Association of crown-rump length at 11 to 14 weeks' gestation and risk of a large-for-gestational-age neonate.
The purpose of this study was to evaluate the association between crown-rump length (CRL) and the risk of a large-for-gestational-age (LGA) neonate. Data were retrospectively collected on consecutive women with a healthy singleton pregnancy followed to delivery at our center from 2003 to 2006 who underwent nuchal translucency, pregnancy-associated plasma protein-A, and free beta-human chorionic gonadotropin screening at 11 to 14 weeks' gestation. Pregnancies were dated by the last menstrual period (LMP) confirmed by CRL at 6 to 10 weeks or the known time of fertilization. The fetal CRL at 11 to 14 weeks was obtained from frozen sonographic images. The measured CRL was converted to gestational weeks using the method of Hadlock et al (Radiology 1992; 182:501-505). The expected gestational age (GA) by the LMP was subtracted from the measured GA to yield the DeltaCRL. The association between the DeltaCRL and birth weight was statistically analyzed. The sample included 521 women. Fifty neonates (9.6%) were LGA (>or=90th percentile), 38 (7.3%) small for gestational age, and 433 (83.1%) appropriate for gestational age. The LGA group was characterized by significantly larger-than-expected CRL measurements (P = .033). The birth weight percentile and rate of LGA neonates were significantly higher in pregnancies in which the DeltaCRL was 1/2 week or greater (P = .007 and .033, respectively). There was a significant linear correlation between the DeltaCRL and birth weight percentile (P = .001). On multivariate logistic regression analysis, the DeltaCRL was the only significant predictor of an LGA neonate (odds ratio, 1.6; 95% confidence interval, 1.07-2.4; P = .023). Pregnancies with LGA neonates are characterized by larger-than-expected CRL measurements at 11 to 14 weeks' gestation.


Candida glabrata ATP-binding cassette transporters Cdr1p and Pdh1p expressed in a Saccharomyces cerevisiae strain deficient in membrane transporters show phosphorylation-dependent pumping properties.
The expression and drug efflux activity of the ATP binding cassette transporters Cdr1p and Pdh1p are thought to have contributed to the recent increase in the number of fungal infections caused by Candida glabrata. The function of these transporters and their pumping characteristics, however, remain ill defined. We have evaluated the function of Cdr1p and Pdh1p through their heterologous hyperexpression in a Saccharomyces cerevisiae strain deleted in seven major drug efflux transporters to minimize the background drug efflux activity. Although both Cdr1p- and Pdh1p-expressing strains CDR1-AD and PDH1-AD acquired multiple resistances to structurally unrelated compounds, CDR1-AD showed, in most cases, higher levels of resistance than PDH1-AD. CDR1-AD also showed greater rhodamine 6G efflux and resistance to pump inhibitors, although plasma membrane fractions had comparable NTPase activities. These results indicate that Cdr1p makes a larger contribution than Phd1p to the reduced susceptibility of C. glabrata to xenobiotics. Both pump proteins were phosphorylated in a glucose-dependent manner. Whereas the phosphorylation of Cdr1p affected its NTPase activity, the protein kinase A-mediated phosphorylation of Pdh1p, which was necessary for drug efflux, did not. This suggests that phosphorylation of Pdh1p may be required for efficient coupling of NTPase activity with drug efflux.


Efficacy of isometric exercise full knee extension horizontally (FKEH)--a new and simple maneuver to predict early onset of hypertension.
Hypertension is recognized as one of the risk factors for cardiovascular mortality and morbidity. Early identification of persons at increased risk for developing hypertension is a priority, which help them, to live a healthy life by altering lifestyle. Persons having predisposing factors of hypertension (e.g., family history of hypertension) show blood pressure hyper-responsiveness to stress. Elevated blood pressure due to sympathetic stimulation prevailed longer time in susceptible persons. In previous studies some instruments (e.g., hand immersion in cold (4 degrees C) water or isometric exercise by handgrip dynamometer) were required to elicit sympathetic stimulation. In the present study a simple maneuver Full Knee Extension Horizontally (FKEH) has been introduced--a stressor that caused full isometric contraction of quadriceps femoris muscles of both sides. The test was conducted in normotensive, non-smoker males (n = 150) of age group 18-25 years. Among them some (n = 100) were from families having no history of familial hypertension and others (n = 50) were from the families with history of hypertension. The causal blood pressure and heart rate of the participants were recorded. Then the volunteers were requested to perform FKEH maneuver for one minute. Both blood pressure and heart rate were recorded immediately after and 3 minutes following FKEH. The data analyzed using t-test showed that, diastolic blood pressure didn't return and stabilized to pre-exercise level even after 3 minutes following FKEH in volunteers who were mostly from hypertensive family (P< 0.05) i.e., having predisposing factors of hypertension. This indicated those people are prone to early onset of hypertension as their Autonomic Nervous System (ANS) is not competent enough to stabilize their blood pressure to pre-exercise level. Hence, stress in the form of FKEH for one minute may be used as a bedside test to assess the competence of ANS and the proneness of developing early hypertension.


Cerebellar input to the posterior parietal cortex in the rat.
The cerebello-thalamo-parietal projections were investigated in rats by means of a multiple anterograde-retrograde tracing technique. Retrograde fluorescent tracers were injected in different loci of the parietal cortex. Injected areas were verified cytoarchitectonically and confirmed by analyzing the retrograde thalamic labeling pattern obtained. Anterograde fluorescent tracers were placed in the intermediate and lateral deep cerebellar nuclei. The topographical overlap between cerebellar terminals and parietal-projecting thalamic neurons was analyzed. In the central lateral (CL) and ventrolateral (VL) thalamic nuclei, cells projecting to anterior somatosensory (S1) and posterior parietal (PPC) cortices were demonstrated to receive direct cerebellar input. In particular, two patterns of organization were revealed. In CL, the PPC- and S1-projecting neurons, both receiving cerebellar fibers, were intermingled. In VL, PPC, and S1-projecting neurons were instead segregated, and the areas containing labeled neurons received separate contingents of cerebellar fibers. These patterns suggest that in CL axons originating from the same or neighboring cerebellar neurons can terminate on both PPC- and S1-projecting neurons, while in VL cerebellar information is funneled to S1 and PPC through two segregated parallel pathways. The significance of the observed organization is discussed comparing findings in other species and in relation with electrophysiological and functional studies on cerebelloparietal interrelationships.


Acute fracture of the femoral neck: assessment of femoral head perfusion with gadopentetate dimeglumine-enhanced MR imaging.
Evaluation of the perfusion and viability of the femoral head after fracture of the femoral neck is important because the outcome of conservative treatment or joint-preserving surgery is adversely affected by the development of capital osteonecrosis. We evaluated the use of MR imaging, before and after IV administration of gadopentetate dimeglumine, for assessing perfusion of the femoral head in 13 patients with acute fracture of the femoral neck. Multiecho (1600/30-240 [TR/TE]) MR images were obtained before contrast administration and gradient-echo (315/14, 90 degrees flip angle) MR images were obtained both before and after contrast administration. MR findings were correlated with findings on superselective digital subtraction angiograms of the vessels supplying the femoral head and with clinical-radiographic follow-up for at least 12 months. Digital subtraction angiography showed impaired blood supply to the femoral head in five patients. On contrast-enhanced MR images of these patients, the femoral head did not enhance and was lower in signal intensity than were the enhancing femoral shaft and neck distal to the fracture and the enhancing femoral head on the unaffected side. In the patients with persistent perfusion, contrast-enhanced MR images showed a uniform increase in signal intensity in the femoral shaft and neck as well as the femoral head; the femoral head on the fractured side showed contrast enhancement similar to that on the healthy side. These preliminary results indicate that contrast-enhanced MR imaging may be useful for noninvasive evaluation of femoral head perfusion after fracture of the femoral neck. MR findings also may aid the clinician in deciding between joint-preserving therapy and hip arthroplasty.


Gas chromatography/time-of-flight mass spectrometry-based metabonomics of hepatocarcinoma in rats with lung metastasis: elucidation of the metabolic characteristics of hepatocarcinoma at formation and metastasis.
Hepatocarcinoma (HCC) has a very high mortality rate and the high recurrence and metastasis rates contribute to the poor prognosis of HCC patients. To understand HCC formation and metastasis, we assessed the metabonomics of rat HCC and HCC with lung metastasis (HLM). The HLM rat model was established by exposure to diethylnitrosamine (DEN). Levels of serum and urine metabolites were quantified with gas chromatography/time-of-flight mass spectrometry (GC/TOFMS), and data were analyzed with partial least-squares discrimination analysis (PLS-DA). Serum and urine levels of some metabolites differed significantly between the control, HCC, and HLM groups. The products and intermediates from glycolysis and glutamate metabolism were elevated, while the tricarboxylic acid (TCA) cycle was inhibited, in both HCC and HLM. HLM samples revealed enhanced metabolism of nucleic acids, amino acids and glucuronic acid. PLS-DA indicated that principal component weighting was greatest for serum serine, phenylalanine, lactic acid, tyrosine and glucuronic acid, and urine glycine, serine, 5-oxyproline, malate, hippuric acid and uric acid. These data provide novel information that will improve understanding of the pathophysiological processes involved in HCC and HLM, and revealed potential metabolic markers for HCC invasion and metastasis.


Psychosis in Borrelia burgdorferi infection - part I: epidemiology, pathogenesis, diagnosis and treatment of neuroborreliosis.
Borreliosis is a multisystem, bacterial, zoonotic infectious disease with diversified spectrumof symptoms, which may also include psychotic disorders. Clinical picture of the disease is often unspecific, which makes the diagnosis relatively difficult. Uncharacteristic process of borreliosis is a result of complex molecular strategies used by spirochetes to infect, disseminate and survive in host organism. Part I of the article is focused on the current knowledge about pathogenesis of Lyme Borreliosis (LB), especially neuroborreliosis. Additionally, epidemic situation in Poland and in Europe was presented. Also, typical clinical manifestations of LB were described. In the article, the crucial pathogenic cell mechanisms were depicted. The processes of infection and dissemination of Borrelia in host were presented. The most important strategies of evading the response of host immune system were also discussed. These mechanisms are probable cause of the chronic and uncharacteristic clinical picture of the disease, as they significantly impair host immune response to bacteria. Also, there were presented molecular processes of neural cells impairment, which may lead to observed clinical symptoms of neuroborreliosis. Furthermore, diagnostic methods, treatment guidelines and some of diagnostic problems were discussed.


