Development of chitosan nanocapsules containing essential oil of Matricaria chamomilla L. for the treatment of cutaneous leishmaniasis.
Matricaria chamomilla L. has been used for centuries in many applications, including antiparasitic activity. Leishmaniasis is a parasitic disease, with limited treatments, due to high cost and toxicity. Thus, there is a need to develop new treatments, and in this context, natural products are targets of these researches. We report the development of chitosan nanocapsules containing essential oil of M. chamomilla (CEO) from oil-in-water emulsions using chitosan modified with tetradecyl chains as biocompatible shell material. The nanocapsules of CEO (NCEO) were analyzed by optical microscopy and dynamic light scattering, which revealed spherical shape and an average size of 800 nm. Successful encapsulation of CEO was further confirmed by fluorescence microscopy observations taking advantage of the autofluorescence properties of CEO. The encapsulation efficiency was around 90%. The entrapment of CEO reduced its cytotoxicity towards normal cells. On the other hand, the CEO was active against promastigotes and intracellular amastigotes, exhibiting IC50 of 3.33 μg/mL and 14.56 μg/mL, respectively, while NCEO showed IC50 for promastigotes of 7.18 μg/mL and for intracellular amastigotes of 14.29 μg/mL. These results demonstrate that encapsulation of CEO in nanocapsules using an alkylated chitosan biosurfactant as a "green" stabilizer is a promising therapeutic strategy to treat leishmaniasis.


Measuring Hsp72 (HSPA1A) by indirect sandwich ELISA.
The enzyme-linked immunosorbent assay (ELISA) is an immunological technique which is used to determine the presence or quantity of an antigen within a sample. ELISAs rely on the use of at least one antibody (Ab) specific for the antigen being measured. This antibody is covalently linked to an enzyme which is detected through the use of an enzymatic substrate, which can be colorimetric, fluorogenic, or chemiluminescent. The ELISA for Hsp72 described here is a typical indirect sandwich ELISA, which can be used for measuring Hsp72 from cellular/tissue extracts, tissue culture supernatant, and serum. Typically, a 96-well ELISA plate is coated with a specific antibody which captures Hsp72 from the sample, and another antibody specific for a different Hsp72 epitope is used to detect Hsp72. An enzyme-labelled species-specific antibody conjugate is then applied which is consequently detected using a colorimetric enzyme substrate. The quantity of Hsp72 present in the samples is interpolated using a standard curve of known amounts of pure Hsp72.


The role of causal structure in implicit evaluation.
Causal relationships, unlike mere co-occurrence, allow humans to obtain rewards and avoid punishments by intervening on their environment. Accordingly, explicit (controlled) evaluations of stimuli encountered in the environment are known to be sensitive to causal relationships above and beyond mere co-occurrence. In this project, we conduct stringent tests of whether implicit (automatic) evaluation also reflects causal relationships and begin to probe the representational mechanisms underlying such sensitivity. Participants (N = 4836) observed causal events during which two stimuli were equally contingent with positive or negative outcomes but only one of them was causally responsible for these outcomes. Across 6 studies, varying in design and amount of verbal scaffolding provided, differences in causal status consistently guided not only explicit measures of evaluation (Likert and slider scales; Bayes Factor meta-analysis: Cohen's d = 0.28, BF10 > 1046) but also their implicit counterparts (Implicit Association Tests; Bayes Factor meta-analysis: Cohen's d = 0.22, BF10 > 1029). However, unlike their explicit counterparts, implicit evaluations were not sensitive to causal relationships that had to be flexibly derived by combining disparate past experiences. Taken together, these studies suggest that implicit evaluations are sensitive to causal information. Such sensitivity seems to be mediated via precompiled, causally informed value representations rather than online computations over a causal model.


Diving in: Using a "Shark Tank" approach to teach business skills to future DNP leaders.
Doctor of Nursing Practice (DNP) education prepares graduates to lead clinical improvement and innovation across practice settings. Advanced clinical knowledge, leadership skills, and the development of quality/safety competencies uniquely prepare the DNP program graduates to drive organizational change. Adding business and financial competencies to the skill set of DNP graduates strengthens the impact and value of their role on financial, quality, and operational outcomes. The Organizational Systems and Healthcare Financing course in a DNP program was redesigned to engage learners using an innovative approach to teach business and financial principles. This paper aims to (a) describe a novel "Shark Tank" approach whereby students develop and "pitch" their business proposals to a panel of healthcare executives; (b) share examples of impactful change projects by student teams; (c) report DNP course and program evaluations including students' satisfaction and perceptions of value and knowledge gained in business principles; and (d) report opportunities for bidirectional mentorship, faculty recruitment, and succession planning. The success of this innovative team-based approach for teaching business/financial skills better prepares future DNP leaders and has implications for other DNP programs. Using this teaching strategy created opportunities for faculty recruitment, succession planning, and bidirectional mentorship of DNP-prepared nurse leaders.


A preliminary experiment on long-term memory with realistic and abstract visual patterns in uniltateral focal hemisphere-damaged patients.
Sixty-seven focal hemisphere-damaged patients (38 to the left hemisphere and 29 to the right hemisphere) were tested for forgetting of realistic and abstract visual patterns over a 40-sec to 5-min interval by means of a recognition task. No forgetting took place in any group, even if abstract patterns proved to be poorly recognized both at 40 sec and at 5 min. The authors conclude that focal neocortical unilateral lesions do not significantly hamper the semantic code processes involved in the Long-Term Memory of the patterns employed in this experiment.


Ninety-Six Hour Wireless Esophageal pH Study in Patients with GERD Shows that Restrictive Diet Reduces Esophageal Acid Exposure.
Prolonged (96 h) pH monitoring may explore the effect of diet on pH and symptoms in patients with GERD. To assess the usefulness of a 96 h esophageal pH study in patients with GER symptoms under different diets (pro- and anti-GER). Prospective study of 66 patients with GERD undergoing wireless 96 h pH monitoring. Two-day periods, one on liberal (pro-reflux) and another on restricted (anti-reflux) diet assessed esophageal acid exposure and symptoms. The primary end point was normalization of acid exposure time while on restricted diet. Secondary end point was a > 50% reduction in symptoms with restricted diet. Normal (pH time < 4 of < 6%) was found in 34 patients (51.5%) while on the initial 48 h (liberal) diet [median % time < 4: 3.2 (95% CI, 1.9, 4.0)] and remained normal while on restricted diet [median % time < 4: 2.6 (95% CI, 0.8, 3.4)]. Abnormal acid exposure (% pH time < 4: > 6%) was found in 32 patients (48.5%) while on initial 48 h liberal diet [median % time < 4: 10.5, (95% CI 8.9, 12.6)], and decreased significantly with restricted diet [median % time < 4: 4.5 (95% CI 3.1, 7.3)] (p = 0.001), and normalized with anti-GERD diet in 21 patients (65.6%). Only 11/66 patients were candidates for proton pump inhibitor (PPI) use; 34 had either normal pH studies or normalized them with restricted diet (n = 21). Symptoms did not improve with restricted diet. The 96-h esophageal pH study tests for GERD under pro- and anti-GER diets and allows minimization of PPI therapy to only 16.6% of patients.


Genetic information and life insurance: a 'real' risk?
Public concern about genetic discrimination, particularly access to insurance following genetic testing, has been reported in the literature. This paper aims to separate myths from realities regarding genetic discrimination in life insurance and to underline the positive aspects of allowing insurers access to relevant genetic information for underwriting purposes. We present a review of the literature pertinent to discrimination in life insurance and a comparative analysis of industries guidelines. There are few reported cases in the literature of validated genetic discrimination. However, the benefits to be gained by allowing insurers access to relevant genetic data could justify fostering a more active role in the use of genetic information by insurance companies.


Determination of absolute configuration using single crystal X-ray diffraction.
Single crystal X-ray crystallography is the most powerful structural method for the determination of the 3D structures of molecules. While the results of a routine diffraction experiment readily provide unambiguous determination of the relative configuration of all stereogenic centers in the molecule, determination of absolute configuration is more challenging. This chapter provides some helpful tips towards increasing the chances of success in the determination of the absolute configuration of a chiral, enantiomerically pure natural product using X-ray crystallography.


Sweat contamination induced surgical site infections after spine surgery: Three case reports and literature review.
Surgical site infection (SSI) is one of the most intractable complications following spine surgery during the early postoperative stage. Elderly (age > 70 years), body mass index > 30, smoking, diabetes mellitus, coronary artery disease, chronic obstructive pulmonary disease, anemia, low serum albumin, operation time > 3 h, and perioperative blood loss > 500 mL are the common risk factors of SSI after spine surgery. However, there are few published reports about sweat contamination induced surgical site infections with Staphylococcus epidermidis up to date. Staphylococcus epidermidis is a permanent member of the normal human microbiota and has emerged as an important opportunistic pathogen in SSI. We aim to detect the influence of sweat infiltration on SSI with Staphylococcus epidermidis and effective management. A 73-year-old male, a 54-year-old male and a 73-year-old female were admitted to our hospital. All of them underwent posterior compression and fusion surgery with internal fixation and got surgical site infection after primary surgery. Two of them suffered moderate surgical site infection while the third patient with comorbidities suffered severe surgical site infection. Antibiotic therapy and debridement with internal fixation retained were utilized during which microbiological culture were taken. The moderate infection patients got fully recovered after debridement and primary suture while the serious one had recurrence after the first debridement, and then the second operation was performed. SSI, however, relapsed after three days. Vacuum-assisted closure (VAC) system was placed in the third debridement. The severe patient got well recovered and discharged after displacement of VAC system. This report serves to explore a normal but overlooked factor for SSI. SSI is one of the most intractable complications after spine surgery and the report introduce some uncomplicated but effective methods to moderate and severe SSI. Sweat-contaminated is an inducement of SSI with Staphylococcus epidermidis that should attract surgeons' attention. For mild infection, changing dressing and infrared treatment can achieve good results. For moderate infection, one debridement and primary suture are enough. For severe infection, early application of VAC system can reduce the number of debridement and achieve good clinical outcome.


Manifest orientation: the theoretical link between the anatomy of the heart and the clinical electrocardiogram.
Einthoven related the apparent direction of the heart's electrical activity to the potential differences manifest in the limb leads and the axes of their orientation. From this beginning the linked concepts of heart vector and lead vector, equivalent dipole and lead field, complex heart source and complex volume conductor have continued the electrocardiographer's search for deeper insight into cardiac function from examination of the surface expression. However, this conceptual evolution has been uneven and has littered practical interpretation with diagnostic criteria that depend on assumptions of uneven validity. The good news is that some of the criteria are surprisingly helpful and that the shattering and reassembling of the conceptual framework relating the heart to the electrocardiogram may facilitate the construction of a more comprehensive and effective diagnostic approach.


