Independent walking and cognitive development in preschool children with Dravet syndrome.
To investigate the relation between cognitive and motor development in preschool aged children with Dravet syndrome, in particular between the age of independent walking and cognitive development. Results of cognitive and motor developmental assessments and the age of independent walking were retrieved retrospectively from the medical records of 33 children (17 males, 16 females; mean age at last evaluation 33.2mo, SD 8.2mo, range 9-48mo) diagnosed with Dravet syndrome. Cognitive and motor developmental age, derived from the Bayley Scales of Infant Development or through standardized neurodevelopmental assessment, were converted into cognitive and motor developmental quotients. Multiple test scores per child were included. A strong positive relation was found between cognitive and motor developmental quotient (Pearson r=0.854; p<0.001) in 20 children (slope=0.75; 95% CI: 0.54-0.95). A later age of independent walking was associated with a lower cognitive developmental quotient (28 children; p<0.001; slope=-1.01; 95% CI: -1.53 to -0.49). A higher cognitive developmental quotient was seen in children with an age at testing younger than 24 months. The cognitive developmental quotient of children with a delay in independent walking (>17.6mo) was significantly lower than those without a delay (p=0.006). A strong relation exists between cognitive and motor development. Furthermore, the age of independent walking might be an important indicator of the development of children with Dravet syndrome. Cognitive and motor development are strongly related in children with Dravet syndrome. Later age of independent walking is associated with worse cognitive development in children with Dravet syndrome.


Pharmacological aspects of gonadal alcohol and aldehyde-dehydrogenase.
1. A brief overview of gonadal alcohol dehydrogenase (ADH) and aldehyde-dehydrogenase (ALDH) is presented and their relationships to gonadal toxicity of ethanol has been discussed. 2. The distributions of ADH and ALDH among major reproductive tissues of rodents, their subcellular localization and kinetic properties were summarized. 3. The sensitivity of testicular ADH and ALDH to ethanol intake, various psychoactive agents and steroidal compounds was assessed and the implication of these enzymes in gonadal ethanol-drug interaction has been suggested. 4. The possible role of testicular ALDH in tumorigenesis and in high altitude endocrine sensitivity to ethanol has been addressed.


Anxiety trajectories: An observational study of women undergoing chemotherapy for breast or gynecological cancer.
While anxiety is prevalent among women who undergo chemotherapy for breast or gynecologic cancer, research on its predictors has focused primarily on cross-sectional evaluations or on assessments of anxiety prior to and after receipt of chemotherapy. Few studies have evaluated for predictors of inter-individual variability in levels of anxiety during chemotherapy. This study evaluated for inter-individual differences in anxiety across two cycles of chemotherapy and identified demographic, clinical, symptom, and psychological adjustment (e.g., stress, coping) characteristics associated with initial levels and trajectories of anxiety. Patients with breast (n = 530) or gynecologic (n = 233) cancer completed the Spielberger State Anxiety Inventory six times over two cycles of chemotherapy. At enrollment, self-report measures were used to assess demographic, symptom, stress, and coping characteristics. Hierarchical linear modeling was used to evaluate for risk factors associated with initial levels and trajectories of state anxiety. At enrollment, demographic, clinical, symptom, and psychological adjustment characteristics associated with inter-individual differences of anxiety were: marital status, functional status, sleep disturbance, cognitive function, global stress, cancer-specific stress, resilience, sense of coherence, and the coping strategies of venting and self-blame. Employment status and morning fatigue were the only characteristics associated with inter-individual differences in the trajectories of anxiety. Denial was the only characteristic associated with both initial levels and the trajectories of anxiety. A variety of patient characteristics predicted initial levels of anxiety. Fewer characteristics predicted trajectories of anxiety. Identification of specific risk factors, such as avoidant coping, suggests the need for targeted interventions among higher-risk patients.


Evaluating medication-related services in a hospital setting using the disconfirmation of expectations model of satisfaction.
Patient satisfaction is considered an important outcome measure of services and associated with behavioral intentions. The appraisal process commonly used in satisfaction models is the disconfirmation of expectations. A patient compares his or her experience to preexisting expectations. The resulting satisfaction from this comparison is dependent on whether the patient's expectations are superior, inferior, or just as expected. The aims of this study were to (1) determine the relationship between disconfirmation of expectations with medication-related services and patient satisfaction with medical care; and (2) determine if patient satisfaction is related to the likelihood to say good things about the medical care provided at the hospital to family and friends. A cross-sectional, nonexperimental study design was implemented to test the disconfirmation of expectations model. Patients on warfarin therapy and recently discharged from an acute care hospital to their homes were surveyed by mail. The survey asked about how well the hospital services related to medication therapy met patient expectations. Satisfaction with medical care and the likelihood of positive word of mouth regarding the medical care were also measured. Structural equation modeling (SEM) was used to test the model. The survey response rate was 34% (n=187). Factor analysis of the 7 disconfirmation of expectation items resulted in a 2-factor solution: (1) medication counseling and (2) discharge medication services. The SEM demonstrated that the model was significant; however, the disconfirmation of expectation items did not significantly relate to the 1-item satisfaction measure. Patient satisfaction and the behavioral intentions measures were significantly related. A post hoc analysis using SEM demonstrated that the disconfirmation of expectations factors did significantly relate to a higher-order latent construct. This construct also related to patient satisfaction. The disconfirmation of expectations has a role in a postservice experience response expressed by the patient, but not as a direct antecedent to patient satisfaction. Opportunities to improve the model are the use of a multi-item satisfaction measure and the inclusion of patient affect.


Protocol for rapid clearing and staining of fixed Arabidopsis ovules for improved imaging by confocal laser scanning microscopy.
A salient topic in developmental biology relates to the molecular and genetic mechanisms that underlie tissue morphogenesis. Modern quantitative approaches to this central question frequently involve digital cellular models of the organ or tissue under study. The ovules of the model species Arabidopsis thaliana have long been established as a model system for the study of organogenesis in plants. While ovule development in Arabidopsis can be followed by a variety of different imaging techniques, no experimental strategy presently exists that enables an easy and straightforward investigation of the morphology of internal tissues of the ovule with cellular resolution. We developed a protocol for rapid and robust confocal microscopy of fixed Arabidopsis ovules of all stages. The method combines clearing of fixed ovules in ClearSee solution with marking the cell outline using the cell wall stain SCRI Renaissance 2200 and the nuclei with the stain TO-PRO-3 iodide. We further improved the microscopy by employing a homogenous immersion system aimed at minimizing refractive index differences. The method allows complete inspection of the cellular architecture even deep within the ovule. Using the new protocol we were able to generate digital three-dimensional models of ovules of various stages. The protocol enables the quick and reproducible imaging of fixed Arabidopsis ovules of all developmental stages. From the imaging data three-dimensional digital ovule models with cellular resolution can be rapidly generated using image analysis software, for example MorphographX. Such digital models will provide the foundation for a future quantitative analysis of ovule morphogenesis in a model species.


The cigarette market in Brazil: new evidence on illicit practices from the 2019 National Health Survey.
To explore new evidence on illicit practices, such as selling legal brands below the minimum legal price (MLP), and smugglers selling illicit brands at or above the MLP. For the first time in Brazil, self-reported information on cigarette brand name and price paid per pack in smokers' last purchase from a nationally representative survey conducted in 2019 was used to distinguish the illicit and the legal markets. We estimated the proportion of illicit cigarette consumption, using the combination of brand and price. The proportion of smuggled illicit cigarette consumption based on brands not approved on the Brazilian market was estimated at 38.6% (95% CI: 35.8% to 41.5%). When we added legal brands not paying taxes, it increased to 47.1% (95% CI: 44.2% to 49.9%). Around 25% of illicit brand cigarettes were sold at or above MLP. In Brazil, since 2017 there is a lack of adjustment in tobacco taxes and the MLP for inflation and income growth. The increase in cigarette affordability and the presence on the market of a segment of 'higher-priced' illicit brands suggest patterns of illicit brand loyalty and/or perceived 'brand quality' among smokers of illicit cigarettes. The evidence also shows that a sizeable proportion of legal brand cigarettes were sold below the MLP. This study offers insight into what happened in circumstances in which a government failed to keep current with tax policies and the monitoring of domestic manufacturing. Brazil has been a world leader in the monitoring of the tobacco epidemic, and this study also offers an innovative use of data that an increasing number of countries are collecting.


Robotic Splenic Vessels Preserving Distal Pancreatectomy in a Post-Distal Gastrectomy Patient.
The optimal procedure during distal pancreatectomy (DP) for patients who have undergone distal gastrectomy (DG) remains unclear. Several papers on remnant gastric ischemia have reported that the preserved splenic vessels are essential for the proximal remnant stomach.1-4 We evaluated the outcomes of DP for post-DG patients in our hospital and introduced robotic splenic vessels preserving DP (R-SPDP). Postoperative short-term outcomes of DP for post-DG patients during 2014 and 2021 were evaluated. Next, R-SPDP was performed for a post-DG patient with the intention of preserving the remnant stomach safely. The double bipolar method was used to dissect the adhesions around the splenic vessels.5,6 The splenic artery was clamped at the root side to prevent bleeding.7 All short gastric arteries and veins, which were the main feeders of the remnant stomach, were preserved and resection was completed. After resection, the indocyanine green (ICG) fluorescence angiography confirmed blood flow in the short gastric arteries and veins and good return blood flow to the splenic vein.8 RESULTS: Of four patients (50.0%, of 8 DP patients) in whom the remnant stomach was preserved, one conventional DP case had poor ICG perfusion and presented with remnant stomach ischemia postoperatively. The R-SPDP case with good ICG perfusion had a total operation time of 371 minutes and intraoperative blood loss of 10 mL. The oral diet was started on postoperative Day 3, and the postoperative course was uneventful. R-SPDP can be a good option for post-DG patients to preserve the remnant stomach safely.


