Risk factors and management of urine leaks after partial nephrectomy.
As nephron sparing surgery is used more frequently for select renal tumors, the incidence of urine leaks will likely increase. To our knowledge the risk factors of and management strategies for urine leaks have not been studied. We report our experience with the risk factors of and management for urine leaks after open and laparoscopic partial nephrectomy. We retrospectively reviewed the records of 127 consecutive patients who underwent partial nephrectomy between 2001 and 2007, including 70 with open and 57 with laparoscopic partial nephrectomy, as performed by 3 surgeons. Urine leak was defined as drain output consistent with urine greater than 48 hours after laparoscopic partial nephrectomy. Of the patients 21 experienced a urine leak after partial nephrectomy, including 13.3% overall, and 10.5% after laparoscopic and 18.5% after open partial nephrectomy. Patients with a urine leak had significantly greater tumor size (3.2 vs 2.4 cm, p <0.044), endophytic locations (57% vs 19%, p <0.00027) and repair of collecting system defects during partial nephrectomy (95% vs 56%, p <0.00072). There was no association with the number of tumors removed, estimated blood loss, ischemia time, body mass index, age or other surgical complications. The median duration of urine leak was 20 days. While most urine leaks resolved with prolonged drainage, 38% of cases required further intervention. Patient age at surgery was the only factor that correlated with prolonged (greater than 30 days) urine leak. Urine leak is a complication unique to partial nephrectomy that is more commonly noted when a larger endophytic mass involves the renal collecting system. Most leaks resolve with prolonged drainage or replacement of a ureteral stent.


Limitations and drawbacks of 'fine bore' nasogastric feeding tubes.
The clinical use of unweighted nasogastric feeding tubes (n = 491) was compared with that of weighted nasogastric feeding tubes. No advantage was found in the use of the weighted tubes.


Transcriptomic heterogeneity of cultured ADSCs corresponds to embolic risk in the host.
Stem cell therapy emerges as an effective approach for treating various currently untreatable diseases. However, fatal and unknown risks caused by their systemic use remain to be a major obstacle to clinical application. We developed a functional single-cell RNA sequencing (scRNA-seq) procedure and identified that transcriptomic heterogeneity of adipose-derived stromal cells (ADSCs) in cultures is responsible for a fatal embolic risk of these cells in the host. The pro-embolic subpopulation of ADSCs in cultures was sorted by gene set enrichment analysis (GSEA) and verified by a supervised machine learning analysis. A mathematical model was developed and validated for the prediction of embolic risk of cultured ADSCs in animal models and further confirmed by its application to public data. Importantly, modification of culture conditions prevented the embolic risk. This novel procedure can be applied to other aspects of risk assessment and would help further the development of stem cell clinical applications.


Expression of metalloproteinase 2 in the cell response to porous demineralized bovine bone matrix.
The purpose of the study was to analyze the involvement of metalloproteinase 2 (MMP-2) and macrophages in the tissue and cell response to the organic graft material produced from bovine cancellous bone. Thirty adult male white Wistar rats (Rattus norvegicus) received implants of blocks of demineralized bovine bone matrix between the fasciae of the quadriceps muscle. The specimens collected at 3, 7, 14, 21 and 28 days after implantation (n = 6/period). Sections of 6 microm thick were stained with hematoxylin and eosin and immunolabeled with anti-MMP-2 and anti-CD68 using standard avidin-biotin-peroxidase method. The tissue response to the material was initially mediated by polymorphonuclear neutrophils, evolving to a mononuclear inflammatory infiltrate with macrophages and few lymphocytes and plasma cells and presence of inflammatory multinucleated giant cells (GC) in contact with the material that exhibited signs of resorption. The number of cells immunolabeled to MMP-2 was highest at day 7 (103.2 +/- 39.1), but significantly decreased (F = 3.67; p = 0.044) until day 28 (45.9 +/- 13.1). CD68 immunostaining also significantly decreased (F = 6.75; p = 0.007) from day 7 (49.5 +/- 10.4) to day 28 (19.5 +/- 8.9). A positive and statistically significant correlation was observed between the evolutions of these two variables. The material had been almost completely resorbed at day 28. Among cells present at the granuloma, anti-MMP-2 immunostaining was predominant and more intense in macrophages, yet lightly immunolabeled multinucleated giant cells were found in close contact with the material. Thus, considering the experimental limitations of this study, we concluded that MMP-2 produced by macrophages participates in the resorption of demineralized bovine bone.


Chronic myeloid leukaemia cells require the bone morphogenic protein pathway for cell cycle progression and self-renewal.
Leukaemic stem cell (LSC) persistence remains a major obstacle to curing chronic myeloid leukaemia (CML). The bone morphogenic protein (BMP) pathway is deregulated in CML, with altered expression and response to the BMP ligands shown to impact on LSC expansion and behaviour. In this study, we determined whether alterations in the BMP pathway gene signature had any predictive value for therapeutic response by profiling 60 CML samples at diagnosis from the UK SPIRIT2 trial and correlating the data to treatment response using the 18-month follow-up data. There was significant deregulation of several genes involved in the BMP pathway with ACV1C, INHBA, SMAD7, SNAIL1 and SMURF2 showing differential expression in relation to response. Therapeutic targeting of CML cells using BMP receptor inhibitors, in combination with tyrosine kinase inhibitor (TKI), indicate a synergistic mode of action. Furthermore, dual treatment resulted in altered cell cycle gene transcription and irreversible cell cycle arrest, along with increased apoptosis compared to single agents. Targeting CML CD34+ cells with BMP receptor inhibitors resulted in fewer cell divisions, reduced numbers of CD34+ cells and colony formation when compared to normal donor CD34+ cells, both in the presence and absence of BMP4. In an induced pluripotent stem cell (iPSC) model generated from CD34+ hematopoietic cells, we demonstrate altered cell cycle profiles and dynamics of ALK expression in CML-iPSCs in the presence and absence of BMP4 stimulation, when compared to normal iPSC. Moreover, dual targeting with TKI and BMP inhibitor prevented the self-renewal of CML-iPSC and increased meso-endodermal differentiation. These findings indicate that transformed stem cells may be more reliant on BMP signalling than normal stem cells. These changes offer a therapeutic window in CML, with intervention using BMP inhibitors in combination with TKI having the potential to target LSC self-renewal and improve long-term outcome for patients.


Phase I clinical trial of vaccination with LY6K-derived peptide in patients with advanced gastric cancer.
Lymphocyte antigen 6 complex locus K (LY6K) has been identified as a tumor-associated antigen in lung cancers and esophageal squamous cell carcinomas. The immunogenicity of LY6K-177 peptide vaccine therapy has been demonstrated in patients with advanced esophageal cancer. This study extends this treatment to gastric cancer. LY6K expression in clinical samples obtained from gastric cancer patients was examined by immunochemistry. As a phase I clinical trial, the safety and immunogenicity of LY6K-177 peptide vaccine emulsified with Montanide ISA 51 was evaluated in six patients with unresectable advanced gastric cancer. LY6K-177 peptide (1 mg in 1 ml sterile saline) was emulsified with incomplete Freund's adjuvant (1 ml) and intracutaneously administered to the inguinal region or axilla. One treatment course comprised four vaccinations, performed weekly for the first and second treatment courses and biweekly for the third treatment course. LY6K expression was confirmed in 85 % of gastric cancer tissues. Induration and redness at the vaccination site (grade I), possibly a delayed-type hypersensitivity reaction, was observed in all patients; however, no systemic toxicology was identified in any patient throughout the observation period. Three of the six patients had stable disease, and a tumor contraction effect was observed in one patient. LY6K was expressed in 85 % of observed gastric cancers. Vaccination with LY6K-177 peptide/Montanide ISA 51 appeared to be tolerated by advanced gastric cancer patients, and moreover anticancer efficacy was suggested. This trial was registered with ClinicalTrial.gov (no. NCT00845611).


iCare4Me for FTD: A pilot randomized study to improve self-care in caregivers of persons with frontotemporal degeneration.
A tremendous burden is placed on frontotemporal degeneration (FTD) caregivers who sacrifice their own self-care to manage the functional impairments of their loved one, contributing to high levels of stress and depression. Health coaching provides support for coping with stress while fostering self-care behaviors. We report on preliminary evidence for efficacy of a virtual health coach intervention aimed at increasing self-care. Thirty-one caregivers of persons with behavioral variant FTD (bvFTD) were assigned randomly to an intervention group, which included 10 coaching sessions over 6 months plus targeted health information or the control group receiving standard care augmented with the health information. Caregiver self-care (primary outcome), stress, depression, coping, and patient behavioral symptoms were collected at enrollment and 3 and 6 months. Change over time was evaluated between the intervention and control groups using linear mixed-effects models. There was a significant group-by-time interaction for self-care monitoring (t58 = 2.37, p = 0.02 and self-care confidence (t58 = 2.32, p = 0.02) on the Self-Care Inventory, demonstrating that caregivers who received the intervention improved their self-care over time. Behavioral symptoms were reduced in bvFTD patients whose caregivers received the intervention (t54 = -2.15, p = 0.03). This randomized controlled trial (RCT) shows promise for health coaching as a way to increase support that is urgently needed to reduce poor outcomes in FTD caregivers.


Biomimetic dual-nanozymes with catalytic cascade reactions against diabetic wound infection.
Diabetes-related chronic wounds characterized by hyperglycemia and weak alkaline milieu provide numerous advantages for bacteria growth and biofilm formation, setting a myriad of stumbling blocks for wound healing. Therefore, reshaping the spatially and temporally pathological wound microenvironment against bacterial infection is critical to rescue stalled healing progress in diabetes-related chronic wounds. Herein, we demonstrate on the room-temperature construction of a glucose oxidase (GOx)-mimicking and peroxidase (POD)-mimicking dual-nanozymes catalytic cascade system upon the partial reduction of Fe3+ to Fe2+ and the deposition of Au nanoparticles, simultaneously. The as-prepared dual-nanozymes catalytic cascade system possesses the capabilities of reshaping the pathological microenvironments of diabetic wound via glucose consumption and acidification, leading to amplified catalytic cascade activities for sterilization. On the one hand, the GOx-mimicking enzymatic activity of the catalytic cascade system can not only deplete glucose and acidize wound milieu to inhibit bacteria growth, but also utilize the weak alkaline milieu of diabetic wound to provide sufficient H2O2 and a favorable pH for subsequent OH generation. On the other hand, the POD-mimicking enzymatic activity of the catalytic cascade system can continuously produce OH for sterilization under the weak acidic milieu in the presence of abundant H2O2. Benefiting from the simply and mild preparation process and the excellent dual-nanozymes catalytic cascade activities under the deliberate evolved milieus of diabetes-related chronic wounds, our catalytic cascade system exhibits the promising healing effect and clinical translation potential against diabetic wound infection.


