First reported case of Gilbertella persicaria in human stool: outcome of a community study from Segamat, Johor, Malaysia.
Species of fungi belonging to the order Mucorales can be found everywhere in the environment. Gilbertella persicaria, which belongs to this order, have often been isolated from fruits and in water systems. However, there has been no report of isolation of this fungus from human samples. During a gut mycobiome study, from the Segamat community, Gilbertella persicaria was isolated from a human fecal sample and was characterized through a series of morphological assessment, biochemical tests, and molecular techniques. The isolate produced a white velvety surface that turned grayish after 24 h. Although no biofilm production was observed, the results indicated that the isolate could form calcium oxalate crystals, produced urease, and was resistant to low pH. The isolate was sensitive to amphotericin but resistant to voriconazole and itraconazole. The features of this fungus that could help in its survival in the human gut are also discussed.


Fluticasone furoate/vilanterol (100/25; 200/25 μg) improves lung function in COPD: a randomised trial.
Once-daily combination treatment is an attractive maintenance therapy for COPD. However, the dose of inhaled corticosteroid to use in a once-daily combination is unknown. We compared two strengths of fluticasone furoate (FF) plus vilanterol (VI), the same strengths of the individual components, and placebo. Multicentre, randomised, 24-week, double-blind, placebo-controlled, parallel-group study in stable, moderate-to-severe COPD subjects (N = 1224). Subjects were randomised to FF/VI (200/25 μg; 100/25 μg), FF (200 μg; 100 μg), VI 25 μg, or placebo, once daily in the morning. Co-primary efficacy endpoints; 0-4 h weighted mean (wm) FEV(1) on day 168, and change from baseline in trough (23-24 h post-dose) FEV(1) on day 169. The primary safety objective was adverse events (AEs). There was a statistically significant (p < 0.001) increase in wm FEV(1) (209 ml) and trough FEV(1) (131 ml) for FF/VI 200/25 μg vs. placebo; similar changes were seen for FF/VI 100/25 μg vs. placebo. Whereas the difference between FF/VI 200/25 μg and VI 25 μg in change from baseline trough FEV(1) (32 ml) was not statistically significant (p = 0.224), the difference between FF/VI 200/25 μg and FF 200 μg for wm FEV(1) (168 ml) was significantly different (p < 0.001). VI 25 μg significantly improved wm and trough FEV(1) vs. placebo (185 ml and 100 ml, [corrected] respectively). No increase was seen in on-treatment AEs or serious AEs (SAEs), with active therapy vs. placebo. FF/VI provides rapid and significant sustained improvement in FEV(1) in subjects with moderate-to-severe COPD, which was not influenced by the dose of FF. These data suggest that FF/VI may offer clinical efficacy in COPD and warrants additional study. GSK study number: HZC112207. ClinicalTrials.gov: NCT01054885.


[interest of scaphal cartilage grafting or ulnar proximal bone graft, under the olecranium, in secondary nose repair].
The proper use of scaphal ear cartilaginous autograft or ulnar bone lateral side under the olecranium, on the postero-médial flat wall covered by muscle, may be an innovative way for secondary nasal repair or reconstruction.These techniques are not well popularised, but they may represent a good solution in complicated cases when straighter cartilage than the concha, or a planar bone graft easy to take out, are considered; this may be the case mostly in secondary noses surgery;These techniques are also easy to perform because the position to take the grafts is very easy, the donor site is under the operative field; the observed complications have been few and the results were rewarding.


Characterization of bhatooru, a traditional fermented food of Himachal Pradesh: microbiological and biochemical aspects.
A number of traditional fermented products are prepared and consumed in Himachal and the types of traditional fermented products of Himachal are unique and different from other areas. Bhatooru is an indigenous leavened bread or roti and constitutes the staple diet of rural population of Himachal. The microbiological analysis of the inoculums (malera) revealed that it composed of a consortium of microorganisms. Population of Lactobacillus, Leuconostoc and Saccharomyces cerevisiae increased from 4.77 to 8.0 log cfu/g of dry matter in 10 h of fermentation. The amount of total proteins increased from 13.6 to 18.4 % (w/w). The total sugars during fermentation decreased from 74.1 to 50.1 % (w/w) on dry weight basis. However, the reducing sugar level of the fermenting samples increased significantly from 7.8 to 16.5 mg/g dry matter in the first 4 h and thereafter, it gradually decreased to 10.0 mg/g dry matter. Similarly starch content decreased from 70.2 to 48.3 % (w/w) on dry weight basis by 10 h of fermentation. In fermented samples protease activity increased from 0.48 U/g dry matter to 11.5 U/g in 6 h and then decreased to 3.21 U/g on dry weight basis at 10 h. Amylase activity initially increased from 65.0 to 79.4 U to 6 h and then declined to 69.9 U/g of dry matter. Fermentation in bhatooru significantly enhanced the B vitamin levels especially thiamine, riboflavin and nicotinic acid and essential amino acids viz methionine, phenylalanine, threonine, lysine and leucine.


Selective Pseudocapacitive Deionization of Calcium Ions in Copper Hexacyanoferrate.
In recent years, the capacitive deionization (CDI) technology has gradually become a promising technology for hard water treatment. Up to now, most of the work for water softening in CDI was severely limited by the inferior selectivity and electrosorption performances of carbon-based electrodes in spite of combining Ca2+-selective ion-exchange resin or membranes. Pseudocapacitive electrode materials that selectively interact with specific ions by Faradic redox reactions or ion (de)intercalation offer an alternative strategy for highly selective electrosorption of Ca2+ from water because of brilliant ion adsorption capacity. Here, we first used copper hexacyanoferrate (CuHCF) as a pseudocapacitive electrode to methodically study the selective pseudocapacitive deionization of Ca2+ over Na+ and Mg2+. Using the hybrid CDI cell consisting of a CuHCF cathode and an activated carbon anode without any ion-exchange membrane, the outstanding Ca2+ electrosorption capacity of 42.8 mg·g-1 and superior selectivity &(Ca2+/Na+) of 3.05 at a molar ratio of 10:1 were obtained at 1.4 V, surpassing those of the reported carbon-based electrodes. Finally, electrochemical measurements and molecular dynamics (MD) simulations provided an in-depth understanding of the selective pseudocapacitive deionization of Ca2+ ions in a CuHCF electrode. Our study would be helpful for developing high-efficiency selective electrosorption of target charged ions by intrinsic properties of pseudocapacitive materials.


Cultural characteristics and zearalenone production by strains ofFusarium from wheat.
Conidia of the speciesFusarium culmorum /W.G.Sm./ Sacc. andFusarium graminearum Schwabe are characterized by variability in zearalenone production and dimensions depending on the substrate. The sporulation of isolates from some wheat eultivars have been deprived in vivo and in vitro in the first passage, but not their pathogenicity and toxic metabolites production. Nonsporulating strains produced lower quantités of zearalenone than sporulating ones. Liquid filtrates of such nonsporulating strains had a high phytotoxic effect on wheat caryopses. The crystalline toxin DAS /0,25 ug/ml/ had low phytotoxic effect on wheat caryopses.


Cross-sectional and longitudinal evaluation of uterine artery Doppler velocimetry for the prediction of pre-eclampsia in normotensive women with specific risk factors.
To evaluate the performance, in the prediction of pre-eclampsia, of (1) an abnormal mean uterine artery resistance index (RI; cross-sectional index) at 24 weeks of gestation, (2) the individual longitudinal flow pattern of results observed at 16, 20 and 24 weeks of gestation and (3) a multiple logistic regression model including the individual longitudinal flow pattern and the mean RI at 24 weeks. A total of 144 normotensive pregnant women with risk factors for pre-eclampsia were evaluated with uterine artery color Doppler at 16, 20 and 24 weeks' gestation. The following indices were obtained: (1) cross-sectional index: the mean RI of both uterine arteries at 24 weeks' gestation was calculated for each patient and considered abnormal when >/= 0.58; (2) longitudinal indices: the individual longitudinal flow pattern of mean RI of both the main uterine arteries at 16, 20 and 24 weeks' gestation was derived for each subject and defined as (a) the typical physiological flow pattern, with a trend of decrease in values or (b) the non-physiological flow pattern. The probability of having a pregnancy complicated by pre-eclampsia was also calculated by means of a multivariate logit model. The log-odds was modeled as a function of variables related to maternal characteristics, the individual longitudinal flow pattern indicator, and of the mean RI at 24 weeks' gestation as a continuous variable. Pregnancies had a physiological course in 108 (75%) women, while 36 (25%) women developed pre-eclampsia during the third trimester. For the prediction of pre-eclampsia, the use of an abnormal uterine artery RI index (> or = 0.58) at 24 weeks showed a sensitivity of 77.8%, a specificity of 67.6%, a positive predictive value (PPV) of 44.4% and a negative predictive value (NPV) of 90.1%, with a likelihood ratio (LR) for an abnormal test of 2.4; with the longitudinal flow pattern indicator, sensitivity was 88.9%, specificity 82.4%, PPV 62.7% and NPV 95.7%, with a LR for an abnormal test of 4.9; the use of a logit model yielded a sensitivity of 72.2%, a specificity of 90.7%, a PPV of 72.2% and a NPV of 90.7%, with a LR for an abnormal test of 8.0. In this study the use of an individual longitudinal flow pattern indicator resulted in improving accuracy in the prediction of pre-eclampsia as compared with the traditional cross-sectional mean RI at 24 weeks. A further increase in specificity and PPV was obtained using a logit model that includes the longitudinal flow pattern indicator and the cross-sectional RI at 24 weeks. Since both the longitudinal flow pattern indicator and the logit model showed a high performance in predicting pre-eclampsia in women with risk factors for impaired placentation, they might be used to identify a high-risk population in which preventive measures and/or therapeutic options might be tested.


Occupational asthma caused by isonicotinic acid hydrazide (INH) inhalation.
Occupational asthma caused by isonicotinic acid hydrazide (INH) inhalation occurred in a 26-year-old female hospital pharmacist after symptoms of allergic rhinitis. Intradermal, inhalation, and Prausnitz-Küstner tests were performed with INH dissolved in saline, INH dissolved in the subject's serum and incubated at 25 degrees C for 4 hours, and an INH conjugate with human serum albumin. An INH conjugate with bovine serum albumin was also used in the prick tests alone. All preparations caused rapid positive skin reaction in the patient. Prausnitz-Küstner tests on the subject's mother were also rapidly positive. Furthermore, positive results were obtained not only in the inhalation tests with the three antigens but also in the environmental provocation tests. These results strongly suggested that the asthmatic symptoms of the subject were not caused by physical irritation from INH or other drugs and might be mediated by an IgE antibody specific to INH, a suggestion subsequently confirmed by in vitro enzyme-linked allergosorbent test for the antibody previously reported. This is the first precise description of INH-induced bronchial asthma, and the four kinds of INH preparations used in these tests might be very useful as tools of clinical diagnosis in INH allergy.


