Profiling changes in gait dynamics resulting from progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced nigrostriatal lesioning.
Current behavioral measurements for motor impairment are not consistently sensitive in rodent models of partial nigrostriatal dopamine (DA) depletion. In addition to exploratory and somatosensory behavior, motor skills that are thought to be directly translatable to human Parkinson's disease patients are assessed. However, many of these motor tests require the training and learning of particular tasks, so it cannot be determined whether impairments are due to motor or to learning deficit. Therefore, we have quantified multiple temporal and spatial indices of gait dynamics in a model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced partial nigrostriatal lesioning using a treadmill apparatus requiring no prior training. Three days following the cessation of progressively increased MPTP administration, rearing and foot-fault behaviors showed significant deficit. Ten days after the final MPTP injection, gait dynamics were assessed and indicated differences between MPTP- and vehicle-treated animals. The major significant changes were in stride length, frequency, duration, and number of steps. Three weeks following a progressively increased dose of MPTP (administered 5 days per week over the course of 4 weeks), mice showed a 63% decrease in tyrosine hydroxylase-immunoreactive (TH-ir) nigrostriatal neurons in the substantia nigra pars compacta and a 72% decrease in TH-ir terminals in the caudate-putamen. This suggests that there is a continued effect of progressively increased MPTP on nigrostriatal DA neurons, correlated with rearing and foot-fault behaviors and further characterized by differences in temporal and spatial measurements of gait dynamics.


Measurement of the proliferative activity of three different sublines of the Dunning rat prostate tumor R3327.
The development of the BrdUrd assay has greatly facilitated the measurement of proliferation in both human and experimental tumors. The potential doubling time (Tpot) was reported to be the most promising parameter to serve as a predictive assay to select patients for new treatment modalities such as accelerated fractionation and fast neutrons. We compared flow cytometry and immunochemistry applied to three sublines of the Dunning rat prostate tumor with differing differentiation. The anaplastic R3327-AT subline has a labeling index (LI) of 7 +/- 0.5% and 8.8 +/- 3.7 measured with flow cytometry and histology respectively, S-phase duration (Ts) of 8 h, a Tpot of 4.7 days and a cell loss factors (phi) of 15%. Proliferating cells are homogeneously distributed. The moderately well differentiated R3327-HI subline shows a LI of 5% (flow cytometry 5 +/- 0.5%, immunohistochemistry 5 +/- 2%), Ts of 10.7 h, Tpot of 8.9 days and phi of 10%. The well differentiated subline R3327-H has two cell populations (DNA-index 1.6) and a labeling index of 3.7 +/- 0.5% measured with flow cytometry and 2.2 +/- 0.4% with immunochemistry.


Prostate-specific antigen: questions often asked.
In conclusion, an effective new marker for prostatic tissue has been identified and is commonly known as PSA. A review of the literature indicates that although PSA is not tumor specific, its organ-site and cell-type specificity provide the basis for making PSA the marker of choice for use in patients with prostate cancer. The clinical utility of PSA includes monitoring therapeutic efficacy, screening and early diagnosis in high-risk patients, prognosis, staging, and tumor volume evaluation, prediction of disease progression, detection of recurrent disease after radical prostatectomy, and the differential diagnosis and confirmation of tissue for prostatic origin. PSA is not a "magic bullet" for patients with prostate cancer. Many questions must still be answered. For example, with an increase in sensitivity for screening of high-risk populations, how does the urologist/oncologist determine which patients with latent curable early cancer will develop into clinically significant metastasis? Is PSA a more reliable method for detection of early prostate cancer than rectal examination? What procedure should be followed for an asymptomatic patient who presents a 35 ng/ml level of PSA during a routine physical examination? Clearly, further studies are required to answer these questions as well as to assess the malignant potential of the prostatic tumor cell. For now, the combination of PSA, rectal examination, and transrectal ultrasonography guided needle biopsy would appear to be the method of choice to decrease the yearly fatalities due to cancer of the prostate.


Production of interferon gamma in asthmatic patients with small bacille Calmette-Guerin scars: a pilot study.
Some studies suggest a decrease in interferon (IFN) gamma production among atopic individuals, and others refer to low IFN-gamma levels as a characteristic of asthma, regardless of the atopic state. Recent research has indicated a relation between asthma and a tendency toward a bacille Calmette-Guerin (BCG) vaccine scar with a small diameter, suggesting an association of this illness with the low production of IFN-gamma. The aim of this study was to check the hypothesis that asthmatic patients with a small BCG scar present low IFN-gamma production. This work was a quasi-experimental study. The capacity to produce IFN-gamma among 12 asthmatic patients with an average BCG vaccine scar diameter <5 mm was compared with 7 nonasthmatic individuals with scars > or =5 mm using whole blood cells stimulated by purified protein derivative (PPD), phorbol myristate acetatelionomycin (PMA/Iono) and medium (no stimulus). The study also analyzed the relation between IFN-gamma production after PPD stimulation and eosinophil count, total IgE, and dust-mite-specific IgE levels. The asthmatic patients presented a decrease in IFN-gamma production in comparison with a control group after PPD stimulation (p < 0.02). However, the same was not observed when PMA/Iono stimulation was used or when no stimulation was used. Asthmatic patients with small BCG scars showed a decrease in IFN-gamma production, suggesting that there may be an intrinsic characteristic of these patients.


Multicomponent lifetime-based pH sensors utilizing constant-lifetime probes.
A multicomponent luminescent sensor system is described that uses probe species with constant lifetimes to generate an analyte-dependent change in the apparent sensor lifetime. This new sensing scheme not only allows for lifetime-based measurement techniques to be applied to sensors that employ static quenching interactions but also provides the ability to vary the sensitivity of the sensor system with simple changes in instrumental parameters. A model for the multicomponent sensor is presented, followed by data measured using a prototype pH sensor based on the model.


Controlling the stability and size of double-emulsion-templated poly(lactic-co-glycolic) acid microcapsules.
The stability and size of poly(lactic-co-glycolic)acid (PLGA)-containing double emulsions and the resulting PLGA microcapsules are controlled by varying the composition of highly monodisperse water-in-oil-in-water (W/O/W) double emulsions. We propose that the basic inner phase of W/O/W double emulsions catalyzes the hydrolysis of PLGA and the ionization of carboxylic acid end groups, which enhances the surface activity of PLGA and facilitates the stabilization of the double emulsions. The size of PLGA-containing double emulsions and that of resulting microcapsules can be readily tuned by osmotic annealing, which depends on the concentration ratio of a solute in the inner and outer phases of double emulsions. The internal volume of PLGA microcapsules can be changed by more than 3 orders of magnitude using this method. This approach also overcomes the difficulty in generating monodisperse double emulsions and microcapsules over a wide range of dimensions using a single microfluidic device. The osmotic annealing method can also be used to concentrate encapsulated species such as colloidal suspensions and biomacromolecules.


Texture and Color Enhancement Imaging Improves Colonic Adenoma Detection: A Multicenter Randomized Controlled Trial.
The global burden of colorectal cancer is expected to increase more than 60% by 2030; however, compelling evidence now shows that the implementation of population screening programs in developed countries has led to a substantial reduction in incidence and mortality.1,2 Despite this, patients continue to develop preventable colorectal cancers, in part because of high rates of interval colon cancer diagnosed after screening or surveillance colonoscopies.3.


The Direction of Neurosurgery to Overcome the Living with COVID-19 Era : The Possibility of Telemedicine in Neurosurgery.
Due to the implementation of vaccinations and the development of therapeutic agents, the coronavirus disease 2019 (COVID-19) pandemic that started at the end of 2019 has entered a new phase. As a result, neurosurgeons should reconsider the way they treat their patients. As the COVID-19 situation prolongs, the change in neurosurgical emergency patients according to the number of confirmed cases is no longer clear. Outpatient treatment by telephone was permitted according to government policy. In addition, visits to caregivers in the intensive care unit were limited. The electronic medical records of patients who had been treated over the phone for a month (during April 2020, while the hospital was closing) were reviewed. Meanwhile, according to the limited visits to the intensive care unit, a video meeting was held with the caregivers. After the video meeting, satisfaction was evaluated using a questionnaire. During April 2020, 1021 patients received non-face-to-face care over the telephone. Among the patients, no critical medical problem occurred due to non-face-to-face care. From July 2021 to December 2021, 321 patients were admitted to the neurosurgical intensive care unit and 107 patients (33.3%) including their caregivers agreed to video visits. Twice a week, advance notice was given that access would be made through a mobile device and the nurse explained to caregivers how to use the mobile device. The time for the video meeting was approximately 20 minutes per patient. Based on the questionnaire, 81 respondents (75.7%) answered that they agreed, and 26 respondents (24.3%) answered that they strongly agreed that was easy to communicate through video meetings. Fifty-two (48.6%) agreed and 55 (51.4%) strongly agreed that they were easy to understand the doctor's explanation. For overall satisfaction with this video meeting, three respondents (2.8%) gave 4/5 points and 95 respondents (88.8%) gave 5/5 points, and nine (8.4%) gave 3/5 points. Their reason was that there was not enough time. In situations where patient visits are limited, video meetings through a mobile device can provide sufficient satisfaction to caregivers. Telemedicine will likely become common in the near future. Health care professionals should prepare and respond to these needs and changes. Therefore, establishing a system with institutional support is necessary.


