Development and validation of a measure for intention to adhere to HIV treatment.
We present the development and validation of a theory-derived scale measuring patients' behavioral intention to adhere to HIV care. Adherence to HIV care includes attendance at appointments and adherence to highly active antiretroviral therapy (HAART) regimens. These two components have been independently associated with long-term HIV outcomes. Items were chosen to reflect behavioral intention as defined by the Health Action Process Approach to health-seeking behavior. Items reflecting self-reported HIV knowledge were also included after expert panel review. The study took place from October 2009 to April 2010 at two HIV clinics in Houston, Texas. Participants were 287 adults with HIV/AIDS (10.1% female, mean age 50.8); 56.5% were African-American and 17% were Hispanic. Of the total, 87.1% were on HAART at enrollment. Factor analysis of survey items resulted in the retention of two domains, knowledge and intention, based on scree plot analysis of eigenvalues. Questions with factor loadings >0.4 were retained, yielding 4 knowledge questions and 10 intention questions. The survey had good internal consistency for knowledge (Cronbach's α=0.83) and for intention (Cronbach's α=0.81). In multivariate analysis, intention was associated with HIV viral suppression, defined as HIV-1 viral load <400 RNA copies/mL, (odds ratio [OR]=1.75, 95% .confidence interval [CI]=1.00-3.07). Knowledge was also associated with HIV suppression (OR=1.55, 95%, CI=1.09-2.12). The resulting study describes the development and preliminary validation of an HIV treatment-seeking intention measure. Additional studies are needed to validate this instrument in other populations.


Increased stroke risk in Bell's palsy patients without steroid treatment.
To investigate the risk of stroke development following a diagnosis of Bell's palsy in a nationwide follow-up study. Information on Bell's palsy and other factors relevant for stroke was obtained for 433218 eligible subjects without previous stroke who had ambulatory visit in 2004. Of those, 897 patients with Bell's palsy were identified. Over a median 2.9 years of follow-up, 4581 incident strokes were identified. We estimated hazard ratios (HR) and 95% confidence intervals [CI] with Cox proportional hazard models adjusting for age, sex, co-morbidities, and important risk factors. Standardized incidence ratio of stroke amongst patients with Bell's palsy was analyzed. Compared with non-Bell's palsy patients, patients with Bell's palsy had a 2.02-times (95% CI, 1.42-2.86) higher risk of stroke. The adjusted HR of developing stroke for patients with Bell's palsy treated with and without systemic steroid were 1.67 (95% CI, 0.69-4) and 2.10 (95%, 1.40-3.07), respectively. Patients with Bell's palsy carry a higher risk of stroke than the general population. Our data suggest that these patients might benefit from a more intensive stroke prevention therapy and regular follow-up after initial diagnosis.


miR-27a acts as an oncogene to regulate endometrial cancer progression by targeting USP46.
Endometrial cancer (EC) ranks as the fourth most common diagnosed cancer type in females worldwide. MicroRNAs (miRNAs) are important regulators with crucial roles in regulating diverse biologic processes, including tumor initiation and progression. Previous studies have demonstrated that miR-27a was correlated with the tumorigenesis of various cancers. However, its expression and biologic role in EC remain to be determined. This study aimed to clarify whether miR-27a acts as an oncogene in endometrial cancer (EC) by downregulating ubiquitin specific peptidase 46 (USP46). Expression of miR-27a was measured by qRT-PCR, and the results demonstrated that miR-27a was upregulated in EC cell lines compared to normal cell lines. Cell counting kit-8 (CCK-8) and wound-healing assays demonstrated that overexpression of miR-27a significantly promoted cell proliferation and migration. Online prediction algorithm and dual luciferase activity reporter assay revealed that USP46 acts as a direct target of miR-27a. USP46 expression was downregulated in EC cell lines during miR-27a overexpression. Collectively, our results indicated that miR-27a targets USP46 to promote EC cell proliferation and migration, suggesting an oncogene role of miR-27a in EC.


Prevalence, virulence factor genes and antibiotic resistance of Bacillus cereus sensu lato isolated from dairy farms and traditional dairy products.
B. cereus are of particular interest in food safety and public health because of their capacity to cause food spoilage and disease through the production of various toxins. The aim of this study was to determine the prevalence, virulence factor genes and antibiotic resistance profile of B. cereus sensu lato isolated from cattle grazing soils and dairy products in Ghana. A total of 114 samples made up of 25 soil collected from cattle grazing farm land, 30 raw milk, 28 nunu (yoghurt-like product) and 31 woagashie (West African soft cheese). Ninety-six B. cereus sensu lato isolates from 54 positive samples were screened by PCR for the presence of 8 enterotoxigenic genes (hblA, hblC, hblD, nheA, nheB, nheC, cytK and entFM), and one emetic gene (ces). Phenotypic resistance to 15 antibiotics were also determined for 96 B. cereus sensu lato isolates. About 72% (18 of 25 soil), 47% (14 of 30 raw milk), 35% (10 of 28 nunu) and 39% (12 of 31 woagashi) were positive for B. cereus sensu lato with mean counts (log10 cfu/g) of 4.2 ± 1.8, 3.3 ± 2.0, 1.8 ± 1.4 and 2.6 ± 1.8 respectively. The distribution of enterotoxigenic genes revealed that 13% (12/96 isolates) harboured all three gene encoding for haemolytic enterotoxin HBL complex genes (hblA, hblC and hblD), 25% (24/96 isolates) possessed no HBL gene, whereas 63% (60/96 isolates) possessed at least one of the three HBL genes. All three genes encoding for non-haemolytic enterotoxin (nheA, nheB and nheC) were detected in 60% (57/96) isolates, 14% (13/96) harboured only one gene, 19% (18/96) whereas 8% possessed none of the NHE genes. The detection rates of cytk, entFM, and ces genes were 75, 67 and 9% respectively. Bacillus cereus s. l. isolates were generally resistant to β-lactam antibiotics such as ampicillin (98%), oxacillin (92%), penicillin (100%), amoxicillin (100%), and cefepime (100%) but susceptible to other antibiotics tested. Bacillus cereus s. l. is prevalent in soil, raw milk and dairy products in Ghana. However, loads are at levels considered to be safe for consumption. Various enterotoxin genes associated with virulence of B. cereus are widespread among the isolates.


Estimates of water and solute release from a coal waste rock dump in the Elk Valley, British Columbia, Canada.
Long term (1999 to 2014) flow and water quality data from a rock drain located at the base of a coal waste rock dump constructed in the Elk Valley, British Columbia was used to characterize the release of three solutes (NO3-, Cl- and SO42-) from the dump and obtain whole dump estimates of net percolation (NP). The concentrations of dump derived solutes in the rock drain water were diluted by snowmelt waters from the adjacent natural watershed during the spring freshet and reached a maximum concentration during the winter baseflow period. Historical peak baseflow concentrations of conservative ions (NO3- and Cl-) increased until 2006/07 after which they decreased. This decrease was attributed to completion of the flushing of the first pore volume of water stored within the dump. The baseflow SO42- concentrations increased proportionally with NO3- and Cl- to 2007, but then continued to slowly increase as NO3- and Cl- concentrations decreased. This was attributed to ongoing production of SO42- due to oxidation of sulfide minerals within the dump. Based on partitioning of the annual volume of water discharged from the rock drain to waste rock effluent (NP) and water entering the rock drain laterally from the natural watershed, the mean NP values were estimated to be 446±50mm/a (area normalized net percolation/year) for the dump and 172±71mm/a for the natural watershed. The difference was attributed to greater rates of recharge in the dump from summer precipitation compared to the natural watershed where rainfall interception and enhanced evapotranspiration will increase water losses. These estimates included water moving through subsurface pathways. However, given the limitations in quantifying these flows the estimated NP rates for both the natural watershed and the waste rock dump are considered to be low, and could be much higher (e.g. ~450mm/a and ~800mm/a).


Going smoke-free: attitudes of mental health professionals to policy change.
WHAT IS KNOWN ON THE SUBJECT?: While smoking rates within the general population in Australia are dropping, 32% of Australians with a mental illness smoke, increasing to 73% among those with severe or chronic mental illness. In Australia and elsewhere, smoking bans within mental health facilities have been implemented. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: We surveyed 98 mental health professionals in Australia to gather information on attitudes toward smoke-free policies in mental health/psychiatric units within Australia. While previous research has sought information on agreement or disagreement with smoking-bans, very little research has been conducted focusing on attitudes held by mental health professionals towards smoke-free policies. This study utilized a mixed-methods approach in which the qualitative data provides a rich source of information to assist in developing programmes or interventions to influence attitudes and therefore change behaviours of mental health professionals. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: This paper can be useful in providing a better understanding of the theories linking smoking and mental illness, and the common 'myths' which influence attitudes to smoking cessation in clinical populations. Results will influence the development of training and education resources for mental health practitioners, and particularly for nursing staff working within psychiatric facilities, in relation to smoking cessation. Importantly, this issue has implications in the areas of policy planning and development, education relating to smoking behaviour and smoking cessation programmes, together with holistic health care. Introduction Mental health units in Australia and internationally are increasingly implementing smoke-free policies. Due to the high prevalence of smoking among clinical populations, this has become an important research area. Purpose of study This study explored the attitudes of mental health professionals toward smoke-free policies in mental health units within Australia. Method Using an online survey design, 98 Australian mental health professionals participated in the study. Results Results indicated that only 25.5% agreed with a total smoking ban. Although supporting smoke-free initiatives within the wider community, participants commonly held attitudes that were unsupportive of smoking bans, and indicated beliefs inconsistent with a smoke-free policy for clinical populations. Discussion Results suggest the need for appropriate staff education and training regarding smoking behaviours and risks, and smoking cessation treatments for clinical populations if smoke-free policies are to be successfully implemented. Implications for practice Findings suggest important implications for holistic mental health care, staff education and training, as well as policy, planning and development, particularly in relation to this treatment group, who are likely to have entered a psychiatric unit in crisis.


