Synthesis and diabetic neuropathic pain-alleviating effects of 2N-(pyrazol-3-yl)methylbenzo[d]isothiazole-1,1-dioxide derivatives.
A novel series of fused-benzensulfonamide 2-N-(pyrazol-3-yl)methylbenzo[d]isothiazole-1,1-dioxide derivatives was designed and synthesized as metabolically stable T-type calcium channel inhibitors. Several compounds, 9, 10, and 17, displayed potent T-type channel inhibitory activity. Among them, compounds 10 and 17 showed good metabolic stability in human liver microsomes, and low hERG channel and CYP450 inhibition. Compound 10 exhibited diabetic neuropathic pain-alleviating effects in a streptozotocin-induced peripheral diabetic neuropathy (PDN) model. The maximum efficacy of compound 10, which was 3-fold more potent than gabapentin, was observed at 1h after administration, and co-administration of compound 10 with gabapentin showed a considerable synergic effect.


Identification of low frequency patterns in backpropagation neural networks.
Although neural networks have been widely applied to medical problems in recent years, their applicability has been limited for a variety of reasons. One of these barriers has been the inability to discriminate rare classes of solutions (i.e., the identification of categories that are infrequent). In this article, I demonstrate that a system of hierarchical neural networks (HNN) can overcome the problem of recognizing low frequency patterns, and therefore can improve the prediction power of neural-network systems. HNN are designed according to a divide-and-conquer approach: Triage networks are able to discriminate supersets that contain the infrequent pattern, and these supersets are then used by Specialized networks, which discriminate the infrequent pattern from the other ones in the superset. The supersets that are discriminated by the Triage networks are based on pattern similarity. The application of multilayered neural networks in more than one step allows the prior probability of a given pattern to increase at each step, provided that the predictive power of the network at the previous level is high. The method has been applied to one artificial set and one real set of data. In the artificial set, the distribution of the patterns was known and no noise was present. In this experiment, the HNN provided better discrimination than a standard neural network for all classes. In a real data set of nine thousand patients who were suspected of having thyroid disorders, the HNN also provided higher sensitivity than its corresponding standard neural network (without a corresponding decay in specificity) given the same time constraints.(ABSTRACT TRUNCATED AT 250 WORDS)


Visual compatibility of colistin injection with other antibiotics during simulated Y-site administration.
The compatibility of colistin with other antibiotics at concentrations commonly used in intensive care units was studied. A vial of colistin was dissolved in sterile water for injection. The reconstituted solution (colistin base 75 mg/mL) was then diluted in 0.9% sodium chloride injection in polyvinyl chloride (PVC) infusion bag to give a total volume of 100 mL (colistin 1.5 mg/mL). Secondary drugs, including cefoperazone-sulbactam, ceftazidime, ertapenem, fosfomycin, imipenem-cilastatin, linezolid, meropenem, piperacillin-tazobactam, and vancomycin, were reconstituted if necessary and then diluted in 0.9% sodium chloride injection in PVC infusion bags to give final study concentrations of one-hundredth of their initial concentrations. The admixtures were collected in beakers at the end of the i.v. line and stored at 26 °C under constant fluorescent light throughout the study. Compatibility was assessed visually during delivery of each drug pair at time 0 and at 1 hour after starting the infusion. Compatibility was defined as the absence of visually detected particulate formation, haze, precipitation, color change, or gas evolution. Each combination was tested in triplicate. No particulate formation or other evidence of incompatibility was found in any of the studied drug combinations when observed immediately after mixing or at 1 hour. No particulate matter was observed with the unaided eyes, during microscopic evaluation, or against black and white backgrounds. Colistin 1.5 mg/mL was visually compatible with single concentrations of 9 other antimicrobial products during simulated Y-site injection at 26 °C without light protection for at least 1 hour.


Surveillance of Severe Acute Respiratory Infection (SARI) for Hospitalized Patients in Northern Vietnam, 2011-2014.
Severe acute respiratory infections (SARI) are leading causes of hospitalization, morbidity, and mortality in children worldwide. The aim of this study was to identify viral pathogens responsible for SARI in northern Vietnam in the period from 2011 to 2014. Throat swabs and tracheal aspirates were collected from SARI patients according to WHO guidelines. The presence of 13 different viral pathogens (influenza A[H1N1]pdm09; A/H3N2; A/H5; A/H7 and B; para influenza 1,2,3; RSV; HMPV; adeno; severe acute respiratory syndrome-CoV and rhino) was tested by conventional/real-time reverse transcription-polymerase chain reaction. During the study period, 975 samples were collected and tested. More than 30% (32.1%, 313 samples) of the samples showed evidence of infection with influenza viruses, including A/H3N2 (48 samples), A (H1N1) pdm09 (221 samples), influenza B (42 samples), and co-infection of A (H1N1) pdm09 or A/H3N2 and influenza B (2 samples). Other respiratory pathogens were detected in 101 samples, including rhinovirus (73 samples), adenovirus (10 samples), hMPV (9 samples), parainfluenza 3 (5 samples), parainfluenza 2 (3 samples), and RSV (1 sample). Influenza A/H5, A/H7, or SARS-CoV were not detected. Respiratory viral infection, particularly infection of influenza and rhinoviruses, were associated with high rates of SARI hospitalization, and future studies correlating the clinical aspects are needed to design interventions, including targeted vaccination.


Predicting Engagement in Electronic Surveillance in Romantic Relationships.
The Internet is a common medium through which people engage in interpersonal electronic surveillance (IES) of one another. We know little empirically about what predicts IES in romantic relationships. The present study expands on factors identified in previous studies (including demographic characteristics, relational characteristics, and other psychosocial variables) to predict surveillance in romantic relationships. Internet users in established romantic relationships (n = 259) completed inventories on the frequency of surveillance behavior, relationship variables, demographic variables, and Internet usage variables. Hierarchical regression was applied to understand relationships between these behaviors and surveillance. The regression supported that relationship variables and Internet use variables significantly predicted IES in romantic relationships. These findings further our understanding of the Internet to surveil partners.


Involvement of NK1+ CD4- CD8- alphabeta T cells and endogenous IL-4 in non-MHC-restricted rejection of embryonal carcinoma in genetically resistant mice.
Non-MHC-restricted rejection mechanisms against the murine MHC-negative F9 embryonal carcinoma cells were analyzed. Strains of C57BL/6 (B6) background were resistant to the tumors irrespective of H-2 haplotypes, while others, including BALB/c background, were susceptible. This resistance was suggested to be mediated primarily by the host thymus-dependent alphabeta T cells, since both athymic B6 nude and normal B6 mice depleted with alphabeta T cells showed susceptible phenotype. The difference of the nature of alphabeta T cells infiltrating in H-2-identical B6- and BALB.B-derived tumors was then comparatively analyzed. It was revealed that unique T cells with NK1+ CD4- CD8- (double negative (DN)) alphabeta TCR+ phenotype were accumulated significantly in B6, but few in BALB.B mice. The population freshly isolated from the F9 tumor tissues preferentially expressed potent IL-4 mRNA, and was suggested to be mostly responsible for the endogenous IL-4 production. Indeed, the injection of either anti-NK1.1 or anti-IL-4-neutralizing Ab into the normal B6 rendered them significantly susceptible to the tumor cells. These results strongly suggested that NK1+ DN alphabeta T cells were responsible primarily for the rejection mechanisms against F9 tumors. Histologically, F9 tumors in B6 mice were characterized by abundant macrophage infiltration and massive tumor necrosis, neither of which was observed in those in BALB.B nor B6 mice preinjected with anti-IL-4 Ab, indicating that both histologic features in the resistant strain were dependent on the endogenous IL-4. Present results provide one of the first instances in which a recently emerging minor T cell subpopulation, thymus-dependent NK1+ DN alphabeta T cells, plays an essential role in anti-tumor responses in vivo.


Medicare's next voyage: encouraging physicians to adopt health information technology.
Although there is growing consensus that health information technology (HIT) will be critical to improving health care quality and reducing costs, physicians' investments in technology remain limited. As the largest single U.S. purchaser of health care services, Medicare has the power to promote physician adoption of HIT. The Centers for Medicare and Medicaid Services should clarify its technology objectives, engage the physician community, shape the development of standards and technology certification criteria, and adopt concrete payment systems to promote adoption of meaningful technology that furthers the interests of Medicare beneficiaries.


A new marker of coronary collateral flow in patients presenting with acute myocardial infarction.
Multimerin-2 is an adhesion substrate between pericytes and basal membranes during angiogenesis. The present study aimed to assess the relationship between serum Multimerin-2 and coronary collateral flow grade. Between April 2022 and August 2022, 88 patients with subacute ST-elevation myocardial infarction were included in this study. The main inclusion criteria were patients who present 12-48 hours after symptom onset and aged between 18 and 90 years. The patients were divided into two groups according to the Rentrop classification: poor collateral group (Rentrop grade 0-1) and good collateral group (Rentrop grade 2-3). Biochemical and hematological parameters were measured before coronary angiography. Serum Multimerin-2 levels were found to be significantly different between the two groups, and levels were higher in the Rentrop 2-3 group than in the Rentrop 0-1 group (3,527.9 ± 1,194.2 pg/ml and 946.7 ± 249.1 pg/ml; p < 0.00). Receiver operating characteristic curve analysis indicated that the area under the curve was 0.918 (p = 0.001), and the best cut-off value of 849 pg/ml had a sensitivity of 90.1% and a specificity of 84.1% for predicting Rentrop grade 2-3 coronary flow. The number of patients with low left ventricular ejection fraction (LVEF) by echocardiography at 30 days was significantly higher in patients with poor collateralization. Multimerin-2 levels were found to be higher in patients with Rentrop grade 2-3 coronary flow than Rentrop grade 0-1 coronary flow after myocardial infarction. We detected a potential relationship between MMR-2 and good coronary collateral formation.


