The emerging role of alemtuzumab in chronic lymphocytic leukemia.
Targeted therapy for malignant hematologic disorders has become a realistic goal with the identification of novel antibodies that are designed to act against highly expressed antigens on malignant clones. CD52 is abundantly expressed on malignant lymphocytes in chronic lymphocytic leukemia (CLL). Alemtuzumab is a humanized monoclonal antibody that targets CD52 and induces cell death by several mechanisms that are still under investigation. The initial positive results of many clinical studies that explored the activity of alemtuzumab in relapsed and/or refractory CLL have provoked many oncologists to incorporate this agent into the treatment paradigm of this disease. Prophylactic antibiotics for the duration of therapy or until patients are no longer immunocompromised are recommended. This review summarizes the clinical experience with alemtuzumab that eventually led to its approval. Recent novel prognostic factors and trends in CLL therapy are also reviewed.


Evaluation of genetic variability in micropropagated propagules of ornamental pineapple [Ananas comosus var. bracteatus (Lindley) Coppens and Leal] using RAPD markers.
The objective of the present study was to evaluate the genetic variability in micropropagated plantlets of ornamental pineapple, after the fourth period of subculture. The basal culture medium consisted of MS salts, vitamins, 3% sucrose, liquid formulation, supplemented with 6-benzylaminopurine (BAP) at concentrations of 0.125, 0.25, 0.5, 1.0, and 2.0 mg/L. The addition of BAP influenced the occurrence of genetic variation revealed using random amplified polymorphic DNA (RAPD) markers. Of a total of 520 primers tested, 44 were selected and amplified; 402 monomorphic bands (97.2%) and 18 polymorphic bands (2.8%) resulted among regenerated plantlets. The polymorphic fragments were produced by 12 primers (OPA-01, OPA-20, OPB-01, OPB-19, OPC-19, OPF-13, OPL-17, OPM-13, OPP-16, OPT-07, OPV-19, and OPX-03). Among the primers that identified polymorphism, OPA-01, OPA-20, OPB-19, OPC-19, OPL-17, OPP-16, and OPX-3 each showed, one polymorphic band and OPF-13 amplified a maximum of three bands. In this study, the RAPD technique was effective in showing the occurrence of somaclonal variations that occur during the micropropagation process of ornamental pineapple cultivation in BAP-supplemented medium, and it is possible to detect the presence of genetic variation in early stages of plant development.


Montelukast in paediatric asthma and allergic rhinitis: a systematic review and meta-analysis.
We aim to assess the impact of montelukast on paediatric patients with asthma/allergic rhinitis, measured using patient-reported outcome measures, compared with other treatments or placebo. Protocol registration CRD42020216098 (www.crd.york.ac.uk/PROSPERO). MEDLINE and Embase databases were used to conduct the search. Two authors independently selected studies and extracted data, and a third reviewer resolved discrepancies. Meta-analyses were constructed to estimate the standardised mean difference (SMD) using a random-effects model. Out of 3937 articles identified, 49 studies met the inclusion criteria, mostly randomised clinical trials (sample sizes: 21-689 patients). The SMD of change pooled estimators for the global, mental and physical domains of health-related quality of life were not statistically significant. For daytime and night-time symptoms scores, the SMD (95% CI) was in favour of inhaled corticosteroids (-0.12, -0.20- -0.05 and -0.23, -0.41- -0.06, respectively). The pooled estimator for global asthma symptoms was better for montelukast when compared with placebo (0.90, 0.44-1.36). The synthesis of the available evidence suggests that, in children and adolescents, montelukast was effective in controlling asthma symptoms when compared with placebo, but inhaled corticosteroids were superior in controlling symptoms, especially at night-time. These findings of our systematic review concur with current guidelines for asthma treatment.


Pattern of pain, duct morphology, and pancreatic function in chronic pancreatitis. A comparative study.
In 101 patients with suspected or definite chronic pancreatitis a pancreatic function test, endoscopic retrograde pancreatography, and an interview with special regard to pain were performed. Decrease in pancreatic function was correlated to dilatation of the pancreatic duct system. However, no correlation between the duct morphology and the severity of pain was found. Patients with pancreatic pseudocysts were evenly distributed among the groups in accordance with pancreatic function, but they seemed to be concentrated in the groups with severe pain.


The effect of transfers between health care facilities on costs and length of stay for pediatric burn patients.
Hospitals vary widely in the services they offer to care for pediatric burn patients. When a hospital does not have the ability or capacity to handle a pediatric burn, the decision often is made to transfer the patient to another short-term hospital. Transfers may be based on available specialty coverage for children; which adult and non-teaching hospitals may not have available. The effect these transfers have on costs and length of stay (LOS) has on pediatric burn patients is not well established and is warranted given the prominent view that pediatric hospitals are inefficient or more costly. The authors examined inpatient admissions for pediatric burn patients in 2003, 2006, and 2009 using the Kids' Inpatient Database, which is part of the Healthcare Cost and Utilization Project. ICD-9-CM codes 940 to 947 were used to define burn injury. The authors tested if transfer status was associated with LOS and total charges for pediatric burn patients, while adjusting for traditional risk factors (eg, age, TBSA, insurance status, type of hospital [pediatric vs adult; teaching vs nonteaching]) by using generalized linear mixed-effects modeling. A total of n = 28,777 children had a burn injury. Transfer status (P < .001) and TBSA (P < .001) was independently associated with LOS, while age, insurance status, and type of hospital were not associated with LOS. Similarly, transfer status (P < .001) and TBSA (P < .001) was independently associated with total charges, while age, insurance status, and type of hospital were not associated with total charges. In addition, the data suggest that the more severe pediatric burn patients are being transferred from adult and non-teaching hospitals to pediatric and teaching hospitals, which may explain the increased costs and LOS seen at pediatric hospitals. Larger more severe burns are being transferred to pediatric hospitals with the ability or capacity to handle these conditions in the pediatric population, which has a dramatic impact on costs and LOS. As a result, unadjusted, pediatric hospitals are seen as being inefficient in treating pediatric burns. However, since pediatric hospitals see more severe cases, after adjustment, type of hospital did not influence costs and LOS. TBSA and transfer status were the predictors studied that independently affect costs and LOS.


Subtle Variations in Dietary-Fiber Fine Structure Differentially Influence the Composition and Metabolic Function of Gut Microbiota.
The chemical structures of soluble fiber carbohydrates vary from source to source due to numerous possible linkage configurations among monomers. However, it has not been elucidated whether subtle structural variations might impact soluble fiber fermentation by colonic microbiota. In this study, we tested the hypothesis that subtle structural variations in a soluble polysaccharide govern the community structure and metabolic output of fermenting microbiota. We performed in vitro fecal fermentation studies using arabinoxylans (AXs) from different classes of wheat (hard red spring [AXHRS], hard red winter [AXHRW], and spring red winter [AXSRW]) with identical initial microbiota. Carbohydrate analyses revealed that AXSRW was characterized by a significantly shorter backbone and increased branching compared with those of the hard varieties. Amplicon sequencing demonstrated that fermentation of AXSRW resulted in a distinct community structure of significantly higher richness and evenness than those of hard-AX-fermenting cultures. AXSRW favored OTUs within Bacteroides, whereas AXHRW and AXHRS favored Prevotella Accordingly, metabolic output varied between hard and soft varieties; higher propionate production was observed with AXSRW and higher butyrate and acetate with AXHRW and AXHRS This study showed that subtle changes in the structure of a dietary fiber may strongly influence the composition and function of colonic microbiota, further suggesting that physiological functions of dietary fibers are highly structure dependent. Thus, studies focusing on interactions among dietary fiber, gut microbiota, and health outcomes should better characterize the structures of the carbohydrates employed.IMPORTANCE Diet, especially with respect to consumption of dietary fibers, is well recognized as one of the most important factors shaping the colonic microbiota composition. Accordingly, many studies have been conducted to explore dietary fiber types that could predictably manipulate the colonic microbiota for improved health. However, the majority of these studies underappreciate the vastness of fiber structures in terms of their microbial utilization and omit detailed carbohydrate structural analysis. In some cases, this causes conflicting results to arise between studies using (theoretically) the same fibers. In this investigation, by performing in vitro fecal fermentation studies using bran arabinoxylans obtained from different classes of wheat, we showed that even subtle changes in the structure of a dietary fiber result in divergent microbial communities and metabolic outputs. This underscores the need for much higher structural resolution in studies investigating interactions of dietary fibers with gut microbiota, both in vitro and in vivo.


Genital self-mutilation.
A 53-year-old man was brought to the emergency department having removed both testicles and amputated his penis using a bread knife. Examination of the amputated penis showed it to be unsuitable for an attempted replant procedure. The patient was taken to theatre where the perineal wound was debrided and the remaining urethra brought down as a perineal urethrostomy, with a local cutaneous flap rotated to provide coverage for the urethra. Discussed herein are the incidence, predisposing factors, management and complications of genital self-mutilation in the adult male, and the existing literature is reviewed on the subject.


Identification of a kinetically distinct activity of 11beta-hydroxysteroid dehydrogenase in rat Leydig cells.
Leydig cells are susceptible to direct glucocorticoid-mediated inhibition of testosterone biosynthesis but can counteract the inhibition through 11beta-hydroxysteroid dehydrogenase (11beta-HSD), which oxidatively inactivates glucocorticoids. Of the two isoforms of 11beta-HSD that have been identified, type I is an NADP(H)-dependent oxidoreductase that is relatively insensitive to inhibition by end product and carbenoxolone (CBX). The type I form has been shown to be predominantly reductive in liver parenchymal cells and other tissues. In contrast, type II, which is postulated to confer specificity in mineralocorticoid receptor (MR)-mediated responses, acts as an NAD-dependent oxidase that is potently inhibited by both end product and CBX. The identity of the 11beta-HSD isoform in Leydig cells is uncertain, because the protein in this cell is recognized by an anti-type I 11beta-HSD antibody, but the activity is primarily oxidative, more closely resembling type II. The goal of the present study was to determine whether the kinetic properties of 11beta-HSD in Leydig cells are consistent with type I, type II, or neither. Leydig cells were purified from male Sprague-Dawley rats (250 g), and 11beta-HSD was evaluated in Leydig cells by measuring rates of oxidation and reduction, cofactor preference, and inhibition by end product and CBX. Leydig cells were assayed for type I and II 11beta-HSD and MR messenger RNAs (mRNAs), and for type I 11beta-HSD protein. Leydig cell 11beta-HSD had bidirectional catalytic activity that was NADP(H)-dependent. This is consistent with the hypothesis that type I 11beta-HSD is present in rat Leydig cells. However, unlike the type I 11beta-HSD in liver parenchymal cells, the Leydig cell 11beta-HSD was predominantly oxidative. Moreover, analysis of kinetics revealed two components, the first being low a Michaelis-Menten constant (Km) NADP-dependent oxidative activity with a Km of 41.5 +/- 9.3 nM and maximum velocity (Vmax) of 7.1 +/- 1.2 pmol x min x 10(6) cells. The second component consisted of high Km activities that were consistent with type I:NADP-dependent oxidative activity with Km of 5.87 +/- 0.46 microM and Vmax of 419 +/- 17 pmol x min x 10(6) cells, and NADPH-dependent reductive activity with Km of 0.892 +/- 0.051 microM and Vmax of 117 +/- 6 pmol x min x 10(6) cells. The results for end product and CBX inhibition were also inconsistent with a single kinetic activity in Leydig cells. Type I 11beta-HSD mRNA and protein were both present in Leydig cells, whereas type II mRNA was undetectable. We conclude that the low Km NADP-dependent oxidative activity of 11beta-HSD in Leydig cells does not confirm to the established characteristics of type I and may reside in a new form of this protein. We also demonstrated the presence of the mRNA for MR in Leydig cells, and the low Km component could allow for specificity in MR-mediated responses.


