Nine cases of acute gastric anisakiasis.
From 1983 to 1988, we treated 19 patients with acute gastritis which was highly suggestive of gastritis anisakiasis. Almost all of these patients complained of sharp, periodic, upper abdominal pains which occurred several hours after ingestion of raw fish. Among the 19 patients, 10 anisakis larvae from nine patients were successfully removed by endoscopic forceps. However, in the remaining 10 patients, who also showed the typical clinical course of anisakiasis, we could not find the anisakis larvae endoscopically. All 10 larvae were identified as stage III, anisakis type 1. The intolerable pain was relieved as soon as endoscopic removal of the larvae was accomplished in all nine patients. The purpose of this article was to report the clinical findings and emphasize the importance of early endoscopic management of acute gastric anisakiasis.


Effects of different photoperiods on flower opening, flower closing and circadian expression of clock-related genes in Iris domestica and I. dichotoma.
The circadian clock can entrain to forced light-dark cycles by adjusting the phases and periods of flower opening and closing in ephemeral flowers. The responses of circadian rhythms to the same light conditions differ from species. However, the differences in internal genetic mechanisms underlying the different responses between species remain unclear. Iris domestica and I. dichotoma have ephemeral flowers and significantly divergent flower opening and closing times. The effects of different photoperiods (continuous darkness, 4L20D, 8L16D, 12L12D, 16L8D, 20L4D and continuous white light) on flower opening and closing, and expression patterns of seven genes (CRYPTOCHROME 1, PHYTOCHROME B, LATE ELONGATED HYPOCOTYL, PSEUDO RESPONSE REGULATOR 95, PHYTOCHROME INTERACTING FACTOR 4-like, SMUX AUXIN UP RNA 64-like and senescence-associated gene 39-like) involved in the circadian regulation of flower opening and closing were compared between I. domestica and I. dichotoma. Flower opening and closing in the two species exhibited circadian rhythms under continuous darkness (DD), but showed arrhythmia in continuous white light (LL). In the two species, keeping robust rhythms, strong synchronicity, rapid progressions of flower opening and closing and reaching full opening stage required a dark period longer than 4 h. In light-dark cycles with dark periods longer than 4 h, flower opening and closing times of the two species delayed with the delay of dawn, and the degree to which flower opening time varies with the time of dawn was greater in I. dichotoma than in I. domestica. The arrhythmia of flower opening and closing under 20L4D and LL would result from the arrhythmic output signals rather than arrhythmia of oscillators and photoreceptors. The different responses of the two species to the change of photoperiods would be caused by the transcriptional differences of genes in the output pathway of circadian clock system rather than in the input pathway or oscillators.


The development of the fetal rat intestine and its reaction to maternal diabetes. I. Morphometrical analysis in normal conditions.
In rodents, the fetal intestine develops rapidly during the last 5 days of gestation. The present investigation describes the events which occur in the duodenum, jejunum and ileum of fetal Wistar rat from day 16.5 to 21.5. The first villi and microvilli as well as endocrine cells already appear at 17.5 days in the duodenal mucosae. Goblet cells are detected at 18.5 days. The structure of the intestinal mucosa at 21.5 days is similar to that of adults. The evolution was quantified by morphometric analysis. The external and inner circumference, the length of the villi profile and the increased absorption area due to the villi profile were measured. We demonstrated that the total enlargement of the luminal surface area due to the villi and the microvilli in the duodenum of the fetus at 21.5 days is similar to that in the adult duodenum. This morphometric analysis could be used to detect possible disturbances in the development of the fetal intestine.


[Indicator of periodontal therapeutic needs (CPITN) in adults aged between 35-44 years in Szczecin province].
The authors have studied parodontological therapeutic needs utilizing the indicator of needs (CPITN) in 122 adults (35-44 years old) living in a small city of Lobez and adjacent villages in Szczecin province. From the results obtained it follows that the greatest percentage of parodontological therapeutic needs referred to the third category of these needs (82.8%). The average number of sextances with dental deposits falling to 1 person was 2.3 and with gingival pockets of 6 mm or deeper--2.1. No person with healthy parodontium has been found. Significantly greater parodontological therapeutic needs have been found in men than in women.


Vertical Paper Analytical Devices Fabricated Using the Principles of Quilling and Kirigami.
Here we report the vertical paper analytical devices (vPADs) fabricated using the principles of quilling and kirigami. What differentiates the vPADs from conventional paper microfluidic devices is that the paper substrate used to fabricate the device is placed vertically to the device plane. The fabrication of vPADs with high precision is instrument-free, requiring no photolithography, printing or heating. Two- and three-dimensional vPADs are fabricated for multiplex colorimetric assays of four biochemical indicators and automated enzyme-linked immunosorbent assay of human myoglobin, respectively.


Quantitative localization of neurons projecting to the mouse main olfactory bulb.
Horseradish peroxidase conjugated to wheat germ agglutinin was used as the tracer to demonstrate the cells of origin of the main olfactory bulb (MOB) afferent fibers in the mouse. The neurons projecting to the olfactory bulb were counted by area to show the contribution of each brain area to the system of MOB afferents. The majority of neurons projecting to the MOB were found in the nucleus olfactorius anterior and the cortex cerebri, area pyriformis, being respectively 53.8% and 35.7% of the total number of labeled neurons counted. The average total number of neurons per mouse brain projecting to the MOB was about 146,600.


A Screening of Native (Poly)phenols and Gut-Related Metabolites on 3D HCT116 Spheroids Reveals Gut Health Benefits of a Flavan-3-ol Metabolite.
Epidemiological evidence suggests that a reduced risk of colorectal cancer (CRC) is correlated with high consumption of fruits and vegetables, which are major sources of fiber and phytochemicals, such as flavan-3-ols. However, it remains unknown how these phytochemicals and their specific gut-related metabolites may alter cancer cell behavior. A focused screening using native (poly)phenols and gut microbial metabolites (GMMs) on 3D HCT116 spheroids is carried out using a high-throughput imaging approach. Dose-responses, IC50 , and long-term exposure are calculated for the most promising native (poly)phenols and GMMs. As a result, this research shows that (poly)phenol catabolites may play a key role in preventing cancer propagation. Indeed, µM concentration levels of (4R)-5-(3',4'-dihydroxyphenyl)-γ-valerolactone significantly decrease spheroid size at early stages of spheroid aggregation and gene expression of matrix metalloproteinases. A chronic exposure to (4R)-5-(3',4'-dihydroxyphenyl)-γ-valerolactone may lead to a reduced CRC risk. Daily intake of monomeric, oligomeric, and polymeric flavan-3-ols may increase the colonic concentrations of this metabolite, and, in turn, this compound may act locally interacting with intestinal epithelial cells, precancerous and cancer cells.


An ultrastructural study of primary granule subtypes in human neutrophils.
To investigate the heterogeneity of primary neutrophil granules, neutrophils in the bone marrow of 68 patients with hematologic and non-hematologic diseases were observed by electron microscopy. In addition to typical primary granules, 3 primary granule subtypes, i.e., parallel tubular granules (PTGs), fibrillar granules (FGs), and periodic lamellar granules (PLGs), were present in neutrophils. PTGs were found in only one case of chronic neutrophilic leukemia (CNL). On the other hand, FGs and PLGs were present in various cases at varying frequencies. Three subtype granules were seen preferentially in immature neutrophils. These subtypes were positive for myeloperoxidase, showing that they represent primary granules. In addition, hybrid PTG/FG granules, hybrid PTG/PLG granules, and hybrid FG/PLG granules were seen in the PTG-positive CNL case. This shows that a close association is present between PTGs, FGs, and PLGs.


Usefulness scale for patient information material (USE) - development and psychometric properties.
One economical way to inform patients about their illness and medical procedures is to provide written health information material. So far, a generic and psychometrically sound scale to evaluate cognitive, emotional, and behavioral aspects of the subjectively experienced usefulness of patient information material from the patient's perspective is lacking. The aim of our study was to develop and psychometrically test such a scale. The Usefulness Scale for Patient Information Material (USE) was developed using a multistep approach. Ultimately, three items for each subscale (cognitive, emotional, and behavioral) were selected under consideration of face validity, discrimination, difficulty, and item content. The final version of the USE was subjected to reliability analysis. Structural validity was tested using confirmatory factor analysis, and convergent and divergent validity were tested using correlation analysis. The criterion validity of the USE was tested in an experimental design. To this aim, patients were randomly allocated to one of two groups. One group received a full version of an information brochure on depression or chronic low back pain depending on the respective primary diagnosis. Patients in the second group received a reduced version with a lower design quality, smaller font size and less information. Patients were recruited in six hospitals in Germany. After reading the brochure, they were asked to fill in a questionnaire. Analyzable data were obtained from 120 questionnaires. The confirmatory factor analysis supported the structural validity of the scale. Reliability analysis of the total scale and its subscales showed Cronbach's α values between .84 and .94. Convergent and divergent validity were supported. Criterion validity was confirmed in the experimental condition. Significant differences between the groups receiving full and reduced information were found for the total score (p<.001) and its three subscales (cognitive p<.001, emotional p=.001, and behavioral p<.001), supporting criterion validity. We developed a generic scale to measure the subjective usefulness of written patient information material from a patient perspective. Our construct is defined in line with current theoretical models for the evaluation of written patient information material. The USE was shown to be a short, reliable and valid psychometric scale.


Narrative review of brivaracetam for genetic generalized epilepsies.
The licensed treatment options for genetic generalized epilepsies are limited although many patients with these conditions require chronic pharmacological management with antiseizure medications and there are no curative surgical treatment options. Brivaracetam is being studied as a new therapeutic option for genetic generalized epilepsies. In order to carry out a narrative review on the efficacy and safety of brivaracetam in genetic generalized epilepsies, a literature research was performed in Pubmed, EMBASE, Cochrane and Clinical Trials.gov databases. Promising results were found with doses ranging from 50 to 200 mg/day in terms of efficacy (with > 50% responder rates between 36 and 84%), tolerability, and short and long-term safety (24-57% drug-associated adverse effects), with most studies reporting adequate retention rates and an absence of serious adverse effects, in monotherapy or as adjuvant therapy, even in refractory epilepsies, special populations and in patients with previous use and/or therapeutic failure with levetiracetam. According to our review, brivaracetam is a valid treatment alternative in patients with genetic generalized epilepsies capable of improving patients' quality of life by reducing seizure frequency with minimal adverse effects.


