Methylation profiling in acute myeloid leukemia.
Aberrant methylation of multiple CpG islands has been described in acute myeloid leukemia (AML), but it is not known whether these are independent events or whether they reflect specific methylation defects in a subset of cases. To study this issue, the methylation status of 14 promoter-associated CpG islands was analyzed in 36 cases of AML previously characterized for estrogen-receptor methylation (ERM). Cases with methylation density of 10% or greater were considered positive. Seventeen cases (47%) were ERM(+) while 19 cases were ERM(-). Hypermethylation of any of the following, p15, p16, CACNA1G, MINT1, MINT2, MDR1, THBS1, and PTC1 (2 promoters), was relatively infrequent (6% to 31% of patients). For each of these CpG islands, the methylation density was positively correlated with ERM density (rank order correlation coefficients, 0.32-0.59; 2-tailed P < or = .058 for each gene). Hypermethylation of MYOD1, PITX2, GPR37, and SDC4 was frequently found in AML (47% to 64% of patients). For each of these genes as well, methylation density was positively correlated with ERM density (correlation coefficients 0.43 to 0.69, P < or = .0087 for each gene). MLH1 was unmethylated in all cases. Hypermethylation of p15, MDR1, and SDC4 correlated with reduced levels of expression. There was an inverse correlation between age and the number of genes methylated (P = .0030). It was concluded that CpG-island methylation in AML results from methylation defects in subsets of cases. These results have potential implications for the classification and prognosis of AML and for the identification of patients who may benefit from treatment with methylation inhibitors.


An architecture for the automatic acquisition of vital signs by clinical information systems.
An architecture is presented which provides clinical information systems with access to vital sign information from medical devices. Middleware components encapsulate details of communicating with devices whilst adoption of de facto and international standards maximizes interoperability with client software. An application in routine clinical use is described.


Novel agents in gastroenteropancreatic neuroendocrine tumors.
Neuroendocrine tumors (NET) are a diverse group of tumors that derive from epithelial cells with neuroendocrine differentiation. Gastroenteropancreatic neuroendocrine tumors are a subset of NET that arises in the gastrointestinal tract. Clinical symptoms and presentations vary depending on the location and hormones produced by the tumor. Treatment of advanced and metastatic gastroenteropancreatic NETs has traditionally been difficult with few systemic treatment options. In 2011, two new targeted therapies, everolimus and sunitinib were approved for treatment of pancreatic NET leading to increased interest in novel agents active in gastroenteropancreatic NETs. At the 2013 ASCO Gastrointestinal Cancers Symposium two abstracts presented new data regarding novel therapies. Lombard-Bohas et al. (Abstract #224) presented new data from the RADIANT-3 trial and Shen et al. (Abstract #322) looked at the use of octreotide in elderly patients with carcinoid syndrome.


Arhgef5 Binds α-Dystrobrevin 1 and Regulates Neuromuscular Junction Integrity.
The neuromuscular junctions (NMJs) connect muscle fibers with motor neurons and enable the coordinated contraction of skeletal muscles. The dystrophin-associated glycoprotein complex (DGC) is an essential component of the postsynaptic machinery of the NMJ and is important for the maintenance of NMJ structural integrity. To identify novel proteins that are important for NMJ organization, we performed a mass spectrometry-based screen for interactors of α-dystrobrevin 1 (aDB1), one of the components of the DGC. The guanidine nucleotide exchange factor (GEF) Arhgef5 was found to be one of the aDB1 binding partners that is recruited to Tyr-713 in a phospho-dependent manner. We show here that Arhgef5 localizes to the NMJ and that its genetic depletion in the muscle causes the fragmentation of the synapses in conditional knockout mice. Arhgef5 loss in vivo is associated with a reduction in the levels of active GTP-bound RhoA and Cdc42 GTPases, highlighting the importance of actin dynamics regulation for the maintenance of NMJ integrity.


Lipoprotein(a) is not associated with venous thromboembolism risk.
Objectives. Evidence from case-control studies as well as meta-analyses of these study designs suggest elevated lipoprotein(a) [Lp(a)] to be associated with an increased risk of venous thromboembolism (VTE). Prospective evidence on the association is limited, uncertain, and could be attributed to regression dilution bias. We aimed to assess the prospective association of Lp(a) with risk of VTE and correct for regression dilution. Design. We related plasma Lp(a) concentrations to the incidence of VTE in 2,180 men of the Kuopio Ischemic Heart Disease cohort study. Hazard ratios (HRs) (95% confidence intervals [CI]) were assessed and repeat measurements of Lp(a) at 4 and 11 years from baseline, were used to correct for within-person variability. Results. After a median follow-up of 24.9 years, 110 validated VTE cases were recorded. The regression dilution ratio of loge Lp(a) adjusted for age was 0.85 (95% CI: 0.82-0.89). In analyses adjusted for several established risk factors and potential confounders, the HR (95% CI) for VTE per 1 SD (equivalent to 3.56-fold) higher baseline loge Lp(a) was 1.06 (0.87-1.30). In pooled analysis of five population-based cohort studies (including the current study) comprising 66,583 participants and 1314 VTE cases, the fully-adjusted corresponding HR for VTE was 1.00 (95% CI: 0.94-1.07), with no evidence of heterogeneity between studies. Conclusions. Primary analysis as well as pooled evidence from previous studies suggest circulating Lp(a) is not prospectively associated with future VTE risk, indicating that evidence of associations demonstrated in case-control designs may be driven by biases such as selection bias.


Top predators negate the effect of mesopredators on prey physiology.
Predation theory and empirical evidence suggest that top predators benefit the survival of resource prey through the suppression of mesopredators. However, whether such behavioural suppression can also affect the physiology of resource prey has yet to be examined. Using a three-tier reef fish food web and intermittent-flow respirometry, our study examined changes in the metabolic rate of resource prey exposed to combinations of mesopredator and top predator cues. Under experimental conditions, the mesopredator (dottyback, Pseudochromis fuscus) continuously foraged and attacked resource prey (juveniles of the damselfish Pomacentrus amboinensis) triggering an increase in prey O2 uptake by 38 ± 12·9% (mean ± SE). The visual stimulus of a top predator (coral trout, Plectropomus leopardus) restricted the foraging activity of the mesopredator, indirectly allowing resource prey to minimize stress and maintain routine O2 uptake. Although not as strong as the effect of the top predator, the sight of a large non-predator species (thicklip wrasse, Hemigymnus melapterus) also reduced the impact of the mesopredator on prey metabolic rate. We conclude that lower trophic-level species can benefit physiologically from the presence of top predators through the behavioural suppression that top predators impose on mesopredators. By minimizing the energy spent on mesopredator avoidance and the associated stress response to mesopredator attacks, prey may be able to invest more energy in foraging and growth, highlighting the importance of the indirect, non-consumptive effects of top predators in marine food webs.


Bioavailability of lysine for kittens in overheated casein is underestimated by the rat growth assay method.
Growth assays were performed to determine lysine bioavailability for kittens and rats in untreated and heated casein; these values were compared with estimates obtained with an in vitro method. Body weight, food intake, nitrogen and dry matter digestibility, and plasma lysine were determined during an 80-day growth trial using kittens (n = 16). Body weight and food intake were determined during a 21-day growth trial using weanling rats (n = 80). The growth data showed bioavailable lysine to be 102.4% and 100.2% (for untreated casein) and 66.1% and 51.7% (for heated casein) for kittens and rats, respectively. There was no relationship between plasma lysine and dietary lysine concentrations for kittens. There were no significant differences in nitrogen or dry matter digestibility among diets for kittens. The chemically reactive lysine content of untreated casein was 99.6%, and of heated casein was 67.1%. Heat treatment of casein resulted in significantly decreased lysine bioavailability as estimated by all methods. For untreated casein, both growth assays showed good agreement with the in vitro method for available lysine. For heated casein, the rat growth assay significantly underestimated bioavailable lysine as determined in kittens while the in vitro method closely approximated this value for the cat.


A discrete in continuous mathematical model of cardiac progenitor cells formation and growth as spheroid clusters (Cardiospheres).
We propose a discrete in continuous mathematical model describing the in vitro growth process of biophsy-derived mammalian cardiac progenitor cells growing as clusters in the form of spheres (Cardiospheres). The approach is hybrid: discrete at cellular scale and continuous at molecular level. In the present model, cells are subject to the self-organizing collective dynamics mechanism and, additionally, they can proliferate and differentiate, also depending on stochastic processes. The two latter processes are triggered and regulated by chemical signals present in the environment. Numerical simulations show the structure and the development of the clustered progenitors and are in a good agreement with the results obtained from in vitro experiments.


Concordance between upper and lower airway microbiota in infants with cystic fibrosis.
Nasopharyngeal and oropharyngeal samples are commonly used to direct therapy for lower respiratory tract infections in non-expectorating infants with cystic fibrosis (CF).We aimed to investigate the concordance between the bacterial community compositions of 25 sets of nasopharyngeal, oropharyngeal and bronchoalveolar lavage (BAL) samples from 17 infants with CF aged ∼5 months (n=13) and ∼12 months (n=12) using conventional culturing and 16S-rRNA sequencing.Clustering analyses demonstrated that BAL microbiota profiles were in general characterised by a mixture of oral and nasopharyngeal bacteria, including commensals like Streptococcus, Neisseria, Veillonella and Rothia spp. and potential pathogens like Staphylococcus aureus, Haemophilus influenzae and Moraxella spp. Within each individual, however, the degree of concordance differed between microbiota of both upper respiratory tract niches and the corresponding BAL.The inconsistent intra-individual concordance between microbiota of the upper and lower respiratory niches suggests that the lungs of infants with CF may have their own microbiome that seems seeded by, but is not identical to, the upper respiratory tract microbiome.


Extracorporeal membrane oxygenation as rescue therapy for severe hypoxemic respiratory failure.
Extracorporeal membrane oxygenation (ECMO) has been used for more than 50 years as salvage therapy for patients with severe cardiopulmonary failure refractory to conventional treatment. ECMO was first used in the 1960s to treat hypoxemic respiratory failure in newborns. On the basis of its success in that population, ECMO began to be used in the early 1970s to treat adult hypoxemic respiratory failure. However, outcomes for adults were, somewhat perplexingly, quite poor. By the 1980s, use of ECMO for severe hypoxemia was rare outside of the pediatric population. ECMO technology, however, continued to evolve and improve. Multiple case reports and small series describing ECMO use as rescue for adults with severe hypoxemia from various lung pathologies have appeared in the literature over the past three decades. Adult respiratory distress syndrome (ARDS) is often the final common pathway of various pathologies affecting adults and causing hypoxemic respiratory failure. It is prevalent in intensive care units throughout the world and has, since it was first described in 1967, carried a high mortality. No specific therapy for ARDS has been found, and current care is supportive, primarily by mechanical ventilation. Results from recent randomized controlled trials, however, suggest that ECMO may have a place in the treatment of these patients. This article reviews these studies and recommends adding severe ARDS to the list of established indications for ECMO in patients with hypoxemic respiratory failure.


