Preliminary report on harmonization of features extraction process using the ComBat tool in the multi-center "Blue Sky Radiomics" study on stage III unresectable NSCLC.
In the retrospective-prospective multi-center "Blue Sky Radiomics" study (NCT04364776), we plan to test a pre-defined radiomic signature in a series of stage III unresectable NSCLC patients undergoing chemoradiotherapy and maintenance immunotherapy. As a necessary preliminary step, we explore the influence of different image-acquisition parameters on radiomic features' reproducibility and apply methods for harmonization. We identified the primary lung tumor on two computed tomography (CT) series for each patient, acquired before and after chemoradiation with i.v. contrast medium and with different scanners. Tumor segmentation was performed by two oncological imaging specialists (thoracic radiologist and radio-oncologist) using the Oncentra Masterplan® software. We extracted 42 radiomic features from the specific ROIs (LIFEx). To assess the impact of different acquisition parameters on features extraction, we used the Combat tool with nonparametric adjustment and the longitudinal version (LongComBat). We defined 14 CT acquisition protocols for the harmonization process. Before harmonization, 76% of the features were significantly influenced by these protocols. After, all extracted features resulted in being independent of the acquisition parameters. In contrast, 5% of the LongComBat harmonized features still depended on acquisition protocols. We reduced the impact of different CT acquisition protocols on radiomic features extraction in a group of patients enrolled in a radiomic study on stage III NSCLC. The harmonization process appears essential for the quality of radiomic data and for their reproducibility. ClinicalTrials.gov Identifier: NCT04364776, First Posted:April 28, 2020, Actual Study Start Date: April 15, 2020, https://clinicaltrials.gov/ct2/show/NCT04364776 .


The importance of the evolutionary heritage of locomotion on flat ground in small mammals for the development of arboreality.
The earliest representatives of the mammalian stem line were small. Recent small mammals preserving their morphology possess rather similar kinematic and dynamic locomotor patterns, even if they are not closely related. For a small animal, the mechanics of locomotion on a large branch is comparable to locomotion on flat ground. Combining these informations, it seems sensible to start a discussion on the origins of arboreality with a detailed analysis of the locomotion of small mammals on flat ground. For this purpose, the kinematics of twelve species of mammals were observed using cineradiography, a "general limb" of small mammals was derived as a principle, and its interactions with the trunk were analyzed. These data form the basis for a theoretical upscaling of the motion patterns in arboreal animals, revealing that the transfer of torques between animal and branch becomes unavoidable, thus making the use of prehensile hands advantageous, which by their tendency of distal concentration of muscle masses force the need to change the basic kinematic patterns.


Primary renal magnesium wasting: an unusual clinical picture of exercise-induced symptoms.
Magnesium is one of the most abundant cations in the human body and plays a key role as a metabolic enzyme cofactor and regulatory ion for neurons and cardiomyocytes. Hypomagnesemia due to isolated primary renal magnesium wasting is a rare clinical condition typically associated with neurological hyperexcitability. Exercise-related gastrointestinal symptoms are caused by ischemic, mechanical, or neurohormonal changes. The role of hypomagnesemia in gastrointestinal symptoms is not well understood. We present a case of a 15-year-old male who presented with exercise-induced abdominal pain, nausea, and vomiting, who was found to have profound hypomagnesemia and inappropriately elevated fractional excretion of magnesium (FEMg). Testing for multiple intrinsic and extrinsic etiologies of renal magnesium wasting was inconclusive. He was diagnosed with primary renal magnesium wasting and his symptoms resolved acutely with intravenous magnesium sulfate and with long-term oral magnesium chloride. Primary renal magnesium wasting is a rare clinical entity that can cause extreme hypomagnesemia. It has not been associated previously with exercise-induced gastrointestinal symptoms. The effects of hypomagnesemia on the human gastrointestinal tract are not well established. This case offers unique insights into the importance of magnesium homeostasis in the gastrointestinal tract. Exercise-induced splanchnic hypoperfusion may contribute to gastrointestinal symptoms observed in this chronically hypomagnesemic patient.


Inhaler Use Technique in Chronic Obstructive Pulmonary Disease Patients: Errors, Practices and Barriers.
Background Inhaled medications are the main therapeutic treatment of chronic obstructive pulmonary disease (COPD) and inhaler technique remained important that can increase medication efficacy, reducing dose and side effects. Poor inhaler technique is multi-factorial and the quality of inhaler technique has not previously assessed in Pakistan. We conducted a study to examine a range of competing factors that impact COPD patient willingness, practices, and preference in using their inhalers. Methods A cross-sectional of 765 patients with COPD were interviewed and assessed by qualitative questionnaires. Objective inhalation technique and steps assessment was performed; satisfaction, preferences, perception, and practice of different types of inhaler devices were evaluated at a single cross-sectional visit at the study enrolment. Results The study included 765 participants of mean age 58.7 years (SD ±7.8); 32% males and 68% females. Almost all of the females were exposed to biomass fuel smoke exposure (99%) and pipe (Huka) smokers 53%, while most male participants were cigarette smokers (92%). Only 6.3% of participants were able to perform correct steps of inhaler use, and few educated patients completed 7-steps. 66% of patients were using dry powder inhalers (DPI) inhaler devices and mostly performed the steps 1, 2, and 4 (98%) correctly, while 44% who were using metered-dose inhalers (MDI) completed only steps 2 and 4 correctly (88%). The majority of participants reported the particular inhaler devices was prescribed by the visiting consultants (54%). Interestingly, they were using two inhalers together (47%) relieving symptoms of dyspnea (83%) and cough (73%). The inhaler use technique was demonstrated to most of the patients by the pharmacy salesman (38.4%), while 15.8% reported that their doctors taught them the inhaler technique. 54.2% reported reason for poor adherence to inhaler use as they understand it might not work lately and 75.2% were not aware of any side effects associated with the regular use of an inhaler. Conclusions Poor inhaler technique is highly prevalent and the associated errors did not appear to be dependent on device type. Most of the participants had not receive proper training about the correct use and were not involved in decision making about the choice of inhaler device.


Aqueous alkylchloroformate derivatisation and solid-phase microextraction: determination of amphetamines in urine by capillary gas chromatography.
The alkylchloroformate derivatisation and solid-phase microextraction of amphetamine and methamphetamine directly in urine samples prior to capillary gas chromatographic analysis is described. The alkylchloroformate reagent was added to the urine sample, which was adjusted to pH 10.8, and an internal standard was added. The resulting products were water-stable carbamates that were extracted without organic solvent. The polydimethylsiloxane coated fibre was inserted into the modified sample and agitated for 14 min. The fibre with the extracted derivatisation products was injected into the capillary gas chromatograph. The extracted carbamates were evaporated at 300 degrees C in the split-splitless injection port of the gas chromatograph, separated on a methylsilicone capillary column and detected by either a nitrogen-phosphorus detector or by mass spectrometry. The method was shown to be reproducible with a detection limit of 50 ng/ml of amphetamine and methamphetamine in urine.


Proteome analysis and serological characterization of surface-exposed proteins of Rickettsia heilongjiangensis.
Rickettsia heilongjiangensis, the agent of Far-Eastern spotted fever (FESF), is an obligate intracellular bacterium. The surface-exposed proteins (SEPs) of rickettsiae are involved in rickettsial adherence to and invasion of host cells, intracellular bacterial growth, and/or interaction with immune cells. They are also potential molecular candidates for the development of diagnostic reagents and vaccines against rickettsiosis. R. heilongjiangensis SEPs were identified by biotin-streptavidin affinity purification and 2D electrophoreses coupled with ESI-MS/MS. Recombinant SEPs were probed with various sera to analyze their serological characteristics using a protein microarray and an enzyme-linked immune sorbent assay (ELISA). Twenty-five SEPs were identified, most of which were predicted to reside on the surface of R. heilongjiangensis cells. Bioinformatics analysis suggests that these proteins could be involved in bacterial pathogenesis. Eleven of the 25 SEPs were recognized as major seroreactive antigens by sera from R. heilongjiangensis-infected mice and FESF patients. Among the major seroreactive SEPs, microarray assays and/or ELISAs revealed that GroEL, OmpA-2, OmpB-3, PrsA, RplY, RpsB, SurA and YbgF had modest sensitivity and specificity for recognizing R. heilongjiangensis infection and/or spotted fever. Many of the SEPs identified herein have potentially important roles in R. heilongjiangensis pathogenicity. Some of them have potential as serodiagnostic antigens or as subunit vaccine antigens against the disease.


Malnutrition and Dietary Habits Alter the Immune System Which May Consequently Influence SARS-CoV-2 Virulence: A Review.
COVID-19, resulting from the SARS-CoV-2 virus, is a major pandemic that the world is fighting. SARS-CoV-2 primarily causes lung infection by attaching to the ACE2 receptor on the alveolar epithelial cells. However, the ACE2 receptor is also present in intestinal epithelial cells, suggesting a link between nutrition, virulence and clinical outcomes of COVID-19. Respiratory viral infections perturb the gut microbiota. The gut microbiota is shaped by our diet; therefore, a healthy gut is important for optimal metabolism, immunology and protection of the host. Malnutrition causes diverse changes in the immune system by repressing immune responses and enhancing viral vulnerability. Thus, improving gut health with a high-quality, nutrient-filled diet will improve immunity against infections and diseases. This review emphasizes the significance of dietary choices and its subsequent effects on the immune system, which may potentially impact SARS-CoV-2 vulnerability.


Synthesis and Catalytic Property of Ribonucleoside-Derived Carbon Dots.
Exploring appropriate precursors has been proposed to be a promising strategy for the creation of artificial enzymes that are emerging as alternatives of natural enzymes. Herein, inspired by the catalytic activities of ribose nucleic acid, using ribonucleosides as precursors including adenosine, guanosine, cytidine, and uridine, respectively, four carbonic aggregates, namely, carbon dots (A-CDs, G-CDs, C-CDs, and U-CDs) to mimic artificial enzymes are synthesized. All the CDs show a planar graphene-like structure and thus can intercalatively bind with DNA double helix. Different from the other three CDs, the uridine-derived U-CDs exhibit unique catalytic property, which can mediate the topological transformation of DNA from supercoiled to nicked open-circular conformation. U-CDs can catalyze oxidation of O2 to generate singlet oxygen 1 O2 via a Haber-Weiss reaction, and consequently mediate oxidative cleavage of phosphate backbone in DNA and release the torsional energy stored in supercoiled DNA. Explorations reveal that the unique highly active oxygenated species, namely, quinone groups that are on the edge of U-CDs, play a key role in the catalytic production of 1 O2 . This work represents a new insight that using natural biomolecules in living systems as precursors can create new species beyond life.