Determining Optimal Mean Arterial Pressure After Cardiac Arrest: A Systematic Review.
The use of cerebral autoregulation monitoring to identify patient-specific optimal mean arterial pressure (MAPOPT) has emerged as a technique to augment cerebral oxygen delivery in post-cardiac arrest patients. Our systematic review aims to determine (a) the average MAPOPT in these patients, (b) the feasibility of identifying MAPOPT, (c) the brain tissue oxygenation levels when MAP is within proximity to the MAPOPT and (d) the relationship between neurological outcome and MAPOPT-targeted resuscitation strategies. We carried out this review in accordance with the PRISMA guidelines. We included all studies that used cerebral autoregulation to determine MAPOPT in adult patients (> 16 years old) who achieved return of spontaneous circulation (ROSC) following cardiac arrest. All studies had to include our primary outcome of MAPOPT. We excluded studies where the patients had any history of traumatic brain injury, ischemic stroke or intracranial hemorrhage. We identified six studies with 181 patients. There was wide variability in cerebral autoregulation monitoring methods, length of monitoring, calculation and reporting of MAPOPT. Amongst all studies, the median or mean MAPOPT was consistently above 65 mmHg (range 70-114 mmHg). Definitions of feasibility varied among studies and were difficult to summarize. Only one study noted that brain tissue oxygenation increased as patients' MAP approached MAPOPT. There was no consistent association between targeting MAPOPT and improved neurological outcome. There is considerable heterogeneity in MAPOPT due to differences in monitoring methods of autoregulation. Further research is needed to assess the clinical utility of MAPOPT-guided strategies on decreasing secondary injury and improving neurological outcomes after ROSC.


[Lipedema from the differential diagnostic and therapeutic viewpoint].
Lipedema is a hereditary disease concerning exclusively women. We discuss the characteristics of diagnosis as well as the differential diagnosis between lipedema and primary lymphedema. Therapy is effective if the lipedema resembles a lymphedema.


Rates of reduced cytochrome c-ferricyanide binding and electron transfer.
The oxidation of reduced cytochrome c by ferricyanide has been studied over a wide range of ferricyanide concentrations using a continuous-flow apparatus. The formation of a ferrocytochrome c-ferricyanide complex has been demonstrated and the binding and electron transfer processes separated to give both the oxidation electron transfer rate and the binding rate parameters. The electron transfer rate has been found to be 1.86 . 10(3) s-1 in H2O buffer and 1.36 . 10(3) s-1 in 2H2O demonstrating that a deuterium isotope effect of similar magnitude (R = 1.37) to that found in the cytochrome reactions in photosynthetic bacteria [18] is also found in the reaction studied here. The binding association rate parameters also show a similar deuterium isotope effect suggesting that water rotation may be involved in both the binding of ferricyanide to reduced cytochrome c and the subsequent oxidation electron transfer.


Laminin degradation by matrix metalloproteinase 9 promotes ketamine-induced neuronal apoptosis in the early developing rat retina.
During early development, laminin degradation contributes to the death of neurons. This study aims to investigate the role and regulation of laminin in ketamine-induced apoptosis. We performed terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) and immunohistochemical assays to investigate the roles of the non-integrin laminin receptor, matrix metalloproteinase 9 (MMP9) in ketamine-induced neuronal apoptosis. In situ zymography, Western blot, and immunofluorescence were used to explore the relationships between laminin, MMP9 activity, and Zn2+ . Experiments were performed using whole-mount retinas dissected from Sprague Dawley rats. The TUNEL and immunohistochemical assays indicated that ketamine-induced neuronal apoptosis in early developing rat retina. Blockade of non-integrin laminin receptor promoted ketamine-induced apoptosis, while non-integrin laminin receptor activation attenuated ketamine-induced apoptosis. Ketamine-induced laminin degradation, possibly by enhancing the activity of MMP9. MMP9 inhibition reduced ketamine-induced apoptosis by reducing laminin degradation. Downregulation of Zn2+ attenuated the increased MMP9 activity, laminin degradation caused by ketamine and significantly reduced ketamine-induced neuronal apoptosis. Laminin degradation by MMP9 promoted ketamine-induced neuronal apoptosis in early developing rat retina. The non-integrin laminin receptor may be a pathway involved in ketamine-induced apoptosis. Zn2+ downregulation may play a protective role against ketamine-induced neuronal apoptosis through inhibiting MMP9 activity.


Changing the way that I am: students experience of educational preparation for advanced nursing roles in the community.
The redesign of the healthcare workforce in the United Kingdom (UK) has resulted in the rapid introduction of more 'advanced' community nursing roles. This presents varying challenges for universities seeking to prepare practitioners for these roles. This paper reports on a qualitative study conducted at one university in England which sought to explore the educational experiences of students preparing for and engaging in advanced nursing roles. Data was collected through focus groups and semi-structured interviews. This study found that educational preparation for advanced nursing roles in the community is varied and complex and involved a number of claims, concerns and issues, captured in three themes: 1. Re-inventing roles; 2. Re-creating selves; and 3. Re-engaging with learning. The findings reveal how those in advanced roles work across occupational boundaries and manage conflicts, using differentiated and complex sources and forms of knowledge and skills. Learning occurs in non-linear ways and is a good example of expansive or sideways learning. There is a need for further research on the type of curriculum and methods to best support students preparing for these roles and further study on the impact on patient experience and outcomes.


Serum neurofilament light chain, contactin-1 and complement activation in anti-MAG IgM paraprotein-related peripheral neuropathy.
In anti-myelin-associated glycoprotein IgM paraprotein-related peripheral neuropathy (anti-MAG PN), there is a lack of reliable biomarkers to select patients eligible for therapy and for evaluating treatment effects, both in routine practice and in clinical trials. Neurofilament light chain (NfL) and contactin-1 (CNTN1) can serve as markers of axonal and paranodal damage. Complement activation is involved in the pathogenesis in anti-MAG PN. We, therefore, hypothesized that serum NfL, CNTN1, C3b/c and C4b/c may function as biomarkers of disease activity in anti-MAG PN. In this prospective cohort study, we included 24 treatment-naïve patients with anti-MAG PN (mean age 69 years, 57% male) that had IgM paraproteinemia, a high IgM MAG-antibody, and clinical diagnosis of anti-MAG PN by a neurologist specialized in peripheral nerve disorders. We measured serum NfL, CNTN1, C3b/c and C4b/c, reference values were based on healthy controls. As controls, 10 treatment-naïve patients with IgM Monoclonal gammopathy of undetermined significance (MGUS) or Waldenström's Macroglobulinemia (mean age 69 years, 60% male) without signs of neuropathy were included (non-PN). NfL, CNTN1 levels in serum were mostly normal in anti-MAG PN patients and comparable to non-PN patients. C3b/c and C4b/c levels were normal in anti-MAG PN patients. Our results do not support serum NfL, CNTN1, and C3b/c and C4b/c as potential biomarkers in anti-MAG PN, although we cannot exclude that subgroups or subtle abnormalities could be found in a much larger cohort with longitudinal follow-up.


Comparative analysis of the results of suspension-urethroplasty according to Marshall-Marchetti-Krantz and of urethrovesicopexy with adhesive.
A comparative analysis is presented of the results of adhesive urethrovesicopexy and the conventional suspension method according to Marshall, Marchetti and Krantz. It appears that the results are less favorable when compared to those mentioned in the literature, and no doubt attributable to the difficult differential diagnosis of stress and urge incontinence. The adhesive method supplies significantly less favorable results than the conventional method according to Marshall, Marchetti and Krantz.


HIV infection and HERV expression: a review.
The human genome contains multiple copies of retrovirus genomes known as endogenous retroviruses (ERVs) that have entered the germ-line at some point in evolution. Several of these proviruses have retained (partial) coding capacity, so that a number of viral proteins or even virus particles are expressed under various conditions. Human ERVs (HERVs) belong to the beta-, gamma-, or spuma- retrovirus groups. Endogenous delta- and lenti- viruses are notably absent in humans, although endogenous lentivirus genomes have been found in lower primates. Exogenous retroviruses that currently form a health threat to humans intriguingly belong to those absent groups. The best studied of the two infectious human retroviruses is the lentivirus human immunodeficiency virus (HIV) which has an overwhelming influence on its host by infecting cells of the immune system. One HIV-induced change is the induction of HERV transcription, often leading to induced HERV protein expression. This review will discuss the potential HIV-HERV interactions.Several studies have suggested that HERV proteins are unlikely to complement defective HIV virions, nor is HIV able to package HERV transcripts, probably due to low levels of sequence similarity. It is unclear whether the expression of HERVs has a negative, neutral, or positive influence on HIV-AIDS disease progression. A positive effect was recently reported by the specific expression of HERVs in chronically HIV-infected patients, which results in the presentation of HERV-derived peptides to CD8+ T-cells. These cytotoxic T-cells were not tolerant to HERV peptides, as would be expected for self-antigens, and consequently lysed the HIV-infected, HERV-presenting cells. This novel mechanism could control HIV replication and result in a low plasma viral load. The possibility of developing a vaccination strategy based on these HERV peptides will be discussed.


Staphylococcal protein A and enhancement of disc RAST sensitivity.
IgG has been suspected as an interesting factor in IgE-antigen specific RAST reaction. Such interference has been suggested by treatment of the patient's sera with staphylococcal protein A to reduce the concentration of IgG prior to carrying out the RAST measurements. This procedure includes incubation of killed staphylococcus organisms with patients' sera and noting the elevations in counts per minute of the RAST values to various antigens. This evaluation was carried out in 11 patients. It would appear that modification of "blocking" IgG antibody might increase RAST sensitivity.


Definition and severity grading of postoperative lymphatic leakage following inguinal lymph node dissection.
Lymphatic complications occur frequently after radical inguinal lymph node dissection (RILND). The incidence of lymphatic leakage varies considerably among different studies due to the lack of a consistent definition. The aim of the present study is to propose a standardized definition and grading of different types of lymphatic leakage after groin dissection. A bicentric retrospective analysis of 82 patients who had undergone RILND was conducted. A classification of postoperative lymphatic leakage was developed on the basis of the daily drainage output, any necessary postoperative interventions and reoperations, and any delay in adjuvant treatment. In the majority of cases, RILND was performed in patients with inguinal metastases of malignant melanoma (n = 71). Reinterventions were necessary in 15% of the patients and reoperations in 32%. A new classification of postoperative lymphatic leakage was developed. According to this definition, grade A lymphatic leakage (continued secretion of lymphatic fluid from the surgical drains without further complications) occurred in 13% of the patients, grade B lymphatic leakage (persistent drainage for more than 10 postoperative days or the occurrence of a seroma after the initial removal of the drain that requires an intervention) in 28%, and grade C lymphatic leakage (causing a reoperation or a subsequent conflict with medical measures) in 33%. The drainage volume on the second postoperative day was a suitable predictor for a complicated lymphatic leakage (grades B and C) with a cutoff of 110 ml. The proposed definition is clinically relevant, is easy to employ, and may serve as the definition of a standardized endpoint for the assessment of lymphatic morbidity after RILND in future studies.