Novel iron-chelating peptide from egg yolk: Preparation, characterization, and iron transportation.
In this work, an egg yolk protein hydrolysate (EYPH) with a high iron-chelating ability (87.32%) was prepared. The fractionation using 60% (v/v) ethanol concentration (E3 fraction) led to the efficiently accumulating the iron-chelating peptides in EYPH. The characterization results showed that iron mainly chelated with carboxyl, amino and phosphate groups of peptides. From E3 fraction, six iron-chelating peptides with MW ranging from 1372.36 to 2937.04 Da were identified and a hypothesized molecular model of DDSSSpSpSpSpSpSVLSK-Fe was simulated. In vitro stability determination showed that E3-Fe chelate owned a good heat, alkalinity and digestion tolerance, but a relatively bad acid tolerance. Finally, iron transport analysis showed that iron in the E3-Fe would be absorbed in caco-2 cell membrane more effectively than that of iron salts, indicating that it was possible to apply the E3-Fe complex as iron supplements.


Epidural anaesthesia and postoperative colorectal motility--a possible hazard to a colorectal anastomosis.
The effects of epidural anaesthesia (EDA, mepivacaine) and EDA in combination with atropine and neostigmine on postoperative intestinal motility were studied in 17 patients undergoing operation for cancer of the rectum or sigmoid colon. Motility was recorded by a volumetric technique. Epidural anaesthesia (EDA) increased motor activity in the small bowel as well as in the left colon and rectum. Phasic motility dominated in the small intestine whereas tonic and segmental contractions were recorded from the large bowel. EDA induced a powerful tonic contraction with a concomitant shortening of the rectum. This effect was inhibited by atropine. The influence of atropine/neostigmine on left colonic motor activity was studied in six patients before and during EDA in a cross-over fashion. When administered alone, atropine/neostigmine did not cause any motility increase. Atropine/neostigmine administered during EDA, however, elicited a significant increase of motility. The increase of intestinal motor activity induced by EDA may expose a newly constructed colorectal anastomosis to undue strain in the immediate postoperative period. When EDA is used in combination with general anaesthesia, particular attention should be directed towards the use of neostigmine for reversing the effect of nondepolarizing muscle relaxants. Atropine appears under such circumstances not to protect from the excitatory effects of this drug on colorectal motility.


Cardiovascular disease mortality and serum carotenoid levels: a Japanese population-based follow-up study.
Some observational epidemiologic studies suggest that dietary and serum carotenoids are associated with reduced cardiovascular disease mortality. Three thousand and sixty-one subjects (1,190 males and 1,871 females), aged 39 to 80 years, were recruited from residents of Hokkaido, Japan who had attended comprehensive health check-up programs from 1988 through 1995. Serum levels of alpha-carotene, beta-carotene, and lycopene were separately determined by high-performance liquid chromatography. Serum levels of total carotene consisted of the sum of alpha-carotene, beta-carotene, and lycopene levels. Each serum level of alpha-carotene, beta-carotene, lycopene, total carotene, triglyceride, and alanine transaminase (ALT) activity was transformed logarithmically. The hazard ratios of serum alpha- and beta-carotenes, lycopene, and total carotene values were estimated by the Cox proportional hazard model after adjusting for sex, age, and other potential confounding factors. During the 11.9-year follow-up period, 80 deaths (49 males and 31 females) from cardiovascular disease, 40 deaths from heart disease, and 37 deaths from stroke were identified among the cohort subjects. High serum values of carotenoids such as alpha- and beta-carotenes, and lycopene were found to be significantly associated with low hazard ratios for cardiovascular disease mortality. However, a significant inverse association between high serum lycopene value and the risk for stroke mortality was not always observed. High serum levels of total carotene, comprising alpha- and beta-carotenes and lycopene, may reduce the risk for cardiovascular disease mortality among the Japanese population.


Strength Analyses of Screws for Femoral Neck Fractures.
This article represents a multidisciplinary approach to biomechanics (engineering + medicine) in the field of "collum femoris" fractures. One possible treatment method for femoral neck fractures, especially for young people, is the application of cancellous (i.e. lag or femoral) screws (with full or cannulated cross-section) made of Ti6Al4V or stainless steel. This paper therefore aims to offer our own numerical model of cancellous screws together with an assessment of them. The new, simple numerical model presented here is derived together with inputs and boundary conditions and is characterized by rapid solution. The model is based on the theory of beams on an elastic foundation and on 2nd order theory (set of three differential 4th order equations, combination of pressure and bending stress-deformation states). It presents the process for calculating displacements, slopes, bending moments, stresses etc. Two examples (i.e. combinations of cancellous screws with full or cannulated cross-section made of stainless steel or Ti6Al4V material) are presented and evaluated (i.e. their displacement, slopes, bending moments, normal forces, shearing forces and stresses). Future developments and other applications are also proposed and mentioned.


Dose-volume thresholds and smoking status for the risk of treatment-related pneumonitis in inoperable non-small cell lung cancer treated with definitive radiotherapy.
To identify clinical risk factors and dose-volume thresholds for treatment-related pneumonitis (TRP) in patients with non-small cell lung cancer (NSCLC). Data were retrospectively collected from patients with inoperable NSCLC treated with radiotherapy with or without chemotherapy. TRP was graded according to Common Terminology Criteria for Adverse Events, version 3.0, with time to grade > or = 3 TRP calculated from start of radiotherapy. Clinical factors and dose-volume parameters were analyzed for their association with risk of TRP. Data from 576 patients (75% with stage III NSCLC) were included in this study. The Kaplan-Meier estimate of the incidence of grade > or = 3 TRP at 12 months was 22%. An analysis of dose-volume parameters identified a threshold dose-volume histogram (DVH) curve defined by V(20) < or = 25%, V(25) < or = 20%, V(35) < or = 15%, and V(50) < or = 10%. Patients with lung DVHs satisfying these constraints had only 2% incidence of grade > or = 3 TRP. Smoking status was the only clinical factor that affected the risk of TRP independent of dosimetric factors. The risk of TRP varied significantly, depending on radiation dose-volume parameters and patient smoking status. Further studies are needed to identify biological basis of smoking effect and methods to reduce the incidence of TRP.


Flavonoids against non-physiologic inflammation attributed to cancer initiation, development, and progression-3PM pathways.
Inflammation is an essential pillar of the immune defense. On the other hand, chronic inflammation is considered a hallmark of cancer initiation and progression. Chronic inflammation demonstrates a potential to induce complex changes at molecular, cellular, and organ levels including but not restricted to the stagnation and impairment of healing processes, uncontrolled production of aggressive ROS/RNS, triggered DNA mutations and damage, compromised efficacy of the DNA repair machinery, significantly upregulated cytokine/chemokine release and associated patho-physiologic protein synthesis, activated signaling pathways involved in carcinogenesis and tumor progression, abnormal tissue remodeling, and created pre-metastatic niches, among others. The anti-inflammatory activities of flavonoids demonstrate clinically relevant potential as preventive and therapeutic agents to improve individual outcomes in diseases linked to the low-grade systemic and chronic inflammation, including cancers. To this end, flavonoids are potent modulators of pro-inflammatory gene expression being, therefore, of great interest as agents selectively suppressing molecular targets within pro-inflammatory pathways. This paper provides in-depth analysis of anti-inflammatory properties of flavonoids, highlights corresponding mechanisms and targeted molecular pathways, and proposes potential treatment models for multi-level cancer prevention in the framework of predictive, preventive, and personalized medicine (PPPM / 3PM). To this end, individualized profiling and patient stratification are essential for implementing targeted anti-inflammatory approaches. Most prominent examples are presented for the proposed application of flavonoid-conducted anti-inflammatory treatments in overall cancer management. The online version contains supplementary material available at 10.1007/s13167-021-00257-y.


Bone alkaline phosphatase: An important biomarker in chronic kidney disease - mineral and bone disorder.
Increased cardiovascular morbidity and mortality in chronic kidney disease (CKD) represents an emerging major health problem. Indeed, disturbances in mineral and bone metabolism occur frequently in CKD and are termed chronic kidney disease - mineral and bone disorder (CKD-MBD). These can lead to cardiovascular pathology, resulting in an increased cardiovascular risk. Bone alkaline phosphatase (BALP) is essential for biomineralization. Recent findings demonstrate a crucial role for BALP in the pathogenesis of vascular calcification and identified it as a promising predictor of mortality in CKD. In conjunction with parathyroid hormone (PTH), serum BALP has been suggested as a biomarker of bone turnover in CKD-MBD. In contrast to PTH, serum BALP demonstrates a lower variability and may thus be better suited for the diagnosis and longitudinal follow-up of bone turnover. The linear association with mortality, compared to the U-shaped curve for PTH, is an additional advantage, making BALP more suitable than PTH as a treatment target in CKD. Here we review the main characteristics of alkaline phosphatase isozymes/isoforms and the various assays currently used in clinical routine laboratories. We also discuss the role of BALP in both physiological and pathological mineralization, and the clinical benefit of BALP determination in CKD.


Hypoxic up-regulation of triosephosphate isomerase expression in mouse brain capillary endothelial cells.
A protein with a molecular mass of 27kDa was induced by hypoxia in a mouse brain capillary endothelial cell line and identified as triosephosphate isomerase (TPI) by amino-terminal sequencing. Hypoxia caused an elevation of the TPI protein level, concomitant with an increase of the TPI mRNA level. However, hypoxia resulted in an insufficient elevation of TPI activity level, compared to an increase of TPI protein level. When cells expressing the recombinant TPI protein with histidine tag were exposed to hypoxia and the TPI protein was affinity-purified, the catalytic activity (specific activity) of the TPI protein purified from hypoxic cells was substantially lower than that obtained from normoxic cells. In addition, three TPI isoforms with an electrophoretic multiplicity were found; two of the three isoforms were substantially increased in response to the hypoxia, but the level of the most acidic isoform was barely changed. The induction of TPI gene expression by hypoxia was suppressed by (1) a chelator of intracellular Ca(2+), (2) a blocker of non-selective cation channels, (3) a blocker of Na(+)/Ca(2+) exchangers, (4) an inhibitor of Ca(2+)/calmodulin-dependent protein kinases, and (5) an inhibitor of c-jun/AP-1 activation.


