[Recent advances in studying the chemical constituents of Panax ginseng C.A. Mey].
The paper reports a survey of the chemical constituents of Panax ginseng, emphasizing ginseng saponin, polysaccharide, essential oil, and polypeptide, with 30 references.


Novel Clinical Insights into Spinal Hemangioblastoma in Adults: A Systematic Review.
Hemangioblastomas (HBs) are well-vascularized, benign central nervous system tumors and the third most common primary spinal cord tumor after astrocytoma/ependymoma, occurring sporadically or as a part of autosomal dominant von Hippel-Lindau disease, in which tumors are often multiple and prone to relapse. Spinal HBs are commonly located in the cervical cord and associated with a syrinx formation. Owing to location and growth trends, they may cause significant neurological deficit, impairing quality of life. We conducted a systematic review to understand better clinical insights into spinal HB in adults and compare spinal HB versus posterior cranial fossa HB. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for conducting systematic reviews, we reviewed the English-language literature on adult spinal HB in the MEDLINE/PubMed database over the last 40 years. We reviewed 237 articles on adult spinal HB and analyzed national and continental distribution, clinical symptoms, tumor location and presence of syringomyelia, treatment strategies and postoperative complications, histology and immunochemistry, and treatment outcomes. We compared individual characteristics in sporadic and von Hippel-Lindau disease spinal HBs. Finally, we compared features of posterior cranial fossa and spinal HBs. Spinal cord HBs most commonly have a dorsal intramedullary location. Total surgical tumor resection is the first treatment option; preoperative embolization may be performed to reduce intraoperative bleeding and surgical time. HBs located in the spine have decreased mortality and rate of infection, but increased rates of cardiopulmonary complications compared with HBs in the posterior cranial fossa.


Peripheral seventh nerve palsy due to transorbital intracranial penetrating pontine injury.
The case of a child injured by a knitting needle penetrating transorbitally and intracranially, resulting in carotid cavernous fistula and pontine injury, is reported. After receiving medical and endovascular treatment, the only remaining abnormal neurological manifestation was right peripheral facial nerve palsy. The clinical sequences of events and the demonstration of a pontine lesion leading to peripheral facial palsy are presented. Facial nuclear injury with a penetrating trauma is an extremely rare condition. It is important to identify the anatomical regions injured in penetrating traumas. The lesions must be identified by computerized tomography, magnetic resonance imaging, clinical and laboratory investigation.


Synonymous Codons: Choose Wisely for Expression.
The genetic code, which defines the amino acid sequence of a protein, also contains information that influences the rate and efficiency of translation. Neither the mechanisms nor functions of codon-mediated regulation were well understood. The prevailing model was that the slow translation of codons decoded by rare tRNAs reduces efficiency. Recent genome-wide analyses have clarified several issues. Specific codons and codon combinations modulate ribosome speed and facilitate protein folding. However, tRNA availability is not the sole determinant of rate; rather, interactions between adjacent codons and wobble base pairing are key. One mechanism linking translation efficiency and codon use is that slower decoding is coupled to reduced mRNA stability. Changes in tRNA supply mediate biological regulationfor instance,, changes in tRNA amounts facilitate cancer metastasis.


An Investigation into the Potential Therapeutic Effects of the Qigu Zhushui Decoction on Mouse Models of Malignant Ascites.
To determine whether or not a decoction made from Qigu Zhushui has a suppressive impact on malignant ascites in mice. Malignant ascites are one of the common complications of advanced malignant tumors. Patients with malignant ascites typically have a poor prognosis, with only 12 to 20 weeks of survival. Currently, the standard treatments for malignant ascites are systemic chemotherapy, which is ineffective in eradicating the disease and is associated with issues such as safety, short duration of sustained high-level drug concentration in localised regions, and drug resistance. To clarify the effect of Qigu Zhushui decoction on inhibiting malignant ascites in mice and provide the experimental basis for further research. The ascites model of liver cancer in mice was established by intraperitoneal injection of the H22-H8D8 cell line of liver cancer. ELISA detected the content of CEA, VEGF and TNF-α in ascites. Qigu Zhushui decoction combined with cisplatin group and Qigu Zhushui decoction highdose group could significantly reduce the weight, abdominal circumference and ascites volume of mice, and their survival days and survival rate were also greatly improved; The levels of CEA and VEGF in the combination group decreased significantly, while the level of TNF-α increased; The level of TNF-a in the high dose group of Qigu Zhushui decoction was significantly increased, while the level of CEA and VEGF in the moderate dose group was decreased. Qigu Zhushui decoction can reduce the malignant ascites in mice, and the combination of Qigu Zhushui decoction and cisplatin has a significant anti-malignant ascites effect, which can significantly prolong the survival time and improve the survival rate.


ThPOD3, a truncated polypeptide from Tamarix hispida, conferred drought tolerance in Escherichia coli.
The ThPOD1 gene encodes a peroxidase and was isolated from a Tamarix hispida NaCl-stress root cDNA library. We found that ThPOD1 expression could be induced by abiotic stresses such as cold, salt, drought and exogenous abscisic acid. These findings suggested that ThPOD1 might be involved in the plant response to environmental stresses and ABA treatment. To elucidate the function of this gene, recombinant plasmids expressing full-length ThPOD1 as well as ThPOD2 (aa 41-337), and ThPOD3 (aa 73-337) truncated polypeptides were constructed. SDS-PAGE and Western blot analyses of the fusion proteins revealed that the molecular weights of ThPOD1, ThPOD2 and ThPOD3 were approximately 57, approximately 50 and approximately 47 kDa, respectively. Stress assays of E. coli treated with the recombinant plasmids indicated that ThPOD3 could improve resistance to drought stress. This finding could potentially be used to improve plant tolerance to drought stress via gene transfer.


Influence of soluble copper on the electrokinetic properties and transport of copper oxychloride-based fungicide particles.
This article describes the influence of dissolved copper on the electrokinetic properties and transport of a copper oxychloride-based fungicide (COF) in porous media. The Zeta potential (ζ) of COF particles increases (viz. becomes less negative) with increasing concentration of Cu(2+) in the bulk solution. ζ decreases for COF when the electrolyte (NaNO(3)) concentration is raised from 1 to 10mM. This can be ascribed to ion correlation of Cu(2+) in the electrical double layer (EDL). COF transport tests in quartz sand columns showed the addition of Cu(2+) to the bulk solution to result in increased retention of the metal. Modelling particle deposition dynamics provided results consistent with kinetic attachment. Based on the effect of soluble Cu on colloid mobility, the transport of particulate and soluble forms of copper is coupled via the chemistry of pore water and colloid interactions. Mutual effects between cations and colloids should thus be considered when determining the environmental fate of particulate and soluble forms of copper in soil and groundwater (especially at copper-contaminated sites).


Recovery from a near-lethal exposure to ultraviolet-C radiation in a scleractinian coral.
Hermatypic (reef building) corals live in an environment characterized by high ambient levels of photosynthetically active radiation (PAR) and ultraviolet radiation (UVR). Photoadaptive mechanisms have evolved to protect the sensitive cell structures of the host coral and their photosynthetic, endosymbiotic zooxanthellae. Environmental stressors may destabilize the coral-zooxanthellae system resulting in the expulsion of zooxanthellae and/or loss of photosynthetic pigment within zooxanthellae, causing a condition known as bleaching. It is estimated that 1% of the world's coral population is lost yearly, partly due to bleaching. Despite intensive research efforts, a single unified mechanism cannot explain this phenomenon. Although UVA and UVB cellular damage is well documented, UVC damage is rarely reported due to its almost complete absorption in the stratosphere. A small scale coral propagation system at the University of Maine was accidentally exposed to 15.5h of UVC radiation (253.7 nm) from a G15T8 germicidal lamp, resulting in a cumulative surface irradiance of 8.39 x 10(4) J m(-2). An experiment was designed to monitor the progression of UVC induced damage. Branch sections from affected scleractinian corals, Acropora yongei and Acropora formosa were submitted to histopathology to provide an historical record of tissue response. The death of gastrodermal cells and necrosis resulted in the release of intracellular zooxanthellae into the gastrovascular canals. Zooxanthellae were also injured as evidenced by pale coloration, increased vacuolization and loss of membrane integrity. The recovery of damaged coral tissue likely proceeds by re-epithelialization and zooxanthellae repopulation of gastrodermal cells by adjacent healthy tissue.


Efficacy and safety of free medial plantar flap in repair of the high-voltage electrical burns in hands.
The purpose of this work was to validate the efficacy and safety of free medial plantar flap in repair of hand wounds resulted from high-voltage electrical burn. 22 patients with high-voltage electrical burn wounds were retrieved between July 2016 and July 2018 in the Affiliated Zhengzhou Central Hospital of Zhengzhou University. All the wounds were the entrance of high-voltage electrical current. After thorough debridement, the blood vessels, nerves, tendons, joints were exposed to defects with different degrees. The soft tissue defects were repaired with the free medial plantar flap repair in 12 patients and medium-thickness skin graft in 10 patients. Postoperative management was similar between the two groups. All the operations were completed within 6 h. In the free medial plantar flap group, the mean follow-up period was (11.3 ± 2.4) months, ranging from 9 to 15 months, and all flaps survived; there were no vessel crises. Flaps of 10 patients healed without any complications, and local necrosis occurred in two cases, with healing after debridement. The two-point discrimination (TPD) was 7.0-11.0 mm, and the mean DASH score was 45.6 ± 7.4. In the medium-thickness skin graft group, the mean follow-up period was (10.9 ± 1.8) months. All flaps survived, and local contracture occurred in 3 cases. The TPD was 8.0-11.0 mm, and the mean DASH score was 60.7 ± 9.3. The free medial plantar flap is an ideal option for repairing the hand soft defects resulted from the high-voltage electrical burn.


How etiological explanations for depression impact perceptions of stigma, treatment effectiveness, and controllability of depression.
There is controversy regarding how etiological explanations for depression, particularly biological explanations, influence perceptions of stigma, perceived controllability of depression, and perceived effectiveness of depression treatments. This study evaluated how biological and psychosocial explanations for depression relate to these variables. Undergraduate students who reported ever suffering from clinical depression (n = 36) and who reported no personal history of depression (n = 33) completed a diagnostic interview and questionnaires assessing etiology beliefs, stigma perceptions, perceived controllability of depression, and perceived effectiveness of different depression treatments. Although "ever depressed" participants perceived more stigma than "never depressed" participants, endorsing either etiological model had little relation to perceived stigma. Endorsing psychosocial explanations was associated with perceiving self-initiated treatments as effective, and self-initiated treatments were viewed as more effective than either psychotherapy or medical interventions. Stigmatizing attitudes about depression appear more meaningfully related to individuals' personal experiences with depression than to etiological explanations for depression; yet etiological models appear to have important implications for treatment preference and perceived controllability of mood.