[Mismatch negativity in the brain evoked potentials induced by short duration acoustic stimuli in adolescents in the norm and those with attention deficit].
The effect of stimulus duration on the mismatch negativity of the auditory event-related potentials was studied in healthy children and those with attention-deficit symptoms. The minimum stimulus duration with which a MMN was elicited by frequency deviant was 50 ms in healthy children. The MMN was absent with shorter stimuli (11 ms and 30 ms). These parametres are close to those in adults. As to children with attention-deficit symptoms the MMN was insignificant with all tested stimulus durations (11 ms, 30 ms, 50 ms).


Family therapy with single, young adults.
Family therapy with the single, young adult can be successfully carried out using the Bowen family systems theory when the process is staged over time. The therapist who has gone back into his or her own family of origin can be of greatest help as a "coach" to the client in this ongoing process. The therapist assists the client in a process of orderly differentiation that enables the client to develop a more solid sense of self. Reactive distance and emotional cut-offs are modified as solutions to anxiety. More personal, flexible family, peer, and work relationships are promoted. The client's initial presenting problems diminish as he/she comes to terms with his/her ultimate aloneness and self-responsibility, and begins to accept family members as they are and relationships with them for what they can be.


Continuity of care after discharge from ICU.
Patients and their relatives may feel unsupported in general wards and the community after the high level of care received in ICUs. Some general nurses may not have enough experience to deal with the high-dependency needs of patients discharged from ICUs to ward care. It is recommended that a follow-up nurse assess the needs of ICU patients and ensure provision has been made for their return to the community.


AL Amyloidosis Presenting With Crescentic Glomerulonephritis.
Kidney amyloidosis typically presents with nephrotic-range proteinuria. Rare cases of crescentic glomerulonephritis have been reported in patients with kidney amyloidosis but most cases were in the setting of patients with AA amyloidosis from long-standing inflammation and malignancy. We present a case of a previously healthy man in his 70s who was admitted with severe acute kidney injury, nephrotic-range proteinuria, and nephritic urinary sediment. Initial serologic testing for causes of rapidly progressive glomerulonephritis were negative. Kidney biopsy demonstrated the presence of active cellular and fibrocellular crescents with Congo red-positive staining in glomeruli and microvasculature on light microscopy and amyloid fibrils in glomerular basement membrane on electron microscopy. Urinary protein electrophoresis revealed monoclonal λ light chains, leading to a diagnosis of kidney AL amyloidosis, which was confirmed with bone marrow biopsy. Our case illustrates that AL amyloidosis can present with findings suspicious for rapidly progressive glomerulonephritis and crescent formation on kidney biopsy specimens.


Residual ridge dimensions at edentulous maxillary first molar sites and periodontal bone loss among two ethnic cohorts seeking tooth replacement.
To study residual ridge dimensions at edentulous first molar sites in relation to periodontal bone loss among cohorts of partially edentulous Asian Indian and Hong Kong Chinese subjects seeking tooth replacement. A total of 628 edentulous maxillary first molar sites were analyzed on Cone Beam Computed Tomography scans of 225 Asian Indian (I) and 232 Hong Kong Chinese (C) partially edentulous adults seeking tooth replacement. Age, ethnicity, gender, total tooth loss, the presence or absence of adjacent teeth, categories of periodontal status defined according to radiographic alveolar bone loss (P0: periodontal health, P1: incipient to moderate disease, P2: severe periodontal disease) and sinus membrane abnormalities were noted. Alveolar ridge height (RH), widths at 1 and 3 mm from crest (RW1; RW3), and relative position of the bone crest (RR) were measured. Prevalence of P2 status was most frequent in both cohorts(C: 50.4% I: 49.2%). P2 had lowest ridge heights; 13.1% C P2 and 14%I P2 had RH < 2 mm. Sites with both RH <8 mm and RW1 < 6 mm occurred at 59%C P2 and 68%I P2. Sinus membrane abnormalities were most frequent in P2. Periodontal status and sinus membrane abnormality increased the odds of RH <5 mm and RH <8 mm more than 2-fold; additionally, gender and ethnicity significantly impacted RH <8 mm. Gender and adjacent tooth status significantly affected RW1. Incident advanced periodontal disease was common among Asian Indian and Hong Kong Chinese subjects seeking tooth replacement and associated with lower available bone heights. Ethnicity, gender, sinus membrane thickening affected available bone height in the subsinus region, while the presence of adjacent teeth- and age-affected residual ridge width.


Prognostic factors of minimally invasive follicular thyroid carcinoma: extensive vascular invasion significantly affects patient prognosis.
Follicular thyroid carcinoma (FTC) is divided into two categories: minimally and widely invasive FTC. Generally, the prognosis of minimally invasive FTC is excellent, but patients showing certain characteristics have a dire prognosis. In this study, we investigated the prognostic factors of minimally invasive FTC using a series of 292 patients. On multivariate analysis, extensive (4 or more) vascular invasion, age ≥ 45 years, and tumor size > 4 cm were independent prognostic factors of patient disease-free survival (DFS). Distant metastasis at diagnosis (M1) was the strongest prognostic factor of cause-specific survival (CSS). Extensive vascular invasion and tumor size > 4 cm also independently affected patient carcinoma death. Capsular invasion was not related to patient prognosis. The ten-year DFS rate of patients with extensive vascular invasion was 80%, which was poorer than that of those having tumor size > 4 cm (91%) and aged 45 years or older (90%). These findings suggest that 1) M1 most strongly affects the CSS of patients, and 2) M0 patients with extensive vascular invasion may be candidates for completion total thyroidectomy and radioactive iodine ablation.


Gypenosides induced apoptosis in human colon cancer cells through the mitochondria-dependent pathways and activation of caspase-3.
The effects of the gypenosides (Gyp), a component of Gynostemma pentaphyllum Makino, on the cell viability, cell cycle and induction of apoptosis were investigated in human colon cancer colo 205 cells. Gyp was cytotoxic to colo 205 cells with an IC50 of 113.5 microg/ml. The decreasing number of viable cells appeared to be due to the induction of cell cycle arrest and apoptotic cell death, since Gyp induced morphological changes and internucleosomal DNA fragmentation and increased the sub-G1 group. The production of reactive oxygen species and Ca2+ and the depolarization of mitochondrial membrane potential were observed, dose- and time-dependently, after treatment with various concentrations of Gyp. Gyp treatment also gradually decreased the expression of the anti-apoptotic proteins Bcl-2 and Bcl-xl, but increased the expression of the pro-apoptotic protein Bax. Gyp increased the levels of p53 and promoted the release of cytochrome c and the activation of caspase-3 before leading to apoptosis. These results provide information towards an understanding of the mechanisms by which Gyp induces cell cycle arrest and apoptosis in human colon cancer cells.


Usefulness of non-invasive cardiac output monitoring in elderly patients undergoing monopolar transurethral resection of the prostate: a pilot study.
To assess the impact of irrigating fluid on hemodynamic profiles using real-time non-invasive cardiac output monitoring (NICOM) in elderly patients undergoing monopolar transurethral resection of the prostate (TURP). Twenty patients between 65 and 80 years of age who were scheduled for monopolar TURP and received spinal anesthesia up to T10 were enrolled. Irrigating fluid (2.7% sorbitol with 0.5% mannitol solution) was used. Hemodynamic profiles including cardiac index, and stroke volume variation (SVV) using NICOM were obtained. Estimated irrigating fluid absorption was indirectly calculated. The median amount of irrigating fluid used was 6000 mL. The median SVV was 11%, which increased to 12% at 10 minutes after initiating surgery. No significant changes in the cardiac index were observed. The estimated absorption of irrigating fluid was almost zero. Although the estimated amount of irrigating fluid that was absorbed was negligible, the increase in SVV may indicate intravascular volume depletion with diuresis resulting from mannitol in the irrigating fluid early during irrigation. Therefore, even during short irrigating times, intensive hemodynamic monitoring should be performed to monitor the possibility of intravascular volume depletion as well as volume overload, especially immediately after large amounts of irrigating fluid are used.


Detection of the GSTM1*0 allele by long polymerase chain reaction.
Approximately 50% of individuals in most human populations completely lack activity of the detoxifying enzyme glutathione S-transferase M1. The medical consequences of this deficiency have been extensively investigated in molecular epidemiological studies, but possible differences of the highly active homozygous genotype versus the moderately active heterozygous genotype could not be considered because many currently used polymerase chain reaction (PCR) assays cannot distinguish the homozygous genotypes GSTM1 *A/A and GSTM1*B/B from the heterozygous genotypes GSTM1*A/0 and GSTM1*B/0. Here, we describe that long PCR is suitable for this purpose by specifically producing a signal for the GSTM1*0 allele. Based on the published cluster of GSTM genes (GSTM1 to -M5), a 13-kb segment spanning the site of the GSTM1 deletion was amplified using a GSTM2-specific forward primer (5'-CATCGCTTATGATGTCCTTGAGAGAAACCAAG-3') and a reverse primer, which is specific for the upstream region of GSTMS (5'-GCGTTTCTGAGGACTGGACTGATGATCG-3'). Any failure in the amplification was controlled by co-amplification of a 15-kb human tissue plasminogen activator gene fragment. The GSTM1*0-specific 13-kb amplicon appears in all carriers of one or two null alleles, but in none of the 14 tested GST1*A/B samples which served as controls since individuals with this genotype are known to lack any GSTM1*0 allele. While conventional PCR assays for detection of the GSTM1 deletion differentiated homozygously deficient from hetero- or homozygously active individuals, this long PCR assay differentiates homozygously active from hetero- or homozygously deficient individuals. Using both assays, an unambiguous differentiation into carriers of zero, one or two active alleles of GSTM1 is possible.