No difference in COVID-19 treatment outcomes among current methamphetamine, cannabis and alcohol users.
Poor outcomes of COVID-19 have been reported in older males with medical comorbidities including substance use disorder. However, it is unknown whether there is a difference in COVID-19 treatment outcomes between patients who are current cannabis users, excessive alcohol drinkers and those who use a known hazardous stimulant such as methamphetamine (METH). Electronic medical records (EMR) of COVID-19 patients with current METH (n = 32), cannabis (n = 46), and heavy alcohol use (n = 44) were reviewed. COVID-19 infection was confirmed by positive SARS-CoV-2 PCR test, current drug use was confirmed by positive urine drug testing, and alcohol use was identified by a blood alcohol concentration greater than 11 mg/dl. Multivariate linear regression models as well as the firth logistic regression models were used to examine the effect of substance use group (METH, cannabis, or alcohol) on treatment outcome measures. A total of 122 patients were included in this analysis. There were no significant differences found between drug groups in regards to key SARS-CoV-2 outcomes of interest including ICU admission, length of stay, interval between SARS-CoV-2 positive test and hospital discharge, delirium, intubation and mortality after adjusting for covariates. About one-fifth (21.9% in METH users, 15.2% in cannabis users, and 20.5% in alcohol users) of all patients required ICU admission. As many as 37.5% of METH users, 23.9% of cannabis users, and 29.5% of alcohol users developed delirium (P = 0.4). There were no significant differences between drug groups in COVID-19 specific medication requirements. Eight patients in total died within 10 months of positive SARS-CoV-2 PCR test. Two patients from the METH group (6.3%), two patients from the cannabis group (4.3%), and four patients from the alcohol group (9.1%) died. The study outcomes may have been affected by several limitations. These included the methodology of its retrospective design, relatively small sample size, and the absence of a COVID-19 negative control group. In addition, there was no quantification of substance use and many covariates relied on clinical documentation or patient self-report. Finally, it was difficult to control for all potential confounders particularly given the small sample size. Despite these limitations, our results show that current METH, cannabis, and heavy alcohol users in this study have similar treatment outcomes and suffer from high morbidity including in-hospital delirium and high mortality rates within the first-year post COVID-19. The extent to which co-morbid tobacco smoking contributed to the negative outcomes in METH, cannabis, and alcohol users remains to be investigated.


Narrative thought and decision-making.
A significant body of literature has identified how narrative provides a basis for perceiving and understanding human experience. In the target article, the authors arrive at the need for a form of narrative-based reasoning due to constraints that render probabilistic-based reasoning ineffective. This commentary attempts to bridge this gap and identify links between the proposed and existing theories.


Evolutionary biology: genomic clues to original sex in fungi.
Sexual identity in fungi is conferred by a diverse group of transcription factors. Analysis of a Zygomycota genome, representing a basal branch within the fungi, indicates that HMG-domain proteins were present as ancestral sex determinants and suggests a mechanism for the evolution of eukaryotic sex chromosomes.


Basic and applied research at the TRIUMF meson factory.
The TRIUMF 520 MeV H- cyclotron produces intense beams of protons, pions and muons supporting basic research in nuclear, particle and solid-state physics, nuclear chemistry and biomedicine, and applied research in electromagnetic breeding of nuclear fuel, proton radiography, radioisotope production and cancer treatment.


Combined Racial and Gender Differences in the Long-Term Predictive Role of Education on Depressive Symptoms and Chronic Medical Conditions.
Despite a well-established literature on the protective effect of education on health, less is known about group differences in the mechanisms underlying this association. Using a life course approach and cumulative advantage theory, this study compared Black men, Black women, White men, and White women to assess the long-term gradient (education as a continuous measure) and threshold (>12 years) effects of baseline education on change in chronic medical conditions (CMC) and depressive symptoms (DS) from baseline to 25 years later. Data came from the Americans' Changing Lives Study, 1986-2011. The study followed Black and White respondents for up to 25 years, among whom 1271 individuals who had survived and were under follow-up were interviewed in 2011 and reported their number of chronic medical conditions and depressive symptoms (Center for Epidemiological Studies-Depression; CES-D 11). Multi-group structural equation modeling was used to compare gradient and threshold effects of education on change in chronic medical conditions and depressive symptoms from baseline (1986) to 25 years later (2011) among Black men, Black women, White men, and White women. There were group differences in the long-term association between education measured as a gradient and the change in depressive symptoms and chronic medical conditions during the follow-up, and in the association between education measured at the threshold of 12 years on change in depressive symptoms from baseline to follow-up. However, the association between education measured at this threshold and change in chronic medical conditions did not differ across race-gender groups. With the exception of Black men, who showed a gradient protective effect for baseline education against increase in the number of chronic medical associations (threshold or gradient) with change in chronic medical conditions. Among White men and White women, education had a threshold protective effect against increase in depressive symptoms from baseline to 25 years later. Black men and women showed a gradient protective effect of baseline education against an increase in depressive symptoms over the 25-year follow-up period, but unexpectedly, a threshold effect of education was also found to be associated with an increase in depressive symptoms over the follow-up period among Black men. This finding suggests that although Black men benefit from each incremental increase in education, those who graduated from high school were at an additional risk of depressive symptoms over a 25-year period. Findings suggest that the intersection of race and gender influences how education is associated with long-term changes in physical and mental health of individuals from baseline to 25 years later. As the shape of the association between education and health depends on the intersection of race and gender, these groups may vary for operant mechanisms by which education operates as a main social determinant of health.


Analysis of the effect of electrostatic energy truncation in molecular dynamics simulations of immunoglobulin G light chain dimer.
Molecular dynamics (MD) simulations of immunoglobulin G (IgG) light chain dimer using particle mesh Ewald (PME) and cutoff methods of treating electrostatic interactions were performed. The results indicate that structural parameters (RMSD, radius of gyration, solvent accessible surface) are very similar for both schemes; however, PME simulation shows increased mobility of side chains. This leads to larger fluctuations in the distance between the monomers in the dimer molecule, and, as a consequence, results in decreased number of interactions across the dimer interface. The wall clock time of the simulations was also compared. It was shown that the PME method is approximately 30% faster than the cutoff method for the system studied on a single processor.


Influence of high pressure homogenization and pasteurization on the in vitro bioaccessibility of carotenoids and flavonoids in orange juice.
Production of high-quality healthy foods through sustainable methodologies is an urgent necessity. High pressure homogenization (HPH) is an interesting alternative to obtain premium citrus juices, but its effects on bioactive compounds are unclear. There was studied the influence of HPH (150 MPa) and pasteurization (92 °C for 30 s and 85 °C for 15 s) processing on physicochemical properties and in vitro bioaccessibility of carotenoids and flavonoids in orange juices. Regarding fresh juice, physicochemical properties of samples remained unchanged although cloudiness was improved by homogenization. Pasteurization did not affect total carotenoids content and retinol activity equivalents (RAE) of juices whereas homogenization yielded a significant reduction (1.37 and 1.35-fold, respectively). Interestingly, particle size reduction from homogenization drastically enhanced (about 5-fold) bioaccessibility of carotenoids including hardly bioaccessible epoxycarotenoids, finding unaltered rates in pasteurized samples. Bioaccessibility of flavonoids was constant in all cases. Results can promote HPH as an efficient option to obtain health-enhanced foods.


Thin films exhibiting multicolor changes induced by formaldehyde-responsive release of anionic dyes.
A novel methodology for the sensing of formaldehyde that displays a response using distinct and diverse color changes is reported. Through copolymerization of a primary amine monomer with additional co-monomers on a pattern-printed microscope slide, primary amine-containing thin films were obtained. After the absorption of a range of colors of anionic dyes, the thin films were immersed in aqueous formaldehyde solutions. It was demonstrated that the color of the thin films changed depending on the formaldehyde concentration in the solution. As the anionic dyes were released from the thin films at varying formaldehyde concentrations, a set of thin films exhibiting a range of color-change patterns was observed. The response selectivity of the thin films towards carbonyl compounds was examined, and sensitivity in the order of formaldehyde»acetaldehyde>acetone was observed. In addition, the effect of amine structure was examined, and it was found that thin films bearing tertiary amino groups show virtually no formaldehyde response. These observations clearly indicate that the existence of primary amino groups is essential for color changes to be observed, and that the formation of an imine is the crucial step in generating a response against formaldehyde. The formaldehyde-responsive system presented herein is advantageous, as its preparation is relatively simple and does not require complex organic synthesis. In addition, a wide range of anionic dyes is compatible with the system, and can be selected in terms of color, charge, toxicology profile, and cost, for example.


Perioperative stroke in parapharyngeal space schwannoma: an unusual, dreaded complication.
Post-styloid parapharyngeal space tumours (PPS) have a notorious course owing to their anatomy and proximity to neurovascular bundles. Nerve injuries are usual outcomes in schwannomas. Our case is the first documented complication of contralateral hemiplegia occurring in the postoperative period in a benign PPS tumour. A 24-year-old presented with a swelling on the left lateral aspect of the neck, diagnosed as a PPS schwannoma. He underwent transcervical excision with mandibulotomy with extracapsular dissection of the tumour. Contralateral hemiplegia, as a dreaded complication, was encountered. He was managed conservatively according to ASPECTS stroke guidelines by the critical care team. On a regular follow-up, he noticed an improvement in the lower limb with subsequent upper limb power. Perioperative stroke is a dreaded complication involving PPS in large benign tumours. To prevent unforeseen circumstances, necessary preoperative patient counselling and immense intraoperative care should be taken while dissecting the major vessels.


Mental health care preferences among low-income and minority women.
Mental health care preferences are examined among 1,893 low-income immigrant and U.S.-born women with an acknowledged emotional problem (mean age = 29.1, SD = 89.6). Ethnicity, depression, somatization, and stigma are examined as they relate to mental health care preferences (medication, individual and group counseling, faith, family/friends). Seventy-eight percent of participants counseling would be helpful; 55%; group counseling; and 32% medication. Faith was cited by 81%; family and friends were endorsed by 65%. Minorities had lower odds than Whites of endorsing medication (Black immigrants: OR = 0.27, p < 0.001, U.S.-born Blacks: OR = 0.30, p < 0.001, immigrant Latinas: OR = 0.50, p < 0.01). Most minorities also had higher odds of endorsing faith compared to Whites (Black immigrants: OR = 3.62, p < 0.001; U.S.-born Blacks, OR = 3.85, p < 0.001; immigrant Latinas: OR = 9.76, p < 0.001). Being depressed was positively associated with endorsing medication (OR = 1.93, p < 0.001), individual counseling (OR = 2.66, p < 0.001), and group counseling (OR = 1.35, p < 0.01). Somatization was positively associated with endorsing medication (OR = 1.29, p < 0.05) and faith (OR = 1.37, p < 0.05). Stigma-concerns reduced the odds of endorsing group counseling (OR = 0.58, p < 0.001). Finally, being in mental health treatment was related to increased odds of endorsing medication (OR = 3.88, p < 0.001) and individual counseling (OR = 2.29, p = 0.001).


