal and neoplastic biological processes. We investigated the patterns of expression of integrins subunits beta 1, beta 3 and beta 4 in neoplasms derived from the terminal segment of salivary glands in order to understand their expression patterns in the different structures of these tumours. Immunohistochemistry using 'catalized signal amplification' (CSA) detection system was applied to paraffin-embedded specimens of polymorphous low-grade adenocarcinoma, adenoid cystic carcinoma and acinic cell carcinoma. Normal salivary glands were used as controls. Immunoexpression of integrins showed that neoplastic structures of the tumours studied tend to mimic the patterns seen in the normal structures of salivary glands from which they are derived. Anaplastic cells were negative for all integrins. This study revealed detailed topography of integrins in malignant tumours derived from intercalated acinar segment of salivary gland and this might be useful in the diagnosis of these lesions, especially of fine-needle aspiration (FNA) products or small specimens derived form incisional biopsies.


Biotemplated synthesis of metallic nanoparticle chains on an alpha-synuclein fiber scaffold.
Biomolecular templates provide an excellent potential tool for bottom-up device fabrication. Self-assembling alpha-synuclein protein fibrils, the formation of which has been linked to Parkinson's disease, have yet to be explored for potential device fabrication. In this paper, alpha-synuclein fibrils were used as a template for palladium (Pd), gold (Au) and copper (Cu) nanoparticle chains synthesis. Deposition over a range of conditions resulted in metal-coated fibers with reproducible average diameters between 50 and 200 nm. Active elemental palladium deposited on the protein fibrils is used as a catalyst for the electroless deposition of Au and Cu. Nanoparticle chains were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray energy dispersive spectrometry (XEDS), and electron energy loss spectrometry (EELS).


Comparison of general anesthesia with and without lumbar epidural for total hip arthroplasty: effects of epidural block on hip arthroplasty.
To determine whether lumbar epidural anesthesia, when combined with general anesthesia, decreases perioperative blood loss, the incidence of postoperative deep vein thrombosis (DVT), cardiac dysrhythmias, and ischemia in patients undergoing total hip arthroplasty (THA). Randomized, controlled study. A university hospital. 37 ASA physical status I, II, and III patients, undergoing elective THA. Patients were divided into two statistically comparable groups: Group GA = general anesthesia; Group CEGA = general anesthesia plus lumbar epidural anesthesia. All patients had 48-hour perioperative Holter monitoring, applied on admission, the day prior to surgery. In both groups, general anesthesia was induced with thiopental sodium and muscle relaxant, and maintained with oxygen, nitrous oxide, isoflurane, opioid, and muscle relaxant. Group B received lumbar epidural anesthesia with 10 ml 0.5% bupivacaine with 1:200,000 epinephrine prior to anesthesia induction. Blood loss was measured by suction bottle contents, sponge weights, and collection drainage. DVT was assessed with postoperative leg scanning, plethysmography, and venogram. Intraoperative blood loss was less after combined epidural-general anesthesia (663.8 ml +/- 299.0 ml) than after general anesthesia alone (1,259.2 ml +/- 366.0 ml). The difference was found to be statistically significant (p < 0.00005). No difference was found between the two groups in postoperative blood loss, incidence of DVT, cardiac dysrhythmias, or ischemia. Combined regional-general anesthesia decreases intraoperative blood loss in THA, and thereby offers an advantage over general anesthesia alone.


[Malacoplakia of the vagina. Cytological, histological and ultrastructural study of a case].
A case of vaginal malakoplakia is reported in a 65 year old patient receiving prednisone for fifteen months for the treatment of collagen colitis. The macroscopic and microscopic appearance, cytological examination of the vaginal smear and ultrastructural examination were typical of malakoplakia. To our knowledge, this is the seventh detailed case of vaginal malakoplakia and the twenty-sixth case of malakoplakia of the female genital tract.


Fine-scale spatial patterns in microbial community composition in an acid mine drainage.
Microbial community composition is essential for aquatic ecosystem functions and has been explored across diverse environments and various spatial scales. However, documented patterns are often based on samples from spatially/geographically separated locations or sites. Here, we define sampling volume as spatial scale and examine (by Illumina 16S rRNA sequencing) microbial community composition over a scale of 1 mL to 10 L in an acid mine drainage. β-Diversity analysis revealed that all samples grouped very tightly according to spatial scales and variations between every two scales were significant. Notably, mean β-diversity within each group was negatively correlated with spatial scales, indicating patchy microbial distribution. Partition of β-diversity further revealed that it was the relative abundances of some microbial taxa that largely changed among spatial scales. Phylogenetic analysis showed that microbial lineages were not randomly distributed, but displayed a tendency of more phylogenetically clustering at smaller spatial scales. Thus, we documented fine-scale spatial patterns in microbial community composition within a continuous aquatic environment, which may have practical implications for adequate sampling of aquatic systems in future studies.


Elucidating the intercalation of methylated 1,10-phenanthroline with DNA: the important weight of the CH/H interactions and the selectivity of CH/π and CH/n interactions.
Flat molecules like phenanthroline derivatives intercalate between base pairs of deoxyribonucleic acid and produce cytotoxic effects against tumoral cells. Elucidating the way of intercalation and its modulation on their efficiency by substitution still remains a challenging topic of research. In this work we analysed the intercalation via the major groove of methylated derivatives of phenanthroline, in different number and position, between guanine-cytosine base pairs. We studied our systems by using semi-empirical methods and density functional theory including dispersion corrections with the PM6-DH2 Hamiltonian and the B3LYP-D3 functional. We explored the geometry and electronic structure by means of the quantum theory of atoms in molecules and non-covalent interactions index analyses, whereas the interaction energy was estimated by means of two different approaches: one taking into account the results from the quantum theory of atoms in molecules analysis and the other based on the so-called energy decomposition analysis. The effect of solvation was also taken into consideration. Our studies show that CH/π and CH/n interactions by means of the -CH3 groups of methylated phen follow a clear pattern for any number of -CH3 groups and their position in the methylated phen ligand. That is, they try to produce the CH/π and CH/n interactions with the O and N heteroatoms of the base pairs and with the O atoms of the sugar and phosphate backbone. These findings suggest that the modulation of the intercalation of ligands that are able to form CH/π and CH/n weak interactions with the deoxyribonucleic acid is ruled not only by the number and position of the substitutions of the ligands but also by some key sites, which are the O and N atoms of the deoxyribonucleic acid in our analysed systems. It suggests some key and lock mechanism in which the interacting fragments fit like puzzle pieces in order to achieve the optimal interaction for the stabilization of the system. Interaction energies were calculated by using different approaches which converged to similar trends about the number and position of the -CH3 groups. The important weight of the CH/H interactions in the total interaction energy must be highlighted.


Improving Deproteinization in Colombian Latex from Hevea brasiliensis: A Bibliometric Approximation.
Natural Rubber Field Latex (NRFL) allergens restrict its use in some markets due to health-threatening allergic reactions. These molecules are proteins that are related to asymptomatic sensitization and hypersensitivity mediated by immunoglobulin E (IgE). Although NRFL allergens have been investigated since the 1980s, there are still gaps in knowledge regarding the development of deproteinized natural rubber (DPNR). Therefore, in this study, the deproteinization of NRFL from the lower basin of the Cauca River, Antioquia-Colombia was evaluated using eight systems. The highest removal value was 84.4% and was obtained from the treatment containing SDS (Sodium dodecyl sulfate), Urea, and Ethanol. It was also possible to determine that at high concentrations of SDS, removal percentages higher than 70% are reached. On the other hand, all deproteinizing systems decreased NRFL Zeta potentials without self-coagulation, suggesting enhanced colloidal stability in DPNR latex. On the other hand, the bibliometric analysis presented technological advances in DPRN through different parameters and bibliometric networks. The analysis presented makes an important contribution from the bibliometric approach that could be positive for the development of research on DPNR.


