Type of intruder and reproductive phase influence male territorial defence in wild-caught Siamese fighting fish.
This study investigated how parental care increases with offspring age by examining the level of male aggressiveness toward potential intruders during egg guarding in a natural population of Siamese fighting fish (Betta splendens Regan). The degree of aggressiveness was measured at two reproductive phases in response to three types of intruders: male, female and females that have laid eggs. The nest-holding males became more aggressive after their eggs hatched than after the eggs were laid. Nest-holding males displayed gill cover erection, biting, tail beating and attacking at the highest rate towards male intruders, intermediate towards female intruders and the least aggressive towards females, which have laid eggs.


Cutaneous manifestation of internal malignancies (I). Acanthosis nigricans.
Skin changes may be the first clue to a neoplastic process at a stage when it still is treatable (Such as the development of Acanthosis Nigrican (AN) in an otherwise healthy adult). Ninety percent of the neoplasm responsible for the development of AN originate in the abdomen. The tumor, even in a subclinical state, seems to possess unidentified properties that activate the dermatosis.


Heterakidosis and nodular granulomas caused by Heterakis isolonche in the ceca of gallinaceous birds.
Five pheasants and two ocellated turkeys from the San Diego Zoological Garden had multiple cecal nodules. These nodules were composed mostly of granulomas and fibrous hyperplastic tissue associated with Heterakis isolonche.


Endophytic fungi: a potential source for drugs against central nervous system disorders.
Neuroprotection is one of the important protection methods against neuronal cells and tissue damage caused by neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and multiple sclerosis. Various bioactive compounds produced by medicinal plants can potentially treat central nervous system (CNS) disorders. Apart from these resources, endophytes also produce diverse secondary metabolites capable of protecting the CNS. The bioactive compounds produced by endophytes play essential roles in enhancing the growth factors, antioxidant defence functions, diminishing neuroinflammatory, and apoptotic pathways. The efficacy of compounds produced by endophytic fungi was also evaluated by enzymes, cell lines, and in vivo models. Acetylcholine esterase (AChE) inhibition is frequently used to assess in vitro neuroprotective activity along with cytotoxicity-induced neuronal cell lines. Some of drugs, such as tacrine, donepezil, rivastigmine, galantamine, and other compounds, are generally used as reference standards. Furthermore, clinical trials are required to confirm the role of these natural compounds in neuroprotection efficacy and evaluate their safety profile. This review illustrates the production of various bioactive compounds produced by endophytic fungi and their role in preventing neurodegeneration.


The fatty acids of calcareous sponges (Calcarea, Porifera).
Twenty-nine specimens of calcareous sponges (Class Calcarea, Phylum Porifera), covering thirteen representative species of the families Soleneiscidae, Leucaltidae, Levinellidae, Leucettidae, Clathrinidae, Sycettidae, Grantiidae, Jenkinidae, and Heteropiidae were analysed for their fatty acids. The fatty acids of Calcarea generally comprise saturated and monounsaturated linear (n-), and terminally methylated (iso-, anteiso-) C(14)-C(20) homologues. Furthermore, polyunsaturated C(22) fatty acids and the isoprenoic 4,8,12-trimethyltridecanoic acid were found. The most prominent compounds are n-C(16), iso-C(17), iso-C(18), n-C(18), n-C(20). In addition, a high abundance of the exotic 16-methyloctadecanoic acid (anteiso-C(19)) appears to be a characteristic trait of Calcarea. Long-chain 'demospongic acids', typically found in Demospongiae and Hexactinellida, are absent in Calcarea. The completely different strategy of calcarean fatty acid synthesis supports their phylogenetic distinctiveness from a common Demospongiae/Hexactinellida taxon. Both intraspecific and intraclass patterns of Calcarea showed great similarity, suggesting a conserved fatty acid composition that already existed in the last common ancestor of Calcinea and Calcaronea, i.e. before subclasses diverged.


High-Throughput CRISPR-Cas13 SARS-CoV-2 Test.
The ability to control the spread of COVID-19 continues to be hampered by a lack of rapid, scalable, and easily deployable diagnostic solutions. We developed a diagnostic method based on CRISPR (clustered regularly interspaced short palindromic repeats) that can deliver sensitive, specific, and high-throughput detection of Sudden Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). The assay utilizes SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) for the qualitative detection of SARS-CoV-2 RNA and may be performed directly on a swab or saliva sample without nucleic acid extraction. The assay uses a 384-well format and provides results in <1 hour. Assay performance was evaluated with 105 (55 negative, 50 positive) remnant SARS-CoV-2 specimens previously tested using Food and Drug Administration emergency use authorized assays and retested with a modified version of the Centers for Disease Control and Prevention (CDC) quantitative PCR with reverse transcription (RT-qPCR) assay. When combined with magnetic bead-based extraction, the high-throughput SHERLOCK SARS-CoV-2 assay was 100% concordant (n = 60) with the CDC RT-qPCR. When used with direct sample addition the high-throughput assay was also 100% concordant with the CDC RT-qPCR direct method (n = 45). With direct saliva sample addition, the negative and positive percentage agreements were 100% (15/15, 95% CI: 81.8-100%) and 88% (15/17, 95% CI: 63.6-98.5%), respectively, compared with results from a collaborating clinical laboratory. This high-throughput assay identifies SARS-CoV-2 from patient samples with or without nucleic acid extraction with high concordance to RT-qPCR methods. This test enables high complexity laboratories to rapidly increase their testing capacities with simple equipment.


Not as simple as it seems: extensive facility and training gaps in nursing home bathing.
Standardized observation of bed baths and showers for 100 residents in 8 nursing homes revealed inadequate cleansing of body sites (88%-100% failure) and >90% process failure involving lather, firm massage, changing dirty wipes or cloths, and following clean-to-dirty sequence. Insufficient water warmth affected 86% of bathing opportunities. Bathing training and adequate resources are needed.


Depression and human immunodeficiency virus infection are risk factors for incident heart failure among veterans: Veterans Aging Cohort Study.
Both HIV and depression are associated with increased heart failure (HF) risk. Depression, a common comorbidity, may further increase the risk of HF among adults with HIV infection (HIV+). We assessed the association between HIV, depression, and incident HF. Veterans Aging Cohort Study (VACS) participants free from cardiovascular disease at baseline (n=81 427: 26 908 HIV+, 54 519 without HIV [HIV-]) were categorized into 4 groups: HIV- without major depressive disorder (MDD) [reference], HIV- with MDD, HIV+ without MDD, and HIV+ with MDD. International Classification of Diseases, Ninth Revision codes from medical records were used to determine MDD and the primary outcome, HF. After 5.8 years of follow-up, HF rates per 1000 person-years were highest among HIV+ participants with MDD (9.32; 95% confidence interval [CI], 8.20-10.6). In Cox proportional hazards models, HIV+ participants with MDD had a significantly higher risk of HF (adjusted hazard ratio, 1.68; 95% CI, 1.45-1.95) compared with HIV- participants without MDD. MDD was associated with HF in separate fully adjusted models for HIV- and HIV+ participants (adjusted hazard ratio, 1.21; 95% CI, 1.06-1.37; and adjusted hazard ratio, 1.29; 95% CI, 1.11-1.51, respectively). Among those with MDD, baseline antidepressant use was associated with lower risk of incident HF events (adjusted hazard ratio, 0.76; 95% CI, 0.58-0.99). Our study is the first to suggest that MDD is an independent risk factor for HF in HIV+ adults. These results reinforce the importance of identifying and managing MDD among HIV+ patients. Future studies must clarify mechanisms linking HIV, MDD, antidepressants, and HF and identify interventions to reduce HF morbidity and mortality in those with both HIV and MDD.


Risk Factors and Management of Hemodialysis Associated Distal Ischemia.
Hemodialysis-associated distal ischemia (HADI) is an uncommon, but significant complication after hemodialysis access creation that might require additional intervention. This study examines the risk factors for HADI and compares the outcomes of the different treatment modalities. The Vascular Quality Initiative hemodialysis access (2011-2019) registry was reviewed. Patients were classified based on the occurrence of HADI requiring intervention or not, and their respective characteristics were compared. Multivariable logistic regression was used to identify independent factors associated with HADI. Kaplan Meier curves of secondary patency after different modalities of surgical revision were compared. There were 35,236 vascular access creations and 970 (2.75%) were complicated by HADI requiring intervention. Treatment was performed with access ligation in 224 patients (23%) and catheter-based techniques in 394 (41%). Open surgical revision consisted of banding in 127 (13%), distal revascularization interval ligation (DRIL) in 196 (20%), proximalization of arterial inflow (PAI) in 15 (1.5%), and revision using distal inflow (RUDI) in 14 (1.4%). Median time to HADI was 49 days (IQR 17 -91 days). Multivariate regression demonstrated that white race, female sex, peripheral artery disease, coronary artery disease, diabetes, post-procedure antiplatelets, prosthetic grafts, upper arm access, and target vein diameter greater than 4 mm were significantly associated with increased risk for HADI. When compared to procedures without HADI, access patency was decreased when revision (excluding access ligation) was performed (secondary patency at 12 months, HADI revision versus none: 89.0% vs. 92.4%, P <0.01). However, after multivariate Cox adjustment, revision for HADI was not independently significantly associated with access failure. HADI complicates 2.75% of hemodialysis access cases and is more likely in white females with diabetes and arterial disease after upper arm prosthetic graft placement. The patency of dialysis access does not seem to be negatively impacted by the various methods of surgical revision for HADI.


MGMT promoter hypermethylation correlates with a survival benefit from temozolomide in patients with recurrent anaplastic astrocytoma but not glioblastoma.
To investigate the correlation between O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter methylation and benefit from temozolomide in patients with recurrent high-grade glioma. A real-time, quantitative, methylation-specific PCR assay was performed on archival tissue blocks from patients treated with temozolomide at the first recurrence. A subgroup of 38 patients who were chemotherapy-naive at recurrence was analysed (22 glioblastoma, 12 anaplastic astrocytoma [AA] and 4 anaplastic oligoastrocytoma [AOA]); none had 1p/19q loss. Among 10 (26%) patients with a hypermethylated MGMT promoter, none experienced disease progression within the first two treatment cycles compared with 12 of 28 (43%) patients with an unmethylated promoter (p=0.016). By Cox multivariate analysis, tumour grade and MGMT promoter methylation correlated with time to progression (p<0.05); MGMT promoter methylation correlated with superior overall survival in AA/AOA but not in glioblastoma. MGMT promoter methylation predicted a survival benefit in patients with 1p/19q intact AA/AOA treated with temozolomide at recurrence.