Pyroptosis and the tumor immune microenvironment: A new battlefield in ovarian cancer treatment.
Ovarian cancer is a less common tumor in women compared to cervical or breast cancer, however it is more malignant and has worse outcomes. Ovarian cancer patients still have a five-year survival rate < 50% despite advances in therapy. Due to recent developments in immune checkpoint inhibitors (ICIs), cancer immunotherapy has attracted increased interest. Pyroptosis is a highly inflammatory form of cell death, which is essential for bridging innate and adaptive immunity, and is involved in immune regulation within the tumor microenvironment (TME). Recent research has shown that pyroptosis can promote immunotherapy of ovarian cancer, including treatment with chimeric antigen receptor T-cells (CAR-T) or ICIs. Moreover, inflammasomes, various signaling pathways and lncRNAs can all affect pyroptosis in ovarian cancer. Here we discuss how pyroptosis affects the development and progression of ovarian cancer as well as the TME. We also provide a summary of small molecule drugs that could target pyroptotic cell death processes and may be useful in ovarian cancer therapy.


Intracranial nasal natural killer/T-cell lymphoma: immunopathologically-confirmed case and review of literature.
Advances in immunophenotypic profiling now permit characterization of natural killer/T-cell (NK/T-cell) lymphoma as distinct from other extranodal T- and B-cell Non-Hodgkin's lymphomas. NK/T-cell lymphoma presents most commonly in the nasal cavity. Disease progression to the central nervous system (CNS) is a rare phenomenon. We present here, to our knowledge, the first immunophenotypically-confirmed case of direct extension of nasal NK/T-cell lymphoma to the brain. In addition, we review the literature with respect to NK/T-cell lymphoma metastasis to the CNS. The overall prevalence of NK/T-cell lymphoma CNS metastasis is less than 3%. Although rare, CNS invasion portends a poor prognosis, emphasizing the importance of early and accurate immunophenotype profiling and the need for novel, aggressive therapy.


In vitro and in vivo assessment of the anti-malarial activity of Caesalpinia pluviosa.
To overcome the problem of increasing drug resistance, traditional medicines are an important source for potential new anti-malarials. Caesalpinia pluviosa, commonly named "sibipiruna", originates from Brazil and possess multiple therapeutic properties, including anti-malarial activity. Crude extract (CE) was obtained from stem bark by purification using different solvents, resulting in seven fractions. An MTT assay was performed to evaluate cytotoxicity in MCF-7 cells. The CE and its fractions were tested in vitro against chloroquine-sensitive (3D7) and -resistant (S20) strains of Plasmodium falciparum and in vivo in Plasmodium chabaudi-infected mice. In vitro interaction with artesunate and the active C. pluviosa fractions was assessed, and mass spectrometry analyses were conducted. At non-toxic concentrations, the 100% ethanolic (F4) and 50% methanolic (F5) fractions possessed significant anti-malarial activity against both 3D7 and S20 strains. Drug interaction assays with artesunate showed a synergistic interaction with the F4. Four days of treatment with this fraction significantly inhibited parasitaemia in mice in a dose-dependent manner. Mass spectrometry analyses revealed the presence of an ion corresponding to m/z 303.0450, suggesting the presence of quercetin. However, a second set of analyses, with a quercetin standard, showed distinct ions of m/z 137 and 153. The findings show that the F4 fraction of C. pluviosa exhibits anti-malarial activity in vitro at non-toxic concentrations, which was potentiated in the presence of artesunate. Moreover, this anti-malarial activity was also sustained in vivo after treatment of infected mice. Finally, mass spectrometry analyses suggest that a new compound, most likely an isomer of quercetin, is responsible for the anti-malarial activity of the F4.


Selective serotonin reuptake inhibitors and preeclampsia: A quality assessment and meta-analysis.
Serotonin modulates vascular, immune, and neurophysiology and is dysregulated in preeclampsia. Despite biological plausibility that selective serotonin reuptake inhibitors (SSRIs) prevent preeclampsia pathophysiology, observational studies have indicated increased risk and providers may be hesitant. The objective of this meta-analysis and quality assessment was to evaluate the evidence linking SSRI use in pregnancy to preeclampsia/gestational hypertension. PubMed was searched through June 5, 2020 manually and using combinations of terms: "preeclampsia", "serotonin", and "SSRI". This review followed MOOSE guidelines. Inclusion criteria were: 1) Observational cohort or population study, 2) exposure defined as SSRI use during pregnancy, 3) cases defined as preeclampsia or gestational hypertension, and 4) human participants. Studies were selected that addressed the hypothesis that gestational SSRI use modulates preeclampsia and/or gestational hypertension risk. Review Manager Web was used to synthesize study findings. Articles were read and scored (Newcastle-Ottawa Quality Assessment Scale) for quality by two independent reviewers. Publication bias was assessed using a funnel plot and the Egger test. Of 179 screened studies, nine were included. The pooled risk ratio (random effects model) was 1.43 (95 % CI: 1.15-1.78, P < 0.001; range 0.96-4.86). Two studies were rated as moderate quality (both with total score of 6); others were high quality. Heterogeneity was high (I2 = 88 %) and funnel asymmetry was significant (p < 0.00001). Despite evidence for increased preeclampsia risk with SSRIs, shared risk factors and other variables are poorly controlled. Depression treatment should not be withheld due to perceived gestational hypertension risk. Mechanistic evidence for serotonin modulation in preeclampsia demonstrates a need for future research.


GJB2 mutations in Iranian Azeri population with autosomal recessive nonsyndromic hearing loss (ARNSHL): First report of c.238 C>A mutation in Iran.
Autosomal-recessive nonsyndromic hearing loss (ARNSHL) is a heterogeneous genetic disorder. Mutations in the gap junction protein beta 2 (GJB2) gene, encoding connexin 26, are a significant cause of ARNSHL in different ethnic groups. This study aimed to identify the frequency and type of GJB2 mutations in the Iranian Azeri population. Fifty unrelated families presenting ARNSHL in Ardabil Province, the northwest of Iran, were studied to determine the frequency and type of GJB2 mutations leading to ARNSHL. ARMS-PCR screened all DNA samples to detect c.35delG; p. Gly12Val mutation. In addition, normal samples for c.35delG; p. Gly12Val were analyzed by direct sequencing for other GJB2 mutations. Of the fifty families, 13 (26%) showed a GJB2 gene mutation, with c.35delG; p. Gly12Val mutation was the most prevalent one that occurred in eight (61.5%) out of the 13 families. Of the families, two were homozygous for c.358-360delGAC; p. Glu120del mutation, and one was homozygous for c.290dupA; p. Tyr97Ter and c.299-300delAT; p. His100Arg mutations. Also, we detected a novel mutation, c.238C>A; p. Gln80lys, in one of the families. Our findings are comparable to previous studies, indicating c.35d3lG; p. Gly12Val mutation in the GJB2 gene is the most common cause of GJB2-related hearing loss in the Iranian Azeri population. Furthermore, our study highlights the significance of ARNSHL screening programs of live births based on local population data in Iran.


Swept-source optical coherence tomography angiography vitreo-retinal segmentation in proliferative diabetic retinopathy.
To identify a new cortical vitreous segmentation protocol for non invasive standardised investigation of Neovascularisation (NV) with detection of regression of NV activity in Proliferative Diabetic Retinopathy (PDR). Retrospective study. One hundred and eighty-six eyes of 93 consecutive diabetic patients (mean age: 52.6 ± 11.0 years) imaged using Topcon Triton® Swept-Source Optical Coherence Tomography Angiography (SS-OCTA) from June 2015 to January 2017. Scans were performed through the macula, optic disc and areas of possible NV in mid-peripheral retina using 6 × 6 mm and/or 9 × 9 mm raster-patterns in three segmentation protocols: Vitreo-Retinal (VRS), Outer-Vitreous (OVS) and Core-Vitreous Segmentation (CVS). Any suspicion of PDR was confirmed in all patients by Heidelberg® Widefield-Fundus-Fluorescein-Angiography (WF-FFA) and/or Optos® Ultra-WF-FFA (UWF-FFA). Inter-observer reproducibility of NV diagnosis and agreement between SS-OCTA and UWF-FFA were assessed. Primary outcome was the identification of an effective and reproducible segmentation protocol. Secondary outcome was the identification of NV regression after treatment. Sensitivity-specificity reached, respectively, the value of 100 to 100 in detecting NVD, and 96.6 to 100 in detecting NVE in compared areas. SS-OCTA was able to confirm absence of blood flow within the residual NV plexus when using VRS protocol in 30 eyes in which regression of NV with absence of leakage was documented on FFA. Three segmentation protocols (VRS, OVS and CVS) with different but complementary characteristics, allowed a reproducible and standardised investigation of NVD and NVE. The proposed new SS-OCTA cortical vitreous segmentation protocols may be of value when identifying and assessing NV-activity (VRS, OVS and CVS) or NV-regression (VRS) in PDR and therefore, response to therapy.


Marriage Markets and Intermarriage: Exchange in First Marriages and Remarriages.
Drawing on data from the American Community Survey, we compare patterns of assortative mating in first marriages, remarriages, and mixed-order marriages. We identify a number of ascribed and achieved characteristics that are viewed as resources available for exchange, both as complements and substitutes. We apply conditional logit models to show how patterns of assortative mating among never-married and previously married persons are subject to local marriage market opportunities and constraints. The results reveal that previously married individuals "cast a wider net": spousal pairings are more heterogamous among remarriages than among first marriages. Marital heterogamy, however, is reflected in systematic evidence of trade-offs showing that marriage order (i.e., status of being never-married) is a valued trait for exchange. Never-married persons are better positioned than previously married persons to marry more attractive marital partners, variously measured (e.g., highly educated partners). Previously married persons-especially women-are disadvantaged in the marriage market, facing demographic shortages of potential partners to marry. Marriage market constraints take demographic expression in low remarriage rates and in heterogamous patterns of mate selection in which previously married partners often substitute other valued characteristics in marriage with never-married persons.


