Managing tinnitus: a comparison of different approaches to tinnitus management training.
A series of studies examining the interaction between the characteristics of individual tinnitus sufferers and the effectiveness of the methods used to assist them has been conducted. The first of these studies provided a baseline description of 96 people with tinnitus, according to a range of audiological and psychological variables. In the present paper four differing tinnitus management programmes are described and the related changes in tinnitus perception reported three months after tinnitus management training. For the majority of subjects, the tinnitus was less annoying and less distressing three months after attending tinnitus management training. However, the majority of subjects reported no change in tinnitus loudness, or tinnitus awareness and no change in their tinnitus coping ability. Subjects receiving low level white noise stimulation reported greater improvement in tinnitus coping ability than subjects who received information and relaxation training, although there was no associated improvement in tinnitus awareness. Subjects' beliefs about tinnitus and preferred coping style may have influenced the reported benefit or otherwise of the differing tinnitus management techniques.


1-(1-Benzoylpropen-2-yl)-3-methylisothiosemicarbazide.
The structure of the title S-alkylated isothiosemicarbazide, C(12)H(15)N(3)OS, was determined by single-crystal diffractometry and compared with the structures of other compounds containing the S-alkylthiosemicarbazide moiety. Such structures cluster into two groups, according to the different orientation of the [bond]SR group with respect to the hydrazine N atom of the thiosemicarbazide. The cis arrangement is preferred by most molecules in the solid state, in spite of the possibility of intramolecular N[bond]H...N interactions in the opposite orientation.


Trans fatty acids: effects on metabolic syndrome, heart disease and diabetes.
The major dietary sources of trans fatty acids (TFAs) in most countries are partially hydrogenated vegetable oils. TFA consumption is a modifiable dietary risk factor for metabolic syndrome, diabetes mellitus, and coronary heart disease. Here, we review the available data on various effects of TFAs, including metabolic and signaling pathways that mediate these effects, affected tissues, and relationships with clinical end points. TFA consumption causes metabolic dysfunction: it adversely affects circulating lipid levels, triggers systemic inflammation, induces endothelial dysfunction, and, according to some studies, increases visceral adiposity, body weight, and insulin resistance. Dietary TFAs influence the function of multiple cell types, including hepatocytes, adipocytes, macrophages and endothelial cells. Among dietary fats and nutrients, TFAs seem to have a unique cardiometabolic imprint that is linked to insulin-resistance and metabolic-syndrome pathways. Consistent with these adverse physiological effects, consumption of even small amounts of TFAs (2% of total energy intake) is consistently associated with a markedly increased incidence of coronary heart disease. Relationships between TFA consumption and diabetes mellitus have been less consistent, possibly owing to differences in study designs. Nevertheless, the documented adverse effects of TFAs underscore their potential to cause harm and the importance of policy measures to minimize consumption of industrially produced TFAs.


Short-term changes in bacterial community fingerprints and potential activities in an alfisol supplemented with solid waste leachates.
We investigated the effect on soil functioning of adding leachates from municipal solid waste incinerator (MSWI) ashes to laboratory columns (bare soil) and to field experimental plots (bare soil or grass cover). Leachate of MSWI-solidified air pollution control residues (SAPCr) contained more salts but less heavy metals than did MSWI-bottom ash (BA) leachate. Leachate-supplemented soils (BA soil, SAPCr soil) and control (water added) soil (W) were analyzed after 30 days. Potential denitrifying activity (PDA) and potential N2 fixation (acetylene reduction assay, ARA) were measured in controlled conditions. PDA was significantly lower in SAPCr soil than in W soil, both in the laboratory (-45%) and in bare soil in the field (-31%). ARA values were lower in bare SAPCr soil (-54%) and in bare BA (-25%) soil. Both activities remained unaffected by leachate supplementation in soil under permanent grass cover. Automated ribosomal intergenic spacer analysis (A-RISA) fingerprints and RFLP of nifH gene pools were used to assess changes in the structure of bacterial community. Multivariate analysis of these fingerprints revealed that SAPCr leachate had a stronger effect than BA leachate on the total and N2-fixing bacterial communities. Similar results were obtained for laboratory and bare soil field plots, but leachates did not affect nifH gene pools from soil under permanent grass cover. The stronger impact of SAPCr leachate on both structure of bacterial communities and activities supports the conclusion that observed effects would result from the abundance of salts rather than from heavy metal toxicity.


Prenatal diagnosis of placental chorioangioma: our experience.
Placental chorioangioma is the most common benign tumor of placenta. The relationship of vascularized chorioangiomas to adverse pregnancy outcome is well recognized. We report 3 cases of placental chorioangioma. Hypervascularization of the lesions in all patients and the immune hydrops with adverse fetal outcome in 2 cases are the complications of our mini-series. Ultrasonography and Doppler ultrasonography findings were useful in establishing the prenatal diagnosis and the prognosis.


Volume not guaranteed: closed endotracheal suction compromises ventilation in volume-targeted mode.
Closed endotracheal suction interferes with mechanical ventilation received by infants, but the change to ventilation may be different when ventilator modes that target expired tidal volume (VT(e)) are used. To measure airway pressure and tidal volume distal to the endotracheal tube (ETT) during and after closed suction in a volume-targeted ventilation mode with the Dräger Babylog 8000+, and to determine the time until VT(e) returns to the baseline level. In this benchtop study, closed suction was performed on 2.5- to 4.0-mm ETTs connected to a test lung. 5-8 French suction catheters were used at suction pressures of 80-200 mm Hg during tidal-volume-targeted ventilation. During catheter insertion and suction, circuit inflating pressure increased and tidal volume was maintained, except when a large catheter relative to the ETT was used, in which case tidal volume decreased. End-expiratory pressure distal to the ETT was reduced during suction by up to 75 cm H(2)O while circuit end-expiratory pressure was unchanged. Reduction in end-expiratory pressure distal to the ETT was greatest with large catheters and high suction pressures. Following suction, circuit and tracheal inflating pressures increased and tidal volume increased before returning to baseline in 8-12 s. Closed endotracheal suction interferes with ventilator function in volume-targeted mode, with substantially negative intratracheal pressure during suction, and the potential for high airway pressures and tidal volumes following the procedure. These effects should be considered and pressure limits set appropriately whenever using volume-targeted ventilation.


Study of insulin vascular sensitivity in aortic rings and endothelial cells from aged rats subjected to caloric restriction: Role of perivascular adipose tissue.
The prevalence of metabolic syndrome is dramatically increasing among elderly population. Metabolic syndrome in aged individuals is associated with hyperinsulinemia and insulin resistance both in metabolic tissues and in the cardiovascular system, with this fact being associated with the cardiometabolic alterations associated to this condition. Caloric restriction (CR) improves insulin sensitivity and is one of the dietetic strategies most commonly used to enlarge life and to prevent aging induced cardiovascular alterations. The aim of this study was to analyze the possible beneficial effects of CR in aging-induced vascular insulin resistance both in aortic rings and in primary culture of endothelial cells. In addition, the inflammatory profile of perivascular adipose tissue (PVAT) and its possible role in the impairment of vascular insulin sensitivity associated with aging was also assessed. Three experimental groups of male Wistar rats were used: 3 (3m), 24 (24m) fed ad libitum and 24months old rats subjected to 20% CR during their three last months of life (24m-CR). Aorta rings surrounded or not by PVAT were mounted in an organ bath and precontracted with phenylephrine (10-7.5M). Changes in isometric tension were recorded in response to cumulative insulin concentrations (10-8-10-5.5M) in the presence or absence of L-NAME (10-4M). Aortic rings and primary aortic endothelial cells were incubated in presence/absence of insulin (10-7M) and the activation of the PI3K/Akt and MAPK pathways as well as nitrite and nitrates concentrations and the mRNA levels of eNOS, insulin receptor, and GLUT-4 were assessed. CR prevented the aging-induced decrease in the vasodilator response to insulin and the aging-induced increase in the vasoconstrictor response to high insulin concentrations. Changes between 24m and 24m-CR aorta rings were abolished in the presence of L-NAME. CR induced-improvement in insulin vascular sensitivity was related with activation of the PI3K/Akt both in aortic rings and in aortic endothelial cells in response to insulin. CR attenuated the overexpression of iNOS, TNF-α and IL-1β in the PVAT of aged rats although aortic rings surrounded by PVAT from 24m rats showed and increased vasorelaxation in response to insulin compared to aortic rings from 3m and 24m-CR rats. In conclusion, a moderate protocol of CR improves insulin vascular sensitivity and prevents the aging induced overexpression of pro-inflammatory cytokines in PVAT.


High prevalence of vitamin D deficiency in Japanese female patients with Graves' disease.
We reported previously that vitamin D deficiency is a causal mechanism of postoperative tetany in patients with Graves' disease. The aim of the present study was to determine the prevalence of vitamin D deficiency by reviewing serum 25(OH)D levels in 208 patients with Graves' disease (146 women, 62 men) during a 1 year period. Serum 25(OH)D levels were significantly lower (p < 0.001) in female Graves' patients (31.8 +/- 13.3 nmol/l) than in male patients (41.3 +/- 15.0 nmol/l). Vitamin D deficiency (defined as a serum 25(OH)D value below 25 nmol/l) was found in 40% of female patients and in 18% of male patients (p < 0.005). There was a significant seasonal variation in the 25(OH)D concentrations in female patients [amplitude 6.38 (95% CI, 5.42-7.56)], with values below 25 nmol/l found in 58% of female patients during the winter months. There were significant (p < 0.001) differences in serum 25(OH)D levels between age groups in the female patients. The concentrations were lowest in patients in their twenties (25.1 +/- 8.2 nmol/l) and highest in patients in their fifties and sixties (43.2 +/- 13.7 nmol/l). Serum 25(OH)D concentrations might be monitored in patients with Graves' disease during antithyroid drug therapy, and vitamin D and/or calcium supplements are recommended for patients with vitamin D deficiency.