Further evidence for the tetraoxoiodate(V) anion, IO(4)(3-): hydrothermal syntheses and structures of Ba[(MoO(2))(6)(IO(4))(2)O(4)] x H(2)O and Ba(3)[(MoO(2))(2)(IO(6))(2)] x 2H(2)O.
The hydrothermal reaction of MoO(3) with BaH(3)IO(6) at 180 degrees C for 3 days results in the formation of Ba[(MoO(2))(6)(IO(4))(2)O(4)] x H(2)O (1). Under similar conditions, the reaction of Ba(OH)(2) x 8H(2)O with MoO(3) and Ba(IO(4))(2) x 6H(2)O yields Ba(3)[(MoO(2))(2)(IO(6))(2)] x 2H(2)O (2). The structure of 1, determined by single-crystal X-ray diffraction, consists of corner- and edge-sharing distorted MoO(6) octahedra that create two-dimensional slabs. Contained within this molybdenum oxide framework are approximately C(2v) tetraoxoiodate(V) anions, IO(4)(3-), that are involved in bonding with five Mo(VI) centers. The two equatorial oxygen atoms of the IO(4)(3-) anion chelate a single Mo(VI) center, whereas the axial atoms are mu(3)-oxo groups and complete the octahedra of four MoO(6) units. The coordination of the tetraoxoiodate(V) anion to these five highly electropositive centers is probably responsible for stabilizing the substantial anionic charge of this anion. The Ba(2+) cations separate the layers from one another and form long ionic contacts with neighboring oxygen atoms and a water molecule. Compound 2 also contains distorted MoO(6) octahedra. However, these solely edge-share with octahedral hexaoxoiodate(VII), IO(6)(5-), anions to form zigzagging one-dimensional, (1)(infinity)[(MoO(2))(IO(6))](3-), chains that are polar. These chains are separated from one another by Ba(2+) cations that are coordinated by additional water molecules. Bond valence sums for the iodine atoms in 1 and 2 are 5.01 and 7.03, respectively. Crystallographic data: 1, monoclinic, space group C2/c, a = 13.584(1) A, b = 7.3977(7) A, c = 20.736(2) A, beta = 108.244(2) degrees, Z = 4; 2, orthorhombic, space group Fdd2, a = 13.356(7) A, b = 45.54(2) A, c = 4.867(3) A, Z = 8.


Identification of Fatty Acid Glucose Esters as Os9BGlu31 Transglucosidase Substrates in Rice Flag Leaves.
Rice Os9BGlu31 transglucosidase transfers glucosyl moieties between various carboxylic acids and alcohols, including phenolic acids and flavonoids, in vitro. The role of Os9BGlu31 transglucosidase in rice plant metabolism has only been suggested to date. Methanolic extracts of rice bran and leaves were found to contain oleic acid and linoleic acid to which Os9BGlu31 could transfer glucose from the 4-nitrophenyl β-D-glucoside (4NPGlc) donor to form 1-O-acyl glucose esters. Os9BGlu31 showed higher activity with oleic acid (18:1) and linoleic acid (18:2) than with stearic acid (18:0) and had both a higher kcat and a higher Km for linoleic than oleic acid in the presence of 8 mM 4NPGlc donor. Os9BGlu31 knockout mutant rice lines were found to have significantly larger amounts of fatty acid glucose esters than wild-type control lines. Because the transglucosylation reaction is reversible, these data suggest that fatty acid glucose esters act as glucosyl donor substrates for Os9BGlu31 transglucosidase in rice.


Four new nematode species (Araeolaimida: Comesomatidae, Diplopeltidae) from the New Zealand continental slope.
Four new nematode species of the order Araeolaimida are described from the continental slope of New Zealand: Sabatieria megadena sp. n., Pararaeolaimus tetradenus sp. n., Southerniella parasimplex sp. n., and Diplopeltula cuspidiboja sp. n. The present study provides the first record of the genus Pararaeolaimus in the New Zealand Exclusive Economic Zone. Pararaeolaimus megaloamphidus Timm, 1961, Diplopeltula mollis Bussau, 1993 and Diplopeltula peruensis Bussau, 1993 are considered species inquirendae due to the incomplete nature of the original descriptions. Southerniella amblynema Bussau, 1993, Southerniella lympha Bussau, 1993, and Southerniella nojii Jensen, 1991 are transferred to the genus Intasia Tchesunov & Miljutina, 2008 due to the presence of a single anterior outsretched ovary. A key to valid Southerniella species is provided.


Hip segmentation from MRI volumes in infants for DDH diagnosis and treatment planning.
Diagnosis and surgical management of Developmental Dysplasia of the Hip (DDH) relies on physical examination and 2D ultrasound scanning. Magnetic Resonance Imaging (MRI) can be used to complement existing techniques and could be advantageous in treatment planning due to its larger field of view. In this paper we propose a semi-automatic method to segment surface models of the acetabulum from MRI images. The method incorporates clinical knowledge in the form of intensity priors which are integrated into a Random Walker (RW) formulation. We use a modified RW framework which compensates for incomplete or blurred boundaries in the image by using information from neighboring slices in the sequence incorporated as node weights. We conducted a pilot study to evaluate the segmentation on a set of 10 infant hip MRI sequences using a 1.5 Tesla MR scanner. Contours obtained from the semi-automated segmentation were compared against manually segmented hip contours using Dice Ratio (DR), Hausdorff Distance (HD) and Root Mean Square (RMS) distance. The proposed method gave values of (DR = 0.84 ± 0.5, HD =3.0 ± 0.7, RMS =1.9 ± 0.3) and (DR=0.86 ± 0.2, HD=3.0 ± 0.1, RMS= 2.0 ± 0.6) for right and left acetabular contours respectively which was higher than the corresponding values obtained from conventional RW segmentation. The execution time of the segmentation algorithm was less than ~4 seconds on a 3.5 GHz CPU.


[Characterization of the change in DOM during wastewater chlorine and chlorine dioxide disinfections by 3DEEM].
The change of DOM (dissolve organic matter) during wastewater chlorine and chlorine dioxide disinfections was characterized by 3DEEM (three-dimensional excitation emission matrix fluorescence spectroscopy) method. The results showed that the DOM in wastewater tested was quite different from drinking water and surface waters. It contained more aromatic proteins and soluble microbial products, and the humus were predominately microbially derived and had less aromatic moieties. After chlorine and chlorine dioxide disinfections, the excitation or emission wavelength of EEM (excitation emission matrix) peaks for aromatic proteins and soluble microbial products shifted to longer wavelength by several nanometers, which was probably caused by the decomposition of aromatic structure; while the excitation or emission wavelength of EEM peaks for humus shifted to shorter wavelength by several to more than twenty nanometers, which was different from surface waters, and this phenomenon was considered to be caused by their different resources. Similar to the change in genotoxicity, ammonia nitrogen significantly influenced the change in EEM during chlorine disinfection, but not during chlorine dioxide disinfection.


Analyses of reaction norms reveal new chromosome regions associated with tick resistance in cattle.
Despite single nucleotide polymorphism (SNP) availability and frequent cost reduction has allowed genome-wide association studies even in complex traits as tick resistance, the use of this information source in SNP by environment interaction context is unknown for many economically important traits in cattle. We aimed at identifying putative genomic regions explaining differences in tick resistance in Hereford and Braford cattle under SNP by environment point of view as well as to identify candidate genes derived from outliers/significant markers. The environment was defined as contemporary group means of tick counts, since they seemed to be the most appropriate entities to describe the environmental gradient in beef cattle. A total of 4363 animals having tick counts (n=10 673) originated from 197 sires and 3966 dams were used. Genotypes were acquired on 3591 of these cattle. From top 1% SNPs (410) having the greatest effects in each environment, 75 were consistently relevant in all environments, which indicated SNP by environment interaction. The outliers/significant SNPs were mapped on chromosomes 1, 2, 5, 6, 7, 9, 11, 13, 14, 15, 16, 18, 21, 23, 24, 26 and 28, and potential candidate genes were detected across environments. The presence of SNP by environment interaction for tick resistance indicates that genetic expression of resistance depends upon tick burden. Markers with major portion of genetic variance explained across environments appeared to be close to genes with different direct or indirect functions related to immune system, inflammatory process and mechanisms of tissue destruction/repair, such as energy metabolism and cell differentiation.


Selective loss and axonal sprouting of GABAergic interneurons in the sclerotic hippocampus induced by LiCl-pilocarpine.
In this study, we performed immunohistochemistry for somatostatin (SS), neuropeptide Y (NPY), and parvalbumin (PV) in LiCl-pilocarpine-treated rats to observe quantitative changes and axonal sprouting of GABAergic interneurons in the hippocampus, especially in the sclerotic hippocampus. Fluoro-Jade B (FJB) was performed to detect the specific degeneration of GABAergic interneurons. Compared with age-matched control rats, there were fewer SS/NPY/PV-immunoreactive (IR) interneurons in the hilus of the sclerotic hippocampus in pilocarpine-treated rats; hilar dentritic inhibitory interneurons were most vulnerable. FJB stain revealed degeneration was evident at 2 months after status epilepticus. Some SS-IR and NPY-IR interneurons were also stained for FJB, but there was no evidence of degeneration of PV-IR interneurons. Axonal sprouting of GABAergic interneurons was present in the hippocampus of epileptic rats, and a dramatic increase of SS-IR fibers was observed throughout all layers of CA1 region in the sclerotic hippocampus. These results confirm selective loss and degeneration of a specific subset of GABAergic interneurons in specific subfields of the hippocampus. Axonal sprouting of inhibitory GABAergic interneurons, especially numerous increase of SS-IR neutrophils within CA1 region of the sclerotic hippocampus, may constitute the aberrant inhibitory circum and play a significant role in the generation and compensation of temporal lobe epilepsy.


Prognostic role of Fuhrman grade and vascular endothelial growth factor in pT1a clear cell carcinoma in partial nephrectomy specimens.
Conventional renal cell carcinoma (RCC) is characterized by rich neovascularization and shows a fine vascular network around tumor cells. Nephron sparing surgery has been established as a method of choice or necessity for localized tumors. We investigated the importance of microvessel density (MVD), vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (Flk-1) immunohistochemical expression in a large series of small conventional clear cell renal carcinomas treated with partial nephrectomy and assessed the prognostic value of their expression in terms of patients survival at long-term followup. A total of 48 patients with a mean age +/- SD of 58.2 +/- 9.5 years who had conventional single RCC were considered. Median tumor diameter was 2.92 +/- 0.82 cm (range 1.3 to 5). Disease was grades 1 to 4 in 15, 29, 2 and 2 patients, respectively. Median followup was 92.9 months (range 17 to 186). Four patients (3.9%) had died of metastatic renal cancer at a median followup of 23.5 months, of whom 1 had a grade 2, 1 had a grade 3 and 2 had grade 4 RCC. Patients with MVD expression higher than the median (44.4 vessels per mm) did not show a significant difference in survival compared to patients with MVD expression lower than the median. Patients with VEGF expression higher than 25% in the histological specimen showed worse survival than patients with VEGF expression lower than 25%. Different Flk-1 expression did not determine a significant difference in survival. On univariate analysis of patient survival in relation to the different considered factors Fuhrman grading was the most important factor for survival. Our study shows that recurrence and death are possible even in patients with small renal tumors. MVD, VEGF and Flk-1 expression do not depend on tumor size in pT1a RCC. Therefore, to date Fuhrman grading appears to be the only factor predictive of survival even in small RCC. Thus, Fuhrman grading is predictive of mortality. While VEGF is not predictive of survival as a single parameter, based on its percent of expression (lower or higher than 25%) it can determine 2 groups that are different from the prognostic point of view.


