Role of parathyroid hormone therapy in reversing radiation-induced nonunion and normalization of radiomorphometrics in a murine mandibular model of distraction osteogenesis.
The use of mandibular distraction osteogenesis (MDO) for tissue replacement after oncologic resection or for defects caused by osteoradionecrosis has been described but, in fact, has seen limited clinical utility. Previous laboratory work has shown that radiation (XRT) causes decreased union formation, decreased cellularity, and decreased mineral density in an animal model of MDO. Our global hypothesis is that radiation-induced bone damage is partly driven by the pathologic depletion of both the number and function of osteogenic cells. Parathyroid hormone (PTH) is a U.S. Food and Drug Administration-approved anabolic hormonal therapy that has demonstrated efficacy for increasing bone mineral density for the treatment of osteoporosis. We postulate that intermittent systemic administration of PTH will serve as an anabolic stimulant to cellular function that will act to reverse radiation-induced damage and enhance bone regeneration in a murine mandibular model of DO. A total of 20 isogenic male Lewis rats were randomly assigned into 3 groups. Group 1 (XRT-DO, n = 7) and group 2 (XRT-DO-PTH, n = 5) received a human bioequivalent dose of 70 Gy fractionated over 5 days. All groups including group 3 (DO, n = 8) underwent a left unilateral mandibular osteotomy with bilateral external fixator placement. Four days later, mandibular DO was performed at a rate of 0.3 mm every 12 hours to reach a maximum gap of 5.1 mm. Group 2 was injected PTH (60 μg/kg) subcutaneously daily for 3 weeks following the start of MDO. On postoperative day 41, all left hemimandibles were harvested. Micro-CT at 45-μm voxel size was performed and radiomorphometrics parameters of bone mineralization were generated. Union quality was evaluated on a 4-point qualitative grading scale. Radiomorphometric data were analyzed using 1-way ANOVA, and union quality assessment was analyzed via the Mann-Whitney test. Statistical significance was considered at p ≤ .05. Groups 1 and 2 appropriately demonstrated clinical signs of radiation-induced stress ranging from alopecia to mucositis. Union quality was significantly higher in PTH-treated XRT-DO animals, compared with XRT-DO group animals (p = .02). Mineralization metrics, including bone volume fraction (BVF) and bone mineral density (BMD), also showed statistically significant improvement. The groups that were treated with PTH showed no statistical differences in union or radiomorphometrics when compared with DO in nonradiated animals. We have successfully demonstrated the therapeutic efficacy of PTH to stimulate and enhance bone regeneration in our irradiated murine mandibular model of DO. Our investigation effectively resulted in statistically significant increases in BMD, BVF, and clinical unions in PTH-treated mandibles. PTH demonstrates immense potential to treat clinical pathologies where remediation of bone regeneration is essential.


Coding of information about tactile stimuli by neurones of the cuneate nucleus.
1. The responses of cuneate neurones to controlled tactile stimulation of the foot pads were examined in unanaesthetized, decerebrate cats. The neurones were divided into three functional classes; one sensitive to steady tactile stimuli, and two dynamically sensitive classes which could be readily differentiated by their responsiveness to cutaneous vibration. Each class appeared to receive an exclusive input from only one of the three known groups of tactile receptors associated with the foot pads, namely the Pacinian corpuscles, the Merkel endings and the intradermal, encapsulated endings known as Krause or Meissner corpuscles. 2. Cuneate neurones responsive to steady indentation of the skin displayed approximately linear or sigmoidal stimulus-response relations over indentation ranges up to approximately 1.5--2 mm. Response variability at a fixed stimulus intensity was relatively low and showed little systematic change over the full range of the stimulus-response curves. 3. One class of dynamically sensitive cuneate neurones responded to cutaneous vibration over a range of approximately 5-80 Hz with maximal responsiveness around 30 Hz. The other class, the Pacinian neurones, responded over a range of approximately 80- greater than 600 Hz with maximal responsiveness at 200-400 Hz. The thresholds and combined band width of vibratory sensitivity of these populations were comparable with known subjective thresholds and range of cutaneous vibratory sensibility. 4. Responses of cuneate neurones were phase-locked to the vibratory stimulus suggesting that information about vibration frequency could be coded by the patterns of impulse activity. Quantitative measures indicated that maximal phase-locking occurred in responses to vibration frequencies of 10-50 Hz with a progressive decline at higher frequencies. Above 400 Hz, impulse activity occurred almost randomly throughout the vibratory stimulus cycle and therefore carried little further signal of vibratory frequency. The decline, with increasing frequency, in the ability of cuneate neurones to signal information about vibratory frequency parallels the known subjective capacities for frequency discrimination. 5. A switch-over occurred at approximately 80 Hz in the population of cuneate neurones able to provide the more reliable signal of vibratory frequency; above 80 Hz, the Pacinian neurones; below 80 Hz, the neurones receiving intradermal, rapidly adapting receptor input from the pads. 6. The observed properties of cuneate neurones are compatible with a role in signalling information which could contribute to subjective tactile abilities.


Lower blepharoplasty: partially joined skin and muscle flaps.
As a method of performing a lower blepharoplasty, the author proposes a partially joined skin and muscle flap. This procedure allows one to resect separately different amounts of skin and muscle for appropriate correction of the lower-lid changes that require an aesthetic blepharoplasty. It also promotes muscle raising with consequent skin flap lifting. This technique resects a large amount of skin in order to achieve a smoother lower eyelid.


Alumina cream-induced focal motor seizures in cats. V. Unilateral lesions of the brain-stem reticular formation.
The effect of unilateral mesencephalic (MRF) and pontine (PRF) lesions on EEG-EMG patterns of type B and C alumina cream induced focal motor seizures was studied on cats with chronically implanted electrode and cannula lesion systems. EEG patterns included number, amplitude and contralateral propagation of type B spikes and occurrence and duration of type C tonic-clonic discharges. EMG patterns included changes in muscular multiple unit activity (EMG-MUA) time locked to the onset of type B spikes and to the onset (tonic OTCD) and the end (clonic ETCD) of type C tonic-clonic EEG paroxysmal discharges. (1) MRF lesions ipsilateral to the cortical epileptogenic focus significantly increased number, amplitude and propagation of type B EEG spikes and the occurrence, but not the duration, of type C EEG tonic-clonic discharges. They also reduced amplitude of type B muscular jerks and blocked type C tonic contradversion with a significant decrease in EMG-MUA time locked to the onset of type B spikes and type C paroxysmal EEG discharges. (2) PRF lesions contralateral to the cortical epileptogenic focus produced an effect on muscular contractions of type B and C seizures similar to that produced by ipsilateral MRF lesions. PRF lesions, however, did not significantly change the EEG patterns of type B and C seizures. (3) Neither MRF lesions contralateral nor PRF lesions ipsilateral to the cortical epileptogenic focus produced significant changes on EEG and EMG patterns of types B and C epileptic seizures.


[Experimental investigations concerning a topical application of sisomicin in the eye (author's transl)].
Sisomicin is a new aminoglycoside, which sometimes is active against bacterial isolates resistant to other antibiotics of this group. The compatibility of sisomicin and its penetration into the different tissues of the eye were studied in rabbits. The substance was well tolerated, when applied as drops or injected subconjunctivally. Concentrations of sisomicin which are effective against most bacteria were found in the cornea and in the aqueous humour, but it did not penetrate into the vitreous body.


Assessing extra-prostatic extension for surgical guidance in prostate cancer: Comparing two PSMA-PET tracers with the standard-of-care.
Incontinence and impotence occur following radical prostatectomy due to injury to nerves and sphincter muscle. Preserving nerves and muscle adjacent to prostate cancer risks positive surgical margins. Advanced imaging with MRI has improved cancer localization but limitations exist. To measure the accuracy for assessing extra-prostatic extension at nerve bundles for 2 PSMA-PET tracers and to compare the PET accuracy to standard-of-care predictors including MRI and biopsy results. We studied men with PSMA-targeted PET imaging, performed prior to prostatectomy in men largely with intermediate to high-risk prostate cancer, and retrospectively evaluated for assessment of extra-prostatic extension with whole-mount analysis as reference standard. Two different PSMA-PET tracers were included: 68Ga-PSMA-11 and 68Ga-P16-093. Blinded reviews of the PET and MRI scans were performed to assess extra-prostatic extension (EPE). Sensitivity and specificity for extra-prostatic extension were compared using McNemar's Chi2. Pre-operative PSMA-PET imaging was available for 71 patients with either 68Ga-P16-093 (n = 25) or 68Ga-PSMA-11 (n = 46). There were 24 (34%) with pT3a (EPE) and 16 (23%) with pT3b (SVI). EPE Sensitivity (87% vs. 92%), Specificity (77% vs. 76%), and ROC area (0.82 vs. 0.84) were similar between P16-093 and PSMA-11, respectively (P = 0.87). MRI (available in only 45) found high specificity (83%) but low sensitivity (60%) for EPE when using a published grading system. MRI sensitivity was significantly lower than the PSMA-PET (60% vs. 90%, P = 0.02), but similar to PET when using a >5 mm capsular contact (76% vs. 90%, P = 0.38). A treatment change to "nerve sparing" was recommended in 21 of 71 (30%) patients based on PSMA-PET imaging. Presurgical PSMA-PET appeared useful as a tool for surgical planning, changing treatment plans in men with ≥4+3 or multi-core 3+4 prostate cancer resulting in preservation of nerve-bundles.


Prediction of 12-Week Remission by Psychopharmacological Treatment Step in Patients With Depressive Disorders.
To investigate the predictors of remission by 4 treatment steps in depressive outpatients receiving 12-week psychopharmacotherapy. Patients were consecutively recruited at a university hospital in South Korea from March 2012 to April 2017. At baseline, 1,262 patients were evaluated for sociodemographic and clinical data including assessments scales, and were received antidepressant monotherapy. For patients with an insufficient response or uncomfortable side effects, next treatment steps (1, 2, 3, and 4) with alternative strategies (switching, augmentation, combination, and mixtures of these approaches) were administered considering measurements and patient preference at every 3 weeks in the acute treatment phase (3, 6, 9, and 12 weeks). Remission was defined as a Hamilton Depression Rating Scale score of ≤7. In the multi-variate logistic regression analyses, remission was predicted by higher functional levels in patients received Step 1 and 2 treatment; by lower life stressors in Step 1; by higher social support in Step 3 and 4; and by lower suicidality in Step 1-3. Differential associations were found between symptoms or functions and treatment steps, which suggested that multi-faceted evaluations at baseline could predict remission by treatment steps.


