Resistance and tolerance of myocardium in ischemia: experimental results.
The resistance of the normal myocardium to ischemia can be determined by the metabolic and electric investigations, and particularly by the determination of the intra-myocardial potentials. The aspect of V.F. and the metabolic changes allow aetiologic deductions on the V.F. and are helpful for the treatment.


Improving Collaboration Between Public Health and Medicine: A Timely Survey of Clinician Public Health Knowledge, Training, and Engagement.
To assess the core knowledge of health indicators, federal health programs, and public health functions in practicing clinicians along with perceptions of their education and engagement with public health. A paper survey in booklet form was administered to attendees at 2 general medical conferences in May 2019. The survey was divided into 5 sections: knowledge of health systems and policy, knowledge of public health concepts and function, public health engagement, public health education, and demographics. One hundred two surveys were received from 402 attendees (response rate, 24.3%). Most were male (56%), older than 50 years (51%), and physicians (86%). Respondents had a fairly good knowledge of federal health programs (77%) and public health functions (84%), but less than half had a personal interaction with public health in the past 2 years (45%) or were aware of how to work with public health organizations in their community (46%). Only a few respondents rated their public health training as good or excellent during their primary degree (7%) or graduate medical education (15%), and most (75%) were interested in learning more about public health and health policy. Respondents had generally good foundational knowledge of federal health programs and public health functions, although some gaps were identified. Inclusion of health policy and public health topics in continuing medical education would be well received by clinicians. To improve collaboration between public health and medicine, public health should personally engage clinicians more and explain how they can work together to improve population health.


Self-healing hydrogel as an injectable implant: translation in brain diseases.
Tissue engineering biomaterials are aimed to mimic natural tissue and promote new tissue formation for the treatment of impaired or diseased tissues. Highly porous biomaterial scaffolds are often used to carry cells or drugs to regenerate tissue-like structures. Meanwhile, self-healing hydrogel as a category of smart soft hydrogel with the ability to automatically repair its own structure after damage has been developed for various applications through designs of dynamic crosslinking networks. Due to flexibility, biocompatibility, and ease of functionalization, self-healing hydrogel has great potential in regenerative medicine, especially in restoring the structure and function of impaired neural tissue. Recent researchers have developed self-healing hydrogel as drug/cell carriers or tissue support matrices for targeted injection via minimally invasive surgery, which has become a promising strategy in treating brain diseases. In this review, the development history of self-healing hydrogel for biomedical applications and the design strategies according to different crosslinking (gel formation) mechanisms are summarized. The current therapeutic progress of self-healing hydrogels for brain diseases is described as well, with an emphasis on the potential therapeutic applications validated by in vivo experiments. The most recent aspect as well as the design rationale of self-healing hydrogel for different brain diseases is also addressed.


The role of endothelial nitric oxide in the anti-restenotic effects of liraglutide in a mouse model of restenosis.
Previous animal studies have shown that glucagon-like peptide-1 receptor agonists (GLP-1RAs) suppress arterial restenosis, a major complication of angioplasty, presumably through their direct action on vascular smooth muscle cells. However, the contribution of vascular endothelial cells (VECs) to this process remains unknown. In addition, the potential interference caused by severe hyperglycemia and optimal treatment regimen remain to be determined. Nine-week-old male C57BL6 (wild-type) and diabetic db/db mice were randomly divided into vehicle or liraglutide treatment groups (Day 1), and subject to femoral artery wire injuries (Day 3). The injured arteries were collected on Day 29 for morphometric analysis. Human umbilical vein endothelial cells (HUVECs) were used for in vitro experiments. One-way ANOVA, followed by Tukey's test, was used for comparisons. In wild-type mice, liraglutide treatment (5.7, 17, or 107 nmol/kg/day) dose-dependently reduced the neointimal area (20, 50, and 65%) without inducing systemic effects, and caused an associated decrease in the percentage of vascular proliferating cells. However, these effects were completely abolished by the nitric oxide synthase (NOS) inhibitor N-omega-nitro-L-arginine methyl ester. Next, we investigated the optimal treatment regimen. Early treatment (Days 1-14) was as effective in reducing the neointimal area and vascular cell proliferation as full treatment (Days 1-29), whereas delayed treatment (Days 15-29) was ineffective. In HUVECs, liraglutide treatment dose-dependently stimulated NO production, which was dependent on GLP-1R, cAMP, cAMP-dependent protein kinase, AMP-activated protein kinase (AMPK), and NOS. Subsequently, we investigated the role of liver kinase B (LKB)-1 in this process. Liraglutide increased the phosphorylation of LKB-1, and siRNA-induced LKB-1 knockdown abolished liraglutide-stimulated NO production. In severe hyperglycemic db/db mice, liraglutide treatment also suppressed neointimal hyperplasia, which was accompanied by reductions in vascular cell proliferation and density. Furthermore, liraglutide treatment suppressed hyperglycemia-enhanced vascular inflammation 7 days after arterial injury. We demonstrate that endothelial cells are targets of liraglutide, and suppress restenosis via endothelial NO. Furthermore, the protective effects are maintained in severe hyperglycemia. Our findings provide an evidence base for a future clinical trial to determine whether treatment with GLP-1RAs represents potentially effective pharmacological therapy following angioplasty in patients with diabetes.


Reaction of S-nitrosoglutathione with sulfhydryl groups in protein.
The covalent modification of sulfhydryl groups by S-nitrosoglutathione has been examined using model compounds. S-Nitrosoglutathione and thiol compounds causing extremely fast transnitrosation reaction and subsequent production of mixed disulfide. Yeast alcohol dehydrogenase is rapidly inactivated by S-nitrosoglutathione. The reversibility and Ellman test demonstrate that the inactivation is the result of covalent modification of sulfhydryl groups in this enzyme.


Giant-cell containing neoplasms of the pancreas: an aspiration cytology study.
Giant-cell containing neoplasms of the pancreas are rare with few reports documenting their cytologic appearance. Giant-cell containing neoplasms of the pancreas have been divided into two subtypes corresponding to the osteoclastic giant-cell tumor of the pancreas and the pleomorphic giant-cell carcinoma of the pancreas. Despite the better prognosis reported in some series for osteoclastic giant-cell tumors, the most recent edition of the World Health Organization classification lumps the two entities into a single category designated as undifferentiated carcinoma with osteoclast-like giant cells. Smears obtained from osteoclastic giant-cell tumors show numerous giant-cells with clustered overlapping, bland appearing nuclei containing prominent nucleoli consistent with an osteoclast-type multinucleated giant-cell. These neoplasms contain a second population of mononuclear cells showing more marked nuclear atypia. Pleomorphic giant-cell carcinomas are characterized by anaplastic giant-cells displaying marked nuclear pleomorphism. The mononuclear component is also pleomorphic with markedly atypical epithelioid and spindle shaped cells. In three reported cases, a tumor contained a mixture of the two cell patterns. Thus, undifferentiated carcinoma with osteoclast-like giant cells and pleomorphic giant cell carcinoma may represent a morphologic spectrum with pure osteoclast-like giant-cell tumors at one end and pleomorphic giant-cell carcinoma at the other. Fine-needle aspiration specimens from pure osteoclast-like giant-cell tumors will contain a population of bland multinucleated osteoclastic-like giant-cells that differ markedly from the anaplastic giant-cells of pleomorphic giant-cell carcinoma. The difference in the appearance of the giant-cells aids in distinction of the two neoplasms. When in pure form, the two neoplasms may follow different clinical courses.


Effects of polyethylene and polylactic acid microplastics on plant growth and bacterial community in the soil.
Microplastics (MPs), especially biodegradable MPs (BMPs) have attracted increasing attention in recent years. However, the effects of MPs with different biodegradability on the soil-plant systems are not well explored. In this study, the effects of polyethylene MPs (PEMPs) and polylactic acid MPs (PLAMPs) on physio-biochemical performance and metabolomic profile of soybean (Glycine max), as well as the bacterial communities in soil were investigated. Our results showed that PEMPs had no noticeable toxicity on the plant growth, while 0.1% PLAMPs significantly decreased the root length by 27.53% when compared with the control. The peroxidase (POD) activity was reduced and catalase (CAT) activity was increased by MPs in plant leaves. The metabolomics study suggested that the significantly affected metabolic pathway is amino acid metabolism. Additionally, Shannon and Simpson indices of rhizosphere soil were changed only under 0.1% PLAMPs. The key bacteria involved in the dinitrogen fixation were also altered. This study provides a novel insight into the potential effects of MPs with different biodegradability on soil-plant systems and highlights that BMPs might have stronger negative effects for terrestrial ecosystem, which needs to be further explored in future research.


Implications of the NO/cGMP system for olfaction.
The rapid and transient generation of pulses of either cAMP or IP3 is considered the primary reaction in olfactory signal transduction. There is some recent evidence suggesting that another second messenger system, involving cGMP, may also play an important role in olfactory signalling. High doses of odorant elicit a delayed and sustained elevation of cGMP levels due to the operation of the nitric oxide (NO) synthase/guanylyl cyclase system. The interplay of NO and cGMP is supposed to trigger molecular mechanisms, including adaptation processes, which enable the olfactory neuroepithelium to cope with strong stimuli. Furthermore, a characteristic pattern of staining for NO synthase in the olfactory bulb suggests that the NO/cGMP system may also participate in neuronal processing of the sensory input.


The FTIR studies of gels and thin films of Al2O3-TiO2 and Al2O3-TiO2-SiO2 systems.
In this work, samples in form of bulk ones and thin films were obtained using the sol-gel method. The bulk samples were heated at different temperatures (500 °C, 850 °C and 1100 °C) corresponding to the annealing process of coatings, deposited on different substrates by dipping and pulling out samples from the proper sol with the stable speed. Thin films of both Al2O3-TiO2 and Al2O3-TiO2-SiO2 systems were deposited on carbon, steel and titanium substrates in two different ways: as single layers obtained from Al2O3 sol, TiO2 sol and Al2O3 sol or deposited as mixed coatings from Al2O3-TiO2 sol as well as Al2O3-TiO2-SiO2 one. All bulk samples were studied by the FTIR spectroscopy and the X-ray diffractometry while thin films were also investigated by the electron microscopy. In the IR spectra of Al2O3-TiO2 samples, as well as gels and coatings, bands due to the vibrations of AlO bonds of the octahedrally and tetrahedrally coordinated aluminum were observed. The IR spectra of samples of Al2O3-TiO2-SiO2 system differ from that of Al2O3-TiO2 ones in presence of bands assigned to the SiO bond vibrations and in positions of bands due to AlO bond vibrations. In all spectra of bulk samples and coatings, the positions of TiO bond vibrations were ascribed basing on the IR spectra of the pure anatase and rutile.