Activation in ventral prefrontal cortex is sensitive to genetic vulnerability for attention-deficit hyperactivity disorder.
Attention-deficit hyperactivity disorder (ADHD) is a heritable neuropsychiatric disorder, associated with atypical patterns of brain activation in functional imaging studies. Neuroimaging measures may serve as an intermediate phenotype in genetic studies of ADHD, as they are putatively more closely linked to gene expression than a clinical diagnosis. We used rapid, mixed-trial, event-related functional magnetic resonance imaging (fMRI) to investigate changes in brain activation during a go no-go task in boys with ADHD, their unaffected siblings, and matched control subjects. On the hardest inhibitory trials in our task, children and adolescents with ADHD had lower accuracy than control subjects, whereas their unaffected siblings did not. Control subjects activated a network of regions, including ventral prefrontal and inferior parietal cortex. Both children and adolescents with ADHD and their unaffected siblings showed decreased activation in these areas, as well as fewer correlations between performance and activation. These findings suggest that the magnitude of activation during successful inhibitions is sensitive to genetic vulnerability for ADHD in a number of regions, including ventral prefrontal cortex. If this can be replicated in future studies, this suggests that neuroimaging measures related to inhibitory control may be suitable as intermediate phenotypes in studies investigating gene effects in ADHD.


Computer analysis of chromatin arrangement and nuclear texture in follicular thyroid tumours.
The differentiation of the thyroid glands follicular neoplasias into adenomas and carcinomas is currently done using the histological criteria recommended by WHO. This pilot study of 10 human follicular carcinomas and 10 folliculars adenomas demonstrates the possibility of a cytological classification using digital picture processing of high resolution cell images. Giemsa stained paraplast sections were scanned with a Colour-TV-camera, different channels were used with respect to staining and analyzing methods and computed with an image processing system. The computer aided cytophotometric methods detected significant differences in the chromatin arrangement and structure.


Improved agricultural Water management in data-scarce semi-arid watersheds: Value of integrating remotely sensed leaf area index in hydrological modeling.
In watersheds located in semi-arid regions, vegetation dynamics, evapotranspiration (ET), and associated water and energy balances collectively play a major role in controlling hydrological regimes and crop yield. As such, it is challenging to predict the complex hydrological processes and biophysical dynamics. This challenge increases in areas with limited data availability. The key objective of this study was to evaluate the direct integration of remotely sensed Leaf Area Index (LAI) data into a hydrological model to improve streamflow, ET, and crop yield estimates. We also demonstrated how an improved model integrated with remotely sensed LAI data can inform water managers by predicting water productivity (WP) under different irrigation schemes. We took agricultural-dominated San Joaquin Watershed in California, United States, as our testbed and integrated the Moderate Resolution Imaging Spectroradiometer (MODIS) 500-m resolution 4-day total LAI data into the SWAT (Soil and Water Assessment Tool) model. Results showed that, compared to conventional SWAT model that relies on semi-empirical equations and user inputs for simulating biophysical processes, direct LAI integration into SWAT model (SWAT-LAI) notably captured the actual vegetation dynamics and improved ET and crop yield estimations. The WP simulated by the improved SWAT-LAI model for almond and grape yields varied within a range from 0.363 to 3.81 kg/m3 and 0.32 to 4.76 kg/m3 across different irrigation applications. The outcomes of this study showed that deficit irrigation application could be a viable option in water stressed regions, since it can save a substantial amount of irrigation water and maintain the higher water productivity required for both almond and grape yield production. This study shows an evidence of how remotely sensed data integrated into hydrological models can serve as a decision support tool by providing quantitative information on crop water use and crop production.


CD73 expression in normal, hyperplastic, and neoplastic thyroid: a systematic evaluation revealing CD73 overexpression as a feature of papillary carcinomas.
CD73 converts AMP to adenosine, an immunosuppressive metabolite that promotes tumorigenesis. This study presents a systematic evaluation of CD73 expression in benign, hyperplastic, and neoplastic thyroid. CD73 expression was assessed by immunohistochemistry in 142 thyroid samples. CD73 was expressed in normal thyroid (3/6) and goiter (5/6), with an apical pattern and mild intensity. Apical and mild CD73 expression was also present in oncocytic cell adenomas/carcinomas (9/10; 5/8) and in follicular adenomas/carcinomas (12/18; 23/27). In contrast, papillary thyroid carcinomas featured extensive and intense CD73 staining (49/50) (vs. normal thyroid/goiter, p < 0.001). Seven of nine anaplastic carcinomas were CD73-positive with heterogeneous extensiveness of staining. Medullary and poorly differentiated carcinomas were mostly CD73-negative (1/6; 2/2). These results were corroborated by NT5E mRNA profiling. Papillary carcinomas feature enhanced CD73 protein and mRNA expression with distinct and intense staining, more pronounced in the invasive fronts of the tumors.


Association between tuberculosis in men and social network structure in Kampala, Uganda.
Globally, tuberculosis disease (TB) is more common among males than females. Recent research proposes that differences in social mixing by sex could alter infection patterns in TB. We examine evidence for two mechanisms by which social-mixing could increase men's contact rates with TB cases. First, men could be positioned in social networks such that they contact more people or social groups. Second, preferential mixing by sex could prime men to have more exposure to TB cases. We compared the networks of male and female TB cases and healthy matched controls living in Kampala, Uganda. Specifically, we estimated their positions in social networks (network distance to TB cases, degree, betweenness, and closeness) and assortativity patterns (mixing with adult men, women, and children inside and outside the household). The observed network consisted of 11,840 individuals. There were few differences in estimates of node position by sex. We found distinct mixing patterns by sex and TB disease status including that TB cases have proportionally more adult male contacts and fewer contacts with children. This analysis used a network approach to study how social mixing patterns are associated with TB disease. Understanding these mechanisms may have implications for designing targeted intervention strategies in high-burden populations.


Damage Control Laparotomy: High-Volume Centers Display Similar Mortality Rates Despite Differences in Country Income Level.
Comprehensive analysis of trauma care between high-, middle-, and low-income countries (HIC/MIC/LIC) is needed to improve global health. Comparison of HIC and MIC outcomes after damage control laparotomy (DCL) for patients is unknown. We evaluated DCL utilization among patients treated at high-volume trauma centers in the USA and South Africa, an MIC, hypothesizing similar mortality outcomes despite differences in resources and setting. Post hoc analysis of prospectively collected trauma databases from participating centers was performed. Injury severity, physiologic, operative data and post-operative outcomes were abstracted. Univariate and multivariable analyses were performed to assess differences between HIC/MIC for the primary outcome of mortality. There were 967 HIC and 602 MIC patients who underwent laparotomy. DCL occurred in 144 MIC patients (25%) and 241 HIC (24%) patients. Most sustained (58%) penetrating trauma with higher rates in the MIC compared to the HIC (71 vs. 32%, p = 0.001). Between groups, no differences were found for admission physiology, coagulopathy, or markers of shock except for increased presence of hypotension among patients in the HIC. Crystalloid infusion volumes were greater among MIC patients, and MIC patients received fewer blood products than those in the HIC. Overall mortality was 30% with similar rates between groups (29 in HIC vs. 33% in MIC, p = 0.4). On regression, base excess and penetrating injury were independent predictors of mortality but not patient residential status. Use and survival of DCL for patients with severe abdominal trauma was similar between trauma centers in HIC and MIC settings despite increased penetrating trauma and less transfusion in the MIC center. While the results overall suggest no gap in care for patients requiring DCL in this MIC, it highlights improvements that can be made in damage control resuscitation.


Transoral Outlet Reduction to Tackle Weight Regain After Roux-en-Y Gastric Bypass: a Single Center Initial Experience.
Long-term failure after Roux-en-Y gastric bypass (RYGB) is well known and occurs in 10-15% of patients according to the literature. Causes are multifactorial and dilatation of the gastro-jejunal anastomosis (GJA) is only one of these. A transoral outlet reduction (TORe) with endoscopic sutures to reinstall more restriction could be a valid and safe alternative to reduce regained weight after failed gastric bypass surgery. The objective of this article is to describe our single-center experience and discuss the adverse events of the technique. To describe our single-center case series and adverse events after TORe for weight regain after RYGB. We report a case series of 20 patients referred due to weight regain after RYGB with a dilated GJA. TORe was performed using an endoscopic full-thickness suture device (Apollo OverStitch®) to reduce the diameter of the GJA and the volume of the gastric reservoir. Prospectively collected data on technical feasibility, safety and efficacy are described with a median follow-up of 22 (6-38) months. Mean BMI was 44.5 kg/m2 at the time of RYGB. Postoperative nadir BMI was 27,7 kg/m2. The average time to TORe was 12.1 years after initial RYGB. Patients regained a mean 45.9% of excess body weight loss (EWL) before TORe and had a mean preprocedural BMI of 35.3 kg/m2. The aim was to reduce the aperture of the GJA to 5 mm which was done with a mean of 1.7 sutures and 3.5 stitches. The mean absolute weight loss was 13 kg and BMI reduction was 3.9 kg/m2 after 6 months. After a median follow-up of 22 months, a BMI of 31.4 kg/m2 was observed. Dumping symptoms resolved in four of our patients 6 weeks after TORe. Procedural adverse events were nausea and vomiting, sore throat, mild transient abdominal pain, diarrhea and constipation. All of them were treated conservatively. Due to a lack of weight loss, a suture failure was assumed in two of our patients. We describe one case of postprocedural mediastinitis, presumably due to a distal esophageal perforation, treated with a laparoscopic drainage without clinical evidence for perforation. Endoscopic TORe by narrowing the dilated GJA appears to be an efficient and safe minimal invasive option to tackle weight regain after RYGB and should be more used in clinical practice.


Fracture of the lateral malleolus with associated tear of the medical collateral ligament of the ankle.
A case of a fracture of the lateral malleolus with a missed diagnosis of associated tear of the deltoid ligament of the ankle is presented to emphasize the importance of examination of injuries about the ankle. The method of examination for this injury is described so that proper treatment may be undertaken.


Systematic Differences Between Total and Free Prostate-Specific Antigen Immunoassays: Comparison Using Passing and Bablok Regression.
Recent studies have shown that there are systematic differences among total and free prostate-specificantigen (PSA) immunoassays. In this study we analyzedintermethod differences in total PSA (tPSA) and free PSA(fPSA) measurement using ARCHITECT i2000SR (Abbott Diagnostics) and COBAS E601 (Roche Diagnostics). A number of 160 blood samples were tested for tPSA and 50 samples for fPSA (selecting only sampleswith tPSA: 4.1-10.0 μg/L). Passing-Bablok regression analysis was used to compare the two analytical methods fortPSA, fPSA and percentage of fPSA (%fPSA). A strong correlation was noticed between ARCHITECT i2000SR and COBAS E601 for tPSA, fPSA and %fPSA (r between 0.94 and 0.99). Concentrations of tPSA and fPSA measured by COBAS E601 were higher thanthose measured by ARCHITECT i2000SR with a bias of 0.8 μg/L for tPSA and 0.14 μg/L for fPSA. Analyzing therelative difference between methods for fPSA and %fPSA, COBAS E601 exceed a 10% relative difference limit. Our study confirms that there are differences in measured concentrations of tPSA and fPSA byvarious commercial methods. Because clinical judgment on subsequent diagnostic procedures, such as prostatebiopsy, is based on tPSA and fPSA results, tests harmonization should be a priority.