Mechanism of isoproterenol-induced angina pectoris in patients with obstructive hypertrophic cardiomyopathy and normal coronary arteries.
In 14 patients with obstructive hypertrophic cardiomyopathy and angiographically normal coronary arteries, 8 with angina (group B) and 6 without (group A), the effects of intravenous isoproterenol, 2 to 4 micrograms/min, followed by intravenous propranolol, 0.2 mg/kg, were studied. An intraventricular systolic gradient less than 50 mm Hg, high-quality echocardiograms and cineangiograms and high-fidelity pressure tracings were selection criteria. Hemodynamic and metabolic variables were assessed during basal conditions, after 5 minutes of isoproterenol infusion or at angina and ST-segment depression, and 5 and 10 minutes after intravenous propranolol infusion. Isoproterenol increased the intraventricular systolic gradient more significantly in group B than in group A (102.4 +/- 8.3 vs 52.2 +/- 8.2, p less than 0.0001). Group B also had higher left ventricular end-diastolic pressure (32.5 +/- 3.9 vs 20.2 +/- 5.7), lower mean arterial pressure (69.7 +/- 3.5 vs 84.7 +/- 4.8) and a smaller increase in coronary sinus flow (176.1 +/- 9.2 vs 261.5 +/- 33.9, all p less than 0.0001), concomitant with lactate release and ST-segment depression. Propranolol promptly reversed hemodynamic and metabolic changes caused by isoproterenol, except for a further coronary sinus flow increase (from 176.1 +/- 9.2 to 219 +/- 14.2 ml/min, p less than 0.001), and heart rate decrease below basal values (57.8 +/- 7.5 vs 79.9 +/- 9.8 beats/min, p less than 0.001) in group B.(ABSTRACT TRUNCATED AT 250 WORDS)


Mental health problems and school performance in first graders: results of the prospective cohort study ikidS.
We aimed to estimate unbiased effects of mental health problems (MHPs) on school performance in first graders, with an emphasis on rigorous adjustment for potential confounders. A population-based prospective cohort study was performed in the area of Mainz-Bingen (Germany). In 2015, all preschoolers were approached, and the presence and type of MHP (externalising/internalising) and other physical chronic health conditions were identified by the preschool health examination and study-specific questionnaires. At the end of the first grade, school performance (reading, writing, numeracy, and science) was assessed by the class teacher and rated on a four-item scale ranging from - 8 to + 8. Of 3683 children approached, 2003 (54%) were enrolled. School performance was available for 1462 children (51% boys, mean age 7.3 years). Of these, 41% had signs of at least one MHP. Compared to children without indications of mental and physical chronic health conditions, children with MHPs had lower school performance scores [adjusted mean difference - 0.98, 95% CI (- 1.35; - 0.61); P < 0.001]. Regarding the type of MHP, externalising MHPs were associated with poor school performance [adjusted mean difference - 1.44, 95% CI (- 1.83; - 1.05); P < 0.001], while internalising MHPs were not. Children with hyperactivity inattention problems were most affected [adjusted mean difference - 1.96, 95% CI (- 2.36; - 1.56); P < 0.001]. Externalising MHPs and in particular hyperactivity inattention problems may already affect school performance in early primary school. Identification of children with externalising MHPs prior to school entry may help to prevent impaired academic achievement in affected children.


Radiology-pathology conference at Robert Wood Johnson Medical School. Benign renal angiomyolipoma.
Angiomyolipoma is a benign tumor of the kidney. Conservative management of this tumor requires its differentiation from hypernephroma. This can be accomplished by identification of the fat within the tumor with CT scanning. The authors present a case report.


A comparison of the effect of lisinopril and hydrochlorothiazide on electrolyte balance in essential hypertension.
The effects of lisinopril 10-20 mg or hydrochlorothiazide 25-50 mg (each given once daily) on blood pressure, serum sodium, potassium and magnesium concentrations, total body potassium and urinary cation excretion were compared in a group of hypertensive patients using a double blind randomised crossover design. Each active treatment phase lasted six weeks and a total of sixteen patients completed the study. Both lisinopril and hydrochlorothiazide produced clinically significant decreases in blood pressure. However, lisinopril treatment produced a mean reduction of 14 mmHg in sitting diastolic pressure compared with a 7 mmHg reduction for hydrochlorothiazide treatment. This difference was statistically significant. The decrease in the concentration of serum potassium during hydrochlorothiazide treatment was greater than that during lisinopril treatment (0.53 vs 0.01 mmol.1). The absolute value of serum potassium was significantly lower on hydrochlorothiazide than on lisinopril therapy. Neither treatment had an effect on serum magnesium concentrations, nor was there any significant effect of either treatment on urine volume or urinary excretion of sodium, potassium or magnesium. There was a trend towards increased total body potassium concentration on lisinopril compared with a decrease in total body potassium on hydrochlorothiazide. However, this difference was just outside the range of statistical significance. Both treatments were equally well tolerated. The results indicate slight superiority of lisinopril over hydrochlorothiazide with regard to control of diastolic blood pressure with a better effect on overall electrolyte balance.


Association of lateral rectus muscle volume and ocular motility with the abducens nerve in Duane's retraction syndrome.
To investigate the relationship between ocular motility and lateral rectus (LR) muscle volume according to the presence or absence of the abducens nerve in patients with Duane's retraction syndrome (DRS) using high-resolution magnetic resonance imaging (MRI). A total of 54 unilateral DRS patients were divided into two groups according to high-resolution MRI findings: DRS without an abducens nerve on the affected side (absent CN6 group, n = 45) and DRS with symmetric abducens nerves on both sides (present CN6 group, n = 9). Ocular motility was measured by image analysis based on nine gaze photographs. LR volume was measured on T2-weighted coronal MRI of the orbit, and the ratio of paretic/normal side (P/N) LR volume was investigated. Association of the abducens nerve with various parameters including ocular motility, LR volume, and ratios of P/N LR volume were determined. LR volume was smaller in the affected eye than the non-affected eye in both groups. In the present CN6 group, abducens nerve diameter and the ratio of P/N LR volume showed a positive correlation. A smaller LR volume and more limitation of abduction in the affected eye were predictive of an absent abducens nerve in DRS. LR muscle hypoplasia was apparent in the affected eye of DRS patients. Abducens nerve diameter positively correlated with the ratio of P/N LR volume in the present CN6 group. Graphical abstract.


Single-helical formyl β-glucan effectively deliver CpG DNA with poly(dA) to macrophages for enhanced vaccine effects.
Single helical β-glucan is a one-dimensional host that can form a hybrid helix with DNAs/RNAs as delivery systems. However, unmodified β-glucan has a gelling tendency and a single helical conformation is challenging to obtain. Therefore, in this study, we developed a β-glucan formyl derivative with stable single helical conformation and no gelling tendency. Circular dichroism studies found that the formyl-β-glucan could form a hybrid helix with DNA CpG-poly(dA). The hybrid helix delivery system showed improved activation on antigen-presenting cells, thereby upregulating the mRNA and protein levels of inflammatory factors, and had an immune-enhancing effect on ovalbumin (OVA) immunized mice. These results indicate that formyl-β-glucan can be developed as a non-cationic supramolecular DNA delivery platform with low toxicity and high efficiency.


Editorial: single-tablet ibuprofen/double-dose famotidine for reduction of gastric and duodenal ulcers (REDUCE Trials): what can be reduced?
Patients using nonsteroidal anti-inflammatory drugs (NSAIDs) who are at high risk of gastroduodenal ulcer complications often do not receive gastroprotective co-therapy. Fixed-dose combination tablets of an NSAID and a proton-pump inhibitor or misoprostol are intended to improve adherence. Whether the use of these combination tablets will improve adherence and clinical outcome remains largely uninvestigated. Unlike proton-pump inhibitors and misoprostol, the efficacy of histamine-2-receptor antagonists in preventing gastroduodenal ulcers associated with NSAID use is questionable. Nonetheless, a new fixed-dose combination tablet of an NSAID and famotidine will soon be available on the market. The study by Laine et al. is a pooled analysis of two large-scale, carefully designed randomized trials (REDUCE trials) of a fixed-combination tablet of ibuprofen and famotidine on the incidence of endoscopic ulcers. How the study findings may influence clinical practice deserves further consideration.


A review of pulmonary toxicity of different types of quantum dots in environmental and biological systems.
Quantum dots (QDs) are nanoparticles with a particle size of 1-10 nm. Typical QDs are made of compounds such as cadmium sulfide, cadmium selenide, silver sulfide, and indium phosphide, among others. QDs exhibit promising potential for a wide range of applications owing to their excellent optical properties. With the rise in the application of and demand for QDs, QDs accumulation in the environment has increased markedly. QDs enter the pulmonary system via inhalation and trigger pulmonary toxicity. This paper first reviews the pulmonary toxicity of different types of QDs in vivo and in vitro. Regarding acute toxicity, QDs cause changes in cell morphology, cell membrane disruption, cell viability, and pulmonary inflammation. Regarding chronic toxicity, cadmium-based QDs cause pulmonary granulomas and have a potential carcinogenic risk. Second, this paper presents an overview of the pulmonary toxicity mechanism of QDs, involving oxidative stress, inflammation, autophagy, apoptosis, and ferroptosis. It summarizes mitogen-activated protein kinases, nuclear factor κB, nuclear factor-erythroid 2-related factor 2, P53, and Phosphoinositide 3-kinase/AKT signaling pathways in apoptosis and autophagy. Third, it enumerates the physicochemical properties of QDs influencing pulmonary toxicity, ranging from components, surface functional groups, size, and surface charge. Lastly, it outlines the shortcomings of current studies on QDs pulmonary toxicity. The paper concludes with a recommendation discussing research-based improvements in the physicochemical properties of QDs to reduce their release in the environment.


Not debatable.
Science is essential to the economic future and national security. The next US President needs to understand the importance of science, communicate that to the public, and use scientific information properly.


Conchal bowl skin grafting in nasal tip reconstruction: clinical and histologic evaluation.
It is often difficult to achieve an esthetically pleasing cosmetic match when full-thickness skin grafts from periclavicular, preauricular, or postauricular donor sites are used to repair distal nasal defects. This, in large part, is due to the highly sebaceous nature of the skin on the distal aspect of the nose. Our purpose was to describe the benefits of using donor skin from the conchal bowl to repair defects of the nasal tip. The technique of conchal bowl grafting is described. The conchal grafts give an excellent cosmetic result with respect to color and texture match and are time efficient because the donor site can be allowed to heal by secondary intention. The conchal bowl offers an esthetically reliable source of donor skin for full-thickness and perichondrial cutaneous grafts to repair defects of the nasal tip.


A smart film incorporating anthocyanins and tea polyphenols into sodium carboxymethyl cellulose/polyvinyl alcohol for application in mirror carp.
Multifunctional food packaging films were developed based on polyvinyl alcohol (PVA), sodium carboxymethyl cellulose (CMC), tea polyphenol (TP) and black carrot anthocyanin (CA). Results of Zeta potential, scanning electron microscopy, Fourier transform infrared spectroscopy and X-ray diffraction showed that CA enhanced the stability of the particle dispersion system through hydrogen bonding and electrostatic interactions, promoted the compatibility between TP and PVA-CMC (PC) substrates, and enhanced the binding between the components of the films. Because of the interaction of TP and CA, PC-TP-CA films had better water resistance and water vapor barrier properties, thermal stability, antioxidant and antimicrobial properties. PC-CA and PC-TP-CA films exhibited excellent UV-blocking properties. They also showed distinct color responsiveness in the pH range of 2-13, significant sensitivity to ammonia vapor in a short period of time and excellent color stability over 20 days of storage under different conditions. When the film was applied to fish, it was found that PC-TP-CA film could extend the shelf life of fish by 1-2 days and successfully monitor the freshness of the fish in real-time. Considering all the physical and functional properties, the non-toxic and biodegradable PC-TP-CA film has excellent potential as a new multifunctional food packaging material in the future.


