Detection of circulating breast cancer cells by reverse transcriptase polymerase chain reaction (RT-PCR).
The confounding problem in treatment of breast cancer is the metastasis of breast tumour. Reverse transcriptase polymerase chain reaction (RT-PCR) has been recently used in the detection of circulating breast cancer cells. This review reports on the development of this assay as well as its advantages and disadvantages. We feel that cytokeratin 20 and beta -human chorionic gonadotropin (hCG) mRNA are the best markers for the detection of circulating breast cancer cells. We suggest that the multiple RNA marker RT-PCR assay can help to increase both sensitivity and specificity of detection, and that quantitative RT-PCR assay is more effective than the qualitative assay in the detection of circulating breast cancer cells.


Picosecond protein dynamics: the origin of the time-dependent spectral shift in the fluorescence of the single Trp in the protein GB1.
How a biological system responds to a charge shift is a challenging question directly relevant to biological function. Time-resolved fluorescence of a tryptophan residue reflects protein and solvent response to the difference in pi-electron density between the excited and the ground state. In this study we use molecular dynamics to calculate the time-dependent spectral shift (TDSS) in the fluorescence of Trp-43 in GB1 protein. A new computational method for separating solvent, protein, and fluorophore contributions to TDSS is applied to 100 nonequilibrium trajectories for GB1 in TIP3P water. The results support several nontrivial conclusions. Both longitudinal and transverse relaxation modes of bulk solvent contribute to the TDSS in proteins. All relaxation components slower than the transverse relaxation of bulk solvent have significant contributions from both protein and solvent, with a negative correlation between them. Five exponential terms in the TDSS of GB1 are well separated by their relaxation times. A 0.036 ps term is due to both solvent (60%) and protein (40%). Two exponential terms represent longitudinal (tau(L) approximately = 0.4 ps) and transverse (tau(D) approximately = 5.6 ps) relaxation modes of TIP3P water. A 131 ps term is attributable to a small change in the tertiary structure, with the alpha-helix moving 0.2 A away from the beta-strand containing Trp-43. A 2580 ps term is due to the change in the conformation of the Glu-42 side chain that brings its carboxyl group close to the positively charged end of the excited fluorophore. Interestingly, water cancels 60% of the TDSS resulting from this conformational change.


Outcome of endovascular therapy in stroke with large vessel occlusion and mild symptoms.
To compare outcomes after endovascular therapy (EVT) and IV thrombolysis (IVT) in patients with stroke with emergent large vessel occlusion (LVO) and mild neurologic deficits. This was a retrospective analysis of patients from the Swiss Stroke Registry with admission NIH Stroke Scale score ≤5 and LVO treated by EVT (± IVT) vs IVT alone. The primary endpoint was favorable functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months. Secondary outcomes were independence (mRS score 0-2), mRS score (ordinal shift analysis), and survival with high disability (mRS score 4-5). Safety endpoints were mortality and symptomatic hemorrhage. Of 11,356 patients, 312 met the criteria and propensity score method matched 108 in each group. A comparably large proportion of patients with EVT and IVT had favorable outcome (63% vs 65.7% respectively; odds ratio 0.94, 95% confidence interval 0.51-1.72; p = 0.840). Patients with EVT showed a nonsignificant trend toward higher mRS score at 3 months (p = 0.717), while the proportion of surviving patients with high disability was comparably very low in both groups (p = 0.419). Mortality was slightly higher among those with EVT (9.3% vs 2.8%; p = 0.06), and symptomatic intracranial hemorrhage was a rare event in both groups (2.8% vs 0%; p = 0.997). In acute ischemic stroke, EVT and IVT appear similarly effective in achieving favorable outcome at 3 months for patients with LVO and mild neurologic symptoms. EVT might be marginally inferior to IVT regarding outcome across all levels of disability and mortality. Further studies are required to determine whether certain subgroups of patients with LVO and mild symptoms benefit from EVT. This study provides Class III evidence that patients with LVO and mild symptoms receiving either EVT or IVT had similar favorable functional outcomes at 3 months.


Use of an 'evidence-based implementation' strategy to implement evidence-based care of asthma into rural district hospital emergency departments.
To determine if an evidence-based implementation (EBI) could lead to the successful implementation of evidence based care for adult asthma in small rural district hospitals. A controlled trial involving eight small rural hospitals (four each in the study and control groups) was conducted. Retrospective pre-intervention audits were conducted at all eight hospitals for 7 months (1 January 2004 to 31 July 2004) and evidence-practice gaps identified. An EBI was then used to implement established guidelines for the management of asthma in the study hospitals. Post-intervention audits were then performed over a period of 7 months (1 October 2004 to 31 April 2005). There were 52 presentations of asthma in the study hospitals in the pre-implementation phase and 47 post-implementation. The corresponding numbers for the control hospitals were 46 and 42 respectively. There were no statistically significant differences in the severity between the groups. Following the EBI there were significant improvements at the study hospitals for the documentation of severity (8% to 62%, p <0.001), use of spirometry (12% to 62%, p <0.001) and the use of written short-term asthma plans (9% to 26%, p = 0.05). There was a decrease in use of ipratropium in mild asthma (44% to 30%, p = 0.228), an increase in the use of systemic steroids (61% to 72%, p = 0.255) and no change in prescribing antibiotics for afebrile patients with asthma (21% to 21% p = 0.956). There was no significant change in practice at the control hospitals except for a decrease in the use of systemic steroids (48% to 21%, p = 0.011). For the six clinical indicators aggregate there was a significant increase in compliance with guidelines at the study hospitals (36% to 62%, p < 0.001) but no change at the control hospitals (31% to 31%, p = 0.970). The pre-intervention audits demonstrated low levels of compliance with asthma guidelines across six clinical indicators. An EBI significantly improved compliance across these six indicators, and no improvement was noted in the control hospitals. This study demonstrates that an EBI can alter clinical practice in small rural district hospitals.


Effects of a personal trainer and financial incentives on exercise adherence in overweight women in a behavioral weight loss program.
Exercise is important for long-term weight loss, but few studies have examined ways to improve exercise adherence in overweight subjects participating in a behavioral weight loss program. This paper presents two studies, one conducted at the University of Pittsburgh and one at the University of Minnesota, that sought to improve exercise adherence by exerting more direct control over the environmental antecedents and consequences controlling exercise. Study 1 investigated the use of a personal trainer who called participants regularly and met them at their home or office at scheduled times for a walk. Study 2 investigated the effect of a lottery incentive for exercise adherence. In both studies, the effect of these manipulations was examined in the context of a 24-week standard behavioral weight control program with three supervised exercise sessions per week. Neither intervention achieved statistically significant improvements in exercise adherence compared to control conditions, perhaps due in part to the limited statistical power of the studies. Future studies should focus on better understanding the barriers to exercise and designing behavioral interventions that address these barriers.


Time courses of post-injury mitochondrial oxidative damage and respiratory dysfunction and neuronal cytoskeletal degradation in a rat model of focal traumatic brain injury.
Traumatic brain injury (TBI) results in rapid reactive oxygen species (ROS) production and oxidative damage to essential brain cellular components leading to neuronal dysfunction and cell death. It is increasingly appreciated that a major player in TBI-induced oxidative damage is the reactive nitrogen species (RNS) peroxynitrite (PN) which is produced in large part in injured brain mitochondria. Once formed, PN decomposes into highly reactive free radicals that trigger membrane lipid peroxidation (LP) of polyunsaturated fatty acids (e.g. arachidonic acid) and protein nitration (3-nitrotyrosine, 3-NT) in mitochondria and other cellular membranes causing various functional impairments to mitochondrial oxidative phosphorylation and calcium (Ca2+) buffering capacity. The LP also results in the formation of neurotoxic reactive aldehyde byproducts including 4-hydroxynonenal (4-HNE) and propenal (acrolein) which exacerbates ROS/RNS production and oxidative protein damage in the injured brain. Ultimately, this results in intracellular Ca2+ overload that activates proteolytic degradation of α-spectrin, a neuronal cytoskeletal protein. Therefore, the aim of this study was to establish the temporal evolution of mitochondrial dysfunction, oxidative damage and cytoskeletal degradation in the brain following a severe controlled cortical impact (CCI) TBI in young male adult rats. In mitochondria isolated from an 8 mm diameter cortical punch including the 5 mm wide impact site and their respiratory function studied ex vivo, we observed an initial decrease in complex I and II mitochondrial bioenergetics within 3 h (h). For complex I bioenergetics, this partially recovered by 12-16 h, whereas for complex II respiration the recovery was complete by 12 h. During the first 24 h, there was no evidence of an injury-induced increase in LP or protein nitration in mitochondrial or cellular homogenates. However, beginning at 24 h, there was a gradual secondary decline in complex I and II respiration that peaked at 72 h. post-TBI that coincided with progressive peroxidation of mitochondrial and cellular lipids, protein nitration and protein modification by 4-HNE and acrolein. The oxidative damage and respiratory failure paralleled an increase in Ca2+-induced proteolytic degradation of the neuronal cytoskeletal protein α-spectrin indicating a failure of intracellular Ca2+ homeostasis. These findings of a surprisingly delayed peak in secondary injury, suggest that the therapeutic window and needed treatment duration for certain antioxidant treatment strategies following CCI-TBI in rodents may be longer than previously believed.


Diagnosing functional abdominal pain with the Rome II criteria: parent, child, and clinician agreement.
To compare the Rome II diagnoses made in children with recurrent abdominal pain by physicians and by parent and child responses on the Questionnaire on Pediatric Gastrointestinal Symptoms. Rates of diagnostic agreement and reasons for disagreement were examined to determine whether changes to the Rome II criteria are needed to improve diagnostic classification. One hundred and forty-eight children and their parents or guardians completed the Questionnaire on Pediatric Gastrointestinal Symptoms during their first visit to a pediatric gastroenterology clinic. Parent- and child-report Rome II diagnoses were based on Questionnaire on Pediatric Gastrointestinal Symptoms scoring criteria, whereas the physician's Rome II diagnosis was based on clinical impression from history and physical examination completed at this visit. Statistical comparisons involved Pearson chi tests and Fisher exact tests. Kappa and weighted kappa measured agreement rates. Most children met the criteria for a functional gastrointestinal disorder based on the Rome II criteria. Functional dyspepsia was the most common diagnosis made by all three sources. The percentage of children classified as "no diagnosis" was small and was often a function of symptom duration (especially when diagnosis rested on the child self-report). Diagnostic agreement was fair to moderate. Diagnoses based on parent and child questionnaires agreed more often on functional dyspepsia than irritable bowel syndrome. Diagnostic disagreement was most likely to result from parent and child disagreement on defecation symptoms. The Rome II classification system shows promise for improving diagnosis, study and treatment of children with recurrent abdominal pain. However, further refinement and clarification of the Rome II criteria for symptom duration and frequency may be needed to improve diagnostic agreement.