In situ ATR-FTIR studies on MgCl2-diisobutyl phthalate interactions in thin film Ziegler-Natta catalysts.
To study the surface structure of MgCl(2) support and its interaction with other active components in Ziegler-Natta catalyst, such as electron donors, we prepared a thin film analogue for Ziegler-Natta ethylene polymerization catalyst support by spin-coating a solution of MgCl(2) in ethanol, optionally containing a diester internal donor (diisobutyl-ortho-phthalate, DIBP) on a flat Si crystal surface. The donor content of these films was quantified by applying attenuated total internal reflection-Fourier transform infrared spectroscopy (ATR-FTIR) and X-ray photoelectron spectroscopy (XPS). Changes in the interaction of DIBP with MgCl(2) at various temperatures were monitored by in situ ATR-FTIR. Upon increasing the temperature, a shift in the (C═O) band toward lower wavenumbers was observed together with the depletion of (O-H) stretching band due to the desorption of residual ethanol. We assign this shift to gradual redistribution of adsorbed DIBP from adsorption sites on the MgCl(2) (104) surface toward the more acidic MgCl(2) (110) surface. The morphologies of MgCl(2) and MgCl(2)/DIBP films were studied by transmission electron microscopy (TEM) revealing a preferential orientation of ClMgCl layers (001) parallel to the lateral film dimensions. This orientation becomes more pronounced upon annealing. In the absence of donor, the MgCl(2) grow in to large crystals aligned in large domains upon annealing. Both crystal growth and alignment is impeded by the presence of donor.


Homogeneous field intensity control during multi-needle electrospinning via finite element analysis and simulation.
In the current study, finite element analysis is employed to simulate the process control of multi-needle electrospinning, by manipulating needle length, needle spacing, plastic casing of needle, and the way the voltage is applied to the needles, to facilitate the efficient production of homogeneous nanofibrous webs at high performance versus cost. The simulation results indicate that it is possible to control the field intensity homogeneity of multi-needle electrospinning process in terms of the vector sum of electric field intensity by adjusting the needle length, needle spacing, changing voltage application method and separating each needle with a plastic casing, etc. Measures such as capping each needle with a plastic casing, applying voltage directly to the needles, shortening the probed length of the needles at the edge sides, and reducing the distance between edge needles, as well as imparting additional voltage to the needles in the middle of the row could significantly decrease the field intensity of edge needles and thus improve the field intensity of the needles across one row and increase the potential of industrializing the needle type electrospinning technology.


Clinical findings, treatment and outcome in cats diagnosed with precursor-targeted immune-mediated anaemia in a referral hospital in the UK: 30 cases (2010-2021).
This retrospective study aimed to report clinical findings, treatment response and survival in cats diagnosed with precursor-targeted immune-mediated anaemia (PIMA) in a referral hospital in the UK. Feline cases diagnosed with presumed PIMA between January 2010 and February 2021 were retrospectively recruited. Signalment, clinical signs, diagnostic tests, treatment and outcome were recorded. Descriptive analytics were performed. Outcomes were documented according to survival to discharge, 30-day survival, total survival time, response to immunosuppressive treatment and frequency of relapses. Thirty cats met the inclusion criteria. A higher prevalence of females (19/30) was identified (p = 0.001). Most cats (25/30) presented with haematocrit below 0.15 L/L. Concurrent cytopenias occurred in 18 of 30 cats. Bone marrow diagnosis was erythroid hyperplasia in 24 of 30 cases. Survival to discharge was documented in 26 of 30 cats, of which 23 survived more than 30 days since diagnosis. Initial treatment included blood products (26/30) and prednisolone (26/30) or prednisolone with ciclosporin (3/30); 18 of 30 cats responded to treatment, with a normal haematocrit at a mean of 28 days. The initial haematocrit and the presence of concurrent cytopenia were not statistically different between responders and non-responders. The median survival time was 140 days (range 1-3930 days). The treatment response rate of feline PIMA was high (60%), with a mortality rate of 23% over the 30 days following diagnosis. Relapses occur frequently (77%) but the response rate after treatment modification was high (76%) and therefore ongoing treatment may be justified at that point. Long survival times (up to 3930 days) can be achieved.


A Measure to Assess HIV Treatment Readiness among Adolescents and Young Adults.
HIV infections among adolescents and young adults continue to grow and clinical guidelines recommend the immediate start of life-saving antiretroviral therapy (ART). Unfortunately, suboptimal medication adherence among youth is common and can lead to poorer health outcomes as well as onward transmission of HIV to sexual partners. Clinical tools to assess treatment readiness are needed and can assist with adherence intervention strategies for youth. An assessment tool that we previously developed, the HIV Treatment Readiness Measure (HTRM), was administered to 595 HIV-positive youth ages 13-24 recruited from adolescent medicine clinics in the United States. Participants were followed for a minimum of 6 months and had to have at least one viral load test completed to be included in this analysis. The HTRM demonstrated high internal consistency (Chronbach's alpha = 0.86). For participants currently on ART at study entry, higher overall treatment readiness scores predicted future viral suppression (OR 1.52). Individual scores on three of the measure's factors (Psychosocial Issues, Connection with Care, and HIV Medication Beliefs) were also significant predictors of viral suppression. For those participants not on ART at study entry, the HIV Medication Beliefs factor significantly predicted who would eventually start ART (OR 2.26) but overall treatment readiness scores did not predict viral suppression in that group.


Serum triglycerides as a risk factor for cardiovascular diseases in the Asia-Pacific region.
The importance of serum triglyceride levels as a risk factor for cardiovascular diseases is uncertain. We performed an individual participant data meta-analysis of prospective studies conducted in the Asia-Pacific region. Cox models were applied to the combined data from 26 studies to estimate the overall and region-, sex-, and age-specific hazard ratios for major cardiovascular diseases by fifths of triglyceride values. During 796,671 person-years of follow-up among 96,224 individuals, 670 and 667 deaths as a result of coronary heart disease (CHD) and stroke, respectively, were recorded. After adjustment for major cardiovascular risk factors, participants grouped in the highest fifth of triglyceride levels had a 70% (95% CI, 47 to 96) greater risk of CHD death, an 80% (95% CI, 49 to 119) higher risk of fatal or nonfatal CHD, and a 50% (95% CI, 29% to 76%) increased risk of fatal or nonfatal stroke compared with those belonging to the lowest fifth. The association between triglycerides and CHD death was similar across subgroups defined by ethnicity, age, and sex. Serum triglycerides are an important and independent predictor of CHD and stroke risk in the Asia-Pacific region. These results may have clinical implications for cardiovascular risk prediction and the use of lipid-lowering therapy.


Cross-Border Higher Education: The Expansion of International Branch Campuses.
The international expansion of higher education has intensified in recent decades with a rapidly growing number of international branch campuses appearing on the scene. This study investigates the economic, cultural and institutional, and educational determinants of transnational higher education on both the extensive margin (number of international branch campuses), and the intensive margin (the total number of educational programmes offered). Using the gravity equation, we applied fixed-effect empirical methods to a panel dataset that combined and extended the raw data from campuses and master's programmes in 33 source countries and 76 host countries in the period from 1948 to 2016. Estimates reveal that although cultural, economic and institutional ties foster cross-border educational relationships, their effect differs significantly from one margin to another. The study highlights the relevance of globalisation, research activities, and aggregate demand in international higher education.


The prospective payment system: implications for therapeutic recreation.
In 1983, medicare began paying general hospitals by a prospective payment system based on diagnostically-related groupings (DRGs). The majority of therapeutic recreation settings (including psychiatric hospitals, rehabilitation centers, long-term care hospitals, and children's hospitals) have been exempted. However, in 1985, a plan and subsequent decision will be made on how to integrate these settings into this new system. This article provides an historical review of the medicare program, the rationale behind this new system, the method for implementing the DRGs, and the implications and strategies for therapeutic recreation.


In vitro assessment of the DNA damage and senility of CD117+ stem cells collected from diabetic mice.
Angiogenesis impairment is a common feature of diabetes mellitus (DM), whereas CD117+ bone marrow cells (BMCs) injury might be responsible for such complication. In this study, we studied the effect of hyperglycemia on the DNA damage and senility of CD117+ bone marrow cells. We isolated CD117+ BMCs from the Streptozotocin (STZ) induced diabetes and healthy control mice. Oxidative stress was detected by flow cytometric analysis. γ-H2AX, which is the DNA damage mark, was detected by using Western blotting and immunofluorescence histochemistry. We also detected the expression of γ-H2AX and p16 by using Western blotting. Compared with the control mice, the level of reactive oxygen species (ROS) was increased significantly in the CD117+ BMCs collected from the diabetic mice (p<0.05), and the percentage of γ-H2AX positive cells was higher significantly (p<0.01). The expression of γ-H2AX and p16 was increased significantly in the CD117+ BMCs from the diabetic mice. Our experiments demonstrated the oxidative stress in CD117+ BMCs under DM conditions, while accelerating the DNA damage and senility in CD117+ BMCs as well.


Assessment of free-living physical activity in humans: an overview of currently available and proposed new measures.
The number of physical activity measures and indexes used in the human literature is large and may result in some difficulty for the average investigator to choose the most appropriate measure. Accordingly, this review is intended to provide information on the utility and limitations of the various measures. Its primary focus is the objective assessment of free-living physical activity in humans based on physiological and biomechanical methods. The physical activity measures have been classified into three categories: Measures based on energy expenditure or oxygen uptake, such as activity energy expenditure, activity-related time equivalent, physical activity level, physical activity ratio, metabolic equivalent, and a new index of potential interest, daytime physical activity level. Measures based on heart rate monitoring, such as net heart rate, physical activity ratio heart rate, physical activity level heart rate, activity-related time equivalent, and daytime physical activity level heart rate. Measures based on whole-body accelerometry (counts/U time). Quantification of the velocity and duration of displacement in outdoor conditions by satellites using the Differential Global Positioning System may constitute a surrogate for physical activity, because walking is the primary activity of man in free-living conditions. A general outline of the measures and indexes described above is presented in tabular form, along with their respective definition, usual applications, advantages, and shortcomings. A practical example is given with typical values in obese and non-obese subjects. The various factors to be considered in the selection of physical activity methods include experimental goals, sample size, budget, cultural and social/environmental factors, physical burden for the subject, and statistical factors, such as accuracy and precision. It is concluded that no single current technique is able to quantify all aspects of physical activity under free-living conditions, requiring the use of complementary methods. In the future, physical activity sensors, which are of low-cost, small-sized, and convenient for subjects, investigators, and clinicians, are needed to reliably monitor, during extended periods in free-living situations, small changes in movements and grade as well as duration and intensity of typical physical activities.