MRI Features in a Rat Model of H-ABC Tubulinopathy.
Tubulinopathies are a group of recently described diseases characterized by mutations in the tubulin genes. Mutations in TUBB4A produce diseases such as dystonia type 4 (DYT4) and hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC), which are clinically diagnosed by magnetic resonance imaging (MRI). We propose the taiep rat as the first animal model for tubulinopathies. The spontaneous mutant suffers from a syndrome related to a central leukodystrophy and characterized by tremor, ataxia, immobility, epilepsy, and paralysis. The pathological signs presented by these rats and the morphological changes we found by our longitudinal MRI study are similar to those of patients with mutations in TUBB4A. The diffuse atrophy we found in brain, cerebellum and spinal cord is related to the changes detectable in many human tubulinopathies and in particular in H-ABC patients, where myelin degeneration at the level of putamen and cerebellum is a clinical trademark of the disease. We performed Tubb4a exon analysis to corroborate the genetic defect and formulated hypotheses about the effect of amino acid 302 change on protein physiology. Optical microscopy of taiep rat cerebella and spinal cord confirmed the optical density loss in white matter associated with myelin loss, despite the persistence of neural fibers.


Metal-organic framework (MOF)-incorporated polymeric electrolyte realizing fast lithium-ion transportation with high Li+ transference number for solid-state batteries.
Composite polymer electrolytes (CPEs) show significant advantages in developing solid-state batteries due to their high flexibility and easy processability. In CPEs, solid fillers play a considerable effect on electrochemical performances. Recently, metal-organic frameworks (MOFs) are emerging as new solid fillers and show great promise to regulate ion migration. Herein, by using a Co-based MOF, a high-performance CPE is initially prepared and studied. Benefiting from the sufficient interactions and pore confinement from MOF, the obtained CPE shows both high ionic conductivity and a high Li+ transference number (0.41). The MOF-incorporated CPE then enables a uniform Li deposition and stable interfacial condition. Accordingly, the as-assembled solid batteries demonstrate a high reversible capacity and good cycling performance. This work verifies the practicability of MOFs as solid fillers to produce advanced CPEs, presenting their promising prospect for practical application.


Space proton flux and the temporal distribution of cardiovascular deaths.
The influence of solar activity (SA) and geomagnetic activity (GMA) on human homeostasis has long been investigated. The aim of the present study was to analyse the relationship between monthly proton flux (> 90 MeV) and other SA and GMA parameters and between proton flux and temporal (monthly) distribution of total and cardiovascular-related deaths. The data from 180 months (1974-1989) of distribution in the Beilinson Campus of the Rabin Medical Centre, Israel, and of 108 months (1983-1991) from the Kaunas Medical Academy, were analysed and compared with SA, GMA and space proton flux (> 90 MeV). It was concluded: (1) monthly levels of SA, GMA and radiowave propagation (Fof2) are significantly and adversely correlated with monthly space proton flux (> 90 MeV); (2) medical-biological phenomena that increase during periods of low solar and/or geomagnetic activity may be stimulated by physical processes provoked by the concomitant increase in proton flux; (3) the monthly number of deaths related (positively or negatively) to SA are significantly and adversely related to the space proton flux (> 90 MeV).


Growth phase- and nutrient limitation-associated transcript abundance regulation in Bordetella pertussis.
To survive in a host environment, microbial pathogens must sense local conditions, including nutrient availability, and adjust their growth state and virulence functions accordingly. No comprehensive investigation of growth phase-related gene regulation in Bordetella pertussis has been reported previously. We characterized changes in genome-wide transcript abundance of B. pertussis as a function of growth phase and availability of glutamate, a key nutrient for this organism. Using a Bordetella DNA microarray, we discovered significant changes in transcript abundance for 861 array elements during the transition from log phase to stationary phase, including declining transcript levels of many virulence factor genes. The responses to glutamate depletion exhibited similarities to the responses induced by exit from log phase, including decreased virulence factor transcript levels. However, only 23% of array elements that showed at least a fourfold growth phase-associated difference in transcript abundance also exhibited glutamate depletion-associated changes, suggesting that nutrient limitation may be one of several interacting factors affecting gene regulation during stationary phase. Transcript abundance patterns of a Bvg+ phase-locked mutant revealed that the BvgAS two-component regulatory system is a key determinant of growth phase- and nutrient limitation-related transcriptional control. Several adhesin genes exhibited lower transcript abundance during stationary phase and under glutamate restriction conditions. The predicted bacterial phenotype was confirmed: adherence to bronchoepithelial cells decreased 3.3- and 4.4-fold at stationary phase and with glutamate deprivation, respectively. Growth phase and nutrient availability may serve as cues by which B. pertussis regulates virulence according to the stage of infection or the location within the human airway.


Prevalence and awareness of Anabolic Androgenic Steroids (AAS) among gymnasts in the western province of Riyadh, Saudi Arabia.
Anabolic Androgenic Steroids (AAS) are synthetic derivatives of the male sex hormone (testosterone) that are increasingly used by athletes as performance enhancing drugs to increase muscle mass and strength. Multiple health adverse effects may be caused by its non-medical use. Several international and regional studies showed the high prevalence of AAS usage and low level of awareness of it among different populations. To estimate the prevalence of AAS and to determine the level of awareness toward it among gymnasts in the western province of Riyadh. This cross-sectional survey was conducted using a self-administered questionnaire distributed on 400 male gymnasts from 10 different fitness centers which have been chosen randomly from 23 centers in the western province of Riyadh city (Kingdom of Saudi Arabia) during 2016. Data analysis was performed by SPSS version 21, using descriptive statistics and Chi-square test. Among the 400 gymnasts who participated in the survey, a total of n=363 questionnaires were received completed. Of the responders, (n=89) were AAS users with a percentage 24.50%. The testosterone was the most commonly used type followed by Methandrostenolone then Stanozolol. The major sources for obtaining AAS were online shopping (45%) and gym-coach (22.5%). Regarding awareness, 74% of AAS users had an inadequate perception about AAS concept versus 55% of non-users with no significant difference (p=0.076). In addition, 82% of AAS users and 83% of non-users had inadequate knowledge of AAS adverse effects with no significant difference between the two categories (p=0.087). The usage of AAS is high amongst gymnasts in the western province of Riyadh city considering they are prohibited. The level of awareness toward AAS is low among most gymnasts. We recommend for educational programs to be established in order to increase public awareness, in addition to a tightening of control by the responsible authorities over the sources of AAS procurement.


Effectiveness of preventive dentistry delivery system.
A preventive dentistry delivery system was developed for maximum effectiveness in private practice. Four new pit or fissure carious lesions developed in 20 patients who were 10 to 20 years old at the start of a two-year exploratory test; there were no new lesions of smooth surfaces. Of the incipient lesions that were under observation, no increase was observed in 23 of 26 pit or fissure lesions, 24 to 25 proximal and all of 26 buccal or lingual smooth surface lesions. In 33 patients 21 to 30 years old at the start of the test, no new lesions appeared and growth of the 142 incipient lesions appeared to be arrested. A low level of gingivitis was maintained in all patients who were tested.


A cell-based ribozyme reporter system employing a chromosomally-integrated 5' exonuclease gene.
Bioinformatic genome surveys indicate that self-cleaving ribonucleic acids (ribozymes) appear to be widespread among all domains of life, although the functions of only a small number have been validated by biochemical methods. Alternatively, cell-based reporter gene assays can be used to validate ribozyme function. However, reporter activity can be confounded by phenomena unrelated to ribozyme-mediated cleavage of RNA. We established a ribozyme reporter system in Escherichia coli in which a significant reduction of reporter activity is manifest when an active ribozyme sequence is fused to the reporter gene and the expression of a foreign Bacillus subtilis RNaseJ1 5' exonuclease is induced from a chromosomally-integrated gene in the same cell. The reporter system could be useful for validating ribozyme function in candidate sequences identified from bioinformatics.


Inactivation of tumor suppressor genes and the progression of adult T-cell leukemia-lymphoma.
Almost three decades have passed since adult T-cell leukemia-lymphoma (ATLL) was proposed as a new disease entity. During this period, its causative agent, human T-cell leukemia virus type-1 (HTLV-1), was found and a crucial role of the viral product Tax in the development of ATLL was disclosed. However, the long latent period after infection with HTLV-1 indicates the need for additional factors for full-blown ATLL, most of which are supposed to be provided by somatic mutations of cellular genes. Recent progress in cell-cycle research has revealed that the uncontrolled and superior proliferative activity of malignant cells is mainly caused by the breakdown of cell-cycle regulation and that most malignancies carry aberrations in p16-pRB and/or p53 pathways. ATLL is not an exception, despite the consistent association of HTLV-1 in primary leukemia cells, and accumulating evidence indicates that the breakdown of these pathways is indeed involved in the leukemogenesis of ATLL, especially in its later steps, which serve as the key events for promotion of indolent ATLL to aggressive ATLL.


Serum D-dimer level as a predictor of neurological functional prognosis in cases of head injuries caused by road traffic accidents.
The number of traffic fatalities is declining in Japan; however, a large proportion of head injuries are still attributable to traffic accidents. Severe head trauma may cause progressive and devastating coagulopathy owing to exacerbated coagulation and fibrinolysis, which results in massive bleeding and poor patient outcomes. D-dimer is a fibrinolytic marker, which remarkably increases in severe coagulopathy due to the exacerbated fibrinolytic system. Because the degree of coagulopathy is associated with patient outcomes, the D-dimer level is a useful prognostic predictor in patients with head trauma. However, the usefulness of D-dimer in cases of head trauma caused by road traffic accidents remains inadequately explored. In this study, we investigated the relationship between D-dimer levels and outcomes in head injuries caused by traffic accidents. We extracted data on traffic injuries from Japan Neuro-Trauma Data Bank Project 2015, which is a prospective multicenter registry of head injuries. The analysis included 335 individuals with no missing data. The outcome variable was the score of the Glasgow Outcome Scale (GOS), a neurological outcome index. The participants were categorized into the favorable outcome (GOS score ≥ 4) and poor outcome (GOS score ≤ 3) groups. The serum D-dimer levels at the time of admission were divided into four categories at the quartiles, and the reference category was less than the first quartile (< 17.4 µg/mL). We performed a logistic regression analysis with GOS as the dependent variable and D-dimer as a predictor and performed a multivariate analysis that was adjusted for 10 physiological parameters. In the univariate analysis, all groups with serum D-dimer values ≥ 17.4 μg/dL showed significantly poorer outcomes than those of the reference group. In the multivariate analysis, after adjusting for other factors, D-dimer levels ≥ 89.3 μg/dL were an independent predictor of poor outcome. After adjusting for physiological parameters, high serum D-dimer levels can be an independent factor for predicting neurological prognosis in head trauma caused by road traffic accidents.


