Intelligent checklists improve checklist compliance in the intensive care unit: a prospective before-and-after mixed-method study.
We examined whether a context and process-sensitive 'intelligent' checklist increases compliance with best practice compared with a paper checklist during intensive care ward rounds. We conducted a single-centre prospective before-and-after mixed-method trial in a 35 bed medical and surgical ICU. Daily ICU ward rounds were observed during two periods of 8 weeks. We compared paper checklists (control) with a dynamic (digital) clinical checklist (DCC, intervention). The primary outcome was compliance with best clinical practice, measured as the percentages of checked items and unchecked critical items. Secondary outcomes included ICU stay and the usability of digital checklists. Data are presented as median (interquartile range). Clinical characteristics and severity of critical illness were similar during both control and intervention periods of study. A total of 36 clinicians visited 197 patients during 352 ward rounds using the paper checklist, compared with 211 patients during 366 ward rounds using the DCC. Per ICU round, a median of 100% of items (94.4-100.0) were completed by DCC, compared with 75.1% (66.7-86.4) by paper checklist (P=0.03). No critical items remained unchecked by the DCC, compared with 15.4% (8.3-27.3) by the paper checklist (P=0.01). The DCC was associated with reduced ICU stay (1 day [1-3]), compared with the paper checklist (2 days [1-4]; P=0.05). Usability of the DCC was judged by clinicians to require further improvement. A digital checklist improved compliance with best clinical practice, compared with a paper checklist, during ward rounds on a mixed ICU. NCT03599856.


Nascent membrane and secretory proteins differ in FRET-detected folding far inside the ribosome and in their exposure to ribosomal proteins.
Fluorescence resonance energy transfer measurements reveal that a transmembrane sequence within a nascent membrane protein folds into a compact conformation near the peptidyltransferase center and remains folded as the sequence moves through a membrane bound ribosome into the translocon. This compact conformation is compatible with an alpha helix because nearly the same energy transfer efficiency was observed when the transmembrane sequence was integrated into the lipid bilayer. Since the transmembrane sequence unfolds upon emerging from a free ribosome, this nascent chain folding is ribosome induced and stabilized. In contrast, a nascent secretory protein is in an extended conformation in the exit tunnel. Furthermore, two ribosomal proteins photo-crosslink to nascent membrane but not secretory proteins. These interactions coincide with the previously described sequential closing and opening of the two ends of the aqueous translocon pore, thereby suggesting that ribosomal recognition of nascent chain folding controls the operational mode of the translocon at the ER membrane.


MyD88 Deficiency, but Not Gut Microbiota Depletion, Is Sufficient to Modulate the Blood-Brain Barrier Function in the Mediobasal Hypothalamus.
Circumventricular organs (CVOs), including the mediobasal hypothalamus (MBH), have an incomplete blood-brain barrier (BBB). In this study, we determined if the BBB function in the MBH is modulated by the gut microbiota or by the Toll-like receptor (TLR) adapter proteins TRIF or MyD88 signaling. By injecting mice with Evans blue, a marker for BBB permeability, we show that germ-free (GF) and conventionally raised (CONV-R) mice did not differ in the number of Evans blue-positive cells in MBH. Acute modulation of the gut microbiota did not change the number of Evans blue-positive cells. In contrast, CONV-R Myd88-/- and Trif-/- mice had a reduced number of cells in direct contact to the circulation compared to wildtype (WT) mice. This was accompanied by increased tight junction proteins in the blood vessels in Myd88-/- mice. To further characterize the BBB function, we injected WT and Myd88 -/- CONV-R mice as well as WT GF mice with monosodium glutamate (MSG), a neurotoxin that does not cross the BBB. While MSG caused vast cell death in the MBH in CONV-R and GF WT mice, Myd88 -/- mice were protected from such cell death suggesting that fewer cells are exposed to the neurotoxin in the Myd88 -/- mice. Taken together, our results suggest that MyD88 deficiency, but not gut microbiota depletion, is sufficient to modulate the BBB function in the MBH.


Interparticle and Brownian forces controlling particle aggregation and rheology of silicate melts containing platinum-group element particles.
We study the rheology of silicate melts containing platinum-group element (PGE) particles. They exhibit a shear-thinning behaviour, an intense aggregation tendency, and an anomalously high apparent viscosity in the low shear rate limit, even at very low particle volume fraction. Using a compilation of published experimental data, we analyse these effects in three steps. Firstly, we observe that the viscosities of these suspensions are much higher than those of natural silicate crystal-bearing melts for low shear rate regimes. Secondly, we demonstrate that the viscosities at low shear rate limit cannot be estimated by classical rheological models but rather may be understood as the result of particle aggregation, trapping dead fluid, and thereby increasing the effective particle volume fraction. Finally, we scale the critical shear rates for shear-thinning using a Peclet number analysis-invoking a competition between random thermal particle motion and hydrodynamic shearing motion-and, using an empirical extension, we additionally account for the particle-particle interaction energetics. We propose a framework in which the rheology of this family of particle-bearing melts can be predicted, and demonstrate that at low Peclet numbers, PGE-bearing particle aggregation is driven by interparticle forces and Brownian motion.


Clerodane furanoditerpenoids as the probable cause of toxic hepatitis induced by Tinospora crispa.
Tinospora crispa is a popular traditional herbal plant commonly used throughout the world for treatment of various diseases, in particular type 2 diabetes mellitus. We report here a new case of toxic hepatitis in a 57-year old male patient in the French West Indies following the consumption of two aqueous extracts of fresh Tinospora crispa stems. It thus differs from two previously reported cases that concerned the chronic intake of powdered dry stems delivered in solid oral dosage forms (i.e. pellets and tablets). Liquid Chromatography-Diode Array Detection-Mass Spectrometry (LC/DAD/MS) analyses were performed on an aqueous extract of the offending sample that mimics the swallowed preparation. They revealed the presence of species-specific molecular marker borapetoside C (1) and thus enabled an unambiguous phytochemical identification. The exploration of tandem MS/MS data obtained by ultra-high performance liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-HRMS) allowed the identification of 17 additional cis-clerodane-type furanoditerpenoid lactones, analogues of 1. These results support the hypothesis that the mechanisms underlying hepatotoxicity of Tinospora crispa are the same as those encountered with furanoditerpenoids-containing plants such as Teucrium chamaedrys or Dioscorea bulbifera. In the context of type 2 diabetes treatment, we recommend that Tinospora crispa intake should be more closely monitored for signs of hepatotoxicity.


Photodynamic therapy for central-type early-stage lung cancer.
Photodynamic therapy has been considered as the first choice of treatment for central-type early-stage lung cancer. Recent advances in the comprehensive diagnosis of central-type early-stage lung cancer and the selection of a good indication for photodynamic therapy have been anticipated to improve the therapeutic outcome of this type of early-stage lung cancer. In terms of enrollment, evaluation of the tumor area on the bronchial surface and the depth of invasion in the bronchial wall is important. Autofluorescence bronchoscopy and endobronchial ultrasonography have shown considerable impact on diagnostic bronchoscopy for this type of lung cancer. In terms of size, central-type early-stage lung cancer of < 1 cm diameter has shown a favorable cure rate by photodynamic therapy. The development of photodynamic therapy with a new photosensitizer is expected to further expand its indications to encompass even large tumors of > 1.0 cm diameter owing to its stronger effect. We postulate that the indication of photodynamic therapy will expand to larger central tumors together with a possible therapeutic option for peripheral early cancer.


Neoadjuvant Chemotherapy Followed by Cystectomy: a Single-Center Experience.
Nearly 50% of patients with muscle-invasive bladder cancer treated with cystectomy alone will progress to metastatic disease. Surgery alone is not a sufficient therapy in a large number of patients with invasive bladder cancer. Systemic therapy with cisplatin-based chemotherapy has been shown to provide response rates in several bladder cancer studies. There have been multiple randomized controlled studies undertaken to define further the effectiveness of neoadjuvant cisplatin-based chemotherapy in advance of cystectomy. In this study, we have retrospectively reviewed our series of patients who underwent neoadjuvant chemotherapy followed by radical cystectomy for muscle-invasive disease. Between Jan 2005 and Dec 2019, 72 patients underwent radical cystectomy following neoadjuvant chemotherapy over a 15-year period. The data was retrospectively collected and analyzed. The median age was 59.84 ± 8.967 years (range, 43 to 74), and the ratio of male to female patients was 5:1. Of the 72 patients, 14 (19.44%) completed all the three cycles, 52 (72.22%) completed at least two cycles, and the remaining 6 (8.33%) completed only one cycle of neoadjuvant chemotherapy. A total of 36 (50%) patients died during the follow-up period. The mean and median survival of the patients was 84.85 ± 4.25 months and 91.0 ± 5.83 months respectively. Neoadjuvant MVAC should be offered to patients with locally advanced bladder cancer and who are candidates for radical cystectomy. It is safe and effective in patients with adequate renal function. The patients need to be carefully monitored for chemotherapy-induced toxic effects, and appropriate intervention is necessary in the event of severe adverse effects.


A unique analytical solution of the white matter standard model using linear and planar encodings.
It is known that white matter modeling based on commonly used linear diffusion encoding is an ill-posed problem. We analyze the additional information gained from a double pulsed diffusion encoding. Zeroth (spherical means) and second-order (harmonic powers) rotation invariant signal features are used to factor micro- and mesoscopic contributions. The b-value dependency up to second-order of the features form 6 nonlinear equations, which are analyzed. The 6 derived equations can be uniquely solved for all relevant biophysical parameters. No assumptions about the form of the mesoscopic contribution (fiber dispersion) is necessary. Under certain conditions the solution still shows a certain degeneracy which is inherent to model. It is further shown that a combination of second-order information from single and spherical diffusion encoding is not enough to solve the problem. A combination of single and double pulsed diffusion encodings is sufficient to solve the full 3 compartment white matter model uniquely.


Embolization treatment of bleeding complications in pancreatitis.
Pseudoaneurysm following chronic pancreatitis is a severe complication that can lead to massive gastrointestinal bleeding. Surgical treatment means high risk for the patient. We report on two patients in whom the bleeding was managed by percutaneous transvascular embolization, a relatively non-invasive and successful method with low risk. The goal was either the definitive arrest of bleeding or stabilization of the patient to enable a surgical procedure. Embolization coils are the material most utilized for vessel occlusion. In patients with bleeding complication following pancreatitis, if sonography or computed tomography demonstrates a pseudoaneurysm, we recommend angiographic visualization and immediate subsequent embolization.


