Sleep disturbance underlies the co-occurrence of trauma and pediatric chronic pain: a longitudinal examination.
Epidemiological and cross-sectional studies have shown that post-traumatic stress disorder symptoms (PTSS) are common and impairing in youth with chronic pain. Yet, the co-occurrence of PTSS and pediatric chronic pain has not been examined longitudinally, which has limited understanding of theoretically proposed mechanisms (eg, sleep disturbance) underlying the PTSS-pain relationship over time. This longitudinal study aimed to fill this gap. Participants included 138 youth (Mage = 14.29, 75% girls) referred to a tertiary-level outpatient chronic pain program and one of their parents. At baseline, youth reported their pain intensity and interference, PTSS, and subjective sleep disturbances (ie, sleep quality and insomnia). Youth and parents completed semistructured diagnostic interviews to determine the child's post-traumatic stress disorder diagnostic status, and youth completed an objective assessment of sleep patterns for 7 days using actigraphy. At 3-month follow-up, youth once again completed the diagnostic interview and reported their pain intensity, pain interference, and PTSS. Partially latent cross-lagged structural equation panel models revealed that, controlling for pain intensity, pain interference and PTSS co-occurred at baseline, but not at follow-up (while controlling for baseline levels). Higher levels of baseline PTSS were predictive of increases in pain interference at follow-up. Furthermore, subjective sleep disturbances mediated the relationship between baseline PTSS and follow-up pain interference. These findings lend support to conceptual models of PTSS-pain co-occurrence and highlight a critical need to assess and address trauma and sleep disturbances in youth with chronic pain.


Phacoemulsification in a clouded leopard (Neofelis nebulosa).
Phacoemulsification and prophylactic retinopexy were performed on a 3-month-old hand-raised clouded leopard with a unilateral mature cataract. The same procedures were repeated 3 months later when a cataract developed in the fellow eye. Examination procedures, anesthetic protocols, and surgical techniques were similar to those utilized in domestic cats. The patient retains highly functional aphakic vision at the present age of 2.5 years. An inherited basis for the cataracts is proposed. Although the cub was hand raised, the cataracts were unlike nutritional cataracts reported previously in domestic cats and dogs. To the author's knowledge this is the first report of cataract formation and phacoemulsification in a clouded leopard.


cJUN N-terminal kinase (JNK) activation mediates islet amyloid-induced beta cell apoptosis in cultured human islet amyloid polypeptide transgenic mouse islets.
Aggregation of human islet amyloid polypeptide (hIAPP) as islet amyloid is associated with increased beta cell apoptosis and reduced beta cell mass in type 2 diabetes. Islet amyloid formation induces oxidative stress, which contributes to beta cell apoptosis. The cJUN N-terminal kinase (JNK) pathway is a critical mediator of beta cell apoptosis in response to stress stimuli including oxidative stress and exogenous application of hIAPP. We determined whether amyloid formation by endogenous hIAPP mediates beta cell apoptosis through JNK activation and downstream signalling pathways. hIAPP transgenic and non-transgenic mouse islets were cultured for up to 144 h in 16.7 mmol/l glucose to induce islet amyloid in the presence or absence of the amyloid inhibitor Congo Red or a cell-permeable JNK inhibitor. Amyloid, beta cell apoptosis, JNK signalling and activation of downstream targets in the intrinsic and extrinsic apoptotic pathways were measured. JNK activation occurred with islet amyloid formation in hIAPP transgenic islets after 48 and 144 h in culture. Neither high glucose nor the hIAPP transgene alone was sufficient to activate JNK independent of islet amyloid. Inhibition of islet amyloid formation with Congo Red reduced beta cell apoptosis and partially decreased JNK activation. JNK inhibitor treatment reduced beta cell apoptosis without affecting islet amyloid. Islet amyloid increased mRNA levels of markers of the extrinsic (Fas, Fadd) and intrinsic (Bim [also known as Bcl2l11]) apoptotic pathways, caspase 3 and the anti-apoptotic molecule Bclxl (also known as Bcl2l1) in a JNK-dependent manner. Islet amyloid formation induces JNK activation, which upregulates predominantly pro-apoptotic signals in both extrinsic and intrinsic pathways, resulting in beta cell apoptosis.


Myeloid-derived suppressor cells impair the quality of dendritic cell vaccines.
Myeloid-derived suppressor cells (MDSC) are important regulators of the immune system and key players in tumor-induced suppression of T-cell responses. CD14+HLA-DR-/low MDSC have been detected in a great number of malignancies, including melanoma. MDSC are known to be impaired in their ability to differentiate along the myeloid lineage, e.g., into dendritic cells (DC). This is a concern for utilization of monocyte-derived DC for vaccination of patients with melanoma or other cancers exhibiting accumulation of CD14+ MDSC. When producing DC according to standard operating procedures of two currently ongoing clinical trials, we found that MDSC co-purified with monocytes isolated by elutriation. MDSC frequencies did not affect yield or viability of the produced DC, but induced a dose-dependent decrease in DC maturation, ability to take up antigen, migrate and induce T-cell IFNγ production. Changes in DC characteristics were most notable when 'pathological' frequencies of >50% CD14+HLA-DR- cells were present in the starting culture. The impaired DC quality could not be explained by altered cytokine production or increased oxidative stress in the cultures. Tracking of HLA-DR- cells throughout the culture period revealed that the observed changes were partially due to the impaired maturation and functionality of the originally HLA-DR- population, but also to their negative effects on HLA-DR+ cells. In conclusion, MDSC could be induced to differentiate into DC but, due to the impairment of overall DC vaccine quality when >50% HLA-DR- cells were present in the starting culture, their removal could be advisable.


Bacterial translocation: overview of mechanisms and clinical impact.
Bacterial translocation (BT) is a phenomenon in which live bacteria or its products cross the intestinal barrier. Gut translocation of bacteria has been shown in both animal and human studies. BT and its complications have been shown clearly to occur in animal models, but its existence and importance in humans has been difficult to ascertain. We review the mechanisms of BT and its clinical impact based on the current literature.


Plating of Proximal Ulna Fractures Using Posterolateral Distal Humerus Plates: Surgical Technique and Case Series.
Precontoured olecranon plates are frequently used in the management of proximal ulna fractures. Occasionally, in comminuted proximal ulna fractures or segmental ulna fractures, available precontoured olecranon plates are too short for the management of these fractures. The authors have utilized posterolateral distal humerus plates in these instances. The coronal bend in some posterolateral distal humerus plates anecdotally fits well to the proximal ulna, despite being designed for the distal humerus. We sought to measure the coronal angulation of precontoured posterolateral distal humerus plates from various companies and compare these to established proximal ulna angles. Case examples are also provided.


Epilepsy Surgery in Extratemporal vs Temporal Lobe Epilepsy: Changes in Surgical Volumes and Seizure Outcome Between 1990 and 2017.
Seizure outcome after extratemporal lobe epilepsy (exTLE) surgery has often been poorer than after temporal lobe epilepsy (TLE) surgery, but recent improvements in diagnostics and surgery may have changed this. Our aim was to analyze the changes in presurgical and surgical volumes and seizure outcome 2 years after surgery for patients with exTLE compared with those with TLE. We performed a retrospective, single-center cohort study including patients from the Bethel presurgical-surgical-postsurgical database from 1990 to 2017. We used logistic regression to analyze factors influencing the odds for surgery and the odds for seizure freedom after surgery. We included 3,822 patients with presurgical evaluation, 2,404 of whom had subsequently undergone surgery. The proportion of patients with exTLE in presurgical evaluation increased from 41% between 1990 and 1993 to 64% in 2014-2017. The odds for surgery decreased over time (2003-2011: odds ratio [OR] 0.50 [95% CI 0.36-0.70]; 2012-2017: OR 0.24 [CI 0.17-0.35]; reference: 1990-2002) and patients with exTLE had lower odds for surgery than patients with TLE, but this difference diminished over time (exTLE vs TLE 1990-2002: OR 0.14 [CI 0.09-0.20]; 2003-2011: OR 0.32 [CI 0.24-0.44]; 2012-2017: OR 0.46 [CI 0.34-0.63]). Etiology, the side of the epileptogenic lesion, and invasive recordings influenced the odds for surgery. The most frequent reasons for not undergoing surgery were missing identification of a circumscribed epileptogenic zone or an unacceptable risk of postsurgical deficits in patients with exTLE and the patient's decision in patients with TLE. Compared with patients with TLE, the odds for seizure freedom after surgery started lower for patients with exTLE in earlier years, but increased (≤2 lobes 1990-2002: OR 0.47 [CI 0.33-0.68]; 2003-2011: OR 0.62 [CI 0.44-0.87]; 2012-2017: OR 0.78 [CI 0.53-1.15]; ≥3 lobes 1990-2002: OR 0.37 [CI 0.22-0.62]; 2003-2011: OR 0.73 [CI 0.43-1.23]; 2012-2017: OR 1.46 [CI 0.91-2.42]). Etiology, age at surgery, and invasive recordings were further predictors for the odds for seizure freedom. Over the past 28 years, the success of resective surgery for patients with exTLE has improved. At the same time, the number of patients with exTLE being evaluated for surgery increased, as well as their odds for undergoing surgery.


[The protective effect of dachuanxiongwan on the rats with focal cerebral ischemia and reperfusion].
Studying the protective effect of dachuanxiongwan (DCXW) on the rats with focal cerebral ischemia and reperfusion. The ischemia and reperfusion model was established by blocking the rat's middle cerebral artery with a pre-set nylon thread and removing it from the internal carotid artery 2 hours after occlusion. 20 healthy male Sprague-Dawley rats following middle cerebral artery occlusion (MCAO) were randomly divided into two groups: Group A, transient ischemia, for control; Group B, transient ischemia treated with DCXW via gavage, 4.13 g/kg x d, twice a day for 3 days, while group A being given the same volume of saline. Seventy-two hours after reperfusion, the neurological function of all rats was evaluated according to Longa, and the rats were sacrificed. All the samples of cerebrum were processed and embedded in paraffin and cut into sections. The sections were stained with Hematoxylin & Eosin to measure the infarction volume and evaluate the effects of DCXW. The grade of neurological function of the treatment group (1.5+/-0.71) was lower than that of the control group (2.3+/-0.82), there was a statistically significant difference between the two groups (P=0.032); the infarction volume of the treatment group was smaller than that of the control group, there was a statistically significant difference between the two groups (P=0.000). The findings suggest that DCXW has a protective effect on the cerebrum undergoing ischemia and reperfusion.


