Sialendoscopic Management of Obstructive Salivary Gland Pathology: A Retrospective Analysis of 236 Cases.
To analyze and assess the results of treating obstructive salivary gland pathology by sialendoscopy or sialendoscopic-assisted surgery and analyze the difference in submandibular and parotid gland pathology. Between December 2012 and March 2020, 211 patients (236 procedures) underwent sialendoscopy/sialendoscopic-assisted surgery for treatment of obstructive salivary gland pathology. The cases were retrospectively analyzed for type of pathology, symptomatic relief, type of intervention (endoscopy alone or combined with open surgery), recurrence of symptoms, number of gland excisions, and complications encountered. Sialolith cases (n = 117) were treated by sialendoscopic/sialendoscopy-assisted surgical sialolithotomy using basket or graspers. Strictures (n = 69) were treated by serial dilatation or balloon dilatation with or without intraductal steroid. Mucous plugs (n = 26) were managed by sialendoscopic lavage and occasional retrieval using wire baskets. There were 123 submandibular sialendoscopies in 118 patients and 113 parotid sialendoscopies in 95 patients. Of the 123 submandibular sialendoscopies, 99 were treated for sialolithiasis, 14 for strictures, 3 for mucous plugs, and 2 for foreign bodies. Of the 95 parotid sialendoscopies, 18 were treated for sialolithiasis, 55 for strictures, 23 for mucous plugs, and 1 for foreign body. The success rate was 85.3% for submandibular gland treatment and 92% for parotid gland treatment. About 62.7% of cases were treated by combined method (sialendoscopy with open approach) in submandibular gland and 50% in parotid gland. The number of gland excisions performed was 5 (2.1%). Sialendoscopy although associated with a gradual learning curve can be used for all cases of obstructive salivary gland pathology with excellent success rate and minimum morbidity. Parotid gland obstructive pathology is distinct from that seen in the submandibular gland, with strictures and mucous plugs contributing to most cases. Diagnosing and treatment planning for strictures and mucous plugs should therefore be as seamless as that for sialoliths.


A mathematical model for analyzing beat-to-beat difference in the human fetal heart rate during gestation and labor.
We devised a model suitable for mathematical analysis of beat-to-beat differences (BBDs) in fetal heart rates (FHRs). Factor analysis was applied, using a computer system, on a specially devised model of an FHR matrix. This matrix was arranged with FHRs and BBDs at 1-beat/min intervals by rows and columns, respectively. After obtaining the BBD by subtracting the antecedent FHR from the following FHR in a given pair of two consecutive FHRs, both variables of the antecedent FHR and BBD were crossed and the number of one was recorded at the corresponding element of the matrix. This procedure was done for all pairs of FHR and BBD yielding a matrix containing the cumulative incidences. Investigated was a total of 225,282 FHRs obtained from 20 fetuses between 37 and 41 weeks of gestation, by means of a scalp-lead electrocardiograph taken during labor. As shown by clusters of BBDs in units of beats/min, three different factors become evident: fluctuation around zero bpm, plus deviations and minus deviations. The first is considered to play a role in maintaining so-called baseline FHRs, and the second and the third indicate accelerating and decelerating actions on FHRs, respectively. This analytical model is discussed with reference to the findings obtained.


Quantitative cytochemistry of RNA in axotomized feline rubral neurons.
One-sided lateral funiculotomy at the C-2 segment induced axon reaction in the contralateral red nucleus of adult cats. Two to 60 days postoperatively the animals were sacrificed and the mesencephalon was fixed in ethanol-acetic acid, 3:1. Ten micrometer paraffin sections including both red nuclei were stained for RNA with azure B after incubation in DNAse. Cytophotometric measurements of RNA content of neurons from the caudal 600-1000 micrometer of each red nucleus were made with a Zeiss Cytoscan system using an automatic scanning stage. In contrast to the heightened RNA synthesis that has been reported for axotomized peripheral (extrinsic) neurons, the axotomized central (intrinsic) neurons of the red nucleus showed no evidence of accumulation of cytoplasmic or nucleolar RNA. Rather depletion of cellular RNA occurred. Further indication of the regressive nature of rubral axon reaction derived from morphometric measurements that showed cytoplasmic, nuclear and nucleolar atrophy of the neurons of the red nucleus contralateral to operation with the exception of a possible transient cytoplasmic enlargement 9 days postoperatively. From the cytophotometric and morphometric data here reported we are led to suggest that the frequently observed failure of axonal repair in mammalian CNS results from the innately regressive nature of the axon reaction of many mammalian central neurons.


Aspirin attenuates gentamicin ototoxicity: from the laboratory to the clinic.
This article reviews recent advances in the protection from the adverse auditory or vestibular side effects associated with antibacterial treatment with aminoglycoside antibiotics. Compelling evidence from animal models suggests that reactive oxygen species are part of the initial mechanisms that trigger apoptotic and necrotic cell death in the inner ear. Consequently, antioxidants protect against aminoglycoside-induced hearing loss in animals and, importantly, they do so without compromising drug serum levels or antibacterial efficacy. While clinical studies have long confirmed the ototoxicity of aminoglycosides in human, a trial on protection was only recently reported (Sha, S.-H., Qiu, J.-H., Schacht, J., 2006. Aspirin attenuates gentamicin-induced hearing loss. New Engl. J. Med. 354, 1856-1857). Based on the finding that salicylate afforded protection in animals, the efficacy of aspirin (acetyl salicylate) was tested in a randomized double-blind placebo-controlled study in patients receiving gentamicin for acute infections. Fourteen of 106 patients (13%) met the criterion of hearing loss in the placebo group while only 3/89 (3%) were affected in the aspirin group (p=0.013). Aspirin did not influence gentamicin serum levels or the course of therapy. These results indicate that therapeutic protection from aminoglycoside ototoxicity may be extrapolated from animal models to the clinic. Furthermore, medications as common as aspirin can significantly attenuate the risk of gentamicin-induced hearing loss.


Haemodynamic effects of intravenous bupivacaine during high thoracic epidural anaesthesia.
Administration of small doses of bupivacaine epidurally at the upper thoracic level will partially block the cardiac sympathetic nerves but not the sympathetic outflow via the adrenals. Local anaesthetics have direct systemic effects on the myocardium and the systemic circulation. The present study aimed to examine the effect of high thoracic epidural anaesthesia (TEA) in elderly patients, and to examine the effect of raising plasma bupivacaine concentrations in these patients, who had earlier had the sympathetic innervation of the heart blocked by thoracic epidural anaesthesia. Fifteen elderly patients scheduled for thoracotomy took part in the study. All received high thoracic epidural anaesthesia including the upper five thoracic dermatomes. When epidural block was established, ten patients received bupivacaine 3 mg/min intravenously for 20 min, while five patients received a corresponding volume of normal saline solution. After TEA was established, heart rate, mean arterial blood pressure and cardiac output decreased. When bupivacaine was given to these patients intravenously during the block, mean arterial blood pressure increased, while cardiac output decreased still more. The mechanisms behind these effects seem to be a direct constriction of the systemic blood vessels and a depressive effect on the myocardium, which was blocked from the influence of the cardiac sympathetic nerves by the high thoracic epidural block.


Dietary salt initiates redox signaling between endothelium and vascular smooth muscle through NADPH oxidase 4.
Prevention of phenotype switching of vascular smooth muscle cells is an important determinant of normal vascular physiology. Hydrogen peroxide (H2O2) promotes osteogenic differentiation of vascular smooth muscle cells through expression of Runt related transcription factor 2 (Runx2). In this study, an increase in dietary NaCl increased endothelial H2O2 generation through NOX4, a NAD(P)H oxidase. The production of H2O2 was sufficient to increase Runx2, osteopontin and osteocalcin in adjacent vascular smooth muscle cells from control littermate mice but was inhibited in mice lacking endothelial Nox4. A vascular smooth muscle cell culture model confirmed the direct involvement of the activation of protein kinase B (Akt) with inactivation of FoxO1 and FoxO3a observed in the control mice on the high NaCl diet. The present study also showed a reduction of catalase activity in aortas during high NaCl intake. The findings demonstrated an interesting cell-cell communication in the vascular wall that was initiated with H2O2 production by endothelium and was regulated by dietary NaCl intake. A better understanding of how dietary salt intake alters vascular biology may improve treatment of vascular disease that involves activation of Runx2.


[Incidence of hemagglutination-inhibiting antibodies in the population of Milan and of Bari against strains of influenza viruses of epidemiological importance in the winter of 1977-78].
A sero-epidemiological survey was carried out on 555 serum samples from normal subjects of both sexes (age: from few months to over 60 years) collected in the late summer 1977 in Milan and Bari, two towns with rather different climatic conditions. In both localities a further large spread of A/Victoria/3/75 strain seems unlikely, since 54% of sera from Milan and 58% of those from Bari have h.i.a. at protective titers. On the contrary, the degree of immunity against B/Hong Kong/8/73 virus is still faiitical level for the survival of A/Hong Kong/68 pandemic strain appears almost reached in the population of Milan, where 76% of subjects have antibody at protective titers. In Bari such percentage is 60%. The statistical analysis (X2 test) of the data concerning the subjects with h.i.a. at titers greater than or equal to 1:40 shows only one significant difference between Milan and Bari, that is the A/Hong Kong/68 antibody prevalence. Probably this is due to the low number of males of Bari with protective antibody levels.


Fatty Acid Composition and Contents of Seven Commercial Fish Species of Genus Coregonus from Russian Subarctic Water Bodies.
In several Russian northern lakes and rivers, Arctic cisco Coregonus autumnalis, least cisco C. sardinella, peled C. peled, tugun C. tugun, broad whitefish C. nasus, whitefish C. lavaretus and vendace C. albula were sampled in periods of officially permitted commercial fishery. Special attention was paid to contents (mg g-1 of wet weight) of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in muscle tissues (filets), which are essential for human nutrition. The highest values of EPA + DHA content in semi-anadromous fish and freshwater fish were recorded for C. autumnalis from the Yenisei River, 17.60 mg g-1 wet weight, and for C. lavaretus from the Sobachye Lake, 16.61 mg g-1 wet weight, respectively. Intra-genus variations of EPA + DHA contents of Coregonus species were from 1.87 to 17.60 mg g-1 wet weight. Since the congeneric species were genetically close to each other, the variations in EPA and DHA contents were thought to be caused primarily by ecological factors: migrational capability, type of feeding and trophic status of aquatic ecosystems. In general, the majority of studied species appeared to be of a high nutritive value for humans, although unfavorable environmental conditions could considerably diminish this value.


