Accident risk of foreign drivers--the case of Russian drivers in south-eastern Finland.
Foreign drivers are considered to be a greater risk than domestic drivers in most countries in the world. Few empirical findings have been reported, though. This paper contributes some evidence of the risk of foreign drivers in south-eastern Finland during 1992-1995. Most of the foreign drivers are Russian. Based on accident statistics collected by the police and origin-destination studies carried out on the Finnish-Russian border stations, accident rates were calculated for both Finnish and foreign drivers. The results show that accident rates of foreign drivers are higher than rates of domestic drivers. The winter season is especially risky for foreign drivers. It is argued that the traffic culture of different countries largely explain the differences rather than some specific, technical risk parameters. Some probable risk parameters can be identified in this study, such as a lack of knowledge concerning traffic rules, insufficient winter-time driving skills and winter-time equipment, as well as the general attitude towards traffic safety which is reflected in the driving behavior.


CUBITAL TUNNEL SYNDROME DUE TO AN INTRANEURAL GANGLION CYST OF THE ULNAR NERVE.
Cubital tunnel syndrome is the second most common neuropathy of the upper extremity. Cubital tunnel syndrome caused by intraneural ganglion cysts is rare in clinical practice. We present the case of a 71-year-old male patient with a 4-month history of cubital tunnel syndrome of the left elbow due to an intraneural ganglion cyst. After revision of the ulnar nerve and resection of the intraneural cyst nearly complete recovery was achieved within a 5 month follow-up but some sensory deficits of the fifth fingertip. We recommend preoperative ultrasound examination of the cubital tunnel even in cases with clear diagnosis. Ganglion cyst as a cause of cubital tunnel is rare but needs to be diagnosed and treated as soon as possible to prevent irreversible complications.


Intraindividual Variability across Neuropsychological Tests: Dispersion and Disengaged Lifestyle Increase Risk for Alzheimer's Disease.
Objective: Increased intraindividual variability (IIV) in function has been linked to various age-related outcomes including cognitive decline and dementia. Most studies have operationalized IIV as fluctuations across trials (e.g., response latencies) for a single task, with comparatively few studies examining variability across multiple tasks for a given individual. In the present study, we derive a multivariable operationalization of dispersion across a broad profile of neuropsychological measures and use this index along with degree of engaged lifestyle to predict risk of cognitive impairment. Participants and Methods: Participants (n = 60) were community-dwelling older adults aged 65+ years (M = 74.1, SD = 6.5) participating in a cross-sectional investigation of risk factors for amnestic mild cognitive impairment (a-MCI) and probable Alzheimer's Disease (AD). Participants were classified into three subgroups based on test performance and clinical judgement. Healthy controls (n = 30) scored better than -1 SD relative to existing norms on all classification measures, in the absence of memory complaints or functional impairments. The a-MCI group (n = 23) had self- or informant-reported memory complaints and scored 1 SD or more below the mean for at least one memory task while scoring better than 1 SD below the mean for all other cognitive domains, in the absence of functional impairments. The AD group (n = 7) scored at least 2 SD below the mean for two cognitive domains (including memory) with impairments in functioning. Measures spanned a range of cognitive domains (episodic memory, executive function, language), with the derived dispersion estimates reflecting variability across an individual's neuropsychological profile relative to the group average. Further, an Activities Lifestyle Questionnaire, indexing social, cognitive, and physical behaviors, was administered to assess the protective benefits of engaged lifestyle. Results: Multinomial logistic regression models examined the risk of being classified as a-MCI or AD as a function of increased dispersion, (dis)engaged lifestyle, and their interaction. Greater dispersion was associated with an increased likelihood of being classified with AD, with protective engaged-lifestyle benefits apparent for a-MCI individuals only. Conclusion: As a measure of IIV, dispersion across neuropsychological profiles holds promise for the detection of cognitive impairment.


Pain and quality of life in Turkish cancer patients.
This study was designed to examine the relationship between patients' pain severity and their self-reported quality of life, to evaluate factors that may affect pain and quality of life, and to assess patients' opinions and practices on the use of analgesics. The study was conducted with 260 cancer patients. Data were collected using a Quality of Life Scale and Visual Analog Scale questionnaire. It was found that mean scores of pain, all subdomains of quality of life, and overall mean scores of patients were at a moderate level, the lowest score in the subdomains of quality of life was in the psychological subdomain and the highest was in the spiritual subdomain. It was also found that as severity of pain experienced by patients increased, their general activities, mood, activeness, sleep, and nutrition were negatively affected. As severity of pain experienced by patients increased, their quality of life worsened. Patients were observed to have insufficient knowledge and a poor understanding with respect to the use of analgesics. In conclusion, it is very important for nurses to assess factors that can complicate pain management and to establish an effective pain control.


Measles virus infection of rhesus macaques affects neutrophil expression of IL-12 and IL-10.
Cytokine production by phagocytic cells is an important component of the immune response to infection with a variety of pathogens. Neutrophils are phagocytic cells capable of expressing interleukin (IL)-12 and IL-10 in response to infection with parasites, fungi, and bacteria. These cytokines are postulated to play important roles in the immune response during measles. Neutrophils isolated from naive or measles virus (MV)-infected rhesus macaques expressed IL-12 and IL-10 following in vitro stimulation with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). Stimulated neutrophils secreted proportionally more of the biologically active IL-12 heterodimer p70 and more IL-10 than similarly stimulated peripheral blood mononuclear cells (PBMCs). During MV infection, the number of IL-12 and IL-10-producing neutrophils and monocytes initially decreased. Subsequently, IL-12 levels were restored, and IL-10 expression rose above baseline in both cell types. Increased IL-10 production by neutrophils and monocytes during MV infection may play a role in measles-induced immunosuppression.


Tritrichomonas foetus and not Pentatrichomonas hominis is the etiologic agent of feline trichomonal diarrhea.
Recently, several investigators have reported large-bowel diarrhea in cats associated with intestinal trichomonad parasites. These reports have presumptively identified the flagellates as Pentatrichomonas hominis, a n organism putatively capable of infecting the intestinal tracts of a number of mammalian hosts, including cats, dogs, and man. The purpose of the present study was to determine the identity of this recently recognized flagellate by means of rRNA gene sequence analysis; restriction enzyme digest mapping; and light, transmission, and scanning electron microscopy (SEM).


The efficacy of acquired humoral and cellular immunity in the prevention and therapy of experimental fungal infections.
In the past two decades, numerous studies have documented the importance of acquired immunity for host defense against invasive fungal infections. There is widespread consensus in the field of medical mycology that cellular immunity is critical for successful host defense against fungi. However, in recent years several studies have established the potential efficacy of humoral immunity in host protection against two major fungal pathogens: Candida albicans and Cryptococcus neoformans. For C. albicans, antibodies to mannan, proteases and a heat shock proteins have been associated with protection against infection. Furthermore, anti-idiotypic antibodies to antibodies recognizing killer toxin from Pichia anomala and mimicking natural anti-killer toxin receptor antibodies can protect against C. albicans and other microorganisms. For C. neoformans, antibodies to the capsular glucuronoxylomannan have been shown to mediate protection in animal models of infection. Vaccines that induce protective antibodies have been shown to protect against experimental C. albicans and C. neoformans infection. In contrast, humoral immunity has not yet been demonstrated to mediate protection against Coccidioides immitis. For C. immitis, protection against infection is thought to rely on T cell mediated immunity, and the emphasis is on identifying the antigens that stimulate protective cellular immune responses and several candidate vaccines have been identified. These results provide encouragement for the view that acquired immune responses can be mobilized for the prevention and treatment of fungal infections.


The validity of diagnostic support of an asthma/COPD service in primary care.
To support GPs in diagnosing and monitoring their patients with asthma/chronic obstructive pulmonary disease (COPD), 'asthma/COPD services' have been developed. Within these services, pulmonologists perform structured diagnostic and therapeutic assessments based on the combination of written history data and spirometry. This study determines the validity of the diagnosis and advice when assessed using only written information. The results of the diagnostic procedures of an asthma/COPD service were compared with the results of regular office consultations by pulmonologists. From January until August 2004, two pulmonologists examined 80 randomly selected patients referred to an asthma/COPD service in Eindhoven, the Netherlands. Concordance was analysed between diagnosis and advice based on written spirometry and history data, with assessments based on live consultations with the same patients by pulmonologists. The validity of the assessed diagnosis was high (Cohen's kappa = 0.82). When the diagnosis was uncertain, the advice for medical treatment scored low in validity (Cohen's kappa = 0.39). The advice for additional diagnostic examinations had a high internal validity: in half of the patients, uncertainty in diagnosis turned into a definite diagnosis of asthma/COPD, or another cause for the complaints of the patient was revealed; in the other half, the diagnosis of asthma/COPD could be rejected. A structured asthma/COPD service offering diagnosis and diagnostic advice assessed from written spirometry and history data is a new and valid facility that can support the GP who faces the complicated diagnostic procedures in a progressive number of patients with asthma/COPD.


A retrospective study on endoscopic missing diagnosis of colorectal polyp and its related factors.
To investigate missing diagnosis of the polyp by colonoscopy, and to reveal the endoscopic, pathological features of missed polyps and related factors inducing missing diagnosis. We reviewed the data of the patients who received colonoscopy twice within 180 days. The missing rate of the colorectal polyps ware calculated and the endoscopic and pathological features of the missed polyps were summarized. Possible related factors inducing the missing diagnosis were analyzed. The missing rate of colorectal polyps in this study was 27.7%, with as high as 11.5% missing rate of advanced polyps. Most missed polyps were those of <5 mm in diameter (55.2%) or flat ones (75.9%). Most of missed polyps are located in the rectum (21.8%), sigmoid (41.4%) and transverse colon (17.2%). No significant correlation was observed between the missing rate and colonoscopic manners (p>0.05), neither between the missing rate and operators (p>0.05). But number of basal polyps was proved to be significantly correlative with number of missed polyps (r=0.694, p<0.001). Polyps of <5 mm in diameter or flat polyps are more likely to be missed in the endoscopy. Most of missed polyps are located in rectum, sigmoid and transverse colon. More basal polyps usually accompany with more polyps missed.