Increase of CD26/dipeptidyl peptidase IV expression on human gingival fibroblasts upon stimulation with cytokines and bacterial components.
CD26/dipeptidyl peptidase IV (DPPIV) is a cell surface ectoenzyme which participates in immune and inflammatory reactions. We found that CD26 was only partially expressed on human fibroblasts from periodontal tissues, whereas fibroblasts from lung and skin expressed CD26 constitutively as revealed by flow cytometry. We examined the possible upregulation of CD26 expression on human gingival fibroblasts in response to various stimulants. Interleukin-1alpha (IL-1alpha); tumor necrosis factor alpha; gamma interferon; lipopolysaccharide from Porphyromonas gingivalis, Prevotella intermedia, and Escherichia coli; and Prevotella glycoprotein augmented CD26 expression on gingival fibroblasts. Among the stimulants, IL-1alpha exhibited the most potent activity. Enzymatic activity of CD26 induced by IL-1alpha on fibroblasts was determined colorimetrically in terms of Gly-Pro hydrolysis of a synthetic chromogenic substrate, Gly-Pro p-nitroanilide. Among various inhibitors tested, diprotin A and phenylmethylsulfonyl fluoride inhibited the enzymatic activity, suggesting that the enzyme induced by IL-1alpha was DPPIV. The upregulation of CD26 mRNA expression upon stimulation with IL-1alpha was also revealed by a quantitative reverse transcription-PCR assay. In the kinetic experiment, 48 h and several days were required for maximum CD26 mRNA accumulation and CD26 molecule expression on the cell surface, respectively. The addition of cycloheximide at 2 h before IL-1alpha stimulation almost completely inhibited the accumulation of CD26 mRNA. These results suggested that induction of CD26 on human gingival fibroblasts is regulated at the transcriptional level and is also dependent on a de novo-synthesized protein factor(s).


Using wearable sensors to classify subject-specific running biomechanical gait patterns based on changes in environmental weather conditions.
Running-related overuse injuries can result from a combination of various intrinsic (e.g., gait biomechanics) and extrinsic (e.g., running surface) risk factors. However, it is unknown how changes in environmental weather conditions affect running gait biomechanical patterns since these data cannot be collected in a laboratory setting. Therefore, the purpose of this study was to develop a classification model based on subject-specific changes in biomechanical running patterns across two different environmental weather conditions using data obtained from wearable sensors in real-world environments. Running gait data were recorded during winter and spring sessions, with recorded average air temperatures of -10° C and +6° C, respectively. Classification was performed based on measurements of pelvic drop, ground contact time, braking, vertical oscillation of pelvis, pelvic rotation, and cadence obtained from 66,370 strides (~11,000/runner) from a group of recreational runners. A non-linear and ensemble machine learning algorithm, random forest (RF), was used to classify and compute a heuristic for determining the importance of each variable in the prediction model. To validate the developed subject-specific model, two cross-validation methods (one-against-another and partitioning datasets) were used to obtain experimental mean classification accuracies of 87.18% and 95.42%, respectively, indicating an excellent discriminatory ability of the RF-based model. Additionally, the ranked order of variable importance differed across the individual runners. The results from the RF-based machine-learning algorithm demonstrates that processing gait biomechanical signals from a single wearable sensor can successfully detect changes to an individual's running patterns based on data obtained in real-world environments.


Antepartum cardiotachometry for fetal evaluation.
Results of 686 nonstress tests with fetal monitoring were analyzed and compared to neonatal outcome. The use of an antepartum cardiotachometry screening (ACS) protocol seems to have reduced the perinatal mortality and morbidity in a high-risk group of patients to that of a low-risk group who did not undergo ACS.


Falls in Patients With Liver Cirrhosis.
Health-related quality of life (HRQOL) has become an important outcome for patients with liver cirrhosis as the number of transplantation candidates increases by the progression of treatment strategies. Falls and fall-related injuries are common in patients with liver cirrhosis and negatively affect HRQOL. Many factors increase the risk for falls such as minimal hepatic encephalopathy, psychoactive drugs, muscle strength, autonomic dysfunction, hyponatremia, and sleep problems. It is important to understand the underlying mechanisms for falls in cirrhotic patients to prevent severe injuries such as fractures, decrease healthcare costs, and improve HRQOL. Healthcare professionals, including physiotherapists and nurses, should be aware of the higher risk for falls in this population and therapeutic interventions must be designed for patients, especially those waiting on the transplant list.


Architectonic subdivision of the human orbital and medial prefrontal cortex.
The structure of the human orbital and medial prefrontal cortex (OMPFC) was investigated using five histological and immunohistochemical stains and was correlated with a previous analysis in macaque monkeys [Carmichael and Price (1994) J. Comp. Neurol. 346:366-402]. A cortical area was recognized if it was distinct with at least two stains and was found in similar locations in different brains. All of the areas recognized in the macaque OMPFC have counterparts in humans. Areas 11, 13, and 14 were subdivided into areas 11m, 11l, 13a, 13b, 13m, 13l, 14r, and 14c. Within area 10, the region corresponding to area 10m in monkeys was divided into 10m and 10r, and area 10o (orbital) was renamed area 10p (polar). Areas 47/12r, 47/12m, 47/12l, and 47/12s occupy the lateral orbital cortex, corresponding to monkey areas 12r, 12m, 12l, and 12o. The agranular insula (areas Iam, Iapm, Iai, and Ial) extends onto the caudal orbital surface and into the horizontal ramus of the lateral sulcus. The growth of the frontal pole in humans has pushed area 25 and area 32pl, which corresponds to the prelimbic area 32 in Brodmann's monkey brain map, caudal and ventral to the genu of the corpus callosum. Anterior cingulate areas 24a and 24b also extend ventral to the genu of the corpus callosum. Area 32ac, corresponding to the dorsal anterior cingulate area 32 in Brodmann's human brain map, is anterior and dorsal to the genu. The parallel organization of the OMPFC in monkeys and humans allows experimental data from monkeys to be applied to studies of the human cortex.


Preclinical Study of Dual-Wavelength Light-Emitting Diode Therapy in an Osteoarthritis Rat Model.
To evaluate the efficacy of light-emitting diode (LED) and their dual-wavelengths as a treatment strategy for osteoarthritis. We induced osteoarthritis in male Sprague-Dawley rats by intra-articular injection of sodium iodoacetate into the right rear knee joint. The animals with lesions were divided into an untreated group and an LED-treated group (n=7 each). In the LED-treated group, the lesioned knee was irradiated with lasers (850 and 940 nm) and dose (3.15 J/cm2) for 20 minutes per session, twice a week for 4 weeks. Knee joint tissues were stained and scanned using an in vivo micro-computed tomography (CT) scanner. Serum interleukin (IL)-6 and IL-18 levels were determined using enzyme-linked immuno-sorbent assay. Several functional tests (lines crossed, rotational movement, rearing, and latency to remain rotating rod) were performed 24 hours before LED treatment and at 7, 14, 21, and 28 days after treatment. LED-treated rats showed improved locomotor function and suppressed matrix-degrading cytokines. Micro-CT images indicated that LED therapy had a preserving effect on cartilage and cortical bone. LED treatment using wavelengths of 850 and 940 nm resulted in significant functional, anatomical, and histologic improvements without adverse events in a rat model. Further research is required to determine the optimal wavelength, duration, and combination method, which will maximize treatment effectiveness.


Developmental toxicity and neurobehavioral effects of sodium selenite and selenium nanoparticles on zebrafish embryos.
Selenium, a trace mineral, is essential for several physiological processes in humans and animals. It is an antioxidant vital for the immunological response, DNA synthesis, thyroid hormone metabolism, and antioxidant defense enzymes. Zebrafish embryos and larvae were exposed to different concentrations of sodium selenite (SodSe) and selenium nanoparticles (SeNs) at various developmental stages. The study evaluated the impact of SodSe and SeNs on larvae survival, hatching rate, and morphological abnormalities. Also, acridine orange staining was used to analyze the apoptotic cell death, and behavioral tests were conducted to assess anxiety-like behaviors. The results showed that both SodSe and SeNs influence the development and neurobehavior of zebrafish larvae in a concentration-dependent manner. SodSe at high concentration causes low survival rates, delayed hatching, and increased morphological defects in zebrafish larvae. In addition, exposure to SodSe resulted in elevated apoptosis in different larval tissues. Zebrafish larvae treated with SodSe and SeNs exhibited anxiety-like behaviour, increased thigmotaxis, less exploratory behaviour, and less swimming patterns. The nerve conductions and stimuli responses evaluated through acetylcholine esterase (AChE) and cortisol assays, revealed a decrease in the activity in a dose-dependent manner of SodSe and SeNs. Interestingly, the effects of SeNs were lower even at higher concentrations when compared with SodSe at lower concentrations on zebrafish embryos. This shows that SeNs synthesized through biological methods may be less toxic and may have lower effect on the development and neurobehavior of zebrafish larvae. Thus, our study confirms the cytotoxic and neurobehavioral effects of SodSe and suggests the use of SeNs at lower concentration to provide insights into better understanding of developmental stages and metabolic pathways in zebrafish larvae.


