Cationic antimicrobial peptides in penaeid shrimp.
Penaeid shrimp aquaculture has been consistently affected worldwide by devastating diseases that cause a severe loss in production. To fight a variety of harmful microbes in the surrounding environment, particularly at high densities (of which intensive farming represents an extreme example), shrimps have evolved and use a diverse array of antimicrobial peptides (AMPs) as part of an important first-line response of the host defense system. Cationic AMPs in penaeid shrimps composed of penaeidins, crustins, and anti-lipopolysaccharide factors are comprised of multiple classes or isoforms and possess antibacterial and antifungal activities against different strains of bacteria and fungi. Shrimp AMPs are primarily expressed in circulating hemocytes, which is the main site of the immune response, and hemocytes expressing AMPs probably migrate to infection sites to fight against pathogen invasion. Indeed, most AMPs are produced as early as the nauplii developmental stage to protect shrimp larvae from infections. In this review, we discuss the sequence diversity, expression, gene structure, and antimicrobial activities of cationic AMPs in penaeid shrimps. The information available on antimicrobial activities indicates that these shrimp AMPs have potential therapeutic applications in the control of disease problems in aquaculture.


National road casualties and economic development.
This paper explores why traffic fatalities increase with GDP per capita in lower income countries and decrease with GDP per capita in wealthy countries. Data from 41 countries for the period 1992-1996 were obtained on road transport crashes, injuries, and fatalities as well as numbers of vehicles, kilometers of roadway, oil consumption, population, and GDP. Fixed effects regression was used to control for unobservable heterogeneity among countries. A 10% increase in GDP in a lower income country (GDP/Capita <1600) is expected to raise the number of crashes by 7.9%, the number of traffic injuries by 4.7%, and the number of deaths by 3.1% through a mechanism that is independent of population size, vehicle counts, oil use, and roadway availability. Increases in GDP in richer countries appear to reduce the number of traffic deaths, but do not reduce the number of crashes or injuries, all else equal. Greater petrol use and alcohol use are related to more traffic fatalities in rich countries, all else equal. In lower income countries a rise in traffic-related crashes, injuries, and deaths accompanies economic growth. At a threshold of around 1,500 dollars-8,000 dollars per capita economic growth no longer leads to additional traffic deaths, although crashes and traffic injuries continue to increase with growth. The negative association between GDP and traffic deaths in rich countries may be mediated by lower injury severity and post-injury ambulance transport and medical care.


Helicobacter pylori and enteric parasites co-infection among diarrheic and non-diarrheic Egyptian children: seasonality, estimated risks, and predictive factors.
Helicobacter pylori (H. pylori) and intestinal parasites are known for their high prevalence in children. Both of them infect the gastrointestinal tract with overlapping clinical pictures. This study was conducted to determine H. pylori prevalence and its association with intestinal parasites in children, moreover to estimate risk and predictive factors for their detection in stool samples. Single fecal samples were collected from 226 Egyptian pediatric patients (125 diarrheic and 101 non-diarrheic) attending gastroenterology outpatients' clinics, from February 2016 to June 2017. All stool specimens were microscopically examined to search for ova and parasites. Copro-DNAs detection of H. pylori and Cryptosporidium were performed using nested-PCR assays. H. pylori was detected molecularly in 36.8% of the total study population, with a higher prevalence in diarrheic than in non-diarrheic children. Intestinal parasites were detected in 27.4% of the total study populations, of these, 43.9% had co-existence with H. pylori colonized patients and was significantly associated with Cryptosporidium spp. and G. intestinalis. Estimated risk of the presence of H. pylori was in January. Our data provide a better understanding of the epidemiology of H. pylori infection when associated with intestinal parasites. H. pylori co-existence with G. intestinals and Cryptosporidium may suggest the association of H. pylori infection with markers of fecal exposure. Whether H. pylori provides favorable conditions for intestinal parasitosis or vice versa, still further investigations are needed with an emphasis upon determining correlation with gut microbiomes.


Insights into the Melipona scutellaris (Hymenoptera, Apidae, Meliponini) fat body transcriptome.
The insect fat body is a multifunctional organ analogous to the vertebrate liver. The fat body is involved in the metabolism of juvenile hormone, regulation of environmental stress, production of immunity regulator-like proteins in cells and protein storage. However, very little is known about the molecular mechanisms involved in fat body physiology in stingless bees. In this study, we analyzed the transcriptome of the fat body from the stingless bee Melipona scutellaris. In silico analysis of a set of cDNA library sequences yielded 1728 expressed sequence tags (ESTs) and 997 high-quality sequences that were assembled into 29 contigs and 117 singlets. The BLAST X tool showed that 86% of the ESTs shared similarity with Apis mellifera (honeybee) genes. The M. scutellaris fat body ESTs encoded proteins with roles in numerous physiological processes, including anti-oxidation, phosphorylation, metabolism, detoxification, transmembrane transport, intracellular transport, cell proliferation, protein hydrolysis and protein synthesis. This is the first report to describe a transcriptomic analysis of specific organs of M. scutellaris. Our findings provide new insights into the physiological role of the fat body in stingless bees.


[A few insights into the history of the correspondence between Freud and Ferenczi. "The intrications of the different couches"].
The author has given an account of the history of these documents, as from the step taken in 1948 by Ferenczi's widow Gizella who was living in Berne at that time and who contacted Anna Freud in the aim of obtaining the letters addressed by her husband to Freud. One step followed another, and after a number of circuitous moves and hesitations, and, as Michael Balint remarked upon, an intrication of "a different couches", all the protagonists encountered the obstacle of a reticence working to protect the private lives of people still living ... Today, after the formation of a committee for the publication of these 1,300 letters which constitute a veritable human and psychological treasure trove, the psychological and legal barriers surrounding their publication seem to have been done away with and, financial backing having been found, the moment when these valuable documents will be published appears to be near.


Dynamic complexity in the electrochemical oxidation of thiourea.
We explored the temperature-dependent dynamics of the electrochemical oxidation of thiourea under potential-control mode and found complex oscillations with one large peak and one small peak per period. Adjusting the temperature caused the relative amplitudes and positions of the two peaks to vary. Experiments showed that there were two distinct oscillatory regimes as a function of the external current, and at some temperatures, three-frequency quasiperiodic oscillations occurred for current densities between the two oscillatory windows. We examined the species present and the component reactions by employing cyclic voltammetry and electrolysis-HPLC-MS in the two oscillatory regimes. Adsorption and desorption of multiple species, including water and chloride, contribute to the rich dynamical phenomena that were observed.


Insights into the Mechanisms and Structure of Breakage-Fusion-Bridge Cycles in Cervical Cancer using Long-Read Sequencing.
Cervical cancer is caused by human papillomavirus (HPV) infection, has few approved targeted therapeutics, and is the most common cause of cancer death in low-resource countries. We characterized 19 cervical and four head and neck cell lines using long-read DNA and RNA sequencing and identified the HPV types, HPV integration sites, chromosomal alterations, and cancer driver mutations. Structural variation analysis revealed telomeric deletions associated with DNA inversions resulting from breakage-fusion-bridge (BFB) cycles. BFB is a common mechanism of chromosomal alterations in cancer, and this is one of the first analyses of these events using long-read sequencing. Analysis of the inversion sites revealed staggered ends consistent with exonuclease digestion of the DNA after breakage. Some BFB events are complex, involving inter- or intra-chromosomal insertions or rearrangements. None of the BFB breakpoints had telomere sequences added to resolve the dicentric chromosomes and only one BFB breakpoint showed chromothripsis. Five cell lines have a Chr11q BFB event, with YAP1/BIRC2/BIRC3 gene amplification. Indeed, YAP1 amplification is associated with a 10-year earlier age of diagnosis of cervical cancer and is three times more common in African American women. This suggests that cervical cancer patients with YAP1/BIRC2/BIRC3-amplification, especially those of African American ancestry, might benefit from targeted therapy. In summary, we uncovered new insights into the mechanisms and consequences of BFB cycles in cervical cancer using long-read sequencing.


Beneficial effects of treadmill training in a cerebral palsy-like rodent model: walking pattern and soleus quantitative histology.
The aim of the present study was to investigate whether treadmill locomotor training could have beneficial effects on deficits consequent to perinatal anoxia, sensorimotor restriction or a combination of both. Fifty-six newborn male Wistar rats were divided into four groups: control, anoxic, sensorimotor-restricted and anoxic-sensorimotor-restricted. Rats were exposed to anoxia in the first two postnatal days (P0 and P1) and/or hind-limb sensorimotor restriction from P2 to P28 for 16 h/day. Control and experimental rats underwent treadmill training for three weeks (from P31 to P52). Body weight and walking patterns (stride length and foot angle) were measured weekly during treadmill locomotor training. Soleus muscle cross-sectional mean area and fiber density were measured using planar morphometry. Anoxia per se did not cause gait or muscle deficits. Body weight, stride length and soleus fiber cross-sectional mean area, however, were increased in trained anoxic rats. Sensorimotor-restricted animals, either with or without perinatal anoxia, showed deficits in body weight gain, decreased stride length, wider foot angle and soleus fiber atrophy. In the sensorimotor-restricted group, treadmill training improved body weight gain and stride length, and decreased the percentage of the atrophic fibers. However, in the anoxic-sensorimotor-restricted group, training improved stride length only. Three weeks of treadmill training were able to improve stride length in restricted and anoxic-restricted animals, although body weight deficit and the degree of degradation in muscle histology were reduced only in the restricted group.


An evaluation of the impact of the ventilator care bundle.
A number of interventions have been shown to improve the outcomes of patients who are invasively ventilated in intensive care units (ICUs). However, significant problems still exist in implementing research findings into clinical practice. The aim of this study was to assess whether the systematic and methodical implementation of evidence-based interventions encapsulated in a care bundle influenced length of ventilation and ICU length of stay (LOS). A ventilator care bundle was introduced within a general ICU and evaluated 1 year later. The care bundle was composed of four protocols that consisted of prophylaxis against peptic ulceration, prophylaxis against deep vein thrombosis, daily cessation of sedation and elevation of the patient's head and chest to at least 30 degrees to the horizontal. Compliance with the bundle was assessed, as was ICU LOS, ICU mortality and ICU/high-dependency unit patient throughput. Mean ICU LOS was reduced from 13-75 [standard deviation (SD) 19.11] days to 8.36 (SD 10.21) days (p<0.05). Mean ventilator days were reduced from 10.8 (SD 15.58) days to 6.1 (SD 8.88) days. Unit patient throughput increased by 30.1% and the number of invasively ventilated patients increased by 39.5%. Care bundles encourage the consistent and systematic application of evidence-based protocols used in particular treatment regimes. Since the introduction of the ventilator care bundle, length of ventilation and ICU LOS have reduced significantly.


