Effect of Activated Immunocompetent Cells on the Content of Multipotent Stromal Cells in Splenic Transplants of CBA and CBA/N Mice Administered with Polyvinylpyrrolidone.
One day after intraperitoneal injection of polyvinylpyrrolidone (PVP) to recipient CBA and CBA/N mice, the count of multipotent stromal cells (MSC) in the 4-month-old splenic transplants was minimum in CBA/N→CBA/N group in comparison with the transplants of intact recipients (0.6 from the control level), but increased by 2.3, 3.2, and 3.7 times in CBA/N→CBA, CBA→CBA, and CBA→CBA/N groups, respectively. In the blood serum of recipient CBA/N mice with 4-month splenic transplants of CBA donors, the levels of some cytokines (IL-5, TNFα, and IL-2) was significantly increased 1 and 24 h after PVP injection in contrast to mice with bone marrow transplants, which attests to activation of the innate immunity mechanisms in this (splenic) transplantation variant. Probably, this phenomenon can be explained by the fact that the splenic transplants contain a sufficient number of CD+B-1a lymphocytes that can restore the response of recipient CBA/N mice to PVP. Thus, similar to bone marrow transplants [5], MSC count in splenic transplants increased only in groups, where the recipients were capable of responding to PVP. In other words, after injection of PVP to recipient mice, MSC counts in the spleen and bone marrow at this moment are determined by availability of activated immunocompetent cells. Overall, the novel data attest to close relationships between the stromal tissue of hematopoietic and lymphoid organs, on the one hand, and immune system, on the other.


Co-exposure of avermectin and imidacloprid induces DNA damage, pyroptosis, and immune dysfunction in epithelioma papulosum cyprini cells via ROS-mediated Keap1/Nrf2/TXNIP axis.
Pesticide mixtures can reduce pest resistance, however, their overuse severely threatens aquatic animal survival and public health. Avermectin (AVM) and imidacloprid (IMI) are potent insecticides often employed in agriculture. By inducing oxidative stress, these chemicals can induce cell death. Here, we evaluated the combined toxicity of AVM and IMI on EPC cells based on the concept of toxicity units (TU). We established EPC cell models exposed to AVM and IMI alone and in combination. The results showed that AVM and IMI had additive effects on the toxicity of EPC cells. Meanwhile, the co-exposure of AVM and IMI exacerbated oxidative stress and induced excessive production of reactive oxygen species (ROS), triggered Keap1/Nrf2/TXNIP axis, caused DNA damage and increased the expression of genes related to pyroptosis. In addition, co-exposure to AVM and IMI caused immunosuppression of EPC cells. The ROS inhibitor N-Acetyl-l-cysteine (NAC) can dramatically reverse these alterations brought on by AVM and IMI co-exposure. The findings above conclude that co-exposure to AVM and IMI causes DNA damage, pyroptosis, and immunosuppression in EPC cells through the ROS-mediated Keap1/Nrf2/TXNIP pathway. This study revealed the joint toxicity of AVM and IMI on EPC cells, and reminded people to consider its impact on aquatic animals when using pesticide mixtures.


Developing and validating ultrasound-based radiomics models for predicting high-risk endometrial cancer.
The primary aim of this study was to develop and validate radiomics models, applied to ultrasound images, capable of differentiating from other cancers high-risk endometrial cancer, as defined jointly by the European Society for Medical Oncology, European Society of Gynaecological Oncology and European Society for Radiotherapy & Oncology (ESMO-ESGO-ESTRO) in 2016. The secondary aim was to develop and validate radiomics models for differentiating low-risk endometrial cancer from other endometrial cancers. This was a multicenter, retrospective, observational study. From two participating centers, we identified consecutive patients with histologically confirmed diagnosis of endometrial cancer who had undergone preoperative ultrasound examination by an experienced examiner between 2016 and 2019. Patients recruited in Center 1 (Rome) were included as the training set and patients enrolled in Center 2 (Milan) formed the external validation set. Radiomics analysis (extraction of a high number of quantitative features from medical images) was applied to the ultrasound images. Clinical (including preoperative biopsy), ultrasound and radiomics features that were statistically significantly different in the high-risk group vs the other groups and in the low-risk group vs the other groups on univariate analysis in the training set were considered for multivariate analysis and for developing ultrasound-based machine-learning risk-prediction models. For discriminating between the high-risk group and the other groups, a random forest model from the radiomics features (radiomics model), a binary logistic regression model from clinical and ultrasound features (clinical-ultrasound model) and another binary logistic regression model from clinical, ultrasound and previously selected radiomics features (mixed model) were created. Similar models were created for discriminating between the low-risk group and the other groups. The models developed in the training set were tested in the validation set. The performance of the models in discriminating between the high-risk group and the other groups, and between the low-risk group and the other risk groups for both validation and training sets was compared. The training set comprised 396 patients and the validation set 102 patients. In the validation set, for predicting high-risk endometrial cancer, the radiomics model had an area under the receiver-operating-characteristics curve (AUC) of 0.80, sensitivity of 58.7% and specificity of 85.7% (using the optimal risk cut-off of 0.41); the clinical-ultrasound model had an AUC of 0.90, sensitivity of 80.4% and specificity of 83.9% (using the optimal cut-off of 0.32); and the mixed model had an AUC of 0.88, sensitivity of 67.3% and specificity of 91.0% (using the optimal cut-off of 0.42). For the prediction of low-risk endometrial cancer, the radiomics model had an AUC of 0.71, sensitivity of 65.0% and specificity of 64.5% (using the optimal cut-off of 0.38); the clinical-ultrasound model had an AUC of 0.85, sensitivity of 70.0% and specificity of 80.6% (using the optimal cut-off of 0.46); and the mixed model had an AUC of 0.85, sensitivity of 87.5% and specificity of 72.5% (using the optimal cut-off of 0.36). Radiomics seems to have some ability to discriminate between low-risk endometrial cancer and other endometrial cancers and better ability to discriminate between high-risk endometrial cancer and other endometrial cancers. However, the addition of radiomics features to the clinical-ultrasound models did not result in any notable increase in performance. Other efficacy studies and further effectiveness studies are needed to validate the performance of the models. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.


BDNF pathway is involved in the protective effects of SS-31 on isoflurane-induced cognitive deficits in aging mice.
Mitochondrial dysfunction has been linked to the earliest pathogenesis of isoflurane-induced cognitive impairments in developing or aging mammalian brain. However, its molecular mechanism is poorly understood and a pharmacologic treatment to rapidly reverse mitochondrial dysfunction is lacking. Fifteen-month-old male C57BL/6 mice were exposed to isoflurane for two hours following intraperitoneal administration of mitochondrion-targeted peptide SS-31 or vehicle with 30min interval. The hippocampus was immediately removed for biochemical assays and mitochondria isolation after inhalation. Behavioral tests were evaluated by the open field test and fear conditioning test 24h after the experiment. We showed that cognitive deficits induced by exposure of the aging mice to isoflurane were accompanied by mitochondrial dysfunction in hippocampus due to loss of the enzymatic activity of complex I. This loss resulted in the increase of reactive oxygen species production, decrease of ATP production and mitochondrial membrane potential, and opening of mitochondrial permeability transition pore. Further, we provided evidence that the BDNF signaling pathway was involved in this process to regulate synaptic plasticity-related proteins, for instance, downregulation of synapsin 1, PSD-95 and p-CREB, and upregulation of NR2A, NR2B, CaMKIIα and CaMKIIβ. Of note, the isoflurane-induced cognitive deficits were rescued by SS-31 through reversal of mitochondrial dysfunction, which facilitated the regulation of BDNF signaling including the expression reversal of aforementioned important synaptic-signaling proteins in aging mice. Our data demonstrate that reversing mitochondrial dysfunction by SS-31 enhances BDNF signaling pathway and synaptic plasticity, and provides protective effects on cognitive function, thereby support the notion that SS-31 may have therapeutic benefits for elderly humans undertaking anesthesia.


Endogenous production of antimicrobial peptides in innate immunity and human disease.
Antimicrobial peptides are diverse and evolutionarily ancient molecules produced by all living organisms. Peptides belonging to the cathelicidin and defensin gene families exhibit an immune strategy as they defend against infection by inhibiting microbial survival, and modify hosts through triggering tissue-specific defense and repair events. A variety of processes have evolved in microbes to evade the action of antimicrobial peptides, including the ability to degrade or inactivate antimicrobial peptides, or suppress host production of the peptide in response to infection. Animal models and clinical investigations have shown that an absence of cathelicidin or defensin antimicrobials can lead to disease. In this article, we review important recent advances in understanding the biology of antimicrobial peptides and their role in normal immunity and human disease.


Evaluation of the optical properties of CAD-CAM generated yttria-stabilized zirconia and glass-ceramic laminate veneers.
When feldspathic porcelain (FP) laminate veneers are used to mask tooth discoloration that extends into the dentin, significant tooth reduction is needed to provide space for the opaque layer and optimize the bonding of the restoration. The purpose of this study was to investigate the color effect of trial insertion paste (TP), composite resin abutment (CRA), and veneer regions on the optical properties of feldspathic porcelain (FP), yttria-stabilized zirconia (Y-TZP), and IPS e.max CAD HT (IEC) veneers. A melamine tooth was prepared for a laminate veneer on a model, and a definitive cast was made. The definitive die was scanned by using the TurboDent System (TDS), then 30 CRA were machined and 10 veneers were fabricated for each ceramic material (FP, Y-TZP, IEC). The optical properties of different veneer materials, CRA (A(1), A(2), A(3)) and TP (bleach XL, opaque white, transparent, and yellow) were evaluated in the cervical, body, and incisal regions with a spectrophotometer. Results were analyzed by using 1-way ANOVA (.05). The color difference for all the veneers was affected by TP and CRA colors in different regions. The mean values for the Y-TZP veneer color coordinates (L*: 74 ±0.34, a*: 0.09 ±0.20, and b*: 17.43 ±0.44) were significantly different (P<.001) from those of IEC veneers (L*: 70.15 ±0.23, a*: -0.69 ±0.073, and b*:11.48 ±0.30) and FP veneers (L*: 70.00 ±0.86, a*: - 0.28 ±0.203, and b*: 13.86 ±1.08). There was no difference between IEC for L* and FP. Significant difference was detected (P<.001) in color coordinates among the 3 veneer materials for a* and b*. The TP color affected the color difference for all veneer materials except the Y-TZP, while there was no effect on the CRA color. The magnitude of color coordinates changed as a function of TP color and veneer material.


