[Idiopathic Nephrotic Syndrome: recommendations of the Nephrology Branch of the Chilean Society of Pediatrics. Part One].
Idiopathic nephrotic syndrome is the most common glomerular disease in childhood, affecting 1 to 3 per 100,000 children under the age of 16. It most commonly occurs in ages between 2 and 10. Its cause is unknown and its histology corresponds to minimal change disease in 90% of cases, or focal segmental glomerulosclerosis. 80 to 90% of cases respond to steroids (steroid-sensitive nephrotic syndrome) with good prognosis and long-term preservation of renal function over time. 70% of patients with SSNS have one or more relapses in their evolution, and of these, 50% behave as frequent relapsing or steroid-dependent, a group that concentrate the risk of steroid toxicity. Patients with steroid-resistant nephrotic syndrome have a poor prognosis and 50% of them evolve to end-stage renal disease. The goal of therapy is to induce and maintain remission of the disease, reducing the risk secondary to proteinuria while minimizing the adverse effects of treatments, especially with prolonged use of corticosteroids. This paper is the result of the collaborative effort of the Nephrology Branch of the Chilean Society of Pediatrics with aims at helping pediatricians and pediatric nephrologists to treat pediatric SNI. In this first part, recommendations of steroid-sensitive nephrotic syndrome are discussed.


Age Drives the Differences in Dietary Supplement Use in Endurance Athletes: A Cross-Sectional Analysis of Cyclists, Runners, and Triathletes.
Most athletes use dietary supplements (DS) to improve health and performance beyond what can be achieved through diet. Improvements in health and exercise performance through the use of DS are especially attractive to older athletes (OA) challenged with age-related declines. However, there are few DS shown to improve endurance performance, and the prevalence of DS in OA are unknown. Two-hundred cyclists, runners, and triathletes (females = 108; age = 39.4 ± 13.5) completed a questionnaire regarding the prevalence and type of DS currently used, in addition to variables associated with using DS such as motivation and sources of information. Overall, 78.0% of athletes reported current DS use. OA used more DS (Total DS = 4.3 ± 3.0) than younger athletes (2.7 ± 1.8, p < 0.001), with ages 40-49 and 50-59 using more DS than ages 18-29 and 30-39 (p < 0.05). The majority of athletes (53.8%) used ≥ 3 DS. Age was the only significant predictor of total DS use (p = 0.002); OA used ≥ 3 DS more than younger (p < 0.001). Specifically, more athletes 40-49 (67.5%) and 50-59 (76.2%) used ≥ 3 DS compared to 18-29 (33.3%, p = 0.003). More OA used electrolytes (p = 0.005), probiotics (p = 0.045), melatonin (p = 0.004), and vitamin D (p = 0.016) than younger athletes. Motivations to use DS were related to age and were supplement specific. Sources of DS information varied by sex more than age. Age is a significant determining factor for DS use in a sample of cyclists, runners, and triathletes. The prevalence and trends of DS warrant further investigation into the benefits and risks of DS to develop safe, targeted, and age-specific DS strategies on a recreative competitive level.Supplemental data for this article is available online at https://doi.org/10.1080/19390211.2022.2056670 .


Performance and relationship of four different agricultural drought indices for drought monitoring in China's mainland using remote sensing data.
Increasing frequency and intensity of extreme drought events have harmed the environment, ecosystem, and agricultural productivity. However, the characteristics of agricultural drought in China have not been well understood. The remote sensing (RS) based gridded monthly precipitation, soil moisture, land surface temperature (LST), and normalized difference vegetation index (NDVI) datasets over 1982-2018 were utilized to derive standardized precipitation index (SPI), standardized soil moisture index (SSI), multivariate standardized drought index (MSDI), and vegetation health index (VHI). The variation patterns and trends of SPI, SSI, and MSDI at the 1-, 3-, and 6-month timescales against monthly VHI anomaly were compared to identify the best agricultural drought index in China. The drought variations in the four sub-regions (northwest, north, Qinghai-Tibet area, and south area) were also investigated. The results showed that: (1) Temporal patterns of VHI anomaly were similar to relative soil moisture and slightly different from precipitation. The spatial patterns of MSDI matched with VHI the best than SPI and SSI. (2) All three indices showed positive correlations with VHI at the three timescales. The highest correlation coefficients (r) between MSDI and VHI ranged from 0.25 to 0.67, 0.22 to 0.78, 0.23 to 0.69, and 0.19 to 0.74 in northwest China, north China, Qinghai-Tibet Plateau, and south China, respectively. (3) The connections between monthly VHI and the three drought indices were weaker at the 1-month timescale (0.16 < r < 0.25) than the 3-month (0.39 < r < 0.78) and 6-month (0.26 < r < 0.68) timescales. (4) The VHI significantly increased in most of China except north China. Overall, MSDI showed better performance for monitoring agricultural drought in China's mainland.


Antimicrobial activity of E-4441, a representative azetidine quinolone.
E-4441 is a third-generation difluoroquinolone characterized by the presence in position 7 of an azetidine ring, disubstituted in position 3 by amine and methyl groups. E-4322 is another difluoroquinolone which differs from the former in having a 3-acetidinol substitution in position 7. E-4441 shows satisfactory levels of activity, both in vitro and in vivo, its activity against G(+) aerobic bacteria and anaerobic bacteria being generally notable.


Effect of the taxonomic group of fungi and type of substrate on the antioxidant activity of a solid-state fermentation system.
The enzymatic and non-enzymatic antioxidant activities of a solid-state fermentation system (SSFS) employing six basidiomycete and four ascomycete fungi on orange peel have been evaluated. Class comparisons revealed highly significant effect of fungal group on the antioxidant activity. Peroxidase activity appeared only in the basidiomycete fungi (particularly Pleurotus columbinus, Ganoderma resinaceum, and Pleurotus floridanus) whereas catalase activity appeared in the two fungal groups in favor of the ascomycetes (particularly Paecilomyces variotii and Aspergillus fumigatus). Maximal peroxidase and minimal catalase activities were found at moderate phenolic content, with extreme phenolic levels leading to low peroxidase activity but high catalase activity. Production of the non-enzymatic antioxidants (phenolics, flavonoids, reducing power, and DPPH scavenging) was in favor of the ascomycetes, which showed great native ability to synthesize flavonoids and also to release flavonoids from orange peel. The basidiomycete fungi, which have limited native ability to produce phenolics, had high ability to consume orange peel phenolics. By contrast, the ascomycete fungi exhibited great native ability for production of phenolics and low ability to consume exogenous phenolics.


A stochastic dynamical model for nosocomial infections with co-circulation of sensitive and resistant bacterial strains.
Nosocomial infections (hospital-acquired) has been an important public health problem, which may make those patients with infections or involved visitors and hospital personnel at higher risk of worse clinical outcomes or infection, and then consume more healthcare resources. Taking into account the stochasticity of the death and discharge rate of patients staying in hospitals, in this paper, we propose a stochastic dynamical model describing the transmission of nosocomial pathogens among patients admitted for hospital stays. The stochastic terms of the model are incorporated to capture the randomness arising from death and discharge processes of patients. Firstly, a sufficient condition is established for the stochastic extinction of disease. It shows that introducing randomness in the model will result in lower potential of nosocomial outbreaks. Further, we establish a threshold criterion on the existence of stationary distribution and ergodicity for any positive solution of the model. Particularly, the spectral radius form of stochastic threshold value is calculated in the special case. Moreover, the numerical simulations are conducted to both validate the theoretical results and investigate the effect of prevention and control strategies on the prevalence of nosocomial infection. We show that enhancing hygiene, targeting colonized and infected patients, improving antibiotic treatment accuracy, shortening treatment periods are all crucial factors to contain nosocomial infections.


Calcaneal broadband ultrasound attenuation predicts physical capability: EPIC-Norfolk prospective population-based study.
Calcaneal ultrasound (broadband ultrasound attenuation - BUA), a marker of bone strength, may predict future physical capability and thus provide a strategy to identify individuals at risk of age-related deterioration of health. This study aims to determine if BUA can predict future physical capability among middle-aged and older adults. Summary performance scores (SPS), an objective quantification of physical capability, were devised using participants' measures of standing balance, gait speed and timed chair rises. Associations between BUA and SPS, measured at least six years apart, were investigated using univariable and multivariate sex-specific linear and logistic regression, adjusting for confounders. 5893 participants were included. In men and women, for every five points lower BUA, there was a 0.2-point decrease in SPS. In women, BUA less than one standard deviation below the mean was associated with low physical capability (defined as SPS 3-6); fully adjusted odds ratio (OR) (95 % confidence interval (CI)) 1.35 (1.01-1.84). No association existed among men; OR (95 % CI) 0.84 (0.59-1.19). Significant risk factors for low physical capability in men with baseline low BUA were: older age [OR 5.77]; high BMI [OR 2.85]; lower social class [OR 1.59]; low physical activity [OR 1.64]. Risk factors among women were: older age [OR 5.54]; high BMI [OR 2.08]; lower education [OR 1.42], low physical activity [OR 1.27]; steroid use [OR 2.05]; and stroke [OR 2.74]. BUA may predict future physical capability in older adults. With further validation, BUA could stratify individuals at risk of deterioration in physical health.


Determinants of repeated blood donation among new and experienced blood donors.
The maintenance of a safe level of blood supply is provided by a small number of volunteers, and their retention is difficult. The aim of this study was to identify factors predicting repeated blood donation among experienced and new donors. A random sample of 2,231 donors (2,070 experienced and 161 new) completed a questionnaire assessing psychosocial factors as defined by the most prominent social cognitive theories. Six months later, an objective measure of frequency of registrations to give blood was obtained from the database of the local official agency for blood donation. Logistic regression analysis indicated that for experienced donors, the predictors were intention, perceived control, anticipated regret, moral norm, age, and frequency of blood donation in the past. For new donors, intention and age were the only determinants of behavior. Important differences in the determinants of intention were also noted between experienced and new donors. In summary, the results of this study support the idea that distinct promotion strategies should be adopted to increase repeated blood donation among experienced versus new donors.


New protein farnesyltransferase inhibitors in the 3-arylthiophene 2-carboxylic acid series: diversification of the aryl moiety by solid-phase synthesis.
A new synthetic pathway was devised to reach tetrasubstituted 3-arylthiophene 2-carboxylic acids in a three-step solid-phase synthesis. This very efficient methodology provided more than 20 new compounds that were evaluated for their ability to inhibit protein farnesyltransferase from different species as well as Trypanosoma brucei and Plasmodium falciparum proliferation.


