Biological activity and photocatalytic properties of a naphthyl-imidazo phenanthroline (HNAIP) ligand and its [Ir(ppy)2(HNAIP)]Cl and [Rh(ppy)2(HNAIP)]Cl complexes.
The synthesized 2-(hydroxy-1-naphtyl)imidazo-[4,5-f][1,10]phenanthroline (HNAIP) ligand and its new iridium ([Ir(ppy)2(HNAIP)]Cl) and rhodium ([Rh(ppy)2(HNAIP)]Cl) complexes, being ppy = 2-phenylpiridinate, show cytotoxic effects in SW480 (colon adenocarcinoma) and A549 (epithelial lung adenocarcinoma) cells. They all are cytotoxic in the tested cell lines. HNAIP and [Rh(ppy)2(HNAIP)]+ are the most cytotoxic, whereas [Ir(ppy)2(HNAIP)]+ displays negligible cytotoxicity towards A549 cells and moderate activity towards SW480. The interaction of all three compounds with Bovine Serum Albumin (BSA), l-glutathione reduced (GSH), nicotinamide adenine dinucleotide (NADH) and DNA was studied to explain the differences found in terms of cytotoxicity. None of them are able to interact with BSA, thus excluding bioavailability due to plasma protein interaction as the possible differentiating factor in their biological activity. By contrast, small differences have been observed regarding DNA interaction. In addition, taking advantage of the emission properties of these molecules, they have been visualized in the cytoplasmic region of A549 cells. Inductively coupled plasma mass spectrometry (ICP-MS) experiments show, in turn, that the internalization ability follow the sequence [Rh(ppy)2(HNAIP)]+ > [Ir(ppy)2(HNAIP)]+ > cisplatin. Therefore, it seems clear that the cellular uptake by tumour cells is the key factor affecting the different cytotoxicity of the metal complexes and that this cellular uptake is influenced by the hydrophobicity of the studied complexes. On the other hand, preliminary catalytic experiments performed on the photo-oxidation of GSH and some amino acids such as l-methionine (Met), l-cysteine (Cys) and l-tryptophan (Trp) provide evidence for the photocatalytic activity of the Ir(III) complex in this type of reactions.


Anoestrous conditions in the mare, their diagnosis and treatment.
The condition of anoestrus in the mare is described and the various causes of this syndrome are discussed. A regimen for examining systematically the clinically anoestrus mare is proposed, and methods of treatment are suggested.


Differential regulation of pituitary adenylate cyclase-activating peptide receptor variants in the rat suprachiasmatic nucleus.
Pituitary adenylate cyclase-activating peptide is densely distributed in the suprachiasmatic nucleus, which functions as the circadian pacemaker. A receptor for pituitary adenylate cyclase-activating peptide, denoted as PAC(1), exists in six variant forms. We used reverse transcriptase-polymerase chain reaction to identify the PAC(1) variants that are expressed in the suprachiasmatic nucleus. Dominant variant forms of PAC(1) in the suprachiasmatic nucleus were PAC(1)short, PAC(1)hip, and PAC(1)hop1. By in situ hybridization, we examined 24-h profiles of mRNAs for the identified receptor variants in the suprachiasmatic nucleus in constant darkness and during the light-dark cycle. In constant darkness there were clear circadian rhythms in PAC(1)short mRNA with a peak at circadian time 4 but no rhythmicity was observed in PAC(1)hip mRNA or PAC(1)hop1 mRNA. In light-dark cycles, on the other hand, PAC(1)hip mRNA displayed a bimodal rhythm with troughs at zeitgeber time 4 and 16 but PAC(1)hop1 mRNA stayed constant during the day. These results suggest that PAC(1) splice variants are differentially regulated in the rat suprachiasmatic nucleus.


Top-down self-regulation processes as determinants of oral hygiene self-care behaviour: A systematic scoping review.
Understanding the psychological mechanisms that moderate oral hygiene self-care behavior is anticipated to benefit efforts to change such behavior. Top-down self-regulatory (TSR) processes represent one group of relatively unexplored, yet potentially influential, moderating factors. This systematic scoping review aims to explore whether there is evidence that TSR processes moderate oral hygiene self-care engagement within the current literature. CINAHL, The Cochrane Library, Embase, MEDLINE, PsycINFO, Scopus, and Web of Science databases were searched up to April 2020 for articles that compared measures of TSR processes (such as self-monitoring, inhibitory control, and task switching) to oral hygiene self-care behavior, or tested interventions that aimed to change or support TSR processes. The search returned 6626 articles, with 25 included in the final sample. Weak evidence supported both the role of TSR processes as moderators of interdental cleaning and the value of interventions targeting self-monitoring of interdental cleaning behavior. Overall, methodological limitations rendered the findings somewhat inconclusive, with an absence of objective assessments of TSR capacity, and little focus on TSR processes as moderators of intervention effects. The inconclusive, but reasonably promising, findings point to the value of continuing to apply TSR processes within studies of oral hygiene behavior. Exploring why interdental cleaning appears more reliant on TSR processes than toothbrushing, employing objective neuropsychological assessment, and measuring TSR constructs within interventions targeting TSR processes, are encouraged. As a scoping review, the study hopes to generate interest and serve as a starting point for further investigation.


Elective hepatic resection.
Significant salvage of patients with a wide variety of cysts and benign tumors of the liver and of some patients with biliary strictures can be achieved by hepatic resection in carefully selected clinical situations with a low operative mortality rate and an acceptable postoperative complication rate. Still to be determined is the role of hepatic resection in metastatic carcinoma and sarcoma of the liver, where survival is modest but measurable, but important palliation can be achieved. Hepatomas should be resected when possible, but hepatic resection for aid in resection of bile duct carcinoma has proved generally unrewarding.


Homicide or suicide? Xylophagia: a possible explanation for extraordinary autopsy findings.
Determining the cause of death and differentiating self-inflicted injuries from non-self-inflicted injuries is a primary goal in legal medicine. Especially with unidentified decedents, autopsy findings alone are often not sufficient; there is no knowledge of pre-existing conditions and only circumstantial evidence is available from the scene of death. In our case, radiological, histological, and toxicological examinations provided an explanatory model for extraordinary autopsy findings consistent with pica, a rare eating disorder. In cases of pica, variable and potentially lethal complications emerge, depending on the type and amount of material ingested. Our case is of an apparently uncontrolled intake of wooden objects (xylophagia). The resulting mechanical damage to the gastrointestinal tract and subsequent soft tissue damage supports that this behavioral disorder is not only of medical concern, but also identifies it as a mental disease with medico-legal relevance.


Development of a sensitive phospho-p70 S6 kinase ELISA to quantify mTOR proliferation signal inhibition.
Drug blood levels can only serve as a surrogate because of the lack of information on the drug's direct pharmacological effects in the individual patient. Measurement of the mammalian target of rapamycin (mTOR) activity dependent on the phosphorylation status of p70 S6 kinase (p70 S6K) offers a practical way for monitoring pharmacodynamic drug activity, with the potential to better assess the state of immunosuppression in individual patients. Here, we established a novel in vitro model system by treating Jurkat cells and peripheral blood mononuclear cells with different concentrations of sirolimus after stimulation with phorbol 12-myristate 13-acetate. A dose-dependent reduction of the p70 S6K phosphorylation status was demonstrated by Western blot and a newly established enzyme-linked immunosorbent assay (ELISA). Relative phospho-p70 S6K values from ELISA and relative densities from Western blot analysis in peripheral blood mononuclear cells revealed a strong correlation (Spearman correlation coefficient r s = 0.7, P = 0.01). Finally, parallel assays confirmed a sirolimus dose-dependent reduction of cytokine production and cell proliferation in the in vitro model. Pharmacodynamic monitoring of mTOR inhibition with a p70 S6K ELISA could guide mTOR inhibitor immunosuppression therapy toward a more individualized therapy. The usage of this technique now has to be evaluated in a clinical series of patients.


Learning on the run - a qualitative, longitudinal study of pharmacy educators' experiences implementing a hospital pharmacy residency program.
A hospital pharmacy foundation residency training program has been introduced in Australia, modelled on residency programs established in other countries. The program aims to support the professional development of early-career hospital pharmacists, in both clinical and non-clinical roles. Pharmacy educators are usually tasked with the implementation and maintenance of this program. This qualitative, longitudinal study aimed to investigate hospital pharmacy educators' expectations, perceptions and experiences with implementing and developing their residency program. Qualitative data were collected at two timepoints, approximately 24 months apart, using either focus groups or interviews with pharmacy educators who were directly involved in the implementation of the residency program at their respective hospitals. During the early phases of implementation, and approximately 24 months later, participants were asked about their experiences and expectations of the residency program as well as any changes that had occurred within the residency program over time. Four focus groups and three semi-structured interviews were held with pharmacy educators and senior pharmacists from different hospital settings. These were audio recorded and transcribed verbatim. Transcripts were inductively analysed via thematic analysis. Fifteen hospital pharmacy educators and senior hospital pharmacists participated in the initial focus groups and interviews, and seven educators were retained for follow-up. Four main themes were established from the discussions: participants had great expectations of a positive impact of the residency on their workplace and residents' professional development; substantial effort, support and resources were needed to implement and maintain a residency program; self-motivation and engagement is needed by residents to succeed and experience timely completion and career acceleration; and lastly a balance between standardisation, consistency and flexibility in delivering the residency needs to be found. The role of educators changed with the implementation of a residency, with the addition of more managerial and supervisory aspects. The Australian hospital pharmacy foundation residency program is a complex workplace training program with multiple factors and prerequisites influencing its implementation, development and outcomes. Pharmacy educators are central to the successful implementation and ongoing sustainability of a residency program. They may benefit from formal training and qualifications to support their role.


