Salutogenesis: Contextualising place and space in the policies and politics of recovery from drug dependence.
This commentary seeks to make a contribution to applied and academic debates concerning recovery from drug dependence. This involves a discussion of various commonalities relating to the places and spaces of substance use/treatment; the identification of various tensions relating to 'structure and agency' in current service provision and the way in which environmentally disparate settings may be synthesised to establish enabling environments of recovery. At the centre of this discussion is Aaron Antonovsky's (1984) model of 'salutogenesis' (and 'salutogenic environments') and how this conceptual framework may be considered and/or applied in the field of recovery from dependent substance use. Whereas public health, clinical intervention and epidemiology each attempt to identify the underlying causation of illness and ill health, salutogenesis is an agency-led concept that seeks to identify the factors and mechanisms that foster good health and the principles of 'keeping well'. It is suggested that a salutogenic approach to recovery options would draw upon the guiding principles of the framework towards advancing, individual level, recovery capital. These principles being (i) the development of social/cultural capital within socially-constructed environments; in which (ii) individual action (or agency) seeks to (iii) manage ill health; recognise the challenges underlying illness and identify the resources that are available to improve health. The author suggests that opportunities for a more 'salutogenic approach' to recovery may be noted within a grassroots model burgeoning throughout parts of the UK (and known as Recovery Cafés). This design is in stark contrast to the State's more structurally-focused treatment options that may not fully appreciate the influence of agency (and the role of place) in attempts to garner recovery capital. In order to demonstrate the academic and applied value of the proposed salutogenic framework to the issue of recovery from dependence (including the centrality of space and place in debate surrounding substance use/treatment), the author draws upon empirical research as well as theoretical and hypothetical frameworks from the discipline of sociology to illustrate throughout.


Spontaneous translation and language mixing in a polyglot aphasic.
The literature on language mixing in polyglot aphasics is reviewed and a case report of a patient with spontaneous translation is presented. A microgenetic model of language processing provides an interpretive framework for language mixing and spontaneous translation as symptoms of polyglot aphasia. It is suggested that language mixing reflects a deficit at the linguistic level while spontaneous translation reflects a deficit at the prelinguistic level of language processing. A hypothesis about the organization of multiple languages in a single speaker is proposed.


High-purity Isolation for Genotyping Rare Cancer Cells from Blood Using a Microfluidic Chip Cell Sorter.
A multistep sorting method for enrichment of rare cells, such as circulating tumor cells, in the blood without cumbersome pretreatments required by most flow cytometry-based methods, which lead to high cost and decreased detection efficiency, was developed. After only hemolysis and cell staining, cancer cells are enriched by repetitive sorting (3×) based on nuclear-positive, cytokeratin-positive, and CD45-negative expression. Experiments using spikes of PC-9 cells showed a mean recovery of 65% and mean purity of 83%, which was retained up to 72 hours after blood draw using preservative tubes. Significant differences in expression level of programmed death-ligand 1 or vimentin were observed between high- and low-expressing cell lines, concurrently with enrichment. Next-generation sequencing analysis of recovered PC-9, A549, and MDA-MB231 cells successfully detected all known mutations. This novel isolation method applicable for preserved samples with sufficient recovery and purity may be substantially beneficial for recovering cells for subsequent molecular analysis.


Multilayer myocardial strain improves the diagnosis of heart failure with preserved ejection fraction.
The diagnostic and treatment of patients with heart failure with preserved ejection fraction (HFpEF) are both hampered by an incomplete understanding of the pathophysiology of the disease. Novel imaging tools to adequately identify these patients from individuals with a normal cardiac function and respectively patients with HF with reduced EF are warranted. Computing multilayer myocardial strain with feature tracking is a fast and accurate method to assess cardiac deformation. Our purpose was to assess the HFpEF diagnostic ability of multilayer strain parameters and compare their sensitivity and specificity with other established parameters. We included 20 patients with a diagnosis of HFpEF and, respectively, 20 matched controls. We assessed using feature-tracking cardiac magnetic resonance longitudinal and circumferential myocardial strain at three distinct layers of the myocardium: subendocardial (Endo-), mid-myocardial (Myo-), and subepicardial (Epi-). Comparatively, we additionally assessed various others clinical, imaging, and biochemical parameters with a putative role in HFpEF diagnostic: left ventricular end-diastolic volume (LVEDV), left ventricular mass (LVM), interventricular septum (IVS) wall thickness and free wall thickness, left atrial volume and strain, septal and lateral mitral annular early diastolic velocity (e`), E/e´ ratio, and plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP). Global longitudinal strain (GLS) is significantly impaired at Endo (-20.8 ± 4.0 vs. -23.2 ± 3.4, P = 0.046), Myo- (-18.0 ± 3.0 vs. -21.0 ± 2.5, P = 0.002), and Epi- (-12.2 ± 2.0 vs. -16.2 ± 2.5, P < 0.001) levels. Compared with any other imaging parameter, an Epi-GLS lower than 13% shows the highest ability to detect patients with HFpEF [area under the curve (AUC) = 0.90 (0.81-1), P < 0.001] and in tandem with NT-proBNP can diagnose with maximal sensibility (93%) and specificity (100%), patients with HFpEF from normal, composed variable [AUC = 0.98 (0.95-1), P < 0.001]. In a logistic regression model, a composite predictive variable taking into account both GLS Epi and NT-proBNP values in each individual subject reached a sensitivity of 89% and a specificity of 100% with an AUC of 0.98 (0.95-1), P < 0.001, to detect HFpEF. Epi-GLS is a promising new imaging parameter to be considered in the clinical assessment of HFpEF patients. Given its excellent specificity, in tandem with a highly sensitive parameter such as NT-proBNP, Epi-GLS holds the potential to greatly improve the current diagnostic algorithms.


Magnetic resonance imaging guided biopsy of musculoskeletal lesions.
Minimally invasive interventional biopsy procedures have the advantages of accurate localization, small incisions, and rapid recovery. The purpose of this study was to clinically test and evaluate the efficacy of the magnetic resonance imaging (MRI)-guidance techniques for obtaining musculoskeletal biopsies using the appropriate imaging modalities and instruments. We used MRI-compatible biopsy needles from the Invivo Bone Biopsy Set (Daum, Germany), and a 1.5-T closed-magnet MRI scanner was used to perform the MRI-guided biopsy. The pulse sequences included fast spin echo T1- and T2-weighted imaging and gradient echo imaging. The inclusion criteria included the presence of bone or soft tissue masses, infectious disease, and other nonspecific lesions that required tissue confirmation. Lesions that could not be visualized by computed tomography (CT) or other imaging modalities were preferred. From January 2005 through December 2009, 23 patients (12 males and 11 females, aged 11-82 years) underwent musculoskeletal MRI-guided biopsy. The biopsy locations were as follow: spine (n = 12), tibia (n = 3), pelvis (n = 1), femur (n = 2), scapula (n = 1), humerus (n = 1), ulna (n = 1), scapula (n = 1), and soft tissue mass of the shoulder (n = 1). The final diagnoses included bone metastasis (n = 7), spinal osteomyelitis and discitis (n = 5), osteonecrosis after chemotherapy (n = 4), bone marrow change or benign lesion without malignancy (n = 3), insufficiency fracture (n = 1), long bone osteomyelitis (n = 1), soft tissue metastasis (n = 1), and perineural ganglion cyst (n = 1). In 10 of the 23 cases, the lesions were barely visualized or invisible on CT guidance. Pathologic analysis and laboratory culturing revealed that the lesions were successfully accessed by MRI-guided biopsy in 100% (23/23) of cases. No obvious complications developed during or after the procedures. Biopsy under MRI guidance is especially valuable for the localization of bone marrow lesions, viable tumors (after chemotherapy or radiation), and lesions that cannot be visualized using CT. It is both accurate and safe, is a good alternative biopsy method, and may be a good adjunctive technique for the localization of bone lesions for radiofrequency ablation or other interventional procedures.


The role of bicarbonate in the modulation of capacitation, spontaneous acrosome reaction and motility of equine fresh and frozen spermatozoa.
In this study, we defined the composition of the culture medium that yield a significant percentage of alive and functional equine spermatozoa during enough time before artificial insemination. The effects of sodium bicarbonate were analyzed in fresh and frozen semen in respect to sperm viability, capacitation, spontaneous acrosome reaction and several kinetic parameters such as total motility, progressive motility, VCL, VSL, ALH, BCF, LIN. Moreover, employing Bayk-6844 and Nifedipine, the involvement of L-type voltage-gated calcium channels in the modulation of intracellular calcium concentrations was investigated. Results evidenced an immediate effect of sodium bicarbonate in reducing fresh sperm viability and in increasing capacitation and spontaneous acrosome reaction of fresh and frozen spermatozoa. Furthermore, it affected total and progressive motility of fresh and frozen semen. Because of the sudden effects of the compound, we think that a buffer lacking sodium bicarbonate is more suitable to preserve the viability and the functional state of equine spermatozoa required to undergo at the right time those modifications necessary for fertilization. We also demonstrated that intracellular calcium modifications induced by Bayk-8644 and Nifedipine are not involved in signals related to vitality, capacitation, spontaneous acrosome reaction and motility.


Methodological and institutional considerations for the use of 360-degree video and pet animals in human subject research: An experimental case study from the United States.
Head-mounted virtual-reality headsets and virtual-reality content have experienced large technological advances and rapid proliferation over the last years. These immersive technologies bear great potential for the facilitation of the study of human decision-making and behavior in safe, perceptually realistic virtual environments. Best practices and guidelines for the effective and efficient use of 360-degree video in experimental research is also evolving. In this paper, we summarize our research group's experiences with a sizable experimental case study on virtual-reality technology, 360-degree video, pet animals, and human participants. Specifically, we discuss the institutional, methodological, and technological challenges encountered during the implementation of our 18-month-long research project on human emotional response to short-duration 360-degree videos of human-pet interactions. Our objective in this paper is to contribute to the growing body of research on 360-degree video and to lower barriers related to the conceptualization and practice of research at the intersection of virtual-reality experiences, 360-degree video, live animals, and human behavior. Practical suggestions for human-subject researchers interested in utilizing virtual-reality technology, 360-degree videos, and pet animals as a part of their research are discussed.