Differential proteome expression analysis of androgen-dependent and -independent pathways in LNCaP prostate cancer cells.
Prostate cancer (PC) is one of the leading causes of cancer death in men. It commonly develops in older males, but the number of younger men diagnosed with the disease has increased in recent years. Hormone therapies, such as chemical and surgical methods that inhibit androgen synthesis or androgen receptor (AR) activation, have been used for advanced disease. However, castration-resistant PC (CRPC), which exhibits androgen-independent mechanisms for activating AR, develops after a few years of such treatment and no therapy is available. In this study, we examined differences in the proteomes associated with the androgen-dependent (DHT treatment) and -independent (FSK, forskolin treatment) AR signaling conditions in LNCaP prostate cancer cells. Moreover, we used EPI-001, which inhibits AR-mediated transcriptional activity, to examine whether the observed differences in protein expression were directly affected by AR-mediated mechanisms. A total of 213 protein spots were matched in our 2-dimensional gel electrophoresis (2DE) analysis and 8 proteins with significant expression changes in our 5 different treatment groups were identified by mass spectrometry. Among these proteins, expression levels of PEPCK-M, catalase, tubulin alpha chain, alpha-enolase, and endoplasmic reticulum resident protein 29 were significantly altered by DHT and the levels of HSP 90 and EF-Tu were changed by FSK. These changes were blocked by EPI-001 in DHT-regulated proteins, PEPCK-M, catalase, and tubulin alpha chain and FSK-regulated EF-Tu protein. The results from our immunohistochemical analysis using in vivo xenograft models were consistent with the 2DE data. We therefore report the first identification of differences in proteins that are significantly regulated under androgen-dependent and -independent AR signaling conditions. Our findings could suggest a possible molecular mechanism through which AR is activated in the absence and/or presence of androgen, and might help explain the inhibitory action of EPI-001 on CRPC.


Expression and gene polymorphisms of interleukin 28B and hepatitis B virus infection in a Chinese Han population.
Recent genome-wide association studies found that genetic polymorphisms near the IL28B gene is strongly associated with sustained viral response and spontaneous viral clearance in chronically infected hepatitis C patients. We aimed to evaluate the effects of IL28B variations on hepatitis B virus (HBV) infection in a Chinese Han population and to explore the association between IL28B polymorphisms and susceptibility to infection, viral clearance, disease progression, viral load and liver inflammation. We determined three IL28B single gene polymorphisms (rs12979860, rs12980275 and rs8099917) in 203 individuals with chronic HBV infection, 203 individuals with self-limited HBV infection and 203 individuals negative for all HBV seromarkers. Interleukin (IL)28B serum levels were evaluated in all subjects. Additionally, peripheral blood mononuclear cells from 42 chronically HBV-infected individuals were subjected to whole-genome expression studies. The association among genotype, allele and haplotype frequencies of IL28B with alanine aminotransferase levels and HBV DNA was established. However, no significant differences were observed in genotype or allele frequencies among chronically HBV-infected, self-limited and healthy subjects. The serum IL28B level was lower in patients with chronic HBV infection than in the self-limited HBV-infected or healthy subjects. The serum IL28B level was correlated with the subject's genotype. Gene expression micro-array analysis showed enhanced IL28B expression in patients with low HBV viral load. Variability at the IL28B locus is associated with HBV viral load and hepatic inflammation. Genetic variation of IL28B may prevent HBV progression by reducing viral load and liver inflammation, providing a valuable gene therapy tool.


Modulation of TRP Channel Activity by Hydroxylation and Its Therapeutic Potential.
Two transient receptor potential (TRP) channels-TRPA1 and TRPV3-are post-translationally hydroxylated, resulting in oxygen-dependent regulation of channel activity. The enzymes responsible are the HIF prolyl hydroxylases (PHDs) and the asparaginyl hydroxylase factor inhibiting HIF (FIH). The PHDs and FIH are well characterized for their hydroxylation of the hypoxic inducible transcription factors (HIFs), mediating their hypoxic regulation. Consequently, these hydroxylases are currently being targeted therapeutically to modulate HIF activity in anemia, inflammation, and ischemic disease. Modulating the HIFs by targeting these hydroxylases may result in both desirable and undesirable effects on TRP channel activity, depending on the physiological context. For the best outcomes, these hydroxylases could be therapeutically targeted in pathologies where activation of both the HIFs and the relevant TRP channels are predicted to independently achieve positive outcomes, such as wound healing and obesity.


Rate Adaptive Based Resource Allocation with Proportional Fairness Constraints in OFDMA Systems.
Orthogonal frequency division multiple access (OFDMA), which is widely used in the wireless sensor networks, allows different users to obtain different subcarriers according to their subchannel gains. Therefore, how to assign subcarriers and power to different users to achieve a high system sum rate is an important research area in OFDMA systems. In this paper, the focus of study is on the rate adaptive (RA) based resource allocation with proportional fairness constraints. Since the resource allocation is a NP-hard and non-convex optimization problem, a new efficient resource allocation algorithm ACO-SPA is proposed, which combines ant colony optimization (ACO) and suboptimal power allocation (SPA). To reduce the computational complexity, the optimization problem of resource allocation in OFDMA systems is separated into two steps. For the first one, the ant colony optimization algorithm is performed to solve the subcarrier allocation. Then, the suboptimal power allocation algorithm is developed with strict proportional fairness, and the algorithm is based on the principle that the sums of power and the reciprocal of channel-to-noise ratio for each user in different subchannels are equal. To support it, plenty of simulation results are presented. In contrast with root-finding and linear methods, the proposed method provides better performance in solving the proportional resource allocation problem in OFDMA systems.


Cholesterol-linked fluorescent molecular beacons with enhanced cell permeability.
We appended pyrene units covalently onto adenosine (forming A(P) units) and then incorporated them into oligonucleotides such that they were positioned in complementary locations in opposite strands in the middle positions of hairpin stems. System 1 (A(P)A(P)) behaves as an effective molecular beacon (MB) that changes color from green to blue upon duplex formation. In addition, we attached a cholesterol unit to a free terminus of one of these hairpins; this approach enhanced the cellular delivery of the modified MB relative to those encountered when using conventional transfection methods. These structurally simple cholesterol-based MB systems, which can be synthesized very efficiently, have good potential for opening up new and exciting opportunities in the field of in vivo biosensors.


The determination of defense style by questionnaire.
The Defense Style Questionnaire was relabeled in terms of DSM-III-R defenses and administered to three groups: a normal population, family practice patients, and patients with anxiety disorders. The preferred factor structure identified mature defenses (sublimation, humor, anticipation, and suppression), neurotic defenses (undoing, altruism, idealization, and reaction formation), and immature defenses (projection, passive aggression, acting out, etc). Factor scores varied systematically with group membership and with measures of total symptoms. In this cross-sectional study, the vulnerability factors of neuroticism, locus of control, and defense style were all correlated with neurotic symptoms, but defense style added little to the variance explained by the other two. Within the patient group, however, neuroticism and locus of control did not distinguish among panic disorder, agoraphobia, social phobia, and obsessive-compulsive disorder, while defense style showed patterns characteristic of each disorder.


Effects of hexestrol, medroxyprogesterone acetate and chlormadinone acetate on 7, 12-dimethylbenz [a] anthracene-induced rat mammary cancer in relation to estrogen receptor.
The effects of hexestrol (HXS), medroxyprogesterone acetate (MAP) and chlormadinone acetate (CMA) on 7, 12-dimethylbenz [a] anthracene-induced mammary cancer in rats were evaluated. As a result of successive intramuscular injections of HXS at dosages of 2 or 10 mg/kg or MAP at dosages of 24 or 120 mg/Kg, tumors were markedly reduced in size in all groups on day 7 approximately 14. These effects were the same regardless of the presence or absence of cytoplasmic estrogen receptors (ER) in tumors as determined by the dextran-coated charcoal method. Although such an effect was also seen with CMA, it was much less marked than the effects seen with HXS and MAP. The body weights of HXS-administered groups decreased considerably, whereas those of MAP-administered groups increased. These results may suggest that there is another endocrinological tumor-suppressing mechanism besides the mechanism involving the estrogen-ER system in large-dose administration of HXS and MAP.


Sonographic evaluation of spleen size and prevalence of accessory spleen in a healthy male Turkish population.
It is known that the measurement of splenic length in routine clinical practice is a very good indicator of actual splenic size. Knowledge of the normal range of spleen size in the population being examined is a prerequisite. Racial differences in splenic length could result in incorrect interpretation of splenic measurements. The purpose of this study was to establish the range of spleen length in a young male Turkish population. A total of 2179 volunteers, healthy men aged 17-42 years, from the annual Army Reserve Officer Training Corps training camp at Manisa were included in the study. Sonographic measurements of spleen length were performed on 2179 military personnel. Presence of accessory spleen was also determined. In addition, the height, weight, and age of each volunteer were recorded. Using linear regression analysis, the relation of spleen length and body height, weight and body mass index (BMI) was evaluated. Additionally, the prevalence of accessory spleen detected on ultrasound was calculated. The mean±SD height was 173,1±6,5 cm, mean weight 69,1±9,7 kg, and mean BMI 22,62±2,87. Mean spleen length was 10,76±1,8 cm. The length of the spleen was below 12,80 cm in 95% of the subjects. No statistically significant correlation (p<0.01) between spleen length and body height, weight and BMI was found. The prevalence of accessory spleen was determined as 2.5% on ultrasound screening. It was found that in healthy Turkish men, mean spleen length was 10,76±1,8 cm. This data should be taken into consideration when the diagnosis of splenomegaly is established in Turkish males.


Commentary: A response to Wortzel and Arciniegas about amnesia and crime.
The review by Wortzel and Arciniegas of the phenomenology and neuroanatomy of memory is a welcome complement to our psychiatric clinical perspective on the concept of amnesia in relation to crime. The authors raise their concerns in noting that certain concepts referred to in the literature are inconsistent with the phenomenology and neurobiology of memory. In response, we clarify the DSM-IV-TR nomenclature and provide information on current research exploring various mechanisms outlining memory impairment and other neurocognitive deficits in schizophrenia and other psychoses. In relation to amnesia and crime, the practice of forensic psychiatry requires the expert to be able to consider the validity of amnesia claims in criminal proceedings, translate scientific knowledge into a language accessible to the court, and provide an opinion. As such, a psychiatric clinical approach to the concept of amnesia in relation to crime provides a useful framework.