Rapid repair of rat sciatic nerve injury using a nanosilver-embedded collagen scaffold coated with laminin and fibronectin.
Scaffold with micro-channels has shown great promise in facilitating axonal regeneration after peripheral nerve injury. Significant research has focused on mimicking, in terms of composition and function, the ability of the basement membrane of Schwann cells to both promote and guide axonal regeneration. We aim to investigate the ability of a tissue-engineered scaffold with nanosilver and collagen to adsorb laminin and fibronectin, and the usefulness of this scaffold for repairing and regenerating a 10-mm peripheral nerve gap in rats. In this study, nanosilver-embedded collagen scaffolds were prepared and coated with laminin (LN) or LN plus fibronectin (FN). Scanning electron microscopy of the transverse and longitudinal sections of the scaffold revealed axially oriented microtubules ranging from 20 to 80 µm in diameter, and the internal surface of microtubules was found to be evenly coated with LN and FN. Energy dispersive spectrometry also confirmed an even distribution of nanosilver particles within the scaffold. To test its effectiveness in restoring neuronal connection, the scaffold was used in order to bridge 10 mm gaps in the severed sciatic nerve of rats. The rats were divided into an experimental group (receiving scaffold coated with LN and FN), a control group (receiving scaffold coated with LN only) and an autologous graft group. The functional recovery 40 days after surgery was examined by electrophysiology and sciatic nerve functional index (SFI) evaluation. FluoroGold™ (FG) retrograde tracing, toluidine blue staining and transmission electron microscopy were also used to examine the regenerated nerve fibers and to establish their myelination status. The experimental group displayed partially restored nerve function. The recovery was comparable to the effect of autologous nerve graft and was better than that observed in the control group. A better functional recovery correlated with more FG-labeled neurons, higher density of toluidine blue stained nerve fibers and thicker myelin sheath. Our results demonstrated that nanosilver-embedded collagen scaffolds with LN and FN coating is effective in aiding axonal regeneration, and recovery is comparable to the effect of an autologous nerve graft.


Encapsulation of a Water Molecule inside C60 Fullerene: The Impact of Confinement on Quantum Features.
We introduce an efficient quantum fully coupled computational scheme within the multiconfiguration time-dependent Hartree (MCTDH) approach to handle the otherwise extremely costly computations of translational-rotational-vibrational states and energies of light-molecule endofullenes. Quantum calculations on energy levels are reported for a water molecule inside C60 fullerene by means of such a systematic approach that includes all nine degrees of freedom of H2O@C60 and does not consider restrictions above them. The potential energy operator is represented as a sum of natural potentials employing the n-mode expansion, along with the exact kinetic energy operator, by introducing a set of Radau internal coordinates for the H2O molecule. On the basis of the present rigorous computations, various aspects of the quantized intermolecular dynamics upon confinement of H2O@C60 are discussed, such as the rotational energy level splitting and the significant frequency shifts of the encapsulated water molecule vibrations. The impact of water encapsulation on quantum features is explored, and insights into the nature of the underlying forces are provided, highlighting the importance of a reliable first-principles description of the guest-host interactions.


Clinical Significance of Peritoneal Fluid Examination for Free Cancer Cells in Patients Qualified for Surgery for Gastric Cancer.
Background: Peritoneal lavage cytology in patients with gastric cancer may correlate with an unfavorable prognosis. This study evaluated the presence of free cancer cells in the peritoneal lavage of a population of patients with gastric cancer and its correlation with the outcome of surgical treatment. Methods: One hundred patients diagnosed with gastric or gastrointestinal junction adenocarcinoma underwent surgery. In all patients, a cytological and immunohistochemical analysis of peritoneal lavage was performed. Based on the presence of free cancer cells (fcc) at the cytological and immunohistochemical examination of peritoneal lavage, patients undergoing surgery for gastric cancer were divided into two groups: fcc (+) and fcc (-). Results: A total of 100 patients, 37 women, and 63 men with a median age of 65 years were included in the study. In the entire study group, 16 (16%) patients were positive for the presence of free cancer cells (fcc +) at peritoneal lavage examination. However, in the group of patients who underwent gastrectomy, fcc (+) was found in 10 out of 77 (13%) patients. The presence of cancer cells in peritoneal lavage was a strong predictive factor in an unfavorable outcome after surgery, and 1-year and 2-year patient survival was 34 and 0% in fcc (+) patients and 79 and 59% in fcc (-), respectively. Moreover, the presence of free cancer cells was associated with a five-fold increased risk of death within 2 years after surgery. When analyzing the group of patients undergoing R0/R1 surgery, this difference was even more significant (p < 0.0001). Conclusions: The presence of free cancer cells in peritoneal lavage may significantly affect the outcome of patients with gastric cancer. Radical surgery in patients with free cancer cells in the peritoneal lavage did not result in a survival advantage. Identification of free cancer cells could help for a better stratification of gastric cancer patients, identifying those patients who could better benefit from a radical surgical treatment, finally improving long-term survival.


[Between 'sickness' and 'illness': from socialization to individualization of the 'disease'].
In biomedicine, psychiatry and psychoanalysis, there are not sicknesses but rather individual illnesses. If medical anthropology takes for granted the universality of this Western medical, cultural axiom, it will hardly be able to understand traditional conceptions of sickness, which do not separate what is individual from what is social in pathological and therapeutic processes. One of the main tasks of contemporary medical anthropology is to discover the devices and processes that connect these two spheres--the states of health of the person's body and of the social body/group of which he is a part--through the origin, development and experience of illness. To do this, the distinctive properties of sickness as an event must be defined: its individual selectivity and social reactivity; its recurrence and reversibility; its individual and collective history as a singular event or as a 'pathotype' that, by means of bodily or material 'memorials', is part of the pathohistory of the sick person and of his group; its social recessiveness; and its interconnections with other types of ill. In traditional societies, individual ills are, through magico-religious interpretations, converted into social disorder. Each referent (divinity, ancestor, magic, witchcraft, etc.) of such interpretations is a cognitive, subjective and social entity that activates the individual through the social, and the social through the individual, by bringing into play the interpretors' personal and collective strategies. Magico-religious interpretations of illness rely on psychic processes of projection and persecution. Contrary to biomedicine, traditional practices activate, shape and legitimate the universal propensity of the sick to expel ills from inside and to locate their outside, either in an invisible or a human being. In African societies, persecutive interpretations are not only normal, frequent and legitimate but also normative since they underlie the various social or political uses to which illness is put. Persecutive communication is the process by which an individual trouble, ill or woe is converted into social disorder. This intersubjective process cannot be defined without distinguishing explanations from interpretations of illness. The latter are metacommunicative acts by which the sick person's 'social partners' use his illness to promote their own strategies. Healing the patient is the obvious issue in persecutive communication, but its hidden stakes are how to define, face and settle the various social conflicts that indwell the group.(ABSTRACT TRUNCATED AT 400 WORDS)


Supragingival plaque removal with and without dentifrice: a randomized controlled clinical trial.
The aim of this study was to compare the efficacy of dental plaque removal by brushing with and without conventional dentifrice. Twenty-four students aged 17 to 28 years participated in this randomized controlled clinical trial. Quadrants 1-3 or 2-4 were randomly allocated to the test group (brushing without dentifrice) or control group (brushing with dentifrice). After 72 h of cessation of oral hygiene, Quigley & Hein (Turesky) plaque index was assessed before and after brushing by a calibrated and blind examiner. Overtime and intergroup comparisons were performed by Student's paired sample t-test at 5% significance level. The results showed that both groups after toothbrushing presented statistically significant reductions in plaque, with no differences between them (from 3.06 ± 0.54 to 1.27 ± 0.26 versus from 3.07 ± 0.52 to 1.31 ± 0.23). A separate analysis of the buccal and lingual aspects also showed no significant differences between groups. It may be concluded that the use of a conventional dentifrice during toothbrushing does not seem to enhance plaque removal capacity.


Institution of a Novel Process for N95 Respirator Disinfection with Vaporized Hydrogen Peroxide in the Setting of the COVID-19 Pandemic at a Large Academic Medical Center.
Personal protective equipment (PPE) has been an invaluable yet limited resource when it comes to protecting healthcare workers against infection during the 2019 coronavirus (COVID-19) pandemic. In the US, N95 respirator supply chains are severely strained and conservation strategies are needed. A multidisciplinary team at the Washington University School of Medicine, Barnes Jewish Hospital, and BJC Healthcare was formed to implement a program to disinfect N95 respirators. The process described extends the life of N95 respirators using vaporized hydrogen peroxide (VHP) disinfection and allows healthcare workers to retain their own N95 respirator across a large metropolitan healthcare system.


Spectrin regulates cell contractility through production and maintenance of actin bundles in the Caenorhabditis elegans spermatheca.
Disruption to the contractility of cells, including smooth muscle cells of the cardiovascular system and myoepithelial cells of the glandular epithelium, contributes to the pathophysiology of contractile tissue diseases, including asthma, hypertension, and primary Sjögren's syndrome. Cell contractility is determined by myosin activity and actomyosin network organization and is mediated by hundreds of protein-protein interactions, many directly involving actin. Here we use a candidate RNA interference screen of more than 100 Caenorhabditis elegans genes with predicted actin-binding and regulatory domains to identify genes that contribute to the contractility of the somatic gonad. We identify the spectrin cytoskeleton composed of SPC-1/α-spectrin, UNC-70/β-spectrin, and SMA-1/β heavy-spectrin as required for contractility and actin organization in the myoepithelial cells of the C. elegans spermatheca. We use imaging of fixed and live animals as well as tissue- and developmental-stage-specific disruption of the spectrin cytoskeleton to show that spectrin regulates the production of prominent central actin bundles and is required for maintenance of central actin bundles throughout successive rounds of stretch and contraction. We conclude that the spectrin cytoskeleton contributes to spermathecal contractility by promoting maintenance of the robust actomyosin bundles that drive contraction.


