Developing preventive mental health interventions for refugee families in resettlement.
In refugee resettlement, positive psychosocial outcomes for youth and adults depend to a great extent on their families. Yet refugee families find few empirically based services geared toward them. Preventive mental health interventions that aim to stop, lessen, or delay possible negative individual mental health and behavioral sequelae through improving family and community protective resources in resettled refugee families are needed. This paper describes 8 characteristics that preventive mental health interventions should address to meet the needs of refugee families, including: Feasibility, Acceptability, Culturally Tailored, Multilevel, Time Focused, Prosaicness, Effectiveness, and Adaptability. To address these 8 characteristics in the complex environment of refugee resettlement requires modifying the process of developmental research through incorporating innovative mental health services research strategies, including: resilience framework, community collaboration, mixed methods with focused ethnography, and the comprehensive dynamic trial. A preventive intervention development cycle for refugee families is proposed based on a program of research on refugees and migrants using these services research strategies. Furthering preventive mental health for refugee families also requires new policy directives, multisystemic partnerships, and research training.


Network analysis of toxin production in Clostridioides difficile identifies key metabolic dependencies.
Clostridioides difficile pathogenesis is mediated through its two toxin proteins, TcdA and TcdB, which induce intestinal epithelial cell death and inflammation. It is possible to alter C. difficile toxin production by changing various metabolite concentrations within the extracellular environment. However, it is unknown which intracellular metabolic pathways are involved and how they regulate toxin production. To investigate the response of intracellular metabolic pathways to diverse nutritional environments and toxin production states, we use previously published genome-scale metabolic models of C. difficile strains CD630 and CDR20291 (iCdG709 and iCdR703). We integrated publicly available transcriptomic data with the models using the RIPTiDe algorithm to create 16 unique contextualized C. difficile models representing a range of nutritional environments and toxin states. We used Random Forest with flux sampling and shadow pricing analyses to identify metabolic patterns correlated with toxin states and environment. Specifically, we found that arginine and ornithine uptake is particularly active in low toxin states. Additionally, uptake of arginine and ornithine is highly dependent on intracellular fatty acid and large polymer metabolite pools. We also applied the metabolic transformation algorithm (MTA) to identify model perturbations that shift metabolism from a high toxin state to a low toxin state. This analysis expands our understanding of toxin production in C. difficile and identifies metabolic dependencies that could be leveraged to mitigate disease severity.


Assessment of the histopathological lesions and chemical analysis of feral cats to the smoke from the Kuwait oil fires.
Twenty-six adult or subadult feral cats were collected from Kuwait approximately 8 months after the ignition of the Kuwait oil wells. These animals were obtained from two sources: 12 animals from Kuwait City, a relatively smoke-free area, and 14 from the city of Ahmadi, an area with heavy smoke. Animals were euthanized and a complete set of tissues consisting of all major organs was taken for histopathology. Samples of lung, liver, kidney, urine, and blood were also taken for toxicology. Histopathological lesions observed in the lung were mild accumulations of anthracotic pigment in the lungs of 17 cats. Hyperplasia of the bronchial and bronchiolar gland in 8 cats, and smooth muscle hyperplasia of bronchioles in 14 cats. Tracheal gland hyperplasia was observed in 7 cats, and minimal squamous metaplasia of the tracheal mucosa in 17 cats, Laryngeal lesions consisted of submucosal gland hyperplasia in 2 cats and squamous metaplasia of the mucosa in 5 cats. Hyperplasia of the nasal submucosal glands was observed in 6 animals. The pharyngeal mucosa as well as other organs and organ systems were normal in all cats. Atomic absorption analysis for 11 metals was performed; vanadium and nickel levels (two metals that were present in the smoke from the oil fires) are not indicative of substantial exposure to the oil fires. Based on the histopathological findings and toxicological analysis, it is felt that inhalation of air contaminated with smoke from the oil fires had little or no long-term effect on the animals examined.


Low prevalence of renal, cardiac, pulmonary, and neurological extra-articular clinical manifestations in spondyloarthritis: analysis of the Brazilian Registry of Spondyloarthritis.
To describe the extra-articular manifestations (cardiac, renal, pulmonary, and neurological), usually not related to spondyloarthritis (SpA), in a large cohort of Brazilian patients. This retrospective study analyzed 1,472 patients diagnosed with SpA and cared for at 29 health care centers distributed in the five major geographic regions in the country, participating in the Brazilian Registry of Spondyloarthritis (BRS). All patients were assessed for the prevalence of major extra-articular manifestations (cardiac, renal, pulmonary, and neurological), classified according to the diagnosis [ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis (ReA), arthritis associated with inflammatory bowel disease (IBD), undifferentiated spondyloarthritis (uSpA), and juvenile SpA], and according to the clinical presentation (axial, peripheral, mixed, and enthesitis). Of the patients with SpA assessed, 963 had AS, 271 PsA, 49 ReA, 48 arthritis associated with IBD, 98 uSpA, and 43 juvenile SpA. Cardiac involvement was reported in 44 patients (3.0%), pulmonary involvement in 19 (1.3%), renal involvement in 17 (1.2%), and neurological involvement in 13 patients (0.9%). Most patients with visceral involvement had AS or PsA, and the mixed (axial + peripheral) and/or predominantly axial clinical form. Cardiac, renal, pulmonary, and neurological extra-articular manifestations are quite infrequent in SpA, ranging from 0.9% to 3% in this large Brazilian cohort, and affected predominantly patients with AS and PsA.


Locoregional recurrence of triple-negative breast cancer: effect of type of surgery and adjuvant postoperative radiotherapy.
The aim was to evaluate the prognostic significance of postoperative radiotherapy (PORT) and surgical type on local recurrence-free survival (LRFS) and overall survival (OS) in triple-negative breast cancer (TNBC) in the Egyptian population. We evaluated 111 patients with stage I-III TNBC diagnosed at our institute during the period from 2004 to 2009. Patients were stratified according to PORT into two groups: a PORT group and a non-PORT group. The influence of PORT and surgical type on LRFS and OS were evaluated. A cross-matching was done to the non-TNBC group of patients to compare the recurrence and survival rates between them and the studied group of TNBC patients. The mean age of TNBC patients at diagnosis was 63±7 years. The majority of the patients had stage III disease (68.5%) and 73% had clinical or pathological positive lymph nodes. Sixty percent (67/111) of patients had modified radical mastectomy and 44/111 (40%) patients had breast-conserving treatment. PORT was given for 63% of patients, while systemic treatment was given in 89% of patients. At the time of analysis, 13 patients (11%) developed local recurrence: five of 70 (7%) in the PORT group and eight of 41 (19.5%) in the non-PORT group. Five-year LRFS for the whole group of patients was 88%±6%, which was significantly affected by PORT. The surgical type did not affect local recurrence significantly. Five-year OS for the whole group was 54%±8%. PORT and surgical type did not affect OS significantly (P-value 0.09 and 0.11, respectively). Five-year LRFS was 88%±6% and 90%±11% for TNBC and non-TNBC patients, respectively (P-value 0.8); however, OS for TNBC was significantly lower than for non-TNBC (P-value 0.04). TNBC is an aggressive entity compared with other non-TNBC, and these patients benefit from PORT significantly to decrease the risk of local recurrence in all stages. However, further large, prospective, randomized trials are warranted.


Array-based comparative genomic hybridization analysis of recurrent chromosome 15q rearrangements.
Genomic rearrangements of chromosome 15q11-q13 cause diverse phenotypes including autism, Prader-Willi syndrome (PWS), and Angelman syndrome (AS). This region is subject to genomic imprinting and characterized by complex combinations of low copy repeat elements. Prader-Willi and Angelman syndrome are caused primarily by 15q11-13 deletions of paternal and maternal origin, respectively. Autism is seen with maternal, but not paternal, interstitial duplications. Isodicentric 15q, most often of maternal origin, is associated with a complex phenotype often including autistic features. Limitations of conventional cytogenetic tests preclude a detailed analysis in most patients with 15q rearrangements. We have developed a microarray for comparative genomic hybridization utilizing 106 genomic clones from chromosome 15q to characterize this region. The array accurately localized all breakpoints associated with gains or losses on 15q. The results confirmed the location of the common breakpoints associated with interstitial deletions and duplications. The majority of idic(15q) chromosomes are comprised of symmetrical arms with four copies of the breakpoint 1 to breakpoint 5 region. Patients with less common breakpoints that are not distinguished by routine cytogenetic methods were more accurately characterized by array analysis. This microarray provides a detailed characterization for chromosomal abnormalities involving 15q11-q14 and is useful for more precise genotype-phenotype correlations for autism, PWS, AS, and idic(15) syndrome.


The More or the Better? How Sex Contributes to Life Satisfaction.
Much cross-sectional research documented associations between sexuality and life satisfaction, but very little longitudinal research on the topic has considered whether changes in sexuality and life satisfaction unfold together over time. Using data from 5582 individuals in partnerships surveyed across 5786 intimate relationships (providing 18,712 observations for analysis) during five waves of the German Family Panel (pairfam), this study examined whether intraindividual changes in sexual frequency and satisfaction were associated with corresponding intraindividual changes in life satisfaction. Fixed effects regression modeling results showed that individuals reported a greater increase (decrease) in life satisfaction when they also experienced a more substantial increase (decrease) in sexual frequency and satisfaction. This finding was consistent for men and women. This study contributes to the literature by documenting that naturally occurring increases in sexual frequency and satisfaction over time predicted corresponding increases in life satisfaction.


Nilvadipine antagonizes both Abeta vasoactivity in isolated arteries, and the reduced cerebral blood flow in APPsw transgenic mice.
The development of Alzheimer's disease (AD) is generally thought to correlate with cerebral accumulation of Abeta. It has previously been shown that Abeta peptides enhance vasoconstriction in isolated arteries and oppose certain vasorelaxants. Moreover, exogenous application of Abeta peptides causes cerebral vasoconstriction in rodents and in transgenic mouse models of AD that overexpress Abeta there is reduced cerebral blood flow. In the present study, we investigated the effect of nilvadipine, a dihydropyridine-type calcium channel blocker, on Abeta induced vasoconstriction in isolated arteries and in vivo on cerebral blood flow (CBF) of an AD transgenic mouse model overexpressing Abeta (Tg APPsw line 2576). Nilvadipine completely inhibited the vasoactivity elicited by Abeta in rat aortae and in human middle cerebral arteries. The effect of a short treatment duration (2 weeks) with nilvadipine on regional CBF was investigated in 13-month-old Tg APPsw mice and control littermates using a laser Doppler imager. Additionally, CBF was also measured in 20-month-old Tg APPsw mice and control littermates that were chronically treated with nilvadipine for 7 months. Untreated Tg APPsw mice showed a reduction of regional CBF compared to their untreated control littermates. Nilvadipine restored cortical perfusion levels in Tg APPsw to values similar to those observed in control littermates without notably affecting the CBF of control mice. All together, these data suggest that nilvadipine might be useful for the treatment of oligemia associated with AD.


