Bordetella parapertussis survives inside human macrophages in lipid raft-enriched phagosomes.
Bordetella parapertussis is a human pathogen that causes whooping cough. The increasing incidence of B. parapertussis has been attributed to the lack of cross protection induced by pertussis vaccines. It was previously shown that B. parapertussis is able to avoid bacterial killing by polymorphonuclear leukocytes (PMN) if specific opsonic antibodies are not present at the site of interaction. Here, we evaluated the outcome of B. parapertussis innate interaction with human macrophages, a less aggressive type of cell and a known reservoir of many persistent pathogens. The results showed that in the absence of opsonins, O antigen allows B. parapertussis to inhibit phagolysosomal fusion and to remain alive inside macrophages. The O antigen targets B. parapertussis to lipid rafts that are retained in the membrane of phagosomes that do not undergo lysosomal maturation. Forty-eight hours after infection, wild-type B. parapertussis bacteria but not the O antigen-deficient mutants were found colocalizing with lipid rafts and alive in nonacidic compartments. Taken together, our data suggest that in the absence of opsonic antibodies, B. parapertussis survives inside macrophages by preventing phagolysosomal maturation in a lipid raft- and O antigen-dependent manner. Two days after infection, about 15% of macrophages were found loaded with live bacteria inside flotillin-enriched phagosomes that had access to nutrients provided by the host cell recycling pathway, suggesting the development of an intracellular infection. IgG opsonization drastically changed this interaction, inducing efficient bacterial killing. These results highlight the need for B. parapertussis opsonic antibodies to induce bacterial clearance and prevent the eventual establishment of cellular reservoirs of this pathogen.


Discrete patterns of cortical thickness in youth with bipolar disorder differentially predict treatment response to quetiapine but not lithium.
The need for treatment response predictive biomarkers is being increasingly recognized in children and adolescents with psychiatric disorders. Structural gray matter abnormalities as a predictor of treatment outcome in pediatric bipolar disorder have not been systematically investigated, especially early in the illness course. With a prospective longitudinal study design, the present study enrolled 52 bipolar adolescents with no history of treatment with mood stabilizers or a therapeutic dose of antipsychotic drugs and 31 healthy controls. Patients were randomly assigned to treatment with quetiapine or lithium after pretreatment data collection. A hierarchical cluster analysis was performed using pretreatment cortical thickness data that identified two discrete patient subgroups. Compared to healthy subjects, patients in subgroup 1 (n = 16) showed widespread greater cortical thickness mainly across heteromodal cortex but also involving some regions of unimodal cortex, while those in subgroup 2 (n = 36) showed regional cortical thinning mainly in superior temporal and superior parietal regions. Patients within subgroup 1 showed a significantly higher response rate to quetiapine than those in subgroup 2 (100% vs 53%). No statistically significant difference was found in lithium response rate between the patient subgroups (63% vs 53%). Pretreatment clinical ratings and neuropsychological data did not differ across subgroups. Our findings suggest the existence of distinct and clinically relevant subgroups of pediatric bipolar patients, as defined by pattern of cortical thickness. These groups appear to differentially respond to antipsychotic treatment-notably with greater cortical thickness relative to controls predicting better treatment response.


A national study on nurses' retention in healthcare facilities in underserved areas in Lebanon.
Nursing shortages and maldistribution are priority issues for healthcare systems around the globe. Such imbalances are often aggravated in underserved areas, especially in developing countries. Despite the centrality of this issue, there is a dearth of studies that examine the retention of nurses in underserved areas in the Middle East Region. This study investigates the characteristic and the factors associated with the retention of nurses working in rural areas in Lebanon. This study uses a non-experimental cross-sectional design to survey nurses working in underserved areas of Lebanon. Underserved areas in Lebanon were identified using WHO definition. A total of 103 health facilities (hospitals and primary healthcare centers) located in these areas were identified and all nurses working at these facilities received a copy of the survey questionnaire. The questionnaire included five sections: demographic, work-life, career plan, job satisfaction, and assessment of work environment. Analysis included univariate and bivariate (chi-square, Student's t-test and ANOVA) tests to describe the respondents and examine the significance between nurses' characteristics and their intent to stay. A logistic regression model was constructed to identify factors associated with nurses' intent to stay in underserved areas. A total of 857 nurses from 63 Primary Healthcare (PHC) centers and hospitals responded to the questionnaire (75.5% response rate). Only 35.1% of nurses indicated their intent to stay in their current job over the coming one to three years. Surveyed nurses were most satisfied with relationship with co-workers and least satisfied with extrinsic rewards. Rural nurses working in PHC centers were more satisfied than their hospital counterparts on all aspects of work and had significantly higher intention to stay (62.5% compared to 31.5% in hospitals, P < 0.001). Regression analysis revealed that nurses less likely to report intent to stay were younger, unmarried, with less years of work experience and were not working towards a higher degree. Analysis reveals a directly proportional relationship between nurses' reported job satisfaction and their intent to stay. This study reveals poor retention of nurses in rural and underserved areas in Lebanon, especially in the hospital sector. The status quo is disquieting as it reflects an unstable and dissatisfied nursing workforce. Developing targeted retention strategies for younger nurses and those working in hospitals as well as the offering of professional development opportunities and devising an incentive scheme targeting rural nurses is pivotal to enhance nurses' job satisfaction and retention in rural settings.


Vitamin D and Respiratory Diseases : Based on 11th Dr. I. C. Verma Excellence in Research Award for Young Pediatricians Delivered as Oration on 15th Oct. 2023.
The significance of Vitamin D has been appreciated beyond bone health and calcium metabolism. The importance of Vitamin D in respiratory health has been recognized due to its immunomodulatory and anti-microbial properties. The hypothesis is that Vitamin D could have a significant role in the pathogenesis of respiratory diseases and may represent a novel preventive and therapeutic strategy. Furthermore, enumerable observational studies established the association of Vitamin D deficiency with respiratory diseases such as asthma, bronchiolitis, pneumonia, tuberculosis, etc. However, experimental studies have not shown the encouraging results. This brief review will summarize and discuss the synthesis and metabolism of Vitamin D, the prevalence of Vitamin D deficiency in children, its role in the pathogenesis of various childhood respiratory diseases, and an overview of the therapeutic trials assessing the role of Vitamin D supplementation in childhood respiratory diseases.


[The use of a calcium phosphate ceramic in treating deep caries].
Clinical examinations of 36 teeth with deep caries were carried out in patients aged 16 to 38. Therapy with hydroxyl apatite and tricalcium phosphate was carried out and with calmecine for control. Additional methods for objective examination were assessment of pulp electric excitability and of dentin electric conduction. Repeated examinations of patients 1 and 6 months after treatment showed that hydroxyl apatite and tricalcium phosphate normalized the function of the pulp, caused remineralization of dentin in the bottom of carious cavity, and were effective in the treatment of deep caries.


Optic nerve damage in human glaucoma. III. Quantitative correlation of nerve fiber loss and visual field defect in glaucoma, ischemic neuropathy, papilledema, and toxic neuropathy.
The number and distribution of human optic nerve axons were compared with clinical measurements available the same eyes, including visual acuity, disc appearance, and visual field studies. Definite loss of axons occurs prior to reproducible visual field defects in some patients suspected of having glaucoma. In glaucoma, the superior and inferior poles of the nerve lose nerve fibers at a selectively greater rate, leading to an hourglass-shaped atrophy. Cavernous degeneration of the retrobulbar optic nerve is rarely observed in chronic glaucoma. The pattern of atrophy in examples of toxic amblyopia, ischemic optic neuropathy and chronic papilledema differ from that of glaucoma, suggesting different mechanisms of damage in these conditions.


Compromised extinction and signal-to-noise ratios of weak-resonant-cavity laser diode transmitter injected by channelized and amplitude squeezed spontaneous-emission.
By using a 200GHz AWG channelized ASE source in connection with a saturable semiconductor optical amplifier (SOA) based noise blocker as the injecting source at the remote node in front of the local optical network units (ONUs), we demonstrate the spectrum-sliced ASE transmitter with greatly suppressed intensity noise performance in WDM-PON network. Such channelized SOA filtering technique effectively reduces the relative intensity noise of the ASE source by at least 4.5 dB. The low-noise WRC-FPLD transmitter improves its extinction-ratio (ER) from 8.9 to 9.6 dB and signal-to-noise ratio (SNR) from 5.9 to 6.3 dB. In comparison with broad-band ASE injection-locked WRC-FPLD transmitter at same power, there is an improvement on receiving power penalty (DeltaP(Receiver)) by 2 dB at BER 10(-9) in back-to-back case, and the receiving power of BER 10(-9) can achieve -24 dBm even after 25km fiber transmission. With additional AWG filtering, the intraband crosstalk effect between the upstream transmitted data and the reflected ASE signal is significantly reduced by 6.3dB. The compromised effects of ER and SNR on BER performance are also elucidated via the modified SNR model for the WRC-FPLD under ASE injection induced gain-saturation condition. The DeltaP(Receiver)/DeltaSNR of 8.89 at same ER condition is more pronounced than the DeltaP(Receiver)/DeltaER of 3.17 obtained under same SNR condition, indicating that the SNR plays a more important role than the ER on enhancing the BER performance.


Pirogliride: an oral hypoglycemic drug which accelerates glucose usage and insulin secretion by islets of Langerhans.
Pirogliride potentiates glucose-induced insulin secretion from isolated islets. This effect is accompanied by a facilitated glucose metabolism. Pirogliride partially prevents the known inhibitory effects of mannoheptulose on glucose-induced secretion and utilization. Pirogliride might be useful not only to probe the underlying mechanism of stimulated insulin secretion but also in the therapy of those diabetics who have an impaired beta-cell responsiveness to glucose.