Parametric maps of spatial two-tissue compartment model for prostate dynamic contrast enhanced MRI - comparison with the standard Tofts model in the diagnosis of prostate cancer.
The spatial two-tissue compartment model (2TCM) was used to analyze prostate dynamic contrast enhanced (DCE) MRI data and compared with the standard Tofts model. A total of 29 patients with biopsy-confirmed prostate cancer were included in this IRB-approved study. MRI data were acquired on a Philips Achieva 3T-TX scanner. After T2-weighted and diffusion-weighted imaging, DCE data using 3D T1-FFE mDIXON sequence were acquired pre- and post-contrast media injection (0.1 mmol/kg Multihance) for 60 dynamic scans with temporal resolution of 8.3 s/image. The 2TCM has one fast (K 1 trans and k 1 ep ) and one slow (K 2 trans and k 2 ep ) exchanging compartment, compared with the standard Tofts model parameters (K trans and k ep ). On average, prostate cancer had significantly higher values (p < 0.007) than normal prostate tissue for all calculated parameters. There was a strong correlation (r = 0.94, p < 0.0001) between K trans and K 1 trans for cancer, but weak correlation (r = 0.28, p < 0.05) between k ep and k 1 ep . Average root-mean-square error (RMSE) in fits from the 2TCM was significantly smaller (p < 0.001) than the RMSE in fits from the Tofts model. Receiver operating characteristic (ROC) analysis showed that fast K 1 trans had the highest area under the curve (AUC) than any other individual parameter. The combined four parameters from the 2TCM had a considerably higher AUC value than the combined two parameters from the Tofts model. The 2TCM may be useful for quantitative analysis of prostate DCE-MRI data and may provide new information in the diagnosis of prostate cancer.


Surface color spectrophotometry in a murine model of steatosis: an accurate technique with potential applicability in liver procurement.
Steatosis is the most important prognostic histologic feature in the setting of liver procurement. The currently utilized diagnostic methods, including gross evaluation and frozen section examination, have important shortcomings. Novel techniques that offer advantages over the current tools could be of significant practical utility. The aim of this study is to evaluate the accuracy of surface color spectrophotometry in the quantitative assessment of steatosis in a murine model of fatty liver. C57BL/6 mice were divided into a control group receiving normal chow (n = 19), and two steatosis groups receiving high-fat diets for up to 20 weeks-mild steatosis (n = 10) and moderate-to-severe steatosis (n = 19). Mouse liver surfaces were scanned with a hand-held spectrophotometer (CM-600D; Konica-Minolta, Osaka, Japan). Spectral reflectance data and color space values (L*a*b*, XYZ, L*c*h*, RBG, and CMYK) were correlated with histopathologic steatosis evaluation by visual estimate, digital image analysis (DIA), as well as biochemical tissue triglyceride measurement. Spectral reflectance and most color space values were very strongly correlated with histologic assessment of total steatosis, with the best predictor being % reflectance at 700 nm (r = 0.91 [0.88-0.94] for visual assessment, r = 0.92 [0.88-0.95] for DIA of H&E slides, r = 0.92 [0.87-0.95] for DIA of oil-red-O stains, and r = 0.78 [0.63-0.87] for biochemical tissue triglyceride measurement, p < 0.0001 for all). Several spectrophotometric parameters were also independently predictive of large droplet steatosis. In conclusion, hepatic steatosis can accurately be assessed using a portable, commercially available hand-held spectrophotometer device. If similarly accurate in human livers, this technique could be utilized as a point-of-care tool for the quantitation of steatosis, which may be especially valuable in assessing livers during deceased donor organ procurement.


Morpho-physiological and transcriptome profiling reveal novel zinc deficiency-responsive genes in rice.
Intensive farming has depleted the soil zinc (Zn) availability resulting in decreased crop productivity. Here, we attempt to understand the Zn deficiency response in rice through temporal transcriptome analysis. For this, rice seedlings were raised under Zn-deficient conditions up to 4 weeks followed by Zn re-supply for 3 days. Zn-deficient plants developed characteristic deficiency symptoms such as leaf bronzing, decrease in biomass, total chlorophyll, PSII efficiency, decreased carbonic anhydrase activity and increased ROS production. Interestingly, severe alterations in root system architecture were also observed. Comprehensive transcriptome analyses of rice seedlings were carried out after 2 (DEF2W) and 4 weeks (DEF4W) of Zn deficiency with respect to transcriptome profiles of corresponding Zn sufficient conditions (SUF2W, SUF4W). Additionally, to detect the potential Zn-responsive genes, transcriptome profile of Zn-recovered seedlings was compared with DEF4W. All differentially expressed Zn-responsive genes were categorized into early and late Zn deficiency response, and a set of 77 genes, induced and repressed on Zn deficiency and re-supply, respectively, was identified. These genes could be used as low Zn-responsive marker genes. Further, genes involved in membrane transport, phytosiderophore activity and organic acid biosynthesis showed high differential expression. Additionally, the present study unravelled several genes putatively associated with alterations in root system architecture under Zn deficiency and provides novel insights into the interpretation of morpho-physiological, biochemical and molecular regulation of zinc deficiency responses in rice.


A Trifolium repens flavodoxin-like quinone reductase 1 (TrFQR1) improves plant adaptability to high temperature associated with oxidative homeostasis and lipids remodeling.
Maintenance of stable mitochondrial respiratory chains could enhance adaptability to high temperature, but the potential mechanism was not elucidated clearly in plants. In this study, we identified and isolated a TrFQR1 gene encoding the flavodoxin-like quinone reductase 1 (TrFQR1) located in mitochondria of leguminous white clover (Trifolium repens). Phylogenetic analysis indicated that amino acid sequences of FQR1 in various plant species showed a high degree of similarities. Ectopic expression of TrFQR1 protected yeast (Saccharomyces cerevisiae) from heat damage and toxic levels of benzoquinone, phenanthraquinone and hydroquinone. Transgenic Arabidopsis thaliana and white clover overexpressing TrFQR1 exhibited significantly lower oxidative damage and better photosynthetic capacity and growth than wild-type in response to high-temperature stress, whereas AtFQR1-RNAi A. thaliana showed more severe oxidative damage and growth retardation under heat stress. TrFQR1-transgenic white clover also maintained better respiratory electron transport chain than wild-type plants, as manifested by significantly higher mitochondrial complex II and III activities, alternative oxidase activity, NAD(P)H content, and coenzyme Q10 content in response to heat stress. In addition, overexpression of TrFQR1 enhanced the accumulation of lipids including phosphatidylglycerol, monogalactosyl diacylglycerol, sulfoquinovosyl diacylglycerol and cardiolipin as important compositions of bilayers involved in dynamic membrane assembly in mitochondria or chloroplasts positively associated with heat tolerance. TrFQR1-transgenic white clover also exhibited higher lipids saturation level and phosphatidylcholine:phosphatidylethanolamine ratio, which could be beneficial to membrane stability and integrity during a prolonged period of heat stress. The current study proves that TrFQR1 is essential for heat tolerance associated with mitochondrial respiratory chain, cellular reactive oxygen species homeostasis, and lipids remodeling in plants. TrFQR1 could be selected as a key candidate marker gene to screen heat-tolerant genotypes or develop heat-tolerant crops via molecular-based breeding.


Selecting suitable seed sludge for anammox enrichment: Role of influent characteristics and reactor operational conditions.
The study investigated the suitability of three different sludge collected from diverse environments for anammox process establishment. Sludge was collected from SBR (S1) treating municipal wastewater, nitrification tank (S2), denitrification tank (S3) treating fertilizer industrial wastewater. The microbial community in the seed sludge was studied. The presence of anammox bacteria was detected only in seed sludge S2 treating high NH4+-N wastewater. Seed sludge S3 showed high abundance of denitrifiers due to NO3--N and organic carbon rich environments in denitrification tank. The anammox start-up performances of sludge were assessed. S2 achieved start-up within 65 days whereas S1 and S3 showed longer start-up period of 79 and 93 days, respectively. S1, S2, S3 achieved nitrogen removal rate of 148.84 gN m-3day-1, 159.70 gNm-3day-1 and 120.90 gNm-3day-1, respectively. Influent NH4+-N, NO3--N and organic carbon concentrations governed the abundance of anammox and denitrifying bacteria in seed sludge thereby impacting the anammox start-up.


The use of cluster analysis for cell typing.
In invertebrates, large neurons, identifiable in each animal, have proven to be useful models for investigating basic neurobiological phenomena. In vertebrates, the number of neurons and the complexity of nervous systems increase and 'identifiability' is lost. To compensate for this, other approaches must be adopted to study the vertebrate brain. One successful approach has been to identify cell types, recognizable in each individual. The identification of cell types in central nuclei has helped us understand the organization of these nuclei and has provided an important foundation for examining possible relationships between the structure and function of neurons. Unfortunately, not all nuclei are composed of neurons of readily identifiable types. Nuclei lacking distinct cell types are, in general, less well understood than nuclei with morphologically distinct cell types. This article describes a statistical approach known as cluster analysis that we used to define cell types in the nucleus of the solitary tract-a nucleus that had been suggested to contain identifiable cell types but within which cell typing had proven difficult. Similar techniques have been used to classify Golgi-impregnated cells in the ventrobasal complex of the dog, the subthalamic nucleus of the bushbaby and the human retina. Cluster analysis has also been used in the gustatory system, in general, and nucleus of the solitary tract, in specific, to classify electrophysiologically characterized cells. The method also includes a technique for verifying the utility of the resulting classification.


Foreign Body Reaction Requiring Re-Exploration After Tympanoplasty With Porcine Small Intestinal Submucosa Reconstruction.
We present the first published case of large foreign body reaction to Biodesign (Cook Medical, Bloomington, IN), an acellular otologic graft matrix derived from porcine small intestinal submucosa, after use in tympanoplasty surgery in a patient without previous exposure to meat products. A single case report of a 39-year-old female who developed tinnitus, ear drainage, and large fibrotic mass in external auditory canal and extending into middle ear after Type I medial graft tympanoplasty with Biodesign Graft. Left endoscopic microdissection and resection of the tympanic membrane and middle ear fibrotic mass were performed. Surgical excision of the fibrous mass required extensive microdissection to ensure preservation of the ossicles and chorda tympani. Postoperatively, hearing improved and otalgia and otorrhea resolved. We report the first case of post-tympanoplasty reaction with the use of Biodesign acellular porcine graft in a patient with no previous known exposure to meat products. Although this presentation appears to be rare, it reinforces the need for careful patient selection and counseling around the use of porcine or other foreign grafts.


