Digestive hemorrhages of obscure origin.
The diagnosis of digestive bleeding in some cases can require a diagnostic laparotomy when other methods have been ineffective. Video-laparoscopy can provide such cases with a certain diagnosis and the possibility of performing a simultaneous surgical treatment. Our experience using video-laparoscopic to treat digestive hemorrhages of obscure origin involved 16 patients. The examined patients presented with the following diseases: Meckel's diverticulum (8 cases), gastric leiomyoma (1 case), small bowel leiomyoma (4 cases), jejunum leiomyosarcoma (1 case), small bowel melanoma (1 case), and Peutz-Jeghers syndrome (1 case). In all these patients the laparoscopic approach allowed us to identify the origin and site of the hemorrhages, and subsequently to treat the identified lesions. In one patient, an intraperitoneal resection of the diverticulum was performed using Endo-Gia (TM30NIF; Tyco Auto-Suture). In the remaining cases, a minilaparatomy was performed for resection of the disordered loop. Video-laparoscopy is very useful for avoiding explorative laparatomies on patients affected by digestive hemorrhages of obscure origin. In these cases, the video-laparoscopic approach allows full and meticulous explorations of the small bowel to be performed, and seems to be useful for diagnosis through direct observation of the lesions. Moreover, if necessary, video-laparoscopy can be used for the effective treatment of the diseases.


Keratitis in children as seen in a tertiary hospital in Africa.
Blindness studies have shown that keratitis complicated by the use of traditional eye medications is a major factor of childhood blindness in developing countries. Most cases of such keratitis were presumably due to nutritional causes or bacterial infection. The patterns of outcome that are seen in hospitals may be different. To determine the clinical types of keratitis seen in children at a tertiary hospital and compare with other reports. A retrospective analysis was conducted using the records of children who presented with keratitis to the eye unit of the University College Hospital, Ibadan, Nigeria, over a three-year period from January 2003 to December 2005. Information obtained were the demographic data, the etiological type of keratitis and visual outcome of management. Ninety-five patients with keratitis seen during this three-year period were children. Of these, 47 (49.5%) patients had presumed herpes simplex keratitis; 78.9% of children with herpes simplex keratitis presented with combined epithelial and stromal disease; 21 (22.1%) had keratitis that was associated with a recent measles infection and protein calorie malnutrition. Fifteen (15.8%) had keratitis associated with phlyctenular keratoconjunctivitis, eight (8.4%) patients had bacterial/fungal keratitis, while four (4.2%) had vernal ulcers. Both the right and left eyes were affected in 47.6% and 52.4% of cases, respectively. Bilateral keratitis occurred in eight of the children with measles, and six patients with herpes simplex keratitis. Fifty-nine eyes had visual acuity recorded after the keratitis healed. Of these, the visual outcome was very poor in six (20.0%) eyes with herpes simplex keratitis and eight (100%) eyes with bacterial/fungal keratitis. All eyes with suppurative keratitis associated with measles developed dense corneal scars or were perforated. Herpes simplex keratitis was the leading cause of keratitis in children seen at this tertiary hospital, and clinical presentations do not differ from those reported in other populations. Very poor visual outcome was associated with all types of keratitis except those with herpes keratitis. Blindness studies may underrepresent the burden of herpes simplex keratitis in the location of this study.


A six-point scoring system for antenatal cardiotocographs.
A six-point scoring system for antenatal cardiotocography based upon baseline fetal heart rate (FHR) ad FHR response to fetal movements and Braxton-Hicks contractions has been described and tested in 89 patients. The 'six-point score' obtained within 24 hours of delivery or death of the fetus (D--1) was shown to be strongly associated both with the one-minute Apgar score and the nutritional status of the infant as reflected by centile birth weight. In 21 patients whose D--1 'six-point score' was 4 or less, analysis ofthe cardiologicographs performed on the previous day (D--2) showed that 14 infants already showed evidence of hypoxia. In the remaining seven patients, however, the previous day's six-point score had been normal (5 or 6); in six of these patients a persistently low daily fetal movement count or placental abruption led to repeat cardiotocography. Hypoxia affected the three components of the score in a progressive manner. Firstly there were alterations in the response of the FHR to Braxton-Hicks contractions followed by changes in the FHR response to fetal movements. Finally, fetal movements ceased and baseline FHR changes occurred mainly in the form of a trachycardia. The method of scoring was simple to use and could standardize reporting.


The Doctor of Nursing Practice help desk: An innovative approach to developing evidence-based practice competency and providing DNP project support.
The 2021 American Association for Colleges of Nursing (AACN) Essentials for Professional Nursing Education identifies evidence-based practice (EBP) as a core concept meant to be integrated across curricula. Integrating EBP in Doctor of Nursing Practice (DNP) programs is challenging because of barriers including persistent confusion between research, EBP, and quality improvement; low faculty confidence and competence in their EBP skills and mentoring; increased faculty workload with growing program enrollments; and limited opportunities for students and faculty to practice EBP skills. The aim of this initiative was to implement and evaluate an innovative education strategy to build DNP students' and faculty's EBP competency and confidence while mitigating barriers faced by DNP programs. A DNP Help Desk was created and implemented at a large, Midwestern college of nursing with participation and support from EBP experts. Student and faculty participation were tracked, and perceptions of the help desk were evaluated. Opportunities to evolve the help desk were identified and implemented. Outcomes included a self-reported increase in student and faculty confidence and EBP competency, increased integration, and utilization of EBP in project work, elevated DNP project quality, and decreased demands on DNP project advisors. Engaging in innovative strategies aimed at increasing EBP competency and confidence may lead to increased EBP engagement and positive outcomes for students, faculty, and DNP programs.


Special issues related to breast cancer adjuvant therapy in older women.
Increasing age remains the major risk factor for breast cancer and more than half of all breast cancers in North America and the European Union occur in women 65 years and older. Anticipated life expectancy, co-morbidity, and functional status must all be considered when offering systemic adjuvant treatment to older women. Tamoxifen significantly decreases the risk of recurrence and improves survival in all women with hormone receptor-positive invasive breast cancer, including women 70 years and older. More recently, aromatase inhibitors have been shown to be even more effective than tamoxifen in reducing breast cancer recurrence in postmenopausal women, and are an appropriate choice for initial endocrine therapy in older women. Adjuvant chemotherapy improves survival in postmenopausal women, but adds little to endocrine therapy in the majority of women with node-negative, hormone receptor-positive tumors. Chemotherapy should be considered for patients with high-risk node-negative, hormone receptor-negative tumors and those with node-positive tumors. Co-morbidity and its effect on survival should be factored into all chemotherapy decisions. Older women are frequently under-treated and are still under-represented in clinical trials; sometimes this represents good clinical judgment, but age bias alone can result in under-treatment and higher breast cancer-related mortality or state-of-the-art trials not being offered to older, but otherwise eligible, patients. Physician education and more clinical trials designed for older women are needed.


Influence of state-2 transition on the proton motive force across the thylakoid membrane in spinach chloroplasts.
The proton motive force (pmf) across the thylakoid membrane is composed of the proton gradient and the membrane potential, which promotes millisecond-delayed light emission (ms-DLE). In this study, the time courses of LHC II phosphorylation and ms-DLE were investigated in spinach chloroplast during State-2 transition. Red light illumination resulted in an exponential rise in LHC II phosphorylation and a biphasic time course of ms-DLE. The phospho-LHC II appeared upon approximately 1 min illumination. The phosphorylation level increased exponentially when illumination was elongated to 20 min. The t((1/2) )of saturated LHC II phosphorylation was estimated 4-5 min under present illumination. During this process, the amplitudes of ms-DLE increased transiently to a maximal amplitude within 0.5 min illumination, and the reached maximum of the fast phase of ms-DLE was approximately 140% of the dark control. Then, ms-DLE decreased from the maximum. After > or =3 min illumination, ms-DLE decreased to a lower level than the dark control. In the presence of uncouplers and inhibitors, the transient increase in the biphasic time course of ms-DLE was removed by nigericin and DCMU, and the sequential decrease was delayed by DCCD. The time course was not affected significantly by valinomycin and DBMIB. Moreover, the level of LHC II phosphorylation was enhanced by nigericin, valinomycin and DCCD, and was inhibited completely by DCMU and partially by DBMIB. Taken together, we proposed that the PS II photochemical activity remained unaffected even with a higher level of LHC II phosphorylation, which was reflected by the effect of DCCD on the time course of ms-DLE. Probably, the evidence of LHC II phosphorylation is the rearrangement of LHC II-PS II complex and the thylakoid, a feedback to light-exposure, rather than the redistribution of excitation energy from PS II to PS I.


Isolation of clonal cultures of endosymbiotic green algae from their ciliate hosts.
Using Paramecium bursaria as a model organism improved protocols have been developed to isolate clonal endosymbiotic algae. This involved micromanipulation of individual protists, rupturing to release endosymbionts followed by enrichment on complex media and a series of plating steps, under low light (PAR ~10μmol photons m(-2)s(-1)).


Sub-chronic exposure to fipronil induced oxidative stress, biochemical and histopathological changes in the liver and kidney of male albino rats.
Fipronil (FPN) is a broad-spectrum N-phenylpyrazole insecticide and has been used in agriculture and public health since the mid-1990s. The present study was designed to investigate the adverse effects of sub-chronic exposure to the FPN on the liver and kidney of male rats at three concentrations 0.1, 1 and 10 mg/L in drinking water for 45 days. Serum aspartate aminotransferases (AST), alanine aminotransferases (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) activity and levels of uric acid, creatinine and total protein were significantly increased in FPN-treated rats. Oxidative stress biomarkers such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reduced (GSH) were significantly decreased, while lipid peroxidation (LPO) was significantly increased in treating rats in a concentration dependent manner. FPN caused histopathological alterations in liver and kidney of male rats. From our results, it can be concluded that FPN induced lipid peroxidation, oxidative stress, liver, and kidney injury in rats. These pathophysiological changes in liver and kidney tissues could be due to the toxic effect of FPN that associated with a generation of free radicals.