In vitro activities of amphotericin B and AmBisome against Aspergillus isolates recovered from Italian patients treated for haematological malignancies.
Although there is evidence that liposomal amphotericin B (AmBisome) is non-inferior to amphotericin B (AmB) in terms of in vivo efficacy, in vitro data regarding the activity of AmBisome against clinical isolates of Aspergillus are rare. In this study, the susceptibilities to AmB and AmBisome of 103 Aspergillus complex isolates (48 Aspergillus flavus, 33 Aspergillus fumigatus, 13 Aspergillus terreus and 9 Aspergillus niger) recovered from haematological patients with invasive infection were compared. Minimum inhibitory concentrations (MICs) were determined by the broth microdilution (BMD) method according to the Clinical and Laboratory Standards Institute (CLSI), whilst AmB susceptibility was also determined by Etest. Using a susceptible/resistant MIC cut-off of 1mg/L, all A. fumigatus and A. niger complexes isolates were susceptible to both AmB and AmBisome. In contrast, 38.5% and 30.8% of the A. terreus complex isolates were resistant to AmB and AmBisome, respectively, with good agreement between BMD and Etest methods. With respect to A. flavus complex isolates, 43.7% and 16.7% were resistant by the BMD method to AmBisome and AmB, respectively. For isolates with discrepant results, AmB MICs obtained by Etest were higher than those obtained for AmB by the BMD method and they were closer to those obtained for AmBisome by BMD. Aspergillus flavus AmB MICs ranged from 0.5 mg/L to 2 mg/L by the BMD method and from 1 mg/L to >16 mg/L by the Etest method, and AmBisome MICs ranged from 0.06 mg/L to >16 mg/L by the BMD method. Etest appears to be superior to the CLSI BMD method using AmB in detecting AmB resistance of Aspergillus spp., although the CLSI BMD method might be a suitable procedure if AmBisome is used as the test drug.


Ameliorative potential of sitagliptin and/or resveratrol on experimentally-induced clear cell renal cell carcinoma.
The aim of this study was to assess the effect of sitagliptin with or without resveratrol on carcinogen-induced clear cell renal cell carcinoma. Sixty male Wistar rats were divided into 6 equal groups as follows: control; clear cell renal cell carcinoma group; clear cell renal cell carcinoma+sitagliptin group; clear cell renal cell carcinoma+resveratrol group; clear cell renal cell carcinoma+carboxymethyl cellulose group and clear cell renal cell carcinoma+sitagliptin+resveratrol group. Blood urea, serum creatinine, creatinine clearance, urinary N-acetyl beta-d-glucosaminidase (NAG), gamma glutamyl transpeptidase (GGT) and urinary albumin excretion rate (UAER) were determined. Renal tissue antioxidant enzymes, lactate dehydrogenase (LDH), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase-1 (HO-1), transforming growth factor beta-1 (TGF-β1), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and signal transducers and activators of transcription-3 (STAT3) were determined. Parts of the kidneys were subjected to histopathological and immunohistochemical examination for nuclear factor kappa B (p65). Sitagliptin and/or resveratrol induced significant improvement of the renal functions with significant increase in tissue antioxidant defenses and Nrf2/HO-1 content associated with significant decrease in tissue LDH, TGF-β1, TNF-α, IL-6 and STAT3 and alleviated the histopathological and immunohistochemical changes compared to the untreated clear cell renal cell carcinoma group. These effects were significant in sitagliptin/resveratrol combination group compared to the use of each of these drugs alone. In conclusion, sitagliptin/resveratrol combination might represent a beneficial therapeutic modality for amelioration of experimentally-induced clear cell renal cell carcinoma.


Clinical evaluation of cefotaxime for therapy of lower respiratory tract infections.
A clinical trial was designed to evaluate the efficacy and safety of cefotaxime, a new semisynthetic, broad-spectrum cephalosporin, in the therapy of community-and hospital-acquired pneumonias. Thirty-nine males (mean age, 65 years) were treated for 41 episodes of pneumonia. Only five patient did not have a serious underlying disease; 15 had two or more significant disorders. Sixty-six percent of these pneumonias were due to Streptococcus pneumoniae or Haemophilus influenzae. The minimal inhibitory concentrations for all bacterial isolates ranged from 0.008 to 4 micrograms/ml. Peak serum cefotaxime levels during therapy ranged from 12 to 124 micrograms/ml 1 h after a 1-g dose. Satisfactory bacteriological and clinical responses were observed in 85% of the cases. Four episodes of pulmonary superinfections due to cefotaxime-resistant gram-negative bacilli were noted, each in a patient being mechanically ventilated. Pseudomonas was involved in each of these superinfections, and three were fatal. No serious toxicity or adverse reaction to cefotaxime was seen. The results of this study suggest that cefotaxime is an affective and well-tolerated new cephalosporin antimicrobial agent for the therapy of pneumonia due to susceptible organisms.


Effectiveness of antiretroviral therapy and development of drug resistance in HIV-1 infected patients in Mombasa, Kenya.
Access to antiretroviral therapy (ART) is increasing in resource-limited settings (RLS) and can successfully reduce HIV-related morbidity and mortality. However, virologic failure and development of viral drug resistance can result in reduced treatment options and disease progression. Additionally, transmission of resistant virus, and particularly multi-drug resistance, could become a public health concern. This study evaluated treatment success and development of ART drug resistance after short-term treatment among patients attending the Comprehensive HIV Care Centre (CCC) of Coast Province General Hospital, Mombasa, Kenya. One hundred and fifty HIV-infected individuals receiving ART were consecutively recruited to participate in the study. After determination of plasma viral load, patients with detectable viral load levels were subjected to genotypic drug resistance testing. At the time of sampling, 132 of the 150 participants were on ART for more than 6 months (median 21 months, IQR = 12-26). An efficient viral load reduction to below 50 copies/ml was observed in 113 (85.6%) of them. Of the 19 patients with a detectable viral load, sequencing of the protease (PR) and reverse transcriptase (RT) gene was successful in 16. Eleven (11) of these 16 patients were infected with a subtype A1 virus. Major PR mutations were absent, but mutations associated with drug resistance in RT were detected in 14 of the 16 patients (87.5%). High-level resistance against at least 2 drugs of the ART regimen was observed in 9/14 (64.3%). The 3TC mutation M184V and the NNRTI mutation K103N were most frequent but also the multi-drug resistance Q151M and the broad NRTI cross-resistance K65R were observed. The results of this study revealed a high rate of treatment success after short term ART in patients treated at a public provincial hospital in a RLS. Nevertheless, the observed high risk of accumulation of resistance mutations among patients failing treatment and the selection of multi-drug resistance mutations in some, remains of great concern for future treatment options and potential transmission to partners.


Effect of reduced pH on physiology and shell integrity of juvenile Haliotis iris (pāua) from New Zealand.
The New Zealand pāua or black footed abalone, Haliotis iris, is one of many mollusc species at potential risk from ocean acidification and warming. To investigate possible impacts, juvenile pāua (~24 mm shell length) were grown for 4 months in seawater pH/pCO2 conditions projected for 2100. End of century seawater projections (pHT 7.66/pCO2 ~1,000 μatm) were contrasted with local ambient conditions (pHT 8.00/pCO2 ~400 μatm) at two typical temperatures (13 and 15 °C). We used a combination of methods (morphometric, scanning electron microscopy, X-ray diffraction) to investigate effects on juvenile survival and growth, as well as shell mineralogy and integrity. Lowered pH did not affect survival, growth rate or condition, but animals grew significantly faster at the higher temperature. Juvenile pāua were able to biomineralise their inner nacreous aragonite layer and their outer prismatic calcite layer under end-of-century pH conditions, at both temperatures, and carbonate composition was not affected. There was some thickening of the nacre layer in the newly deposited shell with reduced pH and also at the higher temperature. Most obvious was post-depositional alteration of the shell under lowered pH: the prismatic calcite layer was thinner, and there was greater etching of the external shell surface; this dissolution was greater at the higher temperature. These results demonstrate the importance of even a small (2 °C) difference in temperature on growth and shell characteristics, and on modifying the effects at lowered pH. Projected CO2-related changes may affect shell quality of this iconic New Zealand mollusc through etching (dissolution) and thinning, with potential implications for resilience to physical stresses such as predation and wave action.


microRNA-29 negatively regulates EMT regulator N-myc interactor in breast cancer.
N-Myc Interactor is an inducible protein whose expression is compromised in advanced stage breast cancer. Downregulation of NMI, a gatekeeper of epithelial phenotype, in breast tumors promotes mesenchymal, invasive and metastatic phenotype of the cancer cells. Thus the mechanisms that regulate expression of NMI are of potential interest for understanding the etiology of breast tumor progression and metastasis. Web based prediction algorithms were used to identify miRNAs that potentially target the NMI transcript. Luciferase reporter assays and western blot analysis were used to confirm the ability of miR-29 to target NMI. Quantitive-RT-PCRs were used to examine levels of miR29 and NMI from cell line and patient specimen derived RNA. The functional impact of miR-29 on EMT phenotype was evaluated using transwell migration as well as monitoring 3D matrigel growth morphology. Anti-miRs were used to examine effects of reducing miR-29 levels from cells. Western blots were used to examine changes in GSK3β phosphorylation status. The impact on molecular attributes of EMT was evaluated using immunocytochemistry, qRT-PCRs as well as Western blot analyses. Invasive, mesenchymal-like breast cancer cell lines showed increased levels of miR-29. Introduction of miR-29 into breast cancer cells (with robust level of NMI) resulted in decreased NMI expression and increased invasion, whereas treatment of cells with high miR-29 and low NMI levels with miR-29 antagonists increased NMI expression and decreased invasion. Assessment of 2D and 3D growth morphologies revealed an EMT promoting effect of miR-29. Analysis of mRNA of NMI and miR-29 from patient derived breast cancer tumors showed a strong, inverse relationship between the expression of NMI and the miR-29. Our studies also revealed that in the absence of NMI, miR-29 expression is upregulated due to unrestricted Wnt/β-catenin signaling resulting from inactivation of GSK3β. Aberrant miR-29 expression may account for reduced NMI expression in breast tumors and mesenchymal phenotype of cancer cells that promotes invasive growth. Reduction in NMI levels has a feed-forward impact on miR-29 levels.