Temperature-related deaths in people with psychosis, dementia and substance misuse.
Climate change is expected to have significant effects on human health, partly through an increase in extreme events such as heatwaves. People with mental illness may be at particular risk. To estimate risk conferred by high ambient temperature on patients with psychosis, dementia and substance misuse. We applied time-series regression analysis to data from a nationally representative primary care cohort study. Relative risk of death per 1°C increase in temperature was calculated above a threshold. Patients with mental illness showed an overall increase in risk of death of 4.9% (95% CI 2.0-7.8) per 1°C increase in temperature above the 93rd percentile of the annual temperature distribution. Younger patients and those with a primary diagnosis of substance misuse demonstrated greatest mortality risk. The increased risk of death during hot weather in patients with psychosis, dementia and substance misuse has implications for public health strategies during heatwaves.


Thiourea modulates the expression and activity profile of mtATPase under salinity stress in seeds of Brassica juncea.
Large areas of the globe are becoming saline due to evapotranspiration and poor irrigation practices, and sustainability of agriculture is being seriously affected. Thiourea (TU) has been identified as an effective bioregulator imparting stress tolerance to crops. The molecular mechanisms involved in the TU-mediated response are considered in this study. Differential display was performed in order to identify TU-modulated transcripts in Brassica juncea seeds exposed to various treatments (distilled water; 1 m NaCl; 1 m NaCl + 500 p.p.m. TU). The differential regulation of these transcripts was validated by quantitative real-time PCR. Thiourea treatment maintained the viability of seeds exposed to NaCl for 6 h. Expression analysis showed that the transcript level of alpha, beta, gamma, delta and epsilon subunits of mitochondrial ATPase (mtATPase) varied in seeds subjected to the different treatments for 1 h: expression level was significantly altered by 1 m NaCl relative to controls; however, in the NaCl + TU treatment it reverted back in an integrated manner. Similar results were obtained from time-kinetics studies of beta and delta subunits in roots of 8-d-old seedlings. These observations were also confirmed by the mtATPase activity from isolated mitochondria. The reversal in the expression and activity profile of mtATPase through the application of a bioregulator such as TU is a novel finding for any plant system. The results suggest that TU treatment maintains the integrity and functioning of mitochondria in seeds as well as seedlings exposed to salinity. Thus, TU has the potential to be used as an effective bioregulator to impart salinity tolerance under field conditions, and might prove to be of high economic importance by opening new avenues for both basic and applied research.


Spectrum of anemia in pregnant Indian women and importance of antenatal screening.
Anemia is a common health problem but control of anemia in pregnant women is less well studied. The purpose was to study prevalence of anemia in young pregnant women, correlate with indices and study significance of identification of hemoglobinopathies. Of the 120 pregnant women, Hb was less than 8 g% in 58 (44.2%). Seventy-eight (65%) had iron deficiency, 22 (18.3%) had dimorphic anemia, and 14 (11.6%) had hemolytic anemia. Megaloblastic anemia was present in 6 (5%). Of hemolytic anemia, 50% were thalassemia trait. MCV< 76 fl was observed in 88 (73.3 %) cases. MCV<76 fl and MCH < 27 pg had 100 % sensitivity and 28.7 % specificity for screening of beta-thalassemia trait. NESTROFT had comparable sensitivity but lower specificity (14.9%). Sixty-three percent (60/78) of IDA had increased RDW whereas 78 % (11/14) of hemolytic anemia had RDW value in normal range (p value< 0.05). MCV/RBC of <14 was more specific parameter (96.8%) for beta-thalassemia trait. Four high-risk couples were identified. Thus, moderate to severe anemia was observed in most pregnant women. Hemoglobinopathies should be screened in antenatal clinics to identify the couples that would need a prenatal test. A lower MCV/RBC with RDWin the normal range may be useful in screening for thalassemia trait in pregnant women.


Specimen acquisition training with a new biosimulator in endobronchial ultrasound-guided transbronchial needle aspiration.
Training for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has focused on the procedure itself; however, the techniques for obtaining adequate sample are also important for achieving a pathological diagnosis as well as for molecular testing. The aim of this study was to evaluate the feasibility and efficacy of a biosimulator for training subjects in adequate sample acquisition during EBUS-TBNA.A total of 19 bronchoscopists voluntarily participated in this study. A biosimulator (ArtiCHEST, HARADA Corporation, Tokyo, Japan) was used for the training. After a 10-minute briefing, the first pass was performed by pairs of trainees. The trainees then received a 30-minute lecture that focused on the acquisition of samples using EBUS-TBNA. The trainees next performed their second pass under the supervision of the trainers. Each participant obtained a cytological smear that was coded and evaluated for quantity as well as quality by an independent cytotechnologist.The trainees had an average of 5.9 years of bronchoscopy experience. With regard to the quantity evaluation, 9 (47.4%) subjects sampled a greater number of lymphocytes on the second pass than on the first, whereas 2 were better on the first pass, and the others sampled roughly the same amount both times. With regard to the quality assessment, 9 (47.4%) subjects obtained better quality samples on the second pass, whereas the quality of the first and second pass was deemed to be roughly the same for the remaining subjects.A biosimulator can be used to train doctors in specimen acquisition and evaluate their skills with sampling using EBUS-TBNA.


Zero-field dichroism in the solar chromosphere.
We explain the linear polarization of the Ca ii infrared triplet observed close to the edge of the solar disk. In particular, we demonstrate that the physical origin of the enigmatic polarizations of the 866.2 and 854.2 nm lines lies in the existence of atomic polarization in their metastable (2)D(3)(/2, 5/2) lower levels, which produces differential absorption of polarization components (dichroism). To this end, we have solved the problem of the generation and transfer of polarized radiation by taking fully into account all the relevant optical pumping mechanisms in multilevel atomic models. We argue that "zero-field" dichroism may be of great diagnostic value in astrophysics.


Periodontal disease in cats: back to basics--with an eye on the future.
Periodontal disease is commonly encountered in feline practice. Gingivitis, followed by inflammation of the rest of the periodontal tissues, can lead to chronic oral infection, bacteraemia, pain and ultimately tooth loss. Given adequate plaque control and thorough, consistent dental home care, gingivitis is a reversible and controllable condition. Periodontitis, however, is an essentially irreversible and progressive condition. Treatment aims to control tissue inflammation, returning the gingiva to clinical health and preventing destruction of the periodontium in other parts of the mouth. Diagnosis must be established using a combination of oral examination under anaesthesia and dental radiography. Periodontitis leads to tooth attachment loss, and given the short length of most cat teeth, probing depths of 1 mm or more should alert the clinician to the presence of periodontitis. The decision of whether to extract or preserve affected teeth needs careful consideration. In practice, as periodontitis is often associated with type 1 tooth resorption, extraction is often required, but the slender and delicate nature of feline tooth roots, compounded by the destructive nature of tooth resorption, can frustrate extraction attempts. As highlighted in this article, iatrogenic damage to teeth is also a real risk if periodontal therapy procedures (including scaling and polishing) are not performed carefully. The challenges of providing home care in the cat are additionally discussed. The authors have drawn upon, wherever possible, an evidence base relating strictly to the feline patient. Where there is a lack of published research, evidence from canine and human studies is assessed.


Attraction of Chrysotropia ciliata (Neuroptera, Chrysopidae) Males to P-Anisaldehyde, a Compound with Presumed Pheromone Function.
In a field-trapping experiment with plant volatiles, we observed notably high attraction of green lacewing (Chrysotropia ciliata) males to the compound p-anisaldehyde. Based on this finding, we initiated the present study to elucidate this phenomenon and to investigate the chemical ecology of C. ciliata. Scanning electron microscopy revealed elliptical glands abundantly distributed on the 2nd to 6th abdominal sternites of C. ciliata males, whereas females of the species completely lacked such glands. No p-anisaldehyde was found in extractions of body parts of C. ciliata. Methyl p-anisate and p-methoxybenzoic acid were identified exclusively in the extract from abdominal segments 2-8 of males. Field-trapping experiments revealed no attraction of C. ciliata to either methyl p-anisate or p-methoxybenzoic acid. In contrast, males showed marked attraction to p-anisaldehyde in the field and antennae showed strong responses to this compound. Headspace collections in the field from living insects in their natural environment and during their main daily activity period indicated that p-anisaldehyde was emitted exclusively by C. ciliata males. Our overall results suggest that p-anisaldehyde might serve as a male-produced pheromone that attracts conspecific C. ciliata males. Here, we discuss hypotheses regarding possible mechanisms involved in regulation of p-anisaldehyde production, including involvement of the compounds methyl p-anisate and p-methoxybenzoic acid, and the potential ecological function of p-anisaldehyde in C. ciliata.


Impact of benralizumab on asthma exacerbation-related medical healthcare resource utilization and medical costs: results from the ZEPHYR 2 study.
Benralizumab is a biologic add-on treatment for severe eosinophilic asthma that can reduce the rate of asthma exacerbations, but data on the associated medical utilization are scarce. This retrospective study evaluated the economic value of benralizumab by analyzing healthcare resource utilization (HRU) and medical costs in a large patient population in the US. Insurance claims data (11/2016-6/2020) were analyzed. A pre-post design was used to compare asthma exacerbation rates, medical HRU and medical costs in the 12 months pre vs. post index (day after benralizumab initiation). Patients were aged ≥12 years, with ≥2 records of benralizumab and ≥2 asthma exacerbations pre index, and constituted non-mutually exclusive cohorts: biologic-naïve, biologic-experienced (switched from omalizumab or mepolizumab to benralizumab), or with extended follow-up (18 or 24 months). In all cohorts (mean age 51-53 years; 67-70% female; biologic-naïve, N = 1,292; biologic-experienced, N = 349; 18-month follow-up, N = 419; 24-month follow-up, N = 156), benralizumab treatment reduced the rate of asthma exacerbation by 53-68% (p < .001). In the biologic-naïve cohort, inpatient admissions decreased by 58%, emergency department visits by 54%, and outpatient visits by 58% post index (all p < .001), with similar reductions in exacerbation-related medical HRU in other cohorts. Exacerbation-related mean total medical costs decreased by 51% in the biologic-naïve cohort ($4691 pre-index, $2289 post-index), with cost differences ranging from 16% to 64% across other cohorts (prior omalizumab: $2686 to $1600; prior mepolizumab: $5990 to $5008; 18-month: $3636 to $1667; 24-month: $4014 to $1449; all p < .001). Medical HRU and cost reductions were durable, decreasing by 64% in year 1 and 66% in year 2 in the 24 month follow-up cohort. Patients treated with benralizumab with prior exacerbations experienced reductions in asthma exacerbations and exacerbation-related medical HRU and medical costs regardless of prior biologic use, with the benefits observed for up to 24 months after treatment initiation.


