Interferon-gamma Expression Profile as Diagnostic Signatures of Unexplained Infertility in Female Patients Suffer from Hashimoto's Thyroiditis.
Diagnosis of unexplained infertility (UEI) is made by exclusion and a relatively common problem that affects couples worldwide. Unfortunately, it is a not uncommon for females to suffer from Hashimoto's thyroiditis (HT). Interferon-gamma (IFN- γ) has a central key role in HT and in the ability to conceive. We aimed to estimate serum IFN- γ level and its expression profile in Egyptian women with HT and assess their possible association with UEI. In this study, we examined 120 women with HT. We evaluated fertility in all patients; female patients who suffer from UEI were detected. Diagnosis of HT was based on the clinical data and the laboratory measures, enzyme-linked immunosorbent assay was used to measure serum IFN- γ, and the expression of IFN-γ messenger ribonucleic acid (mRNA) was assayed by real-time polymerase chain reaction (PCR). According to the results of this study, 37.5 % of the studied females who suffered from HT were diagnosed with UEI. The serum level of IFN-γ and its gene expression showed a significant positive correlation with thyroid-stimulating hormone (TSH) and thyroid autoantibodies. However, a negative correlation was found with anti-müllerian hormone (AMH), free T4 (FT3), and free T4 (FT4). Analysis by linear regression revealed that TSH and FT3 were associated with serum level of IFN-γ; while FT3 was associated with IFN-γ gene expression. We concluded that both are valued markers in diagnosing UEI in female patients suffering from HT.


Icing and multilayering technique of injectable hydroxyapatite cement paste for cranial base reconstruction after transsphenoidal surgery: technical note.
Injectable hydroxyapatite cement (HAC, Biopex; Mitsubishi Pharma Corp., Osaka, Japan) can reconstruct the accurate contour of bone defects intraoperatively, and it is slowly replaced with bone by a process of resorption and osteoconduction, making it a useful substrate for the repair of cranial defects. In the operative site with continuous oozing of the cerebrospinal fluid, however, the implanted HAC may be dissolved and washed out as a result of its water solubility during the setting time. For successful reconstruction of cranial defects in such wet situations, we describe a new technique to reinforce the implanted HAC with a multilayered application. As a preliminary experiment, we observed that the setting process of the HAC was severely restricted by the environmental temperature. At a temperature of 5 degrees C, the initial setting time of the HAC could be extended to 10 hours after the beginning of the mixing of the HAC. Bone defects of the sellar floor after transsphenoidal surgery for pituitary adenomas, craniopharyngiomas, meningiomas, or suprasellar arachnoid cysts were reconstructed using the HAC in 55 patients during a 5-year period. The results and complications were obtained through retrospective review. Ninety-eight percent of bone defects were successfully repaired using the HAC, and the reconstruction remained stable over the course of this study. There was one case of postoperative cerebrospinal fluid leakage. Wound infection occurred in one patient, which required reoperation and removal of the biomaterial. The icing and multilayering method for proper use of this biomaterial resulted in restoration of the integrity of the cranial base bone and a decrease of cerebrospinal fluid leakage as a postoperative complication of transsphenoidal surgery. HAC is a biomaterial that is recommended to be used as the primary method for reconstructing cranial base bone defects.


Fulminant myocarditis and pulmonary cavity lesion induced by disseminated mucormycosis in a chronic hemodialysis patient: Report of an autopsied case.
Mucormycosis is a rare fungal infection occurring in the immunocompromised host. It is difficult to diagnose, and its cardiac involvement is extremely rare. Here, we report a 64-year-old Japanese man with a 5-year history of hemodialysis with disseminated mucormycosis causing fulminant myocarditis and pulmonary necrosis under glucocorticoid use. Two months before, he had received an implantable cardioverter defibrillator and started to take amiodarone for recurrent ventricular arrhythmias due to hypertensive cardiomyopathy. He developed amiodarone-induced interstitial pneumonia and then received glucocorticoid therapy. Although the interstitial pneumonia partially improved, a lung cavitary lesion developed in the upper right lobe. Antibiotics had no effect, and serologic tests, blood and sputum cultures and bronchoalveolar lavage fluid were all negative for infectious pathogens. Eventually, he died of fulminant myocarditis. Autopsy revealed disseminated mucormycosis with vascular invasion and fungal thrombi, hemorrhage and infarction in lung (cavity lesion), heart (severe myocarditis), brain, thyroid and subcutaneous tissue around the implantable cardioverter defibrillator. The lung cavitary lesion was the only clinical finding suggestive of mucormycosis before autopsy. When an immunocompromised patient shows a progressive lung cavity lesion, the possibility of mucormycosis should be considered so that a broad-spectrum antifungal agent can be empirically administered in a timely fashion.


A dynamic simulation of a two-phase anaerobic digestion system for solid wastes.
In this article, a two-phase system for the digestion of wastes with a high solid content is simulated. The solids are charged to the hydrolyzer and then leachate recirculation is activated until biodegradation is nearly complete. Several parameters are tested, namely moisture, leachate recirculation flow rate, and hydrolyzer-methanizer volume ratio. The results show that recirculation rate is an important parameter subject to optimization, with optimal values corresponding to hydrolyzer hydraulic retention times below 1 day. The quantity of recirculating water must be the highest possible. As a consequence, the organic load to the methanizer is reduced, making thus possible the use of a smaller methanizer volume.