The effect of ET1-CTGF mediated pathway on the accumulation of extracellular matrix in the trabecular meshwork and its contribution to the increase in IOP.
To investigate the effect of endothelin-1 (ET-1) in excessive accumulation of extracellular matrix (ECM) of the trabecular meshwork (TM) and its role in intraocular pressure (IOP) regulation. Cultured human TM cells (HTMCs) were treated with ET-1, ET-1 + ETA receptor (ETAR) antagonist BQ123, ET-1 + ETB receptor (ETBR) antagonist BQ788. The expressions of fibronectin (FN) and collagen type IV (Col IV) were evaluated by western blotting and immunofluorescence. A time course effect of ET-1 on the transcription level of connective tissue growth factor (CTGF) was investigated by qRT-PCR. Next, the transcription level of CTGF was downregulated by using antisense oligodeoxynucleotide sequence. Then HTMCs were treated with ET-1, and the expression levels of FN and Col IV were evaluated by western blotting. In addition, by using an ex-vivo model of cultured anterior eye segment, we explored the effect of ET-1 on IOP changes and the expressions of FN and Col IV. In cultured HTMCs, the expressions of FN and Col IV were significantly increased after ET-1 treatment, which were blocked by the pretreatment of ETAR antagonist BQ123, rather than ETBR antagonist BQ788. Besides, the CTGF mRNA level increased significantly and reached a peak after 48 h of ET-1 treatment. However, the effect of ET-1 on increasing the expressions of FN and Col IV in HTMCs could be inhibited by the downregulation of CTGF. In an ex-vivo model, IOP increased significantly after ET-1 administration, which could be blocked by BQ123 but not by BQ788. Furthermore, elevated expressions of FN and Col IV in TM were observed after ET-1 perfusion, and could be inhibited by BQ123 pretreatment. Excessive ET-1 in aqueous humor could lead to the abnormal accumulation of FN and Col IV in TM via the ETA-CTGF pathway, thereby increasing IOP.


Atrial and brain natriuretic peptide changes in an experimental model of intra-abdominal hypertension.
Intra-abdominal hypertension (IAH) can have a profound impact on the cardiovascular system. We hypothesized that natriuretic peptides (Nt-pro-ANP and Nt-pro-BNP) are produced in response to the cardiovascular changes observed in an experimental model of IAH. Eleven female pigs were enrolled in this study. Four experimental phases were created: a baseline phase for instrumentation (T1); two subsequent phases (T2 and T3), in which helium pneumoperitoneum was established at 20 and 35 mm Hg, respectively; and the final phase (T4), in which abdominal desufflation took place. Hemodynamic parameters and concentrations of Nt-pro-ANP and Nt-pro-BNP were measured. Central venous pressure and pulmonary capillary wedge pressure increased significantly during the elevation of intra-abdominal pressure (IAP) and returned to baseline after abdominal desufflation. Right and left transmural pressures remained unaffected by the elevation of IAP. Cardiac output decreased in phases T2 and T3 and was restored to baseline levels after abdominal desufflation. Systemic and pulmonary vascular resistances increased significantly with IAH and decreased after abdominal desufflation. Nt-pro-ANP did not change significantly in comparison to baseline. Nt-pro-BNP increased significantly in comparison to baseline at T3 and T4. Peak Nt-pro-BNP levels at T3 (peak IAP) correlated positively with indices of afterload at this time point, that is, systemic vascular resistance and pulmonary vascular resistance (r(2) = 0.38, P = 0.042 and r(2) = 0.55, P = 0.009, respectively). A strong negative correlation between Nt-pro-BNP and cardiac output at T3 was also demonstrated (r(2) = 0.58, P = 0.006). IAH resulted in cardiovascular compromise. The unchanged Nt-pro-ANP concentrations might reflect unaltered atrial stretch with IAH, despite the elevation of right atrial filling pressure. The significant increase of Nt-pro-BNP in response to high levels of IAP may reflect left ventricular strain and dysfunction due to the severe IAH and provide an alternative marker in the monitoring of IAH.


MutY catalytic core, mutant and bound adenine structures define specificity for DNA repair enzyme superfamily.
The DNA glycosylase MutY, which is a member of the Helix-hairpin-Helix (HhH) DNA glycosylase superfamily, excises adenine from mispairs with 8-oxoguanine and guanine. High-resolution crystal structures of the MutY catalytic core (cMutY), the complex with bound adenine, and designed mutants reveal the basis for adenine specificity and glycosyl bond cleavage chemistry. The two cMutY helical domains form a positively-charged groove with the adenine-specific pocket at their interface. The Watson-Crick hydrogen bond partners of the bound adenine are substituted by protein atoms, confirming a nucleotide flipping mechanism, and supporting a specific DNA binding orientation by MutY and structurally related DNA glycosylases.


Social isolation, loneliness and physical performance in older-adults: fixed effects analyses of a cohort study.
Isolation and loneliness are related to various aspects of health. Physical performance is a central component of health. However, its relationship with isolation and loneliness is not well understood. We therefore assessed the relationship between loneliness, different aspects of social isolation, and physical performance over time. 8,780 participants from the English Longitudinal Study of Ageing, assessed three times over 8 years of follow-up, were included. Measures included physical performance (Short Physical Performance Battery), loneliness (modified UCLA Loneliness Scale), and isolation considered in three ways (domestic isolation, social disengagement, low social contact). Fixed effects regression models were used to estimate the relationship between changes in these parameters. Missing data were imputed to account for variable response and ensure a representative sample. Loneliness, domestic isolation and social disengagement were longitudinally associated with poorer physical performance when accounting for both time-invariant and time-variant confounders (loneliness: coef = - 0.06, 95% CI - 0.09 to - 0.02; domestic isolation: coef = - 0.32, 95% CI - 0.46 to - 0.19; social disengagement: coef = - 0.10, 95% CI - 0.12 to - 0.07). Low social contact was not associated with physical performance. These findings suggest social participation and subjectively meaningful interpersonal interactions are related to physical performance, and highlight additional considerations regarding social distancing related to COVID-19 control measures.


Triggered release of model drug from AuNP-doped BSA nanocarriers in hair follicles using IRA radiation.
Recent advances in the field of dermatotherapy have resulted in research efforts focusing on the use of particle-based drug delivery systems for the stimuli-responsive release of drugs in the skin and skin appendages, i.e. hair follicles and sebaceous glands. However, effective and innocuous trigger mechanisms which result in the release of the drugs from the nanocarriers upon reaching the target structures are still lacking. For the first time, the present study demonstrated the photo-activated release of the model drug fluorescein isothiocyanate (FITC) from topically applied gold nanoparticle-doped bovine serum albumin (AuNPs-doped BSA) particles (approx. 545nm) using water-filtered infrared A (IRA) radiation in the hair follicles of an ex vivo porcine skin model. The IRA radiation-induced plasmonic heating of the AuNPs results in the partial decomposition or opening of the albumin particles and release the model drug, while control particles without AuNPs show insignificant release. The results demonstrate the feasibility of using IRA radiation to induce release of encapsulated drugs from plasmonic nanocarriers for the targeting of follicular structures. However, the risk of radiation-induced skin damage subsequent to repeated applications of high infrared dosages may be significant. Future studies should aim at determining the suitability of lower infrared A dosages, such as for medical treatment regimens which may necessitate repeated exposure to therapeutics. Follicular targeting using nanocarriers is of increasing importance in the prophylaxis and treatment of dermatological or other diseases. For the first time, the present study demonstrated the photo-activated release of the model drug fluorescein isothiocyanate (FITC) from topically applied gold nanoparticle-doped bovine serum albumin (AuNPs-doped BSA) particles using water-filtered infrared A (IRA) radiation in the hair follicles of an ex vivo porcine skin model. The results demonstrate the feasibility of using wIRA radiation to induce release of encapsulated drugs for the targeting of follicular structures, and provide a new vision on the development of optically addressable delivery systems for controlled release of drugs in the skin and skin appendages, i.e. hair follicles and sebaceous glands.


Placental protein 10 (PP10) in singleton and twin pregnancy complicated by pre-eclampsia.
Circulating levels of placental protein 10 (PP10) were measured by radioimmunoassay in 140 women with normal singleton pregnancy (140 samples), in 6 women with normal twin pregnancy (15 samples) and in 35 pregnant women with pre-eclampsia (51 samples from singleton pregnancies and 7 samples from twin pregnancies) between 24 and 40 weeks. In singleton pregnancies with pre-eclampsia, the levels were lower than normal (P less than 0.01). In twin pregnancy the circulating PP10 levels were not significantly affected. These results suggest that changes in placental function are reflected in the circulating PP10 levels.


Multidrug-loaded electrospun micro/nanofibrous membranes: Fabrication strategies, release behaviors and applications in regenerative medicine.
Electrospun micro/nanofibrous membranes (EFMs) have been widely investigated as local drug delivery systems. Multiple drugs can be simultaneously incorporated into one EFM to create synergistic effects, reduce side effects, and play their respective roles in the complex physiological processes of tissue regeneration and postoperative adhesion prevention. Due to the versatile electrospinning techniques, sustained and programmed release behaviors of multiple drugs could be achieved by modulating the structure of the EFMs and the location of the drugs. In this review, various multidrug incorporation approaches based on electrospinning are overviewed. In particular, the advantages and limitations of each drug incorporation technique, the methods to control drug release and the effect of one drug release on another are discussed. Then the applications of multidrug-loaded EFMs in regenerative medicine, including wound healing, bone regeneration, vascular tissue engineering, nerve regeneration, periodontal regeneration and adhesion prevention are comprehensively reviewed. Finally, the future perspectives and challenges in the research of multidrug-loaded EFMs are discussed.


Philips Intellivue NMT module: precision and performance improvements to meet the clinical requirements of neuromuscular block management.
The variability or inaccuracy of acceleromyographic measurements could interfere with the interpretation of the train-of-four (TOF) ratio during neuromuscular block (NMB) recovery. This study evaluated the precision and performance of the Philips Intellivue NMT module (NMT) before (part 1) and after (part 2) several technical upgrades (i.e., firmware upgrade, new cable, and hand adapter) that were recently available. Two cohorts of 30 patients who were scheduled to undergo rhino/septoplasty under general anesthesia were included in the study. TOF ratios were recorded simultaneously every 15 s on both hands with the NMT and a TOF-Watch SX installed inside a SL TOF-Tube (TWX). Before rocuronium was administered and once final responses were stabilized, the average of the four successive measurements that determined the baselines and repeatability coefficients were compared using a z test. Simultaneous measurements were recorded at different NMB stages: onset, depth of NMB after intubation, when TWX recovered TOF count 2, TOF ratios 0.5 and 0.9, and when NMT recovered TOF ratio 0.9. The results were compared using a Student t test; p < 0.05 was considered significant. The NMT repeatability coefficients obtained in part 1 were significantly higher than with the TWX, they were significantly lower in part 2. Initially, the NMT significantly overestimated NMB recovery at every stage. Conversely, in the second part of the study, no difference reached statistical significance. With the recent upgrades and the new hand adapter, the NMT provided similar results compared with the TWX, Their implementation should be recommended in clinical practice.


