Development of a new risk stratification system for patients with newly diagnosed multiple myeloma using R-ISS and 18F-FDG PET/CT.
In multiple myeloma (MM), a high number of focal lesions (FL) detected using positron emission tomography/computed tomography (PET/CT) was found to be associated with adverse prognosis. To design a new risk stratification system that combines the Revised International Staging System (R-ISS) with FL, we analyzed the data of 380 patients with newly diagnosed MM (NDMM) who underwent 18F-fluorodeoxyglucose (18F-FDG) PET/CT upon diagnosis. The K-adaptive partitioning algorithm was adopted to define subgroups with homogeneous survival. The combined R-ISS with PET/CT classified NDMM patients into four groups: R-ISS/PET stage I (n = 31; R-ISS I with FL ≤ 3), stage II (n = 156; R-ISS I with FL > 3 and R-ISS II with FL ≤ 3), stage III (n = 162; R-ISS II with FL > 3 and R-ISS III with FL ≤ 3), and stage IV (n = 31; R-ISS III with FL > 3). The 2-year overall survival rates for stages I, II, III, and IV were 96.7%, 89.8%, 74.7%, and 50.3%. The 2-year progression-free survival rates were 84.1%, 64.7%, 40.8%, and 17.1%, respectively. The new R-ISS/PET was successfully validated in an external cohort. This new system had a remarkable prognostic power for estimating the survival outcomes of patients with NDMM. This system helps discriminate patients with a good prognosis from those with a poor prognosis more precisely.


You Can't Have It All: The Experience of Academic Hospitalists During Pregnancy, Parental Leave, and Return to Work.
The United States lags behind most other countries regarding the support for working mothers and parental leave. Data are limited to describe the experience of female hospital medicine physicians during pregnancy, parental leave, and their return to work in academic hospital medicine. We conducted a qualitative descriptive study including interviews with 10 female academic hospitalists chosen from institutions across the country that are represented in Society of Hospital Medicine (SHM) Committees. Interview guides were based on the following domains: experience in pregnancy, parental leave, and return to work. Interviews were recorded, transcribed verbatim, and analyzed using a general inductive approach to theme analysis using the ATLAS.ti software (Scientific Software Development GmbH, Berlin, Germany). Women in hospital medicine experience the following six common challenges in their experience as new parents, each of which has the potential to impact their career trajectory, wellness, and are associated with areas for institutional improvement: (1) access to paid parental leave, (2) physical challenges, (3) breastfeeding, (4) career opportunities, (5) colleague responses, and (6) empathy in patient care.


Estrogen regulation of vascular endothelial growth factor in breast cancer in vitro and in vivo: the role of estrogen receptor alpha and c-Myc.
The role of c-Myc in estrogen regulation of vascular endothelial growth factor (VEGF) and of the vasculature function has been investigated in breast cancer cells and tumors. The studies were performed on MCF7 wild-type cells and MCF7-35im clone, stably transfected with an inducible c-Myc gene. In vitro and ex vivo methods for investigating molecular events were integrated with in vivo magnetic resonance imaging of the vascular function. The results showed that the c-Myc upregulation by estrogen is necessary for the transient induction of VEGF transcription; however, overexpression of c-Myc alone is not sufficient for this induction. Furthermore, both c-Myc and the activated estrogen receptor alpha (ERalpha) were shown to co-bind the VEGF promoter in close proximity, indicating a novel mechanism for estrogen regulation of VEGF. Studies of long-term estrogen treatment and overexpression of c-Myc alone demonstrated regulation of stable VEGF expression levels in vitro and in vivo, maintaining steady vascular permeability in tumors. However, withdrawal of estrogen from the tumors resulted in increased VEGF and elevated vascular permeability, presumably due to hypoxic conditions that were found to dominate VEGF overexpression in cultured cells. This work revealed a cooperative role for ERalpha and c-Myc in estrogen regulation of VEGF and the ability of c-Myc to partially mimic estrogen regulation of angiogenesis. It also illuminated the differences in estrogen regulation of VEGF during transient and long-term sustained treatments and under different microenvironmental conditions, providing a complementary picture of the in vitro and in vivo results.


The effect of landing surface on the plantar kinetics of chinese paratroopers using half-squat landing.
The objective of the study was to determine the effect of landing surface on plantar kinetics during a half-squat landing. Twenty male elite paratroopers with formal parachute landing training and over 2 years of parachute jumping experience were recruited. The subjects wore parachuting boots in which pressure sensing insoles were placed. Each subject was instructed to jump off a platform with a height of 60 cm, and land on either a hard or soft surface in a half-squat posture. Outcome measures were maximal plantar pressure, time to maximal plantar pressure (T-MPP), and pressure-time integral (PTI) upon landing on 10 plantar regions. Compared to a soft surface, hard surface produced higher maximal plantar pressure in the 1(st) to 4(th) metatarsal and mid-foot regions, but lower maximal plantar pressure in the 5(th) metatarsal region. Shorter T- MPP was found during hard surface landing in the 1(st) and 2(nd) metatarsal and medial rear foot. Landing on a hard surface landing resulted in a lower PTI than a soft surface in the 1(st)phalangeal region. For Chinese paratroopers, specific foot prosthesis should be designed to protect the1(st) to 4(th)metatarsal region for hard surface landing, and the 1(st)phalangeal and 5(th)metatarsal region for soft surface landing. Key PointsUnderstanding plantar kinetics during the half-squat landing used by Chinese paratroopers can assist in the design of protective footwear.Compared to landing on a soft surface, a hard surface produced higher maximal plantar pressure in the 1(st) to 4(th) metatarsal and mid-foot regions, but lower maximal plantar pressure in the 5(th) metatarsal region.A shorter time to maximal plantar pressure was found during a hard surface landing in the 1(st) and 2(nd) metatarsals and medial rear foot.Landing on a hard surface resulted in a lower pressure-time integral than landing on a soft surface in the 1(st) phalangeal region.For Chinese paratroopers, specific foot prosthesis should be designed to protect the 1(st) to 4(th) metatarsal region for a hard surface landing, and the 1(st) phalangeal and 5(th) metatarsal region for a soft surface landing.


Single frequency sound propagation in flat waveguides with locally reactive impedance boundaries.
A coherent image source method is presented for evaluating single frequency sound propagation from a point source in a flat waveguide with two infinite and parallel locally reactive boundaries. The method starts from formulating reflections of the spherical sound radiation into integrals of plane wave expansion, and the analytical evaluation of the integrals is simplified by introducing a physically plausible assumption that wave front shapes remain the same before and after each reflection on a reflective boundary. The proposed model can determine coherently the sound fields at arbitrary receiver locations in a flat waveguide, even when one boundary is highly sound absorptive. Being compared with the classical wave theory and the existing coherent ray-based methods, it is shown that the proposed method provides considerable accuracy and advantages to predict sound propagation in flat waveguides with a sound absorptive ceiling and a reflective floor over a broad frequency range, particularly at large distances from the source where the existing methods are problematic.


Effects of ethephon, ethylene, and 2,4-dichlorophenoxyacetic Acid on asexual embryogenesis in vitro.
Asexual embryogenesis in Daucus carota L. ;Queen Anne's Lace' callus was suppressed by Ethephon, ethylene, and 2,4-dichlorophenoxyacetic acid (2,4-D). The Ethephon effect could be attributed to volatile and nonvolatile substances. The volatile component was probably entirely ethylene. Ethylene was liberated in the cultures in direct proportion to Ethephon added to the medium. Autoclaving of Ethephon caused a substantial decrease of measurable ethylene. Continuous exposure of callus to 5 mul/l ethylene depressed somatic cell embryogenesis, but not markedly. Depression of embryogenesis by 2,4-D was unrelated to ethylene evolution.


Pulmonary embolism from a popliteal vein aneurysm.
This is the first report of a venous aneurysm detected by radionuclide venography. Aneurysms of the popliteal vein are very rare. Described here is a case of a saccular popliteal venous aneurysm that presented as dyspnea secondary to pulmonary embolism. In this case, there was recurrent PE despite anticoagulant therapy. Almost all such aneurysms are associated with PE, about half of which are recurrent. This report demonstrates another useful aspect of obtaining a simultaneous radionuclide venogram when performing a perfusion lung scan with Tc-99m MAA.


Interaction of smooth pursuit and the vestibuloocular reflex in three dimensions.
1. What is the neural mechanism of vestibuloocular reflex (VOR) cancellation when a subject fixates a target moving with the head? One theory is that the moving target evokes pursuit eye movements that add to and cancel the VOR. A recent finding with implications for this theory is that eye velocity vectors of both pursuit and the VOR vary with eye position, but in different ways, because pursuit follows Listing's law whereas the VOR obeys a "half-Listing" strategy. As a result, pursuit cannot exactly cancel the VOR in most eye positions, and so the pursuit superposition theory predicts an eye-position-dependent pattern of residual eye velocities during cancellation. To test these predictions, we measured eye velocity vectors in humans during VOR, pursuit, and cancellation in response to torsional, vertical, and horizontal stimuli with the eyes in different positions. 2. For example, if a subject is rolling clockwise (CW, frequency 0.3 Hz, maximum speed 37.5 deg/s) while looking 20 deg up, the VOR generates an eye velocity that is mainly counterclockwise (CCW), but also leftward. If we then turn on a small target light, located 20 deg up and moving with the subject, then pursuit superposition predicts that the CCW component of eye velocity will shrink and the horizontal component will reverse, from leftward to rightward. This pattern was seen in all subjects. 3. Velocities depended on eye position in the predicted way; e.g., when subjects looked 20 deg down, instead of 20 deg up, during CW roll, the reversal of horizontal eye velocity went the other way, from rightward to leftward. And when gaze was 20 deg right or left, analogous reversals occurred in the vertical eye velocity, again as predicted. 4. Analogous predictions for horizontal and vertical stimulation were also borne out by the data. For example, when subjects rotated rightward while looking 20 deg up, the VOR response was leftward and CCW. When the target light switched on, the torsional component of the response reversed, becoming CW. And analogous predictions for other eye positions and for vertical stimulation also held. 5. For all axes of stimulation and all eye positions, eye velocity during cancellation was roughly parallel with the gaze line. This alignment is predicted by pursuit superposition and has the effect of reducing retinal image slip over the fovea. 6. The fact that the complex dependence of eye velocity on the stimulation axis and eye position predicted by pursuit superposition was seen in all subjects and conditions suggests strongly that the VOR indeed is canceled additively by pursuit. However, eye velocities during cancellation were consistently smaller than predicted. This shrinkage indicates that a second mechanism, besides pursuit superposition, attenuates eye velocities during cancellation. The results can be explained if VOR gain is reduced by approximately 30%, and if, in addition, pursuit is driven by retinal slip rather than reconstructed target velocity in space.


