Altered baroreflex sensitivity in young women with a family history of hypertension.
A positive family history of hypertension (+FH) is a risk factor for the future development of hypertension. Hypertension is associated with reductions in baroreflex sensitivity (BRS). Therefore, we hypothesized that young women with a +FH [ n = 12, 22 ± 1 yr, body mass index (BMI) 21 ± 1 kg/m2, mean arterial pressure (MAP) 79 ± 1 mmHg] would have lower BRS compared with young women without a family history of hypertension (-FH) ( n = 13, 22 ± 1 yr, BMI 21 ± 1 kg/m2, MAP 77 ± 2 mmHg, all P > 0.05 between groups). Continuous measurements of muscle sympathetic nerve activity, blood pressure, and electrocardiogram derived R-R interval were recorded at rest and during a Valsalva maneuver. Both cardiovagal BRS and vascular sympathetic BRS were assessed. Resting cardiovagal BRS was reduced in the +FH women (all sequences: -FH 32.3 ± 3.7 vs. +FH 20.2 ± 2.9 ms/mmHg, P = 0.02). Cardiovagal BRS during phase IV (-FH 16.5 ± 2.7 vs. +FH 7.6 ± 1.3 ms/mmHg, P < 0.01) but not phase II (-FH 5.5 ± 0.9 vs. +FH 5.0 ± 0.8 ms/mmHg, P = 0.67) of the Valsalva maneuver was also lower in the +FH women. Vascular sympathetic BRS at rest (-FH -2.38 ± 0.7 vs. +FH -2.33 ± 0.3 bursts· min-1·mmHg-1, P = 0.58) and during the Valsalva (-FH -0.74 ± 0.23 vs. +FH -0.66 ± 0.18 bursts·15 s-1·mmHg-1, P = 0.79) were not different between groups. These data suggest that healthy young women with a positive family history of hypertension have reduced cardiovagal BRS. This may be one mechanism contributing to the increased incidence of hypertension in this population later in life. NEW & NOTEWORTHY Having a family history of hypertension increases the risk of developing future hypertension. Reductions in baroreflex function have been demonstrated in hypertension and are an important marker for future cardiovascular disease. We show that young women with a family history of hypertension have lower cardiovagal baroreflex sensitivity. This alteration in autonomic function may be one mechanism contributing to the future incidence of hypertension in this patient population.


Mechanical Stimulation on Mesenchymal Stem Cells and Surrounding Microenvironments in Bone Regeneration: Regulations and Applications.
Treatment of bone defects remains a challenge in the clinic. Artificial bone grafts are the most promising alternative to autologous bone grafting. However, one of the limiting factors of artificial bone grafts is the limited means of regulating stem cell differentiation during bone regeneration. As a weight-bearing organ, bone is in a continuous mechanical environment. External mechanical force, a type of biophysical stimulation, plays an essential role in bone regeneration. It is generally accepted that osteocytes are mechanosensitive cells in bone. However, recent studies have shown that mesenchymal stem cells (MSCs) can also respond to mechanical signals. This article reviews the mechanotransduction mechanisms of MSCs, the regulation of mechanical stimulation on microenvironments surrounding MSCs by modulating the immune response, angiogenesis and osteogenesis, and the application of mechanical stimulation of MSCs in bone regeneration. The review provides a deep and extensive understanding of mechanical stimulation mechanisms, and prospects feasible designs of biomaterials for bone regeneration and the potential clinical applications of mechanical stimulation.


The chemistry of an insect ear: ionic composition of a liquid-filled ear and haemolymphs of Neotropical katydids.
The purpose of this study is to examine and to compare the ionic composition of the haemolymph and the ear fluid of seven species of katydids (Orthoptera: Tettigoniidae) with the aim of providing from a biochemical perspective a preliminary assessment for an insect liquid contained in the auditory organ of katydids with a hearing mechanism reminiscent of that found in vertebrates. A multi-element trace analysis by inductively coupled plasma optical-emission spectrometry was run for 16 elements for the ear liquid of seven species and the haemolymph of six of them. Based on the obtained results, it can be recognized that the ionic composition is variable among the studied insects, but sodium (Na+), potassium (K+), calcium (Ca2+) and magnesium (Mg2+) are the most prominent of the dissolved inorganic cations. However, the ion concentrations between the two fluids are considerably different and the absence or low concentration of Ca2+ is a noticeable feature in the inner ear liquid. A potential relationship between the male courtship song peak frequency and the total ion (Na+, K+, Mg2+ and Ca2+) concentration of the inner ear liquid is also reported.


Age-related differences in performance of phonemic verbal fluency measured by Controlled Oral Word Association Task (COWAT): a meta-analytic study.
Meta-analytical procedures were used to examine the research findings on age-related changes in phonemic verbal fluency measured by the Controlled Oral Word Association Task (COWAT). Data from 26 studies comparing adults from different age ranges were analyzed. An effect of aging was found in almost all age comparisons especially after 40 years of age. Results revealed a decline of this verbal ability after 60 years, which accelerates through the late 80s. Gender may influence COWAT performance after the sixth decade, favoring women over men. These results may be important in clinical situations where COWAT is used to assert pathological changes.


Frequency of low carnitine levels in children on dialysis.
To determine the frequency of low carnitine levels, we measured serum carnitine in pediatric patients on peritoneal dialysis (PD) and hemodialysis (HD). Our prospective cross-sectional study was conducted from September 2004 to March 2005 in a single pediatric center, and included patients under 17 years of age who had been on HD or PD for more than 3 months. Patients with primary carnitine deficiency were excluded. A 4-day food diary was used for carnitine intake quantification. Serum total and free carnitine and acylcarnitine were measured. We compared patients with low and normal carnitine levels using the chi-square test, Mann-Whitney U-test, and Spearman correlation. Of 100 study patients, 70 were on PD, and 61 were male. The median age was 13 years, and the median time on dialysis, 10.5 months. Median serum free carnitine was 32.75 nmol/mL. Carnitine levels were lower than normal in 75 patients and reached the level of deficiency in 29. No difference was found between the dialysis modality types for any fraction of carnitine. No correlation was found between the level of free carnitine and time on dialysis (r = -0.009, p = 0.9) or carnitine intake (r = -0.84, p = 0.4). In conclusion, the frequency ofl ow serum carnitine among pediatric patient on dialysis is high.


Enantiodivergent Synthesis of Tertiary α-Aryl 1-Indanones: Evidence Toward Disparate Mechanisms in the Palladium-Catalyzed Decarboxylative Asymmetric Protonation.
Herein, we describe a study into the scope and origin of an enantiodivergent effect in the palladium-catalyzed decarboxylative asymmetric protonation. By switching the achiral proton source, both enantiomers of a series of tertiary α-aryl-1-indanones are readily accessed from the corresponding α-aryl-β-keto allyl esters. In this example of dual stereocontrol, enantioselectivities up to 94% (S) and 92% (R) were achieved using Meldrum's acid and formic acid, respectively. In an attempt to rationalize this switch in absolute configuration an investigation of the ambiguous mechanism of the decarboxylative asymmetric protonation was conducted. A novel catalytic cycle for the reaction with formic acid is proposed and subjected to a variety of experimental studies.


Enhanced Fluorescence ELISA Based on HAT Triggering Fluorescence "Turn-on" with Enzyme-Antibody Dual Labeled AuNP Probes for Ultrasensitive Detection of AFP and HBsAg.
At present, enzyme-linked immunosorbent assay (ELISA) is considered to be the most appropriate approach in clinical biomarker detection, with good specificity, low cost, and straightforward readout. However, unsatisfactory sensitivity severely hampers its wide application in clinical diagnosis. Herein, we designed a new kind of enhanced fluorescence enzyme-linked immunosorbent assay (FELISA) based on the human alpha-thrombin (HAT) triggering fluorescence "turn-on" signals. In this system, detection antibodies (Ab2) and HAT were labeled on the gold nanoparticles (AuNPs) to form the detection probes, and a bisamide derivative of Rhodamine110 with fluorescence quenched served as the substrate of HAT. After the sandwich immunoreaction, HAT on the sandwich structure could catalyze the cleavage of the fluorescence-quenched substrate, leading to a strong fluorescence signal for sensing ultralow levels of alpha fetoprotein (AFP) and hepatitis B virus surface antigen (HBsAg). Under the optimized reaction conditions, AFP and HBsAg were detected at the ultralow concentrations of 10-8 ng mL-1 and 5 × 10-4 IU mL-1, respectively, which were at least 104 times lower than those of the conventional fluorescence assay and 106 times lower than those of the conventional ELISA. In addition, we further discussed the efficiency of the sensitive FELISA in clinical serum samples, showing great potential in practical applications.


Effects of graded renal artery constriction on blood pressure, renal artery pressure, and plasma renin activity in Goldblatt hypertension.
One-kidney, one clip (1K1C) and two-kidney, one clip (2K1C) Goldblatt hypertension was produced in rats by placing 0.30, 0.25, or 0.20 mm silver clips on the left renal artery. Mean arterial pressure (MAP) and plasma renin activity (PRA) were measured in conscious rats 24 to 28 days after clipping. The MAP in control rats (n = 38) was 116 +/- 1 mm Hg (mean +/- SEM). The 0.30, 0.25, and 0.20 mm clips produced MAPs of 133 +/- 2, 161 +/- 5, and 189 +/- 5 mm Hg, respectively, in 1K1C rats, and 123 +/- 2, 129 +/- 3, and 172 +/- 5 mm Hg in 2K1C rats (n = 17-20). When 1K1C and 2K1C groups were compared, MAP was significantly greater in 1K1C rats at all clip sizes. No treatment group's PRA was different than control (4.8 +/- 0.4 ng AI/ml/hr), except for the 0.20 mm 2K1C rats (16.2 +/- 3.1 ng AI/ml/hr). Renal artery pressure (RAP) was measured in another series of experiments and was not different from control in all but the 0.20 mm 1K1C rats. With identical clip sizes, 2K1C rats showed smaller pressure gradients than 1K1C across the clips: 0.30 mm, 8.5 +/- 1.7 vs 10.7 +/- 1.9 mm Hg; 0.25 mm, 16.5 +/- 1.2 vs 42.1 +/- 7.5 mm Hg; 0.20 mm, 51 +/- 5.3 vs 79.1 +/- 5.7 mm Hg (n = 8-12). Therefore, both the increase in MAP and the pressure gradient across the clip were greater in the 1K1C rats at every clip size.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of vitamin D-related gene polymorphisms on attempted suicide.
Emerging evidence suggests that vitamin D might protect from attempted suicide. The study aimed to investigate the associations between single-nucleotide polymorphisms (SNPs) related to vitamin D levels identified in a large genome-wide association study and attempted suicide in rural China. This 1:1 matched case-control study included altogether 510 suicide attempters and 510 community controls. Genotypes of four target SNPs (DHCR7-rs12785878, CYP2R1-rs10741657, GC-rs2282679, and CYP24A1-rs6013897) were determined, and a genetic risk score (GRS) was constructed to evaluate the combined effect of them. Demographic and psychological information was acquired through face-to-face interviews. The A allele of CYP24A1-rs6013897 was significantly associated with attempted suicide (OR = 1.27, 95% CI, 1.03-1.58, P = 0.029), even after adjusting for demographic and psychological confounders (adjusted OR = 1.53, 95% CI, 1.01-2.30, P = 0.043). The GRS analyses revealed a significantly higher risk of attempted suicide with a greater number of low vitamin D alleles (adjusted OR = 1.33, 95% CI, 1.13-1.58, P < 0.001). Subgroup analyses stratified by sex indicated that the genetic associations were only significant among males with adjusted ORs of 3.77 (95% CI, 1.56-9.10) for the A allele of rs6013897 and 2.04 (95% CI, 1.32-3.17) for GRS. Our findings identity CYP24A1-rs6013897 as a potential biomarker for attempted suicide and indicate that a genetic predisposition to lower vitamin D levels may contribute to attempted suicide. It suggests the possibility that vitamin D may have the preventive potential for attempted suicide.


