Adverse pregnancy outcomes in healthcare workers: a Korean nationwide population-based study.
To assess female healthcare workers' pregnancy complications and outcomes including abortion, fetal screening abnormalities, intrauterine growth retardation (IUGR), and preterm labor using nationwide population data and compare these results with those of the general population in Korea. Korean National Health Insurance (NHI) claim data was used. We choose 3 different reference groups for comparison: (1) dependents of employees insured by NHI, i.e. non-working women, (2) all insured employees, i.e. all working women, and (3) workers in the education division. To compare the groups, logistic regression was used for multivariate analysis after adjusting for age and income level. Overall, healthcare workers showed a higher adjusted OR (odds ratio) in almost all obstetrical consequences. Miscarriage, threatened abortion, preterm labor, fetal screening abnormalities, and IUGR showed a higher adjusted OR in the working group than in the non-working group. We also observed similar results in a comparison of both the working groups. Regarding workers in the education division, ORs for obstetrical outcomes were also high, except for preterm labor. Health care workers have a higher risk of adverse pregnancy outcomes such as miscarriage, IUGR, and fetal screening abnormalities.


Survival and function in patients with tumours of the head and neck operated on and reconstructed with free flaps.
From 1983 to 2003, 131 patients were operated on in the head and neck region with 139 free flaps. They were operated on using a team approach of ear, nose, and throat surgeons and plastic surgeons, and sometimes maxillofacial surgeons. The tumours were squamous cell carcinoma (SCC) 104 (80%), salivary gland cancer 13 (10%), sarcoma 5 (4%), basal cell carcinoma 4 (3%), and others 4 (3%). The staging of the primary intraoral SCC tumours (n=79) was 42% in stage II, 28% in stage III, and 30% in stage IV. The survival of patients with primary oral SCC was compared with a previously treated previous series that gave an increase in tumour-related five-year survival from 48% to 58%. Most flaps were radial forearm flaps (73%). Fifteen percent were vascularised bone transfers. A questionnaire was sent to patients who had had oral/oropharyngeal tumours to measure function and satisfaction, to which 47/49 responded. The results including ability to chew and swallow; speech was good, with a median score of 0.78 (range 1-0).


Antifungal activities of actinomycete strains associated with high-altitude sagebrush rhizosphere.
The antifungal-producing potential of actinomycete populations from the rhizosphere of low-altitude sagebrush, Artemisia tridentata, has been examined. In a continued investigation of new sources of antifungal-producing microorganisms, this study examined the antifungal-producing potential of actinomycetes from the rhizosphere of high-altitude A. tridentata. With high-altitude sagebrush, rhizosphere soil actinomycete numbers were one to four orders of magnitude higher than those found in nonrhizosphere bulk soils and different from those found with the low-altitude plants. A total of 122 actinomycete isolates was screened against nine fungal species and six bacterial species for the production of antimicrobial compounds. Four rhizosphere isolates, Streptomyces amakusaensis, S. coeruleorubidus, S. hawaiiensis and S. scabies, showed broad-spectrum antifungal activity against three or more fungal species in plate assays. In liquid antagonism assays, mycelium production by Aspergillus niger was reduced by up to 50% by two of the actinomycete isolates. These results demonstrate the potential of rhizosphere microbiology in the search for new antimicrobials.


Vibrational circular dichroism signature of hemiprotonated intercalated four-stranded i-DNA.
The four-stranded intercalated DNA structure exemplified by the oligonucleotide 5'-d(CCCCCCCCCCCC) (d(C)12) was studied at acidic pH by infrared absorption (IR) and vibrational circular dichroism (VCD) spectroscopy and compared with spectra of the same oligonucleotide at neutral pH to establish distinct VCD markers for the intercalation motif. The most striking feature is a new absorption at 1694 cm(-1) and its corresponding VCD couplet with reversed sign. These are unique for the intercalated structure and have not been observed for other parallel stranded duplexes. Significant characteristic features resulting from the spatial arrangement of the sugar-phosphate backbone are also clearly present for d(C)12 at acidic pH. An extensive network of CH...O bonds twists the backbone such that multiple through-space vibrational coupling occurs among neighbouring sugar-phosphate residues resulting in unusual VCD signals.


Origin of Th17 Cells in Type 2 Diabetes-Potentiated Periodontal Disease.
New strategies are critically needed to counter uncontrolled periodontal infection and inflammation in obesity-associated type 2 diabetes (T2D). However, mechanisms that explain the relationship between periodontitis (PD) and T2D remain poorly understood. Several lines of evidence indicate that destructive immune responses potentiate periodontitis (PD) in T2D. B cells are abundant in periodontal lesions, and our data show that B cells are required for PD in obese/insulin resistant but not lean/normoglycemic mice. In mice and in people, T2D-primed B cells supported Th17 cytokine profiles, but B cells had a modest effect on T-cell function in samples from normoglycemic individuals. Given the recently appreciated importance of Th17 cells in PD outside a T2D milieu, our data raise the possibility that B cells indirectly promote T2D-potentiated PD through support of Th17 cells, which in turn directly promote PD.Data herein thereby suggest unexpected mechanisms that explain the clinical observation that T2D potentiates PD.


Tibial plateau fractures treated with the less invasive stabilisation system.
Thirty-six tibial plateau fractures in 35 patients were treated with the less invasive stabilisation system (LISS). Patients' mean age was 42 years. There were 27 type C fractures and nine type B fractures according to AO/OTA classification. The average time to healing was 4.2 months (3-7 months). Deep infection developed in two cases. One patient healed in 6 degrees of varus, and seven patients had an increased articular angulation of 6 degrees (4-8 degrees ) in the sagittal plane. There were no cases of loss of reduction, non-union, or deep vein thrombosis. The LISS system could be considered for the management of tibial plateau fractures.


[A majority of useless call of an on-call urology resident: a study of the AFUF].
To assess the workload of an on-call urology resident at a French University Hospital. A prospective study was performed during 15 days in February 2012. The data recorded in our database regarded the resident (sex, age, time to go to work), the call (emergency, type and reason) and the person who called (grade, department). Seven centres including 18 residents participated. On average five calls were received per day [0-17]. After midnight, the resident was called less than twice (1.6). There was an actual emergency in 64% of cases [0-13]. The urology-related call motives (73%) mainly consisted in acute urine retention (AUR) and catheter problems (73), renal colic (RC) (49), acute pyelonephritis (23), and hematuria (22). Residents had to go to the hospital in 55% of AUR and catheter problems, 30% of acute pyelonephritis, 17% of RC and 14% of hematuria. The emergency department (ED) called the urology resident in 39% of cases but only 18% required the presence of the resident. A call made by a senior was more likely to be an emergency (67%) than by a resident or a nurse (51%, P=0.02). The urology resident when on-call is mainly asked for an advice by the ED. Among urology-related advice, bladder catheterization problems were the most frequent. RC was the second call motive but most of the time was not an actual emergency.


The punctate midline myelotomy concept for visceral cancer pain control--case report and review of the literature.
Nauta et al. first reported on a successful punctate midline myelotomy (PMM) at the spinal cord Th 10 level for the treatment of intractable pelvic cancer pain. The authors published another case history of a patient with multiple anaplastic carcinomas of the small intestine, peritoneal carcinosis and retroperitoneal lymphomas, suffering from severe visceral pain in the hypo-, meso-, and epigastrium. Nauta's PMM was successfully performed at the level Th 4. Narcotic medication was tapered from 30 mg i.v. morphine per hour preoperatively to 5 mg per hour within 5 days postoperatively. Pain intensity decreased from 10 to 2-3 on the visual analog scale. Only minor transient side effects appeared postoperatively. Pain reduction remained until the patient died from the extended disease five weeks later. Meanwhile Nauta et al. reported on 5 additional patients, in whom PMM led to a sufficient pain reduction. Another paper reported on sufficient control of visceral pain due to advanced stomach cancer after a modified Th 1-2 PMM. PMM sufficiently controls not only pelvic visceral pain, but also visceral pain generated in the meso- and epigastrium. The findings support the concept of a midline dorsal column visceral pain pathway.


Nature of hardness evolution in nanocrystalline NiTi shape memory alloys during solid-state phase transition.
Due to a distinct nature of thermomechanical smart materials' reaction to applied loads, a revolutionary approach is needed to measure the hardness and to understand its size effect for pseudoelastic NiTi shape memory alloys (SMAs) during the solid-state phase transition. Spherical hardness is increased with depths during the phase transition in NiTi SMAs. This behaviour is contrary to the decrease in the hardness of NiTi SMAs with depths using sharp tips and the depth-insensitive hardness of traditional metallic alloys using spherical tips. In contrast with the common dislocation theory for the hardness measurement, the nature of NiTi SMAs' hardness is explained by the balance between the interface and the bulk energy of phase transformed SMAs. Contrary to the energy balance in the indentation zone using sharp tips, the interface energy was numerically shown to be less dominant than the bulk energy of the phase transition zone using spherical tips.


Investigation of the antimicrobial activities of Snakin-Z, a new cationic peptide derived from Zizyphus jujuba fruits.
Snakin-Z is a novel antimicrobial peptide (AMP) that is identified from the fruit of Zizyphus jujuba. This peptide is composed of 31 amino acids which is determined with the sequence of CARLNCVPKGTSGNTETCPCYASLHSCRKYG and molecular weight of 3318.82 Da. Snakin-Z is not identical to any AMP in the peptide database. According to this study, Snakin-Z potentially has antimicrobial property against bacteria and fungi. Minimal inhibitory concentration (MIC) value of this peptide is suitable for antimicrobial activity. We assessed that Snakin-Z could affect Phomopsis azadirachtae with the MIC value of 7.65 μg/mL and vice versa Staphylococcus aureus with the MIC value of 28.8 μg/mL. Interestingly, human red blood cells also showed good tolerance to the Snakin-Z. On the basis of this study, Snakin-Z can be an appropriate candidate for therapeutic applications in the future due to its antimicrobial property.


Eco-friendly and green synthesis of silver nanoparticles using leaf extract of Strychnos potatorum Linn.F. and their bactericidal activities.
Inspired green synthesis of metallic nanoparticles is evolving as an important branch of nanotechnology. Traditionally these are manufactured by wet chemical methods which require toxic and flammable chemicals. We report for the first time an economic and eco-friendly green synthesis of silver nanoparticles using Strychnos potatorum aqueous leaf extract from 3 mM silver nitrate solution. Nanoparticles thus formed are confirmed and characterized by using UV-Vis absorption spectroscopy, SEM and XRD measurements. The XRD and SEM analysis showed the average particle size of nanoparticles as 28 nm as well as revealed their (mixed, i.e., cubic and hexagonal) structure. Further, these green synthesized nanoparticles showed bactericidal activity against multidrug-resistant human pathogenic bacteria.