Using a latent growth curve model for an integrative assessment of the effects of genetic and environmental factors on multiple phenotypes.
We propose the use of latent growth curve model to assess the influence of genetic, environmental, demographic, and lifestyle factors on multiple phenotypes related to coronary heart disease. We model four quantitative traits (systolic blood pressure, high-density lipoprotein, low-density lipoprotein, and triglycerides) simultaneously in a multivariate framework that allows us to study their change over time, assess individual variation, and investigate cross-phenotype relationships. Environmental, demographic, and lifestyle covariates are included at different levels of the model as time-varying or time-invariant, as appropriate. To investigate the change over time attributed to genetic factors, we use candidate markers that have previously been shown to be associated with the quantitative traits. We illustrate our approach using independent observations from the offspring cohort of the Framingham Heart Study data.


Mechanistic Exploration of the Competition Relationship between a Ketone and C═C, C═N, or C═S Bond in the Rh(III)-Catalyzed Carbocyclization Reactions.
The introduction of a C═O, C═C, C═S, or C═N bond has emerged as an effective strategy for carbocycle synthesis. A computational mechanistic study of Rh(III)-catalyzed coupling of alkynes with enaminones, sulfoxonium ylides, or α-carbonyl-nitrones was carried out. Our results uncover the roles of dual directing groups in the three substrates and confirm that the ketone acts as the role of the directing group while the C═C, C═N, or C═S bond serves as the cyclization site. By comparing the coordination of the ketone versus the C═C, C═N, or C═S bond, as well as the chemoselectivity concerning the six- versus five-membered formation, a competition relationship is revealed within the dual directing groups. Furthermore, after the alkyne insertion, instead of the originally proposed direct reductive elimination mechanism, the ketone enolization is found to be essential prior to the reductive elimination. The following C(sp2)-C(sp2) reductive elimination is more favorable than the C(sp3)-C(sp2) formation, which can be explained by the aromaticity difference in the corresponding transition states. The substituent effect on controlling the selectivity was also discussed.


Global energy minimization by rotational energy embedding.
Given a sufficiently good empirical potential function for the internal energy of molecules, prediction of the preferred conformations is nearly impossible for large molecules because of the enormous number of local energy minima. Energy embedding has been a promising method for locating extremely good local minima, if not always the global minimum. The algorithm starts by locating a very good local minimum when the molecule is in a high-dimensional Euclidean space, and then it gradually projects down to three dimensions while allowing the molecule to relax its energy throughout the process. Now we present a variation on the method, called rotational energy embedding, where the descent into three dimensions is carried out by a sequence of internal rotations that are the multidimensional generalization of varying torsion angles in three dimensions. The new method avoids certain kinds of difficulties experienced by ordinary energy embedding and enables us to locate conformations very near the native for avian pancreatic polypeptide and apamin, given only their amino acid sequences and a suitable potential function.


TGF-beta1 induces transendothelial migration of the pathogenic fungus Sporothrix schenckii by a paracellular route involving extracellular matrix proteins.
Sporotrichosis, a mycosis caused by Sporothrix schenckii, is characterized by lymphocutaneous lesions. In immunocompromised hosts, this fungus may invade the bloodstream and disseminate to other tissues, such as lung and bone. Our group previously showed that S. schenckii yeasts adhere to endothelial monolayers and that this interaction is modulated by cytokines. Using 3.0 mum-pore culture inserts, the present work shows that transforming growth factor (TGF)-beta1 led to a 80+/-26 % increase in fungal migration across endothelial monolayers and inhibited fungus internalization by 55+/-23.5 %, when compared to untreated cells. The major surface endothelial molecules recognized by S. schenckii were not modulated by TGF-beta1. These data suggested that a paracellular route is preferentially used by S. schenckii during the transmigration of cultured endothelial cells. It was further observed that TGF-beta1 increased the subendothelial matrix exposure and that anti-fibronectin (anti-FN) and anti-laminin (anti-LM) antibodies abolished the increase in S. schenckii association with endothelial monolayers induced by TGF-beta1. These antibodies also inhibited (38.2+/-4.29 % and 50.8+/-17.3 %, respectively) the adhesion of S. schenckii to freshly prepared native endothelial matrices. Furthermore, transendothelial migration of S. schenckii was blocked by anti-FN and anti-LM antibodies. These data indicate that TGF-beta1-induced S. schenckii adhesion to endothelial monolayers results from the increased exposure of the subendothelial extracellular matrix and that this event may contribute to the enhancement of transendothelial migration.


Novel dimeric alkaloids from the roots of Thalictrum atriplex.
Two new bisbenzylisoquinoline alkaloids, neothalfine (1) and thaliatrine (2), together with three known dimeric alkaloids, thalifaberine, thalistine, and thalirecebine, have been isolated from the roots of Thalictrum atriplex Finet et Gagnep. Their structures have been established by spectroscopy. Compound 1 showed in vitro antiplatelet aggregation activities.


Shape morphing mechanical metamaterials through reversible plasticity.
Biological organisms such as the octopus can reconfigure their shape and properties to perform diverse tasks. However, soft machines struggle to achieve complex configurations, morph into shape to support loads, and go between multiple states reversibly. Here, we introduce a multifunctional shape-morphing material with reversible and rapid polymorphic reconfigurability. We couple elastomeric kirigami with an unconventional reversible plasticity mechanism in metal alloys to rapidly (<0.1 seconds) morph flat sheets into complex, load-bearing shapes, with reversibility and self-healing through phase change. This kirigami composite overcomes trade-offs in deformability and load-bearing capacity and eliminates power requirements to sustain reconfigured shapes. We demonstrate this material through integration with onboard control, motors, and power to create a soft robotic morphing drone, which autonomously transforms from a ground to air vehicle and an underwater morphing machine, which can be reversibly deployed to collect cargo.


An Updated PAH Mutational Spectrum of Phenylketonuria in Mexican Patients Attending a Single Center: Biochemical, Clinical-Genotyping Correlations.
Establishing the genotypes of patients with hyperphenylalaninemia (HPA)/phenylketonuria (PKU, MIM#261600) has been considered a cornerstone for rational medical management. However, knowledge of the phenylalanine hydroxylase gene (PAH) mutational spectrum in Latin American populations is still limited. Herein, we aim to update the mutational PAH spectrum in the largest cohort of HPA/PKU Mexican patients (N = 124) reported to date. The biallelic PAH genotype was investigated by Sanger automated sequencing, and genotypes were correlated with documented biochemical phenotypes and theoretical tetrahydrobiopterin (BH4) responsiveness. Patients were biochemically classified as having classic PKU (50%, 62/124), mild PKU (20.2%, 25/124) and mild HPA (29.8%, 37/124). Furthermore, 78.2% of the included patients (97/124) were identified by newborn screening. A total of 60 different pathogenic variants were identified, including three novel ones (c. 23del, c. 625_626insC and c. 1315 + 5_1315 + 6insGTGTAACAG), the main categories being missense changes (58%, 35/60) and those affecting the catalytic domain (56.6%, 34/60), and c. 60 + 5G > T was the most frequent variant (14.5%, 36/248) mainly restricted (69.2%) to patients from the central and western parts of Mexico. These 60 types of variants constituted 100 different biallelic PAH genotypes, with the predominance of compound-heterozygous ones (96/124, 77%). The expected BH4 responsiveness based on the PAH genotype was estimated in 52% of patients (65/124), mainly due to the p. (Val388Met) (rs62516101) allele. Instead, our study identified 27 null variants with an allelic phenotype value of zero, with a predominance of c. 60 + 5G > T, which predicts the absence of BH4 responsiveness. An identical genotype reported in BIOPKUdb was found in 92/124 (74%) of our patients, leading to a genotype-phenotype concordance in 80/92 (86.9%) of them. The high number of variants found confirms the heterogeneous and complex mutational landscape of HPA/PKU in Mexico.


Radiological prevalence of equine odontoclastic tooth resorption and hypercementosis.
Equine odontoclastic tooth resorption and hypercementosis (EOTRH) is a painful and progressive dental disease that mainly affects the incisors and canine teeth of aged horses. Diagnosis is based on radiographs to detect early stages of the disease. EOTRH is probably underdiagnosed and its prevalence in Germany unknown. This study was performed to determine the radiological prevalence of EOTRH in a large horse population in Berlin-Brandenburg, Germany. Prevalence study. The study population (142 horses) consisted of all horses 10 years and older that were presented at the Equine Hospital for a routine dental examination. The horses were either presented as clinical cases (CC population) or belonged to a riding school (RS population). Digital radiographs of the incisor dentition were taken and evaluated for changes related to EOTRH, leading to an overall classification for each horse. The mean age of the study population was 21 years and ranged from 10 to 37 years. Overall, 94% of all horses had at least minor and 62% had moderate to severe radiological changes of the incisor teeth associated to EOTRH. No horse older than 14 years was without radiological signs of EOTRH and all horses over 28 years of age had at least moderate radiological changes of the incisor teeth. The clinical cases group might have a bias towards horses with existing dental problems such as EOTRH, because they were presented explicitly for dental care to a clinic. Focusing on radiological changes, this study shows that EOTRH is a common condition of horses in Berlin-Brandenburg. With older age, disease is more frequent and radiological changes become more severe. Since no horse older than 14 years was without radiological findings, it is likely that mild changes may be associated with the normal tooth ageing process.


Algal Feedback and Removal Efficiency in a Sequencing Batch Reactor Algae Process (SBAR) to Treat the Antibiotic Cefradine.
Many previous studies focused on the removal capability for contaminants when the algae grown in an unexposed, unpolluted environment and ignored whether the feedback of algae to the toxic stress influenced the removal capability in a subsequent treatment batch. The present research investigated and compared algal feedback and removal efficiency in a sequencing batch reactor algae process (SBAR) to remove cefradine. Three varied pollution load conditions (10, 30 and 60 mg/L) were considered. Compared with the algal characteristics in the first treatment batch at 10 and 30 mg/L, higher algal growth inhibition rates were observed in the second treatment batch (11.23% to 20.81%). In contrast, algae produced more photosynthetic pigments in response to cefradine in the second treatment batch. A better removal efficiency (76.02%) was obtained during 96 h when the alga treated the antibiotic at 60 mg/L in the first treatment batch and at 30 mg/L in the second treatment batch. Additionally, the removal rate per unit algal density was also improved when the alga treated the antibiotic at 30 or 60 mg/L in the first treatment batch, respectively and at 30 mg/L in the second treatment batch. Our result indicated that the green algae were also able to adapt to varied pollution loads in different treatment batches.