The impact of technology on the quality of health care.
Laser technology, developments in three-dimensional imaging, genetic engineering, and biosynthetic materials, and other technologies can promote quality care if they are used appropriately and correctly, are accessible to physicians and patients, and are shown to lead to successful outcomes. Formal organizational linkages and networks will enable providers to specialize in different technology and equipment yet still assure access for their patients to a full continuum of health care services. Advances in technology should have a significant, positive impact on the quality of care, yet with continued escalations in cost. Technology-based cost increases can be minimized with a renewed focus on early detection of diseases and on preventive strategies, efforts to ensure appropriate and cost-effective use of technology, greater selectivity in the use of "halfway" technologies, and increased incentives for healthy life-styles.


An experimental in-vivo canine model for adult shunt infection.
Detailed human studies of the mechanisms and development of shunt infection in real time are not possible, and we have developed a canine hydrocephalus model to overcome this. The intention of this pilot study was to show that the canine hydrocephalus model could be shunted using conventional "human" shunts, and that a shunt infection could be established so that further studies could then be planned. Hydrocephalus was induced in seven dogs (Canis familiaris) by fourth ventricle obstruction. Four weeks later they were shunted using a Hakim Precision valve. Four of the dogs received shunts whose ventricular catheter had been inoculated with Staphylococcus epidermidis, and three were uninoculated controls. Four weeks after shunting the dogs were sacrificed and necropsy was performed. Removed shunts and tissue samples were examined microbiologically and isolates were subjected to detailed identification and genomic comparison. All the dogs remained well after shunting. Examination of removed shunt components revealed S. epidermidis in the brain and throughout the shunt system in the four inoculated animals, but in two of these Staphylococcus intermedius was also found. S. intermedius was also isolated from all three "negative" controls. There were slight differences between S. intermedius strains suggesting endogenous infection rather than cross- infection from a point source. Shunt infection was established in the canine model, and had the experiment been extended beyond four weeks the typical microbiological, pathological and clinical features might have appeared. The occurrence of unplanned shunt infections in control animals due to canine normal skin flora reflects human clinical experience and underlines the usual source of bacteria causing shunt infection.


Serra da Estrela cheese's free amino acids profiles by UPLC-DAD-MS/MS and their application for cheese origin assessment.
Serra da Estrela cheese is a high-value Portuguese Protected Designation of Origin cheese, produced with raw ewe milk. Thus, information regarding its composition is of utmost relevance for both consumers and certified producers. In this work, the chromatographic profiles of free amino acids in cheeses (45 days of maturation, 6 producers located in 5 municipalities and produced from November 2017 to March 2018) were established by UPLC-DAD-MS/MS. The proposed method allowed detecting 19 free amino acids and cystine with overall limits of detection and quantification lower than 44 μmol/L (1.4 mg/100 g cheese, wet matter) and than 134 μmol/L (4.2 mg/100 g cheese, wet matter), respectively. In all cheeses, 17 free amino acids were quantified including 8 essential amino acids (histidine, leucine-isoleucine, lysine, methionine, phenylalanine, threonine, tryptophan and valine) and 9 non-essential amino acids (arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, proline, serine and tyrosine). The amounts of the free amino acids, essential free amino acids, branched chain free amino acids (leucine, isoleucine and valine) plus the free amino acids ratios (mg/g protein) were further used to identify the producer of Serra da Estrela cheeses. Linear discriminant analysis coupled with the simulated annealing variable selection algorithm was used allowing the correct classification of 96% and 90 ± 8% of the samples, for leave-one-out and repeated K-fold cross-validation procedures, respectively. The satisfactory predictive performance pointed out the possibility of using cheeses' amino acids profiles as origin biomarkers for authenticity control, warranting the correctness identification of the cheese producer/brand, which is quite relevant for ensuring the consumer confidence and satisfaction when purchasing this high-value dairy food.


Rickettsia conorii isolated from Rhipicephalus sanguineus introduced into Switzerland on a pet dog.
A tick/rickettsial survey in a household near Geneva, Switzerland, revealed that 30 (40%) of 75 nymphs and adults of the brown dog tick, Rhipicephalus sanguineus, were infected with a rickettsial agent biologically and antigenically indistinguishable from R. conorii, the causative agent of boutonneuse fever. Introduced in 1979 from either southern France or Italy by the family's pet dog, the tick infestation had steadily increased until 1981 when control measures were initiated. During 1980 and 1981, four persons associated with the household's pet dog contracted a febrile illness diagnosed as boutonneuse fever.


Anterior olfactory organ removal produces anxiety-like behavior and increases spontaneous neuronal firing rate in basal amygdala.
Some chemical cues may produce signs of anxiety and fear mediated by amygdala nuclei, but unknown is the role of two anterior olfactory epithelial organs, the septal and vomeronasal organs (SO-VNOs). The effects of SO-VNO removal were explored in different groups of Wistar rats using two complementary approaches: (i) the assessment of neuronal firing rate in basal and medial amygdala nuclei and (ii) behavioral testing. Fourteen days after SO-VNO removal, spontaneous activity in basal and medial amygdala nuclei in one group was determined using single-unit extracellular recordings. A separate group of rats was tested in the elevated plus maze, social interaction test, and open field test. Compared with sham-operated and intact control rats, SO-VNO removal produced a higher neuronal firing rate in the basal amygdala but not medial amygdala. In the behavioral tests, SO-VNO removal increased signs of anxiety in the elevated plus maze, did not alter locomotion, and increased self-directed behavior, reflecting anxiety-like behavior. Histological analysis showed neuronal destruction in the accessory olfactory bulb but not anterior olfactory nucleus in the SO-VNO group. The present results suggest the participation of SO-VNO/accessory olfactory bulb/basal amygdala relationships in the regulation of anxiety through a process of disinhibition.


Photomodulation alleviates cellular senescence of aging adipose-derived stem cells.
Mesenchymal stem cells (MSCs) therapies are emerging as a promising approach to therapeutic regeneration. Therapeutic persistence and reduced functional stem cells following cell delivery remain critical hurdles for clinical investigation due to the senescence of freshly isolated cells and extensive in-vitro passage. Cultured adipose-derived stem cells (ASCs) were derived from subcutaneous white adipose tissue isolated from mice fed a normal diet. We performed senescence-associated-β-galactosidase (SA-β-gal) staining, real-time PCR, and Westernblot to evaluate the levels related to cellular senescence markers. The mRNA expression levels of senescence markers were significantly increased in the later passage of ASCs. We show that light activation reduced the expression of senescent genes, and SA-β-Gal in all cells at passages. Moreover, the light-activated ASCs-derived exosomes decrease the expression of senescence, and SA-β-Gal in the later passage cells. We further investigated the photoreceptive effect of Opsin3 (Opn3) in light-activated ASCs. Deletion of Opn3 abolished the differences of light activation in reduced expression of senescent genes, increased Ca 2+ influx, and cAMP levels. ASCs can undergo cellular senescence in-vitro passage. Photomodulation might be better preserved over senescence and Opn3-dependent activation in aged ASCs. Light-activated ASCs-derived exosomes could be served as e a new protective paradigm for cellular senescence in-vitro passage. Video Abstract.


Association between psychological measures and brain natriuretic peptide in heart failure patients.
Brain natriuretic peptide (BNP) is a promising marker for heart failure diagnosis and prognosis. Although psychological factors also influence heart failure (HF) prognosis, this might be attributed to confounding by BNP. Our aim was to examine the association between multiple psychological markers using a prospective study design with repeated N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurements. The sample comprised 94 outpatients with systolic HF (80% men; mean age =62.2 ± 9.3). The psychological markers (i.e., anxiety, depression, and Type D personality), assessed with the Hospital Anxiety and Depression Scale (HADS), the Beck Depression Inventory (BDI), and the Type D Scale (DS14) were assessed only at baseline. Plasma NT-proBNP levels were measured at baseline and at 9 months. The prevalence of anxiety, depression, and Type D personality at baseline was 23.4% (HADS-A), 17.0% (HADS-D), 46.6% (BDI), and 21.3% (DS14), respectively. At baseline, none of the psychological risk markers were associated with NT-proBNP levels (all p >.05). In the subset of patients with scores on psychological risk markers both at baseline and at 9 months, there were no association between anxiety (p =0.44), depression (HADS-D: p =0.90; BDI: p =0.85), and Type D (p =0.63) with NT-proBNP levels using ANOVA for repeated measures. Our findings indicate that measures frequently used in HF to assess psychological risk markers are unconfounded by NT-proBNP. Futher studies are warranted to replicate these findings and examine whether psychological risk markers are independent predictors of prognosis in HF or an artifact that may be attributed to other biological or behavioral mechanisms.


Surgical treatment for secondary aortoesophageal fistula.
Aortoesophageal fistula (AEF) is a relatively rare condition that is often life-threatening. Secondary AEF is a complication of previous surgery, which can be more critical and challenging than primary AEF. The number of secondary AEF is increasing due to increase in the number of thoracic endovascular aortic repair (TEVAR). Although TEVAR has become a successful alternative surgical strategy for thoracic aortic aneurysms, secondary AEF after TEVAR might be critical than other secondary AEF because of severe adhesion between the esophagus and residual thoracic aortic wall. This study analyzed six patients with secondary AEF who were treated at Tokyo Medical University Hospital between 2011 and 2016. These participants included four patients who had undergone TEVAR and two who had undergone total arch replacement. Although they were subsequently hospitalized for a long period, open surgical repair was completed in two patients who had undergone total arch replacement. TEVAR alone was performed in two patients who had undergone TEVAR and they were discharged without major complications shortly. Combined repair of TEVAR as a bridge to open surgery was planned for two patients who had undergone TEVAR. However, reconstruction of the aorta and esophagus could not be completed in these patients due to severe adhesions, and they died during hospitalization. Definitive open repair was successfully performed in patients with secondary AEF after total arch replacement. However, in the patients with secondary AEF after TEVAR, severe adhesion between the aorta and esophagus led to difficulty in performing a successful definitive open repair. The strategy for secondary AEF should, therefore, be decided considering the etiology of secondary AEF. In secondary AEF after TEVAR, definitive open repair is difficult to complete because of catastrophic complication, and palliative treatment using TEVAR without reconstruction of aorta and esophagus can be an alternative.