Dissecting the machinery that introduces disulfide bonds in Pseudomonas aeruginosa.
Disulfide bond formation is required for the folding of many bacterial virulence factors. However, whereas the Escherichia coli disulfide bond-forming system is well characterized, not much is known on the pathways that oxidatively fold proteins in pathogenic bacteria. Here, we report the detailed unraveling of the pathway that introduces disulfide bonds in the periplasm of the human pathogen Pseudomonas aeruginosa. The genome of P. aeruginosa uniquely encodes two DsbA proteins (P. aeruginosa DsbA1 [PaDsbA1] and PaDsbA2) and two DsbB proteins (PaDsbB1 and PaDsbB2). We found that PaDsbA1, the primary donor of disulfide bonds to secreted proteins, is maintained oxidized in vivo by both PaDsbB1 and PaDsbB2. In vitro reconstitution of the pathway confirms that both PaDsbB1 and PaDsbB2 shuttle electrons from PaDsbA1 to membrane-bound quinones. Accordingly, deletion of both P. aeruginosa dsbB1 (PadsbB1) and PadsbB2 is required to prevent the folding of several P. aeruginosa virulence factors and to lead to a significant decrease in pathogenicity. Using a high-throughput proteomic approach, we also analyzed the impact of PadsbA1 deletion on the global periplasmic proteome of P. aeruginosa, which allowed us to identify more than 20 new potential substrates of this major oxidoreductase. Finally, we report the biochemical and structural characterization of PaDsbA2, a highly oxidizing oxidoreductase, which seems to be expressed under specific conditions. By fully dissecting the machinery that introduces disulfide bonds in P. aeruginosa, our work opens the way to the design of novel antibacterial molecules able to disarm this pathogen by preventing the proper assembly of its arsenal of virulence factors. The human pathogen Pseudomonas aeruginosa causes life-threatening infections in immunodepressed and cystic fibrosis patients. The emergence of P. aeruginosa strains resistant to all of the available antibacterial agents calls for the urgent development of new antibiotics active against this bacterium. The pathogenic power of P. aeruginosa is mediated by an arsenal of extracellular virulence factors, most of which are stabilized by disulfide bonds. Thus, targeting the machinery that introduces disulfide bonds appears to be a promising strategy to combat P. aeruginosa. Here, we unraveled the oxidative protein folding system of P. aeruginosa in full detail. The system uniquely consists of two membrane proteins that generate disulfide bonds de novo to deliver them to P. aeruginosa DsbA1 (PaDsbA1), a soluble oxidoreductase. PaDsbA1 in turn donates disulfide bonds to secreted proteins, including virulence factors. Disruption of the disulfide bond formation machinery dramatically decreases P. aeruginosa virulence, confirming that disulfide formation systems are valid targets for the design of antimicrobial drugs.


PKCε phosphorylation of the sodium channel NaV1.8 increases channel function and produces mechanical hyperalgesia in mice.
Mechanical hyperalgesia is a common and potentially disabling complication of many inflammatory and neuropathic conditions. Activation of the enzyme PKCε in primary afferent nociceptors is a major mechanism that underlies mechanical hyperalgesia, but the PKCε substrates involved downstream are not known. Here, we report that in a proteomic screen we identified the NaV1.8 sodium channel, which is selectively expressed in nociceptors, as a PKCε substrate. PKCε-mediated phosphorylation increased NaV1.8 currents, lowered the threshold voltage for activation, and produced a depolarizing shift in inactivation in wild-type - but not in PKCε-null - sensory neurons. PKCε phosphorylated NaV1.8 at S1452, and alanine substitution at this site blocked PKCε modulation of channel properties. Moreover, a specific PKCε activator peptide, ψεRACK, produced mechanical hyperalgesia in wild-type mice but not in Scn10a-/- mice, which lack NaV1.8 channels. These studies demonstrate that NaV1.8 is an important, direct substrate of PKCε that mediates PKCε-dependent mechanical hyperalgesia.


Serum biomarkers to evaluate the integrity of the neurovascular unit.
Biomarkers have the potential to enable the clinicians to screen infants for brain injury, monitor progression of disease, identify injured brain regions, assess efficacy of neuroprotective therapies, and offer hope to identify the timing of the injury, thus shedding light on the potential pathophysiology and the most effective therapy. Currently, clinicians do not routinely use biomarkers to care for neonates with Neonatal Encephalopathy (NE) and brain injury due to prenatal hypoxia-asphyxia. This review will cover potential biomarkers of the neurovascular unit in the setting of NE that (i) can help assess the degree or severity of encephalopathy at birth; (ii) can help monitor progression of disease process and efficacy of neuroprotective therapy; (iii) can help assess neurodevelopmental outcome. These biomarkers will be summarized in two categories: 1) Specific biomarkers targeting the neurovascular unit such as glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), S100B, and neuron specific enolase (NSE) and 2) general inflammatory cytokines, such as interleukin-6 (IL-6), interleukin-1b (IL-1b), and pNF-H, among others.


[Representations of informal jobs and health risks among housemaids and construction workers].
During the past few decades, the Brazilian labor market has been characterized by an increase of unregistered workers, earning lower wages, not covered by social insurance or occupational risk prevention programs. This study describes the representations and perceptions about informal work contracts and job-related health risks, analyzed in a group of injured unregistered workers. This was a qualitative study based on in-depth interviews carried out with seventeen laborers, nine housemaids and eight construction workers. The findings indicate that workers recognize the importance of formal jobs, mainly because of legal guarantees of labor rights, mentioning the symbolic downgrading of informal jobs that undermines their self-esteem. Both work groups tended to minimize occupational health risks in the work environment, and did not recognize associations between informal job contracts and occupational accidents or diseases. It was clear that workers want to have job contracts. The findings of the study demonstrate the need for broader dissemination and discussion about labor rights and the construction of public policies that encompass health and safety programs for these workers.


Efficacy and safety of terbinafine hydrochloride 1% cream vs eberconazole nitrate 1% cream in localised tinea corporis and tinea cruris.
To study and compare the efficacy and safety of topical terbinafine hydrochloride 1% cream and eberconazole nitrate 1% cream in localized tinea corporis and cruris. Patients were randomized after considering various inclusion and exclusion criteria into two groups. Group A (treated with terbinafine 1% cream for 3 weeks) and group B (treated with eberconazole 1% cream for 3 weeks). The sample size was of 30 patients with 15 patients in each group. Assessment of clinical improvement, KOH mount and culture was done weekly up to 3 weeks to assess complete cure. On comparison between the two groups, it was observed that eberconazole nitrate 1% cream was as effective as terbinafine hydrochloride 1% cream at the end of first (Non-sisgnificant (NS); P = 0.608, 1.00), second (NS; P = 0.291,0.55), and third (P = 1.00, 1.00) weeks with statistically nonsignificant clinical and mycological values. In both the groups, clinically no significant local side effects were noticed. The newer fungistatic eberconazole nitrate 1% cream was as effective as the fungicidal terbinafine hydrochloride 1% cream. Both the drugs showed good tolerability with no adverse effects.


Cell cycle-dependent phosphorylation of Theileria annulata schizont surface proteins.
The invasion of Theileria sporozoites into bovine leukocytes is rapidly followed by the destruction of the surrounding host cell membrane, allowing the parasite to establish its niche within the host cell cytoplasm. Theileria infection induces host cell transformation, characterised by increased host cell proliferation and invasiveness, and the activation of anti-apoptotic genes. This process is strictly dependent on the presence of a viable parasite. Several host cell kinases, including PI3-K, JNK, CK2 and Src-family kinases, are constitutively activated in Theileria-infected cells and contribute to the transformed phenotype. Although a number of host cell molecules, including IkB kinase and polo-like kinase 1 (Plk1), are recruited to the schizont surface, very little is known about the schizont molecules involved in host-parasite interactions. In this study we used immunofluorescence to detect phosphorylated threonine (p-Thr), serine (p-Ser) and threonine-proline (p-Thr-Pro) epitopes on the schizont during host cell cycle progression, revealing extensive schizont phosphorylation during host cell interphase. Furthermore, we established a quick protocol to isolate schizonts from infected macrophages following synchronisation in S-phase or mitosis, and used mass spectrometry to detect phosphorylated schizont proteins. In total, 65 phosphorylated Theileria proteins were detected, 15 of which are potentially secreted or expressed on the surface of the schizont and thus may be targets for host cell kinases. In particular, we describe the cell cycle-dependent phosphorylation of two T. annulata surface proteins, TaSP and p104, both of which are highly phosphorylated during host cell S-phase. TaSP and p104 are involved in mediating interactions between the parasite and the host cell cytoskeleton, which is crucial for the persistence of the parasite within the dividing host cell and the maintenance of the transformed state.


