The distribution, abundance, and the effects of fire on mound building termites (Trinervitermes and Cubitermes spp., Isoptera: Termitidae) in northern guinea savanna West Africa.
Termite mound densities in typical guinea savanna, Detarium, and grassland (boval) habitats in northern guinea savanna were determined by random quadratting of 2-3 sites in each habitat (100, 10x10 m quadrats per habitat). Dominant species in guinea savanna were T. geminatus (46 mounds ha-1) and T. oeconomus (21 mounds ha-1), in Detarium T. geminatus (59 mounds ha-1) and C. curtatus (45 mounds ha-1) and in boval C. curtatus (72 mounds ha-1) and T. geminatus (22 mounds ha-1). Only C. curtatus densities and total densities differed significantly between sites within habitats, but all species differed significantly in abundance between habitats. The composition of each community was related to general environment but no particular environmental variable was shown to be a major determinant of termite distribution. Evidence for the limitation of termite populations was obtained from indirect evidence of competition between colonies in Detarium, and by experimental manipulation of fire regimes in the typical guinea savanna habitat. Harvester termites increased four-five fold over two years in fire-protected plots as a result of increased food supplies. Total termite densities in the fire-protected community equilibrated to the new population density (100 mounds ha-1) after only two-three years.


Occurrence ofpenicillium expansum and patulin in apples as raw materials for processing of foods - case study.
The contamination of apples Gloster variety withPenicillium expansum was investigated in the case study. The apples serve as a raw material in thefood industry for processing of baby foodstuffs and other apple products. The core of 3 - 5 % apple samples has been contaminated with spores and mycelium of untested microfungi. The surface tissue of stored apples has not been damaged. Penicillium expansum was isolated in all tested apple samples. Patulin has been found at levels tens to hundreds of üg/kg in tested apple samples. Patulin was primarily associated with core and areas of decomposing tissue and can penetrate up to approx. 1 cm of the surrounding healthy tissue. The production of patulin after the experimental contamination of apples was tested after 14 days of storage (21 °C, dark). The maximum value of patulin was found 110 mg/kg of rotten part of apple sample.


Norwegian health personnel's contacts and referrals for children of ill parents: an exploratory cross-sectional multi-centre study.
In 2010, changes were made to the Norwegian Health Personnel Act. This led to all health personnel being obliged to support the patients' children and families. The aims of this study were to investigate whether health personnel contacted or referred the patients' children to family/friends or public services. We also investigated if there were factors in the family or the services that increased or decreased the degree of contacts and referrals. In addition the patients were asked whether the law had been a help or even a burden. This study was part of a larger multi-site study of children of ill parents conducted in five health trusts in Norway. We used cross-sectional data from 518 patients and 278 health personnel. The informants completed a questionnaire addressing the law. Data were analyzed by factor analysis and logistic regression. The health personnel contacted/referred children to different services, but not to the degree desired by their parents. Only a few contacted family/friends, or the school and/or the public health nurse, those representing the helpers who live closest to the child, and thus well situated to participate in help and preventive efforts. The service most often referred to was the child welfare service. The results indicate a change in contacts/referrals for children from their parents' health personnel but also reveal remaining needs for support/help for these children. Health personnel should strive to write more referrals and take more contacts than the current study suggests, to secure adequate support for children of ill parents in Norway, as intended in The Health Personnel Act.


Dp71Δ78-79 dystrophin mutant stimulates neurite outgrowth in PC12 cells via upregulation and phosphorylation of HspB1.
PC12 cells acquire a neuronal phenotype in response to nerve growth factor (NGF). However, this phenotype is more efficiently achieved when the Dp71Δ78-79 dystrophin mutant is stably expressed in PC12-C11 cells. To investigate the effect of Dp71Δ78-79 overexpression on the protein profile of PC12-C11 cells, we compared the expression profiles of undifferentiated and NGF-differentiated PC12-C11 and PC12 cells by 2DE. In undifferentiated cultures, one protein was downregulated, and five were upregulated. Dp71Δ78-79 overexpression had a greater effect on differentiated cultures, with ten proteins downregulated and seven upregulated. The protein with the highest upregulation was HspB1. Changes in HspB1 expression were validated by Western blot and immunofluorescence analyses. Interestingly, the neurite outgrowth in PC12-C11 cells was affected by a polyclonal antibody against HspB1, and the level of HspB1 and HspB1Ser86 decreased, suggesting an important role for this protein in this cellular process. Our results show that Dp71Δ78-79 affects the expression level of some proteins and that the stimulated neurite outgrowth produced by this mutant is mainly through upregulation and phosphorylation of HspB1.


Genetic factors affecting susceptibility to udder pathogens.
Many studies have identified genetic factors underlying resistance or susceptibility to mastitis in dairy cows and heifers. Some authors focused on polygenic variation while others searched for genes and/or quantitative trait loci with major effects on mastitis. Classical traits related to mastitis include somatic cell counts, electrical conductivity and clinical cases of the disease. With the development of automatic milking devices and '-omics' technologies, new traits are considered, such as acute phase proteins, immunological assays, and milk flow patterns, and new biological pathways are discovered, for example the role of mammary epithelium and the nervous system. The usefulness of these traits for the identification of resistant cows is discussed in relation to the biological mechanisms underlying the development of the disease. In addition, the utility of these traits for genetic improvement is reviewed. Finally, the problem of durability in resistance is addressed, including co-evolution and the cost of resistance.


Comparing patient outcomes between multiple ipsilateral iliac artery stents and isolated iliac artery stents.
Endovascular stents are accepted therapy for iliac artery stenoses and occlusions. Surgery is the recommended therapy for patients with severe iliac artery disease, including those with the combination of ipsilateral common iliac artery (CIA) and external iliac artery (EIA) stenoses/occlusions. This study compared patient outcomes, including late open conversion rates, for combined ipsilateral CIA and EIA stenting vs CIA or EIA stents alone. Between 1998 and 2010, 588 patients underwent iliac artery stenting at two institutions. Patient comorbidities and outcomes were retrospectively reviewed, and analyses were performed using multivariate regression and Kaplan-Meier methods. There were 436 extremities with CIA stents, 195 with EIA stents, and 157 with CIA and EIA stents. The groups did not differ significantly in demographics, comorbidities, or treatment indications. During follow-up, 183 patients died, 95 underwent an endovascular reintervention, and 48 required late open conversion. For patients in the CIA or EIA stent group, the mean ± standard error survival was 5.3 ± 0.3 years, secondary endovascular intervention-free survival was 7.4 ± 0.6 years, late open conversion-free survival was 9.8 ± 0.4 years, and amputation-free survival was 7.6 ± 0.4 years. In the CIA and EIA stent group, survival was 6.1 ± 0.6 years, secondary endovascular intervention-free survival was 7.2 ± 0.6 years, late open conversion-free survival was 9.0 ± 1.1 years, and amputation-free survival was 8.4 ± 0.5 years. Survival, reintervention-free survival, late open conversion-free survival, and amputation-free survival were all similar between patient groups (all P > .05). CIA and EIA stenting in combination was not a predictor of death, reintervention, late open conversion, or amputation. Outcomes are similar for patients with CIA or EIA stents and for those with combined ipsilateral CIA and EIA stents. Late open conversions for iliac artery stent failure are uncommon and not influenced by the location or extent of prior iliac artery stent placement. Endovascular therapy for aortoiliac disease should be extended to consider selected patients with ipsilateral CIA and EIA stenoses/occlusions.


Altered local cerebral glucose utilization induced by electrical stimulations of the thalamic sensory and parafascicular nuclei in rats.
Alterations in local cerebral glucose utilization (LCGU) induced by electrical stimulation of the sensory relay nucleus (VPL) or parafascicular nucleus (Pf) of the thalamus in conscious rats were measured by the [14C]2-deoxyglucose method, the objective being to assess the mechanism of analgesia induced by electrical stimulations of these structures. Stimulation of the VPL induced an ipsilateral increase in LCGU in the sensory thalamic nucleus itself, the sensory cortex and substantia nigra. Stimulation of the Pf induced bilateral increases in LCGU in the Pf and central medial nucleus of the thalamus, sensory cortex, ventral areas of the striatum and substantia nigra, and ipsilateral increase in LCGU in the periaqueductal gray, parabrachial pontine nucleus and deep layers of the superior colliculus. No significant change in LCGU was detected in the raphe dorsalis, raphe magnus and spinal dorsal horn, in both groups. Our observations coincide with clinical findings that unilateral electrical stimulation of the Pf leads to amelioration of intractable pain bilaterally, while that of the VPL induces an analgesia restricted to the contralateral side.


A Sialylated-Bortezomib Prodrug Strategy Based on a Highly Expressed Selectin Target for the Treatment of Leukemia or Solid Tumors.
This study aimed to explore the potential of sialic acid - related selectin targeting strategy in the treatment of leukemia and some solid tumors. We expected it could "actively" bind tumor cells and kill them, reducing non-specific toxicity to normal cells. BOR-SA prodrug was synthesized by reacting an ortho-dihydroxy group in SA with a boronic acid group in BOR. Two kinds of leukemia cells (RAW264.7 and HL60 cells), one solid sarcoma cell model (S180 cells) and their corresponding normal cells (monocytes (MO), neutrophil (NE) and fibroblast (L929)) were selected for the in vitro cell experiments (cytotoxicity, cellular uptake, cell cycle and apoptosis experiments). The S180 tumor-bearing Kunming mice model was established for anti-tumor pharmacodynamic experiments. In vitro cell assay results showed that uptake of BOR-SA by HL60 and S180 cells were increased compared with the control group. BOR-SA induced a lower IC50, higher ratio of apoptosis and cell cycle arrest of tumor cells. In vivo anti-S180 tumor pharmacodynamics experiments showed that mice in the BOR-SA group had higher tumor inhibition rate, higher body weight and lower immune organ toxicity compared with the control group. sialic acid-mediated selectin targeting strategy may have great potential in the treatment of related tumors.


In search of "the white area": some notes on art in clinical space.
Would you consider looking at two paintings instead of reading a more ritualized abstract? In the first painting, the poet W. B. Yeats shows passages from his autobiography to his friend, the poet and painter George Russell. Russell is appalled to read that there is hardly a single fact accurate: "If you show me the manuscript," he tells Yeats, "I will correct the facts." Yeats airily dismisses the offer: "Oh, I do not want accuracy. I only want a picturesque sentence" (Kiberd, 2003). The second painting is an image I cherish in my mind for years: a photo of the Teatro del Mondo (the theater of the world) created by Aldo Rossi, the late Italian architect, for the 1979 Venice Biennale. Built in the Venice tradition of floating theaters, Rossi created a theater on water, a raft tugged by a boat. Within the panoramic view of Venice, there is a "huge piece of carpentry," which looks like a stageset of a child's dream memory: some big connected play-cubes made of light brown wood on a metal grid of scaffolding, and a blue pointed tower. For Rossi, this theater goes beyond the context of Venice. It is like "the Marine buildings in Maine, the wonderful tall light houses--'the houses of the light'--that observe and are observed...[in a] Venetian method of construction...that seeks fantasy only in the real" (Rossi, 1979).


