Isolation of a superfamily of candidate disease-resistance genes in soybean based on a conserved nucleotide-binding site.
The tobacco N and Arabidopsis RPS2 genes, among several recently cloned disease-resistance genes, share highly conserved structure, a nucleotide-binding site (NBS). Using degenerate oligonucleotide primers for the NBS region of N and RPS2, we have amplified and cloned the NBS sequences from soybean. Each of these PCR-derived NBS clones detected low-or moderate-copy soybean DNA sequences and belongs to 1 of 11 different classes. Sequence analysis showed that all PCR clones encode three motifs (P-loop, kinase-2, and kinase-3a) of NBS nearly identical to those in N and RPS2. The intervening region between P-loop and kinase-3a of the 11 classes has high (26% average) amino acid sequence similarity to the N gene although not as high (19% average) to RPS2. These 11 classes represent a superfamily of NBS-containing soybean genes that are homologous to N and RPS2. Each class or subfamily was assessed for its positional association with known soybean disease-resistance genes through near-isogenic line assays, followed by linkage analysis in F2 populations using restriction fragment length polymorphisms. Five of the 11 subfamilies have thus far been mapped to the vicinity of known soybean genes for resistance to potyviruses (Rsv1 and Rpv), Phytophthora root rot (Rps1, Rps2, and Rps3), and powdery mildew (rmd). The conserved N- or RPS2-homologous NBS sequences and their positional associations with mapped soybean-resistance genes suggest that a number of the soybean disease-resistance genes may belong to this superfamily. The candidate subfamilies of NBS-containing genes identified by genetic mapping should greatly facilitate the molecular cloning of disease-resistance genes.


Deployable micro-traps to sequester motile bacteria.
The development of strategies to reduce the load of unwanted bacteria is a fundamental challenge in industrial processing, environmental sciences and medical applications. Here, we report a new method to sequester motile bacteria from a liquid, based on passive, deployable micro-traps that confine bacteria using micro-funnels that open into trapping chambers. Even in low concentrations, micro-traps afford a 70% reduction in the amount of bacteria in a liquid sample, with a potential to reach >90% as shown by modelling improved geometries. This work introduces a new approach to contain the growth of bacteria without chemical means, an advantage of particular importance given the alarming growth of pan-drug-resistant bacteria.


Cln6 mutants associated with neuronal ceroid lipofuscinosis are degraded in a proteasome-dependent manner.
NCLs (neuronal ceroid lipofuscinoses), a group of inherited neurodegenerative lysosomal storage diseases that predominantly affect children, are the result of autosomal recessive mutations within one of the nine cln genes. The wild-type cln gene products are composed of membrane and soluble proteins that localize to the lysosome or the ER (endoplasmic reticulum). However, the destiny of the Cln variants has not been fully characterized. To explore a possible link between ER quality control and processing of Cln mutants, we investigated the fate of two NCL-related Cln6 mutants found in patient samples (Cln6(G123D) and Cln6(M241T)) in neuronal-derived human cells. The point mutations are predicted to be in the putative transmembrane domains and most probably generate misfolded membrane proteins that are subjected to ER quality control. Consistent with this paradigm, both mutants underwent rapid proteasome-mediated degradation and complexed with components of the ER extraction apparatus, Derlin-1 and p97. In addition, knockdown of SEL1L [sel-1 suppressor of lin-12-like (Caenorhabditis elegans)], a member of an E3 ubiquitin ligase complex involved in ER protein extraction, rescued significant amounts of Cln6(G123D) and Cln6(M241T) polypeptides. The results implicate ER quality control in the instability of the Cln variants that probably contributes to the development of NCL.


Tumor interaction with hemostasis: the rationale for the use of platelet inhibitors and anticoagulants in the treatment of cancer.
Clinical and experimental observations have firmly established the concept of a two-way interaction between malignancy and the hemostatic system. On the one hand, certain tumors can activate platelets and the coagulation mechanism in vivo, on the other, a convincing case has been made for the involvement of platelets and fibrin in tumor growth and metastasis. A large number of clinical and experimental studies have been conducted in order to test the efficacy of platelet inhibitors and anticoagulants as adjuvants in the treatment of cancer. Antiplatelet drugs gave variable results, depending on the drug and the tumor system tested. Prostaglandin synthetic pathways by both the host and tumor seem to be an important determinant in the response to platelet function inhibitors. Of the various anticoagulants tested, the coumarin derivatives gave somewhat consistent antitumor effect in certain human and experimental cancer. The antitumor effect of oral anticoagulants does not appear to be a primary drug effect and seems related to their role as vitamin K antagonists. It should be emphasized that although the antitumor potential of antithrombotic agents is a subject of keen interest at the present, their use in treating human cancer is still controversial.


Behavioral coping phenotypes and associated psychosocial outcomes of pregnant and postpartum women during the COVID-19 pandemic.
The impact of COVID-19-related stress on perinatal women is of heightened public health concern given the established intergenerational impact of maternal stress-exposure on infants and fetuses. There is urgent need to characterize the coping styles associated with adverse psychosocial outcomes in perinatal women during the COVID-19 pandemic to help mitigate the potential for lasting sequelae on both mothers and infants. This study uses a data-driven approach to identify the patterns of behavioral coping strategies that associate with maternal psychosocial distress during the COVID-19 pandemic in a large multicenter sample of pregnant women (N = 2876) and postpartum women (N = 1536). Data was collected from 9 states across the United States from March to October 2020. Women reported behaviors they were engaging in to manage pandemic-related stress, symptoms of depression, anxiety and global psychological distress, as well as changes in energy levels, sleep quality and stress levels. Using latent profile analysis, we identified four behavioral phenotypes of coping strategies. Critically, phenotypes with high levels of passive coping strategies (increased screen time, social media, and intake of comfort foods) were associated with elevated symptoms of depression, anxiety, and global psychological distress, as well as worsening stress and energy levels, relative to other coping phenotypes. In contrast, phenotypes with high levels of active coping strategies (social support, and self-care) were associated with greater resiliency relative to other phenotypes. The identification of these widespread coping phenotypes reveals novel behavioral patterns associated with risk and resiliency to pandemic-related stress in perinatal women. These findings may contribute to early identification of women at risk for poor long-term outcomes and indicate malleable targets for interventions aimed at mitigating lasting sequelae on women and children during the COVID-19 pandemic.