Geometrical criteria for formation of coiled-coil structures of polypeptide chains.
Crick's general formulas describing a coiled coil are expressed in a different form to combine the parameters of a coiled coil with the backbone dihedral angles of a polypeptide chain, assuming that the bond lengths and bond angles of the chain are fixed. While the existence of a low-energy coiled-coil conformation depends on energetic considerations, these formulas, which pertain to single-stranded structures and, by application of symmetry operations, to multistranded structures, provide the geometrical criteria for the existence of coiled coils. The concept of "the averaged structure of the minor helix", introduced here, makes it possible to relate the shape of the major helix to that of the minor helix. It is shown, in the analysis of a simple model of a single-stranded coiled-coil beta structure, that strong geometrical restrictions exist for the formation of coiled-coil structures from a given minor helix conformation of a polypeptide chain; these restrictions are expressed in a general form that is applicable to any coiled-coil of any number of residues in a repeat unit. As an application, the possible existence of a two-stranded coiled-coil antiparallel beta structure is considered, both geometrically and energetically, and discussed in relation to the observed twisted beta structures in globular proteins. The proposed coiled-coil models of alpha-helical proteins are also examined briefly.


Tuberculous peritonitis in a child undergoing continuous ambulatory peritoneal dialysis.
We present a 13-year-old girl with Arnold-Chiari syndrome and uremia secondary to neurogenic bladder. She had been treated with continuous ambulatory peritoneal dialysis (CAPD) for 13 months prior to the development of peritonitis. The patient demonstrated no improvement with a 3-day therapy of intraperitoneal vancomycin and netilmicin. Meanwhile, smear of centrifuged dialysate revealed acid fast bacilli on two occasions. We, then, started anti-TB therapy with oral isoniazid (INAH), rifampin and ethambutal. The symptoms subsided within three days. In the first week, the patient lost her peritoneal ultrafiltration and needed daytime automatic peritoneal dialysis. At the last follow-up examination, 12 months after treatment, she remained well on standard CAPD.


FID sampling superior to spin-echo sampling for T2*-based quantification of holmium-loaded microspheres: theory and experiment.
This work demonstrates both theoretically and experimentally that multiple gradient-echo sampling of free induction decay (MGEFID) is superior to MGE sampling of spin echo (MGESE) for T2*-based quantification of holmium-loaded microspheres (HoMS). An interleaved sampling strategy was applied in great detail to characterize the MR signal behavior of FID and SE signals of gels and perfused rabbit livers containing HoMS in great detail. Diffusion sensitivity was demonstrated for MGESE sampling, resulting in non-exponential signal decay on both sides of the SE peak and in an underestimation of the HoMS concentration. Other than MGESE sampling, MGEFID sampling was demonstrated to be insensitive to diffusion, to exhibit exponential signal decay, and to allow accurate T2*-based quantification of HoMS. Furthermore, a fit procedure was proposed extending the upper limit of quantifiable R2* relaxation rates to at least 1500 sec(-1). With this post-processing step incorporated, MGEFID was shown to correctly estimate the integral amount of inhomogeneously distributed HoMS in liver tissue, up to a clinically relevant limit. All experimental findings could be explained with the theory of nuclear magnetic resonance (NMR) signal behavior in magnetically inhomogeneous tissues. HoMS were shown to satisfy the static dephasing regime when investigated with MGEFID and to violate the static dephasing conditions for MGESE at longer echo times typically used in SE.


The significance of HER-2/neu/c-erbB-2 gene amplification in benign and malignant breast disease.
This study was carried out to investigate the amplification of HER-2/neu oncogene in 66 patients with primary breast cancer and 90 samples from benign breast disease (BBD). The amplification of HER-2/neu oncogene in the DNA of paraffin-embedded specimens was determined by differential PCR. Nineteen out of 66 (28.8%) breast cancer patients showed amplification of the gene. No gene amplification was found in benign breast disease. There was no significant correlation of HER-2/neu amplification with, age, menopausal status, the number of positive nodes, tumor size, estrogen receptor, however, amplification of HER-2/neu gene was strongly correlated with nodal status (p = 0.0049). In node positive patients, the incidence of HER-2/neu amplification was high (43%). These findings indicate that the amplification of HER-2/neu gene may be of pathogenetic significance in breast cancer and may have a poor prognosis in node positive breast cancer patients while no gene amplification in benign breast disease suggests that HER-2/neu amplification is a late molecular alteration event in the pathogenesis of breast cancer.


68Ga-PSMA PET/CT for the detection of bone metastasis in recurrent prostate cancer and a PSA level <2 ng/ml: Two case reports and a literature review.
Localization of prostate cancer recurrence, particularly in the bones, is a major challenge with standard of care imaging in patients with biochemical recurrence following curatively intended treatment. Gallium-68-labeled prostate specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA PET/CT) is a novel and promising method for imaging in prostate cancer. The present study reports two cases of patients with prostate cancer with biochemical recurrence, with evidence of bone metastases on 68Ga-PSMA PET/CT images and low prostate specific antigen PSA levels (<2 ng/ml) and PSA doubling time >6 months. The bone metastases were verified by supplementary imaging with 18F-sodium fluoride PET/CT and magnetic resonance imaging as well as biochemical responses to androgen deprivation therapy. Therefore, 68Ga-PSMA PET/CT is promising for the restaging of patients with prostate cancer with biochemical recurrence, including patients with low PSA levels and low PSA kinetics.


A Case Report of Paraneoplastic Pemphigus Associated With Retroperitoneal Inflammatory Myofibroblastic Tumor.
Paraneoplastic pemphigus (PNP) is an autoimmune bullous disease associated with underlying neoplasms, both malignant and benign. The most constant clinical presentation of PNP is the presence of intractable stomatitis. Herein we present a 25-year-old male with a 3-month history of refractory stomatitis especially involving the lips and widespread vesiculobullous eruption on his trunk and extremities. The diagnosis of PNP was confirmed based on histological and serological results. Investigation for the underlying neoplasm revealed a retroperitoneal tumorous mass which was biopsied and diagnosed as the inflammatory myofibroblastic tumor (IMT). The tumor was surgically excised, and different treatment regimens were used to treat the mucocutaneous lesions. Skin lesions responded favorably to treatment, but oral stomatitis still persists which is the case in most PNP patients. This combination of PNP and IMT has rarely been reported in the literature. Treatment started with corticosteroid and rituximab then tumor excised.


Adaptation of the Tinnitus Handicap Inventory into Polish and its testing on a clinical population of tinnitus sufferers.
To describe how the Tinnitus Handicap Inventory (THI) was translated into Polish (THI-POL) and to present psychometric data on how well it performed in a clinical population of tinnitus sufferers. The original version of THI was adapted into Polish. The reliability of THI-POL was investigated using test-retest, Cronbach's alpha, endorsement rate and item-total correlation. Construct validity and convergent validity were also assessed based on confirmatory factor analysis, inter-item correlation and Pearson product-moment correlations using subscale A (Tinnitus) of the Tinnitus and Hearing Survey (THS-POL); divergent validity was checked using subscale B (Hearing) of THS-POL. A group of 167 adults filled in THI-POL twice over their three-day hospitalisation period. Test-retest reliability for the total THI-POL scores was strong (r = 0.91). Cronbach's alpha coefficient for the total score was high (r = 0.95), confirming the questionnaire's stability. Confirmatory factor analysis (CFA) and inter-item correlation did not confirm the three-factor model. Convergent validity from the Tinnitus subscale of THS showed a positive strong (r = 0.75) correlation. Divergent validity showed only a moderate correlation. All analyses were statistically significant (p < 0.01). THI-POL is a valid and reliable self-administered tool, which allows the overall tinnitus handicap of Polish-speaking patients to be effectively assessed.


Keeping an eye on pink eye: a global conjunctivitis outbreak expert survey.
Recurrent conjunctivitis epidemics are prevalent worldwide. Aetiologies are often undetermined. We surveyed conjunctivitis researchers about perceived trends in prevalence, incidence and aetiologies of conjunctivitis epidemics. Of the 155 participants, 7% endorsed globally variable and dynamic microbial aetiologies of conjunctivitis epidemics. Increased incidence of conjunctivitis epidemics over the last decade were reported by 21% of respondents. Peak seasons differed between the northern and southern hemispheres. There is regional equipoise regarding the increasing incidence and emerging underlying aetiologies of epidemic conjunctivitis. Further investigation of global surveillance and microbial characterization of conjunctivitis outbreaks could improve prevention and outcomes.


Outcome probability modulates anticipatory behavior to signals that are equally reliable.
A stimulus is a reliable signal of an outcome when the probability that the outcome occurs in its presence is different from in its absence. Reliable signals of important outcomes are responsible for triggering critical anticipatory or preparatory behavior, which is any form of behavior that prepares the organism to receive a biologically significant event. Previous research has shown that humans and other animals prepare more for outcomes that occur in the presence of highly reliable (i.e., highly contingent) signals, that is, those for which that difference is larger. However, it seems reasonable to expect that, all other things being equal, the probability with which the outcome follows the signal should also affect preparatory behavior. In the present experiment with humans, we used two signals. They were differentially followed by the outcome, but they were equally (and relatively weakly) reliable. The dependent variable was preparatory behavior in a Martians video game. Participants prepared more for the outcome (a Martians' invasion) when the outcome was most probable. These results indicate that the probability of the outcome can bias preparatory behavior to occur with different intensities despite identical outcome signaling.