Molecular definition of a major cytotoxic T-lymphocyte epitope in the glycoprotein of lymphocytic choriomeningitis virus.
Analyses with segmental reassortants of lymphocytic choriomeningitis virus (LCMV) RNA have shown that cytotoxic T lymphocytes (CTL) are induced by and recognize proteins encoded by the viral short segment, which specifies two virus structural proteins, glycoprotein (GP) and nucleoprotein (NP). Expression of cDNA copies of these genes in vaccinia virus vectors demonstrates that C57BL/6 (H2bb) mice mount significant CTL responses to both GP and NP. We have used LCMV-specific H2bb-restricted CTL clones and a family of serial C-terminal truncations of the LCMV GP expressed in vaccinia virus to map the precise specificities of the anti-GP clones. Of the 18 CTL clones studied, 1 recognizes NP and the other 17 recognize GP. The reactivities of 14 of the 17 anti-GP CTL clones against the deleted GP molecules have been fully characterized, and two clear patterns of anti-GP activity have emerged, defining at least two CTL epitopes. The first epitope, recognized by only two of the clones, lies within GP residues 1 to 218. The second is recognized by all 12 of the remaining clones and was mapped, by using the GP deletions, to a 22-amino-acid region comprising GP residues 272 to 293. A synthetic peptide representing this area sensitized uninfected syngeneic target cells to lysis both by bulk CTL obtained from the spleen after a primary immunization and by appropriate CTL clones. Two sets of criteria are available which are said to identify potential T-cell epitopes, one based on primary amino acid sequence and the second based on protein secondary structure. Neither of these predictive schemes would have identified region 272 to 293 as a CTL recognition motif, indicating that such programs are of limited usefulness as presently conceived. Analysis of the CTL clones shows clearly that all three families (anti-NP and anti-GP 1 to 218 and 272 to 293) direct efficient cross-reactive killing against a variety of serologically distinct strains of LCMV.


Immunomodulatory Drugs in Melanoma Brain Metastases.
Brain metastases are about ten times more frequent than a brain primary tumor, being present in 20-40% of adults with systemic cancer. Together with lung cancer and breast cancer, skin cancers such as melanoma are top primary tumors which metastasizes to the brain. Advanced melanoma is well known for its propensity to metastasize to the brain, with 80% of patients presenting brain metastasis at the autopsy. However, current therapies are not very efficient and brain metastases are in most of the cases lethal. Treatment of melanoma brain metastases with surgery and/or radiation therapy results in a median overall survival of only about four months after diagnosis. New immunotherapies such as targeted or immunomodulatory drugs, many in clinical trials, have shown promise, with some immunomodulatory drugs being able to at least double the overall survival rates for patients with melanoma brain metastases. This review focuses on the recent advances and future potential of using immunotherapy, such as the newly developed immunomodulatory drugs, for melanoma brain metastases therapy. Immunomodulatory drugs bring a great promise as new tools for melanoma treatment in particular and for the treatment of other types of malignancies in general.


Therapeutic strategy of emergency surgery for colon cancer in 71 patients over 70 years of age in Japan.
The prognosis for colon cancer is poorest in cases of emergency situation in the elderly not only in Japan, but worldwide. The aim was to design a therapeutic approach used for colon cancer in the elderly. Seventy-one patients, who were all older than 70 years, with colon carcinoma in an emergency situation were examined. Lethality, surgical procedure, risk of comorbidity, multiple organ system failure and the effect of endotoxin absorption were examined. Any increase in comorbidity was associated with a higher clinical lethality in the lungs, heart, kidney, and diabetes. The highest postoperative mortality rate was recorded in patients who underwent primary resection after perforation, while the lowest postoperative mortality rate was recorded in patients who underwent primary resection after obstruction. Postoperative failure of the lungs and heart and renal failure were associated with a significantly higher mortality rate. Twenty-five septic patients received an endotoxin adsorption due to blood filtration and 8 patients survived. Of the eight survivors, the endotoxin concentration was significantly decreased by an endotoxin absorption. In cases of ileus, the resection may be performed positively. In cases of perforation, we may safely say now that stoma and resection is to be recommended. Endotoxin absorption due to blood filtration may be an effective additional therapy for post-operative septic shock.


Molecular profiling and prognostic relevance of circulating tumor cells in the blood of ovarian cancer patients at primary diagnosis and after platinum-based chemotherapy.
Disseminated tumor cells (DTCs) in the bone marrow (BM) were shown to be of prognostic significance in gynecological cancers. Bone marrow aspiration is less accepted by patients compared with blood drawing. In this pilot study, we applied the AdnaTest BreastCancer based on immunomagnetic enrichment, targeting common antigens on epithelial gynecological cancers, followed by multiplex reverse transcriptase-polymerase chain reaction for selection and detection of circulating tumor cells (CTCs) in the blood of 122 ovarian cancer patients at primary diagnosis and/or after platinum-based chemotherapy. Results were compared with detection of DTC in BM. Ten-milliliter blood was obtained before surgery (n=86) and/or after chemotherapy (n=70) and analyzed for CTC with the AdnaTest BreastCancer for the detection of EpCAM-, MUC-1-, and HER-2-transcripts. CA 125 was assessed in an additional single-plex reverse transcriptase-polymerase chain reaction. Bone marrow aspirates were analyzed in duplicate by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. Before surgery, CTCs were detected in 19% of patients, expressing EpCAM (31%), MUC-1 (50%), HER-2 (31%), and CA 125 (50%), respectively. After chemotherapy, the overall detection rate for CTC was 27%, thereof EpCAM (68%), MUC-1 (47%), HER2 (21%), and CA 125 (37%). The overall detection rate for DTC in the BM was 35% before surgery and 31% after therapy. A comparison between DTC and CTC resulted in a concordance rate of 59% before surgery and 56% after chemotherapy. CTC positivity significantly correlated with shorter overall survival before surgery (P=0.0054) and after chemotherapy (P=0.047). This methodological approach might help to identify molecular targets for specific biological therapies. Blood analysis could give additional information complimentary to that obtained by DTC.


Effects of metals on life cycle parameters of the earthworm Eisenia fetida exposed to field-contaminated, metal-polluted soils.
Two control and eight field-contaminated, metal-polluted soils were inoculated with Eisenia fetida (Savigny, 1826). Three, 7, 14, 21, 28 and 42 days after inoculation, earthworm survival, body weight, cocoon production and hatching rate were measured. Seventeen metals were analysed in E. fetida tissue, bulk soil and soil solution. Soil organic carbon content, texture, pH and cation exchange capacity were also measured. Cocoon production and hatching rate were more sensitive to adverse conditions than survival or weight change. Soil properties other than metal concentration impacted toxicity. The most toxic soils were organic-poor (1-10 g C kg(-1)), sandy soils (c. 74% sand), with intermediate metal concentrations (e.g. 7150-13,100 mg Pb kg(-1), 2970-53,400 mg Zn kg(-1)). Significant relationships between soil properties and the life cycle parameters were determined. The best coefficients of correlation were generally found for texture, pH, Ag, Cd, Mg, Pb, Tl, and Zn both singularly and in multivariate regressions. Studies that use metal-amended artificial soils are not useful to predict toxicity of field multi-contaminated soils.


Microplastics in fishes of commercial and ecological importance from the Western Arabian Gulf.
Microplastic particles (MPs) in the gastrointestinal tracts of nine fish species of commercial importance from different habitats (coastal, pelagic, and reef-associated) in the Saudi EEZ of the Arabian Gulf were quantified and classified. A total of eight MPs were retrieved from a total of 140 individual fish examined, with an average of 0.057 ± 0.019 microplastic items per fish (excluding possible plastic fibers). On average, 5.71%, of the fish dissected contained MPs, ranging from 5 to 15% of individual fish examined containing MPs among species (Siganus canaliculatus and Rastrelliger kanagurta, respectively). Ingested plastic consisted primarily of fishing threads (1.04 ± 0.06 mm), followed by fragments (1.16 ± 0.11 mm). It is likely that the fibers, originated from the fisheries, recreational boating, laundry, domestic wastewater, and other human activities, which is also widespread and abundant (found in 58.58% of the fish studied). Polyethylene (PE) and polypropylene (PP) were identified as the most abundant polymers ingested by the fishes. There was no significant difference (p < 0.05) between the presence of microplastic in fish depending on their habitat. The prevalence of MPs is relatively low compared to those in other regions, despite the massive industrialization of the Saudi Arabian Gulf.


Clinical significance of skull base fracture in patients after traumatic brain injury.
About 4% of all head injuries include skull base fractures. Most of these fractures (90%) are secondary to closed head trauma; the remainder are due to penetrating trauma. We reviewed the records from January 2006 through December 2008 of all patients older than 18 years of age who arrived at Soroka Medical Center in Be'er-Sheva, Israel, with skull base fractures following a traumatic brain injury (TBI). We identified 107 patients with a mean age of 42 years at the time of TBI. Glasgow Coma score on arrival predicted the clinical outcome. We observed temporal fractures in 30% of these patients, occipital fractures in 20%, pyramidal fractures in 19%, anterior skull base fractures in 17%, and multiple fractures in 14%. Cerebrospinal fluid (CSF) leak was observed in 16 patients (15%). Of the patients experiencing CSF leaks, otorrhea occurred in 10 (62%) and rhinorrhea occurred in six (37%). Three patients required surgical intervention to repair the leak. Meningitis occurred in four patients with clinically evident CSF leak. Multiple skull base fractures are associated with poor neurological outcome. The low rate of meningitis in this patient sample implies that there is no indication to administer prophylactic antibiotics to patients with skull base fractures.


A dielectrophoretic method of discrimination between normal oral epithelium, and oral and oropharyngeal cancer in a clinical setting.
Despite the accessibility of the oral cavity to clinical examination, delays in diagnosis of oral and oropharyngeal carcinoma (OOPC) are observed in a large majority of patients, with negative impact on prognosis. Diagnostic aids might help detection and improve early diagnosis, but there remains little robust evidence supporting the use of any particular diagnostic technology at the moment. The aim of the present feasibility first-in-human study was to evaluate the preliminary diagnostic validity of a novel technology platform based on dielectrophoresis (DEP). DEP does not require labeling with antibodies or stains and it is an ideal tool for rapid analysis of cell properties. Cells from OOPC/dysplasia tissue and healthy oral mucosa were collected from 57 study participants via minimally-invasive brush biopsies and tested with a prototype DEP platform using median membrane midpoint frequency as main analysis parameter. Results indicate that the current DEP platform can discriminate between brush biopsy samples from cancerous and healthy oral tissue with a diagnostic sensitivity of 81.6% and a specificity of 81.0%. The present ex vivo results support the potential application of DEP testing for identification of OOPC. This result indicates that DEP has the potential to be developed into a low-cost, rapid platform as an assistive tool for the early identification of oral cancer in primary care; given the rapid, minimally-invasive and non-expensive nature of the test, dielectric characterization represents a promising platform for cost-effective early cancer detection.