Inhibitory effects of benzoate on chiral inversion and clearance of N(G)-nitro-arginine in conscious rats.
N(G)-nitro-arginine (NNA) is known to exhibit stereoselective pharmacokinetics in which N(G)-nitro-d-arginine (d-NNA) has a faster clearance rate than N(G)-nitro-l-arginine (l-NNA) in anesthetized rats, and d-NNA undergoes unidirectional chiral inversion. It was postulated that chiral inversion of d-NNA was performed in a two-step pathway by d-amino acid oxidase (DAAO) followed by an unidentified transaminase. Such chiral inversion contributes (at least partially) to the pharmacokinetic stereoselectivity of NNA. This study used the selective inhibitor of DAAO, sodium benzoate, to test the above hypothesis. An i.v. bolus injection of d-NNA (32 mg/kg) and l-NNA (16 mg/kg) in conscious rats exhibited biphasic disposition with different pharmacokinetic parameters in a stereospecific manner (approximately 5-10-fold differences). Unidirectional chiral inversion of d-NNA but not l-NNA was found from these animals. In addition to its similar inhibitory effects on the d-NNA conversion and DAAO activity in kidney homogenates, sodium benzoate completely blocked chiral inversion of d-NNA and led to a smaller stereospecific difference, reflected by a nearly 50% reduction of d-NNA clearance and a 2-fold increase in t(1/2) and area under the curve of d-NNA in benzoate-pretreated rats. The results suggest that DAAO plays an essential role in chiral inversion of d-NNA and chiral inversion contributes mostly to the pharmacokinetic stereospecificity of NNA.


ABCE1, a member of ATP-binding cassette transporter gene, encodes peptides capable of inducing HLA-A2-restricted and tumor-reactive cytotoxic T lymphocytes in colon cancer patients.
To provide a scientific basis for specific immunotherapy of colon cancer, this study focused on the identification of tumor-associated antigens recognized by HLA-A2-restricted and cancer-reactive cytotoxic T lymphocytes (CTLs) from tumor-infiltrating lymphocytes (TIL) of a colon cancer patient. We identified a gene coding a member of the ATP-binding cassette transporter (ABCE1), which is known as an inhibitor to the 2-5A/RNase L system, a central pathway of interferon action, and its gene expression is amplified in drug-resistant cells. The ABCE1 mRNA was ubiquitously expressed in tumor cell lines, as well as normal cells or tissues. Among 21 peptides with the HLA-A2 binding motifs, 2 ABCE1-derived peptides were recognized by the colon cancer-reactive CTLs in a dose-dependent manner. CTL precursors reactive to these 2 ABCE1 peptides were detected in the peripheral blood mononuclear cells (PBMCs) of the colon cancer patient, from whom the TILs had been obtained. In addition, these ABCE1 peptides had the potential to generate HLA-A2-restricted and colon cancer-reactive CTLs from the PBMCs of colon cancer patients, but not from those of healthy donors. Their cytotoxicity against colon cancer was mainly ascribed to peptide-specific and CD8+ CTLs. No definite cytotoxicity was observed against normal T cell blasts, irrespective of the expression of the ABCE1 mRNA. These results indicate that the ABCE1 and its peptides could be target molecules in specific immunotherapy for HLA-A2(+) colon cancer patients.


β2-Microglobulin is an appropriate reference gene for RT-PCR-based gene expression analysis of hematopoietic stem cells.
Real-time reverse transcription polymerase chain reaction (RT-PCR) is regarded as one of the most useful and powerful tools for characterizing hematopoietic stem cells (HSCs), because samples of extremely small cell numbers can be analyzed. The expression levels determined by RT-PCR are based on relative quantification; therefore, the selection of an appropriate reference gene with a relatively stable expression level under most conditions is crucial. Here, we determined that beta2-microglobulin (B2m) is an appropriate reference gene for analyzing mouse HSCs by a novel method using single-cell RT-PCR. Clonally sorted HSCs were subjected to RT reactions with exogenous RNA fragments and then to real-time PCR. Next, the relative gene expression levels of 4 well-known housekeeping genes were quantified in each single cell sample based on the threshold cycle of exogenous RNA. The analysis revealed that B2m expression was reproducibly detected in almost all HSCs and that B2m had the most stable expression level among the compared genes, even after the cells had been cultured under various conditions. Thus, our results indicate that B2m can reliably be used as a reference gene for the relative quantification of expression levels in HSCs across various conditions. Furthermore, our work proposes a novel method for the selection of appropriate reference genes.


Erosion rates near rome, Italy.
Before man's intensive use of the land the rates of erosion near Rome, Italy, were approximately 2 to 3 centimeters per thousand years. With intensive occupation by man the rates have increased by an order of magnitude.


Detection of Entamoeba histolytica antigens in stool in amebiasis.
Stool microscopy, the conventional method of diagnosing intestinal amebiasis, fails to detect Entamoeba histolytica in more than 30-40% of clinically suspected cases. Demonstration of parasite products in clinical specimens has been suggested as an alternative. However, the usefulness of demonstrating amebic antigen in the stools of clinical cases needs to be assessed. A double-antibody sandwich enzyme linked immunosorbent assay (ELISA) using anti-trophozoite antibodies to capture E histolytica specific coproantigen(s) was carried out on stools obtained from 31 patients with microscopically confirmed non-dysenteric amebic colitis, 18 patients with intestinal parasites other than E histolytica and 41 apparently healthy subjects. The assay detected E histolytica specific coproantigen(s) in stools of 23 (74.2%) of 31 subjects with non-dysenteric amebic colitis, none of 18 with other parasitic infections and 1 (2.4%) of 41 apparently healthy subjects. Our results provide evidence for the presence of E histolytica specific coproantigen(s) in stool eluates from patients with amebic infection; this finding can be exploited for confirming ongoing amebic infection. However, the sensitivity of the assay needs to be improved by the use of relevant monospecific/monoclonal antibodies.


Psoriasis as a human model of disease to study inflammatory atherogenesis.
Inflammation is known to play a significant role in the process of atherogenesis and cardiovascular disease (CVD). Indeed, patients with chronic inflammatory diseases are at increased risk for cardiovascular events. However, the mechanisms linking chronic inflammation and CVD remain poorly understood. Psoriasis, a chronic inflammatory skin disease associated with a greater risk of early cardiovascular events, provides a suitable human model to study the pathophysiology of inflammatory atherogenesis in humans. Additionally, cytokines such as TNF-α, IL-17A, and other immune pathways are the common links between the pathogenesis of psoriasis and atherosclerosis, and hence the approved treatments for psoriasis, which include selective cytokine inhibition (e.g., anti-TNF, anti-IL-17A, and anti-IL-12/23) and immune modulation (e.g., methotrexate or cyclosporine), provide an opportunity to examine the effect of modulating these pathways on atherogenesis. We have been using this human model in a large, prospective cohort study, and this review summarizes our approach and results of using this human model to study inflammatory atherogenesis. Specifically, we review simultaneous multimodal imaging of several vascular beds using 18fludeoxyglucose positron emission tomography/computed tomography, 18fludeoxyglucose positron emission tomography/MRI, and coronary computed tomography angiography as well as cardiovascular biomarkers to better understand how modulation of inflammation may impact vascular diseases.


Vicarious pain responders and emotion: Evidence for distress rather than mimicry.
Up to a third of the population experiences pain when seeing another in pain. The mechanisms underlying such vicarious sensory experiences are thought to reflect hyperactive mirror systems (threshold theory) or dysfunctional processing and representation of oneself versus others (self/other theory). This study investigated whether the tendency to experience vicarious pain corresponds to disinhibited physiological reactivity toward other's emotions, and/or greater empathic mimicry of other's physiological state (respiratory behavior) during fear, pain, and positive emotion. Fifty healthy individuals aged 18-55 years (23 vicarious pain responders) completed empathy- and anxiety-related questionnaires, and a film task. Respiration was measured noninvasively with piezoelectric respiration belts while participants viewed emotional film clips depicting three emotions (fear/pain/positive) interspersed with neutral clips. The emotional stimuli depicted scenes in which the characters showed increases or decreases in respiration. The results suggest that vicarious pain responders do not mimic emotional respiratory behavior. Rather, vicarious pain responders had a significantly slower respiration rate for all emotional stimuli (MDiff = 1.40 respiratory cycles, SE = .68), compared to nonresponders. However, this was associated with heightened trait anxiety. The findings suggest vicarious pain is associated with acute distress, rather than empathic mimicry of the emotional states of another.


Polystyrene sulphonates and aspiration pneumonia: a histochemical study.
The histochemical characteristics of a sulphonated polystyrene resin were investigated and compared with those of sulphonic acid residues derived from intrinsic tissue components. The major features of the resin particles were their direct Schiff positivity and basophilia. Unlike the tissue sulphonic acids, the resin particles failed to stain with alcian blue. Because of their acid nature, the particles may be responsible for the onset of an aspiration pneumonia if they are accidentally inhaled by debilitated patients.