Identification, expression patterns, evolutionary characteristics and recombinant protein activities analysis of CD209 gene from Megalobrama amblycephala.
CD209 is a type II transmembrane protein in the C-type lectin family, which is involved in the regulation of innate and adaptive immune system. Although it has been widely studied in mammals, but little has been reported about fish CD209 genes. In the present study, Megalobrama amblycephala CD209 (MaCD209) gene was cloned and characterized, its expression patterns, evolutionary characteristics, agglutinative and bacteriostatic activities were analyzed. These results showed that the open reading frame (ORF) of MaCD209 gene was 795 bp, encoding 264 aa, and the calculated molecular weight of the encoded protein was 29.7 kDa. MaCD209 was predicted to contain 2 N-glycosylation sites, 1 functional domain (C-LECT-DC-SIGN-like) and 1 transmembrane domain. Multiple sequence alignment showed that the amino acid sequence of MaCD209 was highly homologous with that of partial fishes, especially the highly conserved C-LECT-DC-SIGN-like domain and functional sites of CD209. Phylogenetic analysis showed that the CD209 genes from M. amblycephala and other cypriniformes fishes were clustered into one group, which was reliable and could be used for evolutionary analysis. Then, adaptive evolutionary analysis of teleost CD209 was conducted, and several positively selected sites were identified using site and branch-site models. Quantitative real-time PCR analysis showed that MaCD209 gene was highly expressed in the liver and heart. Moreover, the expression of MaCD209 was significantly induced upon Aeromonas hydrophila infection, with the peak levels at 4 h or 12 h post infection. The immunohistochemical analysis also revealed increased distribution of MaCD209 protein post bacterial infection. In addition, recombinant MaCD209 (rMaCD209) protein was prepared using a pET32a expression system, which showed excellent bacterial binding and agglutinative activities in a Ca2+-independent manner. However, rMaCD209 could only inhibit the proliferation of Escherichia coli rather than A. hydrophila. In conclusion, this study identified the MaCD209 gene, detected its expression and evolutionary characteristics, and evaluated the biological activities of rMaCD209 protein, which would provide a theoretical basis for understanding the evolution and functions of fish CD209 genes.


Doppler echocardiographic evaluation of pulmonary regurgitation facilitates the diagnosis of constrictive pericarditis.
Diagnosing constrictive pericarditis (CP) remains a clinical challenge. Ventricular interdependence and dissociation of intrathoracic and intracardiac pressures are hallmark features that are readily recognized by invasive and noninvasive hemodynamics. The Doppler echocardiographic signal from pulmonic valve regurgitation depends on the relationship between pulmonary artery (intrathoracic) and right ventricular (intracardiac) pressure. Respiration-associated changes in this signal may aid in the evaluation of pericardial constriction. We demonstrate here that early diastolic cessation with inspiration can indicate a CP process. Early diastolic cessation with inspiration was shown to have correctly diagnosed CP in 70% of the patients in this study, with a sensitivity of 77%, specificity of 64%, positive predictive value of 67%, and negative predictive value of 75%. This noninvasive insight into dissociation of intracardiac and intrathoracic pressures, although not sufficient on its own, may be a valuable tool for aiding in the diagnosis of CP.


Development and Validation of a Post-Radiotherapy Prediction Model for Bowel Dysfunction After Rectal Cancer Resection.
The benefit of radiotherapy for rectal cancer is based largely on a balance between a decrease in local recurrence and an increase in bowel dysfunction. Predicting postoperative disability is helpful for recovery plans and early intervention. We aimed to develop and validate a risk model to improve the prediction of major bowel dysfunction after restorative rectal cancer resection with neoadjuvant radiotherapy using perioperative features. Eligible patients more than 1 year after restorative resection following radiotherapy were invited to complete the low anterior resection syndrome (LARS) score at 3 national hospitals in China. Clinical characteristics and imaging parameters were assessed with machine learning algorithms. The post-radiotherapy LARS prediction model (PORTLARS) was constructed by means of logistic regression on the basis of key factors with proportional weighs. The accuracy of the model for major LARS prediction was internally and externally validated. A total of 868 patients reported a mean LARS score of 28.4 after an average time of 4.7 years since surgery. Key predictors for major LARS included the length of distal rectum, anastomotic leakage, proximal colon of neorectum, and pathologic nodal stage. PORTLARS had a favorable area under the curve for predicting major LARS in the internal dataset (0.835; 95% CI, 0.800-0.870, n = 521) and external dataset (0.884; 95% CI, 0.848-0.921, n = 347). The model achieved both sensitivity and specificity >0.83 in the external validation. In addition, PORTLARS outperformed the preoperative LARS score for prediction of major events. PORTLARS could predict major bowel dysfunction after rectal cancer resection following radiotherapy with high accuracy and robustness. It may serve as a useful tool to identify patients who need additional support for long-term dysfunction in the early stage. gov, number NCT05129215.


A genetic study of the anesthetic response: mutants of Drosophila melanogaster altered in sensitivity to halothane.
In an attempt to identify genes that control or encode the targets of general anesthetics, we have chemically mutagenized fruit flies and selected four lines that show an abnormal response to the volatile anesthetic halothane. Specifically, about 2-fold higher concentrations of halothane are required to induce the loss of motor control in the mutant flies. Fine mapping of two isolates indicates that they alter a previously uncharacterized gene of Drosophila. In the absence of anesthetics, these mutants display alterations of behavior that imply changes in the adult and the larval neuromuscular system.


Guineafowl with a twist: asymmetric limb control in steady bipedal locomotion.
In avian bipeds performing steady locomotion, right and left limbs are typically assumed to act out of phase, but with little kinematic disparity. However, outwardly appearing steadiness may harbor previously unrecognized asymmetries. Here, we present marker-based XROMM data showing that guineafowl on a treadmill routinely yaw away from their direction of travel using asymmetrical limb kinematics. Variation is most strongly reflected at the hip joints, where patterns of femoral long-axis rotation closely correlate to degree of yaw divergence. As yaw deviations increase, hip long-axis rotation angles undergo larger excursions and shift from biphasic to monophasic patterns. At large yaw angles, the alternately striding limbs exhibit synchronous external and internal femoral rotations of substantial magnitude. Hip coordination patterns resembling those used during sidestep maneuvers allow birds to asymmetrically modulate their mediolateral limb trajectories and thereby advance using a range of body orientations.


Intraperitoneal administration of thioredoxin decreases brain damage from ischemic stroke.
Recent studies demonstrate that Thioredixin (Trx) possesses a neuronal protective effect and closely relates to oxidative stress and apoptosis of cerebral ischemia injury. The present study was conducted to validate the neuroprotective effect of recombinant human Trx-1 (rhTrx-1) and its potential mechanisms against ischemia injury at middle cerebral artery occlusion (MCAO) in mice. rhTrx-1 was administrated intraperitoneally at a dose of 5, 10 and 20mg/kg 30 min before MCAO in mice, and its neuronal protective effect was evaluated by neurological deficit score, brain dry-wet weight, 2,3,5-triphenyltetrazolium chloride (TTC) staining. The protein carbonyl content and HO-1 were detected to investigate its potential anti-oxidative and anti-inflammatory property, and the anti-apoptotic ability of rhTrx-1 was assessed by casepase-3 and TUNEL staining. The results demonstrated that rhTrx-1 significantly improved neurological functions and reduced cerebral infarction and apoptotic cell death at 24h after MCAO. Moreover, rhTrx-1 resulted in a significant decrease in carbonyl contents and HO-1 against oxidative stress, which turned to be fast reduction during the first 24h and tended to be stable from 24h to 72h after MCAO. The study shows that rhTrx-1 exerts an neuroprotective effect in cerebral ischemia injury. The anti-oxidative, anti-apoptotic and anti-inflammatory properties of rhTrx-1 are more likely to succeed as a therapeutic approach to diminish oxidative stress-induced neuronal apoptotic cell death in acute ischemic stroke.


A Controlled, Randomized Clinical Study on the Impact of Treatment on Antral Mucociliary Clearance: Uncinectomy Versus Balloon Sinuplasty.
To find out the effect of minimal invasive sinus surgery and balloon sinuplasty on mucociliary clearance and compare different methods of measuring mucociliary clearance. Twenty-nine patients with chronic rhinosinusitis were randomized in 2 operative groups (uncinectomy or balloon sinuplasty). Before and 6 months after the treatment, patients filled out a quality of life questionnaire (Sino Nasal Outcome Test-22 [SNOT-22]), and mucociliary clearance was measured with endoscope and gamma camera after 0.03 ml of saccharine, methylene-blue dye, and human albumin labeled with Tc99m was introduced to the bottom of maxillary sinuses. In uncinectomy group, SNOT-22 score decreased, but treatment had no effect on mucociliary clearance. Based on saccharine test, smoking was associated with worse mucociliary clearance (r = 0.618, P < .05). Methylene blue test results associated with saccharine test (r = 0.434, P < .05) and Tc99m-labeled tracer technique (r = 0.261, P = .039) separately. Treatment positively affects patients' quality of life; however, it has no effect on mucociliary clearance. There was a statistically significant correlation between the Tc99m-labeled tracer technique and the methylene blue technique. The saccharine technique was even less accurate, but it can be useful in clinical practice because it is a quick, easy, and safe technique.


[The effects of postoperative continuous epidural analgesia after laparoscopy-assisted distal gastrectomy].
This study was conducted to evaluate the effects of continuous epidural analgesia on the postoperative pain and the early recovery after laparoscopy-assisted gastrectomy (LAG). A total of 66 patients undergoing elective LAG were investigated for postoperative pain score and other variables retrospectively. Forty-four patients who had received epidural analgesia (E group) showed significantly lower pain scores for 2, 12 and 48 hours after surgery, compared with 22 patients who had received analgesics intramuscularly or transrectally (C group). The patients in the E group needed significantly less supplemental analgesics than those in C group for 2 and 12 hours after the operation. The early recovery and the incidence of postoperative complications were not significantly different between the two groups. These results show that postoperative continuous epidural analgesia is effective for postoperative pain relief in patients after laparoscopy-assisted gastrectomy.