Dried lemon slices improve the bowel cleansing quality of polyethylene glycol for colonoscopy preparation: randomized controlled trial.
Adequate bowel preparation is related to the quality of colonoscopy. Dried lemon slices can increase gastrointestinal peristalsis, which has shown potential as an adjuvant of bowel preparation. We hypothesized that the combination of dried lemon slices and PEG could improve the efficacy of bowel preparation and be more acceptable to participants. To investigate the effectiveness of lemon slices combined with PEG for colonoscopy preparation. This study was a prospective, single-center, randomized, controlled trial of 521 patients randomly assigned to two groups. A total of 254 patients were given lemon slices based on conventional 4-L PEG treatment for the bowel, while 267 patients received only 4-L PEG treatment. Patients' basic information, procedure-related parameters, adverse effects, and subjective feelings were collected by questionnaires. Intestinal tract cleanliness was scored according to the Boston bowel preparation scale (BBPS) by experienced endoscopists. Data were analyzed by the two-sample t-test or the chi-square test. The BBPS scores were significantly higher in the PEG + lemon slice group (P < 0.05). The taste acceptability, satisfaction, and willingness to repeat bowel preparation were significantly higher in the PEG+ lemon slice group (P < 0.05). However, a larger proportion of patients from the PEG+ lemon slice group (30.7%) suffered from abdominal distension compared with the PEG group (20.6%), while the incidence of other adverse effects was comparable between the two groups. The addition of dried lemon slices to conventional PEG showed its superiority for bowel preparation.


Competitive ELISA for the measurement of tau protein in Alzheimer's disease.
Tau protein is a major component of paired helical filaments (PHFs) which constitute the characteristic neurofibrillary tangle lesions observed in Alzheimer's disease. Two tau mAbs have been produced which show distinct patterns of immunoreactivity with intact human tau and with tau incorporated in PHFs. The mAb 423 recognises PHFs but not human tau on immunoblots whereas mAb 7/51 reacts with human tau but its epitope is buried within the PHF and is only exposed after formic acid treatment. A competitive ELISA has been developed for both of these mAbs and these have been used to quantify the two distinct tau epitopes in PHFs. Samples containing antigen are incubated with horseradish peroxidase-conjugated mAb at 4 degrees C for 16 h and non-adsorbed antibody then measured by binding, at 37 degrees C for 1 h, to a fragment of tau coated on microtitre plates. Bound enzyme-labelled antibody is measured kinetically using a spectrophotometer capable of automatically mixing the samples throughout a 2-min incubation with substrate and chromogen. The interfacing of the plate reader with a computer permits competitive curves to be plotted automatically using Softmax. Curves are fitted using a 4-parameter logistic algorithm which allows one to determine the relative immunoreactivity for different samples. The application of these assays to monitoring biochemical fractions and quantifying distinct immunochemical presentations of tau protein with these two mAbs is described.


Standardization of a simple method for the estimation of haemoglobin A2.
An improved method for the estimation of haemoglobin A2, at the same time precise, simple and cheap, is proposed. Haemoglobin A is separated from haemoglobin A2 by electrophoresis on Cellogel in discontinuous buffer at alkaline pH. The strips of cellulose acetate containing the haemoglobin fractions are completely dissolved in 80% acetic acid. The percentage of haemoglobin A2 present in each sample is calculated from the values for the spectrophotometric absorbance at 396 nm. The average percentage of haemoglobin A2 (+/- standard deviation) determined by this method was 2.31 +/- 0.37 in 51 normal subjects, and 4.64 +/- 0.53 in 29 subjects with heterozygous beta-thalassaemia.


Melphalan-induced DNA cross-linking in human melanoma cells and phytohaemagglutinin-stimulated lymphocytes in relation to intracellular drug content and cellular levels of glutathione.
Melphalan-induced DNA cross-linking was compared in a human melanoma cell line (RPMI 8322) and in phytohaemagglutinin (PHA)-stimulated lymphocytes. In both cell types a delayed induction of DNA cross-links was observed, with maximum DNA cross-linking occurring 6-12 hours after drug exposure. Significantly higher peak levels of DNA cross-links were found in PHA-stimulated lymphocytes, total DNA cross-linking being 2.5 times and DNA interstrand cross-linking 2.2 times higher. The intracellular content of free melphalan was 1.3-fold higher in RPMI 8322 cells, thus the lower DNA cross-linking was not due to a lower drug concentration in these cells. RPMI 8322 cells had a 1.8-fold higher level of glutathione, possibly indicating a higher capacity of these cells to inactivate melphalan.


[Effects of lead exposure on expression of mGluR5 in mRNA and protein levels of the cultured hippocampal neurons].
To study the effects on the expression of mGluR5 mRNA and protein levels in primarily cultured hippocampal neurons after lead exposure. Primary embryonic rat hippocampal neuronal culture was prepared. On the 3(rd) day of incubation, lead chloride solution was added into medium to produce four different lead exposure levels: 0, 1 x 10(-8) mol/L, 1 x 10(-6) mol/L, 1 x 10(-4) mol/L Pb(2+). After 10 days of incubation, the neurons were collected to measure the alteration of mGluR5 mRNA expression by real-time fluorescent quantity PCR and the expression of mGluR5 in protein level by Western blot. The studies revealed that mGluR5 mRNA expression was down-regulated after lead exposure in a dose-dependent manner. The mGluR5 mRNA expression of the lower lead-exposed neurons (Pb(2+) 10(-8) mol/L), the medium lead-exposed neurons(Pb(2+) 10(-6) mol/L), the higher lead-exposed neurons(Pb(2+) 10(-4) mol/L) were 0.724, 0.421, 0.321 times less than that of the controls, respectively. The Western blot demonstrated that mGluR5 expression in protein level should be decreased after lead exposure. The expression of mGluR5 in mRNA and protein levels should be down-regulated after lead exposure at different lead levels in a dose-dependent manner.


Sample sizes for constructing confidence intervals and testing hypotheses.
Although estimation and confidence intervals have become popular alternatives to hypothesis testing and p-values, statisticians usually determine sample sizes for randomized clinical trials by controlling the power of a statistical test at an appropriate alternative, even those statisticians who recommend the use of confidence intervals for inference. There is merit in achieving consistency in the techniques for data analysis and sample size determination. To that end, this paper compares sample size determination with use of the length of the confidence interval with that obtained by control of power.


Effect of degree of substitution on the microphase separation and mechanical properties of cellooligosaccharide acetate-based elastomers.
Thermoplastic elastomers (TPEs) have long been used in a wide range of industries. However, most existing TPEs are petroleum-derived polymers. To realize environmentally benign alternatives to conventional TPEs, cellulose acetate is a promising TPE hard segment because of its sufficient mechanical properties, availability from renewable sources, and biodegradability in natural environments. Because the degree of substitution (DS) of cellulose acetate governs a range of physical properties, it is a useful parameter for designing novel cellulose acetate-based TPEs. In this study, we synthesized cellulose acetate-based ABA-type triblock copolymers (AcCelx-b-PDL-b-AcCelx) containing a celloologosaccharide acetate hard A segment (AcCelx, where x is the DS; x = 3.0, 2.6, and 2.3) and a poly(δ-decanolactone) (PDL) soft B segment. Small-angle X-ray scattering showed that decreasing the DS of AcCelx-b-PDL-b-AcCelx resulted in the formation of a more ordered microphase-separated structure. Owing to the microphase separation of the hard cellulosic and soft PDL segments, all the AcCelx-b-PDL-b-AcCelx samples exhibited elastomer-like properties. Moreover, the decrease in DS improved toughness and suppressed stress relaxation. Furthermore, preliminary biodegradation tests in an aqueous environment revealed that the decrease in DS endowed AcCelx-b-PDL-b-AcCelx with greater biodegradability potential. This work demonstrates the usefulness of cellulose acetate-based TPEs as next-generation sustainable materials.


Comparison of meat quality between eland (Taurotragus oryx) and cattle (Bos taurus) raised under similar conditions.
Physical, chemical and sensory characteristics of meat were compared between non-domestic eland (Taurotragus oryx) bulls (n=6) and domestic Fleckvieh (Bos taurus) bulls (n=6) which were finished under controlled conditions of feeding and management. Musculus longissimus lumborum from eland were darker and less yellow in colour, with a higher pH24 and lower contents of intramuscular fat and total collagen, compared to cattle. Contents (mg/100 g muscle tissue) and proportions (g/100 g of FA determined) of SFA and MUFA were higher (P<0.01) in cattle. Although the proportion of total PUFA were higher (P<0.001) in eland, contents of PUFA were similar between species. Meat from cattle was consistently scored higher (P<0.05) for sensory texture characteristics, juiciness, flavour, and overall acceptance. We concluded that bulls of eland provided low-fat meat with a beneficial fatty acid composition from a human nutrition perspective, but with lower sensory scores, compared to bull beef.


Utility of the wavelet transform to analyze the stationarity of single ionic channel recordings.
Wavelet transform, a time-scale analysis, is presented as a new tool to analyze single-channel recordings. This method makes it possible to verify the stationarity, to identify episodes of change in the kinetic channel behavior (burst, flickering, cooperativity) or episodes of noise, and to localize stationary segments in long single-channel current recordings. It can help the conventional analysis of the kinetic behavior of ionic channels leading to better understand the gating mechanism.


Structural and Mechanical Properties of Doped Tobermorite.
As calcium silicate hydrate (C-S-H) is the main binding phase in concrete, understanding the doping behavior of impurity elements in it is important for optimizing the structure of cementitious materials. However, most of the current studies focus on cement clinker, and the doping mechanism of impurity elements in hydrated calcium silicate is not yet fully understood. The hydrated calcium silicate component is complex, and its structure is very similar to that of the tobermorite mineral family. In this study, the effects of three different dopants (Mg, Sr and Ba) on a representing structure of C-S-H-tobermorite-was systematically explored using densify functional theory (DFT) calculations. The calculations show that Mg doping leads to a decrease in lattice volume and causes obvious structure and coordination changes of magnesium-oxygen polyhedra. This may be the reason why high formation energy is required for the Mg-doped tobermorite. Meanwhile, doping only increases the volume of the Sr- and Ba-centered oxygen polyhedra. Specifically, the Mg-doped structure exhibits higher chemical stability and shorter interatomic bonding. In addition, although Mg doping distorts the structure, the stronger chemical bonding between Mg-O atoms also improves the compressive (~1.99% on average) and shear resistance (~2.74% on average) of tobermorillonite according to the elastic modulus and has less effect on the anisotropy of the Young's modulus. Our results suggest that Mg doping is a promising strategy for the optimized structural design of C-S-H.