The power of collaboration: integrating a preventive medicine-public health curriculum into a pediatric residency.
This is one of six short papers that describe additional innovations to help integrate public health into medical education; these were featured in the "Patients and Populations: Public Health in Medical Education" conference. They represent relatively new endeavors or curricular components that had not been explored in prior publications. Although evaluation data are lacking, it was considered to be of value to medical educators to share a brief description of the collaboration between the Division of Preventive, Occupational, and Aerospace Medicine and the Department of Pediatrics at Mayo Clinic to integrate a preventive medicine-public health curriculum into the pediatric residency.


Plasma oxalate levels in prevalent hemodialysis patients and potential implications for ascorbic acid supplementation.
Ascorbic acid (AA) supplementation may increase hemoglobin levels and decrease erythropoiesis-stimulating agent dose requirement in patients with end stage renal disease (ESRD). While plasma AA levels >100μM may be supratherapeutic, levels of at least 30μM may be needed to improve wound healing and levels may need to reach 70μM to optimize erythropoiesis. Of concern, oxalate (Ox), an AA metabolite, can accumulate in ESRD. Historically, if plasma Ox levels remain ≥30μM, oxalosis was of concern. Contemporary hemodialysis (HD) efficiencies may decrease the risk of oxalosis by maintaining pre-HD Ox levels <30μM. This study focuses on the plasma Ox levels in HD patients. A prospective, observational study of 197 HD patients with pre-HD AA levels and pre-HD and post-HD Ox levels. Mean plasma Ox levels decreased 71% during the intradialytic period (22.3±11.1μM to 6.4±3.2μM, P<0.001). In regression analysis, pre-HD plasma AA levels ≤100μM were not associated with a pre-HD plasma Ox level≥30μM, even if ferritin levels were increased. Pre-HD plasma Ox levels ≥20 or ≥30μM were not associated with lower cumulative 4-year survival. Pre-HD plasma AA levels up to 100μM in HD patients do not appear to be associated with an increased risk of developing secondary oxalosis, as the corresponding pre-HD plasma Ox level appears to be maintained at tolerable levels.


The state of hormonal contraception today: established and emerging noncontraceptive health benefits.
In the 50 years since the advent of combined oral contraceptives the amount of estrogen in oral contraceptives dropped from over 100 mcg to less than 30 mcg. Many noncontraceptive health benefits have emerged that decrease mortality and improve quality of life. Some of the immediate benefits include improvement of menorrhagia and dysmenorrhea, reduction in premenstrual dysphoric disorder symptoms, and decreased acne. As an effective birth control method oral contraceptives also decrease pregnancy-related deaths by preventing pregnancy. After the reproductive years, previous use of oral contraceptives continues to be beneficial, reducing the risk of death from ovarian and endometrial cancer. All these benefits have held up over time whereas cardiovascular risks have lessened because of the decrease in oral contraceptive pill dosage. Decreased ovarian cyst formation is an example of benefit with higher-dose oral contraceptive formulations that no longer holds true with low-dose pills.


The Dutch 'Focus on Strength' intervention study protocol: programme design and production, implementation and evaluation plan.
Overweight youngsters are better in absolute strength exercises than their normal-weight counterparts; a physiological phenomenon with promising psychological impact. In this paper we describe the study protocol of the Dutch, school-based program 'Focus on Strength' that aims to improve body composition of 11-13 year old students, and with that to ultimately improve their quality of life. The development of this intervention is based on the Intervention Mapping (IM) protocol, which starts from a needs assessment, uses theory and empirical research to develop a detailed intervention plan, and anticipates program implementation and evaluation. This novel intervention targets first year students in preparatory secondary vocational education (11-13 years of age). Teachers are the program implementers. One part of the intervention involves a 30 % increase of strength exercises in the physical education lessons. The other part is based on Motivational Interviewing, promoting autonomous motivation of students to become more physically active outside school. Performance and change objectives are described for both teachers and students. The effectiveness of the intervention will be tested in a Randomized Controlled Trial in 9 Dutch high schools. Intervention Mapping is a useful framework for program planning a school-based program to improve body composition and motivation to exercise in 11-13 year old adolescents by a "Focus on Strength". NTR5676 , registered 8 February 2016 (retrospectively registered).


First metatarsophalangeal joint arthrodiastasis and biologic resurfacing with external fixation: a case report.
The primary goal in the treatment of arthritic joints is elimination of pain associated with limited motion. Several surgical techniques have been developed to treat varying degrees of hallux rigidus of any cause. This case report details an alternative surgical approach to address hallux rigidus and associated hallux valgus deformity through a combination of joint debridement, resurfacing, and arthrodiastasis.


Neuroendoscopy: general aspects and principles.
When used in medicine, endoscopy describes a procedure used to see inside various parts of the body, such as the interior surfaces of an organ, by inserting a tube through a natural or created orifice. The instrument may have a rigid (borescope) or flexible (fiberscope) tube; it provides an image for visual inspection, photography and video-endoscopy and enables acquisition of biopsy specimens, removal of lesions, and retrieval of foreign objects. It is imperative that young neurosurgeons and residents become familiar and comfortable with endoscopic techniques, and it is hoped that they can contribute to the evolution and development of these surgical methods.


Genomic architecture of fetal central nervous system anomalies using whole-genome sequencing.
Structural anomalies of the central nervous system (CNS) are one of the most common fetal anomalies found during prenatal imaging. However, the genomic architecture of prenatal imaging phenotypes has not yet been systematically studied in a large cohort. Patients diagnosed with fetal CNS anomalies were identified from medical records and images. Fetal samples were subjected to low-pass and deep whole-genome sequencing (WGS) for aneuploid, copy number variation (CNV), single-nucleotide variant (SNV, including insertions/deletions (indels)), and small CNV identification. The clinical significance of variants was interpreted based on a candidate gene list constructed from ultrasound phenotypes. In total, 162 fetuses with 11 common CNS anomalies were enrolled in this study. Primary diagnosis was achieved in 62 cases, with an overall diagnostic rate of 38.3%. Causative variants included 18 aneuploids, 17 CNVs, three small CNVs, and 24 SNVs. Among the 24 SNVs, 15 were novel mutations not reported previously. Furthermore, 29 key genes of diagnostic variants and critical genes of pathogenic CNVs were identified, including five recurrent genes: i.e., TUBA1A, KAT6B, CC2D2A, PDHA1, and NF1. Diagnostic variants were present in 34 (70.8%) out of 48 fetuses with both CNS and non-CNS malformations, and in 28 (24.6%) out of 114 fetuses with CNS anomalies only. Hypoplasia of the cerebellum (including the cerebellar vermis) and holoprosencephaly had the highest primary diagnosis yields (>70%), while only four (11.8%) out of 34 neural tube defects achieved genetic diagnosis. Compared with the control group, rare singleton loss-of-function variants (SLoFVs) were significantly accumulated in the patient cohort.


Volumetric 23Na Single and Triple-Quantum Imaging at 7T: 3D-CRISTINA.
To measure multi-quantum coherence (MQC) 23Na signals for noninvasive cell physiological information in the whole-brain, the 2D-CRISTINA method was extended to 3D. This experimental study investigated the use and results of a new sequence, 3D-CRISTINA, on a phantom and healthy volunteers. The 3D Cartesian single and triple-quantum imaging of 23Na (3D-CRISTINA) was developed and implemented at 7T, favoring a non-selective volume excitation for increased signal-to-noise ratio (SNR) and lower energy deployment than its 2D counterpart. Two independent phase cycles were used in analogy to the 2D method. A comparison of 6-steps cycles and 12-steps cycles was performed. We used a phantom composed of different sodium and agarose concentrations, 50mM to 150mM Na+, and 0-5% agarose for sequence validation. Four healthy volunteers were scanned at 7T for whole brain MQC imaging. The sequence 3D-CRISTINA was developed and tested at 7T. At 7T, the 3D-CRISTINA acquisition allowed to reduce the TR to 230ms from the previous 390ms for 2D, resulting in a total acquisition time of 53min for a 3D volume of 4×4×8mm resolution. The phase cycle evaluation showed that the 7T acquisition time could be reduced by 4-fold with moderate single and triple-quantum signals SNR loss. The healthy volunteers demonstrated clinical feasibility at 7T and showed a difference in the MQC signals ratio of White Matter (WM) and Grey Matter (GM). Volumetric CRISTINA multi-quantum imaging allowed whole-brain coverage. The non-selective excitation enabled a faster scan due to a decrease in energy deposition which enabled a lower repetition time. Thus, it should be the preferred choice for future in vivo multi-quantum applications compared to the 2D method. A more extensive study is warranted to explore WM and GM MQC differences.


Clinicopathological correlation and prognostic significance of VEGF-A, VEGF-C, VEGFR-2 and VEGFR-3 expression in colorectal cancer.
Colorectal cancer (CRC) is the third most common type of cancer and the fourth most frequent cause of cancer death. Literature indicates that vascular endothelial growth factor is a predominant angiogenic factor and that angiogenesis plays an important role in the progression of CRC. The present series consisted of tissue samples obtained from 672 patients who had undergone large bowel resection between 2005 and 2010 at the Braga Hospital, Portugal. Archival paraffin-embedded CRC tissue and normal adjacent samples were used to build up tissue microarray blocks and VEGF-A, VEGF-C, VEGFR-2 and VEGFR-3 expression was immunohistochemically assessed. We observed an overexpression of VEGF-C in CRC when tumour cells and normal-adjacent tissue were compared (p=0.004). In tumour samples, VEGF-C-positive cases were associated with VEGFR-3 expression (p=0.047). When assessing the correlation between VEGF-A, VEGF-C, VEGFR-2 and VEGFR-3 expressions and the clinicopathological data, it was revealed that VEGF-A positive cases were associated with male gender (p=0.016) and well-differentiated tumours (p=0.001); VEGF-C with colon cancers (p=0.037), exophytic (p=0.048), moderately-differentiated (p=0.007) and T3/T4 (p=0.010) tumours; VEGFR-2 with invasive adenocarcinoma (p=0.007) and VEGFR-3 with the presence of hepatic metastasis (p=0.032). Overall survival curves for CRC were statistically significant for rectal cancer, VEGF-C expression and stage III (p=0.019) and VEGFR-3 expression and stage IV (p=0.047). Quantification of VEGF-A, VEGF-C, VEGFR-2 and VEGFR-3 expression seems to provide valuable prognostic information in CRC and the correlation with clinicopathological data revealed an association with characteristics that contribute to progression, invasion and metastasis leading to poorer survival rates and prognosis.