Seedling Biometry of nud Knockout and win1 Knockout Barley Lines under Ionizing Radiation.
The genes NUD and WIN1 play a regulatory role in cuticle organization in barley. A knockout (KO) of each gene may alter plant mechanisms of adaptation to adverse environmental conditions. A putative pleiotropic effect of NUD or WIN1 gene mutations in barley can be assessed in a series of experiments in the presence or absence of a provoking factor. Ionizing radiation is widely used in research as a provoking factor for quantifying adaptive potential of living organisms. Our aim was to evaluate initial stages of growth and development of barley lines with a KO of NUD or WIN1 under radiation stress. Air-dried barley grains with different KOs and wild-type control (WT) were exposed to γ-radiation at 50, 100, or 200 Gy at a dose rate of 0.74 R/min. Approximately 30 physiological parameters were evaluated, combined into groups: (1) viability, (2) radiosensitivity, and (3) mutability of barley seed progeny. Seed germination, seedling survival, and shoot length were similar among all barley lines. Naked nud KO lines showed lower weights of seeds, roots, and seedlings and shorter root length as compared to win1 KO lines. The shoot-to-root length ratio of nud KO lines' seedlings exceeded that of win1 KO and WT lines. In terms of the number of seedlings with leaves, all the KO lines were more sensitive to pre-sowing γ-irradiation. Meanwhile, the radioresistance of nud KO lines (50% growth reduction dose [RD50] = 318-356 Gy) and WT plants (RD50 = 414 Gy) judging by seedling weight was higher than that of win1 KO lines (RD50 = 201-300 Gy). Resistance of nud KO lines to radiation was also demonstrated by means of root length (RD50 = 202-254 Gy) and the shoot-to-root length ratio. WT seedlings had the fewest morphological anomalies. In nud KO lines, mainly alterations of root shape were found, whereas in win1 KO lines, changes in the color and shape of leaves were noted. Thus, seedlings of nud KO lines are characterized mainly by changes in the root system (root length, root number, and root anomalies). For win1 KO lines, other parameters are sensitive (shoot length and alterations of leaf shape and color). These data may indicate a pleiotropic effect of genes NUD and WIN1 in barley.


Oral Fosfomycin for the Treatment of Acute and Chronic Bacterial Prostatitis Caused by Multidrug-Resistant Escherichia coli.
Acute and chronic bacterial prostatitis in outpatients is commonly treated with oral fluoroquinolones; however, the worldwide dissemination of multidrug-resistant (MDR) Escherichia coli has resulted in therapeutic failures with fluoroquinolones. We reviewed the literature regarding the use of oral fosfomycin in the treatment of acute and chronic prostatitis caused by MDR E. coli. All English-language references on PubMed from 1986 to June 2017, inclusive, were reviewed from the search "fosfomycin prostatitis." Fosfomycin demonstrates potent in vitro activity against a variety of antimicrobial-resistant E. coli genotypes/phenotypes including ciprofloxacin-resistant, trimethoprim-sulfamethoxazole-resistant, extended-spectrum β-lactamase- (ESBL-) producing, and MDR isolates. Fosfomycin attains therapeutic concentrations (≥4 μg/g) in uninflamed prostatic tissue and maintains a high prostate/plasma ratio up to 17 hours after oral administration. Oral fosfomycin's clinical cure rates in the treatment of bacterial prostatitis caused by antimicrobial-resistant E. coli ranged from 50 to 77% with microbiological eradication rates of >50%. An oral regimen of fosfomycin tromethamine of 3 g·q 24 h for one week followed by 3 g·q 48 h for a total treatment duration of 6-12 weeks appeared to be effective. Oral fosfomycin may represent an efficacious and safe treatment for acute and chronic prostatitis caused by MDR E. coli.


The parenteral kinetics of ampicillin/sulbactam in man.
The kinetics of co-administered ampicillin plus sulbactam were examined at doses being used in clinical trials of this combination of a beta-lactam antibiotic (ampicillin) and a beta-lactamase inhibitor (sulbactam). Following 15-min infusion of 2 g ampicillin plus 1 g sulbactam, peak serum concentrations of 120 micrograms/ml ampicillin and 60 micrograms/ml sulbactam were observed. The half-life was approximately one hour for both drugs. Approximately 75% of the dose of sulbactam and ampicillin was recovered in urine. The data fit a two-compartment pharmacokinetic model. Intramuscular administration of 1 g ampicillin plus 0.5 g sulbactam produced mean peak concentrations of 18 micrograms/ml ampicillin plus 13 micrograms/ml sulbactam. Estimates of variability of the data in normal male subjects are provided to serve as references for clinical trials.


A Low-Cost Partner Notification Strategy for the Control of Sexually Transmitted Diseases: A Case Study From Louisiana.
We estimated the costs and effectiveness of implementing a partner notification (PN) strategy for highly prevalent sexually transmitted diseases (STDs) within the Louisiana STD/HIV Program. We carried out a telephone-based PN approach on an experimental basis in 2 public STD clinics in Louisiana from June 2010 to May 2012. We monitored data on the resources used for identifying, tracing, treating, and managing the infected cases and their partners to estimate the intervention costs. Our results indicated that implementation of telephone-based PN should not increase the STD control program's expenses by more than 4.5%. This low-cost PN approach could successfully identify and treat 1 additional infected case at a cost of only $171. We found that the cost per disability-adjusted life year averted (a health outcome measure), because of the adoption of selective screening with partner tracing, was $4499. This was significantly lower than the gross domestic product per capita of the United States, a threshold used for defining highly cost-effective health interventions. Adoption of PN for gonorrhea and chlamydia should be considered a national strategy for prevention and control of these diseases.


Antiplasmodial activity of Cryptolepis sanguinolenta alkaloids from leaves and roots.
The roots of Cryptolepis sanguinolenta have been investigated for their chemical composition since 1931 but so far no studies on the leaves have been reported although they are used in traditional medicine in Guinea-Bissau. Two new alkaloids identified as cryptolepinoic acid (1) and methyl cryptolepinoate (2) and the known alkaloids cryptolepine (4), hydroxycryptolepine (5/5a) and quindoline (6), were isolated from the ethanolic and chlorophormic leaf extracts. Aqueous and ethanolic extracts of the leaves and roots and seven alkaloids isolated from those extracts were tested in vitro against Plasmodium falciparum K1 (multidrug-resistant strain) and T996 (chloroquine-sensitive clone). All the extracts were shown to give 90% inhibition of P. falciparum K1 growth at concentrations < 23 micrograms/ml. Cryptolepine (4) was the most active alkaloid tested with IC50 values (0.23 microM to K1; 0.059 microM to T996) comparable with chloroquine (0.26 microM to K1; 0.019 microM to T996). The indolobenzazepine alkaloid cryptoheptine (7) was the second most active with IC50 values of 0.8 microM (K1) and 1.2 microM (T996). Cryptolepinoic acid (1) showed no significant activity while its ethyl ester derivative 3 was active against P. falciparum K1 (IC50 = 3.7 microM). All the indoloquinoline alkaloids showed cross-resistance with chloroquine but not the indolobenzazepine alkaloid 7. It was noticed that alkaloids with weakly basic characteristics were active whereas other structurally related alkaloids with different acid-base profiles were inactive. These observations are in agreement with the antimalarial mechanism of action for quinolines.


Expression and activity of cell-wall-degrading enzymes in the latex of opium poppy, Papaver somniferum L.
The alkaloid-rich latex of the opium poppy, Papaver somniferum L., is valued as a source of pharmaceuticals including thebaine, codeine, and morphine, but is also harvested for heroin production. The poppy laticifer system develops through the gradual disappearance of the common walls between differentiating laticifer elements throughout the plant. Gene homologues for cell-wall-degrading enzymes were found during random sequencing of an opium poppy latex cDNA library. RNA gel blot analysis of cellulase, polygalacturonase beta-subunit, 1,3-beta-glucanase, and xyloglucan endotransglycosylase homologues showed their expression was not limited to laticifers. In contrast, poppy gene homologues to pectin methylesterase (PME), pectin acetylesterase (PAE) and pectate lyase (PL) where all highly expressed and latex-specific. Enzyme assays confirmed the presence of PME, PAE, and PL activities in latex serum. The abundance of transcripts encoding pectin-degrading enzymes in latex suggests that these enzymes may play an important role in laticifer development.


[Effects of butylphthalide on bronchial asthma in guinea pigs and involvement of endothelin].
To study the effects of butylphthalide on bronchial asthma in guinea pigs, and investigate the involvement of endothelin. In guinea pigs, bronchial asthma was induced by injection of ovalbumin (OVA) and provoked by inhalation of OVA, and the effects of butylphthalide on asthma were evaluated through the changes it induced by OVA, pulmonary function, endothelin-1 (ET-1) contents and activity of endothelin converting enzyme-1 (ECE-1) in bronchoalveolar lavage fluid (BALF), serum and lung tissue, and the gene expression of ET-1 in lung tissue. Butylphthalide significantly improved pulmonary function, lowered asthmatic behavior score, inhibited the activity of ECE-1, and reduced ET-1 gene expression level in lung tissue. Butylphthalide has an anti-asthma effect and the mechanisms involve inhibition of ECE-1 activity and lowering of ET-1geng expression.


Therapeutic utilities of fibroblast growth factor 19.
Diabetes and associated metabolic conditions have reached pandemic proportions worldwide and there is a clear unmet medical need for new therapies that are both effective and safe. FGF19 is a distinctive member of the FGF family that functions as an endocrine hormone. An up-to-date report on the exciting findings related to the involvement of FGF19 in the regulation of glucose, bile acid metabolism and energy expenditure. The role of FGF receptors in these different activities. The therapeutic potential of FGF19 and the engineering opportunities for removing undesirable mitogenic activity. The ability of FGF19 to regulate bile acid homeostasis, gallbladder filling and tumor development and its potent ability to normalize glucose, lipid and energy homeostasis have made it a potential therapeutic target for the treatment of patients with gallstones, cancer and metabolic diseases, among others. Its potential utility as a novel therapeutic for both type 1 and type 2 diabetes is of particular interest. The ability to separate the undesired mitogenic activity from its potent metabolic activities has opened new opportunities for the development of potential therapeutic molecules based on FGF19 in treating various conditions associated with metabolic syndrome.