Comparative study on hydrolases in five species of Ochromonas (chrysomonadina).
Acid phosphatase and beta-glucosidase were shown to be present in five species of Ochromonas grown in organic media (O. danica, O. malhanesis, O. munuta, O. sociabilis and Ochromonas sp. 933/4). Acid phosphatase was found to have a pH optimum at 4.0 in O. danica, and at 5.1 in the four other species. No alkaline phosphatase was found in any of the above mentioned species. Beta-glucosidase in the species studied has a pH optimum at 4.6. Low alpha-glucosidase activity was found only in O. danica. Acid phosphatase in all the five species shows an increase in activity during the logarithmic phase of growth and a decrease during the early stationary phase. Beta-glucosidase shows a similar behavior only in O. danica.


Comprehensive Analysis of Long-term Splenic Volume Changes in Pediatric Liver Transplant Patients: Does It Correlate With Adverse Graft Outcomes?
Splenomegaly and hypersplenism caused by liver failure increase the mortality and morbidity of patients even after liver transplantation if they do not regress. We evaluated the relation of splenic volume change and transplanted liver function. A total of 59 of 207 pediatric patients who had liver transplantation between 2013 and 2018 in our institute were evaluated. The relation of spleen volume changes (splenic volume to standard splenic volume ratio [SV/SSV]) were measured at 0, 1, 6, 12, 24, and 36 months of follow-up by constructing electronic three-dimensional structure of the spleen at dynamic computed tomography (CT), and the course of liver functions were evaluated. The SV/SSV ratio decreases in the first postoperative 6 months. After 6 months, SV increases and SV/SSV increases gradually. In a normal functioning graft, SV/SSV significantly decreased in all time points (P < .001). In patients with adverse events, SV/SSV started to increase after 6 months. In patients with fulminant hepatic failure, SV/SSV started to increase after postoperative 6 months. Adverse events in patients with fulminant hepatic failure were more than the patients with chronic liver disease (58% vs 28%). There was an inverse correlation between SV/SSV and thrombocyte levels (P < .001). SV/SSV seems to be correlated to the adverse events (ie, rejection). Together with thrombocyte levels, it can be used as a noninvasive test for follow-up of transplant patients in terms of adverse events in graft function.


Male factor infertility and placental pathology in singleton live births conceived with in vitro fertilization.
We sought to determine whether pregnancies conceived in those with male factor infertility have unique placental pathology profiles compared to those undergoing infertility treatments for other indications. This was a retrospective cohort study of placental pathology from 464 live births conceived from autologous fresh IVF cycles at an academic fertility center from 2004 to 2017. Placental pathology was compared between live births arising from patients with male factor infertility alone and those with another infertility diagnosis. Placental outcomes were compared with parametric or non-parametric tests; logistic regression was performed to account for potential confounders. Compared to cycles performed for a non-male factor diagnosis, male factor infertility cycles had a higher mean paternal age (38.2 years vs. 36.5 years, p < 0.001), a higher female mean BMI (24.3 vs. 23.3 kg/m2, p = 0.01), and a lower day 3 follicle stimulating hormone (FSH) level (6.8 vs. 7.3 IU/mL, p = 0.02). The mean numbers of embryos transferred, and day of transfer were similar between groups, and more cycles used ICSI in the male factor infertility group (90.6% vs. 22.5%, p < 0.001). Placental pathology in our adjusted model was similar between the male factor and non-male factor groups. In our unadjusted subgroup analysis, cycles for male factor using ICSI appeared to lead to more small placentas by weight compared to cycles performed with conventional insemination (45.8% < 10th percentile vs. 18.8%, p = 0.04). Male factor infertility is not associated with significantly different placental pathology compared to other infertility diagnoses.


Mutational spectrum in a Chinese cohort with congenital cataracts.
To identify the mutational spectrum in a Chinese cohort with congenital cataracts. Probands (n = 164) with congenital cataracts and their affected or unaffected available family members were recruited for clinical examinations and panel-based next-generation sequencing, then classified into a cohort for further mutational analysis. After recruitment (n = 442; 228 males and 214 females), 49.32% (218/442) of subjects received a clinical diagnosis of congenital cataracts, and 56.88% (124/218) of patients received a molecular diagnosis. Eighty-four distinct variants distributed among 43 different genes, including 42 previously reported variants and 42 novel variants, were detected, and 49 gene variants were causally associated with patient phenotypes; 27.37% of variants (23/84) were commonly detected in PAX6, GJA8 and CRYGD, and the three genes covered 33.06% of cases (41/124) with molecular diagnosis. The majority of genes were classified as genes involved in nonsyndromic congenital cataracts (19/43, 44.19%) and were responsible for 56.45% of cases (70/124). The majority of functional and nucleotide changes were missense variants (53/84, 63.10%) and substitution variants (74/84, 88.10%), respectively. Nine de novo variants were identified. This study provides a reference for individualized genetic counseling and further extends the mutational spectrum of congenital cataracts.


Continuous-infusion vancomycin therapy for preterm neonates with suspected or documented Gram-positive infections: a new dosage schedule.
Intermittent infusion of vancomycin is widely used to treat late-onset sepsis in neonates. On the other hand, the continuous infusion of vancomycin could improve bactericidal efficacy since its action is time dependent. To evaluate a simplified dosage schedule for continuous-infusion vancomycin therapy. Prospective study in premature neonates (<34 weeks) with suspected coagulase-negative staphylococci (CoNS) sepsis. Before antibiotics at time zero (T0), serum creatinine was measured and blood cultures were collected. Vancomycin dosage began with 25 mg/kg/day or 15 mg/kg/day (period 1) and 30 mg/kg/day or 20 mg/kg/day (period 2) depending on whether serum creatinine was below or above 90 mumol/l. Two days after beginning treatment (first timepoint: T1), serum vancomycin was measured and second blood cultures were collected. Between June 2002 and December 2005, 145 neonates were evaluated. At birth, the median (interquartile range) body weight was 920 (500-1160) g and gestational age was 28 (26-29) weeks. At T1, serum vancomycin was within the required range in 74.5% of neonates (108/145). Serum vancomycin levels were higher in period 2 than in period 1 (20 mg/l vs 13 mg/l, p<0.05). At T0, 55% (80/145) of blood cultures were positive for CoNS, but 71% (57/80) were negative at T1. Four days after beginning treatment, 92% of subjects had recovered without removing the central venous catheter. Using this simplified dosage schedule, bactericidal efficacy was maintained and most subjects had serum vancomycin concentrations within the therapeutic range.


Non-excisional laser therapies for hemorrhoidal disease: a systematic review of the literature.
Non-excisional laser therapies are emerging treatment for grades II and III hemorrhoidal disease (HD). However, so far, their efficiency is based on low-level evidence. Therefore, we aimed to systematically review the efficiency of non-excisional laser therapies for HD. MEDLINE/Pubmed, Web of science, Embase, and Cochrane were searched from database implementation until the April 17th, 2020. We included studies reporting at least one of surgical indicators of postoperative outcomes of laser therapies, encompassing laser hemorrhoidoplasty (LH) and hemorrhoidal laser procedure (HeLP). Fourteen studies describing LH and HeLP were included, representing 1570 patients. The main intraoperative complication was bleeding (0-1.9% of pooled patients for LH, 5.5-16.7% of pooled patients for HeLP). Postoperative complications occurred in up to 64% of patients after LH and 23.3% after HeLP. Resolution of symptoms ranged between 70 and 100% after LH and between 83.6 and 90% after HeLP. Moreover, four randomized controlled trials included in our review reported similar resolution after LH compared with hemorrhoidectomy or mucopexy and after HeLP compared with rubber band ligation. Recurrence rate was reported to range between 0 and 11.3% after LH and between 5 and 9.4% after HeLP. When compared with hemorrhoidectomy, LH showed conflicting results with one randomized controlled trial reporting similar recurrence rate, but another reporting decreased recurrences associated with hemorrhoidectomy. Laser therapies showed lower postoperative pain than hemorrhoidectomy or rubber band ligation. LH and HeLP are safe and effective techniques for the treatment of grades II and III HD.


Surgical Management of Barrett's-Related Neoplasia.
The management of Barrett's-related neoplasia has benefited from advances in endoscopic assessment, resection, and ablation, along with improved pathologic and radiographic staging. The development of specialized, high-volume esophageal multidisciplinary teams, with improvements in patient selection, preparation, perioperative care, minimally invasive operative approaches, and enhanced recovery after surgery programs, has contributed to improved outcomes for patients undergoing esophagectomy for Barrett's-related neoplasia.


Low-velocity simultaneous bilateral femoral neck fracture following long-term antiepileptic therapy: A case report.
Simultaneous bilateral femoral neck fractures are relatively rare injuries. They are usually associated with underlying metabolic bone disorders or systemic diseases. Long-term use of narcotics and bisphosphonates can also result in similar fracture patterns; however, association of this fracture type with long-term use of antiepileptic drugs is not very common. Only one such case has been reported in the literature. This article describes the second. We report a case of simultaneous displaced bilateral femoral neck fractures in a 50-year-old epileptic patient, who had taken phenytoin for the past 3 years. The fractures were a result of low-velocity injury following a fall from the bed. The fractures were managed with a bilateral hemi-replacement arthroplasty. Oral bisphosphonates were given to improve the bone quality in the post-operative period. The patient had a good post-operative outcome, that was sustained throughout the entire follow-up period of 1 year. Antiepileptic drugs should be supplemented with bisphosphonates and vitamin D to improve bone quality and prevent fractures in epileptic patients.


One-step simple sonochemical fabrication and photocatalytic properties of Cu2O-rGO composites.
An easy, one-step synthesis of Cu2O-reduced graphene composites (Cu2O-rGO) was developed using a simple sonochemical route without any surfactants or templates. The morphology and structure of the Cu2O-rGO composites were characterised using techniques such as scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, Raman spectroscopy and X-ray photoelectron spectroscopy (XPS). The results indicated that the Cu2O sphere is approximately 200 nm in diameter and composed of small Cu2O particles approximately 20 nm in diameter. The morphology and composition of the Cu2O-rGO composites could be well controlled by simply changing the mole ratio of the reactants under ultrasonic irradiation. The Cu2O-rGO composites displayed better photocatalytic performance for the degradation of methyl orange (MO) than pure Cu2O spheres, which may have potential applications in water treatment, sensors, and energy storage.