Quillaja Saponin Characteristics and Functional Properties.
Consumer concerns about synthetically derived food additives have increased current research efforts to find naturally occurring alternatives. This review focuses on a group of natural surfactants, the Quillaja saponins, that can be extracted from the Quillaja saponaria Molina tree. Quillaja saponins are triterpenoid saponins comprising a hydrophobic quillaic acid backbone and hydrophilic sugar moieties. Commercially available Quillaja saponin products and their composition and properties are described, and the technofunctionality of Quillaja saponins in a variety of food, cosmetic, and pharmaceutical product applications is discussed. These applications make use of the biological and interfacial activities of Quillaja saponins and their ability to form and stabilize colloidal structures such as emulsions, foams, crystallized lipid particles, heteroaggregates, and micelles. Further emphasis is given to the complexation and functional properties of Quillaja saponins with other cosurfactants to create mixed surfactant systems, an approach that has the potential to facilitate new interfacial structures and novel functionalities.


Vitamin B complex blocks the dust fall PM2 .5 -induced acute lung injury through DNA methylation in rats.
This study aimed to explore whether vitamin B complex (folic acid, B6 , and B12 ) could avert DNA methylation changes associated with inflammation induced by acute PM2.5 exposure. Sprague-Dawley rats were administered by gavage with different concentrations of vitamin B complex once a day for 28 days, and then by intratracheal instillation with saline or PM2.5 once every 2 days for three times. Vitamin B continued to be taken during the PM2.5 exposure. Rats were sacrificed 24 h after the last exposure. The results showed that vitamin B complex could block the pathological changes and injury in lungs induced by PM2.5 . Meanwhile, vitamin B complex could prevent the abnormal DNA methylation of IL-4 and IFN-γ to antagonize the imbalance of IL-4/IFN-γ associated with inflammation. It was further found that vitamin B complex could regulate DNA methyltransferases (DNMTs) and increase the S-adenosylmethionine (SAM)/S-Adenosyl-L-homocysteine (SAH) ratio to reverse the hypomethylation of genomic DNA and the abnormal DNA methylation of IL-4 and IFN-γ. In conclusion, vitamin B complex has a protective effect on acute lung injury by attenuating abnormal DNA methylation induced by PM2.5 in rats. This study may provide a new insight into the physiological function of vitamin B to prevent the health effects induced by PM2.5 .


Evaluation and Forecasting Analysis of the Association of Conditional Cash Transfer With Child Mortality in Latin America, 2000-2030.
Latin America has implemented the world's largest and most consolidated conditional cash transfer (CCT) programs during the last 2 decades. As a consequence of the COVID-19 pandemic, poverty rates have markedly increased, and a large number of newly low-income individuals, especially children, have been left unprotected. To evaluate the association of CCT programs with child health in Latin American countries during the last 2 decades and forecast child mortality trends up to 2030 according to CCT alternative implementation options. This cohort study used a multicountry, longitudinal, ecological design with multivariable negative binomial regression models, which were adjusted for all relevant demographic, socioeconomic, and health care variables, integrating the retrospective impact evaluations from January 1, 2000, to December 31, 2019, with dynamic microsimulation models to forecast potential child mortality scenarios up to 2030. The study cohort included 4882 municipalities from Brazil, Ecuador, and Mexico with adequate quality of civil registration and vital statistics according to a validated multidimensional criterion. Data analysis was performed from September 2022 to February 2023. Conditional cash transfer coverage of the target (lowest-income) population categorized into 4 levels: low (0%-29.9%), intermediate (30.0%-69.9%), high (70.0%-99.9%), and consolidated (≥100%). The main outcomes were mortality rates for those younger than 5 years and hospitalization rates (per 1000 live births), overall and by poverty-related causes (diarrheal, malnutrition, tuberculosis, malaria, lower respiratory tract infections, and HIV/AIDS), and the mortality rates for those younger than 5 years by age groups, namely, neonatal (0-28 days), postneonatal (28 days to 1 year), infant (<1 year), and toddler (1-4 years). The retrospective analysis included 4882 municipalities. During the study period of January 1, 2000, to December 31, 2019, mortality in Brazil, Ecuador, and Mexico decreased by 7.8% in children and 6.5% in infants, and an increase in coverage of CCT programs of 76.8% was observed in these Latin American countries. Conditional cash transfer programs were associated with significant reductions of mortality rates in those younger than 5 years (rate ratio [RR], 0.76; 95% CI, 0.75-0.76), having prevented 738 919 (95% CI, 695 641-782 104) child deaths during this period. The association of highest coverage of CCT programs was stronger with poverty-related diseases, such as malnutrition (RR, 0.33; 95% CI, 0.31-0.35), diarrhea (RR, 0.41; 95% CI, 0.40-0.43), lower respiratory tract infections (RR, 0.66, 95% CI, 0.65-0.68), malaria (RR, 0.76; 95% CI, 0.63-0.93), tuberculosis (RR, 0.62; 95% CI, 0.48-0.79), and HIV/AIDS (RR, 0.32; 95% CI, 0.28-0.37). Several sensitivity and triangulation analyses confirmed the robustness of the results. Considering a scenario of moderate economic crisis, a mitigation strategy that will increase the coverage of CCTs to protect those newly in poverty could reduce the mortality rate for those younger than 5 years by up to 17% (RR, 0.83; 95% CI, 0.80-0.85) and prevent 153 601 (95% CI, 127 441-180 600) child deaths by 2030 in Brazil, Ecuador, and Mexico. The results of this cohort study suggest that the expansion of CCT programs could strongly reduce childhood hospitalization and mortality in Latin America and should be considered an effective strategy to mitigate the health impact of the current global economic crisis in low- and middle-income countries.


Socioeconomic Factors Associated with Readmission after Deceased Donor Renal Transplantation.
Early hospital readmissions after kidney transplantation pose a significant financial burden and hardship for patients and health-care institutions alike. We sought to identify the risk factors associated with increased likelihood of readmission after transplantation, and examined to determine whether patient socioeconomic demographics impacted the likelihood of perioperative readmissions. We evaluated all deceased donor renal transplants performed at our institution between August 2011 and December 2015. In a cohort of 325 transplant operations that met our inclusion criteria, 117 (36%) were readmitted to the hospital within 90 days of discharge. In univariable analyses, length of stay and pretransplant disabled status were associated with increased likelihood of readmission within 90 days of transplant. When placed into multivariable models, there was a suggestion association with length of stay and disability status. Kidney donor profile index, estimated posttransplant survival, employment, race, age, and payor status were not associated with readmission. In conclusion, the factors associated with posttransplant readmission are not necessarily influenced by socioeconomic factors in our study population. The data collected in this single center study indicate that the factors associated with increased rates of readmission are likely clinical in nature.


Diffusion of small particles in polymer films.
The motion of small probe molecules in a two-dimensional system containing frozen polymer chains was studied by means of Monte Carlo simulations. The model macromolecules were coarse-grained and restricted to vertices of a triangular lattice. The cooperative motion algorithm was used to generate representative configurations of macromolecular systems of different polymer concentrations. The remaining unoccupied lattice sites of the system were filled with small molecules. The structure of the polymer film, especially near the percolation threshold, was determined. The dynamic lattice liquid algorithm was then employed for studies of the dynamics of small objects in the polymer matrix. The influence of chain length and polymer concentration on the mobility and the character of motion of small molecules were studied. Short- and long-time dynamic behaviors of solvent molecules were also described. Conditions of anomalous diffusions' appearance in such systems are discussed. The influence of the structure of the matrix of obstacles on the molecular transport was discussed.


Protection of CTGF Antibody Against Diabetic Nephropathy in Mice Via Reducing Glomerular β-Catenin Expression and Podocyte Epithelial-Mesenchymal Transition.
Despite substantial progress in medical care, the morbidity rate of diabetic nephropathy (DN) remains high in patients with diabetes. Evidence suggests that connective tissue growth factor (CTGF) induced podocyte injury may contribute to DN and CTGF inhibition could reduce albuminuria. However, to date the mechanisms involved in the effect of CTGF on podocyte injury have not been fully understood. The aim of this study is to investigate the effects of therapeutic CTGF antibody on glomerular β-catenin expression and podocyte epithelial-mesenchymal transition (EMT) in diabetic mice. C57BL/6J mice were randomly divided into three groups as the following: the control, DN, and DN treated by CTGF antibody group. DN was induced by a single intraperitoneal injection of streptozotocin and then CTGF antibody was administrated three times per week for 8 weeks. Urinary albumin excretion, mesangial proliferation and matrix deposition, and β-catenin expression in glomeruli at mRNA and protein level were all increased in DN mice compared to that in the control. Besides, the development of EMT in podocytes from diabetic mice, demonstrated by the downregulation of nephrin and upregulation of desmin in glomeruli, was detected. Furthermore, blocking CTGF by specific antibody reduced albuminuria, prevented the overexpression of CTGF, as well as β-catenin, in glomeruli and subsequently ameliorated podocyte EMT in DN mice. In summary, this study suggested that CTGF antibody protected podocytes against injury in DN mice by reducing β-catenin overexpression and preventing podocyte EMT, which might provide new insight into the mechanism of CTGF inhibition in the treatment of DN. J. Cell. Biochem. 118: 3706-3712, 2017. © 2017 Wiley Periodicals, Inc.


Role of monocarboxylate transport in the regulation of intracellular pH of renal proximal tubule cells.
Traditional models of acid-base transport and intracellular pH (pHi) regulation in the renal proximal tubule have been based on the existence of a Na+/H+ exchanger at the luminal membrane and a simple HCO3- conductance at the basolateral membrane. Our recent work, in which we used pH-sensitive microelectrodes or dyes to monitor pHi in isolated renal tubules perfused in the nominal absence of HCO3-, has demonstrated the existence of a novel mechanism of acid extrusion in amphibian and mammalian proximal tubule cells. The salamander proximal tubule, for example, possesses an electroneutral Na+ monocarboxylate (Na+-X-) co-transporter, but only at the luminal membrane. It also possesses an electroneutral H+-X- co-transporter, but only at the blood side or basolateral membrane. In the presence of lactate, the luminal Na+-lactate co-transporter mediates a net influx of lactate, driven by the Na+ gradient. The cell-to-blood lactate gradient, in turn, drives the coupled efflux of H+ and lactate across the basolateral membrane. The net effect is the reabsorption of lactate, the luminal uptake of Na+ and the basolateral extrusion of H+. Acid extrusion mediated by this monocarboxylate system in the salamander is comparable in magnitude to that mediated by the Na+/H+ exchanger. In the S3 segment of the rabbit proximal tubule, a similar monocarboxylate system (studied with acetate instead of lactate) extrudes acetate at twice the rate of the Na+/H+ exchanger. Thus, monocarboxylate transport, at least in the nominal absence of HCO3-, can have a major impact on pHi regulation.