An evaluation of sodium bicarbonate chewing gum in reducing dental plaque and gingivitis in conjunction with regular toothbrushing.
The purpose of the present study was to determine the ability of a chewing gum containing 5% sodium bicarbonate to remove dental plaque and reduce gingivitis when used as a supplement to daily toothbrushing. The study group consisted of 88 adults with moderate gingivitis. Participants were divided into 4 groups and instructed to chew the study gum 0 (control), 1, 2, or 3 times daily for 1 month in addition to regular daily toothbrushing. Chewing sodium bicarbonate-containing gum significantly (P < .05) reduced plaque after 1 week, with progressively greater reductions occurring after 2 and 4 weeks of gum chewing. No correlation was observed between plaque reduction and the number of times per day that the gum was chewed. By week 4, plaque reduction of approximately 16% was achieved in all groups using the gum as compared with the control group. Reductions in gingivitis were observed in all participants who chewed the gum, and these reductions achieved statistical significance by week 4. Slightly greater improvements in gingivitis were achieved in participants who chewed the gum 2 or 3 times daily as compared with the control group and those who chewed the gum once daily. No adverse effects on the oral tissues were observed in any of the participants for the duration of the study. In conclusion, regular use of a chewing gum containing 5% sodium bicarbonate appears safe and effective for the removal of dental plaque and reduction of gingivitis when used in conjunction with daily toothbrushing.


Direct induction of chondrogenic cells from human dermal fibroblast culture by defined factors.
The repair of large cartilage defects with hyaline cartilage continues to be a challenging clinical issue. We recently reported that the forced expression of two reprogramming factors (c-Myc and Klf4) and one chondrogenic factor (SOX9) can induce chondrogenic cells from mouse dermal fibroblast culture without going through a pluripotent state. We here generated induced chondrogenic (iChon) cells from human dermal fibroblast (HDF) culture with the same factors. We developed a chondrocyte-specific COL11A2 promoter/enhancer lentiviral reporter vector to select iChon cells. The human iChon cells expressed marker genes for chondrocytes but not fibroblasts, and were derived from non-chondrogenic COL11A2-negative cells. The human iChon cells formed cartilage but not tumors in nude mice. This approach could lead to the preparation of cartilage directly from skin in human, without going through pluripotent stem cells.


The origin of the piezoelectric effect in pyroelectric crystals.
The physical mechanism of piezoelectricity arising in crystals of all pyroelectric classes is described and discussed in detail. The piezoelectric effect of these crystals is postulated to be a consequence of changes in their spontaneous polarization under the impact of external forces (electric fields, mechanical stresses). This study shows which piezoelectric coefficients do exist in pyroelectric crystals. Both the direct piezoeffect--generation of electric polarization under mechanical stresses--and the inverse piezoeffect--crystal deformations caused by the application of an electric field--are considered. Specifically, the analysis performed suggests that crystals of classes 6, 4, and 3 may lack d14 and d25 piezo modules, the existence of which is, in principle, allowed by the symmetry of the crystals, but which do not actually exist because of the accidental cancellation of requisite "piezo-generating" elastic compliance coefficients.


An Academic-Practice Partnership to Advance Million Hearts®.
An academic-practice partnership between a college department of nursing, the YMCA, and one health system was developed to provide student learning opportunities in cardiovascular disease prevention, while advancing the goal of Million Hearts®. Using The Ohio State University College of Nursing's Million Hearts Fellowship Module, students learned to provide Million Hearts screenings, educate and coach participants in the college and greater community, and deliver a free home blood pressure monitor. Pre- and postscores were obtained to assess change in students' knowledge and participants' blood pressure, lifestyle scores, and perceived stress scores. A statistically significant improvement in mean participant blood pressure and lifestyle scores was observed. This academic-practice partnership provided an opportunity for students to learn about prevention within a national, population health initiative and for participants to achieve measurable, healthy outcomes. The college's participation in a national Million Hearts consortium enabled practice partners to prioritize cardiovascular disease prevention in the community. [J Nurs Educ. 2021;60(2):103-106.].


The characteristics of pressure injury photographs from the electronic health record in clinical settings.
To analyse and understand the characteristics of pressure injury images stored in the electronic health record. To improve the quality of pressure injury documentation, photographing pressure injuries and storing the images in the electronic health record are standard practices in many hospitals. As new technologies develop, the utilisation of computer-assisted image processing makes automatic measurement of pressure injury size and tissue segmentation through pressure injury images possible. The translation of new technological developments to pressure injury photography conducted in clinical environments faces obstacles such as the complexity of conditions in which photographs are taken. A cross-sectional descriptive study. A set of 360 pressure injury images were obtained from a hospital in western Pennsylvania. These images were taken in clinical settings during daily wound care service. The authors reviewed the pressure injury images to analyse the relative position of the pressure injury in the images, the shooting angle of the digital camera and the clinical objects in the background. Only 5.9% of the pressure injury images were confined to only the wound region. In 80.1% of the images, the pressure injury is located in the central part of the image. In 54.0% of the images, the lens of the digital camera was not pointed perpendicularly to the plane of the pressure injury. Bedside wound assessment of pressure injuries and assessment from photographs of pressure injuries display reasonable agreement with pressure injury staging. To extract wound information (e.g., size and tissue type) from pressure injury images through novel image processing technologies, the characteristics of pressure injury images in clinical settings should be better understood during the development of tools for pressure injury image processing. Our results can help image processing experts understand wound photography characteristics to shorten the gap between laboratory and clinical environments when translating new image processing technologies.


Plasma cell granuloma of the larynx as a cause of sudden asphyxial death.
A unique case of plasma cell granuloma of the larynx associated with sudden death in a young HIV-positive woman is described. The plasma cell infiltration fulfilled the criteria for plasma cell granuloma, showing characteristic histologic and immunohistochemical features (polyclonality). A review of the most recent literature is provided.


Examination of a CRP first approach for the detection of postoperative complications in patients undergoing surgery for colorectal cancer: A pragmatic study.
The aim of the present study was to examine whether a C-reactive protein (CRP) first approach would improve the detection rate of postoperative complications by CT.CRP is a useful biomarker to identify major complications following surgery for colorectal cancer.Patients with histologically confirmed colorectal cancer, who underwent elective surgery between 2008 and 2015 at a single centre were included. Exceeding the established CRP threshold of 150 mg/L on postoperative day (POD) 4 was recorded. Results of CT performed between postoperative days 4 and 14 were recorded.Four hundred ninety-five patients were included. The majority were male (58%), over 65 (68%), with node-negative disease (66%) and underwent open surgery (70%). Those patients who underwent a CT scan (n = 93), versus those who did not (n = 402), were more likely to have a postoperative complication (84% vs 35%, P < 0.001), infective complication (67% vs 21%, P < 0.001), and anastomotic leak (17% vs 2%, P < 0.001). In patients who did not undergo a CT scan (n = 402) exceeding the CRP threshold (n = 117) on POD 4 was associated with a higher rate of postoperative complication (50% vs 29%, P < 0.001), infective complications (36% vs 15%, P < 0.001), and anastomotic leak (4% vs 0.5%, P = 0.009). In patients who did undergo a CT scan (n = 93) exceeding the CRP threshold (n = 53) on POD 4 was associated with earlier CT (median POD 6 vs 8, P = 0.001) but not postoperative complications.A CRP first approach resulted in earlier and improved detection of complications by CT following surgery for colorectal cancer.


Circulatory and vascular changes after aneurysmal subarachnoid hemorrhage.
Delayed cerebral ischemia (DCI) is a major complication that afflicts approximately 30% of patients who suffer an aneursymal subarachnoid hemorrhage (SAH). DCI is often associated with neurological infarction, poor outcome and mortality. Though the pathogenesis of DCI is not yet clear, it is traditionally been attributed to angiographic vasospasm. Unfortunately, clinical trials based on this premise have mostly been disappointing, predominantly unable to prevent ischemic damage and improve patient outcome despite reducing angiographic vasospasm. More recently, increasing concern that vasospasm could not fully account for DCI development has incited novel proposals as to the pathogenesis of DCI. A general theme exists among these theories (microcirculatory constriction, cortical spreading depression, blood brain barrier breakdown, microthrombosis) in that a majority seems to revolve around dysfunction and changes to the microvasculature. This purpose of this review was then to juxtapose macrovascular and microvascular changes after SAH, and provide an overview of current and prospective treatments.


Assessing individual differences in constructive versus destructive responses to anger across the lifespan.
Scenario-based, self-report measures were developed to assess how people characteristically experience and manage anger from middle childhood through adulthood. The Anger Response Inventories (ARIs) for children, adolescents, and adults each assess (a) anger arousal, (b) intentions, (c) cognitive and behavioral responses, and (d) Long-term consequences. Several independent studies provide support for the reliability and validity of the ARIs. Theoretically consistent patterns of correlations were observed with (a) global self-report measures of hostility, aggression, and anger-management strategies (adult version); (b) teacher reports of behavioral and emotional adjustment (child and adolescent versions); and (c) self- and family-member reports of behaviors on specific anger episodes (adolescent and adult versions). Findings from additional personality and developmental studies are summarized, further supporting construct validity.


Bodotria jejuensis sp. nov. (Crustacea, Cumacea, Bodotriidae), a new Korean cumacean.
A new species of Cumacea belonging to the genus Bodotria Goodsir, 1843 was collected from the Jeju-do Island, Korea. The new speices, Bodotria jejuensis sp. nov. is similar to B. similis Calman, 1907, B. rugosa Gamô, 1963, B. carinata Gamô, 1964, and B. biplicata Gamô, 1964 in having a pitted carapace, prominent dorso-lateral carina, and unarticulated endopod of uropod. However, longish elliptical shape of carapace, well-developed dorso-lateral carina and distinct lateral ridge are the major characteristics which serve to distinguish the new species from its congeners. The new species is fully illustrated and extensively compared with related species. A key to the Korean Bodotria species is also provided.