Efficacy of laparoscopy-assisted distal gastrectomy for gastric cancer in the elderly.
To date, it has been unclear whether laparoscopy-assisted distal gastrectomy (LADG) is a suitable treatment for elderly patients with early gastric cancer. This study retrospectively compared surgical outcomes between elderly and nonelderly patients with gastric cancer. The study group was comprised of 211 patients who underwent distal gastrectomy between April 2000 and March 2007. Of these, 130 patients (26 aged >or=75 years and 104 aged <75 years) underwent LADG, and the remaining 81 patients underwent conventional open distal gastrectomy (ODG). Short- and long-term patient outcomes were evaluated. The operation time was significantly longer in the LADG group than in the ODG group (262.6 versus 234.3 min, p = 0.005), but the other short-term outcomes did not differ between the two groups. When performed by an experienced surgeon, blood loss was significantly reduced, while operation time for LADG was similar to that for ODG. Within the LADG group, incidences of comorbid disease and lymph-node metastasis were significantly greater, the histological tumor type was significantly more differentiated, and the macroscopically depressed tumor type was less common in elderly patients. However, the incidence of postoperative morbidity did not differ between the elderly and nonelderly groups (11.5% versus 3.8%, p = 0.1201), and there was no significant difference in postoperative course. Logistic regression analysis showed that body mass index, but not chronological age, was an independent predictive factor of postoperative morbidity (odds ratio = 3.674, p = 0.045). There were no significant differences in overall or disease-specific survival between elderly and nonelderly patients. LADG is an effective treatment for elderly patients with early gastric cancer if it is performed by an experienced surgeon. A high-volume study is needed to confirm this rationale.


Prolonged immunoglobulin and platelet infusion for treatment of immune thrombocytopenia.
Immune thrombocytopenia (ITP) may be associated with serious hemorrhage. We describe 2 patients who received intravenous immunoglobulin given as a 24-hr continuous infusion with a concomitant continuous infusion of platelets. This regimen was rapidly effective in increasing platelet counts in both patients.


The possible mutagenic effect of the occupation of TV announcer.
In a group of TV announcers, a significant increase in the number of classical aberrations was detected in peripheral blood: 7.5 +/- 3.477% in comparison with 3 control groups (A - 7 healthy women matched for sex, age and place of residence, B - 9 members of TV technical staff, C - 9 actors and actresses) with a mean aberration level of 2.96 +/- 1.136. SCE numbers were not increased in the TV announcers compared to controls. An increased frequency of reproduction failure has also been noticed in TV announcers (females). A decrease in the level of aberrant cells was noticed when the announcer had been on holiday, although this was not statistically significant. The possible mutagens in the working environment of TV announcers are discussed; there is a suspicion that azodyes, present in cosmetics or other chemicals, may be the mutagenic factor.


The response of metal mobilization and redistribution to reoxygenation in Baltic Sea anoxic sediments.
To bring life back to anoxic coastal and sea basins, reoxygenation of anoxic/hypoxic zones has been proposed. This research focuses on the metals released during the oxidization of sediments from two locations in the anoxic Eastern Gotland Basin under a laboratory-scale study. Triplicate experimental cores and reference cores were collected from the North and South Eastern Gotland Basins. The oxygenation of the water column took place over a 96-hour experiment in a dark and 5 °C environment. In 12 and 24 hour intervals, the surface waters were exchanged and, over time, analyzed for pH, electroconductivity (EC), total organic carbon (TOC), soluble metal concentrations, and the top samples (0-10 cm) were analyzed with 3-step (E1: water-soluble, E2: exchangeable, and E3: organic-bound) sequential chemical extraction (SCE). Results show stable pH and decreasing EC in the column waters. The EC indicates that metals are released in the initial phases (12 h) of reoxygenation for both sites. Arsenic, Ba, Co, Mn, Rb, U, K, Sr, and Mo are released into the water column during the 96 hour experiment, and based on the calculations for the entire East Gotland Basin, would mean 8, 50, 0.55, 734, 53, 27, 347,178, 3468, and 156 μg L-1 are released, respectively. Elements Mn, Mo, U, and As are released in higher concentrations during the experiment than previously measured in the Eastern Gotland Basin, which provides vital information for future proposed remediation and natural geochemical processes with their known environmental impacts. The SCE results show that redox-sensitive metals (Mn, U, and Mo) are released in the highest concentrations into the solution. The relationship between the highest released metals (beside redox-sensitive) into solution over the oxygenation and their initial abundant phase is noticed, where the smallest released concentrations belong to K < Rb < Sr in E2, and As<Ba in E3, respectively.


The effects of diethylcarbamazine on the ultrastructure of microfilariae of Wuchereria bancrofti in vivo and in vitro.
An ultrastructural study of microfilariae of Wuchereria bancrofti was performed after treatment in vitro and in vivo with diethylcarbamazine citrate (DEC). The morphological alterations produced by treatment in vitro with 5 micro g/ml of DEC were the loss of microfilarial sheaths and lysis of the cytoplasm, with the destruction of all organelles and the formation of several vacuoles, the contents of which presented various degrees of electron-density, or showed an empty appearance. Some of these vacuoles seemed to be extruding from the cytoplasm as apoptotic bodies and others presented organelles inside. Similar alterations were observed after in vivo treatment. At 40 min after treatment of a microfilaremic individual with DEC, almost all microfilariae observed had lost their sheaths; and, in some of them, remains of the microfilarial sheath on the larval surface could be detected. Numerous vacuoles were observed, mainly in the hypodermis and somatic cells, showing organelles inside or an empty appearance. Condensed chromatin was also observed in some somatic cells. At 1 h after treatment of a microfilemic individual with DEC, microfilariae presented drastic morphological alterations, with large vacuoles within somatic cell cytoplasm and complete lysis of all cellular organelles. Therefore, both treatments with DEC in vitro and in vivo had a direct mechanism of action on the microfilariae of W. bancrofti, including organelle damage and apoptosis.


Demethyleneberberine, a potential therapeutic agent in neurodegenerative disorders: a proposed mechanistic insight.
Neurodegenerative disorders are a diverse variety of diseases that can be distinguished from developing degeneration of neurons in the CNS. Several alkaloids have shown mounting effects in neurodegenerative disorders, and berberine is one of them. Demethyleneberberine is a metabolite of berberine that has better blood-brain barrier crossing capacity. Demethyleneberberine possesses anti-inflammatory, anti-oxidant, and mitochondrial targeting properties. However, neither the pharmacological action nor the molecular mechanism of action of demethyleneberberine on neurodegenerative disorders has been explored yet. A systematic literature review of PubMed, Medline, Bentham, Scopus, and EMBASE (Elseveier) databases was carried out with the help of keywords like "Demethyleneberberine; neuroinflammation; oxidative stress; Neuroprotective; Neurodegenerative disorders" till date. This review focus on the neuroprotective potential of demethyleneberberine in neurodegenerative disorders by attenuating different pathways, i.e., NF-κB, MAPK, and AMPK signalling.


Potentiated glucose deprivation-induced death of astrocytes after induction of iNOS.
Astrocytes play an essential role in the maintenance of normal neuronal function. Here we report that pretreatment of interferon-gamma (IFN-gamma) and lipopolysaccharides (LPS) made murine astrocytes highly vulnerable to glucose deprivation-induced death. Neither 12-hr glucose deprivation nor 2-day treatment with IFN-gamma (100 U/ml) and LPS (1 microg/ml) altered the viability of astrocytes. However, significant death of IFN-gamma/LPS-treated astrocytes was observed after 4-hr glucose deprivation. This augmented death was mimicked by the nitric oxide releasing reagent 3-morpholinosydnonimine and was in part prevented by the nitric oxide synthase inhibitor NG-nitroarginine. The data indicate that immunostimulated astrocytes can undergo suicidal death during glucose deprivation through the expression of inducible nitric oxide synthase.


Cerebral oxygenation and hemodynamics during hyperventilation and sleep in patients with Rett syndrome.
We continuously monitored changes in cerebral oxygenation and hemodynamics in the frontal lobes of six patients with Rett syndrome during the awake state, which is associated with hyperventilation (HV) and breath-holding (BH), and during sleep by near-infrared spectroscopy. We also monitored three adult volunteers during simulated episodes of HV and BH. In patients with Rett syndrome, the oxygenated hemoglobin (HbO2) and total hemoglobin (HbT) decreased significantly during HV and BH in the awake state compared with the sleep state. The HbO2 and HbT decreased gradually in adult volunteers in response to prolonged episodes of HV and BH. Further studies are required to investigate the relationship, if any, between the discovered continuous decreases in HbO2 and HbT during the awake state and the brain damage seen in patients with Rett syndrome.


Measurement of lipid peroxidation in vivo: a comparison of different procedures.
A study was undertaken to investigate whether some of the methods commonly used to detect lipid peroxidation of cellular membranes in vivo correlate with each other. The study was performed with the livers of bromobenzene-intoxicated mice, in which lipid peroxidation develops when the depletion of glutathione (GSH) reaches a threshold value. The methods tested and compared were the following: i) measurement of the malondialdehyde (MDA) content of the liver; ii) detection of diene conjugation absorption in liver phospholipids; iii) measurement of the loss of polyunsaturated fatty acids in liver phospholipids; and iv) determination of carbonyl functions formed in acyl residues of membrane phospholipids as a result of the peroxidative breakdown of phospholipid fatty acids. Correlations among the values obtained with these methods showed high statistical significances, indicating that the procedures measure lipid peroxidation in vivo with comparable reliability. Analogously, the four methods appeared also to correlate when applied to in vitro microsomal lipid peroxidation.


Variation in advanced stage at diagnosis of lung and female breast cancer in an English region 2006-2009.
Understanding variation in stage at diagnosis can inform interventions to improve the timeliness of diagnosis for patients with different cancers and characteristics. We analysed population-based data on 17,836 and 13,286 East of England residents diagnosed with (female) breast and lung cancer during 2006-2009, with stage information on 16,460 (92%) and 10,435 (79%) patients, respectively. Odds ratios (ORs) of advanced stage at diagnosis adjusted for patient and tumour characteristics were derived using logistic regression. We present adjusted ORs of diagnosis in stages III/IV compared with diagnosis in stages I/II. For breast cancer, the frequency of advanced stage at diagnosis increased stepwise among old women (ORs: 1.21, 1.46, 1.68 and 1.78 for women aged 70-74, 75-79, 80-84 and ≥85, respectively, compared with those aged 65-69 , P<0.001). In contrast, for lung cancer advanced stage at diagnosis was less frequent in old patients (ORs: 0.82, 0.74, 0.73 and 0.66, P<0.001). Advanced stage at diagnosis was more frequent in more deprived women with breast cancer (OR: 1.23 for most compared with least deprived, P=0.002), and in men with lung cancer (OR: 1.14, P=0.011). The observed patterns were robust to sensitivity analyses approaches for handling missing stage data under different assumptions. Interventions to help improve the timeliness of diagnosis of different cancers should be targeted at specific age groups.


