Implementation of a pilot accountable care organization payment model and the use of discretionary and nondiscretionary cardiovascular care.
Accountable care organizations (ACOs) seek to reduce growth in healthcare spending while ensuring high-quality care. We hypothesized that accountable care organization implementation would selectively limit the use of discretionary cardiovascular care (defined as care occurring in the absence of indications such as myocardial infarction or stroke), while maintaining high-quality care, such as nondiscretionary cardiovascular imaging and procedures. The intervention group was composed of fee-for-service Medicare patients (n=819 779) from 10 groups participating in a Medicare pilot accountable care organization, the Physician Group Practice Demonstration (PGPD). Matched controls were patients (n=934 621) from nonparticipating groups in the same regions. We compared use of cardiovascular care before (2002-2004) and after (2005-2009) PGPD implementation, studying both discretionary and nondiscretionary carotid and coronary imaging and procedures. Our main outcome measure was the difference in the proportion of patients treated with imaging and procedures among patients of PGPD practices compared with patients in control practices, before and after PGPD implementation (difference-in-difference). For discretionary imaging, the difference-in-difference between PGPD practices and controls was not statistically significant for discretionary carotid imaging (0.17%; 95% confidence interval, -0.51% to 0.85%; P=0.595) or discretionary coronary imaging (-0.19%; 95% confidence interval, -0.73% to 0.35%; P=0.468). Similarly, the difference-in-difference was also minimal for discretionary carotid revascularization (0.003%; 95% confidence interval, -0.008% to 0.002%; P=0.705) and coronary revascularization (-0.02%; 95% confidence interval, -0.11% to 0.07%; P=0.06). The difference-in-difference associated with PGPD implementation was also essentially 0 for nondiscretionary cardiovascular imaging or procedures. Implementation of a pilot accountable care organization did not limit the use of discretionary or nondiscretionary cardiovascular care in 10 large health systems.


A systematic review and meta-analysis of treatments for acrophobia.
To review the literature on the comparative efficacy of psychological, behavioural and medical therapies for acrophobia (fear of heights). Multiple databases were searched through the Cochrane Common Mental Disorders review group on 1 December 2015. The data were extracted independently and were pooled using RevMan version 5.3.5. The main outcome measures were changes from baseline on questionnaires for measurement of fear of heights, such as the Acrophobia Questionnaire (AQ), Attitude Towards Height Questionnaire (ATHQ), and behavioural avoidance tests. Individual and pooled analyses were conducted. Sixteen studies were included. Analysis of pooled outcomes showed that desensitisation (DS) measured by the post-test AQ anxiety score (standardised mean difference [SMD], -1.24; 95% CI, -1.88 to -0.60) and in vivo exposure (IVE) were effective in the short term compared with control (SMD, -0.74; 95% CI, -1.22 to -0.25). IVE was not effective in the long term (SMD, -0.34; 95%CI -0.76 to 0.08) and there were no follow-up data for DS. Virtual reality exposure (VRE) therapy was effective when assessed with the ATHQ but not the AQ. Augmentation of VRE with medication was promising. The number needed to treat (NNT) ranged from 1.4 (95% CI, 1.0 to 2.2) for IVE therapy with oppositional actions (a psychological process) versus waitlist control to an NNT of 6.0 (95% CI, 2.8 to 35.5) for the rapid phobia cure (a neurolinguistic programming technique) versus a mindfulness exercise as the control activity. It was often unclear if there were biases in the included studies. A range of therapies are effective for acrophobia in the short term but not in the long term. Many of the comparative studies showed equivalence between therapies, but this finding may be due to a type II statistical error. The quality of reporting was poor in most studies.


Successful cadaveric transplantation of a splitted crossed fused disc type ectopic kidney to two patients with end-stage renal disease.
Cadaveric donors with congenital renal anomalies are often refused because of technical difficulties. As the waiting periods for kidney transplants continue to increase, transplant centers need to consider them also as potential donors. This paper describes transplantation of a crossed fused disc type ectopic kidney to two patients with end-stage renal disease, after parenchymal transection. The transplants were successful with minimal complications, and the recipients had immediate graft function. It is now one year from transplantation, with excellent renal functions.


Use of rapid-scan EPR to improve detection sensitivity for spin-trapped radicals.
The short lifetime of superoxide and the low rates of formation expected in vivo make detection by standard continuous wave (CW) electron paramagnetic resonance (EPR) challenging. The new rapid-scan EPR method offers improved sensitivity for these types of samples. In rapid-scan EPR, the magnetic field is scanned through resonance in a time that is short relative to electron spin relaxation times, and data are processed to obtain the absorption spectrum. To validate the application of rapid-scan EPR to spin trapping, superoxide was generated by the reaction of xanthine oxidase and hypoxanthine with rates of 0.1-6.0 μM/min and trapped with 5-tert-butoxycarbonyl-5-methyl-1-pyrroline-N-oxide (BMPO). Spin trapping with BMPO to form the BMPO-OOH adduct converts the very short-lived superoxide radical into a more stable spin adduct. There is good agreement between the hyperfine splitting parameters obtained for BMPO-OOH by CW and rapid-scan EPR. For the same signal acquisition time, the signal/noise ratio is >40 times higher for rapid-scan than for CW EPR. Rapid-scan EPR can detect superoxide produced by Enterococcus faecalis at rates that are too low for detection by CW EPR.


Electrically switchable emission in terahertz quantum cascade lasers.
Electrically switchable emission in a terahertz quantum cascade laser is demonstrated. Two active region designs are incorporated into the same waveguide, forming a heterogeneous cascade that lases at frequencies around 2.6 THz and 3.0 THz. We find that the position of the active regions within the waveguide does not effect the sequence in which the two colours reach laser threshold. The devices show good performance, with 2.6 THz and 3.0 THz modes operating up to 60K and 91K respectively and displaying thresholds as low as 79 Acm(-2) for the 2.6 THz mode.


Rasch analysis of the Dutch Health Assessment Questionnaire disability index and the Health Assessment Questionnaire II in patients with rheumatoid arthritis.
The Health Assessment Questionnaire (HAQ) disability index (DI) is the most common self-reported measure of physical disability in rheumatoid arthritis (RA). Recently, the HAQ-II was developed in the US as a short, valid, and reliable alternative using Rasch analysis. Our objective was to compare the scaling properties of the HAQ DI and HAQ-II in Dutch patients with RA. We used data from 472 patients with confirmed RA. Internal construct validity of the HAQ versions was assessed using Rasch analysis. Additionally, external construct validity was assessed by examining correlates with other outcome measures. The HAQ DI had a large floor effect, with 9.5% of the patients indicating no disability compared with 4.3% for the HAQ-II. Both versions were unidimensional and adequately fit the Rasch model, containing only 1 nonfitting item. Additionally, 2 HAQ-II items demonstrated overfit and a high residual correlation, suggesting overlap or redundancy in item content. The HAQ-II demonstrated better item separation, indicating that it covered a wider range of physical function. Item difficulty estimates were reasonably well spread for the HAQ-II, whereas the HAQ DI items tended to cluster around similar difficulty levels. Both scales contained several items with differential item functioning by sex, age, or disease duration. Both scales demonstrated the expected pattern of correlations with other outcome measures. The results indicate that both the HAQ DI and HAQ-II are psychometrically robust measures of physical function. The Rasch-developed HAQ-II, however, has several favorable scaling properties, including a better scale length and a reduced floor effect.


Deceived versus nondeceived participants' perceptions of scientific and applied psychology.
Research examining the possible effects of deceptive research participation on participants' perceptions of psychology has yielded equivocal results. The present study's goal was to clarify the possible effects of participation in mildly deceptive research on participants' impressions of scientific and applied psychology. Participants (N = 112) were randomly assigned to one of six experimental conditions: active groups receiving negative, positive, or no feedback, or passive groups receiving negative, positive, or no feedback. Following participation, participants completed measures of impressions of psychotherapy and psychotherapists, researchers, and instructors. The manipulation did not affect attitudes toward psychology on any of the dependent measures, although gender effects resulted on one measure. Participants in general reported very positive attitudes toward the science and practice of psychology. Recommendations are offered for future research on the effects of more extensive deceptions.


Signal averaged ECG in different patterns of left ventricular hypertrophy and geometry in hypertension.
It is still unknown which factors determine the presence of ventricular late potentials (LP) in hypertension. To evaluate the prevalence of LP in hypertension in relation to the pattern of left ventricular hypertrophy (LVH) and geometry, and to establish the factors causing signal-averaged ECG abnormalities. The study group consisted of 109 patients (58 females, 51 males, mean age 49.7 +/-9.1 years) with hypertension and without coronary artery disease. Two-dimensional Echo Doppler, 24-hr ECG Holter, signal-averaged ECG and spectral analysis of heart rate variability (HRV) were performed. Four patterns of LVH and geometry were identified: normal geometry (N; n=30), concentric remodelling (CR; n=24), concentric hypertrophy (CH; n=38) and eccentric hypertrophy (EH; n=17). LP were more frequently detected in patients with LVH (9.1%), particularly in those with EH, than in patients without LVH (5.6%). Linear regression analysis revealed no correlation between signal-averaged ECG parameters and LV ejection fraction (LVEF) or diastolic LV function indices. None of echocardiographic variables correlated with signalaveraged QRS duration, however, a significant positive correlation between LAS and LV mass (LVM) (r=0.26), LAS and LV end-diastolic volume (EDV) (r=0.2), as well as a significant negative correlation between V40 and LVM (r=-0.22) were noted. A significant positive correlation between LF/HF and signal-averaged QRS (r=0.31) and LAS (r=0.29) as well as a significant negative correlation between LF/HF and V40 (r=-0.21) were found. In the univariate analysis, the presence of EH was significantly related to the occurrence of LP (p<0.01). The reduction of HF power <113 ms(2), indicating a withdrawal of parasympathetic activity, was associated with LP (p<0.05). A ratio of LF 1n/HF 1n >1.28, indicating relative sympathetic overactivity, was a relative risk for LP incidence (p<0.05). In the multivariate analysis, however, all these factors were not independent predictors of the presence of LP. LP are more frequently detected in hypertensives with LVH, particularly in those with eccentric hypertrophy pattern. Left ventricular structural remodelling and withdrawal of parasympathetic tone are the significant determinants of LP occurrence.