Unfolded protein response in chronic obstructive pulmonary disease: smoking, aging and disease: a SAD trifecta.
Cigarette smoke (CS) is a risk factor for the development of chronic obstructive pulmonary disease (COPD). Oxidative stress is an immediate result of CS exposure and has the ability to modify cellular proteins. The endoplasmic reticulum (ER) is a compartment where early steps of synthesis and folding of membrane and secretory proteins takes place. Oxidative stress has been shown to interfere with protein folding in the ER and elicits the unfolded protein response (UPR). The UPR is a massive endoplasmic reticulum to the nucleus and the cellular kinase cascades signaling pathway. The UPR triggers a series of intracellular events that aim to help cells overcome the consequences of the stress or eliminate rogue cells by altering expression of genes involved in anti-oxidant defense, cell cycle progression, inflammation, and apoptosis. Recent data demonstrate that CS induces the UPR in vitro and in vivo. The timing of UPR induction in smokers and the mechanism of CS-induced UPR are areas of active investigation. The role of UPR in the protection of smoker's lungs from CS-induced oxidative stress, and its contribution to CS-induced apoptosis and inflammation, is beginning to emerge. This review discusses recent data about UPR in COPD and summarizes findings on UPR that have potential relevance to COPD.


Study on the Increased Probability of Detecting Adverse Drug Reactions Based on Bayes' Theorem: Evaluation of the Usefulness of Information on the Onset Timing of Adverse Drug Reactions.
In order to avoid adverse drug reactions (ADRs), pharmacists are reconstructing ADR-related information based on various types of data gathered from patients, and then providing this information to patients. Among the data provided to patients is the time-to-onset of ADRs after starting the medication (i.e., ADR onset timing information). However, a quantitative evaluation of the effect of onset timing information offered by pharmacists on the probability of ADRs occurring in patients receiving this information has not been reported to date. In this study, we extracted 40 ADR-drug combinations from the data in the Japanese Adverse Drug Event Report database. By applying Bayes' theorem to these combinations, we quantitatively evaluated the usefulness of onset timing information as an ADR detection predictor. As a result, when information on days after taking medication was added, 54 ADR-drug combinations showed a likelihood ratio (LR) in excess of 2. In particular, when considering the ADR-drug combination of anaphylactic shock with levofloxacin or loxoprofen, the number of days elapsed between start of medication and the onset of the ADR was 0, which corresponded to increased likelihood ratios (LRs) of 138.7301 or 58.4516, respectively. When information from 1-7 d after starting medication was added to the combination of liver disorder and acetaminophen, the LR was 11.1775. The results of this study indicate the clinical usefulness of offering information on ADR onset timing.


An introduction to Staphylococcus aureus, and techniques for identifying and quantifying S. aureus adhesins in relation to adhesion to biomaterials: review.
The ability of Staphylococcus aureus to adhere to the extracellular matrix and plasma proteins deposited on biomaterials is a significant factor in the pathogenesis of orthopaedic-device related infections. S. aureus possesses many adhesion proteins on its surface, but it is not known how they interact with each other to form stable interactions with the substrate. A novel method was developed for extracting adhesins from the S. aureus cell wall, which could then be further analysed. The protocol involves using a FastPrep instrument to mechanically disrupt the cell walls resulting in native cell walls. Ionically and covalently bound proteins were then solubilised using sodium dodecyl sulphate (SDS) and lysostaphin, respectively. Western blot analysis of covalently bound proteins using anti-protein A and anti-clumping factor A sera showed that S. aureus produces most surface proteins in early growth, and less in post-exponential and stationary growth. Immuno-gold labelling of protein A, and clumping factor A was observed all over the bacteria and showed no distinct surface distribution pattern. However, this labelling showed expression of surface associated proteins varied in a growth-phase dependent and cell-density dependent manner.


Investigation into pyruvate kinases from Escherichia coli K-12 grown under aerobic and anaerobic conditions.
Two forms of anaerobic Escherichia coli K-12 pyruvate kinase (EC 22.214.171.124) were separated by ammonium sulphate fractionations. Pyruvate kinases I is allosteric and pyruvate kinase II is non-allosteric to phosphoenolpyruvate. The addition of 1 mM FDP reversed the allostery to normal Michaelis-Menten kinetics. AMP had no effect, whereas 8 mM ATP completely inhibited the enzyme. The enzyme showed normal kinetics with ADP as substrate. Mg2+ and Mn2+ stimulated whereas Cu2+ severely inhibited the enzyme, which could be reversed by the addition of 1 mM FDP. Citrate, alpha-ketoglutarate, succinate, fumarate and alanine inhibited the enzyme, whereas phenylalanine had no effect. The allosteric pyruvate kinase from aerobic cultures was not only activated by FDP, but also by AMP. FDP changed Km and Vmax, whereas AMP influenced only the Km. During aerobic-anaerobic transition, pyruvate kinase synthesis increases and reaches a maximum under anaerobic conditions. The degree of FDP activation remains constant, but AMP activation is lost during transition. Aerobic cultures of E. coli K-12 grown on gluconeogenic substrates exhibited pyruvate kinase II activity (non-allosteric), which was stimulated by FDP and by AMP. It has been suggested that E. coli may have two types of pyruvate kinase II depending on the substrate and two types of pyruvate kinase I depending on oxygen tension in the medium.


Constitutively CD40-activated B cells regulate CD8 T cell inflammatory response by IL-10 induction.
B cells are exposed to high levels of CD40 ligand (CD40L, CD154) in chronic inflammatory diseases. In addition, B cells expressing both CD40 and CD40L have been identified in human diseases such as autoimmune diseases and lymphoma. However, how such constitutively CD40-activated B cells under inflammation may impact on T cell response remains unknown. Using a mouse model in which B cells express a CD40L transgene (CD40LTg) and receive autocrine CD40/CD40L signaling, we show that CD40LTg B cells stimulated memory-like CD4 and CD8 T cells to express IL-10. This IL-10 expression by CD8 T cells was dependent on IFN-I and programmed cell death protein 1, and was critical for CD8 T cells to counterregulate their overactivation. Furthermore, adoptive transfer of naive CD8 T cells in RAG-1(-/-) mice normally induces colitis in association with IL-17 and IFN-γ cytokine production. Using this model, we show that adoptive cotransfer of CD40LTg B cells, but not wild-type B cells, significantly reduced IL-17 response and regulated colitis in association with IL-10 induction in CD8 T cells. Thus, B cells expressing CD40L can be a therapeutic goal to regulate inflammatory CD8 T cell response by IL-10 induction.


Analysis of the Generation of Vibration Signals under Uniaxial Loading of Materials Using the Coherent Properties of Laser Radiation.
: The present article describes the results of theoretical and experimental investigations of the force response of materials to external tensile stresses. The method used is based on remote precision measurements of the amplitudes of the harmonics of vibration signals and synchronous fixation of deformations under load. It was determined that the shape of the propagating acoustic signal depends not only on the bias time, but also on the frequency. In addition, fixation of the moments of occurrence of the vibrational signals and determination of the number of excesses in the amplitudes of harmonics over the discrimination level allows structural models to be studied in order to diagnose the strength properties of materials under dynamic loading of solids. The experimental setup consisted of a P100 Labtest-2 tearing machine providing a loading speed of 6.22 mm/min, a Polytech PSV-400 vibrometer including lasers, and a computer. Measurements were made at frequencies of 0.4, 1.6, and 40 kHz. An analysis of the mathematical models of the occurrence and propagation of acoustic signals in a material under load is presented, and the features of their application are reported. Transferring the moments of occurrence of vibrational signals to a strain diagram from the applied load allows the development of physical processes of hardening and destruction of materials to be traced. The occurrence of vibrational signals under load can be used as an information parameter for the diagnosis of developing defects in the structure of materials under load.


Pancreatitis in children: clinical analysis of 61 cases in southern Taiwan.
The purpose of this study was to analyze the characteristics of the clinical presentations, etiologies, diagnoses, and treatment of pediatric pancreatitis in southern Taiwan. Sixty-one patients, ranging in age from 2 to 18 years (mean, 8.8+/-4.8 years old), with diagnoses of pancreatitis were studied from July 1986 through June 2000. Twenty-eight pancreatitis cases resulted from physical trauma, 13 cases of which were from traffic accident (53.8% from motorcycle accident). Other pathogenic factors included systemic diseases (N=9), pancreaticobiliary-tree anomalies (N=7), toxin ingestion or drug use (N=4), Ascaris infection (N=1), and idiopathic (N=12). Symptoms included abdominal pain (N=58), vomiting (N=23), fever (N=18), and jaundice (N=2). Hyperamylasemia was found in 51 children (83.6%). Twenty-seven patients (90.0%) had elevated serum lipase levels (>190 U/L) of 30 evaluated. The amylase to creatinine clearance ratio was assayed for 35 cases, of which 28 (80.0%) were elevated (>6%). Ultrasonography revealed inflammatory changes of the pancreas in 40 of 51 patients evaluated, while computed tomogram demonstrated evidence of pancreatic inflammation for all 21 patients evaluated. Fifteen cases required surgery, while the other 46 were managed conservatively. One patient died because of acute necrotizing pancreatitis 3 days after L-asparaginase treatment for leukemia. The other patients survived well during long-term follow up. Pancreatitis in children is more common than generally believed. Physical trauma, especially because of motorcycle accidents, was the leading cause of pediatric pancreatitis in southern Taiwan. The mortality rate was low. Only one patient who had undergone chemotherapy with L-asparaginase died of the disease.