Purity, adulteration and price of drugs bought on-line versus off-line in the Netherlands.
On-line drug markets flourish and consumers have high expectations of on-line quality and drug value. The aim of this study was to (i) describe on-line drug purchases and (ii) compare on-line with off-line purchased drugs regarding purity, adulteration and price. Comparison of laboratory analyses of 32 663 drug consumer samples (stimulants and hallucinogens) purchased between January 2013 and January 2016, 928 of which were bought on-line. The Netherlands. Primary outcome measures were (i) the percentage of samples purchased on-line and (ii) the chemical purity of powders (or dosage per tablet); adulteration; and the price per gram, blotter or tablet of drugs bought on-line compared with drugs bought off-line. The proportion of drug samples purchased on-line increased from 1.4% in 2013 to 4.1% in 2015. The frequency varied widely, from a maximum of 6% for controlled, traditional substances [ecstasy tablets, 3,4-methylenedioxy-methamphetamine (MDMA) powder, amphetamine powder, cocaine powder, 4-bromo-2,5-dimethoxyphenethylamine (2C-B) and lysergic acid diethylamide (LSD)] to more than a third for new psychoactive substances (NPS) [4-fluoroamphetamine (4-FA), 5/6-(2-aminopropyl)benzofuran (5/6-APB) and methoxetamine (MXE)]. There were no large differences in drug purity, yet small but statistically significant differences were found for 4-FA (on-line 59% versus off-line 52% purity for 4-FA on average, P = 0.001), MDMA powders (45 versus 61% purity for MDMA, P = 0.02), 2C-B tablets (21 versus 10 mg 2C-B/tablet dosage, P = 0.49) and ecstasy tablets (131 versus 121 mg MDMA/tablet dosage, P = 0.05). The proportion of adulterated samples purchased on-line and off-line did not differ, except for 4-FA powder, being less adulterated on-line (χ2 = 8.3; P < 0.02). Drug prices were mainly higher on-line, ranging for various drugs from 10 to 23% higher than that of drugs purchased off-line (six of 10 substances: P < 0.05). Dutch drug users increasingly purchase drugs on-line: new psychoactive substances in particular. Purity and adulteration do not vary considerably between drugs purchased on-line and off-line for most substances, while on-line prices are mostly higher than off-line prices.


The application of 3D-printed titanium mesh in maxillary tumor patients undergoing total maxillectomy.
To evaluate the clinical outcomes of reconstruction of maxillary class III defect using 3D-printed titanium mesh. Twelve patients with maxillary class III defect from April 2015 to December 2016 were retrospectively studied. A 3D individualized maxillary stereo model based on mirror images of the unaffected maxilla was obtained to fabricate an anatomically adapted titanium mesh using computer-assisted design and manufacture. The individual titanium mesh was inserted into the maxillary class III defect after total maxillectomy. The incidence of postoperative complications was evaluated. The postoperative orbital volume and protrusion degree of eye were measured. All patients were satisfied with their postoperative facial symmetry, without developing diplopia or endophthalmos. The postoperative orbital volumes were 26.41 ± 0.52 mL on the affected side and 26.55 ± 0.45 mL on the unaffected side. The postoperative protrusion degrees of affected and unaffected eyes were 16.21 ± 0.48 and 16.82 ± 0.79 mm, respectively. Titanium mesh exposure was observed in 2 patients and mild limitation of mouth opening was observed in 4 patients who underwent postoperative radiotherapy. Reconstruction of maxillary class III defect with 3D-printed titanium mesh can achieve successful clinical outcomes, which recovered orbital volume and protrusion degree of eye. Twelve patients with maxillary class III defect were satisfied with their postoperative facial symmetry, without developing diplopia or endophthalmos. We investigated that reconstruction of maxillary class III defect with 3D-printed titanium mesh can achieve successful clinical outcomes.


Anterior Pituitary Volume in Patients with Transfusion Dependent Anemias: Volumetric Approaches and Relation to Pituitary MRI‑R2.
Anterior pituitary iron overload and volume shrinkage is common in patients with transfusion-dependent anemia and associated with growth retardation and hypogonadotropic hypogonadism. We investigated the accuracy of different MRI-based pituitary volumetric approaches and the relationship between pituitary volume and MRI-R2, particularly with respect to growth and hypogonadism. In 43 patients with transfusion-dependent anemia (12-38 years) and 32 healthy controls (12-72 years), anterior pituitary volume was measured by a sagittal T1 GRE 3D sequence at 1.5T and analyzed by 3D semi-automated threshold volumetry (3D-volumetry). This reference method was compared with planimetric 2D-volumetry, approximate volume calculations, and pituitary height. Using a multiple SE sequence, pituitary iron as MRI-R2 was assessed by fitting proton signal intensities to echo times. Growth and hypogonadism were obtained from height percentile tables and patients' medical charts. From body surface area and age adjusted anterior pituitary volumes of controls, Z‑scores were calculated for all subjects. Separation of controls and patients with respect to Z and pituitary R2 was performed by bivariate linear discriminant analysis. Tuned 2D volumes showed highest agreement with reference 3D-volumes (bias -4.8%; 95% CI:-8.8%|-0.7%). A linear discriminant equation of Z = -17.8 + 1.45 · R2 revealed optimum threshold sensitivity and specificity of 65% and 100% for discrimination of patients from controls, respectively. Of correctly classified patients 71% and 75% showed hypogonadism and growth retardation, respectively. Accurate assessment of anterior pituitary size requires 3D or precise 2D volumetry, with shorter analysis time for the latter. Anterior pituitary volume Z‑scores and R2 allow for the identification of patients at risk of pituitary dysfunction.


The effects of nurse staffing on hospital financial performance: competitive versus less competitive markets.
Hospitals facing financial uncertainty have sought to reduce nurse staffing as a way to increase profitability. However, nurse staffing has been found to be important in terms of quality of patient care and nursing-related outcomes. Nurse staffing can provide a competitive advantage to hospitals and as a result of better financial performance, particularly in more competitive markets. In this study, we build on the Resource-Based View of the Firm to determine the effect of nurse staffing on total profit margin in more competitive and less competitive hospital markets in Florida. By combining a Florida statewide nursing survey with the American Hospital Association Annual Survey and the Area Resource File, three separate multivariate linear regression models were conducted to determine the effect of nurse staffing on financial performance while accounting for market competitiveness. The analysis was limited to acute care hospitals. Nurse staffing levels had a positive association with financial performance (β = 3.3, p = .02) in competitive hospital markets, but no significant association was found in less competitive hospital markets. Hospitals in more competitive hospital markets should reconsider reducing nursing staff, as these cost-cutting measures may be inefficient and negatively affect financial performance.


Implicit Riesz wavelets based-method for solving singular fractional integro-differential equations with applications to hematopoietic stem cell modeling.
Riesz wavelets in L 2 ( R ) have been proven as a useful tool in the context of both pure and numerical analysis in many applications, due to their well prevailing and recognized theory and its natural properties such as sparsity and stability which lead to a well-conditioned scheme. In this paper, an effective and accurate technique based on Riesz wavelets is presented for solving weakly singular type of fractional order integro-differential equations with applications to solve system of fractional order model that describe the dynamics of uninfected, infected and free virus carried out by cytotoxic T lymphocytes (CTL). The Riesz wavelet in this work is constructed via the smoothed pseudo-splines refinable functions. The advantage of using such wavelets, in the context of fractional and integro-differential equations, lies on the simple structure of the reduced systems and in the powerfulness of obtaining approximated solutions for such equations that have weakly singular kernels. The proposed method shows a good performance and high accuracy orders.


Dietary curcumin nanoparticles promoted the performance, antioxidant activity, and humoral immunity, and modulated the hepatic and intestinal histology of Nile tilapia fingerlings.
The current study investigated the effects of dietary curcumin nanoparticles (C-NPs) on the performance, hemato-biochemical profile, digestive enzymes activities, antioxidant status, humoral immunity, and liver and intestinal histology of Nile tilapia (Oreochromis niloticus). Fish (4.3 ± 0.5 g) were fed with diets enriched with 0.0 (control), 15, 30, 45, and 60 mg C-NPs/kg diet up to apparent satiety thrice a day for 60 days. The growth-stimulating effects of dietary C-NPs were significantly observed in terms of final weight, weight gain %, specific growth rate, and feed intake. Compared with the control group, serum amylase, lipase, and proteases activities of Nile tilapia significantly (P < 0.05) increased alongside the increase in dietary levels of C-NPs in a dose-dependent manner. The counts of red blood cells and white blood cells as well as hemoglobin and hematocrit levels of Nile tilapia fed with 30-60 mg C-NPs/kg diet were statistically (P < 0.05) higher than fish in the control group with no significant differences among them (P > 0.05). Moreover, lymphocytes and monocytes significantly (P > 0.05) increased; meanwhile neutrophils significantly (P > 0.05) decreased as C-NPs levels in diets increased. In a similar trend, antioxidant (malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase) and humoral immunity (lysozyme and total immunoglobulin) biomarkers were significantly higher in C-NPs-fed fish. Liver histology showed improvements in the cell architecture of fish fed with C-NPs containing diets up to 45 mg/kg diet. Compared with the control diet, feeding Nile tilapia with C-NPs diets resulted in a higher villi length/width and absorption area. According to the regression curves, the current study recommends using the dietary C-NP with optimum values of 45-55 mg/kg diet to improve the performance, digestive enzymes, antioxidant activities, and immunity response of Nile tilapia.


[Correct use of prostate-specific antigen in office practice].
To standardize interpretation and comments of prostate-specific antigen (PSA) assay results by clinical pathology laboratories in office practice. From September 2004 to May 2006, interpretation and comments of PSA assay results performed by 100 different laboratories were analysed retrospectively. Nineteen different PSA assay kits were used. The so-called "normal" value for total PSA was less than 4 ng/ml for two-thirds of kits. Determination of the free PSA/total PSA ratio (91 cases) was based on a cut-off value ranging from 10 to 25% and the frequent laboratory comments (89 cases) more often referred to benign prostatic hyperplasia (51 case) than prostate cancer (nine cases). The marked diversity of PSA assay techniques currently used and the divergent interpretations by various laboratories lead to problems of interpretation for both practitioners and patients.


