Prevalence and characteristics of impaired glucose metabolism in patients referred to comprehensive cardiac rehabilitation: the DANSUK study.
Lifestyle and pharmacological interventions can delay the progression of impaired glucose tolerance (IGT) to type 2 diabetes (T2DM), and there is growing evidence that earlier detection of T2DM and intensified risk factor management may result in improved cardiovascular morbidity and mortality. We studied the prevalence of impaired glucose metabolism (T2DM, IGT and impaired fasting glucose; IFG) in patients referred to cardiac rehabilitation, and further studied whether we could identify groups in which an oral glucose tolerance test (OGTT) need not be performed. As part of a cardiac rehabilitation trial, 201 patients participated. Patients without a diagnosis of T2DM (N=159) underwent an OGTT 3 months after inclusion. Forty-two patients (21%) had known T2DM at enrolment. Based on the OGTT, 26 patients (13%) had unrecognized T2DM, 36 (18%) had IGT and 19 (9%) were diagnosed with isolated IFG according to the World Health Organization definition. Using fasting plasma glucose alone, 19% of the patients with unrecognized T2DM and two-thirds of patients with IGT would be misclassified. Using IFG as a means to detect IGT showed a sensitivity of only 33% and a positive predictive value of 39%. More than 60% of the patients (123/201) referred to cardiac rehabilitation had impaired glucose metabolism and 18% of the screened patients (29/159) would be misclassified if an OGTT was omitted. IFG and IGT did not identify the same patients or the same cardiovascular risk profile. An OGTT test should therefore be considered a constituent part of routine care management in cardiac rehabilitation settings.


Electron beam irradiation of maltodextrin and cinnamyl alcohol mixtures: influence of glycerol on cross-linking.
The influence of glycerol on the electron beam-induced changes in maltodextrins-cinnamyl alcohol (CA) blends is examined with respect to its influence on the degree of chain scission, grafting, and cross-linking. The study is relevant to radiation-induced polysaccharide modification, specifically in the perspective of using blended starch as a thermoplastic material, where glycerol is commonly used as a plasticizer. In the absence of CA, glycerol protects maltodextrin from chromophore formation onto the main chain, but also induces more chain scission. The presence of CA provides efficient radiation-protection against scission. Glycerol is shown to affect the interaction between maltodextrin and CA, most likely in the form of an inclusion complex when glycerol is absent. The global behavior under radiation is therefore governed by the physical interactions between the blend constituents rather than on the role of glycerol role as a plasticizer, or as an OH˙ radical scavenger.


Prevalence of Skin Sensitization to Pollen of Date Palm in Marrakesh, Morocco.
Background. Date palm's pollen has been identified as a source of allergy; the rate of sensitization of this pollen is between 6 and 29%. Objective. To determine the prevalence of sensitization to date palm in Marrakesh and to identify the clinical profile. Patients and Methods. This study is based on a questionnaire and the prick test on 7 allergens, in population aged 5 years and above with clinical symptoms suggesting allergic diseases, from November 2012 to February 2013 in Marrakech. Results. We included 468 patients (women: 79.5%). The prick tests were considered interpretable in 467 cases. The prevalence of skin sensitization to pollen of date palm was 6.6%. The 31 cases of sensitization to date palm involved 7 men and 24 women with an average age of 37.5 years. Cutaneous monosensitization to date palm's pollen was observed in 2 cases. Asthma, rhinitis, and conjunctivitis were recorded, respectively, in 48.4%, 93.5%, and 67.7%. Conclusion. Skin sensitization to pollen of date palm does not seem unusual among allergic patients in Marrakech and is comparable to that found in Casablanca (7%), Barcelona (6.6%), and Cartagena (6.1%).


Potential of Aedes aegypti and Aedes albopictus populations in the Central African Republic to transmit enzootic chikungunya virus strains.
Major chikungunya outbreaks have affected several Central African countries during the past decade. The chikungunya virus (CHIKV) was isolated from humans and sylvan mosquitoes in the Central African Republic (CAR) during the 1970 and 1980s but has not been found recently, despite the presence of Aedes albopictus since 2010. The risk of a massive chikungunya epidemic is therefore potentially high, as the human populations are immunologically naïve and because of the presence of the mosquito vector. In order to estimate the risk of a large outbreak, we assessed the vector competence of local Ae. aegypti and Ae. albopictus populations for ancient local strains of CHIKV in CAR. Mosquitoes were orally infected with the virus, and its presence in mosquito saliva was analysed 7 and 14 days post-infection (dpi) by quantitative reverse transcriptase polymerase chain reaction. The two species had similar infection rates at 7 and 14 days, and the dissemination rate of both vectors was ≥ 80% at 14 dpi. Only females followed up to 14 dpi had CHKV in their saliva. These results confirm the risk of transmission of enzootic CHIKV by anthropophilic vectors such as Ae. aegypti and Ae. albopictus.


"How might a low-cost hospital system look?" Lessons from the Rochester experience.
An innovative, collaborative approach to promoting the effective and efficient delivery of hospital services and to maintaining the solvency of the nine participating hospitals in the greater Rochester, New York area has been successful. An evaluation of the early years (1980-1984) of the Hospital Experimental Payments Program (HEP) shows: 1) per capita hospital costs in Rochester increased at half the rate of increase of the national average; 2) by 1984, per capita hospital expenditures were at $446 compared with $521 nationally; 3) cost containment was achieved through a wide array of strategies such as changes in hospital resource allocation and physician practice patterns; and 4) during the same period, quality and access remained stable or improved. This project demonstrates that through self-control, hospitals can become efficient providers of health care.


Analysing mathematical modelling tasks in light of citizenship education using the COVID-19 pandemic as a case study.
In this paper, we discuss the theoretical background of mathematical modelling and its connection to citizenship education. Citizenship education in this context means that young people are equipped with competencies to respond as responsible citizens in situations relevant for society. To outline the connection between mathematical modelling and citizenship education in theory, we discuss the aims of mathematical modelling, modelling competences and the connection between numeracy and modelling. Based on these reflections we present an extended modelling cycle that specifically highlights modelling steps relevant to citizenship education. To show how the theoretical connection between mathematical modelling and citizenship education can be used in teaching practice, we describe three different examples of modelling tasks and analyse them with the help of the extended modelling cycle. We argue that the three tasks support different learning aims in relation to citizenship education and require modellers to carry out different steps of the extended modelling cycle. As an example of context, we used the pandemic caused by COVID-19, as it affected the quality of human life greatly, as all students in the Western world experienced.


Hypotheses concerning the aetiology of Alzheimer's disease.
Theories on the aetiology and pathogenesis of Alzheimer's disease (AD) are revised. After discussing senile involution, the principal characteristic alterations of AD are presented. These pathological changes include involutive morphological phenomena (neurofibrillar tangles, senile neuritic plaques with varying = amyloid content) and functional phenomena (alterations in energy metabolism, in protein synthesis, and in the neurotransmitter metabolism). Currently it is assumed that the neurons most affected seem to be primarily those of the ascending cholinergic activating system, whose somas are situated in Meinert's basal nucleus. Serotoninergic, adrenergic and peptidergic brainstem neurons and serotoninergic neurons of the cerebral cortex are also affected. Secondary to these, the main pathological alterations, triggered by these disfunctions, are observed in neurons of the neocortex, hippocampus and amygdala. These changes are responsible for the symptoms of AD. The aetiology of these changes may be genetic = (related to chromosoma 21), toxic (aluminium) or infective (slow agents similar to those that cause Creutzfeldt-Jakob disease, kuru and scrapie). Various aetiopathological theories emphasized on immunological or vascular phenomena, altered protein synthesis, etc. It seems to be important that certain neurons are affected in most of degenerative diseases: the high-risk neurons. These neurons could be affected by toxic and environmental factors.


Effects of FK506 on rat thymus: time-course analysis by immunoperoxidase technique and flow cytofluorometry.
The effect of administration of FK506 at 1 mg/kg body weight for 14 days on rat lymphoid tissues, especially the thymus, and recovery after discontinuation of treatment, were investigated by the immunoperoxidase technique and flow cytofluorometry using monoclonal antibodies OX6, OX7, OX8, OX18 and W3/25, reactive with rat lymphocytes. Marked reduction of the thymic medulla upon treatment was clearly demonstrated by staining with OX18 and OX6. Changes produced by FK506 were also observed in the cortical area of the thymus, and were especially marked in the subcapsular area and around blood vessels. Eventually, the thymic cortex appeared patchy, this change being maximal 14 days after the start of administration. Obvious restitution of the thymic medulla was evident about 14 days after withdrawal of FK506. Flow cytometric analysis of the thymus showed that the percentages of cells labelled positively with OX7, OX8 and W3/25 were increased with FK506 treatment, and recovered to the normal level soon after withdrawal. Furthermore, the peak of fluorescence intensity of OX7+, OX8+ and W3/25+ cells showed a temporary shift to the right during FK506 treatment; however, the peak of fluorescence intensity of OX18+ cells showed a temporary shift to the left. Treatment with FK506 also produced a significant change in 3H-thymidine uptake by thymocyte. These results suggest that FK506 may inhibit the proliferation, maturation and differentiation of thymocytes. However, thymocytes prepared from FK506-treated rats and labelled with FITC behaved similarly to rat thymocytes in normal recipient rats. This suggests that during FK506 treatment thymocytes may retain their potential for peripheral mobilization.


[Classification of renal failure].
The authors analyze the data available in the literature on acute and chronic renal failure (ARF and CRF, respectively). The mechanisms of their development (common and distinctive) are pathogenetically assessed and the functional reserve of the kidneys is determined. The phasic character of development of renal failure (compensation, subcompensation and decompensation) is pathogenetically substantiated. ARF and CRF are shown to be two forms of renal failure development which have both pathogenetic and distinctive characteristics in its mechanisms.