Increasing duration of circulatory arrest, but not antegrade cerebral perfusion, prolongs postoperative recovery after neonatal cardiac surgery.
Deep hypothermic circulatory arrest (DHCA) and antegrade cerebral perfusion (ACP) are 2 cardiopulmonary bypass techniques applied in aortic arch repair. In recent literature, cerebral effects of both techniques have received most attention, whereas the consequences for other organs have not been thoroughly investigated. Therefore, in this study, the impact of duration of DHCA and ACP on postoperative recovery was analyzed in a cohort of neonates undergoing aortic arch reconstruction. All consecutive neonates who underwent aortic arch reconstruction from 2004 to 2009 were included in this retrospective study. Length of stay on the intensive care unit (ICU-LOS), duration of mechanical ventilation, inotrope score, and areas under the curve (AUC) for lactate and creatinine were compared with respect to durations of DHCA and ACP, respectively. Correction for confounders was performed using multivariable linear regression. Eighty-three neonates were included, with a 30-day mortality of 4.8%. Longer duration of DHCA was associated with longer ICU-LOS both in univariable and multivariable analyses. Similarly, duration of mechanical ventilation and lactate and creatinine AUCs increased with duration of DHCA. Inotrope score was only associated with DHCA duration in univariable analysis. Duration of ACP did not affect any of the outcome parameters. Increasing duration of DHCA, but not ACP, during neonatal aortic arch reconstruction prolongs short-term postoperative recovery. This suggests all efforts should be made to reduce the duration of DHCA to the shortest period possible, which may be achieved by exclusive use of ACP or a combination of the 2 perfusion techniques.


Synthesis, preclinical evaluation, and first-in-human study of Al18F-PSMA-Q for prostate cancer imaging.
To investigate the potential of a novel Al18F-labeled PSMA-targeted radiotracer for PCa diagnosis through both preclinical and pilot clinical studies. Al18F-PSMA-Q was prepared automatically. The binding affinity to PSMA was evaluated in vitro using the 22Rv1 (PSMA +) and PC-3 (PSMA -) cell lines. Pharmacokinetics evaluation, biodistribution study, Micro-PET imaging of Al18F-PSMA-Q in normal mice and tumor-bearing mice, and a comparison with 18F-DCFPyL were performed. PET/CT imaging was performed on 8 healthy volunteers and 20 newly diagnosed PCa patients at 1 h post-injection (p.i.). The biodistribution in human and preliminary diagnostic efficacy of Al18F-PSMA-Q were evaluated, and the radiation dosimetry was estimated using OLINDA/EXM 2.0 software. Qualified Al18F-PSMA-Q was efficiently prepared with a non-decay-corrected radiochemical yield (RCY) of 22.0-28.3%, a specific activity (SA) of > 50 GBq/μmol. The hydrophilicity was comparably high with a log P value of - 3.69 ± 0.39. Al18F-PSMA-Q was found to bind to PSMA specifically with a Ki value of 17.05 ± 1.14 nM. The distribution and elimination half-lives of Al18F-PSMA-Q were 3.93 min and 14.22 min, respectively, which were shorter than those of 18F-DCFPyL. Micro-PET imaging of Al18F-PSMA-Q can clearly differentiate 22Rv1 tumors from PC-3 tumors and background with a high SUVmax of 2.17 ± 0.42 and a tumor-to-muscle ratio of 84.37 ± 31.62, which were higher than those of 18F-DCFPyL (1.79 ± 0.39 and 13.25 ± 1.65). The uptake of Al18F-PSMA-Q in 22Rv1 cells and tumors can be substantially blocked by 2-PMPA. High level accumulation of Al18F-PSMA-Q was observed in organs physiologically expressing PSMA. Twenty-six tumor lesions were detected in 20 PCa patients, and the mean SUVmax values of primary tumors, lymph node metastasis, bone metastases, and tumor-muscle ratios were 19.71 ± 16.52, 5.11, 31.30 ± 29.85, and 44.77 ± 22.29, respectively. The mean SUVmax of tumors in patients with PSA > 10 ng/mL was significantly higher than that in patients with PSA ≤ 10 ng/mL (25.97 ± 18.64 vs. 10.33 ± 3.74). Meanwhile, the mean SUVmax of tumors in patients with a Gleason score ≥ 8 was significantly higher than that in patients with a Gleason score < 8 (31.85 ± 22.09 vs. 13.18 ± 11.58). The kidneys received the highest estimated dose of 0.098 ± 0.006 mGy/MBq, and the effective dose was calculated as 0.0128 ± 0.007 mGy/MBq. The novel qualified PSMA-targeted radiotracer Al18F-PSMA-Q was conveniently prepared with favorable yield and SA. The results of preclinical and pilot clinical studies exhibited a high specific uptake in PCa lesions and an excellent tumor-to-background ratio with a reasonable radiation exposure, which indicated the great potential of Al18F-PSMA-Q for PCa imaging. Chinese Clinical trial registry ChiCTR2100053507, Registered 23 November 2021, retrospectively registered.


A variant of ornithine aminotransferase from mouse small intestine.
The ornithine aminotransferase (OAT) activity of mouse was found to be highest in the small intestine. The mitochondrial OAT from mouse small intestine was purified to homogeneity by the procedures including heart treatment, ammonium sulfate fractionation, octyl-Sepharose chromatography, and Sephadex G-150 gel filtration. Comparing to the amino acid sequence of mouse hepatic OAT, six N-terminal amino acid residues have been deleted in intestinal OAT. However, the subsequent sequence was identical with that of hepatic OAT. The molecular weights of both intestinal and hepatic OAT were estimated as 46 kDa by SDS-gel electrophoresis and as 92 kDa by gel filtration, indicating that both native OATs are dimeric. Biochemical properties of intestinal OAT, such as molecular weight, pH optimum and K(m) values for L-ornithine and alpha-ketoglutarate, were similar to those of hepatic OAT. However, intestinal OAT was more labile than hepatic OAT to tryptic digestion.


Temperature-dependent refractive index issues using a UV-visible detector in high-performance liquid chromatography.
While studying the properties of some potential, UV-detection compatible, mobile phase modifiers for reversed-phase liquid chromatography (RPLC) we encountered serious detector baseline problems. The most severe problem was a periodic saw-tooth-shaped drift. This drift was most noticeable when using water-THF and water-dioxolane mobile phases. We demonstrate that the baseline problems are related to temperature fluctuation in a water bath used to maintain a constant column temperature. The temperature fluctuations change the refractive index (RI) of the mobile phase, which in turn affects the amount of light reaching the detector. Our results show that the magnitude of the baseline drift is related to the RI value of the mobile phases. The baseline problems can be alleviated using a different temperature controller whose feedback mechanism assures smoother operation. Since there is no single and complete source of information in the literature concerning the RI values of typical mobile phases in RPLC, we decided to measure them as a function of the % modifier (between 0 and 100%) and the temperature (between 25 degrees C and 50 degrees C). Knowing the RI values allows us to calculate the excess volume of a binary liquid system.


Synthesis and antiinflammatory/analgesic activities of N-heterocyclic carboxamides of thiopyrano-1,2-benzothiazine.
We report the synthesis of N-heterocyclic carboxamides of 5-methyl-4-oxo-2,3,4,5-tetrahydrothiopyrano [3,2-c][1,2]benzothiazine 6,6-dioxide, their antiinflammatory and analgesic activities and the attempts to obtain a corresponding sulfoxidate series. Compounds (II c) and (II l) showed a good antiinflammatory activity which is comparable to that of piroxicam. No compound showed any significant analgesic activity.


Efficacy and safety of a new medicated nail hydrolacquer in the treatment of adults with toenail onychomycosis: A randomised clinical trial.
A new water-soluble formulation with ciclopirox has shown a higher penetration than other ciclopirox nail lacquers currently marketed, thus providing a higher concentration of ciclopirox into the nail. To evaluate the efficacy and safety of a new ciclopirox nail hydrolacquer compared with its vehicle and an active comparator (hydroxypropyl chitosan-based 80 mg/g ciclopirox nail lacquer) for the treatment of toenail fungal infection. Phase III, multicenter, randomised, double-blind, clinical trial in patients with distal mild to moderate toenail onychomycosis due to dermatophyte fungi. Patients were randomised to apply topically a ciclopirox nail hydrolacquer, its vehicle or a reference product once daily for 48 weeks with a follow-up period of 4 weeks up to week 52. A total of 381 patients were included. No statistically significant differences were observed between patient groups in the proportion of subjects achieving a complete cure. At week 52, a higher percentage of patients in the ciclopirox nail hydrolacquer group achieved a mycological cure (negative for culture and DTS/KOH test, with results: 32.0% ciclopirox nail hydrolacquer, 23.2% vehicle and 27% reference product, respectively), and similar results were found for improvement (mycological cure and reduction of diseased nail ≥20%, with results: 27.2% ciclopirox nail hydrolacquer, 21.6% vehicle and 20.6% reference product, respectively). Regarding mycological results, only ciclopirox nail hydrolacquer demonstrated significant statistical superiority versus vehicle negativizing dermatophyte culture (p = .039) with no recurrences, relapses or re-infections in a four-week follow-up patients with complete cure. The safety profile was comparable to the vehicle and reference product and consistent with the previously reported. A new water-soluble formulation for a ciclopirox nail lacquer showed similar efficacy to the reference product to eradicate toenail onychomycosis and superiority in the mycological cure defined by negative culture, thus preventing reinfections and recurrences. Efficacy and safety data demonstrate the positive benefit-risk profile of this new topical antifungal preparation. [Correction added on 13 April 2023, after first online publication: The results and conclusions in the Abstract contained incorrect information and were revised in this version.].


Src family kinases Fyn and Lyn are constitutively activated and mediate plasmacytoid dendritic cell responses.
Plasmacytoid dendritic cells (pDC) are type I interferon-producing cells with critical functions in a number of human illnesses; however, their molecular regulation is incompletely understood. Here we show the role of Src family kinases (SFK) in mouse and human pDCs. pDCs express Fyn and Lyn and their activating residues are phosphorylated both before and after Toll-like receptor (TLR) stimulation. Fyn or Lyn genetic ablation as well as treatment with SFK inhibitors ablate pDC (but not conventional DC) responses both in vitro and in vivo. Inhibition of SFK activity not only alters TLR-ligand localization and inhibits downstream signalling events, but, independent of ex-vivo TLR stimulation, also affects constitutive phosphorylation of BCAP, an adaptor protein bridging PI3K and TLR pathways. Our data identify Fyn and Lyn as important factors that promote pDC responses, describe the mechanisms involved and highlight a tonic SFK-mediated signalling that precedes pathogen encounter, raising the possibility that small molecules targeting SFKs could modulate pDC responses in human diseases.