Actinic skin damage and mortality--the First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study.
Exposure to sunlight may decrease the risk of several diseases through the synthesis of vitamin D, whereas solar radiation is the main cause of some skin and eye diseases. However, to the best of our knowledge, the association of sun-induced skin damage with mortality remains unknown. Subjects were 8472 white participants aged 25-74 years in the First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. Cardiovascular disease mortality, cancer mortality, and all-cause mortality were obtained by either a death certificate or a proxy interview, or both. Actinic skin damage was examined and recorded by the presence and severity (absent, minimal, moderate, or severe) of overall actinic skin damage and its components (i.e., fine telangiectasia, solar elastosis, and actinic keratoses). Cox regression and Kaplan-Meier methods were applied to explore the associations. A total of 672 cancer deaths, 1500 cardiovascular disease deaths, and 2969 deaths from all causes were documented through the follow-up between 1971 and 1992. After controlling for potential confounding variables, severe overall actinic skin damage was associated with a 45% higher risk for all-cause mortality (95% CI: 1.22, 1.72; P<0.001), moderate overall skin damage with a 20% higher risk (95% CI: 1.08., 1.32; P<0.001), and minimal overall skin damage with no significant mortality difference, when compared to those with no skin damage. Similar results were obtained for all-cause mortality with fine telangiectasia, solar elastosis, and actinic keratoses. The results were similar for cancer and cardiovascular disease mortality. The present study gives an indication of an association of actinic skin damage with cardiovascular disease, cancer and all-cause mortality in white subjects. Given the lack of support in the scientific literature and potential unmeasured confounding factors, this finding should be interpreted with caution. More independent studies are needed before any practical recommendations can be made.


The impact of proximal fibula fractures in the prognosis of tibial plateau fractures: a novel classification.
Fifty-five patients who presented with the complaint of tibia plateau fractures between January 1998 and November 2001 were retrospectively evaluated. The evaluation was based on their treatment modality. Twenty-five conservatively-treated patients (group 1) and 30 surgically-treated patients (group 2) were evaluated. In group 1, seven patients with proximal fibula fractures had lateral hamstring tightness. Five out of these seven patients had concomitant lateral knee pain. Similarly, nine patients with proximal fibula fractures in group 2 had lateral hamstring tightness, and seven patients in the same group suffered from lateral knee pain. The patients with no fibula proximal fracture in both groups had no hamstring tightness or lateral knee pain. The proximal fibula in the knee joint and its anatomical structures are of utmost importance for the anatomical integrity of the knee and its normal functions. The fibula has rich anatomical relations, some of which are important structures of the knee. These anatomical structures and the fibula provide stability of the knee joint and its functions as well as being an important mechanical support to the knee joint. Therefore, the knee joint will receive the negative effects from the pathologies of the bone or soft tissue that may occur in fibula fractures.


Building human capacity through early childhood intervention: the Child Development Research Programme at the Tropical Medicine Research Institute, the University of the West Indies, Kingston, Jamaica.
Research conducted by the Child Development Research Group in the Tropical Medicine Research Institute has made significant contributions to the understanding of the importance of early nutrition and the home environment for children's development and the impact of psychosocial stimulation for disadvantaged and/or undernourished children. The work has provided critical evidence that has contributed to the increasing attention given to early childhood development in the work and policies of agencies such as the World Bank, World Health Organization (WHO) and United Nations Children Fund (UNICEF). This review concerns research which documented the impact of malnutrition on children's development and for the first time demonstrated the benefits and necessity of psychosocial stimulation for improvement in development. Subsequent research was critical in establishing the importance of linear growth retardation (stunting) as a risk factor for poor child development. A twenty-two-year study of stunted children has demonstrated benefits through to adulthood in areas such as educational attainment, mental health and reduced violent behaviour from an early childhood home visiting programme that works through mothers to promote their children's development. The group's research has also demonstrated that it is feasible and effective to integrate the stimulation intervention into primary care services with benefits to children's development and mothers'child rearing knowledge and practices. The group is currently conducting a study to provide information needed for scaling-up of parenting programmes through evaluation of a new approach to improving parenting through health centres and a modified home visit programme.


Gender separation increases somatic growth in females but does not affect lifespan in Nothobranchius furzeri.
According to life history theory, physiological and ecological traits and parameters influence an individual's life history and thus, ultimately, its lifespan. Mating and reproduction are costly activities, and in a variety of model organisms, a negative correlation of longevity and reproductive effort has been demonstrated. We are employing the annual killifish Nothobranchius furzeri as a vertebrate model for ageing. N. furzeri is the vertebrate displaying the shortest known lifespan in captivity with particular strains living only three to four months under optimal laboratory conditions. The animals show explosive growth, early sexual maturation and age-dependent physiological and behavioural decline. Here, we have used N. furzeri to investigate a potential reproduction-longevity trade-off in both sexes by means of gender separation. Though female reproductive effort and offspring investment were significantly reduced after separation, as investigated by analysis of clutch size, eggs in the ovaries and ovary mass, the energetic surplus was not reallocated towards somatic maintenance. In fact, a significant extension of lifespan could not be observed in either sex. This is despite the fact that separated females, but not males, grew significantly larger and heavier than the respective controls. Therefore, it remains elusive whether lifespan of an annual species evolved in periodically vanishing habitats can be prolonged on the cost of reproduction at all.


Racial and socioeconomic disparities in parkinsonism.
To assess potential racial and socioeconomic disparities in patients with parkinsonism treated at a tertiary Movement Disorders Center. Patients with parkinsonism were evaluated for demographics (age, race, annual income, and educational level), medical comorbidities, medication regimen, disability (Older Americans Resources and Services subscale), presence of Parkinson disease, and disease severity (Unified Parkinson Disease Rating Scale). Disability and disease severity measures were compared by race, income, and educational level using analysis of variance for continuous variables and χ(2) tests for dichotomous variables. The sample included 1159 patients with parkinsonism (93.4% white, 6.1% African American, 61.2% who earned more than $50,000 annually, 62.7% who completed college, and 79.2% with a diagnosis of Parkinson disease). Cross-sectional analyses by race, income, and educational level showed greater disability and disease severity in African American compared with white patients (African American vs white Older Americans Resources and Services subscale total score, 29.8 vs 25.3, P = .005; Unified Parkinson's Disease Rating Scale total score, 53.0 vs 42.8; P < .001). African Americans were less likely to be prescribed dopaminergic medications, particularly newer agents (African Americans 20.6% vs whites: 41.1%; P = .01). Lower income and lower educational level were independently associated with greater disease severity and disability (P < .003). Racial and socioeconomic disparities exist among patients with parkinsonism being treated at a tertiary Movement Disorders Center. African Americans and those with lower socioeconomic status have greater disease severity and disability than whites. These disparities may be because of problems in diagnosis, access to care, physician referrals, and patient attitudes regarding the appropriate threshold for seeking treatment at a specialized center. Understanding and correction of these disparities may improve outcomes.


Comparison of virtual to true unenhanced abdominal computed tomography images acquired using rapid kV-switching dual energy imaging.
To compare "virtual" unenhanced (VUE) computed tomography (CT) images, reconstructed from rapid kVp-switching dual-energy computed tomography (DECT), to "true" unenhanced CT images (TUE), in clinical abdominal imaging. The ability to replace TUE with VUE images would have many clinical and operational advantages. VUE and TUE images of 60 DECT datasets acquired for standard-of-care CT of pancreatic cancer were retrospectively reviewed and compared, both quantitatively and qualitatively. Comparisons included quantitative evaluation of CT numbers (Hounsfield Units, HU) measured in 8 different tissues, and 6 qualitative image characteristics relevant to abdominal imaging, rated by 3 experienced radiologists. The observed quantitative and qualitative VUE and TUE differences were compared against boundaries of clinically relevant equivalent thresholds to assess their equivalency, using modified paired t-tests and Bayesian hierarchical modeling. Quantitatively, in tissues containing high concentrations of calcium or iodine, CT numbers measured in VUE images were significantly different from those in TUE images. CT numbers in VUE images were significantly lower than TUE images when calcium was present (e.g. in the spine, 73.1 HU lower, p < 0.0001); and significantly higher when iodine was present (e.g. in renal cortex, 12.9 HU higher, p < 0.0001). Qualitatively, VUE image ratings showed significantly inferior depiction of liver parenchyma compared to TUE images, and significantly more cortico-medullary differentiation in the kidney. Significant differences in VUE images compared to TUE images may limit their application and ability to replace TUE images in diagnostic abdominal CT imaging.


Immediate acoustic effects of straw phonation exercises in subjects with dysphonic voices.
Abstract This study sought to measure any acoustic changes in the speaking voice immediately after phonation exercises involving plastic straws versus phonation exercises with the open vowel /a/. Forty-one primary school teachers with slightly dysphonic voices were asked to participate in four phonatory tasks. Phonetically balanced text at habitual intensity level and speaking fundamental frequency was recorded. Acoustical analysis with long-term average spectrum was performed. Significant changes after therapy for the experimental group include the alpha ratio, L1-L0 ratio and ratio between 1-5 kHz and 5-8 kHz. The results indicate that the use of phonatory tasks with straw exercises can have immediate therapeutic acoustic effects in dysphonic voices. Long-term effects were not assessed in this study.


Spectral-domain optical coherence tomography appearance of a retinal nematode.
A 65-year-old man presented with decreased visual acuity in his left eye of 10 days' duration. Ocular examination revealed visual acuity of 20/200 in the left eye caused by a visible retinal nematode (roundworm) located close to the fovea. Spectral-domain optical coherence tomography imaging showed the nematode in the retinal nerve fiber layer. The patient was followed up without treatment, and the nematode disappeared spontaneously after 5 weeks. Visual acuity in the affected eye improved to 20/25.


