Inhibition of Mung Bean UDP-Glucose: (1-->3)-beta-Glucan Synthase by UDP-Pyridoxal: Evidence for an Active-Site Amino Group.
UDP-pyridoxal competitively inhibits the Ca(2+)-, cellobiose-activated (1-->3)-beta-glucan synthase activity of unfractionated mung bean (Vigna radiata) membranes, with a K(i) of 3.8 +/- 0.7 micromolar, when added simultaneously with the substrate UDP-glucose in brief (3 minute) assays. Preincubation of membranes with UDP-pyridoxal and no UDP-glucose, however, causes progressive reduction of the V(max) of subsequently assayed enzyme and, after equilibrium is reached, 50% inhibition occurs with 0.84 +/- 0.05 micromolar UDP-pyridoxal. This progressive inhibition is reversible provided that the UDP-pyridoxylated membranes are not treated with borohydride, indicating formation of a Schiff's base between the inhibitor and an enzyme amino group. Consistent with this, UDP-pyridoxine is not an inhibitor. The reaction of (1-->3)-beta-glucan synthase with UDP-pyridoxal is stimulated strongly by Ca(2+) and, less effectively, by cellobiose or sucrose, and the enzyme is protected against UDP-pyridoxal by UDP-glucose or by other competitive inhibitors, implying that modification is occurring at the active site. Pyridoxal phosphate is a less potent and less specific inhibitor. Latent (1-->3)-beta-glucan synthase activity inside membrane vesicles can be unmasked and rendered sensitive to UDP-pyridoxal by the addition of digitonin. Treatment of membrane proteins with UDP-[(3)H]pyridoxal and borohydride labels a number of polypeptides but labeling of none of these specifically requires Ca(2+) and sucrose; however, a polypeptide of molecular weight 42,000 is labeled by UDP-[(3)H]pyridoxal in the presence of Mg(2+) and copurifies with (1-->3)-beta-glucan synthase activity.


A retrieval cue for extinction attenuates spontaneous recovery.
Four experiments with rats in an appetitive conditioned magazine entry preparation examined spontaneous recovery after extinction. Spontaneous recovery was obtained 6 days but not 5 hr following extinction; recovery depended on the passage of time but not on the removal of a cue that was featured in extinction or on the reintroduction of early-session cues. A cue featured in extinction attenuated recovery when presented on the test. The attenuation effect depended on the cue's correlation with extinction; a cue featured in conditioning did not attenuate recovery. The extinction cue did not evoke responding on its own, suggesting that it was not a conditioned excitor. Retardation tests and a summation test did not reveal that it was a conditioned inhibitor. The cue might work by retrieving a memory of extinction. Spontaneous recovery thus occurs because the subject fails to retrieve an extinction memory. Other accounts of spontaneous recovery are discussed.


Two new Rinodina lichens from South Korea, with an updated key to the species of Rinodina in the far eastern Asia.
Rinodinasalicis Lee & Hur and Rinodinazeorina Lee & Hur are described as new lichen-forming fungi from forested wetlands or a humid forest in South Korea. Rinodinasalicis is distinguishable from Rinodinaexcrescens Vain., the most similar species, by its olive-gray thallus with smaller areoles without having blastidia, contiguous apothecia, non-pruinose discs, paler disc color, wider ascospores in the Pachysporaria-type II, and the absence of secondary metabolites. Rinodinazeorina differs from Rinodinahypobadia Sheard by areolate and brownish thallus, non-pruinose apothecia, colorless and wider parathecium, narrower paraphyses with non-pigmented and unswollen tips, longer and narrower ascospores with angular to globose lumina, and the absence of pannarin. Molecular analyses employing internal transcribed spacer (ITS) sequences strongly support the two new species to be unique in the genus Rinodina. An updated key is provided to assist in the identification of all 63 taxa in Rinodina of the far eastern Asia.


Feasibility of an intensive outpatient treatment program for posttraumatic stress disorder within the veterans health care administration.
Trauma-focused treatments for posttraumatic stress disorder (PTSD), such as Prolonged Exposure (PE) therapy and Cognitive Processing Therapy (CPT), are effective and supported by various Clinical Practice Guidelines; however, drop-out rates for the treatments are as high as 40% within clinical programs. One promising solution is delivering the evidence-based psychotherapies (EBPs) three or more times per week within an intensive outpatient program (IOP) for PTSD. The present study examined the feasibility and effectiveness of a relatively low-resourced PTSD IOP within a larger PTSD program at the Veterans Healthcare Administration. The intensive program offers two tracks (2 week or 4 week) grounded in the massed delivery of PE and CPT. Over a 12-month period, 351 veterans completed an assessment for PTSD and 172 started within one of the local PTSD programs (e.g., weekly, IOP, or residential). Results of the study demonstrated that the IOP is an acceptable (i.e., 87.3% completion rate) and effective (e.g., PTSD Checklist for Diagnostic and Statistical Manual [DSM-5] [PCL-5] decrease effect size d = 1.80) treatment option. There was also adequate demand for the program (e.g., 37.2% of patients engaged in care with the PTSD programs started the IOP), and the program was implemented with fidelity to the design. Taken together, the results of this study demonstrate that this low-resource IOP model is a promising approach to improve completion rates within the continuum of care for the treatment of PTSD. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Molecular dynamics simulations of a calmodulin-peptide complex in solution.
We have performed an 4-ns MD simulation of calmodulin complexed with a target peptide in explicit water, under realistic conditions of constant temperature and pressure, in the presence of a physiological concentration of counterions and using Ewald summation to avoid truncation of long-range electrostatic forces. During the simulation the system tended to perform small fluctuations around a structure similar to, but somewhat looser than the starting crystal structure. The calmodulin-peptide complex was quite rigid and did not exhibit any large amplitude domain motions such as previously seen in apo- and calcium-bound calmodulin. We analyzed the calmodulin-peptide interactions by calculating buried surface areas, CHARMM interaction energies and continuum model interaction free energies. In the trajectory, the protein surface area buried by contact with the peptide is 1373 A(2) approximately evenly divided between the calmodulin N-terminal, C-terminal and central linker regions. A majority of this buried surface, 803 A(2), comes from nonpolar residues, in contrast to the protein as a whole, for which the surface is made up of mostly polar and charged groups. Our continuum calculations indicate that the largest favorable contribution to peptide binding comes from burial of molecular surface upon complex formation. Electrostatic contributions are favorable but smaller in the trajectory structures, and actually unfavorable for binding in the crystal structure. Since nonpolar groups make up most of buried surface of the protein, our calculations suggest that the hydrophobic effect is the main driving force for binding the helical peptide to calmodulin, consistent with thermodynamic analysis of experimental data. Besides the burial of nonpolar surface area, secondary contributions to peptide binding come from burial of polar surface and electrostatic interactions. In the nonpolar interactions a crucial role is played by the nine methionines of calmodulin. In the electrostatic interactions the negatively charged protein residues and positively charged peptide residues play a dominant role.


Recruitment and maturation of small subsets of luteinizing hormone gonadotropes during the estrous cycle.
Small and medium-sized gonadotropes may enlarge and produce more LH in order to contribute to the proestrous surge. To test this hypothesis, dispersed pituitary cells from cycling female rats were separated by centrifugal elutriation into small, medium, and large fractions and labeled for LH beta antigens or mRNA (by in situ hybridization with a biotinylated oligonucleotide probe complementary to sequences encoding amino acids 28-40). The percentage of cells bearing LH beta mRNA in the pituitary cell population increased from 6 +/- 0.4% in the evening of diestrous day 2 to 16 +/- 0.7% in the morning of estrus (average +/- SEM). Over 80% of these labeled cells were large or small subtypes. The proportion of small gonadotropes labeled with LH beta mRNA declined from 43 +/- 3% at metestrus to 29 +/- 1% on the evening of proestrus as the proportion of medium-sized gonadotropes labeled for LH beta antigens (15 +/- 1%) or mRNA (17 +/- 1%) increased to 25 +/- 2% or 38 +/- 2%, respectively. Because the overall percentage of immunoreactive LH cells did not change after diestrus, small LH cells may have enlarged or increased their density to join the medium-sized pool. During proestrus, the proportion of large immunoreactive LH gonadotropes increased from 41 +/- 2% to 65 +/- 2% (by the morning of estrus) as the proportion of small or medium-sized LH cells declined to 17-18 +/- 1%, suggesting further increases in size or density. These data suggest that small or medium-sized gonadotropes are activated during early diestrus to enlarge and produce LH beta. They contribute to the increased number of cells in medium-sized and large fractions in proestrous or estrous rats. The predominance of the smaller subtypes during metestrus and diestrus suggests that LH gonadotropes may revert to a smaller or lighter subset to await activation during the next cycle.


Novel MR-Guided Radiotherapy Elective Rotation for Radiation Oncology Trainees.
MR-guided adaptive radiation therapy (RT) is emerging as an integral treatment modality for certain applications and is poised to become an exciting opportunity for greater treatment precision and personalization. However, this is still a relatively nascent technology and only a few institutions and programs have access to this technology for clinical use and trainee education. To increase the diversity of elective offerings and improve the understanding of an MR-guided radiotherapy program, we initiated a unique MR-guided radiotherapy elective rotation for radiation oncology residents. During a representative four-week rotation, 21 simulations were completed by the resident on service. A plurality of simulations were for pancreas stereotactic body radiation therapy (SBRT; 48%) and a majority (71%) of simulations were for adaptive treatments. Additionally, 74 adaptive fractions were completed during this month, of which a significant majority (74%) were for pancreas SBRT. Of the non-adaptive fractions, the majority were for prostate SBRT and intensity-modulated radiation therapy (IMRT). Although many programs may offer training in some aspects of MR-guided radiotherapy as trainees rotate through certain disease sites, we hope this may serve as a blueprint to encourage programs with this technology to fully embrace training in essential competencies related to MR-guided radiotherapy. MR-guided radiotherapy has unique challenges that trainees need to understand to deliver treatment safely: geometric uncertainty, MRI to RT isocenter, and uncertainties with voxel size/tracking.


Plantar pressures and gait parameters: a study of foot shape and limb rotations in children.
The most frequent referral diagnosis of childhood to an orthopaedic department is a limb rotational anomaly which manifests itself as either an abnormality of gait or flatfeet. The child is usually asymptomatic, the anxiety being generated in the minds of the parents. One hundred normal children were studied using a Pedobarograph to assess underfoot pressures, and a simple walkway to measure dynamic gait parameters. The results have been correlated with age, and the trends suggest that the pedobarograms may be of use in the prognostication of lower limb rotations. The methods, which are totally noninvasive and can be carried out in the clinic, have the added advantage of reassuring parents that "something is being done."