Extrastriatal Accumulation of 18 F-FP-CIT at Cerebral Infarction in a Patient With Suspected Parkinson Disease.
18 F-FP-CIT PET/CT is a useful diagnostic tool for differentiating between idiopathic Parkinson disease and atypical Parkinson syndrome by visualizing the striatum, where the nerve endings of nigrostriatal dopaminergic neurons are located. We present an unusual accumulation of 18 F-FP-CIT in the infarct and peri-infarct brain area of an 83-year-old man who was referred for the management of suspected cerebral infarction due to sudden dysarthria and delirium.


Do levels of immunoglobulin G antibodies to foods predict the development of immunoglobulin E antibodies to cat, dog and/or mite?
In children at high risk of inhalation allergy, food sensitization is associated with an increased risk for sensitization to inhalant allergens. Furthermore, this association was also found in a cross-sectional study. To examine in a prospective study, whether levels of IgG to foods (i.e. mixture of wheat and rice, mixture of soy bean and peanut, egg white, cow's milk, meat, orange and potato) indicate an increased risk for the future development of IgE antibodies to inhalant allergens in a low-risk population and whether they can be used as predictors of the subsequent development of IgE antibodies in young, initially IgE-negative children. Coughing children, aged 1-5, visiting their GPs, were tested for IgE antibodies to mite, dog and cat (RAST) and IgG (ELISA) to foods. All IgE-negative children were retested for IgE antibodies after two years. The IgG results (66 percentiles) of the first blood sample were compared to the RAST-scores of the second blood sample. After two years, 51 out of 397 (12.8%) originally IgE-negative children, had become IgE-positive for cat, dog and/or mite. An increased IgG antibody level to wheat-rice (OR = 2.2) and to orange (OR = 2.0) indicated an increased risk of developing IgE to cat, dog or mite allergens. In addition to IgG to a mixture of wheat-rice and orange; total IgE, breastfeeding, eczema as a baby and age were the most important predictors for the subsequent development of IgE to inhalant allergens. An increased IgG antibody level to a mixture of wheat-rice or orange, indicates an increased risk of developing IgE to cat, dog or mite allergens. This indicates that excessive activity of the mucosal immune system is present before IgE antibodies to airborne allergens can be demonstrated. Nevertheless, IgG to foods is not very helpful (with a positive predictive value of 16.5%, and negative predictive value of 90.6%) in identifying individual children at risk in clinical practice. However, besides other risk factors, IgG to wheat-rice and to orange could be useful as a screening test for studies in the early identification, i.e. before IgE antibodies can be detected, of children with an increased risk of developing IgE antibodies in the future.


Dose-response effects of a novel fat emulsion (Olibra) on energy and macronutrient intakes up to 36 h post-consumption.
To investigate the dose-response effects of a novel fat emulsion (Olibra) on energy and macronutrient intakes up to 36 h post-consumption in non-overweight subjects. A single-blind, placebo-controlled, within-subject cross-over design was used. Metabolic suite of the University of Ulster, Coleraine. Fifty subjects (30 female, 20 male) from the student and staff population of the University of Ulster, Coleraine. Subjects were given in random order, 7 days apart, a 200 g portion of yoghurt containing a total of 15 g of fat, which varied in quantity of Olibra fat (0, 2, 4, 6 g) at 09:00 h. At 13:00 h subjects were given ad libitum access to a range of foods. Amounts of food consumed were measured by covert pre- and post-consumption weighing of individual serving dishes. For the remainder of the day and the following 24 h, subjects weighed and recorded all food intakes. Relative to the control yoghurt, mean energy (7.42 vs 5.83, 5.60, 5.24 MJ), fat (97.4 vs 74.4, 74.2, 67.5 g; 48.8 vs 46.8, 48.9, 47.6% energy), protein (59.1 vs 50.0, 44.0, 40.8 g; 13.2 vs 13.9, 12.9, 12.8% energy), and carbohydrate (171.5 vs 140.9, 130.2, 126.0 g; 38.0 vs 39.3, 38.2, 39.6% energy), intakes were progressively reduced with increasing doses of Olibra fat in the total group (P<0.001). A similar response was observed in the female group up to 4 g (P<0.001) and in the male group after 2 and 6 g (P<0.05). Energy and macronutrient intakes for the remainder of each study day and over the following 24 h were significantly lower after all dose levels compared to the control (P<0.001). The results suggest that Olibra fat reduced the effect of overeating during an ad libitum lunch meal and subsequent food intake up to 36 h post-consumption.


A systematic review on predicting PV system parameters using machine learning.
Due to the growing demand, assessing performance has become obligatory for photovoltaic (PV) energy harvesting systems. Performance assessment involves estimating different PV system parameters. Traditional ways, such as calculating solar radiation using satellite data and the IV characteristics approach as assessment methods, are no longer reliable enough to provide a reasonable projection of PV system parameters. Estimating system parameters using machine learning (ML) approaches has become a reliable and popular method because of its speed and accuracy. This paper systematically reviewed ML-based PV parameter estimation studies published in the last three years (2020 - 2022). Studies were analyzed using several criteria, including ML algorithm, outcome, experimental setup, sample data size, and error metric. The analysis revealed several interesting factors. The neural network was the most popular ML method (32.55%), followed by random vector functional link (13.95%) and support vector machine (9.30%). Dataset was sourced from hardware tests and computer-based simulations: 66% of the studies used data from only computer simulation, 18% used data from only hardware setup, and the 16% experiments used data from both hardware and simulations to evaluate different system parameters. The top three most commonly used error metrics were root mean square error (29.1%), mean absolute error (17.5%), and coefficient of determination (15.9%). Our systematic review will help researchers assess ML algorithms' projection in PV system parameters estimation. Consequently, scopes shall be created to establish more robust governmental frameworks, expand private financing in the PV industry, and optimize PV system parameters.


The mechanism of sensory transduction in the sensilla of the trochanteral hair plate of the cockroach, Periplaneta americana.
The trochanteral hair plate of the cockroach leg contains approximately 60 hair sensilla that are deflected by a joint membrane during flexion of the leg. Previous work has shown that the organ is a mechanoreceptor which limits leg flexion during walking by reflex connections to flexor and extensor motoneurons. Functional analysis of the largest sensilla has shown that their behaviour may be well approximated by a velocity detector followed by a unidirectional rectifier. We report here the results of an examination of the largest sensilla by scanning and transmission electron microscopy in an attempt to correlate the structure with the known functional elements. Each hair is innervated by a single sensory dendrite which is surrounded by an electron dense dendritic sheath. The dendrite terminates below the hair shaft in a tubular body containing a parallel array of microtubules embedded in an electron dense matrix, while the dendritic sheath extends beyond the tubular body to form the walls of the ecdysial canal. At the proximal end of the tubular body the dendritic sheath and sensory dendrite are anchored to the cuticular socket by a fibrous dome which seems to form a flucrum around which the tubular body can be deflected by movements of the hair. We suggest that the basis for the detection of velocity shealth and the tubular body. The structure is also discussed with relation to the mechanism of sensory transduction and the possible causes of the unidirectional sensitivity.


Use of social media to assess the effectiveness of vagal nerve stimulation in Dravet syndrome: A caregiver's perspective.
Dravet syndrome (DS) is a rare genetic epilepsy syndrome which is particularly pharmacoresistant. Vagus nerve stimulation (VNS) is commonly used in the treatment of DS as an adjunct to medical therapy. A meaningful assessment of post-surgical outcomes with VNS is difficult given the rarity of the condition. In a novel approach, we used social media to contact patients with DS to gather data on post-surgical seizure reduction and overall satisfaction with VNS. A survey consisting of 10 questions was posted to a social media webpage for a DS support group moderated by the Dravet Syndrome Foundation. The results were analyzed and percentages reported using the integrated SurveyMonkey analytical software. 49 responses were received. We found that 28.5% of patients had a >50% reduction in seizure frequency after VNS placement, 55.8% felt that VNS therapy had helped to reduce seizure frequency, and 83.7% felt that seizure severity had improved. Of the respondents, 75% felt that they would undergo VNS implantation again for similar outcomes. We employed the novel technique of using social media to gather the largest set of self-reported outcomes of VNS therapy for Dravet syndrome. As corroborated by prior studies of VNS effectiveness in Dravet syndrome, there is significant albeit limited improvement in seizure control. Our study shows that despite this limitation, it is still considered a useful treatment adjunct from a caregiver's perspective.


Comprehensive lipid and metabolite profiling of children with and without familial hypercholesterolemia: A cross-sectional study.
Individuals with familial hypercholesterolemia (FH) have elevated low-density lipoprotein cholesterol (LDL-C), accelerated atherosclerosis, and premature cardiovascular disease. Whereas children with lifestyle-induced dyslipidemias often present with complex lipid abnormalities, children with FH have isolated hypercholesterolemia. However, to the best of our knowledge, a comprehensive profiling of FH children is lacking. Therefore, we aimed to characterize the lipid-related and metabolic alterations associated with elevated LDL-C in children with FH and healthy children. We measured plasma metabolites in children with FH (n = 47) and in healthy children (n = 57) using a high-throughput nuclear magnetic resonance (NMR) spectroscopy platform, and compared the differences between FH and healthy children. Both statin treated (n = 17) and non-statin treated FH children (n = 30) had higher levels of atherogenic ApoB-containing lipoproteins and lipids, and lipid fractions in lipoprotein subclasses, compared to healthy children (n = 57). FH children displayed alterations in HDL particle concentration and lipid content, compared with healthy children. Interestingly, the small HDL particles were characterized by higher content of cholesteryl esters, and lower levels of free cholesterol and phospholipids. Furthermore, plasma fatty acids were higher in non-statin treated FH children, particularly linoleic acid. Finally, acetoacetate and acetate were lower in FH children compared with healthy children. Hypercholesterolemia in children associates with diverse metabolic repercussions and is more complex than previously believed. In particular, we found that hypercholesterolemia in FH children was paralleled not only by increased atherogenic ApoB-containing lipoproteins and lipid fractions, but also alterations in HDL subfractions that suggest impaired reverse cholesterol transport.


Corrigendum: Chrysophanol Relieves Cisplatin-Induced Nephrotoxicity via Concomitant Inhibition of Oxidative Stress, Apoptosis, and Inflammation.
[This corrects the article DOI: 10.3389/fphys.2021.706359.].


[A study on the relationship between the changes of salivary EGF and oromaxillofacial tumors].
To investigate the relationship between the changes of salivary epidermal growth factor (sEGF) concentration and oromaxillofacial tumors so as to find out its potential clinical value. The saliva of 123 patients with oromaxillofacial tumors,inflammations and precancerous lesions were measured for EGF concentration by radioimmunoassay (RIA) with the ligand(125)I-EGF and the saliva of 40 normal adults as the control. Compared with the control, sEGF level of malignant,benign salivary gland tumors increased obviously;the former is higher than the latter significantly. The sEGF levels of patients with squamous cell carcinoma (SCC) of mucosa,recurrence and precancerous lesion were significantly higher than that of the control. There was no significant difference among the groups,but there was a tendency to increase by degrees. Compared with the control,the increase of the sEGF level of SCC patients with lymph node metastasis was of no significance. The sEGF level of oromaxillofacial inflammation was significantly higher than that of control. The sEGF levels in patients with salivary gland tumor,SCC,inflammation increased in different degrees.