Genetic Polymorphisms of Alcohol Metabolizing Enzymes and Alcohol Consumption are Associated With Asymptomatic Cardiac Remodeling and Subclinical Systolic Dysfunction in Large Community-Dwelling Asians.
Excessive consumption of alcoholic beverages is associated with cardiac remodeling and cardiomyopathy. We examined the possible association of alcohol use, common Asian genetic variants in genes involved in alcohol metabolism, and cardiac structures/functions alterations. A prospective, community-dwelling survey among individuals with available complete echocardiography examined the associations of alcohol use, cardiac structure/functions, and three common alcohol metabolizing genetic variants, including aldehyde dehydrogenase 2 (ALDH2), alcohol dehydrogenase 1B (ADH1B) and cytochrome P450 (CYP) isoform 2E1 (CYP2E1). Among 1577 participants (mean age: 53 ± 9, 59.7% female), we observed that in subjects with more frequent weekly ethanol intake showed greater left ventricle (LV) mass, more impaired diastolic functions, and reduced global longitudinal strain (GLS), systolic (SRs) and early diastolic strain rates (SRe) (P<0.05). After propensity matching for clinical confounders (n = 330:30 for frequent users and non-users), frequent alcohol use and subjects carrying ALDH2 (A/G or A/A), ADH1B (A/A) or CYP2E1(T/C or T/T) polymorphisms were all associated with worse GLSRs and GLSRe, with combined alcohol use and any given genetic variant aggravated these associations (all P < 0.05). Finally, we observed Gene-Gene synergistic effects on LV functional decline in frequent alcohol users by using linear mixed effect model (all interaction P < 0.05). Among East Asians, even moderate alcohol consumption can confer subclinical adverse effects on cardiac systolic functions, which was most pronounced in subjects carrying common variants in alcohol metabolizing genes. These findings challenge the notion of beneficial influences of less heavy ethanol consumption on the heart, especially among East Asians. This study evaluated the association of level of alcohol consumption and genetic variants in genes involved in alcohol metabolism with changes in cardiac function in East Asians. Even moderate alcohol use conferred subclinical adverse effects on cardiac systolic functions, which were most pronounced in subjects carrying common alcohol metabolizing genes.


Religious aspects of assisted reproduction
Human response to new developments regarding birth, death, marriage and divorce is largely shaped by religious beliefs. When assisted reproduction was introduced into medical practice in the last quarter of the twentieth century, it was fiercely attacked by some religious groups and highly welcomed by others. Today, assisted reproduction is accepted in nearly all its forms by Judaism, Hinduism and Buddhism, although most Orthodox Jews refuse third party involvement. On the contrary assisted reproduction is totally unacceptable to Roman Catholicism, while Protestants, Anglicans, Coptic Christians and Sunni Muslims accept most of its forms, which do not involve gamete or embryo donation. Orthodox Christians are less strict than Catholic Christians but still refuse third party involvement. Interestingly, in contrast to Sunni Islam, Shi'a Islam accepts gamete donation and has made provisions to institutionalize it. Chinese culture is strongly influenced by Confucianism, which accepts all forms of assisted reproduction that do not involve third parties. Other communities follow the law of the land, which is usually dictated by the religious group(s) that make(s) the majority of that specific community. The debate will certainly continue as long as new developments arise in the ever-evolving field of assisted reproduction.


Clinical outcome of jejunal pouch double-tract reconstruction after total gastrectomy.
The importance of the duodenal passage and the need for pouch reconstruction after total gastrectomy are matters of controversy. Twenty consecutive patients with early gastric cancer were studied 20who underwent jejunal pouch double-tract (JPD) reconstruction after total gastrectomy. Nutritional variables were examined for > or =10 years postoperatively. The mean operation time was 204 minutes. There was no anastomotic leakage and no hospital mortality. Anastomotic stenosis between the esophagus and a jejunal pouch developed in 2 patients (10%), and reflux esophagitis was observed in 4 (20%). Symptoms were controlled by conserva tive treatment within 3 years after surgery. Body mass indices in all patients were significantly decreased from 1 month (p<0.05) to 10 years (p<0.005) after the operation. The mean body weight decrease occurring during the first to the tenth postoperative year was 12.7% overall, but 17.8% and 9.1% in patients aged > or =60 years and <60 years, respectively. The body weight decreases from 3 (p<0.05) to 6 (p<0.01), and at 9 years (p<0.01) were significantly lower before 60 years of age than after. JPD reconstruction facilitates long-term recovery of body weight after total gastrectomy and should be considered before the aged of 60.


Inhibition of cytochrome P450-mediated metabolism enhances ex vivo susceptibility of Fasciola hepatica to triclabendazole.
A study has been carried out to investigate whether the action of triclabendazole (TCBZ) against Fasciola hepatica is altered by inhibition of drug metabolism. The cytochrome P450 (CYP P450) system was inhibited using piperonyl butoxide (PB). The Oberon TCBZ-resistant and Cullompton TCBZ-susceptible isolates were used for these experiments. The CYP P450 system was inhibited by a 2 h pre-incubation in PB (100 mum). Flukes were then incubated for a further 22 h in NCTC medium containing either PB; PB+nicotinamide adenine dinucleotide phosphate (NADPH) (1 nm); PB+NADPH+TCBZ (15 microg/ml); or PB+NADPH+TCBZ.SO (15 microg/ml). Morphological changes resulting from drug treatment and following metabolic inhibition were assessed using scanning electron microscopy. After treatment with either TCBZ or TCBZ.SO alone, there was greater disruption to the TCBZ-susceptible than the resistant isolate. However, co-incubation with PB and TCBZ/TCBZ.SO lead to more severe surface changes to the TCBZ-resistant Oberon isolate than with each drug on its own. With the TCBZ-susceptible Cullompton isolate, there was limited potentiation of drug action, and only with TCBZ.SO. The results support the concept of altered drug metabolism in TCBZ-resistant flukes and this process may play a role in the development of drug resistance.


A Review on the Role of Endogenous Neurotrophins and Schwann Cells in Axonal Regeneration.
Injury to the peripheral nerve is traditionally referred to acquired nerve injury as they are the result of physical trauma due to laceration, stretch, crush and compression of nerves. However, peripheral nerve injury may not be completely limited to acquired physical trauma. Peripheral nerve injury equally implies clinical conditions like Guillain-Barré syndrome (GBS), Carpal tunnel syndrome, rheumatoid arthritis and diabetes. Physical trauma is commonly mono-neuropathic as it engages a single nerve and produces focal damage, while in the context of pathological conditions the damage is divergent involving a group of the nerve causing polyneuropathy. Damage to the peripheral nerve can cause a diverse range of manifestations from sensory impairment to loss of function with unpredictable recovery patterns. Presently no treatment option provides complete or functional recovery in nerve injury, as nerve cells are highly differentiated and inert to regeneration. However, the regenerative phenotypes in Schwann cells get expressed when a signalling cascade is triggered by neurotrophins. Neurotrophins are one of the promising biomolecules that are released naturally post-injury with the potential to exhibit better functional recovery. Pharmacological intervention modulating the expression of these neurotrophins such as brain-derived neurotrophic factor (BDNF) and pituitary adenylyl cyclase-activating peptide (PACAP) can prove to be a significant treatment option as endogenous compounds which may have remarkable innate advantage showing maximum 'biological relevance'.


Effects of therapeutic recreation on the brain quotient in the elderly dementia patients.
[Purpose] This study investigated how participation in a recreation program influences electroencephalogram changes in the demented elderly. [Subjects] Fourteen patients were included in the experimental group and 18 in the control group. [Methods] They had no regular exercise habits, and walked independently, and scored 11-23 points on the Mini-Mental State Examination, and thus had no apraxia and could communicate. To empirically verify changes in electroencephalograms of the demented elderly for depression, sleep disorder, and life quality through their participation in the therapeutic recreation program, male and female citizens >65 years old at a geriatric hospital were included. The experimental group attended therapeutic recreation programs regularly for 3 months and control group did not. [Results] Electroencephalogram values were higher in the experimental than in the control group, demonstrating that the therapeutic recreation program enhances electroencephalogram values. However, post-program electroencephalograms between the two groups showed minor differences for all variables, except for the anti-stress index and brain quotient. [Conclusion] The therapeutic recreation program caused changes in brain activation, and this method revealed the relation between the activity program and emotion via the anti-stress index.


[Current Status and Future Directions of Hepatocellular Carcinoma Surveillance Test Based on Cost-effective Analysis].
Detection of hepatocellular carcinoma (HCC) at an early stage enables patients to receive curative treatment with survival gains. Current international liver society guidelines recommend the enrollment of patients at high risk for HCC in surveillance programs. In Korea, surveillance for HCC advocated for patients with chronic hepatitis B, chronic hepatitis C, and liver cirrhosis. The established surveillance tool for HCC is liver ultrasonography plus serum alpha-fetoprotein measurement every 6 months. However, there would be obstacles to the improvement of efficacy and cost-effectiveness of the HCC surveillance test. Assessing who is at risk of developing HCC remains incompletely validated. Also, which surveillance tools to use according to patients' characteristics are controversial. The present paper reviews the latest knowledge regarding the strategies and cost-effectiveness of HCC surveillance.


Lactoferrin in the gingival crevice as a marker of polymorphonuclear leucocytes in periodontal diseases.
This study examined lactoferrin (LF) levels in gingival crevicular fluid (GCF) and set out to test the hypothesis that LF could act as a marker of crevicular polymorphonuclear leucocytes (PMN). Therefore, 2 experiments were conducted: (a) to quantify total LF (ng/30 s sample) in GCF; (b) to correlate LF levels (ng/microliters) and PMN numbers (PMNs/microliters) in gingival crevicular washings (GCW). GCF was collected from 71 sites in a total of 22 patients. These sites were classified on the basis of clinical indices of gingivitis (GI) and pocket depth (PD) into three clinical groups: 'healthy', 'gingivitis' and 'periodontitis'. GCWs were obtained from an additional 63 sites in 21 patients. LF in GCF and GCWs was assayed by a sandwich ELISA. Total leucocyte and differential counts were performed on the GCWs. GCF LF (ng/30 s) correlated positively with GI (r = 0.418, p < 0.001), PD (r = 0.415, p < 0.001) and GCF volume (r = 0.624, p < 0.001). Gingivitis (n = 21) and periodontitis sites (n = 24) demonstrated significantly higher (p < 0.05) total GCF LF than healthy (n = 26) sites. In GCWs LF (ng/microliters) showed stronger correlations with clinical indices (GI: r = 0.452, PD: r = 0.513, p < 0.001) than did PMN numbers (PMNs/microliters) (GI: r = 0.279, PD: r = 0.388, p < 0.05). LF correlated strongly with PMNs in GCWs (r = 0.531, p < 0.001) and provides a simple and effective marker of crevicular PMN numbers.