Item-level informant discrepancies across obese-overweight children and their parents on the PedsQL™ 4.0 instrument: an iterative hybrid ordinal logistic regression.
Child obesity has become a major health concern worldwide. In order to provide successful intervention strategies, it is necessary to understand how obese-overweight children and their parents perceive obesity and its consequences on child's health-related quality of life (HRQoL). This study aimed to assess measurement equivalence of the PedsQL™ 4.0 across obese-overweight children and their parents. The items in the PedsQL™ 4.0 were analysed for differential item functioning (DIF) across obese-overweight children and their parents using an iterative hybrid ordinal logistic regression/item response theory approach. The sample included 647 overweight-obese children and their parents, who completed child and parent reports of the PedsQL™ 4.0, respectively. Overall, 17 out of 23 (74%) items were flagged with DIF across two groups: eight items exhibited uniform DIF and nine items non-uniform DIF. In addition, parents of obese children rated the child's HRQoL significantly lower than their children in all domains of the PedsQL™ 4.0, and this finding did not change whether or not items with uniform DIF were included. Although obese-overweight children and their parents interpret items of the PedsQL™ 4.0 in a conceptually different manner, removing or retaining DIF items in the subscales had no significant effects on group differences. Accordingly, it appears that observed differences in HRQoL scores across child and parent reports are a true difference and not a reflection of measurement artefact.


Relations between scatter factor, quality index and attenuation for x-ray beams.
The relations between the attenuation factor, the normalized phantom scatter factor and the quality index are examined using a semiempirical formula for the dose on the central axis of an x-ray beam in water. The study is restricted to depths and field sizes sufficient for electron equilibrium. The results are compared with data in the recent literature. It is concluded that for x-ray beams in the energy range 4-25 MV the normalized scatter factors can be calculated from the dose-weighted average linear attenuation coefficient in water, determined from transmission measurements in a narrow-beam geometry or from the quality index.


Analysis of the hemodynamic characteristics of brain arteriovenous malformations using electrical models: baseline settings, surgical extirpation, endovascular embolization, and surgical bypass.
The goal of this report is to analyze the hemodynamic characteristics of low- and high-flow arteriovenous malformations (AVM) using computerized electrical models. Two electrical models of brain AVMs were created. These models consist of electrical resistors that simulate AVM vessels. In both models, a low-flow AVM and a high-flow AVM, the flow of electrons simulates the flow of blood. Using the models, it was possible to analyze the pressure and flow patterns in the nidus of the small, low-flow AVM and in the nidus of the large, high-flow AVM. Baseline hemodynamic "physiological" conditions of the two AVMs were studied. With the models, it was also possible to assess the AVM hemodynamic changes (in the feeding arteries, in the various parts of the nidus, and in the draining veins) after surgery, after embolization, and after surgical bypass of the malformation. The role of autoregulation in the three treatment modalities was also assessed. These electrical models seem to be useful in simulating and studying the behavior of flow and pressure in the different parts of the AVM nidus (arterial, arteriolar, arteriolar-venular, venular, venous) before and after treatment. The models can also be used to devise and simulate new treatment strategies that might lead to improved treatment of these highly complex vascular malformations of the brain.


Sodium-containing versus sodium-trace preparations of IVIG for children with Kawasaki disease in the acute phase.
Kawasaki disease (KD) is an acute systemic vasculitis that most commonly causes acquired cardiac disease in children in developed countries. The most highly recommended treatment for KD is 2 g/kg intravenous immunoglobulin (IVIG). There are two types of IVIG, sodium-containing (high-Na) and sodium-trace (low-Na) preparations. However, few studies have compared the effects of these two preparations for superiority. The purpose of this study was to compare outcomes between high and low-Na IVIG preparations in KD children using a national inpatient database in Japan. We used the Diagnostic Procedure Combination database to identify KD patients treated with IVIG between 2010 and 2017. We identified those receiving high and low-Na preparations of IVIG as an initial treatment. Outcomes included proportion of coronary artery abnormalities (CAA), IVIG resistance, adverse effects, length of stay, and medical cost. Propensity score-matched analyses were conducted to compare the outcomes between the two groups. Instrumental variable analyses were performed to confirm the results. We identified 42,345 patients with KD. There were significant differences in proportions of CAA (2.8% vs. 3.2%; p = 0.031) and IVIG resistance (17% vs. 18%, p = 0.001) between the two groups. However, there were no significant differences in length of stay or medical cost. The instrumental variable analysis confirmed the same results as the propensity score analysis.Conclusion: The present study suggests that high-Na IVIG is potentially effective for reducing the proportion of CAA in KD patients. Prospective studies are warranted to confirm the effectiveness observed in this study. What is Known: • For treatments of Kawasaki Disease in acute phase, intravenous immunoglobulin have been the most recommended to reduce fever early and prevent complications of coronary artery abnormalities. There are two types of IVIG preparations, sodium-containing IVIG and sodium-trace IVIG. However, few studies have performed comparisons to determine which preparation of IVIG is superior. What is New: • The present findings suggest that high-Na IVIG is associated with reductions in the proportions of CAAs and IVIG resistance in KD patients.


Examining trust in health professionals among family caregivers of nursing home residents with advanced dementia.
In a context of increasing emphasis on shared decision-making and palliative care in dementia, research on family caregivers' trust in health professionals in advanced dementia is surprisingly scant. The aim of the present study was to assess trust in nursing home health professionals of family caregivers of nursing home residents with advanced dementia, and possible correlates, such as family caregivers' satisfaction, involvement in care, care burden and patients' symptom burden. A cross-sectional study was carried out using structured questionnaires administered through the telephone. Generalized estimating equation analyses with adjustment for nursing home clustering were applied to assess the most important associations with family caregivers' trust. A total of 214 family caregivers of persons with dementia residing in 25 nursing homes participated in the study. The majority of the participants (67%) were women and adult children (75%). The majority of the family caregivers trusted physicians, nurses and nurses' aides at a moderate-to-high level. Approximately half to one-third reported moderate-to-low levels of trust. Higher levels of trust were associated with more positive care outcomes, such as higher family satisfaction with care and more positive evaluations of physician-family communication. The present study showed the importance of family caregivers trusting nursing home health professionals for their experiences as caregivers. Although causation cannot be established, increased family caregivers' trust in nursing home health professionals by improving communication and exchange of information might provide a good basis for providing optimal palliative care in advanced dementia. Geriatr Gerontol Int 2017; 17: 2466-2471.


Public-private partnerships in the response to HIV: experience from the resource industry in Papua New Guinea.
Although Papua New Guinea (PNG) has made some progress in social development over the past 30 years, the country's Human Development Index has slowed in recent years, placing it below the regional average. In 2012, the estimated HIV prevalence for adults aged 15-49 years was 0.5% and an estimated 25,000 people were living with HIV. Although reduced from previous estimates, the country's HIV prevalence remains the highest in the South Pacific region. While the faith-based and non-governmental sectors have engaged in HIV interventions since the epidemic began, until recently the corporate sector has remained on the margins of the national response. In 2008, the country's largest oil and gas producer began partnering with national and provincial health authorities, development partners and global financing institutions to contribute to the national HIV strategy and implementation plan. This article provides an overview of public-private partnerships (PPPs) and their application to public health program management, and then describes the PPP that was developed in PNG. Innovative national and local PPPs have become a core component of healthcare strategy in many countries. PPPs have many forms and their use in low- and middle-income countries has progressively demonstrated increased service outputs and health outcomes beyond what the public sector alone could achieve. A PPP in PNG has resulted in an oil and gas producer engaging in the response to HIV, including managing the country's US$46 million HIV grant from the Global Fund to Fight AIDS, Tuberculosis and Malaria. Given the increasing expectations of the international community in relation to corporate responsibility and sustainability, the role of the corporate sector in countries like PNG is critical. Combining philanthropic investment with business strategy, expertise and organisational resource can contribute to enhancing health system structures and capacity.


A community approach of pathogens and their arthropod vectors (ticks and fleas) in dogs of African Sub-Sahara.
Arthropod-borne pathogens and their vectors are present throughout Africa. They have been well-studied in livestock of sub-Saharan Africa, but poorly in companion animals. Given the socio-economic importance of companion animals, the African Small Companion Animal Network (AFSCAN), as part of the WSAVA Foundation, initiated a standardized multi-country surveillance study. Macro-geographic variation in ectoparasite (ticks and fleas) and pathogen communities in dogs was assessed through molecular screening of approximately 100 infested dogs in each of six countries (Ghana, Kenya, Nigeria, Tanzania, Uganda and Namibia), both in rural and urban settings. The most important intrinsic and extrinsic risk factors within the subpopulation of infested dogs were evaluated. Despite the large macro-geographic variation in the dogs screened, there was no consistent difference between East and West Africa in terms of the diversity and numbers of ticks. The highest and lowest numbers of ticks were found in Nigeria and Namibia, respectively. Most often, there was a higher diversity of ticks in rural habitats than in urban habitats, although the highest diversity was observed in an urban Uganda setting. With the exception of Namibia, more fleas were collected in rural areas. We identified tick species (including Haemaphysalis spinulosa) as well as zoonotic pathogens (Coxiella burnetti, Trypanosoma spp.) that are not classically associated with companion animals. Rhipicephalus sanguineus was the most abundant tick, with a preference for urban areas. Exophilic ticks, such as Haemaphysalis spp., were more often found in rural areas. Several multi-host ticks occurred in urban areas. For R. sanguineus, housing conditions and additional pets were relevant factors in terms of infestation, while for a rural tick species (Haemaphysalis elliptica), free-roaming dogs were more often infested. Tick occurrence was associated to the use of endoparasiticide, but not to the use of ectoparasiticide. The most prevalent tick-borne pathogen was Hepatozoon canis followed by Ehrlichia canis. High levels of co-parasitism were observed in all countries and habitats. As dogs share a common environment with people, they have the potential to extend the network of pathogen transmission to humans. Our study will help epidemiologists to provide recommendations for surveillance and prevention of pathogens in dogs and humans.


Multilayer thin-film inspection through measurements of reflection coefficients.
A vibration-insensitive interferometer is described to measure the thickness, refraction index and surface profile of thin-film stack at normal incidence. By satisfying the continuous boundary conditions of electric and magnetic fields at interfaces in a multilayer film stack, the reflection coefficient phase of the thin-film stack can be distinguished from the phase of spatial path difference, thus thickness and refraction index can be extracted. The experiment results showed that the measurement precision is significantly increased after the phase analysis was added into the reflectance analysis.