Experimental allergic neuritis. Humoral and cellular immune responses to the cyanogen bromide peptides of the P2 protein.
Lewis rats were immunized with P2 protein and peptides CN1, CN2 and CN3. In P2 immunized rats, antibody and cellular sensitivity to the P2 protein were seen prior to the appearance of clinical signs of EAN, during disease and during recovery. CN1 immunized rats had equal or more severe clinical and histological signs of EAN but lower antibody titers than P2 immunized animals. CN-1 elicited a greater blastogenic response in both P2 and CN-1 immunized animals. CN-2 and CN-3 immunized rats showed little clinical and histological evidence of EAN and no antibody. However, lymphocytes sensitive to the immunizing antigen and the P2 protein were present.


[Outpatient parenteral antibiotic therapy (OPAT): the Lausanne experience supporting new perspectives].
With the increase of infections without option for an oral treatment, the systematic use of hospitalization overloads the healthcare system and causes growing political concern. For carefully selected patients, outpatient parenteral antibiotic therapy is an interesting alternative, with more than 40 years of experience in several countries. In this perspective, an outpatient parenteral antibiotic therapy (OPAT) unit was established in Lausanne two years ago. This article aims to describe its activity. Its practice, involving especially self-administration, seems to be safe, efficacious and cost-effective, as long as international good practice recommendations are applied.


Health literacy: a policy challenge for advancing high-quality health care.
Health literacy, at the intersection of health and education, involves more than reading ability. Studies of health literacy abilities show that many Americans with the greatest health care needs have the least ability to comprehend information required to navigate and function in the U.S. health care system. This paper defines health literacy as an important policy issue and offers strategies for creating a health-literate America.


Occurrence and extracellular actions of inositol pentakis- and hexakisphosphate in mammalian brain.
Although inositol 1,3,4,5,6-pentakisphosphate (InsP5) and hexakisphosphate (InsP6) have been recognized for some time as naturally-occurring metabolites of inositol, their occurrence in mammalian cell types, including one of neural origin, has only recently been documented. This is of interest because of the recognized second messenger role of inositol 1,4,5-trisphosphate (InsP3) in intracellular signalling; coupling surface stimuli to cytoplasmic calcium discharge. The metabolism, existence in normal mature tissues, and possible functional roles of these inositol polyphosphates are unknown. Here we report evidence that InsP5 and InsP6 are synthesized in intact brain after labelling with [3H]inositol in vivo. We also show that local infusion of InsP5 and InsP6 into a discrete brain stem nucleus implicated in cardiovascular regulation, results in dose-dependent changes in heart rate and blood pressure.


Risk factors for brain metastasis in patients with small cell lung cancer without prophylactic cranial irradiation.
This study aimed to determine the risk factors for brain metastasis (BM) and the prognostic factors for overall survival (OS) in patients with small cell lung cancer without prophylactic cranial irradiation (PCI). Limited stage small cell lung cancer (LS-SCLC) patients achieving a complete response (CR) or partial response (PR) were enrolled into this study between January 2010 and December 2016. We retrospectively evaluated the influencing factors for time to BM and overall survival (OS). A total of 153 patients were enrolled into this study. Sixty-eight developed BM during the follow-up period. For the whole cohort, the 1‑ and 2‑year BM rates were 29.4 and 41.2%, respectively. Multivariate analysis showed that T stage (hazard ratio [HR] = 2.27, P = 0.024), neutrophil-to-lymphocyte ratio (NLR; HR = 2.07, P = 0.029), time to thoracic radiotherapy (HR = 0.34, P = 0.002) and chemotherapy cycles (HR = 0.49, P = 0.036) were the independent influencing factors of time to BM. Only NLR (HR = 2.11, P = 0.005) and time to thoracic radiotherapy (HR = 1.95, P = 0.011) were independent prognostic factors of OS. Of the 68 patients developing BM, those with BM occurring as the first relapse (42/68) had better OS than the others (39.5 months vs 23.0 months, P = 0.016). LS-SCLC patients without PCI had a high risk of BM. High T stage, high NLR, early thoracic radiotherapy and fewer chemotherapy cycles were the risk factors of BM. Further research is needed to confirm the results.


Changing livestock vaccination policy alters the epidemiology of human anthrax, Georgia, 2000-2013.
Anthrax is a widely spread zoonotic disease found on nearly every continent. To control the disease in humans and animals, annual livestock vaccination is recommended. However, in 2007, the country of Georgia ended its policy of compulsory annual livestock anthrax vaccination. Our objective was to assess how the epidemiology of human anthrax has evolved from 2000-2013 in Georgia, in the wake of this cessation. We used passive surveillance data on epidemiological surveys of human anthrax case patients. Risk factors and rates of self-reported sources of infection were compared, before and after the change in livestock vaccination policy. We mapped ethnicity-adjusted incidence during the two periods and assessed changes in the spatial pattern of risk. The overall risk of human anthrax increased >5-fold, from 0.7 cases per 100,000 in 2000 to 3.7 cases per 100,000 by 2013. Ethnic disparities in risk became pronounced; from 2000 to 2013, incidence increased >60-fold in Azerbaijanis from 0.35 to 21.1 cases/100,000 Azerbaijanis compared to 0.61 to 1.9 cases/100,000 among ethnic Georgians. Food-borne exposures from purchasing meat increased from 11% in 2000-2006 to 21% in 2007-2013. Spatial analyses revealed a shift from a random pattern of reporting pre-policy change to clustering among district municipalities following the change in policy. Our findings indicate there were unintended human health consequences associated with changing livestock vaccination policy. Following a reduction in the immunizations administered, there was a major shift in the epidemiology of human anthrax in Georgia. Current infection risk is now highest among ethnic minorities. Increased reporting among individuals uncharacteristically at risk for anthrax from foodborne exposures suggests spillover from modes of agricultural production. Given the importance of human-livestock health linkages, careful evaluations of policy need to be undertaken before changes to animal vaccination are made.


Age-related differences in clinical outcomes for acute asthma in the United States, 2006-2008.
Little is known about the effect of age on acute asthma outcomes. We sought to investigate age-related differences in the emergency department (ED) presentation and clinical outcomes for patients with acute asthma. We analyzed the 2006-2008 Nationwide Emergency Department Sample, the largest, all-payer, US ED and inpatient database. ED visits for acute asthma were identified with a principal diagnosis of International Classification of Disease, ninth revision, Clinical Modification code 493.xx. Patients were divided into 3 age groups: children (<18 years), younger adults (18-54 years), and older adults (≥55 years). The outcome measures were in-hospital all-cause mortality, near-fatal asthma-related events (noninvasive or mechanical ventilation), hospital charges, admission rates, and hospital length of stay. There were an estimated 1,813,000 visits annually for acute asthma from approximately 4,700 EDs. The estimated overall annual number of in-hospital asthma-related deaths was 1,144 (0.06%); 101 died in the ED, and 1,043 died as inpatients. By age group, there were 37 asthma-related deaths per year in children, 204 in younger adults, and 903 in older adults. Compared with younger adults, older adults had higher mortality, had higher rates of near-fatal asthma-related events, had higher hospital charges, were more likely to be hospitalized, and had a longer hospital length of stay (P < .001 for all). After adjusting for comorbidities, older asthmatic patients had a 5-fold increased risk of overall mortality (adjusted odds ratio, 5.2; 95% CI, 4.0-6.9), compared with younger adults. Older adults with acute asthma have a substantial burden of morbidity and mortality. With the US population aging, there is an urgent need for targeted interventions for this high-risk population.


Competitive inhibition of electron donation to photosystem 1 by metal-substituted plastocyanin.
The electron transfer from wild-type spinach plastocyanin (Pc) to photosystem 1 has been studied by flash-induced absorption changes at 830 nm. The decay kinetics of photo-oxidized P700 are drastically slower in the presence of Ag(I)-substituted Pc, while addition of Zn(II)-substituted Pc has a weaker effect. The metal-substituted forms of Pc act as competitive inhibitors of the reaction between normal, Cu-containing, Pc and P700. The inhibition constants obtained from an analysis of the kinetic data were 30 and 410 microM for Ag(I)- and Zn(II)-substituted Pc, respectively. When the Gly8Asp mutant form of Pc was used instead of the wild-type form, the corresponding values were found to be 77 and 442 microM. If the Ag- and Zn-derivatives can be considered as structural mimics of reduced and oxidized CuPc, respectively, our results imply that there is a redox-induced decrease in the affinity between Pc and photosystem 1 that follows the electron donation to P700. Our data also imply that the Gly8Asp mutation can diminish the magnitude of this change. The findings reported here are consistent with a reaction mechanism where the electron transfer in the complex between Pc and photosystem 1 is assumed to be reversible.


Food waste: causes and economic losses estimation at household level in Pakistan.
Food waste is one of the major sustainability issues that need to be addressed due to its negative impacts on the economy, environment, and food security. To develop food waste reduction policies on regional and global level, it is mandatory to have a clear understanding of the various factors prompting food waste at household level and the extent of the economic losses incurred by food waste. Reducing food waste can decrease household expenditure on food, freeing resources for health, education, and well-being. The current study was aimed to (1) examine the food waste behavior of the respondents and to (2) determine the level of monetary losses from food waste. To address these objectives, a questionnaire survey and sample of food waste generated during 24 h were collected from 51 households in Tehsil Kahror Pakka, District Lodhran, Punjab, Pakistan. The survey focus was on levels of food waste and respondents' knowledge and behaviors about food waste. Economic estimation of food waste was also done. In the survey, respondents from both high- and low-income households revealed that their fruit and vegetables (31%; 32%) and peel and scrap (53%; 48%) losses were higher while egg losses (4%; 4%) were lower among various food waste categories. Wanting to eat fresh food and having no time to save food were the reasons for food waste. Monetary losses from food waste (US$ 12.8/Rs. 3677.01 per capita per annum) were higher in high-income households compared to low-income households.


Recent advances in arrhythmia therapy: treatment and prevention of atrial fibrillation.
Current therapy for atrial fibrillation is divided into rhythm control agents and rate control agents. Although class III antiarrhythmic agents are being used increasingly for both conversion of atrial fibrillation to sinus rhythm and prevention of recurrence, most pharmacological approaches under active investigation, including azimilide and dronedarone, are compounds with multiple electrophysiological actions. Based on the current knowledge of the mechanisms involved in atrial fibrillation initiation and maintenance, novel approaches targeting the intracellular calcium overload are being investigated.