Bleeding increases the risk of ischemic events in patients with peripheral arterial disease.
Patients with peripheral arterial disease are at high risk of ischemic events and therefore are treated with antithrombotics. In patients with coronary artery disease or cerebrovascular disease, bleeding is related to the subsequent occurrence of ischemic events. Our objective was to assess whether this is also the case in patients with peripheral arterial disease. All patients from the Dutch Bypass and Oral Anticoagulants or Aspirin (BOA) Study, a multicenter randomized trial comparing oral anticoagulants with aspirin after infrainguinal bypass surgery, were included. The primary outcome event was the composite of nonfatal myocardial infarction, nonfatal ischemic stroke, major amputation, and cardiovascular death. To identify major bleeding as an independent predictor for ischemic events, crude and adjusted hazard ratios with 95% confidence intervals were calculated with multivariable Cox regression models. From 1995 until 1998, 2650 patients were included with 101 nonfatal major bleedings. During a mean follow-up of 14 months, the primary outcome event occurred in 218 patients; 22 events were preceded by a major bleeding. The mean time between major bleeding and the primary outcome event was 4 months. Major bleeding was associated with a 3-fold increased risk of subsequent ischemic events (crude hazard ratio, 3.0; 95% confidence interval, 1.9 to 4.6; adjusted hazard ratio, 3.0; 95% confidence interval, 1.9 to 4.7). In patients with peripheral arterial disease, as in patients with coronary artery disease or cerebrovascular disease, major bleeding was independently associated with major ischemic complications. Without compromising the benefits of antithrombotics, these findings call for caution relative to the risks of major bleeding.


Volvulus of the caecum. An evaluation of various surgical procedures.
To evaluate the various operations for caecal volvulus we reviewed 48 patients who were treated between 1948 and 1989. Six were treated conservatively (the volvulus resolved before operation), and the remaining 42 patients (43 operations) were treated by untwisting (n = 14, 2 early deaths); caecopexy (n = 13, no deaths); caecostomy (n = 3, 2 early deaths); or resection (n = 13, one early death). At follow up a mean of 11.8 years later (range 0.4 to 34) the numbers of patients who had remained free of symptoms were 6, 5, 1 and 9, respectively. We conclude that resection gives the best long term results with acceptable mortality and morbidity and should be the treatment of choice for caecal volvulus.


[Effect of attenuation correction and scatter compensation on the 99mTc-MIBI myocardial perfusion spect in patients without coronary artery disease].
Attenuation correction (AC) and scatter compensation (SC) techniques are recent developments of myocardial perfusion SPECT. Our aim was to evaluate the effect of AC + SC on the myocardial distribution of 99mTc-MIBI in a population without coronary artery disease. A multiarray of Gd-153 linear sources was used for simultaneous transmission/emission 99mTc-MIBI myocardial perfusion SPECT in 27 patients without coronary artery disease. A visual analysis and polar map quantification was performed. Changes between non-corrected (NC) and corrected (AC + SC) studies were compared. AC + SC produced an increase in liver activity and better visualization of the right ventricle. Intestinal activity increased in six patients. Myocardial homogeneity was increased by AC + SC. No differences by gender were observed after AC + SC. In females AC + SC led to a decrease of uptake in the anterior wall, apex and apical segments of the lateral wall and septum, and an increase in the inferior wall. In males AC + SC caused an increase of uptake in the inferior wall and in the basal segments of septum and a decrease of uptake in apex and apical segments of anterior and lateral walls. AC + SC generated false defects in the anterior wall of five patients. Our results show the usefulness of AC + SC for compensating the interferences produced by attenuation on the myocardial distribution of 99mTc-MIBI. Because AC + SC may introduce false defects, it must not be applied to normal perfused myocardium.


Phosphoenolpyruvate carboxylase of Escherichia coli. Hydrophobic chromatography using specific elution with allosteric inhibitor.
The adsorption of Escherichia coli phosphoenolpyruvate carboxylase [EC 126.96.36.199] to butyl-, hexyl-, and octyl-Sepharose gels was investigated. The enzyme was nearly completely adsorbed to the latter two gels both in the absence and presence of high concentrations of ammonium sulfate. At intermediate concentrations--0.1 M in the case of hexyl-Sepharose--virtually no adsorption was observed. Upon application of an increasing or decreasing concentration gradient of the salt, the enzyme was eluted at various concentrations of the salt depending on chain length of the immobilized alkyl groups. The adsorption to hexyl-Sepharose at 0.7 M ammonium sulfate was markedly decreased by L-aspartate, the allosteric inhibitor, whereas it was increased by acetyl-CoA, one of the allosteric activators. Evidence was obtained suggesting that these changes in adsorption were due to conformational alterations of the enzyme elicited by these effectors. The enzyme seemed to have been adsorbed at its hydrophobic regions which were distinct from the allosteric site for long-chain fatty acids. The specific elution with L-aspartate in the presence of 0.82 M ammonium sulfate could successfully be applied to purification of the enzyme. By this hydrophobic interaction chromatography, the enzyme was purified about 55-fold over its partially purified preparation with a recovery of 73%. The obtained enzyme preparation was almost homogeneous as judged from sodium dodecylsulfate-polyacrylamide gel electrophoresis.


Design and Experimental Research of Knee Joint Prosthesis Based on Gait Acquisition Technology.
Whether the lower limb prosthesis can better meet the needs of amputees, the biomimetic performance of the knee joint is particularly important. In this paper, Nokov(metric) optical 3D motion capture system was used to collect motion data of normal human lower limbs, and the motion instantaneous center of multi-gait knee joint was obtained. Taking the error of knee joint motion instantaneous center line as the objective function, a set of six-bar mechanism prosthetic knee joint was designed based on a genetic algorithm. The experimental results show that the movement trajectory of the instantaneous center of the knee joint is basically similar to that of the human knee joint, so it can help amputees complete a variety of gaits and has good biomimetic performance. Gait acquisition technology can provide important data for prosthetic designers and it will be widely used in prosthetic design and other fields.


Magnitude and kinetics of alterations in plasma catecholamines and leukocyte beta-adrenergic receptors in response to anaesthesia and surgery.
We studied the response of the sympatho-adrenal system to varying intensities of different stimuli. Concentrations of norepinephrine and epinephrine in plasma as well as densities of beta 2-adrenergic receptors on mononuclear leukocytes were determined in patients subjected to operations of varying complexity and different types of anaesthesia. In patients undergoing hysterectomy (n = 9), the maximal increases in plasma norepinephrine and epinephrine were 2.7- and 2.8-fold, respectively, corresponding to a post-operative decrease of the mononuclear leukocyte beta 2-adrenergic receptors of 27% after 4 hours. Patients with coronary revascularization (n = 17) were randomly selected to receive either enflurane/N2O or neurolept anaesthesia. During intraoperative periods of stress, such as cardiopulmonary bypass and hypothermia, norepinephrine and epinephrine levels were 2-3 times higher in the neurolept patients, compared with the enflurane patients. In the former group, the respective maximal norepinephrine and epinephrine concentrations were 9.7 and 28 times the vasal values of the non-anaesthetized patients. One day postoperatively, the mononuclear leukocyte beta 2-receptor density decreased maximally by 45 +/- 11% in the enflurane patients, and by 53 +/- 6% in the neurolept patients. As early as two to five days after cardiac surgery, beta 2-receptor densities were no longer distinguishable from the preoperative values. Significant correlations between the increases in catecholamine concentrations and the decreases in beta 2-receptor densities did not exist. It is concluded that enflurane blocks the sympatho-adrenal response to surgical stress more effectively than neurolept anaesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)


meso-Alkylidene (m-benzi)pentaphyrin: a modified pentaphyrin bearing exocyclic double bonds at meso-positions.
meso-Alkylidene (m-benzi)pentaphyrin containing exocyclic C=C double bonds at two meso-positions is synthesized and fully characterized for the first time. The single crystal X-ray crystallographic analysis shows a concave conformation with two pyrrole rings inverted. The first protonation occurs exclusively at core nitrogen. The synthesized compound displays concentration dependent chromogenic responses for fluoride anion in organic solvent.


Mood symptoms contribute to working memory decrement in active-duty soldiers being treated for posttraumatic stress disorder.
A significant proportion of military veterans of operations in Afghanistan and Iraq have been diagnosed with posttraumatic stress disorder (PTSD). Growing evidence suggests that neuropsychological deficits are a symptom of PTSD. The current study investigated neurocognitive functioning among soldiers diagnosed with PTSD. Specifically, active-duty soldiers with and without a diagnosis of PTSD were assessed for performance on tests of attention and working memory. In addition, factors such as combat experience, depression, anxiety, PTSD symptom severity, and alcohol consumption were explored as possible mediators of group differences in neurocognitive functioning. Twenty-three active-duty soldiers diagnosed with PTSD were matched with 23 healthy Soldier controls; all were administered the Attention Network Task (ANT), Backward Digit Span (BDS) task, Beck Depression Inventory, Beck Anxiety Inventory, PTSD Checklist-Military Version, Combat Exposure Scale, and Modified Drinking Behavior Questionnaire. Soldiers diagnosed with PTSD performed significantly worse on the working memory task (BDS) than healthy controls, and reported greater levels of PTSD symptoms, combat exposure, depression, and anxiety. However, after controlling for depression and anxiety symptoms, the relationship between PTSD and working memory was no longer present. The results indicate that PTSD is accompanied by deficits in working memory, which appear to be partially attributed to anxiety and depression symptoms.


Asynchronous Event-Based Fourier Analysis.
This paper introduces a method to compute the FFT of a visual scene at a high temporal precision of around 1- [Formula: see text] output from an asynchronous event-based camera. Event-based cameras allow to go beyond the widespread and ingrained belief that acquiring series of images at some rate is a good way to capture visual motion. Each pixel adapts its own sampling rate to the visual input it receives and defines the timing of its own sampling points in response to its visual input by reacting to changes of the amount of incident light. As a consequence, the sampling process is no longer governed by a fixed timing source but by the signal to be sampled itself, or more precisely by the variations of the signal in the amplitude domain. Event-based cameras acquisition paradigm allows to go beyond the current conventional method to compute the FFT. The event-driven FFT algorithm relies on a heuristic methodology designed to operate directly on incoming gray level events to update incrementally the FFT while reducing both computation and data load. We show that for reasonable levels of approximations at equivalent frame rates beyond the millisecond, the method performs faster and more efficiently than conventional image acquisition. Several experiments are carried out on indoor and outdoor scenes where both conventional and event-driven FFT computation is shown and compared.


