The natural course of anxiety disorders in the elderly: a systematic review of longitudinal trials.
The anxiety disorders are a prevalent mental health problem in older age with a considerable impact on quality of life. Until recently there have been few longitudinal studies on anxiety in this age group, consequently most of the evidence to date has been cross-sectional in nature. We undertook a literature search of Medline, PsycINFO, the Cochrane trials database and the TRIP medical database to identify longitudinal studies which would help elucidate natural history and prognosis of anxiety disorders in the elderly. We identified 12 papers of 10 longitudinal studies in our Review. This represented 34,691 older age participants with 5,199 with anxiety disorders including anxious depression and 3,532 individuals with depression without anxiety. Relapse rates of anxiety disorders are high over 6 year follow-up with considerable migration to mixed anxiety-depression and pure depressive mood episodes. Mixed anxiety-depression appears to be a poorer prognostic state than pure anxiety or pure depression with higher relapse rates across studies. In community settings treatment rates are low with 7-44% of the anxious elderly treated on antidepressant medications. To our knowledge this is the first Systematic Review of longitudinal trials of anxiety disorders in older people. Major longitudinal studies of the anxious elderly are establishing the high risk of relapse and persistence alongside the progression to depression and anxiety depression states. There remains considerable under-treatment in community studies. Specialist assessment and treatment and major public health awareness of the challenges of anxiety disorders in the elderly are required.


[Chronic pancreatis and pancreatic carcinoma in the elderly].
Chronic pancreatitis is mostly caused by heavy alcohol consumption and is characterized by the onset of symptoms in the fourth and fifth decade. Beginning in patients older than 65 years of age is rare. Leading symptom is recurrent or persisting abdominal pain which is missed only in approximately 5% of the cases. Chronic pancreatitis is classified as idiopathic if there is no anamnesis of alcohol abuse or some rare specific causes. The Idiopathic Chronic Senile Pancreatitis (ICSP) is a subset of the non-alcoholic pancreatitis and is characterized by advanced age at the time of first manifestation. Although life expectancy especially in chronic alcoholic pancreatitis is reduced, there are many patients who reach older age. The natural history in all forms of chronic pancreatitis shows a decrease in pain and the manifestation of exocrine and endocrine insufficiency as late complications. Especially in the elderly loss of weight may occur with steatorrhea and pancreatic diabetes mellitus as the dominating clinical problem of chronic pancreatitis. If pain persists treatment is symptomatically with analgesics. The possibility of causal surgery or the indication for endoscopic treatment of painful chronic pancreatitis should be proven in every single case. Standard pancreatin treatment consisting of large amounts of enzymes will abolish maldigestion. Pancreatic diabetes requires often insulin, there is a tendency to hypoglycaemia. In contrast to chronic pancreatitis cancer of the pancreas is a typical and frequent disease of the elderly. The prognosis is bad and one year life expectancy is just about 11%. One of the reasons is, that the diagnosis is found lately because early symptoms are missing. Specific symptoms like pain, weight loss or jaundice occur lately. In suspicion of pancreatic cancer a lot of methods of morphological diagnostic are available such as CT, MRCP, ultrasound, ERCP and PET, in addition the specific tumor markers CA 19-9 and CEA. After diagnostic is completed, curative resection is possible in only a low percentage of all cases. Old age is no contraindication for surgery, prognosis and the risk of surgery don't differ to other age groups. In most cases palliative therapy is the only possible option because of an advanced tumor stage. Sufficient pain therapy, endoscopic stenting in case of obstructive jaundice or gastroenterostomy in case of duodenal are useful interventions.


Effect of body mass index and physical exercise on risk of knee and hip osteoarthritis: longitudinal data from the Norwegian HUNT Study.
Mechanical joint stress imposed by high body mass index (BMI) is associated with increased risk of knee and hip osteoarthritis. This prospective study investigated the independent and joint association of BMI and physical exercise on risk of knee and hip osteoarthritis. The study includes 15,191 women and 14,766 men in the Norwegian HUNT Study without pain or physical impairment at baseline. Occurrence of self-reported physician-diagnosed osteoarthritis was assessed at 11 years of follow-up. BMI was positively related to risk of knee osteoarthritis (P(trend)<0.001), with an RR of 4.37 (95% CI 3.01 to 6.33) in women and 2.78 (95% CI 1.59 to 4.84) in men, comparing obese and normal weight persons. No clear association was observed for hip osteoarthritis. Obesity increased the risk of severe activity-limiting osteoarthritis, with an RR of 2.30 (95% CI 1.68 to 3.15) and 2.50 (95% CI 1.56 to 4.03) in women and men, respectively. Physical exercise did not modify the above associations (P(interaction)>0.34). Exercise intensity was not associated with risk of osteoarthritis in any BMI category; that is, obese persons reporting high-intensity exercise had an RR of 1.28 (95% CI 0.59 to 2.79) for severe osteoarthritis compared with inactive persons. High BMI increases the risk of knee osteoarthritis and severe osteoarthritis. Physical exercise does not increase the risk of osteoarthritis at any level of BMI, suggesting that exercise could be encouraged also among individuals with excessive body mass, without concern for an increased risk of osteoarthritis.


Identifying predictors of psychological well-being among volunteer mentors in Big Brothers Big Sisters.
Big Brothers Big Sisters (BBBS) facilitates mentoring relationships between youth and volunteer mentors. Although research has examined outcomes for youth in BBBS, relatively less investigation has been undertaken for volunteer outcomes. This study explored factors associated with changes in psychological well-being among BBBS volunteer mentors. Participants included 593 mentors (Mage = 31) surveyed at study baseline and 15-month follow-up. A classification and regression decision tree approach was used to predict residualized change in psychological well-being from study baseline with match length included as the first split variable, and demographic, individual, and relationship variables included as candidate predictors. Analyses indicated that mentors with longer relationships (>4.5 months) reported more positive change in psychological well-being compared with mentors with shorter relationships. Perceived quality of program supervision was a further predictor within both groups of volunteers. Findings suggest that longer relationships and greater program support may contribute to mentor well-being.


Marigold Supercritical Extract as Potential Co-adjuvant in Pancreatic Cancer: The Energetic Catastrophe Induced via BMP8B Ends Up With Autophagy-Induced Cell Death.
The recent development of powerful "omics" technologies (genomics, transcriptomics, proteomics, metabolomics, and lipidomics) has opened new avenues in nutritional sciences toward precision nutrition, which is a genotype-directed nutrition that takes into account the differential responses to nutritional interventions based on gene variation (nutrigenetics) and the effect of nutrients on gene expression (nutrigenomics). Current evidence demonstrates that up to one third of the deaths caused by cancer could be prevented by acting on key risk factors, with diet being one of the most important risk factors due to its association with obesity. Additional factors such as composition of gut microbiome, the immune system, and the nutritional status will have an impact on the final outcome. Nutrient components and bioactive compounds from natural sources can have an impact on cancer progression or even the risk of cancer development by regulating gene expression and/or associated risk factors such as obesity and chronic inflammation. Nowadays, among the different methods to produce natural extracts, the green technology of supercritical fluid extraction (SFE) is quite popular, with a special interest on the use of supercritical CO2 for the extraction of compounds with low polarity. The success of nutritional interventions based on the use of nutraceuticals requires several steps: (i) in vitro and preclinical demonstration of their antitumoral effects; (ii) knowledge of their mechanism of action and molecular targets, which will allow for identification of the specific subgroups of patients who will benefit from them; (iii) the study of genetic variants associated with the differential responses; and (iv) innovative approaches of formulations to improve the in vivo bioavailability of the bioactive ingredients. Herein, we investigate the antitumoral properties and mechanism of action of a supercritical CO2 extract from Calendula officinalis, commonly known as marigold (marigold SFE) in the context of pancreatic cancer. Mechanistically, marigold SFE induces the expression of BMP8B, which leads to an energetic catastrophe ending up with autophagy-induced cell death (AICD). As metabolic reprogramming is a well-recognized hallmark of cancer, the direct impact of marigold SFE on pancreatic cancer cell metabolism encourages further research of its potential as a coadjuvant in pancreatic cancer therapy. Finally, we discuss innovative formulation approaches to augment the clinical therapeutic potential of marigold SFE in nutritional interventions.


The blood-testis barrier in sterile blue fox - silver fox hybrids compared with that in normal foxes of both species.
The integrity of the blood-testis barrier in the blue fox, the silver fox and hybrids of these 2 species was compared at the ultrastructural level during the breeding season by use of a lanthanum penetration technique. In the normal blue and silver fox, penetration of the tracer was blocked at the level of the inter-Sertoli cell junctions, whereas these junctions were permeable in the hybrids, permitting penetration of lanthanum into the adluminal compartment of the seminiferous epithelium. Spermatogenesis in the hybrids was found to be arrested at the early pachytene stage of meiotic prophase. The observed permeability of the inter-Sertoli cell contacts in the hybrids indicates a lack of occluding junctions, and this may be partly the cause of the sterility in these animals.


Modulation of Arabidopsis root growth by specialized triterpenes.
Plant roots are specialized belowground organs that spatiotemporally shape their development in function of varying soil conditions. This root plasticity relies on intricate molecular networks driven by phytohormones, such as auxin and jasmonate (JA). Loss-of-function of the NOVEL INTERACTOR OF JAZ (NINJA), a core component of the JA signaling pathway, leads to enhanced triterpene biosynthesis, in particular of the thalianol gene cluster, in Arabidopsis thaliana roots. We have investigated the biological role of thalianol and its derivatives by focusing on Thalianol Synthase (THAS) and Thalianol Acyltransferase 2 (THAA2), two thalianol cluster genes that are upregulated in the roots of ninja mutant plants. THAS and THAA2 activity was investigated in yeast, and metabolite and phenotype profiling of thas and thaa2 loss-of-function plants was carried out. THAA2 was shown to be responsible for the acetylation of thalianol and its derivatives, both in yeast and in planta. In addition, THAS and THAA2 activity was shown to modulate root development. Our results indicate that the thalianol pathway is not only controlled by phytohormonal cues, but also may modulate phytohormonal action itself, thereby affecting root development and interaction with the environment.