Gene structure, expression and chromosomal localization of murine theta class glutathione transferase mGSTT1-1.
We have isolated and characterized a cDNA and partial gene encoding a murine subfamily 1 Theta class glutathione transferase (GST). The cDNA derived from mouse GSTT1 has an open reading frame of 720 bp encoding a peptide of 240 amino acids with a calculated molecular mass of 27356 Da. The encoded protein shares only 51% deduced amino acid sequence identity with mouse GSTT2, but greater than 80% deduced amino acid sequence identity with rat GSTT1 and human GSTT1. Mouse GSTT1-1 was expressed in Escherichia coli as an N-terminal 6x histidine-tagged protein and purified using immobilized-metal affinity chromatography on nickel-agarose. The yield of the purified recombinant protein from E. coli cultures was approx. 14 mg/l. Recombinant mouse GSTT1-1 was catalytically active towards 1, 2-epoxy-3-(p-nitrophenoxy)propane, 4-nitrobenzyl chloride and dichloromethane. Low activity towards 1-menaphthyl sulphate and 1-chloro-2,4-dinitrobenzene was detected, whereas mouse GSTT1-1 was inactive towards ethacrynic acid. Recombinant mouse GSTT1-1 exhibited glutathione peroxidase activity towards cumene hydroperoxide and t-butyl hydroperoxide, but was inactive towards a range of secondary lipid-peroxidation products, such as the trans-alk-2-enals and trans,trans-alka-2,4-dienals. Mouse GSTT1 mRNA is most abundant in mouse liver and kidney, with some expression in intestinal mucosa. Mouse GSTT1 mRNA is induced in liver by phenobarbital, but not by butylated hydroxyanisole, beta-napthoflavone or isosafrole. The structure of mouse GSTT1 is conserved with that of the subfamily 2 Theta class GST genes mouse GSTT2 and rat GSTT2, comprising five exons interrupted by four introns. The mouse GSTT1 gene was found, by in situ hybridization, to be clustered with mouse GSTT2 on chromosome 10 at bands B5-C1. This region is syntenic with the location of the human Theta class GSTs clustered on chromosome 22q11.2. Similarity searches of a mouse-expressed sequence tag database suggest that there may be two additional members of the Theta class that share 70% and 88% protein sequence identity with mouse GSTT1, but less than 55% sequence identity with mouse GSTT2.


Dietary medium-chain fatty acids and risk of incident colorectal cancer in a predominantly low-income population: a report from the Southern Community Cohort Study.
No prospective observational study has specifically examined the associations between dietary intakes of medium-chain fatty acids and risk of colorectal cancer. This study examined the association between dietary intakes of medium-chain fatty acids and colorectal cancer risk overall and by racial subgroups in a predominantly low-income United States population. This prospective study included 71,599 eligible participants aged 40 to 79 who were enrolled in the Southern Community Cohort Study between 2002 and 2009 in 12 southeastern United States states. Incident colorectal cancer cases were ascertained via linkage to state cancer registries, which was completed through 31 December, 2016. The dietary intakes of medium-chain fatty acids were assessed using a validated 89-item food frequency questionnaire. Multivariable Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between intakes of medium-chain fatty acids and risk for incident colorectal cancer. Among 71,599 participants, 48,008 (67.3%) were Black individuals and 42,260 (59.0%) were female. A total of 868 incident colorectal cancer cases occurred during a median follow-up of 13.7 y. Comparing the highest to the lowest quartile, high intake of dodecanoic acid/lauric acid (C12:0) was associated with reduced risk of colorectal cancer among White participants (HR: 0.52; 95% CI: 0.30, 0.91; P-trend = 0.05), but not in Black individuals (HR: 0.92; 95% CI, 0.68, 1.24; P-trend = 0.80) in multivariable-adjusted models. No associations were found between intakes of hexanoic acid/caproic acid (C6:0), octanoic acid/caprylic acid (C8:0), or decanoic acid/capric acid (C10:0) and risk of incident colorectal cancer overall or within racial subgroups. In a predominantly low-income United States population, an increased dietary C12:0 intake was associated with a substantially reduced risk of colorectal cancer only among White individuals, but not in Black individuals.


Antimicrobial edible films and coatings for meat and meat products preservation.
Animal origin foods are widely distributed and consumed around the world due to their high nutrients availability but may also provide a suitable environment for growth of pathogenic and spoilage microorganisms. Nowadays consumers demand high quality food with an extended shelf life without chemical additives. Edible films and coatings (EFC) added with natural antimicrobials are a promising preservation technology for raw and processed meats because they provide good barrier against spoilage and pathogenic microorganisms. This review gathers updated research reported over the last ten years related to antimicrobial EFC applied to meat and meat products. In addition, the films gas barrier properties contribute to extended shelf life because physicochemical changes, such as color, texture, and moisture, may be significantly minimized. The effectiveness showed by different types of antimicrobial EFC depends on meat source, polymer used, film barrier properties, target microorganism, antimicrobial substance properties, and storage conditions. The perspective of this technology includes tailoring of coating procedures to meet industry requirements and shelf life increase of meat and meat products to ensure quality and safety without changes in sensory characteristics.


[Carcinoma of the Fallopian tube: a case].
The case of a 43-years old woman with previous history of mental retardation and major depressive syndrome, consulting for metrorrhagia is presented. At physical examination a right adnexal mass was detected on palpation. Transvaginal echography showed a 3-cavity cyst in right ovary. A surgical intervention with total hysterectomy and dual adnexectomy was performed. Pathological study showed proliferative endometrium, bilateral follicular cysts and well differentiated serous adenocarcinoma located at fallopian tube. The patient refused adjuvant chemotherapy, a close follow-up is ongoing in outpatient Oncology Unit. Then some epidemiologic, etiologic, clinica, diagnostic and therapeutic issues related to this rare tumour are discussed.


Assessment of benign tumor burden by whole-body MRI in patients with neurofibromatosis 1.
People with neurofibromatosis 1 (NF1) have multiple benign neurofibromas and a 10% lifetime risk of developing malignant peripheral nerve sheath tumors (MPNSTs). Most MPNSTs develop from benign plexiform neurofibromas, so the burden of benign tumors may be a risk factor for developing MPNST. We studied 13 NF1 patients with MPNSTs and 26 age- and sex-matched controls (NF1 patients who did not have MPNSTs) with detailed clinical examinations and whole-body MRI to characterize their body burden of internal benign neurofibromas. Internal plexiform neurofibromas were identified in 22 (56%) of the 39 NF1 patients studied. All six of the NF1 patients with MPNSTs under 30 years of age had neurofibromas visualized on whole-body MRI, compared to only 3 of 11 matched NF1 controls under age 30 (p < 0.05). Both the median number of plexiform neurofibromas (p < 0.05) and the median neurofibroma volume (p < 0.01) on whole-body MRI were significantly greater among MPNST patients younger than 30 years of age than among controls. No significant differences in whole-body MRI findings were observed between NF1 patients with MPNSTs and controls who were 30 years of age or older. Whole-body MRI of NF1 patients allows assessment of the burden of internal neurofibromas, most of which are not apparent on physical examination. Whole-body imaging of young NF1 patients may allow those at highest risk for developing MPNST to be identified early in life. Close surveillance of these high-risk patients may permit earlier diagnosis and more effective treatment of MPNSTs that develop.


Circular RNAs in pancreatic cancer progression.
Pancreatic cancer (PC), typically diagnosed at relatively advanced stages with poor prognosis, is a dominant cause of cancer-related deaths worldwide. Accumulating evidence demonstrates that circular RNAs (circRNAs) are abnormally expressed in diverse tumors and affect tumorigenesis and progression. In this article, we examine the roles of circRNAs in regulation of PC progression. Additionally, circRNAs enriched in exosomes could be transferred among PC cells to modulate malignancy. Characterization of regulatory mechanisms involving circRNAs in general and PC specifically will enable earlier detection and potential development of therapeutic strategies.


Amendment of arsenic and chromium polluted soil from wood preservation by iron residues from water treatment.
An iron-rich water treatment residue (WTR) consisting mainly of ferrihydrite was used for immobilization of arsenic and chromium in a soil contaminated by wood preservatives. A leaching batch experiment was conducted using two soils, a highly contaminated soil (1033 mg kg(-1) As and 371 mg kg(-1) Cr) and slightly contaminated soil (22 5mg kg(-1) As and 27 mg kg(-1) Cr). Compared to an untreated reference soil, amendment with 5% WTR reduced leaching in the highly contaminated soil by 91% for Cr and 98% for As. No aging effect was observed after 103 d. In a small field experiment, soil was mixed with 2.5% WTR in situ. Pore water was extracted during 3 years from the amended soil and a control site. Pore water arsenic concentrations in the amended soil were more than two orders of magnitude lower than in the control for the upper samplers. An increased release of arsenic was observed during winter in both fields, mostly in the deepest samplers. This is likely due to the formation of a pseudo-gley because of precipitation surplus. Stabilization of arsenic and chromium contaminated soil using WTR is a promising method but the transformation of ferrihydrite in soil proves a concern in case of waterlogged soils. Still the amendment minimized the leaching of arsenic, even in cases of seasonal releases.


[Splenic necrosis after percutaneous celiac plexus block guided by ultrasonography].
Celiac plexus block guided by ultrasonography is an efficient technique for treatment of pain due to solar syndrome. Neurological complication of this therapeutic method can be avoided using an anterior route. We report the occurrence of splenic necrosis after celiac plexus block, which represents an exceptional complication of the therapeutic procedure.


Telomere length and outcome in heart failure.
Telomeres are causally involved in senescence. Senescence is a potential factor in the pathogenesis and progression of heart failure. In heart failure telomeres are shorter, but the prognostic value associated with telomere length has not been defined. Telomere length was prospectively determined by quantitative polymerase chain reaction in 890 patients with New York Heart Association (NYHA) functional class II to IV heart failure. After 18 months, we examined the association between telomere length and the predefined primary end-point: time to death or hospitalization for heart failure. Mean age of the patients was 71 years, 39% were women, 51% were in NYHA class II, and 49% were in class III/IV. A total of 344 patients reached the primary end-point (130 deaths and 214 hospitalizations). Patients with shorter telomeres were at an increased risk of reaching the primary end-point (hazard ratio 1.79; 95% confidence interval (CI) 1.21-2.63). In multivariate analysis shorter telomere length remained associated with a higher risk for death or hospitalization (hazard ratio, 1.74; 95% CI 1.07-2.95) after adjustment for age of heart failure onset, gender, hemoglobin, renal function, and N-terminal pro-B-type natriuretic peptide level, a history of stroke, atrial fibrillation, and diabetes. Shorter length of telomeres predicts the occurrence of death or hospitalization in patients with chronic heart failure.


Hemichorea-Hemiballism as a Delayed Manifestation of Hyperglycemia: A Case Report.
Hemichorea is characterized by involuntary, continuous, non-patterned movements on one side of the body. While it is most commonly caused by strokes, it can also be caused by metabolic derangements such as hyperglycemia. We present two patients who developed hemichorea in the setting of hyperglycemia. Our first patient had a history of uncontrolled diabetes mellitus and developed chorea 2 weeks following a hyperglycemic event. The second patient developed chorea while being on steroids for hip pain and was later diagnosed to have underlying diabetes mellitus. MRI showed hyperintensity in the contralateral lentiform nucleus in both cases. The chorea did not improve despite the correction of the hyperglycemia. Both patients were started on Tetrabenazine with significant improvement. Hyperglycemia-induced hemichorea might be underdiagnosed given the prevalence of diabetes mellitus in the population. Chorea can even be the presenting symptom of diabetes mellitus and in some cases is a delayed manifestation of hyperglycemia.


