Blockade of pulmonary stretch receptors reinforces diaphragmatic activity during high-frequency oscillatory ventilation.
During apneic periods elicited by high-frequency oscillatory ventilation (HFOV) a tonic diaphragmatic activity was observed, contrasting with the absence of diaphragmatic activity during apnea induced by lung inflation. To clarify the mechanism underlying the persistence of the diaphragmatic activity during HFOV-induced arrest of breathing the reflex responses to short periods of HFOV, and to periods of lung inflation with airway pressure (Paw) equal to the mean Paw and/or to maximal Paw during HFOV were examined both before and after the blockade of slowly adapting stretch receptors (SR) by inhalation of sulphur dioxide (SO2) in anaesthetized rabbits. In animals with intact SR, the HFOV-induced reflex apnea lasted longer than that induced by lung inflation, the associated diaphragmatic activity being in the most cases higher than the diaphragmatic activity during quiet expiration; inflation, however, completely inhibited diaphragmatic activity. After blockade of SR, spontaneous breathing continued during periods of lung inflation, i.e., the Hering-Breuer inflation reflex was abolished, whereas HFOV still led to a cessation of spontaneous breathing, the associated diaphragmatic activity even exceeding the level observed during quiet inspiration. From these results we conclude that only one part of the reflex response to HFOV is due to SR-stimulation and that in addition other vagal pulmonary receptors (irritant- and/or C-fibre-receptors) are involved. The stimulation of the latter counterbalances the concomitant stimulation of SR, giving rise to the tonic activity of the diaphragm.


Inhibitory stabilized network behaviour in a balanced neural mass model of a cortical column.
Strong inhibitory recurrent connections can reduce the tendency for a neural network to become unstable. This is known as inhibitory stabilization; networks that are unstable in the absence of strong inhibitory feedback because of their unstable excitatory recurrent connections are known as Inhibition Stabilized Networks (ISNs). One of the characteristics of ISNs is their "paradoxical response", where perturbing the inhibitory neurons with additional excitatory input results in a decrease in their activity after a temporal delay instead of increasing their activity. Here, we develop a model of populations of neurons across different layers of cortex. Within each layer, there is one population of inhibitory neurons and one population of excitatory neurons. The connectivity weights across different populations in the model are derived from a synaptic physiology database provided by the Allen Institute. The model shows a gradient of excitation-inhibition balance across different layers in the cortex, where superficial layers are more inhibitory dominated compared to deeper layers. To investigate the presence of ISNs across different layers, we measured the membrane potentials of neural populations in the model after perturbing inhibitory populations. The results show that layer 2/3 in the model does not operate in the ISN regime but layers 4 and 5 do operate in the ISN regime. These results accord with neurophysiological findings that explored the presence of ISNs across different layers in the cortex. The results show that there may be a systematic macroscopic gradient of inhibitory stabilization across different layers in the cortex that depends on the level of excitation-inhibition balance, and that the strength of the paradoxical response increases as the model moves closer to bifurcation points.


Combined Inhibition of Gαq and MEK Enhances Therapeutic Efficacy in Uveal Melanoma.
All uveal melanoma and a fraction of other melanoma subtypes are driven by activation of the G-protein alpha-q (Gαq) pathway. Targeting these melanomas has proven difficult despite advances in the molecular understanding of key driver signaling pathways in the disease pathogenesis. Inhibitors of Gαq have shown promising preclinical results, but their therapeutic activity in distinct Gαq mutational contexts and in vivo have remained elusive. We used an isogenic melanocytic cellular system to systematically examine hotspot mutations in GNAQ (e.g., G48V, R183Q, Q209L) and CYSLTR2 (L129Q) found in human uveal melanoma. This cellular system and human uveal melanoma cell lines were used in vitro and in in vivo xenograft studies to assess the efficacy of Gαq inhibition as a single agent and in combination with MEK inhibition. We demonstrate that the Gαq inhibitor YM-254890 inhibited downstream signaling and in vitro growth in all mutants. In vivo, YM-254890 slowed tumor growth but did not cause regression in human uveal melanoma xenografts. Through comprehensive transcriptome analysis, we observed that YM-254890 caused inhibition of the MAPK signaling with evidence of rebound by 24 hours and combination treatment of YM-254890 and a MEK inhibitor led to sustained MAPK inhibition. We further demonstrated that the combination caused synergistic growth inhibition in vitro and tumor shrinkage in vivo. These data suggest that the combination of Gαq and MEK inhibition provides a promising therapeutic strategy and improved therapeutic window of broadly targeting Gαq in uveal melanoma.See related commentary by Neelature Sriramareddy and Smalley, p. 1217.


The E3 Ubiquitin Ligase Fbxo4 Functions as a Tumor Suppressor: Its Biological Importance and Therapeutic Perspectives.
Fbxo4, also known as Fbx4, belongs to the F-box protein family with a conserved F-box domain. Fbxo4 can form a complex with S-phase kinase-associated protein 1 and Cullin1 to perform its biological functions. Several proteins are identified as Fbxo4 substrates, including cyclin D1, Trf1/Pin2, p53, Fxr1, Mcl-1, ICAM-1, and PPARγ. Those factors can regulate cell cycle progression, cell proliferation, survival/apoptosis, and migration/invasion, highlighting their oncogenic or oncogene-like activities. Therefore, Fbxo4 is defined as a tumor suppressor. The biological functions of Fbxo4 make it a potential candidate for developing new targeted therapies. This review summarizes the gene and protein structure of Fbxo4, the mechanisms of how its expression and activity are regulated, and its substrates, biological functions, and clinicopathological importance in human cancers.


Stroke models: strengths and pitfalls.
Recent editorials and reviews express disillusionment and sharp criticism with the contribution of animal experimental studies to stroke prevention and treatment. The basis for these comments appears to be a frustration with the absence of pharmacologic agents to effectively treat stroke patients despite considerable research efforts. In response to these nihilistic views, Zivin and Grotta (Stroke, 21 (1990) 981-983) have written a poignant rebuttle and Goldstein (Stroke, 21 (1990) 373-374) has outlined the considerable progress which has been achieved in experimental cerebral stroke research. It is our goal in the present discussion to highlight the strengths and to examine the potential pitfalls of stroke models, some of which may have contributed to the equivocal results obtained in testing pharmacologic agents. In addition, based on our own experience with a model of middle cerebral artery (MCA) occlusion in cats, we will describe the benefits of large versus small animal models for experimental stroke studies.


The effect of angiotensin receptor neprilysin inhibitor, sacubitril/valsartan, on central nervous system amyloid-β concentrations and clearance in the cynomolgus monkey.
Sacubitril/valsartan (LCZ696) is the first angiotensin receptor neprilysin inhibitor approved to reduce cardiovascular mortality and hospitalization in patients with heart failure with reduced ejection fraction. As neprilysin (NEP) is one of several enzymes known to degrade amyloid-β (Aβ), there is a theoretical risk of Aβ accumulation following long-term NEP inhibition. The primary objective of this study was to evaluate the potential effects of sacubitril/valsartan on central nervous system clearance of Aβ isoforms in cynomolgus monkeys using the sensitive Stable Isotope Labeling Kinetics (SILK™)-Aβ methodology. The in vitro selectivity of valsartan, sacubitril, and its active metabolite sacubitrilat was established; sacubitrilat did not inhibit other human Aβ-degrading metalloproteases. In a 2-week study, sacubitril/valsartan (50mg/kg/day) or vehicle was orally administered to female cynomolgus monkeys in conjunction with SILK™-Aβ. Despite low cerebrospinal fluid (CSF) and brain penetration, CSF exposure to sacubitril was sufficient to inhibit NEP and resulted in an increase in the elimination half-life of Aβ1-42 (65.3%; p=0.026), Aβ1-40 (35.2%; p=0.04) and Aβtotal (29.8%; p=0.04) acutely; this returned to normal as expected with repeated dosing for 15days. CSF concentrations of newly generated Aβ (AUC(0-24h)) indicated elevations in the more aggregable form Aβ1-42 on day 1 (20.4%; p=0.039) and day 15 (34.7%; p=0.0003) and in shorter forms Aβ1-40 (23.4%; p=0.009), Aβ1-38 (64.1%; p=0.0001) and Aβtotal (50.45%; p=0.00002) on day 15. However, there were no elevations in any Aβ isoforms in the brains of these monkeys on day 16. In a second study cynomolgus monkeys were administered sacubitril/valsartan (300mg/kg) or vehicle control for 39weeks; no microscopic brain changes or Aβ deposition, as assessed by immunohistochemical staining, were present. Further clinical studies are planned to address the relevance of these findings.


Hemophilus influenzae Infection's Association With Decreased Risk of Breast Cancer.
Hemophilus influenzae (H. influenzae) is a common cause of widespread bacterial infections and has been associated with the stabilization of the microbiome. The microbiome, through modulating systemic inflammation with possible upregulation of the NLRP3 inflammasome, may potentiate the development of breast cancer (BC). The purpose of this study was to therefore evaluate the correlation between previous H. influenzae infection and the incidence of BC. A large national database was used to collect International Classification of Disease Ninth and Tenth Codes to evaluate the incidence of BC between January 2010 and December 2019 in patients with and without H. influenzae history. A retrospective cohort study was performed where these groups of individuals were matched by age range, Charlson Comorbidity Index (CCI), and antibiotic treatment exposure. Significance and relative risk were obtained using standard statistical procedures. A total of 13,599 patients were matched by age range and CCI in both the experimental and control groups. BC incidence was 259 (1.905%) in the H. influenzae group compared to 686 (5.044%) in the control group (P < 2.2 × 10-16; odds ratio (OR) = 0.604, 95% confidence interval (CI): 0.553 - 0.660). Matching by antibiotic treatment exposure resulted in two groups of 3,189 patients, in which BC incidence was 98 (3.073 %) in the H. influenzae group compared to 171 (5.362%) in the control group (P < 2.2 × 10-16; OR = 0.584, 95% CI: 0.515 - 0.661). The study shows a statistically significant correlation between H. influenzae and a reduced incidence of BC. These results warrant further research regarding H. influenzae's role in upregulating the NLRP3 inflammasome and its potential role in BC prevention and treatment.