Interactions among phytophagous insect species colonizing cones of white fir (Abies concolor).
The insect complex colonizing white fir (Abies concolor [Gord. and Glend.] Lindl.) cones is composed of eleven species that can be separated into three feeding guilds: the seed-mining guild, Megastigmus pinus Parfitt, M. rafni Hoffmeyer, Earomyia abietum McAlpine; the cone-and seed-mining guild, Dioryctria abietivorella Grote, Eucosma prob. siskiyouana (Kearfoot), Cydia prob. bracteatana (Fernald), Barbara sp.; the scale-and bract-feeding guild, Asynapta hokinsi (Felt), Dasineura prob. abiesemia Foote, Ressiliella conicola (Foote), Lasiomma abietis Huckett). In three of four study sites the cone crop decreased from one year to the next. As cone crop size decreased there was a concomitant increase in the percent of cones with more than one species. In addition, there was a shift toward an increased co-occurrence of members of different guilds within a single cone. Both positive and negative interactions were detected between selected species-pairs. Present-day competition was only inferred between species-pairs belonging to the cone and seed-mining guild. Decreasing resources over time, combined with increasing insect populations and the absence of acceptable alternate hosts appeared to be important factors for setting conditions conducive to interspecific competition. It is hypothesized, that the aperiodicity of white fir cone crops was important in keeping insect populations below levels which would result in interspecific competition. The possible elimination of aperiodicity in cone crops of white fir, such as might occur in managed seed orchards, may lead to decreased species diversity via competitive exclusion and thereby simplify development of IPM programs.


The necessity for an integrated Emergency Operations Center (EOC) among first responders: Lesson learned from two Iranian railway accidents.
Several train accidents have occurred in Iran in the last twenty years, resulting in considerable loss of human lives. This study aims to investigate and analyze the response process and deficiencies thereof, of three responding organizations to two railway accidents in Iran. The study was performed in 2 stages to examine the challenges faced by the first responders in the said accidents. In the first stage, a descriptive statistical analysis was conducted to estimate the injuries and loss of human lives. In the second stage, qualitative description (QD) was performed. Technical reports, official documents, and interviews contributed to the sources of primary data. Study participants were members of first responders who were interviewed. The lack of key components like coordination, information-sharing, a single unified command between responders from different organizations, a lack of relief and rescue railway train, and poor inter-organizational interactions in the deployment of relief teams, were found to be the most important challenges. The analysis of these two accidents showed that the lack of an integrated emergency operations center (EOC) among the organizations involved in the emergency response appears to be the obvious cause of initial confusion and disruption in the response phase which caused a delay which proved fatal. Designing and developing an integrated response plan among responding organizations, preparing an information sharing network, centralized deployment of forces to the site of the accident, strengthening inter-organizational interactions in the form of an incident command system, designing, launching, and using rescue trains on rail routes and use of air emergency facilities in areas with poor accessibility can reduce mortality in future in similar kind of accidents.


Mapping of the tobacco vein mottling virus VPg cistron.
The location of the cistron encoding the genome-linked protein (VPg) in the potyvirus tobacco vein mottling virus (TVMV) was investigated. Precipitation of 125I-labeled VPg with anti-tobacco etch virus 49K nuclear inclusion protein antiserum (which reacts with the NIa nuclear inclusion protein of TVMV) indicated that the TVMV VPg is immunologically related to NIa. Lysyl residues were found to be present at positions 2, 11, and 16 of the amino-terminal region of the VPg. A search of the TVMV polyprotein sequence for this distribution of lysyl residues revealed a unique location beginning at amino acid residue 1801, the proposed amino-terminus of the NIa protein.


Experimental muscular amebiasis in hamsters as a biological model.
Trophozoites of Entamoeba histolytica maintained in vitro in Pavlova's medium were inoculated by deep intramuscular injection into the proximal left hindleg of hamsters. Thioglycollate medium was utilized as a successful vehicle to induce the infection. The invasion of the muscular tissue by the vegetative forms caused the formation of abscesses with great destruction of muscular fibers. The lesions were limited to the muscular tissue of the femoral area. The number of trophozoites, the medium of thioglycollate as a vehicle, the volume of the inoculum and the trauma caused by the needle were important elements in the evolution of the muscular amebic abscesses. A limited trial of the amebicidal activity of metronidazole utilizing the amebic intramuscular infection was also performed.


Scorecards and dashboards: using financial metrics to improve performance.
To develop a dashboard reporting system for hospitals, four critical factors should be taken into account: Factors most important to the organization's success. Critical drivers that influence performance attainment. Relevant measures. Relevant benchmarking data.


Continuing Need for Sexually Transmitted Disease Clinics After the Affordable Care Act.
We assessed the characteristics of sexually transmitted disease (STD) clinic patients, their reasons for seeking health services in STD clinics, and their access to health care in other venues. In 2013, we surveyed persons who used publicly funded STD clinics in 21 US cities with the highest STD morbidity. Of the 4364 STD clinic patients we surveyed, 58.5% were younger than 30 years, 72.5% were non-White, and 49.9% were uninsured. They visited the clinic for STD symptoms (18.9%), STD screening (33.8%), and HIV testing (13.6%). Patients chose STD clinics because of walk-in, same-day appointments (49.5%), low cost (23.9%), and expert care (8.3%). Among STD clinic patients, 60.4% had access to another type of venue for sick care, and 58.5% had access to another type of venue for preventive care. Most insured patients (51.6%) were willing to use insurance to pay for care at the STD clinic. Despite access to other health care settings, patients chose STD clinics for sexual health care because of convenient, low-cost, and expert care. Policy Implication. STD clinics play an important role in STD prevention by offering walk-in care to uninsured patients.


Prognostic value of pentraxin-3 level in patients with STEMI and its relationship with heart failure and markers of oxidative stress.
Pentraxin-3 (PTX3) appears to have a cardioprotective effect through a positive influence against postreperfusion damage. This study assesses the prognostic value of PTX3 level and its relationship with clinical parameters and markers of oxidative stress and nitric oxide metabolism in patients with ST-elevation myocardial infarction (STEMI). Plasma/serum levels of several biomarkers of inflammation and oxidative stress and nitrite/nitrate were assessed upon admission and 24 h after STEMI onset in patients treated by primary percutaneous coronary intervention. ROC analysis showed that plasma PTX3 at 24 h was a strong predictor of 30-day and 1-year mortality and independent predictor of combined end-point of left ventricle dysfunction or mortality in 1 year. The inflammatory response expressed by PTX3 had a significant relationship with age, heart failure, infarct size, impaired flow in the infarct-related artery, and renal function and positively correlated with neopterin, TNF-α, 8-hydroxy-2'-deoxyguanosine, and nitrite/nitrate. Plasma PTX3 at 24 h after STEMI onset is a strong predictor of 30-day and 1-year mortality. PTX3 as a single biomarker is comparable with currently used scoring systems (TIMI or GRACE) or B-type natriuretic peptide. PTX3 is also an independent predictor of combined end-point of left ventricle dysfunction or mortality in 1 year.


Effects of blocking plasma lipid transfer protein activity in the rabbit.
Plasma lipid transfer protein activity was completely blocked in rabbits for up to 48 h by infusion with goat antibody to rabbit lipid transfer protein. Lipid transfer protein activity in plasma of control animals, infused with antibody from a non-immune goat, decreased during the experiment but was never less than 50% of pre-infusion levels. During the period that lipid transfer protein activity was completely blocked, there were changes in high-density lipoprotein composition (expressed as % by weight) with a reduction in triacylglycerol from 8.4 +/- 2.4% to 1.0 +/- 0.2% (P less than 0.05) and an increase in esterified cholesterol from 10.7 +/- 1.7% to 14.5 +/- 0.3% (P less than 0.1). In conjunction with the observed changes in high-density lipoprotein composition, there was an increase in high-density lipoprotein particle size from a mean radius of 4.7 to 5.4 nm. The change in composition and particle size was not observed in high-density lipoproteins from control animals. There was a change in the distribution of plasma cholesterol in control animals, with a fall in the proportion of cholesterol in high-density lipoproteins (P less than 0.02) and consequently an increase in the proportion of cholesterol in low-density lipoproteins (P less than 0.02). However, the distribution of plasma cholesterol in animals in which lipid transfer protein activity was inhibited was maintained at original levels during the period of inhibition. Consequently, in these animals, there was a less atherogenic distribution of cholesterol during the period of lipid transfer protein inhibition when compared with control animals. The changes observed in lipoproteins, in the absence of lipid transfer protein activity, demonstrate that lipid transfer protein modifies lipoproteins in vivo and appears to contribute to a more atherogenic lipid profile.


A case of anti-nuclear antibody negative systemic lupus erythematosus associated with penile ulcer.
We report here an old male patient with anti-nuclear antibody (ANA) negative systemic lupus erythematosus (SLE) with active renal disease and penile ulcer. He revealed nephrotic syndrome, malar rash and oral ulcer. SLE was discussed, however both ANA and anti-DNA antibody were persistently negative. A penile ulcer was also observed. He died of acute respiratory distress. Autopsy findings including onion skin lesion in the spleen and haematoxylin body in the kidney resulted in the final diagnosis of SLE. To our knowledge, association of penile ulcer with SLE has not yet been reported. Therefore, the present case is thought to be extremely unusual.


T (Thomsen-Friedenreich) and Tn epitope location and their spatial relations to adhesion plaques on human breast carcinoma cells: immunogold-silver staining studies at scanning electron microscopic level.
T and Tn are pancarcinoma epitopes (EPs) which can be immunodetected in about 90% of adenocarcinomas (CAs). To study the location of T and Tn EPs and their relations to adhesion plaques on CA cells, immunogold-silver staining method was employed at scanning electron microscope (SEM) level. Human breast CA cells grown on coverslips were fixed in paraformaldehyde and glutaraldehyde, reacted with cocktails of monoclonal antibodies against T or Tn EPs, followed by incubation with 10 nm gold conjugated goat anti-mouse immuno-globulins. The positive gold particle labelling was amplified with silver enhancement solution, and the specimens were then routinely critical point dried, sputter-coated with palladium and observed under SEM. The studies show that T and Tn EPs are not randomly distributed on CA cell surface; they are aggregated at the adhesion plaque area. These results confirm that T and Tn EPs play roles in CA cell adhesion, and suggest that they may represent the initial points of contact by immuno-effectors and therefore can be utilized in immunointervention and anti-adhesion therapy against CA.