Dual interventional approach of endoscopic reboring in completely stenosed rectal anastomosis using radiology guidance: a novel technique.
Rectal stricture/stenosis is a well-recognized complication following anterior resection. Completely stenosed rectal anastomoses have been conventionally treated conservatively with permanent stoma. The surgical alternatives are either a redo low resection with its accompanying hazards or formation of a permanent colostomy. We describe a simple method of treating anastomotic stenoses using a novel technique in patients with a defunctioned bowel. Three patients with complete stenosis of a rectal anastomosis following anterior resection underwent this novel technique with informed consent. A stenosis with no identifiable lumen was diagnosed at the time of examination under anaesthetic (EUA) or by contrast enema. Using a novel technique of combined endoscopic and radiology guidance, the anastomotic stenosis was rebored and subsequently dilated to restore bowel continuity. There were no complications observed following this procedure. Two of the three patients needed repeat endoscopic dilatation. All patients had restoration of the lumen in the anastomosis and subsequently underwent closure of ileostomy and made an uneventful recovery. Combined endoscopic dilatation under radiological guidance is a novel technique and appears to be a simple, safe, effective and inexpensive method for treating rectal anastomotic stenoses.


Microsomal redox systems in brown adipose tissue: high lipid peroxidation, low cholesterol biosynthesis and no detectable cytochrome P-450.
The presence of redox systems in microsomes of brown adipose tissue (BAT) in cold exposed rats was investigated and compared with liver. BAT microsomes showed high activity of lipid peroxidation measured both by the formation of malondialdehyde (MDA) and by oxygen uptake. NADH and NADPH dependent cytochrome c reductase activity were present in both BAT and liver microsomes. Aminopyrine demethylase and aniline hydroxylase activities, the characteristic detoxification enzymes in liver microsomes could not be detected in BAT microsomes. BAT minces showed very poor incorporation of [1-14C]acetate and [2-14C]mevalonate in unsaponifiable lipid fraction compared to liver. Biosynthesis of cholesterol and ubiquinone, but not fatty acids, and the activity of 3-hydroxy-3-methyl glutaryl CoA reductase appear to be very low in BAT. Examination of difference spectra showed the presence of only cytochrome b5 in BAT microsomes. In addition to the inability to detect the enzyme activities dependent on cytochrome P-450, a protein with the characteristic spectrum, molecular size in SDS-PAGE and interaction with antibodies in double diffusion test, also could not be detected in BAT microsomes. The high activity of lipid peroxidation in microsomes, being associated with large oxygen uptake and oxidation of NADPH, will also contribute to the energy dissipation as heat in BAT, considered important in thermogenesis.


No miRNA were found in Plasmodium and the ones identified in erythrocytes could not be correlated with infection.
The transcriptional regulation of Plasmodium during its complex life cycle requires sequential activation and/or repression of different genetic programmes. MicroRNAs (miRNAs) are a highly conserved class of non-coding RNAs that are important in regulating diverse cellular functions by sequence-specific inhibition of gene expression. What is know about double-stranded RNA-mediated gene silencing (RNAi) and posttranscriptional gene silencing (PTGS) in Plasmodium parasites entice us to speculate whether miRNAs can also function in Plasmodium-infected RBCs. Of 132 small RNA sequences, no Plasmodium-specific miRNAs have been found. However, a human miRNA, miR-451, was highly expressed, comprising approximately one third of the total identified miRNAs. Further analysis of miR-451 expression and malaria infection showed no association between the accumulation of miR-451 in Plasmodium falciparum-iRBCs, the life cycle stage of P. falciparum in the erythrocyte, or of P. berghei in mice. Moreover, treatment with an antisense oligonucleotide to miR-451 had no significant effect on the growth of the erythrocytic-stage P. falciparum. Short RNAs from a mixed-stage of P. falciparum-iRBC were separated in a denaturing polyacrylamide gel and cloned into T vectors to create a cDNA library. Individual clones were then sequenced and further analysed by bioinformatics prediction to discover probable miRNAs in P. falciparum-iRBC. The association between miR-451 expression and the parasite were analysed by Northern blotting and antisense oligonucleotide (ASO) of miR-451. These results contribute to eliminate the probability of miRNAs in P. falciparum. The absence of miRNA in P. falciparum could be correlated with absence of argonaute/dicer genes. In addition, the miR-451 accumulation in Plasmodium-infected RBCs is independent of parasite infection. Its accumulation might be only the residual of erythroid differentiation or a component to maintain the normal function of mature RBCs.


Clinical implications of new studies in the treatment of benign, potentially malignant and malignant ventricular arrhythmias.
For purposes of clinical management, ventricular arrhythmias have been divided into risk categories of benign, prognostically important (potentially malignant) and malignant. Benign arrhythmias occur in the setting of structurally normal hearts and do not require therapy unless associated with debilitating symptoms. Malignant arrhythmias such as sustained ventricular tachycardia or fibrillation deserve aggressive therapy to prevent recurrence. Arrhythmias occurring in the presence of organic heart disease (often ischemic disease) are frequently asymptomatic but prognostically important as a risk factor for sudden death or cardiac arrest. The common empiric practice to treat such arrhythmias (by about 40 to 50% of cardiologists in the United States) needs to be reassessed in the face of the Cardiac Arrhythmia Suppression Trial. For malignant arrhythmias, class IA agents (procainamide and quinidine) continue to be the standard of treatment, and class IB agents (e.g., mexiletine) may be used as alternative or additive therapy. Class IC agents are used as second-line therapy, especially in the setting of ischemic heart disease. Class III therapy with amiodarone is reserved for refractory patients because of potential toxicity. Sotalol, a new class II-III agent, may become a first-line drug. For prognostically important arrhythmias, beta blockers remain the agents of choice, class IC agents are contraindicated, and class IA or IB drugs, or both, should be used conservatively (i.e., only for symptomatic arrhythmias). For symptomatic but benign arrhythmias requiring treatment, beta blockers are safe although not always effective. Class IA, IB and IC agents may then be considered. In these patients, the proarrhythmic potential of quinidine and class IC agents remains a concern.(ABSTRACT TRUNCATED AT 250 WORDS)


[Radiotherapy of patients with stage III Hodgkin's disease using the method of continuous fractionated irradiation].
Clinical rationale for alternating split-course radiotherapy for stage III Hodgkin's disease is discussed. The procedure was employed in 54 such patients. It proved useful in total nodal irradiation for advanced disease, resulting in improved survival. The technique involves a shorter duration of treatment than that of the standard one.


Basic principles and practical steps in the management of fluid balance in the newborn.
The fluid management of newborn babies can pose many problems. This article discusses the factors that affect fluid balance in the newborn infant, both term and preterm, and the special circumstances of the surgical neonate. The main determinants of management are: (1) an estimation of transepidermal water losses; (2) an awareness of glomerular filtration rate and how this is influenced by age, respiratory distress and medical intervention; and (3) knowledge of tubular function and its maturation and the processes of postnatal adaptation. This knowledge and appropriate monitoring are the mainstay of management of neonatal fluid balance.


Protein dynamics and lipid affinity of monomeric, zeaxanthin-binding LHCII in thylakoid membranes.
The xanthophyll cycle in the antenna of photosynthetic organisms under light stress is one of the most well-known processes in photosynthesis, but its role is not well understood. In the xanthophyll cycle, violaxanthin (Vio) is reversibly transformed to zeaxanthin (Zea) that occupies Vio binding sites of light-harvesting antenna proteins. Higher monomer/trimer ratios of the most abundant light-harvesting protein, the light-harvesting complex II (LHCII), usually occur in Zea accumulating membranes and have been observed in plants after prolonged illumination and during high-light acclimation. We present a combined NMR and coarse-grained simulation study on monomeric LHCII from the npq2 mutant that constitutively binds Zea in the Vio binding pocket. LHCII was isolated from 13C-enriched npq2 Chlamydomonas reinhardtii (Cr) cells and reconstituted in thylakoid lipid membranes. NMR results reveal selective changes in the fold and dynamics of npq2 LHCII compared with the trimeric, wild-type and show that npq2 LHCII contains multiple mono- or digalactosyl diacylglycerol lipids (MGDG and DGDG) that are strongly protein bound. Coarse-grained simulations on npq2 LHCII embedded in a thylakoid lipid membrane agree with these observations. The simulations show that LHCII monomers have more extensive lipid contacts than LHCII trimers and that protein-lipid contacts are influenced by Zea. We propose that both monomerization and Zea binding could have a functional role in modulating membrane fluidity and influence the aggregation and conformational dynamics of LHCII with a likely impact on photoprotection ability.


Regulation and compartmentalization of androgens in rat prostate and muscle.
Male rats were castrated and treated with various doses of testosterone (T) or 5 alpha-dihydrotestosterone (DHT) by implantation of steroid releasing polydimethylsiloxane depots. After 14 days, the animals were killed and the concentration of T, DHT and 5 alpha-androstane-3 alpha,17 beta-diol (Diol) was measured by radioimmunoassay in plasma, in the homogenates of the prostate (PR), the bulbocavernosus/levator ani muscle (BCLA), skeletal muscle (SM) and heart muscle (HM), as well as in the cytosol and the nuclear fraction of these tissues. Additionally, the weight and DNA content of PR and the levator ani muscle were measured. The main results were: After T or DHT administration the main androgens in plasma were T or Diol, respectively, the concentration of each being linearly dependent from the administered steroid dose (T after T-: r = 0.97, P less than 0.001. Diol after DHT administration: r = 0.97, P less than 0.001). T in a dose of 60 micrograms/24 h maintained the concentrations of T, DHT and Diol in plasma in the range of untreated controls. Irrespective of the T doses administered, its concentration in PR tissue was comparatively low. T administration resulted in a significant accumulation of DHT in PR, when compared to plasma T. The steepest increase of DHT in PR was found with low doses of T administered (0.6-12 micrograms/24 h). At higher doses (12-600 micrograms/24 h) the further increase in the tissue was rather parallel to that of plasma T. A comparable picture was found for the DHT concentration in cytosol and in nuclei. The Diol concentration in the cytosol was linearly related to the administered T dose (r = 0.80, P less than 0.001). This steroid could not be detected in nuclei (less than 0.5 pmol/mg DNA). Administration of DHT in principle mimicked the DHT data observed after T treatment. In muscle homogenates no accumulation of neither T, DHT nor Diol was observed. In the nuclear fractions only after the highest doses of T measurable amounts of T and DHT were found. Whereas a positive correlation between DHT values in nuclei and weight increases in prostate was present, no such parallelism could be demonstrated in muscular tissue. The data are discussed with respect to the present knowledge of androgen binding and metabolism in different organs and to a possible specific role of nuclear DHT accumulation in mediating androgen dependent processes.