Pediatric atypical extraventricular neurocytoma: Clinical features and survival outcomes.
Extraventricular neurocytoma (EVN) in children is an extremely rare encountered tumor. Little information is available about the treatment and prognosis of this rare disease in children. This study was undertaken to elucidate the clinical-radiological characteristics and treatment outcomes of pediatric patients with atypical EVN. A retrospective review of patients' demographic features, treatment modalities, and outcomes in our institution from January 2011 to December 2019 was conducted. Seven consecutive children harboring atypical EVN in our center were included, with a male predominance (n = 5, 71.4%) and a mean age of 11.8 ± 4.9 years (range: 2-18 years). The lesions mainly involved the frontal (n = 4, 57.1%) and temporal lobes (n = 4, 57.1%). Gross total resection (GTR) was achieved in 6 patients (85.7%), and subtotal resection (STR) was achieved in the remaining patient (14.3%). All lesions demonstrated a high Ki-67 index (≧5%) and atypical features pathologically. Five patients (71.4%) received radiotherapy and/or chemotherapy after surgery. During follow-up, 5 patients (71.4%) experienced lesion progression, and 2 (14.3%) of them died. The median progression-free survival was 48 months. The prognosis of pediatric patients with atypical EVN was dismal after aggressive treatment. Most tumors progressed, and this progression was positively correlated with the Ki-67 index. Surgical excision is the main treatment modality for atypical EVN, and radiation/chemotherapy should also be introduced after surgery.


Prenatal diagnosis of fetal malformations by ultrafast magnetic resonance imaging.
Prenatal ultrasonography is the primary imaging modality in pregnancy as it allows direct real-time fetal examination. Antenatal magnetic resonance imaging (MRI) has so far been of limited clinical value owing to poor image quality. This was due to the long acquisition times that were needed to achieve a high enough spatial resolution for assessment of the small fetal anatomic structures resulting in severe motion artefacts. This problem has now been overcome by recent technical improvements. We present a case of fetal malformation (MURCS association), where an ultrafast T2-weighted RARE sequence (single shot fast spin echo sequence) provided images of excellent quality, which led to the correct antenatal diagnosis. MRI using this sequence can now be used for prenatal diagnosis and is thus likely to become an important adjunct to ultrasonography, especially in cases in which ultrasound findings are unclear of sonographic images are impaired by maternal obesity or oligohydramnios.


Predicting admission to post-acute inpatient rehabilitation in patients with acute stroke.
To identify predictors of admission to post-acute inpatient rehabilitation settings follow-ing acute care for stroke survivors in Taiwan. Prospective observation study. Stroke survivors (n = 558) admitted to acute care wards for inpatient rehabilitation (62% male; mean age 60.0 ± 12.2 years). The primary outcome was whether survivors were admitted to post-acute inpatient rehabilitation settings after discharge from acute care wards. Logistic regression model was adopted to examine the predictors of admission to post-acute inpatient rehabilitation. A receiver operating characteristic curve was drawn to compute the ability of the predictors to discriminate the outcome. Multivariate analysis results indicated Activity Measure Post-Acute Care "6-Clicks" Basic Mobility score to be the only significant predictor of admission to post-acute inpatient rehabilitation (odds ratio = 0.44, 95% confidence interval: 0.34-0.56). Receiver operating characteristic curve analysis results indicated that the cut-off point for Basic Mobility was 13 (standardized score: 33.99). This yielded a sensitivity value of 0.98 and a specificity value of 0.96 for determining the admission to post-acute inpatient rehabilitation. Activity Measure Post-Acute Care "6-Clicks" Basic Mobility subscale scores at admission for acute care can predict admission to post-acute inpatient rehabilitation for stroke survivors in Taiwan. This tool can aid clinicians in formulating adequate discharge plans at an early stage, and thus improve the quality of care.


Optimization of parameters in protein nitrogen unit precipitation procedure for allergenic extracts.
This work establishes the optimum conditions for the protein nitrogen unit (PNU) phosphotungstic acid (PTA) precipitation procedure for allergenic extracts. The volume of extract analyzed, the dilution of the extract prior to precipitation, the percent PTA in the precipitating solution, the washing of the precipitate, and the volume of concentrated HCl initially added to the extract were optimized, as they were found to be the factors which affected the amount of PTA precipitate obtained. Varying the digestion time, the digestion temperature, and the percent HCl in the 15% PTA precipitating solution did not cause detectable differences in the PNU values of the extracts studied.


The turnover of milkweed pollinia on bumble bees, and implications for outcrossing.
Bumble bees (Bombus spp.) picked up a pollen packet (pollinium) of milkweed (Asclepias syriaca L.) every 2-5 h, usually more rapidly on their feet than on their mouthparts. Pollinia were retained an average of slightly over one day on the mouthparts and one-quarter day on the feet. This long retention period enhances the possibility of outcrossing in this largely or completely self-incompatible species. Although many more pollinia were carried on the feet, the longer retention of those on the mouthparts resulted in their collective outcrossing potential exceeding that of pollinia on the feet. Once pollinia became attached to the bees (via their attachment mechanisms, the corpuscula), others often attached to the translator arms (connecting corpusculum with pollinia) of the first pollinia. Long strings of pollinia and corpuscula often resulted, but they frequently were shed down to a single corpusculum, which was usually retained for long periods (estimated retention time=12-43 days). During the middle and latter part of the flowering period about two-thirds of the bees' feet carried only a single corpusculum. Feet in this condition picked up extremely few pollinia and thus were largely unavailable as sites for pollen transfer. Having several single corpuscula on the feet greatly lowered the number of pollinia carried by a bee over the season. Single corpuscula occurred much less frequently on the mouthparts and were shed over 25 times as rapidly as those on the feet. Many more bumble bees moved between clones than did other possible diurnal pollinators, largely a result of being several times more abundant than all other visitors combined. This factor, plus their heavy pollinia load, suggests that they were the most important diurnal pollinators of these clones.


Cadmium accumulation and isotope fractionation in typical protozoa Tetrahymena: A new perspective on remediation of Cd pollution in wastewater.
Cadmium (Cd) pollution threatens water safety and human health, which has raised serious public concern. Tetrahymena is a model protozoan, possessing the potential to remediate Cd contaminated water given the rapid expression of thiols. However, the mechanism of Cd accumulation in Tetrahymena has not been well understood, which hinders its application in environmental remediation. This study elucidated the pathway of Cd accumulation in Tetrahymena using Cd isotope fractionation. Our results showed that Tetrahymena preferentially absorb light Cd isotopes, with Δ114/110CdTetrahymena-solution = -0.20 ± 0.02‰ ∼ - 0.29 ± 0.02‰, which implies that the intracellular Cd is probably in the form of Cd-S. The fractionation generated by Cd complexation with thiols is constant (Δ114/110CdTetrahymena-remaining solution ∼ -0.28 ± 0.02‰), which is not affected by the concentrations of Cd in intracellular and culture medium, nor by the physiological changes in cells. Furthermore, the detoxification process of Tetrahymena results in an increase in cellular Cd accumulation from 11.7% to 23.3% with the elevated Cd concentrations in batch Cd stress culture experiments. This study highlights the promising application of Cd isotope fractionation in Tetrahymena for the remediation of heavy metal pollution in water.


[The chronic critically ill patient from the cardiologist's perspective].
In recent years the prognosis and survival of chronic and acute heart failure (HF) patients has been steadily improving; however, many patients develop advanced chronic HF which is characterized by worsening of symptoms, unplanned hospital admission due to acute decompensation, development of complications, such as life-threatening arrhythmia and shorter life span. Optimal medical therapy is supplemented by interventional cardiology, cardiovascular implantable electronic devices (CIEDs), minimally invasive valve replacement or repair, circulatory mechanical support and heart transplantation. Medical indications and informed consent are essential prerequisites for successfully implementing treatment goals. For patients who are incapable of decisions a legally defined surrogate decision-maker has the same right to refuse or request the withdrawal of treatment as the patient would have if the patient had decision-making capability. As the use of circulatory mechanical support becomes increasingly more prevalent, ethical issues are likely to arise at an increasing rate, as will social and legal ramifications. The concept of turning off an implanted device as death nears is challenging because of ethical and technical concerns. The same holds true for CIEDs. A palliative care approach is applicable to heart failure patients and is particularly relevant to those with advanced disease. Palliative care should be integrated as part of a team approach to comprehensive HF care and should not be reserved for those who are expected to die within days or weeks.


Gray-scale three-dimensional sonography of thyroid nodules: feasibility of the method and preliminary studies.
The aim of the study was differential evaluation of new and classical sonographic features of benign thyroid nodules and thyroid cancer with three-dimensional gray-scale sonography and evaluation of the effectiveness of the thin-slice surface rendered images in comparison with multiplanar reformation (MPR) presentation. Fifty-four thyroid nodules were interactively evaluated with thin-slice smooth surface rendering: shape in the c-plane (parallel to the probe) and evaluation of echogenicity, margins and calcification/microcalcification-like echogenic foci in the a-plane (plane of the probe). Evaluation of the level of agreement in readers' interpretation and between sonographic techniques was performed using the kappa statistic. Surface rendering permitted visualization of the shape of the nodule in the c-plane in all cases, in contrast to only up to 48% of cases in MPR evaluation. Lobulated nodule shape in the c-plane was 82-100% sensitive and 47-53% specific in diagnosis of carcinoma. Surface rendered images showed more calcification/microcalcification-like echogenic foci than MPR ones. The level of agreement between the observers in the evaluation of features of thyroid nodules and the agreement between features of thyroid nodules on MPR and surface-rendered images showed at least moderate reproducibility (kappa>or=0.41). Three-dimensional thin-slice surface rendering sonography appears to be a feasible and effective method for thyroid nodule evaluation.