Profiles of ARGs and their relationships with antibiotics, metals and environmental parameters in vertical sediment layers of three lakes in China.
Antibiotic resistance is a global health problem, and the role of antibiotics and metal pollution in antibiotic resistance in sediment biocenosis is limited. The occurrence and relationship between antibiotic resistance genes (ARGs), antibiotics, metals and environmental parameters were investigated in vertical layers of sediments in rural and urban lakes. Generally, the total concentrations of seven antibiotics were significantly higher in the rural lake (Lake Taihu = 96%) than in the urban lakes (Xuanwu = 0.3%, Wulongtan = 3%), while similar concentrations were observed for metals (Taihu (34%), Xuanwu (33%) and Wulongtan (33%)). The concentration of metals and antibiotics were mostly higher in the surface sediment layers than the deeper ones (for antibiotics; surface layers = 89%, deeper layer = 11%, for metals; surface = 65%, deep = 35%). The ARGs showed no significant difference between surface and deeper sediments (surface = 48%, deep = 52%, p < 0.05). The potential ecological risk index of Ni, Cu, Zn, Cr, Mn, As, Cd, and Pb contamination showed that Lake Taihu and Wulongtan had moderate ecological risks while Lake Xuanwu had a low ecological risk. Pearson coefficient and network analysis showed that direct and indirect relationship existed among antibiotics, metals, environmental parameters, and ARGs, and the relationship was linked by key environmental components. tetA, blaTEM, SDZ, TOC, OFL, Cd, OTC, NOR, Ni, sulA, AUR, TC, DOX and TN were the major factors that influence the distribution of resistance genes, forming a complex network mechanism of antibiotic resistance. Our study revealed that antibiotics and heavy metals are widely distributed in the surficial sediments and the proliferation of ARGs are influenced by some key environmental components.


Acromegaloidism with normal growth hormone secretion associated with X-tetrasomy.
We reported a case of a 26-year-old female who was referred to our clinic with the diagnosis of possible acromegaly. She was born from a term pregnancy by forceps delivery. The patient was diagnosed as having hip luxation at one month and spoke her first word at 15 months. She had been diagnosed at the age of 9 years old as having perinatal encephalopathy with intellectual and motor affectation. Since this period of time she has undergone an insidious change in her appearance, mainly comprising progressive coarsening of the face. For this reason she was submitted to our clinic with presumed acromegaly. Dynamic tests of growth hormone secretion ruled out such a diagnosis. The Patient was considered as having "acromegaloidism", a term used for patients whom manifest clinical features of acromegaly but do not present a demonstrable growth hormone hypersecretion. Subsequently cytogenetic evaluation revealed an infrequent chromosome pattern: X-Tetrasomy. In the present article a differential diagnosis of acromegaloidism and the potential role of genes present on X-chromosome involved in human growth such as SHOX gene are discussed. Overdosification of SHOX gene might explain tall stature of girls with X-tetrasomy. Our observation suggested that X-tetrasomy should be considered in the differential diagnosis of acromegaloidism. Furthermore, this may lead to the identification of new genes in the X-chromosome that are important for growth of facial structures.


T1R2 receptor-mediated glucose sensing in the upper intestine potentiates glucose absorption through activation of local regulatory pathways.
Beyond the taste buds, sweet taste receptors (STRs; T1R2/T1R3) are also expressed on enteroendocrine cells, where they regulate gut peptide secretion but their regulatory function within the intestine is largely unknown. Using T1R2-knock out (KO) mice we evaluated the role of STRs in the regulation of glucose absorption in vivo and in intact intestinal preparations ex vivo. STR signaling enhances the rate of intestinal glucose absorption specifically in response to the ingestion of a glucose-rich meal. These effects were mediated specifically by the regulation of GLUT2 transporter trafficking to the apical membrane of enterocytes. GLUT2 translocation and glucose transport was dependent and specific to glucagon-like peptide 2 (GLP-2) secretion and subsequent intestinal neuronal activation. Finally, high-sucrose feeding in wild-type mice induced rapid downregulation of STRs in the gut, leading to reduced glucose absorption. Our studies demonstrate that STRs have evolved to modulate glucose absorption via the regulation of its transport and to prevent the development of exacerbated hyperglycemia due to the ingestion of high levels of sugars.


The fibrosing process in so-called organized diffuse alveolar damage. An immunohistochemical study of the change from hyaline membrane to membranous fibrosis.
On the assumption that some cases of organized diffuse alveolar damage (DAD) result from organization of hyaline membrane, we collected nine autopsy cases of DAD in various stages of the fibrosing process from hyaline membrane to membranous fibrosis and studied changes in the basement membrane and epithelial cells immunohistochemically. In the majority of cases, the following sequence of events was assumed: the hyaline membrane is first formed at the tip of the alveolar septum, a part of the alveolar duct wall where epithelial cells have disappeared. With time it elongates and completely covers alveolar mouths. In the organizing stage, fibroblasts start to permeate through the alveolar duct walls to replace the hyaline membrane completely and to form membranous fibrous tissue. In a few cases, however, fibrous tissue will fill alveolar spaces to form intraluminal diffuse fibrosis. Alveolar epithelial cells and the basement membrane of the alveolar walls are well preserved until the end of the organizing stage when the basement membrane becomes distorted. We believe that membranous fibrosis represents a form of "alveolar duct damage" and that it differs from diffuse fibrosis, which is indicative of diffuse alveolar damage in the true sense.


Asthma and Attendance in Urban Schools.
Asthma is linked to student absenteeism, a risk factor for poor achievement and school dropout. Studies of asthma and absenteeism have common limitations, including relying on parent-reported asthma, which may be unreliable and prone to selection, and inadequately accounting for confounding health and social risks. Therefore, the rate of absenteeism attributable to asthma and the extent to which better asthma control would translate into better attendance remain unclear. Participants were 1,194 students in 2 large urban US schools (1 elementary, 1 middle) in 2016-2018. Student asthma was assessed based on parent report on health forms, student-reported asthma-related emergency department/hospitalization or medication use, and school health center record of asthma. Multiple imputation was used to reduce selection from missing asthma reports. The relationship between asthma and school district-reported days absent was estimated using Poisson random intercept regression, accounting for health and demographic covariates. Parent-reported ever asthma (27%) was not associated with absenteeism in adjusted models. Student-reported asthma health care or medication use (16%) and school health center record of asthma (17%) were associated with higher absenteeism (incidence rate ratio [IRR], 1.16; 95% confidence interval [CI], 1.01-1.35 and IRR, 1.21; 95% CI, 1.09-1.34, respectively). Student-reported asthma and school health center record of asthma were associated with 1.9 and 1.5 absences per year, respectively. Student-reported and school health center record of asthma explained 14% to 18% of student absenteeism, even after accounting for other health and social risks. When possible, student reports should supplement parent reports to ensure that students with asthma are identified and obtain access to care.


Lethal consequences of simulated solar radiation on the nematode Caenorhabditis elegans in the presence and absence of photosensitizers.
The partial destruction of the earth's protective ozone layer has raised concerns about the impact of increased UV radiation on the earth's biological systems. In this study, polychromatic light sources were employed to observe the biological responses of the soil nematode Caenorhabditis elegans to simulated solar UV. Using various filter combinations, action spectra were constructed that approximated those generated previously with mono-chromatic radiation. In both cases, a mutant strain (rad-3) progressively lost its hypersensitivity as shorter wave-lengths were filtered out. In addition, both wild type and radiation-sensitive (rad) mutants were irradiated with several combinations of filtered light sources in the presence and absence of two exogenous photosensitizers (ethidium bromide and bromodeoxyuridine). Treatment with either of the introduced photosensitizers increased photosensitivity to solar UV. Solar UV also induced a fluence-dependent reduction in fertility in wild-type animals. These experiments extend previous data and substantially expand our understanding of the biological responses of C. elegans to solar radiation.


Nematode larvae infecting Priacanthus arenatus Cuvier, 1829 (Pisces: Teleostei) in Brazil.
From July to December, 2013, thirty Priacanthus arenatus specimens commercialized in the cities of Niterói and Rio de Janeiro, State of Rio de Janeiro, were acquired. The fish were necropsied and filleted to investigate the presence of nematode larvae. Twenty fish (66.7%) out of the total were parasitized by nematode larvae. A total of 2024 larvae were collected; among them, 30 third-instar larvae of Anisakis sp. showed prevalence (P) = 20%, mean abundance (MA) = 1, and the mean intensity (MI) = 5, and infection sites (IS) = caecum, stomach, liver, and mesentery; and 1,994 third-instar larvae (1,757 encysted and 237 free) of Hysterothylacium deardorffoverstreetorum with P = 66.7%, MA = 66.5, and MI = 99.7, and IS = spleen, caecum, stomach, liver, mesentery, and abdominal muscle. This is the first study to report H. deardorffoverstreetorum and Anisakis sp. larvae parasitizing P. arenatus.


Improved lipid production in oleaginous brackish diatom Navicula phyllepta MACC8 using two-stage cultivation approach.
A two-stage cultivation method involving the initial growth in optimized conditions for biomass production followed by those for lipid production in oleaginous brackish diatom Navicula phyllepta MACC8 resulted in a proportional increase of lipid concentration along with biomass production. The diatom was further subjected to stress conditions by altering the nutrient components such as nitrate, phosphate, silicate, and temperature. Silicon deprivation resulted in the highest lipid percentage of 28.78% of weight at the end of the 18th day of the second stage. A significant increase in lipid content was observed on the complete removal of the nutrients silicon and urea one at a time, while the biomass showed a considerable reduction. The application of multiple nutrient stress conditions had a profound influence on the increased rate of lipid production. A combination of phosphate deprivation, silicate limitation and temperature reduction resulted in a significant increase in lipid percentage of 32.13% at the cost of reduced biomass (1.1 g L-1), whereas phosphate deprivation, urea limitation, and temperature reduction resulted in lipid percentage of 27.58% with a biomass of 1.44 g L-1 at the end of the second stage. Further, the results were supported by Nile red staining, FTIR, fatty acid profile and oxidative stress marker analyses. The changes in biochemical composition and oxidative stress parameters within the various stress conditions demonstrated the profound influence of the selected stress factors on the biodiesel productivity of the diatom, besides its stress tolerance. A two-phase culturing system, with multifactor stress application, especially nitrogen limitation along with phosphate starvation and temperature stress, would be the suitable method for gaining maximum biomass productivity and lipid content in diatom Navicula phyllepta MACC8 towards biofuel production.


