Historical aspects of studies on roles of the inflammasome in the pathogenesis of periodontal diseases.
The proinflammatory cytokine interleukin-1β (IL-1β) is produced as inactive proIL-1β and then processed by caspase-1 to become active. In 2002, it was demonstrated that the intracellular multiprotein complex known as the inflammasome functions as a molecular platform to trigger activation of caspase-1. Inflammasomes are known to function as intracellular sensors for a broad spectrum of various pathogen-associated and damage-associated molecular patterns. In 1985, it was demonstrated that Porphyromonas gingivalis, a representative bacterium causing chronic periodontitis, induces IL-1 production by murine peritoneal macrophages. Since then, many studies have suggested that IL-1, particularly IL-1β plays key roles in the pathogenesis of periodontal diseases. However, the term "inflammasome" was not used until the involvement of inflammasomes in periodontal disease was suggested in 2009. Several subsequent studies on the roles of the inflammasome in the pathogenesis of periodontal diseases have been published. Interestingly, two contradictory reports on the modulation of inflammasomes by P. gingivalis have been published. Some papers have described how P. gingivalis activates the inflammasome to produce IL-1β whereas some stated that P. gingivalis inhibits inflammasome activation to subvert immune responses. Several lines of evidence have suggested that the inflammasome activation is modulated by periodontopathic bacteria other than P. gingivalis. Hence, studies on the roles of inflammasomes in the pathogenesis of periodontal diseases began only 8 years ago and many pathological roles of inflammasomes remain to be clarified.


Radiographic evaluation of the bicipital groove morphology does not predict intraarticular changes in the long head of biceps tendon.
This study aimed to examine the clinical utility of the radiographic evaluation of the bicipital groove in predicting long head of biceps tendon (LHBT) pathology. A prospective study was conducted, and sixty consecutive patients proposed to shoulder arthroscopic surgery were selected. Before surgery, a radiographic evaluation was performed with a supine and a Fisk radiograph. Most supine radiographs (>75%) were non-interpretable and were excluded from the study. As some Fisk radiographs (26.7%) were also non-interpretable, that left 44 interpretable radiographs in the study. These were measured for medial opening angle, total opening angle, width and depth of the bicipital groove. The radiographic measurements and the presence of LHBT pathology, as assessed at arthroscopy, were correlated. Radiographic evaluation of the bicipital groove showed a mean medial opening angle of 53 ± 15° (23-90), a mean total opening angle of 80 ± 26° (30-135), a mean width of 10.3 ± 2.5 mm (6-19) and a mean depth of 4.1 ± 1.5 mm (1-8). Men had higher medial opening angle (60 vs 50°, p = 0.044) and wider grooves (11.9 vs 9.7 mm, p = 0.019). Twenty-five patients (56.8%) were found to have an abnormal LHBT. No correlation was found between the radiographic measurements and LHBT pathology. Only age was correlated with a LHBT lesion (61.8 vs 46.3 years, p < 0.001). Our results show that there is no correlation between radiographic morphologic evaluation of the bicipital groove and LHBT pathology.


Virus infection in remnant native bunchgrasses from invaded California grasslands.
This study examined the effects of infection with barley and cereal yellow dwarf viruses (BYDVs) on wild grass species in California, a region in which native perennial bunchgrasses have been largely replaced by exotic annual grasses. We sought to determine whether these widespread viruses compromise the fitness of wild hosts and thus have the potential to influence grassland dynamics. Plant viruses have been long overlooked in ecological studies, and their influence on wild hosts has often been assumed to be minimal. We examined the short-term and long-term consequences of infection on field-grown individuals from 18 different populations of wild California grasses (from seven native and one exotic species). Barley yellow dwarf virus infection was aggressive in most hosts and markedly impaired host fitness by reducing growth, survivorship, and fecundity. Previous work indicates that the presence of exotic grasses can more than double BYDV incidence in natives. Given the ubiquity of BYDVs, our results suggest that apparent competition and other virus-mediated processes may influence interactions among native and exotic grasses and potentially contribute to shifts in grassland community composition.


Sensory Ataxic Guillain-Barré Syndrome with Dysgeusia after mRNA COVID-19 Vaccination.
Guillain-Barré syndrome (GBS) has occasionally occurred in people who have received coronavirus disease 2019 (COVID-19) vaccines. Dysgeusia is rare symptom of GBS. We herein report a rare case of sensory ataxic GBS with dysgeusia just after the second dose of the Pfizer-BioNTech COVID-19 vaccine. Although autoantibodies against glycolipids were not detected, immunotherapy with intravenous immunoglobulin and methylprednisolone pulse therapy effectively ameliorated the symptoms. Our report suggests that the COVID-19 vaccine may induce various clinical subtypes of GBS, including a rare variant with sensory ataxia and dysgeusia.


The effect of swimming and type of stroke on bone metabolism in competitive adolescent swimmers: a pilot study.
Physical activity plays a key role in increasing and preserving bone mineral density (BMD). Effects on bone development associated with various nonweight-bearing sporting activities, such as swimming, are controversial. Different strokes used in swimming may also present as another factor. The aim of this study was to evaluate the effect of swimming and type of stroke on BMD in competitive adolescent athletes. Seventy-nine swimmers between the ages of 10 and 21 years participated in this study. BMD was measured with dual-energy X-ray absorptiometry at the lumbar vertebrae and left proximal femur. Daily calorie intake and calcium consumption, and measurements of calcium, phosphorus, alkaline phosphates, 25-hydroxyvitamin D (25(OH) D), and osteocalcin were evaluated. Preliminary results revealed that the type of stroke had no effect on BMD (P = 0.79). Additionally competitive swimmers did not have augmented bone mineral accretion, and in 13.9% of athletes low BMD was confirmed. Sixty percent of swimmers had either deficient or insufficient 25(OH) D levels and a low mean calorie (P = 0.542) and calcium (P = 0.038) intake was observed. This was the first study to evaluate the effect of swimming stroke on BMD. Although no effect was statistically shown, further studies with a larger series may determine this effect.


Forensic dental identification in complicated fractured skull conditions: case report with adapted algorithm for image comparison.
To analyze the perspective of using an adapted algorithm for digital images comparison while providing forensic dental identification in complicated fractured skull conditions by ante-mortem and post-mortem radiographical data sets. Ante-mortem orthopantomogram and post-mortem peri-apical X-ray images were converted in *.jpeg format with their further import into GIMP 2.10 software (The GIMP Development Team). Segmentation of OPG-image was provided in topographical projections of jaw segments obtained directly from the victim. Comparison of analyzed image segments was provided manually within GIMP 2.10 software using functions of "Layers" and "Opacity" through the proposed algorithm. Considering the fact that 20 positive concordant dental identifiers overall were verified during comparison of AM and PM X-ray datasets, we can conclude that odontological identity was established. All above-mentioned discrepancies could be classified as explainable. Inter-agreement rate between two investigators considering correspondence between AM and PM datasets reached Cohen's kappa level which is equal to 0,97, while positive 100% agreement was reached considering 21 out of 24 analyzed characteristics. Available AM and PM radiographical datasets represent a sufficient information for effective forensic dental identification, even if such were obtained by different roentgenological techniques (orthopantomography and periapical radiography). Using of an adapted algorithm for digital images comparison with forensic dental purposes could potentially overcome cognitive bias and observer's effect, speed up the process of analysis and increase the accuracy and inter-agreement rate while referencing AM and PM datasets.


Quantitative measurements of adsorbate-adsorbate interactions at solid-liquid interfaces.
The interactions between adsorbates at a solid-liquid interface were studied by video-rate STM for the case of sulfur on Cu(100) electrode surfaces in HCl solution. Quantitative data were obtained by analyzing the S(ad) dimer dynamics within the surrounding c(2 x 2)-Cl adlattice as well as the adsorbate configurations. The interactions are repulsive for S(ad) separated by one or two lattice spacings and attractive at a separation of square root of 2 with energies comparable to adsorbates at the solid-vacuum interface. The S(ad) diffusion barriers are significantly reduced in the vicinity of a neighboring adsorbate.


Elevated troponin T concentrations in critically ill patients.
To determine the incidence of troponin T elevations among a selected group of critically ill patients, to correlate these findings to electrocardiographs, and to compare troponin T-positive and T-negative patients in relation to clinical parameters. Prospective study. Mixed surgical and medical intensive care unit. Thirty-four consecutive critically ill patients who were mechanically ventilated or underwent thoracic or vascular surgery. Blood samples were collected at admission, the next morning, and 24 h after the second blood sampling. These samples were used for troponin T measurement and electrocardiographs were made when troponin T levels were elevated. Eleven of 34 patients (32%) had elevated troponin T levels, which were already present upon admission in eight out of 11 patients (73%). Most patients underwent surgery prior to ICU admission (21 of 34 patients). Significantly ( P=0.0055) more troponin T-positive patients underwent acute surgery, and significantly more ( P=0.045) troponin T-positive patients suffered from hypotension. Only four of the troponin T-positive patients were diagnosed as suffering from an acute myocardial infarction based on electrocardiographs. All troponin T-positive patients had coronary artery disease: nine had a history of CAD and two had actual CAD. No difference in mortality rates was observed between troponin T-positive and T-negative patients. An unexpectedly high percentage of included patients had troponin T elevations, which could be corroborated by electrocardiographs in only four cases suggesting that a high percentage of critically ill patients with a history of CAD suffer from clinically unrecognised (minor) myocardial damage.


Response in taste circuitry is not modulated by hunger and satiety in women remitted from bulimia nervosa.
Individuals with bulimia nervosa (BN) engage in episodes of binge eating, marked by loss of control and eating despite fullness. Does altered reward and metabolic state contribute to BN pathophysiology? Normally, hunger increases (and satiety decreases) reward salience to regulate eating. We investigated whether BN is associated with an abnormal response in a neural circuit involved in translating taste signals into motivated behavior, when hungry and fed. Twenty-six women remitted from BN (RBN) and 22 control women (CW) were administered water and sucrose during 2 counterbalanced fMRI visits, following a 16-hr fast or a standardized breakfast. Significant Group × Condition interactions were found in the left putamen, insula, and amygdala. Post hoc analyses revealed CW were significantly more responsive to taste stimuli when hungry versus fed in the left putamen and amygdala. In contrast, RBN response did not differ between conditions. Further, RBN had greater activation in the left amygdala compared with CW when fed. Findings suggest that RBN neural response to rewarding stimuli may not be modulated by metabolic state. Data raise the possibility that disinhibited eating in BN could result from a failure to devalue food reward when fed, resulting in an exaggerated response. (PsycINFO Database Record


Wetting properties of a hard-spherocylinder fluid on a substrate.
A density-functional theory is used to analyze the wetting properties of a fluid made up of hard spherocylinders of a length-to-breadth ratio L/D=5 on a model substrate. The substrate imposes an exclusion boundary condition over the molecular centres of mass, while at the same time favoring a definite molecular orientation, either parallel or perpendicular to the substrate, in a region next to the substrate. The wetting properties of this system are seen to depend on the strength with which the substrate orients the molecules: as the latter is increased, wetting by nematic phase is followed by a region of partial wetting which then leads to reentrant wetting by nematic. The two wetting transitions correspond to wetting films with nematic director perpendicular and parallel to the substrate, respectively. Also, in the region of partial wetting, an anchoring transition occurs in the substrate-nematic interface between two different director configurations (parallel and perpendicular to the substrate). Finally, a metastable wetting transition by isotropic is also obtained. This model considerably enriches the wetting phenomenology of the hard-spherocylinder fluid on substrates, of which only the pure hard wall, with no surface control parameter available, has been considered so far.