Random Forest Algorithm-Based Ultrasonic Image in the Diagnosis of Patients with Dry Eye Syndrome and Its Relationship with Tear Osmotic Pressure.
The study was to investigate the diagnostic value of ultrasound based on the random forest segmentation algorithm for dry eye disease and the relationship between dry eye degree and tear osmotic pressure. Specifically, 100 patients with dry eye syndrome were selected as the research subjects, and they were divided into group A (conventional ultrasonic detection) and group B (ultrasonic detection based on the random forest segmentation algorithm), with 50 patients in each group. An ultrasonic measurement was used as the gold standard to evaluate the effect of ultrasonic diagnosis. The degree of dry eye was determined by Ocular Surface Disease Index (OSDI) Questionnaire and DR-1 tear film lipid layer (TFLL) test. The tear osmotic pressure was measured, and the relationship between the degree of dry eye disease and the tear osmotic pressure was analyzed. The results showed that the ultrasonic imaging effect and each index based on random forest algorithm were better than the traditional graph cut algorithm. The average central corneal thickness (CCT) values of group A and group B were (27.8 ± 30.6) μm and (29.1 ± 30.9) μm, respectively. 95% confidence interval was 22.7-34.2 μm. In patients with moderate dry eye, the average CCT measured in group A was (-6.31 ± 2.82) μm, and that in group B was (-6.45 ± 3.06) μm. The 95% confidence interval of the difference between the two is -7.66~-5.43 μm. In patients with severe dry eye, the average CCT was (-3.78 ± 1.13) μm in group A and (-7.09 ± 2.05) μm in group B (P < 0.05). The 95% confidence interval of the difference between the two is -7.05~ -5.11 μm. In spearman correlation analysis, tear osmotic pressure increased with dry eye severity. There was a statistically significant difference between the moderate and the severe (P < 0.05). Tear osmotic pressure can be a rapid diagnostic index of dry eye severity. Ultrasound based on the random forest segmentation algorithm has high clinical application value in the diagnosis of dry eye syndrome.


Neonatal hyperoxia increases airway reactivity and inflammation in adult mice.
Supplemental O2 to treat bronchopulmonary dysplasia (BPD) in premature infants, is a major risk factor producing alteration in lung function, airway reactivity, and predisposition to respiratory infections. This study explores inflammatory and airway responses following neonatal hyperoxia in adult mice. Newborn mouse litters were randomized to 85% O2 or room air (RA) on P3 for 12 days; mice were sacrificed either on P15 or at 15 weeks following recovery in RA. Airway hyper reactivity (AHR) was assessed in vivo (8 and 12 weeks) and in vitro (15 weeks) with methacholine; Lung and BAL were assayed for inflammatory mediators, cell counts, CD3 immunohistochemistry, and histopathology. Hyperoxic mice had increased airway reactivity at baseline and following methacholine challenge in vivo (8 and 12 weeks); isolated tracheal rings had a significantly higher constriction response to methacholine in vitro compared to RA group. Inflammatory markers were higher at 2 weeks (MCP-1, IL-12, INF-γ) and at 15 weeks (LTB4 , VEGF); Lipoxin-A4 was lower in the hyperoxia group at both time points. Increased airway smooth muscle thickness and angiogenesis in the lung was seen at 15 weeks. Hyperoxic lungs exhibited alveolar simplification at 2 and 15 weeks. Absolute lymphocyte count was higher in lavage fluid with an increased CD3 cell count at 15 weeks suggesting persistent inflammation in adult mice following neonatal hyperoxia. Exposure to hyperoxia in newborn mice increases long-term airway reactivity with persistent lung inflammation associated with a marked increase in lymphocytes, suggesting long-term consequences in adults. Pediatr Pulmonol. 2016;51:1131-1141. © 2016 Wiley Periodicals, Inc.


Black tea volatiles fingerprinting by comprehensive two-dimensional gas chromatography - Mass spectrometry combined with high concentration capacity sample preparation techniques: Toward a fully automated sensomic assessment.
Tea prepared by infusion of dried leaves of Camellia sinensis (L.) Kuntze, is the second world's most popular beverage, after water. Its consumption is associated with its chemical composition: it influences its sensory and nutritional quality addressing consumer preferences, and potential health benefits. This study aims to obtain an informative chemical signature of the volatile fraction of black tea samples from Ceylon by applying the principles of sensomics. In particular, several high concentration capacity (HCC) sample preparation techniques were tested in combination with GC×GC-MS to investigate chemical signatures of black tea volatiles. This platform, using headspace solid phase microextraction (HS-SPME) with multicomponent fiber as sampling technique, recovers 95% of the key-odorants in a fully automated work-flow. A group 123 components, including key-odorants, technological and botanical tracers, were mapped. The resulting 2D fingerprints were interpreted by pattern recognition tools (i.e. template matching fingerprinting and scripting) providing highly informative chemical signatures for quality assessment.


Using the tenets of the problem-centered systems therapy of the family (PCSTF) to teach the McMaster Approach to family therapists.
This article describes the videoconferencing training of a group of family therapists in the McMaster Approach to evaluating and treating families. A discussion of the key tenets of the McMaster Approach lays the groundwork for how these tenets were applied to training in a residential treatment agency for adolescents. The article serves as an example of how videoconference technology can facilitate extended training, even from a distance.


Effect of house dust mite immunotherapy on interleukin-10-secreting regulatory T cells in asthmatic children.
Subcutaneous specific immunotherapy has been demonstrated to be capable of inducing T-cell regulatory response. Interleukin-10 (IL-10) plays a crucial role in inducing allergen-specific tolerance. However the reports of the changes of IL-10 in house dust mite (HDM)-specific immunotherapy were varied. The aim of this study was to evaluate the function of IL-10-secreting regulatory T cells in asthma children successfully treated with HDM immunotherapy. Peripheral blood mononuclear cells (PBMCs) were isolated from 27 patients following 1.5 - 2 years of HDM-specific immunotherapy (SIT, SIT group) and from 27 matched treated asthmatic children allergic to HDM (asthma group). After 48 hours of in vitro stimulation with HDM extracts, IL-10-secreting regulatory T cells were measured by four colour flow cytometry. Sera were tested for allergen-specific IgG(4) and IgE using the Immuno CAP 100 assay. PBMCs from children undergoing immunotherapy following HDM extracts stimuli produced significantly more IL-10 compared with the asthma group. The frequency of iTreg cells and aTreg cells increased in SIT group after HDM stimulation, while it was not affected in the asthma group. Among the iTreg cells and aTreg cells, the frequency of CD4(+)CD25(-)Foxp3(-)IL-10(+) Treg cells increased the most which was 2 times higher than that in unstimulated cultures in SIT group. The levels of HDM-specific IgG(4) of SIT group was significiently higher compared with asthma group, but there was no correlation of the levels of HDM-specific IgG(4) and IL-10 secreting Treg cells. HDM-specific immunotherapy can successfully upregulate the frequency of IL-10-secreting Treg cells. CD4(+)CD25(-)Foxp3(-)IL-10(+) Treg cells may play a key role in inducing the immune tolerance in HDM-specific immunotherapy.


Expanding the Pathogenic Potential Concept To Incorporate Fulminancy, Time, and Virulence Factors.
The pathogenic potential (PP) concept posits that all microorganisms have some pathogenic potential that can be calculated by an equation that includes the fraction symptomatic, inoculum, and mortality fraction. The PP concept dispenses with characterizing microbes as pathogens, nonpathogens, commensals, pathobionts, etc., by providing an alternative approach to the problem of virulence that considers the contributions of both the host and the microbe. Here, the PP concept is extended to incorporate the role of time in virulence by introducing a new parameter, fulminancy, which is a measure of the rapidity of the pathogenic process. Fulminancy allows PP calculations in situations where all hosts are affected equally, but the process occurs later for attenuated strains. Differences in the PP of wild-type and mutant microbes lacking virulence factors can be used to estimate the contribution of virulence factors to the pathogenic process, thus providing a new quantitative approach to these important pathogenicity parameters.


Discovery of the combined oxidative cleavage of plant xylan and cellulose by a new fungal polysaccharide monooxygenase.
Many agricultural and industrial food by-products are rich in cellulose and xylan. Their enzymatic degradation into monosaccharides is seen as a basis for the production of biofuels and bio-based chemicals. Lytic polysaccharide monooxygenases (LPMOs) constitute a group of recently discovered enzymes, classified as the auxiliary activity subgroups AA9, AA10, AA11 and AA13 in the CAZy database. LPMOs cleave cellulose, chitin, starch and β-(1 → 4)-linked substituted and non-substituted glucosyl units of hemicellulose under formation of oxidized gluco-oligosaccharides. Here, we demonstrate a new LPMO, obtained from Myceliophthora thermophila C1 (MtLPMO9A). This enzyme cleaves β-(1 → 4)-xylosyl bonds in xylan under formation of oxidized xylo-oligosaccharides, while it simultaneously cleaves β-(1 → 4)-glucosyl bonds in cellulose under formation of oxidized gluco-oligosaccharides. In particular, MtLPMO9A benefits from the strong interaction between low substituted linear xylan and cellulose. MtLPMO9A shows a strong synergistic effect with endoglucanase I (EGI) with a 16-fold higher release of detected oligosaccharides, compared to the oligosaccharides release of MtLPMO9A and EGI alone. Now, for the first time, we demonstrate the activity of a lytic polysaccharide monooxygenase (MtLPMO9A) that shows oxidative cleavage of xylan in addition to cellulose. The ability of MtLPMO9A to cleave these rigid regions provides a new paradigm in the understanding of the degradation of xylan-coated cellulose. In addition, MtLPMO9A acts in strong synergism with endoglucanase I. The mode of action of MtLPMO9A is considered to be important for loosening the rigid xylan-cellulose polysaccharide matrix in plant biomass, enabling increased accessibility to the matrix for hydrolytic enzymes. This discovery provides new insights into how to boost plant biomass degradation by enzyme cocktails for biorefinery applications.


Proluciferin acetals as bioluminogenic substrates for cytochrome P450 activity and probes for CYP3A inhibition.
Cytochrome P450 (P450) assays use probe substrates to interrogate the influence of new chemical entities toward P450 enzymes. We report the synthesis and study of a family of bioluminogenic luciferin acetal substrates that are oxidized by P450 enzymes to form luciferase substrates. The luciferin acetals were screened against a panel of purified P450 enzymes. In particular, one proluciferin acetal has demonstrated sensitive and selective CYP3A4-catalyzed oxidation to a luciferin ester-K(m) and k(cat) are 2.88 μM and 5.87 pmol metabolite · min(-1) · pmol enzyme(-1), respectively. The proluciferin acetal was used as a probe substrate to measure IC(50) values of known inhibitors against recombinant CYP3A4 or human liver microsomes. IC(50) values for the known inhibitors correlate strongly with IC(50) values calculated from the traditional high-performance liquid chromatography-based probe substrate testosterone. Luciferin acetals are rapidly oxidized to unstable hemi-orthoesters by CYP3A resulting in luciferin esters and, therefore, are conducive to simple rapid CYP3A bioluminescent assays.


