Health literacy knowledge and experience survey: Cross-cultural adaptation and the psychometric properties of the Iranian nurse version.
Nurses' knowledge and Experience with Health Literacy can affect the treatment process, improving the quality of health care and effectively communicating with all clients. Evaluation of nurses' knowledge and experience requires a reliable instrument. This study aimed to translate cross-cultural adaptation and testing of Health Literacy Knowledge and Experience Survey (HL-KES). This cross-sectional methodological study was done during 2018-2019. The study was carried out in two stages: the first phase was designed to obtain a translation and cross-cultural equivalent of the (HL-KES), based on the World Health Organization (2018) and the Sousa and Rojjanasrirat (2011) Guidelines in six steps: preparation, forward translation, reconciliation, back translation, back translation review and pretesting and cognitive debriefing of the translated questionnaires. The second phase was conducted to evaluate the psychometric properties of the questionnaire. The content validity index and content validity ratio values of all items were >0.62 and 0.79, respectively. Based on the Kuder-Richardson formula, the reliability of the knowledge dimension was reported as 0.7. Furthermore, split-half coefficient for inter-rather reliability and test-retest were 0.76 and 0.96, respectively. The reliability of their experiences with the HL-KES was measured using Cronbach's alpha, in which it was 0.82. The Persian version of the instrument for assessing nurses' knowledge and experience with health literacy had good validity and reliability. It is recommended that it should be used in educational, clinical environments, and also in future research studies.


Macular thickness variation and interocular symmetry by gestational age in preterm school-age children.
To determine changes in macular thickness profile according to gestational age (GA) and to assess interocular symmetry in the macula of children born very preterm. In this cross-sectional study of preterm (n = 106) and term-born (n = 49) children 5-8 years of age at time of examination, optical coherence tomography was used to measure macula thickness as described in the ETDRS study. Statistical analyses included stratified and multivariable analyses. Foveal minimum thickness increased with decreasing GA (P for trend, <0.001; 254.7 ± 32.8 μm for children born at 24-25 weeks and 193.2 ± 32.8 μm in term-born children). Inner and outer area thickness differed for term and preterm children, but did not vary with the degree of prematurity (inner area, 267.0 ± 11.0 μm for 24-25 weeks' GA and 305.4 ± 11.8 μm for term children [P < 0.01]; outer ring, 305.5 ± 10.4 μm in extreme preterm and 271.0 ± 10.4 μm in term children [P < 0.01]). Interocular asymmetry in preterm children was not significant for most areas; the largest interocular difference was found in the central zone (16.3 ±16.6 μm). In our study cohort, children born very preterm examined at school age compared to term born children had greater central thickness with decreased foveal pit, decreased inner ring, and increased thickness of the outer ring. They did not show greater interocular asymmetry.


Histamine receptors and COVID-19.
Reports that the over-the-counter histamine H2 receptor antagonist famotidine could help treat the novel coronavirus disease (COVID-19) appeared from April 2020. We, therefore, examined reports on interactions between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and histamine receptor antagonists. A systematic literature search was performed by 19 September 2020, and updated on 28 October 2020, in PubMed, Scopus, Cochrane Library and Google Scholar using (COVID-19 OR coronavirus OR SARS-CoV-2) AND (histamine antagonist OR famotidine OR cimetidine). ClinicalTrials.gov was searched for COVID-19 and (famotidine or histamine). Famotidine may be a useful addition in COVID-19 treatment, but the results from prospective randomized trials are as yet awaited. Bioinformatics/drug repurposing studies indicated that, among several medicines, H1 and H2 receptor antagonists may interact with key viral enzymes. However, in vitro studies have to date failed to show a direct inhibition of famotidine on SARS-CoV-2 replication. Clinical research into the potential benefits of H2 receptor antagonists in managing COVID-19 inflammation began from a simple observation and now is being tested in multi-centre clinical trials. The positive effects of famotidine may be due to H2 receptor-mediated immunomodulatory actions on mast cell histamine-cytokine cross-talk, rather than a direct action on SARS-CoV-2.


The beneficial effect of total glucosides of paeony on psoriatic arthritis links to circulating Tregs and Th1 cell function.
Total glycosides of peony (TGP) is a natural immuno-modulatory drug extracted from traditional Chinese herb peony. It has been approved by State Food and Drug Administration for the treatment of rheumatoid arthritis. However, data of TGP effect on psoriatic arthritis (PsA) is still scarce. In this study, 19 patients with PsA received 12-week treatment of TGP, and clinical efficacy in joint manifestations was evaluated by DAS28 at weeks 0, 4, 8 and 12. Peripheral percentages of Tregs, Th1, Th2 and NK cells were analyzed, and serum Th1-type cytokines (IL-12, IFN-γ and TNF-α), Th2-type cytokines (IL-4, IL-5 and IL-10) as well as pro-inflammatory factors (IL-2, IL-6 and IL-8) were concomitantly examined. Six patients (32%) exhibited ≥25% decrease of DAS28 (responders). Interestingly, all responders displayed a continuous decrease in Treg and Th1 numbers during TGP treatment, concomitant with significant decreases in Th1-type cytokine levels. Serum IL-6 also showed a significant decline in responders. Non-responders lacked these sequential alterations. Thus, TGP merits further consideration as a promising therapeutic option for PsA. The result indicated that recovery of Tregs and Th1 may serve as prognostic markers to assess responsiveness to TGP treatment in PsA.


Triage of LSIL/ASC-US with p16/Ki-67 dual staining and human papillomavirus testing: a 2-year prospective study.
To investigate human papillomavirus (HPV) DNA testing and p16/Ki-67 staining for detecting cervical intraepithelial grade 2 or worse (CIN2+) and CIN3 in women referred to colposcopy with minor abnormal cervical cytology low-grade squamous intraepithelial lesions (LSIL) and atypical squamous cells of undermined significance (ASC-US). The clinical performance of both tests was evaluated as stand-alone tests and combined, for detection CIN2+ and CIN3 over 2 years. ThinPrep(®) liquid-based cytology (LBC) specimens were collected from 1349 women with repeat LSIL or ASC-US. HPV DNA was performed using Hybrid Capture. Where adequate material remained (n = 471), p16/Ki-67 overexpression was assessed. Clinical performance for detection of histologically diagnosed CIN2+ and CIN3 was calculated. Approximately 62.2% of the population were positive for HPV DNA, and 30.4% were positive for p16/Ki-67. p16/Ki-67 showed no significant difference in positivity between LSIL and ASC-US referrals (34.3% versus 28.6%; P = 0.189). Women under 30 years had a higher rate of p16/Ki-67 compared to those over 30 years (36.0% versus 26.6%; P = 0.029). Overall HPV DNA testing produced a high sensitivity for detection of CIN3 of 95.8% compared to 79.2% for p16/Ki-67. In contrast, p16/Ki-67 expression offered a higher specificity, 75.2% versus 40.4% for detection of CIN3. Combining p16/Ki-67 with HPV DNA improved the accuracy in distinguishing between CIN3 and <CIN3. The absolute risk of CIN3 increased from 15.6% in women who were HPV DNA positive to 27% in women positive for HPV DNA and p16/Ki-67. Those negative for HPV DNA and p16/Ki-67 had a low risk of 1.2% of CIN3. The addition of p16/Ki-67 to HPV DNA testing leads to a more accurate stratification of CIN in women presenting with minor cytological abnormalities.


Toxicity, of extracts of barley kernels inoculated withFusarium spp. toArtemia salina.
Toxicity toA. salina, of the Fusarium metabolites: deoxynivalenol (DON), its acetylated derivatives (3- and 15-AcDON), zearalenone (ZON), neosolaniol (NEO), nivalenol (NIV), T-2, HT-2 toxins, has been examined and compared with toxicity of extracts of barley kernels (8 cultivars and 4 lines) inoculated withFusarium culmorum, F. graminearum andF. sporotrichioides respectively. Estimated LC50 values were expressed as relative toxicity (RT) in mg DON/kg for samples inoculated withF. culmorum, F. graminearum or in mg T-2/kg forF. sporotrichioides inoculations.Toxicity of extracts of the same genotype/line kernels was compared among different pathogens used for inoculation and differences in Fusarium head blight susceptibility of different genotypes/lines inoculated with the sameFusarium strain were found. Significant correlation between toxicity of extracts (LC50, RT) and toxic metabolites concentration was found ([Formula: see text]; P = 0.01).Bioassays withA. Salina offer a fast, easy and inexpensive method to examine cereal genotypes susceptibility to Fusarium head blight and mycotoxins accumulation in kernels.


Basic aspects of absorption and fluorescence spectroscopy and resonance energy transfer methods.
Absorption and fluorescence spectroscopy are the heart of life science laboratory techniques. These two spectroscopic tools are sensitive, are easy to use, and can provide a wide range of information. The goal of this chapter is to familiarize the reader with some basic principles and applications of absorption and steady-state fluorescence spectroscopy. Selected applications are illustrated with examples.


Carbon isotope composition in relation to leaf gas exchange and environmental conditions in Hawaiian Metrosideros polymorpha populations.
Carbon isotope composition, photosynthetic gas exchange, and nitrogen content were measured in leaves of three varieties of Metrosideros polymorpha growing in sites presenting a variety of precipitation, temperature and edaphic regimes. The eight populations studied could be divided into two groups on the basis of their mean foliar δ13C values, one group consisting of three populations with mean δ13C values ca.-26‰ and another group with δ13C values ca.-28‰. Less negative δ13C values appeared to be associated with reduced physiological availability of soil moisture resulting from hypoxic conditions at a poorly drained high elevation bog site and from low precipitation at a welldrained, low elevation leeward site. Gas exchange measurements indicated that foliar δ13C and intrinsic wateruse efficiency were positively correlated. Maximum photosynthetic rates were nearly constant while maximum stomatal conductance varied substantially in individuals with foliar δ13C ranging from-29 to-24‰. In contrast with the patterns of δ13C observed, leaf nitrogen content appeared to be genetically determined and independent of site characteristics. Photosynthetic nitrogenuse efficiency was nearly constant over the range of δ13C observed, suggesting that a compromise between intrinsic water- and N-use efficiency did not occur. In one population variations in foliar δ13C and gas exchange with leaf cohort age, caused the ratio of intercellular to atmospheric partial pressure of CO2 predicted from gas exchange and that calculated from δ13C to be in close agreement only in the two youngest cohorts of fully expanded leaves. The results indicated that with suitable precautions concerning measurement protocol, foliar δ13C and gas exchange measurements were reliable indicators of potential resource use efficiency by M. polymorpha along environmental gradients.