Comparative analysis of estrogen receptors covalently labeled with an estrogen and an antiestrogen in several estrogen target cells as studied by limited proteolysis.
Estrogen receptors covalently labeled with the estrogen affinity label [3H]ketononestrol aziridine (KNA) or with the antiestrogen affinity label [3H]tamoxifen aziridine (TAZ) were subjected to limited proteolysis with trypsin, alpha-chymotrypsin, and Staphylococcus aureus V8 protease and then analyzed on 10-20% sodium dodecyl sulfate-polyacrylamide gradient gels followed by fluorography. The similar molecular weights of intact receptors (Mr 66,000 daltons) and the proteolytic digest patterns indicate extensive homology among estrogen receptors from MCF-7 human breast cancer cells, GH4 rat pituitary cells and rat uterus when liganded with estrogen or antiestrogen. Each protease generated a distinctive ladder of estrogen receptor fragments, and the fragmentation patterns were virtually identical for estrogen receptors labeled with estrogen (KNA) or antiestrogen (TAZ). Each protease yielded a relatively "resistant" receptor fragment of about 28,000-35,000 daltons. Trypsin and chymotrypsin at higher concentrations generated a much smaller 6,000-8,000 dalton digest product that still contained the [3H]KNA- or [3H]TAZ-labeled receptor binding site. Moreover, the receptor digest patterns were similar for estrogen receptors from the three different target cells. Our studies suggest considerable structural relatedness among these three estrogen receptors and also indicate that these two affinity labels bind to a similar, perhaps identical, region of the receptor molecule.


The relative partitioning of neutral and ionised compounds in sodium dodecyl sulfate micelles measured by micellar electrokinetic capillary chromatography.
The rational use of micelles in quantitative structure-activity and quantitative structure-permeation relationships implies a good knowledge of the nature of recognition forces underlying solute-micelle association. The aims of this study were to unravel the intermolecular interaction forces responsible for the association of neutral and ionised compounds with negatively charged sodium dodecyl sulfate (SDS) micelles, using micellar electrokinetic capillary chromatography (MEKC). The MEKC capacity factors (log k(MEKC)) of 36 neutral model solutes were analysed by linear solvation free-energy relationships (LSERs). The results indicate that the size and H-bond acceptor strength of solutes are mainly responsible for their MEKC retention. Compared to n-octanol, the SDS micelles are more cohesive and stronger H-bond donors. Strong attractive electrostatic interactions govern solute-micelle association for positively charged compounds and micelles of the opposite charge, whereas repulsive electrostatic interactions occur between negatively charged solutes and micelles of the same charge. The capacity factors measured for the ionised forms of the acids and bases under study (log k(MEKC)(I)) indeed lie on two distinct plateau, about -1.0 for the former and about 2.0 for the latter and depend on the solute's charge more than on its chemical structure. Thus, the derivation of a diff(log k(MEKC)(N-I)) value, defined as the difference between the log k(MEKC) values of the neutral and charged species, strongly correlates with the respective log k(MEKC)(N) value and does not afford additional information.


Lateral lid lysis for medial lid and medial canthus lacerations.
Techniques are now being used to provide adequate healing time for medial lid and medial canthal full-thickness lacerations. Lateral upper and lower lid lysis allows the needed extended period of healing.


Measuring quality of life in PSP: the PSP-QoL.
To develop a new patient-reported outcome measure for progressive supranuclear palsy (PSP) and to test its psychometric properties. First, the authors generated a pool of potential scale items from in-depth patient interviews. Second, the authors administered these items, in the form of a questionnaire, to a sample of people with PSP and traditional psychometric methods were used to develop a rating scale satisfying standard criteria for reliability and validity. Third, the authors examined the psychometric properties of the rating scale in a second sample. In stage 1, a pool of 87 items was generated from 27 patient interviews. In stage 2, a scale with two subscales (physical, 22 items; mental, 23 items), satisfying standard criteria for reliability and validity, was developed from the response data of 225 patients with PSP. In stage 3, the scale was examined in 188 people with PSP. Missing data were low, scores in both subscales were evenly distributed, floor and ceiling effects were small. Reliability was high (Cronbach's alpha 0.93, 0.95; test-retest 0.95, 0.92). Validity was supported by the interscale intercorrelation (0.60), factor analysis, and the magnitude and pattern of correlations with four other rating scales, disease severity, and disease duration. The psychometric properties of the new scale were similar in the United Kingdom and North America, and in clinic- and community-based samples studied. The Progressive Supranuclear Palsy Quality of Life scale (PSP-QoL) may be a helpful patient-reported scale for clinical trials and studies in PSP.


A simple method for assessment of glomerular size and its use in the study of kidneys in acromegaly and compensatory renal enlargement.
As measurement of absolute glomerular size is difficult we developed a method of assessing glomerular size that was simple and practical and could be used to compare the kidneys in different groups of patients. Using a semi-automatic image analyser, the cross-sectional area of 100 randomly-selected glomeruli, outlined by Bowman's capsule, was measured on sections of kidneys taken at necropsy. The mean of the logarithms of the largest 25 areas was calculated. The method was applied to compare control kidneys (53) with the kidneys in acromegalics (20), in patients with one kidney (10) and in patients with asymmetrical kidneys (12). Kidneys were heavier in the three test groups than in controls. Glomerular sizes were similar in controls and in acromegalics but were larger in single and disparate kidneys. There was a relationship between glomerular size and kidney weight within the control group and across the four groups taken together. This only partly accounted for the observed differences in glomerular size between the groups. Histological comparison of the acromegalic and single kidneys showed more global glomerulosclerosis in single kidneys and also segmental lesions, mainly at the glomerular hilum, only in the single kidneys. These findings show that renal enlargement occurs in acromegaly and in single and disparate kidneys but is accompanied by markedly different glomerular features. This implies different mechanisms for the renal enlargement. The method of assessing glomerular size is useful in the study of these and other conditions affecting the kidney.


A trial of the utilization of stable isotope analysis for the estimation of the geographic origins of unidentified cadavers.
The number of unidentified cadavers is increasing worldwide and the effective methods which reveal their geographic origin are not well known. In this study, we analyzed the urine stable isotope ratio of hydrogen and oxygen collected from three locations: Chiba (Japan), Fuzhou (China), and Denpasar (Indonesia) from healthy volunteers. In addition, analysis of the effect of drinking bottled water on stable isotope ratios found in urine, and the comparison of the stable isotope ratios of urine and saliva, were conducted. Statistically significant differences in δ(2)H and δ(18)O values from the three locations were found. In this pilot study, urine δ(18)O values became increasingly similar to those of bottled drinking water during an eight-day period of drinking only bottled water. In a separate pilot study significant differences in δ(18)O, δ(13)C, and δ(15)N values from urine and saliva were found, but not in δ(2)H values. In all three studies, although the number of samples was limited, the results suggest that with further research, stable isotope analysis from urine samples might be used to identify the origins of unidentified corpses, assist in determining the length of time an individual has been in a given area and distinguish between body fluids.


Color discrimination impairment in workers exposed to mercury vapor.
To study color discrimination impairment in workers exposed to elemental mercury (Hg) vapor. Twenty-four male workers from a chloralkali plant exposed to Hg vapor, aged 42+/-9.8 years, duration of exposure 14.7+/-9.7 years, were examined. The 8h TWA air-borne Hg concentration in workplace was 59 microg/m(3); mean Hg urinary excretion (HgU) was 20.5+/-19.3 microg/g creatinine; mean Hg urinary excretion after the administration of a chelating agent, sodium 2,3-dimercapto-1-propane-sulfonate (DMPS), was 751.9+/-648 microg/48h. Twenty-four age- and gender-matched control subjects were compared. Visual acuity, alcohol intake, smoking habits, and history of diseases or drugs potentially influencing color vision were registered. The Lanthony 15-Hue desaturated test (L-D15-d) was used to assess color vision. The results were expressed quantitatively as Bowman's Color Confusion Index (CCI), and qualitatively according to Verriest's classification of acquired dyschromatopsias. The CCI was significantly higher in the exposed group than in the control (mean CCI 1.15 versus 1.04; P=0.04). The proportion of subjects with errorless performance on the Lanthony test was significantly lower in the Hg exposed group compared to referents (52% versus 73%; P=0.035). The exposed group showed higher frequency of type III dyschromatopsias (blue-yellow confusion axis) in comparison with the control group (12.5% versus 8.3%), however, the difference did not reach statistical significance. Multiple regression did not show any significant relationship between the CCI, and age, alcohol consumption, or measures of exposure. In agreement with previous studies by Cavalleri et al. [Toxicol. Lett. 77 (1995) 351; Environ. Res. Sec. A 77 (1998) 173], the results of this study support the hypothesis that exposure to mercury vapor can induce sub-clinical color vision impairment. This effect was observed at an exposure level below the current biological limit for occupational exposure to mercury. This raises doubts on the actual protection afforded by this limit concerning the effect of mercury on color vision.


Availability and components of maternity services according to providers and users perspectives in North Gondar, Northwest Ethiopia.
The goal of reducing maternal mortality can be achieved when women receive important service components at the time of their maternity care. This study attempted to assess the availability and the components of maternity services according to the perspectives of service users and providers. A linked facility and population-based survey was conducted over three months (January to March 2012) in North Gondar Zone. Twelve kebeles (clusters) were selected randomly from six districts to identify maternity clients cared for by skilled providers. Then 12 health centers and 3 hospitals utilized by the corresponding cluster population were selected for facility survey. Interview with facility managers/heads, providers and clients and observations were used for data collection. Data were entered using Epi Info and were exported to SPSS software for analysis. Antenatal and delivery care were available in most of the visited facilities. However, the majority of them were not fully functioning for EmOC according to their level. Signal functions including administration of anticonvulsants and assisted vaginal delivery were missing in seven and five of the 12 health centers, respectively. Only one hospital met the criteria for comprehensive emergency obstetric care (performed cesarean section). Only 24% of the providers used partograph consistently. About 538 (32.3%) and 231 (13.8%) of the women received antenatal and delivery care from skilled providers, respectively. Most of the services were at health centers by nurses/midwives. At the time of the antenatal care, women received the important components of the services (percentage of users in bracket) like blood pressure checkup (79%), urine testing (35%), tetanus immunization (45%), iron supplementation (64%), birth preparedness counseling (51%) and HIV testing (71%). During delivery, 80% had their blood pressure measured, 78% were informed on labor progress, 89% had auscultation of fetal heartbeat, 80% took drugs to prevent bleeding and 78% had counseling on early & exclusive breast-feeding. Antenatal and delivery care were available in most of the visited facilities. However, important components of both the routine and emergency maternity care services were incomplete. Improving the functional capacity of health facilities for the delivery of routine maternity and EmOC services are needed.