Rapid cognitive decline, one-year institutional admission and one-year mortality: analysis of the ability to predict and inter-tool agreement of four validated clinical frailty indexes in the SAFEs cohort.
To evaluate the predictive ability of four clinical frailty indexes as regards one-year rapid cognitive decline (RCD - defined as the loss of at least 3 points on the MMSE score), and one-year institutional admission (IA) and mortality respectively; and to measure their agreement for identifying groups at risk of these severe outcomes. One-year follow-up and multicentre study of old patients participating in the SAFEs cohort study. Nine university hospitals in France. 1,306 patients aged 75 or older (mean age 85±6 years; 65% female) hospitalized in medical divisions through an Emergency department. Four frailty indexes (Winograd; Rockwood; Donini; and Schoevaerdts) reflecting the multidimensionality of the frailty concept, using an ordinal scoring system able to discriminate different grades of frailty, and constructed based on the accumulation of identified deficits after comprehensive geriatric assessment conducted during the first week of hospital stay, were used to categorize participants into three different grades of frailty: G1 - not frail; G2 - moderately frail; and G3 - severely frail. Comparisons between groups were performed using Fisher's exact test. Agreement between indexes was evaluated using Cohen's Kappa coefficient. All patients were classified as frail by at least one of the four indexes. The Winograd and Rockwood indexes mainly classified subjects as G2 (85% and 96%), and the Donini and Schoevaerdts indexes mainly as G3 (71% and 67%). Among the SAFEs cohort population, 250, 1047 and 1,306 subjects were eligible for analyses of predictability for RCD, 1-year IA and 1-year mortality respectively. At 1 year, 84 subjects (34%) experienced RCD, 377 (36%) were admitted into an institutional setting, and 445 (34%) had died. With the Rockwood index, all subjects who experienced RCD were classified in G2; and in G2 and G3 when the Donini and Schoevaerdts indexes were used. No significant difference was found between frailty grade and RCD, whereas frailty grade was significantly associated with an increased risk of IA and death, whatever the frailty index considered. Agreement between the different indexes of frailty was poor with Kappa coefficients ranging from -0.02 to 0.15. These findings confirm the poor clinimetric properties of these current indexes to measure frailty, underlining the fact that further work is needed to develop a better and more widely-accepted definition of frailty and therefore a better understanding of its pathophysiology.


Impact of Selenium Nanoparticle-Enriched Lactobacilli Feeding Against Escherichia coli O157:H7 Infection of BALB/c Mice.
The effectiveness of selenium nanoparticle (SeNP)-enriched Lactiplantibacillus plantarum and Lactobacillus acidophilus was studied against Shiga toxin-producing Escherichia coli O157:H7 infection on the intestinal fragments and kidney tissue of BALB/c mice. Gut microbiota-targeted bacteria and E. coli O157:H7 counts were obtained by qPCR and PCR. Histology of ileum, colon, and kidney tissues and Stx secretions were analyzed until one-week post-infection. Mice fed with SeNP Lpb. plantarum in the preinfection feeding groups have lower E. coli O157:H7 counts and lower intestinal damage than those in the infected group. The lowest mean fecal probiotic counts were in the L. acidophilus group (7.61 log 10). In pretreatment groups of SeNP L. acidophilus and L. acidophilus, the mean counts of bacteria decreased to 104 CFU/g by day 7. The lowest Stx copy number was demonstrated in SeNP Lpb. plantarum feeding groups' day 7 (P < 0.05). Feeding groups with SeNP Lpb. plantarum had significantly higher members of Lactobacilli in their fecal microbiota than the control group on day 7. It was clarified that Se-enriched Lpb. plantarum and L. acidophilus can be useful as a method of preventing STEC infections. The viability of STEC infection exposure to selenium-enriched Lactobacillus spp. was decreased more than for non-Se-enriched Lactobacillus spp.


Analysis of RNase-A-resistant regions of adenovirus 2 major late precursor-mRNA in splicing extracts reveals an ordered interaction of nuclear components with the substrate RNA.
An RNase A protection assay was employed to investigate the interaction of nuclear components with a precursor-mRNA derived from the adenovirus 2 major late transcription unit in a splicing extract from HeLa cells. Upon incubation in the extract, two regions in the precursor-RNA become resistant to digestion with RNase A. After short incubation times (5 min) at 30 degrees C, fragments mapping upstream from the branch point in the intron are obtained. After ten minutes or more, additional oligonucleotides, derived from the 5' splice site, are protected. RNase A protection of different RNA substrates demonstrates that a 5' splice site is not required for the binding of components to the branch point region. For interaction with this site, the polypyrimidine stretch just upstream from the 3' splice site is essential. Binding to the 5' splice site occurs only in the presence of an intact 3' end of the intron. Preincubation of the extract with excess unlabelled RNA containing only a 3' splice site leads to efficient competition of binding, both in the branch point region and at the 5' splice site, whereas an RNA that contains only 5'-splice-site sequences has no effect on the interaction with the mRNA precursor. This indicates that stable association with the 5' splice site requires prior binding of components in the branch point region. When splicing complexes are digested with RNase A, it becomes apparent that only the branch point region is sequestered into a ribonucleoprotein (RNP) structure in the 35 S complex. The 5' splice site becomes resistant to RNase A only when a 50 S splicing complex has been assembled. Degradation of specific regions in U1, U2 and U4 RNA with complementary oligodeoxynucleotides and RNase H has been used to analyse involvement of the U small nuclear RNPs (snRNPs) in the protection reaction. The 5' end of U2 RNA is essential for protection of the branch point region. RNA sequences in a loop of U2 RNA (nucleotides 65 to 78) are required for the formation of an RNase-A-resistant structure at the 5' splice site. Taken together, these results suggest that U2 snRNP participates in the formation of a pre-splicing complex, the 5' end of its RNA being involved in the observed binding. Conversion to a 50 S splicing complex is obtained after the binding of U1 and U4/U6 snRNPs, which also requires sequences in a loop of U2 RNA. Possible interactions between the individual snRNPs and between snRNPs and precursor-mRNA are discussed.


Biogas production from plant biomass used for phytoremediation of industrial wastes.
In present study, potentials of water hyacinth (Eichhornia crassipes) and water chestnut (Trapa bispinnosa) employed for phytoremediation of toxic metal rich brass and electroplating industry effluent, were examined in terms of biogas generation. Inability of the plants to grow in undiluted effluent directed to select 20%, 40% and 60% effluent concentrations (with deionized water) for phytoremediation experiments. Slurry of both the plants used for phytoremediation produced significantly more biogas than that by the control plants grown in unpolluted water; the effect being more pronounced with plants used for phytoremediation of 20% effluent. Maximum cumulative production of biogas (2430c.c./100gdm of water hyacinth and 1940c.c./100gdm of water chest nut) and per cent methane content (63.82% for water hyacinth and 57.04% for water chestnut) was observed at 5mm particle size and 1:1 substrate/inoculum ratio, after twenty days incubation. Biogas production was quicker (maximum from 8-12days) in water hyacinth than in water chestnut (maximum from 12-16days). The qualitative and quantitative variations in biogas production were correlated with COD, C, N, C/N ratio and toxic metal contents of the slurry used.


A DICOM Based Collaborative Platform for Real-Time Medical Teleconsultation on Medical Images.
The paper deals with the design of a Web-based platform for real-time medical teleconsultation on medical images. The proposed platform combines the principles of heterogeneous Workflow Management Systems (WfMSs), the peer-to-peer networking architecture and the SPA (Single-Page Application) concept, to facilitate medical collaboration among healthcare professionals geographically distributed. The presented work leverages state-of-the-art features of the web to support peer-to-peer communication using the WebRTC (Web Real Time Communication) protocol and client-side data processing for creating an integrated collaboration environment. The paper discusses the technical details of implementation and presents the operation of the platform in practice along with some initial results.


Influence of metiamide and atropine on pepsinogen secretion in the conscious rat.
Activity of peptic cells is influenced directly by cholinolytic or cholinergic agents. Histamine H2-antagonists influence the activity of the chief cells through changes of acidity of gastric juice.


A comparison of the speech results after early and delayed hard palate closure; a preliminary report.
An "early surgery" and a "delayed surgery" group of cleft palate cases' speech has been recorded and judged in two ways. Initially four different listener groups gave their "impressions" of the speech samples followed by the two speech therapist groups assessing specific aspects of speech. For analytical purposes the delayed surgery group was divided into "repaired" and "unrepaired" hard palate groups. The general conclusion was that delaying hard palate surgery may be responsible for the persistence of noticeable abnormal speech patterns until after hard palate repair. However, despite their higher frequency in the "delayed unrepaired" group, errors of tongue placement and airstream direction were common to all groups. The relative influence of maturation, surgery and speech therapy on speech progress has not been considered. It is suggested that a final review of oro-facial growth and speech as each subject reaches 17 years old would give more definitive results. Then the subjects might discuss the relative importance of facial appearance and speech results.


[Erythropoietin before severe hypospadias repair: fewer complications?].
To study the effect of a preparation by erythropoietin before Onlay's intervention on postoperative hematocrits and medium-term results of the surgery. Twenty-one patients were operated on by Onlay's technique between 2001 January and 2008 September, after being treated by erythropoietin. Seven had a midshaft hypospadias, two a posterior hypospadias and 12 a penoscrotal hypospadias. All children were examinated four months after surgery to evaluate the surgical results. After the surgery, 18 children had an apical meatus (85.7%). Three had a balanopreputial meatus, two a stenosis of the meatus. Two children were reoperated on, one with the Duplay's technique, the other for a meatostomy. No fistula, no necrosis of the preputial flap was observed. The preoperative hematocrit was measured at 41%, with an increase of 3.8% because of the preparation. Peroperative blood loss was evaluated at 6.6%. After surgery, 12 children had an hematocrit inferior than 35%, four an hematocrit inferior than 30%. No transfusion was needed. Preparation by erythropoietin before severe hypospadias surgery seemed to have several advantages: a more elevated hematocrit after surgery than with an iron preparation alone, and a lower rate of postoperative complications, including fistulas and necrosis of the preputial flap.