Using Data to Improve the Management of Diabetes: The Tayside Experience.
Tayside is a region in the East of Scotland and forms one of nine local government regions in the country. It is home to approximately 416,000 individuals who fall under the National Health Service (NHS) Tayside health board, which provides health care services to the population. In Tayside, Scotland, a comprehensive informatics network for diabetes care and research has been established for over 25 years. This has expanded more recently to a comprehensive Scotland-wide clinical care system, Scottish Care Information - Diabetes (SCI-Diabetes). This has enabled improved diabetes screening and integrated management of diabetic retinopathy, neuropathy, nephropathy, cardiovascular health, and other comorbidities. The regional health informatics network links all of these specialized services with comprehensive laboratory testing, prescribing records, general practitioner records, and hospitalization records. Not only do patients benefit from the seamless interconnectedness of these data, but also the Tayside bioresource has enabled considerable research opportunities and the creation of biobanks. In this article we describe how health informatics has been used to improve care of people with diabetes in Tayside and Scotland and, through anonymized data linkage, our understanding of the phenotypic and genotypic etiology of diabetes and associated complications and comorbidities.


Primary cardiac hydatid disease: cross-sectional imaging features.
Although hydatid disease is common, individual series are usually not large as far as primary cardiac hydatid disease is concerned. We believe this study is the largest series of primary cardiac hydatid disease for which cross-sectional imaging is available. Methods. We reviewed the radiologic and medical records of 9 pathologically proven cases of primary cardiac hydatid disease. Echocardiography, computed tomography (CT), and magnetic resonance imaging (MRI) were used. In 5 patients, all three modalities were used, and in 4 only CT was available. Three types of cardiac involvement (pericardial, left ventricular, and right atrial wall) were detected. The cysts showed daughter cyst formation, detached parasitic membrane, rupture, segmental calcification, and end-stage calcification. Echocardiography is useful in detecting the cystic nature. Computed tomography best shows the wall calcification. Magnetic resonance imaging depicts the exact anatomic location and nature of the internal and external structures and is the modality of posttreatment follow-up.


Rise of dinosaurs reveals major body-size transitions are driven by passive processes of trait evolution.
A major macroevolutionary question concerns how long-term patterns of body-size evolution are underpinned by smaller scale processes along lineages. One outstanding long-term transition is the replacement of basal therapsids (stem-group mammals) by archosauromorphs, including dinosaurs, as the dominant large-bodied terrestrial fauna during the Triassic (approx. 252-201 million years ago). This landmark event preceded more than 150 million years of archosauromorph dominance. We analyse a new body-size dataset of more than 400 therapsid and archosauromorph species spanning the Late Permian-Middle Jurassic. Maximum-likelihood analyses indicate that Cope's rule (an active within-lineage trend of body-size increase) is extremely rare, despite conspicuous patterns of body-size turnover, and contrary to proposals that Cope's rule is central to vertebrate evolution. Instead, passive processes predominate in taxonomically and ecomorphologically more inclusive clades, with stasis common in less inclusive clades. Body-size limits are clade-dependent, suggesting intrinsic, biological factors are more important than the external environment. This clade-dependence is exemplified by maximum size of Middle-early Late Triassic archosauromorph predators exceeding that of contemporary herbivores, breaking a widely-accepted 'rule' that herbivore maximum size greatly exceeds carnivore maximum size. Archosauromorph and dinosaur dominance occurred via opportunistic replacement of therapsids following extinction, but were facilitated by higher archosauromorph growth rates.


Effects of lick-contingent timeout on schedule-induced polydipsia.
Rats bar pressing on a 1-min fixed-interval schedule for 45-mg food pellets became polydipsic when water was concurrently available. They were then exposed to conditions in which each lick on the drinking tube produced a timeout period during which the food-schedule lever was retracted and the fixed-interval timer either did or did not continue to operate. Licks occurring within a timeout period extended its duration. As the duration of the lick-initiated timeout period was increased logarithmically through four values from 10 sec to 80 sec, lick rates as well as water intake rates generally decreased for all three subjects. As timeout duration was progressively increased, the rate of licks occurring in the absense of, but producing, timeouts decreased for all three rats, whereas the rate of licks occurring in the presence of timeout periods remained essentially constant. Water-intake rates and, with one exception, lick rates were suppressed more by timeout periods during which the fixed-interval timer did not continue to operate. These results indicate that lick-contingent timeout from positive reinforcement reduces schedule-induced drinking, and this suppressive effect is greater when the timeout period necessarily increases the interreinforcement interval beyond its minimum duration than when it does not.


Epidemiology of Squamous Cell Carcinoma of the Lip in the United States: A Population-Based Cohort Analysis.
Squamous cell carcinoma of the lip (lip SCC) composes more than 25% of all oral cancers. Most of the demographic and prognostic indicators for lip SCC are only available through retrospective case series. To examine the incidence, treatment, overall survival, and disease-specific survival (DSS) of patients with lip SCC. Population-based cohort analysis using the Surveillance, Epidemiology, and End Results database identified patients with lip SCC between January 1, 1973, and December 31, 2012. Overall survival and DSS. A total of 15 832 cases of lip SCC were identified. The cohort was composed of 12 945 men (81.8%) and 2887 women (18.2%). The mean age at diagnosis was 66.1 years. White patients accounted for 98.4% of the cases. Most of the tumors presented in the lower lip (77.8% external and 10.2% mucosal), whereas the external upper lip, mucosal upper lip, and the oral commissure represented 8%, 1%, and 1.2% of all cases, respectively. Of the patients, 91.2% underwent surgical therapy, 7.7% received radiation therapy, and 4.7% received both. Overall survival at 2 years, 5 years, and 10 years was 85.5%, 69.9%, and 50.2%, respectively. Multivariate analysis revealed that age, primary site, T stage, and N stage were determinants of overall survival and DSS. Kaplan-Meier survival analysis showed that SCC of the upper and lower lip had similar overall survival (163.6 months vs 163.8 months) and DSS (418.6 months vs 423.6 months). In contrast, SCC of the oral commissure had significantly lower overall survival (128.5 months) and DSS (286.7 months). Our study demonstrates that lip SCC predominantly affects white men in their mid-60s. The determinants of survival for lip SCC include age at diagnosis, primary site, T stage, and N stage. Squamous cell carcinoma of the upper lip and lower lip had similar survival, whereas SCC of the oral commissure was associated with decreased survival.


Skin sensitization potential of trisodium ethylenediaminetetraacetate.
A sodium salt of ethylenediaminetetraacetate (Na3EDTA) and ethylenediamine (EDA) were subjected to a repeated insult patch test on Hartley albino guinea pigs (10 per compound). All guinea pigs (10 of 10) receiving EDA were sensitized. None of the guinea pigs (0 of 10) was sensitized to Na3 EDTA. Likewise, none of the guinea pigs sensitized to EDA reacted positively when challenged with Na3 EDTA. Based on these results, it is concluded that EDTA is not likely to be a sensitizer to humans, and would not likely cross-sensitize with EDA. In addition, the presence of very small amounts of the sodium salts of EDTA in cosmetic and pharmaceutical preparations does not represent an appreciable risk of human skin sensitization.


What is new in chronic myeloid leukaemia?
Chronic myeloid leukaemia is a relatively rare condition, though it has stimulated widespread interest as a consequence of both the stem cell basis and the success of rationally designed therapies. This review will outline some of the issues involving the aetiology of the disease and how this relates to current and future therapies.


Experimental treatments for mitochondrial dysfunction in sepsis: A narrative review.
Sepsis is a systemic inflammatory response to infection. Sepsis, which can lead to severe sepsis, septic shock, and multiple organ dysfunction syndrome, is an important cause of mortality. Pathogenesis is extremely complex. In recent years, cell hypoxia caused by mitochondrial dysfunction has become a hot research field. Sepsis damages the structure and function of mitochondria, conversely, mitochondrial dysfunction aggravated sepsis. The treatment of sepsis lacks effective specific drugs. The aim of this paper is to undertake a narrative review of the current experimental treatment for mitochondrial dysfunction in sepsis. The search was conducted in PubMed databases and Web of Science databases from 1950 to January 2014. A total of 1,090 references were retrieved by the search, of which 121 researches met all the inclusion criteria were included. Articles on the relationship between sepsis and mitochondria, and drugs used for mitochondrial dysfunction in sepsis were reviewed retrospectively. The drugs were divided into four categories: (1) Drug related to mitochondrial matrix and respiratory chain, (2) drugs of mitochondrial antioxidant and free radical scavengers, (3) drugs related to mitochondrial membrane stability, (4) hormone therapy for septic mitochondria. In animal experiments, many drugs show good results. However, clinical research lacks. In future studies, the urgent need is to develop promising drugs in clinical trials.


Preservation of pancreas for transplantation.
For preservation of the pancreas, extracellular and intracellular solutions with aprotinin light microscopy showed both solutions to be suitable for a 3-hour preservation, though the intracellular solution appeared more suitable. Preservations for 6 and 24 hours have also been attempted, but these specimens showed fairly severe histological lesions.


Magnetic Graphene Field-Effect Transistor Biosensor for Single-Strand DNA Detection.
Herein, a magnetic graphene field-effect transistor biosensor was prepared through the transfer of a chemical vapor deposition graphene film onto a glass substrate to produce a sensing film and conductive channel. By fixing 1-pyrenebutanoic acid succinimidyl ester onto graphene film as an anchor, a probe aptamer was immobilized on the graphene film in order to capture magnetically labeled complementary single-stranded DNA. Our experiments showed that, within a periodic magnetic field, the biosensor impedance exhibited a periodic oscillation, the amplitude of which was correlated to the complementary DNA concentration. Based on this principle, the magnetic graphene field-effect transistor was utilized to detect single-stranded DNA with detection limition of 1 pM. The results were rationalized using a model wherein the magnetic force causes the DNA strand to bend, thereby resulting in magnetic nanobeads/DNA modulation of the double conductive layer of graphene transistors. Furthermore, since a periodic magnetic field could be introduced to produce a periodic impedance changes of MGFETs, sampling integration could be used to improve the signal-to-noise ratio efficiently by increasing the number of periods of the external magnetic field. Therefore, a novel biosensor for DNA detection with high sensitivity has been presented in this work. Based on the detection principle, this system may also be a potential tool for detecting other bio-molecules, cells, etc.