Osteoarthritis year in review 2018: genetics and epigenetics.
This review was designed to identify highlights of the osteoarthritis (OA) genetics and epigenetics literature published between April 2017 and January 2018. A Pubmed literature search was conducted using the keywords 'osteoarthritis' and each of the following: 'genomic', 'genetic', 'epigenomic', 'epigenetic', 'histone', 'noncoding RNA', 'miRNA', 'lncRNA', 'DNA methylation', 'DNA hydroxymethylation', 'DNMT', and 'TET'. The dates of publication were restricted to 4/1/2017-1/15/2018. Results were compared to the same search terms limited to 4/1/2016-1/15/2017. Virtually all search term combinations demonstrated a decrease in papers published this year compared to last, with epigenetic and miRNA/lncRNA research being stable. Despite this, numerous advances were made this year, including the second large genome-wide association study (GWAS) study of hand OA, a new twin study of hip and knee OA concordance, an extensive study of GDF5 evolution, analyses of the contribution of Dnmt3a to OA, a description of DNA methylation in a nonhuman primate model of OA, and an integrated, multi-omics analysis of DNA methylation, mRNA, and protein expression in human OA samples, among others. A variety of micro- and a few circular-RNA studies were also published, highlighting the importance of noncoding RNA in both the pathogenesis and potential treatment of OA. Although publications have decreased slightly in the last year, genetics and epigenetics continue to be a topic of substantial research in OA, and considerable progress continues to be made in the field.


Heterogeneity of serum, egg amylase and egg lysozyme in the interspecific hybrids of ducks.
Polymorphism of serum and egg amylase by means of horizontal agarose gel electrophoresis and egg lysozyme by means of horizontal starch gel electrophoresis in Pekin, Muscovy ducks and their interspecific hybrids was studied. In the interspecific hybrids of ducks the codominant type of heredity of serum, egg yolk and egg white amylase isozymes, as well as egg white lysozyme, were found.


Properties of glutathione peroxidase isolated from human plasma.
Human plasma glutathione peroxidase (GPx) was purified to homogeneity by ammonium sulfate fractionation, gel filtration on Sephadex G-150, chromatography on DEAE Sephacel, chromatofocusing with polybuffer, and gel filtration with Sephadex G-75. This isolation resulted in about 5,400-fold purification of the enzyme with a 32% yield in enzyme activity. The final preparation had a specific activity of about 28 units (mmoles NADPH oxidized) per milligram of protein. Determination of selenium on the purified enzyme revealed a content of 3.8 g atoms per mole GPx. Gel electrophoresis using SDS with standard proteins revealed a molecular weight of about 23,000 for the subunits, which would indicate a molecular weight of about 92,000 for the native enzyme. Amino acid analyses of the purified GPx indicated aspartate, glutamate, proline, glycine, alanine, and leucine as the predominant amino acids and cysteine, methionine, tryptophan, and histidine as the minor amino acids.


Different resistance of mammalian red blood cells to hemolysis by bile salts.
To evaluate why hemolysis of red blood cells (RBC) by bile acids varies in different mammalian species, we determined the mean corpuscular volume (MCV), lipid content and the concentrations of the conjugates of deoxycholate and of NaCl inducing 50% hemolysis of RBC from healthy humans, pigs, horses, cows, sheep and jaundiced humans. A volume of 0.05 mL of washed RBC at 1% hematocrit, which has the same lipid content but different phospholipid composition and number of erythrocytes (owing to the variable MCV), was incubated in taurodeoxycholate (TDC) solution (0-5 mM) to determine the TDC concentration inducing 50% hemolysis (TDC50). The TDC50 was highest in RBC of sheep and decreased within the series sheep > pig > cow > horse > healthy human > jaundiced human, which have generally increasing MCV. The osmotic resistance followed an inverse order, with jaundiced human > healthy human > horse > cow > pig > sheep. Although we found no correlation between the TDC50 and phospholipid composition of the erythrocytes tested, the extent of bile salt-induced hemolysis seemed to depend on both the MCV and the number of erythrocytes in the incubation medium.


Resectability of Peritoneal Carcinomatosis: Learnings from a Prospective Cohort of 533 Consecutive Patients Selected for Cytoreductive Surgery.
The aim of this study was to identify the risk factors and causes of unresectability in a large cohort of patients with peritoneal carcinomatosis (PC) selected for cytoreductive surgery (CRS), and to assess the contribution of the different imaging modalities to the patient-selection process. The pre- and intraoperative data of 533 consecutive patients with PC planned for CRS at a single institution were reviewed. All patients underwent computed tomography (CT) magnetic resonance imaging and/or positron emission tomography/CT within the 2 days prior to surgery. Among the 533 patients, 436 (82 %) underwent complete CRS, 86 (16 %) underwent exploratory laparotomy without CRS because of multiple small-bowel involvement (n = 31), invasion of different digestive segments (n = 15), an elevated PC index (n = 14), invasion of the mesenteric root (n = 12), or another cause (n = 14), and 11 (2 %) did not undergo laparotomy because of disease progression on preoperative imaging findings. On univariate analysis, elevated levels of tumor markers and a short delay between the last cycle of chemotherapy and the scheduled surgery were identified as predictors of unresectability for the colonic PC population, while a younger age was identified in patients with gastric PC. Multivariate analysis disclosed the use of neoadjuvant chemotherapy and a younger age as independent predictors of unresectability in the colonic PC population. The current modalities for the assessment of PC resectability, including functional imaging examinations, have a low impact on patient selection for CRS. New tools are needed to decrease the rate of open-close procedures.


Hypertension and COVID-19: Potential use of beta-blockers and a call for randomized evidence.
Hypertension is one of the most common morbidities in COVID-19. Previous studies demonstrated that hypertension increases composite poor outcomes in patients with COVID-19. Beta-blockers is widely used as one of the most common antihypertensive agents. Beta-blockers may hold potential benefits in COVID-19 treatment, with current evidence of the potential mechanism of beta-blockers remains scarce. However, several mechanisms were suggested, including decreasing RAAS pathway activity and lowering the ACE2 levels, reducing cytokine storms, and may be beneficial in reducing mortality in ARDS related COVID-19. Further large-scale randomized clinical trials should be conducted before a definite recommendation can be drawn.


Desmopressin--a nontransfusional form of prevention of postextractive bleeding in some patients with von Willebrand's type I disease. Case report.
In this article the possibility of using the Minirin (desmopressin) in maxillofacial surgery in person with hemostatic disorders has been described. The our case of patient with von Willebrand's disease type I indicates that this drug is very effective in bleeding after teeth extractions.


Increased Prevalence of Malignancies in Fibrous Dysplasia/McCune-Albright Syndrome (FD/MAS): Data from a National Referral Center and the Dutch National Pathology Registry (PALGA).
Malignant transformation of fibrous dysplasia lesions has been reported in patients with fibrous dysplasia/McCune-Albright syndrome (FD/MAS). Recently, we have observed an increased risk for breast cancer. In this study, the prevalence of skeletal and extraskeletal malignancies in patients with FD/MAS in the Netherlands was assessed by analyzing data from our cohort of FD/MAS patients, the Dutch Pathology Registry (PALGA), and the Netherlands Cancer Registry (NCR). We extracted data on sex, age at diagnosis of FD/MAS, type of FD/MAS, type of malignancy, and age at diagnosis of malignancy and histology of bone and malignant tissue when available, including GNAS-mutation analysis from patients' medical records. Standardized Morbidity Ratios (SMRs) with 95% confidence intervals were calculated. Twelve malignancies were identified in the LUMC FD/MAS cohort and 100 in the PALGA cohort. In this cohort, SMR was increased for osteosarcoma (19.7, 95% CI 3.5-48.9), cervical cancer (4.93, 95%CI 1.7-8.2), thyroid cancer (3.71, 95% CI 1.1-7.8), prostate cancer (3.08, 95% CI 1.8-4.6), and melanoma (2.01, 95%CI 1.2-3.1). SMRs for pancreatic cancer or hepatocellular carcinoma could not be calculated due to low numbers. The small number of malignancies identified in our FD/MAS cohort precluded the calculation of SMRs for our cohort specifically. Our findings show that patients with FD/MAS appear to have an increased risk for osteosarcoma, cervical, thyroid, and prostate cancer and melanoma. However, these data should be interpreted with caution, as true incidence rates of the identified malignancies may be influenced by the inclusion of only patients with histologically confirmed FD/MAS. The etiology of this increased risk for malignancies still needs to be elucidated.


Sensitivity of human peripheral blood mononuclear leukocytes to visible light.
Overnight light exposure of cultured human peripheral blood mononuclear leukocytes [PBML], significantly increased basal [3H]thymidine incorporation and upon stimulation with phytohemagglutinin [PHA]. Melatonin (10(-9) to 10(-5) M) enhanced the light-induced increase of [3H]thymidine incorporation, while serotonin (10(-9) to 10(-7) M) stimulated [3H]thymidine incorporation in the dark. The wavelengths responsible of this effect were restricted to the blue-green zone of the spectrum. The stimulatory effect of visible light on PHA-induced DNA replication had a circannual rhythm, being maximal during winter. In winter, white light also reduced melatonin and serotonin binding to PBML membranes and switched the PBML indole metabolism towards serotonin and 5-hydroxy-indole-acetic acid [HIAA] synthesis, with a concomitant decrease of melatonin production.


Cardiovascular disease risk factors among undergraduate medical students in a tertiary care centre of eastern India: a pilot study.
Handful studies report the prevalence of cardiovascular disease (CVD) risk factors among medical students from India and none from the eastern part of the country. To estimate the prevalence of risk factors of CVD and their correlation with CVD risk ratio among the MBBS students from eastern India. 433 students were studied. International Physical Activity Questionnaire-long form was used for assessment of physical activity and Perceived Stress Scale (PSS) to elicit psychological stress levels. Waist-to-height ratio (WHtR) was calculated. Total cholesterol to high-density lipoprotein ratio was calculated as the CVD risk ratio. 39.3% were women and 68.6% of the subjects were in junior classes. 22.4% subjects had high PSS while 30% performed low physical activity. Tobacco and alcohol intake was prevalent in 29.3% and 21.0% respectively. High CVD risk ratio was found in 14.3%. Most risk factors were more prevalent among juniors except diabetes. Among the non-overweight and non-obese subjects there was a significant positive correlation between WHtR and CVD risk score (R = 0.33, p < 0.001). 82.7% of the variance in CVD risk ratio could be explained by WHtR, Body mass index, Triglycerides and Low-density lipoprotein (F(7, 425) = 296.085), of which LDL (β = 0.755) contributed the most. High prevalence of different modifiable CVD risk factors revealed among the subjects in this study is concerning. WHtR appears promising as an independent early predictor of CVD risk in Indian population. A dedicated CVD risk assessment tool for the young population is necessary.