The VASP-Spred-Sprouty domain puzzle.
Sprouty-related proteins with an EVH1 domain (Spreds) belong to a new protein family harboring a conserved N-terminal EVH1 domain, which is related to the VASP (vasodilator-stimulated phosphoprotein) EVH1 domain (Enabled/VASP homology 1 domain) and a C-terminal Sprouty-related domain, typical for Sprouty proteins. Spreds were, like Sproutys, initially discovered as inhibitors of the Ras/MAPK pathway, and the SPR (Sprouty-related) domains of both protein families seem to be very important for many protein interactions and cellular processes. VASP was initially characterized as a proline-rich substrate of protein kinases A and G in human platelets and later shown to be a scaffold protein, regulating both signal transduction pathways and the actin filament system. The VASP-EVH1 domain is known to bind specifically to a FP(4) binding motif, which is, for example, present in the focal adhesion proteins vinculin and zyxin. In this review we give a structural and functional overview on these three protein families and ask whether nature plays a modular protein domain puzzle with stable exchangeable elements or if these closely related domains have various functions when pasted in a different protein context.


Oxalate modulates thiobarbituric acid reactive species (TBARS) production in supernatants of homogenates from rat brain, liver and kidney: effect of diphenyl diselenide and diphenyl ditelluride.
The aim of this paper was to investigate the mechanism(s) involved in the sodium oxalate pro-oxidative activity in vitro and the potential protection by diphenyl diselenide ((PhSe)(2)) and diphenyl ditelluride ((PhTe)(2)) using supernatants of homogenates from brain, liver and kidney. Oxalate causes a significant increase in the TBARS (thiobarbituric acid reactive species) production up to 4mmol/l and it had antioxidant activity from 8 to 16mmol/l in the brain and liver. Oxalate had no effect in kidney homogenates. The difference among tissues may be related to the formation of insoluble crystal of oxalate in kidney, but not in liver and brain homogenates. (PhSe)(2) and (PhTe)(2) reduced both basal and oxalate-induced TBARS in rat brain homogenates, whereas in liver homogenates they were antioxidant only on oxalate-induced TBARS production. (PhSe)(2) showed a modest effect on renal TBARS production, whereas (PhTe)(2) did not modulate TBARS in kidney preparations. Oxalate at 2mmol/l did not change deoxyribose degradation induced by Fe(2+) plus H(2)O(2), whereas at 20mmol/l it significantly prevents its degradation. Oxalate (up to 4mmol/l) did not alter iron (10micromol/l)-induced TBARS production in the brain preparations, whereas at 8mmol/l onwards it prevents iron effect. In liver preparations, oxalate amplifies iron pro-oxidant activity up to 4mmol/l, preventing iron-induced TBARS production at 16mmol/l onwards. These results support the antioxidant effect of organochalcogens against oxalate-induced TBARS production. In addition, our results suggest that oxalate pro- and antioxidant activity in vitro could be related to its interactions with iron ions.


Nutrition markers in patients after heart surgery.
Nutrition support is an important aspect of multidisciplinary approaches in cardiology rehabilitation. However, little is known about the impact of a patient's nutrition status on recovery after elective heart surgery. The authors assessed changes in nutrition markers in patients undergoing postsurgical rehabilitation, and tested their correlation with systemic inflammatory responses and clinical outcomes to determine the adequacy of the prescribed dietary regimen. Plasma concentrations of nutrition biomarkers were measured in 50 nondiabetic patients upon admission to a cardiology rehabilitation unit after coronary artery bypass grafting or mitral and/or aortic valve replacement (D0), and again 16 days later (D16). On D16, low plasma albumin increased, anemia improved, and high levels of inflammation markers declined. Vitamins remained stable within normal values, with the exception of vitamin B12, which decreased significantly from 516 +/- 341 to 445 +/- 212 ng/mL (P = .007). Blood glucose was >110 mg/dL in 51% of the patients at baseline; this proportion did not decline after rehabilitation. Overweight patients (body mass index >25 kg/m(2)) were prevalent (58%). They showed a slightly but not significantly greater inflammatory response and had a higher incidence of infective complications than the normal-weight group, but similar levels of nutrition markers. The standard dietary regimen followed during cardiological rehabilitation after major cardiovascular surgery aids recovery from surgical insult, but fails to normalize high glucose levels. Vitamin B12 supplementation should be encouraged because of its substantial reduction during the rehabilitation period.


Interaction of electrons with light metal hydrides in the transmission electron microscope.
Transmission electron microscope (TEM) observation of light metal hydrides is complicated by the instability of these materials under electron irradiation. In this study, the electron kinetic energy dependences of the interactions of incident electrons with lithium, sodium and magnesium hydrides, as well as the constituting element effect on the interactions, were theoretically discussed, and electron irradiation damage to these hydrides was examined using in situ TEM. The results indicate that high incident electron kinetic energy helps alleviate the irradiation damage resulting from inelastic or elastic scattering of the incident electrons in the TEM. Therefore, observations and characterizations of these materials would benefit from increased, instead decreased, TEM operating voltage.


Comparisons of achievement, effort, and self-perceptions among students with learning disabilities and their peers from different achievement groups.
This study compared the social-emotional implications of academic achievement for students with and without learning disabilities (LD) and identified predictors of effort investment. Students with LD showed lower levels of achievement, effort investment, academic self-efficacy, sense of coherence, positive mood, and hope, and higher levels of loneliness and negative mood. When compared to peers without LD (n = 447) at four different academic achievement levels, students with LD showed higher achievement than the low-average group, but their social-emotional profiles were similar to the low and low-average groups. Hierarchical multiple regression analysis showed that achievement, academic self-efficacy, negative mood, and hope predicted effort investment for students with LD. These results demonstrated the importance of hope in understanding the functioning of students with LD.


A novel mutation, Arg71Thr, in the delta-sarcoglycan gene is associated with dilated cardiomyopathy.
Approximately 20-35% of cases of idiopathic dilated cardiomyopathy are familial. DCM-associated mutations have been reported in 13 genes including the desmin, delta-sarcoglycan, and metavinculin genes. This study screened for variants in these genes in Finnish patients with DCM. All coding regions of the desmin and delta-sarcoglycan genes and the metavinculin-specific exon of the vinculin gene were screened in 52 DCM patients from eastern Finland by PCR-SSCP. We detected a novel mutation, Arg71Thr, in the delta-sarcoglycan gene in two members of a small DCM family. One of the mutation carriers fulfills diagnostic criteria for DCM and is also symptomatic. The other mutation carrier has slightly dilated left ventricle and well preserved systolic function. Therefore carriers of the Arg71Thr mutation had a relatively mild phenotype and a late onset of the disease. Disease-associated mutations were not found in the desmin gene or the metavinculin-specific exon of the vinculin gene. We conclude that the desmin and delta-sarcoglycan genes are not predominant disease-causing genes in patients with DCM in eastern Finland.


Microfluidic Platform for the Long-Term On-Chip Cultivation of Mammalian Cells for Lab-On-A-Chip Applications.
Lab-on-a-Chip (LoC) applications for the long-term analysis of mammalian cells are still very rare due to the lack of convenient cell cultivation devices. The difficulties are the integration of suitable supply structures, the need of expensive equipment like an incubator and sophisticated pumps as well as the choice of material. The presented device is made out of hard, but non-cytotoxic materials (silicon and glass) and contains two vertical arranged membranes out of hydrogel. The porous membranes are used to separate the culture chamber from two supply channels for gases and nutrients. The cells are fed continuously by diffusion through the membranes without the need of an incubator and low requirements on the supply of medium to the assembly. The diffusion of oxygen is modelled in order to find the optimal dimensions of the chamber. The chip is connected via 3D-printed holders to the macroscopic world. The holders are coated with Parlyene C to ensure that only biocompatible materials are in contact with the culture medium. The experiments with MDCK-cells show the successful seeding inside the chip, culturing and passaging. Consequently, the presented platform is a step towards Lab-on-a-Chip applications that require long-term cultivation of mammalian cells.


[Role of outpatient psychiatry in therapy of patients with eating disorder].
Eating disorders are common illness but the proportion of those in treatment is still low and their liability to abandon treatment is a constant danger. This is largely due to the pathology: in particular splitting and denial. Thus, the integration of various types of treatment is essential and the process of integration will be efficiently managed if a psychiatric clinic works as a center of the therapeutic network. Formerly, long-term in-patient treatment was regarded as the best choice for treating the patient thoroughly. Nowadays such treatment is not recommended due to the large cost involved in such treatment. Also, removing the patient from a community environment and confining them to an institution over a long period is now regarded as discouraging independence. Thus, the focus of treatment has shifted from in-patient to out-patient treatment. A new model for multi-disciplinary work is now needed because sharing patient information between professionals is more difficult at the outpatient clinic than on an in-patient ward with shared case notes. In order to make the treatment network functional, patients themselves are expected to possess a clear understanding of the illness and its treatment. The application of motivational enhancement theory is useful in this respect. It is the responsibility of psychiatric clinics to encourage the continuous improvement of patient motivation for treatment and to make patients tolerant towards changes in treatment settings.


Questions regarding the safety and duration of immunity following live yellow fever vaccination.
The World Health Organization (WHO) and other health agencies have concluded that yellow fever booster vaccination is unnecessary since a single dose of vaccine confers lifelong immunity. Areas covered: We reviewed the clinical studies cited by health authorities in their investigation of both the safety profile and duration of immunity for the YFV-17D vaccine and examined the position that booster vaccination is no longer needed. We found that antiviral immunity may be lost in 1-in-3 to 1-in-5 individuals within 5 to 10 years after a single vaccination and that children may be at greater risk for primary vaccine failure. The safety profile of YFV-17D was compared to other licensed vaccines including oral polio vaccine (OPV) and the rotavirus vaccine, RotaShield, which have subsequently been withdrawn from the US and world market, respectively. Expert commentary: Based on these results and recent epidemiological data on vaccine failures (particularly evident at >10 years after vaccination), we believe that current recommendations to no longer administer YFV-17D booster vaccination be carefully re-evaluated, and that further development of safer vaccine approaches should be considered.