Aflatoxin B1 Induces Reactive Oxygen Species-Mediated Autophagy and Extracellular Trap Formation in Macrophages.
Aflatoxins are a group of highly toxic mycotoxins with high carcinogenicity that are commonly found in foods. Aflatoxin B1 (AFB1) is the most toxic member of the aflatoxin family. A recent study reported that AFB1 can induce autophagy, but whether AFB1 can induce extracellular traps (ETs) and the relationships among innate immune responses, reactive oxygen species (ROS), and autophagy and the ETs induced by AFB1 remain unknown. Here, we demonstrated that AFB1 induced a complete autophagic process in macrophages (MΦ) (THP-1 cells and RAW264.7 cells). In addition, AFB1 induced the generation of MΦ ETs (METs) in a dose-dependent manner. In particular, the formation of METs significantly reduced the AFB1 content. Further analysis using specific inhibitors showed that the inhibition of either autophagy or ROS prevented MET formation caused by AFB1, indicating that autophagy and ROS were required for AFB1-induced MET formation. The inhibition of ROS prevented autophagy, indicating that ROS generation occurred upstream of AFB1-induced autophagy. Taken together, these data suggest that AFB1 induces ROS-mediated autophagy and ETs formation and an M1 phenotype in MΦ.


Acephaly: further evidence for disruption but not for amniotic bands.
Complete absence of the fetal head in singleton pregnancies is a very rare defect; to our knowledge there are only 7 reported cases. Decapitation by amniotic bands has been considered as the most probable cause. However, in none of the described cases except one were amniotic bands, constriction rings, or other related findings observed, raising the possibility that mechanisms other than amputation by amniotic bands are involved. We present a further case of acephaly and discuss the role of amniotic bands and alternative mechanisms of decapitation and a possible sequence of events leading to acephaly.


The Acomys cahirinus (spiny mouse) as a new model for biological and neurobehavioural studies.
Acomys cahirinus is a precocial murid and a comparison of its development with altricial species of the same family, such as the rat and mouse, may shed some light on the relationship between genetic and environmental factors in the development. The use of Acomys in neurobehavioural studies and its comparison with mouse and rat may be particularly profitable. Behavioural, differences particularly in the exploratory behaviour, are paralleled by differences in the brain anatomy. Therefore Acomys seems to be a new very promising tool for investigating neurological and behavioural developmental systems.


Th1/Th2/Th17‑related cytokines in the bronchoalveolar lavage fluid of patients with sarcoidosis: association with smoking.
Sarcoidosis is a multiorgan granulomatous disease of unknown etiology. The predominance of Th1‑related cytokines is observed in the bronchoalveolar fluid (BALF) in pulmonary sarcoidosis. Recently, Th17 cells have been postulated to be involved in the pathogenesis of sarcoidosis. Sarcoidosis is more prevalent in nonsmokers than in smokers. The exact effect of smoking on granulomatous inflammation in this disease remains unclear. The aim of the study was to evaluate the Th1/Th2/Th17‑related cytokine concentration in the BALF of patients with pulmonary sarcoidosis in relation to smoking status. The study included 74 patients with confirmed pulmonary sarcoidosis. Data on smoking status were available for 61 patients (26 ever‑smokers, 35 never‑smokers; mean 11 ±9.1 pack-years in smokers). The concentrations of interleukin (IL) 17A (IL‑17A), IL‑10, IL‑6, IL‑4, and IL‑2 as well as interferon γ (IFN‑γ) and tumor necrosis factor α (TNF‑α) were measured in BALF supernatants using a flow cytometry method--the Cytometric Bead Array. The median concentration of IL‑6, IFN‑γ, and IL‑17A (2.19 pg/ml, 1.28 pg/ml, and 6.08 pg/ml, respectively) did not differ significantly between smokers and nonsmokers. TNF‑α, IL‑10, IL‑4 and IL‑2 levels were below the detection limit in most patients. We observed a significant correlation between IFN‑γ concentration and the number of macrophages in BALF (r = 0.66, P <0.05) and between IL‑17A and IL‑6 levels (r = 0.94, P <0.05). We confirmed a significant role of IL‑6, IFN‑γ, and IL-17A in the local inflammatory response in sarcoidosis. However, the interpretation of the limited number of cytokine measurements should be made with caution. Further studies are needed to explain the effect of smoking on the pathomechanism of inflammation in sarcoidosis.


Pretreatment-assisted robot intrathoracic layered anastomosis: our exploration in Ivor-Lewis esophagectomy.
Minimal invasive Ivor-Lewis esophagectomy (MIIVE) with intrathoracic esophago-gastric anastomosis (EGA) is still under exploration and the preferred technique for intrathoracic anastomosis has not been established. We retrospectively reviewed 43 consecutive patients who underwent MIIVE using the series technique called pretreatment-assisted robot intrathoracic layered anastomosis (PRILA), performed by a single surgeon between September 2018 and December 2020. The operative outcomes were analyzed. The mean total operation time had been reduced from 446.38±54.775 minutes (range, 354-552) in the first year to 347.70±60.420 minutes (range, 249-450) later. There were no conversions to thoracotomy. All the patients achieved R0 resection. No patient suffered from anastomotic leakage. There was no 30-day mortality. The median length of postoperative stay was 10.0 days. PRILA further visualizes and streamlines the process of minimal invasive intrathoracic EGA, thus ensuring the precise anastomosis. It could be considered as a feasible alternative for intrathoracic EGA in MIILE.