Salt-dependent hemagglutination with Bunyaviridae antigens.
Hemagglutination titers of antigens from nine serologic groups of Bunyaviridae were increased by hypertonic NaCl. The effect was predominantly on sonically treated antigens and was additive with the increase from sonic treatment alone.


Woodruff's plexus-arterial or venous?
Woodruff's plexus is a vascular network located on the posterior lateral wall of the inferior meatus of the nasal cavity and it is generally considered to be responsible for posterior epistaxis. Despite being initially identified in 1949 as a venous plexus, discrepancies exist within literature regarding this anatomical structure, particularly its arterial or venous nature and its association with posterior epistaxis. This systematic review aims to collate information pertaining to Woodruff's plexus and evaluate our current understanding of this vascular area. The systematic review was performed using published data in PubMed, Google Scholar, Scopus, EBSCO and Web of Science platforms using keywords such as 'Woodruff', 'posterior' and 'plexus'. Articles referring to Woodruff's plexus were collected and analysed by independent reviewers. The search revealed 154 papers, out of which only 40 were included in the review. Out of this number only two papers were anatomical dissection studies, both of which identify the plexus as venous in nature. Seventeen studies describe the plexus as venous by citing these two papers. The remainder of the articles (23) consider Woodruff's plexus as arterial with variability in the reported arteries that supply it. Woodruff's original description of a venous plexus is supported by modern anatomical studies. There are a multitude of reports that Woodruff's plexus is arterial in nature, despite the absence of existing anatomical studies to support this notion. This misconception has likely arisen due to clinical associations in relation to posterior epistaxis.


Examining the behaviour of energy prices to COVID-19 uncertainty: A quantile on quantile approach.
The energy market is extremely vulnerable to the uncertainty caused by the pandemic and leads to global lockdowns and stagnant economic activity. This study is important because energy prices (EPs) experience a dramatic decline due to the pandemic, which has negative consequences for the global economy. We aim to analyze EPs behaviour to coronavirus (COVID-19) from 2020:01 to 2021:05. The finding shows that EPs are extremely vulnerable to the uncertainty produced by the pandemic in the short run. The COVID-19 has a negative effect on EPs in the medium to upper quantile, which suggests that higher uncertainty caused by the pandemic results in rapid decline. However, the impact of the COVID-19 is greater on the oil prices (OPs) as compared to the natural gas (NGP) and the heating oil price (HOP). Moreover, the finding reveals that COVID-19 impact on EPs are consistently negative across all the quantile. The degree of the impact increases when the relationship changes from short to long run. The pandemic has affected the energy price in the short run, which needs prudent policies to fully grasp the magnitude of the COVID-19 impact on energy prices.


Transcriptome analysis reveals the molecular mechanisms by which carbon dots regulate the growth of Chlamydomonas reinhardtii.
Carbon dots (CDs) have attracted increasing attention for their ability to artificially improve photosynthesis. Microalgal bioproducts have emerged as promising sources of sustainable nutrition and energy. However, the gene regulation mechanism of CDs on microalgae remains unexplored. The study synthesized red-emitting CDs and applied them to Chlamydomonas reinhardtii. Results showed that 0.5 mg/L-CDs acted as light supplements to promote cell division and biomass in C. reinhardtii. CDs improved the energy transfer of PS II, photochemical efficiency of PS II, and photosynthetic electron transfer. The pigment content and carbohydrate production slightly increased, while protein and lipid contents significantly increased (by 28.4% and 27.7%, respectively) in a short cultivation time. Transcriptome analysis identified 1166 differentially expressed genes. CDs resulted in faster cell growth by up-regulating the expression of genes associated with cell growth and death, promoting sister chromatid separation, accelerating the mitotic process and shortening the cell cycle. CDs improved the ability of energy conversion by up-regulating photosynthetic electron transfer-related genes. Carbohydrate metabolism-related genes were regulated and provided more available pyruvate for the citrate cycle. The study provides evidence for the genetic regulation of microalgal bioresources by artificially synthesized CDs.


Predictive factors of academic success in neuromusculoskeletal anatomy among doctor of physical therapy students.
Predictors of academic success in anatomy have been studied, but not in Doctor of Physical Therapy (DPT) students. The objectives of this study were to (1) explore predictors of academic success in a DPT anatomy course, (2) evaluate sex-based differences in the predictors of academic success and their influence on anatomy course grade, and (3) investigate the influence of the DPT anatomy course on visual-spatial ability. Forty-nine DPT students completed a demographic questionnaire, Learning and Study Strategies Inventory (LASSI), and Mental Rotations Test (MRT) before the ten-week anatomy course (MRT-1) and repeated the MRT at the end of the course (MRT-2). Anatomy course grade was determined based on quizzes and written and practical examinations. Multiple regression analysis showed significant associations between the predictor variables age (p = 0.010) and the LASSI anxiety subscale (p = 0.017), which measures anxiety coping, with the anatomy course grade. On the MRT-1, male DPT students attempted and correctly answered more questions than females (both, p < 0.0001). Female students had higher LASSI self-regulation and use of academic resources subscale scores (both, p < 0.05). In the 44 DPT students that completed the MRT-2, the number of correct and attempted responses increased following the anatomy course (p < 0.0001). Age and anxiety coping, but not sex, are predictors of anatomy course grades in DPT students. Mental rotations test scores improved following the anatomy course. The LASSI should be used in other cohorts to identify students with low anxiety subscale scores in order to provide targeted support.


The vertical birthing position of the Trobrianders, Papua New Guinea.
During an ethnomedical field study the author succeeded in participating and photographing 4 traditional birthgivings among the Trobrianders/Papua New Guinea. Their various vertical postures are described with special reference to specific Trobriand practices and discussed by literature review. The results suggest that vertical birthing positions are advantageous to horizontal ones and should be reconsidered by modern Western obstetrics.


EPR studies on the anaerobic reduction of fungal laccase. Evidence for participation of type 2 copper in the reduction mechanism.
1. In anaerobic reduction studies on fungal laccase B (p-diphenol:O2 oxidoreductase, EC 22.214.171.124) with the EPR and stopped-flow techniques it was found that the type 2 copper of the enzyme is rapidly undergoing a reduction-oxidation cycle which is followed by a slower reduction in a couple of seconds. An intermediate EPR signal of unknown origin is formed in the same time-range as the initial reduction of type 2 copper and disappears again when this copper ion is reoxidized. 2. The rate of the anaerobic reoxidation of type 2 copper is similar to the reduction rate of the two-electron acceptor, suggesting that they are interacting in the electron transfer of the enzyme. 3. The changes in the reaction rates of both type 2 and type 3 copper appear to be affected in a similar way by changes in pH. 4. The EPR signal of the type 2 Cu2+ suggests that this ion is liganded to one or more nitrogens.


Comparison of estimated renal net acid excretion from dietary intake and body size with urine pH.
The aim of this study was to examine whether estimated net acid excretion (NAE) from two dietary assessment instruments can predict urine pH in healthy volunteers. The Observing Protein and Energy Nutrition (OPEN) study, which was designed to assess dietary measurement error, included men and women aged 40 to 69 years. Participants were asked to complete two food frequency questionnaires (FFQs) and two 24-hour recalls at approximately three-month intervals, and to return two 24-hour urine samples during the same period. NAE was estimated using a previously described equation. The estimates obtained from the different dietary assessment measures were correlated with actual urine pH. Four hundred eighty-four subjects were enrolled in the OPEN study. All participants were included in this study on urine pH, given that they had all completed at least one dietary assessment and one urine sample. The study took place in Montgomery County, MD, between September 1999 and March 2000. Correlation coefficients between NAE estimates using the FFQ data and the average of two urine pH measures were -0.34 and -0.39 for women and men, respectively. Removing within-person variance in the urine pH levels resulted in a deattenuated overall correlation of -0.50 for the FFQ. Correlations between the 24-hour recall estimates of NAE were -0.41 and -0.32 for women and men, respectively. For the 24-hour recalls, the deattenuated overall correlation was -0.50. Our findings suggest that FFQs provide adequate dietary data to estimate renal NAE and could be used as a surrogate for urinary pH levels in large epidemiologic studies.


Favipiravir can evoke lethal mutagenesis and extinction of foot-and-mouth disease virus.
Antiviral agents are increasingly considered an option for veterinary medicine. An understanding of their mechanism of activity is important to plan their administration either as monotherapy or in combination with other agents. Previous studies have shown that the broad spectrum antiviral agent favipiravir (T-705) and its derivatives T-1105 and T-1106 are efficient inhibitors of foot-and-mouth disease virus (FMDV) replication in cell culture and in vivo. However, no mechanism for their activity against FMDV has been proposed. In the present study we show that favipiravir (T-705) can act as a lethal mutagen for FMDV in cell culture. Evidence includes virus extinction associated with increase in mutation frequency in the mutant spectrum of 860 residues of the 3D (polymerase)-coding region, and a decrease of specific infectivity while the consensus nucleotide sequence of the region analyzed remained invariant. The mutational spectrum evoked by favipiravir differs from that observed with other viruses in that no predominant transition type is observed, indicating that a movement towards A,U- or G,C-rich regions of sequence space is not a prerequisite for virus extinction. We discuss prospects for the use of favipiravir to assist in the control of FMDV, and its possible broader use in veterinary medicine as an extension of its current status as antiviral agent for human influenza virus.


Ab initio protein structure prediction.
Steady progress has been made in the field of ab initio protein folding. A variety of methods now allow the prediction of low-resolution structures of small proteins or protein fragments up to approximately 100 amino acid residues in length. Such low-resolution structures may be sufficient for the functional annotation of protein sequences on a genome-wide scale. Although no consistently reliable algorithm is currently available, the essential challenges to developing a general theory or approach to protein structure prediction are better understood. The energy landscapes resulting from the structure prediction algorithms are only partially funneled to the native state of the protein. This review focuses on two areas of recent advances in ab initio structure prediction-improvements in the energy functions and strategies to search the caldera region of the energy landscapes.


Red cell metabolic and membrane features in haemolytic anaemia of alcoholic liver disease (Zieve's syndrome).
Zieve's syndrome (ZS), which consists of transient haemolytic anaemia, jaundice, hyperlipoproteinaemia, and alcohol-induced liver disease, was studied in male patients during the acute (n = 20) and the remittent (n = 10) phase. Chronic alcoholics (n = 10) without haemolysis and healthy male persons (n = 10) served as controls. Erythrocytes were separated into old and young cells by means of density-layer centrifugation. Those fractions which contained older red cells disclosed a pyruvate-kinase instability which resulted in impaired metabolism. Changes in membrane lipid composition as indicated by increased cholesterol and polyunsaturated fatty acids (PUFA) were also detected in patients during the acute phase of ZS. Alcohol-induced red-cell vitamin-E deficiency with a decrease in PUFA levels may provoke an oxidation of reduced red-cell glutathione which in turn results in the enzyme instability. This study lends further support to the hypothesis that the putative role of the red-cell metabolic injury in the origin of haemolysis in ZS cannot be envisaged without introducing membrane-linked and extracellular cofactors.