The Impact of Physical Activity and Inactivity on Cardiovascular Risk across Women's Lifespan: An Updated Review.
Physical inactivity (PI) represents a significant, modifiable risk factor that is more frequent and severe in the female population worldwide for all age groups. The physical activity (PA) gender gap begins early in life and leads to considerable short-term and long-term adverse effects on health outcomes, especially cardiovascular (CV) health. Our review aims to highlight the prevalence and mechanisms of PI across women's lifespan, describing the beneficial effects of PA in many physiological and pathological clinical scenarios and underlining the need for more awareness and global commitment to promote strategies to bridge the PA gender gap and limit PI in current and future female generations.


Visible-Light Responsive Sucrose-Containing Macrocyclic Host for Cations.
Chiral photoresponsive host 1 was prepared by a high-yield Cs2CO3-templated macrocyclization. Trans-1 transforms into long-lived cis-1 (25 days) upon irradiation with green light, and the backward transformation is triggered by blue light. Both isomers prefer potassium among alkali metal cations, and cis-1 binds cations stronger than trans-1 (Kcis/Ktrans ≤ 4.1). 1H NMR titration experiments as well as density functional theory studies reveal that sucrose ring oxygen residues and azobenzene nitrogen atoms in 1 contribute to cation coordination.


The GABAA/benzodiazepine receptor is a heterotetramer of homologous alpha and beta subunits.
The GABAA receptor has been purified to homogeneity from bovine cerebral cortex. Under stringent conditions of isolation, the GABAA receptor was shown to consist only of alpha (Mr 53 000) and beta (Mr 57 000) subunits. A densitometric scan of SDS-PAGE gels under reducing conditions showed that these subunits were present in a 1:1 ratio. A model of the receptor as a heterologous tetramer alpha 2 beta 2 is proposed. Monoclonal antibodies have been raised to the purified bovine GABAA receptor. One of these antibodies, 1A6, was shown to react with both the alpha and beta subunits of the purified receptor. The subunits were still positive in immunoblots following the removal of the carbohydrate moieties of the respective polypeptides by endoglycosidase F treatment. This antibody has been employed to demonstrate antigenic cross-reactivity between the GABAA receptors of three vertebrate species. It is further proposed that there is partial amino acid sequence homology between the alpha and beta polypeptides and hence that they are derived from a single ancestral gene.


Scale locality of magnetohydrodynamic turbulence.
We investigate the scale locality of cascades of conserved invariants at high kinetic and magnetic Reynold's numbers in the "inertial-inductive range" of magnetohydrodynamic (MHD) turbulence, where velocity and magnetic field increments exhibit suitable power-law scaling. We prove that fluxes of total energy and cross helicity-or, equivalently, fluxes of Elsässer energies-are dominated by the contributions of local triads. Flux of magnetic helicity may be dominated by nonlocal triads. The magnetic stretching term may also be dominated by nonlocal triads, but we prove that it can convert energy only between velocity and magnetic modes at comparable scales. We explain the disagreement with numerical studies that have claimed conversion nonlocally between disparate scales. We present supporting data from a 1024{3} simulation of forced MHD turbulence.


Ventricular ectopic activity during myocardial ischemic episodes in ambulatory patients.
The association between ventricular ectopic activity (VEA) and ischemic episodes during everyday activities was investigated in ambulatory patients with stable angina pectoris. Seventy-five consecutive patients with proven coronary artery disease, ischemic episodes on Holter monitoring and positive treadmill tests, but without known ventricular arrhythmias, were prospectively studied. In these 75 patients, a total of 719 ischemic episodes were recorded during 127 twenty-four-hour monitoring periods. Forty-three patients had either no or only very low baseline VEA (less than 14 ventricular premature complexes [VPCs]/24 hours); none of these patients had increased VEA during any ischemic episode. However, among 32 patients who had greater than or equal to 14 VPCs/24 hours (average 243 VPCs/24 hours), increased VEA during ischemic episodes was observed in 11 (31%). These 11 patients had a total of 174 ischemic episodes and the increased VEA appeared in 47 (27%) of the episodes. During 40 of the ischemic episodes the number of single VPCs increased significantly compared to the baseline background VEA: during 4 episodes trigeminy appeared and during another 3 bigeminy was observed. More complex VEA was not observed. Among the 11 patients with increased VEA, only 4 developed VPCs during treadmill testing. No correlation was found between the severity of the ischemic episodes (degree of ST depression and duration of ischemia) and the increased VEA. In 83% of these episodes the increased VEA appeared during the last (possibly reperfusion) phase. No correlation was found between the appearance of ventricular arrhythmias during ischemic episodes and the presence or absence of chest pain at the same time.(ABSTRACT TRUNCATED AT 250 WORDS)


Prophylaxis against and promotion of organophosphate-induced delayed neuropathy by phenyl di-n-pentylphosphinate.
Phenyl di-n-pentylphosphinate (PPP) is a potent inhibitor of neuropathy target esterase (NTE) with negligible effect on acetylcholinesterase: I50S at 37 degrees C for 20 min and pH 8, respectively are 0.2 microM and > 2mM. PPP is not neuropathic. This is compatible with the fact that inhibited NTE is autopsy material from hens dosed with PPP can always be reactivated in vitro, presumably because no 'aging' reaction has occurred. PPP (10 mg/kg s.c.) given to hens up to 4 days before severely neuropathic doses (1.7 mg/kg) of diisopropylphosphorofluoridate (DFP) prevented neuropathic but not cholinergic effects of DFP. Hens given PPP 3 days after a sub-neuropathic dose of DFP (0.4 mg/kg) developed severe clinical neuropathy (clinical scores of 7 and 5 compared with DFP-plus-solvent scores 0,1,3). These prophylactic and promoting effects are similar to those exerted by phenylmethanesulphonyl fluoride (PMSF) at doses which inhibit NTE. In 3 out of 4 birds a pre-dose with PMSF (15 mg/kg) prevented the promoting effect of 120 mg/kg PMSF given after DFP.


Inpatient management of gamma-hydroxybutyrate withdrawal.
To describe the baseline characteristics, treatment and retention in patients electively admitted for gamma-hydroxybutyrate (GHB) withdrawal management. All patients admitted between July 2010 to June 2016 who used GHB two or more times per week with a minimum duration of 3 months were identified and data extracted by file review. Twelve cases satisfied the inclusion criteria, of whom 50% were female; 75% were using GHB daily, with an average daily amount of 16 ml. Average duration of use was 60 months. All subjects were using amphetamine type stimulants and nicotine. Psychiatric comorbidity and unintentional overdose were common; 50% completed treatment. Medications used included diazepam and neuroleptic. Two patients completed withdrawal with no medications. No subject using greater than 90 ml GHB in the preceding week completed treatment. Pattern of GHB use did not predict medication requirements during withdrawal management. There were low numbers attending for elective treatment for GHB use. Heavier GHB use predicted poor treatment retention. Polysubstance use and psychiatric co-morbidities need consideration in treatment planning.


[Continuity of care: community care in Italy and Sweden. A comparison].
One of the objectives of the Health 21 document, approved by the World Health Association, European Region, is to create by the year 2010 an integrate sanitary system, where the population of the region count on a better access to the health services aimed at the family and the community. In accordance with the tendencies of the European nation, which are more and more open to confrontation, the research has, as main objective, the parallel analysis of the welfare continuity and integration of the Italian Nursing Home Care Service compared to the Swedish Health Care Service. The research has been structured from a sanitary accreditation project that the Veneto Region has started with the collaboration of the Ottawa Council On Health Services Accreditation (Cchsa). The analysis puts in evidenced the completion of the offer of the territory home services present in Padua. The comparison with the Swedish situation however puts in evidence some gaps and some possible developments of the Italian service involving above all the complete transcription of the patient information and the continuity of its communication, in particular in the nursing field. Another possible development of the Italian service concerns the method continuity, between the working units themselves and with the territory, which could be achieved using common nursing guide lines and protocols to manage standard caring situations. From the analysis of the european services it results that it is the nurse who has the most relevant role for the care quality improvement.


Processing of subliminal facial expressions of emotion: a behavioral and fMRI study.
The recognition of emotional facial expressions is an important means to adjust behavior in social interactions. As facial expressions widely differ in their duration and degree of expressiveness, they often manifest with short and transient expressions below the level of awareness. In this combined behavioral and fMRI study, we aimed at examining whether or not consciously accessible (subliminal) emotional facial expressions influence empathic judgments and which brain activations are related to it. We hypothesized that subliminal facial expressions of emotions masked with neutral expressions of the same faces induce an empathic processing similar to consciously accessible (supraliminal) facial expressions. Our behavioral data in 23 healthy subjects showed that subliminal emotional facial expressions of 40 ms duration affect the judgments of the subsequent neutral facial expressions. In the fMRI study in 12 healthy subjects it was found that both, supra- and subliminal emotional facial expressions shared a widespread network of brain areas including the fusiform gyrus, the temporo-parietal junction, and the inferior, dorsolateral, and medial frontal cortex. Compared with subliminal facial expressions, supraliminal facial expressions led to a greater activation of left occipital and fusiform face areas. We conclude that masked subliminal emotional information is suited to trigger processing in brain areas which have been implicated in empathy and, thereby in social encounters.


HIV-testing behavior and associated factors among MSM in Chongqing, China: results of 2 consecutive cross-sectional surveys from 2009 to 2010.
The high and climbing human immunodeficiency virus (HIV) rates among Chinese men who have sex with men (MSM) bring huge pressure and challenge to acquired immune deficiency syndrome response work in China. This study examined HIV-testing behavior and describes the characteristics of recently tested MSM in Chongqing to address targeting HIV prevention interventions. Two consecutive cross-sectional surveys were conducted among Chongqing MSM using respondent-driven sampling in 2009 and 2010. Information was collected regarding details on demographic characteristics, sexual practices with male and female partners, and HIV-testing experiences. Univariate and multivariate logistic regression analyses were performed to identify factors independently associated with recent HIV testing.The final sample size included in our analyses was 992. The overall HIV prevalence was 13.4%, and HIV prevalence increased significantly from 11.6% in 2009 to 15.4% in 2010 (P = 0.08). The overall rate of HIV testing in the past 12 months was 44.6%, and the self-reported rates decreased significantly from 47.8% in 2009 to 41.1% in 2010 (P = 0.03). Factors independently associated with recent HIV testing included living in Chongqing >1 year (adjusted odds ratio [AOR] 1.8, 95% confidence interval [CI] 1.1-2.9), the age of most recent male partner ≤ 25 (AOR 1.5, 95% CI 1.1-2.1), not having unprotected insertive anal sex with most recent male partner in the past 6 months (AOR 1.5, 95% CI 1.1-2.0), disclosing HIV status to most recent male partner (AOR 2.8, 95% CI 2.0-3.8), and holding lower level of HIV-related stigma (AOR 1.1 per scale point, 95% CI 1.0-1.1). The extremely high HIV prevalence and low annual testing level put MSM at high risk of HIV infection and transmission, and it is a priority to promote regular HIV testing among this group in order to control the spread of HIV in Chongqing, China.