Primary structure of human pancreatic protease E determined by sequence analysis of the cloned mRNA.
Although protease E was isolated from human pancreas over 10 years ago [Mallory, P. A., & Travis, J. (1975) Biochemistry 14, 722-729], its amino acid sequence and relationship to the elastases have not been established. We report the isolation of a cDNA clone for human pancreatic protease E and determination of the nucleic acid sequence coding for the protein. The deduced amino acid sequence contains all of the features common to serine proteases. The substrate binding region is highly homologous to those of porcine and rat elastases 1, explaining the similar specificity for alanine reported for protease E and these elastases. However, the amino acid sequence outside the substrate binding region is less than 50% conserved, and there is a striking difference in the overall net charge for protease E (6-) and elastases 1 (8+). These findings confirm that protease E is a new member of the serine protease family. We have attempted to identify amino acid residues important for the interaction between elastases and elastin by examining the amino acid sequence differences between elastases and protease E. In addition to the large number of surface charge changes which are outside the substrate binding region, there are several changes which might be crucial for elastolysis: Leu-73/Arg-73; Arg-217A/Ala-217A; Arg-65A/Gln-65A; and the presence of two new cysteine residues (Cys-98 and Cys-99B) which computer modeling studies predict could form a new disulfide bond, not previously observed for serine proteases. We also present evidence which suggests that human pancreas does not synthesize a basic, alanine-specific elastase similar to porcine elastase 1.


Abdominal Pain Followed by Altered Mental Status: A Rare Presentation of Guillain Barré Syndrome.
Guillain Barré syndrome (GBS) is an acute inflammatory polyneuropathy with several variants; it usually presents as acute symmetrical muscle weakness with or without bulbar involvement, making it a neurological emergency. In this report, we describe the case of a 39-year-old male who presented with abdominal pain for three days and whose illness became progressively drowsy on the fifth day. Based on clinical assessment, nerve conduction studies, and biochemical, microbiological, and radiological investigations, other causes were ruled out and it was concluded that the patient had hyponatremia secondary to syndrome of inappropriate diuretic hormone secretion (SIADH) due to GBS. Although sensory symptoms like pain or dysaesthesias occurring in the back or extremities are common and may precede motor weakness, abdominal pain remains a very rare presentation of GBS. GBS is usually understood as a "pure" peripheral nervous system disorder but central nervous system (CNS) dysfunction may occur due to metabolic abnormalities (like hyponatremia and CO2 narcosis) or autonomic dysfunction in GBS, its treatment, or due to GBS itself (Anti-GQ1b disease variant).


Immediate Loading of Implants Inserted Through Impacted Teeth in the Esthetic Area: A Series of 10 Cases with up to 7 Years of Follow-up.
The purpose of this case series was to evaluate the survival rate and the incidence of complications of implants inserted and immediately loaded in sites where an impacted tooth was present in the anterior maxillary or mandibular arches (incisor to premolar). The implants were immediately inserted, drilling through the impacted teeth. Site preparation started in the crestal bone and continued into the impacted tooth's enamel and dentin. Seven patients were treated and 11 implants were inserted, 3 in the mandibular arch and 8 in the maxillary arch. All implants healed uneventfully without any adverse clinical or radiographic signs or symptoms, resulting in a success rate of 100%. Once loaded, the implants were in function and monitored for 5 to 7 years. Although more studies and a larger sample size are needed to validate this unconventional procedure, it may be considered as a possible clinical option to overcome invasive procedures and surgical complications related to the extraction of impacted teeth.


Circulatory shear stress induces molecular changes and side population enrichment in primary tumor-derived lung cancer cells with higher metastatic potential.
Cancer is a leading cause of death and disease worldwide. However, while the survival for patients with primary cancers is improving, the ability to prevent metastatic cancer has not. Once patients develop metastases, their prognosis is dismal. A critical step in metastasis is the transit of cancer cells in the circulatory system. In this hostile microenvironment, variations in pressure and flow can change cellular behavior. However, the effects that circulation has on cancer cells and the metastatic process remain unclear. To further understand this process, we engineered a closed-loop fluidic system to analyze molecular changes induced by variations in flow rate and pressure on primary tumor-derived lung adenocarcinoma cells. We found that cancer cells overexpress epithelial-to-mesenchymal transition markers TWIST1 and SNAI2, as well as stem-like marker CD44 (but not CD133, SOX2 and/or NANOG). Moreover, these cells display a fourfold increased percentage of side population cells and have an increased propensity for migration. In vivo, surviving circulatory cells lead to decreased survival in rodents. These results suggest that cancer cells that express a specific circulatory transition phenotype and are enriched in side population cells are able to survive prolonged circulatory stress and lead to increased metastatic disease and shorter survival.


Nutritive blood flow improves interstitial glucose and lactate exchange in perfused rat hindlimb.
Microdialysis was used to assess the interstitial concentrations of glucose and lactate in the constant-flow-perfused rat hindlimb under varying levels of nutritive flow controlled by vasoconstrictors. Increased nutritive flow was achieved by norepinephrine (NE) or angiotensin II (ANG II) and decreased nutritive flow by serotonin (5-HT). NE and ANG II increased oxygen and glucose uptake as well as hindlimb lactate release by 50%. 5-HT decreased oxygen uptake by 15% but had no significant effect on glucose uptake or hindlimb lactate release. Microdialysis recovery of glucose and lactate was significantly elevated by NE and ANG II and decreased by 5-HT. The calculated interstitial concentration of glucose was increased by NE and ANG II but decreased by 5-HT. The interstitial concentration of lactate was decreased by NE and ANG II but increased by 5-HT. In all cases, nitroprusside reversed the effects of the vasoconstrictors. These data indicate that increased nutritive blood flow enhances the exchange of glucose and lactate by improving the supply of glucose to and the removal of lactate from the interstitium.


Creating a note classification scheme for a multi-institutional electronic medical record.
How notes are categorized in an electronic medical record (EMR) influences how rapidly users can locate documents and enter new ones, whether algorithmic search for chart deficiencies is possible, and the ease of incorporating collections of existing notes. We balanced these competing needs when developing a note classification scheme for the Online Record of Clinical Activity (ORCA) electronic medical record at the University of Washington.


Evaluation of pain management documentation.
Accurate and consistent documentation of pain management, including patient responses regarding improvement in pain scores, is essential for improving patient care. The objective of the project was to evaluate the current prescribing patterns and to review the current documentation for opioid-managed, chronic pain patients in an academic continuity of care medicine clinic. Retrospective data were extracted from currently managed adult, opioid patients to evaluate prescribing patterns and to review documentation processes. Results reveal inconsistent to absent documentation with most patients receiving prescriptions from multiple providers. Oxycodone/acetaminophen was the most frequently prescribed analgesic. The results of this evaluation highlight the opportunity for educational intervention and the development of a structured, institution-specific guideline for prescribing and documenting pain management.


Visualization-Based Discovery of Vanin-1 Inhibitors for Colitis.
The main effect of Vanin-1/VNN1 is related to its pantetheinase sulfhydrylase activity, which can hydrolyze pantetheine into pantothenic acid and cysteamine. In recent studies, the enzymatic activity of vanin-1/VNN1 has been found to be essential in the development of many diseases. The study of specific vanin-1/VNN1 inhibitors can give us a deeper understanding of its role in the disease process. In this study, different skeletal inhibitors were designed and synthesized using pyrimidine amide compounds as lead compounds. In order to screen inhibitors intuitively, a fluorescent probe PA-AFC for in vitro evaluation of inhibitors was designed and synthesized in this study, which has good sensitivity and specificity. The bioluminescent probe PA-AL was then used for cellular level and in vivo inhibitor evaluation. This screening method was convenient, economical and highly accurate. Finally, these inhibitors were applied to a mouse colitis model, confirming that vanin-1 is useful in IBD and providing a new therapeutic direction.


Electric stimulation of a transsected nerve does not seem to prevent loss of sensory neurons: an experimental study in cats.
Injury to a sensory nerve often results in a clinically poor long term outcome, possibly as a result of the extensive loss of neurons within the dorsal root ganglia (DRG), which has been shown in several experimental studies. This loss is possibly caused by interruption of the sensory input and axonal transport in the damaged afferent nerve. To investigate the importance of sensory afferent input into a nerve a pulsed electric stimulation was applied on the proximal part of the superficial radial nerve after transsection and microsurgical repair. The purpose was to simulate nerve impulses and thereby mask the severity of the injury. To test this hypothesis a pilot study was undertaken in eight cats. The neuronal tracer showed that the median neuronal loss was 38% of the neurons of the dorsal root ganglia that received afferents from the nerve investigated, which corresponds to the figure in a previous study in which electric stimulation was not used. Artificial sensory stimulation during regeneration in a transsected and repaired peripheral nerve therefore does not seem to reduce neuronal loss.


Interradicular root proximity/fusion: a possible determining factor in regenerating molar furcations.
Both conventional and regenerative approaches have their limitations in correcting furcation defects. Cases of furcation that involve particular anatomical configurations, i.e., interradicular root proximity/fusion, have long been considered relative contraindications for treatments such as root amputation or hemisection. However, there has been little discussion of the role of interradicular root proximity in regenerative procedures. The purpose of this article was to report the clinical significance of the interradicular root relationship in regenerating intrabony defects associated with furcations.


The Effect of Therapeutic Hypothermia after Cardiac Arrest on the Neurological Outcome and Survival-A Systematic Review of RCTs Published between 2016 and 2020.
Therapeutic hypothermia is a treatment used for patients who have suffered cardiorespiratory arrest and remain conscious after the recovery of spontaneous circulation. However, its effectiveness is controversial. The objective of this systematic review is to summarize the scientific evidence available about the effect of therapeutic hypothermia on neurological status and survival in this type of patients. A primary search in CINAHL, CUIDEN, Pubmed, Web of Science, and Scopus databases was carried out. Randomized clinical trials (RCT) published from 2016 to 2020 were selected. 17 studies were selected for inclusion and most relevant data were extracted. Methodological quality was assessed by the RoB tool. Although therapeutic hypothermia is a safe technique with few adverse and manageable effects, it has not shown to improve survival rate and neurological status of adult nor pediatric patients. It is possible that its positive effect on neuroprotection could be achieved only by preventing hyperthermia although further investigation is needed.