Hominid cranial bone structure: a histological study of Omo 1 specimens from Ethiopia using different microscopic techniques.
The microstructure of a hominid cranial vault has not previously been studied to determine its tissue histology, and differences in comparison with that of modern humans. We selected the parietals of Omo-Kibish 1, regarded as one of the oldest (about 130,000 years old) anatomically modern humans, and Omo 1 (Howell), which is a very recent human (about 2,000 years old)-both from the same area of Ethiopia. A combination of macrophotography, polarizing microscopy in the incident and transmission illumination mode, and confocal laser scanning microscopy (CLSM) was employed to examine thin sections, as well as polished and unpolished block faces of unembedded bone fragments, to minimize specimen destruction as much as possible. The methods enabled remarkably detailed information on bone microstructure and remodeling to be gleaned from tiny fragments of bone. The best method for examining fossilized human bones was shown to be that of incident light microscopy, which was the least destructive while producing the most amount of information. Unless the above methods are used, bone-filling minerals, such as calcite, can cause erroneous estimations of bone thickness, as observations with the naked eye or even a magnifying glass cannot determine the limit between the cortex and the diploe. This is particularly important for sciences such as paleoanthropology, in which, for instance, a thick cranial bone of Homo erectus may be confused with a pathological one of H. sapiens and vice versa. Cross sections of parietal bones revealed differences between Omo-Kibish 1 and Omo 1 (Howell) in diploic histology and in the relative thickness between the cortex and diploe, with the former specimen having an H. erectus ratio despite its H. sapiens gross anatomy. Omo-Kibish 1 may still retain some affinities with H. erectus despite its being classified as H. sapiens. Newly described histological structures, such as the reverse type II osteons, the multicanalled osteons, and the osteocytomata are presented here. A modern human skeletal anatomy does not necessarily imply a modern human cranial bone histology. The outer circumferential lamellae of cranial bones are in essence growth lines. Cranial histology of hominids may provide useful information concerning their taxonomy and life history, including such factors as growth rate, developmental stress, and diet.


Pain with no cause! Nurses' perception.
Nurses are called upon to assess chronic pain in health settings and their perceptions about chronic pain are likely to influence the pain assessment and pain relief. This survey as a part of chronic pain education workshop was conducted at National Institute of Mental Health and Neurosciences, Bangalore, India, by pain education group. Here we present the observations collected during the workshop on chronic pain held for nurses. A semiqualitative method was used to survey the perceptions about chronic pain among nurses. The survey form consisted of 28 statements about chronic pain with options of agree and disagree to be marked prepared by the pain education group. The data were computed and frequency distribution of different statements was derived. The total number of participants was 44. Two-thirds of the nurses had good knowledge about pain behaviors. About 70% of the nurses reported that severity of pain to be assessed by observing patient's behavior and felt that if a house wife complains of pain it is to avoid work. Only 11% of the nurses provided correct responses related to discussion on pain being psychological; 90% had poor knowledge about pain communication on pain to be treated only for the underlying cause. These observations highlight the fact that inadequacies in knowledge about chronic pain exist among nurses; the main areas include pain communication and pain treatments. It is important to include proper pain curriculum and training for chronic pain assessment and management.


Micro-RNAs as Potential Predictors of Response to Breast Cancer Systemic Therapy: Future Clinical Implications.
Despite advances in diagnosis and new treatments such as targeted therapies, breast cancer (BC) is still the most prevalent tumor in women worldwide and the leading cause of death. The principal obstacle for successful BC treatment is the acquired or de novo resistance of the tumors to the systemic therapy (chemotherapy, endocrine, and targeted therapies) that patients receive. In the era of personalized treatment, several studies have focused on the search for biomarkers capable of predicting the response to this therapy; microRNAs (miRNAs) stand out among these markers due to their broad spectrum or potential clinical applications. miRNAs are conserved small non-coding RNAs that act as negative regulators of gene expression playing an important role in several cellular processes, such as cell proliferation, autophagy, genomic stability, and apoptosis. We reviewed recent data that describe the role of miRNAs as potential predictors of response to systemic treatments in BC. Furthermore, upon analyzing the collected published information, we noticed that the overexpression of miR-155, miR-222, miR-125b, and miR-21 predicts the resistance to the most common systemic treatments; nonetheless, the function of these particular miRNAs must be carefully studied and further analyses are still necessary to increase knowledge about their role and future potential clinical uses in BC.


[An autopsy case with a combination of hepatocellular carcinoma and cholangiocellular carcinoma].
A 68-year-old male was admitted to the Kurume University Hospital with a diagnosis of hepatocellular carcinoma (HCC). Serum CEA levels ranged from 3.7 ng/ml and 6.8 ng/ml during the course. Serum AFP levels were at normal range at admission and elevated to 13,250 ng/ml 3 months before death. He died of liver failure 17 months after admission. An autopsy disclosed diffuse infiltrative tumors distributed throughout the liver with metastasis to the bilateral lungs. Histologically, tumors of the liver consisted of elements of both HCC and cholangiolocellular carcinoma. Cholangiolocellular carcinoma is believed to occur from the canals of Hering or cholangiole, and this case may provide further information as to the histogenesis of combined HCC and cholangiocarcinoma.


Effect of high-pressure-induced ice I-to-ice III phase transitions on inactivation of Listeria innocua in frozen suspension.
The inactivation of Listeria innocua BGA 3532 at subzero temperatures and pressures up to 400 MPa in buffer solution was studied to examine the impact of high-pressure treatments on bacteria in frozen matrices. The state of aggregation of water was taken into account. The inactivation was progressing rapidly during pressure holding under liquid conditions, whereas in the ice phases, extended pressure holding times had comparatively little effect. The transient phase change of ice I to other ice polymorphs (ice II or ice III) during pressure cycles above 200 MPa resulted in an inactivation of about 3 log cycles, probably due to the mechanical stress associated with the phase transition. This effect was independent of the applied pressure holding time. Flow cytometric analyses supported the assumption of different mechanisms of inactivation of L. innocua in the liquid phase and ice I (large fraction of sublethally damaged cells due to pressure inactivation) in contrast to cells subjected to ice I-to-ice III phase transitions (complete inactivation due to cell rupture). Possible applications of high-pressure-induced phase transitions include cell disintegration for the recovery of intracellular components and inactivation of microorganisms in frozen food.


Rapid decrease of intracellular pH associated with inhibition of Na+/H+ exchanger precedes apoptotic events in the MNK45 and MNK74 gastric cancer cell lines treated with 2-aminophenoxazine-3-one.
The effects of Phx-3 on changes in intracellular pH (pHi) in the MKN45 and MKN74 human gastric cancer cell lines were evaluated in order to determine the mechanism for the proapoptotic effects of 2-aminophenoxazine-3-one (Phx-3) on these cells. Phx-3 (100 μM) reduced pHi in MKN45 from 7.45 to 5.8, and in MKN74 from 7.5 to 6.2 within 1 min of engagement with these cells. Such a decrease of pHi was closely correlated with the dose of this phenoxazine and continued for 4 h. The activity of Na+/H+ exchanger isoform l (NHE1), which is involved in H+ extrusion from the cells, was dose-dependently suppressed by Phx-3 in these cells, and was greatly suppressed in the presence of 100 μM Phx-3. This result indicates that the decrease of pHi in MKN45 and MKN74 cells is closely associated with the inhibition of NHE1 in these cells. The morphology of these cells at 24 h after treatment with Phx-3 indicated shrinkage of the cells and condensation of the nuclear chromatin structure, which are characteristic of the apoptotic events in these gastric cancer cells. Cytotoxicity of Phx-3 against MKN45 and MKN74 cells was extensive because almost all MKN45 cells lost viability at 24 h in the presence of 20 μM Phx-3, and nearly 50% of the MKN74 cells lost viability in the presence of 50 μM Phx-3. These results suggest that rapid and extensive decrease of pHi in human gastric cancer MKN45 and MKN74 cells caused by Phx-3 might disturb intracellular homeostasis, leading to apoptotic and cytotoxic events in these cells. Phx-3 is a good candidate for therapeutics of gastric cancer that is intractable to conventional chemopreventive therapies.


[Effect of electroacupuncture intervention on renal function and expression of renal beta-catenin in rats with chronic renal failure].
To observe the effect of electroacupuncture (EA) intervention on renal function and expression of renal beta-catenin in rats with chronic renal failure (CRF), so as to reveal its mechanism underlying improvement of CRF. Male SD rats were randomly divided into normal, model and EA groups, with 10 rats in each group. CRF model was induced by feeding the rats with 0.5% Adenine(100 mg/d, in forage) for 21 days. EA (1-3 mA, 1.5-2 Hz) was applied to bilateral "San-yinjiao" (SP 6), "Taixi" (KI 3) and "Shenshu" (BL 23) for 20 min, once daily for 30 days. Serum creatinine (Scr) and blood urine nitrogen (BUN) contents were assayed by enzymatic method and deoxy enzymatic method, respectively, and the expression of p-catenin protein in the renal tissue was determined by Western blot. Following modeling, serum Scr and BUN contents and renal p-catenin protein expression level were significantly increased in the model group in comparison with those of the normal group (P<0.05). After EA intervention, serum Scr and BUN contents and the expression of beta-catenin in the renal tissue were all significantly decreased in the EA group compared to the model group (P<0.05). In addition, the animals' body weight values of both model and EA groups were apparently lower than those of the normal group before EA treatment (P<0.05). After EA intervention, the body weight values of the EA group were markedly higher than those of the model group in spite of being still lower than normal rats (P<0.05). EA can effectively suppress CRF-induced increase of serum Scr and BUN contents and renal beta-catenin protein expression in CRF rats, suggesting an improvement of the renal function after EA intervention by reducing the expression of beta-catenin in the renal tissue.


[Role of the second look in ovarian neoplasia].
The indications for the execution of a second look in patients affected with ovarian cancers and the possible benefits of this procedure, related to the stage of the neoplastic disease, are examined. The second look, at first largely used in patients in which had been performed adjuvant chemotherapy with drugs containing platinum and with no evidence of residual disease, has been later strongly criticized and the effective usefulness of this invasive procedure discussed. At the moment, we think that the indications for its execution are still large because with the second look it is also possible to put into the abdomen a catheter which can be used for locoregional chemotherapy and there is now the opportunity to perform this procedure also in video-laparoscopy.