Neuroendocrinological effects of L-threo-3, 4-dihydroxyphenylserine (DOPS), a putative norepinephrine precursor, on healthy volunteers.
The effect of L-threo-3, 4-dihydroxyphenylserine (DOPS) on plasma cortisol, prolactin, thyrotropin-stimulating hormone (TSH) and growth hormone concentrations was studied in nine healthy male volunteers. The drug was administered orally (300 mg or 600 mg DOPS) using a multiple crossover placebo-controlled study design. Plasma hormone concentrations were measured at 30 minute intervals for 3 hours after dosing. Plasma DOPS peak concentrations were observed between 2 and 3 hours after dosing. DOPS, however, had no effect on plasma hormone concentrations and this may be attributed to the known low brain permeability of DOPS in healthy subjects.


Effects of prenatal propofol exposure on postnatal development in rats.
Preclinical studies suggest that propofol may cause damage to immature neurons. However, the effect of maternal propofol exposure on the neuronal development of the offspring is largely unknown. In this study, pregnant rats were assigned to receive continuous infusion of saline (control) or propofol for 1 h (1HP) or 2 h (2HP) on gestational day 18. An additional group (lipid) was assigned to receive continuous infusion of intralipid fat emulsion (vehicle of propofol) for 2 h. Pups were then tested on the appearance and progression of sensory and physical motor abilities between postnatal day 1 (P1) and P28. The brain and body weights of pups from 2HP group on P10 were significantly lower than those from the saline control group, although they were the same in all four groups at birth (P0). Pups from 1HP and 2HP groups, but not lipid group, showed slower maturation of eyes (delayed opening) and several neurological reflexes (hindlimb reflex, righting reflex); they also showed delayed improvement in execution on gait reflex and inclined board tests. The forelimb reflex and negative geotaxis were also delayed in 2HP group. All parameters examined except body weight of 2HP pups recovered to normal levels by P28. We conclude that administration of propofol to pregnant rats leads to retardation in physical and neurological reflex development in their offspring.


New role of a histone chaperone, HirA: Involvement in kojic acid production associated with culture conditions in Aspergillusoryzae.
Kojic acid (KA) is a representative secondary metabolite of Aspergillus oryzae, but the underlying molecular mechanisms that regulate KA production are unknown. This study tried to find a genetic factor of KA production in A. oryzae, with a special focus on liquid cultures. We screened a gene predicted to encode HirA, a subunit of the histone chaperon, the HIR complex. A gene disruption strain of hirA showed decreased KA production in liquid culture, whereas it showed increased KA production in plate culture. We confirmed that a decrease/increase of KA production observed by hirA disruption was caused by altered expression of kojA and kojR. These observations suggested the regulatory role of histone chaperon in secondary metabolism in filamentous fungi. So far as we know, this report is the first showing that disruption of a gene resulted in the opposite effect on KA production in liquid and plate cultures in A. oryzae.


Lack of persistent effects of ketamine in rodent models of depression.
We investigated the immediate and enduring effects of ketamine in behavioral and neurochemical assays predictive of antidepressant activity. One week after a single administration of ketamine (50-160 mg/kg), otherwise experimentally naive rats and mice were tested either in the forced swim test (FST) or the tail suspension test (TST). Other mice were also tested twice in the FST: immediately and 2 weeks after a single dose (1.25-50 mg/kg) of ketamine. In the next series of experiments, rats treated for 2 weeks twice daily with ketamine (50 or 160 mg/kg) or desipramine (10 mg/kg) were challenged with apomorphine and scored for locomotor activity and assayed for the density of cortical beta-adrenoceptors. The latter test was also carried out in rats that had received a single dose of ketamine (50 mg/kg) 1 week before the assay. The antidepressant-like (FST) and locomotor effects of ketamine (50 mg/kg) and desipramine (10 mg/kg) were assessed after their chronic (2 weeks, twice daily) administration as well. We report the lack of enduring antidepressant-like effect of ketamine in both rats and mice. A 2-week treatment with ketamine neither changed apomorphine-evoked locomotor hyperactivity nor did it decrease the density of cortical beta-adrenoceptors. However, some tolerance to the antidepressant-like effect of ketamine was noted in the FST, but it was accompanied by sensitization to its locomotor stimulatory effects. These data indicate that ketamine neither produces enduring antidepressant-like effects in rodents nor does it display antidepressant-like behavioral or neurochemical effects after chronic treatment.


Long-term results of a phase II trial of high-dose radiotherapy (60 Gy) and UFT/l-leucovorin in patients with non-resectable locally advanced rectal cancer (LARC).
Preoperative radiochemotherapy is a cornerstone in patients with non- resectable locally advanced rectal cancer (LARC). To improve outcome (number of R0 resections and survival) high-dose radiotherapy (RT) was combined with oral UFT/l-leucovorin to allow tumour regression before radical intended surgery. Pelvic RT was delivered with megavoltage photons using a 5 field technique. RT was CT-based, given 5 days a week through one posterior field and two lateral fields (48.6 Gy/27 fractions) to encompass the primary tumour and the regional lymph nodes. In addition, the tumour bed received a concurrent boost (5.4 Gy/27 fractions) and a final boost (6 Gy/3 fractions); thus GTV received 60 Gy/30 fractions. Concurrent with RT patients received a daily dose of oral UFT 300 mg/m(2) plus l-leucovorin 22.5 mg 5/7 days (divided in three doses). From September 2000 to November 2004, 52 patients (median age 60 years (32-83); median PS 0 (0-2)) with LARC (36 primary, 16 recurrent) were included in this phase II study. All but three patients received the planned 60 Gy, median duration of RT was 42 days (25-49). Toxicity was very modest; only four patients had a dose reduction of UFT. No hematological toxicity of clinical significance was seen. Non-hematological toxicity grade 1 (GI-toxicity, fatigue and/or dysuria) was frequently observed but only four patients experienced grade 3 toxicity (diarrhoea and/or nausea/vomiting). Forty patients (77%) were operated (30 R0, 5 R1, 5 R2) median 55 days (27-112) after completion of RT. Seven (13%) patients had a pathological complete response (pCR). Thirty-one patients (60%) died after median 25.4 months (1.6-45.2 months). Twenty-one patients (40%) are still alive June 2007. Preoperative high-dose RT and concomitant UFT produces major regression in most patients with non-resectable LARC and thus a good chance of cure.


A liquid-crystal-based DNA biosensor for pathogen detection.
A liquid-crystal (LC)-filled transmission electron microscopy (TEM) grid cell coated with the cationic surfactant dodecyltrimethylammonium bromide (DTAB), to which a single-stranded deoxyribonucleic acid probe (ssDNAprobe) was adsorbed at the LC/aqueous interface (TEMDTAB/DNA), was applied for the highly specific detection of target DNA molecules. The DTAB-coated E7 (used LC mixture) in the TEM grid (TEMDTAB) exhibited a homeotropic orientation, and changed to a planar orientation upon adsorption of the ssDNAprobe. The TEMDTAB/DNA was then exposed to complementary (target) ssDNA, which resulted in a planar-to-homeotropic configurational change of E7 that could be observed through a polarized optical microscope under crossed polarizers. The optimum adsorption density (2 μM) of ssDNAprobe enabled the detection of ≥0.05 nM complementary ssDNA. This TEMDTAB/DNA biosensor could differentiate complementary ssDNA from mismatched ssDNA as well as double-stranded DNA. It also successfully detected the genomic DNAs of the bacterium Erwinia carotovora and the fungi Rhazictonia solani. Owe to the high specificity, sensitivity, and label-free detection, this biosensor may broaden the applications of LC-based biosensors to pathogen detection.


Early Anesthesia Exposure and the Effect on Visual Acuity, Refractive Error, and Retinal Nerve Fiber Layer Thickness of Young Adults.
To investigate whether being anesthesia administered at least once in early life influenced 3 main proxies of visual function: visual acuity, refractive error, and optic nerve health in young adulthood. At age 20 years, participants of the Western Australian Pregnancy Cohort Study had comprehensive ocular examinations including visual acuity, postcycloplegic refraction, and multiple scans of the optic disc. We identified individuals who had at least 1 procedure requiring anesthesia during the first 3 years of life (between 1990 and 1994) and compared their visual outcomes with nonexposed individuals. We excluded 40 participants with strabismus or other ophthalmic disease or surgery and 136 with non-European background. Of 834 participants, 15.2% (n = 127) were exposed to anesthesia at least once before age 3 years. In both exposed and nonexposed groups, median visual acuity (measured using the logarithm of the minimum angle of resolution [LogMAR] chart) was -0.06 LogMAR in the right eye and -0.08 LogMAR in the left eye (P > .05). Median spherical equivalent refractive error was +0.44 diopters (IQR -0.25, +0.63) and +0.31 diopters (IQR -0.38, +0.63) in the exposed and nonexposed group, respectively (P = .126). No difference was detected in mean global retinal nerve fiber layer thickness of the 2 groups (100.7 vs 100.1 μm, P = .830). We were unable to demonstrate an association of exposure to anesthesia as a child with reduced visual acuity or increased myopia or thinning of retinal nerve fiber layer. These findings support the view that anesthesia is unlikely to impair visual development, but further work is needed to establish whether more subtle defects are present and repeated exposures have any effects.


Genotypic variations in photosynthetic and physiological adjustment to potassium deficiency in cotton (Gossypium hirsutum).
A hydroponic culture experiment was conducted to determine genotypic variation in photosynthetic rate and the associated physiological changes in response to potassium (K) deficiency in cotton (Gossypium hirsutum L.) seedlings with contrasting two cotton cultivars in K efficiency. The K-efficient Liaomian18 produced 66.7% more biomass than the K-inefficient NuCOTN99(B) under K deficiency, despite their similar biomass under K sufficiency. Compared with NuCOTN99(B), Liaomian18 showed 19.4% higher net photosynthetic rate (P(n), per unit leaf area) under K deficient solutions and this was associated with higher photochemical efficiency and faster export of soluble sugars from the phloem. The lower net P(n) of NuCOTN99(B) was attributed to higher capacity for nitrate assimilation and lower export of soluble sugars. Furthermore, NuCOTN99(B) showed 38.4% greater ETR/P(n) than Liaomian18 under K deficiency, indicating that more electrons were driven to other sinks. Higher superoxide dismutase (SOD) and lower catalase (CAT) and ascorbate peroxidase (APX) activities resulted in higher levels of reactive oxygen species (ROS; e.g. O(2)(-)and H(2)O(2)) in NuCOTN99(B) relative to Liaomian18. Thus, the K inefficiency of NuCOTN99(B), indicated by lower biomass and net P(n) under K deficiency, was associated with excessively high nitrogen assimilation, lower export of carbon assimilates, and greater ROS accumulation in the leaf.