An in vitro rat diaphragmatic fatigue model induced by combined hypoxic and hypercapnic acidosis and the effect of salmeterol.
Hypoxia or hypercapnia impairs diaphragmatic contractility and induces fatigue. However, little is known about the combined effect of hypoxic and hypercapnic acidosis (HHA) on diaphragmatic fatigue. In this study, a gas mixture (21% O2, 12% CO2 and 67% N2) was used to produce HHA-induced rat diaphragmatic fatigue. Force-frequency relationships and twitch characteristics including peak twitch tension (PTT), time to peak tension (TPT), half relaxation time (1/2RT), maintaining tension (MT) and direct-muscle-stimulation tension (MST) were measured in diaphragm preparations from male SD rats. The HHA gas mixture attenuated force at all frequencies (5-120 Hz) and decreased PTT, MT and MST significantly. Aminophylline, a positive control drug, blocked the negative inotropic effect of HHA in a dose-dependent manner. Moreover, salmeterol, a long-acting beta2-adrenoceptor agonist, inhibited the harmful effect of HHA at high frequencies (40-120 Hz), but without effect on MT and MST. These results suggest that an in vitro HHA-induced rat diaphragmatic fatigue model could be established by aerating with the gas mixture, which may be an optimal model to screen effective drugs for diaphragmatic fatigue. Furthermore, salmeterol may play a protective role in HHA-induced impairment.


Evidence for conservation of ferritin sequences among plants and animals and for a transit peptide in soybean.
Ferritin is a large multisubunit protein that stores iron in plants, animals, and bacteria. In animals, the protein is mainly cytoplasmic and is highly conserved, while in plants ferritin is found in chloroplasts and other plastids. Ferritin is synthesized in plants as a larger precursor of the mature subunit. There is no sequence information for ferritin from plants, except an NH2-terminal peptide of 35 residues which shows little similarity to any known ferritin sequences or transit peptides (Laulhere, J. P., Laboure, A. M., and Briat, J. F. (1989) J. Biol. Chem. 264, 3629-3635). To understand the genetic origin and the location of ferritin synthesis in plant cells, as well as the structure of ferritin from plants, we have sequenced both CNBr peptides from pea seed ferritin and nucleotides of a soybean hypocotyl ferritin cDNA, identified using a frog ferritin cDNA as a probe. Comparison of pea and soybean sequences showed an identity of 89%. Alignment of the plant ferritin sequences with animal ferritins showed 55-65% sequence identity in the common regions. However, a peptide of 28 amino acids extended the NH2 terminus of the plant ferritins. Furthermore, the cDNA encoded additional amino acids which appear to be a transit peptide. None of the sequences in soybean ferritin were found in the tobacco chloroplast genome, suggesting, as does the transit peptide, a nuclear location of ferritin gene(s) in plants. Plant ferritin mRNA is 400-500 nucleotides longer than animal ferritin mRNAs, a difference accounted for in part by the extra peptides encoded. The size of soybean ferritin mRNA was constant in different tissues but expression varied in different tissues (leaf greater than hypocotyl). Thus, higher plants and animal ferritins display sequence homology and differential tissue expression. An ancient, common progenitor apparently gave rise to contemporary eukaryotic ferritins after specific modifications, e.g. transport to plasmids.


The safety, efficacy, and pharmacokinetics of esmolol for blood pressure control immediately after repair of coarctation of the aorta in infants and children: a multicenter, double-blind, randomized trial.
Blood pressure control is important after repair of coarctation of the aorta. We report the first prospective multi-institutional trial addressing the safety and efficacy of esmolol after repair of coarctation of the aorta in infants and children. The primary objective of this phase IIIb, multicenter, double-blind, randomized, dose-ranging trial was the efficacy of esmolol to control hypertension. Candidates included subjects younger than 6 years and weighing 2.5 kg or more who underwent surgical intervention for coarctation of the aorta and required therapy for systemic hypertension. One hundred sixteen subjects received esmolol: 36 received a low dose (125 microg/kg), 43 received a medium dose (250 microg/kg), and 37 received a high dose (500 microg/kg). The primary outcomes were the change in systolic blood pressure and the need for additional antihypertensive rescue medication 5 minutes after the initiation of esmolol. All dose groups showed a significant decrease from baseline in systolic blood pressure (-9.6 +/- 16.3 mm Hg, P < .001). There were no differences in systolic blood pressure response at 5 minutes between dose groups (high, medium, or low) or age groups. The need for rescue medication at 5 minutes was not different between dose groups. All dose groups showed similar incidences of adverse events. There were no serious adverse events. Esmolol can be administered safely to patients younger than 6 years after repair of coarctation of the aorta. In the dose range of 125 to 500 microg/kg, esmolol significantly decreased systolic blood pressure.


Complementary anchor PCR of rearranged variable T-cell receptor beta-chain cDNA regions.
Sequencible amplificates comprising the variable cDNA sequences of the rearranged T-cell receptor (TCR) beta-chain were obtained from the T-leukemia cell line Jurkat using a single-sided PCR approach based on five synthetic oligonucleotides derived from the flanking constant sequence. Double-stranded cDNA was cleaved by a restriction enzyme creating cohesive ends, to which an anchor oligonucleotide was ligated. Since this anchor was complementary to the antisense strand of the known constant region, exclusively the desired ligation product folded into a stem-loop-structure that was enzymatically extended to yield a PCR template, now flanked at both ends by primer binding sites appropriate for nested PCR.


Relationship between Fixed Dental Crowns and Volatile Sulphur Compounds.
The aim of this study was to investigate and compare the level of halitosis in patients with/without fixed crowns and in addition the influence of various crown parameters on halitosis was also explored. In total, 96 subjects (fixed crowns = 52; no crowns = 44) participated in the study. The levels volatile sulphur compounds (VSCs) of hydrogen sulphide (H2S), methyl mercaptan (CH3SH), and dimethyl sulphide (CH3SCH3) were evaluated with breath samples using gas chromatography and used for classification as presence or absence of halitosis. The periodontal clinical parameters for all the participants as well as the crown parameters for participants with fixed crowns were also evaluated. Cross tabulation, Chi-square test, and one-way analysis of variance tests were used for the statistical analysis and comparisons. Breath samples revealed, 50 (52.1%) participants were suffering from halitosis. Out of VSCs, the level of CH3SCH3 (62.5%) was found to be the most prevalent. Significant correlations were observed between the presence of fixed crowns and oral halitosis (p < 0.001). Statistically significant difference in the concentration of H2S and CH3SH (p < 0.001) and no significance for CH3SCH3 (p = 0.075) between patients with/without fixed crowns was found. The presence of halitosis was more prevalent in the subjects with crown parameters (subgingival margin, over-contoured margin, open-crown margin, over-contoured and under-contoured crowns) considered clinically defective/unacceptable (p < 0.05). Presence of fixed dental crowns significantly contributes to the oral halitosis. Dental crowns with defects significantly impair the hygienic conditions and oral microflora resulting in high prevalence of halitosis.


Study on removal of pyrene by Agropyron cristatum L. in pyrene-Ni co-contaminated soil.
Heavy metals and polycyclic aromatic hydrocarbons (PAHs) co-contamination in the soil is widespread. Phytoremediation is often used to remediate co-contaminated soil, but few studies focused on the effects of nickel on the dissipation and uptake of pyrene in phytoremediation. The dissipation of pyrene, the uptake, and distribution of pyrene in Agropyron cristatum L. (A. cristatum) were investigated in this study in the presence of nickel. The pyrene removal rate in single pyrene-contaminated soil with A. cristatum cultivation (48.97%) was the highest, which was higher than that of the co-contamination (47.88%). This was due to the high soil microbial activity and high dissolved organic matter (DOM) contents. In single pyrene-contaminated soil, pyrene was mainly accumulated in the soluble fraction in shoots and on the cell wall in roots of A. cristatuma. Besides, nickel could promote the adsorption of pyrene on the cell wall. Pyrene in A. cristatum could be transported through the apoplast and symplast, and the pyrene contents in the symplast were 2-3 times that of the apoplast. The uptake of pyrene by A. cristatum included both active absorption and passive transportation. Active absorption involved H+ transport and energy conversion processes, and passive transport was associated with water protein channels.


The effect of 2 different diameter cast posts on tooth root fracture resistance in vitro.
Prosthetic treatment frequently involves the restoration of endodontically treated teeth (ETT), which in turn implies that there has been a reduction of the crown due to previous restorative treatment, trauma and/or endodontic manipulations. The prognosis of a restored ETT is very much dependent on pre-endodontic status of the tooth, the quality of the endodontic treatment, the amount remaining tooth structure and the bone support. The aim of this study is to measure fracture resistance of extracted premolar teeth restored with 2 different diameter posts. Extracted premolars were collected and stored in physiologic solution at 5 degrees C. The teeth were examined for fractures by direct and transillumination observation and 40 premolars were accepted for the study. The PC were modelled using the appropriate diameter plastic pattern for the post and Pattern Resin (GC) was used to model the core part of the PC. The PC patterns were invested and cast in cobalt chromium alloy and then cemented using zinc phosphate cement. Fracture resistances of the samples were tested in an "Instron 4301" (Instron Series IX Automated Material Testing System Version 5) with a loading speed of 0.5 mm/min. The data for each sample was recorded graphically. Both groups were analyzed using the t-test (p<0.01) in relationship to the mean value of that group. Post and cores significantly reduce the fracture resistance of the tooth and should be used only to secure retention and resistance form for full coverage crowns. Teeth with a larger diameter post have a reduced fracture resistance than teeth with a smaller diameter.