Psychotherapy in the #MeToo era: Ethical issues.
The #MeToo movement has heightened awareness of sexual assault and harassment, causing victims, perpetrators, observers, and loved ones to reflect on what constitutes sexual coercion and what signifies consent. These new conversations have had powerful effects: Survivors who were once silent have raised their voices; hundreds of men in powerful positions across the United States have been dismissed from their jobs; and societal norms related to sex and gender are being reconsidered. It is no wonder that the "national reckoning" enters the world of psychotherapy. This article explores three vignettes that consider therapeutic facilitation of apologies/reconciliations, psychotherapist values and advocacy, and men and #MeToo using the American Psychological Association Ethics Code as the basis to understand coercion and consent in this new cultural zeitgeist. The ethical, legal, and clinical ramifications inherent in these vignettes are highlighted as a way to assist psychotherapists in beginning to deal with #MeToo as it presents in psychotherapy. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Production of d-aldotetrose from l-erythrulose using various isomerases.
d-Aldotetroses are rare sugars that are obtained via chemical synthesis in low yield. In this study, we demonstrated that d-aldotetroses could be produced using 3 isomerases. First, l-erythrulose was epimerized using d-tagatose 3-epimerase from Pseudomonas cichorii ST-24. The specific optical rotation of the reaction solution gradually decreased to zero, indicating that approximately 50% of the l-erythrulose was converted to d-erythrulose. d, l-Erythrulose mixture was isomerized with d-arabinose isomerase from Klebsiella pneumoniae 40bXX to produce d-threose, resulting in a conversion rate of 9.35%. d-Erythrose production using l-rhamnose isomerase from Pseudomonas stutzeri LL172 resulted in a conversion rate of 12.9%. Because of the low purity of the purchased d-erythrose, the product was reduced by the Raney nickel catalyst compared with authentic erythritol. We confirmed the products using HPLC and 13C-NMR spectra. This is the first report of d-aldotetrose production using an enzymatic reaction.


On and off: proteasome and TGF-beta signaling.
Transforming growth factor-beta (TGF-beta) signaling mainly relies on the TGF-beta receptor-Smad pathway. Meanwhile, TGF-beta binding to its receptors initiates the degradation of several key components of its signaling pathway. The degradation of these components, including both positive and negative transducers, is mediated by the ubiquitin-proteasome system. Inhibition of the proteasome activity causes accumulation of these components in the cells and modulates TGF-beta signaling in a time-dependent and gene-specific manner. The accelerated degradation of TGF-beta signaling components via the proteasome system has been found in a number of tumors, indicating that dysregulated proteasomal degradation is a novel pathway how tumor cells silence TGF-beta signaling.


Animal models of atherosclerosis progression: current concepts.
The last decade has seen a number of important advances in the use of animal models of atherosclerosis progression. Small animal models, particularly mouse knockouts and rabbit models, are finding increasing use. This review discusses those models of particular research utility, highlights their advantages and limitations, and specifically addresses methodologies and current developments, in what is a rapidly changing field.


CNS-directed AAV2-mediated gene therapy ameliorates functional deficits in a murine model of infantile neuronal ceroid lipofuscinosis.
The neuronal ceroid lipofuscinoses (Batten disease) are a group of inherited neurodegenerative diseases characterized by the progressive intralysosomal accumulation of autofluorescent material in many cells, visual defects, seizures, cognitive deficits, and premature death. Infantile neuronal ceroid lipofuscinosis (INCL) has the earliest onset ( approximately 1.5 years of age) and is caused by a deficiency in the lysosomal enzyme palmitoyl protein thioesterase-1 (PPT1). Currently there is no effective treatment for children with INCL. In this study, newborn PPT1-deficient mice received two (cortex), four (cortex and hippocampus), or six (cortex, hippocampus, and cerebellum) bilateral intracranial injections of AAV2-PPT1. The AAV-treated animals had localized increases in PPT1 activity, decreased autofluorescent material, improved histologic parameters, and increased brain mass. In addition, the treated animals had dose-dependent improvements in a battery of behavioral tests and improved interictal electroencephalographic tracings. However, there was neither a significant decrease in seizure frequency nor an increase in longevity even in INCL animals receiving six injections. These data suggest that early treatment of INCL using gene transfer techniques can be efficacious. However, higher levels or a broader distribution of PPT1 expression, or both, will be required for more complete correction of this neurodegenerative disease.


Comparison of experiences of stress and coping between young people at risk of psychosis and a non-clinical cohort.
Although the experience of stress and associated coping responses are thought to play a role in the onset of schizophrenia and other psychotic disorders, there is little empirical evidence to support such a relationship. The relatively recent development of validated and reliable criteria for identifying young people at "ultra" high-risk (UHR) of psychosis has enabled the process of illness onset to be studied more closely than was previously possible. This longitudinal study compared the experiences of stress and coping between a UHR cohort (N=143) and a healthy comparison group (HC group, N=32). The UHR group experienced significantly fewer life events over a 12-month period than the HC group, but there was no difference in the experience of minor events or "hassles". However, the UHR group reported feeling significantly more distressed by events, felt they coped more poorly and utilized different coping strategies. The appraisals made about stressors differentiated the groups and was associated with differences in coping and distress levels. This suggests that treatment strategies focusing on stress management and enhancing coping skills might be important components of preventive interventions.


Living in silence: a grounded theory study of vulnerability in the context of HIV infection.
Clients with HIV infection have been conceptualized as a vulnerable population. Although some researchers have examined vulnerability with clients with HIV infection, a theory of vulnerability in the context of HIV infection is non-existent. The purpose of this study was to describe, using qualitative methodology, the process by which vulnerability occurs in the context of HIV infection. Grounded theory methodology was used to sample and analyze data from 15 qualitative interviews of adults with HIV infection. Data were collected until data saturation was reached. A theory that describes the process by which vulnerability occurs in the context of HIV infection, Living in Silence, emerged from the data. Living in Silence consists of four categories: Confronting Mortality and Illness, Struggling with Change, Encountering a Lack of Psychosocial Support, and Experiencing Vulnerability. Clients living with HIV experience vulnerability. Nursing interventions to decrease the risks of vulnerability should be directed toward the holistic needs of clients and toward increasing psychosocial support.


[Cauterization of the uterine cervix: electrocauterization and cryotherapy].
The authors review the controversies that still continue concerning electrocauterization of the uterine cervix. They emphasize the value of colposcopy in the evaluation of the cervix. This examination is indispensable in selecting the cases for treatment: ectropion and benign malpighian dysplasias are clear indications for cauterization. Contraindications and technical problems are discussed. The indications are given for bipolar biactive, and bipolar monoactive electrocauterization, respectively, or for electroresection by means of a metallic loop. The different cicatrization times after electrocauterization are reviewed as well as the possibility of sequelae: in certain cases sequelae can be more or less avoided by previous therapeutic precautions and by careful attention to the duration of cauterization. Cauterization of the uterine cervix by cryotherapy seems to be worthy of particular consideration: the first results are reported. It seems to be simpler to use than diathermocauterization and in the great majority of cases the results seem to have been good.


Two-year prospective evaluation of the factors affecting honeymoon frequency and duration in children with insulin dependent diabetes mellitus: the key-role of age at diagnosis.
The aim of this study was to investigate the influence of pre-treatment variables on subsequent insulin requirement (IR) and partial remission (PR) in children with insulin-dependent diabetes mellitus (T1DM). Sixty-seven children with newly diagnosed T1DM, admitted to our Clinic during a 3-year recruitment period, were longitudinally evaluated for 2 yr. Patients were characterized by sex, age, parental education, duration of symptomatic history at diagnosis, admission duration, ketoacidosis or absence of ketoacidosis and residual beta-cell activity. More than 80% of the children experienced a PR, which lasted more than 12 months in 41.7% and at least 24 months in 16.4% of cases. The prevalence of PR at different ages after T1DM onset was significantly lower in children diagnosed while younger than 5 years than in those diagnosed after 5 years. The mean duration of the remission period was 11.7 +/- 8.9 months, irrespectively of sex, duration of the symptomatic period preceding T1DM diagnosis, parental education, blood pH and base excess, HbA1c concentration and admission duration. Beta-cell residual function evaluated after glucagons stimulation test (basal and 6 min C-peptide) was statistically different in PR patients and in those who experienced no remission. Age at diagnosis was the only pre-treatment factor which, on stepwise regression analysis, affected both PR duration and IR at the end of follow-up. To conclude, honeymoon frequency and duration are strictly conditioned by both residual beta-cell function and IR at T1DM onset. Since IR is higher in younger subjects, early onset of T1DM can be considered the factor with the most detrimental influence on honeymoon incidence. Other pre-treatment variables have no significant impact on PR.


Development of the First Health-Related Quality of Life Questionnaires in Arabic for Women with Polycystic Ovary Syndrome (Part I): The Creation and Reliability Analysis of PCOSQoL-47 and PCOSQoL-42 Questionnaires.
Background and objective We lack a reliable and validated health-related quality of life (HRQoL) questionnaire to measure the negative impact of polycystic ovary syndrome (PCOS) on the various aspects of the lives of Arabic women, which addresses sexuality in married women only. Hence, we aimed to develop two separate, simple, reliable, validated, and easily interpretable HRQoL questionnaires in Arabic for married and unmarried women with PCOS for effective QoL evaluation. Materials and methods The development and reliability analysis of the Polycystic Ovary Syndrome Quality of Life (PCOSQoL)-47 and PCOSQoL-42 involved two quantitative and qualitative phases. Phase 1 included retrieval of 158 items from 584 PubMed articles, item reduction, Arabic translation, content and face validity testing, creation of a five-domain draft (53 items for married and 45 items for unmarried women), with no sexuality domain for unmarried women. Phase 2 involved test-retest reliability, which involved using the Spearman's correlation, Wilcoxon nonparametric signed-rank, and internal consistency using Cronbach's-alpha, inter-item, and intraclass correlation (ICC) coefficients, as well as creating a second draft (47 items for married and 42 items for unmarried women). Results The content validity indices testing by 26 healthcare experts decreased the item pool to 57 items for married and 45 items for unmarried women. Face validity by another 30 experts and 30 women from each group resulted in a further reduction to 53 items for married and 45 items for unmarried women, to be tested in a pilot study, which included another 30 women from each group. Test-retest reliability analysis by 195 married and 173 unmarried women revealed significantly excellent redundancy, reliability, and stability of items (highly significant Cronbach's alpha and ICC by internal consistency testing), and reduced the item pool to 47 items for married and 42 items for unmarried women. Conclusions Both questionnaires were found to be highly reliable for the HRQoL evaluation among both married and unmarried Arabic women with different phenotypes of PCOS.