Occupational Burden of Chronic Obstructive Pulmonary Disease in the Commonwealth of Independent States: Systematic Review and Meta-Analysis.
Background: Population-based studies from the Russian Federation and neighboring countries on the occupational burden of chronic obstructive pulmonary disease (COPD) are seldom or not included in the systematic reviews. The aim of this review was to summarize published population-based studies from the Commonwealth of Independent States (CIS) in order to ascertain the occupational burden of COPD. Methods: We systematically searched www.elibrary.ru and PubMed for population-based studies on the epidemiology of COPD in nine countries using PRISMA. Quality of studies was assessed using the original tool. The odds of COPD in the included studies from vapors, gases, dusts, and fumes (VGDF) was pooled using meta-analysis (fixed effects model), whereas the population attributable fraction percent (PAF%) was pooled with meta-proportion using the random effects model in Stata 14.2. Results: Five studies, three from Russia, one from Kazakhstan, and one more from Azerbaijan and Kazakhstan (total N = 18,908) with moderate to high quality and published from 2014 to 2019 (none from Armenia, Belarus, Kyrgyzstan, Moldova, Tajikistan, and Uzbekistan), were included. Spirometry-defined COPD was the outcome in four of them. The pooled odds ratio (OR) of COPD from VGDF was 1.69 [95% confidence interval (CI) 1.34;2.13], greater in Kazakhstan [OR 1.96 (95% CI 1.35;2.85, N = 2 studies)] compared to Russia [OR 1.52 (95% CI 1.13;2.05, N = 2 studies)]. The pooled PAF% was 6% (95% CI 2; 14%) from three studies. Conclusions: Population-based studies in the CIS get little attention with very few studies published. Although the effect was greater in Kazakhstan compared to Russia, the overall effect did not differ from studies published in the rest of the world. Research capacity to study occupational risks of COPD should be strengthened to produce more evidence of higher quality.


Percutaneous internal fixation with Y-STRUT® device to prevent both osteoporotic and pathological hip fractures: a prospective pilot study.
We studied Y-STRUT® (Hyprevention, France), a new percutaneous internal fixation device, in combination with bone cementoplasty to prevent hip fracture. Between February 2013 and February 2015, a total of 16 femoral necks in 4 osteoporotic and 12 oncologic patients have been considered for prophylactic consolidation in this prospective multicentre pilot study involving 4 different hospitals. These consolidations were performed percutaneously under fluoroscopic guidance using Y-STRUT®, a dedicated internal fixation device. For osteoporotic patients, orthopaedic surgeons performed the prophylactic consolidations immediately after surgical treatment of a hip fracture (same anaesthesia) in the opposite side. For oncologic patients, without current hip fracture but considered at risk (Mirels score ≥8), interventional radiologists performed the procedures. We report the preliminary results of feasibility, safety and tolerance of these preventive consolidations using Y-STRUT®. Four patients (mean 83 years old) had prophylactic consolidation because of a severe osteoporosis (mean T-score -3.30) resulting in first hip fractures. Ten patients (mean 61 years old) were treated because of impending pathological fractures (mean Mirels score 9) related to femoral neck osteolytic metastases. All the procedures were performed with success. Wound healing was achieved in all cases with no access site complication. Radiographic exams performed at 3 months follow-up revealed that Y-STRUT® was well integrated in the bone. For the osteoporotic cohort, mean pain was 0.9 ± 0.7 at 3 weeks. For the oncologic cohort, it decreases from 3.6 ± 2.9 at baseline to 2.4 ± 0.9 at 2 months. Preliminary results demonstrate the feasibility and safety of Y-STRUT® implantation as well as the tolerance of the device.


Nicotine Metabolism-informed Care for Smoking Cessation: A Pilot Precision RCT.
Varenicline doubles cessation over nicotine replacement therapy (NRT) patch for "normal," but not "slow," nicotine metabolizers, as assessed by the nicotine metabolite ratio (NMR). Metabolism-informed care (MIC) could improve outcomes by matching normal metabolizers with non-nicotine medication (e.g., varenicline) and slow metabolizers with NRT patch. We conducted a feasibility randomized controlled trial of MIC versus guideline based care (GBC) among 81 outpatient adult daily smokers with medical comorbidity. Participants reported perceptions of MIC, underwent blood draw for NMR, and received expert cessation counseling. For MIC participants, medication selection was informed by NMR result (normal (≥0.31) vs. slow (< 0.31)). The primary outcome was MIC feasibility, reflected by attitudes toward MIC and by match rates between NMR and medication. Secondary endpoints (cessation confidence, medication use, smoking status) were assessed over 6 months to inform future studies. Participants were median age 53 years, 46% female, 28% black, and ~90% endorsed MIC. Despite high varenicline prescription rates (~60%) in both arms, NMR-medication matching was higher in MIC (84%) versus GBC (58%) participants (p=0.02); unadjusted odds ratio (OR) 3.67, 95% confidence interval [1.33, 11.00; p-value=0.02]. Secondary endpoints were similar at 1, 3, and 6 months. MIC, an NMR-based precision approach to smoking cessation, was acceptable to 90% of smokers and improved NMR-medication match rates more than 3-fold compared to GBC, even with generally high use of varenicline. These data support the feasibility of MIC, which could maximize efficacy of smoking cessation medication while minimizing side effects and cost. Among treatment-seeking daily smokers with medical comorbidity, most viewed metabolism-informed care (MIC), guided by the nicotine metabolism ratio (NMR), favorably, and were willing to accept MIC-guided medication. Compared to GBC participants (58%), more MIC participants (84%) were prescribed NMR-matched medication (i.e., normal metabolizers received varenicline; slow metabolizers received NRT patch). MIC increased the odds of optimized matching between NMR and medication more than 3-fold over GBC. Because the number needed to treat (NNT) to help one normal metabolizer quit smoking is only 4.9 for varenicline versus 26 for patch, broad implementation of MIC will improve drug efficacy in normal metabolizers as well as minimize side effects in slow metabolizers.


A feasibility study of the SDI test for the evaluation of gastrointestinal cancer sensitivity to anticancer drugs.
The succinic dehydrogenase inhibition (SDI) test has been widely used to evaluate the sensitivity of cancer cells to anticancer agents. Recently, the techniques for tissue culture have progressed; the ability to make formazan has improved with the use of methylthiazol tetrazolium bromide (MTT) instead of triphenyl tetrazolium chloride (TTC) in this assay. Therefore, we modified the SDI test in order to evaluate the drug response to gastrointestinal cancer and applied it in a clinical study. In this assay, the optimal concentration levels of mytomycin-C and Adriamycin for the clinical materials are 10 micrograms/ml, that is, 10 times higher than for the cancer cell line, and that of Cisplatin is 30 micrograms/ml, for Cisplatin is unstable in the culture medium. To evaluate its antitumor effect, it was found necessary to expose the cancer cells to 5-fluorouracil (5-FU) for 3 days. We applied this assay for the clinical materials; the evaluable rate of this assay is 83.3%. The peculiarity of this assay is its high evaluable rate. These results suggest that this test may be useful for clinical application.


Cryptosporidiosis in birds--a review.
The taxonomy, morphology and life cycle, host species, incidence, pathology, transmission, immunity, diagnosis and control of cryptosporidiosis in birds are reviewed.


[The inhibitory effect and the mechanism of ethanol absorption by L-carnosine zinc complex in mouse gastrointestinal tract].
The effect of L-carnosine-zinc complex(Car-Zn) on ethanol absorption was investigated after oral administration(adm) to mice. One hour after oral adm of Car-Zn, and 14C-ethanol was given orally or intraperitoneally(i.p.). After passage of time, the blood was drawn from the tail vein, and 14C-radioactivities determined. The Car-Zn showed a dose-dependent inhibition of the appearance of 14C-radioactivities in blood following oral 14C-ethanol loading, while Zn acetate did not induce any alteration as compared with control. Car-Zn pretreatment did not induce any change in the blood 14C-radioactivity when ethanol was given i.p. The 14C-radioactivity and zinc in gastrointestinal tract after oral adm of Car-Zn and 14C-ethanol showed significantly higher levels than those of control for 7 hr. Distribution of 14C-radioactivities in other organs of Car-Zn treated mice were lower than those of control 3 hr after adm, while it was similar or higher than those of control 7 hr after adm. The excretions of 14C-radioactivity through expiration in Car-Zn group was a lower than that of control. Also, the urinary and fecal excretions of 14C-radioactivity were low values at 5.0% and 0.5% of the administered dose 72 hr after adm, respectively. Also, the 14C-radioactivities remaining in the organs did not detect or were very low values. In vitro study, Car-Zn stimulated the metabolism of ethanol to acetaldehyde and acetic acid in 9,000 g supernatant of small intestine. The major route of excretions of 14C-radioactivity may be excreted into the expired air. The results suggest that Car-Zn shows a long-term adhesive and permeable action on gastrointestinal tract in the mouse; as a result, this may inhibited ethanol absorption.


Is p53 Involved in Tissue-Specific Insulin Resistance Formation?
p53 constitutes an extremely versatile molecule, primarily involved in sensing the variety of cellular stresses. Functional p53 utilizes a plethora of mechanisms to protect cell from deleterious repercussions of genotoxic insults, where senescence deserves special attention. While the impressive amount of p53 roles has been perceived solely by the prism of antioncogenic effect, its presence seems to be vastly connected with metabolic abnormalities underlain by cellular aging, obesity, and inflammation. p53 has been found to regulate multiple biochemical processes such as glycolysis, oxidative phosphorylation, lipolysis, lipogenesis, β-oxidation, gluconeogenesis, and glycogen synthesis. Notably, p53-mediated metabolic effects are totally up to results of insulin action. Accumulating amount of data identifies p53 to be a factor activated upon hyperglycemia or excessive calorie intake, thus contributing to low-grade chronic inflammation and systemic insulin resistance. Prominent signs of its actions have been observed in muscles, liver, pancreas, and adipose tissue being associated with attenuation of insulin signalling. p53 is of crucial importance for the regulation of white and brown adipogenesis simultaneously being a repressor for preadipocyte differentiation. This review provides a profound insight into p53-dependent metabolic actions directed towards promotion of insulin resistance as well as presenting experimental data regarding obesity-induced p53-mediated metabolic abnormalities.


Synthesis of 1,2-cis-homoiminosugars derived from GlcNAc and GalNAc exploiting a β-amino alcohol skeletal rearrangement.
The synthesis of 1,2-cis-homoiminosugars bearing an NHAc group at the C-2 position is described. The key step to prepare these α-D-GlcNAc and α-D-GalNAc mimics utilizes a β-amino alcohol skeletal rearrangement applied to an azepane precursor. This strategy also allows access to naturally occurring α-HGJ and α-HNJ. The α-D-GlcNAc-configured iminosugar was coupled to a glucoside acceptor to yield a novel pseudodisaccharide. Preliminary glycosidase inhibition evaluation indicates that the α-D-GalNAc-configured homoiminosugar is a potent and selective α-N-acetylgalactosaminidase inhibitor.