A comparison by magnetic circular dichroism of compound X and compound II of horseradish peroxidase.
The chlorite product of horseradish peroxidase, compound X, is shown by magnetic circular dichroism (MCD) spectroscopy in the temperature range 1.6-50 K to have a very similar haem structure to compound II under the same conditions (pH 10.7). Both are concluded to contain the Fe(IV) = 0 group. The MCD spectrum also detects an unusual species, absorbing at wavelengths between 600 and 750 nm, that has magnetic properties different from those of the ferryl haem group. It is suggested that this is a species at the same oxidation level as ferryl haem but with the porphyrin ring having suffered a one-electron oxidation, i.e. [Fe(III) P.+].


A paper-based device for the colorimetric determination of ammonia and carbon dioxide using thiomalic acid and maltol functionalized silver nanoparticles: application to the enzymatic determination of urea in saliva and blood.
A colorimetric assay was developed which has the capability of determining urea in biological samples. It is an origami paper-based sensor consisting of silver nanoparticles that were synthesized by using two different capping agents: thiomalic acid and maltol. The function of the assay relied on hydrolysis of urea to ammonia and carbon dioxide in the presence of urease. The products interacted with nanoparticles which caused aggregation. Interestingly, thiomalic acid capped with silver nanoparticles were selective to ammonia, and the other nanoparticles synthesized by maltol responded to carbon dioxide. These interactions turned the color of nanoparticles from yellow to brown and red, respectively. The resulting colorations were captured by a floatable scanner. A routine image analysis software was utilized to provide the response of the assays. The method was applied to individually determine ammonia, carbon dioxide, and urea. The linear range was 0.06 mg.dL-1-170.0 mg.dL-1 for ammonia, 0.08 mg.dL-1-220.0 mg.dL-1 for carbon dioxide, and 0.5 mg.dL-1-200.0 mg.dL-1 for urea. The respective limits of detection were 0.03 mg.dL-1, 0.06 mg.dL-1, and 0.18 mg.dL-1. No interferences were found in the detremination of urea. The method demonstrates a reliable performance for determination of urea in both saliva and blood samples. Graphical Abstract Schematic representation of paper based colorimetric sensor based on silver nanoparticles for both qualitative and quantitative analyses of urea in biological samples.


Elimination of Theileria buffeli infections from cattle by concurrent treatment with buparvaquone and primaquine phosphate.
Attempts (some successful) were made to eliminate Theileria buffeli infections from 23 naturally or experimentally infected, splenectomised calves. The anti-theilerial hydroxynaphthoquinone derivative buparvaquone was used either alone or in combination with primaquine phosphate. After treatment the calves were monitored for infection for up to 26 weeks. Blood films were examined for piroplasms and serum antibody levels were measured using an immunofluorescence technique. Buparvaquone alone failed to eliminate infections. Infections were eliminated from 11 of 16 calves treated twice with buparvaquone and three or six times with primaquine phosphate. Theilerial parasites were not subsequently seen in these 11 calves nor were antibodies detected beyond the eighth week after treatment.


The effects of plyometric jump training on jump and sport-specific performances in prepubertal female swimmers.
Dry land-training (e.g., plyometric jump training) can be a useful mean to improve swimming performance. This study examined the effects of an 8-week plyometric jump training (PJT) program on jump and sport-specific performances in prepubertal female swimmers. Twenty-two girls were randomly assigned to either a plyometric jump training group (PJTG; n = 12, age: 10.01 ± 0.57 years, maturity-offset = -1.50 ± 0.50, body mass = 36.39 ± 6.32 kg, body height = 146.90 ± 7.62 cm, body mass index = 16.50 ± 1.73 kg/m2) or an active control (CG; n = 10, age: 10.50 ± 0.28 years, maturity-offset = -1.34 ± 0.51, body mass = 38.41 ± 9.42 kg, body height = 143.60 ± 5.05 cm, body mass index = 18.48 ± 3.77 kg/m2). Pre- and post-training, tests were conducted for the assessment of muscle power (e.g., countermovement-jump [CMJ], standing-long-jump [SLJ]). Sport-specific-performances were tested using the timed 25 and 50-m front crawl with a diving-start, timed 25-m front crawl without push-off from the wall (25-m WP), and a timed 25-m kick without push-off from the wall (25-m KWP). Findings showed a significant main effect of time for the CMJ (d = 0.78), the SLJ (d = 0.91), 25-m front crawl test (d = 2.5), and the 25-m-KWP (d = 1.38) test. Significant group × time interactions were found for CMJ, SLJ, 25-m front crawl, 50-m front crawl, 25-m KWP, and 25-m WP test (d = 0.29-1.63) in favor of PJTG (d = 1.34-3.50). No significant pre-post changes were found for CG (p > 0.05). In sum, PJT is effective in improving muscle power and sport-specific performances in prepubertal swimmers. Therefore, PJT should be included from an early start into the regular training program of swimmers.


Yersinia enterocolitica: a significant 'new' pathogen.
It thrives in the cold, defies conventional culture methods, does not respond to most antibiotics, and may mimic other disorders in its manifestations. Fortunately, most cases of yersinial enterocolitis are mild and self-limiting, but infection can be life-threatening, especially in neonates or when immunologic defenses are impaired. Clinical and laboratory diagnostic criteria and epidemiologic clues are described.


MEF2B Instructs Germinal Center Development and Acts as an Oncogene in B Cell Lymphomagenesis.
The gene encoding the MEF2B transcription factor is mutated in germinal center (GC)-derived B cell lymphomas, but its role in GC development and lymphomagenesis is unknown. We demonstrate that Mef2b deletion reduces GC formation in mice and identify MEF2B transcriptional targets in GC, with roles in cell proliferation, apoptosis, GC confinement, and differentiation. The most common lymphoma-associated MEF2B mutant (MEF2BD83V) is hypomorphic, yet escapes binding and negative regulation by components of the HUCA complex and class IIa HDACs. Mef2bD83V expression in mice leads to GC enlargement and lymphoma development, a phenotype that becomes fully penetrant in combination with BCL2 de-regulation, an event associated with human MEF2B mutations. These results identify MEF2B as a critical GC regulator and a driver oncogene in lymphomagenesis.


Relationship between the intracellular cyclic adenosine 3':5'-monophosphate level of tumor cells and their sensitivity to killing by antibody and complement.
Metabolic inhibitors which have been shown to increase the sensitivity of the guinea pig hepatoma, line 10, to antibody-guinea pig complement killing were tested for their effect on the intracellular cyclic adenosine 3':5'-monophosphate (cAMP) level of the line 10 cells. It was found that cells rendered sensitive to antibody-guinea pig complement killing following drug treatment showed a decrease in their intracellular cAMP levels. Increased susceptibility to lysis was always associated with decreased intracellular cAMP levels. Optimal doses of certain inhibitors effectively increased the sensitivity of the cells to complement-dependent lysis and decreased the intracellular cAMP levels. Other drugs which did not increase sensitivity of the cells to lysis also failed to decrease the intracellular cAMP levels. No experimental conditions were found in which intracellular cAMP levels were decreased without an increase in the susceptibility of the cells to antibody-guinea pig complement killing.


Effect of Fluconazole and Itraconazole on the Pharmacokinetics of Erdafitinib in Healthy Adults: A Randomized, Open-Label, Drug-Drug Interaction Study.
Erdafitinib, an oral selective pan-fibroblast growth factor receptor (FGFR) kinase inhibitor, is primarily metabolized by cytochrome P450 (CYP) 2C9 and 3A4. The aim of this phase 1 study was to assess the pharmacokinetics and safety of erdafitinib in healthy participants when coadministered with fluconazole (moderate CYP2C9 and CYP3A inhibitor), and itraconazole (a strong CYP3A4 and P-glycoprotein inhibitor). The effect of CYP2C9 genotype variants (*1/*1, *1/*2, *1/*3) on the pharmacokinetics of erdafitinib was also investigated. In this open-label, parallel-group, single-center study, eligible healthy adults were randomized by CYP2C9 genotype to receive Treatment A (single oral dose of erdafitinib 4 mg) on day 1, Treatment B (fluconazole 400 mg/day orally) on days 1-11, or Treatment C (itraconazole 200 mg/day orally) on days 1-11. Healthy adults randomized to Treatment B and C received a single oral 4-mg dose of erdafitinib on day 5. The pharmacokinetic parameters, including mean maximum plasma concentration (Cmax), area under the curve (AUC) from time 0 to 168 h (AUC168h), AUC from time 0 to the last quantifiable concentration (AUClast), and AUC from time 0 to infinity (AUC∞) were calculated from individual plasma concentration-time data using standard non-compartmental methods. Coadministration of erdafitinib with fluconazole increased Cmax of erdafitinib by approximately 21%, AUC168h by 38%, AUClast by 49%, and AUC∞ by 48% while coadministration with itraconazole resulted in no change in erdafitinib Cmax and increased AUC168h by 20%, AUClast by 33% and AUC∞ by 34%. Erdafitinib exposure was comparable between participants with CYP2C9 *1/*2 or *1/*3 and with wild-type CYP2C9 genotype. The ratio of total amount of erdafitinib excreted in the urine (inhibited to non-inhibited) was 1.09, the ratio of total amount of excreted metabolite M6 was 1.21, and the ratio of the metabolite to parent ratio in the urine was 1.11, when coadministration of erdafitinib with itraconazole was compared with single-dose erdafitinib. Treatment-emergent adverse events (TEAEs) were generally Grade 1 or 2 in severity; the most commonly reported TEAE was headache. No safety concerns were identified with single-dose erdafitinib when administered alone and in combination with fluconazole or itraconazole in healthy adults. Coadministration of fluconazole or itraconazole or other moderate/strong CYP2C9 or CYP3A4 inhibitors may increase exposure to erdafitinib in healthy adults and thus may warrant erdafitinib dose reduction or use of alternative concomitant medications with no or minimal CYP2C9 or CYP3A4 inhibition potential. ClinicalTrials.gov identifier number: NCT03135106.


Biosurfactants as microbial bioactive compounds in microbial enhanced oil recovery.
Fossil fuels such as petroleum resources continue to be a significant fraction of the energy portfolio. Oil sludge or slops have become an unavoidable waste in the petroleum industries, and their improper disposal measures have led to environmental pollution. Various conventional and traditional practices for disposal and recovery are practiced, but the efficiency of MEOR has led to more promising and efficient ways to recover oil from oil reservoirs and waste sludges. Among the microbial bioactives, biosurfactants are the key players in the whole process. Although, MEOR using biosurfactants has been largely practiced for recovering oil from oil reservoirs, microbial metabolites are also proving to be effective in recovering oil from the waste oily sludges generated as a part of the petroleum production cycle. MEOR stands out as a economically sound alternative over other conventional methods that require large capital investment, heavy energy consumption and varying recovery efficiency. This review describes the scope of MEOR to be useful in reducing and reusing the waste oily sludge accumulation that when untreated causes environmental pollution, allowing sustainable use of natural resources. However, lack of reproducibility at field scale, large scale production of bioactive compounds are the major reasons leading to its incompatibility. The review aims to address the gaps and possible strategies to help speed up the efficiency by thoroughly focusing on the biosurfactant mediated MEOR process dynamics and use of various non-renewable substrates as measure of waste utilization for the production of metabolites. The molecular makeup of these significant molecules after extracting them from the contaminated niche will help discover microbial diversity. Furthermore, the limitations to this biosurfactant assisted MEOR can be solved by using genomic and high throughput approaches to execute an economical implementation at field scale level.