Descriptive information about Crohn disease: content analysis of patient education brochures.
Although providing necessary information to patients with Crohn disease (CD) can influence their quality of life, there has been no study regarding the information provided by healthcare providers to CD patients. The aim of our study was to describe the contents of brochures given to CD patients in Japanese hospitals. These brochures were compared with ones used in the United States, Canada, and the United Kingdom. Forty-nine members of the research group on inflammatory bowel disease in Japan were asked to answer a questionnaire regarding educational brochures for CD patients. We obtained 15 Japanese and three foreign brochures and conducted content analyses for seven global brochures. We received 34 replies. Only 15 (44%) of 34 hospitals gave the brochures to all newly diagnosed CD patients. In the Japanese brochures, a lot of content was devoted to nutrition therapy and self-management in terms of diet. On the contrary, foreign brochures devoted more content to symptoms and drug therapy. The existing approaches for providing information in Japanese hospitals were unsatisfactory. Furthermore, Japanese educational brochures for CD patients emphasized nutritional therapy and dietary restriction. This reflected the differences in treatment strategies among countries.


DNA-Driven Two-Layer Core-Satellite Gold Nanostructures for Ultrasensitive MicroRNA Detection in Living Cells.
It is a significant challenge to achieve controllable self-assembly of superstructures for biological applications in living cells. Here, a two-layer core-satellite assembly is driven by a Y-DNA, which is designed with three nucleotide chains that hybridized through complementary sequences. The two-layer core-satellite nanostructure (C30 S5 S10 NS) is constructed using 30 nm gold nanoparticles (Au NPs) as the core, 5 nm Au NPs as the first satellite layer, and 10 nm Au NPs as the second satellite layer, resulting in a very strong circular dichroism (CD) and surface-enhanced Raman scattering. After optimization, the yield is up to 85%, and produces a g-factor of 0.16 × 10-2 . The hybridization of the target microRNA (miRNA) with the molecular probe causes a significant drop in the CD and Raman signals, and this phenomenon is used to detect the miRNA in living cells. The CD signal has a good linear range of 0.011-20.94 amol ngRNA-1 and a limit of detection (LOD) of 0.0051 amol ngRNA-1 , while Raman signal with the range of 0.052-34.98 amol ngRNA-1 and an LOD of 2.81 × 10-2 amol ngRNA-1 . This innovative dual-signal method can be used to quantify biomolecules in living cells, opening the way for ultrasensitive, highly accurate, and reliable diagnoses of clinical diseases.


[Dynamic tests in females with Kallmann syndrome].
Three patients with Kallmann's syndrome (one of whom had undergone eight-year therapy with sex steroids) were studied with many dynamic tests. The progesterone and clomiphene tests were negative. An insulin test and TRH stimulation test showed a normal pool of GH and TSH in the hypophysis. A double stimulation with 100 micrograms LH-RH led to an inadequate gonadotropin response with a dominant FSH secretion, while the patient who had previously received sex steroids gave better results. The other two patients received 100 micrograms LH-RH i.m. daily for 20 days and the double LH-RH stimulation test was repeated. A satisfactory gonadotropin response with a predominance of LH secretion was noted. A TRH stimulation test revealed normal PRL secretion, while after a chlorpromazine test only one patient showed a satisfactory PRL secretion. Under combined HMG-HCG therapy, one of the patients conceived and had a normal outcome of her pregnancy.


High Dose Ascorbate Causes Both Genotoxic and Metabolic Stress in Glioma Cells.
We have previously shown that exposure to high dose ascorbate causes double stranded breaks (DSBs) and a build-up in S-phase in glioblastoma (GBM) cell lines. Here we investigated whether or not this was due to genotoxic stress as well as metabolic stress generated by exposure to high dose ascorbate, radiation, ascorbate plus radiation and H₂O₂ in established and primary GBM cell lines. Genotoxic stress was measured as phosphorylation of the variant histone protein, H2AX, 8-oxo-7,8-dihydroguanine (8OH-dG) positive cells and cells with comet tails. Metabolic stress was measured as a decrease in NADH flux, mitochondrial membrane potential (by CMXRos), ATP levels (by ATP luminescence) and mitochondrial superoxide production (by mitoSOX). High dose ascorbate, ascorbate plus radiation, and H₂O₂ treatments induced both genotoxic and metabolic stress. Exposure to high dose ascorbate blocked DNA synthesis in both DNA damaged and undamaged cell of ascorbate sensitive GBM cell lines. H₂O₂ treatment blocked DNA synthesis in all cell lines with and without DNA damage. DNA synthesis arrest in cells with damaged DNA is likely due to both genotoxic and metabolic stress. However, arrest in DNA synthesis in cells with undamaged DNA is likely due to oxidative damage to components of the mitochondrial energy metabolism pathway.


Memory complaints in mild cognitive impairment, worried well, and semantic dementia patients.
Complaints related to memory are characteristic of normal ageing, affective disorders, and are a cardinal feature of amnestic mild cognitive impairment (aMCI), the proposed prodrome to Alzheimer disease proper. The aim of this study was to investigate the profile of subjective memory complaints in different cognitive syndromes. Subjective memory was assessed using the Cambridge Memory Complaints Questionnaire consisting of 20 questions about everyday aspects of memory. This was completed by 22 "worried well" (WW), 85 aMCI, and 40 semantic dementia (SD) patients at first presentation to a memory clinic. All patients were followed up for 2 years. A principal component factor analysis revealed 5 principal factors pertaining to working, episodic, topographical, and semantic memory. All factors, except topographical memory, reliably differentiated SD patients from other groups, with aMCI and WW patients complaining significantly more about working and episodic memory, and SD patients complaining significantly more about semantic memory. WW and aMCI patients, however, could not be differentiated, even those aMCI patients who progressed to dementia. Memory complaints are strikingly similar to the description of typical core deficits in SD patients. The sole reliance on memory complaints for insight into memory functioning and diagnosing aMCI is problematic.


Increased immunoreactive plasma and urinary growth hormone in growth retardation with defective generation of somatomedin a (Laron's Syndrome).
In a boy 4 years old with clinical hypopituitary dwarfism, high plasma and urinary levels of immunoreactive growth hormone were found. Somatomedin A levels in serum were low and failed to respond after short-term treatment with human growth hormone. The parents were first cousins. In the arginine and insulin tolerance tests the initially high immunoreactive growth hormone levels were later followed by a decrease to high normal values. Insulinopenic response was present during the arginine and glucose tolerance tests. As a growth hormone molecule defect is not found in these patients and no growth or other metabolic response to exogenous HGH can be demonstrated, it is concluded that a defective somatomedin generation may be present, probably in conjunction with a generalized receptor defect and deficient feedback system with abnormal release of HGH. The lack of somatomedin A is responsible for the severe growth retardation and the disturbance in carbohydrate metabolism is probably caused by sustained high growth hormone levels.


Dietary Advanced Glycation End Products: Their Role in the Insulin Resistance of Aging.
Insulin resistance (IR) is commonly observed during aging and is at the root of many of the chronic nontransmissible diseases experienced as people grow older. Many factors may play a role in causing IR, but diet is undoubtedly an important one. Whether it is total caloric intake or specific components of the diet, the factors responsible remain to be confirmed. Of the many dietary influences that may play a role in aging-related decreased insulin sensitivity, advanced glycation end products (AGEs) appear particularly important. Herein, we have reviewed in detail in vitro, animal, and human evidence linking dietary AGEs contributing to the bodily burden of AGEs with the development of IR. We conclude that numerous small clinical trials assessing the effect of dietary AGE intake in combination with strong evidence in many animal studies strongly suggest that reducing dietary AGE intake is associated with improved IR in a variety of disease conditions. Reducing AGE content of common foods by simple changes in culinary techniques is a feasible, safe, and easily applicable intervention in both health and disease. Large-scale clinical trials are still needed to provide broader evidence for the deleterious role of dietary AGEs in chronic disease.


Challenges in the treatment of melanoma with BRAF and MEK inhibitors in patients with sickle cell disease: case report and review of the literature.
Patients with sickle cell disease (SCD) suffer from complications due to anemia, inflammation, and vaso-occlusion. Factors that trigger sickling and/or inflammation may initiate such complications, while treatment with hydroxyurea (HU) reduces their emergence and prolongs survival. On the contrary, inhibition of the BRAF-MEK-ERK pathway with BRAF and MEK inhibitors (BRAF/MEKi) has revolutionized treatment of melanoma but their use has been correlated with inflammatory adverse events. Thus, treatment of patients with SCD with BRAF/MEKi may be quite challenging and pyrexia in those patients should be managed as a medical emergency. In this article, intrigued by the case of a 36-year-old female patient with S/β-thal under HU who was treated with dabrafenib and trametinib for melanoma, we analyze the mechanisms underlying inflammation and vaso-occlusion in SCD, the mechanisms of pyrexia and inflammation induced by BRAF/MEKi, their potential interconnections, the shared role of the inflammasome in these two entities, and the protective effect of HU in SCD. Since SCD is the most common inheritable blood disorder, the administration of BRAF/MEKi for melanoma in patients with SCD may be a rather common challenge. Thus, proper treatment with HU may pave the way for an uneventful management of such patients.


[Retrovesical hydatid cyst in children: report of 3 cases].
Retrovesical hydatid cyst is rare, even in endemic regions. From a presentation of three cases, the authors will review the clinical findings and illustrate the imaging features of this pathology and relate diagnostic and therapeutic difficulties.