Dry eye disease among patients infected with the SARS-CoV-2 Omicron variant: a cross-sectional study.
To investigate the incidence of dry eye disease (DED) and relevant risk factors among patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant. This cross-sectional, observational analysis included 993 patients with corona virus disease 2019 (COVID-19) treated at the National Exhibition and Convention Center (Shanghai) Fangcang Shelter Hospital, from April 10 to May 26, 2022. Totally 944 uninfected control participants were recruited. All participants completed ocular surface disease index (OSDI) questionnaires, and DED symptoms were determined using OSDI scores. The demographic characteristics, length of hospital stay and in nasopharyngeal swabs were performed using questionnaires. SARS-CoV-2 Omicron variant infection was confirmed by nucleic acid-based detection in nasopharyngeal swabs using a 2019-nCoV nucleic acid detection kit. The risk factors for DED symptoms among patients with COVID-19 and control participants were determined by logistic regression analysis. Patients with COVID-19 showed a higher incidence of DED than controls (64.9% vs 55.1%, P<0.001). SARS-CoV-2 infection [odds ratios (ORs) (95%CI): 1.271 (1.038, 1.556)], use of contact lenses [ORs (95%CI): 9.350 (3.676, 23.783)], history of corneal refractive surgery [ORs (95%CI): 2.047 (1.494, 2.804)], poor sleep quality [ORs (95%CI): 2.657 (2.029, 3.480)], and video display terminal (VDT) use for more than 8h per day [ORs (95%CI): 6.348 (4.720, 8.538)] were found to be risk factors for DED symptoms in patients with COVID-19 as well as controls. For patients with COVID-19, the length of hospital stay [ORs (95%CI): 1.196 (1.134, 1.262)], use of contact lenses [ORs (95%CI): 20.423 (2.680, 155.632)], history of corneal refractive surgery [ORs (95%CI): 2.166 (1.321, 3.553)], poor sleep quality [ORs (95%CI): 3.650 (2.381, 5.597)], and VDT use for more than 8h per day [ORs (95%CI): 7.740 (4.918, 12.180)] were significant risk factors for DED symptoms. Patients with COVID-19 are more prone to develop symptomatic DED. SARS-CoV-2 infection and length of hospital stay are important risk factors for DED symptoms.


Follow-up of a new titanium cervical plate for fusion of the cervical spine.
Cervical plates are in use since the 1990ies for anterior cervical discectomy and fusion (ACDF). The latest step in development was a dynamic plate that allows sliding of the screws facilitating the natural settling of the bone after surgery. We investigated the clinical and radiological results of such a dynamic plate in a patient cohort that underwent single or multi-level ACDF for various cervical degenerative indications, including revision cases, from 2014 to 2019. Clinical and radiological outcome were assessed in 60 eligible patients after a mean of 2.9 years. The assessed neck disability index (NDI), and the visual analogue scale (VAS) of neck and arm pain show comparable results to the literature of ACDF, and specifically other plate designs. Forty-eight Adverse and Serious Adverse Events do not show a link to the product used. Clinical and radiological outcomes of ACDF with dynamic, third generation cervical plates show comparable results to the literature. Careful reporting of all Adverse Events revealed a variety of concomitant diseases, but could not be correlated to the implant used.


Malocclusion and temporomandibular disorder: a comparison of adolescents with moderate to severe dysfunction with those without signs and symptoms of temporomandibular disorder and their further development to 30 years of age.
A total of 1018 subjects were examined at the age of 11 years, 791 were reexamined at 15 years, 456 at 19 years, and 337 at 30 years. Anamnestic and clinical recordings of temporomandibular disorder (TMD) were made. Morphology, including calculation of peer assessment rating (PAR) scores, was recorded. Previous history of orthodontic treatment was assessed. Muscular endurance was recorded. The subjects completed four psychological measures. The malocclusion prevalence, occlusal contacts, psychological factors, and muscular endurance in subjects with no recorded signs and symptoms of TMD were compared with those with the most severe dysfunction at 19 years of age. The further development of TMD to 30 years of age was followed. PAR scores were significantly higher in the subjects with the most severe dysfunction. Apart from crowding of teeth, no other significant differences were found between the groups with regard to separate malocclusions, tooth contact pattern, orthodontic treatment, or extractions. A greater proportion of subjects with low endurance were found in those with TMD. Significant associations between TMD and general health and psychological well-being as well as the personality dimension of neuroticism and self-esteem were found. During the period from 19 to 30 years, the prevalence of muscular signs and symptoms showed considerable reduction, whereas clicking showed a slight increase. Locking of the joint showed a decrease from 19 to 30 years. One-quarter of the TMD subjects showed complete recovery. Thus, orthodontic treatment seems to be neither a major preventive nor a significant cause of TMD.


A screening programme on chronic solvent-induced encephalopathy among Dutch painters.
Long-term exposure to organic solvents may lead to chronic solvent induced encephalopathy (CSE) in painters. In combination with reduction of exposure, a workers' health surveillance programme was developed, resulting in a three-stage CSE screening procedure for early neurobehavioural changes possibly predicting chronic health effects. The screening consists of a questionnaire (Neurosymptom Screening Checklist 60, NSC-60), computerised neurobehavioural functioning testing (Neurobehavioural Evaluation System; NES2) and multidisciplinary differential diagnostic evaluation by experts (called 'Solvent Team'). Results from the screening were compared with the results of the 'care as usual' (CAU), in which symptomatic patients were referred directly to the Solvent Team by occupational physicians, general practitioners or medical specialists. Parallel to the screening programme, a legal ban on indoor use of solvent-based paints resulted in lower exposure to solvents. To investigate the usefulness of the NSC-60 questionnaire as a screening tool for CSE among painters and to investigate the course of the number of CSE cases over the years as a potential consequence of improved prevention and control. From 1998 to 2004, more than 40,000 painters were invited to participate in a health surveillance programme including a periodical occupational health examination (PHE) and 50% did participate. Four percent (N=794) of these had a positive score on the NSC-60. The Solvent Team assessed 101 of these for CSE, which resulted in 27 CSE cases diagnosed. CAU during the same period of the surveillance (1998-2004) yielded 619 painters and 75 of these had the diagnosis CSE. After 2002 the number of CSE diagnosed cases dropped considerably and in 2004 only one case of CSE could be diagnosed. The substantially lower prevalence of CSE diagnosed cases in painters after 2002 might partly be explained as a result of a successful participation in the screening procedure of most prevalent CSE cases during the years 1998-2002. A second reason for the reduction of new diagnosed cases of CSE can be the effectiveness of the ban on indoor use of solvent-based paints resulting in lower exposure levels at work. The screening procedure is useful to screen for CSE among people taking part in the PHE programme. Control of CSE can be achieved by an integrated preventive approach with reduction of exposure and screening on early health effects.


Cofactor engineering improved CALB production in Pichia pastoris through heterologous expression of NADH oxidase and adenylate kinase.
The cofactor engineering strategy can relieve the metabolic stress induced by expression of recombinant protein in cellular metabolism related to cofactor and energy reactions. To study the effect of cofactor regeneration on recombinant protein expression, NADH oxidase (noxE) was engineered in P. pastoris expressing lipase B (GSCALB). Expression of noxE in P. pastoris (GSCALBNOX) increased NAD+ levels by 85% with a concomitant reduction in NADH/NAD+ ratio of 67% compared to GSCALB. The change in the redox level positively influenced the methanol uptake rate and made 34% augment in CALB activity. The decline in NADH level (44%) by noxE expression had lowered the adenylate energy charge (AEC) and ATP level in GSCALBNOX. In order to regenerate ATP in GSCALBNOX, adenylate kinase (ADK1) gene from S. cerevisiae S288c was co-expressed. Expression of ADK1 showed a remarkable increase in AEC and co-expression of both the genes synergistically improved CALB activity. This study shows the importance of maintenance of cellular redox homeostasis and adenylate energy charge during recombinant CALB expression in P. pastoris.


Prediction of meatiness and fatness in ducks by using a skin slice with subcutaneous fat and carcass weight without skin.
The experiment was performed on Pekin ducks (A-44 strain; 60 males and 60 females). The birds were reared to 7 wk of age and fed standard diets ad libitum. At the completion of the rearing period, the ducks were killed. The carcasses were chilled, and skin slices with s.c. fat were removed by a new method. The remaining part of the carcass was dissected into meat, intermuscular fat, and bones. The statistical analysis showed that the weight of a skin slice with s.c. fat, taken from the carcass surface excluding the forearms and wing tips [skin slice with fat (X(2))], and the weight of a carcass without this slice, forearms, and wing tips (X(1)) were very good indicators of the content of skin with fat (r = 0.99) and meat (r = 0.96), respectively, in a whole carcass. The above traits provided the basis for deriving regression equations to estimate the content of meat (Y) or skin with s.c. and intermuscular fat (U) in whole carcasses of ducks. The following 2 equations may be recommended for practical application: Y = 0.691 X(1) - 0.77 (S(y) = 21.6 g) U = 1.056 X(2) + 53.32 (S(u) = 10.6 g).


Probable and possible transfusion-transmitted dengue associated with NS1 antigen-negative but RNA confirmed-positive red blood cells.
In the absence of active blood donation screening, dengue viruses (DENV) have been implicated in only a limited number of transfusion transmissions worldwide. This study attempted to identify if blood from donors testing negative by an NS1-antigen (Ag) enzyme-linked immunosorbent assay (ELISA) but confirmed positive for DENV RNA caused DENV-related disease in recipients during the epidemic years of 2010 to 2012 in Puerto Rico. Donation aliquots testing negative by an investigational NS1-Ag ELISA were stored frozen and retested retrospectively using a research transcription-mediated amplification assay (TMA) detecting DENV RNA. All RNA-reactive donations were subject to confirmatory RNA and antibody testing. Recipient tracing was conducted for all components manufactured from TMA-reactive components. Medical chart review, recipient interview, and follow-up sampling occurred for 42 recipients transfused with TMA-reactive components. Six of 42 recipients developed new-onset fever in the 2 weeks posttransfusion; three (50%) received RNA confirmed-positive, NS1-Ag-negative red blood cell (RBC) units. One recipient of a high-titer unit (7 × 10(7) DENV-4 RNA copies/mL) developed severe dengue, and a second recipient had only fever recorded but had a negative sepsis work-up. New fever attributable to DENV infection in a third recipient was confounded by fever potentially attributable to posttransfusion sepsis. In our retrospective study, NS1-Ag detected 20% of all RNA confirmed-positive donations demonstrating limitations of NS1-Ag ELISA for blood donation screening. We identified one recipient with a clinical syndrome compatible with severe dengue who had received an NS1-Ag-negative but RNA confirmed-positive RBC unit. This investigation illustrates the difficulty in confirming transfusion transmission in dengue-endemic areas among severely ill transfusion recipients.