Specific features in linear and spatial organizations of pericentromeric heterochromatin regions in polytene chromosomes of the closely related species Drosophila virilis and D. kanekoi (Diptera: Drosophilidae).
Heterochromatin plays an important role in the spatial arrangement and evolution of the eukaryotic genetic apparatus. The closely related species Drosophila virilis (phyla virilis) and D. kanekoi (phyla montana) differ in the amount of heterochromatin along the chromosomes as well as by the presence of the metacentric chromosome 2, which emerged as a result of a pericentric inversion during speciation, in the D. kanekoi karyotype. The purpose of this study was to establish if chromosome rearrangements have any influence on the linear redistribution of centromeric heterochromatin in polytene chromosomes and the spatial organization of chromosomes in the nuclei of nurse cell. We have microdissected the chromocenter of D. virilis salivary gland polytene chromosomes; obtained a DNA library of this region (DvirIII); and hybridized (FISH) DvirIII to the salivary gland and nurse cell polytene chromosomes of D. virilis and D. kanekoi. We demonstrated that DvirIII localizes to the pericentromeric heterochromatin regions of all chromosomes and peritelomeric region of chromosome 5 in both species. Unlike D. virilis, the DvirIII signal in D. kanekoi chromosomes is detectable in the telomeric region of chromosome 2. We have also conducted a 3D FISH of DvirIII probe to the D. virilis and D. kanekoi nurse cell chromosomes. In particular, the DvirIII signal in D. virilis was observed in the local chromocenter at one pole of the nucleus, while the signal belonging to the telomeric region of chromosome 5 was detectable at the other pole. In contrast, in D. kanekoi there exist two separate DvirIII-positive regions. One of these regions belongs to the pericentromeric region of chromosome 2 and the other, to pericentromeric regions of the remaining chromosomes. These results suggest that chromosome rearrangements play an important role in the redistribution of heterochromatin DNA sequences in the genome, representing a speciation mechanism, which, in general, could also affect the chromosome orientation in the 3D nuclear space.


[Vectors of malaria: biology, diversity, prevention, and individual protection].
Only the Anopheles mosquitoes are implicated in the transmission of malaria. Among the numerous species of anopheles, around fifty are currently involved in the transmission. 20 are responsible for most of the transmission in the world. The diversity of behavior between species and in a single species of anopheles as well as climatic and geographical conditions along with the action of man on the environment condition the man vector contact level and the various epidemiological aspects of malaria. The anopheles are primarily rural mosquitoes and are less likely to be found in city surroundings in theory. But actually, the adaptation of some species to urban surroundings and the common habit of market gardening in big cities or in the suburbs is responsible for the de persistence of Anopheles populations in town. Except for South-East Asia, urban malaria has become a reality. The transmission risk of malaria is heterogeneous and varies with time. There is a great variation of risk within a same country, a same zone, and even within a few kilometers. The transmission varies in time according to seasons but also according to years and to the level of climatic events. For the traveler, prevention at any time relies on the strict application of individual protection, as well in rural than in urban surroundings.


A patchy horizontal organization of the somatosensory activation of the rat cerebellum demonstrated by functional MRI.
Blood oxygenation level dependent contrast (BOLD) functional MRI (fMRI) responses, in a 7-T magnet, were observed in the cerebellum of alpha-chloralose anaesthetized rats in response to innocuous electrical stimulation of a forepaw or hindpaw. The responses were imaged in both coronal and sagittal slices which allowed for a clear delineation and localization of the observed activations. We demonstrate the validity of our fMRI protocol by imaging the responses in somatosensory cortex to the same stimuli and by showing reproducibility of the cerebellar responses. Widespread bilateral activations were found with mainly a patchy and mediolateral band organization, more pronounced ipsilaterally. Possible parasagittal bands were observed only in contralateral lobule VI. There was no overlap between the cerebellar activations caused by forepaw and hindpaw stimuli. The overall horizontal organization of these responses was quite remarkable. For both stimulation paradigms most of the activation patches were positioned in either a rostral or caudal broad plane running anteroposteriorly through both anterior and posterior cerebellum. The rostral planes were completely separated, with the forepaw activation closer to the surface, while the caudal plane was common to both stimulation protocols. We relate our findings to the known projection patterns of spinocerebellar and cuneocerebellar mossy fibres, and to human fMRI studies.


Density of Demodex folliculorum in haematological malignancies.
We aimed to investigate the incidence and density of Demodex folliculorum in adults with leukaemia or lymphoma. Fifty patients with haematological malignancy and 50 healthy controls were studied. Patients had been diagnosed with acute lymphocytic leukaemia (12%), acute myelocytic leukaemia (32%), chronic lymphocytic leukaemia (4%), chronic myelocytic leukaemia (10%), Hodgkin's lymphoma (4%) or non-Hodgkin's lymphoma (38%). Standardized skin surface biopsies were taken and > or = 5 living parasites/cm2 of skin was defined as an infestation. The difference in infestation rates between patients and controls was statistically significant. The highest incidences of D. folliculorum were found in patients with acute myelocytic leukaemia (10%), non-Hodgkin's lymphoma (6%), acute lymphocytic leukaemia (4%), chronic lymphocytic leukaemia (4%) and chronic myelocytic leukaemia (4%). Demodicidosis should be included in the differential diagnosis of facial eruptions in patients with haematological malignancies who are receiving chemotherapy, and a standardized skin surface biopsy should be performed.


Integrating genomics into the care of people with palliative needs: A global scoping review of policy recommendations.
Genomics has growing relevance to palliative care, where testing largely benefits relatives. Integration of genomics into the care of patients with palliative care needs has not received the critical attention it requires, and health professionals report a lack of policy guidance to support them to overcome practice barriers. To identify policy recommendations related to: (1) integrating genomics into the care of patients with palliative care needs and their families, and (2) care of the family unit, we performed a scoping review of palliative care and genomic policies. Two of 78 policies recommended integrating genomics into palliative care. Six palliative care policies mentioned genomics in background information but were without relevant recommendations. No genomics policies mentioned palliative care in the background information. Across all policies, guidance related to "Delivering Family-Centred Care" was the most frequent recommendation related to care of the family unit, (n=62/78, 79.5%). We identified a policy gap related to integrating genomics into palliative care. Without policy guidance, health services are less likely to commit funding towards supporting health professionals, reducing the personal and clinical benefits of genomics to patients and relatives. Framing genomic information as family-centred care enables policy makers to communicate the value of genomics to palliative care that will resonate with genomic and palliative care stakeholders. These findings increase awareness among policy makers of the benefits of genomic information to patients with palliative care needs and their families and call for incorporation of appropriate recommendations into palliative care and genomic policy.


Three-dimensional nature of retinal nerve fiber layer defects.
To demonstrate the 3-dimensional nature of wedge-shaped retinal nerve fiber layer (RNFL) losses. To study the impact of training glaucoma fellows in this identification technique by evaluating their rate of RNFL loss detection on stereo disc photographs. Wedge-shaped RNFL defects were identified in stereo disc photographs of early-glaucoma patients. The 3-dimensional nature of RNFL defects and overlying retinal blood vessel contour changes were identified. Four glaucoma fellows were given stereophotographs to identify the presence or absence of RNFL defects. After training in identification of RNFL defects by noting their 3-dimensional nature and overlying blood vessel contour changes, the same set of photographs were reevaluated by the fellows. We determined whether there was a difference between the before and after assessments in the probability of a correct response for each of the fellows. Loss of retinal thickness in the form of grooves and the resulting 3-dimensional nature of the RNFL defects were visualized on stereoscopic examination. Overlying retinal blood vessels coursed into and out of the RNFL defects. Three case examples of such wedge-shaped RNFL defects are presented. For each fellow, the proportion of RNFL defects correctly identified after training was greater than the proportion before training (P<0.001). Identifying the 3-dimensional nature of wedge-shaped RNFL defects may improve rate of detection of RNFL defects during clinical examination.


[Cranberries for prevention of recurrent urinary tract infections].
Cranberries have been used for prevention and treatment of urinary tract infections for decades. The berries contain proanthocyanidins that may reduce the susceptibility to infection by preventing bacteria from attaching to uroepithelial cells. Several clinical trials have been published during recent years. This article reviews documentation of cranberries on clinical effect, adverse events, drug interactions and use during pregnancy and lactation. Clinical effects of cranberries have been assessed based on the Cochrane review from January 2007 and literature on clinical trials retrieved from a systematic search of PubMed and Embase (from 1 January 2007 to 29 October 2008) with the search terms "cranberry", "Vaccinium macrocarpon", "Vaccinium oxycoccus". Some evidence exists on cranberries' preventive effect on recurrent symptomatic urinary tract infections in women. The evidence is inconclusive for children, men and older people (both men and women). Studies of people with neuropathic bladder are contradictory. Most of the clinical trials published have several flaws and have not used standardised products. More evidence is needed to determine the optimum dosage, method of administration and the minimum length of treatment. Cranberries should not be used during pregnancy and lactation due to lack of safety data. Further, properly designed studies with standardised products and relevant outcomes are needed.


Mesothelial reaction in longstanding Crohn's ileitis simulating papillary mesothelioma.
Intestinal and extraintestinal complications of Crohn's disease are well documented. Changes in the connective tissue within the intestinal wall and surrounding tissue including mesenteric fat are characteristically seen in resected and autopsy specimens. A rare and unusually florid mesothelial reaction in the surrounding small bowel serosa of a patient with a 2-year history of Crohn's ileitis is described. The peritoneal surface of the ileal resection specimen displayed exuberant tubulo-papillary formations of the mesothelium, with superficial invasion of the underlying stroma. The case demonstrates the well-recognised difficult differential diagnosis between a benign mesothelial proliferation and malignant mesothelioma in a novel clinical setting, and the diversity of the extramural manifestations of Crohn's disease.