The contribution of one-dimensional motion mechanisms to the perceived direction of drifting plaids and their after effects.
When motion aftereffects (MAEs) are measured by adapting to a drifting plaid (simultaneous adaptation) or by adapting to the plaid's component gratings in alternation (alternating adaptation), it has been shown that the velocity and duration of the MAE are smaller in the latter case [Wenderoth, P., Bray, R. & Johnstone, S. (1988) Perception, 17, 81-91; Burke, D. & Wenderoth, P. (1993) Vision Research, 33, 351-359]. However, Burke and Wenderoth additionally reported that the directions of MAEs induced by simultaneous and alternating adaptation were identical, an apparent inconsistency if the differences in duration and velocity were due to the presence of "blobs" at the component grating intersects in the simultaneous case. Presumably, the direction of the "blobs" should also affect perceived plaid direction during adaptation and, hence, the MAE direction. In five experiments, we have measured both perceived adapting plaid and MAE direction, tested with both alternating and simultaneous adaptation, measured interocular transfer of plaid-induced MAEs and obtained MAE and plaid direction judgments under monocular and binocular viewing conditions. All of the data indicate that there is a blob tracking mechanism which is preferentially stimulated by plaids whose component gratings have high spatial frequency, low temporal frequency and high contrast. Differences between simultaneous and alternating adaptation emerge only when more optimal blobs are used, thus accounting for Burke and Wenderoth's failure to find a difference. The data also support Burke and Wenderoth's claim that the blob tracking mechanism is monocular: alternating and simultaneous adaptation produce identical MAEs under interocular transfer conditions, even using plaids with more optimal blobs. We also report the unexpected finding that plaids with more- and less-optimal blobs appear to drift in directions 20 degrees apart yet their aftereffects differ in direction by only 3-5 degrees. That is, more optimal blob plaids--compared with less optimal blob plaids--change both perceived plaid direction during adaptation and subsequent perceived MAE direction but the latter change is much more modest. Possible explanations of this dissociation are considered.


Successful Treatment of Cutaneous Leishmaniasis With Cryotherapy.
Leishmaniasis, a protozoal infection, is a growing health concern with 1.5 million new cases reported annually resulting in a wide spectrum of disease and clinical presentations. The disease is endemic in 98 countries with increasing prevalence in non-endemic areas. There are various treatment approaches that are often individualized based on host and parasite factors. Current treatment guidelines and data are variable and provide limited direction for specific treatment plans. Additionally, current recommended therapies are not benign, and are expensive and unavailable to most patients, especially in low-resource areas where leishmaniasis is most prevalent. Here, we report the diagnosis and successful treatment of cutaneous leishmaniasis in a 65-year-old male, who recently traveled to Mexico. Initial treatment with topical antifungals and oral antibiotics was ineffective. After successive treatment with local liquid nitrogen, the lesions completely resolved with no adverse effects or recurrence. Given there is limited evidence-based data supporting cryotherapy treatment as a first-line treatment, this report supports the efficacy of cryotherapy as a safe, cost-effective, and accessible treatment for cutaneous leishmaniasis.


HLA class I and class II association with ankylosing spondylitis in a southern Indian population.
Ankylosing spondylitis (AS) is a chronic inflammatory condition associated with HLA B27. But the association is not absolute. Hence association with other HLA class I antigens and class II alleles was studied in a southern Indian population. Sixty-five patients with primary AS were typed serologically for HLA class I antigens. Age- and sex-matched disease controls (37 with enterogenic reactive arthritis [ReA] and 25 with undifferentiated spondyloarthropathy [UnSpA]) and 124 healthy controls were studied. PCR-based DNA-SSO typing for DQA1 and DQB1 was performed on 20 patients with AS and 38 healthy controls. Twenty-three patients with AS and 39 controls were typed for DRB1 alleles. HLA B27 was positive in 76.9 % of the cases of AS (RR 811), 59.5% of those with ReA (RR 9.3), and 40% of the patients with UnSpA (RR 9.3), while none of the controls were B27 positive. The P value for positive association was highly significant for B27 in all the three groups. B27 positivity was associated with earlier age of onset of disease in all the diseases compared to the B27-negative group. HLA Cw2 was positively associated with AS (P highly significant; OR 52) and ReA (P = 0.0003; OR 14.2). HLA A1 and CW6 were significantly negatively associated only with AS (P = 0.0001 and 0.00004 and OR 0.25 and 0.02, respectively). None of the HLA class II alleles were significantly associated with AS. The apparent association with DRB1*11 (P = 0.03) was lost after Yates correction.


Zeolite-silver-zinc nanoparticles: Biocompatibility and their effect on the compressive strength of mineral trioxide aggregate.
This study was carried out to evaluate the biocompatibility of zeolite-silver-zinc (Ze-Ag-Zn) nanoparticles and their effect on the compressive strength of Mineral Trioxide Aggregate (MTA). Biocompatibility was evaluated by an MTT assay on the pulmonary adenocarcinoma cells with 0.05, 0.1, 0.25, 0.5, 1 and 5 mg/mL concentrations of Ze-Ag-Zn. For compressive strength test, four groups containing 15 stainless-steel cylinders with an internal diameter of 4 and a height of 6 mm were prepared and MTA (groups 1 and 2) or MTA + 2% Ze-Ag-Zn (groups 3 and 4) were placed in the cylinders. The compressive strength was evaluated using a universal testing machine 4 days after mixing in groups 1 and 3, and 21 days after mixing in groups 2 and 4. There was no significant difference between cytotoxicity of different concentrations. The highest (52.22±18.92 MPa) and lowest (19.57±5.76 MPa) compressive strength were observed in MTA group after 21 days and in MTA + 2% Ze-Ag-Zn group after four days, respectively. The effect of time and 2% Ze-Ag-Zn on the compressive strength were significant (P<0.05). Mixing MTA with Ze-Ag-Zn significantly reduced and passage of time from day four to 21 significantly increased the compressive strength. Mixing MTA with 2% Ze-Ag-Zn had an adverse effect on the compressive strength of MTA, but this combination had no cytotoxic effects. Key words:Compressive strength, Cytotoxicity, Mineral Trioxide Aggregate, Nanoparticle, Zeolite-Silver-Zinc.


Splanchnic and peripheral vascular resistance during lower body negative pressure (LBNP) and tilt.
We tested the hypothesis that vasoconstriction in response to LBNP or head up tilt would be reflected in a reduction in splanchnic (portal vein) blood flow (PVF) and increases in forearm and total peripheral vascular resistance (TPR). Changes in vascular resistance indicators were obtained from measurement of PVF from portal vein cross-sectional area and blood velocity by Doppler ultrasound, from forearm vascular resistance (FVR, by Doppler) and total peripheral resistance (TPR, by impedance cardiography). 21 subjects were tested during LBNP (0, -10, -20 and -30 mmHg) and 9 subjects during tilt (0, 45 and 70 degrees). During progressive LBNP, PVF decreased approximately linearly with LBNP (-30, -48 and -64% at -10, -20 and -30 mmHg) and with tilt angle (-39 and -58% at 45 and 70 degrees). The increase in FVR approximately mirrored these changes during LBNP (20.1, 44.7 and 55.3%) and tilt (45.6 and 63.6%). However, the changes in TPR during LBNP (12.0, 16.9 and 26.4%) and tilt (25.2 and 29.2%) were markedly less. This observation of different percent changes in forearm versus total peripheral resistance might reflect true physiological differences in the forearm (and splanchnic) circulations compared with the whole body, or the data might suggest that impedance cardiography did not provide a reliable indicator of cardiac output and therefore TPR under these conditions. The primary observation in this study was that Doppler ultrasound measurement of portal vein blood flow provided a non-invasive estimate of splanchnic vascular resistance during postural or LBNP challenge and that using the reduction in portal vein flow as an index of increased vasoconstriction paralleled the change in forearm vascular resistance.


Management of otosclerosis in the UK.
The last 30 years has seen a gradual change in the management of otosclerosis. The aim of this study is to evaluate the current practice among British otolaryngology consultants using a questionnaire, and to compare it with the practice reported in a survey 8 years ago. A total of 353 valid responses (64.5%) were available for analysis. The overall trend is towards centralization, with a reduction in the number of surgeons undertaking stapes surgery (49.9%). The majority of consultants (81.3%) who undertake stapes surgery would operate for a unilateral conductive loss and 75.1% would undertake bilateral stapes surgery. Stapedotomy is the operation of choice (82%), with a few consultants performing partial or rarely total stapedectomies. Postoperative restrictions and follow-up times vary widely amongst surgeons, with the senior surgeons tending to be more conservative than the younger consultants.


Hepatitis C Infection: A Systemic Disease
It is critical to recognize that hepatitis C virus (HCV) infection is, in fact, a multifaceted systemic disease with both hepatic and extrahepatic complications. It is also important to recognize that the comprehensive burden of HCV should include not only its clinical burden but also its burden on the economic and patient-reported outcomes. It is only through this comprehensive approach to HCV infection that we can fully appreciate its true burden and understand the full benefit of curing HCV for the patient and the society.


Gold-induced colitis: a case report and review of the literature.
A case of severe colitis requiring subtotal colectomy following administration of 35 mg Solganal b for intractable arthritis is described. Abdominal pain and watery diarrhea developed six weeks after the last dose of gold. Colonoscopy revealed mucosal edema and ulceration of the entire colon. Supportive measures failed and the patient required subtotal colectomy. Review of the literature revealed 29 cases, ranging in severity from limited ileal involvement to fulminant panenteritis. Most of the patients responded to intravenous fluids, steroids, and antibiotics, but four required surgery. The case described is notable for the delay in appearance of abdominal symptoms following the cessation of gold therapy. The mechanism of injury is unknown. Abdominal complaints in a patient who has received gold therapy, especially parenteral, merit strict attention, even if occurring several weeks after the final dose, and the diagnosis of gold colitis should be entertained.