Efficacy of measuring visual performance of LASIK patients under photopic and mesopic conditions.
The aim of the study was to compare the visual performance of LASIK eyes measured using high-contrast logMAR letter charts under bright (photopic) and dim (mesopic) conditions. A total of 46 subjects (35 +/- 8 years of age) undergoing LASIK procedures were recruited for the study. The best spectacle-corrected visual acuity (BSCVA) of each subject was measured using the high-contrast ETDRS logMAR chart under photopic and mesopic conditions at 3 visits: preoperative (Pre), 1 month postoperative (Post1) and 3 months postoperative (Post3). The differences in logMAR scores for the right eyes only were analysed for the Pre-Post1 (n = 46), Pre-Post3 (n = 18) and Post1-Post3 (n = 16) comparisons. The logMAR scores of subjects were worse at the 1-month postoperative visit than preoperatively, and improvement in visual performance was seen at the 3-month postoperative visit. These changes in visual performance became more evident under mesopic conditions. The means and standard errors of the differences in logMAR scores for the Pre-Post3 (0.097 +/- 0.020) were slightly larger than those of the Pre-Post1 (-0.067 +/- 0.019) and Post1-Post3 (0.031 +/- 0.012) comparisons. Under mesopic conditions, the visual performance of the subjects was statistically significant for the 3 comparisons, but not under photopic conditions. High-contrast logMAR chart performed under mesopic conditions has the potential to replace visual acuity measured under photopic conditions in providing more reliable representation of postoperative visual outcomes of LASIK eyes. Eye doctors should consider performing this vision test routinely to gauge the success of LASIK surgery.


Protein kinase C inhibits epidermal growth factor-dependent tyrosine phosphorylation of phospholipase C gamma and activation of phosphoinositide hydrolysis.
Recent studies have shown that the receptor for epidermal growth factor (EGF) can associate with and tyrosine-phosphorylate the gamma-isozyme of phosphoinositide (PtdIns)-specific phospholipase C (PLC gamma), suggesting a possible mechanism for activation of PtdIns hydrolysis by EGF. In the present study, the coupling between PtdIns hydrolysis and PLC gamma tyrosine phosphorylation in WB liver epithelial cells was examined. Peak levels of [P-Tyr]PLC gamma, measured by anti-P-Tyr immunoblotting, occurred at 0.5-2 min of EGF treatment and coincided with the onset of [3H]inositol phosphate production. The termination of PtdIns hydrolysis after EGF stimulation was accompanied by return of [P-Tyr]PLC gamma to near-basal levels. Activation of protein kinase C (PKC) with a phorbol ester inhibited (IC50 = 3-10 nM) both EGF-dependent PtdIns hydrolysis and PLC gamma phosphorylation by more than 90%. Both EGF-stimulated responses were potentiated in cells depleted of PKC by prolonged phorbol ester treatment. At physiological ionic strength, monoclonal antibodies to PLC gamma specifically precipitated (in addition to PLC gamma) the EGF receptor and at least six other [P-Tyr]proteins from extracts of EGF-treated cells. PKC activation had differential effects on the tyrosine phosphorylation of these coprecipitating proteins, i.e. the relative abundance of certain [P-Tyr] proteins decreased, whereas that of another protein increased. In conclusion, EGF-stimulated tyrosine phosphorylation of PLC gamma is broadly correlated with stimulation of PtdIns hydrolysis, consistent with a role for tyrosine phosphorylation in PLC activation. The attendant diacylglycerol release and activation of PKC may terminate PLC gamma activation, in part by inhibiting PLC gamma phosphorylation by the EGF receptor. Our results suggest further that PKC may exert regulatory effects by altering the relationship of PLC gamma to its associated [P-Tyr]proteins.


Excited state dynamics of aniline homoclusters.
We have investigated the relaxation, following excitation in the 290-235 nm region, of neutral aniline homoclusters (An)n formed in a supersonic expansion by femtosecond time resolved ionization. The applied method permits isolation of the dynamics of the dimer from that originated in bigger species of the generated distribution. Interestingly, and differently from the monomer and (An)n≥3 clusters, the dimer does not present a N-H dissociative 1πσ* channel. This fact can be explained in terms of the symmetric structure adopted, in which each molecule establishes two N-Hπ interactions, destabilizing the H dissociation channel. The observations permit relating the photophysics to the interactions established by the aniline units and confirming previous observations and theoretical predictions on the structure of aniline aggregates.


In silico discovery and in vitro activity of inhibitors against Mycobacterium tuberculosis 7,8-diaminopelargonic acid synthase (Mtb BioA).
Computer-aided drug discovery and development approaches such as virtual screening, molecular docking, and in silico drug property calculations have been utilized in this effort to discover new lead compounds against tuberculosis. The enzyme 7,8-diaminopelargonic acid aminotransferase (BioA) in Mycobacterium tuberculosis (Mtb), primarily involved in the lipid biosynthesis pathway, was chosen as the drug target due to the fact that humans are not capable of synthesizing biotin endogenously. The computational screening of 4.5 million compounds from the Enamine REAL database has ultimately yielded 45 high-scoring, high-affinity compounds with desirable in silico absorption, distribution, metabolism, excretion, and toxicity properties. Seventeen of the 45 compounds were subjected to bioactivity validation using the resazurin microtiter assay. Among the 4 actives, compound 7 ((Z)-N-(2-isopropoxyphenyl)-2-oxo-2-((3-(trifluoromethyl)cyclohexyl)amino)acetimidic acid) displayed inhibitory activity up to 83% at 10 μg/mL concentration against the growth of the Mtb H37Ra strain.


Custom Acetabular Cages Offer Stable Fixation and Improved Hip Scores for Revision THA With Severe Bone Defects.
Revision THA is particularly challenging in hips with severe acetabular bone loss. When the extent or geometry of the acetabular bone loss precludes more-straightforward techniques such as jumbo hemispheric cementless shells, reconstruction with morselized allograft protected by a custom cage may offer an alternative, but, to our knowledge, few series have reported on results with this approach. For patients with severe (Paprosky IIIB) defects, we asked: do individualized custom cages result in (1) improved Harris hip scores; (2) restoration of hip center; and (3) a low incidence of surgical complications? Twenty-six patients (26 hips) with a massive acetabular defect were involved in this study from 2003 to 2013. During this period, one patient was lost to followup and one died, leaving 24 patients (eight males, 16 females) in this retrospective analysis. The customized cages were individualized to each patient's bone defect based on rapid-prototype three-dimensional printed models. Mean followup was 67 months (range, 24-120 months). Harris hip scores were assessed before surgery and at each followup. Postoperative radiographs were evaluated for cage position, migration, and graft incorporation. Complications and reoperations were assessed by chart review. The mean Harris hip score improved from 36 (SD, 8; range, 20-49) to 82 (SD, 18; range, 60-96) (p < 0.001). Individualized custom cages resulted in generally reliable restoration of the hip center. No rerevisions have been performed. None of the cups showed radiographic migration, but one cage was believed to be loose, based on a circumferential 2-mm radiolucent line. Cancellous allografts appeared to be incorporated in 23 of 24 patients. One deep infection and one superficial infection were observed and treated with irrigation, débridement, and vacuum-sealing drainage. One dislocation and one suspected injury of the superior gluteal nerve also were observed and treated conservatively. Individualized custom cages using rapid prototyping and three-dimensional printing appeared to provide stable fixation and improved hip scores at short-term followup in this small, single-center series. As further improvements in the design and manufacturing process are made, future studies should evaluate larger patient groups for longer times, and, ideally, compare this approach with alternatives for these complex bone defects. Level IV, therapeutic study.


Study of PLGA microspheres loaded with pOsx/PEI nanoparticles for repairing bone defects in vivo and in vitro.
Autogenous or allogenic bone transplantation is the main treatment for bone defects and nonunions. However, the shortcomings of autogenous or allogenic bone transplantation limit its wide application in clinical use. This study investigated the effect of poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with pOsterix (pOsx)/polyethylenimine (PEI) nanoparticles in repairing bone defects and explored its mechanism. Poly(lactic-co-glycolic acid) microspheres loaded with pOsx/PEI nanoparticles were constructed. The Osx transfection effect was detected by fluorescence quantitative PCR and western blotting methods. 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-diphenytetrazoliumromide (MTT) and flow cytometry methods were used to detect cell proliferation. The collagen I (Col-1), osteopontin (OPN) and osteocalcin (OC) expression levels were detected using real-time polymerase chain reaction (RT-PCR) and western blotting methods. Bone defect model was constructed. Bone repair was detected using X-ray, hematoxylin and eosin (H&E) staining, and Mason staining methods. PLGA@pOsx/PEI has transfection effect both in vitro and in vivo, does not affect cell proliferation and is safe for cells. PLGA@pOsx/PEI could promote the expression of Col-1, OPN and OC in vitro and in vivo. PLGA@pOsx/PEI could promote osteogenesis in vivo. PLGA@pOsx/PEI with high Osx expression could promote the expression of OC, OPN, and COL-I. PLGA@pOsx/PEI can be used as a material for repairing bone defects and can promote bone formation. These results provide a theoretical and practical basis for its further clinical application.


Association between napping and 24-hour blood pressure variability among university students: A pilot study.
Blood pressure variability (BPV) has been reported to be a predictor of cardiovascular and some cognitive diseases. However, the association between napping and BPV remains unknown. This study aimed to explore the association between napping and BPV. A cross-sectional study including 105 university students was conducted. Participants' 24 h ambulatory blood pressure monitoring (24 h ABPM) were measured, and napping behaviors were investigated. BPV were measured by the 24 h ABPM, included standard deviation (SD), coefficient of variation (CV), and average real variability (ARV). Among the participants, 61.9% reported daytime napping. We found that nap duration was significantly associated with daytime CV of diastolic blood pressure (DBP) (r = 0.250, P = 0.010), nighttime CV of systolic blood pressure (SBP) (r = 0.217, P = 0.026), 24 h WCV of DBP (r = 0.238, P = 0.014), 24 h ARV of SBP (r = 0.246, P = 0.011) and 24 h ARV of DBP (r = 0.291, P = 0.003). Compared with the no napping group, 24 h WCV of DBP, daytime CV of DBP, and daytime SD of DBP were significantly higher in participants with napping duration >60 min. With multiple regression analysis we found that nap duration was an independent predictor for 24 h ARV of SBP (β = 0.859, 95% CI, 0.101-1.616, P = 0.027) and 24 h ARV of DBP (β = 0.674, 95% CI, 0.173-1.175, P = 0.009). Napping durations are associated with BPV among university students. Especially those with napping durations >60 min had a significantly higher BPV than those non-nappers.


Hemoglobin Koya Dora: high frequency of a chain termination mutant.
Approximately 10% of the members of the Koya Dora tribe from Andhra Pradesh (India) carry an alpha chain hemoglobin variant, Hb Koya Dora (Hb KD), usually in amounts of 0.5%-2% of total hemoglobin. In four presumed homozygotes for Hb KD, up to 10% of the abnormal hemoglobin was present. The alpha chain of Hb KD was found to be elongated by at least 16 residues, possibly as a result of a mutation of the normal alpha chain termination codon UAA TO UCA, coding for serine. A pedigree in which two individuals possess Hb KD as well as the alpha chain variant Hb Rampa and normal Hb A proves the existence of two alpha chain loci in this population. Hb DK resembles the previously described Hb Constant Spring [6, 7] in many aspects, probably also in its alpha thalassemia-like expression.