Effect of the cannabinoid receptor ligand, WIN 55,212-2, on superoxide anion and TNF-alpha production by human mononuclear cells.
Cannabinoids are known to downregulate immune response but the role for cannabinoid receptors in cannabinoid-induced immunosuppression is still unclear. To address this question, the interference of CB1 and CB2 receptor antagonists with the inhibition of TNF-alpha production by synthetic cannabinoid WIN 55,212-2 was studied using human peripheral blood mononuclear cells (PBMC) in vitro. CB2 (SR 144528) but not CB1 (SR 141716A) receptor antagonist dose dependently interfered with WIN 55,212-2-induced inhibition of TNF-alpha synthesis. Also, WIN 55,212-2 decreased fMLP-induced reactive oxygen species generation in lipopolysaccharide (LPS)-primed PBMC. However, the high concentrations of cannabinoid receptor ligands needed to achieve significant effects suggest that the observed effects may be in part cannabinoid receptor independent.


Gossypol uncoupling of respiratory chain and oxidative phosphorylation in ejaculated boar spermatozoa.
Gossypol, a promising male contraceptive isolated from cottonseed oil, inhibits spermatozoal motility. This antimotility effect accompanies a biphasic change in the spermatozoal respiratory rate: a stimulation at low concentrations and an inhibition at high concentrations. With various respiratory inhibitors, gossypol was shown to take effect by the uncoupling of the respiratory chain and the oxidative phosphorylation. The implication of this uncoupling action in the strategy of producing an ideal gossypol-like male contraceptive is discussed.


Specific language impairment.
The acquisition of language is one of the most important achievements in young children, in part because most children appear to acquire language with little effort. Some children are not so fortunate, however. There is a large group of children who also have difficulty learning language, but do not have obvious neurological, cognitive, sensory, emotional, or environmental deficits. Clinicians often refer to these children as language disordered or language impaired. Researchers tend to refer to these children as specific language impaired (SLI). Children with SLI have intrigued researchers for many years because there is no obvious reason for their language learning difficulties. SLI has been found to be an enduring condition that begins in early childhood and often persists into adolescence and adulthood. The language problems of children with SLI are not limited to spoken language; they also affect reading and writing and thus much of academic learning. Knowledge of the characteristics of SLI should aid physicians, pediatricians, and early childhood specialists to identify these children during the preschool years and ensure that they receive appropriate services. With high-quality language intervention and literacy instruction, most children with SLI should be able to perform and function adequately in school and beyond.


[Two cases of massive pulmonary embolism associated with estrogen intake. Diagnostic and therapeutic usefulness of pulmonary angiography].
Two cases of massive pulmonary embolism observed in patients under estrogen therapy, are presented. We describe the clinical findings, highlighting the value of the arteriography in the diagnosis and the use of fibrinolytic therapy, being successful in both cases.


Strain-Guided Management of Potentially Cardiotoxic Cancer Therapy.
In patients at risk of cancer therapy-related cardiac dysfunction (CTRCD), initiation of cardioprotective therapy (CPT) is constrained by the low sensitivity of ejection fraction (EF) for minor changes in left ventricular (LV) function. Global longitudinal strain (GLS) is a robust and sensitive marker of LV dysfunction, but existing observational data have been insufficient to support a routine GLS-guided strategy for CPT. This study sought to identify whether GLS-guided CPT prevents reduction in LVEF and development of CTRCD in high-risk patients undergoing potentially cardiotoxic chemotherapy, compared with usual care. In this international, multicenter, prospective, randomized controlled trial, 331 anthracycline-treated patients with another heart failure risk factor were randomly allocated to CPT initiation guided by either ≥12% relative reduction in GLS (n = 166) or >10% absolute reduction of LVEF (n = 165). Patients were followed for EF and development of CTRCD (symptomatic EF reduction of >5% or >10% asymptomatic to <55%) over 1 year. Of 331 randomized patients, 2 died, and 22 withdrew consent or were lost to follow-up. Among 307 patients (age: 54 ± 12 years; 94% women; baseline LVEF: 59 ± 6%; GLS: -20.6 ± 2.4%) with a median (interquartile range) follow-up of 1.02 years (0.98 to 1.07 years), most (n = 278) had breast cancer. Heart failure risk factors were prevalent: 29% had hypertension, and 13% had diabetes mellitus. At the 1-year follow-up, although the primary outcome of change in LVEF was not significantly different between the 2 arms, there was significantly greater use of CPT, and fewer patients met CTRCD criteria in the GLS-guided than the EF-guided arm (5.8% vs. 13.7%; p = 0.02), and the 1-year EF was 57 ± 6% versus 55 ± 7% (p = 0.05). Patients who received CPT in the EF-guided arm had a larger reduction in LVEF at follow-up than in the GLS-guided arm (9.1 ± 10.9% vs. 2.9 ± 7.4%; p = 0.03). Although the change in LVEF was not different between the 2 arms as a whole, when patients who received CPT were compared, those in the GLS-guided arm had a significantly lower reduction in LVEF at 1 year follow-up. Furthermore, GLS-guided CPT significantly reduced a meaningful fall of LVEF to the abnormal range. The results support the use of GLS in surveillance for CTRCD. (Strain Surveillance of Chemotherapy for Improving Cardiovascular Outcomes [SUCCOUR]; ACTRN12614000341628).


Human regulatory T cells rapidly suppress T cell receptor-induced Ca(2+), NF-κB, and NFAT signaling in conventional T cells.
CD4(+)CD25(hi)Foxp3(+) regulatory T cells (T(regs)) are critical mediators of self-tolerance, which is crucial for the prevention of autoimmune disease, but T(regs) can also inhibit antitumor immunity. T(regs) inhibit the proliferation of CD4(+)CD25(-) conventional T cells (T(cons)), as well as the ability of these cells to produce effector cytokines; however, the molecular mechanism of suppression remains unclear. Here, we showed that human T(regs) rapidly suppressed the release of calcium ions (Ca(2+)) from intracellular stores in response to T cell receptor (TCR) activation in T(cons). The inhibition of Ca(2+) signaling resulted in decreased dephosphorylation, and thus decreased activation, of the transcription factor nuclear factor of activated T cells 1 (NFAT1) and reduced the activation of nuclear factor κB (NF-κB). In contrast, Ca(2+)-independent events in T(cons), such as TCR-proximal signaling and activation of the transcription factor activator protein 1 (AP-1), were not affected during coculture with T(regs). Despite suppressing intracellular Ca(2+) mobilization, coculture with T(regs) did not block the generation of inositol 1,4,5-trisphosphate in TCR-stimulated T(cons). The T(reg)-induced suppression of the activity of NFAT and NF-κB and of the expression of the gene encoding the cytokine interleukin-2 was reversed in T(cons) by increasing the concentration of intracellular Ca(2+). Our results elucidate a previously unrecognized and rapid mechanism of T(reg)-mediated suppression. This increased understanding of T(reg) function may be exploited to generate possible therapies for the treatment of autoimmune diseases and cancer.


Engineering the transcriptional activator NifA for the construction of Rhodobacter sphaeroides strains that produce hydrogen gas constitutively.
Purple non-sulfur photosynthetic bacteria such as Rhodobacter sphaeroides and Rhodopseudomonas palustris produce hydrogen gas (H2) via proton reduction, which is catalyzed by nitrogenase. Although the expression of nitrogenase is usually repressed under nitrogen-sufficient conditions, a partial deletion of nifA, which encodes a transcriptional activator of nitrogen-fixation genes, has been reported to enable the constitutive expression of nitrogenase in R. palustris. In this study, we evaluated the effects of a similar mutation (nifA* mutation) on H2 production during the photoheterotrophic growth of R. sphaeroides, based on the notion that H2 production by nitrogenase compensates for the loss of CO2 fixation via the Calvin cycle, thereby restoring the redox balance. The chromosomal nifA* mutation resulted in the slight restoration of the photoheterotrophic growth of a mutant strain lacking ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO), the key enzyme of the Calvin cycle, when the strain was cultured in van Niel's yeast medium. In addition, the strain with the nifA* mutation produced detectable levels of H2 during photoheterotrophic growth with acetate and ammonium; however, the H2 production was considerably lower than that observed during the photoheterotrophic growth of the strain with acetate and L-glutamate, where L-glutamate serves as a poor nitrogen source, thereby causing nitrogenase derepression. On the other hand, introduction of a multicopy plasmid harboring nifA* markedly restored the photoheterotrophic growth of the RubisCO-deletion mutant in van Niel's yeast medium and resulted in efficient H2 production during the photoheterotrophic growth with acetate and ammonium.


Drivers of hospitalization in atrial fibrillation: A contemporary review.
Atrial fibrillation (AF)-related hospitalization has risen over the last 2 decades and is the most influential determinant of total disease-related expenditure. In this review article, we describe several identified drivers of hospitalization from several registries and large-scale clinical trials, including key cardiovascular and non-traditional risk factors. We also discuss available assessment tools for discerning overall risk of hospitalization, including AF symptom scores, thrombosis and bleeding disposition, and non-invasive cardiac structural assessment. Finally, we highlight the different treatment paradigms that have been proven to reduce AF burden, progression, and hospitalization in the literature.


Pharmacokinetics and Safety of a Single Oral Dose of Peficitinib (ASP015K) in Japanese Subjects with Normal and Impaired Renal Function.
This study measured and compared the exposure and safety of peficitinib (ASP015K), a novel oral Janus kinase inhibitor, in subjects with normal and impaired renal function after a single oral, clinically relevant peficitinib dose. This was an open-label, parallel-group study conducted at two centres in Japan. Subjects with normal and mildly, moderately, or severely impaired renal function received a single oral dose of peficitinib (one 150 mg tablet) under fasting conditions in a hospital setting. Blood samples were collected prior to administration and up to 72 h post-dose for pharmacokinetic assessment. Safety was assessed up to 7 days post-dose. Peficitinib plasma concentration-time profiles were similar between those with normal and impaired renal function. In subjects with impaired renal function, area under the plasma concentration-time curve and maximum concentration were 0.8- to 1.1-fold those in subjects with no impairment. Two subjects (one in the normal group and one in the mildly impaired group) each experienced a treatment-emergent adverse event (TEAE). There were no serious TEAEs, deaths or TEAEs leading to treatment withdrawal. Peficitinib exposure and TEAEs were similar in subjects with and without renal impairment after a single oral 150 mg dose. Based on these findings, it is not expected that peficitinib dose adjustment will be required in clinical practice, according to the degree of renal impairment. CLINICALTRIALS. NCT02603497.


Dendritic cell maturation by innate lymphocytes: coordinated stimulation of innate and adaptive immunity.
Pathogen recognition by Toll-like receptors (TLRs) on dendritic cells (DCs) leads to DC maturation and the initiation of adaptive immunity. Recent studies have shown that innate lymphocytes--natural killer (NK), natural killer T (NKT), and gammadelta T cells--also trigger DC maturation. This interaction in turn expands and activates innate lymphocytes and initiates adaptive T cell immunity. Here, we comment on the evidence that these pathways are TLR independent and have the potential to respond to infection, malignancy, and immunotherapy.