Effect of Exergaming on Quality of Life, Fatigue, and Strength and Endurance Muscle in Cancer Patients: A Randomized Crossover Trial.
Objective: To analyze the influence of exergaming (EXE) quality of life, cancer-related fatigue (CRF), electromyography, and strength and endurance muscle in a randomized crossover trial. Methods: We conducted a single-blinded, randomized, and crossover trial, which included 38 cancer volunteers undergoing chemotherapy (Age = 60.07 ± 12.10 years; body mass index = 26.79 ± 5.33 kg/m2). All volunteers were randomized into two intervention moments: EXE and without intervention (WI) and after 1-month washout period of crossing of the evaluated moments. The intervention was performed on an EXE protocol using Xbox 360 Kinect®, with the game "Your Shape Fitness Evolved 2012" two to three times per week for 20 sessions. All volunteers were assessed the CRF and quality-of-life levels through the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire, the median frequency (MDF) by surface electromyography, maximal voluntary isometric contraction (MVIC), and the muscle endurance time at 80% MVIC of the dorsiflexors and plantar flexors using dynamometer. Results: In the comparison between EXE and WI moments, were observed increase in the scores for quality of life (P < 0.001), subscale fatigue (P < 0.001), in the MDF values of right lateral gastrocnemius muscles: P = 0.017, muscle endurance time (left dorsiflexion [LDF]: P < 0.001; right dorsiflexion [RDF]: P < 0.001; left plantar flexion [LPF]: P < 0.001; RPF: P = 0.039), and muscle strength (LDF: P < 0.001; RDF: P < 0.001; LPF: P = 0.002). Conclusion: The crossover study, the EXE protocol promoted improvement in cancer-related fatigue (CRF) and quality of life, increased MVIC, endurance time, and MDF values of the dorsiflexor and plantar flexor muscles of cancer volunteers undergoing chemotherapy.


Simplet/Fam53b is required for Wnt signal transduction by regulating β-catenin nuclear localization.
Canonical β-catenin-dependent Wnt signal transduction is important for several biological phenomena, such as cell fate determination, cell proliferation, stem cell maintenance and anterior-posterior axis formation. The hallmark of canonical Wnt signaling is the translocation of β-catenin into the nucleus where it activates gene transcription. However, the mechanisms regulating β-catenin nuclear localization are poorly understood. We show that Simplet/Fam53B (Smp) is required for Wnt signaling by positively regulating β-catenin nuclear localization. In the zebrafish embryo, the loss of smp blocks the activity of two β-catenin-dependent reporters and the expression of Wnt target genes, and prevents nuclear accumulation of β-catenin. Conversely, overexpression of smp increases β-catenin nuclear localization and transcriptional activity in vitro and in vivo. Expression of mutant Smp proteins lacking either the nuclear localization signal or the β-catenin interaction domain reveal that the translocation of Smp into the nucleus is essential for β-catenin nuclear localization and Wnt signaling in vivo. We also provide evidence that mammalian Smp is involved in regulating β-catenin nuclear localization: the protein colocalizes with β-catenin-dependent gene expression in mouse intestinal crypts; siRNA knockdown of Smp reduces β-catenin nuclear localization and transcriptional activity; human SMP mediates β-catenin transcriptional activity in a dose-dependent manner; and the human SMP protein interacts with human β-catenin primarily in the nucleus. Thus, our findings identify the evolutionary conserved SMP protein as a regulator of β-catenin-dependent Wnt signal transduction.


High-yield one-pot synthesis of polyrotaxanes with tunable well-defined threading ratios over a wide range.
In this work, we report a high-yield one-pot synthesis of polyrotaxane (PR), composed of (2-hydroxypropyl)-α-cyclodextrin (hpCD) and polyethylene glycol (PEG), with well-defined hpCD threading ratios controllable across a wide range from 0.64% to 10%. In hpCD/PEG aqueous solutions, hpCDs are well dispersed and threaded spontaneously into hpCDs to form a pseudo-PR (pPR) structure. The homogeneous dispersion of hpCDs results in a well-defined threading ratio of hpCDs on PEG, which is suggested by the fact that the dispersity of the molecular weight distribution of PR is almost the same as that of pure PEG. The well-defined hpCD threading ratio of the PRs can be controlled over a wide range by tuning the hpCD concentration in the pPR solutions.


Human epidermal Langerhans cells replenish skin xenografts and are depleted by alloreactive T cells in vivo.
Epidermal Langerhans cells (LC) are potent APCs surveying the skin. They are crucial regulators of T cell activation in the context of inflammatory skin disease and graft-versus-host disease (GVHD). In contrast to other dendritic cell subtypes, murine LC are able to reconstitute after local depletion without the need of peripheral blood-derived precursors. In this study, we introduce an experimental model of human skin grafted to NOD-SCID IL2Rγ(null) mice. In this model, we demonstrate that xenografting leads to the transient loss of LC from the human skin grafts. Despite the lack of a human hematopoietic system, human LC repopulated the xenografts 6 to 9 wk after transplantation. By staining of LC with the proliferation marker Ki67, we show that one third of the replenishing LC exhibit proliferative activity in vivo. We further used the skin xenograft as an in vivo model for human GVHD. HLA-disparate third-party T cells stimulated with skin donor-derived dendritic cells were injected intravenously into NOD-SCID IL2Rγ(null) mice that had been transplanted with human skin. The application of alloreactive T cells led to erythema and was associated with histological signs of GVHD limited to the transplanted human skin. The inflammation also led to the depletion of LC from the epidermis. In summary, we provide evidence that human LC are able to repopulate the skin independent of blood-derived precursor cells and that this at least partly relates to their proliferative capacity. Our data also propose xeno-transplantation of human skin as a model system for studying the role of skin dendritic cells in the efferent arm of GVHD.


Vitamin D metabolites in diabetic patients: decreased serum concentration of 24,25-dihydroxyvitamin D.
In order to elucidate if changes in vitamin D metabolism play a role for diabetic bone loss, the serum concentrations of the major vitamin D metabolites were studied in 26 adult male ambulatory insulin-treated diabetics, selected to have normal renal function and a duration of diabetes below 11 years. The patients were studied during usual metabolic control and exhibited wide ranges of hyperglycaemia and glycosuria. The serum concentrations of the major metabolites of vitamin D, 25-hydroxyvitamin D(2 + 3) (25OHD), 24,25-dihydroxyvitamin D(2 + 3) (24,25(OH)2D), and 1,25-dihydroxyvitamin D(2 + 3) (1,25(OH)2D), were measured in diabetics, and in age and sex matched controls. The diabetics had slightly decreased serum levels of 25OHD (42.0 nmol/l versus 55.5 nmol/l in normals, P less than 0.05), markedly decreased serum levels of 24,25(OH)2D (2.98 nmol/l versus 5.91 nmol/l, P less than 0.01), but serum levels of 1,25(OH)2D were virtually normal (64.2 pmol/l versus 68.3 pmol/l, ns). The close correlation between serum concentrations of 25OHD and 24,25(OH)2D observed in the normal subjects, was absent in the diabetics. There were no correlations between the serum levels of any of the vitamin D metabolites and the measured indices of glucose and calcium metabolism. It is concluded that insulin-dependent diabetic patients demonstrate definite alterations in serum levels of vitamin D metabolites, the significance of which remains unknown at present.


Differentiation among parkinsonisms using quantitative diffusion kurtosis imaging.
Differential diagnoses among Parkinson's disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy syndrome (PSPS) are often difficult. Hence, we investigated whether diffusion kurtosis imaging (DKI) could detect pathological changes that occur in these disorders and be used to differentiate between such patients. Fourteen patients (five with PD, four MSA, and five PSPS) and six healthy controls were examined using a 1.5-T scanner. Mean kurtosis (MK), fractional anisotropy, and mean diffusivity maps were generated, and these values of the midbrain tegmentum (MBT) and pontine crossing tract (PCT), as well as MBT/PCT ratios, were obtained. We found no significant differences in MBT and PCT values on DKI maps among the groups. In contrast, MBT/PCT ratios from MK maps were significantly increased in the MSA group and decreased in the PSPS group compared with the other groups. MBT/PCT ratios from mean diffusivity maps showed a significant increase in the PSPS group. Therefore, quantitative DKI analyses, particularly the MBT/PCT ratio from MK maps, can differentiate patients with parkinsonisms.


Characterization of dentin formed in transplanted rat molars by electron probe microanalysis.
The present study was designed to characterize dentin formed in transplanted rat molars by investigating calcium (Ca), phosphorus (P), and magnesium (Mg) concentrations using electron probe microanalysis (EPMA) as well as examining the rate of dentin matrix formation by vital staining. The unerupted immature lower right second molar in 2-week-old rats was transplanted into the upper right first molar socket. Rats were injected with oxytetracycline, calcein, and alizarin intraperitoneally at 1 day before and 1 and 2 weeks after transplantation, respectively, for vital staining. The maxillae and mandibles were fixed 3 weeks after transplantation, resected, and embedded in resin. Undemineralized sections were cut and examined by fluorescent microscopy and EPMA. The thickness of dentin formed in the first week after transplantation was significantly less than that of dentin formed in any other 1-week period in the transplanted tooth and was about one-fifth the thickness of dentin formed in control teeth. Formation of dentin recovered in the third week after transplantation. In the first week after transplantation, EPMA demonstrated a sharp increase in Mg concentration with a slight decrease in Ca concentration. Thereafter, no significant difference was identified among Ca, P, or Mg concentrations or the Ca/P ratio between transplanted and control teeth. These results suggest that disruption of the circulation and innervation by transplantation cause a temporary change in the matrix formation rate and elemental distribution of dentin, which is subsequently restored within 2 weeks after transplantation.


Comparison of cyclosporine A with methylprednisolone for treatment of canine atopic dermatitis: a parallel, blinded, randomized controlled trial.
The objective of this multicentre, parallel, blinded, randomized controlled study was to evaluate the efficacy and the safety of cyclosporine (CsA group, 117 dogs) in comparison with methylprednisolone (MP group, 59 dogs) in the treatment of atopic dermatitis for 4 months. Mean induction dose of both drugs (5 mg/kg CsA, 0.75 mg/kg MP) was tapered over time according to the clinical response. At the end of the study, the mean estimated percentage reduction from baseline (confidence interval) of lesion scores was 52% (44-59) and 45% (35-56), and the reduction in pruritus score was 36% (27-43) and 33% (23-43) in dogs in the CsA and MP groups, respectively. These percentages were not significantly different between groups. A significantly better overall assessment of efficacy was obtained in the CsA-treated dogs (76 vs. 63% responses excellent or good in the CsA compared with MP group). CsA-treated dogs presented a higher frequency of gastrointestinal disorders, mainly vomiting, but MP dogs tended to be more susceptible to infections. There was no remarkable change over baseline of the haematological and biochemical parameters in the two groups.