Multi-modal tissue sampling in cone beam CT guided navigation bronchoscopy: comparative accuracy of different sampling tools and rapid on-site evaluation of cytopathology.
Advanced technological aids are frequently used to improve outcome of transbronchial diagnostics for peripheral pulmonary lesions. Even when lesion access has been confirmed by 3D imaging, obtaining an accurate tissue sample however remains difficult. In this single institution study, we evaluate the comparative accuracy of different sampling methodologies and the accuracy of rapid on-site evaluation of cytopathology (ROSE) in navigation bronchoscopy cases where imaging has confirmed the catheter to have accurately accessed the lesion. All consecutive navigation bronchoscopies in between December 2017- June 2020 performed in a room with a cone beam CT (CBCT) system where catheter position was intra-procedurally confirmed to be within or adjacent to the lesion by cone beam CT and augmented fluoroscopy were included. Individual tool outcomes were compared against one another and follow-up outcome. A mean of 11.39 samples using 2.93 tools were obtained in 225 lesions (median diameter 15 mm, 195 patients). A correct diagnosis was most often obtained by forceps (accuracy 70.6%), followed by 1.1 mm cryoprobe (68.4%), needle aspiration (46.7%), 1.9 mm cryoprobe (41.2%), brush (30.3%) and lavage (23.7%). Procedural outcome corresponded to follow-up outcome in 75.1% of lesions (80.5% of patients). Accurately diagnosed lesions were sampled significantly more often (11.91 vs. 9.72 samples, P=0.014). In cases where procedural outcome proved malignant, ROSE had also detected this in 47.5%. Of all clinically available biopsy tools, the forceps showed most often accurate. However, extensive multi-modal sampling resulted in highest diagnostic accuracy. A hypothetical multi-modal approach of only using forceps and needle aspiration provided eventual diagnostic outcome in 91.7% of successfully diagnosed lesions. In the circumstances of our study, confirmation of malignancy on ROSE did not reduce number of biopsies taken nor biopsy time. Future research on how to improve the accuracy and effectivity of tissue sampling is needed.


Cross-linker-mediated regulation of actin network organization controls tissue morphogenesis.
Contraction of cortical actomyosin networks driven by myosin activation controls cell shape changes and tissue morphogenesis during animal development. In vitro studies suggest that contractility also depends on the geometrical organization of actin filaments. Here we analyze the function of actomyosin network topology in vivo using optogenetic stimulation of myosin-II in Drosophila embryos. We show that early during cellularization, hexagonally arrayed actomyosin fibers are resilient to myosin-II activation. Actomyosin fibers then acquire a ring-like conformation and become contractile and sensitive to myosin-II. This transition is controlled by Bottleneck, a Drosophila unique protein expressed for only a short time during early cellularization, which we show regulates actin bundling. In addition, it requires two opposing actin cross-linkers, Filamin and Fimbrin. Filamin acts synergistically with Bottleneck to facilitate hexagonal patterning, while Fimbrin controls remodeling of the hexagonal network into contractile rings. Thus, actin cross-linking regulates the spatio-temporal organization of actomyosin contraction in vivo, which is critical for tissue morphogenesis.


Three-dimensional Si/Ge quantum dot crystals.
Modern nanotechnology offers routes to create new artificial materials, widening the functionality of devices in physics, chemistry, and biology. Templated self-organization has been recognized as a possible route to achieve exact positioning of quantum dots to create quantum dot arrays, molecules, and crystals. Here we employ extreme ultraviolet interference lithography (EUV-IL) at a wavelength of lambda = 13.5 nm for fast, large-area exposure of templates with perfect periodicity. Si(001) substrates have been patterned with two-dimensional hole arrays using EUV-IL and reactive ion etching. On these substrates, three-dimensionally ordered SiGe quantum dot crystals with the so far smallest quantum dot sizes and periods both in lateral and vertical directions have been grown by molecular beam epitaxy. X-ray diffractometry from a sample volume corresponding to about 3.6 x 10(7) dots and atomic force microscopy (AFM) reveal an up to now unmatched structural perfection of the quantum dot crystal and a narrow quantum dot size distribution. Intense interband photoluminescence has been observed up to room temperature, indicating a low defect density in the three-dimensional (3D) SiGe quantum dot crystals. Using the Ge concentration and dot shapes determined by X-ray and AFM measurements as input parameters for 3D band structure calculations, an excellent quantitative agreement between measured and calculated PL energies is obtained. The calculations show that the band structure of the 3D ordered quantum dot crystal is significantly modified by the artificial periodicity. A calculation of the variation of the eigenenergies based on the statistical variation in the dot dimensions as determined experimentally (+/-10% in linear dimensions) shows that the calculated electronic coupling between neighboring dots is not destroyed due to the quantum dot size variations. Thus, not only from a structural point of view but also with respect to the band structure, the 3D ordered quantum dots can be regarded as artificial crystal.


PARASITE LOAD, BODY SIZE, AND AGE OF WILD-CAUGHT MALE FIELD CRICKETS (ORTHOPTERA: GRYLLIDAE): EFFECTS ON SEXUAL SELECTION.
Comparison of male field crickets (Gryllus veletis and G. pennsylvanicus) collected either by themselves (solitary) or with one or more females (paired) showed that the paired males were significantly older and significantly less parasitized by gregarines (protozoan gut parasites) than were solitary males. Body size did not differ between the two groups. These results corroborate earlier experimental findings that females are preferentially attracted to older males and suggest that the ability of less parasitized males to produce more spermatophores under laboratory conditions may also be important in the field. Calculation of sexual-selection differentials and gradients for G. pennsylvanicus did not reveal any indirect selection on body size and confirmed the strong selection on male age.


E-cigarette, or vaping, product use-associated lung injury (EVALI) treated with veno-venous extracorporeal membrane oxygenation (VV-ECMO) and ultra-protective ventilator settings.
A 19-year-old man vaping with tetrahydrocannabinol presented with dyspnoea and right pneumothorax. History, imaging and negative infectious workup were consistent with E-cigarette, or vaping, product use-associated lung injury (EVALI). Treated with systemic steroids, he developed acute respiratory distress syndrome and was intubated requiring veno-venous extracorporeal membrane oxygenation (VV-ECMO) by hospital day 3. Using VV-ECMO, very-low tidal volume ventilation of 1.5 cc/kg was achieved, as was daily ambulation. VV-ECMO was decannulated on hospital day 9 and the patient was extubated the next day. He was discharged home on hospital day 13 without oxygen. At post-intensive care unit clinic follow-up, he had lost 20 kg of weight while hospitalised and reported nightmares. Patients with EVALI may be supported with VV-ECMO, which allows ultra-lung-protective mechanical ventilation that may minimise ventilator-induced lung injury. Follow-up in patients with EVALI is essential to diagnose and treat comorbidities, follow lung function and prevent relapses.


FGF, Mechanism of Action, Role in Parkinson's Disease, and Therapeutics.
Parkinson's disease (PD) is a neurodegenerative disease associated with severe disability and adverse effects on life quality. In PD, motor dysfunction can occur, such as quiescence, muscle stiffness, and postural instability. PD is also associated with autonomic nervous dysfunction, sleep disorders, psychiatric symptoms, and other non-motor symptoms. Degeneration of dopaminergic neurons in the substantia nigra compact (SNPC), Lewy body, and neuroinflammation are the main pathological features of PD. The death or dysfunction of dopaminergic neurons in the dense part of the substantia nigra leads to dopamine deficiency in the basal ganglia and motor dysfunction. The formation of the Lewy body is associated with the misfolding of α-synuclein, which becomes insoluble and abnormally aggregated. Astrocytes and microglia mainly cause neuroinflammation, and the activation of a variety of pro-inflammatory transcription factors and regulatory proteins leads to the degeneration of dopaminergic neurons. At present, PD is mainly treated with drugs that increase dopamine concentration or directly stimulate dopamine receptors. Fibroblast growth factor (FGF) is a family of cellular signaling proteins strongly associated with neurodegenerative diseases such as PD. FGF and its receptor (FGFR) play an essential role in the development and maintenance of the nervous system as well as in neuroinflammation and have been shown to improve the survival rate of dopaminergic neurons. This paper summarized the mechanism of FGF and its receptors in the pathological process of PD and related signaling pathways, involving the development and protection of dopaminergic neurons in SNPC, α-synuclein aggregation, mitochondrial dysfunction, and neuroinflammation. It provides a reference for developing drugs to slow down or prevent the potential of PD.


Cost-effectiveness of treatments reducing coronary heart disease mortality in Ireland, 2000 to 2010.
Coronary heart disease (CHD) is associated with a large burden of disease in Ireland and is responsible for more than 6000 deaths annually. This study examined the cost-effectiveness of specific CHD treatments in Ireland. Irish epidemiological data on patient numbers and median survival in specific groups, plus the uptake, effectiveness, and costs of specific interventions, all stratified by age and sex, were incorporated into a previously validated CHD mortality model, the IMPACT model. This model calculates the number of life-years gained (LYGs) by specific cardiology interventions to generate incremental cost-effectiveness ratios (ICERs) per LYG for each intervention. In 2000, medical and surgical treatments together prevented or postponed approximately 1885 CHD deaths in patients aged 25 to 84 years, and thus generated approximately 14,505 extra life-years (minimum 7270, maximum 22,475). In general, all the cardiac interventions investigated were highly cost-effective in the Irish setting. Aspirin, beta-blockers, ACE inhibitors, spironolactone, and warfarin for specific conditions were the most cost-effective interventions (< euro 3000/LYG), followed by the statins for secondary prevention (< euro 6500/LYG). Revascularization for chronic angina and primary angioplasty for myocardial infarction, although still cost-effective, had the highest ICER (between euro 12,000 and euro 20,000/LYG). Using a comprehensive standardized methodology, cost-effectiveness ratios in this study clearly favored simple medical treatments for myocardial infarction, secondary prevention, angina, and heart failure.


Three-dimensional evaluation of the repeatability of scans of stone models and impressions using a blue LED scanner.
In this study, we evaluated the repeatability of scans of stone models and impressions of abutment teeth using a blue LED scanner and compared the findings between different abutment teeth types. For the stone models as well as impression of the canines, premolars, and molars, we generated 10 color-difference-maps and reports for each tooth type (n=10 per tooth type). One-way analysis of variance (ANOVA) and independent t-tests were performed to evaluate the repeatability of scans of the stone models and impressions obtained from a blue LED scanner. Our results indicate a high repeatability of scans of stone models and impressions of abutment teeth using the blue LED scanner and suggest a possible clinical advantage for scanning impressions of different abutment teeth types.


