Altered response to inflammatory cytokines in hepatic energy metabolism in inducible nitric oxide synthase knockout mice

BACKGROUND/AIMS: Production of nitric oxide (NO) in the liver is believed to be a critical factor for carbohydrate and energy metabolism in endotoxin shock. The present study focuses on the involvement of NO produced by inducible nitric oxide synthase (iNOS) in glycogen synthesis and energy metabolism stimulated by insulin.METHODS: Primary hepatocytes prepared from wild-type and iNOS knockout (iNOS(-/-)) mice were employed.RESULTS: Incubation of wild-type hepatocytes with a combination of cytokines (interleukin-1beta, tumor necrosis factor-alpha and interferon-gamma) and lipopolysaccharide (cytokines/LPS) inhibited insulin-stimulated glycogen synthesis and adenosine triphosphate (ATP) increase, and decreased the ketone body ratio (KBR) at 8-12 h, concomitant with expression of iNOS protein and NO production. While the glycogen synthesis was suppressed by cytokines/LPS, reduction of the ATP increase and a decrease in KBR by cytokines/LPS were not observed in iNOS(-/-) hepatocytes. Further, N(G)-monomethyl-L-arginine, a NOS inhibitor, reversed the inhibition of ATP increase and decrease in KBR by cytokines/LPS, but not the inhibition of glycogen synthesis. Conversely, addition of S-nitroso-N-acetylpenicillamine, a NO donor, inhibited the insulin-stimulated ATP increase synthesis in iNOS(-/-) hepatocytes, but not the insulin-stimulated glycogen synthesis.CONCLUSIONS: These results demonstrate that NO mediates the suppression of insulin-stimulated energy metabolism, but not glycogen synthesis, in cytokines/LPS-treated hepatocytes.     

Dual-Channel Photoplethysmography to Monitor Local Changes in Vascular Stiffness

Objectives. Monitoring arterial distensibility changes is important to understand the cardiovascular status of patient. Pulse transit time (PTT), which is an inverse equivalent of pulse wave velocity (PWV), has shown its potential in such studies. However, its methodological approach in using an electrocardiogram and a peripheral photoplethysmography (PPG) is limited due to the inclusion of pre-ejection period (PEP) in its computation. Previous studies have suggested the using the transit time difference between two peripheral measuring sites (PTT-D) instead. However, it requires two medical instruments and may not be efficient in terms of equipment utility, especially in prolonged clinical studies. Methods. Postural changes are known to cause complex haemodynamics adaptation and thereby affecting transit time measurements. A customised dual-channel PPG system based on discrete electronic devices was constructed to evaluate against conventional peripheral-based PTT. 10 healthy adults (7 male; mean age 27.0 yr) were recruited to assess the differences observed in PTT and PTT-D during two postural change test activities. Results. PTT-D derived from the customised PPG system registered 43.3± 5.6 ms and − 31.1± 3.8 msrelativechangesforthetworegulatedactivitieswhileconventionalPTTrecorded 43.6± 10.3 msand -31.0±m 6.5 msrespectively. Theformermayhavesimilarresultsbuthavesignificantlylowervariance (< EmphasisType =Italic p </Emphasis 0.05). Conclusions. Findings herein suggest that PTT-D derived from the customised PPG system shows potential. It can be used as an alternative to conventional peripheral-based PTT and possibly as a direct assessment of arterial distensibility or PWV variations as it does not include PEP in its time-related computations.     

Unscheduled Return Visits With and Without Admission Post Emergency Department Discharge

Background

Monitoring unscheduled return visits to the Emergency Department (ED) is useful to identify medical errors.

Objective

To investigate the differences between unscheduled return visit admissions (URVA) and unscheduled return visit no admissions (URVNA) after ED discharge.

Methods

From January 1, 2008 to March 31, 2008, URVA and URVNA patients who returned within 3 days after ED discharge were enrolled in the study. We compared the clinical characteristics, underlying diseases, ED crowding indicators, staff experience at the patient's first visit, and several other risk factors. We used multivariate logistic regression to evaluate differences between the two groups and to identify predictors of admission from unscheduled return visits.