Prediction of pyrolyzate yields by response surface methodology: A case study of cellulose and polyethylene co-pyrolysis.
There are numerous combinations of biomass, plastic, and co-pyrolysis conditions. The presence of synergies, which make pyrolyzate distribution more complex, has been supported by research. In this study, the potential of response surface methodology (RSM) to predict the pyrolyzate yields affected by synergies during co-pyrolysis (500-700 °C) of cellulose and polyethylene was investigated, beyond gas, oil, and char yields. The results indicated that co-pyrolysis promoted liquid and C5-28 hydrocarbon production with increasing temperature. The quadratic model could predict the total gas, CO, CO2, and liquid yields, including the synergy. The cubic model could predict the levoglucosan and C5-28 hydrocarbon yields due to various synergies under different conditions. The linear model was suitable for the char yield distribution without interaction. Thus, this study reveals that RSM has a significant potential to predict pyrolyzate yields, enabling co-pyrolysis condition setting to maximize the desired product recovery with the fewest experiments.


Modified snodgrass hypospadias repair using the lembert suturing technique.
Surgical repair of hypospadias deformity is a challenging and complex issue. However, the technique of Snodgrass and its modifications attend promising functional and cosmetic results. To assess the Lembert suturing technique effectiveness as a modification of the Snodgrass technique in lowering an urethrocutanous fistula rate. Fifty boys with mid-shaft and distal hypospadias were repaired using the modified Snodgrass technique utilizing the interrupted Lembert suturing technique in neourethroplasty. Patients with previous failed operations or severe chordee were excluded from the study. None of the patients develops UCF apart from one who developed complete wound dehiscence following severe wound infection. Mild meatal stenosis is seen in two patients, and one patient experienced a small area of superficial skin sloughing.


Plicatic acid-specific IgE and nonspecific bronchial hyperresponsiveness in western red-cedar workers.
In a cross-sectional survey of 652 workers in a western red-cedar sawmill, we obtained data on symptoms, pulmonary function, immediate skin reactivity to common allergens, nonspecific bronchial responsiveness, total IgE level, and sensitization to plicatic acid conjugated with human serum albumin as measured by RAST. Dust exposure was estimated by personal and area sampling for total dust during a work shift and cumulative exposure by duration of employment. Seven percent of the workers had an elevated RAST, and 20% had nonspecific bronchial hyperresponsiveness. Elevation in RAST was associated with bronchial hyperresponsiveness. Almost half (46%) of the workers with RAST elevation had bronchial hyperresponsiveness compared to 18% in workers with no RAST elevation. The association was unaffected by total IgE level or by limiting the analysis to workers without respiratory symptoms and was most apparent in younger workers. Bronchial hyperresponsiveness was associated with increased prevalence of respiratory symptoms as well as with lower levels of pulmonary function. The likelihood of bronchial hyperresponsiveness increased with increasing age but was unrelated to the dust-exposure concentration. RAST elevation was unrelated to employment duration or dust exposure and was not associated with an increased prevalence of symptoms or lower levels of pulmonary function independent of bronchial hyperresponsiveness. We conclude that plicatic acid-specific IgE and nonspecific bronchial hyperresponsiveness are associated in western red-cedar workers and that this association may reflect a causal connection.


Factor XIII activity at onset of labour and association with postpartum haemorrhage: an exploratory post-hoc study.
Platelets, fibrinogen and factor XIII (FXIII) are required to form a stable clot in case of haemorrhage. The aims of this study were to evaluate a possible association between FXIII activity at the onset of labour and postpartum haemorrhage (PPH), and to ascertain whether FXIII activity at labour onset differs from after delivery. FXIII activity in 239 women with PPH (blood loss >1 L) and in 76 women without PPH was compared, as was activity before and after delivery in a third group of 80 women. FXIII activity at onset of labour was significantly lower in the PPH group compared with the control group (mean ± SD 0.98 ± 0.20 vs 1.05 ± 0.17 kIU/L; P=0.0006). The difference was significantly greater in subgroups having vaginal delivery with no oxytocin stimulation or uterine exploration (absolute difference 0.131; 95% CI 0.055 to 0.206), compared with a subgroup experiencing any complication (0.04; 95% CI -0.023 to 0.104; interaction P-value 0.098). There was a weak but statistically significant inverse correlation between FXIII and estimated blood loss (r=-0.25; P=0.030) in the control group but not the PPH group. There was no significant difference between FXIII activity at onset of labour and after delivery (mean ± SD 1.03 ± 0.17 vs 1.04 ± 0.19 kIU/L; P=0.093). At the onset of labour women with a subsequent PPH had significantly lower mean FXIII activity than that of women without PPH. This difference was small and within normal limits. FXIII activity did not change during normal delivery. The importance of FXIII during PPH requires study.


Effect of SARS-CoV-2 Vaccination on Symptoms from Post-Acute Sequelae of COVID-19: Results from the Nationwide VAXILONG Study.
Few data are available concerning the effect of SARS-CoV-2 vaccination on the persistent symptoms associated with COVID-19, also called long-COVID or post-acute sequelae of COVID-19 (PASC). We conducted a nationwide online study among adult patients with PASC as defined by symptoms persisting over 4 weeks following a confirmed or probable COVID-19, without any identified alternative diagnosis. Information concerning PASC symptoms, vaccine type and scheme and its effect on PASC symptoms were studied. 620 questionnaires were completed and 567 satisfied the inclusion criteria and were analyzed. The respondents' median age was 44 (IQR 25-75: 37-50) and 83.4% were women. The initial infection was proven in 365 patients (64%) and 5.1% had been hospitalized to receive oxygen. A total of 396 patients had received at least one injection of SARS-CoV-2 vaccine at the time of the survey, after a median of 357 (198-431) days following the initially-reported SARS-CoV-2 infection. Among the 380 patients who reported persistent symptoms at the time of SARS-CoV-2 vaccination, 201 (52.8%) reported a global effect on symptoms following the injection, corresponding to an improvement in 21.8% and a worsening in 31%. There were no differences based on the type of vaccine used. After a complete vaccination scheme, 93.3% (28/30) of initially seronegative patients reported a positive anti-SARS-CoV-2 IgG. A total of 170 PASC patients had not been vaccinated. The most common reasons for postponing the SARS-CoV-2 vaccine were fear of worsening PASC symptoms (55.9%) and the belief that vaccination was contraindicated because of PASC (15.6%). Our study suggests that SARS-CoV-2 vaccination is well tolerated in the majority of PASC patients and has good immunogenicity. Disseminating these reassuring data might prove crucial to increasing vaccine coverage in patients with PASC.


Puerperal lactation suppression and prolactin.
Five methods for puerperal lactation inhibition were assessed in a randomized fashion. The 90 women were divided into five groups. Four of these received a pharmacologic treatment: oral stilbestrol (15 mg dd for 5 days), a diuretic compound (bendroflumethazide 15 mg dd for 5 days) by mouth, oral bromocriptine (5 mg dd for 14 days), or an intramuscular injection containing estradiol (10 mg and testosterone (200 mg) esters administered immediately after delivery. To the women in the remaining group only physical methods were applied (breast support and local infra-red waves) and they served as controls. Prolactin plasma concentrations were determined daily for five consecutive days and showed a correlation with the clinical effectiveness of the various treatment schedules. While bromocriptine reduced and stilbestrol augmented prolactin levels, both types of treatment were equally effective in preventing lactation during the observation period. Treatment with a diuretic compound or with an injection of steroids, though less effective than the first two regimens, was nevertheless significantly more efficacious than physical treatment.


The hypothalamo-hypophysial system of the lamprey, Lampetra fluviatilis L. III. High-resolution radioautography of monoaminergic structures in neurohemal regions.
The distribution of monoaminergic structures was studied in the proximal neurosecretory contact region and neurohypophysis of the lamprey by light and electron microscopic radioautography. Only weak radioautographic reactions were found in the proximal neurosecretory contact region 1 h after injection of 3H-dopamine. High-resolution radioautography revealed some labeled neurosecretory terminals mainly in contact with the basement membrane of the connective tissue layer separating the proximal neurosecretory contact region from the hypophysial pars distalis. The number of silver grains as well as the number of neurosecretory terminals marked by the presence of labeled dopamine was much higher in the neurohypophysis of the same species. In the latter, labeled neurosecretory terminals were found in contact with the connective tissue layer containing blood vessels of the general circulation. Some neurosecretory terminals make synaptoid contacts with tanycyte perikarya and their basal processes. According to their ultrastructure and the size of their granules, the labeled neurosecretory terminals are identical with the B type terminals described in both neurohemal regions (transmission electron microscopy). No labeled neurosecretory terminals were observed in the proximal neurosecretory contact region and the neurohypophysis of lampreys treated with the serotonin precursor, 3H-5-hydroxytryptophan.


Detection of osteoclastic cell-cell fusion through retroviral vector packaging.
Cell-cell fusion generates multinucleated cells such as osteoclasts in bone, myotubes in muscle, and trophoblasts in placenta. Molecular details governing these fusion processes are still largely unknown. As a step toward identification of fusogenic genes, we tested the concept that retroviral vectors can be packaged as a result of cell-cell fusion. First, we introduced replication-deficient retroviral vectors expressing mCAT-1, which mediates fusogenic interaction with the retroviral envelope protein Env, into Chinese hamster ovary (CHO) cells to generate vector cells. Plasmids expressing virion proteins Gag, Pol, and Env were introduced into a separate culture of CHO cells to generate packaging cells. Co-culturing vector and packaging cells resulted in production of infectious retroviruses carrying the mCAT-1 gene as a consequence of cell-cell fusion. Second, we introduced a retroviral vector into primary osteoclast precursors and co-cultured them with established osteoclast precursor RAW264.7 cells, which turned out to harbor packaging activity. Packaged retroviral vector was detected in culture supernatants only where the osteoclast differentiation factor receptor activator for NF-kappaB ligand (RANKL) induced fusion between these two cell types. These data suggest that retrovirus production can occur as a result of cell-cell fusion. This provides a novel approach for isolating and characterizing fusogenic genes using retroviral expression vectors.


A new generation of MDR modulating agents with dual activity: P-gp inhibitor and iNOS inducer agents.
MultiDrug Resistance (MDR) is due to the ability of some ATPase transporters to efflux chemotherapeutic agents out from tumor cells decreasing the endocellular concentration for the pharmacological effect, causing cancer cells chemoresistance. In the present work, a set of MDR modulating agents (MC89, MC70, PB28, IG9) able to modulate transmembrane ATP-dependent transporter, P-glycoprotein (P-gp), and also to induce inducible nitric oxide synthase (iNOS) expression in a panel of tumor cell lines are presented. All selected compounds, known as potent P-gp modulating agents, stimulated nitric oxide (NO) via iNOS in U937, Caco-2 and MCF7-Adr cell lines. The results displayed a new pharmacological strategy to revert MDR and lead to develop a new class of MDR reverting agents devoid of the limits of P-gp inhibitors third generation.