Is age-related macular degeneration associated with pinguecula or scleral plaque formation?
To evaluate whether ocular changes indicating an increased exposure to UV irradiation are associated with the development of age-related macular degeneration (ARMD). Using histology, we have investigated a possible association of ocular changes that might be attributed to actinic damage, namely pinguecula and scleral plaque, with findings of both atrophic and disciform ARMD. A total of 74 eyes, could be used for evaluation. Features of ARMD were present in 36 eyes (11 with disciform degeneration and 25 with an atrophic form). A pinguecula was identified in 36 eyes (small in 22 eyes, large in 14 eyes), and a scleral plaque was seen in 5 eyes. While scleral plaque showed an association with ARMD, there was no significant association between pinguecula and ARMD. Our results support the concept of solar radiation having an effect on the development of ARMD but also indicate that it is a multifactorial disease.


Desorbing of decabromodiphenyl ether in low permeability soil and the remediation potential of enhanced electrokinetic.
In this study, desorption kinetic was determined for decabromodiphenyl ether (BDE209) in a low permeability soil, and the remediation potential of hydroxypropyl-β-cyclodextrin (HPCD) enhanced electrokinetic (EK) technique was investigated. The results indicated that the release rate of BDE209 in slowly and very slowly desorbing process was accounted for 31% and 68% in the whole desorption process, respectively. The final desorption rate of BDE209 was 20.7% after 70 h treatment with 5% HPCD in an ideal solution reaction system (without electric field). However, the removal efficiency of BDE209 in section S5 (near anode) of EK1 and EK2 had reached 22% and 20% after 14 days treatment, respectively. Thus it can be assumed that the interaction between BDE209 (on soil particles) and HPCD had been promoted under the electric field. A higher cumulative EOF did not remove more BDE209 with HPCD as facilitating agent, which might due to the low viscosity of HPCD and it did not react completely with BDE209 in soils. In addition, the removal efficiency of BDE209 in section S5 of CK1 and CK2 (without HPCD) had reached 6% and 10%, respectively, which might attribute to the desorption promoting effect of the uniform electric field on hydrophobic organic contaminants. In summary, it is feasible to use the EK to remove BDE209 in low permeability soils using HPCD as solubilizing agent, and the technique key is maintaining sufficient EOF and ensuring the contact reaction efficiency between HPCD and BDE209 synchronously.


Intuitionistic based segmentation of thyroid nodules in ultrasound images.
Accurate delineation of thyroid nodules in ultrasound images is vital for computer-aided diagnosis. Most segmentation methods are semi-automated for thyroid nodules and require manual intervention, which increases the processing time and errors. We propose an automated intuitionistic fuzzy active contour method (IFACM) that integrates intuitionistic fuzzy clustering with an active contour for thyroid nodule segmentation using ultrasound images. Intuitionistic fuzzy clustering is used for the initialization of an active contour and estimation of the parameters required to automatically control the curve evolution. The IFACM was tested extensively on both artificial and real ultrasound images. The IFACM obtained a higher value of true positive (95.1% ± 2.86%), overlap metric (93.1 ± 2.95%), and dice coefficient (90.90 ± 3.08), indicating that the boundary delineated by the IFACM fits best to true nodules. Moreover, it obtained a lower value of false positive (04.1% ± 3.24%) and Hausdorff distance (0.50 ± 0.21 in pixels), further verifying the higher similarity of shape and boundary, respectively. According to the significance test, the results of the proposed method were more significant than those of the other segmentation methods. The main benefit of the IFACM is the automatic identification of nodules on the basis of image characteristics, which eliminates manual intervention. In all the experiments, all initial contours were automatically defined closer to the boundaries of the nodule, which is a benefit of the IFACM. Moreover, this method can segment multiple nodules in a single image efficiently.


Non-classical membrane trafficking processes galore.
Dogmatic views of how proteins and other cellular components may traffic within and between eukaryotic cells have been challenged in the past few years. Beyond the classical secretory/exocytic pathway and its established players, other pathways of cell surface membrane transport, generally termed "unconventional secretion," are now better understood. More insights have also been gleaned on the roles of secreted or shedding microvesicles, either exosomal or ectosomal in origin, in unconventional secretion. Recent works have also revealed key molecular components, particularly the Golgi reassembly stacking protein (GRASP), and the importance of stress-induced autophagy, in unconventional exocytic transport. This GRASP and autophagy-dependent (GAD) mode appears to underlie the unconventional exocytosis of many soluble and membrane cargoes. Likewise, recent findings have revealed transport processes that contrast the classically known mitochondria import, namely vesicular transport from the mitochondria to peroxisomes and lysosomes. Mitochondria-peroxisomal targeting of mitochondria-derived vesicles appears to involve the retromer complex, which was classically associated with endosome-Golgi membrane traffic. The routes of intracellular membrane transport and communications between eukaryotic organelles now appear far more complex that one would have imagined 10 years ago.


Histotripsy: minimally invasive technology for prostatic tissue ablation in an in vivo canine model.
Symptoms of benign prostatic hyperplasia affect men increasingly as they age. Minimally invasive therapies for the treatment of benign prostatic hyperplasia continue to evolve. We describe histotripsy, a noninvasive, nonthermal, focused ultrasound technology for precise tissue ablation, and report the initial results of using histotripsy for prostatic tissue ablation in an in vivo canine model. An annular 18-element, 750-kHz, phased-array ultrasound system delivered high-intensity (22 kW/cm(2)), ultrasound pulses (15 cycles in 20 ms) at pulse repetition frequencies of 100 to 500 Hz to canine prostates. Eight lateral lobe and nine periurethral treatments were performed in 11 anesthetized dogs. Diagnostic ultrasound transducers provided in-line and transrectal imaging. Retrograde urethrography was performed before and after the periurethral treatments. After treatment, the prostates were grossly examined, sectioned, and submitted for histologic examination. In the lateral lobe treatments, a well-demarcated cavity containing liquefied material was present at the ablation site. Microscopically, the targeted volume was characterized by the presence of histotripsy paste (debris, absent cellular structures). A narrow margin of cellular injury was noted, beyond which no tissue damage was apparent. The periurethral treatments resulted in total urethral ablation or significant urethral wall damage, with visible prostatic urethral defects on retrograde urethrography. Real-time ultrasound imaging demonstrated a dynamic hyperechoic zone at the focus, indicative of cavitation and suggesting effective tissue ablation. The results of our study have shown that histotripsy is capable of precise prostatic tissue destruction and results in subcellular fractionation of prostate parenchyma. Histotripsy can also produce prostatic urethral damage and thereby facilitate drainage of finely fractionated material per urethra, producing immediate debulking.


The development of amphids and amphidial glands in adult Syngamus trachea (Nematoda: Syngamidae).
Nematode amphids are a pair of lateral cephalic sense organs, each comprising a group of sensory endings terminating in a cuticle-lined pit. In Syngamus trachea, a parasite of birds, each amphid is surrounded by two non-nervous supporting elements, a large gland cell basally and a smaller supporting cell anteriorly. The amphidial glands display high levels of secretory activity from five to six days postinfection. Secretory material is discharged through the lumen of the sense organ onto host tissue. The ultrastructure of amphids and amphidial glands has been investigated in newly moulted, immature and mature adults to trace the development of glandular activity and its effect on amphid-amphidial gland relationships. In newly moulted adults, the glands have very low levels of secretory activity and appear to act only as supporting cells to the amphids. As secretory activity increases, the gland cell membrane surrounding the sensory endings is elaborated into a reticulum which probably forms the secretory surface. In mature adults the amphid pit is swollen and filled with secretion; the sensory endings are relegated to the periphery of the lumen. It is suggested that amphidial glands develop from typical supporting cells, but acquire a new role possibly associated with parasite attachment.


Gastrointestinal motor patterns: motilin as a coordinating factor.
Our aim was to further define the role of neural and hormonal control of upper gastrointestinal motility patterns. In five dogs, the stomach and duodenum were separated enterically by transecting and oversewing the proximal duodenum and by anastomosing a Roux-en-Y jejunal limb to the pylorus. Five intact dogs served as controls. After recovery, motility was recorded on four or more occasions during fasting and after feeding. Plasma was sampled for motilin radioimmunoassay. In three Roux-en-Y dogs, motilin (0.1 microgram/kg iv) was administered. We found in the Roux-en-Y group that the characteristic MMC occurred in the stomach, duodenum, and jejunal limb, but the jejunal MMC had a much shorter period (P less than 0.005). Gastric and duodenal MMCs were coordinated temporally and were associated with peaks in plasma motilin concentration. Jejunal MMCs had no apparent association with plasma motilin. Feeding disrupted the gastric and duodenal MMC and decreased plasma motilin, but inhibited the jejunal MMC in only 6 of 12 experiments. Exogenous motilin induced a "premature" MMC in the stomach, duodenum, and jejunum. This study suggests that (1) enteric neural continuity and/or luminal continuity are not necessary for coordination of gastric and duodenal motor patterns, and (2) post-prandial inhibition of the duodenal MMC may not depend on the presence of ingested nutrient in the duodenum. Hormonal factors, possibly motilin, may play a role in initiation and coordination of gastric and duodenal motor patterns.


Radiological and clinical characteristics of intussuscepted, inverting, and inverted Meckel's diverticulum: A case series.
Inverted Meckel's diverticulum (IMD) is a well-established but rare disease. This study aimed to summarize the radiological and clinical characteristics of IMD, and correlates its radiological and surgical findings to obtain an accurate early preoperative diagnosis. This is a retrospective study included IMD patients from a large children's medical center in China, between January 2009 and March 2022. We reviewed demographic data, clinical manifestations, preoperative examinations, surgical findings, histopathological results, and outcomes. Twenty-three cases with IMD (14 male patients [60.9%]; median age, 6.7 years; age range, 9 months to 13 years) were retrospectively reviewed over a period of 13 years. The typical clinical manifestations of IMD included abdominal pain, vomiting, and abdominal tenderness. The most commonly used imaging modalities were abdominal ultrasound and computed tomography. This is the first case series on pediatric IMD, that describes the clinical process of IMD, proposes clinical phases of IMD, and first summarizes the radiological findings characteristic of each clinical phase. The clinical process of IMD can be divided into four phases (intussuscepted Meckel's diverticulum [MD], inverting MD, inverted MD, intussusception secondary to IMD). Patients in different clinical phases present with various radiological features. Mastering the radiological and clinical characteristics of each phase of IMD can aid in its early diagnosis and timely operative intervention, thus avoiding unnecessary intestinal necrosis and resection.