Prevention by anti-LFA-1 of acute myoblast death following transplantation.
Myoblast transplantation is a potential treatment for Duchenne muscular dystrophy. One of the problems possibly responsible for the limited success of clinical trials is the rapid death of the myoblasts after transplantation. To investigate this problem, myoblasts expressing beta-galactosidase were injected in the tibialis anterior muscles of mice. Beta-galactosidase activity was reduced by 74.7% after 3 days. Myoblast death observed at 3 days was reduced to 57.2% when the hosts were irradiated. This result suggested that host cells were contributing to this phenomenon. Transplantation in SCID and FK506-treated mice did not reduce cell death, indicating that mortality was not due to an acute specific reaction. In contrast, administration of the anti-LFA-1 (TIB-213) mAb markedly reduced myoblast death at 3 days without altering leukocyte tissue infiltration. We postulated that neutrophils were mediating myoblast mortality by an LFA-1-dependent mechanism. To test this hypothesis, IL-1beta-activated myoblasts were loaded with 6-carboxy-2',7'-dichlorodihydrofluorescein diacetate, di(acetoxymethylester) (DCFH), a marker for oxidative stress. Addition of neutrophils and zymosan-activated serum resulted in a time-dependent DCFH fluorescence; this neutrophil-induced oxidation was considerably inhibited by TIB-213. These results indicate that an effective control of the inflammatory reaction will be necessary for any new clinical trials of myoblast transplantation and suggest that neutrophil-mediated myoblast injury occurs by an LFA-1-dependent pathway.


Thermochemical transformation of sulfur compounds in Japanese domestic Allium, Allium victorialis L.
Sulfur compounds contributed to the health promotion in Allium species are produced via enzymic and thermal reactions. Potent antithrombotic agents which have been identified as allyl trisulfides, dithiins, and ajoene in garlic (A. sativum) and caucas (A. victorialis) are thermochemically transformed from allicin (allyl 2-propenethiosulfinate). The leaves and stems of Japanese domestic Allium plant, A. victorialis L. which is widely distributed in the northern part of Japan, under the name "Gyoja-ninniku" is a nutritious vegetable. The significant flavor compounds of caucas are methyl allyl disulfide (Chinese chive odor), diallyl disulfide (garlic-like odor), and dimethyl disulfide and methyl allyl trisulfide (pickles-like odor) among more than 85 peaks on the gas chromatogram. 2-Vinyl-4H-1,3-dithiin and 3,4-dihydro-3-vinyl-1,2-dithiin as platelet aggregation inhibitors were found eliminated in dichloromethane extract of caucas. The significant health promoting factors, allyl trisulfides and dithiins were relatively increased when caucas was cooked on a frying pan.


Thermodynamic stability, kinetic inertness and relaxometric properties of monoamide derivatives of lanthanide(III) DOTA complexes.
A complete thermodynamic and kinetic solution study on lanthanide(III) complexes with monoacetamide (DOTAMA, L1) and monopropionamide (DOTAMAP, L2) derivatives of DOTA (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) was undertaken with the aim to elucidate their stability and inertness in aqueous media. The stability constants of GdL1 and GdL2 are comparable, whereas a more marked difference is found in the kinetic inertness of the two complexes. The formation of the Eu(III) and Ce(III) complexes takes place via the formation of the protonated intermediates which can deprotonate and transform into the final complex through a OH(-) assisted pathway. GdL2 shows faster rates of acid catalysed decomplexation with respect to GdL1, which has a kinetic inertness comparable to GdDOTA. Nevertheless, GdL2 is one order of magnitude more inert than GdDO3A. A novel DOTAMAP-based bifunctional chelating ligand and its deoxycholic acid derivative (L5) were also synthesized. Since the coordinated water molecule in GdL2 is characterized by an exchange rate ca. two orders of magnitude greater than in GdL1, the relaxivity of the macromolecular derivatives of L5 should not be limited by the slow water exchange process. The relaxometric properties of the supramolecular adduct of GdL5 with human serum albumin (HSA) were investigated in aqueous solution by measuring the magnetic field dependence of the (1)H relaxivity which, at 20 MHz and 298 K, shows a 430% increase over that of the unbound GdL5 chelate. Thus, Gd(III) complexes with DOTAMAP macrocyclic ligands can represent good candidates for the development of stable and highly effective bioconjugate systems for molecular imaging applications.


Effects of suboptimal levels of extracellular calcium on the regulation of the cyclic AMP phosphodiesterase-inhibitor system and membrane differentiation in Dictyostelium discoideum.
When starved wild-type amoebae of Dictyostelium discoideum were washed and incubated in 1 mM-EGTA, their ability to induce soluble cyclic AMP phosphodiesterase (PD) activity in response to either millimolar cyclic AMP or a series of nanomolar cyclic AMP pulses was reduced by 55-75%. Supplementation of EGTA-treated cells with exogenous Ca2+ stimulated PD induction in a dose-dependent fashion (EC50 = 100-200 nM free extracellular Ca2+), and enzyme production was maximal at about 1 microM free Ca2+. Ca2+ depletion also strongly impaired production of the phosphodiesterase inhibitor (PDI). In contrast, other than delaying their appearance by about 1 h, EGTA had little effect on the induction by cyclic AMP pulses of cell surface markers such as contact sites A and membrane-bound PD activity. Similar changes in both the soluble and membrane activities were observed with strain NP368, a mutant that overproduces cyclic GMP when stimulated by cyclic AMP. Thus, Ca2+ depletion does not appear to inhibit PD and PDI production by reducing intracellular cyclic GMP. To determine whether Ca2+ depletion alters signal transduction, two mutants that produce the soluble PD activities constitutively were examined. Suboptimal concentrations of free extracellular Ca2+ were found to inhibit PD production in these cells to the same degree and with the same concentration dependence as low Ca2+ inhibited PD induction by cyclic AMP in wild-type cells. These results suggest that Ca2+ depletion by EGTA probably inhibits PD and PDI production indirectly by perturbing an intracellular Ca2+ pool(s) rather than by altering a surface cyclic AMP-receptor-mediated process.


Modulation of the endocannabinoid system by lipid rafts.
Endocannabinoids like anandamide and 2-arachidonoylglycerol bind and activate type-1 (CB1R) and type-2 (CB2R) cannabinoid receptors, two inhibitory G protein-coupled receptors (GPCRs) that are localized in the central nervous system and in peripheral tissues. The biological actions of these lipids are controlled through not yet fully characterized cellular mechanisms that regulate the release of endocannabinoids from membrane precursors, their uptake by cells, and their intracellular disposal. The transport of anandamide through the plasma membrane is saturable and energy-independent, and might occur through a putative anandamide membrane transporter. Altogether anandamide and 2-arachidonoylglycerol, their congeners and the proteins that bind, transport, synthesize and hydrolyze these lipids, form the "endocannabinoid system". Accumulating evidence shows that CB1R (but not CB2R) binding and signaling, as well as anandamide transport, are under the control of lipid rafts (LRs), plasma membrane subdomains which modulate the activity of a number of GPCRs. Here we summarize the main features of the endocannabinoid system and LRs, in order to put the functional and structural effects of LRs on CB receptors, AEA transport and endocannabinoid signaling in a better focus. We outline the structural determinants that might explain the differential sensitivity of cannabic receptors towards raft integrity, and propose a general model to explain the dependence of endocannabinoid system on LRs. Finally, we also discuss the possible exploitation of LRs-targeted drugs as novel therapeutics for the treatment of endocannabinoid system-related pathologies.


pKa shifting in double-stranded RNA is highly dependent upon nearest neighbors and bulge positioning.
Shifting of pKa's in RNA is important for many biological processes; however, the driving forces responsible for shifting are not well understood. Herein, we determine how structural environments surrounding protonated bases affect pKa shifting in double-stranded RNA (dsRNA). Using (31)P NMR, we determined the pKa of the adenine in an A(+)·C base pair in various sequence and structural environments. We found a significant dependence of pKa on the base pairing strength of nearest neighbors and the location of a nearby bulge. Increasing nearest neighbor base pairing strength shifted the pKa of the adenine in an A(+)·C base pair higher by an additional 1.6 pKa units, from 6.5 to 8.1, which is well above neutrality. The addition of a bulge two base pairs away from a protonated A(+)·C base pair shifted the pKa by only ~0.5 units less than a perfectly base paired hairpin; however, positioning the bulge just one base pair away from the A(+)·C base pair prohibited formation of the protonated base pair as well as several flanking base pairs. Comparison of data collected at 25 °C and 100 mM KCl to biological temperature and Mg(2+) concentration revealed only slight pKa changes, suggesting that similar sequence contexts in biological systems have the potential to be protonated at biological pH. We present a general model to aid in the determination of the roles protonated bases may play in various dsRNA-mediated processes including ADAR editing, miRNA processing, programmed ribosomal frameshifting, and general acid-base catalysis in ribozymes.


Annealing temperature effect on self-assembled Au droplets on Si (111).
We investigate the effect of annealing temperature on self-assembled Au droplets on Si (111). The annealing temperature is systematically varied while fixing other growth parameters such as deposition amount and annealing duration clearly to observe the annealing temperature effect. Self-assembled Au droplets are fabricated by annealing from 50°C to 850°C with 2-nm Au deposition for 30 s. With increased annealing temperatures, Au droplets show gradually increased height and diameter while the density of droplets progressively decreases. Self-assembled Au droplets with fine uniformity can be fabricated between 550°C and 800°C. While Au droplets become much larger with increased deposition amount, the extended annealing duration only mildly affects droplet size and density. The results are systematically analyzed with cross-sectional line profiles, Fourier filter transform power spectra, height histogram, surface area ratio, and size and density plots. This study can provide an aid point for the fabrication of nanowires on Si (111).


Single-Atom Ru Catalyst-Decorated CNF(ZnO) Nanocages for Efficient H2 Evolution and CH3OH Production.
The presence of transition-metal single-atom catalysts effectively enhances the interaction between the substrate and reactant molecules, thus exhibiting extraordinary catalytic performance. In this work, we for the first time report a facile synthetic procedure for placing highly dispersed Ru single atoms on stable CNF(ZnO) nanocages. We unravel the atomistic nature of the Ru single atoms in CNF(ZnO)/Ru systems using advanced HAADF-STEM, HRTEM, and XANES analytical methods. Density functional theory calculations further support the presence of ruthenium single-atom sites in the CNF(ZnO)/Ru system. Our work further demonstrates the excellent photocatalytic ability of the CNF(ZnO)/Ru system with respect to H2 production (5.8 mmol g-1 h-1) and reduction of CO2 to CH3OH [249 μmol (g of catalyst)-1] with apparent quantum efficiencies of 3.8% and 1.4% for H2 and CH3OH generation, respectively. Our studies unambiguously demonstrate the presence of atomically dispersed ruthenium sites in CNF(ZnO)/Ru catalysts, which greatly enhance charge transfer, thus facilitating the aforementioned photocatalytic redox reactions.