Association of genetic variants with chronic kidney disease in Japanese individuals.
Although genetic linkage analyses and association studies have implicated several loci and candidate genes in predisposition to chronic kidney disease (CKD), the genes that underlie genetic susceptibility to this condition have remained uncharacterized. The purpose of the present study was to identify genetic variants that confer susceptibility to CKD in Japanese individuals. The study population comprised 5217 Japanese individuals (2955 men, 2262 women), including 778 subjects (480 men, 298 women) with CKD [estimated GFR (eGFR), <50 ml min(-1) 1.73 m(-2)] and 4439 controls (2475 men, 1964 women; eGFR, > or =60 ml min(-1) 1.73 m(-2)). The genotypes for 40 polymorphisms of 32 candidate genes were determined. The chi-square test and multivariable logistic regression analysis with adjustment for covariates revealed that the -219G-->T polymorphism of APOE, the -519A-->G of MMP1, the -866G-->A of UCP2, the -1607/1G-->2G of MMP1, the A-->G (Lys45Glu) of MMP3, the G-->A (Ala163Thr) of AGTR1, the G-->A (Gly670Arg) of PECAM1, and the -55C-->T of UCP3 were significantly (false discovery rate <0.05) associated with CKD. Comparison of allele frequencies of these polymorphisms by the chi-square test between subgroups of CKD and control subjects individually matched for covariates revealed that the -519A-->G of MMP1 and the -866G-->A of UCP2 were significantly (P < 0.05) associated with CKD. MMP1 and UCP2 may be susceptibility loci for CKD in Japanese individuals. Determination of genotypes for these polymorphisms may prove informative for prediction of genetic risk for CKD.


Gut Helminth Infection-Induced Immunotolerance and Consequences for Human Papillomavirus Persistence.
Cervical cancer, a malignancy caused by persistent human papillomavirus (HPV) infection, develops in more than 500,000 women annually. More than 90% of deaths from cervical cancer occur in low- and middle-income countries. A common epidemiological feature of countries with high cervical cancer incidence is a high burden of intestinal helminth infection. The ability of intestinal helminths to trigger immunoregulation, resulting in a "tolerogenic" systemic immune environment, provides fertile soil for the persistence of oncogenic viruses such as HPV. Animal models have shown that intestinal helminth infection permits the persistence of some viruses, however, HPV-specific and human studies are lacking. Large, well-organized trials evaluating the consequences of intestinal helminth infection on the human immune system and HPV persistence may lead to improved strategies for HPV prevention in helminth-endemic regions of the world. Additionally, such studies would offer insight into the specific ways that intestinal helminth infection contributes to immunomodulation, which could identify new therapeutic targets for a range of diseases, from inflammatory disorders to cancer. In this review, we discuss the evidence for helminth-induced systemic and local immune dysregulation, discuss possible mechanisms by which chronic intestinal helminth infection may facilitate HPV persistence, and suggest novel helminth-related interventions that could offer a high leverage (if somewhat unconventional) approach to HPV and cervical cancer control in resource-constrained regions.


Development and Validation of a Claims-Based Model to Predict Levels of Obesity.
We developed and validated a claims-based algorithm that classifies patients into obesity categories. Using Medicare (2007-2017) and Medicaid (2000-2014) claims data linked to two electronic health records (EHR) systems in Boston, Massachusetts, United States, we identified a cohort of patients with an EHR-based BMI measurement. We used regularized regression to select from 137 variables and built generalized linear models to classify patients with BMI≥25, BMI≥30 and BMI≥40. We developed the prediction model using EHR system-1 (training set) and validated it in EHR system-2 (validation set). The cohort contained 123,432 patients in the Medicare and 40,736 patients in the Medicaid population, respetively. The model comprised 97 variables in Medicare and 95 in Medicaid, including BMI-related diagnosis codes, cardiovascular and antidiabetic drugs, and obesity-related comorbidities. The area under the receiver-operating-characteristic curve (AUC) in the validation set was 0.72, 0.76, 0.86 (Medicare) and 0.66, 0.66, 0.70 (Medicaid) for BMI ≥25, BMI ≥30, BMI ≥40, respectively. The positive predictive value was 81.5%, 80.6%, 64.7% (Medicare) and 81.6%, 77.5%, 62.5% (Medicaid), for BMI≥25, BMI≥30, BMI≥40, respectively. The proposed model can identify obesity categories in claims databases when BMI measurements are missing and can be used for confounding adjustment, defining subgroups, or probabilistic bias analysis.


Effect of superchilled storage on shelf life and quality characteristics of M. longissimus lumborum from Chinese Yellow cattle.
The effect of superchilled storage (SC, -4 °C) on shelf life and quality characteristics of M. longissimus lumborum from Chinese Yellow cattle compared with traditional chilling (TC, 2 °C) and frozen storage (-18 °C) was studied. The shelf life of beef steaks held at -4 °C extended to 12 weeks based on the total volatile basic nitrogen (TVB-N) value, which was 2.4 times longer than steaks stored at 2 °C. As the storage time increased, SC samples showed a lower increase of the total aerobic count (TAC), pH and thiobarbituric acid reactive substances (TBARS) values compared to TC samples. Further, L⁎ and a⁎ values of SC samples changed more slowly than that of TC samples. Beef steaks held frozen had a longer shelf life than SC steaks, however, the shear force of frozen steaks remained above 55 N throughout the storage time indicative of toughness. Consequently, SC offers an effective approach for maintaining better shelf life and quality of beef steaks.


Thiazolidinedione derivatives ameliorate albuminuria in streptozotocin-induced diabetic spontaneous hypertensive rat.
Recent reports have shown that thiazolidinediones have preventive effects on urinary albumin excretion in diabetes. However, the mechanism leading to these effects has not yet been elucidated. We studied here the effects of thiazolidinediones on albuminuria and hemodynamic and morphological changes in the kidneys of streptozotocin (STZ)-induced diabetic spontaneous hypertensive rats (SHRs). Diabetes was induced in SHRs by intravenous injection of STZ (50 mg/kg). The diabetic SHRs were divided into the following 3 groups: (1) STZ-SHRs given normal chow (STZ), (2) STZ-SHRs given chow mixed with 0.1% troglitazone (STZ + tro), and (3) STZ-SHRs given chow mixed with 0.001% pioglitazone (STZ + pio). Three groups of nondiabetic SHRs were also investigated: (4) SHR, (5) tro, and (6) pio. We evaluated the urinary albumin excretion rate (AER) every 4 weeks. After 12 weeks of treatment, the animals were killed and renal morphological examinations were performed. Thiazolidinediones did not affect blood pressure or blood glucose levels. Urinary AER were markedly increased in STZ-SHRs. After 12 weeks of treatment with thiazolidinediones, the urinary AER was significantly decreased while creatinine (Cr) clearance was left unchanged. Histologically, the loss of anionic sites of glomerular basement membranes (GBM) evaluated with polyetyleneimine was suppressed significantly in the diabetic SHRs treated with thiazolidinediones. In conclusion, administration of thiazolidinediones in diabetic SHRs decreased the urinary AER and suppressed the loss of anionic sites of GBM without affecting blood pressure, blood glucose levels, or Cr clearance. These results clarify the novel therapeutic action of thiazolidinediones on diabetic nephropathy.


Integrating case topics in medical school curriculum to enhance multiple skill learning: using fetal alcohol spectrum disorders as an exemplary case.
This article describes the use of fetal alcohol spectrum disorders (FASDs) as a theme to connect the learning of basic neurosciences with clinical applications across the age span within a systems-based, integrated curricular structure that emphasizes problem-based learning. In collaboration with the Centers for Disease Control and Prevention (CDC) and the National Organization on Fetal Alcohol Syndrome, the Western Regional Training Center for Fetal Alcohol Exposure at UCLA developed and integrated educational materials on FASDs into the curriculum for first-year medical students. Quantitative and qualitative evaluations suggested materials were effective in enhancing student knowledge and skills related to FASDs, as well as embryology, brain development, substance abuse, developmental psychopathology, and medical ethics. The use of a unifying theme integrating basic science and clinical information and skills is effective for medical student training in the prevention and treatment of common medical problems.


Cornual heterotopic pregnancy and cornual resection after in vitro fertilization/embryo transfer. A report of two cases.
Heterotopic pregnancy occurs in about 1% of pregnancies achieved with assisted reproductive technologies. The incidence of cornual pregnancy is approximately 1% of all ectopics. Two patients became pregnant after treatment with IVF-ET. Both presented during the first trimester with evidence of an acute abdomen and ultrasonographic suspicion for cornual heterotopic pregnancies. The diagnoses were confirmed by laparoscopy, and treatment was undertaken with laparotomy with cornual resection. Both delivered viable infants by cesarean section; the first patient delivered a twin gestation at 28 weeks and the second a singleton pregnancy at 37 weeks. All infants were doing well two months after delivery. Abnormal pregnancies can be detected after IVF-ET with careful follow-up, transvaginal ultrasound studies, serial hCG measurements and pelvic examinations. Cornual heterotopic pregnancies can be successfully treated with cornual resection, especially in cases presenting during the second trimester or when there is clinical evidence of an acute abdomen. All deliveries should be performed by cesarean section at term prior to labor or when tocolysis for premature labor has failed.


A combination of cisplatin-eluting gelatin microspheres and flavopiridol enhances anti-tumour effects in a rabbit VX2 liver tumour model.
The aim of this study was to investigate whether the combination of cisplatin-eluting gelatin microspheres (GMSs) and flavopiridol enhances anti-tumour effects in a rabbit VX2 liver tumour model. Tumour-bearing rabbits (n = 21) were divided into five groups and infused from the proper hepatic artery. Group 1 (n = 5) received cisplatin-eluting GMSs (1 mg kg(-1)) and flavopiridol (3 mg kg(-1)), group 2 (n = 5) cisplatin-eluting GMSs alone (1 mg kg(-1)), Group 3 (n = 5) flavopiridol (3 mg kg(-1)), Group 4 (n = 3) GMSs alone (1 mg kg(-1)), and Group 5 (n = 3) was the control group receiving physiological saline (1 ml kg(-1)). On days 0 and 7 after procedures the liver tumour volume was measured using a horizontal open MRI system and the relative tumour volume growth rates for 7 days after treatment were calculated. On T(1) weighted images, the tumours were visualised as circular, low-intensity areas just below the liver surface. After treatment, the signals remained similar. The relative tumour volume growth rate for 7 days after treatment was 54.2+/-22.4% in Group 1, 134.1+/-40.1% in Group 2,166.7+/-48.1% in Group 3, 341.8+/-8.6% in Group 4 and 583.1+/-46.9% in Group 5; the growth rate was significantly lower in Group 1 than the other groups (p<0.05). We concluded that in our rabbit model of liver tumours the combination of cisplatin-eluting GMSs and flavopiridol was effective.


miR-30a-3p can inhibit the proliferation and promote the differentiation of chicken primary myoblasts.
1. Chicken muscle is an important factor in meat quality and its development is controlled by a complex regulatory network.2. The following study examined the expression of miR-30a-3p in Gushi chicken breast muscle tissue and found that it was differentially expressed at different embryonic stages, reaching a peak in the 14-day-old embryo (E14).3. The effect of miR-30a-3p on chicken primary myoblasts (CPMs) was explored. Results from both cell counting kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) showed that this can inhibit the proliferation of myoblasts, and through cell cycle experiments, the inhibition of myoblast proliferation was found, which may be due to G0/G1 arrest in the cell cycle.4. The effect of miR-30a-3p on the differentiation of myoblasts was studied. The results showed that miR-30a-3p can promote the expression of MYOD, myogenin (MYOG), and myosin heavy chain (MYHC) genes to promote the differentiation of myoblasts. Through MYHC protein immunofluorescence experiments, it was found that miR-30a-3p can effectively increase the area of myotubes.5. Finally, mRNA transcriptome data was analysed, which showed that miR-30a-3p has 51 potential target genes. Among them, forkhead box O3 (FOXO3), ankyrin repeat domain 1 (ANKRD1), and insulin-induced 1 (INSIG1) genes were differentially expressed at different developmental stages and were enriched in Gene Ontology (GO) terms, such as cell differentiation and cellular developmental process. The data showed that tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma (YWHAG), BUB1 mitotic checkpoint serine/threonine kinase (BUB1), and growth arrest and DNA damage-inducible 45 (GADD45) genes were enriched in the cell cycle pathway.6. It can be speculated that miR-30a-3p plays roles through these genes in myoblast development. This research provides information for further improving knowledge of the chicken muscle development regulation network.