Experiences of Individuals With Visual Impairments in Integrated Physical Education: A Retrospective Study.
The purpose of this retrospective study was to examine the experiences of adults with visual impairments during school-based integrated physical education (PE). An interpretative phenomenological analysis (IPA) research approach was used and 16 adults (ages 21-48 years; 10 women, 6 men) with visual impairments acted as participants for this study. The primary sources of data were semistructured audiotaped telephone interviews and reflective field notes, which were recorded during and immediately following each interview. Thematic development was undertaken utilizing a 3-step analytical process guided by IPA. Based on the data analysis, 3 interrelated themes emerged from the participant transcripts: (a) feelings about "being put to the side," frustration and inadequacy; (b) "She is blind, she can't do it," debilitating feelings from physical educators' attitudes; and (c) "not self-esteem raising," feelings about peer interactions. The 1st theme described the participants' experiences and ascribed meaning to exclusionary practices. The 2nd theme described the participants' frustration over being treated differently by their PE teachers because of their visual impairments. Lastly, "not self-esteem raising," feelings about peer interactions demonstrated how participants felt about issues regarding challenging social situations with peers in PE. Utilizing an IPA approach, the researchers uncovered 3 interrelated themes that depicted central feelings, experiences, and reflections, which informed the meaning of the participants' PE experiences. The emerged themes provide unique insight into the embodied experiences of those with visual impairments in PE and fill a previous gap in the extant literature.


Construction of Chiral 1,3-Diamines through Rhodium-Catalyzed Asymmetric Arylation of Cyclic N-Sulfonyl Imines.
A rhodium/sulfur-olefin complex catalyzed asymmetric 1,2-addition of arylboronic acids to six-membered 1,2,6-thiadiazinane 1,1-dioxide-type cyclic imines to access highly optically active sulfamides (95-99% ee) has been developed. By taking advantage of the simple functional group transformations, an interesting array of valuable chiral 1,3-diamines with different substitution patterns can be readily obtained in a highly enantioenriched manner.


Size-temperature phase diagram for small Lennard-Jones clusters.
The size-temperature "phase diagram" for small Lennard-Jones clusters LJn (n< or =147) is constructed based on the analysis of the heat capacities Cv(T) , computed by the parallel tempering Monte Carlo method. Two types of "phase transitions" are often observed: the higher-temperature solid-liquid transition, due to melting of the cluster core, and the lower-temperature melting that occurs within the surface layer. The latter transition can only be observed for clusters with Mackay packing of the overlayer.


On the oxy analogues to the 4 leads to 1 intramolecularly hydrogen-bonded peptide conformations.
The occurrence of the oxy analogue to the type II' 4 leads to 1 intramolecularly hydrogen-bonded nonhelical peptide conformation, recently proposed for t-BOC-Gly-L-Pro-OH in the solid state by Deber on the basis of infrared absorption evidence, has been disproved by x-ray diffraction analysis. This type of folding is also absent in solvents of moderate or high polarity. The latter conclusion is in agreement with Deber's results. However, in solvents of low polarity this intramolecularly hydrogen-bonded form could account for the strong negative Cotton effect near 230 nm observed in the circular dichroism spectrum.


Emulated trial investigating effects of multiple treatments: estimating combined effects of mucoactive nebulisers in cystic fibrosis using registry data.
People with cystic fibrosis (CF) are often on multiple long-term treatments, including mucoactive nebulisers. In the UK, the most common mucoactive nebuliser is dornase alfa (DNase). A common therapeutic approach for people already on DNase is to add hypertonic saline (HS). The effects of DNase and HS used alone have been studied in randomised trials, but their effects in combination have not. This study investigates whether, for people already prescribed DNase, adding HS has additional benefit for lung function or use of intravenous antibiotics. Using UK CF Registry data from 2007 to 2018, we emulated a target trial. We included people aged 6 years and over who were prescribed DNase without HS for 2 years. We investigated the effects of combinations of DNase and HS over 5 years of follow-up. Inverse-probability-of-treatment weighting was used to control confounding. The period predated triple combination CF transmembrane conductance regulator modulators in routine care. 4498 individuals were included. At baseline, average age and forced expiratory volume in 1 s (FEV1%) predicted were 21.1 years and 69.7 respectively. During first year of follow-up, 3799 individuals were prescribed DNase alone; 426 added HS; 57 switched to HS alone and 216 were prescribed neither. We found no evidence that adding HS improved FEV1% at 1-5 years, or use of intravenous antibiotics at 1-4 years, compared with DNase alone. For individuals with CF prescribed DNase, we found no evidence that adding HS had an effect on FEV1% or prescription of intravenous antibiotics. Our study illustrates the emulated target trial approach using CF Registry data.


MHC class II loading of high or low affinity peptides directed by Ii/peptide fusion constructs: implications for T cell activation.
CD4(+) T cells recognize peptides presented on the cell surface of antigen presenting cells in the MHC class II context. The biosynthesis and transport of MHC class II molecules depend on the type II transmembrane invariant chain (Ii) and are tightly regulated processes. Ii is known to bind to the MHC class II peptide-binding groove via its class II-associated Ii peptide (CLIP) region early in the biosynthetic pathway to prevent premature peptide binding. In this study we have genetically exchanged CLIP with peptides of either high or low affinity for the class II peptide binding groove and utilized the properties of Ii to manipulate MHC class II loading. An inducible promoter controlled expression of the Ii/peptide fusion constructs, and presentation at different expression levels was studied. Both peptides were excised from Ii and presented on MHC class II molecules as shown by liquid chromatography-tandem mass spectrometry, but the high affinity peptide was presented more efficiently than the low affinity peptide. Both peptides were efficient in eliciting T cell responses at high Ii/peptide concentration independent of the duration of T cell stimulation. The peptides were also able to elicit an IL-2 response at low expression levels; however, the kinetic differed as the T cells required longer duration of T cell contact to reach a significant T cell response. This probably reflects the number of class II/peptide complexes at the cell surface and is discussed.


[Theophylline-induced changes in the presynaptic effects of adenosine, baclofen, clofelin and morphine in the myenteric plexus of the guinea pig].
The experiments on the isolated guinea-pig ileum have shown that the contractions caused by low frequency transmural stimulation are decreased by adenosine, baclofen, clofelin and morphine. Theophylline is a competing antagonist of adenosine and a noncompeting antagonist of baclofen, clofelin and morphine. The effects of the latter are not altered by 1,3-dipropyl-8-phenylxanthine suppressing adenosine effects. It is concluded that presynaptic effects of baclofen, clofelin and morphine depend on cAMP level in cholinergic neurons of myenteric plexus.


An update on modeling dose-response relationships: Accounting for correlated data structure and heterogeneous error variance in linear and nonlinear mixed models.
Advanced methods for dose-response assessments are used to estimate the minimum concentrations of a nutrient that maximizes a given outcome of interest, thereby determining nutritional requirements for optimal performance. Contrary to standard modeling assumptions, experimental data often present a design structure that includes correlations between observations (i.e., blocking, nesting, etc.) as well as heterogeneity of error variances; either can mislead inference if disregarded. Our objective is to demonstrate practical implementation of linear and nonlinear mixed models for dose-response relationships accounting for correlated data structure and heterogeneous error variances. To illustrate, we modeled data from a randomized complete block design study to evaluate the standardized ileal digestible (SID) Trp:Lys ratio dose-response on G:F of nursery pigs. A base linear mixed model was fitted to explore the functional form of G:F relative to Trp:Lys ratios and assess model assumptions. Next, we fitted 3 competing dose-response mixed models to G:F, namely a quadratic polynomial (QP) model, a broken-line linear (BLL) ascending model, and a broken-line quadratic (BLQ) ascending model, all of which included heteroskedastic specifications, as dictated by the base model. The GLIMMIX procedure of SAS (version 9.4) was used to fit the base and QP models and the NLMIXED procedure was used to fit the BLL and BLQ models. We further illustrated the use of a grid search of initial parameter values to facilitate convergence and parameter estimation in nonlinear mixed models. Fit between competing dose-response models was compared using a maximum likelihood-based Bayesian information criterion (BIC). The QP, BLL, and BLQ models fitted on G:F of nursery pigs yielded BIC values of 353.7, 343.4, and 345.2, respectively, thus indicating a better fit of the BLL model. The BLL breakpoint estimate of the SID Trp:Lys ratio was 16.5% (95% confidence interval [16.1, 17.0]). Problems with the estimation process rendered results from the BLQ model questionable. Importantly, accounting for heterogeneous variance enhanced inferential precision as the breadth of the confidence interval for the mean breakpoint decreased by approximately 44%. In summary, the article illustrates the use of linear and nonlinear mixed models for dose-response relationships accounting for heterogeneous residual variances, discusses important diagnostics and their implications for inference, and provides practical recommendations for computational troubleshooting.


A hybrid technique combining intramedullary pinning with extramedullary plate fixation in unstable and comminuted radial head fractures following on-table reconstruction.
Management of comminuted radial fractures remains controversial. Currently, the emergence of on-table reconstruction technique has made fixation in comminuted radial head fractures more viable. However, the present study reported an intro-operative unstable displacement from the reconstructed radial head to the neck during plate fixation, characterized by a poor radiocapitellar contact and incongruity between the radial head and neck. A hybrid technique combining with intramedullary pining was performed in our study to restore the normal alignment and maintain the stability of fixation. Therefore, the purpose of this article aimed to prove the feasibility of unstable comminuted radial head fractures treated with the extramedullary plate and intramedullary pinning fixation using titanium elastic nails. The clinical, functional and radiographic outcomes of the groups were compared during follow-up. The radiographic examination was conducted to evaluate the status of bone union, heterotopic ossification and post-traumatic arthritis. The functional assessment was performed to evaluate clinical effects, which included measurements of range of motion (ROM) in the elbow, Visual Analog Scale (VAS) score, Elbow Self-Assessment score (ESAS), Mayo Elbow Performance score (MEPS), and Disabilities of the Arm, Shoulder, and Hand (DASH)Outcome Measure score. Thirteen patients with unstable fractures were participated with an average follow-up of (38.6 ± 4.5) months for the experimental group and (32.0 ± 6.3) months for the control group, respectively. The functional outcomes in the experimental group, including MEPS and DASH, were significantly superior to the control group. However, no significant difference was observed in the elbow ROM and VAS score between two groups. In the last follow-up, one patient with post-traumatic arthritis rated as grades 1 and two with heterotopic ossifications were observed in the experimental group. In the control group, degenerative changes were observed in three cases (grade 1 in two cases and grade 2 in one case) and heterotopic ossifications rated as grade I were found in two patients. Collectively, intramedullary pinning with extramedullary plate fixation is feasible in unstable comminuted radial head fractures, which can be considered as a remedial surgery for on-table reconstruction technique.