The yeast form of the fungus Candida albicans promotes persistence in the gut of gnotobiotic mice.
Many microorganisms that cause systemic, life-threatening infections in humans reside as harmless commensals in our digestive tract. Yet little is known about the biology of these microbes in the gut. Here, we visualize the interface between the human commensal and pathogenic fungus Candida albicans and the intestine of mice, a surrogate host. Because the indigenous mouse microbiota restricts C. albicans settlement, we compared the patterns of colonization in the gut of germ free and antibiotic-treated conventionally raised mice. In contrast to the heterogeneous morphologies found in the latter, we establish that in germ free animals the fungus almost uniformly adopts the yeast cell form, a proxy of its commensal state. By screening a collection of C. albicans transcription regulator deletion mutants in gnotobiotic mice, we identify several genes previously unknown to contribute to in vivo fitness. We investigate three of these regulators-ZCF8, ZFU2 and TRY4-and show that indeed they favor the yeast form over other morphologies. Consistent with this finding, we demonstrate that genetically inducing non-yeast cell morphologies is detrimental to the fitness of C. albicans in the gut. Furthermore, the identified regulators promote adherence of the fungus to a surface covered with mucin and to mucus-producing intestinal epithelial cells. In agreement with this result, histology sections indicate that C. albicans dwells in the murine gut in close proximity to the mucus layer. Thus, our findings reveal a set of regulators that endows C. albicans with the ability to endure in the intestine through multiple mechanisms.


Involvement of apoptosis in ovarian follicular atresia and postovulatory regression.
In the ovary, greater than 99% of the follicles present at birth are destined to degenerate during life. In humans, less than 400 of the more than 400,000 follicles found at puberty will eventually ovulate whereas the overwhelming majority of follicles undergo atresia. Although follicular atresia plays a critical role during the recruitment of follicles for ovulation, the exact mechanism of this process is unknown. In chicken and porcine ovaries, atretic follicles can be morphologically distinguished from their healthy counterparts of the same size. Adapting a sensitive 3'-end labeling method for DNA analysis, we identified internucleosomal cleavage of cellular DNA in atretic (but not normal) follicles of both animal species, resembling that found during programmed cell death in embryogenesis, autoimmune T-cell removal and prostate regression. The present findings provide a basis for elucidating the hormonal signals involved in the initiation of follicular atresia during follicle recruitment, reproductive aging and premature ovarian failure.


A novel duplication of chromosome (13)(q14.1q21.3) in a patient with mental retardation and microcephaly.
We report on a mentally retarded female with behavioural problems, microcephaly, mild facial dysmorphisms, short stature and small hands with thin fingers due to a de novo partial duplication within the long arm of chromosome 13(q14.1q21.3). She was primarily referred to the outpatient department of neuropsychiatry because of short lasting psychotic episodes. No formal psychiatric diagnosis was made and the behavioural problems appeared the result of anxieties provoked by novel situations, enhanced by the intellectual disability. To the author's knowledge, this duplication has not been published previously and it is considered causative of the phenotype.


Characterization of the Acinetobacter baumannii growth phase-dependent and serum responsive transcriptomes.
Acinetobacter baumannii has emerged as a bacterial pathogen of considerable healthcare concern. Yet, little is known about the organism's basic biological processes and the regulatory networks that modulate expression of its virulence factors and antibiotic resistance. Using Affymetrix GeneChips , we comprehensively defined and compared the transcriptomes of two A. baumannii strains, ATCC 17978 and 98-37-09, during exponential and stationary phase growth in Luria-Bertani (LB) medium. Results revealed that in addition to expected growth phase-associated metabolic changes, several putative virulence factors were dramatically regulated in a growth phase-dependent manner. Because a common feature between the two most severe types of A. baumannii infection, pneumonia and septicemia, includes the organism's dissemination to visceral organs via the circulatory system, microarray studies were expanded to define the expression properties of A. baumannii during growth in human serum. Growth in serum significantly upregulated iron acquisition systems, genes associated with epithelial cell adherence and DNA uptake, as well as numerous putative drug efflux pumps. Antibiotic susceptibility testing verified that the organism exhibits increased antibiotic tolerance when cultured in human serum, as compared to LB medium. Collectively, these studies provide researchers with a comprehensive database of A. baumannii's expression properties in LB medium and serum and identify biological processes that may contribute to the organism's virulence and antibiotic resistance.


SRS-22r legacy scores can be accurately translated to PROMIS scores in adult spinal deformity patients.
Patient-Reported Outcomes Measurement Information System (PROMIS) facilitates comparisons of treatment effectiveness across populations and diseases. In adult spinal deformity (ASD), the disease-specific Scoliosis Research Society-22r (SRS-22r) tool assesses outcomes. Existing data must be translated to PROMIS to make comparisons. To develop and validate a method to translate SRS-22r scores to PROMIS scores in surgical ASD patients. Retrospective cohort study. A total of 158 ASD surgery patients from an ongoing registry of patients who underwent spine surgery at a tertiary care center from 2015 to 2017 were included. PROMIS and SRS-22r questionnaires were completed at 387 visits (150 preoperative [derivation sample]; 237 postoperative [validation sample]). Using the derivation sample, we modeled PROMIS domains as functions of age and SRS-22r domains using linear regression. The most parsimonious model was selected. In the validation cohort, we used the derived regression equations to estimate PROMIS scores from SRS-22r scores. The following significant associations were found (p<.001): PROMIS Pain Interference is dependent on age and SRS-22r Pain, Physical Function, and Patient Satisfaction; PROMIS Physical Function is dependent on age and SRS-22r Pain and Physical Function; PROMIS Anxiety is dependent on SRS-22r Mental Health; PROMIS Depression is dependent on age and SRS-22r Mental Health; and PROMIS Satisfaction with Social Roles is dependent on age and SRS-22r Pain, Physical Function (p=.011), Mental Health, and Patient Satisfaction. Correlations were strong to very strong between estimated and actual PROMIS scores in the validation cohort (p<.001): Pain Interference, r=0.78; Physical Function, r=0.66; Anxiety, r=0.83; Depression, r=0.80; and Satisfaction with Social Roles, r=0.71. PROMIS scores estimated from SRS-22r scores using our model correlate strongly with actual PROMIS scores. SRS-22r scores may be translated to PROMIS scores in all evaluated domains for ASD patients. Orthopedic surgeons can use this method to compare legacy measures with PROMIS scores.


Determinants of substrate and cation affinities in the Na+/dicarboxylate cotransporter.
The Na+/dicarboxylate cotransporter (NaDC-1) couples the transport of sodium and tricarboxylic acid cycle intermediates, such as succinate and citrate. The rabbit and human homologues (rbNaDC-1 and hNaDC-1, respectively) are 78% identical in amino acid sequence but exhibit several differences in their functional properties. rbNaDC-1 has a greater apparent affinity for citrate and sodium than hNaDC-1. Furthermore, unlike hNaDC-1, rbNaDC-1 is inhibited by low concentrations of lithium. In this study, chimeric transporters were constructed to identify the protein domains responsible for the functional differences between rbNaDC-1 and hNaDC-1. Individual substitutions of transmembrane domain (TMD) 7, 10 or 11 produced transporters with intermediate properties. However, substitution of TMD 7, 10, and 11 together resulted in a transporter with the citrate Km of the donor, suggesting that interactions between these domains determine the differences in apparent citrate affinities. TMDs 10 and 11 are most important in determining the differences in apparent sodium affinities, and TMD 11 determines the sensitivity to lithium inhibition. We conclude that transmembrane domains 7, 10, and 11 in NaDC-1 may contain at least one of the cation binding sites in close proximity to the substrate binding domain.


Intracellular sensors of extracellular bacteria.
Initial recognition of bacteria by the innate immune system is thought to occur primarily by germline-encoded pattern recognition receptors (PRRs). These receptors are present in multiple compartments of host cells and are thus capable of surveying both the intracellular and extracellular milieu for bacteria. It has generally been presumed that the cellular location of these receptors dictates what type of bacteria they respond to: extracellular bacteria being recognized by cell surface receptors, such as certain Toll-like receptors, and bacteria that are capable of breaching the plasma membrane and entering the cytoplasm, being sensed by cytoplasmic receptors, including the Nod-like receptors (NLRs). Increasingly, it is becoming apparent that this is a false dichotomy and that extracellular bacteria can be sensed by cytoplasmic PRRs and this is crucial for controlling the levels of these bacteria. In this review, we discuss the role of two NLRs, Nod1 and Nod2, in the recognition of and response to extracellular bacteria.


The Minnesota SimSmoke Tobacco Control Policy Model of Smokeless Tobacco and Cigarette Use.
A previous Minnesota SimSmoke tobacco control policy model is extended to more recent years and to include smokeless tobacco use. Using data from the 1993 Tobacco Use Supplement and information on state policies, the Minnesota SimSmoke model was updated and extended to incorporate smokeless tobacco (both exclusive and dual use) and smokeless tobacco-attributable deaths. The model was then validated against the 2002, 2006/2007, and 2014/2015 Tobacco Use Supplement and the 1999, 2007, 2014, and 2018 Minnesota Adult Tobacco Survey and used to estimate the impact of policies implemented between 1993 and 2018. Analysis was conducted in April 2019. The model validated well for cigarette and earlier smokeless tobacco use, but it predicted smokeless tobacco use less well in recent years. The model projected that male (female) smoking prevalence was 35% (36%) lower in relative terms by 2018 and 43% (44%) lower by 2040 owing to policies, with lesser reductions projected for male smokeless tobacco use. Tobacco-attributable deaths were reduced by 7,800 by 2018 and 46,900 by 2040. Price increases, primarily through taxes, were projected to have had the greatest impact on cigarette use followed by smoke-free air laws, cessation treatment policies, tobacco control campaign expenditures, and youth access enforcement. Similar effects were projected for smokeless tobacco use, except that smoke-free air laws had smaller effects. As cigarettes remain the dominant form of nicotine delivery product, cigarette-oriented policies may be an effective means of reducing the use of all nicotine delivery products. However, noncigarette-oriented policies may also play an important role.


VIP-ergic and cholinergic innervations in internal carotid arteries of the cat and rat.
Using immunohistochemical methods, choline acetyltransferase and vasoactive intestinal polypeptide immunoreactive (ChAT-I and VIP-I) fine fibers with varicosity-like structures were observed in the rat and cat cerebral arteries. Acetylcholine (ACh) induced dual responses in endothelium-intact internal carotid arteries of the cat; it induced vasodilation at low concentrations and constrictions at high concentrations (greater than 10(-6) M). ACh induced contraction exclusively in endothelium-rubbed preparations. Atropine (10(-7) M) blocked ACh-induced constriction and dilatation. ACh-induced vasodilation was potentiated by M & B 22,948 (2 x 10(-5) M), a selective cyclic GMP phosphodiesterase inhibitor. Vasoconstriction induced by ACh was inhibited by neomycin (3 x 10(-3) M), an inositol phosphate synthesis inhibitor, which did not affect the neuropeptide Y-induced contraction. VIP-induced dilation of the cat internal carotid arteries was not affected by removing the endothelial layer, but was blocked by VIP receptor antagonist ([Ac-Tyr1, D-Phe2]-GRF 1-29 amide) and potentiated by cilostazol (2 x 10(-5) M), a selective cyclic AMP phosphodiesterase inhibitor. These results are consistent with previous findings that cerebral blood vessels receive cholinergic and VIP-ergic innervations, and that ACh-induced endothelium-dependent vasodilation is mediated by cyclic GMP synthesis, and that VIP-induced endothelium-independent vasodilation is mediated by cyclic AMP synthesis. The present study, however, demonstrates for the first time the presence of varicosity-like structure associated with ChAT-I fibers, suggesting the presence of cholinergic nerve terminals and that ACh-induced cerebral vasoconstriction is mediated by phosphatidyl-inositide turnover.