Processing of adrenocorticotropin by two proteases in bovine intermediate lobe secretory vesicle membranes. A distinct acidic, tetrabasic residue-specific calcium-activated serine protease and a PC2-like enzyme.
Adrenocorticotropin (ACTH) is cleaved at the tetrabasic residue site, in pituitary intermediate lobe secretory vesicles, to yield ACTH1-17 and corticotropin-like intermediate lobe peptide (CLIP). ACTH1-17 is then converted to alpha-melanocyte-stimulating hormone (N-AcACTH1-13NH2) by first removing the Lys15-Lys16-Arg17 residues, followed by amidation of the COOH terminus and acetylation of the NH2 terminus. Bovine intermediate lobe secretory vesicle membranes were screened for proteolytic enzyme activity that will cleave the tetrabasic residues of ACTH. Two activities with pH optima of 5.0-6.0 and 7.5-8.0 were detected. The acidic, ACTH-converting enzyme cleaved ACTH1-39 at the tetrabasic residues between the Arg17-Arg18 bond to yield ACTH1-17 and CLIP, but did not cleave paired basic residues of pro-opiomelanocortin. This enzyme activity was characterized as a Ca(2+)-activated serine protease with unique specificity for the tetrabasic residues of ACTH1-39. The neutral activity preferentially generated ACTH1-17 and to a small extent ACTH1-16 from ACTH1-39 and ACTH1-24. This enzyme activity was Ca(2+)-dependent but was not inhibited by serine or aspartic protease inhibitors. The neutral activity was significantly immunodepleted by antiserum raised against bovine PC2/PC3, and together with specificity studies, suggests that the enzyme is a PC2-like serine protease. The pH optimum, distinct specificity for tetrabasic residues, and subcellular localization of the acidic ACTH-converting enzyme indicate a function of this enzyme in the in vivo conversion of ACTH1-39 to alpha-melanocyte-stimulating hormone in intermediate lobe secretory vesicles which have an acidic internal pH.


The effects of three selected endocrine disrupting chemicals on the fecundity of fruit fly, Drosophila melanogaster.
Bisphenol A (BPA), 4-nonylphenol (4-NP) and 4-tert-octylphenol (4-tert-OP) are the endocrine disrupting chemicals (EDCs) that has been shown to exert both toxic and biological effects on living organisms. The present study investigated effects of environmentally relevant concentrations of BPA, 4-NP and 4-tert-OP (0.1, 1 and 10 mg/L) on the fecundity of fruit fly Drosophila melanogaster. In the all exposure groups of BPA, 4-NP and 4-tert-OP, it was found a statistically significant decrease in mean fecundity as compared to the control groups (p < 0.05).


Importance of thymidine kinase activity for normal growth of lumpy skin disease virus (SA-Neethling).
In order to study the importance of an intact thymidine kinase (TK) gene for the vaccine strain of a southern African capripoxvirus, namely, lumpy skin disease virus (LSDV) (type SA-Neethling), a TK disruption recombinant was generated expressing the Escherichia coli beta-galactosidase (lacZ) reporter gene. A comparative growth study of the recombinant and wild-type (wt) LSDV in TK-positive primary and secondary cells and TK-negative secondary cells was performed. It was found that although recombinant and wt virus both grew in TK-positive cells without selection, the recombinant was unable to grow in TK-negative cells (with or without selection), indicating that TK activity is important, if not essential, for normal growth of LSDV.


Effects of substance P on sympathetic preganglionic neurones.
Antidromically identified sympathetic preganglionic neurones, located in the second thoracic segment of the rat spinal cord, were tested for their response to iontophoretically applied substance P. Substance P increased the firing rate of both 'spontaneously' active and glutamate-activated neurones. As substance P-like immunoreactivity is present in the intermediolateral cell column of the thoracic spinal cord, it is concluded that substance P may be an excitatory transmitter or modulator involved in mediating excitatory drive to sympathetic preganglionic neurones.


Malunion of the proximal humerus.
Malunion of a proximal humerus fracture is difficult to manage once bone union has been achieved in a wrong position. Malunion may be encountered after conservative treatment or internal fixation of fractures, and also around a joint prosthesis. The malunion can involve the greater and lesser tuberosities, humeral head, bicipital groove, or the entire epiphysis. The nature of the malunion must be precisely characterized. Malunion can affect bone structures and the articular surface; any resulting displacements must be carefully measured. Clinical assessments will help to evaluate the functional repercussions and determine the need for correction. Radiographic imaging and CT scan guide the treatment plan. Arthroscopic surgery (acromioplasty or tuberoplasty) can be used to treat biceps tenosynovitis or impingement syndrome in cases where full correction of the malunion is not required. Corrective surgery of a metaphyseal malunion is used to realign the proximal humeral into the proper position. Tuberosity osteotomy is the main predictor for a poor outcome following secondary arthroplasty.


Investigation of SARS-CoV-2 lineages and mutations circulating in a university-affiliated hospital in South Korea analyzed using Oxford Nanopore MinION sequencing.
Despite the introduction of vaccines, treatments, and massive diagnostic testing, the evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued to overcome barriers that had slowed its previous spread. As the virus evolves towards increasing fitness, it is critical to continue monitoring the occurrence of new mutations that could evade human efforts to control them. We performed whole-genome sequencing using Oxford Nanopore MinION sequencing on 58 SARS-CoV-2 isolates collected during the ongoing coronavirus disease 2019 pandemic at a tertiary hospital in South Korea and tracked the emergence of mutations responsible for massive spikes in South Korea. The differences among lineages were more pronounced in the spike gene, especially in the receptor-binding domain (RBD), than in other genes. Those RBD mutations could compromise neutralization by antibodies elicited by vaccination or previous infections. We also reported multiple incidences of Omicron variants carrying mutations that could impair the diagnostic sensitivity of reverse transcription-polymerase chain reaction-based testing. These results provide an understanding of the temporal changes of variants and mutations that have been circulating in South Korea and their potential impacts on antigenicity, therapeutics, and diagnostic escape of the virus. We also showed that the utilization of the nanopore sequencing platform and the ARTIC workf low can provide convenient and accurate SARS-CoV-2 genomic surveillance even at a single hospital.


[Contained rupture of the non-coronary sinus of Valsalva aneurysm into the right atrium (Sakakibara type IV) treated by surgery].
A 26-year-old woman of Cap Verdean origin was admitted to emergency unit with chest pain and dyspnea. Because of sinus tachycardia without any other electrocardiogram abnormalities, high NT-pro BNP level, and weakly positive cardiac troponin I and D-dimer levels, an aortic and pulmonary non ECG-gated CT-angiography was performed that excluded pulmonary embolism and aortic dissection. Transthoracic echocardiography (TTE) showed a contained rupture of the non-coronary sinus of Valsalva aneurysm sized 23 to 24mm into the right atrium. According to the high rupture risk, patient had been immediately transferred in a cardiologic surgical center where transesophageal echocardiography (TEE) and thoracic angiography ECG-gated Multiple Detector Computerized Tomography (ECG-gated MDCT) reinforced the diagnosis. Patient underwent surgical repair resection of the aneurysmal sac, which was described as "tissue paper thin" and at risk for impending rupture, without evidence of communication between the aorta and the right atrium. Anatomopathological examination described a thick sclerotic and oedematous aneurysm wall without inflammation, and bacteriological examination was negative. It is a rare case of contained rupture of the congenital non-coronary sinus of Valsalva aneurysm into the right atrium (Type IV of Sakakibara classification), with a high rupture risk. This case shows that the use ECG-gated-MDCT is more appropriate when aortic dissection is suspected, allowing a detailed analysis of aorta, especially the proximal portion which is more susceptible to motion artifacts.


Comprehensive analysis of elemental distribution in human skin using laser ablation inductively coupled plasma mass spectrometry.
Multiple chemical elements play roles in skin homeostasis. The distribution of elements in skin has been studied by X-ray microanalysis methods and fluorescence microscopy using chemical indicators, but the former requires complicated sample preparation steps, while the latter is limited by the availability of suitable chemical indicators. We applied laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) to measure the distributions of thirty-eight elements in human skin. Among the target elements, nine (calcium: 40 Ca, 44 Ca, zinc: 64 Zn, 66 Zn, phosphorus: 31 P, potassium: 39 K, sodium: 23 Na, sulfur: 34 S, copper: 63 Cu, magnesium: 24 Mg, and iron: 56 Fe) showed distribution patterns that were consistent with previous reports, and four others (iodine: 127 I, barium: 138 Ba, strontium: 88 Sr, and molybdenum: 95 Mo) were detected for the first time in human skin. The method described here requires only slicing into sections to prepare a sample for measurement, so the elemental distributions are minimally disturbed, and comprehensive information can be obtained rapidly. The method is expected to be useful for research in a variety of fields, including skin diseases, aging, and allergenicity.


Factors Associated with Depression in COPD: A Multicenter Study.
Depression is a prevalent comorbidity in COPD and has an impact on the prognosis of these patients, thereby making it important to study the factors associated with depression in patients with COPD. A multicenter, observational and cross-sectional study was conducted to study the factors associated with depression in patients with COPD measured by the hospital anxiety and depression (HAD) questionnaire. We analyzed anthropometric variables and the number of exacerbations in the previous year and calculated the 6-min walking test and the body mass index, airflow obstruction, dyspnea, and exercise (BODE) index. All the patients completed the quality of life EQ-5D and the LCADL physical activity questionnaires. The relationship of these variables with depression was evaluated with two multiple logistic regression models. One hundred fifteen patients were evaluated (93 % male) with a mean age of 66.9 years (SD 8.8) and a mean FEV1 % of 44.4 % (SD 15.7 %). 24.3 % presented symptoms of depression (HAD-D > 8). These latter patients had worse lung function, greater dyspnea, reduced exercise capacity, a higher score in the BODE index, poorer quality of life, reduced physical activity, and more exacerbations. In the first logistic regression model, quality of life and the BODE index were associated with depression (AUC: 0.84; 0.74-0.94). In the second model including the variables in the BODE index, quality of life and dyspnea measured with the MRC scale (AUC: 0.87; 0.79-0.95) were associated with depression. Nearly one-quarter of the patients with COPD in this study presented clinically significant depression associated with worse quality of life, reduced exercise capacity, greater dyspnea, and a higher score in the BODE index.


