The effect of Mediterranean diet on inflammatory biomarkers and components of metabolic syndrome in adolescent girls.

BACKGROUND: The prevalence of obesity and metabolic syndrome (MetS) during childhood and adolescence is rising significantly worldwide. Previous studies have shown that following a healthy dietary pattern, like the Mediterranean diet (MD), might be an efficacious approach for the prevention and management of MetS during childhood. In the present study, we aimed to examine the effect of MD on inflammatory markers and components of MetS among adolescent girls with MetS. METHODS: This randomized controlled clinical trial was conducted on 70 girl adolescents with metabolic syndrome. Patients in the intervention group followed a prescribed MD, while participants in the control group received dietary advice according to the food pyramid. The length of intervention was 12 weeks. Participants' dietary intakes were evaluated using three 1-day food records throughout the study. Anthropometric measures, inflammatory markers, systolic and diastolic blood pressure, and hematological factors were assessed at the baseline and end of the trial. An intention-to-treat approach was taken into account for the statistical analysis. RESULTS: After 12 weeks, participants in the intervention group had lower weight (Ptime*group ≤ 0/001), body mass index (BMI) (Ptime*group ≤ 0/001), and waist circumference (WC) (Ptime*group ≤ 0/001) compared with those in the control group. In addition, MD resulted in a significantly reduced systolic blood pressure compared to the those in the control group (Ptime*group ≤ 0/001). In terms of metabolic variables, MD led to a significant decrease in fasting blood glucose (FBS) (Ptime*group ≤ 0/001), triglycerides (TG) (Ptime*group ≤ 0/001), low-density lipoprotein (LDL) (Ptime*group ≤ 0/001), homeostatic model assessment of insulin resistance (HOMA-IR) (Ptime*group = 0/02) and a meaningful increase in serum levels of high-density lipoprotein (HDL) (Ptime*group ≤ 0/001). In addition, adherence to the MD resulted in a significant reduction in serum levels of inflammatory markers including Interleukin 6 (IL-6) (Ptime*group = 0/02) and high-sensitivity C-reactive protein (hs-CRP) (Ptime*group = 0/02). However, no significant effect was seen on serum levels of tumor necrosis factor α (TNF-α) (Ptime*group = 0/43). CONCLUSION: Overall, the findings of the present study revealed that consumption of MD for 12 weeks resulted in a favorable effect on anthropometric measures, components of MetS, as well as on some inflammatory biomarkers.

Responses of some matrix metalloproteinases activities to an acute session of endurance exercise and electrical stimulation in induced myocardial infarction in Wistar rats.

OBJECTIVE: Myocardial infarction is the irreversible cell death of cardiac muscle that takes place after the blood flow is cut off to a specific region of the heart muscle. The molecular angiogenesis process that may follow after the incidence, due to any activity or its intensity, is unknown. The purpose of this research was to examine some of the matrix metalloproteinase (MMP) responses to an acute course of endurance exercise and electrical stimulation in induced myocardial infarcted Wistar rats. MATERIALS AND METHODS: In this experimental case-control study, 40 induced myocardial infarcted Wistar rats (8-week-old, mean weight 130±30 g) were randomly assigned into 4 conditions: endurance exercise, exercise + electrical stimulation, only electrical stimulation, and control group. The infarction was induced 24 hours after the subcutaneous injection of 150 mg/kg of Isoproterenol. The exercise and exercise plus electrical stimulation groups performed a session of endurance exercise on an animal treadmill, at 20 m/min for one hour. The electrical stimulation was delivered by foot shock, set with the intensities of 0.5 mA for 20 minutes. Immediately after the cessation of the treatment protocol, MMP1, MMP2, and MMP9 were measured by the ELISA method. Data analysis was performed by using Two-way ANOVA and significance was set at α = 0.05. RESULTS: One session of endurance exercise or electric stimulation, or their combination, had no significant effect on the level of MMPs. CONCLUSIONS: One session of acute endurance exercise, stimulation, or their combination, elicited no significant effect on the level of MMPs of artificially induced myocardial infarcted Wistar rats.

A Systematic Review and Meta-analysis of the Medical Error Rate in Iran: 2005-2019.