Initial and midterm results of the Bolton Relay Thoracic Aortic Endovascular Pivotal Trial.
To report the initial and midterm results of the Bolton Relay Thoracic Stent Graft for the endovascular treatment of thoracic aortic lesions [thoracic endovascular aortic repair (TEVAR)]. The Bolton Relay Thoracic Aortic Endovascular Pivotal Trial was a prospective, nonrandomized, multicenter, U.S. Investigational Device Exemption study conducted at 27 U.S. investigational sites. One hundred twenty TEVAR subjects were treated with the Relay device between January 2007 and May 2010, with 13 patients enrolled during the continued access phase through September 2012. TEVAR outcomes were compared with a prospectively and retrospectively enrolled surgical cohort consisting of 60 patients enrolled under similar inclusion/exclusion criteria. Follow-up examinations were prescribed at 1 month, 6 months, and yearly thereafter for 5 years. Major adverse events (MAEs) included stroke, paralysis/paraplegia, myocardial infarction, procedural bleeding, respiratory failure, renal failure, wound healing complications, and aneurysm-related mortality. Stent grafts were successfully delivered and deployed in 129 of 133 patients (97.0%). At 30 days, a lower rate of mortality was observed in the TEVAR arm (5.3% vs 10.0%; P = .230), and TEVAR was associated with a significantly lower rate of MAEs (20.3% vs 48.3%; P < .001), primarily driven by a lower frequency of respiratory failure in the cohort (5.5% vs 21.6%; P = .007) and procedural bleeding. Freedom from aneurysm-related mortality through 5 years was similar at 91.3% for the TEVAR cohort and 89.4% for the surgical cohort (P = .406); with 5-year freedom from all-cause mortality at 57.1% and 50.2% (P = .289), respectively. Freedom from MAEs through 5 years was significantly higher in the TEVAR cohort (65.7% vs 44.7%; P = .001). Six TEVAR patients (4.5%) experienced core laboratory-reported type I or III endoleaks, and secondary procedures were performed in 10 patients (7.5%), with seven procedures to correct endoleak and one surgical conversion. Endograft migration occurred in three patients (2.3%) and wireform fractures were assessed in two patients (1.5%). Aneurysm sac size decreased or remained stable in 113 patients (85.0%) over 5-year follow-up. There were no instances of rupture or endograft occlusion. A 38-subject subset treated with the newer Relay Plus Delivery System had a significantly reduced MAE rate (15.8% vs 35.8%; P = .035), and fewer perioperative strokes (2.6% vs 12.6%; P = .108). Data from the Relay TEVAR clinical trial demonstrate safety and effectiveness of the Relay device compared with surgical controls, indicating continued device durability with a low rate of device-related complications through 5 years.


Sex-dependent and chronic alterations in behavior and mitochondrial function in a rat model of pediatric mild traumatic brain injury.
To determine if chronic changes in mitochondrial function occur following a mild traumatic brain injury in young rats. Closed-head, weight drop model was used to cause mTBI by applying rotational forces to the brain without surgery. Behavioral battery was used to assess multiple dimensions of impairment across time. Analysis of brain tissue carried out at three-weeks post-injury represents a chronic time point to complement previous work examining acute time points. Twenty-three male and 22 female rats one month of age were divided equally into sham and mTBI groups with the latter undergoing the weight drop. Multiple behavioral tests in combination with energetic (oxygen consumption), molecular (immunoblotting), and imaging (electron microscopy) characterization of brain mitochondria were performed. Mitochondria isolated from sham juvenile female rats had higher basal oxygen consumption compared to juvenile male rats (514.875 ± 171.091 pmol/min vs. 267 ± 73.906 pmol/min, p < 0.0001). Chronic sex-dependent differences were observed in females after mTBI in basal (514.875 ± 171.091 pmol/min vs. 600.688 ± 124.422 pmol/min, p = 0.0264) and maximal oxygen consumption (298.938 ± 119.964 pmol/min vs. 403.281 ± 112.922 pmol/min, p = 0.0001) and proton leak (59.46 ± 7.807 vs. 84.32 ± 5.80 pmol/min, p = 0.0001). The juvenile rat brain displays sex differences in mitochondrial function at (1) baseline and (2) in long-term outcomes after mTBI. These results offer new insight into a potential mechanism for persistent, individualized impairments following pediatric mTBI.


Clinical relevance of rhinovirus infections among adult hospitalized patients.
Human rhinovirus (HRV) is an emerging viral pathogen. To characterize a group of patients admitted due to infection by this agent in a general hospital in Chile. Cases were identified by RT-PCR for 1 year through active surveillance of patients admitted with severe respiratory illness. Diagnosis was not available during hospitalization. Thirty-two cases were identified, 90% were ≥60 years old or had co-morbid conditions. Human rhinovirus-related admissions represented 23.7% of hospitalization due to severe acute respiratory infections among adults and ranked second to influenza (37.8%). Patients presented with pneumonia (68.8%), decompensated chronic lung conditions (21.9%), heart failure or influenza-like illness (6.3% each). Admission to intensive or intermediate care units was required by 31.2% and in-hospital mortality reached 12.5%. A CURB-65 score ≥3 was significantly associated to in-hospital mortality (p<0.05). Most patients received antibiotics (90%). Human rhinovirus infections in elderly patients with co-morbid conditions are associated with hospitalizations, requiring critical or semi-critical antibiotics use. A high CURB-65 score was associated to in-hospital mortality.


Precesarean Prophylactic Balloon Catheters for Suspected Placenta Accreta: A Randomized Controlled Trial.
To examine the effect of prophylactic balloon catheters on bleeding morbidity among women with a prenatal diagnosis of placenta accreta. In a randomized trial, women with a prenatal diagnosis of placenta accreta were randomized to either preoperative prophylactic balloon catheters (intervention group) or to a control group. Other than placement of the prophylactic balloon catheters in the anterior division of the internal iliac arteries, the same multidisciplinary approach was used in both groups. The primary study outcome was the number of packed red blood cell (RBC) units transfused. To detect a mean reduction of three packed RBC units with the prophylactic balloon catheters, 12 women in each group were needed. Between January 2009 and March 2015, 27 women were randomized: 13 in the intervention group and 14 in the control group. Demographic and obstetric characteristics were similar between the groups. Six (46.2%) women in the intervention and seven (50.0%) in the control group underwent cesarean hysterectomy (P=.84). There were no significant differences between the intervention and control groups in the mean number of packed RBC units transfused, 5.2 (±6.2) and 4.1 (±3.8), respectively (P=.90), or in the calculated blood loss, 4,950 (±5,051) and 4,709 (±3,434) mL (P=.72). The number of women with blood loss greater than 2,500 mL, number of plasma products transfused, duration of surgery, peripartum complications, and hospitalization length did not differ significantly between the groups. Reversible adverse effects related probably to prophylactic balloon catheter insertion were noted in 2 of 13 (15.4%) women. In women with preoperative suspicion of placenta accreta, preoperative placement of prophylactic balloon catheters did not affect the number of packed RBC units transfused. ClinicalTrials.gov, www.clinicaltrials.gov, NCT01373255. I.


General and Stereoselective Method for the Synthesis of Sterically Congested and Structurally Diverse P-Stereogenic Secondary Phosphine Oxides.
A general and efficient method for the synthesis of bulky and structurally diverse P-stereogenic chiral secondary phosphine oxides (SPOs) by using readily available chiral amino alcohol templates is described. These chiral SPOs could be used as chiral building blocks for the synthesis of difficult-to-access bulky P-stereogenic phosphine compounds or ligands for organic catalysis.


Organisation and promoter activity of the retinoic-acid-induced-heparin-binding (RIHB) gene.
The heparin-binding protein, RIHB, is encoded by a gene that is expressed temporarily during the early period of chicken embryogenesis. We have now isolated genomic clones of the chicken RIHB gene, determined its transcription initiation sites, characterized its promoter region and established the functional activity of the RIHB gene promoter. The 5' flanking region and the beginning of the first exon revealed a structural organisation characteristic of housekeeping and growth-control-related genes. It lacked canonical TATA or CAAT boxes but contained several GC boxes. The structure of the RIHB gene is compared with those of the human and mouse midgestation kidney (MK) genes. In the coding exons, the similarities between the three genes are striking. In contrast, the structure and location of the first non-coding exon is different. Analysis of the promoter activity suggests an indirect regulation of transcription by retinoic acid and demonstrates a high degree of complexity of the regulation of the RIHB gene.


Meta-omics integration approach reveals the effect of soil native microbiome diversity in the performance of inoculant Azospirillum brasilense.
Plant growth promoting bacteria (PGPB) have been used as integrative inputs to minimize the use of chemical fertilizers. However, a holistic comprehension about PGPB-plant-microbiome interactions is still incipient. Furthermore, the interaction among PGPB and the holobiont (host-microbiome association) represent a new frontier to plant breeding programs. We aimed to characterize maize bulk soil and rhizosphere microbiomes in irradiated soil (IS) and a native soil (NS) microbial community gradient (dilution-to-extinction) with Azospirillum brasilense Ab-V5, a PGPB commercial inoculant. Our hypothesis was that plant growth promotion efficiency is a result of PGPB niche occupation and persistence according to the holobiont conditions. The effects of Ab-V5 and NS microbial communities were evaluated in microcosms by a combined approach of microbiomics (species-specific qPCR, 16S rRNA metataxonomics and metagenomics) and plant phenomics (conventional and high-throughput methods). Our results revealed a weak maize growth promoting effect of Ab-V5 inoculation in undiluted NS, contrasting the positive effects of NS dilutions 10-3, 10-6, 10-9 and IS with Ab-V5. Alpha diversity in NS + Ab-V5 soil samples was higher than in all other treatments in a time course of 25 days after sowing (DAS). At 15 DAS, alpha diversity indexes were different between NS and IS, but similar in all NS dilutions in rhizospheric samples. These differences were not persistent at 25 DAS, demonstrating a stabilization process in the rhizobiomes. In NS 10-3 +Ab-V5 and NS 10-6 Ab-V5, Ab-V5 persisted in the maize rhizosphere until 15 DAS in higher abundances compared to NS. In NS + Ab-V5, abundance of six taxa were positively correlated with response to (a)biotic stresses in plant-soil interface. Genes involved in bacterial metabolism of riboses and amino acids, and cresol degradation were abundant on NS 10-3 + Ab-V5, indicating that these pathways can contribute to plant growth promotion and might be a result of Ab-V5 performance as a microbial recruiter of beneficial functions to the plant. Our results demonstrated the effects of holobiont on Ab-V5 performance. The meta-omics integration supported by plant phenomics opens new perspectives to better understanding of inoculants-holobiont interaction and for developing better strategies for optimization in the use of microbial products.


Group psychoeducation as treatment for psychological nonepileptic seizures.
There is no consensus for the type(s) of treatment(s) that may be effective or ineffective for psychological nonepileptic seizures (PNES). We provided an open-ended group psychotherapy program to 10 patients with PNES, including a disorder-specific psychoeducation treatment component in the first 10 weeks. Seizure frequency and questionnaire responses were examined pre- and posttreatment in all 7 of 10 individuals who completed the majority of the psychoeducational sessions. Four individuals experienced no change in seizure frequency; in three of these this was due to a cessation of events at treatment initiation. Two individuals experienced a decline; and one, an increase, in seizure frequency. Significant decreases were reported in posttraumatic (P=0.003) and dissociative (P=0.04) symptoms and emotionally based coping mechanisms (P=0.03). There was also a trend toward improved quality of life (P=0.07). Experience/expression of anger remained stable. Psychoeducation may be an effective method of treating PNES and may improve coping strategies and reduce PNES-associated psychopathology in some patients. Additional controlled studies on larger samples are needed.