Degradation of vinyl ester resin and its composites via cleavage of ester bonds to recycle valuable chemicals and produce polyurethane.
Vinyl ester resins (VER) and its composites are widely used in chemical industry and municipal engineering. However, its dense three-dimensional network structure makes its degradation and recycling a great challenge. Herein, a novel, efficient and green degradation system gamma-valerolactone (GVL)-H2O/p-toluene sulfonic (PTSA) was developed to degrade VER and its composites. VER was completely degraded in the GVL-H2O/PTSA at 210 °C and 0.6 MPa. By combing SEM-EDS, IR, NMR, GPC and MALDI-TOF-MS analysis, it was clarified that VER swelled well in GVL, allowing the transfer of PTSA and H2O through the resin matrix. The ester bonds in VER were cleaved via hydrolysis with H2O catalyzed by the sulfonic acid of PTSA, and high value-added polymer products, i.e., copolymer of styrene and methacrylic acid (SMAA) and bisphenol-A diglycidyl ether (DGEBA), were recycled, which accounted for ca. 87.0 wt% of raw VER. DGEBA can be recycled to prepare a new PU material. The GVL-H2O/PTSA system was also effective for degrading UPR and VER-containing composites. This work provides a practical strategy for chemical degradation and recovery of thermoset VER resins.


Physiological endpoints in daphnid acute toxicity tests.
Daphnids are freshwater crustaceans used in toxicity tests. Although lethality and immobilisation are the most commonly used endpoints in those tests, more sensitive parameters are required for determination of sublethal acute effects of toxicants. The use of various physiological endpoints in daphnids is considered as a low-cost and simple alternative that meets the 3R's rule (Replacement, Reduction, Refinement) criteria. However, currently there is no review-based evaluation of their applicability in toxicity testing. This paper presents the results on the most commonly determined physiological parameters of Daphnia in ecotoxicological studies and human drug testing, such as feeding activity, thoracic limb movement, heart rate, cardiac area, respiratory activity, compound eye, mandible movements and post-abdominal claw contractions. Furthermore, their applicability as promising endpoints in the assessment of water quality or drug testing is discussed.


Childhood obesity and dental caries in homeless children.
Childhood obesity and dental caries are increasing epidemics, especially among children who are living below the poverty level. This study was conducted to determine the relationship between body mass index (BMI) and caries in homeless children. A secondary data analysis with a correlational design was used. A convenience sample of 157 children was recruited from a homeless shelter. Pearson's and partial correlations were used to explore the relationships among age, BMI, and caries. Most of the children were girls and were African American. Slightly more than half of the children were overweight (19.7%) or obese (30.6%) and had caries (50.3%). Significant positive correlations between age and BMI (p = .03) as well as between age and caries (p = .003) were found. As BMI increased, so did caries (p = .08). Consistent with reports from the Centers for Disease Control and Prevention, homeless children had higher BMI and caries rates than the national averages. Although a definitive conclusion between obesity and dental caries cannot be drawn, these two health issues are important areas for all pediatric health care providers to address at every visit.


Estimating the SARS-CoV2 infections detection rate and cumulative incidence in the World Health Organization African Region 10 months into the pandemic.
As of 03 January 2021, the WHO African region is the least affected by the coronavirus disease-2019 (COVID-19) pandemic, accounting for only 2.4% of cases and deaths reported globally. However, concerns abound about whether the number of cases and deaths reported from the region reflect the true burden of the disease and how the monitoring of the pandemic trajectory can inform response measures.We retrospectively estimated four key epidemiological parameters (the total number of cases, the number of missed cases, the detection rate and the cumulative incidence) using the COVID-19 prevalence calculator tool developed by Resolve to Save Lives. We used cumulative cases and deaths reported during the period 25 February to 31 December 2020 for each WHO Member State in the region as well as population data to estimate the four parameters of interest. The estimated number of confirmed cases in 42 countries out of 47 of the WHO African region included in this study was 13 947 631 [95% confidence interval (CI): 13 334 620-14 635 502] against 1 889 512 cases reported, representing 13.5% of overall detection rate (range: 4.2% in Chad, 43.9% in Guinea). The cumulative incidence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was estimated at 1.38% (95% CI: 1.31%-1.44%), with South Africa the highest [14.5% (95% CI: 13.9%-15.2%)] and Mauritius [0.1% (95% CI: 0.099%-0.11%)] the lowest. The low detection rate found in most countries of the WHO African region suggests the need to strengthen SARS-CoV-2 testing capacities and adjusting testing strategies.


A multiple sequence comparison method.
This article presents a new method for the comparison of multiple macromolecular sequences. It is based on a hierarchical sequence synthesis procedure that does not require any a priori knowledge of the molecular structure of the sequences or the phylogenetic relations among the sequences. It differs from the existing methods as it has the capability of: (i) generating a statistical-structural model of the sequences through a synthesis process that detects homologous groups of the sequences, and (ii) aligning the sequences while the taxonomic tree of the sequences is being constructed in one single phase. It produces superior results when compared with some existing methods.


Body composition in relation to postoperative anastomotic leakage and overall survival in patients with esophageal cancer.
Body composition was reported to be related to the prognosis of patients with cancer. This study aimed to investigate the influence of preoperative body composition on anastomotic leakage and overall survival in patients with esophageal cancer. In this retrospective study, 93 patients with esophageal cancers were evaluated. Skeletal muscle area, intermuscular adipose tissue, visceral adipose tissue (VAT), and subcutaneous adipose tissue were measured on computed tomography images at the level of the third lumbar vertebra. Subsequently, each body composition index was also calculated by dividing the body composition by the square of the height. The cut-off values of body compositions were defined using X-tile software (version 3.6.1; Yale University, New Haven, CTA). Univariate and multivariate analyses were performed to evaluate the risk factors of anastomotic leakage. Kaplan-Meier method and Cox regression analysis were used to evaluate the risk factors of overall survival. VAT and visceral fat index (VFI) were higher in patients with anastomotic fistula than in those without anastomotic fistula, but none of them were independent risk factors. Patients with higher body mass index (BMI), higher VFI, and higher subcutaneous fat index (SFI) had better overall survival. By multivariate analysis, SFI >27.6 cm2/m2 was still significantly associated with overall survival. Patients with higher VAT and VFI were prone to have an anastomotic leakage. Lower BMI, VFI, and SFI were associated with a reduction in overall survival.


Association of chronic kidney disease with abnormal cardiac mechanics and adverse outcomes in patients with heart failure and preserved ejection fraction.
Chronic kidney disease (CKD) is associated with worse outcomes in heart failure with preserved ejection fraction (HFpEF). Whether this association is due the effect of CKD on intrinsic abnormalities in cardiac function is unknown. We hypothesized that CKD is independently associated with worse cardiac mechanics in HFpEF. We prospectively studied 299 patients enrolled in the Northwestern University HFpEF Program. Using the creatinine-based CKD-Epi equation to calculate estimated glomerular filtration rate (eGFR), study participants were analysed by CKD status (using eGFR <60 mL/min/1.73 m(2) to denote CKD). Indices of cardiac mechanics (longitudinal strain parameters) were measured using speckle-tracking echocardiography. Using multivariable-adjusted linear and Cox regression analyses, we determined the association between CKD and echocardiographic parameters and clinical outcomes (cardiovascular hospitalization or death). Of 299 study participants, 48% had CKD. CKD (dichotomous variable) and reduced eGFR (continuous variable) were both associated with worse cardiac mechanics indices including left atrial (LA) reservoir strain, LV longitudinal strain, and right ventricular free wall strain even after adjusting for potential confounders, including co-morbidities, EF, and volume status. For example, for each 1-SD decrease in eGFR, LA reservoir strain was 3.52% units lower (P < 0.0001) after multivariable adjustment. Reduced eGFR was also associated with worse outcomes [adjusted hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.01-1.61 per 1-SD decrease in eGFR; P = 0.039]. The association was attenuated after adjustment for indices of cardiac mechanics (P = 0.064). In HFpEF, CKD is independently associated with worse cardiac mechanics, which may explain why HFpEF patients with CKD have worse outcomes. NCT01030991.


Automated chart filing on panoramic radiographs using deep learning.
The aim of this study is to automatically detect, segment and label teeth, crowns, fillings, root canal fillings, implants and root remnants on panoramic radiographs (PR(s)). As a reference, 2000 PR(s) were manually annotated and labeled. A deep-learning approach based on mask R-CNN with Resnet-50 in combination with a rule-based heuristic algorithm and a combinatorial search algorithm was trained and validated on 1800 PR(s). Subsquently, the trained algorithm was applied onto a test set consisting of 200 PR(s). F1 scores, as a measure of accuracy, were calculated to quantify the degree of similarity between the annotated ground-truth and the model predictions. The F1-score considers the harmonic mean of precison (positive predictive value) and recall (specificity). The proposes method achieved F1 scores up to 0.993, 0.952 and 0.97 for detection, segmentation and labeling, respectivley. The proposed method forms a promising foundation for the further development of automatic chart filing on PR(s). Deep learning may assist clinicians in summarizing the radiological findings on panoramic radiographs. The impact of using such models in clinical practice should be explored.


Aza-CGP37157-lipoic hybrids designed as novel Nrf2-inducers and antioxidants exert neuroprotection against oxidative stress and show neuroinflammation inhibitory properties.
Two multitarget hybrids, derived from an aza-analogue of CGP37157, a mitochondrial Na+ /Ca2+ exchanger antagonist, and lipoic acid were designed in order to combine in a single molecule the antioxidant and Nrf2 induction properties of lipoic acid and the neuroprotective activity of CGP37157. The hybrid derivatives showed Nrf2 induction and radical scavenging properties, leading to a good neuroprotective profile against oxidative stress, together with an interesting antineuroinflammatory activity. The results obtained show differences in activity depending on the configuration of the chiral center of LA.


The decreasing risk of reoperative aortic valve replacement: Implications for valve choice and transcatheter therapy.
Increasing use of bioprostheses for surgical aortic valve replacement (SAVR) in younger patients, together with wider use of transcatheter aortic valve replacement, necessitates understanding risks associated with surgical valve reintervention. Therefore, we sought to identify risks of reoperative SAVR compared with those of primary isolated SAVR. From January 1980 to July 2017, 7037 patients underwent nonemergency isolated SAVR, with 753 reoperations and 6284 primary isolated operations. These 2 groups were propensity score-matched on 46 preoperative variables, yielding 581 patient pairs for comparing outcomes. Among propensity score-matched patients, aortic clamp time (median 63 vs 52 minutes; P < .0001), cardiopulmonary bypass time (median 88 vs 67 minutes; P < .0001), and postoperative stay (median 7.1 vs 6.9 days; P = .003) were longer for reoperative SAVR than primary isolated SAVR. Hospital mortality after reoperative SAVR decreased from 3.4% in 1985 to 1.3% in 2011, similar to that of primary isolated SAVR. Occurrence of stroke, deep sternal wound infection, and new renal dialysis was similar. Blood transfusion (67% vs 36%; P < .0001) and reoperations for bleeding/tamponade (6.4% vs 3.1%; P = .009) were more common after reoperative SAVR. Survival at 1, 5, 10, and 20 years was 94%, 82%, 64%, and 33% after reoperative SAVR and 95%, 86%, 72%, and 46% after elective primary isolated SAVR. Risk of mortality and morbidity after reoperative SAVR has declined and is now similar to that of primary isolated SAVR. Decisions regarding prosthesis choice and SAVR versus transcatheter aortic valve replacement should be made in the context of lifelong disease management rather than avoidance of reoperation.