Clinical and microbiological evaluation of piperacillin in elective biliary surgery.
Fifty patients undergoing electric biliary surgery were given piperacillin 2 g i.m. 2 h preoperatively followed by 2 g i.v. at the beginning of the operation. Venous blood and bile from the gall bladder and common bile duct were assayed for piperacillin. Blood levels exceeded 100 mg 1(-1) in all instances unless the protocol was not followed. Both gallbladder and common bile duct bile levels exceeded 50 mg 1(-1), and the only exceptions were due to poor penetration into three obstructed gallbladders. Common bile duct levels exceeded 50 mg 1(-1) even in the presence of obstructive jaundice. Only one patient developed a minor postoperative wound infection.


Enhanced handling and positioning in early infancy advances development throughout the first year.
Behaviors emerge, in part, from the interplay of infant abilities and caregiver-infant interactions. Cross-cultural and developmental studies suggest caregiver handling and positioning influence infant development. In this prospective, longitudinal study, the effects of 3 weeks of enhanced handling and positioning experiences provided to 14 infants versus control experiences provided to 14 infants at 2 months of age were assessed with follow-up through 15 months of age. Behaviors in prone were immediately advanced. Short-term advancements occurred in multiple behaviors, including prone, head control, reaching, and sitting behaviors. Longer term advancements, up to 12 months after the experience period, occurred in object transfer, crawling and walking behaviors. This suggests broad and long-lasting changes can arise via brief periods of change in caregiver-infant interactions.


HIV Testing Uptake Among Ethiopian Rural Men: Evidence from 2016 Ethiopian Demography and Health Survey Data.
Human immunodeficiency virus (HIV) testing coverage among men remains low in Ethiopia; the problem of limited HIV testing coverage is worst in rural areas. Therefore, this study aims to identify factors associated with HIV testing uptake among rural men in Ethiopia. Data from 10,187 rural men was extracted from the 2016 Ethiopian Demography and Health Survey. All analyses were performed using the complex sample analysis procedure to account for the multistage sampling. Bivariable and multivariable regression analyses were performed to identify factors associated with HIV testing uptake. Statistical significance was defined as a 95% Confidence Interval (CI) with a p-value of less than 0.05. Overall, only 40.3% of rural men have ever been tested for HIV. Being aged 31-44 years (Adjusted Odds Ratio (AOR) =1.12, 95% CI [1.01-1.42]), living in developed regions (AOR=1.43, 95% CI [1.09-1.88]), engaging in non-agricultural activities (AOR = 1.27, 95% CI [1.05-1.52]), being Muslim (AOR = 2.07; 95% CI [1.67-2.67]), having comprehensive knowledge about HIV (AOR =1.31, 95% CI [1.12-1.54]), being from a medium (AOR = 0.56, 95% CI [0.47-0.93]) and rich (AOR = 0.80, 95% CI [0.56-0.80]) households, attending primary (AOR = 0.21, 95% CI [0.16-0.28]) and secondary (AOR = 0.35, 95% CI [0.25-0.35]) school, having their first sexual experience at the age of 17 or younger (AOR = 0.26, 95% CI [0.19-0.93]), having discriminatory attitudes towards HIV patients (AOR = 0.67, 95% CI: 0.47-0.93) and having no health insurance coverage (AOR = 0.54, 95% CI [0.42-0.69]) were significantly associated with HIV testing uptake. HIV testing uptake among rural men was low. Strengthening awareness programmes on HIV and HIV testing, integrating HIV testing with all other healthcare, strengthening partner accompany and HIV testing during pregnancy and delivery, and providing home-based HIV testing may increase HIV testing uptake.


Fabricating a crown under an existing removable partial denture with impression scanning and CAD-CAM technology.
Retrofitting a new crown to an existing removable partial denture (RPD) is a challenging procedure. Recently, intraoral scanners (IOSs) have been successfully used to solve this issue. However, purchase of IOSs is necessary, and most clinicians still use the conventional impression technique. This article describes a combined conventional and digital approach to fabricating a new crown under an RPD without an IOS.


Low dielectric permittivity of water at the membrane interface: effect on the energy coupling mechanism in biological membranes.
Protonmotive force (the transmembrane difference in electrochemical potential of protons, ) drives ATP synthesis in bacteria, mitochondria, and chloroplasts. It has remained unsettled whether the entropic (chemical) component of relates to the difference in the proton activity between two bulk water phases (deltapH(B)) or between two membrane surfaces (deltapH(S)). To scrutinize whether deltapH(S) can deviate from deltapH(B), we modeled the behavior of protons at the membrane/water interface. We made use of the surprisingly low dielectric permittivity of interfacial water as determined by O. Teschke, G. Ceotto, and E. F. de Souza (O. Teschke, G. Ceotto, and E. F. de Sousa, 2001, PHYS: Rev. E. 64:011605). Electrostatic calculations revealed a potential barrier in the water phase some 0.5-1 nm away from the membrane surface. The barrier was higher for monovalent anions moving toward the surface (0.2-0.3 eV) than for monovalent cations (0.1-0.15 eV). By solving the Smoluchowski equation for protons spreading away from proton "pumps" at the surface, we found that the barrier could cause an elevation of the proton concentration at the interface. Taking typical values for the density of proton pumps and for their turnover rate, we calculated that a potential barrier of 0.12 eV yielded a steady-state pH(S) of approximately 6.0; the value of pH(S) was independent of pH in the bulk water phase under neutral and alkaline conditions. These results provide a rationale to solve the long-lasting problem of the seemingly insufficient protonmotive force in mesophilic and alkaliphilic bacteria.


SNP set analysis for detecting disease association using exon sequence data.
Rare variants are believed to play an important role in disease etiology. Recent advances in high-throughput sequencing technology enable investigators to systematically characterize the genetic effects of both common and rare variants. We introduce several approaches that simultaneously test the effects of common and rare variants within a single-nucleotide polymorphism (SNP) set based on logistic regression models and logistic kernel machine models. Gene-environment interactions and SNP-SNP interactions are also considered in some of these models. We illustrate the performance of these methods using the unrelated individuals data from Genetic Analysis Workshop 17. Three true disease genes (FLT1, PIK3C3, and KDR) were consistently selected using the proposed methods. In addition, compared to logistic regression models, the logistic kernel machine models were more powerful, presumably because they reduced the effective number of parameters through regularization. Our results also suggest that a screening step is effective in decreasing the number of false-positive findings, which is often a big concern for association studies.


Mitral valve repair for functional mitral regurgitation in end-stage dilated cardiomyopathy: role of the "edge-to-edge" technique.
The aim of this study was to assess the results of mitral valve (MV) repair in functional mitral regurgitation because of end-stage dilated cardiomyopathy (DCM). Seventy-seven patients with end-stage idiopathic (26 patients) or ischemic (51 patients) DCM underwent MV repair for functional mitral regurgitation (3 to 4+/4+). Fifty-eight patients (75.3%) were in New York Heart Association class III, and 19 (24.6%) were in IV. In 23 patients (29.8%) with a coaptation depth <1 cm, an isolated undersized annuloplasty was used. In the remaining 54 (70.1%), with a coaptation depth > or =1 cm, the "edge-to-edge" technique was associated with the annuloplasty. In most of the cases (88.3%), a complete rigid/semirigid ring was used. Concomitant coronary artery bypass graft was performed in 39 patients (50.6%). Hospital mortality was 3.8% (3 of 77). Actuarial survival was 90.7+/-3.64%, and freedom from cardiac events was 81.8+/-7.96% at 2.7 years. At a mean follow-up of 18.4+/-9.8 months (range, 1 month to 5 years) New York Heart Association class improved from 3.4+/-0.4 to 1.4+/-0.6 (P<0.0001). Mitral repair failure (recurrence of MR > or =3+/4+) was documented in 7 patients (9%): 2 in the edge-to-edge (2 of 54, 3.7%) and 5 in the isolated annuloplasty group (5 of 23, 21.7%) (P=0.03). Freedom from repair failure at 1.5 years was 95.0+/-3.4% and 77+/-12.1%, respectively (P=0.04). The absence of the edge-to-edge was the only predictor of repair failure (P=0.03). When residual MR was absent or mild, a reverse left ventricular remodeling was clearly documented. In patients with end-stage DCM, MV repair is feasible with low hospital mortality and important symptomatic improvement. The association of the edge-to-edge technique to the undersized annuloplasty can significantly improve the durability of the repair.


Enhanced podophyllotoxin production from Agrobacterium rhizogenes transformed cultures of Podophyllum hexandrum.
Podophyllotoxin, a potent chemotherapeutic agent is obtained from Podophyllum hexandrum Royle. Embryos of P. hexandrum were transformed using different strains of Agrobacterium rhizogenes viz. A4, 15834, K599. Transformed nature of the calli was ascertained and the cultures were further maintained as individual clones. HPLG analysis of transformed cultures depicted a three-fold increase in podophyllotoxin content in comparison to controls.


A cytogenetic study of hospital workers occupationally exposed to radionuclides in Serbia: premature centromere division as novel biomarker of exposure?
The health risk of chronic exposure to radionuclides includes changes in the genome (e.g., chromosomal aberrations and micronuclei) that increase chromosomal instability. There are also other phenomena, which seem to appear more frequently in metaphases of exposed persons (such as premature centromere division). The aim of this study was to discover whether or not there is correlation between incidence of named cytogenetic changes in persons occupationally exposed to radionuclides in comparison with unexposed control group, and if significant correlation is determined, can premature centromere division be consider as a biomarker of radiation exposure? The exposed group comprised 50 individuals occupationally exposed to radionuclides. The reference control group consisted of 40 unexposed individuals. Chromosomal aberrations, micronuclei and premature centromere division were analyzed according to a standard International Atomic Energy Agency protocol. Statistical analyses were performed using SPSS 17.0 statistics. The means for analyzed cytogenetic changes were significantly higher in the exposed group. Positive correlation between them was found in exposed group. Premature centromere division parameter PCD5-10 was selected as particularly suitable for separating groups (exposed/unexposed). Identification of other phenomena related to radionuclide exposure, beside well known, may clarify recent problems in radiobiology concerning the biological response to low doses of ionizing radiation and its consequences.