QSAR modeling of the antimicrobial activity of peptides as a mathematical function of a sequence of amino acids.
Antimicrobial peptides have emerged as new therapeutic agents for fighting multi-drug-resistant bacteria. However, the process of optimizing peptide antimicrobial activity and specificity using large peptide libraries is both tedious and expensive. Therefore, computational techniques had to be applied for process optimization. In this work, the representation of the molecular structure of peptides (mastoparan analogs) by a sequence of amino acids has been used to establish quantitative structure-activity relationships (QSARs) for their antibacterial activity. The data for the studied peptides were split three times into the training, calibration and test sets. The Monte Carlo method was used as a computational technique for QSAR models calculation. The statistical quality of QSAR for the antibacterial activity of peptides for the external validation set was: n=7, r(2)=0.8067, s=0.248 (split 1); n=6, r(2)=0.8319, s=0.169 (split 2); and n=6, r(2)=0.6996, s=0.297 (split 3). The stated statistical parameters favor the presented QSAR models in comparison to 2D and 3D descriptor based ones. The Monte Carlo method gave a reasonably good prediction for the antibacterial activity of peptides. The statistical quality of the prediction is different for three random splits. However, the predictive potential is reasonably well for all cases. The presented QSAR modeling approach can be an attractive alternative of 3D QSAR at least for the described peptides.


Identification of novel and conserved functional and structural elements of the G1 cyclin Cln3 important for interactions with the CDK Cdc28 in Saccharomyces cerevisiae.
Regions of the budding yeast G1 cyclin Cln3 were characterized using mutational analysis and viability assays to identify functionally relevant and novel mutant alleles of CLN3. Cyclin proteins are conserved, and Cln3 contains a region with homology to the cyclin box, which is thought to mediate physical interactions with the cyclin-dependent kinase. CLN3 was found to have characteristics similar to the conserved cyclin fold found in higher eukaryotic cyclin boxes, which consist of five alpha-helices. Peptide linker sequences inserted within helices 1, 2, 3 and 5 resulted in a loss of Cln3 function, showing cyclin fold structure similar to that previously observed for the G1 cyclin Cln2. A clustered-charge-to-alanine scan mutagenesis revealed two regions of Cln3 important for Cln3-dependent viability. The first region encompasses the conserved cyclin box. The second region is identified with alanine substitutions located well past the cyclin box, just prior to the C-terminal region of Cln3 important for protein stability. Cln3 with mutational changes in each of these regions are expressed at steady-state levels higher than wild-type Cln3, and show some defect in binding to Cdc28. The conserved hydrophobic patch domain (HPD) of cyclins is present within the first helix of the cyclin box. Alanine substitutions introduced into the HPD of Cln3 and Cln2 show functional defects while maintaining physical interaction with Cdc28 as measured by co-immunoprecipitation assay.


(E)-Benzyl 2-{4-[eth-yl(2-hy-droxy-eth-yl)amino]-benzyl-idene}hydrazinecarbodi-thio-ate.
In the title compound, C19H23N3OS2, the dihedral angle between the aromatic rings is 86.80 (8)° and the tertiary amine grouping is almost planar (bond-angle sum at the N atom = 360.0°). In the crystal, pairwise N-H⋯O hydrogen bonds link the mol-ecules into inversion dimers, and O-H⋯S hydrogen bonds link the dimers into [101] chains.


Responses of proximal tubular cells to injury in congenital renal disease: fight or flight.
Most chronic kidney disease in children results from congenital or inherited disorders, which can be studied in mouse models. Following 2 weeks of unilateral ureteral obstruction (UUO) in the adult mouse, nephron loss is due to proximal tubular mitochondrial injury and cell death. In neonatal mice, proximal tubular cell death is delayed beyond 2 weeks of complete UUO, and release of partial UUO allows remodeling of remaining nephrons. Progressive cyst expansion develops in polycystic kidney disease (PKD), a common inherited renal disorder. The polycystic kidney and fibrosis (pcy)-mutant mouse (which develops late-onset PKD) develops thinning of the glomerulotubular junction in parallel with growth of cysts in adulthood. Renal insufficiency in nephropathic cystinosis, a rare inherited renal disorder, results from progressive tubular cystine accumulation. In the Ctns knockout mouse (a model of cystinosis), proximal tubular cells become flattened, with loss of mitochondria and thickening of tubular basement membrane. In each model, persistent obstructive or metabolic stress leads ultimately to the formation of atubular glomeruli. The initial "fight" response (proximal tubular survival) switches to a "flight" response (proximal tubular cell death) with ongoing oxidative injury and mitochondrial damage. Therapies should be directed at reducing proximal tubular mitochondrial oxidative injury to enhance repair and regeneration.


PACAP decides neuronal laminar fate via PKA signaling in the developing cerebral cortex.
Laminar formation in the developing cerebral cortex requires the precisely regulated generation of phenotype-specified neurons. To test the possible involvement of pituitary adenylate cyclase-activating polypeptide (PACAP) in this formation, we investigated the effects of PACAP administered into the telencephalic ventricular space of 13.5-day-old mouse embryos. PACAP partially inhibited the proliferation of cortical progenitors and altered the position and gene-expression profiles of newly generated neurons otherwise expected for layer IV to those of neurons for the deeper layers, V and VI, of the cerebral cortex. The former and latter effects were seen only when the parent progenitor cells were exposed to PACAP in the later and in earlier G1 phase, respectively; and these effects were suppressed by co-treatment with a protein kinase A (PKA) inhibitor. These observations suggest that PACAP participates in the processes forming the neuronal laminas in the developing cortex via the intracellular PKA pathway.


Subunit stoichiometry of the chloroplast photosystem I complex.
A native photosystem I (PS I) complex and a PS I core complex depleted of antenna subunits has been isolated from the uniformly 14C-labeled aquatic higher plant, Lemna. These complexes have been analyzed for their subunit stoichiometry by quantitative sodium dodecyl sulfate-polyacrylamide gel electrophoresis methods. The results for both preparations indicate that one copy of each high molecular mass subunit is present per PS I complex and that a single copy of most low molecular mass subunits is also present. These results suggest that iron-sulfur center X, an early PS I electron acceptor proposed to bind to the high molecular mass subunits, contains a single [4Fe-4S] cluster which is bound to a dimeric structure of high molecular mass subunits, each providing 2 cysteine residues to coordinate this cluster.


The influence of esters and carboxylic acids as the N-substituent of opioids. Part 1: Benzomorphans.
To investigate the effects of carboxylic ester and acid moieties as the N-substituent of opioids, a short series of racemic N-substituted normetazocines was prepared. The introduction of both groups as the normetazocine N-substituent produced compounds which displayed low potency in vitro and in vivo, with the esters displaying the greater activity. The pharmacology of the compounds is discussed with implications resulting from potential in vivo metabolic hydrolysis.


Seronegative hepatitis C virus infection in a child infected via mother-to-child transmission.
Hepatitis C virus (HCV) infection typically leads to antibody response within weeks after primary infection. Here, we describe the case of a child infected with HCV by mother-to-child transmission who remained persistently seronegative despite the presence of high levels of circulating HCV RNA.


The N-terminal tetra-peptide (IPDE) short extension of the U-box motif in rice SPL11 E3 is essential for the interaction with E2 and ubiquitin-ligase activity.
Rice, a monocot model plant, contains at least 77 U-box E3 ubiquitin (Ub)-ligases and 48 E2 Ub-conjugating enzymes. Here, we investigated the minimal binding domain of rice SPL11 U-box E3 to its E2 partners. Serial deletions and site-directed mutagenesis analyses indicated that, in addition to an intact U-box motif, the N-terminal tetra-peptide (IPDE) short extension of the U-box was essential for the interaction of SPL11 with E2s and Ub-ligase activity. The Ile and Pro residues at the -4 and -3 positions of the U-box, respectively, were crucial for this interaction. These results suggest that the N-terminal tetra-peptide extension of the U-box participates in the specific interaction of SPL11 E3 with E2s in a sequence-specific manner in rice.


CDDO-imidazolide mediated inhibition of malignant cell growth in Waldenström macroglobulinemia.
Waldenström macroglobulinemia (WM) is a B-cell malignancy that remains incurable. Synthetic triterpenoids (ST), 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO), its methyl ester derivative (CDDO-Me) and imidazolide derivative (CDDO-Im) induce cell death and inhibit growth of various malignancies and hold promise as treatment for cancer patients. We examined the therapeutic potential of these compounds in WM. All three forms of CDDO induced equal toxicity in BCWM.1 cells. In malignant B cells from WM patients, CDDO-Im induced the greatest toxicity. CDDO-Im inhibited proliferation at nanomolar concentrations and arrested the cells in G0/G1. CDDO-Im induced apoptotic cell death that was partially abolished in the presence of caspase inhibitor. CDDO-Im also inhibited survival pathways that have been shown to be important in WM. Overall, our data suggest that ST are likely to provide therapeutic efficacy for WM patients.


3D Printed lattice microstructures to mimic soft biological materials.
Our group has developed a method for 3D printing mechanically-realistic soft tissue, as a building block towards developing anatomically realistic 3D-printed biomechanical testbed models. A Polyjet 3D printer was used to print lattice microstructures, which were tested in compression to evaluate the elastic profile. Lattice properties including element diameter, element spacing (ES), element cross-sectional geometry, element arrangement, and lattice rotation were varied to determine their effect on the stress-strain curve. As a case study, a single 3D printed sample was tuned such that its elastic profile matched plantar fat. Element diameter and ES had the largest effect on the stress-strain profile, and rotating the lattice microstructure tends to linearize the curves. A simple cubic lattice microstructure of cylindrical elements, with 0.5 mm diameter columns and 1.2 mm spacing had a stress-strain curve the was closest to plantar fat. The elastic modulus at 10, 30, and 50% strain was 7.55, 9.50, and 252 kPa respectively. Physiologic plantar fat at the same strain values has moduli values of 1.08, 7.13, and 188 kPa. We demonstrated that lattice microstructures can decrease the young's modulus of soft 3D printed materials by three orders of magnitude. By creating a method for fine-tuning the elastic profile of 3D-printed materials to behave like human soft tissue, we provide an attractive alternative to more exotic and time-consuming techniques such as molding and casting.