Gastroprotective effect of nicorandil in indomethacin and alcohol-induced acute ulcers.
Despite the fact that dietary habits and lifestyles are incredibly advancing, gastric ulceration is still a terrible complaint. Extensive use of non-steroidal anti-inflammatory drugs (NSAIDs) and alcohol, in addition to stress, are all predisposing factors for ulcers. Most medical treatments are always time consuming and not efficient or satisfactory to the patients. Cardiovascular patients always need NSAIDs, or mostly cannot quit alcohols, while using many cardiovascular drugs. We aim to study a possible benefit of a common nitrogen oxide donor, anti-anginal drug, nicorandil [N-(2-hydroxyethyl) nicotinamide nitrate ester], in managing acute gastric ulcers through studying its effect on some relevant intermediates to ulcerogenesis as lipid peroxidation, tumor necrosis factor-alpha (TNF-alpha), and nitric oxide (NO). In addition, gastric mucosal histology was studied to pursue the drug effects on tissue level. Our study revealed that both indomethacin and alcohol induced gastric ulcer mainly through up-regulation of gastric mucosal lipid peroxidation, local tissue inflammation, leukocytic infiltration, and necrosis. Both ulcerogens significantly elevated TNF-alpha and decreased NO, initiating ulcer formation. Nicorandil pretreatment depicted a higher preventive index in indomethacin- (89.8%) and alcohol-induced (77.7%) acute ulceration. On the tissue level, it also protected the gastric mucosa combating leukocyte infiltration and tissue congestion. Nicorandil protected tissue necrosis through decreasing oxidative stress, elevating NO levels, and down-regulating the ulcerogen-induced TNF-alpha elevation and improved sub-mucosal blood supply. We conclude that nicorandil may be a suitable bimodal treatment for cardiovascular patients who are at high risk of gastric ulcers by using variable analgesics to alleviate possible cardiac pain episodes, and probably frequent doses will offer a more established and long-lasting protection.


Complete non-proline backbone resonance assignments of the S. aureus neutrophil serine protease inhibitor, EapH1.
The S. aureus extracellular adherence protein (Eap) and its homologs, EapH1 and EapH2, serve roles in evasion of the human innate immune system. EapH1 binds with high-affinity and inhibits the neutrophil azurophilic granule proteases neutrophil elastase, cathepsin-G and proteinase-3. Previous structural studies using X-ray crystallography have shown that EapH1 binds to neutrophil elastase and cathepsin-G using a globally similar binding mode. However, whether the same holds true in solution is unknown and whether the inhibitor experiences dynamic changes following binding remains uncertain. To facilitate solution-phase structural and biochemical studies of EapH1 and its complexes with neutrophil granule proteases, we have characterized EapH1 by multidimensional NMR spectroscopy. Here we report a total of 100% of the non-proline backbone resonance assignments of EapH1 with BMRB accession number 50,304.


Myocardial and microcirculatory kinetics of BR14, a novel third-generation intravenous ultrasound contrast agent.
This study sought to investigate the myocardial and microvascular kinetics of BR14, a novel third-generation ultrasound contrast agent. BR14 produces persistent myocardial opacification after the administration of a single intravenous bolus when the left ventricular cavity contrast has considerably diminished. The mechanism of this finding is unknown. Nine open-chest dogs with non-critical stenosis of a single coronary artery were given intravenous bolus injections of BR14 during coronary hyperemia. Time versus acoustic intensity (AI) plots were generated from the normal and stenosed beds and myocardial blood flow (MBF) was measured with radiolabeled microspheres. Intravital microscopy was performed on an exteriorized cremaster muscle in 11 wild-type mice to study the microvascular kinetics of the agent. At peak contrast enhancement, the ratio between AI in the stenosed and normal bed was 0.44+/-0.23, which was similar to the radiolabeled microsphere-derived MBF ratio between the two beds (0.45 +/-0.20). At 400 s after injection, the AI ratio between the two beds approximated unity (0.99+/-0.07) despite no changes in MBF, indicating redistribution of the agent. The myocardial kinetics of BR14 was best characterized by a modified lagged normal density function. Only about 3% of administered microbubbles were estimated to be retained in the myocardium. Intravital microscopy showed that most of these bubbles were retained only transiently (2 to 3 s) within capillaries. BR14 demonstrates redistribution because of transient retention within capillaries. Therefore, similar to (201)Tl, it could potentially be used to detect both coronary stenosis and myocardial viability after a single injection during stress.


Retracted: Classification of Breast Cancer Images by Implementing Improved DCNN with Artificial Fish School Model.
[This retracts the article DOI: 10.1155/2022/6785707.].


Fractionation of chromosomes. II. Use of hydrophobic affinity partition in aqueous two-phase system.
A simple method for separation of large quantities of isolated metaphase chromosomes in Single-Tube Partition (STP), using hydrophobic ligand in an aqueous two-phase system is presented. The two-phase system is composed of an aqueous solution of Dextran 500 and poly(ethylene) glycol 6000 (PEG). The concentration of chromosomes to be separated has no influence on the distribution behaviour in the partition system and up to 10(7) chromosomes can be used in a phase system as small as 3-5 g (5 ml tube). Different groups of chromosomes differ in their distribution in the two phases and the introduction of PEG with covalently attached hydrophobic ligand provides a means of controlling the distribution of chromosomes. A combination of positively charged trimethylaminomethane PEG (TMA-PEG) together with palmitat PEG (P-PEG) gives a fairly good condition for separating chromosomes on the basis of their net surface charge differences.


Cleaning and sampling protocol for analysis of mercury and dissolved organic matter in freshwater systems.
Mercury (Hg), and in particular its methylated form (methylmercury, MeHg), is a hazardous substance with the potential to produce significant adverse neurological and other health effects. Enhanced anthropogenic emissions and long-range transport of atmospheric Hg have increased Hg concentrations above background levels in aquatic systems. In this context, the Minamata Convention, a global legally binding agreement that seeks to prevent human exposure to Hg, was signed and enforced by 128 countries, and today more than 90 Parties have ratified it. All these Parties have committed to develop Hg monitoring programs to report the effectiveness of the convention. For this purpose, we provide a standardized cleaning and water sampling protocol for the determination of total-Hg and MeHg in freshwaters at ambient levels. As Hg and organic matter are tightly bound, the protocol also describes sample collection for dissolved organic carbon (DOC) concentration and characterization of dissolved organic matter (DOM) composition by fluorescence spectroscopy. This protocol is highly useful to non-experts without a prior background in Hg sampling and analysis, and can serve as a useful basis for national monitoring programs. Furthermore, this protocol should help increase quantitative inventories of DOC, inorganic-Hg (IHg) and MeHg concentrations and DOM composition in freshwater, which are severely lacking at a global scale. •Provides a standardized method to collect water samples for IHg, MeHg, DOC and DOM composition from freshwater ecosystems.


Determination of the 50% and 95% Effective Dose of Remimazolam Combined with Propofol for Intravenous Sedation During Day-Surgery Hysteroscopy.
Remimazolam has demonstrated the potential as a valuable medication for procedural sedation. However, there were some shortcomings for higher doses of remimazolam during hysteroscopy in spite of less frequent adverse events. The aim of this study was to find the 50% and 95% effective dose (ED50 and ED95) of remimazolam when combined with propofol for intravenous sedation during day-surgery hysteroscopy. Patients were randomly assigned evenly (20 per group) to one of five different dosage of remimazolam: group A (0.05mg/kg), group B (0.075mg/kg), group C (0.1mg/kg), group D (0.125mg/kg) or group E (0.15mg/kg). Intravenous injection of sufentanil 0.1µg/kg was administered before sedative medication. Intravenous anesthesia was commenced with remimazolam. Subsequently, propofol was administered at 1mg/kg and maintained at 6mg/kg/h. Success was defined when the patient did not move during cervical dilation, had sufficient sedation as judged by SE <60 and no requirement for rescue doses. The success rate, induce and average dosage of propofol, the induction time, total surgery time, recovery time, and adverse events were recorded. Estimate of ED50 and ED95 with 95% confidence interval (CI) was performed by probit regression. The mean (95% CI) values for ED50 and ED95 of remimazolam in patients were 0.09 (0.08-0.11) mg/kg and 0.21 (0.16-0.35) mg/kg, respectively. There was no difference in the induction time, total surgery time, and recovery time among groups. No serious adverse events occurred in all patients. The dose-response effects of remimazolam were evaluated for intravenous sedation during hysteroscopy. A combination of remimazolam and propofol was recommended to produce stabler sedation, reduce the total dosage and have less effect on cardiovascular and respiratory depression.


Improved duplex RT-PCR assay for differential diagnosis of mixed infection of duck hepatitis A virus type 1 and type 3 in ducklings.
Infection with duck hepatitis A virus (DHAV) causes an acute, rapidly spreading, and fatal disease of young ducklings. DHAV type 1 (DHAV-1) and type 3 (DHAV-3) have been identified in China. In this study, a duplex RT-PCR assay was developed to identify DHAV-1 and DHAV-3 with mixed infection. The method was shown to be high specificity and sensitivity. The minimum detection limit of the method has been determined to be 10pg total RNA templates extracted from duck liver samples or 10² copies viral RNA of DHAV-1 and DHAV-3 respectively. Using the method, from 60 clinical liver samples of 26 duckling flocks in Shandong, Guangdong, Sichuan and Henan provinces of China, 15 (57.7%) flocks were identified as mixed infection of DHAV-1 and DHAV-3, and 9 (34.6%) flocks were DHAV-1 or DHAV-3 single infection. Among them, 38.3% (23/60) of duckling samples were detected as mixed infection of DHAV-1 and DHAV-3, and 48.3% (29/60) of samples were DHAV-1 or DHAV-3 single infection. These results indicated that the improved duplex RT-PCR method provides a rapid and cost-effective laboratory differential diagnosis for mixed infection of DHAV-1 and DHAV-3 in ducklings.