A 5-year, multicenter, open-label, safety study of adjunctive latanoprost therapy for glaucoma.
To evaluate the 5-year safety and efficacy of adjunctive 0.005% latanoprost once daily. Patients with primary open-angle or exfoliation glaucoma who completed a 3-year, open-label, uncontrolled, prospective trial could enter a 2-year extension phase. High-resolution color photographs of irides were taken at baseline and at 14 subsequent visits. Photographs were assessed for change in iris pigmentation compared with baseline. Intraocular pressures and adverse events were recorded. Development and progression of increased iris pigmentation over 5 years. Of the 519 original patients, 380 enrolled in the extension phase with approximately 89% having an eye color known to be susceptible to color change. After 5 years, most patients had no increase in iris pigmentation, but certain colored irides exhibited notably greater susceptibility than others. For those whose irides did change, onset occurred during the first 8 months in 74% and during the first 24 months in 94%. No patient developed an increase in pigmentation after month 36; the rate of progression decreased over time. Adverse event profiles were similar for patients with and without increased pigmentation. The overall mean intraocular pressure reduction from baseline of 25% was sustained with no need for change in intraocular pressure-lowering treatment in 70% of the eyes. Latanoprost therapy is safe and well tolerated for long-term treatment of open-angle glaucoma.


Ligand-Modified Gold Nanoparticles as Mitochondrial Modulators: Regulation of Intestinal Barrier and Therapy for Constipation.
Intestinal metabolism-related diseases, such as constipation, inflammatory bowel disease, irritable bowel syndrome, and colorectal cancer, could be associated with the dysfunction of intestinal mitochondria. The mitochondria of intestinal epithelial cells are of great significance for promoting intestinal motility and maintaining intestinal metabolism. It is necessary for the prophylaxis and therapy of intestinal metabolism-related diseases to improve mitochondrial function. We investigated the effect of 4,6-diamino-2-pyrimidinethiol-modified gold nanoparticles (D-Au NPs) on intestinal mitochondria and studied the regulatory role of D-Au NPs on mitochondria metabolism-related disease. D-Au NPs improved the antioxidation capability of mitochondria, regulated the mitochondrial metabolism, and maintained intestinal cellular homeostasis via the activation of AMPK and regulation of PGC-1α with its downstream signaling (UCP2 and DRP1), enhancing the intestinal mechanical barrier. D-Au NPs improved the intestinal mitochondrial function to intervene in the emergence of constipation, which could help develop drugs to treat and prevent mitochondrial metabolism-related diseases. Our findings provided an in-depth understanding of the mitochondrial effects of Au NPs for improving human intestinal barriers.


Fast pulse shaping for a novel gated electron mirror.
We present the design and prototype of a switchable electron mirror, along with a technique for driving it with an arbitrary pulse shape. We employ a general technique for electronic pulse-shaping, where high fidelity of the pulse shape is required, but the characteristics of the system, which are possibly nonlinear, are not known. This driving technique uses an arbitrary waveform generator to pre-compensate the pulse, with a simple iterative algorithm used to generate the input waveform. This is a broadly applicable, general method for arbitrary pulse shaping. Driving our switchable electron mirror with a flat-top pulse, we demonstrate an improvement in rms error of roughly two orders of magnitude compared to an uncompensated waveform. Our results demonstrate the feasibility of high fidelity waveform reproduction in the presence of nonidealities, with immediate applications in the realization of novel electron optical components.


Conformational Nonequilibrium Enzyme Kinetics: Generalized Michaelis-Menten Equation.
In a conformational nonequilibrium steady state (cNESS), enzyme turnover is modulated by the underlying conformational dynamics. On the basis of a discrete kinetic network model, we use an integrated probability flux balance method to derive the cNESS turnover rate for a conformation-modulated enzymatic reaction. The traditional Michaelis-Menten (MM) rate equation is extended to a generalized form, which includes non-MM corrections induced by conformational population currents within combined cyclic kinetic loops. When conformational detailed balance is satisfied, the turnover rate reduces to the MM functional form, explaining its general validity. For the first time, a one-to-one correspondence is established between non-MM terms and combined cyclic loops with unbalanced conformational currents. Cooperativity resulting from nonequilibrium conformational dynamics can be achieved in enzymatic reactions, and we provide a novel, rigorous means of predicting and characterizing such behavior. Our generalized MM equation affords a systematic approach for exploring cNESS enzyme kinetics.


Revision surgery for lumbar pseudarthrosis.
Revision surgery for pseudarthrosis after a lumbar spinal fusion has unpredictable functional results. The aim of this study was to determine the clinical outcomes of revision surgery to fuse the pseudarthrosis site based on the two most common diagnoses (degenerative disc disease [DDD] vs. spondylolisthesis). Patients who had a revision surgery between 1995 and 2004 for lumbar pseudarthrosis after short segment lumbar spinal fusion were identified through the institution's Spine Center surgery database. A retrospective chart review of clinical, hospital, and anesthesia records was then performed. Sixty-six patients were included in the study (28 patients with DDD and 38 patients with spondylolisthesis). Inclusion criteria were a surgical diagnosis of pseudarthrosis with a prior fusion of one or two motion segments, minimum 24 months of follow-up, and a diagnosis of either symptomatic DDD or spondylolisthesis as the primary indication for the index fusion surgery. The Oswestry disability index (ODI) and a self-assessment questionnaire were used to evaluate clinical outcomes. A retrospective chart and radiographic review was performed. Statistical analysis was done using Student t test for ODI scores and chi-square test for discrete variables from the outcome questionnaires. Follow-up radiographs were available for 64 patients (97%), and a fusion rate of 100% was found in both groups for the radiographs examined. The mean postoperative ODI score was 53.3 (30-84.4) for DDD patients and 37.2 (2.5-76) for the spondylolisthesis group (p<.01). Only 50% of the patients in the DDD group felt that their overall well-being had improved since the surgery. In the spondylolisthesis group, 64% of patients stated that their overall well-being had improved since their revision surgery. The clinical outcomes after revision surgery for pseudarthrosis are worse in patients with DDD compared with spondylolisthesis despite successful repair of nonunion. Risks and benefits should be well discussed with the patients before deciding on surgical treatment for the management of pseudarthrosis, especially in patients with previous short-segment fusions done for DDD.


Novel DNA methylation profiles associated with key gene regulation and transcription pathways in blood and placenta of growth-restricted neonates.
Fetal growth is determined by the feto-placental genome interacting with the maternal in utero environment. Failure of this interplay leads to poor placental development and fetal growth restriction (FGR), which is associated with future metabolic disease. We investigated whether whole genome methylation differences existed in umbilical cord blood and placenta, between gestational-matched, FGR, and appropriately grown (AGA) neonates. Using the Infinium HumanMethylation450 BeadChip®, we found that DNA from umbilical cord blood of FGR born at term (n = 19) had 839 differentially methylated positions (DMPs) that reached genome-wide significance compared with AGA (n = 18). Using gestational age as a continuous variable, we identified 76,249 DMPs in cord blood (adj. P < 0.05) of which 121 DMPs were common to the 839 DMPs and were still evident when comparing 12 FGR with 12 AGA [39.9 ± 1.2 vs. 40.0 ± 1.0 weeks (mean ± SD), respectively]. A total of 53 DMPs had a β methylation difference >10% and 25 genes were co-methylated more than twice within 1000 base pairs. Gene Ontology (GO) analysis of DMPs supported their involvement in gene regulation and transcription pathways related to organ development and metabolic function. A similar profile of DMPs was found across different cell types in the cord blood. At term, no DMPs between FGR and AGA placentae reached genome-wide significance, validated with an external dataset. GO analysis of 284 pre-term, placental DMPs associated with autophagy, oxidative stress and hormonal responses. Growth restricted neonates have distinct DNA methylation profiles in pre-term placenta and in cord blood at birth, which may predispose to future adult disease.


Risk Factors for Permanent Pacemaker after Implantation of Surgical or Percutaneous Self-Expanding Aortic Prostheses.
The use of transcatheter aortic valve implantation (TAVI) following the introduction of Nitinol autoexpandable devices has spread rapidly during recent years. In addition, cardiac surgery has been revolutionized due to the use of Nitinol-based sutureless prostheses for aortic valve replacement (AVR). During the same period, however, permanent pacemaker (PPM) implantation has emerged as a frequent complication. The study aim was to identify the risk factors of PPM following the implantation of a Nitinol self-expanding prosthesis (for AVR or TAVI). A study group was created between two institutions experienced in the use of nitinol devices, and a pool of 336 patients (56.6% CoreValve - Medtronic; 43.4% Perceval - Sorin) was available for a retrospective analysis. Pre-procedural clinical and electrocardiography (ECG) variables and postprocedural ECG variables were compared between the PPM group and control patients who had not received a PPM during their index hospitalization. A PPM was required in 12.8% of patients (TAVI 17.5% versus AVR 6.8%, p = 0.007). PPM patients had a higher logistical EuroSCORE (median 20.77% versus 15.59%, p = 0.015), a lower use of statins (18.6% versus 34.2%, p = 0.04), a pre-procedural longer QRS interval (median 117 ms versus 98 ms, p = 0.002), and a higher incidence of conduction disturbances (29.3% versus 16.8%, p = 0.034), with a prevalence of right bundle branch block. At the first postprocedural ECG, non-stimulated PPM patients had a longer QRS interval (median 150 ms versus 113 ms, p<0.001) and a longer QTc interval (487.3 ± 46 ms versus 510.8 ± 53.8 ms, p = 0.005). Prevalent intra-ventricular conduction disorders in both groups included left bundle branch block. AVR patients received a PPM later than the TAVI group (median 6 days versus 3 days, p = 0.01). TAVI was an independent predictor of PPM at logistic regression analysis (OR 3.18; 95% CI 1.19-8.48, p = 0.021), but the significance disappeared after incorporating post-procedural ECG variables. Nitinol technology is a ground-breaking option for aortic valve procedures. However, the radial forces of the self-expandable mechanism may be implicated in the increased need for PPM, mostly in cases of TAVI compared to AVR, that most likely are due to displacement of the stent provoked by in situ calcium clusters. Given the clinical and economic impact of PPM, new parameters are required to understand the stent/tissue interaction and to help with device selection.