The transmission of information in natural systems.
An isomorphism of information storage and transmission in natural systems is presented. First, a structural and functional dichotomy found in the control centres of the predominant systems in the physical, biological and psychological realms is outlined. The dichotomy of control is shown to allow for an intrinsic balance between the preservation of a system's information, on the one hand, and its alteration and usage, on the other. It is then shown that the mechanisms of communication between the control centre elements are isomorphic among these diverse systems. That is, the transmission of information from one control element to another entails its "double-inversion", which allows for the retrieval of the information in its original form by means of a second transfer process. This mechanism of information transmission leads to novel conclusions concerning the nature of the "brain code".


Kallikrein gene transfer induces angiogenesis and further improves regional cerebral blood flow in the early period after cerebral ischemia/reperfusion in rats.
The aims of this study were to find out whether kallikrein could induce angiogenesis and affect the cerebral blood flow (rCBF) in the early period after cerebral ischemia/reperfusion (CI/R). The adenovirus carried human tissue kallikrein (HTK) gene was administrated into the periinfarction region after CI/R. At 12, 24, and 72 h after treatments, neurological deficits were evaluated; expression of HTK and vascular endothelial growth factor (VEGF) were detected by immunohistochemistry staining; the infarction volume was measured; and rCBF was examined by( 14) C-iodoantipyrine microtracing technique. The expression of VEGF was enhanced significantly in pAdCMV-HTK group than controls over all time points (P < 0.05). Furthermore, the rCBF in pAdCMV-HTK group increased markedly than controls at 24 and 72 h after treatment (P < 0.05), and the improved neurological deficit was accompanied by reduced infarction volume in pAdCMV-HTK group 24 and 72 h posttreatment. In the early period after CI/R, kallikrein could induce the angiogenesis and improve rCBF in periinfarction region, and further reduce the infarction volume and improve the neurological deficits.


Design, synthesis, and evaluation of the self-assembled antimicrobial peptides based on the ovalbumin-derived peptide TK913.
The preparation, self-assembly, and antimicrobial activity of peptides based on TK913 is described. TK9Z4 incorporating a Pro-Pro motif exhibited self-assembly but no cytotoxicity. However, peptide TKZ3 (obtained by changing the amino acid sequence of TK9Z4) showed morphological changes at different concentrations, potent antimicrobial activity, low cytotoxicity, and trypsin resistance. Accordingly, TKZ3 is proposed as new AMP derived from ovalbumin-derived peptides.


Recurrent subacute visual loss presenting in a 52-year-old Caucasian woman with chronic relapsing inflammatory optic neuropathy: a case report.
Chronic relapsing inflammatory optic neuropathy is a recently described form of recurrent isolated subacute optic neuropathy. The condition is highly responsive to systemic steroid treatment and prone to relapse on steroid withdrawal. A complete work up for demyelination, autoimmune disease and sarcoidosis must be made before considering chronic relapsing inflammatory optic neuropathy. We describe the case of a 52-year-old Caucasian woman who presented with isolated subacute optic neuropathy. There was no evidence of demyelination, autoimmunity or sarcoidosis. There was an abrupt and prompt response to systemic corticosteroids and a relapse of the condition on steroid withdrawal. Chronic relapsing inflammatory optic neuropathy requires careful consideration and differentiation from demyelinating optic neuritis and ischemic optic neuropathy since the treatment is different and the outcome without treatment is likely to be poor. The importance of identifying these patients has considerable clinical implications as the condition is highly responsive to steroids.


Immunization of mice against coccidioidomycosis with a subcellular vaccine.
In vitro-cultivated spherules of Coccidioides immitis were disrupted in a Braun homogenizer. The resultant wall fragments were separated from cell sap and endospores by centrifugation. Extraction of the walls with phosphate-buffered saline yielded a subcellular fraction that was immunogenic in mice. This fraction, which contained polysaccharide and protein, gave substantial protection against intranasal challenge with a usually lethal dose (1,000) of arthrospores, provided that it was administered with adjuvant.


Factors influencing successful bone union of isolated subtalar arthrodesis for posttraumatic subtalar arthritis: a multicenter case series.
The purpose of this study was to find the factors influencing successful bone union for isolated subtalar arthrodesis in posttraumatic subtalar arthritis following calcaneal fracture. We retrospectively analyzed the rate of successful bone union of 119 cases of isolated subtalar arthrodesis for posttraumatic subtalar arthritis performed at five university hospitals between January 2010 and December 2019. Multivariate logistic regression analysis was used to find the factors associated with successful bone union. Successful bone union was defined as resolution of hindfoot pain with the presence of osseous trabecular bridging involving more than 50% of the posterior facet within 6 months postoperatively. There were 77 (64.7%) cases of successful bone union, 11 (9.2%) cases of delayed union, 8 (6.7%) cases of questionable union, and 23 (19.3%) cases of nonunion. Use of fully threaded screws was 5.90 times [odds ratio (OR) = 5.90, 95% confidence interval (CI) = 1.42-24.49, p = 0.02] more likely to achieve successful bone union compared to the use of partially threaded screws. Use of two parallel screws or the two divergent screws were 3.71 times (OR = 3.71, 95% CI = 1.05-13.14, p = 0.04) and 4.65 times (OR = 4.65, 95% CI = 1.23-17.53, p = 0.02) more likely to achieve successful bone union compared to the use of a single screw. Use of cancellous autograft or structural autograft was 4.72 times (OR = 4.72, 95% CI = 1.17-19.06, p = 0.03) and 7.12 times (OR = 7.12, 95% CI = 1.46-34.68, p = 0.02) more likely to achieve successful bone union compared to no graft use. Use of fully threaded screws, autograft, and two screws compared to a single screw were the factors associated with successful bone union within six postoperative months after subtalar arthrodesis for the posttraumatic arthritis.


Prevalence of and Factors Associated With Genital and Extragenital Chlamydia and Gonorrhea Among Transgender Women in HIV Care in the United States, 2005 to 2016.
Data on testing rates and prevalence of and factors associated with genital and extragenital chlamydia and gonorrhea among transgender women with HIV in the United States are limited. This retrospective cohort analysis included transgender women living with HIV enrolled in the US Centers for AIDS Research Network of Integrated Clinical Systems cohort between January 2005 and December 2016 with chlamydia or gonorrhea testing performed in HIV clinic. The primary outcome was a positive test result for chlamydia or gonorrhea at urogenital or extragenital (rectal/pharyngeal) sites. Factors associated with infection were examined using logistic regression and generalized estimating equations to account for multiple tests per woman. Among 312 transgender women in HIV care, 252 (81%) were tested for chlamydia or gonorrhea at least once. Annual testing rates were low: 23% to 53% at genital sites and 24% to 47% at extragenital sites. A total of 88 infections were detected, and 22% of women (55/252) had at least one positive test result. Most infections occurred at extragenital sites (80% of chlamydia and 82% of gonorrhea positive test results). Factors associated with infection in an adjusted model were as follows: age 18 to 29 years compared with ≥50 years (adjusted odds ratio [aOR], 7.6; 95% confidence interval [CI], 1.8-31.2), CD4 count >350 compared with CD4 <200 (aOR, 5.5; 95% CI, 1.2-25.1), and higher engagement in HIV care (aOR, 2.2; 95% CI, 1.0-4.5). Among transgender women living with HIV, testing rates for chlamydia and gonorrhea are inadequate, particularly at extragenital sites where most infections occur.


[Increased kidney cell proliferation caused by folic acid treatment after dichromate induced renal failure (author's transl)].
Folic acid is given intravenously to rats 5 to 10 days after a dichromate induced damage of the kidneys. These injection cause an additional damage in the function and structure of the kidneys, but on the other hand, they induce a cell proliferation detected by the increased uptake of thymidine. This cell proliferation in the kidney-tissue seems to be a part of specific reactions to the folic acid.


Forward deviation of the mandibular condyle enhances endochondral ossification of condylar cartilage indicated by increased expression of type X collagen.
Using type X collagen as a marker, this research was designed to examine the alteration of condylar growth in response to mandibular condylar forward positioning. One hundred female Sprague-Dawley rats with 5 weeks of age were randomly divided into five experimental and five control groups. In the experimental groups, bite jumping appliances created forward positioning of the condyle. The experimental rats, together with the age-matched controls, were sacrificed on days 3, 7, 14, 21 and 30, respectively. Tissue sections were cut in the sagittal plane through the mandibular condyle and were processed for in situ hybridization and immunostaining of type X collagen and then for quantitative imaging analyses. (1) Both type X collagen mRNA in situ hybridization signals and type X collagen immunostaining were localized within the hypertrophic zone of the condylar cartilage. (2) With condylar forward positioning, the level of type X collagen mRNA signals (8,541 +/- 74 microm(2) at peak) was 300% higher than that in the controls (2,117 +/- 78 microm(2) at peak); type X collagen immunostaining in condylar advancing groups (54,864 +/- 134 microm(2) at peak) was 254% more than that in the controls (15,470 +/- 121 microm(2) at peak). (3) The amount of type X collagen mRNA signals and immunostaining in experimental and control groups reached the highest levels at day 14 and day 21, respectively, indicating that an increase in endochondral ossification occurred 21 days after condylar forward deviation. Condylar forward repositioning provokes an enhanced maturation of condylar chondrocytes resulting in increased synthesis of type X collagen, a extracellular protein that attributes to endochondral ossification.


Comment on Samulewski et al. Magnetite Synthesis in the Presence of Cyanide or Thiocyanate under Prebiotic Chemistry Conditions. Life 2020, 10, 34.
Samulewski et al. (2020) [...].


Home parenteral nutrition and AIDS.
The evolution of AIDS in 25 patients enrolled in a home parenteral nutrition(HPN) programme was analysed retrospectively. All patients were grade 4C or 4D (CDC criteria). All suffered from major gastrointestinal symptoms, 13 had anorexia (< 700 kcal/day) and the overall mean weight loss was 21%. HPN involved administration of an all-in-one nutritional formula (caloric intake = 148% of MREE) which was infused at night through a Broviac type silastic catheter or a subcutaneous infusion port. It was continued until the patient's death or temporary recovery. 19 patients died during PN, 4 showed a temporary stabilisation. The average duration of PN was 180 days (54-358). Because of rehospitalizations for opportunistic infections or PN complications, the mean time spent at home was only 101 days (13-296), or 58.5% of the total duration of PN. 21 patients experienced weight gain and the Karnofsky activity index increased in half the patients. A temporary return to work was possible in only 3 patients. 15 PN related septicaemias were diagnosed for 4400 days of PN (0.34 for 100 days). On the whole, HPN seems to have been beneficial in 13 out of 25 patients, but the criteria for identifying patients who are likely to respond are not clearly established.