Vignettes as a novel research tool in spiritual care: A methods paper.
To discuss the construction and use of vignettes as a novel approach in spiritual care research and education. Methods paper. In this methods paper, the authors introduce the use of vignettes in spiritual care research and provide insight into the construction of vignettes. The vignette presented was part of a study of neurosurgical nurses' attitudes and responses to the spiritual needs of neuro-oncology patients. The development process, consisting of four steps, is explained in this paper. Using a vignette to explore nurses' attitudes towards spiritual care is an innovative way to understand what behaviours nurses consider appropriate in situations where the patient is seeking meaning and connection. Transparent description of the development process is crucial to ensure reproducibility. The use of theoretically constructed and validated vignettes in spiritual care research is new. Vignettes used in surveys have the potential to elicit nurses' responses to patients' search for meaning and connectedness. In order to investigate nurses' attitudes and behaviours towards patients' spiritual needs, carefully constructed and validated vignettes are valuable research tools. Vignettes have proven to be a valuable research tool in the social and health sciences. So far, their use as a survey instrument in spiritual care research has not been investigated. Therefore, this method paper introduces vignettes as a novel approach to spiritual care research. Our findings contribute to the further development of vignettes in nursing science, as there are similarities with case development and simulation training in nursing education. Reporting guideline is not applicable. No patient or public contribution.


Cervical Cancer Markers: Epigenetics and microRNAs.
Gynecologic malignant neoplasms are a severe health problem among female patients, of which cervical cancer (CC), in particular, is a common disease leading to high mortality rates. Despite extensive attempts by researchers to solve the molecular mystery of CC, the mechanisms of its pathogenesis remain unclear. Tumor markers used in the clinical laboratory, such as squamous cell carcinoma (SCC), cancer antigen (CA)-125, and CA19-9, provide some help in diagnosing patients with CC. However, finding new molecular markers with high sensitivity and specificity is necessary. This review focuses on the role of epigenetic changes, particularly microRNAs (miRNAs), to CC. Several miRNAs that associated with CC potentially have the advantage of being early biomarkers. Moreover, altered serum miRNAs or single nucleotide polymorphisms in miRNA patterns may predict disease progression.


Ribitol dehydrogenase messenger RNA from an enzyme superproducer strain of Klebsiella aerogenes. Purification, cell-free translation and studies in vitro and in vivo.
1. Ribitol dehydrogenase messenger RNA, from a strain of Klebsiella aerogenes that had been evolved to superproduce this enzyme, has been purified in a single step by labelling extracted polysomes with rabbit anti(ribitol dehydrogenase) and immunoprecipitating with sheep anti-(rabbit IgG). 2. The extracted mRNA is stable in a protein synthesis system in vitro and directs synthesis 35-40-times more efficiently than RNA from coliphages MS2 or Q beta, to give ribitol dehydrogenase as sole major product. 3. Its size distribution shows a major band of 1500 nucleotides plus fragments 400-1400 nucleotides, with only traces of size 2400-3000 nucleotides. Only the latter could encode both proteins of the operon: ribitol dehydrogenase and D-ribulokinase. 4. Ribitol dehydrogenase mRNA represents 24% of total mRNA in cells harvested just after a 'switch' point' in mid-exponential phase. About half of the polysomes containing this mRNA are unattached to DNA, whereas only 3% of other mRNAs are unattached to DNA. 5. This mRNA is not outstandingly stable in vivo, though there are indications that it may be more stable than average. Hence the high level of synthesis of ribitol dehydrogenase (up to 30% of total protein in an extract) seems to be due to very efficient transcription and translation from multiple copies of a constitutive rbtD gene.


Alveolar bone preservation subsequent to miniscrew implant placement in a canine model.
To assess the effects of transcortical screws on alveolar (bone) ridge preservation following extraction. Four adult beagle dogs had mandibular premolars extracted bilaterally. After 6 weeks, using a split-mouth design, two transcortical screws were inserted unilaterally below the alveolar crest on the experimental side in the region of the extraction. The dogs were killed after 12 weeks. The bone at the extraction sites was analyzed using μCT and 3D analysis. A cylindrical core was placed around the actual and a virtual screw placed in the identical location on the control side. The bone volume within the cylinders was quantified. An insertion of a dental implant was simulated bilaterally at the insertion site. The height of the clinical crown and the alveolar crest were determined on both sides. The bone turnover was assessed histomorphometrically on un-decalcified bucco-lingual sections stained with basic fuchsine and toluidine blue. Comparison of the two sides revealed a significant difference both with regard to the bone volume and morphology. The transcortical screw caused an increase in bone density and less ridge atrophy. When simulating a dental implant placement on both sides, the bone preservation on the experimental side led to a need for a shorter clinical crown compared to the control side. A higher activity level of the bone in the experimental side was demonstrated histologically. In this dog model the insertion of a mini-implant across the healing alveolar process results in increased density not only adjacent to the screws, but also in the region where a potential dental implant would be inserted. In humans, the insertion of transcortical screws may maintain bone when for various reasons insertion of a permanent dental implant has to be postponed.


Progesterone via its receptor antagonizes the pro-inflammatory activity of estrogen in the mouse uterus.
Populations of macrophages and neutrophils in the uterus are under the control of the female sex steroids estrogen and progesterone (P4). Their influx is induced by estrogen, while P4 can both stimulate and inhibit leukocyte influx depending on the timing of P4 with respect to estrogen. Regulation of leukocytes has been implicated in changes in uterine immune responses during the estrous cycle, pregnancy, and implantation. This work demonstrates that P4 given concurrently with estrogen to ovariectomized mice for 4 days antagonizes the ability of estrogen to recruit macrophages and neutrophils into the mouse uterus. Using progesterone receptor knockout (PRKO) mice, we show that this effect is dependent on progesterone receptors (PR). In the absence of PR, neutrophils recruited by estrogen were found to be degranulated, partially explaining the edema that is observed with long-term treatment of PRKO mice with estrogen and P4. Populations of B lymphocyte cells were shown to be unchanged by estrogen and P4 treatment in both wild-type and PRKO mice. The neutrophil chemotactic chemokine MIP-2 was examined for down-regulation by P4 but was found to be unaffected by hormonal treatment. Together, these observations demonstrate that PR has a strong anti-inflammatory role in the mouse uterus when estrogen and P4 are present together.


Legionella pneumophila induces IFNbeta in lung epithelial cells via IPS-1 and IRF3, which also control bacterial replication.
Legionella pneumophila, a Gram-negative facultative intracellular bacterium, causes severe pneumonia (Legionnaires' disease). Type I interferons (IFNs) were so far associated with antiviral immunity, but recent studies also indicated a role of these cytokines in immune responses against (intracellular) bacteria. Here we show that wild-type L. pneumophila and flagellin-deficient Legionella, but not L. pneumophila lacking a functional type IV secretion system Dot/Icm, or heat-inactivated Legionella induced IFNbeta expression in human lung epithelial cells. We found that factor (IRF)-3 and NF-kappaB-p65 translocated into the nucleus and bound to the IFNbeta gene enhancer after L. pneumophila infection of lung epithelial cells. RNA interference demonstrated that in addition to IRF3, the caspase recruitment domain (CARD)-containing adapter molecule IPS-1 (interferon-beta promoter stimulator 1) is crucial for L. pneumophila-induced IFNbeta expression, whereas other CARD-possessing molecules, such as RIG-I (retinoic acid-inducible protein I), MDA5 (melanoma differentiation-associated gene 5), Nod27 (nucleotide-binding oligomerization domain protein 27), and ASC (apoptosis-associated speck-like protein containing a CARD) seemed not to be involved. Finally, bacterial multiplication assays in small interfering RNA-treated cells indicated that IPS-1, IRF3, and IFNbeta were essential for the control of intracellular replication of L. pneumophila in lung epithelial cells. In conclusion, we demonstrated a critical role of IPS-1, IRF3, and IFNbeta in Legionella infection of lung epithelium.


[Dynamics of CO2, CH4 and N2O emission fluxes from mires during freezing and thawing season].
In the Sanjiang Plain, the freezing and thawing phase have 7 - 8 months and play important role in the greenhouse gases emission. The characters of the greenhouse gases emission during freezing and thawing season in the Sanjiang Plain were studied, using the static chamber and gas chromatogram method. The results observed show that there were obvious CH4 and CO2 emissions in winter and the CH4 emission made a relatively large contribution to the total CH4 flux from the different type mires during the winter in the Sanjiang Plain. And there were significantly CH4 and CO2 emission peak values during thawing time. The CH4 and CO2 emissions fluxes from seasonal flooded mire were larger than that from continuously flooded mire during thawing time. On the contrary, the CH4 and CO2 emissions from continuously flooded mire were larger than that from seasonal flooded mire in winter. During thawing, there was exponential relationship between CO2 fluxes and the soil temperature (5cm) (R2 = 0.912, p< 0.001). Meanwhile, CO2 fluxes was obviously correlated with the CH4 emission fluxes (R2 = 0.751, p < 0.001). The mires are N2O sink in winter and gradually become N2O source, with increasing temperature during thawing time. The characters of the greenhouse gases emission, during freezing and thawing in the Sanjiang Plain respond to the microbial activity in winter and the effects of thawing on soil carbon mineralization, nitrification and denitrification.


The yeast nuclear gene CBS1 is required for translation of mitochondrial mRNAs bearing the cob 5' untranslated leader.
Mitochondrial translation of the cob mRNA to yield apocytochrome b is specifically dependent on the nuclear gene CBS1, while mitochondrial translation of the oxi2 mRNA to yield cytochrome oxidase subunit III (cox III) is specifically dependent on the nuclear gene PET494. Chimeric oxi2 mRNAs bearing the 5' leaders of other mitochondrial mRNAs, transcribed from rho- mitochondrial DNAs termed MSU494, are translated in pet494 mutants. In this study, we examined translation of coxIII from MSU494-encoded chimeric mRNAs in zygotes of defined nuclear and mitochondrial genotype. CoxIII was translated from a chimeric mRNA bearing the cob leader only when the zygotes contained a wild-type CBS1 gene. CoxIII translation from an mRNA bearing the 5' leader of the mitochondrial gene aap1 was not dependent on CBS1 activity. We conclude that the product of the nuclear gene CBS1, or something under its control, acts in the mitochondrion on the cob mRNA 5' leader to activate translation of down-stream coding sequences.


New deltochiline (Coleoptera: Scarabaeidae: Scarabaeinae) taxa associated with hyrax dung in arid south western Namibia.
A survey of rock hyrax dung middens along the arid escarpment of southwest Namibia has filled a gap in the range shown by members of the Byrrhidium group of flightless dung beetles (Coleoptera: Scarabaeidae: Scarabaeinae) belonging to the tribe Deltochilini. The survey discovered a new genus and species, Ausmontins jacobsi new genus and species, and a further four new species in two previously described genera, Namakwanus kamfferi new species, Namakwanus minutus new species, Namaphilus nubibmontanus new species and Namaphilus tirasmontanus new species. They are described and illustrated in the present paper. This addition of new taxa raises the total complement of the Byrrhidium group to seven genera and 19 species. An updated key to all the known species is also provided. It is probable that further taxa await discovery.