Short- and long-term outcome of severe neonatal nonhemolytic hyperbilirubinemia.
We studied the effects of hyperbilirubinemia on brainstem auditory pathways and neurodevelopmental status in 99 full-term neonates with severe nonhemolytic hyperbilirubinemia (total serum bilirubin level = 301 to 500 micromol/L) born between 1995 and 2000. These were divided into three groups: group 1, moderate hyperbilirubinemia (n = 30; mean maximum total serum bilirubin = 320.7 micromol/L or 18.9 mg%); group 2, severe hyperbilirubinemia (n = 63; mean maximum total serum bilirubin = 369.0 micromol/L or 21.7 mg%); and group 3, super hyperbilirubinemia (n = 6; mean maximum total serum bilirubin = 457.2 micromol/L or 26.9 mg%). All received phototherapy, and three neonates also had exchange transfusion. Initial brainstem auditory evoked potentials were recorded in all at the mean age of 3.1 months (range 1-9 months). At initial assessment, only nine neonates (9.1%) had abnormal brainstem auditory evoked potentials. All except two returned to normal at 2 years. These two children had a hearing threshold at 50 nHL. We then compared serial brainstem auditory evoked potentials until 2 years for these nine cases with initial abnormal brainstem auditory evoked potentials, and nine cases with initial normal brainstem auditory evoked potentials were recruited for comparison. All 99 children had regular physical, neurologic, visual, and auditory assessments every 3 to 6 months until the age of 3 years. There was no significant correlation between demographic factors (gender, gestational age, or birthweight), maximum total serum bilirubin, and total serum bilirubin at discharge with an abnormal brainstem auditory evoked potential. There was no significant difference in the rate of brainstem auditory evoked potential abnormalities between the three groups: moderate (10%), severe (7.9%), and super (16.7%). All had normal neurodevelopmental status at 3 years. Only two children had transient mild motor delay and hypotonia, and both had normal brainstem auditory evoked potentials. There was no relationship between the abnormalities of the brainstem auditory evoked potentials and neurodevelopmental status. None of the three children receiving exchange transfusion had abnormal brainstem auditory evoked potentials or neurodevelopmental outcome. With the neurophysiologic and clinical outcomes in our cohort with severe nonhemolytic hyperbilirubinemia, we propose that the toxic effect of hyperbilirubinemia on auditory brainstem pathways might be transient provided that prompt treatment is initiated.


Endogenous population growth and the exploitation of renewable resources.
The authors consider a demo-economic model where the economy consists of two sectors ("hunting and farming" and "industry"), and both sectors depend directly or indirectly on the explanation of a renewable resource. The primary sector harvests a renewable resource (fish, corn, or wood) which is used as the input into industrial production, the secondary sector of our economy. Labor is divided up between these two sectors under the assumption of competitive labor markets. A system of two nonlinear differential equations for the resources and the population is studied by phase space analysis. Using the Hopf bifurcation theorem, the authors obtain two different routes to limit cycles and prove numerically the existence of a stable Malthusian limit cycle.


A pathogenic and clonally expanded B cell transcriptome in active multiple sclerosis.
Central nervous system B cells have several potential roles in multiple sclerosis (MS): secretors of proinflammatory cytokines and chemokines, presenters of autoantigens to T cells, producers of pathogenic antibodies, and reservoirs for viruses that trigger demyelination. To interrogate these roles, single-cell RNA sequencing (scRNA-Seq) was performed on paired cerebrospinal fluid (CSF) and blood from subjects with relapsing-remitting MS (RRMS; n = 12), other neurologic diseases (ONDs; n = 1), and healthy controls (HCs; n = 3). Single-cell immunoglobulin sequencing (scIg-Seq) was performed on a subset of these subjects and additional RRMS (n = 4), clinically isolated syndrome (n = 2), and OND (n = 2) subjects. Further, paired CSF and blood B cell subsets (RRMS; n = 7) were isolated using fluorescence activated cell sorting for bulk RNA sequencing (RNA-Seq). Independent analyses across technologies demonstrated that nuclear factor kappa B (NF-κB) and cholesterol biosynthesis pathways were activated, and specific cytokine and chemokine receptors were up-regulated in CSF memory B cells. Further, SMAD/TGF-β1 signaling was down-regulated in CSF plasmablasts/plasma cells. Clonally expanded, somatically hypermutated IgM+ and IgG1+ CSF B cells were associated with inflammation, blood-brain barrier breakdown, and intrathecal Ig synthesis. While we identified memory B cells and plasmablast/plasma cells with highly similar Ig heavy-chain sequences across MS subjects, similarities were also identified with ONDs and HCs. No viral transcripts, including from Epstein-Barr virus, were detected. Our findings support the hypothesis that in MS, CSF B cells are driven to an inflammatory and clonally expanded memory and plasmablast/plasma cell phenotype.


Surgical tumour margins and their significance in oral squamous cell carcinoma.
There are many prognostic indicators used to predict tumour recurrence and overall prognosis in oral squamous cell carcinoma (OSCC). Most of these biological factors cannot be directly influenced by clinicians managing these heterogeneous group of tumours. Excision margins can potentially be increased at the time of surgery by including more normal tissue than the commonly accepted 1 cm resection distance from the macroscopic tumour edge. However, this can lead to poorer quality of life for patients and does not necessarily address microscopic extensions or dicohesive patterns of tumour growth. Surgical margins can be affected by tissue shrinkage immediately following resection and the choice of instrument used for surgery. Currently, most regard a clear resection margin as being >5 mm, a close margin as more than 1 mm but <5 mm and an involved margin <1 mm. In this article, we provide a brief overview of tumour margins in OSCC, including several recently published large meta-analyses. Based upon these and other studies, there is still conflicting data in the literature about the ideal margin for OSCC. There is a growing body of evidence that suggests a clearance of 1 mm might be adequate for some cancers. However, adequacy of resection should be considered along with the many other prognostic indicators of OSCC when the multi-disciplinary team considers further treatment for these patients.


Efficacy and safety of propolis mouthwash in management of radiotherapy induced oral mucositis; A randomized, double blind clinical trial.
Propolis has been used for the management of oral mucositis in a number of studies. Due to lack of sufficient evidence especially in radiotherapy induced oral mucositis, the present study was designed to evaluate the efficacy and safety of propolis mouthwash in oral mucositis and dysphagia in patients undergoing head and neck radiotherapy. This study was a prospective, randomised, double-blind, placebo-controlled trial. The patients randomly divided into two groups receiving either the propolis or the placebo mouthwash. Patients were advised to rinse their mouth with 15 mL three times daily for four weeks. Severity of mucositis and dysphagia were evaluated by the National Cancer Institute Common Toxicity Criteria (NCI-CTC) and Common Terminology Criteria for Adverse Events (CTCAE), respectively. Thirty patients completed the study. Each group consisted of 15 patients. Although, there is not any significant difference between two groups in the first week of radiotherapy, a significant difference was seen in the second, the third and the fourth week (p = 0.03, 0.02, 0.02, respectively). Dysphagia reported as a mild score in the propolis group only in the fourth week which is significant compared with the placebo group (p = 0.01). There is not any serious adverse effect related to propolis or placebo during the study. It seems that propolis mouthwash is an effective and safe medication for alleviation of oral mucositis and dysphagia in patients under head and neck radiotherapy.


[Two cases of rare atypical localization of the petrosquamosal venous sinusis in the patients presenting with chronic suppurative epitympanitis complicated by cholesteatoma].
The authors report their original observations of rare and difficultto diagnose atypical localization of the petrosquamosal venous sinusis in the patients presenting with chronic suppurative otitis media. Such localization of this sinus was shown to hamper surgical interventions for sanative treatment.


Effects of sleep disruption on stress, nigrostriatal markers, and behavior in a chronic/progressive MPTP male mouse model of parkinsonism.
Sleep complaints are an early clinical symptom of neurodegenerative disorders. Patients with Parkinson's disease (PD) experience sleep disruption (SD). The objective of this study was to determine if preexisting, chronic SD leads to a greater loss of tyrosine hydroxylase (TH) within the striatum and the substantia nigra following chronic/progressive exposure with the neurotoxin, 1-methyl-2-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Male mice underwent chronic SD for 4 weeks, then injected with vehicle (VEH) or increasing doses of MPTP for 4 weeks. There was a significant decrease in the plasma corticosterone levels in the MPTP group, an increase in the SD group, and a return to the VEH levels in the SD+MPTP group. Protein expression levels for TH in the striatum (terminals) and substantia nigra pars compacta (dopamine [DA] cell counts) revealed up to a 78% and 38% decrease, respectively, in the MPTP and SD+MPTP groups compared to their relevant VEH and SD groups. DA transporter protein expression increased in the striatum in the MPTP versus VEH group and in the SN/midbrain between the SD+MPTP and the VEH group. There was a main effect of MPTP on various gait measures (e.g., braking) relative to the SD or VEH groups. In the SD+MPTP group, there were no differences compared to the VEH group. Thus, SD, prior to administration of MPTP, has effects on serum corticosterone and gait but more importantly does not potentiate greater loss of TH within the nigrostriatal pathway compared to the MPTP group, suggesting that in PD patients with SD, there is no exacerbation of the DA cell loss.