BACKGROUND AND OBJECTIVES: Medical errors (MEs) are one of the main factors affecting the quality of hospital services and reducing patient safety in health care systems, especially in developing countries. The aim of this study was to determine the rate of ME in Iran. METHODS: This is a systematic literature review and meta-analysis of extracted data. The databases MEDLINE, EMBASE, Scopus, Cochrane, SID, Magiran, and Medlib were searched in Persian and English, using a combination of medical subject heading terms ("Medical Error" [Mesh] OR "Medication error" [Mesh] OR "Hospital Error" AND ("Iran" [Mesh]) for observational and interventional studies that reported ME rate in Iran from January 1995 to April 2019. We followed the STROBE checklist for the purpose of this review. RESULTS: The search yielded a total of 435 records, of which 74 articles were included in the systematic review. The rate of MEs in Iran was determined as 0.35%. The rates of errors among physicians and nurses were 31% and 37%, respectively. The error rates during the medication process, including prescription, recording, and administration, were 31%, 27%, and 35%, respectively. Also, incidence of MEs in night shifts was higher than in any other shift (odds ratio [OR] = 38%; 95% confidence interval [CI]: 31%-45%). Moreover, newer nurses were responsible for more errors within hospitals than other nurses (OR = 57%; 95% CI: 41%-80%). The rate of reported error after the Health Transformation Plan was higher than before the Health Transformation Plan (OR = 40%; CI: 33%-49% vs OR = 30%; CI: 25%-35%). CONCLUSION: This systematic review has demonstrated the high ME rate in Iranian hospitals. Based on the error rate attributed solely to night shifts, more attention to the holistic treatment process is required. Errors can be decreased through a variety of strategies, such as training clinical and support staff regarding safe practices and updating and adapting systems and technologies.

Statistical power or more precise insights into neuro-temporal dynamics? Assessing the benefits of rapid temporal sampling in fMRI.

Functional magnetic resonance imaging (fMRI), a non-invasive and widely used human neuroimaging method, is most known for its spatial precision. However, there is a growing interest in its temporal sensitivity. This is despite the temporal blurring of neuronal events by the blood oxygen level dependent (BOLD) signal, the peak of which lags neuronal firing by 4-6 seconds. Given this, the goal of this review is to answer a seemingly simple question - "What are the benefits of increased temporal sampling for fMRI?". To answer this, we have combined fMRI data collected at multiple temporal scales, from 323 to 1000 milliseconds, with a review of both historical and contemporary temporal literature. After a brief discussion of technological developments that have rekindled interest in temporal research, we next consider the potential statistical and methodological benefits. Most importantly, we explore how fast fMRI can uncover previously unobserved neuro-temporal dynamics - effects that are entirely missed when sampling at conventional 1 to 2 second rates. With the intrinsic link between space and time in fMRI, this temporal renaissance also delivers improvements in spatial precision. Far from producing only statistical gains, the array of benefits suggest that the continued temporal work is worth the effort.

Signal transduction in electrically stimulated articular chondrocytes involves translocation of extracellular calcium through voltage-gated channels.