[Optic nerve neuropathy in the course of giant cell arteritis].
Anterior ischemic optic neuropathy (AION) is the result of infarct of the optic nerve head, caused by occlusion of one or more short posterior ciliary arteries. On the base of different treatment and prognosis there are two forms of AION: arteritic and non-arteritic (NAION). Arteritic ischemic optic neuropathy is caused by giant cell arteritis (GCA). The most typical symptoms are: the sudden and deep vision loss and headache, scalp tenderness, jaw claudication, muscle ache, fever and weight loss. The ophthalmologist usually finds an abnormal pupil, a swollen optic nerve (disc edema), and peripheral or central vision loss (or both). About 70% of cases are not progressive, i.e., the vision remains stable, but reduced. The ESR is usually markedly elevated. Temporal artery biopsy is useful in confirming the diagnosis of arteritic AION. Treatment involves the immediate administration of systemic steroids. Though steroid therapy rarely results in the return of vision, it is beneficial in protecting the fellow eye from vision loss and improving long-term systemic health.


Switching of the core structures of glycosphingolipids from globo- and lacto- to ganglio-series upon human embryonic stem cell differentiation.
A systematic survey of expression profiles of glycosphingolipids (GSLs) in two hESC lines and their differentiated embryoid body (EB) outgrowth with three germ layers was carried out using immunofluorescence, flow cytometry, and MALDI-MS and MS/MS analyses. In addition to the well-known hESC-specific markers stage-specific embryonic antigen 3 (SSEA-3) and SSEA-4, we identified several globosides and lacto-series GSLs, previously unrevealed in hESCs, including Gb(4)Cer, Lc(4)Cer, fucosyl Lc(4)Cer, Globo H, and disialyl Gb(5)Cer. During hESC differentiation into EBs, MS analysis revealed a clear-cut switch in the core structures of GSLs from globo- and lacto- to ganglio-series, which was not as evident by immunostaining with antibodies against SSEA-3 and SSEA-4, owing to their cross-reactivities with various glycosphingolipids. Such a switch was attributable to altered expression of key glycosyltransferases (GTs) in the biosynthetic pathways by the up-regulation of ganglio-series-related GTs with simultaneous down-regulation of globo- and lacto-series-related GTs. Thus, these results provide insights into the unique stage-specific transition and mechanism for alterations of GSL core structures during hESC differentiation. In addition, unique glycan structures uncovered by MS analyses may serve as surface markers for further delineation of hESCs and help identify of their functional roles not only in hESCs but also in cancers.


Ethics -- perceived or reasoned from principles?: a rejoinder to Korn, Huelsman, and Reed.
In response to Korn, Huelsman, and Reed's (1992) question, "Who defines those interests, and how serious must the setback be?" (p. 126), we argue that a wrongful (unjust) harm (a setback of interest) is not equivalent to a hurt (a temporary distressing mental state) and that the interests of importance are welfare interests (general means to our ulterior aims), not just a desire to avoid unpleasant mental states (hurts). To set back a welfare interest is to reverse its course or to impede, thwart, defeat, or doom it. It is the primary responsibility of the investigator to define both welfare interests and the risk of harm. An informed consent -- one with substantial understanding, in substantial absence of control by others, and given intentionally -- allows participants to autonomously authorize participation in research, including their toleration of acts of mental discomfort or distress during an experiment. Not only were our participants not wrongfully harmed, they benefited and were willing to volunteer for future research. No strong evidence has been advanced or linked to guided imagery in a way that would justify its restraint; to so claim evokes a standard of legal paternalism that fails to respect participants' competence and autonomy to choose to participate in research on rape using guided imagery.


A new Co(II) complex of diniconazole: synthesis, crystal structure and antifungal activity.
A new Co(II) complex of diniconazole, namely diaqua[(E)-(RS)-1-(2,4-dichlorophenyl)-4,4-dimethyl-2-(1H-1,2,4-triazol-1-yl-κN(4))pent-1-en-3-ol]cobalt(II) dinitrate dihydrate, [Co(C15H17Cl2N3O)3(H2O)2](NO3)2·2H2O, was synthesized and characterized by elemental analysis, IR spectroscopy and single-crystal X-ray diffraction. Crystal structural analysis shows that the centrosymmetric Co(II) cation is coordinated by four diniconazole ligands and two water molecules, forming a six-coordinated octahedral structure. There are also two free nitrate counter-anions and two additional solvent water molecules in the structure. Intermolecular O-H...O hydrogen bonds link the complex cations into a one-dimensional chain. In addition, the antifungal activity of the complex against Botryosphaeria ribis, Gibberella nicotiancola, Botryosphaeria berengriana and Alternariasolani was studied. The results indicate that the complex shows a higher antifungal activity for Botryosphaeria ribis and Botryosphaeria berengriana than diniconazole, but a lower antifungal activity for Gibberella nicotiancola and Alternariasolani.


The Relational Materiality of Groundwater.
This paper is part of a larger research project which draws out ways of knowing and thinking with groundwater from Chennai, south India. The (under)ground or (sub)terranean environment is a thick and complex, three-dimensional space of "nothing but change," but whose utility is essential to sustaining urban life above it. This paper looks at multiple, specific, and contradictory ways in which the materiality of groundwater is understood and intervened in. Using the case of the ongoing Chennai Metro Rail construction project, and its disciplinary cultures of representation, I bring attention to the ground and its waters as a composite system in both balance and unrest, and an active, vital component of the city. Through unpacking established concepts of strata, porosity, and pressure, I will cast groundwater not as an objective fact, always pictured by, and relative to, a human subject, but as an actual being which humans (and others beyond) perceive, relate to, and come into contact with. I close by drawing from this account a possible further set of concepts which groundwater generates-dynamic states which are common to human and material life-suggesting that a relational theory of groundwater materiality, based on leaking as opposed to bordering, might better respond to the ways in which groundwater troubles knowledge.


Hypertension induced by pregnancy and neonatal outcome: Results from a retrospective cohort study in preterm under 34 weeks.
The present study seeks to assess the impact of gestational hypertensive disorders on premature newborns below 34 weeks and to establish the main morbidities and mortality in the neonatal period and at 18 months. A retrospective observational study was carried out with 695 premature newborns of gestational age (GA) between 24 and 33 weeks and 6 days, born alive in the Neonatal ICU of Brasília's Mother and Child Hospital (HMIB), in the period from January 1, 2014, to July 31, 2019. In total, 308 infants were born to hypertensive mothers (G1) and 387 to normotensive mothers (G2). Twin pregnancies and diabetic patients with severe malformations were excluded. Outcomes during hospitalization and outcomes of interest were evaluated: respiratory distress syndrome (RDS), brain ultrasonography, diagnosis of bronchopulmonary dysplasia (BPD), diagnosis of necrotizing enterocolitis, retinopathy of prematurity, breastfeeding rate at discharge, survival at discharge and at 18 months of chronological age and relationship between weight and gestational age. Newborns with hypertensive mothers had significantly lower measurements of birth weight and head circumference. The G1 group had a higher risk small for gestational age (OR 2.4; CI 95% 1.6-3.6; p <0.00), as well as a greater risk of being born with a weight less than 850 g (OR 2.4; 95% CI 1.2-3.5; p <0.00). Newborns of mothers with hypertension presented more necrotizing enterocolitis (OR 2.0; CI 95% 1.1-3.7); however, resuscitation in the delivery room and the need to use surfactant did not differ between groups, nor did the length of stay on mechanical ventilation, or dependence on oxygen at 36 weeks of gestational age. Survival was better in newborns of normotensive mothers, and this was a protective factor against death (OR 0.7; 95% CI 0.5-0.9; p <0.01). In the follow-up clinic, survival at 18 months of chronological age was similar between groups, with rates of 95.3% and 92.1% among hypertensive and normotensive mothers, respectively. Exclusive breastfeeding at discharge was 73.4% in the group of hypertensive women and 77.3% in the group of normotensive mothers. There were no significant differences between groups. Among the analyzed outcomes, arterial hypertension during pregnancy can increase the risk of low weight, small babies for gestational age (SGA), deaths in the neonatal period and enterocolitis, with no differences in weight and survival at 18 months of chronological age. Arterial hypertension presents a high risk of prematurity in the neonatal period, with no difference at 18 months of age.


The use of data from sampling for bacteriology for genetic selection against clinical mastitis.
One breeding objective of Dutch cattle breeders is to improve genetic resistance against clinical and subclinical mastitis. Because of a lack of direct mastitis information, udder health breeding values are based on indirect traits. Inclusion of direct information on clinical mastitis could improve reliability of breeding values. The aim of this study was to investigate whether data from milk samples sent in for bacteriology are potential sources of information for the occurrence of mastitis, which may be used in animal breeding, and if so how this data can be used. Although there are 2 separate flows of milk samples for bacteriology in the Netherlands, it was not considered necessary to account for the origin of the samples. In both flows, the majority of the samples are visually normal and flow-specific traits are highly correlated. Therefore, information from these flows is combined for genetic analysis. Nearly two-thirds of the bacteriology data could be linked to milk recording and pedigree records. Relatively few farmers (<3%) took 5 or more samples for bacteriology between January 1, 2003, and March 31, 2006. Their herds had, on average, greater milk production and lower cell counts than herds for which no samples were taken. However, the range and variation within both groups of herds for these variables was similar and there was a large overlap in sires used within both groups. Whether or not samples were taken for bacteriology turned out to be a potentially useful indicator for clinical mastitis at the cow level, because this trait had a strong positive genetic correlation with clinical mastitis registered by farmers (0.84 or 0.89, depending on the data set) and similar heritability (2%) and genetic variation. Also, genetic correlations of bacteriology with SCC traits were similar to those for farmer-registered clinical mastitis. An important advantage of these bacteriology data is that they are already collected routinely and stored in a central database in the Netherlands; this is not the case for registration of clinical cases. Thus, data from bacteriological culturing can be used for genetic improvement of udder health.


Reassignment of human renin gene to chromosome 1q32 in studies of a (1;4)(q42;p16) translocation.
The human renin gene (REN) has been assigned to chromosome 1q42. Linkage studies are, however, inconsistent with this localization. We therefore reexamined the question of the location of REN using a patient whose distal chromosome 1q arm was translocated to chromosome 4 [(1;4)(q42;p16)]. In situ hybridization using a 3H-labelled REN probe demonstrated hybridization signals confined to the q32 band of chromosome 1, with radioactivity in the translocated 1q42 region being similar to the low levels along all other chromosomes.