Absorbed dose distribution of the auger emitters 67GA and 125I and the beta-emitters 67CU, 90Y, 131I, and 186RE as a function of tumor size, uptake, and intracellular distribution.
The influence of tumor volume, uptake of radioactive compounds in cells of tumors and normal tissues, and characteristics of the emitted ionizing particles on the efficacy of systemic radiation were studied. The influence of these variables was assessed using a point kernel approach combined with a distance histogram technique. Simulation calculations were performed to assess dose distributions for three tumor sizes (phi = 200 microns, 2 mm, or 2 cm) and six radionuclides: 67Ga, 125I, 67Cu, 90Y, 131I, and 186Re. The energy deposition patterns depended on the relation of the tumor size and range of the emitted particles. Selective uptake was especially important in cases where the range was short compared to the dimension of the tumor. To attain a high dose for treatment of micrometastases, the use of Auger and conversion electron emitters (67Ga and 125I) or beta-emitters with emission spectra including low energetic electrons (67Cu and 131I) was recommended. The results demonstrated the complementary nature of selectivity of energy deposition and crossfire. This implied that for tumor cells or areas with reduced uptake, crossfire from radioactivity in surrounding cells or areas with selective uptake would be provided by intermediate (conversion electrons) or long-range (beta-particles) emissions.


Iron content of Cambodian foods when prepared in cooking pots containing an iron ingot.
To investigate the effect of cooking with an iron ingot on the iron content of several water and Cambodian food preparations. Various food and water samples were prepared, in replicate, in glass and aluminium pots with and without an iron ingot. The samples were subjected to iron content analysis using standard ICP-OES procedures. Prepared with an ingot, the iron content was 76.3 μg iron/g higher in lemon water, 32.6 μg iron/g higher in pork soup and 3.3 μg iron/g higher in fish soup, than in the same foods prepared without an ingot. Acidity of the food samples was positively associated with iron leaching. Even when taking into account the low bioavailability of contaminant iron, approximately 75% of the daily iron requirement can be met by consuming 1L of lemon water prepared with an iron ingot. Its use may be a cheap and sustainable means of improving iron intake for those with iron-deficient diets.


Serum levels of soluble programmed cell death ligand 1 as a prognostic factor on the first-line treatment of metastatic or recurrent gastric cancer.
Immune checkpoint molecules are key targets for the treatment of various malignancies. Due to the heterogeneity of advanced gastric cancer (GC), the role of programmed cell death ligand 1 (PD-L1) expression as a tumor biomarker remains controversial. In this study, the prognostic value of soluble PD-L1 (sPD-L1) levels in serum samples was assessed in patients with metastatic GC. All patients received first-line treatment with fluoropyrimidine and platinum chemotherapy, and trastuzumab was added for HER2-positive patients. Serum levels of sPD-L1 were measured by enzyme-linked immunosorbent assay. Among 75 metastatic GC patients, the median serum sPD-L1 level was 0.704 ng/ml (range <0.156-3.214). Serum sPD-L1 was significantly higher in patients with a high versus a low white blood cell count at baseline. When the cutoff value was set as the median, multivariate analyses showed that high sPD-L1 levels were associated with worse overall survival compared with low sPD-L1 levels (HR 2.218, 95 % CI 1.139-4.320, P = 0.019). Regardless of HER2 status, overall survival tended to be shorter in patients with high sPD-L1 compared with low sPD-L1. There was no significant association between sPD-L1 level and progression-free survival on the first-line treatment of metastatic GC. High serum levels of sPD-L1 correlated with worse overall survival on the first-line chemotherapy in metastatic GC patients.


Protective effects of green tea on hepatotoxicity, oxidative DNA damage and cell proliferation in the rat liver induced by repeated oral administration of 2-nitropropane.
To evaluate the benefit of green tea in mitigating hazards caused by repeated exposure of 2-nitropropane (2NP), we examined the effects of the tea on toxic indices, oxidative DNA damage and cell proliferation in the liver of 2NP-treated rats. Male Fischer 344 rats were administered, by gastric intubation, a total of six doses of 60 mg/kg 2NP(L), or alternatively two doses of 90 mg/kg and then four doses of 120 mg/kg 2NP(H) during 2 weeks. Green tea infusion was given to the rats as drinking water 1 week before the 2NP treatments and throughout the experiment. Significant elevation of hepatotoxic indices was evident in the 2NP(H)-treated group, such as an increase of serum glutamic-oxaloacetic transaminase (GOT) activity and of hepatic lipid peroxidation, together with a decrease in hepatic glycogen and serum triglyceride, and degenerative changes in the hepatocytes. A dose-related increase was observed in oxidative DNA damage and cell proliferation in the liver. Green tea effectively inhibited all of above changes induced by 2NP treatment, suggesting that tea intake may be effective for preventing the hepatic injuries after chronic exposure to 2NP.


Localization in the CNA of adrenoceptors which facilitate a cardioinhibitory reflex.
In dogs (pentobarbitone, 25 mg/kg) the brain was removed rostrally to the pons, leaving the cerebellum intact (decerebrate animals). In other animals the cerebellum was additionally removed (bulbar animals). In all animals beta-adrenoceptors were blocked by toliprolol (5 mg/kg s.c.). Angiotensin (0.025-0.3mug/kg) was repeatedly injected i.v. and the resulting maximal reflex bradycardia was recorded. Intracisternal (i.ci.) injection of clonidine, 0.5 to 1 mug/kg, in decerebrate or i.v. injection of 10 or 30 mug/kg in bulbar animals significantly facilitated the reflex bradycardia. This effect was antagonised by a subsequent injection of piperoxan 50 mug/kg i.ci. in decerebrate or 1 mg/kg i.v. in bulbar animals. It is concluded that the facilitatory action of clonidine is mediated by alpha-adrenoceptors within the medulla oblongata.


Rhodium-catalyzed oxidative coupling through C-H activation and annulation directed by phosphonamide and phosphinamide groups.
Rhodium-catalyzed oxidative coupling reactions via C-H activation and annulation directed by phosphonamide and phosphinamide groups were developed under aerobic conditions, which produced benzazaphosphole 1-oxides and phosphaisoquinolin-1-oxides.


Patterns of distribution and accumulation of trace metals in Hysterothylacium sp. (Nematoda), Phyllodistomum sp. (Digenea) and in its fish host Hoplias malabaricus, from two neotropical rivers in southeastern Brazil.
Here we evaluated the potential for trace metal accumulation of two parasitic species, Hysterothylacium sp. (Nematoda) and Phyllodistomum sp. (Digenea), found parasitizing Hoplias malabaricus, a characiform fish also known as trahira, collected from two neotropical rivers, Jacaré-Pepira and Jacaré-Guaçú, in southeastern Brazil. Fish were collected between July 2017 and July 2019, totaling 90 fish specimens analyzed, 45 from each river. From fish, we take samples of three different tissues: muscle, intestine and liver. Along with the parasite samples taken from fish hosts, tissue samples were analyzed by an Inductively Coupled Plasma Mass Spectrometer (ICP-MS) for obtaining the trace metal (Al, Cr, Mn, Fe, Ni, Cu, As, Cd e Pb) concentrations. All elements were found in statistically higher concentrations in the parasites, both nematodes and digeneans, than in the host tissues, but in comparison, was observed that Hysterothylacium sp. had higher concentrations than those obtained in Phyllodistomum sp. We also found that uninfected fish had statistically higher concentrations of metals than infected ones. And in those who are infected, the size of the parasitic infrapopulations correlated negatively with the concentrations of trace metals obtained in the hosts tissues, that is, the concentrations in fish showed a tendency to decrease as the parasitic infrapopulations increased, or vice versa. In addition, our results show that the influence of the parasitic infrapopulations on metal concentrations in the fish host is not affected in cases of mono-infection or co-infection.


Evaluation of inguinal hernia repair using post-operative pain and quality of life metrics.
Elective inguinal hernia repair is a ubiquitous procedure that carries risks; chronic pain and impacts on quality of life (QoL) must be considered when advising patients around repair. The length of time from surgery date and impacts on quality of life are often limited to only a few years of follow-up and despite hernia repair being quite common, long-term outcomes are not often reported. A cohort of patients who had received Lichtenstein inguinal hernia repair over the previous 10 years were contacted and surveyed using the Brief Pain Inventory Short Form (BPI) to assess chronic pain and its effects on their QoL. Patient and operative factors were correlated with pain through linear regression and t-test analysis provided statistical significance for mean comparisons (P < 0.05). The rate of chronic pain was 17.2% with recurrence of 3.1% at an average post-operative interval of 5.84 years. Of the various metrics compared between groups, age was one of the only significant predictors of chronic pain with younger patients reporting higher pain. Further time from surgery also translated to significantly less pain with a difference of 1.3 years. BPI respondents identified pain that interfered to varying degrees in different aspects of life but had relatively low average magnitudes (range: 1.82/10-2.91/10). These long-term considerations of post-surgical impact should be considered alongside potential benefits when advising patients about surgery and may help moderate post-operative expectations to optimize the outcome of common inguinal hernia repairs.


A rosacea-like eruption induced by Tigason (Ro 10-9359) treatment.
A 67-year-old male patient, with a history of palmar psoriasis for 8 years, developed a rosacea-like eruption during Tigason (Ro-10-9359) treatment. Strict relationship between Tigason intake and skin symptoms was proved by double introduction of the drug and the patient's previous history. This retinoid side effect is very unusual and we are unable to give any explanation for it.


FTY720 induces ferroptosis and autophagy via PP2A/AMPK pathway in multiple myeloma cells.
Multiple myeloma (MM) is the second hematological plasma cell malignany and sensitive to fingolimod (FTY720), a novel immunosuppressant. Previous study shows FTY720-induced apoptosis and autophagy can cause cell death in MM cells, however, the high death rate cannot fully be explained. The study aims to investigate further mechanism of how FTY720 kills MM cells. Experiments are performed on 25 human primary cell samples and two MM cell lines by flow cytometry, fluorescence microscopy, and transmission electron microscopy. Expressions of relative factors are tested by qRT-PCR or western blot. Ferroptosis-specific inhibitors, deferoxamine mesylate (DFOM) and ferropstatin-1 (Fer-1), reverse FTY720-induced cell death in MM cells. Glutathione peroxidase 4 (GPX4) and soluble carrier family 7 member 11 (SLC7A11), key regulators of ferroptosis, are highly expressed in primary MM cells and can be decreased by FTY720 at the mRNA and protein level in MM cells. In addition, FTY720 induces other characteristic changes of ferroptosis. Furthermore, FTY720 can dephosphorylate AMP-activated protein kinase subunit ɑ (AMPKɑ) at the Thr172 site by activating protein phosphatase 2A (PP2A) and reduce the expression of phosphorylated eukaryotic elongation factor 2 (eEF2), finally cause MM cell death. Using LB-100, a PP2A inhibitor, AICAR, an agonist of AMPK, and bafilomycin A1 (Baf-A1), an autophagy inhibitor, we discover that FTY720 induces ferroptosis and autophagy through the PP2A/AMPK pathway, and ferroptosis and autophagy can reinforce each other. These results provide a new perspective on the treatment of MM.