The very model of a modern etiology: a biopsychosocial view of peptic ulcer.
Research on ulcer psychosomatics has plummeted since the early 1970s, to the applause of many who argue that ulcer is simply an infectious disease. The purpose of this article is to discuss the relevance of ulcer psychogenesis in the age of Helicobacter pylori. A critical literature review was conducted. There is a substantial and methodologically sound body of prospective studies linking stress with the onset and course of peptic ulcer. Psychosocial factors can be estimated to contribute to 30% to 65% of ulcers, whether related to nonsteroidal antiinflammatory drugs, H. pylori, or neither. The observed association between stress and ulcer is accounted for, in part, by recall bias, misreported diagnoses, and confounding by low socioeconomic status (a source of stress and of ulcer risk factors, such as H. pylori and on-the-job exertion) and by distressing medical conditions (which lead to use of nonsteroidal antiinflammatory drugs). Of the residual, true association, a substantial proportion is accounted for by mediation by health risk behaviors, such as smoking, sleeplessness, irregular meals, heavy drinking, and, again, nonsteroidal antiinflammatory drugs. The remainder results from psychophysiologic mechanisms that probably include increased duodenal acid load, the effects of hypothalamic-pituitary-adrenal axis activation on healing, altered blood flow, and impairment of gastroduodenal mucosal defenses. Peptic ulcer is a valuable model for understanding the interactions among psychosocial, socioeconomic, behavioral, and infectious factors in causing disease. The discovery of H. pylori may serve, paradoxically, as a stimulus to researchers for whom the concepts of psychology and infection are not necessarily a contradiction in terms.


Thiazole Containing Heterocycles with Antimalarial Activity.
Heterocyclic compounds are the main class of medicinally important compounds. Many heterocyclic compounds bearing a five-membered ring in their structure have a good spectrum of biological activities. Thiazole is an important class of five-membered heterocyclic compounds. Thiazole and its derivatives exhibited a broad range of biological activities due to the presence of various reaction posseses. Thiazole, heterocyclic nucleus is present in several potent pharmacologically active molecules such as Sulfathiazole (antimicrobial drug), Ritonavir (antiretroviral drug), Tiazofurin (antineoplastic drug) and Abafungin (antifungal drug) etc. The search for some novel biologically active thiazoles is to be continued in the field of medicinal chemistry for investigators. An aim of this review is to identify and try making a SAR (Structure Activity Relationship) of substituted thiazole nucleus as possible new antimalarials. Author undertook a structured search of bibliographic databases for peerreviewed research literature using a focused review question and inclusion/exclusion criteria. The quality of retrieved papers was appraised using standard tools. The characteristics of screened papers were described, and a deductive qualitative content analysis methodology was applied to analyse the interventions and findings of included studies using a conceptual framework. Fifteen papers were included in the review; the majority were described about many biological activity of thiazole nucleus. Seven papers were find that had impacted upon the thaizoles as antimalarials. Some papers focused on the design, synthesis and antimalarial activity evaluation of thiazole derivatives. This review identified and made a SAR (Structure Activity Relationship) of substituted thiazole nucleus as possible new antimalarials. This review describes ongoing research in the search for novel thiazoles as targets and new antimalarial drug molecules.


Using Deep Learning Artificial Intelligence Algorithms to Verify N-Nitroso-N-Methylurea and Urethane Positive Control Proliferative Changes in Tg-RasH2 Mouse Carcinogenicity Studies.
In Tg-rasH2 carcinogenicity mouse models, a positive control group is treated with a carcinogen such as urethane or N-nitroso-N-methylurea to test study validity based on the presence of the expected proliferative lesions in the transgenic mice. We hypothesized that artificial intelligence-based deep learning (DL) could provide decision support for the toxicologic pathologist by screening for the proliferative changes, verifying the expected pattern for the positive control groups. Whole slide images (WSIs) of the lungs, thymus, and stomach from positive control groups were used for supervised training of a convolutional neural network (CNN). A single pathologist annotated WSIs of normal and abnormal tissue regions for training the CNN-based supervised classifier using INHAND criteria. The algorithm was evaluated using a subset of tissue regions that were not used for training and then additional tissues were evaluated blindly by 2 independent pathologists. A binary output (proliferative classes present or not) from the pathologists was compared to that of the CNN classifier. The CNN model grouped proliferative lesion positive and negative animals at high concordance with the pathologists. This process simulated a workflow for review of these studies, whereby a DL algorithm could provide decision support for the pathologists in a nonclinical study.


Fluctuations of estradiol during women's menstrual cycle: Influences on reactivity towards erotic stimuli in the late positive potential.
While several studies examined the reactivity towards negative emotional stimuli across women's menstrual cycle, only few investigated responses to positive emotional cues in association with sexual hormones on a neural level. Therefore, the aim of the current EEG-experiment was to study the differential reactivity towards positive (erotic) words during the menstrual cycle (i.e. with fluctuations in the steroids estradiol and progesterone) in the late positive potential (LPP). Regarding reactivity towards erotic stimuli, the LPP is seen as the most relevant ERP-component, as more positive amplitudes in the LPP reflect larger incentive salience and higher arousal. The LPP towards erotic words was expected to be more pronounced during fertile phases of the menstrual cycle (around ovulation). Furthermore, associations with hormonal concentrations of estradiol and progesterone were investigated. 19 young, free cycling women were tested in an Erotic Stroop paradigm during the follicular phase, ovulation, and the luteal phase in a balanced cross-over design, while electroencephalogram (EEG) was recorded. LPPs in reaction to erotic compared to neutral words were larger in every phase. During the follicular phase and ovulation, higher estradiol-concentrations were associated with more positive LPP-amplitudes towards erotic- than to neutral words. No effects of progesterone, as well as no effects of cycle phase, were evident. Results are being discussed regarding implications for further research.


Ca-activated K channels in apical membrane of mammalian CCT, and their role in K secretion.
High conductance, Ca-activated K channels were studied in the apical membrane of the rat cortical collecting tubule (CCT) using the patch-clamp technique. In cell-attached patches the channels were found mainly in the closed state at the spontaneous apical membrane potential. They spent progressively more time in the open state as the pipette potential was made negative relative to the bath. In excised patches these channels had a high selectivity for K over Na and were activated by micromolar concentrations of Ca2+ on the cytoplasmic side of the membrane in a voltage-dependent manner. They had a low conductance to Rb and were blocked by Ba (1-100 microM) from the cytoplasmic side and tetraethylammonium (TEA) (0.2-1 mM) from the luminal side. Block by external TEA and small conductance to Rb were used to investigate the role of these channels in K transport by the isolated perfused rabbit CCT. Ba (2.5 mM), a well-studied blocker of apical K conductance in this segment, hyperpolarized the transepithelial voltage (VT) by 3.7 +/- 0.9 mV when added to the luminal solution of the perfused tubule. Addition of TEA (5 mM) to the luminal solution has no effect on VT. When Na transport was abolished by luminal amiloride, perfusion with 30 mM K (replacing Na) resulted in a lumen-negative VT (18-34 mV). Under these conditions, VT was reduced by 6.0 +/- 1.5 mV by 2.5 mM Ba, whereas TEA had no effect. Perfusion with 30 mM Rb (replacing Na) also caused a lumen-negative VT that was approximately 50% of that observed with 30 mM K. The apical K conductance of the perfused CCT appears to be insensitive to luminal TEA and only modestly selective for K over Rb. This conductance, at least under the conditions of our studies, is probably not mediated by the high conductance Ca-activated K channel.