Three-dimensional Planning and Reconstruction of the Mandible in Children with Craniofacial Microsomia Type III Using Costochondral Grafts.
In craniofacial microsomia (CFM) Type III patients, autogenous costochondral grafts (CCG) are conventionally used for the reconstruction of the ramus and condyle. The aim of this study was to describe the use of CCG in children with CFM in terms of outcomes, growth patterns, and complications. This is a retrospective study of nine, aged 4-12 years, patients with CFM Type III, who underwent reconstruction of the mandibular ramus condyle unit by CCG. Seven patients had right-sided CFM and two had left-sided CFM. The rationale for this choice was to utilize the potential growth of the CCG, providing length to the ramus, and the joint by acting as a growth center; to control the repositioning of the chin center; and to improve child compliance by undergoing only one operation. The surgical treatment plan was determined preoperatively, based on measurements of mandibular vertical and horizontal deficiency and analysis of the mandibular posterior and anterior angulation. The mandibular planes and axis were defined by a three-dimensional simulation software program to perform a "mock surgery", by creating a prototype model. Clinical follow-up included measurements of the maximal opening, observation of the facial symmetry, and recording of complications, such as reankylosis. There were no serious postoperative complications, infections, or graft rejections. Successful postoperative occlusal cants were noted and measured in five patients and acceptable results were obtained in three patients. In one case, the CCG underwent distraction osteogenesis to improve the facial symmetry. In one patient, the graft continued to grow and the chin started to deviate into the opposite side. Measuring and calculating the ratio of the ramus height on the panoramic X-ray revealed a good relation between the healthy contralateral and the reconstructed ipsilateral ramus. Postoperative mean mouth opening was 34.3 mm, with minimal midline deviation of 2.6 mm in occlusion. Mean follow-up was 51.7 months. The mean postoperative occlusal cant analysis for eight patients was 3.66°. CCG is useful in treating CFM Type III. The growth potential of the CCG makes it the ideal choice for children. The advantages of this graft are its biological compatibility, workability, functional adaptability, and minimal additional detriment to the patient. The use of a stereolithographic model preoperatively improved intraoperative precision by clearly displaying detailed anatomy of the patient undergoing craniofacial surgery. The surgeon can plan the length of the CCG before surgery and use the printed template while harvesting without waiting for the exact measurements to be provided by the facial surgical team.


The Challenges of Big Data for Research Ethics Committees: A Qualitative Swiss Study.
Big data trends in health research challenge the oversight mechanism of the Research Ethics Committees (RECs). The traditional standards of research quality and the mandate of RECs illuminate deficits in facing the computational complexity, methodological novelty, and limited auditability of these approaches. To better understand the challenges facing RECs, we explored the perspectives and attitudes of the members of the seven Swiss Cantonal RECs via semi-structured qualitative interviews. Our interviews reveal limited experience among REC members with the review of big data research, insufficient expertise in data science, and uncertainty about how to mitigate big data research risks. Nonetheless, RECs could strengthen their oversight by training in data science and big data ethics, complementing their role with external experts and ad hoc boards, and introducing precise shared practices.


Clinical profile and predictors for outcome in children presenting with Guillain-Barré syndrome.
Acute Flaccid Paralysis (AFP) is a group of diverse clinical conditions with Guillain-Barré syndrome (GBS) as one of the most common cause. The aim of this study was to study the clinical features and predictors for the requirement of ventilation in children with GBS. This is a prospective observational study done at a tertiary care hospital where all consecutive children less than 15 years who presented with AFP were enrolled. Demographic characteristics, symptomatology, and physical findings of those patients who were diagnosed with GBS were recorded using a pre-defined questionnaire. Univariate analysis was done to identify clinical variables associated with a higher requirement of ventilation. Of a total of 53 children with AFP enrolled in the study, a total of 30 patients were diagnosed with GBS. A total of 12 (40%) patients required ventilation, while five of these patients eventually died. The following variants of GBS were identified: AIDP (13/30), AMAN (12/30), and ASMAN (2/30). Lower limbs were affected in 97% of the patients, whereas upper limbs were affected in 83% of the patients. Deep tendon reflexes of the upper limb and lower limb were preserved in 56% and 7% of the patients, respectively. Presence of antecedent URTI was associated with a lower requirement of ventilation. Presence of bulbar palsy, lower upper limb power on presentation, and absence of deep tendon reflex in upper limbs were associated with a higher requirement of ventilation. GBS is an important cause of AFP in India with no significant difference between the variants in terms of frequency and prognosis. Simple physical findings can be used by primary care physicians to predict the requirement of higher levels of care.