[Treatment with Pharmachim's Chlophazolin of hypertension and symptomatic hypertonia].
A total of 127 patients with arterial hypertension--64 with symptomatic and 63 with essential, were treated with chlophazolin "Pharmachim" at the Clinic of Therapy of Internal Diseases and Clinical Pharmacology for a period of one year. The drug was used alone in part of the patients and in the rest--in combination with other drugs. Satisfactory effect on the clinical symptoms and the level of blood pressure was attained in all patients treated and in only a small part of them diuretics and beta-blockers were necessary so as to attain better effect in coping with the arterial hypertension. In all patients the drug gave no toxic and allergic reactions, the most frequent adverse affects being the dryness of the mouth and sleepiness.


Effect of calcium intake on urinary oxalate excretion in calcium stone-forming patients.
Dietary calcium lowers the risk of nephrolithiasis due to a decreased absorption of dietary oxalate that is bound by intestinal calcium. The aim of the present study was to evaluate oxaluria in normocalciuric and hypercalciuric lithiasic patients under different calcium intake. Fifty patients (26 females and 24 males, 41 +/- 10 years old), whose 4-day dietary records revealed a regular low calcium intake (<or=500 mg/day), received an oral calcium load (1 g/day) for 7 days. A 24-h urine was obtained before and after load and according to the calciuria under both diets, patients were considered as normocalciuric (NC, N = 15), diet-dependent hypercalciuric (DDHC, N = 9) or diet-independent hypercalciuric (DIHC, N = 26). On regular diet, mean oxaluria was 30 +/- 14 mg/24 h for all patients. The 7-day calcium load induced a significant decrease in mean oxaluria compared to the regular diet in NC and DIHC (20 +/- 12 vs 26 +/- 7 and 27 +/- 18 vs 32 +/- 15 mg/24 h, respectively, P<0.05) but not in DDHC patients (22 +/- 10 vs 23 +/- 5 mg/24 h). The lack of an oxalate decrease among DDHC patients after the calcium load might have been due to higher calcium absorption under higher calcium supply, with a consequent lower amount of calcium left in the intestine to bind with oxalate. These data suggest that a long-lasting regular calcium consumption <500 mg was not associated with high oxaluria and that a subpopulation of hypercalciuric patients who presented a higher intestinal calcium absorption (DDHC) tended to hyperabsorb oxalate as well, so that oxaluria did not change under different calcium intake.


Metagenomic Analysis of 16S Clostridium perfringens Amplicons Corroborates C. perfringens Counts on Select Agar and C. perfringens PCR Analyses of Bacteria in Broiler Farm Litter.
The purpose of this study was twofold-first, to determine whether analysis of bacterial 16S ribosomal RNA (rRNA) in poultry litter corroborated standard Clostridium perfringens counts and PCR assay, and second, to find whether a correlation between 16S rRNA analysis and netB or Tpel toxin PCR intensity with chick mortality existed. At three time points of growout (0, 2, and 4 wk) litter samples were collected from 23 broiler houses representing eight farms during a coccidiosis vaccine control program. DNA extracted from these samples was used for microbiota determination by sequencing the hypervariable V3-V4 region of bacterial 16s rRNA. Obtained sequences were analyzed by QIIME 2 and the Greengenes database for taxonomic composition and relative abundance of C. perfringens in the litter bacterial population. Clostridium perfringens counts on select agar and semiquantitative PCR for C. perfringens were compared with 16S analysis for equivalence testing. Relative abundance of C. perfringens estimated by 16S analysis and semiquantitative PCR for netB and Tpel toxin DNA were analyzed by Pearson linear correlation and statistical equivalence analyses with cumulative chick mortality at 4 and 9 wk growout. When data from all time points were combined, abundance estimates by C. perfringens 16S were statistically equivalent (α = 0.10) to both C. perfringens PCR and C. perfringens counts. Yet, no correlations were observed between any estimate of C. perfringens abundance and cumulative percent chick mortality at 4 or 9 wk growout. However, correlation analyses revealed a significant linear relationship between netB signal at 0 wk (r = 0.55) and 4 wk (r = 0.46) and cumulative mortality at 9 wk growout (P < 0.05). Similarly, abundance of Tpel at 0 and 2 wk showed a linear relationship with cumulative percent mortality at both 4 and 9 wk growout (0.44 ≤ r ≤ 0.54, P < 0.05). No correlations were observed between any other genera or species determined by 16S and cumulative percent chick mortality.


The role of perioperative care in reducing rates of methicillin resistant Staphylococcus aureus.
Methicillin resistant Staphylococcus aureus (MRSA) is defined as any strain of Staphylococcus aureus resistant to beta-lactam antibiotics, including the penicillins and cephalosporins. Over the past ten years the UK has seen a dramatic increase in MRSA prevalence in healthcare facilities and the community, with an estimated 30-50% of healthy adults thought to be colonised with MRSA. Surgical patients are among those at highest risk. With potential sequelae including septicaemia, septic shock, septic arthritis, osteomyelitis, meningitis, pneumonia or endocarditis, it is vital that all care facilities have up to date evidence-based guidelines to tackle this problem. The purpose of this review is to highlight the current evidence supporting some of the key perioperative measures which may be implemented in preventing MRSA.


Effects of telephone versus face-to-face interview modes on reports of alcohol consumption.
In order to assess the effects of survey modality on alcohol consumption estimates, data from two surveys using different interview modes (face-to-face and telephone) were compared on several alcohol measures. Face-to-face survey data were drawn from the 1990 National Alcohol Survey, while the telephone data came from the 1990 Warning Labels Survey. Both surveys used a probability sampling of the US adult general population in the 48 contiguous states. Measures of alcohol use derived from an identical "graduated frequencies" series included estimates of any drinking in the past 12 months, overall volume, and heavy (5+) drinking days. Abstention rates did not differ by survey mode, nor did distributions of alcohol consumption by volume and reported frequency of drinking five or more drinks in a day. Multiple regression models including demographic-mode interaction terms were used to examine how mode effects might differ across demographic subgroups. Lower income respondents were under-represented in the telephone sample, and were associated with lower reports of volume and 5+ days, compared to respondents in the face-to-face mode. The results suggest that although there are few differences in alcohol consumption estimates by interview mode, telephone samples may need to be supplemented or estimates adjusted by income level in order to attain equivalent results.


Determination of soluble interleukin-2 receptor in human seminal plasma.
Following lymphocyte activation a soluble form of TAC antigen is released. This soluble molecule (soluble interleukin-2 receptor, SIL-2R) seems to corresponds to a truncated extracellular part of the membrane-bound TAC antigen, being smaller than its cellular counterpart. SIL-2R was determined and correlated with PMN elastase levels in the seminal plasma of 79 adult men having different concentrations of PMN elastase (0-700 micrograms/L). The normal level of SIL-2R was detected in the seminal plasma of 15 healthy men. The mean +/- SEM was 101 +/- 29 units/mL. The relation between PMN elastase in human seminal plasma as an index for the state of lymphocyte activity and the sperm motility is also investigated.


Light and stomatal metabolism : I. Possible involvement of light modulation of enzymes in stomatal movement.
New evidence is provided regarding the direct effect of light on stomatal opening in the epidermis of the pea (Pisum sativum L. var Little Marvel) leaf. Light modulates the activity of a number of key enzymes involved in stomatal metabolism. When isolated epidermal strips are illuminated, phosphoenolpyruvate carboxylase, NADP-malate dehydrogenase, and NADP-isocitrate dehydrogenase are activated; and aspartate aminotransferase is inactivated. Sulfhydryl compounds, dithiothreitol and glutathione, enhance stomatal opening in epidermal strips both in light or darkness while the sulfhydryl reagent N-ethylmaleimide inhibits, indicating the possible involvement of sulfhydryl groups in stomatal movements. Further, light treatment increases measureable thiol levels in the epidermis about 3-fold. These results suggest that light modulation of enzymes in the epidermis may play a significant role in the mechanism of stomatal movement.


Noninvasive positive pressure ventilation in hospital setting.
Noninvasive positive pressure ventilation (NPPV) refers to the delivery of mechanical ventilation to the lungs using techniques that do not require an endotracheal intubation. In the past decade NPPV has gained wide acceptance and is now used more frequently after development of portable ventilators, new modes of ventilation and other equipments. This article will provide a comprehensive overview of the current stage of NPPV in acute and chronic settings. It will appraise the evidence based efficacy of NPPV in patients who presented with acute exacerbation of chronic hypercapneic respiratory failure. The main focus of discussion in this article is to provide detailed knowledge regarding choosing appropriate ventilators and interfaces, selecting appropriate patients and initiating NPPV and their weaning.


Radiation dosimetry and efficacy of an 89Zr/225Ac-labeled humanized anti-MUC5AC antibody.
Theranostic applications are currently difficult to achieve owing to the limited evaluation of suitable chelators for therapeutic nuclides, such as 225Ac and 227Th. With a focus on targeted α therapy and theranostics using human IgG as a drug-delivery system (i.e., combining highly cytotoxic α-particle emitter radiation with efficient tumor targeting), we developed a recombinant humanized Nd2 (hNd2) as an anti-MUC5AC antibody since MUC5AC is highly expressed in patients with pancreatic cancer. Therefore, we aimed to evaluate the performance of 89Zr- (for diagnosis) and 225Ac- (for therapy) labeling of these antibodies using well-controlled radioisotope (RI)-labeling technology in pancreatic cancer mouse models. 89Zr-labeled hNd2 (NMK89) and 225Ac-labeled hNd2 (NMT25) were manufactured by chemical conjugation using affinity peptides. A binding assay and the evaluation of plasma stability were performed in vitro to confirm the properties of NMK89 and NMT25. In vivo, we evaluated biodistribution, positron emission tomography (PET)/computed tomography (CT) imaging, antitumor effects, and toxicity. Moreover, the exposure dose in humans was estimated based on the biodistribution evaluation in normal mice. NMK89 and NMT25 showed binding specificity to MUC5AC and stability with radiochemical purity ≥90% in mice and human plasma following incubation for 168 h. NMK89 showed high accumulation in tumors and low non-specific accumulation in normal tissues. The antitumor effect of NMT25 was dose-dependent and significantly suppressed tumor growth in the NMT25 treatment groups compared with the control group (p < 0.05). NMK89 and NMT25 showed similar pharmacokinetics and biodistribution characteristics. Additionally, the human estimated exposure dose of NMK89 and NMT25 was confirmed, and the effective dose of NMK89 and NMT25 was 0.33 mSv/MBq and 177.5 mSv/MBq, respectively. NMK89 showed specific accumulation in the MUC5AC-expressing tumors, while NMT25 showed strong antitumor effects. These results suggest NMK89 and NMT25 as promising theranostic agents for pancreatic cancer.