Covid-19 responsible for acute limb ischemia twice at 2 different stages in a patient on anticoagulation: A case report.
Coronavirus disease-2019 is a worldwilde pandemic not limited to pulmonary dysfunction. it is a systemic infection responsible for serious coagulopathies. We report the case of a patient who presented an acute ischemia of the left lower limb, after day 5 of (Covid-19) infection, with a second thrombotic localization in the left upper limb at the twentieth day of post covid while he was on anticoagulation. Several studies have shown the involvement of the inflammatory process in the thrombotic state in patients with (Covid-19) infection. The inflammatory process leads to the activation of the thrombotic cascade. Various elevated markers have been identified frequently and described to determine the progression of sepsis-induced prothrombotic disease secondary to Covid-19. Our case remains unique in its kind, since the patient presented twice the acute ischemia of the limbs, the first at the left lower limb, while he was on preventive low molecular weight heparin (LMWH), the second time at the left upper limb, while he was on anticoagulation (RIVAROXABAN 20 mg/jr). Although the efficiency of preventive anticoagulation in Covid-19 patients has not been established, it remains systematic as a prescription in the hospital environment. All in all, The regular monitoring of vascular markers thrombosis, and preventive anticoagulation remains the only weapon available to any clinician to fight against vascular thrombotic complications in Covid-19 patients, though its realiability has not been proven.


Paternal origin of trisomy 21 following intracytoplasmic sperm injection (ICSI).
One important aspect in the debate on the genetic risks associated with intracytoplasmic sperm injection (ICSI) is the possible increased rate of chromosomal abnormalities in resulting pregnancies. ICSI was performed in a 27 year old man with asthenoteratozoospermia and his 25 year old wife. There was a spontaneous miscarriage at 9 weeks of gestation. Cytogenetic investigation revealed trisomy 21. Analysis of two polymorphic microsatellite markers showed that the additional chromosome was paternal. This is in contrast to the fact that the vast majority of trisomic concepti are maternal in origin. Identifying the parent of origin in trisomic conceptions achieved by ICSI may reveal whether ICSI is associated with an increased risk of paternally derived aneuploidy.


[Biomechanic shear stress in carotid arteries and atherosclerosis development].
One of the major hemodynamic forces acting on blood vessels is shear stress, which is, the friction force between the endothelial cell surface and flowing blood. Arterial shear stress within physiologic range (15-70 dyne/cm2) induces endothelial quiescence and an atheroprotective gene expression profile. Low shear stress (< 4 dyne/cm2) stimulates atherogenic phenotype, whereas, high shear stress (> 70 dyne/cm2) induce prothrombotic state.


[Vibration and noise control in working areas using a restrained-layer dampening system].
Propagation principles of vibrations from machines and possible damages to operators are described. The author points out how to limit and avoid any possible harm. The restrained layer damping system is taken into account, its advantages and peculiarities are examined in particular.


B-mode ultrasound measurement of carotid bifurcation stenoses: is it reliable?
In the majority of cases, duplex ultrasonography (DU) is the sole imaging study necessary before carotid interventions. Duplex-derived internal carotid artery (ICA) peak systolic velocity (PSV), ICA end-diastolic velocity (EDV) and ICA/common carotid artery (CCA) PSV ratio are the most commonly utilized parameters for predicting critical carotid stenoses. However, the role of direct B-mode image measurement of maximal ICA narrowing is ill defined. The images and records of 192 patients who underwent both arteriography and duplex ultrasonography (DU) of 375 carotid arteries from January 1995 to November 2000 were reviewed. All DUs were performed by registered vascular technologists (n=6). Maximum arteriographic stenosis was determined according to the NASCET study design. With arteriography as the "gold standard," B-mode image (BMI) measurement of the maximal ICA luminal narrowing relative to the carotid bulb (n=162)as well as the peak systolic velocity in the internal carotid artery (PSVICA) (n=330), end-diastolic velocity in the internal carotid artery (EDV(ICA)) (n=198), and the ratio of the PSVs in both the ICA and the CCA (PSVICA/CCA) ratio (n=319) were subjected to receiver operator characteristics (ROC) curves for 3 clinically relevant stenoses thresholds: 50-99%, 60-99%, and 70-99%. A strong correlation was found between B-mode image (BMI)and the NASCET arteriographic measures of carotid stenosis (r =0.80;p<0.001) and was similar among the 6 technologists (r =0.74-0.89;p>0.2). The overall accuracy of BMI measurement to diagnose 50%, 60%,and 70% arteriographic carotid stenosis was 85.3%, 82.2%, and 87%, respectively. BMI measurement was similar to the most accurate PSV(ICA), EDV(ICA), and PSV(ICA/CCA) ratio at all 3 threshold stenoses levels (p>0.3). When combined with the velocity criteria, BMI measurement improved the positive predictive value (PPV) for all arteriographic stenoses thresholds by an average of 12.6% for PSV(ICA), 21.2% for EDV(ICA), and 14.2% for PSV(ICA/CCA) ratio. BMI measurement of carotid bifurcation narrowing is as reliable as duplex-derived velocity criteria in evaluating clinically relevant threshold ICA stenoses. The routine use of B-mode ultrasound in conjunction with the velocity parameters enhances the PPV of carotid DU. Our experience suggests that with current refinements in B-mode resolution, BMI stenosis measurements are accurate among experienced technologists and are a useful adjunct to duplex-derived velocity parameters.


Cross-format physical similarity effects and their implications for the numerical cognition architecture.
The sound |faɪv| is visually depicted as a written number word "five" and as an Arabic digit "5." Here, we present four experiments--two quantity same/different experiments and two magnitude comparison experiments--that assess whether auditory number words (|faɪv|), written number words ("five"), and Arabic digits ("5") directly activate one another and/or their associated quantity. The quantity same/different experiments reveal that the auditory number words, written number words, and Arabic digits directly activate one another without activating their associated quantity. That is, there are cross-format physical similarity effects but no numerical distance effects. The cross-format magnitude comparison experiments reveal significant effects of both physical similarity and numerical distance. We discuss these results in relation to the architecture of numerical cognition.


Prolonged latencies of the N2 and P3 of the auditory event-related potential in children at risk for schizophrenia. A preliminary report.
In previous studies investigating long latency components of the event-related potential (ERP), schizophrenic patients generally showed reduced P3 amplitudes and in some studies prolonged N2 or P3 latencies. As there is a higher risk of offspring of schizophrenics than of mentally healthy parents developing this disease, the present study was intended to clarify whether ERP components (in particular the N2 and P3) differ between these two groups of children. Twelve high-risk and 12 age-matched control children (aged 9-16 years) performed an auditory oddball task in order to assess late ERP components. This task required the subject to covertly count rare target tone pips (P = 0.2) irregularly interspersed among frequent standard tone pips (P = 0.8) in two series of 400 pips. ERPs were recorded from midline electrodes (Fz, Cz, Pz). The results indicated distinctly prolonged N2 and P3 latencies in ERPs to target stimuli in children of schizophrenic patients. These findings suggest a slowed target classification in these children.


The influence of primary and subsequent limb amputation on the overall rate of limb amputation in Saskatchewan, Canada, 2006-2019: a population-based study.
Understanding trends in limb amputation (LA) can provide insight into the prevention and optimization of health care delivery. We examine the influence of primary (first report) and subsequent (multiple reports) limb amputation on the overall (all reports) rate of limb amputation in Saskatchewan considering amputation level. Hospital discharged data associated with LA from 2006 to 2019 and population estimates in Saskatchewan were used. LA cases were grouped based on overall, primary, and subsequent LA and further divided by level into major (through/above the ankle/wrist) and minor (below the ankle/wrist). Incidence rates were calculated using LA cases as the numerator and resident population as the denominator. Joinpoint and negative binomial were used to analyze the trends. In addition, the top three amputation predisposing factors (APF) were described by LA groups. The rate of overall LA and primary LA remained stable (AAPC - 0.9 [95% CI - 3.9 to 2.3]) and (AAPC -1.9 [95% CI -4.2 to 0.4]) respectively, while the rate of subsequent LA increased 3.2% (AAPC 3.2 [95% CI 3.1 to 9.9]) over the 14-year study period. The rate of overall major LA declined 4.6% (AAPC - 4.6 [95% CI -7.3 to -1.7]) and was largely driven by the 5.9% decline in the rate of primary major LA (AAPC - 5.9 [95% CI - 11.3 to -0.2]). Subsequent major LA remained stable over the study period (AAPC -0.4 [95% CI - 6.8 to 6.5]). In contrast, the overall rate of minor LA increased 2.0% (AAPC 2.0 [95% CI 1.0 to 2.9]) over the study period which was largely driven by a 9.6% increase in the rate of subsequent minor LA (AAPC 9.6 [95% CI 4.9 to 14.4]). Primary minor LA rates remained stable over the study period (AAPC 0.6 [95% CI - 0.2 to 1.5]). The study cohorts were 1.3-fold greater risk of minor LA than major LA. Diabetes mellitus (DM) was the leading APF representing 72.8% of the cohort followed by peripheral vascular disease (PVD) and trauma with 17.1 and 10.1% respectively. Most (86.7%) of subsequent LA were performed on people with DM. Overall LA rates remained stable over the study period with declining rates of major LA countered by rising rates of minor LA. Minor LA exceeded major LA with the largest rate increase identified in subsequent minor LA. Diabetes was the greatest APF for all LA groups. This rising rate of more frequent and repeated minor LA may reflect changing intervention strategies implemented to maintain limb function. The importance of long-term surveillance to understand rates of major and minor LA considering primary and subsequent intervention is an important step to evaluate and initiate prevention and limb loss management programs.


Dual regulatory effect of plant extracts of Forsythia suspense on RANTES and MCP-1 secretion in influenza A virus-infected human bronchial epithelial cells.
In this study, we investigated the effects of 95% ethanol (FS-t1), 50% ethanol (FS-t2) and water (FS-w) extracts of Forsythia suspense Vahl (Oleaceae) on the production of regulated on activation, normal T cell expressed and secreted (RANTES) and macrophage chemotactic protein-1 (MCP-1) by influenza A virus (H1N1)-infected human bronchial epithelial cell line A549. Virus infection evoked a markedly enhanced production of RANTES from basal 16 +/- 4 to 1307 +/- 294 pg/ml after 72 h inoculation. At the non-cytotoxic doses (20, 100 and 200 microg/ml), FS-t1, FS-t2 and FS-w exhibited a consistent inhibitory effect on virus-stimulated RANTES secretion in a dose-dependent manner wilh IC(50) of 42 +/- 6, 117 +/- 15 and 232 +/- 28 microg/ml, respectively. H1N1 also stimulated MCP-1 production in A549 cells, however to a less degree, from basal 133 +/- 21 to 391 +/- 98 pg/ml after 72 h viral inoculation. The effects of three extracts on MCP-1 secretion were more complex. FS-t1 displayed both positive and negative effect on virus-stimulated MCP-1 production dependent on the concentrations used. On the other hand, FS-t2 increased virus-induced MCP-1 secretion by 1.4-3.3 times while the third fraction FO-w increased by 2.6-3.7 times. These results suggested that Forsythia suspense consisted of both negative and positive regulatory components on RANTES and MCP-1 secretion in H1N1-infected A549 cells, respectively.