The Spider Limb Positioner in subscapular system free flaps.
The subscapular system is a versatile vascular network that can provide multiple flaps for reconstruction of the head and neck. A significant drawback of using the subscapular system is that patient positioning can preclude the use of simultaneous two-team ablative and reconstructive surgery. Herein, we describe a novel use of an upper extremity limb positioner (Spider Limb Positioner) used primarily in orthopedic surgery to facilitate concurrent two-team technique in head and neck surgery. Using a bean bag and the Spider Limb Positioner for the upper extremity, a semidecubitus position was used for subscapular donor site dissection. Ablative and reconstructive teams worked concurrently in all cases. This technique was utilized 78 times on 73 patients, with chimeric flaps used in 38% of cases. The average operative time was 466 min. Only one patient required repositioning intraoperatively due to a change in the subscapular donor site side. There were no nerve compression injuries or positioning related complications. Scapular and parascapular free flaps are useful tools for reconstruction of the head and neck. In a two-team approach, the use of a semidecubitus position in conjunction with the Spider Limb Positioner facilitates exposure for the reconstructive team without compromising access for the ablative team.


Virtual cells in a virtual microenvironment recapitulate early development-like patterns in human pluripotent stem cell colonies.
The mechanism by which morphogenetic signals engage the regulatory networks responsible for early embryonic tissue patterning is incompletely understood. Here, we developed a minimal gene regulatory network (GRN) model of human pluripotent stem cell (hPSC) lineage commitment and embedded it into "cellular" agents that respond to a dynamic morphogenetic signaling microenvironment. Simulations demonstrated that GRN wiring had significant non-intuitive effects on tissue pattern order, composition, and dynamics. Experimental perturbation of GRN connectivities supported model predictions and demonstrated the role of OCT4 as a master regulator of peri-gastrulation fates. Our so-called GARMEN strategy provides a multiscale computational platform to understand how single-cell-based regulatory interactions scale to tissue domains. This foundation provides new opportunities to simulate the impact of network motifs on normal and aberrant tissue development.


Gray and white matter abnormalities in primary trigeminal neuralgia with and without neurovascular compression.
Previous researches have reported gray and white matter microalterations in primary trigeminal neuralgia (TN) with neurovascular compression (NVC). The central mechanism underlying TN without NVC are unknown but may include changes in specific brain regions or circuitries. This study aimed to investigate abnormalities in the gray matter (GM) and white matter (WM) of the whole brain and the possible pathogenetic mechanism underlying this disease. We analyzed brain morphologic images of TN patients, 23 with NVC (TN wNVC) and 22 without NVC (TN wNVC) compared with 45 healthy controls (HC). All subjects underwent 3T-magnetic resonance imaging and pain scale evaluation. Voxel-based morphometry (VBM) and surface-based morphometry (SBM) were used to investigate whole brain grey matter quantitatively; graph theory was applied to obtain network measures based on extracted DTI data based on DTI data of the whole brains. Sensory and affective pain rating indices were assessed using the visual analog scale (VAS) and short-form McGill Pain Questionnaire (SF-MPQ). The VBM and SBM analyses revealed widespread decreases in GM volume and cortical thickness in TN wNVC compared to TN woNVC, and diffusion metrics measures and topology organization changes revealed DTI showed extensive WM integrity alterations. However, above structural changes differed between TN wNVC and TN woNVC, and were related to specific chronic pain modulation mechanism. Abnormalities in characteristic regions of GM and WM structural network were found in TN woNVC compared with TN wNVC group, suggesting differences in pathophysiology of two types of TN.


Transcriptome analysis reveals the mechanism of different fruit appearance between apricot (Armeniaca vulgaris Lam.) and its seedling.
Apricot fruit has great economic value. In the process of apricot breeding using traditional breeding methods, we obtained a larger seedling (named Us) from the original variety (named U). And Us fruit is larger than U, taste better. Therefore, revealing its mechanism is very important for Apricot breeding. In this study, de novo assembly and transcriptome sequencing (RNA-Seq) was used to screen the differently expressed genes (DEGs) between U and Us at three development stages, including young fruits stage, mid-ripening stage and mature fruit stage. The results showed that there were 6,753 DEGs at different sampling time. "Cellulose synthase (UDP-forming) activity" and "cellulose synthase activity" were the key GO terms enriched in GO, of which CESA and CSL family played a key role. "Photosynthesis-antenna proteins" and "Plant hormone signal transduction" were the candidate pathways and lhca, lhcb, Aux/IAA and SAUR were the main regulators. The auxin signaling pathway was active in Us, of which Aux/IAAs and SAUR were the key fruit size regulators. The low level of lhca and lhcb in Us could reveal the low demand for exogenous carbon, but they increased at mature stage, which might be due to the role of aux, who was keeping the fruit growing. Aux and photosynthesis maight be the main causes of appearance formation of Us fruits. Interestingly, the higher expression of CESA and CSL proved that Us entered the hardening process earlier than U. The advanced developmental progress might also be due to the role of Aux.


The Impact of SARS-CoV-2 on Stroke Epidemiology and Care: A Meta-Analysis.
Emerging data indicate an increased risk of cerebrovascular events with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and highlight the potential impact of coronavirus disease (COVID-19) on the management and outcomes of acute stroke. We conducted a systematic review and meta-analysis to evaluate the aforementioned considerations. We performed a meta-analysis of observational cohort studies reporting on the occurrence and/or outcomes of patients with cerebrovascular events in association with their SARS-CoV-2 infection status. We used a random-effects model. Summary estimates were reported as odds ratios (ORs) and corresponding 95% confidence intervals (CIs). We identified 18 cohort studies including 67,845 patients. Among patients with SARS-CoV-2, 1.3% (95% CI = 0.9-1.6%, I2 = 87%) were hospitalized for cerebrovascular events, 1.1% (95% CI = 0.8-1.3%, I2 = 85%) for ischemic stroke, and 0.2% (95% CI = 0.1-0.3%, I2 = 64%) for hemorrhagic stroke. Compared to noninfected contemporary or historical controls, patients with SARS-CoV-2 infection had increased odds of ischemic stroke (OR = 3.58, 95% CI = 1.43-8.92, I2 = 43%) and cryptogenic stroke (OR = 3.98, 95% CI = 1.62-9.77, I2 = 0%). Diabetes mellitus was found to be more prevalent among SARS-CoV-2 stroke patients compared to noninfected historical controls (OR = 1.39, 95% CI = 1.00-1.94, I2 = 0%). SARS-CoV-2 infection status was not associated with the likelihood of receiving intravenous thrombolysis (OR = 1.42, 95% CI = 0.65-3.10, I2 = 0%) or endovascular thrombectomy (OR = 0.78, 95% CI = 0.35-1.74, I2 = 0%) among hospitalized ischemic stroke patients during the COVID-19 pandemic. Odds of in-hospital mortality were higher among SARS-CoV-2 stroke patients compared to noninfected contemporary or historical stroke patients (OR = 5.60, 95% CI = 3.19-9.80, I2 = 45%). SARS-CoV-2 appears to be associated with an increased risk of ischemic stroke, and potentially cryptogenic stroke in particular. It may also be related to an increased mortality risk. ANN NEUROL 2021;89:380-388.


Utilizing Ubiquitination Patterns to Predict Prostate Cancer Prognosis and Devise a Therapeutic Response.
Ubiquitination, a post-translational modification, is crucial for cancer regulation. However, the predictive significance of ubiquitination-related genes (URGs) for prostate adenocarcinoma (PRAD) remains unclear. The objectives of the study were to investigate the role of URGs in PRAD and their potential impact on patient prognosis. This study acquired data for more than 800 patients with PRAD from public databases. The unique ubiquitination-related patterns of PRAD were detected by unsupervised clustering approach. URGs relevant to the prognosis of patients with PRAD and a ubiquitination-related prognostic index (URPI) were identified and generated using the log-rank test, univariate and multivariate Cox proportional hazards regression, least absolute shrinkage and selection operator (LASSO) Cox regression, and bootstrap strategy. Four ubiquitination-related subpopulations were then defined, and 39 ubiquitination-related differentially expressed genes in prostate cancer and paracancerous samples were screened, with LASSO analysis distinguishing six of them. The URPI was built and verified using the identified URGs that played critical roles in survival stratification. Several potential URPI-targeting drugs were also analyzed. Subsequently, the URPI was combined with clinical characteristics, which provided a more accurate estimate of PRAD survival and was a superior choice for PRAD prognostic forecasts. This investigation has thus established and verified a URPI, which may provide unique insights to improve survival estimations for patients with PRAD.


Effect of culture conditions on production of butter flavor compounds by Pediococcus pentosaceus and Lactobacillus acidophilus in semisolid maize-based cultures.
Two series of 120 h mixed cultures of Pediococcus pentosaceus MITJ-10 and Lactobacillus acidophilus Hansen 1748 were grown in semisolid maize-based media, applying an orthogonal factorial design in order to establish the most adequate parameters to get compounds related to butter-like flavor. Conditions of maize pre-treatment established in the first series were hot lime-treatment for 20 min, grinding and sieving to 0.0165 in., partial defatting and cooking for 25 min. While the culture conditions established for the second series were the addition of yeast extract (0.2% w/w), and culture starting with 2x10(6) CFU g(-1) and a ratio of P. pentosaceus and L. acidophilus, 3:1. The fermentation profile was studied in a last culture. Lactic acid bacteria (LAB) prevailed over the native microorganisms, with a specific growth rate of 0.47 h(-1). Diacetyl production correlated (r2=0.9972) with the 12 h exponential growth phase of LAB. The concentration of diacetyl at that time was 779.56 mg kg(-1). The contents of lactic acid and volatile fatty acids were low at 12 h, 665 and 1312 mg kg(-1), respectively. During the long stationary phase, they increased up to 4800 and 1886 mg kg(-1), respectively. This procedure might be useful to prepare naturally aromatized raw materials for the food industry.


Emerging role of TWEAK-Fn14 axis in lupus, a disease related to autoimmunity and fibrosis.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder. Lupus nephritis (LN) is one of the severe clinical implications in SLE, and this was relates to fibrosis in the kidney. As an important marker in the tumor necrosis factor (TNF) superfamily, TNF-like weak inducer of apoptosis (TWEAK) has been given much attention with respect to its role in regulating pro-inflammatory immune response. Fibroblast growth factor-inducible 14 (Fn14), the sole receptor for TWEAK, has been found expressed in different immune and non-immune cells. TWEAK binds to Fn14, and then regulates inflammatory components production via downstream signaling pathways. To date, dysregulated expression of TWEAK, Fn14 has been reported in SLE, LN patients, and in vivo, in vitro studies have discussed the significant role of TWEAK-Fn14 axis in SLE, LN pathogenesis, partly through mediating the fibrosis process. In this review, we will discuss the association of TWEAK-Fn14 axis in lupus. Understanding the relationship will better realize the potential for making TWEAK-Fn14 as a marker for the diseases, and will help to give many clues for targeting them in treatment of lupus in the future.


