Virus infection suppresses Nicotiana benthamiana adaptive phenotypic plasticity.
Competition and parasitism are two important selective forces that shape life-histories, migration rates and population dynamics. Recently, it has been shown in various pathosystems that parasites can modify intraspecific competition, thus generating an indirect cost of parasitism. Here, we investigated if this phenomenon was present in a plant-potyvirus system using two viruses of different virulence (Tobacco etch virus and Turnip mosaic virus). Moreover, we asked if parasitism interacted with the shade avoidance syndrome, the plant-specific phenotypic plasticity in response to intraspecific competition. Our results indicate that the modification of intraspecific competition by parasitism is not present in the Nicotiana benthamiana--potyvirus system and suggests that this phenomenon is not universal but depends on the peculiarities of each pathosystem. However, whereas the healthy N. benthamiana presented a clear shade avoidance syndrome, this phenotypic plasticity totally disappeared when the plants were infected with TEV and TuMV, very likely resulting in a fitness loss and being another form of indirect cost of parasitism. This result suggests that the suppression or the alteration of adaptive phenotypic plasticity might be a component of virulence that is often overlooked.


Subjective memory complaint only relates to verbal episodic memory performance in mild cognitive impairment.
A cognitive concern from the patient, informant, or clinician is required for the diagnosis of mild cognitive impairment (MCI); however, the cognitive and neuroanatomical correlates of complaint are poorly understood. We assessed how self-complaint relates to cognitive and neuroimaging measures in older adults with MCI. MCI participants were drawn from the Alzheimer's Disease Neuroimaging Initiative and dichotomized into two groups based on the presence of self-reported memory complaint (no complaint n = 191, 77 ± 7 years; complaint n = 206, 73 ± 8 years). Cognitive outcomes included episodic memory, executive functioning, information processing speed, and language. Imaging outcomes included regional lobar volumes (frontal, parietal, temporal, cingulate) and specific medial temporal lobe structures (hippocampal volume, entorhinal cortex thickness, parahippocampal gyrus thickness). Linear regressions, adjusting for age, gender, race, education, Mini-Mental State Examination score, mood, and apolipoprotein E4 status, found that cognitive complaint related to immediate (β = -1.07, p < 0.001) and delayed episodic memory performances assessed on a serial list learning task (β = -1.06, p = 0.001) but no other cognitive measures or neuroimaging markers. Self-reported memory concern was unrelated to structural neuroimaging markers of atrophy and measures of information processing speed, executive functioning, or language. In contrast, subjective memory complaint related to objective verbal episodic learning performance. Future research is warranted to better understand the relation between cognitive complaint and surrogate markers of abnormal brain aging, including Alzheimer's disease, across the cognitive aging spectrum.


Manure and tillage use in remediation of eroded land and impacts on soil chemical properties.
Soil loss through wind and water erosion is an ongoing problem in semiarid regions. A thin layer of top soil loss over a hectare of cropland could be corresponding to tons of productive soil loss per hectare. The objectives of this study were to evaluate the influence of beef feedlot manure, tillage and legume grass mixtures on changes in soil quality and nutrient components. The study was initiated in 2006 on an eroded site near Akron, Colorado, on a Norka-Colby very-fine sandy loam (fine-silty, mixed, mesic, Aridic, Argiustolls). Tillage treatments were no-tillage, shallow tillage (sweeps operations with V-blade) and deep tillage (DT; moldboard plow operations). In one set of plots, DT was implemented biannually (DT-2); and in another set the DT was done once at the initiation of the experiment in 2006. Amendments consisted of beef manure and urea (46-0-0), N fertilizer. Both amendments were added at low and high rates. A control treatment, with no fertilizer or manure added, was included with no-tillage and shallow tillage only. Six years of manure addition and tillage significantly altered soil chemical properties compared with fertilizer and grass legume mixtures. Across all the tillage treatments, at the 0-30 cm depth, soil pH from 2006 to 2012, was reduced 1.8 fold with high-manure compared with high-fertilizer treatment. Soil EC, Na, and SAR increased by 2.7 fold while soil P increase by 3.5 fold with high-manure treatment compared with low-manure from 2006 to 2012 across all the tillage treatments at the surface 0-30 cm. Soil organic carbon associated with high-manure was 71% higher than low-manure and 230% higher than high-fertilizer treatments in the 0-60 cm depth. Similar patterns were observed with soil total N. Overall, manure amendments greatly improved the soil nutrient status on this eroded site. However, the legume grass mixtures showed little effect on improving soils chemical properties. The micronutrients supplied by manure improved the soil nutrient status compared with inorganic fertilizer, the grass, and the grass-legume treatments. We concluded that more than six years are needed to measure significant improvements in soil quality from specific treatments, specifically fertilizer, grasses, and grass-legume mixtures in such eroded crop land.


Neurological sequelae of bacterial meningitis.
We reported on occurrence and impact of neurological sequelae after bacterial meningitis. We reviewed occurrence of neurological sequelae in children and adults after pneumococcal and meningococcal meningitis. Most frequently reported sequelae are focal neurological deficits, hearing loss, cognitive impairment and epilepsy. Adults with pneumococcal meningitis have the highest risk of developing focal neurological deficits, which are most commonly caused by cerebral infarction, but can also be due to cerebritis, subdural empyema, cerebral abscess or intracerebral bleeding. Focal deficits may improve during clinical course and even after discharge, but a proportion of patients will have persisting focal neurological deficits that often interfere in patient's daily life. Hearing loss occurs in a high proportion of patients with pneumococcal meningitis and has been associated with co-existing otitis. Children and adults recovering from bacterial meningitis without apparent neurological deficits are at risk for long-term cognitive deficits. Early identification of neurological sequelae is important for children to prevent additional developmental delay, and for adults to achieve successful return in society after the disease. Neurological sequelae occur in a substantial amount of patients following bacterial meningitis. Most frequently reported sequelae are focal neurological deficits, hearing loss, cognitive impairment and epilepsy.


A new percutaneous method for inframammary fold reconstruction in implant-based breast reconstruction: Vertical pendulum suture.
Several operative techniques for inframammary fold (IMF) reconstruction have been described and have resolved the shortcomings of conventional methods. However, there are still difficulties with IMF reconstruction, that is, performance through small mastectomy scars, creation of a smooth IMF curve, transfer of external IMF markings to the interior chest wall, or determining correct IMF without an implant in place. We have used a type of anchor suture with a completely percutaneous approach, the vertical pendulum suture (VP suture), to reconstruct the IMF easily in implant-based breast reconstruction.The VP suture requires a pair of skin incisions a few millimeters in length (incisions A and B). The needle passes through the subcutaneous tissue from incision A, the chest wall, again through the subcutaneous tissue, and exits from incision B. Then, the needle passes through the edge of the dermis from incision B, the superficial layer of the subcutaneous tissue, again through the other edge of the dermis, and exits from incision A. The knot is tied and buried in the subcutaneous tissue. The whole technique can be performed percutaneously without visualizing the inside of the pocket. A retrospective case series study of photographs and chart review was conducted for all cases of unilateral implant-based breast reconstruction performed from December 2016 to December 2017 at Ina Central Hospital, Ina, Japan.Nine consecutive patients underwent unilateral implant-based breast reconstruction. Five patients treated using the VP suture were included in this study. All 5 patients showed good esthetic results over the follow-up period (average, 11 months). Scalloped appearance was observed in all patients, but flattened spontaneously and disappeared within 3 months postoperatively. There were no complications, such as hematoma, infection, skin necrosis, pneumothorax, seroma, scar contracture, or implant injury.The VP suture is completely percutaneous, parallel to the IMF, and is easy to perform at any time during surgery regardless of whether the implant is in place or not. IMF reconstruction is facilitated by freeing the surgeon from the need to visualize the inside of the pocket.


The impact of socioeconomic status on stage at presentation, receipt of diagnostic imaging, receipt of treatment and overall survival in colorectal cancer patients.
Socioeconomic factors influence patterns of care in colorectal cancer. Our study investigates the impact of socioeconomic status (SES) on stage at presentation, receipt of diagnostic imaging, receipt of treatment and overall survival (OS) in a universal healthcare system. The Ontario Cancer Registry (OCR) was accessed to identify a cohort of patients diagnosed with colorectal adenocarcinoma from 2007 to 2016 in Ontario, Canada. SES was measured using median neighborhood income divided into quintiles (Q1-Q5; Q1 = lowest income). Logistic regression analyses were used to evaluate stage, imaging and treatment. Cox proportional hazards models were used to evaluate OS. All endpoints were adjusted for demographics and comorbidities with OS models also adjusting for stage, imaging and treatment. In total, 39 802 colon and 13 164 rectal patients were identified. Lower SES was associated with advanced stage at presentation in both cohorts (Q1 vs Q5: Colon odds ratio [OR] = 1.08, P = .046, rectal OR = 1.25, P < .0001). Lower SES colon patients were less likely to receive adjuvant oxaliplatin (Q1 vs Q5: OR = 0.78, P < .001) and all palliative chemotherapies studied including oxaliplatin (Q1 vs Q5: OR = 0.60, P < 0.0001), irinotecan (Q1 vs Q5: OR = 0.65, P < .0001), bevacizumab (Q1 vs Q5: OR = 0.70, P < .001), cetuximab (Q1 vs Q5: OR = 0.40, P = .0053) and panitumumab (Q1 vs Q5: OR = 0.54, P = .0036). In rectal patients, lower SES was associated with decreased receipt of rectal cancer resection for stages I-III (Q1 vs Q5: OR = 0.78, P < .001), adjuvant oxaliplatin (Q1 vs Q5: OR = 0.72, P = .0020) and palliative chemotherapies including oxaliplatin (Q1 vs Q5: OR = 0.59, P < .001), irinotecan (Q1 vs Q5: OR = 0.53, P < .001) and bevacizumab (Q1 vs Q5: OR = 0.71, P = .046). All survival models identified poorer OS for lower SES patients (total colorectal; Q1 vs Q5: Hazard ratio [HR] = 1.25, P < .0001). These findings suggest disparities persist even within universal healthcare.