The SIRT1 activator SRT2104 promotes BMP9-induced osteogenic and angiogenic differentiation in mesenchymal stem cells.
Bone defects resulting from trauma, bone tumors, infections and skeletal abnormalities are a common osteoporotic condition with respect to clinical treatment. Of the known bone morphogenetic proteins (BMPs), BMP9 has the strongest osteogenic differentiation potential, which could be beneficial in the construction of tissue-engineered bone. Silent mating type information regulator 2 homolog-1 (SIRT1) is a highly conserved nicotinamide adenine dinucleotide-dependent deacetylase that deacetylates and modulates histone or non-histone substrates. However, the role of SIRT1 in BMP9-induced osteogenic differentiation of stem cells has not been studied. Furthermore, it is unclear whether SIRT1 interacts with the BMP/Smad and BMP/MAPK pathways in stem cells. We found that SIRT1 expression decreased gradually in a time-dependent manner during BMP9-induced osteogenic differentiation of MSCs. Interactions between SIRT1 and Smad7 promoted degradation of Smad7 and increased Smad1/5/8 phosphorylation. SRT2104, an activator of SIRT, enhanced the expression of osteogenic- and angiogenic-related proteins in BMP9-induced MSCs. In addition, we found that activation of the BMP/MAPK pathway led to osteogenic and angiogenic differentiation of MSCs. Our study demonstrated that SIRT1 expression decreased during BMP9-induced differentiation. The SIRT1 activator SRT2104 promoted BMP9-induced osteogenic and angiogenic differentiation of MSCs through the BMP/Smad and BMP/MAPK signaling pathways.


Bacterial CRISPR: accomplishments and prospects.
In this review we briefly describe the development of CRISPR tools for genome editing and control of transcription in bacteria. We focus on the Type II CRISPR/Cas9 system, provide specific examples for use of the system, and highlight the advantages and disadvantages of CRISPR versus other techniques. We suggest potential strategies for combining CRISPR tools with high-throughput approaches to elucidate gene function in bacteria.


Conduction along the articular branch of the suprascapular nerve.
The maximum sensory conduction velocity was measured along the articular branch of the suprascapular nerve. The potential was evoked by stimulating in the perception area of the nerve above the glenohumeral joint and recorded by an electrode near the suprascapular nerve in the supraclavicular fossa. The maximum conduction velocity averaged 42 m/s, SD 4.6 m/s (20 normal subjects); it decreased slightly with age. When correcting for the error in distance arising from the measurement by obstetric calipers (20%), the maximum conduction velocity averaged 50 m/s. The peak-to-peak amplitude of the main component of the sensory potential was 0.8 muV, SD 0.5 muV. In one of seven patients with a pain syndrome in the shoulder secondary to a brachial plexus neuropathy the velocity and the amplitude of the sensory potential was diminished. In five other patients with pain in the region of the shoulder the conduction velocity was normal but the amplitude was diminished.


SIX1: A Prognostic Biomarker in Uterine Corpus Endometrial Carcinoma.
Uterine Corpus Endometrial Carcinoma (UCEC) is a common malignancy of the female genital tract. The sine oculis homeobox homolog 1 (SIX1) protein has been documented to be important for tumor progression. However, little is known about the relationship between SIX1 and the pathogenesis of UCEC. This study aimed to assess the prognostic value of biomarker SIX1 in UCEC by analyzing clinical traits, immune infiltration, and gene set enrichment analysis. The Wilcoxon signed-rank test and logistic regression were used to analyze the relationship between clinicopathological characteristics and SIX1. The Kaplan-Meier method was used to assess the relationship between clinicopathological characteristics and prognosis verified by immunohistochemistry (IHC). Then gene set enrichment analysis (GSEA) was performed to explore signaling pathways correlated with SIX1 expression in UCEC. Finally, the TIMER2 database was used to analyze the correlation between SIX1 and immune infiltration, and the effect of SIX1 expression on immune cells was calculated with the CIBERSORT algorithm. We found that the expression of SIX1 in UCEC was up-regulated and correlated with a poor prognosis. Analysis showed that the expression of SIX1 was related to various clinical features and was an independent prognostic factor of UCEC. Enrichment analysis showed that SIX1 promoted the occurrence and development of UCEC by regulating multiple signaling pathways. The results of immune infiltration analysis showed that SIX1 has a complex correlation with immune infiltration. Our findings indicate that SIX1 is a promising biomarker for predicting the prognosis of UCEC and is a potential therapeutic target.


Autophagy and Immune-Related Diseases.
Autophagy is an intracellular degradation and recycling machinery by which cellular materials are delivered to the lysosome for disposal. Beyond lysosomal degradation, autophagy genes play additional roles in secretion and membrane-trafficking pathways. Ranging from cell-intrinsic and cell-type-specific regulation of innate inflammatory signaling pathways to intercellular cross talk through secretion of soluble factors (e.g., shaping the MHC immunopeptidome for T cell response, etc.), autophagy exerts multiple functions in driving inflammation and modulating the pathological progression of immune-related disorders such as neurodegenerative diseases, inflammatory bowel diseases, autoimmunity, and metabolic diseases. Notably, owing to the complexity of autophagy process involving multiple proteins and stepwise assembly of protein complexes, noncanonical forms of autophagy or autophagic proteins, which function beyond autophagy, are equally important in the maintenance of cellular homeostasis and pathogenesis. This chapter summarizes the most up-to-date findings of autophagy proteins in the regulation of immune-related diseases. Understanding of the autophagy machinery offers therapeutic strategies for treating inflammatory diseases.


Structural polymorphism of hydrated ether-linked dimyristyl maltoside and melibioside.
The structural polymorphism of two selected disaccharide glycolipids with a maltose (DMMA) and a melibiose (DMME) carbohydrate headgroup linked to dimyristyl alkyl chains were investigated by FTIR-spectroscopy, differential scanning calorimetry (DSC), small-angle X-ray scattering (SAXS) and film-balance measurements. The compounds displayed thermotropic multilamellar phases. In the gel phase, DMMA formed also a crystalline phase of orthorhombic symmetry, and DMME an interdigitated phase. The gel to liquid crystalline phase transition temperature T(c) of DMMA depended on the storage and hydration conditions, a precooled sample having a T(c) around 45 degrees C, and a freshly prepared sample around 33 degrees C. In contrast, the phase transition temperature for the gel to liquid crystalline phase of DMME was always found at 24 degrees C. Surface pressure isotherms of the lipids on water and buffer showed that DMMA covers only a small surface area (approximately 35A(2)) whereas DMME requires 50 A(2) of space on the surface. Films of DMMA can be compressed up to a maximum compressibility Pi(max) of 54 mN m(-1) whereas the tilted DMME forms less stable films with Pi(max) of 34 mN m(-1). These different structural characteristics reflect the different conformations of the disaccharide head groups. The presence of the alpha1-->4 linked maltose head group in DMMA and an alpha1-->6 linked melibiose head group in DMME induces geometrical structures ranging from a slightly wedge-shaped towards a more tilted structure, and as a consequence of Israelachvilis packing model, to the formation of different phases. In addition, the structural constraints of DMME allow the formation of a phase with interdigitated hydrocarbon chains.


Use of iso-osmolar nonionic dimeric contrast media in multidetector row computed tomography angiography for patients with renal impairment.
We wanted to determine the rate of contrast-induced nephropathy (CIN) caused in patients with renal impairment undergoing multidetector row computed tomography (MDCT) angiography with intravenous administration of iso-osmolar dimeric contrast media (iodixanol). The first consecutive 100 patients referred to CT with a serum creatinine level (SCr) between 1.5 and 6 mg/dL were enrolled in the study. Serum creatinine also was determined on days 3 and 7 after the intravenous administration of 100 mL of iodixanol 270 with 5 mL/s. A CIN was considered if variation of SCr on day 3 was >0.5 mg/dl above baseline. Nine patients developed a CIN after MDCT angiography; 7 of them recovered completely by day 7, and the remaining 2 showed elevated SCr on day 7 but did not develop renal failure during their hospital stay. MDCT angiography performed in patients with impaired renal function with iodixanol may result in CIN but complete recovery is probable.


Diagnosis of Patients with Acute Dizziness.
Using an algorithmic approach to acutely dizzy patients, physicians can often confidently make a specific diagnosis that leads to correct treatment and should reduce the misdiagnosis of cerebrovascular events. Emergency clinicians should try to become familiar with an approach that exploits timing and triggers as well as some basic "rules" of nystagmus. The gait should always be tested in all patients who might be discharged. Computed tomographic scans are unreliable to exclude posterior circulation stroke presenting as dizziness, and early MRI (within the first 72 hours) also misses 10% to 20% of these cases.


Evaluation of electrospray differential mobility analysis for virus particle analysis: Potential applications for biomanufacturing.
The technique of electrospray differential mobility analysis (ES-DMA) was examined as a potential potency assay for routine virus particle analysis in biomanufacturing environments (e.g., evaluation of vaccines and gene delivery products for lot release) in the context of the International Committee of Harmonisation (ICH) Q2 guidelines. ES-DMA is a rapid particle sizing method capable of characterizing certain aspects of the structure (such as capsid proteins) and obtaining complete size distributions of viruses and virus-like particles. It was shown that ES-DMA can distinguish intact virus particles from degraded particles and measure the concentration of virus particles when calibrated with nanoparticles of known concentration. The technique has a measurement uncertainty of ≈20%, is linear over nearly 3 orders of magnitude, and has a lower limit of detection of ≈10(9)particles/mL. This quantitative assay was demonstrated for non-enveloped viruses. It is expected that ES-DMA will be a useful method for applications involving production and quality control of vaccines and gene therapy vectors for human use.


The transcription factor OsbHLH035 mediates seed germination and enables seedling recovery from salt stress through ABA-dependent and ABA-independent pathways, respectively.
Many transcription factors (TFs), such as those in the basic helix-loop-helix (bHLH) family, are important for regulating plant growth and plant responses to abiotic stress. The expression of OsbHLH035 is induced by drought and salinity. However, its functional role in rice growth, development, and the salt response is still unknown. The bHLH TF OsbHLH035 is a salt-induced gene that is primarily expressed in germinating seeds and seedlings. Stable expression of GFP-fused OsbHLH035 in rice transgenic plants revealed that this protein is predominantly localized to the nucleus. Osbhlh035 mutants show delayed seed germination, particularly under salt-stress conditions. In parallel, abscisic acid (ABA) contents are over-accumulated, and the expression of the ABA biosynthetic genes OsABA2 and OsAAO3 is upregulated; furthermore, compared with that in wild-type (WT) seedlings, the salt-induced expression of OsABA8ox1, an ABA catabolic gene, in germinating Osbhlh035 mutant seeds is downregulated. Moreover, Osbhlh035 mutant seedlings are unable to recover from salt-stress treatment. Consistently, sodium is over-accumulated in aerial tissues but slightly reduced in terrestrial tissues from Osbhlh035 seedlings after salt treatment. Additionally, the expression of the sodium transporters OsHKT1;3 and 1;5 is reduced in Osbhlh035 aerial and terrestrial tissues, respectively. Furthermore, genetic complementation can restore both the delayed seed germination and the impaired recovery of salt-treated Osbhlh035 seedlings to normal growth. OsbHLH035 mediates seed germination and seedling recovery after salt stress relief through the ABA-dependent and ABA-independent activation of OsHKT pathways, respectively.