Combinatorial targeting of menin and the histone methyltransferase DOT1L as a novel therapeutic strategy for treatment of chemotherapy-resistant ovarian cancer.
Ovarian cancer (OC) is characterized by a low response rate and high frequency of resistance development to currently available treatments. The therapeutic potential of histone methyltransferase DOT1L inhibitor in OC cells has been demonstrated, but optimal efficacy and safety of this targeted therapy approach still require improvement. We set forth to evaluate if this problem can be overcome by combinatorial targeting of this epigenetic modifier and menin, one of its functional partners in chromatin. siRNA-mediated gene knock-down and pharmacological inhibition of menin, a key component of the MLL/SET1 complex and a fitness gene in OC cells, coupled to cell proliferation assays on a panel of high grade serous OC cell lines, including chemotherapy-sensitive and -resistant clones, were applied in order to evaluate how depletion or blockade of this enzyme influences growth and viability of OC cells. RNA sequencing was applied to identify menin target genes and pathways, and the effects of combined inhibition of menin and DOT1L on growth and transcriptome of these OC models were evaluated. Silencing and pharmacological inhibition of menin exert antiproliferative effects in all OC cells tested and, in PEO1 and PEO4 cells, a profound impact on transcriptome via down-regulation of cell cycle regulatory pathways, aryl hydrocarbon receptor, MYC and KRAS signalling. We demonstrated association of menin and DOT1L in OC cells and identified a subset of genes co-regulated by the two factors. Interestingly, co-treatment with DOT1L and menin pharmacological inhibitors exerts an additive effect on growth inhibition on chemotherapy-sensitive and -refractory OC cells mediated by transcriptome changes controlled by menin and DOT1L activities. These results indicate that menin functionally cooperates with DOT1L in OC cells modulating transcription of genes involved in key cellular functions including, among others, cell proliferation and survival, that are strongly affected by combined inhibition of these two epigenetic regulators, suggesting that this may represent a novel therapeutic strategy for chemotherapy-resistant OCs. NA; The manuscript does not contain clinical trials.


The time course of short-term hypertrophy in the absence of eccentric muscle damage.
It has been proposed that the increase in skeletal muscle mass observed during the initial weeks of initiating a resistance training program is concomitant with eccentric muscle damage and edema. We examined the time course of muscle hypertrophy during 4 weeks of concentric-only resistance training. Thirteen untrained men performed unilateral concentric-only dumbbell curls and shoulder presses twice per week for 4 weeks. Sets of 8-12 repetitions were performed to failure, and training loads were increased during each session. Subjects consumed 500 ml of whole milk during training. Assessments of soreness, lean mass, echo intensity, muscle thickness, relaxed and flexed arm circumference, and isokinetic strength were performed every 72 or 96 h. Soreness, echo intensity, relaxed circumference, and peak torque data did not significantly change. Significant increases in lean mass, muscle thickness, and flexed circumference were observed within seven training sessions. Lean mass was elevated at tests #7 (+109.3 g, p = .002) and #8 (+116.1 g, p = .035), with eight different subjects showing changes above the minimal difference of 139.1 g. Muscle thickness was elevated at tests #6 (+0.23 cm, p = .004), #7 (+0.31 cm, p < .001), and #8 (+0.27 cm, p < .001), with ten subjects exceeding the minimal difference of 0.24 cm. There were no changes for the control arm. In individuals beginning a resistance training program, small but detectable increases in hypertrophy may occur in the absence of eccentric muscle damage within seven training sessions.


Levels of paraoxonase, an index of antioxidant defense, in patients with active sarcoidosis.
Oxidative mechanisms are currently discussed as playing a crucial role in the genesis of inflammatory lung diseases. We aimed to evaluate the oxidant-antioxidant balance in the pathogenesis and activity of sarcoidosis and to search if the change in the level of PON can be taken as an activity marker. 26 active sarcoidosis subjects aged 41.3+/-12.9 years, 37 inactive subjects aged 39.6+/-11.7 years and 48 control subjects aged 48.9+/-2.5 years were recruited in our study. Malondialdehyde (MDA), paraoxonase1 (PON1) and oxidized low density lipoprotein (oxLDL) levels in serum were analyzed by spectrophotometric, kinetic, and ELISA methods, respectively. PON1 levels were significantly lower in the active disease state than both the inactive form and control groups. MDA levels were significantly higher in active sarcoidosis than both the inactive disease and control groups, and oxLDL levels were significantly higher in the active disease group than the inactive group and control group. The level of PON1 in the inactive disease group is not significantly different from the control group while the oxLDL and MDA levels of inactive group is significantly higher than the control group (p<0.001). There was a negative correlation between the PON1 activities and MDA values in both active and inactive groups (p=0.008). Oxidative stress increases in sarcoidosis might be due to both increase in lipid peroxidation and decrease in antioxidant status (PON1) and the relationship between oxidative status and the activation of the disease should be discussed by comparing the previously known activation criteria.


Landmark methods for forms without landmarks: morphometrics of group differences in outline shape.
Morphometrics, a new branch of statistics, combines tools from geometry, computer graphics and biometrics in techniques for the multivariate analysis of biological shape variation. Although medical image analysts typically prefer to represent scenes by way of curving outlines or surfaces, the most recent developments in this associated statistical methodology have emphasized the domain of landmark data: size and shape of configurations of discrete, named points in two or three dimensions. This paper introduces a combination of Procrustes analysis and thin-plate splines, the two most powerful tools of landmark-based morphometrics, for multivariate analysis of curving outlines in samples of biomedical images. The thin-plate spline is used to assign point-to-point correspondences, called semi-landmarks, between curves of similar but variable shape, while the standard algorithm for Procrustes shape averages and shape coordinates is altered to accord with the ways in which semi-landmarks formally differ from more traditional landmark loci. Subsequent multivariate statistics and visualization proceed mainly as in the landmark-based methods. The combination provides a range of complementary filters, from high pass to low pass, for effects on outline shape in grouped studies. The low-pass version is based on the spectrum of the spline, the high pass, on a familiar special case of Procrustes analysis. This hybrid method is demonstrated in a comparison of the shape of the corpus callosum from mid-sagittal sections of MRI of 25 human brains, 12 normal and 13 with schizophrenia.


[Evaluation of serum cytokines in small cell lung cancer and its clinical significance].
It has been proven that serum cytokines could be changed in the early stage of patients with small cell lung cancer (SCLC). The current research investigates the different changes of cytockines and searches for potential biomarkers to improve the situation of the early diagnosis of SCLC. The differential expression cytokines were detected using Reybiotech G6/G7 analysis of microarrays in the serum of 4 SCLC patients, 4 normal controls, and 4 phlegmonosis controls. The differential cytokines were confirmed by enzyme-linked immunosorbentassay (ELISA) in 197 SCLC patients, 180 normal controls, and 97 phlegmonosis controls. The levels of the 4 most valuable biomarkers in SCLC, including Leptin, MSP-α, uPAR, and MIP-1β, were significantly higher than that in the other groups with microaaray screening (P<0.05). The ELISA results showed that the uPAR are much higher in SCLC patients than that in the controls, in which the diagnostic sensitivity and specificity were 52.93% and 83.36%, respectively. The Leptin level was significantly higher in SCLC patients who do not have obvious body weight lost, whereas no difference were found in the SCLC who have obvious body weight lost compared with control groups. The diagnostic sensitivity and specificity of Leptin are 50.11% and 86.77%. The MSP-α and MIP-1β level have no significant difference among the three groups. The uPAR elevated level is significant in indicating SCLC diagnoses. The Leptin may be associated with SCLC in patients who do not have a change in weight.


[Connection of immune status, nutritional status and postoperative complications in patients after surgery for organic esophageal stricture].
The postoperative complications were analysed in 64 patients after operation for stricture of the esophagus. The underfeeding in consequence of the esophagus stricture reduced the cellular immune functions and increased the operative risk. The comparison of the feeding and immune parameters of patients with benign and malign strictures of the esophagus showed that the poor immune reactivity is caused by the underfeeding first of all and not by the immune depression due the tumor.


Ovarian plasminogen activator: relationship to ovulation and hormonal regulation.
A technique is described for detecting fibrinolytic activity of single cells in culture. This method was applied to the analysis of rat ovarian granulosa cells. Cells obtained from follicules shortly before ovulation show high levels of fibrinolytic activity. This activity is plasminogen-dependent, indicating that it is due to plasminogen activator. The appearance of this activity is correlated with ovulation by temporal and functional criteria, and can be demonstrated both in immature animals primed with hormones and in mature cycling animals. Granulosa cell cultures can be stimulated to release plasminogen activator by exposure in vitro either to luteinizing hormone or to dibutyryl cyclic AMP.


Enhanced mixing state of black carbon with nitrate in single particles during haze periods in Zhengzhou, China.
Black carbon (BC) plays an important role in air quality and climate change, which is closely associated with its mixing state and chemical compositions. In this work the mixing state of BC-containing single particles was investigated to explore the evolution process of ambient BC particles using a single particle aerosol mass spectrometer (SPAMS) in March 2018 in Zhengzhou, China. The BC-containing particles accounted for 61.4% of total detected ambient single particles and were classified into five types including BC-nitrate (BC-N, 52.3%) as the most abundant species, followed by BC-nitrate-sulfate (BC-NS, 22.4%), BCOC (16.8%), BC-fresh (BC-F, 4.5%) and BC-sulfate particles (BC-S, 4.0%). With enhancement of the ambient nitrate concentration, the relative peak area (RPA) of nitrate in BC-N and BCNS particles both increased, yet only the number fraction (Nf) of BCN particles increased while the Nf of BC-NS particles decreased, suggesting that the enhanced mixing state of BC with nitrate was mainly due to the increase in the ambient nitrate mass concentration. In addition, the Nf of BC-N decreased from 65.3% to 28.4% as the absorbing Ångström exponents (AAE) of eBC increased from 0.75 to 1.45, which indicated the reduction of light absorption ability of aged BC particles with the enhanced formation of BC-N particles. The results of this work indicated a change in the mixing state of BC particles due to the dominance of nitrate in PM2.5, which also influenced the optical properties of aged BC particles.


Pancreatic Cancer Organoids in the Field of Precision Medicine: A Review of Literature and Experience on Drug Sensitivity Testing with Multiple Readouts and Synergy Scoring.
Pancreatic ductal adenocarcinoma (PDAC) is a silent killer, often diagnosed late. However, it is also dishearteningly resistant to nearly all forms of treatment. New therapies are urgently needed, and with the advent of organoid culture for pancreatic cancer, an increasing number of innovative approaches are being tested. Organoids can be derived within a short enough time window to allow testing of several anticancer agents, which opens up the possibility for functional precision medicine for pancreatic cancer. At the same time, organoid model systems are being refined to better mimic the cancer, for example, by incorporation of components of the tumor microenvironment. We review some of the latest developments in pancreatic cancer organoid research and in novel treatment design. We also summarize our own current experiences with pancreatic cancer organoid drug sensitivity and resistance testing (DSRT) in 14 organoids from 11 PDAC patients. Our data show that it may be necessary to include a cell death read-out in ex vivo DSRT assays, as metabolic viability quantitation does not capture actual organoid killing. We also successfully adapted the organoid platform for drug combination synergy discovery. Lastly, live organoid culture 3D confocal microscopy can help identify individual surviving tumor cells escaping cell death even during harsh combination treatments. Taken together, the organoid technology allows the development of novel precision medicine approaches for PDAC, which paves the way for clinical trials and much needed new treatment options for pancreatic cancer patients.