Identification of genes linked to gefitinib treatment in prostate cancer cell lines with or without resistance to androgen: a clue to application of gefitinib to hormone-resistant prostate cancer.
Understanding the molecular action of gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, might allow us to perform more effective therapies for hormone-independent advanced prostate cancer. A DNA microarray study was undertaken to comprehensively analyze the alteration of levels of 1,081 genes after gefitinib treatment in androgen-independent PC3 and DU145 cells and androgen-dependent LNCaP cells. The proliferation of PC3, DU145 and LNCaP cells was significantly inhibited by 50.2%, 83.8% and 55.2%, respectively, 6 days after 10 microM gefitinib administration. Of the above 1,081 genes, we identified 23, 13 and 33 genes with significantly different expression in PC3, DU145 and LNCaP cells, respectively, 24 h after 10 microM-gefitinib exposure. Among the identified genes, only Quiescin Q6, a negative cell cycle regulator, was increased after gefitinib treatment in all three cell lines regardless of gefitinib sensitivity. Except for Quiescin Q6, there were no overlapping genes between PC3 and DU145 cells. However, levels of several oncogenes or proliferation-related genes were changed after gefitinib treatment in the 2 androgen-independent cell lines. We also identified 7 unique genes [glycyl-tRNA synthetase, interferon, alpha-inducible protein, stratifin, nuclear factor of kappa light polypeptide gene enhancer in B-cells 1, dual specificity phosphatase 9, guanine nucleotide binding protein (G protein) beta polypeptide 2, neural retina leucine zipper] whose levels were altered exclusively after gefitinib administration in gefitinib-resistant PC3 and LNCaP cells, but not in DU145 cells, suggesting that these 7 genes could be targets for overcoming gefitinib resistance. Collectively, our molecular profiling data will serve as a framework for understanding the molecular action of gefitinib for prostate cancer.


Gender differences in left ventricular growth.
Because the number of human cardiac myocytes is determined in infancy, subsequent increases in left ventricular (LV) muscle mass reflect cellular enlargement (hypertrophy). To determine whether the greater LV mass in adult men than in women reflects sex differences that are present throughout development or disproportionate LV growth during puberty in men, we compared echocardiographic LV mass in 333 female and 278 male normal-weight, normotensive subjects from 4 months to 70 years of age. Only a small sex difference in LV mass (mean = 6%) existed before age 12 years, whereas in all older-age strata LV mass in men was 25% to 38% greater than that in women (P < .02 to P < .0001). The divergence in LV mass between male and female adolescents closely paralleled differences in height and weight and was due to proportional increases in LV chamber dimension and wall thickness in males (with no sex difference in relative wall thickness). LV mass grew less rapidly from infancy through childhood than did body size, assessed by body weight or height, yielding a reduction of LV mass/body size ratios up to puberty, which was followed by gradual increases during adulthood. Indexation of LV mass by body weight or height but not by body surface area or height markedly reduced the sex differences in LV mass/body size ratios from puberty through the seventh decade of life. Thus, before puberty, LV mass is only modestly higher in boys than in girls.(ABSTRACT TRUNCATED AT 250 WORDS)


Woodhouse-Sakati Syndrome Presenting With Psychotic Features After Starting Trihexyphenidyl: A Case Report.
Woodhouse-Sakati syndrome is a rare, autosomal recessive, multisystemic disorder first identified as a constellation of hypogonadism, mental retardation, diabetes, alopecia, deafness, and electrocardiogram abnormalities. We report a case of a 33-year-old woman who was born to consanguineous parents. She is suffering from hypergonadotropic hypogonadism, extrapyramidal symptoms, hypothyroidism, alopecia, and sensorineural hearing loss. Her MRI showed iron depositions in globus pallidus bilaterally. She underwent genetic testing and was diagnosed with Woodhouse-Sakati syndrome. She was started on trihexyphenidyl to treat her extrapyramidal symptoms. A few months later, she started to have psychotic symptoms in the form of auditory hallucinations and delusions of persecution. Although she exhibited psychotic symptoms after starting trihexyphenidyl, it is less likely to be causing her symptoms since the symptoms started a few months after taking the medication and she was not on high doses. Thus, it is more likely to be a part of Woodhouse-Sakati syndrome.


[Treatment of S-1 plus weekly CDDP for advanced gastric cancer].
We analyzed the clinical efficacy and safety of chemotherapy using S-1 plus weekly CDDP( w-CS therapy) for unresectable gastric cancer. Twenty one patients were treated with this treatment. S-1 80 mg/m²/day was administered for 2 weeks followed by a 1-week rest. CDDP 20 mg/m² was injected intravenously on day 1 and 8. The overall response rate was 52. 3%. The disease control rate was 85.7%. Grade 3 or 4 major toxicity comprised neutropenia (14.2%), thrombocytopenia (4.7%) and plasma creatinine elevation (4.7%). w-CS therapy is satisfied resulting with efficacy and safety. Thus, future clinical trials and accumulation of futher cases are warranted.


Magnetic resonance urography of congenital abnormalities - what the radiologist needs to know.
Congenital abnormalities of the kidney and urinary tract include a wide range of malformations ranging from asymptomatic to life-threatening conditions. Although pediatric urogenital system imaging is based on the use of US (pre- and postnatal), voiding cystourethrography and scintigraphic study, magnetic resonance (MR) urography plays a fundamental role in the classification and management of congenital abnormalities of the kidney and urinary tract, giving an overview of the different clinical pictures, thanks to its panoramicity and high anatomical detail. In fact the anomalies of the urinary tract are phenotypically variable because they can affect simultaneously several segments of different embryonic derivation, with complex clinical pictures; they can appear both as isolated phenotypes or as complex malformative conditions, involving renal parenchyma, collecting system and bladder. A deep knowledge of this complex embryogenesis and its possible phenotypic patterns allows a correct interpretation of MR urography images. We describe the embryology and pathophysiology of congenital abnormalities of the kidney and urinary tract as well as MR urography technique and findings. Congenital abnormalities of the kidney and urinary tract are classified into four groups: (1) obstruction (proximal, middle and distal), (2) budding with respect to the Wolffian duct (site and number of ureter), (3) ascent and rotation (ectopia, malrotation and fusion of kidney) and (4) anomaly of metanephric differentiation (dysplasia, megapolicalycosis).


Tyrosine phosphorylation of human urokinase-type plasminogen activator.
Immunoblotting analysis of purified human urokinase plasminogen activator (u-PA), gives a positive signal when reacted with anti-phosphotyrosine monoclonal antibodies (MoAb anti-P-Tyr); competition with o-phospho-DL-tyrosine (P-Tyr) but not o-phospho-DL-threonine or serine (P-Treo, P-Ser) completely suppresses this signal. Either the 55 kDa u-PA form and the lower Mw form (33 kDa) derived from the 55 kDa u-PA are Tyr-phosphorylated also the u-PA secreted in the culture media of human fibrosarcoma cells (HT-1080) is phosphorylated in tyrosine as well as u-PA present in tissue extracts of tumors induced in nude mice by HT-1080 cells. These data show that urine purified human u-PA and u-PA produced by human fibrosarcoma cells, in vitro and in vivo, are phosphorylated in tyrosine; furthermore our data show that u-PA is the major Tyr-phosphorylated protein present in these human tumor cells.


2-{[(4-{[(2-Hy-droxy-phen-yl)(phen-yl)methyl-idene]amino}-phen-yl)imino](phen-yl)meth-yl}phenol.
The title mol-ecule, C(32)H(24)N(2)O(2), has a crystallographically imposed inversion centre and exists in the crystal as an enol-imine tautomer. The mol-ecular structure is stabilized by two strong intra-molecular O-H⋯N hydrogen bonds. The dihedral angles between the central benzene ring and the mean planes of the phenyl substituents are 59.99 (1) and 62.79 (2)°. In the crystal, the mol-ecules are arranged into (010) layers via C-H⋯π inter-actions.


Procalcitonin as a Biomarker for a Bacterial Infection on Hospital Admission: A Critical Appraisal in a Cohort of Travellers with Fever after a Stay in (Sub)tropics.
Fever in a returned traveller may be the manifestation of a self-limiting, trivial infection but it can also presage an infection that can be rapidly progressive and lethal. We studied the diagnostic accuracy of procalcitonin (PCT) as a biomarker for a bacterial cause of fever in a cohort of 157 consecutive travellers with fever after a stay in the (sub)tropics. Elevated procalcitonin levels were observed not only in about 50% of travellers with proven bacterial infection, but also in a significant proportion of travellers with a likely infection. Using a cutoff point of 0.5 ng/mL, procalcitonin had a sensitivity of 0.52 and a specificity of 0.76 for a bacterial cause of fever on admission. Interestingly, only 1 out of 16 patients with a proven viral infection had a marginally elevated PCT concentration on admission, suggesting that an increased PCT level likely excludes a viral infection as the cause of fever. However, the diagnostic accuracy of this semiquantitative procalcitonin test for a bacterial cause of fever on admission is too poor to advocate its use in the initial clinical evaluation of fever in a setting of ill-returned travellers.


A Clinical Study Comparing the Efficacy of SesameOil with Desensitizing Tooth Paste in Reducing Dentinal Hypersensitivity: A Randomized Controlled Trial.
The objective of this study was to evaluate the efficacy of sesame oil therapy in reduction of dentin hypersensitivity, as compared to desensitizing dentifrice. Design, setting, participants. We conducted a single blinded randomized controlled trial in 100 patients reported to Diagnostic Department of King Khalid University-College of Dentistry between March 2018 and December 2019. Interventions. Patients were given desensitizing tooth paste or sesame oil to apply for the specified time. Main outcome measures. A Visual Analogue Scale was used to record sensitivity scores for controlled air stimulus and tactile method at the first visit and after 8th week of treatment. Measured outcome was reduction in dentinal hypersensitivity. Hypersensitivity degree before treatment in case of desensitizing tooth paste was 6.90 ± 1.04, and posttreatment showed a score of 4.70 ± 1.37. In case of sesame oil groups, subjects included had a score of 7.14 ± 0.90 which showed a drop to a score of 4.52 ± 1.16. Desensitizing tooth paste showed 30.5% reduction in sensitivity, whereas sesame oil application showed 36.2% reduction. The belief of considering oil therapy in oral health is just a placebo effect and may not be considered anymore. Efficacy can be established with many more studies including long follow-up and varying time periods.