COVID-19 Vaccine-Related Adverse Events in Solid Cancer Patients Treated with Immunotherapy.
Little data are available regarding the effects of COVID-19 vaccine in cancer patients undergoing immunotherapy. Thereby, COVID-19 vaccine-related adverse events were monitored through a short questionnaire in solid cancer patients receiving immunotherapy. A total of 95 patients were included in this study. Two doses of vaccines were administered to cancer patients which mainly received Pembrolizumab (51.1%). Respectively 78.2% and 62.2% of patients reported no adverse events after the first and the second dose regardless of the type of vaccine used. Considering the high mortality rate due to COVID-19 among cancer patients, this study demonstrated the good tolerance of COVID-19 vaccine.


IL-37 Attenuates Lung Fibrosis by Inducing Autophagy and Regulating TGF-β1 Production in Mice.
Idiopathic pulmonary fibrosis (IPF) is a progressive and destructive lung disease with a poor prognosis resulting in a high mortality rate. IL-37 is an anti-inflammatory cytokine that inhibits innate and adaptive immunity by downregulating proinflammatory mediators and pathways. However, the exact role of IL-37 in lung fibrosis is unclear. In this study, we found that the IL-37 protein was expressed in alveolar epithelial cells (AECs) and alveolar macrophages in healthy controls but significantly reduced in patients with IPF. IL-37 significantly inhibited oxidative stress-induced primary mouse AEC death in a dose-dependent manner, and knockdown of IL-37 significantly potentiated human lung cancer-derived AEC (A549 cells) death. IL-37 attenuated constitutive mRNA and protein expression of fibronectin and collagen I in primary human lung fibroblasts. IL-37 inhibited TGF-β1-induced lung fibroblast proliferation and downregulated the TGF-β1 signaling pathway. Moreover, IL-37 enhanced beclin-1-dependent autophagy and autophagy modulators in IPF fibroblasts. IL-37 significantly decreased inflammation and collagen deposition in bleomycin-exposed mouse lungs, which was reversed by treatment with the autophagy inhibitor 3-methyladenine. Our findings suggested that a decrease in IL-37 may be involved in the progression of IPF and that IL-37 inhibited TGF-β1 signaling and enhancement of autophagy in IPF fibroblasts. Given its antifibrotic activity, IL-37 could be a therapeutic target in fibrotic lung diseases, including IPF.


Use of intravenous immunoglobulin in severe Clostridium difficile-associated diarrhea.
Clostridium difficile infection is an increasingly common cause of healthcare-acquired diarrhea. There remains substantial morbidity and mortality, even with current modalities of treatment. The aim of our study was to investigate the role of intravenous immunoglobulin (IVIG) on mortality in patients with severe Clostridium difficile-associated diarrhea (CDAD). A retrospective chart review of 21 patients with severe CDAD treated with IVIG in our affiliated hospitals from January 2000 to December 2012 was conducted. As a matching control group, we randomly selected 21 patients meeting the definition of severe CDAD from the same period. Data were compared between these groups using appropriate statistical tests. Patients in the IVIG group were older (69.8 vs 60.9 years, p = 0.05) and had a higher severity score (5.4 vs 3.9, p = 0.02). Mortality was lower among those who received IVIG as compared to the group who did not receive IVIG; however not statistically significant (18.2 vs 22.7%, p = 0.51). Our data demonstrate that although the patients who received IVIG had significantly severe infection, there was no difference in the mortality rate. Prospective controlled studies are needed to assess the true benefit of IVIG in patient with severe Clostridium difficle infection.


Do conspiracy theories efficiently signal coalition membership? An experimental test using the "Who Said What?" design.
Theoretical work in evolutionary psychology have proposed that conspiracy theories may serve a coalitional function. Specifically, fringe and offensive statements such as conspiracy theories are expected to send a highly credible signal of coalition membership by clearly distinguishing the speaker's group from other groups. A key implication of this theory is that cognitive systems designed for alliance detection should intuitively interpret the endorsement of conspiracy theories as coalitional cues. To our knowledge, no previous studies have empirically investigated this claim. Taking the domain of environmental policy as our case, we examine the hypothesis that beliefs framed in a conspiratorial manner act as more efficient coalitional markers of environmental position than similar but non-conspiratorial beliefs. To test this prediction, quota sampled American participants (total N = 2462) completed two pre-registered Who-Said-What experiments where we measured if participants spontaneously categorize targets based on their environmental position, and if this categorization process is enhanced by the use of a conspiratorial frame. We find firm evidence that participants categorize by environmental position, but no evidence that the use of conspiratorial statements increases categorization strength and thus serves a coalitional function.


Preparation of tricyclic lactam model compounds of renieramycin and saframycin anticancer natural products from common intermediate.
Tricyclic lactam model compounds of the left half (ABC ring) of renieramycin and saframycin anticancer natural products were prepared from common intermediate 6a. Readily available alcohol 6a was converted into enamide 8, and this was followed by transformation into 6b through a hydrobromination reaction in a stereoselective manner. Some diastereomers at C-6 to C-11a of the tricyclic lactam model compounds having several functional groups at C-6 were prepared from 6a or 6b in good yields. We presented also an unexpected reductive acetylation of the p-quinone to produce the corresponding 3,4-dehydro derivative.


Development of a prediction model for the risk of recurrent laryngeal nerve lymph node metastasis in thoracolaparoscopic esophagectomy with cervical anastomosis.
There are no effective preoperative diagnostic measures to predict the probability of left and right recurrent laryngeal nerve (RLN) lymph node (LN) metastasis using preoperative clinical data in patients undergoing thoracolaparoscopic esophagectomy with cervical anastomosis. We retrospectively reviewed the clinical data of 1,660 consecutive patients with thoracic esophageal cancer who underwent esophagectomy with cervical anastomosis at the Department of Thoracic Surgery at the First Affiliated Hospital of Zhengzhou University between January 2015 and December 2020. A total of 299 and 343 patients who underwent left (Cohort 1) and right (Cohort 2) RLN LN dissection were included in the final analyses. The analyses were conducted within each cohort. Among the 299 patients in Cohort 1, left RLN LN involvement was found in 41 patients (13.7%). A multivariable analysis showed that age, tumor location, and short axis were significantly associated with RLN LN metastasis (all P<0.05). Among the 343 patients in Cohort 2, right RLN LN involvement was found in 65 patients (19.0%). A multivariable analysis showed that computed tomography (CT) appearance, tumor location, long axis, and short axis were significantly associated with RLN LN metastasis (all P<0.05). Based on the results of the multivariable analyses, we constructed nomograms that could estimate the probability of RLN LN metastasis. Finally, we stratified the 2 cohorts into risk subgroups using a recursive partitioning analysis (RPA). The risk of left and right RLN LN metastasis was found to be 9.3% and 7.5%, 27.3% and 21.4%, and 52.4% and 47.3% for the low-risk, intermediate-risk, and high-risk groups, respectively. Our nomograms and RPAs appear to be suitable for the risk stratification of left and right RLN LN metastasis in patients undergoing thoracolaparoscopic esophagectomy with cervical anastomosis. This tool could be used to help clinicians to select more effective locoregional treatments, such as surgical protocols and radiation area selection.


Protective role for bcl-2 in experimentally induced cell death of bovine corneal endothelial cells.
To characterize the pattern of cell death and to investigate the potential role of bcl-2 in a death paradigm of corneal endothelial cells, primary cultures of bovine corneal endothelial (BCEN) cells were first established and treated with 0.01-1 microM staurosporine, a nonspecific protein kinase inhibitor. The pattern of BCEN cell death induced by staurosporine was apoptotic in nature, characterized by shrinkage of the cytoplasmic membrane, nuclear condensation and DNA fragmentation. Cotreatment of BCEN cells with Z-VAD-fmk (a caspase inhibitor) but not cycloheximide (a protein synthesis inhibitor) prevented staurosporine-induced cell death. To investigate the potential role of bcl-2, BCEN cells were transferred with a eukaryotic expression vector containing anti-apoptotic bcl-2 cDNA and characterized by reverse transcription-polymerase chain reaction (RT-PCR; BCEN/bcl-2). As measured by the MTT reduction assay after treatment with staurosporine, the survival rate of BCEN/bcl-2 cells was 48.0 +/- 4.8% compared to 7.4 +/- 2.1% in control BCEN cells. As determined by light microscopy, apoptotic changes such as nuclear condensation and apoptotic bodies were largely attenuated in BCEN/bcl-2 cells after staurosporine treatment although arborization of processes and rounding up of the cell body were not affected by overexpression of bcl-2. These results suggest that staurosporine induces apoptosis in a cycloheximide-independent but caspase-dependent manner and bcl-2 acts as a negative regulator in staurosporine-induced apoptosis of BCEN cells.


mTOR-dependent dysregulation of autophagy contributes to the retinal ganglion cell loss in streptozotocin-induced diabetic retinopathy.
Neurodegeneration, an early event in the pathogenesis of diabetic retinopathy (DR), precedes clinically detectable microvascular damage. Autophagy dysregulation is considered a potential cause of neuronal cell loss, however underlying mechanisms remain unclear. The mechanistic target of rapamycin (mTOR) integrates diverse environmental signals to coordinate biological processes, including autophagy. Here, we investigated the role of mTOR signaling in neuronal cell death in DR. Diabetes was induced by a single intraperitoneal injection of streptozotocin and tissue samples were harvested at 1, 2, 3, 4, and 6 months of diabetes. Early-stage of DR was investigated in 1-month-diabetic mice treated with phlorizin (two daily subcutaneous injections at a dose of 200 mg/kg of body weight during the last 7 full days of the experiment and the morning of the 8th day, 3 h before sacrifice) or rapamycin (daily intraperitoneal injections, at a dose of 3 mg/kg for the same period as for phlorizin treatment). The effect of autophagy modulation on retinal ganglion cells was investigated in 3-months-diabetic mice treated with phlorizin (two daily subcutaneous injections during the last 10 full days of the experiment and the morning of the 11th day, 3 h before sacrifice) or MHY1485 (daily i.p. injections, at a dose of 10 mg/kg for the same period as for phlorizin treatment). Tissue samples obtained from treated/untreated diabetic mice and age-matched controls were used for Western blot and histologic analysis. mTOR-related proteins and glucose transporter 1 (GLUT1) was upregulated at 1 month and downregulated in the following period up to 6 months. Diabetes-induced neurodegeneration was characterized by an increase of apoptotic marker-cleaved caspase 3, a decrease of the total number of cells, and NeuN immunoreactivity in the ganglion cell layer, as well as an increase of autophagic protein. Insulin-independent glycemic control restored the mTOR pathway activity and GLUT1 expression, along with a decrease of autophagic and apoptotic proteins in 3-months-diabetic mice neuroretina. However, blockade of autophagy using MHY1485 resulted in a more protective effect on ganglion cells compared with phlorizin treatment. Collectively, our study describes the mechanisms of neurodegeneration through the hyperglycemia/ mTOR/ autophagy/ apoptosis pathway. Video Abstract.