Pharmaceutical development of an oral tablet formulation containing a spray dried amorphous solid dispersion of docetaxel or paclitaxel.
Previously, it was shown in Phase I clinical trials that solubility-limited oral absorption of docetaxel and paclitaxel can be drastically improved with a freeze dried solid dispersion (fdSD). These formulations, however, are unfavorable for further clinical research because of limitations in amorphicity of SD and scalability of the production process. To resolve this, a spray drying method for an SD (spSD) containing docetaxel or paclitaxel and subsequently drug products were developed. Highest saturation solubility (Smax), precipitation onset time (Tprecip), amorphicity, purity, residual solvents, yield/efficiency and powder flow of spSDs were studied. Drug products were monitored for purity/content and dissolution during 24 months at +15-25°C. Docetaxel spSD Smax was equal to that of fdSD but Tprecip was 3 times longer. Paclitaxel spSD Smax was 30% increased but Tprecip was equal to fdSD. spSDs were fully amorphous, >99% pure, <5% residual solvents, mean batch yield was 100g and 84%. spSDs had poor powder flow characteristics, which could not be resolved by changing settings, but by using 75% lactose as diluent. The drug product was a tablet with docetaxel or paclitaxel spSD and was stable for at least 24 months. Spray drying is feasible for the production of SD of docetaxel or paclitaxel for upcoming clinical trials.


Future Directions in Research in Transcriptomics in the Healing of Diabetic Foot Ulcers.
Diabetic foot ulcers are a health crisis that affect millions of individuals worldwide. Current standard of care involves diligent wound care with adjunctive antibiotics and surgical debridement. However, despite this, the majority will still become infected and fail to heal. Recent efforts using bioengineered skin initially appeared promising, but randomized clinical trials have disappointed. Scientists have now begun to understand that the normal wound healing physiology does not apply to diabetic foot ulcers as they maintain a chronic state of inflammation and fail to progress in a linear pathway. Using transcriptomics, research over the past decade has started identifying master genes and protein pathways that are dysregulated in patients with diabetes. This review paper discusses those genes involved and how novel advancements are using this information to create new biologically based compounds to accelerate wound healing in patients with diabetic foot ulcers.


Patterns of Early-Life Social and Environmental Exposures and Child Cognitive Development, Rhea Birth Cohort, Crete, Greece.
Early-life exposures are critical for later child cognitive development. McCarthy Scales of Children's Abilities (MSCA) were used to assess cognitive development of 700 preschoolers (Mage = 4.2 years), derived from the "Rhea" birth cohort, in Greece. Principal component analysis (PCA) was applied on prospectively collected exposure data. Six components were extracted; five of them were associated with child cognition. Higher parental social status, preschool attendance and less TV watching, nonsmoking during pregnancy and breastfeeding, and parental involvement in child life were protective factors of child cognition at 4 years. Increased child birth order was negatively associated with child cognition. Offspring's size at birth was not associated with any cognitive outcome. These findings reveal the importance of early-life exposures to child cognitive development.


Susceptibility to Food Advertisements and Sugar-Sweetened Beverage Intake in Non-Hispanic Black and Non-Hispanic White Adolescents.
Obesity among adolescents in the United States has risen by 16% in the past 30 years. One important contributing factor may be the increased consumption of sugar sweetened beverages (SSBs), which is encouraged by advertisements for unhealthy foods and drinks that are targeted to adolescents. The purpose of this analysis was to determine the association between susceptibility to food and drink advertisements and sugar-sweetened beverage (SSB) consumption in non-Hispanic black (NHB) and non-Hispanic white (NHW) adolescents and to examine if BMI is associated with SSB consumption. Data were obtained from 765 NHB and NHW of ages 14-17 who were surveyed in the Family Life, Activity, Sun, Health, and Eating study sponsored by the National Cancer Institute. Two weighted adjusted logistic regression models were conducted. The first examined the associations of advertisement susceptibility, race, and BMI with SSB consumption. The second examined the associations of race and BMI with advertisement susceptibility. Adolescents with high advertisement susceptibility were more likely to consume at least one SSB daily (OR 1.73, 95% CI 1.21, 2.47). Additionally, non-Hispanic blacks were more likely to consume at least one SSB daily (OR 1.75, 95% CI 1.08, 2.85) and more likely to be highly susceptible to advertisements (OR 1.72, 95% CI 1.19, 2.48) than non-Hispanic whites. No significant associations were found between BMI and advertising susceptibility or BMI and daily SSB consumption. One approach to addressing the consumption of SSBs may be to reduce advertising that markets unhealthy food and beverages to adolescents and minorities.


East/Central/South African Genotype in a Chikungunya Outbreak, Dhaka, Bangladesh, 2017.
In 2017, an unprecedented increase in febrile illness was observed in Dhaka, Bangladesh. Real-time reverse transcription PCR confirmed that 603 (40.2%) of 1,500 cases were chikungunya fever. Phylogenetic analysis revealed circulation of the non-A226V East/Central/South African genotype of chikungunya virus in Bangladesh.


Total pericardiectomy for chronic constrictive pericarditis using femoro-femoral bypass.
A technique of total pericardiectomy for chronic constrictive pericarditis is presented. The authors have used a femoro-femoral cardiopulmonary bypass in nine cases of constrictive pericarditis to prevent the complications of the traditional approach. The advantages of this technique in comparison to the performance of pericardiectomy without the use of extracorporeal circulation (ECC) or with standard ECC are discussed.


Identification of prognostic risk factors for esophageal adenocarcinoma using bioinformatics analysis.
Esophageal adenocarcinoma (EAC) is the most common type of esophageal cancer in Western countries. It is usually detected at an advanced stage and has a poor prognosis. The aim of this study was to identify key genes and miRNAs in EAC. The mRNA microarray data sets GSE1420, GSE26886, and GSE92396 and miRNA data set GSE16456 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were obtained using R software. Functional enrichment analysis was performed using the DAVID database. A protein-protein interaction (PPI) network and functional modules were established using the STRING database and visualized by Cytoscape. The targets of the DEMs were predicted using the miRecords database, and overlapping genes between DEGs and targets were identified. The prognosis-related overlapping genes were identified using Kaplan-Meier analysis and Cox proportional hazard analysis based on The Cancer Genome Atlas (TCGA) database. The differential expression of these prognosis-related genes was validated using the expression matrix in the TCGA database. Seven hundred and fifteen DEGs were obtained, consisting of 313 upregulated and 402 downregulated genes. The PPI network consisted of 281 nodes; 683 edges were constructed and 3 functional modules were established. Forty-four overlapping genes and 56 miRNA- mRNA pairs were identified. Five genes, FAM46A, RAB15, SLC20A1, IL1A, and ACSL1, were associated with overall survival or relapse-free survival. FAM46A and IL1A were found to be independent prognostic indicators for overall survival, and FAM46A, RAB15, and SLC20A1 were considered independent prognostic indicators for relapse-free survival. Among them, the overexpression of RAB15 and SLC20A1 and lower expression of ACSL1 were also identified in EAC tissues based on the expression matrix in the TCGA database. These prognosis-related genes and differentially expressed miRNA have provided potential biomarkers for EAC diagnosis and treatment.


CLINICAL FEATURES OF 15 PATIENTS UNDER SURVEILLANCE FOR RENAL MASSES.
(Objective) We investigated the clinical features of patients under surveillance for localized renal masses. (Methods) This study was a retrospective analysis of 15 patients who were diagnosed as having clinically localized renal cell carcinoma and were placed under surveillance and 68 patients who underwent immediate radical operation for renal masses. (Results) The age at diagnosis in the surveillance group was significantly higher than in the immediate operation group (median, 81 vs. 65 years, respectively, P<0.01). The Charlson Comorbidity Index in the surveillance group was significantly higher than in the immediate operation group (median, 5 vs. 2, respectively, P<0.01) and 10 patients (67%) had complications, which was one of the reasons for surveillance. The median initial tumor size in the surveillance group was 2.5 cm (1.5-10.1). There was no significant difference in the tumor size between the two groups. During a median follow-up of 19 months (6-55) the median tumor growth rate was 0.29 cm per year (-0.19-0.65) in the surveillance group. Of the 15 patients with computed tomography follow-up, four underwent surgical resection of the renal masses after surveillance. The histological diagnosis was clear cell renal cell carcinoma in all four. During follow-up, two patients died of other causes and one patient had bone metastasis but there was no death related to the renal masses in the surveillance group. (Conclusions) The appropriateness of the surveillance should be considered when we initiate surveillance for patients with renal masses because metastasis was detected in one patient in this study. On the other hand, surveillance may be an acceptable management method for elderly or severely comorbid patients because there were two deaths from other causes in the surveillance group.


Occupational Exposure to Diesel Motor Exhaust and Lung Cancer: A Dose-Response Relationship Hidden by Asbestos Exposure Adjustment? The ICARE Study.
Background. In a French large population-based case-control study we investigated the dose-response relationship between lung cancer and occupational exposure to diesel motor exhaust (DME), taking into account asbestos exposure. Methods. Exposure to DME was assessed by questionnaire. Asbestos was taken into account through a global indicator of exposure to occupational carcinogens or by a specific JEM. Results. We found a crude dose response relationship with most of the indicators of DME exposure, including with the cumulative exposure index. All results were affected by adjustment for asbestos exposure. The dose response relationships between DME and lung cancer were observed among subjects never exposed to asbestos. Conclusions. Exposure to DME and to asbestos is frequently found among the same subjects, which may explain why dose-response relationships in previous studies that adjusted for asbestos exposure were inconsistent.


Prevalence of dyslipidaemia in OSA patients at a tertiary care center.
Background Obstructive sleep apnea (OSA) is associated with many diseases, but evidence indicating that OSA is a risk factor for dyslipidemia is lacking. Aim This cross-sectional study investigated the prevalence of lipid abnormalities in patients with OSA and its association with OSA severity. In this cross-sectional study, 102 patients with suspected OSA underwent standard polysomnography. All patients with an apnea-hypopnea index (AHI) of ≥5 with symptoms were diagnosed as having OSA. A fasting blood sample was collected from all patients. Blood levels of triglycerides (TGs), total cholesterol (TC), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL) were measured. The relationship between the AHI and lipid profiles was analyzed, and linear regression analysis was performed to evaluate the effect of dyslipidemia on OSA. The patients with OSA had a significantly higher TG level and a significantly lower HDL level than did those without OSA. The lipid abnormalities increased with OSA severity. The mean serum TG level was higher in the severe OSA group (175±46.5 vs. 153±42.45, mg/dl P = 0.048), and the mean serum HDL level was lower in the severe OSA group (38.43 ± 5.19 vs. 45.73 ± 4.98, mg/dl P = 0.004). Serum TG, cholesterol, and LDL levels were correlated with a BMI of <30 and a BMI of >30 in the OSA group. Linear regression analysis indicated that only age (β = 0.301, P = 0.000), BMI (β = 0.455, P = 0.000), serum HDL level (β = -0.297, P = 0.012), and serum LDL level (β = 0.429, P = 0.001) were the independent predictors of OSA. OSA and obesity are potential risk factors for dyslipidemia. The diagnosis of hyperlipidemia was linked to OSA, and the association was more significant with OSA severity. Hyperlipidemia was well recognized in patients with OSA. LDL and HDL are the independent predictors of OSA.