Infrared thermography in the detection of brown adipose tissue in humans.
PET-CT using (18)F-FDG is employed for detecting brown adipose tissue (BAT) in humans. Alternative methods are needed because of the radiation and cost of PET-CT imaging. The aim was to evaluate the accuracy of infrared thermography (IRT) in detecting human BAT benchmarked to PET-CT imaging. Seventeen individuals underwent a total of 29 PET-CT scans, 12 of whom were studied twice, after 2 h of cold stimulation at 19°C, in parallel with measurement of skin temperatures overlying the supraclavicular (SCV) fossa and the lateral upper chest (control), before and after cold stimulation. Of the 29 scans, 20 were BAT positive after cold stimulation. The mean left SCV temperature tended to be higher in the BAT-positive group before and during cooling. It was significantly higher (P = 0.04) than the temperature of the control area, which fell significantly during cooling in the BAT-positive (-1.2 ± 0.3°C, P = 0.002) but not in the negative (-0.2 ± 0.4°C) group. The temperature difference (Δtemp) between left SCV and chest increased during cooling in the BAT-positive (1.2 ± 0.2 to 2.0 ± 0.3°C, P < 0.002) but not in the negative group (0.6 ± 0.1 to 0.7 ± 0.1°C). A Δtemp of 0.9°C conferred a positive predictive value of 85% for SCV BAT, superior to that of SCV temperature. The findings were similar on the right. In conclusion, the Δtemp is significantly and consistently greater in BAT-positive subjects. The Δtemp quantified by IRT after 2-h cooling shows promise as a noninvasive convenient technique for studying SCV BAT function.


Dimeric 1,4-benzoquinone Derivatives with Cytotoxic Activities from the Marine-Derived Fungus Penicillium sp. L129.
Two new dimeric 1,4-benzoquinone derivatives, peniquinone A (1) and peniquinone B (2), a new dibenzofuran penizofuran A (3), and a new pyrazinoquinazoline derivative quinadoline D (4), together with 13 known compounds (5-17), were isolated from a marine-derived fungus Penicillium sp. L129. Their structures, including absolute configurations, were elucidated by extensive spectroscopic data and electronic circular dichroism calculations. Compound 1 exhibited cytotoxicity against the MCF-7, U87 and PC3 cell lines with IC50 values of 12.39 µM, 9.01 µM and 14.59 µM, respectively, while compound 2 displayed relatively weak cytotoxicity activities against MCF-7, U87 and PC3 cell lines with IC50 values of 25.32 µM, 13.45 µM and 19.93 µM, respectively. Furthermore, compound 2 showed weak quorum sensing inhibitory activity against Chromobacterium violaceum CV026 with an MIC value of 20 μg/well.


Uses of the electrical skin resistance method in the study of patients with neck and upper extremity pain.
Use of the electrical skin resistance method for the study of neck and upper extremity pain is reported. Skin resistance was mapped for 20 patients who had neck or upper extremity pain without clinical or radiographic evidence of spinal cord or nerve root irritation, but who did present evidence of an abnormality within a cervical intervertebral disc or involving a facet joint of the cervical spine. In general, areas of low skin resistance (sympathetic hyperactivity) corresponded well to areas of subjective pain. The skin resistance pattern has not led to localization of the level of abnormality within the cervical spine, but has been of value in confirming the clinical impression that a pain-producing mechanical or degenerative lesion is present. The test thus adds objective evidence in an area often fraught with subjectivity.


Tilted hexagonal post arrays: DNA electrophoresis in anisotropic media.
Using Brownian dynamics simulations, we show that DNA electrophoresis in a hexagonal array of micron-sized posts changes qualitatively when the applied electric field vector is not coincident with the lattice vectors of the array. DNA electrophoresis in such "tilted" post arrays is superior to the standard "un-tilted" approach; while the time required to achieve a resolution of unity in a tilted post array is similar to an un-tilted array at a low-electric field strengths, this time (i) decreases exponentially with electric field strength in a tilted array and (ii) increases exponentially with electric field strength in an un-tilted array. Although the DNA dynamics in a post array are complicated, the electrophoretic mobility results indicate that the "free path," i.e. the average distance of ballistic trajectories of point-sized particles launched from random positions in the unit cell until they intersect the next post, is a useful proxy for the detailed DNA trajectories. The analysis of the free path reveals a fundamental connection between anisotropy of the medium and DNA transport therein that goes beyond simply improving the separation device.


Nutritional support during pregnancy and lactation.
Needs for virtually all nutrients increase during pregnancy and lactation but those for iron are the most difficult to meet from a normal diet. During pregnancy, nutritional objectives include helping the woman to increase the quality of her diet in protective nutrients as well as energy to meet the elevated needs of gestation, ensuring satisfactory weight gain patterns, prescribing iron and possible folic acid supplements, ensuring that intakes of alcohol, drugs, and other potentially harmful substances are moderate, preparing her for feeding the infant, and coping with any special diet-related problems that may arise. These issues and the management of edema, high blood pressure, and diabetes mellitus are discussed. Prenatal preparations for lactation and diet during lactation are also discussed. Specific objectives of nutritional education on lactation include helping the mother to make the decision to breast or bottle feed, taking steps to prepare her nipples if this is necessary and planning her diet. Dietary adjustments are discussed and a food guide presented. Iron supplements for ther lactating mother and iron, vitamin D, and fluoride supplements for the infant are recommended.


Effect of H2-receptor antagonist pretreatment on vecuronium- and atracurium-induced neuromuscular block.
Seventy-two patients were studied in a double-blind randomized controlled design to assess the effects of oral administration of cimetidine 400 mg, ranitidine 150 mg or placebo 90 min before anaesthesia on the neuromuscular blocking effects of atracurium 0.45 mg kg-1 or vecuronium 0.08 mg kg-1. The times to reappearance of T1 (first response in the train-of-four stimulation) and its recovery to 25% of control were 22.5 (SD) 5.2 and 30 (7.1) min, 30 (10) and 43 (15.4) min, and 25.8 (4.1) and 34 (6.2) min, respectively in the vecuronium groups pretreated with placebo, cimetidine and ranitidine, the times following cimetidine pretreatment being prolonged significantly (P less than 0.05). The respective recovery indices (times for 25-75% recovery of T1) in these three groups were 11.0 (3.5), 17.4 (6.8) and 13.0 (3.9) min. There were no significant differences in any of the variables following ranitidine pretreatment and either neuromuscular blocker or following cimetidine pretreatment and atracurium.


Development of microsatellite loci for the endangered seagrass Zostera japonica (Zosteraceae).
New microsatellite markers were developed for the Asian endangered seagrass Zostera japonica (Zosteraceae) to assess genetic diversity and population structure of this species. In China, Z. japonica populations have drastically decreased since the 1970s. A total of 12 polymorphic tetranucleotide microsatellite loci were isolated and characterized in Z. japonica. The number of alleles per locus ranged from one to 11. The expected and observed heterozygosity ranged from 0 to 0.772 and from 0 to 1.000, respectively. The new microsatellites will be useful in evaluating clonality and population structure of Z. japonica and aiding in conservation and management of the endangered seagrass in Asia.


Combining molecular dynamics and ab initio quantum-chemistry to describe electron transfer reactions in electrochemical environments.
A theoretical model is presented aimed to provide a detailed microscopic description of the electron transfer reaction in an electrochemical environment. The present approach is based on the well-known two state model extended by the novelty that the energy of the two states involved in the electron transfer reaction is computed quantum mechanically as a function of the solvent coordinate, as defined in the Marcus theory, and of the intensity of an external electric field. The solvent conformations defining the reaction coordinate are obtained from classical molecular dynamics and then transferred to the quantum mechanical model. The overall approach has been applied to the electron transfer between a chloride anion and a single crystal Cu(100) electrode. It is found that the solvent exerts a strong influence on the equilibrium geometry of the halide and hence on the relative energy of the two states involved in the electron transfer reaction. Finally, both solvent fluctuations and external field facilitate the electron transfer although solvent effects have a stronger influence.


Absorbable Polydioxanone (PDS) suture provides fewer wound complications than polyester (ethibond) suture in acute Tendo-Achilles rupture repair.
We prospectively studied acute Achilles tendon rupture in patients over a two 2-year period and reviewed the causes, outcome and complications. There were 53 patients included with acute Achilles rupture with minimum follow up period of 6 months. We compared the outcomes including infection rate and Boyden score between the two groups repaired by Polydioxanone and Polyester respectively. All infected cases had a suture repair using the polyester suture. The difference in the infection rate was highly significant between the 2 groups (p=0.001). All 34 patients (100%) in the PDS group had good / excellent results based on the Boyden clinical assessment. Conversely, only 16 patients 9(68.4%) had good or excellent results IN Polyester repair group. Patients treated with a non- absorbable suture (ethibond) material for repair had a higher incidence infection and worse Boyden scores than the absorbable PDS group.


ASSAY OPTIMIZATION AND REGULATION OF UREASE ACTIVITY IN TWO MARINE DIATOMS.
An in vitro urease enzyme assay was developed for the marine diatoms Thalassiosira pseudonana Hasle et Heimdal (clone 3H) and T. weissflogii (Grunow) Fryxell et Hasle (clone Actin). This assay involves the colorimetric measurement of ammonium following the hydrolysis of urea in crude cell homogenates and it is the first assay to account for the rate of nitrogen assimilation in both species grown on urea as the sole nitrogen source. Urease activity was found to be present regardless of nitrogen source, although activities showed distinctly different patterns depending on the species examined and form of nitrogen supplied. Under nitrogen-replete conditions, urease activity in T. pseudonana was present constitutively when grown on NH4+ and upregulated when grown on NO3- or urea. In nitrogen-replete T. weissflogii, urease activity was present at high constitutive levels regardless of the nitrogen source and showed no upregulation. Nitrogen starvation did not upregulate activity in either species.


Predictors of Adverse Outcomes in the Management of Mandibular Fractures.
Mandibular fractures are the most common isolated facial fractures in the United States. Various risk factors have been associated with increased rates of postoperative complications. However, national outcome reports are limited and data are conflicting. Using a national multi-institutional database, the authors sought to analyze 30-day outcomes after mandibular fracture repair and determine risk factors for complications, readmission, and reoperation. Retrospective review of the American College of Surgeons National Surgical Quality Improvement database was performed to identify patients undergoing surgical treatment of mandibular fractures between 2010 and 2015 using current procedural terminology codes. Primary outcomes included: wound complications, overall complications, as well as readmission and reoperation rates. Multivariate regression analysis was performed to adjust for confounders. A total of 953 patients were eligible for analysis. Mean patient age was 34.5 years, 84% were males, and 50% were active smokers. Wound complications, overall complications, 30-day reoperation, and readmission occurred in 4.0%, 7.9%, 2.2%, and 33% of patients, respectively. Age was a significant risk factor for 30-day readmission (odds ratio [OR] = 1.06, P = 0.01), reoperation (OR = 1.05, P = 0.01), and overall complications (OR = 1.03, P = 0.02) on multivariate analysis, and smoking was a significant risk factor for 30-day reoperation (OR = 4.86, P = 0.03). The analysis identified age as an independent risk factor for readmission, reoperation, and overall complications. Smokers were also nearly 5 times as likely to undergo additional surgery. This is particularly important given that over half of patients were active smokers, highlighting the importance of perioperative patient education and smoking cessation within this population.