Clinical and radiological characteristics of acute pulmonary embolus in relation to 28-day and 6-month mortality.
Patients with acute pulmonary embolism (PE) exhibit a wide spectrum of clinical and laboratory features when presenting to hospital and pathophysiologic mechanisms differentiating low-risk and high-risk PE are poorly understood. To investigate the prognostic value of clinical, laboratory and radiological information that is available within routine tests undertaken for patients with acute PE. Electronic patient records (EPR) of patients who underwent Computed Tomography Pulmonary Angiogram (CTPA) scan for the investigation of acute PE during 6-month period (01.01.2016-30.06.2016) were examined. Data was gathered from EPR for patients that met inclusion criteria and all CTPA scans were re-evaluated. Biochemical thresholds of low-grade and high-grade inflammation, serum CRP >10mg/L and >150mg/L and serum albumin concentrations <35g/L and <25 g/L, were combined in the Glasgow Prognostic Score (GPS) and peri-operative Glasgow Prognostic Score (poGPS) respectively. Neutrophil Lymphocyte ratio (NLR) was also calculated. Pulmonary Embolus Severity Index score was calculated. Of the total CTPA reports (n = 2129) examined, 245 patients were eligible for inclusion. Of these, 20 (8%) patients had died at 28-days and 43 (18%) at 6-months. Of the 197 non-cancer related presentations, 28-day and 6-month mortality were 3% and 8% respectively. Of the 48 cancer related presentations, 28-day and 6-month mortality were 29% and 58% respectively. On univariate analysis, age ≥65 years (p<0.01), PESI score ≥100(p = <0.001), NLR ≥3(p<0.001) and Coronary Artery Calcification (CAC) score ≥ 6 (p<0.001) were associated with higher 28-day and 6-month mortality. PESI score ≥100 (OR 5.2, 95% CI: 1.1, 24.2, P <0.05), poGPS ≥1 (OR 2.5, 95% CI: 1.2-5.0, P = 0.01) and NLR ≥3 (OR 3.7, 95% CI: 1.0-3.4, P <0.05) remained independently associated with 28-day mortality. On multivariate binary logistic regression analysis of factors associated with 6-month mortality, PESI score ≥100 (OR 6.2, 95% CI: 2.3-17.0, p<0.001) and coronary artery calcification score ≥6 (OR 2.3, 95% CI: 1.1-4.8, p = 0.030) remained independently associated with death at 6-months. When patients who had an underlying cancer diagnosis were excluded from the analysis only GPS≥1 remained independently associated with 6-month mortality (OR 5.0, 95% CI 1.2-22.0, p<0.05). PESI score >100, poGPS≥1, NLR ≥3 and CAC score ≥6 were associated with 28-day and 6-month mortality. PESI score ≥100, poGPS≥1 and NLR ≥3 remained independently associated with 28-day mortality. PESI score ≥100 and CAC score ≥6 remained independently associated with 6-month mortality. When patients with underlying cancer were excluded from the analysis, GPS≥1 remained independently associated with 6-month mortality. The role of the systemic inflammatory response (SIR) in determining treatment and prognosis requires further study. Routine reporting of CAC scores in CTPA scans for acute PE may have a role in aiding clinical decision-making regarding treatment and prognosis.


Audit of prehospital thrombolysis by general practitioners in peripheral practices in Grampian.
In the Grampian region early anistreplase trial (GREAT), domiciliary thrombolysis by general practitioners was associated with a halving of one year mortality compared with hospital administration. However, after completion of the trial and publication of the results, the use of this treatment by general practitioners declined sharply. To increase the proportion of eligible patients receiving timely thrombolytic treatment from their general practitioners. Practices in Grampian located > or = 30 minutes' travelling time from Aberdeen Royal Infirmary, where patients with suspected acute myocardial infarction were referred after being seen by general practitioners. AUDIT STANDARD: A call-to-needle time of 90 minutes, as proposed by the British Heart Foundation (BHF). Findings of this audit of pre-hospital management of acute myocardial infarction were periodically fed back to the participating doctors, when practice case reviews were also conducted. Of 414 administrations of thrombolytic treatment, 146 (35%) were given by general practitioners and 268 (65%) were deferred until after hospital admission. Median call-to-needle times were 45 (94% < or = 90) and 145 (7% < or = 90) minutes, respectively. Survival at one year was improved with prehospital compared with hospital thrombolysis (83% v 73%; p < 0.05). The proportion of patients receiving thrombolytic treatment from their general practitioners did not increase during the audit. In practices > or = 30 minutes from hospital, the BHF audit standard was readily achieved if general practitioners gave thrombolytic treatment, but not otherwise. Knowledge of the benefits of early thrombolysis, and feedback of audit results, did not lead to increased prehospital thrombolytic use. Additional incentives are required if general practitioners are to give thrombolytic treatment.


[Inhibition of permeability transition and myocardic reperfusion damage by cyclosporine A].
The results presented in this study indicate that the immunosuppressor cyclosporine A acts as a cardioprotective drug. This effect was analyzed during development of reperfusion-induced arrhythmias after 5 min period of coronary ligation in hearts of rats under anesthesia. The results indicate that cyclosporine inhibits Ca(2+)-induced mitochondrial damage; furthermore, when given before coronary occlusion, at a dose of 20 mg/kg, effectively protects against the high incidence of arrhythmias and the fall in blood pressure induced by reperfusion. In addition, it inhibits the delivery of lactic dehydrogenase and creatine kinase enzymes to the plasma. We propose that the protective effect could be related with its well documented action to restrain Ca(2+)-induced damage of mitochondrial functions.


Combining Chitosan, Stearic Acid, and (Cu-, Zn-) MOFs to Prepare Robust Superhydrophobic Coatings with Biomedical Multifunctionalities.
There is an urgent need to develop a series of multifunctional materials with good biocompatibility, high mechanical strength, hemostatic properties, antiadhesion, and anti-infection for applications in wound care. However, successfully developing multifunctional materials is challenging. In this study, two superhydrophobic composite coatings with good biocompatibility, high mechanical strength, strong antifouling and blood repellency, fast hemostasis, and good antibacterial activity are prepared on cotton fabric surface by simple, green, and low-cost one-step dip-coating technology. The results discussed in the manuscript reveals that the two superhydrophobic composite coatings can maintain good mechanical stability, strong water repellency, and durability under various types of mechanical damage, high-temperature treatment, and long-term strong light irradiation. The coatings also exhibit good repellency to various solid pollutants, highly viscous liquid pollutants, and blood. In vitro and in vivo hemostatic experiments show that both composite coatings have good hemostatic and anticlot adhesion properties. More importantly, this superhydrophobic coating prevents bacterial adhesion and growth and released Cu2+ and Zn2+ ions and chitosan to achieve bactericidal properties, thereby protecting injured skin from bacterial infection. The two superhydrophobic coatings enhance the antifouling, antiadhesion, hemostatic, and antibacterial functions of blood-repellent dressings and therefore have broad application prospects in medical and textile fields.


Simultaneous high-throughput determination of clenbuterol, ambroxol and bromhexine in pharmaceutical formulations by HPLC with potentiometric detection.
Potentiometric detection of clenbuterol, ambroxol and bromhexine in marketed pharmaceuticals was described in six isocratic HPLC systems. The podant- and macrocyclic-type neutral ionophores, N,N,N',N'-tetracyclohexyl-oxybis(o-phenyleneoxy)diacetamide (TOPA) and hexakis(2,3,6-tri-O-octyl)-alpha-cyclodextrin (OCD), were applied in poly(vinyl)chloride (PVC)-based liquid membrane electrodes. Both types of neutral ionophores improve the sensitivity for all mentioned drugs when compared with a tetrakis(p-chlorophenyl)borate (BOR)-based electrode as well as with single wavelength UV detection. Detection limits (S/N=3) of 2.6 x 10(-10) mol l(-1) (injected concentration) for the highly hydrophobic bromhexine were achieved with the TOPA-based electrode and a cyano reversed-phase (RP)-HPLC with Uptisphere UP5CN-25QS silica column (250 x 4.6 mm i.d.) eluted with acetonitrile (AcN)-ethanol-perchloric acid (1.66 mM) (60:2:38, v/v/v) (pH* 2.45). Comparable result was obtained with OCD-based electrodes and an XTerra RP18 hybrid silica-polymer column eluted with AcN-phosphoric acid (20 mM) (25:75, v/v) (pH* 2.60). In the mobile phases containing 60-75% v/v AcN or methanol, stable and reproducible response of both types of neutral ionophore-based electrodes was observed for at least 3 days. The results of the validated procedure for reliable simultaneous determination of the drugs in fortified representative samples of pharmaceuticals were also presented.


Patient preference and operating time for digital versus conventional impressions: a network meta-analysis.
Digital impression techniques have seen many advancements, with new hardware and software being developed each year. The technical advantages of these systems are real-time visualization, evaluation and archive, segmental capture, ease of recapture if necessary, economical in terms of no use of impression material or trays or disinfection, easy file transfer and communication with the laboratory. However patient satisfaction is one major factor that might influence the choice of impression technique. The aim of this network meta-analysis was to identify statistically the evidence on overall patient preferences relative to digital versus conventional impression techniques, in addition to the time taken in making these impressions. Randomized or prospective clinical studies were identified based on the inclusion criteria in PUBMED, DARE and COCHRANE databases; subsequently pertinent data were extracted. Risk of bias of the included studies was assessed using the Cochrane risk of bias tool and Newcastle-Ottawa scale. Heterogeneity amongst the studies in direct comparison was assessed by Chi-square and I2 tests using the Inverse variance heterogeneity model. Direct comparison estimates were derived by pooling the data from studies that compared the same intervention. Indirect comparison pooled estimates were derived by using the data amongst the studies, through a common comparator, using MetaXL software. Mean differences and Odds ratio at 95% confidence interval were used as the effect estimates, while inconsistencies were evaluated by H-statistics. GRADE working group approach was used to assess the quality of available evidence. Fourteen studies were included. Results from 11 studies on 471 patients (236-Digital; 235-conventional) were pooled for patient preference with 95% confidence interval. The Forest plot showed a pooled estimate of 31.23 [5.95, 163.87], showing a statistically significant number of patients favouring digital impressions. Results from 11 studies reported the time taken in 589 patients (278-digital; 311 conventional). The pooled estimate (2.72 [0.08, 5.32]) (95% confidence interval) showed a statistically significant increase in the time required to make digital impressions. The overall time taken in minutes for the interventions in the digital group in decreasing order were: LAVA Cos (8.14[3.64,12,26] (statistically significant); I tero (4.11[-1.02,9.24]; CEREC (0.34[-4.14,4.82]). There was an overall preference for digital impressions, although the time required is longer. The factors related to the digital system, the operator and the patient were studied, with recommendations forming a basis for possible hardware and software upgrades of the digital systems that can produce significant improvement in the acceptance rate for both the patient and the clinician.


Preparation of arsenic trioxide albumin microspheres and its release characteristics in vitro.
Arsenic trioxide albumin microspheres (As2O3-BSA-NS) were prepared by using methods of chemical cross-linking. The desirability function (DF), calculated according to the size (<1 microm) distribution, drug loading and drug trapping efficiency, was introduced as a total index for the microspheres formulation. Four factors, inculding W/O ratio, decentralization speed, BSA concentration and stirring stabilization time, were selected and arranged in an orthogonal experimental table. The release characteristic was studied by the drug release experiment in vitro. The four factors affected DF differently. Decentralization speed behaved as the maximum (P<0.01), followed by BSA concentration (P<0.05) and the W/O ratio dose (P<0.05). Stirring stabilization time did not influence DF (P>0.05). The release experiment in vitro showed that As2O3 in As2O3-BSA-NS was released more slower than pure As2O3. It was concluded that regular As2O3-BSA-NS may be prepared by the methods of chemical cross-linking, which was optimized by orthogonal experimental analysis of different factors, and the microspheres can release As2O3 slowly.