Prenatal exome sequencing and chromosomal microarray analysis in fetal structural anomalies in a highly consanguineous population reveals a propensity of ciliopathy genes causing multisystem phenotypes.
Fetal abnormalities are detected in 3% of all pregnancies and are responsible for approximately 20% of all perinatal deaths. Chromosomal microarray analysis (CMA) and exome sequencing (ES) are widely used in prenatal settings for molecular genetic diagnostics with variable diagnostic yields. In this study, we aimed to determine the diagnostic yield of trio-ES in detecting the cause of fetal abnormalities within a highly consanguineous population. In families with a history of congenital anomalies, a total of 119 fetuses with structural anomalies were recruited and DNA from invasive samples were used together with parental DNA samples for trio-ES and CMA. Data were analysed to determine possible underlying genetic disorders associated with observed fetal phenotypes. The cohort had a known consanguinity of 81%. Trio-ES led to diagnostic molecular genetic findings in 59 fetuses (with pathogenic/likely pathogenic variants) most with multisystem or renal abnormalities. CMA detected chromosomal abnormalities compatible with the fetal phenotype in another 7 cases. Monogenic ciliopathy disorders with an autosomal recessive inheritance were the predominant cause of multisystem fetal anomalies (24/59 cases, 40.7%) with loss of function variants representing the vast majority of molecular genetic abnormalities. Heterozygous de novo pathogenic variants were found in four fetuses. A total of 23 novel variants predicted to be associated with the phenotype were detected. Prenatal trio-ES and CMA detected likely causative molecular genetic defects in a total of 55% of families with fetal anomalies confirming the diagnostic utility of trio-ES and CMA as first-line genetic test in the prenatal diagnosis of multisystem fetal anomalies including ciliopathy syndromes.


Cognition, communication, and hearing in young children with cleft lip and palate and in control children: a longitudinal study.
To compare a group of children with cleft lip and palate (CLP) with a group of noncleft, matched control children on measures of cognitive development, speech and language abilities, and audiologic status at 12 and 24 months of age. Using a prospective, longitudinal study design, a group of 16 children with CLP and a group of 16 noncleft control children matched for race, sex, birth order, and socioeconomic status were compared using the Bayley Scales of Infant Development, the Receptive-Expressive Emergent Language Scale, the Sequenced Inventory of Communication Development-Revised (SICD-R), the Preschool Language Scale-Revised (PLS-R), the mean length of utterance, audiometric evaluation, and impedance screening at 12 and 24 months of age. All were free of other congenital abnormalities or known causes of neurodevelopmental dysfunction. Children with CLP had lower mental developmental index (MDI) and psychomotor developmental index scores than control children. They had lower language comprehension scores on the SICD-R and PLS-R and lower expressive language scores on the Receptive-Expressive Emergent Language Scale, SICD-R, and PLS-R than control children. The group with CLP had a significantly higher number of children with abnormal tympanogram results or ventilation tubes at 12 and 24 months. There was a positive correlation between language test scores at 24 months and MDI scores at 24 months (r = .73 to .85). Seventy-five percent of children with CLP who had hearing loss at 12 months had MDI scores more than 1 SD below the mean versus 0% of children with normal hearing. There was a relationship between hearing status at 12 months and comprehension and expressive language scores at 24 months. Children with CLP had significantly lower scores on tests of cognition, comprehension, and expressive language abilities than matched control children at 12 and 24 months of age. They also had a higher frequency of middle-ear disease and ventilation tubes than control children, although no significant difference in hearing sensitivity was found between groups. Early identification and treatment of these delays may reduce subsequent verbal deficits, hearing loss, and academic difficulties.


Laminectomy alone versus laminectomy with fusion for degenerative cervical myelopathy: a long-term study of a national cohort.
To compare patient-reported 5-year clinical outcomes between laminectomy alone versus laminectomy with instrumented fusion in patients with degenerative cervical myelopathy in a population-based cohort. All patients in the national Swedish Spine Register (Swespine) from January 2006 until March 2019, with degenerative cervical myelopathy, were assessed. Multiple imputation and propensity score matching based on clinicodemographic and radiographic parameters were used to compare patients treated with laminectomy alone with patients treated with laminectomy plus posterior-lateral instrumented fusion. The primary outcome measure was the European Myelopathy Score, a validated patient-reported outcome measure. The scale ranges from 5 to 18, with lower scores reflecting more severe myelopathy. Among 967 eligible patients, 717 (74%) patients were included. Laminectomy alone was performed on 412 patients (mean age 68 years; 149 women [36%]), whereas instrumented fusion was added for 305 patients (mean age 68 years; 119 women [39%]). After imputation, the propensity for smoking, worse myelopathy scores, spondylolisthesis, and kyphosis was slightly higher in the fusion group. After imputation and propensity score matching, there were on average 212 pairs patients with a 5-year follow-up in each group. There were no important differences in patient-reported clinical outcomes between the methods after 5 years. Due to longer hospitalization times and implant-related costs, the mean cost increase per instrumented patient was approximately $4700 US. Instrumented fusions generated higher costs and were not associated with superior long-term clinical outcomes. These findings are based on a national cohort and can thus be regarded as generalizable.


Changes in Free and Conjugated Indole 3-Acetic Acid and Abscisic Acid in Young Cotton Fruits and Their Abscission Zones in Relation to Fruit Retention during and after Moisture Stress.
Experiments were conducted with field-grown cotton (Gossypium hirsutum L.) in 1985 and 1986 to determine effects of water deficit on levels of conjugated indole 3-acetic acid (IAA) and abscisic acid (ABA) in young fruits (bolls) and their abscission zones in relation to boll retention. Tissues were harvested three times during an irrigation cycle in 1985. They were harvested twice during an irrigation cycle and once after irrigation in 1986 to determine extent of recoveries of measured parameters. As reported earlier, the free IAA content of abscission zones decreased with moisture stress. Irrigation caused a partial recovery in free IAA content of abscission zones and caused a partial recovery in rate of boll retention. In contrast to free IAA, conjugated IAA increased with water deficit, both in 3-day-old bolls and in their abscission zones. Bolls contained much more ester IAA than their abscission zones. Some, but not all, of the increase in ester IAA in bolls during moisture stress could have come from a conversion of amide-linked IAA. Amide IAA decreased slightly during stress and increased after irrigation, but the concentration was low relative to ester IAA. Free and conjugated ABA both increased during stress and decreased after irrigation. However, the concentration of conjugated ABA remained relatively high in abscission zones. Ester IAA, being more resistant than free IAA to enzymic destruction during stress, may hasten recovery of fruit retention after relief of stress by providing a source of free IAA in abscission zones to inhibit continued abscission.


A Randomized Controlled Trial Examining the Effects of Mindful Eating and Eating without Distractions on Food Intake over a Three-Day Period.
This study compared the effects of mindful eating and eating without distractions on energy intake and diet over a 3-day period among healthy-weight females. Mindful eating was defined as attending to the sensory properties of one's food as one eats. Participants (n = 99) were asked to either focus on the sensory properties of their food (MIND), eat without distractions (CON-D) or they were not provided with any instructions (CON-I). All participants completed an online food recall measure at the end of each day. Those in the MIND and CON-D groups also rated strategy adherence at the end of each day. Results showed no significant effects of condition on energy intake (ηp2 = 0.00), saturated fat, added sugar and fiber (ηp2 = 0.03), or fruit and vegetables (ηp2 = 0.04). There was also no significant relationship between energy intake and strategy adherence in the MIND group (r = -0.02). For those in the CON-D group, there was a trend toward a negative relationship between energy intake and strategy adherence (r = -0.31, p = 0.085). Among this population, there was no evidence that asking people to attend to the sensory properties of their food improved their diet. Further research is needed to identify mechanisms underpinning significant effects observed in laboratory studies, to help understand when this strategy is, and is not, likely to be helpful.


Executive neurocognitive functioning and neurobehavioral systems indicators in borderline personality disorder: a preliminary study.
It is argued that borderline personality disorder (BPD) represents the interaction of underlying neurobehavioral systems that are reflected principally in the phenotypic constructs of positive emotion, negative emotion, and nonaffective constraint (Depue & Lenzenweger, 2001). This preliminary and exploratory study sought to examine predictions made from the Depue-Lenzenweger model with respect to controlled (effortful) information processing in BPD. It was hypothesized that (a) BPD subjects may display deficits on tasks that require controlled information processing (sustained attention, spatial working memory, and executive functioning), (b) they may reveal elevated negative emotion as well as decreased positive emotion and nonaffective constraint, and (c) nonaffective constraint should be substantially inversely associated with accurate performance on controlled information processing tasks. The results of this study, which examined 24 BPD diagnosed individuals and 68 normal adults, found support for each of these predictions in relation to performance on the Wisconsin Card Sorting Test. The implications of these results for further experimental psychopathology investigations of BPD as well as further refinement of theoretical models of the disorder are discussed.


Amino acid digestibility of different rye genotypes in caecectomised laying hens.
This study investigated the variability of amino acid (AA) digestibility of rye grains in laying hens. Relationships between AA digestibility and physical properties (thousand seed weight, test weight, falling number, and extract viscoelasticity), chemical composition (proximate nutrients, non-starch polysaccharides, AA, minerals, and inositol phosphates), gross energy concentration, and in vitro solubility of nitrogen (N) of the grains were also examined. Twenty rye genotypes were grown under standardised agronomic and environmental conditions as part of a collaborative research project known as "GrainUp". Each genotype was added to a basal diet at 500 g/kg at the expense of maize starch to produce 20 rye diets. The experimental design comprised four Latin Squares (6 × 6) distributed over two runs, resulting in 12 experimental periods. Caecectomised laying hens (LSL-Classic) were individually kept in metabolism cages. Excreta were collected quantitatively for 4 d, and AA digestibility of the rye genotypes was determined using a regression approach. The digestibility of AA was generally low but varied significantly among the 20 rye genotypes, especially for Lys (digestibility range 35-59%), Met (57-75%), Thr (34-54%), and Trp (36-71%). Nevertheless, physical and chemical characteristics as well as the in vitro solubility of N correlated in only a few cases with AA digestibility. Multiple linear regression was used to calculate equations to predict AA digestibility based on the analysed characteristics. However, their explanatory power, as judged by the adjusted R(2), was not sufficiently precise for practical application (below 0.6 for most AA). In conclusion, the AA digestibility of rye grain is generally low and varies significantly between crop genotypes. Equations based on its physical and chemical characteristics are not sufficiently precise to be useful for feed formulation.