Kinetics of regulation of neurotensin content in PC12 cells.
The mechanism by which nerve growth factor (NGF) and dexamethasone synergistically increase the content of neurotensin (NT) in PC12 cells can be partially separated into NGF and dexamethasone-mediated components by study of cultures pre-treated with either agent. The detectable early response of NGF-treated cells to dexamethasone is at least 24 hours faster than that of dexamethasone-treated cells to NGF, and is also greater in both absolute and relative magnitude. Both in NGF-treated cultures exposed to dexamethasone and in dexamethasone-treated cultures exposed to NGF, however, the rates of increase in NT content are initially low and then accelerate, suggesting periods of enzyme induction preceding NT accumulation. This suggestion is further supported by the absence of increases in the presence of actinomycin D, but an apparently paradoxical increase in NT content is observed in the presence of camptothecin. The findings are consistent with a complex interaction between NGF and dexamethasone, which might involve induction of multiple enzymes.


Impact of the biofilm mode of growth on the inner membrane phospholipid composition and lipid domains in Pseudomonas aeruginosa.
Many studies using genetic and proteomic approaches have revealed phenotypic differences between planktonic and sessile bacteria but the mechanisms of biofilm formation and the switch between the two growth modes are not well understood yet. In this study, we focused on inner membrane lipidome modifications when Pseudomonas aeruginosa cells were grown as biofilm. Lipid analyses were performed by Electrospray Ionization Mass Spectrometry. Results showed a drastic decrease of the uneven-numbered chain phospholipids and a slight increase of long chain PEs in sessile organisms as compared with planktonic counterparts, suggesting a better lipid stability in the bilayer and a decrease in membrane fluidity. The impact of sessile growth on lipid domains was then investigated by Brewster Angle Microscopy (BAM) and Atomic Force Microscopy (AFM). Observations showed that inner membrane lipids of P. aeruginosa formed domains when the pressure was close to physiological conditions and that these domains were larger for lipids extracted from biofilm bacteria. This is coherent with the mass spectrometry analyses.


[Bicyclic analogs of piperazine. XII. (1) - Synthesis of 3,8-diazabicyclo/3,2,1/octanes as potential antiparkinson agents].
As a part of research on 3,8-diazabicyclo [3,2,1] octanes, the Authors report on the synthesis of some amides of methyl, phenyl and cyclohexyltropic acid, potentially active as antiparkinson agents. Also reported is the synthesis of some compounds similar to two known drugs, Caramiphene and Cycrimine. These compounds differ from the said drugs in having a 3,8-diazabicyclo [3,2,1] octane as a basic moiety.


Intragenic Enhancers Attenuate Host Gene Expression.
Eukaryotic gene transcription is regulated at many steps, including RNA polymerase II (Pol II) recruitment, transcription initiation, promoter-proximal Pol II pause release, and transcription termination; however, mechanisms regulating transcription during productive elongation remain poorly understood. Enhancers, which activate gene transcription, themselves undergo Pol II-mediated transcription, but our understanding of enhancer transcription and enhancer RNAs (eRNAs) remains incomplete. Here we show that transcription at intragenic enhancers interferes with and attenuates host gene transcription during productive elongation. While the extent of attenuation correlates positively with nascent eRNA expression, the act of intragenic enhancer transcription alone, but not eRNAs, explains the attenuation. Through CRISPR/Cas9-mediated deletions, we demonstrate a physiological role for intragenic enhancer-mediated transcription attenuation in cell fate determination. We propose that intragenic enhancers not only enhance transcription of one or more genes from a distance but also fine-tune transcription of their host gene through transcription interference, facilitating differential utilization of the same regulatory element for disparate functions.


Structural Characterization of a Series of N5-Ligated MnIV -Oxo Species.
Analysis of extended X-ray absorption fine structure (EXAFS) data for the MnIV -oxo complexes [MnIV (O)(DMM N4py)]2+ , [MnIV (O)(2pyN2B)]2+ , and [MnIV (O)(2pyN2Q)]2+ (DMM N4py=N,N-bis(4-methoxy-3,5-dimethyl-2-pyridylmethyl)-N-bis(2-pyridyl)methylamine; 2pyN2B=(N-bis(1-methyl-2-benzimidazolyl)methyl-N-(bis-2-pyridylmethyl)amine, and 2pyN2Q=N,N-bis(2-pyridyl)-N,N-bis(2-quinolylmethyl)methanamine) afforded Mn=O and Mn-N bond lengths. The Mn=O distances for [MnIV (O)(DMM N4py)]2+ and [MnIV (O)(2pyN2B)]2+ are 1.72 and 1.70 Å, respectively. In contrast, the Mn=O distance for [MnIV (O)(2pyN2Q)]2+ was significantly longer (1.76 Å). We attribute this long distance to sample heterogeneity, which is reasonable given the reduced stability of [MnIV (O)(2pyN2Q)]2+ . The Mn=O distances for [MnIV (O)(DMM N4py)]2+ and [MnIV (O)(2pyN2B)]2+ could only be well-reproduced using DFT-derived models that included strong hydrogen-bonds between second-sphere solvent 2,2,2-trifluoroethanol molecules and the oxo ligand. These results suggest an important role for the 2,2,2-trifluoroethanol solvent in stabilizing MnIV -oxo adducts. The DFT methods were extended to investigate the structure of the putative [MnIV (O)(N4py)]2+ ⋅(HOTf)2 adduct. These computations suggest that a MnIV -hydroxo species is most consistent with the available experimental data.


Catheter ablation of right ventricular outflow tract tachycardia: value of defining coronary anatomy.
Thermal damage to coronary arteries during catheter ablation has been previously reported. Coronary artery damage during LV outflow tract ventricular tachycardia is well recognized. However, the relationship of the coronary arteries to the RV outflow tract during catheter ablation has not been delineated. The purpose of this study was to define the relationship between the RV outflow tract and the coronary arteries utilizing arteriography, echocardiography, CT angiography, and gross anatomic pathology. The relationship of the coronaries to the RV outflow tract was analyzed in three patients groups: Group 1: patients (n = 10) undergoing RV outflow tract ventricular tachycardia; Group 2: patients (n = 50) undergoing CT coronary angiography; Group 3: patients (n = 4) undergoing echocardiography during open heart surgery and intracardiac echocardiography (ICE) during catheter ablation of atrial fibrillation (n = 5). Group 1: The left main coronary artery was found to be 3.8 +/- 1.2 mm from the right ventricular outflow tract in patients undergoing ablation. Group 2: The minimum distance between the left main, left anterior descending, and right coronary artery to the RV outflow tract endocardial wall were 4.1 +/- 1.9 mm, 2.0 +/- 0.6 mm, and 4.3 +/- 1.9 mm (average +/- SD) respectively. Group 3: During open heart surgery using echocardiography, the minimum distance between the left main and the right coronary artery to the RV outflow tract were 3.4 +/- 0.35 mm and 2.0 +/- 0.1 mm, respectively. The distance between the let main coronary artery and the RVOT by ICE was 3.8 +/- 0.45 mm. The major coronary arteries lie in close proximity of the RVOT, and their anatomic course should be taken into consideration during ablation of ventricular tachycardias arising from the RV outflow tract.


Studies of fibrinogen metabolism in healthy and hypertensive female subjects with the use of autologous I-125-fibrinogen.
10 healthy female subjects and 15 female patients with essential hypertension were studied with respect to fibrinogen metabolism in a steady state. Autologous I-125-labeled fibrinogen (I-125-fibrinogen) was used as a tracer. Comparison of the results showed that plasma volume, t1/2 of plasma I-125-fibrinogen and fractional catabolic rate (j3p) of plasma fibrinogen (x) were not appreciably different in both groups of subjects, but plasma fibrinogen concentration, x and catabolic flux of x (j3px) (synthesis rate) were significantly higher in hypertensive subjects, whereas extravascular fibrinogen (y) and fractional transcapillary transferrate (j1) of x were significantly decreased in the patients. Further analyses of the data in both groups showed that there were significant correlations between diastolic blood pressure (P) and j1 with a regression equation of 41 = e-0.0285P, between x and j1 with a regression equation of x = 226e-0.939j 1 and between y and j1 with a regression equation of y = 12.6e0.624j 1. These results indicate that the observed decrease of j1 triggered the transition from normal to pathological steady state and is responsible for the altered metabolism and distribution of fibrinogen in hypertensive subjects.


[Eco-environmental effects and spatiotemporal evolution characteristics of land use change: A case study of Hexi Corridor, Northwest China.]
Based on the land use data of Hexi Corridor region from 1980 to 2020, we calculated the ecological environment quality index and analyzed the spatial and temporal evolution characteristics, change frequency, patterns, circles of the long time series land use type changes and its ecological environment quality, using the spatial analysis method of ArcGIS. The results showed that unused land was the main land use type in the study area during 1980-2020. The area of construction land, forest land, grassland, and water changed more, and the transition among land use types was obvious. The trends of deterioration and improvement of ecological environment quality in the study area occurred simultaneously and offset each other under certain conditions. The ecological environment quality index evolved in a 'U' shape, first decreasing and then increasing, with little change in overall ecological environment quality fluctuations. The spatial clustering of ecological quality was obvious, which was higher in the southeast and lower in the northwest, without high frequency and large change. The ecological quality in the southeast quadrant of the study area was the worst, followed by the southwest and northwest quadrants, while the ecological quality in the northeast quadrant was the best. The area of the continuously decline zone in ecological environment quality type conversion was larger than that of the continuously rising zone, indicating that ecological environmental protection in the Hexi Corridor had been effective during the study period. The hot spots of ecological quality change were mainly distributed in the central and southwestern part of the Hexi Corridor, and the cold spots were mainly distributed in the northwestern part.


Four-dimensional electron energy-loss spectroscopy.
Recent advances in scanning transmission electron microscopy have enabled atomic-scale focused, coherent, and monochromatic electron probes, achieving nanoscale spatial resolution, meV energy resolution, sufficient momentum resolution, and a wide energy detection range in electron energy-loss spectroscopy (EELS). A four-dimensional EELS (4D-EELS) dataset can be recorded with a slot aperture selecting the specific momentum direction in the diffraction plane and the beam scanning in two spatial dimensions. In this paper, the basic principle of the 4D-EELS technique and a few examples of its application are presented. In addition to parallelly acquired dispersion with energy down to a lattice vibration scale, it can map the real space variation of any EELS spectrum features with a specific momentum transfer and energy loss to study various locally inhomogeneous scattering processes. Furthermore, simple mathematical combinations associating the spectra at different momenta are feasible from the 4D dataset, e.g., the efficient acquisition of a reliable electron magnetic circular dichroism (EMCD) signal is demonstrated. This 4D-EELS technique provides new opportunities to probe the local dispersion and related physical properties at the nanoscale.