[Surgical treatment of invasive tumors of the nasal cavity and paranasal sinuses involving the inferior and middle cranial fossae].
An analysis of combined treatment of 11 patients with tumors of the paranasal sinuses involving the skull base was made. Radical surgical interventions were performed in the volume of nasal exenteration, maxillectomy and orbital exenteration, nasal exenteration, and total maxillectomy. The technique of surgical interventions and results of treatment are described.


Correlations between EEG changes induced by diazepam and the localization of epileptic spikes and seizures.
We evaluated the EEG reaction to an intravenous injection of diazepam as an additional tool in difficult localization problems in epilepsy. The normal reaction to diazepam being an increase in beta activity, it was assumed that a poor increase indicated an abnormal region. This method was tested in 21 epileptic patients having chronically implanted intracerebral electrodes. Beta activity before and after injection was quantified by spectral analysis; increases were compared in homologous contralateral channels. In 12 of the 21 cases the area of poorest response to diazepam was identical to that of seizure onset. In 7 cases, there was some overlap between the area of poorest diazepam response and that of seizure onset, but they did not exactly coincide. In two cases there was no overlap between the two areas. Agreement was slightly higher when comparing diazepam response and area of highest interictal spike activity. This procedure is simple and without risk, particularly compared to the thiopental injection which is used for the same purpose. It is helpful in determining abnormal areas when localization information from various diagnostic sources are conflicting. Even when the epileptic focus is well defined, it can point to other poorly functioning areas.


Are sleep studies necessary in COPD?
While there are many research questions still requiring performance of research sleep studies in patients with COPD, their use is not advocated in routine clinical practice, except in patients who have symptoms of the sleep apnoea/hypopnoea syndrome or possibly in those without daytime hypoxaemia (PaO2 greater than 60 mmHg) who have marked polycythaemia or marked cor pulmonale.


Optical effect of resin cement, abutment material, and ceramic thickness on the final shade of CAD-CAM ceramic restorations.
High-translucency ceramics can be influenced by the underlying structure, altering the restoration shade. How this affects color matching is unclear. The purpose of this in vitro study was to investigate the optical effects of cement shade, ceramic type, ceramic thickness, and abutment material on the final color of computer-aided design and computer-aided manufacturing (CAD-CAM) ceramic restorations. Two shades of resin cement (yellow, translucent), 3 types of background (titanium, white zirconia, yellow zirconia), and 3 types of high-translucent ceramic (each type shade A1 and A3) were used in this study. For the experimental groups, a total of 72 ceramic specimens were produced across 4 groups based on ceramic thickness (1.0 mm, 1.5 mm, and 2.0 mm). For the control groups, each ceramic type and shade was prepared at a thickness of 4 mm. A total of 8 resin cement specimens were produced in 4 groups based on shade by using a plastic mold (12×12×0.2 mm). To demonstrate the effect of implant abutment materials, 3 types of background were fabricated with a thickness of 2 mm. For the experimental groups, 3 specimens (ceramic, cement, and background) were sequentially placed with glycerin in the center of each background specimen. Color measurements of the experimental groups were made with a spectrophotometer and recorded in the Commission Internationale de l'Eclairage Lab coordinate system. The color differences (ΔE) between experimental and control groups were then calculated. The Kruskal-Wallis test (α=.05) was used to analyze the multiple comparisons of ceramic thickness, ceramic type, and abutment material. The Mann-Whitney U test (α=.05) was used to analyze cement shade. Significant differences were found for different ceramic thicknesses, ceramics types, and abutment materials (P≤.001). A clinically acceptable shade (ΔE≤3) was found in 1.5- and 2.0-mm ceramics with the titanium and 2.0-mm ceramics with the yellow zirconia background. However, the color between the experimental group and the control group was similar when using the 2 cement shades (P>.05). An increase in ceramic thickness could minimize alteration of the final shade. High-translucency ceramics, together with a resin cement, were able to successfully mask titanium with a ceramic thickness of at least 1.5 mm. However, only a ceramic with a thickness of 2.0 mm was able to mask the yellow zirconia background.


Insulin-like growth factor-1 and insulin-like growth factor binding protein-1 and 3 in the follicular fluid of infertile patients submitted to in vitro fertilization.
In the present article we propose to evaluate IGF-1, IGFBP-1 and 3 in the follicular fluid of infertile patients submitted to in vitro fertilization. We performed a case-control study with 53 infertile patients submitted to the first in vitro fertilization attempt. We compared their follicular fluid concentration of IGF-1, IGFBP-1 and IGFBP-3 between the patients who became pregnant (n = 11) versus those nonpregnant (n = 42). The clinical characteristics of patients from the two groups were similar in terms of age and body mass index. Data related to the analysis of ovulation induction was not different regarding length of induction in days, number of retrieved oocytes, fertilization rate, and number of transferred embryos. Furthermore, the number of FSH units required for ovarian induction was also similar between the studied groups. IGF-1 and IGFBP-1 were not significantly different between the groups (p > 0.05). However, those patients that became pregnant presented a lower follicular fluid concentration of IGFBP-3, 2237.10 +/- 582.73 pg/ml and 2657.64 +/- 584.15 ng/ml, respectively (p = 0.038). We demonstrated an association of a lower follicular fluid IGFBP-3 in individuals that became pregnant compared to subjects that did not after in vitro fertilization.


Maillard reaction-like lysine modification by a lipid peroxidation product: immunochemical detection of protein-bound 2-hydroxyheptanal in vivo.
2-Hydroxyheptanal (2-HH) is one of the reactive aldehyde species generated during the peroxidation of n-6 polyunsaturated fatty acids, such as linoleic and arachidonic acids. Analogous to the Maillard reaction of reducing sugars, 2-HH readily reacts with lysine epsilon-amino groups. In the present study, to define the occurrence of the Maillard reaction-like lysine modification by 2-HH in vivo, we raised a monoclonal antibody directed to a trihydropyridinone (THPO) structure, 1-alkyl-4-butyl-5-pentyl-1,2,6-trihydropyridin-3-one, formed from 2-HH and lysine, and examined the presence of the antigenic structure in the human atherosclerotic aorta. Mice were immunized with the 2-HH-modified keyhole limpet hemocyanin (KLH) as the immunogen. Using a THPO-carrier protein conjugate, we screened the hybridomas and finally obtained a clone that produced the monoclonal antibody 3C8 (mAb3C8). The antibody strongly recognized bovine serum albumin (BSA) treated with 2-HH, but showed no cross-reactivity with BSAs modified with other related aldehydes. By using this antibody, it was revealed that the antigenic structure was indeed present in atherosclerotic lesions of the human aorta.


Hybridization boosters diversification in a Neotropical Bulbophyllum (Orchidaceae) group.
Genetic data shows that cryptic hybrids are more common than previously thought and that hybridization and introgression are widespread processes. Regardless, studies on hybridization are scarce for the highly speciose Bulbophyllum. The genus presents more than 2,200 species and many examples of recent radiations, in which hybridization is expected to be frequent. Currently, only four natural Bulbophyllum hybrids are recognized, all of them recently described based on morphological evidence. Here we test whether genomic evidence supports the hybrid status of two Neotropical Bulbophyllum species, while also evaluating the impact of this phenomenon on the genomes of the putative parental species. We also assess if there is evidence of hybridization among B. involutum and B. exaltatum, sister species that diverged recently. We leverage the power of next-generation sequence data, associated with model-based analysis for three systems putatively constituted by two parental species and one hybrid. All taxa belong to the Neotropical B. sect. Didactyle clade. We found evidence of hybridization in all studied systems. Despite the occurrence of hybridization, there are no signs of backcrossing. Because of the high propensity of hybridization across many taxa, the common occurrence of hybridization during the evolutionary history of B. sect. Didactyle means it is time to account for and examine its evolutionary role in these orchids.


Arterio-venous fetoplacental vascular geometry and hemodynamics in the mouse placenta.
The fetoplacental vasculature network is essential for the exchange of nutrients, gases and wastes with the maternal circulation and for normal fetal development. The present study quantitatively compares arterial and venous morphological and functional differences in the mouse fetoplacental vascular network. High resolution X-ray micro-computed tomography was used to visualize the 3D geometry of the arterial and venous fetoplacental vasculature in embryonic day 15.5 CD-1 mice (n = 5). Automated image analysis was used to measure the vascular geometry of the approximately 4100 arterial segments and 3200 venous segments per specimen to simulate blood flow through these networks. Both the arterial and venous trees demonstrated a hierarchical branching structure with 8 or 9 (arterial) or 8 (venous) orders. The venous tree was smaller in volume and overall dimensions than the arterial tree. Venous vessel diameters increased more rapidly than arteries with each successive order, leading to lower overall resistance, although the umbilical vein was notably smaller and of higher resistance than these scaling relationships would predict. Simulation of blood flow for these vascular networks showed that 57% of total resistance resides in the umbilical artery and arterial tree, 17% in the capillary bed, and 26% in the venous tree and umbilical vein. A detailed examination of the mouse fetoplacental arterial and venous tree revealed features, such as the distribution of resistance and the dimension of the venous tree, that were both morphologically distinct from other vascular beds and that appeared adapted to the specialized requirements of sustaining a fetus.


Hairy cell leukemia: a B-lymphocytic disorder derived from splenic marginal zone lymphocytes?
Although there is increasing evidence that the majority of cases of hairy cell leukemia represent B-lymphoproliferative disorders, the exact subset of B-cells from which hairy cells are derived, is still unclear. On the basis of results obtained in previous studies, and data collected from the literature, it is suggested that B-lymphocytes normally residing in the marginal zone of the splenic white pulp (so called 'marginal zone lymphocytes') represent the cell type from which B-lineage derived hairy cells originate.