Farber's disease (disseminated lipogranulomatosis)--a pathological, histochemical and ultrastructural study--.
The first case of Farber's disease in Japan was reported, which was confirmed clinically, biochemically and pathologically. Soon after birth, the patient started developing hoarseness, stridor, fever, muscle hypotonous with retarded psychomotor functions including incapability of sitting alone and head control, joint swelling, subcutaneous nodules, albuminocytologic dissociation in cerebrospinal fluid, nodular corneal opacity, and abnormal findings in electroencephalogram. Lipid analysis on the material obtained from a subcutaneous nodule confirmed the presence of ceramide. Pathologically, the subcutanoues nodules were made up of granulomatous lesions displaying varied histological pictures, i.e., from cellular to fibrous areas depending on the disease progress. In the beginning, cells were mostly spindle-shaped, and as these cells were getting more round and larger, cells manifested the morphology of foam cells. Spindle-shaped cells were positive for periodic acid-Schiff and acid mucopolysaccharide stainings. This particular substance disappeared almost entirely in typical foam cells. Electron microscopically, the cytoplasm of foam cells was filled with membrane-bound storage inclusions which consisted of so-called curvilinear tubular structures. Morphogenesis of the granulomatous lesions and histochemical and ultrastructural correlation of storage cells in this disorder were discussed.


Drug resistant tuberculosis: Current scenario and impending challenges.
Tuberculosis is still one of the ten leading causes for death worldwide. In spite of the latest medical and health advance gained over a period of time, tuberculosis effectively evades the successful targeting by drugs. The persistence abilities demonstrated by the mycobacteria had surprised the global community, since its discovery and pathogenesis in humans. Emergence and detection of drug resistant mycobacteria (MDR-TB, XDR-TB) had further complicated the treatment regime. Under the aegis of WHO, there is a concerted understanding and effort by the global community to eradicate TB. Towards this goal, novel drug molecules, new vaccine and treatment regime are being developed. Here, our current understanding pertaining to mode of action, molecular mechanisms of novel as well as traditional drug molecules and possible drug resistance mechanism in M. Tuberculosis is reviewed. Recent advances on new vaccination regime are also reviewed as it demonstrated huge potential in containing TB. This knowledge is essential for the development of more effective drug molecules, vaccines and may help in devising new strategy for containing and eradicating TB.


Ambulance snatching: how vulnerable are we?
Out of concern that ambulances might be targeted for hijack for terrorism purposes, we observed security-related behaviors of a cross-section of ambulance crews and their vehicles in Emergency Department ambulance bays. We sent observers to a convenience sample of trauma and suburban Emergency Department ambulance entrances in several states. We observed 151 total ambulance arrivals. Overall, the average time present was 21.5 min, 23.2% of units were left with the engine running, 26.5% were left open, 90.1% were left unattended, 84.1% were unlocked, and 16.6% had a non-crew visitor in the ambulance bay. Several issues were identified demonstrating potential "attractiveness" to individuals who may wish to disrupt Emergency Medical Services or steal an emergency vehicle. We are concerned that this is the case at the majority of ambulance bays in our country. Emergency services agencies should take steps to train their personnel to secure the ambulance.


Three unsuccessful treatments of Helicobacter pylori infection by a highly virulent strain with quadruple antibiotic resistance.
We report a case of an adult patient undergoing three unsuccessful Helicobacter pylori treatments, including proton pump inhibitor (PPI), bismuth subcitrate, metronidazole and tetracycline in 2012, PPI, amoxicillin and clarithromycin in 2013, and PPI, amoxicillin and rifampin in 2014. Following the first treatment, the isolate was metronidazole and ciprofloxacin/levofloxacin resistant. After the second treatment, the isolate was resistant to metronidazole, ciprofloxacin/levofloxacin and rifampin, developing secondary clarithromycin resistance by A2143G mutation and was susceptible only to tetracycline. After the third treatment, the patient still remained H. pylori positive. Patient's strain was highly virulent (cagA (+) , cagE (+) and vacA s1a/m1/i1). The evolution of the patient's disease was from gastroesophageal reflux disease in 2012 to two duodenal ulcers in 2015. Briefly, the infecting strain showed quadruple antibiotic resistance and a transient amoxicillin resistance. Triple clarithromycin-based treatment induced secondary clarithromycin resistance by A2143G mutation, while rifampin resistance caused the third treatment failure. Several options for the next treatment regimens are discussed.


Is pelvic inflammatory disease an indication for treatment with ciprofloxacin?
This pilot study was carried out on 23 gynaecological patients suffering from salpingitis, salpingitis and pelviperitonitis, Douglas' abscess, and vaginal stump abscess. 21 courses were evaluable for clinical efficacy. The diagnoses had been established mainly by pelviscopy and by clinical gynaecological examinations. The dosage was 2 X 500 mg ciprofloxacin orally every 12 h for 7.6 (5-11) days. Cervical smears collected before therapy revealed the most common pathogens to be Escherichia coli and staphylococci, followed by Proteus mirabilis and streptococci. Clinically ciprofloxacin produced a complete cure in 16 patients (76%), and a clear improvement in four patients (19%). One patient left hospital before completing the therapy. Laboratory tests did not reveal any pathological findings, and ophthalmological examinations (fundoscopy, visus, colour perception) on 16 patients, before and after treatment, likewise did not show any changes. In one patient, therapy had to be discontinued after three days because of pruritic exanthema and vertigo. A second patient complained of strong pain behind the eyes and headache. In both patients these symptoms disappeared completely on discontinuation of treatment. The study showed clinical efficacy of orally administered ciprofloxacin in pelvic inflammatory disease.


Diabetes educators: skilled professionals for improving prediabetes outcomes.
Unchecked, the increasing prevalence of prediabetes can be predicted to only expand the numbers of people developing type 2 diabetes and all its associated health ramifications. People with obesity and prediabetes who are able to manage their body weight are known to decrease their risk of developing diabetes. However, making the changes to diet and levels of physical activity is a difficult proposition for many people. Diabetes educators are a group of healthcare professionals trained to work with people who have diabetes on appropriate goal-setting around self-care behaviors including healthy eating and physical activity to better enable them to accomplish the changes needed for better health outcomes. Applying this same skill set to people with prediabetes provides a ready means for addressing the needs of this population to help diminish their risk of developing diabetes.


Prevalence of cervical spondylotic myelopathy.
Patients with signs and/or symptoms of cervical spondylotic myelopathy are frequently encountered in spinal practice. Exact numbers of prevalence or incidence are not known. A literature search was performed by an experienced librarian in Pubmed, Embase, and Scopus. After selection of articles based on titles and abstracts, a full text review was performed. The prevalence of people needing surgical treatment was also estimated in a neurosurgical practice with a population adherence of 1.7 million people and a known referral pattern of the neurologists; all patients operated upon because of cervical spondylotic myelopathy between July 2009 and July 2012 were collected and prevalence calculated. The search of the literature did not reveal any article reporting an incidence or prevalence of cervical spondylotic myelopathy. Eighty of 5,992 patients were operated upon because of a cervical spondylotic myelopathy: 1.6 per 100,000 inhabitants. Surprisingly, an extensive search of the literature did not reveal exact data about the incidence or prevalence of cervical spondylotic myelopathy. The prevalence of surgically treated cervical spondylotic myelopathy was estimated as 1.6 per 100,000 inhabitants. Although the population adherence to the surgical practice is reasonably fixed and referral patterns are known, this estimate will still be too low for various reasons. At best, this estimate is the minimal prevalence of cervical spondylotic myelopathy that has been operated upon. To address the exact incidence or prevalence of cervical spondylotic myelopathy in general or needing surgical treatment, other investigations are warranted.


Ophthalmic surgery in malignant exophthalmos.
Malignant exophthalmos or the ophthalmic component of Graves' disease is a functionally impairing and cosmetically deforming disorder of orbital tissue, separate from the sympathetic effects of thyrotoxicosis. The deposition of immune complexes of thyroglobulin and its antibodies within orbital muscles results in progressive exophthalmos, ophthalmoplegia, chemosis, and lid fullness. Increasing intraorbital edema and optic nerve tension may produce irreversible retinal ischemia. If unresponsive to medical treatment, patients exhibiting increasing loss of visual acuity are therefore candidates for emergency surgery. Early attempts at surgical correction of the mechanical aspect of Graves' ophthalmopathy were unsuccessful. The current technique of transantral orbital decompression, when done before extreme advancement of the ocular disease, is successful and meets the following objectives: It restores visual loss and prevents further deterioration of visual acuity, protects the cornea, restores extraocular muscle movements, decreases intraorbital pressure, produces a satisfactory cosmetic result, and avoids serious complications. Patients with persistent extraocular muscle imbalance or lid lag may ultimately require oculoplastic surgery.


Acute encephalopathy associated with influenza virus infection in a patient with hyperprolinaemia type II.
We report a 4-year-old boy with hyperprolinaemia type II presenting acute encephalopathy associated with influenza virus type A infection. This case suggests that hyperprolinaemia may cause acute encephalopathy under certain conditions.


"Project for a Spatiotemporal Neuroscience" - Brain and Psyche Share Their Topography and Dynamic.
What kind of neuroscience does psychoanalysis require? At his time, Freud in his "Project for a Scientific Psychology" searched for a model of the brain that could relate to incorporate the psyche's topography and dynamic. Current neuropsychoanalysis builds on specific functions as investigated in Affective and Cognitive (and Social) Neuroscience including embodied approaches. The brain's various functions are often converged with prediction as operationalized in predictive coding (PC) and free energy principle (FEP) which, recently, have been conceived as core for a "New Project for Scientific Psychology." We propose to search for a yet more comprehensive and holistic neuroscience that focuses primarily on its topography and dynamic analogous to Freud's model of the psyche. This leads us to what we describe as "Spatiotemporal Neuroscience" that focuses on the spatial topography and temporal dynamic of the brain's neural activity including how they shape affective, cognitive, and social functions including PC and FEP (first part). That is illustrated by the temporally and spatially nested neural hierarchy of the self in the brain's neural activity (second and third part). This sets the ground for developing our proposed "Project for a Spatiotemporal Neuroscience," which complements and extends both Freud's and Solms' projects (fourth part) and also carries major practical implications as it lays the ground for a novel form of neuroscientifically informed psychotherapy, namely, "Spatiotemporal Psychotherapy." In conclusion, "Spatiotemporal Neuroscience" provides an intimate link of brain and psyche by showing topography and dynamic as their shared features, that is, "common currency."