Antler-derived microRNA PC-5p-1090 inhibits HCC cell proliferation, migration, and invasion by targeting MARCKS, SMARCAD1, and SOX9.
The capability of microRNAs (miRNAs) to regulate gene expression across species has opened new avenues for miRNA-based therapeutics. Here, we investigated the potential of PC-5p-1090 (miR-PC-1090), a miRNA found in deer antlers, to control the malignant phenotypes of hepatocellular carcinoma (HCC) cells. Using Cell Counting Kit-8 and transwell assays, we found that heterologous expression of miR-PC-1090 inhibited HCC cell proliferation, migration, and invasion. Bioinformatics analysis indicated that predicted miR-PC-1090 targets, including MARCKS, SMARCAD1, and SOX9, were significantly elevated in HCC tissues, and their high expressions were associated with poor overall survival of HCC patients. Moreover, mechanistic investigations revealed that miR-PC-1090 promoted the degradation of MARCKS and SMARCAD1 mRNAs and hindered the translation of SOX9 mRNA by recognizing their 3' untranslated regions. Subsequent loss-of-function and rescue experiments confirmed the involvement of MARCKS, SMARCAD1, and SOX9 in miR-PC-1090-suppressed HCC cell proliferation, migration, and invasion. Notably, MARCKS knockdown induced the downregulation of phosphorylated MARCKS and a corresponding upregulation of phosphorylated AKT in HCC. Conversely, miR-PC-1090 repressed MARCKS phosphorylation and effectively circumvented the activation of the PI3K/AKT pathway. Furthermore, miR-PC-1090 regulates the Wnt/β-catenin pathway through SMARCAD1- and SOX9-mediated reduction of β-catenin expression. Overall, our results illustrate the tumor-suppressive activity and molecular mechanism of antler-derived miR-PC-1090 in HCC cells, indicating its potential as a multiple-target agent for HCC treatment.


Boundary formation in the hindbrain: Eph only it were simple...
Segmentation of the vertebrate hindbrain into rhombomeres is a key step in the development of a complex pattern of differentiated neurons from a homogeneous neuroepithelium. Many of the transcription factors important for establishing the segmental plan and assigning rhombomere identity are now known. However, the downstream effectors that bring about the formation of rhombomere boundaries are only just being characterized. Here we discuss molecules that could be responsible for segregating populations of cells from different rhombomeres. We focus on recent work demonstrating that the Eph family of receptor tyrosine kinases and their ligands, the ephrins, function in rhombomere-specific cell sorting and initiation of a structural boundary. We discuss the contributions of two mechanisms -- cell sorting and plasticity -- to the formation of rhombomere boundaries.


Immunomodulation in a treatment program including pre- and post-operative interleukin-2 and chemotherapy for childhood osteosarcoma.
The treatment applied in our Institution to children with localized osteosarcoma between 1991 and 1999 consisted of four interleukin 2 (IL-2) courses (9 x 10(6) IU/mL/daily x 4), alternated with pre- and post-operative polichemotherapy. The aims of the present study were to quantify the modifications of some immunological parameters induced by IL-2 and to verify whether polychemotherapy could reduce them. An additional aim was to assess whether any correlation between the immune modifications and the clinical outcome could be found. We evaluated in 18 consecutive patients the following changes, induced in blood by each IL-2 course: number of lymphocyte subpopulations and natural killer (NK) cells, lymphokine activated killer (LAK) and NK activities. Chemotherapy did not influence the modifications of the number of NK and CD4+ cells and of the LAK and NK activities, induced by each of the four courses of IL-2. The magnitudo of the NK activity and the peak of the NK absolute counts significantly correlated with the clinical outcome. The results show that the use of IL-2 permitted a repeated immune activation despite the intensive chemotherapy. Furthermore, although the limited number of cases precludes any definitive conclusion, the results suggest a possible role of the NK cells in the control of osteosarcoma.


[Dynamic immunological and cytochemical markers in the induced differentiation of the K-562 cell line].
The possibility of TPA-induced differentiation of K-562 cell line was studied. Monoclonal antibodies against differentiating antigens of HAE erythroid lineage and against myelomonocytic ICO lineage raised in the USSR Cancer Research Centre were used. Changes in immunological and cytochemical indexes suggest that K-562 cell differentiation goes in the erythroid direction. The cells lost early differentiation and acquired late differentiation markers.


A prospective study of bowel preparation for colonoscopy with polyethylene glycol-electrolyte solution versus sodium phosphate in Lynch syndrome: a randomized trial.
Lynch gene carriers undergo regular surveillance colonoscopies. Polyethylene glycol-electrolyte solution (PEG) is routinely prescribed for bowel cleansing, but often poorly tolerated by patients. Sodium phosphate (NaP) may be an alternative. Prospective and random comparison of bowel preparation with PEG and NaP on colon cleansing and patients' acceptance. Patients, who previously underwent a colonoscopy, were invited to participate and randomly assigned to either PEG or NaP. They were asked to fill in a questionnaire about preparation tolerability and future preferences. The endoscopist filled out a report about the quality of colon cleansing. 125 Patients were included in the study. Nine (7%) were excluded because of missing data. The remaining 116 patients (53 PEG and 63 NaP) were included in the analysis. Baseline characteristics did not differ between groups. Before colonoscopy 20 (38%) patients using PEG experienced the preparation almost intolerable, in contrast to 7(11%) of those using NaP (P = 0.001). Eleven patients in the PEG group and 48 in the NaP group would prefer NaP in the future. The colonoscopy was poorly tolerated in 17% of the individuals in both groups (P = 0.963). The endoscopist observed a more than 75% clean colon in 83% of patients on PEG and in 71% of patients on NaP (P = 0.076), however the coecum (P = 0.025) and ascending colon was cleaner after PEG. Lynch patients tolerated NaP better and preferred this formula for future bowel preparation. Colon cleansing was suboptimal with both treatments with a tendency towards a cleaner proximal colon with PEG.


Diminution by captopril of the diuretic, natriuretic and kallikrein stimulating action of furosemide by reduction in its renal secretion.
The effect of furosemide (40 mg iv) on diuresis, natriuresis and renal kallikrein and kinin excretion was investigated without and with pretreatment by captopril (100 mg po). Furosemide stimulated markedly diuresis and natriuresis as well as urinary kallikrein and kinin excretion. Pretreatment by captopril (C) reduced the diuretic and natriuretic effect of furosemide significantly (UNaV pre-C: +15, 1 +/- 2.1 ml/min vs. post-C: 7.0 +/- 0.3 ml/min; p less than 0.001). Similar changes in urinary kallikrein and kinin excretion were observed after captopril pretreatment, but because of the great coefficient of variation these changes did not reach statistical significance. The reason for the reduced activity of furosemide after captopril pretreatment was the diminished proximal-tubular secretion of furosemide, as it could be shown by direct measurement of the drug in urine. After furosemide injection changes in plasma aldosterone concentration paralleled changes in renal kallikrein and kinin excretion. However, after captopril there was a sharp dissociation between aldosterone, which was diminished by captopril continuously, and renal kallikrein and kinins, which were still stimulated by furosemide. These results suggest that renal kallikrein-kinin system is stimulated by furosemide directly and independently of aldosterone secretion.


Biogenesis, assembly and trafficking of acetylcholinesterase.
Acetylcholinesterase (AChE) is expressed as several homomeric and heterooligomeric forms in a wide variety of tissues such as neurons in the central and peripheral nervous systems and their targets including skeletal muscle, endocrine and exocrine glands. In addition, glycolipid-anchored forms are expressed in erythropoietic and lymphopoietic cells. While transcriptional and post-transcriptional regulation is important for determining which AChE oligomeric forms are expressed in a given tissue, translational and post-translational regulatory mechanisms at the level of protein folding, assembly and sorting play equally important roles in assuring that the AChE molecules reach their intended sites on the cell surface in the appropriate numbers. This brief review will focus on the latter events in the cell with the goal of providing novel therapeutic interventional strategies for the treatment of organophosphate and carbamate pesticide and nerve agent exposure. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms.


Burden of care and coping strategies among informal caregivers of people with behavioral and psychological symptoms of dementia in rural south-western Uganda.
Caregiving is a draining role that inflicts a significant level of burden upon caregivers for older people with Behavioral and Psychological Symptoms of Dementia (BPSD). Caregiver burden is associated with poor health outcomes for both the people with BPSD and their caregivers. This study explored the burden of care and coping strategies used by informal caregivers of older people with BPSD in rural Southwestern Uganda. This was a qualitative study among informal caregivers of older people with BPSD in Rubanda and Rukiga districts. We conducted in-depth interviews with a purposive sample of 27 caregivers using an interview guide. The interviews were conducted in the local language, audio recorded, transcribed, translated into English, and thematically analyzed. There were two major themes: caregiver burden and coping strategies. Caregiver burden was described as financial, physical, psychological and social. Caregivers mainly used emotion-focused coping strategies (religious coping, acceptance and emotional support seeking). Problem-focused coping strategies (planning) and dysfunctional coping strategies (self-distraction) were used to a lesser extent. Informal caregivers of people with BPSD adopted both emotional and problem-focused coping strategies to cope with the burden of care for people with BPSD. Such coping strategies seemed to lighten the burden of caring, in the long motivating the caregivers to continue with the caring role.


Neighbourhood quality and self-rated health: a survey of eight suburban neighbourhoods in the Vancouver Census Metropolitan Area.
We investigated the relationship between perceptions of neighbourhood quality and self-rated health for residents of eight suburban neighbourhoods with modestly contrasting income profiles in the Vancouver Census Metropolitan Area. Survey respondents from lower income neighbourhoods more often rated their health as fair/poor, and perceived their neighbourhood to be of poor quality. The strongest predictors for fair/poor health status were employment status, body mass index, neighbourhood satisfaction, and age, while modest predictors were annual household income, neighbourhood median income profile, and perceptions of neighbourhood safety. The unique contribution of this study is its demonstration that social gradients in self-rated health are observable between neighbourhoods of even modestly contrasting income profiles.