Lymphocyte subpopulations analysis in peripheral blood in polymyalgia rheumatica/giant cell arteritis.
The phenotypic characteristics of peripheral blood lymphocytes were investigated in 22 patients suffering from active polymyalgia rheumatica/giant cell arteritis (PMR/GCA) prior to steroid treatment. We observed a significant reduction in the absolute number and the relative percentage of CD4-, CD8+ and CD3+, CD16+ and/or CD56+ cells compared to controls. Fifteen patients were investigated prospectively over a 6-month period of prednisone therapy. At the end of the study CD4-CD8+ cells had increased significantly compared to baselines, CD3+ CD16+ and/or CD56+ cells remained significantly lower when compared to controls. We did not observe any abnormalities in the absolute number and percentage of HLA-DR+ T lymphocytes, CD5+ B cells and NK cell phenotypes before or during steroid treatment. Our study confirms that there was significant increase in the absolute number of CD8+ T cells during steroid treatment in the PMR/GCA patients, but indicates the persistence of an immunological alteration despite the control of disease manifestations.


Evaluation of the Use of a Virtual Patient on Student Competence and Confidence in Performing Simulated Clinic Visits.
Objective. To assess the effect of incorporating virtual patient activities in a pharmacy skills lab on student competence and confidence when conducting real-time comprehensive clinic visits with mock patients. Methods. Students were randomly assigned to a control or intervention group. The control group completed the clinic visit prior to completing virtual patient activities. The intervention group completed the virtual patient activities prior to the clinic visit. Student proficiency was evaluated in the mock lab. All students completed additional exercises with the virtual patient and were subsequently assessed. Student impressions were assessed via a pre- and post-experience survey. Results. Student performance conducting clinic visits was higher in the intervention group compared to the control group. Overall student performance continued to improve in the subsequent module. There was no change in student confidence from pre- to post-experience. Student rating of the ease of use and realistic simulation of the virtual patient increased; however, student rating of the helpfulness of the virtual patient decreased. Despite student rating of the helpfulness of the virtual patient program, student performance improved. Conclusion. Virtual patient activities enhanced student performance during mock clinic visits. Students felt the virtual patient realistically simulated a real patient. Virtual patients may provide additional learning opportunities for students.


Ionic liquid solutions as extractive solvents for value-added compounds from biomass.
In the past few years, the number of studies regarding the application of ionic liquids (ILs) as alternative solvents to extract value-added compounds from biomass has been growing. Based on an extended compilation and analysis of the data hitherto reported, the main objective of this review is to provide an overview on the use of ILs and their mixtures with molecular solvents for the extraction of value-added compounds present in natural sources. The ILs (or IL solutions) investigated as solvents for the extraction of natural compounds, such as alkaloids, flavonoids, terpenoids, lipids, among others, are outlined. The extraction techniques employed, namely solid-liquid extraction, and microwave-assisted and ultrasound-assisted extractions, are emphasized and discussed in terms of extraction yields and purification factors. Furthermore, the evaluation of the IL chemical structure and the optimization of the process conditions (IL concentration, temperature, biomass-solvent ratio, etc.) are critically addressed. Major conclusions on the role of the ILs towards the extraction mechanisms and improved extraction yields are additionally provided. The isolation and recovery procedures of the value-added compounds are ascertained as well as some scattered strategies already reported for the IL solvent recovery and reusability. Finally, a critical analysis on the economic impact versus the extraction performance of IL-based methodologies was also carried out and is here presented and discussed.


Intraoperative Tumor Perforation is Associated with Decreased 5-Year Survival in Colon Cancer: A Nationwide Database Study.
It is a widely held belief that intraoperative tumor perforation in colon cancer impairs survival and causes local recurrence, although the prognostic importance remains unclear. The aim of this study was to assess the effect of unintended intraoperative tumor perforation on postoperative mortality and long-term survival. This national cohort study was based on data from a prospectively maintained nationwide colorectal cancer database. We included 16,517 colon cancer patients who were resected with curative intent from 2001 to 2012. Intraoperative tumor perforation produced a significantly impaired 5-year survival of 40% compared to 64% in non-perforated colon cancer. Intraoperative tumor perforation was an independent risk factor for death, hazard ratio 1.63 (95% confidence interval: 1.4-1.94), with a significantly increased 90-day postoperative mortality of 17% compared to 7% in non-perforated tumors, p < 0.001. We showed that tumor fixation, emergency operations, and laparotomies were associated with an increased risk of intraoperative tumor perforation. This nationwide study demonstrates that intraoperative tumor perforation in colon cancer is associated with statistically significant reduced long-term survival and increased postoperative mortality.


Interaction between ADH1C Arg(272)Gln and alcohol intake in relation to breast cancer risk suggests that ethanol is the causal factor in alcohol related breast cancer.
Alcohol is a risk factor for breast cancer. We wanted to determine if ADH polymorphisms which modify the rate of ethanol oxidation to acetaldehyde, were associated with breast cancer risk. We matched 809 postmenopausal breast cancer cases with 809 controls, nested within the prospective Diet, Cancer and Health study. Among variant allele carriers of ADH1C Arg(272)Gln, alcohol intake increased the risk of breast cancer with 14% (95% CI: 1.04-1.24) per 10g alcohol/day, but not among homozygous wild type carriers (p for interaction=0.06). Thus, slow oxidation of ethanol seemed to be associated with breast cancer risk.


T-cell function is critical for murine cholesterol gallstone formation.
The formation of cholesterol gallstones is a complex process involving contributions from genes and environmental factors. Although gallbladder inflammation is believed to be common during cholelithogenesis, the role of immunologic factors is unknown. The role of adaptive immunity in cholesterol cholelithogenesis was analyzed utilizing immunocompetent Helicobacter spp.-infected and -uninfected BALB/c and congenic immunodeficient Rag2(-/-) (Rag) mice. Lymphocyte transfer studies were performed to determine which cellular subset was responsible for cholesterol gallstone formation. Also, gallbladder inflammation was quantified to determine the nature of the inflammatory response associated with cholelilithogenesis. When fed a lithogenic diet for 8 weeks, wild-type mice developed significantly more cholesterol gallstones (27%-80% prevalence) than Rag mice ( approximately 5%, P < .05). Helicobacter spp.-infected BALB/cJ mice displayed statistically significant increases in cholesterol gallstone prevalence compared with uninfected mice (81% vs. 39%; P < .05). Transfer of splenocytes or T lymphocytes to Rag2(-/-) mice increased stone prevalence markedly (26% and 40% respectively; P < .05), whereas transfer of B cells was not appreciably cholelithogenic (13%). The adaptive immune response increased the expression of gallbladder Muc genes and accumulation of mucin gel. In addition, T cells and cholesterol monohydrate crystals induced proinflammatory gene expression in the gallbladder, which likely contributes to gallbladder dysfunction. These studies indicate that T cells are critical in murine cholesterol cholelithogenesis. Furthermore, cholesterol monohydrate crystals induce expression of proinflammatory cytokines in a T-cell-dependent fashion. Acquired immunity and inflammation are likely to be crucial factors in cholesterol gallstone pathogenesis, rather then merely the result of cholelithogenesis.


The mouse mammary gland as a sentinel organ: distinguishing 'control' populations with diverse environmental histories.
There are numerous examples of laboratory animals that were inadvertently exposed to endocrine disrupting chemicals (EDCs) during the process of conducting experiments. Controlling contaminations in the laboratory is challenging, especially when their source is unknown. Unfortunately, EDC contaminations can interfere with the interpretation of data during toxicological evaluations. We propose that the male CD-1 mouse mammary gland is a sensitive bioassay to evaluate the inadvertent contamination of animal colonies. We evaluated mammary glands collected from two CD-1 mouse populations with distinct environmental histories. Population 1 was born and raised in a commercial laboratory with unknown EDC exposures; Population 2 was the second generation raised in an animal facility with limited exposures to xenoestrogens from caging, feed, etc. Mammary glands were collected from all animals and evaluated using morphometric techniques to quantify morphological characteristics of the mammary gland. Population 1 (with suspected history of environmental chemical exposure) and Population 2 (with known limited history of xenoestrogen exposure) were morphologically distinguishable in adult males, prepubertal females, and pubertal females. Mammary glands from males raised in the commercial animal facility were significantly more developed, with larger ductal trees and more branching points. The appearance of these mammary glands was consistent with prior reports of male mice exposed to low doses of bisphenol A (BPA) during early development. In females, the two populations were morphologically distinct at both prepuberty and puberty, with the most striking differences observed in the number, size, and density of terminal end buds, e.g. highly proliferative structures found in the developing mammary gland. Collectively, these results suggest that the mouse mammary gland has the potential to be used as a sentinel organ to evaluate and distinguish animal colonies raised in different environmental conditions including potential EDC exposures. Our findings could help researchers that wish to perform a posteriori evaluations to determine whether inadvertent contamination with xenoestrogens (and potentially other EDCs) has occurred in their animal colonies, especially after new materials (feed, caging, water bottles) have been introduced. Finally, our results challenge the relatively common practice of using historical controls in toxicological experiments.


The microarchitecture of C. elegans behavior during lethargus: homeostatic bout dynamics, a typical body posture, and regulation by a central neuron.
The nematode C. elegans develops through four larval stages before it reaches adulthood. At the transition between stages and before it sheds its cuticle, it exhibits a sleep-like behavior during a stage termed lethargus. The objectives of this study were to characterize in detail behavioral patterns and physiological activity of a command interneuron during lethargus. We found that lethargus behavior was composed of bouts of quiescence and motion. The duration of individual bouts ranged from 2 to 100 seconds, and their dynamics exhibited local homeostasis: the duration of bouts of quiescence positively correlated with the duration of bouts of motion that immediately preceded them in a cAMP-dependent manner. In addition, we identified a characteristic body posture during lethargus: the average curvature along the body of L4 lethargus larvae was lower than that of L4 larvae prior to lethargus, and the positions of body bends were distributed non-uniformly along the bodies of quiescent animals. Finally, we found that the AVA interneurons, a pair of backward command neurons, mediated locomotion patterns during L4 lethargus in similar fashion to their function in L4 larvae prior to lethargus. Interestingly, in both developmental stages backward locomotion was initiated and terminated asymmetrically with respect to AVA intraneuronal calcium concentration. The complex behavioral patterns during lethargus can be dissected to quantifiable elements, which exhibit rich temporal dynamics and are actively regulated by the nervous system. Our findings support the identification of lethargus as a sleep-like state. Iwanir S; Tramm N; Nagy S; Wright C; Ish D; Biron D. The microarchitecture of C. elegans behavior during lethargus: homeostatic bout dynamics, a typical body posture, and regulation by a central neuron. SLEEP 2013;36(3):385-395.