Facultative heterochromatin formation in rDNA is essential for cell survival during nutritional starvation.
During the cellular adaptation to nutrient starvation, cells temporarily decelerate translation processes including ribosomal biogenesis. However, the mechanisms repressing robust gene expression from the ribosomal gene cluster (rDNA) are unclear. Here, we demonstrate that fission yeast cells facing glucose starvation assemble facultative heterochromatin in rDNA leading to its transcriptional repression. Glucose starvation induces quick dissociation of the ATF/CREB-family protein Atf1 from rDNA, where in turn the histone chaperone FACT is recruited to promote H3K9 methylation and heterochromatinization. We also identify the histone acetyltransferase Gcn5 as a repressor of rDNA heterochromatinization in glucose-rich conditions, and this protein dissociates from rDNA upon glucose starvation. Facultative heterochromatin formation in rDNA requires histone deacetylases Clr3 and both the RNAi-dependent and -independent gene silencing pathways. This is essential in adaptation to starvation since mutants lacking heterochromatin formation in rDNA lead to untimely cell death during glucose starvation.


A secondary abdominal pregnancy with unusual placental implantation in the fallopian tube: a diagnostic challenge.
We reported a case of secondary abdominal pregnancy with placental implantation into the fallopian tube, diagnosed at 16 weeks, in a woman admitted to the emergency room complaining of syncopal attacks. The best approach would be termination of the pregnancy, taking into consideration the high risk to the mother and the low possibility of alive and healthy birth. We had to perform an urgent surgical intervention due to the fact that the patient was in a clinically unstable condition, which was related to hemoperitoneum. If placental implantation is on abdominal organs or vessel the best approach would be to ligate the cord and to leave placenta in situ. Taking into consideration the place of placental implant, the removal of the fallopian tube with the placenta was the safest approach in this case. The best and most acceptable form of treatment would be individualized in case of rare form of ectopic pregnancy.


Measuring Greater Patient-Provider Continuity in a Clinic-First Family Medicine Residency Curriculum.
Continuity is valued by patients, clinicians, and health systems for its association with higher-value care and satisfaction. Continuity is a commonly cited reason for entering primary care; however, it is difficult to achieve in residency settings. We sought to determine the effect of transitioning from a traditional "block" (13 4-week rotations per year) to a "clinic-first" (priority on outpatient continuity) curriculum on measures of continuity in our family medicine residency. For the 3 years prior to and the 4 years following the transition from block to clinic-first curriculum (July 2011-June 2018, n = 51 block resident-years and n = 72 clinic-first resident-years), we measured resident panel size, clinic time, office visits, and both resident- and patient-sided continuity measures. We also defined a new longitudinal continuity measure, "familiar faces," which is the number of patients that a resident saw at least 3 times during residency. The transition from block to clinic-first curriculum increased panel size, clinic time for first- and second-year residents, overall total visits, and total number of clinic visits with paneled patients. Continuity measures demonstrated an increased resident-sided continuity at all training levels, an increase (first-year residents) or unchanged (second- and third-year residents) continuity from the patient perspective, and a near doubling of longitudinal continuity. Redesigning our family medicine residency curriculum from a traditional block schedule to a clinic-first curriculum improved our residents' continuity experience.


Effects of supplementing sow diets with Saccharomyces cerevisiae refermented sorghum dried distiller's grains with solubles from late gestation to weaning on the performance of sows and progeny.
We performed 2 experiments to study the effects of supplementing sow diets with refermented sorghum dried distiller's grains with solubles (SSDDGS) from late gestation to weaning on the performance of sows and their progeny. In Exp. 1, 24 sows at 85 d of gestation were allocated to the following 3 dietary treatments: 1) sows fed a basal diet from late gestation to weaning ( = 8), 2) sows fed a diet with 2% SSDDGS ( = 8), and 3) sows fed a diet with 4% SSDDGS ( = 8). The 4% SSDDGS treatment significantly improved the sows' ADFI, the litter weaning alive rate, and the individual piglet weaning weights and significantly reduced the litter stillbirth rate and the levels of urea N and somatic cell counts (SCC) in the milk. However, the 2% SSDDGS treatment did not alter the performance of the sows or progeny. Therefore, we considered the volume of 4% SSDDGS to be more efficient than 2% SSDDGS. To verify the results of Exp. 1, we performed Exp. 2, in which 60 sows at 85 d of gestation were allocated into the following 2 dietary treatments: 1) sows fed a basal gestation diet from 85 d of gestation to weaning ( = 30) and 2) sows fed a basal diet with 4% SSDDGS from 85 d of gestation to weaning ( = 30). The 4% SSDDGS supplementation tended to increase the sows' ADFI, litter weaning size, litter weight gain during lactation, and individual piglet weaning weight and weight gain during lactation, and it also increased the milk yield and the fat and DM contents of the milk. This treatment also decreased the levels of urea N and SCC in the milk. Therefore, the present study indicates that supplementing sow diets with 4% SSDDGS from late gestation to weaning has the potential to 1) increase sow ADFI, 2) promote progeny growth performance, 3) increase sow milk production and quality, and 4) improve the maternal health status as indicated by improved protein utilization and reduced potential inflammatory response.


Advanced chemical methods in melanin determination.
Among the biopolymers, melanins are unique in many respects. The other essential biopolymers - proteins, nucleic acids, and carbohydrates - are chemically well characterized; their precursors (monomer units) and modes of connection between the monomer units are known, and sequences of their connection can be determined with well-established methodologies. In contrast, we still do not have a method to determine accurately the ratio of various units present in melanins. This is largely because of the chemical properties of melanins, such as their insolubility over a broad range of pH, the heterogeneity in their structural features, and also because of the lack of methods that can split melanin polymers into their monomer units (all other biopolymers can be hydrolysed to the corresponding monomer units). To overcome this difficulty, we developed a rapid and sensitive method for quantitatively analysing eumelanin and pheomelanin in biological samples by chemical degradation methods followed by HPLC determination. This HPLC microanalytical method for characterizing eumelanin and pheomelanin has become a useful tool for the study of melanogenesis. This review will summarize the usefulness and limitations of the various chemical and spectrophotometric methods used to analyse melanins at the biochemical, cellular, and tissue levels. Emphasis is given on the usefulness of 4-amino-3-hydroxyphenylalanine as a specific marker of pheomelanin.


Lamellar germ cell processes: structures for possible interaction between germs cells and Sertoli cells during spermatogonial differentiation and early meiotic prophase.
The recent finding of a stage-dependent topographical relationship of basally located germ cells to Sertoli-Sertoli interspaces in the rat testis ( Ulvik 1983a ) has suggested a focal interaction between Sertoli cells and early germ cells at the sites where 2 Sertoli cells meet over a basal germ cell. Focal, stage-dependent interaction between Sertoli cells and germ cells may require specializations of the germ cell membrane. Therefore, in the present work the surface of spermatogonia and spermatocytes has been studied under the electron microscope throughout the cycle of the seminiferous epithelium. Lamellar processes, 1-3 micron long, were found to emerge from germ cells and protrude into the spaces between the overlying Sertoli cells. The processes appeared on differentiating type A spermatogonia after stage VI, on intermediate and type B spermatogonia, and on leptotene, zygotene, and early pachytene spermatocytes; however, they were not found on type A spermatogonia prior to stage VII or on preleptotene spermatocytes at stage VII. The lamellar processes are thus stage-specific and may be sites of focal interaction with the Sertoli cells. Since the cell processes always protrude into the Sertoli-Sertoli interspaces this finding supports the hypothesis of focal, stage-dependent interaction between early germ cells and Sertoli cells via the narrow Sertoli-Sertoli interspaces.


Pronounced anti-proliferative activity and tumor cell selectivity of 5-alkyl-2-amino-3-methylcarboxylate thiophenes.
5-(2-(4-Methoxyphenyl)ethyl)-2-amino-3-methylcarboxylate thiophene (TR560) is the prototype drug of a recently discovered novel class of tumor-selective compounds that preferentially inhibit the proliferation of specific tumor cell types (e.g. leukemia/lymphoma). Here, we further increased tumor selectivity by simplification of the molecule through replacing the 4-methoxyphenyl moiety by an alkyl chain. Several 2-amino-3-methylcarboxylate thiophene derivatives containing at C-5 an alkyl group consisting of at least 6 (hexyl) to 9 (nonyl) carbon units showed pronounced anti-proliferative activity in the mid-nanomolar range with 500- to 1000-fold tumor cell selectivity. The compounds preferentially inhibited the proliferation of T-lymphoma CEM and Molt/4, prostate PC-3, kidney Caki-1 and hepatoma Huh-7 tumor cells, but were virtually inactive against other tumor cell lines including B-lymphoma Raji and cervix carcinoma HeLa cells. The novel prototype drug 3j (containing a 5-heptyl chain) elicited a cytotoxic, rather than cytostatic activity, already after 4 h of exposure. The unusual tumor selectivity could not be explained by a differential uptake (or efflux) of the drug by sensitive versus resistant tumor cells. Exposure of a fluorescent derivative of 3j revealed pronounced uptake of the drug in the cytoplasm, no visible appearance in the nucleus, and a predominant localization in the endoplasmic reticulum. These observations may be helpful to narrow down the intracellular localization and identification of the molecular target of the 5-substituted thiophene derivatives.


Wang-Bi Tablet Ameliorates DMM-Induced Knee Osteoarthritis through Suppressing the Activation of p38-MAPK and NF-κB Signaling Pathways in Mice.
Traditional Chinese medicine (TCM) exhibits outstanding therapeutic effects on the treatment of osteoarthritis (OA). Wang-Bi tablets (WBTs) have been used in clinics to treat knee osteoarthritis (KOA) by alleviating joint swelling and paining, and thus, the quality of life in patients with KOA was improved. However, its underlying molecular mechanism of anti-inflammatory response remains unclear. Therefore, further investigation is required. This study aimed to explore the function of WBT in KOA mice and uncover the possible molecular mechanisms. Study Design. A KOA model was constructed by destabilizing the medial meniscus (DMM). IL-1β-treated chondrocytes were used to investigate the precise mechanism in vitro. (1) C57BL/6 male mice (8-week-old) were divided into Model, Sham, WBT-L, WBT-M, and WBT-H groups. After intragastric administration of 0.5% CMC-Na or WBT for 4 weeks, inflammation and pathological change were analyzed by ELISA, RT-qPCR, hematoxylin and eosin (H & E) and safranine O staining. (2) Isolated chondrocytes were stimulated with IL-1β followed by WBT-containing serum treatment, and then, the expression of inflammatory cytokines was analyzed by ELISA and RT-qPCR. (3) The effects of WBT on inflammatory signaling cascades in mice knee joint and chondrocytes were detected by WB. The results indicated that WBT could alleviate inflammation and prevent cartilage injury in KOA mice. Compared with 0.5% CMC-Na-treated mice, the serum glycosaminoglycans (GAG) level in WBT-treated mice was notably increased, while the proinflammatory cytokine interleukin- (IL-) 6 level was decreased. In addition, WBT treatment suppressed the activation of NF-κB and p38 signaling pathways both in vivo and in vitro. WBT can effectively inhibit articular cartilage injury and inflammatory response in KOA mice. The protective role of WBT in mice KOA was a result of the downregulation of NF-κB and p38-MAPK signal pathways.