Potential influence of κ-casein and β-lactoglobulin genes in genetic association studies of milk quality traits.
From a review of published information on genetic association studies, a meta-analysis was conducted to determine the influence of the genes κ-casein (CSN3) and β-lactoglobulin (LGB) on milk yield traits in Holstein, Jersey, Brown Swiss, and Fleckvieh. The GLIMMIX procedure was used to analyze milk production and percentage of protein and fat in milk. Models included the main effects and all their possible two-way interactions; not estimable effects and non-significant (p>0.05) two-way interactions were dropped from the models. The three traits analyzed used Poisson distribution and a log link function and were determined with the Interactive Data Analysis of SAS software. Least square means and multiple mean comparisons were obtained and performed for significant main effects and their interactions (p<0.0255). Interaction of breed by gene showed that Holstein and Fleckvieh were the breeds on which CSN3 (6.01%±0.19% and 5.98%±0.22%), and LGB (6.02%±0.19% and 5.70%±0.22%) have the greatest influence. Interaction of breed by genotype nested in the analyzed gene indicated that Holstein and Jersey showed greater influence of the CSN3 AA genotype, 6.04%±0.22% and 5.59%±0.31% than the other genotypes, while LGB AA genotype had the largest influence on the traits analyzed, 6.05%±0.20% and 5.60%±0.19%, respectively. Furthermore, interaction of type of statistical model by genotype nested in the analyzed gene indicated that CSN3 and LGB genes had similar behavior, maintaining a difference of more than 7% across analyzed genotypes. These results could indicate that both Holstein and Jersey have had lower substitution allele effect in selection programs that include CSN3 and LGB genes than Brown Swiss and Fleckvieh. Breed determined which genotypes had the greatest association with analyzed traits. The mixed model based in Bayesian or Ridge Regression was the best alternative to analyze CSN3 and LGB gene effects on milk yield and protein and fat percentages.


Development of new methodologies for the mass spectrometry study of bioorganic macromolecules.
In recent years, mass spectrometry has been increasingly used for the analysis of various macromolecules of biological, biomedical, and biochemical interest. This increase has been made possible by two key developments: the advent of electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI) sources. The two new techniques produce a significant increase in mass range and in sensitivity that led to the development of new applications and of new analyzer designs, software, and robotics. This review, apart from the description of the status of mass spectrometry in the analysis of bioorganic macromolecules, is mainly devoted to the illustration of the more recent promising techniques and on their possible future evolution.


Highland barley β-glucan alleviated western diet-induced non-alcoholic fatty liver disease via increasing energy expenditure and regulating bile acid metabolism in mice.
Non-alcoholic fatty liver disease (NAFLD) has become a public health burden. Controlling bile acids (BAs) metabolism and energy expenditure are potential therapies for NAFLD. Because one of the main health effects of cereal β-glucan (BG) is its ability to lower cholesterol by interacting with BAs, BG may regulate imbalances of the metabolism of BAs during NAFLD. Therefore, by using metabolic tests coupled with the profiling of hepatic BAs, we have assessed the effect of BG from highland barley on western diet (WD) induced NAFLD mice. BG treatment prevented fat accumulation and increased adipose lipolysis. These moderating effects were associated with an increased energy expenditure. Moreover, BG-treated mice enhanced the production of hepatic BAs, which may be connected with the activation of farnesoid X receptor (FXR) signaling in the liver and inhibition of FXR signaling in the ileum. Our results suggest that BG prevents fat accumulation by increasing energy expenditure, a mechanism associated with major changes in the composition of hepatic BAs.


Managing during times of uncertainty. Part I--Short-term strategies.
During times of uncertainty, nurse managers must first and foremost act like leaders. They must be visible, stay focused on the situation at hand, demonstrate congruency, convey empathy to their employees, and communicate effectively. While this discussion has dealt with some "short term" approaches to handle uncertain situations, short term may be hours, days, or weeks depending on the type of crisis or situation. The strategies are critical to managing situations during the period immediately following an unexpected event. However, these strategies do not become obsolete as managers begin to address the long term ramifications of the event. Rather, they should serve as a foundation and guide for future management activity.


[Obstructive sleep apnea contribution to oxidative stress in obesity].
The aim of this paper was to check the influence of obstructive sleep apnea (OSA) on obesity oxidative stress and CPAP (Continuous Positive Airway Pressure) effect on oxidative stress and in these patients. Twenty nine male patients considered obese (BMI > 30 kg/m(2)) were divided into 3 groups: a) Group I: 10 OSA free patients (apnea-hipopnea index (AHI) < 5); b) Group 2: 10 with moderate to serious OSA (AHI > 20); c) Group 3: 9 with OSA from moderate to serious (AHI > 20) using CPAP, minimum 4 hours/night for 2 months. Significant differences before and after CPAP usage were observed in group 3 in the following variables: reduction of superoxide (SO) production [13.2 (10.3-19.6) vs. 10.5 (5.8-11.8) nmoles O2(-)/2 x 10(6) PMN] and increase in serum nitrite/nitrates levels [24.5 (16.7-33.5) vs. 49.5 (39.3-58.1) microM]. Positive correlation between Apnea-Hypopnea Index (AHI) and SO (r = 0,726) and negative correlation was observed between AHI and serum nitrite/nitrates levels (r = - 0.867). In conclusion, oxidative stress present in obesity is elevated by OSA and CPAP treatment can rise the levels of SO and can decrease serum nitrite/nitrates present in obese patients with OSA.


Comparison of vincristine and vindesine in the treatment of inoperable non-small cell bronchial carcinoma.
Sixty-three patients with inoperable symptomatic non-small cell carcinoma of the bronchus were randomly allocated to receive either vincristine (1.4 mg/m2) or vindesine (3 mg/m2). These drugs were given weekly for four doses, then every 2 weeks for two further doses, and then continued monthly if there had been a response. Only five partial responses (greater than 50% reduction) were obtained with vindesine and none with vincristine. Disabling toxic effects occurred in 13 patients. This was more common with vindesine, but this group also received more prolonged therapy. Vindesine has modest activity against non-small cell carcinoma of the bronchus and may be more effective than vincristine, with similar toxicity.


The role of regulatory T cells in the pathogenesis of acute kidney injury.
The incidence of acute kidney injury (AKI) is on the rise and is associated with high mortality; however, there are currently few effective treatments. Moreover, the relationship between Tregs and other components of the immune microenvironment (IME) in the pathogenesis of AKI remains unclear. We downloaded four publicly accessible AKI datasets, GSE61739, GSE67401, GSE19130, GSE81741, GSE19288 and GSE106993 from the gene expression omnibus (GEO) database. Additionally, we gathered two kidney single-cell sequencing (scRNA-seq) samples from the Department of Organ Transplantation at Zhujiang Hospital of Southern Medical University to investigate chronic kidney transplant rejection (CKTR). Moreover, we also collected three samples of normal kidney tissue from GSE131685. By analysing the differences in immune cells between the AKI and Non-AKI groups, we discovered that the Non-AKI group contained a significantly greater number of Tregs than the AKI group. Additionally, the activation of signalling pathways, such as inflammatory molecules secretion, immune response, glycolytic metabolism, NOTCH, FGF, NF-κB and TLR4, was significantly greater in the AKI group than in the Non-AKI group. Additionally, analysis of single-cell sequencing data revealed that Tregs in patients with chronic kidney rejection and in normal kidney tissue have distinct biology, including immune activation, cytokine production, and activation fractions of signalling pathways such as NOTCH and TLR4. In this study, we found significant differences in the IME between AKI and Non-AKI, including differences in Tregs cells and activation levels of biologically significant signalling pathways. Tregs were associated with lower activity of signalling pathways such as inflammatory response, inflammatory molecule secretion, immune activation, glycolysis.


The reimbursement coverage decisions and pricing rules for medical devices in Taiwan.
Medical technology is undergoing rapid transformations, and the classifications of medical devices have also expanded greatly; therefore, it is necessary to develop appropriate reimbursement policies and pricing mechanisms in a timely manner. This paper aims to introduce the reimbursement coverage and pricing rules for medical devices in Taiwan. In addition, this paper identifies and evaluates available health technology assessments (HTA) and literature on published websites concerning medical device decision-making processes and pricing systems in South Korea and Japan, which are near Taiwan and have similar reimbursement coverage processes. Reimbursement policy and pricing mechanisms are constantly being revised in Taiwan, Japan, and South Korea. Recently, all three countries attempted to establish new reimbursement coverage decision-making and pricing rules, adopting a differentiated approach based on the level of evidence required for the appropriated reimbursement in terms of a feasible evaluation mechanism for providing patients with more effective medical devices. This article is expected to contribute to providing references to new reimbursement coverage decision-making and pricing rules.


The dynamics of lead in drinking water in U.S. workplaces and schools.
A statistical analysis of water samples from over 12,000 school and workplace water coolers, bubblers, chillers, faucets, and ice makers determined that there is a substantial risk of excessive lead concentrations in first-draw water from sources of all types. Of all sources tested, 17.2% had lead concentrations in excess of 15 ppb. A comparison of lead concentrations by brand of water cooler was made for all manufacturers for which at least 50 samples were available. The percentage of water sources with first-draw lead concentrations above 15 ppb was reduced by 58%-84% by flushing the source prior to use. Special attention was given to determining the relationships between lead levels and factors such as water pH, water cooler age, and line purging. While each of these variables was found to be statistically significant, the overwhelming indication of this research is that testing individual water sources is apparently the only reliable way to determine whether a lead contamination problem exists.