[Comparison of the Effect of Autologous Serum on Therapy Resistant Corneal Erosions and Ulcers on the Corneal Graft vs. the Patient's Own Cornea].
The aim of this study is to compare the healing of corneal epithelial defects or ulcers on the corneal graft in comparison with the patient's own cornea after treatment with 100%, undiluted autologous serum eye drops. In a retrospective study over 7 years, we analysed 263 treatments with autologous serum eye drops of persistent corneal epithelial defects (erosions [88%] vs. ulcers [12%]). We compared the epithelial healing tendency of patients with defects on their own cornea (51.9%) vs. patients who had previously undergone penetrating keratoplasty (48.1%). Complete epithelial healing during the 28 days of treatment was considered as therapeutic success. In addition, the recurrence rate of the epithelial defects after finishing the therapy was analysed. 88.2% of the epithelial defects healed during 28 days of therapy. The recurrence rate during follow-up was 5.1%. There was no significant difference with respect to success rate between corneal defects on the patient's own cornea (87.8%) and on the graft (88.6%; p = 0.137). There was a significantly lower success rate for corneal ulcers (74.2%) than for erosions (90.3%; p < 0.001). The recurrence rate of erosions was 4.4%, vs. 4.3% in ulcers during follow-up. The results of our study suggest that autologous serum eye drops are a non-invasive and safe alternative treatment for persistent corneal epithelial defects - with no significant difference in patients with a defect on their own cornea vs. defects on the corneal graft. The success rate, but not the recurrence rate, is significantly worse in ulcers than in erosions.


Superparamagnetic iron oxide particles and positive enhancement for myocardial perfusion studies assessed by subsecond T1-weighted MRI.
Superparamagnetic iron oxide particles (SPIOs) are usually referred to as T2 MR contrast agents, reducing signal intensity (SI) on T2-weighted MR images (negative enhancement). This study reports the original use of SPIOs as T1-enhancing contrast agents, primarily assessed in vitro, and then applied to an in vivo investigation of a myocardial perfusion defect. Using a strongly T1-weighted subsecond MR sequence with SPIOs intravenous (IV) bolus injection, MR imaging of myocardial vascularization after reperfusion was performed, on a dog model of coronary occlusion followed by reperfusion. Immediately after the intravenous bolus injection of 20 mumol/kg of SPIOs, a positive signal intensity enhancement was observed respectively, in the right and left ventricular cavity and in the nonischemic left myocardium. Moreover, compared to normal myocardium, the remaining ischemic myocardial region (anterior wall of the left ventricle) appeared as a lower and delayed SI enhancing area (cold spot). Mean peak SIE in the nonischemic myocardium (posterior wall) was significantly higher than in the ischemic myocardium (anterior wall) (110 +/- 23% vs. 74 +/- 22%, Mann-Whitney test alpha < 1%, n1 = 6, n2-n1 = 0, U > 2). In conclusion, the T1 effect of SPIOs at low dose, during their first intravascular distribution, suggests their potential use as positive markers to investigate the regional myocardial blood flow and some perfusion defects such as the "no-reflow phenomenon."


Amiloride in ouabain-induced acidification, inotropy and arrhythmia: 23Na & 31P NMR in perfused hearts.
The increase in intracellular sodium (Nai), resulting from inhibition of the Na/K ATPase by cardiac glycosides, is known to increase calcium influx via Na(+)-Ca2+ exchange, and thereby increase contractility. This increase in intracellular Ca2+ has been related to the development of intracellular acidification and enhanced activity of the Na(+)-H+ exchanger as a measure by the cell to prevent further acidification. Thus, the efflux of the H+ ions results in an additional increase in Nai. This may subsequently lead to an increased rate of Ca2+ influx and therefore to the potentiation of the effects of cardiac glycosides. To assess the role of Na(+)-H+ exchange in the mechanism of ouabain action in the beating heart we used amiloride, a known inhibitor of Na(+)-H+ exchange. Isolated rat hearts were perfused with either ouabain (50 microM) alone (n = 8, Group I), amiloride (1.0 mM) + ouabain (50 microM) (n = 8, Group II), or amiloride (1.0 mM) alone as a control group (n = 4, Group III). 23Na and 31P NMR spectroscopy were used to assess the changes in Nai and intracellular pH (pHi), respectively, while simultaneous and continuous monitoring of left ventricular pressure was carried out. Perfusion with both ouabain alone (Group I) or ouabain + amiloride (Group II), resulted in a time dependent increase in Nai levels, reaching (within 25 mins) a maximum of 200 +/- 7% of control in Group I, and 170 +/- 10% of control in Group II. Concurrently, a mild but significant decrease in pHi was observed in both groups. This decrease, however, was significantly higher in Group II compared to Group I (0.34 pH units vs. 0.19 pH units, respectively; P less than 0.05), suggesting that inhibition of Na(+)-H+ exchange by amiloride limits the recovery from ouabain-induced intracellular acidification. While developed pressure gradually increased in Group I to a maximum of 268 +/- 52% of control, the addition of amiloride in Group II substantially reduced the positive inotropic effect. Ventricular fibrillation (VF) developed in three of the eight hearts in Group I within 10-13 mins after the addition of ouabain. Interestingly, the rate of Nai increase in hearts that sustained VF was significantly higher compared to those without VF (mean slope 10.1 +/- 2.11 vs. 3.9 +/- 1.0, respectively; P less than 0.0001). Ventricular fibrillation did not develop in Group II or III.(ABSTRACT TRUNCATED AT 400 WORDS)


Spirituality in geriatric palliative care.
This article presents an overview of spirituality as an essential domain of geriatrics palliative care, and provides guidelines for clinicians to diagnose spiritual distress and to integrate spirituality into their clinical practice.


A case of two connected stents deployed during iStent inject W surgery.
We report a case with two connected stents ejected simultaneously during an iStent inject W surgery, a modified second-generation iStent Trabecular Micro-Bypass System. A 57-year-old woman with primary open-angle glaucoma underwent a combined cataract and iStent inject W surgery in her left eye. After the trabecular meshwork/Schlemm's canal was pierced by the trocar of injector, the delivery button was pressed a first time, but the stent was not ejected. After the button was pressed a second time, connected two stents were ejected. After removing the dislocated stents from the anterior chamber, two stents were implanted into the desired places using another injector. Except for mild hyphema, no postoperative complication occurred. Stereomicroscopic observation showed that the two stents were connected by a broken trocar shaft. An X-ray showed that the trocar shaft was broken at the part referred to as the "sprayed trocar". Scanning electron microscopy showed that the surface features of the broken trocar and trocar tip represented tensile failure. Although rare, considering that the damage was seen at the structurally weak part (i.e., sprayed trocar), the same phenomenon can happen. For patient safety, surgeons are recommended to inspect the device when the deployment of either the first or second stent is unsuccessful during the iStent inject surgery.


[Fibrochondrogenesis].
Fibrochondrogenesis is a lethal form of dwarfism similar to thanatophoric dwarfism. It is distinguished radiologically by the widening of the metaphyses of the long bones, and, on lateral x-ray of the spine, by a median fissure of the body of the vertebra without any loss of vertebral height. The condition is inherited an autosomal recessive. A study of growing cartilage confirms that this disease is a distinct entity as there is fibrosis of the cartilage which is never present in thanatophoric dwarfism or in the different forms of achondrogenesis.


Chromosome studies on blood lymphocytes of men occupationally exposed to cadmium.
Chromosome studies were carried out on peripheral blood lymphocytes from a population of 40 men occupationally exposed to cadmium salts for periods up to 34 years, and on 13 on-site controls. Although four chromatid interchanges were observed in 3740 cells from the exposed workers and none in the 1243 cells from controls, there was no significant difference in aberration frequency between the two groups. Possible reasons for contrasting findings on the chromosome-damaging effects of cadmium in other published reports are discussed, and the possibility that heavy metals might act synergistically to enhance the mutagenicity of other compounds present in the environment is considered.


Multimodality imaging in primary hyperparathyroidism.
Institutional variations in parathyroid adenoma localisation are largely dictated by local experience and availability of imaging investigations, with no consensus on the optimal approach. This review evaluates the role of multiple imaging techniques in primary hyperparathyroidism and highlights their advantages and limitations in different clinical contexts. A clinico-radiological review of parathyroid imaging techniques is illustrated with example cases and data from the literature. These include high-resolution ultrasound, 99mTc-sestamibi planar scintigraphy with and without thyroid subtraction techniques, integrated 99mTc-sestamibi single-photon-emission computed tomography (SPECT)/computed tomography (CT), four-dimensional (4D) CT, and other techniques, such as magnetic resonance imaging, integrated 18F-choline/11C-methionine positron-emission tomography (PET)/CT and angiographic selective venous sampling. The crucial role of parathyroid embryological and gross anatomy in informing the surgical approach to parathyroidectomy is discussed. Finally, a systematic approach to imaging is proposed to maximise the accuracy of imaging localisation of parathyroid lesions, which is crucial for optimal patient management.


Surface coil with reduced specific absorption rate for rat MRI at 7 T.
A scaled-down slotted surface radio frequency (RF) coil was built, and the specific absorbance rate (SAR) in 100 mg of tissue (SAR100 mg) produced in a rat brain phantom was computed at 7 T. A slotted coil 2-cm in diameter with six circular slots was developed. Its theoretical and experimental performance was computed and compared using the signal-to-noise ratio (SNR) expression and phantom images obtained with a spin echo sequence. Electromagnetic simulations were performed using the finite integral method with saline sphere and rat brain phantoms. SAR100 mg was computed for the circular coil, by varying its radius, and was also computed for the slotted coil. The slotted coil quality factor gave a twofold increment over the circular coil, and noise was reduced by 17%. The experimental SNR of the slotted coil produced a 30% improvement for points near the coil plane. The theoretical and experimental results showed substantial agreement. Axial map histograms and profiles showed greater SAR100 mg values for the circular coil than for the slotted coil. The slotted surface coil offers improved performance and low SAR100 mg for rat brain imaging at 7 T. This approach may be used with new RF coils to investigate SAR in humans.


Specific inhibition of gene expression and transactivation functions of hepatitis B virus X protein and c-myc by small interfering RNAs.
With a view to developing therapeutic strategies against hepatocellular carcinoma (HCC), we have recently shown that co-expression of c-myc and the X protein of hepatitis B virus (HBx) resulted in the development of HCC in the X-myc transgenic mice. We now show in cell culture-based studies that small interfering RNA (siRNA) corresponding to HBx and c-myc can regulate expression and transactivation of the target genes. Expression vectors for small hairpin RNAs (shRNAs) against two different regions each of the HBx and c-myc open reading frames were constructed and their regulatory effects were investigated in COS-1 cells. A dose-dependent specific inhibition in the expression levels of HBx and c-myc was observed with individual shRNAs. Further, the recombinantly expressed shRNAs also blocked the transactivation functions of their cognate genes. Though each shRNA worked at a different efficiency, the inhibitory effects with two different shRNAs were cumulative. These results appear promising for developing a siRNA-based therapy for HCC.