OBJECTIVE: To ascertain, using specific inhibitors, the potential role of calcium-related signal transduction pathways in the mechanism of cartilage matrix protein gene induction and metalloproteinase gene suppression by capacitively coupled electric fields. METHODS: Articular chondrocytes were isolated from adult bovine patellae and cultured in high density for 7 days. To study matrix protein expression, cells cultured in the absence or presence of specific calcium pathway inhibitors were exposed to a capacitively coupled electrical field (60 kHz, 20 mV/cm): for aggrecan 1h at 50% duty cycle and for type II collagen 6h at 8.3% duty cycle. To study metalloproteinase expression in the presence of interleukin 1 beta (IL-1beta), cells were cultured as above but exposed for only 30 min to a 100% duty cycle signal. At harvest, total mRNA was isolated and aggrecan, type II collagen, matrix metalloproteinase (MMP-1, -3 and -13) and aggrecanase [a disintegrin and metalloproteinase with thrombospondin repeats (ADAMTS-4 and -5)] mRNA expression were measured by quantitative real-time polymerase chain reaction (qPCR). RESULTS: (1) In the absence of inhibitors, appropriate electrical stimulation induces a 3-4-fold up-regulation of both aggrecan and type II collagen mRNA and a 3.7-9.6-fold down-regulation of IL-1beta-induced metalloproteinases; (2) the presence of inhibitors alone does not affect any target mRNA levels; (3) inhibitors of intracellular calcium regulation and inositol 1,4,5-triphosphate (IP(3)) formation [8-(diethylamino)octyl-3,4,5,-trimethoxybenzoate hydrochloride (TMB-8) and neomycin, respectively] have no effect on regulation of target mRNA levels by electrical stimulation; and (4) inhibitors of voltage-gated calcium channels (verapamil), calmodulin activation (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride, W-7), calcineurin activity (cyclosporin A), phospholipase C activity (bromophenacyl bromide, BPB) and prostaglandin E(2) (PGE(2)) synthesis (indomethacin) completely inhibit the effects of electrical stimulation. CONCLUSIONS: The results are consistent with the effects of electrical stimulation involving a pathway of extracellular Ca(2+) influx via voltage-gated calcium channels rather than from intracellular Ca(2+) repositories; and with downstream roles for calmodulin, calcineurin and nuclear factor of activated T-cells (NF-AT) rather than for phospholipase C and IP(3).

Location and identification of the collagen found in the 14.5-d rat embryo visceral yolk sac.

The collagens associated with 14.5-d rat visceral yolk sacs were localized and identified by a variety of procedures. Morphological examination showed that both the visceral epithelium and mesothelium rested upon thin basement membranes, whereas the majority of the extracellular matrix consisted of a stroma containing occasional cells and abundant banded fibrils. Immunohistochemistry at the electron microscope level showed that the basement membranes specifically cross-reacted with antibodies directed against mouse basement membrane components, whereas the stroma specifically cross-reacted with antibodies directed against rat type I collagen. Extractions of acellular visceral yolk sacs and subsequent analyses showed that type I collagen components were prevalent. Furthermore, in vitro biosynthetic studies showed only the presence of type I procollagen components (or their conversion products) and alpha-fetoprotein. These findings, taken together with our previous studies on the 14.5-d rat parietal yolk sac, provide us with protein markers for studying the origin of cells in rat parietovisceral yolk sac carcinomas.

Deposition of fibronectin and laminin in the basement membrane of the rat parietal yolk sac: immunohistochemical and biosynthetic studies.

Rat parietal yolk sacs (PYS) at gestational ages 7.5, 9.5, 11.5, 13.5, 14.5, and 16.5 d were reacted with antibodies against laminin or plasma fibronectin. At all times studied, laminin consistently gave a positive reaction with Reichert's membrane and with the cytoplasm of PYS cells. In contrast, fibronectin gave a negative reaction with Reichert's membrane at day 7.5, was weakly positive at day 9.5, and from then on was increasingly positive with maximum reactivity at 14.5 d. By electron microscopic immunohistochemistry, antilaminin reacted strongly with 14.5-d Reichert's membrane and with the contents of the rough endoplasmic reticulum RER cisternae of the PYS cells. Antifibronectin had some spotty reactivity with Reichert's membrane, but the cytoplasm of the PYS cells was negative. The contents of the vitelline vessels and the interface between trophoblast and Reichert's membrane were strongly positive. Metabolic labeling of PYS cells in organ culture clearly demonstrated the presence of laminin, type IV procollagen, and entactin both in the medium and in tissues, but fibronectin was absent. No component in the medium bound to gelatin-Sepharose columns. These studies demonstrate that PYS cells, which actively synthesize and secrete basement membrane components, do not synthesize any detectable fibronectin. Furthermore, the anti-fibronectin staining pattern in the vitelline vessels and trophoblast-Reichert's membrane interface strongly suggests that the fibronectin present in Reichert's membrane is derived from the maternal circulation and is merely "trapped" in the membrane.

Factor XII truncation accelerates activation in solution.