Clinical trials of classical homeopathy: reflections on appropriate research designs.
The growing popularity of complementary medicine has been accompanied by a call for controlled clinical studies to examine the efficacy and validity of its various methods. The difficulties encountered in applying the evaluation methods of conventional medicine to complementary medicine are the result of the different paradigms underlying these two methods of medicine, and the differences in the healing process. This paper attempts to bridge the gap between these two approaches and to suggest a possibility to use conventional research methodology in clinical studies of classical homeopathy. Two methods are described. One is the randomization into a placebo or a treatment group after an individual remedy is chosen for each patient. This method requires an experienced homeopath and is reproducible only by the same homeopath in the same population. On the other hand, the expected success rate will be high. Another method is prescribing and treating according to so-called keynotes, a set of symptoms known to respond to a particular remedy that must be present in a patient in order to elicit a reaction from the remedy. This method is more suitable to a conventional design of a clinical study and is reproducible by anyone. Yet the expected success rate is much lower. Some general design issues that may have a particular impact on clinical trials of classical homeopathy are discussed, including the need for sufficiently powered trials to detect relatively small effects, strategies to deal with patient preference and embracing the use of "active-control" pragmatic trial designs.


Single live-cell imaging for systems biology.
Understanding how mammalian cells function requires a dynamic perspective. However, owing to the complexity of signalling networks, these non-linear systems can easily elude human intuition. The central aim of systems biology is to improve our understanding of the temporal complexity of cell signalling pathways, using a combination of experimental and computational approaches. Live-cell imaging and computational modelling are compatible techniques which allow quantitative analysis of cell signalling pathway dynamics. Non-invasive imaging techniques, based on the use of various luciferases and fluorescent proteins, trace cellular events such as gene expression, protein-protein interactions and protein localization in cells. By employing a number of markers in a single assay, multiple parameters can be measured simultaneously in the same cell. Following acquisition using specialized microscopy, analysis of multi-parameter time-lapse images facilitates the identification of important qualitative and quantitative relationships-linking intracellular signalling, gene expression and cell fate.


Influence of gestational age on death and neurodevelopmental outcome in premature infants with severe intracranial hemorrhage.
To determine whether death and/or neurodevelopmental impairment (NDI) after severe intracranial hemorrhage (ICH; grade 3 or 4) differs by gestational age (GA) at birth in extremely low birth weight (ELBW) infants. Demographic, perinatal and neonatal factors potentially contributing to NDI for ELBW infants (23 to 28 weeks gestation) were obtained retrospectively; outcome data came from the ELBW Follow-up Study. NDI was defined at 18 to 22 months corrected age as moderate/severe cerebral palsy, Bayley Scales of Infant Development II cognitive or motor score <70, and/or blindness or deafness. Characteristics of younger versus older infants with no versus severe ICH associated with death or NDI were compared. Generalized linear mixed models predicted death or NDI in each GA cohort. Of the 6638 infants, 61.8% had no ICH and 13.6% had severe ICH; 39% of survivors had NDI. Risk-adjusted odds of death or NDI and death were higher in the lower GA group. Lower GA increased the odds of death before 30 days for infants with severe ICH. Necrotizing enterocolitis (particularly surgical NEC), late onset infection, cystic periventricular leukomalacia and post-natal steroids contributed to mortality risk. NDI differed by GA in infants without ICH and grade 3, but not grade 4 ICH. Contributors to NDI in infants with severe ICH included male gender, surgical NEC and post-hemorrhagic hydrocephalus requiring a shunt. GA contributes to the risk of death in ELBW infants, but not NDI among survivors with severe ICH. Male gender, surgical NEC and need for a shunt add additional risk for NDI.


Alcohol and the heart. Intense hemodynamic changes associated with alcohol flush in orientals.
To evaluate the hemodynamic changes related to alcohol flush, the effects of ethanol intake (0.5 g/kg) were studied by echocardiography and systolic time intervals in 10 Finnish and 9 Japanese healthy volunteers. In 5 Japanese subjects, post-drink facial flush was associated with elevated blood acetaldehyde (peak levels 20-83 mumol/l) and marked cardiocirculatory stimulation. Heart rate was increased directly post ingestion by 65% (p less than 0.01), stroke index by 23% (p less than 0.05), and cardiac index by 106% (p less than 0.05). Diastolic blood pressure was simultaneously decreased by 23% (p less than 0.05), peripheral vascular resistance by 54% (p less than 0.01), and circumferential wall stress by 22% (p less than 0.05); ejection fraction was raised by 26% (p less than 0.01). The other Japanese and the Finnish subjects had no detectable acetaldehyde in blood after ethanol ingestion. The average hemodynamic alterations in them were similar in direction to the changes presented above, but quantitatively 6-10 times smaller (p less than 0.005 for each of these variables). Thus, in Orientals with genetically defective acetaldehyde oxidation, ingestion of even small amounts of alcohol evokes intense enhancement of left ventricular function, probably because of acetaldehyde-induced catecholamine release and peripheral vasodilation.


High serum and cerebrospinal fluid Ca/Mg ratio in recently hospitalized acutely depressed patients.
Calcium (Ca) and magnesium (Mg) are involved in many processes related to depression. Evaluations of serum and plasma Ca and Mg levels in depressive disorders do not show consistent results. The few studies that examined their cerebrospinal fluid (CSF) levels tended to find no differences between depressed patients and controls. Because both hypercalcemia and hypomagnesemia are associated with depression, and as Mg may function as a Ca antagonist, it is suggested that the relationship between these cations could be different in depressed patients and controls. We examined CSF and serum Ca and Mg in acutely depressed patients diagnosed as having major depressive disorder or being in a depressive episode of bipolar disorder. Controls were subjects undergoing lumbar puncture as part of an evaluation for headache or suspected meningitis and found to demonstrate no physical or mental disorder. Serum and CSF Ca/Mg ratios were found to be elevated in the depressed patients compared with the controls. A retrospective analysis of previous trials assessing serum/plasma or CSF Ca and Mg does not seem to refute the findings of this study. We further discuss our findings in their relation to the acuteness of the depressive disorders.


Influence of phosphate and silica on U(VI) precipitation from acidic and neutralized wastewaters.
Uranium speciation and physical-chemical characteristics were studied in solids precipitated from synthetic acidic to circumneutral wastewaters in the presence and absence of dissolved silica and phosphate to examine thermodynamic and kinetic controls on phase formation. Composition of synthetic wastewater was based on disposal sites 216-U-8 and 216-U-12 Cribs at the Hanford site (WA, USA). In the absence of dissolved silica or phosphate, crystalline or amorphous uranyl oxide hydrates, either compreignacite or meta-schoepite, precipitated at pH 5 or 7 after 30 d of reaction, in agreement with thermodynamic calculations. In the presence of 1 mM dissolved silica representative of groundwater concentrations, amorphous phases dominated by compreignacite precipitated rapidly at pH 5 or 7 as a metastable phase and formation of poorly crystalline boltwoodite, the thermodynamically stable uranyl silicate phase, was slow. In the presence of phosphate (3 mM), meta-ankoleite initially precipitated as the primary phase at pH 3, 5, or 7 regardless of the presence of 1 mM dissolved silica. Analysis of precipitates by U LIII-edge extended X-ray absorption fine structure (EXAFS) indicated that "autunite-type" sheets of meta-ankoleite transformed to "phosphuranylite-type" sheets after 30 d of reaction, probably due to Ca substitution in the structure. Low solubility of uranyl phosphate phases limits dissolved U(VI) concentrations but differences in particle size, crystallinity, and precipitate composition vary with pH and base cation concentration, which will influence the thermodynamic and kinetic stability of these phases.


The pattern of reproduction in female Columbian black-tailed deer, Odocoileus hemionus columbianus.
Ovarian cycles and the pattern of reproduction in female black-tailed deer in British Columbia were ascertained largely through examination of the ovaries from 444 females. Cyclic development and degeneration of single follicles of ovulatory size occurred several weeks before first ovulation. As the breeding season approached, a second or third large follicle developed in each cycle but in 48% of adult females the follicles were at different stages of maturation. Those failing to rupture at first ovulation luteinized 1 to 2 days thereafter. The first ovulation of the season, in November, never resulted in a lasting pregnancy even though some ova were penetrated by spermatozoa and began to cleave. First ovulation was apparently 'silent' in five of seven females for their ova lacked spermatozoa. Of sixty-one pregnant females, fifty-nine conceived at second ovulation; the other two conceived at subsequent ovulations more widely spaced than the 8- to 9-day interval between first and second ovulations. The synchrony of ovulatory cycles among adult females was such that half of them ovulated for the second time in a span of 7 or 8 days. Primary CL that formed after first ovulation grew to an average maximum volume of only about 45 mm3, whereas those originating at second ovulation grew to twice that size within 5 to 8 days. First generation CL shrank from 35 mm3 to 10 mm3 within 2 days. They disappeared within 18 months but corpora albicantia persisted for the life of the female. The possible ecological significance of the reproductive pattern is discussed.


Vitamin D Status, Vitamin D Receptor Polymorphisms, and Risk of Microvascular Complications Among Individuals With Type 2 Diabetes: A Prospective Study.
Evidence is limited regarding the associations between vitamin D status and microvascular complications in individuals with type 2 diabetes (T2D), among whom vitamin D deficiency or insufficiency is particularly common. In this study we aimed to prospectively investigate the associations of serum 25-hydroxyvitamin D [25(OH)D] and vitamin D receptor (VDR) polymorphisms with risk of diabetic microvascular complications. This analysis included 14,709 participants with T2D who were free of microvascular complications from the UK Biobank. Incidence of diabetic microvascular complications was ascertained via electronic health records. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs. Median serum 25(OH)D concentration was 40.7 nmol/L (interquartile range 27.5, 56.4). During a median of 11.2 years of follow-up, 1,370 people developed diabetic microvascular complications. Compared with participants with 25(OH)D <25 nmol/L, individuals with 25(OH)D ≥75 nmol/L had a multivariable-adjusted HR of 0.65 (95% CI 0.51, 0.84) for composite diabetic microvascular complications, 0.62 (0.40, 0.95) for diabetic retinopathy, 0.56 (0.40, 0.79) for diabetic nephropathy, and 0.48 (0.26, 0.89) for diabetic neuropathy. In addition, in comparisons with participants with 25(OH)D <25 nmol/L and minor allele homozygotes (TT of rs1544410 and GG of rs731236), the multivariable-adjusted HRs of composite diabetic microvascular complications were 0.54 (0.38, 0.78) and 0.55 (0.38, 0.80) for participants with serum 25(OH)D ≥50 nmol/L and major allele homozygotes (CC and AA), respectively, although no significant interaction was observed. Higher serum 25(OH)D concentrations were significantly associated with lower risk of diabetic microvascular complications, including diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy. Our findings suggest a potential beneficial role of maintaining adequate vitamin D status in the prevention of diabetic microvascular complications.