A Multiphase Semistatic Training Method for Swarm Confrontation Using Multiagent Deep Reinforcement Learning.
In this paper, we propose a multiphase semistatic training method for swarm confrontation using multi-agent deep reinforcement learning. In particular, we build a swarm confrontation game, the 3V3 tank fight, based on the Unity platform and train the agents by a MDRL algorithm called MA-POCA, coming with the ML-Agent toolkit. By multiphase learning, we split the traditional single training phase into multiple consecutive training phases, where the performance level of the strong team for each phase increases in an incremental way. On the other hand, by semistatic learning, the strong team in all phases will stop learning when fighting against the weak team, which reduces the possibility that the weak team keeps being defeated and learns nothing at all. Comprehensive experiments prove that, in contrast to the traditional single-phase training method, the multiphase semistatic training method proposed in this paper can significantly increase the training efficiency, shedding lights on how the weak could learn from the strong with less time and computational cost.


Contractility and calcium signaling of human myometrium are profoundly affected by cholesterol manipulation: implications for labor?
The authors elucidate cholesterol's effect on human uterine contractility and calcium signaling to test the hypotheses that elevation of cholesterol decreases uterine activity and that oxytocin cannot augment contraction when cholesterol is elevated. The effects of cholesterol extraction with methyl beta-cyclodextrin and enrichment with low-density lipoproteins and cholesterol on contractile activity and intracellular calcium signaling in spontaneous or oxytocin-stimulated myometrium are determined. Force occurring spontaneously and with oxytocin is significantly increased by cholesterol extraction. Cholesterol enrichment profoundly inhibits force production in a dose-dependent manner and could reverse the effects of cholesterol extraction. Qualitatively similar results are found for nonpregnant and pregnant laboring and non-laboring myometrium. These contractile changes are related to changes in intracellular Ca2+ . Thus, elevated cholesterol is deleterious to contractility and Ca2+ signaling in human myometrium. Cholesterol may contribute to uterine quiescence but could cause difficulties in labor in obese/dyslipidemic women, consistent with their increased cesarean delivery rates.


The Ethiopian initiative to build sustainable capacity for operational research: overview and lessons learned.
Programme-based operational research is instrumental for the enhancement of tuberculosis (TB) control. In 2012, the Ethiopian Federal Ministry of Health launched an initiative for capacity building in operational research (OR). To develop sustainable capacity for OR in Ethiopia in a multiyear initiative. The initiative was developed in collaboration with regional, national and international experts. Teams representing regions in Ethiopia conducted OR addressing national and regional priorities. To make use of local expertise and increase sustainability, a domestic mentor training programme was included. Existing capacity was enhanced through a competitive grant scheme providing TB researchers with financial and technical support. The Ethiopian Tuberculosis Research Advisory Committee was also supported in its functions. Regional ethics review bodies were strengthened or established where they did not exist. Fifty-two people were trained and conducted 13 OR projects, of which six have been published to date. In addition, eight protocols were supported through grants. Ethics review bodies were strengthened in all regions. The initiative trained participants from all regions and succeeded in the completion of all stages of the OR process. The success of the programme can be attributed to the team approach, 'learning while doing', integrated mentorship programme and strong national ownership.


[Continuous midazolam infusion for refractory nonconvulsive status epilepticus in children].
We examined efficacy of continuous midazolam (MDL) infusion in seven episodes of refractory nonconvulsive status epilepticus (NCSE) in five children. Diagnosis included Lennox-Gastaut syndrome (two cases), and symptomatic generalized epilepsy, ring chromosome 20 syndrome, and epilepsy with continuous spike-waves during slow-wave sleep (one case each). One patient with Lennox-Gastaut syndrome and another with ring chromosome 20 syndrome had two episodes of NCSE. MDL was given as an initial bolus of 0.15 to 0.3 mg/kg, followed by continuous intravenous infusion at 0.1 to 0.2 mg/kg/hr. The infusion rate was increased slowly by 0.1 mg/kg/hr every 0.5 to 1.0 hr, up to 0.4 mg/kg/hr or until NCSE was controlled. The electroencephalogram, vital signs, blood pressure, and oxygen saturation were monitored during therapy. Electrical status epilepticus was abolished within a few hours in five of the seven episodes, and two patients could maintain wakefulness, oral intake, and bowel and bladder control throughout the continuous infusion. In one patient in whom NCSE recurred, it then remained uncontrolled even at a maximum dose. Serious complications such as respiratory depression or hypotension were not observed. Continuous intravenous infusion of MDL was effective and safe for NCSE in children, and can be used as firstline therapy for this condition.


The IADPSG diagnostic criteria identify women with increased risk of adverse pregnancy outcomes in Victoria.
Controversy remains surrounding International Association of Diabetes and Pregnancy Study Group (IADPSG) diagnostic criteria for gestational diabetes mellitus (GDM), including perceived improvement in perinatal outcomes and health service implications. We compared perinatal outcomes for untreated women meeting IADPSG-only criteria and women without GDM in Victoria. Women meeting IADPSG-only criteria were characterised according to fasting and one hour glucose thresholds and by region of birth. IADPSG criteria identified women with increased risk of adverse perinatal outcomes, particularly women born in Australia compared to Asian regions.