Vata dynamics with special reference to cardiac disorders - A cross-disciplinary approach.
Vata is one of the fundamental patho-physiological entities with unique and dynamic properties. All actions inside the body, whether voluntary or involuntary, are governed by Vayu. Actions involved during natural physiological calls or urges, are involuntary, but partially under voluntary control. Classical texts from Ayurveda state that such natural urges (NU) should be strictly attended without disturbing their natural flow. Some urges can be intentionally or inadvertently initiated (Udiran) or suppressed (Dhaaran), redirecting the normal flow of Vayu, leaving scopes for severe morbidities in the heart causing cardiovascular disorders (CVD). Since Vata has unique attribute of Vega (locomotion) that moves in a specific direction, its intensities can be quantified with the help of modern techniques. Few studies have objectively evaluated the intensities of NU like belching, sneezing, expulsion of flatus, etc. during normalcy, which may help us to determine their altered activity during morbidity. In spite of such studies, their relevance to CVD is inadequately explored. Hence, this article addresses details of such NU that lead to CVD alone, from classical texts of Ayurveda, conventional medicines and technology that quantify their intensities. Citing research articles from various journals using keywords were done to understand their mechanism along with their intensities. It was found that objective estimation of few NU was performed extensively whereas some had limitations. Theories from the classical texts confirm that physiological NU, if allowed to flow freely without any impedance, assures good health. It would certainly benefit the mankind if their pathologic state is timely detected so as to prevent disease progression in CVD.


Multifocal electroretinogram in retinal vein occlusion.
To determine the effects of retinal vein occlusion (RVO) on multifocal electroretinogram (MF-ERG) parameters, to correlate MF-ERG and standard electroretinogram (ERG) and to correlate MF-ERG with findings of optical coherence tomography (OCT) in cases of RVO. Both eyes of 50 patients with RVO and 50 eyes of 25 normal subjects were examined using MF-ERG, standard ERG, fluorescein angiography and OCT. The latency in millisecond (ms) and response density in nanovolt (nv/degenerations) were measured for each of four quadrant areas and central area. OCT was used to measure the foveal retinal thickness. Fluorescein angiography was used to measure retinal ischemia. Central retinal vein occlusion (CRVO) markedly affected all parameters of MF-ERG. In pathological quadrants in branch retinal vein occlusion, the response densities of MF-ERG were decreased and latencies of p-wave were prolonged. The MF-ERG responses obtained from eyes with RVO were significantly different (P > 0.05) from derived from the fellow eyes. The amplitude of MF-ERG were abnormal in 40 eyes and implicit times were delayed in 48 eyes compared with normal subjects. While 30 Hz flicker implicit were abnormal in only 24 eyes with RVO. Implicit times were prolonged in eyes with macular ischemia than in eyes without ischemia. There were significant correlation between foveal retinal thickness measured by OCT and P response density MF-ERG in cases of retinal vein occlusion. MF-ERG is more susceptible than standard ERG to eye changes of RVO due to the multiple frequencies of stimulation used to record MF-ERG response. MF-ERG could be sensitive indicator of underlying disease affecting the retinal in eyes with RVO. MF-ERG is useful for detecting local retinal dysfunction in patients with RVO and sensitive to morphological changes and functional disorders induced by RVO.


Carbonic anhydrase VI activity in saliva and biofilm can predict early childhood caries: A preliminary study.
This study aimed to investigate whether carbonic anhydrase VI activity (CA VIACT ), pH, and buffering capacity (BC) in saliva and biofilm could predict the number of lesion occurrence and early childhood caries (ECC). A cross-sectional study was performed in a sample of 44 children aged 4 to 5 years who were examined regarding their caries status (dmfs + active white spot lesions-WSL) and allocated into two groups: ECC and caries-free (CF). Saliva and biofilm were collected to determine pH, BC, and CA VIACT . Data were analyzed using the Student t test, and multiple linear regression and logistic regression analyses followed by the ROC curve. Children with ECC exhibited lower pH and BC in saliva and a higher CA VIACT in both saliva and biofilm. Only saliva pH could predict the dmfs + active WSL. In biofilm, if CA VIACT is increased by one pixel/µg, 0.85 ± 0.28 increase is expected in the number of active WSL. Salivary pH and CA VIACT in saliva and biofilm had the power to predict ECC occurrence. Changes in saliva pH and CA VIACT in biofilm predicted the number of lesion occurrence. Furthermore, CA VIACT in both saliva and biofilm can predict propensity for ECC.


Burden of disease induced by public overexposure to solar ultraviolet radiation (SUVR) at the national and subnational levels in Iran, 2005-2019.
Estimating the burden of diseases induced by overexposure to solar ultraviolet radiation (SUVR) can help to prioritize environmental health interventions. The age-sex specific and cause-specific mortality and disability-adjusted life years (DALYs) attributable to overexposure to SUVR at the national and subnational levels in Iran, 2005-2019 were estimated. The burden of disease induced by overexposure to SUVR was quantified in four steps as follows: (1) estimating exposure to SUVR, (2) estimating total incidences and deaths of target causes, (3) assessing population attributable fractions of the target causes for the SUVR, and (4) calculating the attributable burden of disease. The attributable DALYs, deaths, age-standardized DALY rate, and age-standardized death rate at the national level were determined to be respectively 21896, 252, 42.59, and 0.56 in 2005 and were respectively changed to 28665, 377, 38.76, and 0.53 in 2019. The contributions of causes in the attributable DALYs at the national level were different by year and sex and for both sexes in 2019 were as follows: 46.15% for cataract, 20.36% for malignant skin melanoma, 16.07% for sunburn, 12.41% for squamous-cell carcinoma, and 5.01% for the other five causes. The contributions of population growth, population ageing, risk exposure, and risk-deleted DALY rate in the temporal variations of the attributable burden of disease in the country were +20.73%, +20.68%, +2.01%, and -12.51%. The highest and lowest provincial attributable age-standardized DALY rates in 2019 were observed in Fars (46.8) and Ardebil (32.7), respectively. The burden of disease induced by exposure to SUVR caused relatively low geographical inequality in health status in Iran. Due to increasing trends of the SUVR as well as the attributable burden of disease, the preventive interventions against the SUVR overexposure should be considered in the public health action plan all across the country.


Quantitative analysis of two COVID-19 antiviral agents, favipiravir and remdesivir, in spiked human plasma using spectrophotometric methods; greenness evaluation.
Favipiravir and remdesivir have been included in the COVID-19 treatment guidelines panel of several countries. The main objective of the current work is to develop the first validated green spectrophotometric methods for the determination of favipiravir and remdesivir in spiked human plasma. The UV absorption spectra of favipiravir and remdesivir have shown some overlap, making simultaneous determination difficult. Due to the considerable overlap, two ratio spectra manipulating spectrophotometric methods, namely, ratio difference and the first derivative of ratio spectra, enabled the determination of favipiravir and remdesivir in their pure forms and spiked plasma. The ratio spectra of favipiravir and remdesivir were derived by dividing the spectra of each drug by the suitable spectrum of another drug as a divisor to get the ratio spectra. Favipiravir was determined by calculating the difference between 222 and 256 nm of the derived ratio spectra, while calculating the difference between 247 and 271 nm of the derived ratio spectra enabled the determination of remdesivir. Moreover, the ratio spectra of every drug were transformed to the first order derivative using ∆λ = 4 and a scaling factor of 100. The first-order derivative amplitude values at 228 and 251.20 nm enabled the determination of favipiravir and remdesivir, respectively. Regarding the pharmacokinetic profile of favipiravir (Cmax 4.43 µg/mL) and remdesivir (Cmax 3027 ng/mL), the proposed methods have been successfully applied to the spectrophotometric determination of favipiravir and remdesivir in plasma matrix. Additionally, the greenness of the described methods was evaluated using three metrics systems: the national environmental method index, the analytical eco-scale, and the analytical greenness metric. The results demonstrated that the described models were in accordance with the environmental characteristics.


Psychometric properties and validation of the Brief NORSCI safety perceptions and climate inventory in the Norwegian waste management industry.
A valid, standardized tool for assessing workplace safety can help organizations and employers to detect potential safety risks. This is crucial to improve safety and protect employees and production against accidents and injuries. As no such tool has so far been developed for the waste management industry, this study aimed to establish the psychometric properties and the concurrent validity of the 11-item Brief Norwegian Safety Climate Inventory (Brief NORSCI). A cross-sectional questionnaire study was conducted with 543 workers from the formal Norwegian waste management industry. Exploratory and confirmatory factor analyses showed that the Brief NORSCI exhibited good psychometric properties. Replicating previous validation studies of the inventory, the findings suggested a three-factor structure reflecting Individual intention and motivation, Management's prioritization of safety, and Safety routines. The three first-order factors of the inventory could be combined in a composite second-order safety climate factor. Both the overall composite score and the three subscales correlated in the expected directions with measures of job characteristics (i.e., job demands and resources), leadership, social climate, and severe accidents, thus indicating high concurrent validity. This study supported the validity and reliability of the Brief NORSCI as an assessment tool to measure both individual safety perceptions and group level safety climate among waste management workers. The findings suggest that application of the Brief NORSCI as a safety assessment tool may contribute to the development of a stronger safety profile among organizations and companies in waste management.


Evidence-based approaches for promoting gender equity in global mental health research: Study protocol for social network analysis of researchers in Nepal.
There are increasing efforts for capacity building of researchers in low- and middle-income countries (LMIC) to foster local ability to conduct high quality research. However, female researchers remain underrepresented in scientific communities, particularly in LMIC where they have limited networking and mentorship opportunities. This protocol is for a Social Network Analysis (SNA) to evaluate if gender-sensitive, need-based capacity building can improve researchers' networking and mentorship opportunities in Nepal. The conceptual framework is informed by Social Cognitive Career Theory. Cross-sectional and longitudinal SNA are used to a) assess individual researchers' network characteristics and their association with academic productivity; and b) examine if the association of network characteristics and academic productivity is mediated by self-efficacy and outcome expectations. Recruitment is designed to include early-career and senior researchers conducting mental health research, as well as students interested in pursuing a career in mental health research. The network characteristics will be mapped for approximately 150 researchers in working in Nepal. SNA characteristics in the network (individual density, homophily, and centrality) will be compared with academic productivity (total peer reviewed publications, h-index), including mediation effects via self-efficacy and outcome expectations. Ultimately, this study will generate information to design more evidence-based strategies for capacity building of a gender-equitable research workforce in global mental health.