Seasonal affective disorder: response to light as measured by electroencephalogram, melatonin suppression, and cerebral blood flow.
This study was designed to test the hypothesis that patients with SAD have significantly different physiological responses to light than healthy age- and sex-matched controls. We studied retinal contrast sensitivity, visual evoked EEG responses, and melatonin suppression by, and cerebral blood flow response to, full-spectrum artificial daylight. There was no significant difference between 10 patients and 11 controls in retinal contrast sensitivity, or amplitude or latency of N2, P2, P100 or P300 on EEG. We compared melatonin suppression in 12 SAD patients and 12 controls. During exposure to 500 lux and 1500 lux artificial daylight both the SAD patients and controls had a significant melatonin percentage suppression; however, the percentage suppression did not differ significantly between the SAD patients and the controls. In addition, we carried out a small pilot study into the effect of light on cerebral blood flow in four SAD patients and four controls. Before exposure to 1500 lux artificial daylight there was no significant difference between patients and controls in global, regional or cerebral hemispheric blood flow. After light exposure the SAD patients and controls had a significantly different percentage change in cerebral blood flow. We suggest that patients with SAD do not have significantly physiological responses to light than controls, except perhaps in cerebral blood flow. Furthermore, mechanisms other than supersensitivity of melatonin suppression must explain both the pathophysiology of the disorder and its response to treatment with light.


A survey of obstetricians willingness to practice collaboratively with midwives in Taiwan.
This study was designed to investigate obstetricians willingness to practice collaboratively with midwives in Taiwan. Systematic random sampling was used to access the 500 participants from the 2,256 registered members of the Association of Obstetrics and Gynecology of the Republic of China. A questionnaire and four open-ended questions were designed to examine obstetricians willingness to work collaboratively with midwives and other related factors. A total of 78 physicians returned the questionnaires, providing a response rate of 15.6%. Thirty-six (46.2%) of subjects worked as private obstetricians, with a mean age of 47.1 years. About 79.5% (n = 62) had over 10 years of experiences in their role. Fifty percent (n = 39) worked in areas with birth rats less than 50 infants per month. The findings of the current study demonstrate, regarding the seven midwifery practice items on the questionnaire, that all 78 obstetricians were unwilling to work collaboratively with midwives. However, results showed that if midwifery education were to be advanced to college level, the degree of willingness to work collaboratively with midwives improved significantly (t > 1.96, p <.05). Furthermore, 56.4% (n = 44) obstetricians would then agree to work collaboratively with midwives. However, 43.6% (n = 34) were unwilling to accept midwives as independent practitioners. Reasons included: unwillingness to share risks, worry about the incapability of midwives, worry that it would impair the professional image of physicians, and unwillingness to share interests. The authors conclude that advancing and enhancing midwifery education in Taiwan should be the first step to negotiate in order to raise the profile of midwives specifically and the midwifery profession generally. Ultimately, such a strategy would improve the quality of care provided to women and their infants and consequently improve the health and social well-being of present and future generations.


Evaluating Mechanical Bowel Preparation Prior to Total Laparoscopic Hysterectomy.
Mechanical bowel preparation (MBP) has been used prior to total laparoscopic hysterectomy (TLH), but evidence for its use is lacking. Our study seeks to assess whether or not completion of preoperative MBP prior to TLH improves visualization of the surgical field, bowel handling, or overall ease of the operation. Women aged 18-65 years undergoing TLH for benign indications at a level 1 trauma center were randomized to a bowel preparation (BP; n = 39) or non-bowel preparation (NP; n = 39) regimen. After each operation, the surgeon completed a survey about intraoperative visualization of the surgical field, bowel handling, and the overall ease of the operation. The surgeon was also asked whether or not he thought the patient had completed MBP. The patient completed a survey about pre- and postoperative gastrointestinal discomfort. The surgeon was blinded to whether MBP was completed before the operation. There was no difference in intraoperative visualization, bowel handling, or overall ease of the operation between the BP and NP groups. Comfort levels before and after surgery were not significantly different between the two groups. The surgeon was able to correctly predict whether the patient performed MBP in 59% of cases. The routine use of MBP before TLH does not improve intraoperative visualization, bowel handling, or overall ease of performing the procedure. It also has no significant effect on patient comfort levels. MBP is not indicated before TLH for benign indications.


A myogenic switch. Muscle development.
Experiments manipulating the level of the basic helix-loop-helix transcription factor Twist in the Drosophila embryo have revealed a novel role for this protein in a 'myogenic switch' during early development.


Upper airway compression after arthroscopy of the temporomandibular joint.
An unusual complication is presented following a temporomandibular arthroscopy carried out under general anaesthesia. Severe cervicofacial oedema occurred immediately after surgery which required prolonged endotracheal intubation. Retrospective analysis revealed a massive fluid escape in the surrounding tissues leading to laryngeal oedema.


Macro- and microcirculation patterns of intrahepatic blood flow changes in patients with hereditary hemorrhagic telangiectasia.
To evaluated vascular dynamic processes in the liver of hereditary hemorrhagic telangiectasia (HHT) patients by ultrasound (US) considering quantitative analytic methods. The imaging features on US and contrast-enhanced ultrasound (CEUS) in 18 patients diagnosed with HHT were retrospectively analyzed. Regarding CEUS, real-time contrast harmonic imaging and sulfur hexafluoride-filled microbubbles were used. HVaMs were identified in all 18 patients. By US, the two major Caselitz criteria could be detected in 55.6% patients. "Color spots" were detected in 72.2% of the cases. Respecting sonographic grading criteria by Buscarini, grade 3 could be demonstrated most frequent (40%). By CEUS, all the patients showed quick and early hyperenhancement during the arterial phase. Significant lowest time to peak (TTP) and highest area under the curve (AUC) values were identified in the hepatic artery (TTP: 69.8%; AUC: 100%) and highest TTP and lowest AUC in the hepatic parenchyma and the portal vein. For the first time we analyzed CEUS findings of a group of HHT patients regarding macro- and microcirculation. Our data demonstrate significant differences in TTP and AUC values in the four selected regions: hepatic artery, shunt region, portal vein and hepatic parenchyma.


Association between stroke and atrial septal aneurysm assessed by transesophageal echocardiography in a cardiologic population.
Atrial septal aneurysm (ASA) is now recognized as a source of emboli. Its prevalence in a general population remains controversial. We assessed, in a cardiologic population, the prevalence of ASA, the association with cerebrovascular events, the role of associated interatrial shunting and age. Four hundred and ninety-four consecutive patients were referred for transesophageal echocardiography with contrast. The prevalence of ASA in two groups, with (A) and without (B) cerebrovascular events were compared. In group A, we studied the prevalence of ASA according to the clinical presentation (stroke, TIA and peripheral emboli in limbs). An ASA was found in 38 patients (8%). The prevalence of ASA was higher in group A (16%) than in group B (4%) (p < 10(-5)). Prevalence of ASA was not significantly different in stroke, TIA and peripheral emboli subgroups. There was no difference in prevalence of ASA in stroke or TIA subgroups according whether age was < 55 years or > or = 55 years. Prevalence of all types of vascular events was increased when ASA was associated with an interatrial shunt. Our results support the assumption that ASA is a potential source of cerebrovascular events, whatever the clinical presentation or age. Presence of interatrial shunt increases the risk of stroke in subjects with ASA.


Colorectal cancer. Recent developments and continuing controversies.
In the last 2 years, much progress has been made in colorectal cancer research. Many of the findings, especially those involving adjuvant therapy, have important clinical applications. For example, fluorouracil (5-FU) (Adrucil) combined with levamisole hydrochloride (Ergamisol) is now recommended as adjuvant therapy for patients with Dukes' stage C (III) disease. Some aspects of colorectal cancer remain controversial, particularly screening recommendations and monitoring of carcinoembryonic antigen levels.


Innovative designs in behavioural trials.
Clinical trials that compare pharmacological and behavioural treatments require extra attention to design on the part of the investigators. Many of the standard control mechanisms for comparison of active drug to placebo and behavioural therapy to control therapy create problems when the two types of interventions are combined. The most important of these problems is the introduction of non-specific effects introduced by behavioural therapists and physicians that can bias the study. Solutions to these problems require procedures that are common to both types of studies and the introduction of more complex statistical designs to adequately control the proposed comparisons. It may also be necessary to have a robust statistical method to address informative censoring since patients assigned to behavioural therapy may drop out of the study for different reasons than patients who drop out of a pharmacological trial. In this paper we use the design of the Raynaud's Treatment Study to demonstrate methods that can be used to control for non-specific effects and differential drop-out from the study.


Perovzalates: a family of perovskite-related oxalates.
A family of hybrid Perovskite-oxalates ("Perovzalates") of general composition AILi3MII(C2O4)3 (A = K+, Rb+, Cs+; M = Fe2+, Co2+, Ni2+) are presented. All eight new compounds are isostructural with the previously reported examples NH4Li3Fe(C2O4)3 and KLi3Fe(C2O4)3, crystallising in the rhombohedral space group R3[combining macron]c, with a∼11.3-11.6 Å, c∼14.8-15.2 Å. In contrast to other families of "hybrid perovskites" such as the formates, these compounds can be regarded as closer structural relatives to inorganic (oxide) perovskites, in the sense that they contain direct linkages of the octahedral sites via bridging oxygen atoms (of the oxalate groups). It is of note, therefore, that monoatomic cations as large as Cs+ can be incorporated into the perovskite-like A sites of this structure type, which is not feasible in traditional ABO3 perovskites; indeed CsLi3Ni(C2O4)3 appears to exhibit the 'mostly tightly bound' 12-coordinate Cs+ ion in an oxide environment, according to a bond valence analysis.


Cherubism: report of three cases.
Cherubism is a very rare, inherited autosomal-dominant disease, affecting mostly the mandible. Usually the chief complaint on examination is painless bilateral swelling involving the angles of the mandible. On palpation, the lesions are hard and the jaw is expanded; often there is displacement of erupted teeth.


Relationship of urinary polyamines to tumor activity and tumor volume in patients.
Serially obtained urinary polyamine levels were determined for 192 patients during a specified time period. The number of patient urine samples totaled 938. The patients had tumors of either the breast, stomach, prostate, or female genital tract, or metastatic carcinomas of unknown origin. Tumor activity and tumor volume, along with other clinical information, were also recorded during the time period. Possible associations between tumor activity and tumor volume on one hand, and polyamine levels on the other hand, were explored via different statistical analyses. For each tumor type, statistically significant group differences were found in polyamine levels between patients with nonactive tumors and patients with active large tumors. Predictive values of polyamine assays for change in disease activity and stability in disease nonactivity for tumors of the breast, female genital tract, and prostate were also computed. For breast tumors, these predictive values do not support the clinical utility of the use of polyamine levels to monitor disease states. For tumors of the female genital tract and prostate, these predictive values yield an indeterminant conclusion.