Staging of cytoskeletal and beta-amyloid changes in human isocortex reveals biphasic synaptic protein response during progression of Alzheimer's disease.
We have examined the relationships between dementia, loss of synaptic proteins, changes in the cytoskeleton, and deposition of beta-amyloid plaques in the neocortex in a clinicopathologically staged epidemiological cohort using a combination of biochemical and morphometric techniques. We report that loss of synaptic proteins is a late-stage phenomenon, occurring only at Braak stages 5 and 6, or at moderate to severe clinical grades of dementia. Loss of synaptic proteins was seen only after the emergence of the full spectrum of tau and beta-amyloid pathology in the neocortex at stage 4, but not in the presence of beta-amyloid plaques alone. Contrary to previous studies, we report increases in the levels of synaptophysin, syntaxin, and SNAP-25 at stage 3 and of alpha-synuclein and MAP2 at stage 4. Minimal and mild clinical grades of dementia were associated with either unchanged or elevated levels of synaptic proteins in the neocortex. Progressive aggregation of paired helical filament (PHF)-tau protein could be detected biochemically from stage 2 onwards, and this was earliest change relative to the normal aging background defined by Braak stage 1 that we were able to detect in the neocortex. These results are consistent with the possibility that failure of axonal transport associated with early aggregation of tau protein elicits a transient adaptive synaptic response to partial de-afferentation that may be mediated by trophic factors. This early abnormality in cytoskeletal function may contribute directly to the earliest clinically detectable stages of dementia.


Co-exposure to molybdenum and cadmium evokes necroptosis and decreases apoptosis in duck myocardium.
Superfluous molybdenum (Mo) and cadmium (Cd) in the environment are detrimental to organisms through their accumulation. The NF-κB/TNF-α axis plays a vital part in regulating necroptosis and apoptosis. However, the impacts of Mo and/or Cd on myocardium injury in ducks and the function of NF-κB/TNF-α axis are not clear in the process. In this research, ducks exposed to different dosages of Mo and/or Cd were applied as the study object. The findings substantiated that the accumulation of Mo and/or Cd caused elements imbalance and necroptosis in myocardial tissue. As p-NF-κB/TNF-α expression up-regulated, RIPK1/RIPK3/p-MLKL expression significantly increased in all treatment groups, while the expression of c-caspase-8/3 markedly decreased. Moreover, apoptosis rate obviously decreased in Cd treated groups and clearly elevated in Mo group. Mitochondria-mediated apoptosis was activated by excessive Mo and inhibited by Mo + Cd, but Cd exposure alone had little effect on it. Collectively, our research confirmed that Mo and/or Cd evoked necroptosis via NF-κB/TNF-α axis, and decreased death receptor-mediated apoptosis in duck myocardium, the impacts of Mo and/or Cd on mitochondrial-mediated apoptosis were different. These results are significant for studying toxicology of Mo and/or Cd and preserving the ecosystem.


The value of yearly chest X-ray in patients with stage I breast cancer.
In 263 patients with stage I breast cancer, i.e. tumour less than 5 cm in diameter, no invasion of skin and deep fascia, and no involvement of axillary lymph nodes, X-rays of the chest were performed at 6, 12 months and yearly thereafter to the 6th year or until recurrence, another cancer was detected, the patient refused further follow-up or died. Among 1599 examinations, in only 0.25% (four patients) were unsuspected malignant changes observed. Due to this low cost/benefit ratio a fixed routine schedule of repeated chest X-rays in stage I cancer patients, otherwise apparently free of disease, is not justified.


The rheumatology workforce in the Arab countries: current status, challenges, opportunities, and future needs from an ArLAR cross-sectional survey.
The Arab League of Associations for Rheumatology (ArLAR) Research Group (ARCH) conducted this study to investigate the number of current practicing rheumatologists in the Arab countries, to estimate the projected number of rheumatologists in 10 years, and to evaluate the current workload, practice profile, consultation waiting time, and geographical mobilities of these rheumatologists. This cross-sectional survey study was conducted in 16 Arab countries in two parts. The first survey was addressed nominally to national societies to estimate the current and projected workforce. The second was an anonymous e-survey elaborated by the study steering committee on the Google Forms platform and distributed to Arab rheumatologists using social media, WhatsApp, and mass e-mails to evaluate their practice. The mean number of rheumatologists in Arab countries was 0.84 per 100,000 inhabitants (mean age 47.5 years, 55% females), ranging from 0.06 (Sudan) to 1.86 (Tunisia). The number of rheumatologists is expected to increase by 50% in 2032. Nevertheless, a 20% increase in population associated with an increase in demand is also expected. Data from 446 rheumatologists (mean age 43.9 years, 60.5% females) revealed that 72% worked full-time, and 53% were employed in the public sector only. The average waiting time for a rheumatology consultation was 19.9 days. Of 394 rheumatologists, 19% obtained their rheumatology diplomas from non-Arab countries, and 47% of Gulf rheumatologists were non-citizen physicians. Considering local demographic disparities, healthcare system differences, and geographical mobilities, national authorities are advised to implement effective intervention plans to optimize the rheumatology workforce.


Membrane plasma exchange in patients with metastatic cancer.
Seven patients suffering from metastatic cancer and all showing objectively measurable tumours were treated with eight sessions of membrane plasma exchange. No other oncological treatment was administered during the period of plasma exchange. The procedure itself was well tolerated and subjective improvement was reported by some patients. No objective tumour regression was observed. Immune complex-like material and inflammatory proteins were efficiently removed. In some patients a decrease in the number of T lymphocytes, due to relative depletion of T mu cells, was noted.


Suppressive effect of ulinastatin on plasma fibronectin depression after cardiac surgery.
Plasma fibronectin, an opsonic glycoprotein, is known to modulate the reticuloendothelial phagocytic clearance of nonbacterial and, possibly, bacterial particulates. The decreased plasma fibronectin levels seen after cardiac surgery have been considered to derive mainly from opsonic consumption. In the present study, we demonstrated that the administration of ulinastatin, a human urinary trypsin inhibitor, to patients after cardiac surgery not only inhibited the postoperative depression of plasma fibronectin levels, but also maintained the plasma fibronectin level within the normal range. This effect apparently resulted from the inhibitory activity of ulinastatin on the proteolytic enzymes released after operation. This result suggests that the decreased plasma fibronectin level noted after cardiac surgery may derive mostly from excessive proteolytic enzymes. Our observation also indicates that the prophylactic administration of ulinastatin to patients undergoing major operations will result in a favorably functional reticuloendothelial phagocytic system.


[Immunology of infection by Trichinella spiralis sensu stricto].
The different aspects of immune response to the nematode Trichinella are considered. The enteral and parenteral phases of infection are evaluated in detail as regards the contribution of different participants: cells (mast cells, lymphocytes, eosinophils, neutrophils, macrophages), antibodies, complement, inflammation mediators, interleukins etc. The genetic regulation of the immune response, the modulation of the immune system by the parasite and finally the situation as regards vaccination are discussed.


Focal adhesion kinase as an immunotherapeutic target.
Focal adhesion kinase (FAK) is a ubiquitously expressed non-receptor tyrosine kinase involved in cancer progression and metastasis that is found overexpressed in a large number of tumors such as breast, colon, prostate, melanoma, head and neck, lung and ovary. Thus, FAK could be an attractive tumor associated antigen (TAA) for developing immunotherapy against a broad type of malignancies. In this study, we determined whether predicted T cell epitopes from FAK would be able to induce anti-tumor immune cellular responses. To validate FAK as a TAA recognized by CD4 helper T lymphocytes (HTL), we have combined the use of predictive peptide/MHC class II binding algorithms with in vitro vaccination of CD4 T lymphocytes from healthy individuals and melanoma patients. Two synthetic peptides, FAK(143-157) and FAK(1,000-1,014), induced HTL responses that directly recognized FAK-expressing tumor cells and autologous dendritic cells pulsed with FAK-expressing tumor cell lysates in an HLA class II-restricted manner. Moreover, since the FAK peptides were recognized by melanoma patient's CD4 T cells, this is indicative that T cell precursors reactive with FAK already exist in peripheral blood of these patients. Our results provide evidence that FAK functions as a TAA and describe peptide epitopes that may be used for designing T cell-based immunotherapy for FAK-expressing cancers, which could be used in combination with newly developed FAK inhibitors.


Candida species contamination of preservation fluid-outcome of renal transplantation in 6 patients.
Fungal infections are a rare but important cause of morbidity and mortality in kidney transplantation. Fungal contamination of the kidney preservation fluid may, sometimes, be the cause of these infections. However, the clinical consequences of fungal contamination of this fluid are not completely understood and literature on this topic is controversial. The purpose of this study was to determine the incidence of preservation fluid contamination by fungi and its clinical consequences. From June 2010 to September 2011, a prospective cohort analysis was conducted at our center, enrolling all patients who received a renal allograft and whose perfusion fluid was analyzed for microbiology sterility. Patients with perfusion fluids positive for fungi were further studied: the patients' status was assessed during regular visits and data were recorded, including clinical characteristics, infections, graft function, immunosuppressive regimen and outcomes. Microbiologic, cultures of 70 kidney perfusion fluids using specific mycologic media, obtained from 74 cadaveric renal transplants (4 fluids were unsuitable for analysis), were evaluated. Six samples were positive for yeasts (8.6%), with 4 isolates of Candida albicans and 2 isolates of Candida glabrata. Four patients had no evidence of fungal infection during the follow-up period (median 321 days); conversely, 2 patients developed severe mycotic vascular complications leading to transplantectomy. Perfusion fluid contamination by fungi is an elusive situation that can lead either to an unremarkable clinical course or to graft loss life-threatening situations. Routine culture of kidney perfusion fluid is critical for prompt diagnosis and early implementation of appropriate treatment.


Estimating the bacterial lag time: which model, which precision?
The objective of this work was to explore the large number of bacterial growth models recently proposed in the field of predictive microbiology, concerning their capacity to give reliable estimates of the lag phase duration (lambda). We compared these models on the basis of their underlying biological explanations of the lag phenomenon, their mathematical formulation and their statistical fitting properties. Results show that a variety of biological interpretations of the lag phase exists, although different biological hypotheses sometimes converge to give identical mathematical equations. The fit of the different models provides relatively close lambda estimates, especially if we consider that the imprecision of the lambda estimates is generally larger than the differences between the models. In addition, the consistency of the lambda estimates closely depends on the quality of the dataset on which models were fitted.