A mutation in a novel ATP-dependent Lon protease gene in a kindred with mild mental retardation.
Identifying the genetic factors that contribute to memory and learning is limited by the complexity of brain development and the lack of suitable human models for mild disorders of cognition. Previously, a disease locus was mapped for a mild type of nonsyndromic mental retardation (IQ between 50 and 70) to a 4.2-MB interval on chromosome 3p25-pter in a large kindred. The genes and transcripts within the candidate region were systematically analyzed for mutations by single-strand polymorphism analysis and DNA sequencing. A nonsense mutation causing a premature stop codon in a novel gene (cereblon; CRBN) was identified that encodes for an ATP-dependent Lon protease. The predicted protein sequence is highly conserved across species, and it belongs to a family of proteins that selectively degrade short-lived polypeptides and regulate mitochondrial replication and transcription. One member of the Lon-containing protein family is regionally expressed in the human hippocampus, an important neuroanatomic region that is involved in long-term potentiation and learning. The mutation in the CRBN gene described interrupts an N-myristoylation site and eliminates a casein kinase II phosphorylation site at the C terminus. A gene on chromosome 3p that is associated with mild mental retardation in a large kindred is reported. This finding implicates a role for the ATP-dependent degradation of proteins in memory and learning.


Adenocarcinoma of the small bowel in association with regional enteritis. Four new cases.
Four cases of carcinoma of the small bowel following chronic regional enteritis are presented. Search of the medical literature revealed 31 other cases reported up to the present. We must entertain the possibility that chronic regional enteritis may predispose to the development of cancer of the small bowel.


Blood conservation in cardiac operations. Cell separation versus hemofiltration.
The effects of hemoconcentration performed during and after extracorporeal circulation by either centrifugation (cell separation group, n = 20) or hemofiltration (n = 20) were investigated in 40 patients undergoing elective aorta-coronary bypass grafting. Interest was focused on the quality of the blood concentrated from the blood remaining in the extracorporeal circuit and on the reaction of the patients after retransfusion of the concentrated products. Hemofiltration was easy to perform and produced whole blood quicker than the cell separation technique. Coagulation studies revealed no significant differences in heparin concentration, levels of fibrinogen and antithrombin III, or platelet counts. Various coagulation parameters tended to normalize completely and more quickly after hemofiltration than after centrifugation. None of the patients had severe bleeding postoperatively. Free hemoglobin levels were not affected by hemofiltration; elastase concentration was higher only immediately after retransfusion of the concentrated blood, with no effect on organ function. We conclude that both methods were effective means of hemoconcentration during extracorporeal circulation and in salvaging the diluted pump blood after extracorporeal circulation. Loss of plasma fraction is an important disadvantage in the centrifugation technique, which can be avoided by hemofiltration; derangement in colloid osmotic pressure and coagulation parameters was less pronounced after hemofiltration. Costs were lower, as well. Therefore, when a high volume of cardioplegic solution and two-stage cannulation are used, hemofiltration seems to be the method of choice for blood conservation during cardiac operations.


Mixed Metal-Organic Framework Stationary Phases for Liquid Chromatography.
Strategic design of the stationary phase in liquid chromatography (LC) is crucial for modern separation science. Herein, a design approach using mixed metal-organic frameworks (MOFs) as tunable LC stationary phases is proposed. Three MOFs with an isostructural pillared-layer structure are employed, with pore sizes tuned by the systematic design of the constituent ligands, using 1,4-benzenedicarboxylate (bdc), 1,4-naphthalenedicarboxylate (ndc), and 9,10-anthracenedicarboxylate (adc). Packed columns filled with the MOFs and their mixed-particle/solid-solution stationary phases are prepared and examined for the retention capability of polyethylene glycol (PEG) in LC. While the MOF-packed columns filled with binary mixtures of different MOF particles provide good control of the retention with respect to the particle mixing ratio, the columns filled with mixed-linker solid-solution MOFs show a significant multicomponent effect on the retention behavior. Specifically, mixed-linker solid-solution MOFs consisting of bdc/ndc binary ligands are found to show a strong retention that surpasses even their parent MOFs, namely, pure bdc- and ndc-MOF stationary phases. The retention behavior on the MOF-packed columns is explained by the specific nanostructures of the solid-solution MOFs, which affects the balance between substrate affinity and adsorption kinetics into the MOF pores, dictating the total retention capability. The results provide an extra dimension for stationary phase design using MOFs as a promising recognition medium for LC.


STEM electron beam-induced current measurements of organic-inorganic perovskite solar cells.
We describe a new approach for preparing organic-inorganic perovskite solar cells for electron beam-induced current (EBIC) measurements in plan-view geometry. This method substantially reduces sample preparation artefacts, provides good electrical contact and keeps the preparation steps as close as possible to those for real devices. Our EBIC images were acquired simultaneously with annular dark-field scanning transmission electron microscopy images using a home-made highly sensitive EBIC amplifier. High-angle annular dark-field images and energy dispersive X-ray maps were recorded from the same area immediately afterwards. This allowed the EBIC contrast to be correlated with regions containing N and a deficiency of O. The EBIC contrast was also found to be similar to secondary electron contrast recorded with a scanning electron microscope. By identifying the generation and absorption electron processes, we determine that EBIC cannot be separated from the secondary electron and absorbed currents. This means that careful analysis needs to be performed before conclusions can be made on the origin of the current measured across p-n or p-i-n junctions.


Transient lingual papillitis associated with confirmed herpes simplex virus 1 in a patient with kawasaki disease.
We present a case of transient lingual papillitis associated with confirmed herpes simplex virus 1 that developed after a child received intravenous immunoglobulin and infliximab for acute Kawasaki disease.


Initial clinical experience with ICI 141,292 (Visacor), a new selective beta 1-adrenoceptor blocker with ISA--a multicentre trial in 59 patients.
The objective of this placebo controlled double-blind multicentre (six centres) trial was to investigate the safety and efficacy of ICI 141,292 (Visacor), a new selective beta 1-adrenoceptor antagonist with modest intrinsic sympathomimetic activity (ISA), in hypertensive patients. Fifty-nine patients with mild essential hypertension were randomized to two of five treatment alternatives (placebo, 50 mg, 100 mg 200 mg or 300 mg of ICI 141,292) each given once daily for 2 weeks with a 4 week placebo period before (run in) and in between (wash out) active periods. Thus, each of the five treatments was evaluated in 20-24 patients. After 2 weeks (24 h after last dose) the reduction in recumbent blood pressure for all doses except 50 mg of ICI 141,292 was statistically significant and in the order of 6/4 mm Hg. Standing systolic blood pressure was reduced in a dose-dependent way but only significant for 200 mg of ICI 141,292 (8 mm Hg). Heart rate changes (delta) less than 4 beats/min) were not statistically significant for any dose. It is concluded that ICI 141,292 was well tolerated and had a significant but weak antihypertensive effect which might be explained by too much beta 1-adrenoceptor ISA.


Hormonal control of the floral transition: Can one catch them all?
The transition to flowering marks a key adaptive developmental switch in plants which impacts on their survival and fitness. Different signaling pathways control the floral transition, conveying both endogenous and environmental cues. These cues are often relayed and/or modulated by different hormones, which might confer additional developmental flexibility to the floral process in the face of varying conditions. Among the different hormonal pathways, the phytohormone gibberellic acid (GA) plays a dominant role. GA is connected with the other floral pathways through the GA-regulated DELLA proteins, acting as versatile interacting modules for different signaling proteins. In this review, I will highlight the role of DELLAs as spatial and temporal modulators of different consolidated floral pathways. Next, building on recent data, I will provide an update on some emerging themes connecting other hormone signaling cascades to flowering time control. I will finally provide examples for some established as well as potential cross-regulatory mechanisms between hormonal pathways mediated by the DELLA proteins.


Enhancing effect of chitosan on methylene blue-mediated photodynamic therapy against C. albicans: A study in planktonic growth, biofilms, and persister cells.
Chitosan (CS) is a natural polymer extracted from the exoskeleton of crustaceans. Due to its cationic structure, CS has been studied as a possible enhancer of antimicrobial photodynamic therapy (aPDT). The objective was to evaluate the association of CS with methylene blue (MB)-mediated aPDT on Candida albicans, investigating its effects on planktonic growth, biofilms, and cells persistent to fluconazole. The ability of CS to interfere with MB absorption by Candida cells was also evaluated. For the assays, planktonic cells of C. albicans were cultivated for 24 h, and the biofilms were formed for 48 h. For the induction of persister cells, C. albicans was cultivated with high concentration of fluconazole for 48 h. Treatments were performed with MB, CS or MB+CS, followed by irradiation with LED (660 nm ). As results, aPDT with MB (300 µm) reduced the planktonic cells by 1.6 log10 CFU, while the MB+CS association led to a reduction of 4.8 log10 CFU. For aPDT in biofilms, there was a microbial reduction of 2.9 log10 CFU for the treatment with MB (600 µm) and 5.3 log10 CFU for MB+CS. In relation to persister cells, the fungal reductions were 0.4 log10 CFU for MB and 1.5 log10 CFU for MB+CS. In the absorption assays, the penetration of MB into Candida cells was increased in the presence of CS. It was concluded that CS enhanced the antimicrobial activity of aPDT in planktonic growth, biofilms, and persister cells of C. albicans, probably by facilitating the penetration of MB into fungal cells.


What is the real cardiac anatomy?
The heart is a remarkably complex organ. Teaching its details to medical students and clinical trainees can be very difficult. Despite the complexity, accurate recognition of these details is a pre-requisite for the subsequent understanding of clinical cardiologists and cardiac surgeons. A recent publication promoted the benefits of virtual reconstructions in facilitating the initial understanding achieved by medical students. If such teaching is to achieve its greatest value, the datasets used to provide the virtual images should themselves be anatomically accurate. They should also take note of a basic rule of human anatomy, namely that components of all organs should be described as they are normally situated within the body. It is almost universal at present for textbooks of anatomy to illustrate the heart as if removed from the body and positioned on its apex, the so-called Valentine situation. In the years prior to the emergence of interventional techniques to treat cardiac diseases, this approach was of limited significance. Nowadays, therapeutic interventions are commonplace worldwide. Advances in three-dimensional imaging technology, furthermore, now mean that the separate components of the heart can readily be segmented, and then shown in attitudinally appropriate fashion. In this review, we demonstrate how such virtual dissection of computed tomographic datasets in attitudinally appropriate fashion reveals the true details of cardiac anatomy. The virtual approach to teaching the arrangement of the cardiac components has much to commend it. If it is to be used, nonetheless, the anatomical details on which the reconstructions are based must be accurate. Clin. Anat. 32:288-309, 2019. © 2019 The Authors. Clinical Anatomy published by Wiley Periodicals, Inc. on behalf of American Association of Clinical Anatomists.