Pharmacokinetics of tipifarnib after oral and intravenous administration in subjects with advanced cancer.
The primary objective of this study was to identify intravenous regimens of tipifarnib that would mimic the systemic exposure obtained after the current twice-daily oral administration of tipifarnib. After determination of an intravenous dose that 6 subjects with advanced cancer could tolerate, another 26 subjects were randomly assigned to receive 3 consecutive 4-day regimens of tipifarnib with different treatment sequences: a 100-mg 2-hour intravenous infusion, 200-mg oral administration twice daily, and a 200-mg/d continuous intravenous infusion. The systemic exposure to tipifarnib was comparable among these 3 regimens. The plasma concentration-time profile of 2-hour intravenous infusion more closely resembled the oral administration than did the continuous infusion. Glucuronidation is a metabolic pathway for tipifarnib with concentrations of the glucuronide conjugate greatly exceeding the parent compound after oral and intravenous administration. Analysis of plasma metabolites indicated that tipifarnib also undergoes dealkylation and loss of the imidazole group.


Comparing human and mouse salivary glands: A practice guide for salivary researchers.
Mice are a widely utilized in vivo model for translational salivary gland research but must be used with caution. Specifically, mouse salivary glands are similar in many ways to human salivary glands (i.e., in terms of their anatomy, histology, and physiology) and are both readily available and relatively easy and affordable to maintain. However, there are some significant differences between the two organisms, and by extension, the salivary glands derived from them must be taken into account for translational studies. The current review details pertinent similarities and differences between human and mouse salivary glands and offers practical guidelines for using both for research purposes.


Vector control with driving Y chromosomes: modelling the evolution of resistance.
The introduction of new malaria control interventions has often led to the evolution of resistance, both of the parasite to new drugs and of the mosquito vector to new insecticides, compromising the efficacy of the interventions. Recent progress in molecular and population biology raises the possibility of new genetic-based interventions, and the potential for resistance to evolve against these should be considered. Here, population modelling is used to determine the main factors affecting the likelihood that resistance will evolve against a synthetic, nuclease-based driving Y chromosome that produces a male-biased sex ratio. A combination of deterministic differential equation models and stochastic analyses involving branching processes and Gillespie simulations is utilized to assess the probability that resistance evolves against a driving Y that otherwise is strong enough to eliminate the target population. The model considers resistance due to changes at the target site such that they are no longer cleaved by the nuclease, and due to trans-acting autosomal suppressor alleles. The probability that resistance evolves increases with the mutation rate and the intrinsic rate of increase of the population, and decreases with the strength of drive and any pleiotropic fitness costs of the resistant allele. In seasonally varying environments, the time of release can also affect the probability of resistance evolving. Trans-acting suppressor alleles are more likely to suffer stochastic loss at low frequencies than target site resistant alleles. As with any other intervention, there is a risk that resistance will evolve to new genetic approaches to vector control, and steps should be taken to minimize this probability. Two design features that should help in this regard are to reduce the rate at which resistant mutations arise, and to target sequences such that if they do arise, they impose a significant fitness cost on the mosquito.


The diagnosis of primary cardiac lymphoma was facilitated by computed tomographic coronary angiography.
Primary cardiac lymphoma (PCL) is a rare entity that leads to fatal symptoms such as serious arrhythmia. The present case was an 80-year-old female with severe dyspnea caused by 30 bpm bradycardia. Computed tomography revealed a tumor invading to the right inferior myocardium. A computed tomographic coronary angiography (CTCA) study revealed the right coronary artery penetrating the tumor with no invasion by the surrounding tumor. Because a percutaneous biopsy was unsuccessful, video-assisted thoracic surgery (VATS) was performed. The final pathological diagnosis was diffuse large B cell lymphoma. Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) chemotherapy reduced the size of the tumor, and the symptoms thereafter improved. An observation of the coronary artery penetrating the tumor without tumor invasion may be a characteristic finding of PCL. CTCA is useful to detect this finding. When a percutaneous biopsy is unavailable, VATS should be considered as a minimally invasive procedure to obtain a reliable diagnosis of PCL.


Phenotypic variability in a Spanish family with MNGIE.
Clinical, biochemical, and genetic features of a Spanish family with mitochondrial neurogastrointestinal encephalomyopathy are reported. The proband presented with severe gastrointestinal dysmotility and the affected sister had extraocular muscle weakness. In both affected individuals, biochemical defects of thymidine phosphorylase and a pathogenic G-to-A transition mutation at nucleotide 435 in the thymidine phosphorylase gene were identified. The first thymidine phosphorylase mutation identified in Spain showed phenotypic variability at onset.


Nostalgia and alligator bite--morbidity and mortality among Indian migrants to Natal, 1884-1911.
Reported causes of death (1899-1911) and of admission to hospital (1884-1910) of Indian migrants to Natal are analysed, and an attempt is made to relate them to the circumstances and way of life of the community. The most frequently reported causes of death were pneumonia, enteritis and pulmonary tuberculosis; the commonest reason for admission was venereal disease. Fluctuations in reported mortality and morbidity from year to year were most marked for malaria, with a formidable epidemic in 1905-1906. Typhoid fever and diphtheria were uncommon, as were diabetes and the sequelae of arteriosclerosis.


Acute- and late-phase matrix metalloproteinase (MMP)-9 activity is comparable in female and male rats after peripheral nerve injury.
In the peripheral nerve, pro-inflammatory matrix metalloproteinase (MMP)-9 performs essential functions in the acute response to injury. Whether MMP-9 activity contributes to late-phase injury or whether MMP-9 expression or activity after nerve injury is sexually dimorphic remains unknown. Patterns of MMP-9 expression, activity and excretion were assessed in a model of painful peripheral neuropathy, sciatic nerve chronic constriction injury (CCI), in female and male rats. Real-time Taqman RT-PCR for MMP-9 and its endogenous inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1) of nerve samples over a 2-month time course of CCI was followed by gelatin zymography of crude nerve extracts and purified MMP-9 from the extracts using gelatin Sepharose-beads. MMP excretion was determined using protease activity assay of urine in female and male rats with CCI. The initial upsurge in nerve MMP-9 expression at day 1 post-CCI was superseded more than 100-fold at day 28 post-CCI. The high level of MMP-9 expression in late-phase nerve injury was accompanied by the reduction in TIMP-1 level. The absence of MMP-9 in the normal nerve and the presence of multiple MMP-9 species (the proenzyme, mature enzyme, homodimers, and heterodimers) was observed at day 1 and day 28 post-CCI. The MMP-9 proenzyme and mature enzyme species dominated in the early- and late-phase nerve injury, consistent with the high and low level of TIMP-1 expression, respectively. The elevated nerve MMP-9 levels corresponded to the elevated urinary MMP excretion post-CCI. All of these findings were comparable in female and male rodents. The present study offers the first evidence for the excessive, uninhibited proteolytic MMP-9 activity during late-phase painful peripheral neuropathy and suggests that the pattern of MMP-9 expression, activity, and excretion after peripheral nerve injury is universal in both sexes.


Construction of epithelioid sheets by transfection of mouse sarcoma cells with cDNAs for chicken cell adhesion molecules.
Pleiomorphic mouse sarcoma S180 cells were transfected with cDNAs for the liver cell adhesion molecule (L-CAM), the neural cell adhesion molecule (N-CAM), or both CAMs. Transfected cells expressed the appropriate CAMs at their surface and those expressing L-CAM (S180L cells) changed from adjoining spindle or round shapes to a closely linked "epithelioid" sheet when grown to confluence. Cells transfected with cDNA for N-CAM (S180N cells) also expressed this CAM on the cell surfaces and bound brain vesicles containing N-CAM but showed no phenotypic change to an epithelioid state. In S180L cells and doubly transfected (S180L/N) cells, L-CAM was concentrated at regions of cell contact and was codistributed with cortical actin. In S180N cells, N-CAM was uniformly distributed on the cell surface. When S180L cells were cocultured with S180L/N cells, N-CAM was not concentrated at boundaries between the S180L and S180L/N cells but was concentrated at boundaries between pairs of S180L/N cells. Fab' fragments of anti-L-CAM dissociated the epithelioid sheets of S180L or S180L/N cells into cells with shapes resembling those of untransfected cells. Cells in epithelioid sheets were polygonal in shape but, unlike cells in true epithelia, had no basement membrane or polar structure; they also lacked tight junctions and desmosomes. Ultrastructural examination showed that, in contrast to the untransfected phenotype, cells in epithelioid sheets had large increases in adherens junctions and gap junctions. Dye coupling experiments indicated that the gap junctions were functional. The frequency of expression of both kinds of junctions was sharply decreased by treatment with anti-L-CAM Fab' fragments. These experiments provide support for the precedence hypothesis, which proposes that the linkage of cells by means of CAMs is a necessary event for the extensive expression of junctional structures.