Using women's health research to develop women leaders in academic health sciences: the National Centers of Excellence in Women's Health.
While the number of women entering U.S. medical schools has risen substantially in the past 25 years, the number of women in leadership positions in academic medicine is disproportionately small. The traditional pathway to academic leadership is through research. Women's health research is an ideal venue to fill the pipeline with talented women physicians and scientists who may become academic leaders in positions where they can promote positive change in women's health as well as mentor other women. The Office on Women's Health (OWH) in the U.S. Department of Health and Human Services has contracted with 18 academic medical centers to develop National Centers of Excellence in Women's Health. Emphasizing the integral link between women's health and women leaders, each of the Centers of Excellence must develop a leadership plan for women in academic medicine as part of the contract requirements. This paper describes the training programs in women's health research that have developed at five of the academic medical centers: the University of Wisconsin, Magee Women's Hospital, the University of Maryland, Medical College of Pennsylvania Hahnemann University, and the University of Illinois at Chicago. We discuss some of the challenges faced for both initiation and future viability of these programs as well as criteria by which these programs will be evaluated for success.


Experimental nonsurgical tattoo removal in a guinea pig model with topical imiquimod and tretinoin.
Tattoo removal is a common request in dermatologic surgery practices. Conventional tattoo removal modalities consist of mechanical, chemical, and thermal methods, but these interventions may result in undesirable dermal damage, disfiguring scars, and pigmentary changes. To evaluate the efficacy of topical imiquimod and tretinoin for the removal of tattoos in a guinea pig model. Five albino guinea pigs (A-E) were tattooed with black, red, green, and yellow. Beginning 6 hours after tattooing, A received no treatment, B was treated with petrolatum, C had imiquimod cream alternating with tretinoin gel, D had imiquimod cream alone, and E received tretinoin gel alone. The animals were treated for 7 days. Biopsies of the tattoos were taken at 6 hours, 7 days, and 28 days. Control guinea pig B had normal-appearing tattoos with consistent histopathology on day 28. Guinea pig D, treated with imiquimod cream clinically, had no visible tattoo, consistent with greatly diminished or no dye evident on histopathology. Guinea pig E, treated with tretinoin gel, and guinea pig C, treated with combination tretinoin gel and imiquimod cream, had faded tattoos and moderate clearance of pigment on histopathology. In the guinea pig, the use of imiquimod was successful as a nonsurgical method of acute-phase tattoo removal, but was associated with fibrosis and the loss of dermal appendages.


Constructing exact representations of quantum many-body systems with deep neural networks.
Obtaining accurate properties of many-body interacting quantum matter is a long-standing challenge in theoretical physics and chemistry, rooting into the complexity of the many-body wave-function. Classical representations of many-body states constitute a key tool for both analytical and numerical approaches to interacting quantum problems. Here, we introduce a technique to construct classical representations of many-body quantum systems based on artificial neural networks. Our constructions are based on the deep Boltzmann machine architecture, in which two layers of hidden neurons mediate quantum correlations. The approach reproduces the exact imaginary-time evolution for many-body lattice Hamiltonians, is completely deterministic, and yields networks with a polynomially-scaling number of neurons. We provide examples where physical properties of spin Hamiltonians can be efficiently obtained. Also, we show how systematic improvements upon existing restricted Boltzmann machines ansatze can be obtained. Our method is an alternative to the standard path integral and opens new routes in representing quantum many-body states.


Immunologic methods of purging in autologous stem cell transplantation.
Malignant cells in the stem cell product have been shown to contribute to disease recurrence in patients who relapse after autologous transplantation. Immunologic methods of purging tumor cells from stem cell products focus on either removal of specific target cells or positive selection of HPC. mAb are the key component of many purging strategies and are employed both in vitro and in vivo. Cytotoxic cellular therapies are an emerging method of tumor cell eradication.


Development of an immunochromatographic assay for rapid detection of 1-Aminohydantoin in urine specimens.
A rapid immunochromatographic assay was developed and validated for detection of 1-aminohydantoin (AHD) in urine specimens. Colloidal gold-labeled polyclonal antibody specific to AHD derivative was used as the marker; based on the competitive reactivity theory, the metabolite of nitrofurantoin after derivatization with benzaldehyde would compete with carboxyphenyl AHD derivative-conjugated ovalbumin. The test strip could efficaciously detect the novel analyte with a visual detection limit of 10 ng mL(-1) and high specificity. The reliability of the assay was determined by testing 80 standard samples comparing with enzyme-linked immunosorbent assay. The semi-quantitative detection was accomplished in less than 15 min with low cost, especially for requirements of rapid and simple screening. This is the first publication of an immunochromatographic assay for detection of nitrofuran residues.


71-Mbit/s ultraviolet-B LED communication link based on 8-QAM-OFDM modulation.
A demonstration of ultraviolet-B (UVB) communication link is implemented utilizing quadrature amplitude modulation (QAM) orthogonal frequency-division multiplexing (OFDM). The demonstration is based on a 294-nm UVB-light-emitting-diode (UVB-LED) with a full-width at half-maximum (FWHM) of 9 nm and light output power of 190 μW, at 7 V, with a special silica gel lens on top of it. A -3-dB bandwidth of 29 MHz was measured and a high-speed near-solar-blind communication link with a data rate of 71 Mbit/s was achieved using 8-QAM-OFDM at perfect alignment. 23.6 Mbit/s using 2-QAM-OFDM when the angle subtended by the pointing directions of the UVB-LED and photodetector (PD) is 12 degrees, thus establishing a diffuse-line-of-sight (LOS) link. The measured bit-error rate (BER) of 2.8 ×10-4 and 2.4 ×10-4, respectively, are well below the forward error correction (FEC) criterion of 3.8 ×10-3. The demonstrated high data-rate OFDM-based UVB communication link paves the way for realizing high-speed non-line-of-sight free-space optical communications.


Developing a Lung Model in the Age of COVID-19: A Digital Image Correlation and Inverse Finite Element Analysis Framework.
Pulmonary diseases, driven by pollution, industrial farming, vaping, and the infamous COVID-19 pandemic, lead morbidity and mortality rates worldwide. Computational biomechanical models can enhance predictive capabilities to understand fundamental lung physiology; however, such investigations are hindered by the lung's complex and hierarchical structure, and the lack of mechanical experiments linking the load-bearing organ-level response to local behaviors. In this study we address these impedances by introducing a novel reduced-order surface model of the lung, combining the response of the intricate bronchial network, parenchymal tissue, and visceral pleura. The inverse finite element analysis (IFEA) framework is developed using 3-D digital image correlation (DIC) from experimentally measured non-contact strains and displacements from an ex-vivo porcine lung specimen for the first time. A custom-designed inflation device is employed to uniquely correlate the multiscale classical pressure-volume bulk breathing measures to local-level deformation topologies and principal expansion directions. Optimal material parameters are found by minimizing the error between experimental and simulation-based lung surface displacement values, using both classes of gradient-based and gradient-free optimization algorithms and by developing an adjoint formulation for efficiency. The heterogeneous and anisotropic characteristics of pulmonary breathing are represented using various hyperelastic continuum formulations to divulge compound material parameters and evaluate the best performing model. While accounting for tissue anisotropy with fibers assumed along medial-lateral direction did not benefit model calibration, allowing for regional material heterogeneity enabled accurate reconstruction of lung deformations when compared to the homogeneous model. The proof-of-concept framework established here can be readily applied to investigate the impact of assorted organ-level ventilation strategies on local pulmonary force and strain distributions, and to further explore how diseased states may alter the load-bearing material behavior of the lung. In the age of a respiratory pandemic, advancing our understanding of lung biomechanics is more pressing than ever before.


Effects of supplemental zinc sulfate on growth performance, carcass characteristics, and antimicrobial resistance in feedlot heifers.
Effects of supplemental Zn as Zn sulfate on feedlot performance, carcass traits, and antimicrobial resistance were evaluated using 480 crossbred heifers (BW = 385 kg ± 13.08) in a randomized complete block design. Heifers were blocked by BW and randomly assigned within block to diets with 0, 30, 60, or 90 mg supplemental Zn/kg DM. Heifers were housed in dirt-surfaced pens (20 animals per pen; 6 pens per treatment) equipped with fence-line feed bunks and automatic water fountains. Heifers were fed once daily to ensure ad libitum intake. Plasma was collected on day 0 from five randomly selected heifers per pen and repeated on days 63 and 115 to determine plasma Zn concentrations. Random samples of freshly voided feces were collected from the surface of each pen the day of harvest to determine antibiotic resistance. Heifers were transported on day 144 to a commercial abattoir where hot carcass weight (HCW) and incidence of liver abscesses were recorded at harvest and HCW, dressed yield, ribeye area, 12th rib fat, quality and yield grades were recorded after 36 h of refrigeration. Plasma Zn concentration increased (P = 0.02) linearly in response to increasing concentrations of dietary Zn. Final BW and ADG were unaffected by supplementation (P ≥ 0.29). Quantified levels of resistance to ceftriaxone and tetracycline among fecal Escherichia coli were not impacted (P > 0.05) by dietary zinc concentrations. Increasing Zn concentrations tended to decrease (linear effect, P = 0.07) DMI, resulting in a linear (P = 0.03) and tendency for quadratic (P = 0.12) improvement in feed efficiency with increasing Zn concentration. No differences were detected for HCW, dressed yield, ribeye area, 12th rib fat, percentages of carcasses grading Select or Choice, or yield grade (P > 0.53), but added Zn tended to affect percentage of carcasses that graded Prime, peaking at 60 mg/kg added Zn (quadratic effect, P = 0.07). In vitro fermentations were performed using ruminal fluid cultures containing 0, 30, 60, 90, 120, or 150 mg Zn/kg substrate DM to determine impact of Zn on gas production, VFA concentrations, and in vitro DM disappearance (IVDMD). There were no effects of Zn on in vitro gas production, IVDMD, or most VFA (P > 0.15), but isovalerate decreased linearly in response to added Zn (P = 0.05). Supplementing finishing heifers up to 60 mg Zn/kg diet DM improved feed efficiency compared to other treatments.