Preoperatively Grading Rectal Cancer with the Combination of Intravoxel Incoherent Motions Imaging and Diffusion Kurtosis Imaging.
To combine Intravoxel Incoherent Motions (IVIM) imaging and diffusion kurtosis imaging (DKI) which can aid in the quantification of different biological inspirations including cellularity, vascularity, and microstructural heterogeneity to preoperatively grade rectal cancer. A total of 58 rectal patients were included into this prospective study. MRI was performed with a 3T scanner. Different combinations of IVIM-derived and DKI-derived parameters were performed to grade rectal cancer. Pearson correlation coefficients were applied to evaluate the correlations. Binary logistic regression models were established via integrating different DWI parameters for screening the most sensitive parameter. Receiver operating characteristic analysis was performed for evaluating the diagnostic performance. For individual DWI-derived parameters, all parameters except the pseudodiffusion coefficient displayed the capability of grading rectal cancer (p < 0.05). The better discrimination between high- and low-grade rectal cancer was achieved with the combination of different DWI-derived parameters. Similarly, ROC analysis suggested the combination of D (true diffusion coefficient), f (perfusion fraction), and K app (apparent kurtosis coefficient) yielded the best diagnostic performance (AUC = 0.953, p < 0.001). According to the result of binary logistic analysis, cellularity-related D was the most sensitive predictor (odds ratio: 9.350 ± 2.239) for grading rectal cancer. The combination of IVIM and DKI holds great potential in accurately grading rectal cancer as IVIM and DKI can provide the quantification of different biological inspirations including cellularity, vascularity, and microstructural heterogeneity.


The N-Terminal Domain of Aβ40-Amyloid Fibril: The MOMD Perspective of its Dynamic Structure from NMR Lineshape Analysis.
We have developed the stochastic microscopic-order-macroscopic-disorder (MOMD) approach for elucidating dynamic structures in the solid-state from 2H NMR lineshapes. In MOMD, the probe experiences an effective/collective motional mode. The latter is described by a potential, u, which represents the local spatial-restrictions, a local-motional diffusion tensor, R, and key features of local geometry. Previously we applied MOMD to the well-structured core domain of the 3-fold-symmetric twisted polymorph of the Aβ40-amyloid fibril. Here, we apply it to the N-terminal domain of this fibril. We find that the dynamic structures of the two domains are largely similar but differ in the magnitude and complexity of the key physical parameters. This interpretation differs from previous multisimple-mode (MSM) interpretations of the same experimental data. MSM used for the two domains different combinations of simple motional modes taken to be independent. For the core domain, MOMD and MSM disagree on the character of the dynamic structure. For the N-terminal domain, they even disagree on whether this chain segment is structurally ordered (MOMD finds that it is), and whether it undergoes a phase transition at 260 K where bulklike water located in the fibril matrix freezes (MOMD finds that it does not). These are major differences associated with an important system. While the MOMD description is a physically sound one, there are drawbacks in the MSM descriptions. The results obtained in this study promote our understanding of the dynamic structure of protein aggregates. Thus, they contribute to the effort to pharmacologically control neurodegenerative disorders believed to be caused by such aggregates.


Concurrent preoperative chemoradiotherapy for stage III or IV esophageal squamous carcinoma.
The poor progress of advanced esophageal carcinoma cannot be expected to be improved by surgical treatment alone. We retrospectively examined the results of surgery alone (SA: 39 cases) and of concurrent preoperative chemoradiation therapy (PCRT: 51 cases) for stage III or IV esophageal squamous carcinoma. In the PCRT group, the rate of pathological complete response was 31.4% for the primary lesion and 31.1% for metastatic lymph nodes, which viable cancer cells were not recognized in either region in 25.5% of all cases. In the PCRT group, grade 2 or more toxicity was found in 39 cases of leukopenia, 10 cases of anemia, 7 cases of thrombocytopenia, 11 cases of esophagitis, 4 cases of stomatitis, 2 cases of nausea, 2 cases of diarrhea, 2 cases of liver disfunction and 2 cases of infection. In 2 cases, PCRT was terminated for about 3 weeks because of thrombocytopenia. In the remaining 49 cases, PCRT was administered as scheduled. No statistically significant differences were noted between the PCRT group and the SA group in postoperative complications. There was postoperative recurrence in 16 cases (31.4%) in the PCRT group and 26 cases (66.7%) in the SA group (p=0.008). In stage III, the 5-year survival rate was 58.6% for the PCRT group and 17.2% for the SA group (p=0.022). In stage IV, the survival rate was 0% for the SA group and 16.7% for the PCRT group, showing better results in the latter, although there was no statistically significant difference. Multivariate analysis of prognostic variables revealed that therapeutic method (presence or absence of PCRT) contributed the greatest to the prognosis. These results indicate that PCRT is an effective adjuvant therapy for squamous cell carcinoma.


Children understand communication intuitively, but indirect communication makes them think twice-Evidence from pupillometry and looking patterns.
Interpreting a speaker's communicative acts is a challenge children face permanently in everyday life. In doing so, they seem to understand direct communicative acts more easily than indirect communicative acts. The current study investigated which step in the processing of communicative acts might cause difficulties in understanding indirect communication. To assess the developmental trajectory of this phenomenon, we tested 3- and 5-year-old children (N = 105) using eye tracking and an object-choice task. The children watched videos that showed puppets during their everyday activities (e.g., pet care). For every activity, the puppets were asked which of two objects (e.g., rabbit or dog) they would rather have. The puppets responded either directly (e.g., "I want the rabbit") or indirectly (e.g., "I have a carrot"). Results showed that children chose the object intended by the puppets more often in the direct communication condition than in the indirect communication condition and that 5-year-olds chose correctly more than 3-year-olds. However, even though we found that children's pupil size increased while hearing the utterances, we found no effect for communication type before children had already decided on the correct object during object selection by looking at it. Only after this point-that is, only in children's further fixation patterns and reaction times-did differences for communication type occur. Thus, although children's object-choice performance suggests that indirect communication is harder to understand than direct communication, the cognitive demands during processing of both communication types seem similar. We discuss theoretical implications of these findings for developmental pragmatics in terms of a dual-process account of communication comprehension.


Greater subchondral vBMD at the tibia is observed between 1 and 5 years of anterior cruciate ligament injury.
This study aimed to determine if differences exist in tibial subchondral bone and muscle imbalances between individuals with and without an Anterior Cruciate Ligament (ACL) repair within the past 1 to 5 years (median 3 years). Fifteen individuals (ages 18-23 years) that had a unilateral ACL repair with no contralateral knee injuries and 15 age- and sex-matched controls (no prior knee injuries) were recruited to participate. Subchondral bone was measured using peripheral quantitative computed tomography (pQCT) distal to the tibial plateau. Muscle force, power, and force efficiency were measured using single leg jumps performed on a force platform. Within subject analysis showed a greater subchondral vBMD in the injured versus uninjured legs of cases (278±11 mg/cm3 and 258±6 mg/cm3, respectively, mean±SD, p=0.01). Subchondral vBMD was greater on the injured leg of cases than controls (267±8 mg/cm3 and 237±8 mg/cm3, respectively, marginal mean±SE, p=0.01). No differences were observed between cases and controls for muscle force, power, or force efficiency. Greater subchondral bone mineral density was observed in participants between 1- and 5-years post-op. Given the results of this study and the known long-term effects of ACL injuries, future research must continue to focus on the prevention of these injuries.


Methyl 4-O-beta-D-galactopyranosyl alpha-D-glucopyranoside (methyl alpha-lactoside).
Methyl alpha-lactoside, C13H24O11, (I), is described by glycosidic torsion angles varphi (O5gal-C1gal-O1gal-C4glc) and psi (C1gal-O1gal-C4glc-C5glc), which have values of -93.52 (13) and -144.83 (11) degrees, respectively, where the ring atom numbering conforms to the convention in which C1 is the anomeric C atom and C6 is the exocyclic hydroxymethyl (-CH2OH) C atom in both residues. The linkage geometry is similar to that observed in methyl beta-lactoside methanol solvate, (II), in which varphi is -88.4 (4) degrees and psi is -161.3 (4) degrees. As in (II), an intermolecular O3glc-H...O5gal hydrogen bond is observed in (I). The hydroxymethyl group conformation in both residues is gauche-trans, with torsion angles omegagal (O5gal-C5gal-C6gal-O6gal) and omega(glc) (O5glc-C5glc-C6glc-O6glc) of 69.15 (13) and 72.55 (14) degrees, respectively. The latter torsion angle differs substantially from that found for (II) [-54.6 (2) degrees; gauche-gauche]. Cocrystallization of methanol, which is hydrogen bonded to O6glc in the crystal structure of (II), presumably affects the hydroxymethyl conformation in the Glc residue in (II).


[Genetic engineering of microbial metabolic pathway for production of advanced biodiesel].
Biodiesel is a renewable biofuel and alternative diesel, but the first generation of biodiesel, which has many defects in properties and in production methods, mainly comes from the chemical transesterification of triglyceride from plant oil. With the fast development in the field of synthetic biology and metabolic engineer-ing, the researchers can choose suitable microbes and engineer its metabolic pathways, such as fatty acid bio-synthesis pathway and isoprenoid biosynthesis pathway, to directly produce the second generation of advanced biodiesel---long chain hydrocarbons, which have better properties and quality using the newest biotechnology techniques. In this review, we summarized the research progress about microbial production of advanced bio-diesel and also pointed the deficiencies and future direction in this new field.