Single amino acid substitution in important hemoglobinopathies does not disturb molecular function and biological process.
Hemoglobin is an important protein found in the red cells of many animals. In humans, the hemoglobin is mainly distributed in the red blood cell. Single amino acid substitution is the main pathogenesis of most hemoglobin disorders. Here, the author used a new gene ontology technology to predict the molecular function and biological process of four important hemoglobin disorders with single substitution. The four studied important abnormal hemoglobins (Hb) with single substitution included Hb S, Hb E, Hb C, and Hb J-Baltimore. Using the GoFigure server, the molecular function and biological process in normal and abnormal hemoglobins was predicted. Compared with normal hemoglobin, all studied abnormal hemoglobins had the same function and biological process. This indicated that the overall function of oxygen transportation is not disturbed in the studied hemoglobin disorders. Clinical findings of oxygen depletion in abnormal hemoglobin should therefore be due to the other processes rather than genomics, proteomics, and expression levels.


The multimodal approach to cognitive rehabilitation.
In the past two decades, researchers and practitioners have developed many procedures to improve cognitive functioning. Most of these procedures attempt to produce a change in a client's cognitive processes. For example, clients may be trained in how to pay attention, perceive, rehearse, remember, or think through a problem. Recently, several researchers and practitioners have sought an eclectic approach to treating practical problems of cognition. Clients are not only trained in mental strategies to enhance cognition, they are also equipped with mental prostheses, counseled on how to cope with the stress of cognitive tasks, directed to consume foods and vitamins conducive to good brain chemistry, and taught social skills that augment cognitive performance. This article presents a model that provides a theoretical backdrop for the eclectic approach to cognitive rehabilitation. This approach is rooted in the theoretical assumption that cognitive performance can be influenced by other modes of psychological processing (e.g., physiological, perceptual, emotional, motivational, social, and responses to the physical environment). According to this approach, cognitive rehabilitation achieves the greatest improvement in a client's cognitive functioning (1) by training better thought processes, and (2) by interventions that enhance two or more other modes of processing. The article demonstrates that this multimodal model of cognitive rehabilitation accounts for a wide variety of findings in basic research and clinical research, as well as being consistent with clinical judgment.


Starch degradation in isolated spinach chloroplasts.
A method for loading isolated intact spinach (Spinacia oleracea L.) chloroplasts with (14)C-starch is described. These intact chloroplasts were incubated aerobically in the dark for 30 minutes. Radioactivity in starch declined and glyceric acid 3-phosphate and maltose were the major radioactive products. It is proposed that starch is degraded within the chloroplast to glyceric acid 3-phosphate and to maltose.


Effects of physical randomness training on virtual and laboratory golf putting performance in novices.
External randomness exists in all sports but is perhaps most obvious in golf putting where robotic putters sink only 80% of 5 m putts due to unpredictable ball-green dynamics. The purpose of this study was to test whether physical randomness training can improve putting performance in novices. A virtual random-physics golf-putting game was developed based on controlled ball-roll data. Thirty-two subjects were assigned a unique randomness gain (RG) ranging from 0.1 to 2.0-times real-world randomness. Putter face kinematics were measured in 5 m laboratory putts before and after five days of virtual training. Performance was quantified using putt success rate and "miss-adjustment correlation" (MAC), the correlation between left-right miss magnitude and subsequent right-left kinematic adjustments. Results showed no RG-success correlation (r = -0.066, p = 0.719) but mildly stronger correlations with MAC for face angle (r = -0.168, p = 0.358) and clubhead path (r = -0.302, p = 0.093). The strongest RG-MAC correlation was observed during virtual training (r = -0.692, p < 0.001). These results suggest that subjects quickly adapt to physical randomness in virtual training, and also that this learning may weakly transfer to real golf putting kinematics. Adaptation to external physical randomness during virtual training may therefore help golfers adapt to external randomness in real-world environments.


Thoracic surgery may alter body static balance via diaphragm dysfunction.
Many diseases and conditions can alter an ability to maintain body balance. The aim of the present study was to investigate whether thoracic surgery may elicit diaphragm dysfunction thereby impairing postural stability. 40 patients qualified to video-assisted thoracoscopy (VATS) lobectomy or lobectomy via thoracotomy due to pulmonary carcinoma were examined two times: a day before lung resection and 3-5 days after surgical procedure. Diaphragm assessment was performed using ultrasonography, while postural sways were evaluated by Zebris FDM-S stabilometric platform. Thoracic surgery was associated with decrease of diaphragm thickness and movement, as well as, with deterioration of static body balance maintenance. Upper lobe resection was linked with greater diaphragm excursion restriction and worse body sway parameters than middle and lower lobe resection. VATS lobectomy was associated with better postoperative diaphragm function and better postural sway parameters than lobectomy via thoracotomy. Patients after lobectomy via thoracotomy had significantly more load on lower limb on the operated side than patients after VATS lobectomy. Impairment of diaphragm function is closely associated with equilibrium impairment after pulmonary resection. VATS lobectomy was less invasive than lobectomy via thoracotomy in terms of primary respiratory muscle function and body balance maintenance parameters.


Double Dose Reduction in the Equilibrium Phase of Chest-Pelvic CT With Low Tube Voltage and Forward-Projected Model-Based Iterative Reconstruction Solution.
Objectives This study aimed to examine whether a new imaging method (80-kV forward-projected model-based iterative reconstruction solution [FIRST] protocol) that uses a combination of low tube voltage and FIRST can reduce radiation dose and contrast medium volume by comparing the quality of the resulting image with that of the image obtained by 120-kV adaptive iterative dose reduction 3D protocol in the equilibrium phase of chest-pelvic computed tomography (CT). Subjects and methods Twenty-seven patients underwent CT by both protocols on different days. Two radiologists subjectively assessed image quality by scoring axial images for sharpness, contrast enhancement, noise, artifacts, and overall quality. The mean CT values, standard deviations, contrast-to-noise ratios, and signal-to-noise ratios in the liver, aorta, and erector spinae muscles were used for objective assessment. Radiation dose parameters included the CT dose index volume, dose-length product, effective dose, and size-specific dose estimate. Results were compared for different body mass index categories. Results The 80-kV FIRST protocol helped achieve mean reductions of 36.3%, 35.7%, and 36.6% in CT dose index volume, effective dose, and size-specific dose estimate, respectively (p < 0.01). Therefore, this protocol was regarded as comparable to the conventional protocol in image quality, except for visual sharpness. Conclusions The 80-kV FIRST protocol is capable of reducing radiation dose and contrast medium volume compared to the adaptive iterative dose reduction 3D protocol in the equilibrium phase of chest-pelvic CT.


Shape-controlled synthesis of silver nanostructures.
At room temperature, without any template and in the solid phase, shape-controlled silver nanostructures are synthesized using solid electrolyte RbAg(4)I(5) thin film under direct current electric field (DCEF) treatment. With different DCEF strengths, we have synthesized silver single-crystalline nanowires, nanotubes, nanoparticles and nanoframes. The growth mechanism and the relationship between the DCEF strength and the synthesized nanostructures are discussed briefly.


Inherent bias toward the null hypothesis in conventional multipoint nonparametric linkage analysis.
Traditional nonparametric "multipoint" statistical procedures have been developed for assigning allele-sharing values at a locus of interest to pairs of relatives for linkage studies. These procedures attempt to accommodate a lack of informativity, nongenotyped loci, missing data, and related issues concerning the genetic markers used in a linkage study. However, such procedures often cannot overcome these phenomena in compelling ways and, as a result, assign relevant relative pairs allele-sharing values that are "expected" for those pairs. The practice of assigning expected allele-sharing values to relative pairs in the face of a lack of explicit allele-transmission information can bias traditional nonparametric linkage test statistics toward the null hypothesis of no locus effect. This bias is due to the use of expected values, rather than to a lack of information about actual allele sharing at relevant marker loci. The bias will vary from study to study on the basis of the DNA markers, sample size, relative-pair types, and pedigree structures used, but it can be extremely pronounced and could contribute to a lack of consistent success in the application of traditional nonparametric linkage analyses to complex human traits and diseases. There are several potential ways to overcome this problem, but their foundations deserve greater research. We expose many of the issues concerning allele sharing with data from a large affected-sibling-pair study investigating the genetic basis of autism.


How and why grasshopper community maturation rates are slowing on a North American tall grass prairie.
Invertebrate growth rates have been changing in the Anthropocene. We examine rates of seasonal maturation in a grasshopper community that has been declining annually greater than 2% a year over 34 years. As this grassland has experienced a 1°C increase in temperature, higher plant biomass and lower nutrient densities, the community is maturing more slowly. Community maturation had a nutritional component: declining in years/watersheds with lower plant nitrogen. The effects of fire frequency were consistent with effects of plant nitrogen. Principal components analysis also suggests associated changes in species composition-declines in the densities of grass feeders were associated with declines in community maturation rates. We conclude that slowed maturation rates-a trend counteracted by frequent burning-likely contribute to long-term decline of this dominant herbivore.


House subcommittee rejects effort to remove abortion coverage.
On May 12, (1994) a subcommittee of the House Education and Labor Committee voted 16-11 in support of retaining abortion coverage in the President's proposed health care plan. With its vote, the Labor/Management Relations subcommittee rejected an amendment by Representative Ron Klink (D-PA), which would have allowed insurers to cover abortions only in cases of forcible rape or incest, or life endangerment. Two Republican Representatives joined 14 Democrats voting against the amendment, while 3 Democratic Representatives were among the 11 people supporting the Klink amendment. The subcommittee also defeated an amendment introduced by Representative Dick Armey (R-TX), which would have prohibited any language in a health care reform bill from overruling constitutional state laws restricting abortion. 14 subcommittee members voted against the Armey amendment; 11 voted in favor. The subcommittee is not expected to act on a final health care measure before the Memorial Day recess. In related news, a Veterans' Affairs House subcommittee voted 11-8 on May 11 to prohibit the performance of abortions at Department of Veterans' Affairs Hospitals or the coverage of abortion services by VA funds. The amendment was introduced in the Hospitals and Health Care subcommittee by Representative Chris Smith (R-NJ). Neither subcommittee action represents a final decision on abortion coverage in health care reform and none of the 5 Congressional committees considering health reform is expected to finalize their proposals before the Memorial Day recess. The Senate Labor and Human Resources Committee and the House Ways and Means Committee started work on health care reform on May 18. The Senate Finance Committee has only been meeting privately thus far, while neither the full House Education and Labor Committee nor the House Energy and Commerce Committee has met.