Primary hyperaldosteronism diagnosed with adrenal vein sampling. Characteristics and follow-up after adrenalectomy in a Danish study.
Primary hyperaldosteronism (PA), known as Mb Conn, is one of the most common forms of secondary hypertension in middle-aged adults. High plasma aldosterone has been associated with severe organ damage. The unilateral aldosterone-producing adenoma (lateralized disease) is a subtype of PA, which can be fully or partly cured by adrenalectomy. Retrospective review of data from 50 patients who underwent adrenal venous sampling (AVS) was performed. Medical records, plasma renin and aldosteron, confirmatory tests and medical imaging (predominantly Computed Tomography and Magnetic Resonance Imaging) were available. Patients with lateralized disease (n = 39) underwent adrenalectomy and additional clinical data at least one year after surgery was recorded. Age and gender were widely and equally distributed (median age = 51, age span = 28-73). Patients with lateralized disease had higher blood pressure (BP) and lower serum potassium compared to patients with bilateral hyperplasia. No difference regarding age and gender distribution was detected. Despite lateralized disease diagnosed from AVS, the medical images were normal in 10 patients (28%). Follow-up of 30 patients who underwent adrenalectomy showed that six patients were cured, 17 had better BP control, five patients had no effect and one patient had higher BP but decreased number of antihypertensive drugs. PA is of equal prevalence in men and women, young and old individuals. The agreement between imaging modalities and AVS is limited, and the final diagnosis must rely on AVS. Patients prone for surgery had better BP control after adrenalectomy.


Surgical management of intercondylar fractures of the humerus using triceps reflecting anconeus pedicle (TRAP) approach.
Operative fixation of intra-articular fractures of the distal humerus requires adequate exposure. The transolecranon approach is a commonly used approach. The olecranon osteotomy has potential complications related to prominence/migration of hardware, displacement/nonunion of osteotomy and triceps weakness. Triceps-reflecting anconeus pedicle (TRAP) approach avoids the olecranon osteotomy without compromising the operative exposure. We present outcome of fixation of displaced intra-articular distal humeral fractures with the use of TRAP approach. We reviewed the functional and radiological results of 40 consecutive patients with intercondylar fractures of the humerus treated by internal fixation through TRAP approach. There were 28 males and 12 females and the average age was 32 ± 4.5 years. The right elbow was involved in 27 patients and the left elbow in 13 patients. The mechanism of injury was a fall in 20 patients, a motor-vehicle accident in 16 patients and direct trauma in four patients. At a minimum follow-up of 12 months (average 18 ± 4 months) 35 (87.5%) patients had good triceps strength. The average range of motion was 118.4 ± 7 degrees (range 80°-130°). The average time to union was 3.2 ± 1.6 months (range two to six months). No patient had triceps rupture, implant failure, neurovascular deficit or nonunion. Two patients needed removal of the implant because of subcutaneous prominence. The TRAP approach provides good visualization for fixation of intercondylar fractures of the humerus, without any noticeable untoward effect on triceps strength and postoperative rehabilitation; and one can avoid iatrogenic fracture of the olecranon and its associated complications.


Further oxidation of hydroxycalcidiol by calcidiol 24-hydroxylase. A study with the mature enzyme expressed in Escherichia coli.
The coding region of the cDNA for rat kidney calcidiol 24-hydroxylase (P450cc24), which is involved in calcium homeostasis in animals, was inserted into an expression vector pKK223-3. The recombinant plasmid was formed in a specific manner without deletion or substitution of any parts of the coding region of the cDNA. When the resulting plasmid was introduced into Escherichia coli JM109, the recombinant cells produced a protein which was immunoreactive to an antibody against P450cc24. When the cell-free extract of the transformed cells was incubated with calcidiol together with bovine adrenodoxin and NADPH-adrenodoxin reductase, not only hydroxycalcidiol but also other metabolites such as oxocalcidiol and oxohydroxycalcidiol were produced. Similarly, calcitriol was converted not only to calcitetrol but also to oxocalcitriol and oxohydroxycalcitriol. These results indicate that a single enzyme expressed in the bacteria is responsible for all these successive reactions.


Cognitive Factors Affecting Freeze-like Behavior in Humans.
Contemporary research on survival-related defensive behaviors has identified physiological markers of freeze/flight/fight. Our research focused on cognitive factors associated with freeze-like behavior in humans. Study 1 tested if an explicit decision to freeze is associated with the psychophysiological state of freezing. Heart rate deceleration occurred when participants chose to freeze. Study 2 varied the efficacy of freezing relative to other defense options and found "freeze" was responsive to variations in the perceived effectiveness of alternative actions. Study 3 tested if individual differences in motivational orientation affect preference for a "freeze" option when the efficacy of options is held constant. A trend in the predicted direction suggested that naturally occurring cognitions led loss-avoiders to select "freeze" more often than reward-seekers. In combination, our attention to the cognitive factors affecting freeze-like behavior in humans represents a preliminary step in addressing an important but neglected research area.


Photoradiation therapy. II. Cure of animal tumors with hematoporphyrin and light.
Exposure of mouse and rat tumors of various types to more than 600 nm light 24 or 48 hours after an injection of hematoporphyrin resulted in a substantial number of long-term cures. Since hematoporphyrin is preferentially retained in tumor tissue, selective tumor destruction could be obtained. Light penetration studies and the high efficiency of this technique indicated its applicability even to certain deep-seated human tumors.


Cancer Metabolism under Limiting Oxygen Conditions.
Molecular oxygen (O2) is essential for cellular bioenergetics and numerous biochemical reactions necessary for life. Solid tumors outgrow the native blood supply and diffusion limits of O2, and therefore must engage hypoxia response pathways that evolved to withstand acute periods of low O2 Hypoxia activates coordinated gene expression programs, primarily through hypoxia inducible factors (HIFs), to support survival. Many of these changes involve metabolic rewiring such as increasing glycolysis to support ATP generation while suppressing mitochondrial metabolism. Since low O2 is often coupled with nutrient stress in the tumor microenvironment, other responses to hypoxia include activation of nutrient uptake pathways, metabolite scavenging, and regulation of stress and growth signaling cascades. Continued development of models that better recapitulate tumors and their microenvironments will lead to greater understanding of oxygen-dependent metabolic reprogramming and lead to more effective cancer therapies.


A technique of silver impregnation for nervous tissues with some thiocyanates.
Taking advantage of some properties of thiocyanates, a technique of silver impregnation for nerve fibres in the human central nervous system is described. The following procedure is suggested: frozen sections 25-35 micrometer thick, 5-10% aqueous solution of ammonium thiocyanate or potassium thiocyanate, 10% aqueous solution of silver nitrate, ammoniacal silver solution, reduction in 20% formalin, gold toning, dehydrating and mounting. By this procedure, fine fibres appear in the color range from purple to dark purple on the almost colorless background.


The role of MR imaging with half Fourier acquired single shot turbo spin echo sequence in the diagnosis of lung lesions in comparison with multislice CT.
To compare the diagnostic values of magnetic resonance imaging using Half Fourier Acquired Single Shot Turbo Spin Echo sequence and multidetector computed tomography in patients with pathologically examined pulmonary lesions. The retrospective, descriptive study was conducted at Radiology Department, Diskapi Research Hospital, Ankara, Turkey, and comprised records of patients with pathologically examined pulmonary lesions between May 2009 and March 2012. Patients were divided into three groups and examined by both multidedector computed tomography and magnetic resonance imaging. During the imaging, patients were not administered any intravenous contrast medium. Electrocardiogram gating and breath holding were not performed in echo sequence. Pulmonary lesions were evaluated on the basis of their dimensions, numbers, differentiation from atelectasis and consolidation, invasion to the thoracic wall-mediastinal structures and presence of lymphadenopathies. Sensitivity of all patients was 50% (p = 0.214) and specificity of CT and MRI were 82.5% (p = 0.134) for the detectability of submilimetric nodules. For differentiation of the mass from atelectasis and consolidation, the sensitivity of computed tomography was statistically more significant compared to magnetic resonance imaging (86.6%; p = 0.035). For the invasion of the mass to the mediastinal structures and the thoracic wall, the sensitivity of magnetic resonance imaging was statistically more significant compared to tomography (86.6%; p = 0.035). HASTE sequence can be used to determine the invasion of the pulmonary mass to the mediastinal structures and the thoracic wall since it is more sensitive than computed tomography. It can also be used to detect submilimetric nodules. It has equal sensitivity and specificity compared to computed tomography. But computed tomography is superior for the differentiation of the mass from atelectasis and consolidation.


[Insulin secretion and insulin resistance].
Aging is a critical risk factor for impaired glucose tolerance and diabetes. In Japan, 8.9 million people are reported to have diabetes, and 37% of those are over the age of 70. In this review, we summarize the current evidence on how aging affects pancreatic beta cell function, beta cell mass, insulin secretion and insulin sensitivity. The pathogenesis of type 2 diabetes (T2DM) in aging is characterized by two major features: impaired insulin secretion and peripheral insulin resistance. Understanding the mechanism that lead to impaired glucose homeostasis and T2DM in the elderly will lead to development of novel treatments that will prevent or delay diabetes, substantially improve quality of life and ultimately increase overall life span.


Screen-time influences children's mental imagery performance.
Mental imagery is a foundational human faculty that depends on active image construction and sensorimotor experiences. However, children now spend a significant proportion of their day engaged with screen-media, which (a) provide them with ready-made mental images, and (b) constitute a sensory narrowing whereby input is typically focused on the visual and auditory modalities. Accordingly, we test the idea that screen-time influences the development of children's mental imagery with a focus on mental image generation and inspection from the visual and haptic domains. In a longitudinal cross-lagged panel design, children (n = 266) aged between 3 and 9 years were tested at two points in time, 10 months apart. Measures of screen-time and mental imagery were employed, alongside a host of control variables including working memory, vocabulary, demographics, device ownership, and age of exposure to screen-media. Findings indicate a statistically significant path from screen-time at time 1 to mental imagery at time 2, above and beyond the influence of the control variables. These unique findings are discussed in terms of the influence of screen-time on mental imagery.