Ketogenic Diet Modulates NAD+-Dependent Enzymes and Reduces DNA Damage in Hippocampus.
The ketogenic diet's (KD) anti-seizure effects have long been documented. Recently, its therapeutic potential in multiple neurodegenerative and neurodevelopmental disorders has emerged. Yet experimental evidence for a fundamental mechanism underlying beneficial effects across numerous diseases remains lacking. We previously showed that feeding rats a KD produced an early (within 2 days) and persistent elevation of hippocampal nicotinamide adenine dinucleotide+ (NAD+), an essential metabolic coenzyme and signaling molecule. NAD+ is a marker of cellular health and a substrate for enzymes implicated in longevity and DNA damage repair such as sirtuins and poly-ADP ribose polymerase-1 (PARP-1). As a result, activation of NAD+-dependent enzymes' downstream pathways could be the origin of KD's broad beneficial effects. Here rats were fed ad libitum regular chow or KD for 2 days or 3 weeks and the levels of hippocampal sirtuins, PARP-1, and the oxidative DNA damage marker 8-hydroxy-2'-deoxyguanosine were quantified. We found a significant immediate and persistent increase in the collective activity of nuclear sirtuin enzymes, and a significant augmentation of Sirt1 mRNA at 2 days. Levels of PARP-1 and 8-hydroxy-2'-deoxyguanosine decreased after 2 days of treatment and further declined at 3 weeks. Our data show that a KD can rapidly modulate energy metabolism by acting on NAD+-dependent enzymes and their downstream pathways. Thus, therapy with a KD can potentially enhance brain health and increase overall healthspan via NAD+-related mechanisms that render cells more resilient against DNA damage and a host of metabolic, epileptic, neurodegenerative, or neurodevelopmental insults.


Hydrogen peroxide release from human eosinophils on fibronectin: scopoletin enhances eosinophil activation.
We have examined the release of H(2)O(2) from PAF or TNFalpha-stimulated human eosinophils on fibronectin (FN)-coated polystyrene plates. H(2)O(2) release was measured by the standard scopoletin-horseradish peroxidase (SCOP-HRP) method and compared with that measured by a new microplate fluorescent assay for H(2)O(2) using a novel HRP substrate A6550. We observed that the SCOP-HRP method gave a 25-fold higher estimate of H(2)O(2) release from eosinophils than did the A6550-HRP method. Microscopic examination of PAF or TNFalpha-stimulated eosinophils in buffer alone or A6550-HRP reaction mixture showed that the cells remained generally round, while eosinophils in SCOP-HRP reaction mixture were spread on the fibronectin-coated surface. Measurement of the cellular ATP content after PAF-stimulation showed that only eosinophils activated in SCOP-HRP had a 50% fall in ATP content. This supported our conclusion that measurement of H(2)O(2) release from eosinophils in SCOP-HRP reaction mixture is problematic since the SCOP-HRP system activates eosinophils. However, we also found that A6550-HRP, when present throughout the incubation, resulted in a lower estimate of H(2)O(2) release than expected. The method used to detect eosinophil H(2)O(2) release greatly influences the absolute amount of H(2)O(2) detected.


A review on arsenic carcinogenesis: Epidemiology, metabolism, genotoxicity and epigenetic changes.
Long-term exposure to arsenic (inorganic arsenic) is a world-wide environmental health concern. Arsenic is classified as the Group 1 human carcinogen by the International Agency for Research on Cancer (IARC). Epidemiological studies have established a strong association between inorganic arsenic (iAs) exposure in drinking water and an increased incidence of cancer including bladder, liver, lung, prostate, and skin cancer. iAs also increases the risk of other diseases such as cardiovascular disease, hypertension and diabetes. The molecular mechanisms of carcinogenesis of iAs remain poorly defined, several mechanisms have been proposed, including genotoxicity, altered cell proliferation, oxidative stress, changes to the epigenome, disturbances of signal transduction pathways, cytotoxicity and regenerative proliferation. In this article, we will summarize current knowledge on the mechanisms of arsenic carcinogenesis and focus on integrating all these issues to garner a broader perspective.


The Expression Levels of Genes Responsible for the Enzymatic Activity of Bile Salt Hydrolase (BSH) and the Relationship of Cholesterol Assimilation in L. plantarum and L. paracasei.
The bile salt hydrolase (BSH) activity is responsible for the cholesterol-lowering effect of the probiotic strains. The present study aimed to investigate the relationship between bsh gene-expression (GE) levels responsible for the BSH activity and the parameters of bile salt resistance of different Lactobacillaceae species. Accordingly, 11 Lactobacillaceae family strains with high cholesterol assimilation ratio (49.21-68.22%) determined by the o-phthalaldehyde method selected from 46 Lactobacillaceae species was evaluated for their features including acid tolerance, bile tolerance, and BSH activity. All tested strains survived at pH 2 medium and 0.3% (w/v) bile salt and showed positive BSH activity for glycocholic acid (GCA) and taurocholic acid (TCA). BSH gene expression was performed to provide clear information and to identify the key genes responsible for BSH activity. bsh3 genes were found highest GE level (P < 0.05) in Lactiplantibacillus plantarum and Lacticaseibacillus paracasei strains. The results showed that high cholesterol assimilation ratio were closely correlated with BSH activity and the parameters of bile salt resistance. The results of this study will support the development of a new approach based on phenotypic and genetic analysis to determine the bile salt parameters. The study will be useful for the selection of Lactobacillus strains with high bile salt resistance.


Photochemical reactivity of nitrogen-doped biochars under simulated sunlight irradiation: Generation of singlet oxygen.
This study explored the photochemical activity of nitrogen-doped biochars (NCMs) by investigating their role in the degradation of sulfamethazine under simulated sunlight irradiation. NCMs with different doping amounts were prepared from corn straw and urea. Results showed that nitrogen doping can notably enhance the photodegradation of SMT rather than raw char. NCMs are of photochemical activity under visible light, which was confirmed by monochromatic light experiments. Quenching experiments, ESR, pH effect, and the influence of O2 were carried out to explore the involved oxidation mechanism in this system. Results showed that 1O2 was the main reactive oxygen species. 1O2 was produced from O2 by both energy transfer and electron transfer. DFT calculations showed that pyridinic N doping can decrease the energy of intersystem crossing and thus benefit the generation of 1O2 by triplet-triplet energy transfer. Results underscore the explicit importance of nitrogen element in photochemical reactivity of chars under simulated light irradiation even when the nitrogen content is low. It is a meaningful reminder for us to pay more attention to the assessment of the fate and transport of contaminants in the soil where it is rich in NCMs as well as the potential use of NCMs for pollutants remediation, since visible light is very abundant near the earth's surface.


Male sterility in triploid dandelions: asexual females vs. asexual hermaphrodites.
Male reproductive output, pollen in plants and sperm in animals has been shown to constitute a substantial cost for many organisms. In parthenogenetic hermaphrodites, selection is therefore expected to reduce the allocation of resources to male reproductive output. However, sustained production of pollen or sperm has been observed in numerous asexual hermaphrodites. We studied the widespread production of pollen by triploid asexual dandelions, Taraxacum sect. Ruderalia, comparing rare male sterile individuals with pollen producing asexuals. We found that individuals can show plasticity in the production of pollen, but that it is nevertheless possible to distinguish between (facultatively) male sterile asexuals and male fertile asexuals. Based on evidence from genetic markers and crosses, we conclude that the male sterility in asexual dandelions is caused by nuclear genes, in contrast to the cytoplasmically inherited male sterility previously found in sexual dandelions. Male sterile lineages did not produce more seeds per flower head, heavier seeds or seeds that were more viable. However, male sterile plants did produce more seed heads and hence more seeds than pollen producing ones, indicating that they were able to reallocate resources toward seed production. Considering the difference in seed production, it remains puzzling that not more asexual dandelions are male sterile.


Dinuclear platinum(II) complexes as the pattern for phosphate backbone binding: a new perspective for recognition of binding modes to DNA.
The mechanism of action of most approved drugs in use today is based on their binding to specific proteins or DNA. One of the achievements of this research is a new perspective for recognition of binding modes to DNA by monitoring of changes in measured and stoichiometric values of absorbance at 260 nm. UV-Vis and IR spectroscopy, gel electrophoresis and docking study were used for investigation of binding properties of three dinuclear platinum(II) complexes containing different pyridine-based bridging ligands, [{Pt(en)Cl}2(μ-4,4'-bipy)]Cl2·2H2O (Pt1), [{Pt(en)Cl}2(μ-bpa)]Cl2·4H2O (Pt2) and [{Pt(en)Cl}2(μ-bpe)]Cl2·4H2O (Pt3) to DNA (4,4'-bipy, bpa and bpe are 4,4'-bipyridine, 1,2-bis(4-pyridyl)ethane and 1,2-bis(4-pyridyl)ethene, respectively). In contrast to the system with well-known intercalated ligand (EtBr), covalently bound ligand (cis-Pt) and with minor groove binder (Hoechst 33258), which do not have significant differences in measured and stoichiometric values, the most pronounced deviations are recorded for two dinuclear platinum(II) complexes (Pt1 and Pt2), as a consequence of complex binding to the phosphate backbone and bending of DNA helix. The hydrolysis of complexes and changes in DNA conformation were also analysed as phenomena that may have an impact on the changes in absorbance.


Second workers' compensation claims: who is at risk? Analysis of WorkSafe Victoria, Australia compensation claims.
To determine the risk factors associated with early repeat workers' compensation claims in Victoria, Australia and to compare our findings with those of a study on the Alberta's Workers' Compensation Board (WCB) in Canada. We reviewed and described 178,630 claims from 1996-2009. Both persons with single and persons with multiple claims were included. Survival analysis was used to determine the impact of socio-demographic factors on the time between claims. A total of 37% of persons with an initial claim lodged a second claim. A reduced time to a second claim was observed in younger males in the manufacturing industry. Earlier second claims were more common in workers exposed to mental stress, sound and pressure, or chemical and other substances. These findings are similar to those of WCB Alberta. There is a potential to reduce the socio-economic burden of workplace injury in both jurisdictions by enacting prevention programs targeted at workers with an increased risk of repeat claims.


Oncologic safety of breast conserving surgery after tumour downsizing by neoadjuvant therapy: a retrospective single centre cohort study.
The objective of this study is to analyse local recurrence rates in patients receiving neoadjuvant chemotherapy (nCT) comparing mastecomized (MX) patients with those undergoing breast conserving therapy (BCT). Patients undergoing breast cancer surgery after nCT (3xCMF or 3-6xED) between 1995 and 2007 at our department were retrospectively analysed. The median follow up was 60 months for 308 patients. Patients who were downsized from MX to BCT with partial or complete response (n = 104) had a similar local recurrence free survival (LRFS) compared to patients who did not experience successful downsizing (n = 67) and finally undergoing MX (LRFS MX-BCT 81% vs. MX-MX 91%; P = 0.79). Uni- and multivariate analyses demonstrated that BCT itself was not an independent prognostic factor for a worse LRFS (P = 0.07 and 0.14). After no pathologic change or progressive disease the risk of local recurrence was increased in patients undergoing BCT (MX-BCT; n = 6 LRFS 66%) compared with MX (n = 44; LRFS 90%; P = 0.04). Overall survival in general was better for the BCT group (n = 197) compared with MX group (n = 111) regardless of clinical response (92% vs. 72%; P < 0.0001). Breast conservation, nodal negativity and low or medium grade histology were prognostic factors for an improved OS (P = 0.02, 0.01, 0.004). In conclusion, our study suggests that BCT is oncologically safe after tumour downsizing by nCT in patients primarily scheduled for mastectomy. These patients, however, should not be treated with breast conservation in the absence of any proven response after nCT.