Tele-yoga in the management of ankylosing spondylitis amidst COVID pandemic: A prospective randomized controlled trial.
Ankylosing spondylitis (AS) signficantly affect day to day activities contributing to signficant disability. Patients with AS often report to have psychological problems and poor quality of life (QoL). This study investigates the effect of a three-month tele-yogic intervention on disease activity, functional index, inflammatory markers, quality of life and mental health measures in patients with AS. One hundred and twenty AS patients were assigned to either the yoga intervention group (YG) or the control group (CG). The YG (n = 57) received a 60-min structured yoga module online for 3 months in addition to standard medical care. The CG participants (n = 52) received only standard care during the same period. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis-Quality of Life (ASQOL) and psychological and inflammatory biomarkers were assessed at baseline and after three months. YG showed significant improvement in BASDAI (p = 0.001), anxiety (p = 0.0004), and depression (p = 0.001) at three months compared to baseline. The CG showed no significant change in similar outcome measures. At three months, the intervention resulted in a significant improvement in BASDI (-0.79; 95% CI (-1.3, to -0.29); p = 0.0021), BASFI (-0.86, 95% CI (-1.59, to -0.14); p = 0.0193), anxiety (-0.42, 95% CI (-0.84 to -0.01), p = 0.0468), and AS-QoL (-3.37; 95% CI (-5.21 to 1.53); p = 0.0004) compared to the CG. The present study suggests that yoga helps improve pain, functional index, and mental health in patients with AS. Tele-yoga intervention is feasible and effective in treating AS.


Rapid increase in the prevalence of obesity in elementary school children.
Three critical periods have been suggested for the development of obesity during childhood: fetal, ages 4-6 y, and adolescence. The prevalence of obesity in elementary school children is increasing in Japan, and the present study examines whether this rising prevalence occurs during the elementary school period (age 6-11 y) or is occurring prior to entry into elementary school. Repeated cross-sectional sampling of cohorts of children for the prevalence of obesity. The data from 81 264 first grade and 87 849 seventh grade children (94 and 87% of the total populations, respectively) between 1989 and 2002 in Kagoshima City were analyzed. Data were also obtained from nationwide surveys published by the Ministry of Japan between 1989 and 2001. Obesity was defined by the body mass index for an age- and sex-specific 95th percentile cutoff point in Japanese children. Trends in obesity and odds ratios of the prevalence of obesity were also determined. The period 1989-2001/2 showed significant increases in the prevalence of obesity for both genders, in both first and seventh grades, and in both Kagoshima City and nationwide. The odds ratios for the prevalence of obesity of 12-y-old children calculated against the prevalence of obesity within the same cohort at 6 y old revealed that a significant risk for development of obesity during the elementary school years applied only to boys from around 1993 onward in Kagoshima City and applied throughout the study period in nationwide Japan. Obesity prevalence increases for boys during elementary school years but does not significantly increase for girls. A rising trend for becoming obese before starting elementary school was present for both boys and girls over the period 1989-2001. Educational programs to improve nutrition and physical activity, especially for boys, are becoming increasingly necessary.


Did biogeographical processes shape the monogenean community of butterflyfishes in the tropical Indo-west Pacific region?
Geographical distribution of parasite species can provide insights into the evolution and diversity of parasitic communities. Biogeography of marine parasites is poorly known, especially because it requires an understanding of host-parasite interactions, information that is rare, especially over large spatial scales. Here, we have studied the biogeographical patterns of dactylogyrid parasites of chaetodontids, one of the most well-studied fish families, in the tropical Indo-west Pacific region. Dactylogyrid parasites were collected from gills of 34 butterflyfish species (n=560) at nine localities within an approximate area of 62millionkm2. Thirteen dactylogyrid species were identified, with richness ranging from 6 to 12 species at individual localities. Most dactylogyrid communities were dominated by Haliotrema angelopterum or Haliotrema aurigae, for which relative abundance was negatively correlated (ρ=-0.59). Parasite richness and diversity were highest in French Polynesia and the Great Barrier Reef (Australia) and lowest in Palau. Three biogeographic regions were identified based on dactylogyrid dissimilarities: French Polynesia, characterised by the dominance of H. angelopterum, the western Pacific region dominated by H. aurigae, and Ningaloo Reef (Australia), dominated by Euryhaliotrema berenguelae. Structure of host assemblages was the main factor explaining the dissimilarity (turnover and nestedness components of the Bray-Curtis dissimilarity and overall Bray-Curtis dissimilarity) of parasite communities between localities, while environment was only significant in the turnover of parasite communities and overall dissimilarity. Spatial structure of localities explained only 10% of the turnover of parasite communities. The interaction of the three factors (host assemblages, environment and spatial structure), however, explained the highest amounts of variance of the dactylogyrid communities, indicating a strong colinearity between the factors. Our findings show that spatial arrangement of chaetodontid dactylogyrids in the tropical Indo-west Pacific is primarily characterised by the turnover of the main Haliotrema spp., which is mainly explained by the structure of host assemblages.


Designer skin: lineage commitment in postnatal epidermis.
The epidermis is populated by stem cells that produce daughters that differentiate to form the interfollicular epidermis, hair follicles and sebaceous glands. Diffusible factors, cell-cell contact and extracellular matrix proteins are all important components of the microenvironment of individual stem cells and profoundly affect the differentiation pathways selected by their progeny. Here, we summarize what is known about stem-cell populations and lineage relationships within the epidermis. We also present evidence that postnatal epidermis can be reprogrammed, altering the number and location of cells that differentiate along specific epidermal lineages.


Prediction of dissolution time and coating thickness of sustained release formulations using Raman spectroscopy and terahertz pulsed imaging.
Raman spectroscopy was implemented successfully as a non-invasive and rapid process analytical technology (PAT) tool for in-line quantitative monitoring of functional coating. Coating experiments were performed at which diprophylline tablets were coated with a sustained release formulation based on Kollicoat SR 30 D. Using PLS a multivariate model was constructed by correlating Raman spectral data with the mean dissolution time as determined by dissolution testing and the coating thickness as measured by terahertz pulsed imaging. By performing in-line measurements it was possible to monitor the progress of the coating process and to detect the end point of the process, where the acquired coating amount was achieved for the desired MDT or coating thickness.


Investigation of the origins of human autosomal inversions.
A significant proportion of both pericentric and paracentric inversions have recurrent breakpoints and so could either have arisen through multiple independent events or be identical by descent (IBD) with a single common ancestor. Of two common variant inversions previously studied, the inv(2)(p11q13) was genuinely recurrent while the inv(10)(p11.2q21.2) was IBD in all cases tested. Excluding these two variants we have ascertained 257 autosomal inversion probands at the Wessex Regional Genetics Laboratory. There were 104 apparently recurrent inversions, representing 35 different breakpoint combinations and we speculated that at least some of these had arisen on more than one occasion. However, haplotype analysis identified no recurrent cases among eight inversions tested, including the variant inv(5)(p13q13). The cases not IBD were shown to have different breakpoints at the molecular cytogenetic level. No crossing over was detected within any of the inversions and the founder haplotypes extended for variable distances beyond the inversion breakpoints. Defining breakpoint intervals by FISH mapping identified no obvious predisposing elements in the DNA sequence. In summary the vast majority of human inversions arise as unique events. Even apparently recurrent inversions, with the exception of the inv(2)(p12q13), are likely to be either derived from a common ancestor or to have subtly different breakpoints. Presumably the lack of selection against most inversions allows them to accumulate and disperse amongst different populations over time.


Spatial mapping and size distribution of oxidative potential of particulate matter released by spatially disaggregated sources.
The ability of particulate matter (PM) to induce oxidative stress is frequently estimated by acellular oxidative potential (OP) assays, such as ascorbic acid (AA) and 1,4-dithiothreitol (DTT), used as proxy of reactive oxygen species (ROS) generation in biological systems, and particle-bound ROS measurement, such as 2',7'-dichlorodihydrofluorescein (DCFH) assay. In this study, we evaluated the spatial and size distribution of OP results obtained by three OP assays (OPAA, OPDCFH and OPDTT), to qualitative identify the relative relevance of single source contributions in building up OP values and to map the PM potential to induce oxidative stress in living organisms. To this aim, AA, DCFH and DTT assays were applied to size-segregated PM samples, collected by low-pressure cascade impactors, and to PM10 samples collected at 23 different sampling sites (about 1 km between each other) in Terni, an urban and industrial hot-spot of Central Italy, by using recently developed high spatial resolution samplers of PM, which worked in parallel during three monitoring periods (February, April and December 2017). The sampling sites were chosen for representing the main spatially disaggregated sources of PM (vehicular traffic, rail network, domestic heating, power plant for waste treatment, steel plant) present in the study area. The obtained results clearly showed a very different sensitivity of the three assays toward each local PM source. OPAA was particularly sensitive toward coarse particles released from the railway, OPDCFH was sensible to fine particles released from the steel plant and domestic biomass heating, and OPDTT was quite selectively sensitive toward the fine fraction of PM released by industrial and biomass burning sources.


Targeted mutation of key residues at the start of helix 12 in the hERalpha ligand-binding domain identifies the role of hydrogen-bonding and hydrophobic interactions in the activity of the protein.
Estradiol (E(2)) and tamoxifen exert their effects through two members of the nuclear receptor superfamily, estrogen receptor (ER)-alpha and -beta. We want to identify the key interactions linking ligand-binding and activity of the ERalpha. Asp-351 and Leu-536 participate in hydrogen bond (Asp-351) and hydrophobic (Leu-536) interactions at the start of helix 12 in the ligand-binding domain (LBD) of the ERalpha. Mutations at each position alter ER activity, but we do not know which is more important. We mutated these residues in combination and individually and assessed the activity of the mutated ERs in the absence and presence of E(2) and 4-OHT on an ERE-driven and an AP-1-driven promoter, as well as their ability to interact with coregulators. On an ERE-driven promoter, the residue at position 351 determined whether E(2) stimulated or reduced the activity of the ER, as well as the level of activity in the presence of 4-OHT. Surprisingly, mutation of both residues generally did not produce cumulative deleterious effects, and they exerted counterbalancing effects on the basal activity on both promoters. Our results identify the contributions of specific interactions to the activity of the hERalpha, and support the concept that this region couples ligand-binding with ER activity.