Agreement between patient reports of cardiovascular disease and patient medical records.
To determine how well patient-reported cardiovascular disease (CVD) and CVD risk factor information agrees with medical record information. Information from Patient/Family History (PFH) questionnaires completed between 1996 and 1999 by residents of Olmsted County, Minnesota, aged 20 years and older was compared with information available through the Mayo Clinic medical diagnostic index. Positive and negative agreement values were calculated by comparing agreement between the 2 data sources. Also, with the Mayo Medical Index serving as the criterion standard, sensitivity, specificity, and positive and negative predictive values of questionnaire information were calculated overall and by subgroups of sex, age, and years of education. Questionnaire responses were retrieved for 26,162 patients. Positive agreement values ranged from 31% for report of a medical problem or surgery related to arteries to the head, arms, or legs or the aorta to 78% for high blood pressure. Negative agreement values ranged from 90% for high cholesterol to 98% for medical problem or surgery related to arteries to the head, arms, or legs or the aorta. Sensitivity of questionnaire information ranged from 37% to 73%, whereas positive predictive values ranged from 27% to 86%. Positive agreement, sensitivity, and positive predictive values tended to increase with increasing age of the patient. Specificity and negative predictive values were 87% or greater, and negative agreement, specificity, and negative predictive values decreased with increasing age. Positive patient reports of CVD conditions and risk factors are relatively inaccurate. However, negative self-reports of these conditions are unlikely to be noted in the medical record. Further development of the PFH questionnaire is necessary to ensure accurate patient reporting of CVD data.


Effect of bacopa monniera on cold stress induced neurodegeneration in hippocampus of wistar rats: a histomorphometric study.
Bacopa monniera/ Brahmi,is used over centuries in Ayurvedic medicine for memory development, learning, concentration and other mental illnesses such as nervousness and poor cognition. The present study aims to evaluate the effect of Bacopa monniera (Brahmi, BM) on cold stress induced histological changes in hippocampus of Wistar rats. Total 24 male rats divided into four groups were used (n=6) for this study. Group I was control in which rats were kept under ideal laboratory conditions, Group II was given 40 mg/kg of BM extract, Group III was cold water swim stress in which rats were forced to swim in the cold water maintained at 18±2(o)C till it started to sink for a period of one month and Group IV in which cold water swim stress given for a month followed by oral administration of BM extracts 40mg/kg treatment for a month. The whole study was carried out for a period of 60 d. The animals were sacrificed next day and their brains dissected out for histomorphometric analysis. The diameter, packing density and total number of neurons were calculated from stained histological section by using micrometry in the CA-1 region of the hippocampus. The analysis and plotting of graphs were carried out using Sigma Plot 12 (Systat Software Inc., USA). Values are expressed as Mean ± SEM (n = 6). One way analysis of variance followed by Student-Newman-Keul's multiple comparisons test was used for the comparison of means. A probability of 0.05 and less was taken as statistically significant. The results showed that there is no significant difference in the diameter of the cells between the groups but total number of the cells in Group II was statistically significant when compared with the others groups. Student-Newman-Keuls method showed that Group II and Group IV are statistically significant when compared to Group III (p<0.05). RESULTS indicates that when BM extracts administered orally produce neuroprotective effect in cold stress induced hippocampal neurodegeneration of rats. Hence, the herb BM can possibly be used as an adjuvant to improve memory to combat stress in our day to day life.


Resistance to the aminoglycoside antibiotic neamine in Escherichia coli. A new mutant whose NeaR phenotype results from the cumulative effects of two distinct mutations.
A spontaneous mutant of Escherichia coli (strain AB2847), selected for resistance to the aminoglycoside antibiotic neamine, shows severe restriction of amber suppressors in vivo. Ribosomes isolated from the mutant exhibit only low misreading in vitro in the presence of the antibiotic. Genetic and biochemical analyses indicate that the neamine-resistant phenotype is the result of two distinct mutations. The first, res3128, appears to affect the gene (strA) coding for the ribosomal protein S12. Although it leads to a restrictive phenotype it does not, however, confer resistance to streptomycin. The second mutation, X3128, is located between the sirA and AROB loci and is lethal when segregated from the res3128 mutation. It may affect the ribosome at the level of a post-translational modification.


Fatigue in out-patients with inflammatory bowel disease: Prevalence and predictive factors.
Fatigue is a common and bothersome symptom in inflammatory bowel disease (IBD) patients. The study was aimed to determine the relationship of biological and psychological factors with IBD-related fatigue. Consecutive clinically inactive IBD outpatients receiving immunosuppressants or biological drugs were enrolled between January and December 2013. Patients completed a Fatigue score (FACIT-F), various psychological, quality of life (IBDQ-9), and IBD activity scores. Biological parameters were assessed, including levels of interleukins (IL-5, IL-8 and IL-12) and micronutrients. We prospectively recruited 202 patients (28% ulcerative colitis and 72% Crohn's disease) for the study. Fatigue measured by FACIT-F score was prevalent in the studied population (54%, 96/177) and higher than in the general population. In the univariate analysis no relation was found between IL levels or micronutrient deficiencies and fatigue. Fatigue was significantly related to female sex, Crohn's disease, joint disorders, body mass index (BMI), psychological tests, thiopurine use, and anti-TNF treatment. All these variables were included in the multivariate analysis. Female sex (OR: 4.8), high BMI (OR:1.2) and higher depression rates (OR:1.2) were predictors of increased fatigue. High IBDQ-9 score (OR: 0.82) was significantly related to lower degrees of fatigue. Fatigue was prevalent in quiescent IBD patients with moderate-to-severe disease. It was associated with high levels of depression, low quality of life, and female sex. No association was found with the other biological and psychological factors evaluated.


The roles of endoglin gene in cerebrovascular diseases.
Endoglin (ENG, also known as CD105) is a transforming growth factor β (TGFβ) associated receptor and is required for both vasculogenesis and angiogenesis. Angiogenesis is important in the development of cerebral vasculature and in the pathogenesis of cerebral vascular diseases. ENG is an essential component of the endothelial nitric oxide synthase activation complex. Animal studies showed that ENG deficiency impairs stroke recovery. ENG deficiency also impairs the regulation of vascular tone, which contributes to the pathogenesis of brain arteriovenous malformation (bAVM) and vasospasm. In human, functional haploinsufficiency of ENG gene causes type I hereditary hemorrhagic telangiectasia (HHT1), an autosomal dominant disorder. Compared to normal population, HHT1 patients have a higher prevalence of AVM in multiple organs including the brain. Vessels in bAVM are fragile and tend to rupture, causing hemorrhagic stroke. High prevalence of pulmonary AVM in HHT1 patients are associated with a higher incidence of paradoxical embolism in the cerebral circulation causing ischemic brain injury. Therefore, HHT1 patients are at risk for both hemorrhagic and ischemic stroke. This review summarizes the possible mechanism of ENG in the pathogenesis of cerebrovascular diseases in experimental animal models and in patients.


Big Data and Artificial Intelligence Modeling for Drug Discovery.
Due to the massive data sets available for drug candidates, modern drug discovery has advanced to the big data era. Central to this shift is the development of artificial intelligence approaches to implementing innovative modeling based on the dynamic, heterogeneous, and large nature of drug data sets. As a result, recently developed artificial intelligence approaches such as deep learning and relevant modeling studies provide new solutions to efficacy and safety evaluations of drug candidates based on big data modeling and analysis. The resulting models provided deep insights into the continuum from chemical structure to in vitro, in vivo, and clinical outcomes. The relevant novel data mining, curation, and management techniques provided critical support to recent modeling studies. In summary, the new advancement of artificial intelligence in the big data era has paved the road to future rational drug development and optimization, which will have a significant impact on drug discovery procedures and, eventually, public health.


Cell signaling model for arterial mechanobiology.
Arterial growth and remodeling at the tissue level is driven by mechanobiological processes at cellular and sub-cellular levels. Although it is widely accepted that cells seek to promote tissue homeostasis in response to biochemical and biomechanical cues-such as increased wall stress in hypertension-the ways by which these cues translate into tissue maintenance, adaptation, or maladaptation are far from understood. In this paper, we present a logic-based computational model for cell signaling within the arterial wall, aiming to predict changes in extracellular matrix turnover and cell phenotype in response to pressure-induced wall stress, flow-induced wall shear stress, and exogenous sources of angiotensin II, with particular interest in mouse models of hypertension. We simulate a number of experiments from the literature at both the cell and tissue level, involving single or combined inputs, and achieve high qualitative agreement in most cases. Additionally, we demonstrate the utility of this modeling approach for simulating alterations (in this case knockdowns) of individual nodes within the signaling network. Continued modeling of cellular signaling will enable improved mechanistic understanding of arterial growth and remodeling in health and disease, and will be crucial when considering potential pharmacological interventions.


Use of magnetic techniques for the isolation of cells.
Magnetic separation is an emerging technology using magnetism, sometimes in combination with conventional separation or identification methods, to purify cells, cell organelles and biologically active compounds (nucleic acids, proteins, xenobiotics) directly from crude samples. Several magnetic separation procedures have been developed to isolate target cells specifically. The purpose of this short review is to summarize various methodologies, strategies and materials which can be employed for the selection and separation of target cells with the help of magnetic field and thus to help the novices in this field to be able to orient themselves in vast amount of literature available. Immunomagnetic separations employing specific antibodies to label the target cells represent the most often used approach and are discussed in detail.


[Symptomatic parathyroid cysts. Report of one case].
Parathyroid cysts are unusual and do not have specific clinical manifestations or ultrasonographic findings. Therefore, they are usually confused with thyroid nodules. We report a 43 years old male, with normal thyroid function and normal calcium serum levels, that presented a nodule in the lower right third of the neck. Ultrasonography and CAT scan showed a well delimited 6 x 4.5 cm ovoid cyst that compressed and displaced the trachea and esophagus. A fine needle aspiration was done on three occasions, extracting 18, 40 and 60 ml of liquid. As the cyst recurred and symptoms intensified, the patient was operated removing the cyst and the right thyroid lobe. Pathological study disclosed a parathyroid cyst.