Body Mass Index and Revision Total Knee Arthroplasty: Does Cause for Revision Vary by Underweight or Obese Status?
Body mass index (BMI) impacts risk for revision total knee arthroplasty (rTKA), but the relationship between BMI and cause for revision remains unclear. We hypothesized that patients in different BMI classes would have disparate risk for causes of rTKA. There were 171,856 patients who underwent rTKA from 2006 to 2020 from a national database. Patients were classified as underweight (BMI < 19), normal-weight, overweight/obese (BMI 25 to 39.9), or morbidly obese (BMI > 40). Multivariable logistic regressions adjusted for age, sex, race/ethnicity, socioeconomic status, payer status, hospital geographic setting, and comorbidities were used to examine the effect of BMI on risk for different rTKA causes. Compared to normal-weight controls, underweight patients were 62% less likely to undergo revision due to aseptic loosening, 40% less likely due to mechanical complications, 187% more likely due to periprosthetic fracture, 135% more likely due to periprosthetic joint infection (PJI). Overweight/obese patients were 25% more likely to undergo revision due to aseptic loosening, 9% more likely due to mechanical complications, 17% less likely due to periprosthetic fracture, and 24% less likely due to PJI. Morbidly obese patients were 20% more likely to undergo revision due to aseptic loosening, 5% more likely due to mechanical complications, and 6% less likely due to PJI. Mechanical reasons were more likely to be the cause of rTKA in overweight/obese and morbidly obese patients, compared to underweight patients, for whom revision was more likely to be infection or fracture related. Increased awareness of these differences may promote patient-specific management to reduce complications. III.


Bioconversion of biomass waste into high value chemicals.
Dwindling petroleum resources and increasing environmental concerns have stimulated the production of platform chemicals via biochemical processes through the use of renewable carbon sources. Various types of biomass wastes, which are biodegradable and vastly underutilized, are generated worldwide in huge quantities. They contain diverse chemical constituents, which may serve as starting points for the manufacture of a wide range of valuable bio-derived platform chemicals, intermediates, or end products via different conversion pathways. The valorization of inexpensive, abundantly available, and renewable biomass waste could provide significant benefits in response to increasing fossil fuel demands and manufacturing costs, as well as emerging environmental concerns. This review explores the potential for the use of available biomass waste to produce important chemicals, such as monosaccharides, oligosaccharides, biofuels, bioactive molecules, nanocellulose, and lignin, with a focus on commercially viable technologies.


American paternal age data for selected years from 1876 to 1981.
For selected years in the time span of 1876 through 1981, mean average paternal ages are itemized and the methods for the calculation of these figures are illustrated. For this time period, mean average paternal ages dropped from a high of 36.9 years to 28.5 years in 1981. This change was accounted for by an absolute and relative decrease in the number of births to older fathers and by an absolute and relative increase in births to younger fathers.


Effect of ultrafine grain on tensile behaviour and corrosion resistance of the duplex stainless steel.
The ultrafine grained 2205 duplex stainless steel was obtained by cold rolling and annealing. The tensile properties were investigated at room temperature. Comparing with coarse grained stainless steel, ultrafine grained sample showed higher strength and plasticity. In addition, grain size changed deformation orientation. The strain induced α'-martensite was observed in coarse grained 2205 duplex stainless steel with large strain. However, the grain refinement inhibited the transformation of α'-martensite;nevertheless, more deformation twins improved the strength and plasticity of ultrafine grained 2205 duplex stainless steel. In addition, the grain refinement improved corrosion resistance of the 2205 duplex stainless steel in sodium chloride solution.


Epithelial and endothelial barriers in the olfactory region of the nasal cavity of the rat.
The olfactory ensheathing (glial) cells (OECs) have been identified to be useful candidate cells to support regeneration after being transplanted into injured fiber tracts of the central nervous system. We investigated by means of immunocytochemistry and freeze-fracturing the morphology and molecular composition of OEC tight junctions in the rat olfactory system. In addition, we tested the hypothesis whether tight junctions and orthogonal arrays of particles (OAPs) which contain the water channel protein aquaporin-4 (AQP4), are mutually exclusive as suggested in previous studies. In OECs, we found neither OAPs nor AQP4, but tight junctions immunoreactive for ZO-1, occludin, and claudin-5, but immunonegative for ZO-2 and claudin-3. To shed more light on the function of OEC tight junctions, we tested the permeability and tight junction composition of blood vessels and fila olfactoria. We found them both, permeable for infused lanthanum nitrate, and to be immunopositive for ZO-1 and claudin-5. The tight junctions of the OECs are discussed to be responsible for micro-compartmentalization within the olfactory fiber tract providing a benefit for axonal growth.


Cobalt bis(acetylacetonate)-tert-butyl hydroperoxide-triethylsilane: a general reagent combination for the Markovnikov-selective hydrofunctionalization of alkenes by hydrogen atom transfer.
We show that cobalt bis(acetylacetonate) [Co(acac)2], tert-butyl hydroperoxide (TBHP), and triethylsilane (Et3SiH) constitute an inexpensive, general, and practical reagent combination to initiate a broad range of Markovnikov-selective alkene hydrofunctionalization reactions. These transformations are believed to proceed by cobalt-mediated hydrogen atom transfer (HAT) to the alkene substrate, followed by interception of the resulting alkyl radical intermediate with a SOMOphile. In addition, we report the first reductive couplings of unactivated alkenes and aryldiazonium salts by an HAT pathway. The simplicity and generality of the Co(acac)2-TBHP-Et3SiH reagent combination suggests it as a useful starting point to develop HAT reactions in complex settings.


Cardiac transplantation at the Texas Heart Institute: comparative analysis of two groups of patients (1968-1969 and 1982-1983).
Two groups of heart transplant recipients were studied. Patients in Group 1 underwent heart transplantation from May, 1968, to November, 1969. They were compared with Group 2, a series begun in July, 1982, when the current cardiac transplantation program was renewed at the Texas Heart Institute, and terminated in December, 1983. Patient selection, management, and results were compared. With a cumulative follow-up of 64 patient-months (Group 1) versus 93 patient-months (Group 2), the actuarial 18-month survival was 0 in Group 1 versus 70% in Group 2. Nine of the 18 patients in Group 1 died of rejection versus 4 of the 18 patients in Group 2. There were 6 infection-related deaths in Group 1 and none in Group 2. Using linearized rates based on 100 patient-months, the incidences of rejection and infection were, respectively, 23 versus 10.7 (p less than 0.05) and 64 versus 34 (p less than 0.05) between Groups 1 and 2. Incidence, pattern, and severity of these major complications have been reduced significantly. Over the last decade, there have been improvements in the selection of potential candidates, better management of donors, improved graft preservation, and the introduction of more selective immunosuppression.


Reduced expression and activation of voltage-gated sodium channels contributes to blunted baroreflex sensitivity in heart failure rats.
Voltage-gated sodium (Na(v)) channels are responsible for initiation and propagation of action potential in the neurons. To explore the mechanisms of chronic heart failure (CHF)-induced baroreflex dysfunction, we measured the expression and current density of Na(v) channel subunits (Na(v)1.7, Na(v)1.8, and Na(v)1.9) in the aortic baroreceptor neurons and investigated the role of Na(v) channels in aortic baroreceptor neuron excitability and baroreflex sensitivity in sham and CHF rats. CHF was induced by left coronary artery ligation. The development of CHF (6-8 weeks after the coronary ligation) was confirmed by hemodynamic and morphological characteristics. Immunofluorescent data indicated that Na(v)1.7 was expressed in A-type (myelinated) and C-type (unmyelinated) nodose neurons, but Na(v)1.8 and Na(v)1.9 were expressed only in C-type nodose neurons. Real-time RT-PCR and Western blot data showed that CHF reduced mRNA and protein expression levels of Na(v) channels in nodose neurons. In addition, using the whole-cell patch-clamp technique, we found that Na(v) current density and cell excitability of the aortic baroreceptor neurons were lower in CHF rats than that in sham rats. Aortic baroreflex sensitivity was blunted in anesthetized CHF rats, compared with that in sham rats. Furthermore, Na(v) channel activator (rATX II, 100 nM) significantly enhanced Na(v) current density and cell excitability of aortic baroreceptor neurons and improved aortic baroreflex sensitivity in CHF rats. These results suggest that reduced expression and activation of the Na(v) channels are involved in the attenuation of baroreceptor neuron excitability, which subsequently contributes to the impairment of baroreflex in CHF state.


Effect of Cr (III) on hydration, microstructure of magnesium phosphate cement, and leaching toxicity evaluation.
The pollution caused by chromium and its compounds has caused severe harm to the environment, and waste stabilization/solidification containing these contaminants by magnesium phosphate cement (MPC) is one of the best ways to address this problem. If the mechanism between Cr3+ and MPC can be understood, it will significantly improve the latter's solidification performance with respect to ameliorating Cr pollution. In this paper, the compressive strength, microstructure, pH in the process of sample hydration, and leaching toxicity of solidified forms were studied by adding various amounts of Cr3+ into MPC. The setting time of MPC decreased at first and then increased as the Cr3+ concentration increased. The added Cr3+ reacted with the phosphate ions to form mineral phases, which changed the MPC matrix structure. The matrix's compressive strength was higher when the M/P ratio (MgO/KH2PO4 mass ratio) was smaller. When the concentration of Cr3+ was constant, and the M/P ratio was low (< 4:1), the matrix's compressive strength increased as the M/P ratio increased. The presence of Cr3+ changed the system's pH and affected the hydration products' morphology; this trend strengthened as the Cr3+ concentration increased. The highest leaching concentration of Cr3+ was 0.255 mg/L, and the concentration decreased as the M/P ratio decreased. During solidification, the appropriate proportion of MPC can be selected according to the concentration of Cr3+ to achieve better solidification performance.