Lethal graft-versus-host reaction induced by parental cells in the clawed frog, Xenopus laevis.
(J X K)F1 hybrid frogs, Xenopus laevis, were produced by mating between the MHC-homozygous but distinct "J" and "K" group frogs. When the spleen or splenocytes from parental J were transplanted into the F1 frogs, a typical graft-versus-host reaction (GVHR) was induced that included wasting and death, accompanied by a prominent spleen enlargement and other histological changes in skin and lymphoid organs. To induce the reaction, sensitization against F1 cells prior to transfer of spleen was necessary. The reaction was accelerated when the parental donor cells had been sensitized by gamma-irradiated leukocytes from the F1 hybrid. The injection of presensitized triploid J splenocytes into F1 hybrids followed by ploidy analyses revealed that the donor cells constituted the major cell population in host lymphoid organs--such as the spleen, liver, and kidney--but not the thymus. These observations provide the first clear evidence in poikilothermic vertebrates for GVHR caused by parental lymphocytes.


Fourier analysis of spike train data.
A formal representation of nerve spike trains in the form of a sum of rectangular functions is proposed. This formal instantaneous frequency function can be Fourier analyzed. The resulting algorithm has the useful properties of spike by spike calculations and an insensitivity to the mean (carrier) spike rate. The technique is also useful for producing a smooth (filtered) reconstruction of a spike train.


Right ventricular dysfunction and the exercise limitation of chronic obstructive pulmonary disease.
This study examined right ventricular function during exercise in patients with chronic obstructive pulmonary disease to answer the following questions: Is there a significant correlation between oxygen consumption at maximal exercise and exercise right ventricular ejection fraction? Does the right ventricular ejection fraction response to exercise correlate with exercise changes in pulmonary artery pressure, total pulmonary resistance or pulmonary vascular resistance? Which combinations of cardiac, ventilatory and blood gas variables are the best predictors of oxygen consumption at maximal exercise? Twenty-six patients with stable chronic obstructive pulmonary disease performed symptom-limited supine bicycle exercise with simultaneous hemodynamic and radionuclide ventriculographic measurements. The oxygen consumption at maximal exercise correlated with the exercise right ventricular ejection fraction (n = 21, r = 0.66; p less than 0.005), exercise stroke volume (r = 0.68; p less than 0.001), exercise cardiac output (r = 0.77; p less than 0.00005) and exercise ventilation (r = 0.85; p less than 0.00001). The change in right ventricular ejection fraction from rest to exercise correlated inversely with the change from rest to exercise in total pulmonary resistance (r = -0.51; p less than 0.05) but not with the change in mean pulmonary pressure (r = -0.37) or in pulmonary vascular resistance (r = 0.09). Multivariate analysis showed that the variables giving the highest combined correlation with oxygen consumption were ventilation and right ventricular ejection fraction (r = 0.95, adjusted r2 = 0.88). These results suggest that exercise oxygen consumption of patients with chronic obstructive pulmonary disease is related to right ventricular systolic function, exercise right ventricular dysfunction is related, in part, to abnormal exercise total pulmonary resistance, and exercise limitation in chronic obstructive pulmonary disease occurs as a result of the dynamic interaction between disordered right heart function and ventilation.


Legionella gratiana sp. nov. isolated from French spa water.
During an epidemiologic survey, an unidentified strain of Legionella was isolated from water of a thermal spa in France. The strain (Lyon 8420412) had the cultural and biochemical characteristics typical of the genus Legionella. In direct immunofluorescence tests, the strain reacted weakly with fluorescein-conjugated antisera prepared against L. bozemanii serogroups 1 and 2, L. longbeachae serogroups 1 and 2 and L. anisa, and failed to react with sera prepared against 36 other species or serogroups. A fluorescein-conjugated antiserum prepared against strain Lyon 8420412 reacted strongly with the homologous strain and only weakly with the above-mentioned species. The cell-wall fatty acid profile, with a predominance of hexadecenoic (16:1) and hexadecanoic (16:0) acids, ubiquinone Q10 as the major quinone and a characteristic protein electrophoresis profile suggested that the isolate was different from other Legionella species. In DNA-DNA hybridization experiments, the strain was distinct from all named Legionella species, and from all unnamed species currently under study at the Centers for Disease Control. The name Legionella gratiana is proposed for the new species (type strain Lyon 8420412; CDC 1242). A serologic survey of antibodies reacting against L. gratiana indicated that personnel or patients at the spa therapy centre where the organism was isolated had higher antibody titres than a control population.


Facial electroneurography. Standardization of electrode position.
Electroneurography is now regarded as a valuable method for quantitatively assessing facial nerve function. Controversy, however, still surrounds some aspects of the technique because of the large number of associated variables. This study establishes by experiment the optimum site for both the recording and stimulating electrodes and recommends that this be adopted as a standard to ensure consistency in results between different study groups.


Affinity labelling of human transcortin.
The binding site of transcortin has been studied by using bromoacetyltestosterone and bromoacetylated derivatives of progesterone which were monohydroxylated at different positions of the steroid nucleus. Specificity of affinity labelling was demonstrated by the displad cortisol analog was added to a [3H]cortisol-transcortin complex solution. The binding site crevice was found to be very narrow in the vicinity of the A and B rings of steroid since 2alpha-hydroxyprogesterone, 6alpha- or 6beta-bromoacetoxyprogesterone and dexamethasone could not displace bound cortisol. A specific affinity labelling was obtained with 11alpha-bromoacetoxyprogesterone, 16alpha-bromoacetoxyprogesterone and 17beta-bromoacetyltestosterone. The results of the affinity labelling by these hormone analogs suggested that one methionine and one histidine residues were located within the active site:methionine might interact with the 11beta-hydroxyl group and histidine with the 20 keto group of cortisol.


[Association between arthritis, functional disability and quality of life using a structural equation].
To establish a conceptual model that links arthritis, functional disability in activities of daily living, and quality of life (QoL). A multicentre, cross-sectional, observation study was performed. The location of the arthritis (presence/absence) was recorded. Disability was measured using the Health Assessment Questionnaire Disability Index and the QoL determined using the EQ-5D-3 Level questionnaire. The relationship between the arthritis, disability, and the QoL was evaluated using the structural equation model (SEM). 965 patients with arthritis (mean age=64 years, with 75% females). Arthritis: mean areas affected: 2.8. Areas most frequently affected: knees (67%); lumbar spine (60%) and cervical spine (45%). QoL: The majority of patients did not mention serious problems in the five domains assessed. Disability: «other activities» (mean=1.2); «reach» (mean=1.1) and «walking» (mean=1.0) were the categories that demonstrated greater disability. The SEM showed arthritis, disability and QoL as associated latent variables. Although 92% of the QoL explained the disability, only 5% of the disability was due to the presence/absence of arthritis. The global model that describes arthritis as a cause of disability, and disability was affecting the QoL, had a reasonable goodness of fit (CMIN/DF=5.42; RMR=0.026; RMSEA=0.069). Functional disability can explain the decrease in QoL. In theory, arthritis is closely related with disability and QoL, but the model did not mange to fully explain this link. As statistical techniques required good measurement models to correctly determine relationships, conventional medical records seem to be insufficient for this purpose. Other valid measurements of arthritis are needed to provide tests of its direct effect on disability and QoL.


Distribution of GABAergic perikarya and terminals in the centers of the higher auditory pathway of the chicken.
The distribution of presumed GABAergic neurons and axon terminals in nuclei of the higher auditory pathway of the chicken was investigated by immunocyto-chemical methods employing antisera to the rate-limiting enzyme of GABA synthesis, glutamic acid decarboxylase, and to GABA. In the mesencephalic auditory center (MLD) about 20% of the cells reveal immunoreactivity. In contrast, the thalamic relay station nucleus ovoidalis is devoid of immunostained somata. This nucleus contains a high density of punctate immunoreactive structures presumed to be GABAergic axon terminals. In the auditory forebrain center field L and the auditory portions of the hyperstriatum ventrale, up to 8% of the cells were immunopositive. These neurons were significantly smaller than estimated from measurements of the overall cell population in these nuclei. From the two-dimensional arrangement of immunopositive neurons it is suggested that the GABAergic system in the avian auditory telencephalon consists of two separate groups of neurons: one subgroup mediating local inhibitory interactions, the other responsible for lateral inhibition between different frequency representations.


Response of chickpea genotypes to Agrobacterium-mediated delivery of Chickpea chlorotic dwarf virus (CpCDV) genome and identification of resistance source.
Chickpea stunt disease caused by Chickpea chlorotic dwarf virus (CpCDV) (genus Mastrevirus, family Geminiviridae) is the most important biotic stress affecting chickpea crops worldwide. A survey conducted on the incidence of stunt disease clearly revealed high incidence of the disease with severe symptom expression in both indigenous and imported genotypes. To manage the disease in a sustainable way, resistant genotypes need to be bred by adopting objective and precise assessment of the disease response of chickpea genotypes. At present, evaluation of CpCDV resistance is conducted on the basis of natural infection in the field, which is bound to be erroneous due to vagaries in vector population. To circumvent the above problems, we devised an agroinoculation technique that involves the delivery of viral genomic DNA through Agrobacterium tumefaciens. An objective scoring system assigning quantitative value to different symptoms has been evolved to assess the response of chickpea genotypes to CpCDV inoculation. Using the inoculation and scoring techniques, we screened 70 genotypes, which helped in differentiating field resistance that is more due to resistance to vector feeding than resistance to the virus.


Ca2+-dependent and -independent mechanisms of ischaemia-evoked release of [3H]-dopamine from rat striatal slices.
1. Ischaemia was induced by 5 min of deprivation of glucose and an additional 5 min of deprivation of glucose and oxygen from Mg(2+)-free artificial cerebrospinal fluid in vitro. 2. During the ischaemic period, 11 +/- 1.5% of the total [3H]-dopamine ([3H]-DA) was released into the incubation medium. 3. Ischaemia-evoked release of [3H]-DA from striatal slices was attenuated by tetrodotoxin (TTX), MgSO4, dizocilpine, ketamine, 6,7-dinitroquinoxaline-2,3-dione (DNQX) or carbetapentane. 4. Release of [3H]-DA was attenuated by verapamil, omega-conotoxin GVIA and dantrolene. 5. Nomifensin inhibited the ischaemia-induced release of [3H]-DA. 6. Omission of Ca(2+) from incubation media potentiated ischaemia-evoked [3H]-DA release. The inhibitory effect of nomifensin was potentiated in Ca(2+)-free incubation media. 7. These results suggest that ischaemia induces release of [3H]-DA by dual mechanisms; one is Ca(2+)-dependent exocytosis and the other is reversal of transporter.