Pseudoaminopterin syndrome: clinical report with new characteristics.
Fetuses exposed to aminopterin during the 8th-9th week of development may show aminopterin embryophathy (AE). Surviving children have a specific phenotype that includes unusual face, skull, and skeletal abnormalities. Fraser et al. [Fraser et al. (1987); Clin Genet 32:28-34] described two children with multiple malformations characteristic of the aminopterin syndrome but without history of exposure to aminopterin in the mothers and suggested that this represents a new syndrome, the aminopterin syndrome-like sine aminopterin (ASSA) syndrome. Here we describe a 9-year-old girl, born to unaffected first cousin parents. She has short stature, microcephaly, broad forehead with high hair implantation; sparse and fine hair, areas of alopecia; arched eyebrows with upturned hair, synophris; ocular hypertelorism, epicanthal folds, palpebral ptosis; oligodontia; low-set and small ears with hypoplasia of antihelices; brachydactyly, clinodactyly of both 4th and 5th fingers; hypoplasia of the 4th metacarpal and clinodactyly of the 4th and 5th toes; overlap of the second over the third toe; bilateral hip luxation; patent foramen ovale; left posterior diaphragmatic hernia, absence of spleen and horseshoe kidney. She, her mother and her brother have a karyotype of 46,XX, with an inv(9)(p12q13) polymorphism. Although this patient has some characteristics did not described before in patients with ASSA such as, palpebral ptosis, oligodontia, left posterior diaphragmatic hernia, absence of spleen, and horseshoe kidney, her phenotype strongly suggest she has the pseudoaminopterin syndrome. However, we do not exclude the possibility that this is a different condition not described previously.


Learning Social Media Content Optimization: How Can SMEs Draw the Users' Attention on Official WeChat Accounts?
Application of artificial intelligence is accelerating the digital transformation of enterprises, and digital content optimization is crucial to take the users' attention in social media usage. The purpose of this work is to demonstrate how social media content reaches and impresses more users. Using a sample of 345 articles released by Chinese small and medium-sized enterprises (SMEs) on their official WeChat accounts, we employ the self-determination theory to analyze the effects of content optimization strategies on social media visibility. It is found that articles with enterprise-related information optimized for content related to users' psychological needs (heart-based content optimization, mind-based content optimization, and knowledge-based content optimization) achieved higher visibility than that of sheer enterprise-related information, whereas the enterprise-related information embedded with material incentive (benefits-based content optimization) brings lower visibility. The results confirm the positive effect of psychological needs on the diffusion of enterprise-related information, and provide guidance for SMEs to apply artificial intelligence technology to social media practice.


Influence of processing on protein quality.
In the first part the reactions and interactions of protein with macroconstituents of our food during processing are exposed from the chemical point of view. The reactions involving only protein (formation of isopeptides, of lysinoalanine, racemization) and the interactions with carbohydrates (Maillard reaction), oxidized lipids and polyphenols are briefly presented. Emphasis is put on the Maillard reaction since it is the most frequent reaction occurring during food processing and storage. The key compound rendering lysine unavailable in processed and stored foodstuffs in N epsilon-fructoselysine (FL). Its oxidative degradation product, N epsilon-carboxymethyllysine (CML) is found in variable but significant amounts in heat processed proteins. An interesting newer finding is that tryptophan can participate in a Maillard reaction with its indole-NH-group. In the second part an overview is given on the impact these reactions have on the two components of protein nutritive value, namely digestibility and biological value. Again, most examples will be related to the Maillard reaction. Protein digestibility may be reduced by the modification of the protein molecule (blocking of active amino acid side-chains, establishment of crosslinks) or by the formation of compounds that inhibit digestive enzymes. (Inhibition of aminopeptidase by an advanced Maillard derivative of lysine). Biological value may be diminished by the loss of essential amino acids and/or their reduced specific availability. Ion-exchange chromatography of the protein hydrolyzate is the method of choice to determine amino acid losses. It also provides some clues for the type of processing damage by the presence of unusual amino acids in the chromatogramme (e.g. furosine, lysinoalanine). Global amino acid bioavailability is defined. It is of a complex nature and can only be truely determined in a bioassay in the animal. Specific availability of an amino acid is linked to particular structural features. Thus, specific lysine availability is determined by the presence of a free or "reactive" epsilon-amino group. This is the basis for the analytical methods for available lysine. In the third part, the practical application of this knowledge to processed foods is shown using milk and vegetable protein as examples. Figures for the reduction in available lysine (blocked lysine) in different milk products processed according to conventional procedures are given and discussed. More subtile effects of milk processing on milk digestibility and stomach emptying are mentioned. The effects on protein nutritional value of extrusion-cooking of legume seeds and cereal flours are, then, presented.(ABSTRACT TRUNCATED AT 250 WORDS)


NF-kappaB-mediated induction of mdr1b expression by insulin in rat hepatoma cells.
The expression of P-glycoproteins encoded by the mdr gene family is associated with the emergence of multidrug resistance phenotype in animal cells. However, the mechanisms controlling the expression of these genes have not been well elucidated. Here, we report that the expression of rat mdr1b gene in cultured H-4-II-E hepatoma cells can be induced by insulin. Transient transfection assays using reporter gene constructs containing various 5' mdr1b sequences showed that the sequence located between base pairs -243 and -163 is important for insulin's induction of mdr1b promoter activity. Further analyses revealed that a NF-kappaB-binding site (located between base pairs -167 and -158) is required for insulin-induced promoter activity. Gel mobility shift assay demonstrated that insulin stimulates the binding of nuclear p50/p65 subunits to the mdr1b NF-kappaB sequence. Cotransfection of plasmids expressing either the p50/p65 NF-kappaB subunits or Raf-1 kinase or both resulted in increased expression of the gene containing wild-type but not NF-kappaB site-mutated mdr1b promoter. Finally, expression of either the antisense p65 subunit of NF-kappaB or dominant negative Raf-1 kinase blocked insulin's induction of the mdr1b promoter activity. Taken together, our results suggest that the insulin-induced mdr1b expression is mediated by transcription factor NF-kappaB via the Raf-1 kinase signaling pathway.


Dual-Task Performance: Influence of Frailty, Level of Physical Activity, and Cognition.
Cognition and level of physical activity have been associated with frailty syndrome. The development of tools that assess deficits related to physical and cognitive frailties simultaneously are of common interest. However, little is known about how much these aspects influence the performance of dual-task tests. Our aims were (a) to verify the influence of frailty syndrome and objectively measured physical activity and cognition on the Timed Up and Go (TUG) test and Timed Up and Go associated with dual-task (TUG-DT) performances; and (b) to compare TUG and TUG-DT performances between older adults who develop frailty syndrome. Sixty-four community-dwelling older adults were divided into frail, prefrail, and nonfrail groups, according to frailty phenotype. Assessments included anamnesis, screening of frailty syndrome, cognitive assessment (Addenbrooke's Cognitive Examination), placement of a triaxial accelerometer to assess level of physical activity, and TUG and TUG-DT (TUG associated with a motor-cognitive task of calling a phone number) performances. After 7 days, the accelerometer was removed. A multiple linear regression was applied to identify which independent variables could explain performances in the TUG and TUG-DT. Subsequently, the analysis of covariance test, adjusted for age, cognition, and level of physical activity covariates, was used to compare test performances. There were no differences in cognition between groups. Significant differences in the level of physical activity were found in the frail group. Compared with the frail group, the nonfrail group required less time and fewer steps to complete the TUG. Regarding the TUG-DT, cognition and age influenced the time spent and number of steps, respectively; however, no differences were found between groups. Frail older adults presented worse performance in the TUG when compared with nonfrail older adults. The dual-task test does not differentiate older adults with frailty syndrome, regardless of cognitive performance.


Vaccination with tetanus, diphtheria, and acellular pertussis vaccine of pregnant women enrolled in Medicaid--Michigan, 2011-2013.
In October 2011, the Advisory Committee on Immunization Practices (ACIP) first recommended the routine administration of a tetanus, diphtheria, and acellular pertussis vaccine (Tdap) during pregnancy as a strategy to protect infants from pertussis (also known as whooping cough). This recommendation applied to women previously unvaccinated with Tdap and specified the optimal vaccination time as late second or third trimester (after 20 weeks' gestation). By vaccinating pregnant women, infants, who are at highest risk for mortality and morbidity from pertussis, gain passive immunity from maternal antibodies transferred to them in utero. Since this recommendation was made, little has been published on the percentage of women receiving Tdap during pregnancy. In Michigan, Medicaid pays for costs of pregnancy for approximately 40% of births. Infants enrolled in Medicaid are a particularly vulnerable population; in Michigan, their all-cause mortality is higher than that of privately insured infants. To assess vaccination coverage among pregnant women enrolled in a publicly funded insurance program in Michigan, Medicaid administrative claims data and statewide immunization information system data for mothers of infants born during November 2011-February 2013 were analyzed. This report describes the results of that analysis, which indicated that only 14.3% of these women received Tdap during pregnancy, with rates highest (17.6%) among non-Hispanic, non-Arab whites and lowest (6.8%) among Arab women. Vaccination was related to maternal age and gestational age at birth, but not to adequacy of prenatal care. In 2013, recognizing the importance of Tdap for every pregnancy, ACIP revised its guidelines to include a Tdap dose during every pregnancy. Ensuring that all infants receive the protection against pertussis afforded by maternal vaccination will require enhanced efforts to vaccinate pregnant women.


Sex- and age-dependent differences in nicotine susceptibility evoked by developmental exposure to tobacco smoke and/or ethanol in mice.
Either tobacco smoking or alcohol consumption during pregnancy sex-selectively increases susceptibility to drugs of abuse later in life. Considering that pregnant smoking women are frequently intermittent consumers of alcoholic beverages, here, we investigated whether a short-term ethanol exposure restricted to the brain growth spurt period when combined with chronic developmental exposure to tobacco smoke aggravates susceptibility to nicotine in adolescent and adult mice. Swiss male and female mice were exposed to tobacco smoke (SMK; research cigarettes 3R4F, whole-body exposure, 8 h/daily) or ambient air during the gestational period and until the tenth postnatal day (PN). Ethanol (ETOH, 2 g/Kg, 25%, i.p.) or saline was injected in the pups every other day from PN2 to PN10. There were no significant differences in cotinine (nicotine metabolite) and ethanol serum levels among SMK, ETOH and SMK + ETOH groups. During adolescence (PN30) and adulthood (PN90), nicotine (NIC, 0.5 mg/Kg) susceptibility was evaluated in the conditioned place preference and open field tests. NIC impact was more evident in females: SMK, ETOH and SMK + ETOH adolescent females were equally more susceptible to nicotine-induced place preference than control animals. At adulthood, SMK and SMK + ETOH adult females exhibited a nicotine-evoked hyperlocomotor profile in the open field, with a stronger effect in the SMK + ETOH group. Our results indicate that ethanol exposure during the brain growth spurt, when combined to developmental exposure to tobacco smoke, increases nicotine susceptibility with stronger effects in adult females. This result represents a worsened outcome from the early developmental dual exposure and may predispose nicotine use/abuse later in life.