Plant traits linked to field-scale flammability metrics in prescribed burns in Eucalyptus forest.
Vegetation is a key determinant of wildfire behaviour at field scales as it functions as fuel. Past studies in the laboratory show that plant flammability, the ability of plants to ignite and maintain combustion, is a function of their traits. However, the way the traits of individual plants combine in a vegetation community to affect field flammability has received little attention. This study aims to bridge the gap between the laboratory and field by linking plant traits to metrics of field-scale flammability. Across three prescribed burns, in Eucalyptus-dominated damp and dry forest, we measured pre-burn plant species abundance and post-burn field flammability metrics (percentage area burnt, char and scorch height). For understory species with dominant cover-abundance, we measured nine traits that had been demonstrated to influence flammability in the laboratory. We used fourth-corner ordination to evaluate covariation between the plant traits, species abundance and flammability. We found that several traits covaried at the species level. In some instances, these traits (e.g. specific leaf area and bulk density) could have cumulative effects on the flammability of a species while in other instances (e.g. moisture and specific leaf area) they may have counteractive effects, assuming trait effects on flammability are akin to previous research. At field scales, species with similar traits tended to co-occur, suggesting that the effects of individual traits accumulate within a plant community. Fourth-corner analyses found the trait-field flammability relationship to be statistically significant. Traits significantly associated with increasing field flammability metrics were: bulk density (negatively associated) and hydrocarbon quantity, specific leaf area and surface area to volume ratio (all positively associated). Our study demonstrates that some traits known to influence flammability in the laboratory can be associated with field-scale flammability metrics. Further research is needed to isolate the contributions of individual traits to understand how species composition drives forest flammability.


Mold allergy: is it real and what do we do about it?
fungi produce substances that contain pathogen-associated molecular patterns (pamps) and damage-associated molecular patterns (damps) which bind to pattern recognition receptors, stimulating innate immune responses in humans. they also produce allergens that induce production of specific ige. Areas covered: In this review we cover both innate and adaptive immune responses to fungi. Some fungal products can activate both innate and adaptive responses and in doing so, cause an intense and complex health effects. Methods of testing for fungal allergy and evidence for clinical treatment including environmental control are also discussed. In addition, we describe controversial issues including the role of Stachybotrys and mycotoxins in adverse health effects. Expert commentary: Concerns about long-term exposure to fungi have led some patients, attorneys and fungus advocates to promote fears about a condition that has been termed toxic mold syndrome. This syndrome is associated with vague symptoms and is believed to be due to exposure to mycotoxins, though this connection has not been proven. Ultimately, more precise methods are needed to measure both fungal exposure and the resulting health effects. Once that such methods become available, much of the speculation will be replaced by knowledge.


Deletion of membrane-bound steel factor results in osteopenia in mice.
To examine the functional role of membrane-bound SLF, we evaluated the growing skeletons of WT and SLF mutant (Sl/Sl(d)) mice that do not produce this protein using DXA, bone histomorphometry, cell culture, and flow cytometry. Deletion of membrane-bound SLF delays bone growth, decreases bone mass and BMD, impairs osteoblast function, and increases osteoclast surface in young mice. Mutations at the murine steel locus lead to a defect in the development of hematopoietic stem cells, mast cells, and germ cells. Two isoforms of steel factor (SLF), soluble and membrane-associated, have been reported. Soluble SLF increases osteoclast formation and activity in cell culture. The effects of deletion of membrane-bound SLF on bone metabolism in mice have yet to be determined and are the subject of this study. Five-, 7-, and 12-week-old male and 5-week-old female WCB6F1/J-Kitl(Sl)/Kitl(Sl-d) (Sl/Sl(d)) mice and wildtype (WT) littermates were used. BMD and bone mass, growth, architecture, and turnover were evaluated by DXA (males and females) and histomorphometry (males only). Primary osteoblasts isolated from humeri of 5-week-old male WT and Sl/Sl(d) mice were used to determine osteoblast function, and bone marrow cells from tibias and femurs of these mice were analyzed to determine cell surface expression of osteoclast precursors. Young Sl/Sl(d) mice grew more slowly, had a reduced bone mass, and had shorter bones than WT littermates. Male mutants had significantly decreased whole body BMD in all age groups, largely because of a reduction in BMC. Tibial cross-sectional, cortical, and marrow area of cortical bone and cancellous bone volume was reduced in the mutants at all ages. The osteopenia in Sl/Sl(d) was caused by increased osteoclast surface at all ages and decreased osteoblast surface at 5 weeks of age. [(3)H]thymidine incorporation studies showed that proliferation of osteoblasts derived from mutant mice was significantly suppressed (56%). Moreover, a decrease in mineralization was observed in Sl/Sl(d) osteoblast culture. Fluorescence-activated cell sorting analysis of bone marrow cells from Sl/Sl(d) mice revealed a 65% increase in the percentage of c-Fms(+)CD11b(+)RANK(+) cells compared with WT controls. These findings suggest that membrane-bound SLF/c-Kit signaling plays a role in the regulation of peak bone mass.


Skin wounds in a rural setting of Côte d'Ivoire: Population-based assessment of the burden and clinical epidemiology.
Data on the burden and clinical epidemiology of skin wounds in rural sub-Saharan Africa is scant. The scale of the problem including preventable progression to chronic wounds, disability and systemic complications is largely unaddressed. We conducted a cross-sectional study combining active (household-based survey) and passive case finding (health services-based survey) to determine the burden and clinical epidemiology of wounds within the Taabo Health and Demographic Surveillance System (HDSS) in rural Côte d'Ivoire. Patients identified with wounds received free care and were invited to participate in the wound management study simultaneously carried out in the survey area. The data were analysed for wound prevalence, stratified by wound and patient characteristics. 3842 HDSS-registered persons were surveyed. Overall wound prevalence derived from combined active and passive case finding was 13.0%. 74.1% (403/544) of patients were below the age of 15 years. Most frequent aetiologies were mechanical trauma (85.3%), furuncles (5.1%), burns (2.9%) and Buruli ulcer (2.2%). Most wounds were acute and smaller than 5 cm2 in size. 22.0% (176/799) of wounds showed evidence of secondary bacterial infection. 35.5% (22/62) of chronic wounds had persisted entirely neglected for years. Buruli ulcer prevalence was 2.3 per 1000 individuals and considerably higher than expected from an annual incidence of 0.01 per 1000 individuals as reported by WHO for Côte d'Ivoire at the time of the study. Skin wounds are highly prevalent in rural West Africa, where they represent a widely neglected problem. The HDSS-based survey with combined active and passive case finding adopted in this study provides a better estimate than school- and health institution-based surveys which underestimate the frequency of skin wounds and, particularly, of neglected tropical diseases of the skin, such as Buruli ulcer and yaws. A comparison with country-specific WHO data suggests underreporting of Buruli ulcer cases. Registration at ClinicalTrials.gov NCT03957447.