Nucleotide sequence of cloned cDNA specific for rat ribosomal protein L31.
A cDNA clone, specific for rat ribosomal protein L31, was isolated by hybrid-selected translation from a cDNA library made for 8-9-S poly(A)-rich RNA from regenerating rat liver. The nucleotide sequence of the cDNA was determined. It consists of 25 base pairs from the 5' leading sequence, the entire coding sequence of 378 base pairs and the 3' trailing sequence of 36 base pairs besides the poly(A) tail. The primary structure of protein L31 was deduced from the nucleotide sequence. It consists of 124 amino acids with a relative molecular mass of 14,331. The calculated amino acid composition is consistent with the reported composition determined for the hydrolysate of L31. The amino acid sequence showed marked homology with that of yeast ribosomal protein L34.


The Biological Deserts Fallacy: Cities in Their Landscapes Contribute More than We Think to Regional Biodiversity.
Cities are both embedded within and ecologically linked to their surrounding landscapes. Although urbanization poses a substantial threat to biodiversity, cities also support many species, some of which have larger populations, faster growth rates, and higher productivity in cities than outside of them. Despite this fact, surprisingly little attention has been paid to the potentially beneficial links between cities and their surroundings. We identify five pathways by which cities can benefit regional ecosystems by releasing species from threats in the larger landscape, increasing regional habitat heterogeneity and genetic diversity, acting as migratory stopovers, preadapting species to climate change, and enhancing public engagement and environmental stewardship. Increasing recognition of these pathways could help cities identify effective strategies for supporting regional biodiversity conservation and could provide a science-based platform for incorporating biodiversity alongside other urban greening goals.


Hyponatremia and hypoglycemia in acute Sheehan's syndrome.
We report the case of a 23-year-old Saudi Arabian woman who presented to the medical intensive care unit with severe hyponatremia and hypoglycemia following a Cesarean section delivery complicated by hemorrhage due to disseminated intravascular coagulopathy. She was treated successfully for adrenal insufficiency acutely, and was later discharged on hormone replacement therapy. To our knowledge, this is the first case report of acute Sheehan's syndrome presenting with both hyponatremia and suggestive hypoglycemia. Pituitary necrosis is an uncommon complication of peripartum hemorrhagic shock. Since the initial description by Sheehan in 1937, the incidence of the syndrome has gradually declined through improved management of hemodynamic complications leading to the infarction of the gland. There are many studies describing complications of late Sheehan's syndrome; however, relatively few contain descriptions of the acute phase. In addition, the diagnosis of this syndrome is often determined after resolution of the acute process with resultant lack of data regarding immediate endocrine and imaging abnormalities. In this report, we describe the complete endocrine and imaging assessment of a patient presenting in critical condition due to necrosis of the pituitary gland in the immediate postpartum period.


A novel allele of Saccharomyces cerevisiae RFA1 that is deficient in recombination and repair and suppressible by RAD52.
To understand the mechanisms involved in homologous recombination, we have performed a search for Saccharomyces cerevisiae mutants unable to carry out plasmid-to-chromosome gene conversion. For this purpose, we have developed a colony color assay in which recombination is induced by the controlled delivery of double-strand breaks (DSBs). Recombination occurs between a chromosomal mutant ade2 allele and a second plasmid-borne ade2 allele where DSBs are introduced via the site-specific HO endonuclease. Besides isolating a number of new alleles in known rad genes, we identified a novel allele of the RFA1 gene, rfa1-44, which encodes the large subunit of the heterotrimeric yeast single-stranded DNA-binding protein RPA. Characterization of rfa1-44 revealed that it is, like members of the RAD52 epistasis group, sensitive to X rays, high doses of UV, and HO-induced DSBs. In addition, rfa1-44 shows a reduced ability to undergo sporulation and HO-induced gene conversion. The mutation was mapped to a single-base substitution resulting in an aspartate at amino acid residue 77 instead of glycine. Moreover, all radiation sensitivities and repair defects of rfa1-44 are suppressed by RAD52 in a dose-dependent manner, and one RAD52 mutant allele, rad52-34, displays nonallelic noncomplementation when crossed with rfa1-44. Presented is a model accounting for this genetic interaction in which Rfa1, in a complex with Rad52, serves to assemble other proteins of the recombination-repair machinery at the site of DSBs and other kinds of DNA damage. We believe that our findings and those of J. Smith and R. Rothstein (Mol. Cell. Biol. 15:1632-1641, 1995) are the first in vivo demonstrations of the involvement of a eukaryotic single-stranded binding protein in recombination and repair processes.


Life in the human stomach: persistence strategies of the bacterial pathogen Helicobacter pylori.
The bacterial pathogen Helicobacter pylori has co-evolved with humans and colonizes approximately 50% of the human population, but only causes overt gastric disease in a subset of infected hosts. In this Review, we discuss the pathogenesis of H. pylori and the mechanisms it uses to promote persistent colonization of the gastric mucosa, with a focus on recent insights into the role of the virulence factors vacuolating cytotoxin (VacA), cytotoxin-associated gene A (CagA) and CagL. We also describe the immunobiology of H. pylori infection and highlight how this bacterium manipulates the innate and adaptive immune systems of the host to promote its own persistence.


Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease-modifying anti-rheumatic drugs (SELECT-BEYOND): a double-blind, randomised controlled phase 3 trial.
Phase 2 studies with upadacitinib, a selective Janus kinase 1 (JAK1) inhibitor, have shown safety and efficacy in the treatment of patients with active rheumatoid arthritis. We did this study to further assess the safety and efficacy of upadacitinib in patients with an inadequate response to biologic disease-modifying anti-rheumatic drugs (bDMARDs). We did this double-blind, randomised controlled phase 3 trial at 153 sites in 26 countries. Patients were aged 18 years or older, had active rheumatoid arthritis and previous inadequate response or intolerance to bDMARDs, and were receiving concomitant background conventional synthetic DMARDS (csDMARDs). We randomly assigned patients (2:2:1:1) by interactive response technology to receive once-daily oral extended-release upadacitinib 15 mg or 30 mg or placebo for 12 weeks, followed by upadacitinib 15 mg or 30 mg from week 12 onwards. The two separate primary endpoints were the proportions of patients achieving a 20% improvement in American College of Rheumatology criteria (ACR20) at week 12 and the proportion of patients achieving a 28-joint disease activity score using C-reactive protein (DAS28[CRP]) of 3·2 or less at week 12. Efficacy and safety analyses were done in the modified intention-to-treat population of all patients who received at least one dose of study drug. Data are presented up to week 24 of this ongoing study. The trial is registered with ClinicalTrials.gov (NCT02706847). Between March 15, 2016, and Jan 10, 2017, 499 patients were randomly assigned (n=165 upadacitinib 15 mg; n=165 upadacitinib 30 mg; n=85 placebo then upadacitinib 15 mg; and n=84 placebo then upadacitinib 30 mg) and one patient was withdrawn from the 15 mg upadacitinib group before the start of study treatment. Mean disease duration was 13·2 years (SD 9·5); 235 (47%) of 498 patients had received one previous bDMARD, 137 (28%) had received two, and 125 (25%) had received at least three; 451 (91%) patients completed treatment up to week 12 and 419 (84%) patients completed treatment up to week 24. At week 12, ACR20 was achieved by 106 (65%; 95% CI 57-72) of 164 patients receiving upadacitinib 15 mg and 93 (56%; 49-64) of 165 patients receiving upadacitinib 30 mg compared with 48 (28%; 22-35) of 169 patients receiving placebo (p<0·0001 for each dose vs placebo). DAS28(CRP) of 3·2 or less was achieved by 71 (43%; 95% CI 36-51) of 164 patients receiving upadacitinib 15 mg and 70 (42%; 35-50) of 165 patients receiving upadacitinib 30 mg versus 24 (14%; 9-20) of 169 patients receiving placebo (p<0·0001 for each dose vs placebo). Up to week 12, overall numbers of patients with adverse events were similar for the placebo group (95 [56%] of 169) and the upadacitinib 15 mg group (91 [55%] of 164), but higher in the upadacitinib 30 mg group (111 [67%] of 165). At week 12, the most common adverse events occurring in at least 5% of patients in any treatment group were upper respiratory tract infection (13 [8%] of 169 in the placebo group; 13 [8%] of 164 in the upadacitinib 15 mg group; ten [6%] of 165 in the upadacitinib 30 mg group), nasopharyngitis (11 [7%]; seven [4%]; nine [5%]), urinary tract infection (ten [6%]; 15 [9%]; nine [5%]), and worsening of rheumatoid arthritis (ten [6%]; four [2%]; six [4%]). The number of patients with serious adverse events was higher in the upadacitinib 30 mg group (12 [7%]) than in the upadacitinib 15 mg group (eight [5%]); no serious adverse events were reported in patients receiving placebo. More patients in the upadacitinib 30 mg group had serious infections, herpes zoster, and adverse events leading to discontinuation than in the upadacitinib 15 mg and placebo groups. During the placebo-controlled phase of the study, one case of pulmonary embolism, three malignancies, one major adverse cardiovascular event, and one death were reported in patients receiving upadacitinib; none were reported in patients receiving placebo. Both doses of upadacitinib led to rapid and significant improvements compared with placebo over 12 weeks in patients with refractory rheumatoid arthritis. AbbVie Inc.


NSAID consumption and risk of acute myeloid leukemia: a national population-based case-control study.
Most cases of acute leukemia arise without identifiable risk factors. Studies investigating the impact of autoimmune diseases and infections on leukemogenesis have revealed conflicting results. If inflammation increases the risk of acute myeloid leukemia (AML), nonsteroidal anti-inflammatory drug (NSAID) use may decrease the risk of leukemia. We conducted a case-control study of 3,053 patients with AML diagnosed between 2000 and 2013, who were registered in the Danish National Acute Leukemia Registry, and 30,530 population controls matched on sex and age. We identified prescriptions through the Danish National Health Service Prescription Database. We used conditional logistic regression analysis to compute ORs associating AML with NSAID use overall, in patients with inflammatory diseases, and for specific AML subtypes (de novo AML, AML related to previous hematological disease, ie, secondary AML [sAML], or therapy-related AML [tAML; exposed to previous cytotoxic therapy]). Overall, NSAID use was not associated with a lower risk of AML (OR 1.1, 95% CI=1.0-1.2), de novo AML (OR 1.0, 95% CI=0.9-1.1), and sAML/tAML (OR 1.3, 95% CI=1.1-1.5). In addition, in patients with known inflammatory diseases, NSAIDs did not affect AML risk (OR 0.9, 95% CI=0.5-1.6). Number of prescriptions, type of NSAID, age, or sex did not influence the results. In line with our recent findings that showed no association between autoimmune diseases and infections and de novo AML, NSAID use was not found to reduce the risk of AML.