Growing Kidney Tissue from Stem Cells: How Far from "Party Trick" to Medical Application?
The successful generation of kidney-like structures from human pluripotent stem cells, although slower to come than other tissue types, brings the hope of new therapies. While the demand for alternative treatments for kidney failure is acute, huge challenges remain to move these exciting but preliminary results toward clinical use.


Barriers and Facilitators to the Online Delivery of a School-Based Intervention to Reduce Racial Trauma.
Students of color face disproportionate rates of adverse childhood experiences, including racial discrimination in school settings. Effective interventions strategies are needed to address school-based racial trauma. Link for Equity was designed to be a culturally-responsive trauma-informed intervention that includes universal cultural humility training for teachers. As a result of the COVID-19 pandemic, the in-person trauma-informed cultural humility training was adapted for online delivery. The purpose of this study was to assess barriers and facilitators that impacted online delivery of the training. We conducted semi-structured interviews with 25 high school teachers from three public school districts in the Midwestern United States who participated in the online training. Interview transcripts were coded by two team members, and thematic analysis was utilized. Barriers and facilitators to online delivery were identified across five domains: receptivity, logistics, engagement, comfort, and application. The implications of these barriers and facilitators are discussed and tailored recommendations for the virtual delivery of culturally-responsive trauma-informed interventions to reduce racial discrimination in schools are provided.


Actin from the nematode, Caenorhabditis elegans, is a single electrofocusing species.
We have prepared actin from wild type Caenorhabditis elegans animals by three procedures: a purification dependent on the ability of actin to form F-actin, affinity chromatography which preferentially binds G-actin, and co-precipitation of an actin-myosin complex by antimyosin antibodies. Each preparation yields a single electrofucsing species of actin. Comparison of actin from C. elegans embryos and animals reveals that embryos also have the same single electrofocusing species of actin.


ASTRO Journals' Data Sharing Policy and Recommended Best Practices.
Transparency, openness, and reproducibility are important characteristics in scientific publishing. Although many researchers embrace these characteristics, data sharing has yet to become common practice. Nevertheless, data sharing is becoming an increasingly important topic among societies, publishers, researchers, patient advocates, and funders, especially as it pertains to data from clinical trials. In response, ASTRO developed a data policy and guide to best practices for authors submitting to its journals. ASTRO's data sharing policy is that authors should indicate, in data availability statements, if the data are being shared and if so, how the data may be accessed.


Ultrahigh-Resolution Mass Spectrometry Method for Resolving 13C-Enrichment Patterns in a Microalgal Lipidome.
The analysis of 13C-labeled lipids by mass spectrometry is challenging due to the complexity from labeling the large number of carbon atoms in lipids. To further add to the complexity, different adducts can be produced during electrospray ionization and in-source fragmentation, which can create complex overlapping isotope patterns that can only be resolved using high-resolution mass spectrometry. Co-elution of lipids even after chromatographic separation also adds to the potential for overlapping mass spectra. Here, we describe a procedure that enables full 13C-labeled patterns to be resolved in complex microalgal lipid extracts as well a procedure that provides structural labeling information. Mass resolving powers of 240000 full width half-maximum (fwhm) and fast targeted MS/MS allowed the differentiation of isotopologues, adducts, and unresolved lipid species after chromatographic separation. This enabled the percentage of 13C enrichment to be calculated for each individual lipid species over a time series in the microalgal lipidome. The application of tandem mass spectrometry (MS/MS) also allowed the degree of labeling within the headgroup vs acyl chains to be determined, further adding to the detail of information collected. This information is particularly useful for studying lipid synthesis and remodeling processes and can be extended to other biological systems.


Kinetic investigations of the autoxidation of adrenalin.
Generation rates of superoxide anions (O2-) by autoxidizing adrenalin at pH 9.5 were determined in solutions containing either superoxide dismutase (0.85 M-1 S-1) or hydroxylamine (0.0185 M-1 S-1) as competitive scavengers. The rate constants of O2- with adrenalin and hydroxylamine were calculated for neutral and alkaline solutions. The respective values were for adrenalin: 5.6 X 10(4) M-1 S-1, pH 7.8; 7.0 X 10(3) M-1 S-1, pH 9.5--and for hydroxylamine 5.9 X 10(4) M-1 S-1, pH 7.8; 3.4 X 10(4) M-1 S-1, pH 9.5. The effects of various competitors and O2- sources on the rate constants were compared.


Another method for specifying furanose ring puckering.
A set of pseudorotation coordinates is proposed for characterizing the puckering of the furanose ring. These are defined from the curvilinear displacements of the C1' and C4' atoms from the planar conformation. The present coordinates have some practical advantages over the ones currently used.


Impact of endoscopic ultrasound-guided fine-needle aspiration in prospective liver transplant recipients with hepatocellular carcinoma and lymphadenopathy.
Diagnosis of metastatic disease is important in patients with cirrhosis and hepatocellular carcinoma (HCC) to prevent futile liver transplantation. Some of these patients have metastatic lymphadenopathy; however, it is difficult to perform percutaneous fine-needle aspiration due to presence of collateral and anatomic location. Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) of lymph nodes offers several advantages like real-time vision, proximity to target, and avoidance of collaterals. The aim of this study was to look for metastatic lymphadenopathy by EUS-guided FNA (EUS-FNA) in prospective liver transplant recipients with HCC. A prospective study was conducted from January 2013 to January 2016 at a tertiary care center. All prospective liver transplant recipients with HCC had PET-CT and bone scan to look for metastatic disease. EUS-FNA was done in patients with abdominal or mediastinal lymphadenopathy and no evidence of extrahepatic disease. Data is shown as median (25-75 interquartile range). EUS-guided FNA was done for 50 patients (42 abdominal and 8 mediastinal lymph nodes), age 57 (53-62) years, Child-Turcotte-Pugh 7 (6-9), and model for end-stage liver disease 10 (7-16). FNA material was adequate in 92% patients, metastasis in 15 (30%), granulomatous lymphadenopathy in 4 (8%), and reactive change in 27 patients (54%). The material was inadequate for diagnosis in 4 (8%) patients. Thus, EUS-guided FNA precluded transplantation in 30% of patients with lymphadenopathy, and 4 (8%) patients received anti-tubercular therapy before liver transplantation. In patients with HCC and lymphadenopathy, EUS-guided FNA detected metastatic disease and precluded liver transplantation in approximately one third of patients.


Fluoxymesterone stimulation of tumor marker secretion in patients with breast carcinoma.
The gross cystic disease fluid protein of 15,000 MW (GCDFP-15) has been demonstrated to be a circulating glycoprotein tumor marker for breast carcinoma in approximately 40% of patients with advanced disease. A recent retrospective analysis of plasma GCDFP-15 levels in patients with advanced breast cancer suggested that androgen therapy could cause significant increases in plasma levels in the absence of disease progression. In order to evaluate the frequency, time course, and intensity of the androgen effect on GCDFP-15 production, a prospective study was initiated. Twenty-nine patients with stage IV breast carcinoma were treated with fluoxymesterone (20 or 30 mg/d). Plasma levels of GCDFP-15 and carcinoembryonic antigen (CEA) were measured by radioimmunoassay before and at various times during therapy. By day 6 of therapy, plasma GCDFP-15 had increased significantly (p = 0.03) from a mean basal level of 58 +/- 12 ng/ml to 160 +/- 60 ng/ml. By contrast, the mean CEA levels in the same patients increased only from 36 +/- 14 ng/ml. The distribution of percent increases in plasma GCDFP-15 was not uniform, but patients with high (greater than 82 ng/ml) basal levels had marked (greater than or equal to 75%) increases in 6/6 (100%) cases, whereas patients with low (less than 30 ng/ml) basal levels had similar increases in only 2/15 (13%) cases. Urinary excretion of GCDFP-15 usually paralleled the increases in plasma levels of the glycoprotein during the first six days of therapy. A linear correlation between percent change in plasma and percent change in urinary GCDFP-15 was demonstrated. A permanent cell line of human breast carcinoma, T47-D, was stimulated to secrete GCDFP-15 in vitro by androgen, but not by estrogen. From these data, we conclude that androgens can specifically stimulate secretion of GCDFP-15 by breast carcinoma tissue in most patients with elevated plasma levels of GCDFP-15, and in some patients with normal levels. The stimulation occurs within days and is not associated with clinical signs of tumor growth.


Immunoassays for riboflavin and flavin mononucleotide using antibodies specific to d-ribitol and d-ribitol-5-phosphate.
Riboflavin (vitamin B2), a water-soluble vitamin, plays a key role in maintaining human health. Though, numerous methods have been reported for the determination of total riboflavin (TRF) content in foods and biological samples, very few methods are reported for quantifying riboflavin and its coenzymes [flavin mononucleotide (FMN); flavin adenine dinucleotide (FAD)] individually. Recently, we have demonstrated that antibodies specific to d-ribitol and d-ribitol-5-phosphate also recognize riboflavin and FMN, respectively, and not vice-versa. In this study, we have evaluated these two antibodies for the analysis of riboflavin and FMN by indirect competitive ELISA (icELISA) in selected foods and pharmaceuticals. Under the optimal assay conditions, 50% inhibition concentration (IC50) and limit of detection (LOD, IC10) were 3.41ng/mL and 0.02ng/mL for riboflavin, and 7.84ng/mL and 0.24ng/mL for FMN, respectively, with detectable concentration range between 0.1 and 100ng of analytes and <0.1% cross-reactivity with other water-soluble vitamins. The amounts of TRF in food samples, as analyzed by icELISA using ribitol antibody, were 90-95% of the reported values in the literature or label values. Quantification of individual flavins (riboflavin and FMN) from the same food samples showed variation in their values compared to TRF, and were in good agreement with values obtained from HPLC and AOAC methods. Further, spiking and recovery analysis of food samples and pharmaceuticals showed no significant matrix effects. The immunoassays were validated in terms of accuracy and precision using inter- and intra-assays. The immunoassays developed in this study are sensitive and appears feasible for screening a large number of samples in the quantification of riboflavin and FMN in various biological samples, pharmaceuticals and natural/processed foods.


Identification of tetrodotoxin and fish species in a dried dressed fish fillet implicated in food poisoning.
There were five victims of neurotoxic food poisoning from a dried dressed fish fillet in Changhua County, Taiwan, in February 2000. The toxicity of the dried dressed fish fillets was 243 mouse units per g according to a tetrodotoxin bioassay. The partially purified toxin was identified as tetrodotoxin and anhydrotetrodotoxin. The sequence of the 376-nucleotide region in the cytochrome b gene of the mitochondrial DNA exhibited the same genotype as that of the toxic puffer fish Lagocephalus lunaris. The same single restriction site for Hinfl was found in the polymerase chain reaction (PCR) products from the dried dressed fish fillet and the muscle of L. lunaris, yielding two DNA fragments of 170 and 206 bp. However, no restriction site for Hinfl was found in the PCR products from other toxic puffer fishes, including Takifugu niphobles, Takifugu oblongus, and Takifugu rubripes. Therefore, the species of the dried dressed fish fillet was identified as L. lunaris and its causative agent was identified as tetrodotoxin.