Formation of glomerulus-like structures by the olfactory nerve neonatal bulbectomy.
Evidence presented here suggests that glomerulus formation within the olfactory bulb of the rat, which is mostly a postnatal event, is directed by the olfactory nerve rather than by the influences of mitral and tufted cells.


Pituitary adenomas associated with elevated blood follicle-stimulating hormone levels: a histologic, immunocytologic, and electron microscopic study of two cases.
The histologic, immunocytologic, and electron microscopic features of pituitary adenomas surgically removed from two men with elevated levels of blood follicle-stimulating hormone (FSH) are described. In both cases, the high blood FSH levels were reduced after surgery. By light microscopy, the tumors corresponded to chromophobic adenomas, and the immunoperoxidase technique revealed the presence of immunoreactive FSH (beta-subunit) in the cytoplasm of the adenoma cells. By electron microscopy, the adenoma cells differed considerably from nontumorous FSH cells. They were smaller and angular and contained numerous microtubules as well as spherical secretory granules measuring 100 to 250 nm in diameter and often lining up along the cell membranes. The present findings are consistent with the view that FSH-producing adenomas may originate in the human pituitary.


Synthesis and in vitro cytotoxicity of C(20)(RS)-camptothecin analogues modified at both B (or A) and E ring.
A series of C(7) and C(20)-substituted camptothecin derivatives (12-14, 16-18) are prepared. Their syntheses and in vitro cytotoxicities are reported.


SARS-Cov-2 infection and neuropathological findings: a report of 18 cases and review of the literature.
COVID-19-infected patients harbour neurological symptoms such as stroke and anosmia, leading to the hypothesis that there is direct invasion of the central nervous system (CNS) by SARS-CoV-2. Several studies have reported the neuropathological examination of brain samples from patients who died from COVID-19. However, there is still sparse evidence of virus replication in the human brain, suggesting that neurologic symptoms could be related to mechanisms other than CNS infection by the virus. Our objective was to provide an extensive review of the literature on the neuropathological findings of postmortem brain samples from patients who died from COVID-19 and to report our own experience with 18 postmortem brain samples. We used microscopic examination, immunohistochemistry (using two different antibodies) and PCR-based techniques to describe the neuropathological findings and the presence of SARS-CoV-2 virus in postmortem brain samples. For comparison, similar techniques (IHC and PCR) were applied to the lung tissue samples for each patient from our cohort. The systematic literature review was conducted from the beginning of the pandemic in 2019 until June 1st, 2022. In our cohort, the most common neuropathological findings were perivascular haemosiderin-laden macrophages and hypoxic-ischaemic changes in neurons, which were found in all cases (n = 18). Only one brain tissue sample harboured SARS-CoV-2 viral spike and nucleocapsid protein expression, while all brain cases harboured SARS-CoV-2 RNA positivity by PCR. A colocalization immunohistochemistry study revealed that SARS-CoV-2 antigens could be located in brain perivascular macrophages. The literature review highlighted that the most frequent neuropathological findings were ischaemic and haemorrhagic lesions, including hypoxic/ischaemic alterations. However, few studies have confirmed the presence of SARS-CoV-2 antigens in brain tissue samples. This study highlighted the lack of specific neuropathological alterations in COVID-19-infected patients. There is still no evidence of neurotropism for SARS-CoV-2 in our cohort or in the literature.


Clinical evaluation strategies for a live attenuated tetravalent dengue vaccine.
Butantan Institute is a public Brazilian biomedical research-manufacturer center affiliated to the São Paulo State Secretary of Health. Currently, Butantan is one of the main public producers of vaccines, antivenoms, and antitoxins in Latin America. The partnership between Butantan and the National Institutes of Health (NIH) of the United Sates has been one of the longest and most successful partnerships in the development and manufacturing of new vaccines. Recently, Butantan Institute has developed and manufactured a lyophilized tetravalent live attenuated dengue vaccine with the four dengue viruses attenuated and licensed from the Laboratory of Infectious Diseases at The National Institutes of Allergy and Infectious Diseases (LID/NIAID/NIH). The objective of this paper is to describe the clinical evaluation strategies of a live attenuated tetravalent dengue vaccine (Butantan-DV) developed and manufactured by Butantan Institute. These clinical strategies will be used to evaluate the Butantan-DV Phase III trial to support the Butantan-DV licensure for protection against any symptomatic dengue caused by any serotype in people aged 2 to 59 years.


Right ventricular thrombosis in two patients with pulmonary atresia with intact ventricular septum.
Thrombosis was detected in the right ventricle 7 days after a bidirectional Glenn operation in a 1-year-old boy with pulmonary atresia with intact ventricular septum (PAIVS) and immediately before pulmonary valvuloplasty in a 21-day-old boy with PAIVS. The risk of thrombosis and the blood clotting cascade should be assessed by blood tests, and surveillance echocardiography should be frequently applied in order to diagnose thrombosis early in such patients.


Alterations in cognitive outcome between 3 and 12 months in survivors of out-of-hospital cardiac arrest.
To prospectively investigate cognitive recovery from 3 to 12 months after resuscitation from out-of-hospital cardiac arrest (OHCA) and the associations between cognitive performance at 3 months and health-related quality of life (HRQL), psychological distress and work status after 12 months. At both assessments, neuropsychological tests were used to measure aspects of general mental ability, verbal and visual memory, psychomotor speed and executive function. The Short Form-36 (SF-36) was used to measure mental and physical HRQL, and the Hospital Anxiety and Depression Scale (HADS) to assess psychological distress. 33 survivors completed both exams (31 males, mean age 58.6 years, SD=13). The OHCAs were witnessed and due to cardiac origins. Nine patients were awake at admission to the hospital. Longer coma duration was associated with poorer cognitive results. Memory impairments were the most common symptom. The mean changes and effect sizes indicated minor improvements in cognitive performance from 3 to 12 months (Hedges g≤.26). Reliable change indices for an individual's results further confirmed the stability of the group statistics. The HADS scores showed increased depressive symptoms, and mental HRQL was reduced from 3 to 12 months. Higher reports of psychological distress were related to worse HRQL. Work participation increased. Better cognitive results at 3 months were correlated with better HRQL and return to work at 12 months. The current data describe stability in results from 3 to 12 months. A worse cognitive performance at 3 months and higher reports of psychological distress were associated with lower HRQL.


Risk of relapse and death from colorectal cancer and its related factors using non-Markovian Multi-State model.
This study aimed at modeling the risk of local relapse and death from colorectal cancer after the first treatment and its related factors using multi-state models. In cancer studies modeling the course of disease regarding events which happen to patients is of great importance. By considering death as the final endpoint while incorporating the intermediate events, multi-state models have been developed. This was a historical cohort study in which 235 patients with colorectal cancer, who referred to Omid Hospital in Mashhad between 2006 and 2011, were studied and followed up until 2017. The transition probabilities to death due to metastasis with or without experiencing local relapse and variables related to them were determined using the non-Markovian multi-state model in three states of disease, local relapse and death. The probability of not experiencing either of the events, just relapse and death in the first 5 years were 0.45, 0.09 and 0.46 respectively. If patients did not experience any event in the first year of treatment, the probability of relapse and death before the fifth year were 0.04 and 0.33 respectively and if they did experience relapse during this time, the probability of death by the fifth year was 0.62. The stage of cancer was associated with relapse and death, while ethnicity and history of addiction were related to death without relapse and BMI had a significant relationship with death after relapse (p<0.05). Risk of death in patients with colorectal cancer depends on local relapse and the time between them.


Protection provided by cyclosporin A against excitotoxic neuronal death is genotype dependent.
Previous studies have shown that the immunosuppressant cyclosporin A (CsA), a specific blocker of the mitochondrial permeability transition (MPT) pore, can dramatically ameliorate the selective neuronal necrosis resulting from ischemia-reperfusion, traumatic brain injury, and N-methyl-d-aspartate (NMDA)-evoked neurotoxicity. The purpose of this study was to determine whether two different immunosuppressants, CsA and FK-506, could ameliorate the neuronal damage observed after kainate-induced seizures in strains that are differentially susceptible to excitotoxin-induced cell death. Excitotoxin-resistant (C57BL/6) or -susceptible (FVB/N) mice were administered kainate alone (30 mg/kg), CsA alone (5, 10, or 20 mg/kg), or one of the immunosuppressants (CsA, 5 mg/kg or 10 mg/kg; FK-506, 0.5 mg/kg) followed by kainate. After drug administration, mice were monitored continuously for the onset and extent of seizure activity. After a survival of 7 days, animals were assessed for hippocampal damage. Whereas CsA alone induced no epileptogenic effects and both immunosuppressants were without effect on the induction of kainate-induced seizures, administration of CsA to excitotoxin-susceptible mice (FVB/N) virtually eliminated neuronal cell death. In contrast, induction of neuronal cell death was evident when CsA was administered to excitotoxin-resistant mice (C57BL/6). Administration of FK-506, another commonly used immunosuppressant, which lacks an effect on the MPT, had no effect on modification of susceptibility to kainate-induced cell death in either strain. As our data show differential protection of hippocampal neurons against excitotoxic cell death by pretreatment with CsA, these results suggest that strain-dependent differences in mitochondrial integrity and function may exist.


The Dual Roles of NRF2 in Cancer.
NRF2 has been traditionally considered as a tumor suppressor because its cytoprotective functions are deemed to be the main cellular defense mechanism against exogenous and endogenous insults, including xenobiotics and oxidative stress. However, several recent studies demonstrate that hyperactivation of the NRF2 pathway creates an environment that favors the survival of normal as well as malignant cells, protecting them against oxidative stress, chemotherapeutic agents, and radiotherapy. In a rapidly advancing field, this review summarizes some of the known mechanisms by which NRF2 can exert its oncogenic functions, and describes the current status of NRF2 inhibitors, providing a clear rationale for the consideration of NRF2 as a powerful putative therapeutic target in cancer treatment.


Prognostic Factors in Trauma Patients Transported by Physician-Staffed Helicopter in Japan: An Investigation Based on the Japan Trauma Data Bank.
We retrospectively investigated prognostic factors for patients evacuated by the physician-staffed helicopter emergency medical service using the Japan Trauma Data Bank. The study period was from January 2004 to May 2019. The subjects were divided into 2 groups according to the outcome: the survival group and the fatal group. A total of 19,370 patients were enrolled as subjects. There were 17,080 patients in the survival group and 2,290 in the fatal group. In a multivariate analysis of factors that showed statistical significance in a univariate analysis, the Revised Trauma Score, age, Injury Severity Score, Maximum Abbreviated Injury Scale (MAX-AIS) for the upper extremity (negative), year of helicopter dispatch, Japan Coma Scale, MAX-AIS for the head, MAX-AIS for the abdomen/pelvis, and MAX-AIS for the spine were identified as significant predictors of a fatal outcome . This is the first report to investigate the prognostic factors of patients evacuated by helicopter emergency medical service using the Japan Trauma Data Bank. The results suggest that physiological abnormality, age, traumatic anatomic abnormality (other than upper extremity abnormality), and year of helicopter dispatch may be prognostic factors.