Innate and adaptive immunity: the yin and yang of celiac disease.
Celiac disease is a multigenetic complex inflammatory disorder with an autoimmune component, induced by gluten, a protein found in wheat. It is a unique human disease model to dissect the innate and adaptive immune mechanisms underlying T-cell-mediated tissue destruction and the development of T-cell lymphoma in conditions of chronic T-cell activation.


Bilateral transfer of motor performance as a function of motor imagery training: a systematic review and meta-analysis.
The objective of this review was to evaluate the efficacy of mental imagery training (MIT) in promoting bilateral transfer (BT) of motor performance for healthy subjects. We searched 6 online-databases (Jul-Dec 2022) using terms: "mental practice," "motor imagery training," "motor imagery practice," "mental training," "movement imagery," "cognitive training," "bilateral transfer," "interlimb transfer," "cross education," "motor learning," "strength," "force" and "motor performance." We selected randomized-controlled studies that examined the effect of MIT on BT. Two reviewers independently determined if each study met the inclusion criteria for the review. Disagreements were resolved through discussion and, if necessary, by a third reviewer. A total of 9 articles out of 728 initially identified studies were chosen for the meta-analysis. The meta-analysis included 14 studies for the comparison between MIT and no-exercise control (CTR) and 15 studies for the comparison between MIT and physical training (PT). MIT showed significant benefit in inducing BT compared to CTR (ES = 0.78, 95% CI = 0.57-0.98). The effect of MIT on BT was similar to that of PT (ES = -0.02, 95% CI = -0.15-0.17). Subgroup analyses showed that internal MIT (IMIT) was more effective (ES = 2.17, 95% CI = 1.57-2.76) than external MIT (EMIT) (ES = 0.95, 95% CI = 0.74-1.17), and mixed-task (ES = 1.68, 95% CI = 1.26-2.11) was more effective than mirror-task (ES = 0.46, 95% CI = 0.14-0.78) and normal-task (ES = 0.56, 95% CI = 0.23-0.90). No significant difference was found between transfer from dominant limb (DL) to non-dominant limb (NDL) (ES = 0.67, 95% CI = 0.37-0.97) and NDL to DL (ES = 0.87, 95% CI = 0.59-1.15). This review concludes that MIT can serve as a valuable alternative or supplement to PT in facilitating BT effects. Notably, IMIT is preferable to EMIT, and interventions incorporating tasks that have access to both intrinsic and extrinsic coordinates (mixed-task) are preferred over those that involve only one of the two coordinates (mirror-task or normal-task). These findings have implications for rehabilitation of patients such as stroke survivors.


How appropriate are the English language test requirements for non-UK-trained nurses? A qualitative study of spoken communication in UK hospitals.
Non-native speakers of English who hold nursing qualifications from outside the UK are required to provide evidence of English language competence by achieving a minimum overall score of Band 7 on the International English Language Testing System (IELTS) academic test. To describe the English language required to deal with the daily demands of nursing in the UK. To compare these abilities with the stipulated levels on the language test. A tracking study was conducted with 4 nurses, and focus groups with 11 further nurses. The transcripts of the interviews and focus groups were analysed thematically for recurrent themes. These findings were then compared with the requirements of the IELTS spoken test. The study was conducted outside the participants' working shifts in busy London hospitals. The participants in the tracking study were selected opportunistically;all were trained in non-English speaking countries. Snowball sampling was used for the focus groups, of whom 4 were non-native and 7 native speakers of English. In the tracking study, each of the 4 nurses was interviewed on four occasions, outside the workplace, and as close to the end of a shift as possible. They were asked to recount their spoken interactions during the course of their shift. The participants in the focus groups were asked to describe their typical interactions with patients, family members, doctors, and nursing colleagues. They were prompted to recall specific instances of frequently-occurring communication problems. All interactions were audio-recorded, with the participants' permission,and transcribed. Nurses are at the centre of communication for patient care. They have to use appropriate registers to communicate with a range of health professionals, patients and their families. They must elicit information, calm and reassure, instruct, check procedures, ask for and give opinions,agree and disagree. Politeness strategies are needed to avoid threats to face. They participate in medical team discussions, and provide information. They have to be able to translate between everyday and medical registers. This requires socio-pragmatic competence, much of which is not tested by IELTS. In addition to linguistic knowledge and fluency, nursing requires considerable cultural and pragmatic knowledge and competence. Our findings support arguments for including socio-pragmatic competence in language tests specifically designed for nurses. They also indicate a need for further research to find or design more appropriate assessment, and greater awareness amongst policy makers of the principles of language test design and use.


Totally laparoscopic anterior resection with transvaginal assistance and transvaginal specimen extraction: a technique for natural orifice surgery combined with reduced-port surgery.
Natural orifice specimen extraction (NOSE) has been developed as a means of decreasing the incidence of surgical wound complications. However, NOSE performed using a conventional multiport technique has been reported previously. The current authors performed totally laparoscopic anterior resection with transvaginal specimen extraction (TVSE) using the reduced-port surgery (RPS) technique. The Alexis wound retractor (Applied Medical, Rancho Santa Margarita, CA, USA) and Free Access (Top Corporation, Tokyo, Japan) were attached to the transvaginal route for transvaginal assistance and smooth specimen extraction. The authors documented this simple and safe technique and its short-term results. Data were prospectively collected for five patients who underwent totally laparoscopic anterior resection with TVSE for colorectal cancer between June 2012 and December 2012. A multiport access device (GelPOINT advanced-access platform; Applied Medical) was inserted into the navel, and a 5-mm port was inserted into the right lower quadrant to be used as a drain site. Transverse transvaginal posterior colpotomy then was performed. One ring of an Alexis ring pair was inserted into the peritoneal cavity through the vagina. The other white ring was placed outside of the vagina and then covered with a Free Access to maintain the pneumoperitoneum for insertion of a 12-mm port. Lymph node dissection and transection of the distal colon were performed with transvaginal assistance. The specimen then was extracted transvaginally. After the Alexis had been removed, the vaginal incision was closed transvaginally. End-to-end colorectal anastomosis was performed using the double-stapling technique. Transvaginal extraction was completed in all five cases. The median operation time was 235 min. One case was complicated by chyloperitoneum. The median hospital stay was 6 days. Only one patient required intravenous analgesics once on postoperative day 1. All the patients remained disease free. Totally laparoscopic anterior resection using TVSE with RPS appears to be feasible, safe, and oncologically acceptable for selected cases.


Delayed primary closure versus primary closure for wound management in perforated appendicitis: a prospective randomized controlled trial.
It is still a matter of debate whether delayed primary closure (DPC) of contaminated abdominal incisions reduces surgical site infections compared with a primary closure (PC). The aim of this study was to determine the optimal method of wound closure for patients with perforated appendicitis. A total of 70 patients with perforated appendicitis were included. They were randomized to have their surgical incisions (skin and subcutaneous tissue) either PC or left open with Betadine-soaked gauze packing for DPC on the fifth postoperative day or later if the wound conditions were inappropriate for closure. A wound was considered infected if pus discharged from the incision site. The main outcome measures were the incidence of wound infection and the length of hospital stay (LOS). In the entire series, wound infection developed after incision closure in 21.4% of the patients. The PC group had a higher incidence of wound infection (38.9% vs. 2.9%, p<0.001) and longer LOS (8.4 days vs. 6.3 days, p=0.038). Delayed primary closure is the optimal management strategy for perforated appendicitis wounds. It significantly reduces the wound infection rate and length of stay.


Functional and structural connectome properties in the 5XFAD transgenic mouse model of Alzheimer's disease.
Neurodegeneration in Alzheimer's disease (AD) is associated with amyloid-beta peptide accumulation into insoluble amyloid plaques. The five-familial AD (5XFAD) transgenic mouse model exhibits accelerated amyloid-beta deposition, neuronal dysfunction, and cognitive impairment. We aimed to determine whether connectome properties of these mice parallel those observed in patients with AD. We obtained diffusion tensor imaging and resting-state functional magnetic resonance imaging data for four transgenic and four nontransgenic male mice. We constructed both structural and functional connectomes and measured their topological properties by applying graph theoretical analysis. We compared connectome properties between groups using both binarized and weighted networks. Transgenic mice showed higher characteristic path length in weighted structural connectomes and functional connectomes at minimum density. Normalized clustering and modularity were lower in transgenic mice across the upper densities of the structural connectome. Transgenic mice also showed lower small-worldness index in higher structural connectome densities and in weighted structural networks. Hyper-correlation of structural and functional connectivity was observed in transgenic mice compared with nontransgenic controls. These preliminary findings suggest that 5XFAD mouse connectomes may provide useful models for investigating the molecular mechanisms of AD pathogenesis and testing the effectiveness of potential treatments.


Relevance of prostaglandins in true menstrual migraine.
Eighteen patients suffering from true menstrual migraine and 12 control subjects were studied. We evaluated in different phases of the menstrual cycle and during the migraine crisis the peripheral plasma concentrations of 6-keto-PGF1 alpha (the stable metabolite of PGI2), thromboxane B2 (the stable metabolite of thromboxane A2), PGF2 alpha and PGE2. The mean values of 6-keto-PGF1 alpha in menstrual migraine sufferers are lower than in normal women throughout the whole cycle. The difference between the trends observed in the two groups is statistically significant (p less than 0.05). The plasma levels of TXB2 and of PGF2 alpha are similar in the two groups investigated, both in basal conditions and during the attack. The plasma concentrations of PGE2 are slightly lower in migraineurs in basal conditions than in normals. However, during the crisis they increase significantly (p less than 0.05). In conclusion, among all the parameters considered, PGE2 seems to play the most important role during the pain phase of the attack. The results of the present study suggest that a deficit of PGI2, one of the most important protecting agents against ischemia, might be a typical feature of menstrual migraine and might cause in these patients a vascular hypersensitivity to different ischemic stimuli.


Fucoidan suppresses the gastric cancer cell malignant phenotype and production of TGF-β1 via CLEC-2.
The sulfated polysaccharide fucoidan displays excellent anticancer properties with low toxicity in many kinds of cancers. However, its detailed pharmacological effect and mechanism of action in gastric carcinoma remains unclear. In this study, we found that fucoidan could suppress gastric cancer (GC) cell growth, as well as cell migration and invasion. A cytokine expression screen demonstrated that transforming growth factor beta 1 (TGF-β1) secretion was decreased in fucoidan-treated cells. Fucoidan has been reported to be a platelet agonist for the C-type lectin-like receptor 2 (CLEC-2), and our previous research found that upregulation of CLEC-2 inhibited GC progression. Here, we confirmed that fucoidan, combined with CLEC-2, significantly increased CLEC-2 expression in GC cells via the transcription factor caudal type homeobox transcription factor 2, an important regulator of gut homeostasis. In addition, the inhibitory effect of fucoidan on the GC cell malignant phenotype and TGF-β1 secretion could be restored by knocking down CLEC-2. Thus, our data suggest that fucoidan targets CLEC-2 to exert antitumorigenesis and antimetastatic activity, suggesting that fucoidan is a promising treatment for gastric carcinoma.