Retinol-Binding Protein 4 Promotes Cardiac Injury After Myocardial Infarction Via Inducing Cardiomyocyte Pyroptosis Through an Interaction With NLRP3.
Background Acute myocardial infarction (AMI) is one of the leading causes of cardiovascular morbidity and mortality worldwide. Pyroptosis is a form of inflammatory cell death that plays a major role in the development and progression of cardiac injury in AMI. However, the underlying mechanisms for the activation of pyroptosis during AMI are not fully elucidated. Methods and Results Here we show that RBP4 (retinol-binding protein 4), a previous identified proinflammatory adipokine, was increased both in the myocardium of left anterior descending artery ligation-induced AMI mouse model and in ischemia-hypoxia‒induced cardiomyocyte injury model. The upregulated RBP4 may contribute to the activation of cardiomyocyte pyroptosis in AMI because overexpression of RBP4 activated NLRP3 (nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3) inflammasome, promoted the precursor cleavage of Caspase-1, and subsequently induced GSDMD (gasdermin-D)-dependent pyroptosis. In contrast, knockdown of RBP4 alleviated ischemia-hypoxia‒induced activation of NLRP3 inflammasome signaling and pyroptosis in cardiomyocytes. Mechanistically, coimmunoprecipitation assay showed that RBP4 interacted directly with NLRP3 in cardiomyocyte, while genetic knockdown or pharmacological inhibition of NLRP3 attenuated RBP4-induced pyroptosis in cardiomyocytes. Finally, knockdown of RBP4 in heart decreased infarct size and protected against AMI-induced pyroptosis and cardiac dysfunction in mice. Conclusions Taken together, these findings reveal RBP4 as a novel modulator promoting cardiomyocyte pyroptosis via interaction with NLRP3 in AMI. Therefore, targeting cardiac RBP4 might represent a viable strategy for the prevention of cardiac injury in patients with AMI.


Performance and process in collective and individual memory: the role of social decision schemes and memory bias in collective memory.
To assess performance and processes in collective and individual memory, participants watched two job candidates on video. Beforehand, half the participants were told they would be tested on their memory of the interviews, and the other half were asked to make a decision to hire one of the candidates. Afterwards, participants completed a recognition memory task in either a group or individual condition. Groups had better recognition memory than individuals. Individuals made more false positives than false negatives and groups exaggerated this. Post-hoc analysis found that groups only exaggerated the tendency towards false positives on items that reflected negatively on the job candidate. There was no significant difference between instruction conditions. When reaching consensus on the recognition task, groups tended to choose the correct answer if at least two members had the correct answer. This method of consensus is discussed as a factor in groups' superior memory performance.


E-cadherin transcriptional downregulation by promoter methylation but not mutation is related to epithelial-to-mesenchymal transition in breast cancer cell lines.
Using genome-wide expression profiling of a panel of 27 human mammary cell lines with different mechanisms of E-cadherin inactivation, we evaluated the relationship between E-cadherin status and gene expression levels. Expression profiles of cell lines with E-cadherin (CDH1) promoter methylation were significantly different from those with CDH1 expression or, surprisingly, those with CDH1 truncating mutations. Furthermore, we found no significant differentially expressed genes between cell lines with wild-type and mutated CDH1. The expression profile complied with the fibroblastic morphology of the cell lines with promoter methylation, suggestive of epithelial-mesenchymal transition (EMT). All other lines, also the cases with CDH1 mutations, had epithelial features. Three non-tumorigenic mammary cell lines derived from normal breast epithelium also showed CDH1 promoter methylation, a fibroblastic phenotype and expression profile. We suggest that CDH1 promoter methylation, but not mutational inactivation, is part of an entire programme, resulting in EMT and increased invasiveness in breast cancer. The molecular events that are part of this programme can be inferred from the differentially expressed genes and include genes from the TGFbeta pathway, transcription factors involved in CDH1 regulation (i.e. ZFHX1B, SNAI2, but not SNAI1, TWIST), annexins, AP1/2 transcription factors and members of the actin and intermediate filament cytoskeleton organisation.


Benign schwannoma of the pterygopalatine fossa with intracranial extension: a case report.
The authors present a rare case of benign schwannoma arising in the pterygopalatine fossa. The patient, an 18-year-old female, initially noticed blurring of her left eye but later, sudden loss of her left vision occurred. Radiological and computed tomographic studies outlined a mass occupying the left pterygopalatine fossa, which extended into the middle cranial fossa, the maxillary, ethmoid and sphenoid sinuses and the orbit. The histology of a transantral biopsy was reported as a benign schwannoma. The tumor was successfully removed by a transmaxillary approach. The eye symptoms disappeared four weeks following surgery. The nerve of origin of the tumor was not identified. The authors posturate that erosion of the skull base with mild to moderate extension into the middle cranial fossa, does not appear to be a contraindication for excising a schwannoma by the transmaxillary approach in this area.


Epithelial cell adhesion molecule-positive circulating tumor cells as predictive biomarker in patients with prostate cancer.
To assess the use of circulating tumor cells (CTCs) as a longitudinal endpoint factor for clinical monitoring of patients with prostate cancer and to evaluate the association among the baseline CTC number, various clinical characteristics, and survival. The CTCs were enumerated using the CellSearch Food and Drug Administration-cleared CTC kit in 202 patients with prostate cancer. Variables, including metastatic site, prostate-specific antigen level, Gleason score, testosterone level, and use of androgen treatment, were tested for association with the CTC number. The probability of patient survival over time was estimated using the Kaplan-Meier method. The baseline CTC numbers were strongly associated with survival (P <.0001), with overall survival significantly poorer in patients with ≥5 CTCs. Significantly greater CTC numbers were observed in patients with bone metastasis (mean 41.12 CTCs) than in those with lymph node metastasis (mean 2.53 CTC, P = .026). Analysis of the association between the CTC count and prostate-specific antigen level revealed a weak positive correlation (correlation coefficient r = 0.2695, P = .0007). The CTC number also correlated with the Gleason score (P = .0138) and lower testosterone level (P <.0001). Patients without androgen depletion had significantly lower CTC numbers (mean 2.70) than those with androgen depletion (mean 26.39, P <.0001). The baseline CTC counts were predictive of patient survival and correlated significantly with the clinical characteristics of patients with prostate cancer. Our study results have confirmed previous findings that support the use of CTC enumeration as a prognostic biomarker for patients with prostate cancer.


Effects of mitogenic agents upon glucocorticoid action in human tonsillar T-lymphocytes.
The treatment of human tonsillar T-lymphocytes with 4-phorbol 12-myristate 13-acetate (PMA), resulted in about two fold increase in glucocorticoid receptor (GR) number, without any significant change in the receptor affinity. This increase disappeared in the presence of cycloheximide. Alone, PMA and calcium ionophore A23187 did not affect, but together stimulated, like phytohaemagglutinin (PHA), leucine and, in particular, thymidine incorporation. PMA enhanced slightly the stimulatory effect of PHA. Alone, these agents failed to alter the suppressive effect of dexamethasone on thymidine and leucine incorporation; however, PMA-A23187 and PMA-PHA combinations appeared to antagonize the suppression by dexamethasone.


Simultaneous determination of nimesulide and its four possible metabolites in human plasma by LC-MS/MS and its application in a study of pharmacokinetics.
In this study, it was the first time that we simultaneously quantified nimesulide and its possible metabolites M1, M2, M3 and M4 by employing liquid chromatography-tandem mass spectrometry (LC-MS/MS). Nimesulide-d5 was used as internal standard (IS) for validation. Analytes and IS were recovered from human plasma by protein precipitation with acetonitrile. Prepared plasma samples were analyzed under the same LC-MS/MS conditions, and chromatographic separation was realized by using an Ultimate C18 column, with run time being 5min for each sample. Our results showed that various analytes within their concentration ranges could be quantified accurately by using the method. Mean intra- and inter-day accuracies ranged from -4.8% to 4.8% (RE), and intra- and inter-assay precision ≤6.2% (RSD). The following parameters were validated: specificity, recovery, matrix effects, dilution integrity, carry-over, sample stability under a variety of storage and handling conditions (room temperature, freezer, freeze-thaw and post-preparative) and stock solution stability. Pharmacokinetics of nimesulide and its metabolites were calculated based on the analysis of samples collected from twelve Chinese healthy volunteers after single oral dose of 100mg nimesulide tablets. By applying the pharmacokinetic determination into human samples, we preliminarily detected a new metabolite of nimesulide (M4*), and the concentration of M4* was relatively higher in plasma. Furthermore, we predicted part of conceivable metabolism pathway in plasma of after oral administration of 100mg nimesulide tablets. This research provided an experimental basis for further studies on metabolic activation and biotransformation of nimesulide, and for more comprehensive conjecture of its metabolic pathways.


Function of saposin C in the reconstitution of glucosylceramidase by phosphatidylserine liposomes.
The function of saposin C (Sap C), a glucosylceramidase activator protein, in the enzyme stimulation by phosphatidylserine (PS) liposomes has been investigated. Using gel filtration experiments evidence was obtained for Sap C binding to PS large unilamellar vesicles (LUV) but not to glucosylceramidase. PS LUV, which by themselves are unable to tightly bind and stimulate the enzyme, acquire the capacity to also bind the enzyme after interaction with Sap C, making it express its full activity. Our results indicate that the primary step in the Sap C mode of action resides in its association with PS membranes; in turn, this association promotes the interaction between the membranes and glucosylceramidase.


Beyond thrice-weekly hemodialysis.
The frequency, length, and dose of hemodialysis (HD) have empirically evolved during the past four decades. The relationships among these variables and their influence on clinical outcomes are complex. Despite the lack of controlled studies and the selection bias inherent to cohorts studied with enhanced or intensified HD prescriptions, this review explores the impact of frequency, length, and dose of HD on clinical outcomes. The experiences with frequent HD make a formidable case for frequent therapies. The data show that quotidian regimens are associated with the best biochemical profiles, volume and hypertension control, and nutritional status, but do not provide the evidence for superior survival when compared to long nocturnal thrice-weekly or every-other-day conventional HD. The correlation between frequency and clinical outcomes seems evident, but not likely to be linear. Perhaps the greatest benefits are achieved from the simple avoidance of 48 hr without dialysis. Considering the additional cost and patient involvement with daily dialysis compared to every-other-day dialysis, it is logical to include the latter in future controlled studies on the benefits of frequent HD.