Essentials During contact system activation, factor XII is progressively cleaved by plasma kallikrein. We investigated the role of factor XII truncation in biochemical studies. Factor XII contains naturally occurring truncating cleavage sites for a variety of enzymes. Truncation of factor XII primes it for activation in solution through exposure of R353. SUMMARY: Background The contact activation system and innate immune system are interlinked in inflammatory pathology. Plasma kallikrein (PKa) is held responsible for the stepwise processing of factor XII (FXII). A first cleavage activates FXII (into FXIIa); subsequent cleavages truncate it. This truncation eliminates its surface-binding domains, which negatively regulates surface-dependent coagulation. Objectives To investigate the influence of FXII truncation on its activation and downstream kallikrein-kinin system activation. Methods We study activation of recombinant FXII variants by chromogenic assays, by FXIIa ELISA and western blotting. Results We demonstrate that FXII truncation primes it for activation by PKa in solution. We demonstrate this phenomenon in three settings. (i) Truncation at a naturally occurring PKa-sensitive cleavage site, R334, accelerates FXIIa formation in solution. A site-directed mutant FXII-R334A displays ~50% reduced activity when exposed to PKa. (ii) A pathogenic mutation in FXII that causes hereditary angioedema, introduces an additional plasmin-sensitive cleavage site. Truncation at this site synergistically accelerates FXII activation in solution. (iii) We identify new, naturally occurring cleavage sites in FXII that have so far not been functionally linked to contact system activation. As examples, we show that non-activating truncation of FXII by neutrophil elastase and cathepsin K primes it for activation by PKa in solution. Conclusions FXII truncation, mediated by either pathogenic mutations or naturally occurring cleavage sites, primes FXII for activation in solution. We propose that the surface-binding domains of FXII shield its activating cleavage site, R353. This may help to explain how the contact system contributes to inflammatory pathology.

The effect of oxygen tension on proteoglycan synthesis and aggregation in mammalian growth plate chondrocytes.

Growth plate chondrocytes isolated from the proliferative and hypertrophic zones of bovine costochondral junctions were grown in vitro in the presence of various oxygen tensions ranging from 3 to 60%. Using [35S] sulfate as an index of glycosaminoglycan synthesis, incorporation was found to be maximal at 21% O2. In contrast, proteoglycan aggregation under the same conditions was found to be maximal at 3% O2. There were no consistent differences in response between cells from the different morphologic zones even though they are exposed to different oxygen tensions in situ. These results show that proteoglycan synthesis and aggregation in growth plate chondrocytes in vitro are differentially affected by the ambient oxygen environment.

Microvessel endothelial cells and pericytes increase proliferation and repress osteoblast phenotypic markers in rat calvarial bone cell cultures.

To investigate the influence of microvessel cells on osteoblasts, we exposed osteoblast-enriched cultures of rat calvarial cells to cultured endothelial cells and pericytes using feeder-layer co-cultures, co-culture dish inserts, and conditioned media experiments. When co-cultured with growth-arrested feeder-layers of endothelial cells or pericytes for 10 days, bone cell cultures showed an increase in cell number and reduction in alkaline phosphatase activity. The response of bone cells to endothelial cells was nearly twice their response to pericytes. A similar response was demonstrated by exposure to microvessel cells in co-culture dish inserts and by exposure to media conditioned by microvessel cells. In long-term cultures of bone cells, the levels of osteocalcin and the number of mineralized nodules both were reduced by exposure to media conditioned by the microvessel cells. Transient exposure to conditioned media from the microvessel cell cultures for 3 days, during the period from initial plating to cell confluence, produced nearly the same effect on the cultures of bone cells as did continuous exposure to these conditioned media. The influence of isolated microvessel cells on osteoblast-enriched calvarial cells was found to be primarily mitogenic, mediated by soluble factors, independent of cell contact, and a cause of prolonged reduction in the expression of early and late markers of the osteoblast phenotype.

Effects of thapsigargin, an intracellular calcium-mobilizing agent, on synthesis and secretion of cartilage collagen and proteoglycan.