Results

The unscheduled return visit rate was 3.1%. Of the 413 patients included, 147 patients (36%) were admitted, and had a mortality rate of 4.1%. The most common reason for the return visit was an illness-based factor (47.9%). Compared to URVNA patients, unscheduled return visit admissions had higher prevalence rates for old age, non-ambulatory status, high-grade triage, and underlying diseases (e.g., malignancy, diabetes mellitus, hypertension, coronary artery disease, heart failure, and chronic obstructive pulmonary disease). The independent predictors for URVA were: age ≥ 65 years (adjusted odds ratio [OR] 2.2, 95% confidence interval [CI] 1.4–3.5); high-grade triage (adjusted OR 2.1, 95% CI 1.3–3.2); and doctor-based factors (adjusted OR 3.5, 95% CI 2.0–6.1). More advanced staff experience (p = 0.490) and ED crowding were not significant predictors (p = 0.498 for whole-day number of patients, p = 0.095 for whole-shift number of patients).

Conclusion

Old age, high-grade triage, and doctor-based factors were found to be significant predictors for URVA, whereas advanced staff experience and ED crowding were not.     

Development of hydrophobic reduced graphene oxide as a new efficient approach for photochemotherapy

Nowadays, chemotherapy is one of the crucial and common therapies in the world. So far, it has been revealed to be highly promising, yet patients suffer from the consequences of severe negative medical dosages. In order to overcome these issues, the enhancement of photothermal chemotherapy with reduced graphene oxide (rGO) as a photothermal agent (PTA) is widely utilised in current medical technologies. This is due to its high near-infrared region (NIR) response, in vitro or in vivo organism biocompatibility, low risk of side effects, and effective positive results. Moreover, rGO not only has the ability to ensure that selective cancer cells have a higher mortality rate but can also improve the growth rate of recovering tissues that are untouched by necrosis and apoptosis. These two pathways are specific diverse modalities of cell death that are distinguished by cell membrane disruption and deoxyribonucleic acid (DNA) disintegration of the membrane via phosphatidylserine exposure in the absence of cell membrane damage. Therefore, this review aimed to demonstrate the recent achievements in the modification of rGO nanoparticles as a PTA as well as present a new approach for performing photochemotherapy in the clinical setting.

rGO of QD-rGO nanocomposite could absorb and convert into heat when harvested under NIR radiation, resulting cell death with reduction of fluorescence.     

Age-Related Hip Proprioception Declines: Effects on Postural Sway and Dynamic Balance

Objective

To evaluate the effects of age on hip proprioception, and determine whether age-related hip proprioception declines disrupt balance.

Design

Survey of proprioception and balance differences between 3 age groups.

Setting

University balance laboratory.

Participants

Volunteer sample of independent community-dwelling adults (N=102) without sensory or other neurologic impairments in 3 age groups: younger (mean age, 24.6y; range, 19–37y), mid-aged (mean age, 53.3y; range, 40–64y), and older adults (mean age, 76.3y; range, 65–94y).

Interventions

Not applicable.

Main Outcome Measures

Hip joint position sense (JPS) and kinesthesia were measured using a custom-built device. JPS error was determined by the magnitude of matching errors during vision and no-vision conditions. Kinesthesia was evaluated by the ability to detect passive limb rotation without vision. Postural sway was assessed during static stance and measured using root mean square of center of pressure (COP) displacement and velocity of COP displacement. Clinical balance and fear of falling were assessed with the mini-Balance Evaluation Systems Test (mini-BESTest) and Activities-specific Balance Confidence Scale, respectively.

Results

Both older and mid-aged adults had significantly increased JPS error compared with younger adults (P<.05). Kinesthesia accuracy was significantly decreased in older adults compared with mid-aged and younger adults (P≤.01). Both measures of proprioception error correlated with age (P≤.001). There were no relationships between hip proprioception error and postural sway during static stance. However, older adults with lower proprioceptive error had significantly higher mini-BESTest scores of dynamic balance abilities (P=.005).

Conclusions

These results provide evidence of significant hip proprioception declines with age. Although these declines are not related to increases in postural sway, participants with hip proprioception declines demonstrated disrupted dynamic balance, as indicated by decreased mini-BESTest scores.     