Urinary albumin excretion after donor nephrectomy.
Surgical ablation of renal tissue in animals leads to compensatory hyperfiltration, hypertension, and focal glomerular sclerosis in remnant nephrons, in association with albuminuria; the detection of slightly elevated urinary albumin (microalbuminuria) has been shown to predict later, more severe renal disease in diabetics. To determine whether unilateral nephrectomy in humans initiates a similar pathogenetic sequence, we measured urinary albumin excretion (UalbV), total protein excretion (UprotV), creatinine clearance (Ccreat) and blood pressure in 22 transplant donors before and at intervals up to 3 years after donor nephrectomy. Urinary albumin was determined using a sensitive enzyme immunoassay (ELISA). Mean Ccreat fell on average to 68% of prenephrectomy values at all times after nephrectomy, indicating a rise of 33% in average single nephron filtration rate. Mean absolute and fractional albumin excretion rates and UprotV values were transiently elevated one week postnephrectomy, but returned thereafter to values not significantly different from prenephrectomy values. Blood pressure rose slightly, but significantly, with time after nephrectomy. Average increases of 10 mm and 5 mm in systolic and diastolic pressures, respectively, were noted by 2 years after surgery. In this study, there was no evidence of glomerular injury from hyperfiltration in the 3 years following donor nephrectomy.


CSF levels of cyclic nucleotides in primary intracranial neoplasms: a preliminary report.
Recent evidence indicates that cyclic nucleotides are of importance for general and neurosurgical oncology, especially with respect to the contact-inhibition mechanisms and tumour cell growth. This preliminary report deals with the CSF levels of c-AMP and c-GMP in primary neoplasms in children and to problems related to the blood-brain barrier. Some cases of medulloblastoma were studied as well as a few cases of brain stem glioma and cystic astrocytoma. The importance of some rather unusual findings seems undebatable, i.e., the marked increase in c-GMP values usually observed in medulloblastoma and the decrease of c-AMP, that is fairly common in all malignant neoplasms. The main changes in the c-AMP/c-GMP ratio are also discussed.


Memory loss after electroconvulsive treatment--may the sudden alleviation of depression-inducing memories explain patient despair?
Electroconvulsive treatment (ECT) has developed over 70 years to a modern, effective way of lifting depressive moods. Memory loss after electroconvulsive treatment is the only remaining relevant criticism of the treatment modality when considering the overall rate of remission from this treatment compared to all other treatment modalities. A depressive state impedes memory. After treatment memory improves on several qualities of cognition. However, comparing a person's memory ability from the months before depression started to the level after a course of ECT is never done, of obvious reasons. There are great clinical difficulties explaining who would develop memory problems, regardless of stimulation techniques, age or sex of the patient. The memory loss seen in some patients undergoing electroconvulsive treatment (ECT) is not explained by the treatment alone. After ECT unpleasant memories are disclosed rapidly and the patient may unconsciously try to defend herself by extending memory repression to other areas of memory. This may be unrelated to treatment modality, number of sessions or severity of depression. Psychological factors may partly explain why some patients unfold memory problems when the depression is rapidly lifted, rather than the treatment modality itself.


Comparative effect of certain organophosphorus compounds and other chemicals on whole blood, plasma and tissue cholinesterase activity in goats.
Cholinesterase (ChE) activity was measured in whole blood, plasma and certain tissues of goats experimentally poisoned with certain organophosphates, organochlorines, heavy metals and anthelmintic drugs. The enzyme activity was only inhibited by the organophosphorus compounds and not by any of the other substances used. The greatest inhibition occurred in the brain, although the blood ChE activity was concurrently inhibited in a similar degree.


Lipolytic action of glucagon-like peptides in isolated rat adipocytes.
The lipolytic effect of GLP-1(1-36)-amide, GLP-1(7-36) amide and GLP-2 [proglucagon(126-159)] has been studied in isolated rat adipocytes. Glycerol release and cyclic AMP content were measured after incubation of adipocytes with GLPs and results have been compared with those obtained in the presence of glucagon. GLP-1(7-36)-amide and GLP-1(1-36)-amide at 10(-8), 10(-7) and 10(-6) M concentrations activated glycerol release, the truncated peptide having a more potent effect. On the other hand, GLP-2 had no effect on glycerol release. Also, it has been found that 10(-6) M GLP-1(7-36)-amide increases cyclic AMP content in adipocytes and does not compete with glucagon binding. These results demonstrate that GLP-1(7-36)-amide has a lipolytic effect on isolated rat adipocytes through different receptors than glucagon.


Evaluation of head motility and posture in cats with horizontal torticollis.
Unilateral electrolytic lesions and injections of 6-hydroxydopamine (6-OHDA) and 5,7-dihydroxytryptamine (5,7-DHT) were made in structures and pathways linked to the striatopallidal system of cats. The effects of such lesions on horizontal head symmetry and head motility were measured in restrained cats by electrogoniometry. Analysis of electrogoniometric recordings provided (i) an index of head symmetry, (ii) net time-course patterns of head turning in degrees per minute, and (iii) time-course patterns of head motility, measured in number of head movements per minute. All lesions except the electrolytic lesion of the superior colliculus induced an enduring horizontal head asymmetry. Electrolytic, 5,7-DHT, and 6-OHDA lesions made in the medial forebrain bundle induced a nearly total head asymmetry (95 to 98%). Cats in which an electrolytic lesion was made in the substantia nigra reticulata (SNR) also displayed an important head asymmetry (80%). For all lesions except the SNR lesions the direction of the induced head asymmetry was ipsilateral. In 6-OHDA-lesion cats a marked and consistent decrease head motility was also observed. The combined evaluation of head posture and head movements indicated that according to the lesion, head symmetry and head motility are disturbed in different manners. The results further emphasized the complementary contribution of the caudate and SNR in regulation of head symmetry and indicated the advantages of the electrogoniometric method for selectively measuring head posture and movements.


Blood Transfusion: Cost, Quality, and Other Considerations for the Surgical Management of the Critically Ill.
This article explores the average overall costs of blood transfusion for critically ill surgical patients and in particular explores the evidence supporting reduction of transfusion as part of guideline-based care in cardiothoracic surgical patients. Average cost data compiled from various sources are presented and quality and outcome considerations in blood transfusion in the critically ill are reviewed. Multiple strategies that have a high level of evidence to support their use in this population are noted.


[Peripheral arterial pseudo-aneurysm in Behçet's disease: Report of two cases].
Behçet's disease is a systemic vasculitis of unknown etiopathogenesis. Arterial events such as pseudo-aneurysms are rare and may be the mode of occurrence of the disease. These pseudo-aneurysms tend, regardless of size, to progress rapidly to life-threatening rupture. We report two cases of arterial pseudo-aneurysms that ruptured. Treatment consisted of surgical repair in one case and arterial ligation in the other; the postoperative course was uneventful in both cases.


Successful treatment with infliximab for Behçet disease during pregnancy.
To report a case of successful treatment with infliximab for Behçet disease (BD) during pregnancy. A case report. A 30-year-old woman was diagnosed with BD at 12 weeks of pregnancy. Additional symptoms occurred, and infliximab at a dose of 5 mg/kg body weight was initiated at 18 weeks and repeated. All symptoms improved, and a 3950-g infant was delivered uneventfully without any abnormality at 39 weeks. A few weeks after delivery, uveitis and systemic symptoms relapsed. Infliximab was reinitiated and all symptoms were resolved. Infliximab may be safe and effective for BD during pregnancy.


Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor.
More and more targeted agents become available for B cell malignancies with increasing precision and potency. The first-in-class Bruton's tyrosine kinase (BTK) inhibitor, ibrutinib, has been in clinical use for the treatment of chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's macroglobulinemia. More selective BTK inhibitors (ACP-196, ONO/GS-4059, BGB-3111, CC-292) are being explored. Acalabrutinib (ACP-196) is a novel irreversible second-generation BTK inhibitor that was shown to be more potent and selective than ibrutinib. This review summarized the preclinical research and clinical data of acalabrutinib.


Therapeutic potential of the sphingosine kinase 1 inhibitor, PF-543.
PF-543 is a sphingosine kinase 1(SPHK1)inhibitor developed by Pfizer and is currently considered the most potent selective SPHK1 inhibitor. SPHK1 catalyses the production of sphingosine 1-phosphate (S1P) from sphingosine. It is the rate-limiting enzyme of S1P production, and there is substantial evidence to support a very important role for sphingosine kinase in health and disease. This review is the first to summarize the role and mechanisms of PF-543 as an SPHK1 inhibitor in anticancer, antifibrotic, and anti-inflammatory processes, providing new therapeutic leads and ideas for future research and clinical trials.


A roadmap to defining the clinical reportable ranges of chemistry analytes: Increasing automation efficiency and decreasing manual dilutions.
Proper utilization of resources is an important operational objective for clinical laboratories. To reduce unnecessary manual interventions on automated instruments, we conducted a workflow analysis that optimized dilution parameters and reporting of abnormally high chemistry results for the Beckman AU series of chemistry analyzers while maintaining clinically acceptable reportable ranges. Workflow analysis for the Beckman AU680/5812 and DxC800 chemistry analyzers was performed using historical data. Clinical reportable ranges for 53 chemistry analytes were evaluated. Optimized dilution parameters and upper limit of reportable ranges for the AU680/5812 instruments were derived and validated to meet these reportable ranges. The number of specimens that required manual dilutions before and after optimization was determined for both the AU680/5812 and DxC800, with the DxC800 serving as the reference instrument. Retrospective data analysis revealed that 7700 specimens required manual dilutions on the DxC over a 2-y period. Using our optimized AU-specific dilution and reporting parameters, the data-driven simulation analysis showed a 61% reduction in manual dilutions. For the specimens that required manual dilutions on the AU680/5812, we developed standardized dilution procedures to further streamline workflow. We provide a data-driven, practical outline for clinical laboratories to efficiently optimize their use of automated chemistry analyzers. The outcomes can be used to assist laboratories wishing to improve their existing procedures or to facilitate transitioning into a new line of instrumentation, regardless of the instrument model or manufacturer.


Turpentine-induced decrease of alpha 1-foetoprotein in the serum of the developing rat: a novel parameter of the inflammatory response.
The acute phase of an inflammation induced in young rats, at various ages between 1 and 21 days after birth, by a single subcutaneous turpentine injection, is accompanied by a 35%-45% decrease of the alpha 1-foetoprotein serum concentrations. This fall is demonstrated with equilibrium dialysis binding methods, evidencing the loss of about 1/3 of the high affinity estrogen binding sites characteristic for the rat foetoprotein, as well as by specific immunoassay of the foetoprotein concentrations. This negative response is coincidental with classical inflammatory changes of the plasma proteins, similar to those defined in adults: in particular we evidence 5 to 10 fold rises of haptoglobin, as early as the first post-natal day. We discuss the implications of these findings for ontogenic and mechanistic aspects of the inflammatory response.