The calcium-mobilizing agents thapsigargin and 2,5-di-(tert-butyl)-1,4- benzohydroquinone were shown to markedly elevate the intracellular calcium concentration of chick embryo chondrocytes in a dose-dependent manner. Under these conditions, the metabolism of macromolecules was variably affected. The synthesis and secretion of protein in general, and of collagen in particular, were significantly inhibited; in contrast, proteoglycan synthesis (but not glycosaminoglycan synthesis) was inhibited, whereas secretion was unaffected. Flunarizine, which prevented the thapsigargin-induced intracellular calcium elevation, and EGTA, which caused only a transient thapsigargin-induced intracellular calcium elevation, did not reverse these alterations. It was concluded, therefore, that the observed effects of thapsigargin and 2,5-di-(tert-butyl)-1,4-benzohydroquinone on chondrocyte macromolecule metabolism were not related to the ability of these drugs to increase the cytosolic free calcium concentration but may have been due to the specific depletion of the calcium sequestered in the endoplasmic reticulum. The differential effect of these drugs on protein and proteoglycan secretion suggests that the intracellular trafficking of these two classes of macromolecules may be controlled independently.

Proliferation and macromolecular synthesis by rat calvarial bone cells grown in various oxygen tensions.

Perinatal rat calvarial bone cells were isolated by sequential collagenase digestion and grown in oxygen tensions ranging from 1 to 60% O2. Cell proliferation as determined by automated cell counting and DNA content was greatest in the lower oxygen tensions (less than or equal to 9% O2), whereas alkaline phosphatase activity and [35S]sulfate and [14C]proline incorporation were greatest in the higher oxygen tensions (greater than or equal to 13% O2). It is concluded that lower oxygen concentrations favor bone cell proliferation, whereas higher oxygen concentrations favor macromolecular synthesis. These findings, when related to the known pO2 of the fracture callus, suggest the following sequence of events: first, at the time of fracture an ingrowth of osteoprogenitor cells, capillary buds, and primitive mesenchymal cells occurs in the fracture site, a region of low pO2; second, a great increase in cellular proliferation accompanied by an initiation of macromolecular synthesis follows; finally, as the pO2 levels begin to increase, cellular proliferation decelerates, accompanied by an increase in macromolecular synthesis.

Serum fractions and related agonists with calcium-mobilizing activity in the bovine growth plate chondrocyte.

Longitudinal growth of bone involves a complex sequence of cellular events in the cartilaginous epiphysis. Whole blood serum has been shown previously to be a potent stimulus to the cells of the growth plate, as demonstrated by its ability to activate the inositol phosphate-calcium second messenger system, resulting in a rise in intracellular Ca2+. By manipulating the preparation of serum to functionally separate it into its constituent parts, we have shown that the processes of platelet lysis and activation of the clotting cascade are responsible for the generation of factors that stimulate this signaling mechanism in isolated bovine growth plate chondrocytes. Through a subsequent trial of bioactive agents generated in these processes, we identified and partially characterized several novel agonists of growth plate chondrocytes:adenosine triphosphate and adenosine diphosphate, the purine energy substrates, and bradykinin, the bioactive peptide generated in a side reaction of the clotting cascade, each induces a rise in intracellular Ca2+ via release from intracellular ion stores. Additionally, the three distinct isoforms of platelet-derived growth factor (AA, AB, and BB), also released on platelet lysis, were compared with respect to their ability to stimulate the inositol phosphate-calcium second messenger system in growth plate chondrocytes.

The effect of ascorbic acid on the metabolism of rat calvarial bone cells in vitro.

Addition of 50 micrograms/ml sodium ascorbate to confluent cultures of isolated rat calvarium bone cells resulted in a 21% increase in DNA production, a 50-60% increase in incorporation of [14C]proline into collagenous and noncollagenous proteins, and a 200% increase in alkaline phosphatase activity; under identical conditions, [35S]sulfate incorporation into proteoglycans (glycosaminoglycans) was not affected. These results suggest that ascorbate may be important in maintaining or stimulating the osteogenic phenotype of normal bone cells.

Proliferative and synthetic response of bovine growth plate chondrocytes to various capacitively coupled electrical fields.