Laparoscopic distal pancreatectomy with preservation of the spleen and splenic vessels for benign pancreas neoplasm.
Laparoscopic distal pancreatectomy to conserve the spleen is a beneficial operation for patients with benign and borderline malignancy in the pancreas. With this procedure, it is very desirable to preserve the splenic artery and vein as well. From May 2000 to July 2003, five laparoscopic distal pancreatectomies with preservation of the spleen and splenic vessels were performed for benign pancreas neoplasm at Ewha Womans University Mokdong Hospital in Seoul, Korea. The postoperative pathologic diagnoses were two serous cystadenomas, two mucinous cystadenomas, and one solid and papillary epithelial tumor. The tumors ranged in size from 1.5 to 7 cm. Four trocars (10-15 mm) and a laparoscopic linear stapler were used for transection of the pancreas. The mean operation time was 348 min, and the mean length of the incision for extraction was 3.6 cm. The mean postoperative hospital stay was 10.4 days. There was no complication or mortality. Laparoscopic distal pancreatectomy with preservation of the spleen and splenic vessels is a relatively safe and feasible option for the management of benign tumor or borderline malignancy in the distal pancreas.


Gastroesophageal Balloon Tamponade Simulation Training with 3D Printed Model Improves Knowledge, Skill, and Confidence.
Gastroesophageal balloon tamponade (BT) tube placement is a life-saving procedure for refractory bleeding from gastroesophageal varices performed by gastroenterologists, intensivists, internists, and emergency medicine physicians. Despite a recognized need for procedural training, no standard curriculum or assessment tools exist. Given the infrequent performance of this procedure, the development of a representative and accessible simulation model would permit hands-on training to practice and maintain proficiency with BT tube placement. To assess BT tube placement performance before and after a novel simulation-based learning module in gastroenterology fellows and faculty. A 16-item knowledge questionnaire and 22-item procedural skill checklist utilizing a novel 3D printed esophagus model were developed to assess participant knowledge, procedural skills, and confidence prior to our simulation-based intervention and again 8-12 weeks after. Performance metrics were compared pre- and post-intervention within groups and between participant groups. Fifteen gastroenterology fellows (of 15 eligible; 100%) and 14 gastroenterology faculty (of 29 eligible; 48%) completed training. Fellows demonstrated improvement in knowledge (55% to 79%, p < 0.001) and procedural skill (35% to 57%, p < 0.001) following training. Baseline faculty performance did not differ from fellows' performance and post-intervention showed similar improvement in knowledge (61% to 77%, p = 0.001) and procedural skill (40% to 49%, p = 0.147). Overall satisfaction with training was high in both groups post-intervention and faculty felt more confident teaching fellows. The presented learning module offers a unique, low stakes opportunity for learners to improve skills, gain knowledge, and build confidence in placing BT tubes using a realistic simulation model.


[The action of potassium orotate in prophylactic and therapeutic administration to irradiated rats].
A study was made of the radioprotective and therapeutic effect of potassium orotate on rats subjected to whole-body gamma-irradiated with doses of 11, 9 and 4 Gy. The preparation exerted a radioprotective action when administered intraperitoneally 60 min before irradiation as was estimated with a reference to the survival rate and leukocyte level in the peripheral blood. Fron the analysis of the peripheral blood consumption it was inferred that potassium orotate weakened the radiation damage and enhanced the recovery processes during the postirradiation period.


CA19-9 is a significant prognostic marker of patients with stage III gastric cancer.
Due to prognostic heterogeneity within a stage of gastric cancer (GC), identification of patients with a high risk for recurrence after resection is important. We aimed to identify the prognostic significance of preoperative serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) levels in patients with Stage I, II, and III GC who underwent R0 gastrectomy. A total of 794 patients were included in this study after excluding 72 patients with CA19-9 <1.0 U/mL. Receiver operating characteristic curves were drawn to assess the optimal cut-off values of CEA and CA19-9 for disease recurrence. The optimal cut-off values of CEA and CA19-9 levels were 2.9 ng/mL and 46.3 U/mL, respectively. Multivariate analysis for relapse-free survival (RFS) showed that stage of GC, CA19-9 levels, postoperative adjuvant chemotherapy, and venous invasion were significant independent factors. The RFS and overall survival (OS) of patients with CA19-9 ≥ 46.3 U/mL were significantly lower than those with CA19-9 < 46.3 U/mL in Stage III GC. However, the RFS of GC patients with CA19-9 ≥ 463 U/mL tended to be better than those with CA19-9 levels between 46.3 and 463 U/mL. The RFS and OS of patients with CA19-9 ≥ 46.3 U/mL were significantly lower than those with CA19-9 < 46.3 U/mL in Stage III GC. However, there was no value dependency of extremely elevated CA19-9 on RFS. Further risk stratification can be obtained by measuring preoperative serum CA19-9 in stage III GC.


Common fractures of the extremities. How to recognize and treat them.
Primary care physicians are called on to see and treat a variety of orthopedic problems, including the common fractures discussed in this article. They must recognize the fractures they feel comfortable in treating and differentiate those that should be referred to someone with more experience in complex fracture care. The goal of treatment is to restore optimal function without deformity.


Identification of Survival-Related Metabolic Genes and a Novel Gene Signature Predicting the Overall Survival for Patients with Uveal Melanoma.
Uveal melanoma (UM) is the most common primary intraocular malignancy among adults. Altered metabolism has been shown to contribute to the development of cancer closely, but the prognostic role of metabolism in UM remains to be explored. This study aimed to construct a metabolic-related signature for UM. We collected the mRNA sequencing data and corresponding clinical information from The Cancer Genome Atlas and Gene Expression Omnibus databases. A univariate Cox regression analysis, the Lasso-penalized Cox regression analysis, and multivariate Cox regression analyses were used to construct a metabolic signature based on TCGA. The time-dependent ROC and Kaplan-Meier survival curves were calculated to validate the prognostic ability of the signature. The immune-related features and mutation profile were characterized by CIBERSORT and maftools between high- and low-risk groups. A novel metabolic-related signature (risk score = -0.246*SLC25A38 - 0.50186*ABCA12 + 0.032*CA12 + 0.086*SYNJ2) was constructed to predict the prognosis of UM patients. In TCGA and GSE22138, the signature had high sensitivity and specificity in predicting the prognosis of UM patients (survival probability; p < 0.0001, p = 0.012) . Gene Ontology pathway enrichment analysis and GSEA were used to discriminate several significantly enriched metabolism-related pathways, including channel activity and passive transmembrane transporter activity, which may reveal the underlying mechanisms. The high-risk group had more immune cell infiltration and greater distribution of BAP1 mutations. Our study developed a robust metabolic-gene signature based on TCGA to predict the prognosis of UM patients. The signature indicates a dysregulated metabolic microenvironment and provides new metabolic biomarkers and therapeutic targets for UM patients.


The relative importance of internal and external physical resistances to mass transfer for caffeine release from apple pectin tablets.
The relative importance of the physical resistances to mass transfer have been explored by using halved 13 mm diameter apple-pectin tablets containing caffeine, in different external stirring environments within a beaker containing simulated gastric fluid. The effects of different external (outside of the tablets) mass-transfer resistances to the tablets created through two different stirrer types and stirrer speeds, and different internal (inside of the tablets) mass-transfer resistances created through different tablet concentrations and thicknesses, have been studied. These studies enable internal diffusion coefficients of caffeine through the apple pectin matrix to be estimated, as well as estimating the external mass-transfer coefficients from benzoic acid dissolution, which are in the range of 6.5 × 10-6 m/s - 2.4 × 10-5 m/s for the 0.6 mm thick tablets and 4.0 × 10-6 m/s - 1.6 × 10-5 m/s for the 7 mm thick tablets. The diffusion coefficients for different caffeine concentrations in the apple pectin half-tablets have also been calculated in this study. The diffusivity of caffeine in the 7 mm half-tablets with 1% caffeine through 99% pectin was around (1.8 ± 0.5) × 10-10 m2/s. This study points towards the development of multifilm mass-transfer theory for food digestion to create a more fundamentally based understanding of in-vitro digestion systems as an addition to the use of realistic in-vitro food digestion apparatus and give a better correlation between in-vitro and in-vivo digestion tests.


Endoscopic Discectomy of Rostrally and Caudally Migrated Lumbar Disc Herniations; A Technique Video.
Surgical treatment of extremely migrated caudal and rostral lumbar disc herniations is technically challenging. Traditional open technique often requires more bone resection which can lead to rare but significant complications such as pars fracture or instability requiring fusion surgery. Endoscopic discectomy is a safe alternative to traditional open surgery with acceptable complication rates.1-4 Endoscopic discectomy provides the advantage of excellent visualization and maneuverability while minimizing soft tissue trauma and bony resection which can result in less postoperative pain, opioid consumption, and quicker recovery.5 We present a surgical technique guide for endoscopic discectomy of two patients with very high rostral (grade 1) and caudal (grade 6) lumbar disc herniations as graded by Ahn's modification of the Lee-Kim grading classification.6,7 Risks, benefits and alternatives to surgery discussed with patients and the patients consented to the procedure. This video is not a replacement to hands on training.


A randomized trial comparing Arglaes (a transparent dressing containing silver ions) to Tegaderm (a transparent polyurethane dressing) for dressing peripheral arterial catheters and central vascular catheters.
The purpose of this trial was to prepare for a large randomized trial comparing Arglaes film dressing, a recent innovation containing silver ions, against Tegaderm, a transparent polyurethane dressing. Thirty-one patients admitted to the intensive care unit and requiring the insertion of an arterial line or central venous catheter were recruited into the study. Skin swabs were taken from the insertion sites prior to catheterization and on removal of the intravascular device to measure skin colonization rate between the two dressings. The catheter tips were also cultured on removal to establish if there was a difference between the two groups. No statistical differences were found in bacterial growth between the two dressings.


Sensitive and accurate detection of ALP activity using a fluorescence on-off-on switch and mass barcode signal amplification.
Alkaline phosphatase (ALP) is an important biomarker for many diseases. Therefore, the sensitive and accurate detection of ALP activity is essential for fundamental biochemical processes and clinic diagnosis. Herein, we design a fluorescent on-off-on switch for sensitive and visual detection of ALP activity. Meanwhile, mass barcode-modified quantum dots (QDs) amplified the LC-MS/MS detection signal in complex biological samples. Firstly, the QDs were modified with phosphorylated Gly-Gly-Phe-Phe-Tyr (OPO3H2) peptide (GGFFYp) and the mass barcode. The fluorescence of QDs-SS-Yp was quenched by fluorescence resonance energy transfer (FRET) between QDs-SS-Yp and dansyl chloride (DNS). ALP can hydrolyze the phosphorylated peptide to form peptide self-assemblies on the QDs-SS-Yp surfaces. The effective separation distance between the QDs-SS-Yp donor and DNS acceptor becomes larger, restricting FRET between the QDs-SS-Yp and DNS. At this point, the obvious QDs-SS-Yp fluorescence signal can be restored. However, the absence of ALP results in no peptide self-assembly on the QDs-SS-Yp surface and no obvious QDs-SS-Yp fluorescence signal was detected. Therefore, the ALP activity can be analyzed according to the degree of fluorescence restoration by the fluorescence on-off-on switch. Finally, the small tag molecules obtained by cleaving the disulfide bond of the QDs-SS-Yp as a mass barcode were used to amplify the LC-MS/MS detection signal. The proposed approach shows a good linear relationship (from 0.01 to 2.4 U L-1) and has the significant advantage of a low detection limit of 0.001 U L-1.