Hypocholesterolemic effect of β-caryophyllene in rats fed cholesterol and fat enriched diet.
Hypercholesterolemia is a major risk factor for cardiovascular diseases. This study investigated the cholesterol-lowering potential of β-caryophyllene in a rat model. Hypercholesterolemia was induced by feeding male Wistar rats a high cholesterol and fat diet for 2 weeks. This was followed by oral administration of β-caryophyllene to hypercholesterolemic rats at 30, 100 and 300 mg/kg b.w. for 4 weeks. A dose of 30 mg/kg of β-caryophyllene significantly lowered serum total cholesterol, low density lipoprotein and the atherogenic index and significantly increased high density lipoprotein level. Moreover, it ameliorated liver injury as evidenced by decreasing hepatomegaly, macrovesicular steatosis and the activity of hepatic marker enzymes alanine aminotransferase and aspartate aminotransferase. Furthermore, it increased the activity of the antioxidant enzyme superoxide dismutase. This dose of β-caryophyllene significantly inhibited the activity of hepatic hydroxy-methylglutaryl coenzyme A reductase. Higher doses (100 and 300 mg/kg) of β-caryophyllene, however, did not induce significant beneficial effects on the studied parameters. These observations demonstrate that β-caryophyllene has a cholesterol-lowering effect on hypercholesterolemic rats, thus offering protection against hypercholesterolemia-induced diseases such as atherosclerosis and fatty liver.


Antioxidants and periodontitis in 60-70-year-old men.
The aim was to investigate the association between periodontal health and the serum levels of various antioxidants including carotenoids, retinol and vitamin E in a homogenous group of Western European men. A representative sample of 1258 men aged 60-70 years, drawn from the population of Northern Ireland, was examined between 2001 and 2003. Each participant had six or more teeth, completed a questionnaire and underwent a clinical periodontal examination. Serum lipid-soluble antioxidant levels were measured by high-performance liquid chromatography with diode array detection. Multivariable analysis was carried out using logistic regression with adjustment for possible confounders. Models were constructed using two measures of periodontal status (low- and high-threshold periodontitis) as dependent variables and the fifths of each antioxidant as a predictor variable. The levels of alpha- and beta-carotene, beta-cryptoxanthin and zeaxanthin were highly significantly lower in the men with low-threshold periodontitis (p<0.001). These carotenoids were also significantly lower in high-threshold periodontitis. There were no significant differences in the levels of lutein, lycopene, alpha- and gamma-tocopherol or retinol in relation to periodontitis. In fully adjusted models, there was an inverse relationship between a number of carotenoids (alpha- and beta-carotene and beta-cryptoxanthin) and low-threshold periodontitis. beta-Carotene and beta-cryptoxanthin were the only antioxidants that were associated with an increased risk of high-threshold severe periodontitis. The adjusted odds ratio for high-threshold periodontitis in the lowest fifth relative to the highest fifth of beta-cryptoxanthin was 4.02 (p=0.003). It is concluded that low serum levels of a number of carotenoids, in particular beta-cryptoxanthin and beta-carotene, were associated with an increased prevalence of periodontitis in this homogenous group of 60-70-year-old Western European men.


Up-regulation of NMDA receptor subunit and post-synaptic density protein expression in the thalamus of elderly patients with schizophrenia.
Numerous studies have described structural and functional abnormalities of the thalamus in schizophrenia, but surprisingly few studies have examined neurochemical abnormalities that accompany these pathological changes. We previously identified abnormalities of multiple molecules associated with glutamatergic neurotransmission, including changes in NMDA receptor subunit transcripts and binding sites and NMDA receptor-associated post-synaptic density (PSD) protein transcripts in the thalamus of elderly patients with schizophrenia. In the present study, we performed western blot analysis to determine whether protein levels of NMDA receptor subunits (NR1, NR2A, NR2B) and associated PSD proteins (NF-L, PSD95, SAP102) are altered in schizophrenia. Thalamic tissue from each subject was grossly dissected into two regions: a dorsomedial region containing limbic-associated dorsomedial, anterior and central medial thalamic nuclei; and a ventral thalamus region that primarily consisted of the ventral lateral nucleus. We observed increased protein expression of the NR2B NMDA receptor subunit and its associated intracellular protein, PSD95, in the dorsomedial thalamus of patients with schizophrenia, but the other molecules were unchanged, and we found no changes in the ventral thalamus. These data provide additional evidence of thalamic neurochemical abnormalities, particularly in thalamic nuclei which project to limbic regions of the brain. Further, these findings provide additional evidence of NMDA receptor alterations in schizophrenia, which may play an important role in the neurobiology of the illness.


Real-imaging cDNA-AFLP transcript profiling of pancreatic cancer patients: Egr-1 as a potential key regulator of muscle cachexia.
Cancer cachexia is a progressive wasting syndrome and the most prevalent characteristic of cancer in patients with advanced pancreatic adenocarcinoma. We hypothesize that genes expressed in wasted skeletal muscle of pancreatic cancer patients may determine the initiation and severity of cachexia syndrome. We studied gene expression in skeletal muscle biopsies from pancreatic cancer patients with and without cachexia utilizing Real-Imaging cDNA-AFLP-based transcript profiling for genome-wide expression analysis. Our approach yielded 183 cachexia-associated genes. Ontology analysis revealed characteristic changes for a number of genes involved in muscle contraction, actin cytoskeleton rearrangement, protein degradation, tissue hypoxia, immediate early response and acute-phase response. We demonstrate that Real-Imaging cDNA-AFLP analysis is a robust method for high-throughput gene expression studies of cancer cachexia syndrome in patients with pancreatic cancer. According to quantitative RT-PCR validation, the expression levels of genes encoding the acute-phase proteins α-antitrypsin and fibrinogen α and the immediate early response genes Egr-1 and IER-5 were significantly elevated in the skeletal muscle of wasted patients. By immunohistochemical and Western immunoblotting analysis it was shown, that Egr-1 expression is significantly increased in patients with cachexia and cancer. This provides new evidence that chronic activation of systemic inflammatory response might be a common and unifying factor of muscle cachexia.


[Multiple hematogenic osteomyelitis in children].
The work presents an analysis of 27 cases of acute hematogenic osteomyelitis with multiple injuries of bones. It has been noted that unlike primary localizations which often turn into a chronic process the secondary foci in such patients are frequently treated with good long-term issues. Lethality among patients with multiple osteomyelitis according to the authors' data is considerably higher (26%) than that in patients with the injury of one bone (0,8%).


Na+ entry through heteromeric TRPC4/C1 channels mediates (-)Englerin A-induced cytotoxicity in synovial sarcoma cells.
The sesquiterpene (-)Englerin A (EA) is an organic compound from the plant Phyllanthus engleri which acts via heteromeric TRPC4/C1 channels to cause cytotoxicity in some types of cancer cell but not normal cells. Here we identified selective cytotoxicity of EA in human synovial sarcoma cells (SW982 cells) and investigated the mechanism. EA induced cation channel current (Icat) in SW982 cells with biophysical characteristics of heteromeric TRPC4/C1 channels. Inhibitors of homomeric TRPC4 channels were weak inhibitors of the Icat and EA-induced cytotoxicity whereas a potent inhibitor of TRPC4/C1 channels (Pico145) strongly inhibited Icat and cytotoxicity. Depletion of TRPC1 converted Icat into a current with biophysical and pharmacological properties of homomeric TRPC4 channels and depletion of TRPC1 or TRPC4 suppressed the cytotoxicity of EA. A Na+/K+-ATPase inhibitor (ouabain) potentiated EA-induced cytotoxicity and direct Na+ loading by gramicidin-A caused Pico145-resistant cytotoxicity in the absence of EA. We conclude that EA has a potent cytotoxic effect on human synovial sarcoma cells which is mediated by heteromeric TRPC4/C1 channels and Na+ loading.


Identification of Implementation Strategies Used for the Circle of Security-Virginia Family Model Intervention: Concept Mapping Study.
A reoccurring finding from health and clinical services is the failure to implement theory and research into practice and policy in appropriate and efficient ways, which is why it is essential to develop and identify implementation strategies, as they constitute the how-to component of translating and changing health practices. The aim of this study was to provide a systematic and comprehensive review of the implementation strategies that have been applied for the Circle of Security-Virginia Family (COS-VF) model by developing an implementation protocol. First, informal interviews and documents were analyzed using concept mapping to identify implementation strategies. All documentation from the Network for Infant Mental Health's work with COS-VF was made available and included for analysis, and the participants were interviewed to validate the findings and add information not present in the archives. To avoid lack of clarity, an existing taxonomy of implementation strategies, the Expert Recommendations for Implementing Change, was used to conceptualize (ie, name and define) strategies. Second, the identified strategies were specified according to Proctor and colleagues' recommendations for reporting in terms of seven dimensions: actor, the action, action targets, temporality, dose, implementation outcomes, and theoretical justification. This ensures a full description of the implementation strategies and how these should be used in practice. Ten implementation strategies were identified: (1) develop educational materials, (2) conduct ongoing training, (3) audit and feedback, (4) make training dynamic, (5) distribute educational materials, (6) mandate change, (7) obtain formal commitments, (8) centralize technical assistance, (9) create or change credentialing and licensure standards, and (10) organize clinician implementation team meetings. This protocol provides a systematic and comprehensive overview of the implementation of the COS-VF in health services. It constitutes a blueprint for the implementation of COS-VF that supports the interpretation of subsequent evaluation studies, facilitates knowledge transfer and reproducibility of research results in practice, and eases the replication and comparison of implementation strategies in COS-VF and other interventions.


A Fas-based suicide switch in human T cells for the treatment of graft-versus-host disease.
Graft-versus-host disease (GVHD) is a major complication of allogeneic bone marrow transplantation. One strategy to treat GVHD is to equip donor T cells with a conditional suicide mechanism that can be triggered when GVHD occurs. The herpes simplex virus thymidine kinase (HSV-tk)/ganciclovir system used clinically has several limitations, including immunogenicity and cell cycle dependence. An alternative switch based on chemically inducible apoptosis was designed and evaluated. A chimeric human protein was expressed comprising an extracellular marker (DeltaLNGFR), the Fas intracellular domain, and 2 copies of an FK506-binding protein (FKBP). Primary human T lymphocytes retrovirally transduced with this construct could be purified to homogeneity using immunomagnetic beads. Genetic integrity of the construct was ensured by redesigning repetitive sequences. Transduced T cells behaved indistinguishably from untransduced cells, retaining the ability to mount a specific antiallogeneic immune response. However, they rapidly underwent apoptosis with the addition of subnanomolar concentrations of AP1903, a bivalent "dimerizer" drug that binds FKBP and induces Fas cross-linking. A single 2-hour treatment eliminated approximately 80% of T cells, and multiple exposures induced further apoptosis. T cells were eliminated regardless of their proliferation state, suggesting that the AP1903/Fas system, which contains only human components, is a promising alternative to HSV-tk for treating GVHD.