Leader Extraversion as a Boundary Condition in the Relationship between Transformational Leadership, Vitality, and Job Improvement.
We examine the relationship between transformational leadership and job improvement behaviors by considering the moderating effect of leader extraversion and the mediating role of employee vitality. Multi-level path analysis on data from 101 leaders and 619 subordinates provided support to the moderating effect of leader extraversion, such that the relationship between transformational leadership and employee vitality is stronger when the level of leader extraversion is high. Moreover, a moderated mediation procedure showed that the indirect effect of transformational leadership on job improvement via employee vitality was conditional to the level of leader extraversion. We highlight the original contributions of these findings by discussing the moderating role of leader extraversion as an understudied theoretical alternative to its already well-explored role as an antecedent to leadership behaviors. On a practical level, our results indicate that organizations should consider not only what leaders do (transformational leadership behaviors) but also how these behaviors are contextualized by leaders' typical approach (extraversion) to instill a maximum of positive emotion such as vitality in employees.


Benign metastatic mixed tumours or unrecognized salivary carcinomas?
'Benign metastasizing mixed tumours' are enigmatic lesions of the parotid gland. The authors, through the illustrations of a case and review of the literature, conclude that the tumours are unrecognized and currently unclassified malignancies.


BOLD fMRI effects of transcutaneous vagus nerve stimulation in patients with chronic tinnitus.
Vagus nerve stimulation (VNS) is a neuromodulation method used for treatment of epilepsy and depression. Transcutaneous VNS (tVNS) has been gaining popularity as a noninvasive alternative to VNS. Previous tVNS neuroimaging studies revealed brain (de)activation patterns that involved multiple areas implicated in tinnitus generation and perception. In this study, functional magnetic resonance imaging (fMRI) was used to explore the effects of tVNS on brain activity in patients with tinnitus. Thirty-six patients with chronic tinnitus received tVNS to the inner tragus, cymba conchae, and earlobe (sham stimulation). The locus coeruleus and nucleus of the solitary tract in the brainstem were activated in response to stimulation of both locations compared with the sham stimulation. The cochlear nuclei were also activated, which was not observed in healthy subjects with normal hearing. Multiple auditory and limbic structures, as well as other brain areas associated with generation and perception of tinnitus, were deactivated by tVNS, particularly the parahippocampal gyrus, which was recently speculated to cause tinnitus in hearing-impaired patients. tVNS via the inner tragus or cymba conchae suppressed neural activity in the auditory, limbic, and other tinnitus-related non-auditory areas through auditory and vagal ascending pathways in tinnitus patients. The results from this study are discussed in the context of several existing models of tinnitus. They indicate that the mechanism of action of tVNS might be involved in multiple brain areas responsible for the generation of tinnitus, tinnitus-related emotional annoyance, and their mutual reinforcement.


Correction of discrete subaortic stenosis with abnormal chordae tendineae.
The case of a 52-year-old woman with subvalvular aortic stenosis and aortic regurgitation is presented. Mitral regurgitation was associated, due to insertion of two abnormal chordae tendineae at the apex of the anterior papillary muscle and at the free border of the subvalvular membranous annulus. This abnormality displaced the anterior papillary muscle, thus applying a traction at the mitral leaflet. The patient was operated on through a valve-sparing approach, in which the discrete subaortic stenosis was removed through aortotomy and the ectopic chordae were excised. Suture mitral annuloplasty completed the procedure. Aortic and mitral insufficiency almost disappeared at follow-up. From the examination of this case and from a review of pertinent literature it emerges that in event of similar complex congenital abnormalities without intrinsic valve disease, a conservative approach should be chosen so that valve replacement can be avoided.


Transformation of biodegradable polyesters into cyclic oligomers under continuous flow using an enzyme-packed column.
The enzymatic degradation of typical chemically synthesized biodegradable plastics, such as poly(butylene adipate) and poly(epsilon-caprolactone), to a repolymerizable cyclic oligomer under continuous flow using an enzyme column was studied, directed towards green chemical recycling. It was confirmed that both polymers were quantitatively transformed into the corresponding cyclic oligomers by passage through the column packed with immobilized lipase from Candida antarctica (Novozym 435) at 40 degrees C using a toluene solution. Compared to the batch treatment in a flask, a short reaction time and a low reaction temperature occurred for complete transformations of the polyesters by continuous flow through the enzyme column. The degradation activity of the enzyme column was maintained for at least six months at 40 degrees C. Conceptual scheme of the continuous degradation equipment using the enzyme column.


Virus-enabled silicon anode for lithium-ion batteries.
A novel three-dimensional Tobacco mosaic virus assembled silicon anode is reported. This electrode combines genetically modified virus templates for the production of high aspect ratio nanofeatured surfaces with electroless deposition to produce an integrated nickel current collector followed by physical vapor deposition of a silicon layer to form a high capacity silicon anode. This composite silicon anode produced high capacities (3300 mAh/g), excellent charge-discharge cycling stability (0.20% loss per cycle at 1C), and consistent rate capabilities (46.4% at 4C) between 0 and 1.5 V. The biological templated nanocomposite electrode architecture displays a nearly 10-fold increase in capacity over currently available graphite anodes with remarkable cycling stability.


Equivalent Dose Rate 1 Meter from Neuroendocrine Tumor Patients Exiting the Nuclear Medicine Department After Undergoing Imaging.
123I-metaiodobenzylguanidine (MIBG) and 111In-pentetrotide SPECT have been used for functional imaging of neuroendocrine tumors (NETs) for the last 2 decades. More recently, PET/CT imaging with 18F-FDG, 18F-fluorodihydroxyphenylalanine (FDOPA), and 68Ga somatostatin-receptor ligands in NETs has been expanding. A literature search could find no direct measurements of the dose rate from NET patients exiting the nuclear medicine department after undergoing PET/CT with 18F-FDOPA or 68Ga-DOTATOC, a somatostatin analog. Methods: We measured the dose rates from 93 NET patients on leaving the department after undergoing PET/CT or SPECT/CT in our centers. In total, 103 paired measurements of equivalent dose rate at 1 m (EDR-1m) from the sternum and urinary bladder were obtained. The detector faced the sternum or bladder and was 1 m away from and directly in front of the patient. The practice for exiting the department differed according to whether the patient had been referred for PET/CT or for SPECT/CT. PET/CT patients were discharged after imaging, whereas SPECT/CT patients left the department earlier, just after radiopharmaceutical injection. Results: The median administered activity was 122 MBq in 53 68Ga-DOTATOC PET/CT studies, 198 MBq in 15 18F-FDOPA PET/CT studies, and 176 MBq in 13 18F-FDG PET/CT studies. The corresponding median EDR-1m was 4.8, 9.5, and 8.8 μSv/h, respectively, facing the sternum, and 5.1, 10.1, and 9.5 μSv/h, respectively, facing the bladder. The median administered activity was 170 MBq in 12 111In-pentetreotide SPECT/CT studies and 186 MBq in 10 123I-MIBG SPECT/CT studies. The corresponding median EDR-1m was 9.4, and 4.9 μSv/h, respectively, at the level of the sternum, and 9.3 and 4.7 μSv/h, respectively, at the level of the bladder. The EDR-1m was less than 20 μSv/h in all patients. Thus, when exiting the nuclear medicine department, the NET patients injected with 68Ga-DOTATOC or 123I MIBG emitted an average EDR-1m roughly half that of patients injected with other radiopharmaceuticals. This finding is a complementary argument for replacing SPECT by PET somatostatin-receptor imaging. Conclusion: Our current practice of allowing patients to exit after PET/CT imaging or just after SPECT radiopharmaceutical injection appears to be safe from a radiation protection point of view. Restrictive advice is unnecessary for NET patients being discharged from the department.


Plasma-enhanced chemical vapor deposition of low-loss SiON optical waveguides at 15-microm wavelength.
Good optical-quality SiON layers deposited upon a SiO(2) buffer layer placed upon silicon wafers have been obtained by using plasma-enhanced chemical vapor deposition from SiH(4), NH(3), and N(2)O. Optical planar waveguides with a thickness of 5 microm and a refractive index of 1.470 have been deposited and investigated in the wavelength region of 1.3-1.6 microm. Three absorption bands at 1.40, 1.48, and 1.54 microm have been detected and interpreted as Si-OH, N-H, and Si-H vibrational modes, respectively. Absorption losses of 3.8 dB/cm at 1.4 microm and 3.2 dB/cm at 1.51 microm have been measured. A mild annealing at approximately 800 degrees C completely removes the band at 1.40 microm, whereas strong reduction of absorption at 1.51 microm requires 3 h of annealing at 1100 degrees C. As a result, propagation losses of 0.36 to 0.54 dB/cm have been measured at 1.54-microm wavelength.


Silent diabetic nephropathy.
To examine the risk of renal events in patients with biopsy-proven diabetic nephropathy (DN) and its possible associated factors. Clinical and histological data of 60 patients diagnosed with diabetic nephropathy were retrospectively collected. Patients with evidence or suspicion of other nephropathies were excluded from the study. The final event was defined as renal replacement therapy (RRT) initiation or progression of chronic kidney disease (CKD), according to the KDIGO 2012 definition of a decrease in CKD category and a decrease in GFR of 25% or more. A total of 45 patients with a follow-up of at least 3 mo were included. Most of the patients presented type 2 DM, with a mean age of 58.3 years old. The time of evolution of DM was 9.6 ± 7.8 years, although in 13 patients, it was less than 5 years. A total of 62% of patients reached the final event in a median period of 3.4 years (95%CI: 2.1-4.7), with 21 of them requiring dialysis. The factors that were independently associated with renal survival were estimated glomerular filtration rate (eGFR) at the time of biopsy, cardiovascular disease (CVD) history and HbA1c less than 7%. Therefore, for each 10 mL/min per 1.73 m(2) reduction in eGFR, we obtained a DN progression risk of HR = 2 (1.3-3.0) (P = 0.001); patients with CVD were at greater risk for DN progression (HR = 2.8, 1.1-7.1, P = 0.032), and CKD patients with HbA1c < 7% demonstrated greater renal risk than patients with HbA1c ≥ 7%, with an HR of 2.9 (1.0-8.4) (P = 0.054). A past history of CVD is a risk factor for DN progression. Levels of HbA1c less than 7% could favor an eGFR decrease in these patients.