Skin regeneration after chemical burn under the effect of taxifolin-based preparations.
We studied the effect of liposome preparation containing taxifolin oligomers and taxifolin conjugates with carbonyl compounds on skin regeneration after chemical burn. The preparations containing flavonoid conjugates intensified regeneration processes and reparation of hair follicles and sebaceous glands after chemical burn. The preparation based on taxifolin conjugate with acetaldehyde was most effective; its activity was comparable with that of the wound-healing preparation Olasol. Taxifolin conjugates with carbonyl compounds can be used for the creation of combined wound- and burn-healing preparations.


Biology and management of hemp russet mite (Acari: Eriophyidae).
Hemp is rapidly becoming a crop of global agricultural importance, and one of the more serious pests of this crop is hemp russet mite (HRM) Aculops cannabicola (Acari: Eriophyidae). Significant knowledge gaps presently exist regarding critical aspects of pest biology, quantification of crop damage, and efficacy of pesticides. Here we assessed the role of cannabidiol (CBD) on HRM performance, efficacy of sulfur treatments in field trials, and effect of hot water immersion with and without surfactants in reducing HRM counts on hemp cuttings. We found that HRM fecundity was reduced on a high-CBD cultivar compared with a low-CBD cultivar in detached leaf assays. In contrast, HRM fecundity and survival were not impacted when reared on high-CBD diet in artificial feeding assays. This suggests that cannabinoids other than CBD may aid in reduction of mite populations on the high-CBD cultivar. Sulfur sprays reduced HRM populations by up to 98% with the greatest effects seen in plants receiving dual applications, one during the vegetative period in July and the second at the initiation of flowering in August. Yields of plants treated with sulfur increased by up to 33%, and there was a further increase in cannabinoid production by up to 45% relative to untreated plants. Hot water immersion treatments with and without surfactant solution reduced HRM on infested hemp cuttings, and no phytotoxicity was observed. This study provides novel approaches to mitigating HRM at multiple stages in hemp production.


Chiral calcium-BINOL phosphate catalyzed diastereo- and enantioselective synthesis of syn-1,2-disubstituted 1,2-diamines: scope and mechanistic studies.
A highly enantioselective, chiral, Lewis acid calcium-bis(phosphate) complex, Ca[3 a]n, which catalyzes the electrophilic amination of enamides with azodicarboxylate derivatives 2 to provide versatile chiral 1,2-hydrazinoimines 4 is disclosed. The reaction gives an easy entry to optically active syn-1,2-disubstituted 1,2-diamines 6 in high yields with excellent enantioselectivities, after a one-pot reduction of the intermediate 1,2-hydrazinoimines 4. The geometry and nature of the N-substituent of the enamide affect dramatically both the reactivity and the enantioselectivity. Although the calcium-bis(phosphate) complex was a uniquely effective catalyst, the exact nature of the active catalytic species remains unclear. NMR spectroscopy and MS analysis of the various calcium complexes Ca[3]n reveals that the catalysts exist in various oligomer forms. The present mechanistic study, which includes nonlinear effects and kinetic measurements, constitutes a first step in understanding these calcium-bis(phosphate) complex catalysts. DFT calculations were carried out to explore the mechanism and the origin of the enantioselectivity with the Ca[3]n catalysts.


Breakfast Consumption in French Children, Adolescents, and Adults: A Nationally Representative Cross-Sectional Survey Examined in the Context of the International Breakfast Research Initiative.
This study examines the consumption of breakfast on the basis of a 7-day dietary record (Comportements et Consommations Alimentaires en France 2012⁻2013) in a representative sample of French children (n = 426), adolescents (n = 250), and adults (n = 1045). A large majority of the participants were regular consumers of breakfast (5⁻7 times per week). Breakfast accounted for 17.6% of total daily energy (339.4 kcal). Breakfast was rich in carbohydrates (24% of total daily intake) and simple sugars (31% of total daily intake). Relative to its contribution in daily energy intake, breakfast contributed higher proportions in the daily intake of many vitamins (B, C), and minerals (calcium, iron, iodine, manganese, phosphorus, potassium, magnesium). The main foods/beverages contributing to breakfast changed with age, with increasing contributions of non-wholegrain "bread and toasts" and "fruits", and a decreasing contribution of milk. Better quality of the diet, as measured by tertiles of the Nutrient Rich Food Index 9.3, was associated with higher intakes of cereal products (bread and breakfast cereals, particularly wholegrain), dairy (milk, fresh dairy), and fruit at breakfast. In conclusion, breakfast is regularly consumed in France and contributes significantly to diet quality but could be improved in terms of content in fiber and protein.


Immunosuppressive effect of radiotherapy on patients with lung cancer.
The immunoglobulins A, E, G and M of 25 patients with lung cancer were determined (by radial immunodiffusion) before, during and after radiotherapy. No significant change in any immunoglobulin were noticed overall. In the group with a poor prognosis (survival less than 12 months; 15 patients), there was a significant decrease of IgA and IgM one month after the irradiation. In the group of patients with pulmonary infection (14 patients), the level of IgA, IgG and IgM were lower than in the group without infection throughout the examination period. Cellular immunity measured by the PPD skin test, showed no significant differences between the groups by survival.


Epidemiological and virological characterization of a large community-wide outbreak of hepatitis A in southern Italy.
A large outbreak of hepatitis A virus (HAV) infection occurred in 2004 in Campania, a region of southern Italy, with 882 cases reported between 1 January and 1 August. The local public health authorities and the Italian National Institute of Health carried out investigations in order to characterize the agent, identify the source of infection and the route of transmission, and implement appropriate control measures. A web-based reporting system enhanced the flow of information between public health authorities, providing real-time epidemic curves and frequency distributions. The same 1B HAV genotype was found in 90% of sera from a subset of patients with acute disease, suggesting a local common source. A case-control study in the municipality with the highest attack rate showed that raw seafood consumption, in particular if illegally sold in water, was strongly associated with HAV illness. Samples of seafood systematically collected from retailers were found contaminated by HAV.


Room-Temperature and Tunable Tunneling Magnetoresistance in Fe3GaTe2-Based 2D van der Waals Heterojunctions.
Magnetic tunnel junctions (MTJs) based on van der Waals (vdW) heterostructures with sharp and clean interfaces on the atomic scale are essential for the application of next-generation spintronics. However, the lack of room-temperature intrinsic ferromagnetic crystals with perpendicular magnetic anisotropy has greatly hindered the development of vertical MTJs. The discovery of room-temperature intrinsic ferromagnetic two-dimensional (2D) crystal Fe3GaTe2 has solved the problem and greatly facilitated the realization of practical spintronic devices. Here, we demonstrate a room-temperature MTJ based on a Fe3GaTe2/WS2/Fe3GaTe2 heterostructure for the first time. The tunneling magnetoresistance (TMR) ratio is up to 213% with a high spin polarization of 72% at 10 K, the highest ever reported in Fe3GaTe2-based MTJs up to now. A tunneling spin-valve signal robustly persists at room temperature (300 K) with a bias current down to 10 nA. Moreover, the spin polarization can be modulated by bias current and the TMR shows a sign reversal at a large bias current. Our work sheds light on the potential application of low-energy consumption in all-2D vdW spintronics and offers alternative routes for the electronic control of spintronic devices.


Conjugate lateral eye movements as an index of hemispheric activation.
Right handers moved their eyes leftward when solving spatial problems and rightward for verbal problems when the questioner sat behind them. When facing the questioner, the same subjects moved their eyes predominantly in only one direction, either right or left, regardless of problem type. The results indicate that the cerebral hemispheres, though specialized for problem type, are also preferentially activated within the same individuals.


Basic reference aids for small medical libraries.
Selected primarily for the small medical library, this list is compiled to serve as a practical guide for the librarian in developing and utilizing an effective reference collection. Arrangement is by broad subject groups; titles chosen are chiefly in English with geographic coverage limited to the United States and Canada. Texts in subject fields have been omitted since these are adequately covered in several comprehensive guides to the literature.


Should we use antidepressant medications for children and adolescents with depressive disorders?
Most of the randomized controlled trials (RCTs) on the acute treatment of children and adolescents with major depressive disorder (MDD) have shown about 50 percent response to both tricyclic antidepressants (TCAs) and placebo. In contrast, a recent RCT found fluoxetine superior to placebo for the treatment of depressed youth. Cognitive-behavioral psychotherapy has also been found efficacious for the treatment of youth with depression. Therefore, the use of medications in particular TCAs, as the first line of treatment for youth with mild to moderate MDD has been questioned. However, some subgroups of patients, especially those who are unable or unwilling to undergo psychotherapy and those with psychosis, bipolar depression, severe depressions, or recurrent episodes, may benefit from initial treatment with antidepressants. Further research on the continuation and maintenance treatment phases of depression as well as treatment for dysthymia, treatment-resistant depression, and other subtypes of depressions is warranted.


[Advances in the investigation of biological effect and surface modification of dendrimers as drug (gene) delivery systems].
Dendrimers are highly branched macromolecules that have attractive nano-sized architectures. It seems that they can enter various cells easily because of their unique nanostructures and chemical properties, which make them to be one of important candidates of non-virus carriers for drug delivery or gene therapy. However, the understanding of cytotoxicity and related mechanisms of dendrimers are still limited. In recent years there has been rapid increases of researches regarding the biological effects of dendrimers, including the interactions of dendrimers to cells, transport mechanisms, intracellular distribution and biodistribution in vivo, as well as improvement of biocompatibility of dendrimers by surface engineering. In this paper, recent advances in the investigations of biological effect and surface modification for the dendrimers as drug or gene delivery systems were reviewed.