Risk-Factor Profile and Comorbidities in 2398 Patients With Newly Diagnosed Hypertension From the Abuja Heart Study.
Risk factors, comorbidities, and end-organ damage in newly diagnosed hypertension (HT) are poorly described in larger cohorts of urban African patients undergoing epidemiological transition. We therefore decided to characterize a large cohort of hypertensive subjects presenting to a tertiary health center in sub-Saharan Africa. It is an observational cross-sectional study. We prospectively collected detailed clinical, biochemical, electrocardiography, and echocardiography data of all subjects with HT as the primary diagnosis in patients presenting at the Cardiology Unit of the University of Abuja Teaching Hospital over an 8-year period. Of 2398 subjects, 1187 patients (49.4%) were female with a mean age of 51 ± 12.8 years. Presenting symptoms and signs were most commonly palpitation in 691 (28.8%) followed by dyspnoea on exertion in 541 (22.6%), orthopnea in 532 (22.2%), pedal oedema in 468 (19.5%), paroxysmal nocturnal dyspnoea in 332 (13.8%), whereas only 31 (1.3%) presented with chest pain. Risk factors were obesity in 671 (28%); 523 (21.8%) had total cholesterol >5.2 mmol/L, diabetes mellitus was present in 201 (8.4%) and 187 (7.8%) were smokers. End-organ damage was present in form of echocardiographic left ventricular hypertrophy in 1336 (55.7%) followed by heart failure in 542 (22.6%). Arrhythmias occurred in 110 (4.6%) of cases, cerebrovascular accident in 103 (4.3%), chronic kidney disease in 26 (1.1%), hypertensive encephalopathy in 10 (0.4%), and coronary artery disease in 6 (0.26%). There were marked differences in sex as women were more obese and men presented with more advanced disease. The burden of HT and its complications in this carefully characterized African cohort is quite enormous with more than three-fourth having one form of complication. The need of effective primary and secondary preventive measures to be mapped out to tackle this problem cannot be overemphasized.


Gonadotropin pulsations across development.
Initiation and maintenance of the reproductive axis in the human is contingent upon the pulsatile secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus. In man, tracking endogenous GnRH secretion relies on frequent peripheral sampling of three glycoprotein products of the gonadotrope, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and free alpha-subunit (FAS). FAS is superior to LH as a surrogate marker of GnRH secretory dynamics in those circumstances where GnRH secretion is rapid or where the pituitary LH response is low. The pattern of GnRH secretion is constantly changing across development; from high levels during the neonatal period, through a period of quiescence in mid-childhood, followed by sleep-entrained reactivation of the reproductive axis at the onset of puberty, ultimately culminating in the adult pattern of pulsatile secretion which in the male is approximately every 2 h and in the female varies with the stage of the menstrual cycle. This episodic mode of secretion allows differential impact of feedback mechanisms on the GnRH neurons and facilitates the maintenance of the reproductive axis during periods of stress by allowing frequency and amplitude modulations.


An interventional model to develop health professionals in West Africa.
The health sector is characterized by a human resource base lacking in numbers, specialized skills, and management skills. West African Health Organization (WAHO) recognizes the need within the West Africa sub-region for bilingual professionals who are skilled in public health, management, leadership, and information technology to build human capacity in public health and developed the Young Professionals Internship Program (YPIP). Our study explores the evolution of the programme. YPIP program has successfully carried out its original aims and objectives to equip young professionals with basic principles of public health, management, and leadership, acquire competence in a second official language (French, English, and Portuguese), information and communication technology. Contributing factors towards this successful evaluation included positive ratings and commentary from previous interns about the relevance, usefulness, and quality of the programme, encouraging feedback from WAHO management, trainers, administrators, and intern employers on the impact of the YPIP program on young professionals, supporting evidence that demonstrates increased knowledge in professional skills and language competency.


Evaluation of the proliferation and differentiation behaviors of mesenchymal stem cells with partially converted borate glass containing different amounts of strontium in vitro.
The objective of this study was to examine the proliferation and differentiation behaviors of different compositions of strontium-containing (from 0-12 mol%) borate glasses with mesenchymal stem cells (MSCs). The Cell Counting Kit-8 (CCK-8) assay revealed that after three days of culturing, the 6Sr group had the highest cell growth rate. Analysis of cell morphology revealed that cells proliferated well near the particles of the samples in all the groups on day 3. On day 7, cells in the 6Sr group demonstrated a higher proliferation rate than other 4 groups under the microscope. When performing the Live-Dead staining experiment, the 6Sr group had the least number of dead cells. Total DNA qualification indicated that the 6Sr group had a statistically higher concentration compared with the remaining groups. It was found that on day 7, compared with the 0Sr group, the core binding factor α1 (Cbfa1) mRNA expression level was significantly higher in the 6Sr, 9Sr and 12Sr groups. On day 14, compared with the 0Sr group, the bone sialoprotein (BSP) mRNA level was significantly higher in the 6Sr group. Additionally, on day 21, the 6Sr and 9Sr groups demonstrated higher osteocalcin (OCN) mRNA expression levels compared with the 0Sr group. In the alkaline phosphatase (ALP) activity test, on day 21, the 6Sr group presented a higher activity than the 0Sr group. Further, the number of mineralized nodules per unit in MSCs was measured by Alizarin Red S staining. The results showed that the 6Sr and 9Sr groups had the greatest number of mineralized nodules. Therefore, it could be concluded that borate glasses containing strontium oxide of 0, 3, 6, 9 and 12 mol% demonstrate a significant level of proliferation when interacting with MSCs. The borate glass containing 6 mol% strontium oxide had the greatest level of proliferation when cultured with MSCs. The borate glass containing 6 and 9 mol% strontium oxide facilitated an improved bone formation ability compared with the remaining two compositions.


Inconsistent Denoising and Clustering Algorithms for Amplicon Sequence Data.
Natural microbial communities have been studied for decades using the 16S rRNA gene as a marker. In recent years, the application of second-generation sequencing technologies has revolutionized our understanding of the structure and function of microbial communities in complex environments. Using these highly parallel techniques, a detailed description of community characteristics are constructed, and even the rare biosphere can be detected. The new approaches carry numerous advantages and lack many features that skewed the results using traditional techniques, but we are still facing serious bias, and the lack of reliable comparability of produced results. Here, we contrasted publicly available amplicon sequence data analysis algorithms by using two different data sets, one with defined clone-based structure, and one with food spoilage community with well-studied communities. We aimed to assess which software and parameters produce results that resemble the benchmark community best, how large differences can be detected between methods, and whether these differences are statistically significant. The results suggest that commonly accepted denoising and clustering methods used in different combinations produce significantly different outcome: clustering method impacts greatly on the number of operational taxonomic units (OTUs) and denoising algorithm influences more on taxonomic affiliations. The magnitude of the OTU number difference was up to 40-fold and the disparity between results seemed highly dependent on the community structure and diversity. Statistically significant differences in taxonomies between methods were seen even at phylum level. However, the application of effective denoising method seemed to even out the differences produced by clustering.


FACTORS ASSOCIATED WITH THE UPTAKE OF SODIUM DICHLOROISOCYANURATE (NADCC) TABLETS AS HOUSEHOLD WATER-TREATMENT PRODUCT AMONG CAREGIVERS OF CHILDREN UNDER FIVE IN BENIN, WEST AFRICA.
Improving access to safe drinking water is a critical step in mitigating diarrheal diseases that affect millions of children under 5 years throughout the developing world each year. While the delivery of safe water is out of the reach of many countries, the utilization of Sodium dichloroisocyanurate (NaDCC) is a proven cost-effective alternative to prevent diarrhea caused by waterborne pathogens. However, its uptake remains low in many developing countries, such as the Republic of Benin. This study examines the trends and the determinants of NaDCC uptake in Benin. Population Services International and its affiliate conducted two multistage household surveys among caregivers of children under five in Benin to examine the practices towards diarrheal disease in children under five and identify the factors associated with the use of NaDCC in this population. 2912 respondents/caregivers of children under five were interviewed in 2009 versus 3196 in 2011. The proportion of caregivers who reported ever treating water with NaDCC increased from 5.8% in 2009 to 11.5% in 2011, p < 0.001. The logistic regression model showed that caregivers who knew places that sell NaDCC in the community; those who felt capable of utilizing NADCC correctly to treat drinking water as well as caregivers who reported to be Muslim were more likely than their counterparts to use NaDCC as water treatment product. In order to increase the use of NADCC among caregivers, the Government of Benin and its development partners should focus not only on making NADCC available in the community and informing the community members about the different points of sale, but also in building up the capacity and confidence of caregivers in utilizing it.


Pulmonary alveolar proteinosis in a patient with chronic myelogenous leukemia.
We describe the case of a 53-year-old Philadelphia-chromosome-positive woman with chronic myelogenous leukemia, who developed pulmonary alveolar proteinosis (PAP). The possible mechanism involved in the pathogenesis of PAP are discussed based on the clinical and laboratory data for this patient as well as on experimental and clinical data reported in the literature.


Antipsychotic prescription patterns and associated factors among the elderly with psychiatric illnesses.
Prescribing rate of antipsychotics in elderly patients with psychiatric illnesses has been increasing all over the world. However, there is a lack of research examining the use of antipsychotics at psychiatric hospitals. We aim to find out long-term trends in antipsychotic prescriptions and factors associated with the use of antipsychotics in the elderly population. All outpatient visits with patients aged over 65 years between 2006 and 2015 in a psychiatric hospital were included in the analysis. Demographic and clinical data, including patient age, sex, National Health Insurance status, psychiatric diagnosis and antipsychotic prescription, were retrieved through the electronic medical information system. In this study, we found that prescribing rate of antipsychotics has increased around 5.07% through the study period (from 57.25% in 2006 to 60.15% in 2015, P < 0.001). Among all antipsychotics, there was an increase in the use of second-generation antipsychotics with a simultaneous decline in the use of first-generation antipsychotics. Logistic regression analysis showed advanced age, female gender and certification for catastrophic illnesses were positively associated with the use of antipsychotics. Furthermore, patients most likely to be prescribed an antipsychotic were those with psychotic disorders, followed by dementia, and then affective or neurotic disorders. The results of this study were consistent with the worldwide trend of increasing prescriptions of second-generation antipsychotics among elderly patients with psychiatric illnesses. Despite the potential benefits of these medications on certain psychiatric symptoms, clinicians need to exercise due caution as they may also cause potentially serious side effects among the elderly population.


