Targeting Autophagy Facilitates T Lymphocyte Migration by Inducing the Expression of CXCL10 in Gastric Cancer Cell Lines.
Autophagy is a type of cellular catabolic degradation process that occurs in response to nutrient starvation or metabolic stress, and is a valuable resource for highly proliferating cancer cells. Autophagy also facilitates the resistance of cancer cells to antitumor therapies. However, the involvement of autophagy in regulating CXCL10 expression in gastric cancer (GC) cells and T lymphocyte migration remains unclear. In this study, we aimed to investigate the effect of autophagy inhibition on CXCL10 expression and T lymphocyte infiltration in GC and elucidate the underlying mechanism. Analysis of public databases revealed a positive correlation between CXCL10 expression and both prognosis of patients with GC and the expression profile of T lymphocyte markers in the GCs. Chemotaxis and spheroid infiltration assays revealed that CXCL10 induced T lymphocyte migration and infiltration into GC spheroids, an in vitro three-dimensional cell culture model. In addition, in vitro autophagy inhibition in GC cells increased CXCL10 expression under both normal and hypoxic culture conditions. Further investigation on the underlying mechanism showed that in vitro autophagy inhibition suppressed the JNK signaling pathway and further enhanced CXCL10 expression in GC cells. Collectively, our results provide novel insights for understanding the role of autophagy in regulation of intra-tumor immunity.


The COVID-19 epidemic, its mortality, and the role of non-pharmaceutical interventions.
COVID-19 has developed into a pandemic, hitting hard on our communities. As the pandemic continues to bring health and economic hardship, keeping mortality as low as possible will be the highest priority for individuals; hence governments must put in place measures to ameliorate the inevitable economic downturn. The course of an epidemic may be defined by a series of key factors. In the early stages of a new infectious disease outbreak, it is crucial to understand the transmission dynamics of the infection. The basic reproduction number (R0), which defines the mean number of secondary cases generated by one primary case when the population is largely susceptible to infection ('totally naïve'), determines the overall number of people who are likely to be infected, or, more precisely, the area under the epidemic curve. Estimation of changes in transmission over time can provide insights into the epidemiological situation and identify whether outbreak control measures are having a measurable effect. For R0 > 1, the number infected tends to increase, and for R0 < 1, transmission dies out. Non-pharmaceutical strategies to handle the epidemic are sketched and based on current knowledge, the current situation is sketched and scenarios for the near future discussed.


[Reliability theory based on quality risk network analysis for Chinese medicine injection].
A new risk analysis method based upon reliability theory was introduced in this paper for the quality risk management of Chinese medicine injection manufacturing plants. The risk events including both cause and effect ones were derived in the framework as nodes with a Bayesian network analysis approach. It thus transforms the risk analysis results from failure mode and effect analysis (FMEA) into a Bayesian network platform. With its structure and parameters determined, the network can be used to evaluate the system reliability quantitatively with probabilistic analytical appraoches. Using network analysis tools such as GeNie and AgenaRisk, we are able to find the nodes that are most critical to influence the system reliability. The importance of each node to the system can be quantitatively evaluated by calculating the effect of the node on the overall risk, and minimization plan can be determined accordingly to reduce their influences and improve the system reliability. Using the Shengmai injection manufacturing plant of SZYY Ltd as a user case, we analyzed the quality risk with both static FMEA analysis and dynamic Bayesian Network analysis. The potential risk factors for the quality of Shengmai injection manufacturing were identified with the network analysis platform. Quality assurance actions were further defined to reduce the risk and improve the product quality.


Methylprednisolone pulsing of heart transplant patients in the home.
Methylprednisolone pulsing is the first form of treatment used to reverse acute moderate rejection in heart transplant patients at the University of Michigan, Ann Arbor. Before May 1986, patients who needed administration of medications to be pulsed were admitted to the hospital. With our increasing number of transplant patients, lack of hospital beds, and efforts toward cost containment, a new system was established. From June 1986 to April 1988, 53 heart transplantations were performed in 40 adults and 13 children. Home care agency nurses received in-service training by the heart transplant clinical specialist. Insurance companies were contacted directly to obtain financial approval when it was not considered a covered benefit. Of 47 episodes of rejection, 45 were successfully treated in the home with resolution, whereas hospital admission was required in two cases of rejection episodes for successful resolution. There were marked financial savings, increased patient satisfaction, no patient infections, and minimal side effects, which included hypertension in five patients, headaches in two patients, and difficulty gaining venous access in two patients. Most problems were easily handled by telephone communication. Therefore, after a 22-month experience with administration of methylprednisolone pulses in the home, we believe that this is a satisfactory method of treating patients. It is cost-effective, has minimal side effects, and leads to increased patient satisfaction.


Retinal vascular and structural changes are associated with amyloid burden in the elderly: ophthalmic biomarkers of preclinical Alzheimer's disease.
Retinal imaging may serve as an alternative approach to monitor brain pathology in Alzheimer's disease (AD). In this study, we investigated the association between retinal vascular and structural changes and cerebral amyloid-β (Aβ) plaque load in an elderly cohort. We studied a total of 101 participants, including 73 elderly subjects (79 ± 5 years, 22 male) with no clinical diagnosis of AD but reporting some subjective memory change and an additional 28 subjects (70 ± 9 years, 16 male) with clinically established AD. Following a complete dilated ocular examination, the amplitude of retinal vascular pulsations and dynamic response, retinal nerve fibre layer thickness and retinal ganglion cell layer (RGCL) thickness were determined in all patients. Systemic blood pressure and carotid-to-femoral pulse wave velocity were measured. The elderly cohort also underwent magnetic resonance imaging and 18F-florbetaben (FBB)-positron emission tomographic amyloid imaging to measure neocortical Aβ standardised uptake value ratio (SUVR), and this was used to characterise a 'preclinical' group (SUVR >1.4). The mean FBB neocortical SUVR was 1.35 ± 0.3. The amplitude of retinal venous pulsations correlated negatively with the neocortical Aβ scores (p < 0.001), whereas the amplitude of retinal arterial pulsations correlated positively with neocortical Aβ scores (p < 0.01). RGCL thickness was significantly lower in the clinical AD group (p < 0.05). The correlation between retinal vascular changes and Aβ plaque load supports the possibility of a vascular component to AD. Dynamic retinal vascular parameters may provide an additional inexpensive tool to aid in the preclinical assessment of AD.


Aphidicolin-sensitive specific common fragile sites: a biomarker of exposure to pesticides.
In this work, we analyzed the aphidicolin-sensitive common fragile sites in seven females and four males occupationally exposed to pesticides and in ten controls. The same males had been monitored one year earlier in a previous study by the same authors. Results showed enhanced expression in exposed subjects at eight bands, namely, 6q25, 7p22, 7q22, 7q32, 13q14, 14q24, 16q22, and 16q23. Most of these bonds were fragile sites and breakpoints involved in chromosome rearrangements found in hematopoietic tumors. Moreover, six of these bands were already detected, with enhanced expression, in the first monitoring carried out on male subjects. These results indicated that fragile sites analysis is a reproducible cell response to human exposure to pesticides.


Combinations of fluorescently labeled pulmonary surfactant proteins SP-B and SP-C in phospholipid films.
Hydrophobic pulmonary surfactant (PS) proteins B (SP-B) and C (SP-C) modulate the surface properties of PS lipids. Epifluorescence microscopy was performed on solvent-spread monolayers of fluorescently labeled porcine SP-B (R-SP-B, labeled with Texas Red) and SP-C (F-SP-C, labeled with fluorescein) in dipalmitoylphosphatidylcholine (DPPC) (at protein concentrations of 10 and 20 wt%, and 10 wt% of both) under conditions of cyclic compression and expansion. Matrix-assisted laser desorption/ionization (MALDI) spectroscopy of R-SP-B and F-SP-C indicated that the proteins were intact and labeled with the appropriate fluorescent probe. The monolayers were compressed and expanded for four cycles at an initial rate of 0.64 A2 x mol(-1) x s(-1) (333 mm2 x s x [-1]) up to a surface pressure pi approximately 65 mN/m, and pi-area per residue (pi-A) isotherms at 22 +/- 1 degrees C were obtained. The monolayers were microscopically observed for the fluorescence emission of the individual proteins present in the film lipid matrix, and their visual features were video recorded for image analysis. The pi-A isotherms of the DPPC/protein monolayers showed characteristic "squeeze out" effects at pi approximately 43 mN/m for R-SP-B and 55 mN/m for F-SP-C, as had previously been observed for monolayers of the native proteins in DPPC. Both proteins associated with the expanded (fluid) phase of DPPC monolayers remained in or associated with the monolayers at high pi (approximately 65 mN/m) and redispersed in the monolayer upon its reexpansion. At comparable pi and area/molecule of the lipid, the proteins reduced the amounts of condensed (gel-like) phase of DPPC monolayers, with F-SP-C having a greater effect on a weight basis than did R-SP-B. In any one of the lipid/protein monolayers the amounts of the DPPC in condensed phase were the same at equivalent pi during compression and expansion and from cycle to cycle. This indicated that only minor loss of components from these systems occurred between compression-expansion cycles. This study indicates that hydrophobic PS proteins associate with the fluid phase of DPPC in films, some proteins remain at high surface pressures in the films, and such lipid-protein films can still attain high pi during compression.


Integration of cortical thickness data in a statistical shape model of the scapula.
Knowledge about bone morphology and bone quality of the scapula throughout the population is fundamental in the design of shoulder implants. In particular, regions with the best bone stock (cortical bone) are taken into account when planning the supporting screws, aiming for an optimal fixation. As an alternative to manual measurements, statistical shape models (SSMs) have been commonly used to describe shape variability within a population. However, explicitly including cortical thickness information in an SSM of the scapula still remains a challenge. Therefore, the goal of this study is to combine scapular bone shape and cortex morphology in an SSM. First, a method to estimate cortical thickness, based on HU (Hounsfield Unit) profile analysis, was developed and validated. Then, based on the manual segmentations of 32 healthy scapulae, a statistical shape model including cortical information was created and evaluated. Generalization, specificity and compactness were calculated in order to assess the quality of the SSM. The average cortical thickness of the SSM was 2.0 ± 0.63 mm. Generalization, specificity and compactness performances confirmed that the combined SSM was able to capture the bone quality changes in the population. In this work we integrated information on the cortical thickness in an SSM for the scapula. From the results we conclude that this methodology is a valuable tool for automatically generating a large population of scapulae and deducing statistics on the cortex. Hence, this SSM can be useful to automate implant design and screw placement in shoulder arthroplasty.