Advances in cosmetic micropigmentation.
Cosmetic micropigmentation for implanting pigments into the skin is a relatively new and beneficial procedure. We have found patient satisfaction to be high and complication rate low. We do stress that the help of an aesthetician is necessary in determining the color of pigmentation.


Differential pharmacology and clinical utility of rolapitant in chemotherapy-induced nausea and vomiting.
Chemotherapy-induced nausea and vomiting (CINV) is a debilitating side effect of many cytotoxic chemotherapy regimens. CINV typically manifests during two well-defined time periods (acute and delayed phases). The acute phase is the first 24 hours after chemotherapy and is largely managed with 5-hydroxytryptamine 3 receptor antagonists. The delayed phase, a 5-day at-risk period during which patients are not often in direct contact with their health care provider, remains a significant unmet medical need. Neurokinin-1 (NK-1) receptor antagonists have demonstrated protection against acute and delayed CINV in patients treated with highly emetogenic chemotherapy and moderately emetogenic chemotherapy when used in combination with a 5-hydroxytryptamine 3 receptor antagonist and dexamethasone. Furthermore, recent data indicate that this protection is maintained over multiple treatment cycles. Rolapitant, a selective and long-acting NK-1 receptor antagonist, is approved as oral formulation for the prevention of delayed CINV in adults. This review discusses the differential pharmacology and clinical utility of rolapitant in preventing CINV compared with other NK-1 receptor antagonists.


Reproducible polypeptide folding and structure prediction using molecular dynamics simulations.
The folding of a polypeptide from an extended state to a well-defined conformation is studied using microsecond classical molecular dynamics (MD) simulations and replica exchange molecular dynamics (REMD) simulations in explicit solvent and in vacuo. It is shown that the solvated peptide folds many times in the REMD simulations but only a few times in the conventional simulations. From the folding events in the classical simulations we estimate an approximate folding time of 1-2 micros. The REMD simulations allow enough sampling to deduce a detailed Gibbs free energy landscape in three dimensions. The global minimum of the energy landscape corresponds to the native state of the peptide as determined previously by nuclear magnetic resonance (NMR) experiments. Starting from an extended state it takes about 50 ns before the native structure appears in the REMD simulations, about an order of magnitude faster than conventional MD. The calculated melting curve is in good qualitative agreement with experiment. In vacuo, the peptide collapses rapidly to a conformation that is substantially different from the native state in solvent.


Predictors of fatigue and persistent fatigue in early rheumatoid arthritis: a longitudinal observational study, data from the ESPOIR cohort.
To determine, in a cohort of patients with early rheumatoid arthritis (RA), factors associated with fatigue at baseline, describe its evolution over 5 years of follow-up, and determine baseline predictors of persistent fatigue. We selected patients fulfilling the 2010 American College of Rheumatology/European League Against Rheumatism criteria for RA included in the ESPOIR cohort. Using bivariable and multivariable logistic regression models, we examined baseline variables associated with baseline fatigue (defined by visual analogue scale fatigue > 20) and baseline predictors of persistent fatigue (if the patient experienced fatigue at all visits during the 5 year follow-up period). We analysed 673 patients; 80.7% reported fatigue at baseline. At baseline, fatigue was associated with female gender, younger age, greater severity of morning stiffness, sleep problems, higher Health Assessment Questionnaire levels, presence of sicca symptoms, history of thyroid problems, and presence of psychological distress (depressive or anxiety symptoms). At 5 years of follow-up, the percentage of fatigued patients who reported fatigue at all time-points since baseline was 24.6% (referred to as 'persistent fatigue'). Independent baseline predictors were presence of sicca symptoms, greater severity of morning stiffness, and psychological distress. Fatigue is a frequent symptom in RA. The presence of sicca symptoms, greater severity of morning stiffness, and presence of psychological distress at baseline were associated with baseline fatigue and persistent fatigue at 5 years. We did not observe any association between baseline fatigue or persistent fatigue and the Disease Activity Score based on 28-joint count-erythrocyte sedimentation rate.


Hypotensive effects of 5-HT1A receptor agonists on the ventrolateral medullary pressor area in dogs.
An attempt to determine the central site of the sympathoinhibitory effects of 8-hydroxy-2-(di-n-propyl-amino)tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, has been made in normotensive anesthetized dogs. Intravenous and central (cisterna magna, vertebral artery) administration of 8-OH-DPAT induced dose-dependent decreases in blood pressure and sympathetic (splanchnic and renal) nerve activity in intact and baroreceptor denervated dogs. In contrast, 8-OH-DPAT was ineffective when injected into the nucleus tractus solitarii or into the raphe nuclei. Administration of 8-OH-DPAT into the ventrolateral pressor area (VLPA) decreased blood pressure and renal sympathetic nerve activity. The sympathoinhibitory effects of 8-OH-DPAT injected into the vertebral artery (v.a.) were antagonized by methiothepin and (+/-)pindolol injected into the v.a. Likewise, the effects of 8-OH-DPAT administered into the VLPA were antagonized by methiothepin injected into the same site. Depletion of central catecholamines and 5-HT content did not change the sympathoinhibitory effects of 8-OH-DPAT. These results suggested that 8-OH-DPAT has a direct effect on 5-HT1A receptors located in the VLPA in dogs.