Determination of Double Bond Positions in Polyunsaturated Fatty Acids Using the Photochemical Paternò-Büchi Reaction with Acetone and Tandem Mass Spectrometry.
The positions of double bonds along the carbon chain of methylene interrupted polyunsaturated fatty acids are unique identifiers of specific fatty acids derived from biochemical reactions that occur in cells. It is possible to obtain direct structural information as to these double bond positions using tandem mass spectrometry after collisional activation of the carboxylate anions of an acetone adduct at each of the double bond positions formed by the photochemical Paternò-Büchi reaction with acetone. This reaction can be carried out by exposing a small portion of an inline fused silica capillary to UV photons from a mercury vapor lamp as the sample is infused into the electrospray ion source of a mass spectrometer. Collisional activation of [M - H]- yields a series of reverse Paternò-Büchi reaction product ions that essentially are derived from cleavage of the original carbon-carbon double bonds that yield an isopropenyl carboxylate anion corresponding to each double bond location. Aldehydic reverse Paternò-Büchi product ions are much less abundant as the carbon chain length and number of double bonds increase. The use of a mixture of D0/D6-acetone facilitates identification of these double bonds indicating product ions as shown for arachidonic acid. If oxygen is present in the solvent stream undergoing UV photoactivation, ozone cleavage ions are also observed without prior collisional activation. This reaction was used to determine the double bond positions in a 20:3 fatty acid that accumulated in phospholipids of RAW 264.7 cells cultured for 3 days.


[A case of congenital grouped albinotic spots].
This case report presents a 5-year-old male child with a complaint of poor vision in the left eye for the past 2 years, who sought ophthalmic evaluation. There was no apparent systemic pigment loss, but multiple small, flat, and well-defined white lesions were observed in the retinal pigment epithelium of the left eye. Autofluorescence imaging of the fundus revealed widespread patchy hyperautofluorescence corresponding to the lesions. Fluorescein angiography demonstrated early and stable hyperfluorescence without leakage in these spots. Optical coherence tomography examination revealed thickening and material accumulation in the ellipsoid zone that corresponded to the lesions. Based on clinical findings, the diagnosis of congenital grouped albinotic spots was established.


The Effects of Temperature and Hydrostatic Pressure on Metal Toxicity: Insights into Toxicity in the Deep Sea.
Mineral prospecting in the deep sea is increasing, promoting concern regarding potential ecotoxicological impacts on deep-sea fauna. Technological difficulties in assessing toxicity in deep-sea species has promoted interest in developing shallow-water ecotoxicological proxy species. However, it is unclear how the low temperature and high hydrostatic pressure prevalent in the deep sea affect toxicity, and whether adaptation to deep-sea environmental conditions moderates any effects of these factors. To address these uncertainties we assessed the effects of temperature and hydrostatic pressure on lethal and sublethal (respiration rate, antioxidant enzyme activity) toxicity in acute (96 h) copper and cadmium exposures, using the shallow-water ecophysiological model organism Palaemon varians. Low temperature reduced toxicity in both metals, but reduced cadmium toxicity significantly more. In contrast, elevated hydrostatic pressure increased copper toxicity, but did not affect cadmium toxicity. The synergistic interaction between copper and cadmium was not affected by low temperature, but high hydrostatic pressure significantly enhanced the synergism. Differential environmental effects on toxicity suggest different mechanisms of action for copper and cadmium, and highlight that mechanistic understanding of toxicity is fundamental to predicting environmental effects on toxicity. Although results infer that sensitivity to toxicants differs across biogeographic ranges, shallow-water species may be suitable ecotoxicological proxies for deep-sea species, dependent on adaptation to habitats with similar environmental variability.


Kinetic characterization and regulation of purified glutamine synthetase from brain of Clarias batrachus.
Glutamine synthetase (GS) from brain of Clarias batrachus is purified to about 42-fold and characterized at optimum pH and temperature with respect to its kinetic parameters. Values for apparent Michaelis constant of the enzyme for L-glutamine, hydroxylamine and ADP are 50, 62.5 and 0.833 mM respectively. The very low apparent Km for ADP may be specially related to the expression of GS action under high energy bond and also be evidenced by the requirement of enzyme for a high ionic strength of the ADP. The study is extended by examining the effect of various amino acids and metabolites on GS activity in order to gain further understanding of the changes in kinetics and regulation. It reveals that whereas uridine monophosphate and glutamate act competitively with respect to L-glutamine, carbamylphosphate and asparagine act non-competitively. GS activity is markedly inhibited by leucine, aspartic acid and AMP but not by lysine. ATP and methionine sulfoximine behaved as potent inhibitors of the enzyme in vitro. It is suggested that the teleostean GS has most of the properties similar to those reported for mammalian and avian glutamine synthetases. However, it is proposed that kinetic regulation of this enzyme may play a significant role in ammonia detoxication and rate of formation of glutamine-derived neurotransmitters in fish brain.


Influence of urbanization level and gross domestic product of counties in Croatia on access to health care.
To examine the association of counties' urbanization level and gross domestic product (GDP) per capita on the access to health care. Counties were divided in two groups according to the urbanization level and GDP per capita in purchasing power standards. The number of physicians per 100,000 inhabitants, the number of physicians in hospitals in four basic specialties, physicians' workload, average duration of working week, the average number of insurants per general practice (GP) team, and the number of inhabitants covered by one internal medicine outpatient clinic were compared between predominantly urban and predominantly rural counties and between richer and poorer counties. Our study included only GP teams and outpatient clinics under the contract with the Croatian Institute for Health Insurance. Data on physicians were collected from the Ministry of Health and Social Welfare, the Croatian Institute for Health Insurance, the Croatian Institute for Public Health, and the Croatian Medical Chamber. Data on the contracts with the Croatian Institute for Health Insurance and health care services provided under these contracts were obtained from the database of the Institute, while population and gross domestic product data were obtained from the Database of the Croatian Institute for Statistics. World Health Organization Health for All Database was used for the international comparison of physician's data. There was no significant difference in the total number of physicians per 100,000 inhabitants between predominantly urban and predominantly rural counties (206.9+/-41.0 vs 175.4+/-30.3; P=0.067, t test) nor between richer and poorer counties (194.5+/-49.8 vs 187.7+/-25.3; P=0.703, t test). However, there were significantly fewer GPs per 100,000 inhabitants in rural than urban counties (49.0+/-5.5 vs 56.7+/-4.6; P=0.003, t test). GPs in rural counties had more insurants than those working in urban counties (1.749.8+/-172.8 vs 1.540.7+/-106.3; P=0.004, t test). The working week of specialists in the four observed specialties in hospitals was longer than the recommended 48 hours a week. The lack of physicians, especially in primary health care can lead to a reduced access to health care and increased workload of physicians, predominantly in rural counties, regardless of the counties' GDP.


[Costs and efficacy of type A botulinum toxin for the treatment of essential blepharospasm and hemifacial spasm].
To evaluate the costs and efficacy of type A botulinum toxin in the treatment of essential blepharospasm and hemifacial spasm. Pacients with essential blepharospasm and hemifacial spasm had their files analyzed. All patients were treated with type A botulinum toxin (Dysport) between April 2002 and May 2004 at the Oculoplastic Clinics of "Santa Casa de São Paulo". Twenty-seven patients presented essential blepharospasm and 23 presented hemifacial spasm. Information about the patient's degree of satisfaction after treatment, complaints and personal costs were recorded by a questionnaire, and information about the costs of Dysport treatment were obtained at the administration department of "Santa Casa de São Paulo". Wilcoxon and Mann-Whitney tests were used for statistical analysis. 1- The annual treatment costs were R Dollars 1,239.32 for essential blepharospasm and R Dollars 661.72 for hemifacial spasm. 2- The patient's annual costs were R Dollars 145.48 for essential blepharospasm and R Dollars 6.07 for hemifacial spasm. 3- The hospital's annual costs for the treatment were R Dollars 1,095.84 for essential blepharospasm and R Dollars 535.65 for hemifacial spasm. 4- Dysport treatment is successful in both essential blepharospasm and hemifacial spasm. The costs of essential blepharospasm and hemifacial spasm treatment with Dysport are high, mainly because of the toxin price. On economic analysis of health, we can conclude that this procedure has an excellent cost-benefit ratio.


Staphylococcus aureus RNAIII and Its Regulon Link Quorum Sensing, Stress Responses, Metabolic Adaptation, and Regulation of Virulence Gene Expression.
Staphylococcus aureus RNAIII is one of the main intracellular effectors of the quorum-sensing system. It is a multifunctional RNA that encodes a small peptide, and its noncoding parts act as antisense RNAs to regulate the translation and/or the stability of mRNAs encoding transcriptional regulators, major virulence factors, and cell wall metabolism enzymes. In this review, we explain how regulatory proteins and RNAIII are embedded in complex regulatory circuits to express virulence factors in a dynamic and timely manner in response to stress and environmental and metabolic changes.


Compression of the Left Atrium and Pulmonary Veins Due to Ascending and Descending Aortic Aneurysms.
An 89-year-old female patient presented to our cardiology outpatient clinic complaining of shortness of breath and back pain. Chest X-ray demonstrated a widened mediastinum. Transthoracic echocardiography showed an ascending aortic aneurysm and the modified apical 5-chamber view showed that left atrium was compressed between the ascending and descending aortas. Color Doppler turbulence was also seen in the compressed area. A contrast-enhanced chest computed tomography scan in axial and coronal planes showed that left atrium and pulmonary veins were compressed by ascending and descending aortic aneurysms. Herein, we illustrated this rare condition diagnosed by transthoracic echocardiography in combination with computed tomography.


Energy expenditure and protein requirements after traumatic injury.
Traumatic injury induces hypermetabolism. The degree of hypermetabolism can be variable, depending on the type of injury, the degree of inflammation, body composition, age, and treatment regimens. To estimate metabolic rate in some types of injury, predictive equations have been published. Some of these equations have been tested in validation studies. For other types of injury, equations do not exist. Some expert panels have recommended measuring in lieu of estimating metabolic rate, though studies have not been performed to determine whether clinical outcome is affected by the method used to determine energy requirements. Traumatically injured patients are usually catabolic, but protein needs after traumatic injury continue to be debated. Some suggest that 1.5 g protein per kg body weight is adequate and that any additional protein is simply oxidized, adding to the nitrogen load to be excreted. Alternately, protein intake >2.0 g/kg body weight increases the absolute rate of body protein synthesis, and achievement of nitrogen balance has been associated with survival. Thus, provision of high-protein feeding to achieve nitrogen balance might be worthwhile, even if that balance is achieved at the cost of additional nitrogen production.