Investigating the role of articulatory organs and perceptual assimilation of native and non-native fricative place contrasts.
The perceptual assimilation model (PAM; Best, C. T. [1995]. A direct realist view of cross-language speech perception. In W. Strange (Ed.), Speech perception and linguistic experience: Issues in cross-language research (pp. 171-204). Baltimore, MD: York Press.) accounts for developmental patterns of speech contrast discrimination by proposing that infants shift from untuned phonetic perception at 6 months to natively tuned perceptual assimilation at 11-12 months, but the model does not predict initial discrimination differences among contrasts. To address that issue, we evaluated the Articulatory Organ Hypothesis, which posits that consonants produced using different articulatory organs are initially easier to discriminate than those produced with the same articulatory organ. We tested English-learning 6- and 11-month-olds' discrimination of voiceless fricative place contrasts from Nuu-Chah-Nulth (non-native) and English (native), with one within-organ and one between-organ contrast from each language. Both native and non-native contrasts were discriminated across age, suggesting that articulatory-organ differences do not influence perception of speech contrasts by young infants. The results highlight the fact that a decline in discrimination for non-native contrasts does not always occur over age.


The IS4 family of insertion sequences: evidence for a conserved transposase motif.
The eight IS231 variants characterized so far (IS231 A-F, V and W) display similar transposases with an overall 40% identity. Comparison with all the prokaryotic transposable elements sequenced so far revealed that the IS231 transposases share two conserved regions with those of 35 other insertion sequences of wide origins. These insertion sequences, defining the IS4 family, have a common bipartite organization of their ends and are divided into two similarity groups. Interestingly, the transposase domains conserved within this family display similarities with the well known integrase domain shared by transposases of the IS3 and IS15 families, and integrases of retroelements. This domain is also found in IS30-related elements and Tn7 TnsB protein. Amino acid residues conserved throughout all these prokaryotic and eukaryotic mobile genetic elements define a major transposase/integrase motif, likely to play an important role in the transposition process.


Plausible improvements for selective targeting of dopamine receptors in therapy of Parkinson's disease.
Parkinson's disease (PD) is a neurodegenerative condition characterized by progressive and profound loss of dopaminergic neurons in the substantia nigra pars compacta leading to the formation of eosinophillic, intracytoplamic, proteinacious inclusions termed as lewy bodies. L-dopa remains as a gold standard for the treatment of PD, and is often combined with carbidopa to reduce the dose-limiting side effects. Long-term levodopa treatment is associated with the development of motor fluctuations and peak dose dyskinesias. Dopamine Replacement Therapy (DRT) with dopamine agonists (DAs) (ropinirole and pramipexole) is used to manage complications of L-dopa treatment, however, has been associated with numerous pharmacovigilence reports. The present review attempts to narrate the multiple receptor interaction of DAs followed by the assessment of their side effects during the treatment of PD and possible remedial strategy for selective targeting of dopamine receptors to overcome these affects in therapy of Parkinson's disease.


[Cardiac massage: the evolution of techniques].
Up to the 19th century, reanimation of persons apparently dead just included respiratory managing. Cardiac reanimation was born with the accession to anesthesia and their severe cardiac complications. Although closed-chest cardiac massage had been described from the outset of our century, bloody techniques of direct cardiac massage was especially used until the end of the fifties. Methodically, Kouvenhoven has demonstrated closed-chest cardiac massage effectiveness, and has known to lay down this technique in cardiac reanimation.


Critical region for amyloid fibril formation of mouse prion protein: unusual amyloidogenic properties of the helix 2 peptide.
To gain insight into the structural mechanism of the conformational conversion process of prion, we examined the potential amyloidogenic property of each secondary structural element in a mouse prion protein (mPrP) and discriminated their relative significance for the formation of amyloid fibrils. Although peptides corresponding to alpha-helix 2 and alpha-helix 3 (named H2 peptide and H3 peptide, respectively) formed the amyloid-like fibrils, their structures were quite different. H2 fibrils formed the ordered beta-sheet with the beta-turn conformation, and the resultant fibrils were long and straight. In contrast, H3 fibrils consisted of the beta-sheet with the random conformation, and the resultant fibrils were short and flexible. These properties are basically consistent with their hydrophobicity and beta-strand propensity profiles. To examine the cross reactivity between peptide fragments and full-length mPrP, we then carried out seeding experiments. While H2 seeds induced the formation of fibrils of full-length mPrP as quickly as full-length mPrP seeds, H3 seeds exhibited a long lag time. This implies that the region of alpha-helix 2 rather than alpha-helix 3 in mPrP has great potential for initiating fibril formation. As a whole, the alpha-helix 2 region would be crucial for the nucleation-dependent replication process of the prion protein.


Evaluation of multiplex nested polymerase chain reaction for routine hepatitis C virus genotyping in egyptian patients.
At least six HCV (hepatitis C virus) genotypes are unequally distributed worldwide. HCV genotyping guides the selection of treatment regimens and provides important epidemiological markers that enable the outbreak source to be traced and the spread of disease to be controlled. In Egypt, there is an increasing need for cost-effective, fast, and easily performable HCV genotyping assays.Recently, a multiplex PCR assay was developed to determine HCV genotypes. It employs genotype-specific primers, based on sequences of the entire core region and part of the 5'UTR of the genome. In this study, we compared a simple, new, modified multiplex PCR system for HCV genotyping with a commercially available line probe assay (INNO-LiPA) that is based on reverse hybridization. Serum samples from chronic HCV Egyptian patients (n = 73) were genotyped using the modified multiplex PCR assay, and genotypes were verified using the INNO-LiPA HCV II assay. The modified multiplex PCR method was able to type HCV-4 in 65 of 70 typeable samples (92.86%) and had 100% concordance with the INNO-LiPA assay. Genotype 4 was the most prevalent genotype in our study. Based on our results, the modified multiplex nested PCR assay is a sensitive and inexpensive alternative for HCV genotyping and can be used in routine diagnostic laboratories. INNO-LiPA may be useful as a second-line assay for genotyping samples that are indeterminate by multiplex PCR. This approach will effect better treatment optimization and a reduction of the spread of HCV.


Immunocytochemical localization of beta-glucuronidase in the male rat preputial gland.
Present knowledge of the in situ intracellular localization of acid hydrolases is mainly based on enzyme-cytochemical observations. In the preputial gland cells beta-glucuronidase and acid phosphatase were thus demonstrated in lysosome-like secretory granules and the GERL system. We applied immunocytochemistry to localize beta-glucuronidase at the earliest sites of biosynthesis. Lysosomal beta-glucuronidase was purified from preputial gland by column chromatography and SDS gel electrophoresis. Antibodies were raised in rabbit and affinity-purified preparations were used for immunocytochemistry on thin frozen sections of perfusion fixed preputial glands. Indirect procedures were applied with a second antibody labelled with rhodamine for fluorescence, and 5 or 8 nm protein A-gold probes for electron microscopy. beta-Glucuronidase occurred in all cells, except for the precursor cells, and was localized throughout the endoplasmic reticulum and perinuclear space, in all Golgi cisternae and storage granules, and in autophagic vacuoles. Thus in the preputial gland cell, beta-glucuronidase is present in both the lysosomal and the secretory system.


Intracellular sodium modulates the state of protein kinase C phosphorylation of rat proximal tubule Na+,K+-ATPase.
The natriuretic hormone dopamine and the antinatriuretic hormone noradrenaline, acting on alpha-adrenergic receptors, have been shown to bidirectionally modulate the activity of renal tubular Na+,K+-adenosine triphosphate (ATPase). Here we have examined whether intracellular sodium concentration influences the effects of these bidirectional forces on the state of phosphorylation of Na+,K+-ATPase. Proximal tubules dissected from rat kidney were incubated with dopamine or the alpha-adrenergic agonist, oxymetazoline, and transiently permeabilized in a medium where sodium concentration ranged between 5 and 70 mM. The variations of sodium concentration in the medium had a proportional effect on intracellular sodium. Dopamine and protein kinase C (PKC) phosphorylate the catalytic subunit of rat Na+,K+-ATPase on the Ser23 residue. The level of PKC induced Na+,K+-ATPase phosphorylation was determined using an antibody that only recognizes Na+,K+-ATPase, which is not phosphorylated on its PKC site. Under basal conditions Na+,K+-ATPase was predominantly in its phosphorylated state. When intracellular sodium was increased, Na+,K+-ATPase was predominantly in its dephosphorylated state. Phosphorylation of Na+,K+-ATPase by dopamine was most pronounced when intracellular sodium was high, and dephosphorylation by oxymetazoline was most pronounced when intracellular sodium was low. The oxymetazoline effect was mimicked by the calcium ionophore A23187. An inhibitor of the calcium-dependent protein phosphatase, calcineurin, increased the state of Na+,K+-ATPase phosphorylation. The results imply that phosphorylation of renal Na+,K+-ATPase activity is modulated by the level of intracellular sodium and that this effect involves PKC and calcium signalling pathways. The findings may have implication for the regulation of salt excretion and sodium homeostasis.


Probiotic supplementation reduces the risk of bacterial translocation in experimental short bowel syndrome.
Probiotics are live organisms that survive passage through the gastrointestinal tract and have beneficial effects on the host. Lactobacillus and Bifidobacterium have been recommended for cholesterol lowering, acute diarrhea, prevention of cancer, or inflammatory bowel disease. On the other hand, after massive bowel resection, bacterial overgrowth is frequent and favors bacterial translocation (BT). The possible beneficial effects of Bifidobacterium lactis (BL) administration on BT in experimental short bowel syndrome (SBS), have not been investigated. The aim of this study was to test the hypothesis that BL administration decreases BT in SBS in animals fed orally. One hundred twenty-eight adult Wistar rats fed orally with standard rat chow and tap water "ad libitum" were maintained in individual metabolic cages for 10 days and divided into 3 groups: control group (n = 71): nonmanipulated animals; RES group (n = 39): 80% gut resection from 10 cm beyond the angle of Treitz to 10 cm above the cecum; RES-PRO group (n = 18): same resection and daily 7.8 x 10(8) CFU B Lactis administration, after orogastric intubation. At the end of the experiment they were killed, and mesenteric lymph nodes (MLN) and peripheral and portal blood specimens were recovered and cultured. Bacterial identification in blood was made by conventional methods, and MLN culture was considered positive with a growth over 100 CFU/g. Bacterial translocation was detected in 6% of control group rats. The incidence of BT in the RES group was 87% (34 of 39), whereas only 50% (9 of 18) of RES-PRO animals had BT (P <.05). The relative risk reduction (RRR) was 0.43 (95% Cl 0.14 to 0.72), and the number needed to treat (NNT) was 3 (95% Cl 2 to 8). In other words, animals that received BL had the risk of BT reduced by 43% (RRR of 0.43), and of every 3 animals treated, 1 is expected to be free of BT (NNT of 3). Administration of B Lactis reduces the incidence of BT in adult Wistar rats after 80% gut resection.