Fusion of HIV-1 envelope-expressing cells to human glomerular endothelial cells through an CXCR4-mediated mechanism.
A central question in the pathogenesis of HIV-associated thrombotic microangiopathic (HIV-TMA) lesions is whether the HIV-1 envelope glycoprotein (HIV-1 Env) can interact directly with human glomerular endothelial cells (HGECs) through specific HIV-1 co-receptors. The goal of this study was to determine whether cultured primary HGECs express significant levels of the major HIV-1 co-receptors CD4, CXCR4, and/or CCR5 to allow fusion interactions with HIV-1. The expression of CD4, CXCR-4 and CCR-5 was assessed in cultured HGECs by reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry using specific antibodies. The HIV-1 Env-mediated membrane fusion of target glomerular cells was evaluated by a fluorescent dye transfer-based cell-cell fusion microscopic method. HGECs express CXCR4 mRNA and protein as determined by RT-PCR and immunostaining with phycoerythrin-conjugated anti-CXCR4 Mab 12G5. CD4 and CCR5 were not detected in HGECs, either by RT-PCR or by surface immunostaining with specific antibodies. Incubation of HGECs with cells expressing a CD4-independent envelope strain (HIV-1IIIB-8x) and the CD4-dependent envelope strain (HIV-1IIIB) resulted in transfer of fluorescent dyes of approximately 20% after 8-16 h incubation at 37 degrees C. Incubation in the presence of inhibitors (C34, which blocks six-helix bundle formation, and AMD3100, which interacts with CXCR4) reduced dye transfer by 60%-80%, confirming that the dye transfer was specific with respect to gp120-gp41-mediated fusion. Cultured primary HGECs express CXCR4 but not CD4 or CCR5. The ability of HGECs to promote fusion by a CD4-independent HIV-1 envelope glycoprotein suggests that these cells may become a potential direct target of certain HIV-1 isolates.


Collateral compensation of severe carotid stenosis.
In 516 patients who had endarterectomies for unilateral severe carotid stenoses, arteriography demonstrated no contralateral severe stenoses or occlusions. Pre and postoperative ocular pneumoplethysmography (OPG-Gee) measured simultaneous bilateral ophthalmic systolic pressures (OSP). Immediately after each OPG test a brachial systolic pressure (BSP) was measured with a stethoscope, cuff and manometer. Bilateral ophthalmobrachial systolic pressure (OBSP) indices were calculated from the three pressures measured with the combined testing. Analysis of these OBSP data indicates that the severe stenoses were relatively well compensated in 314 of the 516 patients (61%) whereas there was limited collateral compensation in the remaining 202 patients (39%). The data also suggest that the latter group incurs a greater element of compensatory central hypertension, which is reversed by carotid endarterectomy.


The role of prostate-specific antigen in light of new scientific evidence.
Review the scientific evidence acquired in recent years on Prostate-Specific Antigen (PSA). Analysis of the available evidence on the current role of PSA, according to a panel of experts who recorded their experience on the subject. Currently, PSA cannot be considered solely an indicator of the presence or absence of prostate cancer. Rather, the determination of PSA assists the urologist in indicating the most appropriate treatment for a patient with benign prostatic hypertrophic (BPH), as well as in suspecting a prostatic tumour when the PSA reading increases >0,3 ng/ml, in patients treated with 5-alpha-reductase inhibitor, over the reading achieved at six months of having initiated this treatment. Moreover, PSA is a key factor in the follow-up of patients with prostate adenocarcinoma who undergo surgery, radiation therapy or minimally invasive techniques. PSA helps to define biochemical recurrence, suggest the existence of a local or distal recurrence and propose or rule out adjuvant therapies. New data on the current role of PSA in the management of patients treated for BPH and/or prostate cancer should be taken into account.


Knocking-in the R142C mutation in transglutaminase 1 disrupts the stratum corneum barrier and postnatal survival of mice.
Mutations in the gene encoding transglutaminase 1 (TG1) are responsible for various types of autosomal recessive congenital ichthyosis (ARCI), such as lamellar ichthyosis (LI), congenital ichthyosiform erythroderma (CIE) and some minor variants of ARCI. A point mutation of R143C in the β-sandwich domain of TG1 has been often identified in patients with LI or CIE. To elucidate the effect of that point mutation on skin barrier structures and functions, we generated mice with a point mutation of R142C, which corresponds to the R143C mutation in human TG1. A mouse line with the R142C point mutation in TG1 was established using a gene targeting technique and the Cre-loxP system. The skin phenotypes were analyzed in homozygous mutant Tgm1(R142C/R142C) mice. In the skin of Tgm1(R142C/R142C) mice, expression of the mutant transcripts was comparable with wild-type or Tgm1(+/R142C) mice. However, the amount of mutated protein in the skin was markedly decreased in Tgm1(R142C/R142C) mice, and the TG1 activity of Tgm1(R142C/R142C) keratinocytes was almost lost. Tgm1(R142C/R142C) mice exhibited morphological and functional skin barrier defects and neonatal lethality. The stratum corneum of those mice lacked cornified envelopes, and loricrin, the major structural component, failed to assemble at the corneocyte cell periphery. Tgm1(R142C/R142C) mice showed a marked increase in transepidermal water loss and their skin was easily permeable to toluidine blue dye. The intercellular lipid lamellar structures of the stratum corneum were irregular and the 13-nm periodic X-ray diffractions from the stratum corneum lipid molecules were lost in vivo. From these results, we suggest that the R142C mutation of TG1 reduces the enzyme stability which is indispensable for development of the stratum corneum and skin barrier function and for postnatal survival of mice.


Simultaneous identification and quantification of nitro-containing explosives by advanced chemometric data treatment of cyclic voltammetry at screen-printed electrodes.
The simultaneous determination of three nitro-containing compounds found in the majority of explosive mixtures, namely hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), 2,4,6-trinitrotoluene (TNT) and pentaerythritol tetranitrate (PETN), is demonstrated using both qualitative and quantitative approaches involving the coupling of electrochemical measurements and advanced chemometric data processing. Voltammetric responses were obtained from a single bare screen-printed carbon electrode (SPCE), which exhibited marked mix-responses towards the compounds examined. The responses obtained were then preprocessed employing discrete wavelet transform (DWT) and the resulting coefficients were input to an artificial neural network (ANN) model. Subsequently, meaningful data was extracted from the complex voltammetric readings, achieving either the correct discrimination of the different commercial mixtures (100% of accuracy, sensitivity and specificity) or the individual quantification of each of the compounds under study (total NRMSE of 0.162 for the external test subset).


Draft Genome Sequence of Tenacibaculum ovolyticum To-7Br, Recovered from a Farmed Atlantic Salmon (Salmo salar).
We present the draft genome sequence of Tenacibaculum ovolyticum isolate To-7Br, recovered from a gill of a farmed specimen of Atlantic salmon (Salmo salar) showing signs of tenacibaculosis. This study provides the first detailed insights into the genomic characteristics of T. ovolyticum isolated for the first time from fish farmed in Chile.


A case of chronic demyelinating polyneuropathy resembling the Guillain-Barré syndrome.
A case of demyelinating polyneuropathy is reported which was clinically and pathologically indistinguishable from the Guillain-Barré syndrome, with the exception that the symptoms progressed steadily for 7 months. Pathologically, the peripheral nerves and intraspinal roots showed selective demyelination with axonal sparing and patchy mononuclear inflammation. The posterior columns of the spinal cord also showed selective demyelination with axonal sparing. The simultaneous destruction of central and peripheral myelin is discussed in relation to the immune theory for the Guillain-Barré syndrome. Numerous anterior horn cells showed severe chromatolysis although there was little axon loss. It is suggested that chromatolysis may occur after severe and longstanding demyelination.


Neighborhood Socioeconomic Disadvantage Associated With Increased 90-Day Mortality Following Radical Cystectomy.
To examine relationships between neighborhood socioeconomic disadvantage and outcomes following radical cystectomy (RC). A retrospective single institution study of consecutive RCs performed for bladder cancer between 2011 and 2019. Major complications, mortality and survival outcomes were compared using Cochran-Armitage or Kruskal-Wallis tests. Cox proportional hazards models were used for time-to-event analyses. A total of 906 patients were included in analysis. Overall 90-day mortality was 2.98% (27/906). Ninety-day mortality rates observed in the least (first) and most (fourth) disadvantaged ADI quartiles were 0% (0/115) and 6.5% (12/185), respectively. Patients from the fourth quartile demonstrated worse overall survival and recurrence free survival than those in the first quartile. ADI quartile was positively associated with muscle invasive (P = .0006) and node positive (P = .042) disease. ADI percentile was an independent predictor for 90-day mortality (adjusted OR: 1.022, CI: 1.004-1.04, P = .015). Higher rates of mortality and worse oncologic outcomes were observed for patients residing in the most disadvantaged quartile. ADI was associated with higher likelihood of 90-day mortality and may therefore be useful in patient counseling, risk stratification, and post-discharge management.


Establishment of an induced pluripotent stem cell line (ZZUSAHi002-A) derived from peripheral blood mononuclear cells of a healthy individual.
Peripheral blood mononuclear cells (PBMCs) were isolated from a 32-year-old female and were reprogrammed to human induced pluripotent stem cells (iPSCs) using non-integrative Sendai viral vectors containing reprogramming factors OCT4, SOX2, KLF4 and cMYC. The ZZUSAHi002-A iPSC line expresses pluripotency markers, exhibits a normal female karyotype (46, XX) and has the capacity to differentiate into three germ layers in vivo. This iPSC line may be used for cell transplantations, drug testing and biological tissue engineering.