Stochastic integrated model-based protocol for volume-controlled ventilation setting.
Mechanical ventilation (MV) is the primary form of care for respiratory failure patients. MV settings are based on general clinical guidelines, intuition, and experience. This approach is not patient-specific and patients may thus experience suboptimal, potentially harmful MV care. This study presents the Stochastic integrated VENT (SiVENT) protocol which combines model-based approaches of the VENT protocol from previous works, with stochastic modelling to take the variation of patient respiratory elastance over time into consideration. A stochastic model of Ers is integrated into the VENT protocol from previous works to develop the SiVENT protocol, to account for both intra- and inter-patient variability. A cohort of 20 virtual MV patients based on retrospective patient data are used to validate the performance of this method for volume-controlled (VC) ventilation. A performance evaluation was conducted where the SiVENT and VENT protocols were implemented in 1080 instances each to compare the two protocols and evaluate the difference in reduction of possible MV settings achieved by each. From an initial number of 189,000 possible MV setting combinations, the VENT protocol reduced this number to a median of 10,612, achieving a reduction of 94.4% across the cohort. With the integration of the stochastic model component, the SiVENT protocol reduced this number from 189,000 to a median of 9329, achieving a reduction of 95.1% across the cohort. The SiVENT protocol reduces the number of possible combinations provided to the user by more than 1000 combinations as compared to the VENT protocol. Adding a stochastic model component into a model-based approach to selecting MV settings improves the ability of a decision support system to recommend patient-specific MV settings. It specifically considers inter- and intra-patient variability in respiratory elastance and eliminates potentially harmful settings based on clinically recommended pressure thresholds. Clinical input and local protocols can further reduce the number of safe setting combinations. The results for the SiVENT protocol justify further investigation of its prediction accuracy and clinical validation trials.


Temporal effect of hemoglobin resuscitation on sepsis survival.
Hemoglobin (Hb)-based oxygen carriers are promising resuscitation fluids for hemorrhagic shock. However, infusion of large amounts of Hb-based material could interfere with reticuloendothelial function potentiating postresuscitation sepsis mortality. We investigated the temporal relationship between hemorrhage-resuscitation and sepsis survival. Male SD rats were subjected to hemorrhage and resuscitated with shed blood volumes of purified human hemoglobin solution (HS). Sepsis was induced by cecal ligation and puncture (CLP) 24 h before, 0, 24, or 72 h after hemorrhage/resuscitation (H/R) and survival was monitored. In additional animals with or without Hb resuscitation, hepatic heme oxygenase-1 (HO-1) gene expression and HO activity were assessed. Seven-day survival for animals resuscitated with HS prior to sepsis induction was significantly higher than other groups. Animals resuscitated with HS showed hepatic HO-1 gene expression while non-HS resuscitated animals did not. In addition, hepatic HO activity levels were significantly higher in HS resuscitated animals than non-HS resuscitated animals. In conclusion, HS resuscitation does not appear to enhance postresuscitation sepsis mortality. Rather, when conducted concomitantly or prior to sepsis, HS resuscitation appears to improve survival from a subsequent sepsis challenge.


In Professional Male Soccer Players, Time-Loss Groin Injury Is More Associated With the Team Played for Than With Training/Match-Play Duration.
To investigate the relationship between training/match-play duration and time-loss groin injury in professional male soccer players, and to determine whether previously identified intrinsic risk factors influenced this relationship. Prospective cohort study. A total of 579 professional male soccer players were prospectively followed from July 2013 to June 2015. Time-loss groin injuries and individual training and match-play duration were recorded using standardized surveillance methods. Acute training/match-play duration and chronic training/match-play duration were considered as interacting variables. Nonlinear Cox regression analysis (modeled using restricted cubic splines), clustered by player identification number, examined the relationship between training/match-play duration and groin injury. Previously identified intrinsic risk factors of previous groin injury and eccentric adduction strength were included in the multivariable regression analysis. There was no clinically meaningful relationship between training/match-play duration and groin injury risk. Team played for had the strongest influence on groin injury risk (relative log hazard ratio -2.28 to 0.97). Groin injury risk was highest when accumulated chronic and acute training duration was also highest, but large confidence intervals indicate considerable uncertainty around this finding. Previous groin injury and eccentric adduction strength were not associated with groin injury risk when training/match-play duration and team were included in the model. In professional male soccer players, there was no clinically meaningful relationship between groin injury risk and training/match-play duration. Team played for either protected against or increased groin injury risk, indicating that team-related factors not measured in this study had greater effect on groin injury risk than training/match-play duration. J Orthop Sports Phys Ther 2022;52(4):217-223. Epub 5 Feb 2022. doi:10.2519/jospt.2022.10845.


Balance Training with Wii Fit Plus for Community-Dwelling Persons 60 Years and Older.
This study sought to determine the effect of 6 weeks of training, using activities from the Nintendo(®) (Kyoto, Japan) "Wii™ Fit Plus" disc, on balance in community-dwelling Jamaicans 60 years and older. A single group pretest/posttest design was used. Thirty-three subjects enrolled and 28 completed the study. Participants completed 30-minute training sessions on the Nintendo "Wii Fit" twice per week for 6 weeks. Activities used included "Obstacle Course," "Penguin Slide," "Soccer Heading," "River Bubble," "Snow Board," "Tilt Table," "Skate Board," and "Yoga Single Tree Pose." Balance was assessed with the Berg Balance Scale, the Multi Directional Reach Test, the Star Excursion Balance Test and the Modified Clinical Test for Sensory Integration in Balance. There was significant improvement in the mean Berg Balance Scale score (P=0.004), Star Excursion Balance Test score (SEBT) (P<0.001 both legs), and Multi Directional Reach Test score (P=0.002). There was no significant change on the Modified Clinical Test for Sensory Integration in Balance. Balance games on the Nintendo "Wii Fit Plus" disc can be used as a tool for balance training in community-dwelling persons 60 years of age and older.


Combatting Social Isolation Among Older Adults in a Time of Physical Distancing: The COVID-19 Social Connectivity Paradox.
Social isolation is an important public health issue that has gained recognition during the COVID-19 pandemic because of the risks posed to older adults based on physical distancing. The primary purposes of this article are to provide an overview of the complex interconnectedness between social isolation, loneliness, and depression while introducing the COVID-19 Connectivity Paradox, a new concept used to describe the conflicting risk/harm continuum resulting from recommended physical distancing. In this context, examples will be provided for practical and feasible community-based models to improve social connectivity during COVID-19 by adjusting the processes and modalities used to deliver programs and services to older adults through the aging social services network. The COVID-19 pandemic has highlighted the need for clinical and community-based organizations to unite and form inter-sectorial partnerships to maintain the provision of services and programs for engaging and supporting older adults during this difficult time of physical distancing and shelter-in-place and stay-at-home orders. The aging social services network provides a vital infrastructure for reaching older underserved and/or marginalized persons across the U.S. to reduce social isolation. Capitalizing on existing practices in the field, older adults can achieve distanced connectivity to mitigate social isolation risk while remaining at safe physical distances from others.


Leak testing. Getting down to the fundamentals of leak detection and measurement.
There are a variety of leak testing techniques in use today. When considering an item requiring leak testing it is important to ascertain first whether detection of the leak or measurement of the leakage rate is more important. Quantifying the leakage rate will dictate the leak measurement technique that is required.


Difficult dementia: six steps to control problem behaviors.
For patients with a confirmed diagnosis of dementia, your challenge is to promote a quality life during their remaining years. This task often includes managing problem behaviors. A systematic approach starts with pinpointing the nature of the specific behavior, reviewing possible physical and emotional stressors, and checking for coexisting affective or psychotic disorders. It often helps to reduce environmental stimulation and to simplify the patient's tasks. Drug therapy with an antipsychotic or benzodiazepine is indicated if a clear-cut behavioral strategy has not proven fully effective, the behavior has been well documented, and the behavior presents a clear danger to the patient or others or prevents necessary care from occurring.


Difference in prognosis between T- and B-cell lymphomas: clinical study at Shikoku Cancer Center Hospital.
In order to determine whether the surface marker phenotypes of non-Hodgkin's lymphomas affect the prognosis, we have studied the differences in response rate and duration of survival between T- and B-cell lymphomas. Sixty-four patients who underwent first-line therapy, including combination chemotherapy and/or radiotherapy, from February 1979 to August 1985 were evaluated. With the aid of standard immunological methods and monoclonal antibodies related to T-cells and B-cells, 21 T-cell lymphomas and 21 B-cell lymphomas were identified. In the other 22 cases phenotypes were not determined mainly because of the inability to obtain fresh samples. The complete remission rate was 100% for B-cell lymphomas and 52.3% for T-cell lymphomas. The median survival time for patients with lymphomas of Stage III and IV, excluding those with low-grade histology, was nine months for T-cell lymphomas and 17 months for B-cell lymphomas. T-cell lymphomas were found to have significantly poorer prognosis than B-cell lymphomas. One patient with B-cell lymphoma and six patients in an undetermined phenotype group, who were treated with combination chemotherapy, have been alive more than three years without relapse and these patients are considered potentially cured. Our results suggest that the surface marker phenotype study of lymphoma cells as well as histological subtyping is important in prognosis and that more effective therapy is needed to improve the prognosis of T-cell lymphomas.


Primary school teachers' attitudes about children with attention deficit/hyperactivity disorder and the role of pharmacological treatment.
Clinical experience and research suggest that teachers' attitudes about attention deficit/hyperactivity disorder (ADHD) are an important factor influencing access to specialist assessment and treatment, including medication. We performed a thematic analysis of comments written by primary school teachers who participated in a case-vignette study investigating the ability of teachers to recognise ADHD. Teachers read one of four types of vignette describing the behaviour of a nine-year-old child who met diagnostic criteria for ADHD (either a boy or a girl with inattentive or combined subtype of ADHD). They answered questions (identical for all types of vignette) about their views regarding the problems and their management. Teachers were invited to add their own comments. Altogether 496 teachers from 110 schools completed the questionnaire: 250 (50%) teachers from 94 schools wrote at least one comment, adding up to 341 comments. Regarding their views on the need to refer the child to specialist services, 32 teachers made comments that reflected caution. The most frequent comments were that it was too early to say whether a referral was necessary, the problems were not severe enough or the main support would come from school. Teachers also reported a lack of knowledge about specialist services or criticised them. When asked whether medication might be beneficial for the child, 125 teachers expressed hesitant or negative views: that it was premature to express an opinion about medication or too soon to give medication to the child; that medication was not necessary or should not be used at all; or that the problems were not severe enough or were emotional in nature. Only five teachers reported having a positive experience of the effect of medication. Teachers' comments suggested a strong preference in using within-school strategies for the management of children with ADHD. Teachers were reluctant to endorse medication for DHD and expressed negative views about its use. Health services should support teachers' management of ADHD-related behaviours in school and provide information to increase teachers' ability to identify the need for a referral to specialist health services.