Comprehensive characterization of MHC class II haplotypes in Mauritian cynomolgus macaques.
There are currently no nonhuman primate models with fully defined major histocompatibility complex (MHC) class II genetics. We recently showed that six common MHC haplotypes account for essentially all MHC diversity in cynomolgus macaques (Macaca fascicularis) from the island of Mauritius. In this study, we employ complementary DNA cloning and sequencing to comprehensively characterize full length MHC class II alleles expressed at the Mafa-DPA, -DPB, -DQA, -DQB, -DRA, and -DRB loci on the six common haplotypes. We describe 34 full-length MHC class II alleles, 12 of which are completely novel. Polymorphism was evident at all six loci including DPA, a locus thought to be monomorphic in rhesus macaques. Similar to other Old World monkeys, Mauritian cynomolgus macaques (MCM) share MHC class II allelic lineages with humans at the DQ and DR loci, but not at the DP loci. Additionally, we identified extensive sharing of MHC class II alleles between MCM and other nonhuman primates. The characterization of these full-length-expressed MHC class II alleles will enable researchers to generate MHC class II transferent cell lines, tetramers, and other molecular reagents that can be used to explore CD4+ T lymphocyte responses in MCM.


3-D spot modeling for automatic segmentation of cDNA microarray images.
Spot segmentation--the second essential stage of cDNA microarray image analysis--constitutes a challenging process. At present, several up-to-date spot-segmentation techniques or software programs--proposed in the literature--are often characterized as "automatic." On the contrary, they are in effect not fully automatic since they require human intervention in order to specify mandatory input parameters or to correct their results. Human intervention, however, can inevitably modify the actual results of the cDNA microarray experiment and lead to erroneous biological conclusions. Therefore, the development of an automated spot-segmentation process becomes of exceptional interest. In this paper, an original and fully automatic approach to accurately segmenting the spots in a cDNA microarray image is presented. In order for the segmentation to be accomplished, each real spot of the cDNA microarray image is represented in a three-dimensional (3-D) space by a 3-D spot model. Each 3-D spot model is determined via an optimization problem, which is solved by using a genetic algorithm. The segmentation of real spots is conducted by drawing the contours of their 3-D spot models. The proposed method has been compared with various published and established techniques, using several synthetic and real cDNA microarray images that contain thousands of spots. The outcome has shown that the proposed method outperforms prevalent existing techniques. It is also noise resistant and yields excellent results even under adverse conditions such as the appearance of spots of various sizes and shapes.


Training characteristics of paralympic swimmers.
The ability to monitor training is critical to the process of quantifying training periodization plans, yet weekly patterns of volume and intensity for Paralympic swimmers before competition have not been reported. Sixteen swimmers were monitored prospectively over a 16-week training block constituting 4 training phases (early, mid, late, and taper), before a World Championship. Training volume (total and main set distance) and intensity (percentage of peak heart rate [HR], swimming velocity, and rate of perceived exertion [RPE]) were quantified using an online training diary, and changes in training load were examined over the 4 training phases. For a subgroup of swimmers (n = 12), with similarities in underlying disability, change in performance between Selection Trials and World Championships was also quantified. Substantial increases in total training volume (29.6%) were observed late phase, and main set volume was reduced substantially (24.1%) during the taper phase. Small to moderate increases in training intensity (HR 2.4%, velocity 4.5%, and RPE 6.7%) were observed late phase and maintained through the taper. There were no clear associations between discrete training measures and competition performance. Swimmers competing at the Paralympic level seem to follow traditional periodized patterns of training, similar to those of swimmers at the Olympic level, before competition. Coaches of elite swimmers with a disability should review their prescribed patterns of training before major competition: A more substantial taper (larger reduction in volume) could elicit a greater improvement in performance. Training prescription should account for different disabilities and classes and individual circumstances of elite swimmers with a disability.


Lysophosphatidic acid upregulates the epidermal growth factor receptor in human airway smooth muscle cells.
Human airway smooth muscle cells treated with lysophosphatidic acid (LPA) and epidermal growth factor (EGF) exhibit synergistic stimulation of mitogenesis (Ediger TL and Toews ML. J Pharmacol Exp Ther 294: 1076-1082, 2000). The effects of LPA treatment of human airway smooth muscle cells on EGF receptor (EGFR) regulation have now been investigated. LPA treatment for 12-24 h resulted in a twofold increase in (125)I-EGF binding and EGFR protein levels as assessed by Western blot analysis. Competition binding assays indicated single-site binding with an affinity of 3 nM, and the affinity was not changed by LPA treatment. EGFR upregulation was blocked by cycloheximide and actinomycin D, suggesting that LPA influences transcriptional regulation of EGFR expression. Inhibitor studies revealed a prominent role for activation of mitogen-activated protein kinase and p70 ribosomal S6 kinase. Both synergism and EGFR upregulation increased with increased cell density, whereas EGFR expression in control cells decreased. The similar requirements for exposure time, LPA concentrations, and cell confluence suggest that EGFR upregulation may be one contributing factor to the synergistic stimulation of mitogenesis seen with LPA plus EGF.


The Many Faces of Post-Ischemic Tau Protein in Brain Neurodegeneration of the Alzheimer's Disease Type.
Recent data suggest that post-ischemic brain neurodegeneration in humans and animals is associated with the modified tau protein in a manner typical of Alzheimer's disease neuropathology. Pathological changes in the tau protein, at the gene and protein level due to cerebral ischemia, can lead to the development of Alzheimer's disease-type neuropathology and dementia. Some studies have shown increased tau protein staining and gene expression in neurons following ischemia-reperfusion brain injury. Recent studies have found the tau protein to be associated with oxidative stress, apoptosis, autophagy, excitotoxicity, neuroinflammation, blood-brain barrier permeability, mitochondrial dysfunction, and impaired neuronal function. In this review, we discuss the interrelationship of these phenomena with post-ischemic changes in the tau protein in the brain. The tau protein may be at the intersection of many pathological mechanisms due to severe neuropathological changes in the brain following ischemia. The data indicate that an episode of cerebral ischemia activates the damage and death of neurons in the hippocampus in a tau protein-dependent manner, thus determining a novel and important mechanism for the survival and/or death of neuronal cells following ischemia. In this review, we update our understanding of proteomic and genomic changes in the tau protein in post-ischemic brain injury and present the relationship between the modified tau protein and post-ischemic neuropathology and present a positive correlation between the modified tau protein and a post-ischemic neuropathology that has characteristics of Alzheimer's disease-type neurodegeneration.


Altered mRNA expression of Pax5 and Blimp-1 in B cells in multiple myeloma.
Multiple myeloma (MM) is a plasma cell disorder that potentially initiates during an early stage of B-cell development. We encountered an unidentified isoform of B cell-specific activator protein (BSAP, or Pax5) in MM cells while performing differential analyses to compare mRNA expression in malignant and normal plasma cells. Pax5 is a transcription factor that plays a central role throughout B-cell development until the point of terminal differentiation. Our finding of this unique isoform prompted us to investigate Pax5 isoform usage in plasma cells and B-cell populations in other MM and healthy subjects. In contrast to normal Pax5 expression, we observed multiple isoforms of Pax5 in conjunction with low levels of expression of the full-length Pax5 in B cells from MM patients. The expressed isoforms in MM varied considerably from patient to patient, with no clear pattern. We also performed semiquantitative analyses of the mRNA expression levels of B lymphocyte-induced maturation protein (Blimp-1), because expression levels of Pax5 and Blimp-1 have been shown to be inversely correlated. We observed the expression of Blimp-1 in the B-cell populations in all 11 MM patients but in none of 11 healthy subjects. We hypothesize that premature Blimp-1 expression coupled to altered and deficient Pax5 expression causes some proliferating B cells to prematurely differentiate to plasma cells in MM.


Development and genetic differences of complement activity in rabbits.
The ontogeny of haemolytic complement in rabbit serum and the genetic differences of the activity in five strains of adult rabbits were investigated by single radial haemolysis in gel and a microtiter method with purified complement components and the appropriate haemolytic intermediate cells. The haemolytic complement activity was found as early as the 15th day of foetal life, and increased with age reaching approximately adult level by the 120th day of life. Marked strain differences in both total haemolytic activity and C3 levels of adult rabbit sera were observed. The repeatability of haemolytic activity for an individual serum taken at different times was higher than that for C3 level was observed. An inherited complement deficiency, due to the lack of C6, was found in a strain of Angora rabbits. The genetic studies confirmed that this complement defect was transmitted as an autosomal recessive trait.


Hypermethylation of BDNF and SST Genes in the Orbital Frontal Cortex of Older Individuals: A Putative Mechanism for Declining Gene Expression with Age.
Expression of brain-derived neurotrophic factor (BDNF) and somatostatin (SST) mRNAs in the brain decreases progressively and robustly with age, and lower BDNF and SST expression in the brain has been observed in many brain disorders. BDNF is known to regulate SST expression; however, the mechanisms underlying decreased expression of both genes are not understood. DNA methylation (DNAm) is an attractive candidate mechanism. To investigate the contribution of DNAm to the age-related decline in BDNF and SST expression, the Illumina Infinium HumanMethylation450 Beadchip Array was used to quantify DNAm of BDNF (26 CpG loci) and SST (9 CpG loci) in the orbital frontal cortices of postmortem brains from 22 younger (age <42 years) and 22 older individuals (age >60 years) with known age-dependent BDNF and SST expression differences. Relative to the younger individuals, 10 of the 26 CpG loci in BDNF and 8 of the 9 CpG loci in SST were significantly hypermethylated in the older individuals. DNAm in BDNF exons/promoters I, II, and IV negatively correlated with BDNF expression (r=-0.37, p<0.05; r=-0.40, p<0.05; r=-0.24, p=0.07), and DNAm in SST 5' UTR and first exon/intron negatively correlated with SST expression (r=-0.48, p<0.01; r=-0.63, p<0.001), respectively. An expanded set of BDNF- and GABA-related genes exhibited similar age-related changes in DNAm and correlation with gene expression. These results suggest that DNAm may be a proximal mechanism for decreased expression of BDNF, SST, and other BDNF- and GABA-related genes with brain aging and, by extension, for brain disorders in which their expression is decreased.