Presession mood induction in therapists: Effects on therapist empathy.
Previous studies show that therapist mood is associated with psychotherapy processes, but the observational nature of these studies does not allow for causal inference. It is also unclear if other therapist characteristics, such as therapist trait empathy, moderate the relation between therapist mood and process variables. Thirty-four therapists and volunteer client dyads participated in three weekly counseling sessions. Before each session, therapists were induced to experience one of three moods, elation, depression, or neutral, in a counterbalanced order, using a combination of music and the Velten method. After each session, clients rated therapist empathy and session quality, therapists rated session quality, and observers rated therapist empathy using videotapes. Electrocardiogram was collected from therapists and clients during the session to assess heart rate synchrony as an indicator of therapist empathy. Therapist trait empathy moderated the effect of mood induction on observer-rated therapist empathy, such that when induced to experience elation, therapists with high trait empathy were observed to be more empathic, whereas therapists with low trait empathy were observed to be less empathic. Therapists of different trait empathy levels did not differ on observer-rated empathy when induced to experience depression or neutral mood. No significant effect of mood induction was found for client-rated empathy, client- and therapist-rated session quality, or heart rate synchrony. The experimental design offers preliminary evidence that therapist presession mood may influence the psychotherapy process. The findings are explained in light of empathy amplification and empathy attenuation hypotheses in relation to positive emotion. Practice and research implications are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


"RéaNet", the Internet utilization among surrogates of critically ill patients with sepsis.
Health-related Internet utilization is common but its use by proxies of critically ill patients is unknown. Our objective was to describe the prevalence and the Internet utilization characteristics among surrogates of critically ill septic patients. We conducted a prospective observational study in French ICUs. Three survey instruments were used to describe ICU organization regarding information delivery, patients and surrogates characteristics. 169 surrogates of 146 septic patients hospitalized in 19 ICUs were included. One sixth of ICUs (n = 3, 16%) had their own website. Majority of patients were males (n = 100, 68%), aged 64±1 years old, with a SAPS2 score at 53±17 and required vasopressors (n = 117, 83%), mechanical ventilation (n = 116, 82%). More than one quarter required renal replacement therapy (n = 36, 26%). Majority of surrogates were female, in their fifties. Only one in five knew the word sepsis (n = 27, 16%). Majority of proxies internet users (n = 77; 55%) search on the internet about sepsis. The main motivation was curiosity. Majority of surrogates found the information online reliable, suitable for request and concordant. Prior use of health-related Internet (OR = 20.7 [4.30-100.1]), the presence of a nursing staff during family-physician meetings (OR = 3.33 [1.17-9.53]), a younger patient age (OR = 1.32 [1.01-1.72]) and renal replacement therapy requirement (OR = 2.58 [1.06-6.26]) were associated with health-related Internet use. Neither satisfaction with medical care or information provision, neither presence of anxiety-depression symptoms, were associated with health-related Internet use. Majority of surrogates (N = 76 (52%)) would have like receiving a list of selected websites on sepsis. Majority of proxies of critically ill patients with sepsis use Internet to learn more about sepsis. Internet utilization is independent of satisfaction with global ICU care, perceived quality of information delivery by doctors or the existence of anxiety-depression symptoms during ICU stay. The delivery of a list of recommended web sites on sepsis would have been appreciated.


Synthetic lethality and cancer: cohesin and PARP at the replication fork.
Cohesins are mutated in a significant number of tumors of various types making them attractive targets for chemotherapeutic intervention. However, cohesins have a spectrum of cellular roles including sister chromatid cohesion, transcription, replication, and repair. Which of these roles are central to cancer biology and which roles can be exploited for therapeutic intervention? Genetic interaction networks in yeast have identified synthetic lethal interactions between mutations in cohesin and replication fork mediators. These interactions are conserved in worms and in human cells suggesting that inhibition of replication fork stability mediators such as poly (ADP-ribose) polymerase (PARP) could result in the specific killing of tumors with cohesin mutations. These findings also highlight the utility of genetic interaction networks in model organisms for the identification of clinically relevant interactions. Here, we review this type of approach, emphasizing the power of synthetic lethal interactions to reveal new avenues for developing cancer therapeutics.


The mechanism of rapamycin in the intervention of paraquat-induced acute lung injury in rats.
1. Paraquat (PQ) is an organic nitrogen heterocyclic herbicide that is widely used in agriculture throughout the world. Numerous studies have reported PQ intoxication on humans. 2. In this study, we established a rat lung injury model induced by PQ and evaluated the intervention effect of rapamycin on the model, exploring the pathogenesis of PQ on lung injury as well as therapeutic effects of rapamycin on PQ-induced lung injury. 3. A rat lung injury model was established by gavage of PQ, and rapamycin was used to treat the model animals with PQ-induced lung injury. Different physiological indices were measured through Western blot and real-time polymerase chain reaction to evaluate the effect of rapamycin on the PQ-induced lung injury. 4. The analyses showed that application of rapamycin could significantly reduce the lung injury damage caused by PQ, with lung tissue wet-dry weight ratio, pathological features, compositions in serum, protein in bronchoalveolar lavage fluid and other indices being significantly improved after the injection of rapamycin. 5. It was inferred that the use of rapamycin could improve the PQ-induced lung injury through inhibiting the activity of mTOR. And we expected the use of rapamycin to be a potential treatment method for the PQ intoxication in future.


Does treatment with beta-adrenoceptor antagonists in vivo alter human adenylate cyclase responsiveness in vitro?
1. Treatment with beta-adrenoceptor antagonists in vivo can alter adenylate cyclase responsiveness in the human heart. We have determined the effects of treatment with four different beta-adrenoceptor antagonists in vivo on the responsiveness of lymphocyte and platelet adenylate cyclase in vitro in healthy volunteers. 2. Propranolol (non-selective, 4 x 40 mg day), bisoprolol (beta 1-selective, 1 x 10 mg day), and ICI 118.551 (beta 2-selective, 3 x 25 mg day) were tested as drugs without and pindolol (non-selective, 2 x 5 mg day) as a drug with intrinsic sympathomimetic activity. Adenylate cyclase stimulation by GTP, prostaglandin E1 and forskolin was determined before, after a 7 day treatment period and 7 days after drug withdrawal. 3. Neither treatment with or withdrawal of any of the beta-adrenoceptor antagonists altered adenylate cyclase responsiveness. 4. We conclude that adenylate cyclase responsiveness in circulating blood cells underlies different regulatory mechanisms than that in solid tissues such as the human heart. Our data suggest that circulating blood cells do not always reflect alterations in solid tissues.


Reconciling Adaptation and Fidelity: Implications for Scaling Up High Quality Youth Programs.
In the field of prevention science, some consider fidelity to manualized protocols to be a hallmark of successful implementation. A growing number of scholars agree that high-quality implementation should also include some adaptations to local context, particularly as prevention programs are scaled up, in order to strengthen their relevance and increase participant engagement. From this perspective, fidelity and adaptation can both be seen as necessary, albeit mutually exclusive, dimensions of implementation quality. In this article, we propose that the relationship between these two constructs may be more complex, particularly when adaptations are consistent with the key principles underlying the program model. Our argument draws on examples from the implementation of a manualized youth voice program (YVP) in two different organizations serving six distinct communities. Through a series of retreats, implementers identified examples of modifications made and grouped them into themes. Results suggest that some adaptations were actually indicators of fidelity to the key principles of YVPs: power-sharing, youth ownership, and engagement in social change. We therefore offer suggestions for re-conceptualizing the fidelity-adaptation debate, highlight implications for measurement and assessment, and illustrate that the de facto treatment of adaptation and fidelity as opposing constructs may limit the diffusion or scaling up of these types of youth programs.


A population pharmacokinetic approach to describe cephalexin disposition in adult and aged dogs.
This study was conducted in order to characterize the pharmacokinetics of orally administered cephalexin to healthy adult and aged dogs, using a population pharmacokinetic approach. Two hundred and eighty-six cephalexin plasma concentrations obtained from previous pharmacokinetic studies were used. Sex, age, pharmaceutical formulation, and breed were evaluated as covariates. A one-compartment model with an absorption lag-time (Tlag) best described the data. The final model included age (adult; aged) on apparent volume of distribution (Vd/F), apparent elimination rate (ke/F), and Tlag; sex (female; male) on ke/F, and breed (Beagle; mixed-breed) on Vd/F. Addition of the covariates to the model explained 78% of the interindividal variability (IIV) in Vd/F, 36% in ke/F, and 24% in Tlag, respectively. Formulation did not affect the variability of any of the pharmacokinetic parameters. Tlag was longer, whereas Vd/F and ke/F were lower in aged compared to adult animals; in female aged dogs ke/F was lower than in male aged dogs; however, the differences were of low magnitude. Different disposition of cephalexin may be expected in aged dogs.


Predictors of cardiovascular events and associated mortality within two years of kidney transplantation.
Cardiovascular disease is the most common cause of death after renal transplantation. Furthermore, acute coronary syndrome (ACS) attributable to coronary artery disease (CAD) accounts for the majority of deaths due to cardiovascular disease posttransplant. While renal transplantation is the treatment of choice for end-stage renal disease, understanding the causes of graft and patient loss is exceedingly important to improve outcomes. This observational case-controlled study included 780 patients who underwent a kidney transplant between 1989 and 2001 who experienced early ACS (within 2 years). Patients were compared with controls matched for gender, year of transplant, and age. The primary outcome was the occurrence of an ACS event within 2 years after renal transplantation. Cardiovascular disease was the most common cause of death, with all 13 cardiovascular deaths due to CAD. An additional 15 episodes of nonfatal ACS episodes occurred. Thirty-seven percent of early ACS occurred perioperatively, the majority in the first 3 posttransplant months. On multivariate analysis, diabetes (OR [odds ratio] 5.56; P = .0007), smoking (OR 3.56; P = .034), and prior transplant (OR 2.81; P = .047) were associated with early ACS. Diabetes, smoking, and prior transplant were significantly associated with early ACS. The majority of events occurred perioperatively or within 3 months of transplant, highlighting the importance of improved screening and perioperative management.


4-Chlorophenylguanidine is an ASIC3 agonist and positive allosteric modulator.
Acid-sensing ion channels (ASICs) are proton-sensitive sodium channels that open in response to lowered extracellular pH and are expressed in the central and peripheral nervous systems. The ASIC3 subtype is found primarily in the periphery where the channel mediates pain signals caused by ischemia and inflammation. Here, we provide identify 4-chlorophenylguanidine (4-CPG) as an ASIC3 positive allosteric modulator and newest member of the growing group of guanidine modulators of ASICs. Furthermore, the 4-CPG reversed the effects of ASIC3 desensitization. The molecule 4-CPG offers a novel chemical backbone for the design of new ASIC3 ligands to study ASIC3 in vivo.


Mobilization of reserve proteins and activities of cysteine peptidases during germinative and post-germinative events of cowpea seeds.
Cysteine peptidases are the best characterized peptidases among those involved with storage protein mobilization during seed germination. In the present work we show two major groups of cysteine peptidase activities, one of higher (55 to 97 kDa) and other with lower (15 to 20 kDa) molecular masses which are temporally activated after 24 and 48 HAI, respectively, in germinating cowpeas. The former group is found both in protein bodies and in cytoplasmic fraction, while the latter is mostly present outside protein bodies. A third cysteine peptidase activity of ~37 kDa was specifically active at quiescent cotyledons and at 12 and 60 hours after imbibition (HAI). Main peptidase activities of albumin fractions were synchronizedly detected with radicle emergence at 36 HAI. Major vicilin mobilization was more pronounced from 60 HAI onwards and steadily increased until 144 HAI, when low levels of the smallest vicilin subunit were present. Cysteine peptidases were susceptible to iodoacetamide, E-64, iodoacetic acid, pCMB and β-mercaptoethanol, except for the ~37 kDa peptidase, which was not affected by any of the inhibitors. By a two-dimensional native/SDS-PAGE combination it was observed an apparent linear arrangement of protein breakdown products as well as of peptidase activity spots. The finding may indicate a complex set of sequential proteolytic events where peptidases induce or activate new peptidases, which may act upon different aggregates or zymogens, and these hydrolysis products appear in a line of constant decreasing Rf x Mr ratio.