On medications for burns in classical antiquity.
Egyptian, Greek, Roman, and early Byzantine medical pharmaceutical works show a fairly sophisticated array of simple and compound remedies for burns and scalds. Chief among ancient writings that provide specific botany, minerals, and similar substances used in burn treatment are several Egyptian papyri, the Hippocratic On Wounds, and writings by Celsus, Dioscorides, Pliny the Elder, and Paul of Aegina. Over 70 plants and minerals are identified according to modern nomenclatures. The ancients sought especially those ingredients that would promote rapid healing with a minimum of scarring.


Maxillofacial Changes in Melnick-Needles Syndrome.
Background. Melnick-Needles Syndrome is rare congenital hereditary skeletal dysplasia caused by mutations in the FLNA gene, which codifies the protein filamin A. This condition leads to serious skeletal abnormalities, including the stomatognathic region. Case Presentation. This paper describes the case of a 13-year-old girl diagnosed with Melnick-Needles Syndrome presenting with different forms of skeletal dysplasia, such as cranial hyperostosis, short upper limbs, bowed long bones, metaphyseal thickening, genu valgum (knock-knee), shortened distal phalanges, narrow pelvis and shoulders, rib tapering and irregularities, elongation of the vertebrae, kyphoscoliosis, micrognathia, hypoplastic coronoid processes of the mandible, left stylohyoid ligament suggesting ossification, and dental development anomalies. Conclusion. Knowledge of this rare syndrome on the part of dentists is important due to the fact that this condition involves severe abnormalities of the stomatognathic system that cause an impact on the development of the entire face as well as functional and esthetic impairments.


HIV risk-related behaviors in the United States household population aged 15-44 years: data from the National Survey of Family Growth, 2002 and 2006-2010.
This report presents national estimates of selected HIV risk-related behaviors among men and women 15-44 years of age in the United States, based on the 2006-2010 National Survey of Family Growth (NSFG). Data from the 2006-2010 NSFG are compared with data from the 2002 NSFG. Data for 2006-2010 were collected through in-person interviews with a national sample of 22,682 men and women aged 15-44 years in the household population of the United States. The measures presented in this report were collected using audio computer-assisted self-interviewing (ACASI), in which the respondent enters his or her own answers into the computer without telling them to an interviewer. The response rate for the 2006-2010 NSFG was 77%, 78% for women and 75% for men. HIV risk-related behavioral measures examined in this report include sexual risk, drug risk, and recent STD treatment. Approximately 10% of men and 8% of women in 2006-2010 reported at least one of the HIV risk-related behavioral measures examined in this report, representing 6.5 million men and 4.9 million women in the general U.S. household population. This represents a decline from the 13% of men and 11% of women who reported one or more of these measures in 2002. This decline appears to be due to a decrease in sexual risk behaviors reported in 2006-2010, however further analysis as well as comparisons with other household surveys are needed to fully understand and describe trends over time. Significant variations were seen by demographic and socioeconomic characteristics including age, race and Hispanic origin, sex, education, and poverty level income. Among men, those with recent prison experience were more likely than other men to report one or more HIV risk-related behaviors in the past year.


Generalized Knudsen Number for Unsteady Fluid Flow.
We explore the scaling behavior of an unsteady flow that is generated by an oscillating body of finite size in a gas. If the gas is gradually rarefied, the Navier-Stokes equations begin to fail and a kinetic description of the flow becomes more appropriate. The failure of the Navier-Stokes equations can be thought to take place via two different physical mechanisms: either the continuum hypothesis breaks down as a result of a finite size effect or local equilibrium is violated due to the high rate of strain. By independently tuning the relevant linear dimension and the frequency of the oscillating body, we can experimentally observe these two different physical mechanisms. All the experimental data, however, can be collapsed using a single dimensionless scaling parameter that combines the relevant linear dimension and the frequency of the body. This proposed Knudsen number for an unsteady flow is rooted in a fundamental symmetry principle, namely, Galilean invariance.


Variable-addressability electronic binocular system.
The eye's acuity varies across its field of view (FOV), decreasing to 10% of its axial value at only 20 degrees. We describe an optical system that radially remaps the pixels of a miniature display or sensor to match the varying acuity of the eye across its FOV. The variable-acuity technique increases the FOV of an electronic binocular system without any apparent loss in image quality. The result is a better, more efficient human-machine interface.


Cost-effectiveness of activated protein C in real-life clinical practice.
Recombinant human activated protein C (rhAPC) has been reported to be cost-effective in severely ill septic patients in studies using data from a pivotal randomized trial. We evaluated the cost-effectiveness of rhAPC in patients with severe sepsis and multiple organ failure in real-life intensive care practice. We conducted a prospective observational study involving adult patients recruited before and after licensure of rhAPC in France. Inclusion criteria were applied according to the label approved in Europe. The expected recruitment bias was controlled by building a sample of patients matched for propensity score. Complete hospitalization costs were quantified using a regression equation involving intensive care units variables. rhAPC acquisition costs were added, assuming that all costs associated with rhAPC were already included in the equation. Cost comparisons were conducted using the nonparametric bootstrap method. Cost-effectiveness quadrants and acceptability curves were used to assess uncertainty of the cost-effectiveness ratio. In the initial cohort (n = 1096), post-license patients were younger, had less co-morbid conditions and had failure of more organs than did pre-license patients (for all: P < 0.0001). In the matched sample (n = 840) the mean age was 62.4 +/- 14.9 years, Simplified Acute Physiology Score II was 56.7 +/- 18.5, and the number of organ failures was 3.20 +/- 0.83. When rhAPC was used, 28-day mortality tended to be reduced (34.1% post-license versus 37.4% pre-license, P = 0.34), bleeding events were more frequent (21.7% versus 13.6%, P = 0.002) and hospital costs were higher (47,870 euros versus 36,717 euros, P < 0.05). The incremental cost-effectiveness ratios gained were as follows: 20,278 euros per life-year gained and 33,797 euros per quality-adjusted life-year gained. There was a 74.5% probability that rhAPC would be cost-effective if there were willingness to pay 50,000 euros per life-year gained. The probability was 64.3% if there were willingness to pay 50,000 euros per quality-adjusted life-year gained. This study, conducted in matched patient populations, demonstrated that in real-life clinical practice the probability that rhAPC will be cost-effective if one is willing to pay 50,000 euros per life-year gained is 74.5%.


Immunolocalization of estrogen receptor alpha and beta in human fetal prostate.
We examined the immunolocalization of estrogen receptor (ER)alpha and ERbeta in the human fetal prostate. Tissue sections from human fetal prostates at 7 to 22 weeks of gestation were stained with antibodies to ERalpha, ERbeta, and cytokeratin 10 and 14. ERalpha expression was not detected until 15 weeks of gestation with sparse staining in the utricle. By 19 weeks increased ERalpha expression was seen in the luminal cells of the ventral urogenital epithelium (UGE), basal cells of the dorsal UGE, utricle, distal periurethral ducts, peripheral stroma and posterior prostatic duct. K14 was detected in basal cells of the UGE and in several posterior acini. At 22 weeks ERalpha expression was more intense in all of these areas. ERbeta was expressed throughout the UGE, ejaculatory ducts, müllerian ducts and entire stroma at 7 weeks. Intense ERbeta staining was observed in these areas and in the prostatic buds by 8 weeks with persistent intense staining through 22 weeks. To our knowledge we report the first immunolocalization of ERalpha in the human fetal prostate and the earliest demonstration of ERbeta expression in the prostate at 7 weeks of gestation. ERbeta expression is intense during ductal morphogenesis, suggesting a role in normal glandular growth and proliferation. The induction of squamous metaplasia in the UGE, distal periurethral ducts and utricle is associated with ERalpha expression in these areas, while the induction of squamous metaplasia in peripheral prostatic acini is associated with peripheral stromal ERalpha expression. This study suggests estrogen signaling pathways in the human fetal prostate via ERalpha that involve epithelial-epithelial and epithelial-stromal interactions.


Phosphorylated HSP27 associates with the activation-dependent cytoskeleton in human platelets.
The three prominently phosphorylated 29-kD proteins in thrombin-activated human platelets are forms of the mammalian 27-kD heat-shock protein (HSP27). Though the function of HSP27 is not yet known, its phosphorylation is highly correlated with platelet secretion, and recent evidence in nonhematopoietic cells suggests that HSP27 regulates cortical actin filament assembly. Therefore, the subcellular location and phosphorylation state of HSP27 in resting and thrombin-activated platelets was studied. Platelets were fractionated by established Triton X-100 lysis methods followed by differential centrifugation to obtain the 14,000g fraction (low-speed cytoskeleton), 100,000g fraction (membrane skeleton), and the 100,000g supernatant fraction containing soluble cytosolic proteins. In resting platelets, HSP27 was present principally in the 100,000g supernatant fraction. Platelet activation with thrombin led to translocation of the majority of HSP27 to the low-speed cytoskeleton. This association was reversible by DNase, supporting the idea that HSP27 is a specific component of the actin cytoskeleton. Immunofluorescence studies similarly showed HSP27 is cytoplasmic in resting platelets but colocalizes with actin in fully spread, glass-activated platelets. Immunoprecipitation studies showed a small amount of constitutively phosphorylated HSP27 in resting platelets, but phosphorylation of the majority of HSP27 after thrombin activation. After activation, virtually all phosphorylated HSP27 was found in the low-speed cytoskeletal fraction, and each of the three phosphorylated forms of HSP27 were present by two-dimensional autoradiography. Furthermore, in time-course studies, the phosphorylation of HSP27 occurred just before localization of HSP27 to the low-speed pellet. These results show that, after platelet activation, HSP27 is first phosphorylated and then translocated from the cytoplasm to the assembling cytoskeleton, and suggest that HSP27 phosphorylation may be important to the binding of HSP27 to cytoskeletal components and the cytoskeletal rearrangements characteristic of platelet activation.