Extent, trends, and determinants of controller/reliever balance in mild asthma: a 14-year population-based study.
The majority of patients with asthma have the mild form of the disease. Whether mild asthma patients receive appropriate asthma medications has not received much attention in the literature. We examined the trends in indicators of controller/reliever balance. Using administrative health databases of British Columbia, Canada (2000 to 2013), we created a population-based cohort of adolescents/adults with mild asthma using validated case definition algorithms. Each patient-year of follow-up was assessed based on two markers of inappropriate medication prescription: whether the ratio of controller medications (inhaled corticosteroids [ICS] and leukotriene receptor antagonists [LTRA]) to total asthma-related prescriptions was low (cut-off 0.5 according to previous validation studies), and whether short-acting beta agonists (SABA) were prescribed inappropriately according to previously published criteria that considers SABA in relation to ICS prescriptions. Generalized linear models were used to evaluate trends and to examine the association between patient-, disease-, and healthcare-related factors and medication use. The final cohort consisted of 195,941 mild asthma patients (59.5% female; mean age at entry 29.6 years) contributing 1.83 million patient-years. In 48.8% of patient-years, controller medications were suboptimally prescribed, while in 7.2%, SABAs were inappropriately prescribed. There was a modest year-over-year decline in inappropriate SABA prescription (relative change - 1.3%/year, P < 0.001) and controller-to-total-medications (relative change - 0.5%/year, P < 0.001). Among the studied factors, the indices of type and quality of healthcare (namely respirologist consultation and receiving pulmonary function test) had the strongest associations with improvement in controller/reliever balance. Large number of mild asthma patients continue to be exposed to suboptimal combinations of asthma medications, and it appears there are modifiable factors associated with such phenomenon.


Neuroleptic drug treatment alters in vitro central neurotensin metabolism.
Neurotensin (NT) has been shown to possess pharmacological properties associated with neuroleptic drugs. To determine if chronic haloperidol (HL; 3.5 mg/kg/day) or chlorpromazine (CPZ; 4.2 mg/kg/day) treatment affects central NT metabolism, HL and CPZ were perfused via Alzet minipumps into male Sprague-Dawley rats for 8 days. Purified synaptosomal plasma membrane (pSPM) were isolated and time-course incubated with NT (100 microM; 30-120 min). All samples were analyzed by high resolution, reversed-phase high performance liquid chromatography. HL and CPZ caused an increase in NT metabolism at the pSPM. Although an increase in NT metabolism would result in a loss of biological activity, it does lead to a significant accumulation of the biologically active NT fragment NT-(9-13), which has been shown to bind to the NT receptor. Therefore, neuroleptic drug treatment alters NT metabolism at the pSPM, leading to the formation of a fragment with antinociceptive activity.


Pulse contour techniques for perioperative hemodynamic monitoring: A nationwide carbon footprint and cost estimation.
The question of environmentally sustainable perioperative medicine represents a new challenge in an era of cost constraints and climate crisis. The French Society of Anaesthesia and Intensive Care (SFAR) recommends stroke volume optimization in high-risk surgical patients. Pulse contour techniques have become increasingly popular for stroke volume monitoring during surgery. Some require the use of specific disposable pressure transducers (DPTs), whereas others can be used with standard DPTs. Quantify and compare the carbon footprint and cost of pulse contour techniques using specific and standard DPTs on a yearly basis and at a national level. We estimated the number of high-risk surgical patients monitored every year in France with a pulse contour technique, and the plastic waste, carbon footprint and cost associated with the use of specific and standard DPTs. When compared to pulse contour techniques working with a standard DPT, techniques requiring a specific DPT are responsible for an increase in carbon dioxide emission estimated at 65-83 tons/yr and for additional hospital cost estimated at €67 million/yr. If, as recommended by the SFAR, all high-risk surgical patients were monitored, the difference would reach 179-227 tons/yr for the environmental impact and €187 million/yr for the economic impact. From an environmental and economic standpoint, pulse contour techniques working with standard DPTs should be recommended for the perioperative hemodynamic monitoring of high-risk surgical patients.


T- and B-Cells in the Inner Invasive Margin of Hepatocellular Carcinoma after Resection Associate with Favorable Prognosis.
In this retrospective study on 67 patients with hepatocellular carcinoma (HCC), after tumor resection, we evaluated the significance of CD3+ and CD8+ T-lymphocytes and CD20+ B-lymphocytes in tumor and non-tumor liver for time to recurrence (TTR), disease-free survival (DFS) and overall survival. After immunohistochemical staining, the density of nucleated lymphocyte profiles (QA) was estimated stereologically in the tumor center (TC), inner margin (inn M), outer margin (out M), peritumor and non-tumor liver. In TC, intermediate and high QA of CD8+ cells predicted longer TTR, whereas CD3+ and CD20+ were predictive only at high QA. DFS was predicted by high QA of CD3+, CD8+ and CD20+ cells in TC. The inn M harbored smaller QA of CD3+, CD8+ and CD20+ lymphocytes than out M. In contrast to out M, high T-cells' QA and intermediate and high B-cell QA in inn M predicted longer TTR and DFS. High inn M/out M QA ratios of CD3+ and CD20+ cells were associated with longer TTR and DFS, whereas high inn M/out M QA ratio of CD8+ was predictive only for DFS. Patients with intermediate-high QA of combined CD8+ and CD20+ cells in inn M showed longer TTR and DFS, compared to CD8+-high or CD20+-high alone. Our findings highlight overall heterogeneity of the tumor invasive margin, the importance of inn M, and the predictive role of B-cells.


Activation of extracellular signal-regulated kinase in the trigeminal ganglion following both treatment of the dura mater with capsaicin and cortical spreading depression.
Extracellular signal-regulated kinase (ERK) is known to be phosphorylated after exposure to noxious stimuli. In this study, we investigated the response in the dura mater to nociceptive stimulation, which is thought to be responsible for the pathogenesis of headaches, including migraines. We also examined the level of ERK phosphorylation in the trigeminal ganglion following cortical spreading depression (CSD), which is thought to play an important role in migraine pathophysiology. Western blot and immunohistochemical analyses showed a significant increase in the ERK phosphorylation levels 3 min following an application of 10mM capsaicin to the dura mater. This increase was inhibited after an application of the TRPV1 antagonist capsazepine or a MEK inhibitor. An immunohistochemical analysis revealed that most of the small-sized trigeminal ganglion neurons with TRPV1-immunoreactivity that innervate the dura mater exhibited pERK-immunoreactivity, suggesting that these neurons had responded to nociceptive stimulation. CSD increased the level of ERK phosphorylation 30 min after its elicitation, and this response was inhibited by a prior intraventricular administration of TRPV1 antagonist. These results indicate that CSD can activate dural TRPV1 to send nociceptive signals to the trigeminal system, and they provide important clues regarding the relationship between CSD and the trigeminovascular system.


A transient species of poly(A)+ RNA detected by a myosin heavy chain cDNA probe in muscle cell culture during terminal differentiation.
Primary cell cultures were prepared from breast muscles of 11 day 4 hour-embryonic chicks. Cytoplasmic RNAs were isolated from the cultured cells at various time intervals from day 3 to day 8. A [P32] DNA probe complementary to messenger RNA of myosin heavy chain was used to hybridize with the RNAs after gel electrophoresis. A transient species of polyadenylated RNA with a decreased mobility in electrophoresis was detected during a period of time when contractions of syncytial fibers were first observed.


Picture Good Health: A Church-Based Self-Management Intervention Among Latino Adults with Diabetes.
Churches may provide a familiar and accessible setting for chronic disease self-management education and social support for Latinos with diabetes. We assessed the impact of a multi-faceted church-based diabetes self-management intervention on diabetes outcomes among Latino adults. This was a community-based, randomized controlled, pilot study. One-hundred adults with self-reported diabetes from a Midwestern, urban, low-income Mexican-American neighborhood were included in the study. Intervention participants were enrolled in a church-based diabetes self-management program that included eight weekly group classes led by trained lay leaders. Enhanced usual care participants attended one 90-minute lecture on diabetes self-management at a local church. The primary outcome was change in glycosylated hemoglobin (A1C). Secondary outcomes included changes in low-density lipoproteins (LDL), blood pressure, weight, and diabetes self-care practices. Participants' mean age was 54 ± 12 years, 81 % were female, 98 % were Latino, and 51 % were uninsured. At 3 months, study participants in both arms decreased their A1C from baseline (-0.32 %, 95 % confidence interval [CI]: -0.62, -0.02 %). The difference in change in A1C, LDL, blood pressure and weight from baseline to 3-month and 6-month follow-up was not statistically significant between the intervention and enhanced usual care groups. Intervention participants reported fewer days of consuming high fat foods in the previous week (-1.34, 95 % CI: -2.22, -0.46) and more days of participating in exercise (1.58, 95 % CI: 0.24, 2.92) compared to enhanced usual care from baseline to 6 months. A pilot church-based diabetes self-management intervention did not reduce A1C, but resulted in decreased high fat food consumption and increased participation in exercise among low-income Latino adults with diabetes. Future church-based interventions may need to strengthen linkages to the healthcare system and provide continued support to participants to impact clinical outcomes.


Association of serum nitric oxide metabolite level with mortality in patients undergoing coronary angiography.
Nitric oxide (NO) is a relevant molecule for vascular homeostasis. The level of serum NO metabolites (NOx), which consist of nitrite and nitrate, has been investigated as an alternative biomarker of NO production, but its clinical value has not yet been determined. 143 patients (66 ± 12 years old) were followed up after coronary catheterization. During a median (inter-quartile range) observation period of 6.13 (3.32-9.21) years, there were 20 (14 %) all-cause deaths, including 11 (8 %) cardiovascular deaths, 17 (12 %) major adverse cardiovascular events, and 17 (12 %) hospital admissions for heart failure. Median NOx level was 34.5 μmol/L (23.9-54.3). NOx was a risk factor for all-cause death [hazard ratio (HR) by unit increase, 1.010, 95 % confidence interval (CI) 1.001-1.018; p = 0.021] and heart failure (HR 1.010, CI 1.001-1.019; p = 0.029). Even after adjustment for age, sex, coronary risk factors, C-reactive protein, log-transformed brain natriuretic peptide, estimated glomerular filtration rate, and nitrate treatment, NOx was a risk factor for all-cause death (HR 1.015, CI 1.004-1.027; p = 0.008) and admission with heart failure (HR 1.018, CI 1.005-1.018, p = 0.007). An increase in serum NOx level does not herald a benign clinical course but is an independent predictor of high risk of any-cause mortality and heart failure.