Prehospital management of traumatic brain injury.
The aim of this study was to review the current protocols of prehospital practice and their impact on outcome in the management of traumatic brain injury. A literature review of the National Library of Medicine encompassing the years 1980 to May 2008 was performed. The primary impact of a head injury sets in motion a cascade of secondary events that can worsen neurological injury and outcome. The goals of care during prehospital triage, stabilization, and transport are to recognize life-threatening raised intracranial pressure and to circumvent cerebral herniation. In that process, prevention of secondary injury and secondary insults is a major determinant of both short- and longterm outcome. Management of brain oxygenation, blood pressure, cerebral perfusion pressure, and raised intracranial pressure in the prehospital setting are discussed. Patient outcomes are dependent upon an organized trauma response system. Dispatch and transport timing, field stabilization, modes of transport, and destination levels of care are addressed. In addition, special considerations for mass casualty and disaster planning are outlined and recommendations are made regarding early response efforts and the ethical impact of aggressive prehospital resuscitation. The most sophisticated of emergency, operative, or intensive care units cannot reverse damage that has been set in motion by suboptimal protocols of triage and resuscitation, either at the injury scene or en route to the hospital. The quality of prehospital care is a major determinant of long-term outcome for patients with traumatic brain injury.


Reducing Radiation Dose for High-resolution Flat-panel CT Imaging of Superior Semicircular Canal Dehiscence.
High-resolution flat panel computed tomography (FPCT) is useful for the evaluation of temporal bone pathologies. While radiation exposure remains a concern, efforts have been devoted to reduce dose, while maintaining image quality. We hypothesize that removing the antiscatter grid (ASG) results in decreased radiation exposure, while maintaining diagnostic image quality for the evaluation of superior semicircular canal dehiscence (SSCD). Ten patients with clinical suspicion for SSCD participated in this prospective study. Two sequential collimated 20-second FPCT acquisitions were performed (first: grid in; second: grid removed) in all patients. Secondary reconstructions were created by manually generating the volume of interest to include the middle ear using a voxel size of 0.1 mm and 512 × 512 matrix. Radiation dose parameters (air kerma (Ka,r) in mGy and dose area product (DAP) in μGym) were recorded. Three reviewers analyzed images for the ability to diagnose SSCD, to identify the stapes crurae, and to determine if an ASG was present. The average Ka,r and DAP for the grid-in acquisitions were 246.7 mGy (SD 47.9) and 2838.0 μGym (SD 862.8), versus 160.2 mGy (SD 33.2) and 2026.3 μGym (SD 644.8) for the grid-out acquisitions, respectively (p<0.001 for both Ka,r and DAP). Radiation exposure was reduced by approximately 30% solely by removing the ASG. All reviewers correctly identified all patients with SSCD (confirmed at surgery), with mean AUC of 0.99 (κ = 0.90). Removing the antiscatter grid during FPCT imaging of the temporal bones is a simple and effective way to reduce radiation exposure while maintaining diagnostic image quality for the evaluation of SSCD.


Layer- and cell-type-specific suprathreshold stimulus representation in rat primary somatosensory cortex.
Sensory stimuli are encoded differently across cortical layers and it is unknown how response characteristics relate to the morphological identity of responding cells. We therefore juxtasomally recorded action potential (AP) patterns from excitatory cells in layer (L) 2/3, L4, L5 and L6 of rat barrel cortex in response to a standard stimulus (e.g. repeated deflection of single whiskers in the caudal direction). Subsequent single-cell filling with biocytin allowed for post hoc identification of recorded cells. We report three major conclusions. First, sensory-evoked responses were layer- and cell-type-specific but always < 1 AP per stimulus, indicating low AP rates for the entire cortical column. Second, response latencies from L4, L5B and L6 were comparable and thus a whisker deflection is initially represented simultaneously in these layers. Finally, L5 thick-tufted cells dominated the cortical AP output following sensory stimulation, suggesting that these cells could direct sensory guided behaviours.


Stewart-Treves Syndrome on the Lower Extremity Associated to Idiopathic Chronic Lymphedema Visualized on FDG PET/CT.
Angiosarcomas are highly malignant and rare tumors of vascular or lymphatic endothelial cell origin with a poor prognosis. Lymphangiosarcoma associated with chronic lymphedema is known as Stewart-Treves syndrome. Stewart-Treves syndrome is primarily described in patients with lymphedema of an upper extremity occurring after breast cancer surgery including radical axillary lymph node dissection and subsequent radiotherapy. It is rarely described in the presence of idiopathic chronic lymphedema of the lower extremities. We present a case of lymphangiosarcoma visualized on F-FDG PET/CT, where Stewart-Treves syndrome is secondary to probably a combination of idiopathic chronic lymphedema of the lower extremities and systemic immunosuppressive treatment.


[The clinical outcome after occipitocervical fusion due to metastases of the upper cervical spine: a consecutive case series and a systematic review of the literature].
Increasing incidences of osseous metastatic malignancies and higher life expectancy in patients are resulting in a raise of occipitocervical metastases. Those patients with infaust prognosis have a significantly reduced quality of life. In Germany, between 800 and 1680 new cases per year are expected. Treatment algorithms include the evaluation of the general condition, the operability of visceral metastases, the tumor localization, the sensitivity to chemo-/radiotherapy, the fracture risk and the extent of neurological deficits and myelopathies. A systematic review on clinical studies or case series in posterior occipitocervical fusions due to metastases to the craniocervical transition yielded nine publications with 48 patients without neurological deficit. The mean survival time in the given follow-up was 6.44 months (n = 26; SD: 5,28; 95 % CI: 4.3-8.57). When measured, the clinical outcome was improved towards the VAS, the DENIS Pain Scale and the quality of life through the activities of daily living (ADL). We searched our clinical database for occipitocervical stabilizations in patients with craniocervical metastases. The prospectively collected data included the preoperative Tokuhashi score, SIN score, neurological status, length of hospitalization, perioperative course/loss of blood/complication rate, as well as the Karnofsky- index and pain measured by VAS preoperatively and in follow-up. Six patients were treated in this consecutive case series. The median age was 72 years (min./max.: 65/82), the average BMI 31.75 (min./max.: 19.3/38.1). The mean preoperative Karnofsky-index was 35 % (min./max.: 23.99/46.01; 95 % CI: 8.39) the mean preoperative Tokuhashi-score 7 (min./max.: 4/10), the mean preoperative VAS7 (min./max.: 4.8/9.2; 95 % CI: 1.68). There were no perioperative complications. In the follow-up, one patient showed a loosening of the screws in the osteolytic massae laterales and one patient suffered from a construct failure after fall. Metastases of the craniocervical transition are rare. The initial treatment of instability includes the application of a rigid Miami-J-collar or a Halo fixator. The decision for an operative procedure must accurately assess the individual patient characteristics to provide him a balanced concept between operational risk and clinical benefit. The assessment should be based on the life expectation and the expected quality of life in dependency of the respective therapeutic concept and its risks. The sole posterior stabilization of craniocervical instability through occipitocervical fusion leads to a reduction of pain, has a low perioperative risk, and may prevent a hospitalization. It is justified for selected patients to receive this treatment to help alleviate pain and to improve their quality of life. From our experience, rare cases of pain without instability should undergo conservative treatment in the first line. Due to the low availability of data on the manifestation and the clinical course of craniocervical metastases, there is a need for the collection of both the descriptive patient data include the radiographic findings as well as the clinical outcome and socio-economic factors using appropriate scoring systems.


Epigenetic modifications in hepatic stellate cells contribute to liver fibrosis.
Liver fibrosis represents the final common pathway of virtually all types of chronic liver diseases, and it has been a major public health concern. Many genes have been demonstrated to be involved in the pathogenesis of liver fibrosis, while the mechanisms underlying gene regulation still needs further research. On the other hand, hepatic stellate cells (HSCs) are quiescent cells in the perisinusoidal space in liver. HSCs facilitate hepatocytes interactions via releasing soluble inflammatory factors and producing extracellular matrix. HSCs can be activated in response to liver injury, and they differentiate to myofibroblasts, which greatly contribute to the fibrogenesis process. Various epigenetic procedures, including DNA methylation, histone modification and formation of particular chromatin structure, play crucial roles in the gene transcriptional expression in HSCs, regulating various vital processes. For instance, epigenetic modulation on the peroxisome proliferator-activated receptor gamma (PPAR-γ) gene promoter accounts for HSC differentiation through interacting pathways. Aberrant expression of a series of histones and chemokines in activated HSCs can aggravate inflammation and oxidative stress, which in turn promotes differentiation of HSCs to myofibroblasts and enhances the whole fibrogenesis process. Degradation of extracellular matrix is also regulated through epigenetic modulation on matrix associated enzymes. Moreover, fibrosis-related epigenetic modifications in the parental generation may be inherited to their offspring. In this review, we firstly summarize the vital epigenetic modifications of fibrosis-related genes in HSCs, and highlight specific nucleic acid sequences and structures in gene promoters as important action sites, which may provide indicators for liver fibrosis diagnosis in the future.