CT of the azygoesophageal recess in infants and children.
The contour of the azygoesophageal recess (AER) as seen with computed tomography (CT) is an important indicator of mediastinal disorders. Radiologists must recognize, however, that the AER contour varies with patient age. The configuration of the AER is dextroconvex in children younger than 6 years, nonconcave (ie, equally divided between convex and straight) in children aged 6-12 years, and concave (or adult-like) in adolescents and young adults (aged 12-20 years). The cause of this variation is not certain; however, chest wall configuration does not seem to be an important factor. Although a convex AER is normal and common in pediatric patients, this normal appearance must be distinguished from that of mediastinal abnormalities (eg, foregut malformation cysts, vascular anomalies, lymphadenopathy), which can also produce obvious or subtle convexity of the AER. An appreciation for the age-related variation in AER configuration helps in the interpretation of CT scans. Criteria such as attenuation, morphologic characteristics, cephalocaudal extent, and multicompartmental involvement may be helpful in the differential diagnosis, but, generally, mediastinal abnormalities that alter the AER are nonspecific in appearance.


A sport cream (Harpago-Boswellia-ginger-escin) for localized neck/shoulder pain.
Neck/shoulder, sudden pain, or muscular pain (not associated to structural or bone/joints components), due to fascial or muscular strain is common in active subjects, in non-professional athletes and sports performers. The aim of this supplement registry was the evaluation of a cream based on natural, active ingredients for topical application in supporting the improvement of pain and improving head/neck mobility, possibly minimizing the use of systemic drugs. The cream includes standardized active ingredients of natural origin as an extract of Harpagophytum procumbes, an extract from Boswellia serrata, a CO2 extract of ginger and escin. Subjects were divided into three groups, all using the standard management (SM) in combination with the Sport Cream or in addition to Flector (diclofenac) patch. The groups were comparable and homogeneous at the baseline. No side effects or skin tolerability issues were observed with the Sport Cream nor with the SM or diclofenac patches. Subjects receiving sport cream + SM reported a significant improvement in pain, stiffness, altered mobility and altered working capacity, with a reduced need for rescue medication (diclofenac) compared to subjects in the other two groups. Finally, subjects receiving sport cream + SM reported a more remarkable decrease in skin temperature in the affected area associated to an improvement in clinical symptoms.


The impact of the social context on the development of secondary hyperalgesia: an experimental study.
Social support has been shown to reduce pain ratings and physiological responses to acute pain stimuli. Furthermore, this relationship is moderated by adult attachment styles. However, these effects have not been characterized in experimentally induced symptoms of chronic pain, such as secondary hyperalgesia (SH) which is characterized by an increased sensitivity of the skin surrounding an injury. We aimed to examine whether social support by handholding from a romantic partner can attenuate the development of experimentally induced SH. Thirty-seven women, along with their partners, participated in 2 experimental sessions 1 week apart. In both sessions, SH was induced using an electrical stimulation protocol. In the support condition, the partner was seated across from the participant holding the participant's hand during the electrical stimulation, whereas in the alone condition, the participant went through the stimulation alone. Heart rate variability was measured for both the participant as well as the partner before, during, and after the stimulation. We found that the width of the area of hyperalgesia was significantly smaller in the support condition. Attachment styles did not moderate this effect of social support on the area width. Increasing attachment avoidance was associated with both a smaller width of hyperalgesia and a smaller increase in the sensitivity on the stimulated arm. For the first time, we show that social support can attenuate the development of secondary hyperalgesia and that attachment avoidance may be associated with an attenuated development of secondary hyperalgesia.


Exploring Mental Health and Substance use Treatment Needs of Commercially Sexually Exploited Youth Participating in a Specialty Juvenile Court.
The study sought to: (1) describe the mental health and substance use profiles among participants of a specialty trafficking court program (the Succeed Though Achievement and Resilience Court); (2) describe youths' mental health and substance use treatment prior to participating in the program; and (3) examine whether abuse influences report of mental health problems and/or substance use. Retrospective case review of court files was performed on commercially sexually exploited youth who volunteered to participate in the court from 2012 to 2014 (N = 184). All participants were female. Mental health problems and report of substance use was high among this population. Substance use differed at statistically significant levels between youth with a documented abuse history compared to those with no abuse history. Substance use also differed by report of mental health problems. Unexpected findings included the high rate of hospitalization for mental health problems and relatively low substance use treatment prior to STAR Court participation. Opportunities for improvement in critical points of contact to identify commercially sexually exploited youth and address their health needs are discussed.


Resistance to UV-induced cell-killing in nucleophosmin/B23 over-expressed NIH 3T3 fibroblasts: enhancement of DNA repair and up-regulation of PCNA in association with nucleophosmin/B23 over-expression.
Nucleophosmin/B23 was rapidly up-regulated after UV irradiation as p53, PCNA and c-Jun. UV induction of nucleophosmin/B23 was evidently increased at 3 h post-irradiation, and reached a maximum at 12 h, and remained high for at least 24 h. Over-expression of nucleophosmin/B23 made cells more resistant to UV-induced cell growth inhibition and death as compared with control vector-transfected cells through three main observations: cell growth/death percentage determination; clonogenic survival assay; and flow cytometric analysis. Moreover, nucleophosmin/B23 over-expressed cells had a greater capacity to repair UV-damaged reporter plasmid, indicating a higher nucleotide excision repair (NER) activity. Furthermore, PCNA, an essential component for DNA repair machinery, was correlated with nucleophosmin/B23 expression. Both protein level and promoter activity of PCNA were higher in nucleophosmin/B23 over-expressed cells than in control vector-transfected cells. On the other hand, treatment of cells with nucleophosmin/B23 antisense oligonucleotides decreased nucleophosmin/B23 and PCNA proteins, and potentiated the UV-induced cell killing. The effect of PCNA up-regulation may be one of the reasons that nucleophosmin/B23 over-expression made cells resistant to UV-induced growth inhibition and cell-killing.


Genetic evaluation of gestation length and its use in managing calving patterns.
Data collected from Australian Holstein cows that calved between 1995 and 2016 were used for estimating genetic parameters and genetic evaluation of gestation length (GL). Genetic parameters were estimated using a sire maternal grandsire model considering GL in heifers as correlated, but a different trait to adult cows and animal repeatability model. The key objective of this study was to assess if selective mating of bulls with short GL estimated breeding values (EBV) can help to modify calving patterns in predominantly pasture-based production systems and thereby contribute to the reduction of calving induction. The mean GL in heifers and adult cows was 280 and 281 d, respectively. The heritability of direct GL was 0.28 in heifers, which is slightly lower than in adult cows (0.36). The maternal heritability of GL was close to 0.04 in both heifer and adult cows. The genetic correlation between direct effects in heifers and adult cows was lower (0.88) than between maternal effects (0.94). A genetic evaluation model that considered heifer and adult cow data as the same trait in a repeatability animal model showed adequate variability in EBV for both direct and maternal GL. The genetic trend in direct GL EBV declined from 2005 in bulls and from 2006 in cows. Selective mating of bulls with short direct GL EBV showed that the GL and calving interval of their mates can be modified by up to 3.5 d for GL and 2.0 d for calving interval. Relative to parent average, the use of genotype data to calculate genomic EBV increased the reliability of EBV by up to 11% in validation bulls when daughter trait deviation of bulls with trait deviation of cows (11%) and deregressed breeding values (8%) were used as response variables. On average, for animals with only genotype data, the GL EBV can be predicted with about 50 to 60% reliability (expected) depending on the response variable (deregressed breeding values or daughter trait deviation and trait deviation) and the size of reference set. Overall, the results of this study show that calving patterns can be made tighter by selectively mating short GL EBV bulls to cows that do not become pregnant early in the mating season. Additionally, better reproductive management and the use of bulls with high female fertility EBV are still crucial for the success of a pasture-based dairy production system.


Dynamic fluctuations and spatial inhomogeneities in poly(N-isopropylacrylamide)/clay nanocomposite hydrogels studied by dynamic light scattering.
The contributions of the dynamic fluctuations and the frozen-in inhomogeneities to the total light scattering intensity observed in poly(N-isopropylacrylamide)/clay nanocomposite hydrogels were analyzed by applying the nonergodic method proposed by Pusey and van Megen. Approximately 90% of the total scattering intensity corresponds to the frozen-in component. The scattering intensity of the fluctuating component is smaller by far than that of a pure clay suspension, indicating that the thermal fluctuations of the clay particles are largely suppressed upon network formation. Accordingly, the fluctuating component consists of two contributions: one due to the polymer chains and the other, smaller one representing the residual mobility of the clay particles. The latter depends on how tightly the clay particles are fixed in the network. The dynamic features of the nanocomposite hydrogels are described by two relaxation modes. The fast one is purely diffusive and can be related to a dynamic correlation length of 6-8 nm, which is similar to that of a corresponding polymer solution. The relaxation time of the slow mode varies appreciably with sample position even though the data had been treated with the nonergodic method.


Competing models for the analysis of red cell survival obtained with 51Cr labelling technique.
A computer program for the analysis of 51Cr labelled red cell survival data was used in 84 patients and 8 normal subjects to estimate the parameters of 7 competing models derived from different hypotheses of the red cell destruction process. The purpose was to establish the optimal complexity of a red cell survival model to be used. Senescence or random destruction were the most common identified patterns of red cell death (79% of the cases). Models assuming different levels of death probability according to the age of cells, or 2 populations of cells with different death probabilities, were selected in 21% of the cases. These latter patients were characterized by the lowest values of MRCL. The conclusion of the work was that an automatic procedure for selecting the best model of red cell destruction is necessary when information concerning the mechanism of red cell death is required. For the more practical aim of obtaining an accurate measurement of the MRCL, the minimal set of competing models should account of at least 2 different populations of cells in addition to the random or senescence destruction models.