New polynuclear 1,5-naphthyridine-silver(I) complexes as potential antimicrobial agents: The key role of the nature of donor coordinated to the metal center.
New polynuclear silver(I) complexes with 1,5-naphthyridine (1,5-naph), [Ag(NO3)(1,5-naph)]n (Ag1), [Ag(CF3COO)(1,5-naph)]n (Ag2) and [Ag(CF3SO3)(1,5-naph)]n (Ag3) were synthesized by the reaction of the corresponding silver(I) salt and 1,5-naph in ethanol at room temperature. These complexes were characterized by NMR, IR and UV-Vis spectroscopy, while their crystal structures were determined by single-crystal X-ray diffraction analysis. In all these complexes, 1,5-naph acts as a bridging ligand between two Ag(I) ions, while the remaining coordination sites are occupied by oxygen atom(s) of the corresponding anion. The antimicrobial efficiency of these silver(I) complexes was evaluated against the broad panel of Gram-positive and Gram-negative bacteria and fungi. The complexes showed good to moderate antibacterial activity with the minimal inhibitory concentration (MIC) values being in the range 2.5-100 μg/mL (6.5-333.3 μM), while their antifungal activity against the investigated Candida spp. was significantly higher (MIC = 0.78-6.25 μg/mL; 2.6-20.8 μM). Moreover, complexes Ag1 and Ag2 effectively inhibited C. albicans biofilms formation, while Ag1 was also shown to inhibit the formation of mixed C. albicans/Pseudomonas aeruginosa biofilms. Toxicological evaluations on zebrafish (Danio rerio) embryos revealed that all silver(I) complexes could be applied as antifungal agents, whereas Ag3 had the best therapeutic potential showing both the lowest MIC values against the tested Candida strains and the non-toxic in vivo response in the zebrafish embryos at these doses.


Advantages and disadvantages of PET and SPECT in a busy clinical practice.
The continued high utilization of rest-stress single-photon emission computed tomographic (SPECT) myocardial perfusion imaging (MPI) is supported by its known clinical benefits, established reimbursement, and wide availability of cameras and radiopharmaceuticals. However, traditional rest-stress SPECT protocols tend to be lengthy and inefficient, and the prevalence of equivocal studies continues to be a problem. The use of stress-only SPECT protocols in selected patients, and a new generation of ultrafast SPECT cameras have led to improved image quality, reduced dosimetry and shorter, more efficient MPI protocols. The utilization of positron emission tomographic (PET) MPI has been accelerated by the availability of radiopharmaceuticals that can be generated on-site, and by the availability of more PET cameras. Emerging evidence consistently demonstrates that PET provides improved image quality, greater interpretive certainty, higher diagnostic accuracy, lower patient dosimetry, and shorter imaging protocols as compared to SPECT. Importantly, PET imaging allows assessment of left ventricular function at peak-stress, and evaluation of microvascular function through the measurement of absolute myocardial blood flow at rest and at peak-stress. Wider utilization of PET MPI is hindered by a high cost of entry, high on-going costs, and an immature reimbursement structure.


Nuclear receptors and transcriptional regulation in non-alcoholic fatty liver disease.
As a result of a sedentary lifestyle and excess food consumption in modern society, non-alcoholic fatty liver disease (NAFLD) characterized by fat accumulation in the liver is becoming a major disease burden. Non-alcoholic steatohepatitis (NASH) is an advanced form of NAFLD characterized by inflammation and fibrosis that can lead to hepatocellular carcinoma and liver failure. Nuclear receptors (NRs) are a family of ligand-regulated transcription factors that closely control multiple aspects of metabolism. Their transcriptional activity is modulated by various ligands, including hormones and lipids. NRs serve as potential pharmacological targets for NAFLD/NASH and other metabolic diseases. In this review, we provide a comprehensive overview of NRs that have been studied in the context of NAFLD/NASH with a focus on their transcriptional regulation, function in preclinical models, and studies of their clinical utility. The transcriptional regulation of NRs is context-dependent. During the dynamic progression of NAFLD/NASH, NRs play diverse roles in multiple organs and different cell types in the liver, which highlights the necessity of targeting NRs in a stage-specific and cell-type-specific manner to enhance the efficacy and safety of treatment methods.


An educational program for parents of asthmatic preschool children: short- and medium-term effects.
Parent education has proven to be effective in improving parents coping with their child's asthma. Little is known about its effectiveness neither during inpatient rehabilitation nor about the different effectiveness of different approaches. A controlled clinical trial was conducted with 242 parents of asthmatic children aged less than 8 years. The aims were to develop a cognitive-behavioral training program for parents and compare its differential effectiveness with an information-centered standard-program as part of rehabilitation. Both groups reported a highly significant increase in their knowledge, self-efficacy and quality of life over time in a follow-up just after the end of their inpatient stay. There was a further increase from discharge to the 6-month follow-up for self-efficacy and quality of life. In respect to the functional severity of asthma, children of both groups showed a significant improvement. Whether these effects have long-term stability and which parents benefit from which type of intervention will be the objective of an ongoing 12-month follow-up.


A paler shade of green? The toxicology of biodiesel emissions: Recent findings from studies with this alternative fuel.
Biodiesel produced primarily from plants and algal feedstocks is believed to have advantages for production and use compared to petroleum and to some other fuel sources. There is some speculation that exposure to biodiesel combustion emissions may not induce biological responses or health effects or at a minimum reduce the effects relative to other fuels. In evaluating the overall environmental and health effects of biodiesel production to end use scenario, empirical data or modeling data based on such data are needed. This manuscript examines the available toxicology reports examining combustion derived biodiesel emissions since approximately 2007, when our last review of the topic occurred. Toxicity derived from other end uses of biodiesel - e.g., spills, dermal absorption, etc. - are not examined. Findings from biodiesel emissions are roughly divided into three areas: whole non-human animal model exposures; in vitro exposures of mammalian and bacterial cells (used for mutation studies primarily); and human exposures in controlled or other exposure fashions. Overall, these more current studies clearly demonstrate that biodiesel combustion emission exposure- to either 100% biodiesel or a blend in petroleum diesel- can induce biological effects. There are reports that show biodiesel exposure generally induces more effects or a greater magnitude of effect than petroleum diesel, however there are also a similar number of reports showing the opposite trend. It is unclear whether effects induced by exposure to a blend are greater than exposure to 100% biodiesel. Taken together, the evidence suggest biodiesel emissions can have some similar effects as diesel emissions on inflammatory, vascular, mutagenic, and other responses. While acute biodiesel exposures can show toxicity with a variety of endpoints, the potential effects on human health need further validation. Additionally there are few or no findings to date on whether biodiesel emissions can induce effects or even a weaker response that petroleum diesel with repeated exposure scenarios such as in an occupational setting. This article is part of a Special Issue entitled Air Pollution, edited by Wenjun Ding, Andrew J. Ghio and Weidong Wu.


Moderating factors for the effectiveness of group art therapy for schizophrenia: secondary analysis of data from the MATISSE randomised controlled trial.
Although some studies suggest that art therapy may be useful in the treatment of negative symptoms of schizophrenia, a recent large trial of group art therapy found no clinical advantage over standard care, but the study population was heterogeneous and uptake of the intervention was poor. This study aimed to investigate whether art therapy was more effective for specific subgroups of patients. Secondary analysis of data from a randomised controlled trial of group art therapy as an adjunctive treatment for schizophrenia (n = 140) versus standard care alone (n = 137). Positive and Negative Syndrome Scale scores at 12 months were compared between trial arms. Interaction between intervention effect and different subgroups, including those with more severe negative symptoms of schizophrenia, and those who expressed a preference for art therapy prior to randomisation, was tested using a linear mixed model. The clinical effectiveness of group art therapy did not significantly differ between participants with more or less severe negative symptoms [interaction for difference in PANSS = 1.7, 95 % CI (-8.6 to 12.1), P = 0.741], or between those who did and did not express a preference for art therapy [interaction = 3.9, 95 % CI (-6.7 to 14.5), P = 0.473]. None of the other exploratory subgroups suggested differences in intervention effect. There was no evidence of greater improvement in clinical symptoms of schizophrenia for those with more severe negative symptoms or those with a preference for art therapy. Identification of patients with schizophrenia who may benefit most from group art therapy remains elusive.


Polymeric diaquabis[mu4-1,3,5-benzenetricarboxylato(3-)](mu-4,4'-bipyridine)trizinc(II).
The solvothermal reaction of zinc(II) acetate with 1,3,5-benzenetricarboxylic acid and 4,4'-bipyridine in 1-butanol and acetic acid solution gives the title complex, [Zn(3)(C(9)H(3)O(6))(2)(C(10)H(8)N(2))(H(2)O)(2)](n). There are two different coordination environments for the Zn atom, namely ZnNO(2)(H(2)O) and ZnO(4); in the latter case, the Zn atom lies on a twofold symmetry axis. Carboxylate-bridged Zn(3)(O(2)C)(6) clusters are connected through 1,3,5-benzenetricarboxylate and 4,4'-bipyridine ligands (which lie about inversion centers), yielding a three-dimensional framework.


Complications of endodontically treated abutment teeth after restoration with non-precious metal double crowns.
This study aimed to evaluate the effects of endodontic treatment on the complication rate in abutment teeth following double crown treatment. Data of 233 patients supplied with 278 prostheses on 773 teeth were retrospectively analyzed. The 60-month cumulative complication rate for vital, root filled, and post and core reconstructed abutment teeth is calculated using the Kaplan-Meier method. Cox regression is performed to evaluate factors including age, sex, jaw, and tooth number. After 60 months, the cumulative complication rate for all abutment teeth was 24.1% (CI: 19.7-28.5%). A significantly higher cumulative fracture rate (log-rank test, p < 0.001) was found for devital (51.7%; CI: 35.3-68.1%) compared to vital abutment teeth (20.6%; CI: 16.2-25%). Devital teeth restored with post and core reconstructions (46.3%; CI: 26.1-66.5%) showed a lower cumulative fracture rate than abutment teeth with only root fillings (60.9%; CI: 33.5-88.3%). Abutment teeth in severely reduced dentitions (≤ 3 teeth) were found to have significantly lower survival rates than abutment teeth in not severely reduced dentitions (≥ 4 teeth, p = 0.031, HR = 0.609). Lower abutment teeth survival rates were associated with non-vitality and a reduced number of abutment teeth. Devital teeth with post and core reconstructions showed higher survival rates than root filled devital teeth. After 5 years, devital teeth with double crowns have a fracture rate twice as high as vital teeth. This prognosis should be taken into account during treatment planning, especially in the severely reduced dentition.