Mapping of sensory-responsive cells in the septal area of the rat.
A study of sensory-responsive characteristics of single cells of the septal area of male rats was undertaken to determine the distribution of stimulation-induced changes in septal activity. Single cells were systematically sampled in six planes transecting the rostral-caudal axis of the septal area and were tested for responsiveness to visual, auditory, tactual, gustatory and olfactory stimuli. Approximately 50% of the sampled population of septal cells was responsive to at least one stimulus. Most of the responses of septal cells to stimulation were excitatory and occurred at the onset of stimulation. Regions of concentration of sensory-responsiveness cells in the system were found to lie in medial areas of the septum consisting of the dorsomedial portion of the lateral septal nucleus, the medial septal nucleus and the ventral portions of the medial and lateral nuclei. Visual, auditory and tactual stimuli were most effective in producing changes in spontaneous activity of units in these regions. On the basis of relationships of the medial septal region to other limbic areas having sensory-responsive properties, it is concluded that the medial septal area is one component of a limbic sensory system.


Protein-drug nanoconjugates: Finding the alternative proteins as drug carrier.
Present study was conducted to establish the interaction of bovine fetuin-A to validate its binding modalities with doxorubicin (Dox). Fetuin-A was purified to highest purity and monodispersity. Green synthesis of fetuin-A conjugated gold nanoparticles (F-GNPs) has been performed giving typical UV-maxima with subtle variation in fourier transform infrared spectroscopy (FTIR). Atomic force microscopy (AFM) revealed spherical shaped, polydisperse F-GNPs of varying sizes, complementing the radius of hydration (19.5-62.4nm) by dynamic light scattering (DLS). Circular dichroism (CD) analysis of fetuin-A with respect to Dox interaction shows remarkable reduction in ellipticity with increasing concentrations of Dox (20-120μM). Fetuin-A:Dox and F-GNPs:Dox at variable concentrations revealed significantly enhanced absorption spectra, while a continuous decrease in florescence (560nm). This effect was more drastic when Dox interact with fetuin-A as compared to F-GNPs. Some known antimicrobial drugs were also investigated under similar conditions, giving strong quenching effect in a dose dependent manner suggesting the significant yet differential interactions. In cytotoxicity assay, fetuin-A:Dox conjugates revealed less toxicity as compared to F-GNPs:Dox and Dox alone. In-silico studies of the fetuin-A:Dox complex suggest that the drug binds in the major grove between beta-sheet and long loop region of D1 domain and stabilized by several hydrogen bonds.


An approach for the in vitro screening of drugs for activity against leprosy.
Slow growing strains of mycobacteria isolated from leprous tissues present a characteristic resistance pattern to antibacterial agents that is comparable to drug sensitivity of M. leprae in man.


Influence of practice on response-selection and response-implementation processes involved in the response-interference effect.
In a choice reaction-time task, the response-interference effect is an increase in reaction times when the two possible responses are from the same hand compared to when the two possible responses are from different hands [Psychonomic Science 2 (1965) 55-56; Human Motor Control, Academic Press, San Diego, CA, 1991]. Although the influence of practice on other reaction-time effects (i.e., the complexity effect and precuing) has been examined, research evaluating the influence of practice on the response-interference effect is limited. Therefore, two experiments were conducted to determine the influence of practice on the response-interference effect. In Experiment 1, a bilateral transfer task was used to assess the influence of practice on the response-selection processes associated with the response-interference effect. The practice results indicated decreased reaction times, but did not influence the response-interference effect. In Experiment 2, a priming task was used to assess the influence of practice on response-implementation processes associated with the response-interference effect. The reaction time results indicated a change in the response-interference effect. The results of these two experiments suggest that with only two fingers on response keys, practice alters the mechanical constraints affecting the response-implementation processes and thereby decreases the response-interference effect.


Physiological mass measurements on Skylab 1/2 and 1/3.
Mass measurements of crewmen and objects were made for the first time in space during Skylab. A description of the new devices designed for such measurements and of the technique of their use is detailed. Results from ground-based chamber simulation tests and from those during Skylab II and III show similar patterns of simple metabolic deficits, of a rapid loss during the first few days of flight followed by a reciprocal gain for the first few postflight days, and other transient changes. It is concluded that two major causes of weight loss are present: (1) a fluid redistribution and loss, and (2) metabolic losses. Added to these are short-term changes from transient stress. Smaller, simpler, and cheaper devices have since been designed which should allow mass measurements on virtually any object in almost any spacecraft.


Drug interaction databases in medical literature: transparency of ownership, funding, classification algorithms, level of documentation, and staff qualifications. A systematic review.
It is well documented that drug-drug interaction databases (DIDs) differ substantially with respect to classification of drug-drug interactions (DDIs). The aim of this study was to study online available transparency of ownership, funding, information, classifications, staff training, and underlying documentation of the five most commonly used open access English language-based online DIDs and the three most commonly used subscription English language-based online DIDs in the literature. We conducted a systematic literature search to identify the five most commonly used open access and the three most commonly used subscription DIDs in the medical literature. The following parameters were assessed for each of the databases: Ownership, classification of interactions, primary information sources, and staff qualification. We compared the overall proportion of yes/no answers from open access databases and subscription databases by Fisher's exact test-both prior to and after requesting missing information. Among open access DIDs, 20/60 items could be verified from the webpage directly compared to 24/36 for the subscription DIDs (p = 0.0028). Following personal request, these numbers rose to 22/60 and 30/36, respectively (p < 0.0001). For items within the "classification of interaction" domain, proportions were 3/25 versus 11/15 available from the webpage (P = 0.0001) and 3/25 versus 15/15 (p < 0.0001) available upon personal request. Available information on online available transparency of ownership, funding, information, classifications, staff training, and underlying documentation varies substantially among various DIDs. Open access DIDs had a statistically lower score on parameters assessed.


Zosteriform metastasis: case presentation and review of the literature.
In contrast to benign tumors, malignant tumors, by definition, are characterized by the potential of giving rise to metastases. Albeit infrequently, skin metastases do occur, and their clinical appearance varies over a wide morphologic spectrum. We present the case of a 65-year-old male with zosteriform metastasis secondary to bronchogenic adenocarcinoma. A review of cutaneous metastasis is presented with emphasis on dermatomal distribution and possible mechanisms of dissemination.


Development of the human aortic arch system captured in an interactive three-dimensional reference model.
Variations and mutations in the human genome, such as 22q11.2 microdeletion, can increase the risk for congenital defects, including aortic arch malformations. Animal models are increasingly expanding our molecular and genetic insights into aortic arch development. However, in order to justify animal-to-human extrapolations, a human morphological, and molecular reference model would be of great value, but is currently lacking. Here, we present interactive three-dimensional reconstructions of the developing human aortic arch system, supplemented with the protein distribution of developmental markers for patterning and growth, including T-box transcription factor TBX1, a major candidate for the phenotypes found in patients with the 22q11.2 microdeletion. These reconstructions and expression data facilitate unbiased interpretations, and reveal previously unappreciated aspects of human aortic arch development. Based on our reconstructions and on reported congenital anomalies of the pulmonary trunk and tributaries, we postulate that the pulmonary arteries originate from the aortic sac, rather than from the sixth pharyngeal arch arteries. Similar to mouse, TBX1 is expressed in pharyngeal mesenchyme and epithelia. The endothelium of the pharyngeal arch arteries is largely negative for TBX1 and family member TBX2 but expresses neural crest marker AP2α, which gradually decreases with ongoing development of vascular smooth muscle. At early stages, the pharyngeal arch arteries, aortic sac, and the dorsal aortae in particular were largely negative for proliferation marker Ki67, potentially an important parameter during aortic arch system remodeling. Together, our data support current animal-to-human extrapolations and future genetic and molecular analyses using animal models of congenital heart disease. © 2013 Wiley Periodicals, Inc.


Interaction of dicaffeoylquinic derivatives with peroxynitrite and other reactive nitrogen species.
Plant phenolic antioxidants, among them catechins and hydroxycinnamoyl conjugates, constitute a well defined class of inhibitors of reactive nitrogen species (RNS). To gain deeper insight in this field, we examined the effects of 3,5-di-O-caffeoylquinic acid (DCA), its methyl ester (DCE) and epigallocatechin gallate (EGCG) in nitrative and oxidative processes. These compounds were found to be strong inhibitors of the nitration of tyrosine residues induced by ONOO- in bovine seroalbumin, with their IC50 values (10-40 microM) notably decreasing in the presence of bicarbonate. When studied on the intracellular protein tyrosine nitration induced by ONOO- in cultured murine fibroblasts as well as that induced by phorbol ester (PMA) in nitrite-supplemented human neutrophils, all three phenolics were also effective (100% and over 75% inhibition for fibroblasts and neutrophils, respectively, at 25 microM). This ability seems to be due to a direct interaction with ONOO- or with the species generated by leukocytes. The possible interference with the production of NO was also studied: both DCA and EGCG inhibited nitrite production in LPS-stimulated macrophages by 24% and 40%, respectively, and the expression of nitric oxide synthase-2 (NOS-2), as well. DCA and EGCG reduced by 52% and 59%, respectively, the NF-kappaB transcriptional activity. In contrast, DCE did not show any effect. The assayed phenolics exert varying degrees of protection against the chemical modifications induced by RNS depending not only on the hydroxyl pattern, but also on the presence of bicarbonate.


Vesicovaginal Fistula in Adolescent Girls: Incidence and Management.
The purpose of the study was to analyze the incidence, causes, and management of vesicovaginal fistula (VVF) in adolescent girls. Three girls of adolescent age were diagnosed with VVF, caused by a vaginal foreign body (ie, an aerosol spray cap). Transvesical reconstruction was performed in 2 cases. After the diagnosis of VVF, the third girl was discharged home with Foley catheter drainage. Three months later, she presented with pregnancy and was lost to follow-up. Evaluation of unusual urinary symptoms in an adolescent should include vaginal examination and/or imaging. Aerosol spray caps remain the most common vaginal foreign body resulting in VVFs in adolescent girls in Lithuania. Transvesical reconstruction is safe and efficient.