Characterization of a new 1,3-1,4-β-glucanase gene from Bacillus tequilensis CGX5-1.
1,3-1,4-β-Glucanase received great interest due to its application in brewing and feed industries. Application of 1,3-1,4-β-glucanase in brewing industry helps make up for the defect that plant-derived β-glucanases are heat-sensitive. A new strain, CGX5-1, exhibited remarkable 1,3-1,4-β-glucanase, was isolated from Asian giant hornet nest and identified Bacillus tequilensis. Moreover, a new 1,3-1,4-β-glucanase gene from B. tequilensis was cloned and measured to be 720 bp encoding 239 amino acids, with a predicted molecular weight of 26.9 kDa. After expressed in Escherichia coli BL21, active recombinant enzyme of 24 kDa was detected in the supernatant of cell culture, with the activity of 2,978.2 U/mL. The new enzyme was stable in the pH 5.0-7.5 with the highest activity measured at pH 6.0. Moreover, it is thermostable within 45 to 60 °C. The property of the new recombinant enzyme makes this enzyme a broad prospect in brewing industry. Moreover, this is the first report on 1,3-1,4-β-glucanase produced by B. tequilensis.


Insomnia in Patients With Chronic Kidney Disease.
Insomnia and poor self-perceived sleep are very common in patients with chronic kidney disease (CKD). Poor sleep is associated with fatigue, sleepiness, impaired daytime functioning, impaired health-related quality of life, and increased morbidity and mortality. Many illness- and treatment-related factors (metabolic changes, inflammation, altered sleep regulatory mechanisms, symptoms and complications of CKD, comorbid conditions, medications, and renal replacement therapies) may disturb sleep and contribute to the high prevalence of insomnia in this patient population. Accordingly, the approach to both diagnosing and treating this condition is quite complex. Although sleep-related problems are very important for patients with CKD, they largely are under-recognized and undertreated. Very few intervention trials provide an evidence base to support treatment decisions in this particular patient population. With this review we hope to increase awareness of insomnia among professionals involved in the management of patients with CKD and to provide guidance in recognizing and treating this important condition.


Patients with no preoperative back pain have the best outcome after lumbar disc herniation surgery.
Most patients with lumbar disc herniations requiring surgery have concomitant back pain. The purpose of the current study was to evaluate the outcome of surgery for lumbar disc herniations in patients with no preoperative back pain (NBP) compared to those reporting low back pain (LBP). 15,418 patients surgically treated due to LDH with primary discectomy from 1998 until 2020 were included in the study. Self-reported low back pain assessed with a numerical rating scale (NRS) was used to dichotomize the patients in two groups, patients without preoperative back pain (NBP, NRS = 0, n = 1333, 9%) and patients with preoperative low back pain (LBP, NRS > 0, n = 14,085, 91%). Patient reported outcome measures (PROMs) collected preoperatively and one-year postoperatively were used to evaluate differences in outcomes between the groups. At the one-year follow-up, 89% of the patients in the NBP group were completely pain free or much better compared with 76% in the LBP group. Significant improvement regarding leg pain was seen in all measured PROMs in both groups oneyear after surgery. In the NBP group, 13% reported clinically significant back pain (NRS difference greater than Minimally Clinical Important Difference (MICD)) at the one-year follow-up. Patients without preoperative back pain are good candidates for LDH surgery. 13% of patients without preoperative back pain develop clinically significant back pain one-year after surgery.


Oxalate digestibility in Neotoma albigula and Neotoma mexicana.
The cactus specialist, Neotoma albigula, tolerates high concentrations of potentially harmful oxalate compounds in its diet. Previous research has shown that oxalate compounds are broken down by intestinal micro-organisms. Thus the ability of N. albigula to utilize a diet high in oxalates may be a consequence of the adaptation of the microflora rather than its own evolution. To test this hypothesis, the oxalate degradation ability of N. albigula was compared with that of N. mexicana, a generalist herbivore. Apparent oxalate digestibility was not significantly different in the two species, when tested using field-acclimated individuals. Analysis of scats recovered from traps indicated that both species were consuming oxalates in the wild. I conclude that the ability of these herbivores to tolerate oxalates is a natural consequence of the utilization of microbial fermentation to degrade the structural carbohydrates of plants coupled with the high adaptive and evolutionary potential of the microflora.


Evaluation of intratumoral hemodynamics with color Doppler imaging in patients with colorectal carcinoma: comparison between waveform analysis and histopathologic characteristics.
We studied the relation between intratumoral hemodynamics and histopathologic characteristics in patients with colorectal carcinoma. A series of 82 patients with 28 well-differentiated adenocarcinomas, 40 moderately differentiated adenocarcinomas, 10 poorly differentiated adenocarcinomas, and 4 mucinous adenocarcinomas underwent color Doppler examination and surgical treatment. The waveform of blood flow in the thickened wall of the colon was analyzed by determining the maximum velocity (Vmax) and resistance index (RI). These parameters were compared with histopathologic findings of the resected specimens: gross form, tumor size, depth of invasion, histologic stage, and histopathologic classification. Both Vmax and RI were higher in the invasive tumors rather than the expansive ones. Vmax and tumor size were not correlated; however, the RI increased proportionately with tumor size in tumors larger than 4 cm in diameter. Both parameters increased with depth of invasion and histologic stage through stage IIIb. Both were markedly higher in mucinous adenocarcinomas than in the other histopathologic types. Furthermore, Vmax in well, moderately, and poorly differentiated adenocarcinomas did not differ significantly, although RI was negatively associated with the degree of differentiation. We concluded that blood-flow analysis is closely associated with histopathologic findings of colorectal carcinomas and that it provides information useful in the clinical management of these patients.


Ibandronate promotes autophagy by inhibiting Rac1-mTOR signaling pathway in vitro and in vivo.
We previously reported that ibandronate (IBAN) could improve endothelial function in spontaneously hypertensive rats. However, the mechanism by which IBAN improves endothelial function is unclear. The IBAN-induced autophagic process in vitro experiments were determined by detection of LC3, Beclin1, and P62 protein levels via western blotting. The autophagy flux was detected by confocal microscopy and transmission electron microscopy. For in vivo experiments, spontaneously hypertensive rats were orally administered with IBAN. Utilizing angiotensin II (Ang II) to stimulate the human umbilical vein endothelial cells (HUVECs) and human pulmonary microvascular endothelial cells (HPMECs) as a model of endothelial cell injury in hypertension, we found that IBAN promoted autophagy and protected cell viability in Ang II-treated-endothelial cells while these effects could be reversed by autophagy inhibitor. In terms of mechanism, IBAN treatment decreased the levels of Rac1 and mammalian target of rapamycin (mTOR) pathway. Activating either Rac1 or mTOR could reverse IBAN-induced autophagy. Furthermore, the in vivo experiments also indicated that IBAN promotes autophagy by downregulating Rac1-mTOR. Taken together, our results firstly revealed that IBAN enhances autophagy via inhibiting Rac1-mTOR signaling pathway, and thus alleviates Ang II-induced injury in endothelial cells.


Microsaccades are directed toward the midpoint between targets in a variably cued attention task.
Reliable, noninvasive biomarkers that reveal the internal state of a subject are an invaluable tool for neurological diagnoses. Small fixational eye movements, called microsaccades, are a candidate biomarker thought to reflect a subject's focus of attention [Z. M. Hafed, J. J. Clark, VisionRes. 42, 2533-2545 (2002); R. Engbert, R. Kliegl, VisionRes. 43, 1035-1045 (2003)]. The linkage between the direction of microsaccades and attention has mainly been demonstrated using explicit and unambiguous attentional cues. However, the natural world is seldom predictable and rarely provides unambiguous information. Thus, a useful biomarker must be robust to such changes in environmental statistics. To determine how well microsaccades reveal visual-spatial attention across behavioral contexts, we analyzed these fixational eye movements in monkeys performing a conventional change detection task. The task included two stimulus locations and variable cue validities across blocks of trials. Subjects were adept at the task, showing precise and graded modulations of visual attention for subtle target changes and performing better and faster when the cue was more reliable [J. P. Mayo, J. H. R. Maunsell, J. Neurosci. 36, 5353 (2016)]. However, over tens of thousands of microsaccades, we found no difference in microsaccade direction between cued locations when cue variability was high nor between hit and miss trials. Instead, microsaccades were made toward the midpoint of the two target locations, not toward individual targets. Our results suggest that the direction of microsaccades should be interpreted with caution and may not be a reliable measure of covert spatial attention in more complex viewing conditions.


Synthesis, crystal structure and thermal decomposition pathway of bis-(iso-seleno-cyanato-κN)tetra-kis-(pyridine-κN)manganese(II).
The reaction of MnCl2·2H2O with KSeCN and pyridine in water leads to the formation of the title complex, [Mn(NCSe)2(C5H5N)4], which is isotypic to its Fe, Co, Ni, Zn and Cd analogues. In its crystal structure, discrete complexes are observed that are located on centres of inversion. The Mn cations are octa-hedrally coordinated by four pyridine coligands and two seleno-cyanate anions that coordinate via the N atom to the metal centres to generate trans-MnN(s)2N(p)4 octa-hedra (s = seleno-cyanate and p = pyridine). In the extended structure, weak C-H⋯Se contacts are observed. Powder X-ray diffraction (PXRD) investigations prove that a pure sample was obtained and in the IR and Raman spectra, the C-N stretching vibrations are observed at 2058 and 2060 cm-1, respectively, in agreement with the terminal coordination of the seleno-cyanate anions. Thermogravimetric investigations reveal that the pyridine coligands are removed in two separate steps. In the first mass loss, a compound with the composition Mn(NCSe)2(C5H5N)2 is formed, whereas in the second mass loss, the remaining pyridine ligands are removed, which is superimposed with the decomposition of Mn(NCSe)2 formed after ligand removal. In the inter-mediate compound Mn(NCSe)2(C5H5N)2, the CN stretching vibration is observed at 2090 cm-1 in the Raman and at 2099 cm-1 in the IR spectra, indicating that the Mn cations are linked by μ-1,3-bridging anionic ligands. PXRD measurements show that a compound has formed that is of poor crystallinity. A comparison of the powder pattern with that calculated for the previously reported Cd(NCSe)2(C5H5N)2 indicates that these compounds are isotypic, which was proven by a Pawley fit.