Curcumin limits weight gain, adipose tissue growth, and glucose intolerance following the cessation of exercise and caloric restriction in rats.
Weight regain, adipose tissue growth, and insulin resistance can occur within days after the cessation of regular dieting and exercise. This phenomenon has been attributed, in part, to the actions of stress hormones as well as local and systemic inflammation. We investigated the effect of curcumin, a naturally occurring polyphenol known for its anti-inflammatory properties and inhibitory action on 11β-HSD1 activity, on preserving metabolic health and limiting adipose tissue growth following the cessation of daily exercise and caloric restriction (CR). Sprague-Dawley rats (6-7 wk old) underwent a "training" protocol of 24-h voluntary running wheel access and CR (15-20 g/day; ~50-65% of ad libitum intake) for 3 wk ("All Trained") or were sedentary and fed ad libitum ("Sed"). After 3 wk, All Trained were randomly divided into one group which was terminated immediately ("Trained"), and two detrained groups which had their wheels locked and were reintroduced to ad libitum feeding for 1 wk. The wheel locked groups received either a daily gavage of a placebo ("Detrained + Placebo") or curcumin (200 mg/kg) ("Detrained + Curcumin"). Cessation of daily CR and exercise caused an increase in body mass, as well as a 9- to 14-fold increase in epididymal, perirenal, and inguinal adipose tissue mass, all of which were attenuated by curcumin ( P < 0.05). Insulin area under the curve (AUC) during an oral glucose tolerance test, HOMA-IR, and C-reactive protein (CRP) were elevated 6-, 9-, and 2-fold, respectively, in the Detrained + Placebo group vs. the Trained group (all P < 0.05). Curcumin reduced insulin AUC, HOMA-IR, and CRP vs. the placebo group (all P < 0.05). Our results indicate that curcumin has a protective effect against weight regain and impaired metabolic control following a successful period of weight loss through diet and exercise, perhaps via inhibition of glucocorticoid action and inflammation. NEW & NOTEWORTHY Weight regain after dieting and exercise is a common phenomenon plaguing many individuals. The biological mechanisms underlying weight regain are incompletely understood and are likely multifactorial. In this paper, we examined the metabolic implications of curcumin, a compound known for its anti-inflammatory properties and inhibitory action on the enzyme 11β-HSD1, in a rodent model of adiposity rebound after the cessation of diet and exercise.


Electronic aids to hearing.
Despite many scientific developments in the biology of hearing, there remain no wide-spread medical or surgical interventions for listeners with sensorineural hearing impairments. In addition to describing technical advances, this chapter identifies important aspects of candidature for hearing aids and some issues of service delivery.


Serum beta-2 microglobulin in malignant lymphomas: an old but powerful prognostic factor.
Beta-2 microglobulin is synthesized in all nucleated cells and forms the light chain subunit of the major histocompatibility complex class I antigen. Despite its potential role as a convenient and non-invasive prognostic indicator in malignant lymphomas, the influence of serum β2 microglobulin is currently underestimated, and therapeutic decision making is rarely affected by this marker. Recent studies that included relatively large numbers of patients with specific histologic subtypes showed that serum β2 microglobulin is a potent prognostic marker in malignant lymphomas. In follicular lymphoma, this effort led to the incorporation of serum β2 microglobulin as an indicator in a new prognostic model. In this review, we summarize the current evidence supporting the role of serum β2 microglobulin as a prognostic factor in patients with malignant lymphoma and discuss perspectives for future investigations.


[Professional burn-out of general practitioners in urban areas: prevalence and determinants].
A telephone survey was carried out in 2007 to evaluate prevalence of burnout in private GPs in South-eastern France and its determinants. Doctors were selected at random, and this list was stratified according to gender, age and size of the place of practice. Burnout was evaluated with the French validated version of the Maslach Burnout Inventory. 511 GPs participated (96,4%). The prevalence of the complete burnout syndrome was 1% (CI 95% [0,3-2,3]). Dealing with long working hours on a weekly basis and high-levels of mental strain, managing palliative care, unrealistic patients' expectations, work-home conflicts, having one's abilities questioned by patients, confronting judicial situations and legal cases or living with a partner, were all associated with one or several dimensions of burnout syndrome.


Primary Coenzyme Q10 Deficiency-7 and Pathogenic COQ4 Variants: Clinical Presentation, Biochemical Analyses, and Treatment.
Primary Coenzyme Q10 Deficiency-7 (COQ10D7) is a rare mitochondrial disorder caused by pathogenic COQ4 variants. In this review, we discuss the correlation of COQ4 genotypes, particularly the East Asian-specific c.370G > A variant, with the clinical presentations and therapeutic effectiveness of coenzyme Q10 supplementation from an exon-dependent perspective. Pathogenic COQ4 variants in exons 1-4 are associated with less life-threating presentations, late onset, responsiveness to CoQ10 therapy, and a relatively long lifespan. In contrast, pathogenic COQ4 variants in exons 5-7 are associated with early onset, unresponsiveness to CoQ10 therapy, and early death and are more fatal. Patients with the East Asian-specific c.370G > A variant displays intermediate disease severity with multi-systemic dysfunction, which is between that of the patients with variants in exons 1-4 and 5-7. The mechanism underlying this exon-dependent genotype-phenotype correlation may be associated with the structure and function of COQ4. Sex is shown unlikely to be associated with disease severity. While point-of-care high-throughput sequencing would be useful for the rapid diagnosis of pathogenic COQ4 variants, whereas biochemical analyses of the characteristic impairments in CoQ10 biosynthesis and mitochondrial respiratory chain activity, as well as the phenotypic rescue of the CoQ10 treatment, are necessary to confirm the pathogenicity of suspicious variants. In addition to CoQ10 derivatives, targeted drugs and gene therapy could be useful treatments for COQ10D7 depending on the in-depth functional investigations and the development of gene editing technologies. This review provides a fundamental reference for the sub-classification of COQ10D7 and aim to advance our knowledge of the pathogenesis, clinical diagnosis, and prognosis of this disease and possible interventions.


A behavioral economic analysis of texting while driving: Delay discounting processes.
The purpose of the present study was to examine an impulsive decision-making process underlying texting while driving from a behavioral economic perspective. A sample of 108 college students completed a novel discounting task that presented participants with a hypothetical scenario in which, after receiving a text message while driving, they rated the likelihood of replying to a text message immediately versus waiting to reply for a specific period of time. Participants also completed a delay discounting task in which they made repeated hypothetical choices between obtaining a larger amount of money available after a delay and an equal or lesser amount of money available immediately. The results show that the duration of the delay is a critical variable that strongly determines whether participants choose to wait to reply to a text message, and that the decrease in the likelihood of waiting as a function of delay is best described by a hyperbolic delay discounting function. The results also show that participants who self-reported higher frequency of texting while driving discounted the opportunity to reply to a text message at greater rates, whereas there was no relation between the rates of discounting of hypothetical monetary rewards and the frequency of texting while driving. The results support the conclusion that texting while driving is fundamentally an impulsive choice.


Type II regulatory subunits are not required for the anchoring-dependent modulation of Ca2+ channel activity by cAMP-dependent protein kinase.
Preferential phosphorylation of specific proteins by cAMP-dependent protein kinase (PKA) may be mediated in part by the anchoring of PKA to a family of A-kinase anchor proteins (AKAPs) positioned in close proximity to target proteins. This interaction is thought to depend on binding of the type II regulatory (RII) subunits to AKAPs and is essential for PKA-dependent modulation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptor, the L-type Ca2+ channel, and the KCa channel. We hypothesized that the targeted disruption of the gene for the ubiquitously expressed RIIalpha subunit would reveal those tissues and signaling events that require anchored PKA. RIIalpha knockout mice appear normal and healthy. In adult skeletal muscle, RIalpha protein levels increased to partially compensate for the loss of RIIalpha. Nonetheless, a reduction in both catalytic (C) subunit protein levels and total kinase activity was observed. Surprisingly, the anchored PKA-dependent potentiation of the L-type Ca2+ channel in RIIalpha knockout skeletal muscle was unchanged compared with wild type although it was more sensitive to inhibitors of PKA-AKAP interactions. The C subunit colocalized with the L-type Ca2+ channel in transverse tubules in wild-type skeletal muscle and retained this localization in knockout muscle. The RIalpha subunit was shown to bind AKAPs, although with a 500-fold lower affinity than the RIIalpha subunit. The potentiation of the L-type Ca2+ channel in RIIalpha knockout mouse skeletal muscle suggests that, despite a lower affinity for AKAP binding, RIalpha is capable of physiologically relevant anchoring interactions.


Key Elements and Mechanisms of a Peer-Support Intervention to Reduce Loneliness and Isolation among Low-Income Older Adults: A Qualitative Implementation Science Study.
This paper describes the evaluation of a longitudinal peer-support program developed to address loneliness and isolation among low-income, urban community-dwelling older adults in San Francisco. Our objective was to determine barriers, challenges, and successful strategies in implementation of the program. In-depth qualitative interviews with clients (n = 15) and peers (n = 6) were conducted and analyzed thematically by program component. We identified barriers and challenges to engagement and outlined strategies used to identify clients, match them with peers, and provide support to both peers and clients. We found that peers played a flexible, non-clinical role and were perceived as friends. Connections to community resources helped when clients needed additional support. We also documented creative strategies used to maintain inter-personal connections during the COVID-19 pandemic. This study fills a gap in understanding how a peer-support program can be designed to address loneliness and social isolation, particularly in low-income, urban settings.


Algorithmic diagnosis of jaundice.
Extensive clinical and clinical chemical information was collected from 1002 jaundiced patients. By applying Bayes' theorem and logistic discriminant analysis, a diagnostic algorithm was developed based upon 21 of the 107 variables collected. This algorithm permitted a probabilistic classification of jaundiced patients into four diagnostic categories: acute non-obstructive, chronic non-obstructive, benign obstructive and malignant obstructive jaundice. Of the 985 patients with a final diagnosis a correct probabilistic diagnosis (obstruction vs. non-obstruction) was suggested by the algorithm in 867 patients (88%). Adopting a probability limit of 0.80, 683 patients (69%) were correctly classified, 34 patients (3.5%) were wrongly so, and 268 patients (27%) could not be classified with a probability above 0.80 (doubtful cases). The algorithm was also tested in a further series of 110 jaundiced patients and found to perform equally well: 88 patients classified, 22 patients remaining doubtful. Patients with doubtful diagnoses should be referred to a non-invasive test such as ultrasound examination, whereas patients with definite diagnoses can be referred to invasive tests (liver biopsy, direct cholangiography) as appropriate. The diagnostic algorithm seems to be a valuable aid for the preliminary differential diagnosis of the jaundiced patient and can be used in the planning of a diagnostic strategy for the individual patient.