Trends Among Rural and Urban Medicare Beneficiaries in Care Delivery and Outcomes for Acute Stroke and Transient Ischemic Attacks, 2008-2017.
Over the last decade or so, there have been substantial investments in the development of stroke systems of care to improve access and quality of care in rural communities. Whether these have narrowed rural-urban disparities in care is unclear. To describe trends among rural and urban patients with acute ischemic stroke or transient ischemic attack in the type of health care centers to which patients were admitted, what care was provided, and the outcomes patients experienced. This descriptive observational study included 100% claims for beneficiaries of traditional fee-for-service Medicare from 2008 through 2017. All rural and urban areas in the US were included, defined by whether a beneficiary's residential zip code was in a metropolitan or nonmetropolitan area. All admissions in the US among patients with traditional Medicare who had a transient ischemic attack or acute stroke (N = 4.01 million) were eligible to be included in this study. Admissions for beneficiaries with end-stage kidney disease (n = 85 927 [2.14%]), beneficiaries with unidentified Rural-Urban Commuting Area codes (n = 12 797 [0.32%]), and beneficiaries not continuously enrolled in traditional Medicare in the 12 months before and 3 months after their admission (n = 442 963 [11.0%]) were excluded. Residence in an urban or rural area; admission to a hospital with a transient ischemic attack or acute stroke. Discharge from a certified stroke center, receiving a neurology consultation during admission, treatment with alteplase, days institutionalized, and 90-day mortality. The final sample included 3.47 million admissions from 2008 through 2017. In this sample, 2.01 million patients (58.0%) were female, and the mean (SD) age was 78.6 (10.5) years. In 2008, 24 681 patients (25.2%) and 161 217 patients (60.6%) in rural and urban areas, respectively, were cared for at a certified stroke center (disparity, -35.4%). By 2017, this disparity was -26.6%, having narrowed by 8.7 percentage points (95% CI, 6.6-10.8 percentage points). There was also narrowing in the rural-urban disparity in neurologist evaluation during admission (6.3% [95% CI, 4.2%-8.4%]). However, the rural-urban disparity widened or was similar with regard to receiving alteplase (0.5% [95% CI, 0.1%-0.8%]), mean days in an institution from admission (0.5 [95% CI, 0.2-0.8] days), and mortality at 90 days (0.3% [95% CI, -0.02% to 0.6%]), respectively. In the last decade, care for rural residents with acute ischemic stroke and transient ischemic attack has shifted to certified stroke centers and now more likely includes neurologist input. However, disparities in access to treatments, such as alteplase, and outcomes persist, highlighting that work still is needed to extend improvements in stroke care to all US residents.


The phases-of-treatment model for methadone maintenance: implementation and evaluation.
The phases-of-treatment model for methadone maintenance provides a clinical framework for the use of methadone to effectively meet the needs of individual patients. The therapeutic process is highly structured and is divided into several phases of treatment for opioid addiction. The first three phases--Intensive Stabilization, Commitment, and Rehabilitation--provide intensive services and are designed to stabilize patients and allow them to attain an optimal level of productive functioning. Then, in consultation with the treatment team, patients select one of two tracks, the Medical Maintenance phase or the Tapering phase, followed by the Reinforcement phase. This article provides an overview of the phases-of-treatment model and discusses procedures for its implementation. Also discussed are staffing patterns and staff training issues, as well as the use of performance-based standards for program evaluation and quality improvement within the context of the phases model.


Occurrence of malignancies in Hungarian patients with systemic lupus erythematosus: results from a single center.
As a result of increasing life expectancy of lupus patients, malignant disorders have become major determinants of morbidity and mortality. The objectives of this study were to analyze cancer-associated morbidity and mortality, the type of malignancies in Hungarian lupus patients, and to analyze association with immune-suppressive therapy, disease duration, and age of the patients. Data from 860 systemic lupus erythematosus (SLE) patients were retrospectively analyzed in a study period between 1970 and 2004. Results were compared to data from age- and sex-matched population obtained from the Health for All database, and also to literature data. A total of 37 patients presented with cancer, reflecting 4.3% cancer-associated morbidity. Patients were 47 (20-73) years old at the onset of malignancy, which appeared 13 (1-45) years later than SLE. Cancer prevalence was the highest in the first 5-10 years of lupus. Breast cancer was the most common malignancy (n = 11) followed by gastrointestinal tumors (n = 9), cervix cancer and hematologic malignancies (n = 5 for both), bronchial cancer (n = 4), bladder, skin, and ovarian cancer (n = 1 for each). Standardized incidence ratio was the highest for non-Hodgkin lymphoma (standardized incidence ratio [SIR] 3.5, 95% CI 0.4-12.5) and cervix cancer (SIR 1.7, 95% CI 0.6-4.1). Although 76% of patients with cancer received immune-suppressive therapy besides corticosteroids, no direct correlation could be confirmed between therapy and malignancy. Out of the 164 patients that expired during the study period, 18 were cancer-related. As such the cancer-associated mortality was 11% (18/164). This peaked during the last 4 years of the study period (8/24, 33%). Lupus patients are at high risk for particular types of malignant disorders, highlighting the importance of screening measures and focused patient examination.


Oral immunisation and its significance in the prophylactic control of enteritis in the preruminant calf.
Oral immunisation using a feed-incorporated vaccine comprising heat inactivated Escherichia coli and Salmonellae antigens was examined in feeding trials with calves. The studies were conducted with batches of calves purchased at intervals throughout one year and reared in an environment created by continuous occupancy. Improved health was registered in terms of a significant reduction in the incidence and duration of diarrhoea (P less than 0.01) and in the need for treatment with medicament or antibiotics (P less than 0.01). Orally immunised calves showed a significantly better weight gain (1.44 kg, P less than 0.05) than the controls during the period 0 to 5 weeks. This gain was mainly obtained during the first three weeks when the antigen fed calves showed significantly improved faeces scores and a significantly better appetite for concentrates (P less than 0.05).


The del22q11.2 candidate gene Tbx1 controls regional outflow tract identity and coronary artery patterning.
TBX1, encoding a T-box containing transcription factor, is the major candidate gene for del22q11.2 or DiGeorge syndrome, characterized by craniofacial and cardiovascular defects including tetralogy of Fallot and common arterial trunk. Mice lacking Tbx1 have severe defects in the development of pharyngeal derivatives including cardiac progenitor cells of the second heart field that contribute to the arterial pole of the heart. The outflow tract of Tbx1 mutant embryos is short and narrow resulting in common arterial trunk. Here we show by a series of genetic crosses using transgene markers of second heart field derived myocardium and coronary endothelial cells that a subdomain of myocardium normally observed at the base of the pulmonary trunk is reduced and malpositioned in Tbx1 mutant hearts. This defect is associated with anomalous coronary artery patterning. Both right and left coronary ostia form predominantly at the right/ventral sinus in mutant hearts, proximal coronary arteries coursing across the normally coronary free ventral region of the heart. We have identified Semaphorin3c as a Tbx1-dependent gene expressed in subpulmonary myocardium. Our results implicate second heart field development in coronary artery patterning and provide new insights into the association between conotruncal defects and coronary artery anomalies.


Transesophageal echocardiographic detection of atrial thrombi in patients with nonfibrillation atrial tachyarrhythmias and congenital heart disease.
We hypothesized an association between atrial thrombi and nonfibrillation atrial tachyarrhythmias in patients with congenital heart disease. We observed a fatal thromboembolus after direct current cardioversion in an adolescent with atrial flutter and repaired tetralogy of Fallot. Using transesophageal echocardiography, we prospectively studied 19 consecutive patients with congenital heart disease with nonfibrillation atrial tachyarrhythmia (atrial flutter in 18, primary atrial tachycardia in 1) undergoing electrophysiologic procedures (median age 19.6 years, range 7.0 to 53.8; 11 male, 8 female). Transthoracic echocardiograms were available for 17 patients. All transesophageal examinations were performed without incident. No atrial thrombi were detected in 11 patients who subsequently had uncomplicated direct current cardioversion. Eight solitary atrial thrombi were detected (incidence 42%). Six thrombi were located in the right atrium (Fontan repair in four patients, Ebstein's malformation repair in two), and two were noted in the left atrium (congenital hypertrophic cardiomyopathy and atrial septal defect repair in one patient each). Transthoracic echocardiograms were available in seven of eight patients with thrombus detected by transesophageal echocardiography, with only one study conclusive for an atrial thrombus. Cardioversion was deferred in six of eight patients with thrombus, and anticoagulation therapy was initiated. Uncomplicated electrophysiologic procedures were conducted in two patients at the time of detection of right atrial thrombus (atrioventricular node ablation in one patient, direct current cardioversion in the other). Prothrombin conditions exist in patients with congenital heart disease with nonfibrillation atrial tachyarrhythmias, as indicated by a significant incidence of transesophageally detected atrial thrombi. The need for prophylactic anticoagulation and the safety of pharmacologic or direct current cardioversion are issues that remain unresolved.


Effect of potassium channel noise on nerve discharge based on the Chay model.
The nervous system senses and transmits information through the firing behavior of neurons, and this process is affected by various noises. However, in the previous study of the influence of noise on nerve discharge, the channel of some noise effects is not clear, and the difference from other noises was not examined. To construct ion channel noise which is more biologically significant, and to clarify the basic characteristics of the random firing rhythm of neurons generated by different types of noise acting on ion channels. Based on the dynamics of the ion channel, we constructed ion channel noise. We simulated the nerve discharge based on the Chay model of potassium ion channel noise, and used the nonlinear time series analysis method to measure the certainty and randomness of nerve discharge. In the Chay model with potassium ion noise, the chaotic rhythm defined by the original model could be effectively unified with the random rhythm simulated by the previous random Chay model into a periodic bifurcation process. This method clarified the influence of ion channel noise on nerve discharge, better understood the randomness of nerve discharge and provided a more reasonable explanation for the mechanism of nerve discharge.


The occurrence of leg ulcers in Auckland: results of a population-based study.
To estimate the cumulative incidence rate and prevalence of leg ulcers in Auckland. A cross-sectional study was conducted to identify all individuals who had or developed a leg ulcer in the North Auckland and Central Auckland health districts between 1997 and 1998. Cases were identified through multiple sources, including community-based and hospital-based health professionals and by self-notification. All ulcer types were investigated. 611 individuals with healed or current leg ulcers were identified during the study period, of whom 426 had current leg ulcers. The annual cumulative incidence rate was 32 per 100,000. The point prevalence of current leg ulcers was 39 per 100,000, with a period prevalence of 79 per 100,000 per year. Men had lower age-adjusted incidence rates than women, but a higher age-adjusted point prevalence of leg ulceration, indicating that ulcers take longer to heal in men. Annual cumulative incidence rates increased steeply with age (< 60 years = 4, 60-69 years = 62, 70-79 years = 191, 80+ years = 466 per 100,000 per year), as did point prevalence (< 60 years = 5, 60-69 years = 76, 70-79 years = 238, 80+ years = 564 per 100,000). These data indicate that the risk of developing leg ulcers increases dramatically with age, with individuals aged 60 years and over particularly at risk. Given New Zealand's rapidly ageing population, the number of older people with leg ulcers each year is expected to double in the next 25 years.