Asymptomatic neonatal contamination with herpes simplex virus.
Frequent maternal vaginal and/or lesion cultures for herpes simplex virus (HSV) were obtained from a high-risk maternal population during the course of pregnancy and from oropharyngeal samples of their newborn infants on the first day of life to determine (1) the incidence of asymptomatic neonatal contamination with HSV and (2) the relationship of neonatal with maternal colonization. Four hundred ninety-nine maternal cultures were obtained from 85 patients. The mean number of cultures per patient was six with a range from one to 12. Thirty-three mothers had 41 positive cultures. Fifty-two women had 301 negative cultures. Cord blood HSV-enzyme-linked immunosorbent assay (ELISA) titers were not different in the two groups of infants (geometric mean titer 1152 and 800, respectively). One infant from each maternal group had a positive oropharyngeal HSV culture. Both infants were asymptomatic. One was delivered by elective cesarean section at term to a mother with four positive cultures obtained during pregnancy. Fetal membranes were intact until delivery. The second infant with a positive oropharyngeal culture on the first day of life was born vaginally to a mother with seven negative cultures during pregnancy. Repeat cultures on both infants during the first week of life were negative. These data indicate that asymptomatic neonatal contamination with HSV does occur in oropharyngeal samples obtained on the first day of life. The data also suggest that there is a poor relationship of viral excretion during pregnancy or the mode of delivery with neonatal contamination. Further data are required to determine the incidence of asymptomatic neonatal contamination and the relationship of maternal with neonatal cultures.(ABSTRACT TRUNCATED AT 250 WORDS)


The pulmonary artery catheter: is it still alive?
The present review discusses the current role of the pulmonary artery catheter (PAC) in the hemodynamic monitoring of critically ill patients. The PAC has an important role in the characterization and management of hemodynamic alterations in critically ill patients. Use of the PAC has decreased in the last 30 years because of recent advances in less invasive hemodynamic monitoring techniques, in particular transpulmonary thermodilution and echocardiography, combined with the publication of the results of several randomized trials that failed to show improvements in outcome with the use of the PAC in various settings. Although it is obvious that the PAC should not be used in most critically ill patients, the PAC is still indicated in some patients with circulatory and/or respiratory failure, especially when associated with pulmonary hypertension or left heart dysfunction. As for any technique, optimal PAC use requires expertise in insertion, acquisition, and interpretation of measurements. The decrease in use of the PAC may unfortunately limit exposure of junior doctors and nurses to this device, so that they become less familiar with using the PAC, making it more complicated and less optimal. The PAC still has an important role in the cardiopulmonary monitoring of critically ill patients.


The risk elicitation puzzle.
Evidence shows that people's preference for risk changes considerably when measured using different methods, which led us to question whether the common practice of using a single behavioural elicitation method (EM) reflects a valid measure. The present study addresses this question by examining the across-methods consistency of observed risk preferences in 1,507 healthy participants using six EMs. Our analyses show that risk preferences are not consistent across methods when operationalized on an absolute scale, a rank scale or the level of model parameters of cumulative prospect theory. This is at least partly explained by the finding that participants do not consistently follow the same decision strategy across EMs. After controlling for methodological and human factors that may impede consistency, our results challenge the view that different EMs manage to stably capture risk preference. Instead, we interpret the results as suggesting that risk preferences may be constructed when they are elicited, and different cognitive processes can lead to varying preferences.


[Methodical aspects of using furylacryloylphenylalanylglycineglycine for photometric determination of the activity of angiotensin-converting enzyme].
Different aspects of photometric assay of angiotensin converting enzyme (ACE) with synthetic cromogenic substrate N-(3-[2-furyl]-acryloyl)-phe-gly-gly (FAPGG) were evaluated. At FAPGG concentration exceeding 0.025 mM the absorbance does not follow Burger-Lambert-Bar dependences. Under three conditions the rate of absorbance of the reaction medium strongly depends on properties of spectral weight band. This explains dramatic interamlyser variations and complicetes standardization of the method. Linear dependence between photometic response and ACE activity. The employment of special inhibitor be recommended for elimination of interference.


Combined ECT and Lithium Therapy.
Current guidelines for clinical practice advise against the concurrent use of lithium during a course of electroconvulsive therapy (ECT) owing to an increased risk of morbidity involving the central nervous system. A reappraisal of the evidence indicates that the hazards of this combination treatment may have been overestimated. Although the potential therapeutic advantages of the combination treatment over ECT or lithium alone remain to be clarified, in special clinical situations, and with proper precautions, ECT-lithium combination may be used safely and effectively as an alternative treatment strategy where conventional therapeutic approaches have failed.


PECAM-1: conflicts of interest in inflammation.
Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) is a cell adhesion and signaling receptor that is expressed on hematopoietic and endothelial cells. PECAM-1 is vital to the regulation of inflammatory responses, as it has been shown to serve a variety of pro-inflammatory and anti-inflammatory functions. Pro-inflammatory functions of PECAM-1 include the facilitation of leukocyte transendothelial migration and the transduction of mechanical signals in endothelial cells emanating from fluid shear stress. Anti-inflammatory functions include the dampening of leukocyte activation, suppression of pro-inflammatory cytokine production, and the maintenance of vascular barrier integrity. Although PECAM-1 has been well-characterized and studied, the mechanisms through which PECAM-1 regulates these seemingly opposing functions, and how they influence each other, are still not completely understood. The purpose of this review, therefore, is to provide an overview of the pro- and anti-inflammatory functions of PECAM-1 with special attention paid to mechanistic insights that have thus far been revealed in the literature in hopes of gaining a clearer picture of how these opposing functions might be integrated in a temporal and spatial manner on the whole organism level. A better understanding of how inflammatory responses are regulated should enable the development of new therapeutics that can be used in the treatment of acute and chronic inflammatory disorders.


Bolsa Família Program and deaths from oral cancer in Brazil: an ecological study.
To assess the effect of coverage of the Bolsa Família Program (BFP) on oral cancer mortality rates in Brazil between 2005 and 2017, adjusting for health care coverage and socioeconomic characteristics of the Brazilian federative units. This is an ecological study using annual data (2005-2017) from all the Brazilian federative units. The dependent variable for this study was the oral cancer mortality rate, standardized by gender and age using the direct standardization technique. BFP coverage was the main independent variable, calculated as the ratio of the number of BFP beneficiaries to those families that should potentially be entitled to this conditional cash transfer. Socioeconomic background and health care coverage were covariables. Choropleth maps were drawn, and space-time cube analysis was used to assess changes in the spatiotemporal distribution of BFP and oral cancer mortality rates. Mixed-effects linear regression analysis estimated the coefficients (β) and 95% confidence intervals (CI) for the association between BFP coverage and oral cancer mortality rates. BFP coverage trends increased and oral cancer mortality rate trends stabilized in Brazilian federative units, except for Maranhão, Goiás, and Minas Gerais, where the oral cancer mortality rates have increased. In the adjusted model, greater BFP coverage was associated with lower oral cancer mortality rates (β -2.10; 95% CI [-3.291, -0.919]). Egalitarian strategies such as BFP can reduce the oral cancer mortality rate. We recommend the follow-up of families benefiting from conditional cash transfer program by oral health teams to reduce the oral cancer mortality rate.


[A retained foreign body in the peritoneal cavity causing intestinal obstruction by intraluminal migration].
Forgetting a foreign body in the abdominal cavity is an unpleasant and avoidable situation. It usually occurs when the preventive protocols are not followed precisely. In such a case clinical consequences are unpredictable and relaparotomy may become necessary. We present the case of a temporary intestinal obstruction six months after a transabdominal hysterectomy. Diagnostic workup revealed a laparotomy-gauze left in the abdominal cavity at the previous operation. Exploration showed that the gauze was actually located in the intestinal lumen. The inflammatory reaction elicited by the foreign body eroded the intestinal wall and allowed its intraluminal migration. The gauze moved distally due to peristalsis until it became trapped in the ileocecal valve causing obstruction. When it finally passed through the valve the obstruction was relieved. Intraoperative maneuvers advanced the foreign body further forward until it was removed transanally. The formal processes - counting the gauzes continually and double crossing the counting - must be kept in every laparotomy to avoid the unpleasant experience of gauze remaining in the peritoneal cavity. In such an unfortunate case traditional open surgery provides a safe solution to the patient's problem.


Accurate Tracking of the Mutational Landscape of Diploid Hybrid Genomes.
Mutations, recombinations, and genome duplications may promote genetic diversity and trigger evolutionary processes. However, quantifying these events in diploid hybrid genomes is challenging. Here, we present an integrated experimental and computational workflow to accurately track the mutational landscape of yeast diploid hybrids (MuLoYDH) in terms of single-nucleotide variants, small insertions/deletions, copy-number variants, aneuploidies, and loss-of-heterozygosity. Pairs of haploid Saccharomyces parents were combined to generate ancestor hybrids with phased genomes and varying levels of heterozygosity. These diploids were evolved under different laboratory protocols, in particular mutation accumulation experiments. Variant simulations enabled the efficient integration of competitive and standard mapping of short reads, depending on local levels of heterozygosity. Experimental validations proved the high accuracy and resolution of our computational approach. Finally, applying MuLoYDH to four different diploids revealed striking genetic background effects. Homozygous Saccharomyces cerevisiae showed a ∼4-fold higher mutation rate compared with its closely related species S. paradoxus. Intraspecies hybrids unveiled that a substantial fraction of the genome (∼250 bp per generation) was shaped by loss-of-heterozygosity, a process strongly inhibited in interspecies hybrids by high levels of sequence divergence between homologous chromosomes. In contrast, interspecies hybrids exhibited higher single-nucleotide mutation rates compared with intraspecies hybrids. MuLoYDH provided an unprecedented quantitative insight into the evolutionary processes that mold diploid yeast genomes and can be generalized to other genetic systems.


Effects of interferon-alpha on cytochrome P-450 isoforms 1A2 and 3A activities in patients with chronic hepatitis C.
The risk of adverse drug interactions with interferon-alpha has been poorly assessed. The aim of our study was to establish whether administration of interferon-alpha at therapeutic doses in patients with chronic hepatitis C may have significant inhibitory effects on other drug metabolism. The study was focused on cytochromes P-450 1A2 and 3A, two major isoforms involved in the metabolism of numerous substrates. Eighteen patients with chronic active hepatitis C requiring an interferon-alpha treatment were studied. Cytochrome P-450 1A2 activity was determined on the basis of an in vivo caffeine metabolism study. Cytochrome P-450 3A activity was determined according to in vivo cortisol metabolism into 6-beta-hydroxycortisol. Both activities were determined 1 month before, at initiation and 1 month after interferon-alpha therapy (3 x 10(6) units, three times a week). There were no significant differences in the caffeine index (CYP 1A2) and in the 6-beta-hydroxycortisol/free cortisol urinary ratio (CYP 3A) before and after alpha interferon treatment Chronic administration of interferon-alpha at therapeutic doses does not change in vivo cytochrome P-450 1A2 and 3A activities. These results support the suggestion that drugs metabolized by these isoenzymes may be used together with interferon-alpha in patients with chronic hepatitis C without significant risks of drug interactions.