Mechanisms of Kale (Brassica oleracea var. acephala) Tolerance to Individual and Combined Stresses of Drought and Elevated Temperature.
Rising temperatures and pronounced drought are significantly affecting biodiversity worldwide and reducing yields and quality of Brassica crops. To elucidate the mechanisms of tolerance, 33 kale accessions (B. oleracea var. acephala) were evaluated for individual (osmotic and elevated temperature stress) and combined stress (osmotic + temperature). Using root growth, biomass and proline content as reliable markers, accessions were evaluated for stress responses. Four representatives were selected for further investigation (photosynthetic performance, biochemical markers, sugar content, specialized metabolites, transcription level of transcription factors NAC, HSF, DREB and expression of heat shock proteins HSP70 and HSP90): very sensitive (392), moderately sensitive (395), tolerant (404) and most tolerant (411). Accessions more tolerant to stress conditions were characterized by higher basal content of proline, total sugars, glucosinolates and higher transcription of NAC and DREB. Under all stress conditions, 392 was characterized by a significant decrease in biomass, root growth, photosynthesis performance, fructan content, especially under osmotic and combined stress, a significant increase in HSF transcription and HSP accumulation under temperature stress and a significant decrease in NAC transcription under all stresses. The most tolerant accession under all applied stresses, 411 showed the least changes in all analyzed parameters compared with the other accessions.


Systemic anticancer therapy in gynecological cancer patients with renal dysfunction.
Chronic kidney disease is a common occurrence in patients with gynecological cancer. Systemic anticancer treatment in such patients is a challenge for clinicians because of altered drug pharmacokinetics. For those drugs that are excreted mainly by the kidneys, decreased renal function may lead to increased systemic exposure and increased toxicity. Dose adjustment based on pharmacokinetic changes is required in this situation to avoid life-threatening toxicity. In this review, we summarize the nephrotoxicity and pharmacokinetic data of agents commonly used in systemic anticancer treatment of gynecological cancers and dose adjustment guidelines in the presence of impaired renal function. We review 17 medications that need dose adjustment (cisplatin, carboplatin, doxorubicin, epirubicin, cyclophosphamide, ifosfamide, topotecan, irinotecan, etoposide, capecitabine, bleomycin, methotrexate, actinomycin D, granulocyte-macrophage colony-stimulating factor, metoclopramide, cimetidine, and diphenhydramine) as well as 27 drugs that do not (paclitaxel, docetaxel, pegylated liposomal doxorubicin, gemcitabine, oxaliplatin, fluorouracil, vincristine, letrozole, anastrozole, tamoxifen, leuprorelin, megestrol, gefitinib, erlotinib, trastuzumab, leucovorin, granulocyte colony-stimulating factor, erythropoietin, ondansetron, granisetron, palonosetron, tropisetron, dolasetron, aprepitant, dexamethasone, lorazepam, and diazepam). We also review the formulae commonly used to estimate creatinine clearance, including Cockcroft-Gault, Chatelut, Jelliffe, Wright, and the Modification of Diet in Renal Disease study formulae.


The relationship among area, elevation, and regional species richness in neotropical birds.
The elevational gradient of species richness is often claimed to mirror the latitudinal gradient and has traditionally been explained by assuming a decrease in productivity with elevation and more recently by Rapoport's rule. The influence of area on the pattern has rarely been considered. Analyses of all South American tropical land birds (more than one-fourth of the extant bird species on Earth) are used to examine four species richness/elevation models: null model, Rapoport's rule, and monotonic or hump-shaped productivity/species richness relationships. To quantify the area effect, species-area curves were created for seven elevational zones. Not accounting for area, species richness declined monotonically with elevation, but area accounted for 67%-91% of the variation in species richness per zone. When area was factored out, a hump-shaped pattern emerged, with more species in the 500-1,000-m (P<.005) and 1,000-1,500-m zones (P<.10) than in the 0-500-m zone. Rapoport's rule and the monotonic productivity/species richness relationship were thus not supported. Instead, elevational turnover rates and numbers of shared species between zones suggested that the hump-shaped pattern reflects geometric constraints (as predicted by the null model) imposed by the narrow span of the gradient, and it is suggested that midelevational zones may represent sink habitats.


Impact of cultivar, harvesting time, and seasonal variation on the content of biophenols in olive mill waste.
Olive mill waste (OMW) contains substantial amounts of valuable antioxidant biophenols that can be recovered for possible applications in food, pharmaceutical, and cosmetic industries. However, the impact of cultivar, harvesting time, and seasonal variation on the phenolic composition of OMW has not yet been assessed. Total phenols, antioxidant activity, and phenol profiles of OMW extracts from five different Australian-grown cultivars (Barnea, Correggiola, Manzanillo, Mission, and Paragon) were studied at four different harvesting times in the 2004 season. The impact of seasonal variation was assessed by comparing total phenol content, antioxidant activity, and phenol profile of two cultivars (Correggiola and Mission) harvested in the 2004 and 2005 seasons. The phenol content and antioxidant activity at different harvesting times were mainly a function of the olive cultivar. Harvesting time had a quantitative effect rather than a qualitative effect on the phenol profile. Intercultivar and harvesting time variation accounted for a 2-5-fold change in the total phenol and antioxidant capacity, while levels of individual biophenols experienced up to 50-fold change. The phenol content and antioxidant capacity of OMW significantly changed between seasons with different variation patterns for different cultivars.


Squamosal Suture Synostosis: Incidence, Associations, and Implications for Treatment.
Squamosal suture craniosynostosis is thought to be a relatively rare entity. In the authors' experience, it is underreported in imaging examinations and the existing literature. The authors sought to determine the incidence of squamosal synostosis, whether it is increasing in frequency, and its relationship with synostosis of the major calvarial sutures.Patients undergoing computed tomography imaging for suspected craniosynostosis over a 15-year period were reviewed by a plastic surgeon and pediatric neuroradiologist. Patients with synostosis of the squamosal sutures were identified and involvement of additional sutures, gender, and the presence of a known syndromic diagnosis were recorded. Patients greater than 4 years of age or those with prior craniofacial surgery were excluded.One hundred twenty-five patients met inclusion criteria, 26 of whom had squamosal suture synostosis (26/125, 20.8%). Squamosal synostosis was found in isolation in 3 patients (3/26, 11.5%), with 1 additional major suture in 10 patients (10/26, 38.5%), and ≥2 major sutures in 13 patients (13/26, 50%). Squamosal synostosis was more common in patients with a syndromic diagnosis (11/26 syndromic, 15/99 nonsyndromic, P < 0.001). Eleven of 26 patients with squamosal synostosis were identified in the radiology report (42.3%).Craniosynostosis of the squamosal suture is much more common than previously reported and can contribute to abnormal head shape in isolation, or in combination with major sutures. Squamosal suture synostosis is underdiagnosed clinically and radiologically, although insufficient evidence exists to determine if its true incidence is increasing.


Low mitochondrial glycerol phosphate dehydrogenase and pyruvate carboxylase in pancreatic islets of Zucker diabetic fatty rats.
The enzyme activities of mitochondrial glycerol phosphate dehydrogenase (mGPD) (EC 188.8.131.52) and pyruvate carboxylase (PC) (EC 22.214.171.124) have been reported to be low in the pancreatic islet of several rodent models of NIDDM. The present study was undertaken to discern whether mGPD is abnormal in the Zucker diabetic fatty (ZDF) rat (ZDF/Gmi-fa/fa), an animal model of NIDDM in which insulin secretion is unable to counteract the insulin resistance associated with the obesity that characterizes this model. Experiments were performed in prediabetic 6-week-old ZDF rats in comparison with 12-week-old overtly hyperglycemic animals and, as controls, Zucker lean (ZL) rats (ZDF/Gmi-+/fa or -+/+) and Wistar rats (+/+) of the same ages. The enzyme activity of mGPD was 32 and 18% of normal in islets of 6- and 12-week-old ZDF rats, respectively (P < 0.001 by analysis of variance). The activity of PC, which like mGPD is relatively abundant in the pancreatic islet, was 17 and 10% of normal in the islets of 6- and 12-week-old ZDF rats, respectively (P < 0.001). The activity of mGPD was normal in islets from ZL rats. However, PC activity was slightly lower in islets of 6- (51% of normal, P = 0.007) and 12-week-old (67% of normal, P = 0.01) ZL rats. The amounts of mGPD protein, as judged from Western analysis, and of PC protein, as judged from probing transblots with streptavidin that binds to biotin-containing enzymes, roughly correlated with the enzyme activities. This indicates that the decreased enzyme activities are caused by the decreased net synthesis of these enzymes rather than by the decreased activity of a normal amount of enzyme. The enzyme activity of succinate dehydrogenase, a control for mGPD, was normal in the ZL and ZDF rats. An incidental finding of the current study was the discovery of beta-methylcrotonyl-CoA carboxylase and propionyl-CoA carboxylase in the islet. Levels of these enzymes were also normal. Although reductions in mGPD and PC may contribute to the abnormal insulin secretion present in overt diabetes, they are modest compared with the severe reductions seen in inherited inborn errors of metabolism. Because of this and because more than a single enzyme is affected and the enzymes in the islet are diminished in more than one rodent model of NIDDM, these reductions are unlikely to represent the primary genetic defect in the ZDF rat. Since ZDF rats are euglycemic at 6 weeks of age and ZL animals are euglycemic throughout life and since these animals demonstrate low enzyme activities, this evidence suggests that it is not hyperglycemia but rather some other component of the diabetic syndrome that is responsible for the reductions in these enzymes.


Thermodynamic equilibrium dose-response models for MERS-CoV infection reveal a potential protective role of human lung mucus but not for SARS-CoV-2.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Middle East respiratory syndrome coronavirus (MERS-CoV) infect the human respiratory tract. A prototype thermodynamic equilibrium model is presented here for the probability of the virions getting through the mucus barrier and infecting epithelial cells based on the binding affinity (Kmucin) of the virions to mucin molecules in the mucus and parameters for binding and infection of the epithelial cell. Both MERS-CoV and SARS-CoV-2 bind strongly to their cellular receptors, DDP4 and ACE2, respectively, and infect very efficiently both bronchus and lung ex vivo cell cultures which are not protected by a mucus barrier. According to the model, mucin binding could reduce the infectivity for MERS-CoV compared to SARS-CoV-2 by at least 100-fold depending on the magnitude of Kmucin. Specifically Kmucin values up to 106 M-1 have little protective effect and thus the mucus barrier would not remove SARS-CoV-2 which does not bind to sialic acids (SA) and hence would have a very low Kmucin. Depending on the viability of individual virions, the ID50 for SARS-CoV-2 is estimated to be ~500 virions (viral RNA genomic copies) representing 1 to 2 pfu. In contrast MERS-CoV binds both SA and human mucin and a Kmucin of 5 × 109 M-1 as reported for lectins would mop up 99.83% of the virus according to the model with the ID50 for MERS-CoV estimated to be ~295,000 virions (viral RNA genomic copies) representing 819 pfu. This could in part explain why MERS-CoV is poorly transmitted from human to human compared to SARS-CoV-2. Some coronaviruses use an esterase to escape the mucin, although MERS-CoV does not. Instead, it is shown here that "clustering" of virions into single aerosol particles as recently reported for rotavirus in extracellular vesicles could provide a co-operative mechanism whereby MERS-CoV could theoretically overcome the mucin barrier locally and a small proportion of 10 μm diameter aerosol particles could contain ~70 virions based on reported maximum levels in saliva. Although recent evidence suggests SARS-CoV-2 initiates infection in the nasal epithelium, the thermodynamic equilibrium models presented here could complement published approaches for modelling the physical entry of pathogens to the lung based on the fate and transport of the pathogen particles (as for anthrax spores) to develop a dose-response model for aerosol exposure to respiratory viruses. This would enable the infectivity through aerosols to be defined based on molecular parameters as well as physical parameters. The role of the spike proteins of MERS-CoV and SARS-CoV-2 binding to SA and heparan sulphate, respectively, may be to aid non-specific attachment to the host cell. It is proposed that a high Kmucin is the cost for subsequent binding of MERS-CoV to SAs on the cell surface to partially overcome the unfavourable entropy of immobilisation as the virus adopts the correct orientation for spike protein interactions with its protein cellular receptor DPP4.