The Manifestation of a Patient With Myelofibrosis in 68Ga-DOTA-FAPI-04 PET/CT Mimicking "Super Bone Imaging".
Primary myelofibrosis is a chronic inflammatory disease of the bone marrow. It progresses from an early robust inflammatory state to a more advanced fibrotic response, representing the advanced stage of the disease. We report a 50-year-old woman who was diagnosed with primary myelofibrosis. 18F-FDG PET/CT showed mild uptake in diffuse sclerotic lesions in the bone matrix, whereas 68Ga-DOTA-FAPI-04 showed intense uptake at the whole skeleton.


Soft microfiber-based hollow microneedle array for stretchable microfluidic biosensing patch with negative pressure-driven sampling.
Wearable point-of-care testing devices are essential for personalized and decentralized healthcare. They can collect biofluid samples from the human body and use an analyzer to detect biomolecules. However, creating an integrated system is challenging due to the difficulty of achieving conformality to the human body, regulating the collection and transport of biofluids, developing a biosensor patch capable of precise biomolecule detection, and establishing a simple operation protocol that requires minimal wearer attention. In this study, we propose using a hollow microneedle (HMN) based on soft hollow microfibers and a microneedle-integrated microfluidic biosensor patch (MIMBP) capable of integrated blood sampling and electrochemical biosensing of biomolecules. The soft MIMBP includes a stretchable microfluidic device, a flexible electrochemical biosensor, and a HMN array made from flexible hollow microfibers. The HMNs are fabricated by electroplating flexible and mechanically durable hollow microfibers made from a nanocomposite matrix of polyimide, a poly (vinylidene fluoride-co-trifluoroethylene) copolymer, and single-walled carbon nanotubes. The MIMBP uses the negative pressure generated by a single button push to collect blood and deliver it to a flexible electrochemical biosensor modified with a gold nanostructure and Pt nanoparticles. We have demonstrated that glucose can be accurately measured up to the molar range in whole human blood collected through the microneedle. The MIMBP platform with HMNs has great potential as a foundation for the future development of simple, wearable, self-testing systems for minimally invasive biomolecule detection. This platform capable of sequential blood collection and high sensitivity glucose detection, which are ideal for personalized and decentralized healthcare.


Recombining germline-derived CDR sequences for creating diverse single-framework antibody libraries.
We constructed a single-chain Fv antibody library that permits human complementarity-determining region (CDR) gene fragments of any germline to be incorporated combinatorially into the appropriate positions of the variable-region frameworks VH-DP47 and VL-DPL3. A library of 2 x 109 independent transformants was screened against haptens, peptides, carbohydrates, and proteins, and the selected antibody fragments exhibited dissociation constants in the subnanomolar range. The antibody genes in this library were built on a single master framework into which diverse CDRs were allowed to recombine. These CDRs were sampled from in vivo-processed gene sequences, thus potentially optimizing the levels of correctly folded and functional molecules, and resulting in a molecule exhibiting a lower computed immunogenicity compared to naive immunoglobulins. Using the modularized assembly process to incorporate foreign sequences into an immunoglobulin scaffold, it is possible to vary as many as six CDRs at the same time, creating genetic and functional variation in antibody molecules.


Serologic Surveillance for SARS-CoV-2 Infection among Wild Rodents, Europe.
We report results from serologic surveillance for exposure to SARS-CoV-2 among 1,237 wild rodents and small mammals across Europe. All samples were negative, with the possible exception of 1. Despite suspected potential for human-to-rodent spillover, no evidence of widespread SARS-CoV-2 circulation in rodent populations has been reported to date.Esitämme tulokset serologisesta tutkimuksesta, jossa seulottiin SARS-CoV-2 tartuntojen varalta 1,237 luonnonvaraista jyrsijää ja piennisäkästä eri puolilta Eurooppaa. Kaikki näytteet olivat negatiivisia, yhtä näytettä lukuun ottamatta. SARS-CoV-2:n läikkymisen ihmisistä jyrsijöihin on arveltu olevan mahdollista, mutta todisteet viruksen laajamittaisesta leviämisestä jyrsijäpopulaatioissa puuttuvat.


Resting energy expenditure in children following major operative procedures.
Resting energy expenditure (REE) is reported to increase by 24% in adults following elective operations; however, similar data are not available for children. We studied REE in 12 children (14 operative procedures) to test the hypothesis that children experience a similar rise in REE as adults following operation. The operations included endorectal pull-through, gastric resection, ileostomy closure, and other major abdominal procedures. REE was measured daily by indirect calorimetry using a computerized bedside metabolic cart. All subjects (7 males, 5 females; age range, 8 to 19 years; mean age, 14.7 years) were measured supine, in bed, and after an overnight fast. REE was expressed as kilocalories per unit body surface area (BSA) per day. In addition, respiratory quotient (RQ) was calculated for each patient. Contrary to adults, these children did not demonstrate a significant increase in REE following major operative procedures. Furthermore, there was no change in RQ postoperatively. These data demonstrate that children might have a different response to surgical stress than adults. We theorize that children are able to convert energy expended on growth to energy spent on wound repair and healing, thus avoiding the overall increase in energy expenditure seen in the adult population.


Natural selection on the plant-water relations of Cleome serrulata growing along natural moisture gradients.
I investigated the extent and adaptive importance of genetically-based variation in plant water relations in two populations of the annual plant Cleome serrulata found growing along relatively short (<30 m) and mild soil moisture gradients. Field measurements of predawn plant water potentials showed that plants at the dry end of the moisture gradients had consistently lower ψPlant in May and June of 1984; differences up to 0.9 MPa were seen along the gradients. Seeds were collected from maternal plants growing along the moisture gradients and then grown under well-watered conditions in the greenhouse. Pressure-volume curves were constructed for a total of 92 seedlings from 25 maternal plants when the seedlings were four weeks old.Considerable genetic variation in the four highly correlated water potential components was seen in both populations, suggesting relatively high heritabilities (h2≈0.5). A partial correlation analysis revealed that cell wall elasticity was higher in seedlings from maternal plants which grew in the dry portions of each site. This suggested that natural selection had acted on this character during one or more previous generations. It appears that slight variations in the physiological genotype can significantly affect overall fitness in C. serulata.


Removal of recalcitrant organic matter of landfill leachate by adsorption onto biochar from sewage sludge: A quali-quantitative analysis.
Sewage sludge is a byproduct of sewage treatment, whereas landfill leachate is a complex wastewater generated by the decomposition of solid waste. These byproducts require adequate management, and one option for the sludge is the thermal treatment by pyrolysis to produce biochar. The resulting biosolid can be used as an adsorbent to treat landfill leachate. The main objective of this research was to remove recalcitrant organic matter from landfill leachate by adsorption onto biochar produced from sewage sludge. Aerobic and anaerobic sludges were pyrolyzed at 450, 650 and 850 °C, under residence times of 60, 90 and 120 min. Temperature had a positive and more significant impact on the characteristics of the biochars produced, and consequently on the adsorption of recalcitrant organic matter. However, the impact of residence time was less intense and, in some cases negative. Biochars produced from both aerobic and anaerobic sludge pyrolyzed at 850 °C for 120 and 60 min, respectively, showed higher specific surface areas (114.4 m2g-1 and 104.2 m2g-1, respectively) compared with those pyrolyzed at 450 °C and 650 °C. The biochar from anaerobic sludge produced at 850 °C and 60 min showed the best performance regarding the adsorption process, with chemical oxygen demand (COD), dissolved organic carbon (DOC), and color removals from the leachate of 32%, 36%, and 41%, respectively. The results of adsorption capacity for this biochar from anaerobic sludge were 26.1 mg g-1 for COD and 7.9 mg g-1 for DOC. The adsorption of recalcitrant organic matter from leachate was evidenced by the decrease in the UV-Vis absorbances and fluorescence intensities. It indicates that recalcitrant and humic substances were removed mainly by biochars pyrolyzed at 850 °C. Thus, the results allow to stress that the pyrolysis of sewage sludge to produce biochar is a promising alternative to sludge treatment, and the biochar may be applied as a pre-treatment of landfill leachate since it successfully removed the recalcitrant organic matter.


The "non-preventable" preventable transfer? An analysis of the care from support services that injured children transferred to a level 1 pediatric trauma center receive.
Almost 30% of pediatric trauma transfers to our facility have previously been shown to be potentially preventable transfers (PT). However, we sought to evaluate what care from support services these PT received during admission. Traumatically injured children transferred between January 2014 and June 2019 were retrospectively analyzed. A PT was defined as a child who was discharged within 36 h of arrival without surgical intervention or advanced imaging studies. PT that received support services were compared to those that did not to determine which patients may benefit from these services were their transfers prevented. There were 3212 transfers, and 927 (29%) were PT. When compared to non-PT, PT were younger, closer to our hospital, and had a lower ISS, extremity or C-spine injury, or assault/non-accidental trauma mechanism. PT were less likely to have a chest injury or a CT at the referring hospital. Of the PT, 30% had a support service consulted. PT with higher ISS or a head injury was more likely to receive a consultation with a support service. A significant proportion of these "preventable" transfers still receive important care from support services during their admission. Retrospective study. III.


Kallikrein-related peptidase 8-dependent skin wound healing is associated with upregulation of kallikrein-related peptidase 6 and PAR2.
Kallikrein-related peptidase 8 (KLK8) is believed to be involved in the maintenance of skin homeostasis and pathogenesis of inflammatory skin diseases. Although previous studies have shown that KLK8 is expressed around incisional wounds, the exact role of KLK8 in wound healing remains obscure. In the present study, we compared wound healing in wild-type (WT) and Klk8 gene-disrupted (kallikrein-related peptidase 8 knockout, Klk8(-/-)) mouse skin. Wound healing in Klk8(-/-) mice was hampered with defective keratinocyte proliferation, differentiation, and migration in the early stages of wound healing. Compared with the prominent induction of Klk6 and protease-activated receptor 2 (PAR2) messenger RNA, and protein in WT mice after wounding, a much lower increase was observed in Klk8(-/-) skin. After skin wounding in WT mice, increased Klk6 was detected from the upper stratum spinosum to the stratum corneum. Moreover, in WT mice, Klk6 protein was processed. PAR2 was diffusely expressed in the cytoplasm of the stratum spinosum at day 7 post wounding in WT mice. These results suggest that Klk8 is involved in the proliferation and migration of keratinocytes through the upregulation and activation of Klk6 in the early stages of wound healing, and possibly in keratinocyte differentiation associated with the upregulation and activation of PAR2 in the late stages of wound healing.