[Design of Intravascular Ultrasound-enhanced Thrombolysis Excitation System Based on FPGA].
An intravascular ultrasound-enhanced thrombolysis excitation system with adjustable frequency, amplitude and duty cycle was designed based on FPGA (ZYNQ-7Z020). Firstly, the FPGA generated waveform amplitude binary data based on direct digital frequency synthesis (DDS) technology, and then the data was converted into burst signal through an external daughter card, which included D/A conversion circuit, active low-pass filter, power amplifier circuit and impedance matching circuit. The test results demonstrated that the output waveform reached the target with advantages of simple implementation and flexible control, the peak negative pressure generated from ultrasound transducer was doubled by means of an electrical impedance matching network. In vitro thrombus models were applied to verify the excitation system, it turned out that ultrasound cavitation effect generated could accelerate the penetration of urokinase and increase the thrombolysis rate by about 20%.


Orchidectomy increases expression and activity of Cu/Zn-superoxide dismutase, while decreasing endothelial nitric oxide bioavailability.
This study examines the effect of male sex hormones on the release, metabolism and function of endothelial nitric oxide (eNO) in rat aorta. Aortic segments from orchidectomized and control male Sprague-Dawley rats were used to measure eNO synthase (eNOS) expression, nitric oxide (NO) release, acetylcholine (ACh)- and sodium nitroprusside (SNP)-induced relaxation and Cu/Zn-superoxide dismutase (SOD) expression and activity. eNOS expression as well as basal and ACh-induced NO release were similar in arteries from both groups of rats. Basal superoxide anion production was similar in arteries from both groups, while ACh-induced superoxide anion formation was greater in arteries from orchidectomized than control rats. Orchidectomy increased the vasodilator effect induced by ACh, but did not alter that induced by SNP. SOD, a superoxide anion scavenger, did not modify the SNP-induced relaxation in aortas from control or orchidectomized rats. The membrane-permeable mimetic of SOD, tempol, increased the SNP-induced relaxation more in aortas from orchidectomized than control rats. The effect of endogenous SOD inhibitor, diethyl-dithiocarbamate, reduced the relaxation induced by SNP in segments from both groups of rats. The expression and activity of Cu/Zn-SOD were greater in aortas from orchidectomized than control rats. These data show that endogenous male sex hormone deprivation altered neither eNOS expression nor eNO release, while it increased the expression and activity of Cu/Zn-SOD. However, the predominant vascular effect of orchidectomy is to increase NO metabolism.


Ngutulu Kagwero (agents of change): study design of a participatory comic pilot study on sexual violence prevention and post-rape clinical care with refugee youth in a humanitarian setting in Uganda.
With over 1.4 million refugees, Uganda is Sub-Saharan Africa's largest refugee-hosting nation. Bidi Bidi, Uganda's largest refugee settlement, hosts over 230,000 residents. There is a dearth of evidence-based sexual violence prevention and post-rape clinical care interventions in low- and middle-income humanitarian contexts tailored for refugee youth. Graphic medicine refers to juxtaposing images and narratives, often through using comics, to convey health promotion messaging. Comics can offer youth-friendly, low-cost, scalable approaches for sexual violence prevention and care. Yet there is limited empirical evaluation of comic interventions for sexual violence prevention and post-rape clinical care. This paper details the study design used to develop and pilot test a participatory comic intervention focused on sexual violence prevention through increasing bystander practices, reducing sexual violence stigma, and increasing post exposure prophylaxis (PEP) knowledge with youth aged 16-24 and healthcare providers in Bidi Bidi. Participants took part in a single-session peer-facilitated workshop that explored social, sexual, and psychological dimensions of sexual violence, bystander interventions, and post-rape clinical care. In the workshop, participants completed a participatory comic book based on narratives from qualitative data conducted with refugee youth sexual violence survivors. This pilot study employed a one-group pre-test/post-test design to assess feasibility outcomes and preliminary evidence of the intervention's efficacy. Challenges included community lockdowns due to COVID-19 which resulted in study implementation delays, political instability, and attrition of participants during follow-up surveys. Lessons learned included the important role of youth facilitation in youth-centred interventions and the promise of participatory comics for youth and healthcare provider engagement for developing solutions and reducing stigma regarding SGBV. The Ngutulu Kagwero (Agents of change) project produced a contextually and age-tailored comic intervention that can be implemented in future fully powered randomized controlled trials to determine effectiveness in advancing sexual violence prevention and care with youth in humanitarian contexts.


Rupture zones of great earthquakes in the alaska-aleutian arc, 1784 to 1980.
Historical documents indicate that great earthquakes ruptured at least a 500-kilometer-long segment of the plate boundary near the Alaska Peninsula in 1788 and 1847. At least half of a major seismic gap in the Shumagin Islands ruptured during those shocks but has not experienced a great earthquake for at least 77 years. Large shocks along this and other plate boundaries occur in bursts followed by several decades during which there is very little energy release.


Effectiveness of turning with unequal time intervals on the incidence of pressure ulcer lesions.
This paper reports a study investigating whether repositioning patients lying on a pressure-reducing mattress alternately for 2 hours in a lateral position and 4 hours in a supine position reduces the incidence of pressure ulcers in comparison with repositioning every 4 hours. Repositioning is commonly recognized as an effective preventive measure. Almost no research has been carried out so far on the necessary turning frequencies to prevent pressure ulcer lesions. The pressure is higher in a lateral than in a supine position. A two-arm randomized controlled trial was conducted in 16 Belgian elder care nursing homes. Patients with non-blanchable erythema were randomly assigned to either an experimental or a control group. In the experimental group (n = 122), patients were repositioned alternately 2 hours in a lateral position and 4 hours in a supine position. In the control group (n = 113), patients were repositioned every 4 hours. The sitting protocol was identical in both groups. Pressure areas were observed daily and classified according to the four grades of the European Pressure Ulcer Advisory Panel. In the experimental group, 16.4% patients developed a pressure ulcer lesion (grade 2-4), while 21.2% did so in the control group. The incidence was not statistically significantly different between the two groups (P = 0.40). The severity (P = 0.65) and location (P = 0.19) of pressure ulcer lesions, and the time to developing them (P = 0.29) were also similar in both groups. No patient developed a pressure ulcer at the hips. A considerable number of patients changed from a lateral to a supine position between the turning intervals. More frequent repositioning on a pressure-reducing mattress does not necessarily lead to fewer pressure ulcer lesions and consequently cannot be considered as a more effective preventive measure.


[Assessment of acute neurotoxic effect of exposure to certain organic solvents based on an analysis of bioelectric function of the rat cerebral cortex].
The aim of this study was to assess the effect of four organic solvents (toluene, mesitylene, pseudocumene and hemimellitine) on the central nervous system (NCS) on the basis of changes in spontaneous EEG of the cerebral cortex and hippocampus functions occurring under conditions of acute exposure. Electrophysiological experiments were performed on rats with electrodes chronically implanted in the selected brain structures. The peripheral blood solvent concentrations were determined in rats operated without using gas chromatography combined with head space technique. Electrophysiological examinations revealed statistically significant quantitative changes in the cerebral cortex and hippocampus electroencephalograms after i.p. injections of equimolar solvents. The relationship between changes in spontaneous EEG and solvent concentrations in the blood was indicated. It was found that the central nervous system is mostly affected by the solvent whose concentration in blood is lowest (hemimellitine).


Depression in patients treated with haemodialysis: a cross-sectional study.
The increasing incidence of end-stage renal disease in the Palestinian population and the effect of the disease on the psychological status of the patient underlie the importance of increasing knowledge about the mental health status of patients with end-stage renal disease. The aim of this study was to estimate the prevalence of depression in Palestinian patients treated with haemodialysis and its correlation with patients' clinical characteristics, health-related quality of life (HRQoL), and adherence to medications. In this cross-sectional study, we collected a convenience sample from ten haemodialysis centres in the West Bank, occupied Palestinian territory, over 3 months in 2015. The Beck Depression Inventory-II scale (BDI-II) was used to assess depression, the EuroQol-5 Dimension scale was used to assess HRQoL, and the Morisky Medication Adherance-8 scale was used to assess compliance. We used SPSS version 16.0 for all statistical analyses. The study was approved by the Institutional Review Board at the An-Najah National University. Informed verbal consent was obtained from the participants before the start of the study. We interviewed 286 patients who were treated with haemodialysis. The mean age was 52·0 years (SD 14·3), and 172 (60%) patients were men. The median number of years of dialysis was 2 years (IQR 1-4). 209 (73%) patients had depression. Most participants were non-compliant with their drug regimens and had low HRQoL. High depression scores were associated with old age (p<0·0001), female sex (p=0·036), low income (p=0·041), living in rural areas or in a camp (p=0·032), not doing regular exercise (p<0·0001), unemployment (p<0·0001), having multiple comorbidities (p<0·0001), and low adherence to medications (p=0·0075). We found an inverse correlation between depression and HRQoL (p<0·0001). This study is to our knowledge the first of its kind in the West Bank. The incidence of depression is higher than reported in other communities. Most patients treated with haemodialysis were moderately to severely depressed and had low HRQol. There is a need to provide for a patient's needs in term of psychologist interviews and pharmacological and non-pharmacological interventions. None.


Histamine release in the dog after leukocyte lysate injection.
Mixed leukocyte suspensions, containing 10(6) leukocytes per ml, were prepared from dog peripheral blood by dextran sedimentation. Lysates of these suspensions, prepared by sonification, were administered intravenously to the autologous dogs. The plasma histamine levels were increased to an average value 320% above the control values (P < 0.001). The individual elements in the mixed leukocyte suspensions were separated by sucrose gradient and glass bead column fractionation procedures, and purified suspensions of platelets (no other formed elements present), lymphocytes (95 to 100%), and granulocytes (90 to 98%) were obtained. Lysates of these suspensions all had significant histamine-releasing activity when administered intravenously to dogs. Although leukocytes and platelets from other species are known to harbor mediators of histamine release, this study provides the first demonstration of the histamine-releasing activity of dog leukocytes and platelets. Many of the studies of leukocyte and platelet histamine-releasing factors have employed in vitro systems leaving the in vivo role of these factors in doubt. The present studies provide evidence that leukocyte and platelet histamine-releasing factors have in vivo activity.