The interrelations between sexual orientation, sense of belonging and dysphoria among Australian women.
This research examined whether sense of belonging in the community and sexual orientation were associated with dysphoria among women. Australian female heterosexuals (n = 202) and lesbians (n = 184) completed the Sense of Belonging Instrument and the Depression, Anxiety, Stress Scales. Results indicated that lesbians experienced a decreased sense of belonging and more dysphoria compared with heterosexual women. Subsequent analyses indicated that sense of belonging to the community mediated the relation between sexual orientation and dysphoria. In addition, sexual orientation moderated the relation between sense of belonging and dysphoria. It appears that the enhancement of lesbians' sense of belonging in the community would be associated with a reduction in dysphoria.


Adverse Drug Events in Patients with Mental Disorder in an Ambulatory Setting.
Although adverse drug events (ADEs) among inpatients occur frequently and are widely studied, few data are available on ADEs among outpatients with mental disorders. To determine the rates, types, and severity of ADEs in patients with mental disorder. Cross-sectional survey of patients with mental disorder attending outpatient department. Data were collected over a period of 6 months. A total of 400 patients (217 schizophrenia patients, 127 bipolar affective disorder patients, and 56 patients of depression) with a mean age of 32.1 ± 9.7(±standard deviation) participated in the study. Patients suffering from schizophrenia and all nonadherent patients reported significantly more ADEs (P < 0.05). Out of 343 patients (86%) who reported at least one ADE, majority (87%) reported central nervous system ADEs followed by weight gain (48%), gastro-intestinal (28%), skin (4%), cardiovascular (1%), and sexual dysfunctions (0.3%). Out of 673 ADEs reported, sedation (41%) and weight gain (25%) were reported most commonly. Most ADEs reported (76%) were mild; however, there were no life-threatening, fatal, or serious ADEs. The medication classes most frequently involved in ADEs were antipsychotics (72%) followed by sedatives (44%), antimanic drugs (32%), and antidepressants (27%). Patients on atypical antipsychotic drugs reported significantly more body weight gain (P < 0.05). More than three drugs were prescribed in 49% of patients who reported ADEs. The study data indicate high prevalence of ADEs in the outpatients on psychotropic medications.


Impact of a reduced iodine load with deep learning reconstruction on abdominal MDCT.
To evaluate the impact of a reduced iodine load using deep learning reconstruction (DLR) on the hepatic parenchyma compared to conventional iterative reconstruction (hybrid IR) and its consequence on the radiation dose and image quality. This retrospective monocentric intraindividual comparison study included 66 patients explored at the portal phase using different multidetector computed tomography parameters: Group A, hybrid IR algorithm (hybrid IR) and a nonionic low-osmolality contrast agent (350 mgI/mL); Group B, DLR algorithm (DLR) and a nonionic iso-osmolality contrast agent (270 mgI/mL). We recorded the attenuation of the liver parenchyma, image quality, and radiation dose parameters. The mean hounsfield units (HU) value of the liver parenchyma was significantly lower in group B, at 105.9 ± 10.9 HU versus 118.5 ± 14.6 HU in group A. However, the 90%IC of mean liver attenuation in the group B (DLR) was between 100.8 HU and 109.3 HU. The signal-to-noise ratio of the liver parenchyma was significantly higher on DLR images, increasing by 56%. However, for both the contrast-to-noise ratio (CNR) and CNR liver/PV no statistical difference was found, even if the CNR liver/PV ratio was slightly higher for group A. The mean dose-length product and computed tomography dose index volume values were significantly lower with DLR, corresponding to a radiation dose reduction of 36% for the DLR. Using a DLR algorithm for abdominal multidetector computed tomography with a low iodine load can provide sufficient enhancement of the liver parenchyma up to 100 HU in addition to the advantages of a higher image quality, a better signal-to-noise ratio and a lower radiation dose.


Thrombolysis in recurrent lacunar stroke: a case example.
We report a case of intravenous thrombolysis in a patient with early recurrent stroke. A 62-year-old man recovered nearly completely after a lacunar infarct of the left putamen. He suffered stroke recurrence 7 days later due to a new infarct in the left internal capsule. Intravenous alteplase 0.9 mg/kg was administered 40 min after the symptom onset resulting in significant neurologic improvement. Intravenous thrombolysis may be safe for early recurrent lacunar stroke in patients with relatively small risk of hemorrhage.


Use of newer anticoagulants in patients with chronic kidney disease.
The current indications, dosing, and practical considerations for use of newer anticoagulants in patients with various degrees of renal impairment who do not require dialysis are reviewed. Kidney function should generally be evaluated in all patients commencing anticoagulant therapy. As in the general population, hospitalized patients with impaired renal function most often have impairment that is mild to moderate in severity. Drug dosing in patients with chronic kidney disease may require that adjustment be made to the usual loading or maintenance dose of a drug. Newer anticoagulants with labeling approved by the Food and Drug Administration for venous thromboembolism (VTE) prophylaxis, treatment, or both include the low-molecular-weight heparins (LMWHs) and the factor Xa inhibitor fondaparinux. Some LMWHs are also indicated for the management of patients with acute coronary syndrome (ACS). All of the newer anticoagulants currently available for the management of VTE and ACS have approved labeling for use in patients with mild-to-moderate renal impairment. Currently available LMWHs, factor Xa inhibitors, and direct thrombin inhibitors (excluding argatroban) are eliminated primarily by the kidneys, so dosing in patients with severe renal impairment may require cautious dosage reduction or increased monitoring for bleeding and thromboembolic complications or both. Unfractionated heparin is the preferred anticoagulant for use in most of these patients. Newer anticoagulants should be used with caution in patients with mild-to-moderate renal impairment. Unfractionated heparin remains the preferred anticoagulant in most patients with severe renal impairment even though its use is associated with increased bleeding in this population. Dosing of newer anticoagulants, except argatroban, requires cautious dosage reduction and increased monitoring for complications.


Assessment of cytological atypia, AgNOR and nuclear area in epithelial cells of normal oral mucosa exposed to toombak and smoking.
The purpose of this study was to assess cellular proliferative activity of clinically healthy oral mucosal epithelial cells of toombak dippers and smokers by means of AgNOR counts and nuclear areas via nuclear morphometry. Smears were collected from normal-appearing mouth floor mucosa and tongue of 75 toombak dippers, 75 smokers and 50 non-tobacco users between the ages of 20 and 70 with a mean age of 36 years. AgNORs were counted in the first 50 well-fixed, nucleated squamous cells and nuclear areas were calculated via microscopic stage micrometer. Cytological atypia was ascertained in 6 tobacco users and could not be ascertained in non-tobacco users. Statistically mean AgNOR numbers per nucleus in the non-tobacco users (2.45±0.30) was lower than the toombak dippers (3.081±0.39, p<0.004), and the smokers (2.715±0.39, p<0.02), and mean nuclear areas of epithelial cells of toombak dippers (6.081±0.39, p<0.009) and smokers (5.68±10.08, p<0.01) was also significantly higher than non-smokers (5.39±9.4). The mean number of nuclei having more than 3 AgNORs was 28%, 19% and 7% in toombak dippers, smokers and non-tobacco users, respectively. These findings support the view that toombak dipping and smoking are severe risk factors for oral mucosal proliferative lesions and exfoliative cytology is valid for screening of oral mucosal lesions.


Toxic chlorobiphenyls in adipose tissue and whole blood of an occupationally/accidentally exposed man and the general population.
Individual polychlorinated biphenyl (CB) congeners in adipose and whole blood tissues of a capacitor manufacture worker (occupational/accidental exposure) and of the general population were determined. Nondestructive sample cleanup and multidimensional gas chromatography-electron capture detection (MDGC-ECD) techniques were applied. Special attention was given to the toxicologically relevant congeners CB-77, CB-126, CB-169, CB-105, CB-114, CB-118, CB-156, CB-167, and CB-189 (IUPAC). Lipid-based tissue contents of sigma CBs were higher in the occupationally/accidentally exposed worker (adipose = 7,000 ng/g; whole blood = 11 ng/g) than in the general population (adipose = 300 ng/g; whole blood = 1.9 ng/g). Among the non-ortho Cl CBs, CB-77 was below detection limit (< 1.0 pg/g). The contents of CB-126 for the capacitor manufacture worker were 2,000 and 3 pg/g, and in the general population were 100 and 2 pg/g for adipose and whole blood, respectively. The corresponding data for CB-169 were 3,500 and 4 for adipose and whole blood, respectively, in the exposed worker, and 40 and 2 for adipose and whole blood, respectively, in the general population. Congeners with highest contents were CB-153, CB-138, CB-180, CB-170, and CB-187. These congeners possess chlorine substitution patterns, making them resistant to metabolism. X/153 ratios suggest that both PB and 3-MC type cytochrome P-450 enzymes were induced in the exposed worker, as well as in the general population.


Serological investigation of latex allergy in Argentina.
Atopy to latex has been reported in different high-risk groups of subjects in whom it is mainly caused by proteins from natural latex that are responsible for eliciting a variety of clinical symptoms, some of them systemic. Thus, identification of subjects sensitized to latex proteins is of great health importance, because it would become possible to advise them to avoid contact with latex-containing products. Protein extracts from ammoniated latex were prepared by incubation with PBS buffer either with or without detergents, followed by ultracentrifugation. Three immunoenzymic methods were developed (EAST, ELISA, and immunoblotting) to detect the presence of specific IgE antibodies against latex proteins in sera of patients from different groups at risk. The protein content of the latex extracts ranged from 5.3 to 8.8 mg/mL. The prevalence of specific IgE against latex proteins was 9/28 (32.1%) in children with multiple surgeries, 17/98 (17.3%) in health care workers, and 23/123 (18.6%) in outpatients assisted at the Allergy Department. None of the sera belonging to the healthy control group showed the presence of specific IgE. Therefore, this protein extract from latex could be used to detect specific IgE antibodies in serum by immunoenzymic methods. Serologic results for latex-specific IgE found are in accordance with those reported in the literature of other countries.