Analysis of the risk reduction of prophylactic partial mastectomy in Sprague-Dawley rats with 7,12-dimethylbenzanthracene-induced breast cancer.
The effectiveness of prophylactic mastectomy in preventing breast cancer was studied in female albino Sprague-Dawley rats. Group A served as untreated controls. Groups B, C, and D underwent 50%, 75%, and total mastectomies 2 weeks after the administration of 7,12-dimethylbenzanthracene (DMBA). Group E was initially subjected to total mastectomy. Two weeks after surgery, group E received 5 mg of DMBA intravenously. Group F underwent sham procedures. All animals were sacrificed at age 8 months. The mean number of tumors per animal developing in groups A through E was 5.00, 5.17, 4.67, 5.46, and 5.20, respectively. There was 0.21 tumor per animal in group F. The mean time to tumor development in groups A through E was 11.33, 10.05, 9.88, 19.25, and 19.38 weeks, respectively. All results were subjected to an analysis of variance. There was no statistically significant difference in the number of DMBA-induced tumors in groups A through E. Groups D and E had a significant prolonged time to tumor development. The overall risk of the development of breast tumors was not significantly reduced by prophylactic mastectomy. Residual breast tissue after prophylactic mastectomy is at increased risk for the development of breast tumors. The risk of developing breast tumors in this model is not reduced in proportion to the amount of breast tissue removed. (This study suggests that subcutaneous mastectomy in high-risk individuals may not have appropriate prophylaxis against the development of carcinoma of the breast.)


New technologies for the assessment of neuropathies.
Technical advances are rapidly changing the clinical and instrumental approach to peripheral nerve diseases. Magnetic resonance neurography, diffusion tensor imaging and nerve ultrasonography are increasingly entering the diagnostic workup of peripheral neuropathies as tools that complement neurophysiology and enable investigation of proximal structures, such as plexuses and roots. Progress in the design of magnetic resonance scanners and sequences, and the development of high-frequency ultrasound probes mean that high-resolution peripheral nerve imaging is possible, enabling detailed examination of nerve size, morphology and internal fascicular structure that can integrate nerve conduction studies into clinical practice. In the growing field of small-fibre neuropathy, in which traditional nerve conduction studies are of little or no use, skin biopsy has become a reliable tool for diagnosis. Corneal confocal microscopy, nociceptive evoked potentials and microneurography are emerging techniques that are mainly used in clinical research settings, but have increasing relevance to clinical practice. We review these new and emerging techniques and their effects on diagnosis, treatment strategies and prognosis in a variety of peripheral neuropathies, including entrapments, brachial plexopathies, immune and inherited neuropathies, and small-fibre neuropathies. We discuss the most promising research findings and their potential for future application in clinical practice.


Predicted Lifetime Health Outcomes for Aducanumab in Patients with Early Alzheimer's Disease.
Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disease that places a substantial burden on patients and caregivers. Aducanumab is the first AD therapy approved by the US Food and Drug Administration to reduce a defining pathophysiological feature of the disease, brain amyloid plaques. In the phase 3 clinical trial EMERGE (NCT02484547), aducanumab reduced clinical decline in patients with mild cognitive impairment (MCI) due to AD and mild AD dementia and confirmed amyloid pathology. We used a Markov modeling approach to predict the long-term clinical benefits of aducanumab for patients with early AD based on EMERGE efficacy data. In the model, patients could transition between AD severity levels (MCI due to AD; mild, moderate, and severe AD dementia) and care settings (community vs. institution) or transition to death. The intervention was aducanumab added to standard of care (SOC), and the comparator was SOC alone. Data sources for base-case and scenario analyses included EMERGE, published National Alzheimer's Coordinating Center analyses, and other published literature. Per patient over a lifetime horizon, aducanumab treatment corresponded to 0.65 incremental patient quality-adjusted life-years (QALYs) and 0.09 fewer caregiver QALYs lost compared with patients treated with SOC. Aducanumab treatment translated to a lower lifetime probability of transitioning to AD dementia, a lower lifetime probability of transitioning to institutionalization (25.2% vs. 29.4%), delays in the median time to transition to AD dementia (7.50 vs. 4.92 years from MCI to moderate AD dementia or worse), and an incremental median time in the community of 1.32 years compared with SOC. The model predicted long-term benefits of aducanumab treatment in patients with MCI due to AD and mild AD dementia and their caregivers. The predicted outcomes provide a foundation for healthcare decision-makers and policymakers to understand the potential clinical and socioeconomic value of aducanumab.


RNA editing independently occurs at three mir-376a-1 sites and may compromise the stability of the microRNA hairpin.
RNA editing is being recognized as an important post-transcriptional mechanism that may have crucial roles in introducing genetic variation and phenotypic diversity. Despite microRNA editing recurrence, defining its biological relevance is still under extended debate. To better understand microRNA editing function and regulation we performed an exhaustive characterization of the A-to-I site-specific patterns in mir-376a-1, a mammalian microRNA which RNA editing is involved in the regulation of development and in disease. Thorough an integrative approach based on high-throughput small RNA sequencing, Sanger sequencing and computer simulations we explored mir-376a-1 editing in samples from various individuals and primate species including human placenta and macaque, gorilla, chimpanzee and human brain cortex. We observed that mir-376a-1 editing is a common phenomenon in the mature and primary microRNA molecules and it is more frequently detected in brain than in placenta. Primary mir-376a-1 is edited at three positions, -1, +4 and +44. Editing frequency estimations and in silico simulations indicated that editing was not equally recurrent along the three mir-376a-1 sites, nevertheless no epistatic interactions among them were observed. Particularly, the +4 site, located in the seed region of the mature miR-376a-5p, reached the highest editing frequency in all samples. Secondary structure predictions revealed that the +4 position was the one that conferred the highest stability to the mir-376a-1 hairpin. We suggest that molecular stability might partially explain the editing recurrence observed in certain microRNAs and that editing events conferring new functional regulatory roles in particular tissues and species could have been conserved along evolution, as it might be the case of mir-376a-1 in primate brain cortex.


Sources of contraceptive commodities for users in Nigeria.
Understanding the sources of contraceptive commodities is an important aspect of the delivery of family planning services and is required by planning programme managers for strategic planning purposes. Findings from the 2003 Nigeria Demographic and Health Survey have previously showed that the private sector was the most frequently reported source of contraceptive supply, providing contraception to two and a half times as many women as the public sector. We conducted a community-based study to examine further the sources of contraceptive commodity for users in Nigeria with a view to identifying their preferences for distribution centres. This information would be useful to improve commodity distribution and to build the necessary capacity for satisfactory delivery of contraceptives. A multi-stage random sampling technique was used. A state was randomly selected to represent each of the four health zones in Nigeria. Two local government areas (LGAs) were then selected representing both urban and rural areas. Ten enumeration areas were subsequently selected from each LGA. Of the 2,001 respondents aged 15-49 years, 1,647 (82.3%) were sexually active, out of which 244 were found to be using contraceptive methods at the time of the study, giving a contraceptive prevalence of 14.8%. The commonest source of information on contraceptives was through friends (34%), followed by the radio (11.5%) and husbands (10.2%). Most respondents procured their contraceptives from chemist/patent medicine shops (19.7%), while only 0.8% obtained them from designated family planning clinics. The younger groups in this study (15-24 years), single people, Catholics, and Muslims, showed a greater preference for chemist/patent medicine shops for their sources of contraceptives. The older groups and married respondents, however, made use of government and private hospitals to obtain their contraceptives. Strategies to increase contraceptive use must take into consideration these identified sources of contraceptives with a view to enhancing the quality, quantity, and variety of methods available, and to building capacity for effective service delivery. There is also a need to encourage the establishment of adolescent-friendly clinics where young people can go for counselling and obtain contraceptives of their choice, including emergency contraceptive pills.


SLE and pregnancy.
In patients with SLE in remission pregnancy does not confer a special risk to either the mother or foetus, and immunoregulatory drugs should not be withdrawn prior to a pregnancy where these are required for disease control. Likewise therapy to treat disease flares during pregnancy should not be withheld as the foetus is at comparitively more risk from the effects of the maternal disease than from the small risk associated with therapy. Patients with active disease should be counselled against pregnancy but therapeutic abortion in such patients is only very rarely indicated. High risk groups benefit from close monitoring though the previous obstetric history will not necessarily reflect outcome in subsequent pregnancies. Patients without a previous obstetric history should not be treated prophylactically due to the detection of antiphospholipid antibodies, and the optimum treatment for those with poor histories and aPL is currently being investigated.


Dynein-independent functions of DYNLL1/LC8: redox state sensing and transcriptional control.
The highly conserved DYNLL/LC8 proteins promote dimerization of a broad range of targets and are essential for the integrity, activity, or both, of many subcellular systems, such as dyneins, myosin V, and apoptotic factors. Defects in DYNLL/LC8 function lead to severe cellular and developmental phenotypes in multicellular organisms, whereas loss-of-function alleles are lethal. DYNLL/LC8 dimer formation may be controlled by various signaling inputs (including pH changes and phosphorylation), and dimerization has been linked to alterations in the enzymatic activity of neuronal nitric oxide synthase and apoptotic control. A recent report now proposes that DYNLL/LC8-driven interactions are also regulated by changes in cellular redox state, which lead to intermonomer disulfide bond formation and ultimately activation of the transcription factor NF-kappaB.


Efficacy comparison of 21 interventions to prevent retinopathy of prematurity: a Bayesian network meta-analysis of randomized controlled trials.
The objective of this study was to evaluate the comparative efficacy of current interventions for the prevention of retinopathy of prematurity (ROP) in premature infants. A network meta-analysis (NMA) was performed. We searched PubMed, Web of Science, Scopus, Embase, and the Cochrane Library for relevant studies from their inception to May 5, 2022. Publications were eligible for our study if they were randomized controlled trials (RCTs) involving preterm infants at <37 weeks of gestational age and reported the incidence of any-stage ROP treated with the interventions of interest. The overall effect was pooled using the random effects model. We identified 106 RCTs (involving 23894 participants). This NMA showed that vitamin A supplementation markedly reduced the incidence of ROP, in comparison with placebo (odds ratio [OR] = 0.59, 95% credible interval [95% CrI] 0.33, 0.85), fish oil-based lipid emulsion (OR = 0.57, 95% CrI 0.24, 0.90), early erythropoietin (OR = 0.51, 95% CrI 0.34, 0.98), probiotics (OR = 0.48, 95% CrI 0.32, 0.97), and human milk (OR = 0.50, 95% CrI 0.21, 0.78). Vitamin A supplementation has the highest probability of being the best option for reducing the ROP risk compared with the other 20 interventions based on its surface under the cumulative ranking curve (SUCRA) value (SUCRA = 92.50%, 95% CrI 0.71, 1.00). Our findings suggest that among 21 interventions, vitamin A supplementation might be the best method of preventing ROP. This NMA offers an important resource for further efforts to develop preventive strategies for ROP.