Analysis of HIV Integrase Resistance in Black Men Who Have Sex with Men in the United States.
Resistance to reverse transcriptase and protease inhibitors was frequently detected in HIV from black men who have sex with men (MSM) enrolled in the HIV prevention trials network (HPTN) 061 study. In this study, integrase strand transfer inhibitor (INSTI) resistance was analyzed in black MSM enrolled in HPTN 061 (134 infected at enrollment and 23 seroconverters) and a follow-up study, HPTN 073 (eight seroconverters). The ViroSeq HIV-1 Integrase Genotyping Kit (Abbott Molecular) was used for analysis. Major INSTI resistance mutations were not detected in any of the samples. HIV from 14 (8.4%) of the 165 men, including 4 (12.9%) of 31 seroconverters, had accessory or polymorphic INSTI-associated mutations. The most frequently detected mutation was E157Q. These findings are promising because INSTI-based regimens are now recommended for first-line antiretroviral treatment and because long-acting cabotegravir is being evaluated for pre-exposure prophylaxis.


Comparing the diagnosis of white matter injury in premature newborns with serial MR imaging and transfontanel ultrasonography findings.
The accurate identification of white matter injury in premature neonates is important for counseling parents and for targeting these high risk neonates for appropriate rehabilitation services. The objective of this study was to compare the diagnosis of white matter injury detected by serial MR imaging and ultrasonography of a contemporary cohort of premature neonates. Each of the 32 consecutively enrolled neonates was studied with MR imaging at a median postconceptional age of 31.9 weeks (range, 27.6-38.1 weeks) and again at a median postconceptional age of 36.5 weeks (range, 33.4-42.9 weeks) and with serial ultrasonography according to a clinical protocol. Because periventricular echogenicity shown on ultrasonograms evolves over time, both the highest grade of echogenicity and the grade of echogenicity shown on the last neonatal ultrasonogram were used in the analysis to determine the predictive values and correlation (Spearman's rho) of ultrasonography for predicting white matter abnormalities shown on MR images. White matter abnormalities were diagnosed in 18 (56%) neonates based on MR imaging, consisting of foci of scattered T1 hyperintensity in the periventricular white matter, and in 22 (69%) neonates based on ultrasonography, consisting of abnormal periventricular echogenicity. The severity of white matter abnormalities shown by MR imaging was not correlated with the highest grade of white matter abnormalities detected with ultrasonography (rho=0.18, P=.3) or with the grade of white matter abnormalities shown on the last ultrasonogram (rho = 0.16, P=.4). Although ultrasonography is commonly used to screen premature neonates for white matter injury, it was not a sensitive predictor of the milder spectrum of MR imaging-defined white matter abnormalities.


TBX2 is preferentially amplified in BRCA1- and BRCA2-related breast tumors.
The chromosome 17q23 region is frequently amplified in breast tumors. Gain of the region is present in 50% of BRCA1-associated breast tumors and 87% of BRCA2-associated breast tumors. The amplification frequency of the RPS6KB1 and TBX2 oncogenes from this amplicon was compared in 27 BRCA1 and BRCA2 mutant breast tumors, 15 breast tumors from high-risk patients with no BRCA1 or BRCA2 mutations, and 62 matched sporadic breast tumor controls. TBX2 was determined to be preferentially amplified and overexpressed in BRCA1 and BRCA2 mutant tumors, whereas RPS6KB1 was not, suggesting a role for TBX2 amplification in the development of BRCA1- and BRCA2-associated breast tumors.


Unmet need for family planning and barriers to contraceptive use in Kaduna, Nigeria: culture, myths and perceptions.
In 2017, just one-fifth of all married women of reproductive age reported using contraception in Kaduna state, Nigeria, while many more experienced unmet need for contraception. These realities drive risky fertility behaviours and compromise reproductive rights. This study explored the determinants of low modern contraceptive uptake and persistent unmet need among women in the state. Nine focus group discussions were conducted with married women who met study criteria for unmet need, and who had different levels of access to contraception. Discussions confirmed that many women in Kaduna do not feel empowered to make contraceptive decisions. Yet there is a growing preference for smaller families and decreased stigmatisation of contracepting women. Barriers at home, in the community and in health facilities impose a ceiling on the extent to which women's fertility desires may be achieved. These include cultural, normative, social and financial factors, such as the need for husband's permission to access services, service providers' insistence on spousal consent, subtle and overt pressures to use folkloric approaches by religious leaders, and high real, or perceived, out-of-pocket costs. These findings suggest that Kaduna is on the cusp of social change and study findings can be translated into programmatic interventions to improve voluntary uptake of contraception.


Hypocholesterolemic effects of Lactobacillus reuteri LR6 in rats fed on high-cholesterol diet.
The bacterium Lactobacillus reuteri LR6, an isolate from breast-fed human infant feces, was tested positive for bile tolerance and bile salt hydrolase activity. It was also evaluated as a potential probiotic with cholesterol-lowering effect in vivo. In this study, 32 male Albino rats were divided into four groups consisting of eight mice per group. For 60 d, group I was fed with normal synthetic diet, group II was fed with cholesterol-enriched diet only, group III was fed with cholesterol-enriched diet supplemented with skimmed milk, and group IV was fed with cholesterol-enriched diet supplemented with L. reuteri LR6-fermented skimmed milk (10(8) cfu/mL). Blood samples were taken to study lipid profile on 0th, 15th, 30th and 60th day. Compared with the control group, the values for total cholesterol (TC), triglyceride (TG), and LDL were reduced significantly in group fed with L. reuteri LR6 but for HDL this difference was not significant. The results indicated that L. reuteri LR6 might be effective as a probiotic with cholesterol-lowering activities.


Self-assembly and hybridization mechanisms of DNA with cationic polythiophene.
The combination of DNA and π-conjugated polyelectrolytes (CPEs) represents a promising approach to develop DNA hybridization biosensors, with potential applications for instance in the detection of DNA lesions and single-nucleotide polymorphisms. Here we exploit the remarkable optical properties of a cationic poly[3-(6'-(trimethylphosphonium)hexyl)thiophene-2,5-diyl] (CPT) to decipher the self-assembly of DNA and CPT. The ssDNA/CPT complexes have chiroptical signatures in the CPT absorption region that are strongly dependent on the DNA sequence, which we relate to differences in supramolecular interactions between the thiophene monomers and the various nucleobases. By studying DNA-DNA hybridization and melting processes on preformed ssDNA/CPT complexes, we observe sequence-dependent mechanisms that can yield DNA-condensed aggregates. Heating-cooling cycles show that non-equilibrium mixtures can form, noticeably depending on the working sequence of the hybridization experiment. These results are of high importance for the use of π-conjugated polyelectrolytes in DNA hybridization biosensors and in polyplexes.


Orai3 TM3 point mutation G158C alters kinetics of 2-APB-induced gating by disulfide bridge formation with TM2 C101.
After endoplasmic reticulum (ER) Ca(2+) store depletion, Orai channels in the plasma membrane (PM) are activated directly by ER-resident STIM proteins to form the Ca(2+)-selective Ca(2+) release-activated Ca(2+) (CRAC) channel. However, in the absence of Ca(2+) store depletion and STIM interaction, the mammalian homologue Orai3 can be activated by 2-aminoethyl diphenylborinate (2-APB), resulting in a nonselective cation conductance characterized by biphasic inward and outward rectification. Here, we use site-directed mutagenesis and patch-clamp analysis to better understand the mechanism by which 2-APB activates Orai3. We find that point mutation of glycine 158 in the third transmembrane (TM) segment to cysteine, but not alanine, slows the kinetics of 2-APB activation and prevents complete channel closure upon 2-APB washout. The "slow" phenotype exhibited by Orai3 mutant G158C reveals distinct open states, characterized by variable reversal potentials. The slow phenotype can be reversed by application of the reducing reagent bis(2-mercaptoethylsulfone) (BMS), but in a state-dependent manner, only during 2-APB activation. Moreover, the double mutant C101G/G158C, in which an endogenous TM2 cysteine is changed to glycine, does not exhibit altered kinetics of 2-APB activation. We suggest that a disulfide bridge, formed between the introduced cysteine at TM3 position 158 and the endogenous cysteine at TM2 position 101, hinders transitions between Orai3 open and closed states. Our data provide functional confirmation of the proximity of these two residues and suggest a location within the Orai3 protein that is sensitive to the actions of 2-APB.


An Fc-receptor activity of plasma membranes from guinea-pig peritoneal polymorphonuclear leucocytes.
Plasma membranes prepared from guinea-pig peritoneal polymorphonuclear leucocytes showed an immune-complex-binding activity that corresponded well with the activity in intact cells. The characteristics of this activity were reversible binding, dependence on the Fc portion of antigen-complexed IgG (immunoglobulin G), competition with aggregated IgG and independence from energy metabolism. These results support the conclusion that the binding activity found in the isolated plasma membranes is an Fc-receptor activity of guinea-pig peritoneal polymorphonuclear leucocytes. The activity showed Kd = 6.7 x 10(-8) M-IgG and maximum binding of 17 pmol of IgG/mg of membrane protein when measured with an immune complex of alpha-amylase and homologous guinea-pig anti-(alpha-amylase) IgG. Inhibition of the Fc-receptor activity by a series of various salts indicated the contribution of the hydrophobic interaction to the binding. Inhibitory effects of salts or metal-chelating reagents on the Fc-receptor activity were also observed on superoxide generation by these cells induced by the immune complex, suggesting a role of the Fc receptor as the immune-complex-binding site responsible for the initiation of superoxide generation.


Targeting EGFR and ALK in NSCLC: current evidence and future perspective.
The advent of molecular therapy targeting specific driver oncogenes has dramatically changed the prognosis of a subset of NSCLC, dilating survival and improving the quality of life of patients with advanced disease. Two of the major targets for treatment with receptor TKIs are the activated mutated forms of the EGFR and the ALK gene fusions. In advanced NSCLC patients harboring EGFR mutations or ALK rearrangements, the use of TKIs in the first-line setting, have provided unexpected large progression-free survival and overall survival benefits, compared with cytotoxic chemotherapy. However, despite initial responses and durable remissions, the development of resistance inevitably leads to treatment failure. The aim of this review is to discuss the treatment strategy currently used for tumors harboring these two genetic targets and to focus on what will be available in clinical practice in the near future.