[Mammary duct ectasia in children: A case report].
Bloody nipple discharge is an infrequent symptom during childhood. The most common cause in this population is mammary duct ectasia (MDE), which is a benign and self-limiting condition, that is characterized by dilatation of the mammary ducts, fibrosis and periductal inflammation. Report of a case of MDE in order to improve physicians' diagnosis accuracy and avoid aggressive studies and treatments. Six-months old male healthy infant, exclusively breastfeeded, that visited our clinic with a lump beneath his right nipple and bloody discharge from the same nipple. An ultrasound was performed which showed a multicystic lesion suggestive of MDE. Watchful waiting was decided as treatment, with good evolution after six months of follow up. The MDE is the leading cause of bloody discharge in pediatric population, being a benign condition that resolves spontaneously before nine months. The knowledge of this condition is essential so as to accurately diagnose and treat it.


Monosomy 7 in two patients with a myeloproliferative disorder.
Clinical and laboratory data are presented for two patients with a dyshaematopoietic disorder, and monosomy 7 in their bone marrow cells. The first patient, a 55-year-old woman, had been treated with chlorambucil for an ovarian carcinoma. After 4 years an oligoblastic myeloid leukaemia was diagnosed and she later died with an acute transformation of the disease. The second patient, a 21-year-old male, has had a dyserythropoietic anaemia with transient pancytopenia for over 5 years without any signs of malignancy. The possible relationship between therapy, the monosomy 7 and the other bone marrow abnormalities is briefly discussed. From an analysis of the data of these and comparable cases in the literature it appears that loss of chromosome No. 7 material is often associated with erythropoietic disorders such as erythroid hyperplasia and erythraemia. The reduction or absence of the Colton blood group antigens found in our patients and in a few other monosomy 7 cases also points to an abnormality of the red cell line.


Intraoperative radiotherapy in the multimodality approach to gastric cancer.
It is difficult to conclude a clear benefit from the addition of IORT to the multimodality treatment of gastric cancer based on the studies available. Only three prospective randomized trials have been published and each varies in the approach of combining adjuvant and neoadjuvant chemotherapy and EBRT with IORT. With a complex degree of confounding factors in these and other retrospective series, it also remains difficult to identify a decrease in local recurrence rates, or an improvement in overall patient survival rates attributable to the use of IORT. Several series, however, have identified patient subsets--specifically, patients who have advanced disease with serosal extension or node-positive disease--who may be more likely to benefit from the addition of IORT to gastric resection. Finally, there is no evidence in prospective or retrospective series that there is an increased patient risk or inferior outcome caused by the addition of IORT. Limited evidence of a possible benefit in advanced disease and no evidence of a disadvantage to the use of IORT have promoted continued use and investigation in the multimodality treatment of an aggressive disease. Continued efforts in prospective randomized trials should be promoted to further delineate the efficacy of IORT and EBRT in the treatment of gastric cancer, especially in light of recently published data [30], where concurrent chemotherapy has been reported to increase survival rates in high-risk patients.


Left atrial remodeling, early repolarization pattern, and inflammatory cytokines in professional soccer players.
Although regular physical exercise clearly reduces cardiovascular morbidity risk, long-term endurance sports practice has been recognized as a risk factor for atrial fibrillation (AF). However, the mechanisms how endurance sports can lead to AF are not yet clear. The aim of our present study was to investigate the influence of long-term endurance training on vagal tone, atrial size, and inflammatory profile in professional elite soccer players. A total of 25 professional major league soccer players (mean age 24±4 years) and 20 sedentary controls (mean age 26±3 years) were included in the study and consecutively examined. All subjects underwent a sports cardiology check-up with physical examination, electrocardiography, echocardiography, exercise testing on a bicycle ergometer, and laboratory analysis [standard laboratory and cytokine profile: interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-8, IL-10]. Athletes were divided into two groups according to presence or absence of an early repolarization (ER) pattern, defined as a ST-segment elevation at the J-point (STE) ≥0.1mm in 2 leads. Athletes with an ER pattern showed significantly lower heart rate and an increased E/e' ratio compared to athletes without an ER pattern. STE significantly correlated with E/e' ratio as well as with left atrial (LA) volume. The pro-inflammatory cytokines IL-6, IL-8, TNF-α as well as the anti-inflammatory cytokine IL-10 were significantly elevated in all soccer players. However, athletes with an ER pattern had significantly higher IL-6 plasma levels than athletes without ER pattern. Furthermore, athletes with "high" level IL-6 had significantly larger LA volumes than players with "low" level IL-6. Athletes with an ER pattern had significantly higher E/e' ratios, reflecting higher atrial filling pressures, higher LA volume, and higher IL-6 plasma levels. All these factors may contribute to atrial remodeling over time and thus increase the risk of AF in long-term endurance sports.


The normal jugular spur, jugular foramen, and jugular bulb as visualized on skull and temporal bone radiographs.
Special jugular foramen views or tomography are generally used to radiographically delineate the jugular spur, jugular fossa, and jugular foramen. Details of this area are not ordinarily searched for by the radiologist on skull films nor otoroentgen views of the temporal bone for various reasons: attention to certain small "key-areas," rectilinear distortion, superimposition of neighboring structures, radiodensity of the petrous pyramid, etc. This paper outlines the radiographic anatomy of the jugular area and details its appearance on plain skull films (AP, PA, and submentovertical projections) and on special views of the temporal bone (Schuller's, Owen's, Mayer's, Stenvers', Low-Beer's).


Role of ELK1 in regulating colorectal cancer progression: miR-31-5p/CDIP1 axis in CRC pathogenesis.
Colorectal cancer (CRC) is a malignant tumor that affects the digestive system. With the increased of modernization of society, the incidence of colorectal cancer has increased throughout the world. As a transcription factor, ELK1 has been widely studied in colorectal cancer. However, there are still many unknown factors regarding its specific mechanism of action.This study explored the role of ELK1 and its downstream pathway in CRC pathogenesis. Based on clinical samples, this study examined miR-31-5p expression in CRC cells and its impact on malignant behaviors (migration, invasion, apoptosis) and autophagy. The promoter sequence of miR-31-5p was obtained from the UCSC database, and ELK1 was identified as its transcription factor. In ELK1-knockdown CRC cells, miR-31-5p was overexpressed, and its response in malignant behaviors and autophagy was analyzed. The target gene CDIP1 was predicted and verified using a dual-luciferase assay. The influence of CDIP1 on malignant behavior in CRC cells was assessed, and CDIP1 siRNA was used as a rescue treatment for miR-31-5p inhibition. The role of ELK1/miR-31-5p in tumor growth was validated in vivo. miR-31-5p expression was upregulated in the colorectal cancer tissues and cells. The knockdown of miR-31-5p markedly inhibited cancer cells' malignant behaviors and mediated autophagy. ELK1 was confirmed to bind with the miR-31-5p promoter and enhance miR-31-5p transcription. miR-31-5p was found to bind with the CDIP1 3'UTR and inhibit CDIP1 expression. CDIP1 siRNA partially rescued the effects of miR-31-5p knockdown on cell metastatic ability, autophagy, and apoptosis. Based on the in vivo experiments, results showed that the ELK1/miR-31-5p axis positively regulated tumor growth in nude mice. Our findings indicate that ELK1 regulates the progression of colorectal cancer via an miR-31-5p/CDIP1 axis, and the ELK1/miR-31-5p/CDIP1 axis could be a therapeutic target for colorectal cancer.


Procedural results and in-hospital outcomes of percutaneous coronary intervention for chronic total occlusion in patients with reduced left ventricular ejection fraction: Sub-analysis of the Japanese CTO-PCI Expert Registry.
To evaluate the procedural results and in-hospital outcomes of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) in patients with reduced left ventricular ejection fraction (LVEF). While the technical success of general CTO-PCI has improved, CTO-PCI patients with reduced LVEF remain at high-risk for adverse events. The data of 820 patients with LVEF ≤ 35% (Group 1), 1816 patients with LVEF = 35%-50% (Group 2), and 5503 patients with LVEF ≥ 50% (Group 3), registered in the Japanese CTO-PCI Expert Registry from January 2014 to December 2019, were retrospectively analyzed. The primary endpoint was in-hospital major adverse cardiac or cerebrovascular events (MACCEs), including death, myocardial infarction, stent thrombosis, stroke, and emergent revascularization. Secondary endpoints included procedural details, guidewire success, and technical success. There were no differences in guidewire and technical success rates between the groups. In-hospital MACCEs was significantly higher in Group 1 (Group 1 vs. Group 2 vs. Group 3: 3.4% vs. 1.7% vs. 1.5%, p = 0.001) and was especially driven by death (1.3% vs. 0.3% vs. 0.1%, p < 0.001) and stroke (0.7% vs. 0.2% vs. 0.2%, p = 0.007). Multivariate analysis showed that LVEF ≤ 35% (odds ratio [OR]; 1.58, 95% confidence interval [CI]; 1.04-2.41, p = 0.03) and New York Heart Association (NYHA) class ≥ 3 (OR; 2.01, 95% CI; 1.03-3.93, p = 0.04) were predictors of in-hospital MACCEs. In-hospital MACCEs were significantly higher in patients with LVEF ≤ 35%. LVEF ≤;35% and NYHA class ≥ 3 were predictors of in-hospital MACCEs after CTO-PCI.


RUNX3 protein is overexpressed in human epithelial ovarian cancer.
RUNX family genes, including RUNX3, are developmental regulators that are important in human cancers. The purpose of this study was to evaluate expression and oncogenic potential of RUNX3 in ovarian carcinoma. Immunohistochemical staining was performed on 60 malignant, 14 borderline, and 5 normal ovarian specimens. Correlation between RUNX3 expression with tumor histology was performed. RUNX3 expression was evaluated by quantitative real-time polymerase chain reaction (QRT-PCR) in microdissected normal and malignant epithelial ovarian tissues. Cell proliferation and viability studies were performed on cells expressing RUNX3 by lentiviral infection and cells with silenced RUNX3 expression by siRNA. RUNX3 expression by immunohistochemistry was higher in serous ovarian carcinomas versus normal ovarian epithelium (P<0.001). Immunofluorescent staining confirmed upregulation of cytoplasmic RUNX3 in ovarian cancer cell lines and tissues. QRT-PCR showed higher RUNX3 mRNA expression in microdissected borderline and malignant ovarian tumor tissues compared with the normal ovarian surface epithelial cells (HOSE) (P=0.006 and P=0.023). Forced RUNX3 expression by lentiviral gene delivery in ovarian cancer cells, SKOV3, that initially showed undetectable RUNX3 expression, resulted in increased cell viability (P=0.043). Silencing RUNX3 expression by siRNA transfection into ovarian cancer cells, OVCAR429, initially expressing high levels of endogenous RUNX3 resulted in a decrease in proliferation (P=0.021). These results suggest that RUNX3 has a role in cell proliferation and viability in ovarian cancer.