Comprehensive Gas-Phase Peptide Ion Structure Studies Using Ion Mobility Techniques: Part 2. Gas-Phase Hydrogen/Deuterium Exchange for Ion Population Estimation.
Gas-phase hydrogen/deuterium exchange (HDX) using D2O reagent and collision cross-section (CCS) measurements are utilized to monitor the ion conformers of the model peptide acetyl-PAAAAKAAAAKAAAAKAAAAK. The measurements are carried out on a home-built ion mobility instrument coupled to a linear ion trap mass spectrometer containing electron transfer dissociation (ETD) capabilities. ETD is utilized to obtain per-residue deuterium uptake data for select ion conformers, and a new algorithm is presented for interpreting the HDX data. Using molecular dynamics (MD) production data and a hydrogen accessibility scoring (HAS)-number of effective collisions (NEC) model, hypothetical HDX behavior is attributed to various in-silico candidate (CCS match) structures. The HAS-NEC model is applied to all candidate structures, and non-negative linear regression is employed to determine structure contributions resulting in the best match to deuterium uptake. The accuracy of the HAS-NEC model is tested with the comparison of predicted and experimental isotopic envelopes for several of the observed c-ions. It is proposed that gas-phase HDX can be utilized effectively as a second criterion (after CCS matching) for filtering suitable MD candidate structures. In this study, the second step of structure elucidation, 13 nominal structures were selected (from a pool of 300 candidate structures) and each with a population contribution proposed for these ions. Graphical Abstract .


Two Electrocardiographic Aberrations Important for All Caring for Patients to Know about.
Two electrocardiographic (ECG) aberrations encountered daily in ECG interpretation/overreading, which appear to be either unknown or ignored, by all caring for patients, are described herein: the 1st is the transient increase in the amplitude of QRS complexes in the right precordial ECG leads, leading to the erroneous diagnosis of left ventricular hypertrophy, often encountered in patients with episodes of supraventricular tachycardia, rapid sinus tachycardia, and atrial fibrillation; the 2nd is the spurious ST-segment elevations in lateral and/or inferior ECG leads in patients with right bundle branch block, interpreted by the automated ECG diagnostic algorithms as due to "acute myocardial infarction," "ischemic injury," "pericarditis," and "early repolarization," in the absence of such pathologies or electrophysiological explanations.


Surgical outcome of elephant-trunk anastomosis between the left carotid and subclavian arteries in aortic arch repair including the postoperative physical status of the left arm.
We studied the outcome of our modified aortic arch replacement procedure in which the distal end of the graft is anastomosed between the left common carotid artery and the left subclavian artery including the postoperative physical status of the left arm in comparison with the conventional technique. We assessed the surgical outcome of 26 patients who underwent our new technique and 11 patients who underwent the conventional one. Postoperative clinical symptoms and physical status of the left arm were also evaluated. No operative deaths were observed in the new technique group and one operative death was observed in the conventional group (9.1%). No significant differences between the two groups in postoperative clinical symptoms and the physical status of the left arm were observed. Our "distal anastomosis to the proximal level of the left subclavian artery" technique made aortic arch replacement easier and steadier with a satisfactory surgical outcome in comparison with the conventional method. The postoperative clinical symptoms and physical status of the left arm in the new technique group were identical to those in the conventional group.


A contribution to the knowledge of leaf-mining Phyllocnistis Zeller, 1848 associated with Baccharis (Asteraceae), with description of two new species from Peru (Lepidoptera: Gracillariidae).
We provide new information on Neotropical Phyllocnistis Zeller (Gracillariidae) associated with Baccharis (Asteraceae) in the Andes region. Two new species are described, P. canta Cerdea Farfn, n. sp. and P. elongata Cerdea Farfn, n. sp., from the western slopes of the Andes of Peru between 2,000 and 3,000 m elevation, both associated with Baccharis latifolia (R.P.) Pers. The type locality of P. baccharidis Hering is confirmed; immature stages were found at 1,300 m feeding on Baccharis tucumanensis Hook. Arn. in Quebrada las Higueras (Tucumn, Argentina). Four new locality records for P. furcata Vargas Cerdea are provided, extending its distribution by 450 km to the north of the type locality.


MicroRNA-16 suppresses the activation of inflammatory macrophages in atherosclerosis by targeting PDCD4.
Programmed cell death 4 (PDCD4) is involved in a number of bioprocesses, such as apoptosis and inflammation. However, its regulatory mechanisms in atherosclerosis remain unclear. In this study, we investigated the role and mechanisms of action of PDCD4 in high-fat diet-induced atherosclerosis in mice and in foam cells (characteristic pathological cells in atherosclerotic lesions) derived from ox-LDL-stimulated macrophages. MicroRNA (miR)-16 was predicted to bind PDCD4 by bioinformatics analysis. In the mice with atherosclerosis and in the foam cells, PDCD4 protein expression (but not the mRNA expression) was enhanced, while that of miR‑16 was reduced. Transfection with miR‑16 mimic decreased the activity of a luciferase reporter containing the 3' untranslated region (3'UTR) of PDCD4 in the macrophage-derived foam cells. Conversely, treatment with miR‑16 inhibitor enhanced the luciferase activity. However, by introducing mutations in the predicted binding site located in the 3'UTR of PDCD4, the miR‑16 mimic and inhibitor were unable to alter the level of PDCD4, suggesting that miR‑16 is a direct negative regulator of PDCD4 in atherosclerosis. Furthermore, transfection wtih miR‑16 mimic and siRNA targeting PDCD4 suppressed the secretion and mRNA expression of pro-inflammatory factors, such as interleukin (IL)-6 and tumor necrosis factor-α (TNF‑α), whereas it enhanced the secretion and mRNA expression of the anti-inflammatory factor, IL-10. Treatment with miR‑16 inhibitor exerted the opposite effects. In addition, the phosphorylation of p38 and extracellular signal-regulated kinase (ERK), and nuclear factor-κB (NF-κB) expression were altered by miR‑16. In conclusion, our data demonstrate that the targeting of PDCD4 by miR‑16 may suppress the activation of inflammatory macrophages though mitogen-activated protein kinase (MAPK) and NF-κB signaling in atherosclerosis; thus, PDCD4 may prove to be a potential therapeutic target in the treatment of atherosclerosis.


Perspectives on medical assistance in dying amongst persons with traumatic spinal cord injury: a qualitative study.
Qualitative. To explore the perspectives of persons living with chronic (>5 y) traumatic spinal cord injuries (tSCI) concerning medical assistance in dying (MAID). Saskatchewan, Canada. Qualitative exploratory using an interpretative description methodology. Individual semi-structured interviews were held with online video conferencing. Interviews were analyzed using codebook thematic analysis. Ten persons with a chronic (>5 y) tSCI participated (seven males, three females; age 20s-50s; spinal cord level C2-T10). Participants expressed support for persons living with SCI having access to MAID, specifically in the context of preserving autonomy and respecting equality when compared with able-bodied individuals. However, some were concerned about the implications of access to MAID solely based on the diagnosis of a SCI. Participants also emphasized the variability in the initial personal response to injury and expressed concern about MAID being immediately available after injury. They explained the significance and necessity of reflecting on the injury in what can be a lengthy process of adjustment and acceptance. Participants also discussed the importance of hope and highlighted the irreplaceable value of peer support in shaping hope throughout rehabilitation and the need for compassionate, comprehensive, and continuous care to facilitate reintegration and support independence. Access to MAID provides a greater range of choices for individuals with tSCI but could increase deaths occurring before optimal adaptation and adjustment. The involvement of inter-professional teams, mental health specialists and peers is important to frame hope and understand the potential of a fulfilling life with a tSCI.


Gait dynamics in mouse models of Parkinson's disease and Huntington's disease.
Gait is impaired in patients with Parkinson's disease (PD) and Huntington's disease (HD), but gait dynamics in mouse models of PD and HD have not been described. Here we quantified temporal and spatial indices of gait dynamics in a mouse model of PD and a mouse model of HD. Gait indices were obtained in C57BL/6J mice treated with the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg/day for 3 days) for PD, the mitochondrial toxin 3-nitropropionic acid (3NP, 75 mg/kg cumulative dose) for HD, or saline. We applied ventral plane videography to generate digital paw prints from which indices of gait and gait variability were determined. Mice walked on a transparent treadmill belt at a speed of 34 cm/s after treatments. Stride length was significantly shorter in MPTP-treated mice (6.6 +/- 0.1 cm vs. 7.1 +/- 0.1 cm, P < 0.05) and stride frequency was significantly increased (5.4 +/- 0.1 Hz vs. 5.0 +/- 0.1 Hz, P < 0.05) after 3 administrations of MPTP, compared to saline-treated mice. The inability of some mice treated with 3NP to exhibit coordinated gait was due to hind limb failure while forelimb gait dynamics remained intact. Stride-to-stride variability was significantly increased in MPTP-treated and 3NP-treated mice compared to saline-treated mice. To determine if gait disturbances due to MPTP and 3NP, drugs affecting the basal ganglia, were comparable to gait disturbances associated with motor neuron diseases, we also studied gait dynamics in a mouse model of amyotrophic lateral sclerosis (ALS). Gait variability was not increased in the SOD1 G93A transgenic model of ALS compared to wild-type control mice. The distinct characteristics of gait and gait variability in the MPTP model of Parkinson's disease and the 3NP model of Huntington's disease may reflect impairment of specific neural pathways involved.


The effect of lipopolysaccharide on anti-inflammatory and pro-inflammatory cytokines production of human amniotic epithelial cells.
Intrauterine infection is a major cause of immune imbalance at the maternal-fetal interface, which leads to spontaneous abortion, premature rupture of the fetal membranes, and preterm birth. Human amniotic epithelial cells (hAECs) play a fundamental role in the maintenance of pregnancy. We hypothesize that bacteria influence the immunomodulatory effects of hAECs through stimulation of Toll-like receptors (TLRs). Here, we investigated how lipopolysaccharide (LPS) as a bacterial component affects anti-inflammatory and pro-inflammatory cytokines production of hAECs. Human placentas were obtained from six healthy pregnant women and hAECs were isolated. The phenotypic characteristics of hAECs were determined by flow cytometry. The hAECs (4 × 105 cells/ml) were cultured in the presence or absence of LPS (5 μg/ml). The viability of the cells was assessed and culture supernatants of hAECs were collected after 24, 48 and 72 h of incubation. The levels of transforming growth factor-beta1 (TGF-β1), interleukin-4 (IL-4), tumor necrosis factor-alpha (TNF-α), interleukin-17 A (IL-17A), and interferon-gamma (IFN-γ) were measured by ELISA. Our data showed that LPS treatment did not affect the viability of hAECs, while had a stimulatory effect on TGF-β1 production of hAECs (p < 0.001). A significant reduction in IL-4 production of LPS-stimulated hAECs was observed (p < 0.05). LPS enhanced the production of TNF-α and IL-17 A of hAECs (p < 0.05-0.0001). The IFN-γ level was only detectable in two culture supernatants of hAECs, and the level was unchanged after stimulation with LPS. Based on these findings, LPS may play a pivotal role in immune imbalance at the feto-maternal interface through affecting anti-inflammatory and pro-inflammatory cytokines production of hAECs.