Brucella Periplasmic Protein EipB Is a Molecular Determinant of Cell Envelope Integrity and Virulence.
The Gram-negative cell envelope is a remarkable structure with core components that include an inner membrane, an outer membrane, and a peptidoglycan layer in the periplasmic space between. Multiple molecular systems function to maintain integrity of this essential barrier between the interior of the cell and its surrounding environment. We show that a conserved DUF1849 family protein, EipB, is secreted to the periplasmic space of Brucella species, a monophyletic group of intracellular pathogens. In the periplasm, EipB folds into an unusual 14-stranded β-spiral structure that resembles the LolA and LolB lipoprotein delivery system, though the overall fold of EipB is distinct from LolA/LolB. Deletion of eipB results in defects in Brucella cell envelope integrity in vitro and in maintenance of spleen colonization in a mouse model of Brucella abortus infection. Transposon disruption of ttpA, which encodes a periplasmic protein containing tetratricopeptide repeats, is synthetically lethal with eipB deletion. ttpA is a reported virulence determinant in Brucella, and our studies of ttpA deletion and overexpression strains provide evidence that this gene also contributes to cell envelope function. We conclude that eipB and ttpA function in the Brucella periplasmic space to maintain cell envelope integrity, which facilitates survival in a mammalian host.IMPORTANCEBrucella species cause brucellosis, a global zoonosis. A gene encoding a conserved DUF1849-family protein, which we have named EipB, is present in all sequenced Brucella and several other genera in the class Alphaproteobacteria The manuscript provides the first functional and structural characterization of a DUF1849 protein. We show that EipB is secreted to the periplasm where it forms a spiral-shaped antiparallel β protein that is a determinant of cell envelope integrity in vitro and virulence in an animal model of disease. eipB genetically interacts with ttpA, which also encodes a periplasmic protein. We propose that EipB and TtpA function as part of a system required for cell envelope homeostasis in select Alphaproteobacteria.


[Intra-arterial occlusion of renal arteriovenous fistula using a detachable balloon].
Several intra-arterial embolization techniques with polimerization substances, particles, thrombogenic coils and silicone and latex balloons have been used in the endovascular therapy of arteriovenous fistulas in different vascular territories. Using the Seldinger technique by femural route and with a coaxial system including a microcatheter with a latex Debrun type balloon, the authors describe the selective occlusion of an iatrogenic arteriovenous fistula of the left kidney.


Long term and frequent electrophysiological observation in carpal tunnel syndrome.
Carpal tunnel syndrome (CTS) is one of the most common compression neuropathies in neurology. Electromyography (EMG) including nerve conduction study (NCS) is the most useful diagnostic technique for CTS. In this study, we aim to demonstrate changes in electrophysiological parameters in different level of CTS patients by frequent EMG studies. We prospectively followed patients with CTS regularly once every 12 weeks for 1 year. Fourteen women (28 hands) with EMG/NCS findings of CTS were observed and classified in 3 groups according to electrophysiological severity. All patients were instructed to wear the splint for 12 weeks. At the end of this period, patients were evaluated by electrophysiologic parameters. If findings were still abnormal, they were encouraged to continue wearing the splint. In severe cases, surgical release was carried out. No statistically significant changes were noted in EMG recordings of mild cases repeated every 3 months. It was determined that significant improvements begin to occur in the moderate group in all parameters, except for the amplitude of the median sensory nerve. However, when the mean values were studied in the severe CTS group, it was observed that the preoperative motor and sensory parameters became increasingly impaired, but approached the initial values in the first evaluation in the postoperative period. Subjects with CTS, particularly moderate as determined by electrophysiology, may benefit from conservative therapy, with improvements which continue for about one year. In severe cases the main treatment modality seems to be operation. Frequent electrophysiological follow-ups may be useful in guiding treatment.


Chronic lymphocytic leukemia is associated with decreased survival of patients with malignant melanoma and Merkel cell carcinoma in a SEER population-based study.
To delineate outcomes of malignant melanoma (MM) and Merkel cell carcinoma (MCC) in patients with chronic lymphocytic leukemia (CLL) or non-Hodgkin's lymphoma (NHL). We identified patients with MM or MCC reported to the Surveillance, Epidemiology, and End Results program and analyzed the effects of history of CLL/NHL on overall (OS) and cause-specific survival after MM or MCC. Expected survival was derived from patients with MM or MCC without CLL/NHL. From 1990 to 2006, 212,245 patients with MM and 3,613 patients with MCC were identified, of whom 1,246 with MM and 90 with MCC had a prior diagnosis of CLL/NHL. Patients with MM and a history of CLL/NHL had worse-than-expected OS as measured by standardized mortality ratio (SMR; SMR for CLL, 2.6; 95% CI, 2.3 to 3.0; SMR for NHL, 2.3; 95% CI, 2.1 to 2.6). MM cause-specific survival was worse than expected for patients with a history of CLL (SMR, 2.8; 95% CI, 2.2 to 3.4) or NHL (SMR, 2.1; 95% CI, 1.7 to 2.6). Among patients with MCC, OS was worse than expected for those with a history of CLL (SMR, 3.1; 95% CI, 2.2 to 4.3) or NHL (SMR, 1.9; 95% CI, 1.3 to 2.8). MCC cause-specific survival was worse than expected for patients with a history of CLL (SMR, 3.8; 95% CI, 2.5 to 5.9), but no difference was observed for NHL (SMR, 0.9; 95% CI, 0.4 to 2.1). Patients with CLL before diagnosis of MM or MCC have significantly worse OS and MM or MCC cause-specific survival than those without a history of CLL/NHL.


CXCR4 or CCR5 tropism of human immunodeficiency virus type 1 isolates does not determine the immunological milieu in patients responding to antiretroviral therapy.
Here we address whether CCR5 or CXCR4 tropism of the predominant viral strain detected before or on combination antiretroviral therapy (ART) explains why some human immunodeficiency virus (HIV)-infected patients who begin ART with advanced HIV disease retain low interferon (IFN)-gamma responses, despite recovery of CD4(+) T cell counts. Tropism was determined by culture and confirmed by gp120 V3 loop sequence of multiple plasma samples in eight adult male patients who began treatment with <50 CD4(+) T cells/microL. Four patients had mixed infections, one had only R5 HIV, and three had only X4 HIV. Of these, two carried CCR5Delta32. Viral tropism was not related to CD4(+) T cell counts or HIV RNA levels. When immunological responses were monitored over several years, IFN-gamma responses to cytomegalovirus were below the median value of uninfected controls and similar in patients with R5, X4, or mixed infection. Interleukin-5 responses were low and plasma soluble CD30 levels were high at treatment onset, but resolved with control of HIV replication irrespective of HIV tropism. Levels of LAG-3 (lymphocyte activation gene-3 protein) were elevated in patients with uncontrolled HIV replication. Hence the immunological milieu did not reflect HIV tropism.


Patch formation driven by stochastic effects of interaction between viruses and defective interfering particles.
Defective interfering particles (DIPs) are virus-like particles that occur naturally during virus infections. These particles are defective, lacking essential genetic materials for replication, but they can interact with the wild-type virus and potentially be used as therapeutic agents. However, the effect of DIPs on infection spread is still unclear due to complicated stochastic effects and nonlinear spatial dynamics. In this work, we develop a model with a new hybrid method to study the spatial-temporal dynamics of viruses and DIPs co-infections within hosts. We present two different scenarios of virus production and compare the results from deterministic and stochastic models to demonstrate how the stochastic effect is involved in the spatial dynamics of virus transmission. We compare the spread features of the virus in simulations and experiments, including the formation and the speed of virus spread and the emergence of stochastic patchy patterns of virus distribution. Our simulations simultaneously capture observed spatial spread features in the experimental data, including the spread rate of the virus and its patchiness. The results demonstrate that DIPs can slow down the growth of virus particles and make the spread of the virus more patchy.


Review-Recent Advances in FSCV Detection of Neurochemicals via Waveform and Carbon Microelectrode Modification.
Fast scan cyclic voltammetry (FSCV) is an analytical technique that was first developed over 30 years ago. Since then, it has been extensively used to detect dopamine using carbon fiber microelectrodes (CFMEs). More recently, electrode modifications and waveform refinement have enabled the detection of a wider variety of neurochemicals including nucleosides such as adenosine and guanosine, neurotransmitter metabolites of dopamine, and neuropeptides such as enkephalin. These alterations have facilitated the selectivity of certain biomolecules over others to enhance the measurement of the analyte of interest while excluding interferants. In this review, we detail these modifications and how specializing CFME sensors allows neuro-analytical researchers to develop tools to understand the neurochemistry of the brain in disease states and provide groundwork for translational work in clinical settings.


Storage Conditions and Microbial Quality of Smoked Dry Herring in Ghana.
A microbial profile of smoked dry herring stored under various storage conditions for up to 6 months at ambient temperature was determined. The fish were stored in polyethylene bags, polyethylene bags with desiccant, the traditional oven storage, modified storage structure, and freezer (control) storage. The fish stored in polyethylene bags with or without desiccant spoiled rapidly. Microbial counts were also very high. The microbial counts of fish stored in the traditional oven and the modified structure were small, even less than that stored in freezer. The storage losses were only 4% for the modified structure while the traditional oven storage was 29%. The major pathogenic bacterium found in smoked dry herring was Staphylococcus aureus .


Epidemiological and clinical features of invasive pneumococcal disease caused by serotype 12F in adults, Japan.
Enhanced surveillance of invasive pneumococcal disease (IPD) in adults was conducted during April 2013-March 2018 in 10 of 47 prefectures in Japan, and a total of 1277 IPD patients were enrolled. An emergence of IPD caused by serotype 12F was identified during May 2015-March 2018 through this surveillance. 12F isolates were composed of four related sequence types. In total, 120 patients with 12F IPD were reported during this period. To characterize the clinical features of 12F IPD, the disease characteristics of these patients were compared with those of 1157 patients with non-12F IPD. Compared with the non-12F IPD patients, a significantly lower proportion of 12F IPD patients was aged 65 years or older (55% vs. 70%), vaccinated with 23-valent pneumococcal polysaccharide (4% vs. 14%), had comorbid illness (65% vs. 77%), or were immunocompromised (19% vs. 30%; all P < 0.05). No significant difference in the proportion of case fatalities was found between the two groups. The proportions of those aged 65 years or older (53% vs. 69%) and with bacteremic pneumonia (35% vs. 69%) were significantly lower in 17 patients who died from 12F IPD than in 205 patients who died from non-12F IPD (all P < 0.05). Differences in clinical features were similarly found between 12F IPD patients and patients in low- or intermediate-level invasive potential serogroups. Our data demonstrated that serotype 12F was associated with IPD in younger adults and a lower proportion of comorbid illness, including immunocompromised conditions, in adult IPD, suggesting the high invasive potential of the serotype 12F. In addition, patients who died from 12F IPD were younger and had proportionately more bacteremia without focus. These findings may provide new insight into the pathogenesis of IPD in adults caused by 12F serotype with a high invasive potential.