Bakuchiol analogs inhibit monoamine transporters and regulate monoaminergic functions.
Monoamine transporters play key roles in controlling monoamine levels and modulating monoamine reuptake. The objective of the present study was to identify monoamine transporter inhibitors from herbal sources. We discovered that bakuchiol analogs isolated from Fructus Psoraleae inhibited monoamine transporter uptake to differing degrees. The bakuchiol analog, Delta3,2-hydroxybakuchiol was the most potent and efficacious reuptake blocker and was thus selected as the candidate target. Monoamine transporter inhibition by Delta3,2-hydroxybakuchiol was more selective for the dopamine transporter (DAT) (IC50=0.58+/-0.1 microM) and norepinephrine transporter (NET) (IC50=0.69+/-0.12 microM) than for the serotonin transporter (SERT) (IC50=312.02+/-56.69 microM). Delta3,2-Hydroxybakuchiol exhibited greater potency (pEC50 for DAT and NET) than bupropion and exhibited similar efficacy (E(max) for DAT and/or NET) to bupropion and GBR12,935. Pharmacokinetically, Delta3,2-hydroxybakuchiol competitively inhibited DAT and NET with partial reversibility and occupied cocaine binding sites. Moreover, Delta3,2-hydroxybakuchiol counteracted 1-methyl-4-phenylpyridinium-induced toxicity in cells expressing DAT with similar efficacy to GBR12,935. In vivo studies showed that Delta3,2-hydroxybakuchiol increased the activity of intact mice and improved the decreased activity of reserpinized mice. In the conditioned place preference test, preference scores in intact mice were unaffected by Delta3,2-hydroxybakuchiol treatment. Bakuchiol analogs, especially Delta3,2-hydroxybakuchiol, are monoamine transporter inhibitors involved in regulating dopaminergic and noradrenergic neurotransmission and may have represented potential pharmacotherapies for disorders such as Parkinson's disease, depression, and cocaine addiction.


Cooperatively Catalyzed Activation of Thioglycosides That Bypasses Intermediacy of Glycosyl Halides.
Reported herein is the development of a novel method for activating thioglycosides without a glycosyl halide intermediate. This has been achieved through the use of a silver salt coupled with an acid additive and molecular iodine. The enhanced stereocontrol was achieved via the H-bond mediated aglycone delivery (HAD) method, and the extended trisaccharide synthesis was achieved via iteration of deprotection and glycosylation steps.


Adolescents' attitudes toward non-suicidal self-injury (NSSI) and their perspectives of barriers to seeking professional treatment for NSSI.
This study aimed to investigate the attitudes of adolescents toward NSSI, and to explore their perspectives on barriers to seeking professional treatment for NSSI. A qualitative phenomenological design was used to conduct in-depth interviews with 17 adolescents with NSSI in a psychiatric hospital in Beijing, China. Data from the 17 adolescents were analyzed using Colaizzi's 7-step analysis. Two themes were extracted: (1) attitudes toward NSSI (normal, effective, ignorant, disgraceful); (2) subjective/objective barriers to seeking professional treatment (negative attitudes toward NSSI, fear of being regarded as an attention getter, fear of interfering with personal relationships, fear of aggravating the family burden, fear of being criticized by parents, fear of ongoing hospitalization, fear of the side effects of medication, etc.). It is suggested to strengthen the knowledge of NSSI among adolescents, families and society, formulate interventions suitable for Chinese sociocultural backgrounds, and cultivate the specialty literacy of mental health nurses and their abilities to identify the barriers, which are required for eliminating barriers to seeking professional treatment and establishing a system for seeking full coverage of professional treatment.


Loss of o-phthaldialdehyde reactivity during storage of infant cereals.
A fluorimetric method was used to determine the o-phthaldialdehyde (OPA) reactivity of amino groups for the assessment of non-enzymatic browning reactions in products with a prolonged shelf-life. The studies were conducted in four commercial infant cereals: wheat-based '7-cereals' and '8-cereals', and gluten-free 'rice cereal' and 'rice-corn cereal'. The cereals were monitored at 28 degrees C for 4 or 16 weeks, or under high water activity (0.65) conditions at 25 degrees C or 55 degrees C for 1, 2, 3 or 4 weeks. OPA reactivity gradually decreased during storage under all temperature, time and water activity conditions, with especially marked losses under conditions of greatest heat intensity and high water activity. According to the present results, the determination of OPA reactivity offers a simple, rapid and reliable method to evaluate non-enzymatic browning.


Shallow Quaternary groundwater in the Lake Chad basin is resilient to climate change but requires sustainable management strategy: Results of isotopic investigation.
Within the Lake Chad Basin, the unconfined Quaternary aquifer offers permanent and easy access to water resources. This transboundary regional aquifer is shared by Chad, Niger, Nigeria and Cameroon and extends over ~500,000 km2. Climatic conditions and repeated droughts as well as the intensification of agriculture in the region have multiple negative impacts on the aquifer such as changes in groundwater level and its quality. Being a strategic water resource for the whole Chadian region, the groundwater potential of the Quaternary aquifer must be better characterized and understood to evaluate its resilience to climate change and anthropogenic impact. Stable isotopes and tritium of the water molecule were used to estimate water origin and residence time at the regional scale and to elucidate the interconnections between the different hydrological and hydrogeological components. Results show active recharge processes to the Quaternary aquifer as well as dynamic connections with surface waters (both river courses and wetlands) but also indicate less dynamic behavior of the Quaternary groundwater resource in some areas of the region. Based on the isotopic investigations, the Quaternary aquifer in the Chad basin was found to be resilient to climate change but its hydrogeological specificities (dependence to surface water from the upstream basins and transboundary nature of its structure) can make it prone to inadequate management strategies.


Disparity between Yersinia pestis and Yersinia enterocolitica O:8 in YopJ/YopP-dependent functions.
YopP in Y. enterocolitica and YopJ in Y. pseudotuberculosis, have been shown to exert a variety of adverse effects on cell signaling leading to suppression of cytokine expression and induction of programmed cell death. A comparative in vitro study with Y. pestis and Y. enterocolitica O:8 virulent strains shows some critical disparity in YopJ/YopP-related effects on immune cells. Involvement of yopJ in virulence was evaluated in mouse model of bubonic plague.


Outcome of Irrigation and Debridement With Topical Antibiotics Delivery for the Management of Periprosthetic Joint Infection Occurring Within 3 Months Since the Primary Total Joint Arthroplasty.
Irrigation and debridement with modular component exchange is appealing for surgeons to treat early-stage periprosthetic joint infection (PJI). However, the indication, perioperative protocol, and success rate remain controversial. This study is the first one to present results of debridement, antibiotics, and implant retention (DAIR) with integrated MIT (modular component exchange, povidone-iodine and topical antibiotics delivery) protocol for treating PJI occurring within 3 months since the primary total joint arthroplasty. We retrospectively analyzed patients who received DAIR with MIT protocol in our department between January 2011 and May 2018. Topical antibiotics were delivered in all cases. Topical antibiotics infusion was applied for those infected with multidrug-resistant bacteria, fungus, polymicrobial infection, and culture negative one. Failure was defined as additional surgical intervention for infection after DAIR; persistent sinus tract, drainage or excessive joint pain; need for suppressive antibiotics therapy due to the infection; infection relapse with the same pathogen; reinfection with different microorganism; and infection-related death. A total of 73 patients with a mean age of 63.30 ± 10.97 years were included in this study, including 43 men and 30 women. There are 41 knees and 32 hips. Thirty patients had sinus tract. With a mean follow-up of 63.79 ± 18.57 months, there were 9 failures in total with an overall success rate of 87.67%. The success rate was 88.57% and 86.84% for those receiving topical antibiotics infusion postoperatively and those without. DAIR with a standard MIT protocol is a viable and safe option for PJI occurring within 3 months since the primary total joint arthroplasty. Level 4, therapeutic study.


First Record and Distribution of Ganaspis brasiliensis (Hymenoptera: Figitidae: Eucoilinae), a Parasitoid of Drosophila suzukii (Diptera: Drosophilidae) in Argentina.
The eucoiline species Ganaspis brasiliensis (von Ihering) (Hymenoptera: Figitidae) is recorded for the first time in Argentina, with confirmation of parasitism of Drosophila suzukii (Matsumura) infesting healthy raspberry fruit (Rubus idaeus L. cv. "Heritage") still on the plant. Drosophila suzukii puparia were recovered from fruit collected in an organic farm in Tafí del Valle, Tucumán, Argentina. One G. brasiliensis specimen was obtained from an isolated D. suzukii puparium. An additional 83 specimens, deposited in the entomological collection of the Museo de la Plata, Argentina, were also identified as G. brasiliensis. This parasitoid species is distributed in four biogeographical provinces of Argentina. The specimens of G. brasiliensis collected in Argentina are assumed to belong to a worldwide distributed and generalist lineage, parasitizing several Drosophila species. A taxonomic key of known Ganaspis species from Argentina is provided.


Resistance patterns, prevalence, and predictors of fluoroquinolones resistance in multidrug resistant tuberculosis patients.
Fluoroquinolones are the backbone of multidrug resistant tuberculosis treatment regimens. Despite the high burden of multidrug resistant tuberculosis in the country, little is known about drug resistance patterns, prevalence, and predictors of fluoroquinolones resistance among multidrug resistant tuberculosis patients from Pakistan. To evaluate drug resistance patterns, prevalence, and predictors of fluoroquinolones resistance in multidrug resistant tuberculosis patients. This was a cross-sectional study conducted at a programmatic management unit of drug resistant tuberculosis, Lady Reading Hospital Peshawar, Pakistan. Two hundred and forty-three newly diagnosed multidrug resistant tuberculosis patients consecutively enrolled for treatment at study site from January 1, 2012 to July 28, 2013 were included in the study. A standardized data collection form was used to collect patients' socio-demographic, microbiological, and clinical data. SPSS 16 was used for data analysis. High degree of drug resistance (median 5 drugs, range 2-8) was observed. High proportion of patients was resistant to all five first-line anti-tuberculosis drugs (62.6%), and more than half were resistant to second line drugs (55.1%). The majority of the patients were ofloxacin resistant (52.7%). Upon multivariate analysis previous tuberculosis treatment at private (OR=1.953, p=0.034) and public private mix (OR=2.824, p=0.046) sectors were predictors of ofloxacin resistance. The high degree of drug resistance observed, particularly to fluoroquinolones, is alarming. We recommend the adoption of more restrictive policies to control non-prescription sale of fluoroquinolones, its rational use by physicians, and training doctors in both private and public-private mix sectors to prevent further increase in fluoroquinolones resistant Mycobacterium tuberculosis strains.