Agaric acid induces mitochondrial permeability transition through its interaction with the adenine nucleotide translocase. Its dependence on membrane fluidity.
The effect of agaric acid as inducer of mitochondrial permeability transition was studied. It was found that: (i) agaric acid (AA) promoted efflux of accumulated Ca2+, collapse of transmembrane potential, and mitochondrial swelling; (ii) these effects depend on membrane fluidity; (iii) ADP inhibited the effect of AA on Ca2+ efflux, and (iv) AA blocked binding of the sulfhydryl reagent, eosin-5-maleimide, to the adenine nucleotide translocase. It is proposed that AA induces pore opening through binding of the citrate moiety to the ADP/ATP carrier; this interaction must be stabilized by insertion of the alkyl chain in the lipid milieu of the membrane.


Abdominal aortic aneurysmal and endovascular device infection with iliopsoas abscess caused by Mycobacterium bovis as a complication of intravesical bacillus Calmette-Guérin therapy.
Vascular complications after the intravesical instillation of Bacillus Calmette-Guérin (BCG) therapy are extremely rare. We experienced a case of abdominal aortic aneurysmal infection excluded by a stent graft with an iliopsoas abscess after intravesical instillation of BCG therapy that required reoperation. Five years ago, an 81-year-old man was diagnosed with transitional cell carcinoma of the bladder. After transurethral resection of the bladder tumor and intravesical BCG therapy, a radical cystectomy was performed. Twenty-four months after intravesical BCG therapy, follow-up an abdominal computed tomographic (CT) scan revealed an aortic abdominal aneurysm. Endovascular aneurysm repair was performed, and the aneurysm was excluded postoperatively. Thirty months after the endovascular aneurysm repair (and 54 months after intravesical BCG therapy), a follow-up abdominal CT revealed a low-density area in the right iliopsoas muscle that formed a fistula to the excluded aneurysm. We performed CT-guided iliopsoas abscess drainage and collected yellow pus. Polymerase chain reaction analysis revealed that the pus was positive for Mycobacterium tuberculosis complex. The patient was diagnosed with abdominal aortic aneurysmal infection associated with iliopsoas abscess caused by Mycobacterium bovis, and surgery was performed. We performed an extra-anatomical bypass and removed the stent graft with debridement. When the aneurysmal wall was incised and resected, yellow pus surrounded the stent graft. In addition, a large fistula was present between the right posterolateral aortic aneurysmal wall and the iliopsoas abscess cavity. After the operation, the histopathological examination of excised abdominal aortic aneurysmal wall tissue revealed an epithelioid granuloma with caseous necrosis involving multinucleated giant cells, indicating M tuberculosis complex infection. Although the intravesical instillation of BCG therapy is considered safe, complications resulting from vascular infections can arise in extremely rare cases. The complication described in this case report emphasizes the need to cautiously select treatment for a mycotic aortic aneurysm after intravesical instillation of BCG therapy.


Teaching the pharyngeal flap and sphincter pharyngoplasty: The sticky note method.
To demonstrate a cost-effective, quick, and easily reproducible three-dimensional sticky note model to enhance the understanding and conceptualization of the geometry and steps of the pharyngeal flap and sphincter pharyngoplasty. The method involves making specified incisions and rearrangements of readily available components, including disposable clear plastic cups, yellow and pink sticky notes, and white paper. Once assembly is complete, further incisions and remodeling are performed to simulate a pharyngeal flap or sphincter pharyngoplasty. The cost of the materials to make one model was $0.94. Average construction time was less than 10 min. This three-dimensional model is an efficient, interactive, and simple visual aid to teach surgical trainees the geometry and steps of the pharyngeal flap and sphincter pharyngoplasty.


Experience of the transplant team is an important factor for posttransplant survival in patients with hepatocellular carcinoma undergoing living-donor liver transplantation.
Living-donor liver transplantation (LDLT) is an effective treatment for patients with unresectable hepatocellular carcinoma (HCC). However, it remains controversial whether expanded listing criteria can be used for LDLT. We aimed to review results of LDLT for patients with HCC at our center. Patients with HCC were accepted for LDLT if there was no extrahepatic spread on computed tomography (CT) and positron emission tomography CT scan. Transarterial chemoembolization was performed before LDLT to control the tumors. Sirolimus or everolimus was used as part of the immunosuppressive protocol for all patients. Over the last 6 years, 35 of the 102 (34%) LDLT were performed at our center for HCC. Age (mean +/- SEM) was 55.3 +/- 1.3 years; 28 patients (80%) were men. Eight (23%) had LDLT performed in 2002 or 2003 (period 1), and 27 (77%) in 2004 to 2007 (period 2). Eleven (31%) were within and 23 (69%) were outside the Milan criteria. After 583 +/- 76 days follow-up, nine (25%) died, three of recurrent HCC. Three-year survival was significantly better in period 2 than in period 1 (90% vs 13%; P < .001). Although the 3-year survival for those within Milan criteria was better than those outside Milan criteria, the difference did not reach statistical significance (86% vs 57%; P = .26). Six (17%) had HCC recurrence, of whom five died. We concluded that reasonable medium-term survival can be obtained for patients with HCC. The experience level of the transplant team seemed to be the most important predictor of patient outcome.


Peptide ligands on the PEGylated nanoparticle surface and human serum composition are key factors for the interaction between immune cells and nanoparticles.
The architecture of a nanoparticles' surface formed due to a modification with a ligand and protein corona formation in biofluids is critical for interactions with cells in vivo. Here we studied interactions of immune cells with magnetic nanoparticles (MNPs) covalently modified with polyethylene glycol (PEG) and their counterparts conjugated with peptides: a pH (low) insertion peptide (pHLIP) and cycloRGD as a targeting ligand in human serum. The conjugation of MNPs-PEG with pHLIP, but not with cycloRGD, enhanced the association of these particles with mononuclear phagocytic cells in vitro and in vivo. We did not find a clear difference in protein corona composition between the pHLIP-modified and parental PEGylated nanoparticles. Analysis of the effect of autologous human serum on MNP uptake by monocytes showed that the efficiency of endocytosis varies among healthy donors and depends on intrinsic properties of serum. Nevertheless, using classic blood, coagulation, biochemical tests, and anti-PEG IgG serum level, we failed to identify the cause of the observed interdonor variation. These individual differences should be taken into consideration during testing of nanotherapeutics.


Evidence for parallel explicit and implicit sequence learning systems in older adults.
Some research indicates that explicit learning of a sequence can impair procedural learning, particularly in populations with reduced cognitive capacity. However, these studies usually do not distinguish the effects of explicit processes on procedural learning from their effects on performance. The current study demonstrates that explicit learning affects performance, but not procedural sequence learning, in healthy older adults even when sequences are complex. These findings support capacity-independent theories which propose that procedural and declarative learning operate in parallel.


Neuropsychology of executive functions in patients with focal lesion in the prefrontal cortex: A systematic review.
Executive functions are conceptualized as a set of cognitive processes that coordinate more basic processes for the resolution of complex behaviors. This neuronal substrate is believed to reside in the most anterior part of the brain. A systematic review of the high-impact literature was carried out to investigate what were the main deficits in executive functions after brain injury. It was found that the literature is fundamentally oriented towards the investigation of the ventromedial cortex and its deficits in decision-making and moral reasoning. Research on the dorsolateral cortex and more cognitive functions such as working memory is relegated to a second choice. This review proposes that a correct functioning of the ventromedial cortex is necessary in order to integrate emotional, cognitive and sensory information for an adequate choice in decision making and moral reasoning. It has also been found that the main deficits of working memory in the dorsolateral cortex are more associated with complex and visuospatial tasks. However, an increase in research synthesizing this type of study is necessary to reach more definitive conclusions.


Structure and organization of the gene encoding a mouse mitochondrial stress-70 protein.
We have previously found that an antigenic protein specific for C3H strain mouse (C3H strain-specific antigen, CSA) is identical to peptide-binding protein 74 (PBP74). PBP74/CSA is a novel member of the stress-70 protein family in mitochondria. In this study, mouse genomic clones encoding PBP74/CSA, including the 5'- and 3'-flanking regions of the gene, have been isolated and sequenced. The PBP74/CSA gene contained 17 exons interrupted by 16 introns. Two dimeric repeats of the consensus sequence of the heat-shock element are present in the 5'-flanking region of the PBP74/CSA gene. Moreover, the first intron is interrupted within the amino-terminal leader sequence, the pattern of which is similar to that of cytochrome c1 located in the mitochondria.