Confirmatory bias in health decisions: Evidence from the MMR-autism controversy.
Since Wakefield et al. (1998), the public was exposed to mixed information surrounding the claim that measles-mumps-rubella vaccine causes autism. A persistent trend to delay the vaccination during 1998-2011 in the US was driven by children of college-educated mothers, suggesting that these mothers held biases against the vaccine influenced by the early unfounded claim. Consistent with confirmatory bias, exposures to negative information about the vaccine strengthened their biases more than exposures to positive information attenuated them. Positive online information, however, had strong impacts on vaccination decisions, suggesting that online dissemination of vaccine-safety information may help tackle the sticky misinformation.


Thiamine leads to oxidative stress resistance via regulation of the glucose metabolism.
Thiamine diphosphate (ThDP) is an essential cofactor for important enzymes in carbohydrate, amino acid and lipid metabolisms. It is also known that thiamine plays an important role in stress response of some organisms. In this study, we focused on the effect of thiamine on stress responses triggered by various stress agents. For this purpose, firstly, viability of Schizosaccharomyces pombe cell cultures was examined under oxidative, osmotic and heat stresses. The highest tolerance observed in cell viability due to the presence of extracellular thiamine (1.5 µM) was found only against oxidative stress. Then, enzyme activity of catalase and superoxide dismutase (SOD) involved in antioxidant defense mechanism and the expression analysis of genes encoding enzymes related to glucose metabolism and stress response pathways were investigated under oxidative stress. In this condition, it was not observed any difference in SOD and catalase activities, and their gene expressions due to the presence of thiamine, whereas the upregulation of pyruvate dehydrogenase (pdb1), transketolase (SPBC2G5.05), fructose-1,6-bis-phosphatase (fbp1) and the downregulation of pyruvate decarboxylase (pdc201) were observed. In conclusion, these findings suggest that extracellular thiamine leading to oxidative stress resistance have an impact on the regulation of glucose metabolism by shifting the energy generation from fermentation to respiration.


Relationship between cold hardiness and supercooling point in Aedes albopictus eggs.
For many insects, low temperatures are not lethal unless their tissues freeze. To determine whether freezing is the cause of low temperature mortality of Aedes albopictus eggs, we measured their lower lethal temperature, the temperature that causes 50% mortality in a population, and supercooling point, the temperature at which the tissues freeze. Tropical and temperate Ae. albopictus eggs were tested under different diapause and cold acclimation conditions. Temperate Ae. albopictus eggs had a lower lethal temperature than tropical Ae. albopictus eggs. Diapause and cold acclimation decreased the lower lethal temperatures of temperate eggs. However, neither diapause, cold acclimation, nor geographic origin affected Ae. albopictus egg supercooling points. All lower lethal temperatures were above -13 degrees C and all supercooling points were below -26 degrees C, indicating prefreeze mortality. Eggs of Aedes triseriatus and Aedes aegypti also died before they froze.


Circulating levels of secretory- and lipoprotein-associated phospholipase A2 activities: relation to atherosclerotic plaques and future all-cause mortality.
Secretory- and lipoprotein-associated phospholipases A2 (sPLA2 and Lp-PLA2) are enzymes both suggested to be of importance for atherosclerosis. We investigated relationships between the activities of these enzymes in the circulation and atherosclerosis as well as future clinical events. The population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study included 1016 randomly selected subjects, all aged 70. The prevalence of carotid artery plaques was recorded by ultrasound (n= 954), and arterial stenosis was assessed by whole-body magnetic resonance angiography (WBMRA, n= 302). Secretory-associated phospholipase A2 [odds ratio 1.23 for 1 SD increase, 95% confidence interval (CI): 1.05-1.44, P= 0.007], but not Lp-PLA2 (P= 0.26), activity was significantly related to carotid atherosclerosis and to the amount of stenosis at WBMRA (P= 0.006) following adjustment for multiple risk factors (waist circumference, serum triglycerides, body mass index, C-reactive protein, high density lipoprotein-C, low density lipoprotein-C, triglycerides, GFR, fasting glucose, blood pressure, statin use, and exercise habits). Secretory-associated phospholipase A2 [hazard ratio (HR) 1.45 for 1 SD increase, 95% CI: 1.15-1.84, P= 0.001], but not Lp-PLA2 (HR 0.95, P= 0.55), activity was a significant risk factor for all-cause mortality (114 had died) during 7.0 years follow-up after adjustment for the risk factors described above. In a sample of 1029 post-myocardial infarction (MI) patients (French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction), sPLA2 (adjusted HR 1.32 for 1 unit increase, 95% CI: 1.02-1.71, P= 0.036), but not Lp-PLA2 (HR 1.03, P= 0.90), activity predicted death or recurrent MI during 1-year follow-up (n= 136 cases). sPLA2 activity was related to atherosclerosis and predicted all-cause mortality in a sample of elderly subjects, as well as death or MI in post-MI patients.


The influence and mechanism of ligustilide, senkyunolide I, and senkyunolide A on echinacoside transport through MDCK-MDR1 cells as blood-brain barrier in vitro model.
Efficient transcytosis across the blood-brain-barrier is an important strategy for accessing drug targets within the central nervous system. Ligusticum chuanxiong Hort. was used as a messenger drug to increase the distribution of drugs in brain tissue in Traditional Chinese Medicine. The present study investigates the transport of echinacoside (ECH) through MDCK-MDR1 cell and the effects of ligustilide (LIG), senkyunolide A (SENA) and senkyunolide I (SENI) in chuanxiong on its transport. The results indicated that the absorption of ECH was relatively poor in MDCK-MDR1cells, and was concentration dependent and not saturable. The P-glycoprotein inhibitor verapamil could significantly increase the transport of ECH. It indicated that the transport mechanism might be passive diffusion as the dominating process with the active transportation mediated mechanism involved. The increased apparent permeability of ECH in A → B direction by ethylenediaminetetraacetic acid-Na2 suggested that ECH was absorbed via the paracellular route. The transport of ECH in A → B direction significantly increased when co-administrated with increasing concentrations of LIG, SENI and SENA. Western blot analysis and a decrease in transepithelial electrical resistance during the permeation experiment indicated that LIG, SENI and SENA had enhanced the transport of ECH in the BBB models attribute to down-regulate the expressions of claudin-5 and zonula occludens-1 expression.


Divergent trends in the risk of spring frost damage to trees in Europe with recent warming.
Frost events during the active growth period of plants can cause extensive frost damage with tremendous economic losses and dramatic ecological consequences. A common assumption is that climate warming may bring along a reduction in the frequency and severity of frost damage to vegetation. On the other hand, it has been argued that rising temperature in late winter and early spring might trigger the so called "false spring", that is, early onset of growth that is followed by cold spells, resulting in increased frost damage. By combining daily gridded climate data and 1,489 k in situ phenological observations of 27 tree species from 5,565 phenological observation sites in Europe, we show here that temporal changes in the risk of spring frost damage with recent warming vary largely depending on the species and geographical locations. Species whose phenology was especially sensitive to climate warming tended to have increased risk of frost damage. Geographically, compared with continental areas, maritime and coastal areas in Europe were more exposed to increasing occurrence of frost and these late spring frosts were getting more severe in the maritime and coastal areas. Our results suggest that even though temperatures will be elevated in the future, some phenologically responsive species and many populations of a given species will paradoxically experience more frost damage in the future warming climate. More attention should be paid to the increased frost damage in responsive species and populations in maritime areas when developing strategies to mitigate the potential negative impacts of climate change on ecosystems in the near future.


Effect of in-patient cardiac rehabilitation at rehabilitation hospital for cardiology patients: two-center trial.
The effectiveness of cardiac rehabilitation (CR) in patients with cardiovascular disease requiring continuous CR from an acute care hospital to a convalescent rehabilitation hospital is unknown. Therefore, we compared the effect of CR in a rehabilitation hospital for patients with cardiovascular disease with that of those who underwent cardiovascular surgery. Sixty-nine consecutive patients were admitted to two rehabilitation hospitals for CR. Patients were classified by primary disease into two groups: patients with cardiovascular disease (cardiology group, 26 patients) and patients who underwent cardiovascular surgery (surgery group, 43 patients). Clinical information, physical function, cognitive function, activities of daily living (ADL), quality of life (QOL), amount of CR, and length of hospital stay were compared between the two groups. Compared with clinical features, age was significantly higher in the cardiology group (P < 0.001), and the preadmission Barthel index was significantly lower in the cardiology group (P = 0.025). Physical function at the time of transfer was significantly lower in the cardiology group than in the surgery group for the short physical performance battery (P < 0.001), gait speed (P = 0.005), and 6-min walking distance (P = 0.042). No significant difference was found in the amount of CR performed or the length of hospital stay, and no interaction effects were observed in improvements in physical function, exercise tolerance, or QOL. In conclusion, in rehabilitation hospitals, patients with cardiovascular disease were older, had lower preadmission ADL, and had lower a physical function at transfer than those who underwent cardiovascular surgery, but CR improved physical function and QOL to the same extent. The results suggest that the recovery of patients with cardiovascular disease may be similar to those who undergo cardiovascular surgery.


Isolation and Lack of Potential Mates may Threaten an Endangered Arid-Zone Acacia.
Clonality may provide reproductive assurance for many threatened plants while limiting sexual reproductive success either through energetic tradeoffs or because clones are self-incompatible. Most stands of the Australian arid-zone plant Acacia carneorum, flower annually but low seed set and an absence of sexual recruitment now suggest that this species and other, important arid-zone ecosystem engineers may have low genotypic diversity. Indeed, our recent landscape-scale genetic study revealed that stands are typically monoclonal, with genets usually separated by kilometers. An inability to set sexually produced seed or a lack of genetically diverse mates may explain almost system-wide reproductive failure. Here, using microsatellite markers, we genotyped 100 seeds from a rare fruiting stand (Middle-Camp), together with all adult plants within it and its 4 neighboring stands (up to 5 km distant). As expected, all stands surveyed were monoclonal. However, the Middle-Camp seeds were generated sexually. Comparing seed genotypes with the single Middle-Camp genotype and those of genets from neighboring and other regional stands (n = 26), revealed that 73 seeds were sired by the Middle-Camp genet. Within these Middle-Camp seeds we detected 19 genotypes in proportions consistent with self-fertilization of that genet. For the remaining 27 seeds, comprising 8 different genotypes, paternity was assigned to the nearest neighboring stands Mallee and Mallee-West, approximately 1 km distant. Ironically, given this species' vast geographic range, a small number of stands with reproductively compatible near neighbors may provide the only sources of novel genotypes.