Pericardial patch augmentation for repair of incompetent bicuspid aortic valves at midterm.
Reoperation rates after repair of bicuspid aortic valves are higher than for mitral valve reconstruction. Satisfactory results have been reported for patch augmentation for tricuspid aortic valves. We have applied this technique for the repair of bicuspid aortic valves. Autologous pericardium is sutured to the free edge of the prolapsing bicuspid leaflet. A large coaptation surface is created and competence of the bicuspid valve is achieved. Forty patients underwent reconstruction of their bicuspid aortic valves by pericardial patch augmentation. Patients were followed up at regular intervals by echocardiography in yearly intervals. There were no perioperative deaths. One year postoperatively, one patient died due to endocarditis. Seven patients (17.5%) had aortic regurgitation grade I, and the other 33 patients had non or trivial aortic regurgitation at discharge. At 4.2+/-3.1 years postoperatively, only four patients (10%) had aortic regurgitation grade I. There were no cases of progression of regurgitation. Planimetric effective orifice areas ranged above 2 cm2. Mean aortic gradients dropped from 8.2+/-4.8 mmHg at discharge to 3.8+/-3 at four years and the mean height of coaptation surface from 14.7+/-2mm to 12.3+/-4, respectively. The pericardial patch augmentation technique increases coaptation surface, and thus provides reliable early and midterm competence of reconstructed bicuspid aortic valves.


A comprehensive review on food waste anaerobic digestion: Research updates and tendencies.
Anaerobic digestion has been practically applied in agricultural and industrial waste treatment and recognized as an economical-effective way for food waste disposal. This paper presented an overview on the researches about anaerobic digestion of food waste. Technologies (e.g., pretreatment, co-digestion, inhibition and mitigation, anaerobic digestion systems, etc.) were introduced and evaluated on the basis of bibliometric analysis. Results indicated that ethanol and aerobic prefermentation were novel approaches to enhance substrates hydrolysis and methane yield. With the promotion of resource recovery, more attention should be paid to biorefinery technologies which can produce more useful products toward zero emissions. Furthermore, a technological route for food waste conversion based on anaerobic digestion was proposed.


The comparative effect of ovarian hormone administration on bone mineral status in oophorectomized rats.
The effect of oophorectomy and hormone replacement therapy on cortical and trabecular bone mass was assessed in Sprague-Dawley rats. Bone mineral density (BMD) of the femur and the lumbar spine was determined by dual photon absorptiometry 4 months after surgery. Femoral mineral content was also determined. A significant decrease in bone density and in calcium content was observed after surgical castration. Bone mineral loss was prevented by either progesterone or estrogen, while the combination of progesterone and estrogen had no effect on the bone mineral content. The present study suggests the possibility that estrogen-progestin treatment may be less effective than a therapy with estrogen alone, and that further study on the effect of progesterone alone would be worthwhile.


Optical and electrochemical detection of DNA.
There is a growing demand for the production of a DNA biosensor with applications in medicine, the food industry, agriculture, veterinary science and environmental science. In this paper we describe methods for the optical and electrochemical detection of DNA using the enzyme horseradish peroxidase (EC 18.104.22.168) and glucose oxidase (EC 220.127.116.11). We have used bis-methylacridinium nitrate and luminol for the optical detection of DNA using a purpose built, inexpensive luminometer. Using this system detection limits of 10(-11) g of plasmid DNA have been observed. Electrochemical detection of DNA was carried out by the use of a fluoride ion selective electrode and stripping voltammetry. DNA was detected down to 10(-9)-10(-10) g of DNA by the enzymatic release of halogen ions from organohalogen compounds.


Toward the improvement of trail classification in national parks using the recreation opportunity spectrum approach.
Trail settings in national parks are essential management tools for improving both ecological conservation efforts and the quality of visitor experiences. This study proposes a plan for the appropriate maintenance of trails in Chubusangaku National Park, Japan, based on the recreation opportunity spectrum (ROS) approach. First, we distributed 452 questionnaires to determine park visitors' preferences for setting a trail (response rate = 68 %). Respondents' preferences were then evaluated according to the following seven parameters: access, remoteness, naturalness, facilities and site management, social encounters, visitor impact, and visitor management. Using nonmetric multidimensional scaling and cluster analysis, the visitors were classified into seven groups. Last, we classified the actual trails according to the visitor questionnaire criteria to examine the discrepancy between visitors' preferences and actual trail settings. The actual trail classification indicated that while most developed trails were located in accessible places, primitive trails were located in remote areas. However, interestingly, two visitor groups seemed to prefer a well-conserved natural environment and, simultaneously, easily accessible trails. This finding does not correspond to a premise of the ROS approach, which supposes that primitive trails should be located in remote areas without ready access. Based on this study's results, we propose that creating trails, which afford visitors the opportunity to experience a well-conserved natural environment in accessible areas is a useful means to provide visitors with diverse recreation opportunities. The process of data collection and analysis in this study can be one approach to produce ROS maps for providing visitors with recreational opportunities of greater diversity and higher quality.


Analytical performance and potential clinical utility of the GenMark Dx ePlex® blood culture identification gram-positive panel.
The test performance and potential clinical utility of the ePlex® BCID Gram-Positive (GP) Panel was evaluated relative to MALDI-TOF mass spectrometry on bacterial isolates and traditional antimicrobial susceptibility testing. All GP bacteria (n = 100) in the study were represented on the panel including 50 common skin contaminants, and 7/7 coinfections. The positive percent agreement (PPA) was 97/97 with 2 false positives. Detection of vanA yielded a PPA of 4/4 and NPA of 9/9. mecA gene detection exhibited a PPA of 14/14 and NPA of 14/14 for S. aureus and a PPA of 31/32(97%) and NPA of 16/16 for CNS with 1 false negative. Chart reviews (n = 80) identified a mean 24.4h faster time to organism identification, 53.4h earlier optimization in 15(18.8%) patients based on AMR gene detection, 29.2h earlier optimization for 8(10%) patients infected with organisms, such as streptococci, with very low resistance rates, and 42.9h earlier discontinuation of antimicrobials for 14(17.5%) patients with contaminant cultures.


Trends of Trauma Admissions in a Rural Trauma Center During Coronavirus Disease 2019 Pandemic.
The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to implementing strict social distancing mandates nationwide. This study evaluates the trauma trends during the pandemic at a rural level II trauma center in Pennsylvania. A retrospective review of all trauma registries between 2018 and 2021 was performed overall and on a 6-month basis. Injury severity score, injury types-blunt versus penetrating, and mechanisms of injury were compared across the years. A total of 3056 patients in 2018-2019 and 2506 patients in 2020-2021 were evaluated as the historic control and study group, respectively. The median age of the patients was 63 and 62 years in the control and the study group, respectively (P = 0.616). There was an overall significant decline in blunt injuries and an increase in penetrating injuries (Blunt: 2945 versus 2329, Penetrating: 89 versus 159, P < 0.001). Injury severity score was not different across the eras. Falls, motorcycle accidents, motor vehicle accidents, and all-terrain vehicles comprised most of the blunt traumas. Penetrating injuries secondary to assault with firearms and sharp weapons had an increasing trend. There was no association between trauma numbers and the beginning of the pandemic. Overall, there was a decline in trauma numbers during the second 6 mo of the pandemic. There was an increase in injuries involving firearms and stabbing. Rural trauma centers have a unique demographic and admission trend that should be considered while advising regulatory changes during pandemics.


Experimental anaplasmosis in mule deer: persistence of infection of Anaplasma marginale and susceptibility to A. ovis.
An experimental Anaplasma marginale infection was induced in a splenectomized mule deer (Odocoileus hemionus hemionus) which persisted subclinically at least 376 days as detected by subinoculation into susceptible cattle. Anaplasma ovis was experimentally transmitted from sheep to a splenectomized and a spleen-intact mule deer, and back to sheep. The pathogenesis in deer was very similar to that seen in sheep using ovine blood inoculations.


Pattern of combined collapse of right upper and right middle lobes.
Three cases of combined collapse of the right upper and middle lobes are presented. The appearance is the mirror image of collapse of the left upper lobe. The radiographic appearance is described, and possible causes and mechanisms of collapse are discussed.


Equity in access to zero-fees and low-cost Primary Health Care in Aotearoa New Zealand: Results from repeated waves of the New Zealand Health Survey, 1996-2016.
Primary Health Care in Aotearoa New Zealand is mainly funded through capitation-based funding to general practices, supplemented by a user co-payment. Funding is designed in part to keep the costs of care low for key groups in the population who have higher health needs. We investigated changes in the socio-demographic determinants of no-cost and low-cost access to Primary Health Care using data from sequential waves of the New Zealand Health Survey (1996/97-2016/17). Fees paid were self-reported and inflated using CPI-adjustment to the value of the 2018NZD. Over the 20-year study period, there was an increase in the population accessing low-cost care. Access to low-cost care was particularly high for Pacific people, but also higher for Māori and Asian people compared to Other/New Zealand European ethnicities. Area-level deprivation was a stronger predictor of access to low-cost care for non-Māori than for Māori. Although Māori were more likely than non-Māori to access low-cost care at all levels of deprivation, this was less evident in more deprived compared to more affluent areas. Given ongoing reported inequity for Māori being less able to afford primary health care, we suggest that future policies to improve access should be fully aligned with the articles of Te Tiriti o Waitangi and should focus on equity.


Displaced fat pads in trauma to the elbow.
A study was made of all the X-ray films of elbows taken in a casualty department in 1975, to determine the significance of posterior fat pad displacement. Posterior displacement was always found to indicate a fracture, whereas anterior displacement occasionally occurred without a fracture.


Direct evidence for inhibition of free radical formation from Cu(I) and hydrogen peroxide by glutathione and other potential ligands using the EPR spin-trapping technique.
Copper-induced oxidative damage is generally attributed to the formation of the highly reactive hydroxyl radical by a mechanism analogous to the Haber-Weiss cycle for Fe(II) and H2O2. In the present work, the reaction between the Cu(I) ion and H2O2 is studied using the EPR spin-trapping technique. The hydroxyl radical adduct was observed when Cu(I), dissolved in acetonitrile under N2, was added to pH 7.4 phosphate buffer containing 100 mM 5,5-dimethyl-1-pyrroline N-oxide (DMPO). Formation of the hydroxyl radical was dependent on the presence of O2 and subsequent formation of H2O2. The kscav/kDMPO ratios obtained were below those expected for a mechanism involving free hydroxyl radical and reflect the interference of nucleophilic addition of H2O to DMPO to form the DMPO/.OH adduct in the presence of nonchelated copper ion. Addition of ethanol or dimethyl sulfoxide to the reaction suggests that a high-valent metal intermediate, possibly Cu(III), was also formed. Spin trapping of hydroxyl radical was almost completely inhibited upon addition of Cu(I) to a solution of either nitrilotriacetate or histidine, even though the copper was fully oxidized to Cu(II) and H2O2 was formed. Bathocuproinedisulfonate, thiourea, and reduced glutathione all stabilized the Cu(I) ion toward oxidation by O2. Upon addition of H2O2, the Cu(I) in all three complexes was oxidized to varying degrees; however, only the thiourea complex was fully oxidized within 2 min of reaction and produced detectable hydroxyl radicals. No radicals were detected from the bathocuproinedisulfonate or glutathione complexes. Overall, these results suggest that the deleterious effects of copper ions in vivo are diminished by biochemical chelators, especially glutathione, which probably has a major role in moderating the toxicological effects of copper.