Stereotactic radio surgery and radio frequency rhizotomy for trigeminal neuralgia in multiple sclerosis: A single institution experience.
For patients with medically unresponsive trigeminal neuralgia (TN), surgical options include micro vascular decompression (MVD), radiofrequency rhizotomy (RF), and stereotactic radio surgery (SRS). Multiple sclerosis (MS) is a demyelinating condition that can be associated with TN, but is not amenable to treatment with MVD. We sought to identify the outcome differences of patients with TN in MS undergoing SRS or RFR in an attempt to identify factors that may influence outcomes. We also evaluated cost outcomes, both initially and over time, based on the index procedure. We performed a retrospective review of our experience with 17 cases. A single institution retrospective chart review was performed. Since 1997, 17 patients with TN and MS have been treated at our institution. All patients underwent a preoperative MRI to rule out a compressive lesion. Patients either underwent SRS (n=7) or RFR (n=10) as their index procedure and were evaluated as a group based on this first procedure. Outcome measures included preoperative Expand Disability Status Score (EDSS) scores, pre- and postoperative facial pain and medication use, post-intervention facial numbness, need for subsequent procedures, and duration of follow-up. Charges for the index procedure, subsequent interventions, and total costs were tabulated and analyzed in 2017 US dollars, adjusting for inflation. The median age of patients at first operation in each group was 58.5±10.9 and 63.5±7.5 for SRS and RFR respectively. There were no significant differences in basic demographics. Overall, 71% of these patients had an excellent or good initial pain outcome. Over time, 60% of RFR and 29% of SRS patients required additional procedures to obtain satisfactory pain relief. The patients who underwent RFR as their index procedure required a significantly higher number of procedures to achieve adequate pain relief (RFR=2.7 vs SRS=2.0 [p=0.04]). The average index procedure costs in US dollars were significantly different (SRS=53,300±5257 vs RFR=12,315±3387). The average subsequent costs (costs incurred following the initial intervention) (SRS=8320±17,842, RFR=36,002±46,767) and total costs (SRS=61,620±16,087, RFR=48,317±48,475) were not statistically significantly different. TN in the setting of MS is highly difficult to treat medically with SRS and RFR being offered as options for these patients. Both can provide good initial pain relief. For patients who have RFR as their initial procedure, a larger number of procedures are required for relief compared to patients who initially underwent SRS. While there is a significant difference in the cost of the initial procedure, over time, with the cost of required subsequent interventions, there is no significant difference in total costs between the two groups.


Molecular cartography of leaf development - role of transcription factors.
Organ elaboration in plants occurs almost exclusively by an increase in cell number and size. Leaves, the planar lateral appendages of plants, are no exception. Forward and reverse genetic approaches have identified several genes whose role in leaf morphogenesis has been inferred from their primary effect on cell number and size, thereby distinguishing them as either promoters or inhibitors of cell proliferation and expansion. While such classification is useful in studying size control, a similar link between genes and shape generation is poorly understood. Computational modelling can provide a conceptual framework to re-evaluate the known genetic information and assign specific morphogenetic roles to the transcription factor-encoding genes. Here we discuss recent advances in our understanding of the roles of transcription factors in the planar growth of leaf lamina in two orthogonal dimensions.


OLD-TAVR score to predict 2-year mortality in patients aged 75 years and more undergoing transcatheter aortic valve replacement.
Decision-making on transcatheter aortic valve replacement (TAVR) in patients aged 75 years and older is complex. It could be facilitated by the identification of predictors of long-term mortality. This study aimed to identify predictors of 2-year mortality to develop a 2-year mortality risk score. Cohort study of consecutive patients aged ≥ 75 years who underwent TAVR after a comprehensive geriatric assessment (CGA) at our university hospital between 2012 and 2019. Predictors of 2-year mortality were determined using multivariable Cox regression. A point-based predictive model was developed based on risk factors and subsequently internally validated by fivefold cross-validation. The 345 patients (median age 87 years, 54% women) were fit/vulnerable (32%), mildly frail (37%), or moderately/severely frail (31%). The overall 2-year mortality rate was 26%, predicted by atrial fibrillation, hemoglobin ≤ 10 g/dL, age ≥ 87 years, BMI ≤ 24, eGFR ≤ 50 ml/min, and moderate/severe frailty. The risk score (range 0-12), named OLD-TAVR score, for 2-year mortality showed good discriminative power (AUC 0.70) and remained consistent after fivefold cross-validation (cvAUC 0.69). A risk score ≥ 8 (prevalence 20%) predicted a 45% (95%CI: 34-58%) two-year mortality, with high specificity (86%) and good positive predictive power (+ LR 2.43). A 2-year mortality risk score (OLD-TAVR score) for very old patients undergoing TAVR was developed based on six bio-clinical items. A score ≥ 8 identified patients in whom 2-year mortality was very high and thereby the TAVR futile. Study protocol B403, 26/09/2022, retrospectively registered.


Intravitreal ranibizumab for persistent diabetic vitreous haemorrhage: a randomised, double-masked, placebo-controlled feasibility study.
To determine the feasibility of a definitive study of intravitreal ranibizumab to promote the clearance of persistent diabetic vitreous haemorrhage and thereby avoid vitrectomy. This randomised, double-masked, placebo-controlled feasibility study recruited 24 participants with persistent diabetic vitreous haemorrhage listed for pars plana vitrectomy. Participants were randomised to a single 0.5-mg intravitreal ranibizumab injection or a single subconjunctival saline injection. The primary outcome measure was the number of participants requiring pars plana vitrectomy at week 7. Eight of 12 participants (66.7%) in the ranibizumab group required vitrectomy at week 7 versus 12 of 12 (100%) in the placebo group (absolute risk reduction 33.3%, 95% confidence interval 2.1-70.7%; p = 0.09). One additional eye in the ranibizumab group required vitrectomy by 12 months. Mean visual acuity letter score at 12 months was 72.7 ± 12.3 in the ranibizumab group and 75.1 ± 10.1 in the placebo group. Safety was similar across groups. Intravitreal ranibizumab may reduce the likelihood of proceeding to vitrectomy in patients with persistent, dense diabetic vitreous haemorrhage. Further studies appear feasible and justified.


Validation of left ventricular volume measurements by gated SPECT 99mTc-labeled sestamibi imaging.
Previous studies have shown that gated single photon emission computed tomography (SPECT) technetium 99-labeled sestamibi imaging provides accurate and reproducible measurement of left ventricular (LV) ejection fraction (EF), wall motion, and thickening. This study examined the reliability of gated SPECT sestamibi imaging in measuring LV end-diastolic volume (EDV), end-systolic volume (ESV), and stroke volume (SV). Gated SPECT measurements were compared with an independent nongeometric method based on thermodilution SV and first-pass radionuclide angiographic EF (using a multicrystal gamma camera). Twenty-four patients aged 58+/-11 years underwent cardiac catheterization and coronary angiography for evaluation of chest pain syndromes. None had primary valvular disease, intracardiac shunts, or atrial fibrillation. The correlation between the two methods were as follows: EDV: r = 0.89, P<.001; ESV: r = .938, P<.001; SV: r = 0.577, P<.001. Bland-Altman plots showed mean differences (+/-standard deviation [SD]) for EDV of -14.3+/-33.3 mL, for ESV of -0.4+/-23.7 mL, and for SV of -13.9+/-15.2 mL. The reproducibility of measuring EDV and ESV by gated SPECT was very high (r = 0.99 each). Gated 99mTc-labeled sestamibi SPECT provides reproducible LV volume measurements. With validation of volume measurement, gated SPECT provides comprehensive assessment of regional and global LV function. This information is important in many patient groups such as those with ischemic cardiomyopathy, concomitant coronary and valve disease, and those who have had myocardial infarction. It will also be useful to assess the incremental value of LV volumes in risk assessment.


Modification by metals, sulphydryl reagents and cyanide of the particle stimulated enhancement of oxygen consumption in bovine granulocytes.
A simple, rapid method for the isolation of neutrophil-enriched leucocyte suspensions from bovine blood is described. The capacity of these cells to produce a particle stimulated increase in oxygen consumption deteriorated during a period of storage of the cells whilst the viability of the cells remained unchanged. Potassium cyanide inhibited the basal oxygen consumption but enhanced the stimulated respiratory burst. Zinc ions also enhanced this respiratory burst but ferric and manganous ions did not. The lipid-soluble non-haem iron chelator, 4,4,4-trifluoro-1-(2 thienyl)-1,3-butanedione, preferentially inhibited the particle stimulated type of oxygen consumption, as did the sulphydryl reagents, N-ethyl maleimide and diazine dicarboxylic acid bis-dimethyl amide. These data allow us to consider that zinc ions may play a role in the respiratory burst associated with phagocytosis and that iron-sulphur interactions may be important in oxygen consuming reactions.


Can connectionist models of phonology assembly account for phonology?
Connectionist models have gained considerable success as accounts of how printed words are named. Their success challenges the view of grapheme-to-phoneme correspondences (GPCs) as rules. By extension, however, this challenge is sometimes interpreted also as evidence against linguistic rules and variables. This inference tacitly assumes that the generalizations inherent in reading (specifically, GPCs) are similar in their scope to linguistic generalizations and that they are each reducible to token associations. I examine this assumption by comparing the scope of generalizations required for mapping graphemes to phonemes and several linguistic phonological generalizations. Marcus (1998b) distinguishes between two types of generalizations: those that fall within a model's training space and those that exceed it. The scope of generalizations is determined by the model's representational choices--specifically, the implementation of operations over mental variables. An analysis of GPCs suggests that such generalizations do not appeal to variables; hence, they may not exceed the training space. Likewise, certain phonological regularities, such as syllable phonotactic constraints and place assimilation, may be captured by an associative process. In contrast, other phonological processes appeal to variables; hence, such generalizations potentially exceed the training space. I discuss one such case, the obligatory contour principle. I demonstrate that speakers conform to this constraint and that their behavior is inexplicable by the statistical structure of the language. This analysis suggests that, unlike GPCs, phonological generalizations may exceed the training space. Thus, despite their success in modeling GPCs, eliminative connectionist models of phonology assembly may be unable to provide a complete account for phonology. To the extent that reading is subject to phonological constraints, its modeling may require implementing operations over variables.