Human iPS Cell-derived Tissue Engineered Vascular Graft: Recent Advances and Future Directions.
Tissue engineered vascular grafts (TEVGs) generated from human primary cells represent a promising vascular interventional therapy. However, generation and application of these TEVGs may be significantly hindered by the limited accessibility, finite expandability, donor-donor functional variation and immune-incompatibility of primary seed cells from donors. Alternatively, human induced pluripotent stem cells (hiPSCs) offer an infinite source to obtain functional vascular cells in large quantity and comparable quality for TEVG construction. To date, TEVGs (hiPSC-TEVGs) with significant mechanical strength and implantability have been generated using hiPSC-derived seed cells. Despite being in its incipient stage, this emerging field of hiPSC-TEVG research has achieved significant progress and presented promising future potential. Meanwhile, a series of challenges pertaining hiPSC differentiation, vascular tissue engineering technologies and future production and application await to be addressed. Herein, we have composed this review to introduce progress in TEVG generation using hiPSCs, summarize the current major challenges, and encapsulate the future directions of research on hiPSC-based TEVGs. Graphical abstract.


Multidisciplinary management of Mirizzi syndrome with cholecystobiliary fistula: the value of minimally invasive endoscopic surgery.
Mirizzi syndrome, a rare complication of gallstones, is defined by obstruction of the main bile duct. This obstruction may worsen and thus result in cholecystobiliary fistula. Surgical management of Mirizzi syndrome is complicated by the presence of inflamed tissue around the hepatic pedicle, making it impossible to distinguish between the main bile duct and the gallbladder. The surgeon's first task is to perform subtotal cholecystotomy (from the fundus of the gallbladder to the neck) without trying to locate the cystic duct. In a second step, the gallstones are extracted and the main bile duct is then repaired. In most cases, a T-tube is used to drain the main bile duct, and abdominal drainage is left in place (in case a bile fistula forms). This study concluded that preoperative drainage of the main bile duct in the treatment of Mirizzi syndrome types II and III is feasible and might help to decrease the postoperative complication rate.


Anaerobic transformation of phenol to benzoate via para-carboxylation: use of fluorinated analogues to elucidate the mechanism of transformation.
Isomeric fluorophenols were used as phenol analogues to investigate the transformation of phenol to benzoate by an anaerobic, phenol-degrading consortium derived from freshwater sediment. Transformation of 2-fluorophenol and 3-fluorophenol led to the accumulation of fluorobenzoic acids. 2-Fluorophenol was transformed in the presence or absence of phenol, while 3-fluorophenol transformation was only observed in the presence of phenol. Identification of the resulting fluorobenzoate products as 3-fluorobenzoate and 2-fluorobenzoate isomers, respectively, together with the nontransformation of 4-fluorophenol indicated that the carboxyl group was introduced para to the phenolic hydroxyl group.


Discovery and optimization of 3-thiophenylcoumarins as novel agents against Parkinson's disease: Synthesis, in vitro and in vivo studies.
Monoamine oxidase B (MAO-B) inhibitors are still receiving great attention as promising therapeutic agents for central nervous system disorders. This study explores, for the first time, the potential of 3-thiophenylcoumarins as in vitro and in vivo agents against Parkinsońs disease. Twelve compounds were synthesized via Perkin-Oglialoro reaction, and in vitro evaluation of six hydroxylated molecules was performed. MAO-A and MAO-B inhibition, DPPH scavenging and inhibition of ROS formation, neurotoxicity on motor cortex neurons and neuroprotection against H2O2, were studied. In vivo effect on locomotor activity using the open field test was also evaluated for the best candidate [3-(4'-bromothiophen-2'-yl)-7-hydroxycoumarin, 5], a potent, selective and reversible MAO-B inhibitor (IC50 = 140 nM). This compound proved to have a slightly better in vivo profile than selegiline, one of the currently treatments for Parkinson's disease, in reserpinized mice pretreated with levodopa and benserazide. Results suggested that, comparing positions 7 and 8, substitution at position 7 of the coumarin scaffold is better for the enzymatic inhibition. However, the presence of a catechol at positions 7 and 8 exponentially increases the antioxidant potential and the neuroprotective properties. Finally, all the molecules present good theoretical physicochemical properties that make them excellent candidates for the optimization of a lead compound.


Stochastic aggregative responses and spatial patterns of parasitism in patchy host-parasitoid interactions.
Assuming random search by parasitoids within host-containing patches, and a constant search rate, current host-parasitoid models suggest that positive "searching time aggregation" by parasitoids in patches of high host density should tend to produce spatially density dependent parasitism at the patch level. However, these models view the aggregative response as a deterministic process, ignoring variability in searching time (T s) allocation among patches of equal host density, and it is not clear that stochastic analogues of these deterministic models would predict the same result.This question is examined by adding a stochastic aggregative response to the well-known "random parasitoid equation," the deterministic equation on which most existing models have been based. Simulations, based on data collected in an earlier laboratory study, indicate that this stochastic model generates very different relationships between parasitoid searching behavior and spatial patterns of parasitism than are predicted using the deterministic approach. The stochastic model suggests that "positive" aggregative responses, in which patches of high host density receive larger allocations of searching time (on the average) than patches containing lower densities, may fail to produce spatially density dependent parasitism at the patch level if searching time allocation is also more variable at the higher densities. Similarly, a "flat" response, in which mean searching times do not vary among patches of different host density, may lead to density dependent, density independent, or inversely density dependent parasitism, depending on the variance of the searching time values among patches at different density levels. The different predictions generated by the deterministic and stochastic models can be explained on purely mathematical grounds.When models are written in units of total foraging time (T TOT), different equations are usually required to describe the spatial features of host-parasitoid and predator-prey interactions. Because the model considered here is written in units of active searching time (T s) it should, in cases in which the underlying assumptions hold, be capable of describing these different interactions in the framework of a single ("unified") equation. This equation may also apply to some plant-herbivore systems and, to indicate its potential generality, might be referred to as a "random forager" equation.


A small family of sushi-class retrotransposon-derived genes in mammals and their relation to genomic imprinting.
Ty3/gypsy retrotransposons are rare in mammalian genomes despite their abundance in invertebrate and other vertebrate classes. Here we identify a family of nine conserved mammalian genes with homology to Ty3/gypsy retrotransposons but which have lost their ability to autonomously retrotranspose. Of these, five map to the X chromosome while the remaining four are autosomal. Comparative phylogenetic analyses show them to have strongest homology to the sushi-ichi element from Fugu rubripes. Two of the autosomal gene members, Peg10 and Rtl1, are known to be imprinted, being expressed from the paternally inherited chromosome homologue. This suggests, consistent with the host-parasite response theory of the evolution of the imprinting mechanism, that parental-origin specific epigenetic control may be mediated by genomic "parasitic" elements such as these. Alternatively, these elements may preferentially integrate into regions that are differentially modified on the two homologous chromosomes such as imprinted domains and the X chromosome and acquire monoallelic expression. We assess the imprinting status of the remaining autosomal members of this family and show them to be biallelically expressed in embryo and placenta. Furthermore, the methylation status of Rtl1 was assayed throughout development and was found to resemble that of actively, silenced repetitive elements rather than imprinted sequences. This indicates that the ability to undergo genomic imprinting is not an inherent property of all members of this family of retroelements. Nonetheless, the conservation but functional divergence between the different members suggests that they have undergone positive selection and acquired distinct endogenous functions within their mammalian hosts.


Adaptation to slope in locomotor-trained spinal cats with intact and self-reinnervated lateral gastrocnemius and soleus muscles.
Sensorimotor training providing motion-dependent somatosensory feedback to spinal locomotor networks restores treadmill weight-bearing stepping on flat surfaces in spinal cats. In this study, we examined if locomotor ability on flat surfaces transfers to sloped surfaces and the contribution of length-dependent sensory feedback from lateral gastrocnemius (LG) and soleus (Sol) to locomotor recovery after spinal transection and locomotor training. We compared kinematics and muscle activity at different slopes (±10° and ±25°) in spinalized cats (n = 8) trained to walk on a flat treadmill. Half of those animals had their right hindlimb LG/Sol nerve cut and reattached before spinal transection and locomotor training, a procedure called muscle self-reinnervation that leads to elimination of autogenic monosynaptic length feedback in spinally intact animals. All spinal animals trained on a flat surface were able to walk on slopes with minimal differences in walking kinematics and muscle activity between animals with/without LG/Sol self-reinnervation. We found minimal changes in kinematics and muscle activity at lower slopes (±10°), indicating that walking patterns obtained on flat surfaces are robust enough to accommodate low slopes. Contrary to results in spinal intact animals, force responses to muscle stretch largely returned in both SELF-REINNERVATED muscles for the trained spinalized animals. Overall, our results indicate that the locomotor patterns acquired with training on a level surface transfer to walking on low slopes and that spinalization may allow the recovery of autogenic monosynaptic length feedback following muscle self-reinnervation.NEW & NOTEWORTHY Spinal locomotor networks locomotor trained on a flat surface can adapt the locomotor output to slope walking, up to ±25° of slope, even with total absence of supraspinal CONTROL. Autogenic length feedback (stretch reflex) shows signs of recovery in spinalized animals, contrary to results in spinally intact animals.


High sensitivity C-reactive protein: a novel predictor for recurrence of atrial fibrillation after successful cardioversion.
We sought to test the hypothesis that C-reactive protein (CRP) can predict the recurrence of atrial fibrillation (AF) after successful electrical cardioversion (CV). In patients with AF, CRP levels are predictive of immediate failure of CV. We prospectively measured high-sensitivity CRP in 67 patients with AF or atrial flutter who underwent successful electrical CV. At one-month follow-up, 22 patients (33%) had recurrence of their arrhythmia. Arrhythmia recurrence was associated with significantly higher pre-CV CRP levels (odds ratio [OR] 1.84; 95% confidence interval [CI] 1.14 to 2.98; p = 0.013) even after adjusting for age (OR 2.22; 95% CI 1.25 to 3.93; p = 0.006), for gender (OR 1.89; 95% CI 1.16 to 3.09; p = 0.011), or duration of arrhythmia (OR 1.86; 95% CI 1.13 to 3.07; p = 0.015). On multivariate analysis, CRP was the only independent predictor of arrhythmia recurrence (OR 2.19; 95% CI 1.05 to 4.55; p = 0.036). Our data suggest that high levels of CRP are associated with an increased risk of recurrence of AF within one month. These data support the hypothesis that anti-inflammatory interventions may help in maintenance of normal sinus rhythm after CV. These data also may have implications for the identification of patients who are most likely to experience substantial benefit from CV therapy for AF.