How does art making work? Testing the hypothesized mechanisms of art making on pain experience.
Pain is a multidimensional experience that requires a holistic pain management approach. Art making, a holistic, mind-body-spirit approach, has been used as a pain management strategy. Although findings of empirical studies point toward several potential mechanisms through which art making activity may affect the pain experience, these mechanisms have not yet been tested. Therefore, the purpose of this study is to evaluate whether perceived control, self-efficacy, spirituality, and mood mediate the effect of art making activity on pain. This study is a secondary analysis of cross-sectional survey data collected in 2014 for the Health and Retirement Study (HRS). Data from a national sample of 731 adults, 50 years of age or older were analyzed for the current study. Participants completed a health survey which included measures of art engagement (representing 'effect of art making' in this study), pain severity and interference, and proposed mediating variables (e.g., perceived control, self-efficacy, spirituality and mood). The joint significance test was used to test hypothesized mediation. We found that positive mood mediated the effects of art engagement on pain, but perceived control, self-efficacy, spirituality, and negative mood did not. Engagement in art making activity was associated with more positive mood (β = 0.213, p = .001). In turn, greater positive mood was associated with lower pain severity (β = -.147, p = .010) and pain interference (β = -.519, p = .034). Results of this study provide preliminary evidence that engagement in art making activity impacts pain experience by enhancing positive mood. A large prospective study examining the hypothesized mediating relationship is necessary to confirm our findings.


Clustering and colocalization in transmission immunoelectron microscopy: a brief review.
This mini-review tries to summarize the state of the art of stereological and statistical approaches used in clustering (in single immunogold labelling) and colocalization (in double immunogold labelling) studies of gold particles in transmission immunoelectron microscopy. The point pattern analysis may be useful to compare experimental pattern data to the null hypothesis of complete spatial randomness (CSR), and, furthermore to quantify the amount of clustering and/or colocalization. In particular, this paper gives an overview about the most recent literature on the subject and different approaches will be only briefly summarized.


From proliferation to target innervation: signaling molecules that direct sympathetic nervous system development.
The sympathetic division of the autonomic nervous system includes a variety of cells including neurons, endocrine cells and glial cells. A recent study (Furlan et al. 2017) has revised thinking about the developmental origin of these cells. It now appears that sympathetic neurons and chromaffin cells of the adrenal medulla do not have an immediate common ancestor in the form a "sympathoadrenal cell", as has been long believed. Instead, chromaffin cells arise from Schwann cell precursors. This review integrates the new findings with the expanding body of knowledge on the signalling pathways and transcription factors that regulate the origin of cells of the sympathetic division of the autonomic nervous system.


Evolution of regional left ventricular wall motion abnormalities in acute Q and non-Q wave myocardial infarction.
The evolution of segmental wall motion in Q and non-Q wave acute myocardial infarction was studied in detail in 15 patients without known prior ischemic events. Serial two-dimensional echocardiographic studies were performed beginning early after the onset of chest pain and continuing until 10 to 14 days after admission. An area of apparent infarction was identified on each initial study based on later correlation of ECG and echocardiographic findings. Wall motion of infarct-and noninfarct-related areas was graded in a semiquantitative fashion based on the scoring of a visual analysis. Sequential image data demonstrated significant spontaneous improvement in wall motion of the infarct area in non-Q but not in Q wave events. Patients with non-Q wave infarction and improvement in regional function were at high risk for recurrent infarction within 6 months. Improvement in wall motion inside or outside the area of infarction in Q wave events was related to future risk. We concluded that in patients with initial acute myocardial infarction, failure to develop Q waves correlated with return of function in the apparent area of infarction. Improvement in regional wall motion after the initial study suggested risk for future ischemic events in both ECG types of myocardial infarction. Serial echocardiographic imaging may be a means to identify patients at risk for infarct extension in both non-Q and Q wave events.


Quantitation of gastrin and somatostatin cell populations in the antral mucosa of the rat. Comparative distribution and evolution through different life stages.
Total antral gastrin and somatostatin cell populations as well as their relative distribution pattern throughout the antrum were studied in rats with advancing age from birth time to old age. Both endocrine cell populations were estimated, after staining by immunoperoxidase technique, with a quantitative method using serial parallel strips from entire stomachs. Gastrin cells were regularly found at less than 1 h of post-natal life, but were few in number (447 +/- 82) cells. Somatostatin cells, not seen at birth, were observed in all rats at seven post-natal days; then they increased in number less rapidly but more regularly than gastrin cells. During the normal adult period, corrected gastrin cell population corresponds to about 330,000-500,000 cells and corrected somatostatin cell populations to about 130,000-200,000 cells. For the whole antrum the ratio of gastrin cell to somatostatin cell populations decreases through the rat life from 6.5 at 7 days to 1.5 in old age with a stable value, 2.5, during adult period. Examination of the topographical distribution throughout the antrum of these two populations shows that, strip per strip, their numerical ratio varies. Homogeneous values for the latter occur in the middle part of antrum and, as rule, in each group they reflect the mean value calculated for the whole of the antrum.


Combined effects of high-fat feeding and circadian desynchronization.
To assess whether circadian desynchronization leads to metabolic alterations capable of promoting dietary obesity and/or impairing glucose tolerance. Rats fed either with chow pellets (i.e., low-fat diet with 4% mass of fat) or high-fat diet (34% mass of fat). Half of each diet group was exposed to a fixed light-dark cycle or to a 10-h weekly shift in the light-dark cycle from Thursday to Sunday (20 shifts). To enforce the shifted animals to be active at unusual times of the day, food was available only during the daily dark period for all groups. Shifting the light-dark cycle on a weekly basis was efficient to induce circadian desynchronization, as evidenced by strong disturbances in the daily expression of locomotor activity. Shifted rats fed with a nocturnal low-fat diet had lower plasma insulin and similar blood glucose compared to rats fed with the same diet under a fixed light-dark cycle. Nocturnal high-fat feeding led to an abdominal fat overload associated with increased plasma leptin and basal glucose. These metabolic changes were not significantly modified by circadian desynchronization. Chronic desynchronization with low-fat diet impaired insulin regulation. Metabolic changes induced by the high-fat diet were not aggravated by chronic desynchronization.


Optimization of an adverse outcome pathway network on chemical-induced cholestasis using an artificial intelligence-assisted data collection and confidence level quantification approach.
Adverse outcome pathway (AOP) networks are versatile tools in toxicology and risk assessment that capture and visualize mechanisms driving toxicity originating from various data sources. They share a common structure consisting of a set of molecular initiating events and key events, connected by key event relationships, leading to the actual adverse outcome. AOP networks are to be considered living documents that should be frequently updated by feeding in new data. Such iterative optimization exercises are typically done manually, which not only is a time-consuming effort, but also bears the risk of overlooking critical data. The present study introduces a novel approach for AOP network optimization of a previously published AOP network on chemical-induced cholestasis using artificial intelligence to facilitate automated data collection followed by subsequent quantitative confidence assessment of molecular initiating events, key events, and key event relationships. Artificial intelligence-assisted data collection was performed by means of the free web platform Sysrev. Confidence levels of the tailored Bradford-Hill criteria were quantified for the purpose of weight-of-evidence assessment of the optimized AOP network. Scores were calculated for biological plausibility, empirical evidence, and essentiality, and were integrated into a total key event relationship confidence value. The optimized AOP network was visualized using Cytoscape with the node size representing the incidence of the key event and the edge size indicating the total confidence in the key event relationship. This resulted in the identification of 38 and 135 unique key events and key event relationships, respectively. Transporter changes was the key event with the highest incidence, and formed the most confident key event relationship with the adverse outcome, cholestasis. Other important key events present in the AOP network include: nuclear receptor changes, intracellular bile acid accumulation, bile acid synthesis changes, oxidative stress, inflammation and apoptosis. This process led to the creation of an extensively informative AOP network focused on chemical-induced cholestasis. This optimized AOP network may serve as a mechanistic compass for the development of a battery of in vitro assays to reliably predict chemical-induced cholestatic injury.


Copper and zinc deficiencies treatement by intramuscular injections in sheep.
In two experiments, compared to 10 control, 10 ewes were injected intramuscularly either with metallic copper dust or zinc oxide, suspended in purified olive oil. Copper injection raised the plasma and hepatic copper of the treated ewes. Similarly, injected zinc oxide produced a rise in plasma zinc. These increases started respectively on the 6th and 3rd day after the injection and lasted till the 21st or 17th day. No detrimental inflammation appeared. This form of treatment is therefore efficient against trace element deficiencies without any side effect.


Comparative Evaluation of Effect of Micro-Osteoperforation and Mechanical Vibration on Rate of Orthodontic Tooth Movement in Young Adults With Bimaxillary Protrusion.
To evaluate and compare the rate of orthodontic tooth movement and root resorption by micro-osteoperforation (MOP) and mechanical vibration in young adults with bimaxillary protrusion. Twenty patients having class I bimaxillary protrusion who required all first premolar extraction were allocated into two groups MOP (Group A) and mechanical vibration (Group B), with a 1:1 allocation ratio. After leveling alignment MOP was performed on either side of the arch, and vibration was applied on the contralateral side 20 mins per day. Canines were retracted with nickel-titanium coil springs, and Alginate impressions were taken every four weeks till 4 months. The mean rate of retraction of canines of Group A was more than Group B. There was a statistically significant difference between Group A and Group B. (p=0.0120) Conclusion: The mean rate of retraction of canines treated by MOP was 1.15 mm per 4 weeks, and by mechanical vibration, 0.8mm per 4 weeks.