Enhancement in vivo of the antiinflammatory and antitumor activities of type I interferon by association with the synthetic immunomodulator murabutide.
The therapeutic efficacy of type I interferon (IFN) has been reported to vary considerably in different indications. The use of the cytokine as adjuvant therapy has been suggested to enhance its efficacy and reduce the toxicity frequently associated with long-term and high-dose administration. In this study, we have assessed the activity of type I IFN in the protection against and treatment of acute hepatitis induced in mice by the administration of concanavalin-A (ConA). At the same time, we have evaluated the efficacy of the synthetic immunomodulator murabutide when administered alone or in combination with type I IFN to protect against ConA hepatitis and in the treatment of tumors in MethA sarcoma-bearing mice. Our results demonstrate a prophylactic effect as well therapeutic effects of type I IFN and of murabutide in the inflammation-mediated model of liver damage. The use of combination therapy presented enhanced efficacy in inhibiting the ConA-induced elevation of plasma transaminases. Both compounds were found to suppress IFN-gamma mRNA accumulation in the livers of ConA treated mice. This activity is discussed with respect to the mechanism of action of the two immunomodulators. In addition, the combination of murabutide with type I IFN exhibited synergistic antitumor activity that was clearly seen in the significant regression of MethA tumors and resulted in almost 50 percent tumor-free mice. The potential clinical application of combination therapies using a cytokine and a safe immunomodulator is analyzed in terms of enhancing the cytokine efficacy and extending its use to new indications.


Overdose Deaths Involving Fentanyl and Fentanyl Analogs - New York City, 2000-2017.
Unintentional drug overdose deaths have climbed to record high levels, claiming approximately 70,000 lives in the United States in 2017 alone (1). The emergence of illicitly manufactured fentanyl* (a synthetic, short-acting opioid with 50-100 times the potency of morphine) mixed into heroin, cocaine, and counterfeit pills, with or without the users' knowledge, has increased the risk for fatal overdose (2,3). The New York City (NYC) Department of Health and Mental Hygiene (DOHMH) conducts routine overdose mortality surveillance by linking death certificates with toxicology findings from the NYC Office of the Chief Medical Examiner (OCME). A 55% increase in the rate of fatal drug overdose in NYC was observed from 2015 to 2017, resulting in the highest number of overdose deaths recorded since systematic reporting began in 2000. Toxicology data indicate that this unprecedented increase in overdose deaths is attributable to fentanyl. Early identification of increased fentanyl involvement enabled DOHMH to respond rapidly to the opioid overdose epidemic by increasing awareness of the risks associated with fentanyl and developing effective risk reduction messaging. These results strongly suggest that, wherever possible, jurisdictions should consider integrating toxicology findings into routine overdose surveillance and work with local medical examiners or coroners to include fentanyl in the literal text on death certificates.


Surgery for dural ossification in association with cervical ossification of the posterior longitudinal ligament via an anterior approach.
Direct removal of an ossified mass via an anterior approach carries good decompression, to one- or two-level ossification of the posterior longitudinal ligament (OPLL) of the cervical spine. Ossification occasionally involves not only the posterior longitudinal ligament (PLL) but also the underlying dura mater. Defect of the dura mater by resection of the dural ossification (DO) can cause cerebrospinal fluid leakage or neural injury. The technique of resection of OPLL with floating of DO provides satisfactory decompression and avoids dural defect or neural injury in OPLL associated with DO. Four patients developed cervical myelopathy. Radiological examination revealed cord compression due to OPLL associated with DO. All patients underwent anterior procedures. After the necessary discectomies and corpectomies, OPLL was resected using a high-speed drill with a 4-mm steel burr and then with a 4-mm diamond burr. When the OPLL became paper-thin, it was separated from the dura mater using a microdissector and a Kerrison rongeur. There was a thin layer of the nonossified degenerated PLL between the residual OPLL and DO. Meticulous dissection of the residual OPLL over the DO was performed without removing the DO at this layer. Fixation was performed with a titanium cylindrical cage. This technical note describes the successful decompression of the spinal cord by removing OPLL only, and avoidance of dural defect or neural injury in cases of OPLL associated with DO.


Rectal cancer with synchronous liver metastases: Do we have a clear direction?
Rectal cancer is a common entity and often presents with synchronous liver metastases. There are discrepancies in management guidelines throughout the world regarding the treatment of advanced rectal cancer, which are further compounded when it presents with synchronous liver metastases. The following article examines the evidence regarding treatment options for patients with synchronous rectal liver metastases and suggests potential treatment algorithms.


Comparative study of oral lipid nanoparticle formulations (LNFs) for chemical stabilization of antitubercular drugs: physicochemical and cellular evaluation.
Rifampicin (RIF) and Isoniazid (INH) are two major first-line antitubercular drugs (ATDs) that are typically administered orally, in combination. However, INH-catalysed degradation of RIF under acidic pH environment of the stomach is a major concern related to its oral delivery, and is dramatically accelerated upon further exposure to and interaction with INH. This interaction, in turn, triggers a direct decline in the available RIF dose below the sub-therapeutic level, thereby diminishing its therapeutic efficacy. We hypothesized that encapsulation of both these important ATDs into lipid nanoparticle formulations (LNFs) may help mitigate the acid hydrolysis of RIF, its subsequent interaction with INH and its eventual INH-mediated accelerated chemical degradation in the gastric environment. We further hypothesized that these LNFs would be capable of enhanced uptake and localization into intra-cellular compartments of lung macrophages, thereby potentially targeting the Tb pathogen in its in vivo niche. For this purpose, we evaluated two promising LNFs, viz., solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) for encapsulating these ATDs. Here, we report on the design, development and comparative evaluation of SLN and NLC-based lipid formulations of both INH and RIF. Our strategy of nanoencapsulation substantially prolonged encapsulated RIF release and improved its chemical stability in presence of INH in a simulated gastric acidic environment. In vitro cell culture studies showed a well-quantifiable uptake of LNFs in a human alveolar macrophage cell line. Overall, these evaluations provided promising results for establishing the potential of both formulations for TB therapy.


Determining the binding site and binding affinity of estradiol to human serum albumin and holo-transferrin: fluorescence spectroscopic, isothermal titration calorimetry and molecular modeling approaches.
The interactions between estradiol and two carrier proteins, i.e. human serum albumin (HSA) and holo-transferrin (HTF) in aqueous solution at pH = 7.4 were studied by three-dimensional fluorescence emission spectroscopy, isothermal titration calorimetry (ITC), zeta-potential, resonance light-scattering and molecular modeling. Extensive fluorescence quenching was observed throughout the interaction between the drug and both proteins. Moreover, conformational changes were determined by observing the rearrangement of Trp residues during binding of estradiol with HSA and HTF at different concentrations. ITC experiments revealed that, in the presence of estradiol, both van der Waals forces and hydrogen bonding became predominant. In addition, other binding parameters such as enthalpy and entropy changes were determined by the zeta potential method. Molecular modeling suggested that estradiol was situated within sub-domain IB sited in the hydrophobic cluster in Site I, whereas the drug was located in the N-terminal of HTF where it was hydrogen bonded with Ala 670.


Stimulation of signal transduction pathways in osteoblasts by mechanical strain potentiated by parathyroid hormone.
Second-messenger systems have been implicated to transmit mechanical stimulation into cellular signals; however, there is no information on how mechanical stimulation is affected by such systemic factors as parathyroid hormone (PTH). Regulation of adenylyl cyclase and phosphatidylinositol pathways in rat dentoalveolar bone cells by mechanical strain and PTH was investigated. Two different cell populations were isolated after sequential enzyme digestions from dentoalveolar bone (group I and group II) to study potential differences in response. Mechanical strain was applied with 20 kPa of vacuum intermittently at 0.05 Hz for periods of 0.5, 1, 5, 10, and 30 minutes and 1, 3, and 7 days using the Flexercell system. Levels of cAMP, measured by RIA, and levels of inositol 1,4,5-triphosphate (IP3) and protein kinase C activity (PKC), measured by assay systems, increased with mechanical strain. When PTH was added to the cells, there was a significant increase in levels of all the intracellular signals, which appeared to potentiate the response to mechanical strain. IP3 levels (0.5 minute) peaked before those of PKC activity (5 minutes), which in turn peaked before those of cAMP (10 minutes). Group II cells showed higher levels of cAMP and IP3 than the group I cells. This suggests that the former may ultimately play the predominant roles in skeletal remodeling in response to strain. Immunolocalization of the cytoskeleton proteins vimentin and alpha-actinin, focal contact protein vinculin, and PKC showed a marked difference between strained and nonstrained cells. However, the addition of PTH did not cause any significant effect in cytoskeleton reorganization. Staining of PKC and vimentin, alpha-actinin, and vinculin suggests that PKC participates actively in the transduction of mechanical signals to the cell through focal adhesions and the cytoskeleton, although only PKC seemed to change with short time periods of strain. In conclusion, dentoalveolar osteoblasts responded to mechanical strain initially through increases in levels of IP3, PKC activity, and later cAMP, and this response was potentiated when PTH was applied together with mechanical strain.


Independence of data points in the measurement of hand preferences in primates: statistical problem or urban myth?
Lack of independence of data points or the pooling fallacy has been suggested as a potential problem in the study of handedness in nonhuman primates, particularly as it relates to whether hand use responses should be recorded as individual events or bouts of activity. Here, I argue that there is no evidence that the concept of statistical independence of data points or the pooling fallacy is a problem in the evaluation of population-level handedness in previous studies in nonhuman primates. I further argue these statistical concepts have been misapplied to the characterization of individual hand preferences. Finally, I argue that recording hand use responses as bouts rather than events has no significant effect on reports of hand use in nonhuman primates and, in fact, may unintentionally bias hand use toward the null hypothesis. Several suggestions for improvement in the measurement and statistical determination of individual handedness are offered in the article.