Curcumin Inhibits Replication of Human Parainfluenza Virus Type 3 by Affecting Viral Inclusion Body Formation.
Human Parainfluenza Virus Type 3 (HPIV3) is one of the main pathogens that cause acute lower respiratory tract infections in infants and young children. However, there are currently no effective antiviral drugs and vaccines. Herein, we found that a natural compound, curcumin, inhibits HPIV3 infection and has antiviral effects on entry and replication of the virus life cycle. Immunofluorescence and western blotting experiments revealed that curcumin disrupts F-actin and inhibits viral inclusion body (IB) formation, thus inhibiting virus replication. Curcumin can also downregulate cellular PI4KB and interrupt its colocalization in viral IBs. This study verified the antiviral ability of curcumin on HPIV3 infection and preliminarily elucidated its influence on viral replication, providing a theoretical basis for antiviral drug development of HPIV3 and other parainfluenza viruses.


PD-L1, Galectin-9 and CD8+ tumor-infiltrating lymphocytes are associated with survival in hepatocellular carcinoma.
Novel systemic treatments for hepatocellular carcinoma (HCC) are strongly needed. Immunotherapy is a promising strategy that can induce specific antitumor immune responses. Understanding the mechanisms of immune resistance by HCC is crucial for development of suitable immunotherapeutics. We used immunohistochemistry on tissue-microarrays to examine the co-expression of the immune inhibiting molecules PD-L1, Galectin-9, HVEM and IDO, as well as tumor CD8+ lymphocyte infiltration in HCC, in two independent cohorts of patients. We found that at least some expression in tumor cells was seen in 97% of cases for HVEM, 83% for PD-L1, 79% for Gal-9 and 66% for IDO. In the discovery cohort (n = 94), we found that lack of, or low, tumor expression of PD-L1 (p < 0.001), Galectin-9 (p < 0.001) and HVEM (p < 0.001), and low CD8+TIL count (p = 0.016), were associated with poor HCC-specific survival. PD-L1, Galectin-9 and CD8+TIL count were predictive of HCC-specific survival independent of baseline clinicopathologic characteristics and the combination of these markers was a powerful predictor of HCC-specific survival (HR 0.29; p <0.001). These results were confirmed in the validation cohort (n = 60). We show that low expression levels of PD-L1 and Gal-9 in combination with low CD8+TIL count predict extremely poor HCC-specific survival and it requires a change in two of these parameters to significantly improve prognosis. In conclusion, intra-tumoral expression of these immune inhibiting molecules was observed in the majority of HCC patients. Low expression of PD-L1 and Galectin-9 and low CD8+TIL count are associated with poor HCC-specific survival. Combining immune biomarkers leads to superior predictors of HCC mortality.


A new paramutation-like example at the Delta gene of Drosophila.
The hereditary transmission of a phenotype independent from DNA sequence implies epigenetic effects. Paramutation is a heritable epigenetic phenomenon observed in plants and animals. To investigate paramutation in Drosophila, we used the P{ry+t7.2 = PZ}Dl05151 P-element insertion in the Drosophila melanogaster genome that causes a dominant visible phenotype: the presence of characteristic extra-veins in the fly wings. This extra-vein phenotype presents variable expressivity and incomplete penetrance. The insert is a PZ element located 680 bp upstream from the ATG of the Delta (Dl) gene, encoding the Notch ligand involved in wing vein development, and acts as a null allele. In the G2 offspring from a cross between the heterozygous transgenic stock and wild-type flies, we observed the transmission of the extra-vein phenotype to wild-type flies without the transgene, independently of gender and across many generations. This is a "paramutation-like" example in the fly: the heritable transmission of a phenotypic change not linked to a classical genetic mutation. A "paramutagenic" allele in heterozygotes transmits the phenotype of the heterozygotes to the wild-type allele ("paramutant") in a stable manner through generations. Distinct from paramutation events so far described in Drosophila, here we deal with a dominant effect on a single gene involving variable hereditary signals.


Top-of-Climb Matching Method for Reducing Aircraft Trajectory Prediction Errors.
The inaccuracies of the aircraft performance models utilized by trajectory predictors with regard to takeoff weight, thrust, climb profile, and other parameters result in altitude errors during the climb phase that often exceed the vertical separation standard of 1000 feet. This study investigates the potential reduction in altitude trajectory prediction errors that could be achieved for climbing flights if just one additional parameter is made available: top-of-climb (TOC) time. The TOC-matching method developed and evaluated in this paper is straightforward: a set of candidate trajectory predictions is generated using different aircraft weight parameters, and the one that most closely matches TOC in terms of time is selected. This algorithm was tested using more than 1000 climbing flights in Fort Worth Center. Compared to the baseline trajectory predictions of a real-time research prototype (Center/TRACON Automation System), the TOC-matching method reduced the altitude root mean square error (RMSE) for a 5-minute prediction time by 38%. It also decreased the percentage of flights with absolute altitude error greater than the vertical separation standard of 1000 ft for the same look-ahead time from 55% to 30%.


Carbapenem-Resistant Klebsiella pneumoniae Osteomyelitis Treated with Ceftazidime-Avibactam in an Infant: A Case Report.
Increasing cases of carbapenem-resistant Klebsiella pneumoniae (CR-KP) infections have been observed globally where multi-drug resistance to CR-KP can make the infection difficult to treat. In recent years, the β-lactam/β-lactamase inhibitor, ceftazidime-avibactam (CAZ-AVI), has been developed to treat complicated urinary tract infections and complicated intra-abdominal infections. CAZ-AVI is approved for children over 3-month old but has yet to be investigated for cases of osteomyelitis. Only three case reports exist in literature on the use of CAZ-AVI for CR-KP osteomyelitis in adults. In this report, we present an infant with primary hematogenous osteomyelitis and septic arthritis in the right shoulder following surgical treatment for a heart murmur. Bacterial isolation revealed a strain of CR-KP, which was successfully treated with CAZ-AVI after initial administration of imipenem-based treatments.


Nitric Oxide and its Derivatives Containing Nasal Spray and Inhalation Therapy for the Treatment of COVID-19.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a major health concern worldwide and has evolved into different variants. SARS-CoV-2 possesses a spike glycoprotein on its envelope that binds to the angiotensin-converting enzyme 2 (ACE-2) receptor of the host cell via the receptor-binding domain (RBD) in the upper respiratory tract. Since the SARS-CoV-2 virus variants change the severity of the diesease and treatment scenarios, repurposing current medicines may provide a quick and appealing method with established safety features. The efficacy and safety of antiviral medicines against the coronavirus disease 2019 (COVID-19) have been investigated, and several of them are now undergoing clinical studies. Recently, it has been found that nitric oxide (NO) shows antiviral properties against SARS-CoV-2 and prevents the virus from binding to a host cell. In addition, NO is a well-known vasodilator and acts as an important coagulation mediator. With the fast-track development of COVID-19 treatments and vaccines, one avenue of research aimed at improving therapeutics is exploring different forms of drug delivery, including intranasal sprays and inhalation therapy. The nasal mucosa is more prone to be the site of infection as it is in more direct contact with the physical environment via air during inhalation and exhalation. Thus, the use of exogenous nasal NO therapy via the intranasal route displays a distinct advantage. Therefore, the objective of this review is to summarize the relevant actions of NO via the intranasal spray and inhalation delivery, its mechanism of action, and its use in the treatment of COVID-19.


Contrast Sensitivity in Early to Intermediate Age-Related Macular Degeneration (AMD).
Previous studies indicated that advanced age-related macular degeneration (AMD) affects contrast sensitivity (CS) in humans. The CS results for early/intermediate AMD patients are contradictory. The purpose of this study was to determine if CS testing discriminates early/intermediate AMD patients with normal acuity from normal patients. Forty-nine subjects (25 control and 24 early/intermediate AMD patients) were chosen for this project. The age (p = .16) and acuity (p = .34) was not significantly different between the groups. The average simplified AREDS AMD grade for the AMD patients was 2.75 ± 1.03. Three CS functions employing a descending method of limits were measured at the fovea (1. stationary stimulus and, 2. 16 Hz counter-phase stimulus under photopic conditions and 3. the stationary stimulus viewed through a 2 log unit neutral density filter (mesopic condition, background luminance of 1 cd/m2)) and at 4 deg right or left of the fovea with a horizontally oriented sine wave grating (5 deg diameter) viewed on a VPixx monitor (luminance of 100 cd/m2). The early AMD patients were no different from the control patients for any test condition. The intermediate AMD patients were significantly different from the control patients for the mesopic CS function (p = .05). Post-hoc 2-sample t-tests for the intermediate AMD patients were significantly different from the control patients under the stationary photopic and mesopic conditions for the 1.5 cycle per degree stimulus. Group differences in CS were only found in intermediate AMD patients. The loss in CS increased for the intermediate AMD patients under low light levels. Thus, CS may not be the optimal test to discriminate early AMD from control patients so other tests measured under dark adapted conditions should be investigated.


Behavioural alterations induced by intermittent ethanol intake and noise exposure in adolescent rats.
Alcohol intake and exposure to noise are common activities of human adolescents performed in entertainment contexts worldwide that can induce behavioural disturbances. Therefore, the aim of the present work was to investigate in an experimental model of adolescent animals whether noise exposure and intermittent ethanol intake, when present individually or sequentially, might be able to modify different behaviours. Adolescent Wistar rats of both sexes were subjected to voluntary intermittent ethanol intake for 1 week followed by exposure to noise for 2 h and tested in a battery of behavioural tasks. Data show that males exposed to noise experienced a deficit in associative memory (AM), increase in anxiety-like behaviours (ALB) and altered reaction to novelty (RN) when compared with sham animals, whereas females also showed an increase in risk assessment behaviours (RABs) and a decrease in exploratory activity (EA). In contrast, ethanol intake induced an increase in RAB and RN in males and females, whereas females also showed a deficit in AM and EA as well as an increase in ALB. When ethanol was ingested before noise exposure, most parameters were counteracted both in male and females, but differed among sexes. In consequence, it could be hypothesized that an environmental acute stressor like noise might trigger a behavioural counteracting induced by a previous repeated exposure to a chemical agent such as ethanol, leading to a compensation of a non-adaptive behaviour and reaching a better adjustment to the environment.