Enantioselective drug monitoring of (R)- and (S)- propranolol in human plasma via derivatization with optically active (R,R)-O,O-diacetyl tartaric acid anhydride.
A sensitive high-performance liquid chromatographic method was developed for the stereoselective assay of (R)- and (S)-propranolol in human plasma. The method involves diethyl ether extraction of the drugs and a racemic internal standard, N-tert.-butylpropranolol, followed by derivatization of the compounds with the chiral reagent (R,R)-O,O-diacetyl tartaric acid anhydride. The resulting diastereomeric derivatives were separated isocratically on a reversed-phase column. Quantitation was achieved by the peak-height ratio method with reference to the internal standard. The assay was accurate and reproducible in the concentration range 1-100 ng of (R)- and (S)-propranolol per ml plasma, using fluorescence detection at lambda ex 290 nm and lambda em 335 nm. The applicability of this method was demonstrated for the determination of concentration-time profiles of propranolol enantiomers in the course of comparative pharmacokinetic studies.


Biochemical and ultrastructural changes in Staphylococcus aureus treated with staphylococcin 1580.
Incorporation of precursors into macromolecules is immediately arrested upon treatment of Staphylococcus aureus cells with staphylococcin 1580. Except for a degradation of RNA, induced after about 40 min, no degradation of macromolecules is observed, and no trichloroacetic acid-insoluble components are released from the cells. The protein composition and content of membranes are not affected by staphylococcin 1580 treatment. The fatty acid pattern of cells is not significantly altered. Protoplasts do not lyse apparently upon treatment with staphylococcin 1580, but undergo morphological alterations. Thin sections of cells treated with the bacteriocin for 30 min show extensive mesosome-like structures, mostly arranged in honeycomb arrays connected to the plasma membrane, and alterations in the nucleoid area. Freeze-etched preparations taken after that time reveal alterations in the plasma membrane, presumably in relation to the formation of the mesosomal structures. No alterations were observed after bacteriocin treatment for 5 min, although at that time the permeability of the membrane is strongly affected. The implications of the observed changes with the development of irreversible lesions in the cells are discussed.


Influence of positive lymphocyte crossmatch and HLA mismatching on vanishing bile duct syndrome in human liver allografts.
Among the first 52 recipients of primary liver allografts with follow-up of 2 weeks or greater, 6 patients had biopsy-confirmed vanishing bile duct syndrome (VBDS) and required retransplantation. Five of these six patients had positive lymphocyte crossmatches. Of the 46 remaining liver transplant recipients, 11 had positive crossmatches. Thus, the incidence of VBDS was 5/16 in recipients with a positive crossmatch and 1/36 in recipients with a negative crossmatch. The positive-crossmatch group was significantly more likely to develop VBDS than the negative-crossmatch group (P less than 0.004, log rank test). Additional HLA studies comparing degree of donor-recipient mismatch at the various HLA loci showed no significant difference between the groups for class I disparity. However, class II mismatch was of borderline significance (P less than 0.056). When evaluated individually, the DQ mismatch (P less than 0.04) appeared to be more important than the DR mismatch (P = NS). Our data suggest that a positive lymphocyte crossmatch and a class II mismatch, in particular HLA DQ disparity, may play an important role in the pathogenesis of VBDS.


The role of parenting practices in parent and child mental health over time.
Parent and child mental health has suffered during the pandemic and transition phase. Structured and shared parenting may be intervention targets beneficial to families who are struggling with parent or child mental health challenges. First, we investigated associations between structured and shared parenting and parent depression symptoms. Second, we investigated associations between structured and shared parenting and depression, hyperactivity/inattention and irritability symptoms in children. A total of 1027 parents in two-parent households (4797 observations total; 85.1% mothers) completed online surveys about themselves and their children (aged 2-18 years) from April 2020 to July 2022. Structured parenting and shared parenting responsibilities were assessed from April 2020 to November 2021. Symptoms of parent depression, child depression, child hyperactivity and inattention, child irritability, and child emotional and conduct problems were assessed repeatedly (one to 14 times; median of four times) from April 2020 to July 2022. Parents who reported higher levels of shared parenting responsibilities had lower depression symptoms (β = -0.09 to -0.32, all P < 0.01) longitudinally. Parents who reported higher levels of shared parenting responsibilities had children with fewer emotional problems (ages 2-5 years; β = -0.07, P < 0.05), fewer conduct problems (ages 2-5 years; β = -0.09, P < 0.01) and less irritability (ages 13-18 years; β = -0.27, P < 0.001) longitudinally. Structured parenting was associated with fewer conduct problems (ages 2-5 years; β = -0.05, P < 0.05). Shared parenting is beneficial for parent and child mental health, even under chaotic or inflexible life conditions. Structured parenting is beneficial for younger children.


Incidental appendectomy? Microscopy tells another story: A retrospective cohort study in patients presenting acute right lower quadrant abdominal pain.
Optimal management of macroscopically normal appendix encountered during laparoscopy for acute abdominal pain is still unclear. 164 acute abdominal pain cases in which laparoscopy showed a normal appendix were reviewed. No other intra-peritoneal acute disease was present in 50 patients (Group 1) whereas a miscellanea of intra-peritoneal conditions was identified in the other 114 (Group 2). All the patients underwent appendectomy with specimen examination. Following incidental appendectomy significant microscopical changes were seen in 125 specimens (76%). Among these, inflammation was found in 122 and neuroendocrine tumors in 3. Appendices harbored pathological changes in n = 45 patients (90%) of Group 1 and in n = 34 patients (70%) of Group 2 patients (p < 0.05). Morbidity for incidental appendectomy was 2%. This study supports an appendectomy in patients who are undergoing laparoscopy for acute right lower quadrant abdominal pain even when the appendix appears normal on visual inspection.


Technical Video: Bilateral Tubal Adhesiolysis With Cuff Salpingostomy.
To show the steps involved in a bilateral tubal adhesiolysis and cuff salpingostomy. Technical video showing tubal adhesiolysis and cuff salpingostomy in a step-by-step approach. Minimal Access Therapy Training Unit, Royal Surrey County Hospital, Guildford, UK, a tertiary referral unit for complex gynecologic endoscopic surgery. A 38-year-old woman presented with left-sided pelvic pain and primary infertility for 13 years. An ultrasound scan showed bilateral hydrosalpinges with suspected adnexal adhesions. Hysterosalpingography did not show spill of dye. After counseling, she opted to have tubal adhesiolysis and bilateral cuff salpingostomy. Tubal surgery for occlusion has become less popular because of the superior success rates of assisted reproductive techniques. As a result, tubal surgery may eventually become a historic operation. However, in cases of distal tubal blockage after adhesionlysis and cuff salpingostomy or neosalpingostomy, pregnancy rates up to 35% have been reported in the literature. Furthermore, performing a bilateral salpingectomy instead in these cases renders a patient entirely dependent on assisted reproductive techniques for tubal factor infertility. Therefore, a bilateral cuff salpingostomy should be considered in a select group of patients.


Haloperidol prophylaxis for elderly hip-surgery patients at risk for delirium: a randomized placebo-controlled study.
To study the effectiveness of haloperidol prophylaxis on incidence, severity, and duration of postoperative delirium in elderly hip-surgery patients at risk for delirium. Randomized, double-blind, placebo-controlled trial. Large medical school-affiliated general hospital in Alkmaar, The Netherlands. A total of 430 hip-surgery patients aged 70 and older at risk for postoperative delirium. Haloperidol 1.5 mg/d or placebo was started preoperatively and continued for up to 3 days postoperatively. Proactive geriatric consultation was provided for all randomized patients. The primary outcome was the incidence of postoperative delirium (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and Confusion Assessment Method criteria). Secondary outcomes were the severity of delirium (Delirium Rating Scale, revised version-98 (DRS-R-98)), the duration of delirium, and the length of hospital stay. The overall incidence of postoperative delirium was 15.8%. The percentage of patients with postoperative delirium in the haloperidol and placebo treatment condition was 15.1% and 16.5%, respectively (relative risk=0.91, 95% confidence interval (CI)=0.6-1.3); the mean highest DRS-R-98 score+/-standard deviation was 14.4+/-3.4 and 18.4+/-4.3, respectively (mean difference 4.0, 95% CI=2.0-5.8; P<.001); delirium duration was 5.4 versus 11.8 days, respectively (mean difference 6.4 days, 95% CI=4.0-8.0; P<.001); and the mean number of days in the hospital was 17.1+/-11.1 and 22.6+/-16.7, respectively (mean difference 5.5 days, 95% CI=1.4-2.3; P<.001). No haloperidol-related side effects were noted. Low-dose haloperidol prophylactic treatment demonstrated no efficacy in reducing the incidence of postoperative delirium. It did have a positive effect on the severity and duration of delirium. Moreover, haloperidol reduced the number of days patients stayed in the hospital, and the therapy was well tolerated.


Increased short interval intracortical inhibition in participants with previous hamstring strain injury.
Cortical mechanisms may contribute to weakness in participants with previous hamstring strain injury. This study aims to examine intra-cortical inhibition (SICI) and corticospinal excitability in previously injured participants. In this cross-sectional study, TMS was used to examine SICI, silent period, silent period: MEP ratios and area under the stimulus response curve in the biceps femoris and medial hamstrings. Comparisons were made between participants with (n = 10) and without (n = 10) previous hamstring strain injury. Motor threshold and isometric knee flexor strength were also compared between participants and the relationship between strength and SICI in control and previously injured participants was examined. Isometric knee flexor strength was lower in previously injured limbs compared with control limbs (mean difference = - 41 Nm (- 26%) [95% CI = - 80 to - 2 Nm], p = 0.04, Cohen's d = - 1.27) and contralateral uninjured limbs (mean difference = - 23 Nm (- 17%), [95% CI = - 40 to - 6 Nm], p = 0.01, Cohen's d = - 0.57). Previously injured limbs exhibited smaller responses to paired pulse stimulation (i.e. greater levels of SICI) in the biceps femoris compared with control limbs (mean difference = - 19%, [95% CI = - 34 to - 5%], p = 0.007, Cohen's d = - 1.33). Isometric knee flexor strength was associated with the level of SICI recorded in the biceps femoris in previously injured participants (coefficient = 23 Nm [95% CI = 7-40 Nm], adjusted R2 = 0.31, p = 0.01). There were no differences in markers of corticospinal excitability between previously injured and control limbs (all p > 0.24, all Cohen's d < 0.40). Athletes with previous injury in the biceps femoris exhibit increased SICI in this muscle compared with control participants. Increased SICI is related to lower levels of hamstring strength, and rehabilitation programs targeting the removal of intra-cortical inhibition should be considered.