Inhibition of plasminogen activator production in organ cultures by cycloheximide.
The production of tissue plasminogen activator (TPA) in rat tongue organ cultures is strongly inhibitied by low concentrations of the protein synthesis inhibitor cycloheximide. TPA production is fully resumed after the removal of cycloheximide from the culture medium.


Selective microstructural integrity impairments of the anterior corpus callosum are associated with cognitive deficits in obstructive sleep apnea.
There is some evidence that obstructive sleep apnea (OSA) patients have white matter integrity abnormality in the corpus callosum (CC). However, whether the CC subregions are differentially affected in OSA is largely unknown. Twenty patients with OSA and 24 well-matched healthy controls were enrolled and underwent diffusion tensor imaging (DTI) and clinical and cognitive assessments. DTI tractography was used to reconstruct the CC which was divided into five subregions. Intergroup differences in multiple diffusion metrics of each CC subregion and their correlations with clinical and cognitive parameters were tested. In comparison with healthy controls, OSA patients exhibited white matter integrity alterations in the anterior CC, characterized by increased radial diffusivity (RD) in the subregion 1 and decreased fractional anisotropy (FA) along with increased mean diffusivity (MD) and RD in the subregion 2. Moreover, we found that the lower microstructural integrity in the anterior CC was correlated with worse prospective memory and sustained attention in OSA patients. These findings indicate that the selective impairments of the anterior CC may help clarify the neural correlates of cognitive impairments in OSA.


Near-infrared hyperspectral imaging in tandem with partial least squares regression and genetic algorithm for non-destructive determination and visualization of Pseudomonas loads in chicken fillets.
Hyperspectral imaging was exploited for its potential in direct and fast determination of Pseudomonas loads in raw chicken breast fillets. A line-scan hyperspectral imaging system (900-1700 nm) was employed to obtain sample images, which were then further corrected, modified and processed. The prepared images were correlated with the true Pseudomonas counts of these samples using partial least squares (PLS) regression. To enhance model performance, different spectral extraction approaches, spectral preprocessing methods as well as wavelength selection schemes based on genetic algorithm were investigated. The results revealed that extraction of mean spectra is more efficient for representation of sample spectra than computation of median spectra. The best full wavelength model was attained based on spectral images preprocessed with standard normal variate, and the correlation coefficients (R) and root mean squared errors (RMSEs) for the model were above 0.81 and below 0.80 log10 CFU g(-1), respectively. In development of simplified models, wavelengths were selected by using a proposed two-step method based on genetic algorithm. The best model utilized only 14 bands in five segments and produced R and RMSEs of 0.91 and 0.55 log10 CFU g(-1), 0.87 and 0.65 log10 CFU g(-1) as well as 0.88 and 0.64 log10 CFU g(-1) for calibration, cross-validation and prediction, respectively. Moreover, the prediction maps offered a novel way for visualizing the gradient of Pseudomonas loads on meat surface. Hyperspectral imaging is demonstrated to be an effective tool for nondestructive measurement of Pseudomonas in raw chicken breast fillets.


Efficacy of biventricular pacing for dialysis-related hypotension due to idiopathic dilated cardiomyopathy.
A 45-year-old man who had been undergoing maintenance hemodialysis for end-stage renal failure, caused by chronic glomerulonephritis 4 years before, was admitted to our hospital for biventricular pacemaker implantation (BVP). Ten years ago, he was diagnosed with idiopathic dilated cardiomyopathy, and had been suffering from dialysis-related hypotension (DRH) due to low cardiac function over the past year. An electrocardiogram revealed complete left bundle branch block with a QRS duration of 180 ms, and echocardiography showed moderate hypokinesis of the left ventricular wall and systolic asynchronized motion of the septum and free wall. After BVP, the left ventricular ejection fraction had increased from 29% to 40%, and the transmitral rapid left ventricular filling (E wave) and atrial contraction (A wave) ratio (E/A) had improved from 1.3 to 1.0. Before and after BVP, we measured hemodynamic parameters during hemodialysis by successive echocardiography. Before BVP, systemic vascular resistance had decreased, cardiac output had not changed, and hypotension was noted. In contrast, after BVP, cardiac output had increased and systemic vascular resistance had not changed, which caused an increase in blood pressure. We conclude that BVP improved the cardiac function which resulted in an improvement in dialysis-related hypotension (DRH).


Effects of Long-Term DME Control With 0.2 µg/Day Fluocinolone Acetonide Implant on Quality of Life: An Exploratory Analysis From the FAME Trial.
Exploratory investigation of the effect of diabetic macular edema (DME) control with the 0.2 µg/day fluocinolone acetonide (FAc) intravitreal implant on quality of life (QOL) outcomes. Post-hoc analysis of patients from the FAME study who received the FAc implant and had answered the National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ-25) at baseline and Year 3 (N = 324). Patients were divided into quartiles (area under the curve [AUC]-central subfield thickness [CST]/day; n = 81/quartile). NEIVFQ-25 and best-corrected visual acuity (BCVA) changes were analyzed per quartile during a period of 3 years. NEI-VFQ-25 scores were significantly higher in patients with low AUC-CST/day (Quartiles 1 [P < .001] and 2 [P = .004]). Increases in NEIVFQ-25 subscale scores correlated with AUC-CST/day quartiles. BCVA significantly improved in patients with the lowest AUC-CST/day (Quartiles 1 and 2 [P < .001]). There was a positive and sustained correlation between the long-term control of DME and patient-reported QOL outcomes for up to 3 years following a single FAc implant in patients with controlled DME. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:658-667.].


Podocyte-derived extracellular vesicles mediate renal proximal tubule cells dedifferentiation via microRNA-221 in diabetic nephropathy.
Podocyte injury is a key event in the initiation of Diabetic nephropathy (DN). Tubulointerstitium, especially the proximal tubule has been regarded as a target of injury. In the present study, we showed that podocytes induced dedifferentiation of proximal tubular epithelial cells(PTECs) in high-glucose conditions and extracellular vesicles (EVs) mediates the interaction. Then we extracted and identified these EVs derived from podocytes as exosome, further, the EVs induced PTECs dedifferentiation. Total microRNA(miRNA) expression of podocyte-derived EVs was extracted and miR-221 expression was remarkably increased. By making use of the miRNA gain- and loss-of-function approaches, we observed that miR-221 mediated PTECs dedifferentiation. In addition, a dual-luciferase reporter assay confirmed that miR-221 direct target DKK2, which was an inhibitor of Wnt signaling, and overexpression of miR-221 significantly resulted in β-catenin nuclear accumulation. Moreover, we regulated the expression of β-catenin and demonstrated that miR-221 in EVs mediated proximal tubule cells injury through Wnt/β-catenin signaling. Furthermore, inhibition of miR-221 in diabetic mice reversed the abnormal expression of PTECs dedifferentiation related protein. These findings provide unique insights in the mechanisms of proximal tubule cell injury in diabetic nephropathy.


Changes in the national prevalence of asthma and coronavirus disease 2019 fatality: A population-based cross-sectional study.
The coronavirus disease 2019 (COVID-19) mitigation and containment strategies implemented by each country can influence the prevalence of asthma and its fatality. To analyze the trend of asthma prevalence and COVID-19 fatality in children and adults with asthma. The prevalence of asthma and fatalities were compared among the peaks of 5 pandemic waves in Mexico. Among patients with COVID-19, the prevalence rates of asthma among children were as follows: wave I, 3.5%; wave II, 2.6%; wave III, 2.2%; wave IV, 2.4%; and wave V, 1.9% (P for trend < .001); the prevalence rates of asthma among adults were as follows: wave I, 2.5%; wave II, 1.8%; wave III, 1.5%; wave IV, 1.7%; and wave V, 1.6% (P for trend < .001). The rates of fatality because of COVID-19 among individuals with asthma were as follows: wave I, 8.9%; wave II, 7.7%; wave III, 5.0%; wave IV, 0.9%; and wave V, 0.2% (P for trend < .001). The prevalence rates of asthma and fatalities from COVID-19 suggest a gradual reduction throughout the pandemic in Mexico.


Expanded nursing care for contraceptive use.
Nursing actions to promote contraceptive self-care are described. Orem's self-care theory was used to develop assessment tools and to plan nursing actions.


Relationship between serum indirect bilirubin and prostate volume in patients with benign prostatic hyperplasia: a cross-sectional study.
Due to its anti-oxidative effects, bilirubin may protect against a spectrum of diseases. However, the role of bilirubin in patients with benign prostatic hyperplasia (BPH) is poorly explored. This study aimed to investigate the cross-sectional associations between serum indirect bilirubin (IBIL) and prostate volume (PV) in patients with BPH. The medical records of 722 BPH patients were retrospectively analyzed. Body mass index (BMI) was calculated as body weight (kg)/height (m)2. PV was obtained as height (cm) × width (cm) × length (cm) × π/6. Other biochemical indexes were measured by the automatic biochemical analyzer. A univariable linear regression analysis was performed to detect confounders. The IBIL-PV relationship was examined using unadjusted and covariate-adjusted regression models. Furthermore, a segmented linear regression was conducted to analyze the linear trend of IBIL levels and PV. Finally, the sensitivity analysis was stratified by BMI and low-density lipoprotein cholesterol (LDL-C) cutoffs. In this study, the mean age of the patients was 68 (range, 43-93) years. By univariable line regression test, we observed that PV was positively correlated with age, BMI, and LDL-C (β=0.113, 0.096, and 0.135, respectively). IBIL was negatively associated with PV in full adjusted model in men age ≤75 years (β=-1.01; 95% CI: -1.81, -0.22; P=0.01). A statistically significant inverse trend was observed between serum IBIL intervals and PV in patients aged ≤75 years (adjusted for age, BMI, and LDL-C, P for trend =0.015). In sensitivity analysis, significantly negative IBIL-PV relationship only existed in men with normal BMI (adjusted β=-1.328; 95% CI: -2.467, -0.190; P=0.022), overweight men (adjusted β=-1.296; 95% CI: -2.519, -0.074; P=0.038), and men with normal LDL-C level (adjusted β=-1.017; 95% CI: -1.869, -0.164; P=0.019). IBIL is negatively associated with PV in the non-obese population ≤75 years with normal LDL-C. These results suggest that higher serum IBIL possibly provides a degree of protection to BPH by mitigating oxidative stress (OS) related to aging and lipid peroxidation. Nevertheless, these preliminary findings from a single-center, retrospective study have limitations and need to be confirmed by future studies.