[Changes in blood flow after longitudinal stretching of the cat m. gastrocnemius].
Longitudinal stretch of the cat m. gastrocnemius by 10-30% of initial length increased the passive strength and regularly decreased the blood flow, the latter being dependent not on the degree of deformation but on the value of passive tension. Postelongation hyperemia develops after the stretch. This reaction seems to be similar to hyperemia due to the artery occlusion in the muscle and is considerably weaker than the postcontraction increase in the blood flow. The character of intramuscular mechanical effects on the vessels during both the active contractions and the passive stretch, is discussed.


Inflicted submersion in childhood.
To improve characterization and recognition of inflicted pediatric submersions. Retrospective case series, records review. A regional children's hospital and the King County (Washington) Medical Examiner's office. Children younger than 19 years who sustained submersion injury between 1983 and 1991 and were hospitalized or autopsied. Two pediatricians, using preestablished criteria, categorized abstracted case scenarios as either inflicted or unintentional events. The two groups were compared. Of 205 submersions, 16 (8%) were judged to have been inflicted. Objective physical signs of abuse and incompatibilities between the history and the child's stage of development or physical findings were common (69% and 50%, respectively). Inflicted submersion victims were likely to be young (median age, 2.1 years). They tended to be the youngest sibling in a large (three or more children) household. Social and demographic attributes of inflicted and unintentional submersion victims did not differ significantly. Bathtubs were the most common site for inflicted submersions (9/16 [56%]), and submersions in bathtubs were frequently inflicted (9/34 [26%]). Compared with unintentional submersion victims, children who were inflicted submersion victims were less likely to be revived by bystanders (relative risk, 0.10; confidence interval, 0.01 to 0.72) and were more likely to die (relative risk, 4.32; confidence interval, 1.40 to 21.43). Enough childhood submersions are inflicted to warrant careful case evaluation. Bathtub submersion victims and children with physical and historical findings common to other forms of abuse are most likely to be the victims of inflicted submersion.


A semi-automatic approach for epicardial adipose tissue segmentation and quantification on cardiac CT scans.
Many studies have shown that epicardial fat is associated with a higher risk of heart diseases. Accurate epicardial adipose tissue quantification is still an open research issue. Considering that manual approaches are generally user-dependent and time-consuming, computer-assisted tools can considerably improve the result repeatability as well as reduce the time required for performing an accurate segmentation. Unfortunately, fully automatic strategies might not always identify the Region of Interest (ROI) correctly. Moreover, they could require user interaction for handling unexpected events. This paper proposes a semi-automatic method for Epicardial Fat Volume (EFV) segmentation and quantification. Unlike supervised Machine Learning approaches, the method does not require any initial training or modeling phase to set up the system. As a further key novelty, the method also yields a subdivision into quartiles of the adipose tissue density. Quartile-based analysis conveys information about fat densities distribution, enabling an in-depth study towards a possible correlation between fat amounts, fat distribution, and heart diseases. Experimental tests were performed on 50 Calcium Score (CaSc) series and 95 Coronary Computed Tomography Angiography (CorCTA) series. Area-based and distance-based metrics were used to evaluate the segmentation accuracy, by obtaining Dice Similarity Coefficient (DSC) = 93.74% and Mean Absolute Distance (MAD) = 2.18 for CaSc, as well as DSC = 92.48% and MAD = 2.87 for CorCTA. Moreover, the Pearson and Spearman coefficients were computed for quantifying the correlation between the ground-truth EFV and the corresponding automated measurement, by obtaining 0.9591 and 0.9490 for CaSc, and 0.9513 and 0.9319 for CorCTA, respectively. In conclusion, the proposed EFV quantification and analysis method represents a clinically useable tool assisting the cardiologist to gain insights into a specific clinical scenario and leading towards personalized diagnosis and therapy.


Losartan in diabetic nephropathy.
Diabetic nephropathy has become the single most important cause of end-stage renal disease in the USA, Europe and Japan. The earliest marker of incipient diabetic nephropathy is the transition of normoalbuminuria to microalbuminuria at an albumin excretion rate of 20 microg/min. Human studies in patients both with and without diabetic kidney diseases have shown that the severity of baseline proteinuria is an important predictor of the rate of loss of renal function. Moreover, the reduction in protein excretion rate when patients with nephropathies are being treated with antihypertensive agents predicts the efficacy of subsequent renoprotection. Experimental and clinical observations provide the rationale for targeting the renin-angiotensin system as a renoprotective approach in diabetic and nondiabetic proteinuric nephropathies. Losartan (Cozaar, Merck Sharpe and Dohme) is a potent, orally active and highly specific angiotensin-type 1 receptor blocker. In addition to its antihypertensive efficacy, losartan decreases the left ventricular mass index in patients with hypertension, left ventricular end-diastolic and end-systolic volume in subjects with heart failure and prevents cardiovascular morbidity and death, predominantly stroke, independent of blood pressure reduction. Short-term studies in Type 1 diabetic patients with overt nephropathy have demonstrated that losartan and angiotensin-converting enzyme inhibitors have similar beneficial effects on albumin excretion rate, blood pressure and renal hemodynamics. Losartan also lowered albumin excretion rate in microalbuminuric patients with Type 2 diabetes mellitus. Moreover, the large multicenter Reduction of End points in Noninsulin dependent diabetes mellitus with the Angiotensin II Antagonist Losartan (RENAAL) trial has shown that blockade of angiotensin-type 1 receptor with losartan is superior to conventional antihypertensive therapy in slowing the progression of overt Type 2 diabetic nephropathy. Together, data from clinical trials demonstrate the beneficial effect of angiotensin-type 1 receptor blockers, including losartan, in the primary and secondary prevention of renal disease progression in diabetic patients. Nevertheless, it can be expected that the positive results achieved so far with this class of drugs may be further implemented by including angiotensin-type 1 receptor antagonists as a part of the multidrug approach that may hold more promise for the future of renoprotection in diabetic patients with chronic nephropathy.


Early sex-dependent differences in response to environmental stress.
Developmental plasticity enables the appearance of long-term effects in offspring caused by exposure to environmental stressors during embryonic and foetal life. These long-term effects can be traced to pre- and post-implantation development, and in both cases, the effects are usually sex specific. During preimplantation development, male and female embryos exhibit an extensive transcriptional dimorphism mainly driven by incomplete X chromosome inactivation. These early developmental stages are crucial for the establishment of epigenetic marks that will be conserved throughout development, making it a particularly susceptible period for the appearance of long-term epigenetic-based phenotypes. Later in development, gonadal formation generates hormonal differences between the sexes, and male and female placentae exhibit different responses to environmental stressors. The maternal environment, including hormones and environmental insults during pregnancy, contributes to sex-specific placental development that controls genetic and epigenetic programming during foetal development, regulating sex-specific differences, including sex-specific epigenetic responses to environmental hazards, leading to long-term effects. This review summarizes several human and animal studies examining sex-specific responses to environmental stressors during both the periconception period (caused by differences in sex chromosome dosage) and placental development (caused by both sex chromosomes and hormones). The identification of relevant sex-dependent trajectories caused by sex chromosomes and/or sex hormones is essential to define diagnostic markers and prevention/intervention protocols.


Activation of int-1 and int-2 mammary oncogenes in hormone-dependent and -independent mammary tumors of GR mice.
Mammary tumors in the GR mouse strain are caused by the expression of an endogenous provirus of the mouse mammary tumor virus (MMTV). The tumors progress from a hormone-dependent growth phase to autonomous, hormone-independent growth. We studied proviral insertion of MMTV at the int-1 and int-2 mammary oncogenes and the transcription of these genes during progression of a series of transplanted mammary tumors. During the hormone-dependent phase, 6 of 15 transplanted tumors were positive for proviral insertion at int-1 or int-2 or both. These tumors were oligoclonal with respect to the fraction of tumor cells with novel int-1 and int-2 restriction fragments and, apparently, consisted of different tumor cells with proviruses integrated at different oncogenes, including genes that are not yet known. In 10 tumors we detected expression of the int genes, indicating that most tumors contain minor populations of cells with int-1 or int-2 activations. On transplantation the tumors remained oligoclonal during the hormone-dependent phase. The hormone-independent variants of the tumors emerged as clonal outgrowths of cells with MMTV proviruses that could be traced back in the hormone-dependent tumors, but not always those of cells that were positive for insertions near int-1 or int-2. The maintenance of oligoclonality during the hormone-dependent phase suggests a growth-controlling effect of different populations of cells on each other. The clonal, hormone-independent tumors that arise later seem to be the result of mutations that are unrelated to int activation.