Management of severe osteoporosis.
Severe osteoporosis represents a disease of high mortality and morbidity. Recognition of what constitutes and causes severe osteoporosis and aggressive intervention with pharmacological agents with evidence to reduce fracture risk are outlined in this review. This review is a blend of evidence obtained from literature searches from PubMed and The National Library of Medicine (USA), clinical experience and the author's opinions. The review covers the recognition of what constitutes severe osteoporosis, and provides up-to-date references on this sub-set of high risk patients. Severe osteoporosis can be classified by using measurements of bone densitometry, identification of prevalent fractures, and, knowledge of what additional risk factors contribute to high fracture risk. Once recognized, the potential consequences of severe osteoporosis can be mitigated by appropriate selection of pharmacological therapies and modalities to reduce the risk for falling.


Geriatric trauma: demographics, injuries, and mortality.
To identify injuries that elderly sustain during high-energy trauma and determine which are associated with mortality. Retrospective review of prospectively collected database. Academic trauma center. Patients selected from database of all trauma admissions from January 2004 through June 2009. Study population consisted of patients directly admitted from scene of injury who sustained high-energy trauma with at least one orthopaedic injury and were 65 years or older (n = 597). Review of demographics, trauma markers, injuries, and disposition statuses. Statistical analysis using χ test, Student t test, and logistic regression analysis. The most common fractures were of the rib, distal radius, pelvic ring, facial bones, proximal humerus, clavicle, ankle, and sacrum. The injuries associated with the highest mortality rates were fractures of the cervical spine with neurological deficit (47%), at the C2 level (44%), and of the proximal femur (25%), pelvic ring (25%), clavicle (24%), and distal humerus (24%). The fractures significantly associated with mortality were fractures of the clavicle (P = 0.001), foot joints (P = 0.001), proximal humerus or shaft and head of the humerus (P = 0.002), sacroiliac joint (P = 0.004), and distal ulna (P = 0.002). Elderly patients present with significantly worse injuries, remain in the hospital longer, require greater use of resources after discharge, and die at 3 times the rate of the younger population. Although the high mortality rates associated with cervical spine, hip, and pelvic ring fractures were not unexpected, the injuries that were statistically associated with mortality were unexpected. Injuries such as clavicle fracture were statistically associated with mortality. As our population ages and becomes more active, the demographic may gain in clinical importance. Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.


Lipidic cubic phase crystal structure of the photosynthetic reaction centre from Rhodobacter sphaeroides at 2.35A resolution.
Well-ordered crystals of the bacterial photosynthetic reaction centre from Rhodobacter sphaeroides were grown from a lipidic cubic phase. Here, we report the type I crystal packing that results from this crystallisation medium, for which 3D crystals grow as stacked 2D crystals, and the reaction centre X-ray structure is refined to 2.35A resolution. In this crystal form, the location of the membrane bilayer could be assigned with confidence. A cardiolipin-binding site is found at the protein-protein interface within the membrane-spanning region, shedding light on the formation of crystal contacts within the membrane. A chloride-binding site was identified in the membrane-spanning region, which suggests a putative site for interaction with the light-harvesting complex I, the cytochrome bc(1) complex or PufX. Comparisons with the X-ray structures of this reaction centre deriving from detergent-based crystals are drawn, indicating that a slight compression occurs in this lipid-rich environment.


Combined effects of elevated CO2 and warmer temperature on limitations to photosynthesis and carbon sequestration in yellow birch.
Elevated CO2 and warmer temperature occur simultaneously under the current climate change. However, their combined effects on the photosynthetic traits in boreal trees are not well understood. This study investigated the morphological and photosynthetic responses of yellow birch (Betula alleghaniensis Britt.) to a combined treatment of CO2 and temperature (ambient, ACT (400 μmol mol-1 CO2 and current temperature) vs elevated, ECT (750 μmol mol-1 CO2 and current +4 °C temperature)). It was found that ECT significantly reduced leaf-area based photosynthetic rate (An), maximum Rubisco carboxylation rate (Vcmax), photosynthetic electron transport rate (Jmax), leaf nitrogen concentration, respiration and mesophyll conductance. There were two interesting findings: first, the primary mechanism of photosynthetic limitation shifted from Ribulose-1,5-bisphosphate (RuBP) carboxylation (related to Vcmax) to RuBP regeneration (related to Jmax) in response to ECT, leading to decreased transition point (Ci-t and An-t) from RuBP carboxylation to regeneration; second, the increase in total leaf area in response to ECT more than compensated for the downregulation of leaf-area based photosynthesis, leading to greater biomass in ECT than in ACT. We proposed a new protocol for evaluating photosynthetic limitations by comparing the relative relationship between the transition point (Ci-t and An-t) and the photosynthetic rate at growth CO2 (Ci-g and An-g). Furthermore, we found that Jmax (RuBP regeneration) was the primary limitation to An under ECT.


Bilateral nasal ala reconstruction of the cocaine-injured nose with 2 free reverse-flow helical rim flaps.
Cocaine abuse can lead to nasal deformity because of local ischemia and subsequent fibrosis. Reconstruction can be challenging. We present a case of bilateral microsurgical nasal ala reconstruction with 2 reverse-flow helical rim flap.


Canadian Society of Transplantation and Canadian Society of Nephrology Commentary on the 2017 KDIGO Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors.
To review an international guideline on the evaluation and care of living kidney donors and provide a commentary on the applicability of the recommendations to the Canadian donor population. We reviewed the 2017 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors and compared this guideline to the Canadian 2014 Kidney Paired Donation (KPD) Protocol for Participating Donors. A working group was formed consisting of members from the Canadian Society of Transplantation and the Canadian Society of Nephrology. Members were selected to have representation from across Canada and in various subspecialties related to living kidney donation, including nephrology, surgery, transplantation, pediatrics, and ethics. Many of the KDIGO Guideline recommendations align with the KPD Protocol recommendations. Canadian researchers have contributed to much of the evidence on donor evaluation and outcomes used to support the KDIGO Guideline recommendations. Certain outcomes and risk assessment tools have yet to be validated in the Canadian donor population. Living kidney donors should be counseled on the risks of postdonation outcomes given recent evidence, understanding the limitations of the literature with respect to its generalizability to the Canadian donor population.


Improved glucose electrochemical biosensor by appropriate immobilization of nano-ZnO.
We constructed the transferred ZnO biosensor and the grown ZnO biosensor by two different nano-ZnO immobilization approaches. And the influence of different assembly processes on the biosensor performance has been systematically investigated and compared. An enhanced sensitivity of the grown ZnO biosensor is found to be 52% higher than that of the transferred ZnO biosensor. Correspondingly, the other properties are also better in the grown ZnO biosensor, including the response time, the detection limit and the linear range. These results are well consistent with the fact that more glucose oxidase is immobilized on the well-aligned ZnO arrays, which have higher specific surface area and more direct electron communication path, in the grown sensor than the randomly distributed and stacked ZnO nanorods in the transferred sensor. The nano-ZnO grown directly has been demonstrated more desirable for enzymatic immobilization and signal transduction in the high performance biosensors.


Molecular events leading to fusiform morphological transformation by partial src deletion mutant of Rous sarcoma virus.
A mutant of the Prague strain of Rous sarcoma virus (RSV) has two deletions near the 5'-terminus of its src gene. The mutant (dl 5) induced fusiform morphological transformation in chick embryo fibroblasts (CEF) in contrast to the round type morphological transformation induced by wild type (wt) RSV. The partially deleted src of dl5 was shown to code for a 52K protein which has tyrosine kinase activity as high as that of p60src. In dl 5-transformed cells, a 36K protein was heavily phosphorylated, while two proteins (MW = 55K and 57K) were dephosphorylated to the same extent as compared with cells transformed by wt RSV. The relative abundance of phosphotyrosine in vinculin was almost the same in both dl 5- and wt RSV-transformed cells after extended passage of dl 5-transformed cells without marked changes in their morphology. On the other hand, the amounts of vinculin and fibronectin in dl 5-transformed cells were twice those in wt RSV-transformed cells, although less than the amounts in uninfected cells. These results suggest that events leading to cellular morphological transformation are neither directly correlated with phosphorylation of the 36K protein, with dephosphorylation of the 55K and 57K proteins, nor with the level of phosphorylation of tyrosine residues in vinculin, but rather are correlated with the amount of vinculin and fibronectin.


iNOS affects matrix production in distal lung fibroblasts from patients with mild asthma.
A high level of exhaled nitric oxide (NO) is a marker for inflammation in the airways of asthmatic subjects. However, little is known about how NO and inducible nitric oxides synthase (iNOS) activity may affect remodelling in the distal lung. We hypothesized that there is a link between iNOS and ongoing remodelling processes in the distal lung of mild asthmatics. Patients with mild asthma (n = 6) and healthy control subjects (n = 8) were included. Exhaled NO was measured at different flow rates and alveolar NO concentrations were calculated. For studies of remodelling processes in the distal lung, primary fibroblasts were grown from transbronchial biopsies and stimulated with unselective and selective NOS inhibitors or a NO donor. The mRNA expression of iNOS and synthesis of NO (indirectly as nitrite/nitrate) were measured and distal lung fibroblast synthesis of the extracellular matrix proteoglycans were analysed. The distal lung fibroblasts expressed iNOS, and there was a tendency of higher expression in fibroblasts from patients with asthma. The selective iNOS inhibitor 1400 W inhibited iNOS expression and NO synthesis in fibroblasts from patients with asthma (p = 0.031). Treatment with 1400 W significantly increased synthesis of the proteoglycan versican (p = 0.018) in distal fibroblasts from patients with asthma whereas there were no effects in fibroblasts from control subjects. Our data suggest that there is a link between iNOS and remodelling in the distal lung of subjects with mild asthma and that iNOS could have a modulatory role in pathological airway remodelling.


OA in 2011: Age-related OA--a concept emerging from infancy?
That primary osteoarthritis (OA) is an age-related disorder is undoubted, but how aging contributes to OA is poorly understood. New insights from 2011 offer potential explanations, novel models for study, and the suggestion that a deeper understanding of what 'aging' actually is might pave the way to everlasting joints.


Subcutaneous granuloma annulare: MR imaging and literature review.
Subcutaneous granuloma annulare (SGA) is little known to radiologists. Better knowledge of this lesion may prompt accurate diagnosis. A typical case is presented with plain radiography, ultrasound and MR imaging, and is confirmed by histology. When an otherwise healthy child presents with a rapidly growing, solitary, nontender, subcutaneous soft tissue mass, located on the scalp or extensor aspect of the limbs, that radiologically presents as an indistinct radiodense and hypoechoic mass, isointense to muscle on T1- and slightly hypointense to fat on T2-weighted MR images, without calcifications, bone involvement or extracompartmental invasion, SGA should be suspected.