Effect of the flavonoid hesperidin on glucose and fructose transport, sucrase activity and glycaemic response to orange juice in a crossover trial on healthy volunteers.
Although polyphenols inhibit glucose absorption and transport in vitro, it is uncertain whether this activity is sufficient to attenuate glycaemic response in vivo. We examined this using orange juice, which contains high levels of hesperidin. We first used a combination of in vitro assays to evaluate the potential effect of hesperidin and other orange juice components on intestinal sugar absorption and then tested whether this translated to an effect in healthy volunteers. Hesperidin attenuated transfer of 14C-labelled glucose across differentiated Caco-2/TC7 cell monolayers. The involvement of the sugar transporter GLUT2 was demonstrated by experiments carried out in the absence of Na to exclude the contribution of sodium-glucose linked transporter 1 and further explored by the use of Xenopus laevis oocytes expressing human GLUT2 or GLUT5. Fructose transport was also affected by hesperidin partly by inhibition of GLUT5, while hesperidin, even at high concentration, did not inhibit rat intestinal sucrase activity. We conducted three separate crossover interventions, each on ten healthy volunteers using orange juice with different amounts of added hesperidin and water. The biggest difference in postprandial blood glucose between orange juice and control, containing equivalent amounts of glucose, fructose, sucrose, citric acid and ascorbate, was when the juice was diluted (ΔC max=-0·5 mm, P=0·0146). The effect was less pronounced when the juice was given at regular strength. Our data indicate that hesperidin can modulate postprandial glycaemic response of orange juice by partial inhibition of intestinal GLUT, but this depends on sugar and hesperidin concentrations.


Small-bowel bacterial overgrowth in the postgastrectomy syndrome.
Jejunal flora, bile acid deconjugation, and breath hydrogen (H2) and methane (CH4) excretion were studied in 22 Billroth II (BII)-operated patients with chronic postprandial symptoms, dumping (9), vomiting (7), pain (10), and diarrhoea (14). Sixteen were below 90% of desirable weight. Two control groups were included, one comprising 5 symptom-free, BII-operated volunteers and another comprising 12 healthy, unoperated volunteers. The numbers of bacteria recovered from jejunal secretions in the postgastrectomy patients did not differ significantly from those recovered in the symptom-free BII-operated controls but were significantly lower in the unoperated controls. Production of fermentation gas in anaerobic media supplemented with carbohydrates occurred in 17 of 22 postgastrectomy patients and in 4 of 5 BII-operated controls but in none of the unoperated controls. Bacterial bile acid deconjugating activity did not differ significantly between the postgastrectomy patients and the BII-operated controls but was significantly lower in the unoperated controls. Breath H2 excretion after glucose ingestion was significantly higher in the postgastrectomy patients than in both the BII-operated and the unoperated controls. The addition of pectin or guar gum to the glucose meal largely prevented postprandial symptoms and breath hydrogen excretion. Six out of 12 postgastrectomy patients treated with metronidazole recorded symptomatic effects, mainly on diarrhoea. Our findings indicate that jejunal bacterial overgrowth may be a major cause of the symptoms in some postgastrectomy patients. The tests available for demonstration of small-bowel bacterial overgrowth, perhaps with the exception of the glucose H2 breath test, did not differentiate satisfactorily between symptom-producing and non-symptom-producing abnormal jejunal flora. Thus these tests may seem to have a limited practical diagnostic value in such patients.


Radiographic and Functional Outcomes following Knee Arthrodesis Using the Wichita Fusion Nail.
The purpose of this study was to report both the radiographic and functional outcomes of patients undergoing knee arthrodesis with the Wichita Fusion Nail (WFN) within the Republic of Ireland and compare the results to existing literature. Patient charts and radiographs were reviewed on all patients who had a WFN implanted in Ireland to date. Patients were invited to complete a Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score as a functional assessment. Twenty-three patients were identified. Patients had an average of 8 (range: 0-26) knee surgeries prior to arthrodesis. The most common indication was failed arthroplasty due to recalcitrant infection (69.5%). Successful fusion occurred in 60.8% of patients. The mean time to fusion was 9.21 months. The mean WOMAC score was 58.55 with a range of 31 to 96. We found a rate of arthrodesis lower than that reported in other published series. However, the rate of major complications was comparable to those published previously, reflecting the often-challenging patient cohort. Our study shows that the WFN should not be viewed as a near-universally successful option to salvage an unreconstructable knee.


Comparison of polypropylene versus polyester mesh in the Lichtenstein hernia repair with respect to chronic pain and discomfort.
Inguinal hernias are the most common operative procedure performed by general surgeons, and tension-free mesh techniques have revolutionized the procedure. While hernia recurrence rates have decreased, chronic postoperative pain has become recognized more widely. New mesh products offer the potential to decrease pain without compromising recurrence rates. Polyester mesh is a softer material than traditional polypropylene and may offer the benefit of causing less postoperative pain and improved quality of life. Prospective, single-blind, randomized controlled trial involving 78 patients assigned to receive Lichtenstein type repair with either polyester (n = 39) or polypropylene (n = 39) mesh. Attempt was made to identify ilioinguinal, iliohypogastric, and genitofemoral nerves intraoperatively and document their handling. Patients were interviewed and examined preoperatively and postoperatively at 2 weeks and 3 months. Inguinal Pain Questionnaire (IPQ) and VAS scores were obtained and analyzed using two sample t test for continuous variables and Chi-square test for categorical variables. VAS scores at 3 months were 0.46 for the polyester group versus 0.56 for the polypropylene group (P = 0.6727). At 3 months, 82.3% of the polyester and 76.4% of the polypropylene group had VAS = 0 (P = 0.5486). There was no significant difference between the two groups' VAS scores at 3 months. IPQ did not show any difference between the two groups with the exception of "catching or pulling" being reported in 34.3% of polyester and 5.7% of polypropylene groups (P = 0.0028). Polyester mesh does not decrease the amount of chronic pain at 3 months. Outcomes with polyester mesh are comparable to polypropylene mesh for Lichtenstein inguinal hernia repair with regards to postoperative pain and quality of life. The sample size in this study was small and limits the significance of the results. Further studies are needed to find the optimal mesh for inguinal hernia repair.


Acute fatty liver of pregnancy associated with fetal mitochondrial trifunctional protein deficiency.
Acute fatty liver of pregnancy (AFLP) is a devastating disorder of the maternal liver in the third trimester. Recent studies have demonstrated an association between AFLP and fetal fatty acid oxidation disorders. Here, we report a case of AFLP caused by fetal mitochondrial trifunctional protein (TFP) deficiency. A 21-year-old parous woman presented with nausea, genital bleeding and abdominal pain at 33 weeks of gestation. Laboratory data revealed hepatic failure and disseminated intravascular coagulopathy. The patient underwent emergency cesarean section and was diagnosed with AFLP from the clinical characteristics. She was successfully treated with frequent plasma exchange. The newborn presented severe heart failure and died on the 39th day after birth. Tandem mass spectrometry indicated long-chain fatty acid oxidation disorder. Gene analysis demonstrated homozygous mutation in exon 13 of HADHB, the gene responsible for mitochondrial TFP deficiency. The parents carried a heterozygous mutation at the same location in HADHB.


The beta3-adrenergic agonist CL316,243 inhibits insulin signaling but not glucose uptake in primary human adipocytes.
Insulin resistance and obesity are central components of the metabolic syndrome which has become the leading cause of cardiovascular morbidity and mortality worldwide. Direct interactions of the beta (3)-adrenoceptor system with adipocyte signaling and function in humans remain poorly understood. However, this might have important consequences for the regulation of energy homeostasis and insulin resistance in states of hyperinsulinemia and sympatho-adrenergic overactivity. We therefore investigated beta (3)-adrenoceptor-mediated effects on insulin signaling and glucose uptake in mammary adipocytes of healthy women that underwent breast reduction surgery. Glucose uptake was strongly induced by insulin stimulation. This was paralleled by robust induction of insulin receptor kinase activity, insulin receptor substrate-1-associated phosphatidylinositol-3 kinase activity, and protein kinase B phosphorylation. Treatment with the beta (3)-adrenoceptor-selective agonist CL316,243 alone, neither induced alterations in the early insulin signaling cascade nor changed the basal level of glucose uptake. By contrast, pretreatment with the beta (3)-adrenoceptor agonist inhibited the insulin-induced insulin receptor substrate-1-associated phosphatidylinositol-3 kinase activity by 50 % and protein kinase B phosphorylation by 40 % without affecting insulin receptor kinase activity upstream. However, on the functional level insulin-induced glucose uptake remained unchanged by beta (3)-adrenoceptor stimulation. Our data demonstrate an insulin receptor-independent negative influence of beta (3)-adrenoceptor stimulation on proximal insulin signaling. This inhibition is apparently dissociated from glucose uptake in human adipocytes.


Urokinase-related proteins in human urine. Isolation and characterization of single-chain urokinase (pro-urokinase) and urokinase-inhibitor complex.
Urokinase-related proteins were purified from 60-liter batches of human urine collected into the protease inhibitor aprotinin to prevent proteolytic degradation. Three homogeneous species were obtained by chromatography on zinc chelate-Sepharose, SP-Sephadex C-50, Sephadex G-100, benzamidine-Sepharose, and immunoadsorption on a murine anti-human urokinase monoclonal antibody. One urokinase-related protein with Mr 95,000 representing a complex of two-chain urokinase with an inhibitor accounts for about 70% of the total urokinase-related antigen in urine. Nucleophilic agents dissociate the complex into active two-chain urokinase and a protein with Mr 45,000-50,000 which is immunologically distinct from urokinase. Approximately 25% of the urinary urokinase-related antigen represents a single-chain molecule with Mr 54,000. This highly purified single-chain molecule was obtained with a yield of 5 micrograms/liter of urine. Only trace amounts (less than 5%) of the urokinase-related antigen were recovered as free two-chain urokinase. The urinary single-chain urokinase-related protein has no specific affinity for fibrin. It has a very low activity on Pyroglu-Gly-Arg-p-nitroanilide, a urokinase-specific synthetic substrate, but directly activates plasminogen following Michaelis-Menten kinetics with Km = 0.7 microM and kcat = 0.0011 S-1. The single-chain molecule is rapidly converted to active two-chain urokinase by plasmin. Active two-chain urinary urokinase has a very high amidolytic activity and activates plasminogen with Km = 60 microM and kcat = 1.4 S-1. It is concluded that the urokinase-related proteins in human urine consist of about 25% of single-chain urokinase (10-20 micrograms/liter) and of about 75% two-chain urokinase (40-50 micrograms/liter), the bulk of which is complexed to an inhibitor. Because even in freshly voided urine most of the urokinase-related antigen is already converted to two-chain urokinase, urine does not seem to be a suitable source for the large-scale purification of single-chain urokinase. In view of the very significant intrinsic plasminogen-activating properties of single-chain urokinase, it should not be considered to be a proenzyme form of urokinase. The dramatic differences of its kinetic constants from those of urokinase render the designation single-chain urokinase equally inadequate. Consequently, the designation "single-chain urokinase-type plasminogen activator" was recently adopted by the International Committee on Thrombosis and Haemostasis (Annual Meeting, San Diego, CA, July 13-14, 1985).