CD4+ and CD8+ T lymphocytes both contribute to acquired immunity to blood-stage Plasmodium chabaudi AS.
In the present study, the contribution of CD4+ and CD8+ T lymphocytes to acquired immunity to blood-stage infection with the murine malaria species Plasmodium chabaudi AS was investigated. C57BL/6 mice, which are genetically resistant to infection with this hemoprotozoan parasite and exhibit a transient course of infection, were treated intraperitoneally with monoclonal antibodies to T-cell epitopes, either anti-Thy-1, anti-CD4, or anti-CD8. After intraperitoneal infection with 10(6) parasitized erythrocytes, control C57BL/6 mice exhibited a peak parasitemia on day 9 of approximately 35% parasitized erythrocytes and eliminated the infection within 4 weeks. Mice depleted of Thy-1+ or CD4+ T cells had significantly higher parasitemias on day 7 as well as significantly higher peak parasitemias. These mice were unable to control the infection and developed a persistent, high parasitemia that fluctuated between 40 and 60% until the experiment was terminated on day 56 postinfection. Depletion of CD8+ T lymphocytes was found to have no effect on the early course of parasitemia or on the level of peak parasitemia. However, mice depleted of CD8+ T cells experienced two recurrent bouts of parasitemia during the later stage of the infection and required more than 5 weeks to eliminate the parasites. After the peak parasitemia, which occurred in control and experimental animals on day 9, there was a sharp drop in parasitemia coinciding with a wave of reticulocytosis. Therefore, the contribution of the influx of reticulocytes, which are not the preferred host cell of this hemoprotozoan parasite, to limiting the parasitemia was also examined by determining the course of reticulocytosis during infection in control and T cell-depleted animals. Early in infection, there was a marked and comparable reticulocytosis in the peripheral blood of control and T cell-depleted mice; the reticulocytosis peaked on day 12 and coincided with the dramatic and sudden reduction in parasitemia occurring in all groups. In both control and CD8-depleted mice the percentage of reticulocytes decreased as the infection was resolved, whereas in CD4-depleted mice marked reticulocytosis correlated with high, persistent parasitemia. These results thus demonstrate that both CD4+ and CD8+ T cells are involved in acquired immunity to blood-stage P. chabaudi AS and that the influx of reticulocytes into the blood that occurs just after the peak parasitemia may contribute temporarily to limiting the parasitemia.


Nongynecologic applications of transvaginal sonography.
Transvaginal sonography has become an invaluable technique for examining the uterus and adnexa, primarily because it provides better spatial resolution than transabdominal sonography does. This characteristic also makes it useful for evaluating the nongynecologic structures in the pelvis. As many of these structures are imaged incidentally during gynecologic transvaginal sonography, familiarity with their normal and abnormal appearances is important. With minor modifications in technique, targeted studies of these structures are easily performed. We illustrate the technique used, normal anatomy seen, and abnormalities commonly encountered in transvaginal sonography of nongynecologic pelvic structures.


[Eyelid surgery in children with Down's syndrome].
To establish the best method of surgical correction of epicanthus in children with Down's syndrome. 18 patients underwent eyelid surgery. In 2 cases Spaeth's technique was used, in 5 cases-Blair-Brown's technique, and in 11 cases-Mustarde's technique. In 10 patients the correction of oblique position of palpebral fissure was additionally carried out. Comparative analysis showed that postoperative effects were good or excellent, and that Mustarde's technique seemed the best method for correction of epicanthus. The optimal time for this procedure was also assigned (3-6 years of age). Eyelid surgery connected with other plastic operations performed in children with Down's syndrome ensures blurring of mongoloid features. It has an advantageous effect on child's acceptation by others and on the results of psychosomatic rehabilitation as well.


[New geolocation system in Navarre to reduce urgent response times in mountainous and dispersed areas].
Identification of all urgent home alerts in mountainous and dispersed areas through the 112 system is normally done using the name of the farmhouse or dwelling, which makes it impossible to localize them with normal GPS means. The aim of this article is to obtain a valid geolocation system in out-of-hospital emergencies that is adapted to the nomenclature and geography of the area, and that can be implanted in all mobile health devices. This will provide exact precision without any loss of time in journeys, so as to avoid an increase in morbidity and mortality due to delays in attention given by professionals, whether or not they know the area. It should be possible to extrapolate this system to other points in the geography of Navarre and Spain. A geolocation tool was created adapted to the orography and specific nomenclature of the chosen pilot area (the Baztan valley) and it was made compatible with the two possible modes of current navigational software, with and without mobile data coverage (on line and off line). This system was integrated into non-corporative health mobile phones using KML archives and applied to the 913 geolocated farmhouses, with its real utility verified in the urgent home alerts registered between the months of May and September 2012. It was possible to reach the farmhouse (routing) requiring urgent attention without getting lost on the road or forest route, irrespective of access characteristics, because the localization of the destination had been registered beforehand in these files (this is the great difference with current GPS systems).


Personalized Touch-Based Exergame System for Unilateral and Bilateral Rehabilitation Training.
Background: Natural and intuitive interfaces that monitor and promote upper limb task-specific training need to be developed. This article presents the development and testing of a touch-based game system for training and assessment of unilateral (ULR) and bilateral (BLR) reaching movements. Interaction becomes intuitive and simple by introducing in-game touch and pressure onto virtual targets projected on a custom-made large touch panel. Materials and Methods: A custom-made App integrates exergames and a biomechanical model with advanced algorithms for movement analysis. It processes and manages data from a motion-tracking sensor and a large touch panel equipped with 1222 (26 × 47) piezoresistive sensors, including high-speed readout electronics and algorithms to measure touch points and contact forces during fingertip interaction. An experiment was conducted to evaluate the experience, motivation, and movements of healthy and stroke subjects when interacting with the proposed system. The panel height, dispersion of virtual targets, and required contact force were customized based on motor skills of each group of subjects. Results: Both groups of subjects showed high level of motivation and user experience when interacting with the virtual environments. Stroke subjects performed the task slower and traveled a similar path length than healthy subjects, but with shorter range of motion. The mechanical work and potential energy profiles of both groups are consistent with those achieved when reaching real objects. Conclusions: The proposed contact-based exergames are a feasible solution for performing natural and intuitive therapeutic ULR and BLR exercises. They elicit appropriate reaching movements and contact forces in healthy and stroke subjects. The spatial and temporal attributes of the proposed solution can be customized to influence the movement and energy expenditure of specific joints.


Operation timing does not affect outcome after coronary artery bypass graft surgery.
Human factors such as fatigue, circadian rhythms, scheduling, and staffing may have an impact on patient care over the course of a day across all medical specialties. Research by the transportation industry concludes that human performance is degraded by shift work, circadian rhythm disturbances, and prolonged duty. This study investigated whether the timing of coronary artery bypass graft surgery affects outcomes. The outcomes of coronary artery bypass graft surgery patients were analyzed according to the hour of the day, day of the workweek, month, and moon phase in which the surgery started. All patients who underwent isolated coronary artery bypass graft surgery between January 1, 1993 and July 1, 2006 were considered for the study.The primary outcome measurement was a compound morbidity outcome of six variables defined by the Society of Thoracic Surgeons. These outcomes included (1) in-hospital death, (2) acute postoperative myocardial infarction, (3) neurologic morbidity, including focal or global neurologic deficits or death without awakening, (4) serious infection morbidity consisting of sepsis syndrome or septic shock, (5) new-onset renal failure requiring dialysis, and (6) postoperative ventilatory support exceeding 72 h. The composite morbidity and in-hospital mortality rates were 4.8% and 1.4%, respectively. The number of cases each weekday, each month of the year, and during each phase of the moon were consistent. None of the time factors significantly affected the composite morbidity outcome. Elective coronary artery bypass graft surgery can be scheduled throughout the workday, any day of the work week and in any month of the year without compromising outcome.


Metabolic Characterization of a Rare Genetic Variation Within APOC3 and Its Lipoprotein Lipase-Independent Effects.
Plasma triglyceride levels have been implicated in atherosclerosis and coronary heart disease. Apolipoprotein C-III (APOC3) plays a key role in the hydrolysis of triglyceride-rich lipoproteins to remnant particles by lipoprotein lipase (LPL) and their uptake by the liver. A rare variant in APOC3(rs138326449) has been associated with triglyceride, very low-density lipoprotein, and high-density lipoprotein levels, as well as risk of coronary heart disease. We aimed to characterize the impact of this locus across a broad set of mainly lipids-focused metabolic measures. A high-throughput serum nuclear magnetic resonance metabolomics platform was used to quantify 225 metabolic measures in 13 285 participants from 2 European population cohorts. We analyzed the effect of the APOC3 variant on the metabolic measures and used the common LPL(rs12678919) polymorphism to test for LPL-independent effects. Eighty-one metabolic measures showed evidence of association with APOC3(rs138326449). In addition to previously reported triglyceride and high-density lipoprotein associations, the variant was also associated with very low-density lipoprotein and high-density lipoprotein composition measures, other cholesterol measures, and fatty acids. Comparison of the APOC3 and LPL associations revealed that APOC3 association results for medium and very large very low-density lipoprotein composition are unlikely to be solely predictable by the action of APOC3 through LPL. We characterized the effects of the rare APOC3(rs138326449) loss of function mutation in lipoprotein metabolism, as well as the effects of LPL(rs12678919). Our results improve our understanding of the role of APOC3 in triglyceride metabolism, its LPL independent action, and the complex and correlated nature of human metabolites.


Defining and Managing the Preanalytical Phase With FMECA: Automation and/or "Human" Control.
Our scope is to provide methodological elements on how to manage effectively the preanalytical phase in the laboratory testing process, by objectively measuring the risk connected to the phases handled by man with respect to those managed by machines. Preanalytical errors account for most of the mistakes related to laboratory testing and can affect patient care. Hence, it is necessary to manage the risk connected to the preanalytical phase, as required by certification and accreditation bodies. The risk assessment discloses the steps at greater risk and gives indications to make decisions. We have reviewed the state of art in the automation of the preanalytical phase, addressing needs and problems. We have used the proactive risk assessment methodology FMECA (Failure Mode, Effects, and Criticality Analysis) to identify the most critical phases in our preanalytical process and have calculated the risk associated. The most critical phases were the human controlled ones. In particular, the highest risk indexes were associated to manual acceptance of test orders, identification of the patients, tube labeling, and sample collection. Automation in the preanalytical phase is fundamental to replace, support, or extend the human contribution. Nevertheless each organization is different about workloads and competencies, so the most suitable management must be tailor-made in each context. We present a method by which each organization is able to find its best balance between automation and human contribution in the control of the preanalytical phase.