Effects of amrinone on the contractile behaviour of frog striated muscle fibres.
The effects of amrinone (0.005-2.1 mM) were studied on isolated single muscle fibres of the frog (0.6-4.3 degrees C). In the concentrations used amrinone potentiated the isometric twitch, increased the initial rate of force development and prolonged the time to peak twitch force and the time from peak force to half relaxation. There was a moderate but statistically significant (P less than 0.001) enhancement of the maximum tetanic force and a marked slowing of the relaxation phase of the tetanus. Amrinone depressed the velocity of unloaded shortening by 33 +/- 2% (mean +/- SE, n = 6) and reduced the curvature of the force-velocity relation leading to an increase of a/Po in Hill's (1938) hyperbolic equation. In accordance with the effects of amrinone on the force-velocity relation, there was a decrease in the rate of redevelopment of force after the fibre was released to zero tension during the tetanus plateau. The evidence suggests that the drug affects the contractile properties of frog muscle fibres by two different mechanisms: (I) amrinone affects the excitation-contraction coupling causing enhanced calcium release in response to membrane excitation and (2) amrinone exerts a direct effect on the kinetics of turnover of the myosin cross-bridges. The latter aspect of the drug effect was evaluated in terms of A.F. Huxley's (1957) cross-bridge model by means of a computer program.


Photoactive yellow protein-based protein labeling system with turn-on fluorescence intensity.
Protein labeling provides significant information about protein function. In this research, we developed a novel protein labeling technique by utilizing photoactive yellow protein (PYP). PYP is a small protein (14 kDa) derived from purple bacteria and binds to 7-hydroxycoumarin-3-carboxylic acid as well as to a natural ligand, 4-hydroxycinnamic acid, through a thioester bond with Cys69. Based on the structure and fluorescence property of this coumarin derivative, we designed two fluorescent probes that bind to PYP. One has an azido moiety, which allows stepwise labeling by click chemistry, and the other is a fluorogenic probe. The live-cell imaging and specific labeling of PYP were achieved by using both probes. The flexibility of the probe design and the small size of the tag protein are great advantages of this system against the existing methods. This novel labeling technique can be used in a wide variety of applications for biological research.


Effect of school feeding program on body mass index of primary school adolescents in Addis Ababa, Ethiopia: A prospective cohort study.
Governments and developmental organizations are encouraged to devote adequate resources to the establishment of free school meals to low-income children in developing countries. In Ethiopia, the school feeding program (SFP) is implemented in a few regions including the capital, Addis Ababa. However, the nutritional benefit of the program was not monitored and reported thus far. In this study, we evaluated the effect of the SFP on the body mass index (BMI) of primary school adolescents in Addis Ababa, Central Ethiopia. A prospective cohort study was employed to collect data from 644 SFP-beneficiary adolescents (n = 322) and non-SFP (n = 322). Nutritional outcomes were measured following 6 months of follow-up. WHO Anthroplus were used to convert anthropometric data into body-mass-index-for-age Z scores. The independent effect of school feeding is analyzed through a multivariable linear regression model. In linear regression, unadjusted model (Model 1), compared with the non-school-fed adolescents, the mean difference in difference of BAZ-score of school-fed adolescent was higher by 0.36 (β 0.36, 95% CI 0.17, 0.55). The beta coefficient remained positive after adjusted for age and sex (Model 2: β 0.35, 95% CI 0.16, 0.54) and sociodemographic variable (Model 3: β 0.35, 95% CI 0.16, 0.54). In the final model, adjusted for model four, lifestyle and health status there was a significant difference in favor of school-fed adolescents on BAZ-score indices (Model 4: β 0.4, 95% CI 0.18-0.62). On the contrary, for a unit increase in family size, the BAZ score will decrease by 0.06 (β 0.06, 95% CI -0.12--0.01). Similarly, adolescents with a middle tertile wealth index decreased their BAZ score by 0.30 (β 0.30, 95% CI -0.55--0.05) as compared to the higher tertile wealth index. School feeding was positively associated with a change in BAZ score whereas family size and middle tertile wealth index were negatively associated. This implies that school feeding can serve as an optimal strategy for addressing the nutrition needs of adolescents.


Targeting remaining pockets of malaria transmission in Kenya to hasten progress towards national elimination goals: an assessment of prevalence and risk factors in children from the Lake endemic region.
With an overall decline of malaria incidence, elimination of malaria is gradually becoming the next target for many of countries affected by the disease. In Kenya the national malaria control strategy is aiming to reach pre-elimination for most parts of the country. However, considerable heterogeneity in prevalence of the disease within the country and especially the remaining high prevalent region of the Lake endemic region is likely to slow progress towards this target. To achieve a sustained control and an eventual elimination, a clear understanding of drivers of ongoing malaria transmission in remaining hotspots is needed. Data from the 2015 Malaria Indicator Survey (MIS) were analysed for prevalence of malaria parasitaemia in children (6 months to 14 years) of different countries within the highly endemic Lake region. Univariate and multivariate logistic regression analysis were preformed to explore associations between selected risk factors and being parasitaemic. A predictive model was built for the association between malaria and the risk factors with the aim of identifying heterogeneities of the disease at the lower administrative levels. Overall, 604/2253 (27%, 95% CI 21.8-32.2) children were parasitaemic. The highest prevalence was observed in Busia County (37%) and lowest in Bungoma County (18%). Multivariate logistic regression analysis showed that the 10-14 years age group (OR = 3.0, 95% CI 2.3-4.1), households in the poorest socio-economic class (OR = 2.1, 95% CI 1.3-3.3), farming (OR = 1.4, 95% CI 1.2-2.5) and residence in Busia (OR = 4.6, 95% CI 2.1-8.2), Kakamega (OR = 2.6, 95% CI 1.3-5.4), and Migori counties (OR = 4.6 95% CI 2.1-10.3) were associated with higher risk of parasitaemia. Having slept under a long-lasting insecticide-treated bed net (LLIN) was associated with a lower risk (OR = 0.7, 95% CI 0.6-0.9). No association were found between malaria infection and the gender of the child, the household head, and the education status of the household head. Detailed analysis of malaria prevalence data in a hotspot area can identify new threats and avail opportunities for directing intervention. In the Lake endemic region of Kenya, interventions should be focused more on counties with the highest prevalence, and should target older children as well as children from the lower socio-economic strata. Precisely targeting interventions in remaining hotspots and high-risk populations will likely make impact and accelerate progress towards pre-elimination targets.


Bicycle safety. What's new in '92?
There are over 100 million bicycle riders in America, according to the National Safety Council, and in the last two years more than 1.25 million accidents have been reported. About 77% of these accidents occurred among children under 15 years old. Nearly 44% of reportable injuries were in the 5-14 year old age group and 30% occurred among children under five years of age, according to the National Center for Health Statistics.


The diagnostic accuracy of the 'classic meningeal signs' in children with suspected bacterial meningitis.
To prospectively determine the diagnostic accuracy of nuchal rigidity, Kernig's sign, and Brudzinski's sign in children with suspected bacterial meningitis. Children 3 months to 17 years old diagnosed with bacterial meningitis and matched controls without bacterial meningitis were enrolled. The diagnostic accuracy was calculated independently for each test and for a combinations of tests. Of 86 children, 40 (46.5%) had bacterial meningitis. The sensitivity, specificity, LR+, and LR- were 64.5%, 53.5%, 1.4, and 0.7 for nuchal rigidity, 52.6%, 77.5%, 2.3, and 0.6 for Brudzinski's sign, and 51.4%, 95.0%, 10.3, and 0.5 for Kernig's sign. The three tests did not yield any better results in the subsets of children with moderate or severe meningeal inflammation, nor in relation to any of the causative pathogens. In children with suspected meningitis, the three classic signs did not have a high diagnostic value and better bedside diagnostic signs are required.


A review of the genus Apristurus (Chondrichthyes: Carcharhiniformes: Scyliorhinidae) from Taiwanese waters.
Sharks of the genus Apristurus from Taiwanese waters are reviewed for the first time, and incorrect scientific names and wrong taxonomic information given in the literature are corrected. After extensive examination of specimens deposited in various museums, universities and fisheries institutions in Taiwan, Japan and China, the following five species are recognized from Taiwanese waters: Apristurus herklotsi (Fowler, 1934), A. longicephalus Nakaya, 1975, A. gibbosus Meng, Chu & Li, 1985, A. macrostomus Chu, Meng & Li, 1985, and A. platyrhynchus (Tanaka, 1909). Apristurus herklotsi, A. longicephalus, A. gibbosus and A. macrostomus are reported from Taiwanese waters for the first time, and the presence of A. platyrhynchus is formally recognized based on a single voucher specimen. Each species is fully described, and a key to the species of Apristurus in Taiwanese waters is provided. Morphological and biological information of each species is also provided.


Characterizing aggressive behavior with the Impulsive/Premeditated Aggression Scale among adolescents with conduct disorder.
This study extends the use of the Impulsive/Premeditated Aggression Scale for subtyping aggressive behavior among adolescents with Conduct Disorder. Of the Conduct Disorder symptoms, aggression has the strongest prognostic and treatment implications. While aggression is a complex construct, convergent evidence supports a dichotomy of impulsive and premeditated aggressive subtypes that are qualitatively different from one another in terms of phenomenology and neurobiology. Previous attempts at measuring subtypes of aggression in children and adults are not clearly generalizable to adolescents. Sixty-six adolescents completed a questionnaire for characterizing aggression (Impulsive/Premeditated Aggression Scale), along with standard measures of personality and general functioning. Principal components analysis demonstrated two stable factors of aggression with good internal consistency and construct validity. Compared to the premeditated aggression factor, the impulsive aggression factor was associated with a broader range of personality, thought, emotional, and social problems. As in the adult and child literature, characterization of aggressive behavior into two subtypes appears to be relevant to understanding individual differences among adolescents with Conduct Disorder.


Time on Therapy for at Least Three Months Correlates with Overall Survival in Metastatic Renal Cell Carcinoma.
With 15 drugs currently approved for the treatment of metastatic renal cell carcinoma (mRCC) and even more combination regimens with immunotherapy on the horizon, there remains a distinct lack of molecular biomarkers for therapeutic efficacy. Our study reports on real-world clinical outcomes of mRCC patients from a tertiary academic medical center treated with empirically selected standard-of-care therapy. We utilized the Stanford Renal Cell Carcinoma Database (RCCD) to report on various outcome measures, including overall survival (OS) and the median number of lines of targeted therapies received from the time of metastatic diagnosis. We found that most metastatic patients did not survive long enough to attempt even half of the available targeted therapies. We also noted that patients who failed to receive a clinical benefit within the first two lines of therapy could still go on to experience clinical benefit in later lines of therapy. The term, "clinical benefit" was assigned to a line of therapy if a patient remained on drug treatment for three months or longer. Moreover, patients with clinical benefit in at least one line of therapy experienced significantly longer OS compared to those who did not have clinical benefit in at least one line of therapy. Developing biomarkers that identify patients who will receive clinical benefit in individual lines of therapy is one potential strategy for achieving rational drug sequencing in mRCC.