Fast and Accurate Data Extraction for Near Real-Time Registration of 3-D Ultrasound and Computed Tomography in Orthopedic Surgery.
Automatic, accurate and real-time registration is an important step in providing effective guidance and successful anatomic restoration in ultrasound (US)-based computer assisted orthopedic surgery. We propose a method in which local phase-based bone surfaces, extracted from intra-operative US data, are registered to pre-operatively segmented computed tomography data. Extracted bone surfaces are downsampled and reinforced with high curvature features. A novel hierarchical simplification algorithm is used to further optimize the point clouds. The final point clouds are represented as Gaussian mixture models and iteratively matched by minimizing the dissimilarity between them using an L2 metric. For 44 clinical data sets from 25 pelvic fracture patients and 49 phantom data sets, we report mean surface registration accuracies of 0.31 and 0.77 mm, respectively, with an average registration time of 1.41 s. Our results suggest the viability and potential of the chosen method for real-time intra-operative registration in orthopedic surgery.


Impact of acute rejection and new-onset diabetes on long-term transplant graft and patient survival.
Development of new therapeutic strategies to improve long-term transplant outcomes requires improved understanding of the mechanisms by which these complications limit long-term transplant survival. The association of acute rejection and new-onset diabetes was determined in the first posttransplantation year with the outcomes of transplant failure from any cause, death-censored graft loss, and death with a functioning graft in 27,707 adult recipients of first kidney-only transplants, with graft survival of at least 1 yr, performed between 1995 and 2002 in the United States. In multivariate analyses, patients who developed acute rejection or new-onset diabetes had a similar risk for transplant failure from any cause, but the mechanisms of transplant failure were different: Acute rejection was associated with death-censored graft loss but only weakly associated with death with a functioning graft. In contrast new-onset diabetes was not associated with death-censored graft loss but was associated with an increased risk for death with a functioning graft. Acute rejection and new-onset diabetes have a similar impact on long-term transplant survival but lead to transplant failure through different mechanisms. The mechanisms by which new-onset diabetes leads to transplant failure should be prospectively studied. Targeted therapeutic strategies to minimize the impact of various early posttransplantation complications may lead to improved long-term outcomes.


Spirituality and coping with life stress among adult survivors of childhood sexual abuse.
The purpose of this study was to explore the role of spiritual coping in adult survivors' responses to current life stressors. Although there has been research on general coping and adult survivors of childhood sexual abuse (CSA), there has been no work done on spiritual coping behaviour and survivors' current adjustment. One hundred and one adult survivors of childhood sexual abuse volunteered to participate in this study. Survivors were recruited through advertisements placed in various community venues. Survivors completed questionnaires on abuse descriptors, the coping resources of social support and general cognitive appraisal, spiritual coping and current distress. Spiritual coping was assessed in relation to a current negative life event. In general, spiritual coping predicted the current distress of adult survivors beyond the contribution of demographics, severity of abuse, cognitive appraisal and support satisfaction. For example, self-directed (beta=.27), active surrender (beta=.32), and passive deferral (beta=-.35) significantly contributed to the prediction of anxious mood, [F(15, 60)=3.31, p<.0001], while only spiritual discontent (beta=.26) predicted depressive mood, [F(15, 60)=3.66, p<.0001] beyond the contribution of other factors. Negative forms of spiritual coping (e.g., spiritual discontent) tend to be related to greater distress, while more positive forms of spiritual coping (e.g., spiritual support) were related to less distress. For instance, spiritual discontent coping was related to greater depressive mood, while active surrender coping and religious forgiveness coping (i.e., seeking God's help to relinquish negative emotion) were associated with lower levels of depressive mood. The results highlight the importance of making a distinction between negative and positive forms of spiritual coping when investigating the role of spirituality in the current life functioning of adult survivors of childhood sexual abuse.


Analysis of Acquisition of COVID-2019 Neutralizing Antibodies in Organ Transplant Recipients.
This study confirmed the kinetics of antibodies acquired by SARS-CoV-2 vaccination in solid-organ transplant recipients and examined their association with the development of COVID-19 and immunosuppressive status in organ transplant recipients. We measured COVID-19 neutralizing antibody titer in 21 organ transplant recipients vaccinated with the COVID-19 vaccine and 14 nontransplant recipients (control group) 3 times before and at 1 and 6 months after the third dose of vaccine. By confirming the kinetics of the acquired antibodies, we examined the relevance of the background characteristics of organ transplant recipients, such as the development of infectious diseases and immunosuppressive status. The proportion of patients with neutralizing antibodies was significantly higher in the nontransplant group than in the transplant group. Neutralizing antibody titers were significantly lower in transplant recipients when they were compared before the third dose and 1 month later. In the transplant recipient group, 11 patients were positive, and 10 were negative for neutralizing antibodies. When the causal relationship between the neutralizing antibody titer and background was examined, a positive correlation was found between the antibody titer and the number of years since transplantation, and a negative correlation was found between the tacrolimus trough values, amount of mycophenolate mofetil or steroids taken internally, and antibody titer. This study suggests that the effectiveness of vaccination in transplant recipients is associated with the post-transplant period before vaccination and the dose of immunosuppressive agents.


APPLICABILITY OF RHEOLOGICAL MODELS TO THE INTERPRETATION OF FLOW AND PROCESSING BEHAVIOUR OF FLUID FOOD PRODUCTS.
This review is concerned with the non-Newtonian behaviour of selected fluid food products and, in particular, with the applicability of the power law. Some alternative models are included which food scientists might find useful in correlating flow properties. The interpretation of rheological characteristics in terms of structure and consistency is mentioned and the need for more detailed studies, particularly with regard to thermodynamic aspects, is pointed out. Application of the power law model to food processing is illustrated with principles of heat transfer and mixing of non-Newtonian foodstuffs.


New drug prescribing by hospital doctors: the nature and meaning of knowledge.
In the UK the high cost of new drugs is partly accountable for the growth in spending on prescription drugs. Most prescribing takes place in general practice and the influence of secondary care prescribing on primary care prescribing is well recognized; yet the factors that influence hospital prescribing have been little researched. Drawing on accounts of actual prescribing events from hospital doctors from a range of specialties, we investigated the processes by which new drugs come into practice, from hospital doctors' awareness of new drugs to the assimilation and interpretation of evidential sources. The determinants of new drug prescribing were interconnected within four forms of knowledge: scientific knowledge, social knowledge, patient knowledge and experiential knowledge. Furthermore, the nature of knowledge could only be understood within its situated context. The revelation of multiple and contingent forms of knowledge highlights the problematic nature of knowledge construction within the approaches of evidence-based medicine.


c-maf in multiple myeloma: an oncogene enhancing tumor-stroma interactions.
Gene expression profiling studies reported by Hurt et al. in this issue of Cancer Cell reveal an unexpectedly frequent overexpression of c-maf in multiple myeloma and identify molecular targets of c-maf transactivation. The results define c-maf as a prototype of a class of oncogenes that not only stimulate cell cycle progression, but also promote pathological interactions between tumor and stroma cells.


Supportive strategies for nonverbal communication with persons living with dementia: A scoping review.
Many people living with dementia experience challenges comprehending language and benefit from nonverbal communication supports. Little published empirical evidence exists for care partners regarding supportive strategies for nonverbal communication with people living with dementia. This study aimed to conduct a scoping review of nonverbal strategies for care partners which have been observed to support communication with people living with dementia. Current best practices for scoping research guided this review. CINAHL, PsycInfo, Scopus, and Pubmed databases were searched December 8, 2020. Empirical studies that examined the supportiveness of nonverbal communication strategies used by care partners of people living with dementia were eligible. All publication dates were included. Eligible studies were published in English in peer-reviewed journals. Studies were screened first by title and abstract, and subsequently by full-text review. Data charting was conducted using an evidence summary table, which was subsequently used for analysis. Results were presented in the form of a written summary. Sixteen studies were included in the final review. Six categories of supportive nonverbal communication strategies were identified: eye contact, gestures, facial expression, touch, close proximity, and frontal orientation. Studies observed six outcomes which indicated that these nonverbal strategies were supportive for communication with people living with dementia; however, person-centered outcomes were limited. The review identified supportive nonverbal communication strategies used by care partners with people living with dementia in the current literature. Disagreement exists in the literature regarding which outcomes define supportive nonverbal communication with people living with dementia. This in combination with the benefits of person-centered approaches to care with people living with dementia presents a critical need to delineate which nonverbal communication strategies are person-centered in future research. Six supportive nonverbal communication strategies identified by scoping literature review, but there is disagreement in how the literature defines "supportive" @marie_y_s @EmmaBender19.


A novel method for converting apolipoprotein B, the major protein moiety of human plasma low density lipoproteins, into a water-soluble protein.
We have developed a new technique to solubilize apolipoprotein B (ApoB) in aqueous solutions. The procedure involves stirring ApoB in 6 M guanidine/20 mM NH4Cl/NH4OH in the presence of cupric ammonia complexes at pH 9.7 for 20 h in N2, and then removing these reagents by a series of dialysis in N2. The resulting Cu(NH3)4(2)+-treated (Cu2+-treated) ApoB is soluble in aqueous buffers of pH above 8.3 or below 3. Parallel experiments carried out on control proteins, human albumin, alpha-lactalbumin, and insulin, indicated no change in molecular weight and no creation of a new NH2-terminal amino acid after Cu2+-treatment. By Edman degradation, the Cu2+-treated ApoB showed no detectable NH2-terminal amino acid. These results showed that the mechanism of Cu2+-solubilization of ApoB was not due to the cleavage of peptide bonds. Electrophoresis on urea-polyacrylamide gel, Cu2+-treated ApoB showed the same number of bands as the non-treated ApoB in the separating gels (7%) near the cathode, suggesting the heterogeneity of ApoB. In SDS-polyacrylamide gel (10%), the reduced and Cu2+-treated ApoB migrated with the similar mobilities to the monomer or dimer of human albumin. Antibodies raised against Cu2+-treated ApoB gave at least two immunoprecipitin lines against the Cu2+-treated ApoB as well as the non-treated guanidine-HCl-soluble ApoB, suggesting the presence of non-identical subunits.