Two years' performance of an in-house ELISA for diagnosis of Legionnaires' disease: detection of specific IgM and IgG antibodies against Legionella pneumophila serogroup 1, 3 and 6 in human serum.
The aim of this study was to evaluate the performance of an in-house ELISA for the diagnosis of Legionnaires' disease (LD) by detection of IgM and IgG antibodies against Legionella (L.) pneumophila serogroups (sg) 1, 3 and 6. The evaluation was done throughout a two-year period in a diagnostic routine laboratory. Furthermore, the sensitivity of four different methods, the in-house L. pneumophila antibody test (ELISA), the urinary antigen test (Binax® EIA), an in-house PCR and culture, both alone and in combination was evaluated. From 2008 to 2010, 12,158 serum samples from 10,503 patients were analysed. During the same period, 361 cases of laboratory-confirmed LD cases were recorded in Denmark, but of these only 113 had a serum sample examined. The positive predictive value of the in-house ELISA was calculated to be 12.8 and the negative predictive value was 99.6, using only the confirmed LD cases as true positives. The sensitivity of the in-house ELISA for the detection of IgM and IgG antibodies in the confirmed LD cases was 61% and 36%, respectively. By combining the two ELISA assays the sensitivity increased to 66%. The sensitivity of the Legionella urinary antigen test (Binax® EIA) was 63%, of the in-house PCR 87% and of culture 69%. When all the different methods were combined, a higher sensitivity was calculated--for in-house ELISA (IgM+IgG) and Binax® EIA 91%, in-house ELISA (IgM+IgG) and in-house PCR 93%, in-house ELISA (IgM+IgG) and culture 93%, Binax® EIA and in-house PCR 79%, Binax® EIA and culture 68% and in-house PCR and culture 94%. This study confirms that the detection of IgG and IgM antibodies by ELISA is an important diagnostic tool, also during the initial phase of the disease. Furthermore, we showed that LD in Denmark with or without serum samples collected exhibits the same age and sex distribution and epidemiology, as in the rest of Europe, i.e., mostly men are infected, infections are mostly community acquired, followed by infection from travelling abroad. Apart from patients with notified LD, the patients investigated by serology were evenly distributed in all age groups; there was only a slightly higher ratio of men tested for "atypical pneumonia" in the serology laboratory.


Functional recovery after traumatic transtentorial herniation.
To elucidate the factors associated with functional recovery after traumatic transtentorial herniation, we reviewed the records of 153 consecutive patients admitted with clinical signs of transtentorial herniation (altered level of consciousness, anisocoria or pupillary unresponsiveness, and abnormal motor findings). Overall, 28 patients (18%) had a functional outcome: 14 patients (9%) made a good recovery and 14 were moderately disabled. Sixteen patients (10.5%) were severely disabled or vegetative, and 104 (60%) died. Compared with patients who died or were left severely disabled or vegetative, patients who had a good recovery were younger (21 versus 38 years), were significantly more likely to be children (less than or equal to 17 years old) and have anisocoria and a deteriorating Glasgow Coma Score (GCS), and were significantly less likely to be flaccid or have bilaterally fixed pupils; moderately disabled patients also had a lower median age and a higher frequency of anisocoria. There was no difference in the incidence of significant intracranial hematomas between patients with a functional outcome and those with a nonfunctional outcome. Twenty-seven percent of the 95 patients with anisocoria had a good outcome or moderate disability, whereas only 3.5% of the 58 patients with bilaterally fixed and dilated pupils at admission had a functional recovery (P less than 0.05). Age, level of consciousness, and the degree of residual upper brain stem function at admission appear to be the most important determinants of functional outcome after traumatic transtentorial herniation.


[Sarcoid optic neuropathy].
Sarcoidosis is a multisystem granulomatous disease mostly involving the chest. Sarcoid optic neuropathy is an uncommon but serious manifestation that requires long-term corticosteroid treatment. We report here the case of a 50-year-old black patient complaining of a recent blurred vision on his left eye. The ophthalmologic examination was normal. Goldmann visual field and visual evoked potentials confirmed the diagnosis of retrobulbar optic neuropathy. Sarcoidosis was presumed on a chest radiography and computed tomography and confirmed with a transbronchial biopsy. Symptoms disappeared with intravenous bolus of corticosteroids. Three months later, without treatment, a right inferior eyelid tumor was observed. Magnetic resonance imaging (RMI) showed two orbital masses and multiple meningeal lesions enhancing with contrast suggesting neurosarcoidosis which decreased with a long-term high-dose corticosteroid therapy (1 mg/kg/d). Optic neuropathy is a rare manifestation of neurosarcoidosis, mostly accompanied by optic-disc involvement with papillary lesions. Chest roentgenogram and computed tomography give a presumption of sarcoidosis. But biopsy is mandatory to confirm the diagnosis demonstrating the histologic lesion of a non caseating granulomatous. Corticosteroid therapy is dramatically efficient but sometimes several months treatment is required.


Oxidative Stress and Cancer Heterogeneity Orchestrate NRF2 Roles Relevant for Therapy Response.
Oxidative stress and its end-products, such as 4-hydroxynonenal (HNE), initiate activation of the Nuclear Factor Erythroid 2-Related Factor 2 (NRF2)/Kelch Like ECH Associated Protein 1 (KEAP1) signaling pathway that plays a crucial role in the maintenance of cellular redox homeostasis. However, an involvement of 4-HNE and NRF2 in processes associated with the initiation of cancer, its progression, and response to therapy includes numerous, highly complex events. They occur through interactions between cancer and stromal cells. These events are dependent on many cell-type specific features. They start with the extent of NRF2 binding to its cytoplasmic repressor, KEAP1, and extend to the permissiveness of chromatin for transcription of Antioxidant Response Element (ARE)-containing genes that are NRF2 targets. This review will explore epigenetic molecular mechanisms of NRF2 transcription through the specific molecular anatomy of its promoter. It will explain the role of NRF2 in cancer stem cells, with respect to cancer therapy resistance. Additionally, it also discusses NRF2 involvement at the cross-roads of communication between tumor associated inflammatory and stromal cells, which is also an important factor involved in the response to therapy.


[Usefulness of immunohistochemistry as a diagnostic tool for tumors and pseudotumoral bone lesions].
Immunohistochemical study for the diagnosis of bone tumors and tumor-like lesions has to be scheduled after an appropriate analysis of clinical data, radiological findings, and results of histology in H-E sections. The value of several markers for osteoblasts is discussed, chiefly for various forms of osteosarcomas. In the same way, the role of S-100 protein as well as anticollagen type II antibody is developed for cartilaginous tumors. The selection of markers in the fields of round cell tumors and spindle cell tumors of bone is also discussed. Some diagnostic problems with the support of immunohistochemistry are described, like chordomas versus chondrosarcomas or bone metastases. Lastly, immunohistochemical study of proliferating factors in the bone tumor field is quoted.


Differential metabolism of neonicotinoids by Myzus persicae CYP6CY3 stably expressed in Drosophila S2 cells.
The peach-potato aphid, Myzus persicae, is a serious crop pest that has developed imidacloprid resistance, mainly through overexpression of CYP6CY3. Here, we established a metabolic assay using Drosophila S2 cells that stably expressed CYP6CY3. We found that CYP6CY3 showed metabolic activity against imidacloprid, as well as acetamiprid, clothianidin, and thiacloprid, but had no activity against dinotefuran. Our study suggested that stable gene expression in Drosophila S2 cells is useful for examining which insecticide is metabolized by P450 monooxygenases.


Retrograde jejunojejunal intussusception status following Roux-en-Y gastrojejunostomy.
Reported herein is an experience with retrograde intussusception. The index case was a 25-year-old African American woman who was status post-multiple previous intraperitoneal procedures, including a truncal vagotomy, distal gastrectomy, and Roux-en-Y gastrojejunostomy for the treatment of gastric outlet obstruction secondary to type 2 peptic ulcer disease. The patient presented most recently with symptoms and signs of a high-grade mechanical intestinal obstruction. Preoperatively, computerized axial tomography revealed retrograde intussusception. Urgent exploratory celiotomy confirmed retrograde intussusception of a segment of the common channel just distal to the jejunojejunostomy. The jejunojejunostomy, including the nonreducible intussusceptum and intussuscipiens, was resected. The alimentary tract was reconstituted in conventional fashion. Light microscopic histopathologic analysis revealed acute greater than chronic inflammation, transmural edema, ischemia/necrosis of the intussusceptum, and hypertrophy of the intussuscipiens. Mechanistically, intussusception has been characterized as an internal prolapse. It usually is aboral/antegrade/isoperistaltic in direction with circumferential intraluminal invagination/prolapse/propagation/telescoping of the proximal/cephalad intussusceptum into the distal/caudad intussuscipiens. Retrograde intussusception is the reverse. More specifically, retrograde intussusception is adoral/retrograde/antiperistaltic in direction with circumferential extraluminal exvagination/propagation/telescoping of the proximal/cephalad intussuscipiens over and around the distal/caudad intussusceptum. We speculate that suture lines, staple lines, adhesive disease, and incomplete closure of mesenteric defects are proximate and determinant causes of retrograde intussusception.


A Study of Electrochemical Sensor Based on BHb-imprinted Magnetic Nanoparticles.
A study of an electrochemical sensor based on bovine hemoglobin (BHb) imprinted magnetic nanoparticles (MIPs) was investigated. First, BHb MIPs were successfully synthesized with magnetic Fe3O4@Au nanoparticles as carrier by surface modification of mercapto propionic acid for introducing carboxyl groups, combined with dopamine as the functional monomer and BHb as the template protein. Then, the MIPs were modified to the surface of a glassy carbon electrode (GCE) for electrochemical analysis by using cyclic voltammetry in the potassium ferricyanide solution. Results show that there was a good dynamic response between electrochemical signals and the adsorption amount of protein in the range of 0.05 to 0.5 mg mL-1. Results show that the sensor exhibits a significant specific recognition toward the template protein via selective test and can be used for analysis of serum samples. The synthesized MIPs are suitable for the removal and enrichment of template protein in proteomics. At the same time, the proposed electrochemical sensor can be used for recognition of BHb.