Evaluation of bone substitute materials: comparison of flat-panel based volume CT to conventional multidetector CT.
Over the last decade tissue engineering has emerged as a key factor in bone regeneration within the field of cranio-maxillofacial surgery. Despite this in vivo analysis of tissue-engineered-constructs to monitor bone rehabilitation are difficult to conduct. Novel high-resolving flat-panel based volume CTs (fp-VCT) are increasingly used for imaging bone structures. This study compares the potential value of novel fp-VCT with conventional multidetector CT (MDCT) based on a sheep sinus floor elevation model. Calcium-hydroxyapatite reinforced collagen scaffolds were populated with autologous osteoblasts and implanted into sheep maxillary sinus. After 8, 16 and 24 weeks MDCT and fp-VCT scans were performed to investigate the volume of the augmented area; densities of cancellous and compact bone were assessed as comparative values. fp-VCT imaging resulted in higher spatial resolution, which was advantageous when separating closely related anatomical structures (i.e. trabecular and compact bone, biomaterials). Fp-VCT facilitated imaging of alterations occurring in test specimens over time. fp-VCTs therefore displayed high volume coverage, dynamic imaging potential and superior performance when investigating superfine bone structures and bone remodelling of biomaterials. Thus, fp-VCTs may be a suitable instrument for intraoperative imaging and future in vivo tissue-engineering studies.


Detecting common coccinellids found in sorghum using deep learning models.
Increased global production of sorghum has the potential to meet many of the demands of a growing human population. Developing automation technologies for field scouting is crucial for long-term and low-cost production. Since 2013, sugarcane aphid (SCA) Melanaphis sacchari (Zehntner) has become an important economic pest causing significant yield loss across the sorghum production region in the United States. Adequate management of SCA depends on costly field scouting to determine pest presence and economic threshold levels to spray insecticides. However, with the impact of insecticides on natural enemies, there is an urgent need to develop automated-detection technologies for their conservation. Natural enemies play a crucial role in the management of SCA populations. These insects, primary coccinellids, prey on SCA and help to reduce unnecessary insecticide applications. Although these insects help regulate SCA populations, the detection and classification of these insects is time-consuming and inefficient in lower value crops like sorghum during field scouting. Advanced deep learning software provides a means to perform laborious automatic agricultural tasks, including detection and classification of insects. However, deep learning models for coccinellids in sorghum have not been developed. Therefore, our objective was to develop and train machine learning models to detect coccinellids commonly found in sorghum and classify them according to their genera, species, and subfamily level. We trained a two-stage object detection model, specifically, Faster Region-based Convolutional Neural Network (Faster R-CNN) with the Feature Pyramid Network (FPN) and also one-stage detection models in the YOLO (You Only Look Once) family (YOLOv5 and YOLOv7) to detect and classify seven coccinellids commonly found in sorghum (i.e., Coccinella septempunctata, Coleomegilla maculata, Cycloneda sanguinea, Harmonia axyridis, Hippodamia convergens, Olla v-nigrum, Scymninae). We used images extracted from the iNaturalist project to perform training and evaluation of the Faster R-CNN-FPN and YOLOv5 and YOLOv7 models. iNaturalist is an imagery web server used to publish citizen's observations of images pertaining to living organisms. Experimental evaluation using standard object detection metrics, such as average precision (AP), firstname.lastname@example.com, etc., has shown that the YOLOv7 model performs the best on the coccinellid images with an firstname.lastname@example.com as high as 97.3, and AP as high as 74.6. Our research contributes automated deep learning software to the area of integrated pest management, making it easier to detect natural enemies in sorghum.


Restoration of the endodontically treated tooth: an online study guide.
The Editorial Board of the Journal of Endodontics has developed a literature-based study guide of topical areas related to endodontics. This study guide is intended to give the reader a focused review of the essential endodontic literature and does not cite all possible articles related to each topic. Although citing all articles would be comprehensive, it would defeat the idea of a study guide. This section will focus on restoration of endodontically treated teeth.


Effects of crosslinking on the thermal stability of hemoglobin. I. The use of bis(3,5-dibromosalicyl) fumarate.
The double-headed aspirin, bis(3,5-dibromosalicyl) fumarate, has been used to crosslink hemoglobin A between Lys 82 beta 1 and Lys 82 beta 2 (J. A. Walder et al. (1979) Biochemistry 18,4265). Denaturation experiments were used to compare the stability of this crosslinked protein to that of hemoglobin A. Thermal denaturations, done in 0.01 M 4-morpholine-propanesulfonic acid, pH 7, containing 0.9 M guanidine to prevent precipitation at high temperatures, were monitored by changes in absorbance between 190 and 650 nm using a diode array spectrophotometer. The sample was heated from 25 to 70 degrees C at 0.3 degrees C/min. The data were analyzed by using both a two-state model and a novel first derivative method. As expected, methemoglobin A had a single, broad transition with a midpoint of 40.7 degrees C. The crosslinked methemoglobin showed a transition at 57.1 degrees C. Two minor transitions, one of which was apparently due to residual unmodified hemoglobin, were also observed in the crosslinked sample. Thus, a single crosslink between only two of the four subunits can lead to a significantly more stable molecule. These results can be explained by Le Chatelier's principle, since crosslinking prevents dissociation of the beta-subunits and, thereby, holds the entire tetramer together.


{μ-2,2'-(Ethane-1,2-di-yl)bis-[4,6-bis-(tri-methyl-sil-yl)-1,3-di-hydro-cyclo-penta-[c]pyrrol-5-one]}bis-[tri-carbonyl-iron(0)].
The binuclear title compound, [Fe2(C28H48N2O2Si4)(CO)6], consists of two central iron(0) atoms, each of them surrounded by a cyclo-penta-dienone moiety and three carbonyl ligands in a three-legged piano-stool shape. Furthermore, the bis-(cyclo-penta-dienone) ligand acts as a bridge between the two metal atoms.


Convenient synthesis of polyfunctional dihydrothiophenes with tandem reaction of 1,3-thiazolidinedione, aldehyde, arylamine and ethyl cyanoacetate.
New, highly-functionalized dihydrothiophenes are conveniently synthesized from the novel tandem, four-component reactions of 1,3-thiazolidinedione, aldehyde, arylamine, and ethyl cyanoacetate, catalyzed by triethylamine. The reaction mechanism involves the use of Knoevenagel condensation, Michael addition, and ring-opening of 1,3-thiazolidinedione, followed by intramolecular ring closure process. The reaction is diastereoselective and only trans-2,3-dihydrothiophenes were produced in moderate yields. The functionalized dihydrothiophenes can be converted efficiently to the corresponding thiophenes by DCC dehydrogenation reaction.


Quality and readability of online information on dental treatment for snoring and obstructive sleep apnea.
To evaluate quality and readability of online information on dental treatment for snoring and obstructive sleep apnea. An Internet search was done using three engines (Bing, Google, and Yahoo) with the combination of terms, "snoring sleep apnea dental treatment". The first 100 sites from the search of each engine were screened. Subject sites were evaluated with Health on the Net(HON) criteria, Journal of American Medical Association(JAMA) benchmarks, DISCERN, Ensuring Quality Information for Patients(EQIP), Flesch-Kincaid Grade level and Flesch Reading Ease(FRE) score. One hundred and thirty websites were evaluated. The HON, DISCERN, EQIP, and FRE score were each 39.4%, 47.3%, 49.7%, and 51.6% of the maximum possible score, respectively. According to JAMA benchmarks fewer than 50% of the sites displayed attribution and currency. There was only one site displaying the HON seal. HON score, DISCERN score and EQIP score showed significant inter-correlation. Based on this study, the current quality and readability of searchable websites on dental treatment for snoring and sleep apnea are low and poorly maintained on average. Clinicians should be able to evaluate and give accurate online information on this issue to patients.


Tailored corneo-conjunctival autografting in primary and secondary pterygium surgery.
To describe the outcomes of a novel technique for pterygium removal: tailored corneo-conjunctival autograft, which offers the advantages of better postoperative cosmetic outcomes and recurrence prevention. This retrospective interventional noncomparative study included 420 eyes in 370 patients (ages 25-60 years) (127 women, 243 men). We divided the patients into 2 groups. The first group included 348 primary pterygium; the second group included 72 recurrent pterygium. All underwent the same type of corneo-conjunctival autograft surgery from April 2009 to March 2014. The average follow-up period was 12 months. The main outcome measures were to assess pain after surgery, conjunctival healing, cosmetic appearance, and pterygium recurrence at the end of follow-up. In both groups, the graft donor site healed promptly without excessive scarring. No patient complained of pain during first week after surgery, except for mild discomfort. No major complications were observed such as infection or graft necrosis. In the first group, 2 patients had graft retraction towards the nasal side and were successfully managed conservatively. One patient had Tenon granuloma, which was removed surgically. Recurrence during the follow-up period was seen in one patient (0.2%). In the second group, no recurrent pterygium cases were observed. The proposed type of corneo-conjunctival autograft offers the advantage of better postoperative cosmetic outcomes. This new technique is effective for surgical management of both primary and recurrent pterygium and preventing its recurrences.


A review of anorexia induced by T-2 toxin.
The presence of anorexia in animals is the most well-known clinical symptom of T-2 toxin poisoning. T-2 toxin is the most characteristic type A toxin in the trichothecene mycotoxins. The consumption of T-2 toxin can cause anorexic response in mice, rats, rabbits, and other animals. In this review, the basic information of T-2 toxin, appetite regulation mechanism and the molecular mechanism of T-2 toxin-induced anorectic response in animals are presented and discussed. The objective of this overview is to describe the research progress of anorexia in animals produced by T-2 toxin. T-2 toxin mainly causes antifeedant reaction through four pathways: vagus nerve, gastrointestinal hormone, neurotransmitter and cytokine. This review aims to give an academic basis and useable reference for the prevention and treatment of clinical symptoms of anorexia in animals resulting from T-2 toxin.