A fast track clinic improves diagnosis and treatment times for those investigated for lung cancer in Northland District Health Board.
In 2009, a Respiratory Fast Track Clinic (RFTC) was introduced successfully by Southern District Health Board. Advancing on this model by incorporating further biopsy methods, we aimed to streamline our investigative cancer pathway. The RFTC introduction was bi-phasic with staggered introduction of computed tomography (CT), and then biopsy, to the first service appointment (FSA). Patients with suspected lung cancer were identified for a six-month period preceding the RFTC. The time for the diagnostic pathway was then contrasted to the two RTFC introductory phases. In total, 212 patients were investigated for suspected lung cancer. Endobronchial ultrasound (EBUS) was the most utilised biopsy method. Time from GP referral to FSA improved significantly (p=0.005). Similarly, time from FSA to diagnosis and treatment improved, median times reducing from 15 to 0 (p=<0.001) and from 37 to 24 days (p=0.004) respectively. The RTFC significantly shortened time to diagnosis and treatment. To the best of our knowledge, this is the first study demonstrating a reduction in time to treatment for suspected lung cancer patients in an Australasian fast track clinic. EBUS, when utilised as the initial investigation, results in faster treatment and, may improve survival if incorporated into the RFTC model.


[Epidemiological trends in new diagnoses of HIV-1 infection in children].
In the last few years, the immigrant population in Spain, as well as the number of HIV-infected patients from countries where the prevalence of HIV-1 infection is higher, have continued to increase. No data are available on the impact of immigration on new cases of HIV-1 diagnosed in children. The objective of this study was to assess the clinical characteristics and determine the epidemiological trend of new diagnoses of pediatric HIV infection in Madrid in the last 8 years. We performed a retrospective study through review of the medical records of children in whom a new diagnosis HIV-1 infection was made in nine hospitals in the Autonomous Community of Madrid from 1997 to 2004. Two periods were compared: before December 2000 (period A) and after December 2000 (period B). Children born outside Spain or those whose parents had arrived in Spain in the previous 10 years were considered immigrants. During the period analyzed, 97 children with HIV infection were identified and transmission was vertical in 93. Overall, 33 (34%) were immigrants (51% from Latin America, 27% from sub-Saharan Africa, 15% from the Maghreb, and 6% from Eastern Europe). The percentage of immigrant children increased from 26% (19/72) in period A to 56% (14/25) in period B (p: 0.013). The mean age at diagnosis was 3.9 +/- 0.8 years in the immigrant group and 3.7 +/- 0.5 in the group of Spanish children (p > 0.05). No differences were found in the type of transmission, CDC-clinical class, viral load or CD4 cells between Spanish and immigrant children. The proportion of immigrant children with HIV-1 infection is increasing in Madrid. In our experience, we found no significant differences in clinical or immunological category between immigrant and Spanish children with regard to diagnosis of HIV infection.


Topographic enhancement of vertical turbulent mixing in the Southern Ocean.
It is an open question whether turbulent mixing across density surfaces is sufficiently large to play a dominant role in closing the deep branch of the ocean meridional overturning circulation. The diapycnal and isopycnal mixing experiment in the Southern Ocean found the turbulent diffusivity inferred from the vertical spreading of a tracer to be an order of magnitude larger than that inferred from the microstructure profiles at the mean tracer depth of 1,500 m in the Drake Passage. Using a high-resolution ocean model, it is shown that the fast vertical spreading of tracer occurs when it comes in contact with mixing hotspots over rough topography. The sparsity of such hotspots is made up for by enhanced tracer residence time in their vicinity due to diffusion toward weak bottom flows. The increased tracer residence time may explain the large vertical fluxes of heat and salt required to close the abyssal circulation.


Clinical diagnosis of vestibular disorders. A system approach to dizziness.
During recent decades, vestibular research has emphasized that it is important to consider vestibular reflexes a part of the integrated balance system function. Vestibular diagnosis must be based on a system approach to vestibular dysfunction. The development of new balance system examination methods is based on computerization of the analysis of transfer functions. Using these methods, system dysfunction is more easily understood and a new universe of vestibular diagnosis might develop in the years to come.


Brain-derived neurotrophic factor modulates the development of the dopaminergic network in the rodent retina.
Dopaminergic cells in the retina express the receptor for brain-derived neurotrophic factor (BDNF) (). To investigate whether BDNF can influence the development of the retinal dopaminergic pathway, we performed intraocular injections of BDNF during the second or third postnatal week and visualized the dopaminergic system with tyrosine hydroxylase (TH) immunohistochemistry. Both regimens of BDNF treatment caused an increase in TH immunoreactivity in stratum 1 and stratum 3 of the inner plexiform layer (IPL). D2 dopamine receptor immunoreactivity, a presynaptic marker of dopaminergic cells (), was also increased in stratum 1 and stratum 3 of the inner plexiform layer. These data suggest that BDNF causes sprouting of dopaminergic fibers in the inner plexiform layer. Other neurochemical systems, for example, the cholinergic amacrine cells, remained unaffected. Similar effects were observed after injections of neurotrophin-3 and neurotrophin-4, but not nerve growth factor. Analysis of whole-mounted TH-immunolabeled retinae revealed hypertrophy of dopaminergic cells (+41% in soma areas; p < 0.01) and an increase of labeled dopaminergic varicosities in stratum 1 of the IPL (+51%; p < 0.01) after BDNF treatment. The opposite was observed in mice homozygous for a null mutation of the bdnf gene: dopaminergic cells were atrophic (-22.5% in soma areas; p < 0.05), and the density of TH-positive varicosities in stratum 1 was reduced (57%; p < 0.01). We conclude that BDNF controls the development of the retinal dopaminergic network and may be particularly important in determining the density of dopaminergic innervation in the retina.


Derivation, culture and retinal pigment epithelial differentiation of human embryonic stem cells using human fibroblast feeder cells.
Retinal pigment epithelium cells derived from human embryonic stem cells (ESCs) could be useful for restoring retinal function in age-related macular degeneration. However the use of non-human feeder cells to support the growth of ESCs for clinical applications raises the concern of possible contamination because of direct contact between animal and human cells. In this study, we produced human ESCs using human fibroblast feeder layers isolated from foreskin and abdominal tissues. Using this system, human ESCs differentiated into retinal pigment epithelium cells in differentiation medium. Seven human ESC lines were established from 18 blastocysts. These human ESCs showed normal morphology, expressed all expected cell surface markers, had the ability to form embryoid bodies upon culture in vitro and teratomas after injection into SCID mice, and differentiated further into derivatives of all three germ layers. Under conditions of committed differentiation, these human ESCs could differentiate into retinal pigment epithelium cells after 2 months in culture. The results of this study demonstrated that human foreskin/abdominal fibroblasts have the potential to support the derivation and long-term culture of human ESCs, which can then be used to generate retinal pigment epithelium cells with characteristic morphology and molecular markers. This technique avoids the concerns of contamination from animal feeder layers during human ESC derivation, culture and differentiation, and will thus facilitate the development of retinal pigment epithelium cell transplantation therapy.


Efficient retroviral-mediated gene transfer to human cord blood stem cells with in vivo repopulating potential.
Recent studies have shown efficient gene transfer to primitive progenitors in human cord blood (CB) when the cells are incubated in retrovirus-containing supernatants on fibronectin-coated dishes. We have now used this approach to achieve efficient gene transfer to human CB cells with the capacity to regenerate lymphoid and myeloid progeny in nonobese diabetic (NOD)/severe combined immunodeficiency (SCID) mice. CD34(+) cell-enriched populations were first cultured for 3 days in serum-free medium containing interleukin-3 (IL-3), IL-6, granulocyte colony-stimulating factor, Flt3-ligand, and Steel factor followed by two 24-hour incubations with a MSCV-NEO virus-containing medium obtained under either serum-free or serum-replete conditions. The presence of serum during the latter 2 days made no consistent difference to the total number of cells, colony-forming cells (CFC), or long-term culture-initiating cells (LTC-IC) recovered at the end of the 5-day culture period, and the cells infected under either condition regenerated similar numbers of human CD34(+) (myeloid) CFC and human CD19(+) (B lymphoid) cells for up to 20 weeks in NOD/SCID recipients. However, the presence of serum increased the viral titer in the producer cell-conditioned medium and this was correlated with a twofold to threefold higher efficiency of gene transfer to all progenitor types. With the higher titer viral supernatant, 17% +/- 3% and 17% +/- 8%, G418-resistant in vivo repopulating cells and LTC-IC were obtained. As expected, the proportion of NEO + repopulating cells determined by polymerase chain reaction analysis of in vivo generated CFC was even higher (32% +/- 10%). There was no correlation between the frequency of gene transfer to LTC-IC and colony-forming unit-granulocyte-macrophage (CFU-GM), or to NOD/SCID repopulating cells and CFU-GM (r2 = 0.16 and 0.17, respectively), whereas values for LTC-IC and NOD/SCID repopulating cells were highly and significantly correlated (r2 = 0.85). These findings provide further evidence of a close relationship between human LTC-IC and NOD/SCID repopulating cells (assessed using a >/= 6-week CFC output endpoint) and indicate the predictive value of gene transfer measurements to such LTC-IC for the design of clinical gene therapy protocols.


Associations of non-alcoholic fatty liver disease and cirrhosis with liver cancer in European and East Asian populations: A Mendelian randomization study.
The positive relationships of non-alcoholic fatty liver disease (NAFLD) and cirrhosis with liver cancer were shown in previous observational studies, while further Mendelian randomization (MR) investigations are needed to confirm the possible causal associations. This study aimed to explore whether NAFLD and cirrhosis were causally related to liver cancer using MR in European and East Asian populations. For European populations, NAFLD data were obtained from a genome-wide meta-analysis (8434 patients and 770 180 controls). The data on chronic elevation of alanine aminotransferase (cALT), a proxy of NAFLD, were derived from Million Veteran Program (68 725 patients and 95 472 controls). Cirrhosis data were collected from two sources: a genome-wide association study of five cohorts (4829 patients and 72 705 controls) and FinnGen (1931 patients and 216 861 controls). Liver cancer data were collected from FinnGen (304 patients and 174 006 controls). For East Asian populations, the data on cirrhosis (2184 patients and 210 269 controls) and hepatocellular carcinoma (1866 patients and 195 745 controls) were obtained from Biobank Japan. Three, 41, seven, six, and three single-nucleotide polymorphisms were used for NAFLD (European), cALT (European), cirrhosis (European-five cohorts), cirrhosis (European-FinnGen), and cirrhosis (East Asian), respectively. We used inverse-variance weighted as the primary method to calculate the odds ratio (OR) and 95% confidence interval (CI). Among European populations, genetically-predicted NAFLD, cALT, cirrhosis (five cohorts), and cirrhosis (FinnGen) were positively associated with liver cancer, with ORs (95% CIs) of 6.62 (3.81-11.50) (p < .001), 2.59 (1.70-3.94) (p < .001), 3.38 (2.41-4.75) (p < .001), and 2.62 (1.20-5.72) (p = .015). Among East Asian populations, there was also a positive association between genetically-predicted cirrhosis and hepatocellular carcinoma (OR = 2.12; 95% CI = 1.78-2.52; p < .001). This study utilized MR to complementarily confirm the positive connections of NAFLD and cirrhosis with liver cancer, as identified in earlier observational research. Subsequent MR investigations involving more liver cancer cases are needed.