Meat consumption and cancer of the large bowel.
Since the major reviews on diet and cancer by the World Cancer Research Fund (WCRF) and by the British Department of Health's Committee on Medical Aspects of Food Policy (COMA) in 1997 and 1998, additional epidemiological studies relating (red) meat consumption and colorectal cancer have been published or found by search. These are collected here. Thirty adequate case-control studies have been published up to 1999 (from 16 different countries). Twenty of them found no significant association of (red) meat with colorectal cancer. Of the remaining 10 studies reporting an association, some obtained statistical significance only in rectal or colon cancers, another only in men, not women, or found a stronger association with pasta and rice, or used an inadequate food list in the food frequency questionnaire. Fifteen cohort studies have now been published. Only in three were significant associations of (red) meat found with colorectal cancer. Two of these positive studies were from the same group in the USA (relative risk 1.7). The results of the third positive study appear to conflict with data from part of the vegetarians follow up mortality study. Here, five groups of vegetarians (in three different countries) with socially matched controls were followed up (total 76 000 people). Mortality from colorectal cancer was not distinguishable between vegetarians and controls. While it is still possible that certain processed meats or sausages (with a variety of added ingredients) or meats cooked at very high temperature carry some risk, the relationship between meats in general and colorectal cancer now looks weaker than the 'probable' status it was judged to have by the WCRF in 1997.


Coupling of Cu(100) and (110) Facets Promotes Carbon Dioxide Conversion to Hydrocarbons and Alcohols.
Copper can efficiently electro-catalyze carbon dioxide reduction to C2+ products (C2 H4 , C2 H5 OH, n-propanol). However, the correlation between the activity and active sites remains ambiguous, impeding further improvements in their performance. The facet effect of copper crystals to promote CO adsorption and C-C coupling and consequently yield a superior selectivity for C2+ products is described. We achieve a high Faradaic efficiency (FE) of 87 % and a large partial current density of 217 mA cm-2 toward C2+ products on Cu(OH)2 -D at only -0.54 V versus the reversible hydrogen electrode in a flow-cell electrolyzer. With further coupled to a Si solar cell, record-high solar conversion efficiencies of 4.47 % and 6.4 % are achieved for C2 H4 and C2+ products, respectively. This study provides an in-depth understanding of the selective formation of C2+ products on Cu and paves the way for the practical application of electrocatalytic or solar-driven CO2 reduction.


Effect of a gentle Iyengar yoga program on gait in the elderly: an exploratory study.
To determine if a tailored yoga program could improve age-related changes in hip extension, stride length, and associated indices of gait function in healthy elders, changes that have been linked to increased risk for falls, dependency, and mortality in geriatric populations. Single group pre-post test exploratory study. A 3-dimensional quantitative gait evaluation, including kinematic and kinetic measurements, was performed pre- and postintervention. Changes over time (baseline to postintervention) in primary and secondary outcome variables were assessed using repeated-measures analysis of variance. Yoga exercises were performed in an academic medical center (group classes) and in the subjects' homes (yoga home-practice assignments). Pre- and postassessments were performed in a gait laboratory. Twenty-three healthy adults (age range, 62-83 y) who were naive to yoga were recruited; 19 participants completed the program. An 8-week Iyengar Hatha yoga program specifically tailored to elderly persons and designed to improve lower-body strength and flexibility. Participants attended two 90-minute yoga classes per week, and were asked to complete at least 20 minutes of directed home practice on alternate days. Peak hip extension, average anterior pelvic tilt, and stride length at comfortable walking speed. Peak hip extension and stride length significantly increased (F1,18=15.44, P<.001; F1,18=5.57, P=.03, respectively). We also observed a trend toward reduced average pelvic tilt (F1,18=4.10, P=.06); adjusting for the modifying influence of frequency of home yoga practice strengthened the significance of this association (adjusted F1,17=14.30, P=.001). Both the frequency and duration of yoga home practice showed a strong, linear, dose-response relationship to changes in hip extension and average pelvic tilt. Findings of this exploratory study suggest that yoga practice may improve hip extension, increase stride length, and decrease anterior pelvic tilt in healthy elders, and that yoga programs tailored to elderly adults may offer a cost-effective means of preventing or reducing age-related changes in these indices of gait function.


Anti-Inflammatory Effects of Hyptis albida Chloroform Extract on Lipopolysaccharide-Stimulated Peritoneal Macrophages.
We examined the effects of a chloroform extract of Hyptis albida (CHA) on inflammatory responses in mouse lipopolysaccharide (LPS) induced peritoneal macrophages. Our findings indicate that CHA inhibits LPS-induced production of tumor necrosis factor (TNF- α ) and interleukin-6 (IL-6). During the process, levels of cyclooxygenase-2 (COX-2), nitric oxide synthase (iNOS), and nitric oxide (NO) increased in the mouse peritoneal macrophages; however, the extract suppressed them significantly. These results provide novel insights into the anti-inflammatory actions of CHA and support its potential use in the treatment of inflammatory diseases.


Three-Dimensional Ultrasound of Carotid Plaque.
Measurement of plaque burden is different from measurement of carotid intima-media thickness (IMT). Carotid total plaque area is a stronger predictor of cardiovascular risk than IMT, and in contrast to progression of IMT, which does not predict cardiovascular events, progression of total plaque area and total plaque volume strongly predict cardiovascular events. Measurement of plaque burden is useful in genetic research, and in evaluation of new therapies for atherosclerosis. Perhaps more importantly, it can be used for management of patients. A strategy called "treating arteries instead of treating risk factors" markedly reduces risk among patients with asymptomatic carotid stenosis.


Biomechanical study on the stability and strain conduction of intertrochanteric fracture fixed with proximal femoral nail antirotation versus triangular supporting intramedullary nail.
Based on the features of the three-dimensional spatial structure of the proximal femoral trabeculae, we developed a bionic triangular supporting intramedullary nail (TSIN) for the treatment of the femoral intertrochanteric fracture. The current study aimed to compare the mechanical stability and restoration of mechanical conduction between proximal femoral nail antirotation (PFNA) and TSIN to fix the intertrochanteric fractures. Firstly, five sets of PFNA and TSIN with the same size were selected and fixed on a biomechanical testing machine, and strain gauges were pasted on the main nail, lag screw, and supporting screw to load to the vertical load to 600 N, and the displacement and strain values were recorded. Secondly, formalin-preserved femurs were selected, and the left and right femurs of the same cadaver were randomly divided into two groups to prepare intertrochanteric femur fractures (AO classification 31-A1), which were fixed with PFNA (n = 15) and TSIN (n = 15), respectively. Sixteen sites around the fracture line were chosen to paste strain gauges and loaded vertically to 600 N, and then, the fracture fragment displacement and strain values were recorded. Finally, a 10,000-cycle test ranging from 10 to 600 N was conducted, and the cycle number and displacement value were recorded. The overall displacement of PFNA was 2.17 ± 0.18 mm, which was significantly greater than the displacement of the TSIN group (1.66 ± 0.05 mm, P < 0.05) under a vertical load of 600 N. The strain below the PFNA lag screw was 868.29 ± 147.85, which was significantly greater than that of the TSIN (456.02 ± 35.06, P < 0.05); the strain value at the medial side of the PFNA nail was 444.00 ± 34.23, which was significantly less than that of the TSIN (613.57 ± 108.00, P < 0.05). Under the vertical load of 600 N, the displacement of the fracture fragments of the PFNA group was 0.95 ± 0.25 mm, which was significantly greater than that of the TSIN group (0.41 ± 0.09 mm, P < 0.05). The femoral specimens in the PFNA group showed significantly greater strains at the anterior (1, 2, and 4), lateral (7, 9, and 10), posterior (11), and medial (15 and 16) sites than those in the TSIN group (all P < 0.05). In the cyclic compression experiment, the displacements of the PFNA group at 2000, 4000, 6000, 8000, and 10,000 cycles were 1.38 mm, 1.81 mm, 2.07 mm, 2.64 mm, and 3.58 mm, respectively, which were greater than the corresponding displacements of the TSIN group: 1.01 mm, 1.48 mm, 1.82 mm, 2.05 mm, and 2.66 mm (P8000 = 0.012, P10000 = 0.006). The current study showed that TSIN had apparent advantages in stability and stress conduction. TSIN enhanced the stability of intertrochanteric fractures, particularly in superior fracture fragments, improved stress conduction, reduced the stress in the anterior and medial femur, and restored the biomechanical properties of the femur.


Radial anatomic variation of ultrasonic velocity in human cortical bone.
Quantitative ultrasound techniques can be used to retrieve cortical bone quality. The aim of this study was to investigate the anatomic variations in speed of sound (SOS) in the radial direction of cortical bone tissue. SOS measurements were realized in 17 human cortical bone samples with a 3.5-MHz transverse transmission device. The radial dependence of SOS was investigated in a direction perpendicular to the periosteum. For each sample, bone porosity was measured using an X-ray micro-computed tomography device. The mean SOS was 3586 ± 255 m/s. For 16 of 17 specimens, similar radial variations in SOS were observed. In the periosteal region, SOS first decreased in the direction of the endosteum and reached a minimum value approximately in the middle of the cortical bone. SOS then increased, moving to the endosteal region. A significant negative correlation was obtained between SOS and porosity (R = -0.54, p = 0.02).


Aboriginal and/or Torres Strait Islander women's body image: A qualitative study.
Aboriginal and/or Torres Strait Islander peoples refer to the traditional owners of Australia and have the oldest continuing culture in the world. Body image has scarcely been investigated among adult Aboriginal and/or Torres Strait Islander (Indigenous) women, despite evidence that racism and colourism broadly contribute to adverse psychological outcomes for this population. Therefore, we conducted a qualitative study investigating Indigenous womens' body image with specific focus on racism, colourism, and cultural identity. Sixteen Indigenous women completed individual interviews or took part in group yarns - a culturally sanctioned method of information sharing. A reflexive thematic analysis generated three themes: (i) Dominant beauty ideals in Australia exclude Indigenous women and are informed by colonisation and stereotypes of what Indigenous women "should" look like, (ii) Variations in Indigenous women's identities and appearances influences the types of discrimination that they receive and impacts their sense of belonging, and (iii) A change journey occurs over time towards body acceptance which is informed by changes in understandings of body image and cultural identity. Broadly, participants described racism and colourism as negatively impacting their body image. Importantly, developing a strong cultural identity mitigated these impacts by facilitating both a sense of belonging and body acceptance - highlighting a potential protective factor.