North Korean arrivals' medical service usage in South Korea, 2015-2019.
This study retrospectively reviews the medical service usage data of North Korean arrivals collected from 2015 to 2019. The purpose of this study is to understand the medical use status of North Korean arrivals and to design health policies for them. We reviewed 32,653 medical records of North Korean arrivals who visited the National Medical Center as outpatients and inpatients during a 5-year period. Among 1453 patients with an average age of 46.7 years, we found that among the treated patients, there were many women in their 40s and 50s who complained of psychiatric disorders. The most frequently visited department was psychiatry. The most frequently diagnosed disorder was unspecified depression. 88% of patients utilized Medical Care assistance type 1, which means that they are medical aid beneficiaries because they are usually in difficult economic circumstances. Medical examination and treatment fees of North Korean arrivals increased in general, and older patients paid more. Among North Korean arrivals, middle-aged women and mentally ill patients showed high medical needs. This study recommends that the government provide policy support to North Korean arrivals for professional psychiatric treatment and improvement of medical access. We also expect these results to be applied to the health problems of other refugees.


Traveling wave electroosmosis: the influence of electrode array geometry.
We used a mathematical model describing traveling-wave electroosmotic micropumps to explain their rather poor ability to work against pressure loads. The mathematical model is based upon the Poisson-Nernst-Planck-Navier-Stokes approach, that is, a direct numerical simulation, which allows a detail study of the energy transformations and the charging dynamics of the electric double layers. Using Matlab and COMSOL Multiphysics, we performed a set of extensive parametric studies to determine the dependence of generated electroosmotic flow on the geometric arrangement of the pump. The results suggest that the performance of AC electroosmotic pumps should improve with miniaturization. The AC electroosmosis is likely to be suitable only at submicrometer scale, as the pump's ability to work against pressure load diminishes rapidly when increasing the channel diameter.


Investigation of critical shear stress with simultaneous measurement of electrical impedance, capacitance and light backscattering.
Recent electrical investigation of hemorheology provided useful information on the kinetics of red blood cell (RBC) aggregation. However, because of the inconsistent results in the electrical measurements, we need to understand the electrical characteristics of RBC aggregation at various flow conditions. In the present study, AC electrical-capacitance (EC) and -impedance (EI) and light backscattering (LB) were simultaneously measured for transient shear-decreasing blood flow in a microchannel. EI, EC and LB signals of RBCs in plasma show similar time-varying curves, both yielding either a peak or a minimal point in the optimal frequency range (10~500 kHz). Critical shear stress (CSS) determined from EC showed the nearly same results as that determined from LB, with yielding hematocrits-independence and dextran-concentration dependence. However, the high concentration of fibrinogen caused electrical saturation, which resulted in different results of CSS determined from between LB and EC. These results suggest that electrical properties of RBC suspensions should be further examined to replace the optical method of measurement of RBC aggregation.


Comparison of Ti-35Nb-7Zr-5Ta and Ti-6Al-4V hydrofluoric acid/magnesium-doped surfaces obtained by anodizing.
Development of a new generation of stable β alloy, free of aluminum or vanadium and with better biological and mechanical compatibility and evaluate the surface properties of Ti-6Al-4V and Ti-35Nb-7Zr-5Ta after anodization in hydrofluoric acid, followed by deposition of different electrolyte concentrations of magnesium particles by micro arc-oxidation treatment. Disks were anodized in hydrofluoric acid. After this first anodization, the specimens received the deposition of magnesium using different concentration (8.5% and 12.5%) and times (30s and 60s). The surface morphology was assessed using scanning electron microscopy, and the chemical composition was assessed using energy dispersive x ray spectroscopy. The surface free energy was measured from the contact angle, and the mean roughness was measured using a digital profilometer. Anodization in hydrofluoric acid provided the formation of nanotubes in both alloys, and the best concentration of magnesium considered was 8.5%, as it was the condition where the magnesium was incorporated without covering the morphology of the nanotubes. X-ray dispersive energy spectroscopy showed magnesium incorporation in all conditions. The average roughness was increased in the Ti-35Nb-7Zr-5Ta alloy. It was concluded that anodizing could be used to deposit magnesium on the surfaces of Ti-6Al-4V and Ti-35Nb-7Zr-5Ta nanotubes, with better results obtained in samples with magnesium concentration in 8.5% and the process favored the roughness in the Ti-35Nb-7Zr-5Ta group.


Extraction of plasmid DNA using reactor scale alkaline lysis and selective precipitation for scalable transient transfection.
DNA extracted and purified for vaccination, gene therapy or transfection of cultured cells has to meet different criteria. We describe herein, a scalable process for the primary extraction of plasmid DNA suitable for transient expression of recombinant protein. We focus on the scale up of alkaline lysis for the extraction of plasmid DNA from Escherichia coli, and use a simple stirred tank reactor system to achieve this. By adding a series of three precipitations (including a selective precipitation step with ammonium acetate) we enrich very quickly the plasmid DNA content in the extract. The process has been thus far used to extract up to 100 mg of plasmid from 1.5 l of clarified lysate, corresponding to an E.coli bioreactor fermentation of 3 l.


Transport of malate and citrate into rat brain mitochondria under hypoxia and anesthesia.
Hypoxia and anesthesia inhibited penetration of malate and citrate into the brain mitochondria by 60% and 40%, respectively. Anesthetized animals exposed to low oxygen tension showed similar changes as those subjected to hypoxia without anesthesia. Recovery from anesthesia was rapid and the rates of citrate and malate uptake returned to the control values in approximately 60 min. In the case of hypoxia, days were required to restore the control values of citrate and malate uptake. Free fatty acids had no effect on the entry of malate and citrate into the mitochondria. However, changes in the levels of protein --SH groups were observed which may be responsible for the impaired transport of citrate and malate under hypoxic condition.


"Feeling fat," disgust, guilt, and shame: Preliminary evaluation of a mediation model of binge-eating in adults with higher-weight bodies.
"Feeling fat" is a subjective state that theoretically contributes to the maintenance of binge eating (BE). However, feeling fat, and its relation to BE among individuals with higher-weight bodies, has been infrequently studied. This study proposes a momentary-level model in which negative moral emotion states (disgust, guilt, shame) mediate the association between feeling fat and binge eating. In this study, 50 adults with higher-weight bodies (MBMI=40.3 ± 8.5 kg/m2; 84% female) completed a two-week ecological momentary assessment protocol, which measured experiences of feeling fat, emotion states, and binge-eating behavior. Univariate generalized linear mixed models (GLMM) evaluated the momentary associations among levels of feeling fat at Time 1, emotion states at Time 2, and binge eating at Time 2, controlling for Time 1 emotion states. GLMM results suggest that increases in each emotion from Time 1 to Time 2 mediated the association between Time 1 feeling fat and Time 2 binge eating. When modeled simultaneously within one multivariate multilevel structured equation model, disgust appeared to drive the relation between feeling fat and binge eating, over and above guilt and shame. Although preliminary, findings suggest increases in negative moral emotions, particularly disgust, mediate the feeling fat-binge eating association in adults with higher-weight bodies.


Conserved heterodimeric GTPase Rbg1/Tma46 promotes efficient translation in eukaryotic cells.
Conserved developmentally regulated guanosine triphosphate (GTP)-binding proteins (Drgs) and their binding partner Drg family regulatory proteins (Dfrps) are important for embryonic development, cellular growth control, differentiation, and proliferation. Here, we report that the yeast Drg1/Dfrp1 ortholog Rbg1/Tma46 facilitates translational initiation, elongation, and termination by suppressing prolonged ribosome pausing. Consistent with the genome-wide observations, deletion of Rbg1 exacerbates the growth defect resulting from translation stalling, and Rbg1 stabilizes mRNAs against no-go decay. Furthermore, we provide a cryoelectron microscopy (cryo-EM) structure of the 80S ribosome bound with Rbg1/Tma46 that reveals the molecular interactions responsible for Rbg1/Tma46 function. The Rbg1 subunit binds to the GTPase association center of the ribosome and the A-tRNA, and the N-terminal zinc finger domain of the Tma46 subunit binds to the 40S, establishing an interaction critical for the ribosomal association. Our results answer the fundamental question of how a paused ribosome resumes translation and show that Drg1/Dfrp1 play a critical role in ensuring orderly translation.


Cost-effectiveness of ribociclib for premenopausal or perimenopausal women with HR+/HER2- advanced breast cancer: a Brazilian public health care system perspective.
The MONALEESA-7 trial compared ribociclib plus endocrine therapy (ET) with placebo as first-line treatment of advanced luminal/HER2-negative breast cancer (ABC) in premenopausal and perimenopausal women (age <50 years) and showed significant benefits to progression-free survival and overall survival. This study aimed to compare the cost-effectiveness of ribociclib + ET versus ET alone in patients with ABC from the perspective of the Brazilian public national health system. We calculated the incremental cost-effectiveness ratio (ICER) using a Markov model with progression-free survival, post-progression survival, and death states. We expressed ICER as incremental costs per progression-free life-year (PFLY) and quality-adjusted life-year (QALY) gained in a 10-year time horizon. We used parametric survival distributions fit to MONALEESA-7 data to generate survival distributions for progression-free and post-progression survival. The largest British preference study in breast cancer served as the basis to estimate health-state utilities. We estimated direct costs (ABC treatment, follow-up, monitoring, and adverse events) using Brazilian-specific values from public sources. An expert consensus panel determined the resource patterns required. We applied annual discounts of 5% to costs and QALYs. Ribociclib + ET resulted in an incremental gain of 1.03 PFLYs and 0.80 QALYs at a cost of $37,319.31. The ICER of ribociclib + ET versus ET was $36,379.41 per PFLY gained and $46,590.79 per QALY gained. In deterministic sensitivity analysis, results were primarily affected by the annual discount rate, followed by the cost of ribociclib. In probabilistic sensitivity analysis, simulations agreed with the base-case. Ribociclib increased PFLYs and QALYs in patients with HR+/HER2- ABC when added to ET. Because Brazil does not have a formally defined cost-effectiveness threshold, other domains need to be considered for incorporation decisions, such as disease burden and humanistic impact on this young, economically active population. These findings may be useful in discussions for incorporation of ribociclib into the Brazilian public health system.