Bone scintigraphy in uremic pulmonary calcification.
The value of Tc-99m HEDP bone scintigraphy as a means of detecting uremic pulmonary calcification was studied in 30 chronic dialysis patients. A high incidence of currently recognized predisposing factors for metastatic calcification was found and calcification was recorded at other sites. Scintigraphy was performed after reducing background activity by hemodialysis to levels found in normals. From chest images and chest-to-spine activity ratios, evidence of pulmonary calcification could be obtained in only one patient, and subsequent histologic examination revealed extensive calcification. High chest-to-spine activity ratios suggested increased pulmonary radionuclide uptake in several other patients, but these findings were not conclusive. These results indicate that uremic pulmonary calcification--which, according to autopsy studies, develops in about 60-75% of dialysis patients--cannot be detected with bone-seeking radiopharmaceuticals, unless the calcification is severe. This is probably due to the unusual crystalline and chemical composition of uremic pulmonary calcification.


LIGHT (TNFSF14) enhances osteogenesis of human bone marrow-derived mesenchymal stem cells.
Osteoporosis is a progressive systemic skeletal disease associated with decreased bone mineral density and deterioration of bone quality, and it affects millions of people worldwide. Currently, it is treated mainly using antiresorptive and osteoanabolic agents. However, these drugs have severe adverse effects. Cell replacement therapy using mesenchymal stem cells (MSCs) could serve as a treatment strategy for osteoporosis in the future. LIGHT (HVEM-L, TNFSF14, or CD258) is a member of the tumor necrosis factor superfamily. However, the effect of recombinant LIGHT (rhLIGHT) on osteogenesis in human bone marrow-derived MSCs (hBM-MSCs) is unknown. Therefore, we monitored the effects of LIGHT on osteogenesis of hBM-MSCs. Lymphotoxin-β receptor (LTβR), which is a LIGHT receptor, was constitutively expressed on the surface of hBM-MSCs. After rhLIGHT treatment, calcium and phosphate deposition in hBM-MSCs, stained by Alizarin red and von Kossa, respectively, significantly increased. We performed quantitative real-time polymerase chain reaction to examine the expressions of osteoprogenitor markers (RUNX2/CBFA1 and collagen I alpha 1) and osteoblast markers (alkaline phosphatase, osterix/Sp7, and osteocalcin) and immunoblotting to assess the underlying biological mechanisms following rhLIGHT treatment. We found that rhLIGHT treatment enhanced von Kossa- and Alizarin red-positive hBM-MSCs and induced the expression of diverse differentiation markers of osteogenesis in a dose-dependent manner. WNT/β-catenin pathway activation strongly mediated rhLIGHT-induced osteogenesis of hBM-MSCs, accelerating the differentiation of hBM-MSCs into osteocytes. In conclusion, the interaction between LIGHT and LTβR enhances osteogenesis of hBM-MSCs. Therefore, LIGHT might play an important role in stem cell therapy.


Repair by Src kinase of function-impaired RET with multiple endocrine neoplasia type 2A mutation with substitutions of tyrosines in the COOH-terminal kinase domain for phenylalanine.
An oncogenic mutant of c-RET as a receptor-type tyrosine kinase, termed RET-MEN2A, displays both cell-transforming activity in vivo and strong catalytic activity in vitro. In this study, we compared the activities of mutant RET-MEN2A with substitutions of each of nine tyrosines for phenylalanine (Y1062F, Y1015F, Y981F, Y952F, Y928F, Y905F, Y900F, Y864F, and Y826F), which had been transfected into NIH 3T3 cells. In RET-MEN2A with the Y905F mutation, the cell-transforming activity was drastically reduced with a great reduction in the in vitro catalytic activity. Unexpectedly, we found that in vitro kinase activity was severely impaired in RET-MEN2A with Y981F, Y952F, or Y928F mutation, which displayed near-normal cell-transforming activity and only a partially impaired tyrosine phosphorylation level in vivo. Phosphoamino acid analysis actually demonstrated some increase in phosphotyrosine in the Y905F mutant but no or barely detectable increase in the Y981F, Y952F, or Y928F mutant after incubation for in vitro kinase assay. This suggested a crucial role of the Y981/Y952/Y928-linked structural integrity of the COOH end of the catalytic domain of RET in starting Y905 autophosphorylation. Interestingly, the apparent defect in intrinsic kinase activity in vitro in the Y981F, Y952F, or Y928F mutant, but not the reduction in activity in the Y905F mutant, could be partially repaired or restored by c-Src or, more extensively, by v-Src, which promoted Y905 phosphorylation in trans. A complex was shown to be formed between v-Src and RET-MEN2A through association of both with a cholesterol-rich membrane microdomain known as "a raft," possibly for efficient contact of submembranous domains of Src and RET to promote phosphorylation of Y905 of the latter. Finally, endogenous c-Src was shown to promote Y905 phosphorylation of the Y981F mutant in vivo. These results reveal a novel Src kinase-mediated repair mechanism of otherwise function-impaired mutant RET kinases.


The cost-effectiveness of azithromycin in reducing exacerbations in uncontrolled asthma.
Add-on azithromycin (AZM) results in a significant reduction in exacerbations among adults with persistent uncontrolled asthma. The aim of this study was to assess the cost-effectiveness of add-on AZM in terms of healthcare and societal costs.The AMAZES trial randomly assigned 420 participants to AZM or placebo. Healthcare use and asthma exacerbations were measured during the treatment period. Healthcare use included all prescribed medicine and healthcare contacts. Costs of antimicrobial resistance (AMR) were estimated based on overall consumption and published estimates of costs. The value of an avoided exacerbation was based on published references. Differences in cost between the two groups were related to differences in exacerbations in a series of net monetary benefit estimates. Societal costs included lost productivity, over the counter medicines, steroid induced morbidity and AMR costs.Add-on AZM resulted in a reduction in healthcare costs (mean (95% CI)) including nights in hospital (AUD 433.70 (AUD 48.59-818.81) or EUR 260.22 (EUR 29.15-491.29)), unplanned healthcare visits (AUD 20.25 (AUD 5.23-35.27) or EUR 12.15 (EUR 3.14-21.16)), antibiotic costs (AUD 14.88 (AUD 7.55-22.21) or EUR 8.93 (EUR 4.53-13.33)) and oral corticosteroid costs (AUD 4.73 (AUD 0.82-8.64) or EUR 2.84 (EUR 0.49-5.18)); all p<0.05. Overall healthcare and societal costs were lower (AUD 77.30 (EUR 46.38) and AUD 256.22 (EUR 153.73) respectively) albeit not statistically significant. The net monetary benefit of add-on AZM was estimated to be AUD 2072.30 (95% CI AUD 1348.55-2805.23) or (EUR 1243.38 (EUR 809.13-1683.14) assuming a willingness to pay per exacerbation avoided of AUD 2651 (EUR 1590.60). Irrespective of the sensitivity analysis applied, the net monetary benefit for total, moderate and severe exacerbations remained positive and significant.Add-on AZM therapy in poorly controlled asthma was a cost-effective therapy. Costs associated with AMR did not influence estimated cost-effectiveness.


Response of the nine-banded armadillo (Dasypus novemcinctus) to gonadotropins and steroids.
Adult male and female, nine-banded armadillos (Dasypus novemcinctus) were treated with exogenous gonadotropins and steroids to induce mating in captivity. Gonadotropin treatment induced follicular development and ovulation in the female but failed to enhance semen quality in the male. The number of ovarian follicles increased as the dosage of pregnant mare serum gonadotropin increased; ovulation rate appeared to be inversely related to dose. Mating behavior was not detected in any of the trials, but a pattern of cyclic cytological changes in urogenital smears, which could be used to detect the follicular phase of the estrous cycle, was observed. The modal duration of the estrous cycle was found to be 4 days.


How many problems do family physicians manage at each encounter? A WReN study.
The number of problems managed concurrently by family physicians during patient encounters has not been fully explored despite the implications for quality assessment, guideline implementation, education, research, administration, and funding. Our study objective was to determine the number of problems physicians report managing at each visit and compare that with the number reflected in the chart and the bill. Twenty-nine members of the Wisconsin Research Network reported on encounters with 572 patients using a physician problem log. The patient chart notes and the diagnoses submitted for billing from the encounters were compared with the information in these logs. The physicians reported managing an average of 3.05 problems per encounter and recorded 2.82 in the chart and 1.97 on the bill. For all patients, 37% of encounters addressed more than 3 problems, and 18% addressed more than 4. For patients older than 65 years, there was an average of 3.88 problems at each visit, and for diabetic patients there was an average of 4.60. There was evidence for the selective omission of mental health and substance problems from the diagnoses used for billing. Family medicine involves the concurrent care of multiple problems, which billing data do not adequately reflect. Our findings suggest a mismatch between family medicine and current approaches to quality assessment, guideline implementation, education, research, administration, and funding. Activities in all these areas need to address the physician's task of prioritizing and integrating care for multiple problems concurrently.


Fatty acids in animals: thrombosis and hemostasis.
Long-chain fatty acids, including stearic acid, can cause thrombosis when they are injected into the systemic circulation of animals. The toxicity is decreased if the fatty acids are bound to albumin. To date, the effect of individual fatty acid feeding is not known. In general, feeding animals diets high in saturated fat followed by the injection of a thrombogenic stimulus is associated with a greater incidence of thrombosis than when a normal diet or a diet high in unsaturated or polyunsaturated fat is fed. A high dietary intake of long-chain polyunsaturated fatty acids of the n-3 family may prevent thrombosis in animals. In assessing the effects of dietary fatty acids, the ability of the organism, be it animal or human, to convert fatty acids to less thrombogenic fatty acids (stearic to oleic) or create an antithrombotic fatty acid (linolenic to eicosapentaenoic) is a major attribute. Further studies should consider the storage of fatty acids in tissues and their release into the blood and the potential impairment of albumin binding and fatty acid transport mechanisms.