The outcomes of endoscopic dacryocystorhinostomy in children: A systematic review.
To systematically review and discuss the published results about the application of endoscopic dacryocystorhinostomy in treating children with nasolacrimal duct obstruction. In October 2014 an appropriate string was run on PubMed to retrieve all relevant articles. A cross-check was performed by two of the authors on abstracts and full-text articles found using the selected inclusion and exclusion criteria. A non-comparative meta-analysis concerning the procedures' rate of success and failure was performed. Fourteen studies were identified comprising a total of 346 subjects affected by nasolacrimal duct obstruction (unilateral or bilateral). Overall there were 393 surgical procedures, all performed with an exclusive endoscopic approach. The average length of follow-up was reported in twelve studies resulting 15.2 months and ranging from 3 to 27.1 months. On the basis of our statistical analysis the mean (95% CI) rate of failure was 0.14 (0.09-0.21). The mean (95% CI) rate of success resulted 0.87 (0.80-0.91). Although in young patients the nasal anatomy is more complex and narrow than in adults our review showed as the endoscopic dacryocystorhinostomy allows similar results in terms of success compared to the external approach.


Effects of supplemental vitamin E during the mature period on the reproduction performance of Taiwan Native Chicken cockerels.
One-day-old Taiwan native male chicks were fed with maize-soybean rearing diets without supplemental vitamin E to 23 weeks of age. From 23 to 52 weeks of age, the cockerels (n = 90) were assigned at random to 5 dietary treatments and fed with maize-soybean diets supplemented with 0, 20, 40, 80 and 160 mg/kg of vitamin E (dl-alpha-tocopherol acetate). Pullets (225) of the same age were fed with standard diets throughout. They were artificially inseminated with one dose of 0.04 ml/bird intact and 5-fold diluted pooled semen at 31 to 43 weeks of age and at 49 weeks of age, respectively. The criteria evaluated included: semen quality, fertility and maximum and effective duration of fertility, blood characteristics, body and testes weight. Supplemental vitamin E did not affect cockerels' effective duration of fertility and percentage of fertility. However, when pullets were inseminated with diluted semen, supplementing 160 mg/kg vitamin E increased the maximum duration of fertility at 49 weeks of age. Cockerels receiving 40 to 160mg/kg supplements had higher sperm viability and motility after 39 weeks of age and those fed 80 mg/kg had higher sperm concentration at 39 weeks of age. Cockerels receiving supplements of more than 40 mg/kg vitamin E had higher body weight gain. Plasma cholesterol and testosterone were not affected by supplemental vitamin E. However, plasma luteinising hormone (LH) concentration was lower in cockerels fed 160 mg/kg. Lack of supplemental vitamin E over 39 weeks was associated with lower semen quality but did not reduce the proportion of fertile eggs laid by inseminated hens, perhaps because the insemination dose compensated for low sperm quality. We found that the maximum duration of fertility might be improved by supplementing 160 mg/kg vitamin E at 49 weeks of age.


Digestive disease week 2000. American Association for the Study of Liver Diseases.
The latest advances in hepatology were presented in oral and poster presentations. In order to cover the varying subspecialties, the sessions were divided into various sections including 'Acute Liver Failure and Artificial Liver Support', 'Biliary Tract and Immunologic Liver Diseases', 'Cellular and Molecular Biology', 'Clinical and Experimental Hepatobiliary Surgery', 'Hepatotoxicity and Cell Death', 'Transport and Biliary Physiology', 'Viral Hepatitis', 'Evaluation and Treatment of Biliary Disease', 'Necrosis/Apoptosis', 'Portal Hypertension', 'Blood Flow and Vascular Disorders of Cirrhosis', 'Liver Transplantation', 'Fibrogenesis', 'Hepatocellular Carcinoma', 'Metabolism and Genetic Disease', and 'Public Policy, Epidemiology and Decision Analysis'. Drug therapy focused on treatments for viral hepatitis, autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis, and recurrent viral disease following liver transplant. High dose interferon therapy or various combinations of interferon/ribavirin (ICN Pharmaceuticals Inc) therapy seem to offer the best current therapy for chronic HCV. PEGylated interferon (F Hoffmann-La Roche Ltd) offers hope for treatment and histologic improvement in patients with chronic HCV. Following liver transplantation, combination interferon/ribavirin therapy may also find success, but caution with new potent immunosuppressant monoclonal antibodies is advised. For HBV, intramuscular H-BIG (NABI) appears to be effective and less costly than iv H-BIG administration following liver transplantation. Percutaneous radiofrequency ablation may hold promise over conventional ethanol injection therapy for small hepatocellular carcinoma. Autoimmune hepatitis may respond to tacrolimus therapy whereas budesonide therapy did not provide any advantage to prednisone therapy. For primary biliary cirrhosis, eicosapentate and ursodeoxycholic acid may provide benefit to some patients while silymarin from milk thistle did not provide any additional benefit. In primary sclerosing cholangitis, high dose ursodeoxycholic acid may provide benefit. Ursodeoxycholic acid may also provide benefit for mothers with intrahepatic cholestasis of pregnancy by decreasing pruritus, lowering laboratory values and allowing deliveries to occur closer to term.


The prescribing of Chinese herbal products in Taiwan: a cross-sectional analysis of the national health insurance reimbursement database.
The consumption of Chinese herbal products (CHPs) is increasing exponentially. However, the scientific evidence is lacking and there is an urgent requirement for detailed pharmacoepidemiological information on CHP usage. This study was to investigate CHP prescription patterns in Taiwan. We carried out a cross-sectional analysis on a cohort of 200,000 patients based on 2004 data from the National Health Insurance (NHI) reimbursement database. Data mining techniques were applied to explore CHP co-prescription patterns. A total of 46,938 patients had been prescribed CHPs on at least one occasion in 2004. Patients using CHPs were generally female and middle-aged, made more outpatient visits, had fewer hospitalizations and consumed more medical resources than non-users of CHPs. A total of 1,073,030 CHPs were contained within 220,123 prescriptions, for which acute nasopharyngitis was the most common indication. Yan hu suo and Jia Wei Xiao Yao San were the most frequently prescribed single herb (SH) and herbal formula (HF), respectively. The results of the data mining showed that the best predictions were provided by co-prescriptions of 'Mo yao and Ru xiang', 'Ye jiao teng and Suan Zao Ren Tan' and 'Dang Gui Nian Tong Tang and Shu Jing Huo Xue Tang' in the groups of SH-SH, SH-HF and HF-HF, respectively. This study provides national-level CHP prescription profiles and utilization rates, and documents, for the first time, HF-HF prescription combinations in Chinese medicine (CM) practices in Taiwan. We conclude that more studies are needed to validate the safety and effectiveness of CHP prescriptions.


The 'bother' of obstructed defecation.
To examine the relationship of visual analog scale (VAS) 'bother' scores for obstructed defecation (OD) with demographic data, physical examination and sonographic findings of the posterior compartment. All patients seen at a urogynecology clinic between January and October 2013 were included. Patients were diagnosed with OD if they had any of the following: incomplete bowel emptying, straining with bowel movement or need for digitation. Patients used a VAS to rate OD bother on a scale of 0-10 (0, no bother; 10, worst imaginable bother). For each patient, a comprehensive history was obtained, the International Continence Society Pelvic Organ Prolapse Quantification was performed and four-dimensional translabial ultrasound volumes were recorded on maximal Valsalva maneuver. Linear and multiple regression models were used to correlate bother VAS scores with demographic, clinical and sonographic findings. Among 265 patients included in the analysis, 61% had OD symptoms with a mean VAS bother score of 5.6. OD bother scores were associated with a history of previous prolapse surgery (P = 0.0001), previous hysterectomy (P = 0.0006), descent of the posterior compartment (Bp; P = 0.004) and hiatal dimensions (Pb and Gh + Pb; P = 0.006 and P = 0.004). OD bother was associated with the following sonographic findings: true rectocele (P = 0.01), depth of rectocele (P = 0.04), descent of rectal ampulla (P = 0.02), enterocele (P = 0.03) and rectal intussusception (P < 0.0001). VAS bother scores are associated with both clinical and sonographic measures of posterior compartment descent. Rectal intussusception was most likely to result in highly bothersome symptoms of OD. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.


Polycation-detachable nanoparticles self-assembled from mPEG-PCL-g-SS-PDMAEMA for in vitro and in vivo siRNA delivery.
Long circulation, cell internalization, endosomal escape and small interfering RNA (siRNA) release to the cytoplasm are the prerequisite considerations for siRNA delivery vectors. Herein, a kind of sheddable nanoparticles (NPs) with micelle architecture for siRNA delivery were fabricated by using an intracellular-activated polycation-detachable copolymer (PECssD), which was prepared by introducing highly reducing environment-responsive disulfide linkages between PEGylated polycaprolactone (PCL) and the grafted polycation, poly(2-dimethylaminoethyl methacrylate) (PDMAEMA). The architecture of PECssD self-assembled NPs includes a biodegradable hydrophobic PCL core, a PEG shield and a detachable comb-like polycation surface. The stable nanosized complexes of PECssD NPs with siRNA, termed PECssD/siRNA micelleplexes, were formed, which could prolong circulation, improve accumulation and retention in tumor tissue, and be favorable for internalization. In particular, the cleavage of the disulfide linkages in the intracellular microenvironment and the subsequent dissociation of the PDMAEMA/siRNA polyplexes from the PEGylated PCL cores of PECssD/siRNA micelleplexes were also confirmed, which facilitated the endosomal escape and the efficient release of siRNA. As a result, the distribution of siRNA in cytoplasm was enhanced and subsequently promoted the efficiency of siRNA in gene silencing. Furthermore, systemic administration of the NPs carrying siPlk1 (polo-like kinase 1 specific siRNA) induced a tumor-suppressing effect in the HeLa-Luc xenograft murine model. Therefore, the devised strategy of the polycation-detachable copolymer PECssD NPs could address the requirements of the multistep systemic delivery process of siRNA. The hydrophobic core of the PECssD/siRNA micelleplexes is expected to entrap antitumor drugs or other therapeutic agents for combined therapies.


Consequences of anatomic changes and respiratory motion on radiation dose distributions in conformal radiotherapy for locally advanced non-small-cell lung cancer.
To determine the effect of interfractional changes in anatomy on the target and normal tissue dose distributions during course of radiotherapy in non-small-cell lung cancer patients. Weekly respiration-correlated four-dimensional computed tomography scans were acquired for 10 patients. Original beam arrangements from conventional and inverse treatment plans were transferred into each of the weekly four-dimensional computed tomography data sets, and the dose distributions were recalculated. Dosimetric changes to the target volumes and relevant normal structures relative to the baseline treatment plans were analyzed by dose-volume histograms. The overall difference in the mean +/- standard deviation of the doses to 95% of the planning target volume and internal target volume between the initial and weekly treatment plans was -11.9% +/- 12.1% and -2.5% +/- 3.9%, respectively. The mean +/- standard deviation change in the internal target volume receiving 95% of the prescribed dose was -2.3% +/- 4.1%. The overall differences in the mean +/- standard deviation between the initial and weekly treatment plans was 3.1% +/- 6.8% for the total lung volume exceeding 20 Gy, 2.2% +/- 4.8% for mean total lung dose, and 34.3% +/- 43.0% for the spinal cord maximal dose. Serial four-dimensional computed tomography scans provided useful anatomic information and dosimetric changes during radiotherapy. Although the observed dosimetric variations were small, on average, the interfractional changes in tumor volume, mobility, and patient setup was sometimes associated with dramatic dosimetric consequences. Therefore, for locally advanced lung cancer patients, efforts to include image-guided treatment and to perform repeated imaging during the treatment course are recommended.