Disrupted energy metabolism and neuronal circuit dysfunction in cognitive impairment and Alzheimer's disease.
Epidemiological, neuropathological, and functional neuroimaging evidence implicates global and regional disruptions in brain metabolism and energetics in the pathogenesis of cognitive impairment. Nerve cell microcircuits are modified by excitatory and inhibitory synaptic activity and neurotrophic factors. Ageing and Alzheimer's disease cause perturbations in cellular energy metabolism, level of excitation or inhibition, and neurotrophic factor release, which overwhelm compensatory mechanisms and result in dysfunction of neuronal microcircuits and brain networks. A prolonged positive energy balance impairs the ability of neurons to adapt to oxidative and metabolic stress. Results from experimental studies in animals show how disruptions caused by chronic positive energy balance, such as diabetes, lead to accelerated cognitive ageing and Alzheimer's disease. Therapeutic interventions to allay cognitive dysfunction that target energy metabolism and adaptive stress responses (such as neurotrophin signalling) have been effective in animal models and in preliminary studies in humans.


Trainees Associated with Improved Wait Times and Patient Satisfaction in a Multidisciplinary Clinic.
To determine variables associated with longer wait times and decreased patient satisfaction. To determine the association of trainees with clinic wait times and patient satisfaction scores in an academic center. Cross-sectional study. We recruited 266 study participants from an interdisciplinary Head and Neck Cancer outpatient clinic setting. Trained observers recorded observations related to wait times, time with individual health care practitioners, and total time spent in clinic. An 11-question survey was given to patients at the end of their visit assessing each patient's satisfaction with their visit, subjective wait time, and their likelihood to recommend the health care provider. Increased objective wait times were associated with new patients (p = 0.006) and based on the physician they saw (p < 0.001). Patients who saw a trainee spent less time waiting to see a physician (p = 0.023), more total time with a physician (p = 0.001), and reported higher wait time satisfaction scores (p = 0.001). There was no difference in total visit time if patients saw a trainee (p = 0.42). Patient satisfaction with wait time was correlated with all other aspects of patient satisfaction (p < 0.001). On multivariable analysis, the subjective wait time was associated with the likelihood to recommend (p < 0.001). Prolonged objective wait times in a multidisciplinary oncology outpatient setting were associated with several factors including specific physicians and new patient status. Trainee interaction with patients led to shorter wait times and improved patient satisfaction scores with wait times. Satisfaction with wait time was positively correlated with all aspects of patient satisfaction and 'likelihood to recommend' scores. NA Laryngoscope, 2023.


Effects of Lactobacillus plantarum A7 with probiotic potential on colon cancer and normal cells proliferation in comparison with a commercial strain.
Several beneficial effects have been attributed to the probiotic lactic acid bacteria. It was determined that lactobacilli can exert antiproliferative effects on the various cancer cell lines including colon cancer. Effects of lactic acid bacteria on colon cancer may vary from strain to strain and there is a need to find the new probiotic strains with tumor suppressing properties through in vitro studies. Anti-proliferative activities of heat-killed cells and cell-free supernatants of a native strain of Lactobacillus plantarum A7 and a commercial strain of lactobacillus rhamnosus GG were assessed on human colon cancer cell lines (Caco-2 and HT-29) and normal cells (L-929), using MTT assay. Cells were seeded at 2×10(4) cells/mlin 96 well plates and incubated for 24 hr. Then heat-killed cells (OD620: 0.025, 0.0.05, 0.1) and cell-free supernatants of bacteria were added at concentration of 2.5, 5 and 10 mg/ml. After 48 hr incubation MTT (5 mg/ml) was added and the absorbance was measured at 540 nm using ELISA plate reader. Results showed that heat-killed cells and cell-free supernatants of both probiotic strains reduced the growth rate of cancer and normal cells. These results suggested that anti-proliferative effect may not be an exclusive characteris ticwhich is dedicated to officially approved probiotics. L. plantarum A7 could be considered as colon cancer biological product, most likely due to its advantages in significant organic acid production.


Effects of upper thoracic manipulation on pressure pain sensitivity in women with temporomandibular disorder: a randomized, double-blind, clinical trial.
The aim of the present study was to evaluate the effects of upper thoracic manipulation on pain in subjects with temporomandibular disorder. Thirty-two women with a diagnosis of temporomandibular disorder were randomly allocated to an experimental group (n = 16), submitted to upper thoracic manipulation, and a placebo group (n = 16), submitted to a procedure in the thoracic region with no therapeutic effect. All volunteers underwent an evaluation of pain in the masticatory muscles and the temporomandibular joint using an algometer and the visual analog scale before and immediately after the procedure as well as after 48-72 hrs. Two-way repeated-measures analysis of variance was used for the intragroup and intergroup analyses, with the level of significance set to 5% (P < 0.05). Cohen d was calculated for the determination of the effect size. No significant group-by-time interaction was found (P > 0.05) for algometry in any analysis, and Cohen d revealed no significant effect of the treatment. Moreover, no significant group-by-time interaction was found for facial pain intensity determined using the visual analog scale (P > 0.05), and Cohen d also revealed no significant effect of the treatment regarding this variable. On the basis of the present findings, upper thoracic spinal manipulation does not lead to a reduction in pain in women with temporomandibular disorder.