Classification of benign endometrial glandular cells in cervical smears from postmenopausal women.
The Bethesda System recommends reporting benign endometrial cells in cervical smears from postmenopausal (PMP) women as a glandular cell abnormality. However, PMP women on hormone replacement therapy (HRT) sometimes may experience endometrial shedding. The significance of such a finding has not been investigated in detail. The authors evaluated 85 PMP women with cervical smears that contained benign endometrial glandular cells. Clinical information, including vaginal bleeding and the use of HRT or tamoxifen, was recorded, and follow-up was obtained. Thirty-three PMP women were not on HRT, and 11 women were symptomatic. Twenty women underwent endometrial biopsy: Two symptomatic patients had endometrial adenocarcinoma, and 3 symptomatic patients and 1 asymptomatic patient had endometrial polyps. The frequency of abnormal findings was 18%. Forty-seven PMP women received HRT; 15 were symptomatic. Twenty-two patients underwent endometrial biopsy: 1 symptomatic patient had cystic hyperplasia, and 2 symptomatic patients and 1 asymptomatic patient had an endometrial polyp. The frequency of abnormal findings was 8.5%. No one type of HRT was correlated with specific findings. Five PMP women were on tamoxifen, and two of them were symptomatic. Four patients underwent endometrial sampling: Two of them had an endometrial polyp, which was symptomatic in one patient. These data confirm that benign endometrial glandular cells in cervical smears from PMP women may indicate endometrial pathology, especially if vaginal bleeding is present. Although atypical endometrial hyperplasia or carcinoma was not identified in the group of PMP women on HRT, endometrial abnormalities of a lesser degree were present in 8.5% of patients. Thus, the authors favor continued classification of benign endometrial glandular cells in cervical smears of PMP women, whether or not they are on HRT, as a glandular cell abnormality.


Crisis placement.
This article reviews some factors that influence the crisis placements of high-risk children, and describes an intervention designed to ensure safety and permanence for children, by supporting biological and kinship families, preventing unwarranted family disruption, and reducing the need for multiple placements. Some of the barriers to thoughtful risk-taking and decision-making in child protective service systems are discussed and the importance of collaboration among child protection, health, and mental health professionals is emphasized.


Cardiac arrhythmias and sudden unexpected death in epilepsy: Results of long-term monitoring.
Cardiac rhythm and conduction disorders are common in patients with epilepsy and are presumably one of the leading causes of sudden unexpected death. There are only a few published reports on ictal cardiac arrhythmias detected by continuous monitoring, and the majority had a small sample size. The aim of this study was to evaluate the frequency and type of cardiac arrhythmias recorded by an implantable loop recorder in patients with drug-resistant epilepsy. We implanted a subcutaneous loop recorder to 193 patients with drug-resistant epilepsy. Automatic triggers to initiate cardiac rhythm recording were cardiac pauses of >3 seconds and any episodes of bradycardia (≤45 beats/min) or tachycardia (≥150 beats/min). Patients/relatives were instructed to begin peri-ictal rhythm recording by using an external activator device. The follow-up duration was 36 months, with scheduled follow-up visits every 3 months. A total of 6494 electrocardiogram traces were recorded during the median follow-up of 36 months (interquartile range 3-36 months). Ictal heart rhythm and rate changes were detected in 143 patients (74%). The most common finding was ictal sinus tachycardia (66.8%). Sinus bradycardia was observed in 13 patients (6.7%). Three patients had clinically relevant cardiac pauses of >6 seconds, requiring permanent pacemaker implantation. Five patients (2.6%) died suddenly. Ictal heart rhythm and rate changes occur in most of the patients with drug-resistant epilepsy. Clinically relevant cardiac events, related to ictal and postictal periods, are rare. No potentially malignant arrhythmias were detected in patients who died suddenly during the preceding follow-up period.


Inflammation and fibrosis in Crohn's disease: location-matched histological correlation of small bowel ultrasound features.
To evaluate the utility of mural and extramural sonographic features of Crohn's Disease as potential imaging biomarkers of inflammation and fibrosis against whole-mount histological sections. Twelve Crohn's disease patients (Mean age 35(25-69), 7 males) underwent small bowel ultrasound prior to small bowel resection. Two radiologists in consensus graded multiple parameters including mural, mucosal and submucosal thickness, submucosal/mesenteric echogenicity and clarity and mural Doppler signal in 50 selected bowel cross-sections. Matching with histological sampling sites was facilitated via scanning of the resected specimen. A histopathologist scored acute and chronic inflammation, and fibrosis (using histological scoring systems) following analysis of whole mount block sections. The association between sonographic observations and histopathological scores was examined via univariable and multivariable analysis. In univariate analyses, bowel wall thickness (regression co-efficient and 95% CI 0.8 (0.3, 1.3) p = 0.001), mesenteric fat echogenicity (8.7(3.0, 14.5) p = 0.005), submucosal layer thickness (7.4(1.2, 13.5) p = 0.02), submucosal layer clarity (4.4(0.6, 8.2) p = 0.02) and mucosal layer thickness (4.6(1.8, 7.4) p = 0.001) were all significantly associated with acute inflammation. Mesenteric fat echogenicity (674(8.67, 52404) p = 0.009), submucosal layer thickness (79.9(2.16, 2951) p = 0.02) and mucosal layer thickness (13.6(1.54, 121) p = 0.02) were significantly associated with chronic inflammation. Submucosal layer echogenicity (p = 0.03), clarity (25.0(1.76, 356) p = 0.02) and mucosal layer thickness (53.8(3.19, 908) p = 0.006) were significantly associated with fibrosis. In multivariate analyses, wall and mucosal thickness remained significantly associated with acute inflammation (p = 0.02), mesenteric fat echogenicity with chronic inflammation (p = 0.009) and mucosal thickness (p = 0.006) with fibrosis. Multiple sonographic parameters are associated with histological phenotypes in Crohn's disease although there is overlap between ultrasonic stigmata of acute inflammation, chronic inflammation and fibrosis.


Transient coordinated activity within the developing brain's default network.
The concept of a brain default network postulates that specific brain regions are more active when a person is engaged in introspective mental activity. Transient functional coordination between groups of neurons is thought to be necessary for information processing. Since children develop introspection as they mature, regions of the default network may establish increasing functional coordination with age, resulting in fewer fluctuations in synchronization patterns. We investigated the transient coordinated activity in regions of the default network in seventeen children aged 11 months to 17 years of age using EEG recordings while subjects were resting quietly with eyes closed. The temporal and spatial fluctuations in the phase synchrony patterns were estimated across sites associated with the default network pattern and compared to other regions. Lower variability of the spatio-temporal patterns of phase synchronization associated with the default network was observed in the older group as compared to the younger group. This indicates that functional coordination increases among regions of the default network as children develop.


Unexpectedly high levels of antimony (III) in the pentavalent antimonial drug Glucantime: insights from a new voltammetric approach.
Glucantime, a pentavalent antimonial drug, is commonly used for the treatment of leishmaniasis but the presence of residual trivalent antimony, Sb(III), is thought to be responsible for toxic side-effects observed in patients. Numerous analytical studies have focused on determining Sb(III) concentrations in Glucantime but without reaching a consensus: results span over 3 orders of magnitude. In this study, we present a detailed new analytical approach showing that: (1) Sb(III) levels are much higher than previously reported and represent more than 30% of total Sb; (2) determination of Sb(III) concentrations in acidic conditions is hampered by fast oxidation rates. This latter point explains the large variations in previously reported results of Sb(III) concentrations in Glucantime. Measurements were made here at a vibrated gold microwire electrode by stripping voltammetry enabling measurement of Sb(III) in acidic, neutral or alkaline conditions. The developed methods are sensitive (e.g., detection limits of 19 pM for 120 s deposition at pH 4.5), stable (<6%, N = 100), precise (5%, N = 5) and robust (same electrode used for weeks) at all pH values. In diluted solutions of Glucantime, Sb(III) levels were strongly dependent both on pH and ionic strength. At pH < 3, Sb(III) is oxidized with oxidation rates that increase as pH is decreased. At high pH, Sb(III) forms electro-inactive complexes. Highest Sb(III) levels were detected at pH ~3 and at low ionic strength. The presence of several Sb(III) and Sb(V) species was demonstrated by different reduction waves obtained by stripping scanned voltammetry. As an implication of these unexpectedly high Sb(III) concentrations, an alternative model can be proposed for the mode of action of pentavalent antimonials against leishmaniasis, in which antimony complexes may act as molecular carrier of Sb(III) and release it specifically in the acidic intracellular compartment where the Leishmania parasites reside.


DSCAM-AS1 promotes cervical carcinoma cell proliferation and invasion via sponging miR-338-3p.
Deregulated lncRNA DSCAM-AS1 expression was found in several tumors. However, mechanism and functional role of DSCAM-AS1 in cervical carcinoma remain unknown. DSCAM-AS1 was detected in cervical carcinoma specimens and cells by RT-qPCR. CCK-8, Matrigel transwell, and flow cytometry were conducted to determine cell functions. In this research, we firstly we explored DSCAM-AS1 expression in cervical carcinoma cells and specimens. We revealed that DSCAM-AS1 was upregulated in cervical carcinoma lines (C4-1, Caski, Hela, and Siha) compared to GH329 cells. DSCAM-AS1 was upregulated in cervical carcinoma specimens compared to control no-tumor specimens. Overexpression of DSCAM-AS1 induced cervical carcinoma cell growth and cycle. Moreover, our data revealed that miR-338-3p expression was downregulated in cervical carcinoma cells and specimens. There was a negative correlation between miR-338-3p expression and DSCAM-AS1 expression in cervical carcinoma specimens. Elevated expression of miR-338-3p decreased cervical carcinoma cell growth and cycle and invasion. Furthermore, luciferase reporter analysis revealed that miR-338-3p overexpression suppressed luciferase activity of WT-DSCAM-AS1 vector but not the mut-DSCAM-AS1. Ectopic expression of DSCAM-AS1 decreased miR-338-3p expression in the Siha cell. Overexpression of DSCAM-AS1 promoted cervical carcinoma cell growth and cycle via regulating miR-338-3p. These results suggested that DSCAM-AS1 functions as one oncogene through sponging miR-338-3p in cervical carcinoma.


Analysis of intracranial hemorrhage grade in preterm singleton pregnancies delivered vaginally or by cesarean section.
Preterm birth is the leading cause of neonatal mortality. Periventricular hemorrhage-intraventricular hemorrhage (PVH-IVH) remains a significant cause of both morbidity and mortality in infants prematurely born. The aim of the study was to evaluate the perinatal outcome regarding IVH of premature babies according to the mode of delivery. A total of 126 women in preterm singleton pregnancies with vertex presentation and 126 neonates weighted from 750 g to 1,500 g at birth were enrolled. The outcomes of 64 neonates born vaginally were compared to 62 neonates born by cesarean section. There was no significant difference in the incidence of IVH among both groups. Our data is consistent with the hypothesis that the mode of delivery does not influence IVH and consenquently perinatal outcome in preterm neonates.