Structural Basis of DNMT1 and DNMT3A-Mediated DNA Methylation.
DNA methylation, one of the major epigenetic mechanisms, plays critical roles in regulating gene expression, genomic stability and cell lineage commitment. The establishment and maintenance of DNA methylation in mammals is achieved by two groups of DNA methyltransferases (DNMTs): DNMT3A and DNMT3B, which are responsible for installing DNA methylation patterns during gametogenesis and early embryogenesis, and DNMT1, which is essential for propagating DNA methylation patterns during replication. Both groups of DNMTs are multi-domain proteins, containing a large N-terminal regulatory region in addition to the C-terminal methyltransferase domain. Recent structure-function investigations of the individual domains or large fragments of DNMT1 and DNMT3A have revealed the molecular basis for their substrate recognition and specificity, intramolecular domain-domain interactions, as well as their crosstalk with other epigenetic mechanisms. These studies highlight a multifaceted regulation for both DNMT1 and DNMT3A/3B, which is essential for the precise establishment and maintenance of lineage-specific DNA methylation patterns in cells. This review summarizes current understanding of the structure and mechanism of DNMT1 and DNMT3A-mediated DNA methylation, with emphasis on the functional cooperation between the methyltransferase and regulatory domains.


Sentinel lymph node dissection in breast cancer.
During the last years, the efficacy and reliability of the sentinel lymph node biopsy (snb) as a minimal invasive diagnostic procedure for the nodal status has been intensively evaluated. After the widespread clinical use in the staging of melanoma patients the snb is currently introduced in the clinical management of breast cancer patients. We present our experience with this method during 3, 5 years and discuss its potential and pitfalls. From 11/95 to 3/99 we performed sentinel node detection in 146 patients with breast cancer stage I to III, consisting of 127 patients with pT1/2-tumors and 19 patients with pT3/4-tumors. We used the radionuclid method including preoperative lymphoscintigraphy and intraoperative gamma-probe detection. The detection rate varied with the tumor size between 94% for tumors with a diameter < 1 cm, 85% (1-3 cm), 70% (3-5 cm) and 63% (> 5 cm). The accuracy of the snb in the prediction of the nodal status changed also with the tumor diameter between 100% for very small tumors (< 1 cm), 97% (1-3 cm), 88% (3-5 cm) and 67% (> 5 cm). In the subgroup of patients restricted to T1-2-tumors (n = 106). 57 patients (53%) showed true negative snb. 38 patients (36%) revealed tumor cells in the H&E-staining and an additional 7 patients (7%) solely in the immunohistochemical staining. 4 (4%) of these patients, all of them from the first half of the study period, underwent false-negative snb, 3 of them showing lymphangiosis carcinomatosa. The presented results show, that snb using the radionuclid method is a reliable method for the evaluation of the nodal status in early breast cancer patients with a tumor size up to ca. 3 cm. Therefore the sn procedure should be restricted to small tumors with clinically uninvolved axillary nodes or patients with a ductal carcinoma in situ (DCIS) to rule out invasiveness.


Comparison of the results of Cox proportional hazards model and parametric models in the study of length of stay in a tertiary teaching hospital in Tehran, Iran.
Survival analysis is a set of methods used for analysis of the data which exist until the occurrence of an event. This study aimed to compare the results of the use of the semi-parametric Cox model with parametric models to determine the factors influencing the length of stay of patients in the inpatient units of Women Hospital in Tehran, Iran. In this historical cohort study all 3421 charts of the patients admitted to Obstetrics, Surgery and Oncology units in 2008 were reviewed and the required patient data such as medical insurance coverage types, admission months, days and times, inpatient units, final diagnoses, the number of diagnostic tests, admission types were collected. The patient length of stay in hospital 'leading to recovery' was considered as a survival variable. To compare the semi-parametric Cox model and parametric (including exponential, Weibull, Gompertz, log-normal, log-logistic and gamma) models and find the best model fitted to studied data, Akaike's Information Criterion (AIC) and Cox-Snell residual were used. P<0.05 was considered as statistically significant. AIC and Cox-Snell residual graph showed that the gamma model had the lowest AIC (4288.598) and the closest graph to the bisector. The results of the gamma model showed that factors affecting the patient length of stay were admission day, inpatient unit, related physician specialty, emergent admission, final diagnosis and the number of laboratory tests, radiographies and sonographies (P<0.05). The results showed that the gamma model provided a better fit to the studied data than the Cox proportional hazards model. Therefore, it is better for researchers of healthcare field to consider this model in their researches about the patient length of stay (LOS) if the assumption of proportional hazards is not fulfilled.


Nutritional support for rabbits using the percutaneously placed gastrostomy tube: a preliminary study.
A feeding-tube gastrostomy technique used in dogs and cats has been adapted to the rabbit. A detailed description of the percutaneous, incisionless placement of a gastrostomy tube using a gastroscope is presented. Management of the feeding tube and the formulation of a liquid diet for rabbits also are described. The percutaneous endoscopical gastrostomy (PEG) tube was used successfully to administer enteral nutritional support to the rabbit.


The impact of service and hearing dogs on health-related quality of life and activity level: a Swedish longitudinal intervention study.
Individuals with severe disability often require personal assistance and help from informal caregivers, in addition to conventional health care. The utilization of assistance dogs may decrease the need for health and social care and increase the independence of these individuals. Service and hearing dogs are trained to assist specific individuals and can be specialized to meet individual needs. The aim of this study was to describe and explore potential consequences for health-related quality of life, well-being and activity level, of having a certified service or hearing dog. A longitudinal interventional study with a pre-post design was conducted. At inclusion, all participants in the study had a regular (untrained) companion dog. Data were collected before training of the dog started and three months after certification of the dog. Health-related quality of life was assessed with EQ-5D-3L, EQ-VAS and RAND-36. Well-being was measured with WHO-5 and self-esteem with the Rosenberg Self-Esteem Scale. In addition, questions were asked about physical activity and time spent away from home and on social activities. Subgroups were analyzed for physical service and diabetes alert dogs. Fifty-five owner-and-dog pairs completed the study (30 physical service dogs, 20 diabetes alert dogs, 2 epilepsy alert dogs, and 3 hearing dogs). Initially, study participants reported low health-related quality of life compared with the general population. At follow-up, health-related quality of life measured with the EQ-VAS, well-being and level of physical activity had improved significantly. In the subgroup analysis, physical service dog owners had lower health-related quality of life than diabetes alert dog owners. The improvement from baseline to follow-up measured with EQ-5D statistically differed between the subgroups. The target population for service and hearing dogs has an overall low health-related quality of life. Our study indicates that having a certified service or hearing dog may have positive impact on health-related quality of life, well-being and activity level. Service and hearing dogs are a potentially important "wagging tail aid" for this vulnerable population, able to alleviate strain, increase independence, and decrease the risk of social isolation. The trial was retrospectively registered in http://clinicaltrial.gov , NCT03270592. September, 2017.


Review of air pollution and health impacts in Malaysia.
In the early days of abundant resources and minimal development pressures, little attention was paid to growing environmental concerns in Malaysia. The haze episodes in Southeast Asia in 1983, 1984, 1991, 1994, and 1997 imposed threats to the environmental management of Malaysia and increased awareness of the environment. As a consequence, the government established Malaysian Air Quality Guidelines, the Air Pollution Index, and the Haze Action Plan to improve air quality. Air quality monitoring is part of the initial strategy in the pollution prevention program in Malaysia. Review of air pollution in Malaysia is based on the reports of the air quality monitoring in several large cities in Malaysia, which cover air pollutants such as Carbon monoxide (CO), Sulphur Dioxide (SO2), Nitrogen Dioxide (NO2), Ozone (O3), and Suspended Particulate Matter (SPM). The results of the monitoring indicate that Suspended Particulate Matter (SPM) and Nitrogen Dioxide (NO2) are the predominant pollutants. Other pollutants such as CO, O(x), SO2, and Pb are also observed in several big cities in Malaysia. The air pollution comes mainly from land transportation, industrial emissions, and open burning sources. Among them, land transportation contributes the most to air pollution. This paper reviews the results of the ambient air quality monitoring and studies related to air pollution and health impacts.


[Effects of soybean phospholipids on learning and memory ability and contents of lipids in mice's brain].
To study the effects of soybean phospholipids on learning and memory abilities and contents of protein and lipids in brain of mice. Mice were randomly divided into four groups: low dose (2.5 g/kg), middle dose(5.0 g/kg) and high dose (10.0 g/kg) of soybean Phospholipids in diet and control group (distilled water). The mice were fed with soybean phospholipids everyday while control groups were fed with distilled water for 30 days. After learning and memory abilities were measured, the mice were killed and contents of protein, fatty acids and phospholipids in brain of mice were determined. The learning and memory abilities of mice fed with middle and high dose of soybean Phospholipids were improved obviously(P < 0.05), while memory abilities of low dose's mice were stronger than that of control(P < 0.05). (2) The brain weight v.8 body weight of those in three doses' group was obviously increased, and the protein content in brain was significantly higher compared with control(P < 0.05). (3) The contents of linoleic acid(C18: 2), linolenic acid(C18: 3) and ratio of polyunsaturated fatty acids(PUFA) to total fatty acids (TFA) obviously increased (P < 0.05). In brain of high dose mice, there was obvious change in the content of linolenic acid(C18: 3) in middle's (P < 0.05). (4) The contents of phosphatidylcholine (PS) phosphatidylethanolamine (PE), Phosphatidylcholine (PC) and phospholipids (PL) obviously increase (P < 0.05), while ratio of SM to PC was decreased significantly in brain of high dose mice(P < 0.05). The contents of PS, PC and PL were increased obviously(P < 0.05). Soybean phospholipids may increase contents of protein, PUFA and PL in brain of mice and improve learning and memory abilities of mice effectively in a dose-response manner.