Cathepsin B- and L-like activities at local gingival sites of chronic periodontitis patients.
The cysteine proteinases cathepsins B and L have the potential to degrade connective tissue in chronic periodontitis and this may progress episodically at individual tooth sites. The activities of cathepsin B- and L-like proteinases in homogenised gingival tissue from control and periodontitis patients were measured biochemically using the selective peptide substrate Z-Phe-Arg-AFC and the selective cathepsin L inhibitor Z-Phe-Phe-CHN2. Each tooth site was divided, where appropriate, into gingival tissue and granulomata. These were assayed separately and the measurements related to the DNA and protein contents of the tissues. Enzyme activity in healthy control tissue was significantly lower than in diseased tissue. Enzyme activity in gingival tissue and total tissue from periodontitis patients decreased with increasing pocket depth, clinical attachment level, gingival index and bleeding index whilst cathepsin B activity in granulomata increased with increasing pocket depth and clinical attachment level but not with increasing gingival index or gingival bleeding index. Mean enzyme activity in gingival tissue was 1.6-2.8 times greater than in granulomata. Mean patient enzyme activity in diseased patients did not correlate positively with their mean pocket depth, clinical attachment level, gingival index or gingival bleeding index. These results are best explained by the probable cellular origins of the enzymes and the likely influence of their serum and tissue inhibitors during the disease process.


Perceptual and Acoustic Outcomes of Early-Stage Glottic Cancer After Laser Surgery or Radiotherapy: A Meta-Analysis.
Laser surgery (LS) or radiotherapy (RT) is normally recommended in early glottic cancer. The objective of this study was to perform a comprehensive meta-analysis of acoustic and perceptual outcomes to compare voice quality of LS or RT in early-stage glottic cancer. Data sources were obtained after searching PubMed, Google Scholar, EBSCO, and RISS using the following search terms: glottic cancer, glottic carcinoma, endoscopic surgery, laser surgery, radiotherapy, radiation, voice, voice quality, and grade, roughness, breathiness, asthenia, and strain (GRBAS) scale. Articles that compared voice outcomes between LS and RT were identified. This meta-analysis included 15 articles with 744 patients, including 400 in the LS group and 344 in the RT group. Random effects models were selected. Forest plots included standardized mean differences, standard errors, variance, 95% confidence intervals (lower limit to upper limit), z-values, and P-values. In perceptual analysis, grade (G) and asthenia (A) of RT were significantly better than LS. There was no statistically significant difference in roughness (R), breath (B), or strain (S) between LS and RT groups. Jitter, shimmer, and noise to harmonic ratio measurements showed significant differences, resulting in enhanced posttreatment effect of RT compared to LS. Results of our meta-analysis suggested that RT might lead to superior voice quality than LS in early glottic cancer.


Finite element representation of bone substitute remodelling in the jaw bone.
The finite element (FE) method was originally developed on a physical basis for the computation of structure-mechanical problems. Meanwhile, it has been widely applied to medical issues. This study sought a suitable method to build a FE model for remodelling processes in osseous defects supplemented with bone substitute material. For this purpose, the second right premolars were extracted from four pig mandibles (Sus scrofa domesticus) and the extraction alveoli were provided with synthetic bone substitute material. After 70 days, a segmented osteotomy of this area was performed for specimen collection. Radiographs of the specimens were taken in defined planes before and after fixation and embedded with Technovit 9100. Fixation-related shrinkage was quantified from the radiographs using reference lines. Computer tomographic (CT) and microCT images of the fixed and embedded specimens were obtained. From these data, a FE model was built. The construction of a FE model is sufficient to represent bone remodelling after supply of bone substitute material. The use of microCT data permits building a clearly more precise model.


The importance of cortical bone orthotropicity, maximum stiffness direction and thickness on the reliability of mandible numerical models.
To identify mechanical and geometrical variables affecting the biofidelity of numerical models of human mandible. Computed results sensibility to cortical bone orthotropy and thicknesses is investigated. Two mandible numerical models of different bone complexities are setup. In the low-complexity model, cortical bone is coupled with isotropic materials properties; constant thickness for cortical bone is adopted along the mandible structure. In the higher complexity model, the cortical bone is considered as an orthotropic material according to an independent mechanical characterization performed on fresh human dentate mandibles. Cortical thickness distribution, the values of the principal elastic moduli and principal directions of orthotropy are considered as piecewise heterogeneous. Forces for masseter (10 N), medial pterigoid (6 N), anterior (4 N) and posterior (4 N) temporalis muscles are applied to the models. Computed strains fields are compared with those experimentally measured in an independent test performed on a real human mandible in the same loading conditions. Under closure muscles forces both models shows similar strain distribution. On the contrary, strain fields values are significantly different between the presented models. The mandible structure is sensible to compact bone orthotropy and thickness at the facial side of condylar neck, retro molar area and at the lingual side of middle portion of the corpus in molars area, anterior margin of the ramus. In these areas, it is advisable to use orthotropic properties for cortical bone to accurately describe the strain state.


Bimolecular homolytic substitution (S(H)2) reactions with hydrogen atoms. time-resolved electron spin resonance detection in the pulse radiolysis of alpha-(methylthio)acetamide.
Pulse radiolysis of aqueous solutions of alpha-(methylthio)acetamide produced unexpectedly large quantities of acetamide radicals that were identified by time-resolved electron spin resonance (TRESR) spectroscopy. The pH dependence of the TRESR-measured radical yields, results from selective scavenging reactions, and density functional theory predictions of the reaction thermochemistry prove that bimolecular homolytic substitution, S(H)2, of the acetamide radical fragment by a H atom is the most likely formation pathway.


Kinetics of the effect of ara C on chromosome aberration yield in irradiated human lymphocytes.
In unstimulated lymphocytes the enhancing effect of ara C on the yield of X-ray-induced dicentric aberrations was maximal if ara C was added immediately or up to 2 h after irradiation. When ara C was added later the enhancing effect decreased and practically vanished by 5 h. In stimulated lymphocytes the ara C effect declined faster and practically vanished by 3 h. If ara C was added for 1 h immediately after irradiation, then the aberration yield observed in G0, early G1 and late G1 cells was similar whereas it increased significantly from G0 to late G1 cells without ara C post-treatment. The results are discussed in relation to the classical model of aberration formation.


Contrast-induced acute kidney injury following iodine opacification other than by intravascular injection.
Contrast-induced acute kidney injury (CI-AKI) classically occurs following the intravascular administration of iodinated contrast medium (CM). However, some cases of iodine-induced nephrotoxicity have been reported in patients who did not receive intravascular CM, as a consequence of iodine absorption through mucosae, burned skin or interstitial tissues. Recently, we observed the first case of CI-AKI occurring after an enteroclysis without any direct intravascular injection of CM. Here, we report this case, and review other clinical situations in which renal toxicity has been reported following the non-intravascular use of iodinated compounds.


Keratins as molecular markers of epithelial differentiation: differential expression in crypt epithelium of human palatine tonsils.
The expression of keratins in the stratified squamous nonkeratinizing epithelium lining the surface and the crypts of human palatine tonsils was analyzed by high-resolution gel electrophoresis, immunoblotting, and immunohistochemical techniques. In contrast to the superficial epithelium, which showed a fairly constant keratin composition consisting of the neutral-to-basic keratins K4, K5, K6, and K8 and the acidic keratins K13, K14, K16, and K19, the keratin profiles of tonsillar crypt epithelial cells were found to be more variable, particularly with respect to the expression levels of K4 and K13. These were identical to those of surface epithelium, reduced, or abolished. Since K4 and K13 characterize the mature stage of differentiation in squamous nonkeratinizing epithelia, their decrease is indicative of an incomplete epithelial differentiation. Immunohistochemical analyses confirmed this hypothesis and allowed us, furthermore, to correlate the expression of K13 with the morphologic alterations of tonsillar crypt epithelium in the course of reticulation.


Early complications in bariatric surgery: incidence, diagnosis and treatment.
Bariatric surgery has proven to be the most effective method of treating severe obesity. Nevertheless, the acceptance of bariatric surgery is still questioned. The surgical complications observed in the early postoperative period following surgeries performed to treat severe obesity are similar to those associated with other major surgeries of the gastrointestinal tract. However, given the more frequent occurrence of medical comorbidities, these patients require special attention in the early postoperative follow-up. Early diagnosis and appropriate treatment of these complications are directly associated with a greater probability of control. The medical records of 538 morbidly obese patients who underwent surgical treatment (Roux-en-Y gastric bypass surgery) were reviewed. Ninety-three (17.2%) patients were male and 445 (82.8%) were female. The ages of the patients ranged from 18 to 70 years (average = 46), and their body mass indices ranged from 34.6 to 77 kg/m2. Early complications occurred in 9.6% and were distributed as follows: 2.6% presented bleeding, intestinal obstruction occurred in 1.1%, peritoneal infections occurred in 3.2%, and 2.2% developed abdominal wall infections that required hospitalization. Three (0.5%) patients experienced pulmonary thromboembolism. The mortality rate was 0,55%. The incidence of early complications was low. The diagnosis of these complications was mostly clinical, based on the presence of signs and symptoms. The value of the clinical signs and early treatment, specially in cases of sepsis, were essential to the favorable surgical outcome. The mortality was mainly related to thromboembolism and advanced age, over 65 years.


Backbone and side-chain cleavages in electron detachment dissociation (EDD).
Ab-initio electronic structure methods are used to explore potential energy profiles pertinent to the fragmentations of gas-phase radicals thought to be formed in the new negative-ion mode EDD mass spectroscopic studies of peptides. Barriers to fragmentation as well as the associated overall energy differences are computed for the observed Calpha-C backbone bond cleavage as well as for side-chain loss for a variety of side chains (valine, arginine, glutamic acid, and tyrosine). It is found that Calpha-C bond cleavage is favored over side-chain loss, although loss of a tyrosine side chain may compete with Calpha-C cleavage because the tyrosine radical formed can delocalize its unpaired electron over its aromatic ring. In addition, it is found that fragmentation of the nitrogen-centered radicals formed in EDD results in cleavage to produce so-called a*/x fragments rather than a/x* fragments both because producing the former involves a significantly smaller barrier and is nearly thermoneutral, while cleavage to yield a/x* is significantly endothermic.