Bacterial communities in the sediments of Dianchi Lake, a partitioned eutrophic waterbody in China.
Bacteria play an important role in the decomposition and cycling of a variety of compounds in freshwater aquatic environments, particularly nutrient-rich eutrophic lakes. A unique Chinese eutrophic lake--Dianchi--was selected for study because it has two separate and distinct basins, Caohai with higher organic carbon levels and Waihai with lower organic carbon levels. Sediment bacterial communities were studied in the two basins using samples collected in each season from June 2010 to March 2011. Barcoded pyrosequencing based on the 16 S rRNA gene found that certain common phyla, Proteobacteria, Bacteroidetes, Firmicutes and Chloroflexi, were dominant in the sediments from both basins. However, from the class to genus level, the dominant bacterial groups found in the sediments were distinct between the two basins. Correlation analysis revealed that, among the environmental parameters examined, total organic carbon (TOC) accounted for the greatest proportion of variability in bacterial community. Interestingly, study results suggest that increasing allochthonous organic carbon could enhance bacterial diversity and biomass in the sediment. In addition, analysis of function genes (amoA and nosZ) demonstrated that ammonia-oxidizing bacteria (AOB) were dominant in sediments, with 99% belonging to Nitrosomonas. Denitrifying bacteria were comparatively diverse and were associated with some cultivatable bacteria.


[Alcohol and health: attitudes, habits and knowledge of a group of young physicians].
By means of a set of questions the Authors analyze the habits, the attitudes and the knowledge of a group of young medical doctors, concerning the problem of alcohol and health. People interviewed are 873 Medical Reserve Officer Cadets who attended the propedeutic course at the Military Medical School of Florence from September 1987 to May 1988. These people formed a considerable part of the young male medical doctors who had graduated in Italy the previous year. This set of questions is based on the multiple choice system, with 37 questions divided in 4 sections: 1. access to the set of questions with personal information and previous studies; 2. habits and attitudes of the person concerning the consumption of alcoholic drinks; 3. general knowledge of some legal and epidemiological aspects; 4. specific knowledge of the alcohol as a risk factor and of the diagnosis and the prevention of the alcohol related pathologies. The central role of the university in acquiring the knowledge of people interviewed, clearly results from the analysis of the answers. Only few young people assert they got their knowledge from scientific publications. The belief that drinking alcohol with the meals is healthy, is more evident in the South than in the North of Italy; at the same time the prevalence of alcohol related diseases seems to increase moving from Southern to Northern Italy. The more moderate attitude of parents in Northern Italy, seems to be somehow affected by the prevalence of alcohol related diseases in this area. Most young doctors do not drink either light alcoholic drinks or spirits to excess, however 9 people claim to drink wine both with the meals and between, and some 20 claim to drink spirits once a day or even more. A remarkable part of people interviewed seems not to have a full understanding of self-definitions as "abstemious", "moderate drinker", "normal drinker", "heavy drinker". These definitions often do not fit with the quantities declared. The knowledge about metabolism and immediate effects of alcohol is not always proper: it is particularly surprising that more than a third of doctors think that alcohol warms the body and helps to bear low temperature. The poor knowledge of the epidemiological aspects of alcohol consumption is not acceptable, testifying the remarkable difficulty in having a global vision and a right dimension of the problem. In particular an inadequate evaluation of the seriousness of the alcohol related pathologies, considered insufficiently represented among the death causes by one fifth, emerges from the answers.(ABSTRACT TRUNCATED AT 400 WORDS)


β-Thalassemia gene mutations in Antalya, Turkey: results from a single centre study.
β-Thalassemia (β-thal) is a common autosomal recessive disorder resulting from over 300 different mutations of the β-globin genes. Our aim was to create a mutation map of β-thal in the province of Antalya, Turkey. In this study, mutation analysis of a total 146 of β-thal patients followed at the Thalassemia Center of the Antalya Education and Research Hospital, Antalya, Turkey, were included. Direct DNA sequence analysis was performed for mutation scanning of the β-globin gene. One hundred and forty-six patients with β-thal including all types were analyzed, and 14 different β-thal mutations were detected. The most frequently seen mutation was HBB: c.93 - 21G > A [IVS-I-110 (G > A)] (52.7%), followed by HBB: .c.92 + 6T > C [IVS-I-6 (T > C)] (14.4%), HBB: c.-80T > A [-30 (T > A)] (8.2%), HBB: c.315 + 1G > A [IVS-II-1 (G > A)] (8.2%), which made up 83.1% of the observed mutations. Our results indicate the importance of micromapping and epidemiology studies of thalassemia, which will assist in establishing the national prevention and control program in Turkey.


Staphylococcus aureus Quorum Regulator SarA Targeted Compound, 2-[(Methylamino)methyl]phenol Inhibits Biofilm and Down-Regulates Virulence Genes.
Staphylococcus aureus is a widely acknowledged Gram-positive pathogen for forming biofilm and virulence gene expressions by quorum sensing (QS), a cell to cell communication process. The quorum regulator SarA of S. aureus up-regulates the expression of many virulence factors including biofilm formation to mediate pathogenesis and evasion of the host immune system in the late phases of growth. Thus, inhibiting the production or blocking SarA protein might influence the down-regulation of biofilm and virulence factors. In this context, here we have synthesized 2-[(Methylamino)methyl]phenol, which was specifically targeted toward the quorum regulator SarA through in silico approach in our previous study. The molecule has been evaluated in vitro to validate its antibiofilm activity against clinical S. aureus strains. In addition, antivirulence properties of the inhibitor were confirmed with the observation of a significant reduction in the expression of representative virulence genes like fnbA, hla and hld that are governed under S. aureus QS. Interestingly, the SarA targeted inhibitor showed negligible antimicrobial activity and markedly reduced the minimum inhibitory concentration of conventional antibiotics when used in combination making it a more attractive lead for further clinical tests.


Pharmacogenetics of clinical response to risperidone.
Despite risperidone's proven safety and efficacy, existing pharmacogenetic knowledge could be applied to improve its clinical use. The present work aims to summarize the information about genetic polymorphisms affecting risperidone adverse reactions and efficacy during routine clinical practice. The most relevant genes involved in the metabolism of the drug (i.e., CYP2D6, CYP3A and ABCB1) appear to have the greatest potential to predict differences in plasma concentrations of the drug and its interactions, but also relate to side effects, such as neuroleptic syndrome, weight gain or polydipsia. Other genes that have been found in association at least twice with any adverse reactions including metabolic changes, extrapyramidal symptoms or prolactine increase are: 5HT2A; 5HT2C; 5HT6; DRD2; DRD3; and BDNF. Some of these genes (5HTR2A, DRD2 and DRD3), along with 5-HTTLPR and COMT, have also been reported to be related with negative clinical outcomes. However, there is not yet enough evidence to support their routine screening during clinical practice.


Depression is associated with self-rated frailty in older adults from an outpatient clinic: a prospective study.
ABSTRACTObjectives:The aim of the present study was to evaluate the association between depression and SSRI monotherapy and frailty both baseline and prospectively in older adults. Prospective cohort study, 12-month follow-up. Geriatric outpatient clinic in São Paulo, Brazil. A total of 811 elderly adults aged 60 or older. Depression was diagnosed as follows: (1) a diagnosis of major depression disorder (MDD) according to DSM-5; or (2) an incomplete diagnosis of MDD, referred to as minor or subsyndromic depression, plus Geriatric Depression Scale 15-itens ≥ 6 points, and social or functional impairment secondary to depressive symptoms and observed by relatives. Frailty evaluation was performed through the FRAIL questionnaire, which is a self-rated scale. Trained investigators blinded to the baseline assessment conducted telephone calls to evaluate frailty after 12-month follow-up. The association between depression and the use of SSRI with frailty was estimated through a generalized estimating equation adjusted for age, gender, total drugs, and number of comorbidities. Depression with SSRI use was associated with frailty at baseline (OR 2.82, 95% CI = 1.69-4.69) and after 12 months (OR 2.75, 95% CI = 1.84-4.11). Additionally, depression with SSRI monotherapy was also associated with FRAIL subdomains Physical Performance (OR 1.99, 95% CI = 1.29-3.07) and Health Status (OR 4.64, 95% CI = 2.11-10.21). SSRI use, without significant depressive symptoms, was associated with subdomain Health Status (OR 1.52, 95% CI = 1.04-2.23). It appears that depression with SSRI is associated to frailty, and this association cannot be explained only by antidepressant use.


The effect of inflammation on blood vessel area in Rosenthal's canal in the cat cochlea.
The quantitative analysis of spiral ganglion cells is important. It is conventionally expressed as a cell density, the number of cells within Rosenthal's canal divided by its area. The area of Rosenthal's canal conventionally excludes the areas of blood vessels within it. If blood vessels proliferate in an inflammatory response then excluding their area may result in an under-estimate of cell loss. This study investigates whether blood vessel area increases with inflammation. Eighteen implanted and stimulated cat cochleas were studied. Using computer aided analysis techniques we measured the areas of Rosenthal's canals and its blood vessels. A histologist quantitatively graded the inflammation in each cochlea. Blood vessel area increased with the grade of inflammation. Multiple regression analysis showed this effect was significant (P < 0.01). This increase in blood vessel area may have an effect on density measurements made by excluding that area, leading to an under-estimate of ganglion cell loss.


Vasoactive Intestinal Peptide Promotes Corneal Allograft Survival.
Corneal transplantation is the most prevalent form of tissue transplantation. The success of corneal transplantation mainly relies on the integrity of corneal endothelial cells (CEnCs), which maintain graft transparency. CEnC density decreases significantly after corneal transplantation even in the absence of graft rejection. To date, different strategies have been used to enhance CEnC survival. The neuropeptide vasoactive intestinal peptide (VIP) improves CEnC integrity during donor cornea tissue storage and protects CEnCs against oxidative stress-induced apoptosis. However, little is known about the effect of exogenous administration of VIP on corneal transplant outcomes. We found that VIP significantly accelerates endothelial wound closure and suppresses interferon-γ- and tumor necrosis factor-α-induced CEnC apoptosis in vitro in a dose-dependent manner. In addition, we found that intracameral administration of VIP to mice undergoing syngeneic corneal transplantation with endothelial injury increases CEnC density and decreases graft opacity scores. Finally, using a mouse model of allogeneic corneal transplantation, we found for the first time that treatment with VIP significantly suppresses posttransplantation CEnC loss and improves corneal allograft survival.