Suppression of puerperal lactation by terguride. A double-blind study.
Clinical efficacy, prolactin (PRL)-lowering effect and tolerance of terguride (an 8-alpha-ergoline derived from Lisuride which acts as a partial dopaminergic agonist) were investigated in a double-blind study on inhibition of puerperal lactation using three different daily doses of the drug (0.25, 0.5 and 1.0 mg). With 0.5 and 1.0 daily therapeutical regimens PRL levels were suppressed in a dose-dependent manner and lactation was prevented. Terguride was highly well tolerated.


Phase separation of passive particles in active liquids.
The transport properties of colloidal particles in active liquids have been studied extensively. It has led to a deeper understanding of the interactions between passive and active particles. However, the phase behavior of colloidal particles in active media has received little attention. Here, we present a combined experimental and numerical investigation of passive colloids dispersed in suspensions of active particles. Our study reveals dynamic clustering of colloids in active media due to an interplay of activity and attractive effective potential between the colloids. The strength of the effective potential is set by the size ratio of passive particles to the active ones. As the relative size of the passive particles increases, the effective potential becomes stronger and the average size of the clusters grows. The simulations reveal a macroscopic phase separation at sufficiently large size ratios. We will discuss the effect of density fluctuations of active particles on the nature of effective interactions between passive ones.


[Chemical constituents from Coptis chinensis].
To study the chemical constituents of Coptis chinensis. The compounds were separated and purified by column chromatography and their structures were identified by spectroscopic methods. Seven compounds were isolated from the chloroform extract of Coptis chinensis, whose structures were determined as worenine (1),8,9-dihydroxy-1,5,6, 10b-tetrahydro-2H-pyrrolo[2,1 -alpha] isoquinolin-3-one (2),(+/-) -5,5'-dimethoxy-lariciresinol (3),3,4-dihydroxy-phenylethylalcohol(4), methyl-5-O-feruloylquinate (5), ethyl-5-O- feruloylquinate (6), apocynol (7). Compounds (3) is isolated from this genus for the first time, compounds (5), (6), (7) are isolated from this plant for the first time.


Effect of simulated intraoral variables on the accuracy of a photogrammetric imaging technique for complete-arch implant prostheses.
Conventional impression techniques to obtain a definitive cast for a complete-arch implant-supported prosthesis are technique-sensitive and time-consuming. Direct optical recording with a camera could offer an alternative to conventional impression making. The purpose of this in vitro study was to test a novel intraoral image capture protocol to obtain 3-dimensional (3D) implant spatial measurement data under simulated oral conditions of vertical opening and lip retraction. A mannequin was assembled simulating the intraoral conditions of a patient having an edentulous mandible with 5 interforaminal implants. Simulated mouth openings with 2 interincisal openings (35 mm and 55 mm) and 3 lip retractions (55 mm, 75 mm, and 85 mm) were evaluated to record the implant positions. The 3D spatial orientations of implant replicas embedded in the reference model were measured using a coordinate measuring machine (CMM) (control). Five definitive casts were made with a splinted conventional impression technique of the reference model. The positions of the implant replicas for each of the 5 casts were measured with a Nobel Procera Scanner (conventional digital method). For the prototype, optical targets were secured to the implant replicas, and 3 sets of 12 images each were recorded for the photogrammetric process of 6 groups of retractions and openings using a digital camera and a standardized image capture protocol. Dimensional data were imported into photogrammetry software (photogrammetry method). The calculated and/or measured precision and accuracy of the implant positions in 3D space for the 6 groups were compared with 1-way ANOVA with an F-test (α=.05). The precision (standard error [SE] of measurement) for CMM was 3.9 μm (95% confidence interval [CI] 2.7 to 7.1 μm). For the conventional impression method, the SE of measurement was 17.2 μm (95% CI 10.3 to 49.4 μm). For photogrammetry, a grand mean was calculated for groups MinR-AvgO, MinR-MaxO, AvgR-AvgO, and MaxR-AvgO obtaining a value of 26.8 μm (95% CI 18.1 to 51.4 μm). The overall linear measurement error for accurately locating the top center points (TCP) followed a similar pattern as for precision. CMM (coordinate measurement machine) measurement represents the nonclinical gold standard, with an average error TCP distance of 4.6 μm (95% CI 3.5 to 6 μm). All photogrammetry groups presented an accuracy that ranged from 63 μm (SD 17.6) to 47 μm (SD 9.2). The grand mean of accuracy was calculated as 55.2 μm (95% CI 8.8 to 130.8 μm). The CMM group (control) demonstrated the highest levels of accuracy and precision. Most of the groups with the photogrammetric method were statistically similar to the conventional group except for groups AvgR-MaxO and MaxR-MaxO, which represented maximum opening with average retraction and maximum opening with maximum retraction.