Discovery and phylogenetic analysis of a riverine species flock of African electric fishes (Mormyridae: Teleostei).
The evolution of species-specific mate recognition signals is of particular interest within speciose monophyletic groups with restricted distributions (known as "species flocks"). However, the explosive nature of speciation in these clades makes difficult the reconstruction of their phylogenetic history. Here we describe a species flock of riverine mormyrid fishes from west-central Africa in which electric signals may play a role in the reproductive isolation of sympatric species. In our recent field collections, totaling more than 1400 specimens from many localities, we recognize 38 forms that are distinct in their morphologies and electric organ discharge (EOD) characteristics. Of these 38, only four clearly correspond to described species. Here we treat these forms as operational taxonomic units (OTUs) in a phylogenetic analysis of cytochrome b sequence data from a sample of 86 specimens. We examined support in the molecular data for the monophyly of these 38 OTUs considered together, the monophyly of each phenotypically delimited OTU considered individually, and for relationships among OTUs congruent with those inferred from the distribution of morphological and EOD character states. Trees obtained by both maximum-parsimony and maximum-likelihood analyses, rooted with sequence data from outgroup taxa, provide evidence for the monophyly of these 38 OTUs with respect to other mormyrid fishes. The small genetic distances between many distinct forms suggest their recent divergence. However, in many instances the cytochrome b tree topology fails to support the monophyly of individual OTUs and close relationships between OTUs that are similar in morphology and EOD characteristics. In other cases, individuals from distinct OTUs share identical or nearly identical haplotypes. Close examination of these cases suggests that unnatural OTU definition is not the sole cause of this pattern, and we infer an incongruence between the mitochondrial gene tree and the organismal phylogeny caused by incomplete mitochondrial lineage sorting and/ or introgression across forms. The apparently rapid diversification in this clade of riverine electric fishes and the problems associated with recovering a meaningful species-level phylogeny from mitochondrial data parallel findings in other species flocks. Selection on EOD waveforms as mate recognition signals may be involved in the radiation of these fishes. This is the first description of a freshwater fish species flock from a riverine, as opposed to a lacustrine, environment.


Amplification and expression of c-Ki-ras oncogene in human ovarian cancer.
The amplification and expression of the cellular oncogene c-Ki-ras have been detected in twelve tissue specimens of human ovarian adenocarcinoma, one ascites of ovarian cancer and ovarian cancer cell line NIH: OVCAR-3. Four out of the twelve cancer tissue specimens, one specimen of cancer ascites cells and the NIH: OVCAR-3 cancer cell line showed elevated amplification of c-Ki-ras, as compared to the human fibroblast cell line FS4 and normal ovarian tissues. The amplification of the c-Ki-ras gene showed some correlation with clinical stages of ovarian cancer. The levels of c-Ki-ras specific RNA transcripts and ras gene product p21 were also elevated in these four cancer tissue specimens. Surprisingly, a discrepancy between amplification and expression of c-Ki-ras was noted in five of the other eight cancer tissue specimens, in which enhanced expression of c-Ki-ras was present without the accompanying elevated amplification of c-Ki-ras. The results do provide some clues to understanding the possible mechanisms of tumorigenesis in human ovarian cancer.


Antimalarial Activity of Crude Extract and Solvent Fractions of Leaves of Solanum nigrum L. (Solanaceae) against Plasmodium berghei in Mice.
Current malaria treatment is associated with continued development of drug resistance. Thus, there is a need to develop safe and effective new treatments from different sources. Solanum nigrum L. (Solanaceae) is a plant used for the treatment of malaria in Ethiopian traditional medicine. This study was aimed at evaluating of antimalarial activity of the crude extract and fractions of S. nigrum L. (Solanaceae) leaves against P. berghei infection in mice. Both prophylactic and suppressive models were used in evaluating antimalarial activity using the ANKA Plasmodium strain. In these models, male mice were randomly grouped into eleven groups (n = 5). Mice in group I were given 4% Tween-80, mice from group II up to X were given 100, 200, and 400 mg/kg of plant extract, and the last group (XI) was treated with chloroquine (25 mg/kg). Data were analyzed using one-way ANOVA followed by post hoc Tukey's multiple comparison test. Crude extract of leaves of S. nigrum showed chemosuppression of 30.68 (P < 0.05), 42.42 (P < 0.01), and 50.75% (P < 0.001) at 100, 200, and 400 mg/kg doses of the extract, respectively. At doses of 100, 200, and 400 mg/kg, the chloroform fraction produced a chemosuppressive effect of 40.15% (P < 0.01), 53.78% (P < 0.001), and 65.15% (P < 0.001) and a chemoprophylactic effect of 42.7% (P < 0.05), 51.84% (P < 0.001), and 67.17% (P < 0.001) when compared with negative control. In the suppressive model, the ethyl acetate fraction demonstrated a mean chemosuppression of 56.81% (P < 0.001), 65.9% (P < 0.001), and 70.83% (P < 0.001). Similarly, in the prophylactic model, the fraction showed suppression of 42.70% (P < 0.05), 53.11% (P < 0.001), and 71.03% (P < 0.001) at 100, 200, and 400 mg/kg doses. On the acute oral toxicity test, the extracts were safe at 2 g/kg dose. S. nigrum L. has antimalarial activity and supports the traditional medical practice.


Use of cross species genomic profiling identifies pathways and genes differentially regulated in prostate cancer cells treated with soy protein isolates or purified genistein.
The main purified compound from soy protein isolates is genistein, but this purified phytoestrogen fails to recapitulate all the features of the soy-based diet that is associated with lower incidence of prostate cancer. Rat and human prostate cancer cell lines were treated with either soy protein isolates or purified genistein. In vitro cell growth was correlated with the associated genomic expression profiles using cDNA arrays. The data was subsequently bioinformatically analyzed within and across species to identify common changes in expression profiles associated with the soy protein or genistein treatments. Gene expression profiling and data mining noted genes specific to soy; however, biological pathways showed the same gene regulation profiles between genistein and soy. Genistein is likely the major contributor to the effect of soy proteins on cellular pathways; however, the expression of different genes using soy protein isolates suggests complexity in the many compounds found in whole soy protein.


Severe neuropathy with leaky connexin32 hemichannels.
X-linked Charcot-Marie-Tooth disease is one of a set of diseases caused by mutations in gap junction proteins called connexins. We identified a connexin32 missense mutation (F235C) in a girl with unusually severe neuropathy. The localization and trafficking of the mutant protein in cell culture was normal, but electrophysiological studies showed that the mutation caused abnormal hemichannel opening, with excessive permeability of the plasma membrane and decreased cell survival. Abnormal leakiness of connexin hemichannels is likely a mechanism of cellular toxicity in this and perhaps other diseases caused by connexin mutations.


Stroke surfaces: temporally coherent artistic animations from video.
The contribution of this paper is a novel framework for synthesizing nonphotorealistic animations from real video sequences. We demonstrate that, through automated mid-level analysis of the video sequence as a spatiotemporal volume--a block of frames with time as the third dimension--we are able to generate animations in a wide variety of artistic styles, exhibiting a uniquely high degree of temporal coherence. In addition to rotoscoping, matting, and novel temporal effects unique to our method, we demonstrate the extension of static nonphotorealistic rendering (NPR) styles to video, including painterly, sketchy, and cartoon shading. We demonstrate how this novel coherent shading framework may be combined with our earlier motion emphasis work to produce a comprehensive "Video Paintbox" capable of rendering complete cartoon-styled animations from video clips.