Ganglion cysts of the shoulder: technique of arthroscopic decompression and fixation of associated type II superior labral anterior to posterior lesions.
Ganglion cysts of the shoulder and concomitant suprascapular nerve compression should be considered in the differential diagnosis of shoulder pain. They are associated commonly with labral tears, most commonly SLAP lesions. MRI has become commonplace in evaluating shoulder pain and has led to the increased awareness of shoulder cysts. MRI accurately demonstrates the size and location of ganglions, which is critical when planning surgical intervention. It also has shown the frequent association of intra-articular pathology with these cysts. Despite that MRI can detect atrophy, the diagnosis of suprascapular nerve compression can be confirmed only by EMG/NCS, because the presence of a cyst does not necessarily mean the nerve is compressed. Likewise, a positive EMG does not confirm that the compression is caused by a ganglion cyst. EMG/NCVs are necessary for confirming the diagnosis and evaluating nerve and muscle function. A trial of nonoperative management is warranted; however, this is associated with a high failure rate. Aspiration techniques are successful for decompression of the cysts and initial pain relief; however, the intra-articular pathology is not addressed and there is a higher rate of recurrence. Open resection of the ganglion cyst is successful; however, the intra-articular labral tears are not addressed, which can lead to recurrence and the morbidity of the cyst excision is not warranted. Shoulder arthroscopy has led to the identification of associated intra-articular pathology such as SLAP lesions. These were not appreciated previously with open surgery and therefore were not addressed. Arthroscopic techniques have evolved to allow decompression of the ganglion cysts and repair of the labral lesions. This should decrease the possibility of recurrence of the cyst by eliminating the cyst and the pathologic lesion that created it. Arthroscopic excision also avoids much of the morbidity of the open approach and allows intra-articular pathology to be addressed concomitantly. This point has been emphasized by other investigators also. Furthermore, because of the limited surgical dissection, rehabilitation is able to begin earlier, with less patient discomfort and more prompt return to normal activities.


Cerebellar molecular layer interneurons are dispensable for cued and contextual fear conditioning.
Purkinje cells are the only output cell of the cerebellar cortex. Their spatiotemporal activity is controlled by molecular layer interneurons (MLIs) through GABAA receptor-mediated inhibition. Recently, it has been reported that the cerebellar cortex is required for consolidation of conditioned fear responses during fear memory formation. Although the relevance of MLIs during fear memory formation is currently not known, it has been shown that synapses made between MLIs and Purkinje cells exhibit long term plasticity following fear conditioning. The present study examined the role of cerebellar MLIs in the formation of fear memory using a genetically-altered mouse line (PC-∆γ2) in which GABAA receptor-mediated signaling at MLI to Purkinje cell synapses was functionally removed. We found that neither acquisition nor recall of fear memories to tone and context were altered after removal of MLI-mediated inhibition.


Deep Learning in Therapeutic Antibody Development.
Deep learning applied to antibody development is in its adolescence. Low data volumes and biological platform differences make it challenging to develop supervised models that can predict antibody behavior in actual commercial development steps. But successes in modeling general protein behaviors and early antibody models give indications of what is possible for antibodies in general, particularly since antibodies share a common fold. Meanwhile, new methods of data collection and the development of unsupervised and self-supervised deep learning methods like generative models and masked language models give the promise of rich and deep data sets and deep learning architectures for better supervised model development. Together, these move the industry toward improved developability , lower costs, and broader access of biotherapeutics .


Early diagnosis of pancreatic infection by computed tomography-guided aspiration.
We performed 92 computed tomography-guided percutaneous needle aspirations of pancreatic inflammatory masses in 60 patients suspected of harboring pancreatic infection. Thirty-six patients (60%) were found by Gram stain and culture to have a total of 41 separate episodes of pancreatic infection. Among 42 aspirates judged to be infected by computed tomography-guided aspiration, all but one were confirmed by surgery or indwelling catheter drainage. Among 50 aspirates judged to be sterile, no subsequent evidence of infection was found. All patients tolerated the procedure well and no complications were noted. As a result of this technique, we observed that pancreatic infection occurs earlier than has been previously appreciated (within 14 days of the onset of pancreatitis in 20 of the 36 patients) and that infection may recur during prolonged bouts of pancreatitis. We conclude that guided aspiration is a safe, accurate method for identifying infection of the pancreas at an early stage.


Isometric force development in human horizontal eye muscles and pulleys during saccadic eye movements.
The connective tissue elements forming the check ligaments and portals of the human eye muscles have recently been ascribed with a pulley function. Active positioning of the pulleys over orbital layer contraction during eye movements has been suggested. Other studies have instead demonstrated fibrous tissue connections between all parts of the muscle and the pulleys. We aimed to compare the isometric force developed at the muscle tendon and at the pulleys of the horizontal eye muscles, and to investigate which eye muscle structures might exert force on the pulleys. Isometric force development was recorded from the lateral and medial rectus muscles in six patients operated for strabismus under topical anaesthesia. Two strain gauge probes were used, each attached with 5-0 silk sutures either to the muscle tendon or to the pulley. The eye muscles were activated by horizontal saccadic eye movements in steps from 30 degrees in the off-direction to 30 degrees in the on-direction of the muscles. The forces developed at the tendon and pulley were almost identical with respect to amplitude and other parameters. No differences were found in forces developed at the pulleys of the medial and lateral rectus muscles. The results support the presence of fibrous tissue connections between all eye muscle fibres and pulley structures, rather than orbital fibre control of the pulley.


The origin of the C-genome and cytoplasm of Avena polyploids.
The contribution of C-genome diploid species to the evolution of polyploid oats was studied using C-genome ITS-specific primers. SCAR analysis among Avena accessions confirmed the presence of C-genome ITS1-5.8S-ITS2 sequences in the genome of AACC and AACCDD polyploids. In situ hybridization and screening of more than a thousand rRNA clones in Avena polyploid species containing the C-genome revealed substantial C-genome rRNA sequence elimination. C-genome clones sequenced and Maximum Likelihood Parsimony analysis revealed close proximity to Avena ventricosa ITS1-5.8S-ITS2 sequences, providing strong evidence of the latter's active role in the evolution of tetraploid and hexaploid oats. In addition, cloning and sequencing of the chloroplastic trnL intron among the most representative Avena species verified the maternal origin of A-genome for the AACC interspecific hybrid formation, which was the genetic bridge for the establishment of cultivated hexaploid oats.


Somatic symptom disorder in primary care: A collaborative approach.
The guidance presented here will help you to counsel patients and work with other caregivers in a biopsychosocial approach.


Improvement of the lipid profile with exercise in obese children: a systematic review.
The objective of this systematic review was to assess the effectiveness of different physical exercise interventions on the lipid profile (high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG)) of obese children. A computerized search was made of seven databases using keywords. Effect sizes (ES) and 95% confidence intervals were calculated, and the heterogeneity (I(2)) of the studies was estimated using Cochran's Q-statistic applied to the effect size means. The studies were grouped according to the intervention program-aerobic alone or combined (aerobic fitness, strength, and flexibility). Seven studies were selected for review as satisfying the inclusion criteria. Six were randomized controlled trials (n=318) and one was a controlled clinical trial (groups not randomly assigned) (n=38). The main cumulative evidence indicates that the programs based on aerobic exercise alone have a moderate (ES=-0.49; I²=87) and a large effect (ES=-0.55; I²=77) on LDL-C and TG concentrations, respectively; and the programs based on combined exercise have a moderate effect (ES=0.50; I²=0) on HDL-C concentration. The programs based on aerobic exercise (60 min, 3 times/week, ≤75% maximum heart rate) improve the LDL-C and TG concentrations. Moreover, the programs based on combined exercise (≥60 min, >75% maximum heart rate) also improve the HDL-C concentration.


Three-Dimensional Confocal Analysis of Chromosome Positioning Coupled with Immunofluorescence in Mouse Sperm Nuclei.
Male infertility is associated with several causes affecting the paternal nucleus such as DNA lesions (breaks, deletions, mutations, ...) or numerical chromosome anomalies. More recently, male infertility has also been associated with changes in the sperm epigenome, including modification in the topology of chromatin (Olszewska et al., Chromosome Research 16:875-890, 2008; Alladin et al., Syst Biol Reprod Med 59: 146-152, 2013) ref with number 1, 2. Indeed, the positioning of chromosomes in the sperm nucleus is nonrandom and defines chromosome territories (Champroux et al., Genes (Basel) 9:501, 2018) ref with number 3 whose optimal organization determines the success of embryonic development. In this context, the study of the spatial distribution of chromosomes in sperm cells could be relevant for clinical diagnosis. We describe here a in situ fluorescence hybridization (FISH) strategy coupled with a fluorescent immunocytochemistry approach followed by confocal analysis and reconstruction (2D/3D) as a powerful tool to analyze the location of chromosomes in the sperm nucleus using the mouse sperm as a model. Already, the two-dimensional (2D) analysis of FISH and immunofluorescence data reveal the location of chromosomes as well as the different markings on the spermatic nucleus. In addition, a good 3D rendering after Imaris software processing was obtained when Z-stacks of images were acquired over a defined volume (10 μm × 13 μm × 15 μm) with a sequential scanning mode to minimize bleed-through effects and avoid overlapping wavelengths.


Preclinical development of T-cell receptor-engineered T-cell therapy targeting the 5T4 tumor antigen on renal cell carcinoma.
5T4 (trophoblast glycoprotein, TPBG) is a transmembrane tumor antigen expressed on more than 90% of primary renal cell carcinomas (RCC) and a wide range of human carcinomas but not on most somatic adult tissues. The favorable expression pattern has encouraged the development and clinical testing of 5T4-targeted antibody and vaccine therapies. 5T4 also represents a compelling and unexplored target for T-cell receptor (TCR)-engineered T-cell therapy. Our group has previously isolated high-avidity CD8+ T-cell clones specific for an HLA-A2-restricted 5T4 epitope (residues 17-25; 5T4p17). In this report, targeted single-cell RNA sequencing was performed on 5T4p17-specific T-cell clones to sequence the highly variable complementarity-determining region 3 (CDR3) of T-cell receptor α chain (TRA) and β chain (TRB) genes. Full-length TRA and TRB sequences were cloned into lentiviral vectors and transduced into CD8+ T-cells from healthy donors. Redirected effector T-cell function against 5T4p17 was measured by cytotoxicity and cytokine release assays. Seven unique TRA-TRB pairs were identified. All seven TCRs exhibited high expression on CD8+ T-cells with transduction efficiencies from 59 to 89%. TCR-transduced CD8+ T-cells demonstrated redirected cytotoxicity and cytokine release in response to 5T4p17 on target-cells and killed 5T4+/HLA-A2+ kidney-, breast-, and colorectal-tumor cell lines as well as primary RCC tumor cells in vitro. TCR-transduced CD8+ T-cells also detected presentation of 5T4p17 in TAP1/2-deficient T2 target-cells. TCR-transduced T-cells redirected to recognize the 5T4p17 epitope from a broadly shared tumor antigen are of interest for future testing as a cellular immunotherapy strategy for HLA-A2+ subjects with 5T4+ tumors.