Hepatic angiosarcoma five years following spontaneous intraperitoneal bleed of a hepatic mass.
Primary hepatic angiosarcoma is a rare and rapidly fatal disease. We present the highly unusual identification of this lesion five years after the initial clinical presentation.In 2003, a 32-year-old man presented with abdominal pain, tachycardia, and evidence of hemorrhage. A CT scan showed a hepatic mass with intralesional hemorrhage, intraperitoneal blood, and splenomegaly. The patient was stabilized clinically. Laparoscopic core biopsies demonstrated no malignancy, only findings consistent with an old hemorrhage. Contralateral lobe biopsies revealed normal liver tissue. A metastatic workup was negative and the decision was made to observe the patient clinically with radiographic follow-up, given his suspected portal hypertension based on thrombocytopenia and splenomegaly.Sequential imaging demonstrated a decrease in the size of the mass from 12.0 cm in 2003 to 3.0 cm in 2007. Subsequent newly identified esophageal varices prompted a reevaluation of the case. A repeat biopsy demonstrated a neoplasm of vascular etiology and uncertain malignant potential. By early 2008 the lesion had increased to 4.8 cm and was resected via a left hepatic lobectomy. An extremely vascular lesion with surrounding dense fibrosis was identified and pathologic examination demonstrated a high-grade angiosarcoma.We are unaware of any previous reports suggesting such a prolonged natural history of hepatic angiosarcoma. This case may represent the possibility of malignant transformation of a lower grade vascular neoplasm such as hepatic epithelioid hemangioendothelioma to an angiosarcoma.


Asymmetric Synthesis of Chiral Cyclopentanes Bearing an All-Carbon Quaternary Stereocenter by Zirconium-Catalyzed Double Carboalumination.
Herein, we report a zirconium-catalyzed enantio- and diastereoselective inter/intramolecular double carboalumination of unactivated 2-substituted 1,5-dienes, which provides efficient and direct access to chiral cyclopentanes through the generation of two stereocenters, including one all-carbon quaternary stereocenter, generally with excellent diastereo- and high enantioselectivity. This tandem carboalumination process creates two new C-C bonds as well as one C-Al bond, which can be oxidized in situ with O2 or hydrolyzed. Furthermore, the obtained chiral cyclopentanes can be readily functionalized to provide various chiral compounds.


The Collaborative Lipid Research Clinics Program Family Study. I. Study design and description of data.
The third phase of the Lipid Research Clinics North American Population Studies is the Collaborative Family Study (1975-1978), designed to contribute knowledge of the familial association of dyslipoproteinemia and distribution of lipids and lipoproteins among family members. The 2,405 probands of the study were composed of a random (40%) and a hyperlipidemic (60%) component. A total of 15,693 living relatives of these probands were identified, of whom about 75% participated in the study. Demographic, medical, and medication history and lipid and lipoprotein data were collected with strict adherence to a common protocol and standardized laboratory methodology. This report presents the design and scope of the Family Study and the distribution of probands and relatives by clinic, age, selection scheme, and family structure. The possible avenues of analysis and the potential usefulness of this large, high quality data base in assessing the familial determinants of lipid and lipoprotein levels are discussed.


Alkali metal cation doped Al-SBA-15 for carbon dioxide adsorption.
Mesoporous aluminosilicate adsorbents for carbon dioxide were prepared by the grafting of aluminium into SBA-15 silica using an aqueous solution of aluminium chlorohydrate. As the ion exchange sites are primarily associated with the presence of tetrahedrally coordinated aluminium, extra-framework aluminium on the SBA-15 surface was inserted into the silica matrix by a treatment with an aqueous solution of NH(4)OH. Synthesized mesoporous aluminosilicate preserving all the characteristic features of a mesoporous molecular sieve was finally modified by the alkali metal cation exchange. To examine carbon dioxide adsorption on prepared materials, adsorption isotherms in the temperature range from 0 °C to 60 °C were measured. Based on the known temperature dependence of adsorption isotherms, isosteric adsorption heats giving information on the surface energetics of CO(2) adsorption were calculated and discussed. The comparison of carbon dioxide isotherms obtained on aluminosilicate SBA-15, aluminosilicate SBA-15 containing cations Na(+) and K(+) and activated alumina F-200 reveals that the doping with sodium or potassium cations dramatically enhances adsorption in the region of equilibrium pressures lower than 10 kPa. Therefore, synthesized aluminosilicate adsorbents doped with Na(+) or K(+) cations are suitable for carbon dioxide separation from dilute gas mixtures.


Refractory ocular hypertension secondary to intravitreal injection of triamcinolone acetonide.
to report a case of severe ocular hypertension occurring as a complication after a single intravitreal injection of triamcinolone acetonide for the treatment of a diabetic cystoid macular edema. interventional case report. a 63-year-old pseudophakic diabetic woman developed a severe and relatively sudden IOP increase to 50 mm Hg one month after receiving a single 4-mg intravitreal injection of triamcinolone acetonide for a chronic progressive macular cystoid edema. Previously the patient who did not develop corticosteroid-induced glaucoma secondary to her cataract surgery was treated with topical beta-blockers for a mild chronic bilateral ocular hypertension. A deep sclerectomy had to be performed in emergency to avoid optic nerve damage and allowed to successfully control the IOP with a 5 month follow-up. Concomitantly visual acuity could be increased from 0.05 before the intravitreal injection to 0.4. Although unfrequent in the literature, this observation confirms the risk of occurrence of a severe ocular hypertension after intravitreal injection of triamcinolone. A close monitoring of IOP is mandatory after intravitreal injection, especially in patients with altered trabecular function. This potentially devastating complication has to be weighed up with the benefices of intravitreal injection of triamcinolone for improving visual acuity in patients with clinically significant diabetic macular edema.


The prevalence and impact of brucellosis in patients with hepatitis delta virus infection: inside the Brucella outbreak with cirrhosis.
Hepatitis D virus (HDV) infection is a serious health problem leading to cirrhosis and hepatocellular carcinoma (HCC). Despite evidence that zoonotic infections are associated with end-stage liver disease, brucellosis in patients with delta hepatitis related to liver disease has not been well characterized. So, we examined this relationship using recent hospital-based data. We analyzed data from 96 delta hepatitis patients (mean age: 52.5 ±12.8 years; 50 male; 52 cirrhotics) and 117 (mean age: 50.4 ±7 years; 60 male) control subjects who were selected from patients with splenomegaly. The Brucella Wright test in connection with blood culture was used to detect active Brucella infection. Demographic features, laboratory data, results of ultrasonographic examination of the abdomen and Wright agglutination titers were compared between groups. There were 9 (9%) patients with active brucellosis in delta hepatitis patients. Compared to the control group, there was a statistically significant difference between groups in terms of having active brucellosis (9 vs. 2 patients; p < 0.001). Higher MELD scores were also associated with active Brucella infection (p < 0.005). Patients with chronic hepatitis D related cirrhosis (CHD-C) were at risk of developing brucellosis requiring hospitalization. Higher Wright titers among patients with more advanced liver disease may reflect a unique phenomenon that requires further investigation to determine underlying causative factors.


Phage cocktails - an emerging approach for the control of bacterial infection with major emphasis on foodborne pathogens.
Phage therapy has recently attracted a great deal of attention to counteract the rapid emergence of antibiotic-resistant bacteria. In comparison to monophage therapy, phage cocktails are typically used to treat individual and/or multi-bacterial infections since the bacterial agents are unlikely to become resistant as a result of exposure to multiple phages simultaneously. The bacteriolytic effect of phage cocktails may produce efficient killing effect in comparison to individual phage. However, multiple use of phages (complex cocktails) may lead to undesirable side effects such as dysbiosis, horizontal gene transfer, phage resistance, cross resistance, and/or higher cost of production. Cocktail formulation, therefore, representa compromise between limiting the complexity of the cocktail and achieving substantial bacterial load reduction towards the targeted host organisms. Despite some constraints, the applications of monophage therapy have been well documented in the literature. However, phage cocktails-based approaches and their role for the control of pathogens have not been well investigated. In this review, we discuss the principle of phage cocktail formulations, their optimization strategies, major phage cocktail preparations, and their efficacy in inactivating various food borne bacterial pathogens.


Silicone slings for the correction of ptosis associated with progressive external ophthalmoplegia.
Tarsofrontalis suspensions using silicone rods were performed in eleven patients for the ptosis associated with progressive external ophthalmoplegia. All patients had the eyelids elevated above the level of the pupils with resultant full field of vision and improved cosmesis. Patients have been followed for three to 24 months.


A pharmacist-led, American Heart Association Heart360 Web-enabled home blood pressure monitoring program.
To determine whether a pharmacist-led, Heart360-enabled, home blood pressure monitoring (HBPM) intervention improves blood pressure (BP) control compared with usual care (UC). This randomized, controlled trial was conducted in 10 Kaiser Permanente Colorado clinics. Overall, 348 patients with BP above recommended levels were randomized to the HBPM (n=175) or UC (n=173) groups. There were no statistically significant differences in baseline characteristics between the groups; however, there was a trend toward a higher baseline BP for the HBPM group compared with the UC group (148.8 versus 145.5 mm Hg for systolic BP; 89.6 versus 88.0 mm Hg for diastolic BP). At 6 months, the proportion of patients achieving BP goal was significantly higher in the HBPM group (54.1%) than in the UC group (35.4%; P<0.001). Compared with the UC group, the HBPM group experienced a -12.4-mm Hg larger (95% confidence interval, -16.3 to -8.6) reduction in systolic BP and a -5.7-mm Hg larger (95% confidence interval, -7.8 to -3.6) reduction in diastolic BP. The impact of the intervention on BP reduction was even larger for the subgroup of patients with diabetes mellitus or chronic kidney disease. The HBPM group had more e-mail and telephone contacts and greater medication regimen intensification. The proportion of patients reporting high satisfaction with hypertension care was significantly greater in the HBPM group (58%) than in the UC group (42%), P<0.001. A pharmacist-led, Heart360-supported, home BP monitoring intervention led to greater BP reductions, superior BP control, and higher patient satisfaction than UC.


Association of C-reactive protein and circulating leukocytes with resistance to Staphylococcus aureus infection in endotoxin-treated mice and rabbits.
The response of rabbits and mice to treatment with Escherichia coli endotoxin, as measured by C-reactive protein (CRP) and leukocyte levels, and resistance to Staphylococcus aureus infection was studied to evaluate the significance of these responses and their associations. In both species, there was an initial leukopenia without early recovery of normal lymphocyte levels. This was followed by an increase in polymorphonuclear leukocytes and a return to near the normal range. The CRP level was slightly altered during the stage of decreased resistance and increased throughout the remainder of the period of observation. The resistance level was decreased initially, recovered to normal levels, and continued to increase. The changes in CRP and resistance levels were closely associated. It would appear that this association between CRP and resistance, the antibacterial activity of CRP, and its action on the polysaccharides obtained from bacterial cell walls are evidence for the participation of CRP in nonspecific resistance to infection.