Health services reform in Bangladesh: hearing the views of health workers and their professional bodies.
In Bangladesh, widespread dissatisfaction with government health services did not improve during the Health and Population Sector Programme (HPSP) reforms from 1998-2003. A 2003 national household survey documented public and health service users' views and experience. Attitudes and behaviour of health workers are central to quality of health services. To investigate whether the views of health workers influenced the reforms, we surveyed local health workers and held evidence-based discussions with local service managers and professional bodies. Some 1866 government health workers in facilities serving the household survey clusters completed a questionnaire about their views, experience, and problems as workers. Field teams discussed the findings from the household and health workers' surveys with local health service managers in five upazilas (administrative sub-districts) and with the Bangladesh Medical Association (BMA) and Bangladesh Nurses Association (BNA). Nearly one half of the health workers (45%) reported difficulties fulfilling their duties, especially doctors, women, and younger workers. They cited inadequate supplies and infrastructure, bad behaviour of patients, and administrative problems. Many, especially doctors (74%), considered they were badly treated as employees. Nearly all said lack of medicines in government facilities was due to inadequate supply, not improved during the HPSP. Two thirds of doctors and nurses complained of bad behaviour of patients. A quarter of respondents thought quality of service had improved as a result of the HPSP.Local service managers and the BMA and BNA accepted patients had negative views and experiences, blaming inadequate resources, high patient loads, and patients' unrealistic expectations. They said doctors and nurses were demotivated by poor working conditions, unfair treatment, and lack of career progression; private and unqualified practitioners sought to please patients instead of giving medically appropriate care. The BMA considered it would be dangerous to attempt to train and register unqualified practitioners. The continuing dissatisfaction of health workers may have undermined the effectiveness of the HPSP. Presenting the views of the public and service users to health managers helped to focus discussions about quality of services. It is important to involve health workers in health services reforms.


Single fraction of accelerated partial breast irradiation in the elderly: early clinical outcome.
To analyze the clinical outcome of elderly women with early breast cancer who underwent accelerated partial breast irradiation (APBI) based on a post-operative single fraction of multicatheter interstitial high dose-rate brachytherapy (MIB). A single institution retrospective cohort study was performed focusing on elderly patients (≥ 65 years old) presenting a low-risk breast carcinoma treated by lumpectomy plus axillary evaluation followed by MIB. A single fraction of 16 Gy was prescribed on the 100% isodose. Clinical outcome at 3 years was reported based on local relapse free survival (3-y LRFS), specific survival (SS) and overall survival (OS). Acute (< 180 days after APBI) and late toxicity were evaluated. Cosmetic results were clinically evaluated by the physician. Between January 2012 and August 2015, 48 women (51 lesions) were treated. Median age was 77.7 years (range: 65-92) with a median tumor size of 12 mm (range: 3-32). Five patients (pts) presented an axillary lymph node involvement (4 Nmic, 1 N1). Invasive ductal carcinoma was the most frequent histology type (86.3%). With a median follow-up of 40 months (range: 36-42), no local relapse occurred while 1 pt. developed axillary relapse (2.1%). The 3-y LRFS, SS and OS rates were 100%, 100% and 93.1% respectively. Forty-five acute events were remained. The most frequent acute toxicity was grade (G) 1 hyperpigmentation (26.7%), 3 pts. (6.3%) presented G3 acute toxicity (2 breast hematomas, 1 breast abscess). No ≥ G3 late toxicity was observed while 15 late toxicities occurred (G1: 13 events - 86.7%) mainly breast fibrosis). The rate of excellent cosmetic outcome was 76.4%. We reported promising and encouraging clinical outcome of a post-operative single fraction of MIB ABPI in the elderly. This approach leads to consider a sfAPBI as an attractive alternative to intra-operative radiation therapy while all the patients will be good candidates for APBI in regards to the post-operative pathological report. More mature results (number of patients and follow-up) are needed.


The Clinical Characteristics of Pediatric Non-Infectious Uveitis in Two Tertiary Referral Centers in Turkey.
Purpose: To report the manifestations, patterns of disease, treatment strategies and outcomes in pediatric patients with noninfectious uveitis.Methods: Demographic information of 76 cases was recorded. Symptoms, anatomic location, laterality, visual acuity (VA), intraocular pressure, associated systemic diseases, therapeutic strategies, side effects, complications were reviewed.Results: Thirty-one patients were diagnosed as uveitis on routine surveillance because of underlying systemic disease. The most common anatomic location was intermediate uveitis (34.2%). Juvenile idiopathic arthritis (JIA) was the most common underlying systemic disease (25%). Glaucoma was the most common complication (7.7%). The patients with refractory uveitis received adalimumab (26.5%), infliximab (4.6%) and tocilizumab (3.1%). The mean first-year VA was between 20/32 and 20/20 in 116/140 eyes.Conclusion: Most pediatric noninfectious uveitis cases have bilateral intermediate uveitis. JIA was the most common systemic association. The first-year VA was good in most eyes which may be due to early use of corticosteroid-sparing agents.


Growth of copper indium diselenide ternary thin films (CuInSe2) for solar cells: Optimization of electrodeposition potential and pH parameters.
Herein, copper indium diselenide ternary (CuInSe2) thin film has been deposited on Indium Tin Oxide (ITO) coated glass substrate by electrochemical deposition technique with different potential and pH solutions. CuInSe2 thin films were deposited by one-step electrodeposition before post-depot selenization at 450 °C for 30 min. The effect of potential and pH on the structural and optical properties of CuInSe thin film have been studied using X-ray diffraction (XRD), Scanning electron microscopy (SEM), and UV-Visible spectrometer. According to the X-ray diffraction (XRD) measurements, it was observed that all samples exhibit prominent reflections (112), (204/220), and (312/116) of tetragonal CuInSe2. The films electrodeposited at -0.8 V potential shows growth and peak values increasing in the (204/220) crystal direction within a pH range of 2.2, whereas the films electrodeposited at pH 2.6 tend to favor an increase in (112) peaks. We also noticed an improvement in surface morphology and adherent of CuInSe2 thin films electrodeposited at -0.8 V applied potential from the solution having pH 2.6. The band gaps of samples electrodeposited at -0.8V potentials from pH 2.6, 2.4, and 2.2 solutions were 1.15 eV, 1.25 eV, and 1.21 eV, respectively. As part of our investigation, we used a Solar Cell capacitance simulator (SCAPS) to perform our electrodeposited films. The most effective Power conversion efficiency (PCE) was obtained for thin films electrodeposited at -0.8 V within the solution having pH 2.4.


Office hysteroscopic-guided selective tubal chromopertubation: acceptability, feasibility and diagnostic accuracy of this new diagnostic non-invasive technique in infertile women.
The aim of this study was to evaluate accuracy, tolerability and side effects of office hysteroscopic-guided chromoperturbations in infertile women without anaesthesia. Forty-nine infertile women underwent the procedure to evaluate tubal patency and the uterine cavity. Women with unilateral or bilateral tubal stenosis at hysteroscopy with chromoperturbation, and women with bilateral tubal patency who did not conceive during the period of six months, underwent laparoscopy with chromoperturbation. The results obtained from hysteroscopy and laparoscopy in the assessment of tubal patency were compared. Sensitivity, specificity, accuracy, positive-predictive value and negative-predictive value were used to describe diagnostic performance. Pain and tolerance were assessed during procedure using a visual analogue scale (VAS). Side effects or late complications and pregnancy rate were also recorded three and six months after the procedure. The specificity was 87.8% (95% CI: 73.80-95.90), sensitivity was 85.7% (95% CI 57.20-98.20), positive and negative predictive values were 70.6% (95% CI: 44.00-89) and 94.7% (95% CI: 82.30-99.40), respectively. Pregnancy rate (PR) within six months after performance of hysteroscopy with chromoperturbation was 27%. Office hysteroscopy-guided selective chromoperturbation in infertile patients is a valid technique to evaluate tubal patency and uterine cavity.


Clinic and Home Blood Pressure Lowering Effect of an Angiotensin Receptor Blocker, Fimasartan, in Postmenopausal Women with Hypertension.
Angiotensin receptor blockers may be an appropriate first-line agent for postmenopausal women with hypertension because the activation of renin-angiotensin-aldosterone system is suggested as one possible mechanism of postmenopausal hypertension. However, there are few studies substantiating this effect. This study aimed to investigate clinic and home blood pressure (BP) lowering effect of fimasartan, a new angiotensin receptor blocker, in postmenopausal women with hypertension.Among patients with hypertension enrolled in K-Mets Study, 1373 women with fimasartan as a first antihypertensive drug and 3-months follow-up data were selected. They were divided into 2 groups; premenopausal women (pre-MPW; n = 382, 45.3 ± 4.6 years) and postmenopausal women (post-MPW; n = 991, 60.9 ± 8.2 years).Baseline clinic systolic BP was not different (pre-MPW; 152.9 ± 15.2 vs. post-MPW; 152.8 ± 13.5 mm Hg), but diastolic BP was lower in post-MPW (pre-MPW; 95.7 ± 9.4 vs. post-MPW; 91.9 ± 9.4 mm Hg, P <0.001). After 3-month treatment, clinic BP declined effectively without significant differences between 2 groups (Δsystolic/diastolic BP: pre-MPW; -25.7 ± 17.7/-14.2 ± 11.3 vs. post-MPW; -25.7 ± 16.3/-13.1 ± 10.9 mm Hg). Home morning and evening systolic BP decreased similarly in both groups (Δmorning/evening systolic BP: pre-MPW; -21.3 ± 17.9/-23.1 ± 15.8 vs. post-MPW; -20.4 ± 17.3/-20.2 ± 19.2 mm Hg). Fimasartan also significantly decreased the standard deviations of home morning and evening systolic BP of pre-MPW and post-MPW.Fimasartan was a similarly effective BP lowering agent in both post-MPW and pre-MPW with hypertension, and it also decreased day-to-day BP variability.


Proximity hybridization induced rolling circle amplification for label-free SERS detection of the depression marker human apolipoprotein A4.
A new label-free method was developed for SERS detection of human apolipoprotein A4. Rolling circle amplification (RCA) was used, which could induce the production of AuNPs (poly adenine and adsorption gold nanoparticles). When there were two DNA labeled antibodies and target protein, MB1 (molecular beacon 1) was unfolded and the substrate was modified in the homogeneous solution, and the proximate complex was formed. The unfolded molecular beacon worked as a primer in the hybridization with the RCA template to start RCA, which could produce many long sequences of DNA containing amounts of adenines. The AuNPs were bound with the long-repeated adenine in the RCA product, causing accumulation of AuNPs on the surface of the electrode. It was indicated that the spectral characteristics of adenine at 736 cm-1 strongly dominated the SERS spectrum of DNA. Adenine worked as an internal marker for detecting human apolipoprotein A4 by using label-free SERS method. When the conditions were optimal, the detection of human apolipoprotein A4 was carried out from 10 pg mL-1 to 1000 ng mL-1, and the detection limit was low (4.1 pg mL-1). Meanwhile, the specificity was also excellent because the antibody could specifically bind with the corresponding antigen. In addition, since adenine was dominant in SERS spectra and the affinity between AuNPs and poly adenine was high, the detection procedure could be performed without any sophisticated modification. This method might provide a promising strategy for diagnosis in clinical practice.