Complex formed by complementary RNA stem-loops and its stabilization by a protein: function of CoIE1 Rom protein.
A small plasmid-specified RNA (RNA I) inhibits formation of the RNA primer for CoIE1 DNA replication by binding to its precursor (RNA II). Binding is modulated by the plasmid-specified Rom protein. Both in the presence and absence of Rom, binding starts with interaction between loops of RNAs. To understand the mechanism of binding, we examined the interactions of pairs of single stem-loops that are complementary fragments of RNA I and RNA II. We found that these complementary single stem-loops bind to each other at their loops, forming an RNAase V1-sensitive structure. Rom protects the complex from cleavage and from alkylation of phosphate groups by ethyinitrosourea. A single dimer of Rom binds to the complex by recognizing the structure rather than its exact nucleotide sequence. Rom enhances complex formation by decreasing the rate of dissociation of the complex. Structures of RNA complexes formed in the presence and absence of Rom are proposed.


Stable isotope ratio measurements of Cu and Zn in mineral dust (bulk and size fractions) from the Taklimakan Desert and the Sahel and in aerosols from the eastern tropical North Atlantic Ocean.
Accurate characterization of the stable isotope composition of Cu and Zn in major global mineral dust sources and in aerosols is central to the application of these isotope systems to the studies of global geochemical processes and cycles. We test here for the first time Cu and Zn isotope ratios within a well-defined source-receptor setting on the continent-ocean interface and determine the isotope composition of (i) bulk surface soil dust samples from the Sahel region, (ii) individual size fractions of surface dust samples from the Taklimakan Desert, and (iii) aerosols collected in the equatorial eastern North Atlantic region. This is achieved reducing the blank contribution during the ion exchange step using small resin and acid volumes and using a second ion exchange passage to purify the Cu fraction. We find no significant correlation between size fractions and isotope ratios in the two samples analyzed from the Taklimakan Desert. Mass balance calculations suggest that isotope ratios of bulk samples are within the analytical precision of the <4 μm size fraction and can be used to characterize atmospheric long range transport of Cu and Zn in mineral dust from the Taklimakan Desert. The <1 µm size fractions of two aerosol samples collected over the equatorial eastern North Atlantic region have Cu and Zn isotope ratios that are different to Sahel surface soil dust suggesting important non-crustal sources, in line with calculated enrichment factors, and possibly of anthropogenic origin. Using previously reported δ(66)Zn values for anthropogenic emission from Europe, preliminary calculations suggest that up to 55% of Zn arriving at the sampling points in the equatorial eastern North Atlantic region could be of anthropogenic origin.


Optical biosensors for environmental monitoring: Recent advances and future perspectives in bacterial detection.
The environmental contamination due to bacterial proliferation vs their identification is the major deciding factor in the spread of diseases leading to pandemics. The advent of drug-resistant pathogenic contaminants in our environment has further added to the load of complications associated with their diagnosis and treatment. Obstructing the spread of such infections, prioritizes the expansion of sensor-based diagnostics, effectuating, a sturdy detection of disease-causing microbes, contaminating our surroundings in shortest possible time, with minimal expenditure. Among many sensors known, optical biosensors promote the recognition of pathogens befouling the environment through a comparatively intuitive, brisk, portable, multitudinous, and thrifty approach. This article reviews the recent progresses in optical biosensor-based systems for effective environmental monitoring. The technical and methodological perspectives of fundamental optical-sensing platforms are reviewed, combined with the pros and cons of every procedure. Eventually, the obstacles lying in the path of development of an effective optical biosensor device for bio-monitoring and its future perspectives are highlighted in the present work.


A label-free fluorescence strategy for selective detection of nicotinamide adenine dinucleotide based on a dumbbell-like probe with low background noise.
In this work we developed a novel label-free fluorescence sensing approach for the detection of nicotinamide adenine dinucleotide (NAD(+)) based on a dumbbell-like DNA probe designed for both ligation reaction and digestion reaction with low background noise. SYBR Green I (SG I), a double-helix dye, was chosen as the readout fluorescence signal. In the absence of NAD(+), the ligation reaction did not occur, but the probe was digested to mononucleotides after the addition of exonuclease I (Exo I) and exonuclease I (Exo III), resulting in a weak fluorescence intensity due to the weak interaction between SG I and mononucleotides. In the presence of NAD(+), the DNA probe was ligated by Escherichia coli DNA ligase, blocking the digestion by Exo I and Exo III. As a result, SG I was intercalated into the stem part of the DNA dumbbell probe and fluorescence enhancement was achieved. This method was simple in design, fast to operate, with good sensitivity and selectivity which could discriminate NAD(+) from its analogs.


Leptin/HER2 crosstalk in breast cancer: in vitro study and preliminary in vivo analysis.
Obesity in postmenopausal women is associated with increased breast cancer risk, development of more aggressive tumors and resistance to certain anti-breast cancer treatments. Some of these effects might be mediated by obesity hormone leptin, acting independently or modulating other signaling pathways. Here we focused on the link between leptin and HER2. We tested if HER2 and the leptin receptor (ObR) can be coexpressed in breast cancer cell models, whether these two receptors can physically interact, and whether leptin can transactivate HER2. Next, we studied if leptin/ObR can coexist with HER2 in breast cancer tissues, and if presence of these two systems correlates with specific clinicopathological features. Expression of ObR, HER2, phospho-HER2 was assessed by immunoblotting. Physical interactions between ObR and HER2 were probed by immunoprecipitation and fluorescent immunostaining. Expression of leptin and ObR in breast cancer tissues was detected by immunohistochemistry (IHC). Associations among markers studied by IHC were evaluated using Fisher's exact test for count data. HER2 and ObR were coexpressed in all studied breast cancer cell lines. In MCF-7 cells, HER2 physically interacted with ObR and leptin treatment increased HER2 phosphorylation on Tyr 1248. In 59 breast cancers, the presence of leptin was correlated with ObR (the overall association was about 93%). This result was confirmed both in HER2-positive and in HER2-negative subgroups. The expression of leptin or ObR was numerically more frequent in larger (> 10 mm) tumors. Coexpression of HER2 and the leptin/ObR system might contribute to enhanced HER2 activity and reduced sensitivity to anti-HER2 treatments.


Mediation of bradykinin-induced contraction in canine veins via thromboxane/prostaglandin endoperoxide receptor activation.
1. Canine jugular and femoral veins were studied to determine the possible importance of thromboxane (TXA2) and prostaglandin endoperoxides (prostaglandin H2, PGH2) in mediating bradykinin(BK)-induced contraction. 2. Isolated vein rings incubated in modified Krebs solution contracted to TXA2/PGH2 analogs SQ26655 and U44069 with potency of contraction exceeding that for BK. The potency ranking for both veins was SQ26655 greater than U44069 greater than BK greater than PGF2 alpha greater than TXB2 much greater than PGD2. 3. The cyclo-oxygenase inhibitors indomethacin (3 x 10(-7) M) and flufenamic acid (10(-5) M) reduced BK contractions without affecting those induced by noradrenaline (NA). 4. TXA2/PGH2 receptor antagonists SQ29548 (10(-8) M) and BM13177 (10(-6) M) strongly inhibited BK-induced tension. The action of antagonists was reversible with negligible influence on NA-elicited contraction. Selective removal of endothelium had no effect on BK-induced contraction or the action of the antagonists. 5. The thromboxane synthase inhibitors dazoxiben (10(-4) M) and CGS 12970 (10(-5) M) had no significant inhibitory effect on BK-induced tension. 6. These results suggest that in canine jugular and femoral vein, the action of BK is largely dependent upon stimulation of the cyclo-oxygenase pathway to produce PGH2 and possibly TXA2, which can activate a smooth muscle TXA2/PGH2 receptor to elicit vasoconstriction.


Guidelines set new benchmark for emergency care of children.
This spring, the American College of Emergency Physicians and the American Academy of Pediatrics issued joint guidelines on providing optimal care to children who visit emergency departments--more than 20 million visits annually. The guidelines raise the bar on pediatric emergency care and offer new benchmarks for EDs.


Alternaria alternata (SDHY01/02), a fungus associated with Lamellodysidea herbacea: its anticancer potential and responsible constituent(s).
One of the biggest global causes of death is cancer. The side effects of currently available therapies have triggered the search for new drugs. The marine environment, with its vast biodiversity, including sponges, is a rich source of natural products with immense pharmaceutical potential. The aim of the study was to analyze the microbes associated with the marine sponge, Lamellodysidea herbacea, and explore them as resources for anticancer ability. This study includes the isolation of fungi from L. herbacea, and their evaluation for cytotoxic potential against human cancer cell lines such as A-549 (lung), HCT-116 (colorectal carcinoma), HT-1080 (Fibrosarcoma), and PC-3 (prostate) using MTT assay. This revealed that fifteen extracts showed significant anticancer ability (IC50 ≤ 20 µg/mL), at least against one of the cell lines. Three extracts, SPG12, SPG19, and SDHY 01/02, were found significant in terms of anticancer activity, at least against three to four cell lines (IC50 values ≤ 20 µg/mL). The fungus SDHY01/02 was identified by sequencing the internal transcribed spacer (ITS) region as Alternaria alternata. Its extract showed IC50 values < 10 µg/mL against all the tested cell lines and was further analysed through light and fluorescence microscopy. The extract of SDHY01/02 was active (lowest IC50 4.27 µg/mL) against A549 cells in a dose-dependent manner and caused apoptotic cell death. Further, the extract was fractionated and analyzed the constituents by GC-MS (Gas Chromatography-Mass Spectrometry). Di-ethyl ether fraction revealed the constituents (having anticancer activity) such pyrrolo[1,2-a] pyrazine-1,4-dione, hexahydro-3-(2-methyl propyl); 4,5,6,7-tetrahydro-benzo[C]rhiophene-1-carboxylic acid cyclopropylamide; 17-pentatriacontene; 9,12-octadecadienoic acid (Z, Z)-, methyl ester; while DCM fraction contained Oleic acid, eicosyl ester. This is the first report of A. alternata with anticancer potential that has been isolated from the sponge L. herbacea, as far as we are aware.This A. alternata can be exploited to get anticancer molecule(s) in the future.