Agglutination of isolated rod outer segments by lectins.
The interactions of ten lectins with rod outer segment (ROS) plasma membranes and the effects of various haptene sugars were examined by studying agglutination in suspensions of washed ROSs. It is concluded that agglutination sites on the ROS membrane involve receptors that are recognized by eight lectins with haptene sugar preferences that include D-Gal, D-GalNAc, D-Man, and D-GlcNAc. Lectins binding alpha-L-fucose do not induce agglutination. The identification of some receptors and the significance of these results in terms of the known complexities of lectin specificities is discussed.


Advances in Genetic Engineering Technology and Its Application in the Industrial Fungus Aspergillus oryzae.
The filamentous fungus Aspergillus oryzae is an important strain in the traditional fermentation and food processing industries and is often used in the production of soy sauce, soybean paste, and liquor-making. In addition, A. oryzae has a strong capacity to secrete large amounts of hydrolytic enzymes; therefore, it has also been used in the enzyme industry as a cell factory for the production of numerous native and heterologous enzymes. However, the production and secretion of foreign proteins by A. oryzae are often limited by numerous bottlenecks that occur during transcription, translation, protein folding, translocation, degradation, transport, secretion, etc. The existence of these problems makes it difficult to achieve the desired target in the production of foreign proteins by A. oryzae. In recent years, with the decipherment of the whole genome sequence, basic research and genetic engineering technologies related to the production and utilization of A. oryzae have been well developed, such as the improvement of homologous recombination efficiency, application of selectable marker genes, development of large chromosome deletion technology, utilization of hyphal fusion techniques, and application of CRISPR/Cas9 genome editing systems. The development and establishment of these genetic engineering technologies provided a great deal of technical support for the industrial production and application of A. oryzae. This paper reviews the advances in basic research and genetic engineering technologies of the fermentation strain A. oryzae mentioned above to open up more effective ways and research space for the breeding of A. oryzae production strains in the future.


Molecular analysis of evolutionary changes in the expression of Drosophila esterases.
Drosophila melanogaster transformed with the esterase 5 (Est-5) gene from Drosophila pseudoobscura were used to assess the evolutionary basis for differences in the sex- and tissue-specific expression of the esterase 5 (EST 5) enzyme in D. pseudoobscura relative to its homologue in D. melanogaster, EST 6. EST 5 is expressed in the eyes and hemolymph of transformed D. melanogaster just as it is in D. pseudoobscura, but it is not detectable in the ejaculatory duct, where the homologous enzyme, EST 6, is most abundant. EST 5 also occurs at equal levels in both sexes of the transformants and D. pseudoobscura, whereas EST 6 is more abundant in male than in female D. melanogaster. Northern analysis of transformed and untransformed flies indicates that the expression patterns of EST 5 and EST 6 are controlled at the level of transcription and suggests that regulatory differences between Est-6 and Est-5 have evolved mainly through cis-acting regulatory changes in the two loci rather than through alterations in trans-acting factors. Equal expression of EST 5 in male and female transformants also indicates that the X-chromosome-linked Est-5 gene of D. pseudoobscura, when isolated as a 4.5-kilobase restriction fragment, is not dosage compensated after integration into an autosome of D. melanogaster.


Environmental source of arsenic exposure.
Arsenic is a ubiquitous, naturally occurring metalloid that may be a significant risk factor for cancer after exposure to contaminated drinking water, cigarettes, foods, industry, occupational environment, and air. Among the various routes of arsenic exposure, drinking water is the largest source of arsenic poisoning worldwide. Arsenic exposure from ingested foods usually comes from food crops grown in arsenic-contaminated soil and/or irrigated with arsenic-contaminated water. According to a recent World Health Organization report, arsenic from contaminated water can be quickly and easily absorbed and depending on its metabolic form, may adversely affect human health. Recently, the US Food and Drug Administration regulations for metals found in cosmetics to protect consumers against contaminations deemed deleterious to health; some cosmetics were found to contain a variety of chemicals including heavy metals, which are sometimes used as preservatives. Moreover, developing countries tend to have a growing number of industrial factories that unfortunately, harm the environment, especially in cities where industrial and vehicle emissions, as well as household activities, cause serious air pollution. Air is also an important source of arsenic exposure in areas with industrial activity. The presence of arsenic in airborne particulate matter is considered a risk for certain diseases. Taken together, various potential pathways of arsenic exposure seem to affect humans adversely, and future efforts to reduce arsenic exposure caused by environmental factors should be made.


Induced autoprocessing of the cytopathic Makes caterpillars floppy-like effector domain of the Vibrio vulnificus MARTX toxin.
The multifunctional-autoprocessing repeats-in-toxin (MARTX(Vv)) toxin that harbours a varied repertoire of effector domains is the primary virulence factor of Vibrio vulnificus. Although ubiquitously present among Biotype I toxin variants, the 'Makes caterpillars floppy-like' effector domain (MCF(Vv)) is previously unstudied. Using transient expression and protein delivery, MCF(Vv) and MCF(Ah) from the Aeromonas hydrophila MARTX(Ah)) toxin are shown for the first time to induce cell rounding. Alanine mutagenesis across the C-terminal subdomain of MCF(Vv) identified an Arg-Cys-Asp (RCD) tripeptide motif shown to comprise a cysteine protease catalytic site essential for autoprocessing of MCF(Vv). The autoprocessing could be recapitulated in vitro by the addition of host cell lysate to recombinant MCF(Vv), indicating induced autoprocessing by cellular factors. The RCD motif is also essential for cytopathicity, suggesting autoprocessing is essential first to activate the toxin and then to process a cellular target protein resulting in cell rounding. Sequence homology places MCF(Vv) within the C58 cysteine protease family that includes the type III secretion effectors YopT from Yersinia spp. and AvrPphB from Pseudomonas syringae. However, the catalytic site RCD motif is unique compared with other C58 peptidases and is here proposed to represent a new subgroup of autopeptidase found within a number of putative large bacterial toxins.


MicroRNA-138: an emerging regulator of skeletal development, homeostasis, and disease.
Noncoding microRNAs are powerful epigenetic regulators of cellular processes by their ability to target and suppress expression of numerous protein-coding mRNAs. This multitargeting function is a unique and complex feature of microRNAs. It is now well-described that microRNAs play important roles in regulating the development and homeostasis of many cell/tissue types, including those that make up the skeletal system. In this review, we focus on microRNA-138 (miR-138) and its effects on regulating bone and cartilage cell differentiation and function. In addition to its reported role as a tumor suppressor, miR-138 appears to function as an inhibitor of osteoblast differentiation. This review provides additional information on studies that have attempted to alter miR-138 expression in vivo as a means to dampen ectopic calcification or alter bone mass. However, a review of the published literature on miR-138 in cartilage reveals a number of contradictory and inconclusive findings with respect to regulating chondrogenesis and chondrocyte catabolism. This highlights the need for more research in understanding the role of miR-138 in cartilage biology and disease. Interestingly, a number of studies in other systems have reported miR-138-mediated effects in dampening inflammation and pain responses. Future studies will reveal if a multifunctional role of miR-138 involving suppression of ectopic bone, inflammation, and pain will be beneficial in skeletal conditions such as osteoarthritis and heterotopic ossification.


Probiotic treatment reduces appetite and glucose level in the zebrafish model.
The gut microbiota regulates metabolic pathways that modulate the physiological state of hunger or satiety. Nutrients in the gut stimulate the release of several appetite modulators acting at central and peripheral levels to mediate appetite and glucose metabolism. After an eight-day exposure of zebrafish larvae to probiotic Lactobacillus rhamnosus, high-throughput sequence analysis evidenced the ability of the probiotic to modulate the microbial composition of the gastrointestinal tract. These changes were associated with a down-regulation and up-regulation of larval orexigenic and anorexigenic genes, respectively, an up-regulation of genes related to glucose level reduction and concomitantly reduced appetite and body glucose level. BODIPY-FL-pentanoic-acid staining revealed higher short chain fatty acids levels in the intestine of treated larvae. These results underline the capability of the probiotic to modulate the gut microbiota community and provides insight into how the probiotic interacts to regulate a novel gene network involved in glucose metabolism and appetite control, suggesting a possible role for L. rhamnosus in the treatment of impaired glucose tolerance and food intake disorders by gut microbiota manipulation.


[Anesthesia during diagnostic and therapeutic endoscopic abdominal procedures].
The results of a retrospective study of peculiarities of anesthetic management at emergency diagnostic endoscopic interventions in abdominal organs are presented in the article. Anesthesia-related risk factors, peculiarities of surgery duration and most often complications, encountered during operation and immediately after it, were analyzed in cases of the administration of multi-component combined endotracheal narcosis (MCEN), intravenous anesthesia, intramuscular sedation and local anesthesia. It was pointed out that the need to revise the anesthetic tactic (use of another type of anesthetic management) appeared in cases of intravenous anesthesia (27%), intramuscular sedation (20%) or local anesthesia (40%). Complications were encountered, during the early postoperative period in breathing organs, 9-18% (pneumothorax, pneumonia), in case of intravenous anesthesia of diagnostic laparoscopy. PONV syndrome was on the top of complications' list (42%) in MCEN. In order to optimize the medical care rendered to patients, who are admitted to the emergency surgery department, multi-component combined endotracheal narcosis is suggested as a method of choice for diagnostic laparoscopic interventions; a management algorithm and MCEN peculiarities are defined.