In situ photosynthetic differentiation of the green algal and the cyanobacterial photobiont in the crustose lichen Placopsis contortuplicata.
In situ photosynthetic activity in the green algal and the cyanobacterial photobionts of Placopsis contortuplicata was monitored within the same thallus using chlorophyll a fluorescence methods. It proved possible to show that the response to hydration of the green algal and the cyanobacterial photobionts is different within the same thallus. Measurements of the photochemical efficiency of PS II, Fv/Fm, reveal that in the dry lichen thallus photosynthetic activity could be induced in the green algal photobiont by water vapour uptake, in the cyanobacterial photobiont only if it was hydrated with liquid water. However, rates of apparent electron flow through PS II as well as rates of CO2 gas exchange were suboptimal after hydration with water vapour alone and maximum rates could only be observed when the thallus was saturated with liquid water. The differences in the waterrelated photosynthetic performance and different light response curves of apparent electron transport rate through PS II indicate that the two photobionts act highly independently of each other. It was shown that the cyanobacteria from the cephalodia in P. contortuplicata act as photobiont. The rate of electron flow through PS II was found to be saturated at 1500 μmol photon m-2 s-1, despite a considerable increase of non-photochemical quenching in the green algal photobiont which is lacking in the cyanobacterial photobiont. No evidence of photoinhibition could be found in either photobiont. Pronounced competition between the green algal and the cyanobacterial thallus can be observed in the natural habitat, indicating that the symbiosis in P. contortuplicata should be regarded as a very variable adaptation to the extreme environmental conditions in the maritime Antarctic.


Endovascular thrombectomy in octogenarians and nonagenarians with large vessel occlusion: Technical aspects and clinical outcome.
Safety and efficacy of thrombectomy in patients ≥80-year-old is not fully understood as this age group is underrepresented in major clinical trials. To review the procedural aspects and clinical outcome of thrombectomy among octogenarians and nonagenarians in a busy comprehensive stroke center. We retrospectively identified all patients ≥80-year-old who underwent thrombectomy for acute ischemic stroke with emergent large vessel occlusion (ELVO) in the anterior circulation in our institution. Demographics, procedural variables, anesthesia modality, and clinical outcome measures were extracted. The rates of successful recanalization (defined as TICI ≥ 2B), symptomatic hemorrhagic transformation and favorable clinical outcome (defined as mRS<3 at 90 days) were identified. A total of 113 patients were identified. The median age for the cohort was 85 years (range: 80-103). Median admission NIHSS score was 18 (IQR: 14-25). Successful recanalization was achieved in 101 patients (89%). Monitored anesthesia care (MAC) was used in 78% of the patients. Groin puncture to recanalization time was shorter in patients under MAC (45±36 vs 120±50; p=0.006); however, no statistically significant difference in the rate of 90-day favorable outcome was observed between MAC and general anesthesia(23% vs 20%, p=0.77). From 72 patients with baseline mRS<3, 22% had a favorable 90-day outcome. Thrombectomy in octogenarians and nonagenarians is technically feasible and associated with high rate of recanalization. Anesthesia type was not a predictor of outcome and does not pose a threat on procedural time. Nearly one out of four patients in this study had a favorable clinical outcome.


The efficacy of drug-eluting bead or conventional transarterial chemoembolization plus apatinib for hepatocellular carcinoma with portal vein tumor thrombus.
Transarterial chemoembolization (TACE) combined with apatinib has been used for advanced hepatocellular carcinoma (HCC), and the efficacy is good. The study was conducted to compare the efficacy and safety of drug-eluting bead TACE plus apatinib (D-TACE-A) with conventional TACE plus apatinib (C-TACE-A) in the treatment of HCC with portal vein tumor thrombus (PVTT). A total of 130 continuous patients who received D-TACE-A or C-TACE-A were included in the study from January 2017 to June 2020. Propensity score matching (PSM) was used to reduce potential selection bias. Before PSM, the median overall survival (mOS) (14 months) and median progression-free survival (mPFS) (7 months) in the C-TACE-A group were longer than the mOS (9 months; P = 0.001) and mPFS (4 months; P = 0.001) in the D-TACE-A group. After PSM, the mOS (14 months vs 9 months; P = 0.039) and mPFS (7 months vs 5 months; P = 0.009) in the C-TACE-A group were longer than those in the D-TACE-A group. In the multivariate regression analysis, C-TACE-A reduced the mortality rate and tumor progression rate compared with D-TACE-A. For the subgroup analysis, patients with VP1-2, without extrahepatic metastases, and with multiple TACE sessions who received C-TACE-A had a lower death risk and tumor progression risk than patients who received D-TACE-A. Before PSM, there was no statistically significant difference in any grade or grade III/IV adverse events (all P > 0.05). C-TACE-A could prolong mOS and mPFS in patients with PVTT, especially for patients with VP1-2 stage PVTT, no extrahepatic tumor metastases, and multiple TACE sessions.


Effect of initial developmental stage on morphology of transplanted embryonic chick pancreas.
It has been reported that only certain types of pancreatic parenchymal cells survive transplantation. This study examines whether the extent of differentiation of the pancreas at the time of transplantation affects the resulting morphology or viability of its components. Segments of chick pancreas or its primordia from stages preceding formation of dorsal bud (60 h) through hatching (day 21) were implanted in the abdominal region of three-day chick embryos. After various periods of growth, grafts were examined by light- and electron microscopy. In all transplants, individual endocrine cells (A, B, D, PP) and islet structure were identical to those of normal embryos of comparable age. The exocrine portion also appeared normal in implants from embryos younger than seven days. In grafts from older donors, however, normal acini and ducts were replaced by dilated, irregularly shaped tubules from which new islets appeared to develop. These results suggest that transplantation causes structural modification of exocrine tissue, which may reflect its initial functional capabilities. These observations are compared with similar structural alterations that occur following experimental obstruction of ducts and in human pancreatic pathology.


Design of an embedded PID controller applied to blood pressure control.
Some diseases, such as hypertension, require a close control of the patient's blood pressure. This is even more critical when that patient is going through--or has just underwent--a surgical procedure In such situations, reducing blood pressure to normal levels is of paramount importance. Usually, this demanding and time consuming monitoring is done manually by clinical personnel and are subject to mistakes and inconsistent practices. In this paper, we propose a solution to the manual monitoring through the design and implementation of an embedded PID controller to handle blood pressure, integrated to an automated monitoring system to assist in detecting anomalies and to optimize the process of patient care.


Intraluminal papillary carcinoma of the gallbladder: prognostic value of computed tomography and sonography.
Twenty-seven consecutive cases with a prospective diagnosis of cancer of the gallbladder were analyzed to clarify the computed tomographic (CT) and ultrasonographic features, behavior, and prognosis of intraluminal papillary carcinoma (n = 7) of the organ. With CT and ultrasonography, these intraluminal carcinomas were further classified into 3 subtypes: single polyp, multiple polyp, and jam-packed gallbladder. Preoperative diagnosis, evaluation of local invasiveness, and detection of metastatic lesions were reliably done. Carcinomas of this type were locally less invasive, less frequently metastasized, and resulted in a longer survival than the other massive and thickened-wall carcinomas.


Thirty-day mortality in UK patients with community-onset and hospital-acquired meticillin-susceptible Staphylococcus aureus bacteraemia.
The difference in mortality between patients with community-onset and hospital-acquired Staphylococcus aureus infections has rarely been described and where it has, results have been conflicting. To determine 30-day mortality in consecutive patients with meticillin-susceptible Staphylococcus aureus (MSSA) bacteraemia and the association between community-onset infection and outcome. From August 2007 to July 2011, demographic, clinical and microbiological data were prospectively collected on patients with MSSA bacteraemia. Patients were followed until death, hospital discharge or recovery from infection. Multivariate logistic regression was used to determine the association between community-onset infection and 30-day mortality. A total of 403 bacteraemic episodes occurred in 392 patients. Overall, there were 44 deaths (11.2%; 95% confidence interval: 7.9-14.0%) at 7 days and 101 deaths (25.8%; 21.5-30.4%) at 30 days. The difference in 30-day mortality between patients with community-onset and hospital-acquired infection was 71/256 (27.7%) versus 31/147 21.1%). Community-onset infection more frequently caused infective endocarditis (13/14, 92.9%), vertebral osteomyelitis (12/13, 92.3%) and skin and soft tissue infection (61/71, 85.9%) whereas intravascular catheter-associated infections were predominantly hospital-acquired (60/82, 73.2%). Age, Pitt score, Charlson comorbidity index (CCI), specific sites of infection (skin and soft tissue, lower respiratory tract and peripheral joints) and delay in appropriate treatment were strongly associated with 30-day mortality. In multivariate analysis, after adjustment for age, CCI and delay in appropriate treatment, community-onset infection was strongly associated with 30-day mortality (odds ratio: 1.59; 95% confidence interval: 0.91-2.80). Compared with hospital-acquired MSSA bacteraemic infection, community-onset infection was associated with worse 30-day outcomes. Hospital-acquired MSSA bacteraemic infections were rarely metastatic, frequently associated with medical devices and patients had better outcomes.


A structured evaluation of cryopreservation in generating single-cell transcriptomes from cerebrospinal fluid.
Single-cell transcriptomics allows characterization of cerebrospinal fluid (CSF) cells at an unprecedented level. Here, we report a robust cryopreservation protocol adapted for the characterization of fragile CSF cells by single-cell RNA sequencing (RNA-seq) in moderate- to large-scale studies. Fresh CSF was collected from twenty-one participants at two independent sites. Each CSF sample was split into two fractions: one was processed fresh, while the second was cryopreserved for months and profiled after thawing. B and T cell receptor sequencing was also performed. Our comparison of fresh and cryopreserved data from the same individuals demonstrates highly efficient recovery of all known CSF cell types. We find no significant difference in cell type proportions and cellular transcriptomes between fresh and cryopreserved cells. Results were comparable at both sites and with different single-cell sequencing chemistries. Cryopreservation did not affect recovery of T and B cell clonotype diversity. Our CSF cell cryopreservation protocol provides an important alternative to fresh processing of fragile CSF cells.