Ovulation rate and pre- and postimplantation survival in mice with a major gene for rapid postweaning gain.
Differences in ovulation rate, embryo survival, litter size, and fertility are presented for four lines of mice that have been selected for growth or are homozygous for a recessive gene (hg) imparting rapid postweaning gain. Two of the lines were hg/hg, one in a growth-neutral and one in a growth-selected background. The remaining two were Hg/Hg (the corresponding normal, dominant allele with no effect on postweaning gain) in the same two backgrounds. Average ovulation rates ranged from 10.9 to 17.1 eggs shed, and litter sizes ranged from 8.6 to 14.0. In the growth-selected background, the hg allele reduced the number of ovulations, implantation, and litter size by nearly three compared with the Hg/Hg controls. The impact of the hg allele in the growth-neutral background was not significant. When males of a different line selected for high litter size were mated to females of the four stocks, more than two additional eggs, implants, and pups were recorded, compared with results of mating to males of the same line as the female.


[Lymphogranulomatosis: a systems analysis of the age- and sex-related characteristics of hemopoiesis and metabolism].
72 clinical and laboratory features were analyzed on the IBM PC 486 for 126 new cases of lymphogranulomatosis prior to treatment. Myelograms were found to vary with sex and age of the patients demonstrating close relations between hemopoiesis and processes in the lymph nodes. In males maturation of myeloid elements KM was inhibited, though they had more monocytes KM. These monocytes got more numerous in unfavorable histological variants and generalization. Lymphopenia and monocytosis were more pronounced in patients under 30 becoming more severe in generalization and intoxication. Age-related changes in cholesterol in lymphogranulomatosis patients were abnormal: in older patients cholesterol was low. This phenomenon is extremely unfavorable. The findings elucidate prognostic value of sex and age in lymphogranulomatosis and suggest a hypothesis that monocytes (macrophages) and secreted by them monokines are responsible for specific intoxication, neutrophilia and lymphopenia. Berezovsky-Sternberg cells may be hybrids of macrophages and B-lymphocytes.


Polypeptide toxins from the venoms of Old World and New World scorpions preferentially block different potassium channels.
Venoms from five Old World and two New World scorpions were tested for their ability to block various K+ channels in rat brain synaptosomes. A 86Rb efflux kinetic assay was used to identify three types of K+ channels, Ca(2+)-independent, voltage-gated, inactivating (A-type) and noninactivating (delayed rectifier) K+ channels and Ca(2+)-activated K+ channels [J. Physiol. (Lond.) 361:419-440, 441-457 (1985)]. The venoms from the Old World scorpions all blocked the A-type K+ channel but not the delayed rectifier K+ channel; only venom from the Israeli scorpion, Leiurus quinqestriatus hebraeus (Lqh), blocked the Ca(2+)-activated K+ channel. In contrast, venoms from the two New World scorpions selectively blocked the delayed rectifier K+ channel. Water-soluble components from Lqh venom from the Brazillian scorpion, Tityus serrulatus (Ts), were separated by ion exchange high performance liquid chromatography (HPLC). Seven components that blocked synaptosome K+ channels were isolated from Lqh venom by ion exchange HPLC. All seven components blocked the A-type K+ channel; the five most potent toxins had IC50 values of 18-40 nM. Two of the components from Lqh venom (one identified as charybdotoxin and the other denoted as Lqk4) also blocked a Ca(2+)-activated K+ channel (IC50 = 15 and 60 nM for charybdotoxin and Lqk4, respectively). Five K+ channel-blocking components were isolated from the Ts venom; all five blocked the delayed rectifier channel selectively, and the two most potent components had IC50 values of 8 and 30 nM. Several of the more potent Lqh and Ts toxins were purified to near-homogeneity by reverse phase HPLC. These toxins should be useful as ligands for K+ channel purification, for elucidation of K+ channel structure, and for studies of K+ channel function.


Microtubule behavior during guidance of pioneer neuron growth cones in situ.
The growth of an axon toward its target results from the reorganization of the cytoskeleton in response to environmental guidance cues. Recently developed imaging technology makes it possible to address the effect of such cues on the neural cytoskeleton directly. Although high resolution studies can be carried out on neurons in vitro, these circumstances do not recreate the complexity of the natural environment. We report here on the arrangement and dynamics of microtubules in live neurons pathfinding in response to natural guidance cues in situ using the embryonic grasshopper limb fillet preparation. A rich microtubule network was present within the body of the growth cone and normally extended into the distal growth cone margin. Complex microtubule loops often formed transiently within the growth cone. Branches both with and without microtubules were regularly observed. Microtubules did not extend into filopodia. During growth cone steering events in response to identified guidance cues, microtubule behaviour could be monitored. In turns towards guidepost cells, microtubules selectively invaded branches derived from filopodia that had contacted the guidepost cell. At limb segment boundaries, microtubules displayed a variety of behaviors, including selective branch invasion, and also invasion of multiple branches followed by selective retention in branches oriented in the correct direction. Microtubule invasion of multiple branches also was seen in growth cones migrating on intrasegmental epithelium. Both selective invasion and selective retention generate asymmetrical microtubule arrangements within the growth cone, and may play a key role in growth cone steering events.


Proteolytic mechanism of a novel mitochondrial and chloroplastic PreP peptidasome.
The 2.1-A-resolution crystal structure of the novel mitochondrial and chloroplastic metalloendopeptidase, AtPreP1, revealed a unique peptidasome structure, in which the two halves of the enzyme completely enfold a huge proteolytic cavity. Based on the structure, we proposed a novel mechanism for proteolysis involving hinge-bending motions, which cause the protease to open and close in response to substrate binding. We generated four double-mutants of AtPreP1 by introducing cysteines at positions where disulfide bonds can be formed in order to lock and unlock the protease and tested the activity under oxidizing and reducing conditions. The overall results support the proposed mechanism.


Hypertonic saline treatment of uncontrolled hemorrhagic shock at different periods from bleeding.
Hypertonic saline has been recently recommended for treatment of patients in hemorrhagic shock. Infusion of hypertonic saline at different periods in cases of uncontrolled hemorrhagic shock was studied in rats. The animals were divided into six groups: in group 1 uncontrolled hemorrhagic shock was induced by tail resection and no hypertonic saline was administered; in group 2 hypertonic saline was administered 5 minutes after shock was induced; in group 3 hypertonic saline was administered 15 minutes after shock was induced; in group 4 hypertonic saline was administered 30 minutes after shock was induced; in group 5 hypertonic saline was administered 60 minutes after shock was induced; and in group 6 hypertonic saline was administered 120 minutes after shock was induced. Tail resection in rats in group 1 was followed by a mean +/- SEM bleeding of 2.7 +/- .03 mL in 5 minutes. Infusion of hypertonic saline after 5 and 15 minutes resulted in additional bleeding of 6.3 +/- 1.0 mL and 3.8 +/- 0.5 mL, respectively, and a drop in mean arterial pressure to 36 +/- 8 mm Hg and 56 +/- 9 mm Hg, respectively. Mortality was 80% in group 2 and 53% in group 3. Infusion of hypertonic saline 30 and 60 minutes after shock was induced did not alter bleeding, mean arterial pressure, or survival. Infusion of hypertonic saline within 15 minutes of hemorrhagic shock resulted in increased bleeding, hypotension, and early death. Infusion 30 minutes or later did not alter these variables. This potential danger of early hypertonic saline therapy should be considered in the treatment of patients in trauma.


Irinotecan in combined-modality therapy for locally advanced non-small-cell lung cancer.
The management of non-small-cell lung cancer is undergoing rapid evolution. Although the advent of combined-modality therapy has led to improved survival, most patients eventually succumb to the disease. The arrival of a new generation of chemotherapeutic agents--including the taxanes, gemcitabine (Gemzar), and topoisomerase inhibitors such as irinotecan (Camptosar, CPT-11)--offers the hope of advances against this malignancy. Irinotecan, a camptothecin derivative, has shown impressive activity in a variety of solid tumors, including non-small-cell lung cancer. It is believed to act by stabilizing the topoisomerase-DNA complex formed during diverse cellular processes, including replication and transcription. A considerable body of evidence also demonstrates that camptothecin and its derivatives possess substantial radiosensitization properties. This article will review the in vitro and in vivo data on irinotecan's ability to render tumors more susceptible to ionizing radiation. It will then focus on experience with irinotecan and thoracic radiation in the treatment of non-small-cell lung cancer, which has yielded acceptable toxicity results and response rates in excess of 60% in early trials. It is hoped that newer treatment strategies--such as the combination of radiation and irinotecan in lung cancer--will significantly impact cure rates in the future.