Genome-wide profiling of responses to cadmium in the diatom Phaeodactylum tricornutum.
The only group of organisms in which a biological function for cadmium has been shown is the diatoms, which are unicellular phytoplankton. Yet diatoms exhibit similar sensitivity to Cd as other groups of phytoplankton. We have investigated responses of Cd on molecular, metabolic, and physiological levels in the diatom Phaeodactylum tricornutum. P. tricornutum apparently has a high tolerance to Cd; only minor responses were observed on growth, pigment, and transcriptional changes at cadmium concentrations of 123 μg/L. No significant changes in chlorophyll and xanthophyll levels were observed, and the very few transcripts affected strongly indicate that the cells were able to respond to the increased Cd(2+) levels without changing proteins levels. At 10 times this concentration, 1230 μg/L, a much clearer response was observed, including transcripts encoding proteins involved in metal transport, cell signaling, and detoxification processes. Our results point toward putative pathways for the removal or detoxification of Cd and its metabolites as well as a possible Cd uptake mechanism. We predict that ATPase5-1B is involved in removal of Cd by pumping Cd(2+) ions out of the cell, whereas VIT1/CCC1 sequesters Cd(2+) in the vacuole.


[Use of an immunoenzyme method on a solid-phase carrier for determining the tularemia antigen].
The method of the highly sensitive (up to 10 ng/ml) and specific determination of soluble tularemia antigen, based on the use of "sandwich" type ELISA techniques, has been developed. The dependence of the specificity and sensitivity of the method on the degree of purification of antibodies and their peroxidase conjugates used in the assay has been studied. The study has revealed that the best results can be obtained with the use of purified IgG and its conjugate free of unbound peroxidase. Both foreign peroxidase preparations and type A enzyme manufactured in the USSR can be equally used as enzymatic labels.


How many hindsight biases are there?
The answer is three: questioning a conceptual default assumption in hindsight bias research, we argue that the hindsight bias is not a unitary phenomenon but consists of three separable and partially independent subphenomena or components, namely, memory distortions, impressions of foreseeability and impressions of necessity. Following a detailed conceptual analysis including a systematic survey of hindsight characterizations in the published literature, we investigated these hindsight components in the context of political elections. We present evidence from three empirical studies that impressions of foreseeability and memory distortions (1) show hindsight effects that typically differ in magnitude and sometimes even in direction, (2) are essentially uncorrelated, and (3) are differentially influenced by extraneous variables. A fourth study found similar dissociations between memory distortions and impressions of necessity. All four studies thus provide support for a separate components view of the hindsight bias. An important consequence of such a view is that apparent contradictions in research findings as well as in theoretical explanations (e.g., cognitive vs. social-motivational) might be alleviated by taking differences between components into account. We also suggest conditions under which the components diverge or converge.


Remote cerebellar hemorrhage as a complication of lumbar spine surgery.
Remote cerebellar hemorrhage (RCH) is a rare yet potentially fatal complication of supratentorial and spinal surgery, where there has been either intentional or accidental breach of the dura. We present a case of RCH following a L4-5 decompression laminectomy complicated by an intraoperative dural tear which was detected and repaired at the time of surgery. Despite prompt intra-operative repair of the dura, there was persistent cerebrospinal fluid leak as evidenced by a high subfascial epidural drain output which resulted in bilateral intraparenchymal cerebellar hemorrhage. The patient was managed conservatively and recovered without neurological deficits.


Sacral nerve stimulation for faecal incontinence in patients with previous partial spinal injury including disc prolapse.
This study examined the use of sacral nerve stimulation (SNS) to treat faecal incontinence in patients with partial spinal injury. Patients selected for SNS had experienced more than one episode of faecal incontinence per week to liquid or solid stool for more than 1 year and had failed maximal conservative treatment. All patients had an intact external anal sphincter. Temporary SNS was performed in 13 patients (median age 58.5 (range 39-73) years). The spinal insults were disc prolapse (six), trauma (four), spinal stenosis (one) or occurred during neurosurgery (two). Twelve patients (eight women and four men) had successful temporary stimulation and proceeded to permanent implantation. The median follow-up time was 12 (range 6-24) months. The mean(s.d.) number of episodes of incontinence decreased from 9.33(7.64) per week at baseline to 2.39(3.69) at last follow-up (P = 0.012). The number of days per week with incontinence and staining decreased significantly (both P < 0.001). Ability to defer defaecation improved from a median of not being able to defer (range 0-1 min) to being able to defer for 5-15 (range 0 to over 15) min (P = 0.022). SNS can benefit patients with faecal incontinence following partial spinal injury.


Depth of delayed cooling alters neuroprotection pattern after hypoxia-ischemia.
Hypothermia after perinatal hypoxia-ischemia (HI) is neuroprotective; the precise brain temperature that provides optimal protection is unknown. To assess the pattern of brain injury with 3 different rectal temperatures, we randomized 42 newborn piglets: (Group i) sham-normothermia (38.5-39 degrees C); (Group ii) sham-33 degrees C; (Group iii) HI-normothermia; (Group iv) HI-35 degrees C; and (Group v) HI-33 degrees C. Groups iii through v were subjected to transient HI insult. Groups ii, iv, and v were cooled to their target rectal temperatures between 2 and 26 hours after resuscitation. Experiments were terminated at 48 hours. Compared with normothermia, hypothermia at 35 degrees C led to 25 and 39% increases in neuronal viability in cortical gray matter (GM) and deep GM, respectively (both p < 0.05); hypothermia at 33 degrees C resulted in a 55% increase in neuronal viability in cortical GM (p < 0.01) but no significant increase in neuronal viability in deep GM. Comparing hypothermia at 35 and 33 degrees C, 35 degrees C resulted in more viable neurons in deep GM, whereas 33 degrees C resulted in more viable neurons in cortical GM (both p < 0.05). These results suggest that optimal neuroprotection by delayed hypothermia may occur at different temperatures in the cortical and deep GM. To obtain maximum benefit, you may need to design patient-specific hypothermia protocols by combining systemic and selective cooling.


Osteogenesis and cytotoxicity of a new Carbon Fiber/Flax/Epoxy composite material for bone fracture plate applications.
This study is part of an ongoing program to develop a new CF/Flax/Epoxy bone fracture plate to be used in orthopedic trauma applications. The purpose was to determine this new plate's in-vitro effects on the level of bone formation genes, as well as cell viability in comparison with a medical grade metal (i.e. stainless steel) commonly employed for fabrication of bone plates (positive control). Cytotoxicity and osteogenesis induced by wear debris of the material were assessed using Methyl Tetrazolium (MTT) assay and reverse transcription polymerase chain reaction (RT-PCR) for 3 osteogenesis specific gene markers, including bone morphogenetic proteins (BMP2), runt-related transcription factor 2 (Runx2) and Osterix. Moreover, the Flax/Epoxy and CF/Epoxy composites were examined separately for their wettability properties by water absorption and contact angle (CA) tests using the sessile drop technique. The MTT results for indirect and direct assays indicated that the CF/Flax/Epoxy composite material showed comparable cell viability with no cytotoxicity at all incubation times to that of the metal group (p≥0.05). Osteogenesis test results showed that the expression level of Runx2 marker induced by CF/Flax/Epoxy were significantly higher than those induced by metal after 48 h (p=0.57). Also, the Flax/Epoxy composite revealed a hydrophilic character (CA=68.07°±2.05°) and absorbed more water up to 17.2% compared to CF/Epoxy, which reached 1.25% due to its hydrophobic character (CA=93.22°±1.95°) (p<0.001). Therefore, the new CF/Flax/Epoxy may be a potential candidate for medical applications as a bone fracture plate, as it showed similar cell viability with no negative effect on gene expression levels responsible for bone formation compared to medical grade stainless steel.


Insomnia in Relation to Academic Performance, Self-Reported Health, Physical Activity, and Substance Use Among Adolescents.
Insomnia affects up to one in four adolescents and has been shown to have a negative impact on their mental and physical health. This study aimed to investigate the association between insomnia, academic performance, self-reported health, physical activity, school start time, and substance use among adolescents. A survey with a cross-sectional design was completed by adolescents (15-17 years old; n = 1504) in southern Sweden. The Minimal Insomnia Symptoms Scale (MISS) was used to operationalize insomnia. A multiple logistic regression analysis was used to analyze the relationship between insomnia and self-reported health, failed school courses, substance use, school start time, family financial situation, screen time, and gender. Insomnia (MISS ≥ 6) was associated with poor self-reported health (OR: 4.35), failed school courses (OR: 1.47), and use of alcohol and/or cigarettes (OR: 1.43). When the combined effect of self-reported health and physical activity were investigated, a combination of low physical activity (≤1 time/week) and poor self-reported health was strongly associated with insomnia (OR: 18.87). Insomnia was associated with other problems that in themselves are risk factors for poor health. This highlights the need for a holistic health-promoting approach to prevent insomnia, such as efforts to promote physical activity, school success, and the reduction of alcohol/cigarette use.


Studies on endemic pneumonia of the albino rat. IV. Development of a rat colony free from respiratory infections.
A colony of albino rats was developed from three breeders (not germ-free) originally delivered by Cesarian section and artificially reared in the laboratories of Professor James A Reyniers. The colony has been maintained under quarantine since June, 1948, in the absence of any demonstrable involvement of the respiratory tract or of the middle ears. At autopsy pleuropneumonia-like organisms, Streptobacillus moniliformis, and the virus-like agent associated with endemic pneumonia were not recoverable from the lungs or the nasal passages of 81 young and adult rats. During the same time interval the morbidity rate of pneumonia in another rat colony known to be free from infectious catarrh was 51 per cent while the incidence of infection with the virus-like agent approached 100 per cent.


Comparison of osseointegration between laser-etched and magnesium-incorporated oxidized implants in the rabbit femur.
To compare the osseointegration of a laser-etched (LE) implant with a magnesium-incorporated oxidized (MgO) implant, evaluating their ability to enhance the bond strength between a titanium substrate and rabbit femur. Two type of dental implants, LE (test, commercially pure [CP] titanium grade 4) and MgO (control, CP titanium grade 4) (length, 8 mm; diameter, 3.3 mm), were evaluated for the surface characteristics using a field emission scanning electron microscope (FE-SEM), an energy dispersive spectrometer (EDS), and an optical three-dimensional profiling system. After that, two types of dental implants were implanted at the right and left distal femoral metaphysis of 10 adult rabbits weighing approximately 3.0 kg. After 6 weeks, histomorphometric analysis, removal torque tests, and surface analysis of the torque-tested implants were performed. After surgery, the LE group showed thick bonelike materials within the pores observed using FE-SEM (magnifications ×500 and ×900). The mean removal torque was 40.72 ± 13.3 Ncm for the test (LE) implant and 22.26 ± 6.4 Ncm for the control (MgO) implant, respectively (P = .041). The mean bone-implant contact in the three best consecutive threads in the cortical region was 63.35% ± 16.44% in the LE group and 51.63% ± 5.09% in the MgO. In the beginning stage of cancellous bone healing, biomechanical properties of the LE implant could influence a more favorable bone response than that of MgO.