[Coronary angioplasty. Results observed in 14 cases].
Between December, 1985, and May, 1988 we have performed coronary angioplasty of 14 lesions in 12 patients. Before angioplasty 8 patients had a history of unstable angina, and 3 developed angina after streptokinase because of an acute myocardial infarction. We attempted angioplasty of 11 proximal and 3 distal lesions; these included a coronary bypass graft lesion, and 3 lesions in one vessel. We successfully dilated 12 lesions (85%). The coronary stenosis was reduced on average from 84.2 +/- 9 to 17.5 +/- 7 per cent (P less than 0.0001); and the pressure gradient was reduced from 74 +/- 16.25 to 18.3 +/- 9 mmHg (P less than 0.001). Procedure-related complications included: coronary occlusion in 4 patients (28.5%) that were successfully resolved during angioplasty in 3 patients, but one developed myocardial infarction (8.3%); and one urgent surgery and death in a patient with 3 vessel disease. Twelve patients (83%) with no evidence of myocardial ischemia returned to their normal activities. These initial data confirm coronary angioplasty as a safe, efficatious and successful alternative in the management of selected patients with coronary artery disease.


Support Vector Machine model for hERG inhibitory activities based on the integrated hERG database using descriptor selection by NSGA-II.
Assessing the hERG liability in the early stages of drug discovery programs is important. The recent increase of hERG-related information in public databases enabled various successful applications of machine learning techniques to predict hERG inhibition. However, most of these researches constructed the datasets from only one database, limiting the predictability and scope of the models. In this study, a hERG classification model was constructed using the largest dataset for hERG inhibition built by integrating multiple databases. The integrated dataset consisted of more than 291,000 structurally diverse compounds derived from ChEMBL, GOSTAR, PubChem, and hERGCentral. The prediction model was built by support vector machine (SVM) with descriptor selection based on Non-dominated Sorting Genetic Algorithm-II (NSGA-II) to optimize the descriptor set for maximum prediction performance with the minimal number of descriptors. The SVM classification model using 72 selected descriptors and ECFP_4 structural fingerprints recorded kappa statistics of 0.733 and accuracy of 0.984 for the test set, substantially outperforming the prediction performance of the current commercial applications for hERG prediction. Finally, the applicability domain of the prediction model was assessed based on the molecular similarity between the training set and test set compounds.


Dimethylheptyl-THC-11 oic acid: a nonpsychoactive antiinflammatory agent with a cannabinoid template structure.
To assess the antiinflammatory activity of dimethylheptyl-THC-11 oic acid (DMH-11C), a nonpsychoactive synthetic derivative of tetrahydrocannabinol. Acute inflammation was induced by injection of interleukin-1beta and tumor necrosis factor alpha into subcutaneous air pouches formed on the backs of mice. Inflammation was quantified 6 hours later by pouch fluid leukocyte counts. Adjuvant-induced polyarthritis in rats was used as a model of chronic inflammation and joint tissue injury. Animals were either untreated, treated with safflower oil, or treated with DMH-11C in safflower oil. Arthritis was assessed by clinical observation and by histomorphologic evaluation of tibiotarsal joints. Oral administration of DMH-11C reduced the accumulation of pouch fluid leukocytes and significantly reduced the severity of adjuvant-induced polyarthritis. Histopathologic studies of tibiotarsal joints showed that DMH-11C treatment attenuated pannus formation and joint tissue injury. DMH-11C suppresses acute inflammation in the subcutaneous air pouch in mice and chronic joint inflammation characteristic of adjuvant disease in rats. These results demonstrate the potential use of this nonpsychoactive cannabinoid as an antiinflammatory agent.


Inhibition of growth and induction of apoptosis by all-trans retinoic acid in lymphoid cell lines transfected with the PML/RAR alpha fusion gene.
The interaction of an exogenous PML/RAR alpha fusion gene associated with acute promyelocytic leukaemia, with all-trans retinoic acid (ATRA) was examined in two lymphoid cell lines. L1210 and MOLT-4 cells were transfected with PML/RAR alpha cDNA in the expression vector pGD and stable transformants (L1210PML/RAR alpha and MOLT-4PML/RAR alpha) were selected with G418. ATRA inhibited the growth of these stable transformants, as assessed by [3H]thymidine incorporation, in a dose-dependent manner, but had no effect on the growth of control cells stably transformed with neomycin resistant gene alone. ATRA also induced apoptosis, as assessed by fragmentation of genomic DNA, in L121OPML/RAR alpha and MOLT-4PML/RAR alpha cells but not in control cells. The exogenous PML/RAR alpha fusion gene therefore probably mediates the effects of ATRA on cell growth and apoptosis in these cell lines.


Self-administered written prompts to teach home accident prevention skills to adults with brain injuries.
This study evaluated the use of written checklists and task analyses as self-administered prompts to teach home accident prevention skills to 4 adults with brain injuries. Subsequent to baseline, participants used written checklists that identified potential in-home hazards but did not prompt behaviors necessary for hazard remediation. Written individualized task analyses, incorporating specific behavioral steps for correcting hazards that participants had failed to remediate during the checklist phase, were used to prompt appropriate responding when necessary. These were subsequently faded to transfer stimulus control to the natural conditions. A multiple probe technique across participants and settings was used. Results indicated that the checklist alone was sufficient to increase appropriate responses to many of the potential hazards. Individualized task analyses, when needed, resulted in appropriate remediation of all potential hazards. Generalization to untrained potential hazards occurred to some degree for all participants. Follow-up results showed that most skills trained were maintained over a 1-month period.


Identification of glycan structure alterations on cell membrane proteins in desoxyepothilone B resistant leukemia cells.
Resistance to tubulin-binding agents used in cancer is often multifactorial and can include changes in drug accumulation and modified expression of tubulin isotypes. Glycans on cell membrane proteins play important roles in many cellular processes such as recognition and apoptosis, and this study investigated whether changes to the glycan structures on cell membrane proteins occur when cells become resistant to drugs. Specifically, we investigated the alteration of glycan structures on the cell membrane proteins of human T-cell acute lymphoblastic leukemia (CEM) cells that were selected for resistance to desoxyepothilone B (CEM/dEpoB). The glycan profile of the cell membrane glycoproteins was obtained by sequential release of N- and O-glycans from cell membrane fraction dotted onto polyvinylidene difluoride membrane with PNGase F and β-elimination respectively. The released glycan alditols were analyzed by liquid chromatography (graphitized carbon)-electrospray ionization tandem MS. The major N-glycan on CEM cell was the core fucosylated α2-6 monosialo-biantennary structure. Resistant CEM/dEpoB cells had a significant decrease of α2-6 linked sialic acid on N-glycans. The lower α2-6 sialylation was caused by a decrease in activity of β-galactoside α2-6 sialyltransferase (ST6Gal), and decreased expression of the mRNA. It is clear that the membrane glycosylation of leukemia cells changes during acquired resistance to dEpoB drugs and that this change occurs globally on all cell membrane glycoproteins. This is the first identification of a specific glycan modification on the surface of drug resistant cells and the mechanism of this downstream effect on microtubule targeting drugs may offer a route to new interventions to overcome drug resistance.


Multifaceted roles of adiponectin in cancer.
Obesity is linked to increased cancer risk. Pathological expansion of adipose tissue impacts adipocyte function and secretion of hormonal factors regulating tissue homeostasis and metabolism. Adiponectin is an adipocyte-secreted, circulating hormone with pleiotropic functions in lipid and glucose metabolism, and beneficial roles in cardiovascular functions and inflammation. In obesity, decreased Adiponectin plasma levels correlate with tumor development and progression. The association of Adiponectin with potential tumor-limiting functions has raised significant interest in exploring this adipokine as a target for cancer-diagnostic and therapeutic applications. Recent studies, however, also implicate Adiponectin in supporting malignancy. This review highlights the evidence that links Adiponectin signaling to either cancer-protective or cancer-supporting functions. In this context, we discuss Adiponectin interactions with its receptors and associated signaling pathways. Despite significant advances in understanding Adiponectin functions and signaling mechanisms, its role in cancer remains multifaceted and subject to controversy.


Antibiotic-resistant flora in nursing home patients admitted to the hospital.
To study carriage of multiply resistant gram-negative bacilli, 50 patients admitted to the hospital from nursing homes (NHs) and 50 control admissions not from NHs were matched for age and recent antibiotic use. Their antibiotic resistance patterns were similar: 20 NH patients and 14 controls had resistant strains. However, significantly more patients (64%) from NHs with large numbers of "skilled beds" had resistant bacteria than did patients from small NHs (21%) or controls (28%). Also, more patients from NHs had members of the Proteus-Providencia-Morganella group in their urine than did controls. Discriminant analysis showed that residence in NHs with large numbers of skilled beds, recent antibiotic use, and bladder dysfunction (indwelling catheter or incontinence) were independently important in predicting carriage of resistant strains in NH and control patients. Over 75% of resistant isolates were from rectal specimens, emphasizing the occult way that such strains are brought into the hospital.


Apocrine gland adenocarcinoma and pheochromocytoma in a cat.
A 15-year-old, castrated male domestic shorthair was presented for a recurrent, perineal apocrine gland adenocarcinoma. A right adrenal mass was identified on abdominal radiography and ultrasonography performed as routine staging prior to surgical excision of the perineal tumor. An ultrasonographic-guided biopsy of the adrenal mass was performed and a pheochromocytoma was diagnosed upon histopathology. The perineal and adrenal tumors were removed surgically. The cat developed fatal thromboembolic disease following surgery and was euthanized. This is the third reported case of phenochromocytoma in a cat and is unusual in that two rare tumors were identified in one animal.


The correlation of Salvia miltiorrhiza extract-induced regulation of osteoclastogenesis with the amount of components tanshinone I, tanshinone IIA, cryptotanshinone, and dihydrotanshinone.
Tanshinone I, tanshinone IIA, cryptotanshinone, and dihydrotanshinone are compounds that have been isolated from the root of Salvia miltiorrhiza (SM), which is also known as "Danshen." The SM extract has been used successfully in China for treating postmenopausal syndrome. Furthermore, it was previously reported that SM had inhibitory effect on osteoporosis in ovariectomized rats. Another study reported that the four components, tanshinone I, tanshinone IIA, cryptotanshinone, and dihydrotanshinone, prevented osteoclast function in an in vitro system. However, there are no reports of a correlation between SM and its components on osteoporosis and osteoclast function. This study was undertaken to examine the effect of SM on osteoclastogenesis and osteoblast differentiation, which are two important markers of the bone physiology. Through a rapid, sensitive and specific isocratic liquid chromatography/tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantitative determination of four diterpenoids, tanshinone I, tanshinone IIA, cryptotanshinone, and dihydrotanshinone in SM, the authors tried to correlate the amount of tanshinone compounds in SM into the antiosteoclast activity. The SM fraction (methanol and ethanol isolated) with a low concentration of tanshinone IIA (1 mug/mL) had no effect on the alkaline phosphotase activity (osteoblast differentiation), but completely inhibited osteoclastogenesis. Although the tanshinone compound itself showed similar effects, the concentrations of commercially available tanshinone (diterpenoids, tanshinone I, tanshinone IIA, cryptotanshinone, and dihydrotanshinone) needed for antiosteoclast activity was almost 1000 times more than that of tanshinone in SM fraction. This suggests that there are other unknown compounds in the SM extract that have a synergistic effect with tanshinone. These results also suggest that tanshinone can be a good marker compound to explain the antiosteoporotic function of SM.