Complications of robotic surgery in pediatric urology: a single institution experience.
To report our analysis of complications on pediatric robotic urologic procedures. A retrospective review was performed for all robotic surgeries by pediatric urologists at a single pediatric institution, from the start of the robotic surgery program in February 2009 through February 2013. Data included patient demographics, intraoperative details, outcomes, and complications (Clavien system). The analysis included 136 patients. There were 10 different types of procedures performed by 3 pediatric urologists. There were no intraoperative complications, robotic malfunctions, conversions to open or laparoscopic surgery, or mortalities. There were 11 total complications (8.1%): 2 grade I (1.5%), 7 grade II (5.1%), and 2 grade IIIb (1.5%). Complications included ileus in 2 patients (1.5%), port site infection in 2 (1.5%), urinary leak in 2 (1.5%), urinary retention in 2 (1.5%), urinary tract infection in 2 (1.5%), and stent migration in 1 (0.7%). The complication rate was in 3 of 10 infants (30%) and 8 of 126 noninfants (6.3%), P = .035. However, grade I, II, and IIIb complication rates were not significantly higher in infants vs noninfants, P = 1, .084, and .142, respectively. There was no difference in complication rates between the 3 surgeons. Pediatric robotic urologic procedures are safely performed with a relatively low complication rate and a low incidence of additional interventions owing to complications. Ongoing use of robotic technology in the pediatric population can be supported. Further reports are needed to validate our findings.


Theory for modeling the copolymerization of tubulin and tubulin-colchicine complex.
Substoichiometric concentrations of tubulin-colchicine complex (TC) inhibits microtubule assembly through a copolymerization reaction between tubulin and TC. We have determined the rates and extent of TC incorporation into bovine brain microtubules and developed a theory that models copolymerization. Our analysis suggests that while the apparent association rate constants for tubulin and TC are similar, the apparent dissociation rate constants for TC are a factor of five or more larger than those of tubulin. Copolymer composition showed only slight changes during assembly despite changes in the solution phase and showed little dependence at high TC upon the initial tubulin concentration. The theory was based on coupled Oosawa-Kasai equations that allow for the co-assembly of two components, tubulin and TC. An expression was derived that relates copolymer composition to reaction mixture composition and to the affinity of microtubule ends for tubulin and TC. This expression predicts copolymer composition at TC concentrations less than 10 microM and correlates composition with assembly inhibition. We perceive copolymerization as a facilitated incorporation of TC requiring the presence of tubulin. TC incorporation was dependent on the ratio of total tubulin to the dissociation constant for TC bound to microtubule ends. The copolymerization reaction is thus characterized by an interplay of two effects (a) where tubulin facilitates the incorporation of TC into the microtubule, and (b) where TC inhibits the assembly of tubulin into microtubules.


The clinical significance of metabolic syndrome in hypertension: metabolic syndrome increases cardiovascular risk : the contrary position.
From what is reported in the current literature, the 'metabolic syndrome' is believed to exist and flourish. Most also believe that the metabolic syndrome confers a cardiovascular risk well above the risk attributable to each of its components that are present at a certain time in a specific patient. Is this true and, specifically, is this true in hypertensive patients? Even the definition and the 'diagnosis' of metabolic syndrome are still under debate and very little is known about the average hypertensive patient who is often at high cardiovascular risk. Essential hypertension itself is a complex condition that involves the cardiovascular system, but has deep roots in metabolism and excessive adiposity, especially visceral, intra-abdominal adiposity. Non-optimal blood pressure and hypertension are likely to be the real 'vasculometabolic' syndrome that affects most humans, with the rare exceptions to be found in no-salt, no-fat cultures.


Locally Advanced Breast Cancer: Response Evaluation to Neoadjuvant Chemotherapy by Clinico-Histopathological Parameters and Molecular Imaging.
In India, breast cancer (BC) is not only the commonest cancer but also the commonest cause of cancer mortality among females. Advanced BC constitutes >70% of BC cases at initial presentation in India, among which locally advanced breast cancer (LABC) requires a multi-disciplinary approach with a combination of systemic and locoregional therapies. This descriptive hospital-based study was conducted over 1½ years after seeking approval from the institutional ethics committee. Fifty-five patients satisfying all the criteria of the study were enrolled. The data, thus, collected was pooled into Excel spreadsheet and analyzed using appropriate statistical tools. Most of the patients were postmenopausal, multiparous with breast lump being the commonest symptom. Mean baseline characteristics were age - 48 years, SUV max - 9.2, and Ki-67 - 17.8%. cT4 and cN2 were the commonest pre-NACT tumor and lymph node stage. Invasive ductal carcinoma was the commonest tumor type with the most common tumor grade being grade 3. Hormone receptor positivity and HER2 overexpression were seen in 33 and 17 patients respectively. Post-NACT 32 patients underwent breast-conserving surgery. Pathological complete response (pCR), i.e., ypT0N0, was seen in 13 patients (23.6%). There was slight alteration in hormone receptor status, HER2 expression and Ki-67 in the post-NACT resected tumor. pCR, which is a surrogate marker for improved clinical outcome (DFS and OS) in LABC patients, occurred more commonly in patients with pre-NACT grade 3 tumors, high Ki-67, hormone receptor-negative, and HER2 overexpressing BC (overall, in triple negative BC) but was statistically significant only with Ki-67. Post-NACT, SUV max with a cut off ≤1.5, and ΔSUV max of >80% correlated closely with pCR.


Purification and partial characterization of fructosyltransferase and invertase from Aspergillus niger AS0023.
Fructosyltransferase (EC.188.8.131.52) and invertase (EC.220.127.116.11) have been purified from the crude extract of Aspergillus niger AS0023 by successive chromatographies on DEAE-sephadex A-25, sepharose 6B, sephacryl S-200, and concanavalin A-Sepharose 4B columns. On acrylamide electrophoresis the two enzymes, in native and denatured forms, gave diffused glycoprotein bands with different electrophoretic mobility. On native-PAGE and SDS-PAGE, both enzymes migrated as polydisperse aggregates yielding broad and diffused bands. This result is typical of heterogeneous glycoproteins and the two enzymes have proved their glycoprotein nature by their adsorption on concanavalin A lectin. Fructosyltransferase (FTS) on native PAGE migrated as two enzymatically active bands with different electrophoretic mobility, one around 600 kDa and the other from 193 to 425 kDa. On SDS-PAGE, these two fractions yielded one band corresponding to a molecular weight range from 81 to 168 kDa. FTS seems to undergo association-dissociation of its glycoprotein subunits to form oligomers with different degrees of polymerization. Invertase (INV) showed higher mobility corresponding to a molecular range from 82 to 251 kDa, on native PAGE, and from 71 to 111 kDa on SDS-PAGE. The two enzymes exhibited distinctly different pH and temperature profiles. The optimum pH and temperature for FTS were found to be 5.8 and 50 degrees C, respectively, while INV showed optimum activity at pH 4.4 and 55 degrees C. Metal ions and other inhibitors had different effects on the two enzyme activities. FTS was completely abolished with 1 mM Hg(2+) and Ag(2+), while INV maintained 72 and 66% of its original activity, respectively. Furthermore, the two enzymes exhibited distinctly different kinetic constants confirming their different nature. The K(m) and V(m) values for each enzyme were calculated to be 44.38 mM and 1030 micromol ml(-1)min(-1) for FTS and 35.67 mM and 398 micromol ml(-1) min(-1) for INV, respectively. FTS and INV catalytic activity was dependent on sucrose concentration. FTS activity increased with increasing sucrose concentrations, while INV activity decreased markedly with increasing sucrose concentration. Furthermore, INV exhibited only hydrolytic activity producing exclusively fructose and glucose from sucrose, while FTS catalyzed exclusively fructosyltransfer reaction producing glucose, 1-kestose, nystose and fructofuranosyl nystose. In addition, at 50% sucrose concentration FTS produced fructooligosaccharides at the yield of 62% against 54% with the crude extract.


Hyperthyroidism during pregnancy treated with propylthiouracil. The significance of maternal and foetal parameters.
Hyperthyroidism during pregnancy may be dangerous to the infant. The major risks are prematurity and neonatal thyrotoxicosis. The latter may be due to placental transfer of thyroid stimulating immunoglobulins from mother to fetus. Of two siblings of a previously thyrotoxic mother the first had marked symptoms of neonatal thyrotoxicosis after a pregnancy where no antithyroid treatment was given. The second child had only minimal thyrotoxic symptoms but almost as high levels of thyroid hormones as the first. During the second pregnancy propylthiouracil was given to the mother from 26 weeks' gestation, because of increased fetal movements and fetal tachycardia. Fetal movements and fetal heart rate were considered to be most valuable indicators of thyroid function in the fetus. Intense control is necessary from the beginning of the second trimester.


Retrograde nephrostomy tube placement during open surgical procedures requiring urinary diversion.
A new nephrostomy tube has been designed that allows for atraumatic passage by a stylet from inside the renal pelvis through the renal cortex. The technique for safe insertion is described.


EGFR-TKI resistance promotes immune escape in lung cancer via increased PD-L1 expression.
The ATLANTIC trial reported that higher PD-L1 expression in tumors was involved in a higher objective response in patients with EGFR+/ALK+ non-small cell lung cancer (NSCLC), indicating the possibility of anti-PD-1/PD-L1 therapy as a third-line (or later) treatment for advanced NSCLC. Therefore, the determination of status and regulatory mechanisms of PD-L1 in EGFR mutant NSCLC before and after acquired EGFR-TKIs resistance are meaningful. The correlation among PD-L1, c-MET, and HGF was analyzed based on TCGA datasheets and paired NSCLC specimens before and after acquired EGFR-TKI resistance. EGFR-TKI resistant NSCLC cells with three well-known mechanisms, c-MET amplification, hepatocyte growth factor (HGF), and EGFR-T790M, were investigated to determinate PD-L1 expression status and immune escape ability. PD-L1-deleted EGFR-TKIs sensitive and resistant cells were used to evaluate the immune escape ability of tumors in mice xenograft models. Positive correlations were found among PD-L1, c-MET, and HGF, based on TCGA datasheets and paired NSCLC specimens. Moreover, the above three resistant mechanisms increased PD-L1 expression and attenuated activation and cytotoxicity of lymphocytes in vitro and in vivo, and downregulation of PD-L1 partially restored the cytotoxicity of lymphocytes. Both MAPK and PI3K pathways were involved in the three types of resistance mechanism-induced PD-L1 overexpression, whereas the NF-kappa B pathway was only involved in T790M-induced PD-L1 expression. HGF, MET-amplification, and EGFR-T790M upregulate PD-L1 expression in NSCLC and promote the immune escape of tumor cells through different mechanisms.