Microsphaerones A and B, two novel gamma-pyrone derivatives from the sponge-derived fungus Microsphaeropsis sp.
Two new metabolites, microsphaerones A (1) and B (2), were identified from the EtOAc extract of the culture of an undescribed fungus of the genus Microsphaeropsis, isolated from the Mediterranean sponge Aplysina aerophoba. Compounds 1 and 2 represent the first examples of gamma-pyrone derivatives of the fungal genus Microsphaeropsis. The structures of the compounds were elucidated on the basis of comprehensive spectral analysis ((1)H, (13)C, (1)H-(1)H COSY, HMQC, and HMBC NMR, as well as low- and high-resolution ESI and EIMS experiments). The (S)-2-methylsuccinic acid moiety present in 1 was established by GC-MS analysis of a hydrolysis product.


Ambient temperature and cardiovascular biomarkers in a repeated-measure study in healthy adults: A novel biomarker index approach.
Associations of ambient temperature with cardiovascular morbidity and mortality have been well documented in numerous epidemiological studies, but the underlying pathways remain unclear. We investigated whether systemic inflammation, coagulation, systemic oxidative stress, antioxidant activity and endothelial function may be the mechanistic pathways associated with ambient temperature. Forty study participants underwent repeated blood collections for 12 times in Beijing, China in 2010-2011. Ambient temperature and air pollution data were measured in central monitors close to student residences. We created five indices as the sum of weighted biomarker percentiles to represent the overall levels of 15 cardiovascular biomarkers in five pathways (systemic inflammation: hs-CRP, TNF-α and fibrinogen; coagulation: fibrinogen, PAI-1, tPA, vWF and sP-selectin; systemic oxidative stress: Ox-LDL and sCD36: antioxidant activity: EC-SOD and GPX1; and endothelial function: ET-1, E-selectin, ICAM-1 and VCAM-1). We used generalized mixed-effects models to estimate temperature effects controlling for air pollution and other covariates. There were significant decreasing trends in the adjusted means of biomarker indices over the lowest to the highest quartiles of daily temperatures before blood collection. A 10°C decrease at 2-d average daily temperature were associated with increases of 2.5% [95% confidence interval (CI): 0.7, 4.2], 1.6% (95% CI: 0.1, 3.1), 2.7% (95% CI: 0.5, 4.8), 5.5% (95% CI: 3.8, 7.3) and 2.0% (95% CI: 0.3, 3.8) in the indices for systemic inflammation, coagulation, systemic oxidative stress, antioxidant activity and endothelial function, respectively. In contrast, the associations between ambient temperature and individual biomarkers had substantial variation in magnitude and strength. The altered cardiovascular biomarker profiles in healthy adults associated with ambient temperature changes may help explain the temperature-related cardiovascular morbidity and mortality. The biomarker index approach may serve as a novel tool to capture ambient temperature effects.


Structural and functional genetic disorders of the great vessels and outflow tracts.
Development of the aorta and pulmonary artery is a complex process involving multiple molecular genetic pathways that modulate morphogenesis of the outflow tracts and the anastomosis of branch vessels. Recent genetic studies of the cardiovascular system demonstrate that congenital and adult onset progressive disorders of the great vessels such as aneurysms are components of generalized vascular, cardiac, and extracardiovascular syndromes. Current paradigms suggest that aortic disease is founded in patterning anomalies of the conotruncus that occur in utero. These aberrations can be consequences of genetic aberrations in transcriptional regulation of signal transduction both within and outside the developing great vessels.


Mitosis and intermediate-sized filaments in developing skeletal muscle.
A new class of filaments intermediate in diameter between actin and myosin filaments has been demonstrated in skeletal muscle cells cultured from chick embryos. These filaments, which account for the majority of free filaments, average 100 A in diameter. They may run for more than 2 micro in a single section and can be distinguished in size and appearance from the thick and thin filaments assembled into myofibrils. The 100-A filaments are seen scattered throughout the sarcoplasm at all stages of development and show no obvious association with the myofibrils. The 100-A filaments are particularly conspicuous in myotubes fragmented by the mitotic inhibitors, colchicine and Colcemid. In addition, filaments similar in size and appearance to those found in myotubes are present in fibroblasts, chondrocytes, and proliferating mononucleated myoblasts. The 100-A filaments are present in cells arrested in metaphase by mitotic inhibitors. Definitive thick (about 150 A) or thin (about 60 A) myofilaments are not found in skeletal myogenic cells arrested in metaphase. Myogenic cells arrested in metaphase do not bind fluorescein-labeled antibody directed against myosin or actin. For these reasons, it is concluded that not all "thin" filaments in myogenic cells are uniquely associated with myogenesis.


Within-subject coronal caries distribution patterns: an evaluation of randomness with respect to the midline.
The distribution of caries among homologous surfaces can exhibit three possible patterns: random, aggregated, or regular. In a random caries pattern, caries lesions are randomly distributed among homologous surfaces. An aggregated caries pattern is distinguished by the aggregation of lesions on one side of the mouth or the other to a greater extent than would be expected by chance alone. For a regular caries pattern, the left-right distribution of lesions is more homogenous than would be expected by chance alone. A test statistic based on the left-right distribution of caries lesions among discordant homologous pairs was developed to investigate which of these three caries patterns is present in a representative sample of the adult United States population. The data originated from the National Survey of Oral Health in the US (Employed Adults), 1985-1986. Of the 15,132 subjects studied, 12,776 subjects had 2 or more decayed or filled teeth. (At least 2 carious or filled teeth are required for detection of patterns.) Approximately 50% of these subjects (n = 6,439) had two or more discordant homologous tooth pairs. With these tooth pairs, the hypothesis of a random caries pattern was rejected in favor of an aggregated caries pattern (p < 0.0001). Similar findings were obtained with discordant homologous surface pairs. This aggregation of caries on one side of the mouth or the other may be due to genetic, infectious, and/or environmental factors.


Cloning of a single-chain variable fragment (scFv) switching active plasminogen activator inhibitor-1 to substrate.
Increased levels of plasminogen activator inhibitor-1 (PAI-1) are a well-known risk for cardiovascular diseases. A significant number of investigations are aimed at lowering plasma levels of PAI-1 to enhance endogenous fibrinolysis. We have recently generated monoclonal antibodies that neutralize PAI-1 activity by switching the inhibitory conformation to a substrate conformation. However, intact murine antibodies have quite some disadvantages for therapeutic use in man. In the current study, we describe the construction of a smaller antibody fragment derived from a monoclonal antibody (MA-8H9D4) with PAI-1 neutralizing properties. The cDNAs encoding the variable domains of the heavy and light chain were amplified, linked and cloned into a phagemid vector. Resulting clones were expressed as a single-chain variable fragment (scFv, VH-(Gly4Ser)3-VL) on the surface of a phage and selected for binding to PAI-1. Subsequently, a positive phage was used for the production of soluble scFv-8H9D4. Following purification, the characteristics of the scFv-8H9D4 were compared to those of the original MA-8H9D4. The scFv inhibited PAI-1 activity to a similar extent as MA-8H9D4 and by a similar mechanism, i.e., induction of a conformational switch. Thus, this smaller antibody fragment, exhibiting the same properties as the parent molecule may constitute a useful starting point for the design of PAI-1 neutralizing therapeutics.


Seronegative Neuromyelitis Optica Spectrum Disorder: An Unusual Presentation of Acute Brainstem Syndrome.
BACKGROUND Neuromyelitis optica (NMO) is an autoimmune, demyelinating, inflammatory disorder affecting the central nervous system, mostly targeting optic nerves and the spinal cord. NMO spectrum disorder (NMOSD) is a newly revised nomenclature in which new diagnostic criteria have been developed, including serological testing of serum aquaporin-4 immunoglobulin G (AQP4-IgG) antibodies. Results of a negative antibody will group the patient in a seronegative subgroup. CASE REPORT We describe the case of a 27-year-old female who presented to our hospital with new onset of sudden unexplained vomiting, dysphagia, dysphonia, and food regurgitation. Extensive investigations were done and brain magnetic resonance imaging (MRI) showed a small nonspecific area of signal abnormality in the right dorsal medulla. Aquaporin-4 antibodies were negative, and the patient was diagnosed with seronegative NMOSD with acute brainstem syndrome after meeting the diagnostic criteria. The patient's condition improved after steroids administration. CONCLUSIONS We report an unusual presentation of seronegative NMOSD presenting with acute brainstem syndrome.


Ultrasound diagnosis of gastro-oesophageal reflux.
A method of diagnosing gastro-oesophageal reflux using ultrasound is described. This method was compared with barium swallow examination in 20 patients and found to be as accurate in infants and young children.


Gene expression and cellular localization of ROMKs in the gills and kidney of Mozambique tilapia acclimated to fresh water with high potassium concentration.
Regulation of plasma K(+) levels in narrow ranges is vital to vertebrate animals. Since seawater (SW) teleosts are loaded with excess K(+), they constantly excrete K(+) from the gills. However, the K(+) regulatory mechanisms in freshwater (FW)-acclimated teleosts are still unclear. We aimed to identify the possible K(+) regulatory mechanisms in the gills and kidney, the two major osmoregulatory organs, of FW-acclimated Mozambique tilapia (Oreochromis mossambicus). As a potential molecular candidate for renal K(+) handling, a putative renal outer medullary K(+) channel (ROMK) was cloned from the tilapia kidney and tentatively named "ROMKb"; another ROMK previously cloned from the tilapia gills was thus renamed "ROMKa". The fish were acclimated to control FW or to high-K(+) (H-K) FW for 1 wk, and we assessed physiological responses of tilapia to H-K treatment. As a result, urinary K(+) levels were slightly higher in H-K fish, implying a role of the kidney in K(+) excretion. However, the mRNA expression levels of both ROMKa and ROMKb were very low in the kidney, while that of K(+)/Cl(-) cotransporter 1 (KCC1) was robust. In the gills, ROMKa mRNA was markedly upregulated in H-K fish. Immunofluorescence staining showed that branchial ROMKa was expressed at the apical membrane of type I and type III ionocytes, and the ROMKa immunosignals were more intense in H-K fish than in control fish. The present study suggests that branchial ROMKa takes a central role for K(+) regulation in FW conditions and that K(+) excretion via the gills is activated irrespective of environmental salinity.


[Metal-on-metal hip arthroplasty].
In Denmark 4,456 metal-on-metal (MoM) hip prostheses have been implanted. Evidence demonstrates that some patients develope adverse biological reactions causing failures of MoM hip arthroplasty. Some reactions might be systemic. Failure rates are associated with the type and the design of the MoM hip implant. A Danish surveillance programme has been initiated addressing these problems.