Diversity, functional potential, and assembly of bacterial communities in metal(loid)-contaminated sediments from a coastal industrial basin.
A comprehensive understanding of ecological processes related to bacterial communities in these ecosystems is critical for improving the sustainability of estuarine-coastal ecosystem functions. However, the community composition, functional potential, and assembly mechanisms of bacterial community in metal(loid)-contaminated estuarine-coastal habitats remain poorly understood, especially along lotic systems extending from rivers to estuaries and to bays. Here, we collected sediment samples associated with sewage outlets from rivers (upstream/midstream of sewage outlet), estuaries (sewage outlets), and Jinzhou Bay (downstream of sewage outlets) within Liaoning Province, China in order to evaluate the relationships between microbiome and metal(loid) contamination. Sewage discharge markedly increased the concentrations of metal(loid)s in sediments, including of As, Fe, Co, Pb, Cd, and Zn. Significant discrepancies in alpha diversity and community composition were observed among the sampling sites. The above dynamics were primarily caused by salinity and metal(loid) concentrations (i.e., of As, Zn, Cd, and Pb). Furthermore, metal(loid) stress significantly increased abundances of metal(loid)-resistant genes, but decreased abundances of denitrification genes. Dechloromonas, Hydrogenophaga, Thiobacillus, and Leptothrix were denitrifying bacteria present within sediments of this estuarine-coastal ecosystem. Moreover, the stochastic processes dominated the community assembly in estuary offshore sites, while deterministic processes dominated river community assembly mechanisms. Salinity and total nitrogen concentration, rather than metal(loid) concentrations, governed the assembly processes in these sites. Overall, these elucidate mechanisms involved in constructing community diversities, functional potential, and assembly.


Functional characterization of transcription factor binding sites for HNF1-alpha, HNF3-beta (FOXA2), HNF4-alpha, Sp1 and Sp3 in the human prothrombin gene enhancer.
Prothrombin is a key component in blood coagulation. Overexpression of prothrombin leads to an increased risk of venous thrombosis. Therefore, the study of the transcriptional regulation of the prothrombin gene may help to identify mechanisms of overexpression. The aim of our study was to localize the regions within the prothrombin enhancer responsible for its activity, to identify the proteins binding to these regions, and to establish their functional importance. We constructed a set of prothrombin promoter 5' deletion constructs containing the firefly luciferase reporter gene, which were transiently transfected in HepG2, HuH7 and HeLa cells. Putative transcription factor (TF) binding sites were evaluated by electrophoretic mobility shift assays. The functional importance of each TF binding site was evaluated by site directed mutagenesis and transient transfection of the mutant constructs. We confirmed the major contribution of the enhancer region to the transcriptional activity of the prothrombin promoter. Analysis of this region revealed putative binding sites for hepatocyte nuclear factor HNF4, HNF3-beta and specificity protein(Sp)1. We identified six different TFs binding to three evolutionary conserved sites in the enhancer: HNF4-alpha (site 1), HNF1-alpha, HNF3-beta and an as yet unidentified TF (site 2) and the ubiquitously expressed TFs Sp1 and Sp3 (site 3). Mutagenesis studies showed that loss of binding of HNF3-beta resulted in a considerable decrease of enhancer activity, whereas loss of HNF4-alpha or Sp1/Sp3 resulted in milder reductions. The prothrombin enhancer plays a major role in regulation of prothrombin expression. Six different TFs are able to bind to this region. At least three of these TFs, HNF4-alpha, HNF3-beta and Sp1/Sp3, are important in regulation of prothrombin expression.


Missed hearing loss in tinnitus patients with normal audiograms.
The prevalence of tinnitus is positively correlated with hearing loss, although, tinnitus can also present alongside clinically normal pure-tone thresholds. As standard pure tone audiograms (PTA) only sample at octave or inter-octaves, they potentially can miss lesions between the tested frequencies. Here we investigate if tinnitus patients with normal audiograms have hearing loss missed by standard PTA testing, referred as "missed hearing loss" in the paper. Hearing thresholds in 106 tinnitus patients who have a normal PTA were tested using fine frequency resolution (1/24 octave step) audiometry, referred as precision PTA (P-PTA), at ±1/3 octave band centered at their tinnitus frequencies. Tinnitus pitch, loudness and residual inhibition were evaluated based on the result of P-PTA. DPOAEs were also tested to evaluate the function of outer hair cells (OHC). Using the P-PTA test, we found that 49% (52 out of 106) of tinnitus patients with normal audiograms showed sharply notched hearing loss and most of the notches were at their tinnitus frequencies. Using a fine frequency step (1/24 octave) to assess tinnitus pitch, the successful matching rate increased to 84%, significantly higher than the rate measured in traditional method (51%, Fisher's test, P < 0.0001, n = 106). The number of patients whose tinnitus loudness was less than 5 dB SL increased from 26% to 55% after the loudness reassessment based on the tinnitus pitch match (n = 106, Chi-Square test, P < 0.01). The percentage of patients who showed positive residual inhibition of tinnitus also increased from 31% to 54% (Chi-Square test, P < 0.05). DPOAEs revealed significantly reduced OAE amplitude in the tinnitus patients, suggesting that OHC dysfunction may contribute to their notched hearing loss. However, in 13 out of 31 patients with notched hearing loss, their DPOAE did not show any reduction which suggests that their notched hearing loss may be induced by the dysfunction of the inner hair cells or afferent synapses (synaptopathy). Our study confirmed hidden cochlear impairments in tinnitus patients with seemingly normal audiograms. We conclude that P-PTA can help identify a mild hearing impairment that may otherwise be missed by conventional PTA and that P-PTA can also improve tinnitus evaluation accuracy.


Effects of solids retention time on methanogenesis in anaerobic digestion of thickened mixed sludge.
When a bench-scale digester fed thickened mixed sludge was operated over an SRT range of 4-20 days, removal efficiencies for total chemical oxygen demand and volatile suspended solids declined with decreasing SRT (especially <10 days), but methanogenesis was stable for SRT as low as 5 days. Quantitative PCR analyses showed that methanogens declined steadily for SRT<10 days, with the acetate-cleaving Methanosaetaceae becoming more dominant. Clone-library analyses indicated significant shifts in bacterial population from 20 to 4 day SRT: declining Chloroflexi (28 to 4.5%) and Syntrophomonas (9 to 0%), but increasing Bacteroidetes (12.5 to 20%) and two acetogenic genera belonging to the phyla Firmicutes and Spirochaetales (6.3 to 12%). Thus, the decrease in the apparent hydrolysis constant (khyd-app) with higher SRT and the process limiting size of Methanosaetaceae with the lower SRT are proactive signs for defining rate limitation in anaerobic digestion.


Hormonal effects of tetrabromobisphenol A using a combination of in vitro and in vivo assays.
The aim of this study was to investigate the hormonal effects of tetrabromobisphenol A (TBBPA) in vitro on recombinant yeasts and in vivo on mosquitofish (Gambusia affinis). The in vitro bioassays for (anti-)androgenic activities showed that TBBPA had a weak androgenic activity in vitro with recombinant yeast systems carrying human androgen receptor (hAR). In the in vivo bioassays, the gene expression patterns of vitellogenin (Vtg), estrogen receptors (ERα and ERβ), and androgen receptors (ARα and ARβ) in adult males and juveniles after exposure to TBBPA for 60 days were evaluated. Significant up-regulation of Vtg, ERα, and ERβ mRNAs was observed in the liver after exposure to 500 nM of TBBPA. In the testis, the lowest concentration of TBBPA (50 nM) markedly induced Vtg, ERβ, and ARβ mRNA expression, but the same concentration significantly inhibited ARα mRNA expression. In addition, in juveniles, 100 nM of TBBPA significantly up-regulated the expression of Vtg, ERβ, and ARα mRNAs. However, TBPPA did not cause histological alterations in the liver and testis of adult male mosquitofish. The results from this present study suggest that TBBPA could display low but multiple hormonal activities despite its low toxicity to mosquitofish.


Short-term outcomes after transanal total mesorectal excision for rectal cancer in Denmark - a prospective multicentre study.
The aim of this study was to evaluate the short-term surgical and oncological outcomes after transanal total mesorectal excision (TaTME) for rectal cancer during the implementation phase of this procedure in Denmark. This is a retrospective review of prospectively recorded data. Registration was initiated by the Scientific Council of the Danish Colorectal Cancer Group (DCCG.dk) in order to assess the quality of care during the implementation of TaTME. Pre-, intra- and postoperative data including early recurrences were recorded at the operating centres. From August 2016 to April 2019, 115 TaTME procedures were registered. Patients were predominantly male (74%) with mid-rectal (88%) tumours. The level of surgical complications was comparable to previous nationwide results. Anastomotic leakage occurred in 6/109 (5.5%). One urethral injury occurred. The plane of dissection was mesorectal in 60% of cases, intramesorectal in 28% and muscularis in 12%. Nonmicroradicality was seen in 8% (R1, 6%; R2, 2%). Four local recurrences occurred after a median of 23 months of follow-up. One of these was multifocal. In an implementation phase where patient selection is expected, surgical and oncological results after TaTME were comparable to those of other approaches reported in the literature.


An acceptance and commitment therapy-based intervention for opioid use disorder risk in individuals with cancer: A treatment development study.
This paper describes the iterative development of an evidence-based behavioral intervention for individuals with cancer at risk for opioid use disorder, using the National Institutes of Health Stage Model for Behavioral Intervention Development. Adult patients with cancer from an outpatient palliative care clinic at an academic cancer center, with moderate to high risk of opioid misuse, were enrolled in a treatment development study that aimed to increase psychological flexibility. In this intervention, psychological flexibility is the posited mechanism of change for reduction of opioid use disorder risk. Patients completed baseline (pre-intervention) assessments, a six-session behavioral intervention based in Acceptance and Commitment Therapy, post-intervention assessments, and a semi-structured exit interview. Ten patients with moderate to high risk of opioid misuse completed the intervention. Patients rated the intervention as highly acceptable and were generally highly satisfied. Patients reported finding the coping skills helpful (e.g., mindfulness, cognitive defusion) and reported a preference for more sessions. These treatment development efforts have implications for the development and design of acceptance- and mindfulness-based, targeted interventions for individuals with cancer, receiving palliative care and at risk for opioid use disorder. Specifically, this six-session behavioral intervention to increase psychological flexibility was acceptable to patients and ready to be studied in a pilot RCT.