Effect of race on longitudinal central hemodynamics in pregnancy.
To compare central hemodynamics between white, black and Asian women in pregnancy. This was a prospective, longitudinal study of maternal central hemodynamics in white, black and Asian women with a singleton pregnancy, assessed using a bioreactance method at 11 + 0 to 13 + 6, 19 + 0 to 24 + 0, 30 + 0 to 34 + 0 and 35 + 0 to 37 + 0 weeks' gestation. At each visit, cardiac output (CO), stroke volume (SV), heart rate (HR), peripheral vascular resistance (PVR) and mean arterial pressure were recorded. Multilevel linear mixed-effects analysis was performed to compare the repeated measures of the cardiac variables between white, black and Asian women, controlling for maternal characteristics, medical history and medication use. The study population included 1165 white, 247 black and 116 Asian women. CO increased with gestational age to a peak at 32 weeks and then decreased; the highest CO was observed in white women and the lowest in Asian women. SV initially increased after the first visit but subsequently declined with gestational age in white women, decreased with gestational age in black women and remained static in Asian women. In all three study groups, HR increased with gestational age until 32 weeks and then remained constant; HR was highest in black women and lowest in white women. PVR showed a reversed pattern to that of CO; the highest values were in Asian women and the lowest in white women. The least favorable hemodynamic profile, which was observed in black and Asian women, was reflected in higher rates of a small-for-gestational-age infant. There are race-specific differences in maternal cardiac adaptation to pregnancy. White women have the most favorable cardiac adaptation by increasing SV and HR, achieving the highest CO and lowest PVR. In contrast, black and Asian women have lower CO and higher PVR than do white women, with CO increasing through a rise in HR due to declining or static SV. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.


Assembly of the inhibitory glycine receptor: identification of amino acid sequence motifs governing subunit stoichiometry.
The inhibitory glycine receptor (GlyR) is a pentameric protein composed of two types (alpha and beta) of membrane-spanning subunits. Coexpression in Xenopus oocytes of a low affinity mutant of the alpha 2 subunit with the alpha 1 and beta subunits indicated that GlyRs assembled from alpha 1 and alpha 2 polypeptides contain variable subunit ratios, whereas alpha/beta hetero-oligomers have an invariant (3:2) stoichiometry. Analysis of different alpha/beta chimeric constructs revealed that this difference in assembly behavior is mediated by the N-terminal extracellular regions of the receptor subunits. Substitution of residues diverging between the alpha and beta subunits identified combinations of sequence motifs determining subunit stoichiometry.


Single cell laser light scattering spectroscopy in a flow cell: repeated sickling of sickle red blood cells.
We performed dynamic laser light scattering measurements of hemoglobin aggregates in single, sickle erythrocytes. Sickle erythrocytes were attached to the poly-(L-lysine)-coated surface of a flow cell. They were exposed to several oxygenation-deoxygenation cycles by repeatedly changing the flowing solution. The rate of cycling was found to be a determining factor for the formation of irreversible morphologic alterations as well as irreversible hemoglobin aggregates. In slow cycling, the sickle erythrocytes took an irreversible, irregular, rounded shape, and hemoglobin aggregates were observed even in the oxygenated state after 20 cycles. In the fast cycling, however, these changes did not take place even after 60 cycles.


Gene expression alteration during redox-dependent enhancement of arsenic cytotoxicity by emodin in HeLa cells.
Emodin (1,3,8-trihydroxy-6-methylanthraquinone) could enhance the sensitivity of tumor cells to arsenic trioxide (As2O3)-induced apoptosis via generation of ROS, but the molecular mechanism has not been elucidated. Here, we carried out cDNA microarray-based global transcription profiling of HeLa cells in response to As2O3/emodin cotreatment, comparing with As2O3-only treatment. The results showed that the expression of a number of genes was substantially altered at two time points. These genes are involved in different aspects of cell function. In addition to redox regulation and apoptosis, ROS affect genes encoding proteins associated with cell signaling, organelle functions, cell cycle, cytoskeleton, etc. These data suggest that based on the cytotoxicity of As2O3, emodin mobilize every genomic resource through which the As2O3-induced apoptosis is facilitated.


Differentiation of amylase isozyme in amniotic fluid with fetal age.
Composition of the amylase isozymes in the amniotic fluid and their transition with fetal age were studied by means of thin-layer acrylamide gel electrophoresis. The results indicate that amylase isozymes in the amniotic fluid were composed of a pancreatic type faint major isozyme and several salivary type isozymes consisting of an intense major and a few less intense minor bands. Characteristic changes in the pattern of these isozymes with fetal age consisted of a marked increase of the salivary type isozymes rather than of the pancreatic type isozyme. A densitometric analysis of the isozyme patterns proved that the ratio of the pancreatic type isozyme to the salivary type major isozyme was highly correlated with fetal age regardless of levels of amylase activity.


The effect of current passage on N-methyl-D-aspartate-induced, tetrodotoxin-resistant membrane potential oscillations in lamprey neurons active during locomotion.
In lamprey spinal cord neurons, N-methyl-aspartate (NMA) can elicit tetrodotoxin (TTX)-resistant membrane potential oscillations (10-25 mV), that are of similar frequency to those recorded during NMA-induced fictive locomotion before TTX. The frequency of the oscillations was progressively reduced when increasing the amount of hyperpolarizing DC current. Brief de- or hyperpolarizing pulses gave phase-dependent effects on the duration of the oscillation cycle and rhythm resetting. Periodic stimuli could entrain the oscillatory activity. Under normal conditions, these oscillations will be influenced by synaptic activity, leading to an adequate coordination between neurons active during locomotion.


Biodistribution and brain permeability of the extracellular domain of neuregulin-1-β1.
Neuregulin-1 (NRG1) belongs to a large family of growth and differentiation factors with a key role in the development and maintenance of the brain. Genetic association of NRG1 within brain disorders such as Alzheimer's disease, schizophrenia and neuroprotective properties of certain NRG1 isoforms have led to a variety of studies in corresponding disease models. In the present work, we investigated NRG1 with regard to its peripheral and central biodistribution after systemic application. We first-time radiolabeled the entire biologically active extracellular domain of NRG1 isotype-β1 (NRG1-β1 ECD; aa 2-246) with iodine-125 and administered it peripherally to healthy adult C57Bl6 mice. Blood kinetics and relative organ distribution of (125)I-labeled NRG1-β1 ECD were determined. The blood level of NRG1-β1 ECD peaked within the first hour after intraperitoneal (i.p.) application. The brain-blood ratios of (125)I-labeled NRG1-β1 ECD were time-dependently 150-370% higher compared to the brain impermeable control, (131)I-labeled bovine serum albumin. Autoradiographs of brain slices demonstrated that (125)I-labeled NRG1-β1 ECD accumulated in several regions of the brain e.g. frontal cortex, striatum and ventral midbrain containing the substantia nigra. In addition we found histochemical and biochemical evidence that phosphorylation of the NRG1 prototype receptor ErbB4 was increased in these regions after systemic application of NRG1-β1 ECD. Our data suggest that NRG1-β1 ECD passes the blood-brain barrier and activates cerebral ErbB4 receptors.


Artificial selection in the expansion of rice cultivation.
Gene distributions and population genomics suggest artificial selection of ghd7 osprr37, for extremely early heading date of rice, in the Tohoku region of Japan. The ranges of cultivated crops expanded into various environmental conditions around the world after their domestication. Hokkaido, Japan, lies at the northern limit of cultivation of rice, which originated in the tropics. Novel genotypes for extremely early heading date in Hokkaido are controlled by loss-of-function of both Grain number, plant height and heading date 7 (Ghd7) and Oryza sativa Pseudo-Response Regulator 37 (OsPRR37). We traced genotypes for extremely early heading date and analyzed the phylogeny of rice varieties grown historically in Japan. The mutations in Ghd7 and OsPRR37 had distinct local distributions. Population genomics revealed that varieties collected from the Tohoku region of northern Japan formed three clusters. Mutant alleles of Ghd7 and OsPRR37 appear to have allowed rice cultivation to spread into Hokkaido. Our results show that the mutations of two genes might be occurred in the process of artificial selection during early rice cultivation in the Tohoku region.


Palaeotempestology: the study of prehistoric tropical cyclones--a review and implications for hazard assessment.
Records of prehistoric tropical cyclones occur in the form of ridges of coral rubble, sand, shell, sand and shell, and pumice; erosional terraces in raised gravel beaches; barrier washover deposits; and, sediments deposited in the shallow offshore marine environment. Other less well-documented records occur as variations in isotopic ratios within speleothems and possibly tree rings, and changes in pollen records resulting from introduction of new species after forest disturbance due to cyclonic winds. As yet, such records have not been identified beyond 5500 years of age. Recent palaeotempestological studies in the United States and northern Australia have highlighted that the frequency and magnitude of these natural hazards do not remain constant over time, and there are periods when cyclogenesis is enhanced, and others of relative quiescence. Recognition of such regime changes, or non-stationarity in the long-term record, is important for risk assessments of this hazard. Until now however, few if any risk assessments have incorporated data from the long-term record of tropical cyclones, and instead have relied on generally short instrumented historical records. The longer-term records suggest that such an approach may miscalculate the 1% Annual Exceedance Probability risk to coastal communities from future tropical cyclones.


Nodular lymphocyte-predominant Hodgkin lymphoma: cytopathologic correlates on fine-needle aspiration.
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL), a rare subtype of Hodgkin lymphoma, is an indolent tumor with frequent instances of disease recurrence but a favorable prognosis. To the best of the authors' knowledge, there are only limited descriptions of NLPHL in the cytology literature because it was only formally recognized as a distinct entity in 1994. In the current study, all cases of NLPHL diagnosed on excisional biopsy (n = 6 cases) at the study institution between 2000 and 2011 that had undergone previous fine-needle aspiration (FNA) were reviewed, with a focus on cytomorphologic features. Four of 6 cases were termed benign on FNA; however, there was retrospective recognition of characteristic LP cells in all cases. Unlike classical Hodgkin lymphoma, the tumor cells of NLPHL were often found to be mononucleate and presented in a background of small lymphocytes. Other features identified included epithelioid histiocytes and numerous bare atypical nuclei. Cases of NLPHL are commonly misdiagnosed as benign reactive lymphoid tissue and therefore a careful search using high magnification for LP cells is recommended in the evaluation of lymph node FNAs.