Diurnal intraocular pressure reduction with latanoprost 0.005% compared to timolol maleate 0.5% as monotherapy in subjects with exfoliation glaucoma.
To compare the diurnal intraocular pressure (IOP) efficacy and safety of timolol vs latanoprost in subjects with exfoliation glaucoma (XFG). A 3-month prospective, single-masked, active-controlled, parallel comparison performed in six centres in Greece that randomized subjects in a 1 : 1 ratio to either latanoprost in the evening (2000 hours) and placebo in the morning (0800 hours), or timolol twice daily (0800 and 2000 hours). In all, 103 subjects completed the study. After 3 months of chronic dosing, the latanoprost group exhibited a trend to a greater diurnal IOP reduction from an untreated baseline (24.9+/-3.2-17.4+/-2.9) compared with timolol (24.7+/-2.8-18.3+/-1.9 mmHg) (P=0.07). Latanoprost showed a significantly greater IOP reduction at 0800 hours (-8.5 vs -6.0 mm Hg for timolol, P<0.0001) whereas no difference was observed between the two medications at 1000, 1400, and 2000 hours after a Bonferroni Correction. In addition, latanoprost demonstrated a narrower range of diurnal IOP (2.4) than timolol (3.2 mmHg)(P=0.0017). Safety was similar between groups, except there was more conjunctival hyperaemia with latanoprost (n=8) than timolol (n=1)(P=0.01). This study suggests that latanoprost provides a statistically lower 08:00-hour IOP and better range of IOP than timolol in the treatment of XFG glaucoma.


Risk factors for Fasciola hepatica infection in children: a case-control study.
We conducted a case-control study to clarify the risk factors for human fascioliasis in the Northern Peruvian Altiplano. Cases (n=61) were individuals who were diagnosed as having chronic fascioliasis by faecal and/or serologic (Fas2-ELISA) studies. Controls (n=61) had negative serologic and coprological results for Fasciola hepatica. We identified an association between fascioliasis and four variables (40 analysed): the habit of drinking alfalfa juice (OR=4.5; 95% CI 1.8-11.1; P<0.001); familiarity with aquatic plants (OR=4.3; 95% CI 1.8-10.6; P<0.001); dog ownership (OR=5; 95% CI 1.7-15.1; P=0.002); and raising more than five sheep (OR=0.3; 95% CI 0.1-0.8; P=0.01). According to clinical presentation and laboratory studies, dizzy spells (P=0.01), history of jaundice (P=0.01), peripheral eosinophilia (P=0.005) and Ascaris lumbricoides in stools (P=0.001) were associated with fascioliasis. The principal exposure factor for F. hepatica infection was drinking alfalfa juice. In conclusion, we suggest that human fascioliasis in Peru should be suspected in patients from livestock-rearing areas, who present with recurrent episodes of jaundice and who have a history of consumption of alfalfa juice or aquatic plants, or who have eosinophilia.


Effect and Mechanism of LRP6 on Cardiac Myocyte Ferroptosis in Myocardial Infarction.
This study was aimed at exploring the biological function and molecular mechanism of ferroptosis of LRP6 modulation in cardiomyocytes of myocardial infarction (MI). We established the ferroptosis model of MI in vivo and in vitro and constructed the modulation network of circRNA-miRNA-LRP6 by bioinformatics analysis; then, we focused on exploring the regulatory relationship of LRP6 and its upstream genes circRNA1615 and miR-152-3p in the RIP experiments and the double luciferase reporter gene assay. Also, we tested the LRP6-mediated autophagy-related ferroptosis in MI. Ferroptosis was found in cardiomyocytes of MI, and ferroptosis inhibitor Ferrostatin-1 (Fer-1) could improve the pathological process of MI. LRP6 was involved in the process of ferroptosis in cardiomyocytes, and LRP6 deletion regulated ferroptosis in cardiomyocytes through autophagy. Screening and identification of the upstream gene circRNA1615 would target LRP6. circRNA1615 inhibited ferroptosis in cardiomyocytes, and circRNA1615 could regulate the expression of LRP6 through sponge adsorption of miR-152-3p, prevent LRP6-mediated autophagy-related ferroptosis in cardiomyocytes, and finally control the pathological process of MI. circRNA1615 inhibits ferroptosis via modulation of autophagy by the miRNA152-3p/LRP6 molecular axis in cardiomyocytes of myocardial infarction.


Elicitation of Th1/Th2 related responses in mice by chitosan nanoparticles loaded with Brucella abortus malate dehydrogenase, outer membrane proteins 10 and 19.
Brucella spp. is the causative agent of brucellosis, one of the worldwide diseases. The pathogen infects humans and animals mainly through the digestive or respiratory tract. Therefore, induction of mucosal immunity is required as the first line of defense. In this study, three Brucella abortus recombinant proteins, malate dehydrogenase (rMdh), outer membrane proteins (rOmp) 10 and 19 were loaded in mucoadhesive chitosan nanoparticles (CNs) and induction of mucosal and systemic immunity were investigated after intranasal immunization of BALB/c mice. These antigens were also coimmunized as cocktail (rCocktail) to evaluate multiple antigen specific vaccine candidates. At 6-weeks post-immunization (wpi), antigen specific total IgG was increased in all of the immunized groups, predominantly IgG1. In addition, spleenocyte from rMdh-, rOmp19-, and rCocktail-immunized groups significantly produced IFN-γ and IL-4 suggesting the induction of a mixed Th1-Th2 response. For mucosal immunity, anti-Mdh IgA from nasal washes and fecal excretions, and anti-Omps IgA from sera, nasal washes, genital secretions and fecal excretions were significantly increased in single antigen immunized groups. In the rCocktail-immunized group, anti-Mdh IgA were significantly increased while anti-Omps IgA was not. Collectively, this study indicates that comprise of B. abortus antigen-loaded CNs elicited the antigen-specific IgA with a Th2-polarized immune responses and combination of the highly immunogenic antigens elicited IgG specific to each type of antigen.


Activity of immobilized papain dehydrated by n-propanol in low-water media.
A propanol-rinsed enzyme preparations (PREP) of papain showed an activity of 59 nmol min(-1) (mg powder)(-1) in tert-butanol at the optimal water activity of 0.2. The immobilized papain was stable in aqueous media for 3 d at 4 degrees C. Solid-state buffers (bases and their HCl salts) suspended in the organic medium decreased the initial rate in all cases tested. The operational stability during Z-Gly-Phe-NH2 synthesis was improved when solid cysteine was added, doubling the yield after 24 h.


Differential protein expression of mitogen-activated protein kinases in erythrocytes and liver of lamprey Lampetra fluviatilis on the course of prespawning starvation.
The study was designed to identify the types of mitogen-activated protein kinases (MAPKs) in erythrocytes and liver tissues of river lamprey Lampetra fluviatilis and monitor the changes in protein expression levels of found enzymes on the course of prespawning starvation (from November to the end of May). Immunoreactivity of the native and phosphorylated forms of ERK1/2, JNK and p38 was examined in the cytosolic and membrane cell fractions. Both lamprey erythrocytes and liver were found to highly express ERK1/2 and JNK, whereas only trace amounts of p38 were revealed in hepatic tissues. ERK1/2 was identified in cytosolic and membrane fractions, whereas JNK and p38 were predominantly cytosolic enzymes. Total cellular amounts of ERK1/2 and phospho-ERK1/2 in both erythrocytes and liver tissues appeared to be relatively stable on the course of prespawning starvation. However, before spawning ERK1/2 translocated from cytosol to membranes, with partial decline of its cytoplasmic expression being compensated by increases in membrane-bound pool. Immunoreactivity of cytoplasmic JNK, phospho-JNK and p38 were stable from November to March, but sharply decreased before spawning exhibiting almost negligible levels in May, which suggests the depletion of their cellular fractions. Most probably, ERK1/2 plays more important role in mediating adaptive responses of erythrocytes and liver tissues to conditions of natural starvation and maintenance of cell viability before spawning and death of animals in May.


The action of neurotensin on single myenteric neurones.
The action of neurotensin was studied on single myenteric neurones within ganglia of the myenteric plexus isolated from the guinea-pig ileum. Drugs were applied by adding them to the perfusing Krebs solution. Extracellular recording with glass suction electrodes indicated that neurotensin (100 pM-300 nM) caused a dose-dependent excitation of about 50% of myenteric neurones; the remaining neurones were unaffected. This effect persisted in calcium-free solutions. Intracellular recording showed that a similar proportion of Type 1 myenteric neurones were depolarized by neurotensin: this was associated with an increase in membrane resistance. Type 2 cells were either depolarized or hyperpolarized by neurotensin. The depolarization persisted in calcium-free solutions. The hyperpolarization disappeared in calcium-free solutions, suggesting either that the potential change itself is calcium-dependent or that it was due to release by neurotensin of a hyperpolarizing substance.


Periodic fouling control strategies in gravity-driven membrane bioreactors (GD-MBRs): Impact on treatment performance and membrane fouling properties.
This study aims to assess the effects of periodic membrane fouling control strategies in Gravity-Driven Membrane Bioreactor (GD-MBR) treating primary wastewater. The impact of each control strategy on the reactor performance (permeate flux and water quality), biomass morphology, and fouling composition were evaluated. The application of air scouring coupled with intermittent filtration resulted in the highest permeate flux (4 LMH) compared to only intermittent filtration (i.e., relaxation) (1 LMH) and air scouring under continuous filtration (2.5 LMH). Air scouring coupled with relaxation led to a thin (~50 μm) but with more porous fouling layer and low hydraulic resistance, presenting the lowest concentration of extracellular polymeric substance (EPS) in the biomass. Air scouring under continuous filtration led to a thin (~50 μm), dense, compact, and less porous fouling layer with the highest specific hydraulic resistance. The employment of only relaxation led to the highest fouling formation (~280 μm) on the membrane surface. The highest TN removal (~62%) was achieved in the reactor with only relaxation (no aeration) due to the anoxic condition in the filtration tank, while the highest COD removal (~ 60%) was achieved with air scouring under continuous filtration due to the longer aeration time and the denser fouling layer. The results highlighted the importance of performing in-depth fouling characterization to link the membrane fouling properties to the hydraulic resistance and membrane bioreactor performances (i.e., water quality and water production). Moreover, this work proven the versatility of the GD-MBR, where the choice of the appropriate operation and fouling control strategy relies on the eventual discharge or reuse of the treated effluent.


Marginal association of fasting blood glucose with the risk of cystic fibrosis-related diabetes.
Cystic fibrosis-related diabetes (CFRD) may be diagnosed by fasting blood glucose ≥ 7.0 mmol/L and/or glucose ≥ 11.1 mmol/L following oral glucose tolerance test (OGTT). We compared the role of fasting and stimulated glucose for diagnosis of CFRD. We performed a cross-sectional review of the prevalence of fasting glycemic abnormalities and Kaplan-Meier survival analysis of risk of progression to CFRD according to baseline fasting glucose in the prospective Montreal Cystic Fibrosis Cohort. Isolated fasting hyperglycemia was detected in only 8% of participants at study onset. Eighty percent of subjects had isolated post-challenge hyperglycemia on their first OGTT meeting criteria for CFRD. Kaplan Meier survival analysis demonstrated that impaired fasting glucose (IFG) alone is not a risk factor for CFRD. Subjects with combined IFG and impaired glucose tolerance at baseline (IGT) had the highest risk of progression to CFRD. Post-prandial elevations in blood glucose are more common at diagnosis of CFRD. While IGT is a significant risk factor for CFRD, IFG alone is uncommon and does not increase the risk of CFRD. Patients with both IGT and IFG have the highest risk of CFRD.