Gender-Specific Association Between FGFR4 Gly388Arg Gene Variants and Hypertension.
Variations in fibroblast growth factor (FGF) levels have been associated with alterations in blood pressure. FGFs mediate their function through binding to their FGF receptor (FGFR). The FGFR4 Gly388Arg polymorphism is associated with cancer and cardiovascular diseases, but its association with hypertension is unclear. Here, we aimed to investigate the association between the FGFR4 Gly388Arg polymorphism and hypertension. Three hundred Saudi individuals (150 normotensive controls and 150 hypertensive subjects) were genotyped for the FGFR4 Gly388Arg (G/A) polymorphism using polymerase chain reaction-restriction fragment length polymorphism method. Anthropometrics, glucose and lipid profiles were measured for all subjects. The frequency of the FGFR4 Arg388 (A) allele was significantly higher in hypertensive subjects (36%) than controls (24.3%) (odds ratio [OR] 2.4, 95% confidence interval [CI] 1.5-3.83, p < 0.001). In addition, GA (OR 2.51, 95% CI 1.3-4.85, p = 0.006), AA (OR 5.58, 95% CI 1.79-11.8, p = 0.003), and GA + AA (OR 2.91, 95% CI 1.55-5.46, p = 0.001) genotypes were significantly associated with the risk of hypertension, even after adjusting for age, body mass index, and glucose. Gender stratification showed a significant association only in female subjects (p < 0.001). Furthermore, subjects with GA and AA genotypes showed significantly higher diastolic blood pressure than those with GG genotype (p = 0.004). The FGFR4 Arg388 allele is associated with an increased risk of hypertension in Saudi female subjects. The lack of association in men needs to be further investigated.


[Chronic Non Communicable Diseases and the support of intersectorial action to tackle them].
The study seeks to analyze the topic of Chronic Non Communicable Diseases (NCDs) and the role of intersectorial actions in tackling these diseases. It involved a narrative review through searches on Medline, Pubmed and Lilacs databases, and documents from the World Health Organization (WHO), the Pan American Health Organization (PAHO) and the Brazilian government. The link between the theme of intersectoriality and NCD is reviewed in the Global Conferences and Agendas on Health Promotion, and the role of other sectors in relation to effective interventions for NCDs. Some experiences of intersectorial activities for tackling NCDs are presented. The conclusion drawn is that the implementation of intersectorial action in conjunction with sectorial health policies in tackling NCDs has become a political priority, involving coordinated actions, negotiations forums, integrated planning and sustainable funding. It is necessary to seek the active participation of social actors in the advocacy, monitoring and accountability process, coupled with training processes for managers and other professionals, which will give sustainability to the social processes and required changes. Intersectorial partnerships are fundamental.


Non-partner sexual violence against women in Spain: lifetime prevalence, perpetrators and consequences on mental health.
Research on sexual violence by non-partners based on representative samples is scarce. The objectives of the study were (i) to analyse the prevalence of different forms of non-partner sexual violence in Spain and their perpetrators, (ii) to analyse the consequences of non-partner sexual violence on mental health and (iii) to estimate the percentage of rapes that are reported to the police. Data from the 2015 Spanish Survey on Violence against Women, a nationally representative sample of 10 171 women, were used. Three mutually exclusive categories of non-partner sexual violence were created to measure the effects of violence on health. Logistic regression models were fitted. The lifetime prevalence of non-partner sexual violence was 7.2%. All the categories of non-partner sexual violence were strongly associated with the different health outcomes. Rape increased the likelihood of reporting anxiety [odds ratio, OR: 3.77 (2.65-5.37)], sadness because of feelings of worthlessness [OR: 3.31 (2.32-4.73)] and the desire to cry without reason [OR: 3.46 (2.45-4.89)] more than 3-fold. The relationship of the victim with the perpetrator varied by the type of sexual victimization. Less than 6% of rapes were reported to the police in 2014. All forms of non-partner sexual violence, from unwanted sexual touching to rape, can lead to a multitude of mental health consequences. A public health approach to addressing this violence is needed.


[Intestinal parasitic diseases of school children in the Republic of Niger].
Coprologic surveys realized in schoolchildren in a few western areas of the Republic of Niger provided the following results. Concerning protozoa, the prevalence of amebiasis-infestation is strong in all the studies areas, giardiasis is more frequent in dry areas. As for the helminths, Hymenolepsis nana is met everywhere, the prevalence of ancylostomiasis decreases gradually from the south to the north and the endemic area of Schistosoma mansoni is limited to the extreme south of the country. The other helminthiasis are rare.


Lung tumorigenesis suppressing effects of a commercial kava extract and its selected compounds in A/J mice.
Lung cancer is the most deadly malignancy in the US. Chemoprevention is potentially a complementary approach to smoking cessation for lung cancer control. Recently, we reported that a commercially available form of kava extract significantly inhibits 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo(a)pyrene (BaP)-induced lung tumorigenesis in A/J mice at a dose of 10 mg per gram diet. In the present study, we examined the dose-dependent lung tumor inhibitory activities of kava and investigated potential active constituent(s). Mice treated with carcinogen alone contained 12.1±5.8 lung adenomas per mouse 22 weeks after final carcinogen administration. Mice that were fed diets containing kava at dosages of 1.25, 2.5, 5, and 10 mg/g of diet had 8.4±3.5, 6.6±3.5, 4.3±2.4, and 3.8±2.3 lung adenomas per mouse, respectively. This corresponds to a reduction of 31%, 46%, 65% and 69% in tumor multiplicity, which were all statistically significant (p < 0.05). Analyses of lung adenoma tissues derived from kava-treated animals revealed that kava significantly inhibited adenoma cell proliferation while it had no detectable effect on cell death, indicating that kava primarily suppressed lung tumorigenesis in A/J mice via inhibition of cell proliferation. Flavokawains A, B, and C, three chalcone-based components from kava, demonstrated greatly reduced chemopreventive efficacies even at concentrations much higher than their natural abundance, suggesting that they alone were unlikely to be responsible for kava's chemopreventive activity. Kava at all dosages and treatment regimens did not induce detectable adverse effects, particularly with respect to liver. Specifically, kava treatment showed no effect on liver integrity indicator enzymes or liver weight, indicating that kava may be potentially safe for long-term chemopreventive application.


Sociodemographic Pattern of Postmenopausal Women and Health Issues: A Study in Rural Bathinda, Punjab.
The diminishing hormonal concentrations in women after menopause may trap them into a number of reproductive health deficits. Their lifestyle, occupation, dietary constituents, etc., affect the overall health. Unfortunately, women belonging to rural areas lack basic amenities and cultural aspects give them a backseat to pay heed to personal health. Therefore, it is important to take into consideration the demographic profile of rural women. The objective of the study is to evaluate postmenopausal women of rural Punjab for sociodemographic, reproductive parameters and health issues. This study analyzed 425 women showing a high rate of illiteracy (74.6%), agricultural occupancy (85.2%), and consumption of vegetarian food (94.4%). The mean age at menarche and menopause was observed as 14.04 ± 1.12 and 47.97 ± 3.4 years, respectively. The most frequent complaints were fatigue (70.4%), backache (69.4), breathing problems (52.2%), and abdominal discomfort (43.1%). Later age at menopause in women was found concurrent with involvement in agriculture and exposure to pesticides. Delayed menopause may indicate a risk of reproductive cancers while protection in cardiovascular diseases. Therefore, age at menopause and dependent sociodemographic parameters should be considered important tools in determining the reproductive health of aging women. Large-scale studies dealing with this health aspect are warranted at village level.


The heart as an endocrine gland.
Two independent series of biomedical investigations have led to the discovery that the atria constitute a peptide-secreting endocrine gland. The first investigation is mainly morphological and started with the finding that mammalian atrial (but not ventricular) cardiocytes contain "dense bodies." These "dense bodies," later called "specific granules," were found to be different from lysosomes; to be made up of proteins; and to incorporate both 3H-leucine and 3H-fucose in a pattern typical of peptide-secreting endocrine cells. The finding that rat atrial granulation varied with the sodium and water balance led to the crucial observation that atrial extracts have natriuretic and diuretic effects. In less than five years, this new natriuretic hormone has been purified, sequenced and synthesized, and its CDNA and gene have been cloned. The atrial natriuretic factor (ANF) gene has been assigned to the distal short arm of chromosome 1 in band 1P36, while the mouse gene is localized in chromosome 4. The native and synthetic hormones exert identical wide ranging effects (possibly through particulate guanylate cyclase stimulation and adenylate cyclase inhibition) on the kidney, blood vessels, adrenal cortex, and pituitary. Physiopathologic implications of the hormone in experimental hypertension, congestive heart failure, and expansion of blood volume are already beginning to emerge. Concurrently, the search for the function of natriuretic hormones or factors (through studies of negative pressure breathing, atrial distension experiments, head-out water immersion, expansion of blood volume, Na+/K+-ATPase inhibition, and parabiosis experiments in Dahl rats) has provided a general framework within which to interpret this new cardiac function.


The impact of methoxypropylamino cyclohexenylidene ethoxyethylcyanoacetate (MCE) UVA1 filter on pigmentary and ageing signs: An outdoor prospective 8-week randomized, intra-individual comparative study in two populations of different genetic background.
Of all ultraviolet (UV) radiations reaching the earth, UVA1 rays have a higher potential of penetrating and producing clinically harmful consequences. While UV radiations up to 370 nm are well-blocked by current sunscreens, a photoprotection gap remains for the UVA1 wavelengths between 370 and 400 nm. This study was to assess under outdoor summer conditions the impact on pigmentation and skin ageing signs of a protection against UVA1 using methoxypropylamino cyclohexenylidene ethoxyethylcyanoacetate (MCE) filter added to a reference SPF50 sunscreen, in comparison with the same sunscreen without the MCE filter. This prospective randomized comparative intra-individual study was conducted in 113 women in Brazil and China. Subjects had their face and two forearms exposed twice-daily to a 1-h outdoor sunlight exposure over 8 weeks. Before exposure, the SPF50 sunscreen containing 3% MCE was applied on one half-face and one forearm and the same reference product without MCE on the other half-face and forearm. Primary study endpoint was skin colour changes (chromametry). Other endpoints included expert panel grading of pigmentation and facial skin ageing, and naïve panel assessment of facial skin radiance and homogeneity. After 8 weeks, the skin was darker on both forearms but the increase in sun-induced pigmentation was smaller with the SPF50/MCE sunscreen. Expert panel evaluations showed no change in severity scores for pigmentation and a decreased severity scores for facial skin ageing in areas protected with the SPF50/MCE product: severity scores in areas protected with the SPF50 alone were either increased (pigmentation) or unchanged (skin ageing). Naïve panel evaluations of skin radiance and homogeneity showed statistically significant superiority of the SPF50/MCE product. Overall, this study demonstrates that a protection with the SPF50/MCE sunscreen significantly reduces pigmentation and ageing signs compared to the same SPF50 sunscreen.