Spore coat formation and timely sporulation depend on cellulose in Dictyostelium.
Cellulose is a major component of the extracellular coat that surrounds the terminally-differentiated spore of Dictyostelium. It is sandwiched between two layers of proteins that derive from prespore vesicles by exocytosis. Strains unable to synthesize cellulose due to null mutations in the gene encoding the catalytic subunit of cellulose synthase (dcsA) failed to make detergent-resistant spores but produced small, highly refractile, round spore-like cells up to a day late. Although these cells resembled spores in appearance, they were unstable, only transiently ellipsoid in shape, and sensitive to hypo-osmotic shock, drying, or detergents. Differentiation of these pseudo-spores was induced in the normal time frame by activation of the cAMP-dependent protein kinase or co-development with wild type cells, and coat proteins were secreted by the dcsA-null cells at the same time as wild type cells. A substantial fraction of secreted coat proteins was loosely associated with the surface of the mutant cells, resembling the precoat posited to form early during normal sporulation. Transmission electron microscopy revealed that the precoat had little ultrastructural organization in the absence of cellulose. Thus, cellulose in the coat appears to be required for the organization of the pre-coat precursors as well as the stability, dormancy, and shape of the spore.


[Desorption of polycyclic aromatic hydrocarbons in soils assisted by SPMD].
In order to develop a new method to study the desorption and bioavailability of hydrophobic organic chemicals (HOCs) in soils, a method using semi-permeable membrane device (SPMD) to study desorption of HOCs in soils has been set up, and assisted desorption of polycyclic aromatic hydrocarbons (PAHs), phenanthrene(PHE), pyrene(PYE), and benzo[a] pyrene (B[a]PYE) in three different kinds of soils was studied using SPMD. The results show that SPMD is a good measurement to study the desorption and bioavailability of HOCs in soils. SPMD assisted desorption of PAHs is highly dependent on the properties of the soils and the chemicals. PHE and PYE desorption percentages increase with the reduction of the content of soil organic matter (SOM), so that the desorption of the two chemicals increases from 56.45% and 48.28% to almost 100% when SOM content was reduced from 18.68% to 0.3%. However, clay has a significant holding effect on B[a]PYE, and PYE desorption is only 66.97% in Soil 3 with SOM of 0.3% and clay content of 39.05%. There is a great variety in the desorption among the different PAHs. With the reduction of SOM content and the elevation of contamination concentration, the difference between PHE and PYE decreases gradually, while B[a]PYE exhibits a significant difference from them. This could be attributed to the high lipophilicity and large molecular size of B[a]PYE, which make the molecule of B[a]PYE to be more easier to be held in the nanopores of clay and the dense region of SOM.


Biological and genetic characteristics of tumor-initiating cells in colon cancer.
Human prominin-1 (PROM1, CD133) was used as a marker to detect stem cells (progenitor cells) and cancer stem cells (tumor-initiating cells) in various tissues. The purpose of this study was to investigate the biological and genetic characteristics of tumor-initiating cells in colon cancer with both in vitro and in vivo analyses. The CD133 expression of 12 colon cancer cell lines was evaluated. CD133+ cells were isolated by flow cytometry and examined for in vivo tumor formation, in vitro proliferation, colony formation, and invasion ability. Additionally, we used microarray analysis to compare gene expression profiles between CD133+ and CD133- isolated cells. CD133+ cells were found in 5 of 12 colon cancer cell lines. Isolated CD133+ cells from the HT29 colon cancer cell line exhibited a higher tumorigenic potential than CD133- cells in the in vivo tumor formation assay. Furthermore, it was shown that CD133+ cells are more proliferative and have higher colony-forming and invasive abilities than CD133- cells in vitro. Microarray analysis found differential gene expression correlating with CD133 expression. It was confirmed that CD133+ cells in colon cancer are useful markers for the detection of tumor-initiating cells. Intimate biological and genetic features of CD133+ cells in colon cancer cell lines were also revealed. The biological characteristics of CD133+ cells and differentially expressed genes in these cells will help elucidate more details of tumor-initiating cells in colon cancer.


A hybrid ZIF-8/ZIF-62 glass membrane for gas separation.
Metal-organic framework (MOF) glasses have demonstrated great potential for high-performance separation. Herein a uniform hybrid MOF glass membrane was fabricated by using the liquid state of ZIF-62 to facilitate the melting of ZIF-8. The doping of ZIF-8 enhanced both the adsorption capacity as well as the ideal C3H6/C3H8 selectivity of ZIF-62 glass. As expected, the hybrid glass membrane exhibited good C3H6/C3H8 separation performance while preserving the CO2 performance of the sole ZIF-62 membrane.


Glomerular lesions in patients with sickle cell disease.
Sickle cell disease (SCD) is an increasing cause of chronic kidney disease, but the spectrum of glomerular lesions and their underlying mechanisms remain poorly described. We reviewed 18 renal biopsies from patients with SCD and glomerular involvement and studied the expression of hypoxic markers in the biopsy specimens. Four histopathologic variants were distinguished: focal segmental glomerulosclerosis (FSGS) (39%), membranoproliferative glomerulonephritis (28%), thrombotic microangiopathy glomerulopathy (17%), and specific sickle cell disease glomerulopathy (17%). Chronic organ damage and history of acute chest syndrome were associated with the occurrence of SCD glomerulopathy. All patients exhibited macroalbuminuria but only 6 patients displayed impaired renal function. SCD was not associated with a specific FSGS histologic variant. Long-term follow-up analysis revealed that 50% of patients exhibited chronic kidney disease. Regardless of the histologic variants, immunohistochemistry did not reveal a specific induction of hypoxic markers (inducible nitric oxide synthase [iNOS], nitrotyrosine, hypoxia-inducible factor [HIF]-1 alpha) at the time of renal biopsy. This large study shows that a wide spectrum of glomerular lesions is associated with SCD. Whatever lesions are observed, the renal prognosis is poor, and early renoprotective treatment is necessary. Hypoxic state does not seem to play a key role in the progression of glomerular lesions, but its potential role at an early stage of glomerular injury requires further investigation.


Glucantime efficacy in the treatment of zoonotic cutaneous leishmaniasis.
Pentavalent antimony (SbV) compounds are still considered the first line of treatment for all forms of leishmaniasis. There have been reports of drug resistance and unresponsiveness to treatment with these drugs. We investigated the clinical response to treatment of cutaneous leishmaniasis with glucantime, the drug of choice for all forms of leishmaniasis in Iran. All individuals suspected of cutaneous leishmaniasis from October 2007 to March 2008 were included in the study if met specific criteria. After laboratory diagnosis and parasite identification by PCR, 43 patients agreed to participate and complete the protocol for treatment. Meglumine antimoniate (glucantime) was given at a dose of 20 mg/kg/day for 20 days (two 10-day periods) according to a World Health Organization (WHO) recommended protocol. Response to treatment was evaluated 6 weeks after initiation of treatment. Fifteen patients (34.9%) were clinically unresponsive to glucantime treatment while the remaining 28 patients (65.1%) responded to treatment. There were no statistically significant differences by occupation, gender, chronicity of the disease before starting treatment, number of lesions, or age between the glucantime sensitive and resistant patients. Our study showed a significant level of unresponsiveness to glucantime among patients with cutaneous leishmaniasis caused by Leishmania major in Iran. These findings highlight the need for new treatment regimens.


Arabidopsis class I KNOTTED-like homeobox proteins act downstream in the IDA-HAE/HSL2 floral abscission signaling pathway.
Floral organ abscission in Arabidopsis thaliana is regulated by the putative ligand-receptor system comprising the signaling peptide INFLORESCENCE DEFICIENT IN ABSCISSION (IDA) and the two receptor-like kinases HAESA and HAESA-LIKE2. The IDA signaling pathway presumably activates a MITOGEN-ACTIVATED PROTEIN KINASE (MAPK) cascade to induce separation between abscission zone (AZ) cells. Misexpression of IDA effectuates precocious floral abscission and ectopic cell separation in latent AZ cell regions, which suggests that negative regulators are in place to prevent unrestricted and untimely AZ cell separation. Through a screen for mutations that restore floral organ abscission in ida mutants, we identified three new mutant alleles of the KNOTTED-LIKE HOMEOBOX gene BREVIPEDICELLUS (BP)/KNOTTED-LIKE FROM ARABIDOPSIS THALIANA1 (KNAT1). Here, we show that bp mutants, in addition to shedding their floral organs prematurely, have phenotypic commonalities with plants misexpressing IDA, such as enlarged AZ cells. We propose that BP/KNAT1 inhibits floral organ cell separation by restricting AZ cell size and number and put forward a model whereby IDA signaling suppresses BP/KNAT1, which in turn allows KNAT2 and KNAT6 to induce floral organ abscission.


Removal of infected canine cemented total hip prostheses using a femoral window technique.
To evaluate a femoral window technique for retrieval of cemented total hip prostheses. Retrospective clinical study. Twelve dogs with infection of a cemented modular total hip prosthesis. Implant removal was performed by an extended craniolateral approach to the hip and proximal femur without trochanteric osteotomy. The femoral cement mantle was fragmented and removed with simple orthopedic instrumentation by a lateral femoral window that was repaired using cerclage wires. Surgical technique, intraoperative and postoperative complications, bacterial culture results, histopathologic findings, and completeness of cement removal were recorded. Follow-up radiographs were taken 5 to 9 weeks postoperatively. Long-term follow-up information was obtained by client questionnaire. Functional outcome was assessed by scoring ability to stand, sit, walk, run, play, climb stairs, and get into a car. Prosthesis retrieval was performed 2 to 41 months after implantation (median, 14 months). Complete removal of femoral cement was achieved in 10 dogs. A nondisplaced femoral fissure, extending proximally from the window, was an intraoperative complication in 2 dogs. Staphylococcus spp was most commonly isolated (6 dogs) from interfacial membrane samples. Systemic antibiotic therapy, dependent on susceptibility testing, was administered for 3 to 10 weeks postoperatively. There was radiographic evidence of osteotomy healing at 5- to 9-week reassessment. Recurrence of osteomyelitis was not observed. Long-term functional outcome was considered mildly abnormal. The lateral window was an effective technique for retrieval of retained femoral cement. Removal of an infected prosthesis using this technique generally resulted in a clinical outcome comparable to that with ab initio femoral head and neck excision.