The effectiveness and practicality of occupational stress management interventions: a survey of subject matter expert opinions.
Stress management (SM) subject matter experts (SMEs) evaluated 6 widely used occupational SM interventions (relaxation, physical fitness, cognitive restructuring, meditation, assertiveness training, and stress inoculation) on the basis of 10 practicality criteria and 7 effectiveness objectives. Relaxation was evaluated overall as the most practical intervention, while meditation and stress inoculation were judged as the least practical. Physical fitness was chosen to be the most effective intervention, while both meditation and assertiveness training were rated overall as the least effective. The findings also revealed that the SMEs considered history of success and duration of effect, rather than "relevance to program objectives," as the most important factors when selecting SM interventions. Incongruence between effectiveness ratings and actual choices of interventions are discussed.


The OH-stretching and OOH-bending overtone spectrum of HOONO.
We have simulated the HOONO vibrational overtone spectrum with use of a local mode Hamiltonian that includes the OH-stretching, OOH-bending, and NOOH-torsional modes and coupling between all three modes. The local mode parameters and the dipole moment function are calculated with coupled-cluster ab initio theory and an augmented Dunning-type triple-zeta basis set. We investigate the accuracy of the local mode parameters obtained from two different potential-energy fitting routines, as well as the sensitivity of these parameters to the basis set employed. We compare our simulated spectra to previously published action spectra in the first and second OH-stretching overtone regions. In addition we have recorded the spectrum in the OH-stretch and OOH-bend combination region around 7700 cm-1 and we also compare to this. Our simulated spectrum is in qualitative agreement with experiment in the first and second OH-stretching overtone and in the stretch-bend regions.


Prediction of diabetes mellitus after kidney transplantation using patient-specific induced pluripotent stem cells.
Multiple risk factors are involved in new-onset diabetes mellitus (DM) after organ transplantation; however, their ability to predict clinical prognosis remains unclear. Therefore, we investigated whether patient-specific induced pluripotent stem cells (iPSCs) could help predict DM development before performing kidney transplantation (KT). We first performed whole transcriptome and functional enrichment analyses of KT patient-derived iPSCs. Our results revealed that insulin resistance, type 2 DM, and transforming growth factor beta signaling pathways are associated between the groups of DM and non-DM. We next determined whether the genetic background was associated with development of iPSCs into pancreatic progenitor (PP) cells. The levels of differentiation-related key markers of PP cells were significantly lower in the DM group than in the non-DM group. Moreover, the results of tacrolimus toxicity screening showed a significant decrease in the number of PP cells of the DM group compared with the non-DM group, suggesting that these cells are more susceptible to tacrolimus toxicity. Taken together, these results indicate that PP cells of the DM group showed low developmental potency accompanied by a significantly different genetic background compared with the non-DM group. Thus, genetic analysis can be used to predict the risk of DM before KT.


A new type of square columnar liquid crystalline phases formed by facial amphiphilic triblock molecules.
A series of three novel liquid crystalline amphiphilic molecules is reported which are composed of three incompatible molecular parts, a rigid terphenyl core, two lipophilic decyloxy chains in the terminal 4- and 4' '-positions, and a polar group in the lateral 2'-position. The polar group comprises a polyether chain, an amide group, and a polyhydroxyalkyl end group (1-acylamino-1-deoxy-d-sorbitol derivatives). The self-organization of these compounds was studied by polarized light microscopy, differential scanning calorimetry, and different X-ray diffraction techniques. These investigations confirm a novel liquid crystalline phase with a square 2D-lattice (square columnar mesophase, plane group p4mm). This structure is built up by a set of three distinct columns, namely columns containing the polar lateral groups, columns incorporating the alkyl chains, and ribbons of the rodlike terphenyl units. The calamitic cores form walls bounding square-shaped channels occupied by the microsegregated polar lateral chains. The lipophilic columns containing alkyl chains are at the corners interconnecting the aromatic rods end-to-end.


Reduced Transcriptome Analysis of Zebrafish Embryos Prioritizes Environmental Compounds with Adverse Cardiovascular Activities.
Cardiovascular diseases are the leading cause of premature death in humans and remain a global public health challenge. While age, sex, family history, and false nutrition make a contribution, our understanding of compounds acting as cardiovascular disruptors is far from complete. Here, we aim to identify cardiovascular disruptors via a reduced transcriptome atlas (RTA) approach, which integrates large-scale transcriptome data sets of zebrafish and compiles a specific gene panel related to cardiovascular diseases. Among 767 gene expression profiles covering 81 environmental compounds, 11 priority compounds are identified with the greatest effects on the cardiovascular system at the transcriptional level. Among them, metals (AgNO3, Ag nanoparticles, arsenic) and pesticides/biocides (linuron, methylparaben, triclosan, and trimethylchlorotin) are identified with the most significant effects. Distinct transcriptional signatures are further identified by the percentage values, indicating that different physiological endpoints exist among prioritized compounds. In addition, cardiovascular dysregulations are experimentally confirmed for the prioritized compounds via alterations of cardiovascular physiology and lipid profiles of zebrafish. The accuracy rate of experimental verification reaches up to 62.9%. The web-based RTA analysis tool, Cardionet, for rapid cardiovascular disruptor discovery was further provided at http://www.envh.sjtu.edu.cn/cardionet.jsp. Our integrative approach yields an efficient platform to discover novel cardiovascular-disrupting chemicals in the environment.


Optimization of the standard genetic code according to three codon positions using an evolutionary algorithm.
Many biological systems are typically examined from the point of view of adaptation to certain conditions or requirements. One such system is the standard genetic code (SGC), which generally minimizes the cost of amino acid replacements resulting from mutations or mistranslations. However, no full consensus has been reached on the factors that caused the evolution of this feature. One of the hypotheses suggests that code optimality was directly selected as an advantage to preserve information about encoded proteins. An important feature that should be considered when studying the SGC is the different roles of the three codon positions. Therefore, we investigated the robustness of this code regarding the cost of amino acid replacements resulting from substitutions in these positions separately and the sum of these costs. We applied a modified evolutionary algorithm and included four models of the genetic code assuming various restrictions on its structure. The SGC was compared both with the codes that minimize the objective function and those that maximize it. This approach allowed us to place the SGC in the global space of possible codes, which is a more appropriate and unbiased comparison than that with randomly generated codes because they are characterized by relatively uniform amino acid assignments to codons. The SGC appeared to be well optimized at the global scale, but its individual positions were not fully optimized because there were codes that were optimized for only one codon position and simultaneously outperformed the SGC at the other positions. We also found that different code structures may lead to the same optimality and that random codes can show a tendency to minimize costs under some of the genetic code models. Our results suggest that the optimality of SGC could be a by-product of other processes.


IL1R2, CCR2, and CXCR4 May Form Heteroreceptor Complexes with NMDAR and D2R: Relevance for Schizophrenia.
The mild neuroinflammation hypothesis of schizophrenia was introduced by Bechter in 2001. It has been hypothesized that a hypofunction of glutamatergic signaling via N-methyl-D-aspartate receptors (NMDARs) and hyperactivation of dopamine D2 receptors play a role in schizophrenia. The triplet puzzle theory states that sets of triplet amino acid homologies guide two different receptors toward each other and contributes to the formation of a receptor heteromer. It is, therefore, proposed that putative NMDAR-C-C chemokine receptor type 2 (CCR2), NMDAR-C-X-C chemokine receptor type 4 (CXCR4), and NMDAR- interleukin 1 receptor type II (IL1R2) heteromers can be formed in the neuronal networks in mild neuroinflammation due to demonstration of Gly-Leu-Leu (GLL), Val-Ser-Thr (VST), and/or Ser-Val-Ser (SVS) amino acid homologies between these receptor protomers. This molecular process may underlie the ability to produce symptoms of schizophrenia in mild neuroinflammation. In this state, volume transmission (VT) is increased involving increased extracellular vesicle-mediated VT from microglia and astroglia. These vesicles may contain CCR2, CXCR4, and/or IL1R2 as well as their ligands and upon internalization by endocytic pathways into neurons can form heteroreceptor complexes with NMDAR in the plasma membrane with pathological allosteric receptor-receptor interactions involving increased internalization and reduced NMDAR signaling. The triplet puzzle theory also suggests the formation of putative D2R-CCR2, D2R-CXCR4, and D2R-IL1R2 heteromers in mild neuroinflammation in view of their demonstrated sets of Leu-Tyr-Ser (LYS), Leu-Pro-Phe (LPF), and/or Ser-Leu-Ala (SLA) triplet homologies. These D2R heteroreceptor complexes may also contribute to schizophrenia-like symptoms in mild neuroinflammation by enhancing D2R protomer function.


Protection of Tong-Sai-Mai Decoction against Apoptosis Induced by H2O2 in PC12 Cells: Mechanisms via Bcl-2-Mitochondria-ROS-INOS Pathway.
Tong-Sai-Mai decoction (TSM) is a Chinese materia medica polyherbal formulation that has been applied in treating brain ischemia for hundreds of years. Because it could repress the oxidative stress in in vivo studies, now we focus on the in vitro studies to investigate the mechanism by targeting the oxidative stress dependent signaling. The relation between the neurogenesis and the reactive oxygen species (ROS) production remains largely unexamined. PC12 cells are excitable cell types widely used as in vitro model for neuronal cells. Most marker genes that are related to neurotoxicity, apoptosis, and cell cycles are expressed at high levels in these cells. The aim of the present study is to explore the cytoprotection of TSM against hydrogen peroxide- (H2O2-) induced apoptosis and the molecular mechanisms underlying PC12 cells. Our findings revealed that TSM cotreatment with H2O2 restores the expression of bcl-2, inducible nitric oxide synthase (INOS), and mitochondria membrane potential. Meanwhile, it reduces intracellular [Ca(2+)] concentration, lactate dehydrogenase (LDH) release, and the expression of caspase-3 and bax. The results of the present study suggested that the cytoprotective effects of the TSM might be mediated, at least in part, by the bcl-2-mitochondria-ROS-INOS pathway. Due to its nontoxic characteristics, TSM could be further developed to treat the neurodegenerative diseases which are closely associated with the oxidative stress.