Maize transcription factor ZmBES1/BZR1-5 positively regulates kernel size.
The BES1/BZR1 transcription factors regulate the expression of genes responsive to brassinosteroids and play pivotal roles in plant development, but their role in regulating kernel development in maize remains unclear. In this study, we found that ZmBES1/BZR1-5 positively regulates kernel size. Association analysis of candidate genes in 513 diverse maize inbred lines indicated that three SNPs related to ZmBES1/BZR1-5 were significantly associated with kernel width and whilst four SNPs were related to 100-kernel weight. Overexpression of ZmBES1/BZR1-5 in Arabidopsis and rice both significantly increased seed size and weight, and smaller kernels were produced in maize Mu transposon insertion and EMS mutants. The ZmBES1/BZR1-5 protein locates in the nucleus, contains bHLH and BAM domains, and shows no transcriptional activity as a monomer but forms a homodimer through the BAM domain. ChIP-sequencing analysis, and yeast one-hybrid and dual-luciferase assays demonstrated that the protein binds to the promoters of AP2/EREBP genes (Zm00001d010676 and Zm00001d032077) and inhibits their transcription. cDNA library screening showed that ZmBES1/BZR1-5 interacts with casein kinase II subunit β4 (ZmCKIIβ4) and ferredoxin 2 (ZmFdx2) in vitro and in vivo, respectively. Taken together, our study suggests that ZmBES1/BZR1-5 positively regulates kernel size, and provides new insights into understanding the mechanisms of kernel development in maize.


Helicobacter pylori infection in immunized mice lacking major histocompatibility complex class I and class II functions.
The role of major histocompatibility complex (MHC) class I- and class II-restricted functions in Helicobacter pylori infection and immunity upon oral immunization was examined in vivo. Experimental challenge with H. pylori SS1 resulted in significantly greater (P </= 0.025) colonization of MHC class I and class II mutant mice than C57BL/6 wild-type mice. Oral immunization with H. pylori whole-cell lysates and cholera toxin adjuvant significantly reduced the magnitude of H. pylori infection in C57BL/6 wild-type (P = 0.0083) and MHC class I knockout mice (P = 0.0048), but it had no effect on the H. pylori infection level in MHC class II-deficient mice. Analysis of the anti-H. pylori antibody levels in serum showed a dominant serum immunoglobulin G1 (IgG1) response in immunized C57BL/6 wild-type and MHC class I mutant mice but no detectable serum IgG response in MHC class II knockout mice. Populations of T-cell-receptor (TCR) alphabeta+ CD4(+) CD54(+) cells localized to gastric tissue of immunized C57BL/6 wild-type and MHC class I knockout mice, but TCRalphabeta+ CD8(+) cells predominated in the gastric tissue of immunized MHC class II-deficient mice. These observations show that CD4(+) T cells engaged after mucosal immunization may be important for the generation of a protective anti-H. pylori immune response and that CD4(+) CD8(-) and CD4(-) CD8(+) T cells regulate the extent of H. pylori infection in vivo.


Effects of isoproterenol and forskolin on carbachol- and fluoroaluminate-induced polyphosphoinositide hydrolysis, inositol trisphosphate production, and contraction in bovine iris sphincter smooth muscle: interaction between cAMP and IP3 second messenger systems.
We have investigated the effects of isoproterenol (ISO) and forskolin on carbachol(CCh)- and fluoroaluminate (AlF4-)-induced phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis, myo-inositol 1,4,5-trisphosphate (IP3) production, 1,2-diacylglycerol, measured as phosphatidic acid (PA) formation, and contraction in the bovine iris sphincter smooth muscle. The data from these studies can be summarized as follows. (1) CCh (20 microM) stimulated significantly PIP2 hydrolysis, IP3 production, PA formation, and contraction. (2) Addition of ISO (0.1-25 microM), which raises the tissue cAMP level, to muscle precontracted with CCh attenuated PIP2 hydrolysis, IP3 production, PA formation and contraction in a time- and dose-dependent manner. (3) AlF4- (10 microM) induced a slow but progressive hydrolysis of PIP2, accompanied by parallel production of IP3, formation of PA, and contraction of the smooth muscle. The effects of AlF4- were dose-dependent and inhibited by deferoxamine, an Al3+ ion chelator. (4) Both forskolin (1-25 microM), which directly stimulates adenylate cyclase, and ISO inhibited the responses induced by AlF4- (10 microM) in a dose-dependent manner. (5) NaF (1-5 mM) had no effect on the activity of phospholipase C (PLC), purified from bovine iris sphincter. Furthermore, phosphorylation of the enzyme by catalytic subunit of protein kinase A had no inhibitory effect on PLC activity against PIP2. In conclusion, neither the muscarinic receptor nor PLC are the target sites for cAMP inhibition; instead the putative G-protein, which couples the activated muscarinic receptor to PLC, may be phosphorylated by cAMP-dependent protein kinase. This could attenuate the stimulation of PLC by the G-protein, thus resulting in inhibition of PIP2 hydrolysis and consequently leading to muscle relaxation. These results demonstrate cross-talk between the cAMP and IP3-Ca2+ second messenger systems and suggest that this could constitute a regulatory mechanism for the process of contraction-relaxation in smooth muscle.


Electroporation of subcutaneous mouse tumors by rectangular and trapezium high voltage pulses.
The artificial electrotransfer of bioactive agents such as drugs, peptides or therapeutical nucleic acids and oligonucleotides by membrane electroporation (MEP) into single cells and tissue cells requires knowledge of the optimum ranges of the voltage, pulse duration and frequency of the applied pulses. For clinical use, the classical electroporators appear to necessitate some tissue specific presetting of the pulse parameters at the high voltage generator, before the actual therapeutic pulsing is applied. The optimum pulse parameters may be derived from the kinetic normal mode analysis of the current relaxations due to a voltage step (rectangular pulse). Here, the novel method of trapezium test pulses is proposed to rapidly assess the current (I)/voltage (U) characteristics (IUC). The analysis yields practical values for the voltage U(app) between a given electrode distance and pulse duration t(E) of rectangular high voltage (HV) pulses, to be preset for an effective in vivo electroporation of mouse subcutaneous tumors, clamped between two planar plate electrodes of stainless steel. The IUC of the trapezium pulse compares well with the IUC of rectangular pulses of increasing amplitudes. The trapezium pulse phase (s) of constant voltage and 3 ms duration, following the rising ramp phase (r), yields a current relaxation which is similar to the current relaxation during a rectangular pulse of similar duration. The fit of the current relaxation of the trapezium phase (s) to an exponential function and the IUC can be used to estimate the maximum current at a given voltage. The IUC of the falling edge (phase f) of the trapezium pulse serves to estimate the minimum voltage for the exploration of the long-lived electroporation membrane states with consecutive low-voltage (LV) pulses of longer duration, to eventually enhance electrophoretic uptake of ionic substances, initiated by the preceding HV pulses.


Yellow Fever: A Perennial Threat.
Despite the availability of a safe and effective vaccine, yellow fever remains a major vaccine-preventable disease in endemic regions. Additionally, travelers risk acquiring yellow fever when visiting areas of endemic transmission or locations with ongoing outbreaks. Yellow fever is a viral hemorrhagic fever that has inflicted stigma, illness, and death among human societies. From the 17th to the 19th centuries, yellow fever remained a mysterious illness that predominantly affected tropical regions in Africa, the Caribbean and the Americas. The disease was as feared as cholera or smallpox, and played a significant geopolitical role in shaping modern societies. Epidemics of yellow fever brought out the best and the worst of human nature: the disease spread to new regions during the Atlantic slave trade; while the identification of its causative viral agent and mode of transmission, as well as the development of a vaccine, were made possible by the sacrifice of selfless scientists. Confirmation of the vector transmission of YF paved the way for the development of an effective vaccine in the first half of the 20th century. Encroachment of human settlements into locations with sylvatic transmission has blurred the distinction between the urban and sylvatic cycles. Introduction or expansion of routine immunization activities and reaching hard-to-reach populations consitute public health priorities toward ensuring vaccine equity in endemic areas. It is also critical to ensure the timely immunization of at-risk populations during outbreaks and to promote vaccination of international travelers. We conclude that the threat of YF will linger far into the 21st century as a leading public health emergency of global concern under the International Health Regulations.


Peer-Led Versus Conventional Teacher-Led Methodological Research Education Sessions: An Initiative to Improve Medical Education Research Teaching.
To enhance doctors' engagement with research, the National Medical Research Association (NMRA) developed a research teaching series, delivering peer-led (PL) sessions by medical students and conventional teacher-led (CL) sessions by licenced physicians/lecturers. We assessed the effectiveness of the series and compared the PL and CL approaches. The teaching sessions were delivered virtually via Zoom weekly either PL or CL. Feedback was provided by participants on completion of every session using a 10-point Likert scale assessing their knowledge pre- and post-training. A total of 87 participants were included generating 782 feedback forms, 367 (47.1%) for PL and 412 for CL sessions. The median knowledge scores significantly increased following each session (p-value < 0.05) independent of teaching approach. An overall improvement in the median knowledge score from all sessions from 5/10 to 8/10 was reported. There was no significant difference between knowledge gained from the CL or PL teaching. Didactic PL research training sessions are equally effective as CL sessions.


Close(d) to you? Avoidant attachment is associated with attenuated pupil responsivity to social stimuli.
Insecure attachment is thought to impair romantic relationships, presumably also contributing to mental health problems. Previous research has suggested a link to biased automatic processing of social information, potentially reflected in pupil dilation responses. To address this hypothesis, 37 adults were presented with attachment-related, emotional pictures of erotic couples, everyday couples, or interpersonal violence after assessment with the Experiences in Close Relationships Scale. Considerable variation in self-reported attachment behaviors regarding both attachment anxiety and avoidance was observed in our sample. Overall, pupil dilation was most pronounced during viewing of erotica and violence-related pictures. Relative to nature pictures as control, attachment avoidance was associated with attenuated pupillary responses to social content. However, this was not significant with erotica. For pictures of violence, this avoidant bias was also evident in reduced subjective arousal. In contrast, attachment anxiety was unrelated to differential pupil dilation. Our findings, although preliminary, suggest that previous attachment-related experiences may bias the processing of social stimuli, which in turn may be reflected in altered patterns of pupillary responses.


Explainable AI via learning to optimize.
Indecipherable black boxes are common in machine learning (ML), but applications increasingly require explainable artificial intelligence (XAI). The core of XAI is to establish transparent and interpretable data-driven algorithms. This work provides concrete tools for XAI in situations where prior knowledge must be encoded and untrustworthy inferences flagged. We use the "learn to optimize" (L2O) methodology wherein each inference solves a data-driven optimization problem. Our L2O models are straightforward to implement, directly encode prior knowledge, and yield theoretical guarantees (e.g. satisfaction of constraints). We also propose use of interpretable certificates to verify whether model inferences are trustworthy. Numerical examples are provided in the applications of dictionary-based signal recovery, CT imaging, and arbitrage trading of cryptoassets. Code and additional documentation can be found at https://xai-l2o.research.typal.academy .