Gas reduction of intussusception.
Efforts to improve the non-surgical management of childhood intussusception centre around (a) reassessment of selection criteria used to ensure as many children as possible have the advantage of hydrostatic reduction, and (b) improvements and modifications of enema technique to ensure successful and safe reductions without increased morbidity. Reports that pneumatic reduction was highly successful in treating childhood intussusception prompted the authors to evaluate this technique over an 18 month period using our previously reported technique of oxygen at 2 litres/minute and a pressure of 80 mm Hg. Pneumatic reduction was attempted in 114 of 129 consecutive cases of intussusception, and was successful in 85 (75%). Fifteen patients (8.6%) were considered unacceptable risks for gas reduction using our current selection criteria and had primary surgery. The overall success rate considering all cases of intussusception managed at our institution over this period was 66% (85/129). As with any form of hydrostatic reduction, pneumatic reduction of intussusception requires careful selection of patients, meticulous technique, and awareness of complications and their appropriate management. Because of its simplicity and improved success rate, pneumatic reduction has replaced traditional barium reduction at our institution. It may be that with further evaluation of selection criteria, higher pressures, and prolonged attempts that results will improve further.


Presence of an endo-beta-galactosidase degrading the linkage region between the chondroitin sulfate chain and core peptide of proteoglycan.
Pyridylamino chondroitin sulfate, of which the reducing terminal xylose was coupled with a fluorescent 2-aminopyridine, was incubated at pH 4.0 with an extract from the mid-gut gland of Patnopecten. The high- and low-molecular-weight products were separated by ethanol precipitation, and identified by high-performance liquid chromatography analysis. The enzyme was found to expose a galactose residue at the reducing terminus of chondroitin sulfate, and also released the pyridylamino disaccharide, galactosylxylose, from the reducing terminal site of pyridylamino chondroitin sulfate. These results suggest that endo-beta-galactosidase activity, which hydrolyzes the galactosylgalactose linkage of peptidochondroitin sulfate, is present in the mid-gut gland of Patnopecten.


[Correlation between gene expression of CCK-A receptor and gallbladder emptying in gallstone patients].
To investigate the expression of CCK-A receptor and its relation with gallbladder hypomotility in patients with gallstone. 20 patients with gallstone and 10 normal subjects were studied and gallbladder emptying function was measured by B ultrasonography. The other 8 patients without gallstone who died of accident were selected as controls for measuring mRNA expression of CCK-A receptor of gallbladder; RT-PCR was used to explore gene expression of CCK-A receptor of gallbladder. The gallbladder motility was significantly impaired in gallstone patients. The patients had lower mRNA expression of CCK-A receptor than control subjects (0.633 +/- 0.167 vs. 0.944 +/- 0.230, P < 0.01), and so did patients with impaired gallbladder motility then those with normal motility (0.544 +/- 0.124 vs. 0.768 +/- 0.131, P < 0.05). Furthermore, the change of expression of CCK-A receptors was markedly correlated with gallbladder emptying (r = 0.925, P < 0.01). mRNA expression of CCK-A receptor in gallstone patients decreases, which was related to gallbladder hypomotility. The down-regulation of gene expression of CCK-A receptor plays an important role in gallbladder hypomotility in patients with gallstone.


Functionalized phosphorylated cellulose microspheres: Design, characterization and ciprofloxacin loading and releasing properties.
In this work, functionalized phosphorylated cellulose microspheres (CMP) were designed as a carrier for the ciprofloxacin (CIP) drug delivery system. The CMP has been developed from cellulose microspheres (CM) and phosphoric acid via an esterification reaction. CIP, an antibiotic drug as a model, was loaded onto CIP via hydrogen bonds and electrostatic interactions. A series of test results showed that the CIP was successfully incorporated and released from the prepared CMP without the loss of structural integrity or changing its functionality. The release kinetics and mechanism suggest that CIP release follows first-order kinetics and non-Fickian diffusion mechanism. The cytotoxicity behavior of CMP enables the material as a suitable vehicle for the safe release of CIP. The CIP loaded microspheres exhibited a significant antibacterial effect due to the CIP release and diffusion from the microspheres. This study provides insight into the design of suitable cellulose microspheres for CIP delivery.


Inhibitory activity and mechanism of inhibition of the N-[[(4-benzoylamino)phenyl]sulfonyl]amino acid aldose reductase inhibitors.
A series of substituted N-[[(4-benzoylamino)phenyl]sulfonyl]amino acids (BAPS-amino acids) were synthesized by established methods, and the stereochemistry of the products was confirmed by HPLC analysis after chiral derivatization. When tested against aldose reductase (alditol:NADP+ oxidoreductase; EC 184.108.40.206; ALR2) isolated from rat lens, all of the BAPS-amino acids were determined to be significantly more inhibitory than the corresponding N-(phenylsulfonyl)amino acids. Structure-inhibition and enzyme kinetic analyses suggest that the BAPS-amino acids inhibit ALR2 by a mechanism similar to the N-(phenylsulfonyl)amino acids. However, multiple inhibition analyses indicate that the increased inhibitory activity of the BAPS-amino acids is a result of interaction with multiple sites present on ALR2. Enzyme specificity studies with several of the BAPS-amino acids demonstrated that these compounds do not produce significant inhibition of other nucleotide-requiring enzymes including aldehyde reductase (alcohol: NADP+ oxidoreductase; EC 220.127.116.11; ALR1).


Identification of the Niemann-Pick C1-like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor.
Hepatitis C virus (HCV) is a leading cause of liver disease worldwide. With ∼170 million individuals infected and current interferon-based treatment having toxic side effects and marginal efficacy, more effective antivirals are crucially needed. Although HCV protease inhibitors were just approved by the US Food and Drug Administration (FDA), optimal HCV therapy, analogous to HIV therapy, will probably require a combination of antivirals targeting multiple aspects of the viral lifecycle. Viral entry represents a potential multifaceted target for antiviral intervention; however, to date, FDA-approved inhibitors of HCV cell entry are unavailable. Here we show that the cellular Niemann-Pick C1-like 1 (NPC1L1) cholesterol uptake receptor is an HCV entry factor amendable to therapeutic intervention. Specifically, NPC1L1 expression is necessary for HCV infection, as silencing or antibody-mediated blocking of NPC1L1 impairs cell culture-derived HCV (HCVcc) infection initiation. In addition, the clinically available FDA-approved NPC1L1 antagonist ezetimibe potently blocks HCV uptake in vitro via a virion cholesterol-dependent step before virion-cell membrane fusion. Moreover, ezetimibe inhibits infection by all major HCV genotypes in vitro and in vivo delays the establishment of HCV genotype 1b infection in mice with human liver grafts. Thus, we have not only identified NPC1L1 as an HCV cell entry factor but also discovered a new antiviral target and potential therapeutic agent.


Synthesis of Bis(1,2,3-Triazole) Functionalized Quinoline-2,4-Diones.
Derivatives of 3-(1H-1,2,3-triazol-1-yl)quinoline-2,4(1H,3H)-dione unsubstituted on quinolone nitrogen atom, which are available by the previously described four step synthesis starting from aniline, were exploited as intermediates in obtaining the title compounds. The procedure involves the introduction of propargyl group onto the quinolone nitrogen atom of mentioned intermediates by the reaction of them with propargyl bromide in N,N-dimethylformamide (DMF) in presence of a potassium carbonate and the subsequent formation of a second triazole ring by copper catalyzed cyclisation reaction with azido compounds. The products were characterized by ¹H, 13C and 15N NMR spectroscopy. The corresponding resonances were assigned on the basis of the standard 1D and gradient selected 2D NMR experiments (¹H⁻¹H gs-COSY, ¹H⁻13C gs-HSQC, ¹H⁻13C gs-HMBC) with ¹H⁻15N gs-HMBC as a practical tool to determine 15N NMR chemical shifts at the natural abundance level of 15N isotope.


Two confirmatory tests for identification of Neisseria gonorrhoeae from primary culture.
We compared a fluorescent monoclonal antibody and a DNA probe for identification of Neisseria gonorrhoeae (GC) from primary genital cultures of presumptive GC and selected bacterial isolates other than GC. The monoclonal antibody was sensitive (94%) and specific (100%) enough to identify GC in selective primary genital culture. The DNA probe was sensitive (95%) but not adequately specific (65%) to function as a confirmatory test.


Ecosystem consequences of species richness and composition in pond food webs.
Resolving current concerns about the role of biodiversity on ecosystems calls for understanding the separate roles of changes in species numbers and of composition. Recent work shows that primary productivity often, but not always, saturates with species richness within single trophic levels. However, any interpretation of such patterns must consider that variation in biodiversity is necessarily associated with changes in species composition (identity), and that changes in biodiversity often occur across multiple trophic levels. Here we present results from a mesocosm experiment in which we independently manipulated species richness and species composition across multiple trophic levels in pond food webs. In contrast to previous studies that focused on single trophic levels, we found that productivity is either idiosyncratic or increases with respect to species richness, and that richness influences trophic structure. However, the composition of species within richness levels can have equally or more marked effects on ecosystems than average effects of richness per se. Indirect evidence suggests that richness and associated changes in species composition affect ecosystem attributes through indirect effects and trophic interactions among species, features that are highly characteristic of natural, complex ecosystems.


Oral hygiene associated with antimicrobial photodynamic therapy or lingual scraper in the reduction of halitosis after 90 days follow up: A randomized, controlled, single-blinded trial.
Although antimicrobial photodynamic therapy (aPDT) can reduce halitosis immediately after application, it returns after a week. This probably occurs because bacteria residing in the oral cavity may recolonize the dorsum of the tongue. Verify if modification of oral hygiene behavior associated with aPDT or lingual scraper can reduce halitosis after a 90-day follow-up. Forty adults with positive halitosis were randomized in G1 (n = 20) -aPDT + oral hygiene behavior (OHB) or G2 (n = 20)- lingual scraper + OHB. G1 group were submitted to 0.005 % methylene blue in the middle and posterior third of the tongue, with pre-irradiation of 1 min. Irradiations were performed with red laser diode (λ =660 nm), 100 mW, 318 J/cm2, 3537 mW/cm2, 9 J per point at 6 points. In the G2 group, the tongue was scraped 10 times on the right side and on the left side with a tongue scraper. All patients were instructed on OHB at baseline, 7 and 90 days (guidance on the use of dental floss and the Bass technique for brushing). Halitosis was evaluated by gas chromatography (OralChroma®). Values > 112 ppb for Hydrogen sulfide (H2S) gas was considered positive halitosis. Methylmercaptanes and dimethylsulfide were also measured. The gas measures were assessed at baseline, immediately, and at 7 and 90 days. Paired t-test was used for the statistical analysis. For comparison between groups, the t-test was used. Values of p < 0.05 were considered statistically significant. There was no difference between groups immediately after treatment (p = .1532) after 7 days (p = 0.9312) and 90 days (p = 0.6642). For the aPDT group, there was a decrease in hydrogen sulfide immediately after treatment (p = 0.0001), after 7 days, values remained 3-fold smaller (p = 0.0088) and 2-fold smaller after 90 days (p = 0.0270). For the scraper group, there was a decrease immediately after treatment (p = 0.0001), the values remains 2-fold smaller (p = 0.0003) after 7 days and 3 months (p = 0.0001). The oral hygiene behavior associated with aPDT or tongue scraper was not able to reduce halitosis after 90-day follow-up. Despite halitosis remaining  higher than 112 ppb in all follow-up periods, the mean values remain 2 or 3 fold smaller than baseline values. Future studies should include other oral hygiene behavior to achieve better results in the treatment of halitosis.