Effect of Exogenous Zinc on MsrB1 Expression and Protein Oxidation in Human Lens Epithelial Cells.
Aging has been related to zinc deficiency, resulting in protein oxidation and age-related decline of methionine sulfoxide reductase (Msr) activity. This study was designed to investigate the levels of methionine sulfoxide reductase B1 (MsrB1) mRNA and oxidized proteins in human lens epithelial (hLE) cells after treatment with exogenous zinc. The role of exogenous zinc in regulation of MsrB1 gene expression and protein oxidation in hLE cells was studied by MTT assay, oxidized protein measurement kit, and real-time PCR. The results showed that hLE cell viability was significantly decreased by MsrB1 gene knockdown or peroxynitrite (ONOO-) treatment, while it was significantly increased after treatment with exogenous zinc (P < 0.05). Protein carbonyl content in hLE cell by MsrB1 gene knockdown or ONOO- treatment was significantly decreased after treatment with ZnSO4 (P < 0.01). And exogenous zinc could increase the level of MsrB1 in hLE cell under normal (P < 0.001) and oxidative stress (P < 0.01) conditions. In conclusion, exogenous zinc could protect hLE cells against MsrB1 gene knockdown or ONOO--induced cell death by upregulation of MsrB1 involved in the elimination of reactive oxygen species (ROS) and oxidized proteins.


[Positive and negative predictors of long-term results after an osteotomy around the knee joint].
A frequently asked question in the context of any surgical procedure, including an osteotomy around the knee joint, is "which parameters are in favor of a therapeutic success in this special case?" If the analysis of the leg geometry is in favor of an osteotomy, then the patient must be assessed further, taking into account the joint status and patient's condition. Positive outcome predictors for long-term success of an osteotomy around the knee, especially for a valgus osteotomy at the tibia are a tibial bone varus angle (TBVA) > 3-5°, knee joint range of motion > 100° flexion, male sex, and a BMI < 30. It is unclear whether the degree of degeneration of the affected (medial) compartment is of special relevance. The severity of malalignment, the patient's sex, and psychopathological comorbidities are not important.


Awareness and barriers to sustainability in dentistry: A scoping review.
(i) To undertake a comprehensive scoping review of the literature that addresses the research question 'What is the current state of environmental sustainability in general dental practice?' (ii) To provide an effective baseline of data that will consider general awareness, barriers and challenges for the implementation of sustainable practice. The scoping review was conducted for all published literature in the English language that addresses this topic up to the 31st April 2021. The method of the PRISMA-ScR (PRISMA extension for Scoping Reviews) was followed. 128 papers included in this scoping review consisted of: Commentary [Letters, editorials, communication and opinion] (n = 39); Research (n = 60); Literature reviews (n = 25); Reports [Policy and legislation] (n = 4). Each included record was analysed for emerging themes that were further classified according to their general relevance. The scoping review is considered over two manuscripts, with this first paper focusing on awareness of the problem and barriers or challenges to the implementation of sustainable care. Eight diverse but closely interlinked themes that influence the sustainability of oral health provision were identified: Environmental impacts (CO2e, air and water); Reduce, reuse, recycle and rethink; Policy and guidelines; Biomedical waste management; Plastics (SUPs); Procurement; Research & Education; Materials. Barriers to implementation were identified as: Lack of professional and public awareness; carbon emissions arising from patient and staff commute; challenges associated with the recovery and recycling of biomedical waste with a focus on SUPs; lack of knowledge and education into sustainable healthcare provision and; the challenges from the manufacturing, use and disposal of dental materials.


[Analysis of risk factors of relapse after allogeneic hematopoietic stem cell transplantation in patients with t (8;21) acute myeloid leukemia].
Objective: To investigate the risk factors of relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with t (8;21) acute myeloid leukemia (AML) . Methods: The clinical features of patients with t (8;21) AML who received allo-HSCT between January 2008 and October 2020 in the Hospital of Blood Disease and the Chinese Academy of Medical Sciences were retrospectively analyzed. Univariate and multivariate analyses were performed on the factors that might influence relapse. Results: A total of 73 patients were enrolled. The analysis revealed that, out of the 73 cases, 10 had relapses, with a 3-year cumulative incidence of relapse (CIR) of 15.7% (95% CI 7.3%-26.8%) . The median time of relapse was 9.2 (2.0-47.6) months. Furthermore, 19 cases died, with a 3-year overall survival (OS) of 68.9% (95% CI 56.4%-81.4%) . Compared with the RUNX1-RUNX1T1 at first diagnosis, a ≥ 3-log reduction within 3 months and/or 4-log reduction within 3-12 months can significantly decrease 3-year CIR after HSCT (13.3% vs 57.1%; 5.1% vs 25.0%, both P<0.001) . Cox multivariate analysis showed that high levels of RUNX1-RUNX1T1 (≥1.58%) on the day of transplantation (day 0) [P=0.006; HR=28.849 (95% CI 2.68-310.524) ] and the flow cytometric analysis of blasts ratio in bone marrow ≥60% at first diagnosis [P=0.015; HR=6.64 (95% CI 1.448-30.457) ] were independent risk factors for relapse. Furthermore, no significant difference in the effect of c-Kit and Flt3 gene mutations on relapse after transplantation was observed (P=0.877 and P=0.773, resp) . The flow cytometric analysis of blasts ratio in bone marrow ≥60% at first diagnosis [P<0.001; HR=8.925 (95% CI 2.702-29.476) ] and the number of courses to achieve complete remission ≥ 2[P=0.013; HR=4.495 (95% CI 1.379-14.649) ] were independent risk factors for OS. Conclusion: Both high levels of RUNX1-RUNX1T1 (≥1.58%) on the day of transplantation (day 0) and the ratio of flow cytometric analysis of blasts in bone marrow at first diagnosis increase the chance of t (8;21) AML relapse after allo-HSCT. Detection of the transcription levels of RUNX1-RUNX1T1 after allo-HSCT at different times could help predict the hazard of relapse.


Articular chondroprogenitors in platelet rich plasma for treatment of osteoarthritis and osteochondral defects in a rabbit knee model.
Articular chondroprogenitors are a promising contender for cartilage repair due to their inherent nature which stands primed for chondrogenesis and minimal hypertrophic preponderance. Platelet rich plasma (PRP) has been extensively used for treating cartilage defects and osteoarthritis (OA), due to its chondro-inductive properties and abundant pool of growth factors. The aim of this study was to assess the efficacy of chondroprogenitors injected with PRP versus PRP alone in the healing of experimentally created early OA and osteochondral defects (OCD) in a rabbit model. Adult New Zealand White male rabbits were used for cell and PRP isolation. Chondroprogenitors were isolated by fibronectin adhesion assay, labelled with iron oxide, characterized for surface markers, differential potential and expanded. PRP was isolated by double spin centrifugation using a TriCell kit. Study groups included (a) Monosodium iodoacetate induced early OA and (b) critical OCD. Following intervention (test arm: PRP+ chondroprogenitors and control arm: PRP), assessment was performed at 6- and 12-weeks which included histopathological examination and scoring (OARSI and Modified Wakitani score), immunohistochemistry analysis (Collagen type II and X) and synovial fluid S100A12 levels. Comparable, evident healing was noticed in both test and control arms when the OA group samples were assessed at both time points. In the OCD group, PRP alone exhibited significantly better results than the test arm, although repair was notable in both interventions. Further evaluation of chondroprogenitors is required to assess their role as a standalone therapy and in combination with PRP to further cartilage regeneration.


Emotional contagion: dogs and humans show a similar physiological response to human infant crying.
Humans respond to an infant crying with an increase in cortisol level and heightened alertness, a response interpreted as emotional contagion, a primitive form of empathy. Previous results are mixed when examining whether dogs might respond similarly to human distress. We examined whether domestic dogs, which have a long history of affiliation with humans, show signs of emotional contagion, testing canine (n=75) and human (n=74) responses to one of three auditory stimuli: a human infant crying, a human infant babbling, and computer-generated "white noise", with the latter two stimuli acting as controls. Cortisol levels in both humans and dogs increased significantly from baseline only after listening to crying. In addition, dogs showed a unique behavioral response to crying, combining submissiveness with alertness. These findings suggest that dogs experience emotional contagion in response to human infant crying and provide the first clear evidence of a primitive form of cross-species empathy.


Palpitations: a proper evaluation and approach to effective medical therapy.
Palpitations are a common complaint seen in the outpatient setting and the vast majority are benign, although they are occasionally a manifestation of potentially life-threatening conditions. We offer a step-wise guide to the evaluation and management of these patients with the primary goal to identify patients at highest risk for serious arrhythmias. We offer a brief overview of effective management of the varied causes of palpitations.


Aberrant TTF-1 expression in papillary high-grade urothelial neoplasm: case report and literature review.
We herein report the case of a 48-year-old man who developed synchronous advanced tumors in the lung and the bladder. The most striking feature of our case is that the otherwise typical bladder urothelial carcinoma showed focal areas (comprising less than 5% of the tumor mass) of nuclear positivity for TTF-1 (thyroid transcription factor-1). The different pattern of cytokeratin expression led us to consider them two independent primary tumors. Several recent reports have indicated that the type of clone used can influence the results of TTF-1 staining and can explain positivity in extrapulmonary and extrathyroid tumors.


Sexual dysfunction risk and associated factors in young Peruvian university women.
Information regarding sexual dysfunction risk among young Latin American women is limited. Assess female sexual dysfunction (FSD) risk and associated factors in young Peruvian university women. This was a nested case-control study, using the Female Sexual Function Index (FSFI). Cases were defined as women with total FSFI scores at or below 26.55 (increased FSD risk). Demographic characteristics, gynecologic aspects, body mass index, mood disorders, substance abuse, and issues related to the couple, were also evaluated. Primary end point was assessment of FSD risk and associated factors. A total of 625 women were surveyed of which 409 (65.4%) were sexually active. The average total FSFI score was 27.2 ± 4.3. Overall, 39.9% were at higher risk for FSD. Multivariate analysis using a binary logistic regression model found that male premature ejaculation (odds ratios [OR]=2.47, 95% confidence interval [CI]: 1.27-4.77), oral emergency contraception use (OR=1.87, 95% CI: 1.04-3.38), good partner relationship (OR=0.24, 95% CI: 0.12-0.49), and length of relationship (≥3 years; OR=0.025, 95% CI: 0.013-0.05) were factors independently associated to a higher FSD risk (goodness of fit P=0.39). In this young university female population, FSD risk was high and associated to male and female factors.