A Further Validation of the Cognitive Bias Modification Effect on Trust in Middle Childhood.
Recent middle childhood research suggests that children's trust in maternal support can be manipulated using Cognitive Bias Modification (CBM) aimed at changing children's interpretation of ambiguous maternal support-related behavior. The current study with 60 children (40 girls, Mage = 10.62, SDage = 1.20) aimed to replicate previous research and to test whether the CBM effect is specific to trust or generalizes to other child evaluations of maternal behavior. More specifically, CBM effects on children's evaluation of parenting behavior were tested. Trust and maternal parenting behaviors were assessed using children's self-report. Results largely replicated previous findings, including the positive effect of CBM on children's trust in maternal support. Suggesting that this effect was specific for trust, the CBM manipulation did not affect children's appraisal of maternal parenting behavior. This finding supports the validity of CBM effects.


Reduced impact of emotion on choice behavior in presymptomatic BACHD rats, a transgenic rodent model for Huntington Disease.
Executive dysfunction and psychiatric symptoms are hallmarks of Huntington disease (HD), a neurodegenerative disorder genetically characterized by expanded CAG repeats in the HTT gene. Using the BACHD rat model of HD (97 CAG-CAA repeats), the present research seeks to characterize the progressive emergence of decision-making impairments in a rat version of the Iowa Gambling Task (RGT) and the impact of emotional modulation, whether positive or negative, on choice behavior. The choice efficiency shown both by WT rats (independent of their age) and the youngest BACHD rats (2 and 8months old) evidenced that they are able to integrate outcomes of past decisions to determine expected reward values for each option. However, 18months old BACHD rats made fewer choices during the RGT session and were less efficient in choosing advantageous options than younger animals. Presenting either chocolate pellets or electrical footshocks half-way through a second RGT session reduced exploratory activity (inefficient nose-poking) and choices with a weaker effect on BACHD animals than on WT. Choice efficiency was left intact in transgenic rats. Our results bring new knowledge on executive impairments and impact of emotional state on decision-making at different stages of the disease, increasing the face-validity of the BACHD rat model.


Risk factors and interventions for developing recurrent pneumonia in older adults.
Pneumonia is common among older adults and often recurrent. Several studies have been conducted on the risk factors for pneumonia; however, little is known about the risk factors for recurrent pneumonia. This study aimed to identify the risk factors for developing recurrent pneumonia among older adults and to investigate methods of prevention. We analysed the data of 256 patients aged 75 years or older who were admitted for pneumonia between June 2014 and May 2017. Moreover, we reviewed the medical records for the subsequent 3 years and defined the readmission caused by pneumonia as recurrent pneumonia. Risk factors for recurrent pneumonia were analysed using multivariable logistic regression analysis. Differences in the recurrence rate based on the types and use of hypnotics were also evaluated. Of the 256 patients, 90 (35.2%) experienced recurrent pneumonia. A low body mass index (OR: 0.91; 95% CI: 0.83‒0.99), history of pneumonia (OR: 2.71; 95% CI: 1.23‒6.13), lung disease as a comorbidity (OR: 4.73; 95% CI: 2.13‒11.60), taking hypnotics (OR: 2.16; 95% CI: 1.18‒4.01) and taking histamine-1 receptor antagonist (H1RA) (OR: 2.38; 95% CI: 1.07‒5.39) were risk factors. Patients taking benzodiazepine as hypnotics were more likely to experience recurrent pneumonia than patients not taking hypnotics (OR: 2.29; 95% CI: 1.25-4.18). We identified several risk factors for recurrent pneumonia. Among them, restricting the use of H1RA and hypnotics, in particular benzodiazepines, may be useful in preventing the recurrence of pneumonia in adults aged 75 years or older.


Crossreactivity between human and canine Ia antigens using a mouse monoclonal antibody (CIA).
A mouse monoclonal antibody (CIA) produced against human Ia antigens that reacts with 20-30% of human peripheral blood lymphocytes was found to react with more than 90% of dog lymphocytes. Less than 41% of the Ia-positive dog lymphocytes expressed surface immunoglobulins. Immunoprecipitation studies with 125I-labeled cells precipitated heavily labeled Ia bands at 28K and 35K from human cells, but from dog cells the 29K beta chain of Ia was much more heavily labeled than the alpha chain.


Ectopic adrenocorticotrophic hormone syndrome. A case report.
Excessive production of adrenocorticotrophic hormone (ACTH) by oat cell carcinomas and carcinoid tumours of the lung has been well documented. Florid cases of Cushing's syndrome secondary to the excessive production of ACTH by the tumour are rare. In this article 2 cases of florid Cushing's syndrome associated with oat cell carcinoma are described.


Determination of the complete three-dimensional structure of the alpha-amylase inhibitor tendamistat in aqueous solution by nuclear magnetic resonance and distance geometry.
The complete three-dimensional structure of the alpha-amylase inhibitor Tendamistat in aqueous solution was determined by 1H nuclear magnetic resonance and distance geometry calculations using the program DISMAN. Compared to an earlier, preliminary determination of the polypeptide backbone conformation, stereo-specific assignments were obtained for 41 of the 89 prochiral groups in the protein, and a much more extensive set of experimental constraints was collected, including 842 distance constraints from nuclear Overhauser effects and over 100 supplementary constraints from spin-spin coupling constants and the identification of intramolecular hydrogen bonds. The complete protein molecule, including the amino acid side-chains is characterized by a group of nine structures corresponding to the results of the nine DISMAN calculations with minimal residual error functions. The average of the pairwise minimal root-mean-square distances among these nine structures is 0.85 A for the polypeptide backbone, and 1.52 A for all the heavy atoms. The procedures used for the structure determination are described and a detailed analysis is presented of correlations between the experimental input data and the precision of the structure determination.


Folic acid-modified bovine serum albumin nanoparticles with doxorubicin and chlorin e6 for effective combinational chemo-photodynamic therapy.
We herein describe a facile method to synthesize stable bovine serum albumin-based nanoparticles (BNPs) loaded with two anticancer therapeutics, doxorubicin (DOX) and a photosensitizer, chlorin e6 (Ce6), in combination with folic acid (FA) as a target cancer cell receptor for the development of an effective combined chemo and photodynamic (FA-Ce6/DOX/BNPs) therapy against cervical cancer. FA-Ce6/DOX/BNPs exhibited excellent monodispersity with an average diameter of 103.5 ± 3.8 nm, a negative zeta potential of approximately -30.44 ± 0.35 mV, and long-term stability. As a result, FA-Ce6/DOX/BNPs exhibited severe toxicity to cervical HeLa cancer cells. Also, a higher drug release rate was observed under acidic pH conditions (pH 5.0). Moreover, FA-Ce6/DOX/BNPs potentiated mitochondrial reactive oxygen species (ROS) production in HeLa cells under 671-nm laser exposure, leading to activation of key regulator proteins of apoptosis such as BH3 interacting-domain death agonist (BID), B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X (BAX), as well as induction of the caspase cascade and mitochondrial ROS-mediated cell death. Confocal microscopy analysis further validated cellular uptake of FA-Ce6/DOX/BNPs by HeLa cells. Furthermore, results of real-time quantitative PCR (RT-qPCR) and western blot analysis further validated the anticancer effect of FA-Ce6/DOX/BNPs, as evidenced by elevated gene/protein expression levels of apoptotic biomarkers p53, BID, caspase-3, cleaved poly(ADP-ribose) polymerase 1 (PARP-1), and BAX, contrary to levels of the anti-apoptotic marker Bcl-2. Moreover, in vivo toxicity results of FA-Ce6/DOX/BNPs using laser irradiation in zebrafish larvae, as a chemo-photodynamic therapy confirmed that it does not affect the larval development without causing any adverse toxic effect in zebrafish larvae. Altogether these findings strongly support the anticancer effect of FA-Ce6/DOX/BNPs combinational chemo-photodynamic therapy, which could be a promising candidate for cervical cancer therapy.


Assessment of Homologous Recombination Deficiency in Ovarian Cancer.
Accurately assessing homologous recombination deficiency (HRD) to use as a predictive biomarker is an area of intense research in ovarian cancer. Validated assays have demonstrated utility in determining maintenance therapy following platinum sensitive chemotherapy. Novel functional assays promise the potential to reflect HRD in real time and predict response to PARP inhibitors. See related articles by Pikkusaari et al., p. 3110 and Blanc-Durand et al., p. 3124.


The effect of parenteral nutrition with different lipid emulsions on platelets.
This study investigated the effect of parenteral nutrition including 500 ml/day of two different lipid emulsions on platelet numbers and platelet aggregation. One lipid contained 20% long chain triglycerides, the other a mixture of 10% medium chain triglycerides and 10% long chain triglycerides. After 7-10 days parenteral feeding, platelet numbers had not changed significantly, platelet morphology appeared normal and the prothrombin time was unaltered. Platelet aggregation in response to varying concentrations of ADP, adrenaline and collagen was not significantly different from pre-feeding and was similar in patients receiving the two different lipids.


The relationship of the round window membrane to the cochlear aqueduct shown in three-dimensional imaging.
The round window membrane and cochlear aqueduct complex in the guinea pig are reconstructed with 3D-imaging, using orthogonal plane fluorescence optical sectioning (OPFOS). The 3D-images show that the periotic duct and the aqueduct are connected to a pouch-like extension of the round window. The function of this may be regulation of aqueduct flow resistance under the influence of a pressure difference between inner ear fluid and middle ear.