Duplex real-time PCR assays for rapid detection of virulence genes in E. coli isolated from post-weaning pigs and calves with diarrhoea.
Duplex real-time PCR assays were used as modules to cover partially automated detection of 12 genes encoding adhesins, enterotoxins and Shiga toxins in faecal E. coli isolates. For this a total of 194 E. coli isolates from pigs suffering from post-weaning diarrhoea (PWD), including 65 isolates with haemolytic activity, and 83 isolates from calves with diarrhoea were examined. Data obtained by PCR were compared with O-typing and with haemolytic activity as indirect virulence markers. E. coli O-types O139:K82, O141:K85, and O149:K91 accounted for 43.8% (n = 85) of all porcine strains and for 55.4% (n = 36) of the porcine strains, which exhibited haemolytic activity. These strains carried virulence genes by 65.9% (n = 56) and 80.6% (haemolytic E. coli, n = 29), respectively. The E. coli O-types O139:K82 and O141:K85 were significantly associated with the adhesin gene F18, and O149:K81 with the F4 gene. In this context, detection of the gene encoding F18 was coupled predominantly with the genes responsible for the production of the toxins ST-I, ST-II and Stx2, and the F4 gene with those of the enterotoxins ST-I, ST-II and LT. Both virulence patterns were detected more pronounced in E. coli strains with haemolytic activity. Fifty-six of a total of 83 E. coli isolates originating from calves were O-typed as O101 (O101:K28, O101:K30, O101:K32; n = 29), O78:K80 (n = 23), and O9:K35 (n = 4). Most of the E. coli O78:K80 strains carried the F17 gene (69.6%, n = 16). Virulence genes encoding for F4, F5 or ST-I were detected only in single cases. Intimin and Shiga toxin genes that are present in enterohaemorrhagic E. coli (EHEC) were not detected.


Recurrence and survival predictive value of phenotypic expression of Bcl-2 varies with tumor stage of colorectal adenocarcinoma.
Although decreased or lack of expression of Bcl-2 has been correlated with advanced tumor stage and shortened patient survival in colorectal cancer (CRC), its value in predicting the recurrence has not been well explored. Therefore, we assessed the usefulness of phenotypic expression of Bcl-2 in non-Hispanic Caucasian patients with CRCs in identifying risk of recurrence. Archival tissues of 92 Stage II and 66 Stage III primary CRCs were evaluated for immunohistochemical expression of Bcl-2. None of these patients received either pre- or post-surgical adjuvant therapies. Kaplan-Meier and Cox proportional hazards methods were used to estimate the rates of recurrence and survival according to Bcl-2 expression. Decreased expression of Bcl-2 was associated with an increased rate of recurrence in patients with Stage II CRCs (5-year log-rank test P=0.0015; Hazard Ratio (HR)=3.90, 95%C.I.:1.55-9.77) but not with Stage III CRCs (5-year log-rank test P=0.6058; HR=1.07, 95%C.I.:0.47-2.45) after adjusting for other demographic and clinicopathological features. Furthermore, decreased expression of Bcl-2 was an indicator of short survival in patients with Stage II CRCs but not with Stage III CRCs. Thus, decreased or lack of Bcl-2 expression in primary CRCs may serve as a molecular biomarker of high risk of recurrence for Caucasian patients with Stage II CRCs. These findings might be useful in identifying biologically aggressive phenotypes of Stage II CRCs, and may aid the oncologist in designing maximally appropriate therapeutic regimens.


Root Exudates of Stressed Plants Stimulate and Attract Trichoderma Soil Fungi.
Plant roots release complex mixtures of bioactive molecules, including compounds that affect the activity and modify the composition of the rhizosphere microbiome. In this work, we investigated the initial phase of the interaction between tomato and an effective biocontrol strain of Trichoderma harzianum (T22). We found that root exudates (RE), obtained from plants grown in a split-root system and exposed to various biotic and abiotic stress factors (wounding, salt, pathogen attack), were able to stimulate the growth and act as chemoattractants of the biocontrol fungus. On the other hand, some of the treatments did not result in an enhanced chemotropism on Fusarium oxysporum f. sp. lycopersici, indicating a mechanism that may be selective for nonpathogenic microbes. The involvement of peroxidases and oxylipins, both known to be released by roots in response to stress, was demonstrated by using RE fractions containing these molecules or their commercial purified analogs, testing the effect of an inhibitor, and characterizing the complex pattern of these metabolites released by tomato roots both locally and systemically.


A new recycling technique for the waste tires reuse.
In this series of laboratory experiments, the feasibility of using fixed bed biofilm carriers (FBBC) manufactured from existing reclaimed waste tires (RWTs) for wastewater treatment was evaluated. To assess polyamide yarn waste tires as a media, the fixed bed sequence batch reactor (FBSBR) was evaluated under different organic loading rate (OLRs). An experimental model was used to study the kinetics of substrate consumption in biofilm. Removal efficiency of soluble chemical oxygen demand (SCOD) ranged by 76-98% for the FBSBR compared to 71-96% in a sequencing batch reactor (SBR). Removal efficiency of FBBC was significantly increased by inoculating these RWTs carriers. The results revealed that the sludge production yield (Yobs) was significantly less in the FBSBR compared to the SBR (p < 0.01). It also produced less sludge and recorded a lower stabilization ratio (VSS/TSS). The findings show that the Stover-Kincannon model was the best fit (R2 > 99%) in a FBSBR. Results from this study suggest that RWTs to support biological activity for a variety of wastewater treatment applications as a biofilm carrier have high potential that better performance as COD and TSS removal and sludge settling properties and effluent quality supported these findings.


Low-Cost and Durable Bipolar Plates for Proton Exchange Membrane Electrolyzers.
Cost reduction and high efficiency are the mayor challenges for sustainable H2 production via proton exchange membrane (PEM) electrolysis. Titanium-based components such as bipolar plates (BPP) have the largest contribution to the capital cost. This work proposes the use of stainless steel BPPs coated with Nb and Ti by magnetron sputtering physical vapor deposition (PVD) and vacuum plasma spraying (VPS), respectively. The physical properties of the coatings are thoroughly characterized by scanning electron, atomic force microscopies (SEM, AFM); and X-ray diffraction, photoelectron spectroscopies (XRD, XPS). The Ti coating (50 μm) protects the stainless steel substrate against corrosion, while a 50-fold thinner layer of Nb decreases the contact resistance by almost one order of magnitude. The Nb/Ti-coated stainless steel bipolar BPPs endure the harsh environment of the anode for more than 1000 h of operation under nominal conditions, showing a potential use in PEM electrolyzers for large-scale H2 production from renewables.


Effects of scFOS on the composition of fecal microbiota and anxiety in patients with irritable bowel syndrome: a randomized, double blind, placebo controlled study.
Short-chain fructooligosaccharides (scFOS) have beneficial effects in subjects with minor digestive complaints, but the potential mechanisms involved have not been elucidated. The aim of the study was to evaluate changes in rectal sensitivity related to the clinical effects of scFOS in a selected group of patients with irritable bowel syndrome (IBS) and rectal hypersensitivity. In 79 IBS patients (defined by Rome III criteria) with rectal hypersensitivity (defined as discomfort threshold ≤44 g) a parallel, placebo-controlled, randomized, and double-blind study was performed to assess the effects of dietary supplementation (5 g d-1 ) with scFOS vs placebo for 4 weeks on rectal sensitivity (primary outcome: tolerance to increasing wall tension applied by a tensostat), clinical outcomes (IBS, anxiety/depression and quality of life scores) and composition of fecal microbiota. Rectal discomfort threshold, and IBS and quality of life scores, significantly improved during treatment, but in a similar manner in both scFOS and placebo groups; a post-hoc analysis showed that the effect of scFOS on rectal sensitivity was more pronounced in constipation-predominant-IBS patients (P=.051 vs placebo). Contrary with placebo, scFOS significantly reduced anxiety scores and increased fecal Bifidobacteria (P<.05 for both) without modifying other bacterial groups. The effect of scFOS on anxiety may be related to modulation of the gut microbiota; demonstration of effects of scFOS on rectal sensitivity may require higher doses and may depend on the IBS subgroup.


Assessment of parent knowledge and perception towards the importance of child immunization in Sudair region, Saudi Arabia.
According to WHO, global coverage of immunization was 86% in 2019, which dropped to 83% in 2020. The objective of this study is to assess parental knowledge and identify their perception towards the importance of child immunization. This study has also tried to determine the possible influencing factors for parental decision-making towards child immunization. A community-based cross-sectional study was conducted in 2020 in Sudair region of Saudi Arabia. The study was done among parents residing in Sudair region, where the sample was randomly selected based on the household. The sample of 436 was taken using the population proportion formula. Data were collected and analyzed using SPSS version 18 (SPSS Inc., Chicago, IL, USA). Both the descriptive and inferential statistics were used to draw the results. In this study the three-fourth (77.1%) of respondents were female and the remaining were male (23%). The majority of the respondent's knowledge was reported to have some form of influence on their idea of immunization followed by Ministry of Health, family members, medical staff, social media and others. A significant association was seen between age, marital status, occupational status and parents' knowledge on the importance of immunization (thinking if all child immunization was important). Association was also seen between parents' perception that immunization causes serious side effects and the age of the respondents. The specific programs and bcc materials are needed to enhance the knowledge and perception of individuals regarding the need for complete immunization and also regarding the fact of vaccine-preventable diseases.


All-Female Species of the Lizard Genus Cnemidophorus, Teiidae.
Six species of lizards in the genus Cnemidophorus, Teiidae, have been found to be all-female or virtually all-female. The species are C. costatus exsanguis Lowe, C. deppei cozumelus Gadow, C. inornatus Baird (western population), C. perplexus Baird and Girard, C. tessellatus (Say), and C. velox Springer. It is hypothesized that the explanation of these virtually all-female populations is genetic.


Rapid extraction of RNA and analysis of transcript levels in Chlamydomonas reinhardtii using real-time RT-PCR: Magnesium chelatase chlH, chlD and chlI gene expression.
The reverse transcriptase polymerase chain reaction (RT-PCR) is an extremely sensitive technique for detecting RNA transcripts. Real-time RT-PCR using fluorescent dyes and instruments such as the Roche Lightcycler allows real-time kinetic quantification of transcript levels. Here we report a method for the relative quantification of RNA transcripts using real-time RT-PCR that gives results comparable to Northern blotting utilizing 10-100 fold less RNA. We have also optimized a method for the rapid and efficient extraction of RNA from Chlamydomonas reinhardtii. The method is more rapid than other methods tested, allows simultaneous processing of multiple samples, and yields reproducible quantities of total RNA from a fixed number of cells. In addition the purified total RNA is of high quality and polyA-mRNA can be easily isolated. Using these methods we found that the pattern of changes in RNA transcript levels of the magnesium chelatase (Mg-chelatase) genes, chlH, chlD and chlI, of C. reinhardtii grown under synchronous culture conditions in light/dark cycles are similar and that light is involved in this regulation.