Short-term effects of maternal oxygen administration on blood flow velocity waveforms in healthy and growth-retarded fetuses.
To determine whether maternal oxygen administration affects fetal hemodynamics, we investigated 10 healthy fetuses and 10 growth-retarded fetuses near term by means of Doppler ultrasonography. The growth-retarded fetuses were characterized by abnormal blood flow velocity waveforms. Velocity waveforms were simultaneously recorded at 5-minute intervals from the fetal descending aorta and internal carotid artery before, during, and after maternal oxygen administered through a face mask that delivered 60% oxygen. The pulsatility index was calculated. During oxygen treatment growth-retarded fetuses showed significant temporary hemodynamic modifications as expressed by changes of pulsatility index values that increased in the internal carotid artery and decreased at the level of the descending aorta. On the other side no changes were found in healthy fetuses. These findings suggest that maternal oxygen administration can modify fetal hemodynamics in cases of growth retardation associated with abnormal blood flow velocity waveforms.


[Expression of programmed death 1 and its ligands in iris-ciliary body from mice with anterior chamber-associated immune deviation].
To study the expression and possible implication of programmed death 1 (PD-1) and its ligands in the iris-ciliary body from mice with anterior chamber-associated immune deviation (ACAID). This was an experimental study. Twenty-four BALB/c mice were divided into ACAID group, negative controls, positive controls and phosphate-buffer saline controls. ACAID was evaluated by delayed-type hypersensitivity response. Expressions of PD-1 and its ligands (PD-L1, PD-L2) in the iris-ciliary body from ACAID mice were determined by real-time polymerase chain reaction and immunohistochemical studies. Delayed-type hypersensitivity was not detected in ACAID group, indicating that ACAID was induced successfully. The expression of PD-1 mRNA in ACAID group was higher than that in all other groups (F = 248. 109, P < 0.05). The positive controls showed a high expression of PD-L1 mRNA (F = 179. 033, P < 0.05). PD-1 and PD-L1 positive cells with round or oval shapes were found in whole iris-ciliary body, especially in the iris base and pupil margin. Expression of PD-1 and PD-L1 proteins were similar to their expression at mRNA levels. Neither mRNA nor protein of PD-L2 was detected in the iris-ciliary body in all groups. An increased expression of PD-1 in the iris-ciliary body of ACAID mice indicates that this is involved in the induction of ACAID.


Contralateral projections of thoracic respiratory interneurones in the cat.
1. Retrograde neuronal transport following small iontophoretic injections of horseradish peroxidase was used to investigate the location of neurones projecting to the thoracic ventral horn of the cat. 2. A concentration of labelled neurones was seen in the contralateral medial ventral horn at the immediately opposite rostrocaudal position. 3. The participation of respiratory interneurones in the projection was investigated by means of spike-triggered averaging, as follows. 4. Spike trains of single interneurones whose firing patterns were related to the central respiratory cycle were recorded extracellularly in the thoracic ventral horn of anaesthetized, paralysed cats. Firing patterns were defined by the construction of cycle-triggered histograms. 5. Spike-triggered averaging of the signal from an extracellular tungsten microelectrode in the opposite ventral horn was performed to test for the presence of axonal, terminal or focal synaptic potentials. 6. At least one of these types of potential was found for 34/55 units. Terminal potentials were found for thirty-one units, accompanied by focal synaptic potentials for twenty-seven units. Potentials were found for units with all types of firing patterns. Units whose activity elicited these potentials were generally located in the medial half of the ventral horn. 7. We conclude that at least 60% of the respiratory interneurones project to the immediately opposite ventral horn.


Quality Indicators for Adolescents and Young Adults With Advanced Cancer: A Modified Delphi Process With Patients, Family Members, and Clinicians.
Quality measures have been devised for end-of-life care of older adults with cancer, but are lacking for adolescents and young adults (AYAs). We previously conducted interviews with AYAs, family caregivers, and clinicians to identify priority domains for high quality care of AYAs with advanced cancer. The goal of this study was to use a modified Delphi process to form consensus around the highest priority quality indicators. A modified Delphi process was conducted with 10 AYAs with recurrent or metastatic cancer, 11 family caregivers, and 29 multidisciplinary clinicians, using small group web conferences. Participants were asked to rate the importance of each of 41 potential quality indicators, rank the 10 most important, and engage in discussion to reconcile differences. Of 41 initial indicators, 34 were rated as highly important (rating seven, eight, or nine on a nine-point scale) by >70% of participants. The panel was unable to reach consensus around the 10 most important indicators. Instead, participants recommended retaining a larger set of indicators to reflect potential for different priorities across the population, resulting in a final set of 32 indicators. Recommended indicators broadly encompassed attention to physical symptoms; quality of life; psychosocial, and spiritual care; communication and decision-making; relationships with clinicians; care and treatment; and independence. A patient- and family-centered process for quality indicator development led to strong endorsement of multiple potential indicators by Delphi participants. Further validation and refinement will be performed using a survey of bereaved family members.


Dual Actions of Mammalian and Piscine Gonadotropin-Inhibitory Hormones, RFamide-Related Peptides and LPXRFamide Peptides, in the Hypothalamic-Pituitary-Gonadal Axis.
Gonadotropin-inhibitory hormone (GnIH) is a hypothalamic neuropeptide that decreases gonadotropin synthesis and release by directly acting on the gonadotrope or by decreasing the activity of gonadotropin-releasing hormone (GnRH) neurons. GnIH is also called RFamide-related peptide in mammals or LPXRFamide peptide in fishes due to its characteristic C-terminal structure. The primary receptor for GnIH is GPR147 that inhibits cAMP production in target cells. Although most of the studies in mammals, birds, and fish have shown the inhibitory action of GnIH in the hypothalamic-pituitary-gonadal (HPG) axis, several in vivo studies in mammals and many in vivo and in vitro studies in fish have shown its stimulatory action. In mouse, although the firing rate of the majority of GnRH neurons is decreased, a small population of GnRH neurons is stimulated by GnIH. In hamsters, GnIH inhibits luteinizing hormone (LH) release in the breeding season when their endogenous LH level is high but stimulates LH release in non-breeding season when their LH level is basal. Besides different effects of GnIH on the HPG axis depending on the reproductive stages in fish, higher concentration or longer duration of GnIH administration can stimulate their HPG axis. These results suggest that GnIH action in the HPG axis is modulated by sex-steroid concentration, the action of neuroestrogen synthesized by the activity of aromatase stimulated by GnIH, estrogen membrane receptor, heteromerization and internalization of GnIH, GnRH, and estrogen membrane receptors. The inhibitory and stimulatory action of GnIH in the HPG axis may have a physiological role to maintain reproductive homeostasis according to developmental and reproductive stages.


The sphingosine 1-phosphate breakdown product, (2E)-hexadecenal, forms protein adducts and glutathione conjugates in vitro.
Sphingosine 1-phosphate (S1P), a bioactive lipid involved in various physiological processes such as cell proliferation and apoptosis, can be irreversibly cleaved by S1P lyase, yielding phosphoethanolamine and (2E)-hexadecenal (2EHD). The latter metabolite, an α,β-unsaturated fatty aldehyde, may be susceptible to nucleophilic attack by cellular biomolecules. Hence, we studied whether 2EHD forms reaction products with GSH and proteins in vitro. Using LC-MS/MS and stable isotopically labeled reference material, we identified a total of nine novel reaction products of 2EHD in a cell-free approach: two GSH conjugates and seven l-amino acid adducts. Both GSH conjugates were also found in HepG2 cell lysates incubated with 2EHD. Likewise, we detected four out of seven amino acid adducts released from the model protein, BSA, and proteins extracted from HepG2 cells. On this occasion, the 2EHD Michael adduct with l-histidine proved to be the most prominent adduct. Most interestingly, inhibition of the enzymatically driven oxidative degradation of 2EHD resulted in increased levels of both GSH conjugates and protein adducts in HepG2 cell lysates. Hence, our data provide new insights into sphingolipid metabolism and will be useful to investigate certain disorders linked to an impaired fatty aldehyde metabolism in more detail.


Sociodemographic and environmental factors associated with dengue, Zika, and chikungunya among adolescents from two Brazilian capitals.
Among the emerging and reemerging arboviral diseases, Zika, dengue and chikungunya deserve special attention due to their wide geographical distribution and clinical severity. The three arboviruses are transmitted by the same vector and can present similar clinical syndromes, bringing challenges to their identification and register. Demographic characteristics and individual and contextual social factors have been associated with the three arboviral diseases. However, little is known about such associations among adolescents, whose relationships with the social environment are different from those of adult populations, implying potentially different places, types, and degrees of exposure to the vector, particularly in the school context. This study aims to identify sociodemographic and environmental risk factors for the occurrence of Zika, dengue, and chikungunya in a cohort of adolescents from the Study of Cardiovascular Risks in Adolescents-ERICA-in the cities of Rio de Janeiro/RJ and Fortaleza/CE, from January 2015 to March 2019. Cases were defined as adolescents with laboratory or clinical-epidemiological diagnosis of Zika, dengue, or chikungunya, notified and registered in the Information System for Notifiable Diseases (SINAN). The cases were identified by linkage between the databases of the ERICA cohort and of SINAN. Multilevel Cox regression was employed to estimate hazard ratios (HR) as measures of association and respective 95% confidence intervals (95%CI). In comparison with adolescents living in lower socioeconomic conditions, the risk of becoming ill due to any of the three studied arboviral diseases was lower among those living in better socioeconomic conditions (HR = 0.43; 95%CI: 0.19-0.99; p = 0.047) and in the adolescents who attended school in the afternoon period (HR = 0.17; 95%CI: 0.06-0.47; p<0.001). When compared to areas whose Building Infestation Index (BII) for Aedes aegypti was considered satisfactory, a BII in the school region classified as "alert" and "risk" was associated with a higher risk of arboviral diseases (HR = 1.62, 95%CI: 0.98-2.70; p = 0.062; HR = 3.72, 95%CI: 1.27-10.9; p = 0.017, respectively). These findings indicate that living in less favored socioeconomic conditions, attending school in the morning, and having a high BII for Ae. aegypti in school's region can contribute to an increased risk of infection by Zika, dengue, or chikungunya in adolescents. The identification of residential or school areas based on those variables can contribute to the implementation of control measures in population groups and priority locations.