Acanthamoeba culbertsoni isolated from a clinical case with intraocular dissemination: Structure and in vitro analysis of the interaction with hamster cornea and MDCK epithelial cell monolayers.
Acanthamoeba culbertsoni trophozoites, previously isolated from a human keratitis case with severe intraocular damage, were maintained in axenic culture. Co-incubation of amoebae with MDCK cell monolayers demonstrated an apparent preference of the amoebae to introduce themselves between the cells. The trophozoites appeared to cross the cell monolayer through the tight junctions, which resulted in decreased trans-epithelial resistance (TER) measurements. Unexpectedly, after co-incubation of amoebae with hamster corneas, we observed that the trophozoites were able to cross the different cell layers and reach the corneal stroma after only 12 h of interaction, in contrast to other Acanthamoeba species. These observations suggest that this A. culbertsoni isolate is particularly pathogenic. Further research with diverse methodologies needs to be performed to explain the unique behavior of this Acanthamoeba strain.


Charting the trajectory of forgetting: Insights from a working memory period paradigm.
Working memory capacity is commonly measured in terms of its item span, and much less often in terms of its time span, or "period." The former measures how many items can be stored in working memory when carrying out episodes of concurrent processing. The latter complements this by determining the duration of processing episodes that can be tolerated while successfully storing a fixed number of items. We investigated the generality of previous evidence that working memory period varies with the distribution of longer and shorter processing episodes within a trial, and that notwithstanding such differences, a global measure of period is a reliable predictor of children's educational attainment. We describe data from 184 children, between 7 and 11 years of age, who completed variants of an operation period task with different distributions of processing episodes together with measures of scholastic attainment. Individual differences in period scores were consistent over two test sessions, and were predictive of reading and number skills. We replicated previous effects of the order of longer and shorter processing episodes, but found that they did not generalize fully to other manipulations of order. The results point to the contribution of subtle within-trial sequence configurations for working memory. We make the case for a broader view of what constrains working memory than exists in current models.


Patch-based generative adversarial neural network models for head and neck MR-only planning.
To evaluate pix2pix and CycleGAN and to assess the effects of multiple combination strategies on accuracy for patch-based synthetic computed tomography (sCT) generation for magnetic resonance (MR)-only treatment planning in head and neck (HN) cancer patients. Twenty-three deformably registered pairs of CT and mDixon FFE MR datasets from HN cancer patients treated at our institution were retrospectively analyzed to evaluate patch-based sCT accuracy via the pix2pix and CycleGAN models. To test effects of overlapping sCT patches on estimations, we (a) trained the models for three orthogonal views to observe the effects of spatial context, (b) we increased effective set size by using per-epoch data augmentation, and (c) we evaluated the performance of three different approaches for combining overlapping Hounsfield unit (HU) estimations for varied patch overlap parameters. Twelve of twenty-three cases corresponded to a curated dataset previously used for atlas-based sCT generation and were used for training with leave-two-out cross-validation. Eight cases were used for independent testing and included previously unseen image features such as fused vertebrae, a small protruding bone, and tumors large enough to deform normal body contours. We analyzed the impact of MR image preprocessing including histogram standardization and intensity clipping on sCT generation accuracy. Effects of mDixon contrast (in-phase vs water) differences were tested with three additional cases. The sCT generation accuracy was evaluated using mean absolute error (MAE) and mean error (ME) in HU between the plan CT and sCT images. Dosimetric accuracy was evaluated for all clinically relevant structures in the independent testing set and digitally reconstructed radiographs (DRRs) were evaluated with respect to the plan CT images. The cross-validated MAEs for the whole-HN region using pix2pix and CycleGAN were 66.9 ± 7.3 vs 82.3 ± 6.4 HU, respectively. On the independent testing set with additional artifacts and previously unseen image features, whole-HN region MAEs were 94.0 ± 10.6 and 102.9 ± 14.7 HU for pix2pix and CycleGAN, respectively. For patients with different tissue contrast (water mDixon MR images), the MAEs increased to 122.1 ± 6.3 and 132.8 ± 5.5 HU for pix2pix and CycleGAN, respectively. Our results suggest that combining overlapping sCT estimations at each voxel reduced both MAE and ME compared to single-view non-overlapping patch results. Absolute percent mean/max dose errors were 2% or less for the PTV and all clinically relevant structures in our independent testing set, including structures with image artifacts. Quantitative DRR comparison between planning CTs and sCTs showed agreement of bony region positions to <1 mm. The dosimetric and MAE based accuracy, along with the similarity between DRRs from sCTs, indicate that pix2pix and CycleGAN are promising methods for MR-only treatment planning for HN cancer. Our methods investigated for overlapping patch-based HU estimations also indicate that combining transformation estimations of overlapping patches is a potential method to reduce generation errors while also providing a tool to potentially estimate the MR to CT aleatoric model transformation uncertainty. However, because of small patient sample sizes, further studies are required.


Effect of roughness and acidic medium on wear behavior of dental resin composite.
The aim of the study was to investigate whether the citric acid and rough surface have a synergistic effect leading to severe wear behavior of resin composite. Disk-shaped (Ø15 × 1.5 mm) specimens of resin composite (n = 12) with different initial roughness were prepared. Reciprocating ball-on-flat wear tests were performed under distilled water and citric acid (pH = 5.5) respectively. The coefficient of friction (COF), wear volume loss, and duration of the running-in period were quantified to assess the wear performance. And the values were analyzed with one-way ANOVA (α = 0.05). Regression analysis was applied to examine the influence of Ra values and mediums on the wear data. The wear morphology was analyzed by scanning electron microscopy and a 3D profilometer. The average COF was higher in distilled water than in citric acid but was independent of the surface roughness. For the composite, the volume loss of worn area and running-in period increased with surface roughness when tested under distilled water. However, these increasing trends were not found in citric acid. All specimens exhibited mild wear behavior with low COF and less superficial abrasion in acidic medium. The effect of initial roughness on wear behavior depends on the medium. In distilled water, resin composites with high initial roughness exhibit a longer running-in time, which eventually leads to a significant increase in material loss. The adverse effects of high roughness can be alleviated by the lubrication of citric acid, which can maintain a mild wear behavior regardless of initial surface roughness.


Metabolism of acetaldehyde in human and baboon renal cortex. Ethanol synthesis by isolated baboon kidney-cortex tubules.
Acetaldehyde (1-20 mM) was metabolized at high rates and in a dose-dependent manner in isolated human and baboon kidney-cortex tubules. Acetaldehyde removal was accompanied by a large accumulation of acetate in both human and baboon tubules. By contrast, a large synthesis of ethanol was observed only in baboon tubules. Consistent with the latter finding, ethanol was found to be metabolized at significant rates in baboon but not human tubules. In the tubules from both species, a significant fraction of the acetaldehyde removed was also completely oxidized to CO2 and H2O. These results suggest that, in both man and baboon, the kidneys participate in the in vivo metabolism of acetaldehyde; they also suggest that, in contrast with the human kidneys, the baboon kidneys contribute to the detoxication of circulating ethanol.


Faraday-Cage-Type Electrochemiluminescence Immunoassay: A Rise of Advanced Biosensing Strategy.
Electrochemiluminescence immunoassays are usually carried out through "on-electrode" strategy, i.e., sandwich-type immunoassay format, the sensitivity of which is restricted by two key bottlenecks: (1) the number of signal labels is limited and (2) only a part of signal labels could participate in the electrode reaction. In this Perspective, we discuss the development of an "in-electrode" Faraday-cage-type concept-based immunocomplex immobilization strategy. The biggest difference from the traditional sandwich-type one is that the designed "in-electrode" Faraday-cage-type immunoassay uses a conductive two-dimensional (2-D) nanomaterial simultaneously coated with signal labels and a recognition component as the detection unit, which could directly overlap on the electrode surface. In such a case, electrons could flow freely from the electrode to the detection unit, the outer Helmholtz plane (OHP) of the electrode is extended, and thousands of signal labels coated on the 2-D nanomaterial are all electrochemically "effective." Thus, then, the above-mentioned bottlenecks obstructing the improvement of the sensitivity in sandwich-type immunoassay are eliminated, and as a result a much higher sensitivity of the Faraday-cage-type immunoassay can be obtained. And, the applications of the proposed versatile "in-electrode" Faraday-cage-type immunoassay have been explored in the detection of target polypeptide, protein, pathogen, and microRNA, with the detection sensitivity improved tens to hundreds of times. Finally, the outlook and challenges in the field are summarized. The rise of Faraday-cage-type electrochemiluminescence immunoassay (FCT-ECLIA)-based biosensing strategies opens new horizons for a wide range of early clinical identification and diagnostic applications.


Time-resolved structural analysis of an RNA-cleaving DNA catalyst.
The 10-23 DNAzyme is one of the most prominent catalytically active DNA sequences1,2. Its ability to cleave a wide range of RNA targets with high selectivity entails a substantial therapeutic and biotechnological potential2. However, the high expectations have not yet been met, a fact that coincides with the lack of high-resolution and time-resolved information about its mode of action3. Here we provide high-resolution NMR characterization of all apparent states of the prototypic 10-23 DNAzyme and present a comprehensive survey of the kinetics and dynamics of its catalytic function. The determined structure and identified metal-ion-binding sites of the precatalytic DNAzyme-RNA complex reveal that the basis of the DNA-mediated catalysis is an interplay among three factors: an unexpected, yet exciting molecular architecture; distinct conformational plasticity; and dynamic modulation by metal ions. We further identify previously hidden rate-limiting transient intermediate states in the DNA-mediated catalytic process via real-time NMR measurements. Using a rationally selected single-atom replacement, we could considerably enhance the performance of the DNAzyme, demonstrating that the acquired knowledge of the molecular structure, its plasticity and the occurrence of long-lived intermediate states constitutes a valuable starting point for the rational design of next-generation DNAzymes.