Improvements to a Markerless Allelic Exchange System for Bacillus anthracis.
A system was previously developed for conducting I-SceI-mediated allelic exchange in Bacillus anthracis. In this system, recombinational loss of a chromosomally-integrated allelic exchange vector is stimulated by creation of a double-stranded break within the vector by the homing endonuclease I-SceI. Although this system is reasonably efficient and represents an improvement in the tools available for allelic exchange in B. anthracis, researchers are nonetheless required to "pick and patch" colonies in order to identify candidate "exchangeants." In the present study, a number of improvements have been made to this system: 1) an improved I-SceI-producing plasmid includes oriT so that both plasmids can now be introduced by conjugation, thus avoiding the need for preparing electro-competent cells of each integration intermediate; 2) antibiotic markers have been changed to allow the use of the system in select agent strains; and 3) both plasmids have been marked with fluorescent proteins, allowing the visualization of plasmid segregation on a plate and obviating the need for "picking and patching." These modifications have made the process easier, faster, and more efficient, allowing for parallel construction of larger numbers of mutant strains. Using this improved system, the genes encoding the tripartite anthrax toxin were deleted singly and in combination from plasmid pXO1 of Sterne strain 34F2. In the course of this study, we determined that DNA transfer to B. anthracis could be accomplished by conjugation directly from a methylation-competent E. coli strain.


Erosive tooth Wear in special Olympic athletes with intellectual disabilities.
Special Olympics (SO) events represent an opportunity to obtain considerable information regarding intellectual disable (ID) patients. Studies done with SO data have shown an overview of the oral health status of these athletes; however, no information exists regarding the erosive tooth wear (ETW). Therefore, the aim of this study is to determine the presence and severity of ETW in athletes with ID who participated in the SO Belgium 2016. The study population consisted in 232 athletes with ID who participated in the SO special smiles program, Belgium 2016. For analysis, the sample was divided in three groups: a) athletes with ID under the age of 25 not diagnosed with Down Syndrome (DS) (n = 174), b) athletes with DS under the age of 25 (n = 39) and c) athletes with DS from 25 and older ages (n = 58). Two calibrated dentists performed dental examinations using the Basic Erosive Wear Examination Index (BEWE). The BEWE sum > 0 was used to determine prevalence of ETW. Severity was determined by two- indicators: 1) By risk levels (low, medium and high risk) proposed by the BEWE index, and 2) by the highest score reached per subject in at least one tooth (BEWE1, 2 or 3). Chi-square test and Mann-Whitney U test were used to detect significant differences among different groups (p < 0.05). The prevalence of ETW for young athletes with ID was 51.14%. Within these athletes, the DS group presented a significant higher mean BEWE sum (4.67, SD 5.64) and prevalence of ETW (69.2%BEWE> 0) when compared to athletes without DS (mean BEWE sum: 1.96, SD 3.47 and 46.3% BEWE> 0; p < 0.05). Furthermore, a significantly higher percentage of athletes with DS were considered at high risk of ETW (p < 0.05). As a conclusion, half of the young athletes with ID presented at least one affected surface with ETW. The recorded prevalence and severity of ETW for the younger group of athletes with DS was distinctly higher than the athletes with ID not having DS. This shows the need to generate knowledge in order to provide correct management and prevention of erosive tooth wear in populations with ID.


A nationwide system for computer recording of neuroradiologic examinations.
For 2 years the system of recording radiologic examinations connected with the computer called SYBAR has been in operation. The examination methods are coded using the Index of Roentgen Examinations of the Swedish National Medical Board (1970), while the diagnoses are coded according to [4]. The positive experience accumulated so far prompted the authors to project and put in operation the system NEURO-SYBAR in order to organize a bank of data of neuroradiologic examinations. This system required the widening of two anatomic fields, 'skull and contents' and 'spine and contents,' according to the 'Index for Roentgen Diagnoses' of the American College of Radiology [1]. The NEURO-SYBAR system was adopted by ten radiologic departments in the country. The complete neuroradiologic data from these departments were collected in one computer center in Lodz.


Recommendations on the Use of Oral Orthotic Occlusal Appliance Therapy for Temporomandibular Joint Disorders: Current Evidence and Clinical Practice.
'Temporomandibular joint disorders (TMDs)' denote an umbrella term that includes arthritic, musculoskeletal and neuromuscular conditions involving the temporomandibular joint, the masticatory muscles, and the associated tissues. Occlusal devices are one of the common treatment modalities utilized in the conservative management of TMDs. The indications for the available 'oral splints' or 'oral orthotic occlusal devices' remain ambiguous. A joint international consortium was formulated involving the subject experts at TMJ Foundation, to resolve the current ambiguity regarding the use of oral orthotic occlusal appliance therapy for the temporomandibular joint disorders based on the current scientific and clinical evidence. The recommendations and the conclusion of the clinical experts of the joint international consort has been summarized for understanding the indications of the various available oral orthotic occlusal appliances and to aid in the future research on oral occlusal orthotics. The use of the oral orthotic occlusal appliances should be based on the current available scientific evidence, rather than the archaic protocols.


Left atrial appendage closure for stroke prevention in nonvalvular atrial fibrillation: A current overview.
Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice and its prevalence increases with age. AF causes palpitations, heart failure, and cardiogenic embolism. Of them, the most critical and fatal complication is a cardio-embolic event. Oral anticoagulation plays a central role in reducing stroke risk in AF patients. Recently, when oral anticoagulation is considered in patients with non-valvular AF who are eligible for direct oral coagulations, they are preferred to vitamin K antagonist based on accumulating evidence. Although many patients can tolerate oral anticoagulation, there is a subset of patients who cannot tolerate long-term oral anticoagulation. Such a subset has a higher bleeding risk as indicated by the HAS-BLED score under oral anticoagulation. This subset of patients requires effective and safe non-pharmacological alternative therapies for stroke prevention. One of the promising non-pharmacological therapies is left atrial appendage closure. Three randomized controlled trials demonstrated non-inferiority of percutaneous left atrial appendage closure using WATCHMAN family to oral anticoagulation (Boston Scientific, Marlborough, MA, USA). WATCHMAN FLX, which was innovated following WATCHMAN 2.5, was associated with fewer safety events and a higher success rate of effective appendage closure. Nevertheless, several unsolved issues remain, including device-related thrombosis, post-treatment antithrombotic therapy, and peri-device leakage. Left atrial appendage closure for patients with non-valvular AF may be an alternative therapy to avoid cardiac embolism for high bleeding risk patients with contraindications to long-term oral anticoagulation therapy.


Non-specific binding to protein A Sepharose and protein G Sepharose in insulin autoantibody assays may be reduced by pre-treatment with glycine or ethanolamine.
Insulin autoantibody (IAA) microassays are widely used for predicting type 1 diabetes. As levels of IAA are often low in type 1 diabetes, non-specific binding (NSB) needs to be minimised if assays are to achieve high analytical sensitivity. IAA microassays use protein A Sepharose (PAS) or protein G Sepharose (PGS) to isolate the antibody-bound label, but NSB by the gel can differ between commercially-produced batches. We investigated whether pre-incubation of gel with glycine or ethanolamine could overcome this problem. Batches of PAS/PGS shown to have high NSB (0.3-3.2%) were incubated with glycine or ethanolamine at various pHs between 8 and 10.6 for 2-18 h at 4 degrees C or room temperature. Treating PAS at pH 10.6 with 0.2 M glycine overnight at room temperature reduced NSB by >84%, with minimal reduction in specific binding (<5%). Treating PGS at pH 10.6 with 0.2 M ethanolamine overnight at 4 degrees C reduced background by >95%, with minimal reduction in specific binding by most sera. Treatment at high pH was critical in reducing NSB to both PAS and PGS, with slight reduction at pH 8, but a major reduction at pH 10.6. Pre-treatment with glycine or ethanolamine allows "poor" batches of PAS or PGS to be used in sensitive IAA assays, improving both consistency and performance.


ATP formation onset lag and post-illumination phosphorylation initiated with single-turnover flashes. III. Characterization of the ATP formation onset lag and post-illumination phosphorylation for thylakoids exhibiting localized or bulk-phase delocalized energy coupling.
When 100 mM KCl replaced sucrose in a chloroplast thylakoid stock suspension buffer, the membranes were converted from a localized proton gradient to a delocalized proton gradient energy coupling mode. The KCl-suspended but not the sucrose-suspended thylakoids showed pyridine-dependent extensions of the ATP onset lag and pyridine effects on post-illumination phosphorylation. The ATP formation assays were performed in a medium of identical composition, using about a 200-fold dilution of the stock thylakoid suspension; hence the different responses were due to the pretreatment, and not the conditions present in the phosphorylation assay. Such permeable buffer effects on ATP formation provide a clear indicator of delocalized proton gradients as the driving force for phosphorylation. The pyridine-dependent increases in the onset lags (and effects on post-illumination phosphorylation) were not due to different ionic conductivities of the membranes (measured by the 515 nm electrochromic absorption change), H+/e- ratios, or electron transport capacities for the two thylakoid preparations. Thylakoid volumes and [14C]pyridine equilibration were similar with both preparations. The KCl-induced shift toward a bulk-phase delocalized energy coupling mode was reversed when the thylakoids were placed back in a low-salt medium. Proton uptake, at the ATP-formation energization threshold flash number, was much larger in the KCl-treated thylakoids and they also had a longer ATP formation onset lag, when no pyridine was present. These results are consistent with the salt treatment exposing additional endogenous buffering groups for interaction with the proton gradient. The concomitant appearance of the pyridine buffer effects implies that the additional endogenous buffering groups must be located on proteins directly exposed in the aqueous lumen phase. Kinetic analysis of the decay of the post-illumination phosphorylation in the two thylakoid preparations showed different apparent first-order rate constants, consistent with there being two different compartments contributing to the proton reservoirs that energize ATP formation. We suggest that the two compartments are a membrane-phase localized compartment operative in the sucrose-treated thylakoids and the bulk lumen phase into which protons readily equilibrate in the KCl-treated thylakoids.


Physical and functional evaluations in oncological patients elective to medium and large operations.
To evaluate the risk of sarcopenia on the length of hospital stay and deaths in preoperative cancer patients as well its relation to physical and functional capacity. Preoperative patients admitted to the Cancer Hospital of Mato Grosso comprised the sample. Sociodemographic data, lifestyle data, and a questionnaire for sarcopenia screening were collected. Subsequently, total body mass, height, muscle strength, muscle mass, and physical performance were evaluated. The primary, secondary and tertiary outcomes were sarcopenia, length of stay and death, respectively. The data were tabulated and analyzed using the statistical software SPSS (25.0). The significance level was 5%. We observed 12 (7.4%) patients with low muscle strength, 20 (12.3%) patients with low muscle mass, 11 (6.8%) patients with low physical performance, and 18 (11.1%) patients with scores for possible sarcopenia. When the risk of sarcopenia was observed, 44 (27.2%) patients had at least one risk related to muscle disorder. When analyzing the prevalence and association of sarcopenia with sociodemographic variables, we observed that education level was associated with sarcopenia (p = 0.031). In addition, there was an association between preoperative sarcopenia and postoperative death (p = 0.006). Finally, there were important correlations between muscle strength and physical performance (p < 0.05), between muscle strength and the sarcopenia questionnaire (p < 0.001), and between physical performance and the sarcopenia questionnaire (p < 0.05). The results suggest the need for counseling and the need to evaluate patients for risk of sarcopenia, since early intervention, such as dietary supplementation and physical exercise, may favor a better postoperative prognosis, possibly corresponding to shorter hospital stays and longer survival and quality of life for patients, especially those who will undergo surgical procedures.