A study of antibody levels in alcoholic, depressive and schizophrenic patients.
A study was undertaken to compare IgG, IgA, IgM, IgE and IgD antibodies in adult alcoholic, depressive and schizophrenic patients with healthy, adult controls. Total IgG, -IgA, -IgM, -IgE, and -IgD and specific-IgE antibodies were assessed using 33 allergens: 12 inhalant and 21 foods. There was no significant difference observed in the total immunoglobulin results between the patients and controls. There were, however, significant differences between the groups for allergen specific-IgE with the depressive patients exhibiting the greatest number of positive test results. The depressives had an over-all t-test value of 10.080 (5% = 1.960), the alcoholics t = 6.800 and the schizophrenics t = 6.015. The most often positive allergens were those from the perennial/mold group, although the most frequently positive single allergen was egg white and 100% of the depressives were sensitive to it. The data in this investigation suggest that psychiatric patients with alcohol dependence, depression and schizophrenia be studied further so that information on a causal relationship between allergen specific-IgE antibodies and these mental disorders can be evaluated.


Magnetic resonance imaging of peripheral vascular disease. The state of the artery.
Peripheral vascular disease is a term often used to describe the manifestation of atherosclerosis below the bifurcation of the abdominal aorta. Peripheral atherosclerosis is a major cause of morbidity in the developed countries and 2% of adults in late middle age have intermittent claudication, which is severe enough in some patients to warrant hospital admission. The disease produces problems either by reducing blood flow or by the release of emboli from ulcerated plaques. The morphology and composition of arterial segments containing atheroma is of considerable importance. Plaques of different morphology have different effects on the arterial wall, such as the potential for thrombosis and the effect of arterial spasm. The lipid content may also affect the propensity for fissuring, ulceration, and thrombosis. In addition to discrete atherotic lesions, a localized and generalized sclerosis occurs. Sclerosis, or stiffness, can be demonstrated in experimental disease in animals and in man, and regression leads to reduced stiffness. Magnetic resonance imaging promises a comprehensive assessment of peripheral atherosclerosis noninvasively and without the use of ionizing radiation. Atheroma can be imaged directly, its size can be measured, its shape can be described, its lipid content can be assessed, and its effects upon vascular hemodynamics can be studied. In addition, arterial compliance, pulse wave velocity, and the pattern of flow within the vessel can be studied. It is thus a potential tool not only for the detection of disease but also for studying its natural history, risk factors, and the effects of pharmacological or surgical interventions.


The future of computer-assisted investigation of the polysomnogram: sleep microstructure.
Previous attempts at automated analysis of sleep were mainly directed towards imitating the Rechtschaffen and Kales rules (RKR) in order to save scoring time and further objectify the procedure. RKR, however, do not take into consideration the sleep microstructure of REM, stage 2, and SWS. While the microstructure of stage 2 has been analyzed in the past decade, the microstructure of REM and SWS are virtually unknown. In stage 2 the amount and distribution of spindles, K complexes, and arousal reactions have been studied. At least two types of spindles (12/s and 14/s) with different dynamics and locations have been identified. Two different shapes for K complexes have been described: one related to external sensory stimuli with similarities to evoked potentials and another one more related to sinusoidal slow wave activity seen in SWS. These two different K complex shapes have different distributions and, obviously, different functions. The authors also suggest that one should differentiate between arousal reactions and true arousals. Recent investigations suggest two types of delta waves in SWS. The more sinusoidal 1-3/s delta waves with a frontal maximum are already seen with lower amplitude in late stage 2 and increase their amplitude and incidence towards stage 3 and Stage 4. The other delta-wave type is slower (< 1/s), polymorphic, and has varying amounts of theta and higher frequency waves superimposed. During REM sleep it seems to be important to separate phases with rapid eye movements from those with none (REM sine REM), and count the amount and distribution of sawtooth activity. Background activity during REM and REM sine REM, as well as intra- and interhemispheric coherence should be analyzed separately. Only if the microstructure of the sleep EEG can be analyzed automatically using newer techniques such as transformation into wavelets and pattern classification with neuronal networks, and only if we learn more about the importance of microstructure elements, can automated sleep analysis go beyond the limited information obtained from scoring according to RKR.


Identification of plastics in cultural heritage collections by Fourier transform infrared spectroscopy (FTIR).
Infrared spectroscopy is the most commonly used analytical technique for identifying polymeric compounds, such as cellulose acetate, cellulose nitrate, polyurethane, Perspex, PVC and nylon in analytical laboratories. Other relevant techniques for identification include Raman spectroscopy (see Analytical Methods Committee, AMCTB No. 67) and pyrolysis gas chromatography mass spectrometry (Py-GCMS). This technical brief focuses on the application of FTIR spectroscopy and outlines the different types of materials commonly found in museum collections. The different types of attachments and techniques, which have been developed to address the various forms of materials and minimise the need for sampling, are also described here.


Emergency department bypass for ST-Segment-elevation myocardial infarction patients identified with a prehospital electrocardiogram: a report from the American Heart Association Mission: Lifeline program.
For patients identified before hospital arrival with ST-segment-elevation myocardial infarction, bypassing the emergency department (ED) with direct transport to the catheterization laboratory may shorten reperfusion times. We studied 12 581 ST-segment-elevation myocardial infarction patients identified with a prehospital ECG treated at 371 primary percutaneous coronary intervention-capable US hospitals participating in the Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With The Guidelines, including those participating in the American Heart Association Mission: Lifeline program from 2008 to 2011. Reperfusion times with primary percutaneous coronary intervention and in-hospital mortality rates were compared between patients undergoing ED evaluation and those bypassing the ED. ED bypass occurred in 1316 patients (10.5%). These patients had a lower frequency of heart failure and shock on presentation and nonsystem reasons for delay in percutaneous coronary intervention. ED bypass occurred more frequently during working hours compared with off-hours (18.3% versus 4.3%); ED bypass rate varied significantly across hospitals (median, 3.3%; range, 0%-71%). First medical contact to device activation time was shorter (median, 68 minutes [interquartile range, 54-85 minutes] versus 88 minutes [interquartile range, 73-106 minutes]; P<0.0001) and achieved within 90 minutes more frequently (80.7% versus 53.7%; P<0.0001) with ED bypass. The unadjusted in-hospital mortality rate was lower among ED bypass patients (2.7% versus 4.1%; P=0.01), but the adjusted mortality risk was similar (adjusted odds ratio, 0.69; 95% confidence interval, 0.45-1.03; P=0.07). Among ST-segment-elevation myocardial infarction patients identified with a prehospital ECG, the rate of ED bypass varied significantly across US hospitals, but ED bypass occurred infrequently and was mostly isolated to working hours. Because ED bypass was associated with shorter reperfusion times and numerically lower mortality rates, further exploration of and advocacy for the implementation of this process appear warranted.


Improving the performance of image classification by Hahn moment invariants.
The discrete orthogonal moments are powerful descriptors for image analysis and pattern recognition. However, the computation of these moments is a time consuming procedure. To solve this problem, a new approach that permits the fast computation of Hahn's discrete orthogonal moments is presented in this paper. The proposed method is based, on the one hand, on the computation of Hahn's discrete orthogonal polynomials using the recurrence relation with respect to the variable x instead of the order n and the symmetry property of Hahn's polynomials and, on the other hand, on the application of an innovative image representation where the image is described by a number of homogenous rectangular blocks instead of individual pixels. The paper also proposes a new set of Hahn's invariant moments under the translation, the scaling, and the rotation of the image. This set of invariant moments is computed as a linear combination of invariant geometric moments from a finite number of image intensity slices. Several experiments are performed to validate the effectiveness of our descriptors in terms of the acceleration of time computation, the reconstruction of the image, the invariability, and the classification. The performance of Hahn's moment invariants used as pattern features for a pattern classification application is compared with Hu [IRE Trans. Inform. Theory 8, 179 (1962)] and Krawchouk [IEEE Trans. Image Process.12, 1367 (2003)] moment invariants.


Beta-subunits promote the expression of Ca(V)2.2 channels by reducing their proteasomal degradation.
The β-subunits of voltage-gated calcium channels regulate their functional expression and properties. Two mechanisms have been proposed for this, an effect on gating and an enhancement of expression. With respect to the effect on expression, β-subunits have been suggested to enhance trafficking by masking an unidentified endoplasmic reticulum (ER) retention signal. Here we have investigated whether, and how, β-subunits affect the level of Ca(V)2.2 channels within somata and neurites of cultured sympathetic neurons. We have used YFP-Ca(V)2.2 containing a mutation (W391A), that prevents binding of β-subunits to its I-II linker and found that expression of this channel was much reduced compared with WT CFP-Ca(V)2.2 when both were expressed in the same neuron. This effect was particularly evident in neurites and growth cones. The difference between the levels of YFP-Ca(V)2.2(W391A) and CFP-Ca(V)2.2(WT) was lost in the absence of co-expressed β-subunits. Furthermore, the relative reduction of expression of Ca(V)2.2(W391A) compared with the WT channel was reversed by exposure to two proteasome inhibitors, MG132 and lactacystin, particularly in the somata. In further experiments in tsA-201 cells, we found that proteasome inhibition did not augment the cell surface Ca(V)2.2(W391A) level but resulted in the observation of increased ubiquitination, particularly of mutant channels. In contrast, we found no evidence for selective retention of Ca(V)2.2(W391A) in the ER, in either the soma or growth cones. In conclusion, there is a marked effect of β-subunits on Ca(V)2.2 expression, particularly in neurites, but our results point to protection from proteasomal degradation rather than masking of an ER retention signal.