Initial clinical experience with remifentanil, a new opioid metabolized by esterases.
Remifentanil is a new, esterase-metabolized opioid for anesthesia. Nonspecific esterases terminate the drug effect, with a context-sensitive half-time which plateaus at 3-4 min. This dose-ranging pilot study was designed to estimate the dose requirement of remifentanil for abolition of the responses to skin incision and intraoperative stimuli, and to determine the speed of recovery. Fifty-one unpremedicated patients took part at two centers. Anesthesia was induced with propofol, 67% nitrous oxide, and vecuronium. Remifentanil was then given (1 microgram/kg, plus an infusion of 0.0125-1.0 micrograms.kg-1.min-1). Responses were defined as: > 15% increase in systolic blood pressure or > 20% increase in heart rate, tearing, sweating, movement, or coughing. Responses to incision or surgery were treated with 0.5 micrograms/kg remifentanil boluses and a 50% increase in infusion rate, which could be done twice. Subsequent responses were treated with propofol or isoflurane. Remifentanil and nitrous oxide administration were terminated after the incision was closed. ED50 for response to skin incision varied between the two study sites (0.020 and 0.087 microgram.kg-1.min-1). ED50 for response to all surgical stimuli was 0.52 microgram.kg-1.min-1. At 0.3 microgram.kg-1.min-1 or more, only 3 of 21 patients required isoflurane. Recovery was not longer in patients receiving larger doses to spontaneous ventilation (2.5-4.6 min), tracheal extubation (4.2-7.0 min), and response to verbal command (3.0-4.6 min). Postoperative pain was reported in most patients (92%) at a median time of 21 min. We conclude that remifentanil was effective and well tolerated as a component of nitrous oxide-opioid-relaxant anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)


The fine structure of spermatogenesis in Hymenolepis diminuta (Cestoda) with a description of the mature spermatozoon.
The processes of spermatogenesis and spermiogenesis in Hymenolepis diminuta were studied by electron microscopy using improved preparative techniques. Spermatogonia (Type A) are characterized by nuclei 3.79 (+/- 0.17) micrometer in diameter, dense cytoplasm packed with free ribosomes and aggregates of mitochondria. After mitoses, certain spermatogonia (Type B) assume syncytial rosettes containing eight nuclei. Primary spermatocytes maintain the rosette syncytium and have large nuclei (4.28 +/- 0.24 micrometer in diameter), smooth endoplasmic reticulum, and polysomes. The secondary spermatocyte is short-lived and is characterized by nuclei (2.0 +/- 0.11 micrometer in diai (2.0 +/- 0.11 micrometer in diameter) and perinuclear membranous lamellae. The syncytial spermatid cluster contains avoid nuclei which condense and elongate to a final diameter of 0.22 +/- 0.04 micrometer. Once elongated, these nuclei become delimited from the syncytium by invaginations of the plasma membrane. During delimitation, cortical peripheral microtubules arise beneath the spermatozoon plasmalemma and a 9 + 1 axoneme extends the length of the mature lance-shaped spermatozoon.


On the mode of action ofClostridium difficile toxin A: anin vitro study.
C. difficile toxin A causes the rounding up and the formation of surface blebs in normal rat intestinal crypt cells (IEC-6). These phenomena, together with the inhibition of DNA synthesis and the cell lysis, could be the mechanisms leading the toxin-treated cells to death.


Probiotics and human lactational mastitis: a scoping review protocol.
The objective of this scoping review is to identify and examine the evidence on probiotic consumption and its effect on human lactational mastitis. Lactational mastitis is a painful, inflammatory condition of the breast tissue commonly occurring among breastfeeding women. It can lead to decreased breastfeeding rates, which then may lead to poorer maternal and newborn outcomes. There is growing interest and research on the use of probiotics to prevent or treat this condition following promising, but equivocal, evidence from studies of probiotics in relation to animals and other human conditions. Eligible studies will include women of any age who are planning a pregnancy, pregnant, breastfeeding, or expressing post-childbirth. There will be no exclusion based on comorbidity, previous history, or current diagnosis or treatment of lactational mastitis. All probiotic species and strains and all dosages, preparations, and timing/scheduling of probiotic administration will be eligible for inclusion. All concepts regarding the use of probiotics and their effect on lactational mastitis will be included, and all types of research will be considered. This scoping review will follow JBI methodology for scoping reviews. Sources of evidence published in English from 2000 to present will be included. The search will include the Cochrane Library, Scopus, Embase, and Emcare, in addition to gray literature. A critical appraisal will be performed, and the results will be presented in the final review. A tabular and accompanying narrative summary of the information will be provided.


Use of lithium hexafluoroisopropoxide as a mild base for Horner-Wadsworth-Emmons olefination of epimerizable aldehydes.
[reaction: see text] The weak base lithium 1,1,1,3,3,3-hexafluoroisopropoxide (LiHFI) is shown to be highly effective as a reagent for intermolecular Horner-Wadsworth-Emmons (HWE) olefination of epimerizable aldehydes with trimethyl phosphonoacetate, affording products with little or no epimerization and notably high E-selectivity.


Tropical paraplegia: a case of transverse myelitis, probably caused by schistosomiasis mansoni.
In tropical regions transverse myelitis may be caused by involvement with schistosoma or the eggs of this organism. Although 200 million people seem to be infected with this disease, involvement of the spinal cord is rare. A case of a 15-year-old boy is described and some literature reviewed.


Ozone pollution in London and Edinburgh: spatiotemporal characteristics, trends, transport and the impact of COVID-19 control measures.
Air pollution remains the most serious environmental health issue in the United Kingdom while also carrying non-trivial economic costs. The COVID-19 lockdown periods reduced anthropogenic emissions and offered unique conditions for air pollution research. This study sources fine-granularity geo-spatial air quality and meteorological data for the capital cities of two UK countries (i.e. England's capital London and Scotland's capital Edinburgh) from the UK Automatic Urban and Rural Network (AURN) spanning 2016-2022 to assess long-term trends in several criteria pollutants (PM10, PM2.5, SO2, NO2, O3, and CO) and the changes in ozone pollution during the pandemic period. Unlike other studies conducted thus far, this research integrates several tools in trend estimation, including the Mann-Kendall test, the Theil-Sen estimator with bootstrap resampling, and the generalized additive model (GAM). Moreover, several investigations, including cluster trajectory analysis, pollution rose plots, and potential source contribution function (PSCF), are also employed to identify potential origin sources for air masses carrying precursors and estimate their contributions to ozone concentrations at receptor sites and downwind areas. The main findings reveal that most of the criteria pollutants show a decreasing trend in both geographies over the seven-year period, except for O3, which presents a significant ascending trend in London and a milder ascending trend in Edinburgh. However, O3 concentrations have significantly decreased during the year 2020 in both urban areas, despite registering sharp increases during the first lockdown period. In turn, these findings indicate on one hand that the O3 generation process is in the VOC-limited regime in both UK urban areas and, on the other hand, confirm previous findings that, when stretching the analysis period, diminishing ozone levels can lead to NOx reduction even in VOC-controlled geographies. Trajectory analysis reveals that northern Europe, particularly Norway and Sweden, is a principal ozone pollution source for Edinburgh, whereas, for London, mainland Europe (i.e., the Benelux countries) is another significant source. The results have important policy implications, revealing that effective and efficient NOx abatement measures spur ozone pollution in the short-term, but the increase can be transient. Moreover, policymakers in London and Edinburgh should consider that both local and transboundary sources contribute to local ozone pollution.


Genome sequencing and annotation of a Campylobacter coli strain isolated from milk with multidrug resistance.
As the most prevalent bacterial cause of human gastroenteritis, food-borne Campylobacter infections pose a serious threat to public health. Whole Genome Sequencing (WGS) is a tool providing quick and inexpensive approaches for analysis of food-borne pathogen epidemics. Here we report the WGS and annotation of a Campylobacter coli strain, FNW20G12, which was isolated from milk in the United States in 1997 and carries multidrug resistance. The draft genome of FNW20G12 (DDBJ/ENA/GenBank accession number LWIH00000000) contains 1, 855,435 bp (GC content 31.4%) with 1902 annotated coding regions, 48 RNAs and resistance to aminoglycoside, beta-lactams, tetracycline, as well as fluoroquinolones. There are very few genome reports of C. coli from dairy products with multidrug resistance. Here the draft genome of FNW20G12, a C. coli strain isolated from raw milk, is presented to aid in the epidemiology study of C. coli antimicrobial resistance and role in foodborne outbreak.


Nuclear type II [3H]estradiol binding site ligands: inhibition of ER-positive and ER-negative cell proliferation and c-Myc and cyclin D1 gene expression.
These studies assessed the effects of 3,4-dihydroxybenzalacetone (ZN-1) and 1-(3,4-dihydroxyphenyl)-2-propanol (ZN-2) on MCF-7 cell proliferation. The compounds blocked [3H]estradiol binding to nuclear type II sites, but did not compete for [3H]estradiol binding to recombinant ERalpha or ERbeta. ZN-1 and ZN-2 inhibited the proliferation of ERalpha and ERbeta positive (MCF-7) and negative (MCF-10A) breast cells, further ruling out direct binding to ER in the mechanism of action of these compounds. Pre-loading type II sites with ZN-1 or ZN-2 reduced [3H]estradiol exchange, strongly suggesting the drugs were binding covalently. ZN-1 treatment resulted in complete occupancy of type II sites and sustained (9 days) inhibition of MCF-7 cell proliferation following its removal from the tissue culture medium. This cell growth inhibition was not due to non-specific toxicity, as the numbers of viable, attached cells per dish (determined by trypan blue dye exclusion) remained constant throughout this 9-day period and eventually reversed by day 19. ZN-2 effects on cell proliferation reversed more rapidly following discontinuation of treatment, a response consistent with the inability of the compound to totally block type II binding. Both ZN-1 and ZN-2 blocked estradiol stimulation of c-Myc and cyclin D1 gene expression in MCF-7 cells, two events that are clearly coupled to cell cycle progression. We suspect this may occur through ZN-1 or ZN-2 modification of nucleosome function and/or chromatin remodeling since nuclear type II sites are localized to a complex of histones H3 and H4 (Shoulars et. al, J Steroid Biochem. Mol. Biol. 96: 19-30, 2005).


A systematic review and meta-analysis on the efficacy and safety of the Baska mask versus other laryngeal mask airways during general anaesthesia.
The Baska mask is a supraglottic airway device used during general anaesthesia that combines features from various other devices. This systematic review aims to compare its efficacy and safety with other laryngeal mask airways. Randomised controlled trials were identified by searching PubMed, Scopus, Web of Science and Cochrane Library. RevMan software was used for meta-analysis, with mean difference and risk ratios calculated for continuous and dichotomous data, respectively, along with a 95% confidence interval. The meta-analysis found that the Baska mask provides a better oropharyngeal seal pressure (mean difference = 7.03; 95% confidence interval = [6.00, 8.07], p < 0.00001) and a higher rate of maximal seal pressure (risk ratio = 18.38; 95% confidence interval = [2.53, 133.47], p = 0.004) compared to other laryngeal mask airways. However, the Baska mask had lower success rates in first-attempt insertion (risk ratio = 0.79; 95% confidence interval = [0.72, 0.86], p < 0.00001) and higher rates of insertion manipulation (risk ratio = 16.64; 95% confidence interval = [5.86, 47.24], p < 0.00001). The Baska mask offers better oropharyngeal seal pressure, but may be more difficult to insert than other laryngeal mask airways, without causing significant delays. The Baska mask appears as safe as other laryngeal mask airways, but larger trials are needed to support these findings.