Upper endoscopy photodocumentation quality evaluation with novel deep learning system.
Visualization and photodocumentation during endoscopy procedures are suggested to be one indicator for endoscopy performance quality. However, this indicator is difficult to measure and audit manually in clinical practice. Artificial intelligence (AI) is an emerging technology that may solve this problem. A deep learning model with an accuracy of 96.64% was developed from 15,305 images for upper endoscopy anatomy classification in the unit. Endoscopy images for asymptomatic patients receiving screening endoscopy were evaluated with this model to assess the completeness of photodocumentation rate. A total of 15,723 images from 472 upper endoscopies performed by 12 endoscopists were enrolled. The complete photodocumentation rate from the pharynx to the duodenum was 53.8% and from the esophagus to the duodenum was 78.0% in this study. Endoscopists with a higher adenoma detection rate had a higher complete examination rate from the pharynx to duodenum (60.0% vs. 38.7%, P < 0.0001) and from esophagus to duodenum (83.0% vs. 65.7%, P < 0.0001) compared with endoscopists with lower adenoma detection rate. The pharynx, gastric angle, gastric retroflex view, gastric antrum, and the first portion of duodenum are likely to be missed by endoscopists with lower adenoma detection rates. We report the use of a deep learning model to audit endoscopy photodocumentation quality in our unit. Endoscopists with better performance in colonoscopy had a better performance for this quality indicator. The use of such an AI system may help the endoscopy unit audit endoscopy performance.


The impact of marital status at diagnosis on cancer survival in patients with differentiated thyroid cancer.
Previous studies have revealed that marital status influences the prognosis of patients with various types of cancer. We evaluated the influence of marriage on the survival outcomes in differentiated thyroid cancer (DTC). The Surveillance, Epidemiology and End Results (SEER) database between 2002 and 2012 was used to compare cancer-specific mortality in different marital status, and in each sex, age, and stage stratification by multivariate Cox regression model. In total, 61,077 eligible patients were identified. The widowed group had the highest proportion of women, elderly patients (≥45 years), and advanced stage III/IV tumor (P = 0.001), but the total thyroidectomy (TT) performed and radioisotopes therapy rates were lower than those in the married group. Married patients had a better cancer-specific survival (CSS) than the unmarried (P < 0.05). Further analysis showed that widowed patients always presented the lowest CSS compared with other groups. Widowed patients had a significant increased risk for CSS compared with married patients in males [hazard ratio (HR) 2.72, 95% confidence interval (CI): 1.59-4.65, P = 0.001], females (HR 2.02, 95% CI: 2.24-4.06, P = 0.001), young patients (<45, HR 28.12, 95% CI: 3.48-227.25, P = 0.002), elderly patients (≥45, HR 28.12, 95% CI: 2.97, 95% CI: 2.30-3.83, P = 0.001), stage I (HR 8.44, 95% CI: 4.05-17.59, P = 0.001), stage II (HR 3.64, 95% CI: 1.30-10.20, P = 0.014), stage III (HR 2.27, 95% CI: 1.08-4.78, P = 0.031), and stage IV (HR 2.63, 95% CI: 1.94-3.57, P = 0.001). These results showed that unmarried status, especially for widowhood, increased the risk of cancer mortality in DTC patients.


Spectrodensitometric determination of trichothecene mycotoxins with 4-(p-nitrobenzyl)pyridine on silica gel thin-layer chromatograms.
A simple method for the detection and spectrodensitometric determination of a number of trichothecene mycotoxins on silica gel layers based on a colour reaction between 4-(p-nitrobenzyl)pyridine and the 12,13-epoxy group in the trichothecene nucleus is described. The detection limits for the twelve trichothecenes examined were 0.025--0.2 micrograms per spot. Further, six of the twelve trichothecenes could be determined spectrodensitometrically in the range from ca. 0.05--0.2 to 10 micrograms per spot with a coefficient of variation of ca. 5%.


Satellite cell pool expansion is affected by skeletal muscle characteristics.
We investigated changes in satellite cell (SC) pool size after an acute bout of strenuous exercise and evaluated the influence of baseline SC count and fiber type. Participants completed a downhill running (DHR) intervention (5 × 8 min, 2-min rest; 80% VO2max ; -10% gradient). Muscle biopsies were taken 7 days before VO₂max and 7-9 days after the DHR intervention. Delayed-onset muscle soreness (DOMS) and creatine kinase activity (CK) were measured on days 1, 2, 7, and 9 post-DHR. SCs were identified by Pax7 and laminin staining. Relative distribution of MHC isoforms was determined by electrophoresis. DOMS and CK peaked on day 1 post-DHR (P < 0.01). The SC pool increased (26%) after DHR (P = 0.005). SCs/total myonuclei after recovery correlated with baseline SCs (r = 0.979, P = 0.003) and VO₂max (r = 0.956, P = 0.011), whereas change in SC pool (Pax7(+) cells/total myonuclei: recovery minus baseline) tended to correlate with percent MHC II (r = 0.848; P = 0.06). Interindividual physiological characteristics affect SC pool expansion after a single bout of DHR and are influenced by VO₂max .


Removal of dissolved metals by zero-valent iron (ZVI): kinetics, equilibria, processes and implications for stormwater runoff treatment.
Infiltration of stormwater runoff contaminated with metals is often questionable in several cases due to its long-term potential to cause deterioration of groundwater quality. To ensure the quality of filtrate, a pre-treatment of contaminated runoff is required. This study investigates the processes of copper and zinc ion removal from stormwater runoff using zero-valent iron (ZVI, Fe0). Kinetic and equilibrium tests were performed with laboratory-prepared and in situ stormwater runoff samples collected from roof, street and highway catchments. Based on the results, a substantial portion of Cu2+ is reduced and transformed to insoluble forms of Cu0 and Cu2O. Unlike copper, the adsorption and co-precipitation associated with freshly precipitated iron oxides play important roles for the removal of Zn2+. Investigations under various water quality conditions demonstrated a relatively minor impact on Cu2+ uptake rates. However, the different conditions apparently altered the removal stoichiometry and phases of the copper deposits. The removal rates of Zn2+ increase with higher dissolved oxygen (DO), ionic strength (IS), temperature (T) and pH. Dissolved organic carbon (DOC) in runoff samples forms complexes with metals and Fe2+, thereby kinetically decreasing the metal uptake rates. Furthermore, depending on its composition, a larger molecular weight organic fraction was found to preferentially compete for the adsorption sites. The study demonstrates that ZVI is a promising medium for achieving comparable capacity to a commercial adsorbent like granular ferric hydroxide (GFH). Long-term performance of ZVI, however, may be limited and governed by the formation of non-conductive layers of iron and cuprous oxides.


Elevated IgA Plasmablast Levels in Subjects at Risk of Developing Rheumatoid Arthritis.
The disease process in rheumatoid arthritis (RA) starts years before the clinical diagnosis is made, and elevated levels of disease-specific autoantibodies can be detected during this period. Early responses to known or novel autoantigens likely drive the eventual production of pathogenic autoimmunity. Importantly, the presence of disease-specific autoantibodies can identify individuals who are at high risk of developing RA but who do not currently have arthritis. The goal of the current study was to characterize plasmablasts from individuals at risk of developing RA. We investigated antibody-secreting plasmablasts derived from a well-characterized cohort of individuals who were at risk of developing RA, based on RA-related serum autoantibody positivity, as compared to patients with early (<1 year) seropositive RA as well as healthy control subjects. The plasmablast antibody repertoires of at-risk subjects were analyzed using DNA barcode-based methods with paired heavy- and light-chain gene sequencing. Cells were single-cell sorted, the cell- and plate-specific DNA barcodes were sequentially added, and next-generation sequencing was performed. Total plasmablast levels were similar in the antibody-positive (1%) and control (0.4-1.6%) groups. However, increased frequencies of IgA+ versus IgG+ plasmablasts were observed in the antibody-positive group (39% IgA+ and 37% IgG+) as compared to other groups (1-9% IgA+ and 71-87% IgG+). Paired antibody sequences from antibody-positive subjects revealed cross-isotype clonal families and similar sequence characteristics in the IgA and IgG plasmablast repertoires. Antibody-positive individuals also demonstrated elevated serum levels of IgA isotype anti-cyclic citrullinated peptide 3 antibodies. The IgA plasmablast dominance in these antibody-positive individuals suggests that a subset of RA-related autoantibodies may arise from mucosal immune responses and may be involved in early disease pathogenesis in individuals who are at risk of developing RA.


[Experiences with the use of a lyophilized reference plasma for calibrating the determination of thromboplastin time values].
Experiences are notified about production and employment of a lyophilised standard plasma for designation of thromboplastin time-value in the district Magdeburg. In addition to testing the homogeneity and the methodology for declaration the 100% - value results of ring tests are exhibited, which underline the necessity of a unitary standard plasma pool, secured to various criterions.


Nephrotoxicity of 1,1-diaminomethylcyclohexane sulphato platinum II (spiroplatin; TNO-6).
1,1-Diaminomethylcyclohexane sulphato platinum II (spiroplatin; TNO-6) is a new platinum-containing analog used as an antitumor agent. Renal function studies were performed in eight patients treated with this drug (30 mg/m2). During and after the first spiroplatin infusion there was a decrease in effective renal plasma flow (ERPF:P less than 0.05) and an increase in filtration fraction (P less than 0.01) without changes in glomerular filtration rate (GFR), suggesting changes in renal hemodynamics. During the same period there was an increase in relative N-acetyl-beta-D-glucosaminidase excretion (P less than 0.01), pointing to tubular cell damage. Also, an increase in relative beta 2-microglobulin excretion was established during and after spiroplatin infusion. On day 21 a decrease in GFR was found (median 7.4%), together with a decrease in ERPF (median 11.8%).