Vitamin D insufficiency and frailty syndrome in older adults living in a Northern Taiwan community.
This study explored the association between vitamin D insufficiency and frailty syndrome defined by the Fried Frailty Index (FFI) and the Edmonton Frail Scale (EFS) in a northern Taiwan community. Data of 215 subjects participating in an integrated interventional trial involving community-dwelling older adults with a high frailty risk were analyzed. Subjects were first screened by telephone interview and then evaluated at a local hospital with questionnaires, physical performance tests, and serum 25(OH)D measurements. Of the 215 participants, 31% had 25(OH)D insufficiency (< 20 ng/ml). Frail subjects based on the FFI were older, had lower Mini-Mental Status Exam (MMSE) scores, Barthel Index (BI) scores, and 25(OH)D levels. Using the EFS, frailer cases were more likely to be female, have less education, higher comorbid conditions, lower MMSE scores, lower Barthel Index scores, and lower 25(OH)D levels. The associations between insufficient 25(OH)D status and both frailty scales were significant. After adjustment of variables, the odds ratio of 25(OH)D insufficiency was 10.74 (95% CI 2.60-44.31) for frail versus robust individuals. The prevalence of vitamin D insufficiency was high in this population. There was a strong association between vitamin D insufficiency and the FFI. Vitamin D measurements and supplements are suggested for high-risk older people.


Has the sensitivity of soybean cultivars to ozone pollution increased with time? An analysis of published dose-response data.
The rising trend in concentrations of ground-level ozone (O3 ) - a common air pollutant and phytotoxin - currently being experienced in some world regions represents a threat to agricultural yield. Soybean (Glycine max (L.) Merr.) is an O3 -sensitive crop species and is experiencing increasing global demand as a dietary protein source and constituent of livestock feed. In this study, we collate O3 exposure-yield data for 49 soybean cultivars, from 28 experimental studies published between 1982 and 2014, to produce an updated dose-response function for soybean. Different cultivars were seen to vary considerably in their sensitivity to O3 , with estimated yield loss due to O3 ranging from 13.3% for the least sensitive cultivar to 37.9% for the most sensitive, at a 7-h mean O3 concentration (M7) of 55 ppb - a level frequently observed in regions of the USA, India and China in recent years. The year of cultivar release, country of data collection and type of O3 exposure used were all important explanatory variables in a multivariate regression model describing soybean yield response to O3 . The data show that the O3 sensitivity of soybean cultivars increased by an average of 32.5% between 1960 and 2000, suggesting that selective breeding strategies targeting high yield and high stomatal conductance may have inadvertently selected for greater O3 sensitivity over time. Higher sensitivity was observed in data from India and China compared to the USA, although it is difficult to determine whether this effect is the result of differential cultivar physiology, or related to local environmental factors such as co-occurring pollutants. Gaining further understanding of the underlying mechanisms that govern the sensitivity of soybean cultivars to O3 will be important in shaping future strategies for breeding O3 -tolerant cultivars.


An Aberrant Abductor Digiti Minimi Muscle Crossing Guyon's Canal.
Anomalous hypothenar muscles in the wrist are relatively common with 47% prevalence, and their possible consequences associated with Guyon's canal are well known. The accessory of the abductor digiti minimi muscle (ADM) is known to be one of the causes of ulnar tunnel syndrome or ulnar artery thrombosis. A unique ADM was found in the volar wrist region of an 87-year-old male cadaver passing through Guyon's canal.


[Dissectors and clamps for pediatric cardiovascular surgery].
The new multi-purpose instruments for cardiovascular surgery in infants and newborns are designed. As compared to their analogues they have smaller mass and dimensions, they are atraumatic and more convenient which makes it possible to use them widely in children's cardiovascular surgery.


Disposition kinetics and bioavailability of piperacillin and cephapirin in mares.
The pharmacokinetics of piperacillin (430 mg/kg.b.wt.) and cephapirin (20 mg/kg.b.wt.) were investigated following a single intravenous and intramuscular injection in normal mares. The serum concentration-time curve following a single intravenous injection of both antibiotics obeyed a two-compartment open model. After intravenous dose, piperacillin and cephapirin were transferred from central to peripheral compartment (k12) with values 0.46 and 0.52 h-1, while their passages from peripheral to central compartment (k21) were equal to 0.56 and 0.49 h-1, respectively. The elimination half-lives [t0.5(beta)] following intravenous injection were 6.94 and 3.82 h for piperacillin and cephapirin, respectively. Piperacillin and cephapirin were cleared after intravenous injection by all clearance processes in the body (CItot.) at rates of 5.52 and 0.67 ml/min., respectively. The absorption half-lives [t0.5(ab)] of piperacillin and cephapirin following a single intramuscular injection were 0.46 and 0.88 h., respectively. The calculated maximum [Cmax.] and minimum [Cmin.] serum concentrations to establish a proper multiple dosage regimen were 52.94, 4.50 micromilligrams (for piperacillin) and 10.18, 2.20 micromilligrams (for cephapirin), respectively. The mean systemic bioavailabilities of piperacillin and cephapirin following a single intramuscular injection were 85.47% and 67.89%, respectively. The in-vitro protein binding percent was 19.23% for piperacillin and 52.62% for cephapirin.


[Total diverticulosis of the large intestine, complicated by ischemic colitis with development of multiple inflammatory polyps].
One observation of total colon diverticulosis in a male of 62 is described. Clinical signs (abdominal pains, blood in faeces, vomiting) persisted for 7 years and was aggravated by ileus. Instrumental examination revealed multiple colon diverticula, stenosing villous tumour of sigmoid colon. Besides pseudodiverticula, chronic colitis with multiple inflammatory polyps stenosing the lumen of the sigmoid colon and simulating a villous tumour was found. The conclusion is made of the ischemic nature of the colitis complicating the course of diverticulosis.


Solid-state nitrogen-15 nuclear magnetic resonance analysis of biologically reduced 2,4,6-trinitrotoluene in a soil slurry remediation.
Soil contaminated with 2,4,6-trinitrotoluene (TNT) and spiked with [14C]- and [15N3]-TNT was subjected to an anaerobic-aerobic soil slurry treatment and subsequently analyzed by radiocounting and solid-state 15N nuclear magnetic resonance (NMR) spectroscopy. This treatment led to a complete disappearance of extractable radioactivity originating from TNT and almost all of the radioactivity was recovered in the insoluble soil fraction. As revealed by solid-state 15N NMR, a major fraction of partially reduced metabolites of TNT was immobilized into the soil during the early stage of the anaerobic treatment, although some of the compounds (i.e., aminodinitrotoluenes and azoxy compounds) were extractable by methanol. Considerable 15N intensity was assigned to condensation products of TNT metabolites. A smaller signal indicated the formation of azoxy N. This signal and the signal for nitro groups were not observed at the end of the anaerobic phase, revealing further reduction and/or transformation of their corresponding compounds. An increase of the relative proportion of the condensation products occurred with increasing anaerobic incubation. Aerobic incubation resulted in a further decrease of aromatic amines, presumably due to oxidative transformations or their involvement in further condensation reactions. The results of the study demonstrate that the anaerobic-aerobic soil slurry treatment represents an efficient strategy for immobilizing reduced TNT in soils.


Reduced apoptosis and increased deletion mutations at Aprt locus in vivo in mice exposed to repeated ionizing radiation.
Exposure to ionizing radiation (IR) is a risk factor for carcinogenesis because it is a mutagen. However, a single 4-Gy whole body X-ray exposure only induced a modest increase of mutations at the Aprt reporter gene locus in mouse T cells. Intriguingly, when the same dose of IR was given in a fractionated protocol (1 Gy x 4 at weekly intervals), there was a strong induction of Aprt mutations in T cells. Many of these were mutations that arose via interstitial deletions inclusive of Aprt or by intragenic deletions. We hypothesized that the weekly fractionated X-ray exposures select for somatic cells with reduced p53 expression and/or reduced apoptosis, which, in turn, may have facilitated the accumulation of interstitial deletions, as in p53-deficient mice. We indeed found that splenocytes of mice with three previous exposures (1 Gy x 4 in total) were more resistant to X-ray-induced apoptosis than those of mice exposed to X-rays for the first time (1 Gy total). Thus, repeated X-ray radiation selects for reduced apoptosis in vivo. However, this reduced apoptosis is p53-independent, because p53 induction and the up-regulation of genes downstream of p53, such as Bax and p21, were similar between the 1-Gy and 1 Gy x 4 groups. Reduced apoptosis probably allows the generation of more mutations, particularly deletion mutations. Because both reduced apoptosis and increased somatic mutation are risk factors for carcinogenesis, they may contribute to the paradigm in which different radiation exposure schemes are varied in their efficiency in inducing lymphomagenesis.


Ethos of independence across regions in the United States: the production-adoption model of cultural change.
Contemporary U.S. culture has a highly individualistic ethos. Nevertheless, exactly how this ethos was historically fostered remains unanalyzed. A new model of dynamic cultural change maintains that sparsely populated, novel environments that impose major threats to survival, such as the Western frontier in the United States during the 18th and 19th centuries, breed strong values of independence, which in turn guide the production of new practices that encourage self-promotion and focused, competitive work. Faced with few significant threats to survival, residents in traditional areas are likely to seek social prestige by adopting existing practices of other, higher status groups. Because of both the massive economic success of the frontier and the official endorsement of the frontier by the federal government, eastern residents of the United States in the 18th and 19th centuries may have actively adopted the frontier practices of independence, thus incorporating the frontier ethos of independence to form the contemporary U.S. national culture. Available evidence is reviewed, and implications for further research on cultural change are suggested.