[Diffuse pigmented villonodular synovitis in the shoulder joint and the biceps tendon: a case report].
Pigmented villonodular synovitis (PVNS) is a benign proliferative disease of synovium frequently most frequently seen in the knee joint and hand tendon synovial tissues; shoulder involvement is extremely rare. It can be seen in joints in two forms as nodular or diffuse involvement. The clinical and radiological symptoms are not specific to the disease and usually mimic other joint diseases. The general complaint of the patients is long-lasting painful swelling that could not be diagnosed. In magnetic resonance imaging it is observed as soft tissue mass. Pigment deposition and histiocytic cell infiltration in the villous synovial projections are the major histological findings. Synovectomy is performed for treatment and the incidence of recurrence is high. In this article, we report a 23-years-old male patient with diffuse PVNS in the shoulder joint and biceps tendon which are rarely involved in PVNS.


Use of a monoclonal antibody recognizing a cell surface determinant to distinguish prestalk and prespore cells of Dictyostelium discoideum slugs.
Double labelling experiments on Dictyostelium discoideum cells at different developmental stages were carried out using monoclonal antibodies MUD1 (prespore specific), MUD9 (strong label on prestalk and anterior-like cells) and a fluorescence-activated cell sorter. The monoclonal antibody MUD9, which recognizes the surface of prestalk and anterior-like cells strongly and prespore cells weakly, is also present on the surface of vegetative amoebae and on mature stalk cells but not on the spore surface. Sharing of an antigenic determinant between vegetative, prestalk and anterior-like cells is consistent with these cells being 'less differentiated' than prespore cells.


Teaching clinical research methodology to the academic medical community: a fifteen-year retrospective of a comprehensive curriculum.
Due to inadequate preparation, many medical professionals are unable to critically evaluate published research articles or properly design, execute and present their own research. To increase exposure among physicians, medical students, and allied health professionals to diverse methodological issues involved in performing research. A comprehensive course on research methodology was newly designed for physicians and other members of an academic medical community, and has been successfully implemented beginning 1991. The role of the study hypothesis is highlighted; interactive pedagogical techniques are employed to promote audience engagement. Participants complete an annual evaluation to assess course quality and perceived outcomes. Outcomes also are assessed qualitatively by faculty. More than 500 physicians/other professionals have participated. Ratings have been consistently high. Topics deemed most valuable are investigational planning, hypothesis construction and study designs. An enhancement of capacity to define hypotheses and apply methodological concepts in the criticism of scientific papers and development of protocols/manuscripts has been observed. Participants and faculty believe the course improves critical appraisal skills and ability to conduct research. Our experience shows it is feasible to accomplish these objectives, with a high level of satisfaction, through a didactic program targeted to the general academic community.


Prognostic factors affecting the short-term efficacy of non-surgical treatment of chronic periodontitis: a multilevel modeling analysis.
This study is aimed to analyze the prognostic factors affecting the short-term efficacy of non-surgical treatment of patients in periodontitis from stage II to stage IV by the multilevel modeling analysis. A total of 58 patients with chronic periodontitis were included in this study. Patients were clinically explored before and 3 months after the treatment and the difference in probing depth was determined [Reduction of probing depth (Δ PD) = baseline PD - finial probing depth (FPD)] which is considered as the therapeutic evaluation. Three different levels were analyzed: patients, teeth and sites to construct a multi-layer linear model. Probing depth (PD) improved significantly compared with that before treatment (p < 0.05), in which FPD was (3.90 ± 1.39) mm, and the ΔPD was (1.79 ± 0.97) mm. Compared with the mesial sites and distal sites of the multi-rooted teeth, the number of PD ≥ 5 mm or PD < 5 mm after the treatment was significantly different (P < 0.05), and the proportion of PD < 5 mm was higher in mesial sites. The null model showed that Δ PD varied greatly between groups at various levels (P < 0.001), with prediction variable of site level, tooth level, and patient level accounted for 66%, 18%, and 16% of the overall difference, respectively. The complete model showed that the Δ PD of smokers was significantly lower than that of non-smokers (P < 0.001). The Δ PD of the mesial and distal sites was larger than that of the buccolingual central site (P < 0.001). The Δ PD of single-rooted teeth was larger than that of multi-rooted teeth (P < 0.001). The baseline PD, tooth mobility (TM), bleeding index (BI), clinical attachment loss (CAL) were significantly negatively correlated with Δ PD (P < 0.001). Patients with periodontitis from stage II to stage IV, who were non-smoking, have good compliance, good awareness of oral health, and low percentage sites with PD ≥ 5 mm at baseline, single-rooted teeth with hypomobility, less clinical attachment loss and lower bleeding index and sites of mesial or distal can obtain an ideal short-term efficacy of non-surgical treatment.


Comparison of liquid chromatography-tandem mass spectrometry with a commercial enzyme-multiplied immunoassay for the determination of plasma MPA in renal transplant recipients and consequences for therapeutic drug monitoring.
Mycophenolic acid (MPA) is an immunosuppressive drug partly metabolized to MPA-glucuronide (MPAG), which is pharmacologically inactive. The currently available enzyme-multiplied immunoassay technique (EMIT) has been reported to overestimate MPA plasma concentration in clinical samples when compared with HPLC techniques. The aims of this study were to design and validate a specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique for the determination of MPA and MPAG using a low plasma volume and a simple sample preparation procedure; then to compare it with EMIT for the determination of MPA in plasma samples collected over an interdose interval at different posttransplantation periods (days 3, 7, and 30 and after 3 months) in 25 renal transplant recipients orally administered cyclosporine and mycophenolate mofetil twice daily, to investigate the origins of the differences between techniques. The LC-MS/MS technique developed showed limits of quantification (LOQs) of 0.1 mg/L and 1 mg/L for MPA and MPAG, respectively, and was linear, accurate, and precise from these LOQs up to 30 mg/L for MPA and 300 mg/L for MPAG. EMIT gave similar results to LC-MS/MS for spiked quality control samples (in a synthetic matrix or in drug-free plasma) but significantly overestimated MPA levels in clinical samples: EMIT - LC-MS/MS = +61.39% +/- 57.94%, with large variations depending on patients, time elapsed since transplantation, sampling time, and concentration levels. These results confirmed the known overestimation of the EMIT assay compared with a specific method and showed that the magnitude of this overestimation depended on sampling time and time after transplantation.


Bone tissue microscopic findings related to the use of diode laser (830 nm) in ovine mandible submitted to distraction osteogenesis.
To analyze the microscopic characteristics of the effect of Gallium-Aluminum Arsenid diode laser (GaAlAs - 830etam) applied during the activation and consolidation period to ovine mandibles submitted to distraction osteogenesis. Eighteen sheep underwent surgery in order to have bone distractors implanted in the left side of the jaw area. They were divided into three groups: 1 - Control; 2 - Laser irradiation during the activation period; 3 - Laser irradiation during the fixation period. The irradiation was carried out in five sessions, on every other day, with 4,0J/cm(2) doses applied to four pre-established areas, totaling 16J per session. After four days of latency under post-operative care, ten days of distractor activation (at 1mm/day) and twenty-one days of fixation the animals were sacrificed and the devices removed for microscopic analysis. The groups that received laser irradiation (GaAlAs) presented a greater amount of mineralized bone trabeculae when compared to the Control Group. Despite that, cartilaginous tissues were also found in Group 2. The laser has been more favorable when used in the consolidation period, after bone elongation.


PPARs and their effects on the cardiovascular system.
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear receptor superfamily that undergo transactivation or transrepression by distinct mechanisms leading to induction or repression of expression of target genes. The PPAR family consists of three isoforms, α, γ, and ß/δ, which share similar structural organization, possess distinct functions, and vary in their ligand affinity, expression, and activity in different metabolic pathways in different tissues. PPARs are involved in many functions especially those involved in the regulation of vascular tone, inflammation and energy homeostasis and therefore represent important targets for hypertension, obesity, obesity-induced inflammation, and metabolic syndrome in general. PPARs may influence the inflammatory response either by direct transcriptional downregulation of proinflammatory genes via mechanisms involving transrepression, or indirectly via their transcriptional effects on lipid metabolism. On account of their pleiotropic effects, they are now known to be active participants in many disease conditions and they represent potent targets for the development of therapy of a wide array of diseases.


SARS-CoV-2 Omicron Variant in Patients With Chronic Myeloid Leukemia: A Retrospective Study.
Background and aims Coronavirus disease 2019 (COVID-19) is caused by a virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the first pandemic wave, SARS-CoV-2 had developed significant changes and mutations that resulted in the emergence of different strains. Each strain varies in its virulence and disease severity. Most reports have shown that the Omicron variant causes mild illness. Little is known about the impact of Omicron in patients with chronic myeloid leukemia. We present patients with chronic myeloid leukemia who had infection with the Omicron variant of the SARS-CoV-2 and their outcomes. Materials and methods Retrospective data from the records of the National Center for Cancer Care and Research from December 20, 2021, to January 30, 2022. Participants were adults over the age of 18 years with Omicron infection who had been diagnosed with chronic myeloid leukemia according to World Health Organization classifications from 2008 and 2016. Results Eleven patients with chronic myeloid leukemia had Omicron infection. All patients had a mild disease according to the World Health Organization classification of COVID-19 severity. The majority of patients were young males. Conclusions In patients with chronic myeloid leukemia, infection with the Omicron variant of the SARS-CoV-2 usually results in mild disease not requiring hospitalization.


SPECT using asymmetric pinholes with truncated projections.
Tomographic systems employing truncated projections have been developed for parallel and fan beam collimation and for cone beam CT but the idea has not been extensively explored in pinhole single photon emission computed tomography (SPECT). In this paper, we explore the sampling requirements and system performance of SPECT systems with asymmetric pinhole collimators and truncated projections. We demonstrate that complete 3D sampling can be achieved by using multiple detectors with truncated asymmetric pinholes, offset axially from each other, and a spiral orbit. The use of truncated projections can be exploited in the design of pinhole SPECT systems by moving the pinholes closer to the subject, resulting in increased sensitivity and improved spatial resolution. Truncated and untruncated pinhole systems were evaluated using the contrast-to-noise ratio (CNR) calculated from the linearized local impulse response as a figure of merit. The CNR for the truncated pinhole system was up to 60% greater than that for the untruncated system at matched resolution for a source voxel near the centre of a uniform phantom and 30% greater at the edge. We conclude that an object can be reconstructed from asymmetric pinholes with truncated projections, which leads to potentially important design considerations and applications in single- and multi-pinhole SPECT.