Lateralization of verbal memory and unilateral hippocampal sclerosis: evidence of task-specific effects.
This study retrospectively investigated the effect of left (LHS) versus right (RHS) hippocampal sclerosis on verbal memory, measured by means of the Paired Associate Learning and Logical Memory subtests of the Wechsler Memory Scale (WMS) administered as part of a routine preoperative assessment. Patients were selected for the presence of unilateral hippocampal sclerosis by means of preoperative magnetic resonance imaging (MRI) and postoperative neuropathology. The LHS patients (n = 20) were significantly worse on paired associate learning than RHS patients (n = 18), the performance of RHS patients being consistent with normative standards. In contrast, no laterality effect was seen on the immediate and delayed recall of passages; the evidence suggests that both groups performed at a mildly impaired level. It was suggested that the laterality of verbal memory is conditional upon specific task demands in patients with damage to mesial temporal structures.


Chlamydia and mitochondria - an unfragmented relationship.
Presence of pathogens within a eukaryotic cell is apt to generate stress. Such stress eventually leads to host defense responses, which includes, but is not limited to, apoptosis induction and subsequent destruction of the host cell and the pathogen. Obligate intracellular pathogens such as Chlamydia trachomatis are dependent on the survival of the host cell owing to their unique replication niche within a membrane-bound inclusion. Furthermore, being energy parasites, chlamydial development is strictly dependent on the host metabolism. Over the past decade the role of the small non-coding RNAs called microRNAs (miRNAs) have come into focus with respect to the regulation of apoptotic signaling, metabolic homeostasis and bacterial pathogenesis. Effect of Chlamydia infection on the host miRNA profile was hitherto unknown. In our recent work we demonstrated that Chlamydia infection induces and requires an upregulation of the host miRNA, miR-30c-5p (miR-30c) to ameliorate infection induced stress on the host mitochondrial architecture and hinders induction of apoptosis.


Imaging findings of pelvic tumor thrombosis extending from sacral bone metastasis of adrenocortical carcinoma.
We report the imaging findings of a patient with adrenocortical carcinoma who showed pelvic tumor thrombosis extending from sacral bone metastasis. Contrast-enhanced computed tomography demonstrated extensive intraluminal filling defects in the pelvic veins. A lytic lesion in the sacrum was also noted and continuity between the sacral lesion and the filling defect in the branch of pelvic veins was indicated. The filling defects showed increased uptake on positron emission tomography with (18)F-fluorodeoxyglucose and single-photon emission computed tomography with (131)I-iodomethylnorcholesterol, and fusion images with computed tomography aided the localization of the increased uptake areas. Multimodality imaging may be beneficial for the characterization and localization of lesions in patients suspected of having metastatic adrenocortical carcinoma.


Regadenoson Stress Real-Time Myocardial Perfusion Echocardiography for Detection of Coronary Artery Disease: Feasibility and Accuracy of Two Different Ultrasound Contrast Agents.
The aim of this study was to compare the efficacy of myocardial perfusion (MP) and wall motion (WM) analysis obtained with real-time myocardial contrast echocardiography (RTMCE) and two widely used contrast agents in detecting coronary artery disease after injection of the vasodilator regadenoson. One hundred fifty patients were studied at two academic centers using regadenoson (400-μg intravenous bolus) vasodilator stress RTMCE (7.5% Optison infusion [n = 50] or 1.5% Definity infusion [n = 100]). Both MP and WM with RTMCE were analyzed at rest and after regadenoson bolus. Comparisons of WM and MP sensitivity, specificity, and accuracy were made. Quantitative angiography was performed in all patients within 1 month of the regadenoson stress study (>50% and >70% diameter stenosis was considered significant). Reviewers were blinded to all clinical and quantitative angiographic data. Rate-pressure product after regadenoson was higher in Optison than Definity patients (P = .004). Using a 50% diameter stenosis on quantitative angiography as a reference standard, overall sensitivity, specificity, and accuracy for combined WM and MP analysis were not different for both agents (Optison, 77%, 64%, and 73%; Definity, 80%, 74%, and 78%; P = NS). The sensitivity, specificity, and accuracy of WM analysis alone for Optison were 68%, 71%, and 69% compared with 60%, 72%, and 66% for Definity (P = NS). Adding MP analysis improved the sensitivity and accuracy of Definity for detecting both >50% and >70% stenoses (P < .001 vs WM), while MP analysis did not improve the sensitivity of Optison for detecting either >50 or >70% stenoses. RTMCE during regadenoson stress using either Optison or Definity is a rapid and effective method for the detection of coronary artery disease. The ability of MP imaging to improve WM accuracy may depend on the rate-pressure product achieved.


Relaxation with Immersive Natural Scenes Presented Using Virtual Reality.
Virtual reality (VR) can provide exposure to nature for those living in isolated confined environments. We evaluated VR-presented natural settings for reducing stress and improving mood. There were 18 participants (9 men, 9 women), ages 32 ± 12 yr, who viewed three 15-min 360° scenes (an indoor control, rural Ireland, and remote beaches). Subjects were mentally stressed with arithmetic before scenes. Electrodermal activity (EDA) and heart rate variability measured psycho-physiological arousal. The Positive and Negative Affect Schedule and the 15-question Modified Reality Judgment and Presence Questionnaire (MRJPQ) measured mood and scene quality. Reductions in EDA from baseline were greater at the end of the natural scenes compared to the control scene (-0.59, -0.52, and 0.32 μS, respectively). The natural scenes reduced negative affect from baseline ( 1.2 and 1.1 points), but the control scene did not ( 0.4 points). MRJPQ scores for the control scene were lower than both natural scenes (4.9, 6.7, and 6.5 points, respectively). Within the two natural scenes, the preferred scene reduced negative affect ( 2.4 points) more than the second choice scene ( 1.8 points) and scored higher on the MRJPQ (6.8 vs. 6.4 points). Natural scene VR provided relaxation both objectively and subjectively, and scene preference had a significant effect on mood and perception of scene quality. VR may enable relaxation for people living in isolated confined environments, particularly when matched to personal preferences.Anderson AP, Mayer MD, Fellows AM, Cowan DR, Hegel MT, Buckey JC. Relaxation with immersive natural scenes presented using virtual reality. Aerosp Med Hum Perform. 2017; 88(6):520526.


Phase transition in the ABC model.
Recent studies have shown that one-dimensional driven systems can exhibit phase separation even if the dynamics is governed by local rules. The ABC model, which comprises three particle species that diffuse asymmetrically around a ring, shows anomalous coarsening into a phase separated steady state. In the limiting case in which the dynamics is symmetric and the parameter q describing the asymmetry tends to one, no phase separation occurs and the steady state of the system is disordered. In the present work, we consider the weak asymmetry regime q=exp(-beta/N), where N is the system size, and study how the disordered state is approached. In the case of equal densities, we find that the system exhibits a second-order phase transition at some nonzero beta(c). The value of beta(c)=2pi square root 3 and the optimal profiles can be obtained by writing the exact large deviation functional. For nonequal densities, we write down mean-field equations and analyze some of their predictions.


Localization of heparanase in normal and pathological human placenta.
Degradation of extracellular matrix (ECM) components is critical for invasion. Heparan sulphate proteoglycans are abundant in the ECM of the placenta and the decidua, hence their degradation may disassemble the matrix and facilitate placentation and trophoblast invasion. This study investigates the expression of heparanase in normal and pathological placentation using RT-PCR, in-situ hybridization and immunohistochemistry analysis to detect heparanase in specific cells of the placenta and at the fetal-maternal interface throughout pregnancy. Heparanase was observed in villous cytotrophoblasts (CT), syncytial trophoblasts (ST) and in intermediate trophoblast cell columns in normal first trimester, molar and ectopic pregnancies. The heparanase protein was preferentially expressed in the endothelium of fetal capillaries, and to a much lesser extent in larger fetal vessels. Extravillous trophoblasts (EVT) invading the decidua and the maternal vessels were also heparanase positive. In the second and third trimesters, villous CT remained heparanase positive whereas ST showed variable heparanase expression. EVT invading the placental implantation site were also positively stained. A similar pattern was observed in samples obtained from pre-eclamptic placentae and from placenta accreta. Our results indicate consistent expression of heparanase in normal and abnormal placenta, in small fetal vessels and in a variety of trophoblast subpopulations with different invasive potentials.


Role of platelet-rich fibrin on intestinal anastomosis wound healing in a rat.
The aim of the present study is to investigate the role of platelet-rich fibrin (PRF) on the intestinal anastomotic wound healing in a mesenteric ischemia/reperfusion (I/R) rat model. Forty male Sprague Dawley rats were allocated into four groups: Group I (n = 10): anastomosis to normal bowel; Group II (n = 10): anastomosis after I/R injury; Group III (n = 10): anastomosis and PRF; Group IV: anastomosis after I/R and PRF. Animals were followed up for 7 days, then sacrificed. Anastomotic complications, anastomosis bursting pressures and histopathologic evaluations of the anastomoses were the study parameters. The I/R injury caused more anastomotic adhesion and very low anastomotic bursting pressure when compared with the other groups (p < 0.01). Application of PRF onto the bowel, however, dramatically decreased the local complications and significantly increased the anastomosis bursting pressures (p < 0.01). Histologic evaluation of the anastomoses showed almost complete healing in all animals. The mean histologic scores of the animals were not different between the groups. PRF has a beneficial effect on the intestinal healing process by prevention of local complications and increases the tensile strain of the anastomosis. This effect was more prominent, particularly when healing is disrupted. Therefore, we conclude that PRF could be an alternative treatment option to prevent anastomotic complications for elderly, co-morbid and emergency patients.