Circulating Dipeptidyl Peptidase Activity Is a Potential Biomarker for Inflammatory Bowel Disease.
Dipeptidyl peptidase (DPP)-4 is part of a larger family of proteases referred to as DPPs. DPP4 has been suggested as a possible biomarker for inflammatory bowel disease (IBD). Circulating DPP4 (cDPP4) enzyme activity was investigated as a potential biomarker for IBD. In addition, DPP enzyme activity and gene expression were quantified in colonic tissue of patients with IBD and non-IBD. In study 1, DPP enzyme activity was quantified in plasma samples from 220 patients with IBD (Crohn's disease [CD] n = 130 and ulcerative colitis [UC] n = 90) and non-IBD controls (n = 26) using a colorimetric assay. In study 2, tissue and plasma samples were collected from 26 patients with IBD and 20 non-IBD controls. Plasma C-reactive protein (CRP) was quantified in all patients. Colonic DPP4, DPP8, DPP9, and fibroblast activation protein (FAP) gene expression was determined by quantitative polymerase chain reaction. cDPP and cFAP enzyme activity was also measured. Sensitivity and specificity were determined by receiver operating characteristic curve analysis. In study 1, total cDPP activity was found to differentiate patients with CD with active disease (n = 18) from those in remission (n = 19; sensitivity 78% and specificity 63%). In study 2, total cDPP and cFAP activity was 28% and 48% lower in patients with elevated CRP (>10 mg/L), respectively, compared with patients with normal CRP. Gene expression of DPP4, FAP, and DPP8 was also significantly higher in colonic biopsies from patients with IBD compared with non-IBD patients (P < 0.05). Our findings implicate the DPP enzyme family in intestinal inflammation and suggest future biomarker applications to differentiate the pathophysiological aspects of IBD.


Size Estimation of Groups at High Risk of HIV/AIDS using Network Scale Up in Kerman, Iran.
To estimate the size of groups at high risk of HIV, Network Scale UP (NSU), an indirect method, was used. 500 Kermanian male aged 18 to 45 were recruited. 8 groups at high risk of HIV were defined: Users of opium, unknown drug, ecstasy, and alcohol; intra-venous drug users (IDUs; males who have extra-marital sex with females (MSF); male who have sex with female sex workers (MFSW); and male who have sex with other male (MSMs). We asked respondents whether they know anybody (probability method), and if yes, how many people (frequency method) in our target groups. Estimates derived in the probability method were higher than the frequency method. Based on the probability method, 13.7% (95% CI: 11.3%, 16.1%) of males used alcohol at least once in last year; the corresponding percent for opium was 13.1% (95% CI: 10.9%, 15.3%). In addition, 12% has extra-marital sex in last year (95% CI: 10%, 14%); while 7% (95% CI: 5.8%, 8.2%) had sex with a female sex worker. We showed that drug use is more common among young and mid-age males; although their sexual contacts were also considerable. These percentages show that special preventive program is needed to control an HIV transmission. Estimates derived from probability method were comparable with data from external sources. The underestimation in frequency method might be due to the fact that respondents are not aware of sensitive characteristics of all those in their network and underreporting is likely to occur.


Cluster Sets: Permitting Greater Mechanical Stress Without Decreasing Relative Velocity.
To determine the effects of intraset rest frequency and training load on muscle time under tension, external work, and external mechanical power output during back-squat protocols with similar changes in velocity. Twelve strength-trained men (26.0 ± 4.2 y, 83.1 ± 8.8 kg, 1.75 ± 0.06 m, 1.88:0.19 one-repetition-maximum [1RM] body mass) performed 3 sets of 12 back squats using 3 different set structures: traditional sets with 60% 1RM (TS), cluster sets of 4 with 75% 1RM (CS4), and cluster sets of 2 with 80% 1RM (CS2). Repeated-measures ANOVAs were used to determine differences in peak force (PF), mean force (MF), peak velocity (PV), mean velocity (MV), peak power (PP), mean power (MP), total work (TW), total time under tension (TUT), percentage mean velocity loss (%MVL), and percentage peak velocity loss (%PVL) between protocols. Compared with TS and CS4, CS2 resulted in greater MF, TW, and TUT in addition to less MV, PV, and MP. Similarly, CS4 resulted in greater MF, TW, and TUT in addition to less MV, PV, and MP than TS did. There were no differences between protocols for %MVL, %PVL, PF, or PP. These data show that the intraset rest provided in CS4 and CS2 allowed for greater external loads than with TS, increasing TW and TUT while resulting in similar PP and %VL. Therefore, cluster-set structures may function as an alternative method to traditional strength- or hypertrophy-oriented training by increasing training load without increasing %VL or decreasing PP.


Sedation, delirium and mechanical ventilation: the 'ABCDE' approach.
Delirium and ICU-acquired weakness are frequent in critically ill mechanically ventilated patients. The number of mechanically ventilated patients is increasing, placing more patients at risk for these adverse outcomes. Sedation is given to ensure comfort and to minimize distress, but is linked to delirium and immobility. We review recent findings on the management of mechanically ventilated patients focusing on strategies that may improve neurologic and functional outcomes in critically ill patients. We present the evidence-based 'ABCDE' bundle, an integrated and interdisciplinary approach to the management of mechanically ventilated patients. Spontaneous awakening and breathing trials have been combined into 'awake and breathing coordination', shortening the duration of mechanical ventilation, ICU and hospital length of stay and improving survival. The choice of α-2 agonists reduces ICU delirium and duration of mechanical ventilation. Delirium monitoring improves recognition of this disorder, but data on pharmacologic treatment are mixed. Early mobility and exercise may reduce physical dysfunction and delirium rates. Outcomes of critically ill patients can be improved by applying evidence-based therapies for the 'liberation' from mechanical ventilation and sedation, and the 'animation' through early mobilization. Clinicians should be aware of organizational approaches such as the 'ABCDE' bundle to improve the management of mechanically ventilated patients.


Improving Adherence to Cardiovascular Therapies: An Economic Evaluation of a Randomized Pragmatic Trial.
Preplanned economic analysis of a pragmatic trial using electronic-medical-record-linked interactive voice recognition (IVR) reminders for enhancing adherence to cardiovascular medications (i.e., statins, angiotensin-converting enzyme inhibitors [ACEIs], and angiotensin receptor blockers [ARBs]). Three groups, usual care (UC), IVR, and IVR plus educational materials (IVR+), with 21,752 suboptimally adherent patients underwent follow-up for 9.6 months on average. Costs to implement and deliver the intervention (from a payer perspective) were tracked during the trial. Medical care costs and outcomes were ascertained using electronic medical records. Per-patient intervention costs ranged from $9 to $17 for IVR and from $36 to $47 for IVR+. For ACEI/ARB, the incremental cost-effectiveness ratio for each percent adherence increase was about 3 times higher with IVR+ than with IVR ($6 and $16 for IVR and IVR+, respectively). For statins, the incremental cost-effectiveness ratio for each percent adherence increase was about 7 times higher with IVR+ than with IVR ($6 and $43 for IVR and IVR+, respectively). Considering potential cost offsets from reduced cardiovascular events, the probability of breakeven was the highest for UC, but the IVR-based interventions had a higher probability of breakeven for subgroups with a baseline low-density lipoprotein (LDL) level of more than 100 mg/dl and those with two or more calls. We found that the use of an automated voice messaging system to promote adherence to ACEIs/ARBs and statins may be cost-effective, depending on a decision maker's willingness to pay for unit increase in adherence. When considering changes in LDL level and downstream medical care offsets, UC is the optimal strategy for the general population. However, IVR-based interventions may be the optimal choice for those with elevated LDL values at baseline.


Integrin-alpha9 is required for fibronectin matrix assembly during lymphatic valve morphogenesis.
Dysfunction of lymphatic valves underlies human lymphedema, yet the process of valve morphogenesis is poorly understood. Here, we show that during embryogenesis, lymphatic valve leaflet formation is initiated by upregulation of integrin-alpha9 expression and deposition of its ligand fibronectin-EIIIA (FN-EIIIA) in the extracellular matrix. Endothelial cell-specific deletion of Itga9 (encoding integrin-alpha9) in mouse embryos results in the development of rudimentary valve leaflets characterized by disorganized FN matrix, short cusps, and retrograde lymphatic flow. Similar morphological and functional defects are observed in mice lacking the EIIIA domain of FN. Mechanistically, we demonstrate that in primary human lymphatic endothelial cells, the integrin-alpha9-EIIIA interaction directly regulates FN fibril assembly, which is essential for the formation of the extracellular matrix core of valve leaflets. Our findings reveal an important role for integrin-alpha9 signaling during lymphatic valve morphogenesis and implicate it as a candidate gene for primary lymphedema caused by valve defects.


Endoscopic, endonasal extended transsphenoidal, transplanum transtuberculum approach for resection of suprasellar lesions.
The extended transsphenoidal approach is a less invasive method for removing purely suprasellar lesions compared with traditional transcranial approaches. Most advocates have used a sublabial incision and a microscope and have reported a significant risk of cerebrospinal fluid (CSF) leakage. The authors report on a series of purely endoscopic endonasal surgeries for resection of suprasellar supradiaphragmatic lesions above a normal-sized sella turcica with a low risk of CSF leakage. A purely endoscopic endonasal approach was used to remove suprasellar lesions in a series of 10 patients. Five lesions were prechiasmal (three tuberculum sellae and two planum sphenoidale meningiomas) and five were post-chiasmal (four craniopharyngiomas and one Rathke cleft cyst). The floor of the planum sphenoidale and the sella turcica was reconstructed using a multilayer closure with autologous and synthetic materials. Spinal drainage was performed in only five cases. Complete resection of the lesions was achieved in all but one patient. The pituitary stalk was preserved in all but one patient, whose stalk was invaded by a craniopharyngioma and who had preoperative diabetes insipidus (DI). Vision improved postoperatively in all patients with preoperative impairment. Six patients had temporary DI; in five, the DI became permanent. Four patients with craniopharyngiomas required cortisone and thyroid replacement. After a mean follow up of 10 months, there was only one transient CSF leak when a lumbar drain was clamped prematurely on postoperative Day 5. A purely endoscopic endonasal approach to suprasellar supradiaphragmatic lesions is a feasible minimally invasive alternative to craniotomy. With a multilayer closure, the risk of CSF leakage is low and lumbar drainage can be avoided. A larger series will be required to validate this approach.