Associations between adverse childhood experiences and obstetrical outcomes in a predominantly Black-identifying and low-income pregnant population.
Recent literature indicates that adverse childhood experiences have been associated with poor obstetrical outcomes, including pregnancy loss, preterm birth, and low birthweight. Several studies have been conducted in primarily self-identified White individuals who report middle to high income levels. Less is known about the impact of adverse childhood experiences on obstetrical outcomes in minority-identifying and low-income populations, who are known to experience a greater number of adverse childhood experiences and are at higher risk of maternal morbidity. This study aimed to examine associations between adverse childhood experiences and a broad range of obstetrical outcomes among predominantly Black-identifying pregnant persons who have low income and live in an urban area. This is a single-center retrospective cohort study of pregnant persons referred to a mental healthcare manager because of elevated psychosocial risks identified by screening tools or provider concerns during the study period from April 2018 to May 2021. Pregnant persons aged <18 years and those who did not speak English were excluded. Patients completed validated mental and behavioral health screening tools including the Adverse Childhood Experiences Questionnaire. Medical charts were reviewed for obstetrical outcomes, including preterm birth, low birthweight, hypertensive disorders of pregnancy, gestational diabetes mellitus, chorioamnionitis, sexually transmitted infection, maternal group B streptococcus carrier status, type of delivery, and attendance of a postpartum visit. Associations between high (≥4) and very high (≥6) of 10 adverse childhood experience score and obstetrical outcomes were analyzed using bivariate analysis and multivariate logistic regression, adjusting for confounding factors (significant at P<.05 in bivariate analysis). Our cohort included 192 pregnant persons, of whom 176 (91.7%) self-identified as Black or African American and 181 (94.8%) had public insurance (used as a proxy for low income). Adverse childhood experience score ≥4 was reported by 91 (47.4%) individuals and score ≥6 by 50 (26%). On univariate analysis, adverse childhood experience score ≥4 was associated with preterm birth (odds ratio, 2.17; 95% confidence interval, 1.02-4.61). Adverse childhood experience score ≥6 was associated with hypertensive disorders of pregnancy (odds ratio, 2.09; 95% confidence interval, 1.05-4.15) and preterm birth (odds ratio, 2.29; 95% confidence interval, 1.05-4.96). After accounting for chronic hypertension, associations between adverse childhood experience score and obstetrical outcomes were no longer significant. Approximately half of the pregnant persons referred to a mental healthcare manager had a high adverse childhood experience score, underscoring the high burden of childhood trauma on populations facing long-standing systemic racism and barriers to healthcare access. High and very high adverse childhood experience score may be associated with chronic health conditions that predate pregnancy and can alter obstetrical outcomes. Obstetrical care providers have a unique opportunity to mitigate risk of associated poor health outcomes during preconception and prenatal care by screening for adverse childhood experiences.


Patterns of Coping With Cyberbullying: Emotional, Behavioral, and Strategic Coping Reactions Among Middle School Students.
The aim of the present study was to examine coping patterns among victims of cyberbullying in middle school. The study included 232 adolescents, of whom 20.7% reported having been the victim of cyberbullying. Findings show that the most common emotional reactions to cyberbullying among the cyber victims were anger, rage, and frustration. The most commonly found behavioral reactions to cyberbullying were informing a friend, counterattacking, and ignoring the cyber incident. Examining the types of coping strategies that were used, we found that the victims of cyberbullying reported a lower use of problem-focused coping strategies for stressful situations, compared to adolescents who were not cyber victims; in addition, cyber victims also reported a much greater use of emotionally focused coping strategies and avoidance-focused strategies, compared to adolescents who were not cyber victims.


Tumor necrosis factor alpha activates transcription of the NADPH oxidase organizer 1 (NOXO1) gene and upregulates superoxide production in colon epithelial cells.
NADPH oxidase 1 (Nox1) is a multicomponent enzyme consisting of p22(phox), Nox organizer 1 (NOXO1), Nox1 activator 1, and Rac1. Interleukin-1beta, flagellin, interferon-gamma, and tumor necrosis factor alpha (TNF-alpha) similarly induced Nox1 in a colon cancer cell line (T84), whereas only TNF-alpha fully induced NOXO1 and upregulated superoxide-producing activity by ninefold. This upregulation was canceled by knockdown of NOXO1 with small interfering RNAs. TNF-alpha rapidly phosphorylated p38 mitogen-activated protein kinase and c-Jun N-terminal kinase 1/2, followed by phosphorylation of c-Jun and c-Fos and appearance of an AP-1 binding activity within 30 min. We cloned the 5' flank of the human NOXO1 gene (-3888 to +263 bp), and found that the region between -585 and -452 bp, which contains consensus elements of YY-1, AP-1, and Ets, and the GC-rich region encoding three putative binding sites for SP-1, was crucial for TNF-alpha-dependent promoter activity. Serial mutation analysis of the elements identified an AP-1 binding site (from -561 to -551 bp, agtAAGtcatg) as a crucial element for TNF-alpha-stimulated transcription of the human NOXO1 gene, which was also confirmed by the AP-1 decoy experiments. Thus, TNF-alpha acts as a potent activator of Nox1-based oxidase in colon epithelial cells, suggesting a potential role of this oxidase in inflammation of the colon.


Circulating aldosterone and mortality in female nursing home residents.
To date studies evaluating the relation between circulating aldosterone levels and mortality in elderly female individuals are lacking. We therefore aimed to assess the relationship between circulating aldosterone levels and mortality in a population-based cohort study of female nursing home residents. Individuals aged 70years and older were recruited from 95 nursing homes in Austria. Participants were enrolled and followed up by mobile study teams. All participants underwent an extensive health examination and were followed until death or end of the study. Serum aldosterone concentration (SAC) was measured at baseline after exclusion of twenty seven patients taking mineralocorticoid-receptor (MR) blockers. Median SAC was 171.1 (IQR: 103.2-303.4) pg/mL (normal range: 30-400) in 471 female individuals (mean age: 83.7±6.2years). After a median follow-up of 27±8months, a total of 121 (25.7%) participants died. In multivariable Cox proportional hazard analysis, SAC levels stratified in quartiles were significantly associated with all-cause mortality. Compared with the reference (first) SAC quartile, the Cox proportional hazard ratio (confidence interval 95%) for the fourth SAC quartiles was 1.94, 95% CI=1.08-3.46, p=0.026. We found statistically significant interaction terms between SAC-related mortality and the presence of advanced heart failure (NYHA functional class III; p=0.038), HbA1c (p=0.043) and eGFR levels (p=0.030). Higher circulating aldosterone levels are related to an increased mortality risk in elderly female nursing home residents. Interventional studies are needed to assess the potential influence of MR blockade on "hard" clinical outcomes in individuals aged 70years and older.


Biomechanical insights into the aetiology of infraspinatus syndrome.
Infraspinatus syndrome (IS) results from injury to the suprascapular nerve. For reasons that are poorly understood, volleyball players are at greater risk of developing IS than are athletes who compete in other overhead sports. Differences between the shoulder kinematics of volleyball-related overhead skills and those skills demanded by other overhead sports might explain the pronounced prevalence of IS among volleyball athletes. Observational, laboratory-based, cross-sectional study. The American Sports Medicine Institute. Fourteen healthy female Division 1 collegiate volleyball athletes. Upper limb biomechanics of 14 healthy female Division 1 collegiate volleyball athletes while spiking and serving were quantified, then compared to the results from data previously obtained from female baseball pitchers and tennis players. Although the general movement pattern at the shoulder girdle is qualitatively similar for the upper limb skills required by a variety of overhead sports, volleyball spiking and serving result in greater shoulder abduction and horizontal adduction at the moment of ball contact/release than do baseball pitching or tennis serving. The authors suggest that the unique scapular mechanics which permit the extreme shoulder abduction and horizontal adduction that characterise volleyball spiking and serving place anatomically predisposed volleyball athletes at increased risk for developing cumulative traction-related injury to the suprascapular nerve at the level of the spinoglenoid notch.


Ecotoxicological assessment of guanitoxin-producing cyanobacteria in Danio rerio and Daphnia similis.
Anthropogenic activity has dramatically deteriorated aquatic ecosystems in recent years. Such environmental alterations could change the primary producers' composition, exacerbating the proliferation of harmful microorganisms such as cyanobacteria. Cyanobacteria can produce several secondary metabolites, including guanitoxin, a potent neurotoxin and the only naturally occurring anticholinesterase organophosphate ever reported in the literature. Therefore, this study investigated the acute toxicity of guanitoxin-producing cyanobacteria Sphaerospermopsis torques-reginae (ITEP-024 strain) aqueous and 50% methanolic extracts in zebrafish (Danio rerio) hepatocytes (ZF-L cell line), zebrafish embryos (fish embryo toxicity - FET) and specimens of the microcrustacean Daphnia similis. For this, hepatocytes were exposed to 1-500 mg/L of the ITEP-024 extracts for 24 h, the embryos to 31.25-500 mg/L for 96 h, and D. similis to 10-3000 mg/L for 48 h. Non-target metabolomics was also performed to analyze secondary metabolites produced by the ITEP-024 using LC-MS/MS. Metabolomics indicated the guanitoxin presence just in the aqueous extract of the ITEP-024 and the presence of the cyanopeptides namalides, spumigins, and anabaenopeptins in the methanolic extract. The aqueous extract decreased the viability of zebrafish hepatocytes (EC(I)50(24h) = 366.46 mg/L), and the methanolic extract was not toxic. FET showed that the aqueous extract (LC50(96) = 353.55 mg/L) was more toxic than the methanolic extract (LC50(96) = 617.91 mg/L). However, the methanolic extract had more sublethal effects, such as abdominal and cardiac (cardiotoxicity) edema and deformation (spinal curvature of the larvae). Both extracts immobilized daphnids at the highest concentration analyzed. However, the aqueous extract was nine times more lethal (EC(I)50(48h) = 108.2 mg/L) than the methanolic extract (EC(I)50(48h) = 980.65 mg/L). Our results showed an imminent biological risk for aquatic fauna living in an ecosystem surrounded by ITEP-024 metabolites. Our findings thus highlight the urgency of understanding the effects of guanitoxin and cyanopeptides in aquatic animals.