Isolation of optically targeted single bacteria by application of fluidic force microscopy to aerobic anoxygenic phototrophs from the phyllosphere.
In their natural environment, bacteria often behave differently than they do under laboratory conditions. To gain insight into the physiology of bacteria in situ, dedicated approaches are required to monitor their adaptations and specific behaviors under environmental conditions. Optical microscopy is crucial for the observation of fundamental characteristics of bacteria, such as cell shape, size, and marker gene expression. Here, fluidic force microscopy (FluidFM) was exploited to isolate optically selected bacteria for subsequent identification and characterization. In this study, bacteriochlorophyll-producing bacteria, which can be visualized due to their characteristic fluorescence in the infrared range, were isolated from leaf washes. Bacterial communities from the phyllosphere were investigated because they harbor genes indicative of aerobic anoxygenic photosynthesis. Our data show that different species of Methylobacterium express their photosystem in planta, and they show a distinct pattern of bacteriochlorophyll production under laboratory conditions that is dependent on supplied carbon sources.


Atomic layer deposited tungsten nitride thin films as a new lithium-ion battery anode.
This article demonstrates the atomic layer deposition (ALD) of tungsten nitride using tungsten hexacarbonyl [W(CO)6] and ammonia [NH3] and its use as a lithium-ion battery anode. In situ quartz crystal microbalance (QCM), ellipsometry and X-ray reflectivity (XRR) measurements are carried out to confirm the self-limiting behaviour of the deposition. A saturated growth rate of ca. 0.35 Å per ALD cycle is found within a narrow temperature window of 180-195 °C. In situ Fourier transform infrared (FTIR) vibrational spectroscopy is used to determine the reaction pathways of the surface bound species after each ALD half cycle. The elemental presence and chemical composition is determined by XPS. The as-deposited material is found to be amorphous and crystallized to h-W2N upon annealing at an elevated temperature under an ammonia atmosphere. The as-deposited materials are found to be n-type, conducting with an average carrier concentration of ca. 10(20) at room temperature. Electrochemical studies of the as-deposited films open up the possibility of this material to be used as an anode material in Li-ion batteries. The incorporation of MWCNTs as a scaffold layer further enhances the electrochemical storage capacity of the ALD grown tungsten nitride (WNx). Ex situ XRD analysis confirms the conversion based reaction mechanism of the as-grown material with Li under operation.


Heterotrophic communities supplied by ancient organic carbon predominate in deep fennoscandian bedrock fluids.
The deep subsurface hosts diverse life, but the mechanisms that sustain this diversity remain elusive. Here, we studied microbial communities involved in carbon cycling in deep, dark biosphere and identified anaerobic microbial energy production mechanisms from groundwater of Fennoscandian crystalline bedrock sampled from a deep drill hole in Outokumpu, Finland, by using molecular biological analyses. Carbon cycling pathways, such as carbon assimilation, methane production and methane consumption, were studied with cbbM, rbcL, acsB, accC, mcrA and pmoA marker genes, respectively. Energy sources, i.e. the terminal electron accepting processes of sulphate-reducing and nitrate-reducing communities, were assessed with detection of marker genes dsrB and narG, respectively. While organic carbon is scarce in deep subsurface, the main carbon source for microbes has been hypothesized to be inorganic carbon dioxide. However, our results demonstrate that carbon assimilation is performed throughout the Outokumpu deep scientific drill hole water column by mainly heterotrophic microorganisms such as Clostridia. The source of carbon for the heterotrophic microbial metabolism is likely the Outokumpu bedrock, mainly composed of serpentinites and metasediments with black schist interlayers. In addition to organotrophic metabolism, nitrate and sulphate are other possible energy sources. Methanogenic and methanotrophic microorganisms are scarce, but our analyses suggest that the Outokumpu deep biosphere provides niches for these organisms; however, they are not very abundant.


Mortality displacement of heat-related deaths: a comparison of Delhi, São Paulo, and London.
Mortality increases with hot weather, although the extent to which lives are shortened is rarely quantified. We compare the extent to which short-term mortality displacement can explain heat deaths in Delhi, São Paulo, and London given contrasting demographic and health profiles. We examined time-series of daily mortality data in relation to daily ambient temperature using Poisson models and adjusting for season, relative humidity, rainfall, particulate air pollution, day of the week, and public holidays. We used unconstrained distributed lag models to identify the extent to which heat-related excesses were followed by deficits (mortality displacement). For each city, an increase in all-cause mortality was observed with same-day (lag 0) and previous day (lag 1) temperatures greater than a threshold of 20 degrees C. At lag 0, the excess risk was greatest in Delhi and smallest in London. In Delhi, an excess was apparent up to 3 weeks after exposure, after which a deficit was observed that offset just part of the overall excess. In London, the heat excess persisted only 2 days and was followed by deficits, such that the sum of effects was 0 by day 11. The pattern in São Paulo was intermediate between these. The risk summed over the course of 28 days was 2.4% (95% confidence interval = 0.1 to 4.7%) per degree greater than the heat threshold in Delhi, 0.8% (-0.4 to 2.1%) in São Paulo and -1.6% (-3.4 to 0.3%) in London. Excess risks were sustained up to 4 weeks for respiratory deaths in São Paulo and London and for children in Delhi. Heat-related short-term mortality displacement was high in London but less in Delhi, where infectious and childhood mortality still predominate.