Same-day antiretroviral therapy is associated with increased loss to follow-up in South African public health facilities: a prospective cohort study of patients diagnosed with HIV.
South Africa introduced Universal Test and Treat in 2016 including antiretroviral therapy (ART) initiation on the same-day as HIV diagnosis. Our study sought to evaluate the impact of same-day ART initiation on loss to follow-up (LTFU) and mortality comparing with patients who initiated ART after their HIV diagnosis. We conducted a file review of patients with a HIV diagnosis and ART start date on file between September 2016 and May 2018 in six high HIV burden districts. Our primary outcome was LTFU (>90 days from the last clinical visit or drug pick-up until database closure 31 July 2018). The secondary outcome was mortality after ART initiation. Time to outcome was assessed comparing same-day vs. one to seven, eight to twenty-one and ≥ twenty-two days to ART initiation using Kaplan-Meier estimators stratified by sex. We investigated predictors using univariate and multivariable Cox proportional hazards models, adjusting for a priori characteristics. Overall, 92,609 ART patients contributed 43,922 person-years from ART initiation, with a median follow-up time of 246 days (IQR = 112 to 455). Of these patients, 33,399 (36%) initiated ART on the same-day as their HIV diagnosis date and had a median follow-up time of 174 days (IQR = 85 to 349). Same-day patients were predominantly non-pregnant females (56%) and aged 25 to 34 years (40%). Same-day ART initiation increased from 2.8% in September 2016 to 7.1% in April 2018. In same-day patients, 33% (n = 11,114) were classified as LTFU with a median time of 55 days (IQR = 1 to 185), compared to 371 mean days (IQR = 161 to 560) in patients who initiated ≥22 days after diagnosis. A similar proportion of LTFU was observed for patients who initiated later: 31% 1 to 21 day and 33% ≥22 day. Same-day ART patients had an increased risk of LTFU vs. ≥1 day (adjusted hazard ratio (aHR) = 1.28, 95% CI = 1.24 to 1.33) adjusting for covariates. Although all-cause mortality was slightly lower in same-day patients (0.9%) vs. >1 day (1.4%; aHR = 0.87, 95% CI = 0.72 to 1.05) adjusting for covariates. Men had highest risk of mortality and LTFU. Same-day ART increased the risk of LTFU, but same-day patients experienced slightly lower mortality. Same-day patients may require additional counselling and interventions to improve retention. Additional research is needed on targeted interventions, including differentiated care, to reduce LTFU in patients initiating ART same-day.


Dietary choices of urban minority high school students.
The purpose of this study was to gather data on the knowledge of nutrition and health, and the dietary choices of minority high school students in an urban setting. Focused group interviews, survey questionnaires, and food diaries were used to obtain information about the food choices made on a daily basis by culturally diverse high school students. The impact of the school meal program, as well as ethnic and cultural patterns, were strong influences in terms of the teens' dietary intake. This study offers insight into the limitations and obstacles to achieving a healthy diet for this population of students.


Pharmacokinetics and Pharmacodynamics of Atazanavir in HIV-1-Infected Children Treated With Atazanavir Powder and Ritonavir: Combined Analysis of the PRINCE-1 and -2 Studies.
Two clinical studies (PRINCE-1 and -2) in HIV-1-infected children assessed the safety, efficacy and pharmacokinetics of dual nucleos(t)ide reverse transcriptase inhibitor background therapy plus once-daily atazanavir (ATV) powder formulation boosted with ritonavir (ATV + RTV). Here, we present a combined analysis of ATV pharmacokinetics and pharmacodynamics across these studies. Intensive 24-hour pharmacokinetic profiles at steady state compared ATV exposures (area under the concentration-time curve in one dosing interval) in 5 ATV + RTV baseline weight-band dosing categories, with historic data in adults receiving ATV + RTV 300/100 mg capsules. Repeated ATV Ctrough measurements over 48 weeks explored relationships between ATV composite Ctrough quartiles (CCQs) with virologic efficacy and key safety parameters. Of 146 children included in this combined analysis, 49.3% were male, 56.8% were Black/African American and 62.3% were antiretroviral experienced. Proportions with HIV-1 RNA <50 copies/mL at week 48 were 13/32, 24/32, 19/32 and 13/28 in the lowest through highest ATV CCQs, respectively. Mean changes from baseline in total bilirubin at week 48 were +0.3, +0.5, +0.6 and +1.0 mg/dL in the lowest through highest ATV CCQs, respectively. Corresponding proportions with adverse events of hyperbilirubinemia by week 48 were 1/36, 4/36, 5/36 and 13/35, respectively. Changes from baseline in total amylase or electrocardiogram parameters and adverse events of diarrhea did not vary by ATV CCQs. Weight-band dosing of ATV + RTV plus optimized dual nucleos(t)ide reverse transcriptase inhibitors in young HIV-1-infected children achieved similar ATV exposure to that in adults; no unexpected safety findings occurred, and with the exception of lower virologic suppression in the lowest ATV CCQ, there was no apparent trend in virologic suppression across ATV CCQs.


Psychometric Properties of the Satisfaction With Life Scale in People With Traumatic Brain, Spinal Cord, or Burn Injury: A National Institute on Disability, Independent Living, and Rehabilitation Research Model System Study.
This study evaluated the measurement properties of the Satisfaction With Life Scale (SWLS) in a sample of 17,897 people with spinal cord injury (48%, n = 8,566), traumatic brain injury (44%, n = 7,941), and burn injury (8%, n = 1,390), 1 year following injury. We examined measurement invariance across the groups, unidimensionality, local independence, reliability from a classical test and item response theory (IRT) framework, and fit to a unidimensional IRT model. The results support unidimensionality and local independence of the SWLS. Reliability was adequate from a classical test and IRT perspective. IRT analysis found that the SWLS could be improved by using only five response categories rather than seven and by removing the fifth item, "If I could live my life over, I would change almost nothing." This item functions poorly and reduces instrument reliability. With these revisions, the SWLS is a useful instrument to monitor an important outcome of trauma rehabilitation.


Noether-Constrained Correlations in Equilibrium Liquids.
Liquid structure carries deep imprints of an inherent thermal invariance against a spatial transformation of the underlying classical many-body Hamiltonian. At first order in the transformation field Noether's theorem yields the local force balance. Three distinct two-body correlation functions emerge at second order, namely the standard two-body density, the localized force-force correlation function, and the localized force gradient. An exact Noether sum rule interrelates these correlators. Simulations of Lennard-Jones, Yukawa, soft-sphere dipolar, Stockmayer, Gay-Berne and Weeks-Chandler-Andersen liquids, of monatomic water and of a colloidal gel former demonstrate the fundamental role in the characterization of spatial structure.


Anti-MDA5 Antibody Dermatomyositis Overlap with Systemic Lupus Erythematosus: A Case Report and Review of the Literature.
Dermatomyositis (DM) is an autoimmune connective tissue disease that primarily targets the muscle, skin, and lungs. Many patients have autoantibodies that correspond to distinct clinical phenotypes. Melanoma differentiation-associated gene 5 (anti-MDA5) antibody, a specific antibody that targets the melanoma differentiation-associated gene 5 (MDA5), has been reported in DM cases and is significant for a distinct cutaneous presentation and rapidly progressive interstitial lung disease. Herein, we describe a patient with DM with a positive anti-MDA5 antibody and characteristic clinical phenotype, who subsequently developed coexisting systemic lupus erythematosus (SLE). A diagnosis of SLE was supported by his clinical phenotype, positive serologies, hypocomplementemia, and progression to glomerulonephritis and lupus cerebritis, features of which fulfilled the American College of Rheumatology criteria for SLE. DM is known to overlap with other autoimmune diseases, including SLE, and coexistence can lead to a wide variety of clinical presentations. SLE overlapping with anti-MDA5 positive DM may present with distinct clinical features.


Preliminary Observations on Skeletal Muscle Adaptation and Plasticity in Homer 2-/- Mice.
Homer represents a diversified family of scaffold and transduction proteins made up of several isoforms. Here, we present preliminary observations on skeletal muscle adaptation and plasticity in a transgenic model of Homer 2-/- mouse using a multifaceted approach entailing morphometry, quantitative RT-PCR (Reverse Transcription PCR), confocal immunofluorescence, and electrophysiology. Morphometry shows that Soleus muscle (SOL), at variance with Extensor digitorum longus muscle (EDL) and Flexor digitorum brevis muscle (FDB), displays sizable reduction of fibre cross-sectional area compared to the WT counterparts. In SOL of Homer 2-/- mice, quantitative RT-PCR indicated the upregulation of Atrogin-1 and Muscle ring finger protein 1 (MuRF1) genes, and confocal immunofluorescence showed the decrease of neuromuscular junction (NMJ) Homer content. Electrophysiological measurements of isolated FDB fibres from Homer 2-/- mice detected the exclusive presence of the adult ε-nAChR isoform excluding denervation. As for NMJ morphology, data were not conclusive, and further work is needed to ascertain whether the null Homer 2 phenotype induces any endplate remodelling. Within the context of adaptation and plasticity, the present data show that Homer 2 is a co-regulator of the normotrophic status in a muscle specific fashion.


Recovery efficiency and limit of detection of aerosolized Bacillus anthracis Sterne from environmental surface samples.
After the 2001 anthrax incidents, surface sampling techniques for biological agents were found to be inadequately validated, especially at low surface loadings. We aerosolized Bacillus anthracis Sterne spores within a chamber to achieve very low surface loading (ca. 3, 30, and 200 CFU per 100 cm(2)). Steel and carpet coupons seeded in the chamber were sampled with swab (103 cm(2)) or wipe or vacuum (929 cm(2)) surface sampling methods and analyzed at three laboratories. Agar settle plates (60 cm(2)) were the reference for determining recovery efficiency (RE). The minimum estimated surface concentrations to achieve a 95% response rate based on probit regression were 190, 15, and 44 CFU/100 cm(2) for sampling steel surfaces and 40, 9.2, and 28 CFU/100 cm(2) for sampling carpet surfaces with swab, wipe, and vacuum methods, respectively; however, these results should be cautiously interpreted because of high observed variability. Mean REs at the highest surface loading were 5.0%, 18%, and 3.7% on steel and 12%, 23%, and 4.7% on carpet for the swab, wipe, and vacuum methods, respectively. Precision (coefficient of variation) was poor at the lower surface concentrations but improved with increasing surface concentration. The best precision was obtained with wipe samples on carpet, achieving 38% at the highest surface concentration. The wipe sampling method detected B. anthracis at lower estimated surface concentrations and had higher RE and better precision than the other methods. These results may guide investigators to more meaningfully conduct environmental sampling, quantify contamination levels, and conduct risk assessment for humans.