Vocabulary Knowledge Predicts Lexical Processing: Evidence from a Group of Participants with Diverse Educational Backgrounds.
Vocabulary knowledge is central to a speaker's command of their language. In previous research, greater vocabulary knowledge has been associated with advantages in language processing. In this study, we examined the relationship between individual differences in vocabulary and language processing performance more closely by (i) using a battery of vocabulary tests instead of just one test, and (ii) testing not only university students (Experiment 1) but young adults from a broader range of educational backgrounds (Experiment 2). Five vocabulary tests were developed, including multiple-choice and open antonym and synonym tests and a definition test, and administered together with two established measures of vocabulary. Language processing performance was measured using a lexical decision task. In Experiment 1, vocabulary and word frequency were found to predict word recognition speed while we did not observe an interaction between the effects. In Experiment 2, word recognition performance was predicted by word frequency and the interaction between word frequency and vocabulary, with high-vocabulary individuals showing smaller frequency effects. While overall the individual vocabulary tests were correlated and showed similar relationships with language processing as compared to a composite measure of all tests, they appeared to share less variance in Experiment 2 than in Experiment 1. Implications of our findings concerning the assessment of vocabulary size in individual differences studies and the investigation of individuals from more varied backgrounds are discussed.


Viral load in patients infected with pandemic H1N1 2009 influenza A virus.
Viral shedding profile of infections caused by the pandemic H1N1 2009 influenza A virus has not been reported. The aim of this study was to determine the viral load in different body sites. Viral loads of pandemic H1N1 virus in respiratory specimens, stool, urine, and serum were determined by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Respiratory specimens from patients with seasonal influenza were used as historical controls. Initial pre-treatment viral load were compared between these two groups. Serial respiratory specimens from patients with pandemic H1N1 virus infection were obtained for analysis of viral dynamics. Twenty-two pandemic H1N1 cases and 44 seasonal influenza historical controls were included. The mean initial viral load before oseltamivir therapy was 1.84 x 10(8) copies/ml for pandemic H1N1 virus compared with 3.28 x 10(8) copies/ml in seasonal influenza historical controls (P = 0.085). Among patients with pandemic H1N1 virus infection, peak viral load occurred on the day of onset of symptoms, and declined gradually afterwards, with no virus being detectable in respiratory specimens by RT-PCR 8 days and by culture 5 days after the onset of symptoms respectively, except in one patient. Pandemic H1N1 virus was detected in stool and in urine from 4/9 and 1/14 patients, respectively. Viral culture was also positive from the stool sample with the highest viral load. Younger age was associated with prolonged shedding in the respiratory tract and higher viral load in the stool. Data from this quantitative analysis of viral shedding may have implications for formulating infection control measures.


Evolution of new nonantibody proteins via iterative somatic hypermutation.
B lymphocytes use somatic hypermutation (SHM) to optimize immunoglobulins. Although SHM can rescue single point mutations deliberately introduced into nonimmunoglobulin genes, such experiments do not show whether SHM can efficiently evolve challenging novel phenotypes requiring multiple unforeseeable mutations in nonantibody proteins. We have now iterated SHM over 23 rounds of fluorescence-activated cell sorting to create monomeric red fluorescent proteins with increased photostability and far-red emissions (e.g., 649 nm), surpassing the best efforts of structure-based design. SHM offers a strategy to evolve nonantibody proteins with desirable properties for which a high-throughput selection or viable single-cell screen can be devised.


Computed tomographic-angiographic findings within the first five hours of cerebral infarction.
Modern management of acute stroke necessitates early diagnosis. To this end, we sought to delineate the radiographic features of focal hemispheric infarction within 5 hours of ictus. Fifty patients, ages 54-79, with ischemic strokes productive of at least hemiparesis underwent computed tomographic scanning and cerebral angiography (n = 38) or carotid ultrasound (n = 12). Radiographic lesions were characterized for location, size, and pathophysiology. Acute abnormalities, hypodensity, and mass effect were seen in 56% of scans and confirmed on a second scan 5-7 days later. Intracranial angiographic abnormalities occurred in 61% of patients: arterial occlusions in 45% and delayed arterial filling in 16%. Hemorrhagic infarctions occurred in 26% of second scans and were associated with mass effect (100%) and arterial occlusions (89%). Infarcts with hemorrhagic transformation were larger on both scans than those without (p = 0.001). Of four patients with infarctions in watershed territories on the scans, two had middle cerebral artery occlusions on angiography, thereby questioning the specificity of such scan lesions to low-flow states. We conclude that cerebral infarctions are often visible on early scans, but their locations may not be etiologically determinative. The infarcts associated with intracranial arterial occlusions (45%) were of thromboembolic origin, but, given current controversies as to the pathophysiology of lacunar and watershed infarctions, we cannot ascertain the etiology in the remainder. These findings are relevant to the new stroke therapies that require administration in the first hours after infarction.


Interprofessional Communication Patterns During Patient Discharges: A Social Network Analysis.
Optimal care delivery requires timely, efficient, and accurate communication among numerous providers and their patients, especially during hospital discharge. Little is known about communication patterns during this process. Our aim was to assess the frequency and patterns of communication between patients and providers during patient discharges from a hospital-based medicine unit. On the day of the patient's discharge, the patient and all healthcare providers involved in the discharge were interviewed using structured questions related to information exchange during the discharge process. Each interview identified the frequency and method of communication between participants, including synchronous (e.g., face-to-face) and asynchronous (e.g., through electronic medical record) routes. Communication patterns were visually diagramed using social network analysis. Forty-six patients were screened for inclusion in the network analysis. Of those, seven patients who were fully oriented and able to complete an interview and all providers who participated in their care during the discharge were selected for inclusion in the analysis. In all, 72 healthcare professionals contributing to the discharge process were interviewed, including physicians, nurses, therapists, pharmacists, care coordinators, social workers, and nutritionists. Patients' mean age was 63, length-of-stay was 7.8 days, and most (86 %) were discharged to home. On average, 11 roles were involved with each discharge. The majority of communication was synchronous (562 events vs. 469 asynchronous events, p = 0.004). Most communication events occurred between the primary nurse and patient and the care coordinator and primary nurse (mean 3.9 and 2.3 events/discharge, respectively). Participants identified intern physicians as most important in the discharge process, followed by primary nurses and care coordinators. In patients being discharged from the medicine service, communication was more frequently synchronous, and occurred between intern physicians, primary nurses, and patients. Potential improvements in coordinating patients' discharges are possible by reorganizing systems to optimize efficient communication.


Characterization of dengue virus serotype 1 in epidemics in Porto Velho, Rondônia, in 2001-2003.
The first dengue fever epidemic in the State of Rondônia (western region of Brazil) was recorded in 1997, without laboratory confirmation. Following this, there was an epidemic in Manaus, in the neighboring State of Amazon, in 1998, in which DENV-1 and DENV-2 viruses were isolated from patients. In the present paper, the serotype characterization of the dengue virus isolated from patients with clinically suspected dengue in Porto Velho, Rondônia, between 2001 and 2003 is described. One hundred and fifty blood samples were collected between the first and fifth days of symptoms. Seventy samples of virus isolates were subjected to dengue identification by means of RT-PCR using universal primers for the NS1 gene of DENV, which amplifies a 419 bp fragment. The amplicons obtained were subjected to enzymatic digestion to characterize the viral serotypes. All the samples analyzed were DENV-1. A nucleotide sequence randomly selected from one amplicon, which was also DENV-1, presented 98% similarity to sequences from Southeast Asia that were obtained from GenBank.


Trimellitic anhydride Toxicity. A cause of acute multisystem failure.
A person exposed to trimellitic anhydride (TMA) an epoxy resin widely used in industry, experienced respiratory failure, anemia, and gastrointestinal bleeding. A lung biopsy specimen demonstrated intra-alveolar hemorrhage and damage to alveolar lining cells. The patient and six co-workers were examined. Results indicated the presence of hemolytic antibodies directed against TMA-haptenized erythrocytes, IgG, IgA, and IgM antibodies directed against TMA-erythrocyte complexes, and antibodies against TMA-human serum albumin. Antibody levels in the patient were greater than in the co-workers. The elevated antibody levels demonstrate the antigenic potential of TMA. However, the cause of the pulmonary and hematologic damage remains uncertain and may represent either immunologic or direct toxic effects of TMA. In patients with multisystem failure of this nature, occupational hazards should be added to the differential diagnosis.


Retaining zonal chondrocyte phenotype by means of novel growth environments.
The loss of phenotype in articular chondrocytes expanded in monolayer has been established as a possible contributor to the deficiencies associated with in vitro cartilage engineering and autologous cell transplantation procedures. We cultured zonal articular chondrocytes on tissue culture plastic, collagen II-coated polystyrene, and aggrecan-coated polystyrene in an effort to find a surface that can either prevent or slow the loss of phenotype. In addition, we encapsulated passaged cells in agarose to examine the effect of three-dimensional culture on redifferentiating zonal chondrocytes. We used real-time polymerase chain reaction to measure the relative gene expression levels of collagen I and II, aggrecan, and superficial zone protein over relevant passages (P0-P4). Results showed that tissue culture plastic and the collagen II-coated surface induced rapid loss of phenotype in zonal articular chondrocytes. The aggrecan-coated surface had a less detrimental effect on the chondrocytic phenotype of seeded cells, inducing gene expression characteristics comparable to those of agarose-encapsulated cells. Furthermore, when chondrocytes that had been previously passaged on a collagen II surface were placed on an aggrecan surface, the zonal cells showed a dramatic change in gene expression from fibroblastic to chondrocytic. These results indicate that a culture environment using aggrecan as a substratum or agarose as a scaffold is crucial to the development of phenotypically correct articular cartilage.