Small Bowel Congenital Anomalies: a Review and Update.
The small intestine is a complex organ system that is vital to the life of the individual. There are a number of congenital anomalies that occur and present most commonly in infancy; however, some may not present until adulthood. Most congenital anomalies of the small intestine will present with obstructive symptoms while some may present with vomiting, abdominal pain, and/or gastrointestinal bleeding. Various radiologic procedures can aid in the diagnosis of these lesions that vary depending on the particular anomaly. Definitive therapy for these congenial anomalies is surgical, and in some cases, surgery needs to be performed urgently. The overall prognosis of congenital anomalies of the small intestine is very good and has improved with improved medical management and the advent of newer surgical modalities. The congenital anomalies of the small intestine reviewed in this article include malrotation, Meckel's diverticulum, duodenal web, duodenal atresia, jejunoileal atresia, and duplications.


Aspirin desensitization in patients undergoing percutaneous coronary interventions with stent implantation.
The aim of this study was to test the safety and efficacy of a novel rapid desensitization procedure in patients with acetylsalicylic acid sensitivity and coronary artery disease who underwent cardiac catheterization and coronary stent implantation. Aspirin plays a key role in the secondary prevention of atherothrombotic events and thrombotic complications after stent implantation. Aspirin sensitivity not only limits patients to benefit from the long-term use of this antiplatelet agent but is also often an impediment to the implantation of bare-metal and drug-eluting coronary stents. Of 1,014 patients admitted for cardiac catheterization, 26 (2.6%) had histories of aspirin sensitivity characterized by respiratory or cutaneous manifestations (none had previous anaphylactic reactions); of these, 61.5% presented with acute coronary syndromes. All patients underwent a novel rapid desensitization challenge procedure before cardiac catheterization, except for those presenting with ST-elevation myocardial infarctions (n = 4), who underwent desensitization before hospital discharge. The desensitization procedure involved the oral administration of 6 sequential doses of aspirin (1, 5, 10, 20, 40, and 100 mg) over 5.5 hours without the use of corticosteroids or antihistamines. Patients were followed for 1 year to assess compliance with aspirin therapy and adverse events. The desensitization procedure was successful in 23 patients (88.5%). Percutaneous coronary intervention with stent implantation was performed in 22 patients (1.8 stents/patient). Drug-eluting stents were used in all patients except those who underwent primary percutaneous coronary intervention (n = 3), in whom bare-metal stents were used. Multivessel percutaneous coronary intervention was performed in 30.7% of patients. At follow-up, all patients who successfully responded to the desensitization procedure tolerated aspirin well, without developing allergic reactions. Aspirin was withdrawn in only 1 patient, because of a peptic ulcer. In conclusion, rapid desensitization is safe and highly effective in patients with aspirin sensitivity and coronary artery disease who undergo coronary stent implantation, including those who receive drug-eluting stents.


Influence of salt addition to stimulating biopolymers production in aerobic granular sludge systems.
The influence of salt addition to stimulating biopolymers production in aerobic granular sludge (AGS) systems was evaluated. The control systems (R1: acetate and R2: propionate) initially obtained less accumulation of mixed liquor volatile suspended solids (MLVSS), indicating that the osmotic pressure in the salt-supplemented systems (R3: acetate and R4: propionate) contributed to biomass growth. However, the salt-supplemented systems collapsed between days 110 and 130 of operation. R3 and R4 showed better performance regarding nutrients removal due to the greater abundance of nitrifying and denitrifying bacteria and phosphate-accumulating organisms. Salt also contributed to the higher production of biopolymers such as alginate-like exopolymers (ALE) per gram of volatile suspended solids (VSS) (R1: 397 mgALE∙gVSS-1, R2: 140 mgALE∙gVSS-1, R3: 483 mgALE∙gVSS-1, R4: 311 mgALE∙gVSS-1). Amino acids like tyrosine and tryptophan were better identified in extracellular polymeric substances extract from salt-operated reactors. This study brings important results in the context of resource recovery by treating saline effluents.


Glutamate Receptors Mediate Changes to Dendritic Mitochondria in Neurons Grown on Stiff Substrates.
The stiffness of brain tissue changes during development and disease. These changes can affect neuronal morphology, specifically dendritic arborization. We previously reported that N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors regulate dendrite number and branching in a manner that is dependent on substrate stiffness. Since mitochondria affect the shape of dendrites, in this study, we determined whether the stiffness of substrates on which rat hippocampal neurons are grown affects mitochondrial characteristics and if glutamate receptors mediate the effects of substrate stiffness. Dendritic mitochondria are small, short, simple, and scarce in neurons cultured on substrates of 0.5 kPa stiffness. In contrast, dendritic mitochondria are large, long, complex, and low in number in neurons grown on substrates of 4 kPa stiffness. Dendritic mitochondria of neurons cultured on glass are high in number and small with complex shapes. Treatment of neurons grown on the stiffer gels or glass with the NMDA and AMPA receptor antagonists, 2-amino-5-phosphonopentanoic acid and 6-cyano-7-nitroquinoxaline-2,3-dione, respectively, results in mitochondrial characteristics of neurons grown on the softer substrate. These results suggest that glutamate receptors play important roles in regulating both mitochondrial morphology and dendritic arborization in response to substrate stiffness.


Onset of neural function in the lateral line.
The development of the nervous system includes the formation of specific neuronal connections. Some insight into the mechanisms by which these connections are made may be obtained by determining the order in which the elements of a developing system begin to function and examining any changes that may occur in the system shortly after it begins functioning. I have investigated the lateral line of the South African clawed frog, Xenopus laevis and I have classified the afferent system into three elements. First, the transduction mechanism, which includes all components that couple the water vibrations to the release of transmitter from the hair cell. Second, the afferent synapse, at which there is transmitter release and subsequent postsynaptic conductance changes. And third, the afferent axon. I report here experiments suggesting that these elements become functional in the following order: first, the axon can conduct action potentials; second, transmission is established; third, the transduction mechanism can modulate transmitter release. This same sequence has been reported in a system related to the lateral line, the auditory pathway of mammals.


Intracellularly truncated human alpha2B-adrenoceptors: stable and functional GPCRs for structural studies.
All three alpha2-adrenoceptor subtypes have a long third intracellular loop (3i), which is conserved by overall size and charge-hydrophobic properties but not by amino acid sequence similarity. These properties must be relevant for function and structure, because they have been preserved during hundreds of millions of years of evolution. The contribution of different loop portions to agonist/antagonist binding properties and G protein coupling of the human alpha2B-adrenoceptor (alpha2B-AR) was investigated with a series of 3i truncated constructs (delta3i). We used a variety of agonists/antagonists in competition binding assays. We stimulated alpha2B-AR delta3i with various agonists and measured [35S]GTPgammaS binding in isolated cell membranes with or without antagonist inhibition. We also evaluated the ability of oligopeptides, analogous to the amino and carboxyl terminal parts of 3i, to promote G protein activation, monitored with the [35S]GTPgammaS assay. Our results reveal that the carboxyl end residues of 3i, R360(6.24) to V372(6.36), are important for Gi/Go protein activation. Deletions in regions from G206(5.72) to R245(5.110) altered the binding of some alpha2B-AR agonists, indicating that agonist binding is dependent on the conformation of the 3i domain, possibly through the involvement of G protein interactions. The truncated receptor constructs may be more stable on purification and thus be useful for structural characterization of alpha2B-AR.


Adaptation of a neutrophilic dairy-associated Bacillus cereus isolate to alkaline pH.
This study identified and studied the response of five Bacillus strains, isolated from alkaline cleaning in place (CIP) solutions, to alkaline conditions. Isolates were identified as B. cereus by 16S rDNA sequencing. External and internal cell pH and buffering capacity data of a representative strain, Bacillus DL5, were compared to B. cereus ATCC 10702. Results indicated that a buffering system was induced when the pH of the growth medium increased to above pH 10, which was effective up to pH 12 and presumably cell wall associated. Volume measurements and confocal scanning laser microscope images of Bacillus DL5 cells showed that cells exhibited more pronounced stress symptoms when exposed to pH 10 than at pHs above 10. Long-term exposure of Bacillus DL5 to pH 10 or 10.5 indicated that cells grew in planktonic form and formed biofilms at both pHs. Bacillus DL5 was a neutrophile with a growth pH range similar to B. cereus ATCC 10702, but tolerated alkaline pH. This may be a general trait of the B. cereus species rather than a specific phenomenon of isolates from alkaline ecosystems. Other neutrophilic B. cereus isolates may exhibit similar responses to alkaline conditions as the isolates studied here. These results may have important implications for dairy manufacturers.


Decreased secretory transport of a quarternary ammonium, TBuMA, across LLC-PK1 cells by the anionic kidney extract.
The effect of organic anionic (OA) fractions of various rat organ tissues on the apparent partition coefficients (APC) of quarternary ammoniums (QAs) between n-octanol and phosphate buffer (pH 7.4) and QAs transport across the LLC-PK1 cell monolayer was examined. The OA fraction was prepared by filtering the aqueous extract of each tissue through an ion-exchange cartridge (Bond Elut C18). In the presence of OA fractions of liver and kidney extracts, substantial increase in APC was observed for tributylmethylammonium (TBuMA, Mw 200) and berberine (Mw 335), but not for triethylmethylammonium (TEMA, Mw 116) and tetraethylammonium (TEA, Mw 130). Because only QAs with higher Mw than a threshold (i.e., > 200) are known to form lipophilic ion-pair complexes with certain organic anions (e.g., bile salts such as taurodeoxycholate), above results are consistent with the hypothesis that only larger Mw QAs form lipophilic ion-pair complexes with endogenous organic anionic components of the liver and kidney extracts. Considering the comparable effect between the liver and kidney extracts on the APC of TBuMA regardless of far less (1/5) content of bile salts in the kidney extract, OAs other than bile salts in the kidney appear to contribute to the formation of lipophilic ion-pair complexes. Most interestingly, the secretory (i.e., basolateral to apical direction) transport of TBuMA and berberine across the LLC-PK1 cell monolayer was decreased by the cis-presence of the kidney extract, while remained unchanged for the transport of TEMA and TEA. The kidney extract had no effect on the absorptive (i.e., apical to basolateral direction) transport and cellular (LLC-PK1) accumulation of all of these QAs. Regardless of underlying mechanisms, it is notable that OA components of liver and kidney extracts influence the APC and secretory transport of QAs with Mw >200.