Diagnosis of Pompe's disease using pyridylamino-maltooligosaccharides as substrates of alpha-1,4-glucosidase.
We have developed a sensitive method for the assay of alpha-1,4-glucosidase in cultured skin fibroblasts and muscle tissue using pyridylamino-maltooligosaccharides as fluorescent substrates. This method is useful for the diagnosis of Pompe's disease.


Spike generating smooth muscle cells in mesenteric artery of rats.
Membrane electrical properties of smooth muscle cells at different loci in the vessel wall of rat small mesenteric arteries were studied using glass microelectrodes. Isometric force was measured simultaneously. Penetrations of smooth muscle cells on the adventitial side (outer cells) showed an average resting potential, -43.1 +/- 0.8 mV (n = 24). In outer cells, numerous depolarizing junctional potentials and, to a lesser degree, hyperpolarizing junctional potentials were observed. When current was injected, electrotonic potentials were recorded. Input resistance was 2.2 +/- 0.1 x 10(9) omega (n = 15), suggesting that the low resistance pathways commonly observed in smooth muscle tissue are absent among these cells. Transmural electrical stimulation of nerves elicited spikes and summation of junctional potentials, accompanied by force. TTX virtually abolished these effects of the transmural stimulation. In contrast, cells near the intima (inner cells) had an average resting potential of -65.8 +/- 0.9 mV (n = 37). No spontaneous electrical activity was observed; nor could electrotonic potentials be recorded. Thus, the smooth muscle cells from the outer layer of rat small resistance arteries differ from the inner cells in their lower membrane potentials, generation of spikes, higher input resistance and innervation. Results also suggest that the influence of nerves may be to facilitate opening of voltage-gated Ca2+ channels in innervated cells.


Global preterm births attributable to BTEX (benzene, toluene, ethylbenzene, and xylene) exposure.
Epidemiological studies have shown that long-term exposure to toxic volatile organic compounds, such as benzene, toluene, ethylbenzene, and xylene (BTEX), is associated with preterm births (PTB). However, global PTB attributable to long-term BTEX exposure has not been reported in the literature yet. In this study, we employed a global chemical transport model, GEOS-Chem (Goddard Earth Observing System coupled with chemistry), in conjunction with an epidemiological model, to quantify the global country-specific PTB associated with long-term BTEX exposure at the horizontal resolution of 1 km × 1 km for the year 2015. Model simulated surface annual mean BTEX concentrations in GEOS-Chem have been thoroughly evaluated against global in-situ observations, which demonstrated that model simulated BTEX concentrations fairly agreed with observations but tended to be underestimated in India. Our study found that the global annual total PTB attributable to BTEX was 2.01 million [95% confidence interval (95CI): 1.16-2.70 million] in 2015, with largest contributions from India (28.3%), followed by China (27.5%), Pakistan (6.2%), Indonesia (4.2%), Bangladesh (3.7%) and United States (2.3%). The global annual total PTB due to BTEX exposure accounted for 19.6% (95CI: 11.3-26.4%) relative to the global annual total all-cause PTB (10.24 million) in 2015. Our study has significant implications on air pollution mitigation policy associated with country-specific anthropogenic BTEX emission reductions to achieve the benefit of human health.


Sea-level haemoglobin concentration is associated with greater exercise capacity in Tibetan males at 4200 m.
What is the topic of this review? Recent developments link relatively lower hemoglobin concentration in Tibetans at high altitude to exercise capacity and components of oxygen transport. What advances does it highlight? Haemoglobin concentration (ranging from 15.2 to 22.9 g dl(-1) ) in Tibetan males was negatively associated with peak oxygen (O2 ) uptake per kilogram, cardiac output and muscle O2 diffusion conductance. Most variance in the peak O2 uptake per kilogram of Tibetan males was attributed to cardiac output, muscle diffusional conductance and arterial partial pressure of CO2 . The mechanisms underlying these differences in oxygen transport in Tibetans require additional analyses. Despite residence at >4000 m above sea level, many Tibetan highlanders, unlike Andean counterparts and lowlanders at altitude, exhibit haemoglobin concentration ([Hb]) within the typical sea-level range. Genetic adaptations in Tibetans are associated with this relatively low [Hb], yet the functional relevance of the lower [Hb] remains unknown. To address this, we examined each major step of the oxygen transport cascade [ventilation (VE), cardiac output (QT) and diffusional conductance in lung (DL) and muscle (DM)] in Tibetan males at maximal exercise on a cycle ergometer. Ranging from 15.2 to 22.9 g dl(-1) , [Hb] was negatively associated with peak O2 uptake per kilogram (r = -0.45, P < 0.05) and both cardiac output (QT/kg: r = -0.54, P < 0.02) and muscle O2 diffusion conductance (DM/kg: r = -0.44, P < 0.05) but not ventilation, arterial partial pressure of O2 or pulmonary diffusing capacity. Most variance in peak O2 uptake per kilogram was attributed to QT, DM and arterial partial pressure of CO2 (r(2) = 0.90). In summary, lack of polycythaemia in Tibetans is associated with increased exercise capacity, which is explained by elevated cardiac, muscle and, to a small extent, ventilatory responses rather than pulmonary gas exchange. Whether lower [Hb] is the cause or result of these changes in O2 transport or is causally unrelated will require additional study.


Bone replaces articular cartilage in the rat knee joint after prolonged immobilization.
Lost joint range of motion (ROM) is common in chronic osteoarthritis, alters regional weight-bearing across the articular surfaces, and contributes to loss of cartilage and bone alterations. Limited data exist on the regional effects on joints subjected to chronic losses of ROM. To characterize the regional replacement by bone as part of articular cartilage degeneration after prolonged immobilization. Eleven rat knees were rigidly-immobilized in flexion for 32weeks with contralateral and sham-operated (n=6) knees as controls. Sagittal medial tibial epiphysis histological sections assessed the anterior (non-weight-bearing), middle and posterior (both weight-bearing) regions. We quantified the distribution of collagen I, collagen II, cartilage thickness, glycosaminoglycan (GAG) staining, Mankin scoring, and subchondral bone plate cross-sectional area. Using immunohistochemistry (IHC), we visualized blood vessels, osteoblasts, and mesenchymal stem cells (MSCs). Immobilized cartilage had increased collagen I content in the anterior tibial region with picrosirius red staining (immobilized=61±20%; contralateral=43±12%, p=0.033; sham=20±10%, p=0.028) and collagen I IHC (immobilized=40±10%; contralateral=11±4%, p=0.003; sham=5±3%, p=0.043). Articular cartilage was thinner anteriorly (18±30μm) in immobilized knees versus contralateral (124±40μm, p<0.001) and sham (125±43μm, p=0.043). GAG staining covered 2±4% of the anterior articular area in immobilized knees versus 28±12% contralaterally (p=0.003) and 26±7% in sham (p=0.043). Mankin scores in immobilized knees were 4.7±1.7 versus 0.2±0.4 and 0±0 for contralateral and sham (p=0.003, p=0.042), respectively. The trabecular bone plate area of anterior and posterior regions showed relative loss of cross-sectional area in immobilized knees compared to controls (immobilized/contralateral area ratios of 0.67 and 0.46 respectively, both p=0.003), while the area in the middle region was preserved. Movat's pentachrome stain and CD31 staining showed chondral vascular ingrowth from subchondral bone. Osteocalcin and CD90 MSC staining were decreased in immobilized knees versus contralateral (p=0.003, p=0.036 respectively). Bony replacement characterizes articular cartilage degeneration of knees immobilized for 32weeks in the anterior, non-weight bearing region of the tibia. Replacement of cartilage by bone may have been mediated by chondral vascularization, suggesting irreversible changes. These findings stress the importance of weight-bearing and joint motion to maintain cartilage structure.


Blockage of calcium-sensing receptor improves chronic intermittent hypoxia-induced cognitive impairment by PERK-ATF4-CHOP pathway.
Obstructive sleep apnea-hypopnea syndrome (OSAHS) is involved in cognitive impairment of children. Chronic intermittent hypoxia (CIH) is considered as the critical pathophysiological mechanism of OSAHS. Calcium sensitive receptor (CaSR) mediated apoptosis in many neurological disease models by endoplasmic reticulum stress (ERS)-related pathway. However, little is known about the role of CaSR in OSAHS-induced cognitive dysfunction. In this study, we explored the effect of CaSR on CIH-induced cognitive impairment and possible mechanisms on regulation of PERK-ATF4-CHOP pathway in vivo and in vitro. CIH exposed for 9 h in PC12 cells and resulted in the cell apoptosis, simulating OSAHS-induced neuronal injury. CIH upregulated the level of CaSR, p-PERK, ATF4 and CHOP, contributing to the cell apoptosis. Treated with CaSR inhibitor (NPS-2143) or p-PERK inhibitor (GSK2656157) before CIH exposure, CIH-induced PC12 cell apoptosis was alleviated via inhibition of CaSR by downregulating p-PERK, ATF4 and CHOP. In addition, we established CIH mice model. With CIH exposure for 4 weeks in mice, more spatial memory errors were observed during 8-arm radial maze test. CIH significantly increased apoptotic cells in hippocampus via upregulating cleaved Caspase-3 and downregulating ratio of Bcl-2 to Bax. Besides, treatment of CaSR inhibitor alleviated the hippocampal neuronal apoptosis following CIH with downregulated p-PERK, ATF4 and CHOP, suggesting that CaSR contributed to CIH-induced neuronal apoptosis in hippocampus via ERS pathway. Sum up, our results demonstrated that CaSR accelerated hippocampal apoptosis via PERK-ATF4-CHOP pathway, holding a critical function on CIH-mediated cognitive impairment. Conversely, inhibition of CaSR suppressed PERK-ATF4-CHOP pathway and alleviated cognitive impairment.