Legume genome evolution viewed through the Medicago truncatula and Lotus japonicus genomes

Genome sequencing of the model legumes, Medicago truncatula and Lotus japonicus, provides an opportunity for large-scale sequence-based comparison of two genomes in the same plant family. Here we report synteny comparisons between these species, including details about chromosome relationships, large-scale synteny blocks, microsynteny within blocks, and genome regions lacking clear correspondence. The Lotus and Medicago genomes share a minimum of 10 large-scale synteny blocks, each with substantial collinearity and frequently extending the length of whole chromosome arms. The proportion of genes syntenic and collinear within each synteny block is relatively homogeneous. Medicago-Lotus comparisons also indicate similar and largely homogeneous gene densities, although gene-containing regions in Mt occupy 20-30% more space than Lj counterparts, primarily because of larger numbers of Mt retrotransposons. Because the interpretation of genome comparisons is complicated by large-scale genome duplications, we describe synteny, synonymous substitutions and phylogenetic analyses to identify and date a probable whole-genome duplication event. There is no direct evidence for any recent large-scale genome duplication in either Medicago or Lotus but instead a duplication predating speciation. Phylogenetic comparisons place this duplication within the Rosid I clade, clearly after the split between legumes and Salicaceae (poplar).     

High risk of Mycobacterium tuberculosis infection during the Hajj pilgrimage

INTRODUCTION: Annually more than 2 million pilgrims from all over the world attend the Hajj in Saudi Arabia. Overcrowding during this pilgrimage leads to a high risk of transmission of airborne infectious diseases. Tuberculosis (TB) is common among hospitalized pilgrims, but the overall risk of acquiring Mycobacterium tuberculosis infection during this pilgrimage is not known. We conducted a prospective study to assess the risk of M. tuberculosis infection among Hajj pilgrims. METHODS: We measured the immune response to TB antigens using a whole-blood assay (QuantiFERON TB assay) prior to departure and 3 months after return from the Hajj pilgrimage. RESULTS: Of 357 paired assays, 149 pilgrims were negative prior to the Hajj and 15 (10%) of these had a significant rise in immune response to TB antigens. CONCLUSIONS: Pilgrims may be at high risk of acquiring M. tuberculosis infection during the Hajj. This has significant public health implications for TB control in countries with large Muslim populations.     

Familial hyperamylasaemia.

A six year old boy underwent extensive investigation for recurrent abdominal pain and was found to have a persistently raised serum amylase. Endoscopic retrograde cholangiopancreatography was normal and macroamylasaemia was excluded. Serum amylase concentrations were found to be raised in other family members spanning three generations, all of whom were asymptomatic. Clearance studies suggested no evidence of a renal tubular defect and serum lipase concentrations were normal. This is the first report of apparently familial hyperamylasaemia and the mode of inheritance is consistent with an autosomal dominant pattern.     

Does the use of mean or median Z-score of the thyroid volume indices provide a more precise description of the iodine deficiency disorder status of a population?

Endemic iodine deficiency is largely an environmental problem affecting whole populations. Currently, thyroid volume data from a population are analyzed with the sole objective of obtaining an estimate of goitre prevalence using +97th percentile or +2 standard deviations of an appropriate reference as cut-off. This paper proposes an alternative approach to the analysis and presentation of thyroid volume data using Z-scores (standard deviation scores) of the thyroid volume indices such as thyroid volume-for-age or thyroid volume-for-body surface area. The calculation of the summary statistics of the Z-scores, such as mean or median, provides an alternative to the prevalence-based approach for expressing severity of iodine deficiency disorders (IDD). An advantage of the mean or median Z-score is that it describes the thyroid volume profile (and therefore the IDD status) of the entire population directly, unlike goitre prevalence which gives information only about the extremes of distribution. The frequency curve or histogram of the Z-scores provides a complete picture of the whole distribution. Although qualitatively similar conclusions on IDD severity can be drawn from both analytical approaches, only the Z-score system is able to capture adequately the trends or changes in thyroid size over time, and to establish whether a previously iodine-deficient community's thyroid volume profile has returned to 'normal' (as indicated by a distribution that is not significantly different from that of the reference) following intervention. As a continuous variable, Z-scores are particularly useful for the analysis of data from populations where the sample size is relatively small, or where many individuals lie outside the extreme percentiles of the reference population. In view of its advantages in the context of activities based on single and multiple measurements, the Z-score system is to be preferred for the reporting and use of thyroid volume indices. A desirable consequence of this preference is that national goals will be oriented towards an improvement of the overall thyroid volume profile of the population, rather than just a reduction of the number of individuals at the extremes.