Characteristics and Obtainment Methods of Firearms Used in Adolescent School Shootings.
Within gun violence research, the types of firearms involved in US school shootings and the origins of these weapons have not been well explored. To examine the type, make, and power of firearms involved in school-related gun violence as well as the sources and methods through which adolescents obtained these weapons. This cross-sectional study used descriptive statistics and logistic regression to analyze 253 school shootings executed by 262 adolescents (aged ≤19 years) in the US from January 1, 1990, to December 31, 2016, and to calculate adjusted estimates for missing cases. The data were sourced from The American School Shooting Study (TASSS), which compiles information about these shooting events from open-source materials. Data analysis was performed from June 23, 2023, to July 20, 2023. Firearm type, make, and power. The firearm type refers to whether a weapon was a handgun, rifle, or shotgun. The firearm's make differentiates semiautomatic or fully automatic guns from other action mechanisms. The firearm's power refers to the caliber and velocity, distinguished as small, moderate, or higher power. The acquisition source captures from whom the firearm was received. The obtainment method refers to how the shooter obtained the firearm. Estimates were adjusted by total number of documents and TASSS reliability score as well as neighborhood demographic, socioeconomic, and land use variables measured at the census tract level, and were weighted to account for item nonresponse. A total of 262 adolescents (mean [SD] age, 16.2 [1.9] years; 256 [97.8%] male) were studied. In the adjusted analyses, handguns were the most used weapon in school shootings (85.5%; 95% CI, 80.6%-89.4%). Firearms were predominantly lower (37.0%; 95% CI, 29.9%-44.7%) or moderate (39.7%; 95% CI, 32.0%-47.8%) in power. Adolescents mainly obtained their guns from relatives (41.8%; 95% CI, 31.7%-52.6%), friends or acquaintances (22.0%; 95% CI, 13.2%-34.5%), the illegal market (29.6%; 95% CI, 19.3%-42.5%), strangers or persons who were shot (4.7%; 95% CI, 1.8%-11.6%), or licensed dealers (1.9%; 95% CI, 0.7%-5.2%). Most firearms were procured via theft from relatives (82.1%; 95% CI, 69.4%-90.3%). Despite the more frequent use of lower to moderately powered firearms in school shootings, this study's results indicated stability in the use of high-powered weapons in adolescent school shootings throughout the research timeframe. A majority of the firearms were procured from the perpetrator's family or relatives or from friends or acquaintances. These findings may significantly influence discussions around gun control policy, particularly in advocating for secure firearm storage to reduce adolescents' access to weapons.


Antioxidant activity of yellow dock (Rumex crispus L., Polygonaceae) fruit extract.
The methanol extract of ripe Rumex crispus L. fruits was evaluated for its antioxidant potential by assays for ferric-reducing antioxidant power (FRAP), DPPH-free radical scavenging activity (DPPH) and the influence on lipid peroxidation in liposomes (LP). Considerable activity was observed in all test systems (FRAP: 9.9 mmol Fe(2+) /g; DPPH IC(50) : 3.7 μg/mL; LP IC(50) : 4.9 μg/mL), comparable to that of BHT (FRAP: 8.0 μg/mL; DPPH IC(50) : 19.4 μg/mL; LP IC(50) : 3.5 μg/mL), but lower than the activity of ascorbic acid, rutin and quercetin, used as positive control substances. The in vivo effects were evaluated in several hepatic antioxidant systems (activities of LPx, GSH-Px, Px, CAT and XOD, as well as GSH content), after treatment with the studied yellow dock extract in different doses, or in combination with carbon tetrachloride (CCl(4) ). Pretreatment with the R. crispus extract inhibited CCl(4) -induced oxidative stress by decreasing LPx and increasing GSH content in a dose dependent manner, bringing the levels of antioxidant enzymes to near control values.


Tailored growth of graphene oxide liquid crystals with controlled polymer crystallization in GO-polymer composites.
Graphene Oxides (GOs) have been frequently employed as fillers in polymer-based applications. While GO is known to nucleate polymer crystallization in GO-polymer composites reinforcing the mechanical properties of semicrystalline polymers, its counter effect on how polymer crystallization can alter the microstructure of GO has rarely been systematically studied yet. In this work, we study the GO nematic liquid crystal (LC) phase during polymer crystallization focusing on their hierarchical structures by employing in situ small/wide-angle X-ray scattering/diffraction (SAXS/WAXD) techniques. We found that GO LC and polymer crystals co-exist in the GO/polymer complex, where the overall liquid crystallinity is influenced by polymer crystallization. While polymer crystallizes in bulk or at the interface depending on the cooling rate, the interfacial crystallization of poly(ethylene glycol) (PEG) on GO improves both GO alignment and orientation of PEG crystal. This work provides an opportunity to develop a hierarchical structure of GO-based crystalline polymer nanocomposites, whose directionality can be controlled by polymer crystallization under proper cooling rates.


[Late-onset neutropenia following rituximab therapy as a treatment of diffuse large B-cell lymphoma: a single institution study].
Late-onset neutropenia (LON) following rituximab therapy has been reported in recent years. However, its incidence has not been reported in Korea. The aim of this study is to investigate the incidence of LON after rituximab therapy in Korean patients with diffuse large B-cell lymphoma (DLBCL). Ninety-eight cases of DLBCL treated with rituximab between 2004 and 2008 were evaluated. We identified LON as defined by the neutrophil count of <1.5 × 10(9)/L without apparent cause after the recovery of neutrophil count following rituximab therapy. Bone marrow aspiration and biopsy specimens at the time of neutropenia were available for retrospective review in only 5 of the patients. LON was observed in 15 (15.3%) of the 98 patients. In the bone marrow specimens of the 5 patients, promyelocytes were relatively increased and the maturation index of the granulopoiesis was 2:1-3:1, which reflects maturation arrest. The incidence of LON following rituximab therapy was 15.3% in Korean patients with DLBCL. Although there are several hypotheses about the causative mechanisms of LON, we suggest that maturation arrest at the promyelocyte stage of granulopoiesis may be one of the mechanisms involved in the development of LON.


Mechanistic evidence in support of alpha1-antitrypsin as a therapeutic approach for type 1 diabetes.
Utilizing endogenous molecules as a therapeutic approach is almost unequivocally superior to engineered or synthetic molecules. However, one rarely encounters an anti-inflammatory, cytoprotective, immunomodulatory and wound-healing molecule that has been available for use for decades. α1-antitrypsin (AAT), a circulating protein that rises more than 4-fold during acute-phase responses, has been administered for a rare genetic deficiency at large doses, for life. Aside from advances in insulin therapy, medical research in type 1 diabetes (T1D) has predominantly focused on autoimmunity--controlling the adaptive immune response. However, it is now appreciated that one may need to extend therapeutic targets to incorporate immune responses to cellular injury, as well as promote selective control over excessive inflammation and early tissue repair. Recent data suggest that tissue damage related to lung and renal ischemia-reperfusion injury, stroke, and ischemic heart disease is markedly reduced by AAT. AAT was also shown to protect pancreatic islet β cells at multiple levels. Unlike classic immunosuppressive and anti-inflammatory approaches, AAT exerts some antiviral and antibacterial activities. Based on these and other reports, AAT is under evaluation for treatment of T1D patients in multiple clinical trials. Initial results suggest that AAT therapy could potentially improve insulin production without adverse effects. Up to 50% of individuals displayed improved islet function. It is a rare occurrence in T1D research that a therapy is offered that holds a safety profile equal or superior to that of insulin alone. While placebo-controlled trials are ongoing, the mechanism(s) behind these favorable activities of AAT are still being explored.


Risk factors and outcome of Pseudomonas aeruginosa bacteremia among adults visiting the ED.
The aim of this study was to determine the clinical characteristics of, antibiotic therapy for, and clinical outcome of Pseudomonas aeruginosa infection among bacteremic adults who visit the emergency department (ED). Bacteremic adults who visited the ED were identified retrospectively from January 2007 to December 2007. Demographic characteristics, underlying illnesses, severity, bacteremic pathogens, antimicrobial agents, and outcome were determined from chart records. The records of 340 eligible bacteremic adults were analyzed; their mean age was 66.2 years, and major comorbidities included hypertension (175 patients, or 51.5%), diabetes mellitus (124, or 36.5%), and malignancy (87, or 25.6%). Among the 379 bacteremic isolates, Escherichia coli (139 isolates, or 6.6%) and Klebsiella pneumoniae (63, or 16.6%) were the major pathogens, whereas P aeruginosa (15, or 4.0%) was the third-leading gram-negative isolate. Of note, both 30-day mortality (33.3% vs 8.9%, P = .01) and the proportion of empirically inappropriate antibiotics (86.7% vs 31.4%, P < .001) were higher in bacteremia caused by P aeruginosa than in bacteremia not caused by P aeruginosa in univariate analysis. Moreover, multivariate analysis identified 3 independent factors related to P aeruginosa bacteremia: surgery during the 4 weeks before ED arrival (adjusted odds ratio [AOR], 12.7; 95% confidence interval [CI], 1.68-95.7; P = .01), malignancy (AOR, 4.57; 95% CI, 1.27-16.3; P = .02), and community onset (AOR, 0.14; 95% CI, 0.04-0.47; P = .002). For bacteremic adults who visited the ED, P aeruginosa was associated with a high mortality rate and a high proportion of empirically inappropriate antibiotic therapy. Identification of clinical predictors of P aeruginosa bacteremia would improve the quality of care and the use of appropriate antibiotics in the ED.


Silver diamine fluoride, atraumatic restorations, and oral health-related quality of life in children aged 5-13 years: results from the CariedAway school-based cluster randomized trial.
Silver diamine fluoride (SDF) is a non-surgical treatment for the arrest and prevention of dental caries that results in irreversible black staining of dental decay. The objective of this study was to evaluate the short-term impact of SDF treatment on oral health-related quality of life (OHRQoL) relative to a standard package of glass ionomer sealants and atraumatic restorative treatment (ART) in children aged 5-13 years. CariedAway is a pragmatic, longitudinal, cluster-randomized non-inferiority trial of non-surgical interventions for caries. Secondary study outcomes included OHRQoL and academic performance. Oral health-related quality of life was measured at each study visit using the Child Oral Health Impact Profile. Change in OHRQoL was assessed using linear regression and non-inferiority was determined using t tests. 160 children with an average age of 8.7 years completed quality of life assessments. Untreated decay at baseline (approximately 25%) was associated with significantly worse OHRQoL and treatment in both groups resulted in incremental improvement: children receiving SDF improved their OHRQoL scores from 16.44 (SD = 11.12) to 14.62 (SD = 11.90), and those receiving traditional sealants and atraumatic restorations slightly improved from 16.65 (SD = 10.56) to 16.47 (SD = 11.09). Quality of life in children receiving silver diamine fluoride was non-inferior to those receiving sealants and ART at least 6 months post-treatment (mean difference = 1.85, 95% CI = - 2.10, 5.80), and change in OHRQoL did not depend on the severity of baseline decay. OHRQoL is related to untreated dental caries, and observed changes following SDF treatment were non-inferior relative to standard preventive therapies.