Colonization of Mansonia dives Schiner in a field insectary.
Successful colonization of Mansonia dives, the principal vector of subperiodic Brugia malayi was established in a field insectary. Mean egg clusters laid on Eichhornia crassipes, Pistia stratiotes, Homalomena cordata and polystyrofoam strips were 12.0, 10.4, 9.5 and 13.7 respectively. However, the mean number of first instar larvae hatched from each egg cluster laid by females on the three plant substrates (range 51.1 to 58.6) was higher than that laid on the polystyrofoam strips (41.8). There were no significant differences in the success pupation and adult emergence rates among the three host plants used as attachment substrates. Adult emergence occurred at a mean of 10.8 days. The first adult emergence was observed at the 25th day after hatching and continued till the 50th day. The 50% mortality rates for the adults were estimated as 8 days for the males and 14 days for the females. The mean gonotrophic cycle ranged from 3.8 to 4.3 days with a mean of 4.04 days. 63.6% of Ma. dives females oviposited in a medium of rat dung and water. The mean incubation period of eggs ranged from 5.2 to 6.5 days with a mean of 5.7 days. The biology of Ma. dives and Ma. bonneae is briefly compared.


A model of myosin V processivity.
Cytoplasmic transport is mediated by a group of molecular motors that typically work in isolation, under conditions where they must move their cargos long distances without dissociating from their tracks. This processive behavior requires specific adaptations of motor enzymology to meet these unique physiologic demands. One of these involves the ability of the two heads of a processive motor to communicate their structural states to each other. In this study, we examine a processive motor from the myosin superfamily myosin V. We have measured the kinetics of nucleotide release, of phosphate release, and of the weak-to-strong transition, as this motor interacts with actin, and we have used these studies to develop a model of how myosin V functions as a transport motor. Surprisingly, both heads release phosphate rapidly upon the initial encounter with an actin filament, suggesting that there is little or no intramolecular strain associated with this step. However, ADP release can be affected by both forward and rearward strain, and under steady-state conditions it is essentially prevented in the lead head until the rear head detaches. Many of these features are remarkably like those underlying the processive movement of kinesin on microtubules, supporting our hypothesis that different molecular motors satisfy the requirement for processive movement in similar ways, regardless of their particular family of origin.


Critical Impact of Peptidoglycan Precursor Amidation on the Activity of l,d-Transpeptidases from Enterococcus faecium and Mycobacterium tuberculosis.
The bacterial cell wall peptidoglycan contains unusual l- and d-amino acids assembled as branched peptides. Insight into the biosynthesis of the polymer has been hampered by limited access to substrates and to suitable polymerization assays. Here we report the full synthesis of the peptide stem of peptidoglycan precursors from two pathogenic bacteria, Enterococcus faecium and Mycobacterium tuberculosis, and the development of a sensitive post-derivatization assay for their cross-linking by l,d-transpeptidases. Access to series of stem peptides showed that amidation of free carboxyl groups is essential for optimal enzyme activity, in particular the amidation of diaminopimelate (DAP) residues for the cross-linking activity of the l,d-transpeptidase LdtMt2 from M. tuberculosis. Accordingly, construction of a conditional mutant established the essential role of AsnB indicating that this DAP amidotransferase is an attractive target for the development of anti-mycobacterial drugs.


Nucleic acid carriers based on precise polymer conjugates.
Polymer polydispersity, random conjugation of functional groups, and poorly understood structure-activity relationships have constantly hampered progress in the development of nucleic acid carriers. This review focuses on the synthetic concepts for the generation of precise polymers, site-specific conjugation strategies, and multifunctional conjugates for nucleic acid transport. Dendrimers, defined peptide carriers, sequence-defined polyamidoamines assembled by solid-phase supported synthesis, and precise lipopeptides or lipopolymers have been characterized for pDNA and siRNA delivery. Conjugation techniques such as click chemistries and peptide ligation are available for conjugating polymers with functional transport elements such as targeting or shielding domains and for direct covalent modification of therapeutic nucleic acids in a site-specific mode.


Unconjugated bile acids in rat brain: Analytical method based on LC/ESI-MS/MS with chemical derivatization and estimation of their origin by comparison to serum levels.
Although some studies have revealed the implication of bile acids (BAs) and neurological diseases, the levels and origin of the BAs in the brain are not fully understood. In this study, we first developed and validated a sensitive and specific method for the determination of three unconjugated BAs [cholic acid (CA), chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA)] in the rat brain by liquid chromatography/electrospray ionization-tandem mass spectrometry combined with chemical derivatization. The measured brain concentrations (mean±standard deviation, n=10) of normal rats were 58.7±48.8, 14.2±11.7 and 13.2±8.7ng/g tissue for CA, CDCA and DCA, respectively. For their origin, we developed the hypothesis that they might be mostly derived from the periphery. To test this hypothesis, the brain BA levels were compared with the serum levels. The brain levels had high correlations with the serum levels, and were always lower than the serum levels for the three unconjugated BAs. Furthermore, the higher brain-to-serum concentration ratios were found for the BAs with higher logD values (higher lipophilicity). Moreover, the brains of the rats intraperitoneally administered with deuterium-labeled CA and CDCA were also analyzed; the deuterium-labeled BAs were detected in the brain of the rats administered with these compounds. Based on all the results, we concluded that the BAs found in the brain are mostly derived from the periphery and the major mechanism for the transportation of the unconjugated BAs to the brain is by passive diffusion.


Beta2-microglobulin, carcinoembryonic antigen and prostatic acid phosphatase in split ejaculates and urine voided before and after massage of the prostate.
Analyses of split ejaculates and urine voided before and after prostatic massage have been used to evaluate the origin of beta2-microglobulin (b2m) and carcinoembryonic antigen (CEA) in human semen. CEA and b2m were present in rather high concentrations in all the fractions of the split ejaculates. The urine voided after massage of the prostate also contained increased levels of CEA and beta2-microglobulin. Split ejaculates, selected from the electrophoretic pattern obtained for each fraction, revealed that b2m in seminal plasma originates from the prostate and seminal vesicles in equal amounts. Besides the "free" b2m in seminal plasma, human semen contains a sperm-bound b2m fraction. Carcinoembryonic antigen was found in the highest concentrations in the second fraction of split ejaculates indicating that it originates mainly from the prostate.


Oral Glutamine May Have No Clinical Benefits to Prevent Radiation-Induced Oral Mucositis in Adult Patients With Head and Neck Cancer: A Meta-Analysis of Randomized Controlled Trials.
Objectives: The role of oral glutamine for the management of oral mucositis (OM) has not yet been confirmed. The objective of the present study is to further investigate whether oral glutamine is effective in preventing and treating OM among patients with head and neck cancer (HNC) receiving radiotherapy alone or concurrent with chemotherapy. Methods: A systematic search was performed in PubMed, EMBASE, EBSCO, and Cochrane Central Register of Controlled Trials (CENTRAL) to capture all potential citations from the inception to June 2019. Then data extraction and assessment of risk of bias were carried out after selecting the eligible citations. RevMan 5.3 software was used to perform all statistical analyses. Results: Six randomized controlled trials (RCTs) including 441 patients were included in the final analysis. The meta-analysis showed that oral glutamine couldn't significantly decrease the incidence of OM (risk ratio [RR] = 0.98, 95% confidence interval [CI] = 0.94-1.02) and alleviate the development of moderate or severe grade of OM (Moderate-to-severe OM: RR = 0.81, 95% CI = 0.59-1.12; Severe OM: RR = 0.45, 95% CI = 0.13-1.52). But oral glutamine may have the potential to reduce the opioid use (RR = 0.84, 95% CI = 0.71-0.99). The role of oral glutamine in delaying the onset of OM remains uncertain due to conflicting results between quantitative (mean difference [MD] = 4.11 days, 95% CI = 3.49-4.73) and qualitative results. Conclusions: Oral glutamine may have no clinical benefits to prevent or reduce the incidence and severity of radiation-induced OM in patients with HNC receiving radiotherapy alone or concurrent with chemotherapy. It is also uncertain whether oral glutamine can delay the onset of OM. But it may have the potential to relieve the degree of oral pain. Nevertheless, we must cautiously interpret the results because the observed effect size for delay in mucositis start or reduction in opioid use is marginal. Moreover, further RCTs with more rigorous methodology and large-scale are required to enhance the quality of evidence.


On the concept of hemilability: insights into a donor-functionalized iridium(I) NHC motif and its impact on reactivity.
Novel iridium(I) complexes bearing N-donor-functionalized N-heterocyclic carbene ligands were synthesized. Although hemilabile coordination of the attached donor is considered beneficial in catalysis, no detailed study of this phenomenon in these systems is available to date. The present report provides insight into the hemilabile bonding properties of a N,N'-bis(pyridin-2-yl)-imidazolylidene (NCN) ligand motif on iridium(I). In most cases, the presented compounds exhibit rare fluxional hemilabile coordination of the N donor, and remarkable performance in catalytic transfer hydrogenation is observed. Further, extensive reactivity studies often led to unexpected products.