Ebselen inhibits contractile responses of guinea-pig parenchymal lung strips.
Ebselen is a new anti-inflammatory drug with a wide spectrum of pharmacological activities. Since this compound might be useful in diseases related to airway inflammation we evaluated the effects of ebselen on the contractile responses of guinea-pig parenchymal lung strip. Ebselen and its sulfur analogue RP 62373 depressed both histamine H1-receptor-mediated and KCl-induced (50 mM) contractions of guinea-pig lung strips equipotently. The responses to histamine were only affected via depression of the maximal response; treatment with 3 microM ebselen for 30 min resulted in depression to 77 +/- 5% of the control value, whereas 10 and 30 microM inhibited the contractions to 53 +/- 4 and 52 +/- 4% of the control value respectively. The responses after membrane depolarisation (50 mM KCl) were less sensitive to ebselen pretreatment; 10 microM ebselen inhibited contractions by only 20%, whereas 30 and 100 microM depressed the response by approximately 50%. These observations were evaluated in the context of the activities of ebselen already described. The effects of lipoxygenase, cyclooxygenase, protein kinase C inhibition and thiol alkylation were studied, using established agents. However, although interaction with critical thiol groups might explain our data, the mode of action of ebselen is yet not fully elucidated.


Low-intensity Extracorporeal Shock Wave Therapy for Erectile Dysfunction: A Systematic Review and Meta-analysis.
To assess the efficacy of low-energy extracorporeal shock wave therapy (LI-ESWT) for erectile dysfunction (ED), a systematic review and meta-analysis was undertaken. A comprehensive search of the PubMed, Cochrane Register, and Embase databases to March 2017 was performed for randomized controlled trials reporting on patients with ED treated with LI-ESWT. The International Index of Erectile Function (IIEF) and the Erection Hardness Score (EHS) were the most commonly used tools to evaluate the therapeutic efficacy of LI-ESWT. There were 9 studies including 637 patients from 2005 to 2017. The meta-analysis revealed that LI-ESWT could significantly improve IIEF (mean difference [MD]: 2.54; 95% confidence interval [CI], 0.83-4.25; P = .004) and EHS (risk difference [RD]: 0.16; 95% CI, 0.03-0.28; P = .01). Therapeutic efficacy could last at least 3 months (MD: 4.15; 95% CI, 1.40-6.90; P = .003). Lower energy density (0.09 mJ/mm2, MD: 4.14; 95% CI, 0.87-7.42; P = .01) increased the number of pulses (3000 pulses per treatment, MD: 5.11; 95% CI, 3.18-7.05, P < .0001) and shorter total treatment courses (<6 weeks, MD: 3.73; 95% CI, 0.54-6.93; P = .02) resulted in better therapeutic efficacy. These studies suggest that LI-ESWT could significantly improve the IIEF and EHS of patients with ED. The publication of robust evidence from additional randomized controlled trials and longer-term follow-up would provide more confidence regarding the use of LI-ESWT for patients with ED.


Predictors of Medicare costs in elderly beneficiaries with breast, colorectal, lung, or prostate cancer.
Determining the apportionment of costs of cancer care and identifying factors that predict costs are important for planning ethical resource allocation for cancer care, especially in markets where managed care has grown. This study linked tumor registry data with Medicare administrative claims to determine the costs of care for breast, colorectal, lung and prostate cancers during the initial year subsequent to diagnosis, and to develop models to identify factors predicting costs. Patients with a diagnosis of breast (n = 1,952), colorectal (n = 2,563), lung (n = 3,331) or prostate cancer (n = 3,179) diagnosed from 1985 through 1988. The average costs during the initial treatment period were $12,141 (s.d. = $10,434) for breast cancer, $24,910 (s.d. = $14,870) for colorectal cancer, $21,351 (s.d. = $14,813) for lung cancer, and $14,361 (s.d. = $11,216) for prostate cancer. Using least squares regression analysis, factors significantly associated with cost included comorbidity, hospital length of stay, type of therapy, and ZIP level income for all four cancer sites. Access to health care resources was variably associated with costs of care. Total R2 ranged from 38% (prostate) to 49% (breast). The prediction error for the regression models ranged from < 1% to 4%, by cancer site. Linking administrative claims with state tumor registry data can accurately predict costs of cancer care during the first year subsequent to diagnosis for cancer patients. Regression models using both data sources may be useful to health plans and providers and in determining appropriate prospective reimbursement for cancer, particularly with increasing HMO penetration and decreased ability to capture complete and accurate utilization and cost data on this population.


Sophisticated and naïve listeners' magnitude estimation scaling judgments of speech intelligibility and speech annoyance.
15 women with formal training in speech and hearing sciences and 15 women with no formal training provided magnitude estimation scaling responses for the intelligibility and annoyance of audiotaped speech samples. Analysis indicated that both groups scaled intelligibility and annoyance the same. As samples became more unintelligible, they also became more annoying.


Resonance Raman scattering-infrared absorption dual-mode immunosensing for carcinoembryonic antigen based on ZnO@SiO2 nanocomposites.
Detection of cancer biomarkers is crucial for the diagnosis and monitoring of malignant tumors. However, the accuracy and sensitivity still require sufficient improvement for practically clinical application. In this work, a reliable and sensitive dual-mode immunosensing method is described for carcinoembryonic antigen (CEA) detection using a biofunctional ZnO@SiO2 nanocomposite as a resonance Raman scattering (RRS)-infrared (IR) absorption nanoprobe. The multiphonon RRS signal originating from the ZnO and the characteristic IR fingerprint signal of the transverse optical and longitudinal optical phonon modes of the asymmetric stretching of Si-O-Si bonds showed no interference with each other. A CEA antibodies-immobilized substrate was fabricated to capture the analyte/nanoprobe complexes. The RRS intensity at 569 cm‒1 and the IR absorption at 1061 cm‒1 were used for quantitative analysis. Accurate CEA detection was performed as a result of the strong resistance of the dual-mode nanoprobe to surrounding interference. The limit of detection was 98.0 fg mL‒1. The detection range was 500 ng mL‒1 - 50 fg mL‒1, which is wider than those of single-mode RRS or IR absorption immunosensings. High reproducibility, selectivity and specificity were achieved. The assay performance of human serum samples demonstrated the practicability of the method in clinical cancer diagnosis.


The effect of endogenous opioids on blood pressure during stress.
1. A series of experiments were conducted to investigate the effect of endogenous opioids on blood pressure of laboratory rats during stress. 2. Rats subjected to 120 min immobilization showed a significant drop in systolic pressure which could be prevented by pretreatment injections of naloxone. 3. Adrenalectomized rats subjected to the same kind of stress showed a drop in systolic pressure equivalent to only 30% of the systolic pressure drop in the intact animals. This decrease in systolic pressure could also be prevented by pretreatment injections of naloxone. 4. It was concluded that the decrease in systolic pressure in intact rats during immobilization was mostly due to endogenous opioids released from the adrenal glands, whereas opioids of other origins such as the pituitary gland, were also important.


Reliability Evaluation of the New AO Spine-DGOU Classification for Osteoporotic Thoracolumbar Fractures.
To perform an interobserver and intraobserver agreement evaluation of the new AO Spine-DGOU classification system for osteoporotic thoracolumbar fractures (OFc). Complete imaging studies of 97 patients (radiographs, computed tomography scans, and magnetic resonance imaging) with osteoporotic thoracolumbar fractures were selected and classified using the OFc by 6 spine surgeons (3 senior surgeons with more than 15 years of experience and 3 surgeons with less than 15 years). After a 4-week interval, the same cases were presented to the same evaluators in a random sequence for a new classification assessment. The weighted kappa coefficient (wκ) was used to determine the interobserver and intraobserver agreement. The interobserver agreement was moderate, wκ = 0.59 (95% confidence interval 0.54-0.64). The intraobserver agreement was fair, wκ = 0.35 (95% confidence interval 0.29-0.40). Interobserver agreement slightly improved for junior staff between first and second evaluation, suggesting a learning effect. Better agreement was obtained by senior staff at the interobserver and intraobserver agreement. This independent assessment demonstrated that new OFc allows moderate interobserver agreement and fair intraobserver agreement. Further studies are necessary prior to its widespread adoption.


Analytics and visualization tools to characterize single-cell stochasticity using bacterial single-cell movie cytometry data.
Time-lapse microscopy live-cell imaging is essential for studying the evolution of bacterial communities at single-cell resolution. It allows capturing detailed information about the morphology, gene expression, and spatial characteristics of individual cells at every time instance of the imaging experiment. The image analysis of bacterial "single-cell movies" (videos) generates big data in the form of multidimensional time series of measured bacterial attributes. If properly analyzed, these datasets can help us decipher the bacterial communities' growth dynamics and identify the sources and potential functional role of intra- and inter-subpopulation heterogeneity. Recent research has highlighted the importance of investigating the role of biological "noise" in gene regulation, cell growth, cell division, etc. Single-cell analytics of complex single-cell movie datasets, capturing the interaction of multiple micro-colonies with thousands of cells, can shed light on essential phenomena for human health, such as the competition of pathogens and benign microbiome cells, the emergence of dormant cells ("persisters"), the formation of biofilms under different stress conditions, etc. However, highly accurate and automated bacterial bioimage analysis and single-cell analytics methods remain elusive, even though they are required before we can routinely exploit the plethora of data that single-cell movies generate. We present visualization and single-cell analytics using R (ViSCAR), a set of methods and corresponding functions, to visually explore and correlate single-cell attributes generated from the image processing of complex bacterial single-cell movies. They can be used to model and visualize the spatiotemporal evolution of attributes at different levels of the microbial community organization (i.e., cell population, colony, generation, etc.), to discover possible epigenetic information transfer across cell generations, infer mathematical and statistical models describing various stochastic phenomena (e.g., cell growth, cell division), and even identify and auto-correct errors introduced unavoidably during the bioimage analysis of a dense movie with thousands of overcrowded cells in the microscope's field of view. ViSCAR empowers researchers to capture and characterize the stochasticity, uncover the mechanisms leading to cellular phenotypes of interest, and decipher a large heterogeneous microbial communities' dynamic behavior. ViSCAR source code is available from GitLab at https://gitlab.com/ManolakosLab/viscar .