Method to measure acoustic impedance and reflection coefficient.
A frequency-domain based system for measuring acoustic impedance and reflection coefficient is described. The calibration procedure uses a least-mean-squares approximation to the Thevenin parameters describing the source and receiver characteristics in which the data measured on closed, cylindrical tubes are matched to a viscothermal tube model. The system is intended for use in acoustical measurement in human ear canals, in which the cross-sectional area of the ear canal at the point of insertion is imprecisely known. This area is acoustically estimated from the impedance data, and the reflection coefficient is calculated in terms of this area and the impedance data. Measurements on a variety of closed tubes show the method is accurate over the frequency range investigated (less than 10.7 kHz). The time-domain reflection function is evaluated by transforming the reflection coefficient from the frequency domain, but the finite bandwidth of the measured data limits the accuracy of time-domain response measurements. The method is well suited for frequency-domain measurements in human ear canals.


Update on the management of abnormal uterine bleeding.
Abnormal uterine bleeding (AUB) is a common complaint that affects large numbers of women from puberty to menopause. It negatively affects health by causing anemia, and impacts the quality of life of women affected. AUB also has an economic impact for both women and society. Therefore, it should not be under- or overestimate and diagnosis, investigations and treatment should be proposed, taking into account the scientific data available in the current state of medical knowledge. Using the new terminology and etiologic classification of AUB is essential to communicate properly around the subject. The evaluation of the bleeding includes self-report and more objective methods. Work out should focus on diagnosing anemia and researching for causal factors. It is important to differentiate AUB caused by anatomical changes and functional causes, and the PALM-COIEN classification has been developed on that dichotomy. Investigations may include blood test, ultrasound, hysteroscopy and endometrial sampling is required in a certain number of situations. Treatment for AUB can be medical and/or surgical depending on the cause. Medical treatment is based on iron supplementation, hormonal and non-hormonal therapies. Surgical treatments include removal of a focal lesion, endometrial resection or destruction and hysterectomy. Age, desire for future pregnancy and etiology for AUB are key factors to consider before initiating a treatment. Treatment efficiency can be assessed using the same tools as pretherapeutic evaluation, and improvement of quality of life has now become the main goal for most international guidelines addressing the subject.


Maternal Age-Related Depletion of Offspring Genetic Variance in Immune Response to Phytohaemagglutinin in the Blue Tit (Cyanistes caeruleus).
Studies examining age-specific patterns in genetic variance have focussed primarily on changes in the genetic variance within cohorts. It remains unclear whether parental age may affect the genetic variance among offspring. To date, such an effect has been reported only in a single study performed in a wild bird population. Here, we provide experimental evidence that the additive genetic variance (VA) observed among offspring may be related to parental age in a wild passerine-the blue tit (Cyanistes caeruleus). To separate genetic and environmental components of phenotypic variance in nestling body size and immune function we cross-fostered nestlings between pairs of broods born to young and old mothers and used an animal model to estimate VA. We show that the genetic variance in immune response to phytohaemagglutinin (PHA) and body weight among offspring depends on maternal age. VA in response to PHA appeared to be lower among nestlings of older mothers. Such a tendency was not observed for tarsus length. We argue that the lower VA may result either from depletion of additive genetic variation due to selection acting on parents across age classes or from environmental effects confounded with parental age. Thus, our study suggests that parental age may significantly affect estimates of quantitative genetic parameters in the offspring.


Comparison of the α-amylase inhibitor-1 from common bean (Phaseolus vulgaris) varieties and transgenic expression in other legumes--post-translational modifications and immunogenicity.
The seeds of peas (Pisum sativum) and chickpeas (Cicer arietinum) expressing a gene for α-amylase inhibitor-1 (αAI) from the common bean (Phaseolus vulgaris) are protected from damage by old world bruchids (pea and cowpea weevils). Here, we used electrospray ionization time-of-flight mass spectrometry to compare the post-translational modifications of αAI from transgenic sources with the processed forms of the protein from several bean varieties. All sources showed microheterogeneity with differences in the relative abundance of particular variants due to differences in the frequency of addition of glycans, variable processing of glycans, and differences of C-terminal exopeptidase activity. The structural variation among the transgenics was generally within the range of the bean varieties. Previously, mice showed allergic reactions following ingestion of transgenic pea αAI but not bean αAI. Here, only minor differences were observed following intraperitoneal sensitization. Both of the transgenic pea and bean forms of αAI elicited Th1 and Th2 antibody isotype responses, suggesting that both proteins are immunogenic and could potentially be allergenic.


Idiopathic bile acid catharsis.
In the course of extensive routine screening for bile acid malabsorption a few patients were detected in whom chronic diarrhoea was apparently induced by excess bile acid loss which was neither associated with demonstrable conventional ileopathy nor with any other disorder allied to diarrhoea. In three patients subjected to scrutiny the results obtained were in harmony with a concept of idiopathic bile acid catharsis. Ingestion of cholestyramine was followed by immediate relief, but the diarrhoea recurred whenever this treatment was withdrawn. It it suggested that idiopathic bile acid catharsis should be suspected in patients with unexplained chronic diarrhoea and especially in those with a diagnosis of irritable colon with diarrhoea.