United States Neurosurgery Department Program Directors: A Cross-Sectional Evaluation of Current and Future Trends and Attributes.
While United States (U.S.) neurosurgery residency programs have been subject to many studies, none have focused solely on the program directors (PDs). We aim to analyze the demographic, educational, and academic attributes of this cohort to understand current and future trends of PDs. One hundred sixteen neurosurgeons listed as PDs at U.S. accredited neurosurgical residency training programs as of August 2022 were assessed. Descriptive data including age upon acceptance of role, gender, and h-index were collected from publicly available sources. Most PDs matriculated to their positions before the age of 45 years, were male, and had been hired internally. Approximately 25% of PDs had earned an additional degree. Departments with higher aggregate h-indexes were more likely to hire PDs with higher average publications per year (P < 0.001) and have a higher h-index (P < 0.001). PD subspecialty influenced h-index (P < 0.05) and total average publications per year (P < 0.05) with neuro-oncology subspecialists having higher averages in both. More recently hired PDs had a higher average number of publications per year (P < 0.05) and were more likely to hold an additional degree (odds ratio 1.14, P < 0.05). Female PDs were hired at a younger age (P < 0.05). Neurosurgery PDs typically rise to their position after 10 years of practice and more recent PD hires are more likely to have additional degrees and more publications. As academic neurosurgery becomes more competitive, increased academic productivity and acquisition of additional degrees will become increasingly necessary.


The Use of Antiepileptics in Migraine Prophylaxis.
Migraine is a chronic debilitating disorder. Selected antiepileptic drugs (AEDs) are proposed as preventives for migraine. Clinical efficacy and side effects of these AEDs are discussed. The American Academy of Neurology and the American Society of Headache classify topiramate (TPM) and divalproex sodium (DVPX) as Level-A medications and recommend offering them to patients for migraine prophylaxis. Their mechanism(s) of actions remains not entirely known. Their recognized action as sodium channel blockers may affect the neural component of migraine pain. TPM or DVPX can be considered an obvious choice for those patients with a concomitant seizure disorder. Care must be taken to plan their treatment with their psychiatrist if a mood disorder is present. DVPX tends not to be prescribed as first/second choice due to its potential for weight gain and hepatotoxicity. TPM is generally first choice, but bears severe contraindications. Both medications require education on teratogenesis in childbearing women. Consideration of gabapentin, acetazolamide, leviteracetam, zonisamide, and carbamazipine may be given later as empiric options and in selected patients. Patients must be made aware that there is insufficient scientific support for their use in migraine. Available AEDs to prophylactically treat migraine are few but of robust clinical efficacy. Special care needs to be exerted with respect to their side effects. Future research is needed for a better understanding of their mechanisms of action in migraine. Such research has the potential of providing some insight into the pathophysiology of migraine.


Truncation of PstS1 antigen of Mycobacterium tuberculosis improves diagnostic efficiency.
PstS1, also named 38-kDa antigen, is one of the earliest known immune-dominant antigens of Mycobacterium tuberculosis and it has been commonly used in serodiagnostic tests. We constructed a truncated version, tnPstS1, by removing 96 and 14 amino acid residues from the N- and C-terminals, respectively of the native PstS1. The native and the truncated 29.5 kDa proteins were expressed in insoluble forms in Escherichia coli to levels of 15% and 25% of the total cell proteins, respectively. Both the variant molecules reacted equally well with the antisera raised in rabbit against the native protein. PstS1 and tnPstS1 were evaluated through ELISA against plasma samples from 160 culture positive tuberculosis patients and 40 healthy controls. With tnPstS1 43% of the patient samples were detected positive for the antibody as compared to only 36% in the case of the native PstS1. Data for the secondary structures of the native and the truncated variants as obtained by circular dichroism agreed with the known 3-D structure of the native protein and the predicted structure of the truncated version, respectively. The results show that the truncated tnPstS1 is more efficient as compared to the native PstS1 for use as a serodiagnostic agent.


Enhanced production of xylanase by solid state fermentation using Trichoderma koeningi isolate: effect of pretreated agro-residues.
The main objective of this study was to isolate the fungal strain for enhanced production of xylanase using different agro-residues and fruit peels by solid state fermentation and its potentiality was tested on the pretreated corn cob. Fermentation was carried out with Trichoderma koeningi isolate using untreated and pretreated corn cob supplemented with pineapple peel powder showed higher production of xylanase 2,869.8 ± 0.4 (IU/g) and extracellular protein 7.6 ± 0.2 (mg/g) of corn cob, in the latter than the former yielding 1,347.2 ± 0.7 (IU/g) and 4.9 ± 0.1 (mg/g) of corn cob, respectively, at pH 6.5 and incubation period for 96 h. In the FT-IR spectrum, the bands at 1,155, 1,252 and 1,738 cm-1 had disappeared. This indicates the depolymerization of hemicellulose and the band at 1,053 cm-1 shows the presence of β (1-4)-xylan in the pretreated corn cobs. The pretreated biomass hydrolysed with a xylanase concentration of 14 U and 6 h incubation showed mainly xylose and its oligosaccharides, which were quantified using HPLC. From the results we can conclude that pretreated energy-value and cheaply available agro-residues can be effectively used as substrates for the enhanced production of xylanase.


Oral anticoagulation and clinical outcomes in COVID-19: An Italian multicenter experience.
Since the body of evidence addressing the coagulation derangements caused by Coronavirus disease (COVID-19) has been constantly growing, we investigated whether pre-hospitalization oral anticoagulation (OAC) or in-hospital heparin treatment could have a protective role among COVID-19 patients. In this cohort study, consecutive COVID-19 patients admitted to four different Italian Institutions were enrolled. Baseline demographic, clinical, laboratory, and radiological characteristics, as well as in-hospital treatment and outcomes were evaluated. The primary outcome was mortality. A total of 844 COVID-19 patients were enrolled as study cohort, n = 65 (7.7%) taking OACs prior to hospitalization. Regarding clinical outcomes, OAC patients developed acute hypoxemic respiratory failure (AHRF) more frequently than non-OAC patients as well as presenting a higher mortality rate (44.6% vs 19.8%, p < 0.001). At overall multivariate logistical regression, use of heparin (n = 394, 46.6%) was associated with a better chance of survival to hospital discharge (OR 0.60 [0.38-0.94], p < 0.001), in particular in patients with AHRF, with no association found with the use of OACs. In a sub-analysis, the highest mortality rate was found for AHRF patients when heparin was not administered. In our cohort, OACs appeared to be ineffective in reducing mortality rate, while heparin resulted to be a useful treatment when lung disease was sufficiently severe, potentially suggesting a crucial role of microthrombosis in severe COVID-19. Due to the relatively small number of COVID-19 patients treated with OACs included in our analysis and their higher number of comorbidities, larger studies are needed in order to confirm our findings.


Excitotoxic lesion of the hippocampus of Wistar rats disrupts the circadian control of the latent inhibition of taste aversion learning.
Previous experiments have shown that changes in the time of day between taste pre-exposure and conditioning prevent the latent inhibition of conditioning taste aversion. The effect of these changes in circadian context between pre-exposure and conditioning on the magnitude of the learned aversion appears to be similar to the effect of changes in spatial context on this type of learning. To elucidate the brain areas involved in this circadian dependence of latent inhibition of conditioning taste aversion, the effect of excitotoxic lesions of the hippocampus, a region related to spatial-contextual modulation in this learning process, was analyzed. The latent inhibition of conditioning taste aversion in animals with hippocampal lesions, that were pre-exposed and conditioned to the same or different time of day, was compared with the response of animals exposed to either conditions ("same" or "different") but had undergone amygdala lesions or sham lesions. The results showed that selective dorsal hippocampus lesion eliminated the circadian dependence of latent inhibition of taste aversion. A change in the time of day between pre-exposure and conditioning did not prevent latent inhibition in animals with hippocampal lesions. In contrast, this change prevented latent inhibition in the amygdala-lesioned and sham groups. These findings suggest that the hippocampus contains a selective mechanism that modulates the contextual dependency of the latent inhibition of conditioning taste aversion without interfering with the effect of taste pre-exposure itself. This study may help to understand the possible common involvement of the hippocampus in different types of contextual control of associative learning.


Natural killer cell activity in patients with pulmonary tuberculosis and in healthy controls.
Natural killer (NK) cell activity of freshly isolated peripheral blood mononuclear cells (MNC) or cells stimulated for 72 h with 10 micrograms/ml of a sonicate antigen of Mycobacterium tuberculosis H37Rv were studied in healthy responder and non-responder controls, as detected by lymphocyte proliferation with specific antigen, and in patients with pulmonary tuberculosis. K-652 cells were used as targets in a 4 h 51Cr release assay. MNC from patients exhibited a significant decrease in NK function as compared with responder controls (p less than 0.02). NK activity in responder individuals was highest 72 h after incubation with antigen. Non-stimulated cells were not cytotoxic. MNC from healthy responder and non-responder subjects incubated for 72 h with antigen yielded a significant increase in the percentage NK cytotoxicity at all effector/target ratios studied (p less than 0.01) as well as in the number of lytic units per culture (p less than 0.004). However, this increase was higher in responder individuals as compared to non-responder subjects (p = 0.02). The response to antigen was not significant in the group of patients although a net increase was also observed in the whole group. Only 4 of 9 patients exhibited significant increased responses after antigenic stimulation, 3 showed moderate responses, 1 did not respond and in a further patient a decrease was observed. The decreased NK activity could be secondary to abnormalities in the production of lymphokines by tuberculous patients. Although the role of non-specific cytotoxic cells in tuberculosis is unknown, their alterations could contribute to the pathogenesis of the disease.


Of the many cellular responses activated by TP53, which ones are critical for tumour suppression?
The tumour suppressor TP53 is a master regulator of several cellular processes that collectively suppress tumorigenesis. The TP53 gene is mutated in ~50% of human cancers and these defects usually confer poor responses to therapy. The TP53 protein functions as a homo-tetrameric transcription factor, directly regulating the expression of ~500 target genes, some of them involved in cell death, cell cycling, cell senescence, DNA repair and metabolism. Originally, it was thought that the induction of apoptotic cell death was the principal mechanism by which TP53 prevents the development of tumours. However, gene targeted mice lacking the critical effectors of TP53-induced apoptosis (PUMA and NOXA) do not spontaneously develop tumours. Indeed, even mice lacking the critical mediators for TP53-induced apoptosis, G1/S cell cycle arrest and cell senescence, namely PUMA, NOXA and p21, do not spontaneously develop tumours. This suggests that TP53 must activate additional cellular responses to mediate tumour suppression. In this review, we will discuss the processes by which TP53 regulates cell death, cell cycling/cell senescence, DNA damage repair and metabolic adaptation, and place this in context of current understanding of TP53-mediated tumour suppression.