Nursing research--taking an active interest.
This paper discusses the issues raised by the still unfolding transformation of nurse education attitudes to research, from the traditional stance--that it was something that other people do--to the realization that quality research is central to the development of the profession and its competitive survival into the 21st century. In particular, the problems and challenges presented by the Higher Education Funding Council for England research assessment exercise, and the policy of the funding council, are examined. Research in schools of nursing is reviewed under the headings of funding, contracts, support, discipline, publication and staff recruitment and retention, to attempt to identify those approaches most likely to yield a research output of an acceptable volume and quality.


Basic parameters of saccadic eye movements--differences between unmedicated schizophrenia and affective disorder patients.
Smooth pursuit eye movement (SPEM) dysfunctions are considered a biological marker for schizophrenia and have been studied widely. In contrast, saccadic eye movements have received less attention, although disturbances have been described previously. Basic neurophysiologic parameters of saccades in schizophrenics, especially in unmedicated patients, have not been studied extensively. Saccadic eye movements of 38 unmedicated schizophrenic patients, 32 patients with major depression and 42 non-psychiatric controls were examined using high-resolution infrared oculography. Two large-amplitude saccadic tasks were presented. The groups were compared on peak velocity, reaction time and accuracy. Peak velocity was significantly increased in schizophrenic patients. Depressive patients had a significantly longer reaction time. Both patient groups needed more corrective saccades to reach the target than controls. Peak velocity distinguishes unmedicated schizophrenic patients from depressive patients and normal controls. This could be explained by deficits of the prefrontal cortex in the inhibitory control of saccades. Our findings suggest that schizophrenia affects not only SPEM but also saccadic eye movements.


Migraine and intranasal contact point headache: is there any connection?
It has been suggested that contact point can trigger headache in individuals with migraine. In this article, we review the anatomy of the sinonasal cavity. We then define contact points and discuss the pathophysiology of contact point headaches. We propose a theory to explain the relationship between migraines and contact points. We close by presenting our personal casuistic in the surgical treatment of patients with contact point and refractory headaches. In migraineurs with contact point, surgery may improve the headaches.


Minnesota Multiphasic Personality Inventory prediction of intellectual changes following cardiac surgery.
One hundred two cardiac surgery patients were tested with the Minnesota Multiphasic Personality Inventory (MMPI) preoperatively and 98 of these patientts (two diet, two were untestable) were tested both pre- and postoperatively with the Wechsler Adult Intelligence Scale, Bender-Gestalt, and the Wechsler Memory Scale. A large number of the patients obtained preoperative "neurotic"-type MMPI profiles. Postoperative deficits in intellectual ability were slight for the group as a whole, however, there was marked within-group variance. The MMPI was not found to be useful as a predictor of postoperative intellectual changes.


Development and validation of a standardized method for contouring the brachial plexus: preliminary dosimetric analysis among patients treated with IMRT for head-and-neck cancer.
Although Radiation Therapy Oncology Group protocols have proposed a limiting dose to the brachial plexus for patients undergoing intensity-modulated radiotherapy for head-and-neck cancer, essentially no recommendations exist for the delineation of this structure for treatment planning. Using anatomic texts, radiologic data, and magnetic resonance imaging, a standardized method for delineating the brachial plexus on 3-mm axial computed tomography images was devised. A neuroradiologist assisted with identification of the brachial plexus and adjacent structures. This organ at risk was then contoured on 10 consecutive patients undergoing intensity-modulated radiotherapy for head-and-neck cancer. Dose-volume histogram curves were generated by applying the proposed brachial plexus contour to the initial treatment plan. The total dose to the planning target volume ranged from 60 to 70 Gy (median, 70). The mean brachial plexus volume was 33 +/- 4 cm(3) (range, 25.1-39.4). The mean irradiated volumes of the brachial plexus were 50 Gy (17 +/- 3 cm(3)), 60 Gy (6 +/- 3 cm(3)), 66 Gy (2 +/- 1 cm(3)), 70 Gy (0 +/- 1 cm(3)). The maximal dose to the brachial plexus was 69.9 Gy (range, 62.3-76.9) and was >/=60 Gy, >/=66 Gy, and >/=70 Gy in 100%, 70%, and 30% of patients, respectively. This technique provides a precise and accurate method for delineating the brachial plexus organ at risk on treatment planning computed tomography scans. Our dosimetric analysis suggest that for patients undergoing intensity-modulated radiotherapy for head-and-neck cancer, brachial plexus routinely receives doses in excess of historic and Radiation Therapy Oncology Group limits.


Turkey origin reovirus-induced immune dysfunction in specific pathogen free and commercial turkey poults.
Recently, pathogenesis studies, using genetically distinct turkey-origin reoviruses (TRVs), revealed that poults infected with certain TRV isolates had moderate to severe bursal atrophy, suggesting virus-induced immune dysfunction. In order to characterize the effect of TRV infection on the turkey immune system, classical assays were undertaken to quantify the humoral and cell-mediated immune responses in small Beltsville and broad-breasted white poults infected with the TRV isolate NC/SEP-R44/03. A marked effect on the cutaneous basophil hypersensitivity response, and on the antibody response to Newcastle disease virus (NDV) exposure, was noted in commercial and specific pathogen free (SPF) poults inoculated with NC/SEP-R44/03 at three days of age. Moderate to severe bursal atrophy, similar to that noted previously in SPF poults, occurred in commercial poults inoculated at three days of age. This immune dysfunction and bursal atrophy was not present in commercial poults inoculated at three weeks of age.


Characteristics of corticomuscular coupling during wheelchair Tai Chi in patients with spinal cord injury.
Wheelchair Tai Chi (WCTC) has been proved to have benefits for the brain and motor system of spinal cord injury (SCI) patients. However, the characteristics of corticomuscular coupling during WCTC are scarcely known. We aimed to investigate changes following SCI on corticomuscular coupling, and further compare the coupling characteristics of WCTC with aerobic exercise in SCI patients. A total of 15 SCI patients and 25 healthy controls were recruited. The patients had to perform aerobic exercise and WCTC, while healthy controls needed to complete a set of WCTC. The participants accomplished the test following the tutorial video in a sitting position. The upper limb muscle activation was measured from upper trapezius, medial deltoid, biceps brachii and triceps brachii with surface electromyography. Cortical activity in the prefrontal cortex, premotor cortex, supplementary motor area and primary motor cortex was simultaneously collected by functional near-infrared spectroscopy. The functional connectivity, phase synchronization index and coherence values were then calculated and statistically analyzed. Compared to healthy controls, changes in functional connectivity and higher muscle activation were observed in the SCI group. There was no significant difference in phase synchronization between groups. Among patients, significantly higher coherence values between the left biceps brachii as well as the right triceps brachii and contralateral regions of interest were found during WCTC than during aerobic exercise. The patients may compensate for the lack of corticomuscular coupling by enhancing muscle activation. This study demonstrated the potential and advantages of WCTC in eliciting corticomuscular coupling, which may optimize rehabilitation following SCI.


Diabetes prevalence and metabolic risk profile in an unselected population visiting pharmacies in Switzerland.
Diabetes represents one of the major health challenges in Switzerland, and early diagnosis and treatment is mandatory to prevent or delay diabetes-related morbidity and mortality. For the purpose of identifying affected individuals, early screening in pharmacies is a valuable option. In this survey, we aimed to determine blood glucose and metabolic control in an unselected population of individuals visiting Swiss pharmacies. The subjects responded to a short questionnaire and underwent a single capillary blood glucose test for screening purposes. They were classified as normal, indeterminate, impaired fasting glucose, and diabetes according to predefined blood glucose levels. A total of 3135 individuals (mean age 56 years) in 18 cantons were screened in November 2010; of these, 4.2% (95% confidence interval [CI] 3.5-4.9) had previously been diagnosed with diabetes. Diabetes was newly diagnosed in 1.9% (95% CI 1.5-2.4), and 11.5% (95% CI 10.4-12.6) had impaired fasting glucose. Subjects with impaired glucose control had an increased body mass index, a frequent family history of diabetes, hypertension, hypercholesterolemia, smoking, and a low level of physical activity. Prevalence of impaired glucose control was different between the French/Italian-speaking part of Switzerland (new diabetes 4.9%; impaired fasting glucose 12.7%) and the German-speaking part (new diabetes 1.9%; impaired fasting glucose 10.3%). Our study shows a 6.1% prevalence of diabetes, of which about a third (1.9%) was previously undiagnosed, and 11.5% had impaired fasting glucose. Therefore, screening initiatives in pharmacies may be suitable for detecting people with undiagnosed diabetes.


Insecticide-treated nets against malaria vectors and polystyrene beads against Culex larvae.
In Parasitology Today in 1985, Curtis and Lines, and Curtis and Minjas presented the ideas of insecticide-treated nets and polystyrene beads for mosquito control. The former idea has grown to be a major component of the strategy for malaria prevention, especially in Africa. However, although polystyrene beads have been demonstrated to work extremely well, they have yet to be taken up on a major scale.


Activation of protein kinase C and the involvement of prostaglandin E2 in the inhibition of osteosarcoma-derived cell alkaline phosphatase activity.
We present evidence for the presence of specific, high-affinity binding sites for tritiated phorbol 12,13-dibutyrate on osteosarcoma-derived (HT-3) cells. Activation of protein kinase C by a phorbol ester resulted in an inhibition of alkaline phosphatase activity and the accumulation of prostaglandin E2. Indomethacin blocked prostaglandin E2 production and enhanced alkaline phosphatase activity. These data suggest that prostaglandin E2 is enhanced by activation of protein kinase C, and in turn, alkaline phosphatase activity is reduced.


How and why RNA genomes are (partially) ordered in viral capsids.
There is a long and productive progression of X-ray crystallographic and electron microscopy studies establishing the structures of the spherical/icosahedral and cylindrical/helical capsids of a wide range of virus particles. This is because of the high degree of order - down to the Angstrom scale - in the secondary/tertiary/quaternary structure of the proteins making up the capsids. In stark contradistinction, very little is known about the structure of DNA or RNA genomes inside these capsids. This is because of the relatively large extent of disorder in the confined DNA or RNA, due to several fundamental reasons: topological defects in the DNA case, and secondary/tertiary structural disorder in the RNA case. In this article we discuss the range of partial order associated with the encapsidated genomes of single-stranded RNA viruses, focusing on the contrast between mono-partite and multi-partite viruses and on the effects of sequence-specific and non-specific interactions between RNA and capsid proteins.