Embryonic fibroblasts represent a connecting link between mesenchymal and embryonic stem cells.
It is well established that fibroblasts and mesenchymal stem cells (MSC) share several characteristics with subtle differences. However, no study highlighting the versatility of fibroblasts beyond their multipotentiality has been reported so far. Mouse embryonic fibroblasts (MEFs) are widely used as feeder layers to support the growth of embryonic stem cells (ESC). We hypothesized that MEF may retain ES-like features in concurrence to their developmental hierarchy in addition to their multipotent nature. Hence, we performed a comparative assessment of MEF and ESC to determine their ability to differentiate into cell types other than mesoderm as well as capacity to form teratoma using routine in vitro and in vivo techniques. MEF were derived by trypsin/ EDTA (ethylenediaminetetraacetic acid) digestion from E13.5 embryos after removing heads and viscera following plastic adherence. MEFs robustly proliferated in culture until passage 15 and formed aggregates by hanging drop method. Flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry revealed the presence of key MSC markers such as CD90, CD73, Sca-1, CD44, CD29, Vimentin and absence of CD45. Additionally, they expressed SSEA-1, Oct-4, Nanog, Sox-2 and ABCG2 as pluripotency markers; Nestin, β-III tubulin, Otx-2 (ectoderm); MEF-2, Mesp2, GATA-2 (mesoderm) and GATA-4, α-amylase, PDX-1 (endoderm) as tri-lineage markers. Furthermore, MEFs formed representative tissues from all three germ layers upon transplantation into Balb/c mice. These unique abilities of MEF to exhibit pluripotency, in addition to fibroblast characteristics and their ready availability with less ethical concerns and low maintenance requirements make them an attractive model for further exploration as a possible tool for regenerative medicine.


Draft Genome Sequence of a Bacteroides fragilis Strain Isolated from Peritoneal Fluid of a Patient from Kazakhstan.
Here, we report the draft genome sequence of Bacteroides fragilis strain KZ02, isolated from a patient with peritonitis hospitalized in a health facility in Nur-Sultan, Kazakhstan. The genome of the strain contains 4,103 protein-coding genes, including the cepA gene, which causes resistance to beta-lactam antibiotics.


Differential Effects of Valence and Encoding Strategy on Internal Source Memory and Judgments of Source: Exploring the Production and the Self-Reference Effect.
Item memory studies show that emotional stimuli are associated with improved memory performance compared to neutral ones. However, emotion-related effects on source memory are less consistent. The current study probed how emotional valence and specific encoding conditions influence internal source memory performance and judgments of source (JOSs). In two independent experiments, participants were required to read silently/aloud (Experiment 1) or to perform self-reference/common judgments (Experiment 2) on a list of negative/neutral/positive words. They also performed immediate JOSs ratings for each word. The study phase was followed by a test phase in which participants performed old-new judgments. In Experiment 1, the production effect was replicated for item memory, but the effects of valence on item and source memory were not significant. In Experiment 2, self-referential processing effects on item and source memory differed as a function of valence. In both experiments, JOSs ratings were sensitive to valence and encoding conditions, although they were not predictive of objective memory performance. These findings demonstrate that the effects of valence on internal source memory and JOSs are modulated by encoding strategy. Thus, the way information is encoded can shed light on how emotion might enhance, impair or exert no influence on source memory.


The relaxant action of betaxolol on isolated bovine retinal microarteries.
We investigated the possible effects on retinal blood flow of betaxolol, a beta blocker which is used as antiglaucomatous medication. Ring segments of retinal microarteries were isolated from bovine eyes and mounted in an organ bath for measurement of contractile force. The effects of betaxolol were studied during K(+)-, stretch-, and serotonin-induced contractions, to enable comparison to the effects of the standard beta blocker propranolol and the Ca2+ channel blocker verapamil. Betaxolol relaxed K(+)-induced contractions in a dose-dependent manner. The drug relaxed the phasic part of the K(+)-induced contractions more than the tonic part. Betaxolol had no effect on stretch-induced contractions. The tonic part of the serotonin-induced contractions showed a trend to decrease in response to betaxolol. These highly specific effects of betaxolol resembled the effects of propranolol. Since betaxolol has significantly less membrane stabilizing activity than has propranolol, this activity is not responsible for the relaxant action of beta blockers on retinal microarteries. The action of both beta blockers resembled the action of the Ca2+ channel blocker verapamil.


[Effects of cattle encephalon glycoside and ignotin injection on serum level of S100B protein and neuron specific enolase in patients undergoing cardiac valve replacement with cardiopulmonary bypass].
To investigate the effects of cattle encephalon glycoside and ignotin injection on serum level of S100B protein and neuron specific enolase (NSE) during cardiac valve replacement with cardiopulmonary bypass (CPB). Forty patients undergoing cardiac valve replacement with CPB were randomly divided into two equal groups: cattle encephalon glycoside and ignotin injection group (Group A, injected intravenously with cattle encephalon glycoside and ignotin 20 ml after induction of anesthesia, and control group (Group B, injected intravenously with normal saline instead. Blood samples were taken from the jugular bulb after induction of anesthesia (T1), immediately, and 2 h, 6 h, and 24 h after the discontinuation of CPB (T2, T3, T4, and T5) for determination of serum levels of S100B protein and NSE. The serum levels of S100B protein and NSE of both groups were significantly increased after CPB, and then gradually decreased. At the time point T5, the serum levels of S100B protein of both groups decreased to near the baseline levels (T1 levels), but the serum levels of NSE remained high in both groups. At the time points T2, T3, T4 and T5, the serum levels of S100B protein were significantly higher in Group B than in Group A (all P < 0.05). At the time points T2, T3, and T4, the serum levels of NSE was significantly higher in Group B than in Group A (all P < 0.05). Cattle encephalon glycoside and ignotin injection decreases the serum levels of S100B protein and NSE and has cerebral protective effect during cardiac valve replacement with CPB to a certain degree.


[Dynamics of indicators of dermocytograms and reparative capacity of the body in burns].
The investigation of dermocytograms by a modified method of the "skin window" in 101 patients with different square surfaces of deep burns has shown that the dynamics of mononuclear content is dependent on the injury degree. Lower parameters of mononuclear content in dermocytograms during the course of treatment correspond to the disturbance of reparative capacities of the organism in groups of patients with the complicated course of the disease. The "skin window" test can be used for the treatment since it shows the degree of the burn trauma dynamics and character of its course, facilitates the prognosis of complications.


Partner-specific sexual behaviors among persons with both main and other partners.
If men and women engage in different sexual behavior with main partners than with other types of partners, then programs aimed at preventing the spread of sexually transmitted diseases (STDs) may need to address individuals' differential risk with each partner type. Relationship characteristics, partner risk behaviors and sexual behaviors are examined among 123 male and 106 female STD clinic patients who had both main and other partners. Individual-level comparisons are made for two types of partner pairs: main vs. other frequent (side) partners and main vs. casual partners. Among men and women with both main and side partners, the proportion who had known only their main partner for at least a year (48% of men and 41% of women) was significantly higher than the proportion who had known only their side partner for that long (2% and 9%, respectively); no other variable differed significantly by partner type. Among those with main and casual partners, both men and women were more likely to use alcohol or drugs before or during sex with main partners only (15%) than with casual partners only (1-3%). Women with main and casual partners were more likely to have oral sex only with main partners than only with casual partners (37% vs. 3%), and were more likely to use condoms only with casual partners than only with main partners (33% vs. 4%). Providers need to ask individuals about their sexual behaviors with different partner types, and should tailor prevention messages to an individual's risks and reproductive intentions with each partner.


An unusual isotope effect in a high-transition-temperature superconductor.
In conventional superconductors, the electron pairing that allows superconductivity is caused by exchange of virtual phonons, which are quanta of lattice vibration. For high-transition-temperature (high-T(c)) superconductors, it is far from clear that phonons are involved in the pairing at all. For example, the negligible change in T(c) of optimally doped Bi2Sr2CaCu2O8+delta (Bi2212; ref. 1) upon oxygen isotope substitution (16O --> 18O leads to T(c) decreasing from 92 to 91 K) has often been taken to mean that phonons play an insignificant role in this material. Here we provide a detailed comparison of the electron dynamics of Bi2212 samples containing different oxygen isotopes, using angle-resolved photoemission spectroscopy. Our data show definite and strong isotope effects. Surprisingly, the effects mainly appear in broad high-energy humps, commonly referred to as 'incoherent peaks'. As a function of temperature and electron momentum, the magnitude of the isotope effect closely correlates with the superconducting gap--that is, the pair binding energy. We suggest that these results can be explained in a dynamic spin-Peierls picture, where the singlet pairing of electrons and the electron-lattice coupling mutually enhance each other.


Migratory large vessel vasculitis preceding acute myeloid leukemia: a case report.
Large vessel vasculitis is a rare disorder usually occurring in the context of the autoimmune conditions of giant cell arteritis and Takayasu's arteritis. Case reports have described large vessel vasculitis occurring in individuals with myelodysplastic syndrome, preceding transformation to acute myeloid leukemia. A 56-year-old Afghanistan-born woman presented with fever, a tender left carotid artery, and raised inflammatory markers. Computed tomography revealed thickening of the wall of her left carotid artery. Her symptoms resolved spontaneously; however, they recurred weeks later on the contralateral side, along with abdominal pain after eating. Further imaging with computed tomography and positron emission tomography demonstrated resolution of her left carotid artery abnormality, but new wall thickening and inflammation in her right carotid artery, abdominal aorta, and superior mesenteric artery. She was diagnosed as having large vessel vasculitis, which resolved with corticosteroids and methotrexate. Five months later, she developed acute myeloid leukemia. She had no known history of myelodysplastic syndrome at the time of diagnosis with vasculitis. Large vessel vasculitis in older individuals presenting with atypical clinical features, such as a migratory pattern of affected vessels, vessel wall tenderness, and marked systemic inflammation, should prompt a search for underlying myelodysplasia. Clinicians should be vigilant for progression to acute myeloid leukemia.