Neck shrivel in European plum is caused by cuticular microcracks, resulting from rapid lateral expansion of the neck late in development.
Susceptibility to neck shrivel in European plum is due to cuticular microcracking resulting from high surface area growth rates in the neck region, late in development. Susceptibility to the commercially important fruit disorder 'neck shrivel' differs among European plum cultivars. Radial cuticular microcracking occurs in the neck regions of susceptible cultivars, but not in non-susceptible ones, so would seem to be causal. However, the reason for the microcracking is unknown. The objective was to identify potential relationships between fruit growth pattern and microcracking incidence in the neck (proximal) and stylar (distal) ends of selected shrivel-susceptible and non-susceptible cultivars. Growth analysis revealed two allometric categories: The first category, the 'narrow-neck' cultivars, showed hypoallometric growth in the neck region (i.e., slower growth than in the region of maximum diameter) during early development (stages I + II). Later (during stage III) the neck region was 'filled out' by hyperallometric growth (i.e., faster than in the region of maximum diameter). The second category, the 'broad-neck' cultivars, had more symmetrical, allometric growth (all regions grew equally fast) throughout development. The narrow-neck cultivars exhibited extensive radial cuticular microcracking in the neck region, but little microcracking in the stylar region. In contrast, the broad-neck cultivars exhibited little microcracking overall, with no difference between the neck and stylar regions. Across all cultivars, a positive relationship was obtained for the level of microcracking in the neck region and the difference in allometric growth ratios between stage III and stages I + II. There were no similar relationships for the stylar region. The results demonstrate that accelerated stage III neck growth in the narrow-neck plum cultivars is associated with more microcracking and thus with more shrivel.


Isolation and characterization of a novel lectin from the wild mushroom Xerocomus spadiceus.
A lectin was isolated from extracts of fruiting bodies of the mushroom Xerocomus spadiceus using a procedure that involved ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, ion exchange chromatography on CM-cellulose, and gel filtration by fast protein liquid chromatography on Superdex 75. The lectin was unadsorbed on DEAE-cellulose and Affi-gel blue gel and adsorbed on CM-Sepharose. The lectin was capable of eliciting an approximately four-fold stimulation of mitogenic response in murine splenocytes. The hemagglutinating activity was stable up to 60 degrees C, halved at 70 degrees C, reduced to 25% at 75 degrees C and dwindled to an undetectable level at 80 degrees C. The activity remained unaltered in the presence of various divalent (Ca2+, Mg2+, Zn2+ and Mn2+) chlorides up to a salt concentration of 10 mM except in the case of ZnCl2. FeCl3 up to a concentration of 10 mM did not affect the hemagglutinating activity of the lectin. The hemagglutinating activity of the lectin was doubled in the presence of 5 mM AlCl3 or 10 mM ZnCl2 and quadrupled in the presence of 10 mM AlCl3. The activity was reduced in the presence of HCl and NaOH. Among the large number of carbohydrates tested, only inulin was able to inhibit the hemagglutinating activity of the lectin.


Radiation pneumonitis prediction after stereotactic body radiation therapy based on 3D dose distribution: dosiomics and/or deep learning-based radiomics features.
This study was designed to establish radiation pneumonitis (RP) prediction models using dosiomics and/or deep learning-based radiomics (DLR) features based on 3D dose distribution. A total of 140 patients with non-small cell lung cancer who received stereotactic body radiation therapy (SBRT) were retrospectively included in this study. These patients were randomly divided into the training (n = 112) and test (n = 28) sets. Besides, 107 dosiomics features were extracted by Pyradiomics, and 1316 DLR features were extracted by ResNet50. Feature visualization was performed based on Spearman's correlation coefficients, and feature selection was performed based on the least absolute shrinkage and selection operator. Three different models were constructed based on random forest, including (1) a dosiomics model (a model constructed based on dosiomics features), (2) a DLR model (a model constructed based on DLR features), and (3) a hybrid model (a model constructed based on dosiomics and DLR features). Subsequently, the performance of these three models was compared with receiver operating characteristic curves. Finally, these dosiomics and DLR features were analyzed with Spearman's correlation coefficients. In the training set, the area under the curve (AUC) of the dosiomics, DLR, and hybrid models was 0.9986, 0.9992, and 0.9993, respectively; the accuracy of these three models was 0.9643, 0.9464, and 0.9642, respectively. In the test set, the AUC of these three models was 0.8462, 0.8750, and 0.9000, respectively; the accuracy of these three models was 0.8214, 0.7857, and 0.8571, respectively. The hybrid model based on dosiomics and DLR features outperformed other two models. Correlation analysis between dosiomics features and DLR features showed weak correlations. The dosiomics features that correlated DLR features with the Spearman's rho |ρ| ≥ 0.8 were all first-order features. The hybrid features based on dosiomics and DLR features from 3D dose distribution could improve the performance of RP prediction after SBRT.


Early postoperative recovery of idiopathic macular hole in a young adult.
Idiopathic macular holes usually develop in the elderly. We report the case of a spontaneous macular hole in a 23-year-old man. The patient noticed decreased central vision in his left eye since 5 days without any history of trauma or intraocular inflammation. On examination the best corrected visual acuity was 20/20 in the right eye and 20/50 in the left. Fundus biomicroscopy and OCT showed a full-thickness macular hole. Microperimetry demonstrated a scotoma within the macular hole. 2 months later the patient underwent pars plana vitrectomy, ILM-peeling with trypan blue staining and fluid-air exchange followed by face down positioning for 12 h a day for 2 days. On the 4th post-surgical day visual acuity was 20/32 and OCT showed a complete closure of the macular hole. During the further follow-up visual acuity in the left eye improved to 20/20. OCT examination showed a restored foveal depression, and microperimetry demonstrated an increased foveal sensitivity in the area of the previous scotoma. The aetiology of the macular hole in this patient is unclear. It is most likely an idiopathic macular hole in a young person. Post-surgical follow-up OCTs and microperimetry disclosed an early recovery of the foveal anatomy and function.


Reduction of intercellular adhesion molecule 1 may play a role in anti-inflammatory effect of hyaluronic acid in a rat model of severe non-bacterial cystitis.
To evaluate the impact of intercellular adhesion molecule 1 (ICAM-1) in hyaluronic acid (HA) therapy in rats model of severe non-bacterial cystitis. Cystitis models in Sprague-Dawley female rats were produced by combination of intraperitoneal cyclophosphamide (CYP) with intravesical protamine/lipopolysaccharide (PS/LPS). HA or heparin (0.5 ml) was introduced intravesically to rats' bladders followed PS/LPS. Bladder tissue was prepared for histology including mast cell presence and measurement of ICAM-1, tumor necrosis factor (TNF)-α, and interleukin 6 (IL-6). Cystitis model using intraperitoneal CYP and intravesical SP/LPS showed serious inflammation, higher mast cell count with elevated ICAM-1, TNF-α, and IL-6 levels. After intravesical heparin or HA treatment, incidence of grades 3-4 bladder inflammation and tissue ICAM-1 level were only significantly lower in HA group (P = 0.017, P = 0.021, respectively), but not in heparin group (P = 0.12, P = 0.798, respectively). Remarkably lower level of TNF-α (P = 0.003) and ICAM-1 (P = 0.006) was detected in HA-treated rats compared with heparin-treated rats. Inflammation grade and ICAM-1 level had strong correlation (P < 0.001). IL-6 level after HA or heparin instillation had no difference. Intravesical administration of HA decreased the severity of bladder inflammation, mast cell presence, and levels of ICAM-1 and TNF-α in a rat model of severe non-bacterial cystitis; its effect was more obvious than that of heparin. Reduction of ICAM-1 may play a role in the anti-inflammatory effect of HA.


A ratiometric ESIPT fluorescent probe for detection of anticancer-associated H2O2 level in vitro and in vivo.
ROS is a significant factor in the cancer treatment mechanism. The monitoring anticancer-associated H2O2 level plays a vital role in the anticancer mechanistic exploration in pathology and physiology. Herein we synthesized a ratiometric fluorescent probe (HBQ-L) to detect and image H2O2 based on excited-state intramolecular proton transfer. HBQ-L had a high sensitivity (231-fold) with a low detection limit (28.5 nM) for monitoring H2O2 in solution. HBQ-L showed good mitochondrial-targeting and successfully detected both exo-/endogenous H2O2 in A549 cells. Furthermore, HBQ-L was used to ratiometric monitor H2O2 level in anticancer reagent DOX-treated cells or zebrafish. Importantly, it was employed to access the monitoring H2O2 in the A549 tumor-bearing mice.


Dental implants in patients with orofacial clefts: a long-term follow-up study.
Aim of this study was to determine the success of implants that were inserted in patients with cleft of the lip, alveolus and palate (CLAP) and to identify prognosis-relevant factors. In a prospective evaluation, 75 implants inserted in combination with bone grafting at cleft sites of 45 patients were examined. The observation period extended 5.5 years in average (minimum 1.5, maximum 11.3 years). Implant success was evaluated clinically and radiographically and was compared to age- and gender-matched control groups. Statistic assessment included Kaplan-Meier survival analysis, Log rank tests and Cox regression analysis. In total, 10 implants were lost in 8 patients, resulting in an implant survival rate of 82.2% at the end of the observation period. Patient-related parameters of age, gender or type of cleft had no significant influence. The length of an implant was significantly related to an improved survival rate (P<0.01). Implant survival was less in CLAP patients when compared to implant insertions in a non-cleft control group, but improved when compared to patients with bone grafting for other indications. It is concluded that implants combined with bone grafting can offer a reliable alternative in patients with CLAP.