Circular YAC vectors containing a small mammalian origin sequence can associate with the nuclear matrix.
Three different mammalian origins of DNA replication, 343, S3, and X24, have been cloned into a 15.8 kb circular yeast vector pYACneo. Subsequent transfection into HeLa cells resulted in the isolation of several stably maintained clones. Two cell lines, C343e2 and CS3e1, were found to have sequences maintained as episomes in long-term culture with a stability per generation of approximately 80%. Both episomes also contain matrix attachment region (MAR) sequences which mediate the binding of DNA to the nuclear skeleton and are thought to play a role in DNA replication. Using high salt extraction of the nucleus and fluorescent in situ hybridization, we were able to demonstrate an association of the 343 episome with the nuclear matrix, most probably through functional MAR sequences that allow an association with the nuclear matrix and associated regions containing essential replication proteins. The presence of functional MARs in small episomal sequences may facilitate the replication and maintenance of transfected DNA as an episome and improve their utility as small episomal constructs, potential microchromosomes.


Is it possible to construct phylogenetic trees using polypeptide hormone sequences?
Because of the high degree of primary sequence conservation in neuropeptides and low molecular weight polypeptide hormones, these polypeptides are not useful for constructing phylogenetic trees based on maximum parsimony analysis. This review focuses on the organization of neuropeptide and polypeptide hormone precursors and discusses strategies for aligning polypeptide precursors for phylogenetic analysis. Examples are provided to support the hypothesis that some neuropeptide and polypeptide precursors and some high molecular weight polypeptide hormones can be used as data sets for resolving deep divergences among vertebrate taxa.


A maximum likelihood method for reconstruction of the evolution of eukaryotic gene structure.
Spliceosomal introns are one of the principal distinctive features of eukaryotes. Nevertheless, different large-scale studies disagree about even the most basic features of their evolution. In order to come up with a more reliable reconstruction of intron evolution, we developed a model that is far more comprehensive than previous ones. This model is rich in parameters, and estimating them accurately is infeasible by straightforward likelihood maximization. Thus, we have developed an expectation-maximization algorithm that allows for efficient maximization. Here, we outline the model and describe the expectation-maximization algorithm in detail. Since the method works with intron presence-absence maps, it is expected to be instrumental for the analysis of the evolution of other binary characters as well.


Prevalence of celiac disease and symptoms in relatives of patients with celiac disease.
We determined the prevalence and clinical features of celiac disease (CD) in family-members (FMs) of a population-based cohort of index cases. We recruited 108 CD index cases: mean age at diagnosis, 23.0 years (range, 1.5-45.2 years); 81 (75%) female. Three-hundred twelve (mean age, 41.6 years; 219 [70%] female) of FMs were analyzed. 153 (49%) were parents, 24 (7.7%) were children, 69 (22.2%) were siblings, 66 (21.1%) were second degree FMs. CD was diagnosed in 63 subjects (20.1%, 21 males and 42 females, mean age 34.24 years, range 2-81 years). Classic, subclinical, and silent forms of CD were recognized in 18 [28.6% (6 siblings, 6 parents, 3 child, 3 second-degree FMs)], in 27 [45.8% (9 siblings, 3 parent, 15 second-degree FMs)], and in 18 [28.6% (6 siblings, 6 parents, 6 second-degree FMs)] cases, respectively. Most of patients suffering from "classical" (18/63 patients, 28.7%) and "subclinical" (27/63 patients, 42.9%) form of CD were older than patients suffering from "silent " CD (18/63 patients, 28.7%) (p=0.01). Most of patients suffering from subclinical disease showed autoimmune diseases (Hashimoto's thyroiditis, and psoriasis), and other atypical symptoms, as gastroesophageal reflux disease (GERD), were also recorded. We found an high-prevalence of CD between CD FMs, and most of them were olygo- or asymptomatic.


Improving visibility of X-ray phase-contrast imaging with Wiener filtering.
To investigate the degrading effects of the physical parameters on the in-line X-ray phase-contrast imaging (XPCi), a simulation tool based on the Fresnel/Kirchhoff diffraction integral was firstly developed with comprehensively considering effects of the source-to-sample (S-S) and sample-to-detector (S-D) distances, the practical characteristics of a polychromatic and finite size source, the point spread function (PSF) of the fluorescent screen and the spatial resolution of the detector on the theoretical phase-contrast pattern. By a comparison between the simulative profile and the experimental one under the commonly-used parameters, an acceptable consistency has been demonstrated in despite of the deviation between the theoretically-predicted contrast (0.188) and the original experimental one (0.12). From the simulations, it is apparently observed that the fine interference pattern has been severely degraded by the finite spatial resolution, and will inevitably be further deteriorated by the system noise in practice. Since the image quality of the X-ray phase-contrast imaging is strongly dependent on the physical parameters of the system, a model-based deblurring procedure to upgrade the image visibility is preferably desired. As a simple restoration way, a Wiener filter was then introduced to offer an optimal tradeoff between the contrast preservation and the noise suppression. Finally, to minimize the deviation resulting from the finite spatial resolution, one-dimensional interpolation was performed by positioning the set square at a tiny angle to the vertical direction. The result after the Wiener-filtering-based deblurring has shown a considerably improved profile visibility: the processed experimental contrast (0.156) increased by 30% as compared to the original one (0.12) in company with the increase in the signal-to-noise ratio (SNR) by 0.9dB. With the trend of the post-filtered experimental contrast to the theoretical one, it could be motivated that higher visibility would be achieved with the introduction of more precise blurring mask and noise spectrum estimation.


Biosynthesis of ferredoxin-NADP+ oxidoreductase. Evidence for the formation of a functional preholoenzyme in the cytoplasmic compartment.
Biosynthesis of ferredoxin-NADP+ reductase in higher plants was investigated in relation with the mechanism of formation of the holoenzyme. The putative precursor of the flavoprotein, obtained after cell-free translation on a wheat germ extract primed with poly(A)-rich mRNA, was able to spontaneously bind free FAD, rendering a functional prereductase. The newly synthesized preholoenzyme showed diaphorase and cytochrome c reductase activities, an apparent molecular mass of 45 kDa, and contained FAD as the only flavin cofactor. It gave a positive reaction towards antisera against mature ferredoxin-NADP+ reductase. On the other hand, intracellular distribution of flavin-synthesizing enzymes indicates that FAD formation occurs in the cytoplasm; that is, in the same compartment as the site of reductase synthesis. On the basis of the preceding data a model is presented for the biosynthesis of the enzyme in vivo, involving conjugation of the apoprotein with FAD in the cytoplasm, followed by transport of the preholoreductase across the chloroplast envelope to reach its final destiny in the thylakoid membrane.


Various macronutrient intakes additively stimulate protein synthesis in liver and muscle of food-deprived chicks.
We investigated the influence of refeeding food-deprived chicks with either protein, carbohydrate, fat or combinations thereof on the rates of liver and muscle protein synthesis. After 2 d of food-deprivation, chicks were given individual or mixed protein, carbohydrate and fat. At 30 min after refeeding, the protein fractional synthesis rate (K(s)) was measured by a large dose injection of L-[2,6-(3)H]phenylalanine. When chicks were food-deprived for 2 d, liver K(s) was 67% lower and muscle fractional synthesis rate was half that of well-fed controls. Upon refeeding starved chicks a complete diet, K(s) in the liver and muscle returned to the level of fed controls within 30 min. When food-deprived chicks were refed protein alone or two of the three macronutrients, liver and muscle K(s) were significantly higher than those in the starved group. There was no effect of refeeding with carbohydrate or fat alone. Plasma glucose concentration was significantly greater than in fed or starved groups in chicks refed the complete diet, carbohydrate or carbohydrate mixed with either protein or fat. Refeeding chicks with the various macronutrients did not affect the plasma insulin or insulin-like growth factor-I concentrations. These results suggest that intakes of individual macronutrients additively increase liver and muscle protein synthesis and that the acute increase in muscle protein synthesis after refeeding chicks diets containing the three macronutrients was mainly regulated by the change in ribosomal efficiency.


Treatment of acute flares of chronic pancreatitis pain with ultrasound guided transversus abdominis plane block: a novel application of a pain management technique in the acute care setting.
The use of transversus abdominis plane (TAP) block to provide either analgesia or anesthesia to the anterior abdominal wall is well described. The technique yields high analgesic effectiveness and is opioid sparing and potentially of long duration with reported analgesia lasting up to 36 hours. When compared to neuraxial analgesia, TAP blocks are associated with a lower incidence of hypotension and motor blockade. TAP blocks are typically described as providing somatic analgesia only without any effect on visceral pain. There may be, however, certain conditions in which TAP blocks can provide effective analgesia in pain of visceral or mixed somatic and visceral origin. We describe two cases in which TAP blockade provided complete control of pain considered to be of visceral origin.


Comparison of standardised milk-based, standardised non-milk based and hospital-based formulations on the anthropometric indices of under-fives with moderate acute malnutrition: A randomised clinical trial.
Moderate acute malnutrition (MAM) causes impaired anthropometry, which can be reversed by supplementary feeding. The present study aimed to compare the effect of a standardised milk-based formulation (SMBF), standardised non-milk based formulation (SNMBF) and hospital-based formulation (HBF) on anthropometric indices of children aged <5 years with MAM. This was a randomised clinical trial during which eligible children aged 6-59 months with MAM received SMBF, SNMBF or HBF over 4 months. They were followed up on a biweekly basis during which their weight, mid upper arm circumference (MUAC) and length/height were measured. The effect of the formulations was determined at the end of the period by the change in their anthropometric indices using 'per protocol' analysis. p < 0.05 was considered statistically significant. There were 157 evaluable participants of whom 54 received the SMBF, 57 received the SNMBF and 46 received the HBF. The overall result showed a significant improvement in the mean weight and MUAC of the children. Subgroup analysis showed a significant improvement in mean weight and MUAC among children aged 6-23 months (p = 0.013) and improvement in MUAC only among those aged 24-59 months (p = 0.03). The formulations significantly improved the mean weight and MUAC of children with MAM.


Peripheral audition of children on the autistic spectrum.
To determine whether the peripheral audition of a group of children comprehensively diagnosed as being on the autistic spectrum was quantitatively different from that of a matched group of typically developing children. Thirty-seven children with autism and an equal number of control participants matched for chronological age within 6 mo were examined by means of behavioral and physiologic measures of auditory function. All participants had normal hearing (thresholds <15 dB HL; 0.25 to 8 kHz) and normal middle ear function by quantitative tympanometry. Conventional behavioral audiometry, a computer-assisted threshold assessment procedure, acoustic middle ear muscle reflex thresholds, and evoked otoacoustic emissions (both transient and distortion product) tests were administered to both groups. No significant differences between children with autism and those developing typically on any behavioral or physiologic measure of peripheral auditory function were found. There was no evidence of intrinsic differences in the peripheral auditory mechanism of children with autism that would account for the auditory processing disorders and sound sensitivity that are commonly reported in this population.