Implementation and utilization of hypofractionation for breast cancer.
Hypofractionation (HF) of whole breast irradiation has become a standard treatment regimen because randomized trials continue to demonstrate equivalence in survival and local control compared with conventional fractionation. In 2011, the American Society for Radiation Oncology (ASTRO) adopted clinical guidelines on the proper selection of HF. Nevertheless, utilization remains lower than predicted. We evaluate the effects of clinical directives that serve as default treatment decisions and prospective contouring rounds on the implementation of HF in a large, multicenter radiation oncology department. In 2010, we implemented consensus-driven and evidence-based clinical directives to guide treatment decisions. Five directives were available for adjuvant breast cancer treatment, including conventional fractionation and HF approaches, and were selected on the basis of disease specifics and clinical judgment. In 2012, we instituted prospective contouring rounds wherein the treating physicians presented their directive selection and patient contours for peer-review and consensus opinion. For this study, charts for patients with early stage breast cancer were reviewed. A total of 1043 cases of breast cancer were identified. Patients receiving HF were analyzed on the basis of the ASTRO 2011 guidelines and adherence to our more inclusive clinical directives. For the ASTRO-endorsed group (n = 685), 49% of patients received HF in 2011, and 80% received HF in 2015. For the directives-endorsed group (n = 1042), 47% of patients received HF in 2011, and 73% received HF in 2015. HF is underutilized despite equivalent local control, superior toxicity profile, and noninferior late effects. Our study demonstrates the possibility of achieving high levels of utilization in a large, multisite, outpatient setting. Factors responsible may include default rules established through the development of consensus-based treatment directives, peer review by faculty, and strong financial leadership to implement HF when indicated. To our knowledge, this is the first example of combining both consensus-based treatment directives and prospective contouring rounds in an attempt to change practice patterns.


A membrane-bound NAD(P)+-reducing hydrogenase provides reduced pyridine nucleotides during citrate fermentation by Klebsiella pneumoniae.
During anaerobic growth of Klebsiella pneumoniae on citrate, 9.4 mmol of H2/mol of citrate (4-kPa partial pressure) was formed at the end of growth besides acetate, formate, and CO2. Upon addition of NiCl2 (36 microM) to the growth medium, hydrogen formation increased about 36% to 14.8 mmol/mol of citrate (6 kPa), and the cell yield increased about 15%. Cells that had been harvested and washed under anoxic conditions exhibited an H2-dependent formation of NAD(P)H in vivo. The reduction of internal NAD(P)+ was also achieved by the addition of formate. In crude extracts, the H2:NAD+ oxidoreductase activity was 0.13 micromol min-1 mg-1, and 76% of this activity was found in the washed membrane fraction. The highest specific activities of the membrane fraction were observed in 50 mM potassium phosphate, with 1.6 micromol of NADPH formed min-1 mg-1 at pH 7.0 and 1.7 micromol of NADH formed min-1 mg-1 at pH 9.5. In the presence of the protonophore carbonyl cyanide m-chlorophenylhydrazone and the Na+/H+ antiporter monensin, the H2-dependent reduction of NAD+ by membrane vesicles decreased only slightly (about 16%). The NADP+- or NAD+-reducing hydrogenases were solubilized from the membranes with the detergent lauryldimethylamine-N-oxide or Triton X-100. NAD(P)H formation with H2 as electron donor, therefore, does not depend on an energized state of the membrane. It is proposed that hydrogen which is formed by K. pneumoniae during citrate fermentation is recaptured by a novel membrane-bound, oxygen-sensitive H2:NAD(P)+ oxidoreductase that provides reducing equivalents for the synthesis of cell material.


Participation of interferons in psoriatic inflammation.
Interferons are multifunctional cytokines not expressed in the skin under normal physiological conditions. However, they are overexpressed in serum and skin lesions of patients with psoriasis and play an important role in the pathogenesis of the disease. Interferons act directly on skin resident cells and recruit and modulate inflammatory cells, thereby exacerbating psoriatic inflammation. They upregulate the expression of relevant cytokines and chemokines, facilitate excessive proliferation of keratinocytes, and enhance the formation of poorly differentiated dermal microvessels. In this review, we summarized the pathogenic effect of interferons on psoriasis and also discussed the therapeutic strategies targeting interferons.


Efficacy of a new Activation Device in Irrigant Penetration Into Simulated Lateral Canals.
The aim of the present study was to compare the effects of EasyClean (EC) on irrigant delivery into simulated lateral canals using an artificial closed canal system. Passive ultrasonic irrigation (PUI) was used as a reference technique for comparison. Forty simulated curved root canals manufactured in transparent resin and with simulated lateral canals were instrumented with Reciproc R40 files and randomly assigned to four groups (n=10) according to the irrigant activation technique: PUI group, ECrec group (EC used in reciprocating motion), ECrot group (EC used in rotary motion), and control group (no activation performed). After activation, stereomicroscope images from each block were taken, and irrigant penetration into lateral canals was measured using Adobe Photoshop software. Data were analysed using ANOVA and Tukey's post hoc test (α=0.05). No penetration was observed in the control group. The ECrec group showed lower penetration than the other group (P<0.05). No differences were observed between the ECrot group and the PUI group (P>0.05). EC used in rotary motion was effective in increasing the penetration of the irrigating solution into simulated lateral canals.


Occupational risk of nano-biomaterials: Assessment of nano-enabled magnetite contrast agent using the BIORIMA Decision Support System.
The assessment of the safety of nano-biomedical products for patients is an essential prerequisite for their market authorization. However, it is also required to ensure the safety of the workers who may be unintentionally exposed to the nano-biomaterials (NBMs) in these medical applications during their synthesis, formulation into products and end-of-life processing and also of the medical professionals (e.g., nurses, doctors, dentists) using the products for treating patients. There is only a handful of workplace risk assessments focussing on NBMs used in medical applications. Our goal is to contribute to increasing the knowledge in this area by assessing the occupational risks of magnetite (Fe3O4) nanoparticles coated with PLGA-b-PEG-COOH used as contrast agent in magnetic resonance imaging (MRI) by applying the software-based Decision Support System (DSS) which was developed in the EU H2020 project BIORIMA. The occupational risk assessment was performed according to regulatory requirements and using state-of-the-art models for hazard and exposure assessment, which are part of the DSS. Exposure scenarios for each life cycle stage were developed using data from literature, inputs from partnering industries and results of a questionnaire distributed to healthcare professionals, i.e., physicians, nurses, technicians working with contrast agents for MRI. Exposure concentrations were obtained either from predictive exposure models or monitoring campaigns designed specifically for this study. Derived No-Effect Levels (DNELs) were calculated by means of the APROBA tool starting from in vivo hazard data from literature. The exposure estimates/measurements and the DNELs were used to perform probabilistic risk characterisation for the formulated exposure scenarios, including uncertainty analysis. The obtained results revealed negligible risks for workers along the life cycle of magnetite NBMs used as contrast agent for the diagnosis of tumour cells in all exposure scenarios except in one when risk is considered acceptable after the adoption of specific risk management measures. The study also demonstrated the added value of using the BIORIMA DSS for quantification and communication of occupational risks of nano-biomedical applications and the associated uncertainties.


Immunochemical Detection of Modified Species of Cytosine in Plant Tissues.
Methylated cytosine (5-methylcytosine) is the most studied epigenetic mark involved in the regulation of gene expression. Although it displays highly variable dynamics during plant ontogenesis, it is possible to gain a fine spatial perspective with immunohistochemistry techniques that use specific antibodies and fluorochromes. Besides, there are other cytosine modifications described in plants, although their biological significance is still unknown (i.e., 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine). Here we present a standardized protocol to detect cytosine modifications in plant tissues.


Hepatic infarction and acute liver failure in children with extrahepatic biliary atresia and cirrhosis.
Acute hepatic failure developed in four patients (aged 7 to 13 months) who had extrahepatic biliary atresia treated initially by portoenterostomy. Two were stable outpatients with minimal jaundice, while the other two were hospitalized for metabolic or nutritional complications. Postmortem examination in each patient revealed massive acute hepatic infarction with few surviving hepatocytes. In all cases, the hepatic failure had been preceded by an episode of hypotension and/or hypovolemia. The exact pathogenesis of the infarction remains unclear but it may be related to decreased hepatic blood flow secondary to biliary obstruction. The only effective treatment for these patients is intensive supportive care and urgent liver transplantation.


Milk and serum progesterone levels in mares after ovulation.
Twenty-four Finnhorse mares were examined by rectal palpation and ultrasonography every 6 h during late oestrus to determine the time of ovulation. Milk and serum samples were collected every 6 h after the detected ovulation for progesterone analysis. The progesterone rises took place within 0-54 h and 0-60 h after ovulation, in milk and serum, respectively. Statistically significant differences (p less than 0.05) in progesterone levels were observed for the first time 12-18 h and 18-24 h after ovulation, in serum and milk, respectively, as compared to progesterone levels 0-6 h after ovulation.


How does the fiscal pressure of local governments affect China's PM2.5 emissions?
Affected by the epidemic and other factors, the global economy is in a downturn, and countries around the world are under unprecedented debt pressure. How will this affect environmental protection? Taking China as an example, this paper empirically studies the impact of changes in local government behavior on urban air quality under fiscal pressure. This paper uses the generalized method of moments (GMM) to find that fiscal pressure has significantly reduced PM2.5 emissions, with a unit increase in fiscal pressure will increase PM2.5 by about 2%. The mechanism verification shows that three channels affect PM2.5 emissions: (1) fiscal pressure has prompted local governments to relax the supervision of existing pollution-intensive enterprises. (2) Local governments reduce environmental regulations for attracting more pollution-intensive enterprises. (3) Local governments tend to reduce environmental protection investment to save fiscal expenses. The paper's conclusions provide new policy ideas for promoting environmental protection in China, as well as served as a case for analyzing current changes in environmental protection in other countries.


Hepatozoon ursi n. sp. (Apicomplexa: Hepatozoidae) in Japanese black bear (Ursus thibetanus japonicus).
Morphological and genetic features of a new Hepatozoon species, Hepatozoon ursi n. sp., in Japanese black bear (Ursus thibetanus japonicus) were studied. Schizogonic developmental stages were observed in the lungs of Japanese black bears. The schizonts were sub-spherical in shape and 45.7+/-4.6 x 42.7+/-4.5 microm in size. Each mature schizont contained approximately 80-130 merozoites and 0-5 residual bodies. The merozoites were 7.0+/-0.7 x 1.8+/-0.3 microm in size. Intraleukocytic gametocytes were slightly curved, cigar-like in shape and had a beak-like protrusion at one end. The size of the gametocytes was 10.9+/-0.3 x 3.3+/-0.2 microm. The analyses of the18S rRNA gene sequences supported the hypothesis that H. ursi n. sp. is different from other Hepatozoon species. Mature Hepatozoon oocysts were detected in two species of ticks (Haemaphysalis japonica and Haemaphysalis flava) collected on the bears infected with H. ursi n. sp. Two measured oocysts were 263.2 x 234.0 microm and 331.8 x 231.7 microm, respectively. The oocysts contained approximately 40 and 50 sporocysts, respectively. The sporocysts were sub-spherical in shape and 31.2+/-2.5 x 27.0+/-2.9 microm in size. Each sporocyst contained at least 8-16 sporozoites, with the sporozoites being 12.2+/-1.4 x 3.5+/-0.5 microm in size. H. ursi n. sp. is the first Hepatozoon species recorded from the family Ursidae.