Morphologic and cytokine profile characterization of Salmonella enterica serovar typhimurium infection in calves with bovine leukocyte adhesion deficiency.
The role of neutrophils in the pathogenesis of Salmonella enterica Typhimurium-induced ruminant and human enteritis and diarrhea has yet to be characterized with in vivo models. To address this question, the in vivo bovine ligated ileal loop model of nontyphoidal salmonellosis was used in calves with the naturally occurring bovine leukocyte adhesion deficiency (BLAD) mutation whose neutrophils are unable to extravasate and infiltrate the extravascular matrix. Data obtained from 4 BLAD Holstein calves homozygous for BLAD (CD18-), 1 to 5 weeks of age, were compared with 4 controls, age-matched Holstein calves negative for BLAD (CD18+). Morphologic studies revealed that infection of CD18- calves with S Typhimurium resulted in no significant tissue infiltration by neutrophils, less tissue damage, reduced luminal fluid accumulation, and increased bacterial invasion, when compared with CD18+ calves. Ultrastructurally, lesions in enterocytes induced by S Typhimurium infection in CD18- calves--including attachment and disruption of the brush border, apical membrane ruffling formation, and cellular degeneration--were similar to the ones reported in the literature for CD18- calves. Study of cytokine gene expression by quantitative real-time polymerase chain reaction revealed that early stages of acute infection (4-8 hours postinfection) were associated with increased interleukin 8 gene expression in the absence of tissue influx of neutrophils in CD18- calves, whereas later stages of infection (12 hours postinfection) were associated with increased expression of growth-related oncogene alpha in the presence of neutrophil influx in CD18+ calves. In contrast, the proinflammatory cytokines interleukin 1beta and tumor necrosis factor alpha were poorly correlated with the presence or absence of tissue neutrophils.


[Progressive ataxia and distal muscular atrophy--differential diagnostic considerations on Roussy-Lévy syndrome].
The Roussy-Lévy-Syndrome ist generally considered a pheno-typic variant of the hereditary motor and sensory neuropathy type I (HMSN I), i.e. the classic Charcot-Marie-Tooth-neuropathy, and is thus nosographically distinguishable from Friedreich's ataxia. While posterior column symptomatology, dementia and rapid progression are recognized as diagnostic criteria for Friedreich's ataxia and HMSN I is clinically defined by the typical features of a progressive polyneuropathy, the symptom triad "gait disturbance, areflexia and pes cavus" of the Roussy-Lévy-Syndrome has comparatively little diagnostic specifity. Because of the variability of clinical symptoms as shown by two case reports, the diagnosis of Roussy-Lévy-Syndrome in childhood should be made only with great caution. For early genetic counselling and prognostic evaluation, bioptic and neurophysiologic results are of decisive importance.


Platelet activation by fMLP-stimulated polymorphonuclear leukocytes: the activity of cathepsin G is not prevented by antiproteinases.
Human polymorphonuclear leukocytes (PMN) activated by fMLP (in the presence of CaCl2, fibrinogen, and cytochalasin B) were able to induce aggregation, cytoplasmic Ca2+ increase, and thromboxane A2 production in coincubated autologousplatelets. Cell-free supernatants prepared from n-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated PMN were able also to induce platelet activation. Antibodies against cathepsin G and different serin protease inhibitors completely suppressed the activity of PMN-derived supernatants, indicating that cathepsin G is the major platelet activator released by PMN in our system. However, antiproteinases only partially affected platelet activation induced by PMN in mixed cell suspensions. Superoxide dismutase and catalase added to the cell suspension did not affect platelet activation nor potentiated serin protease inhibitors, making a role for short-lived oxygen radicals in our experimental system unlikely. Electron microscopic observation of stirred mixed cell suspensions preincubated for 2 minutes at 37 degrees C before stimulation showed a close PMN-platelets contact without any morphologic or biochemical event suggesting platelet activation. Preincubation of the cells without stirring to minimize PMN-platelet interaction before stimulation did not modify subsequent aggregation and platelet cytoplasmic Ca2+ increase in control samples. However, in this condition trypsin inhibitor from soybean completely prevented PMN-induced platelet activation. In samples preincubated without stirring in the presence of the antiproteinase, activated PMN stuck together but platelets preserved their discoid shape and did not appear significantly activated. We propose that membrane-to-membrane contact could create a microenvironment in which cathepsin G, discharged from stimulated PMN on adherent platelets, is protected from antiproteinases.


Thermal taste and anti-aspiration drugs: a novel drug discovery against pneumonia.
Despite the development of strong antibiotics, the pneumonia death is increasing all over the world in these decades. Among the people who died of pneumonia, the majority were 65 years old or over. Although pneumonia is recently categorized into several entities, aspiration pneumonia includes all entities. Therefore, targeting dysphagia and aspiration to treat pneumonia is a promising strategy and anti-aspiration drugs will be a part of pneumonia treatment. The swallowing reflex in elderly people was temperature-sensitive and the improvement of swallowing reflex by temperature stimuli could be mediated by the thermosensing TRP channels at pharynx. The administration of capsaicin as an agonist stimulus of TRPV1, a warm temperature receptor, decreased the delay in swallowing reflex. Red wine polyphenols improved swallowing reflex by enhancing TRPV1 response. Food with menthol, agonist of TRPM8 which is a cold temperature receptor, also decreased the delay in swallowing reflex. Olfactory stimulation such as black pepper was useful to improve the swallowing reflex for people with low ADL levels or with decreased consciousness. Thus, recent advancement of geriatrics found several anti-aspiration drugs such as thermosensing TRP channel agonists, black pepper odor, amantadine, cilostazol, theophylline and angiotensin- converting enzymes inhibitors. Thermosensing TRP channel agonists include capsaicin, capsiate, menthol, and red wine polyphenols. Controls of swallowing are mediated by various stages of neural system from peripheral sensory nerves to the entire cerebral cortex. Each anti-aspiration drug acts on various sites of neural axis of swallowing reflex. The combination of various anti-aspiration drugs may improve dysphagia and prevent aspiration pneumonia.