[Transcatheter Treatment of Degenerative Critical Aortic Valve Stenosis in a Patient With Severe Heart Failure and Chronic Lymphocytic Leukemia].
Surgical aortic valve replacement is the standard therapy for severe aortic valve stenosis, however one third of patients are rejected because of high surgical risk. Under medical treatment alone these patients have a very poor prognosis with a high mortality rate. We present a case of 70-year-old male patient with degenerative symptomatic critical aortic stenosis and chronic lymphocytic leukemia. Due to recurrence.


Statistical theory of the polarization on the Poincaré sphere.
The random nature of light emitters requires that the theory to study polarization must adopt a statistical approach. Although the Stokes parameters are proposed in this sense, these are implemented as temporal averages, appealing to an ergodic hypothesis, without discussing which probability distributions are treated. Therefore, here the polarization dynamics on the Poincaré sphere of random light sources, whose phases and amplitudes of the electric fields are statistically independent, is described through the von Mises-Fisher distribution. This allows us to relate the degree of polarization and the normalized Stokes parameters with the concentration parameter and the mean direction of the von Mises-Fisher distribution. Also, it is found that their marginal distributions have the same statistical behavior as the Eliyahu-Brosseau distribution.


On the absorption capacity of the REDY cartridge.
The absorption capacity of the REDY cartridge was investigated exclusively by in vitro experiments. The maximum absorption capacity for urea, phosphate, creatinine, and urinc acid, was found to be respectively 55 g, more than 4 g (phosphorus), 10 g, and more than 7,5 g. The maximum absorption rates of the same substances were found to be 600-800 mg/min., more than 33 mg/min., more than 170 mg/min., and 13 mg/min. respectively. The ability of the cartridge to absorb urea was found to be practically unaffected by 2 mmol of copper and 7 mmol of zinc, and to be unaffected by supraphysiological concentrations of lithium. The amount of exchangeable cations was determined for three cartridges, and found to be 6100, 3800, and 7200 mmol. The cation exchanger was found to act as a buffer, giving the whole cartridge a buffering capacity of 0,6 mol. Of the layers of cation exchanger, anion exchanger, and activated charcoal, only the latter was found to be able to bind urea.


An Exploration of Child-Staff Interactions That Promote Physical Activity in Pre-School.
A previous study identified a significant association between the average physical activity levels of pre-school staff and children during pre-school hours but did not determine if this association was initiated by pre-school staff or children. The present study aimed to explore the interactions between children and staff to better understand the conditions of such a relationship. Observations using the Environment and Policy Assessment and Observation (EPAO) protocol were carried out in three pre-schools, and a focus-group interview and semiformal interviews were conducted with five pre-school staff in one of the three pre-schools to examine the research question. Both the observations and the interview data revealed that physical activity by pre-school staff initiated physical activity among the children. The findings pointing to the importance of pre-school staff as organizers of the physical activity of children and the willingness of staff to join a physical activity initiated by the children also appear to be important. The findings also indicate that most of the physical activity took place outdoors. The study highlights the importance of pre-school staff as major contributors to the physical activity of pre-school children.


High diopter spectacle using a flexible Fresnel lens with a combination of grooves.
In this study, the Fresnel lens was investigated as a potential candidate for vision correction in patients with myopia. A few previous studies have suggested this idea; however, Fresnel lenses are limited by their aesthetics and quality. Therefore, we designed a combination of Fresnel lens grooves with a constant height and pitch of 13 µm and 0.1 mm, respectively, to overcome the limitations caused by ultra-precision machining with a tool nose radius of 30 µm. A thin replicated Fresnel lens with a power of -5 diopter was procured and applied directly as spectacles that are unattached to the normal lens. The optical performance and image quality of the Fresnel lens were compared with those of a conventional lens possessing the same power in both near and far vision. These results extend the applicability for the use of Fresnel lenses as vision-correcting ophthalmological lenses and imaging systems.


Large magnetoelectric coupling in multiferroic oxide heterostructures assembled via epitaxial lift-off.
Epitaxial films may be released from growth substrates and transferred to structurally and chemically incompatible substrates, but epitaxial films of transition metal perovskite oxides have not been transferred to electroactive substrates for voltage control of their myriad functional properties. Here we demonstrate good strain transmission at the incoherent interface between a strain-released film of epitaxially grown ferromagnetic La0.7Sr0.3MnO3 and an electroactive substrate of ferroelectric 0.68Pb(Mg1/3Nb2/3)O3-0.32PbTiO3 in a different crystallographic orientation. Our strain-mediated magnetoelectric coupling compares well with respect to epitaxial heterostructures, where the epitaxy responsible for strong coupling can degrade film magnetization via strain and dislocations. Moreover, the electrical switching of magnetic anisotropy is repeatable and non-volatile. High-resolution magnetic vector maps reveal that micromagnetic behaviour is governed by electrically controlled strain and cracks in the film. Our demonstration should inspire others to control the physical/chemical properties in strain-released epitaxial oxide films by using electroactive substrates to impart strain via non-epitaxial interfaces.


The effect of instruction on control of blood pressure in individuals with essential hypertension.
This exploratory study examined the effect of structured teaching about essential hypertension on control of the diastolic blood pressure in individuals with a diagnosis of essential hypertension. Using the pre-test, post-test design, study participants were measured on knowledge about essential hypertension and diastolic blood pressure before and after intervention. Six hypotheses were tested, three related to control of blood pressure, and three related to knowledge about essential hypertension. There was no significant difference between the experimental and control groups on diastolic blood pressure readings at the conclusion of the study. There was a significant difference between the experimental and control groups on post-test scores on knowledge of essential hypertension. It was concluded that structured teaching had no significant effect upon control of the diastolic blood pressure. Instruction increased knowledge, but not blood pressure control.


Comparison of Nasalance scores obtained with the Nasometer 6200 and the Nasometer II 6400.
This study was designed to compare nasalance scores obtained with the old Nasometer 6200 and the new Nasometer II 6400, and to evaluate test-retest reliability of nasalance scores on each machine. Nasalance scores were obtained for 60 subjects reading each of two stimuli. Each subject read each stimulus two times on one machine; the headgear was removed and replaced and each stimulus was read a third time. The same procedure was then repeated with the second machine. Within machines, nasalance scores were compared for repeated stimuli with and without headgear change. The first reading of each stimulus with each machine was used to compare nasalance scores across machines. The subjects were 60 adults with normal speech ranging in age from 19 to 59 years. The main outcome measures were the 12 nasalance scores obtained for each of 60 subjects. For both passages, there was a significant difference in nasalance scores between the old Nasometer and the Nasometer II; however, the actual variability that could be attributed to a difference between machines was small. Most of the variability between machines could be explained as within-subject performance variability and variability associated with headgear change. There was no significant difference in repeated scores within machines with or without headgear change. For clinical purposes, care should be exercised when comparing nasalance scores between the old Nasometer and the Nasometer II.


Effect of the presence of brain-derived neurotrophic factor val(66)met polymorphism on the recovery in patients with acute subcortical stroke.
To investigate the effect of brain-derived neurotrophic factor (BDNF) Val(66)Met polymorphism on the recovery after subcortical stroke, using the modified Rankin Scale (mRS). Subcortical stroke patients with copies of BDNF Val(66)Met polymorphism (n=7) were compared to their controls (n=7) without a copy of BDNF Val(66)Met polymorphism after matching for initial severity, location and type of stroke. The mRS scores at 1 and 3 months after discharge from the neurorehabilitation unit were compared between the groups. A repeated measures ANOVA for mRS revealed significant interaction between time and group (F(2, 24) =37.2, p<0.001) and a significant effect of time (F(2, 24)=10.8, p<0.001), thereby reflecting significant differences between the Met allele (+) group and the Met allele (-) group. There was a significant difference in mRS scores at 3 months post-discharge between the two groups (p=0.01) although no difference was evident in mRS scores at 1 month post-discharge between the two groups. There were significant improvements between mRS scores on admission and mRS scores at 1 month post-discharge (p=0.02), and between mRS scores at 1 month post-discharge and mRS scores at 3 months post-discharge (p=0.004) in the Met allele (-) group. BDNF Val(66)Met polymorphism may be associated with worse functional outcome in Korean patients with subcortical stroke. Therefore, BDNF Val(66)Met polymorphism should be considered as an important prognostic factor for recovery and responses to rehabilitation therapies after stroke in Korean patients. There is a need for developing different rehabilitation strategies for the population with BDNF Val(66)Met polymorphism. Further studies assessing different outcomes for various functional domains of stroke recovery are needed to clarify the role of BDNF Val(66)Met polymorphism.


Association Between the 10-Year ASCVD Risk Score and COVID-19 Complications Among Healthy Adults (Analysis from the National Cohort COVID Collaborative).
COVID-19 complications have been linked to worse outcomes among patients with established atherosclerotic cardiovascular disease (ASCVD). Less is known about the cumulative consequences of multiple ASCVD risk factors on COVID-19 outcomes. We evaluated the dose-response associations between 10-year ASCVD risk scores and COVID-19 complications. The National COVID-19 Cohort Collaborative collects electronic health record data from over 70 US health systems. Our analysis was limited to patients with positive COVID-19 tests without documented ASCVD events at the time of the first positive test. We evaluated the dose-response associations between 10-year ASCVD risk scores, categorized into categorized as low (<7.5%), intermediate (7.5% to 20.0%), or high (>20.0%), and COVID-19 complications, including hospitalizations and mortality. We reported the outcomes using multivariable-adjusted hazard ratios and 95% confidence intervals (CIs). Our cohort included 120,335 patients with documented positive COVID-19 test results who were free of ASCVD events. The mean age was 51.9 ± 16.1 years, 59.4% were women, 15.3% were Black, and 13.7% were Hispanic/Latino. Overall, 15,363 patients (12.8%) were hospitalized and 2,058 (1.7%) died. Patients at intermediate risk of developing ASCVD were had a 1.49 (95% CI 1.41 to 1.56) increased risk of hospitalization and 1.77 (95% CI 1.76 to 1.79) increased risk of mortality compared with patients at low risk. Patients at high risk had a 2.23 (95% CI 2.10 to 2.38) increased risk of hospitalization and a 5.98 (95% CI 5.93 to 6.03) increased risk of mortality. In conclusion, patients in this nationwide cohort at high risk of developing ASCVD are at substantially greater risk of COVID-19 complications. COVID-19 mitigation efforts should focus on these patient populations.