Temperature modulates phototrophic periphyton response to chronic copper exposure.
Streams located in vineyard areas are highly prone to metal pollution. In a context of global change, aquatic systems are generally subjected to multi-stress conditions due to multiple chemical and/or physical pressures. Among various environmental factors that modulate the ecological effects of toxicants, special attention should be paid to climate change, which is driving an increase in extreme climate events such as sharp temperature rises. In lotic ecosystems, periphyton ensures key ecological functions such as primary production and nutrient cycling. However, although the effects of metals on microbial communities are relatively well known, there is scant data on possible interactions between temperature increase and metal pollution. Here we led a study to evaluate the influence of temperature on the response of phototrophic periphyton to copper (Cu) exposure. Winter communities, collected in a 8 °C river water, were subjected for six weeks to four thermal conditions in microcosms in presence or not of Cu (nominal concentration of 15 μg L(-1)). At the initial river temperature (8 °C), our results confirmed the chronic impact of Cu on periphyton, both in terms of structure (biomass, distribution of algal groups, diatomic composition) and function (photosynthetic efficiency). At higher temperatures (13, 18 and 23 °C), Cu effects were modulated. Indeed, temperature increase reduced Cu effects on algal biomass, algal class proportions, diatom assemblage composition and photosynthetic efficiency. This reduction of Cu effects on periphyton may be related to lower bioaccumulation of Cu and/or to selection of more Cu-tolerant species at higher temperatures.


Printable and recyclable carbon electronics using crystalline nanocellulose dielectrics.
Electronic waste can lead to the accumulation of environmentally and biologically toxic materials and is a growing global concern. Developments in transient electronics-in which devices are designed to disintegrate after use-have focused on increasing the biocompatibility, whereas efforts to develop methods to recapture and reuse materials have focused on conducting materials, while neglecting other electronic materials. Here, we report all-carbon thin-film transistors made using crystalline nanocellulose as a dielectric, carbon nanotubes as a semiconductor, graphene as a conductor and paper as a substrate. A crystalline nanocellulose ink is developed that is compatible with nanotube and graphene inks and can be written onto a paper substrate using room-temperature aerosol jet printing. The addition of mobile sodium ions to the dielectric improves the thin-film transistor on-current (87 μA mm-1) and subthreshold swing (132 mV dec-1), and leads to a faster voltage sweep rate (by around 20 times) than without ions. The devices also exhibit stable performance over six months in ambient conditions and can be controllably decomposed, with the graphene and carbon nanotube inks recaptured for recycling (>95% recapture efficiency) and reprinting of new transistors. We demonstrate the utility of the thin-film transistors by creating a fully printed, paper-based biosensor for lactate sensing.


Management of unilateral head and neck carcinoma of unknown primary: Retrospective analysis of the impact of postoperative radiotherapy target volumes.
We compared the outcome of postoperative unilateral cervical nodes radiotherapy (UL-RT) vs bilateral cervical nodes plus total mucosal irradiation (COMP-RT) in the management of head and neck carcinoma of unknown primary (HNCUP). HNCUP, defined by the absence of primary despite a PET-CT combined with a panendoscopy, were treated with curative intent by initial ipsilateral neck dissection. Sixty-nine patients with unilateral HNCUP were included: 23 received UL-RT while 46 received COMP-RT. Carcinologic outcomes and long-term quality of life (QOL) according to the QOL Questionnaire for Head and Neck 35 were assessed. Within 6.3 years of median follow-up, there was no significant difference in primary tumor emergence rate (P = .68), cervical node recurrence rate (P = .34), or overall survival (P = .33) between UL-RT and COMP-RT groups. A trend toward QOL improvement was observed in the UL-RT group. UL-RT seems to provide similar outcomes as COMP-RT in unilateral HNCUP management.


Preimplantation genetic diagnosis for Y-linked diseases: why not?
The introduction of intracytoplasmic sperm injection (ICSI) has allowed men with severe oligozoospermia and non-obstructive azoospermia to achieve fertilization and parenthood. A significant number of these men have translocation defects affecting the long arm of the Y chromosome. Chromosomal anomalies are considered to be a major contributor to the genetic risks of fertilization treatment by ICSI. The most frequently documented genetic cause of male infertility is Y-chromosome deletions, which have been shown to be transmitted to 100% of male offspring. It is appropriate to open a debate on the use of preimplantation genetic diagnosis with ICSI for severe male factor associated with Y-chromosome aberrations.


Differential effects of lithocholate on rat neutrophil activation.
Neutrophils (PMNs) may be exposed to high concentrations of biliary products during cholestasis and other hepatic disorders. We have previously reported that bile and certain bile salts enhance superoxide (O2-) release from neutrophils activated with phorbol myristate acetate (PMA) (Dahm et al.: Toxicol. Appl. Pharmacol. 95, 82, 1988), suggesting that PMN oxidative metabolism might be altered in toxicoses or disease states characterized by elevations in serum bile salts and other biliary products. In the present study, we characterized the priming effect of lithocholate for O2- release and also examined the effects of lithocholate on enzyme release from PMNs. PMNs preincubated with lithocholate at concentrations which did not directly stimulate O2- release (3-100 microM) and activated with PMA released greater amounts of O2- than controls exposed to PMA alone, illustrating a priming effect. O2- release from lithocholate-primed PMNs rose sharply between 5 and 10 min after PMA addition and then ceased between 10 and 30 min. The priming effect of lithocholate toward PMA-activated PMNs was reduced approximately 50% by washing PMNs after lithocholate addition and was not dependent on extracellular Ca2+, although removal of Ca2+ from the incubation buffer enhanced the cytotoxicity of lithocholate toward PMNs. In Ca2(+)-supplemented medium, lithocholate primed PMNs for O2- release when formyl-methionyl-leucyl-phenylalanine (FMLP, 10(-8)-10(-6) M) or calcium ionophore, A23187 (10(-7) or 10(-6)M), was used to activate PMNs. Lithocholate (100 microM) by itself had only marginal effects on release of lysozyme or beta-glucuronidase from PMNs. However, lithocholate (100 microM) inhibited beta-glucuronidase release from FMLP-stimulated PMNs to near-baseline levels. When FMLP was added to PMNs prior to lithocholate, beta-glucuronidase release was not reduced as it was when the order of addition was the reverse. Lithocholate had no effect on PMA-stimulated lysozyme release. These results indicate that lithocholate has different actions on PMN O2- release and enzyme release and suggest that lithocholate might exert its action on the PMN plasma membrane.


Carbonic anhydrase generates a pH gradient in Bombyx mori silk glands.
Silk is a protein of interest to both biological and industrial sciences. The silkworm, Bombyx mori, forms this protein into strong threads starting from soluble silk proteins using a number of biochemical and physical cues to allow the transition from liquid to fibrous silk. A pH gradient has been measured along the gland, but the methodology employed was not able to precisely determine the pH at specific regions of interest in the silk gland. Furthermore, the physiological mechanisms responsible for the generation of this pH gradient are unknown. In this study, concentric ion selective microelectrodes were used to determine the luminal pH of B. mori silk glands. A gradient from pH 8.2 to 7.2 was measured in the posterior silk gland, with a pH 7 throughout the middle silk gland, and a gradient from pH 6.8 to 6.2 in the beginning of the anterior silk gland where silk processing into fibers occurs. The small diameter of the most anterior region of the anterior silk gland prevented microelectrode access in this region. Using a histochemical method, the presence of active carbonic anhydrase was identified in the funnel and anterior silk gland of fifth instar larvae. The observed pH gradient collapsed upon addition of the carbonic anhydrase inhibitor methazolamide, confirming an essential role for this enzyme in pH regulation in the B. mori silk gland. Plastic embedding of whole silk glands allowed clear visualization of the morphology, including the identification of four distinct epithelial cell types in the gland and allowed correlations between silk gland morphology and silk stages of assembly related to the pH gradient. B. mori silk glands have four different epithelial cell types, one of which produces carbonic anhydrase. Carbonic anhydrase is necessary for the mechanism that generates an intraluminal pH gradient, which likely regulates the assembly of silk proteins and then the formation of fibers from soluble silk proteins. These new insights into native silk formation may lead to a more efficient production of artificial or regenerated silkworm silk fibers.


Motilities of isolated and aggregated mice; a difference in ultradian rhythmicity.
Isolated mice display higher locomotor activity and greater sensitivity to d-amphetamine than aggregated mice. Ultradian motility rhythms can be shown to differ both quantitatively and qualitatively between isolated and aggregated mice.


Dithranol mediates pro-oxidative inhibition of polymorphonuclear leukocyte migration and lymphocyte proliferation.
Dithranol (0.01-1 micrograms/ml), but not the auto-oxidized form, caused a dose-related enhancement of the generation of reactive oxidants by leukoattractant-activated polymorphonuclear leukocytes (PMNL) in vitro. At the same concentrations dithranol inhibited both PMNL migration to leukoattractants and mitogen-stimulated mononuclear leukocyte (MNL) proliferation. Catalase (50-100 units/ml) protected both PMNL migration and MNL proliferation from dithranol whilst ascorbate and cysteine (1 mM), which maintain dithranol in the biologically active reduced state, potentiated the inhibition. To establish the molecular mechanism of the pro-oxidative activity of dithranol its effects on cytosolic protein kinase C (PKC) activity were investigated. Dithranol caused a dose-related activation of PKC by apparent substitution for 1,2-diolein. These results demonstrate that dithranol, but not its auto-oxidation products, activates PKC which in turn initiates the generation of reactive oxidants by PMNL. Since reactive oxidants are immunosuppressive the therapeutic mechanisms of dithranol may be related to pro-oxidative interactions of this agent with skin phagocytes.


Daytime restriction of feeding prevents illuminated night-induced impairment of metabolism and sleep in diurnal zebra finches.
We investigated whether nocturnal eating was causal to the impairment of metabolism and sleep disruption in diurnal animals exposed to illuminated nights. Adult zebra finches hatched and raised in 12 h light: 12 h darkness (LD) were exposed to 5-lux dim light at night (dLAN, two groups), with a control group maintained on LD. For the next 3 weeks, the food availability to one of the dLAN groups was restricted to the 12 h light period (dLAN -F); the other dLAN (dLAN +F) and LD groups were continued on ad lib feeding. In spite of similar food intakes, dLAN +F condition led to the fat accumulation and weight gain. These birds showed concurrent changes in hepatic expression of genes associated with carbohydrate and lipid metabolism, suggesting an enhanced gluconeogenesis and impaired fatty acids synthesis. Increased sirt1 mRNA levels indicated the activation of molecular mechanisms to counter-balance the metabolic damage under dLAN +F. Furthermore, reduced bout length and total duration of the nocturnal sleep suggested a poorer sleep in dLAN +F condition. Negative sleep effects of dLAN were supported by the lower hypothalamic expression of sleep promoting sik3 and camkii genes, and higher mRNA expression of awake promoting achm3 gene in dLAN +F, compared to the LD condition. Importantly, dLAN-induced negative effects in metabolism and sleep were alleviated in the dLAN -F group. These results suggest the role of timed feeding in alleviating the negative impact of illuminated nights in metabolism and sleep in diurnal zebra finches.