Ferrets (Mustela putoius furo) inefficiently convert beta-carotene to vitamin A.
The ferret has recently been used as a model to evaluate the absorption and metabolism of several carotenoids; however, little is known about the vitamin A (VA) requirements of this species or the ability of ferrets to convert dietary beta-carotene (betaC) to VA. Three studies were conducted to estimate the daily utilization of VA in ferrets and to determine the effect of prior VA status on the ability of ferrets to utilize betaC as a source of VA. Weanling male ferrets were fed a pelleted, low carotenoid, semipurified diet either with (+VA) or without VA (-VA) for 21- to 35-d prefeeding periods. Upon initiation of the experiments, several ferrets were killed to determine base-line VA status. The remaining ferrets were fed VA, betaC, or VA and betaC in pelleted feed (Studies 1-3) or liquid carrier (Study 3) for 16-21 additional days. Hepatic VA and betaC concentrations were used as the primary indicators of VA status, although serum and adrenal VA and betaC also were measured. The results showed the following: 1) provision of betaC at up to a 15:1 weight ratio of betaC to VA in pelleted feed or liquid carrier was not sufficient to maintain hepatic VA stores after a -VA prefeeding period; 2) the daily utilization rate of VA by ferrets ranged from 80 to 171 microg in the three studies; 3) the ferret was confirmed to be a species that has the majority of its serum VA in ester form; and 4) feeding -VA diets significantly reduced serum retinyl esters but had less effect on serum retinol. We conclude that although ferrets can convert betaC to VA, the process is inefficient. The ferret model can be most appropriately used when studying the biological effect of tissue betaC stores on VA status and is less appropriate for the evaluation of dietary betaC conversion to VA.


[Two patterns of Ct-brain perfusion and Dc-potentials of the brain evoked cognitive task in discirculatory encephalopathy patients].
In patients with discirculatory encephalopathy the influence of verbal fluency test on the characteristics of cerebral perfusion, DC-potentials of the brain, as well as on blood pressure and heart rate was investigated. Two patterns of responses to the verbal fluency test were observed. The first one is the process of generalized activation, manifested by the reduction of the TTP (time to peak) parameters of brain perfusion, the rise of the DC-potentials in all areas of brain and the modulation of blood pressure and heart rate. The second process, directly connected with cognitive processing, was manifested by the shifts of local characteristics of brain perfusion and DC-potentials in the frontal, temporal and central cortex, especially in the left hemisphere. Correlations were found between the characteristics of cerebral perfusion and DC-potentials on the one hand and the number of words during the verbal fluency test performance on the other hand.


Socioeconomic status and health among older adults in Thailand: an examination using multiple indicators.
A survey of 14,000 Thais, 50 and older, is utilized to test hypotheses about the association between socioeconomic status (SES) and health previously derived through observation of Western populations. Central among hypotheses is the notion that an inverse association can be uniformly detected across a matrix of SES indicators and health outcomes. Indicators of SES in this study include the traditional education, occupation and income measures, and a measure of household possessions. This later indicator may be particularly useful in a non-Western setting such as Thailand. Health outcomes were derived in order to represent a subjective, a social, and a medical conceptualization of health and included measures for self-assessed health, functional disorders and chronic health conditions. All health indicators were dichotomously coded as existence or non-existence. Also tested are associations throughout ordered categories of SES. Results generally support hypotheses. Unadjusted for other SES covariates, all four indicators of status strongly related to two of the three health measures, when controlling for other important covariates. When adjusted for each other, a number of the associations remained strong. There were also several notable exceptions. Little association existed between SES and chronic health disorders. The results may serve to highlight the distinct social environment acting upon the association.


[Hip diseases in pregnancy].
Transient osteoporosis and avascular femoral head necrosis represent rare but typical complications in the third trimenon of pregnancy. On the basis of five cases we report on the diagnosis, course and treatment of these diseases which are rarely mentioned in German literature.


Associations Between Parenting Behaviors and Behavioral Problems in Young Children With Developmental Delays.
Children with developmental delays (DD) are at heightened risk for developing behavior problems, which contribute to parenting stress and caregiving burden. There is an established relation between parenting behaviors and child developmental outcomes with less known about parent-child interactions in young children with DD. The present study examined the associations between parenting behaviors and child behavior in a sample of 180 families with preschool-aged children with DD. Results indicated that caregivers' harsh and coercive behaviors were associated with observed challenging behavior in children. Child age, as well as the number of commands issued by caregivers were associated with noncompliance in children. The significance and limitations of these findings are discussed, as well as recommendations for interventions and future research.


Perianal Crohn's disease: is there something new?
Perianal lesions are common in patients with Crohn's disease, and display aggressive behavior in some cases. An accurate diagnosis is necessary for the optimal management of perianal lesions. Treatment of perianal Crohn's disease includes medical and/or surgical options. Recent discoveries in the pathogenesis of this disease have led to advances in medical and surgical therapy with good results. Perianal lesions in Crohn's disease remain a challenging aspect for both gastroenterologists and surgeons and lead to a greatly impaired quality of life for all patients affected by this disease. A multidisciplinary approach is mandatory to obtain the best results.


[Mechanisms of development of recurrences in endogenous psychoses. Duration of remission in affective psychoses].
A study was made of 755 remissions in 171 patients suffering from affective psychoses. It has been established that distributions of the duration of complete remissions designed according to small (week and two-week) intervals are of periodic nature. This attests to rhythmical fluctuations of the risk of a relapse. Mathematic methods of analysis of the time series enable one to establish the polyrhythmic structure of the fluctuations, in which the leading rhythms are those with the intervals lengths of the order of 2, 5, 9, 12-13 and 22 weeks. These data well agree on the whole with the findings obtained earlier for schizophrenia remissions.