In vitro monolayer cultures of growth plate chondrocytes isolated from newborn calf costochondral junctions were subjected to capacitively coupled electrical fields for 48 h. In part A, the electrical signal was a 60-kHz sine wave applied at different voltages so as to produce electrical fields at the pericellular level of 7, 20, 50, and 126 mV/cm. Incorporations of [3H]thymidine and [35S]sulfate were assayed to determine the effect of the above fields on cells proliferation and matrix synthesis, respectively. Proliferation was increased by 47% in the 20 mV/cm field whereas the same field decreased [35S]sulfate incorporation by 21%. These changes were significant at p less than 0.05 in both instances. In part B, the 20 mV/cm field was applied in a pulsed fashion to produce daily duty cycles of 100, 25, 2, and 0.25%. Incorporation of [3H]thymidine, [35S]sulfate, and [14C]proline per DNA were assayed. Results indicated that the 100, 25, and 0.25% percent duty cycles showed significantly (p less than 0.01-0.05) increased proliferation, whereas the 0.25% signal (5 ms on/495 ms off for 6 h/day) significantly decreased [14C]proline incorporation. We conclude that the biologic response of cells in vitro is signal specific, and that the total amount of electrical energy required to stimulate the growth plate chondrocyte to increased proliferation is very small since the total time the 0.25% duty cycle signal was only 3.6 min of a 24-h period.

Surface distribution of flash-evoked and pattern reversal-evoked potentials in hooded rats.

Simultaneous recording from 21 electrode sites in a 4 X 4 mm area over the posterior cortex was used to determine the surface distribution of all major peaks which constitute flash-evoked potentials (FEPs) and pattern reversal evoked-potentials (PREPs) in hooded rats. Topographical maps were constructed with respect to Bregma and midline reference points. The data indicate that not all of the peaks which constitute either evoked potential have their greatest amplitude within the classically defined primary visual cortex. Further, since the FEPs were produced by uniform stimulation, the data suggest that surface regions of the rat visual cortex differ in ways other than simply the portion of the visual field from which information is received.

Effects of client interviewers on client-reported satisfaction with mental health services.

A study at two outpatient facilities compared two methods of collecting data on client satisfaction with mental health services provided by case managers and by physicians. A satisfaction survey instrument was developed with input from clients. A total of 120 clients were randomly assigned to be interviewed by either a staff member or a client. Clients from both facilities reported high levels of satisfaction regardless of the type of interviewer. Clients gave a significantly greater number of extremely negative responses when they were interviewed by client interviewers. No difference between the two groups was found in overall satisfaction with services received from case managers or physicians.

Helmet use, patterns of injury, medical outcome, and costs among motorcycle drivers in Maryland.

A comprehensive study was conducted of all motorcycle traffic crashes occurring in Maryland during a one-year period. All available medical and cost data were linked with police crash reports. During the study period, 1,900 motorcycle drivers were involved in crashes. The data indicated that (i) helmet usage was 35% overall, 30% among fatally injured drivers, and only 16% among drivers with a history of drug/alcohol conviction, (ii) unhelmeted drivers seen at an emergency department were almost twice as likely to have sustained head injury (40%) as were helmeted drivers (21%) (the corresponding percentages for hospitalized drivers were 55% and 38%), and (iii) acute care cost for unhelmeted drivers was three times ($30,365) that of helmeted drivers.

Proteoglycan synthesis and content in articular cartilage and cartilage repair tissue in horses.

Hexosamine concentration, DNA concentration, and [35S]sulfate incorporation for articular cartilage obtained from various sites in the metacarpophalangeal and carpal joints of horses were measured. The same measurements were made on the repair tissue filling full-thickness articular defects in the intermediate carpal bone and on cartilage surrounding partial-thickness defects 6 weeks after the defects were created arthroscopically. Cellularity (measured as DNA concentration), proteoglycan content (measured as hexosamine concentration), and proteoglycan synthesis (measured as [35S]sulfate incorporation) varied according to the site sampled. Cartilage from the transverse ridge of the head of the third metacarpal bone and the radial facet of the third carpal bone had the lowest hexosamine concentration, whereas rate of proteoglycan synthesis was lowest in cartilage from the transverse ridge of the head of the third metacarpal bone and the distal articular surface of the radial carpal bone. Repair tissue filling a full-thickness cartilage defect at 6 weeks was highly cellular. It was low in proteoglycan content, but was actively synthesizing these macromolecules. In contrast, the cartilage surrounding a partial-thickness defect was unchanged 6 weeks after the original defect was made.