Food outlet visits, physical activity and body weight: variations by gender and race-ethnicity.
Recent evidence documents significant associations between community design, physical activity and obesity when adjusting for demographic covariates. Yet it is well understood that energy imbalance and weight gain are also a function of dietary patterns, and perhaps the degree of access to healthy food choices. The current study builds upon the Atlanta-based SMARTRAQ study of over 10,000 respondents and reports an integrated assessment of obesity impacts of physical activity and food outlet visitation. Respondents in the SMARTRAQ survey aged 25-65 provided BMI, self-reported physical activity levels (IPAQ), demographic factors, and where they went for food over a 2 day period. The relative effect of physical activity, neighbourhood walkability, and food outlet visitation on BMI differed significantly across gender and ethnicity. BMI in females increased with fast food and decreased with grocery store visitation and physical activity, but not with walkability or walking. BMI in males was not related to where they went for food but decreased with walking and overall physical activity and with walkability. Fast food visitation was associated with increased BMI in white respondents and grocery store visitation with decreased BMI in black respondents. Meeting moderate activity guidelines was associated with lower BMI in both black and white respondents, yet walking was only significant in predicting reduced BMI in white respondents. Obesity influences of physical activity, walkability, and where people go for food differ significantly across gender and ethnicity and offer important policy implications and insights for future research.


Visual and rapid identification of Chlamydia trachomatis and Neisseria gonorrhoeae using multiplex loop-mediated isothermal amplification and a gold nanoparticle-based lateral flow biosensor.
Sexually transmitted chlamydia and gonorrhea infections caused by the bacteria Chlamydia trachomatis and Neisseria gonorrhoeae remain a major public health concern worldwide, particularly in less developed nations. It is crucial to use a point of care (POC) diagnostic method that is quick, specific, sensitive, and user-friendly to treat and control these infections effectively. Here, a novel molecular diagnostic assay, combining multiplex loop-mediated isothermal amplification (mLAMP) with a visual gold nanoparticles-based lateral flow biosensor (AuNPs-LFB) was devised and used for highly specific, sensitive, rapid, visual, and easy identification of C. trachomatis and N. gonorrhoeae. Two unique independent primer pairs were successful designed against the ompA and orf1 genes of C. trachomatis and N. gonorrhoeae, respectively. The optimal mLAMP-AuNPs-LFB reaction conditions were determined to be 67°C for 35 min. The detection procedure, involving crude genomic DNA extraction (~5 min), LAMP amplification (35 min), and visual results interpretation (<2 min), can be completed within 45 min. Our assay has a detection limit of 50 copies per test, and we did not observe any cross-reactivity with any other bacteria in our testing. Hence, our mLAMP-AuNPs-LFB assay can potentially be used for POC testing to detect C. trachomatis and N. gonorrhoeae in clinical settings, particularly in underdeveloped regions.


Proteomic analysis of the effect of the polyphenol pentagalloyl glucose on proteins involved in neurodegenerative diseases in activated BV‑2 microglial cells.
Neuroinflammation and microglial activation are two important hallmarks of neurodegenerative diseases. Continuous microglial activation may cause the release of several cytotoxic molecules, including many cytokines that are involved in the inflammatory process. Therefore, attenuating inflammation caused by activated microglia may be an approach for the therapeutic management of neurodegenerative diseases. In addition, many studies have reported that polyphenol pentagalloyl glucose (1,2,3,4,6‑penta‑O‑galloyl‑β‑D‑glucose; PGG) is a molecule with potent anti‑inflammatory effects, such as inhibiting the release of proinflammatory cytokines. Our previous studies revealed that PGG attenuated the expression of two inflammatory cytokines (murine monocyte chemoattractant protein‑5 and pro‑metalloproteinase‑9) in lipopolysaccharide/interferon γ‑activated BV‑2 microglial cells. Additionally, PGG modulated the NF‑κB and MAPK signaling pathways by altering genes and proteins, which may affect the MAPK cascade and NF‑κB activation. The aim of the present study was to investigate the ability of PGG to modulate the expression of proteins released in activated BV‑2 microglial cells, which may be involved in the pathological process of inflammation and neurodegeneration. Proteomic analysis of activated BV‑2 cells identified 17 proteins whose expression levels were significantly downregulated by PGG, including septin‑7, ataxin‑2, and adenylosuccinate synthetase isozyme 2 (ADSS). These proteins were previously described as being highly expressed in neurodegenerative diseases and/or involved in the signaling pathways associated with the formation and growth of neuronal connections and the control of Alzheimer's disease pathogenesis. The inhibitory effect of PGG on ataxin‑2, septin‑7 and ADSS was further confirmed at the protein and transcriptional levels. Therefore, the obtained results suggest that PGG, with its potent inhibitory effects on ataxin‑2, septin‑7 and ADSS, may have potential use in the therapeutic management of neurodegenerative diseases.


Syntactic and Semantic Analysis for Extended Feedback on Computer Graphics Assignments.
Modern computer graphics courses require students to complete assignments involving computer programming. The evaluation of student programs, either by the student (self-assessment) or by the instructors (grading) can take a considerable amount of time and does not scale well with large groups. Interactive judges giving a pass/fail verdict do constitute a scalable solution, but they only provide feedback on output correctness. In this article, we present a tool to provide extensive feedback on student submissions. The feedback is based both on checking the output against test sets, as well as on syntactic and semantic analysis of the code. These analyses are performed through a set of code features and instructor-defined rubrics. The tool is built with Python and supports shader programs written in GLSL. Our experiments demonstrate that the tool provides extensive feedback that can be useful to support self-assessment, facilitate grading, and identify frequent programming mistakes.


Ecological assessment of Santa Giusta Lagoon (Sardinia, Italy).
The general environmental conditions of Santa Giusta Lagoon, an important Sardinian coastal lagoon often affected by dystrophic crises, are examined. The study considers both the monitoring data collected over the past ten years on the relevant water quality parameters and the preliminary results on the structure and heavy metal content of the surface sediments of the lagoon. These data emphasised its elevated trophic level, due to the excessive presence of plant nutrients in water, and a relative low level of heavy metal contamination. At the moment, the eutrophy--brought about the urban and industrial wastes from Oristano and Santa Giusta--can be considered the main environmental issue of the lagoon.


Dynamics of transition from static to kinetic friction.
We propose a model for a description of dynamics of cracklike processes that occur at the interface between two blocks prior to the onset of frictional motion. We find that the onset of sliding is preceded by well-defined detachment fronts initiated at the slider trailing edge and extended across the slider over limited lengths smaller than the overall length of the slider. Three different types of detachment fronts may play a role in the onset of sliding: (i) Rayleigh (surface sound) fronts, (ii) slow detachment fronts, and (iii) fast fronts. The important consequence of the precursor dynamics is that before the transition to overall sliding occurs, the initially uniform, unstressed slider is already transformed into a highly nonuniform, stressed state. Our model allows us to explain experimental observations and predicts the effect of material properties on the dynamics of the transition to sliding.


[Characteristics of cases hospitalized for severe pandemic (H1N1) 2009 in Catalonia].
Influenza pandemics may cause more severe cases. The objective was to determine the characteristics of hospitalized severe cases of pandemic influenza in Catalonia and to study risk factors for admission to intensive care unit (ICU). A prospective epidemiologic study of new cases of pandemic influenza hospitalized by their severity between June 2009 and May 2010. Hospitals were asked to declare laboratory confirmed pandemic influenza cases that met the case specific case definition for severe case. A standardized epidemiological survey was conducted to collect information on demographics, clinical characteristics, risk factors, treatment and outcome. Differences between the cases in ICU compared to other severe cases were studied with the odds ratio (OR), which were adjusted using a logistic regression model. We detected total of 773 pandemic influenza (H1N1) 2009 severe cases; 465 (60.2%) of them had at least one risk factor and the most prevalent were: pregnancy 19 (13%), asthma 87 (12%), chronic obstructive pulmonary disease 87 (11.4%) and heart disease 80 (10.5%). Required admission to ICU 293 patients (37.9%). Factors associated with ICU admission were obesity BMI>40 (adjusted OR = 2.5, 95% CI 1.4-4.5) and chronic liver disease (adjusted OR = 2.3, 95% CI 1.1-4.8). This study confirms the high prevalence of pregnancy, chronic respiratory diseases, diabetes and obesity among pandemic influenza severe cases. Obesity acts as a risk factor for ICU admission and should therefore be considered as an indicator for influenza vaccination.


The relative effectiveness of extinction and counter-conditioning in diminishing children's fear.
Two behavioural strategies for reducing learned fear are extinction and counter-conditioning, and in this study we compared the relative effectiveness of the two procedures at diminishing fear in children. Seventy-three children aged 7-12 years old (M = 9.30, SD = 1.62) were exposed to pictures of two novel animals on a computer screen during the fear acquisition phase. One of these animals was paired with a picture of a scared human face (CS+) while the other was not (CS-). The children were then randomly assigned to one of three conditions: counter-conditioning (animal paired with a happy face), extinction (animal without scared face), or control (no fear reduction procedure). Changes in fear beliefs and behavioural avoidance of the animal were measured. Counter-conditioning was more effective at reducing fear to the CS + than extinction. The findings are discussed in terms of implications for behavioural treatments of childhood anxiety disorders.


Men Experience Higher Risk of Pneumonia and Death After Intracerebral Hemorrhage.
Infectious complications worsen outcome after intracerebral hemorrhage (ICH). We investigated the impact of sex on post-ICH infections and mortality. Consecutive ICH patients (admitted to a single hospital between 1994 and 2015) were retrospectively assessed via chart review to ascertain the following in-hospital infections: urinary tract infection (UTI), pneumonia, and sepsis. Adjusted logistic regression was performed to identify associations between sex, infection, and mortality at 90 days. Two thousand and four patients were investigated, 1071 (53.7%) males. Men were more likely to develop pneumonia (21.9 vs 15.5% p < 0.001) and sepsis (3.4 vs 1.6%, p = 0.009), whereas women had higher risk of UTI (19.9 vs 11.7% p < 0.001). Multivariate analyses confirmed association between male sex and pneumonia (Odds Ratio (OR) 1.37, 95% confidence interval (CI) 1.08-1.74, p = 0.011). Male sex (OR 1.40; CI 1.07-1.85; p = 0.015) and infection (OR 1.56; CI 1.11-1.85; p = 0.011) were independently associated with higher 90-day mortality. Types and rates of infection following ICH differ by sex. Male sex independently increases pneumonia risk, which subsequently increases 90-day mortality. Sex-specific preventive strategies to reduce the risk of these complications may be one strategy to improve ICH outcomes.


Analysis of deformation of flexible hemispherical lens arrays based on soft elastomers.
In this paper, flexible hemispherical lens arrays based on soft elastomers were fabricated. Then, the effects of various geometric parameters on the deformation (i.e., hemispherical deformation and radial extension) of these lens arrays were investigated experimentally and were verified by finite element analysis. We focused on determining the relationship between the geometric parameters and the radius of curvature of the lens. We found that the height of the lens support post plays an important role in minimizing changes in the radius of curvature of the lens. The results of this research offer valuable design principles for flexible lens arrays, which can be used as an optical component of various flexible optoelectronic devices.