A Synthetic Circuit for Mercury Bioremediation Using Self-Assembling Functional Amyloids.
Synthetic biology approaches to bioremediation are a key sustainable strategy to leverage the self-replicating and programmable aspects of biology for environmental stewardship. The increasing spread of anthropogenic mercury pollution into our habitats and food chains is a pressing concern. Here, we explore the use of programmed bacterial biofilms to aid in the sequestration of mercury. We demonstrate that by integrating a mercury-responsive promoter and an operon encoding a mercury-absorbing self-assembling extracellular protein nanofiber, we can engineer bacteria that can detect and sequester toxic Hg2+ ions from the environment. This work paves the way for the development of on-demand biofilm living materials that can operate autonomously as heavy-metal absorbents.


Favorable outcome with allogeneic hematopoietic stem cell transplantation in pediatric acquired aplastic anemia patients.
The data of allogeneic HSCT in nine children with acquired AA between June 1998 and July 2006 were analyzed retrospectively. The median duration of time to neutrophil and platelet engraftment was 18 and 25 days, respectively. None of the patients had primary graft failure. Two (22.2%) patients developed acute GVHD and of these, one (11.1%) was Grade 1, and the other (11.1%) was Grade 3. Although the study group was composed of higher risk patients, including six of nine resistant to previous immunosuppressive treatment, eight had multiple not irradiated or filtered transfusion histories and one of the cases was only 5/6 HLA-compatible with his donor, the five-yr overall and EFS was 100%, and all recipients are alive without any graft failure. This may be attributed to the dose adjusted use of ATG according to individual transfusion history and gradual tapering of CsA and cessation at least nine months after allogeneic HSCT.


Biocompatibility of BioAggregate and mineral trioxide aggregate on the liver and kidney.
To investigate and compare the systemic toxic effect of DiaRoot BioAggregate and grey ProRoot Mineral trioxide aggregate (MTA) on the liver and kidney after 7 and 30 days. Forty-two white albino rats were divided into two main groups. Group (1), considered the control group (n = 18), was further divided into two subgroups. The negative control subgroup (n = 6) received no treatment. The empty tube subgroup (n = 12) received empty sterile Teflon tubes. In Group (2), considered the experimental group (n = 24), the rats were divided equally into two subgroups. One subgroup received MTA, whilst the other received BioAggregate. The materials in the Teflon tubes were implanted subcutaneously in the dorsal side of the rats. Blood samples were taken to investigate the change of kidney and liver functions on day 7 and day 30. The liver and kidney organs were subjected to histopathological examination and calculation of the number of inflammatory cells. Data analysis was performed using one-way anova with post hoc multiple comparisons with the Tukey's test. Student's t-test was used to compare the changes in liver and kidney functions amongst the groups. On day 7, a significantly more severe inflammatory reaction was observed in both experimental subgroups compared with the control (P < 0.05); the severity decreased after 30 days. The kidney functions were not affected after 7 days but had subsequently increased after 30 days (P < 0.001). Liver functions increased after 7 days and had decreased in the BioAggregate subgroup after 30 days, whilst in the MTA subgroup, a continuous increase in the level of liver function was observed. Mineral trioxide aggregate had adverse effects on the liver and kidney that were significantly more severe than BioAggregate but with no permanent damage.


Assessment of mental health trajectories before and after myocardial infarction, atrial fibrillation or stroke: analysis of a cohort study in Tromsø, Norway (Tromsø Study, 1994-2016).
The increased survival rate of cardiovascular disease (CVD) implies a higher proportion of individuals who live with CVD. Using data from the Tromsø Study, we aimed to investigate mental health symptom trajectories before and after myocardial infarction, atrial fibrillation or stroke in a general population and to explore factors that contribute to the association. Cohort study. Sample drawn from inhabitants of the municipality of Tromsø, Norway, who participated in the Tromsø Study (1994-2016). A total of 18 719 participants (52.3% women) were included, and of these 2098 (32.9% women) were diagnosed with myocardial infarction, 1896 (41.9% women) with atrial fibrillation and 1263 (42.9% women) with stroke. Mental health symptoms were assessed using the Hopkins Symptom Checklist-10 and the Conor Mental Health Index. The participants who were diagnosed with either myocardial infarction or stroke had a significant monotonous increase in mental health symptoms before myocardial infarction (p=0.029) and stroke (p=0.029) that intensified at the time of diagnosis. After the event, the study found a higher prevalence of mental health symptoms with a decline in symptom levels over time for myocardial infarction (p<0.001) and stroke (p=0.004), but not for atrial fibrillation (before: p=0.180, after: p=0.410). The risk of elevated mental health symptoms with myocardial infarction, atrial fibrillation and stroke was associated with sex (p<0.001), age (p<0.01), physical activity (p<0.001), diabetes (p<0.05) and other comorbidities (p<0.001). The study indicates that mental health problems among individuals with myocardial infarction, atrial fibrillation and stroke may have started to develop several years before the cardiovascular event and suggests that successful CVD rehabilitation may need to consider previous life factors. Future research is recommended to examine whether health promotion measures in a general population also create mental health resilience after a CVD event.


The influences of skin visco-elasticity, hydration level and aging on the formation of wrinkles: a comprehensive and objective approach.
Various skin parameters including skin visco-elasticity and hydration level affect the formation of wrinkles. The aim of this study was to investigate the comprehensive and objective relationship between age, skin visco-elasticity, hydration level, and the occurrence of wrinkles using bioengineering equipments for the first time. A total number of 97 healthy women were included in this study. Age, Fitzpatrick skin type, skin mechanical parameters obtained with Cutometer(R0~R9), hydration level measured with Corneometer, as well as wrinkle parameters (SEsm, SEr, SEsc, and SEw) assessed with Visioscan, were analyzed with the Pearson's correlation test. The skin fluidity (R6) increased while the elastic recovery ratio (R7) decreased with the age. The wrinkle parameter (SEw) also increased with the age. The higher skin hysteresis values (R4 and R9) coincided with the higher SEw values. Skin hydration significantly lowered the hysteresis (R9), the wrinkles (SEw), and the depth of wrinkle furrows (R3mr). The elderly have less elastic skin and more wrinkles. Skin hysteresis most closely related with the degree of wrinkles. Drier skin showed more wrinkles and deeper furrows, with wider intervals. On the basis of these objective findings, we propose several skin parameters associated with wrinkles, and hypothesize the mechanism of wrinkle generation.


Mass gathering medical care: to calculate the Medical Usage Rate of Galway Races.
Medical Usage Rate (MUR) of Galway Races: The Galway Races is the most popular horse-racing festival in Ireland. It takes place for a week starting from the last Monday in July. The races are held at Ballybrit race course in Galway. During the 7 days of racing, about 180,000 people attend. The average temperature in Galway around that time of the year is around 15-200C. The aim of this study is to calculate the MUR of Galway Races and to develop a model to predict the MUR for Galway Races in future. The MUR of Galway Races is calculated by looking retrospectively at the medical records of the last 11 years of Galway Races from 1997 to 2007. The Galway Races has a MUR of 3.67 patient per ten thousand. Based on the figures for last 10 years, the predictive MUR for Galway Races 2008 calculated before the races and actual figures in 2008 races is comparable.


Hereditary hemochromatosis: presentation and diagnosis in the 1990s.
In the past, patients with hereditary hemochromatosis have been identified predominantly from symptomatic presentation or from family studies. In the 1990s, iron studies on routine screening chemistry panels have become more commonplace. The purpose of this paper is to describe the clinical, laboratory, and presenting features of a series of patients with hereditary hemochromatosis, diagnosed from 1990 to 1995. Clinical information, serum and liver iron studies, liver histology, and phlebotomy requirements were evaluated in 40 patients with newly diagnosed hereditary hemochromatosis prospectively referred to a tertiary university-based hepatology clinic. Eighty-three percent of patients came to medical attention as a result of screening blood work: 73% were asymptomatic and 78% had normal physical examinations. Only three patients had cirrhosis from hemochromatosis alone, only two were diabetic, and only two had increased skin pigmentation. These findings are in contrast to previous reports of hemochromatosis probands in which patients with symptoms and more advanced disease were identified. The hepatic iron concentration, hepatic iron index, and age at diagnosis were similar for men and women. With the use of screening iron studies on routine serum chemistry panels, patients with hemochromatosis can be identified and subsequently treated before they have symptoms or organ damage.


Light-promoted rhodopsin expression and starvation survival in the marine dinoflagellate Oxyrrhis marina.
The discovery of microbial rhodopsins in marine proteobacteria changed the dogma that photosynthesis is the only pathway to use the solar energy for biological utilization in the marine environment. Although homologs of these rhodopsins have been identified in dinoflagellates, the diversity of the encoding genes and their physiological roles remain unexplored. As an initial step toward addressing the gap, we conducted high-throughput transcriptome sequencing on Oxyrrhis marina to retrieve rhodopsin transcripts, rapid amplification of cDNA ends to isolate full-length cDNAs of dominant representatives, and quantitative reverse-transcription PCR to investigate their expression under varying conditions. Our phylogenetic analyses showed that O. marina contained both the proton-pumping type (PR) and sensory type (SR) rhodopsins, and the transcriptome data showed that the PR type dominated over the SR type. We compared rhodopsin gene expression for cultures kept under light: dark cycle and continuous darkness in a time course of 24 days without feeding. Although both types of rhodopsin were expressed under the two conditions, the expression levels of PR were much higher than SR, consistent with the transcriptomic data. Furthermore, relative to cultures kept in the dark, rhodopsin expression levels and cell survival rate were both higher in cultures grown in the light. This is the first report of light-dependent promotion of starvation survival and concomitant promotion of PR expression in a eukaryote. While direct evidence needs to come from functional test on rhodopsins in vitro or gene knockout/knockdown experiments, our results suggest that the proton-pumping rhodopsin might be responsible for the light-enhanced survival of O. marina, as previously demonstrated in bacteria.


Symptoms and signs of prostatism as risk factors for prostatectomy.
Symptom questionnaires and physical examinations administered periodically to 1,057 men followed prospectively for up to 30 years in the Baltimore Longitudinal Study of Aging (BLSA) were analyzed to determine which symptoms of prostatism were predictive of subsequent prostatectomy for benign prostatic hyperplasia (BPH). Change in the size and force of the urinary stream (P = 0.0001) and a sensation of incomplete emptying (P = 0.0005) were the only symptoms positively predictive in a multivariate analysis. Prostate enlargement by rectal palpation was an independent risk factor for prostatectomy (P less than 0.03) and was associated with hesitancy (P less than 0.02) and a sensation of incomplete emptying (P less than 0.02). Of the men with all three risk factors, 37% (41/112) eventually had a prostatectomy, in contrast to 8% of the remaining 945 men. This is the first study to document the extent to which urologic symptoms and a digital rectal examination predict subsequent prostatectomy for BPH.