Diverting loop ileostomy with colonic lavage as an alternative to colectomy for fulminant Clostridioides difficile: a systematic review and meta-analysis.
Surgical consultation is recommended for all patients with fulminant Clostridioides difficile infection (CDI). If surgery is required, total abdominal colectomy (TAC) is most commonly performed. However, diverting loop ileostomy and colonic lavage have been recently developed as a potential colon-sparing approach to fulminant CDI. The aim of this review is to compare TAC and diverting loop ileostomy with colonic lavage for fulminant CDI. Search of MEDLINE, EMBASE, CENTRAL, and PubMed was performed. Articles were eligible for inclusion if they compared TAC and diverting loop ileostomy with colonic lavage. The primary outcome was postoperative mortality, and the secondary outcome was postoperative complications. Quality of included studies was assessed using Newcastle-Ottawa Scale. From 64 relevant citations, 5 studies (4 retrospective cohorts, 1 case series) with 3683 patients were included. Compared to TAC, diverting loop ileostomy with colonic lavage did not significantly reduce overall mortality (RR 1.10, 95% CI 0.60 to 1.99, P = 0.77), rate of reoperation (RR 1.02, 95% CI, 0.63 to 1.63, P = 0.94), or overall postoperative complications (RR 0.51, 95% CI, 0.22 to 1.17, P = 0.11). Rates of colonic preservation with the use of diverting loop ileostomy with colonic lavage ranged from 76% to 100%. There does not appear to be a survival advantage with the use of diverting loop ileostomy with colonic lavage compared to TAC for fulminant CDI. However, diverting loop ileostomy with colonic lavage results in increased rates of colonic preservation, restoration of intestinal continuity, and laparoscopic surgery. This review is limited by the small number of included studies.


Severity of mental illness as a result of multiple childhood adversities: US National Epidemiologic Survey.
To examine patterns of childhood adversity, their long-term consequences and the combined effect of different childhood adversity patterns as predictors of subsequent psychopathology. Secondary analysis of data from the US National Epidemiologic Survey on alcohol and related conditions. Using latent class analysis to identify childhood adversity profiles; and using multinomial logistic regression to validate and further explore these profiles with a range of associated demographic and household characteristics. Finally, confirmatory factor analysis substantiated initial latent class analysis findings by investigating a range of mental health diagnoses. Latent class analysis generated a three-class model of childhood adversity in which 60 % of participants were allocated to a low adversity class; 14 % to a global adversities class (reporting exposures for all the derived latent classes); and 26 % to a domestic emotional and physical abuse class (exposed to a range of childhood adversities). Confirmatory Factor analysis defined an internalising-externalising spectrum to represent lifetime reporting patterns of mental health disorders. Using logistic regression, both adversity groups showed specific gender and race/ethnicity differences, related family discord and increased psychopathology. We identified underlying patterns in the exposure to childhood adversity and associated mental health. These findings are informative in their description of the configuration of adversities, rather than focusing solely on the cumulative aspect of experience. Amelioration of longer-term negative consequences requires early identification of psychopathology risk factors that can inform protective and preventive interventions. This study highlights the utility of screening for childhood adversities when individuals present with symptoms of psychiatric disorders.


Immunoreactive pancreatic secretory trypsin inhibitor in sera from patients with acute ulcerative colitis.
The serum levels of immunoreactive pancreatic secretory trypsin inhibitor (irPSTI) and immunoreactive cationic trypsin (irCT) were measured in 14 patients admitted for severe acute attacks of ulcerative colitis. Patients with acute colitis had significantly higher irPSTI levels in serum (35 micrograms/l) as compared with controls (11.5 micrograms/l), while the serum level of irCT was within normal limits. The normal colonic mucosa recently has been shown to contain irPSTI favoring the theory of an extrapancreatic origin of the increased serum levels of irPSTI in patients with severe active ulcerative colitis.


Considerations regarding centromere assembly in plant whole-genome sequencing.
The assembly of centromeric regions has become one of the most intractable tasks in whole-genome sequencing due to the enrichment of highly repetitive DNA sequences in most eukaryotic centromeres. Here, we describe a method used to identify centromeric DNAs through chromatin immunoprecipitation and sequencing (ChIP-seq). By mapping ChIP-seq reads, centromeric regions can be indicated in genome assemblies. We demonstrated that the assembly quality of centromeres obtained using ChIP-seq mapping can reflect and indicate the quality of a whole-genome assembly. We discuss an expected 'high-quality' centromere assembly obtained via centromere ChIP-seq mapping.


Untargeted metabolomic approaches in food authenticity: A review that showcases biomarkers.
The assessment of food authenticity is a topic that gained a lot of interest at the international level. This term includes misidentification of variety, origin, production system, processing but also adulteration. These frauds all have an analytical component, and research tends to offer new analytical solutions to manage them. One of them is non-targeted approaches, which get around the limitations of targeted analysis by detecting the unexpected. A wide range of products are studied such as wine, rice, olive oil, spices, and honey among the top five. Geographic origin is by far the fraud with the most attention. The main reason is probably the complexity to consider terroir effect and every other variable to determine an area of production. This review offers an overview of the potential of non-targeted analysis to assess food authenticity. These results also illustrate the capability to look for environmental terroir markers that could be cross-matrixes.


Domain-dependent effects of DAT inhibition in the rat dorsal striatum.
The rat dorsal striatum exhibits domain-dependent kinetics of dopamine release and clearance. The present report describes the domain-dependent actions of nomifensine (20 mg/kg i.p.), a competitive dopamine uptake inhibitor, on evoked dopamine responses recorded by voltammetry during electrical stimulation of the medial forebrain bundle. In slow domains, nomifensine increases the initial rate of evoked overflow, increases response overshoot, does not affect the slope of the linear segment of the dopamine clearance profile, and slows the non-linear segment of the clearance profile. In fast domains, nomifensine does not affect the initial rate of overflow, increases the end-of-stimulus overshoot, and decreases the slope of the linear segment of the dopamine clearance profile. Collectively, these findings do not concur with existing models of evoked dopamine release that describe the effect of nomifensine as an increase in the effective KM of dopamine uptake. These findings suggest that dopamine clearance after evoked release is affected by both dopamine uptake and a restricted extracellular diffusion process.


Mechanism of hydrogen activation by [NiFe] hydrogenases.
The active site of [NiFe] hydrogenases contains a strictly conserved arginine that suspends a guanidine nitrogen atom <4.5 Å above the nickel and iron atoms. The guanidine headgroup interacts with the side chains of two conserved aspartic acid residues to complete an outer-shell canopy that has thus far proved intractable to investigation by site-directed mutagenesis. Using hydrogenase-1 from Escherichia coli, the strictly conserved residues R509 and D574 have been replaced by lysine (R509K) and asparagine (D574N) and the highly conserved D118 has been replaced by alanine (D118A) or asparagine (D118N/D574N). Each enzyme variant is stable, and their [(RS)2Niμ(SR)2Fe(CO)(CN)2] inner coordination shells are virtually unchanged. The R509K variant had >100-fold lower activity than native enzyme. Conversely, the variants D574N, D118A and D118N/D574N, in which the position of the guanidine headgroup is retained, showed 83%, 26% and 20% activity, respectively. The special kinetic requirement for R509 implicates the suspended guanidine group as the general base in H2 activation by [NiFe] hydrogenases.


The new Japanese Classification of Gastric Carcinoma: Points to be revised.
SUMMARY OF CHANGES:1. The previous version described clinical, surgical and conclusive staging. This version retains clinical and surgical staging, being the staging before and during definitive surgery respectively. Conclusive staging is now defined as final staging, and may include information for which there is no histological proof (e.g. hepatic metastases). Pathological staging has been introduced, and requires microscopic proof.2. Lymph node staging has been extensively revised. A 3 tier system replaces the previous 4 tier system, and thus there are now 4 possible N stages (N0-3). The definition of some node groupings have been more precisely defined (No.11 and No.12).3. Lymph node dissection is classified D0-3 based on the new nodal groups. Minor modifications of the extent of dissection have been made. "Optional" stations have been omitted.4. Peritoneal cytology has been included in the staging system.6. Rules for staging carcinoma of the remnant stomach have been introduced.7. Rules to classify and evaluate endoscopic mucosal resection (EMR) have been introduced.8. Subclassification of T staging has been introduced for T1 (M and SM) and T2 (MP and SS) tumors.9. Nomenclature has been simplified: lower case letters are only used to define the "type" of staging (c clinical; s surgical; p pathological; f final). Tumor location is now defined as U (upper third), M (middle) or L (lower), replacing C, M, A. Proximal and distal margins are designated as PM and DM (previously OW and AW). LM and VM have been introduced for the lateral and vertical margins of EMR specimens.


Do we parse the background into separate streams in the cocktail party?
In the cocktail party situation, people with normal hearing usually follow a single speaker among multiple concurrent ones. However, there is no agreement in the literature as to whether the background is segregated into multiple streams/speakers. The current study varied the number of concurrent speech streams and investigated target detection and memory for the contents of a target stream as well as the processing of distractors. A male-voiced target stream was either presented alone (single-speech), together with one male-voiced distractor (one-distractor), or a male- and a female-voiced distractor (two-distractor). Behavioral measures of target detection and content tracking performance as well as target- and distractor detection related event-related brain potentials (ERPs) were assessed. We found that the N2 amplitude decreased whereas the P3 amplitude increased from the single-speech to the concurrent speech streams conditions. Importantly, the behavioral effect of distractors differed between the conditions with one vs. two distractor speech streams and the non-zero voltages in the N2 time window for distractor numerals and in the P3 time window for syntactic violations appearing in the non-target speech stream significantly differed between the one- and two-distractor conditions for the same (male) speaker. These results support the notion that the two background speech streams are segregated, as they show that distractors and syntactic violations appearing in the non-target streams are processed even when two speech non-target speech streams are delivered together with the target stream.


Hydrodynamic immunization leads to poor CD8 T-cell expansion, low frequency of memory CTLs and ineffective antiviral protection.
Hepatotropic pathogens, such as hepatitis B (HBV) and hepatitis C (HCV), often escape cellular immune clearance resulting in chronic infection. As HBV and HCV infections are the most common causes of hepatocellular carcinoma (HCC), prevention of these infections is believed to be key to the prevention of HCC. It is believed that an effective immune therapy must induce strong cytotonic T lymphocytes (CTLs) that can migrate into the liver, where they can clear infected hepatocytes. Here, we compared the induction of CD8 T cells by two different DNA immunization methods for T-cell differentiation, function, memory programming and their distribution within relevant tissues in a highly controlled fashion. We used hydrodynamic tail vein injection of plasmid to establish liver-specific LCMV-gp antigen (Ag) transient expression, and studied CD8 T cells induced using the P14 transgenic mouse model. CD8 T cells from this group exhibited unique and limited expansion, memory differentiation, polyfunctionality and cytotoxicity compared with T cells generated in intramuscularly immunized mice. This difference in liver-generated expansion resulted in lower memory CD8 T-cell frequency, leading to reduced protection against lethal viral challenge. These data show an unusual induction of naive CD8 T cells contributed to the lower frequency of Ag-specific CTLs observed after immunization in the liver, suggesting that limited priming in liver compared with peripheral tissues is responsible for this outcome.