Circulating levels of vasoactive peptides in patients with acute bacterial meningitis.
The underlying mechanisms for cerebral blood flow (CBF) abnormalities in acute bacterial meningitis (ABM) are largely unknown. Putative mediators include vasoactive peptides, e.g. calcitonin-gene related peptide (CGRP), vasoactive intestinal peptide (VIP), and endothelin-1 (ET-1), all of which may be affected by therapeutic interventions used in the intensive care unit. We measured arterial levels as well as the net cerebral flux of these peptides in patients with ABM, and in healthy volunteers undergoing interventions relevant to intensive care. Seven patients with severe ABM and sepsis and fifteen healthy volunteers were included after informed consent. The net cerebral fluxes of vasoactive peptides were measured by the Kety-Schmidt technique in ABM patients (baseline study only), as well as in volunteers at baseline, during voluntary hyperventilation, after an intravenous injection of lipopolysaccharide (LPS), and during norepinephrine infusion. The arterial levels of CGRP, but not of VIP or ET-1, were elevated in patients with ABM, but no net cerebral flux was present. CGRP levels decreased during hyperventilation and after LPS injection. No net cerebral flux of VIP occurred in any group at any time. A cerebral efflux of ET-1, which occurred in volunteers at baseline, was neither present in volunteers after LPS injection nor in patients with ABM. The arterial concentration of the vasodilatory peptide, CGRP, but of neither VIP nor the vasoconstrictor ET-1, is elevated in patients with ABM and sepsis. A constitutive cerebral output of ET-1 appears to be present in healthy humans, but is abolished after LPS injection.


Petroleum's Park: How Oil Shaped the Palisades Interstate Park, 1900-1960.
This article argues that oil played an important role in shaping park landscapes in the United States. Scholars have shown how early road building sought to integrate the view of the natural landscape from the driver's seat. The acceptance of roads as a major feature of parks, like in the Palisades, shows the primacy of oil as a foundation of American life in the twentieth century. This article goes a step further and analyzes in depth how oil, oil wealth, and road technologies changed how people experienced nature. The Palisades Interstate Park, located in New Jersey and New York in the United States, became known by the parkway it contained. Philanthropists, notably John D. Rockefeller Jr., park authorities, and public planning officials all believed the park should contain a parkway made specifically for leisurely drivers who could take in the scenery from the comfort of their car. In the first half of the twentieth century, they reshaped the Palisades into a motorist's paradise. At the Palisades, the consumption of gasoline was written both on the landscape and into the cultural practice of exploring the natural beauty of the cliffs.


Early surgeon impressions and technical difficulty associated with laparoendoscopic single-site surgery: a Society of American Gastrointestinal and Endoscopic Surgeons Learning Center study.
Interest in laparoendoscopic single-site surgery (LESS) is growing rapidly among surgeons. This study aimed to characterize current surgeon impressions about LESS and to determine the relative difficulty of performing a simulated LESS task using a multiport access device. This study was conducted at the 2009 Society of Gastrointestinal Endoscopic Surgeons (SAGES) Learning Center. The 56 study participants were asked to complete pre- and post-test questionnaires regarding their level of training, prior clinical experience, and opinions about LESS. Technical skill performance was evaluated using the standardized fundamentals of laparoscopic surgery Peg Transfer task scored according to time and error metrics. The participants completed three repetitions: conventional laparoscopy (LAP), LESS with nonarticulated instruments (LESS Straight), and LESS with articulated instruments (LESS Articulating). Complete data were collected for 45 (80%) of the 56 participants, which included 27 practicing surgeons, nine minimally invasive surgery (MIS) fellows, seven residents, and two allied health professionals. Five surgeons (LESS experienced) had managed at least one LESS case in the preceding 6 months. Participants rated their comfort with LESS as 2.0 ± 1.2 (5-point scale, 1 = very uncomfortable). Compared with conventional laparoscopy, the participants indicated that LESS had 97% better cosmesis, 25% decreased postoperative pain, 18% faster recovery, 97% more demanding, 73% increased rate of complications, and 82% anticipated wide adoption. They all indicated a readiness to offer LESS to their patients if appropriately trained. Peg Transfer performance was significantly worse for LESS than for LAP (40-65% performance decline), and for LESS Articulating than for LESS Straight (44% performance decline). Construct validity for the LESS simulated tasks was supported because the LESS-experienced scores were significantly better than the LESS-nonexpert scores. Despite the increased technical difficulty associated with the LESS approach, surgeons are enthusiastic about offering these techniques and seeking additional training. Robust simulation-based methods that foster skill acquisition through repetitive practice and verification of proficiency are needed such that safe adoption may be fostered.


Neurophysiological characterization of postherniotomy pain.
Inguinal herniotomy is one of the most frequent surgical procedures and chronic pain affecting everyday activities is reported in approximately 10% of patients. However, the neurophysiological changes and underlying pathophysiological mechanisms of postherniotomy pain are not known in detail, thereby precluding advances in treatment strategies and prophylaxis. Therefore, we examined forty-six patients reporting moderate to severe postherniotomy pain affecting daily activities for more than a year postoperatively, and compared them with a control group of patients without pain 1 yr postoperatively. A quantitative sensory testing protocol was used, assessing sensory dysfunction type, location and severity. We assessed the protocol test-retest variability using data from healthy control subjects. All patients (pain and pain-free) had signs of nerve damage, seen as sensory dysfunction. Detection thresholds for tactile and warmth stimulation were significantly increased while cold detection and pressure pain detection thresholds were significantly decreased in pain patients compared to controls. Repetitive punctuate and brush stimulation resulted in significantly more frequent and intense pain on the painful side than on the unaffected side in pain patients, and was not observed in controls. Our findings showed large and small fiber dysfunction in both pain and pain-free patients but more profound in pain patients and with signs of central sensitization (abnormal temporal summation). The specific finding of reduced pain detection threshold over the external inguinal annulus is consistent with damage to the cutaneous innervation territory of nervous structures in the inguinal region. The correspondence between pain location and sensory disturbance suggests that the pain is neuropathic in nature. Whether the underlying pathophysiological mechanisms are related to direct intraoperative nerve injury or nerve injury due to an inflammatory mesh response remains to be determined.


Self-Awareness: Nucleic Acid-Driven Inflammation and the Type I Interferonopathies.
Recognition of foreign nucleic acids is the primary mechanism by which a type I interferon-mediated antiviral response is triggered. Given that human cells are replete with DNA and RNA, this evolutionary strategy poses an inherent biological challenge, i.e., the fundamental requirement to reliably differentiate self-nucleic acids from nonself nucleic acids. We suggest that the group of Mendelian inborn errors of immunity referred to as the type I interferonopathies relate to a breakdown of self/nonself discrimination, with the associated mutant genotypes involving molecules playing direct or indirect roles in nucleic acid signaling. This perspective begs the question as to the sources of self-derived nucleic acids that drive an inappropriate immune response. Resolving this question will provide fundamental insights into immune tolerance, antiviral signaling, and complex autoinflammatory disease states. Here we develop these ideas, discussing type I interferonopathies within the broader framework of nucleic acid-driven inflammation.


Human tissue oversight in hospitals: an AABB survey.
Reports of human tissue allograft-transmitted infections have underscored the need for better accounting of allografts in health-care facilities. The Joint Commission on Accreditation of Healthcare Organizations (JCAHO) implemented new storage and issuance tissue standards for hospital oversight as of July 1, 2005. This study sought to survey hospital tissue responsibilities. The AABB Tissue Task Force conducted a Web-based survey distributed to all 904 hospital institutional members in January 2005. The survey asked about tissue type used, breadth of responsibility, hospital department involvement, and views on AABB involvement. Data from 402 of 904 (45%) respondents were tabulated and analyzed. Among the 402 respondents, 325 (81%) used allogeneic and/or autologous human tissue. The most frequently used tissues were musculoskeletal (n = 240, 74%) and skin (n = 169, 52%) allografts. The department of surgery (e.g., operating room; n = 245, 76%) most often had responsibility for tissue use, followed by the blood bank (i.e., transfusion service; n = 164, 51%); surgery most frequently had responsibility for all tissue types except peripheral blood progenitor cells. Only 32 of 402 (8%) respondents had plans for increased oversight in the next 12 months; 129 of 178 (72%) thought there was a role for AABB in developing guidance on hospital tissue responsibilities. In this survey, most AABB member hospital respondents indicated facility use of allogeneic and/or autologous tissues. Although tissue allograft responsibility by surgery was extensive, hospital blood banks also had significant involvement. Few blood banks, however, plan increased oversight in the near future. Given JCAHO standards, blood banks have an opportunity to assist their hospital in planning for assigned tissue responsibilities and oversight to ensure patient safety.


A Multidimensional, Multi-tiered System of Supports Model to Promote School Attendance and Address School Absenteeism.
School attendance and school completion are important benchmarks of successful development. Unfortunately, school absenteeism and school dropout remain debilitating and prevalent conditions among youth. Stakeholders invested in promoting school attendance and reducing school absenteeism generally agree that multifaceted ecological frameworks are needed to account for these heterogeneous problems as well as differences across local education agencies and broader jurisdictions. A multi-tiered system of supports (MTSS) framework emphasizes many aspects that match well with school attendance and its problems, including prevention and a continuum of supports, screening, evidence-based assessment and intervention, problem-solving and data-based decision-making, implementation fidelity, and natural embedding into extant school improvement plans. This article outlines a multidimensional MTSS model for school attendance and absenteeism to account for recent developments regarding service delivery within schools. Such developments include integrated models of multi-tiered service delivery to concurrently address multiple domains of functioning, the development of more nuanced approaches for students with various challenges, and consideration of three-dimensional (pyramidal) perspectives to allow simultaneous and yet nuanced strategies for several domain clusters. Sample domain clusters common to the literature that could populate the multiple dimensions or sides of a MTSS pyramid model for school attendance and absenteeism are presented. These domain clusters include (1) school refusal/truancy/school withdrawal/school exclusion, (2) functional profiles and analysis, (3) preschool/elementary/middle/high school, (4) ecological levels of impact on school attendance and its problems, and (5) low/moderate/high absenteeism severity. Recommendations are made as well regarding broader MTSS integration and implementation science vis-à-vis school attendance and its problems.