Diffuse Calvarial Hyperostosis in Patients with Spontaneous Intracranial Hypotension.
Diagnosis of spontaneous intracranial hypotension (SIH) may be delayed due to nonspecific symptoms and variable imaging findings. Cases of hyperostosis in children who are overshunted, a process that may be physiologically analogous to adults with SIH, have been reported by others and observed in our practice. The purpose of this retrospective study was to assess the frequency and pattern of calvarial hyperostosis in patients with SIH. We retrospectively reviewed computed tomography and magnetic resonance imaging examinations from consecutive patients who underwent myelography for the evaluation of SIH to assess for the presence of generalized calvarial thickening or development of a secondary layer of bone. Patients with typical benign hyperostosis frontalis were excluded. Patient demographics and clinical factors were evaluated for association with hyperostosis. Among 285 patients with SIH, 40 (14.0%) demonstrated diffuse calvarial hyperostosis on imaging. Most of these patients (32/40; 80.0%) demonstrated a distinct circumferentially layered appearance to the skull, whereas 8 of 40 (20.0%) had generalized calvarial thickening without layering. Diffuse calvarial hyperostosis, particularly the concentrically layered form that we term "layer cake skull," is a relatively common imaging feature in patients with SIH. In the appropriate clinical context, this finding will allow the possibility of SIH to be raised based on computed tomography imaging, which is otherwise of limited utility in the initial diagnosis of this condition.


pssRNAMiner: a plant short small RNA regulatory cascade analysis server.
In plants, short RNAs including approximately 21-nt microRNA (miRNA) and 21-nt trans-acting siRNA (ta-siRNA) compose a 'miRNA --> ta-siRNA --> target gene' cascade pathway that regulates gene expression at the posttranscriptional level. In this cascade, biogenesis of ta-siRNA clusters requires 21-nt intervals (i.e. phasing) and miRNA (phase-initiator) cleavage sites on its TAS transcript. Here, we report a novel web server, pssRNAMiner, which is developed to identify both the clusters of phased small RNAs as well as the potential phase-initiator. To detect phased small RNA clusters, the pssRNAMiner maps input small RNAs against user-specified transcript/genomic sequences, and then identifies phased small RNA clusters by evaluating P-values of hypergeometric distribution. To identify potential phase-initiators, pssRNAMiner aligns input phase-initiators with transcripts of TAS candidates using the Smith-Waterman algorithm. Potential cleavage sites on TAS candidates are further identified from complementary regions by weighting the alignment expectation and its distance to detected phased small RNA clusters. The pssRNAMiner web server is freely available at http://bioinfo3.noble.org/pssRNAMiner/.


Stroke education: retention effects in those at low- and high-risk of stroke.
Relatively few studies have tracked retention effects of stroke education in low- and high-risk groups. Such information is important to improve the design of stroke prevention programs. The frequency of risk factors within the sample was defined as "high" if 30% or more of participants in that group had that risk. Only one stroke risk factor was present at this level in the low-risk group (n=29; all less than 50 years old). The high-risk group was 44 individuals aged 50 years or over, with four stroke risk factors present at this level. Stroke knowledge was tested on three occasions: baseline, post-education, and retention. Education consisted of reading a published stroke brochure. Stroke knowledge improved over time, from baseline to post-education, but not from post-education to retention. The performance of both groups increased, but there was a differential learning effect: low-risk participants learned more than high-risk participants. Important information was learned and included details such when TIA symptoms dissipate. This particular issue was one about which both groups knew little at baseline (less than 15% of combined sample answered this item correctly), but post-education at least 75% of participants got this question correct. Both low- and high-risk individuals can learn information about stroke and retain it over the short term. The "durable" effects in learning observed in this study are important because the benefit of brochure-only approaches to education have not yet been convincingly demonstrated. Information about stroke from education brochures is retained by at-risk populations for at least 1 week.


Systolic functional response of normal older and younger adult left ventricles to beta-blockade during exercise.
There is controversy over the effects of beta-blockade on the left ventricular systolic response of the heart of the elderly to stress. In this study we compared the effects of acute beta-blockade in normal older and younger adult left ventricles during exercise. The study population consisted of 17 healthy elderly people, 67 +/- 3 years old, while 18 young normal subjects, 31 +/- 4 years old, served as controls. A symptom-limited exercise treadmill test was performed before and 15 minutes after intravenous administration of 0.12 mg propranolol/kg. M-mode echocardiographic studies were performed before and immediately after each test. Intravenous propranolol at rest decreased heart rate by 14 +/- 7 beats/min in the elderly and by 7.5 +/- 8 beats/min in the young (p = 0.02), decreased the double product by 2500 +/- 1200 mmHg/min and 1830 +/- 970 mmHg/min (p = 0.05), respectively; changed the left ventricular end-systolic dimension by +0.21 +/- 0.36 cm and +0.03 +/- 0.24 cm (p = 0.09), respectively; and changed the end-diastolic dimension by +0.22 +/- 0.46 cm in the elderly and by -0.02 +/- 0.32 cm in the young (p = 0.08). The change in fractional shortening was -1.22 +/- 4.17% in the elderly and -0.78 +/- 4.05% in the young (p > 0.05), and the decrease in the systolic blood pressure/end-systolic dimension ratio was 5.9 +/- 7 mmHg/cm and 4.3 +/- 3.8 mmHg/cm, respectively (p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Circumferential intimal tear causing obstruction of the aortic arch: an unusual complication of aortic dissection.
A 66-year-old man was first seen because of occlusive disease of the aortic arch vessels secondary to a Type I aortic dissection. At operation, circumferential detachment of the intima was found with intussusception of this flap into the descending aorta causing obliteration of the arch vessels. There has been only one previous report of circumferential intimal intussusception complicating aortic dissection.


Impaired release of vitamin A from liver in primary biliary cirrhosis.
In 44 patients with primary biliary cirrhosis serum levels of vitamin A, retinol-binding protein and transthyretin (prealbumin) were found to be significantly lower than in 25 sex- and age-matched controls. Liver biopsies were available for chemical analyses in 28 of the patients. Their mean liver vitamin A concentration (2.8 +/- 2.0 mumoles per gm wet weight) did not differ significantly from that in 22 cases of sudden death which served as controls (2.0 +/- 1.5 mumoles per gm wet weight). Immunohistochemical investigation showed a normal distribution of serum retinol-binding protein in the patients' livers, whereas the staining pattern of cellular retinol-binding protein, believed to be involved in the intrahepatic transport of vitamin A, was abnormal. Thus, the number size and cellular retinol-binding protein staining intensity of fat-storing (Ito) cells were clearly higher in the patients as compared with controls. The results suggest that the low serum vitamin A levels in primary biliary cirrhosis are not a consequence of vitamin A deficiency but instead reflect a defective mobilization of vitamin A from the liver.


Effect of verapamil on basal and pentagastrin-stimulated gastric acid secretion.
The role of calcium in gastric acid secretion is still uncertain. The effect of verapamil on basal and pentagastrin-stimulated gastric acid secretion was evaluated in eight normal men. Submaximal pentagastrin tests (2 micrograms/kg/hr) were performed after pretreatment with intravenous verapamil at a concentration of 0.1 mg/kg and followed 1 hr later with a second bolus injection of 0.15 mg/kg. On a separate day, subjects received a placebo injection of saline solution at the same designated times as the verapamil. Verapamil did not alter basal or stimulated gastric acid secretion. All subjects showed ECG evidence of significant calcium-channel blocking (i.e., prolongation of PR interval). Data indicate that therapeutic doses of a calcium slow-channel antagonist do not alter gastric acid secretion in normal subjects. Results support the concept that in vivo, secretory function of the human parietal cell is not affected by alteration in cellular calcium flux.


Wnt signaling pathway improves central inhibitory synaptic transmission in a mouse model of Duchenne muscular dystrophy.
The dystrophin-associated glycoprotein complex (DGC) that connects the cytoskeleton, plasma membrane and the extracellular matrix has been related to the maintenance and stabilization of channels and synaptic receptors, which are both essential for synaptogenesis and synaptic transmission. The dystrophin-deficient (mdx) mouse model of Duchenne muscular dystrophy (DMD) exhibits a significant reduction in hippocampal GABA efficacy, which may underlie the altered synaptic function and abnormal hippocampal long-term plasticity exhibited by mdx mice. Emerging studies have implicated Wnt signaling in the modulation of synaptic efficacy, neuronal plasticity and cognitive function. We report here that the activation of the non-canonical Wnt-5a pathway and Andrographolide, improves hippocampal mdx GABAergic efficacy by increasing the number of inhibitory synapses and GABA(A) receptors or GABA release. These results indicate that Wnt signaling modulates GABA synaptic efficacy and could be a promising novel target for DMD cognitive therapy.


Induction of HLA-G expression in a melanoma cell line OCM-1A following the treatment with 5-aza-2'-deoxycytidine.
The non-classical HLA class I antigen HLA-G is an immune modulator which inhibits the functions of T cells, NK cells, and the Dendritic cells (DC). As a result, HLA-G expression in malignant cells may provide them with a mechanism to escape the immune surveillance. In melanoma, HLA-G antigen expression has been found in 30% of surgically removed lesions but in less than 1% of established cell lines. One possible mechanism underlying the differential HLA-G expression in vivo and in vitro is that the HLA-G gene is epigenetically repressed in melanoma cells in vitro. To test this hypothesis, we treated the HLA-G negative melanoma cell line OCM-1A with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-AC) and analyzed whether HLA-G expression can be restored. Our data strongly suggest that HLA-G is silenced as a result of CpG hypermethylation within a 5' regulatory region encompassing 220 bp upstream of the start codon. After treatment, HLA-G mRNA expression was dramatically increased. Western blot and flow cytometry showed that HLA-G protein was induced. Interestingly, HLA-G cell surface expression on the 5-AC treated OCM-1A cells is much less than that on the HLA-G positive JEG-3 cells while a similar amount of total HLA-G was observed. Possible mechanisms for the difference were analyzed in the study such as cell cold-treatment, peptide loading and antigen processing machinery components (APM) as well as beta2 microglobulin (beta2-m) expression. Data revealed that the APM component calreticulin might be involved in the lower HLA-G surface expression on OCM-1A cells. Taken together, our results indicated that DNA methylation is an important epigenetic mechanism by which HLA-G antigen expression is modulated in melanoma cells in vitro. Furthermore, to the first time, we hypothesized that the deficiency of calreticulin might be involved in the low HLA-G surface expression on the 5-AC treated OCM-1A cells.


Parents of older at-risk youth: a retention challenge for preventive intervention.
We examined data from 162 families who participated in the prevention program Parents and Youth with Schools, which targeted at-risk high school youth and parents, to understand parent retention in the 15-session Parents as Partners program. We obtained reports from youth, parents and parent interventionists, which included both time-invariant and time-varying data regarding demographic factors; parent, youth and family characteristics; and parents' response to intervention. Utilizing event history analysis, we examined data sequentially in order to determine those variables that predicted continued parent attendance. In the model examining all areas simultaneously, the predictors of parent retention across the full program were parent minority status and age, teen anger and parent-teen conflict over school attendance, as well as parents' reports of group support and interventionists' report of parents' commitment. Overall, the analyses indicated that participants' characteristics, as well as their measureable response to the intervention, can alert researchers to potential program disengagement. Monitoring indicators of disengagement will help researchers focus resources early in the intervention process in order to maximize parent attendance and increase the success of prevention programs.


High-dose adjuvant interferon therapy for melanoma.
High-dose interferon has recently been approved as an adjuvant to surgery for treating newly diagnosed patients at high-risk for melanoma, particularly those with regional lymph node disease. The data supporting the indications for treatment and its side effects are reviewed.