Effect of "no added salt diet" on blood pressure control and 24 hour urinary sodium excretion in mild to moderate hypertension.
The incidence of Hypertension as a major cardiovascular threat is increasing. The best known diet for hypertensives is 'no added salt diet'. In this study we evaluated the effect of 'no added salt diet' on a hypertensive population with high dietary sodium intake by measuring 24 hour urinary sodium excretion. In this single center randomized study 80 patients (60 cases and 20 controls) not on any drug therapy for hypertension with mild to moderate hypertension were enrolled. 24 hour holter monitoring of BP and 24 hour urinary sodium excretion were measured before and after 6 weeks of 'no added salt diet'. There was no statistically significant difference between age, weight, sex, Hyperlipidemia, family history of hypertension, mean systolic and diastolic BP during the day and at night and mean urinary sodium excretion in 24 hour urine of case and control groups. Seventy eight percent of all patients had moderate to high salt intake. After 6 week of 'no added salt diet' systolic and diastolic BP significantly decreased during the day (mean decrease: 12.1/6.8 mmhg) and at night (mean decrease: 11.1/5.9 mmhg) which is statistically significant in comparison to control group (P 0.001 and 0.01). Urinary sodium excretion of 24 hour urine decreased by 37.1 meq/d +/- 39,67 mg/dl in case group which is statistically significant in comparison to control group (p: 0.001). Only 36% of the patients, after no added salt diet, reached the pretreatment goal of 24 hour urinary sodium excretion of below 100 meq/dl (P:0.001). Despite modest effect on dietary sodium restriction, no added salt diet significantly decreased systolic and diastolic BP and so it should be advised to every hypertensive patient. Clinicaltrial.govnumber NCT00491881.


Is the Carli index flawed?: assessing the case for the new retail price index RPIJ.
The paper discusses the recent decision of the UK's Office for National Statistics to replace the controversial Carli index with the Jevons index in a new version of the retail price index-RPIJ. In doing so we make three contributions to the way that price indices should be selected for measures of consumer price inflation when quantity information is not available (i.e. at the 'elementary' level). Firstly, we introduce a new price bouncing test under the test approach for choosing index numbers. Secondly, we provide empirical evidence on the performance of the Carli and Jevons indices in different contexts under the statistical approach. Thirdly, applying something analogous to the principle of insufficient reason, we argue contrary to received wisdom in the literature, that the economic approach can be used to choose indices at the elementary level, and moreover that it favours the use of the Jevons index. Overall, we conclude that there is a case against the Carli index and that the Jevons index is to be preferred.


Rotary ATPases: models, machine elements and technical specifications.
Rotary ATPases are molecular rotary motors involved in biological energy conversion. They either synthesize or hydrolyze the universal biological energy carrier adenosine triphosphate. Recent work has elucidated the general architecture and subunit compositions of all three sub-types of rotary ATPases. Composite models of the intact F-, V- and A-type ATPases have been constructed by fitting high-resolution X-ray structures of individual subunits or sub-complexes into low-resolution electron densities of the intact enzymes derived from electron cryo-microscopy. Electron cryo-tomography has provided new insights into the supra-molecular arrangement of eukaryotic ATP synthases within mitochondria and mass-spectrometry has started to identify specifically bound lipids presumed to be essential for function. Taken together these molecular snapshots show that nano-scale rotary engines have much in common with basic design principles of man made machines from the function of individual "machine elements" to the requirement of the right "fuel" and "oil" for different types of motors.


Poliovirus Vaccination Induces a Humoral Immune Response That Cross Reacts With SARS-CoV-2.
Background: Millions have been exposed to SARS-CoV-2, but the severity of resultant infections has varied among adults and children, with adults presenting more serious symptomatic cases. Children may possess an immunity that adults lack, possibly from childhood vaccinations. This retrospective study suggests immunization against the poliovirus may provide an immunity to SARS-CoV-2. Methods: Publicly available data were analyzed for possible correlations between national median ages and epidemiological outbreak patterns across 100 countries. Sera from 204 adults and children, who were immunized with the poliovirus vaccine, were analyzed using an enzyme-linked immunosorbent assay. The effects of polio-immune serum on SARS-CoV-2-induced cytopathology in cell culture were then evaluated. Results: Analyses of median population age demonstrated a positive correlation between median age and SARS-CoV-2 prevalence and death rates. Countries with effective poliovirus immunization protocols and younger populations have fewer and less pathogenic cases of COVID-19. Antibodies to poliovirus and SARS-CoV-2 were found in pediatric sera and in sera from adults recently immunized with polio. Sera from polio-immunized individuals inhibited SARS-CoV-2 infection of Vero cell cultures. These results suggest the anti-D3-pol-antibody, induced by poliovirus vaccination, may provide a similar degree of protection from SARS-CoV-2 to adults as to children. Conclusions: Poliovirus vaccination induces an adaptive humoral immune response. Antibodies created by poliovirus vaccination bind the RNA-dependent RNA polymerase (RdRp) protein of both poliovirus and SARS-CoV-2, thereby preventing SARS-CoV-2 infection. These findings suggest proteins other than "spike" proteins may be suitable targets for immunity and vaccine development.


5-Azacytidine/5-Azacitidine.
The hypomethylating agent 5-Azacytidine epigenetically modulates various genes, including tumor suppressor genes. For many years, the "new agent", which was first discovered in the 1960s, remained fairly unobtrusive in the rank of salvage treatment options for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). When the significance of epigenetics in tumorigenesis became clear, 5-Azacytidine attracted new attention. Finally, it was the first drug approved for the treatment of all categories of MDS, and its survival benefit over best conventional care was confirmed. Today, in many clinical situations, when aggressive therapies including allogeneic hematopoietic cell transplantation are not an option, 5-Azacytidine is the first treatment of choice. Preliminary data on combinations of the hypomethylating agent with other new drugs are promising, and innovative strategies involving immune modulation and regenerative tissue repair hold a broad potential for future developments.


Müllerian inhibiting substance/anti-Müllerian hormone: A novel treatment for gynecologic tumors.
Müllerian inhibiting substance (MIS), also called anti-Müllerian hormone (AMH), is a member of the transforming growth factor-β super-family of growth and differentiation response modifiers. It is produced in immature Sertoli cells in male embryos and binds to MIS/AMH receptors in primordial Müllerian ducts to cause regression of female reproductive structures that are the precursors to the fallopian tubes, the surface epithelium of the ovaries, the uterus, the cervix, and the upper third of the vagina. Because most gynecologic tumors originate from Müllerian duct-derived tissues, and since MIS/AMH causes regression of the Müllerian duct in male embryos, it is expected to inhibit the growth of gynecologic tumors. Purified recombinant human MIS/AMH causes growth inhibition of epithelial ovarian cancer cells and cell lines in vitro and in vitro via MIS receptor-mediated mechanism. Furthermore, several lines of evidence suggest that MIS/AMH inhibits proliferation in tissues and cell lines of other MIS/AMH receptor-expressing gynecologic tumors such as cervical, endometrial, breast, and in endometriosis as well. These findings indicate that bioactive MIS/AMH recombinant protein should be tested in patients against tumors expressing the MIS/AMH receptor complex, perhaps beginning with ovarian cancer because it has the worst prognosis. The molecular tools to identify MIS/AMH receptor expressing ovarian and other cancers are in place, thus, it is possible to select patients for treatment. An MIS/AMH ELISA exists to follow administered doses of MIS/AMH, as well. Clinical trials await the production of sufficient supplies of qualified recombinant human MIS/AMH for this purpose.


Purification and characterization of the serum amyloid A3 enhancer factor.
Serum amyloid A (SAA) is a major acute-phase protein synthesized and secreted mainly by the liver. In response to acute inflammation, its expression may be induced up to 1000-fold, primarily as a result of a 200-fold increase in the rate of SAA gene transcription. We showed previously that cytokine-induced transcription of the SAA3 gene promoter requires a transcriptional enhancer that contains three functional elements: two CCAAT/enhancer-binding protein (C/EBP)-binding sites and a third site that interacts with a constitutively expressed transcription factor, SAA3 enhancer factor (SEF). Each of these binding sites as well as cooperation among their binding factors is necessary for maximum transcription activation by inflammatory cytokines. Deletion or site-specific mutations in the SEF-binding site drastically reduced SAA3 promoter activity, strongly suggesting that SEF is important in SAA3 promoter function. To further elucidate its role in the regulation of the SAA3 gene, we purified SEF from HeLa nuclear extracts to near homogeneity by using conventional liquid chromatography and DNA affinity chromatography. Ultraviolet cross-linking and Southwestern experiments indicated that SEF consisted of a single polypeptide with an apparent molecular mass of 65 kDa. Protein sequencing and antibody supershift experiments identified SEF as transcription factor LBP-1c/CP2/LSF. Cotransfection of SEF expression vector with SAA3-luciferase reporter resulted in approximately a 5-fold increase in luciferase activity. Interestingly, interleukin-1 treatment of SEF-transfected cells caused dramatic synergistic activation (31-fold) of the SAA3 promoter. In addition to its role in regulating SAA3 gene expression, we provide evidence that SEF could also bind in a sequence-specific manner to the promoters of the alpha(2)-macroglobulin and Aalpha-fibrinogen genes and to an intronic enhancer of the human Wilm's tumor 1 gene, suggesting a functional role in the regulation of these genes.


[Human erythrocyte protein kinases (author's transl)].
Cyclic AMP dependent and independent protein kinase activities are present in membrane as well as cytosol of human erythrocyte. Red cell membrane contains at least: 1) a cAMP dependent histone kinase type I using ATP as phosphoryl donor; 2) a cAMP independent casein kinase using ATP or GTP as phosphoryl donor; this kinase probably phosphorylates erythrocyte spectrin. In lysate of human red cell there are two or three cAMP dependent protein kinase type I and II and one cAMP independent casein kinase. Characteristics of these protein kinase activities are reviewed. Membrane substrates are numbered taking into account that the activity assays are often of dubious value. Several phosphorylation abnormalities previously reported in hematologic and non-hematologic disorders are still uncertain and at present time not any red cell protein kinase deficiency has been demonstrated.


A comparison of the consensus and clinical definitions of pancreatitis with a proposal to redefine post-endoscopic retrograde cholangiopancreatography pancreatitis.
We evaluated the correlation between the consensus and clinical definitions of pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP), with the objective of updating and revising the definition of post-ERCP pancreatitis (PEP). Three hundred patients were subjected to serial serum amylase & lipase levels testing and abdominal computed tomography scan for abdominal pain after ERCP. Main outcome measures included the correlation between consensus and clinical definitions. Using consensus criteria, 25 patients had acute pancreatitis (11 of mild and 14 of moderate severity). Forty-three patients had acute pancreatitis using the clinical definitions (18 of mild and 25 of moderate severity). At 4 hours, serum hyperamylasemia of under 1.5-fold and at 12 hours a serum hyperamylasemia of under 2-fold had a negative predictive value of 0.94 for development of PEP. Serum hyperamylasemia following ERCP had a poor positive predictive value for PEP. Clinical and consensus definitions are poorly correlated; use of the latter leads to significant underrecognition of PEP. The adoption of clinical definition results in uniformity of diagnosis of pancreatitis for clinical care and research. Serum amylase levels at 4 and 12 hours after ERCP have a high negative predictive value for PEP.