[A case of successful management of nonresectable pancreas cancer with liver metastasis by intra-arterial infusion chemotherapy with gemcitabine hydrochloride, 5-FU, CDDP and administration of tegafur/uracil].
We report a case of a 43-year-old man with liver metastasis of advanced pancreatic cancer successfully treated with intra-arterial regional chemotherapy. The patient was admitted to our hospital suffering from anorexia and back pain. Abdominal CT showed pancreatic tail cancer with liver and Schnitzler metastasis. We decided a curative operation was impossible. Then, enteric-coated tegafur/uracil (400 mg) was administered. Simultaneously, intraarterial infusion with CDDP, 5-fluorouracil (500 mg) and infusion of gemcitabine (1,000 mg) with 50 microg of AT-II was given once a week. After 3 courses, the pancreatic tumor was reduced and the tumor markers decreased. Multiple metastatic liver tumors remarkably decreased. As a result, the maximum diameter of the pancreatic tumor decreased from 7 cm to 5 cm on the CT-scan. Serum carbohydrate antigen 19-9 (CA19-9) decreased from 122,000 U/ml to 10,200 U/ml. Moreover, the performance status of patient also improved. He was able to receive outpatient treatment despite his terminal cancer. Furthermore, the patient can take sufficient meals without any adverse effects. His quality of life has been preserved. This regimen could well be effective for advanced pancreatic cancer.


Real-time observation of glomerular hemodynamic changes in diabetic rats: effects of insulin and ARB.
The progression of diabetic nephropathy is closely related to disturbances in glomerular hemodynamics, such as glomerular hypertension and/or hyperperfusion. The aim of this study was to observe and to analyze glomerular hemodynamics in rats with diabetes mellitus (DM) in vivo using confocal laser scan microscopy (CLSM). We also examined the effects of candesartan cilexetil (TCV-116), a selective angiotensin II type 1 receptor blocker (ARB), on glomerular hemodynamics in DM. Munich-Wistar rats were divided into six groups: (1) four-day control; (2) four-day DM; (3) 28-day control; (4) 28-day DM; (5) DM treated with insulin; (6) DM treated with TCV-116. The kidney-to-body weight ratio, glomerular volume, and proteinuria were estimated. Glomerular hemodynamic changes were observed using CLSM and renal expression of endothelial nitric oxide synthase (eNOS), and neuronal nitric oxide synthase (nNOS) was evaluated by immunofluorescence. The kidney-to-body weight ratio, glomerular volume, the diameters of afferent arterioles (AA) and efferent arterioles (EA), erythrocyte velocities within glomeruli, and volume flow in glomerular capillary loops in four-day DM were significantly higher than in control rats, and increases were even more pronounced in the 28-day DM. TCV-116 treatment ameliorated all these findings and significantly decreased proteinuria, but there was no effect on the blood glucose level. On the other hand, insulin treatment was followed by normalization of all these changes induced in DM. Enhanced renal expression of eNOS in DM was suppressed when treated with either TCV-116 or insulin, while expression of nNOS was unaltered among the four groups. This imaging procedure allowed us to evaluate glomerular microcirculation in vivo, including the diameters of AA and EA, erythrocyte velocity, and volume flow. DM significantly induced glomerular hemodynamic alteration and renal hypertrophy. DM treated with either insulin or ARB ameliorated these changes. This study shows that progress in imaging technology promises to make major contributions to revealing the involvement of hemodynamic changes in glomerular diseases, aiding prognosis and the monitoring of therapeutic effects, as well.


Interaction of KCNE subunits with the KCNQ1 K+ channel pore.
KCNQ1 alpha subunits form functionally distinct potassium channels by coassembling with KCNE ancillary subunits MinK and MiRP2. MinK-KCNQ1 channels generate the slowly activating, voltage-dependent cardiac IKs current. MiRP2-KCNQ1 channels form a constitutively active current in the colon. The structural basis for these contrasting channel properties, and the mechanisms of alpha subunit modulation by KCNE subunits, are not fully understood. Here, scanning mutagenesis located a tryptophan-tolerant region at positions 338-340 within the KCNQ1 pore-lining S6 domain, suggesting an exposed region possibly amenable to interaction with transmembrane ancillary subunits. This hypothesis was tested using concomitant mutagenesis in KCNQ1 and in the membrane-localized 'activation triplet' regions of MinK and MiRP2 to identify pairs of residues that interact to control KCNQ1 activation. Three pairs of mutations exerted dramatic effects, ablating channel function or either removing or restoring control of KCNQ1 activation. The results place KCNE subunits close to the KCNQ1 pore, indicating interaction of MiRP2-72 with KCNQ1-338; and MinK-59,58 with KCNQ1-339, 340. These data are consistent either with perturbation of the S6 domain by MinK or MiRP2, dissimilar positioning of MinK and MiRP2 within the channel complex, or both. Further, the results suggest specifically that two of the interactions, MiRP2-72/KCNQ1-338 and MinK-58/KCNQ1-340, are required for the contrasting gating effects of MinK and MiRP2.


[Acid-stable and acid-labile interferons inducible by the bovine infectious rhinotracheitis virus].
Attenuated and virulent strains of cattle infectious rhinotracheitis virus (IRTV) induced in cattle leukocytes the production of both acid-stable and acid-labile interferon. The attenuated IRTV strain induced the production of the acid-labile interferon in spleen and bone marrow cells of BALB/C mice. The indication of the assignment of the acid-labile interferon to the leukocyte-type of interferon consists in the activity of bovine interferon in a heterologous culture of human diploid fibroblasts and a higher interferon titer in bone marrow than in spleen cells (bone marrow cells contain B-cells which produce leukocyte interferon).


Financial directions ... the firm's ability to control funds flow.
The primary key to an improvement in financial flexibility for most firms will be through the operating margin. Increases in margins will have a positive effect on most financial indicators. As a target, we suggest a 4 percent margin. You should try to at least make a 4 percent margin to enhance the survivability of your firm.


Efficacy of Modern Light Curing Units in Polymerizing Peripheral Zones in Simulated Large Bulk-fill Resin-composite Fillings.
The variation in micro-hardness (HV) within simulated large cavities (10 × 6 mm) filled in one increment with three bulk-fill resin-based composites (BF-RBC) was assessed by means of a universal hardness device. Modern blue and violet-blue light curing units (LCUs) were applied in three different positions, by rotating the LCU in 120° steps. The exposure distance was 3 mm. One center and two peripheral (4-mm apart from the center) HV line profiles were measured in 0.5-mm steps at 24 hours postpolymerization to calculate the depth of cure (DOC). Incident light, irradiance, and spectral distribution were recorded. A multivariate analysis (general linear model) assessed the effect of the varied parameters as well as their interaction terms on HV and DOC. The effect of LCU rotation was not significant ( p=0.109). The DOC varied between 3.46 mm and 5.50 mm and was more strongly influenced by the BF-RBC ( p<0.001, ηP2=0.774), followed by the width of specimen ( p<0.001, ηP2=0.554), while the influence of the LCU was very low ( p<0.06, ηP2=0.070). Whether a BF-RBC filling is cured as well in the periphery as in the center depends more on the material than on the curing unit used.


Natalizumab: a country-based surveillance program.
Natalizumab is a humanized monoclonal antibody with a selective adhesion-molecule inhibitor effect, and a demonstrated efficacy in decreasing the frequency of relapses and progression of disability in relapsing-remitting multiple sclerosis (RR MS). After the approval of FDA and EMEA in MS cases unresponsive to immunomodulating therapy or in severe MS patients also not previously treated with interferons, and considering the concern on the possible side effects, an accurate program of surveillance was organized in our country by a combined effort of AIFA, Cineca, Department of Pharmacology of University of Bologna, and a group of neurologists appointed by the National Society of Neurology (SIN). After 15 months from the authorization of natalizumab therapy in MS, as of 31 March 2008, 908 cases have been treated with natalizumab and enrolled in this pharmaco-vigilance study. The mean age is 35 years, while the duration of disease is longer and disability is higher than that reported in the registrative study. Side effects are at the moment mild and similar to those previously described. At follow-up, the majority of treated cases are stable or ameliorated. The treatment was discontinued in 6% of patients.


Advanced multimodal diagnostic approaches for detection of lung cancer.
Lung cancer (LC) emerges as a principle cause of death among smokers and is also one of the most lethal forms of cancer in nonsmokers. LC is mainly classified as non-small cell lung cancer (NSCLC), small cell LC, and lung carcinoid tumor. NSCLC is the most prevalent form of LC and its early stage diagnosis is essential to reduce mortality rate of patients and provide specific therapy. The field of LC diagnostics witnessed a gradual escalation with advancement in technology. Areas covered: This comprehensive review focuses on classification of LC and advanced diagnostics for LC detection like biosensors, biomarkers, nanotechnology-based diagnostics, wearable devices, mobile health, artificial intelligence (AI), aptamers, and molecularly imprinted polymers (MIPs). Expert opinion: Liquid biopsy and breath analysis developments are the most promising and advanced technologies for the detection of biomarkers associated with LC. Wearable devices and AI are two niche areas that require development and standardization for commercialization. The upcoming technology based on nanosystems includes robots, fibers, and particles for sensitive detection of LC. In the near future, nanotechnology-based theranostics, aptamers, and MIPs will emerge in early-stage diagnosis of LC.


Identifying influence of perceived quality and satisfaction on the utilization status of the community clinic services; Bangladesh context.
Bangladesh is one among the few countries of the world that provides free medical services at the community level through various public health facilities. It is now evident that, clients' perceived quality of services and their expectations of service standards affect health service utilization to a great extent. The aim of the study was to develop and validate the measures for perception and satisfaction of primary health care quality in Bangladesh context and to identify their aspects on the utilization status of the Community Clinic (CC) services. This mixed method cross sectional survey was conducted from January to June 2012, in the catchment area of 12 Community Clinics (CCs). Since most of the outcome indicators focus mainly on women and children, women having children less than two years of age were randomly assigned and interviewed for the study purpose. Data for the development of perceived service quality and satisfaction tools were collected through Focus Group Discussion (FGD), key informants interview and data for measuring the utilization status were collected by an interviewer administered pretested semi-structured questionnaire. About 95% of the respondents were Muslims and 5% were Hindus. The average age of the respondents was 23.38 (SD ± 4.15) years and almost all of them are home makers. The average monthly expenditure of their family was 7462.92 (SD ± 2545) BDT equivalent to 95 (SD ± 32) US$. To measure lay peoples' perception and satisfaction regarding primary health care service quality two scales e.g. Slim Haddad's 20-item scale for measuring perceived quality of primary health care services (PQPCS) validated in Guinea and Burkina Fuso and primary care satisfaction survey for women (PCSSW) developed by Scholle and colleagues 2004; is a 24-item survey tool validated in Turkey were chosen as a reference tools. Based on those, two psychometric research instruments; 24 items PQPCS scale (chronbach's α =0.89) and 22-items Community Clinic Service Satisfaction (CCSS) scale (chronbach's α = 0.97), were constructed and validated for measuring perceived service quality and satisfaction in Bangladesh context. This study showed mothers with preprimary education [(χ2 = 4.20, p = 0.04), AOR with 95% CI = 1.89 (1.03, 3.53)] utilized the limited curative care services more than educated mothers. On the contrary, higher income families [for income group 5000-10,000 BDT χ2 = 8.83, p = 0.003 and AOR with 95% CI = 0.37(0.19, 0.71)] and [for income group above 10,000 BDT χ2 = 5.02, p = 0.025 and AOR with 95% CI = 0.40 (0.18, 0.89)] and families having cultivable lands [for 5-10 decimal group χ2 = 5.51, p = 0.19, and AOR with 95% CI = 0.56 (0.35, 0.91)] and [for > 10 decimal group χ2 = 6.70, p = 0.010, and AOR with 95% CI = 0.50 (0.29, 0.84)] utilized the limited curative care services less than their poorer and landless counterpart. The same relationship was observed in case of health education and Antenatal Care (ANC) and Postnatal Care (PNC) services. Women who lived in their own residence used health education services more frequently than those who lived in a rental house [χ2 = 24.00, p = 0.000 and AOR with 95% CI = 1.21, (1.12, 1.30)] and they also increasingly used maternal and child health services χ2 = 27.49, p = 0.000 and AOR with 95% CI 1.61, (1.35, 1.93)]. Perceptions concerning skill and competence of the health care provider [χ2 = 16.90, p = 0.000 and AOR with 95% CI = 1.14, (1.07, 1.22)] and satisfaction indicating interpersonal communication and attitude of the care provider [χ2 = 7.07, p = 0.008 AOR with 95% CI = 1.08, (1.02, 1.15)] were found significant predictors for limited curative care service utilization of CC. Perception related to the quality of management, administration, physical environment of the service point and satisfaction addressing health promotion and women health issues also played significant role on CC's services utilization. Besides parental education and income, client's perception and satisfaction played significant role in CC service utilization. Provider's perception of service quality should be studied. The study findings will enable policy-makers .to improve quality of primary health care services, realizing providers' and patients' ideas of CC service quality.