Poly(Ethylene Glycol) Diacrylate as the Passivation Layer for High-Performance Perovskite Solar Cells.
In the past decade, greatest effect has been paid on organic-inorganic halide perovskites for approaching high-performance perovskite solar cells (PSCs). It was found that severe surface-defect within the perovskite active layer restricted further boosting device performance of PSCs. Here, we report high-performance PSCs by utilization of an ultrathin solution-processed poly(ethylene glycol) diacrylate (PEGDA) layer to passivate the surface-defect within the perovskite thin film. Systematical studies demonstrate that the PEGDA-passivated perovskite thin film exhibit suppressed nonradiative recombination and trap density, as well as superior film morphology with a smoother surface, larger crystal size, and better crystallinity. Moreover, PSCs by the PEGDA-passivated perovskite thin film exhibit suppressed charge carrier recombination, reduced charge-transfer resistance, shorter charge carrier extraction time, and enlarged built-in potential. As a result, PSCs by the PEGDA-passivated perovskite thin film show a power conversion efficiency of over 21% and a photocurrent hysteresis index of 0.037. Moreover, unencapsulated PSCs by the PEGDA-passivated perovskite thin film possess over 10 day operational stability. All these results indicate that our approach provided a facile way to boost device performance of PSCs.


Rapidly adapting receptor activity during oxidative stress induced airway hyperresponsiveness.
The responses of airway rapidly adapting receptors (RARs) to ovalbumin challenge and histamine were investigated in guinea pigs which were sensitized with ovalbumin. Sensitization alone increased the basal RAR activity. Antigen challenge stimulated them. Histamine doses which caused a 50% increase in airway resistance (ED50) were reduced immediately and 24h after antigen challenge indicating respectively early and late onset airway hyperresponsiveness. At these doses, there was a greater stimulation of the RARs compared to controls. An increase in lipid peroxidation and a decrease in glutathione peroxidase were observed also. With oral intake of vitamins C and E, attenuations in the basal RAR activity, the responses of RARs to antigen challenge and the oxidative stress were observed. With an increase in ED50, the RAR response to histamine became similar as in control. It is concluded that by decreasing the RAR responses to allergen and histamine, antioxidants may reduce reflex bronchoconstriction occurring in asthmatics.


Ultrastretchable, self-adhesive, strain-sensitive and self-healing GO@DA/Alginate/P(AAc-co-AAm) multifunctional hydrogels via mussel-inspired chemistry.
For conductive hydrogels applied in biosensors, wearable devices and so forth, multifunctionality is an inevitable trend of development to meet various practical requirements and enhance human experience. Herein, inspired by nanocomposite, double-network (DN) and mussel chemistry, a new Graphene oxide@Dopamine/Alginate/Poly(acrylic acid-co-acrylamide) [GO@DA/Alginate/P(AAc-co-AAm)] hydrogel was fabricated through one-pot in-situ radical copolymerization. GO@DA nanofillers, prepared via GO confined DA polymerization, imparted the hydrogel with remarkable adhesiveness. Alginate/P(AAc-co-AAm) DN matrix, physically and chemically crosslinked by Fe3+ and N,N'-Methylenebisacrylamide, made hydrogels ultrastretchable, self-healing and biocompatible. With contents of DA and alginate accurately regulated, the tensile strength, elongation, adhesion strength and conductivity of the optimal hydrogel could reach 320.2 kPa, 1198 %, 36.9 kPa and 3.24 ± 0.12 S/m, respectively. What's more notable was that the synergistic integration of repeatable adhesiveness, strain sensitivity, use stability, self-healing ability and biocompatibility provided such hydrogels with tremendous possibility of practical application for strain sensors.


Self-cleavage of RNA in the replication of small pathogens of plants and animals.
The ability of certain small, circular, pathogenic RNAs of plants and animals to self-cleave at specific sites in vitro in the complete absence of protein most likely plays a central role in their replication in vivo by a rolling circle mechanism. The self-cleavage of an RNA transcript from a satellite DNA of the newt indicates that this reaction is not limited to pathogenic RNAs. Further, the site-specific self-cleavage in trans by two separate RNA molecules suggests that such reactions may be important in gene regulation in normal cells as well as in the genesis of symptom expression on infection by RNA pathogens.


Polyphasic taxonomy of green algae strains isolated from Mediterranean freshwaters.
Terrestrial, freshwater and marine green algae constitute the large and morphologically diverse phylum of Chlorophyta, which gave rise to the core chlorophytes. Chlorophyta are abundant and diverse in freshwater environments where sometimes they form nuisance blooms under eutrophication conditions. The phylogenetic relationships among core chlorophyte clades (Chlorodendrophyceae, Ulvophyceae, Trebouxiophyceae and Chlorophyceae), are of particular interest as it is a species-rich phylum with ecological importance worldwide, but are still poorly understood. In the Mediterranean ecoregion, data on molecular characterization of eukaryotic microalgae strains are limited and current knowledge is based on ecological studies of natural populations. In the present study we report the isolation and characterization of 11 green microalgae strains from Greece contributing more information for the taxonomy of Chlorophyta. The study combined morphological and molecular data. Phylogenetic analysis based on 18S rRNA, internal transcribed spacer (ITS) region and the large subunit of the ribulose-bisphosphate carboxylase (rbcL) gene revealed eight taxa. Eleven green algae strains were classified in four orders (Sphaeropleales, Chlorellales, Chlamydomonadales and Chaetophorales) and were represented by four genera; one strain was not assigned to any genus. Most strains (six) were classified to the genus Desmodesmus, two strains to genus Chlorella, one to genus Spongiosarcinopsis and one filamentous strain to genus Uronema. One strain is placed in a separate independent branch within the Chlamydomonadales and deserves further research. Our study reports, for the first time, the presence of Uronema in an aquatic environment up to 40 °C and reveals new diversity within the Chlamydomonadales. The results from the ITS region and the rbcL gene corroborated those obtained from 18S rRNA without providing further information or resolving the phylogenetic relationships within certain genera, due to the limited number of ITS and rbcL sequences available. The comparison of molecular and morphological data showed that they were congruent. Cosmopolitan genera with high worldwide distribution inhabit Greek freshwaters.


Comparison of Cochlear Implantation Complications with Subperiosteal Pocket Technique Versus Well-Drilling Technique in Pediatric Patients: A Retrospective Study.
Aims: Cochlear implantation is becoming the standard treatment for rehabilitating patients with sensorineural hearing (SNH) impairment. Various techniques can be used to achieve this goal. In the current study, we compared the subperiosteal technique (SPT) with the development of a subperiosteal pocket without fixation to the well-drilling method (WD) by constructing an incision into the scalp with suture fixation. Materials and methods: Our study weighted the efficiency of children who underwent WD or SPT from 2017 to 2021 at King Abdulaziz University Hospital. In this retrospective records review, we compared 63 SPT cases with 104 WD cases during a 5-year period who were followed for 1 month or more. Results: There were 88 females (50.9%) and 79 male (45.7%) with a mean age of 4.49 ± 3.06 years at the time of surgery. The mean WD duration was 2.47 ± 1.05 h, and 2.91 ± 1.05 h for SPT (P = 0.01). Moreover, there was a significant relationship between comorbidities and electrode complications (P = 0.022). There was no significant correlation between the surgical method and intraoperative complications (P = 0.714), electrode array issues (P = 0.88), or serious postoperative complications including device failure and migration skin problems (P = 0.207). Conclusion: Overall, the WD technique was faster. However, both methods can be used safely and effectively, as no significant intraoperative or postoperative complications were observed. Further long-term studies are required to validate our findings. The online version contains supplementary material available at 10.1007/s12070-023-03735-z.


"In-source" fragmentation of an isobaric impurity of lamotrigine for its measurement by liquid chromatography tandem mass spectrometry after pre-concentration using solid phase extraction.
An analytical method has been developed for trace analysis (i.e. sub-ppm levels) of a key synthetic impurity, 14W80 ((Z)-2-(2,3-dichlorophenyl)-2-(guanidinylimino)acetonitrile) in lamotrigine (3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine). 14W80 is isobaric with lamotrigine, which gives an extra layer of complexity to its determination and the various problems associated with development of an appropriate methodology are discussed in this work. Ultimately, a liquid chromatography tandem mass spectrometry (LC-MS/MS) method using in-source fragmentation with Atmospheric Pressure Chemical Ionisation (APCI) followed by multiple reaction monitoring (MRM) has been found to provide adequate sensitivity and specificity. A detection limit of 25 ppb mass fraction relative to lamotrigine was achieved for 14W80. The use of solid phase extraction (SPE) enhanced the detection limit to 2 ppb mass fraction relative to lamotrigine.


Growth-differentiation factor-15 and functional outcome after acute ischemic stroke.
Blood biomarkers may improve the performance in predicting early stroke outcome beyond well-established clinical factors. We investigated the value of growth-differentiation factor-15 (GDF-15) to predict functional outcome after 90 days in a prospectively collected patient cohort with symptoms of acute ischemic stroke. Two hundred eighty-one patients with symptoms of acute ischemic stroke were prospectively investigated. Serial blood samples for GDF-15 analysis were obtained after the admission of the patient, after 6 and 24 h. Primary outcome was the dichotomized modified ranking scale (MRS) 90 days after the initial clinical event. Within the final study population (264 patients, mean age 70.3 ± 12.7 years, 55.3% male), National Institutes of Health Stroke Scale (NIH-SS) [odds ratio (OR) 1.269, 95% confidence interval (CI) 1.141-1.412, p < 0.001] and initial GDF-15 levels (OR 1.029, 95% CI 1.007-1.053, p = 0.011) were independently associated with a MRS ≥ 2 after day 90 after multiple regression analysis. Growth-differentiation factor-15 levels increase with higher NIH-SS-tertiles (p = 0.005). Receiver-operator characteristic curves demonstrated a discriminatory accuracy to predict unfavourable stroke outcome of 0.629 (95% CI 0.558-0.699), 0.753 (95% CI 0.693-812) and 0.774 (95% CI 0.717-0.832) for GDF-15, NIH-SS and the combination of these variables. The additional use of GDF-15 to NIH-SS ameliorates the model with a net reclassification index of 0.044 (p = 0.541) and integrated discrimination improvement of 0.034 (p = 0.443). Growth-differentiation factor-15 as an acute stroke biomarker independently predicts unfavourable functional 90 day stroke outcome. Discriminatory value in addition to NIH-SS is only modestly distinct.