Relationship of blood cholesterol and apoprotein B levels to angiographically defined coronary artery disease in young males.
Coronary heart disease is mainly caused by the effects of obstruction to blood flow in the coronary arteries from discrete mural lesions that encroach into the lumen and usually occur in arteries that are involved by atherosclerosis. Even though the level of certain lipoproteins is indisputably related to the degree of this atherosclerotic involvement of the coronary arteries, the question of whether lipoproteins are also associated with the obstructive lesions remains uncertain. This study addressed the question in 53 males (age, 44.6 +/- 4.9 y) with premature coronary heart disease and angiographically proven coronary artery disease. The cholesterol, triglyceride, high-density lipoprotein, apoprotein B, and apoprotein A-I levels were compared by linear correlation to semiquantitative angiographic measures of coronary artery disease severity (coronary stenosis score and mean coronary stenosis score), the extent of mural involvement (coronary atheromatous score and mean coronary atheromatous score), and also the number of normal coronary artery segments, an alternative severity score (Jenkins), and left ventricular function score. Age, past and present cholesterol, low-density lipoprotein cholesterol, and apoprotein B levels correlated directly with the extent of disease (r = 0.27, 0.46, 0.29, 0.26, 0.35, respectively, P < 0.05 with coronary atheromatous score; r = 0.29, 0.44, 0.33, 0.30, 0.35, respectively, P < 0.05 with mean coronary atheromatous score). Age and New York Heart Association angina functional class correlated directly with disease severity (r = 0.25, 0.31, respectively, P < 0.05 with coronary stenosis score; r = 0.25, 0.34, respectively, P < 0.05 with mean coronary stenosis score). There was an inverse association between age, past and present cholesterol, low-density lipoprotein cholesterol, and apoprotein B levels with the number of normal segments (r = -0.23, -0.46, -0.38, -0.35, -0.39, respectively, P < 0.05). Multiple regression analysis was undertaken with lipoproteins and age as independent variables and angiographic scores as dependent variables; the apoprotein B level was the most predictive of the extent of coronary artery disease (P < 0.02) and inversely predicted the number of normal segments (P < 0.002). Of those variables entered into the regression model, only age was independently predictive of the severity of angiographic coronary artery disease. Apoprotein B levels are not predictive of coronary artery disease severity but do predict independently the extent of involvement of coronary atherosclerosis defined angiographically.


Abnormal Tilt Perception During Centrifugation in Patients with Vestibular Migraine.
Vestibular migraine (VM), defined as vestibular symptoms caused by migraine mechanisms, is very common but poorly understood. Because dizziness is often provoked in VM patients when the semicircular canals and otolith organs are stimulated concurrently (e.g., tilting the head relative to gravity), we measured tilt perception and eye movements in patients with VM and in migraine and normal control subjects during fixed-radius centrifugation, a paradigm that simultaneously modulates afferent signals from the semicircular canals and otoliths organs. Twenty-four patients (8 in each category) were tested with a motion paradigm that generated an inter-aural centrifugal force of 0.36 G, resulting in a 20° tilt of the gravito-inertial force in the roll plane. We found that percepts of roll tilt developed slower in VM patients than in the two control groups, but that eye movement responses, including the shift in the eye's rotational axis, were equivalent in all three groups. These results demonstrate a change in vestibular perception in VM that is unaccompanied by changes in vestibular-mediated eye movements and suggest that either the brain's integration of canal and otolith signals or the dynamics of otolith responses are aberrant in patients with VM.


Interlay Type-1 Tympanoplasty with or Without Cortical Mastoidectomy in an Inactive Mucosal Chronic Otitis Media with Large Central Perforation: A Retrospective Comparative Study.
Background: Chronic otitis media (COM) is a pathology involving the middle ear cleft characterized by discharging ear and a non-healing perforation in tympanic membrane. Different techniques have been used for closing the perforation but interlay myringoplasty has become popular among surgeons since the past few decades. Objectives: To evaluate and compare the success rate of Type-1 interlay tympanoplasty in large tympanic membrane perforation with or without cortical mastoidectomy in terms of graft take-up rate and improvement in hearing outcomes. Materials and methods: A retrospective study for the period of eighteen months with total of 90 patients further subdivided into two groups. Group I of 45 patients underwent Type-1 interlay tympanoplasty alone, and 45 patients in Group II underwent type-1 interlay tympanoplasty with cortical mastoidectomy. Results: In group I the mean pre-operative, post-operative pure tone average and air bone gap was found to be 36.49 ± 4.49, 29.24 ± 4.39 and 25.11 ± 3.15, 14.76 ± 3.12 respectively. In group II the mean pre-operative, post-operative pure tone average and air bone gap was found to be 35.60 ± 5.27, 25.96 ± 5.29 and 23.96 ± 3.76 and 13.33 ± 3.38. An independent sample t-test was performed for intergroup comparison and found to be statistically significant (p < 0.005). The graft uptake was 95.5% in group II and 82.2% in group I. Conclusion: Interlay type-1 tympanoplasty coupled with cortical mastoidectomy gives excellent results in terms air bone gap closure and graft uptake in inactive mucosal COM than Interlay type-1 tympanoplasty alone. The online version contains supplementary material available at 10.1007/s12070-023-03781-7.


Additional K-ras mutation analysis and Plectin-1 staining improve the diagnostic accuracy of pancreatic solid mass in EUS-guided fine needle aspiration.
One of the major genetic alterations in pancreatic ductal adenocarcinoma (PDAC) is the point mutation of K-ras gene. Plectin-1 was also recently identified as PDAC specific biomarker. The aim of this study was to investigate the improvement of diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) by using additional K-ras mutation analysis and Plectin-1 staining in patients with pancreatic mass. A total of 85 study patients with pancreatic mass underwent EUS-FNA and the final diagnoses were as follows; PDACs: 70 patients, pancreas neuroendocrine tumor: 4, metastasis to pancreas: 5, autoimmune pancreatitis: 3, chronic pancreatitis: 1, tuberculous lymphadenitis: 1, pseudocyst: 1. Sensitivity, specificity and accuracy of pathologic diagnosis in EUS-FNA specimen were 81%, 80% and 79% accordingly. When we combine K-ras gene mutation analysis with histological assessment, we could get the following results for sensitivity, specificity and accuracy; cytology and K-ras mutation analysis: 93%, 87%, and 92%, cytology, K-ras mutation analysis, and Plectin-1 staining: 96%, 93%, and 95%. Triple combinations of the techniques; cytology, K-ras gene mutation analysis, Plectin-1 staining could increase accuracy in diagnosis of PDACs. Further investigation of using minimal specimens from EUS-FNA may give us insight to understand the biological behavior of PDAC.


Why do we eat? Children's and adults' understanding of why we eat different meals.
In this study the author examined why children and adults think they need to eat. Preschoolers through adults were provided with physiological, social, psychological, and routine causes for eating breakfast, lunch, snack, and dinner, and were asked to either agree or disagree with the causal responses provided. A 4 Reason x 4 Meal repeated measures analysis of variance revealed significant main effects for meals and reasons, as well as significant Meal x Reason and Meal x Reason x Grade interactions. The effect sizes ranged from 0.1 to 0.7. Across all age groups, participants acknowledged physiological needs and desires (fulfilling hunger and needs to stay healthy) and routine (e.g., it is dinner time) as the primary causes for eating breakfast, lunch, and dinner. However, for snack physiological needs were the primary reason. Second-grade students onward spontaneously produced biological justifications such as the need for energy and nutrition as important reasons for food consumption. These results lend support to the developmental model that children's and adults' understanding of eating changes in middle childhood.


[Intraoperative 3D C-arm imaging. State of the art].
Mobile C-arms with the option of 3D imaging like the Iso-C(3D) allow for intraoperative 3D visualization of anatomical areas with complex three-dimensional structures like articular surfaces. In an 8-year period we performed 1,841 intraoperative control scans following osteosynthesis. Among these patients we registered the number of intraoperative adjustments of fracture reduction and implant position in correlation to the area of surgery. The majority of intraoperative examinations in 1,841 patients was performed in fractures of the calcaneus (20.5%) and the upper ankle joint (13.2%). Altogether we improved the reduction or the implant position intraoperatively in 21.5%. The majority of intraoperative revisions was seen in osteosynthesis of the calcaneus (40.3%), the upper ankle joint (30.9%) and fractures of the distal tibia (29%). The rate of revisions over the time was very stable. Intraoperative need for revision of reduction or implant position is not a rare phenomenon in our experience. Intraoperative 3D imaging is a valid tool to recognize and adjust suboptimal reduction or implant positioning. Intraoperative 3D imaging can improve the quality of osteosynthesis especially in fractures of joints and complex anatomical areas.


Studies in hemolysis in glucose-6-phosphate dehydrogenase-deficient African American neonates.
The role of hemolysis in the mechanism and prediction of hyperbilirubinemia was contrasted between glucose-6-phosphate dehydrogenase (G-6-PD)-deficient and -normal African American neonates. Corrected end tidal carbon monoxide (ETCOc) values from the subset of male neonates born to non-smoking African American mothers, drawn from a previously published study, were analyzed. The relationship between ETCOc and bilirubin values, the latter represented as percentiles on the hour of life specific bilirubin nomogram, was determined. Hyperbilirubinemia was defined as any bilirubin value > or =95th percentile for hour of life. 18.6% of 59 G-6-PD-deficient neonates developed hyperbilirubinemia, compared with 7.5% of 362 controls (relative risk 2.50, 95% confidence interval 1.31 to 4.76). As reported, ETCOc values (median, interquartile range) were significantly higher among G-6-PD-deficient neonates than controls (2.4 [2.0-2.9] vs. 2.1 [1.7-2.5] ppm, p<0.001. However, higher ETCOc values were limited to those G-6-PD-deficient neonates with lower bilirubin percentiles: among those whose bilirubin value did not exceed the 95th percentile ETCOc was 2.30 [2.00-2.85] vs. 2.00 [1.70-2.40] ppm in controls, p=0.001. In contrast, among the hyperbilirubinemic neonates ETCOc values were similar between G-6-PD-deficient neonates and controls: 2.7 [2.03-3.33] vs. 2.6 [2.33-3.45] ppm, p=0.9. In the G-6-PD-deficient neonates ETCOc > or =75th percentile contributed no additional predictive value for hyperbilirubinemia (likelihood ratio 1.8). G-6-PD-deficient African American neonates have increased hemolysis and increased rate of hyperbilirubinemia, but the hemolysis is neither a predominant factor in the pathogenesis of hyperbilirubinemia nor is it predictive of hyperbilirubinemia, over and above the already increased risk conferred by G-6-PD deficiency.