Interspecific Phylogenic Relationships within Genus Melilotus Based on Nuclear and Chloroplast DNA.
Melilotus comprises 19 species, while the phylogenetic relationships between species remain unclear. In the present work, three chloroplast genes, rbcL, matK, trnL-F, and one nuclear region, ITS (internal transcribed spacer) belonging to 48 populations of 18 species of Melilotus were sequenced and phylogenetic trees were constructed to study their interspecific relationships. Based on the phylogenetic tree generated in this study using rbcL analysis, the Melilotus genus is clearly monophyletic in the legume family. Both Bayesian and maximum-parsimony approaches were used to analyze the data. The nrDNA ITS provided more informative characteristics (9.8%) than cpDNA (3.0%). Melilotus contains two closely related groups, clade I and clade II. M. spicatus, M. indicus and M. segetalis have a close relationship. M. infestus, M. siculus and M. sulcatus are closely related. The comparing between molecular phylogeny and flower color classification in Melilotus showed that the flower color is not much informative for phylogenetics of this genus.


Evaluating strategies to enhance the anti-tumor immune response to a carbohydrate mimetic peptide vaccine.
Carbohydrate mimetic peptides of tumor associated carbohydrate antigens (TACA) are T-cell-dependent antigens and, therefore, immunization with these surrogates is predicted to overcome the low immunogenicity of carbohydrate antigens. Consistent with this hypothesis, we show that among the potential immune cells involved, peptide immunization led to an increase in T-cell populations. While peptide mimetics may also function as TLR binding ligands, we did not observe evidence of involvement of NK cells. Examining tumor challenged animals, we observed that peptide immunization and not tumor cells rendered IL-12 responsiveness to T-cells, as T-cells from peptide-immunized mice produced IFN-gamma upon stimulation with IL-12. Cyclophosphamide administration enhanced the anti-tumor efficacy of the vaccine, which was achieved by enhancing T-cell responses with no effect on NK cell population. Prophylactic immunization of mice with a DNA construct encoding carbohydrate mimetic peptides indicated a specific role for the mimotope vaccine in anti-tumor immune responses. These data suggest a role for both CD4(+) and CD8(+) T-cells induced by mimotopes of TACA in protective immunity against tumor cells.


Reconstruction of soft tissue defect after maxillectomy of ameloblastic carcinoma with submental island flap: a case report and literature review.
Ameloblastic carcinoma (AC) is an extremely rare malignant odontogenic tumor. The mean age of occurrence for all 141 AC cases analyzed in our systematic review study was 43.59±19.51 years. Males were more affected than females, and the mandible was predominantly affected compared with the maxilla. The main clinical manifestation was a painful or painless swelling with ulceration and radiographic features usually displayed as mixed cystic or solid changes. Surgical resection was the first recommended method of management. Fourteen cases had cervical lymph node spread, 19 had distant metastasis (most commonly in the lung), and 33 had recurrence. We present a rare case of AC involving the maxillary region. Locally extensive surgical resection was carried out. Ablative defects after maxillectomy resulted in the communication of oral cavity and nasal cavity/maxillary antrum and would bring about difficulties in mastication, deglutition, and speech. A submental island flap was applied to close the oronasal and oroantral fistula. The flap and the wounds healed well, with excellent outcomes in terms of appearance, the function of speech, and swallowing on follow up. The submental island flap provides a relatively thin, easy-to-harvest, and well-vascularized tissue, which makes it a reliable option in soft tissue reconstruction of the oral and maxillofacial region.


SIK2 represses AKT/GSK3β/β-catenin signaling and suppresses gastric cancer by inhibiting autophagic degradation of protein phosphatases.
Salt-inducible kinase 2 (SIK2) is an important regulator in various intracellular signaling pathways related to apoptosis, tumorigenesis and metastasis. However, the involvement of SIK2 in gastric tumorigenesis and the functional linkage with gastric cancer (GC) progression remain to be defined. Here, we report that SIK2 was significantly downregulated in human GC tissues, and reduced SIK2 expression was associated with poor prognosis of patients. Overexpression of SIK2 suppressed the migration and invasion of GC cells, whereas knockdown of SIK2 enhanced cell migratory and invasive capability as well as metastatic potential. These changes in the malignant phenotype resulted from the ability of SIK2 to suppress epithelial-mesenchymal transition via inhibition of AKT/GSK3β/β-catenin signaling. The inhibitory effect of SIK2 on AKT/GSK3β/β-catenin signaling was mediated primarily through inactivation of AKT, due to its enhanced dephosphorylation by the upregulated protein phosphatases PHLPP2 and PP2A. The upregulation of PHLPP2 and PP2A was attributable to SIK2 phosphorylation and activation of mTORC1, which inhibited autophagic degradation of these two phosphatases. These results suggest that SIK2 acts as a tumor suppressor in GC and may serve as a novel prognostic biomarker and therapeutic target for this tumor.


Pulmonary phosphatidic acid phosphatase and lipid phosphate phosphohydrolase.
The lung contains two distinct forms of phosphatidic acid phosphatase (PAP). PAP1 is a cytosolic enzyme that is activated through fatty acid-induced translocation to the endoplasmic reticulum, where it converts phosphatidic acid (PA) to diacylglycerol (DAG) for the biosynthesis of phospholipids and neutral lipids. PAP1 is Mg(2+) dependent and sulfhydryl reagent sensitive. PAP2 is a six-transmembrane-domain integral protein localized to the plasma membrane. Because PAP2 degrades sphingosine-1-phosphate (S1P) and ceramide-1-phosphate in addition to PA and lyso-PA, it has been renamed lipid phosphate phosphohydrolase (LPP). LPP is Mg(2+) independent and sulfhydryl reagent insensitive. This review describes LPP isoforms found in the lung and their location in signaling platforms (rafts/caveolae). Pulmonary LPPs likely function in the phospholipase D pathway, thereby controlling surfactant secretion. Through lowering the levels of lyso-PA and S1P, which serve as agonists for endothelial differentiation gene receptors, LPPs regulate cell division, differentiation, apoptosis, and mobility. LPP activity could also influence transdifferentiation of alveolar type II to type I cells. It is considered likely that these lipid phosphohydrolases have critical roles in lung morphogenesis and in acute lung injury and repair.


Total synthesis of (-)-morphine.
We have developed an efficient total synthesis of (-)-morphine in 5% overall yield with the longest linear sequence consisting of 17 steps from 2-cyclohexen-1-one. The cyclohexenol unit was prepared by means of an enzymatic resolution and a Suzuki-Miyaura coupling as key steps. Construction of the morphinan core features an intramolecular aldol reaction and an intramolecular 1,6-addition. Furthermore, mild deprotection conditions to remove the 2,4-dinitrobenzenesulfonyl (DNs) group enabled the facile construction of the morphinan skeleton. We have also established an efficient synthetic route to a cyclohexenol unit containing an N-methyl-DNs-amide moiety.


Reframing social cognition: Relational versus representational mentalizing.
The most dominant theory of human social cognition, the theory of mind hypothesis, emphasizes our ability to infer the mental states of others. After having represented the mental states of another person, however, we can also have an idea of how well our thinking aligns with theirs, and our sensitivity to this alignment may guide the flow of our social interactions. Here, we focus on the distinction between "mindreading" (inferring another's mental representation) and detecting the extent to which a represented mental state of another person is matching or mismatching with our own (mental conflict monitoring). We propose a reframing for mentalizing data of the past 40 years in terms of mental conflict monitoring rather than mental representation. Via a systematic review of 51 false belief neuroimaging studies, we argue that key brain regions implicated in false belief designs (namely, temporoparietal junction areas) may methodologically be tied to mental conflict rather than to mental representation. Patterns of false belief data suggests that autism may be tied to a subtle issue with monitoring mental conflict combined with intact mental representation, rather than to lacking mental representation abilities or "mindblindness" altogether. The consequences of this view for the larger social-cognitive domain are explored, including for perspective taking, moral judgments, and understanding irony and humor. This provides a potential shift in perspective for psychological science, its neuroscientific bases, and related disciplines: Throughout life, an adequate sensitivity to how others think differently (relational mentalizing) may be more fundamental to navigating the social world than inferring which thoughts others have (representational mentalizing). (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Values of radiological examinations for the diagnosis and prognosis of invasive bronchial-pulmonary aspergillosis in critically ill patients with chronic obstructive pulmonary diseases.
The important role of radiological examinations of invasive pulmonary aspergillosis (IPA) in patients with neutropenia has been well studied; however, little is known about IPA in critically ill chronic obstructive pulmonary disease (COPD) patients. To evaluate the value of radiological examinations in the diagnosis and prognosis of invasive bronchial-pulmonary aspergillosis (IBPA) in critically ill COPD patients. We included 61 critically ill COPD patients in the intensive care unit (ICU) in a retrospective, single-center cohort study. All of the patients were classified as IBPA group (n = 21) or non-IBPA group (n = 40). The chest computed tomography (CT) image analysis showed that the IBPA group had the highest percent of patchiness (76.2%), followed by multiple nodules (33.3%), angio-invasive patterns (including halo sign, wedge consolidation and air-crescent sign/cavity with a relatively low percent of 19%, 19% and 28.5%, respectively), and the multiple nodules that were distributed along the airway provided the most specific image, with the highest specificity of 92.5%. Compared to the survivors in the IBPA group, non-surviving patients had a higher percent of large consolidation (0% vs. 45.5%, P = .035). When the new effusions appeared on a chest x-ray (CXR), the creatinine (140.4 μmol/L vs. 64.0 μmol/L, P = .010) and PaO2 /FiO2 (188 mm Hg vs. 222 mm Hg, P = .034) rate deteriorated. Multiple nodules that were distributed along with broncho-vascular bundles were relatively common and specific in critically ill COPD patients with IBPA. Deteriorated CXR combined with specific laboratory examinations, even when appropriate antibiotics were used, could indicate a diagnosis of IBPA. Large consolidations might be considered as poor prognostic indicators.