The Rhodobacter sphaeroides ECF sigma factor, sigma(E), and the target promoters cycA P3 and rpoE P1.
Rhodobacter sphaeroides rpoE encodes a 19.2 kDa protein, sigma(E), related to members of the extra-cytoplasmic function subfamily of eubacterial RNA polymerase sigma factors. We demonstrate that sigma(E) directs transcription from rpoE P1, the promoter for the rpoEchrR operon, and from cycA P3, a promoter for the cytochrome c2 structural gene. Comparison of these sigma(E)-dependent promoters reveals significant sequence conservation in their -35 and -10 regions; however, rpoE P1 is over 80-fold stronger than cycA P3. Both promoters contain identical -35 hexamers, (-36)TGATCC(-31), that appear to constitute the preferred sequence, since any single base mutation in this region of cycA P3 reduces promoter function. The higher activity of rpoE P1 appears to reflect a better -10 region, (-13)TAAGA(-9), as it contains four out of five of the nucleotides found to be important to sigma(E)-dependent transcription. We also propose that ChrR acts as an inhibitor of sigma(E), since these two proteins can form a complex, and DeltachrR mutations increase sigma(E)-dependent transcription. ChrR is believed to respond to a signal from tetrapyrrole biosynthesis because loss of function mutations in chrR lead to cohemin resistance. Based on our observations, we present a model in which cohemin resistance is conferred by increasing sigma(E) activity.


Older peoples' views on cardiovascular disease medication: a qualitative study.
There is increasing evidence for the potential benefits and harms of cardiovascular disease (CVD) medications in older people (>75 years) prompting updating of clinical guidelines. We explored the views of older people about CVD medication to inform guideline development. Qualitative study using semistructured interviews and focus groups. An ethnically diverse group of community dwelling older people were purposefully recruited from northern New Zealand using flyers in primary care clinics, local libraries, social groups, and places of worship, and by word of mouth. Interviews and focus groups were digitally recorded, transcribed verbatim, and analysed using an iterative and inductive approach to thematic analysis. Thirty-nine participants from 4 ethnic groups were recruited (mean 74 years; range 61-91 years; Māori (7), South Asian (8), European (9), and Pasifika (15)). Most participants were taking CVD medication/s. Four main themes emerged: (i) emphasizing the benefits of CVD medication and downplaying the harms; (ii) feeling compelled to take medication; (iii) trusting "my" doctor; and (iv) expecting medication to be continued. Findings raise questions about older people's agency in decision-making regarding CVD medication. CVD risk management guidelines for older people could include strategies to support effective communication of the potential benefits and harms of CVD medication in older people, balancing life expectancy, and the expected duration of therapy.


Stability of car following with human memory effects and automatic headway compensation.
This paper addresses the study of some appropriate control strategies in order to guarantee the exponential stability of a class of deterministic microscopic car-following models including human drivers' memory effects and automated headway controllers. More precisely, the delayed action/decision of human drivers is represented using distributed delays with a gap and the considered automated controller is of proportional derivative type. The analysis is performed in both delay parameter and controller gain parameter spaces, and appropriate algorithms are proposed. Surprisingly, large delays and/or gains improve stability for the corresponding closed-loop schemes. Finally, some illustrative examples as well as various interpretations of the results complete the presentation.


Coordinate late expression of trefoil peptide genes (pS2/TFF1 and ITF/TFF3) in human breast, colon, and gastric tumor cells exposed to X-rays.
The trefoil factors (TFFs) are pleiotropic factors involved in organization and homeostasis of the gastrointestinal tract, estrogen responsiveness, inflammatory disorders, and carcinogenesis. In an earlier study using cDNA array technologies to identify new genes expressed in irradiated cell survivors, we isolated a cDNA clone corresponding to the reported human TFF1 gene (E. K. Balcer-Kubiczek et al., Int. J. Radiat. Biol., 75: 529-541, 1999). To determine whether expression of other TFFs is altered by ionizing radiation, we quantified changes in expression of TFF3 as well as TFF1 in RNA samples obtained from irradiated and control human tumor breast, colon, and gastric tumor cells and examined expression kinetics up to 2 weeks after irradiation. X-ray-induced TFF1 and TFF3 expression profiles were compared with those induced by hydrogen peroxide (H2O2) or 17beta-estradiol (ES). The results revealed that TFF1 and TFF3 mRNA are coinduced by X-irradiation in a subset of the lines, but substantial heterogeneity in their responses was observed in cells derived from a single cell type. TFF1 and TFF3 transcriptional response to X-irradiation differed from that to H2O2 or ES in the timing of their induction as well as tissue-type dependence, i.e., their induction pattern after X-irradiation was late and sustained, whereas their induction by H2O2 or ES was early and transient. TFF1 mRNA, protein production in the cytoplasm, and secretion in the culture supernatant were coordinately regulated after X-irradiation. There was no requirement for TP53 in this induction. These results demonstrate the existence of a novel class of radiation-responsive genes that might be involved in bystander effects.


Facile and Economic Synthesis of Robust Non-Nucleophilic Electrolyte for High-Performance Rechargeable Magnesium Batteries.
A cost-effective and highly efficient electrolyte with a wide electrochemical window, high reversibility of Mg plating/stripping, non-/low-corrosivity, good compatibility with cathode materials, and tolerance of trace water and impurity is crucial for the commercialization of rechargeable magnesium batteries. In this work, a novel boron-centered non-nucleophilic electrolyte that meets all the above requirements is prepared via a facile and economic approach from the raw materials B(TFE)3/MgCl2/CrCl3/Mg (BMCM). The as-prepared BMCM electrolyte is mainly composed of tetracoordinated anions [B(TFE)4]- and solvated cations [Mg2(μ-Cl)2(DME)4]2+. The BMCM electrolyte demonstrates attractive electrochemical performance, with a low overpotential (∼139 mV), a high Coulombic efficiency (∼97%), a high anodic stability (∼3.5 V vs Mg/Mg2+), and a long-term (more than 500 h) cycling stability. Moreover, BMCM shows good compatibility with the CuS cathode material. The CuS|BMCM|Mg full cell delivers a discharge specific capacity of 231 mAh g-1 (at 56 mA g-1), which can retain ∼88% even after 100 cycles. Importantly, the BMCM electrolyte is cost-effective and tolerant of trace impurity and water, which has great potential to be commercialized. This work is expected to promote the development of practical rechargeable magnesium batteries.


Modeling for gellan gum production by Sphingomonas paucimobilis ATCC 31461 in a simplified medium.
Gellan gum production was carried out by Sphingomonas paucimobilis ATCC 31461 in a simplified medium with a short incubation time, and a kinetic model for understanding, controlling, and optimizing the fermentation process was proposed. The results revealed that glucose was the best carbon source and that the optimal concentration was 30 g liter(-1). As for the fermenting parameters, considerably large amounts of gellan gum were yielded by an 8-h-old culture and a 4% inoculum at 200 rpm on a rotary shaker. Under the optimized conditions, the maximum level of gellan gum (14.75 g liter(-1)) and the highest conversion efficiency (49.17%) were obtained in a 30-liter fermentor in batch fermentation. Logistic and Luedeking-Piret models were confirmed to provide a good description of gellan gum fermentation, which gave some support for the study of gellan gum fermentation kinetics. Additionally, this study is the first demonstration that gellan gum production is largely growth associated by analysis of kinetics in its batch fermentation process. Based on model prediction, higher gellan gum production (17.71 g liter(-1)) and higher conversion efficiency (57.12%) were obtained in fed-batch fermentation at the same total glucose concentration (30 g liter(-1)).


Calcitonin promotes mouse pre-implantation development: involvement of calcium mobilization and P38 mitogen-activated protein kinase activation.
The study was designed to examine the effects of calcitonin (CT) on the development of murine pre-implantation embryos and possible molecular mechanisms involved in the process. In the present study, the 2-cell embryos were treated with different concentration of CT in vitro for the indicated time and the results demonstrated that CT promoted the development of the pre-implantation embryos in a dosage-dependent manner by increasing the intracellular Ca(2+) level. Furthermore, the present study showed that CT significantly increased the expression of phospho-P38MAPK (Mitogen-Activated Protein Kinase) of the pre-implantation embryos by Western blots and pre-treatment of specific P38MAPK inhibitor significantly reduced the promotion effects of CT on the embryonic development in vitro culture. Moreover, the results of intrauterine horn injection showed that the average number of embryos implanted in CT-antibody or specific P38 MAPK inhibitor-treated uterus was significantly lower than that of the corresponding control, respectively. And the observation of tissue specimen suggested that some embryos were degenerated in CT-antibody or specific P38 MAPK inhibitor-treated uterus, and adipose vacuoles were present in the decidual cells. In conclusion, CT promoted the development of pre-implantation embryos and the intracellular Ca(2+) -dependent P38MAPK signal molecule was involved in the process.