Germ cell-specific enhancer activity of a repeated element in a variable region of the mouse genome.
We recently described a complex genetic structure on mouse chromosome 8, a region of the murine genome in which genetic rearrangements frequently occur. A large repeated element specific to this chromosome was found to overlap with one of the cadherin genes (Cad11). An additional degree of complexity became apparent with the identification, in a subset of laboratory strains of mice, of a retrogene integrated into one of the repeated units. Designated Sycp1-ps2, it originated from the early meiotic gene encoding Synaptonemal Complex Protein 1. We now report that, among wild Mus species in which the retrogene is not present, this region of Chr 8 shows a high degree of variability. Sequence analysis showed that integration of Sycp1-ps2 created a 5' transcription initiator element. Transcription of the pseudogene in the testis was directly demonstrated. A germ cell-specific enhancer activity was localized within a 1117 bp region of the repeat, which was sufficient to direct the expression of reporter genes in transgenic mice to late meiotic and post-meiotic spermatogenic cells.


Co-linear, double-uranyl coordination by an expanded Schiff-base polypyrrole macrocycle.
Expansion of a Schiff-base polypyrrolic macrocycle allows the formation of a binuclear uranyl complex with co-linear uranyl ions and a very short oxo-oxo distance.


Altered neurochemical parameters in the brains of mice (Frings) susceptible to audiogenic seizures.
In this study, several biochemical aspects of serotonergic neurons were compared in mice susceptible to audiogenic seizures (Frings) and in mice not susceptible to audiogenic seizures (CF 1). Tryptophan hydroxylase (TPH) activity was significantly lower in brains of Frings mice compared to CF1 mice; however, brain levels of 5-HT were similar in both strains. The significantly lower TPH activity in Frings mice was due to the altered kinetic characteristics of TPH activity in this strain. TPH from Frings mice had a significantly lower apparent maximal velocity and a significantly higher affinity for the substrate, as indicated by a lower apparent Km for tryptophan. The uptake of tryptophan and accumulation of 5-HT (following pargyline) were similar in Frings and CF 1 mice. The levels of 5-HT in selected brain regions of Frings and CF 1 mice were also similar, but NE levels were higher in the cerebral cortex and DA levels were higher in the neostriatum of Frings mice. It is unclear at this point what role, if any, 5-HT plays in susceptibility to audiogenic seizures in brains of Frings mice.


Isolation and characterization of pectin from peel of Citrus tankan.
A pectin was extracted from the peel of Citrus tankan with a yield of 2.75%. The uronic acid content was 80.0%, and the degree of methoxylation was 63.2%. The pectin was composed of D-GalA, D-Gal, L-Ara and L-Rha in the molar ratio of 100:11.3:3.6:2.6. The molecular weight was estimated to be approximately 9.2 x 10(4). The pectin formed a gel by conventional procedures.


In pregnant women with suspected VTE and low/intermediate or unlikely pretest probability, D-dimer rules out VTE at 3 mo.
Bellesini M, Robert-Ebadi H, Combescure C, et al. D-dimer to rule out venous thromboembolism during pregnancy: a systematic review and meta-analysis. J Thromb Haemost. 2021;19:2454-67. 34161671.


Plasmapheresis, lymphocytapheresis, and immunosuppressive drug therapy in multiple sclerosis.
Multiple sclerosis may ultimately be effectively treated using appropriate immunosuppressive regimens. Both cytotoxic drugs and therapeutic apheresis may constitute important therapeutic options. A number of studies are currently underway which will hopefully clarify the exact role of these treatment modalities in patients at different stages of disease.


Methylenetetrahydrofolate reductase gene polymorphisms and lung cancer: a meta-analysis.
So far, case-control studies on the association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and lung cancer provide controversial or inconclusive results. To clarify the effect of MTHFR polymorphisms on the risk of lung cancer, a meta-analysis of all case-control observational studies was performed. The studies provided 5,111/6,415 cases/controls for C677T and 5,087/6,232 cases/controls for A1298C. The heterogeneity (P=0.0001, I(2)=76.6%) for C677T among the eight studies was extreme. Cluster analyses based on the frequencies of the C677T genotype of the control group in each study revealed that the studies could not cluster together according to their ethnicity. The random effects (RE) model showed that the 677T allele was not associated with the risk of lung cancer compared with the C allele [OR=1.12, 95% confidence interval (CI) (0.97-1.28), P=0.12]. The contrast of homozygotes, recessive model, dominant model produced the same pattern of results as the allele contrast. In regard to the A1298C polymorphism, there was no heterogeneity among the seven studies comparing the C versus the A allele (P=0.24, I(2)=24.4%), but no significant association was detected by the RE model or the fixed effects model [FE odds ratio (OR)=0.99 (0.93-1.05) and RE OR=1.00 (0.92-1.08)]. The effect of MTHFR polymorphisms (C677T, A1298C) on the risk of lung cancer was undetectable, even though analyzed on a relatively good number of subjects (totally 11,526 subjects) by meta-analysis (statistical power = 93.9%). Although MTHFR polymorphisms were associated with the risk of colorectal cancer, leukemia, and gastric cancer supported by other meta-analysis, our pooled data suggest no evidence for a major role of these two variants in carcinogenesis of lung cancer. The results implied that different tumors evolve by different pathological pathways and the roles of MTHFR in cancer is determined by its target genes.


Comorbidities in Chilean patients with psoriasis: a Global Healthcare Study on Psoriasis.
Psoriasis is a chronic inflammatory skin disease associated with several important medical comorbidities. There are scant data available on the comorbidities of patients with psoriasis in South America. To examine the comorbidity profile of adult patients with psoriasis in Chile and its association with severity of psoriasis. This was a multicentre, cross-sectional study involving 16 hospitals and clinics in Chile, which used a 48-item questionnaire to study clinician- and patient-reported outcomes and comorbidities. Inferential analyses were performed by psoriasis severity, using Fisher exact test, Student t-test and multivariable logistic regression. In total, 598 adult patients with psoriasis were included (51.1% male; mean age 49.2 ± 15.1 years); 48.5% mild and 51.4% moderate to severe; Psoriasis Area and Severity Index 11.6 ± 11.5; body surface area 14.7 ± 18.2%. Plaque psoriasis was the most common phenotype (90.2%), followed by guttate (13.4%). Psoriatic arthritis occurred in 27.3% of patients. Comorbidities were reported in 60.2% of all patients with psoriasis. Frequent concomitant diseases were obesity (25.3%), hypertension (24.3%), Type 2 diabetes mellitus (T2DM) (18.7%), dyslipidaemia (17.4%), metabolic syndrome (16.7%) and depression (14.4%). After adjustment, significant associations were found between moderate to severe psoriasis and obesity, T2DM and nonalcoholic fatty liver disease (NAFLD) compared with mild psoriasis. We report a large study of comorbidities, including depression, dyslipidaemia, T2DM and NAFLD, in people with psoriasis in Chile. The prevalence of comorbidities with psoriasis in Chile appears similar to that found in Western countries, and emphasizes the importance of assessing patients with psoriasis for risk factors for and presence of, comorbid disease in a multidisciplinary setting.


Ileal entrapment as a complication of fractured pelvis.
A case of entrapment of small bowel in a fracture of the pelvis is presented. It was found on laparotomy in the present case, but contrast enema or computerized tomography have been reported as diagnostic of this rare, life-threatening condition.


Exosomes derived from human CD34+ stem cells transfected with miR-26a prevent glucocorticoid-induced osteonecrosis of the femoral head by promoting angiogenesis and osteogenesis.
Damaged endothelial cells and downregulated osteogenic ability are two key pathogenic mechanisms of glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH). Recent studies suggested that transplantation of CD34+ stem cell-derived exosomes (CD34+-Exos) can treat ischemic diseases by promoting neovascularization and that miR-26a is an important positive regulator of osteogenesis. Moreover, the biological effect of exosomes is closely related to their cargo miRNAs. However, it is not clear whether increasing the abundance of miR-26a in CD34+-Exos will inhibit the progress of GC-induced ONFH. MiR-26a was overexpressed in CD34+-Exos (miR-26a-CD34+-Exos) to increase their osteogenic potential. The angiogenic potential of miR-26a-CD34+-Exos was then examined through evaluations of migration and tube-forming capacities in vitro. In addition, in order to observe the osteogenic effect of miR-26a-CD34+-Exos on bone marrow stromal cells (BMSCs), Alizarin red staining, alkaline phosphatase (ALP) activity assays, and qPCR were carried out. Finally, miR-26a-CD34+-Exos were injected into a GC-induced ONFH rat model to prevent the progress of GC-induced ONFH. The biological effects of miR-26a-CD34+-Exos on the ONFH model were evaluated by micro-CT, angiography, and histological staining. Our data showed that miR-26a-CD34+-Exos enhanced human umbilical vein endothelial cell migration and tube-forming capacities. Furthermore, miR-26a-CD34+-Exos strengthened the osteogenic differentiation of BMSCs under the influence of GCs in vitro. Finally, the miR-26a-CD34+-Exos increased the vessel density and trabecular bone integrity of the femoral head in the GC-induced ONFH rat model, which inhibited the progress of ONFH. MiR-26a-CD34+-Exos protect the femoral head from damage caused by GCs by strengthening angiogenesis and osteogenesis. The biological effect of miR-26a-CD34+-Exos make them suitable for application in the prevention of GC-induced ONFH.


Meniscal lesions in knee joints of broiler fowls.
Post-mortem examination of the knee joints of 28 broiler type fowls revealed abnormalities in one or both medial menisci. Certain abnormalities appeared to be associated with knee ligament disruption. These included torn or frayed menisci and those which were displaced, usually in a mesial direction. Histopathological studies revealed that each of these abnormalities was normally associated with degenerative meniscal lesions. Other meniscal abnormalities showed no association with knee ligament disruption. Such menisci can be regarded as being of aberrant shape and most commonly the medial meniscus was enlarged and "discoid". Discoid medial menisci frequently showed histological abnormalities. As in other species, it is suggested that discoid menisci are predisposed to injury probably because of their larger contact area.


Neuro-immune interactions: The spectacular forest.
In this special issue of Neuron, we present a series of opinions and reviews on neuro-immune interactions. Recent insights into how profoundly the nervous and immune systems affect each other, bolstered by trans-disciplinary collaboration, have revolutionized both neuroscience and immunology. Like a forest ecosystem, an organism thrives or withers depending on the balance of its components. Highlighted in this special issue is a small sampling of the ever-growing list of diseases influenced by dysfunctional neuro-immune crosstalk, ranging from multiple sclerosis and brain cancer to long COVID and Alzheimer's.