Can social and agonistic interactions be used to detect anxiolytic activity of drugs?
Majority of adult male albino random-bred mice housed singly or in small groups show agonistic behavior on interaction with a strange male mouse: some of them are predominantly aggressive ('aggressive' mice) while others show defenses or escapes even though their partners are not aggressive ('timid' mice). The remaining males not exhibiting agonistic behavior ('sociable' mice) show more social investigation then aggressive or timid mice and more locomotion then timid mice. Active defensive-escape behavior ('timidity') and inhibition of social investigation and of locomotion is much stronger in an unfamiliar cage with a strange male than in a home cage or on interaction with a female. Effects of 50 drugs on behavior of aggressive and timid male mice on agonistic interactions with non-aggressive male mice in neutral cages were tested. Most of the drugs possessing anxiolytic activity in man reduced active escapes or defenses at doses lower than those inhibiting attacks or locomotion and increased social investigation while most drugs without anxiolytic activity did not show these effects. Some anxiolytic drugs reduced tail-rattling (an ambivalent activity presumably reflecting both attack and escape tendency) at doses lower than those reducing attacks and increased locomotion. Only some benzodiazepines (nitrazepam, oxazepam and diazepam) produced the whole spectrum of these effects indicating a reduced defensive-escape tendency. The present results suggest that a selective inhibition of defensive-escape tendency on agonistic interactions can be a good predictor of anxiolytic activity of drugs. Profiles of effects of seven benzodiazepines in the present model of agonistic interaction to some extent differed: triazolam, clonazepam and flunitrazepam were more sedating (reduced timidity only at doses inhibiting locomotion) while nitrazepam, oxazepam, diazepam and chlordiazepoxide were less sedating (reduced timidity at non-sedative doses, stimulated social investigation and locomotion). Only drugs stimulating GABA-receptor complex (benzodiazepines, barbiturates and GABAergic drugs) inhibited active escapes and defenses at doses lower than those reducing attacks. This suggests that the GABA-receptor complex is involved in regulation of defensive-escape tendency in intraspecies conflict.


The Ionic Products from Mineral Trioxide Aggregate-induced Odontogenic Differentiation of Dental Pulp Cells via Activation of the Wnt/β-catenin Signaling Pathway.
Mineral trioxide aggregate (MTA) has been successfully used in clinical applications in endodontics. However, little is known about the involvement of Wnt/β-catenin signaling in human dental pulp cells (hDPC) differentiation with the interaction of MTA in hard tissue regeneration, especially in odontogenesis. Therefore, the aim of this study was to explore odontogenic/osteogenic gene expression and the protein secretion of hDPCs cultured with consecutive concentrations of MTA extracts and carefully examine the particular molecular mechanism that occurs during this process. MTA extracts were prepared by immersing MTA powders into Dulbecco modified Eagle medium at a concentration of 200 mg/mL. hDPCs were cultured with various concentrations of MTA extracts, and the resulting changes in the cells, such as proliferation and odontogenic differentiation, were measured. The results indicate that hDPC proliferation increases remarkably in a time-dependent manner in most treatment groups, except the highest concentration group (200 mg/mL). The Wnt/β-catenin signaling pathway-related genes and proteins are significantly raised when hDPCs are cultured in a wide concentration range of MTA extracts compared with a control, except for the highest concentration group (100 mg/mL), on days 3 and 7 (P < .05). These variations indicate that Wnt/β-catenin signaling is involved in MTA extract-induced odontogenic differentiation of hDPCs.


Fluorescence energy transfer monitored competitive equilibria of nucleic acids: applications in thermodynamics and screening.
Precise thermodynamic characterization of nucleic acid complex stability is required to understand a variety of biologically significant events as well as to exploit the specific recognition capabilities of nucleic acids in biotechnology, diagnostics, and therapeutics. The development of a database of nucleic acid thermodynamics with sufficient precision to foster further developments in these areas requires new and improved measurement techniques. The combination of a competitive equilibrium titration with fluorescence energy transfer based detection provides a method for precise measurement of differences in free energy values for nucleic acid duplexes that far exceeds in precision those accessible via conventional methods. The method can be applied to detect and to characterize any deviation in a nucleic acid that alters duplex stability. Such deviations include, but are not limited to, mismatches; single nucleotide polymorphisms (SNP); chemically modified nucleotide bases, sugars or phosphates; and conformational anomalies or folding motifs, such as, loops or hairpins.


Anti-SARS CoV-2 IgG in COVID-19 Patients with Hematological Diseases: A Single-center, Retrospective Study in Japan.
Objective Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread globally. Although the relationship between anti-SARS-CoV-2 immunoglobulin G (IgG) antibodies and COVID-19 severity has been reported, information is lacking regarding the seropositivity of patients with particular types of diseases, including hematological diseases. Methods In this single-center, retrospective study, we compared SARS-CoV-2 IgG positivity between patients with hematological diseases and those with non-hematological diseases. Results In total, 77 adult COVID-19 patients were enrolled. Of these, 30 had hematological disorders, and 47 had non-hematological disorders. The IgG antibody against the receptor-binding domain of the spike protein was detected less frequently in patients with hematological diseases (60.0%) than in those with non-hematological diseases (91.5%; p=0.029). Rituximab use was significantly associated with seronegativity (p=0.010). Conclusion Patients with hematological diseases are less likely to develop anti-SARS-CoV-2 antibodies than those with non-hematological diseases, which may explain the poor outcomes of COVID-19 patients in this high-risk group.


From localization to anomalous diffusion in the dynamics of coupled kicked rotors.
We study the effect of many-body quantum interference on the dynamics of coupled periodically kicked systems whose classical dynamics is chaotic and shows an unbounded energy increase. We specifically focus on an N-coupled kicked rotors model: We find that the interplay of quantumness and interactions dramatically modifies the system dynamics, inducing a transition between energy saturation and unbounded energy increase. We discuss this phenomenon both numerically and analytically through a mapping onto an N-dimensional Anderson model. The thermodynamic limit N→∞, in particular, always shows unbounded energy growth. This dynamical delocalization is genuinely quantum and very different from the classical one: Using a mean-field approximation, we see that the system self-organizes so that the energy per site increases in time as a power law with exponent smaller than 1. This wealth of phenomena is a genuine effect of quantum interference: The classical system for N≥2 always behaves ergodically with an energy per site linearly increasing in time. Our results show that quantum mechanics can deeply alter the regularity or ergodicity properties of a many-body-driven system.


Cochlear Nerve Deficiency in Pediatric Unilateral Hearing Loss and Asymmetric Hearing Loss.
The rates of cochlear nerve abnormalities and cochlear malformations in pediatric unilateral hearing loss (UHL) are conflicting in the literature, with important implications on management. The aim of this study was to investigate the incidence of cochlear nerve deficiency (CND) in pediatric subjects with UHL or asymmetric hearing loss (AHL). A retrospective chart review of pediatric subjects <18 years of age evaluated for UHL or AHL with fine-cut heavily T2-weighted magnetic resonance imaging (MRI) between January 2014 and October 2019 (n = 291) at a tertiary referral center was conducted. MRI brain and computed tomography temporal bone were reviewed for the presence of inner ear malformations and/or CND. Status of the ipsilateral cochlear nerve and inner ear was evaluated. Pure tone average (PTA) at 500, 1,000 and 2,000 Hz was assessed. 204 subjects with UHL and 87 subjects with AHL were included. CND (aplasia or hypoplasia) was demonstrated in 61 pediatric subjects with UHL (29.9%) and 10 with AHL (11.5%). Ipsilateral cochlear malformations were noted in 25 subjects with UHL (12.3%) and 11 with AHL (12.6%), and ipsilateral vestibular malformations in 23 (11.3%) and 12 (13.8%) ears, respectively. Median PTA was statistically significantly higher in ears with CND (98.33) than ears with normal nerves (90.84). Imaging demonstrated a high incidence of inner ear malformations, particularly CND, in pediatric subjects with UHL. Auditory findings indicated CND cannot be ruled out by thresholds alone as some CND ears did demonstrate measurable hearing. Radiologic evaluation by MRI should be performed in all patients within this population to guide counseling and management of hearing loss based on etiology, with implications on candidacy for cochlear implantation.


Chloracne caused by ingestion of olive oil contaminated with PCDDs and PCDFs.
1. All members of a Spanish family (father, mother and six children) developed chloracne. 2. The causative agent was found to be the family's stock of olive oil, which had become contaminated with polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), pentachlorophenol, and hexachlorobenzene. 3. The more highly chlorinated PCDDs, in particular octachlorodibenzo-p-dioxin, were the predominant congeners in the oil. 4. Three members of the family exhibited either an overt or a sub-clinical disturbance of kidney function. The father also had a chronic respiratory problem. These changes could not be unequivocally attributed to the PCDDs. 5. Experimental toxicity of the oil was limited to the development of an hepatic porphyria in mice. 6. A serum sample, taken 5 years after consumption of the oil ceased, contained high levels of the PCDDs and PCDFs. Extrapolation back to ingested dose was used to validate dosage estimates. 7. The use of toxicity equivalence factors (TEFs) provided estimates of cumulative dosage to produce chloracne as 0.13-0.31 micrograms 2378-TCDD kg-1 (using EPA TEFs) or 6.7-16 micrograms 2378-TCDD kg-1 (using Nordic/NATO TEFs). 8. This is the first incident in which human toxicity is related primarily to ingestion of PCDDs and for which estimates of dosage can be made.


ICT in health care: sociotechnical approaches.
The importance of the social sciences for medical informatics is increasingly recognized. As ICT requires inter-action with people and thereby inevitably affects them, understanding ICT requires a focus on the interrelation between technology and its social environment. Sociotechnical approaches increase our understanding of how ICT applications are developed, introduced and become a part of social practices. Socio-technical approaches share several starting points: 1) they see health care work as a social, 'real life' phenomenon, which may seem 'messy' at first, but which is guided by a practical rationality that can only be overlooked at a high price (i.e. failed systems). 2) They see technological innovation as a social process, in which organizations are deeply affected. 3) Through in-depth, formative evaluation, they can help improve system design and implementation.


Amyloid-β disrupts ongoing spontaneous activity in sensory cortex.
The effect of Alzheimer's disease pathology on activity of individual neocortical neurons in the intact neural network remains obscure. Ongoing spontaneous activity, which constitutes most of neocortical activity, is the background template on which further evoked-activity is superimposed. We compared in vivo intracellular recordings and local field potentials (LFP) of ongoing activity in the barrel cortex of APP/PS1 transgenic mice and age-matched littermate CONTROLS, following significant amyloid-β (Aβ) accumulation and aggregation. We found that membrane potential dynamics of neurons in Aβ-burdened cortex significantly differed from those of nontransgenic durations of the depolarized state were considerably shorter, and transitions to that state frequently failed. The spiking properties of APP/PS1 neurons showed alterations from those of both firing patterns and spike shape were changed in the APP/PS1 group. At the population level, LFP recordings indicated reduced coherence within neuronal assemblies of APP/PS1 mice. In addition to the physiological effects, we show that morphology of neurites within the barrel cortex of the APP/PS1 model is altered compared to CONTROLS. These results are consistent with a process where the effect of Aβ on spontaneous activity of individual neurons amplifies into a network effect, reducing network integrity and leading to a wide cortical dysfunction.