The influence of photodynamic reaction on R2C cells.
Photodynamic therapy (PDT) represents a therapeutic approach in which photosensitised neoplastic cells undergo destruction under effect of light. In this study we have attempted to define effects of photochemotherapy on R2C cells, sensitised with protoporphyrin IX (PpIX) and to find out whether inhibition of gene expression by cycloheximide affects development of lesions in the cells. The photosensitised cells were exposed to visible light and development of apoptotic and necrotic lesions was followed in the cells, using the fluorescent staining with propidium iodide and Hoechst 33342. The experiments demonstrated that PpIX and light, acting in parallel, induce development of apoptotic and necrotic lesions in R2C cells. Intensity of the lesions correlated with concentration of the applied photosensitiser and with duration of light exposure. Using cycloheximide, we also inhibited protein expression in cells photosensitised with protoporphyrin before they were exposed to light. In the latter case, development of apoptosis was clearly intensified which might be explained by inhibition of anti-apoptotic protein synthesis in the cells.


Tick species identification and molecular detection of tick-borne pathogens in blood and ticks collected from cattle in Egypt.
To address the lack of information on ticks infesting cattle in Egypt and the pathogens that they transmit, the current study aimed to (i) provide insight into tick species found on cattle in Egypt, (ii) identify the pathogens in ticks and their cattle hosts and (iii) detect pathogen associations in ticks and cattle. Tick samples and blood from their bovine hosts were collected from three different areas in Egypt (EL-Faiyum Oasis, Assiut Governorate and EL-Kharga Oasis). Tick species were identified by morphology and by sequence analysis of the cytochrome C oxidase subunit 1 (cox1) gene. Tick pools and blood samples from cattle were screened by the Reverse Line Blot hybridization (RLB) assay for the simultaneous detection of tick-borne pathogens, including Babesia, Theileria, Anaplasma, Ehrlichia, and Rickettsia spp., as well as the tick endosymbiont Midichloria mitochondrii. The RLB results were confirmed with specific conventional and semi-nested PCRs followed by sequencing. In total, 570 ticks (males, females and nymphs) were collected from 41 heads of cattle. Altogether 398 ticks belonged to the genus Hyalomma (397 Hyalomma excavatum and one Hyalomma scupense) while 172 ticks were identified as Rhipicephalus annulatus. Pooled H. excavatum ticks tested positive for several protozoa and bacteria with different minimum infection rates (MIRs): Theileria annulata (18.1 %), Babesia occultans (1.8 %), Anaplasma marginale (28.5 %), Anaplasma platys (0.25 %), Midichloria mitochondrii (11.6 %), Ehrlichia chaffeensis-like (1.8 %) and Ehrlichia minasensis (1 %). In R. annulatus, several agents were identified at different MIRs: T. annulata (2.3 %), B. bovis (0.6 %), A. marginale (18.0 %), A. platys (1.2 %), M. mitochondrii (2.9 %), E. minasensis (0.6 %). Pathogens co-detection in tick pools revealed A. marginale and T. annulata in 13.3 % samples followed by the co-detection of A. marginale and M. mitochondrii (8.4 %). In addition, triple co-detection with A. marginale, T. annulata and M. mitochondrii were found in 5.3 % of the tick pools. In cattle, the most common coinfection was with A. marginale and T. annulata (82.9 %) followed by the coinfection between A. marginale, T. annulata and B. bovis (4.9 %), A. marginale and B. bigemina (2.4 %) and finally the coinfection between T. annulata and B. occultans (2.4 %). Anaplasma platys, Babesia occultans, and E. minasensis were detected for the first time in Egypt in both cattle and ticks. These findings should be taken in consideration regarding human and animal wellbeing by the public health and veterinary authorities in Egypt.


"Failure to thrive" in elderly depressed patients: a new concept or a different name for an old problem?
With increasing frequency one may encounter the term "failure to thrive (FTT)" as applied to elderly patients. FTT in elderly patients is characterized by an insidious deterioration in their self-care abilities, loss of weight, loss of interest in social activities, a gradual decline in physical and/or cognitive function, and increased dependency on family members. The deterioration is beyond the expected, age-associated, "normal" decline. Depression is considered to be only one of the possible causes of FTT in the elderly. However, we suggest that the term, "FTT," as applied to elderly, depressed patients, does not appear to have intrinsic clinical value in that it describes a situation which represents an extreme form of the depressed syndrome rather than a separate clinical entity. It seems that early recognition of FTT would lead to appropriate supportive treatment being instituted before an advanced level of deterioration is reached. However, early diagnosis of the depression should have the same result and should lead to appropriate antidepressant treatment combined with vigorous nutritional intervention as well. The clinical problem which may lead to a delay in treatment of "FTT" affected elderly depressed patients is not a failure to diagnose "FTT" but a failure to diagnose depression.


Fluorescence and chemiluminescence enzyme immunoassays of 17 alpha-hydroxyprogesterone in dried blood spotted on filter paper.
Enzyme immunoassays for 17 alpha-hydroxyprogesterone (17-OHP) were developed. Horseradish peroxidase (HRP), glucose oxidase (GOD), invertase (INV) and glucose-6-phosphate dehydrogenase (G6PDH) were used as label enzymes. Double antibody coated beads or tubes were used for separating the bound and free fractions. Antisera used were prepared by using 4-carboxyethylthio-17-OHP and 3-carboxymethyl oxime-17-OHP-bovine serum albumin as immunogens. The bridge heterologous system was more sensitive than other site heterologous and homologous systems. The minimum amounts of 17-OHP detected were 0.25 and 1.0 pg/tube for fluorescence EIAs using HRP and GOD, and 0.1, 10 and 0.1 pg/tube for chemiluminescence EIAs using GOD, INV and G6PDH, respectively. The reproducibility and correlation with RIA were also studied. The present study demonstrates the feasibility of a neonatal screening for congenital adrenal hyperplasia.


Home care expenses for the disabled elderly.
This article presents descriptive statistics from the 1982 Long-Term Care Survey on noninstitutionalized elderly Americans with limitations in activities of daily living (ADL) and instrumental activities of daily living (IADL). The focus of this article is on private expenses for home-based care related to ADL and IADL limitations. We describe the amounts of out-of-pocket payments expended relative to the characteristics of the home-based, disabled elderly population. We also discuss several possible implications of the findings for policymakers and further research.


Effects of caloric restriction and aerobic exercise on circulating cell-free mitochondrial DNA in patients with moderate to severe chronic kidney disease.
Circulating cell-free mitochondrial DNA (ccf-mtDNA) may induce systemic inflammation, a common condition in chronic kidney disease (CKD), by acting as a damage-associated molecular pattern. We hypothesized that in patients with moderate to severe CKD, aerobic exercise would reduce ccf-mtDNA levels. We performed a post hoc analysis of a multicenter randomized trial (NCT01150851) measuring plasma concentrations of ccf-mtDNA at baseline and 2 and 4 mo after aerobic exercise and caloric restriction. A total of 99 participants had baseline ccf-mtDNA, and 92 participants completed the study. The median age of the participants was 57 yr, 44% were female and 55% were male, 23% had diabetes, and 92% had hypertension. After adjusting for demographics, blood pressure, body mass index, diabetes, and estimated glomerular filtration rate, median ccf-mtDNA concentrations at baseline, 2 mo, and 4 mo were 3.62, 3.08, and 2.78 pM for the usual activity group and 2.01, 2.20, and 2.67 pM for the aerobic exercise group, respectively. A 16.1% greater increase per month in ccf-mtDNA was seen in aerobic exercise versus usual activity (P = 0.024), which was more pronounced with the combination of aerobic exercise and caloric restriction (29.5% greater increase per month). After 4 mo of intervention, ccf-mtDNA increased in the aerobic exercise group by 81.6% (95% confidence interval: 8.2-204.8, P = 0.024) compared with the usual activity group and was more marked in the aerobic exercise and caloric restriction group (181.7% increase, 95% confidence interval: 41.1-462.2, P = 0.003). There was no statistically significant correlation between markers of oxidative stress and inflammation with ccf-mtDNA. Our data indicate that aerobic exercise increased ccf-mtDNA levels in patients with moderate to severe CKD.NEW & NOTEWORTHY The effects of prolonged exercise on circulating cell-free mitochondrial DNA (ccf-mtDNA) have not been explored in patients with chronic kidney disease (CKD). We showed that 4-mo aerobic exercise is associated with an increase in plasma ccf-mtDNA levels in patients with stages 3 or 4 CKD. These changes were not associated with markers of systemic inflammation. Future studies should determine the mechanisms by which healthy lifestyle interventions influence biomarkers of inflammation and oxidative stress in patients with CKD.


Differential effects of sarcolemmal and mitochondrial K(ATP) channels activated by 17 beta-estradiol on reperfusion arrhythmias and infarct sizes in canine hearts.
We have demonstrated the effects of estrogen on modulation of ATP-sensitive K(+) channels; however, the subcellular location of these channels is unknown. The purpose of the present study was to investigate the role of the sarcolemmal and mitochondrial ATP-sensitive K(+) channels in a canine model of myocardial infarction after stimulation with 17 beta-estradiol. Anesthetized dogs were subjected to 60 min of the left anterior descending coronary artery occlusion followed by 3 h of reperfusion. Infarct size was markedly reduced in estradiol-treated dogs compared with controls (14 +/- 6 versus 42 +/- 6%, P < 0.0001), indicating the effective dose of estradiol administrated. Pretreatment with the mitochondrial ATP-sensitive K(+) channel antagonist 5-hydroxydecanoate completely abolished estradiol-induced cardioprotection. The sarcolemmal ATP-sensitive K(+) channel antagonist 1-15-12-(5-chloro-o-anisamido)ethyl-methoxyphenyl)sulfonyl-3-methylthiourea (HMR 1098) did not significantly attenuate estradiol-induced infarct size limitation. In addition, estradiol administration significantly reduced the incidence and duration of reperfusion-induced ventricular tachycardia and ventricular fibrillation. Although 5-hydroxydecanoate alone caused no significant effect on the incidence of reperfusion arrhythmias in the presence or absence of estradiol, the administration of HMR 1098 abolished estrogen-induced improvement of reperfusion arrhythmias. Pretreatment with the estrogen-receptor antagonist faslodex (ICI 182,780) did not alter estrogen-induced infarct-limiting and antiarrhythmic effects. These results demonstrate that estrogen is cardioprotective against infarct sizes and fatal reperfusion arrhythmias by different ATP-sensitive K(+) channels for an estrogen receptor-independent mechanism. The infarct size-limiting and antiarrhythmic effects of estrogen were abolished by 5-hydroxydecanoate and HMR 1098, suggesting that the effects may result from activation of the mitochondrial and sarcolemmal ATP-sensitive K(+) channels, respectively.