Proportion and stage distribution of screen-detected and non-screen-detected colorectal cancer in nine European countries: an international, population-based study.
The effects of recently implemented colorectal cancer screening programmes in Europe on colorectal cancer mortality will take several years to be fully known. We aimed to analyse the characteristics and parameters of screening programmes, proportions of colorectal cancers detected through screening, and stage distribution in screen-detected and non-screen-detected colorectal cancers to provide a timely assessment of the potential effects of screening programmes in several European countries. We conducted this population-based study in nine European countries for which data on mode of detection were available (Belgium, Denmark, England, France, Italy, Ireland, the Netherlands, Slovenia, and Spain). Data from 16 population-based cancer registries were included. Patients were included if they were diagnosed with colorectal cancer from the year that organised colorectal cancer screening programmes were implemented in each country until the latest year with available data at the time of analysis, and if their age at diagnosis fell within the age groups targeted by the programmes. Data collected included sex, age at diagnosis, date of diagnosis, topography, morphology, clinical and pathological TNM information based on the edition in place at time of diagnosis, and mode of detection (ie, screen detected or non-screen detected). If stage information was not available, patients were not included in stage-specific analyses. The primary outcome was proportion and stage distribution of screen-detected versus non-screen detected colorectal cancers. 228 667 colorectal cancer cases were included in the analyses. Proportions of screen-detected cancers varied widely across countries and regions. The highest proportions (40-60%) were found in Slovenia and the Basque Country in Spain, where FIT-based programmes were fully rolled out, and participation rates were higher than 50%. A similar proportion of screen-detected cancers was also found for the Netherlands in 2015, where participation was over 70%, even though the programme had not yet been fully rolled out to all age groups. In most other countries and regions, proportions of screen-detected cancers were below 30%. Compared with non-screen-detected cancers, screen-detected cancers were much more often found in the distal colon (range 34·5-51·1% screen detected vs 26·4-35·7% non-screen detected) and less often in the proximal colon (19·5-29·9% screen detected vs 24·9-32·8% non-screen detected) p≤0·02 for each country, more often at stage I (35·7-52·7% screen detected vs 13·2-24·9% non-screen detected), and less often at stage IV (5·8-12·5% screen detected vs 22·5-31·9% non-screen detected) p<0·0001 for each country. The proportion of colorectal cancer cases detected by screening varied widely between countries. However, in all countries, screen-detected cancers had a more favourable stage distribution than cancers detected otherwise. There is still much need and scope for improving early detection of cancer across all segments of the colorectum, and particularly in the proximal colon and rectum. Deutsche Krebshilfe.


Profile of the risk of death after septic shock in the present era: an epidemiologic study.
To investigate mortality of ICU patients over a 3-month period after an initial episode of septic shock and to identify factors associated with mortality. Prospective multicenter observational cohort study. Fourteen ICUs from 10 French nonacademic and university teaching hospitals. All consecutive adult patients with septic shock admitted between October 2009 and September 2011 were eligible. None. Multivariable analyses were performed using a Cox proportional hazard model and a flexible extension of the Cox model. In total, 1,495 of 10,941 patients (13.7%) had septic shock and 1,488 patients (99.5%) were included. Median age was 68 years (range, 58-78 yr). The majority of admissions (84%) were medical. Median (interquartile range) Simplified Acute Physiological Score II and Sequential Organ Failure Assessment were, respectively, 56 (45-70) and 11 (9-14). ICU and hospital mortality were, respectively, 39.4% and 48.6%. At 3 months, 776 patients (52.2%) had died. Factors significantly associated with increased risk of death in the multivariable Cox model were older age, male sex, comorbidities (immune deficiency, cirrhosis), Knaus C/D score, and high Sequential Organ Failure Assessment score. Flexible analyses indicated that the impact of Sequential Organ Failure Assessment score was greatest early after septic shock, while the onset of the effect of age, nosocomial infection, and cirrhosis was later. This is the most recent large-scale epidemiological study to investigate medium-term mortality in nonselected patients hospitalized in the ICU for septic shock. Advances in early management have improved survival at the initial phase, but risk of death persists in the medium term. Flexible modeling techniques yield insights into the profile of the risk of death in the first 3 months.


Acquisition of remifentanil self-administration: Enhanced in female rats but no effect of adolescent stress exposure.
Animal models of acquisition have been vital in shaping our understanding of vulnerability factors that influence susceptibility to drugs of abuse. Decades of research substantiates a number of biological, environmental, and behavioral factors that predict vulnerability - many of which have been important in the development of early intervention efforts in humans. The goal of the present study was to examine the acquisition of a synthetic opioid derivative in 66 adult male and female Long-Evans rats following histories of stress exposure during adolescence. Stress-exposed rats were subjected to a mild stress paradigm, which included alternating exposure to synthetic fox feces and physical restraint for eight days. Following stress induction and assessment, all rats were implanted with intravenous catheters in order to self-administer remifentanil (1 μm/kg/infusion) with no prior operant training. Acquisition of remifentanil self-administration was measured over 15 days. Findings indicate that regardless of stress condition, female rats acquired remifentanil self-administration sooner and emitted more active lever presses than males. Stress exposed animals exhibited increased anxiety-like response compared to the control group following exposure to stress, operationalized as decreased exploratory behavior on an Elevated Plus Maze. However, these effects were not expressed as significant differences in self-administration by stress. Together, these findings indicate that sex differences are evident in remifentanil self-administration.


Effects of Long-term Use of Proton Pump Inhibitors on Systemic Arterial Stiffness and Pulse Wave Velocity.
Proton pump inhibitors (PPIs) are among the most widely prescribed agents. Although PPIs are widely regarded as harmlesss, long-term use of PPIs (LTUPPI) can have the potential to increase the risk of developing cardiovascular (CV) disease (CVD). Pulse wave velocity (PWV) is a good indicator of arterial stiffness. Several studies show a relationship between LTUPPI and CVD. However, the association between LTUPPI and PWV or arterial stiffness has not been reported. Patients (n=64) with LTUPPI and controls (n=91) were included. PWV, glucose, creatinine, total cholesterol, triglyceride, low-density lipoprotein cholesterol, cholesterol, highdensity lipoprotein cholesterol, and magnesium levels were measured. In the LTUPPI group, PWV was greater than in controls (9.08±2.04 vs. 7.77±1.52 m/s, respectively, p=0.01); 34.4% of patients and 8.8% of controls had PWV levels >10 m/s (p=0.000). Multiple logistic regression analysis showed age (p<0.001) and LTUPPI (p=0.024) as predictors of elevated PWV. PWV values are increased in patients with LTUPPI compared to controls independently of conventional CV risk factors. Measurement of PWV and other arterial stiffness parameters in cases with LTUPPI may be useful to predict possible CVD. Studies involving greater numbers are needed to confirm these findings.


Artificial embolization with isobutyl-2-cyanoacrylate for the treatment of carotid-ophthalmic aneurysm.
A large carotid-ophthalmic aneurysm was successfully obliterated by the combined treatment of clipping the aneurysmal neck and intraaneurysmal injection of isobutyl-2-cyanoacrylate. Reflux of the glue into the artery was prevented by temporary trapping of the carotid artery. The obliteration of an aneurysm with isobutyl-2-cyanoacrylate is an effective procedure in cases where clipping of the aneurysmal neck is not completed due to technical difficulties.


In Vitro Evaluation of the Antimicrobial Properties of Nanoparticles as New Agents Used in Teat Sealants for Mastitis Prevention in Dry Cows.
Mastitis prevention and treatment in dry cows are complex issues with limited solutions. The most common is intramammary antibiotic treatment. However, the effectiveness of this treatment varies among countries and even within herds in the same region. Therefore, it is necessary to develop new strategies for dry cow therapy. Metal nanoparticles (NPs), which have strong biocidal properties for treating diseases caused by bacteria, fungi, and algae, are increasingly used to reduce antibiotic use. In this study, AuNPs, CuNPs, AgNPs, PtNPs, NP-FeCs, and their triple complexes were used at different concentrations to evaluate their practical use in treating cows during their dry period. The nanoparticles were in hydrocolloid form and were added separately to form a mixture with beeswax, a mixture with oil, or a mixture based on vegetable glycerin and propylene glycol. The NPs' concentrations were 0.5, 1, 2, and 5 ppm. Gram-positive and Gram-negative bacteria, and fungi isolated from cows diagnosed with mastitis were used to determine pathogen viability. The results indicated that AuNPs, CuNPs, AgNPs, and their complexes show biocidal properties against mastitis pathogens. AgNPs at 5 ppm had the strongest biocidal properties and reduced Streptococcus agalactiae's survival rate by 50%; however, the nanoparticle complexes showed poor synergism. The strongest biocidal properties of NPs in wax and in glycerin mixed with glycol were shown against Escherichia coli. Additionally, low nanoparticle concentrations showed no cytotoxicity for BME-UV1 bovine cells, suggesting that these mixtures might be used for further in vivo testing.


An X-Ray C-Arm Guided Automatic Targeting System for Histotripsy.
Histotripsy is an emerging noninvasive, nonionizing and nonthermal focal cancer therapy that is highly precise and can create a treatment zone of virtually any size and shape. Current histotripsy systems rely on ultrasound imaging to target lesions. However, deep or isoechoic targets obstructed by bowel gas or bone can often not be treated safely using ultrasound imaging alone. This work presents an alternative x-ray C-arm based targeting approach and a fully automated robotic targeting system. The approach uses conventional cone beam CT (CBCT) images to localize the target lesion and 2D fluoroscopy to determine the 3D position and orientation of the histotripsy transducer relative to the C-arm. The proposed pose estimation uses a digital model and deep learning-based feature segmentation to estimate the transducer focal point relative to the CBCT coordinate system. Additionally, the integrated robotic arm was calibrated to the C-arm by estimating the transducer pose for four preprogrammed transducer orientations and positions. The calibrated system can then automatically position the transducer such that the focal point aligns with any target selected in a CBCT image. The accuracy of the proposed targeting approach was evaluated in phantom studies, where the selected target location was compared to the center of the spherical ablation zones in post-treatment CBCTs. The mean and standard deviation of the Euclidean distance was 1.4 ±0.5 mm. The mean absolute error of the predicted treatment radius was 0.5 ±0.5 mm. CBCT-based histotripsy targeting enables accurate and fully automated treatment without ultrasound guidance. The proposed approach could considerably decrease operator dependency and enable treatment of tumors not visible under ultrasound.


A bifunctional electrochemical sensor for simultaneous determination of electroactive and non-electroactive analytes: A universal yet very effective platform serving therapeutic drug monitoring.
A novel electrochemical sensor for therapeutic drug monitoring (TDM) of antibiotic Zavicefta was developed in this work. The main components of Zavicefta are ceftazidime (CFZ) and avibactam (AVI), wherein CFZ can be oxidized directly on electrode surface, while AVI is non-electroactive. In order to realize the simultaneous detection of the two analytes on one sensor, we elaborately constructed a dual-template molecularly imprinted polymer (MIP) modified electrode with CFZ and AVI as the templates, and further developed a dual-signal strategy. During detection, due to the inhibition effect caused by rebinding of MIP to the targets, the peak current of probe ferricyanide ([Fe(CN)6]3-) showed obvious suppression. Meanwhile, a new peak appeared, which originated from the oxidation of CFZ. The proposed sensor presented a wide linear range of 50-1000 μM for CFZ and 1-1000 μM for AVI, with the respective detection limit of 35 μM and 0.5 μM (S/N = 3). Owing to the imprinting effect of MIP, the sensor displayed excellent selectivity and anti-interference ability, which was successfully applied for TDM of CFZ and AVI in human serum and a live rabbit. The results agreed well with those from HPLC. This work is expected to offer a promising avenue for simultaneous measurement of electroactive and non-electroactive substances, and extend the potential of electrochemical sensors in medical field.