Increased envelope spike density and stability are not required for the neutralization resistance of primary human immunodeficiency viruses.
Previous observations that the gp120 envelope glycoprotein contents of some primary, clade B human immunodeficiency virus type 1 (HIV-1) isolates were higher than those of laboratory-passaged HIV-1 isolates suggested the hypothesis that increased envelope glycoprotein spike density or stability contributes to the relative neutralization resistance of the primary viruses. To test this, the structural, replicative, and neutralization properties of a panel of recombinant viruses with HIV-1 envelope glycoproteins from divergent clades were examined in an env complementation assay. In this system, although the spike density and stability of envelope glycoproteins from primary HIV-1 isolates were not greater than those from a laboratory-adapted isolate, relative resistance to neutralizing antibodies and soluble CD4 was observed for the viruses with primary envelope glycoproteins. Thus, neither high envelope glycoprotein spike density nor stability is necessary for the relative neutralization resistance of primary HIV-1 viruses.


The Role of Psychiatry in Treating Burnout Among Nurses During the Covid-19 Pandemic.
The prevalence of burnout among US registered nurses ranges from 35 to 45%. In one study, nurses had twice the rate of depression compared with other health care professionals. Owing to the Covid-19 pandemic, burnout is a major threat to the stability of the workforce on the front lines. Consultation-liaison (C/L) psychiatry can provide assistance through liaison meetings, stress management programs, and curbside consults to help reduce the risk of burnout. Narrative medicine programs, mindfulness-based stress reduction, and meditation apps are additional means to alleviate stress. Given the current challenges facing C/L psychiatry and the mental health field in general, there is an urgent need to overcome stigma and financial barriers to make treatment readily accessible.


Distribution and responsiveness of rat anti-Müllerian hormone during ovarian development and VCD-induced ovotoxicity.
Anti-Müllerian hormone (AMH) is produced by granulosa cells in primary to small antral follicles of the adult ovary and helps maintain primordial follicles in a dormant state. The industrial chemical, 4-vinylcyclohexene diepoxide (VCD) causes specific ovotoxicity in primordial and small primary follicles of mice and rats. Previous studies suggest that this ovotoxicity involves acceleration of primordial to primary follicle recruitment via interactions with the Kit/Kit ligand signaling pathway. Because of its accepted role in inhibiting primordial follicle recruitment, the present study was designed to investigate a possible interaction between AMH and VCD-induced ovotoxicity. Protein distribution of AMH was compared in neonatal and adult F344 rat ovaries. AMH protein was visualized by immunofluorescence microscopy in large primary and secondary follicles of the adult ovary, but in small primary follicles in neonatal rat ovaries. In cultured postnatal day (PND) 4 F344 rat ovaries, VCD exposure (30 μM, 2-8 days) decreased (P<0.05) AMH mRNA (d4-8) and protein (d6-8). Recombinant AMH (100-400 mg/ml) in PND4 ovaries cultured 8 days±VCD (30 μM) caused an increase (P<0.05) in primordial, and a decrease (P<0.05) in small primary follicles, supporting that AMH retarded primordial follicle recruitment. However, no concentration of AMH had an effect on VCD-induced ovotoxicity. Whereas, VCD caused a reduction in expression of AMH (d4-d8), it followed previously reported initial disruptions in Kit signaling induced by VCD (d2). Thus, collectively, these results do not support a mechanism whereby VCD causes ovotoxicity via generalized activation of primordial follicle recruitment, but instead provide further support for the specificity of other intracellular mechanisms involved in VCD-induced ovotoxicity.


Don't Get Wound Up: Revised Fluoroquinolone Breakpoints for Enterobacteriaceae and Pseudomonas aeruginosa.
Fluoroquinolones remain some of the more commonly prescribed antimicrobial agents in the United States, despite the wide array of reported side effects that are associated with their use. In 2019, the Clinical and Laboratory Standards Institute revised the fluoroquinolone antimicrobial susceptibility testing breakpoints for both Enterobacteriaceae and Pseudomonas aeruginosa This breakpoint revision was deemed necessary on the basis of pharmacokinetic and pharmacodynamic analyses suggesting that the previous breakpoints were too high, in addition to the inability of the previous breakpoints to detect low-level resistance to this antibiotic class. In this minireview, we review the published data in support of this revision, as well as the potential challenges that these breakpoint revisions are likely to pose for clinical laboratories.


Cognitive processes and attitudes in bipolar disorder: a study into personality, dysfunctional attitudes and attention bias in patients with bipolar disorder and their relatives.
Research in cognitive processes and attitudes in bipolar disorder is scarce and has provided mixed findings, possibly due to differences in current mood state. It is unclear whether alterations in cognitive processes and attitudes are only related to the depressive mood states of bipolar patients or also represent a vulnerability marker for the development of future (depressive) episodes. This was investigated in the current study. Both implicit (attentional bias for emotional words) and explicit (dysfunctional attitudes and personality characteristics) measures of cognitive processes and attitudes were assessed in 77 bipolar patients with varying levels of depressive symptoms (depressed=17, euthymic n=60), their healthy first-degree relatives (n=39) and a healthy control group (n=61). Analyses of variance were used to investigate differences between groups. Mildly depressed patients with bipolar disorder demonstrated an attentional bias away from positive emotional words and showed increased dysfunctional attitudes and higher levels of neuroticism. Euthymic patients were largely comparable to healthy controls and only differed from controls in higher levels of neuroticism. Relatives were similar to controls on all measures, although they significantly differed from bipolar patients in displaying less neuroticism and more extraversion. No firm conclusions regarding causality can be drawn from the associations that were found between cognitive processes and attitudes and the evolution of mood symptoms in bipolar disorder. Alterations in cognitive processes and attitudes in bipolar patients appear to be mostly related to the expression of mood symptomatology rather than to the vulnerability for bipolar disorder.


Expanded RED products and loci containing CAG/CTG repeats on chromosome 17 (ERDA1) and chromosome 18 (CTG18.1) in trans-generational pairs with bipolar affective disorder.
The purpose of the present study was to further test if expanded CAG repeats detected by the repeat expansion detection (RED) method in bipolar affective disorder (BPAD) are correlated with ERDA1 (17q21.3) and/or CTG18.1 (18q21.1) loci expansions, and changes of phenotype severity in successive generations (anticipation). The sample was designed to analyze ERDA1 and CTG18.1 expansions in trans-generational pairs of affected individuals (parent-offspring pairs: G1 and G2). Clinical and genetic information was available on 95 two-generations pairs. We found in our sample no one patient carrying an expanded allele at the CTG18.1 locus. This observation is true for all individuals in G1 and G2. Using the conditional logistic regression, no statistical difference was observed between the two generations for ERDA1 alleles (chi(2) = 0.2, P = 0.65). These data do not support the correlation between expanded RED products (RED fragments >120) and expanded alleles at ERDA1 in trans-generational pairs with BPAD. We were not able to detect any correlation for CTG18.1. Earlier age at onset in offspring generation was also not associated with expanded RED products explained by expanded ERDA1 alleles.


Pregnancy in women with epilepsy : preliminary results of Kerala registry of epilepsy and pregnancy.
Eighty-five women with epilepsy were followed up for reproductive functions under the registry of epilepsy and pregnancy. 32 of them had completed the pregnancy. Their mean age was 26 years and mean seizure frequency was 0.7 during current pregnancy. Nineteen of them (59.4%) had generalized epilepsy. Nine of them were not on any anti epileptic drugs (AED), 23 women were on various AEDs, 19 being on monotherapy. Only 40% of the women were taking folic acid during pregnancy. Pregnancy ended as spontaneous abortion in one patient. Nearly one third required cesarean section. Majority (87.5%) had term babies. Three (10.7%) babies had birth asphyxia. Six babies (21.4%) had low birth weight. Congenital malformations were detected in four cases (12.5%). Malformations included neural tube defects, talipes equinovarus and other minor anomalies. These babies were exposed to sodium valproate, carbamazepine or phenobarbitone. The risk of malformation was significantly greater (p<0.05) when the mother had generalized epilepsy. The odds ratio for risk of malformation was much higher with sodium valproate (6) than that with carbamazepine (1.2) or phenobarbitone (0.8). Majority of women with epilepsy had safe pregnancy and childbirth without any aggravation of epilepsy.


Dehydroalanine analog of glutathione: an electrophilic busulfan metabolite that binds to human glutathione S-transferase A1-1.
Elimination of hydrogen sulfide from glutathione (GSH) converts a well known cellular nucleophile to an electrophilic species, gamma-glutamyldehydroalanylglycine (EdAG). We have found that a sulfonium metabolite formed from GSH and busulfan undergoes a facile beta-elimination reaction to give EdAG, which is an alpha,beta-unsaturated dehydroalanyl analog of GSH. EdAG was identified as a metabolite of busulfan in a human liver cytosol fraction. EdAG condenses with GSH in a Michael addition reaction to produce a lanthionine thioether [(2-amino-5-[[3-[2-[[4-amino-5-hydroxy-5-oxopentanoyl]amino]-3-(carboxymethylamino)-3-oxopropyl]sulfanyl-1-(carboxymethylamino)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid); GSG], which is a nonreducible analog of glutathione disulfide. EdAG was less cytotoxic than busulfan to C6 rat glioma cells. GSH and EdAG were equally effective in displacing a glutathione S-transferase (GST) isozyme (human GSTA1-1) from a GSH-agarose column. The finding of an electrophilic metabolite of GSH suggests that alteration of cellular GSH concentrations, irreversible nonreducible glutathionylation of proteins, and interference with GST function may contribute to the toxicity of busulfan.