Variability in Capillary Perfusion Is Increased in Regions of Retinal Ischemia Due to Branch Retinal Vein Occlusion.
To investigate alterations in macular perfusion variability due to branch retinal vein occlusion (BRVO) using a novel approach based on optical coherence tomography angiography (OCTA) coefficient of variation (CoV) analysis. Thirteen eyes of 13 patients with macular ischemia due to BRVO were studied. Multiple consecutive en face OCTA images were acquired. Bias field correction, spatial alignment, and normalization of intensities across the images were performed followed by pixelwise computation of standard deviation divided by the mean to generate a CoV map. Region of interest-based CoV values, derived from this map, for arterioles, venules, and the microvasculature were compared between regions with macular ischemia and control areas of the same eye. Control areas were regions of the same macula that were not affected by the BRVO and had normal retinal vascular structure as seen on multimodal imaging and normal retinal vascular density measurements as quantified using OCTA. CoV increased by a mean value of 17.6% within the microvasculature of ischemic regions compared to the control microvasculature (P < 0.0001). CoV measurements of microvasculature were consistently greater in the ischemic area of all 13 eyes compared to control. There were no differences in CoV measurements between ischemic and control areas for arterioles (P = 0.13) and venules (P = 1.0). Greater variability in microvasculature perfusion occurs at sites of macular ischemia due to BRVO. We report a novel way for quantifying macular perfusion variability using OCTA. This technique may have applicability for studying the pathophysiology of other retinal vascular diseases.


[Orbital pulse analyses in healthy subjects and patients with cerebral arteriosclerosis].
81 normotensive persons were examined with the ophthalmodyamographic method. The measuring device was fixed with a constant, hypodiastolic pressure, and orbital volume pulses were registered and analysed according to qualitative and quantitative pulse criteria. Pulse criteria of younger persons were compared to those of older patients, pulses of persons with a normal vascular system were compared to pulses of persons suffering from cerebral vascular sclerosis. The most important results can be summarized as follows: 1. In old age pulses with arciform ascent or deep-seated anacrotic inflection are found more often. 2. The applanation of the dicrotic wave is seen more often in older patients and most often in patients with cerebral arteriosclerosis. Yet it is not specific for regressive changes of the arterial wall. 3. Pulses of the peripheral type with decrement of the incisura are found more often in younger persons with unimpaired blood vessels, presumably because of the more viscous-plastic properties of the vascular wall. 4. The quotient of dicrotism increases in old age. 5. The mean value of pulse wave transmission time, as a rule, diminishes in older persons, but non-hypertensive patients with cerebral arteriosclerosis have an increased pulse wave transmission time when compared to persons of the same age group without vascular changes. 6. Concerning the diagnostic value of differences between left and right it is important to notice that physiological differences of pulse criteria are considerable as far as amplitudes and height of discrotism are concerned; they are less prominent as to the period of rapid ejection (time between beginning of steep ascent and primary peak) and practivally below the measurable range as to semi-amplitude time (time that passes until half of the maximum amplitude is reached) and pulse wave transmission time. That means: measurable differences in regard to semi-amplitude time or pulse wave transmission time are reliable diagnostic criteria whereas differences in amplitudes and height of discrotism may bring false positive results.


GAN-based metal artifacts region inpainting in brain MRI imaging with reflective registration.
Metallic magnetic resonance imaging (MRI) implants can introduce magnetic field distortions, resulting in image distortion, such as bulk shifts and signal-loss artifacts. Metal Artifacts Region Inpainting Network (MARINet), using the symmetry of brain MRI images, has been developed to generate normal MRI images in the image domain and improve image quality. T1-weighted MRI images containing or located near the teeth of 100 patients were collected. A total of 9000 slices were obtained after data augmentation. Then, MARINet based on U-Net with a dual-path encoder was employed to inpaint the artifacts in MRI images. The input of MARINet contains the original image and the flipped registered image, with partial convolution used concurrently. Subsequently, we compared PConv with partial convolution, and GConv with gated convolution, SDEdit using a diffusion model for inpainting the artifact region of MRI images. The mean absolute error (MAE) and peak signal-to-noise ratio (PSNR) for the mask were used to compare the results of these methods. In addition, the artifact masks of clinical MRI images were inpainted by physicians. MARINet could directly and effectively inpaint the incomplete MRI images generated by masks in the image domain. For the test results of PConv, GConv, SDEdit, and MARINet, the masked MAEs were 0.1938, 0.1904, 0.1876, and 0.1834, respectively, and the masked PSNRs were 17.39, 17.40, 17.49, and 17.60 dB, respectively. The visualization results also suggest that the network can recover the tissue texture, alveolar shape, and tooth contour. Additionally, for clinical artifact MRI images, MARINet completed the artifact region inpainting task more effectively when compared with other models. By leveraging the quasi-symmetry of brain MRI images, MARINet can directly and effectively inpaint the metal artifacts in MRI images in the image domain, restoring the tooth contour and detail, thereby enhancing the image quality.


"It's not as easy as saying, 'just get them to eat more veggies'": Exploring healthy eating in residential care in Australia.
Young people living in residential out-of-home care (henceforth OoHC) are at increased risk of becoming overweight or obese. Currently, recognition of the everyday mechanisms that might be contributing to excess weight for children and young people in this setting is limited. The aim of this study was to better understand the barriers and complexities involved in the provision of a 'healthy' food environment in residential OoHC. Heightening awareness of these factors and how they might compromise a young person's physical health, will inform the development, refinement and evaluation of more sensitive and tailored weight-related interventions for this population. The paper presents a nuanced picture of the complexity of everyday food routines in residential care, and illustrates the ways in which food is 'done' in care; how food can be both symbolic of care but also used to exercise control; the way in which food can be used to create a 'family-like' environment; and the impact of traumatic experiences in childhood on subsequent behaviours and overall functioning in relation to food. It is argued that a health agenda designed for a mainstream population ignores the very complex relationship that children in residential OoHC may have with food. It is recommended that future intervention approaches account for personal food biographies, trauma and children's social backgrounds and how these are implicated in everyday practices and interactions around food.


Surgical treatment of lumbar ossification of the posterior longitudinal ligament. Report of two cases and description of surgical technique.
The authors report two cases of patients with lumbar ossification of the posterior longitudinal ligament (OPLL). One patient underwent surgery via the single posterior approach, and the other patient underwent combined anterior-posterior surgery. The authors consider the anterior approach for excision of the ossified lesion to be the most reasonable for treatment of lumbar OPLL. It is extremely important, however, to select the surgical procedure according to the individual patient's condition.


A galactosyl(alpha 1-3)mannose epitope on phospholipids of Leishmania mexicana and L. braziliensis is recognized by trypanosomatid-infected human sera.
An immunoglobulin M antibody reactive with galactosyl(alpha 1-3)mannose [Gal(alpha 1-3)Man] residues present on phospholipids extracted from Leishmania mexicana and L. braziliensis was found to be present in high titer in the serum of every normal individual studied. Periodate oxidation, acid hydrolysis, or acetylation suppressed immunoreactivity, suggesting that an oligosaccharide chain was responsible for antibody binding. Interaction occurs only with alpha-Gal terminal residues, since treatment of purified glycophospholipids with alpha-galactosidase but not with beta-galactosidase abolished it. Antibody bound to galactosyl(alpha 1-3)galactose-linked synthetic antigens but did not bind to the same residues present in rabbit, rat, and guinea pig erythrocytes or in murine laminin. Antigen-antibody binding was strongly blocked with Gal(alpha 1-3)Man and Gal(beta 1-4)Man. These results plus inhibition studies with several oligosaccharides suggest that they are indeed different from antibodies against the galactosyl(alpha 1-3)galactose residue. Anti-Gal(alpha 1-3)Man antibody values were significantly elevated in 89% of patients with diffuse cutaneous leishmaniasis, 84% of patients with localized cutaneous leishmaniasis, 69% of patients with mucocutaneous leishmaniasis, and 44 and 62% of patients with Trypanosoma cruzi or T. rangeli infection, respectively, but not in patients with 15 other different infectious and inflammatory diseases. Anti-Gal(alpha 1-3)Man antibody readily absorbed to American Leishmania and Trypanosoma culture forms, suggesting a surface membrane localization of reactive epitope. Gal(alpha 1-3)Man-bearing glycophospholipid was easily extracted from American Leishmania promastigotes and T. cruzi trypomastigotes as well as from American Trypanosoma culture forms. The possibility that this antibody arises against parasitic glycophospholipid-linked Gal(alpha 1-3)Man terminal residues is proposed.


Variation in end-of-life decision making between critical care consultants.
Considerable variation in end-of-life decision making is reported between intensive care units in the United Kingdom, possibly because of differences in casemix. Senior medical staff within any one unit should, however, be consistent in such decision making. We reviewed the medical records for a 4-year period to establish if there was consistency in our own unit. This revealed considerable variation in the apparent willingness of consultants to make end-of-life decisions, emphasising the subjective nature of these decisions. Personality typing (Myers-Briggs Type Indicator) of consultants revealed that those who had made more than the expected number of decisions had scores towards the judging end of the judging/perceiving domain.


Test for interactions between a genetic marker set and environment in generalized linear models.
We consider in this paper testing for interactions between a genetic marker set and an environmental variable. A common practice in studying gene-environment (GE) interactions is to analyze one single-nucleotide polymorphism (SNP) at a time. It is of significant interest to analyze SNPs in a biologically defined set simultaneously, e.g. gene or pathway. In this paper, we first show that if the main effects of multiple SNPs in a set are associated with a disease/trait, the classical single SNP-GE interaction analysis can be biased. We derive the asymptotic bias and study the conditions under which the classical single SNP-GE interaction analysis is unbiased. We further show that, the simple minimum p-value-based SNP-set GE analysis, can be biased and have an inflated Type 1 error rate. To overcome these difficulties, we propose a computationally efficient and powerful gene-environment set association test (GESAT) in generalized linear models. Our method tests for SNP-set by environment interactions using a variance component test, and estimates the main SNP effects under the null hypothesis using ridge regression. We evaluate the performance of GESAT using simulation studies, and apply GESAT to data from the Harvard lung cancer genetic study to investigate GE interactions between the SNPs in the 15q24-25.1 region and smoking on lung cancer risk.