Clinical outcomes and low-dose levocarnitine supplementation in psychiatric inpatients with documented hypocarnitinemia: a retrospective chart review.
Metabolic encephalopathy is one of the crucial manifestations of carnitine deficiency. In psychiatric patients, low serum carnitine levels may result from chronic valproate therapy. Despite the widespread use of valproate in psychiatry, neither carnitine deficiency nor supplementation has been studied in a psychiatric population. To describe clinical outcomes in hospitalized psychiatric patients with documented hypocarnitinemia who were receiving oral levocarnitine supplementation. Retrospective chart review. In 38 patients with hypocarnitinemia, a low-dose oral levocarnitine supplementation, in association with comprehensive psychiatric therapy, did not result in any adverse psychiatric or medical outcomes, and was associated with overall improved behavioral, cognitive, and motor functioning. Initially all patients had some degree of cognitive impairment, but after correction of carnitine serum levels, scores on the Mini-Mental State Examination (MMSE) improved in most of the patients (mean improvement 5.5 points, P <0.0001), and normalized in 11 cases. This allowed a correction of the diagnosis in 8 of 14 patients who had initially been diagnosed with dementia. African-American patients achieved significantly lower serum carnitine levels and MMSE scores than Caucasian patients with comparable therapy. We hypothesize that correction of carnitine depletion, either by levocarnitine supplementation or by valproate dose reduction, may enhance recovery from hypocarnitinemia-associated encephalopathy in psychiatric patients. Our findings also suggest that ethnic traits may affect carnitine bioavailability as well as cognitive outcomes in this clinical context. Further studies of carnitine metabolism and supplementation in psychiatric patients are warranted.


Bioequivalence, dose-proportionality, and pharmacokinetics of naltrexone after oral administration.
Healthy male volunteers (N = 24) participated in a four-way crossover study to compare the rate and extent of absorption of naltrexone after administration of 50 mg tablets as 50, 100, and 200 mg doses and a 10 mg/ml reference syrup. A high-performance liquid chromatographic method was employed to measure naltrexone and 6-beta-naltrexol in plasma and urine. Compared to the syrup, the 50 mg tablets were absorbed more slowly but equally well. There was excellent linearity between the administered dose and the area under the plasma concentration-time profile, as well as total urinary recovery of both drug and metabolite. The mean half-lives for naltrexone and beta-naltrexol were approximately 4 and 12 hours, respectively. The fraction of drug reaching the systemic circulation was estimated to be 5% of the administered dose because of extensive first-pass metabolism. Less than 1% of the dose was excreted in the urine as naltrexone after 48 hours, while 25% was recovered as unconjugated beta-naltrexol. The renal clearance of naltrexone and beta-naltrexol was approximately 127 ml/min and 283 ml/min, respectively. The total systemic clearance for naltrexone was approximately 94 L/hr.


Loss of atrial signal detection with increasing sensitivity settings: a software problem and its practical solution.
A logic error in the software of Cosmos II results in apparent malsensing of atrial signals at high rather than low sensitivity settings. The paradoxical function was found in 54 out of 87 units tested (= 62%) if the atrial sensitivity was increased and in 54 out of 87 units tested (= 62%) if the atrial sensitivity was increased and the ventricular refractory period was lengthened beyond critical limits that could be defined individually. The problem inherent in both unipolar (66%) and bipolar systems (54%) is attributed to a summation of a physiological signal and internal noise, which has to be detected at the atrial level within a specific timing window to disable atrial sensing for the next pacing cycle. The malfunction virtually disappears if the ventricular refractory period does not exceed 210 msec. It is recommended, therefore, that Cosmos II pacemakers be left at their nominal ventricular refractory value (200 msec).


[The immunogenetic approach and the prinicples of forming an organized collective].
The authors examine the mechanisms of connection between a great complex of human histocompatibility antigens and cellular and humoral factors of immunity that makes it possible to get the clearer idea about the reasons of individual susceptibility or, on the contrary, human stability to various diseases. Immunogenetic criteria cited in the article give the possibility to individualize the primary prophylaxis of illness.


Deviation from Archie's law in partially saturated porous media: Wetting film versus disconnectedness of the conducting phase.
We experimentally study the electrical transport in partially water-saturated pore network. The porous medium under investigation is a Fontainebleau sandstone, characterized by x-ray tomography. We show the existence of two electrical conductivity regimes. At high water saturation, the electric resistivity follows a well-known Archie law. Below a water saturation S_{w} approximately 0.2 , a strong negative deviation from this Archie law is observed. We attribute this transition to the existence of "a thick liquid film," assuring the ionic conduction in the low saturation regime. A numerical simulation is proposed to confirm this scenario. Two possible protocols are used to distribute the brine phase in the pore network of a three-dimensional microtomography image. The first one is based on a minimization of the interfacial energy. The second takes into account a quasistatic capillary displacement. The classical random-walk algorithm is used to compute the electric conductivity at various water saturations. Without the "thick film," both of the two fluid-placing protocols show a disconnectedness transition of the brine phase when S_{w}<0.2 . Adding this "film" to solid surface, the electrical continuity is maintained. The bending down trend is correctly reproduced, showing that in this range, the electric response cannot be described by a power law as usual.


Genotypic heterogeneity of Flavobacterium group IIb and Flavobacterium breve demonstrated by DNA-DNA hybridization.
DNA-DNA hybridization studies on 42 stains presumptively identified as members of Flavobacterium group IIb and Flavobacterium breve indicated pronounced genotypic heterogeneity within these taxa. Three large groups highly related to the type strains of F. gleum, F. indologenes and F. breve respectively, and eight small groups were found. The group containing the type strain of F. breve was phenotypically indistinguishable from another genomic group, and these two groups were significantly separated from the other flavobacteria studied. The other nine genomic groups, representing Flavobacterium group IIb, could not with certainty be differentiated from each other by phenotypic characteristics, and there is no evidence indicating that these genomic groups differ from each other with respect to pathogenicity or ecology. Thus, it is suggested that for the time being the name "Flavobacterium group IIb" rather than specific epithets continue to be used for these bacteria.


Inter-observer agreement of computed tomography and magnetic resonance imaging on gross tumor volume delineation of intrahepatic cholangiocarcinoma: an initial study.
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver tumor, and local radiotherapy has a positive effect on patients with an unresectable tumor. Accurate delineation of gross tumor volume (GTV) is crucial to improve the efficacy of radiotherapy. The purpose of this article was to evaluate the consistency of CT, diffusion weighted imaging (DWI) and Gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced MRI on GTV delineation of ICC. Fourteen patients with ICC underwent CT (Plain and Portal, CT scans before and 70 s after the injection of Omnipaque, respectively), DWI, and Gd-EOB-DTPA-enhanced MRI (EOB 70 s and EOB 15 min, mDIXON scans at 70 s and 15 min after the injection of Gd-EOB-DTPA, respectively) examinations before radiotherapy. Volumes of GTV delineation on CT and MRI images were recorded. Dice similarity coefficient (DSC) was calculated to evaluate the spatial overlap. Tumor volume on DWI and EOB 15 min were larger than that on EOB 70 s significantly (both P=0.004). DSC of DWI was significantly larger than that of other CT and MRI sequences (all P≤0.002). DSC of EOB 15 min tended to be larger than that of other CT sequences and EOB 70 s, however, without significances (all P>0.005). Significant correlation was found between DSC and tumor volume (R=0.35, P=0.003). DWI had significantly higher agreement on GTV delineation of ICC. GTV delineations of ICC on Gd-EOB-DTPA-enhanced MRI showed excellent inter-observer agreement. Fusion of CT and MRI images should be considered to improve the accuracy of GTV delineation.


Public health agencies' use of social media for communication during pandemics: a scoping review of the literature.
Public health agencies (PHAs) have increasingly incorporated social media into their communication mix during successive pandemics in the 21st century. However, the quality, timing, and accuracy of their health messages have varied significantly, resulting in mixed outcomes for communication, audience engagement, and pandemic management. This study aimed to identify factors influencing the effectiveness of pandemic-related health messages shared by PHAs on social media and to report their impact on public engagement as documented in the literature. A scoping literature review was conducted following a predefined protocol. An electronic search of 7 relevant databases and 5 grey literature repositories yielded 9,714 papers published between January 2003 and November 2022. Seventy-three papers were deemed eligible and selected for review. The results underscored the insufficiency of social media guidance policies for PHAs. Six themes were identified: message source, message topic, message style, message timing, content credibility and reliability, and message recipient profile. These themes encompassed 20 variables that could inform PHAs' social media public health communication during pandemics. Additionally, the findings revealed potential interconnectedness among the variables, and this study concluded by proposing a conceptual model that expands upon existing theoretical foundations for developing and evaluating pandemic-related health messaging.


Improved detection of infection with SARS-CoV-2 Omicron variants of concern in healthcare workers by a second-generation rapid antigen test.
The results from this study demonstrate the usefulness of a second-generation rapid antigen test for early detection of infection with the SARS-CoV-2 Omicron variant of concern (VoC) and reveal a higher sensitivity to detect immune escape Omicron VoCs compared to a first-generation rapid antigen test (89.4% vs 83.7%) in the high-risk group of healthcare workers.


A multi-method approach toward de novo glycan characterization: a Man-5 case study.
Regulatory agencies' expectations for biotherapeutic approval are becoming more stringent with regard to product characterization, where minor species as low as 0.1% of a given profile are typically identified. The mission of this manuscript is to demonstrate a multi-method approach toward de novo glycan characterization and quantitation, including minor species at or approaching the 0.1% benchmark. Recently, unexpected isomers of the Man(5)GlcNAc(2) (M(5)) were reported (Prien JM, Ashline DJ, Lapadula AJ, Zhang H, Reinhold VN. 2009. The high mannose glycans from bovine ribonuclease B isomer characterization by ion trap mass spectrometry (MS). J Am Soc Mass Spectrom. 20:539-556). In the current study, quantitative analysis of these isomers found in commercial M(5) standard demonstrated that they are in low abundance (<1% of the total) and therefore an exemplary "litmus test" for minor species characterization. A simple workflow devised around three core well-established analytical procedures: (1) fluorescence derivatization; (2) online rapid resolution reversed-phase separation coupled with negative-mode sequential mass spectrometry (RRRP-(-)-MS(n)); and (3) permethylation derivatization with nanospray sequential mass spectrometry (NSI-MS(n)) provides comprehensive glycan structural determination. All methods have limitations; however, a multi-method workflow is an at-line stopgap/solution which mitigates each method's individual shortcoming(s) providing greater opportunity for more comprehensive characterization. This manuscript is the first to demonstrate quantitative chromatographic separation of the M(5) isomers and the use of a commercially available stable isotope variant of 2-aminobenzoic acid to detect and chromatographically resolve multiple M(5) isomers in bovine ribonuclease B. With this multi-method approach, we have the capabilities to comprehensively characterize a biotherapeutic's glycan array in a de novo manner, including structural isomers at >/=0.1% of the total chromatographic peak area.