Impact of uncertainty induced by fatality function on future tropical cyclone risk assessment.
Tropical cyclones (TCs) are among the deadliest extreme events occurring under a warming climate. Future TC risk assessment depend on TC projection from climate models and impact function relating TC to its possible consequence. Few studies have explored the uncertainty of impact function in future TC risk assessment compared to uncertainty in future TC characteristics. In this study, we investigate the uncertainty in TC fatality risk assessment induced by geographic and TC category-dependence of fatality function. We focus on all provinces in the mainland of China with historically recorded TC-induced fatalities and examine their TC fatality risks by assessing the difference in the annual average fatalities between current and future climate conditions. Synthetic TCs derived from four climate models and fatality functions parameterized from three grouped historical TC disaster datasets are used to observe the uncertainty induced by climate model and fatality function. Results show that the changes in the TC frequency, wind, TC-induced rainfall intensity, and exposure due to climate change in each province are dependent on the climate models. And the changes in the annual average fatality of each province are dependent on both the climate models and fatality functions. Climate models play a dominant role in determining the spatial pattern of future risk, while the fatality functions can alter the direction and magnitude of the risk change for certain provinces. Our results highlight the role of fatality function in detecting future TC risk under climate change, and inspire further TC impact studies that consider the heterogeneity of both climate conditions and geographical locations.


Towards an indigenous definition of health: an explorative study to understand the indigenous Ecuadorian people's health and illness concepts.
An intercultural society facilitates equitable and respectful interrelations. Knowing and understanding each other's sociocultural and linguitic contexts is a prerequisite for an intercultural society. This study explores the concepts of health and illness among healers of indigenous ethnicities in Southern Ecuador. A qualitative observational study with eleven focus groups was conducted in three locations in Southern Ecuador; a total of 110 participants the Shuar, Kichwa and Mestizo ethnic groups were included. A phenomenological and hermeneutic analysis was conducted. Fourteen main subtopics around of two predefined themes, i.e., "Health" and "Illness" were identified: 1) four bodies, 2) religiosity, 3) health as a good diet, 4) health as god's blessing or a gift, 5) health as balance/ harmony, 6) health as community and social welfare, 7) health as potentiality or a skill, 8) health as peacefulness, 9) heath as individual will, 10) illness as an imbalance, 11) illness as bad energy, 12) illness as a bad diet, 13) illness as suffering or worry, and 14) illness from God, Nature and People illness. By analysing all the topics' and subtopics' narratives, a health and illness definition was developed. The principal evidence for this new framework is the presence of interculturality as a horizontal axis in health. The indigenous perspective of health and illness focus on a balance between 4 bodies: the physical, spiritual, social and mental bodies. Additionally, "good health" is obtained through of the good diet and balanced/harmony. Indigenous healers in Southern Ecuador have views on health and illness that differ from the Western biomedical model of care. These different views must be recognized and valued in order to build an intercultural (health) system that empowers both ancestral and modern medical knowledge and healing.


Viral RNA in the influenza vaccine may have contributed to the development of ANCA-associated vasculitis in a patient following immunisation.
A number of large studies have demonstrated influenza vaccinations to be safe and effective. However, there have been some sporadic case reports, describing a temporal association of influenza vaccination with onset or relapse of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. The nature of this association, beyond time of occurrence, remains unknown. The presentation of a previously healthy patient who developed ANCA-associated vasculitis (AAV) shortly after influenza vaccination provided us with the rare opportunity to study the possible mechanisms behind this observation. We tested the ability of different types and batches of influenza vaccines to stimulate proteinase-3 ANCA (PR3-ANCA) production in vitro. We found that only some influenza vaccines stimulated PR3-ANCA production in this patient. We demonstrated that this unusual response was associated with those vaccines that contained viral ribonucleic acid (RNA), the natural ligand for Toll-like receptor-7. Exome sequencing of the patient's DNA did not show any mutation in any of the molecules associated with Toll-like receptor signalling. We propose that hyper-reaction to viral RNA in the influenza vaccine may have contributed to the development of AAV following influenza vaccination in this patient.


Phenotypic plasticity in Phlox : II. Plasticity of character correlations.
Three species of Phlox (Polemoniaceae) were grown in 6 greenhouse treatments. A variety of traits were recorded and the correlations among them were computed for each treatment. The phenotypic correlations between characters are significantly altered when plants are grown under different environmental conditions. These changes in correlation structure result from the differential phenotypic plasticity of traits. Partial correlations between flower production and other traits are also environment-dependent. Such changes can alter the intensity of, and possibly the response to, selection on traits correlated with fitness in natural plant populations.


Mental health in pregnant individuals during the COVID-19 pandemic based on a Swiss online survey.
The aim of our study was to evaluate the mental health of pregnant individuals during the early COVID-19 pandemic and the potential factors associated. A Swiss online survey was proposed to individuals who gave birth during the pandemic period from March 2020. The Edinburgh Postnatal Depression Scale (EPDS), Generalized Anxiety Disorder 7 questions (GAD-7), and Impact Event Scale-Revised (IES-R) were evaluated and used to defined mental health impairment as a composite outcome. From October, 2020 to February, 2021, 736 participants responded. The anxiety GAD-7 score was moderate in 9.6% and severe in 2.0%. The EPDS was moderate in 21.5% and severe in 32.9%. The IES-R was moderate in 10.3% and severe in 3.9%. Mental health impairment was reported in 37.0%. The association between the risk of mental health impairment and foreign nationality was significant (OR = 1.48; 95%CI [1.06-2.05]) as well as fetal and pregnancy worries because of coronavirus (OR = 1.46; 95% CI [1.08-1.98]) and 1.65; 95% CI [1.22-2.24]). Adjusted ORs were significant for foreign nationality (aOR = 1.51; 95%CI [1.07-2.13]) and pregnancy worries because of coronavirus (aOR = 1.62; 95%CI [1.10-2.40]). Pregnant people and especially foreign national have a high risk of mental health impairment during the pandemic.


Localization of neuropeptide Y-like immunoreactivity in the cat hypothalamus.
The distribution pattern of neuropeptide Y-like immunoreactivity (NPY-Li) in cat hypothalamus was studied using avidin-biotin modification of immunocytochemical method. This study showed cell bodies containing NPY-Li in the periventricular and the infundibular nuclei and also a moderate number of neurons with NPY-Li in the ventromedial nucleus, an observation not reported in earlier studies. Fibers with NPY-Li were noted throughout the hypothalamus, but most prominently within the periventricular regions. The location of NPY cells within the hypothalamus suggests the possibility of an interaction with dopaminergic and other proopiomelanocortinergic neurons.


Examining dog owners' beliefs regarding rabies vaccination during government-funded vaccine clinics in Grenada to improve vaccine coverage rates.
Vaccination of domestic pets is an important component of rabies control and prevention in countries where the disease is maintained in a wildlife reservoir. In Grenada, vaccine coverage rates were low, despite extensive public education and advertising of government-sponsored vaccine clinics where rabies vaccine is administered to animals at no cost to animal owners. Information was needed on reasons for decreased dog owner participation in government-funded rabies vaccination clinics. A total of 120 dog owners from 6 different parishes were asked to complete a questionnaire assessing their currently held beliefs about rabies vaccination and perception of the risk posed by rabies. Over 70% of respondents believed that problems in the organization and management of clinic sites could allow for fighting between dogs or disease spread among dogs, while 35% of owners did not believe that they had the ability or adequate help to bring their dogs to the clinic sites. Recommendations for improving vaccine coverage rates included: improved scheduling of clinic sites and dates; increased biosecurity at clinic locations; focused advertising on the availability of home visits, particularly for aggressive dogs or dogs with visible skin-related diseases such as mange; and the recruitment of community volunteers to assist with bringing dogs to the clinic sites.


Effect of IFN-alpha on CC1 4-induced fibrosis of the liver and immune status in mice of different age.
In young, adult, and old mice fibrosis was induced by administration of CC1(4) and treated with IFN-alpha; liver fibrosis was evaluated by morphometry of argyrophilic fibers, immune status by the splenocyte proliferative response. minimum immunosuppression and maximum antifibrotic effect were observed in young mice, while adult mice exhibited pronounced immunotoxicity and weak response to interferon therapy.


In vitro and ex vivo activity of new derivatives of acetohydroxyacid synthase inhibitors against Mycobacterium tuberculosis and non-tuberculous mycobacteria.
Sulfometuron methyl (SM) is an inhibitor of acetohydroxyacid synthase (AHAS), the first common enzyme in the branched-chain amino acid biosynthetic pathway, and shows activity against Mycobacterium tuberculosis both in vitro and in vivo. To develop AHAS inhibitor derivatives with more potent activity, 100 sulfonylurea analogues were screened for antimycobacterial activity against M. tuberculosis and non-tuberculous mycobacteria (NTM), and then evaluated for intracellular activity using mouse macrophages. Three new compounds with antimycobacterial activity comparable with that of SM were identified. These compounds exhibit significant activity against intracellular M. tuberculosis (including the drug-resistant M. tuberculosis strains), and NTM Mycobacterium abscessus and Mycobacterium kansasii, respectively.


[Investigation and confirmatory factor analysis of information collected with the four diagnostic methods in patients with bronchial asthma].
To investigate the information acquired through the four diagnostic methods of traditional Chinese medicine in patients with bronchial asthma, and to classify the syndrome types. Four hundred and thirty patients with bronchial asthma were randomly investigated. The information acquired through the four diagnostic methods was recorded and the database was established by Amos software, and then the data were analyzed by confirmatory factor analysis (CFA). After analyzing the data with 4 factors, 5 factors and 6 factors, we found that the results of CFA with 6 factors were in accordance with clinical practical experience. According to the results of CFA with 6 factors and with the standard regression coefficient 0.4 as primary and secondary critical points, the syndromes in patients with bronchial asthma can be classified into 5 types, which are syndromes of cold fluid retained in lung, phlegm-heat obstructing lung, wind-phlegm blocking lung, qi deficiency of lung and kidney and qi deficiency of spleen.


Enhancing Adolescent Risk Perception of Electronic Cigarette Use.
Adolescent electronic cigarette use has been steadily increasing since first being introduced commercially in 2007. The aim of this pilot study was to determine if adolescents who watched an educational video during a wellness visit would increase their perception of risk related to electronic cigarette use. Seventy-nine adolescents participated and were randomly assigned to the intervention (n = 40) or control (n = 39) group. Results included risk perception, perceived benefit, and provider discussion about electronic cigarettes. There was no statistical difference between intervention and control groups for electronic cigarette risk or perceived electronic cigarette benefit. Adolescents who watched the video intervention compared to those who did not watch a video intervention were significantly more likely to report having discussed electronic cigarettes with their provider (p < .001). Watching a video intervention on electronic cigarettes increased the likelihood of a reported discussion between provider/patient about electronic cigarettes but did not increase risk perception or decrease perceived benefit of electronic cigarettes. Utilizing video education is one tool that could potentially be used to augment provider education during wellness visits.