In Situ Quantification of Surface Chemistry in Porous Collagen Biomaterials.
Cells inside a 3D matrix (such as tissue extracellular matrix or biomaterials) sense their insoluble environment through specific binding interactions between their adhesion receptors and ligands present on the matrix surface. Despite the critical role of the insoluble matrix in cell regulation, there exist no widely-applicable methods for quantifying the chemical stimuli provided by a matrix to cells. Here, we describe a general-purpose technique for quantifying in situ the density of ligands for specific cell adhesion receptors of interest on the surface of a 3D matrix. This paper improves significantly the accuracy of the procedure introduced in a previous publication by detailed marker characterization, optimized staining, and improved data interpretation. The optimized methodology is utilized to quantify the ligands of integrins α 1 β 1, α 2 β 1 on two kinds of matched porous collagen scaffolds, which are shown to possess significantly different ligand density, and significantly different ability to induce peripheral nerve regeneration in vivo. Data support the hypothesis that cell adhesion regulates contractile cell phenotypes, recently shown to be inversely related to organ regeneration. The technique provides a standardized way to quantify the surface chemistry of 3D matrices, and a means for introducing matrix effects in quantitative biological models.


Jasmonic acid deficiency leads to scattered floret opening time in cytoplasmic male sterile rice Zhenshan 97A.
Cytoplasmic male sterile (CMS) rice has been widely used for hybrid rice seed production in China. However, CMS rice suffers from undesirable flowering habits including scattered floret opening time (FOT), which causes different FOTs among parental rice plants and greatly reduces hybrid rice seed production. Little is known about the mechanism of scattered FOT in CMS rice. Our results demonstrate that scattered FOT in CMS rice Zhenshan 97A (ZS97A) resulted from the lack of a driving force to open florets, which was directly caused by retarded lodicule expansion. Our results indicate that retarded lodicule expansion in ZS97A was caused by reduced water accumulation due to retarded accumulation of osmotic regulation substances (ORSs). Further, the retardation in accumulation of ORSs and water were caused by jasmonic acid (JA) deficiency, resulting from down-regulation of OsAOC expression. Applying JA restored scattered FOT in ZS97A by promoting ORS and water accumulation, and inducing the expansion of the lodicules. Taken together, JA deficiency inhibited lodicule expansion by retarding the accumulation of ORSs and water, leading to scattered FOT in CMS rice ZS97A.


Variability in qualifications for principal investigator status in research studies by nurses: A call for clarification.
To describe existing guidance for qualifications of principal investigator s (PI s) of human subjects research and explore how they are operationalized for pediatric nurse scientists and clinical nurses in children's hospitals. After reviewing federal regulations, accreditation guidelines, and the literature, a convenience sample of members of the National Pediatric Nurse Scientist Collaborative (NPNSC). Participants completed a 33-item survey that included questions about Institutional Review Board (IRB), guidelines, and policies for PI status at their affiliated children's hospitals. The survey was electronically disseminated to 179 members of NPNSC through the Collaborative's listserv. Of the 39 members who responded, 90% hold a PhD and 80% practice in a free-standing children's hospital, nearly all of which (93%) are recognized as Magnet® hospitals. While the majority of respondents indicated that nurse scientists and other nurses were allowed to be PIs of research studies, educational requirements for PI status varied, with 3% requiring a PhD, 15% a baccalaureate degree, and 10% a graduate degree. 54% of respondents reported there was no degree requirement for PI status; however15% reported that even doctorally prepared nurse scientists cannot serve as PIs of research studies at their affiliated children''s hospitals. The survey identified substantial variability in requirements for PI status and potential barriers to pediatric nurses conducting independent research as PIs at children's hospitals. Operationalizing existing guidance will expand inclusion of nurse scientist expertise in human subjects research.


Peroxisome proliferator-activated receptor-γ (PPARγ) agonist is neuroprotective and stimulates PGC-1α expression and CREB phosphorylation in human dopaminergic neurons.
Mitochondrial dysfunction has been linked to several neurodegenerative diseases such as Parkinson's disease (PD). Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a master gene for mitochondrial biogenesis and has been shown to be neuroprotective in models of PD. In this work we have studied the mechanisms by which peroxisome proliferator-activated receptor-γ (PPARγ) selective agonist N-(2-benzoylphenyl)-O-[2-(methyl-2-pyridinylamino)ethyl]-l-tyrosine hydrate (GW1929) acts on human dopaminergic neurons in culture. Data showed that GW1929 increased the viability of human dopaminergic neurons and protected them against oxidative stress induced by H2O2 and the mitochondrial toxin Rotenone. The enhanced resilience of the neurons was attributed to increased levels of mitochondrial antioxidants and of PGC-1α. GW1929 treatment further increased cell respiration, mitochondrial biogenesis and sirtuin-1 (SIRT1) expression in the human dopaminergic neurons. Phosphorylation of cAMP responsive element-binding protein (CREB) was also robustly increased in GW1929-treated cells. Together these results show that the PPARγ agonist GW1929 influences CREB signaling and PGC-1α activities in the human dopaminergic neurons contributing to an increased cell viability. This supports the view that drugs acting on the PPARγ-PGC-1α signaling in neurons may have beneficial effects in PD and possible also in other brain disorders.


Modeling Interactions of Erythromycin Derivatives with Ribosomes.
Using a method of static simulation, a series of erythromycin A analogs was designed with aldehyde functions introduced instead of one of the methyl substituents in the 3'-N-position of the antibiotic that was potentially capable of forming a covalent bond with an amino group of one of the nucleotide residues of the 23S rRNA in the ribosomal exit tunnel. Similar interaction is observed for antibiotics of the tylosin series, which bind tightly to the large ribosomal subunit and demonstrate high antibacterial activity. Binding of novel erythromycin derivatives with the bacterial ribosome was investigated with the method of fluorescence polarization. It was found that the erythromycin analog containing a 1-methyl-3-oxopropyl group in the 3'-N-position demonstrates the best binding. Based on the ability to inhibit protein biosynthesis, it is on the same level as erythromycin, and it is significantly better than desmethyl-erythromycin. Molecular dynamic modeling of complexes of the derivatives with ribosomes was conducted to explain the observed effects.


Hydrophobic polymer monoliths as novel phase separators: application in continuous liquid-liquid extraction systems.
Hydrophobic macroporous polymer monoliths are shown to be interesting materials for the construction of "selective solvent gates". With the appropriate surface chemistry and porous properties the monoliths can be made permeable only for apolar organic solvents and not for water. Different poly(butyl methacrylate-co-ethylene dimethacrylate) (BMA-EDMA) and poly(styrene-co-divinylbenzene) (PS-DVB) monoliths prepared with tailored chemistries and porosities were evaluated for this purpose. After extensive characterization, the PS-DVB monoliths were selected due to their higher hydrophobicity and their more suitable flow characteristics. BMA-EDMA monoliths are preferred for mid-polarity solvents such as ethyl acetate, for which they provide efficient separation from water. Breakthrough experiments confirmed that the pressures necessary to generate flow of organic solvents through PS-DVB monoliths were substantially lower than for water. A phase separator was constructed using the monoliths as the flow selector. This device was successfully coupled on-line with a chip-based continuous liquid-liquid-extraction (LLE) system with segmented flow. Efficient separation of different solvents was obtained across a wide range of flow rates (0.5-4.0 mL min(-1)) and aqueous-to-organic flow ratios (β=1-10). Good robustness and long life-time were also confirmed. The suitability of the device to perform simple, cheap, and reliable phase separation in a continuous LLE system prior to gas-chromatographic analysis was proven for some selected real-life applications.


Parenteral nutrition in patients with liver cirrhosis. Effects on circulating levels of glucose and hormones and on cerebral function.
The effects of 2 and 5 days of total parenteral nutrition (TPN; 70 g amino-acids, 100 g fat, 150 g glucose) on carbohydrate, fat and amino-acid levels and on cerebral function were investigated in 10 patients with alcoholic cirrhosis and 7 age-matched healthy controls. The results were compared to those after a standardised oral diet. During TPN, glucose concentrations increased slightly in both groups. Insulin concentrations also rose in both groups, but the rise was more pronounced in the patients, resulting in a 10-fold difference between the two groups after 6.5 hours (patients: 281 +/- 81 U/l; controls: 28 +/- 5 U/l; p < 0.02). Glucagon increased significantly during TPN in the patients only (33%, p < 0.05). Similar but less pronounced patterns were observed after the oral diet. The basal concentrations of free fatty acids and 3-OH-butyrate were higher in the patients than in the controls. However, during both oral and parenteral nutrition, the concentrations fell in both groups. For 3-OH-butyrate the difference between the groups disappeared, while the free fatty acid levels remained higher in the patients throughout the TPN administration. Basal triglyceride levels were similar in patients and controls and rose to a similar extent in both groups during TPN. Plasma amino-acid concentrations were typical for cirrhotic patients in the basal state: low levels of the branched-chain amino-acids (BCAA) and high concentrations of the aromatic amino-acids (AAA). During TPN BCAA, as well as AAA, increased in both patients and controls, resulting in unaltered BCAA AAA ratio. All patients performed poorly on psychometric tests (Number Connection Tests A and B; Digit Symbol) before the study, indicating subclinical encephalopathy. However, no deterioration was observed in any of the tests during five days of TPN. Similarly, EEG and visual evoked potentials were unchanged during the study, demonstrating that patients with severe alcoholic liver disease tolerate a balanced intravenous nutrition without adverse effects on cerebral function.


Obstructive sleep apnea, coronary calcification and arterial stiffness in patients with diabetic kidney disease.
Obstructive sleep apnea (OSA) may accelerate arterial calcification, but the relation remains unexplored in diabetic kidney disease (DKD). We examined the associations between OSA, coronary calcification and large artery stiffness in patients with DKD and reduced renal function. Patients with type 2 diabetes, estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 and urine albumin-creatinine ratio (UACR) > 30 mg/g were tested for OSA quantified by the apnea-hypopnea index (AHI, events/hour). Patients without OSA (AHI< 5) were compared to patients with moderate (AHI 15-29) or severe (AHI ≥30) OSA and underwent computed tomography angiography with coronary Agatston scoring (CAS) to quantify coronary calcification. Arterial stiffness was determined as carotid-femoral pulse wave velocity (PWV). Among 114 patients with acceptable AHI recordings had 43 no OSA, 33 mild OSA and 38 moderate-severe OSA. Mean age of the 74 patients completing the study was 71.5 ± 9.4 years (73% males), eGFR 32.2 ± 12.3 ml/min/1.73 m2 and UACR 533 (192-1707) mg/g. CAS (ln-transformed) was significantly higher in patients with OSA compared to patients without (6.6 ± 1.7 vs. 5.6 ± 2.4, p = 0.04), and the same was observed for PWV (11.9 ± 2.7 vs. 10.5 ± 2.2 m/s, p = 0.02). In multivariable linear regression analyses adjusted for sex, age, body mass index, UACR, and mean arterial pressure, moderate-severe OSA remained significantly associated with PWV but not with CAS. Dominance analysis revealed OSA as the third and second most important factor relative to CAS and PWV respectively. In DKD patients, moderate-severe OSA is a significant predictor of arterial stiffness but is not independently associated with coronary calcification.