Myological reconstruction of the pelvic girdle and hind limb of the giant titanosaurian sauropod dinosaur Dreadnoughtus schrani.
Osteological correlates preserve more readily than their soft tissue counterparts in the fossil record; therefore, they can more often provide insight into the soft tissue anatomy of the organism. These insights can in turn elucidate the biology of these extinct organisms. In this study, we reconstruct the pelvic girdle and hind limb musculature of the giant titanosaurian sauropod Dreadnoughtus schrani based on observations of osteological correlates and Extant Phylogenetic Bracket comparisons. Recovered fossils of Dreadnoughtus exhibit remarkably well-preserved, well-developed, and extensive muscle scars. Furthermore, this taxon is significantly larger bodied than any titanosaurian for which a myological reconstruction has previously been performed, rendering this contribution highly informative for the group. All 20 of the muscles investigated in this study are sufficiently well supported to enable reconstruction of at least one division, including reconstruction of the M. ischiocaudalis for the first time in a sauropod dinosaur. In total, 34 osteological correlates were identified on the pelvic girdle and hind limb remains of Dreadnoughtus, allowing the reconstruction of 14 muscles on the basis of Level I or Level II inferences (i.e., not Level I' or Level II' inferences). Comparisons among titanosaurians suggest widespread myological variation, yet potential phylogenetic and other paleobiologic patterns are often obscured by fragmentary preservation, infrequent myological studies, and lack of consensus on the phylogenetic placement of many taxa. However, a ventrolateral accessory process is present on the preacetabular lobe of the ilium in all of the largest titanosauriforms that preserve this skeletal element, suggesting that the presence of this process (representing the origin of the M. puboischiofemoralis internus part II) may be associated with extreme body size. By identifying such myological patterns among titanosauriforms, we can begin to address specific evolutionary and biomechanical questions related to their skeletal anatomy, how they were capable of leaving wide-gauge trackways, and resulting locomotor attributes unique to this clade.


Progressive multifocal leucoencephalopathy in AIDS camouflaged with catatonia: A wolf in sheep's clothing.
Progressive multifocal leucoencephalopathy (PML) may pose a clinical and diagnostic dilemma. The patient may remain in a protracted psychotic state with negative symptoms, without overt features of dementia. The condition blends with catatonia, and eventually with akinetic mutism in a patient of AIDS in the absence of clinical evidence of an immunocompromised state. The present case report highlights the need for an in-depth clinical, biochemical and MRI assessment of patients with catatonia and akinetic mutism. Stupor of an 'akinetic mutism' pattern seems an important indication for HIV screening, particularly in high-risk patients.


[Occurrence and nature of hyperamylasemia in chronic alcoholics].
The purpose of this work was: a) the prospective study of the prevalence of hyperamylasemia in 100 patients with chronic alcoholism; b) the determination of the serum isoamylase distribution in patients with hyperamylasemia by an inhibitor assay; c) the search of the origin of elevated serum isoamylase S. Moderate hyperamylasemia was found in 15 patients. The importance of alcohol abuse, the prevalences of cirrhosis and smokers were not statistically different from those observed in normoamylasemic patients. After one week of hospitalization, serum amylase was still elevated in 11 of 14 alcoholic patients. Hyperamylasemia was due to an increase in the isoamylase P in 5 cases, in the isoamylase S in 7 cases, and in both forms in 3 cases. Activities of serum lipase and isoamylase P were roughly parallel. Only two out of 8 patients with elevated isoamylase P had chronic pancreatitis. The salivary origin of elevated isoamylase S was suspected in only one out of 10 patients. This work shows that the origin of moderate hyperamylasemia, observed in alcoholic patients, is often extrapancreatic. It is suggested that the dosage of serum lipase simpler than that of isoamylases, may be routinely used in chronic alcoholic patients for diagnostic purposes.


The plasma homocysteine levels are increased in polycystic ovary syndrome.
Women with polycystic ovary syndrome (PCOS) have several cardiovascular disease risk factors. Since hyperhomocysteinemia is associated with early atherosclerosis, it was postulated that the homocysteine levels are higher in PCOS patients than in control subjects which, therefore, may explain the cardiovascular disease risk. Thirty-five women with PCOS and 20 healthy subjects were studied. Endocrine assays, lipid profile, homocysteine and insulin level determinations, and ultrasound evaluation were performed in all subjects. We found significantly higher mean plasma homocysteine concentrations in patients with PCOS as compared with controls (10.4 +/- 4.4 vs. 7.2 +/- 1.5 ng/dl; p < 0.003). These data show that in PCOS early atherosclerosis is not exclusively dependent on hyperinsulinemia and elevated lipid profile - PCOS patients are exposed to significantly higher homocysteine levels which might increase the cardiovascular disease risk.


Fracture of the femoral component in cementless total knee arthroplasty.
Records of sales revealed that 6172 Ortholoc II cementless total knee femoral components with double bead layers were sold between January 1986 and December 1987. Sixteen thousand two hundred thirty Ortholoc II femoral implants with single bead layers were sold between December 1986 and January 1990. Fractures of the femoral components were reported in 32 knees; all but one occurred in femoral components with porous surfaces consisting of two layers of sintered beads. The overall minimum rate of failure for all sizes with double bead layers was 0.42%. The rate varied with the size of the implant and was much greater in smaller implants. The rate of failure was 0.82% in 852 small components, 0.37% in 2416 medium components, 0.29% in 1729 large components, and 0.09% in 1175 extra-large components. The differences in failure rates were statistically significant for all sizes of implants when compared with other sizes. Sixteen thousand two hundred thirty Ortholoc II components with a single layer of beads were sold worldwide between December 1986 and January 1989. One implant (medium size) failed 18 months after surgery. The minimum rate of failure in the single bead layer implants is 0.006%. This failure rate is statistically significantly less than that of the double bead layer implants. All failures occurred at the junction between one of the bevel surfaces and the distal surface of the implant. In all cases, crack propagation was initiated at the inner surface. This suggests that bending stresses had developed and had opened (straightened) the femoral component.(ABSTRACT TRUNCATED AT 250 WORDS)


Serum Vitamin D Status and Outcome among Critically Ill Children Admitted to the Pediatric Intensive Care Unit in South India.
To determine the vitamin D status and the association between vitamin D status and the clinical outcome of critically ill children admitted to pediatric intensive care unit (PICU) in South India. Fifty-four consecutive children with medical and surgical diagnoses were included with parental consent. Severity of illness was assessed using PIM-2 score; Sequential Organ Failure Assessment Cardiovascular Score (CV-SOFA) was used to describe vasopressor use. Serum for 25(OH) D levels was obtained as close as possible to the ICU admission. Vitamin D deficiency was defined as serum 25(OH) D level < 20 ng/ml (50 nmol/L). Primary outcome measures were serum 25(OH) D level and in-hospital all cause mortality. Secondary outcomes were illness severity, vasopressor requirement, use of mechanical ventilation and duration of ICU stay. Of the 54 children, two were excluded due to insufficient serum for vitamin D analysis. Median age was 17.5 mo (IQR = 4.5-78); 38.5 % were infants. Higher age was associated with low vitamin D levels (r s = -0.34; p 0.01). Median serum 25(OH) D level was 25.1 ng/ml (IQR = 16.2-34.2). Shock (30.8 %), CNS conditions (23.1 %) and respiratory illnesses (21.2 %) were the three most common reasons for admission to the PICU. Vitamin D deficiency was seen in 40.3 % of the critically ill children. Higher PIM score or SOFA score were associated with low vitamin levels (r s = -0.29, p 0.04 and r s = -0.29, p 0.05 respectively). Children who were mechanically ventilated had a significantly lower median serum 25(OH) D level than those who were not on ventilation [19.5 ng/ml (IQR = 14.6-27.7)] vs. 32.1 ng/ml[(IQR = 16.5-50.9), p 0.01]. Serum 25(OH) D level was also positively associated with serum calcium levels (r s = 0.32, p 0.03). The proportion of children who died or were discharged terminally at parental request was 23.8 % among those with serum 25(OH) D level < 20 ng/ml as compared to 16.1 % among those with serum 25(OH) D level > 20 ng/ml (p 0.49). Vitamin D deficiency is common among pediatric patients admitted to PICU in South India. Low serum 25(OH) D level was associated with higher severity of illness, need for mechanical ventilation, more vasopressor use and lower serum calcium levels. No association between vitamin D status and mortality was demonstrated.


Gene therapy based in antimicrobial peptides and proinflammatory cytokine prevents reactivation of experimental latent tuberculosis.
Mycobacterium tuberculosis (Mtb) latent infection can lead to reactivation. The design of new strategies to prevent it is an important subject. B6D2F1 mice were infected intratracheally with a low dose of Mtb H37Rv to induce chronic infection. After 7 months, mice were treated with one dose of recombinant adenoviruses encoding TNFα, β defensin-3 and LL37. Immunosupression was induced 1 month later with corticosterone. In comparison with the control group, mice treated with adenoviruses showed significantly less bacterial load and pneumonia, the adenoviruses encoding TNFα and LL37 being the most efficient. Gene therapy based in a proinflammatory cytokine or antimicrobial peptides is a potentially useful system to prevent reactivation of latent tuberculosis.


Effects of single-session dietary counseling by dieticians on salt reduction in cardiology outpatients who consumed large amounts of salt.
The purpose of the present study was to assess the effects of single-session dietary counseling on salt restriction in Japanese cardiology outpatients as assessed using spot urine measurements. A total of 72 patients (73±11 years old, including 30 females) who visited a cardiology outpatient clinic and had a salt intake of >8 g/day were included in this study. The patients received dietary counseling for salt restriction by expert dieticians at the time of enrollment. The daily dietary salt intake was estimated using the spot urine test at baseline prior to dietary counseling, at 3-9 weeks (next office visit), and at 24-52 weeks during follow-up evaluations. The baseline level of estimated salt excretion was 11.3±1.5 g/day, which was reduced to 9.6±2.3 g/day (P<0.01) at 3-9 weeks, but increased again at 24-52 weeks to 10.4±2.1 g/day, which was less than the baseline value (P=0.034 vs. 3-9 weeks; P=0.025 vs. baseline). The numbers of patients who achieved salt excretion levels of <6.0 and <8.0 g/day at 3-9 weeks were 4 (5.6%) and 19 (26%) patients, respectively, and were further reduced to no patients (0%; P=0.043 vs. 3-9 weeks) and 9 (13%; P=0.035 vs. 3-9 weeks) patients at 24-52 weeks of follow-up evaluation, respectively. In conclusion, the efficacy of dietary counseling by expert dieticians in restricting the salt intake of patients who consumed large amounts of salt was modest and temporary. Multiple nutritional- and behavioral-oriented approaches should be considered to achieve further reductions in salt intake.