A randomized comparative dose-ranging study of interferon-alpha and mitomycin-C as an internal control in primary or recurrent superficial transitional cell carcinoma of the bladder.
To compare, in a phase II study, the activity and toxicity of three dose levels of interferon-alpha, and of mitomycin-C given intravesically (as an internal control to validate the results), the primary objective being to investigate the percentage of complete responses (complete disappearance of a marker lesion) induced by the three interferon-alpha dose levels on a marker lesion; a secondary objective was to compare the interferon-alpha doses for toxicity. In all, 115 patients were enrolled, with the inclusion criteria being multiple grade 1 or 2, stage Ta or T1, primary or recurrent transitional cell carcinoma of the bladder. Interferon-alpha (30, 50 and 80 MU) and mitomycin-C (40 mg) intravesical treatments were given as follows. Patients randomized to one of three interferon-alpha dose levels were treated weekly for 12 weeks. However, in week 9 (first cystoscopy after baseline) interferon-alpha treatment was stopped if there was a complete response or disease progression. Patients randomized to mitomycin-C were treated weekly for 8 weeks only and in week 9 underwent follow-up cystoscopy. Interferon-alpha at doses of 30, 50 and 80 MU gave response rates at 13 weeks of 19%, 33% and 41%, respectively. Although the response rates were higher for 50 and 80 MU than for 30 MU, the differences were not statistically significant. All three interferon-alpha groups had significantly lower response rates than the internal control, mitomycin-C (72%). The safety analysis showed that most of the adverse events were of mild to moderate severity. Adverse events were experienced by 37%, 37% and 48% of patients receiving 30, 50 and 80 MU interferon-alpha, respectively, and by 55% of patients receiving mitomycin-C. The corresponding rates for severe adverse events related to treatment were 9% for interferon-alpha and 10% for mitomycin-C. Ablative therapy with interferon-alpha was less effective than mitomycin-C in patients with superficial bladder cancer. Both drugs were well tolerated, although interferon-alpha appeared to have a slightly better overall safety profile.


Influence of age at diagnosis and duration of diabetes on the positivity of glutamic acid decarboxylase antibody in South-Brazilian type 1 diabetes mellitus.
To evaluate the influence of age of onset and duration of diabetes on the positivity of glutamic acid decarboxylase antibody (GADA) in South-Brazilian type 1 diabetes mellitus (DM) patients. GADA was evaluated in 92 patients with type 1 diabetes, in 147 gestational DM patients, and in 59 subjects with normal glucose tolerance. Type 1 patients with positive GADA (N = 44, 48%) were older at the onset of diabetes (22 ± 9 versus 18 ± 10 y, P = 0.043) and had a shorter DM duration (12 ± 8 versus 19 ± 9 y, P < 0.001), as compared with negative GADA patients. A logistic regression with antibody positivity as the dependent variable and diabetes duration as the independent variable, showed that the shorter diabetes duration was related to the presence of the antibody with an odds ratio (OR) = 5.6; (CI 95% = 2.1-14.6); P < 0.001. Another model, with age at diagnosis as the independent variable, did not show any association with antibody positivity. However, analysing only men, a shorter DM duration (OR = 6.5; CI = 1.7-24.0; P = 0.006), and also a higher age at diagnosis (OR = 5.5; CI = 1.5-21.0; P = 0.01) were significantly related to the antibody positivity. The performance of GADA was similar in up to 15 y of duration of DM (P = 0.78), but significantly diminished with higher duration (P = 0.001). GADA testing is a helpful tool in the diagnosis of type 1 DM starting in young adults and older individuals. Even though the positivity rate declines along the course of disease, it still provides useful information up to 15 y after the diabetes diagnosis.


Genetic investigation of the contribution of body composition to anorexia nervosa in an electronic health record setting.
Anorexia nervosa (AN) is a psychiatric disorder defined by anthropometric symptoms, such as low body weight, and cognitive-behavioral symptoms, such as restricted eating, fear of weight gain, and distorted body image. Recent studies have identified a genetic association between AN and metabolic/anthropometric factors, including body mass index (BMI). Although the reported associations may be under pleiotropic genetic influences, they may represent independent risk factors for AN. Here we examined the independent contributions of genetic predisposition to low body weight and polygenic risk (PRS) for AN in a clinical population (Vanderbilt University Medical Center biobank, BioVU). We fitted logistic and linear regression models in a retrospective case-control design (123 AN patients, 615 age-matched controls). We replicated the genetic correlations between PRSBMI and AN (p = 1.12 × 10-3, OR = 0.96), but this correlation disappeared when controlling for lowest BMI (p = 0.84, OR = 1.00). Additionally, we performed a phenome-wide association analysis of the PRSAN and found that the associations with metabolic phenotypes were attenuated when controlling for PRSBMI. These findings suggest that the genetic association between BMI and AN may be a consequence of the weight-related diagnostic criteria for AN and that genetically regulated anthropometric traits (like BMI) may be independent of AN psychopathology. If so, individuals with cognitive-behavioral symptomatology suggestive of AN, but with a higher PRSBMI, may be under-diagnosed given current diagnostic criteria. Furthermore, PRSBMI may serve as an independent risk factor for weight loss and weight gain during recovery.


[Prognostic value of the state of the heart atria in determination of the time of sinus rhythm preservation after correction of auricular fibrillation].
Data are presented from atrial vectorcardiograms of 130 patients with different forms of auricular fibrillation including an analysis of their parameters and a study of the catamnestic data following the elimination of auricular fibrillation, which permitted to develop prognostic criteria for determining the period of sinus rhythm preservation after this type of arrhythmia had been eliminated.


Chronic neck pain and muscle activation characteristics of the shoulder complex.
Neck pain is a very common musculoskeletal complaint in industrialized countries. Theoretically, chronic neck pain is thought to possibly change biomechanics and muscle activation patterns of the shoulder complex, causing its pain and dysfunction in the long term. The present cross-sectional study was conducted to compare shoulder complex muscle activation characteristics in patients with chronic non-specific neck pain, compared to healthy participants. Twenty patients with chronic neck pain and twenty healthy participants were recruited for the present study. Surface Electromyographic (sEMG) activity was recorded from four selected muscles (anterior and middle deltoid, upper and lower trapezius) during shoulder elevation with a predetermined load (25-30% of an individual's maximum voluntary exertion). Results revealed only two significant increased onset delays in the anterior and middle deltoid,and a peak delay in the upper trapezius in chronic neck pain patients. Furthermore, increased onset delay for other muscles and decreased peak normalized amplitude (MVE%) for all muscles were found in chronic neck pain patients; however, these findings were not statistically significant. There were relationships between chronic non-specific neck pain and the shoulder muscle activation characteristic; hence, the alteration may be considered a predisposing factor for the shoulder dysfunction in future studies.


Recognition of DNA abasic site nanocavity by fluorophore-switched probe: Suitable for all sequence environments.
Removal of a damaged base in DNA produces an abasic site (AP site) nanocavity. If left un-repaired in vivo by the specific enzyme, this nanocavity will result in nucleotide mutation in the following DNA replication. Therefore, selective recognition of AP site nanocavity by small molecules is important for identification of such DNA damage and development of genetic drugs. In this work, we investigate the fluorescence behavior of isoquinoline alkaloids including palmatine (PAL), berberine (BER), epiberberine (EPI), jatrorrhizine (JAT), coptisine (COP), coralyne (COR), worenine (WOR), berberrubine (BEU), sanguinarine (SAN), chelerythrine (CHE), and nitidine (NIT) upon binding with the AP nanocavity. PAL is screened out as the most efficient fluorophore-switched probe to recognize the AP nanocavity over the fully matched DNA. Its fluorescence enhancement occurs for all of the AP nanocavity sequence environments, which has not been achieved by the previously used probes. The bridged π conjugation effect should partially contribute to the AP nanocavity-specific fluorescence, as opposed to the solvent effect. Due to the strong binding with the AP nanocavity, PAL will find wide applications in the DNA damage recognition and sensor development.


Pharmacokinetics of single dose radium-223 dichloride (BAY 88-8223) in Japanese patients with castration-resistant prostate cancer and bone metastases.
This open-label, non-randomized, phase I study examined the pharmacokinetics (PK) and radiation dosimetry of a single dose of radium-223 in Japanese patients with castration-resistant prostate cancer (CRPC) and bone metastases. Six male Japanese patients (mean age 72.5 years, range 65-79 years) with histologically or cytologically confirmed stage IV adenocarcinoma of the prostate were recruited. A single IV dose of radium-223 was delivered intravenously (IV) via slow bolus over a 2-5 min period: Cohort 1 received 50 kBq/kg and Cohort 2 received 100 kBq/kg. Following IV injection, radium-223 was rapidly eliminated from the blood in a multi-phasic manner. The fraction of the injected activity of radium-223 retained in the whole body 24 h following injection was 85 %. Biodistribution results showed initial bone uptake was 52 % (range 41-57 %). The maximum activity of radium-223 in the bone was observed within 2 h of dosing. Activity of radium-223 passed through the small intestine within 24 h. No activity was detected in other organs. The major radiation dose from radium-223 was found in osteogenic cells; calculated absorbed doses in osteogenic cells and in the red marrow were 0.76 Gy/MBq and 0.09 Gy/MBq, respectively. In Japanese patients with CRPC and bone metastases, radium-223 (IV) achieved maximum activity in the bone rapidly and passed through the intestine within 24 h, without signs of activity in other organs. The PK profile and absorbed radiation dose in organs and tissues in Japanese patients were similar to data from non-Japanese patients. Trial registration identification: NCT01565746.


Practical proxies for tidal marsh ecosystem services: application to injury and restoration.
Tidal marshes are valued, protected and restored in recognition of their ecosystem services: (1) high productivity and habitat provision supporting the food web leading to fish and wildlife, (2) buffer against storm wave damage, (3) shoreline stabilization, (4) flood water storage, (5) water quality maintenance, (6) biodiversity preservation, (7) carbon storage and (8) socio-economic benefits. Under US law, federal and state governments have joint responsibility for facilitating restoration to compensate quantitatively for ecosystem services lost because of oil spills and other contaminant releases on tidal marshes. This responsibility is now met by choosing and employing metrics (proxies) for the suite of ecosystem services to quantify injury and scale restoration accordingly. Most injury assessments in tidal marshes are triggered by oil spills and are limited to: (1) documenting areas covered by heavy, moderate and light oiling; (2) estimating immediate above-ground production loss (based on stem density and height) of the dominant vascular plants within each oiling intensity category and (3) sampling sediments for chemical analyses and depth of contamination, followed by sediment toxicity assays if sediment contamination is high and likely to persist. The percentage of immediate loss of ecosystem services is then estimated along with the recovery trajectory. Here, we review potential metrics that might refine or replace present metrics for marsh injury assessment. Stratifying plant sampling by the more productive marsh edge versus the less accessible interior would improve resolution of injury and provide greater confidence that restoration is truly compensatory. Using microphytobenthos abundance, cotton-strip decomposition bioassays and other biogeochemical indicators, or sum of production across consumer trophic levels fails as a stand-alone substitute metric. Below-ground plant biomass holds promise as a potential proxy for resiliency but requires further testing. Under some conditions, like chronic contamination by organic pollutants that affect animals but not vascular plants, benthic infaunal density, toxicity testing, and tissue contamination, growth, reproduction and mortality of marsh vertebrates deserve inclusion in the assessment protocol. Additional metrics are sometimes justified to assay microphytobenthos, use by nekton, food and habitat for reptiles, birds and mammals, or support of plant diversity. Empirical research on recovery trajectories in previously injured marshes could reduce the largest source of uncertainty in quantifying cumulative service losses.