Current issues and problems in dealing with anaerobes in the clinical laboratory.
Because of the current concern for health care reform and the demands placed in the clinical microbiology laboratory by decreased resources, questions regarding appropriate work-up of anaerobes remains unresolved. Although anaerobes are ubiquitous, the number of anaerobes causing disease is relatively few. This article focuses on the need for isolation and identification of these anaerobes and emphasizes proper collection, culture, and identification techniques. Varying levels of expertise in isolation and identification of anaerobes are proposed, and the role of "rapid" identification kits in identification of these organisms is discussed.


Commentary: eight ways to prevent cancer: a framework for effective prevention messages for the public.
Research over the past 40 years has convincingly shown that lifestyle factors play a huge role in cancer incidence and mortality. The public, though, can often discount the preventability of cancer. That health information on the Internet is a vast and often scientifically suspect commodity makes promoting important and sound cancer prevention messages to the public even more difficult. To help address these issues and improve the public's knowledge of, and attitudes toward, cancer prevention, there need to be concerted efforts to create evidence-based, user-friendly information about behaviors that could greatly reduce overall cancer risk. Toward this end, we condensed the current scientific evidence on the topic into eight key behaviors. While not an end in themselves, "Eight Ways to Stay Healthy and Prevent Cancer" forms an evidence-based and targeted framework that supports broader cancer prevention efforts.


Antimicrobial susceptibilities, serogroups, and molecular characterization of avian pathogenic Escherichia coli isolates in Japan.
In total, 83 avian pathogenic Escherichia coli (APEC) isolates from avian colibacillosis during a period from 2001 to 2006 in Japan were investigated for serogroups, typical virulence factors, antimicrobial susceptibility, and genetic relatedness. The most common serogroup was O78 (30.1%); 80.7% of isolates harbored the iss gene and 55.4% of isolates harbored the tsh gene. Antimicrobial resistance of the isolates was found for ampicillin (77.1%), oxytetracycline (75.9%), kanamycin (36.1%), fradiomycin (33.7%), trimethoprim (25.3%), enrofloxacin (21.7%), and florfenicol (6.0%). Although multiple antimicrobial-resistant phenotypes (three or more antimicrobials) accounted for 54.2% of isolates, no isolate exhibited resistance to all agents tested. The fluoroquinolone-resistant isolates had point mutations in GyrA (Ser83 --> Leu, Asp87 --> Asn) and ParC (Ser80 --> Ile, Glu84 --> Gly). Of 18 enrofloxacin-resistant E. coli isolates, nine isolates belonged to serotype O78. In PFGE analysis, eight of the nine enrofloxacin-resistant O78 isolates were classified into an identical cluster. This suggests that a specific genotype of fluoroquinolone-resistant O78 APEC may be widely distributed in Japan.


[Biomechanical properties of skin during tissue expansion for breast-reconstructive surgery].
Mammary reconstruction following mastectomy involves breast augmentation, which probably sets the skin under tension. This aspect of mechanobiology has rarely been explored in an objective way. The aim of the present study was to measure the biomechanical properties of skin using a suction method. Eight sites of the thorax were assessed in 26 cases of mastectomy performed in 20 women aged 49+/-7 years. In order to distinguish the effects of breast augmentation from forces exerted by earth gravitation, measurements were performed in standing and lying down positions, both before and after breast augmentation of about 450 ml.


Visual Field Prediction: Evaluating the Clinical Relevance of Deep Learning Models.
Two novel deep learning methods using a convolutional neural network (CNN) and a recurrent neural network (RNN) have recently been developed to forecast future visual fields (VFs). Although the original evaluations of these models focused on overall accuracy, it was not assessed whether they can accurately identify patients with progressive glaucomatous vision loss to aid clinicians in preventing further decline. We evaluated these 2 prediction models for potential biases in overestimating or underestimating VF changes over time. Retrospective observational cohort study. All available and reliable Swedish Interactive Thresholding Algorithm Standard 24-2 VFs from Massachusetts Eye and Ear Glaucoma Service collected between 1999 and 2020 were extracted. Because of the methods' respective needs, the CNN data set included 54 373 samples from 7472 patients, and the RNN data set included 24 430 samples from 1809 patients. The CNN and RNN methods were reimplemented. A fivefold cross-validation procedure was performed on each model, and pointwise mean absolute error (PMAE) was used to measure prediction accuracy. Test data were stratified into categories based on the severity of VF progression to investigate the models' performances on predicting worsening cases. The models were additionally compared with a no-change model that uses the baseline VF (for the CNN) and the last-observed VF (for the RNN) for its prediction. PMAE in predictions. The overall PMAE 95% confidence intervals were 2.21 to 2.24 decibels (dB) for the CNN and 2.56 to 2.61 dB for the RNN, which were close to the original studies' reported values. However, both models exhibited large errors in identifying patients with worsening VFs and often failed to outperform the no-change model. Pointwise mean absolute error values were higher in patients with greater changes in mean sensitivity (for the CNN) and mean total deviation (for the RNN) between baseline and follow-up VFs. Although our evaluation confirms the low overall PMAEs reported in the original studies, our findings also reveal that both models severely underpredict worsening of VF loss. Because the accurate detection and projection of glaucomatous VF decline is crucial in ophthalmic clinical practice, we recommend that this consideration is explicitly taken into account when developing and evaluating future deep learning models.


Verification of Accuracy of CyberKnife Tumor-tracking Radiation Therapy Using Patient-specific Lung Phantoms.
To investigate the accuracy of the CyberKnife Xsight Lung Tracking System (XLTS) compared with that of a fiducial-based target tracking system (FTTS) using patient-specific lung phantoms. Three-dimensional printing technology was used to make individualized lung phantoms that closely mimicked the lung anatomy of actual patients. Based on planning computed tomographic data from 6 lung cancer patients who underwent stereotactic ablative radiation therapy using the CyberKnife, the volume above a certain Hounsfield unit (HU) was assigned as the structure to be filled uniformly with polylactic acid material by a 3-dimensional printer (3D Edison, Lokit, Korea). We evaluated the discrepancies between the measured and modeled target positions, representing the total tracking error, using 3 log files that were generated during each treatment for both the FTTS and the XLTS. We also analyzed the γ index between the film dose measured under the FTTS and XLTS. The overall mean values and standard deviations of total tracking errors for the FTTS were 0.36 ± 0.39 mm, 0.15 ± 0.64 mm, and 0.15 ± 0.62 mm for the craniocaudal (CC), left-right (LR), and anteroposterior (AP) components, respectively. Those for the XLTS were 0.38 ± 0.54 mm, 0.13 ± 0.18 mm, and 0.14 ± 0.37 mm for the CC, LR, and AP components, respectively. The average of γ passing rates was 100% for the criteria of 3%, 3 mm; 99.6% for the criteria of 2%, 2 mm; and 86.8% for the criteria of 1%, 1 mm. The XLTS has segmentation accuracy comparable with that of the FTTS and small total tracking errors.


Malignant pleurisy and intrathoracic dissemination in carcinoma of the lung: diagnostic, therapeutic and prognostic implications.
Of T4 disease of lung cancer, malignant pleurisy and intrathoracic dissemination are the greatest factor preventing a cure, despite the best efforts of surgery and various adjuvant therapy modalities. Preoperative evaluation of this disease is of first importance using conventional radiology and computed tomography. Of the 43 patients who were intraoperatively diagnosed to be the disease, 8 (18%) appeared on the conventional radiology as small amounts of pleural effusion, and 9 (21%) with a interlobar pleural thickening. Based on CT findings, 16 (67%) had one or more of some disseminated nodules, interlobar pleural thickening and broad pleural indentation. In patients with T4 disease, the 5-year survival rate was 14% in patients with malignant pleurisy and/or intrathoracic dissemination, compared with the 18% in those with direct invasion to great vessels, with no significant difference. According to intrapleural instillation as postoperative adjuvant therapy, the 5-year survival rate was 25% in the patients given interleukin-2, compared with 38 months of survival time for patients prescribed doxorubicin and 33 months for those underwent exploratory thoracotomy. A more favorable prognosis of patients whose malignant pleurisy and/or intrathoracic dissemination are first found at thoracotomy can be expected when postoperative intrapleural instillation of interleukin-2 is prescribed following the resection of the intrathoracic tumors.


Brain metastasis localized to an area of infarction.
A patient with adenosquamous carcinoma of the cervix developed brain metastases limited to an area of evolving infarction. This preferential localization of tumor in an area of previous tissue injury with neovascularization provides support, in the human, for the importance of local vascular factors in the development of brain metastases.


Corneal confocal microscopy reveals small nerve fibre loss correlating with motor function in adult spinal muscular atrophy.
5q Spinal muscular atrophy (SMA) is a progressive, inherited, and severely disabling - yet treatable - motor neuron disease. Although treatment options have evolved in recent years, biomarkers for treatment monitoring and prognosis prediction remain elusive. Here, we investigated the utility of corneal confocal microscopy (CCM), a non-invasive imaging technique to quantify small corneal nerve fibres in vivo, as a diagnostic tool in adult SMA. In this cross-sectional study, 19 patients with SMA type 3 and 19 healthy controls underwent CCM to measure corneal nerve fibre density (CNFD), corneal nerve fibre length (CNFL), and corneal nerve branch density (CNBD), as well as corneal immune cell infiltration. Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM) scores and a 6-Minute Walk Test (6MWT) were conducted to explore any correlation between CCM findings and motor function. Corneal nerve fibre parameters were decreased in SMA patients versus healthy controls (CNFD: p = 0.030; CNFL: p = 0.013; CNBD: p = 0.020) in the absence of relevant immune cell infiltration. CNFD and CNFL correlated with HFMSE scores (CNFD: r = 0.492, p = 0.038; CNFL: r = 0.484, p = 0.042) and distance covered in the 6MWT (CNFD: r = 0.502, p = 0.042; CNFL: r = 0.553, p = 0.023). Corneal confocal microscopy CCM reveals sensory neurodegeneration in SMA, thereby supporting a multisystem view of the disorder. Subclinical small nerve fibre damage correlated with motor function. Thus, CCM may be ideally suited for treatment monitoring and prognosis.