Serum albumin binds beta- and alpha-monoolein in vitro.
We investigated the interaction of bovine serum albumin (BSA) and monoolein (MO) and estimated the number of BSA binding sites for the alpha- and beta-isomers of MO. The turbidity of increasing concentrations of aqueous dispersions of alpha-MO and beta-MO in the presence and absence of BSA was measured in triplicate by absorption spectrophotometry. Aqueous dispersions of [13C(1)]MO and [13C(1)]MO/BSA mixtures at molar ratios of 1:1, 3:1 and 5:1 were analyzed in duplicate by [13C]nuclear magnetic resonance (NMR) at pH 7.4 and 36 degrees C. BSA bound significantly more beta-MO than alpha-MO at 15 min: 5.4 +/- 0.42 and 3.3 +/- 0.60 mol MO/mol BSA, respectively (P: < 0.05). [13C]NMR spectra of the 1:1 molar ratio of [13C(1)]MO /BSA exhibited a single carbonyl peak at 175.19 ppm, whereas spectra of 3:1 and 5:1 molar ratios exhibited three peaks between 172 and 174 (ppm), each distinct from carbonyl resonances of either [13C(1)]MO dispersed in water, 176.72 (ppm) or BSA alone. The intensities of individual peaks, but not their chemical shift values, varied between 3:1 and 5:1 molar ratios, indicating that BSA has at least three MO binding sites and may bind up to five molecules of MO per molecule. This study confirms that serum albumin binds MO in vitro and supports the theory that albumin transports monoglycerides produced by lipoprotein lipase hydrolysis of triglyceride.


Death of the King: The Introduction of Vaccination into Nepal in 1816.
This article explores the introduction of smallpox vaccination into Nepal in 1816 at the request of the Nepalese government; the king, however, was not vaccinated, contracted the disease and died. British hopes that vaccination would be extended throughout the country did not eventuate. The article examines the significance of this early appearance of vaccination in Nepal for both Nepalese and British, and relates it to the longer history of smallpox control and eventual eradication. When the Nepalese requested World Health Organization (WHO) assistance with communicable disease control in the mid-twentieth century little had changed for most Nepalese. We know about the events in 1816 through the letters of the newly imposed British Resident after Nepal's military defeat in the Anglo-Nepal War (1814-16). By also drawing on other sources and foregrounding Nepal, it becomes possible to build up a more extensive picture of smallpox in Nepal that shows not only boundaries and limits to colonial authority and influence but also how governments may adopt and use technologies on their own terms and for their own purposes. Linking 1816 to the ultimately successful global eradication programme 150 years later reminds us of the need to think longer term as to why policies and programmes may or may not work as planned.


Stable isotope resolved metabolomics classification of prostate cancer cells using hyperpolarized NMR data.
Metabolic fingerprinting is a strong tool for characterization of biological phenotypes. Classification with machine learning is a critical component in the discrimination of molecular determinants. Cellular activity can be traced using stable isotope labelling of metabolites from which information on cellular pathways may be obtained. Nuclear magnetic resonance (NMR) spectroscopy is, due to its ability to trace labelling in specific atom positions, a method of choice for such metabolic activity measurements. In this study, we used hyperpolarization in the form of dissolution Dynamic Nuclear Polarization (dDNP) NMR to measure signal enhanced isotope labelled metabolites reporting on pathway activity from four different prostate cancer cell lines. The spectra have a high signal-to-noise, with less than 30 signals reporting on 10 metabolic reactions. This allows easy extraction and straightforward interpretation of spectral data. Four metabolite signals selected using a Random Forest algorithm allowed a classification with Support Vector Machines between aggressive and indolent cancer cells with 96.9% accuracy, -corresponding to 31 out of 32 samples. This demonstrates that the information contained in the few features measured with dDNP NMR, is sufficient and robust for performing binary classification based on the metabolic activity of cultured prostate cancer cells.


Accuracy analysis in laser keratopography.
We analyze the accuracy of a laser keratopographer in the evaluation of corneal topography for non-smooth corneal surfaces and when some noise is introduced into measured data. Through some numerical simulations, cosinesoidal deformations with different amplitudes and spatial periods are introduced on theoretical surfaces. Gaussian noise is introduced on the simulated x and y position coordinates for the measured position of the reflected beam in order to simulate detection errors that are due to vibrations or electric and other noise on the position-sensing detector. We found that the topography of the surface could be obtained with reliable accuracy if the height-to-width ratio of the deformations of the surface is smaller than 0.02 and the error in the detection of position at the position-sensing detector is under 0.5 mm.


Long-distance colonization, isolation by distance, and historical demography in a relictual Mexican pinyon pine (Pinus nelsonii Shaw) as revealed by paternally inherited genetic markers (cpSSRs).
Pinus nelsonii is a relictual pinyon pine distributed across a wide altitudinal range in semiarid zones in Mexico near the border between the States of Nuevo León and Tamaulipas. It also occurs in small patches in the State of San Luis Potosí. Pinus nelsonii is classified in the monotypic subsection Nelsoniae, separated from other pinyon pines (subsection Cembroides), because it possesses several distinctive characters including persistent fascicle sheaths, connate needles, and a distinctive wood anatomy. In the present study, chloroplast simple sequence repeats (cpSSRs) were used to estimate genetic variation in most known populations (nine) of P. nelsonii. The genetic variation (HT = 0.73; 27 haplotypes in 256 individuals) is moderate when compared to other pine species. Population differentiation ranged between low and moderate (FST = 0.13 and RST = 0.05), as did the Nei and Goldstein genetic distances between populations. However, this pattern varied depending on whether the infinite alleles or stepwise mutation model was used. In the former case a significant isolation by distance was found, but not in the latter. A significant association between geographical and genetic structure in one clade, through a nested clade analysis, was found, which suggested long-distance colonization between 125000 and 309000 years ago. We found weak evidence for a population expansion. A mismatch distribution suggests that P. nelsonii populations underwent an expansion 4.25 times their size between 59000 and 146000 years ago. On the other hand, the populations' star-like phylogeny and a slight parabolic relationship between coalescence times and lineage number also suggest weak population expansion. Overall, this species appears to have been in demographic stasis for a large proportion of the time detected by the markers used.


Metabolic Glycoengineering-Programmed Nondestructive Capture of Circulating Tumor Cells.
Circulating tumor cells (CTCs) are the "seeds" for malignant tumor metastasis, and they serve as an ideal target for minimally invasive tumor diagnosis. Abnormal glycolysis in tumor cells, characterized by glycometabolism disorder, has been reported as a universal phenomenon observed in various types of tumors. This provides a potential powerful tool for universal CTC capture. However, to the best of our knowledge, no metabolic glycoengineering-based CTC capture strategies have been reported. Here, we proposed a nondestructive CTC capture method based on metabolic glycoengineering and a nanotechnology-based proximity effect, allowing for highly specific, sensitive, and universal CTC capture. To achieve this goal, cells are first labeled with DNA tags through metabolic glycoengineering and then captured through a DNA tetrahedra-functionalized dual-tentacle magnetic nanodevice. Due to the difference in metabolic performance, only tumor cells are labeled with more densely packed DNA tags and captured through enhanced intermolecular interaction mediated by the proximity effect. In summary, we have constructed a versatile platform for nondestructive CTC capture, offering a novel perspective for the application of CTC liquid biopsy in tumor diagnosis and treatment.


Estrogens are essential for male pubertal periosteal bone expansion.
The skeletal response to estrogen therapy was studied in a 17-yr-old boy with congenital aromatase deficiency. As expected, estrogen therapy (1 mg estradiol valeriate/d from age 17 until 20 yr) normalized total and free testosterone and reduced the rate of bone remodeling. Dual-energy x-ray absorptiometry-assessed areal bone mineral density (BMD) of the lumbar spine and femoral neck increased significantly (by 23% and 14%, respectively), but peripheral quantitative computed tomography at the ultradistal radius revealed no gain of either trabecular or cortical volumetric BMD. The increase in areal BMD was thus driven by an increase in bone size. Indeed, longitudinal bone growth (height, +8.5%) and especially cross-sectional area of the radius (+46%) and cortical thickness (+12%), as measured by peripheral quantitative computed tomography, increased markedly during estrogen treatment. These findings demonstrate that androgens alone are insufficient, whereas estrogens are essential for the process of pubertal periosteal bone expansion typically associated with the male bone phenotype.


Turkish women's knowledge and views regarding mother's milk banking.
The main aim of the study was to determine the knowledge and views of Eastern Anatolian women towards mother's milk banking. The descriptive research was conducted between March and May 2009. The study population comprised 350 married women aged between 15 and 49 years who gave birth and who were registered with a family health center in Erzurum, Turkey. The data were collected by a questionnaire form. The questionnaire form included open-ended and closed questions regarding the descriptive characteristics and about knowledge and views of mothers on milk banking. The questionnaire form was completed by the women individually. Of the women surveyed, 90.6% indicated they had not previously heard anything about breast milk banking, 64.0% said that they could donate their milk, 36.3% stated it constituted a problem from a religious aspect, and 28.9% said it leads to social and moral problems. The hospital and maternity authorities may consider establishing a "milk mother file". This report addresses the first step in raising awareness of the valuable contribution of donor milk to babies and the organization of human milk donation for use in a neonatal intensive care unit.


Tyrosine phosphorylation-dependent suppression of a voltage-gated K+ channel in T lymphocytes upon Fas stimulation.
Selective cell death plays a critical role in the development of the immune system and in the elimination of target cells expressing foreign antigens. Most of programmed cell death occurs by apoptosis. Apoptotic cell death of lymphocytes can be triggered by ligation of APO-1/Fas (CD95) antigen (Suda, T., and Nagata, S. (1994) J. Exp. Med. 179, 873-879; Nagata, S., and Golstein, P. (1995) Science 267, 1449-1456). We find that activation of Fas leads to the inhibition of the voltage-dependent n-type K+ channels (Kv1.3) studied by patch clamp technique in Jurkat T lymphocytes. Tyrosine kinases have been shown to be crucial in Fas-induced cell death (Eischen, C. M., Dick, C. J., and Leibson, P. J. (1994) J. Immunol. 153, 1947-1954). The inhibition of the current is correlated with the tyrosine phosphorylation of immunoprecipitated and blotted K+ channel protein. We show, that the Src-like protein-tyrosine kinase inhibitor herbimycin A and the deficiency of the p56(lck) tyrosine kinase in mutant Jurkat cells abolished the channel inhibition and phosphorylation by anti-Fas antibody, while reconstitution of the p56(lck) kinase partly restored these effects of Fas receptor triggering. These results suggest a regulation of n-type K+ channels by tyrosine kinases upon Fas receptor triggering, which might be important for apoptosis.