Improvement of aminolevulinic acid (ALA)-mediated photodynamic diagnosis using n-propyl gallate.
Photodynamic diagnosis (PDD) using aminolevulinic acid (ALA) is widely used in clinical fields. In PDD, protoporphyrin IX (PpIX) is generated from ALA in tumors, allowing the detection of the tumors by PpIX fluorescence. However, it is well known that PpIX is bleached by light irradiation (photobleaching) resulting in reduced PDD efficiency. In this study, n-propyl gallate (NPG) was investigated as an enhancer of PDD efficiency. Tumor cells were incubated with NPG after treatment with ALA, and reactive oxygen species and PpIX fluorescence were measured. The antioxidant NPG suppressed the production of reactive oxygen species from light-irradiated porphyrins and ameliorated photobleaching of PpIX generated from ALA in vitro and in vivo. Incubation with NPG decreased the production of reactive oxygen species from PpIX and suppressed PpIX photobleaching. These results indicate that the antioxidant NPG may significantly improve PDD efficiency.


MRI predictors of revision surgery after primary lumbar discectomy.
The prognostic significance of preoperative MRI findings in patients undergoing discectomy is incompletely understood. Identifying the radiological predictors of revision surgery on pre-operative MRI can guide management decisions and potentially prevent multiple surgeries. We included 181 patients who underwent primary lumbar discectomy between 2010 and 2014. All patients were contacted via a short telephone interview to determine if they had revision surgery within 5 years of their index surgery. Preoperative MRI of the lumbosacral spine was evaluated for various radiological factors including type of disc herniation, anatomical location of herniation, direction of herniation, degree of disc degeneration, end plate changes and presence of listhesis. Other potential confounders including age, gender, smoking status and index level of surgery were also recorded. Multivariate model of all radiological predictors and confounders were developed and a step-wise approach was used to remove insignificant variables in order to develop final significant multivariate model. P value of <0.05 was considered statistically significant. Patients with retrolisthesis were found to be 2.7 times more likely than the patients without listhesis to require revision surgery (p = 0.019). Patients with foraminal disc herniation were 3.45 times more likely than the patients with paramedian disc herniation to require revision surgery (p = 0.026). Other MRI predictors failed to achieve statistical significance. Based on the data presented patients with retrolisthesis and/or foraminal disc herniation should be counselled on the relatively higher risk of revision surgery when proceeding with discectomy, or alternative options should be considered.


Variation in number of general practitioner consultations before hospital referral for cancer: findings from the 2010 National Cancer Patient Experience Survey in England.
Information from patient surveys can help to identify patient groups and cancers with the greatest potential for improvement in the experience and timeliness of cancer diagnosis. We aimed to examine variation in the number of pre-referral consultations with a general practitioner between patients with different cancers and sociodemographic characteristics. We analysed data from 41,299 patients with 24 different cancers who took part in the 2010 National Cancer Patient Experience Survey in England. We examined variation in the number of general practitioner consultations with cancer symptoms before hospital referral to diagnose cancer. Logistic regression was used to identify independent predictors of three or more pre-referral consultations, adjusting for cancer type, age, sex, deprivation quintile, and ethnic group. We identified wide variation between cancer types in the proportion of patients who had visited their general practitioner three or more times before hospital referral (7·4% [625 of 8408] for breast cancer and 10·1% [113 of 1124] for melanoma; 41·3% [193 of 467] for pancreatic cancer and 50·6% [939 of 1854] for multiple myeloma). In multivariable analysis, with patients with rectal cancer as the reference group, those with subsequent diagnosis of multiple myeloma (odds ratio [OR] 3·42, 95% CI 3·01-3·90), pancreatic cancer (2·35, 1·91-2·88), stomach cancer (1·96, 1·65-2·34), and lung cancer (1·68, 1·48-1·90) were more likely to have had three or more pre-referral consultations; conversely patients with subsequent diagnosis of breast cancer (0·19; 0·17-0·22), melanoma (0·34, 0·27-0·43), testicular cancer (0·47, 0·33-0·67), and endometrial cancer (0·59, 0·49-0·71) were more likely to have been referred to hospital after only one or two consultations. The probability of three or more pre-referral consultations was greater in young patients (OR for patients aged 16-24 years vs 65-74 years 2·12, 95% CI 1·63-2·75; p<0·0001), those from ethnic minorities (OR for Asian vs white 1·73, 1·45-2·08; p<0·0001; OR for black vs white 1·83, 1·51-2·23; p<0·0001), and women (OR for women vs men 1·28, 1·21-1·36; p<0·0001). We identified strong evidence of interactions between cancer type and age group and sex (p<0·0001 for both), and between age and ethnicity (p=0·0013). The model including these interactions showed a particularly strong sex effect for bladder cancer (OR for women vs men 2·31, 95% CI 1·98-2·69) and no apparent ethnic group differences in young patients aged 16-24 years, whilst the only cancers without an apparent age gradient were testicular cancer and mesothelioma. Our findings could help to prioritise and stratify early diagnosis initiatives and research, focusing on patients with cancers and sociodemographic characteristics with the largest potential for improvement. None.


Urban ecophysiology: beyond costs, stress and biomarkers.
Natural habitats are rapidly declining due to urbanisation, with a concomitant decline in biodiversity in highly urbanised areas. Yet thousands of different species have colonised urban environments. These organisms are exposed to novel urban conditions, which are sometimes beneficial, but most often challenging, such as increased ambient temperature, chemicals, noise and light pollution, dietary alterations and disturbance by humans. Given the fundamental role of physiological responses in coping with such conditions, certain physiological systems such as the redox system, metabolism and hormones are thought to specifically influence organisms' ability to persist and cope with urbanisation. However, these physiological systems often show mixed responses to urbanisation. Does this mean that some individuals, populations or species are resilient to the urban environmental challenges? Or is something missing from our analyses, leading us to erroneous conclusions regarding the impact of urbanisation? To understand the impact of urbanisation, I argue that a more integrated mechanistic and ecological approach is needed, along with experiments, in order to fully understand the physiological responses; without knowledge of their ecological and evolutionary context, physiological measures alone can be misinterpreted. Furthermore, we need to further investigate the causes of and capacity for individual plasticity in order to understand not only the impact of urbanisation, but also species resilience. I argue that abiotic and biotic urban factors can interact (e.g. pollution with micro- and macronutrients) to either constrain or relax individual physiological responses - and, thereby, plasticity - on a temporal and/or spatial scale, which can lead to erroneous conclusions regarding the impact of urbanisation.


Chemosensor for the optical detection of aliphatic amines and diamines.
Two new chemosensor dyes with either one or two trifluoroacetophenone recognition moieties have been investigated in terms of reversibly interacting with amines and diamines.


Loss of SR-A and CD36 activity reduces atherosclerotic lesion complexity without abrogating foam cell formation in hyperlipidemic mice.
The scavenger receptors SR-A and CD36 have been implicated in macrophage foam cell formation during atherogenesis and in the regulation of inflammatory signaling pathways, including those leading to lesional macrophage apoptosis and plaque necrosis. To test the impact of deleting these receptors, we generated Apoe(-/-) mice lacking both SR-A and CD36 and fed them a Western diet for 12 weeks. We analyzed atheroma in mice, assessing lesion size, foam cell formation, inflammatory gene expression, apoptosis, and necrotic core formation. Aortic root atherosclerosis in Apoe(-/-)Cd36(-/-)Msr1(-/-) mice, as assessed by morphometry, electron microscopy, and immunohistochemistry, showed no decrease in lesion area or in vivo foam cell formation when compared to Apoe(-/-) mice. However, Apoe(-/-)Cd36(-/-)Msr1(-/-) lesions showed reduced expression of inflammatory genes and morphological analysis revealed a approximately 30% decrease in macrophage apoptosis and a striking approximately 50% decrease in plaque necrosis in aortic root lesions of these mice. Although targeted deletion of SR-A and CD36 does not abrogate macrophage foam cell formation or substantially reduce atherosclerotic lesion area in Apoe(-/-) mice, loss of these pathways does reduce progression to more advanced necrotic lesions. These data suggest that targeted inhibition of these pathways in vivo may reduce lesional inflammation and promote plaque stability.


A facile approach for sulphur and nitrogen co-doped carbon nanodots to improve photothermal eradication of drug-resistant bacteria.
In this study, we produced S, N co-doped CNDs (SN@CNDs) by using dimethyl sulfoxide (DMSO) and formamide (FA) as single sources of S and N, respectively. We varied the S/N ratios by adjusting the volume ratios of DMSO and FA and investigated their effect on the red-shift of the CNDs' absorption peak. Our findings demonstrate that SN@CNDs synthesized using a volume ratio of 5:6 between DMSO and FA exhibit the most significant absorption peak redshift and enhanced near-infrared absorption performance. Based on comparative analysis of the particle size, surface charge, and fluorescence spectrum of the S@CNDs, N@CNDs, and SN@CNDs, we propose a possible mechanism to explain the change of optical properties of CNDs due to S, N doping. Co-doping creates a more uniform and smaller band gap, resulting in a shift of the Fermi level and a change in energy dissipation from radioactive to non-radiative decay. Importantly, the as-prepared SN@CNDs exhibited a photothermal conversion efficiency of 51.36% at 808 nm and demonstrated exceptional photokilling effects against drug-resistant bacteria in both in vitro and in vivo experiments. Our facile method for synthesizing S and N co-doped CNDs can be extended to the preparation of other S and N co-doped nanomaterials, potentially improving their performance.


Intermediate trophoblast: a distinctive form of trophoblast with specific morphological, biochemical and functional features.
Morphological and immunohistochemical analysis of placental tissue from 12 days to term using antibodies directed against the unique carboxyl terminal peptide of human chorionic gonadotrophin beta subunit, human placental lactogen (hPL) and pregnancy-specific beta I-glycoprotein reveals that an intermediate form of trophoblast with distinctive features exists. This cell has a diverse morphological expression and is located overlying chorionic villi, in the trophoblastic columns, basal plate and the trophoblastic shell. Although all three placental proteins are localized in this cell the predominant hormone is hPL, which can serve as an immunocytochemical marker. One of the primary functions of this cell is in implantation and in the establishment of the uteroplacental circulation since it extensively invades the spiral arteries at the placental site. It is proposed that this distinctive form of trophoblast be termed 'intermediate trophoblast'.


Synthesis and iNOS inhibitory activities of thioflavones.
A number of thioflavones has been synthesized and evaluated for their iNOS inhibitory activities. Thiowogonin (6) was obtained from naturally occurring chrysin in 5 steps. Other thioflavones were prepared from the corresponding flavones in a single step by the reaction with Lawesson's reagent. The biological activities of thioflavones were not enhanced by the functional group conversion from carbonyl to thiocarbonyl. Compounds 11 and 13 showed potent NO inhibitory activity at high concentration (40 uM), leading to the possible development of novel neuroprotective agents based on wogonin.