Specific antibody-receptor interactions trigger InlAB-independent uptake of Listeria monocytogenes into tumor cell lines.
Specific cell targeting is an important, yet unsolved problem in bacteria-based therapeutic applications, like tumor or gene therapy. Here, we describe the construction of a novel, internalin A and B (InlAB)-deficient Listeria monocytogenes strain (Lm-spa+), which expresses protein A of Staphylococcus aureus (SPA) and anchors SPA in the correct orientation on the bacterial cell surface. This listerial strain efficiently binds antibodies allowing specific interaction of the bacterium with the target recognized by the antibody. Binding of Trastuzumab (Herceptin®) or Cetuximab (Erbitux®) to Lm-spa+, two clinically approved monoclonal antibodies directed against HER2/neu and EGFR/HER1, respectively, triggers InlAB-independent internalization into non-phagocytic cancer cell lines overexpressing the respective receptors. Internalization, subsequent escape into the host cell cytosol and intracellular replication of these bacteria are as efficient as of the corresponding InlAB-positive, SPA-negative parental strain. This specific antibody/receptor-mediated internalization of Lm-spa+ is shown in the murine 4T1 tumor cell line, the isogenic 4T1-HER2 cell line as well as the human cancer cell lines SK-BR-3 and SK-OV-3. Importantly, this targeting approach is applicable in a xenograft mouse tumor model after crosslinking the antibody to SPA on the listerial cell surface. Binding of receptor-specific antibodies to SPA-expressing L. monocytogenes may represent a promising approach to target L. monocytogenes to host cells expressing specific receptors triggering internalization.


Outcomes of repeat transcatheter aortic valve replacement with balloon-expandable valves: a registry study.
With increasing numbers of patients undergoing transcatheter aortic valve replacement (TAVR), data on management of failed TAVR, including repeat TAVR procedure, are needed. The aim of this study was to assess the safety and efficacy of redo-TAVR in a national registry. This study included all consecutive patients in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry from Nov 9, 2011, to Dec 30, 2022 who underwent TAVR with balloon-expandable valves in failed transcatheter heart valves (redo-TAVR) or native aortic valves (native-TAVR). Procedural, echocardiographic, and clinical outcomes were compared between redo-TAVR and native-TAVR cohorts using propensity score matching. Among 350 591 patients (1320 redo-TAVR; 349 271 native-TAVR), 1320 propensity-matched pairs of patients undergoing redo-TAVR and native-TAVR were analysed (redo-TAVR cohort: mean age 78 years [SD 9]; 559 [42·3%] of 1320 female, 761 [57·7%] male; mean predicted surgical risk of 30-day mortality 8·1%). The rates of procedural complications of redo-TAVR were low (coronary compression or obstruction: four [0·3%] of 1320; intraprocedural death: eight [0·6%] of 1320; conversion to open heart surgery: six [0·5%] of 1319) and similar to native-TAVR. There was no significant difference between redo-TAVR and native-TAVR populations in death at 30 days (4·7% vs 4·0%, p=0·36) or 1 year (17·5% vs 19·0%, p=0·57), and stroke at 30 days (2·0% vs 1·9%, p=0·84) or 1 year (3·2% vs 3·5%, p=0·80). Redo-TAVR reduced aortic valve gradients at 1 year, although they were higher in the redo-TAVR group compared with the native-TAVR group (15 mm Hg vs 12 mm Hg; p<0·0001). Moderate or severe aortic regurgitation rates were similar between redo-TAVR and native-TAVR groups at 1 year (1·8% vs 3·3%, p=0·18). Death or stroke after redo-TAVR were not significantly affected by the timing of redo-TAVR (before or after 1 year of index TAVR), or by index transcatheter valve type (balloon-expandable or non-balloon-expandable). Redo-TAVR with balloon-expandable valves effectively treated dysfunction of the index TAVR procedure with low procedural complication rates, and death and stroke rates similar to those in patients with a similar clinical profile and predicted risk undergoing TAVR for native aortic valve stenosis. Redo-TAVR with balloon-expandable valves might be a reasonable treatment for failed TAVR in selected patients. Edwards Lifesciences.


Nutra-ergonomics: influence of nutrition on physical employment standards and the health of workers.
The importance of ergonomics across several scientific domains, including biomechanics, psychology, sociology, and physiology, have been extensively explored. However, the role of other factors that may influence the health and productivity of workers, such as nutrition, is generally overlooked. Nutra-ergonomics describes the interface between workers, their work environment, and performance in relation to their nutritional status. It considers nutrition to be an integral part of a safe and productive workplace that encompasses physical and mental health as well as the long-term wellbeing of workers. This review explores the knowledge, awareness, and common practices of nutrition, hydration, stimulants, and fortified product use employed prior to physical employment standards testing and within the workplace. The influence of these nutra-ergonomic strategies on physical employment standards, worker safety, and performance will be examined. Further, the roles, responsibilities, and implications for the applicant, worker, and the employer will be discussed within the context of nutra-ergonomics, with reference to the provision and sustainability of an environment conducive to optimize worker health and wellbeing. Beyond physical employment standards, workplace productivity, and performance, the influence of extended or chronic desynchronization (irregular or shift work) in the work schedule on metabolism and long-term health, including risk of developing chronic and complex diseases, is discussed. Finally, practical nutra-ergonomic strategies and recommendations for the applicant, worker, and employer alike will be provided to enhance the short- and long-term safety, performance, health, and wellbeing of workers.


The E2 "gene" of bovine papillomavirus encodes an enhancer-binding protein.
The E2 early open reading frame (presumably gene) of bovine papillomavirus-1 was fused in frame with the collagen-beta-galactosidase-encoding region of the vector pJG200 and was expressed in and partially purified from Escherichia coli. The hybrid protein specifically bound to the enhancer region of bovine papillomavirus at several sites. DNase I-cleavage protection analysis of one such site revealed the protected sequence. A comparison of the protected sequence with the remainder of the DNA sequences that also have affinity for the protein revealed a consensus sequence having the motif AATTGGCGGNNCG, in which N is any nucleotide. The protected region also includes a sequence with 2-fold rotational symmetry--ATCGGTG/CACCGAT.


Ca2+ as a mediator of ischemic preconditioning.
We tested the hypothesis that elevation of [Ca2+]i during ischemic preconditioning (IPC) stimulates protein kinase C (PKC), which confers the protection against the ischemic injury. Langendorff-perfused rat hearts were subjected to 40-minute global ischemia followed by 30-minute reperfusion (I/R). In preconditioned groups, hearts were subjected to either IPC, consisting of 5-minute global ischemia and 10-minute reperfusion, or high-Ca2+ preconditioning (HCPC), ie, the 5-minute perfusion of higher Ca2+ perfusate (2.3 mmol/L Ca2+) followed by 10-minute perfusion of normal perfusate (1.8 mmol/L Ca2+), and then were subjected to I/R. A significant functional recovery and decreased lactate dehydrogenase release were observed in HCPC and IPC hearts compared with ischemic control hearts. ATP contents of preconditioned hearts were significantly higher than those of the ischemic control hearts. The cell structure in preconditioned hearts was preserved better than that in the ischemic control hearts. Furthermore, the activation and translocation of PKC from cytoplasm to sarcolemma were observed in the preconditioned hearts. Verapamil administered during IPC significantly attenuated the salutary effects of IPC. Administration of chelerythrine, a specific PKC inhibitor, completely abolished the HCPC- and IPC-induced cardioprotection. The translocation of PKC by IPC was blocked by verapamil or chelerythrine. Immunohistochemical study using rabbit polyclonal antibody against PKC isoforms indicated that stress induced by IPC or HCPC evoked the translocation of PKC alpha and PKC delta to the cell membrane. Translocation of PKC isoforms was attenuated by the treatment with verapamil or chelerythrine. These results demonstrate that (1) a transient increase in [Ca2+]i during IPC is an important trigger for the activation of PKC, which is responsible for cardioprotection; (2) the elevation of [Ca2+]i during IPC, at least partly, resulted from Ca2+ entry via voltage-dependent Ca2+ channel; and (3) activation and translocation of PKC alpha and PKC delta occur during IPC and HCPC and may be important in preconditioning.


Molecular mechanisms involved in development of cerebral vasospasm.
Although the agents responsible for production of vasospasm have not yet been clearly identified, the author reviews the molecular mechanisms involved in development of vasospasm mainly based on the experimental data in a canine two-hemorrhage model. The blood products after subarachnoid hemorrhage most likely stimulate many cell membrane receptors, such as G protein-coupled receptors and receptor tyrosine kinases, to activate the tyrosine kinase pathway of the vascular smooth muscle cells. The activation of the tyrosine kinase pathway is associated with continuous elevation of intracellular Ca++ levels and activation of mu-calpain; the former may result mainly not from Ca++ release but from Ca++ influx from outside the cells. The increased intracellular Ca++ concentrations stimulate Ca++/calmodulin (CaM)-dependent myosin light chain kinase to phosphorylate myosin light chain continuously during vasospasm. A topical application of genistein, ethylene-glycol-bis(Beta-aminoethylether) N,N'-tetraacetic acid, or various L-type Ca++ channel blockers likely induces reversal of vasospasm as a result of a decrease in intracellular Ca++ levels. The blood products also activate the rho/rho-associated kinase pathway during vasospasm most likely via G protein-coupled receptors, and the activated rho-associated kinase inhibits myosin phosphatase through phosphorylation at its myosin-binding subunit to induce Ca++-independent development of vasospasm. The enhanced generation of arachidonic acid during vasospasm may also contribute to inhibition of myosin phosphatase, at least in part, through the rho/rho-associated kinase pathway. The activity of myosin phosphatase in vasospam can also be inhibited by activated protein kinase C independently of the rho/rho-associated kinase pathway, but the inhibition may play a minor and transient role in contractile regulation. The protein levels of thin filament-associated proteins, calponin and caldesmon, are progressively decreased in vasospasm, whereas their phosphorylation levels are increased. Both changes probably contribute to the enhancement of smooth muscle contractility. Contractile and cytoskeletal proteins appear to be degraded in vasospasm by proteolysis with activated mu-calpain, suggesting that the intracellular devices responsible for smooth-muscle contraction are severely degraded in vasospasm. It remains to be determined the extent to which Ca++-dependent and -independent contractile regulations, proteolysis and phosphorylation of thin filament-associated proteins, and degradation of contractile and cytoskeletal proteins are involved in the development of vasospasm.