Attractylone attenuates sepsis-associated encephalopathy and cognitive dysfunction by inhibiting microglial activation and neuroinflammation.
Multiple studies demonstrated that sepsis is a life-threatening state of organ dysfunction caused by infection and can induce neuroinflammation and cognitive impairment. The aim of this study was to evaluate the protective effects of attractylone (Atr) on sepsis-associated encephalopathy (SAE) and cognitive dysfunction. Moreover, we studied the underlying molecular mechanisms. We used an LPS-induced sepsis mouse model and evaluated the cognitive function with the Morris water maze and open field test. Neuronal damage in the hippocampus was assessed by immunohistochemical analysis. BV2 cells were used to identify the protective mechanism of Atr. The result showed that Atr attenuated LPS-induced cognitive impairment, neural apoptosis, inflammatory factors, and microglial activation. The in vitro experiment showed that Atr promoted silent information regulator 1 (SIRT1) expression and suppressed NFκB expression. Downregulation of SIRT1 reversed the protective effect of Atr in the LPS condition. Moreover, Atr-induced SIRT1 expression promoted BV2 from LPS-induced M1 to M2 phenotype. Taken together, these results indicated that Atr was a potential therapeutic agent for SAE and cognitive dysfunction.


Role of Macrophages in the Pathogenesis of Genotype VII Newcastle Disease Virus in Chickens.
Long-term evolution of Newcastle disease virus (NDV) results in substantial alteration in viral pathogenesis. NDVs of genotype VII, a late genotype, show marked tropism to lymphoid tissues, especially to macrophages in chickens. However, the role of macrophages in the pathogenesis of genotype VII NDV is still unclear. Herein, NDV infectivity in macrophages and the role of macrophages in the pathogenesis of genotype VII NDV in chickens were investigated. We reported that NDV strains of genotype VII (JS5/05) and IV (Herts/33) can replicate in the adherent (predominantly macrophages) and non-adherent cells (predominantly lymphocytes) derived from chicken peripheral blood mononuclear cells (PBMCs), and significantly higher virus gene copy was detected in the adherent cells. In addition, JS5/05 had significantly higher infectivity in PBMC-derived adherent cells than Herts/33, correlating with its enhanced tropism to macrophages in the spleen of chickens. Interestingly, the depletion of 68% of macrophages exerted no significant impact on clinical signs, mortality and the systematic replication of JS5/05 in chickens, which may be associated with the contribution of non-depleted macrophages and other virus-supportive cells to virus replication. Macrophage depletion resulted in a marked exacerbation of tissue damage and apoptosis in the spleen caused by JS5/05. These findings indicated that macrophages play a critical role in alleviating tissue damage caused by genotype VII NDV in chickens. Our results unveiled new roles of macrophages in NDV pathogenesis in chickens.


Anatomical variations in the branches of the human aortic arch: a recent study of a South Australian population.
Variations of the branches of the aortic arch are likely to occur as a result of the altered development of certain branchial arch arteries during the embryonic period of gestation. In the present investigation the pattern of branches of the aortic arch was studied in 81 cadavers from a recent South Australian population of European descent, who have migrated to (n = 38) or were born and lived in (n = 43) South Australia during the twentieth century. Two principal variations were noted in the present study. Firstly, in 6 cadavers, the left vertebral artery originated directly from the arch of the aorta, between the left common carotid and the left subclavian arteries. The 6 subjects were among the subgroup born in South Australia, giving an incidence of 13.95%, which is much higher than in previous reports. The overall incidence of 7.41%, when related to the whole group, is also higher than incidences reported in other populations. The presence of this variation suggests that in some individuals part of the aortic arch is formed from the left 7(th) inter-segmental artery. Secondly, none of the cadavers examined had the thyroidea ima artery, contrasting with previously reported incidences that varied between 4% and 10%. Since all 6 cadavers with the left vertebral artery variant were born in South Australia, it is suggested that environmental factors may have contributed to this variation. Significant environmental changes in South Australia around the turn of the twentieth century are discussed. This study represents the first systematic investigation of the branches of the aortic arch in a South Australian population and provides data relevant to the practice of medicine.


Prevalence of Mycobacterium avium subsp. paratuberculosis in farmed red deer (Cervus elaphus) with grossly normal mesenteric lymph nodes.
To estimate the prevalence of Mycobacterium avium subsp. paratuberculosis (Map) in farmed deer with no gross post-mortem evidence of Map infection slaughtered in New Zealand, and to assess predictors of infection. Mesenteric lymph node (MLN) samples (n = 251) were collected from 60 lines of deer presented at two slaughterhouses in the North and two in the South Island of New Zealand between October 2008 and January 2009 and cultured for Map. Estimates of individual animal prevalence for each island were adjusted to account for the clustering of individual observations within herds. The national herd prevalence estimate was calculated as a weighted mean, with weights being the proportion of herds from which deer were slaughtered at North and South Island slaughterhouses among all herds slaughtering deer throughout New Zealand. Age, gender, and the presence of other carcasses with enlarged and/or granulomatous MLN in the same line (line status) were assessed as predictors of infection using multivariable logistic regression. A national cluster-adjusted individual animal prevalence of 45 (95% CI = 30-60)% was estimated, with North and South Island prevalences of 29 (95% CI = 16-45)% and 51 (95% CI = 36-66)%, respectively. Line status was a strong predictor of infection in young deer (OR 7.1, 95% CI = 2.4-21.5), but not in older deer. Herd-level prevalence was 44 (95% CI = 24-64)% in the North Island and 67 (95% CI = 49-85)% in the South Island. Weighted adjustment resulted in a national herd-level prevalence estimate of 59 (95% CI = 41-78)%. This study has provided a national baseline prevalence estimate for Map infection at the individual and herd-level, showing a contrast between the North and South Islands. More research to investigate the factors contributing to the difference in infection prevalence seen between the islands may help to identify suitable control measures for Map in deer herds.