Myoglobinemia in children with progressive muscular dystrophy.
Out of 13 patients with congenital muscular dystrophy myoglobinemia was proven in four, and nine of 13 cases of Duchenne dystrophy showed myoglobinemia by counterimmunoelectrophoretic technique. Serum myoglobin was positive in 14 out of 15 patients whose serum creatinine phosphokinase (CPK) levels rose above 2500 units, whereas positive myoglobinemia was obtained in only one patient in eleven with lower CPK levels. All the myoglobinemic patients were less than 5 years of age in the case of congenital muscular dystrophy and less than 9 years of age in the case of Duchenne dystrophy. Thus, the leakage of myoglobin into the serum from the damaged muscle seemed closely correlated to the age of the patients and level of serum CPK, but not to the type of disease.


A gastrointestinal stromal tumor at the esophagogastric junction successfully treated by laparoscopic wedge resection with seromuscular layer dissection: a case report.
Herein, we report a case of a gastrointestinal stromal tumor (GIST) at the esophagogastric junction (EGJ) that was successfully treated by a laparoscopic wedge resection (LWR) after dissection of the seromuscular layer around the tumor to prevent postoperative deformities and stenosis of the EGJ. Subsequently, the abdominal esophagus was wrapped by the gastric fornix according to Dor's method in order to prevent reflux esophagitis after surgery.A 71-year-old female patient was admitted with a diagnosis of a GIST (23 × 20 × 20 mm) at the EGJ. We performed the abovementioned operation.Gastroduodenal endoscopic examination revealed no deformity or stenosis of the EGJ at 6 months after the operation. The patient has not experienced any reflux symptoms. Tumor recurrence was not noted 26 months after the operation.This procedure is useful in preventing the deformity and stenosis of the EGJ as well as postoperative reflux esophagitis.


Methemoglobinemia due to ingestion of at most three pills of pyridium in a 2-year-old: case report and review.
Pyridium (phenazopyridine HCl) is a commonly prescribed medication in the treatment of urinary tract infections and is known to cause methemoglobinemia in excessive doses. We report the case of a 2-year-old child who ingested a maximum of three 200-mg tablets (approximately 50 mg/kg) of pyridium and yet developed cyanosis and methemoglobinemia (29.1%), resulting in methylene blue therapy. We urge physicians to consider a period of observation (4-6 h) or to obtain methemoglobin levels in children who ingest even a small number of pyridium tablets because this can represent a toxic dose in a small child.


An Antibiotic-Free Model of Candida albicans Colonization of the Murine Gastrointestinal Tract.
The human gastrointestinal (GI) tract is home to trillions of commensal organisms. Some of these microbes have the capacity to become pathogenic following changes in the microenvironment and/or host physiology. Candida albicans is one such organism, usually inhabiting the GI tract as a harmless commensal in most individuals but with the potential to cause serious infection. Risk factors for C. albicans GI infections include the use of antibiotics, neutropenia, and abdominal surgery. Understanding how commensal organisms can transform into life-threatening pathogens is an important area of research. Mouse models of fungal GI colonization provide an essential platform to study the mechanisms involved in the transition of C. albicans from benign commensal to dangerous pathogen. This chapter presents a novel method of stable, long-term colonization of the murine GI tract with Candida albicans.


[Return to pivot-contact sports after anterior cruciate ligament reconstruction: patellar tendon or hamstring autografts].
The purpose of this study was to compare outcome at 12 months and return of pivot-contact sports in male subjects having undergone anterior cruciate ligament reconstruction using a patellar tendon or four-strand hamstring autografts. Sixty male athletes underwent arthroscopic ligament reconstruction using either a patellar graft or a hamstring graft. The two groups were comparable for age (25+/-6 years), height (177+/-5cm), weight (74+/-8kg), pivot-contact sports, and level of sports activity. The two groups were reviewed at four, six and 12 months. The Lysholm and Tegner scores were noted and isokinetic tests were performed (60 and 180 degrees /s). The comparison was completed at twelve months with the single-legged hop test, instrumental laximetry (KT-1000) and the Arpege and IKDC 2000 scores. Return to pivot-contact sports at the same level was assessed at last follow-up after having been encouraged at the nine-month check-up. At twelve months, the function scores (IKDC 2000, Lysholm: 99.4+/-5 versus 98+/-5, Tegner: 6.8+/-1 versus 6.5+/-1) and single-legged hop test (94+/-5% versus 95+/-7%) were comparable. Instrumental laxity measurements however demonstrated greater laxity with the hamstring graft (2.7+/-0.4mm versus 1.8+/-0.3mm, p=0.02). A knee extension deficit was observed for the patellar technique (10+/-8%, p<0.01). A knee flexion deficit was observed for the hamstring technique (11+/-14%, p<0.01). Return to pivot-contact sports at the same level was comparable and concerned 53% [95%CI 41-66] of the knees after hamstring ligament reconstruction and 56.6% [44-68] of the knees after patellar ligamentoplasty. The two techniques of anterior cruciate ligament reconstruction were found to be equivalent in terms of return to pivot-contact sports at the same level. It was noted however that this resumed sports activity was possible for only one out of two subjects despite the systematic medical and surgical surveillance and selection of subjects free of any complication.


Attitudes of Lebanese university students towards surgical hymen reconstruction.
Many cultural and religious beliefs place virginity at a high level of social significance, in that women who lose their virginity before marriage may face humiliation, ostracism, divorce, and extreme violence. This led to an increase in the demand for virginity restoration through surgical hymen reconstruction among these cultures. However, data regarding the acceptance of hymenoplasty in societies that consider sexuality a taboo are scarce. In this cross-sectional study, we investigated the effects of gender and religion on sexual attitudes towards hymenoplasty, premarital sex, and virginity in a sample of 600 Lebanese university students. Our findings showed that approval of hymenoplasty was low among participants regardless of gender (25.7 % men vs. 19.1 % women) and religious affiliations (22.5 % Muslims vs. 22.3 % Christians). Arguments for rejection were rooted in moral ethics and personal convictions: "form of deceiving and cheating" (80.7 %) and "betrayal of honesty in the relationship" (80.4 %). Reasons for acceptance included: personal belief in "women's rights, autonomy, and freedom" (72.2 %) and "physical harm and death" (63.5 %).Male participants were more likely to approve premarital coital sex than females (61.0 vs. 27.3 %). Muslims were also more likely to reject marrying a non-virgin than Christians (39.9 vs. 18.0 %). Female participants expressed more tolerance towards marrying a non-virgin male partner (78.3 vs. 57.3 %). Low acceptance of hymenoplasty among Lebanese university students was found to be related to moral ethics and personal convictions independently from gender and religious affiliation. Differences in sexual attitudes towards premarital coital sex and virginity, however, were more significantly influenced by culture and religion.


Bite force and pattern measurements for dental pain assessment in the rat.
We present simple method to assess dental pain in the awake rat. Using a sensitive strain gauge we examined changes in bite strength and bite pattern in rats following dental injury. Rats with dental injury displayed a significant reduction in mean peak bite strength and an altered bite cluster pattern. Both changes in the dental injury rats were reversed by an analgesic dose of morphine, and this could be reversed with naloxone. These changes were not observed in naive control animals. This simple method significantly improves our ability to evaluate dental pain syndromes.


Pulmonary physiotherapy in neonates: physiologic changes and respiratory management.
To investigate physiologic alterations in respiratory function associated with chest physiotherapy, arterial blood gases, respiratory patterns, lung mechanics, and functional residual capacity were measured in 13 neonates (weights 1.25 to 3.20 kg) during the control period, after vibration of the chest and suctioning, after hyperventilation, and two hours after suctioning. Compared to control values, mean PO2decreased significantly after suctioning to 43 mm Hg and increased significantly after hyperventilation to 78 mm Hg. There was a significant decrease in inspiratory resistance and a trend toward decrease in expiratory resistance after suctioning, with return to control levels after hyperventilation. Respiratory rate increased significantly after suctioning. Functional residual capacity, dynamic lung compliance, and tidal volume, as well as PCO2 and base excess, were not changed appreciably throughout the protocol. Because of potentially severe hypoxemia, this study suggests that suctioning and hyperventilation are not warranted on a routine basis in infants recovering from respiratory diseases.


[Roles of glial cell line-derived neurotropic factor in motoneuron development and motoneuron disease].
To review research progress of the relation between glial cell line-derived neurotropic factor (GDNF) and motor neuron development and motor neuron disease. The recent articles on GDNF and motor neurons were extensively reviewed. The molecular structure, the mode of action and the route of administration of GDNF were investigated. GDNF plays extensive roles in the development and disease of motor neuron. GDNF might regulate the development of the motor neurons of the spinal cord to some extent and also save the injured motor neurons. GDNF has a potential clinical value and inestimable future in the treatment of motor neuron diseases.


mRNA splicing efficiency in yeast and the contribution of nonconserved sequences.
A simple kinetic model for mRNA splicing predicts the way in which in vivo steady state precursor RNA levels (P) and messenger RNA levels (M) vary as a function of the rate constant of the splicing reaction (ksp). The model points to M/P as the best measure of ksp. The analysis of a set of intron mutations in a yeast gene supports the general features of the model and shows that the splicing efficiency of transcripts containing the wild-type intron is well in excess of what is necessary to generate normal mRNA levels. The data also suggest that regions of the intron, in addition to the well-conserved consensus sequences, contribute to efficient splicing.


Templated Generation of a Bcl-xL Inhibitor by Isomer-Free SPAAC Based on Azacyclonon-5-yne.
High-affinity inhibitors of large protein-protein interactions often have a high molecular weight, which compromises their cell permeability and oral bioavailability. We recently presented isomer-free, strain-promoted azide-alkyne cycloaddition (iSPAAC) as a method by which to generate large, chemically uniform bioactive molecules inside living cells from two smaller components with higher cell permeability. Here, we present the synthesis of Fmoc-protected azacyclonon-5-yne (Fmoc-ACN) as the first cyclononyne suitable for iSPAAC. ACN facilitated the structure-guided development of a single-digit micromolar triazole inhibitor of the protein-protein interaction domain of the antiapoptotic protein Bcl-xL . Inhibitor formation in aqueous buffer at 37 °C, templated by the target protein Bcl-xL , proceeded 2800 times faster than the reaction between Fmoc-ACN and benzyl azide under standard conditions in acetonitrile. Our data demonstrate the utility of cyclononynes for iSPAAC and their potential for achieving vastly accelerated templated reactions in aqueous environments.