Chemotaxis of Rhizobium spp. to Plant Root Exudates.
Rhizobium spp. show chemotaxis to plant root exudates. Both legumes and non-legume root exudates attract the different rhizobia studied. However, the bacteria show a differential response in that they are attracted to the root exudates of some plants and show no attraction toward others. An example of negative chemotaxis was also observed. The trefoil strain of Rhizobium shows chemotaxis which is qualitatively different from that observed in other bacteria in that simple sugars, di-and trisaccharides, dextrans, and amino acids do not attract this bacterium.


Human Wharton's Jelly Mesenchymal Stem Cells Show Unique Gene Expression Compared with Bone Marrow Mesenchymal Stem Cells Using Single-Cell RNA-Sequencing.
Human Wharton's jelly stem cells (hWJSCs) isolated from the human umbilical cord are a unique population of mesenchymal stem cells (MSCs) with significant clinical utility. Their broad differentiation potential, high rate of proliferation, ready availability from discarded cords, and prolonged maintenance of stemness properties in culture make them an attractive alternative source of MSCs with therapeutic value compared with human bone marrow MSCs (hBMMSCs). We aimed to characterize the differences in gene expression profiles between these two stem cell types using single-cell RNA sequencing (scRNA-Seq) to determine which pathways are involved in conferring hWJSCs with their unique properties. We identified 436 significantly differentially expressed genes between the two cell types, playing roles in processes, including immunomodulation, angiogenesis, wound healing, apoptosis, antitumor activity, and chemotaxis. Expression of immune molecules is particularly high in hWJSCs compared with hBMMSCs. These differences in gene expression may help to explain many of the advantages that hWJSCs have over hBMMSCs for clinical application. Although cell surface protein marker expression indicates that isolated hWJSCs and hBMMSCs are both homogenous populations, using scRNA-Seq we can clearly identify extreme variability in expression levels between individual cells within a certain cell type. If the cells are examined as bulk populations, it is not possible to appreciate that a single cell may be making a major unique contribution to the apparent overall expression level. We demonstrated how the fine tuning of expression within hWJSCs and hBMMSCs may be achieved by expression of molecules with opposing function between two cells. We hypothesize that a greater understanding of these differences in gene expression between the two cell types may aid in the development of new therapies using hWJSCs.


Effectiveness of the Lunch is in the Bag program on communication between the parent, child and child-care provider around fruits, vegetables and whole grain foods: A group-randomized controlled trial.
To evaluate the effectiveness of the parent- and early care education (ECE) center-based Lunch is in the Bag program on communication between parent, child, and their ECE center providers around fruits, vegetables and whole grain foods (FVWG). A total of n=30 ECE center; 577 parent-child dyads participated in this group-randomized controlled trial conducted from 2011 to 2013 in Texas (n=15 ECE center, 327 dyads intervention group; n=15 ECE center, 250 dyads comparison group). Parent-child and parent-ECE center provider communication was measured using a parent-reported survey administered at baseline and end of the five-week intervention period. Multilevel linear regression analysis was used to compare the pre-to-post intervention changes in the parent-child and parent-ECE center provider communication scales. Significance was set at p<0.05. At baseline, parent-child and parent-ECE center provider communication scores were low. There was a significant increase post-intervention in the parent-ECE center provider communication around vegetables (Adjusted β=0.78, 95%CI: 0.13, 1.43, p=0.002), and around fruit (Adjusted β=0.62, 95%CI: 0.04, 0.20, p=0.04) among the parents in the intervention group as compared to those in the comparison group. There were no significant intervention effects on parent-child communication. Lunch is in the Bag had significant positive effects on improving communication between the parents and ECE center providers around FVWG.


Brain abscess caused by Nocardia cyriacigeorgica in two patients with multiple myeloma: novel agents, new spectrum of infections.
Introduction of high-dose chemotherapy and the novel agents including bortezomib, Lenalidomide, and Thalidomide has provided a significant progress in the treatment of multiple myeloma (MM) with an increase in median overall survival up to 6-8 years. However, the advances in myeloma treatment comes at a price with new spectrum of treatment-related infectious complications which should be taken into consideration while treating these patients. We report here two patients with Ig G λ MM presenting with intracerebral mass lesions in the abscence of constitutional symptoms that would suggest an infectious etiology. Both patients had severe hypogammaglobulinemia and lymphopenia, which was attributed to treatment regimens including bortezomib. Intervention The surgical intervention-revealed abscess in both cases caused by Nocardia cyriacigeorgica, a relatively new pathogen which rarely causes infections in humans and also an unexpected pathogen in myeloma patients. Although every aspect of immune system is known to be affected in MM, humoral immune deficiency is the hallmark of the inherent immune defect in this disease. Introduction of the novel agents, bortezomib in particular seems to have changed the characteristics of the immune dysfunction and the spectrum of the opportunistic infections by causing qualitative and quantitative changes in cellular immunity. The new spectrum of infectious agents might not be limited to hepatitis B and herpes zoster. Monitoring lymphopenia and administration of prophylactic antimicrobial agents accordingly could be considered in patients treated with bortezomib.


Carotid intima-media thickness in individuals with and without type 2 diabetes: a reproducibility study.
The use of carotid intima-media thickness (carotid IMT) as a surrogate marker of cardiovascular disease is increasing and the method has now also been applied in several trials investigating patients with type 2 diabetes (T2D). Even though knowledge about methodology is of highest importance in order to make accurate power calculations and analyses of results, no reproducibility studies have been performed in this group of patients. The aim of this study was to quantify the variability of the measurement of carotid IMT in individuals with and without T2D. We used B-mode ultrasound and a computerized software programme (MIA vascular tools) for analysis of carotid IMT. Measurement of carotid IMT in the far wall of the common carotid artery (CCA) was done for 30 patients with T2D and 30 persons without T2D. The examinations were done by two different sonographers and two different readers on two separate days in order to quantify sonographer-, reader-, and day-to-day variability. Comparisons of measurement of carotid IMT in CCA between sonographers (sonographer variability) resulted in limits of agreement (LoA) from -0.18 to 0.13 mm for patients with T2D and -0.12 to 0.10 mm for persons without T2D. This means, that a second scanning of the same person with 95% probability would be within this interval of the first scanning. Comparisons between readers assessing the same scanning (reader variability) resulted in LoA from -0.05 to 0.07 mm and -0.04 to 0.05 mm respectively. LoA of the day-to-day variability was -0.13 to 0.18 mm and -0.09 to 0.18 mm respectively. This corresponds to coefficients of variations (CV) of the sonographer- and day-to-day variability of 10% in patients with T2D and 8% in persons without T2D. The CV of the reader variability was 4% and 3% respectively. Measurement of carotid IMT in the CCA can be determined with good and comparable reproducibility in both patients with T2D and persons without T2D. These findings support the use of carotid IMT in clinical trials with T2D patients and suggest that the numbers of patients needed to detect a given difference will be the same whether the patients have T2D or not.


Delay in the diagnosis of breast cancer: medico-legal implications.
Delay in the diagnosis of breast cancer is an important cause of medical malpractice claims which if trends continue, will threaten healthcare budgets. Most malpractice claims are made by younger women. Delay is most frequently due to the physician failing to be impressed with the clinical findings, or to a false negative mammogram report. Diagnosis of breast cancer is more difficult in younger women, because of the poor sensitivity of diagnostic tests and the high prevalence of benign disease in this age group. Models of tumour growth suggest that the potential to metastasize may be present before the tumour is clinically detectable and that if the growth rate of a given tumour is constant, any clinical delay is a small proportion of the lifespan of the tumour. Patient delay is generally associated with more advanced lesions at presentation, but the effect of delay on survival or what period of delay is significant remains uncertain. Delay in the diagnosis of breast cancer is likely to cause the patient considerable anxiety, especially when the public understands that the aim of mammographic screening is to diagnose breast cancer at an early stage in order to effect a cure. For a plaintiff to successfully claim in court she must prove that she has suffered an injury, and that the injury was the result of negligent medical practice. It is easier to defend a case of delay in diagnosis if the documentation is in order and all the appropriate tests have been performed.


Interval mapping of quantitative trait loci for resistance to late blight [Phytophthora infestans (Mont.) de Bary], height and maturity in a tetraploid population of potato (Solanum tuberosum subsp. tuberosum).
Interval mapping of quantitative trait loci (QTL) for resistance to late blight, height, and maturity was performed on a tetraploid full-sib family of potato comprising 227 clones from a cross between a susceptible parent, 12601ab1, and a resistant cultivar, Stirling, which were of similar height and main crop maturity. Thirty-eight AFLP primer combinations provided 585 informative markers, and 23 SSRs proved useful for identifying linkage groups (LGs). A simplex QTL allele was found on LGV of Stirling close to marker STM3179, which was associated with early maturity, short plants, and susceptibility to blight and explained 54.7, 26.5, 26.3, and 17.5% of the variation for maturity, height, tuber blight, and foliage blight. When the residuals from the regressions of foliage and tuber blight on maturity were analyzed, there was no significant effect of a QTL on LGV, but a duplex QTL allele for resistance was found on LGIV of Stirling, which explained 30.7 and 13.6% of the variation for foliage and tuber blight on an additive model. Partial dominance for resistance explained even more of the variation, up to 37.2% for foliage blight. A major gene for blight resistance in Stirling was also mapped to LGXI.


Salivary pH: A diagnostic biomarker.
Saliva contains a variety of host defense factors. It influences calculus formation and periodontal disease. Different studies have been done to find exact correlation of salivary biomarkers with periodontal disease. With a multitude of biomarkers and complexities in their determination, the salivary pH may be tried to be used as a quick chairside test. The aim of this study was to analyze the pH of saliva and determine its relevance to the severity of periodontal disease. The study population consisted of 300 patients. They were divided into three groups of 100 patients each: Group A had clinically healthy gingiva, Group B who had generalized chronic gingivitis and Group C who had generalized chronic periodontitis. The randomized unstimulated saliva from each patient was collected and pH was tested. Data was analyzed statistically using analysis of variance technique. The salivary pH was more alkaline for patients with generalized chronic gingivitis as compared with the control group (P = 0.001) whereas patients with generalized chronic periodontitis had more acidic pH as compared with the control group (P = 0.001). These results indicate a significant change in the pH depending on the severity of the periodontal condition. The salivary pH shows significant changes and thus relevance to the severity of periodontal disease. Salivary pH may thus be used as a quick chairside diagnostic biomarker.