Monitoring tumor response with [18F]FMAU in a sarcoma-bearing mouse model after liposomal vinorelbine treatment.
Previous studies have shown that the accumulation level of FMAU in tumor is proportional to its proliferation rate. This study demonstrated that 2'-deoxy-2'-[(18)F]fluoro-β-d-arabinofuranosyluracil ([(18)F]FMAU) is a promising PET probe for noninvasively monitoring the therapeutic efficacy of 6% PEGylated liposomal vinorelbine (lipo-VNB) in a subcutaneous murine NG4TL4 sarcoma mouse model. Female syngenic FVB/N mice were inoculated with NG4TL4 cells in the right flank. After tumor size reached 150 ± 50 mm(3) (day 0), lipo-VNB (5mg/kg) was intravenously administered on days 0, 3 and 6. To monitor the therapeutic efficacy of lipo-VNB, [(18)F]FMAU PET was employed to evaluate the proliferation rate of tumor, and it was compared with that observed from [(18)F]FDG/[(18)F]fluoroacetate PET. The expression of proliferating cell nuclear antigen (PCNA) in tumor during treatment was determined by semiquantitative analysis of immunohistochemical staining. A significant inhibition (p<0.001) in tumor growth was observed on day 3 after a single dose treatment. The tumor-to-muscle ratio (T/M) derived from [(18)F]FMAU-PET images of lipo-VNB-treated group declined from 2.33 ± 0.16 to 1.26 ± 0.03 after three doses of treatment, while that of the control remained steady. The retarded proliferation rate of lipo-VNB-treated sarcoma was confirmed by PCNA immunohistochemistry staining. However, both [(18)F]FDG and [(18)F]fluoroacetate microPET imaging did not show significant difference in T/M between the therapeutic and the control groups throughout the entire experimental period. Lipo-VNB can effectively impede the growth of NG4TL4 sarcoma. [(18)F]FMAU PET is an appropriate modality for early monitoring of the tumor response during the treatment course of lipo-VNB.


Correlation between magnetic resonance imaging of the heart and cardiac anatomy.
An understanding of anatomy forms the cornerstone for accurate interpretations of pathologic alterations. In this article, we present cardiac magnetic resonance images and the corresponding sections of normal hearts obtained at autopsy and cut in planes parallel and perpendicular to the ventricular septum in addition to the standard anatomic orthogonal planes (coronal, sagittal, and transverse). This correlation demonstrates the ability of magnetic resonance imaging to display cardiac anatomy accurately and noninvasively. Because magnetic resonance imaging provides excellent contrast between flowing blood and cardiac walls and has the capacity to provide direct images in multiple planes without inherent difficulties, this procedure has advantages over other currently available imaging techniques.


Encapsulation of low lipophilic and slightly water-soluble dihydroartemisinin in PLGA nanoparticles with phospholipid to enhance encapsulation efficiency and in vitro bioactivity.
PLGA nanoparticles have been widely utilised to encapsulate lipophilic drugs for sustained release. This study was to enhance encapsulation efficiency and drug loading for the poorly lipophilic drug dihydroartemisinin (DHA) in PLGA nanoparticles, where amphiphilic phospholipid was employed as the intermediate. DHA-phospholipid complex formulation was optimised using the response surface method. DHA-phospholipid complex-nanoparticles (DHA-PLC-NPs) were prepared using the solvent evaporation method. The particle size, zeta potential, entrapment efficiency and drug loading of the nanoparticles were 265.3 ± 7.9 nm, -21.4 ± 6.3 mV, 74.2 ± 6.5% and 2.80 ± 0.35%, respectively. Compared with the rapidly released free form, DHA underwent sustained release from the nanoparticles. DHA-PLC-NPs presented stronger cell proliferative inhibition than DHA treatment alone and apoptosis was obviously induced after DHA-PLC-NPs treatment. Phospholipid complexes are useful intermediate to improve the lipophilicity of drugs, the interaction with the hydrophobic core of PLGA and the encapsulation efficiency of poorly lipophilic drugs in polymeric nanoparticles.


Seismic evidence of pop-up tectonics beneath the Shillong Plateau area of Northeast India.
Our detailed 3-D seismic tomographic assimilation using high-quality phase arrival time data recorded by the local seismographic network demonstrated that heterogeneities in the crustal faults have contributed significantly to the pop-up tectonics beneath the Shillong Plateau, characterized by high-V and low-σ. The major seismogenic faults, namely, the north-dipping Dapsi thrust in association with Dauki fault in the south and south dipping Brahmaputra fault in the north, located either side of the Shillong Plateau that acted as the causative factors for the pop-up, which attributed to the lithostatic (high-V, low-σ) and sedimentary (low-V, high-σ) load, respectively. Seismicity is found confined to a depth ≤ 60 km. Uneven distribution of structural heterogeneities in the upper crust is responsible for earthquake genesis of varying strengths. It is intriguing to note that high-velocity anomalies and low-ϭ in the uppermost crust, interpreted as the Shillong Plateau that acted as a geometric asperity and the juxtaposition of high-V and low-V became the source zone of the 1897 Shillong earthquake (Ms 8.7) as a novel observation for the region. Structural heterogeneities are distinctly distributed between low-V, high-σ and high-V, low-σ in the lower crust plays a major role for future intense seismogenesis due to differential strain accumulation.


Biochemical and chemical characterization of Cynara cardunculus L. extract and its potential use as co-adjuvant therapy of chronic myeloid leukemia.
Ancient mediterranean diet was characterized by consuming the spontaneous forms of Cynara cardunculus L. (CCL), commonly called artichoke. Cultivated and/or spontaneous forms of CC studies have demonstrated that methanol extract of CCL flower and/or cynaropicrin showed remarkable anti-proliferative activity in vitro models of leukocyte cancer cell. Chronic myeloid leukemia (CML) is associated with a reciprocal translocation of the long arms of chromosomes 9 and 22 generating the BCR/ABL fusion gene, translated in the p210BCR/ABL oncoprotein kinase. This chimeric protein is the target of a kinase inhibitor, imatinib, but the development of mutations in the ABL kinase domain resulting in drug resistance and several approaches to overcoming resistance have been study. In this concern, we investigated the effect of CCL extract on human K562 CML and K562 imatinib resistant (IMAR) cell proliferation and on p210BCR/ABL expression. Chemical characterization of the CCL extracts was performed by GC/MS analysis and semipreparative RP-HPLC chromatography. Structural characterization of compounds was assessed by 1H-13C NMR and LC/MS analysis. The effects of CCL extracts on the proliferation of K562 CML human cell line and K562 IMAR were screened by MTT assay. The p210BCR/ABL mRNA and protein expressions were analyzed by qRT-PCR and Western blot techniques respectively. We demonstrate that CCL extract affect cell viability of both K562 CML human cell line and K562 IMAR. The biocomponents of CCL were chemical characterized and we identify cynaropicrin and its deacyl derivative having the capability to down-regulate the p210BCR/ABL oncoprotein. Our study suggests that the use of those molecules could represent a novel and promising strategy to potentiate the ability of imatinib or of its analogues to induce cancer growth arrest in CML and to delay or overcome the resistance of CML to chemotherapy.


Aortic valve sclerosis as a marker of active atherosclerosis.
Aortic sclerosis is a calcific disease of the aortic valvular leaflets defined as focal leaflet thickening without significant obstruction to left ventricular outflow. Several clinical factors are associated with calcific aortic valve disease, including male sex, smoking, hypertension, age, hypercholesterolemia, and diabetes. Histologic and biochemical studies suggest similarities between the mechanisms involved in the development of aortic sclerosis and atherosclerosis, suggesting these two diseases may share common pathophysiologic mechanisms. In a recent prospective trial, the presence of aortic sclerosis was associated with an approximately 50% increase in cardiovascular mortality and myocardial infarction, even after correction for age, gender, known coronary artery disease, and clinical factors associated with a aortic sclerosis.


Does depressed persons with non-cardiovascular morbidity have a higher risk of CVD? A population-based cohort study in Sweden.
Depression often co-exists with non-cardiovascular morbid conditions. Whether this comorbidity increases the risk of cardiovascular disease has so far not been studied. Thus, the aim of this study was to determine if non-cardiovascular morbidity modifies the effect of depression on future risk of CVD. Data was derived from the PART study (acronym in Swedish for: Psykisk hälsa, Arbete och RelaTioner: Mental Health, Work and Relationships), a longitudinal cohort study on mental health, work and relations, including 10,443 adults (aged 20-64 years). Depression was assessed using the Major Depression Inventory (MDI) and self-reported data on non-cardiovascular morbidity was assessed in 1998-2000. Outcomes of CVD were assessed using the National Patient Register during 2001-2014. Both depression (HR 1.5 (95% CI, 1.1, 2.0)) and non-cardiovascular morbidity (HR 2.0 (95% CI, 1.8, 2.6)) were associated with an increased future risk of CVD. The combined effect of depression and non-cardiovascular comorbidity on future CVD was HR 2.1 (95%, CI 1.3, 3.4) after adjusting for age, gender and socioeconomic position. Rather similar associations were seen after further adjustment for hypertension, diabetes and unhealthy lifestyle factors. Persons affected by depression in combination with non-cardiovascular morbidity had a higher risk of CVD compared to those without non-cardiovascular morbidity or depression alone.


Effects of exogenous melatonin and glutathione on zinc toxicity in safflower (Carthamus tinctorius L.) seedlings.
The phytotoxicity caused by 500 μM ZnSO4.7H2O and its detoxifying by co-application of 100 μM of MT melatonin (MT) and glutathione (GSH) in 6-week-old safflower plants have been investigated. Reduced biomass production and total chlorophyll content on the one hand and increased content of hydrogen peroxide (H2O2), malondialdehyde (MDA) with increase in lipoxygenase activity, on the other hand, showed Zn- induced oxidative damage in safflower seedlings. When MT, GSH and especially MT + GSH exogenously were applied to Zn-stressed seedlings, the content of H2O2, MDA and the activity of lipoxygenase considerably decreased. In Zn- treated seedlings, the application of these signaling molecules led to a considerable increment in ascorbate (ASC), GSH and phytochelatin (PC) contents along with the induction of activity of antioxidant enzymes including ascorbate-glutathione cycle enzymes when compared with the plants stressed with Zn only. In Zn-stressed safflower seedlings treated with MT, GSH and MT + GSH, decreased activity of enzymes involved in glyoxalase system may be associated with the role of MT and GSH in reducing Zn uptake and reducing Zn-induced toxicity and subsequently, lower plant's defense responses. The data showed that the effects of MT and GSH, in particular, the combination of these two molecules in reducing Zn uptake and diminishing its accumulation in the shoots of safflower seedlings, and also the participation of MT and GSH on increasing plant ability to tolerate high amount of Zn through stimulation of various antioxidant defense systems suggest them as suitable candidates to better the survival of safflower in soils contaminated with Zn excess.