Non-concerted ITS evolution in fungi, as revealed from the important medicinal fungus Ophiocordyceps sinensis.
The internal transcribed spacer (ITS) of nuclear ribosomal DNA (nrDNA) has been widely used as a molecular marker in phylogenetic studies and has been selected as a DNA barcode for fungi. It is generally believed that nrDNA conforms to concerted evolution in most eukaryotes; however, intraindividual-intraspecific polymorphisms of this region were reported in various organisms, suggesting a non-concerted evolutionary process. In Ophiocordyceps sinensis, one of the most valuable medicinal fungi, a remarkable variation of the ITS region has been revealed. Some highly divergent sequences were thought to represent cryptic species, different species or genotypes in previous studies. To clarify the unusual ITS polymorphisms observed in O. sinensis, specific primers were designed to amplify ITS paralogs from pure cultures of both single-ascospore and tissue isolates in this study. All of the available ITS sequences, including those generated by this group and those in GenBank, were analyzed. Several AT-biased ITS paralogs were classified as pseudogenes based on their nucleotide compositions, secondary structures and minimum free energies of their 5.8S rRNAs, substitution rates, phylogenetic positions and gene expression analyses. Furthermore, ITS pseudogenes were amplified with specific primers from 10 of the 28 strains tested, including eight single-ascospore and two tissue isolates. Divergent ITS paralogs were proved to coexist in individual genomes, suggesting a non-concerted mechanism of evolution in the ITS region of O. sinensis. The hypotheses that divergent ITS paralogs represent cryptic or other species or different genotypes were thus rejected.


Enhanced complex local frequency elastography method for tumor viscoelastic shear modulus reconstruction.
The Mayo Clinic provides a magnetic resonance (MR) elastography software named MRE Wave, which uses the conventional local frequency elastography (LFE) method. However, MRE Wave is unable to supply complex viscoelasticity maps for elastography. We sought to improve the local frequency estimation algorithm used in LFE, which we refer to as the Enhanced Complex Local Frequency Elastography (EC-LFE) algorithm. The proposed algorithm uses wave equations under the hypotheses of being linear, isotropic, and locally homogeneous. Two 2D simulation models were used to investigate the accuracy and sensitivity of the EC-LFE algorithm for detecting small tumors. The corresponding statistical parameters were the relative root mean square (RMS) error and contrast-to-noise ratio (CNR). EC-LFE was investigated with two different parameter sets, one with an optimally chosen parameter ξ (EC-LFE Adj, for short) and the other with ξ = 0 (EC-LFE0). We compared the MRE Wave and the EC-LFE using series signal-to-noise (SNR) wave data. The elasticity RMS error of the MRE Wave software was about 1%, and that of the EC-LFE0 and EC-LFE Adj were about 0.2%. The elasticity standard deviation of the MRE Wave software was about 3% of the mean value, and those of the EC-LFE0 and EC-LFE Adj were about 1% of the mean value. The elasticity CNR value of EC-LFE0 reached 1.93 times that of the MRE Wave in the region of small tumors (less than 10-point sampling). The viscosity RMS errors of the EC-LFE0 could be less than 5%. Compared to conventional methods, the EC-LFE was more accurate and sensitive for small tumor detection and exhibited higher noise immunity. The improved algorithm output more parameters and outperformed than the MRE Wave, thereby rendering them more suitable for clinical applications.


The ubiquitin ligase TRIM32 promotes the autophagic response to Mycobacterium tuberculosis infection in macrophages.
Mycobacterium tuberculosis (Mtb) is known to evade host immune responses and persist in macrophages for long periods. A mechanism that the host uses to combat Mtb is xenophagy, a selective form of autophagy that targets intracellular pathogens for degradation. Ubiquitination of Mtb or Mtb-containing compartments is a key event to recruit the autophagy machinery and mediate the bacterial delivery to the lysosome. This event relies on the coordinated and complementary activity of different ubiquitin ligases, including PARKIN, SMURF1, and TRIM16. Because each of these factors is responsible for the ubiquitination of a subset of the Mtb population, it is likely that additional ubiquitin ligases are employed by macrophages to trigger a full xenophagic response during Mtb infection. In this study, we investigated the role TRIM proteins whose expression is modulated in response to Mtb or BCG infection of primary macrophages. These TRIMs were ectopically expressed in THP1 macrophage cell line to assess their impact on Mtb replication. This screening identified TRIM32 as a novel player involved in the intracellular response to Mtb infection, which promotes autophagy-mediated Mtb degradation. The role of TRIM32 in xenophagy was further confirmed by silencing TRIM32 expression in THP1 cells, which causes increased intracellular growth of Mtb associated to impaired Mtb ubiquitination, reduced recruitment of the autophagy proteins NDP52/CALCOCO2 and BECLIN 1/BECN1 to Mtb and autophagosome formation. Overall, these findings suggest that TRIM32 plays an important role in the host response to Mtb infection through the induction of autophagy, representing a promising target for host-directed tuberculosis therapies.


Subscores of the FAB differentiate frontotemporal lobar degeneration from AD.
To determine the clinical utility of the Frontal Assessment Battery (FAB), a short test of frontal lobe functions, in differentiating frontotemporal lobar degeneration (FTLD) from Alzheimer disease (AD). FAB total scores and subscores for 23 subjects with FTLD and 31 subjects with AD were compared for sensitivity, specificity, and positive predictive value. Concurrent validity of the FAB with the Mini-Mental State Examination (MMSE) and other scales was also assessed. The FAB did not have positive predictive value for FTLD. Total FAB scores did not differ between the FTLD and AD groups. However, three subtests of the FAB (mental flexibility, motor programming, and environmental autonomy) demonstrated significant differences between the two groups. Total FAB scores correlated with scores on the MMSE, a more general test of cognition. The Frontal Assessment Battery did not discriminate subjects with frontotemporal lobar degeneration from those with Alzheimer disease, though certain subtests may be helpful in differential diagnosis.


Qualitative and quantitative mass spectrometry imaging of drugs and metabolites.
Mass spectrometric imaging (MSI) has rapidly increased its presence in the pharmaceutical sciences. While quantitative whole-body autoradiography and microautoradiography are the traditional techniques for molecular imaging of drug delivery and metabolism, MSI provides advantageous specificity that can distinguish the parent drug from metabolites and modified endogenous molecules. This review begins with the fundamentals of MSI sample preparation/ionization, and then moves on to both qualitative and quantitative applications with special emphasis on drug discovery and delivery. Cutting-edge investigations on sub-cellular imaging and endogenous signaling peptides are also highlighted, followed by perspectives on emerging technology and the path for MSI to become a routine analysis technique.


QF-PCR as a substitute for karyotyping of cytotrophoblast for the analysis of chorionic villi: advantages and limitations from a cytogenetic retrospective audit of 44,727 first-trimester prenatal diagnoses.
Karyotyping on chorionic villous samples (CVS) includes the analysis of both cytotrophoblast (STC) and mesenchyme (LTC). This approach requires complex laboratory organization and trained technicians. The introduction of quantitative fluorescent polymerase chain reaction (QF-PCR) instead of conventional karyotyping in low-risk pregnancies opened its application in CVS analysis. Discordant QF-PCR and CVS cytogenetic results were reported, and strategies for CVS analysis were introduced to minimize this risk. The possibility to substitute the STC with QF-PCR was reported. The aim of this study is to evaluate benefits and limitations of the approach QF-PCR + LTC compared with the traditional method STC + LTC and to quantify the associated risks of false results. This study is based on a retrospective cytogenetic audit of CVS results (n = 44 727) generated by the STC + LTC analytic approach. False-negative risks related to true fetal mosaicism type IV, imprinting syndromes and maternal contamination in LTC were calculated. Compared with STC + LTC, QF-PCR + LTC approach is associated with a cumulative false-negative risk of ~1/3100-1/4400. Costs and reporting time of STC in a high-throughput cytogenetic lab are similar to a CE-IVD marked QF-PCR analysis. These results should be clearly highlighted in the pre-test counseling and extensively discussed with the couple prior to testing for informed consent.


Colon motility during a panic attack.
To document the temporal relationship between a panic attack and high amplitude propagating contractions. Colon manometry was used to discriminate between functional defecation problems and colon neuromuscular disease. By chance, the patent developed a panic attack during the test session. Coincident with the panic attack, there was a continuous series of high amplitude propagating contractions. There were 15 high amplitude propagating contractions over 45 minutes, initially at a rate of 4 per 10 minutes, gradually slowing to 1.5 per 10 minutes. These data may explain the cause for gastrointestinal distress and diarrhea in some patients with panic attacks.


Effect of acute saline volume expansion in the anaesthetised DeltaF508 cystic fibrosis mouse.
It has been suggested that CFTR Cl(-) channels in the renal inner medullary collecting duct may be involved in mediating increased renal salt excretion during extracellular fluid volume expansion. To investigate this hypothesis, in-vivo clearance experiments were performed comparing wild-type (WT) and DeltaF508-CFTR transgenic mice (cftr (tm2Cam)). Control animals were given a 0.1-ml bolus of 0.9% saline, followed by I.V. infusion at 0.3 ml x h(-1). Volume expansion was applied by infusing a 1-ml bolus of 0.9% saline followed by infusion at 0.6 ml x h(-1). No significant differences in renal NaCl handling between WT mice ( C(Na)=1.2 +/- 0.3 microl x min(-1), C(Cl)=4.0 +/- 0.5 microl x min(-1)) and DeltaF508-CFTR mice ( C(Na)=1.7 +/- 0.5 microl x min(-1), C(Cl)=4.1 +/- 0.8 microl x min(-1)) were observed under control conditions. Volume expansion resulted in large significant increases in NaCl clearance in both WT mice ( C(Na)=7.0 +/- 0.9 microl x min(-1), C(Cl)=12.0 +/- 0.6 microl x min(-1)) and DeltaF508-CFTR mice ( C(Na)=7.2 +/- 1.6 microl x min(-1), C(Cl)=11.0 +/- 2.2 microl x min(-1)). However, there was no significant difference between WT and DeltaF508-CFTR mice. In conclusion, renal NaCl excretion is not significantly different under basal conditions and during saline volume expansion in DeltaF508-CFTR mice. The data suggest that CFTR is not a physiologically important mediator of volume natriuresis.