Highly Sensitive Ultraviolet and Visible Wavelength Sensor Composed of Two Identical Perovskite Nanofilm Photodetectors.
This work reports the design of a wavelength sensor composed of two identical perovskite (FA0.85 Cs0.15 PbI3 ) photodetectors (PDs) that are capable of discriminating incident wavelength in a quantitative way. Due to strong wavelength-dependent absorption coefficient, the penetration depth of the photons in the FA0.85 Cs0.15 PbI3 nanofilms increases with the increasing wavelength, leading to a gradual decrease of photo-generated current for PD1, but an increase of photocurrent in PD2, according to the theoretical simulation of Technology Computer Aided Design. This special evolution of photo-generated current as a function of wavelength facilitates the quantitative determination of the wavelength since the current ratio of both PDs monotonously decreases with the increase of wavelength from 265 to 810 nm. The average absolute error and the average relative error are estimated to be 7.6 nm and 1.68%, respectively, which are much better than other semiconductors materials-based wavelength sensors previously reported. It is believed that the present perovskite film-based wavelength sensor will have potential application in the future color/spectrum optoelectronic devices.


Investigating the red shift between in vitro and in vivo urocanic acid photoisomerization action spectra.
Trans-urocanic acid (UCA) is found in the upper layer of the skin and UV irradiation induces its photoisomerization to cis-UCA. Cis-UCA mimics some of the immunosuppressive properties of UV exposure. The wavelength dependence for in vitro photoisomerization of trans-UCA (15 microM) over the spectral range 250 nm-340 nm (10 nm intervals) was determined. The action spectrum revealed that maximal cis-UCA production occurred at 280 nm, which is red-shifted by 10-12 nm from its absorption peak at 268 nm and differs markedly from the reported action spectra for cis-UCA production in mouse skin in vivo, which peaks at 300-310 nm. The reasons for the red shift between the in vitro and in vivo action spectra are not clear. There is limited evidence suggesting that the UV absorption maximum of trans-UCA red shifts from 268 nm in vitro to 310 nm on interaction with stratum corneum proteins in vivo. This phenomenon was investigated by applying trans-UCA (2.5 mg/cm2) in an oil emulsion to isolated human stratum corneum. After incubation at 37 degrees C for 1 h, the absorption spectra of stratum corneum with UCA and with oil only were compared using a Xe arc source and a spectroradiometer. A moderate red shift in trans-UCA absorption from approximately 268 nm to 280 nm was observed. In summary, we suggest that the 10-12 nm red shift between the UCA absorption spectrum peak and the action spectrum peak in vitro may be accounted for by the wavelength dependence of quantum yields reported over the 254-313 nm range. The red shift between the in vitro and in vivo photoisomerization action spectra may result from the 10 to 12 nm red shift in the absorption of UCA in association with stratum corneum proteins, combined with increasing quantum yields over the 254-313 nm range.


Functionalized graphene oxide as a vehicle for targeted drug delivery and bioimaging applications.
Graphene oxide (GO) has attracted tremendous attention as a most promising nanomaterial among the carbon family since it emerged as a polynomial functional tool with rational applications in diverse fields such as biomedical engineering, electrocatalysis, biosensing, energy conversion, and storage devices. Despite having certain limitations due to its irreversible aggregation performance owing largely to the strong van der Waals interactions, efforts have been made to smartly engineer its surface chemistry for realistic multimodal applications. The use of such GO-based engineered devices has increased rapidly in the last few years, principally due to its excellent properties, such as huge surface area, honeycomb-like structure allowing vacant interstitial space to accommodate compounds, sp2 hybridized carbon, improved biocompatibility and cell surface penetration due to electronic interactions. Amongst multifaceted GO dynamics, in this review, attempts are made to discuss the advanced applications of GO or graphene-based materials (GBNs) in the biomedical field involving drug or therapeutic gene delivery, dual drug or drug-gene combination targeting, special delivery of drug cocktails to the brain, stimuli-responsive release of molecular payloads, and Janus-structured smart applications for polar-nonpolar combination drug loading followed by targeting together with smart bioimaging approaches. In addition, the advantages of duel-drug delivery systems are discussed in detail. We also discuss various electronic mechanisms, and detailed surface engineering to meet microcosmic criteria for its utilization, various novel implementations of engineered GO as mentioned above, together with discussions of its inevitable toxicity or disadvantages. We hope that the target audience, belonging to biomedical engineering, pharmaceutical or material science fields, may acquire relevant information from this review which may help them design future studies in this field.


Secreted Frizzled-related protein 3 (sFRP3)-mediated suppression of interleukin-6 receptor release by A disintegrin and metalloprotease 17 (ADAM17) is abrogated in the osteoarthritis-associated rare double variant of sFRP3.
To avoid malformation and disease, tissue development and homoeostasis are co-ordinated precisely in time and space. Secreted Frizzled-related protein 3 (sFRP3), encoded by the Frizzled-related protein gene (FRZB), acts as an antagonist of Wnt signalling in bone development by delaying the maturation of proliferative chondrocytes into hypertrophic chondrocytes. A disintegrin and metalloprotease 17 (ADAM17) is a transmembrane protease that is essential for developmental processes and promotes cartilage maturation into bone. sFRP3 is chondroprotective and is expressed in chondrocytes of healthy articular cartilage. Upon damage to cartilage, sFRP3 is down-regulated. Rare variants of sFRP3 are associated with osteoarthritis. The present study demonstrates a novel function of sFRP3 in suppression of the enzymatic activity of ADAM17 which results in the inhibition of ADAM17-meditated interleukin-6 receptor (IL-6R) shedding. By contrast, the rare double variant of sFRP3 failed to suppress ADAM17. The shed soluble IL-6R (sIL-6R) is linked to inflammation, cartilage degeneration and osteolysis. Accordingly, enhanced activity of ADAM17 in cartilage, caused by the expression of the rare double sFRP3 variant, provides an explanation for the genetic effect of sFRP3 variants in joint disease. The finding that sFRP3 interacts with the ADAM17 substrate IL-6R also suggests a new regulatory mechanism by which the substrate is protected against shedding.


Potential Points of Intervention to Minimize the Impact of Parents' Adverse Childhood Experiences on Child Mental Health.
Children of parents who experienced adverse childhood experiences (ACEs) are at elevated risk for mental health (MH) issues. The goal of this study was to explore the relationships between parent ACEs and child MH and to identify potential mediators and points of psychosocial intervention. Participants were 1307 children aged 5 to 9 years from diverse backgrounds and their primary caregivers. Using cross-sectional questionnaire data, we used structural equation modeling to examine the research questions. Parent ACEs were directly related to child MH issues (β = 0.189, p < 0.001). This relationship was fully mediated by parent MH (β = 0.374, p < 0.001; β = 0.246, p < 0.001) and positive parenting behaviors (β = -0.237, p < 0.001; β = -0.556, p < 0.001). High parent ACEs were negatively associated with parent MH (β = 0.374, p < 0.001), which was then negatively associated with parenting behaviors (β = -0.500, p < 0.001), which was then negatively associated with child MH (β = -0.600, p < 0.001). Parent MH maintained a significant, though attenuated, direct relationship with child MH (β = 0.102, p < 0.05). Parents with high ACEs but who have good mental health and positive parenting behaviors demonstrated no impact of their ACEs on their children's mental health. Providing MH care to parents and parenting programs may be strategies for improving children's MH. Parenting behavior assessment is recommended for clinicians when pediatric patients present with MH concerns.


Resistance to foliage feeding aphid in wheat.
Experimental trials were conducted at Integrated Pest Management Programme, National Agriculture Research Centre Islamabad, to evaluate the resistance of host plants (cereals) against Rhopalosiphum padi (L.). For evaluation of susceptibility, twenty varieties/-advanced lines of National Uniform Wheat Yield Trails (NUWYT) Normal (N) of year 2004-2005 were used. In seedling bulk tests varieties/advanced lines were grouped into three categories resistant, moderately resistant and susceptible. Data from seedling bulk tests showed that DN-47 and PR 87 lines of wheat were resistant to aphid as compared to the other varieties/-advanced lines. In antixenosis tests varieties/-advanced lines were grouped into three categories, least preferred, moderately preferred, highly preferred. Lines V-01180, DN-47 and PR-84 were least preferred, sixteen varieties/-advanced lines were moderately preferred and only one variety V-9021 was found to be highly preferred.


Analysis of somatostatin receptors and somatostatin promoter methylation in human gastric cancer.
Somatostatin (SST) is a gut peptide that is able to inhibit the growth of tumor cells in gastric cancer and other types of cancer. The present study investigated the mRNA and protein levels of SST and SST receptors (SSTRs) in human gastric cancer, and detected the DNA methylation of the SST promoter. The protein levels of SST were detected using a radioimmunoassay in 102 human gastric tissue specimens (51 pairs of samples from 51 gastric cancer patients, each pair of samples included a cancer tissue and a normal tissue sample). SST and SSTR mRNA expression was assessed by reverse transcription-PCR (RT-PCR), while SST promoter methylation was examined using quantitative methylation-specific PCR (qMSP) in 51 pairs of tissues. The association between SST protein and RNA levels and SST methylation and gastric cancer were also analyzed. The protein levels of SST were decreased in the gastric cancer group compared with those of the normal group (5.091±0.994 vs. 7.399±0.956 pg/mg; P<0.01). The RT-PCR analysis indicated that the mRNA levels of SST (0.218±0.183 vs. 0.456±0.331; P<0.001) and SSTRs in the gastric cancer group were lower compared with those of the normal gastric tissue group. The methylation proportion of SST was 45.1% (23/51) in the carcinoma group and 3.9% (2/51) in the normal group. In conclusion, SST promoter methylation is a common event in human gastric cancer and is connected with a decrease in SST protein and RNA levels and associated with gastric carcinogens.


Appraisal of foliar spray of iron and salicylic acid under artificial magnetism on morpho-physiological attributes of pea (Pisum sativum L.) plants.
The appraisal of foliar treatment of iron (Fe) and salicylic acid (SA) on plant under artificial magnetism is very crucial in understanding its impact on growth and development of plants. The present study was designed to document the potential role of Fe and SA on pea (Pisum sativum L.) Matore variety exposed to different magnetism treatments (geomagnetism and artificial magnetism). Thus a pot experiment was conducted using Completely Randomized Design under factorial with three replicates. Various artificial magnetic treatment were applied in pots prior to sowing. Further, 15 days germinated pea seedlings were foliarly supplemented with 250 ppm Fe and 250μM SA, moreover after 20 days of foliar fertilization plants were harvested to analyze and record various morpho-physiological attributes. Data elucidate significant variations in pea plants among different treatments. Artificial magnetism treatments in combination with foliar application of Fe and SA significantly improved various growth attributes (root and shoot length, fresh and dry weights of root and shoot, leaf area), photosynthetic pigments (Chl a, b and carotenoids) and the contents of soluble sugars. However, oxidative stress (H2O2 and MDA) enhanced under different magnetism treatment but foliar application of Fe and SA hampered the production of reactive oxygen species thereby limiting the concentration of H2O2 and MDA in plant tissues. Furthermore the accumulation of nutrients (iron, potassium and nitrate) profoundly increased under artificial magnetism treatment specifically under Fe and SA foliar treatment excluding nitrate where Fe foliar treatment tend to limit nitrate in plant. Consequently, the present research interestingly highlights progressive role of Fe and SA foliar treatment on pea plants under artificial magnetism. Thus, foliar supplementation may be suggested for better growth and development of plants combined with magnetic treatments.