Serial changes in plasma levels of pancreatic elastase 1 after pancreatic surgeries.
The alterations of the plasma level of elastase 1 (Ela) were investigated in 15 patients undergoing total pancreatectomy (TP), 18 patients undergoing pancreatoduodenectomy (PD), 8 patients undergoing distal pancreatectomy (DP) and 10 patients undergoing gastrectomy for gastric cancer (GR). The Ela level decreased rapidly below the normal level after TP. The plasma half-life of Ela was 4.6 +/- 1.2 h (Mean +/- SEM). The Ela levels after PD were abnormally elevated until the 7th postoperative day. The Ela levels after DP and GR were elevated gradually until the 7th postoperative day. From 1 to 6 months after PD, DP and GR, the Ela levels were normal. An additional release of Ela from the remaining pancreas following direct surgical interventions to the pancreas resulted in the elevated of the plasma level of Ela in the early postoperative period. The plasma level of Ela was normalized within 2 weeks after pancreatic surgery.


Sociodemographic factors affecting paediatric surgical training in Malaysia: Gender matters.
A shortage of specialist paediatric surgeons in Malaysia led to establishment of a national postgraduate training programme in 2004. We aimed to identify sociodemographic factors impacting training experience, and to define pressure points during training to inform targeted trainee support strategies. We conducted an anonymized online survey in June 2021 on all programme graduates. Participants were asked for sociodemographic data, both current and during training. Likert scale responses were required for questions regarding adequacy of support received for family, health and personal issues during training. A free text response question soliciting suggestions for programme improvement was included. Data are reported as median (range). Chi-square/Fisher's exact tests for categorical variables and Mann-Whitney U tests for continuous variables were used, with p<0.05 significance. Of 53 eligible participants, 52 (98%) responded, 24 (46%) were female. Marital status was similar between genders at entry, but female trainees were more likely to be unmarried on exit (p = 0.001), and less likely to have children while training (p = 0.017). Of the 6 female and 18 male trainees who had children while training, women were more likely to take parental leave (p = 0.01). The majority felt advice given regarding parental leave and managing training while having children were poor. In thematic analysis of free text answers, lack of hands-on experience was the most common concern. Factors related to marriage and parenthood significantly associate with gender amongst trainees in Malaysia despite both genders being well represented. Concerns regarding adequacy of hands-on training highlight the need for educational innovations such as simulation models. Level III.


Intranasal administration of diphtheria toxoid. Selecting antibody isotypes using formulations having various lipophilic characteristics.
Non-ionic excipients, having different lipophilicity, were compared for their selection of immunological response in different organs and biological fluids. In order to express the lipophilicity of the formulation, the balance between the size and strength of the hydrophilic and lipophilic groups was used, called the hydrophile-lipophile balance (HLB) value. Mice were immunized and boosted intranasally with diphtheria toxoid, and samples were taken from the blood, spleen, nasal wash, lungs, saliva, stomach, duodenum, jejunum and the skin. In general, formulations which were highly hydrophilic and highly lipophilic were not able to augment the immunological response markedly (except for IgA). Formulations having intermediate HLB values, e.g. around 9.0, stimulated both IgG1 and IgG2a production, where the HLB = 5.5 formulation seemed to stimulate mainly IgG2b and IgG3 antibody production. On the other hand, comparing the IgA concentration in various samples with respective IgG level, increasing HLB value seems to augment the production of mainly IgA antibodies. The results indicate that the antibody isotypes may be controlled, using variations in the hydrophile-lipophile balance value.


New indolizine-chalcones as potent inhibitors of human farnesyltransferase: Design, synthesis and biological evaluation.
A new family of indolizine-chalcones was designed, synthesized and screened for the inhibitory potential on human farnesyltransferase in vitro to identify potent antitumor agents. The most active compound was phenothiazine 2a, exhibiting an IC50 value in the low nanomolar range, similar to that of known FTI-276, highly potent farnesyltransferase inhibitor. The newly synthesized indolizine-chalcones 2a-d constitute the most efficient inhibitors of farnesyltransferase bearing a phenothiazine unit known to date.


Absorption of minoxidil after topical application: effect of frequency and site of application.
The effect of application site and frequency on the systemic absorption of topical minoxidil was studied in 52 normal men. Subjects received 1 ml 3% minoxidil solution applied four, six, or eight times daily to the scalp or two, four, six, or eight times daily to the chest for 14 days. Serum and urine were collected and analyzed for minoxidil. No systemic minoxidil accumulation occurred from increasing application frequency to the scalp. Trends in the chest data suggest that absorption may have been lower with the twice-daily regimen. Absorption through the scalp and chest were similar for the lower-frequency regimens; however, trends in the eight-times-a-day regimens suggest that absorption may have been somewhat greater from application to the scalp. Systemic minoxidil accumulation resulting from frequent application is unlikely. The initial dose probably saturates the skin for a period of time longer than the dosing intervals examined.


Genetic determinants of vascular remodelling.
Vascular remodelling is an important physiological mechanism that occurs as a result of changes in hemodynamics, and is a pathological process that plays a major role in the clinical manifestations of cardiovascular diseases. Using a mouse model, it was recently established that vascular remodelling is partially based on ligation of the carotid. In this model, low flow was associated with intima media thickening (IMT). IMT is a major manifestation of atherosclerosis of the carotid artery, and it is an important predictor of cardiovascular events. Carotid IMT has a strong genetic component. It was hypothesized that there would be genetically determined differences in outward remodelling and IMT induced by carotid flow alterations. Vascular remodelling among five inbred strains of mice were compared. Despite similar changes in flow in the left carotid among the strains, dramatic differences in remodelling of the partially ligated left carotid relative to control were observed. IMT correlated significantly with heart rate, outward remodelling and changes in plasminogen activator expression, cell proliferation and apoptosis. There were significant strain-dependent differences in the remodelling index (measured as the ratio of vessel area to IMT), which suggest fundamental alterations in sensing or transducing hemodynamic signals among strains. This model should be useful to identify and characterize the role of genes that mediate vascular remodelling.


Combined Autologous Adductor Magnus and Partial Quadriceps Tendon Technique for Medial Patellofemoral Ligament Reconstruction and Cellularized Scaffold Implantation of the Patella.
There are many studies in the literature on the use of adductor magnus and quadriceps tendons in primary or revision surgery of patellofemoral instability in skeletally immature patients. In this Technical Note, the combination of both tendons is presented with cellularized scaffold implantation cartilage surgery in the patella.


Early results of local application of 13-cis retinoic acid in the treatment of leukoplakia of the vulva.
A group of 35 patients with leukoplakia of the vulva was treated with 13-cis retinoic acid applied topically. Complete or partial remission occurred in 17 patients. Parallel determination of retinol level in sera revealed its increased value as compared to healthy persons.


The phosphonopyruvate decarboxylase from Bacteroides fragilis.
The Bacteroides fragilis capsular polysaccharide complex is the major virulence factor for abscess formation in human hosts. Polysaccharide B of this complex contains a 2-aminoethylphosphonate functional group. This functional group is synthesized in three steps, one of which is catalyzed by phosphonopyruvate decarboxylase. In this paper, we report the cloning and overexpression of the B. fragilis phosphonopyruvate decarboxylase gene (aepY), purification of the phosphonopyruvate decarboxylase recombinant protein, and the extensive characterization of the reaction that it catalyzes. The homotrimeric (41,184-Da subunit) phosphonopyruvate decarboxylase catalyzes (kcat = 10.2 +/- 0.3 s-1) the decarboxylation of phosphonopyruvate (Km = 3.2 +/- 0.2 microm) to phosphonoacetaldehyde (Ki = 15 +/- 2 microm) and carbon dioxide at an optimal pH range of 7.0-7.5. Thiamine pyrophosphate (Km = 13 +/- 2 microm) and certain divalent metal ions (Mg(II) Km = 82 +/- 8 microm; Mn(II) Km = 13 +/- 1 microm; Ca(II) Km = 78 +/- 6 microm) serve as cofactors. Phosphonopyruvate decarboxylase is a member of the alpha-ketodecarboxylase family that includes sulfopyruvate decarboxylase, acetohydroxy acid synthase/acetolactate synthase, benzoylformate decarboxylase, glyoxylate carboligase, indole pyruvate decarboxylase, pyruvate decarboxylase, the acetyl phosphate-producing pyruvate oxidase, and the acetate-producing pyruvate oxidase. The Mg(II) binding residue Asp-260, which is located within the thiamine pyrophosphate binding motif of the alpha-ketodecarboxylase family, was shown by site-directed mutagenesis to play an important role in catalysis. Pyruvate (kcat = 0.05 s-1, Km = 25 mm) and sulfopyruvate (kcat approximately 0.05 s-1; Ki = 200 +/- 20 microm) are slow substrates for the phosphonopyruvate decarboxylase, indicating that this enzyme is promiscuous.


Evaluation of gait characteristics in subjects with locomotive syndrome using wearable gait sensors.
Individuals with locomotive syndrome (LS) require nursing care services owing to problems with locomotion and the musculoskeletal system. Individuals with LS generally have a reduced walking speed compared with those without LS. However, differences in lower-limb kinematics and gait between individuals with and without LS are not fully understood. This study aimed to clarify the characteristics of the gait kinematics of individuals with LS using wearable sensors. We assessed 125 participants (mean age 73.0 ± 6.7 years) who used a public health promotion facility. Based on the 25-question Geriatric Locomotive Function Scale (GLFS-25), these participants were grouped into the non-LS (GLFS-25 < 7), LS-stage 1 (GLFS-25 7-16), and LS-stage 2 (GLFS-25 ≥ 16) groups (larger GLFS-25 scores indicate worse locomotive ability). Spatiotemporal parameters and lower-limb kinematics during the 10-m walk test were analyzed by the "H-Gait system", which is a motion analysis system that was developed by the authors and is based on seven inertial sensors. The peak joint angles during the stance and swing phases, as well as the gait speed, cadence, and step length were compared among all groups. There were 69 participants in the non-LS group, 33 in the LS-stage 1 group, and 23 in the LS-stage 2 group. Compared with the non-LS group, the LS-stage 2 group showed significantly smaller peak angles of hip extension (9.5 ± 5.3° vs 4.2 ± 8.2°, P = 0.002), hip flexion (34.2 ± 8.8° vs 28.5 ± 9.5°, P = 0.026), and knee flexion (65.2 ± 18.7° vs 50.6 ± 18.5°, P = 0.005). The LS-stage 1 and LS-stage 2 groups had a significantly slower mean gait speed than the non-LS group (non-LS: 1.3 ± 0.2 m/s, LS-stage 1: 1.2 ± 0.2 m/s, LS-stage 2: 1.1 ± 0.2 m/s, P < 0.001). The LS-stage 2 group showed significantly different lower-limb kinematics compared with the non-LS group, including smaller peak angles of hip extension, hip flexion, and knee flexion. It would be useful to assess and improve these small peak joint angles during gait for individuals classified as LS-stage 2.