Incident reporting: clarifying occurrences, incidents, and sentinel events.
The reporting, documentation, and evaluation of incident reports must be viewed as an educational process rather than as a punitive one. This article outlines the various ways to classify incidents: as a service occurrence, a serious incident, or a sentinel event.


Taxing soft drinks and restricting access to vending machines to curb child obesity.
One of the largest drivers of the current obesity epidemic is thought to be excessive consumption of sugar-sweetened beverages. Some have proposed vending machine restrictions and taxing soft drinks to curb children's consumption of soft drinks; to a large extent, these policies have not been evaluated empirically. We examine these policies using two nationally representative data sets and find no evidence that, as currently practiced, either is effective at reducing children's weight. We conclude by outlining changes that may increase their effectiveness, such as implementing comprehensive restrictions on access to soft drinks in schools and imposing higher tax rates than are currently in place in many jurisdictions.


To strengthen and refresh: herbal therapy in Southeast Asia.
Throughout Southeast Asia herbal tonic drinks are a long established part of the health adaptation system of both rural and urban households. A recent study on infant feeding practices in urban poor households revealed a differential use of postpartum herbal tonics in Bangkok, Thailand and Semarang, Indonesia. This paper explores the cultural meaning of this difference between comparable groups of mothers, focussing on the colonial and neocolonial development of the medical systems, the transmission of knowledge about herbal therapies, and how the tonics fit into the food-drug classification system in both countries.


The window for embryo transfer in oocyte donation cycles depends on the duration of progesterone therapy.
In 192 oocyte donation cycles performed between January 1993 and July 1996, we examined the width of 'the window for embryo transfer' using standard hormonal replacement methods. All transfers were performed within 48 h of insemination. We varied the day of embryo transfer with regard to the initiation of progesterone therapy and, thus, the duration of endometrial exposure to progesterone and analysed the resulting pregnancy rates. Patients were divided into five groups (I-V) and embryo transfers were performed 2, 3, 4, 5 or 6 days following initiation of progesterone therapy. The number of pregnancies per transfer cycle achieved in groups I-V were 0 (0%), 3 (12%), 16 (40%), 29 (48.3%), and 10 (20.4%) respectively. The increased pregnancy rate in group III in comparison to group II is statistically significant (P < 0.03). Furthermore, the pregnancy rate in group IV (5 days of progesterone administration before embryo transfer) was significantly higher than in group V (6 days of progesterone administration before embryo transfer; P < 0.005). We also noted that, when embryos were transferred 4 or 5 days after initiation of progesterone therapy, the pregnancy rates were not significantly different between menopausal and cycling recipients (50% vs 43.7%). Our results indicate that the window for embryo transfer is dependent on duration of treatment with progesterone; it begins approximately 48 h after starting progesterone administration and lasts for approximately 4 days. The optimum period for transferring embryos at the 4- to 8-cell stage corresponds to cycle days 18 and 19. Transfers performed on the 17th and 20th days of the cycle can result in successful implantation, although the rates of implantation are highest when transfers are done on days 18 and 19.


Investigation of serum isthmin 1 concentration in pregnant women diagnosed with gestational diabetes mellitus; a case-control study.
Isthmin 1 (ISM1) is an adipokine that improves hyperglycemia by increasing glucose uptake in a non-insulin-dependent manner. Studies have shown that ISM is associated with the development of type 2 diabetes mellitus. Based on this, we aimed to investigate serum ISM1 concentrations of pregnant women with gestational diabetes mellitus (GDM). This case-control study was conducted with 80 pregnant women who applied to the Gynecology and Obstetrics Clinic of Umraniye Training and Research Hospital between April 2022 and November 2022. While 40 pregnant women diagnosed with GDM according to 75 g OGTT results formed the GDM group, 40 pregnant women with normal OGTT results formed the control group. The two groups were compared in terms of serum ISM1 concentrations. Both groups were similar in terms of demographic characteristics (p > 0.05). Fasting blood glucose levels, 1st-hour and 2nd-hour blood glucose levels in 75 g OGTT, fasting insulin levels, and HOMA-IR were significantly higher in the GDM group (p > 0.05, for each). Both groups were similar in terms of maternal waist circumference, periumbilical, and epigastric subcutaneous adipose tissue thickness (p > 0.05, for each).Both groups were similar in terms of the gestational week at blood sampling for ISM1 (p = 0.253). The median maternal serum ISM1 concentration was found to be 3243.94 pg/ml in the GDM group, while it was determined as 2785.29 pg/ml in the non-GDM group (p = 0.026).ROC analysis was performed to determine the value of maternal serum ISM1 concentration in predicting GDM. AUC analysis of maternal serum ISM1 for estimation of GDM was 0.645 (p = 0.026, 95% CI = 0.523 - 0.766). The optimal threshold value for maternal serum ISM1 concentration was determined as 3124.41 pg/ml with 62.5% sensitivity and 62.5% specificity. Serum ISM1 concentrations were found to be higher in pregnant women with GDM than in healthy controls. Whether or how ISM1 participates in the pathophysiology of GDM remains to be investigated.


Estimating the costs of medicalization.
Medicalization is the process by which non-medical problems become defined and treated as medical problems, usually as illnesses or disorders. There has been growing concern with the possibility that medicalization is driving increased health care costs. In this paper we estimate the medical spending in the U.S. of identified medicalized conditions at approximately $77 billion in 2005, 3.9% of total domestic expenditures on health care. This estimate is based on the direct costs associated with twelve medicalized conditions. Although due to data limitations this estimate does not include all medicalized conditions, it can inform future debates about health care spending and medicalization.


Acute kidney injury: an unusual complication of posaconazole use.
Triazole antifungals are useful in the treatment of Aspergillus disease and these drugs have side effects which clinicians should be aware of. Posaconazole is an orally administered second-generation triazole antifungal agent which inhibits lanosterol 14-alpha-demethylase, an enzyme that converts lanosterol to ergosterol, a vital component of the fungal cell membrane. Posaconazole has a favorable side effect profile, is safe and well tolerated when compared to the earlier generation of triazole antifungals. Common side effects of posaconazole include gastrointestinal, hepatobiliary, neurological, and skin and subcutaneous disorders. Renal disorders are classed as an uncommon side effect of posaconazole, occurring in ∼0.1-1% of patients. We describe 2 episodes of acute kidney injury (AKI) in a Caucasian whose Aspergillus lung disease was being treated with posaconazole. Regular monitoring of renal function may be necessary for patients on posaconazole to facilitate early identification of acute kidney injury which is reversible.


Induction of tumor-specific cytotoxic T lymphocytes by immunization with autologous tumor cells and interleukin-2 gene transfected fibroblasts.
In a phase I trial designed to study a vaccine composed of autologous tumor cells and interleukin-2 gene transfected fibroblasts we analyzed lymphocytes infiltrating the vaccination site (VIL) in two melanoma patients. Functional studies demonstrated that numbers of MHC class I restricted cytotoxic T cells directed against the autologous tumor had increased at the immunization site in both cases. Analysis of the variability of T cell receptors (TCR) in the VIL of one patient revealed that the cytotoxic T lymphocytes consisted of a predominant population of TCRBV21S3+ T cells. Enrichment of this subpopulation to more than 99% by specific anti-TCRBV21S3 monoclonal antibody linked immunomagnetic beads and sequencing of the TCR-beta chain disclosed exactly the same V-D-J junctional sequence in all eight TCRBV21 transcripts from these VIL. The identical sequence was also detected in all eight TCRBV21 transcripts from the patient's tumor-infiltrating lymphocytes, indicating that the same CTL clone had infiltrated the tumor, circulated in the peripheral blood, and was amplified at the vaccination site. The TCRBV21S3+ T cells were also found to display an MHC class I restricted cytotoxic activity specifically directed against the autologous tumor cells. At the beginning of treatment these cells were undetectable at the vaccination site and delayed-type hypersensitivity testing was negative, contrasting with the positive results after therapy. Thus it is likely that vaccination with autologous tumor cells plus interleukin-2 gene transfected allogeneic fibroblasts had induced not only local accumulation but also an increase in the frequency of circulating tumor specific CTL.


Discourse ethics: research, dementia, and communication.
This article begins with a brief statement of why Alzheimer disease (AD) research is an especially significant issue in bioethics. It then describes "discourse ethics" as an ethical methodology well suited for public deliberation on this topic. Finally, the article takes up the practical importance of communication techniques in research with AD-affected people, a point of emphasis that naturally arises from the idea of discourse ethics.


Proarrhythmic potential of moricizine: strengths and limitations of a data base analysis.
Moricizine was studied in 908 patients with ventricular arrhythmias. A proarrhythmia occurred in 29 (3.2%). When the severity of the proarrhythmia and the type of presenting ventricular arrhythmia were correlated, no proarrhythmic events occurred in patients who presented with benign ventricular arrhythmias. Four deaths were attributed to the proarrhythmic effects of moricizine. Of these, 3 occurred in patients presenting with lethal ventricular arrhythmias. A total of 15 serious proarrhythmic events occurred, all of which resolved without lethal consequence. The overall proarrhythmia incidence in the lethal and potentially lethal ventricular arrhythmia categories was not different (3.2 vs 3.7%, respectively). Thus, a proarrhythmia occurred in patients with more advanced structural heart disease, and occurred almost exclusively in patients who presented with potentially lethal or lethal ventricular arrhythmia. There was no relation between the dose of moricizine and the incidence of proarrhythmic events. Of the 29 proarrhythmic events, 26 occurred within 7 days (90%) of the initiation of moricizine therapy. Thus, moricizine appears to have a low proarrhythmic potential in the populations tested, including patients presenting with lethal ventricular arrhythmias. The implications of the Cardiac Arrhythmia Suppression Trial on such a data base analysis are discussed.


Salvage of major amputation stumps of the lower extremity with latissimus dorsi free flaps.
In some severe lower limb injuries, the level of bone trauma enables preservation of the knee joint or adequate length of the femoral stump only if the soft tissues can be reconstructed over the exposed bone. The options for soft-tissue reconstruction of an amputation stump are to use a flap from the amputated distal part, a local flap possibly after tissue expansion or a free flap. To preserve an adequate length of stump we reconstructed 10 stumps with latissimus dorsi free flaps: above the knee in one patient and below the knee in nine. The reconstructions were done during an acute post-traumatic phase in five and for late problems with the stump in four patients. In one patient the reconstruction was done nine weeks after a below-knee amputation for ischaemic necrosis after septicaemia. All flaps survived, but the venous anastomosis had to be revised in three patients in the early postoperative period. All patients regained adequate ambulation for their daily activities. The flap was secondarily debulked in three patients. Every effort should be made to preserve an adequate stump length, particularly in young patients with crushing injuries of the extremities and when there is severe or recurrent late stump ulceration. A latissimus dorsi musculocutaneous soft-tissue reconstruction is a reliable and durable option for stump defects.