PD1 negative and PD1 positive CD4+ T regulatory cells in mild cognitive impairment and Alzheimer's disease.
Regulatory T lymphocytes (Treg) play a fundamental importance in modulating the relative balance between inflammation and immune tolerance, and alterations of these cells are observed in inflammatory diseases. To better characterize the neuroinflammatory processes suggested to be associated with Alzheimer's disease (AD) and to clarify the possible role of Treg cells in this process, we extensively analyzed these cells (CD4 + CD25highFoxp3+) in patients with either severe AD (n=25) or mild cognitive impairment (MCI) (n=25), comparing the results with those of two groups of healthy controls (HC) (n=55). Because the intra- or extracellular expression of programmed death receptor 1 (PD1) identifies functionally diverse subsets of Treg we also analyzed such subpopulations. Results showed that, whereas both Treg and PD1pos Treg are increased in MCI and AD patients compared to HC, PD1neg Treg, the subpopulation of Treg cells endowed with the strongest suppressive ability, are significantly augmented in MCI patients alone. In these patients amyloid-β-stimulated-T cells proliferation was reduced and Treg-mediated suppression was more efficient compared to both AD and HC. The observation that PD1neg Treg, cells are increased in MCI patients reinforces the inflammatory origin of AD and supports a possible beneficial role of these cells in MCI that is lost in patients with full-blown AD.


Red blood cell omega-3 fatty acids and attention scores in healthy adolescents.
Omega-3 fatty acids are critical for brain function. Adolescence is increasingly believed to entail brain vulnerability to dietary intake. In contrast to the abundant research on the omega-3 docosahexaenoic acid (DHA) in cognition, research on DHA and attention in healthy adolescents is scarce. In addition, the role of alpha-linolenic acid (ALA), the vegetable omega-3 fatty acid, is unexplored. We examined associations between DHA and ALA and attention function among a healthy young population. In this cross-sectional study conducted in 372 adolescents (13.8 ± 0.9 years-old), we determined the red blood cell proportions of DHA and ALA by gas chromatography (objective biomarkers of their long-term dietary intake) and measured attention scores through the Attention Network Test. We constructed multivariable linear regression models to analyze associations, controlling for known confounders. Compared to participants at the lowest DHA tertile (reference), those at the highest DHA tertile showed significantly lower hit reaction time-standard error (higher attentiveness) (28.13 ms, 95% confidence interval [CI] = - 52.30; - 3.97), lower hit reaction time ( - 38.30 ms, 95% CI = - 73.28; - 3.33) and lower executive conflict response ( - 5.77 ms, 95% CI = - 11.44; - 0.09). In contrast, higher values were observed in those at the top tertile of ALA in hit reaction time compared to the lowest one (46.14 ms, 95% CI = 9.90; 82.34). However, a beneficial association was observed for ALA, with decreasing impulsivity index across tertiles. Overall, our results suggest that DHA (reflecting its dietary intake) is associated with attention performance in typically developing adolescents. The role of dietary ALA in attention is less clear, although higher blood levels of ALA appear to result in lower impulsivity. Future intervention studies are needed to determine the causality of these associations and to better shape dietary recommendations for brain health during the adolescence period.


Cholesterol in the plasma membrane of uterine epithelial cells: a freeze-fracture cytochemical study with digitonin.
Freeze-fracture cytochemistry with digitonin has been used to examine the cholesterol content of the plasma membrane of uterine epithelial cells during the early stages of pregnancy in the rat. Lesions caused by digitonin complexing with cholesterol were seen on both lateral and apical portions of the membrane but tight junctions and desmosomes were lesion-free. Compared with day 1 of pregnancy, lesions on the apical plasma membrane were much more extensive and some were of different morphology on day 6 - the day of blastocyst implantation. We consider mechanisms of lesion formation and interpret the results to indicate a higher content and perhaps a different organization of cholesterol in the apical plasma membrane on day 6 of pregnancy. We also suggest how this increase may occur.


Nonequilibrium roughening transition in a volume conserving system.
We introduce a simple volume conserving stochastic model undergoing a nonequilibrium roughening transition (NRT) in 1+1 dimensions. In our model, there is no deposition and evaporation of a particle breaking the volume conserving condition. The degree of roughness of the fluctuating interface in our model is determined by whether or not the hopping of a particle depends on the local slope of the interface. The hopping process of a particle is controlled by the probability 0<or=p<or=1. For p<1/2, a moving particle tends to hop in the downhill direction of the local slope of the interface, and so the interface is in a smooth phase with a zero roughness exponent. For p>1/2, a particle tends to hop in the uphill direction, and so the interface cannot reach a saturated phase. When p=1/2, the hopping of a particle does not depend on the local slope of the interface. Then the interface can reach a saturated phase. The saturated interface at p=1/2 is in a rough phase with a nonzero roughness exponent. Our model, therefore, exhibits the NRT at the critical parameter p(c)=1/2.


How to win the HIV-1 drug resistance hurdle race: running faster or jumping higher?
Infections by the human immunodeficiency virus type 1 (HIV-1), the causative agent of the acquired immunodeficiency syndrome (AIDS), are still totaling an appalling 36.7 millions worldwide, with 1.1 million AIDS deaths/year and a similar number of yearly new infections. All this, in spite of the discovery of HIV-1 as the AIDS etiological agent more than 30 years ago and the introduction of an effective combinatorial antiretroviral therapy (cART), able to control disease progression, more than 20 years ago. Although very effective, current cART is plagued by the emergence of drug-resistant viral variants and most of the efforts in the development of novel direct-acting antiviral agents (DAAs) against HIV-1 have been devoted toward the fighting of resistance. In this review, rather than providing a detailed listing of all the drugs and the corresponding resistance mutations, we aim, through relevant examples, at presenting to the general reader the conceptual shift in the approaches that are being taken to overcome the viral resistance hurdle. From the classic 'running faster' strategy, based on the development of novel DAAs active against the mutant viruses selected by the previous drugs and/or presenting to the virus a high genetic barrier toward the development of resilience, to a 'jumping higher' approach, which looks at the cell, rather than the virus, as a source of valuable drug targets, in order to make the cellular environment non-permissive toward the replication of both wild-type and mutated viruses.


Cytokine expression by first-trimester human chorionic villi.
Communication at the human maternal-fetal interface occurs by an intricate cytokine network. This study examines cytokine expression by normal first-trimester human chorionic villi. Tissues were obtained at elective pregnancy terminations (7-9 weeks). Total RNA was isolated from chorionic villi by guanidinium isothiocynate-acid phenol extraction. A reverse transcriptase-polymerase chain reaction technique was used to examine cytokine expression. beta-Actin was used as the housekeeping gene, and mitogen-stimulated lymphocytes served as positive controls. beta-Actin was uniformly expressed by all chorionic villous samples. Interferon (IFN)-alpha and -beta also were highly expressed. Moderate expression was noted for interleukin (IL)-10, IL-6, tumor necrosis factor (TNF)-alpha, and IL-1 beta. In contrast, transforming growth factor-beta 1, IFN-gamma, IL-2, and IL-1 alpha were either weakly expressed or absent in first-trimester villi. Cytokines may contribute to pregnancy immunotolerance (IFN-alpha, IFN-beta, and IL-10), viral resistance (IFNs), hormone secretion (IL-1 and IL-6), and cellular remodeling (IFN-gamma and TNF-alpha) within the chorionic villous.


The architecture of chicken chromosome territories changes during differentiation.
Between cell divisions the chromatin fiber of each chromosome is restricted to a subvolume of the interphase cell nucleus called chromosome territory. The internal organization of these chromosome territories is still largely unknown. We compared the large-scale chromatin structure of chromosome territories between several hematopoietic chicken cell types at various differentiation stages. Chromosome territories were labeled by fluorescence in situ hybridization in structurally preserved nuclei, recorded by confocal microscopy and evaluated visually and by quantitative image analysis. Chromosome territories in multipotent myeloid precursor cells appeared homogeneously stained and compact. The inactive lysozyme gene as well as the centromere of the lysozyme gene harboring chromosome located to the interior of the chromosome territory. In further differentiated cell types such as myeloblasts, macrophages and erythroblasts chromosome territories appeared increasingly diffuse, disaggregating to separable substructures. The lysozyme gene, which is gradually activated during the differentiation to activated macrophages, as well as the centromere were relocated increasingly to more external positions. Our results reveal a cell type specific constitution of chromosome territories. The data suggest that a repositioning of chromosomal loci during differentiation may be a consequence of general changes in chromosome territory morphology, not necessarily related to transcriptional changes.


Lack of prognostic value of insulin-like growth factor-1 in patients with breast cancer: analysis with tissue microarray.
Recent reports on the risk of prostate, breast, colorectal and lung cancer suggested that high circulating insulin-like growth factor-1 (IGF-1) concentrations are associated with an increased risk of cancer. The power of the tissue microarray (TMA) technique is the ability to perform a series of analyses of thousands of specimens in a parallel fashion with minimal damage to the original blocks. Archival tissue specimens from 106 patients with primary invasive breast cancer were selected and IGF-1 expression was analyzed by immunohistochemical staining of tissue microarrays. The data regarding primary tumor staging, age, estrogen receptor status, lymph node status, histological grading and TNM staging were also collected. There were 2 patients (2%) with grade 1 expression for IGF-1, 39 patients (37%) with grade 2 expression and 65 patients (61%) with grade 3 expression. There was no significant relationship between IGF-1 expression and age (p=0.256), estrogen receptor status (p=0.921), histological grading (p=0.815), primary tumor staging (p=0.455), or TNM staging (p=0.194). No survival difference was noted among the three groups with different IGF-1 expression (p=0.462). Immunohistochemical staining of the tissue microarray was convenient and feasible for the analysis of IGF-1 expression in breast cancer, yet its expression did not show any significant correlation with the overall survival rate.