Child-Sum EATree-LSTMs: enhanced attentive Child-Sum Tree-LSTMs for biomedical event extraction.
Tree-structured neural networks have shown promise in extracting lexical representations of sentence syntactic structures, particularly in the detection of event triggers using recursive neural networks. In this study, we introduce an attention mechanism into Child-Sum Tree-LSTMs for the detection of biomedical event triggers. We incorporate previous researches on assigning attention weights to adjacent nodes and integrate this mechanism into Child-Sum Tree-LSTMs to improve the detection of event trigger words. We also address a limitation of shallow syntactic dependencies in Child-Sum Tree-LSTMs by integrating deep syntactic dependencies to enhance the effect of the attention mechanism. Our proposed model, which integrates an enhanced attention mechanism into Tree-LSTM, shows the best performance for the MLEE and BioNLP'09 datasets. Moreover, our model outperforms almost all complex event categories for the BioNLP'09/11/13 test set. We evaluate the performance of our proposed model with the MLEE and BioNLP datasets and demonstrate the advantage of an enhanced attention mechanism in detecting biomedical event trigger words.


Metabolism of 2-hydroxy-4-methoxybenzophenone in isolated rat hepatocytes and xenoestrogenic effects of its metabolites on MCF-7 human breast cancer cells.
The metabolism and cytotoxicity of 2-hydroxy-4-methoxybenzophenone (HMB) in isolated rat hepatocytes and the xenoestrogenic activity of HMB and its metabolites in MCF-7 human breast cancer cells and an estrogen receptor competitive binding assay have been studied, respectively. The incubation of hepatocytes with HMB caused a concentration- and time-dependent decrease in cell viability, accompanied by loss of intracellular ATP and adenine nucleotide pools. HMB at a low-toxic level (0.25 mM) in the hepatocyte suspensions was converted enzymatically to 2,4-dihydroxybenzophenone (DHB) and a hydroxylated intermediate, which was tentatively identified as an isomer of 2,2prime prime or minute-dihydroxy-4-methoxybenzophenone (DHMB) as determined by mass spectroscopy coupled with HPLC. Furthermore, the parent compound and both intermediates were rapidly conjugated to glucuronides, whereas free unconjugated DHMB and 2,3,4-trihydroxybenzophenone (THB) were identified as trace intermediates. In another experiment, DHB and THB displaced competitively 17beta-estradiol bound to the recombinant human estrogen receptor alpha in a concentration-dependent manner: IC(50) of diethylstilbestrol and bisphenol A, which are known xenoestorogenic compounds, and DHB and THB was approximately 1 x 10(-8), 1 x 10(-5), 5 x 10(-5) and 5 x 10(-4) M, respectively. Further, DHB at concentrations from 10(-8) to 10(-6) M caused a concentration-dependent proliferation of MCF-7 cells. DHMB and THB at 10(-7) and 10(-6) M also elicited a slight increase in cell numbers, whereas HMB at concentrations from 10(-9) to 10(-4) M did not affect the cell proliferation. Based on the relative IC50 for the competitive binding and the proliferative effect on MCF-7 cells, it follows that in estrogenic potency, DHB>THB>DHMB. These results indicate that some hydroxylated intermediates such as DHB rather than the parent compound act as a xenoestrogen via biotransformation.


Aquaporins and cell migration.
Aquaporin (AQP) water channels are expressed primarily in cell plasma membranes. In this paper, we review recent evidence that AQPs facilitate cell migration. AQP-dependent cell migration has been found in a variety of cell types in vitro and in mice in vivo. AQP1 deletion reduces endothelial cell migration, limiting tumor angiogenesis and growth. AQP4 deletion slows the migration of reactive astrocytes, impairing glial scarring after brain stab injury. AQP1-expressing tumor cells have enhanced metastatic potential and local infiltration. Impaired cell migration has also been seen in AQP1-deficient proximal tubule epithelial cells, and AQP3-deficient corneal epithelial cells, enterocytes, and skin keratinocytes. The mechanisms by which AQPs enhance cell migration are under investigation. We propose that, as a consequence of actin polymerization/depolymerization and transmembrane ionic fluxes, the cytoplasm adjacent to the leading edge of migrating cells undergoes rapid changes in osmolality. AQPs could thus facilitate osmotic water flow across the plasma membrane in cell protrusions that form during migration. AQP-dependent cell migration has potentially broad implications in angiogenesis, tumor metastasis, wound healing, glial scarring, and other events requiring rapid, directed cell movement. AQP inhibitors may thus have therapeutic potential in modulating these events, such as slowing tumor growth and spread, and reducing glial scarring after injury to allow neuronal regeneration.


Enantiospecific Alkynylation of Alkylboronic Esters.
Enantioenriched secondary and tertiary alkyl pinacolboronic esters undergo enantiospecific deborylative alkynylation through a Zweifel-type alkenylation followed by a 1,2-elimination reaction. The process involves use of α-lithio vinyl bromide or vinyl carbamate species, for which application to Zweifel-type reactions has not previously been explored. The resulting functionalized 1,1-disubstituted alkenes undergo facile base-mediated elimination to generate terminal alkyne products in high yield and excellent levels of enantiospecificity over a wide range of pinacolboronic ester substrates. Furthermore, along with terminal alkynes, internal and silyl-protected alkynes can be formed by simply introducing a suitable carbon- or silicon-based electrophile after the base-mediated 1,2-elimination reaction.


Magnetic nanoparticles sensitize MCF-7 breast cancer cells to doxorubicin-induced apoptosis.
Resistance of breast cancer cells to the available chemotherapeutics is a major obstacle to successful treatment. Recent studies have shown that magnetic nanoparticles might have significant application in different medical fields including cancer treatment. The goal of this study is to verify the ability of magnetic nanoparticles to sensitize cancer cells to the clinically available chemotherapy. The role of iron oxide nanoparticles, static magnetic field, or a combination in the enhancement of the apoptotic potential of doxorubicin against the resistant breast cancer cells, MCF-7 was evaluated using the MTT assay and the propidium iodide method. In the present study, results revealed that pre-incubation of MCF-7 cells with iron oxide nanoparticles before the addition of doxorubicin did not enhance doxorubicin-induced growth inhibition. Pre-incubation of MCF-7 cells with iron oxide nanoparticles followed by a static magnetic field exposure significantly (P < 0.05) increased doxorubicin-induced cytotoxicity. Sensitization with pre-exposure to the magnetic field was dose-dependent where the highest cytotoxicity was seen at 1 tesla. Further experiments revealed that the anti-proliferative effect of this treatment procedure is due to induction of apoptotic cell death. These results might point to the importance of combining magnetic nanoparticles with a static magnetic field in treatment of doxorubicin-refractory breast cancer cells.


Absolute measurement of cellular activities using photochromic single-fluorophore biosensors and intermittent quantification.
Genetically-encoded biosensors based on a single fluorescent protein are widely used to visualize analyte levels or enzymatic activities in cells, though usually to monitor relative changes rather than absolute values. We report photochromism-enabled absolute quantification (PEAQ) biosensing, a method that leverages the photochromic properties of biosensors to provide an absolute measure of the analyte concentration or activity. We develop proof-of-concept photochromic variants of the popular GCaMP family of Ca2+ biosensors, and show that these can be used to resolve dynamic changes in the absolute Ca2+ concentration in live cells. We also develop intermittent quantification, a technique that combines absolute aquisitions with fast fluorescence acquisitions to deliver fast but fully quantitative measurements. We also show how the photochromism-based measurements can be expanded to situations where the absolute illumination intensities are unknown. In principle, PEAQ biosensing can be applied to other biosensors with photochromic properties, thereby expanding the possibilities for fully quantitative measurements in complex and dynamic systems.


Effect of different C3-aryl substituents on the antioxidant activity of 4-hydroxycoumarin derivatives.
The antioxidant activity of 4-hydroxycoumarin synthetic derivatives and 4-methylumbelliferone were determined taking 4-hydroxycoumarin as the reference compound. Six 3-aryl-4-hydroxycoumarin derivatives were synthesized from 4-hydroxycoumarin as precursor in order to evaluate changes in their antioxidant properties due to C3-aryl substituent nature. Free radical scavenging capacities of these compounds against two different species DPPH(·) and ABTS(·+) and the protecting ability towards the β-carotene-linoleic acid co-oxidation enzymatically induced by lipoxygenase were measured. In addition, the relationship between the activities of these molecules against DPPH radical and the bond dissociation energy of O-H (BDE) calculated using methods of computational chemistry was evaluated.


The heat shock response in congeneric land snails (Sphincterochila) from different habitats.
Land snails are subject to daily and seasonal variations in temperature and in water availability, and use heat shock proteins (HSPs) as part of their survival strategy. We used experimental heat stress to test whether adaptation to different habitats affects HSP expression in two closely related Sphincterochila snail species, a desert species, Sphincterochila zonata, and a Mediterranean-type species, Sphincterochila cariosa. Our findings show that in S. cariosa, heat stress caused rapid induction of Hsp70 proteins and Hsp90 in the foot and kidney tissues, whereas the desert-inhabiting species S. zonata displayed delayed induction of Hsp70 proteins in the foot and upregulation of Hsp90 alone in the kidney. Our study suggests that Sphincterochila species use HSPs as part of their survival strategy following heat stress and that adaptation to different habitats results in the development of distinct strategies of HSP expression in response to heat, namely the reduced induction of HSPs in the desert-dwelling species. We suggest that the desert species S. zonata relies on mechanisms and adaptations other than HSP induction, thus avoiding the fitness consequences of continuous HSP upregulation.


Quality Of Life And Relationship Between Functioning And Symptoms Of Female Patients With Breast Cancer Before Chemotherapy In A Cancer Clinic At Yangon,Myanmar.
Better quality of life (QOL) is associated with longer survival in cancer patients. This study evaluated the QOL and relationship between functioning and symptoms among female breast cancer patients before chemotherapy. Cross-sectional study was conducted by including 74 participants attending a cancer clinic. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire(s)-Core30 was applied for assessing QOL. It was composed of three domains namely global health status/QOL, functioning (includes five categories) and symptoms (includes nine categories). Pearson correlation and multiple linear regression were performed to find the relationship between functioning and symptoms in participants. The study was approved by Institutional Review Board of Defence Services Medical Research Centre, Myanmar with approval number IRB/2018/34. Global health status/QOL score was fair (61.8±20.1). Among the five categories of functioning, cognitive functioning score (83.6±19.8) was the highest and role functioning score (66.4±29.3) was the lowest. Among symptoms, insomnia score (29.3±30.7) was the highest and diarrhoea score (0.9±5.4) was the lowest. When Pearson correlation was performed, functioning and symptoms were negatively correlated. Fatigue had significant (p<0.001) moderate negative correlation with physical functioning, role functioning and emotional functioning, whereas pain with role functioning (p<0.001). When linear regression was performed, nausea & vomiting was the strongest predictor for impaired global health status/QOL (p<0.05), while fatigue was the strongest predictor for impairment in all five categories of functioning (p<0.05). Functioning and symptoms were negatively correlated in breast cancer patients. Nausea & vomiting and fatigue were the strongest predictors for impaired QOL.