Perceptions of transcatheter device closure of patent ductus arteriosus in veterinary cardiology and evaluation of a canine model to simulate device placement: a preliminary study.
The purpose of this study was to evaluate a canine patent ductus arteriosus (PDA) model developed for practicing device placement and to determine practices and perceptions regarding transcatheter closure of PDA from the veterinary cardiology community. A silicone model was developed from images obtained from a dog with a PDA and device placement was performed with catheter equipment and a document camera to simulate fluoroscopy. A total of 36 individuals including 24 diplomates and 12 residents participated, and the feedback was obtained. The study included an initial questionnaire, practice with the model, observation of device placement using the model, and a follow-up questionnaire. A total of 92% of participants including 100% of residents indicated they did not have the opportunity to practice device placement before performing the procedure and obtained knowledge of the procedure from reading journal articles or observation. Participants indicated selecting the appropriate device size (30/36, 83%) and ensuring the device is appropriately positioned before release (18/36, 50%) as the most common areas of difficulty with device placement. Confidence level was higher after practicing with the model for residents when compared with diplomates and for participants that had performed 1-15 procedures when compared with those that had performed >15 procedures. These findings suggest those that have performed fewer procedures may benefit the most from practicing with a model. This preliminary study demonstrates the feasibility of a PDA model for practicing device placement and suggests that there is a potential benefit from providing additional training resources.


[Protective effects of Shenmai injection on intestinal mucosal barrier function in severely scalded rats].
To investigate the protective effects of shen-mai injection on intestinal barrier function in the early stage of 30% 3° scald, and to provide experimental basis for the prevention and control of enterogenic infection. A total of 60 Wistar rats were randomly divided into 6 groups: normal control group (without treatment), model control group (with 30% total body surface area (TBSA) fully thickness burn on the back), hexadecadrol (5 mg/kg) group, Shenmai injection (5, 10, 15 mg/kg) groups, with 10 rats in each group. After burned by scald apparatus, rats in each group were treated with drugs immediately by intraperitoneal injection once a day. At 72 hours after burned, the levels of plasma endotoxin, diamine oxidase (DAO), tumor necrosis factor-alpha (TNF-α), interleukins-6(IL-6) in all rats were detected and the mesenteric lymph nodes, liver and spleen were homogenized to culture for bacteria. The change of secretory immunoglobulin A (sIgA) in intestinal mucosa was measured. Compared with normal control group, bacterial translocation quantity in mesenteric lymph nodes(MLN), liver, and spleen, and the plasma levels of DAO, endotoxin, TNF-α, IL-6 and the level of sIgA in intestinal mucosa in model control group were increased significantly (P<0.01); compared with model control group, bacterial translocation quantity in MLN, liver, and spleen, and the plasma levels of DAO, endotoxin, TNF-α, IL-6 and the level of sIgA in intestinal mucosa in hexadecadrol (5 mg/kg) group and shen-mai injection (5, 10, 15 mg/kg) groups were decreased significantly (P<0.05 or P<0.01). Shen-mai injection can alleviate intestinal mucosa injury caused by severe scald, and the effects are similar with those of dexamethasone, and the effect is better in the high-dose group.


Construction of new primer sets for corresponding to genetic evolution of human adenoviruses in major capsid genes through frequent recombination.
A number of novel recombinant human adenoviruses (HAdVs) have recently been identified through sequencing of the complete genomes. The recombinant HAdV sequences share similarity with other types in the major capsid genes, namely the hexon, penton base, and fiber genes, implying recombination events, which may result in escape from the immune response and the acquisition of different organotropisms. Therefore, a surveillance system of HAdVs that considers the effect of frequent recombination on genetic evolution in these genes must be constructed. In this study, we designed new primer sets that can amplify the partial penton base and fiber genes from species HAdV-A to HAdV-F and proteotype HAdVs on the basis of sequence analyses, including previously reported primers that amplify loop 1 of the hexon. Phylogenetic analysis through sequencing with these primers correctly classified clinical HAdV isolates in loop 1 of the hexon gene, the Arg-Gly-Asp (RGD) loop of the penton base gene, and the knob of the fiber gene, which contain neutralizing, hemagglutination, and receptor binding epitopes associated with immunogenicity and tissue tropisms of HAdVs. This study contributes to the accumulation of correct information regarding genetic diversity and evolution in the worldwide HAdV surveillance.


192IrCl acid skin burn: case report and review of the literature.
A worker was contaminated following a chemical explosion that splashed an HNO3 radioactive solution containing approximately 180 MBq (5 mCi) 192Ir onto the left side of his face. Initial efforts reduced the contamination at least fivefold. Removal of a patch of contaminated hair was necessary. Most of the contamination was fixed to the skin; only a small amount of contamination was absorbed.


Effect of isoproterenol and propranolol on halothane MAD in dogs.
To evaluate the effect of propranolol on anesthetic requirement, changes in minimum alveolar concentration (MAC) of halothane accompanying acute (2 and 10 mg/kg IV) and chronic (200 mg/day orally for 10 days) propranolol administration were determined in dogs. MAC did not change significantly in either case. Beta-adrenergic blockade was achieved with the 2 mg/kg propranolol dose, as indicated by abolition of the pulse rate increase in response to isoproterenol infusion. Isoproterenol itself did not alter MAC. Mean arterial pressure (MAP) and heart rate (HR) at any given level of alveolar halothane were the same before and after chronic propranolol administration. Acute IV administration of propranolol, especially at the 10 mg/kg dose, reduced MAP and increased HR only transiently.


A New Extended Depth of Focus Intraocular Lens Based on Spherical Aberration.
To describe a new extended depth of focus intraocular lens (IOL) design offering multifocality by the variation of spherical aberration in the central optical zone. The new IOL (Mini WELL; SIFI, Catania, Italy) is an aspheric IOL with positive spherical aberration in the central 2-mm zone and negative spherical aberration in the pericentral 1-mm annulus, the amount of which was determined by specific optic calculation. The new IOL design was tested at the optical bench to investigate depth of focus and sensitivity to tilt, decentration, and angle Kappa. Visual acuity simulations were obtained from distance (4 m) to near (0.5 m). Modulation transfer function (MTF) for a 3-mm pupil was 0.35 to 0.40 for distance vision and 0.25 to 0.30 for intermediate and near vision. MTF for a 4.5-mm pupil was 0.40 to 0.55 and 0.10 to 0.20, respectively. These values were not influenced by tilt up to ±2.5°, by decentration up to ±0.5 mm, or by angle Kappa up to 9°. Visual acuity simulations indicated good visual acuity up to 2.00 D of pseudoaccommodation. The new IOL with double spherical aberration in the central 3-mm zone offered good MTF over a wide dioptric interval, suggesting good visual acuity between 4 m and 50 cm. This extended depth of focus IOL with no diffractive rings is expected to produce lower unwanted optical phenomena than current multifocal IOLs. [J Refract Surg. 2017;33(6):389-394.].


A dendritic cell vaccine induces protective immunity to intracranial growth of glioma.
The central nervous system is an immunologically privileged site hidden behind the blood brain barrier. Nevertheless, immune effector cells induced peripherally can be recruited into the central nervous system. Active immunotherapy of intracranial malignancies is thus potentially feasible. In this study we describe a vaccine regimen, based on bone marrow-derived dendritic cells pulsed with the RNA derived from GL261 glioma cells that induces a specific T cell response and protection against intracerebrally implanted GL261 tumors. Immunohistochemical analysis of brain tumors from vaccinated mice was characterized by pronounced intratumoral infiltrates predominantly of CD4+ as well as CD8+ T cells. The efficacy of the vaccine was improved further by administration of recombinant interleukin-12 into the vaccine regimen.


Therapeutic Risk Management for Violence: Safety Planning for Other-directed Violence.
Therapeutic management of risk for other-directed violence (ODV) involves screening, assessment, and clinically appropriate intervention. In this 5-part series, effective screening and assessment for ODV have been described as a combination of clinical interviewing and the use of structured tools to inform clinical impressions of both acute and chronic risk for violence. Once risk of violence is identified, therapeutic management of the risk throughout the course of treatment is best achieved by determining the function of the violent ideation and behavior. This can be achieved through the use of functional chain analysis. Chain analysis not only serves the purpose of providing insight into the contingencies of violent behavior but also helps to identify target areas of intervention where other skills, strategies, and means to access resources for support can be applied. In this fifth and final column of the series, we describe an intervention with all of these outcomes as its goals. A safety plan for ODV assists both clients and mental health professionals in disrupting patterns of violent ideation or behavior that would otherwise continue causing not only harm to others but prolonged negative consequences for those engaging in such behaviors.


[High school student and skin bleaching in Cameroon].
Introduction: Skin bleaching is a common practice in Africa, particularly in Cameroon. Studies show that it represents a danger for health, in terms of a demonstrated increased risk of dermatological diseases. However, increasing numbers of people are using skin bleaching in African cities, despite the fact that they are sometimes aware of the risk. This study proposed to transform the knowledge and perceptions of skin bleaching practices into educational strategies that can be used both by health professionals and educators. These strategies can also be used as preventive measures against skin bleaching among young schoolgirls. Methods: Data collection was based on a qualitative approach, in the form of a focus group discussion attended by 40 girls aged between 14 and 20 years, selected by convenient random sampling. Results: The results indicated that girls have an approximate knowledge about the consequences of skin bleaching on their health. On the contrary, they have a good knowledge about prevention, which can be used to develop a prevention strategy in order to reduce or eradicate skin bleaching, by educational awareness campaigns Conclusion: These elements can be used as a basis for better prevention and health promotion in schools; so that students adopt healthy behaviours and to prevent those students at risk.