Neutrophil degranulation response to 2 hours of exercise in a 30 degrees C environment.
Evidence supports an interaction between neuro-endocrine responses to exercise and immune responses to exercise. We hypothesized that prolonged exercise in the heat would evoke a greater stress hormone response and a greater decrease in neutrophil degranulation [lipopolysaccharide (LPS)-stimulated elastase release] than when the same exercise was performed in thermoneutral conditions. In counterbalanced order and separated by 7 d, 13 male cyclists cycled for 2 h at 62 +/- 3% VO2max (mean +/- SEM), with ad libitum water intake, on one occasion with heat (HOT: 30.3 degrees C, 76% RH) and on another occasion without ( 20.4 degrees C, 60% RH). Venous blood samples were collected at pre-, post-, and 2 h post-exercise. Exercising HR, rating of perceived exertion, rectal temperature, corrected body mass loss, and plasma cortisol at post- and 2 h post-exercise were greater during HOT. A marked neutrophilia was evident at post- and 2 h post-exercise with no difference between trials. LPS-stimulated elastase release per neutrophil decreased post-exercise with no difference between trials (pre-exercise: HOT 189 +/- 20 and CONTROL 210 +/- 32; post-exercise: HOT 127 +/- 18 and CONTROL 136 +/- 29 fg x cell(-1)). There was no effect of exercise or trial on neutrophil CD11b expression (neutrophil activation index) or band cell percentage (neutrophil maturity index). Prolonged exercise results in a decrease in neutrophil degranulation that is unaffected by performing the exercise in hot conditions despite the increase in physiological stress. Additionally, these data suggest that the decrease in neutrophil degranulation after prolonged exercise is not associated with a change in neutrophil activation or maturity as previously suggested.


Surgical aortic valvuloplasty using the Cavitron Ultrasonic Surgical Aspirator: an invasive hemodynamic follow-up study.
Valve repair and calcium debridement in patients with calcific aortic stenosis, using the Cavitron Ultrasonic Surgical Aspirator (CUSA), results in a reduction in the aortic valve gradient while potentially avoiding long-term problems inherent to prosthetic valves. Invasive followup data in these patients has not previously been reported. Ten patients in whom CUSA debridement was performed underwent cardiac catheterization prior to and 8.0 +/- 2.5 months following the procedure. Compared to baseline, the aortic valve area significantly increased from 0.75 +/- 0.2 to 1.1 +/- 0.3 cm2 (p = 0.009) and the mean gradient was significantly reduced from 54 +/- 21 to 27 +/- 21 mmHg (p = 0.02) at followup. No significant change was noted in cardiac output, ejection fraction, left ventricular end systolic or diastolic volumes or left ventricular end diastolic pressure. However, 6 patients were found to have at least one grade worsening of aortic regurgitation. The development of increased aortic insufficiency in many patients after CUSA aortic valve debridement will likely limit this procedure's clinical utility.


Early gastric carcinoma associated with amyloidosis: a case report.
We have experienced a case of early gastric carcinoma associated with amyloidosis. The patient was a 63-year-old woman diagnosed as having early gastric cancer type 0 Ila at the anterior wall on the greater curvature of the antrum, and multiple polypoid lesions on the antrum to the body of the stomach. We performed total gastrectomy, and rho-Roux-en-Y reconstruction. The tumor lesion was recognized at the anterior wall of the prepylorus, and the multiple polypoid lesions which were composed of amyloid masses were recognized on the whole stomach. The histological findings of the biopsy specimens from the rectum and the skin showed no amyloid-deposit. The urine examination was negative for a Bence-Jones protein reaction. This was a rare case of early gastric carcinoma associated with stomach amyloidosis, apparently confined to the stomach.


Hydration-dependent conformational states of hemoglobin. Equilibrium and kinetic behavior.
The equilibrium and kinetics of methemoglobin conversion to hemichrome induced by dehydration were investigated by visible absorption spectroscopy. Below about 0.20 g water per g hemoglobin only hemichrome was present in the sample; above this value, an increasing proportion of methemoglobin appeared with the increase in hydration. The transition between the two derivatives showed a time-dependent biphasic behavior and was observed to be reversible. The rates obtained for the transition of methemoglobin to hemichrome were 0.31 and 1.93 min-1 and for hemichrome to methemoglobin 0.05 and 0.47 min-1. We suggest that hemichrome is a reversible conformational state of hemoglobin and that the two rates observed for the transition between the two derivatives reflect the alpha- and beta-chains of hemoglobin.


How does a CC double bond cleave in the gas phase? Fragmentation of protonated ketotifen in mass spectrometry.
In the literature, it is reported that the protonated ketotifen mainly undergoes CC double bond cleavage in electrospray ionization tandem mass spectrometry (ESI-MS/MS); however, there is no explanation on the mechanism of this fragmentation reaction. Therefore, we carried out a combined experimental and theoretical study on this interesting fragmentation reaction. The fragmentation of protonated ketotifen (m/z 310) always generated a dominant fragment ion at m/z 96 in different electrospray ionization mass spectrometers (ion trap, triple quadrupole and linear trap quadrupole (LTQ)-orbitrap). The mechanism of the generation of this product ion (m/z 96) through the CC double bond cleavage was proposed to be a sequential hydrogen migration process (including proton transfer, continuous two-step 1,2-hydride transfer and ion-neutral complex-mediated hydride transfer). This mechanism was supported by density functional theory (DFT) calculations and a deuterium labeling experiment. DFT calculations also showed that the formation of the product ion m/z 96 was most favorable in terms of energy. This study provides a reasonable explanation for the fragmentation of protonated ketotifen in ESI-MS/MS, and the fragmentation mechanism is suitable to explain other CC double bond cleavage reactions in mass spectrometry. Copyright © 2016 John Wiley & Sons, Ltd.


STAT3 genotypic variation and cellular STAT3 activation and colon leukocyte recruitment in pediatric Crohn disease.
Genotypic variation in signal transducer and activator of transcription 3 (STAT3) increases risk for inflammatory bowel disease (IBD), and STAT3-dependent inflammatory networks are induced in the colon in these patients. We hypothesized that STAT3 "A" risk allele carriage would be associated with increased cellular STAT3 activation and colon leukocyte recruitment. Colonic expression of genes regulating STAT3 signaling and leukocyte recruitment and function was measured in pediatric patients with Crohn disease (CD) stratified by STAT3 genotype. The frequency of colonic pSTAT3* and CXCR2* neutrophils was determined using immunohistochemistry. STAT3 tyrosine phosphorylation (pSTAT3) was measured in circulating leukocytes by flow cytometry, and mechanisms regulating STAT3 activation were tested in IBD Epstein-Barr virus (EBV)-transformed lymphocytes (EBL). Colonic expression of interleukin 6 (IL-6), the STAT3 target gene SOCS3, the neutrophil chemoattractants IL-8, CXCL1, and CXCL3, and the neutrophil products S100A8, S100A9, and S100A12 were increased in patients carrying the STAT3 "A" risk allele. The frequency of neutrophils expressing the cognate receptor for IL-8, CXCR2, was increased in colonic biopsies from patients carrying the risk allele, and the frequency of pSTAT3* or CXCR2* neutrophils correlated with histologic severity. The frequency of CD4 lymphocytes and granulocytes expressing pSTAT3 was increased in patients carrying the STAT3 "A" risk allele. EBLs from patients carrying the STAT3 "A" risk allele exhibited increased basal and IL-6-stimulated STAT3 tyrosine phosphorylation, increased transcription of STAT3 and SOCS3 after IL-6 stimulation, and increased membrane localization of the IL-6 receptor, GP130, and Janus-associated kinase 2. The STAT3 "A" risk allele is associated with increased cellular STAT3 activation and upregulation of pathways that promote recruitment of CXCR2* neutrophils to the gut.


Causal explanations for common somatic symptoms among women and men.
The purpose of this study was to examine categories of causal attributions assessed by women and men regarding common somatic symptoms. A questionnaire was sent out to a randomly selected sample of 1,500 persons followed by a screening of respondents with symptom experience. To identify groups of individuals considering different causes or causal categories as important, separate cluster analyses were made of ratings for neck/shoulder problems and sore/upset stomach. The results showed similarities between assessed causal categories for the two types of symptoms and that women in this sample were overrepresented, particularly in considering psychological explanations for their symptoms, whereas the men were overrepresented in not considering any of the causes as particularly important. This was discussed in terms of illness severity and an association between psychological and somatic distress in people's experience, such as stress and total workload, and in their subsequent explanatory models suggesting differences in beliefs about a connection between body and mind.


High Rate and Low-Temperature Stable Lithium Metal Batteries Enabled by Lithiophilic 3D Cu-CuSn Porous Framework.
Lithium (Li) metal is regarded as the "Holy Grail" of anodes for high-energy rechargeable lithium batteries by virtue of its ultrahigh theoretical specific capacity and the lowest redox potential. However, the Li dendrite impedes the practical application of Li metal anodes. Herein, lithiophilic three-dimensional Cu-CuSn porous framework (3D Cu-CuSn) was fabricated by a vapor phase dealloying strategy via the difference in saturated vapor pressure between different metals and the Kirkendall effect. CuSn alloy sites were converted into LiSn alloy sites through the molten Li infusion method, and composite Li metal anodes (3D Cu-LiSn-Li) are achieved. Alloyed tin, as the bridge between the porous copper substrate and metallic Li, plays a critical role in optimizing Li nucleation and enhancing the fast lithium migration kinetics. This work demonstrates that lithiophilic binary copper alloys are an effective way to achieve room-temperature high rate performance and satisfied low-temperature cycling stability for Li metal batteries.


Broadband reflection holograms in dichromated gelatin.
The spectral response of broadband reflection holograms in dichromated gelatin is studied; conditions for obtaining 100-nm bandwidth and 80% diffraction efficiency holograms are given. The structure of these holograms is discussed, and the scanning electron microscope is used to investigate fringe-spacing variations.