Detection of blood volumes and haemoglobin mass by means of CO re-breathing and indocyanine green and sodium fluorescein injections.
The main aim of the present study was to quantify the magnitude of differences introduced when estimating a given blood volume compartment (e.g. plasma volume) through the direct determination of another compartment (e.g. red cell volume) by multiplication of venous haematocrit and/or haemoglobin concentration. However, since whole body haematocrit is higher than venous haematocrit such an approach might comprise certain errors. To test this experimentally, four different methods for detecting blood volumes and haemoglobin mass (Hbmass) were compared, namely the carbon monoxide (CO) re-breathing (for Hbmass), the indocyanine green (ICG; for plasma volume [PV]) and the sodium fluorescein (SoF; for red blood cell volume [RBCV]) methods. No difference between ICG and CO re-breathing derived PV could be established when a whole body/venous haematocrit correction factor of 0.91 was applied (p = 0.11, r = 0.43, mean difference -340 ± 612 mL). In contrast, when comparing RBCV derived by the CO re-breathing and the SoF method, the SoF method revealed lower RBCV values as compared to the CO re-breathing method (p < 0.05, r = 0.95, mean difference -728 ± 184 mL). However, compared to the ICG and the SoF methods, the typical error (%TE) and hence reliability of the CO re-breathing method was lower for all measured parameters. Therefore, estimating blood volume compartments by the direct assessment of another compartment can be considered a suitable approach. The CO re-breathing method proved accurate in determining the induced phlebotomy and is at the same time judged easier to perform than any of the other methods.


Supramolecular Photochemistry in Solution and on Surfaces: Encapsulation and Dynamics of Guest Molecules and Communication between Encapsulated and Free Molecules.
Supramolecular assemblies that help to preorganize reactant molecules have played an important role in the development of concepts related to the control of excited-state processes. This has led to a persistent search for newer supramolecular systems (hosts), and this review briefly presents our work with octa acid (OA) to a host to control excited-state processes of organic molecules. Octa acid, a water-soluble host, forms 1:1, 2:1, and 2:2 (host-guest) complexes with various organic molecules. A majority of the guest molecules are enclosed within a capsule made up of two molecules of OA whereas OA by itself remains as a monomer or aggregates. Luminescence and (1)H NMR spectroscopy help to characterize the structure and dynamics of these host-guest complexes. The guest molecule as well as the host-guest complex as a whole undergoes various types of motion, suggesting that the guests possess freedom inside the confined space of the octa acid capsule. In addition, the confined guests are not isolated but are able to communicate (energy, electron, and spin) with molecules present closer to the capsule. The host-guest complexes are stable even on solid surfaces such as silica, clay, α-Zr phosphate, TiO2, and gold nanoparticles. This opens up new opportunities to explore the interaction between confined guests and active surfaces of TiO2 and gold nanoparticles. In addition, this allows the possibility of performing energy and electron transfer between organic molecules that do not adsorb on inert surfaces of silica, clay, or α-Zr phosphate. The results summarized here, in addition to providing a fundamental understanding of the behavior of molecules in a confined space provided by the host OA, are likely to have a long-range effect on the capture and release of solar energy.


Highly Efficient Vacancy-Driven Photothermal Therapy Mediated by Ultrathin MnO2 Nanosheets.
In medical applications, two-dimensional nanomaterials have been widely studied on account of their intriguing properties such as good biocompatibility, stability, and multifunctionality. Herein, an ultrathin MnO2 nanosheet has been fabricated by a simplistic hydrothermal process. The high photothermal conversion performance (62.4%) can be attributed to the vacancy in the ultrathin MnO2 nanosheet, as confirmed by the extended X-ray absorption fine structure results and the density functional theory calculation, benefiting photoacoustic imaging-guided cancer therapy. This highly efficient vacancy-induced photothermal therapy has been reported for the first time. As a result, this work demonstrates that this ultrathin MnO2 nanosheet has a potential to construct a nanosystem for imaging-guided cancer therapy.


Stability of three cephalosporin antibiotics in AutoDose Infusion System bags.
To evaluate the physical and chemical stability of three commonly used cephalosporin antibiotic solutions packaged in AutoDose Infusion System bags stored and evaluated at appropriate intervals for up to 7 days at 23 degrees C and up to 30 days at 4 degrees C. Laboratory. The test samples were prepared by adding the required amount of the cephalosporin antibiotic to the AutoDose Infusion System bags and diluting to the target concentration with 0.9% sodium chloride injection. Physical stability and chemical stability based on drug concentrations initially and at appropriate intervals over periods of up to 7 days at 23 degrees C and up to 30 days at 4 degrees C. All of the cephalosporin admixtures were clear when viewed in normal fluorescent room light and with a Tyndall beam. Measured turbidity and particulate content were low and exhibited little change. The cefazolin sodium-containing samples were colorless throughout the study. The admixtures with ceftazidime and ceftriaxone sodium had a slight yellow tinge initially, and the room temperature samples turned a frank yellow color after 5 days. The refrigerated samples did not change color. High-performance liquid chromatography analysis showed that cefazolin sodium and ceftriaxone sodium remained stable for 30 days and ceftazidime remained stable for 7 days at 4 degrees C. At room temperature, losses were much more rapid. Cefazolin sodium and ceftriaxone sodium retained at least 90% of their initial concentrations through 7 days and 5 days, respectively, when stored at 23 degrees C. Ceftazidime remained stable for only 1 day at 23 degrees C. Cefazolin sodium, ceftazidime, and ceftriaxone sodium exhibited physical and chemical stabilities consistent with those found in previous studies of these drugs. The AutoDose Infusion System bags did not adversely affect the physical and chemical stabilities of these three cephalosporin antibiotics.


MiR-32 promotes gastric carcinoma tumorigenesis by targeting Kruppel-like factor 4.
Gastric cancer (GC) is a prevalent malignant cancer worldwide and is highly lethal because of its fast growth. Currently, the clinical therapy options for GC remain limited. MiR-32 has been reported as an oncogenic microRNA in many cancers, but its role in GC is unclear. Here, we found that miR-32 was overexpressed in GC tissues compared with adjacent normal tissue, and miR-32 was higher in GC patients' plasma compared with healthy individuals. Furthermore, we have identified miR-32 to be oncogenic, by promoting gastric cell proliferation, migration and invasion. We also identified Kruppel-like factor 4 (KLF4) as a direct target of miR-32. Knockdown of KLF4 promoted proliferation, migration and invasion of GC cells. We conclude that miR-32 promotes GC cell proliferation, migration and invasion by targeting KLF4, suggesting that the miR-32-KLF4 pathway may be useful in clinical diagnosis and therapeutics.


Unique example of flexible phenol coordination in mononuclear manganese compounds.
The synthesis and characterization of six novel mononuclear Mn(II) and Mn(III) complexes are presented. The tripodal ligands 2-((bis(pyridin-2-ylmethyl)amino)methyl)-4-nitrophenol (HL1), 2-[[((6-methylpyridin-2-yl)methyl)(pyridin-2-ylmethyl)amino]methyl]-4-nitrophenol (HL2), (2-pyridylmethyl)(6-methyl-2-pyridylmethyl)(2-hydroxybenzyl)amine (HL3) and 2-((bis(pyridin-2-ylmethyl)amino)methyl)-4-bromophenol were used. All ligands provide an N3O donor set. The compounds [Mn(II)(HL1)Cl2].CH3OH (1), [Mn(III)(L1)Cl2] (2), [Mn(II)(HL2)(EtOH)Cl2] (3), [Mn(II)(HL3)Cl2].CH3OH (4), [Mn(III)(HL4)Br2] (5) and [Mn(III)(L1)(tcc)] (6), with tcc = tetrachlorocatecholate dianion, were synthesized and characterized by various techniques such as X-ray crystallography, mass spectrometry, IR and UV-vis spectroscopy, cyclic voltammetry, and elemental analysis. Compound 1 crystallizes in the triclinic space group P1, compounds 2, 3 and 4 were solved in the monoclinic space group P2(1)/c, whereas the structure determination of and succeeded in the orthorhombic space groups Pbca and P2(1)2(1)2(1), respectively. Notably, the crystal structures of 1 and 3 are the first Mn(II) complexes featuring a non-coordinating phenol moiety. Compound 2 oxidizes 3,5-di-tert-butylcatechol to 3,5-di-tert-butylquinone exhibiting saturation kinetics at high substrate concentrations with a turnover number of kcat = 173 h(-1). The electronic influence of different substituents in para position of the phenol group is lined out.


A comparison of self-reported dental health attitudes and behavior between selected Japanese and Australian students.
To compare cross-cultural differences of dental health behavior, 376 dental students in Japan and 213 in Australia were surveyed using a twenty-item Hiroshima University-Dental Behavior Inventory (HU-DBI) questionnaire (in Japanese and English versions respectively). The mean DBI score of Year 1 Australian students was significantly greater than that of their Japanese peers (Australian 6.56, Japanese 5.57; P < 0.001), which suggested a higher level of dental health awareness in Australian students on entry. Only 7 percent of the Japanese students had been told by their dentist that they were performing a high level of plaque control, as contrasted with 50 percent of the Australian students. Furthermore, while only a small proportion of the Australian students (8 percent) reported a belief that they may eventually require dentures, 37 percent of the Japanese students held this belief (P < 0.001). The mean HU-DBI score of the Japanese students was lower than that of the Australian students until Year 4. Differences between the genders were not a major feature.


Differential effects of structurally unrelated chemical irritants on the density and morphology of epidermal CD1+ cells.
In order to gain a greater insight into the complex mechanisms of action of different irritant chemicals on the skin, we have studied the behavior of epidermal CD1+ cells in experimentally induced irritant contact dermatitis. Healthy, human volunteers were patch tested for 48 h with the following six chemically unrelated irritants and their appropriate vehicle controls; benzalkonium chloride, sodium lauryl sulphate, dithranol, nonanoic acid, croton oil, and propylene glycol. After visually assessing and grading the resulting inflammatory reactions, punch biopsies were taken and the morphology and density of CD1+ cells in the epidermis studied using immunocytochemical techniques in combination with image analysis and electron microscopy. Statistically significant decreases in the epidermal density of CD1+ cells occurred in the responses to dithranol (p less than 0.05) and nonanoic acid (p less than 0.01). Importantly, these changes in density were not simply due to variations in the intensity of inflammatory response (r = 0.1157). Alterations in the length of the dendritic processes of CD1+ cells were also induced, and semi-quantitative analysis revealed significant decreases in dendrite length in the reactions to sodium lauryl sulphate (p less than 0.05), nonanoic acid (p less than 0.001), croton oil (p less than 0.05), and dithranol (p less than 0.005). Unlike epidermal density, however, this effect on cell morphology was directly related to the severity of inflammation (r = -0.74, p less than 0.01). Morphologic evidence of cellular injury to Langerhans cells was seen by electron microscopy in the majority of biopsies, although relatively few cells were affected in sodium lauryl sulphate and propylene glycol reactions. Benzalkonium chloride, unlike the other irritants, also induced a state of metabolic activation in a high proportion of epidermal Langerhans cells. Lymphocyte/Langerhans cell apposition was observed in most samples, but was particularly prevalent in the reactions to dithranol. The results of this study demonstrate that significant changes in the morphology and density of Langerhans cells occur in irritant contact dermatitis, some of which are directly influenced by the chemical nature of the irritant.