Temporal phase unwrapping: application to surface profiling of discontinuous objects.
The recently proposed technique of temporal phase unwrapping has been used to analyze the phase maps from a projected-fringe phase-shifting surface profilometer. A sequence of maps is acquired while the fringe pitch is changed; the phase at each pixel is then unwrapped over time independently of the other pixels in the image to provide an absolute measure of surface height. The main advantage is that objects containing height discontinuities are profiled as easily as smooth ones. This contrasts with the conventional spatial phase-unwrapping approach for which the phase jump across a height discontinuity is indeterminate to an integral multiple of 2pi. The error in height is shown to decrease inversely with the number of phase maps used.


Hyperactive MEK1 Signaling in Cortical GABAergic Neurons Promotes Embryonic Parvalbumin Neuron Loss and Defects in Behavioral Inhibition.
Many developmental syndromes have been linked to genetic mutations that cause abnormal ERK/MAPK activity; however, the neuropathological effects of hyperactive signaling are not fully understood. Here, we examined whether hyperactivation of MEK1 modifies the development of GABAergic cortical interneurons (CINs), a heterogeneous population of inhibitory neurons necessary for cortical function. We show that GABAergic-neuron specific MEK1 hyperactivation in vivo leads to increased cleaved caspase-3 labeling in a subpopulation of immature neurons in the embryonic subpallial mantle zone. Adult mutants displayed a significant loss of parvalbumin (PV), but not somatostatin, expressing CINs and a reduction in perisomatic inhibitory synapses on excitatory neurons. Surviving mutant PV-CINs maintained a typical fast-spiking phenotype but showed signs of decreased intrinsic excitability that coincided with an increased risk of seizure-like phenotypes. In contrast to other mouse models of PV-CIN loss, we discovered a robust increase in the accumulation of perineuronal nets, an extracellular structure thought to restrict plasticity. Indeed, we found that mutants exhibited a significant impairment in the acquisition of behavioral response inhibition capacity. Overall, our data suggest PV-CIN development is particularly sensitive to hyperactive MEK1 signaling, which may underlie certain neurological deficits frequently observed in ERK/MAPK-linked syndromes.


Assessment of perinatal hepatitis B and rubella prevention in New Hampshire delivery hospitals.
To evaluate current performance on recommended perinatal hepatitis B and rubella prevention practices in New Hampshire. Data were extracted from 2021 paired mother-infant records for the year 2000 birth cohort in New Hampshire's 25 delivery hospitals. Assessment was done on the following: prenatal screening for hepatitis B and rubella, administration of the hepatitis B vaccine birth dose to all infants, administration of hepatitis B immune globulin to infants who were born to hepatitis B surface antigen-positive mothers, rubella immunity, and administration of in-hospital postpartum rubella vaccine to rubella nonimmune women. Prenatal screening rates for hepatitis B (98.8%) and rubella (99.4%) were high. Hepatitis B vaccine birth dose was administered to 76.2% of all infants. All infants who were born to hepatitis B surface antigen-positive mothers also received hepatitis B immune globulin. Multivariate logistic regression showed that the month of delivery and infant birth weight were independent predictors of hepatitis B vaccination. The proportion of infants who were vaccinated in January and February 2000 (48.5% and 67.5%, respectively) was less than any other months, whereas the proportion who were vaccinated in December 2000 (88.2%) was the highest. Women who were born between 1971 and 1975 had the highest rate of rubella nonimmunity (9.5%). In-hospital postpartum rubella vaccine administration was documented for 75.6% of nonimmune women. This study documents good compliance in New Hampshire's birthing hospitals with national guidelines for perinatal hepatitis B and rubella prevention and highlights potential areas for improvement.


Morphological and Molecular Characterization of Exophiala polymorpha sp. nov. Isolated from Sporotrichoid Lymphocutaneous Lesions in a Patient with Myasthenia Gravis.
Exophiala species are capable of causing cutaneous and subcutaneous infections in immunocompromised patients. An Exophiala isolate was cultured from a biopsy specimen of a lesion on the forearm of a patient with myasthenia gravis. The patient also had lesions on the palm and distal aspects of the hand, which were successfully treated with a long-term course of itraconazole. A detailed morphological and molecular characterization of the isolate was undertaken. Phylogenetic analysis of the internal transcribed spacer region and portions of the β-tubulin and translation elongation factor 1-alpha genes indicated that the isolate was a novel species closely related to but genetically distinct from species within the Exophiala spinifera clade; the name Exophiala polymorpha sp. nov. is proposed. Morphologically, E. polymorpha most closely resembles E. xenobiotica but it differs in possessing phialides bearing prominent, wide collarettes, and it does not produce chlamydospores.


Specific cyclooxygenase-2 inhibitors: what have we learned since they came into widespread clinical use?
Specific inhibitors of cyclooxygenase-2 were introduced into widespread clinical use in 1999. Since that time, celecoxib and rofecoxib have become two of the most commonly prescribed medications in the United States. Clinical trials using these medications for arthritis and pain have uniformly demonstrated efficacy superior to that of placebo and similar to that of nonsteroidal anti-inflammatory drugs. However, controversy surrounding the proper place of cyclooxygenase-2 inhibitors in the hierarchy of treatment for arthritis continues, based primarily on their higher cost compared with that of acetaminophen and nonsteroidal anti-inflammatory drugs. A decreased risk of gastrointestinal toxicity remains the primary justification for using the more expensive cyclooxygenase-2 inhibitors in preference to nonsteroidal anti-inflammatory drugs. The renal and cardiovascular effects of rofecoxib and celecoxib have been investigated in relation to nonsteroidal anti-inflammatory drugs and to one another. The data with respect to alteration in renal function, lower extremity edema, and hypertension indicates that cyclooxygenase-2 inhibitors affect the kidney in a manner similar to that of nonsteroidal anti-inflammatory drugs. The data comparing the cyclooxygenase-2 inhibitors is difficult to interpret because it is not clear that comparable doses have been used in clinical trials. The potential thrombogenic risk of cyclooxygenase-2 inhibitors remains controversial, and conflicting data exist. It remains important to increase our understanding of the place of these agents in clinical practice from the perspective of efficacy, toxicity, and cost.


Vascular permeability and the optic disc. Changes after bilateral common carotid ligation in the rat.
The permeability of retinal blood vessels to intravenously injected horseradish peroxidase was examined two to seven days after bilateral common carotid ligation in rats. Light and electron microscopy revealed leakage from the blood vessels of the optic disc. This leakage appeared to result from vesicular transport across the endothelium; the interendothelial tight junctions we examined remained intact and there was no evidence of endothelial cell death. The intraretinal blood vessels and the retinal pigment epithelium retained their normal impermeability to horseradish peroxidase. Cellular edema was present at the optic disc, manifested as swollen axons. Glial cells remained normal in appearance and the extracellular space was not enlarged. These observations clarify those previously derived from funduscopy and fluorescein angiography, which revealed disc edema and hyperfluorescence.


The present status of highly selective vagotomy.
Peptic ulcer has been the subject of extensive investigation in the search for a curative operation free of complications. Highly selective vagotomy is an elegant physiological approach to the problem, and has excited widespread interest. The reported results in uncomplicated duodenal ulcer disease indicate an almost nil mortality, a very low incidence of recurrent ulceration, a marked reduction in basal and stimulated acid secretion, and little or no interference with gastric emptying, hormone metabolism, or pancreatic and biliary function. The good clinical results at one year appear to be maintained at five years. Its use in the management of gastric ulceration and the complications of peptic ulcer disease also appears promising.


Differential requirements for the Ets transcription factor Elf-1 in the development of NKT cells and NK cells.
E26 Transformation specific (Ets) family transcription factors control the expression of a large number of genes regulating hematopoietic cell development and function. Two such transcription factors, Ets-1 and myeloid Elf-1-like factor (MEF), have been shown to play critical roles in both natural killer (NK)- and NKT-cell development, but not in the development of conventional T cells. In this study, we address the role of E74-like factor 1 (Elf-1), another Ets family transcription factor that is closely related to MEF but divergent from Ets-1, in NK- and NKT-cell development using Elf-1-deficient (Elf-1(-/-)) mice. Whereas the proportion of NK cells in Elf-1(-/-) mice was normal, the proportion of NKT cells was significantly reduced in the thymus and periphery of Elf-1(-/-) mice compared with wild-type (WT) mice. Although Ets-1-deficient mice lack NKT cells altogether, Elf-1(-/-) mice exhibited only a partial block in NKT-cell development caused by a cell-intrinsic defect in the selection, survival, and maturation of NKT cells. In addition, residual NKT cells found in Elf-1(-/-) mice produced less cytokine upon antigen stimulation compared with WT NKT cells. Our data demonstrate that Elf-1 plays an important and nonredundant role in the development and function of NKT cells, but is not involved in NK-cell development.


Neighborhood socioeconomic deprivation and minority composition are associated with better potential spatial access to the ground-truthed food environment in a large rural area.
Little is known about spatial inequalities and potential access to the food environment in rural areas. In this study, we assessed the food environment in a 6-county rural region of Texas (11,567 km2) through ground-truthed methods that included direct observation and on-site Global Positioning System technology to examine the relationship between neighborhood inequalities (e.g., socioeconomic deprivation and minority composition) and network distance from all 101 rural neighborhoods to the nearest food store (FS). Neighborhood deprivation was determined from socioeconomic characteristics using 2000 census block group (CBG) data. Network distances were calculated from the population-weighted center of each CBG to the nearest supermarket, grocery, convenience, and discount store. Multiple regression models examined associations among deprivation, minority composition, population density, and network distance to the nearest FS. The median distance to the nearest supermarket was 14.9 km one way (range 0.12 to 54.0 km). The distance decreased with increasing deprivation, minority composition, and population density. The worst deprived neighborhoods with the greatest minority composition had better potential spatial access to the nearest FS. For >20% of all rural residents, their neighborhoods were at least 17.7 km from the nearest supermarket or full-line grocery or 7.6 km from the nearest convenience store. This makes food shopping a challenge, especially in rural areas that lack public transportation and where many have no vehicular access. Knowledge of potential access to the food environment is essential for combining environmental approaches and health interventions so that families, especially those in rural areas, can make healthier food choices.