Information transmission in multi-input-output stochastic neuron models.
The Shannon's information theory in multi-way channels (Shannon, 1961) is applied to multi-input-output relations of the stochastic automaton models for interaction of excitatory and inhibitory impulse sequences proposed in the previous papers (Tsukada et al., 1977). In these models, the output spike train depends upon several statistical characteristics (mean frequency, standard deviation, form, order-dependence or order-independence, etc.) of the excitatory and inhibitory input spike trains. By the use of the multiple-access channel in information theory, some stochastic properties of temporal pattern discrimination in neurons are analyzed and discussed with biological systems.


Prenatal diagnosis and psychological distress: amniocentesis or chorionic villus biopsy?
The psychological reactions of 211 women undergoing prenatal diagnosis (PND) with amniocentesis (group A, n = 122) or chorionic villus biopsy (group V, n = 90) were examined by questionnaires and interviews. The distress experienced while waiting for the test, during the test procedure, and while waiting for the result was reported by the women, both in questionnaires and in interviews. In the questionnaires, no difference between the two diagnostic methods was observed. In the interviews, however, the women undergoing amniocentesis appeared significantly more distressed by the procedure. In group A 97 per cent and in group V 100 per cent wished a method which, like chorionic villus biopsy, could be used in the first weeks of pregnancy. The risk of miscarriage was, as described in other studies, regarded as a serious threat by the pregnant women.


Assembly of the active form of the transposase-Mu DNA complex: a critical control point in Mu transposition.
Discovery and characterization of a new intermediate in Mu DNA transposition allowed assembly of the transposition machinery to be separated from the chemical steps of recombination. This stable intermediate, which accumulates in the presence of Ca2+, consists of the two ends of the Mu DNA synapsed by a tetramer of the Mu transposase. Within this stable synaptic complex (SSC), the recombination sites are engaged but not yet cleaved. Thus, the SSC is structurally related to both the cleaved donor and strand transfer complexes, but precedes them on the transposition pathway. Once the active protein-DNA complex is constructed, it is conserved throughout transposition. The participation of internal sequence elements and accessory factors exclusively during SSC assembly allows recombination to be controlled prior to the irreversible chemical steps.


Pharmacological assessment of m1 muscarinic acetylcholine receptor-gq/11 protein coupling in membranes prepared from postmortem human brain tissue.
Using a selective Galpha(q/11) protein antibody capture guanosine 5'-O-(3-[35S]thio)triphosphate ([35S]GTPgammaS) binding approach, it has been possible to perform a quantitative pharmacological examination of the functional activity of the M(1) muscarinic acetylcholine receptor (mAChR) in membranes prepared from human postmortem cerebral cortex. Oxotremorine-M caused a > or = 2-fold increase in [35S]GTPgammaS-Galpha(q/11) binding with a pEC(50) of 6.06 +/- 0.16 in Brodmann's areas 23 and 25 that was almost completely inhibited by preincubation of membranes with the M(1) mAChR subtype-selective antagonist muscarinic toxin-7. In addition, the orthosteric and allosteric agonists, xanomeline [3(3-hexyloxy-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine] and AC-42 (4-n-butyl-1-[4-(2-methylphenyl)-4-oxo-1-butyl]-piperidine hydrogen chloride), increased [35S]-GTPgammaS-Galpha(q/11) binding, but with reduced intrinsic activities, inducing maximal responses that were 42 +/- 1 and 44 +/- 2% of the oxotremorine-M-induced response, respectively. These data indicate that the M(1) receptor is the predominant mAChR subtype coupling to the Galpha(q/11) G protein in these brain regions and that it is possible to quantify the potency and intrinsic activity of full and partial M(1) mAChR receptor agonists in postmortem human brain using a selective Galpha(q/11) protein antibody capture [35S]GTPgammaS binding assay.


Effect of aminoglycosides on proximal tubular membranes of the human kidney.
The effect of the aminoglycosides amikacin, gentamicin, netilmicin sisomicin and tobramycin on the proximal tubule of the human kidney was investigated in 78 healthy subjects. Fifteen adults were each given gentamicin, sisomicin or tobramycin 3 mg/kg bodyweight, 10 subjects received netilmicin 3 mg/kg or amikacin 15 mg/kg additionally seven subjects amikacin 10 mg and six subjects netilmicin 6 mg on three consecutive days. The principal enzyme of the brush border membrane of the proximal tubule, alanine aminopeptidase (AAP), was determined enzymatically and immunologically in 24-hour urines. The effects of the various aminoglycosides on the membranes were different. Less of membrane AAP was greatest after amikacin and was least after tobramycin. There was no difference between gentamicin, netilmicin, and sisomicin, which had an effect intermediate between the other two compounds. The elimination of AAP occurred at intervals which might possibly have been caused by impairment of cell cycles.


Self-reported efficacy and safety of infliximab and adalimumab biosimilars after non-medical switch in patients with inflammatory bowel disease: results of a multicenter survey.
Few data are available on subjective disease control and perception of adverse events (AEs) during switching from original anti-TNF agents to biosimilars. Hungarian patients with inflammatory bowel disease were interviewed after a mandatory non-medical switch from an infliximab (IFX) originator to a biosimilar GP1111 or from an adalimumab (ADA) originator to a biosimilar GP2017. Drug choice was based on patient's and physician's decision. Subjective efficacy was measured using a 10-point scale, and AEs were assessed. Difference in efficacy before and after the switch was compared within and between the drugs. Seventy-three ADA and 106 IFX switching patients were interviewed. Subjective efficacy of IFX biosimilar was rated lower compared to IFX originator (8.72 ± 1.68 vs. 7.77 ± 2.34; p = 0.001). The ADA biosimilar was rated higher than its originator (9.02 ± 1.61 vs. 8.42 ± 1.93; p = 0.017). Patients receiving ADA biosimilar were more satisfied with the new treatment compared to IFX (p = 0.032). The incidence of new AEs was 85% in the ADA and 55% in the IFX group (1.79 vs. 0.93 AEs per patient, respectively, p < 0.001). Subjective efficacy of switching to a biosimilar was proven in case of ADA, while reduced efficacy was experienced with IFX biosimilar. Perception of AEs was high and varied between biosimilars.


Risk of Immediate-Type Allergy to Local Anesthetics Is Overestimated-Results from 5 Years of Provocation Testing in a Danish Allergy Clinic.
Local anesthetics (LAs) are used in many health care settings and exposure during a lifetime is almost inevitable. Immediate-type allergy to LAs is considered rare among allergy experts but is commonly suspected by health care workers from other specialties, and by patients. The main aim of this study was to investigate the incidence of immediate-type allergy to LAs in our regional allergy clinic over the 5-year period 2010 to 2014. This was a retrospective single-center study of patients referred to a regional allergy clinic (excluding patients with perioperative reactions) with suspected immediate allergy to LAs, who had undergone subcutaneous provocation with 1 or more LAs. Patients were identified in the hospital clinical coding system and clinical information about the reaction and investigation results was obtained from their medical records. A total of 164 patients (123 women/41 men; median age, 56 years; range, 7-89 years) who had 189 provocations with LAs were included over the 5-year period 2010 to 2014. All 164 patients had negative subcutaneous provocations to all 189 tests with LAs (95% CI, 0%-1.83%). Another allergen was identified in 10% (n = 17) of the patients. None of the 164 patients with suspected immediate-type allergy to LAs reacted on provocation. Thus, no patients have been diagnosed with an immediate allergy to LAs in our regional allergy clinic in the 5-year period studied, and allergy to LAs must be considered very rare. Alternative mechanisms should be considered, but if symptoms are consistent with allergy, other potential allergens should be investigated.


Excretion of methylated nucleic acid bases as an indicator of exposure to nitrosatable drugs.
Urinary excretion of 3-methyladenine (3-meA) may be a valuable monitor of exposure to methylating carcinogens. In rats, the compound is known to be liberated from DNA following its formation, is not metabolized and is excreted intact in the urine. Studies with rats administered d3-methylating agents [e.g., a mixture of d6-aminopyrine (d6-AP) and nitrite which liberates d3-N-nitrosodimethylamine (NDMA) intragastrically] have confirmed that d3-3-meA is excreted in a dose-related manner. Although low levels of 'background' 3-meA have been found in rat and human urine, these are about 1000-fold lower than those of 7-methylguanine (7-meG). Thus, despite the fact that 3-meA is known to be formed at 10% of the level of 7-MeG in DNA following exposure of rats to methylating agents, the low 'background' that we have observed indicates that urinary 3-meA should be a more sensitive indicator of methylation than 7-meG.


The binding of sterol sulfates to hamster spermatozoa.
Spermatozoa obtained from the cauda epididymidis possess twice the ability to take up sterol sulfates in vitro when compared to sermatozoa obtained from the caput. This would suggest that a modification of the membrane composition of the spermatozoa occurs during passage through the epididymis. Free sterols are taken up in a similar pattern. Radioautographic studies reveal that, for sterol sulfates, this uptake occurs selectively in the regions of the head and mid-piece of the spermatozoa whereas the free sterols are distributed evenly throughout the length of the spermatozoa. The binding of sterol sulfates to spermatozoa appears to involve sites that are unsaturable. The possibility exists that sterol sulfates, previously implicated in membrane stabilization, may play a similar role in spermatozoa.


A life-threatening infection: Fournier's gangrene.
Fournier's gangrene is a life-threatening disorder in which infection of the perineum and scrotum spreads along fascial planes, causing soft tissue necrosis. If urgent surgery is delayed, the disease will soon result in septic shock, multiorgan failure, and death. In this study, we present 21 patients with Fournier's gangrene who were treated in period between 1994 and 2001. Patients' charts were reviewed retrospectively and are discussed in the light of literature. All patients received aggressive surgical debridment. Penicillin or Ceftriaxone, aminoglicoside and metronidazole were administered intravenously. Of the 21 patients, 5 had scrotal carbuncle, 1 had urethral stricture, 1 had chronic indwelling urethral catheterization, 2 had perirectal abscess, and 1 had hemorrhoidectomy. In eleven patients we couldn't identify any cause. Twelve patients had diabetes mellitus, and two had chronic alcoholism. Escherichia coli was isolated in 12 purulent tissue cultures, and Bacteroides fragilis in eight. Seventeen patients survived, whereas four died. Fourier's gangrene is considered a surgical emergency. Early surgical intervention is essential, as the gangrene can spread rapidly at rates reaching 2 mm per hour. So that Fournier's gangrene is an abrupt, rapidly progressive, gangrenous infection of the external genitalia and perineum and is a real urologic emergency.