Determination of Poly (ADP-ribose) polymerase (PARP) homologues in human ejaculated sperm and its correlation with sperm maturation.
To investigate the presence of Poly (ADP-ribose) polymerase (PARP) and evaluate its function in ejaculated spermatozoa. Experimental study. Reproductive Research Center. Semen specimens from 18 healthy donors and 12 infertile males. Ejaculated spermatozoa were subjected to sperm fractionation with a double-layer density gradient, protein extraction, detection, immunoblotting, and mass spectrometry. Semen samples were exposed to PARP inducer staurosporine, or hydrogen peroxide with or without PARP inhibitor 3-aminobenzimide. Annexin V assay was examined for apoptosis by flow cytometry. We detected approximately 75 kDa, approximately 63 kDa, and approximately 60 kDa PARP homologues on the immunoblot of mature and immature sperm fraction isolated from human ejaculate, which were identified as PARP-1 ( approximately 75 kDa), PARP-9 ( approximately 63 kDa), and PARP-2 ( approximately 60 kDa), respectively. Western blot analysis showed a positive correlation between the amount of PARP protein and sperm maturity. PARP proteins (75 kDa, 63 kDa, and 60 kDa) were evaluated after inducing apoptosis by hydrogen peroxide and staurosporine exposure. PARP-2 may have a role in prevention of oxygen species/oxidative stress and chemical (staurosporine)-induced sperm cell apoptosis. The presence of the PARP homologue, that is, PARP-1 ( approximately 75 kDa), suggests its role in preventing damage of mature sperm. Additional studies are needed to delineate the role of PARP-9 in sperm physiology. The results from our study indicate an active role for PARPs in sperm cell physiology in preventing apoptosis.


A family of pyrazinone natural products from a conserved nonribosomal peptide synthetase in Staphylococcus aureus.
Each year in the United States, infections by methicillin-resistant Staphylococcus aureus (MRSA) are responsible for ∼19,000 deaths and result in $3-$4 billion of health care costs. Because skin colonization is a major risk factor for S. aureus infection, identifying novel small molecules produced by S. aureus can lead to new molecular insights into its ability to colonize and infect the host and new targets for antibacterial intervention. Here, we report that a nonribosomal peptide synthetase conserved across S. aureus and other skin-associated staphylococci encodes a family of three pyrazinone natural products. These molecules likely result from the synthesis and release of a dipeptide aldehyde, its spontaneous cyclization to a dihydropyrazinone, and subsequent oxidation to a pyrazinone. As an unexpected family of small molecule natural products from the pathogen S. aureus, the pyrazinones may open a new window into the interspecies interactions that underlie the poorly understood process of skin colonization.


Videodensitometric ejection fraction from intravenous digital subtraction right ventriculograms: correlation with first pass radionuclide ejection fraction.
Thirty-one consecutive patients undergoing intravenous blurred mask digital subtraction right ventriculography were submitted to first pass radionuclide angiography. Second order mask resubtraction of end-diastolic and end-systolic right ventricular digital image frames was executed using preinjection end-diastolic and end-systolic frames to rid the digital subtraction images of mis-registration artifact. End-diastolic and end-systolic perimeters were drawn manually by two independent observers with a light pen. Ejection fractions calculated from the integrated videodensitometric counts within these perimeters correlated well with those derived from the first pass radionuclide right ventriculogram (r = 0.84) and the interobserver correlation was acceptable (r = 0.91). Interobserver differences occurred more frequently in patients with atrial fibrillation and in those whose tricuspid valve planes were difficult to discern on the digital subtraction right ventriculograms. These results suggest that videodensitometric analysis of digital subtraction right ventriculograms is an accurate method of determining right ventricular ejection fraction and may find wide clinical applicability.


Variation in leaf trichomes and nutrients of Wigandia urens (Hydrophyllaceae) and its implications for herbivory.
Leaf trichome variation was studied in a population of Wigandia urens (Hydrophyllaceae) in relation to water availability, diversity of herbivorous insects, and grazing rates. Plants of W. urens have glandular and urticant (stinging hairs) trichomes, and it is possible to distinguish two types of leaves: "smooth" leaves with only glandular trichomes and "bristly" leaves with both types of trichomes. Density of urticant trichomes was negatively correlated with weekly mean precipitation. Fourteen species of insects in five different orders feed on leaves of W. urens throughout the year. Grazing rates varied according to type and age of leaves. Grazing rates were lower in smooth than bristly young leaves but the rates were similar for mature leaves. Secondary metabolites, screened using qualitative methods, showed similar classes of compounds in both types of leaves. Bristly leaves had significantly higher concentrations of nitrogen, phosphorous and water and these nutritional differences were well correlated with the differences in grazing rates between bristly and smooth leaves.


Ecstasy (3, 4-methylenedioxymethamphetamine) use among Japanese rave population.
The aim of this study was to examine the prevalence of 3, 4-methylenedioxymethamphetamine (MDMA) use and to identify characteristics of MDMA users among rave attendees in Japan. This is the first rave-population study focusing on MDMA use in Japan. The anonymous self-administrative questionnaire was conducted using laptop computers at four rave parties at three different venues in Tokyo, Japan. Participants were asked about lifetime use of MDMA and other club drug use, characteristics of rave attendance, and their demographics. Questionnaires were completed by 300 rave attendees (47.3% female), 68.3% of whom were aged 20-29 years, and 92.3% of whom had completed high school. Among the participants, 8.0% reported MDMA use. Compared with 'non-drug controls' (the participants who had never used any illicit drugs), MDMA users were significantly more likely to be 30-39-year-old men. In addition, compared with 'cannabis users' (non-MDMA users who had used cannabis), MDMA users were significantly more likely to use other drugs and reported more adverse health effects due to 'polydrug use'. Furthermore, MDMA users were significantly more likely to go to raves and preferred smaller venues. Our results clearly suggest that rave attendees have a higher lifetime prevalence of MDMA use than the Japanese general population (0.2% reported in 2007). MDMA users are deeply involved in rave parties, and MDMA use may have high potential to generate close relationships among rave attendees. Therefore, MDMA users may have more opportunities to access MDMA than cannabis users and non-drug controls.


Glioblastoma: Radiation treatment margins, how small is large enough?
Standard treatment for glioblastoma consists of surgical resection followed by radiation therapy with concurrent and adjuvant chemotherapy. Conventional radiation clinical treatment volumes include a 2- to 3-cm margin around magnetic resonance imaging or computed tomography enhancing abnormalities in the brain as well as a margin around the T2 or fluid-attenuated inversion recovery abnormality. However, there remains significant variability with respect to whether such extensive margins are necessary. Collectively, we as authors of this manuscript also use different margins, with A.G.W. employing European Organization for Research and Treatment of Cancer recommendations of a 2- to 3-cm margin on T1 enhancement for 60 Gy and M.P.M. using Radiation Therapy Oncology Group recommendations of 2 cm on T2 signal abnormality for the initial 46 Gy and 2.5-cm margin on T1 enhancement for a 14-Gy boost. Our experiences reflect the heterogeneity of margin definition and selection for this disease and underscore an important area of further research to minimize this variability. In this article, we review studies exploring recurrence patterns and outcomes in patients treated using both conventional and more limited margins. We conclude that treating to "smaller" margins does not alter recurrence patterns nor does it result in inferior survival, but whether this is because of the inherently limited benefit of radiation therapy in the first place, or whether it is truly because microscopic tumor control at larger distances is not an issue, remains unestablished.


The clinical relevance of biomechanics.
Most neurologists are familiar with biomechanics but may be unsure of the relevance of this field to their practice. Actually those involved in musculoskeletal problems are undoubtedly using biomechanical principles. This article is limited to the spine, but the basic principles of biomechanics are applicable to other parts of the body. In this article, we describe the spine and trunk as a biomechanical organ, the biomechanical principles behind back injuries and their importance, the role of biomechanical issues in pain, the utility of clinical tests based on biomechanical principles, the effects of aging, and the future directions in spine biomechanical research.


Histochemical basis of the vertebrate epidermis differentiation in the comparative aspects.
The study of epiderm in the adult form of amphibians reptiles mammals, including man, has shown that in amphibians histochemical epiderm differentiation finishes in the accumulation of protein containing high concentrations of sulhydryl and cationic groups in the protective zone. The reptiles are characterized by the new type of histochemical differentiation of epiderm, the protective zone of which accumulates the proteins, rich in disulphide groups of cystine. Cationic protein and protein, containing sulfhydryl groups, are shifted into the transitional zone. Such zone was not detected in the amphibians epiderm. In the mammals the epiderm of the segment, covered with hair, contains high concentrations of cystine and cationic groups in the protective zone, and the transitional zone accumulates the proteins with high content of histidine and arginine amino-acid residues. In the similar types of epidermal segments of man the protective zone does not contain free cationic protein. Hairless epiderm segments of the studied mammals and man are differentiated in the similar way.


Characterization of different viruses infecting the marine harmful algal bloom species Phaeocystis globosa.
Twelve lytic viruses (PgV) infecting the marine unicellular eukaryotic harmful algal bloom species Phaeocystis globosa were isolated from the southern North Sea in 2000-2001 and partially characterized. All PgV isolates shared common phenotypic features with other algal viruses belonging to the family Phycodnaviridae and could be categorized in four different groups. Two main groups (PgV Group I and II) were discriminated based on particle size (150 and 100 nm respectively), genome size (466 and 177 kb) and structural protein composition. The lytic cycle showed a latent period of 10 h for PgV Group I and latent periods of 12 h and 16 h for PgV Group IIA and IIB. Host specificity and temperature sensitivity finally defined a fourth group (PgV Group IIC). Our results imply that viral infection plays an important role not only in P. globosa dynamics but also in the diversity of both host and virus community.


A simple guide for completing an integrative review using an example article.
The integrative review (IR) is a methodology of importance to nursing and other disciplines to evaluate and synthesize data from diverse sources to answer research questions, generate new theories, and to provide a comprehensive view of what is known regarding a topic of interest. Current, concise and introductory articles on how to conduct IRs are limited. Although a bias may exist that the IR is less rigorous than other types of literature reviews, the complexity of the search and evaluation of diverse sources increases the need for rigor to produce a well-written IR that advances evidence-based practice (EBP). This article provides a guide for students and beginning researchers to conduct this type of review by summarizing the IR into simple steps with strategies to increase rigor at each step. Use of an example IR related to acupuncture for neuropathy illustrates key points and lessons learned during the process.


Tackling global health security by building an academic community for One Health action.
One Health approach is crucial to tackling complex global public health threats at the interface of humans, animals, and the environment. As outlined in the One Health Joint Plan of Action, the international One Health community includes stakeholders from different sectors. Supported by the Bill & Melinda Gates Foundation, an academic community for One Health action has been proposed with the aim of promoting the understanding and real-world implementation of One Health approach and contribution towards the Sustainable Development Goals for a healthy planet. The proposed academic community would contribute to generating high-quality scientific evidence, distilling local experiences as well as fostering an interconnected One Health culture and mindset, among various stakeholders on different levels and in all sectors. The major scope of the community covers One Health governance, zoonotic diseases, food security, antimicrobial resistance, and climate change along with the research agenda to be developed. The academic community will be supported by two committees, including a strategic consultancy committee and a scientific steering committee, composed of influential scientists selected from the One Health information database. A workplan containing activities under six objectives is proposed to provide research support, strengthen local capacity, and enhance global participation. The proposed academic community for One Health action is a crucial step towards enhancing communication, coordination, collaboration, and capacity building for the implementation of One Health. By bringing eminent global experts together, the academic community possesses the potential to generate scientific evidence and provide advice to local governments and international organizations, enabling the pursuit of common goals, collaborative policies, and solutions to misaligned interests.