Adaptive immune responses are altered in adult mice following neonatal hyperoxia.
Premature infants with bronchopulmonary dysplasia (BPD), are at risk for frequent respiratory infections and reduced pulmonary function. We studied whether neonatal hyperoxia disrupts adaptive immune responses in adult mice, contributing to higher respiratory-related morbidities seen in these infants. Newborn mice litters were randomized at 3 days to 85% O2 or room air (RA) for 12 days. Whole lung mRNA was isolated in both the groups at 2 weeks and 3 months. Gene expression for T-cell and B-cell adaptive immune response was performed by real-time PCR and qRT-PCR; protein expression (p21, IL4, IL10, IL27, cd4) was performed by enzyme immunoassay along with p21 immunohistochemistry. Hyperoxia increased expression of p21 and decreased expression of 19 genes representing T/B-cell activation by ≥ fourfold; three of them significantly (Rag1, Cd1d1, Cd28) compared to the RA group at 2 weeks. Despite RA recovery, the expression of IFNγ, IL27, and CD40 was significantly reduced at 3 months in the hyperoxia group. Expression of p21 was significantly higher and IL27 protein lower at 2 weeks following hyperoxia. Adult mice exposed to neonatal hyperoxia had lower IL4 and IL10 in the lung at 3 months. Adaptive immune responses are developmentally regulated and neonatal hyperoxia suppresses expression of genes involved in T-/B-cell activation with continued alterations in gene expression at 3 months. Dysfunction of adaptive immune responses increases the risk for susceptibility to infection in premature infants.


Flow cytometry: past and future.
Flow cytometry is a single-cell technology that measures scatter and fluorescence to establish a set of unique cellular properties. Flow cytometry is used in many areas of science, in particular biotechnology and medicine, but also in industrial applications. Flow cytometry can identify multiple phenotypic subsets from a mixture, select a single cell and even isolate that cell by a process called cell sorting. The field is currently undergoing dramatic changes. We are moving rapidly from the polychromic flow cytometry that has been the go-to technology for 45 years to spectral flow cytometry, which is now the most significant change in nearly half a century of flow cytometry. With change comes opportunity. Even spectral flow cytometry will morph into second-generation spectral flow cytometry within 5 years. New, exciting features will open up molecular diagnostics and physiology to flow cytometry.


The effect of voxel size on the measurement of mandibular thickness in cone-beam computed tomography.
Cone-beam computed tomography (CBCT) is a new imaging technology that has been widely used in implantology, oral and maxillofacial surgery and orthodontics. This method provides 3-D images that are composed of voxel, which is the smallest image unit, and determines image resolution. Smaller voxel is associated with the higher resolution and also greater radiation exposure. This study was aimed to find out the effect of voxel size on the measurement of mandibular thickness. Using voxel sizes of 0.30 mm and 0.15 mm, two CBCT protocols (protocol 1: Field of view (FOV) of 15 cm, 85 kVp, 42 mAs, 0.15 mm voxel, 14 s scan time; protocol 2: FOV of 15 cm, 85 kVp, 10 mAs, 0.30 mm voxel, 14 s scan time) were carried out on 16 dry human mandibles with permanent dentition. Mandibular thickness was measured at seven different sites (midline region, bilateral canine regions, bilateral mental foramen regions and bilateral molar regions). Analysis of variance was used for analysis of data using the Statistical Package for the Social Sciences version 20 (SPSS Inc., Chicago, IL, USA). P < 0.05 considered to be statistically significant. No statistically significant differences were found between different protocols regarding the mandibular thickness (P > 0.05). Considering the insignificant differences of the mandibular thickness measurements using different voxel sizes, it would be more reasonable to use 0.30 mm voxel size instead of 0.15 mm voxel size to avoid unnecessary radiation exposure.


Effects of DNA charge and length on the electrophoretic mobility of intercalated DNA.
DNA molecules ranging in size from 1 to 630 kilobase pair and intercalated with either ethidium bromide (EtBr) or propidium iodide (PI) were electrophoresed in 1% agarose at four different electric field strengths. The extent of intercalation of EtBr under the conditions of our electrophoresis experiments was determined by a spectroscopic technique, whereas the extent of intercalation of PI was inferred from previous studies. The effects of the increase in DNA contour length and the concomitant decrease of linear charge density were separated based on our analysis of the mobility data. We conclude that the main factor responsible for the reduced electrophoretic mobility of intercalated DNA is the diminished linear charge density and not the increased contour length.


Physical activity among adults >or=50 yr with and without disabilities, BRFSS 2001.
Before 2001, the Behavioral Risk Factor Surveillance System (BRFSS), a national survey of health behaviors, assessed only leisure-time physical activity. In 2001, the BRFSS used newly developed physical activity items to evaluate combined leisure-time, household, and transportation activities. Using BRFSS 2001 data, this cross-sectional study describes the prevalence of inactivity and insufficient and recommended physical activity for older adults (i.e., aged >or=50 yr). BRFSS 2001 data were analyzed using prevalence estimates and logistic regression to assess physical activity patterns among older adults (N=74,960) stratified by disability status, and select sociodemographic and health status characteristics. A total of 43.4, 39.1, and 17.5% of respondents without disabilities were active at a recommended level, insufficiently active, and inactive, respectively, taking into account nonoccupational physical activities. A total of 28.8% of older adults with disabilities were active at a recommended level, 35.7% insufficiently active, and 35.5% inactive. Among persons with and without disabilities, groups with the highest odds of inactivity and insufficient activity were women, persons aged >or=75 yr, blacks, persons with lower education levels and low incomes, and those who were obese. Not all persons with disabilities can be active at recommended levels, but it is possible for the vast majority to do some types of physical activity, even if at insufficient levels. Thus, it may be possible for the prevalence of inactivity among persons with and without disabilities to be similar. This was not found. At the start of the new millennium, almost 60% of older adults without disabilities and 70% with disabilities were not obtaining a recommended amount of combined leisure-time, transportation, and household physical activity.


Management of women with ductal carcinoma in situ of the breast: a population-based study.
Increasing incidence of ductal carcinoma in situ (DCIS) confronts patients and clinicians with optimal treatment decisions. This multidisciplinary study investigates therapeutic modalities of DCIS in daily practice and provides recommendations on how to increase quality of care. All women (n = 116) with unilateral DCIS recorded in the Geneva Cancer Registry from 1995 to 1999 were considered. Information concerned patient and tumor characteristics, treatment and outcome. Factors linked to therapy were determined using a case-control approach. Cases were women with treatment of interest and controls other women on the study. Most DCIS cases (62%) were discovered by mammography screening. Ninety (78%) women had breast-conserving surgery (BCS), 18 (16%) mastectomy and seven (6%) bilateral mastectomy. Eight (7%) patients had tumor-positive margins, 18 (16%) lymph node dissection and two (1.7%) chemotherapy. Twenty-five per cent of women with BCS had no radiotherapy, three had radiotherapy after mastectomy. Less than 50% underwent breast reconstruction after mastectomy. Method of discovery, multifocality, tumor localization, size and differentiation were linked to the use of BCS or lymph node dissection. Because of important disparities in DCIS management, recommendations are made to increase quality of care, in particular to prevent axillary dissection or bilateral mastectomy and to increase the use of radiotherapy after BCS.


Two-Year Agility Maintenance Training Slows the Progression of Parkinsonian Symptoms.
Parkinson's disease (PD) is a progressive neurodegenerative condition and it is unclear if long-term nonpharmaceutical interventions can slow the progression of motor and nonmotor symptoms and lower drug dose. In a randomized trial, after an initial 3-wk-long, 15-session supervised high-intensity sensorimotor agility exercise (E) program designed to improve postural instability, the exercise+maintenance (E + M, n = 19) group continued to exercise three times per week for 2 yr, whereas E (n = 16), and the no exercise and no maintenance control (C, n = 20) continued habitual living. Eight outcomes were measured before and after the 3-wk initial exercise program and then at 3, 6, 9, 12, 18, and 24 months in all patients. The group-time interactions (all P < 0.005) revealed robust and favorable effects of the initial 3-wk agility program on all six nonmotor (e.g., primary outcome Movement Disorder Society Unified Parkinson Disease Rating Scale, Motor Experiences of Daily Living, ~7 points; EuroQoL, ~9 points) and on each of the two motor outcomes (timed up and go test: ~6 s; posturography: up to 7 mm improvements in center of pressure path). E + M maintained but did not further improve the benefits produced by the initial 3-wk program. In E, the favorable effects of the 3-wk agility program lasted for 3 to 12 months. In C, patients declined steadily in all outcomes over 2 yr. By year 2, Leva-dopa equivalents increased by 99.4 mg·d (time main effect, P = 0.008). A high-intensity sensorimotor agility program with but not without a 2-yr maintenance program slowed the progression of parkinsonian symptoms.


Spatial, temporal and socioeconomic patterns of illicit drug use in New Zealand assessed using wastewater-based epidemiology timed to coincide with the census.
A discrete experiment in wastewater-based epidemiology (WBE) timed to coincide with the census was used to investigate the spatial, temporal and socioeconomic patterns of illicit drug consumption in Auckland, Bay of Plenty and Canterbury. For seven consecutive days over census week (6 March 2018), wastewater was sampled from seven wastewater treatment plants and analysed for methamphetamine, cocaine (as benzoylecgonine) and 3,4-methylenedioxymethamphetamine (MDMA). Detailed sewer catchment maps were developed and, together with the data, were used to analyse drug consumption. Methamphetamine (mean 22.9 ± 9.9 doses/day/1000 people) was the most consumed drug, followed by MDMA (mean 1.7 ± 1.5 doses/day/1000 people) and cocaine (mean 0.5 ± 0.3 doses/day/1000 people). Methamphetamine consumption (and to a lesser extent MDMA) was high compared to that reported for Western nations, while cocaine consumption was extremely low. Cocaine and MDMA consumption were higher in cities compared to towns. In contrast, methamphetamine was typically higher in towns. Cocaine and MDMA were consumed more at weekends. Methamphetamine use was more consistent throughout the week. MDMA and cocaine were correlated with socioeconomic advantage, whereas methamphetamine was correlated with disadvantage. This paper contextualises illicit drug use in three New Zealand regions containing 18.3% of the national population and confirms the pervasiveness of methamphetamine consumption in New Zealand towns. This work demonstrates how WBE can be used to explore the socioeconomic dimensions of drug use when duly combined with other data sources like censuses.