Immobilization of rhodopsin on a self-assembled multilayer and its specific detection by electrochemical impedance spectroscopy.
Rhodopsin, the G protein-coupled receptor (GPCR) which mediates the sense of vision, was prepared from calf eyes and used as receptor enriched membrane fraction. In this study it was immobilized onto gold electrode by two different techniques: Langmuir-Blodgett (LB) and a strategy based on a self-assembled multilayer. We demonstrated that Langmuir and LB films of rhodopsin are not stable. Thus, in this study a new protein multilayer was prepared on gold electrode by building up layer-by-layer a self-assembled multilayer. It is composed of a mixed self-assembled monolayer formed by MHDA and biotinyl-PE, followed by a biotin-avidin system which allows binding of biotinylated antibody specific to rhodopsin. The immobilization of rhodopsin in membrane fraction, by the specific antibody bound previously on self-assembled multilayer, was monitored with electrochemical impedance spectroscopy (EIS). In addition, the specificity and sensitivity of this self-assembled multilayer system to the presence of rhodopsin were investigated. No effect was observed when the system was in contact with olfactory receptor I7 in membrane fraction used for control measurements. All these results demonstrate that rhodopsin can be immobilized efficiently, specifically, quantitatively and stably on gold electrode through the self-assembled multilayer.


Fine-needle aspiration cytology of histiocytosis X: a case report.
The cytologic features of a case of histiocytosis X diagnosed by fine-needle aspiration biopsy of a right cervical lymph node in a 15-mo-old girl are reported. Characteristic reticuloendothelial cells with abundant cytoplasm and grooved nuclei were observed. Electron microscopy of the aspiration-derived specimen revealed Birbeck granules. The cytologic pattern and electron microscopic demonstration of Birbeck granules allowed definite diagnosis of lymph node involvement by histiocytosis X, negating the need for open biopsy. The cytologic differential diagnosis and current diagnostic criteria for histiocytosis X are discussed.


[Mal perforans and spinal dysraphia and lumbar stenosis syndromes].
The mal perforans is a chronic ulcer that is the result of pressure over anesthetic zones. This is a review of two neurological syndromes, the spinal dysraphism and the lumbar stenosis syndrome, in which the mal perforans can appears as a complication.


Olfactory deficits in HIV-infected patients with and without AIDS dementia complex.
The aim of the present study was to examine the effect of HIV infection on odour memory. Recognition and identification olfactory tests were administered to six groups of patients defined according to a decrease in cellular immunity: asymptomatic HIV seropositive (HIV+), symptomatic HIV+, HIV+ AIDS, and three groups with a mild, moderate, and severe degree of dementia (AIDS dementia complex [ADC]). Consistent with the literature, the general results show that HIV infection is associated with a decrease in olfactory ability. In addition, a polynomial linear trend analysis indicates a constant decrease in performance from the first to the sixth group of patients, related to the number of CD4 T lymphocytes circulating and to the severity of the pathology. An interesting result regards the drop in performance exhibited by ADC patients on the identification task. Reasonably, such an effect is not attributable to a decline in olfactory ability only, bit rather to a severe semantic memory deficit. It follows that the two tasks used here can be useful clinical supports to discriminate between the mental operations involved in a low cognitive demand task (recognition) and in a high cognitive demand task (identification).


[Quinoline derivative PQ1 combined with cisplatin promotes the proliferation and gap junction communication of prostate cancer PC3 cells].
To investigate the effects of the quinoline derivative PQ1 combined with cisplatin on the proliferation and gap junction communication of prostate cancer PC3 cells. We cultured in vitro prostate cancer PC3 cells and divided them into DMSO blank control, cisplatin control, and cisplatin (10 mg/ml) plus PQ1 (1, 2, 5, 10, and 15 μmol/L) groups. We measured the proliferation of the prostate cancer PC3 cells, determined the expressions of the connexin 43 (Cx43) mRNA and protein by RT-PCR and Western blot, and compared the indexes among different groups. Cisplatin combined with PQl at 1 - 10 μmol/L significantly inhibited the proliferation of the PC3 cells and the inhibition rate rose in a concentration- and time-dependent manner, from (48.72 ± 0.98)% vs (50.33 ± 0.62)% at 0 μmol/L to (77.38 ± 1.12)% vs (83.50 ± 1.05)% at 15 μmol/L at 24 and 48 hours (P < 0.05). Compared with the cisplatin control, cisplatin combined with PQ1 at 1, 2, 5, 10, and 15 μmol/L increased the expression of Cx43 mRNA from 0.379 ± 0.113 to 0.669 ± 0.031, 0.831 ± 0. 127, 0.769 ± 0.100, 0.532 ± 0.086, and 0.475 ± 0.134, respectively (P < 0.05), and cisplatin combined with PQ1 at 1, 2, 5, and 10 μmol/L elevated that of Cx43 protein from 0.138 ± 0.146 to 0.263 ± 0.111, 0.306 ± 0.152, 0.415 ± 0.280, and 0.643 ± 0.310, respectively (P < 0.05). The quinoline derivative PQ1 can promote the gap junction communication of prostate cancer PC3 cells and enhance the killing effect of cisplatin on PC3 cells by upregulating the expressions of Cx43 mRNA and protein.


Neutrophil elastase and cathepsin G: structure, function, and biological control.
When neutrophils invade inflamed areas of the body to remove either dead or foreign components they inadvertently release potent enzymes which can, if not properly controlled, cause severe damage to healthy tissue. This can lead to a myriad of diseases including emphysema, rheumatoid arthritis, and glomuerlopnephritis, all of which are really problems of abnormal connective tissue turnover due to uncontrolled protelysis by neutrophil elastase and cathepsin G. An important step in elucidating the functions of both elastase and cathepsin G has been made by virtue of the fact that the amino acid sequence of each has been determined. Furthermore, the crystal structure of one, neutrophil elastase, is now understood. With this knowledge in mind and with the potential for a similar understanding of the mechanism of action of cathepsin G, it should soon be possible to produce synthetic inhibitors of each enzyme which can act as adjunct inhibitors to those naturally circulating in the blood or present in other tissues. As a result there is great hope for reducing the severity of injury produced by these enzymes and, therefore, in decreasing the risk for development of the debilitating diseases associated with abnormal proteolysis by neutrophil proteinases.


[Early gastric carcinoma. 20 cases. Radioclinical, endoscopic and histopathological study (author's transl)].
The authors report twenty cases of early gastric carcinoma: superficial and with limited infiltration. The histological appearances varied, related to the macroscopic type of the tumour: protuberant, ulcerated, flat. The slightest clinical symptoms justify the most careful radiological study. Protuberant types result in a filling defect. Ulcerated types have a characteristic appearance of superficial ulcer, the folds involved being nodular or widely spread. Deeper regressive ulcerations are sometimes seen in association. Flat forms after the folds of a localised area of mucosa. The differential diagnosis is difficult. It is particularly important to eliminate the possibility of a benign ulcer, polypoid gastritis, lymphoid superficial ulcer, atrophic gastritis, well healed benign ulcer. Combined radiological and endoscopic studies are essential at all stages.


Assessment of hepatic metabolism-dependent nephrotoxicity on an organs-on-a-chip microdevice.
Drug-induced nephrotoxicity is one of the most frequent adverse events in pharmacotherapy. It has resulted in numerous clinical trial failures and high drug development costs. The predictive capabilities of existing in vitro models are limited by their inability to recapitulate the complex process of drug metabolism at the multi-organ level in vivo. We present a novel integrated liver-kidney chip that allows the evaluation of drug-induced nephrotoxicity following liver metabolism in vitro. The liver-kidney chip consists of two polydimethylsiloxane layers with compartmentalized micro-channels separated by a porous membrane. Hepatic and renal cells were co-cultured in separate micro-chambers on a single chip. Ifosfamide and verapamil were used as model drugs, and their metabolites produced by hepatic metabolism were identified using mass spectrometry, respectively. The metabolites triggered significantly distinct nephrotoxic effects as assessed by cell viability, lactate dehydrogenase leakage and permeability of renal cells. This in vitro liver-kidney model facilitates the characterization of drug metabolism in the liver as well as the assessment of subsequent nephrotoxicity in a single assay. Obviously, this multi-organ platform is simple and scalable, and maybe widely applicable to the evaluation of drug metabolism and safety during the early phases of drug development.


Consequences of the evolution of the GABA(A) receptor gene family.
1. This paper reviews the evolution of the family of genes present in mammals and other vertebrates that encode gamma-aminobutyric acid (GABA) type A (GABA(A)) receptors, which are the major inhibitory neurotransmitter receptors in the central nervous system (CNS). In mammals, 16 different polypeptides (alpha1-alpha6, beta1-beta3, gamma1-gamma3, delta, epsilon, pi, and theta) have been identified, using recombinant DNA techniques, each of which is encoded by a distinct gene. The products of these genes assemble in diverse combinations to form a variety of receptor subtypes that have different sensitivities to a number of clinically relevant compounds, such as the benzodiazepines (BZs). 2. Based on a number of chromosomal mapping techniques, the majority of the GABA(A) receptor genes have been localized, in man, in four clusters on chromosomes 4, 5, 15, and the X. Furthermore, the genes that are present within these clusters have a conserved transcriptional orientation. It has, therefore, been proposed that the clusters arose largely as a consequence of two whole-genome doublings that occurred during chordate evolution, and that the ancestral cluster contained an "alpha-like," a "beta-like," and a "gamma-like" subunit gene. 3. Our laboratory has identified two additional GABA(A) receptor polypeptides (the beta4 and gamma4 subunits) in a number of vertebrate species; these do not appear to be present in mammals. We discuss here the relationship of the corresponding genes to other GABA(A) receptor genes, and conclude that their products are orthologous to the mammalian theta and epsilon subunits, respectively. 4. The GABA(A) receptor has a number of binding sites for compounds such as BZs, barbiturates, neurosteroids, and certain volatile anaesthetics. However, the only site at which endogenous compounds are thought to be active is the steroid site; this binds steroids such as certain metabolites of progesterone and deoxycorticosterone, which are synthesized in the periphery and CNS. Since the in vivo functional relevance, if any, of binding sites for other classes of compounds (such as the BZs) is unknown, the significance of differences in primary sequence, between different receptor subunits, is uncertain. We suggest that a possibly more important consequence of gene duplication is that it permitted greater flexibility in the level, pattern and regulation of expression of GABA(A) receptor genes.


Abdominal neoplasia (excluding urogenital tract).
Neoplasia of the equine gastrointestinal tract and abdominal organs occurs predominantly in geriatric horses, although lymphoma and hepatocellular carcinoma and a few other neoplasms can be found in young horses. This article discusses diagnostics that can be used in weight-loss situations, suspicious of neoplasia, as well as tumors themselves including clinical signs, diagnostic tools, histopathologic appearance, and management.