A vascular cause of painful lumbar transverse syndrome.
Despite typical signs of Leriche syndrome, this patient was misdiagnosed with disk prolapse. Vascular insufficiency, such as aortic occlusion, may underlie a motor-sensory deficit in the lower extremities. Case report. A 67-year-old woman was admitted for cramping pain in the lumbar spine, hips, and legs; diffuse weakness and sensory disturbances of both legs for weeks; and a cold feeling and livid colorization of the legs. Her complaints were attributed to a disk prolapse L5/S1, for which she underwent immediate laminectomy. Postoperatively, symptoms and signs were aggravated, abdominal pain developed, and C-reactive protein and creatinine were elevated. On the fourth postoperative day, femoral pulses were no longer palpable, anuria developed, and computed tomographry angiography showed occlusion of the abdominal aorta distal to the superior mesenteric artery and absent kidney perfusion. The patient died one day later. Postmortem review showed a visible intra-aortic mass on the previous lumbar magnetic resonance image. The differential diagnosis of painful lumbar transverse syndrome should include vascular disease. Misinterpretation of a Leriche syndrome as a disk prolapse has not been reported.


Inferior Macular Damage in Glaucoma: Its Relationship to Retinal Nerve Fiber Layer Defect in Macular Vulnerability Zone.
The purpose of the study was to investigate the prevalence of abnormal thinning of the inferior macular ganglion cell-inner plexiform layer (mGCIPL) in glaucoma and to understand its relationship to abnormal regions of the peripapillary retinal nerve fiber layer (pRNFL), including the macular vulnerability zone (MVZ). We evaluated 186 eyes (186 patients) with glaucoma. An integrated deviation map was merged by superimposition of mGCIPL and pRNFL deviation maps (from a spectral-domain optical coherence tomography) onto RNFL photography as aligned by Photoshop software based on vascular landmarks. The peripapillary area was divided into 2 locations according to a previously suggested schematic model: (1) the MVZ; and (2) the inferoinferior portion. The key findings of the topographic analysis of mGCIPL and pRNFL deviation maps were as follows: (1) 145 of 186 eyes showed inferior mGCIPL loss; (2) if a defect existed in the MVZ of the pRNFL (63 eyes), there was also an inferior mGCIPL defect; (3) however, the other 82 eyes with inferior mGCIPL abnormalities showed an abnormal mGCIPL without a corresponding pRNFL defect in the MVZ. There was no single case of pRNFL defect in the MVZ without inferior mGCIPL loss. However, there were a few cases of inferior mGCIPL loss without pRNFL defect in the MVZ. These findings signify that detection of inferior mGCIPL loss might be earlier than that of pRNFL defect in the MVZ. Therefore, pRNFL analysis of the optical coherence tomography disc cube scan alone is insufficient for detection of early-stage glaucomatous damage.


Beneficial effects of grape seed proanthocyanidin extract on arterial remodeling in spontaneously hypertensive rats via protecting against oxidative stress.
Arterial remodeling is a pathogenic occurrence during hypertension and, in turn, is closely associated with the development and complications of hypertension. Grape seed proanthocyanidin extract (GSPE) has been reported to exhibit a protective effect on cardiovascular disease, however its effect on arterial remodeling remains to be fully elucidated. In the present study, the effects of GSPE on arterial remodeling were analyzed by treating spontaneously hypertensive rats (SHRs) with GSPE (250 mg/kg·day). Arterial remodeling was quantified through morphological methods; thoracic aortas were stained with hematoxylin-eosin or sirius red‑victoria blue. The arterial ultrastructure was imaged using transmission electron microscopy. The content of nitric oxide (NO) and endothelin‑1 (ET‑1) were examined to determine endothelial function. Oxidative stress was assessed by malondialdehyde (MDA) levels and the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). Administration of GSPE markedly alleviated hypertension‑induced arterial remodeling, which was not associated with blood pressure control. ET‑1 production was reduced, while NO production was increased in the GSPE group, which exhibited improved endothelial function. In addition, treatment with GSPE significantly ameliorated oxidative stress by improving SOD and CAT activities and reducing MDA formation. In conclusion, GSPE may attenuate hypertension‑induced arterial remodeling by repressing oxidative stress and is recommended as a potential anti‑arterial remodeling agent for patients with hypertensive vascular diseases.


Loss of troponin-T labelling in endomyocardial biopsies of cardiac transplant patients is associated with increased rejection grading.
Acute cellular rejection after cardiac transplantation surgery is routinely monitored by pathological assessment of haematoxylin and eosin (H&E) histology of endomyocardial biopsies (EMB). Unfortunately, there is considerable variation in the diagnosis of rejection that has been attributed to the subjectivity involved in assessing the degree of (a) inflammatory infiltrate and (b) myocyte damage. In this work, we sought to investigate the potential of high contrast confocal microscopy for numerically assessing inflammatory infiltrate and myocyte damage in EMB histology. Confocal microscopy was used to capture images from EMB fluorescently labelled for nuclei (DAPI), f-actin (phalloidin), troponin-T (anti-body), and extracellular matrix and cell border (wheat germ agglutinin). Images from 28 biopsy procedures were captured. Standard pathological grading of H&E histology identified the following rejection gradings: 6 0R, 16 1R, 6 2R and no 3R. Confocal imaging was able to identify equivalent features of rejection provided by H&E histology but at higher contrast facilitating quantification. Lymphocytic infiltrate was calculated as the ratio of non-myocyte nuclei to total nuclei. This metric was found to be significantly higher in the biopsies from 2R patients compared to both 1R and 0R patients (P < .05). Myocyte damage was quantified as the loss of troponin-T labelling normalised to f-actin labelling. This metric of myocyte damage found significantly lower amounts of troponin-T in the biopsies from 2R patients compared to those with a 0R rejection grading (P < .05). Confocal imaging and simple image processing routines show potential for numerically assessing both inflammatory infiltrate and myocyte damage in endomyocardial biopsy.


Prediction of the main macrocyclic conjugation pathway for porphyrinoids from the ring current distribution.
For some porphyrinoids, such as orangarin and amethyrin, the main route of macrocyclic pi-circulation is different from the main macrocyclic conjugation pathway predicted by porphyrin chemists. Our analytical theory of ring-current diamagnetism allows us to predict the main macrocyclic conjugation pathway from the ring current distribution. We can now interpret macrocyclic aromaticity and macrocyclic circulation consistently within the same theoretical framework.


Characterization of retinal microvasculature and its relations to cognitive function in older people after circuit resistance training.
To characterize the changes of retinal microvascular density and their relations to cognitive function in the healthy older people without known cognitive impairment after an 8-week high-speed circuit resistance training program (HSCT). Twenty cognitively normal older people were recruited and randomly assigned to either the HSCT group or control group (CON). Twelve subjects (age 70.8 ± 5.8 yrs) in the HSCT group trained three times per week for 8 weeks. Eight subjects in the CON group (age 71.8 ± 4.8 yrs) did not perform formal training. Both eyes of each subject were imaged using optical coherence tomography angiography (OCTA) at baseline and at 8-week follow-up. The densities of the retinal vascular network (RVN), superficial vascular plexus (SVP), and deep vascular plexus (DVP) were measured. In addition, their cognitive functions were tested using the NIH toolbox. There were significant increases in pattern comparison processing speed (PAT, P = 0.02) and fluid composite score (FCS, P = 0.005) at the follow-up in the HSCT group. Although the vessel densities did not differ between visits in either group, the variation (i.e., change) in retinal vessel density of SVP was negatively related to the changes of FCS (r = -0.54, P = 0.007) and the List Sorting Working Memory test (r = -0.43, P = 0.039) in the HSCT group. This is the first study to reveal that the individual response of the SVD was related to the improvement in the cognition in cognitively normal older people after HSCT.


Breast-cancer mortality in screened versus unscreened women: Long-term results from a population-based study in Queensland, Australia.
In the context of a mature mammographic screening programme, the aim of this population-based study was to estimate rates of breast-cancer mortality among participants versus non-participants in Queensland, Australia. The Queensland Electoral Roll was used to identify women aged 50-65 in the year 2000 (n = 269,198). Women with a prior history of invasive or in situ breast cancer were excluded (n = 6,848). The study population was then linked to mammography records from BreastScreen Queensland together with the Wesley Breast Screening Clinic (the largest provider of private screening in Queensland) to establish a screened cohort (n = 187,558) and an unscreened cohort (n = 74,792). Cohort members were matched and linked to cancer notifications and deaths through the state-based Queensland Oncology Repository. Differences in breast-cancer mortality between the two cohorts were measured using Cox proportional hazards regression. After 16 years of follow-up, women in the screened cohort showed a 39% reduction in breast-cancer mortality compared to the unscreened cohort (HR = 0.61, 95%CI = 0.55-0.68). Cumulative mortality over the same period was 0.47% and 0.77% in the screened and unscreened cohorts, respectively. This study found a significant reduction in breast-cancer mortality for women who participated in mammographic screening compared to unscreened women. Our findings of a breast-cancer mortality benefit for women who have mammographic screening are in line with other observational studies.


[Mediastinal mass, pulmonary infiltration, and meningitis].
A 42 year-woman suffering from a non-small cell lung cancer, presenting initially as a mediastinal tumor, is hospitalized for fever, headaches and nausea. An aseptic meningitis is diagnosed. The patient died despite the administration of broad spectrum antibiotics and antituberculous agents. The differential diagnoses are presented.


The incidence of smoking and risk factors for smoking initiation in medical faculty students: cohort study.
Medical education requires detailed investigation because it is a period during which the attitudes and behaviors of physicians develop. The purpose of this study was to calculate the yearly smoking prevalence and incidence rates of medical faculty students and to identify the risk factors for adopting smoking behaviour. This is a cohort study in which every student was asked about their smoking habits at the time of first registration to the medical faculty, and was monitored every year. Smoking prevalence, yearly incidence of initiation of smoking and average years of smoking were calculated in analysis. At the time of registration, 21.8% of the students smoked. At the end of six years, males had smoked for an average of 2.6 +/- 3.0 years and females for 1.0 +/- 1.8 years (p < 0.05). Of the 93 medical students who were not smokers at the time of registration, 30 (32.3%) were smokers at the end of the 6 years of the course. The first 3 years of medical education are the most risky period for initiation of smoking. We found that factors such as being male, having a smoking friend in the same environment and having a high trait anxiety score were related to the initiation of smoking. Targeted smoking training should be mandatory for students in the Medical Faculty.