Pathophysiological concepts of functional dyspepsia and irritable bowel syndrome future pharmacotherapy.
The functional gastrointestinal diseases (FGIDs) are often noticed disturbances. Functional dyspepsia (FD) is the most frequent FGID of the upper part of the gastrointestinal tract while irritable bowel syndrome (IBS) occurs in the lower gastrointestinal part. Both clinical entities are characterized by rich symptomatology and the pattern of the diagnostic guidelines. Recognition and the classification of FGIDs are difficult, consisting in exclusion of all possible organic disorders and subordinating on the predominant symptom basis to most appropriate class, acording to Rome III classification. The present FGIDs pharmacotherapy is limited mostly to the symptomatical treatment and it is based on medicines conventionally used in various gastrointestinal organic illnesses (antisecretory, gastroprotective agents, antidiarrhoeal and laxative drugs). Some of them which seem to diminish visceral hypersensitivity acting via serotonin receptors are also used, including 5-HT4 agonists and 5-HT3 antagonists. Many investigations over the new causal acting medicines last at present, which would be able to abolish the main pathophysiological FD and IBS mechanisms: visceral hypersensitivity and both myoelectrical and dysmotility phenomena. Thus, new pharmacological agents influencing opioid, purinergic, NMDA, CCK-A, or NK receptors are studied. The article is the mini-review, representing classification and the outline of the FGIDs pathogenesis, the present concepts of their pharmacological treatment and the future perspectives of pharmacoherapy with the use of new, interfering into key pathomechanisms drugs.


Duration but not intensity of alcohol and tobacco exposure predicts p16INK4A homozygous deletion in head and neck squamous cell carcinoma.
In tobacco-associated solid tumors, evidence suggests that the pattern of carcinogen exposure is related to the nature of somatic gene inactivation within crucial pathways, including the retinoblastoma (Rb) pathway. One somatic event in this pathway, homozygous deletion of the p16INK4A gene, is commonly observed in head and neck squamous cell carcinoma (HNSCC). Alcohol and tobacco are both well-established risk factors for HNSCC but there has been little characterization of the relationship of exposure to these carcinogens and inactivation of the p16INK4A gene. Hypothesizing that p16INK4A homozygous deletion is associated with tobacco and alcohol exposure, we investigated 330 consecutive HNSCC tumors. The odds ratio (OR) for p16INK4A homozygous deletion among alcohol consumers in the upper tertile (>43 years used) was 5.2 [95% confidence interval (95% CI), 2.1-12.8] as compared with those with < or = 43 years of alcohol consumption. Intensity of alcohol exposure, measured as average alcoholic drinks per week, was not associated with gene deletion. When we examined the distribution of duration of tobacco use, the OR for p16(INK4A) homozygous deletion was 1.3 (95% CI, 0.5-3.0) and 1.9 (95% CI, 0.9-4.0) for 29 to 39 years and >39 years of tobacco smoking, respectively, as compared with those that smoked < or = 28 years. As in the case of alcohol use, intensity of tobacco exposure (measured as packs per day) was not associated with gene deletion. Hence, the duration of alcohol use and duration of smoking, but not intensity of either, significantly predicted p16(INK4A) homozygous deletion in HNSCC.


Prevalence of Different Types of Primary Esophageal Motility Disorders and Their Associated Factors in Patients Referring to Shariati Hospital during 2018-2019.
BACKGROUND: Esophageal motility disorders (EMDs) are common in patients with dysphagia and are effectively diagnosed with high-resolution manometry (HREM). In this study, we aimed to evaluate the prevalence of different types of primary EMDs in patients referred for HREM and to further investigate the factors associated with EMDs. METHODS: In this cross-sectional study, all patients referred to the endoscopy section of Shariati Hospital during 2018-2019 (279 patients) were subjected to HREM and were evaluated according to their diagnosis, and the effect of each factor and each symptom on motility disorders was investigated. RESULTS: 84.5% (235) of the participants were diagnosed with at least one esophageal motility disorder; of them, achalasia was the most common form (52.6%). None of the predictive factors showed a statistically significant correlation with EMDs. However, regarding the symptoms, regurgitation and nocturnal cough were significantly more common in patients with EMD (P=0.001 and 0.009, respectively). CONCLUSION: This study demonstrates the high prevalence of EMDs in patients undergoing manometry. None of the factors studied, such as age, sex, diabetes, hypothyroidism, smoking, and alcohol and opium consumption, had a statistically significant correlation with EMDs.


Two canine Merkel cell tumours: immunoexpression of c-KIT, E-cadherin, beta-catenin and S100 protein.
Canine Merkel cell tumours are rare neuroendocrine neoplasms that show a relatively benign biological behaviour when compared with their human counterparts. To date, little information is available on their immunohistochemical properties. This report describes the histopathological and immunohistochemical features of two such tumours. The tumours' immunoreactivity profile was studied with respect to different cellular molecules including chromogranin A (CGA), neurone-specific enolase (NSE), S100 protein, c-KIT, the cytokeratins (CKs) detected by pancytokeratin (AE1/AE3) antibodies (i.e. high molecular weight CKs 1, 2, 3, 4, 5, 6, 10, 14, 15 and 16, and low molecular weight CKs 7, 8 and 19) and three markers proposed to correlate with increased malignancy in human tumours: E-cadherin, beta-catenin and p63 protein. In both lesions, tumour cells were positive for cytokeratins, CGA, NSE, S100 and c-KIT. No immunostaining was observed for p63 protein, and there was no loss or change in E-cadherin or beta-catenin immunoexpression. These results suggest that the generally benign behaviour of canine Merkel cell tumours, when compared with their human counterparts, may be partly explained by the conservation of important intercellular adhesion molecules such as E-cadherin and beta-catenin. Additionally, expression of S100 but not of the p63 protein suggests that these canine tumours present a trend towards neural, rather than basal, epithelial differentiation and do not readily compare with human Merkel cell tumours.


Uptake of Transanal Total Mesorectal Excision in North America: Initial Assessment of a Structured Training Program and the Experience of Delegate Surgeons.
Transanal total mesorectal excision is a new approach to curative-intent rectal cancer surgery. Training and surgeon experience with this approach has not been assessed previously in America. The purpose of this study was to characterize a structured training program and to determine the experience of delegate surgeons. Data were assimilated from an anonymous, online survey delivered to attendees on course completion. Data on surgeon performance during hands-on cadaveric dissection were collected prospectively. This study was conducted at a single tertiary colorectal surgery referral center, and cadaveric hands-on training was conducted at a specialized surgeon education center. The main outcome measurement was the use of the course and surgeon experience posttraining. During a 12-month period, eight 2-day transanal total mesorectal excision courses were conducted. Eighty-one colorectal surgeons successfully completed the course. During cadaveric dissection, 71% achieved a complete (Quirke 3) specimen; 26% were near complete (Quirke 2), and 3% were incomplete (Quirke 1). A total of 9.1% demonstrated dissection in the incorrect plane, whereas 4.5% created major injury to the rectum or surrounding structures, excluding the prostate. Thirty eight (46.9%) of 81 surgeon delegates responded to an online survey. Of survey respondents, 94.6% believed training should be required before performing transanal total mesorectal excision. Posttraining, 94.3% of surgeon delegates planned to use transanal total mesorectal excision for distal-third rectal cancers, 74.3% for middle-third cancers, and 8.6% for proximal-third cancers. The most significant complication reported was urethral injury; 5 were reported by the subset of survey respondents who had performed this operation postcourse. The study was limited by inherent reporting bias, including observer and recall biases. Although this structured training program for transanal total mesorectal excision was found to be useful by the majority of respondents, the risk of iatrogenic injury after training remains high, suggesting that this training pedagogy alone is insufficient. See Video Abstract at http://links.lww.com/DCR/A335.


Atrial Fibrillation in Athletes-Features of Development, Current Approaches to the Treatment, and Prevention of Complications.
Atrial fibrillation (AF) is one of the most common types of cardiac arrhythmias. This review article highlights the problem of the development of atrial fibrillation in individuals engaged in physical activity and sports. Predisposing factors, causes, and development mechanisms of atrial fibrillation in athletes from the perspective of the authors are described. Methods of treatment, as well as prevention of thromboembolic complications, are discussed. Directions for further studies of this problem and prevention of complications are proposed.


Monoclonal antibody study of the decorated spongiome of contractile vacuole complexes of Paramecium.
A monoclonal antibody (mAb) has been developed and selected by immunofluorescence for the radial canals of the contractile vacuole complex (CVC) of Paramecium multimicronucleatum. By applying indirect immunogold labeling to thin frozen sections this mAb has been shown at the electron microscopic level to be specific for the decorated spongiome. We have used the mAb to study the normal interfission appearance as well as developmental stages of the decorated spongiomes. Two decorated spongiomes, presumably involved in water sequestration, radiate as 5-10 bands from unlabeled, circular, 25 microns diameter centers. Two new CVCs arise just anterior to the space occupied by the old spongiomes, the new anterior CVC appearing slightly before the posterior one. Development of the new spongiomes around a 10 microns unlabeled central zone is accompanied by a regression of old spongiome bands until the lengths of these bands in both old and new CVCs are equal just before cell division. After division both old and new spongiome bands grow at equal rates to the same length. Exceptions to the above general scheme, both in number of CVCs in interfission, as well as in position of the new relative to the old CVCs, are also observed.


Genetic Similarity Assessment of Twin-Family Populations by Custom-Designed Genotyping Array.
Twin registries often take part in large collaborative projects and are major contributors to genome-wide association (GWA) meta-analysis studies. In this article, we describe genotyping of twin-family populations from Australia, the Midwestern USA (Avera Twin Register), the Netherlands (Netherlands Twin Register), as well as a sample of mothers of twins from Nigeria to assess the extent, if any, of genetic differences between them. Genotyping in all cohorts was done using a custom-designed Illumina Global Screening Array (GSA), optimized to improve imputation quality for population-specific GWA studies. We investigated the degree of genetic similarity between the populations using several measures of population variation with genotype data generated from the GSA. Visualization of principal component analysis (PCA) revealed that the Australian, Dutch and Midwestern American populations exhibit negligible interpopulation stratification when compared to each other, to a reference European population and to globally distant populations. Estimations of fixation indices (FST values) between the Australian, Midwestern American and Netherlands populations suggest minimal genetic differentiation compared to the estimates between each population and a genetically distinct cohort (i.e., samples from Nigeria genotyped on GSA). Thus, results from this study demonstrate that genotype data from the Australian, Dutch and Midwestern American twin-family populations can be reasonably combined for joint-genetic analysis.