Correlation of phylogenetic clade diversification and in vitro infectivity differences among Cosmopolitan genotype strains of Chikungunya virus.
Cosmopolitan genotypes of Chikungunya virus caused the large-scale febrile disease outbreaks in the last decade in Asian and African continents. Molecular analyses of these strains had revealed significant genetic diversification and occurrence of novel mosquito-adaptive mutations. In the present study we looked into whether the genetic diversification has implications in the infectivity phenotype. A detailed sequence and phylogenetic analyses of these virus strains of Indian Ocean lineage from Kerala, South India from the years 2008 to 2013 identified three distinct genetic clades (I, II and III), which had presence of clade-specific amino acid changes. The E2 envelope protein of the strains from the years 2012 to 2013 had a K252Q or a novel K252H change. This site is reported to affect mosquito cell infectivity. Most of these strains also had the E2 G82R mutation, a mutation previously identified to increase mammalian cell infectivity, and a novel mutation E2 N72S. Positive selection was identified in four sites in the envelope proteins (E1 K211E, A226V and V291I; E2 K252Q/H). In infectivity analysis, we found that strains from clade III had enhanced cytopathogenicity in HEK293 and Vero cells than by strains representing other two clades. These two strains formed smaller sized plaques and had distinctly higher viral protein expression, infectious virus production and apoptosis induction in HEK293 cells. They had novel mutations R171Q in the nsP1; I539S in nsP2; N409T in nsP3; and N72S in E2. Our study identifies a correlation between phylogenetic clade diversification and differences in mammalian cell infectivity phenotype among Cosmopolitan genotype CHIKV strains.


Human NORs, comprising rDNA arrays and functionally conserved distal elements, are located within dynamic chromosomal regions.
Human nucleolar organizer regions (NORs), containing ribosomal gene (rDNA) arrays, are located on the p-arms of acrocentric chromosomes (HSA13-15, 21, and 22). Absence of these p-arms from genome references has hampered research on nucleolar formation. Previously, we assembled a distal junction (DJ) DNA sequence contig that abuts rDNA arrays on their telomeric side, revealing that it is shared among the acrocentrics and impacts nucleolar organization. To facilitate inclusion into genome references, we describe sequencing the DJ from all acrocentrics, including three versions of HSA21, ∼3 Mb of novel sequence. This was achieved by exploiting monochromosomal somatic cell hybrids containing single human acrocentric chromosomes with NORs that retain functional potential. Analyses revealed remarkable DJ sequence and functional conservation among human acrocentrics. Exploring chimpanzee acrocentrics, we show that "DJ-like" sequences and abutting rDNA arrays are inverted as a unit in comparison to humans. Thus, rDNA arrays and linked DJs represent a conserved functional locus. We provide direct evidence for exchanges between heterologous human acrocentric p-arms, and uncover extensive structural variation between chromosomes and among individuals. These findings lead us to revaluate the molecular definition of NORs, identify novel genomic structural variation, and provide a rationale for the distinctive chromosomal organization of NORs.


Current efforts and trends in the treatment of NASH.
Of all the aspects of non-alcoholic fatty liver disease (NAFLD), the slowest advances have occurred in the therapeutic field. Thirty-five years after its formal description and after 15 years of intense scrutiny from researchers worldwide, there is still no approved drug for the treatment of non-alcoholic steatohepatits (NASH). In the meantime, progress in the understanding of pathophysiology, diagnosis - both invasive and non-invasive, epidemiology and even natural history have been substantial or, at times, spectacular. In contrast, hepatitis C virus (HCV) therapy underwent constant improvement and even before the great acceleration of the past few years, patients were already being offered approved therapies that were increasingly more efficient. What then explains such a slow pace of therapeutic advances in NASH, and will this change in the near future? Here we will review commonly-held myths that have diverted attention from therapy of NASH, obstacles that have slowed down industrial development of drugs for this indication, and recent achievements that will create better conditions for drug development programs. We will also briefly review current knowledge of non-pharmacological and pharmacological management in this early era of NASH therapies.


Iliolumbar vein: a challenge for the exposure of the L4-5 disc in the anterior approach to the lumbar spine.
Anterior lumbar spine arthrodesis has been increasingly prescribed. In order to obtain better exposure of the intervertebral discs, it is necessary to identify vascular structures depending on the level to be approached. Systematic ligation of the iliolumbar vein has been suggested for access to the L4-L5 level, which may be technically challenging. The goal of the present study was to determine a safe limit for separating the iliolumbar vein safely without the need for its ligation. In total, 2284 patients involving the topography of the iliolumbar vein were included. If this vein was up to 5 mm distant from the inferior border of the L4-L5 intervertebral disc, its ligature was performed. In cases that the distance was greater than 5 mm, only the retraction was performed without ligature. A total of 115 ligatures were necessary (5% of cases). Among the 2169 cases with no ligature, bleeding due to ruptures occurred during traction in only 55 patients (3% of cases). The time taken for ligation ranged from five minutes to thirty-two minutes, with an average of 18.3 min per ligature. In cases in which ligatures were needed (distance less than 5 mm), there was loosening of the ligatures leading to bleeding in 23 cases (20% of ligatures). Systematic ligature is not necessary for accessing the anterior route to the L4-L5 level, leading to a reduction in the time of surgery and avoiding serious vascular injuries that can occur.


On the correlation between single-frequency impedance measurements and human skin permeability to water.
The objective of this study was to quantitatively compare measurements of tritiated water permeability with impedance determined at either 100 or 1000 Hz using an LCR databridge on the same pieces of skin. A previously published expression based on a simple circuit of a parallel resistor and constant phase element (CPE) was used to relate (RPARA) measured at different frequencies to the DC resistance (RskinA) and the steady-state skin permeability of tritiated water (kp). Using this analysis, kp and (RPARA) data from three laboratories were shown to be consistent with each other, and kp and (RskinA) estimated from (RPARA) were linearly correlated. Compared with urea and mannitol, which are known to permeate skin through a polar pathway, the value of kp for water was found to be about two times larger than expected for transport through only the polar pathway, suggesting an approximately equal contribution from the lipophilic pathway. Equations relating kp to (RPARA) and (RskinA) were used to compare on a consistent basis proposed tests for identifying and excluding damaged skin from chemical absorption studies. The criterion of 20 kΩ cm2 for (RskinA) corresponds to a tritiated water permeability of 3.2×10(-3) cm/h, which should exclude damaged skin without screening undamaged but higher permeability skin samples from study.


Comparison of two leukocytapheresis protocols in a case of idiopathic hypereosinophilic syndrome.
Hypereosinophilic syndrome (HEOS) is rare, and the efficacy of leukocytapheresis in this context is unclear. We here report the successful treatment of a patient with idiopathic HEOS with four leukocytapheresis procedures using two protocols. A 4-year-old female presented with cardiac and respiratory dysfunction, and WBC of 225 K/μL with 96% eosinophils. Leukocytapheresis was started after initiation of methylprednisolone and hydroxyurea. She received two leukocytapheresis with polymorphonuclear cell (PMN) protocol, followed by initiation of imatinib therapy, then two leukocytapheresis with mononuclear cell (MNC) protocol. After the fourth leukocytapheresis, her WBC decreased to 69 K/μL with 82% eosinophils. She was discharged on hospital day 21 under stable condition with WBC of 22 K/μL with 86% eosinophils. WBC count and eosinophil percentage continued to decrease, and were 6.4 K/μL and 52% by 2 weeks and 3.9 K/μL and 4.9% by 3 months after discharge, respectively. WBC and absolute eosinophil (aEO) counts decreased by an average of 29.0 and 30.4% per leukocytapheresis, respectively. Normalized to estimated blood volume, procedures with PMN and MNC protocols changed, on average, WBC by -10.7 and -12.1%, aEO by -10.4 and -13.4%, platelet by -8.1 and -19.2%, and fluid balance by -129 and -47 mL, respectively. Leukocytapheresis was effective in decreasing WBC and aEO counts in HEOS, with PMN and MNC protocols achieving similar reductions. However, PMN protocol resulted in greater negative fluid balance and MNC protocol resulted in greater platelet loss. J. Clin. Apheresis 31:481-489, 2016. © 2015 Wiley Periodicals, Inc.


[Psychiatric disorders and fitness to drive an automobile. An overview].
The revised version of the guidelines for driving ability and the new driving license decree in Germany are outlined regarding forensic implications, general rules, and guidelines for psychiatric illness. Patients suffering from acute organic psychosis, severe dementia, acute schizophrenia, mania, severe depression, and alcoholism must be seen as unable to drive cars. Regarding effects of psychotropic medication on driving performance, multiple data with healthy volunteers are available, with very few patients, however. Based on new data showing differences between older and newer antidepressants and antipsychotics, individual drug selection is strongly recommended.


The long road of pain: chronic pain increases perceived distance.
Spatial perception is sensitive to the energetic costs required to perform intended actions. For example, hills look steeper to people who are fatigued or burdened by a heavy load. Similarly, perceived distance is also influenced by the energy required to walk or throw to a target. Such experiments demonstrate that perception is a function, not just of optical information, but also of the perceiver's potential to act and the energetic costs associated with the intended action. In the current paper, we expand on the notion of "cost" by examining perceived distance in patients diagnosed with chronic pain, a multifactorial disease, which is experienced while walking. We found that chronic pain patients perceive target distances to be farther away compared with a control group. These results indicate the physical, and perhaps emotional, costs of chronic pain affect spatial perceptions.


[The heart goes to the war: a review of the so-called "soldier's heart" or "irritable heart of soldiers" syndrome].
The paper deals with a form of functional heart disorder that caused substantial disability among men in military service. By viewing the condition through the dual lenses of history and modern medical knowledge we can analyse the syndrome and trace the changing medical and social attitudes to it. The disorder is still now present after harrowing events, including natural disasters, assault of individuals, episods of mass violence and combat. A historical review of the syndrome is also useful in extending our understanding of the natural history of stress reactions, their prognostic indicators and the way in which we can intervene to reduce the effects of trauma.