Skin Popping for the Hand Surgeon: A Case Report and Review.
Subcutaneous injection of illicit drugs, colloquially known as skin popping, is associated with skin and soft tissue infections of the upper extremity. Sequelae of these infections often present to hand surgeons in the late stages of disease, are associated with challenging clinical scenarios, and are a significant burden to both patients and providers. The authors present an illustrative case and review the literature regarding this growing phenomenon in upper extremity surgery. A case report detailing the surgical reconstruction of a large forearm wound in the setting of intravenous heroin use and skin popping is presented. Search terms related to upper extremity subcutaneous drug injection were used to find relevant articles in PubMed and EMBASE. A total of 488 articles were found, with 22 studies meeting the inclusion criteria. In this case report, the patient had a long history of skin popping to the forearm and presented with a chronic wound with exposed bone. The patient was treated with serial debridement, bony fixation, intravenous antibiotics, and soft tissue coverage using an arteriovenous loop and a muscle-only latissimus flap. Literature review yielded 22 studies comprising 38 patients with 55% (11/20) women and age range of 23 to 58 years. Heroin was the most commonly used drug (50.0%). The most common presentation was soft tissue infection (6/20 patients), manifestations of noninfected wounds (5/20), and wound botulism (4/20 of patients). Seventy percent of patients presented with multiple injection sites. Surgical management was described in 18% of cases, with all but one case describing drainage and debridement techniques. Only one case of formal reconstruction using a dermal template was described. Skin popping infections have unique pathogenesis, presentation, and management patterns that hand surgeons must be aware of when treating these patients. A literature review revealed a relative paucity of reports regarding risk factors and surgical management of "skin popping" sequelae. If patients are reconstructive candidates, complex reconstruction requiring free tissue transfer may be warranted.


Exhausting Physicians Employed in Hospitals in Japan Assessed by a Health Questionnaire.
Japanese physicians employed and working in general hospitals have become busier since 2005, as they had to teach and guide the increased number of medical residents graduated from medical schools. Working hours and chronic fatigue of employed physicians were surveyed compared with independent physicians working in their own out-patient clinics and with usual employed men in Japan, and their mental health was assessed. (1) 75 employed physicians in hospitals were surveyed of their working hours a week and compared with (2) 48 independent general practitioners (GP) who work in their own out-patient clinics. (3) 47 employed physicians aged 40s and 50s out of (1) were compared with group (4) or 277 men of the same age employed in an automobile company. A symptom check list questionnaire, the Total Health Index (THI), was used to assess their stress and mental health status. The THI has 130 questions including physical symptoms, mental complaints, lifestyle and habits. 130 items have been grouped into 12 scales: vague complaints, respiratory symptoms, depression, and 9 other scales. The average weekly working hours of employed physicians of (1) and GPs of (2) were 55.7 h and 51.3 h, respectively, and those who worked 60 h or more a week were 44.0% and 27.0%, respectively. They had significantly higher average scale scores than GPs with respect to vague complaints, irregular daily life, mental instability, depression, neurotics and psychosomatics scales. They also had significantly higher yes response rates for question items, "envy for richer friends", "feel my life is going badly", and other items than the GPs. 47 employed physicians of group (3) and 277 men workers of group (4) worked for 57.0 h and 46.0 h a week, respectively, in average, and 51.1% and 6.2% of group (3) and (4), respectively, worked for 60 h or more a week. The average scale scores of physicians of (3) were highly significantly poorer than group (4) in many scales of THI. Physicians employed also had significantly higher yes response rates for question items "feel too heavy work load", "stressed state", "irritated", "depressed", "lack of sleep", and "low back pain". Most of the physicians of group (3) were exhausted due to the hard work, showing a sharp contrast to group (4). Physicians employed in hospitals work for 57.0 h a week on average, although usual labors of the same age in a large farm work for 46.0 h a week. Physicians employed were exhausted or burnout and under poorer mental condition.


Soluble IL-7Rα/sCD127 in Health, Disease, and Its Potential Role as a Therapeutic Agent.
Soluble cytokine receptors can influence immune responses by modulating the biological functions of their respective ligands. These effects can be either agonistic or antagonistic and a number of soluble cytokine receptors have been shown to play critical roles in both maintenance of health and disease pathogenesis. Soluble IL-7Ra (sCD127) is one such example. With its impact on the IL-7/CD127 pathway, which is fundamental for the development and homeostasis of T cells, the role of sCD127 in health and disease has been extensively studied in recent years. Within this review, the role of sCD127 in maintaining host immune function is presented. Next, by addressing genetic factors affecting sCD127 expression and the associated levels of sCD127 production, the roles of sCD127 in autoimmune disease, infections and cancer are described. Finally, advances in the field of soluble cytokine therapy and the potential for sCD127 as a biomarker and therapeutic agent are discussed.


A new synonym for Enicospilus grammospilus (Enderlein, 1921) (Hymenoptera: Ichneumonidae: Ophioninae).
The megadiverse genus Enicospilus Stephens, 1835 (Hymenoptera: Ichneumonidae: Ophioninae) comprises over 700 valid species worldwide (e.g. Gauld Mitchell, 1981; Broad Shaw, 2016; Shimizu, 2017). Species of this genus are koinobiont endoparasitoids of moderately large sized lepidopteran larva (e.g. Gauld, 1985b; Broad Shaw, 2016). Members of this genus usually have "ophionoid facies", characterized by an orange-brown body, extremely large ocelli, long antennae, etc. (Gauld Huddleston, 1976). Ophionoid facies wasps including Enicospilus are attracted to light and considered to be crepuscular or nocturnal (e.g. Short et al., 2006; Shimizu Maeto, 2016; Shimizu Lima, 2018). These wasps usually exhibit a very limited number of diagnostic characters and as a consequence the delimitation and recognition of species is very difficult, and causes many taxonomic confusions including synonyms, homonyms and misidentifications.


Diagnostic significance of hemoglobin F and A2 levels in homo- and heterozygous beta-thalassemia during infancy.
For diagnosis of beta- and beta delta-thalassemia in the first year of life the physiological changes of hemoglobin F and A2 levels occurring in this age group have to be considered. The analysis of the hemoglobin pattern in 29 cases of thalassemia major and 285 cases of thalassemia trait, 47 of them aged less than one year, showed that all cases of homozygous beta-thalassemia aged less than one year could be diagnosed by definitely increased hemoglobin F levels exceeding the normal range for the appropriate age. In children older than ten years and in adults with heterozygous beta-thalassemia, the diagnosis could be made accurately by increased hemoglobin A2 levels in 97 percent. In children between one and ten years only 77 percent and in infants aged less than one year only 55 percent of the cases showed increases hemoglobin A2 levels. In contrast to adults, the hemoglobin F level seems to be helpful for the diagnosis of thalassemia trait. The younger the patient the more is the hemoglobin F level increased above the normal range for the appropriate age. It appears impossible to differentiate between beta- and beta delta-thalassemia trait when hemoglobin A2 is normal or low.


Gelation Properties of Soymilk and Soybean 11S Globulin from Japanese-grown Soybeans.
A new method to evaluate soybeans for making tofu (soybean curd) is proposed. Dynamic viscoelasticity measurements were carried out to examine the gelation process of soymilk, storage and loss moduli being observed as a function of time after adding glucono-δ-lactone. The gelation curves fitted well with first-order reaction kinetics. The saturated value of the storage modulus correlated well with gel hardness by a curdmeter. The saturated value of the storage modulus was mainly dependent on the concentration of 11S globulin, while the gelation rate was an increasing function of the concentration of glucono-δ-lactone at a fixed 11S globulin concentration.


[Medical abortion 15-22g.w. first experience with mifepriston administration in Bulgaria].
Medical abortion by definition is termination of pregnancy by means of administration of abortifacient pharmaceutical drugs. The most widely spread abortifacients are Mifepriston and Misoprostol. This is the gold standard for induced abortion worldwide, for first trimester, as well as for second. In Bulgaria Mifepriston is available as of June 2014. We represent here our first experience in administering Mifepriston for induced abortion in second trimester. We share our first impressions and discuss the results.


Sequential activation in V genes during postnatal life.
The BALB/c mouse strain represents an excellent model for studying the activation of V genes, because several myeloma proteins share the cross-reactive idiotype with antipolysaccharide antibodies of the same antigenic specificity. In addition, the majority of these antipolysaccharide antibody responses are independent of T help and, therefore, the maturation of helper T cells does not play a role in the study of these responses. Our results, as well as those obtained by other investigators, have shown that immunization of 1-day-old mice elicits an anti-beta 2 leads to 6 fructosan, 384Id anti-S tranaroa LPS, and X24IdX and X24IdI antigalactan response. T15Id+ phosphocholine, IdX+ anti-Ars, and 460Id+ anti-TNP (in response to immunization with TNP-LPS and TNP-Levan) antibody responses can be induced only in 6-to 8-day-old mice. One can obtain 2.4 SSSIII Id+ of anti-SSSIII and 347Id+ antiflagellin antibody responses only in 2-week-old mice. In 4-week-old mice IdX+ anti-beta 2 leads to 1 fructosan was elicited, and QPC52IdX+ anti-alpha 1-6 dextran in 3-month-old mice. These observations suggest a sequential activation of V genes during postnatal life. The theoretical and practical implications of these observations are discussed.


On Pause: How a Group of Medical Students Engaged with Their Community During the COVID-19 Pandemic.
During academic clinical suspensions related to the COVID-19 pandemic, a group of medical students in Washington, D.C. collaborated with a local federally qualified health center to launch a free COVID-19 testing site to increase access to testing in the community. The patients who accessed the testing site were predominantly Black/African American and Hispanic/Latino, some of whom were uninsured or without access to testing or a timely physician's referral. In this article, medical students reflect on their experiences at this testing site and provide commentary on how existing racial and socioeconomic health disparities have been exacerbated by the COVID-19 pandemic. While under the extremely unusual circumstance of a suspension from their clinical rotations, medical students elaborate on the lessons learned from this experience and the continued work required to engage deeply in the issues of equality and racial justice now and in the future.


Per-urethral endoscopic management of bladder stones: does size matter?
Large urinary bladder stones occupying the whole lumen are still encountered. Conventionally, an open suprapubic cystolithotomy (SPCL) has been the accepted treatment of choice. The other method described is suprapubic percutaneous lithotripsy. The present paper describes complete stone clearance in adults by the urethral route using a conventional nephroscope, a pneumatic lithotripter, and an evacuator. An additional procedure to treat outlet obstruction is performed when required. Although the procedure takes a long time, stone clearance is complete, and the procedure is free from any complications. This technique should be offered to all adults, as it has negligible morbidity.