Evolutionary aspects of variant types of rat mitochondrial DNA'S.
Mitochondrial DNA's (mtDNAs) were prepared from various kinds of individual Norway rats, Rattus norvegicus, and from three types of individual black rats, Rattus rattus, (Asian type, Ceylon type, and Oceanian type). Intra- and interspecies divergence of their mtDNA sequences were calculated based on changes in restriction endonuclease cleavage sites. The extent of intraspecies divergence of black rats (about 8%) is much larger than that of Norway rats (1%) and the mtDNA of Asian-type black rats resembles the mtDNA of Norway rats more closely than it resembles the mtDNA of other types of black rats. These results strongly suggest that during the course of intraspecies differentiation of black rats, probably long after the separation of the three types of black rats, some Asian-type black rats were isolated sexually and formed a new species, Norway rats. On the basis of our observations we propose a hypothetical process to explain the evolution of animal mtDNA.


Characteristics of menstruation-related problems for adolescents and premarital women in Korea.
This study was undertaken to compare the patterns of menstruation-related problems between adolescents and premarital women who visited the Young Lady Clinic (YLC) at Samsung Medical Center. This study includes 646 adolescents (aged 10-20, group I) and 591 premarital young women (aged 21-30, group II) who visited the YLC with menstruation-related problems (amenorrhea, oligomenorrhea, dysmenorrhea, abnormal uterine bleeding (AUB), etc.). Comparisons between the two groups were made with the use of chi(2)-test and Fisher's exact test. For primary amenorrhea, hypogonadotropic hypogonadism was more frequent in group I (p = 0.007), and eugonadism in group II (p = 0.0025). Chromosomal competent ovarian failure (p = 0.003) and hyperprolactinemia (p < 0.001) were more frequent causes of secondary amenorrhea in group II. Endometriosis without ovarian endometrioma was the more frequent laparoscopic finding for patients of group I (p = 0.0429). Regarding AUB, dysfunctional uterine bleeding (DUB) was more frequent for group I (p < 0.001) and endocrinopathies (p = 0.006) and benign lesions of genital tract (p < 0.0001) for group II. The menstruation-related problems showed different features for each group. These data might give us an insight, at least in part, into the menstruation-related problems of Korean young women.


Biocatalyst developed with recovered iron-rich minerals enhances the biotransformation of SARS-CoV-2 antiviral drugs in anaerobic bioreactors.
The biotransformation of the SARS-CoV-2 antiviral drugs, ribavirin and tenofovir, was studied in methanogenic bioreactors. The role of iron-rich minerals, recovered from a metallurgic effluent, on the biotransformation process was also assessed. Enrichment of anaerobic sludge with recovered minerals promoted superior removal efficiency for both antivirals (97.4 % and 94.7 % for ribavirin and tenofovir, respectively) as compared to the control bioreactor lacking minerals, which achieved 58.5 % and 37.9 % removal for the same drugs, respectively. Further analysis conducted by liquid chromatography coupled to mass spectroscopy revealed several metabolites derived from the biotransformation of both antivirals. Interestingly, tracer analysis with 13CH4 revealed that anaerobic methane oxidation coupled to Fe(III) reduction occurred in the enriched bioreactor, which was reflected in a lower content of methane in the biogas produced from this system, as compared to the control bioreactor. This treatment proposal is suitable within the circular economy concept, in which recovered metals from an industrial wastewater are applied in bioreactors to create a biocatalyst for promoting the biotransformation of emerging pollutants. This strategy may be appropriate for the anaerobic treatment of wastewaters originated from hospitals, as well as from the pharmaceutical and chemical sectors.


Deletion of MGF-110-9L gene from African swine fever virus weakens autophagic degradation of TBK1 as a mechanism for enhancing type I interferon production.
African swine fever (ASF) caused by African swine fever virus (ASFV) is a devastating disease for the global pig industry and economic benefit. The limited knowledge on the pathogenesis and infection mechanisms of ASF restricts progress toward vaccine development and ASF control. Previously, we illustrated that deletion of the MGF-110-9L gene from highly virulent ASFV CN/GS/2018 strains (ASFV∆9L) results in attenuated virulence in swine, but the underlying mechanism remains unclear. In this study, we found that the difference in virulence between wild-type ASFV (wt-ASFV) and ASFV∆9L strains was mainly caused by the difference in TANK Binding Kinase 1 (TBK1) reduction. TBK1 reduction was further identified to be mediated by the autophagy pathway and this degradative process requires the up-regulation of a positive autophagy regulation molecule- Phosphatidylinositol-4-Phosphate 3-Kinase Catalytic Subunit Type 2 Beta (PIK3C2B). Moreover, TBK1 over-expression was confirmed to inhibit ASFV replication in vitro. In summary, these results indicate that wt-ASFV counteracts type I interferon (IFN) production by degrading TBK1, while ASFVΔ9L enhanced type I IFN production by weakening TBK1 reduction, clarifying the mechanism that ASFVΔ9L present the attenuated virulence in vitro.


[Atrial fibrillation and anticoagulation: general practitioner, cardiologist and patient's points of view].
This French study was set up to collect perceptions of general practitioners (GPs), cardiologists and patients on anticoagulation therapy with vitamin K antagonists (VKA) in the management of thromboembolic risk in atrial fibrillation (AF). This is a prospective survey conducted in France, between July 1 and August 7 2011, on a sample defined to obtain a sufficient number of patient files of 133 physicians, divided into 65 cardiologists and 68 GPs. Three hundred and ninety-four patients on VKA and 130 patients not receiving VKA were included in this study. For more than one in three patients, AF was diagnosed incidentally in a medical consultation for another reason. In addition, 15% and 23% of diagnoses of FA were performed after hospitalization for stroke or TIA by cardiologists and GPs, respectively. According to the patient, the doctor contacted first is a GP (52% for the GP vs. 35.5% for the cardiologist), but they state that the diagnosis was made mainly by a cardiologist (63% for the cardiologist vs. 27% for the GP). In 78% of cases, cardiologists are initial prescribers. A CHADS2 score of 0 was found in 23% of patients not receiving VKA and in 11% of patients on VKA. A CHADS2 score superior or equal to 2 is significantly more frequently found in patients with paroxysmal AF. Concerning the monitoring of the patient, GPs ensure mainly monitoring of INR. In terms of compliance, according to doctors, their patients systematically take their treatment in 91% of cases. However, by interviewing patients, 60% of non-compliant patients are considered compliant by their physician. This study has achieved an overview of anticoagulation treatment in AF, in France. The initiation is mainly ensured by the cardiologist and the monitoring by the GP. Assessments between cardiologists and GPs are relatively similar, however, it appears that anticoagulation treatment is under-prescribed for the patients at risk.


Genetic diversity and population structure analysis of Paris polyphylla Sm. revealed by SSR marker.
Paris polyphylla Sm. is a vulnerable medicinal plant distributed in the Himalayan countries. This plant has numerous pharmacological benefits, including anticancer, anti-inflammatory, analgesic, and antipyretic properties. The distribution, conservation status, and traditional usage of this species are fairly known in Nepal. However, its diversity and population structure at the molecular level are unexplored. This study analyzes, the genetic diversity and population structure of 32 P. polyphylla germplasms collected from Central, Eastern and Western regions of Nepal using 15 simple sequence repeat (SSR) markers. All the SSR primers were polymorphic and amplified 60 alleles ranging from 50 bp to 900 bp. The polymorphic information content (PIC) value ranged from 0 to 0.75. The average value of the observed heterozygosity (Ho), expected heterozygosity (He), Shannon's information index (I), and total heterozygosity (Ht) were 0.63, 0.53, 0.92 and 0.32, respectively. The analysis of molecular variance (AMOVA), showed a maximum variation of 74% within the individual in a population and only 26% variation among the population. In the population STRUCTURE analysis two clusters were formed where Eastern germplasms (EN) were separated far from the Central and Western germplasms (CWN), this clustering was in complete correspondence to the unweighted pair group method based on arithmetic average (UPGMA) and principle coordinate analysis (PCoA). Furthermore, in the UPGMA and PCoA, germplasms collected from the same or relatively similar geographic origin were closer. These findings are critical for developing conservation policies, facilitating evolutionary research, sustainable utilization and commercial cultivation of this pharmacologically important and threatened species.


Cytochemical investigations on the localization of 5'-nucleotidase in the rat hippocampus with special reference to synaptic regions.
The fine structural localization of the 5'-nucleotidase was investigated in the CA3 region of the rat hippocampus. The attention was focussed on the occurrence of the enzyme in the synaptic region. The 5'-nucleotidase activity was demonstrated at the surface membranes of axons and dendrites. Prominent portions of enzyme activity were detectable in the nuclei and the nuclear envelope, whereas the cytoplasmic organelles were nearly devoid of reaction product. In synapses five types of 5'-nucleotidase localization were revealed. A participation of the enzyme in the process of neurotransmission is discussed.


Interpretation of the variability of levels of regional background aerosols in the Western Mediterranean.
Results on interpretation of the variability of regional background PM levels in the Western Mediterranean basin (WMB) are presented. Mean PM levels recorded at Montseny, MSY (North-Eastern Spain) in the 2002--2007 period reached 17, 13 and 11 microg/m3 of PM10, PM2.5 and PM1, respectively. The daily evolution of PM levels is regulated by the breeze circulation (mountain and sea breezes). PM levels are lower at the rural sites at night owing to the nocturnal drainage flows and to the lowering of the mixing layer height below the MSY high. These nocturnal low levels allowed us to estimate the continental background PM levels. At midday, the atmospheric pollutants accumulated in the pre-coastal depression are transported upwards by the breeze, increasing PM levels. Maximum PM10 levels were recorded in summer, and February--March and November, and minimum values in the rest of the year coinciding with the highest frequency of Atlantic advection. PM peak episodes attributed to Saharan dust outbreaks were recorded in summer and February-March. In addition, anticyclonic situations (February--March and November) may impact in elevated rural areas by increasing hourly levels of PM1 up to 75 microg/m3. This scenario induces the stagnation of pollutants in the pre-coastal depression. Solar radiation activates mountain winds, transporting polluted air masses from the valleys to elevated areas resulting in an increase of fine PM levels in areas outside the boundary layer. A significant decrease in PM annual means (40% and 34% for the entire monitoring period, 7 microgPM10/m3 and 5 microgPM2.5/m3) was recorded at MSY between 2002 and 2007. There appears to be no single cause behind these trends. This could partially be ascribed to the varying frequency and intensity of Saharan dust episodes, but also to large-scale meteorological processes or cycles, and/or to local or meso-scale processes such as nearby anthropogenic emission sources.