Cytokine-induced immune complex binding to the high-affinity IgG receptor, FcγRI, in the presence of monomeric IgG.
FcγRI is the sole high-affinity immunoglobulin G (IgG) receptor on leukocytes. Its role in immunity and the clearance of opsonized particles has been challenged, as the receptor function may well be hindered by serum IgG. Here, we document immune complex binding by FcγRI to be readily enhanced by cytokine stimulation, whereas binding of monomeric IgG only modestly increased. Enhanced immune complex binding was independent of FcγRI surface expression levels. FcγRI, saturated with prebound IgG, was found capable of effective immune complex binding upon cytokine stimulation. Cytokine-enhanced binding was observed across a variety of immune complexes, including huIgG3- or mIgG2a-opsonized red blood cells, rituximab- or ofatumumab-opsonized B-cell lymphoma, and cetuximab-opsonized glioblastoma cells. This study contributes to our understanding of how FcγRI can participate in the clearance of opsonized particles despite saturation by monomeric IgG.


Impact of guideline-consistent therapy on outcome of patients with healthcare-associated and community-acquired pneumonia.
A new category of healthcare-associated pneumonia (HCAP) has been added in the most recent American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines, since multidrug-resistant (MDR) pathogens are more common in patients with HCAP than in those with community-acquired pneumonia (CAP). The optimal empirical management of patients with HCAP remains controversial and adherence to guidelines is inconsistent. A retrospective cohort study of 3295 adults admitted for pneumonia in an academic centre of Canada, between 1997 and 2008. MDR pathogens were more common among patients with HCAP than in those with CAP, but less so than in other studies. Compared with patients with CAP, those with HCAP had a higher all-cause 30 day mortality [68/563 (12%) versus 201/2732 (7%); P < 0.001] and more frequent need for mechanical ventilation [78/563 (14%) versus 276/2732 (10%); P = 0.01]. In patients with CAP, mortality was lower when treatment was concordant with guidelines [86/1557 (6%) versus 109/1097 (10%) if discordant; adjusted odds ratio 0.6 (0.4-0.8); P < 0.001]. In HCAP, mortality was similar whether or not empirical treatment was concordant with guidelines [6/35 (17%) versus 18/148 (12%) if discordant; P = 0.4]. However, 30 day mortality tended to be higher when the empirical treatment was microbiologically ineffective [4/22 (18%) versus 17/187 (9%) when effective; P = 0.3]. HCAP is associated with worse outcomes than CAP. MDR pathogens were implicated in only a small fraction of HCAP cases. In our study, unlike CAP, non-respect of current HCAP guidelines had no adverse effect on the ultimate outcome. Strategies for the empirical management of HCAP should be tailored to the local epidemiological context.


Selexipag for the treatment of pulmonary arterial hypertension.
The pharmacology, pharmacokinetics, clinical efficacy, safety and tolerability, dosing and administration, and place in therapy of selexipag, an orally administered selective prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension (PAH), are reviewed. The first-in-class oral prostacyclin IP receptor agonist selexipag (Uptravi, Actelion Pharmaceuticals) was approved by the Food and Drug Administration in December 2015. Selexipag is rapidly hydrolyzed to a long-acting metabolite that binds with high selectivity to IP receptors, resulting in vasodilation, inhibition of platelet aggregation, and antiinflammatory effects. Results of a long-term, placebo-controlled, clinical outcomes-driven trial showed that selexipag significantly reduced the occurrence of the composite primary outcome (all-cause mortality and development of PAH-related complications). Selexipag is indicated for use in patients with World Health Organization functional class (FC) II or III disease. The recommended initial selexipag dosage is 200 μg twice daily. Like prostanoid analogs, selexipag has a dose-dependent adverse-effect profile that includes nausea, vomiting, diarrhea, headache, and musculoskeletal pain. Although selexipag offers distinct pharmacologic advantages over other agents for the treatment of PAH, important issues of cost and access must be considered. Selexipag is an oral prostacyclin IP receptor agonist approved for use as monotherapy or in combination with other therapies to slow PAH progression and reduce the risk of hospitalization in patients with FC II or III symptoms. Its stability and relatively long half-life offer conveniences over conventional prostanoid therapies.


Solanum nigrum: a model ecological expression system and its tools.
Plants respond to environmental stresses through a series of complicated phenotypic responses, which can be understood only with field studies because other organisms must be recruited for their function. If ecologists are to fully participate in the genomics revolution and if molecular biologists are to understand adaptive phenotypic responses, native plant ecological expression systems that offer both molecular tools and interesting natural histories are needed. Here, we present Solanum nigrum L., a Solanaceous relative of potato and tomato for which many genomic tools are being developed, as a model plant ecological expression system. To facilitate manipulative ecological studies with S. nigrum, we describe: (i) an Agrobacterium-based transformation system and illustrate its utility with an example of the antisense expression of RuBPCase, as verified by Southern gel blot analysis and real-time quantitative PCR; (ii) a 789-oligonucleotide microarray and illustrate its utility with hybridizations of herbivore-elicited plants, and verify responses with RNA gel blot analysis and real-time quantitative PCR; (iii) analyses of secondary metabolites that function as direct (proteinase inhibitor activity) and indirect (herbivore-induced volatile organic compounds) defences; and (iv) growth and fitness-estimates for plants grown under field conditions. Using these tools, we demonstrate that attack from flea beetles elicits: (i) a large transcriptional change consistent with elicitation of both jasmonate and salicylate signalling; and (ii) increases in proteinase inhibitor transcripts and activity, and volatile organic compound release. Both flea beetle attack and jasmonate elicitation increased proteinase inhibitors and jasmonate elicitation decreased fitness in field-grown plants. Hence, proteinase inhibitors and jasmonate-signalling are targets for manipulative studies.


No difference at two years between all inside transtibial technique and traditional transtibial technique in anterior cruciate ligament reconstruction.
one of the most recent technique is the "all inside" anterior cruciate ligament (ACL) reconstruction. One of the main characteristic of this procedure is the sparing of the tibial cortex. Furthermore, the all-inside technique requires only one tendon harvested. the present study describes two year clinical outcomes of the all-inside method for ACL reconstruction, and compares them with clinical results of a group of patients treated with the traditional transtibial single-bundle ACL reconstruction technique using the semitendinosus and gracilis tendons (ST-G). pilot study, using historical controls. ACL reconstruction was performed on two groups of 20 patients each. The patients in one group underwent the all-inside transtibial technique with ST tendon alone. The second group underwent ACL reconstruction with the traditional transtibial single-bundle procedure using quadrupled ST-G tendons. Follow up at 24 months was undertaken using the IKDC, VAS pain score, Lysholm and Tegner scales. the VAS pain score for the traditional ACL group was 84.6 ± 12.6; whereas the score for the all-inside group was 81.6 ± 13.1, with no statistically significant differences between the two groups. In the traditional ACL reconstruction group the Lysholm scale gave a "good results" for 7 patient (35%) and "excellent results" for 13 patients (65%) and the all-inside group gave "sufficient results" for 4 patients (20%), "good results" for 7 patients (35%) and "excellent results" for 9 patients (45%) (n.s.). The median of Tegner score was 6.5 (2-10) for the standard method group and 6 (1-9) for the all-inside group (n.s). The IKDC evaluated 50% of patients from the standard technique group as class A, and 45% as class B and 5% as class C. As regards patients of the all inside technique 55% were class A, 40% class B and, here too, just 5% scored as class C. No patients were classed as group D in each group. this study suggests that, in respect to return to sports and adequate articular function, there are no differences between the all-inside transtibial ACL reconstruction technique and the traditional transtibial ACL reconstruction using ST-G. The role of all-inside transtibial ACL reconstruction remains dubious. III or Level C according with Oxford Center of EBM.


Nuclear factor-kappa B regulates pain and COMT expression in a rodent model of inflammation.
Nuclear factor-kappa B (NF-κB) is a ubiquitously expressed protein complex regulating the transcription of genes involved in inflammation and pain. Increased NF-κB activity in immune and nervous system cells is linked to several chronic pain conditions in humans as well as inflammation and nerve injury-evoked pain in animals. A recent in vitro study further demonstrates that increased NF-κB activity in astrocytes decreases transcription of catechol-o-methyltransferase (COMT), an enzyme that inactivates catecholamines that cause pain. The purpose of the present study was to examine the relationship between systemic and astrocytic NF-κB activity, pain, and COMT expression in an animal model of inflammation. Results demonstrated that administration of the inflammatory stimulant complete Freund's adjuvant (CFA) led to increased pain and decreased COMT protein expression in an NF-κB-dependent manner. Specifically, we found that rats and mice receiving intraplantar CFA exhibited increased behavioral responses to mechanical and thermal heat stimuli. CFA-evoked pain was blocked in rats receiving a pre-emptive systemic dose of the NF-κB inhibitor MG132 and exacerbated in IKKca mice with constitutive NF-κB activity in astrocytes. Furthermore, we observed NF-κB-linked reductions in COMT expression in midbrain at 6h and 1d following CFA in rats and at 1h and 1d in forebrain and midbrain following CFA in IKKca mice. Collectively, these results demonstrate that systemic and astrocytic NF-κB activity drive inflammatory pain and regulate the expression of COMT in forebrain and midbrain structures.


Comparison of Male and Female Resident Milestone Assessments During Emergency Medicine Residency Training: A National Study.
A previous study found that milestone ratings at the end of training were higher for male than for female residents in emergency medicine (EM). However, that study was restricted to a sample of 8 EM residency programs and used individual faculty ratings from milestone reporting forms that were designed for use by the program's Clinical Competency Committee (CCC). The objective of this study was to investigate whether similar results would be found when examining the entire national cohort of EM milestone ratings reported by programs after CCC consensus review. This study examined longitudinal milestone ratings for all EM residents (n = 1,363; 125 programs) reported to the Accreditation Council for Graduate Medical Education every 6 months from 2014 to 2017. A multilevel linear regression model was used to estimate differences in slope for all subcompetencies, and predicted marginal means between genders were compared at time of graduation. There were small but statistically significant differences between males' and females' increase in ratings from initial rating to graduation on 6 of the 22 subcompetencies. Marginal mean comparisons at time of graduation demonstrated gender effects for 4 patient care subcompetencies. For these subcompetencies, males were rated as performing better than females; differences ranged from 0.048 to 0.074 milestone ratings. In this national dataset of EM resident milestone assessments by CCCs, males and females were rated similarly at the end of their training for the majority of subcompetencies. Statistically significant but small absolute differences were noted in 4 patient care subcompetencies.