Correction: (TIMP2) x (IGFBP7) as early renal biomarker for the prediction of acute kidney injury in aortic surgery (TIGER). A single center observational study.
[This corrects the article DOI: 10.1371/journal.pone.0244658.].


Flavones interact with fiber to affect fecal bacterial communities in vitro.
This study investigated the effects of the sugarcane flavones diosmin, diosmetin, luteolin, and tricin, and their interactions with sugarcane fiber on the modulation of gut microbiota using in vitro batch fermentation. The alteration of fecal fermentation bacterial profile was analyzed using 16S rRNA sequencing data, while the bioavailability of fiber was indicated by short-chain fatty acid (SCFA) production and metabolism of polyphenols was measured directly by phenolic metabolites. Application of diosmin, diosmetin, luteolin, and tricin without fiber had no significant effect on the overall microbiota profile after 24 h of fermentation. When fiber alone was added, total SCFA production increased, specifically that of propionic and valeric acids. However, when flavones were combined with fiber, synergistic effects on the modulation of relative abundances of different bacterial taxa was noted. In particular, the proportion of Prevotella spp. was significantly increased by the combinations of diosmin, luteolin, and tricin with fiber.


Hemoglobin-oxygen affinity in anemia.
In blood of 21 anemic patients and 8 normal subjects (N) three oxygen dissociation curves each were measured at different pH values to calculate Bohr coefficients after acidification with CO2 (BCCO2) or fixed acid (BCFA), and other important parameters of oxygen affinity. The patients had either low hemoglobin or red cell production (L: n = 11, 7.3 g/dl Hb) or high erythrocyte production combined with high loss (H: n = 10, 7.8 g/dl Hb). The standard half saturation pressure P50 (pH 7.4, 37 degrees C) was equally elevated in both anemic groups (L: 30.5, H: 30.8, N: 26.7 mmHg), as well as the diphosphoglycerate concentration (DPG) (L: 18.7, H: 18.6, N: 12.7 mumol/g Hb). The red cell pH of the anemics was lower than for the N (approximately 0.045 units) causing part of the difference in P50. Hill's "n" tended to high values in the anemics except at low O2-saturation in the H. For BCCO2 no significant difference among the groups was observed. BCFA, however, increased in the H at low SO2 compared to the N and L. The cause for most of the changes in hemoglobin oxygen affinity in anemics was the high [DPG]. The combination of high P50 and high "n" value as in the L seems to be most advantageous for tissue oxygenation.


Cardiovascular effects of various colloidal solutions during major abdominal surgery.
We examined the effects of various colloidal solutions on cardiovascular and oxygen transport variables for 26 patients undergoing gastrectomy under general anesthesia. Fluosol-DA, whole blood, 3% Dextran-40 (Saviosol), and 6% hydroxyethyl starch (hetastarch, Hespan) affected the right side of heart, but only whole blood and Fluosol-DA significantly increased cardiac output and oxygen delivery (DO2). Fluosol-DA may prove useful for critical care of hemorrhagic shock during operation or resuscitation in the immediate postoperative period.


Percutaneous retrograde screwing for stabilisation of acetabular fractures.
To evaluate the results of retrograde percutaneous screw fixation (PSF) in minimally or undisplaced acetabular fractures in a geriatric population. Between July 1998 and July 2001, 21 consecutive patients with an acetabular fracture underwent fluoroscopic guided percutaneous fixation. The mean age was 81 years (range 67--90 years). In all cases, the fracture was minimally or undisplaced (<2mm). Two cannulated cancellous 7.3mm screws were inserted in a retrograde fashion to stabilise the posterior and the anterior column. Bed to chair transfer began after 24h. Weight bearing as tolerated was allowed at 4 weeks. Eighteen patients were reviewed at a mean of 3.5 years (range 2--5 years). Soft tissue dissection was minimal. There were no intraoperative or postoperative complications. At the latest follow-up there was no radiographical evidence of secondary displacement of fragments, degenerative changes, or screw failure. Fractures healed at a mean time of 12 weeks (range 8--15 weeks). Clinical results were satisfactory in 17 patients. Our results show that percutaneous screw fixation under fluoroscopic control is a safe technique to treat some pattern of acetabular fracture.


Words of wisdom. Re: Phase 1 trial of high-dose exogenous testosterone in patients with castration-resistant metastatic prostate cancer. Morris MJ, Huang D, Kelly WK, et al. Eur Urol 2009;56:237-44.
Laboratory studies suggest that castration-resistant prostate cancer (CRPC) cell growth is suppressed by supraphysiologic doses of testosterone (T). In this study, 12 men received high doses of T transdermally for 7 d, for 4 mo, or until progression.The approach was safe and toxicity was mild, but responses were modest. Because serum T did not reach intended supraphysiologic levels, the authors urged more clinical testing.


New bone formation in nongrafted sinus lifting with space-maintaining management: a novel technique using a titanium bone fixation device.
Sinus lifting without graft materials allows new bone formation in the sinus, but the amount of bone formation varies. This study aimed to investigate whether nongrafted sinus lifting using a titanium bone fixation device can promote bone formation in the sinus. Patients with atrophic posterior maxillae jeopardizing implant stability were included. After nongrafted sinus lifting in combination with implant placement, repositioning of the bone window and additional space-maintaining management were performed by use of the bone fixation device. The primary variables recorded retrospectively included implant survival and preoperative and postoperative alveolar crest height with and without Schneiderian membrane perforation. Independent variables included patient demographics, position and dimension of the implants, complications, and follow-up period. The t test was used for comparing differences in bone levels. The implant survival rate was estimated by uses of Kaplan-Meier statistics. The study included 11 patients (4 men and 7 women) and a total of 21 implants. Radiographically, new bone formation around the implant was generally observed in accordance with the implant apex. Postoperative alveolar crest height (mean, 10.9 ± 2.2 mm) was significantly higher compared with residual alveolar crest height (mean, 4.7 ± 1.4 mm), and no significant difference in bone formation was seen according to membrane perforation. The cumulative survival rate was 95.2%. This nongrafted sinus-lifting procedure using a bone fixation device could attain predictable bone formation. Additional space-maintaining management using a bone fixation device in a nongrafted sinus lift offers a useful technique for promoting bone formation in the sinus.


GLP-1 signaling preserves cardiac function in endotoxemic Fischer 344 and DPP4-deficient rats.
Glucagon-like peptide-1 (GLP-1) is rapidly cleaved by widely expressed dipeptidyl peptidase-4 (DPP4) enzyme. Both DPP4 inhibitors and GLP-1 analogue are being developed as a novel class of oral antihyperglycemic agent in the treatment of diabetes. However, the benefits of both agents on the cardiovascular function of endotoxemic animals remains poorly understood. In this study, the cardiac function of wild-type and DPP4-deficient rats was evaluated by pressure-volume loops in control and 4 h after lipopolysaccharide (LPS, 10 mg/kg, i.v.) treatment. LPS-induced suppression of cardiovascular function in wild-type rats was associated with a significant reduction in cardiac cAMP level, phosphorylation of phospholamban, and attenuation of aortic contractile response to phenylephrine. DPP4-deficient rats had better preservation of cardiovascular function than wild-type rats during endotoxemia, which was correlated with a more prominent elevation of GLP-1 signaling. These findings coincided with the pretreatment of GLP-1 analogue, exendin-4, where the deterioration of cardiovascular function during endotoxemia was significantly reversed in wild-type rats. Furthermore, the benefit of DPP4 deficiency or GLP-1 analogue not only preserved cardiovascular function but also alleviated multiple organ injury and improved survival rate during endotoxemia. In summary, this study demonstrated that the resistance to LPS in DPP4-deficient rats seems to be derived from the higher GLP-1 production, and exendin-4 prevents cardiac dysfunction in wild-type rats with endotoxemia. This study proves that GLP-1 agonists or DPP4 inhibitor may possibly be used as a preventive or even as a novel therapeutic agent in septic shock.


Randomized trial of diet versus diet plus cardiovascular conditioning on glucose levels in gestational diabetes.
We studied the impact of a training program on glucose tolerance in gestational diabetes mellitus. Women with gestational diabetes mellitus (N = 19) were randomized into either group I, a 6-week diet alone group (24 to 30 kcal/kg/24 hours; 20% protein, 40% carbohydrate, 40% fat), or group II, which followed the same diet plus exercise (20 minutes three times a week for 6 weeks). An arm ergometer was used to maintain heart rate in the training range. Glycemic response was monitored by glycosylated hemoglobin, a 50 gm oral glucose challenge with a fasting and 1-hour plasma glucose, and blood glucose self-monitoring, fasting and 1 hour after meals. Week 1 glycemic parameters were the same for both groups. Week 6 data (mean +/- SD) were as follows: group I glycosylated hemoglobin, 4.7% + 0.2% versus group II, 4.2% +/- 0.2%; p less than 0.001. The group I glucose challenge fasting value was 87.6 +/- 6.2 versus 70.1 +/- 6.6 mg/dl, p less than 0.001 for group II. The group I 1-hour plasma glucose challenge result was 187.5 +/- 12.9 mg/dl versus 105.9 +/- 18.9 mg/dl for group II, p less than 0.001. The glycemic levels diverged between the groups at week 4. We conclude that arm ergometer training is feasible in women with gestational diabetes mellitus and results in lower glycosylated hemoglobin, fasting, and 1-hour plasma glucose concentrations than diet alone. Arm ergometer training may provide a useful treatment option for women with gestational diabetes mellitus and may obviate insulin treatment.


ATM-dependent activation of the gene encoding MAP kinase phosphatase 5 by radiomimetic DNA damage.
Cellular responses to DNA damage are mediated by an extensive network of signaling pathways. The ATM protein kinase is a master regulator of the response to double-strand breaks (DSBs), the most cytotoxic DNA lesion caused by ionizing radiation. ATM is the protein missing or inactive in patients with the pleiotropic genetic disorder ataxia-telangiectasia (A-T). A major response to DNA damage is altered expression of numerous genes. While studying gene expression in control and A-T cells following treatment with the radiomimetic chemical neocarzinostatin (NCS), we identified an expressed sequence tag that represented a gene that was induced by DSBs in an ATM-dependent manner. The corresponding cDNA encoded a dual specificity phosphatase of the MAP kinase phosphatase family, MKP-5. MKP-5 dephosphorylates and inactivates the stress-activated MAP kinases JNK and p38. The phosphorylation-dephosphorylation cycle of JNK and p38 by NCS was attenuated in A-T cells. Thus, ATM modulates this cycle in response to DSBs. These results further highlight ATM as a link between the DNA damage response and major signaling pathways involved in proliferative and apoptotic processes.