The spread of apoptosis through gap-junctional channels in BHK cells transfected with Cx32.
Programmed cell death (apoptosis) occurs both during normal development and as a result of various pathological conditions. An in vitro system was used to explore the transmission of death signals from apoptotic cells to cells with which they were coupled via gap junctions. Confluent cultures of baby hamster kidney (BHK) cells, stably transfected with the gap-junctional protein connexin32, were scrape loaded with cytochrome C (cyC), a mitochondria-derived apoptotic agent, to introduce the protein into cells injured by the cut. The cultures were subsequently analyzed for the presence of activated caspases, the distribution of TUNEL staining, and the binding of annexin V. Although cyC is too large to traverse the gap junctional channel, each of the assays revealed that apoptosis had spread from dying cells at the margin of the scrape to otherwise healthy neighboring cells to which they were coupled. This "bystander effect" was significantly reduced in the presence of agents that block gap junctional intercellular communication.


Chronic Abdominal Pain: A Case of Giant Fecalith in the Distal Jejunum.
A fecalith is a mass of an accumulation of hardened fecal matter that is seen in patients with Chagas disease, Hirschsprung's disease, and inflammatory bowel disease. In this article, we report a case of a 53-year-old female with chronic abdominal pain who was admitted with progressive weight loss, near syncope episode, and serum potassium of 2.6 mg/dL. An abdominal computed tomography (CT) scan revealed a left lower quadrant complex mass measuring 10.3 cm, with asymmetrical wall thickening and inflammatory stranding, non-discarding the compromise of the small bowel and consequent mild small bowel distention. A fecalith of 10.3 x 10.9 x 8.7 cm was found during an exploratory laparotomy in the small intestine. We report this rare case of distal jejunum fecalith accompanied by chronic pain.


Effect of lysophosphatidylglycerol on intracellular free Ca2+ concentration in A10 vascular smooth muscle cells.
Although plasma levels of lysophosphatidylglycerol (LPG) are increased in hypertension, its role in the pathogenesis of vascular defects is not clear. In view of the importance of Ca2+ overload in causing vascular smooth muscle (VSM) dysfunction, the action of LPG on [Ca2+]i in cultured A10 VSM cell line was examined by using Fura 2-AM acetoxymethyl ester technique. LPG was found to induce a concentration-dependent increase in [Ca2+]i in VSM cells. This change was dependent both on the extracellular and intracellular Ca2+ sources, as it was reduced by 30% by EGTA, an extracellular Ca2+ chelator, and 70% by thapsigargin, a sarcoplasmic reticulum (SR) Ca2+-pump inhibitor. However the increase in [Ca2+]i due to LPG was not altered by caffeine or ryanodine, which affect Ca2+-release through the ryanodine receptors in the SR. On the other hand, LPG-induced change in [Ca2+]i was suppressed by 2-nitro-4-carboxyphenyl N,N-diphenylcarbamate, a phospholipase C (PLC) inhibitor, as well as by xestospongin and 2-aminoethoxydiphenyl borate, two inositol trisphosphate (IP3) receptor inhibitors in the SR. These observations support the view that LPG-induced increase in [Ca2+]i in VSM cells is mainly a result of Ca2+ release from Ca2+ pool in the SR through PLC/IP3-sensitive signal transduction mechanism. Furthermore, it is suggested that the elevated level of LPG may induce intracellular Ca2+ overload and thus play a critical role in the development of vascular abnormalities.


Metronomic administration of lomustine following palliative radiation therapy for appendicular osteosarcoma in dogs.
The purpose of this study was to determine if metronomic administration of lomustine following palliative radiation therapy (RT) improved length of palliation and therefore survival in dogs with appendicular osteosarcoma compared to treatment with palliative radiation alone. A search of medical records identified dogs with appendicular osteosarcoma, treated with palliative RT (2 fractions of 8 Gray in a 24 hour time frame, day 0 and day 1; or day 0, 6 hours apart). Data collected included signalment, history, clinical signs, physical examination findings, clinicopathologic abnormalities, extent of disease, response, toxicity, other therapy, survival time, and whether dogs received metronomic lomustine (ML) or not. Of 86 patients, 43 received ML while 43 did not. Median survival time (MST) was not significantly different (P = 0.84), at 184 +/- 17 days for patients which received ML, and 154 +/- 20 days for those which did not. Metronomic lomustine administration was well-tolerated, but it did not improve survival in dogs with palliatively treated osteosarcoma.