Atom-by-Atom and Sheet-by-Sheet Chemical Mechanical Polishing of Diamond Assisted by OH Radicals: A Tight-Binding Quantum Chemical Molecular Dynamics Simulation Study.
Ultraflat and damage-free single-crystal diamond is a promising material for use in electronic devices such as field-effect transistors. Diamond surfaces are conventionally prepared by the chemical mechanical polishing (CMP) method, although the CMP efficiency remains a critical issue owing to the extremely high hardness of diamond. Recently, OH radicals have been demonstrated to be potentially useful for improving the CMP efficiency for diamond; however, the underlying mechanisms are still elusive. In this work, we applied our previously developed CMP-specialized tight-binding quantum chemical molecular dynamics simulator to comprehensively elucidate the CMP mechanisms of diamond assisted by OH radicals. Our simulation results indicate that the diamond surface is oxidized by reactions with OH radicals and then a concomitant surface reconstruction takes place due to the distorted and unstable nature of the oxidized diamond surface structure. Furthermore, we interestingly reveal that the reconstruction of the diamond surface ultimately leads to two distinct removal mechanisms: (i) gradual atom-by-atom removal through the desorption of gaseous molecules (e.g., CO2 and H2CO3) and (ii) drastic sheet-by-sheet removal through the exfoliation of graphitic ring structures. Hence, we propose that promoting the oxidation-induced graphitization of the diamond surface may provide a route to further improving the CMP efficiency.


Use of the Facial Artery for Free Functioning Muscle Transfers: An Alternative Pedicle for Salvage in Brachial Plexus Lesions with Vascular Injuries.
Free functional muscle transfer (FFMT) is a salvage procedure recommended in cases of brachial plexus injury with late presentations or failures of primary nerve reconstruction. The workhorse for most authors is the gracilis, and the most common indication is the restoration of elbow flexion. For successful revascularization of the muscle, donor vessels must be in proximity of the site of the muscle fixation and allow direct coaptation to a donor nerve, ideally without the use of nerve grafts. A major problem occurs when patients have sustained concomitant vascular injuries to the subclavian and/or axillary arteries and had previous surgical dissections in the area where the most common vascular pedicles are located. The authors report the use of the rerouted facial vessels as donors in these complex cases. The surgical technique is presented, along with three cases where the procedure was used. The flaps survived in all the patients and grade > 3/5 muscle contraction was observed in the two patients who had adequate follow-up. Conclusion: the use of the facial vessels as donor vessels is an option to revascularize a FFMT in the setting of severe vascular injury to the subclavian and axillary arteries.


External validation of the European risk assessment tool for chronic cardio-metabolic disorders in a Middle Eastern population.
High burden of chronic cardio-metabolic disorders including type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD), and cardiovascular disease (CVD) have been reported in the Middle East and North Africa region. We aimed to externally validate a non-laboratory risk assessment tool for the prediction of the chronic cardio-metabolic disorders in the Iranian population. The predictors included age, body mass index, waist circumference, use of antihypertensive medications, current smoking, and family history of cardiovascular disease and/or diabetes. For external validation of the model in the Tehran lipids and glucose study (TLGS), the Area under the curve (AUC) and the Hosmer-Lemeshow (HL) goodness of fit test were performed for discrimination and calibration, respectively. Among 1310 men and 1960 women aged 28-85 years, 29.5% and 47.4% experienced chronic cardio-metabolic disorders during the 6 and 9-year follow-up, respectively. The model showed acceptable discrimination, with an AUC of 0.72 (95% CI 0.69-0.75) for men and 0.73 (95% CI 0.71-0.76) for women. The calibration of the model was good for both genders (min HL P = 0.5). Considering separate outcomes, AUC was highest for CKD (0.76 (95% CI 0.72-0.79)) and lowest for T2DM (0.65 (95% CI 0.61-0.69)), in men. As for women, AUC was highest for CVD (0.82 (95% CI 0.78-0.86)) and lowest for T2DM (0.69 (95% CI 0.66-0.73)). The 9-year follow-up demonstrated almost similar performances compared to the 6-year follow-up. Using Cox regression in place of logistic multivariable analysis, model's discrimination and calibration were reduced for prediction of chronic cardio-metabolic disorders; the issue which had more effect on the prediction of incident CKD among women. Moreover, adding data of educational levels and marital status did not improve, the discrimination and calibration in the enhanced model. This model showed acceptable discrimination and good calibration for risk prediction of chronic cardio-metabolic disorders in short and long-term follow-up in the Iranian population.


Origin and ablation of the adenosine triphosphate induced atrial fibrillation after circumferential pulmonary vein isolation: effects on procedural success rate.
Adenosine triphosphate (ATP) has been used to provoke dormant pulmonary vein (PV) conduction after circumferential PV isolation (CPVI). However, there have been no systematic studies examining the incidence and the mechanism of ATP-induced atrial fibrillation (AF) following CPVI in paroxysmal AF. In this study, we explore the mechanism of ATP-induced AF and assess the feasibility of eliminating this response by additional radiofrequency (RF) ablation. A total of 300 consecutive patients with paroxysmal AF underwent CPVI. After all PVs were isolated, intravenous ATP (40 mg) was administered during an intravenous isoproterenol (ISP) infusion (5 μg/min). AF was reproducibly induced by ATP in 39 patients. Non-PV foci were confirmed and located in 29 of these patients at the onset of AF, including 27 foci in the superior vena cava (SVC), 1 focus in the crista terminalis, and 1 focus near the antrum of the PV. In all these cases, ATP-induced AF was eliminated after the non-PV foci were successfully ablated. For the other 10 patients, the foci triggering AF could not be confirmed or located due to the transient effect of ATP, thus no further ablation was performed. After a mean follow-up period of 18.7 ± 6.4 (8-24) months, the success rate in the ATP-induced AF group was not significantly different compared with the conventional treatment group who did not exhibit ATP-induced AF (76.9% vs 67.3%; P = 0.25). But in the subgroup of which the ATP-induced AF could be eliminated by additional RF ablation, the success rate was significantly higher than the non-ATP inducible group (86.2% vs 67.3%; P = 0.04). A large proportion of the ATP-induced AF post CPVI were initiated by rapid firing in the SVC. Eliminating this response by additional ablation may have an influence on clinical results of paroxysmal AF ablation.


Subcutaneous recombinant human erythropoietin in patients on CAPD.
The use of recombinant human erythropoietin (rhuEPO) has revolutionized the treatment of renal anemia, but the dose regimens have not been established. We studied the effects of subcutaneous rhuEPO given 4,000U (1 vial) every 5-10 days in 9 patients on continuous ambulatory peritoneal dialysis (CAPD). Ten stable CAPD patients (6 females and 4 males; mean age +/- SEM, 54.4 +/- 5.6 years; mean baseline hemoglobin concentration 7.3 +/- 1.2g/dL) were commenced on s.c. rhuEPO. None of the patients had a history of gastrointestinal bleeding, aluminum overload, sepsis nor receiving androgens. Seven patients were receiving 4,000 U rhuEPO weekly, one patient each was receiving 4,000 U every 5 and 10 days (range, 66.7-89.3 U/kg/week). The dose was adjusted every 4 weeks according to response by altering the dose interval. The mean hemoglobin concentration increased from 7.3 +/- 1.2 g/dL to 10.3 +/- 1.1 g/dL over 8 weeks. There was no significant changes in the serum ferritin, urea, creatinine and potassium levels. One patient required an increase in antihypertensive therapy. We feel that s.c. rhuEPO 4,000 U given on an intermittent basis is effective in the treatment of anemia in CAPD patients. The administration of a single vial each time is convenient and cost sparing. The gradual rise in hematocrit avoids complications.


Spontaneous Anterior Lens Capsule Rupture Of a Patient with Alport Syndrome - A Case Report.
Alport syndrome is a progressive genetic disease which is characterised by glomerulonephritis, sensorineural deafness and ocular abnormalities. We aimed to present a clinical case of a patient with Alport syndrome with spontaneous anterior lens capsule rupture. A 16-year-old male with histologically proven Alport syndrome was hospitalised in the Department of Ophthalmology, University Hospital "Prof. Stoyan Kirkovich", Stara Zagora with low vision, pain, redness, high IOP and rupture of the anterior lenticular capsule of the right eye. Phacoaspiration was successfully performed (Millenium, Bausch& Lomb, Rochester, New York, USA) with the bimanual irrigation-aspiration system (Geuder AG, Heidelberg, Germany) with excellent visual results. As the syndrome is quite rare and can lead to diagnostic difficulties for the ophthalmologist complications such as spontaneous or traumatic rupture of the capsule are not uncommon. In such cases, phacoaspiration is an efficient method for clear lens extraction after ruptures of the anterior lenticular capsule of young patients with Alport syndrome.


SARS-CoV-2 natural infection in animals: a systematic review of studies and case reports and series.
COVID-19 pandemic is essentially a zoonotic disease. In this context, early in 2020, transmission from humans to certain animals began reporting; the number of studies has grown since. To estimate the pooled prevalence of SARS-CoV-2 natural infection in animals and to determine differences in prevalence between countries, years, animal types and diagnostic methods (RT-PCR or serological tests). A systematic literature review with meta-analysis using eight databases. Observational studies were included but analyzed separately. We performed a random-effects model meta-analysis to calculate the pooled prevalence and 95% confidence interval (95% CI) for prevalence studies and case series. After the screening, 65 reports were selected for full-text assessment and included for qualitative and quantitative analyses. A total of 24 reports assessed SARS-CoV-2 infection by RT-PCR, combining a total of 321,785 animals, yielding a pooled prevalence of 12.3% (95% CI 11.6%-13.0%). Also, a total of 17 studies additionally assessed serological response against SARS-CoV-2, including nine by ELISA, four by PRTN, one by MIA, one by immunochromatography (rest, two studies, the method was not specified), combining a total of 5319 animals, yielding a pooled prevalence of 29.4% (95% CI 22.9%-35.9%). A considerable proportion of animals resulted infected by SARS-CoV-2, ranking minks among the highest value, followed by dogs and cats. Further studies in other animals are required to define the extent and importance of natural infection due to SARS-CoV-2. These findings have multiple implications for public human and animal health. One Health approach in this context is critical for prevention and control.


Evaluation of mouse blastocyst implantation rate by morphology grading.
The aim of our study is to observe the relationship between the blastocyst morphology and the implantation rate for mice. Mouse embryos obtained from the superovulated-ICR mice were cultured in vitro from 1-cell zygotes to blastocysts. Mouse blastocysts were then classified into 3 grades: grade I, small blastocysts; grade II, large blastocysts; grade III, hatching blastocysts. They were independently transferred into the uterus of recipient females mated with vasectomized male mice on 96 hours after the zygotes were cultured in vitro. The successful implantation was checked by injection of Chicago Sky Blue 6B on the second day after embryo transfer. Although there was no significant difference in the implantation rates between the grade III and grade II, grade I was significantly decreased, as compared with grade III. Grade I and grade II was also significantly decreased in both the diameter of blastocysts and cell number of inner cell mass (ICM) and trophectoderm (TE), as compared with grade III. These findings indicate that the expanded and hatching blastocyst selections for embryo transfer in in vitro fertilization were evaluated with the high implantation rate.