Resilin and chitinous cuticle form a composite structure for energy storage in jumping by froghopper insects.
Many insects jump by storing and releasing energy in elastic structures within their bodies. This allows them to release large amounts of energy in a very short time to jump at very high speeds. The fastest of the insect jumpers, the froghopper, uses a catapult-like elastic mechanism to achieve their jumping prowess in which energy, generated by the slow contraction of muscles, is released suddenly to power rapid and synchronous movements of the hind legs. How is this energy stored? The hind coxae of the froghopper are linked to the hinges of the ipsilateral hind wings by pleural arches, complex bow-shaped internal skeletal structures. They are built of chitinous cuticle and the rubber-like protein, resilin, which fluoresces bright blue when illuminated with ultra-violet light. The ventral and posterior end of this fluorescent region forms the thoracic part of the pivot with a hind coxa. No other structures in the thorax or hind legs show this blue fluorescence and it is not found in larvae which do not jump. Stimulating one trochanteral depressor muscle in a pattern that simulates its normal action, results in a distortion and forward movement of the posterior part of a pleural arch by 40 microm, but in natural jumping, the movement is at least 100 microm. Calculations showed that the resilin itself could only store 1% to 2% of the energy required for jumping. The stiffer cuticular parts of the pleural arches could, however, easily meet all the energy storage needs. The composite structure therefore, combines the stiffness of the chitinous cuticle with the elasticity of resilin. Muscle contractions bend the chitinous cuticle with little deformation and therefore, store the energy needed for jumping, while the resilin rapidly returns its stored energy and thus restores the body to its original shape after a jump and allows repeated jumping.


Characterization of the promoter region of the c-yes proto-oncogene: the importance of the GC boxes on its promoter activity.
In this study we cloned the 5' flanking sequence of the human c-yes gene and identified its promoter region. A 0.53 kilobase pair (kbp) fragment containing the 5' terminus of the c-yes gene showed strong promoter activity when placed upstream of the bacterial chloramphenicol acetyltransferase (CAT) gene and transfected into monkey CV-1 cells. By nuclease S1 mapping multiple transcriptional start sites were detected within the promoter region. Nucleotide sequence analysis revealed that the c-yes promoter region had high G + C contents (64%) and contained six GC box-like sequences (one at the 5' distal region and five in a cluster at the 5' proximal region), but not a TATA box. These features of the c-yes promoter region are similar to those of other protooncogenes, ras-family genes and c-raf-1, and some house-keeping genes. Deletion analysis suggested that the most downstream 0.21 kbp region is primarily important for the promoter activity. This 0.21 kbp region contains one major and another minor transcriptional start site. Five GC box-like sequences were located within this region, and four of them were shown to bind with purified Sp1 transcription factor. Furthermore, using the base-substituted mutants of the Sp1-binding sites, each GC box in the cluster (GC1 to GC4) was shown to affect the c-yes gene expression.


Structural features of envelope proteins on hepatitis C virus-like particles as determined by anti-envelope monoclonal antibodies and CD81 binding.
The envelope glycoprotein E2 of hepatitis C virus (HCV) is a major component of the viral envelope. Knowledge of its topologic features and antigenic determinants in virions is crucial in understanding the viral binding sites to cellular receptor(s) and the induction of neutralizing antibodies. The lack of a robust cell culture system for virus propagation has hampered the characterization of E2 presented on the virion. Here we report the structural features of hepatitis C virus-like particles (HCV-LPs) of the 1a and 1b genotypes as determined by various mouse and human monoclonal anti-envelope antibodies. Our results show that the E2 protein of HCV-LPs reacts with human monoclonal antibodies recognizing conformational determinants. Monoclonal antibodies (mAbs) specific for the hypervariable region 1 (HVR-1) sequence reacted strongly with HCV-LPs, suggesting that the HVR-1 is exposed on the viral surface. Several mAbs recognized both HCV-LPs with equally high affinity, indicating that the corresponding epitopes [amino acids (aa) 192-217 of E1 and aa 412-423, aa 522-531, and aa 640-653 of E2] are conserved in both genotypes and exposed on the surface of the HCV-LP. The E2 and E1/E2 dimers of 1a bound strongly to the recombinant large extracellular loop (LEL) of CD81 (CD81-LEL) of human and African green monkey, while the HCV-LP of 1a bound weakly to human CD81-LEL. E1/E2 dimers and the HCV-LPs of 1b did not bind CD81-LEL, consistent with the notion that CD81 recognition by E2 is strain-specific and does not correlate with permissiveness of infection. A model of the topology and exposed antigenic determinants of the envelope proteins of HCV is proposed.


Attenuation and preserved immunogenic potential of Yersinia pseudotuberculosis mutant strains evidenced in oral pig model.
Experimental oral infection of pigs with a parental Yersinia pseudotuberculosis strain pIB102, serotype O:3 and two mutant isogenic strains - pIB155,DeltayopK and pIB44,DeltaypkA has been carried out. Clinical findings, microbiological and immunological parameters were examined in dynamics from day 7 to day 60 post-infection (p.i.). All types of infections ran asymptomatically, without hyperthermia, loss of appetite, etc. Experiments on the blood parameters demonstrated a transient leucocytosis with lymphocytosis and monocytosis better expressed after yopK infection. Even though pig is usually known as a reservoir of yersiniae, bacterial colonization was found in mesenterial lymph nodes and tonsils on day 7, respectively 14 p.i. with parental strain, and only in tonsils on day 14 p.i. with both mutant strains. The augmented sensitivity of mutants to the bactericidal effect of leukocytes and blood sera is the characteristic feature of attenuation in their pathogenicity, compared to the parental strain. Comparative in vitro experiments on the immune response and immunostimulating capacity of Y. pseudotuberculosis mutant strains verify their preserved immunogenic potential, predominantly in case of yopK. Hyperplasia and strong activation of the lymph tissue of Peyer's patches, mesenterial lymph nodes, tonsils and spleen of pigs challenged with both mutant strains were proved as immunomorphological rearrangements. The results obtained give the reason to claim that the genetically constructed yopK null mutant strain is significantly attenuated but is still immunogenic and has the potential for a live vaccine carrier strain.


Nutritional idiosyncrasies of the golden hamster (Mesocricetus auratus).
The golden hamster has a compartmentalized stomach consisting of a forestomach and a glandular stomach. The forestomach is lined with keratinized epithelium and contains an active microbiol population capable of significant cellulolytic activity. This organ is not essential for life and is the first entrance point for swallowed feed. The hamster, while having a protein requirement like that of the rat, utilizes protein much differently. It ranks soybean meal above a fish protein concentrate and does not utilize added crystalline essential amino acids as such. Acceptance of the hamster as a nutritional surrogate of the rat seems unwarranted.


[Clinical trial of the month. The STENO-2 study: a plea for global and intensive management of the type 2 diabetic patient].
Cardiovascular morbidity is a major burden in patients with type 2 diabetes. The Steno-2 Study compared the effect of a targeted, intensified, multifactorial intervention (n = 80) with that of a conventional treatment (n = 80) on modifiable risk factors for cardiovascular disease in patients with type 2 diabetes and microalbuminuria. After a mean follow-up of 7.8 years, the risk of cardiovascular events was reduced by 53% in the intensive group, and the risk of microvascular events (nephropathy, retinopathy, autonomic neuropathy) by 58-63%. Thus, a target-driven, long-term, intensified intervention aimed at multiple risk factors should be recommended in patients with type 2 diabetes and microalbuminuria.


Hospital-acquired intestinal toxemia botulism in a newly diagnosed adult colon cancer patient.
This manuscript reports a case of intestinal toxemia botulism in an adult with recently diagnosed metastatic colon cancer in whom botulism symptoms began 23 days after hospital admission. Representing the rarest form of botulism presentation in clinical practice, this infectious disease may have developed due to a cluster of predisposing factors that favored Clostridium botulinum colonization and the endogenous production of neurotoxins, among which are previous use of broad-spectrum antibiotics and colon changes related to the development of the neoplasia. This case highlights the importance of considering intestinal toxemia botulism in the differential diagnosis of a patient presenting with symmetrical descending flaccid paralysis, since immediate treatment with botulinum antitoxin may improve clinical outcomes.


Synthesis and biological evaluation of novel pentacyclic triterpene derivatives as potential PPARγ agonists.
Synthesis and biological evaluation of a novel series of substituted pentacyclic triterpene derivatives as potential PPARγ agoinsts and glycogen phosphorylase inhibitors have been described. Compounds 11 and 17 showed potent PPARγ agonistic activity and activated the transcription activity of PPARγ in a dose-dependent manner. On the other hand, eleven compounds exhibited moderate inhibitory activity against rabbit muscle glycogen phosphorylase a (RMGPa), and triterpene 10 was the best one. Structure-activity relationship (SAR) is also discussed.


Paraspinal synovial sarcoma as an unusual postradiation complication in pediatric abdominal neuroblastoma.
The development of a soft-tissue sarcoma is an infrequent but well-known long-term complication of radiotherapy. Malignant fibrous histiocytomas, extraskeletal osteosarcomas, fibrosarcomas, malignant peripheral nerve sheath tumors, and angiosarcomas are most frequently encountered. Radiation-associated synovial sarcomas are uncommon and exceedingly rare in pediatric patients. We report an unusual case of paraspinal synovial sarcoma presenting in an adolescent female 13 years after radiation therapy for her neuroblastoma.


KSR-1 binds to G-protein betagamma subunits and inhibits beta gamma-induced mitogen-activated protein kinase activation.
The protein kinase KSR-1 is a recently identified participant in the Ras signaling pathway. The subcellular localization of KSR-1 is variable. In serum-deprived cultured cells, KSR-1 is primarily found in the cytoplasm; in serum-stimulated cells, a significant portion of KSR-1 is found at the plasma membrane. To identify the mechanism that mediates KSR-1 translocation, we performed a yeast two-hybrid screen. Three clones that interacted with KSR-1 were found to encode the full-length gamma10 subunit of heterotrimeric G-proteins. KSR-1 also interacted with gamma2 and gamma3 in a two-hybrid assay. Deletion analysis demonstrated that the isolated CA3 domain of KSR-1, which contains a cysteine-rich zinc finger-like domain, interacted with gamma subunits. Coimmunoprecipitation experiments demonstrated that KSR-1 bound to beta1 gamma3 subunits when all three were transfected into cultured cells. Lysophosphatidic acid treatment of cells induced KSR-1 translocation to the plasma membrane from the cytoplasm that was blocked by administration of pertussis toxin but not by dominant-negative Ras. Finally, transfection of wild-type KSR-1 inhibited beta1 gamma3-induced mitogen-activated protein kinase activation in cultured cells. These results demonstrate that KSR-1 translocation to the plasma membrane is mediated, at least in part, by an interaction with beta gamma and that this interaction may modulate mitogen-activated protein kinase signaling.