Possible "outbreak" of Kawasaki disease in Victoria.
Kawasaki disease, a multisystem disorder of unknown cause, which primarily affects young children, has been recognized in many countries and previously reported in Melbourne. The condition is usually endemic, but has occasionally been reported in clusters or epidemics. Such an apparent "epidemic" occurred in the winter of 1981. This paper highlights the clinical features, the results of investigations and sequelae of this disorder in the seven children admitted to the Royal Children's Hospital, Melbourne, during that period. Possible aetiological factors were sought, but none was found.


The value of transurethral sonography in tumours of the urinary bladder.
The authors report on their first experience obtained in the field of transurethral sonography in cases of tumours of the urinary bladder. Sonography is a method without complication and risks. TNM classification of urinary bladder tumours is possible. A special advantage of this method of investigation is that sonography can be performed directly before transurethral tumour resection. Moreover, during the postoperative period, sonography can be combined with any kind of control cystoscopic investigation. The determination of the depth of infiltration and extension of the tumour is a prerequisite of therapeutic procedures in cases of cancer of the bladder.


Cell-specific transgene expression from a widely transcribed promoter using Cre/lox in mice.
Mice carrying two or more transgenes are used frequently to evaluate oncogene interactions during carcinogenesis. However, neoplastic transformation typically results in reduced expression both of differentiation-specific genes and of transgenes that use their promoters. In contrast, the more widely expressed metallothionein (MT) gene remains expressed at a high level in certain neoplasms, including those developing in pancreas. We have developed a system to maintain high-level, tissue-specific transgene expression during pancreatic carcinogenesis that uses Cre recombinase and a lox site-containing target transgene. Cre was expressed in pancreatic acinar cells under control of the elastase promoter (EL). Cre-mediated target transgene recombination placed a previously silent open-reading frame, encoding rat transforming growth factor alpha (TGFalpha), under control of the MT gene promoter. As long as DNA rearrangement does not occur in other cell types that express MT, TGFalpha expression will be restricted to acinar cells. Development of an effective target transgenic mouse required evaluation of multiple lineages to identify one with sufficient TGFalpha expression to induce pancreatic lesions after transgene rearrangement.


Use of duck embryo cell cultures for the study of arbovirus reproduction.
Duck embryo cell (DEC) cultures were used for the study of arbovirus reproduction. High sensitivity of DEC cultures to Japanese encephalitis, West Nile, Tyuleniy, Sakhalin and Baku viruses was established. DEC cultures are recommended for investigation of arbovirus reproduction.


Evidence for the existence of a novel enzyme system. myo-Inositol-1-phosphate dehydrogenase in Phaseolus aureus.
A novel enzyme system, myo-inositol-1-phosphate dehydrogenase, has been isolated from germinating mung bean seeds. The dehydrogenation and cleavage of myo-inositol 1-phosphate by this enzyme leads to the synthesis of a pentose phosphate which appears to be ribulose 5-phosphate. The pH optimum of the enzyme is 8.6; NAD+ is required as coenzyme and no other nucleotides can replace NAD+. Mono- or divalent cations are not essential for the enzyme activity. Stoichiometry of the reaction suggests that 2 mol of NAD+ are reduced per mol of ribulose-5-P generated.


Performance of three walking orthoses for the paralysed: a case study using gait analysis.
Three types of walking orthosis are currently available to enable paralysed people to achieve reciprocal gait. This case study assesses the performance in walking of one patient who was proficient in the use of all three devices. The results of a biomechanical analysis are presented in which comparisons are made between the orthoses in terms of general gait parameters and movement of the lower limbs and pelvis.


Serum levels of beta-trace protein and glomerular filtration rate--preliminary results.
The aim of this study was to evaluate the relationship between serum levels of beta-trace protein (BTP), a low molecular weight (MW) protein, and glomerular filtration rate (GFR). GFR and serum levels of BTP, and for comparison creatinine (Creat), cystatin C (Cys) and beta 2-microglobulin (beta 2M), were measured in 60 patients, with renal function ranging from normality to advanced renal failure. Serum levels of BTP progressively increased with the reduction of GFR. A good correlation was found between GFR and serum levels of BTP (r=0.918), Creat (r=0.932), Cys (r=0.937), and beta 2M (r=0.924). Furthermore, no statistically significant difference was found between BTP and Creat, Cys, beta 2M, as indicators of a moderate GFR impairment. These preliminary data indicate that BTP might be suitable as an indicator of GFR.


Changing association between schooling levels and HIV-1 infection over 11 years in a rural population cohort in south-west Uganda.
Previous studies have found that in Africa, a greater risk of HIV infection is often found in groups with higher educational attainment. However, some serial cross-sectional studies have found greater reductions in HIV prevalence among more educated groups, especially in cohorts of young adults. More recent studies have found some instances where higher schooling levels are associated with lower HIV prevalence. We describe changes in the association between schooling levels, HIV prevalence and condom use in a rural population-based cohort between 1989/1990 and 1999/2000, in Masaka District, Uganda. In 1989-1990, higher educational attainment was associated with higher risk of HIV-1 infection, especially among males, but once odds ratios are adjusted for age, no significant relation between schooling and HIV infection remains. In 1999-2000, there is, for females aged 18-29 years, a significant relationship between higher educational attainment and lower HIV prevalence, even after adjustment for age, gender, marital status and wealth (P for trend 0.01). Tests for interaction, significant for males and both genders combined, show that more schooling has been shifting towards an association with less HIV infection between 1989-1990 and 1999-2000, especially for young individuals. Condom use increased during the study period and this increase has been concentrated among more educated individuals. These findings suggest that over a decade more educated young adults, especially females, have become more likely to respond to HIV/AIDS information and prevention campaigns by effectively reducing their sexual risk behaviour.


SAPHO syndrome.
SAPHO syndrome is a disorder characterized by Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis. As the osteoarticular and skin manifestations often do not occur simultaneously and there are no validated diagnostic criteria, the diagnosis can be difficult. Clinical and imaging investigation is necessary to establish the many differential diagnoses of SAPHO syndrome. The etiopathogenesis involves infectious (probably Propionibacterium acnes), immunologic, and genetic factors. Treatment is based on information gathered from case reports and small series, and is related to specific skin or articular symptoms.


Hsa-miR-503-5p regulates CTDSPL to accelerate cisplatin resistance and angiogenesis of lung adenocarcinoma cells.
The study aimed to assess the role of hsa-miR-503-5p in cisplatin resistance and angiogenesis in LUAD and its underlying mechanisms. Hsa-miR-503-5p expression in LUAD and the target gene downstream of hsa-miR-503-5p was predicted by bioinformatics analysis. Binding relationship between the two genes was verified by dual-luciferase reporter assay. qRT-PCR was conducted for detecting gene expression in cells, CCK-8 for IC50 value, angiogenesis assay for human umbilical vein endothelial cell (HUVEC) angiogenic ability, flow cytometry for apoptosis ability, transwell assay for migration ability, and western blot for detecting the protein expression of vascular endothelial growth factor receptor 1 (VEGFR1), VEGFR2, and CTD small phosphatase like (CTDSPL). The results showed that hsa-miR-503-5p showed high expression, while its target gene CTDSPL presented decreased expression in LUAD. Hsa-miR-503-5p also had high expression in cisplatin-resistant LUAD cells. Knockdown of hsa-miR-503-5p resensitized LUAD cells to cisplatin, inhibited angiogenesis of drug-resistant cells, and reduced the protein expression of VEGFR1, VEGFR2, and EMT-related targets in cisplatin-resistant LUAD cells, but promoted the apoptosis ability. Hsa-miR-503-5p bound to CTDSPL gene and promoted cisplatin resistance and malignant progression of LUAD cells by negatively regulating CTDSPL. Our results revealed that hsa-miR-503-5p and CTDSPL may be novel targets for overcoming cisplatin resistance in LUAD.


Experimental versus predicted affinities for ligand binding to estrogen receptor: iterative selection and rescoring of docked poses systematically improves the correlation.
The computational determination of binding modes for a ligand into a protein receptor is much more successful than the prediction of relative binding affinities (RBAs) for a set of ligands. Here we consider the binding of a set of 26 synthetic A-CD ligands into the estrogen receptor ERα. We show that the MOE default scoring function (London dG) used to rank the docked poses leads to a negligible correlation with experimental RBAs. However, switching to an energy-based scoring function, using a multiple linear regression to fit experimental RBAs, selecting top-ranked poses and then iteratively repeating this process leads to exponential convergence in 4-7 iterations and a very strong correlation. The method is robust, as shown by various validation tests. This approach may be of general use in improving the quality of predicted binding affinities.


Effects of age, size and season on cryotolerance of dog semen - A retrospective analysis.
In a retrospective analysis of 508 ejaculates from 297 dogs, efficiency of semen cryopreservation and effects of age, season and dog size on characteristics of fresh and cryopreserved semen were evaluated. Volume of the sperm-rich ejaculate fraction increased to 10 years of age, decreased in 10 and 11-year old dogs (P < 0.001) but did not differ among seasons. Total sperm count was less in 10 and 11-year-old dogs (P < 0.001). The percentage of progressively motile, membrane-intact and morphologically normal spermatozoa before cryopreservation was least in 10 and 11-year-old dogs (P < 0.001). Cryopreservation resulted in less progressively motile spermatozoa (P < 0.001) with this being most pronounced in 10 and 11-year-old dogs (cryopreservation x age P = 0.004). The cryopreservation-induced decrease in morphologically normal spermatozoa (P < 0.001) was not affected by dog body weight. Number of cryopreserved AI doses differed among age groups (P < 0.001) and was less in 10 and 11-year-old dogs (median 1.5) compared with younger dogs (6-7 years, median 4.3). When ejaculates were grouped by a threshold of ≥ 35% progressively motile spermatozoa after freezing-thawing, 86.5% of all ejaculates were greater the threshold but this percentage decreased to 66% in 10 and 11-year-old dogs (P < 0.001). In conclusion, sperm cryotolerance is consistent for much of a dog´s lifespan but decreases after a certain age. Dog semen can be cryopreserved successfully throughout the year. Post-thaw semen characteristics were not different among cryopreserved ejaculates obtained from dogs differing in body weight.


[Reversibility of frailty in elderly patients thanks to a multicomponent training programme].
A retrospective study was conducted to evaluate the effects of a multi-component training program with strength machines on physical performance and reversibility of frailty in elderly people. At the end of the program, a significant increase in physical performance was observed and there was a significant decrease in frailty.