Highlighting Interleukin-36 Signalling in Plaque Psoriasis and Pustular Psoriasis.
Plaque psoriasis and pustular psoriasis are overlapping, but distinct, disorders. The therapeutic response to biologics supports the pivotal role of the tumour necrosis alpha (TNF-?)/ interleukin (IL)-23/IL-17/IL-22 axis in the pathogenesis of these disorders. Recently, functional activation of the IL-36 receptor (IL-36R) was discovered to be another driving force in the pathogenesis of psoriasis. This was first highlighted by the discovery that a loss-of-function mutation of the IL-36R antagonist (IL-36Ra) causes pustular psoriasis. Although the TNF-?/IL-23/IL-17/IL-22 axis and the functional activation of IL-36R are fundamentally involved in plaque psoriasis and pustular psoriasis, respectively, the 2 pathways are closely related and mutually reinforced, resulting in full-blown clinical manifestations. This review summarizes current topics on how IL-36 agonists (IL-36?, IL-36?, IL-36?) signal IL-36R, the pathological expression of IL-36 agonists and IL-36Ra in plaque and pustular psoriatic lesions, and the cross-talk between the TNF-?/IL-23/IL-17/IL-22 axis and the functional activation of IL-36R in the epidermal milieu.


The GREENH-City interventional research protocol on health in all policies.
This paper presents the research protocol of the GoveRnance for Equity, EnviroNment and Health in the City (GREENH-City) project funded by the National Institute for Cancer (Subvention N°2017-003-INCA). In France, health inequities have tended to increase since the late 1980s. Numerous studies show the influence of social, economic, geographic and political determinants on health inequities across the life course. Exposure to environmental factors is uneven across the population and may impact on health and health inequities. In cities, green spaces contribute to creating healthy settings which may help tackle health inequities. Health in All Policies (HiAP) represents one of the key strategies for addressing social and environmental determinants of health inequities. The objective of this research is to identify the most promising interventions to operationalize the HiAP approaches at the city level to tackle health inequities through urban green spaces. It is a participatory interventional research to analyze public policy in real life setting (WHO Healthy Cities). It is a mixed method systemic study with a quantitative approach for the 80 cities and a comparative qualitative multiple case-studies of 6 cities. The research combines 3 different lens: 1/a political analysis of how municipalities apply HiAP to reduce social inequities of health through green space policies and interventions 2/a geographical and topological characterization of green spaces and 3/ on-site observations of the use of green spaces by the inhabitants. City profiles will be identified regarding their HiAP approaches and the extent to which these cities address social inequities in health as part of their green space policy action. The analysis of the transferability of the results will inform policy recommendations in the rest of the Health City Network and widely for the French municipalities. The study will help identify factors enabling the implementation of the HiAP approach at a municipal level, promoting the development of green spaces policies in urban areas in order to tackle the social inequities in health.


No melatonin suppression by illumination of popliteal fossae or eyelids.
A recent report that popliteal illumination shifted the circadian rhythms of body temperature and melatonin challenged the longstanding belief that light phase-shifting the circadian system in mammals is mediated only through the retina. The authors tested effects of popliteal illumination and illumination provided through the eyelids on melatonin suppression. In randomized, counterbalanced orders, healthy volunteers received three treatments from midnight until 2:00 AM, one on each of three visits to the laboratory. Treatments included (1) no illumination from light pads applied to the popliteal fossae, with light mask maintained at < 3 lux (control); (2) light mask illuminated at 1700 lux, with popliteal light pads extinguished; and (3) popliteal light pads illuminated (13,000 lux) and light mask at < 3 lux (control). Saliva specimens were sampled at midnight, at 1:00 AM, and at 2:00 AM. Mean salivary melatonin concentrations rose from an average of 30.8 (3.9) pg/ml at midnight (baseline), to 33.2 (4.0) pg/ml at 1:00 AM, and to 37.2 (3.8) pg/ml at 2:00 AM in all three conditions, but no statistical differences were found using repeated-measures ANOVA. No evidence of melatonin suppression by either popliteal or closed eyelid light stimulation was found. These data suggest that bright retinal illumination is necessary for suppression of melatonin mediated through the suprachiasmatic nuclei.


Generation of tunable narrowband pulses initiating from a femtosecond optical parametric amplifier.
We report a tunable optical pulse expander capable of producing narrowband long pulses, starting from a femtosecond optical parametric amplifier (OPA), which is based on chirp-matched frequency mixing technique. The device delivers nJ-level pulses with bandwidth of ~0.1 nm and duration of ~45 ps within its tuning range from 1000 nm to 1090 nm. The combination of a femtosecond OPA and a pulse expander may provide synchronized and both tunable femtosecond and tens of picoseconds pulses simultaneously, which should be promising in the applications where both temporal and spectral resolutions are needed.


EXPLORING MEDICAL STUDENTS' COMPETENCY IN UNDERSTANDING PRIMARY IMMUNODEFICIENCY DISEASES IN INDIA.
Primary Immunodeficiency Disease (PID) represents a class of diverse illnesses marked by compromised immune system performance. For better patient outcomes, PIDs must be diagnosed and treated quickly. Medical graduates are essential to the detection and treatment of these illnesses. The purpose of this study was to evaluate medical students' knowledge about PIDs in different Indian medical colleges. To perform this analytical investigation, college students from Maharashtra-area universities were enlisted between March and April of 2023. The participants received a questionnaire from mediators from every institution. Of the 500 students in the study, 66% were between the ages of 22 and 24 and 52% were female. Their understanding ratings had an average of 16.3±6.2 and varied between 4 and 32. A set of students classified as below average (86%) and a mean/above average (14%), were separated among the students. The largest percentage of above-average knowledge was demonstrated by VI-year participants (p<0.05). This investigation emphasizes how critical it is to provide focused educational activities to improve medical students' comprehension of PIDs in India.


Adolescent use of the combined oral contraceptive pill: a retrospective observational study.
To determine the extent of combined oral contraceptive use by girls aged 10-16 years in Scotland. Assessment of combined oral contraceptive prescribing in 35 414 girls for the year 1 November 1999-31 October 2000 from data retrieved from 161 primary care practices taking part in the Scottish Programme for Improving Clinical Effectiveness in Primary Care, and from national aggregated data from family planning clinics. During the study period the oral contraceptive pill (OCP) was prescribed by a primary care physician to 1531 girls (4.3%) aged 10-16 years. The age specific prevalence rates per 1000 girls registered with their family doctor rose from 0.9/1000 girls aged 12 years or younger, to 6.9, 30, 86.3, and 174.8/1000 for girls aged 13, 14, 15, and 16 years respectively. The overall prevalence of combined oral contraceptive prescribing by primary care physicians was 43.2/1000 girls aged 10-16 years. A further 1765 girls aged 13-16 years obtained a prescription for the OCP from a Scottish family planning clinic, giving an overall prevalence rate for family planning clinic prescribing of 8.0/1000 girls aged 10-16 years. Despite reportedly high levels of sexual activity and teenage pregnancy in this age group, these results confirm that OCP use is relatively low. The UK has the highest rate of teenage pregnancy in Western Europe, but despite the medical and social concerns about the sexual health of teenagers, the level of oral contraceptive use in this young age group remains low.


Measuring the economic and social consequences of CVDs and diabetes in India and Pakistan.
In India and Pakistan, CVD and diabetes has assumed alarming levels. However,governments in these countries are ill-prepared for coping with this epidemic. This paper reviews the literature for those studies which have addressed the current and foreseen economic and social consequences of CVDs and diabetes in India and Pakistan. This review adopts a societal perspective by incorporating the impact on the individual, the household, and the health and economic sectors. The review finds that in both countries there has been a paucity of systematic efforts to measure the economic and social impact of CVDs and diabetes. Moreover, the review has found an absence of assessments of direct and indirect costs in the same study, inattention to the social consequences of these diseases and methodological inconsistencies which make comparative analyses restrictive. It is critically important that a research base of studies investigating the impact of the diseases in India and Pakistan be undertaken. Gathering these data is critical since both countries have many competing health priorities reflected in the intransigency of key health indicators and the data emerging from these countries suggests that the social gradient is reversing. Therefore, in the absence of hard evidence to these diseases are likely to remain outside of mainstream public health planning. With these data in hand, the choice for health planners with regard to important decisions may become clearer. Similarly, the implications for productivity and revenue earnings make a powerful argument in order to focus the attention of private sector employers on these issues.


The effects of amplitude normalization and EMG targets on cVEMP interaural amplitude asymmetry.
The purpose of this investigation was to determine whether the use of visual feedback of tonic electromyographic (EMG) activity, or the use of amplitude normalization techniques would reduce significantly the variability in cervical vestibular evoked myogenic potential (cVEMP) P13-N23 interaural amplitude asymmetry data in otologically and neurologically intact children and adults. There were 97 subjects, both pediatric and adult, from whom the authors recorded cVEMPs with and without the use of an EMG target and amplitude normalization techniques. The four conditions were: (1) conventional recording (condition 1), (2) conventional recording with an EMG target (condition 2), (3) same as condition 1, with the addition of postacquisition amplitude normalization techniques, and (4) same as condition 2, with the addition of postacquisition amplitude normalization techniques. The absolute peak to peak amplitude of positive-negative response (P13-N23), absolute latency of P13, and the left or right amplitude asymmetry of P13-N23 were measured. Neither P13-N23 amplitudes nor latencies, neither mean root mean square (RMS) of the full wave rectified EMG activity, nor the standard deviation of the RMS EMG activity differed significantly when subjects were, and were not, asked to ensure their tonic EMG activity exceeded a visual target (i.e., representing >50 µV RMS EMG). Amplitude normalization of the cVEMP waveforms failed to reduce significantly the variability in the amplitude asymmetry data. Activating the sternocleidomastoid muscle with the patient in a semirecumbent position, with head turned away from the stimulated ear and head elevated (i.e., an optimal activation technique) was sufficient to produce the highest amplitude cVEMPs with an acceptable amount of variability in subjects of all ages. Group data suggested that the use of visual targets and amplitude normalization routines did not reduce significantly the variability in cVEMP interaural amplitude asymmetry measures. However, in isolated cases amplitude normalization converted an "abnormal" cVEMP into a "normal" cVEMP although the reverse occurred as well, suggesting that these techniques may be beneficial for a subset of patients receiving a less than perfectly administered test procedure.