Imaginative ethics--bringing ethical praxis into sharper relief.
The empirical basis for this article is three years of experience with ethical rounds at Uppsala University Hospital. Three standard approaches of ethical reasoning are examined as potential explanations of what actually occurs during the ethical rounds. For reasons given, these are not found to be satisfying explanations. An approach called "imaginative ethics", is suggested as a more satisfactory account of this kind of ethical reasoning. The participants in the ethical rounds seem to draw on a kind of moral competence based on personal life experience and professional competence and experience. By listening to other perspectives and other experiences related to one particular patient story, the participants imagine alternative horizons of moral experience and explore a multitude of values related to clinical practice that might be at stake. In his systematic treatment of aesthetics in the Critique of Judgement, Kant made use of an operation of thought that, if applied to ethics, will enable us to be more sensitive to the particulars of each moral situation. Based on this reading of Kant, an account of imaginative ethics is developed in order to bring the ethical praxis of doctors and nurses into sharper relief. The Hebraic and the Hellenic traditions of imagination are used in order to illuminate some of the experiences of ethical rounds. In conclusion, it is argued that imaginative ethics and principle-based ethics should be seen as complementary in order to endow a moral discourse with ethical authority. Kantian ethics will do the job if it is remembered that Kant suggested only a modest, negative role of principle-based deliberation.


Ab initio alpha-alpha scattering.
Processes such as the scattering of alpha particles ((4)He), the triple-alpha reaction, and alpha capture play a major role in stellar nucleosynthesis. In particular, alpha capture on carbon determines the ratio of carbon to oxygen during helium burning, and affects subsequent carbon, neon, oxygen, and silicon burning stages. It also substantially affects models of thermonuclear type Ia supernovae, owing to carbon detonation in accreting carbon-oxygen white-dwarf stars. In these reactions, the accurate calculation of the elastic scattering of alpha particles and alpha-like nuclei--nuclei with even and equal numbers of protons and neutrons--is important for understanding background and resonant scattering contributions. First-principles calculations of processes involving alpha particles and alpha-like nuclei have so far been impractical, owing to the exponential growth of the number of computational operations with the number of particles. Here we describe an ab initio calculation of alpha-alpha scattering that uses lattice Monte Carlo simulations. We use lattice effective field theory to describe the low-energy interactions of protons and neutrons, and apply a technique called the 'adiabatic projection method' to reduce the eight-body system to a two-cluster system. We take advantage of the computational efficiency and the more favourable scaling with system size of auxiliary-field Monte Carlo simulations to compute an ab initio effective Hamiltonian for the two clusters. We find promising agreement between lattice results and experimental phase shifts for s-wave and d-wave scattering. The approximately quadratic scaling of computational operations with particle number suggests that it should be possible to compute alpha scattering and capture on carbon and oxygen in the near future. The methods described here can be applied to ultracold atomic few-body systems as well as to hadronic systems using lattice quantum chromodynamics to describe the interactions of quarks and gluons.


Digital subtraction angiography: intravenous and intra-arterial techniques.
As experience with digital subtraction angiography (DSA) increases, both its advantages and disadvantages have become more evident. Although the intravenous approach (IV-DSA) is safer and less expensive than conventional arteriography, images are frequently suboptimal. Good-quality IV-DSAs quite accurately detect hemodynamically significant lesions (sensitivity 92% and specificity 92%) but may overlook minor stenoses and wall irregularities (negative predictive value 69%). When fine detail is not required, IV-DSA may serve as the definitive radiographic examination. The intra-arterial approach (IA-DSA), which provides better images, uses less contrast medium, decreases the need for selective catheterization, and permits visualization of vessels in areas of sluggish flow, is being used more extensively. Careful consideration of the complementary roles of DSA, conventional arteriography, and noninvasive testing is necessary to provide accurate diagnostic information at the least hazard and expense to the patient.


A randomized trial of photocoagulation or injection sclerotherapy for the treatment of first- and second-degree hemorrhoids.
One hundred thirty-five patients with a diagnosis of hemorrhoids were randomized to receive either photocoagulation (P) (N = 73) or injection sclerotherapy with phenol (I) (N = 62). Each patient was assessed at one, four, and 12-month intervals after treatment. At one, four, and 12 months, there was no clinical difference between the groups; at 12 months, however, the proportion of patients who were symptomatically improved or asymptomatic was 59 percent after photocoagulation compared with 50 percent of those treated by injection (P = 73 percent; I = 50 percent). Seven patients treated by photocoagulation required repeated therapy compared with only one after injection (P less than 0.02). Additional therapy was used in eight patients after photocoagulation, as compared with three after injection. The operation rate for each group, however, was similar. There were no complications of therapy. Photocoagulation is an easy, non-invasive, safe method of treatment, giving results that are comparable to treatment by injection sclerotherapy.


Dopamine effects on pulmonary artery pressure in hypotensive preterm infants with patent ductus arteriosus.
We investigated the effects of dopamine on pulmonary artery pressure in 18 ventilated hypotensive preterm neonates by using the flow characteristics of the ductal shunt. Dopamine has variable effects on pulmonary/systemic mean arterial pressure ratio with half the neonates showing an increase in pulmonary pressure relative to systemic pressure.


[Functional morphology of stria vascularis after treatment with ethacrynic acid or atoxyl (author's transl)].
Surface alterations of the stria vascularis and Reissner's membrane were studied in guinea pigs following intravenous or intraperitoneal administration of ethacrynic acid or atoxyl. DC-potential was measured in the same animals during intoxication. In addition we studied changements in potassium concentration (perilymph, endolymph) of the atoxyl-treated animals.


Construction of a Brain-specific SLC23A2 Gene Knockout Mice Model.
Vitamin C (VC) is a key antioxidant of the Central Nervous System (CNS) and SLC23A2 (SVCT2) is the only transporter that actively transports VC into the brain. While the existing animal models of VC deficiency are in the whole body, the essential role of VC in brain development remains elusive. In our study presented here, the CRISPR/Cas9 technology was applied for the construction of a C57BL/6J-SLC23A2 em1(flox)Smoc mouse model, which was crossed with the Glial fibrillary acidic protein-driven Cre Recombinase (GFAP-Cre) genotype mice to generate a conditional knockout model of SLC23A2(SVCT2) gene in mice brain (GFAP-Cre;SLC23A2 flox/flox) after generations of crossbreeding. Our results showed that the expression of SVCT2 in GFAP-Cre;SLC23A2 flox/flox (Cre;svct2 f/f) mice brain was significantly decreased, and consistently, the expression of Neuronal nuclei antigen (NeuN), Glial fibrillary acidic protein (GFAP), calbindin-28k, brain-derived neurotrophic factor (BDNF) was down-regulated but Ionized calcium binding adapter molecule 1 (Iba-1) was up-regulated in Cre;svct2 f/f mice brain tissues. On the other hand, the levels of Glutathione, Reduced (GSH), myeloperoxidase (MDA), 8-isoprostane, tumor necrosis factor-α (TNF-α) and interleukin-6(IL-6) were significantly increased, but the levels of VC in brain tissue of the model group were decreased in Cre;svct2 f/f mice brain tissues, indicating the protective effect of VC against oxidative stress and inflammation during pregnancy. Thus, the conditional knockout of the SLC23A2 gene in the brain of mouse was successfully established by the CRISPR/Cas9 technology in our study, providing an effective animal model for studying the role of VC in fetal brain development.


Single-channel analysis of a ClC-2-like chloride conductance in cultured rat cortical astrocytes.
The single-channel behavior of the hyperpolarization-activated, ClC-2-like inwardly rectifying Cl- current (IClh), induced by long-term dibutyryl-cyclic-AMP-treated cultured cortical rat astrocytes, was analyzed with the patch-clamp technique. In outside-out patches in symmetrical 144 mM Cl-solutions, openings of hyperpolarization-activated small-conductance Cl channels revealed burst activity of two equidistant conductance levels of 3 and 6 pS. The unitary openings displayed slow activation kinetics. The probabilities of the closed and conducting states were consistent with a double-barrelled structure of the channel protein. These results suggest that the astrocytic ClC-2-like Cl- current Iclh is mediated by a small-conductance Cl channel, which has the same structural motif as the Cl- channel prototype CIC-0.


Efficacy and Safety of Asfotase Alfa in Infants and Young Children With Hypophosphatasia: A Phase 2 Open-Label Study.
Long-term data on enzyme replacement treatment of hypophosphatasia (HPP) are limited. To evaluate efficacy and safety of asfotase alfa in patients aged ≤5 years with HPP followed for up to 6 years. Phase 2 open-label study (July 2010 to September 2016). Twenty-two sites; 12 countries. Sixty-nine patients [median (range) age: 16.0 (0.02 to 72) months] with severe HPP and sign/symptom onset before age 6 months. Asfotase alfa 2 mg/kg three times/week or 1 mg/kg six times/week subcutaneously. Primary efficacy measure: Radiographic Global Impression of Change (RGI-C) score [-3 (severe worsening) to +3 (complete/near-complete healing)]. Additional outcome measures: respiratory status, growth, and safety. Post hoc analysis: characteristics of radiographic responders vs nonresponders at Year 1 (RGI-C: ≥+2 vs <+2). During median (minimum, maximum) 2.3 (0.02, 5.8) years of treatment, RGI-C scores improved significantly at Month 6 [+2.0 (-1.7, +3.0)], Year 1 [+2.0 (-2.3, +3.0)], and Last Assessment [+2.3 (-2.7, +3.0); P < 0.0001 all]. Of 24 patients requiring respiratory support at Baseline, 11 (46%) no longer needed support. Height/weight z scores generally increased. Nine patients died (13%). All patients experienced at least one adverse event; pyrexia was most common. Compared with responders [n = 50 (72%)], nonresponders [n = 19 (28%)] had more severe disease at Baseline and a higher rate of neutralizing antibodies (NAbs) at Last Assessment. Most infants/young children given asfotase alfa showed early radiographic and clinical improvement sustained up to 6 years; radiographic nonresponders had more severe disease and more frequent NAbs at Last Assessment.


Genetic engineering of a temperate phage-based delivery system for CRISPR/Cas9 antimicrobials against Staphylococcus aureus.
Discovery of clustered, regularly interspaced, short palindromic repeats and the Cas9 RNA-guided nuclease (CRISPR/Cas9) system provides a new opportunity to create programmable gene-specific antimicrobials that are far less likely to drive resistance than conventional antibiotics. However, the practical therapeutic use of CRISPR/Cas9 is still questionable due to current shortcomings in phage-based delivery systems such as inefficient delivery, narrow host range, and potential transfer of virulence genes by generalized transduction. In this study, we demonstrate genetic engineering strategies to overcome these shortcomings by integrating CRISPR/Cas9 system into a temperate phage genome, removing major virulence genes from the host chromosome, and expanding host specificity of the phage by complementing tail fiber protein. This significantly improved the efficacy and safety of CRISPR/Cas9 antimicrobials to therapeutic levels in both in vitro and in vivo assays. The genetic engineering tools and resources established in this study are expected to provide an efficacious and safe CRISPR/Cas9 antimicrobial, broadly applicable to Staphylococcus aureus.