East‒West genetic differentiation across the Indo-Burma hotspot: evidence from two closely related dioecious figs.
Understanding biodiversity patterns and their underlying mechanisms is of interest to ecologists, biogeographers and conservationists and is critically important for conservation efforts. The Indo-Burma hotspot features high species diversity and endemism, yet it also faces significant threats and biodiversity losses; however, few studies have explored the genetic structure and underlying mechanisms of Indo-Burmese species. Here, we conducted a comparative phylogeographic analysis of two closely related dioecious Ficus species, F. hispida and F. heterostyla, based on wide and intensive population sampling across Indo-Burma ranges, using chloroplast (psbA-trnH, trnS-trnG) and nuclear microsatellite (nSSR) markers, as well as ecological niche modeling. The results indicated large numbers of population-specific cpDNA haplotypes and nSSR alleles in the two species. F. hispida showed slightly higher chloroplast diversity but lower nuclear diversity than F. heterostyla. Low-altitude mountainous areas of northern Indo-Burma were revealed to have high genetic diversity and high habitat suitability, suggesting potential climate refugia and conservation priority areas. Strong phylogeographic structure and a marked east‒west differentiation pattern were observed in both species, due to the interactions between biotic and abiotic factors. Interspecific dissimilarities at fine-scale genetic structure and asynchronized historical dynamics of east‒west differentiation between species were also detected, which were attributed to different species-specific traits. We confirm hypothesized predictions that interactions between biotic and abiotic factors largely determine the patterns of genetic diversity and phylogeographic structure of Indo-Burmese plants. The east‒west genetic differentiation pattern observed in two targeted figs can be generalized to some other Indo-Burmese plants. The results and findings of this work will contribute to the conservation of Indo-Burmese biodiversity and facilitate targeted conservation efforts for different species.


Pulmonary cysticercosis: A case report of abnormal lung nodule based on chest computerized tomography.
Pulmonary cysticercosis is one of the rare complications of cysticercosis that occurs worldwide, especially in developing countries. Its clinical presentation can range from asymptomatic, pleural effusion, and constitutional symptoms to incidental pulmonary nodule. Here, we report pulmonary cysticercosis detected as a pulmonary nodule in computed tomography. Positron emission tomography revealed that the nodule was non-FDG avidity. However, the slow-growing pattern of the nodule raised a concern to the clinician to achieve definite diagnosis by surgical biopsy. Histopathological examination revealed cysticercosis. The patient was treated with praziquantel.


Endoscopic diode laser therapy for gastric hyperplastic polyps in cirrhotic patients.
Purpose Endoscopic polypectomy to remove gastric hyperplastic polyps in cirrhotic patients is associated to a high risk of postprocedural bleeding. The current study set out to examine the effect of diode laser therapy used to treat this type of polyps in cirrhotic patients. Methods This single-center study retrospectively examined the data of cirrhotic patients with macroscopic bleeding or anemia who underwent diode laser therapy (940 nm wave length, 30-W power setting in continuous mode) to remove histology-confirmed hyperplastic gastric polyps. Results A total of 222 polyps (mean diameter 10 ± 8 mm) were treated in 55 patients who were included in the study. No complications such as bleeding or perforations were reported. After a mean of 5 ± 4 sessions, 31 patients (56%) were completely healed. In 16 patients (29%), there was only a partial response (mean polyp reduction diameter of 64 ± 15%), while 8 (15%) patients did not respond to treatment. Statistically significant better results were noted in the patients who underwent ≥ 2 laser sessions. Hemoglobin levels and number of blood transfusions required were not statistically different after treatment. After a mean study period of 21 ± 17 months, polyp recurrences were noted in 11 patients (20%), but none of the polyps had degenerated. Conclusion Diode laser therapy was found to be a safe treatment for hyperplastic polyps in cirrhotic patients. Due to the presence of others bleeding lesions in cirrhotic patients, this treatment did not have an impact on anemia and transfusion requirements.


Noninvasive ventilation with helium-oxygen in children.
Most existing literature on noninvasive ventilation (NIV) in combination with helium-oxygen (HELIOX) mixtures focuses on its use in adults, basically for treatment of acute exacerbations of chronic obstructive pulmonary disease. This article reviews and summarizes the theoretical basis, existing clinical evidence, and practical aspects of the use of NIV with HELIOX in children. There is only a small body of literature on HELIOX in pediatric NIV but with positive results. The reported experience focuses on treatment for patients with severe acute bronchiolitis who cannot be treated with standard therapies. The inert nature of helium adds no biological risk to NIV performance. Noninvasive ventilation with HELIOX is a promising therapeutic option for children with various respiratory pathologies who do not respond to conventional treatment. Further controlled studies should be warranted.


Insulin inhibits glucocorticoid-induced stimulation of liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene transcription.
6-Phosphofructo-2-kinase (PFK-2)/fructose-2,6-bisphosphatase (FBPase-2) catalyzes the synthesis and degradation of fructose 2,6-bisphosphate, a potent stimulator of glycolysis. Transcription of the mRNA encoding rat liver PFK-2/FBPase-2 is stimulated by insulin and by glucocorticoids in rat hepatoma cells. We show here that insulin can also prevent and reverse this glucocorticoid effect. The inhibitory effect of insulin is independent of extracellular glucose and does not require ongoing protein synthesis. We conclude that insulin exerts opposite effects on PFK-2/FBPase-2 gene transcription depending on the hormonal context.


An ischemic index from the electrocardiogram to select patients with low left ventricular ejection fraction for coronary artery bypass grafting.
Patients who have a decreased left ventricular (LV) ejection fraction (EF) may be denied coronary by-pass grafting (CABG) because it is assumed that improvement in function is unlikely. If the low LVEF were due to myocardial necrosis, this assumption would be valid. If the dysfunction were due to both necrosis and ischemia, however, then improvement may be possible with CABG. A method capable of identifying such patients would be useful. In this study, an "ischemic index" was determined for 37 patients based on the difference between the presurgical LVEF estimated from the standard 12-lead electrocardiogram by the Selvester QRS score (indicating the extent of dysfunction due to necrosis) and the presurgical LVEF measured from resting multigated radionuclide angiography (indicating dysfunction due to both necrosis and ischemia). It was hypothesized that a high ischemia index, that is, a large discrepancy between estimated and measured LVEF, would be associated with an improved post-surgical measured LVEF. The results showed that patients with an ischemic index of less than or equal to 0 had a mean decrease in LVEF of 8% (p = 0.02) and those with an index between 0 and 10 had no mean change. Patients with an index greater than or equal to 11, however, had a mean increase of 5% (p = 0.02), suggesting that depressed LVEF may improve following CABG among patients whose low function is due primarily to reversible ischemia as indicated by a high ischemic index.


Model improvement and future projection of permafrost processes in a global land surface model.
To date, the treatment of permafrost in global climate models has been simplified due to the prevailing uncertainties in the processes involving frozen ground. In this study, we improved the modeling of permafrost processes in a state-of-the-art climate model by taking into account some of the relevant physical properties of soil such as changes in the thermophysical properties due to soil freezing. As a result, the improved version of the global land surface model was able to reproduce a more realistic permafrost distribution at the southern limit of the permafrost area by increasing the freezing of soil moisture in winter. The improved modeling of permafrost processes also had a significant effect on future projections. Using the conventional formulation, the predicted cumulative reduction of the permafrost area by year 2100 was approximately 60% (40-80% range of uncertainty from a multi-model ensemble) in the RCP8.5 scenario, while with the improved formulation, the reduction was approximately 35% (20-50%). Our results indicate that the improved treatment of permafrost processes in global climate models is important to ensuring more reliable future projections.


Understanding low adherence to an exercise program for adolescents with obesity: the HEARTY trial.
Despite efforts to improve adherence to physical activity interventions in youth with obesity, low adherence and attrition remain areas of great concern. The study was designed to determine which physiological and/or psychological factors predicted low adherence in adolescents with obesity enrolled in a 6-month exercise intervention study aimed to improve body composition. Three hundred four adolescents with obesity aged 14-18 years who volunteered for the HEARTY (Healthy Eating Aerobic and Resistance Training in Youth) randomized controlled trial completed physiological (body mass index, waist circumference, per cent body fat, resting metabolic rate and aerobic fitness) and psychological (body image, mood, self-esteem and self-efficacy) measures. One hundred forty-one out of 228 (62%) randomized to exercise groups had low adherence (completed <70% of the prescribed four exercise sessions per week) to the intervention protocol. Logistic regression revealed that there were no baseline demographic or physiological variables that predicted low adherence in the participants. Appearance concern (a subscale of body image) (odds ratio [OR] 1.46, 95% confidence interval [CI]: 1.01, 2.1, P = 0.04), depressive mood (OR 1.12, 95% CI: 1.01, 1.23, P = 0.03) and confused mood (OR 1.16, 95% CI: 1.05, 1.27, P = 0.003) (two subscales of mood) were significant predictors of low adherence. Adolescents with obesity who had higher appearance concerns and depressive and confused moods were less likely to adhere to exercise. Body image and mood should be screened to identify adolescents who may be at high risk of poor adherence and who may need concurrent or treatment support to address these psychological issues to derive maximal health benefits from an exercise programme.


Molecular basis of the diversity of hepatitis B virus core-gene products.
All hepatitis B viruses examined to date code for at least two different core-gene products which are referred to as the c- and the e-protein. In the case of the human hepatitis B virus, they are known as the HBcAg and the HBeAg. Although these proteins share most of their primary amino acid sequence, they exhibit quite distinct properties. The e-protein is located in the cytoplasm and the nucleus of infected cells and very efficiently assembles into nucleocapsids. By contrast, the e-protein does not form particles. It enters the secretory pathway and is actively secreted by the cells. Here we describe the biosynthetic pathways by which the c- and e-proteins are expressed and summarize recent data from our laboratory showing that the antigenic and biophysical properties which distinguish the HBeAg from the HBcAg are primarily due to the 10 amino acid long portion of the HBeAg leader sequence that remains attached to the HBeAg after cleavage.