Defibrillation.
The field of defibrillation is one of the most rapidly advancing areas in resuscitation. Defibrillation is also one of the most promising interventions for achieving improved survival from cardiac arrest. The purpose of this article is to provide an overview of the science and clinical applications of defibrillation.


iPSC-derived mesenchymal stem cells attenuate cerebral ischemia-reperfusion injury by inhibiting inflammatory signaling and oxidative stress.
Induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs) hold great promise as a cell source for transplantation into injured tissues to alleviate inflammation. However, the therapeutic efficacy of iMSC transplantation for ischemic stroke remains unknown. In this study, we evaluated the therapeutic effects of iMSC transplantation on brain injury after ischemia-reperfusion using a rat transient middle cerebral artery occlusion model and compared its therapeutic efficacy with that of bone marrow mesenchymal stem cells (BMMSCs). We showed that iMSCs and BMMSCs reduced infarct volumes after reperfusion and significantly improved motor function on days 3, 7, 14, 28, and 56 and cognitive function on days 28 and 56 after reperfusion compared with the vehicle group. Furthermore, immunological analyses revealed that transplantation of iMSCs and BMMSCs inhibited microglial activation and expression of proinflammatory cytokines and suppressed oxidative stress and neuronal cell death in the cerebral cortex at the ischemic border zone. No difference in therapeutic effect was observed between the iMSC and BMMSC groups. Taken together, our results demonstrate that iMSC therapy can be a practical alternative as a cell source for attenuation of brain injury and improvement of neurological function because of the unlimited supply of uniform therapeutic cells.


A mild form of Stickler syndrome type II caused by mosaicism of COL11A1.
Stickler syndrome, a clinically as well as molecularly heterogeneous connective tissue disorder, is predominantly inherited in an autosomal dominant manner and is considered complete penetrant. Previously, mosaicism in Stickler syndrome has been reported in only a few cases. We describe a child with Stickler syndrome due to a novel splice site mutation in COL11A1. Initially, Sanger sequencing of both parents showed normal test results for the mutation. Due to mild phenotypic traits, the father was tested again using a more sensitive method (NGS), and was found to have low-grade mosaicism in various tissue samples (range 7-22% of the DNA). Therefore, we recommend using sensitive genetic testing when mosaicism is suspected. Furthermore, we support previous suggestions of parental testing even when the parents of an affected patient do not have obvious phenotypic signs of Stickler syndrome.


AMI Salon: AMI Salon Award Winners - Atlanta, Georgia.
This issues Gallery features the award winning imagery from AMI's 2016 Salon exhibition in Atlanta, Georgia.


Low serotonin1B receptor binding potential in the anterior cingulate cortex in drug-free patients with recurrent major depressive disorder.
The pathophysiology of major depressive disorder (MDD) is not fully understood and the diagnosis is largely based on history and clinical examination. So far, several lines of preclinical data and a single imaging study implicate a role for the serotonin1B (5-HT1B) receptor subtype. We sought to study 5-HT1B receptor binding in brain regions of reported relevance in patients with MDD. Subjects were examined at the Karolinska Institutet PET centre using positron emission tomography (PET) and the 5-HT1B receptor selective radioligand [(11)C]AZ10419369. Ten drug-free patients with recurrent MDD and ten control subjects matched for age and sex were examined. The main outcome measure was [(11)C]AZ10419369 binding in brain regions of reported relevance in the pathophysiology of MDD. The [(11)C]AZ10419369 binding potential was significantly lower in the MDD group compared with the healthy control group in the anterior cingulate cortex (20% between-group difference), the subgenual prefrontal cortex (17% between-group difference), and in the hippocampus (32% between-group difference). The low anterior cingulate [(11)C]AZ10419369 binding potential in patients with recurrent MDD positions 5-HT1B receptor binding in this region as a putative biomarker for MDD and corroborate a role of the anterior cingulate cortex and associated areas in the pathophysiology of recurrent MDD.


Order and fluidity in the terminal methyl region of dipalmitoyl phosphatidylcholine multibilayers: a comparison of Raman and 2H-NMR spectroscopy.
Deuterium magnetic resonance (2H-NMR) and Raman spectroscopy are used to investigate order and fluidity at the terminal methyl position in 16-d3, 16'-d3 dipalmitoylphosphatidyl-choline (16-d6 DPPC) multibilayers. These methods reveal substantial motion and disorder in the gel phase, 5-10 degree C below the gel-liquid crystal phase transition temperature (Tm). The phase transition is sensed in the 2H-NMR spectrum as a reduction in the quadrupole splitting from 14 kHz to approximately 3 kHz. In contrast, the Raman parameter used to characterize the CD3 vibrations is quite insensitive to the melting process, although an analagous parameter does sense disordering at Tm at the 10 and 10' position in 10-d2, 10'-d2 DPPC. The difference in the response of the NMR and Raman parameters may arise because the vibrational spectrum of the CD3 group is inhomogeneously broadened and is therefore quite sensitive to alterations in the local environment around the methyl group. In contrast, the NMR quadrupole splitting is sensitive to both local motion of the methyl group and, near Tm, to motions of the CD2 group induced by transgauche isomerizations further up the chain. The difficulties that arise when results from different spectroscopic techniques are compared are demonstrated.


Modeling real shim fields for very high degree (and order) B0 shimming of the human brain at 9.4 T.
To describe the process of calibrating a B0 shim system using high-degree (or high order) spherical harmonic models of the measured shim fields, to provide a method that considers amplitude dependency of these models, and to show the advantage of very high-degree B0 shimming for whole-brain and single-slice applications at 9.4 Tesla (T). An insert shim with up to fourth and partial fifth/sixth degree (order) spherical harmonics was used with a Siemens 9.4T scanner. Each shim field was measured and modeled as input for the shimming algorithm. Optimal shim currents can therefore be calculated in a single iteration. A range of shim currents was used in the modeling to account for possible amplitude nonlinearities. The modeled shim fields were used to compare different degrees of whole-brain B0 shimming on healthy subjects. The ideal shim fields did not correctly shim the subject brains. However, using the modeled shim fields improved the B0 homogeneity from 55.1 (second degree) to 44.68 Hz (partial fifth/sixth degree) on the whole brains of 9 healthy volunteers, with a total applied current of 0.77 and 6.8 A, respectively. The necessity of calibrating the shim system was shown. Better B0 homogeneity drastically reduces signal dropout and distortions for echo-planar imaging, and significantly improves the linewidths of MR spectroscopy imaging. Magn Reson Med 79:529-540, 2018. © 2017 International Society for Magnetic Resonance in Medicine.


Metal free thiol-maleimide 'Click' reaction as a mild functionalisation strategy for degradable polymers.
The stoichiometric reaction between thiols and maleimide-functional poly(ester)s is demonstrated to be a quantitative, tolerant, mild and efficient method for polymer modification.


The impact of empirical hydrocortisone therapy on clinical outcomes in dengue fever: a retrospective chart review.
The role of steroids in dengue infection (DI) remains uncertain. A retrospective chart review was conducted on patients ≥18 y of age diagnosed with DI based on positivity for dengue non-structural antigen 1 or immunoglobulin M between October 2017 and November 2018. Hydrocortisone was administered to 106 of 406 patients. DI with warning signs occurred in nine patients (9.5%) in the steroid cohort and eight patients (2.5%) in the non-steroid group. The incidence of severe DI, bleeding and admission duration were similar between the groups. Our study shows no significant benefit of empirical steroids in DI.


Loneliness and Attitudes Toward Aloneness in Adolescence: A Person-Centered Approach.
In adolescence, feeling lonely and dealing with time spent alone become particularly salient. The present study examined the co-occurrence of parent- and peer-related loneliness, and positive and negative attitudes toward aloneness, using cluster analysis. In three independent samples, covering about 1800 adolescents (61 % female), six meaningful groups were identified. These groups showed different associations with adolescents' self-esteem and personality, parental responsiveness and psychological control, and peer group functioning and friendships. An adaptive pattern of correlates was found for adolescents in three of the six groups, that is, the Indifference group (with rather low scores on the four constructs), the Moderate group (with moderate scores on the four constructs), and the Negative Attitude Toward Aloneness group. A rather maladaptive pattern of correlates was found for adolescents in the three other groups, that is, the Peer-Related Loneliness group, the Positive Attitude Toward Aloneness group, and the Parent-Related Loneliness group. More specifically, adolescents in the Peer-Related Loneliness and Positive Attitude Toward Aloneness groups may need assistance regarding their relations with their peers, whereas adolescents in the Parent-Related Loneliness group may need assistance regarding their relations with their parents. Implications of these findings for current understanding and optimal measurement of adolescents' loneliness and aloneness are discussed.


Role of plectin and its interacting molecules in cancer.
Plectin, as the cytolinker and scaffolding protein, are widely expressed and abundant in many tissues, and has involved in various cellular activities contributing to tumorigenesis, such as cell adhesion, migration, and signal transduction. Due to the specific expression and differential localization of plectin in cancer, most researchers focus on the role of plectin in cancer, and it has emerged as a potent driver of malignant hallmarks in many human cancers, which provides the possibility for plectin to be widely used as a biomarker and therapeutic target in the early diagnosis and targeted drug delivery of the disease. However, there is still a lack of systematic review on the interaction molecules and mechanism of plectin. Herein, we summarized the structure, expression and function of plectin, and mainly focused on recent studies on the functional and physical interactions between plectin and its interacting molecules, shedding light on the potential of targeting plectin for cancer therapy.


Warning symbols as reminders of hazards: impact of training.
Prior research indicates that many warning symbols are poorly understood. However Lesch [Lesch, M.F., 2003. Comprehension and memory for warning symbols: Age-related differences and impact of training. J. Safety Res. 34, 495-505] found that accident scenarios could be used to improve comprehension of warning symbols. The current study further investigated the potential benefits of accident scenario training. During training, warning symbols with verbal labels corresponding to the meaning of the symbol were paired with accident scenarios which expanded on the nature of the hazard, the required/prohibited actions, as well as the possible consequences of failing to comply. A number of measures were obtained prior to, and following (immediately and 2 weeks later), the accident scenario training: comprehension across three knowledge types (verbal label, required/prohibited actions, potential consequences of failure to comply), ratings of agreement with statements reflecting perceived control, and ratings of hazard and intent to comply. Benefits of training were observed on all dependent measures: Comprehension improved from 43 to 82% correct, reaction times were reduced by about 2s, and level of confidence in correct responses increased by 23%. Ratings of perceived hazard, intent to comply, and perceived control over accident/injury involvement also increased. It is suggested that accident scenario training can be used to help prevent accidents and injuries by ensuring that responses to warnings are "sure and swift".