Mutations of bacteriophage T7 that affect initiation of synthesis of the gene 0.3 protein.
Two different mutations that greatly diminish the rate of synthesis of the gene 0.3 protein of bacteriophage T7 have been characterized. One is in the initiator triplet for the 0.3 protein, changing it from AUG to ACG. This mutation was found to have little effect on binding of ribosomes to the 0.3 mRNA in vitro, although 0.3 protein synthesis was greatly depressed in vitro as well as in vivo. A suppressor mutation that partially restores the wild-type rate of synthesis was found to lie within the 0.3 RNA but not close to the mutant ACG (more than 64 nucleotides away). The second mutation is a G-to-A transition located 11 bases to the 5' side of the initiator AUG. This change eliminates a possible five-base pairing with a sequence near the 3' end of 16S ribosomal RNA, an interaction previous workers have proposed to be important for initiation of protein synthesis. This mutation causes the site of ribosome binding to shift about 15 bases to the 3' side, centering on an internal AUG, but this new site has only a poor potential interaction with 16S RNA. A suppressor mutation that restores the rate of 0.3 protein synthesis to essentially wild-type levels and also restores wild-type ribosome-binding behavior was found to lie adjacent to the original mutation, creating a new four-base complementarity with 16S RNA. These results provide strong support for the idea that a pairing interaction between mRNA and 16S RNA is involved in specific initiation of protein synthesis in Escherichia coli and indicate that this interaction may be important in selecting the site in mRNA at which the ribosomes bind.


Effects of protriptyline and perphenazine in neurotic depressed outpatients.
A four-week comparison of protriptyline 10 mg three times a day and perphenazine 2 mg three times a day, alone and in combination, and a placebo in a group of nonpsychotic depressed outpatients showed no significant differences among any of the treatment groups after both two and four weeks, and a slight trend in favor of the placebo group. A significant positive correlation was observed between changes in hostility and changes in depression, contrary to many commonly held assumptions regarding the relationship between hostility and depression.


D-alanine deprivation of Bacillus subtilis teichoic acids is without effect on cell growth and morphology but affects the autolytic activity.
Using insertional inactivation of the different genes of the dlt operon in Bacillus subtilis, we searched for metabolic and morphological changes caused by D-alanine ester deprivation of lipoteichoic acid and wall teichoic acid. There were no alterations of cell growth, basic metabolism, cellular content of phosphorus-containing compounds, ultrastructure, cell separation, and surface charge. The only alteration observed was an enhancement of endogenous and beta-lactam-induced cell lysis. Since this enhancement is doubtless correlated with the D-alanine ester deprivation of the teichoic acids, the present view based on in vitro experiments, that negatively charged LTA is inhibitory to autolysins, may be questioned. We propose that negatively charged lipoteichoic acid and/or wall teichoic acid serve in vivo to fix the cationic autolysins within the cell wall-membrane complex by electrostatic interaction. Positively charged D-alanine ester substituents decrease the binding capacity of the teichoic acids for autolysins by charge compensation.


The paradox of the serrated sickle erythrocyte: The importance of the red blood cell membrane topography.
Red blood cell rheology and adhesiveness play a key role in the occurrence of vaso-occlusive like events in sickle cell anemia. The present paper reviews counter-intuitive findings supporting that rigid and serrated sickle red blood cells do not initiate vaso-occlusion. Instead, the less rigid red blood cells could initiate vaso-occlusion because of their increased adhesiveness to the vascular wall. We suspect that stiffness of sickle erythrocytes and the topography of RBC membrane are factors affecting adhesion to the endothelium.


Real-world treatment, clinical outcomes and healthcare resource utilization among persons with hemophilia A by age.
Aim: Examine real-world characteristics, treatment patterns, and outcomes among treated persons with hemophilia A (PwHA) stratified by age. Patients & methods: This study utilized US claims data from 1 January 2007-31 July 2018 from the Humana Research Database. Unadjusted comparisons were conducted across PwHA (<18, 18-55, 56-89 years) enrolled in commercial or Medicare Advantage Prescription Drug plans. Results: A total of 294 PwHA were identified; 21.1% experienced ≥1 bleeding event, and 41.2 and 53.1% had evidence of arthropathy or related disorders, and pain, respectively. Along with all-cause and hemophilia-related healthcare resource utilization (HCRU), these were highest among PwHA aged 56-89 years. Conclusion: Insights into treatment, outcomes and HCRU may identify opportunities for enhanced disease management, particularly in older PwHA.


[Gastritis and gastropathy].
Alterations of the stomach mucosa in response to different adverse effects result in various morphological and clinical symptoms. Gastric mucosa alterations can be classified on the bases of diverse viewpoints. It makes this overview difficult, that identical toxic effects may cause different mucosal changes and different toxic agents may produce similar mucosal appearance. The more accurate understanding of the pathological processes which develop in the stomach mucosa needs reconsideration. The authors make an attempt to define gastritis and gastropathy in order to classify and present their features. Gastritis is a histological definition indicating mucosal inflammation. Acute gastritis is caused by infections. The two most important forms of chronic gastritis are metaplastic atrophic gastritis with an autoimmune origin and Helicobacter pylori inflammation. Gastropathy is the name of different structural alterations of the mucosa. Its most important feature is the paucity of inflammatory signs. Gastropathies can be divided into 4 categories based on the nature of the underlying pathological effect, on its morphological appearance and the way of the development. Differential diagnosis is an important pathological and clinical task because different treatment methods and prognosis.


Pharmacokinetics of butafosfan after intravenous and intramuscular administration in piglets.
The pharmacokinetics and bioavailability of butafosfan in piglets were investigated following intravenous and intramuscular administration at a single dose of 10 mg/kg body weight. Plasma concentration-time data and relevant parameters were best described by noncompartmental analysis after intravenous and intramuscular injection. The data were analyzed through WinNolin 6.3 software. After intravenous administration, the mean pharmacokinetic parameters were determined as T1/2λz of 3.30 h, Cl of 0.16 L kg/h, AUC of 64.49 ± 15.07 μg h/mL, Vss of 0.81 ± 0.44/kg, and MRT of 1.51 ± 0.27 h. Following intramuscular administration, the Cmax (28.11 μg/mL) was achieved at Tmax (0.31 h) with an absolute availability of 74.69%. Other major parameters including AUC and MRT were 48.29 ± 21.67 μg h/mL and 1.74 ± 0.29 h, respectively.


Defining the physiologically normal coating and pathological deposit: an analysis of sulfur-containing moieties and pellicle thickness on hydrogel contact lenses.
Historically, biochemical studies of the interaction between tears and hydrogel contact lenses have not been coordinated with the study of the morphological ultrastructure of the phenomena. Moreover, terms that have distinct and different meanings--pellicle, coating, deposit, and biofilm--have been used interchangeably and often incorrectly when applied within the context of the general field of contact lens biotechnology to describe the tear-polymer interaction. We describe our elucidation of morphological and elemental characteristics of the normal pellicle that forms on the lens surface and urge standard use of the word "pellicle" to specify this entity. Fourteen worn hydrogel lenses (8 Group 1 and 6 Group 4 lenses according to the FDA classification) were rinsed, quartered, and fixed or dried, depending on the analysis to be performed. Scanning electron microscopy (SEM) was used to examine the morphology of the pellicle and quantify its thickness. X-ray analysis was used to detect elements associated with the anterior, central, and posterior portions of the lenses and their relative distribution. A distinctive morphological pellicle ranging from 0.1 to 8.6 microns was present on 12 of the 14 lenses. The pellicle was thicker on the Group 4 lenses than on the Group 1 lenses (P < 0.003). However, the pellicle on Group 1 lenses became thicker with increasing lens age (P < 0.02), but not as thick as on Group 4 lenses. Morphologically distinct lipid or jelly bump deposits were observed at the surface of both lenses from a single patient wearing 2 week old Group 4 lenses. Eleven lenses had sulfur-bearing tear components on the anterior zone. Sulfur was deposited within the matrix of nine lenses. The sulfur containing moieties were more prevalent on Group 4 lenses (P < 0.002). More sulfur was assayed on older lenses (P < 0.004). The anterior lens zone had more sulfur-bearing tear components than did the posterior or center zones (P < 0.05). The physiologically normal pellicle is a distinct morphological entity covering the anterior lens surface. Abnormal deposits such as the discrete microgel region, known as jelly bumps, are not part of the physiologically normal pellicle at the anterior lens surface and have the potential to induce pathology. Sulfur-containing moieties within the matrix may represent the breakdown of large proteins and mucoproteins or intact proteins, as well as contaminants such as cosmetics and environmental pollutants. It is also possible that entire small proteins, such as lysozyme, impregnate the matrix. The moieties that become entrapped within the matrix or rigidly adhere to the matrix should be considered true deposits.


Comparison of 3 Different Perioperative Care Models for Patients With Hip Fractures Within 1 Health Service.
Orthogeriatric care models have been introduced within many health-care facilities to improve outcomes for hip fracture patients. This study aims to evaluate differences in care between 3 models, an orthopedic model, a geriatric model, and a comanaged model. A retrospective analysis was conducted for hip fracture patients treated at Western Health between November 2012 and March 2014. All patients aged 65 years or older were included in the analysis. There were 183 patients in the orthopedic model, 137 in the geriatric model, and 126 in the comanaged model. Demographics and clinical characteristics were similar across the 3 models. Length of stay, mortality, and discharge destination were also consistent across the 3 groups. However, groups involving geriatricians were more likely to receive preoperative medical assessments, have greater recognition of postoperative medical problems, and have implementation of long-term osteoporosis management. The involvement of geriatricians in perioperative care models resulted in more comprehensive medical care without impacting length of stay, mortality, or discharge destination.


Real-Time Visualizing Mitophagy-Specific Viscosity Dynamic by Mitochondria-Anchored Molecular Rotor.
Mitophagy, as an evolutionarily conserved cellular process, plays a crucial role in preserving cellular metabolism and physiology. Various microenvironment alterations assigned to mitophagy including pH, polarity, and deregulated biomarkers are increasingly understood. However, mitophagy-specific viscosity dynamic in live cells remains a mystery and needs to be explored. Here, a water-soluble mitochondria-targetable molecular rotor, ethyl-4-[3,6-bis(1-methyl-4-vinylpyridium iodine)-9 H-carbazol-9-yl)] butanoate (BMVC), was exploited as a fluorescent viscosimeter for imaging viscosity variation during mitophagy. This probe contains two positively charged 1-methyl-4-vinylpyridium components as the rotors, whose rotation will be hindered with the increase of environmental viscosity, resulting in enhancement of fluorescence emission. The results demonstrated that this probe operates well in a mitochondrial microenvironment and displays an off-on fluorescence response to viscosity. By virtue of this probe, new discoveries such as the mitochondrial viscosity will increase during mitophagy are elaborated. The real-time visualization of the mitophagy process under nutrient starvation conditions was also proposed and actualized. We expect this probe would be a robust tool in the pathogenic mechanism research of mitochondrial diseases.