Purification and characterization of guinea pig gastric phospholipase A2 of the pancreatic type.
Guinea pig gastric mucosa and juice contained exceptionally high phospholipase-A2 activity, whereas the activity in the pancreas was only minimal. Phospholipases A2 were purified to homogeneity from these three tissues. Structural evidence, including the sequence of the NH2-terminal 41 residues, the amino-acid composition and the molecular mass (13902 +/- 3 Da) determined accurately by mass spectrometry, showed that the gastric mucosa enzyme belongs to the pancreatic type. An unique feature of the sequence is the substitution of Phe for the hitherto invariant Tyr28 in the calcium-binding loop of pancreatic phospholipases A2. The affinity of the guinea pig enzyme for Ca2+ in the presence of substrate was, however, identical to that of the rat enzyme with Tyr28, suggesting the interaction of a phenolic hydroxyl group of the Tyr with its neighboring residues is not significantly linked to the binding of Ca2+. The NH2-terminal sequences and immunochemical properties of the enzymes purified from the gastric juice and pancreas were identical to those of the gastric mucosa enzyme. The distribution of cells immunoreactive with anti-(gastric PLA2) immunoglobulin in the stomach was quite similar to that of the chief cells. Unlike in pancreas of other animals, the prophospholipase A2 was not detectable in gastric mucosa or juice homogenates treated with diisopropyl fluorophosphate or in column effluents during purification under acidic conditions. An appreciable prophospholipase-A2-activating activity was not detectable in gastric mucosa extracts at low pH relevant to gastric juice, using rat prophospholipase A2 as substrate. This opposes the activation of secreted proenzyme in the gastric juice.


Association between Optimism, Psychosocial Well Being and Oral Health: A Cross-Sectional Study.
The aim of the study was to assess the association of optimism and psychosocial well being of school going children on their oral health status. The study included 12- to 15-year-old school going children (N = 2014) from Tamilnadu, India. Optimism was measured using the revised version of the Life Orientation Test (LOT-R). A questionnaire was sent to the parents regarding their child's psychosocial behavior which included shyness, feeling inferiority, unhappiness and friendliness. Clinical examination for each child was done to assess the DMFT score and OHI-S score. The data obtained were statistically analyzed using Pearson Chi-Square test, Mann-Whitney test and Kruskal-Wallis test with the aid of SPSS software (version 17). Odds Ratio (OR) was calculated with 95% Confidence Interval (CI). The p value ≤ 0.05 was considered statistically significant. Boys with high optimism had significantly lesser DMFT score than the boys with low optimism (p=0.001). Girls with high optimism had significantly higher DMFT score (p=0.001). In psychosocial outcomes, inferiority (p=0.002) and friendliness (p=0.001) showed significant association with DMFT score. Among the boys, children who felt less inferior (p=0.001), less unhappy (p=0.029) and more friendly (p=0.001) had lesser DMFT score. Among the psychosocial outcomes assessed, inferiority and friendliness had significant association with oral health of the children and hence, can be used as a proxy measures oral health.


Long term increases in coronary arterial conductance during five day infusion of low dose nicorandil.
The aim was to test the effects of nicorandil on coronary arterial conductance and on a possible development of tolerance or cross tolerance with glyceryl trinitrate during a 5 d continuous intravenous infusion of this hybrid molecule (consisting of a combination of potassium channel activation and simultaneous nitro-ester induced soluble guanylyl-cyclase activation). Continuous intravenous infusions of nicorandil at 2.5 micrograms.kg-1.min-1 and 10 micrograms.kg-1.min-1 into conscious chronically instrumented dogs were carried out for 5 d using a special portable infusion system. Employing additional short term infusions, dose-response curves were obtained by giving nicorandil or glyceryl trinitrate at increasing dosages both in the preinfusion control state and 4 h after terminating the nicorandil infusion. The 5 d infusion of 2.5 or 10.0 micrograms.kg-1.min-1 nicorandil resulted in a significant increase in large coronary artery diameter by 4.21 (SEM 0.14)% or 9.20(0.28)%, respectively. At the lower dose no significant tolerance or cross tolerance with glyceryl trinitrate was observed. However, at the higher dose there was a shift of the dose-response curve of both nicorandil and glyceryl trinitrate to the right, indicating some tolerance. The smaller dose did not induce hypotension or reflex increase in heart rate, whereas the larger resulted in a 42(2.5)% increase in heart rate. A dose regimen of 2.5 micrograms.kg-1.min-1 continuously administered for 5 d is capable of inducing a significant increase in coronary arterial conductance which was well maintained over the whole infusion period. Thus nicorandil can exert a selective large coronary artery dilatation and may bring about a well maintained increase in epicardial coronary conductance, especially when applied as a low dose slow release preparation which circumvents hypotension and increase in heart rate.


Demonstration of Model-Independent Control of the Longitudinal Phase Space of Electron Beams in the Linac-Coherent Light Source with Femtosecond Resolution.
The dynamics of intense electron bunches in free electron lasers and plasma wakefield accelerators are dominated by complex collective effects such as wakefields, space charge, coherent synchrotron radiation, and drift unpredictably with time, making it difficult to control and tune beam properties using model-based approaches. We report on a first of its kind combination of automatic, model-independent feedback with a neural network for control of the longitudinal phase space of relativistic electron beams with femtosecond resolution based only on transverse deflecting cavity measurements.


Tilted versus axial implant distribution in the posterior edentulous maxilla: A CBCT analysis.
This study aimed to determine whether distally angulating an implant is a successful strategy to avoid the maxillary sinus and the need for bone augmentation, while increasing the anterior-posterior (A-P) implant distribution in the edentulous maxilla. In 115 patients with edentulous maxillae, virtual implant planning was performed utilizing cone-beam computer tomographs. Axial (8 mm length) and tilted (12 mm length) dental implants with 30-degree and 45-degree angulation were virtually positioned to avoid entering the maxillary sinus, while maximizing A-P distribution. Measurements were made between the tilted and axial implants to assess the change in A-P distribution of implants at the implant and abutment levels. Forty-seven sites (20.4%) were not able to have either treatment modality with insufficient bone for implant placement. Axial implants were placed more distally than 45-degree and 30-degree tilted implants in 24% and 42% of sites, respectively. The average change in A-P spread measured at the implant level, for 30- and 45-degree tilted implants was -0.25 mm (95% CI -0.76, 0.26) and 1.9 mm (95% CI 1.4, 2.3), respectively. When measured from the center of each multi-unit abutment the average increase in A-P distances for tilted implants appears larger in the 30-degree and 45-degree groups by 0.97 mm and 1.74 mm, respectively compared to measurements at the implant level. Angulating 12 mm implants provides a limited increase in A-P distribution of implants in edentulous rehabilitation in most situations. In certain patients, the use of 8mm axial implants may provide a greater A-P spread.


Precise and Efficient Pointing Control of a 2.5-m-Wide Field Survey Telescope Using ADRC and Nonlinear Disturbance Observer.
Linear active disturbance rejection control (LADRC) has been widely used to improve the tracking accuracy and anti-disturbance performance of telescope servo control under disturbances. However, the linear extended state observer (LESO) is sensitive to noise, and its bandwidth is limited by the resonant frequency of the telescope. To enhance the LARDC's ability to attenuate disturbances, a novel cascade anti-disturbance structure (NCADS) with LADRC on the outer speed loop and a nonlinear disturbance observer (NDOB) on the inner current loop is proposed. The NDOB compensates for the dominant disturbance through feedforwarding the q-axis current reference, and the LESO compensates for the residual disturbance on the outer speed loop. First, the NCADS is introduced in a three-closed-loop control framework of PMSM. Then, the design method of the controller for each loop and the NDOB are presented, the parameter-tuning method based on bandwidth is demonstrated, and the convergence of the NDOB is proved. Furthermore, to improve the searching and tracking efficiency of wide-field survey telescopes, the nonlinear tracking differentiator (NTD) was modified to plan the transition process of the position loop, which only needs to set the maximum speed and acceleration of the telescope. Finally, simulations and experiments were performed on a 2.5-m-wide field survey telescope. The experimental results verify that the proposed NCADS method has a better anti-disturbance performance and higher tracking precision than the conventional method, and the improved NTD method does not need to tune parameters and achieved a fast and smooth transition process of the position loop.


Comparative geno-plasticity analysis of Mycoplasma bovis HB0801 (Chinese isolate).
Mycoplasma bovis pneumonia in cattle has been epidemic in China since 2008. To investigate M. bovis pathogenesis, we completed genome sequencing of strain HB0801 isolated from a lesioned bovine lung from Hubei, China. The genomic plasticity was determined by comparing HB0801 with M. bovis strain ATCC® 25523™/PG45 from cow mastitis milk, Chinese strain Hubei-1 from lesioned lung tissue, and 16 other Mycoplasmas species. Compared to PG45, the genome size of HB0801 was reduced by 11.7 kb. Furthermore, a large chromosome inversion (580 kb) was confirmed in all Chinese isolates including HB0801, HB1007, a strain from cow mastitis milk, and Hubei-1. In addition, the variable surface lipoproteins (vsp) gene cluster existed in HB0801, but contained less than half of the genes, and had poor identity to that in PG45, but they had conserved structures. Further inter-strain comparisons revealed other mechanisms of gene acquisition and loss in HB0801 that primarily involved insertion sequence (IS) elements, integrative conjugative element, restriction and modification systems, and some lipoproteins and transmembrane proteins. Subsequently, PG45 and HB0801 virulence in cattle was compared. Results indicated that both strains were pathogenic to cattle. The scores of gross pathological assessment for the control group, and the PG45- and HB0801-infected groups were 3, 13 and 9, respectively. Meanwhile the scores of lung lesion for these three groups were 36, 70, and 69, respectively. In addition, immunohistochemistry detection demonstrated that both strains were similarly distributed in lungs and lymph nodes. Although PG45 showed slightly higher virulence in calves than HB0801, there was no statistical difference between the strains (P>0.05). Compared to Hubei-1, a total of 122 SNP loci were disclosed in HB0801. In conclusion, although genomic plasticity was thought to be an evolutionary advantage, it did not apparently affect virulence of M. bovis strains in cattle.