Production and Assessment of Poly(Lactic Acid) Matrix Composites Reinforced with Regenerated Cellulose Fibres for Fused Deposition Modelling.
Additive manufacturing can be a valuable tool to process polymeric composites reinforced with bio-based fibres, extending their use and opening new opportunities for more environmentally friendly materials. In this work, poly(lactic acid) (PLA) composites reinforced with regenerated cellulose fibres (lyocell) were processed into novel filaments and used for 3D printing. The Young's modulus of the filaments increased with the addition of fibres, but substantial porosity was observed in formulations with 20 and 30 wt% of fibre content. Nonetheless, the composites were easily printed, and the formulation with 10 wt% of fibres presented the best tensile properties of 3D printed samples with average tensile strength, Young's modulus, and strain at break of 64.2 MPa, 4.56 GPa, and 4.93%, respectively. It has been shown in this study that the printing process contributes to fibre alignment with small variations depending on the printing speed. Printed composite samples also had superior thermo-mechanical stability with a storage modulus up to 72 times higher than for neat PLA at 80 °C after the composite samples were heat-treated. In general, this work supports the potential use of regenerated cellulose fibres to reinforce PLA for 3D printing applications.


Extracorporeal photochemotherapy in the treatment of cutaneous T-cell lymphoma. Complexity of objective evaluation.
The term cutaneous T-cell lymphoma (CTCL) encompasses the spectrum of diseases characterized by a monoclonal proliferation of malignant T lymphocytes predominantly of the mature T-helper cell type. These include mycosis fungoides, which is usually localized to the skin for many years, and the Sezary syndrome, the leukemic variant in which characteristic, bizarre lymphatic cells with deeply indented or cerebriform nuclei, the Sezary cells, infiltrate lymph glands and internal organs such as the spleen, liver, lungs, heart, and bone marrow. The condition is more common in men after their fourth decade. The treatment of CTCL varies depending on the stage of the disease. The skin of the patient is the primary index of effectiveness of therapy. Options range from topical steroids, topical nitrogen mustard, X-irradiation, electron beam irradiation, and 8-methoxypsoralen (8-MOP) combined with ultraviolet A photochemotherapy (PUVA), to leukapheresis and systemic chemotherapy. More recently, extracorporeal photochemotherapy (ECPC) has been introduced. The safety and efficacy of this modality is further investigated in six patients who fulfilled the criteria of diagnosis of CTCL. The problems encountered in objectively evaluating the clinical responses in the patients are outlined and improvements in the protocol to overcome these are suggested. The proposed mechanism of action is an immunostimulatory one and a procedure that is relatively free from side effects; it offers promise as a potential treatment for a difficult cancer.


Prenatal cannabinoid exposure: why expecting individuals should take a pregnancy pause from using cannabinoid products.
Cannabinoid use in all populations is increasing as legalization across the United States continues. Concerningly, there is a lack of caution provided by medical providers to pregnant individuals as to the impact the use of cannabinoids could have on the developing fetus. Research continues in both the preclinical and clinical areas, and is severely needed, as the potency of delta-9-tetrahydrocannabinol (THC), the primary psychoactive component of cannabis, has increased dramatically since the initial studies were completed. Thus far, clinical studies raise compelling evidence for short term memory deficits, impulse control issues, and attention deficiencies following prenatal cannabinoid exposure (PCE). These changes may be mediated through epigenetic modifications that not only impact the current offspring but could carry forward to future generations. While additional studies are needed, a pregnancy pause from cannabinoid products should be strongly recommended by providers to ensure the optimal health and well-being of our future generations.


The efficacy of intrauterine infusion of platelet rich plasma in women undergoing assisted reproduction: a systematic review and meta-analysis.
Platelet-rich plasma (PRP) is an autologous platelet concentration recently used in the reproductive field. Studies had conflicting results regarding its effect on pregnancy outcomes. We aimed to solve the debate on the safety and efficacy of PRP in women undergoing assisted reproduction and assess the influence of covariates on the outcomes of PRP infusion. We searched PubMed, Scopus, Cochrane, and Web of Science in May 2023. We included randomized and non-randomized clinical trials as well as cohort studies assessing intrauterine PRP in sub fertile women undergoing assisted reproduction (IVF/ICSI). For the quality assessment, We used the Cochrane Risk of Bias Tool 1, the ROBINS-I tool, and the Newcastle-Ottawa Scale. We pooled the data using RevMan version 5.4. The data from 23 studies were pooled. PRP had favorable outcomes compared with the control group on clinical pregnancy rate (RR: 1.84, 95% CI 1.62 to 2.09; P < 0.00001), live birth rate (RR: 1.75, 95% CI: 1.24 to 2.47; P = 0.001), and miscarriages (RR: 0.51, 95% CI: 0.36 to 0.72; P = 0.0002). Women with repeated implantation failure had a significantly improved clinical pregnancy rate (RR: 1.83, 95% CI: 1.49 to 2.24; P < 0.00001), live birth rate (RR:1.83, 95% CI: 1.33 to 2.51; P = 0.002), and miscarriage rate (RR: 0.46, 95% CI: 0.31 to 068; P = 0.0001). PRP showed promising results in assisted reproductive techniques. Further large and multicenter RCTs are required to compare the doses of PRP while identifying the specific population with the most benefits from PRP.


Human Breast Cancer Stem Cells Have Significantly Higher Rate of Clathrin-Independent and Caveolin-Independent Endocytosis than the Differentiated Breast Cancer Cells.
Breast Cancer Stem (BCS) cells play critical roles in self-renewal, Multi Drug Resistance (MDR), differentiation and generation of secondary tumors. Conventional chemotherapy may efficiently kill the bulk of differentiated drug sensitive breast cancer cells, but not the MDR self-renewable BCS cells, leading to enrichment of the MDR BCS cells. In order to target the MDR BCS cells, we have isolated: 1) BCS cells from either breast cancer cell lines or fresh breast cancer specimens; 2) ATP binding cassette (ABC) transporter group G number 2 (ABCG2)-specific aptamers; and 3) BCS cell-binding aptamers. Interestingly, ABCG2-specific aptamers labeled the membrane surface of the ABCG2-expressing baby hamster kidney (BHK) cells, but stained whole cells of the BCS cells derived from mammospheres, implying that BCS cells might have much higher rate of endocytosis than the ABCG2-expressing BHK cells. In addition, 5D3, a monoclonal antibody that recognizes the extracellular loops of ABCG2 protein, also stained whole BCS cells. Furthermore, BCS cell-binding aptamers stained whole BCS cells, but not the differentiated breast cancer MCF-7 cells. All these results support above conclusion that BCS cells might have high rate of endocytosis. Further experiments performed with aptamers and human transferrin or lactosylceramide showed that BCS cells do have much higher endocytosis rate than the differentiated breast cancer cells. Interestingly, clathrin dependent endocytosis inhibitors, such as monodansylcadaverine or sucrose, or caveolin-dependent endocytosis inhibitors, such as methyl-β-cyclodextrin or genistein, can inhibit the internalization of transferrin or lactosylceramide into the differentiated breast cancer cells, but cannot block the internalization of these compounds into the BCS cells, suggesting that BCS cells undergo clathrin-independent and caveolin-independent endocytosis. Taken together, our data suggest that BCS cells have high rate of endocytosis and open the possibilities for delivering therapeutic agents directly into the MDR BCS cells with aptamer-coated liposomes.


Maplexins, new α-glucosidase inhibitors from red maple (Acer rubrum) stems.
Thirteen gallic acid derivatives including five new gallotannins, named maplexins A-E, were isolated from red maple (Acer rubrum) stems. The compounds were identified by spectral analyses. The maplexins varied in number and location of galloyl groups attached to 1,5-anhydro-d-glucitol. The isolates were evaluated for α-glucosidase inhibitory and antioxidant activities. Maplexin E, the first compound identified with three galloyl groups linked to three different positions of 1,5-anhydro-d-glucitol, was 20 fold more potent than the α-glucosidase inhibitory drug, Acarbose (IC(50)=8 vs 160 μM). Structure-activity related studies suggested that both number and position of galloyls attached to 1,5-anhydro-d-glucitol were important for α-glucosidase inhibition.


Update on the use of streptomycin therapy for Meniere's disease.
An update of our experiences in the treatment of Meniere's disease with intramuscular streptomycin sulfate reveals great success in relief of episodic vertigo. Hearing losses that existed before the treatment are generally stabilized and occasionally improved. Because of the considerable morbidity caused by arduous therapy, prolonged ataxia, and occasional oscillopsia, we recommend that the treatment be reserved for the bilateral disabling form of the disease.


Molecular biology of sodium channels and their role in cardiac arrhythmias.
The sodium channel is an integral membrane protein that plays a central role in conduction of the cardiac impulse in working cardiac myocytes and cells of the His-Purkinje system. The channel has two fundamental properties, ion conduction and gating. Specific domains of the channel protein control each of these functions. Ion conduction describes the mechanisms of the selective movement of sodium ion across the pore in the cell membrane. The selectivity of the channel for sodium ions is at least 10 times greater than that for other monovalent cations; the channel does not normally conduct divalent cations. Gating describes the opening and closing of the sodium channel pore. Sodium channels open transiently during membrane depolarization and close by a process termed inactivation. The cardiac sodium channel protein is a multimeric complex consisting of an alpha and an auxiliary beta-subunit. The genes encoding the sodium channel have been cloned and sequenced. The alpha subunit gene, SCN5A is sufficient to express a functional channel. However, beta subunit co-expression increases the level of channel expression and alters the voltage dependence of inactivation. Mutations of the sodium channel may result in incomplete inactivation during maintained depolarization, a decrease in the level of channel expression or acceleration of inactivation. The resulting clinical phenotypes include long QT syndrome, type III (LQT III), Brugada syndrome, and heart block. LQT III and Brugada syndromes have a high case fatality rate and are best treated with an implantable defibrillator.