Genome-Resolved Meta-Analysis of the Microbiome in Oil Reservoirs Worldwide.
Microorganisms inhabiting subsurface petroleum reservoirs are key players in biochemical transformations. The interactions of microbial communities in these environments are highly complex and still poorly understood. This work aimed to assess publicly available metagenomes from oil reservoirs and implement a robust pipeline of genome-resolved metagenomics to decipher metabolic and taxonomic profiles of petroleum reservoirs worldwide. Analysis of 301.2 Gb of metagenomic information derived from heavily flooded petroleum reservoirs in China and Alaska to non-flooded petroleum reservoirs in Brazil enabled us to reconstruct 148 metagenome-assembled genomes (MAGs) of high and medium quality. At the phylum level, 74% of MAGs belonged to bacteria and 26% to archaea. The profiles of these MAGs were related to the physicochemical parameters and recovery management applied. The analysis of the potential functional core in the reservoirs showed that the microbiota was specialized for each site, with 31.7% of the total KEGG orthologies annotated as functions (1690 genes) common to all oil fields, while 18% of the functions were site-specific, i.e., present only in one of the oil fields. The oil reservoirs with a lower level of intervention were the most similar to the potential functional core, while the oil fields with a long history of water injection had greater variation in functional profile. These results show how key microorganisms and their functions respond to the distinct physicochemical parameters and interventions of the oil field operations such as water injection and expand the knowledge of biogeochemical transformations in these ecosystems.


Comparison of superior vena cava and antecubital vein as DSA injection site.
A prospective study in 47 patients was undertaken to determine which of the two major sites for injection of contrast material, superior vena cava or antecubital vein, produces digital subtraction images of higher quality. Both injection sites were used to obtain images of the carotid and aortic arch areas in each patient. The two injection sites were also compared for ease of performance of the study, patient acceptance, and incidence of complications and motion artifacts. It was determined that the degree of vessel conspicuity is not affected by injection site when equal volumes of contrast material are injected. No significant differences in overall image quality attributable to injection site were found, except for carotid images obtained in the anteroposterior projection; for these images, the antecubital vein injection site produced significantly better images. Vessel conspicuity was not the major determinant of overall image quality as judged by radiologists.


Noncompliance with the WHO's Recommended Eight Antenatal Care Visits among Pregnant Women in Sub-Saharan Africa: A Multilevel Analysis.
In 2016, the World Health Organization (WHO) introduced a minimum of eight antenatal care (ANC) visits for positive pregnancy outcomes. This study examined the prevalence of noncompliance with 8+ ANCvisits and its associated factors in sub-Saharan Africa (SSA). We used data from the Demographic and Health Surveys of eight countries in SSA. A pooled sample of 63,266 pregnant women aged 15-49 years who had given birth to children within 5 years prior to the surveys was included in this study. To examine the factors associated with noncompliance with ANC 8+ visits, multilevel binary logistic regression analysis was conducted, and the results were reported using odds radios at 95% confidence interval (CI). The pooled prevalence of noncompliance with ANC 8+ visits was 92.3% (95% CI: 91.1%-93.3%) with the highest and lowest prevalence in Zambia (98.7%, 95% CI: 98.3%-99.1%) and Libya (73.4%, 95% CI: 70.4%-76.2%), respectively. With the individual level factors, women's age (44-49 years-aOR = 0.33, 9% CI: 0.14-0.78), health insurance registration, (yes-aOR = 0.53, 95% CI: 0.29-0.98), and economic status (richest-aOR = 0.16, 95% CI: 0.05-0.49) were negatively associated with noncompliance with 8+ ANC visits, while parity (five or more children-aOR = 1.68, 95% CI: 1.12-2.52) was positively associated with noncompliance with 8+ ANC visit. With the community level factors, community level literacy was negatively associated with noncompliance with 8+ ANC visit (high-aOR = 0.56, 95% CI: 0.32-0.99). About eight out of ten pregnant women did not comply with the WHO's recommended minimum of eight ANC visits for positive pregnancy outcomes in SSA. Empowering the economic status of women , enhancing health insurance and education coverage, and giving more attention to young pregnant women and those with more children are crucial for improving the coverage of ANC 8+ visits in the region.


Interactions between smoking, pulmonary surfactant protein B, and atherosclerosis in the general population: the Dallas Heart Study.
Pulmonary surfactant protein B (SP-B), an alveolar protein normally detectable at only very low concentrations in blood, circulates at higher levels among smokers and those with alveolar injury and inflammation. We hypothesized that SP-B may serve as a marker of the vascular effects of smoking and would thus be associated with subclinical measures of atherosclerosis. Plasma levels of SP-B were measured in 3294 subjects, ages 30 to 65, enrolled in the Dallas Heart Study, a probability-based population sample of Dallas County adults. Coronary artery calcium (CAC) was measured by computed tomography and abdominal aortic plaque (AP) by magnetic resonance imaging. The cohort comprised 29% current and 17% former smokers. The overall prevalence of CAC was 22%, and that of AP was 39%. Median SP-B levels were 5-fold higher among current versus never smokers (P<0.0001) and were significantly correlated with estimated pack-years smoked (Spearman ρ=0.35, P<0.0001). Increasing levels of SP-B also associated with other traditional cardiac risk factors and higher levels of inflammatory biomarkers. In univariable analyses, increasing SP-B quartiles associated with higher prevalence of both CAC and AP (P(trend)<0.0001 for each). In multivariable analyses adjusting for traditional cardiovascular risk factors, SP-B remained associated with AP (OR 1.87 for the 4th versus 1st quartiles, 95% confidence interval 1.39 to 2.51; P<0.0001) but not CAC. An interaction was observed between SP-B, smoking status, and AP (P(interaction)=0.01), such that SP-B associated with AP in current smokers (adjusted OR 2.15 for the 4th versus 1st quartile, 95% confidence interval 1.26 to 3.67; P=0.005) but not in former or never smokers. Circulating levels of SP-B increase with greater smoking burden and independently associate with abdominal AP among current smokers. Our findings support further investigation of the role of SP-B as a marker of the vascular effects of smoking.


Infantile hypophosphatasia: transplantation therapy trial using bone fragments and cultured osteoblasts.
Hypophosphatasia (HPP) is a rare, heritable, metabolic bone disease due to deficient activity of the tissue-nonspecific isoenzyme of alkaline phosphatase. The infantile form features severe rickets often causing death in the first year of life from respiratory complications. There is no established medical treatment. In 1997, an 8-month-old girl with worsening and life-threatening infantile HPP improved considerably after marrow cell transplantation. Our aim was to better understand and to advance these encouraging transplantation results. In 1999, based on emerging mouse transplantation models involving implanted donor bone fragments as well as osteoblast-like cells cultured from bone, we treated a 9-month-old girl suffering a similar course of infantile HPP. Four months later, radiographs demonstrated improved skeletal mineralization. Twenty months later, PCR analysis of adherent cells cultured from recipient bone suggested the presence of small amounts of paternal (donor) DNA despite the absence of hematopoietic engraftment. This patient, now 8 yr old (7 yr after transplantation), is active and growing, and has the clinical phenotype of the more mild, childhood form of HPP. Cumulative experience suggests that, after immune tolerance, donor bone fragments and marrow may provide precursor cells for distribution and engraftment in the skeletal microenvironment in HPP patients to form tissue-nonspecific isoenzyme of alkaline phosphatase-replete osteoblasts that can improve mineralization.


Ultrasound imaging for the rheumatologist XXXIII. Sonographic assessment of the foot in early arthritis patients.
To investigate the ability of ultrasonography (US) to detect synovitis in metatarsophalangeal joints (MTP) in patients with suspicion of early arthritis, and to discriminate between diagnoses. Patients referred to early arthritis clinics for differential diagnosis were enrolled, and clinical and laboratory measures were recorded. Ultrasonography of MTPs was performed searching for synovial hypertrophy (SH), joint effusion (JE) and power Doppler (PD), graded from 0 to 3 on a semi-quantitative scale. Patients were classified according to definite classification criteria, or as undifferentiated arthritis or non-inflammatory pathology. US findings were compared across different diagnoses and diagnostic accuracy was calculated taking clinical diagnosis as reference. Out of 427 patients (71% rheumatoid arthritis (RA), 20% undifferentiated arthritis (UA), 15% spondyloarthritides (SpA), 13% non-inflammatory), 307 (71.9%) showed SH, 120 (25.5%) JE, 77 (18.0%) PD. RA patients had median JE, SH and PD scores significantly higher than non-inflammatory and other diseases. Patient with UA and SpA had higher scores of SH and JE compared to non-inflammatory, no significant differences were present among different diagnosis. In RA, SH and JE were more frequently detected in the second MTP, and PD in the fifth. Crystal-related arthritis showed a tendency towards a more frequent involvement of the first MTP. The diagnostic accuracy of single US measures was moderate, but the detection of a PD of 2 or more provided a high specificity for the diagnosis of RA. US can be used as additional information in patients evaluated in an early arthritis setting. High scores of JE, SH and PD, together with the pattern of involvement are suggestive of RA.


The growing vaccine hesitancy: exploring the influence of the internet.
Vaccination coverage is dropping in several countries, including Slovenia. More and more people hesitate or even reject vaccinations. As the influence of the internet grows, the question becomes how to communicate about vaccination to parents in order to prevent this drop in vaccination coverage among children. For the first time in Europe, the Situational Theory of Publics (STOP) has been used in the field of vaccination to segment mothers to subpublics, and to prescribe a clearly defined form of communication for each of the segmented groups. In the survey, 1704 mothers participated who gave birth in 2014 and 2015 in Slovenia. The study showed that mothers react passively to information on vaccination no matter whether they come across it coincidentally or intentionally. Most often, they seek information about vaccination from friends or online. The more concerned they are about the safety of vaccines, the more they search for information about vaccination, and their communication is consequently more active. The mothers that problematize the safety of vaccines more, and are afraid of their adverse events tend to be in favour of alternative options. Our research demonstrated that the STOP can be applied to the field of vaccination. There is a huge need for intensive professional communication about vaccination on the internet and social media. The improvement of the communicational competences of doctors and healthcare workers is essential to achieve better communication with parents and the media, and needs to be focused on mothers and pregnant women.