Pilot Testing of the MyCog Assessment: Rapid Detection of Cognitive Impairment in Everyday Clinical Settings.
Cognitive impairment (CI) and dementia can have profound social and emotional effects on older adults. Early detection of CI is imperative both to the identification of potentially treatable conditions and to provide services to minimize the effects of CI in cases of dementia. While primary care settings are ideal for identifying CI, it frequently goes undetected. We tailored a brief, iPad-based, cognitive assessment (MyCog) for primary care settings and piloted it in a sample of older adults. Eighty participants were recruited from an existing cohort study and completed a brief, in-person interview. CI was determined based on a diagnosis of dementia or CI in their medical record or based on a comprehensive cognitive battery performed within the past 18 months. MyCog had a sensitivity of 79% and specificity of 82%, offering a practical, scalable, primary care assessment for the routine case finding of cognitive impairment and dementia.


Endoscopic tympanoplasty type I using interlay technique.
Tympanoplasty using the interlay technique has rarely been reported in transcanal endoscopic ear surgery, unlike the underlay technique. This is because many surgeons find it challenging to detach the epithelial layer of the tympanic membrane using only one hand. However, the epithelial layer can be easily detached from the inferior part of the tympanic membrane. Another key point is to actively improve anteroinferior visibility even if the overhang is slight because most perforations and postoperative reperforations are found in the anteroinferior quadrant of the tympanic membrane. We report the application of the interlay technique in endoscopic tympanoplasty type I for tympanic perforations. We retrospectively reviewed the medical records of 51 patients who had undergone tympanoplasty using the interlay technique without ossiculoplasty between 2017 and 2020. We then compared the data with those of patients who underwent microscopic surgery (MS) using the underlay technique between 1998 and 2009 (n = 104). No other technique was used in each group during this period. Repair of tympanic membrane perforation and hearing outcomes were assessed for > 1 year postoperatively. The perforation sites were limited to the anterior, posterior, and anterior-posterior quadrants in 23, 1, and 27 ears, respectively. Perforations were closed in 50 of the 51 ears (98.0%), and the postoperative hearing was good (average air-bone [A-B] gap was 6.8 ± 5.8 dB). The surgical success rate for the repair of tympanic membrane perforation was not significantly different from the MS group (93.3%, P = 0.15). The average postoperative average A-B gap in the group that underwent the interlay technique was significantly different from that in the MS group (10.1 ± 6.6 dB, P < 0.01). The interlay technique should be considered as one of the treatment methods in endoscopic surgery for tympanic perforations. Further study of the postoperative outcomes of this procedure should be conducted to establish the optimal surgical procedure for tympanic perforations. This study was retrospectively approved by the Institutional Review Board of the Jikei University, Tokyo, Japan (approval number: 32-205 10286). Video abstract.


Characterization of the bioactive and mechanical behavior of dental ceramic/sol-gel derived bioactive glass mixtures.
Dental ceramics can be modified by bioactive glasses in order to develop apatite layer on their surface. One of the benefits of such modification is to prolong the lifetime of the fixed dental prosthesis by preventing the formation of secondary caries. Dental ceramic/sol-gel derived bioactive glass mixture is one of the options for this modification. In the current study, mixtures of dental ceramic/bioactive glass with different compositions were successfully produced. To evaluate their bioactive behavior, prepared samples were immersed in a simulated body fluid at various time intervals. The prepared and soaked specimens were characterized using Fourier transform infrared spectroscopy, X-ray diffractometry and scanning electron microscopy. Since bioactive glasses have deleterious effects on the mechanical properties of dental ceramics, 3-point bending tests were used to evaluate the flexural strength, flexural strain, tangent modulus of elasticity and Weibull modulus of the specimens in order to find the optimal relationship between mechanical and bioactive properties.


Cyclosporine-associated renal arteriopathy resulting in loss of allograft function.
Cyclosporine-associated arteriopathy was the cause of graft loss in 40 percent of all allografts that failed in a series of 200 consecutive cadaveric renal transplants. Arteriopathy was diagnosed by biopsy and renal uptake of indium 111m labeled platelets in the face of acute renal deterioration. A moderate thrombocytopenia and microangiopathic picture of hemolytic uremia was also present on peripheral blood smear. Immunofluorescence and histologic characteristics of the allograft biopsy specimens failed to show evidence for acute rejection: immunoglobulin M, immunoglobulin A, immunoglobulin G, C1q, C3, and C4 were not present, and there was no evidence of an interstitial or vascular mononuclear cellular infiltrate. Two clinical presentations have been described. In Group I (seven patients), anuria occurred rapidly within the first 2 weeks after transplantation. In Group II (nine patients) renal function gradually diminished 1 to 5 months after starting cyclosporine therapy. Fifteen of the 16 recipients had progressive and irreversible loss of renal function which was pathologically associated with fibrin deposition, intimal proliferation, and thrombotic occlusion of the cortical interlobular and arcuate arteries, with subsequent focal glomerular ischemia and cortical infarction. One recipient with rapid loss of renal function received an intraarterial allograft infusion of streptokinase and subsequent systemic heparinization, which resulted in return of normal allograft function. The syndrome of cyclosporine-associated arteriopathy has been linked to a lack of or reduced amounts of prostacyclin-stimulating factor or prostacyclin.


Structure-function and biological role of betacellulin.
Betacellulin (BTC) belongs to the epidermal growth factor (EGF) family of peptide ligands that are characterised by a six-cysteine consensus motif that forms three intra-molecular disulfide bonds crucial for binding the ErbB receptor family. BTC was initially described, purified and cloned from a mouse insulinoma cell line. BTC is proteolytically processed from a larger membrane-anchored precursor and is a potent mitogen for a wide variety of cell types. BTC binds and activates ErbB-1 and ErbB-4 homodimers and is further characterised by its unique ability to activate all possible heterodimeric ErbB receptors. BTC is widely expressed in most tissues and various body fluids, including milk. Expression is particularly high in the pancreas where it is thought to play a role in the differentiation of pancreatic beta cells. While much is known about the ErbB receptor binding characteristics of BTC and its effect on a variety of cultured cells under different conditions, the challenge that lies ahead is to determine the role of BTC in vivo. This review will focus on the structure of BTC and the various biological effects ascribed to this member of the EGF family.


Analysis of the carbohydrate-binding-module from Fragaria x ananassa α-L-arabinofuranosidase 1.
α-L-arabinofuranosidases (EC 220.127.116.11) are enzymes involved in the catabolism of several cell-wall polysaccharides such as pectins and hemicelluloses, catalyzing the hydrolysis of terminal non-reducing α-L-arabinofuranosil residues. Bioinformatic analysis of the aminoacidic sequences of Fragaria x ananassa α-L-arabinofuranosidases predict a putative carbohydrate-binding-module of the family CBM_4_9, associated to a wide range of carbohydrate affinities. In this study, we report the characterization of the binding affinity profile to different cell wall polysaccharides of the putative CBM of α-L-arabinofuranosidase 1 from Fragaria x ananassa (CBM-FaARA1). The sequence encoding for the putative CBM was cloned and expressed in Escherichia coli, and the resultant recombinant protein was purified from inclusion bodies by a Nickel affinity chromatography under denaturing conditions. The refolded recombinant protein was then subjected to binding assays and affinity gel electrophoresis, which indicated its ability to bind cellulose and also high affinity for homogalacturonans.


Combined excision, cryotherapy, and intraoperative mitomycin C (EXCRIM) for localized intraepithelial and squamous cell carcinoma of the conjunctiva.
To report the results of patients undergoing combined excision, cryotherapy, and intraoperative mitomycin-C (EXCRIM) for primary ocular surface squamous neoplasia (OSSN) METHODS: A retrospective review of a non-comparative interventional case series. Histopathologically confirmed primary localized (less than four clock hours) OSSN treated with EXCRIM using adjuvant 0.02 % mitomycin-C (MMC) were included in the study. The main outcome measures were recurrence and complications related to MMC. The study enrolled 28 eyes of 28 patients with OSSN with a median age of 64.5 (range 43 to 84) years. The mean tumor size was 6.9 × 4.35 mm. There was corneal involvement in 23 of 28 (82 %). Seven patients (21 %) had delayed epithelial healing. Two of eight patients (25 %) with squamous cell carcinoma (SCC) had positive lateral margins. There were no recurrences over a mean follow-up of 49 months (range 24 to 96). The excision of OSSN combined with cryotherapy and intraoperative MMC is effective with a low recurrence rate. Long-term follow-up yielded favorable results.


The basics of ring external fixator application and care.
The advantages of ring external fixation for correction of complex deformities of the foot and ankle include the ability to correct severe deformity, perform gradual correction, modify treatment during correction, and minimize neurovascular damage. External fixation can provide opportunities to operate on scarred and contracted tissues, preserve joints and joint function, maintain or gain foot length, and allow weight bearing during treatment.


Development and validation of a nomogram for postoperative sleep disturbance in adults: a prospective survey of 640 patients undergoing spinal surgery.
Postoperative sleep disturbance (PSD) is a prevalent clinical complication that may arise due to various factors. The purpose of this investigation is to identify the risk factors for PSD in spinal surgery and establish a risk prediction nomogram. The clinical records of individuals who underwent spinal surgery from January 2020 to January 2021 were gathered prospectively. The least absolute shrinkage and selection operator (LASSO) regression, along with multivariate logistic regression analysis, was employed to establish independent risk factors. A nomogram prediction model was devised based on these factors. The nomogram's effectiveness was evaluated and verified via the receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA). A total of 640 patients who underwent spinal surgery were analyzed in this investigation, among which 393 patients experienced PSD with an incidence rate of 61.4%. After conducting LASSO regression and logistic regression analyses using R software on the variables in training set, 8 independent risk factors associated to PSD were identified, including female, preoperative sleep disorder, high preoperative anxiety score, high intraoperative bleeding volume, high postoperative pain score, dissatisfaction with ward sleep environment, non-use of dexmedetomidine and non-use of erector spinae plane block (ESPB). The nomogram and online dynamic nomogram were constructed after incorporating these variables. In the training and validation sets, the area under the curve (AUC) in the receiver operating characteristic (ROC) curves were 0.806 (0.768-0.844) and 0.755 (0.667-0.844), respectively. The calibration plots indicated that the mean absolute error (MAE) values in both sets were respectively 1.2% and 1.7%. The decision curve analysis demonstrated the model had a substantial net benefit within the range of threshold probabilities between 20% and 90%. The nomogram model proposed in this study included eight frequently observed clinical factors and exhibited favorable accuracy and calibration. The study was retrospectively registered with the Chinese Clinical Trial Registry (ChiCTR2200061257, 18/06/2022).