Comparison of concentration methods for rapid detection of hookworm ova in wastewater matrices using quantitative PCR.
Hookworm infection contributes around 700 million infections worldwide especially in developing nations due to increased use of wastewater for crop production. The effective recovery of hookworm ova from wastewater matrices is difficult due to their low concentrations and heterogeneous distribution. In this study, we compared the recovery rates of (i) four rapid hookworm ova concentration methods from municipal wastewater, and (ii) two concentration methods from sludge samples. Ancylostoma caninum ova were used as surrogate for human hookworm (Ancylostoma duodenale and Necator americanus). Known concentration of A. caninum hookworm ova were seeded into wastewater (treated and raw) and sludge samples collected from two wastewater treatment plants (WWTPs) in Brisbane and Perth, Australia. The A. caninum ova were concentrated from treated and raw wastewater samples using centrifugation (Method A), hollow fiber ultrafiltration (HFUF) (Method B), filtration (Method C) and flotation (Method D) methods. For sludge samples, flotation (Method E) and direct DNA extraction (Method F) methods were used. Among the four methods tested, filtration (Method C) method was able to recover higher concentrations of A. caninum ova consistently from treated wastewater (39-50%) and raw wastewater (7.1-12%) samples collected from both WWTPs. The remaining methods (Methods A, B and D) yielded variable recovery rate ranging from 0.2 to 40% for treated and raw wastewater samples. The recovery rates for sludge samples were poor (0.02-4.7), although, Method F (direct DNA extraction) provided 1-2 orders of magnitude higher recovery rate than Method E (flotation). Based on our results it can be concluded that the recovery rates of hookworm ova from wastewater matrices, especially sludge samples, can be poor and highly variable. Therefore, choice of concentration method is vital for the sensitive detection of hookworm ova in wastewater matrices.


Endotracheal Intubation Strategy, Success, and Adverse Events Among Emergency Department Patients During the COVID-19 Pandemic.
To describe endotracheal intubation practices in emergency departments by staff intubating patients early in the coronavirus disease 2019 (COVID-19) pandemic. Multicenter prospective cohort study of endotracheal intubations conducted at 20 US academic emergency departments from May to December 2020, stratified by known or suspected COVID-19 status. We used multivariable regression to measure the association between intubation strategy, COVID-19 known or suspected status, first-pass success, and adverse events. There were 3,435 unique emergency department endotracheal intubations by 586 participating physicians or advanced practice providers; 565 (18%) patients were known or suspected of having COVID-19 at the time of endotracheal intubation. Compared with patients not known or suspected of COVID-19, endotracheal intubations of patients with known or suspected COVID-19 were more often performed using video laryngoscopy (88% versus 82%, difference 6.3%; 95% confidence interval [CI], 3.0% to 9.6%) and passive nasal oxygenation (44% versus 39%, difference 5.1%; 95% CI, 0.9% to 9.3%). First-pass success was not different between those who were and were not known or suspected of COVID-19 (87% versus 86%, difference 0.6%; 95% CI, -2.4% to 3.6%). Adjusting for patient characteristics and procedure factors in those with low anticipated airway difficulty (n=2,374), adverse events (most commonly hypoxia) occurred more frequently in patients with known or suspected COVID-19 (35% versus 19%, adjusted odds ratio 2.4; 95% CI, 1.7 to 3.3). Compared with patients not known or suspected of COVID-19, endotracheal intubation of those confirmed or suspected to have COVID-19 was associated with a similar first-pass intubation success rate but higher risk-adjusted adverse events.


Conceptual change and preschoolers' theory of mind: evidence from load-force adaptation.
Prominent theories of preschoolers' theory of mind development have included a central role for changing or adapting existing conceptual structures in response to experiences. Because of the relatively protracted timetable of theory of mind development, it has been difficult to test this assumption about the role of adaptation directly. To gain evidence that cognitive adaptation is particularly important for theory of mind development, we sought to determine whether individual differences in cognitive adaptation in a non-social domain predicted preschoolers' theory of mind development. Twenty-five preschoolers were tested on batteries of theory of mind tasks, executive functioning tasks, and on their ability to adapt their lifting behavior to smoothly lift an unexpectedly heavy object. Results showed that children who adapted their lifting behavior more rapidly performed better on theory of mind tasks than those who adapted more slowly. These findings held up when age and performance on the executive functioning battery were statistically controlled. Although preliminary, we argue that this relation is attributable to individual differences in children's domain general abilities to efficiently change existing conceptual structures in response to experience.


Sn-Beta zeolites with borate salts catalyse the epimerization of carbohydrates via an intramolecular carbon shift.
Carbohydrate epimerization is an essential technology for the widespread production of rare sugars. In contrast to other enzymes, most epimerases are only active on sugars substituted with phosphate or nucleotide groups, thus drastically restricting their use. Here we show that Sn-Beta zeolite in the presence of sodium tetraborate catalyses the selective epimerization of aldoses in aqueous media. Specifically, a 5 wt% aldose (for example, glucose, xylose or arabinose) solution with a 4:1 aldose:sodium tetraborate molar ratio reacted with catalytic amounts of Sn-Beta yields near-equilibrium epimerization product distributions. The reaction proceeds by way of a 1,2 carbon shift wherein the bond between C-2 and C-3 is cleaved and a new bond between C-1 and C-3 is formed, with C-1 moving to the C-2 position with an inverted configuration. This work provides a general method of performing carbohydrate epimerizations that surmounts the main disadvantages of current enzymatic and inorganic processes.


Genomic analysis of lignocellulolytic enzyme producing novel Streptomyces sp.MS2A for the bioethanol applications.
The conversion of lignocellulosic waste to energy offers a cost-effective biofuel. The current study discusses the utilization of cellulose in rice husks by lichen-associated Streptomyces sp. MS2A via carbohydrate metabolism. Out of 39 actinobacteria, one actinobacterial strain MS2A, showed CMCase, FPase, and cellobiohydrolase activity. The whole genome analysis of Streptomyces sp. MS2A showed maximum similarity with Streptomyces sp. CCM_MD2014. The genome analysis confirmed the presence of cellulose-degrading genes along with xylan-degrading genes that code for GH3, GH6, GH9, GH11, GH43, GH51, and 15 other GH families with glycosyl transferase, carbohydrate-binding modules, and energy metabolism groups. Protein family analysis corroborates the enzyme family. Among the 19,402 genes of Streptomyces sp. MS2A, approximately 70 GH family codes for lignocellulose degradation enzymes. The structure of cellulase was modeled and validated. Scanning electron microscopy and gas chromatography-mass spectrometry (GCMS) was performed to analyze the lignocellulosic degradation of rice husk and the end product bioethanol.


Pregnancy following gastric bypass surgery for morbid obesity: maternal and neonatal outcomes.
The purpose of this study was to compare obstetric and neonatal outcomes after Roux-en-Y gastric bypass (RYGB) to those in women without such surgery. Women with RYGB (cases) were matched for maternal age and prior cesarean to the next two consecutive women delivering without prior bariatric surgery (controls). Pregnancy and newborn outcomes were compared by univariate analysis. Outcomes approaching or reaching statistical significance were evaluated by conditional logistic regression controlling for maternal body mass index (BMI). Despite gastric bypass, the 38 cases were heavier (BMI 33.4+/-7.3 vs. 28.1+/-6.7 kg/m2, p<0.001) and more often obese (BMI> or =30 kg/m2, 26/38 (68.4%) vs. 20/76 (26.3%), p<0.001) than controls. Variables evaluated by logistic regression adjusted for BMI did not differ in cases versus controls, including hypertension (odds ratio [OR] 2.62, 95% confidence interval [CI] 0.66-10.50), preterm premature rupture of membranes (OR 0.24, 95% CI 0.02-3.38), oligohydramnios (OR 2.39, 95% CI 0.66-8.61), and delivery > or =41 weeks (OR 0.57, 95% CI 0.11-2.97). Obstetric and neonatal outcomes after RYGB are similar to those of our general obstetric population.


Hijacking host components for bacterial biofilm formation: An advanced mechanism.
Biofilm is a community of bacteria embedded in the extracellular matrix that accounts for 80% of bacterial infections. Biofilm enables bacterial cells to provide particular conditions and produce virulence determinants in response to the unavailability of micronutrients and local oxygen, resulting in their resistance to various antibacterial agents. Besides, the human immune reactions are not completely competent in the elimination of biofilm. Most importantly, the growing body of evidence shows that some bacterial spp. use a variety of mechanisms by which hijack the host components to form biofilm. In this regard, host components, such as DNA, hyaluronan, collagen, fibronectin, mucin, oligosaccharide moieties, filamentous polymers (F-actin), plasma, platelets, keratin, sialic acid, laminin, vitronectin, C3- and C4- binding proteins, antibody, proteases, factor I, factor H, and acidic proline-rich proteins have been reviewed. Hence, the characterization of interactions between bacterial biofilm and the host would be critical to effectively address biofilm-associated infections. In this paper, we review the latest information on the hijacking of host factors by bacteria to form biofilm.


Multiple detectors "Influence Method".
The "Influence Method" is conceived for the absolute determination of a nuclear particle flux in the absence of known detector efficiency and without the need to register coincidences of any kind. This method exploits the influence of the presence of one detector in the count rate of another detector, when they are placed one behind the other and define statistical estimators for the absolute number of incident particles and for the efficiency (Rios and Mayer, 2015a). Its detailed mathematical description was recently published (Rios and Mayer, 2015b) and its practical implementation in the measurement of a moderated neutron flux arising from an isotopic neutron source was exemplified in (Rios and Mayer, 2016). With the objective of further reducing the measurement uncertainties, in this article we extend the method for the case of multiple detectors placed one behind the other. The new estimators for the number of particles and the detection efficiency are herein derived.


Liquid chromatography-tandem mass spectrometric assay for the mutated BRAF inhibitor vemurafenib in human and mouse plasma.
A bioanalytical assay for the mutated BRAF inhibitor vemurafenib was developed and validated. For the quantitative assay, human plasma samples were pre-treated using protein precipitation with water-acetonitrile (1/3, v/v) containing sorafenib as internal standard. The extract was directly injected into the chromatographic system. This system consisted of a sub-2 μm particle, trifunctional bonded octadecyl silica column with isocratic elution using 0.01% (v/v) of formic acid in a mixture of water and methanol. The eluate was transferred into the electrospray interface with positive ionization and the analyte was detected in the selected reaction monitoring mode of a triple quadrupole mass spectrometer. The assay was validated in a 0.1-100 μg/ml calibration range. Within day precisions were 1.6-3.2%, between day precisions 2.7% and 8.2% and accuracies were between 99% and 106% for the whole calibration range. The drug was stable under all relevant conditions. Finally, the assay was successfully used to assess drug levels in a pharmacokinetic mouse study.