Granulocyte chemotactic protein-2 and related CXC chemokines: from gene regulation to receptor usage.
Chemokines contribute to the inflammatory response by selective attraction of various leukocytic cell types. Human GCP-2 was originally identified by amino acid sequence analysis as a CXC chemokine co-produced with IL-8 by osteosarcoma cells. Furthermore, the complete coding domain of human GCP-2 was disclosed by means of RT-PCR. Similarly, mouse GCP-2 was isolated from fibroblastoid and epithelial cells and completely identified by sequence analysis. Human and mouse GCP-2 share 61% identical amino acids. Both chemokines occur as multiple NH2-terminally truncated forms. The shorter forms of mouse, but not those of human, GCP-2 showed a higher neutrophil chemotactic potency and gelatinase B releasing capacity. Mouse GCP-2 was a more potent neutrophil activator than human GCP-2, natural mouse KC, and MIP-2. Human GCP-2 was not chemotactic for monocytes, lymphocytes, or eosinophils. Quantitative studies of mRNA expression in diploid fibroblasts revealed GCP-2 induction by IL-1beta. Human GCP-2 induced [Ca2+]i increase in neutrophils, which was reciprocally desensitized by IL-8, GROalpha, and ENA-78. Human GCP-2 induced [Ca2+]i increases and chemotactic responses in both CXCR1- and CXCR2-transfected cells. Finally, GCP-2 provoked neutrophil accumulation and plasma extravasation in rabbit skin. In humans, GCP-2 complements the activity of IL-8 as neutrophil chemoattractant and activator but it constitutes a major neutrophil chemokine in the mouse. GCP-2 induces neutrophil chemotaxis and activation but it might also contribute to detrimental tissue damage in sepsis, acute respiratory distress syndrome, acute hypersensitivity reactions, and autoimmune diseases. It might also influence the invasive capacity of GCP-2-secreting tumor cells.


Assessing the prognoses on Health care in the information society 2013--thirteen years after.
Health care and information technology in health care is advancing at tremendous speed. We analysed whether the prognoses by Haux et al. - first presented in 2000 and published in 2002 - have been fulfilled in 2013 and which might be the reasons for match or mismatch. Twenty international experts in biomedical and health informatics met in May 2013 in a workshop to discuss match or mismatch of each of the 71 prognoses. After this meeting a web-based survey among workshop participants took place. Thirty-three prognoses were assessed matching; they reflect e.g. that there is good progress in storing patient data electronically in health care institutions. Twenty-three prognoses were assessed mismatching; they reflect e.g. that telemedicine and home monitoring as well as electronic exchange of patient data between institutions is not established as widespread as expected. Fifteen prognoses were assessed neither matching nor mismatching. ICT tools have considerably influenced health care in the last decade, but in many cases not as far as it was expected by Haux et al. in 2002. In most cases this is not a matter of the availability of technical solutions but of organizational and ethical issues. We need innovative and modern information system architectures which support multiple use of data for patient care as well as for research and reporting and which are able to integrate data from home monitoring into a patient centered health record. Since innovative technology is available the efficient and wide-spread use in health care has to be enabled by systematic information management.


Expression of fibronectin in esophageal squamous cell carcinoma and its role in migration.
Fibronectin (FN) is a high-molecular-weight glycoprotein component of the extracellular matrix involved in cell adhesion, migration, metastasis, proliferation and differentiation, as well as embryogenesis, wound healing, and blood coagulation. Considerable recent research has established that tumor expression of FN is closely associated with tumor formation and development as well as disease prognosis. However, the mechanisms underlying this relationship have remained unclear. The aim of this study was to investigate FN protein expression in esophageal squamous cell carcinoma (ESCC) and determine its potential prognostic relevance, while also elucidating the source and function of FN. We conducted immunohistochemical analyses of protein expression in primary tumors of ESCC patients and analyzed their association with standard prognostic parameters and clinical outcomes. Expression of FN in two ESCC cell lines (Eca-109 and TE-1) was also examined by RT-PCR, immunofluorescence, and ELISA. ESCC cells were cultured in a microenvironment containing a high FN content, and changes in their morphology and migration ability were assessed by microscopy, wound-healing assays, and Transwell assays. FN expression in ESCC specimens was mainly detected in the tumor stroma, with very little FN detected in tumor cells. Stromal FN content in ESCC specimens was associated with lymphatic metastasis (P = 0.032) and prognosis. In this latter context, patients with high tumor stromal expression of FN showed worse overall survival (P = 0.002) and progression-free survival (P < 0.001) than those with low expression of FN. Interestingly, FN expression and secretion in ESCC cell lines (Eca-109 and TE-1) was found to be low, but these cells adopted a more migratory phenotype when cultured in vitro in a microenvironment containing high levels of FN. High FN expression in the stroma of ESCC tumors is closely associated with poor prognosis of patients. High stromal FN content facilitates tumor cell metastasis by promoting morphological changes and improving the motility and migratory ability of ESCC cells.


Affiliation of large numbers of fibroblasts with larval muscle fibers.
Muscle fibers from fourth and fifth instar caterpillars were examined with scanning and thin section electron microscopy. Scanning micrographs showed that early fifth instar specimens had a population of cells lying beneath the basal lamina over the surface of the muscle fiber and in conjunction with tracheoles and nerves. At least two cell types were present. One type could be categorized as tracheoblasts of their close association with the tracheoles and the presence of taenidia within the tracheoblast cytoplasm in sectioned material. A second cell type, characterized by long filamentous processes, contained extensive rough endoplasmic reticulum and cisternae swollen with an electron-dense substance similar in appearance to the basal lamina. This ultrastructural appearance is characteristic of vertebrate fibroblasts and certain types of insect hemocytes. Early and late fourth instar specimens had few cells on their muscle fiber surfaces. Measurements of the basal lamina thickness were taken from thin sections of nondigested muscle fibers of early fourth, late fourth, and early fifth instar animals. The results showed that the basal lamina underwent a large increase in thickness between the fourth and fifth instars. The proliferation of cells which appeared to be in an actively synthesizing state paralleled the increase in basal lamina thickness. This suggests the hypothesis that these cells are active in connective tissue formation, and contribute to the formation of the basal lamina that lies over both them and the muscle fiber.


Glass transition and enthalpy relaxation of amorphous lactose glass.
The glass transition temperature, T(g), and enthalpy relaxation of amorphous lactose glass were investigated by differential scanning calorimetry (DSC) for isothermal aging periods at various temperatures (25, 60, 75, and 90 degrees C) below T(g). Both T(g) and enthalpy relaxation were found to increase with increasing aging time and temperature. The enthalpy relaxation increased approximately exponentially with aging time at a temperature (90 degrees C) close to T(g) (102 degrees C). There was no significant change observed in the enthalpy relaxation around room temperature (25 degrees C) over an aging period of 1month. The Kohlrausch-Williams-Watts (KWW) model was able to fit the experimental enthalpy relaxation data well. The relaxation distribution parameter (beta) was determined to be in the range 0.81-0.89. The enthalpy relaxation time constant (tau) increased with decreasing aging temperature. The observed enthalpy relaxation data showed that molecular mobility in amorphous lactose glass was higher at temperatures closer to T(g). Lactose glass was stable for a long time at 25 degrees C. These findings should be helpful for improving the processing and storage stability of amorphous lactose and lactose containing food and pharmaceutical products.


Recurrent gynandroblastoma of the ovary with germline DICER1 mutation: A case report and review of the literature.
Sex cord-stromal tumors (SCSTs) are ovarian tumors that generally present with an adnexal mass and signs/symptoms of hormone excess. Gynandroblastoma is a rare subtype of SCST with a combination of female and male sex cord differentiation. These tumors typically present in premenopausal women and are diagnosed at early stages with benign clinical courses. Here, we present a rare case of recurrent gynandroblastoma in a premenopausal woman with a DICER1 germline mutation. The patient was referred to our clinic for new symptoms of hormonal imbalance with a history of ovarian juvenile granulosa cell tumor (JGCT). Evaluation revealed a 5x5cm complex right adnexal mass and rising inhibin B. Patient underwent total abdominal hysterectomy with right salpingo-oophorectomy, omentectomy and right pelvic and para-aortic lymphadenectomy. Pathology showed a right ovarian gynandroblastoma. Somatic biallelic mutations in the RNase IIIb domain of DICER1 were identified; a 23-gene germline panel confirmed a germline DICER1 pathogenic variant. Cascade testing of her children documented that both daughters inherited the pathogenic variant. Testing for DICER1 mutations has important implications for individual and familial tumor risk assessment given what we know about DICER1 mutation and increased childhood cancer risk.


Thermus thermophilus TMY isolated from silica scale taken from a geothermal power plant.
To identify an extreme thermophile, strain TMY, isolated from silica scale from the geothermal electric power plant and to examine microdiversity of Thermus thermophilus strains. The isolated strain TMY was identified by morphological, biochemical and physiological tests. Phylogenetic comparison of the strain and other Thermus strains with 16S rDNA analysis, RAPD and ERIC-PCR fingerprinting were performed. Strain TMY was closely related to strain which was isolated from a hot spring in New Zealand and shown to belong to the Japanese Thermus cluster. However, there were considerable genetic differences between strain TMY and other Thermus species using DNA fingerprinting. Based on morphological, physiological and genetic properties, strain TMY could be a strain of T. thermophilus. The distinct properties of strain TMY suggest that microdiversity of T. thermophilus strains should be considered. The results of this study have demonstrated genetic diversity within T. thermophilus strains, which were previously masked by an almost identical 16S rDNA sequence. RAPD and ERIC-PCR could be potential methods for distinguishing between Thermus strains.


Ectopic penile testis.
A case of a rare form of penile testicular ectopia is reported. The embryology is discussed, and ectopia is differentiated from cryptorchism.


Fuzzy oil drop model to interpret the structure of antifreeze proteins and their mutants.
Mutations in proteins introduce structural changes and influence biological activity: the specific effects depend on the location of the mutation. The simple method proposed in the present paper is based on a two-step model of in silico protein folding. The structure of the first intermediate is assumed to be determined solely by backbone conformation. The structure of the second one is assumed to be determined by the presence of a hydrophobic center. The comparable structural analysis of the set of mutants is performed to identify the mutant-induced structural changes. The changes of the hydrophobic core organization measured by the divergence entropy allows quantitative comparison estimating the relative structural changes upon mutation. The set of antifreeze proteins, which appeared to represent the hydrophobic core structure accordant with "fuzzy oil drop" model was selected for analysis.