An evaluation of terminal-restriction fragment length polymorphism (T-RFLP) analysis for the study of microbial community structure and dynamics.
A systematic evaluation of the value and potential of terminal-restriction fragment length polymorphism (T-RFLP) analysis for the study of microbial community structure has been undertaken. The reproducibility and robustness of the method has been assessed using environmental DNA samples isolated directly from PCB-polluted or pristine soil, and subsequent polymerase chain reaction (PCR) amplification of total community 16S rDNA. An initial investigation to assess the variability both within and between different polyacrylamide gel electrophoresis (PAGE) runs showed that almost identical community profiles were consistently produced from the same sample. Similarly, very little variability was observed as a result of variation between replicate restriction digestions, PCR amplifications or between replicate DNA isolations. Decreasing concentrations of template DNA produced a decline in both the complexity and the intensity of fragments present in the community profile, with no additional fragments detected in the higher dilutions that were not already present when more original template DNA was used. Reducing the number of cycles of PCR produced similar results. The greatest variation between profiles generated from the same DNA sample was produced using different Taq DNA polymerases, while lower levels of variability were found between PCR products that had been produced using different annealing temperatures. Incomplete digestion by the restriction enzyme may, as a result of the generation of partially digested fragments, lead to an overestimation of the overall diversity within a community. The results obtained indicate that, once standardized, T-RFLP analysis is a highly reproducible and robust technique that yields high-quality fingerprints consisting of fragments of precise sizes, which, in principle, could be phylogenetically assigned, once an appropriate database is constructed.


High Density of Periaortic Adipose Tissue in Abdominal Aortic Aneurysm.
Perivascular adipose tissue (PVAT) is currently seen as a paracrine organ that produces vasoactive substances, including inflammatory agents, which may have an impact on the vasculature. In this study PVAT density was quantified in patients with an aortic aneurysm and compared with those with a non-dilated aorta. Since chronic inflammation, as the pathway to medial thinning, is a hallmark of abdominal aortic aneurysms (AAAs), it was hypothesised that PVAT density is higher in AAA patients. In this multicentre retrospective case control study, three groups of patients were included: non-treated asymptomatic AAA (n = 140), aortoiliac occlusive disease (AIOD) (n = 104), and individuals without aortic pathology (n = 97). A Hounsfield units based analysis was performed by computed tomography (CT). As a proxy for PVAT, the density of adipose tissue 10 mm circumferential to the infrarenal aorta was analysed in each consecutive CT slice. Intra-individual PVAT differences were reported as the difference in PVAT density between the region of the maximum AAA diameter (or the mid-aortic region in patients with AIOD or controls) and the two uppermost slices of infrarenal non-dilated aorta just below the renal arteries. Furthermore, subcutaneous (SAT) and visceral (VAT) adipose tissue measurements were performed. Linear models were fitted to assess the association between the study groups, different adipose tissue compartments, and between adipose tissue compartments and aortic dimensions. AAA patients presented higher intra-individual PVAT differences, with higher PVAT density around the aneurysm sac than the healthy neck. This association persisted after adjustment for cardiovascular risk factors and diseases and other fat compartments (β = 13.175, SE 4.732, p = .006). Furthermore, intra-individual PVAT differences presented the highest correlation with aortic volume that persisted after adjustment for other fat compartments, body mass index, sex, and age (β = 0.566, 0.200, p = .005). The results suggest a relation between the deposition of PVAT and AAA pathophysiology. Further research should explore the exact underlying processes.


Virus-lymphocyte interactions during the course of immunosuppressive virus infection.
Malignant rabbit fibroma virus (MV) is a lymphocytotropic leporipoxvirus which produces profound immunological dysfunction and lethal fibromyxosarcoma. We examined virus recovery from splenic lymphocytes as a function of time after inoculation in vivo, and correlated this with both immunological function and expression of virus-induced host suppressor activity. MV was most abundant in lymphocytes obtained 4 days following inoculation. At that time, immune function was relatively normal and host suppressor activity was not observed. By 7 days after infection, when active host immunosuppressor functions were observed, virus recovery was decreased. Eleven days post-inoculation host immune function began to recover despite increasing virus-induced tumours and developing opportunistic infection. Simultaneously, MV was no longer recoverable from spleen cells. Spleen cells from day 11 tumour-bearing rabbits did not support MV replication as efficiently as did normal or day 4 or 7 splenic lymphocytes, but they did not alter the ability of MV to grow in the latter cells. By fluorescence examination and cytofluorography, splenic lymphocytes bearing MV antigens were abundant 7 days after infection but disappeared by 11 days. This was temporally related to production of neutralizing antibody to MV, and development of virus-specific lymphocyte proliferative activity. The composition of splenic lymphocytes changed as well: the normal ratio of about 1:1 for B and T cells changed to 1:2 by day 7, and then inverted to almost 2:1 by day 11. Rabbits infected with MV thus appear to recover their immune function, concurrently eliminate virus-infected lymphocytes, and elaborate high titres of neutralizing serum antibodies despite progressive infections and tumour development.


Pulmonary emphysema associated with the FZ alpha 1-antitrypsin phenotype.
In one family three brothers were found to have a moderate deficiency of alpha 1-antitrypsin associated with the unusual Pi (protease inhibitor) phenotype FZ. The Pi phenotypes of their six living siblings were found to be FM (in three), M (in two) and MZ (in one). The three FZ brothers all had moderate to severe obstructive airways disease, and two had at least moderately severe pulmonary emphysema. Additional risk factors included moderate cigarette smoking in two and prolonged exposure to grain dust in all three. The same risk factors applied to the six non-FZ siblings, but they had only mild symptoms and pulmonary dysfunction or no lung problems at all; one, a female smoker with the MZ phenotype, had probable early emphysema demonstrated radiologically. The three FZ men may have had reduced fertility, as they produced only 1 child among them, as compared with 39 among the other eight siblings. This family study thus suggests that individuals with the FZ phenotype are at risk for pulmonary emphysema and chronic obstructive airways disease, particularly in the presence of other risk factors, such as cigarette smoking and grain dust exposure.


Partial-Body Cryotherapy Exposure 2 Hours Prior to a Shuttle Run Does Not Enhance Running Performance.
To determine whether a single acute preexercise bout of partial-body cryotherapy (PBC) enhanced maximal-effort shuttle run performance, salivary enzyme concentration, and self-reported performance readiness. A total of 18 male rugby league players (age = 20.1 [0.5] y; mass = 91.4 [12.4] kg) were exposed to either PBC for 3 minutes at -136°C (1°C) or a control condition prior to a continuous, high-intensity 6 × 40-m shuttle run test. Passive saliva samples were collected to determine salivary alpha amylase (sAA) concentration. Perceived performance readiness and well-being questionnaires were completed using a 1-to-7 Likert scale. The PBC exposure did not elicit a greater improvement in 6 × 40-m shuttle run performance in comparison with the control condition (standardized difference; +0.4 [5.9%]; P = .881; mean ± 90% confidence limits). The increase in sAA concentration was moderately greater 15 minutes after PBC compared with the control group (+67 [32%], P = .012) and remained moderately higher up to 2 hours post-PBC exposure compared with the control condition (+41 [40%], P = .045). There were greater improvements in self-reported perceptions of muscle soreness (+0.6 [0.4%], P = .043; units ±90% confidence limits) and mood (+0.6 [0.7%], P = .038) after PBC compared with control. It appears that a single 3-minute bout of PBC does not augment maximal effort shuttle run performance in elite rugby league players. Beneficial increases in sAA concentration, coupled with improved perceptions of muscle soreness and mood, should be explored further for alternative training or precompetition practices.


Diagnostic techniques for evaluating herpes simplex virus infections. Laboratory considerations.
Recent advances in the management and treatment of genital herpes simplex virus (HSV) infections underscore the importance of timely and accurate diagnosis of the disease. Moreover, increased physician awareness of the importance of accurately diagnosing herpes has led to a better understanding of its natural history. Like all diagnostic medical devices, microbiologic tests used to diagnose HSV infections are subject to governmental regulations. Based on the current status of available testing and our knowledge of the nature of HSV, clearly there is still much to be learned about HSV infections. The answers to some key questions will provide advances in diagnostic expertise and, ultimately, in the effective treatment and prevention of HSV-associated illness.


Point of Care- A Novel Approach to Periodontal Diagnosis-A Review.
Periodontal disease, one of the prevalent oral diseases, is characterized by gingival inflammation and periodontal tissue destruction. Diagnosing this disease is challenging to the clinicians as the disease process is discontinuous and shows periods of exacerbation and remission. Traditional diagnostic methods basically tells about the past tissue destruction so new diagnostic methods are required which is able to detect the active state of the disease, determine the future progression and also estimates the response to the therapy, thereby helping in the better clinical management of the patient. Both saliva and Gingival crevicular fluid (GCF) are believed to be reliable medium to detect the biomarkers which plays a pivotal role in measuring the disease activity. Keeping these observations in mind rapid chairside tests are developed to diagnose periodontal disease called as Point of Care (POC) diagnostics which simplifies diagnosis and helps in improving the prognosis. This review article highlights about the biomarkers used in the diagnosis and throws light on the various available point of care diagnostic devices.


Intake of Common Alcoholic and Non-Alcoholic Beverages and Breast Cancer Risk among Japanese Women: Findings from the Japan Collaborative Cohort Study.
This study investigated the association between intake of common alcoholic and non-alcoholic beverages and breast cancer risk among Japanese women. This study included 33,396 Japanese women aged 40-79 years from 24 areas in Japan from the Collaborative Cohort study. During the follow-up period (≥20 years), 245 incidents or mortal breast cancers were documented. Multivariable logistic regression analysis was performed to assess the independent association between breast cancer risk and the intake of Japanese green tea, coffee, and alcohol. Japanese green tea was the most commonly consumed non-alcoholic beverage (81.6% of participants), followed by coffee (34.7%) and alcohol (23.6%). No significant associations were identified between the intake of green tea and coffee with breast cancer risk (odds ratio OR 1.15, 95% confidence interval [CI] 0.82-1.60, and OR 0.84, 95% CI 0.64-1.10, respectively). Alcohol intake was associated with significant breast cancer risk (OR 1.46, 95% CI 1.11-1.92), and even infrequent alcohol consumption (.