Doxorubicin inhibits human DNA topoisomerase I.
Purified human DNA topoisomerase I was assayed quantitatively by enzyme titrations with supercoiled pHC624 DNA in the presence of 0-2.0 microM doxorubicin. Supercoiled and relaxed DNAs were resolved by agarose gel electrophoresis in the presence of ethidium bromide, and the percentage of conversion of supercoiled DNA to relaxed DNA was quantified by scanning microdensitometry. The inhibition of DNA topoisomerase I activity was measured at varying concentrations of doxorubicin. Doxorubicin inhibited enzyme activity at an IC50 value (the concentration required to inhibit 50% of the total activity) of 0.8 microM. Similar inhibition was observed for daunomycin, a structurally related anthracycline antitumor drug. These results indicate that anthracyclines inhibit human DNA topoisomerase I activity at concentrations that cause DNA damage and cytotoxicity in vivo.


Reuterin in the healthy gut microbiome suppresses colorectal cancer growth through altering redox balance.
Microbial dysbiosis is a colorectal cancer (CRC) hallmark and contributes to inflammation, tumor growth, and therapy response. Gut microbes signal via metabolites, but how the metabolites impact CRC is largely unknown. We interrogated fecal metabolites associated with mouse models of colon tumorigenesis with varying mutational load. We find that microbial metabolites from healthy mice or humans are growth-repressive, and this response is attenuated in mice and patients with CRC. Microbial profiling reveals that Lactobacillus reuteri and its metabolite, reuterin, are downregulated in mouse and human CRC. Reuterin alters redox balance, and reduces proliferation and survival in colon cancer cells. Reuterin induces selective protein oxidation and inhibits ribosomal biogenesis and protein translation. Exogenous Lactobacillus reuteri restricts colon tumor growth, increases tumor reactive oxygen species, and decreases protein translation in vivo. Our findings indicate that a healthy microbiome and specifically, Lactobacillus reuteri, is protective against CRC through microbial metabolite exchange.


Utilization patterns of extended-release niacin in Canada: analysis of an administrative claims database.
To evaluate utilization patterns with extended-release niacin (ERN) compared with those observed with other lipid-modifying drugs (LMDs). A random sample of 17% of patients who had at least one LMD dispensation between January 2004 and February 2007 was obtained from the administrative databases of the Régie de l'assurance maladie du Quebec. Primary outcomes included drug adherence, persistence and discontinuation with ERN and other LMDs, and daily maintenance dose attainment (1500 mg and 2000 mg) with ERN at one-year follow-up. Adherence was defined as the sum of days of all dispensations divided by the total number of days of follow-up. Persistence was defined as renewal of prescription before the end of dispensation plus a grace period (50% prescription duration). Among 26,862 patients, the majority received statins (73.4%), whereas 867 (3.2%) received ERN. The mean age of ERN patients was 62 years and 75% were male. After one year, adherence with ERN was below that of statins (62.0% versus 74.9%), as was persistence (36.1% versus 46.7%), while discontinuation rates were higher (64.0% versus 53.3%). The median time until discontinuation for ERN was shorter than for statins (66 days versus 99 days). After one year, 5.8% of patients were taking 1500 mg or more and 3.2% were on 2000 mg. In the present cohort of patients from regular clinical practice in Quebec, ERN use was associated with low prescription rates, inferior adherence and persistence compared with other LMDs, high discontinuation rates, and very low 2000 mg dose attainment.


Diagnosis of amitraz resistance in Brazilian populations of Rhipicephalus (Boophilus) microplus (Acari: Ixodidae) with larval immersion test.
Among the ectoparasites of cattle, Rhipicephalus (Boophilus) microplus (Canestrini) (Acari: Ixodidae) remains a major cause of economic losses to livestock. The chemical control with acaricides is still the most efficient method available to control ticks. The aims of this study were to diagnose resistance to amitraz in 16 tick populations from the States of São Paulo (14) and Paraná (2), using the larval immersion technique (LIT), and evaluate the effect of synergists [piperonyl butoxide (PBO), diethyl maleate (DEM), triphenyl phosphate (TPP)] on amitraz resistant and susceptible strains of cattle tick. Most of the evaluated populations (68.7 %) showed to be resistant to amitraz, with resistance ratios ranging from 2.14 to 132. The results suggest that the test procedure by LIT is sensitive and adequate for detection and monitoring of amitraz resistance in cattle tick. No synergistic effect was observed for the synergists PBO, DEM and TPP, on the amitraz resistant (Poa) strain of cattle tick, indicating that increased detoxification metabolism was not involved in this resistance.


In-hospital outcomes of PCI in patients who have ESRD vs non-ESRD patients, a retrospective study involving a National Inpatient Sample (NIS) database.
Cardiovascular disease is the leading cause of death for patients with end-stage renal disease (ESRD). ESRD is known to affect a large portion of the American population. Previous data for patients undergoing percutaneous coronary intervention (PCI) in the setting of ESRD for Acute Coronary Syndrome (ACS) and non-ACS etiologies have shown to have an increase in in-hospital mortality, and prolonged hospitalization among other complications. The national inpatient sample (NIS) was used to identify patients who underwent PCI between the years 2016-2019. Patients were then grouped into those with ESRD on renal replacement therapy (RRT). Logistic regression models were employed to assess the primary outcome of in-hospital mortality, while linear regression models were utilized to evaluate secondary outcomes, including hospitalization cost and length of stay. A total of 21,366 unweighted observations were initially included, consisting of 50 % ESRD patients and 50 % randomly selected patients without ESRD who underwent PCI. These observations were weighted to represent a national estimate of 106,830 patients. The mean age of the study population was 65 years, and 63 % of the patients were male. The ESRD group had a greater representation of minority groups compared to the control group. The in-hospital mortality rate was significantly higher in the ESRD group compared to the control group, with an odds ratio of 1.803 (95 % CI: 1.502 to 2.164; p-value of 0.0002). Additionally, the ESRD group had significantly higher healthcare costs and longer length of stay, with a mean difference of $47,618 (95 % CI: $42,701 to $52,534, p-value <0.0001) and 2.933 days (95 % CI, 2.729 to 3.138 days, p-value <0.0001), respectively. In-hospital mortality, cost, and length of stay for patients undergoing PCI were found to be significantly greater in the ESRD group.


Clinical features of chronic hepatitis B patients with lean nonalcoholic fatty liver disease.
The clinical features have been well described in obese chronic hepatitis B (CHB) patients with nonalcoholic fatty liver disease (NAFLD). However, little is known about the clinical features of lean CHB-NAFLD patients. The study retrospectively included treatment-naïve CHB patients who underwent ultrasound between 2015 and 2021. Liver fibrosis was assessed by aspartate aminotransferase (AST) to platelet ratio index (APRI), Fibrosis-4 score (FIB-4), NAFLD fibrosis score (NFS), and transient elastography. Among 1226 CHB-NAFLD patients, 25.0% patients were lean. The age, gender, and platelet, alanine aminotransferase, AST, and albumin levels were comparable between lean CHB-NAFLD and nonlean patients. The levels of plasma glucose, triglycerides, total cholesterol, and uric acid, as well as proportions of concurrent hypertension and diabetes, were lower in lean patients. Lean patients presented higher hepatitis B surface antigen (HBsAg) levels (3.4 log10 IU/ml vs. 3.2 log10 IU/ml, p = 0.006), hepatitis B virus (HBV) DNA levels (4.1 log10 IU/ml vs. 3.2 log10 IU/ml, p < 0.001), and hepatitis B e antigen (HBeAg) positive proportions (40.4% vs. 30.2%, p = 0.002) than nonlean patients. The values of APRI, FIB-4, and liver stiffness were comparable between two groups. However, lean patients had lower NFS values (-3.0 vs. -2.6, p < 0.001) and lower proportions (12.6% vs. 21.1%, p = 0.003) of advanced fibrosis (NFS ≥ -1.5) than nonlean patients. Similar results were observed in HBeAg-positive and HBeAg-negative subgroups. Nearly a quarter of CHB-NAFLD patients were lean. Lean patients had lower proportions of metabolic abnormalities and advanced liver fibrosis than nonlean patients. However, lean CHB-NAFLD patients had higher HBsAg levels, HBV DNA levels, and HBeAg-positive proportions. Registry and registration no. of the study/trial: Clinicaltrials.gov, Identifier: NCT03097952.


[Long-term outcome of patients with renal transplant and neural tube defect].
To evaluate the long term outcome of renal transplant in patients with a neural tube defect causing voiding dysfunctions. Between 1993 and 2010, 18 cadaveric renal transplants were performed in 16 patients (5 females and 11 males) older than 15 years with a neural tube defect and voiding dysfunction. The patients had dialysis since the mean age of 27.4 and have been transplanted at the mean age of 32.2. The survival rate of the first kidney transplant was 93.75% at 1 year and 63.3% at 5 and 10 years respectively. With a mean follow-up of 6.67 years, 11 out of 16 first transplants remained functional (68.75%) The median survival of the first transplants was 13.52 years. At the end of the follow-up, 13 out of 18 transplants were still functional (72.2%). The mean serum creatinine level was 123.9 micromol/l with a mean glomerular filtration rate estimated by the simplified MDRD formula of 67 ml/min for the 13 still functional transplants. Before transplantation, 66% of patients had a neuro-urologic assessment versus 100% thereafter. Renal transplantation in patients with neural tube defect is feasible without surgical particularities to those of other renal failure causes. These type of patients represented less than 1% of the followed cohort with an average graft survival rate of 63.3% at five and 10 years. The median survival time of the first graft was 13.52 years.


Cross-cultural differences and similarities in nurses' experiences during the early stages of COVID-19 in Korea and the United States: A qualitative descriptive study.
At the onset of the COVID-19 pandemic, governmental responses varied worldwide, which resulted in healthcare professionals and organizations having different experiences. As threats of global infectious disease and disasters increase, it is important to examine the collective experiences of nurses to leverage support across international settings and systems and to tailor specific policies to their local nursing workforce. To compare and contrast nurses' experiences working in hospitals at the onset of COVID-19 in South Korea and the United States. This was a qualitative descriptive study. Nurses in South Korea and the United States were recruited through social media using snowball sampling between April and May 2020. Semi-structured telephone interviews were audio-recorded, transcribed, and translated as needed. The transcripts were analyzed thematically, and each theme was compared and synthesized using NVivo 12. A total of 43 nurses from South Korea (n = 21) and the United States (n = 22) participated in the study. The majority of the participants were female and working as staff nurses in both countries. The work settings were similar between the participants from two countries. However, the participants in South Korea provided less direct care to patients with COVID-19 compared to the participants in the United States. Despite cultural and infrastructure differences, the nurses shared similar experiences. The overlapping similarities of nurses' experience highlight the need for national and global policies for a safe work environment and psychological well-being. The differences between the two countries also emphasize that specific policies and practice implications for the local contexts are needed in addition to global policies.