Nucleotide Metabolism in Salt-Stressed Zea mays L. Root Tips: I. Adenine and Uridine Nucleotides.
Corn plants (Zea mays L. cv Pioneer 3906) were grown in a glass house on control and saline nutrient solutions, in winter and summer. There were two saline treatments, both with osmotic potential = -0.4 megapascal but with different Ca(2+)/Na(+) ratios: 0.03 and 0.73. Root tips and shoot meristems (culm tissue) of 26 day-old plants were analyzed for nucleotides to ascertain if there were correlations between nucleotide pool size and the reduced growth on saline cultures. Several other cell components also were determined. Plants grown in winter were only half as large as those grown in summer mainly because of the lower light intensity and lower temperature. But the relative yield reduction on salt treatment compared to the control was similar in winter and summer. The two different salt treatments caused similar yield reductions. Neither salt treatment affected nucleotide pools in culm tissue, with the possible exception of UDPG in winter. In the case of root tips, salt treatment had little or no effect on nucleotide pool sizes in winter when many already seemed near a critical minimum, but in summer it reduced several pools including ATP, total adenine nucleotide, UTP, total uridine nucleotide, and UDP-glucose. The reductions were greatest on the salt treatment with low Ca(2+)/Na(+). There was no simple correlation between the effects of salt stress on growth and on nucleotide pool size. The nucleotide pools of culm tissue indicated that in some respects this tissue was effectively insulated from the salt stress. Roots that were in direct contact with the saline solution indicated significant reductions in nucleotide pools only in the summer whereas growth was reduced both summer and winter. It is possible that the nucleotide concentrations of root cells in winter were already near a critical minimum so that nucleotide synthesis and growth were tightly linked. Significant reductions in nucleotide pools that would be expected to affect growth were more evident in summer when pools were larger and growth was more rapid. But even where ATP and total adenine nucleotides were reduced, the ratio of ATP:ADP and the adenylate energy charge remained unchanged indicating an active adenylate kinase that had access to most of the adenine nucleotide pools, and possible catabolism of excess AMP.


A new approach to the prevention of endless loop tachycardia in DDD and VVD pacing.
Endless loop tachycardia (ELT) is a possible complication in dual chamber pacing; it is usually prevented by programming the atrial refractory period (PVARP) longer than the retrograde ventriculoatrial (VA) conduction interval; this in some patients limits the upper rate. In 15 patients with a DDD (nine patients) or a single-pass lead VDD pacemaker (six patients) and retrograde atrial activation, telemetric recording documented a significant difference in amplitude of antegrade, and retrograde atrial potentials (VDD 1.21 +/- 0.32 mV vs 0.56 +/- 0.23 mV, P = 0.008; DDD 2.7 +/- 1 vs 1.8 +/- 1 mV, P = 0.038; Student's t-test for paired data). In 3/15 patients ELT stopped after programming of atrial sensitivity to a value greater than the retrograde P wave amplitude; in 11/15 patients this occurred at a sensing value lower than or equal to retrograde P wave amplitude with a high pass band filter operating. One patient required PVARP lengthening. Holter monitoring showed no more ELTs. In most patients with a DDD or single-pass lead VDD pacemaker with widely programmable sensing amplitude and Hi/Low bandpass filters, individual programming of atrial channel sensitivity prevents ELT without affecting the PVARP and, consequently, upper rate limit.


Accuracy and reliability of feature selection by Chinese fingerprint examiners.
The selection of minutiae is a critical part of the analysis phase within the fingerprint identification methodology, known as analysis-comparison-evaluation-verification. This study assessed the accuracy and reliability of the minutiae selections of 92 Chinese fingerprint examiners during the analysis phase, absent an exemplar print, of the fingerprint identification process. Specifically, we measured the accuracy (trueness) of their annotation of minutiae, and we measured their reliability which is the reproducibility and repeatability in their annotations in one complex mark by using R software. We observed significant variation within inter- and intra-examiner annotations of the minutiae. We saw no statistically significant differences for the variability of minutiae annotations based on the participant's sex or years of experience.


Functional cross-talk between angiotensin II and epidermal growth factor receptors in NIH3T3 fibroblasts.
The main angiotensin (Ang) II subtype receptors (AT1R and AT2R) are involved in cellular growth processes and exert functionally antagonistic effects. To characterize the mechanisms by which Ang II receptors influence growth, by investigating the interactions between Ang II subtype receptors and epidermal growth factor (EGF) receptors on mitogen-activated protein kinase (MAPK) pathway activation. The experiments were performed using a mouse fibroblast cell line, NIH3T3, by transient co-transfection with rat AT1R or AT2R expression vectors, or both. Extracellular-signal-regulated kinase (ERK)1/2 phosphorylation was analysed by western blot and the ERK activity was evaluated using PathDetect, an in-vivo signal transduction pathway trans-reporting system. Selective Ang II receptor antagonists (losartan for AT1R and PD123319 for AT2R) were used to investigate the contributions of each receptor to the response observed. Our data show that, in this cellular model, both Ang II receptors phosphorylate ERK1/2. However, in the cells expressing AT1R, the EGF-induced MAPK pathway was enhanced in the presence of Ang II in a synergistic fashion. In contrast, a reduction of EGF-induced MAPK activation was observed in the cells expressing AT2R. In cells expressing both Ang II subtype receptors, Ang II promoted an enhancement of EGF-induced MAPK activation. However, in the presence of the AT1R antagonist, losartan, the effect of EGF was reduced. These data indicate the existence of an opposite cross-talk of AT1R and AT2R with EGF receptors, and suggest a complex functional interaction between these pathways in the regulation of cellular growth processes.


Risk of QTc prolongation in a cohort of opioid-dependent HIV-infected patients on methadone maintenance therapy.
Concern regarding the QTc interval in human immunodeficiency virus (HIV)-infected patients has been growing in recent years, and cases of prolonged QTc interval and torsades de pointes have been described in HIV-infected patients on methadone therapy. This study aimed to determine the prevalence and factors associated with long QTc interval in a cohort of opioid-dependent HIV-infected patients on methadone maintenance therapy. A cross-sectional study was conducted in opioid-dependent HIV-infected patients on methadone maintenance therapy at a drug abuse outpatient center. Patients with any cardiac disease, drug-positive urine test, electrolyte abnormalities, and changes in their antiretroviral therapy (ART) or methadone doses in the last 2 months were excluded. Heart rate and QT interval in lead II were measured using the Bazett formula. Ninety-one patients were included: 58 (63.7%) were men with a median age of 44.5 years and 68 of 91 (74.7%) were on ART. Median methadone dose was 70 mg/day (range 15-250 mg/day) and mean QTc interval was 438 ± 34 ms. Prolonged QTc interval (>450 ms) was documented in 33 of 91(36.3%) patients, and 3 of 91 (3.2%) had QTc >500 ms. On multiple linear regression analysis, methadone doses (P = .005), chronic hepatitis C-induced cirrhosis (P = .008), and being ART-naive (P = .036) were predictive of prolonged QTc. The prevalence of prolonged QTc interval in opioid-dependent HIV-infected patients on methadone maintenance therapy is high. Risk factors for prolongation of the QTc interval are chronic hepatitis C-induced cirrhosis, higher methadone doses, and being ART-naive. Thus, electrocardiographic monitoring is required to minimize cardiovascular morbidity and mortality in this specific HIV group.


Dental age estimation and third molars: a preliminary study.
The aim of the present investigation was to reconstruct the chronological age based on the dental developmental stages of third molars evaluated on orthopantomograms. A total of 1175 orthopantomograms were assembled from patients of Caucasian origin between 16 and 22 years of age. Each third molar present was scored by two observers according to a 10-stage developmental scale. The kappa statistics measured the intra- and inter-observer reliability. The general statistical analysis was based on multiple regression analysis in order to obtain multiple regression formulas for dental age estimation based on the number of third molars present on the evaluated orthopantomogram. No regression models were statistically significant when there was only one-third molar present because of the relatively small number of orthopantomograms that fitted this criterion. A strong agreement was found between the intra- and inter-observer measurements. The statistical analysis revealed both for males and females high Pearson correlation coefficients between contralateral third molars and smaller coefficients between antimeres. The obtained multiple regression formulas are only applicable in certain specified conditions, for instance when four third molars are present the following formulas should be used in a Caucasian male "age=10.2000+0.5122UL+0.5273LL" (developmental stage of upper and lower left third molars) or in case of a female "age=13.6206+0.1933UR+0.5080LR" (developmental stage of upper and lower right third molars). This investigation revealed that the chronological age of a Caucasian individual may be estimated based on regression formulas with a S.D. of 1.52 or 1.56 years for males and females, respectively, when all four third molars are present.


Establishment of Four Induced Pluripotent Stem Cell Lines from CD34+ Hematopoietic Stem and Progenitor Cells from a Patient Diagnosed with an Invasive Lobular Mammary Carcinoma.
CD34+ cells were isolated from peripheral blood of a breast cancer patient. By the introduction of five integration-free episomal vectors, the CD34+ cells were successfully reprogrammed and resulted in four iPSC clones. Flow Cytometry, reverse transcriptase PCR and immunocytochemistry confirm a robust expression of pluripotency factors and the concomitant loss of exogenous reprogramming plasmids. The maintenance of genomic integrity was confirmed by array-based comparative genomic hybridization and iPSCs harbored the capacity to differentiate into all three germ layers. Here, we present the generation and characterization of four iPSC lines that will find application in the field of breast cancer research.


Resonance Raman evidence for protein-induced out-of-plane distortion of the heme prosthetic group of mammalian lactoperoxidase.
Resonance Raman spectra have been acquired for resting state mammalian lactoperoxidase, LPO(N), and its six-coordinate, low-spin (6CLS) cyanide complex, LPO(CN), as well as for various heme l containing fragments resulting from partial or complete proteolytic digestion. These proteolytic fragments provide a useful set of reference compounds for analysis of the LPO(N) and LPO(CN) enzymes, using various ligands to generate well-defined five-coordinate and six-coordinate high-spin (5CHS and 6CHS) species. In addition, these model compounds, which contain zero, one, or two covalently attached ester linkages to polypeptide chains, are quite useful for determining the extent to which the presence of the ester linkages at the heme periphery affects the characteristic heme resonance Raman marker bands. The spectral results not only provide strong evidence for the formulation of the resting state enzyme as a 6CHS species, but also confirm the previously documented anomalous intensities of several low-frequency resonance Raman bands, which are most reasonably interpreted to arise from a protein-induced out-of-plane distortion of the heme l macrocycle mediated by the covalent ester linkages to the associated polypeptide residues of the intact protein.