Medicine is Patriarchal, But Alternative Medicine is Not the Answer.
Women are over-represented within alternative medicine, both as consumers and as service providers. In this paper, I show that the appeal of alternative medicine to women relates to the neglect of women's health needs within scientific medicine. This is concerning because alternative medicine is severely limited in its therapeutic effects; therefore, those who choose alternative therapies are liable to experience inadequate healthcare. I argue that while many patients seek greater autonomy in alternative medicine, the absence of an evidence base and plausible mechanisms of action leaves patients unable to realize meaningful autonomy. This seems morally troubling, especially given that the neglect of women's needs within scientific medicine seems to contribute to preferences for alternative medicine. I conclude that the liberatory credentials of alternative medicine should be questioned and make recommendations to render scientific medicine better able to meet the needs of typical alternative medicine consumers.


[Bilateral vestibular loss as a post-infection complication of yersiniosis?].
Yersinia infections other than plaque are caused by Yersinia pseudotuberculosis and Yersinia enterocolitica. Food and water contamination as well as animal-to-person and person-to-person contact are common pathways of transmission. Clinical manifestations include enteritis, enterocolitis, acute appendicitis, inflammation of the terminal ileum, and mesenteric adenitis. Y. enterocolitica may cause bacteremia with subsequent septicemia predominantly in patients with underlying illnesses such as diabetes mellitus or malignancy. More frequently enteritis is followed by immunological post-infectious syndromes such as arthritis and erythema nodosum. The present case report discusses bilateral vestibular loss possibly caused by an infection with Y. enterocolitica. A 27-year-old caucasian woman initially presented with the otologic symptom of spinning vertigo accompanied by nausea and vomiting. Physical exam revealed spontaneous nystagmus to the left. Bithermal caloric responses were absent. Pure tone audiometry showed a bilateral symmetric high-frequency sensorineural hearing loss. Neurologic exams did not reveal involvement of the central vestibular system. Perilymphatic fistula on the left side was excluded by tympanoscopy. Serology for rheumatoid factors and HLA B27 was negative. Lead or mercury intoxication was also excluded. In her medical history the patient reported intermittent watery diarrhea and stress dependent arthralgia that had commenced during a stay in Argentina three years ago. Serology was positive, revealing elevated titers for Y. enterocolitica type 3 (1:200) and type 9 (1:400). Bilateral vestibular loss is rare. The main cause is aminoglycoside ototoxicity or meningitis. Yersina infections have not yet been described as inducing disease of the labyrinth. Present pathophysiologic knowledge of yersinia infections is described as follows: After peroral infection, gastrointestinal permeability is increased. Low-molecular-weight substances may enter the bloodstream and stimulate the formation of circulating immune complexes. These are held responsible for extraintestinal manifestations of yersinosis. Whether these circulating immune complexes and antibodies against Y. enterocolitica have an effect on the inner ear remains unclear. Because the coincidence of yersiniosis and a bilateral vestibular loss with no other identified cause, a postinfectious immune response is suggested as possible pathogenic mechanism.


The preoperative bleeding time test lacks clinical benefit: College of American Pathologists' and American Society of Clinical Pathologists' position article.
The major conclusions of this position article are as follows: (1) In the absence of a history of a bleeding disorder, the bleeding time is not a useful predictor of the risk of hemorrhage associated with surgical procedures. (2) A normal bleeding time does not exclude the possibility of excessive hemorrhage associated with invasive procedures. (3) The bleeding time cannot be used to reliably identify patients who may have recently ingested aspirin or nonsteroidal anti-inflammatory agents or those who have a platelet defect attributable to these drugs. The best preoperative screen to predict bleeding continues to be a carefully conducted clinical history that includes family and previous dental, obstetric, surgical, traumatic injury, transfusion, and drug histories. A history suggesting a possible bleeding disorder may require further evaluation; such an evaluation may include performance of the bleeding time test, as well as a determination of the platelet count, the prothrombin time, and the activated partial thromboplastin time. In the absence of a history of excessive bleeding, the bleeding time fails as a screening test and is, therefore, not indicated as a routine preoperative test.


Smoking history and aging-associated cognitive decline: An event-related brain potential study.
Although cigarette smoking has been associated with reduced risk for dementia of the Alzheimer type, relatively little is known about the central impact of a lengthy smoking history, particularly with respect to the cognitive effects, on the normal aging brain. Given that elderly adults have been reported to exhibit poor short-term memory in conditions requiring divided attention, this study utilized behavioral performance and event-related potential (ERP) measures to compare groups (n = 10/group) of young (18-39 years) and elderly (64-81 years) adult smokers and nonsmokers during a continuous visual word recognition task carried out alone and concurrently with an auditory (oddball) tone discrimination task. Young and elderly adult smokers had average smoking histories of 9.3 and 52.0 years, respectively. Significant aging (young > elderly adults) and task (single-task > dual-task) effects were observed for performance accuracy and speed measures as well as for N400/P600 ERP waveform components elicited by 'old/new' word recognition and P300 ERP indices elicited by auditory target detection. The effects of smoking history were limited to the P600 component, which showed faster latencies in elderly smokers than elderly nonsmokers and young nonsmokers. Young smokers exhibited longer latencies than young nonsmokers. The results were discussed in relation to normal and pathological cognition in the elderly.


Clostridium difficile Toxin B causes epithelial cell necrosis through an autoprocessing-independent mechanism.
Clostridium difficile is the most common cause of antibiotic-associated nosocomial infection in the United States. C. difficile secretes two homologous toxins, TcdA and TcdB, which are responsible for the symptoms of C. difficile associated disease. The mechanism of toxin action includes an autoprocessing event where a cysteine protease domain (CPD) releases a glucosyltransferase domain (GTD) into the cytosol. The GTD acts to modify and inactivate Rho-family GTPases. The presumed importance of autoprocessing in toxicity, and the apparent specificity of the CPD active site make it, potentially, an attractive target for small molecule drug discovery. In the course of exploring this potential, we have discovered that both wild-type TcdB and TcdB mutants with impaired autoprocessing or glucosyltransferase activities are able to induce rapid, necrotic cell death in HeLa and Caco-2 epithelial cell lines. The concentrations required to induce this phenotype correlate with pathology in a porcine colonic explant model of epithelial damage. We conclude that autoprocessing and GTD release is not required for epithelial cell necrosis and that targeting the autoprocessing activity of TcdB for the development of novel therapeutics will not prevent the colonic tissue damage that occurs in C. difficile - associated disease.


Cigarette smoking and lung cancer cell types.
The role of tobacco smoke in the development of lung cancer is well known for squamous and small cell types, somewhat less so for adenocarcinoma, and not specifically assessed for large cell carcinoma. In the current analysis, based on 851 men and 507 women with lung cancer and their matched controls (888 men and 608 women), smoking was associated with each lung cancer cell type, and differences in smoking habits by cell types were small. However, the increase of lung cancer risk according to number of cigarettes per day was stronger for small cell and oat cell carcinoma than for adenocarcinoma. There was no increase for large cell carcinoma. For squamous cell carcinoma, this dose response was weak among men and strong among women. The strength of the association between smoking and lung cancer cell types may be related to cancer location, with more peripheral lung cancer types (such as adenocarcinoma and large cell carcinoma) showing weaker associations than more central tumors (such as squamous or small cell and oat cell carcinoma).


Distribution of two model amino acids from cerebrospinal fluid to brain and blood.
Ventriculocisternal perfusions of anesthetized rabbits were performed for 1-3 h with solutions containing radioactively labeled alpha-aminoisobutyric acid (AIB), cycloleucine (CYCL), and sucrose. Serial brain samples were taken at the conclusion of the perfusion period and assayed for radioactivity. Tissue concentration profiles were constructed from these data; tissue distribution spaces and diffusion coefficients (Dt) plus brain capillary transfer constants were estimated from the profiles. The Dt of sucrose was somewhat larger at 1 h than at 2 and 3 h. Tissue distribution spaces of 300-400% were found with AIB after 3 h. Inclusion of 5 mM AIB in the perfusate produced markedly lower tracer AIB spaces. The tissue distribution spaces of CYCL ranged from 100 to 400% and depended on the concentration of CYCL in the perfusate. A brain-to-blood transfer half time of 7.5 min was measured for CYCL. These findings demonstrate that sizable cellular uptake of CYCL and AIB occurs, that these processes are concentration dependent, and that the rates of influx and efflux across brain capillaries are similar.