Evidence for a resident subset of cells with SP phenotype in the C2C12 myogenic line: a tool to explore muscle stem cell biology.
Muscle satellite cells are heterogeneous and present functional disparities, some of them behaving as multipotent stem cells. Yet their phenotype is obscure and their isolation remains elusive. The ability to purify stem cells from a wide variety of tissues by using Hoechst 33342 staining/FACS methods has permitted access to this category of cells (side population, or SP) in a manner independent of antibodies. Here, we show that the C2C12 myogenic line comprises a minor population of cells with SP phenotype. These cells are growth-arrested and delayed in their ability to differentiate. Dye efflux in C2C12-derived SPs is likely mediated by mdr1a, whose overexpression results in increased dedifferentiation. Interestingly, growth-arrested SPs rapidly appear in purified MP populations, thus suggesting a dynamic equilibrium among different states of differentiation. Finally, transcriptional profiling of C2C12-derived SP and MP cells corroborates the many similarities of SP to stem cells.


Magnitude and direction of green-up date in response to drought depend on background climate over Mongolian grassland.
Increasing drought is one major consequence of ongoing global climate change and is expected to cause significant changes in vegetation phenology, especially for naturally vulnerable ecosystems such as grassland. However, the linkage between the response characteristic of green-up date (GUD) to drought and background climate remains largely unknown. Here, we focused on how the GUD of Mongolian grassland responds to extreme drought events (EDE). We first extracted the GUD from the MODIS Enhanced Vegetation Index data during 2001-2020 and identified the preseason EDE using the standardized precipitation evapotranspiration index data. Subsequently, we quantified the response of GUD to preseason EDE (DGUD) in each pixel as the difference in GUD between drought and normal years. The effect of 12 factors on DGUD was analyzed using the random forest algorithm. The results showed that the GUD under EDE may delay or advance by > 20 days compared to normal years. For the regions with mean annual temperature > -2 °C, the GUD was delayed under EDE due to the dominant role of water restriction on GUD, while the GUD was advanced under EDE in colder areas due to the warmer temperature during drought. However, the magnitude of delay in GUD under drought was greater in regions with less precipitation and more severe droughts. Our results could help to develop appropriate management strategies to mitigate the impacts of drought on grasslands.


Use of intraventricular tissue plasminogen activator and Guglielmi detachable coiling for the acute treatment of casted ventricles from cerebral aneurysm hemorrhage: two technical case reports.
We report two cases of massive intraventricular hemorrhage resulting from subarachnoid hemorrhage. Both patients had experienced a ruptured cerebral aneurysm and were initially moribund. The patients were treated with Guglielmi detachable coiling and then administration of intraventricular tissue plasminogen activator (tPA). Rapid clot resolution was demonstrated radiographically in both. Both patients survived and had a meaningful functional neurological recovery. These are the first reported cases of the acute use of intraventricular tPA after Guglielmi detachable coiling treatment for ruptured cerebral aneurysm. A 59-year-old woman and a 44-year-old man presented with high-grade subarachnoid hemorrhage. Both had had extensive casting of their ventricular systems with blood. The patients were treated with Guglielmi detachable coiling thrombosis of the aneurysm and then intraventricular administration of tPA for dissolution of blood clots. Both patients survived; one is able to carry out activities of daily living with moderate assistance, and the other is able to communicate with his family. This is a novel method to manage patients with high-grade aneurysms with massive intraventricular blood clots. The tPA reduced the mass effect of the blood clot, possibly helping to improve the neurological grade; in addition, the administration of tPA helped keep the external ventricular drains functional, enabling treatment of the acute hydrocephalus. The safety of administering tPA after endovascular thrombosis was demonstrated in these two patients. Further investigation is required to determine the applicability of this approach on a broader scale.


Miracle cells for natural dentistry - A review.
Stem cells are undifferentiated cells that can differentiate into specialized cells. Recently, enormous growth has been seen in the recognition of stem cell-based therapies, which have the potential to ameliorate the life of patients with conditions that span from Parkinson's disease to cardiac ischemia to bone or tooth loss. This research has produced new but unexplored possibilities in the regeneration of different organs and tissues. Presently, research is focused on the proficiency of stem cells and their utilization in dentistry, which is gaining interest. The tooth is nature's "esteem" for these precious stem cells and there are a number of these cells in permanent and primary teeth, as well as in the wisdom teeth. Dental stem cells are easy, convenient, and affordable to collect. They hold promise for a range of very potential therapeutic applications, such as in the treatment of cancer, spinal cord injury, brain damage, myocardial infarction, hearing loss, diabetes, wound healing, baldness, etc. Since these cells were used to regenerate damaged tissue in medical therapy successfully, it is possible that the dentist in future might use stem cell to regenerate lost or damaged dental and periodontal structures. This paper reviews the current concepts, characteristics of stem cells in regeneration, and its subsequent uses in dentistry.


Tl(I) and Tl(III) induce reticulum stress in MDCK cells.
The effects of the exposure of proliferating MDCK cells to thallium [Tl(I) or Tl(III)] on cell viability and proliferation were investigated. Although Tl stopped cell proliferation, the viability was > 95%. After 3 h, two autophagy markers (SQSTM-1 expression and LC3β localization) were altered, and at 48 h increased expression of SQSTM-1 (60%) and beclin-1 (50-100%) were found. At 24 h, the expression of endoplasmic reticulum (ER) stress markers ATF-6 and IRE-1 were increased in 100% and 150%, respectively, accompanied by XBP-1 splicing and nuclear translocation. At 48 h, major ultrastructure abnormalities were found, including ER enlargement and cytoplasmic vacuolation which was not prevented by protein synthesis inhibition. Increased PHB (85% and 40% for Tl(I) and Tl(III), respectively) and decreased β-tubulin (45%) expression were found which may be related to the promotion of paraptosis. In summary, Tl(I) and Tl(III) promoted ER stress and probably paraptosis in MDCK cells, impairing their proliferation.


Facial Expressions and the Ability to Recognize Emotions from the Eyes or Mouth: A Comparison Between Children and Adults.
The authors sought to contribute to the literature on the ability to recognize anger, happiness, fear, surprise, sadness, disgust, and neutral emotions from facial information. They aimed to investigate if-regardless of age-this pattern changes. More specifically, the present study aimed to compare the difference between the performance of adults and 6- to 7-year-old children in detecting emotions from the whole face and a specific face region, namely the eyes and mouth. The findings seem to indicate that, for both groups, recognizing disgust, happiness, and surprise is facilitated when pictures represent the whole face. However, with regard to a specific region, a prevalence for children was not found between the eyes and mouth. Meanwhile, for adults, would seem to detect a greater role of the eye region. Finally, regarding the differences in the performance of emotions recognition, adults are better only in a few cases, whereas children are better in recognizing anger from the mouth.


Insights on Spirocerca lupi, the Carcinogenic Dog Nematode.
Spirocerca lupi is a nematode transmitted by dung beetles that infects domestic and wild canids in tropical and subtropical regions and is associated with neoplasia. It produces a distinctive pathology with the formation of esophageal nodules classified as inflammatory, preneoplastic, or neoplastic with metastasis to distant organs. Aberrant central nervous system migration of this nematode is also responsible for severe neurological manifestations. Reports of spirocercosis have increased over the last two decades showing spread of this canine helminth in five continents. S. lupi from different geographical locations is genetically distinct with two genotypes, genotype I from Africa, Asia, and Australia, and genotype II from Europe, and recently separated from Spirocerca vulpis, a new species described in red foxes from Europe.


Accelerating Fe2+/Fe3+ cycle via biochar to improve catalytic degradation efficiency of the Fe3+/persulfate oxidation.
The sluggish Fe3+/Fe2+ cycle was the rate-limiting step in the Fenton-like reaction, and metal-free carbonaceous materials are considered as emerging alternatives to solve this problem. However, the effect of carbon material properties on the distribution of reactive species remains poorly understood. This study investigated the possibility and mechanism of using biochar to accelerate the Fe3+/Fe2+ cycle to overcome the low efficiency of Fe3+/persulfate (PS) catalytic oxidation of phenanthrene. More importantly, the contribution of reactive species in the reaction systems with the variation of biochar pyrolysis temperatures was quantitatively studied. The results showed that medium-temperature derived biochar (BC500) had the greatest ability to enhance the Fenton-like system compared to the low- and high-temperature (BC350/700), and the first-order rate constant achieved 5.2 and 35.7-fold increase against the biochar/PS and Fe3+/PS systems, respectively. Using electrochemical evidence, sulfoxide probe tests, and steady-state concentration calculations, radicals yields were found to rise and then reduce with decreasing pyrolysis temperature, while the nonradical contribution of Fe(IV) increased to 56.3%. Electron paramagnetic resonance, Boehm titration, and Raman spectroscopy unraveled that the enhanced effect of biochar resulted from itself persistent free radicals, phenolic-OH, and edge defects, which enabled electron transfer between Fe3+ and biochar. Fe2+ was thus continuously generated and effectively activated the PS. This work enables a better understanding of the Fe3+-mediated Fenton-like reaction in the presence of biochar and provides a sustainable green strategy for Fenton chemistry with potential applications.


Catalytic activity of lignin peroxidase and partition of veratryl alcohol in AOT/isooctane/toluene/water reverse micelles.
The activity of lignin peroxidase (LiP) and the partition of its optimum substrate veratryl alcohol (VA) in sodium bis(2-ethylhexyl)sulfosuccinate (AOT)/isooctane/toluene/water reverse micelles were studied in this paper to understand the microheterogeneous effect of the medium on the catalytic properties of LiP hosted in the reverse micelle. Results showed that LiP from Phanerochaete chrysosporium could express its activity in the reverse micelles, but its activity depended, to a great extent, on the composition of the reverse micelles. Optimum activity occurred at a molar ratio of water to AOT (omega0) of 11, a pH value of 3.6, and a volume ratio of isooctane to toluene of 7-9. Under optimum conditions, the half-life of LiP was circa 12 h. The dependence of LiP activity on the volume fraction of water in the medium (theta), at a constant omega0 value of 11, indicated that VA was mainly solubilized in the pseudophase of the reverse micelle. Based on the pseudobiphasic model and the corresponding kinetic method, a linear line can be obtained in a plot of apparent Michaelis constant of VA vs theta, and the partition coefficient of VA between the pseudophase and the organic solvent phase was determined to be 35.8, which was higher than that (22.3) between bulk water and the corresponding mixed organic solvent. H2O2 inhibited LiP at concentrations higher than 80 microM; this concentration value seems to be different from that in aqueous solution (about 3 mM). The differences mentioned above should be ascribed to the microheterogeneity and the interface of the AOT reverse micelle.