Psychosomatic aspects of arterial hypertension in women.
Arterial hypertension is one of the most widespread diseases in the world, both in women and men. In Poland, about 45% of the adult population suffers from arterial hypertension--it afflicts 45% of men and 36-38% of women. Arterial hypertension is a set of regulatory disorders of a complicated, multifactor etiology encompassing genetic conditions, the influence of the environment and some individual factors. Being also psychosomatic disorder it is strongly linked with improper adaptation to stress, personality traits and behavioural conditions esspecially with the type A behaviour pattern. This type of behaviour includes a strong need of achievement a tendency to dominate, and aggressiveness. The type A women--impatient, aggressive, hostile to their environment, committed to work and competitive--have a higher CVR (cardiovascular reactivity) coefficient and higher arterial blood pressure than type B. Some authors suggest that the lowering of estrogen levels in women over the age of 50 increases the frequency of occurrence of arterial hypertension. In spite of the fact that we do not have a full knowledge of the mechanisms starting the reaction chain, the awareness of these factors can help us decrease the risk of the development of the disease or hinder its progression.


Metanephric stromal tumor with BRAF V600E mutation in an adult patient: Case report and literature review.
Metanephric stromal tumor (MST) is a rare, benign pediatric renal neoplasm of uncertain histogenesis that belongs to the metanephric family of tumors. MST involving adult patients is very uncommon, which could cause significant diagnostic confusions. Recent molecular studies have revealed recurrent BRAF mutations in MST in pediatric patients which may serve as powerful diagnostic tools for distinguishing MST from other renal stromal tumors. We present a BRAF-mutated MST in an adult patient with a brief review of the pertinent literature. To our knowledge, our case represents to date the sixth report of adult MST and the first adult MST proven to harbor BRAF mutation. This is a 41-year-old man who was incidentally identified to have a left renal mass by ultrasonography. He had a 5-year history of hypertension which could be controlled with oral antihypertensive drug. Partial nephrectomy was performed which demonstrated a 2.6-cm, oval, circumscribed mass with a fibrotic and firm texture. Microscopic examination showed a hypocellular, spindle cell neoplasm with entrapped nephrons, within a predominantly fibrous and focally myxoid stroma. Foci of hyalinized stroma surrounding entrapped native renal tubules or blood vessels to form concentric collarettes-like structures, and small-sized arterioles showing angiodysplasia, were observed. Immunostains showed the tumor cells to be diffusely positive for CD34. Fluorescence in-situ hybridization analysis was negative for rearrangements involving both the EWSR1 and FUS loci. Targeted next-generation sequencing disclosed a pathogenic mutation of BRAF exon15: c.1799T>A (p.V600E). The patient's hypertension normalized without oral antihypertensive drugs 2 months postoperatively and he was in good status 12 months after the surgery. Our case highlights the diagnostic dilemma of MST occurring in adults and points to the usefulness of molecular detection of BRAF mutation for arriving at accurate diagnosis.


Chicory fructans in pig diet reduce skatole in back fat of entire male pigs.
Androstenone, skatole and indole are main compounds responsible for boar taint, an off-odour in meat of some entire male pigs. Several feed ingredients derived from chicory have been reported to reduce fat skatole levels, while results for indole are more contradictory. The skatole-reducing effect is probably based on the prebiotic effects described for fructan compounds. Inulin and oligofructose have a high and low degree of polymerization, respectively. The fermentation rate decreases with an increasing degree of polymerization, which may result in differing effects of the compounds on skatole and/or indole levels. In this study we evaluated the effect of the inclusion of 5% inulin or 5% oligofructose during the last 3weeks before slaughter on carcass quality, concentration of skatole and indole in back fat as well as on the olfactory evaluation of boar taint in fat. Carcass weight did not differ between treatment groups but lean meat percentage increased when feeding oligofructose (P=0.019) compared to the control group, which is relevant for further research. Inclusion of 5% inulin or 5% oligofructose in the finisher diet of entire male pigs significantly reduced the back fat skatole concentration, without influence on indole. Olfactory score for boar taint tended to decrease when oligofructose was added to the diet.


The Dartmouth Dementia Directive: Experience with a Community-Based Workshop Pilot of a Novel Dementia-Specific Advance Directive.
Dementia is a growing issue at the end of life that presents unique challenges for advance care planning. Advance directives are a useful and important component of end-of-life planning, but standard advance directives have less utility in cases of loss of capacity due to dementia. An advance directive designed to specifically address end-of-life issues in the setting of dementia can provide patients with increased autonomy and caregivers with improved information about the desires of the individual in question. The Dartmouth Dementia Directive is a dementia-specific advance directive, available online, that seeks to address common concerns of individuals who are planning for dementia-related end-of-life care. This directive was piloted in a community-based workshop, which provided important details and perspective on the best use of dementia-specific advance directives in the greater population.


Correcting large lens radial distortion using epipolar constraint.
It is necessary to correct lens distortion for building 3D models from multiple 2D images. Lens distortion is usually dominated by radial components, and especially dominated by the first radial distortion term that is called large lens radial distortion. In this work, we propose a method for correcting large lens radial distortion based on epipolar constraint. It requires nothing but a number of image point correspondences from two views, while the distortion center is assumed to be at the image center. Experimental results show that the robustness and correction accuracy of the proposed method outperform those of the previous methods.


A Conformable Ultrasound Patch for Cavitation-Enhanced Transdermal Cosmeceutical Delivery.
Increased consumer interest in healthy-looking skin demands a safe and effective method to increase transdermal absorption of innovative therapeutic cosmeceuticals. However, permeation of small-molecule drugs is limited by the innate barrier function of the stratum corneum. Here, a conformable ultrasound patch (cUSP) that enhances transdermal transport of niacinamide by inducing intermediate-frequency sonophoresis in the fluid coupling medium between the patch and the skin is reported. The cUSP consists of piezoelectric transducers embedded in a soft elastomer to create localized cavitation pockets (0.8 cm2 , 1 mm deep) over larger areas of conformal contact (20 cm2 ). Multiphysics simulation models, acoustic spectrum analysis, and high-speed videography are used to characterize transducer deflection, acoustic pressure fields, and resulting cavitation bubble dynamics in the coupling medium. The final system demonstrates a 26.2-fold enhancement in niacinamide transport in a porcine model in vitro with a 10 min ultrasound application, demonstrating the suitability of the device for short-exposure, large-area application of sonophoresis for patients and consumers suffering from skin conditions and premature skin aging.


The Role of Biologics in the Management of Asthma in the Pediatric Patient.
The management of pediatric patients with asthma continues to be a major health issue. For many patients, traditional therapies have been very effective, but for a large number of patients asthma remains poorly controlled. This leads to significant morbidity and impairment to quality of life. Recently, several new biologics, as well as new dosage forms of combination inhaled drugs, have been made available for use adding to the armamentarium of therapy for specific asthma phenotypes. Biologics have shown promise in the more difficult to manage asthma patient. Approved in children, omalizumab, an anti-immunoglobulin E (anti-IgE) antibody, has been available for several years. New agents, like mepolizumab and benralizumab, directed against interleukin (IL) 5, have indications for children >6 and >12 years of age, respectively. Dupilumab, an IL-4- and IL-13-directed antibody, has been studied as well in eosinophilic asthma, with positive results. A thorough understanding of the clinical data of these agents is key, as they may greatly improve the quality of life in children with difficult-to-manage asthma.


On the origin of the FcRIII (CD16)-containing vesicle population in human neutrophil granulocytes.
Human blood neutrophils bear two types of Fc receptors that recognize the Fc portion of immunoglobulin G: FcRII and FcRIII. In earlier studies we found that neutrophils not only express FcRIII on their plasma membrane but also contain a large population of FcRIII-containing vesicles mainly located in the juxtanuclear area. To find out whether these vesicles derive from the plasma membrane, we used electron microscopic techniques to study compartments involved in ligand-independent endocytosis in human neutrophil granulocytes. The endocytic compartments were labeled with BSA-gold. This marker entered the cell through non-coated invaginations of the plasma membrane as well as via coated pits. After internalization, BSA-gold was present in numerous electron-lucent vesicles in the juxtanuclear area and in the trans-Golgi reticulum, endosomes, and lysosome-like structures. FcRIII also occurred in the BSA-gold-containing electron-lucent vesicles in the juxtanuclear area, as shown by postembedding immunocytochemical labeling of FcRIII in cells already containing BSA-gold. Quantification showed that 29% of all FcRIII-containing vesicles also bear BSA-gold while the remaining 71% contain only the receptor. In sum, our findings show that one third of the FcRIII-containing electron-lucent vesicles in neutrophil granulocytes derive from the plasma membrane and are involved in ligand-independent endocytosis of FcRIII. The majority of these vesicles, however, are not of an endocytic origin and might constitute an "internal pool" of receptors in these cells.


Role of operon aaoSo-mutT in antioxidant defense in Streptococcus oligofermentans.
Previously, we have found that an insertional inactivation of aao(So), a gene encoding L-amino acid oxidase (LAAO), causes marked repression of the growth of Streptococcus oligofermentans. Here, we found that aao(So) and mutT, a homolog of pyrophosphohydrolase gene of Escherichia coli, constituted an operon. Deletion of either gene did not impair the growth of S. oligofermentans, but double deletion of both aao(So) and mutT was lethal. Quantitative PCR showed that the transcript abundance of mutT was reduced for 13-fold in the aao(So) insertional mutant, indicating that gene polarity derived from the inactivation of aao(So) attenuated the expression of mutT. Enzymatic assays were conducted to determine the biochemical functions of LAAO and MutT of S. oligofermentans. The results indicated that LAAO functioned as an aminoacetone oxidase [47.75 nmol H(2)O(2) (min · mg protein)(-1)]; and MutT showed the pyrophosphohydrolase activity, which removed mutagens such as 8-oxo-dGTP. Like paraquat, aao(So) mutations increased the expression of SOD, and addition of aminoacetone (final concentration, 5 mM) decreased the mutant's growth by 11%, indicating that the aao(So) mutants are under ROS stress. HPLC did reveal elevated levels of cytoplasmic aminoacetone in both the deletion and insertional gene mutants of aao(So). Electron spin resonance spectroscopy showed increased hydroxyl radicals in both types of aao(So) mutant. This demonstrated that inactivation of aao(So) caused the elevation of the prooxidant aminoacetone, resulting the cellular ROS stress. Our study indicates that the presence of both LAAO and MutT can prevent endogenous metabolites-generated ROS and mutagens. In this way, we were able to determine the role of the aao(So)-mutT operon in antioxidant defense in S. oligofermentans.