Harmless disposal and resource utilization for secondary aluminum dross: A review.
Secondary aluminum dross (SAD) is solid waste of primary aluminum dross extracted aluminum, which contains approximately 40-60 wt% alumina, 10-30 wt% aluminum nitride (AlN), 5-15 wt% salts and other components. The salts include sodium chloride, potassium chloride and fluorine salts. SAD has dual attributes as resource and pollutant. SAD landfill disposal has the disadvantages of occupying land, wasting resources, a high cost and great environmental impact. SAD utilization methods are currently pyrometallurgy and hydrometallurgy. In pyrometallurgy, AlN is oxidized and the salts are evaporated at high temperature. After mixing, molding and calcination, firebricks and ceramics can be manufactured from SAD. In hydrometallurgy, AlN is hydrolyzed and salts are dissolved in water. After dissolving, filtrating, precipitating, washing and calcination, γ-Al2O3 can be prepared from SAD. Resource consumption and emission from both utilization methods were assessed. A ton of magnesium aluminum titanate based ceramics by pyrometallurgy consumes 1043 kg raw materials and releases 69 kg of waste gas, 4.17 t of waste water and no solid waste. A ton of γ-Al2O3 by hydrometallurgy consumes 3389 kg raw materials and releases 111 kg of waste gas, 12.98 t of waste water and 267 kg of solid waste. Therefore, the resource consumption and emission of SAD utilization by pyrometallurgy is lower than that by hydrometallurgy. We should focus on reducing the emission of the three wastes from pyrometallurgy. We are sure that SAD can be utilized for glass ceramics by pyrometallurgy. AlN and salts can be transformed into alumina and glass phases at high temperature with no emission. We should clarify mechanisms for SAD composition adjustment to lower the glass ceramics' melting point, AlN and salts transformed into alumina and glass phases respectively, and nucleation and crystal growth of glass ceramics at high temperature.


Pyrrolopyridazine MEK inhibitors.
The synthesis and SAR of a series of pyrrolopyridazine MEK inhibitors are reported. Optimal activity was achieved by incorporation of a 4-phenoxyaniline substituent at C4 and an acylated amine at C6.


Dataset regarding calcium bentonite and sodium bentonite as stabilizers for roads unbound.
The collected dataset derives from the laboratory testing of bentonite clay investigated as a stabilization technology for the unbound layers of road pavements. The effect of two kinds of bentonite (calcium based and sodium based) are assessed on two aggregate types commonly used as road construction materials. The investigation program, performed by means of repeated load triaxial tests, encompasses the different combinations of bentonite and aggregate types; two replicate specimens are tested dried for each condition. Considering the global need for ensuring well-performing road infrastructures while employing environmentally sound construction technologies, this dataset documenting the potential of bentonite clays used as road stabilizers can be of interest for several road stakeholders.


Exercise Intolerance in Heart Failure with Preserved Ejection Fraction.
Exercise intolerance represents a typical feature of heart failure with preserved ejection fraction (HFpEF), and is associated with a poor quality of life, frequent hospitalizations, and increased all-cause mortality. The cardiopulmonary exercise test is the best method to quantify exercise intolerance, and allows detection of the main mechanism responsible for the exercise limitation, influencing treatment and prognosis. Exercise training programs improve exercise tolerance in HFpEF. However, studies are needed to identify appropriate type and duration. This article discusses the pathophysiology of exercise limitation in HFpEF, describes methods of determining exercise tolerance class, and evaluates prognostic implications and potential therapeutic strategies.


Comment on "A photo-crosslinkable cartilage-derived extracellular matrix bioink for auricular cartilage tissue engineering" by Visscher et al.
STATEMENT OF SIGNIFICANCE: .


Impact of time and phosphorus application rate on phosphorus bioavailability and efficiency of secondary fertilizers recovered from municipal wastewater.
Demand for phosphorus (P) resources other than non-renewable P rock has driven the development of several P recovery technologies from municipal wastewater treatment and directed recovery of P into valuable fertilizers (struvite, ash, iron phosphate, etc.). Although the bioavailability of novel secondary P fertilizers has been examined in previous studies, insufficient attention has been paid to defining optimal plant growth duration and monitoring conditions to assess the dynamic changes in P. Accordingly, five fertilizers recovered from municipal wastewater: two struvites (STRSL and STRLQ), two ashes (ASH1 and ASH2), and iron-phosphate pelletized sludge (FeP) using triple superphosphate (TSP) as a positive control and blank (zero P) as a negative control, were applied to P poor-sand at three P doses (equivalent to 30, 60, and 90 kg P2O5 ha-1). Fertilizer impact on perennial ryegrass (Lolium perenne) dry matter (DM) and P concentration were evaluated on a monthly basis for seven months. DM and relative agronomical efficiency (RAE) have shown the same trend between the fertilizers, but only at the lowest P dose (corresponding to 30 kg P2O5 ha-1). At higher P doses (60, and 90 kg P2O5 ha-1) the differences in DM and RAE among the fertilizers diminished. STRLQ, STRSL, ASH1 and FeP expressed a rather steady P release pattern, while ASH2 had a delay of four cuts and increase afterward. Monitoring the P uptake during four months of perennial ryegrass growth turned out to be the minimum, and seven months the optimum period for reaching the full capacity of the slow-release P fertilizers.


A robust and efficient microvascular isolation method for multimodal characterization of the mouse brain vasculature.
Studying disease-related changes in the brain vasculature is warranted due to its crucial role in supplying oxygen and nutrients and removing waste and due to the anticipated vascular dysfunction in brain diseases. To this end, we have developed a protocol for fast and simple isolation of brain vascular fragments without the use of transgenic reporters. We used it to isolate and analyze 22,515 cells by single-cell RNA sequencing. The cells distributed into 23 distinct clusters corresponding to all known vascular and perivascular cell types in the brain. Western blot analysis also suggested that the protocol is suitable for proteomic analysis. We further adapted it for the establishment of primary cell cultures. The protocol generated highly reproducible results. In conclusion, we have developed a simple and robust brain vascular isolation protocol suitable for different experimental modalities, such as single-cell analyses, western blotting, and primary cell culture.


CD147 mediates the CD44s-dependent differentiation of myofibroblasts driven by transforming growth factor-β1.
Progressive fibrosis leads to loss of organ function and affects many organs as a result of excessive extracellular matrix production. The ubiquitous matrix polysaccharide hyaluronan (HA) is central to this through association with its primary receptor, CD44, which exists as standard CD44 (CD44s) or multiple splice variants. Mediators such as profibrotic transforming growth factor (TGF)-β1 and proinflammatory interleukin (IL)-1β are widely associated with fibrotic progression. TGF-β1 induces myofibroblast differentiation, while IL-1β induces a proinflammatory fibroblast phenotype that promotes fibroblast binding to monocyte/macrophages. CD44 expression is essential for both responses. Potential CD44 splice variants involved, however, are unidentified. The TGF-β1-activated CD44/epidermal growth factor receptor complex induces differentiation of metastatic cells through interactions with the matrix metalloproteinase inducer, CD147. This study aimed to determine the CD44 variants involved in TGF-β1- and IL-1β-mediated responses and to investigate the potential profibrotic role of CD147. Using immunocytochemistry and quantitative PCR, standard CD44s were shown to be essential for both TGF-β1-induced fibroblast/myofibroblast differentiation and IL-1β-induced monocyte binding. Co-immunoprecipitation identified that CD147 associated with CD44s. Using CD147-siRNA and confocal microscopy, we also determined that incorporation of the myofibroblast marker, αSMA, into F-actin stress fibers was prevented in the absence of CD147 and myofibroblast-dependent collagen gel contraction was inhibited. CD147 did not associate with HA, but removal of HA prevented the association of CD44s with CD147 at points of cell-cell contact. Taken together, our data suggest that CD44s/CD147 colocalization is essential in regulating the mechanical tension required for the αSMA incorporation into F-actin stress fibers that regulates myofibroblast phenotype.


Free radical generation, lipid peroxidation and essential fatty acids in patients with septicemia.
Infections due to gram-negative bacteria and other organisms can lead to septicemia and shock in some patients. Endotoxins, which cause these pathophysiological events, stimulate macrophages to elaborate tumor necrosis factor and other lymphokines. These lymphokines can augment free radical generation by polymorphonuclear leukocytes, macrophages and other cells, which may ultimately produce respiratory distress syndrome, multiorgan failure and irreversible shock seen in septicemia. This is supported by our results presented here that there is indeed an increase in free radical generation and lipid peroxidation in patients with septicemia. In addition, analysis of plasma lipid profile in these patients showed that gamma-linolenic, dihomogamma-linolenic and arachidonic acids of n-6 series and alpha-linolenic and eicosapentaenoic acids of the n-3 series are decreased in their plasma phospholipid fraction. These results suggest that free radicals, lipid peroxides, and alteration in essential fatty acid metabolism may have a role in the pathogenesis of septicemia.


A comparative clinical trial of diflunisal and ibuprofen in the control of pain in osteoarthritis.
A randomized double-blind study in ambulatory patients with osteoarthritis of hip and/or knee was conducted, comparing the efficacy and safety of diflunisal 500 mg daily with ibuprofen 1200 mg daily, and a period of 8 weeks. Thirty-five patients participated in the study. The results revealed no significant differences between the treatment groups with regard to the efficacy parameters.


QSAR, docking and in vitro studies for anti-inflammatory activity of cleomiscosin A methyl ether derivatives.
A series of five (6a-8b) novel polyhalogenated derivatives and an interesting ester (9a) derivative have been synthesized from cleomiscosin A methyl ether. All the six derivatives were subjected to in silico QSAR modeling and docking studies and later the predicted results were confirmed through in vitro experiments. QSAR modeling results showed that compounds 6a and 9a possessed anti-inflammatory activity comparable or even higher than diclofenac sodium. Docking results revealed that compounds 9a and 6a showed very good anti-inflammatory activity due to low docking energies of viz., IL6 (-92.45 and -81.993 kcal mol(-1)), TNF-α (-94.992 and -69.235 kcal mol(-1)) and IL1β (-67.462 and -65.985 kcal mol(-1)). Further all the six novel derivatives were subjected for in vitro anti-inflammatory activity using primary macrophages cell culture bioassay system. At the initial doses of 1 μg/ml and 10 μg/ml, the pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) were quantified from cell culture supernatant using enzyme linked immunosorbent assay (ELISA). The in vitro effect of 6a-9a on cell viability in mouse peritoneal macrophage cells isolated from mice was evaluated using MTT assay. The in silico and in vitro data suggested that all the derivatives might be considered as potential anti-inflammatory drug-like molecules.