Glucose-6-phosphate dehydrogenase activity in individual rat hepatocytes of different ploidy classes. II. Time-dependent variations during 24 h.
The time-dependent variation of glucose-6-phosphate dehydrogenase (G6PDH) activity during 24 h has been investigated by cytophotometric analysis in cytochemically stained, isolated hepatocytes of different ploidy classes from adult male rats. It was found that the amplitude of the variation in the total amount of parenchyma was 22%, with a maximum in the middle of the resting phase of the animals (13%). This small variation could not be detected subjectively in cryostat sections of liver that had been stained histochemically; nor could a metabolic zonation of the liver parenchyma be observed except the intermediate zone, which stained more strongly for G6PDH activity at 13% and 22%. The quantitative study on the isolated hepatocytes, however, revealed a relatively strong variation of 48% during the day in enzyme activity of the mononuclear diploid cells and no significant variation in the binuclear tetraploid cells. The cells of the in-between ploidy classes showed an amplitude of variation of 38% (binuclear diploid cells) and 24% (mononuclear tetraploid cells). All cells showed a maximum activity at 13% and a minimum activity during the night. It is concluded that this ploidy-dependent variation might play a role in the generation of pentoses for RNA synthesis. The findings indicate that for metabolic studies the heterogeneity of the liver parenchyma should be taken into account with respect to the different ploidy classes, as well as the well-known metabolic zonation of the acinus.


Periodontal status of maxillary central incisors after orthodontic traction: a longitudinal follow-up.
The aim of this study was to evaluate the clinical and radiographic periodontal status of impacted permanent maxillary central incisors (Mx.1) after a long term of orthodontic traction. This split-mouth study evaluated a sample of 11 patients (five females, six males) treated with Mx.1 unilateral traction one to 28 years after the removal of orthodontic appliances. The traction Group (TG) consisted of 11 Mx.1 and the Comparison Group (CG) comprised 11 spontaneously erupted contralateral Mx.1. High-resolution CBCT exams of central incisors were performed using Accuitomo (J. Morita, Kyoto, Japan). Cross-section imagens passing through the center of maxillary central incisors were used to measure buccal and lingual alveolar bone level. Presence of fenestration, root dilacerations, root coverage, and position of the root apex were also assessed in the same images. Clinical parameters included periodontal probing depth, attachment level, gingival bleeding index, plaque index, degree of gingival recession, amount of gingival mucosa, and evaluation of interproximal papilla and black triangle. Digital model analysis included an assessment of clinical crown height and width. Intergroup comparisons were performed using paired t-, McNemar's, and Wilcoxon tests (p<0.05). Compared to CG, we found a significantly thinner labial bone plate thickness in TG at the middle (p=0.000) and apical (p=0.009) root level. We also observed an apical displaced labial bone crest level in TG (p=0.000). The Traction Group showed a greater frequency of root dilacerations and gingival recessions, a decreased amount of keratinized mucosa, and a decreased clinical attachment level at the labial aspect compared to contralateral teeth. A decreased thickness and height of labial alveolar bone and gingival recessions were found in maxillary central incisors 15 years after orthodontic traction. Though incisor traction might cause some periodontal impact, differences are acceptable under a clinical point of view considering the cost-benefit ratio.


Lidocaine relieves murine allergic rhinitis by regulating the NF-κB and p38 MAPK pathways.
Allergic rhinitis (AR) is one of the most common chronic inflammatory diseases and its main feature is nasal mucositis. It has been recently revealed that lidocaine demonstrates optimal effects in the treatment of various diseases. However, a limited number of studies have examined the association between lidocaine and AR. In the present study, the AR mouse model was established to explore the effects of lidocaine in AR and to further analyze its molecular mechanism. Subsequently, different concentrations of lidocaine were provided to the animals by intranasal administration and a series of indices were assessed. The data indicated that the frequencies of mouse sneezing and nose rubbing were suppressed following an increase in lidocaine concentration. Subsequently, the number of inflammatory cells was measured. Wright's-Giemsa staining results indicated that lidocaine significantly decreased the numbers of leukocytes, eosinophils, neutrophils and lymphocytes in the nasal lavage fluid (NLF) of AR mice. In addition, the expression levels of ovalbumin (OVA)-specific immunoglobulin E (IgE), leukotriene C4 (LTC4) and certain inflammatory factors were assessed by ELISA. Lidocaine reduced OVA-specific IgE and LTC4 expression in NLF and plasma derived from AR mice. It also decreased the expression levels of IL-4, IL-5, IL-13, IL-17 and TNF-α. Lidocaine caused upregulation of IFN-γ and IL-2 expression levels. Subsequently, western blot analysis indicated that lidocaine suppressed phosphorylated (p)-p38 and p-p65 expression levels in AR mice. Collectively, the results indicated that the NF-κB and p38 MAPK signaling pathways were involved in the lidocaine-mediated relief of AR in mice. In order to further verify the association between the NF-κB and p38 MAPK signaling pathways and AR in mice, the effects of the NF-κB inhibitor IMD-0354 and the p38 MAPK inhibitor SB 203580 were assessed on AR mice. The results indicated that these two compounds exhibited similar inhibitory effects on AR mice as those noted with the use of lidocaine. These findings suggested that lidocaine represented a novel therapeutic agent for AR.


Mental health and substance use disorder comorbidities among Medicaid beneficiaries: Associations with opioid use disorder and prescription opioid misuse.
Medicaid presently insures about one-fourth of the US population and disproportionately insures about 38 % of non-elderly adults with an opioid use disorder (OUD). Owing to Medicaid's prominent role insuring persons with an OUD and that Medicaid coverage includes pharmaceutical benefits, there has been considerable interest in studying potential prescription opioid misuse among Medicaid beneficiaries and identifying subpopulations at higher risk for misuse and possible progression to an OUD. The study goals were to explore the associations among prescription opioid misuse, OUD, and co-occurring mental health and other substance use disorders (SUD). We analyzed Illinois Medicaid 2018 claims data for 1102479 adult beneficiaries 18 to 64 years of age. Using algorithms based on previous studies, we first determined either the presence or absence of nine SUDS (including OUD), nine mental health disorders and likely prescription opioid misuse. Then, we subdivided the beneficiary sample into five groups: those who were prescribed opioids and evidenced either no, possible, or probable misuse; those evidencing an OUD; and those evidencing no opioid use or misuse. Bivariate analyses, upset plots, and multinomial logistic regressions were used to compare the five subgroups on the prevalence of co-occurring SUDS and mental health disorders. Those with an OUD or with probable prescription opioid misuse had the highest prevalence of most co-occurring conditions with beneficiaries with an OUD the most likely to evidence co-occurring SUDS, particularly tobacco use disorder, whereas those with probable misuse had elevated prevalence rates of co-occurring mental health disorders comparable to those with an OUD. The medical complexity of persons with an OUD or misusing prescription opioids are considered in light of recent attempts to expand buprenorphine provision as a medication for OUD among Medicaid beneficiaries. Additionally, we consider the possibility of gender, co-occurring mental health disorders, and tobacco use disorder as important risk factors for progressing to prescription opioid misuse and an OUD.


Inflammation-free, gas-permeable, lightweight, stretchable on-skin electronics with nanomeshes.
Thin-film electronic devices can be integrated with skin for health monitoring and/or for interfacing with machines. Minimal invasiveness is highly desirable when applying wearable electronics directly onto human skin. However, manufacturing such on-skin electronics on planar substrates results in limited gas permeability. Therefore, it is necessary to systematically investigate their long-term physiological and psychological effects. As a demonstration of substrate-free electronics, here we show the successful fabrication of inflammation-free, highly gas-permeable, ultrathin, lightweight and stretchable sensors that can be directly laminated onto human skin for long periods of time, realized with a conductive nanomesh structure. A one-week skin patch test revealed that the risk of inflammation caused by on-skin sensors can be significantly suppressed by using the nanomesh sensors. Furthermore, a wireless system that can detect touch, temperature and pressure is successfully demonstrated using a nanomesh with excellent mechanical durability. In addition, electromyogram recordings were successfully taken with minimal discomfort to the user.


Optimization of Nutrient-Rich Ice Plant (Mesembryanthemum crystallinum L.) Paste Fresh Noodle Pasta Using Response Surface Methodology.
The ice plant is a species that is grown mainly in the dry regions of the American West and contains various minerals and ingredients beneficial for human health, such as inositol and beta-carotene. With the growing trend towards healthy foods, pasta consumption has also increased. Pasta is a convenient and low-glycemic-index food that is composed mainly of carbohydrates, proteins, lipids, dietary fiber, and trace amounts of minerals. The optimal mixing ratio was evaluated to produce pasta of the highest quality in terms of blood sugar elevation and antioxidant efficacy. The components and minerals of the ice plant, including D-pinitol and inositol, were analyzed, and 20 essential amino acids were identified. In this study, we also investigated the quality and characteristics of ice plant paste and eggs, as well as the quality, antioxidant activity, and formulation of raw materials mixed with ice plant at different ratios. Optimal conditions were found to be 46.73 g of ice plant paste in 100 g of durum wheat flour, 20.23 g of egg, and 2 g of salt, providing a way to develop fresh pasta that enhances the health benefits of ice plant paste without excessive moisture and other ingredients.


Optimization by Adaptive Stochastic Descent.
When standard optimization methods fail to find a satisfactory solution for a parameter fitting problem, a tempting recourse is to adjust parameters manually. While tedious, this approach can be surprisingly powerful in terms of achieving optimal or near-optimal solutions. This paper outlines an optimization algorithm, Adaptive Stochastic Descent (ASD), that has been designed to replicate the essential aspects of manual parameter fitting in an automated way. Specifically, ASD uses simple principles to form probabilistic assumptions about (a) which parameters have the greatest effect on the objective function, and (b) optimal step sizes for each parameter. We show that for a certain class of optimization problems (namely, those with a moderate to large number of scalar parameter dimensions, especially if some dimensions are more important than others), ASD is capable of minimizing the objective function with far fewer function evaluations than classic optimization methods, such as the Nelder-Mead nonlinear simplex, Levenberg-Marquardt gradient descent, simulated annealing, and genetic algorithms. As a case study, we show that ASD outperforms standard algorithms when used to determine how resources should be allocated in order to minimize new HIV infections in Swaziland.


Synthesis of [Glu34]human splenin (hSP) and examination of its immunological effect on the reduced B-lymphocytes of uremic patients.
[Glu34]human splenin (hSP) was synthesized in a conventional manner by assembling ten peptide fragments followed by deprotection with 1 M trifluoromethanesulfonic acid-thioanisole (molar ratio, 1:1) in trifluoroacetic acid in the presence of m-cresol and dimethylselenide. Finally, the deprotected peptide was incubated with dithiothreitol to reduce sulfoxide on the methionine side chain. Incubation of peripheral lymphocytes isolated from uremic patients with the synthetic [Glu34]hSP showed an enhancing effect on the reduced B-lymphocytes, but synthetic human thymopoietin (hTP) had no effect under the same conditions.