Recent advances of polymeric nanoplatforms for cancer treatment: smart delivery systems (SDS), nanotheranostics and multidrug resistance (MDR) inhibition.
Nanotheranostics is a promising field that combines the benefits of diagnostic and treatment into a single nano-platform that not only administers treatment but also allows for real-time monitoring of therapeutic response, decreasing the possibility of under/over-drug dosing. Furthermore, developing smart delivery systems (SDSs) for cancer theranostics that can take advantage of various tumour microenvironment (TME) conditions (such as deformed tumour vasculature, various over-expressed receptor proteins, reduced pH, oxidative stress, and resulting elevated glutathione levels) can aid in achieving improved pharmacokinetics, higher tumour accumulation, enhanced antitumour efficacy, and/or decreased side effects and multidrug resistance (MDR) inhibition. Polymeric nanoparticles (PNPs) are being widely investigated in this regard due to their unique features such as small size, passive/active targeting possibility, better pharmaceutical kinetics and biological distribution, decreased adverse reactions of the established drugs, inherent inhibitory properties to MDR efflux pump proteins, as well as the feasibility of delivering numerous therapeutic substances in just one design. Hence in this review, we have primarily discussed PNPs based targeted and/or controlled SDSs in which we have elaborated upon different TME mediated nanotheranostic platforms (NTPs) including active/passive/magnetic targeting platforms along with pH/ROS/redox-responsive platforms. Besides, we have elucidated different imaging guided cancer therapeutic platforms based on four major cancer imaging techniques i.e., fluorescence/photo-acoustic/radionuclide/magnetic resonance imaging, Furthermore, we have deliberated some of the most recently developed PNPs based multimodal NTPs (by combining two or more imaging or therapy techniques on a single nanoplatform) in cancer theranostics. Moreover, we have provided a brief update on PNPs based NTP which are recently developed to overcome MDR for effective cancer treatment. Additionally, we have briefly discussed about the tissue biodistribution/tumour targeting efficiency of these nanoplatforms along with recent preclinical/clinical studies. Finally, we have elaborated on various limitations associated with PNPs based nanoplatforms.


The influence of DC voltage on the conductivity of chloroprene rubber-carbon black composites for flexible resistive heating elements.
In order to acquire a flexible resistive heating element in the temperature range for human body heating, the influence of DC voltage on chloroprene rubber (CR) and carbon black (CB) composites has been investigated. Three conduction mechanisms have been found to occur in the range from 0.5 V to 10 V - charge velocity increase due to the increase of the electric field, matrix thermal expansion that results in decreased tunnelling currents and new electroconductive channel formation at voltages above 7.5 V, where the temperature exceeds the matrix's softening point. As opposed to external heating, during resistive heating, the composite exhibits a negative temperature coefficient of resistivity up to an applied voltage of 5 V. The intrinsic electro-chemical matrix properties play an important role in the overall resistivity of the composite. The material shows cyclical stability when repeatedly applying a voltage of 5 V and can be used as a human body heating element.


Massive hiatus hernia mimicking a left atrial mass.
Echocardiography is the investigational tool of choice for identifying cardiac masses. However, extracardiac masses may lead to a misdiagnosis. We present a unique case of a massive hiatus hernia in a 93 year-old woman, compressing on the left atrium, mimicking a left atrial mass. Echocardiographic features suggestive of a hiatus hernia are discussed.


Barriers to health care access among refugee asylum seekers.
Asylum seekers have poor access to health care. Qualitative data portraying their experience is lacking. We conducted focus groups and comprehensive interviews with 35 asylum seekers and 15 expert providers/advocacy organization representatives. Purposive sampling was used to recruit subgroups. Interviews were recorded, coded, and analyzed. 85% male, mostly from African countries. Major barriers: a) Internal, including mental illness, fatalism, mistrust, and perceived discrimination; b) Structural, including affordability, limited services, inadequate interpretation, resettlement challenges such as shelter, food, and employment insecurity; health care for urgent care only; and poor cultural competency; c) Barriers in social assimilation, including difficulty navigating a complex system and inadequate community support. Significant inter-related barriers exist at the individual, provider, and system levels. Strategies to improve access include targeting social programs and mental health services, expanding Medicaid eligibility/enrollment, promoting community-based organizations, enforcing the use of trained medical interpreters, and improving cultural competency.


The fuzzy crystallization algorithm: a new approach to complex systems modeling.
A new identification method for fuzzy modeling is introduced. Since the method has some analogy with the process of material crystallization in nature, the name of fuzzy crystallization algorithm (FCA) is given to this novel approach. This method accomplishes structure identification and parameter identification at the same time, and possesses the properties of simplicity, flexibility, and high calculation speed. Compared with other modeling strategies, it is easier to construct a model with a specific accuracy. Numerical examples are provided to demonstrate the performance of this approach.


Adapted to flee famine: adding an evolutionary perspective on anorexia nervosa.
Anorexia nervosa (AN) is commonly attributed to psychological conflicts, attempts to be fashionably slender, neuroendocrine dysfunction, or some combination of these factors. Considerable research reveals these theories to be incomplete. Psychological and societal factors account for the decision to diet but not for the phenomenology of the disorder; theories of biological defects fail to explain neuroendocrine findings that suggest coordinated physiological mechanisms. This article presents evidence that AN's distinctive symptoms of restricting food, denial of starvation, and hyperactivity are likely to be evolved adaptive mechanisms that facilitated ancestral nomadic foragers leaving depleted environments; genetically susceptible individuals who lose too much weight may trigger these archaic adaptations. This hypothesis accounts for the occurrence of AN-like syndromes in both humans and animals and is consistent with changes observed in the physiology, cognitions, and behavior of patients with AN.


Establishment of the Muscle-Tendon Junction During Thorax Morphogenesis in Drosophila Requires the Rho-Kinase.
The assembly of the musculoskeletal system in Drosophila relies on the integration of chemical and mechanical signaling between the developing muscles with ectodermal cells specialized as "tendon cells." Mechanical tension generated at the junction of flight muscles and tendon cells of the notum epithelium is required for muscle morphogenesis, and is balanced by the epithelium in order to not deform. We report that Drosophila Rho kinase (DRok) is necessary in tendon cells to assemble stable myotendinous junctions (MTJ), which are required for muscle morphogenesis and survival. In addition, DRok is required in tendon cells to maintain epithelial shape and cell orientation in the notum, independently of chascon (chas). Loss of DRok function in tendon cells results in mis-orientation of tendon cell extensions and abnormal accumulation of Thrombospondin and βPS-integrin, which may cause abnormal myotendinous junction formation and muscle morphogenesis. This role does not depend exclusively on nonmuscular Myosin-II activation (Myo-II), indicating that other DRok targets are key in this process. We propose that DRok function in tendon cells is key to promote the establishment of MTJ attachment and to balance mechanical tension generated at the MTJ by muscle compaction.


Acromelic frontonasal dysostosis and ZSWIM6 mutation: phenotypic spectrum and mosaicism.
Acromelic frontonasal dysostosis (AFND) is a distinctive and rare frontonasal malformation that presents in combination with brain and limb abnormalities. A single recurrent heterozygous missense substitution in ZSWIM6, encoding a protein of unknown function, was previously shown to underlie this disorder in four unrelated cases. Here we describe four additional individuals from three families, comprising two sporadic subjects (one of whom had no limb malformation) and a mildly affected female with a severely affected son. In the latter family we demonstrate parental mosaicism through deep sequencing of DNA isolated from a variety of tissues, which each contain different levels of mutation. This has important implications for genetic counselling.


Overexpression, crystallization and preliminary X-ray crystallographic analysis of Nudix hydrolase Orf141 from Escherichia coli K-1.
Nudix hydrolases are a family of proteins that contain the characteristic amino-acid sequence GX(5)EX(7)REUXEEXGU (where U is usually I, L or V), the Nudix signature sequence. They catalyze the hydrolysis of a variety of nucleoside diphosphate derivatives such as nucleoside triphosphates, nucleotide sugars, ADP-ribose, dinucleotide coenzymes, diadenosine oligophosphates and capped RNAs. Recently, three new Nudix hydrolases have been found from Escherichia coli; one of them is Orf141, which cleaves pyrimidine deoxynucleoside triphosphates. Orf141 was cloned directly from E. coli K1 strain and was overexpressed in E. coli without any extra residues. Orf141 crystals were successfully obtained using polyethylene glycol 1500 as a precipitant at 285 K. X-ray diffraction data were collected to 3.1 A resolution using synchrotron radiation. The crystal is a member of the rhombohedral space group H32, with unit-cell parameters a = b = 182.2, c = 62.3 A, alpha = 90, beta = 90, gamma = 120 degrees (hexagonal setting). Two or three monomers are likely to be present in the asymmetric unit, with corresponding V(M) values of 2.92 and 1.95 A3 Da(-1) and solvent contents of 57.9 and 36.9%, respectively.


Membrane composition and cellular responses to fatty acid intakes and factors explaining the variation in response.
The lipid membrane bilayer undergoes continuous changes, and its lipid composition is both adaptive and highly varied, with substantial molecular variety. The balance of dietary fats, namely saturated versus unsaturated, and polyunsaturated fatty acids (PUFA) of the n-6 series versus those of the n-3 series, may change membrane composition thus affecting membrane order, intracellular signaling processes, and gene expression. As a consequence, changes in the production of both lipid and peptide mediators influencing the individual adaptive responses take place. More than that of all the other fatty acids, the n-3 PUFA composition of cell membranes depends on their dietary intake. n-3 PUFA levels in cell membranes are related to both inflammatory and immune diseases, possibly by downregulating the expression of genes involved in their synthesis and maybe the pathogenesis of processes associated with the disease itself. The interindividual variability of DNA sequences involved in the synthesis of long-chain PUFA may explain differences in responses to their dietary contribution in regulating the risk of disease. Lifestyle factors (such as smoking and alcohol consumption) may in turn negatively impact PUFA metabolism. Accordingly, different amounts of dietary PUFA may be necessary to meet the requirements for these nutrients in development and disease prevention on an individual basis.