The role of clinicopathologic and molecular prognostic factors in the post-mastectomy radiotherapy (PMRT): a retrospective analysis of 912 patients.
To assess the association of clinicopathologic and molecular features with loco-regional recurrence (LRR) in post-mastectomy breast cancer patients with or without adjuvant radiotherapy (PMRT). We retrospectively reviewed data of patients undergone to mastectomy followed or not by PMRT between January 2004 and June 2013. The patients were divided according to clinicopathologic and molecular sub-classification features. LRR and Cancer Specific Survival (CSS) were calculated using the Kaplan-Meier method; the prognostic factors were compared using long-rank tests and Cox regression model. A total of 912 patients underwent to mastectomy of whom 269 (29.5%) followed by PMRT and 643 (70.5%) not; among the PMRT group, 77 underwent to the chest wall (CW) and 202 to the chest wall and lymphatic drainage (CWLD) irradiation. The median follow-up was 54 months (range, 3-118). No significant difference in terms of LRR and CSS was found between non-PMRT and PMRT group (p=0.175; and p=0.628). The multivariate analysis of LRR for patients who did not undergo PMRT showed a significant correlation with the presence of extracapsular extension (ECE) (p=0.049), Ki-67>30% (p=0.048) and triple negative status (p=0.001). In the PMRT group, triple negative status resulted as the only variable significantly correlated to LRR (p=0.006) at the multivariate analysis and T-stage also showed a trend to significance (p=0.073). Finally, no difference in LRR control was shown between CW and CWLD-PMRT (p=0.078). After mastectomy ECE, a cut off of Ki-67>30% and triple negative status were strictly correlated with LRR regardless of clinicopathologic stage. PMRT has a positive impact in decreasing LRR in patients with this molecular profile. Besides, CW might represent a valid option for patients with one to three positive nodes.


High-throughput assay optimization and statistical interpolation of rubella-specific neutralizing antibody titers.
Rubella remains a social and economic burden due to the high incidence of congenital rubella syndrome (CRS) in some countries. For this reason, an accurate and efficient high-throughput measure of antibody response to vaccination is an important tool. In order to measure rubella-specific neutralizing antibodies in a large cohort of vaccinated individuals, a high-throughput immunocolorimetric system was developed. Statistical interpolation models were applied to the resulting titers to refine quantitative estimates of neutralizing antibody titers relative to the assayed neutralizing antibody dilutions. This assay, including the statistical methods developed, can be used to assess the neutralizing humoral immune response to rubella virus and may be adaptable for assessing the response to other viral vaccines and infectious agents.


Use of carotid plaque neovascularization at contrast-enhanced US to predict coronary events in patients with coronary artery disease.
To determine whether carotid plaque neovascularization as assessed with contrast-enhanced ultrasonography (US) can help predict future coronary events in patients with stable coronary artery disease (CAD). The study was approved by the hospital ethics committee, and informed consent was obtained from all patients. Three hundred twelve consecutive patients (228 men; mean age, 63 years ± 9; age range, 42-88 years) with both CAD and at least one carotid plaque thicker than 2.0 mm underwent both standard and contrast-enhanced carotid US. Patients with stable CAD were followed up for 8-47 months (mean, 33 months ± 9) or until a coronary event occurred. Statistical analysis was performed with the Student t test, χ(2) analysis, Kaplan-Meier method, and Cox proportional hazards regression models. Contrast material enhancement of plaque was seen in 42 of 51 patients (82%) with acute coronary syndrome (ACS) and 114 of 261 patients (43.7%) with stable CAD (P < .001). Coronary events occurred during the follow-up period in 24 of 111 patients (21.6%) with contrast material enhancement of plaque and only seven of 137 patients (5.1%) without enhancement (P< .001). In 248 patients with stable CAD and follow-up, Kaplan-Meier analysis demonstrated a significantly higher probability of developing coronary events in patients with contrast material enhancement of plaque than in those without contrast material enhancement (P < .001). The presence of contrast material enhancement of plaque was a significant and independent predictor of future coronary events in patients with stable CAD (odds ratio: 3.90; 95% confidence interval: 1.60, 9.46; P = .003). Contrast material enhancement of plaque is more common in patients with ACS than in those with stable CAD and is a significant and independent predictor of future coronary events in patients with stable CAD, suggesting that noninvasive contrast-enhanced carotid US may be used as a method for risk stratification of patients with stable CAD.


Predictors of functional capacity as measured by the Glittre activities of daily living test in women with rheumatoid arthritis.
Although pulmonary involvement is the most common extra-articular manifestation of rheumatoid arthritis (RA), traditional pulmonary function tests (PFTs) do not show a good correlation with the field tests usually performed in these patients. In recent decades, measurement of ventilation distribution heterogeneity through the nitrogen single-breath washout (N2SBW) test and evaluation of functional capacity during exercise using the Glittre activities of daily living test (GA-T) have been increasingly used. Therefore, the objective of this study was to evaluate predictors of GA-T outcomes in women with RA considering demographic, anthropometric, clinical, functional variables, and chest computed tomography (CT) findings. Forty-three women with RA underwent the GA-T, the N2SBW test, spirometry, measurement of the diffusing capacity for carbon monoxide (DLco), measurement of respiratory muscle strength, and evaluation of physical function of the lower and upper limbs through the Health Assessment Questionnaire Disability Index (HAQ-DI). Chest CT scans were analyzed retrospectively. The GA-T time showed significant correlations with the DLco (rs=-0.397, P=0.008), forced vital capacity/DLco (rs=0.307, P=0.044), phase III slope of the N2SBW test (SIIIN2, rs=0.644, P<0.0001), and the HAQ-DI (rs=0.482, P=0.001). Disease extent as assessed by chest CT was associated with the GA-T time. On multiple regression analysis, the SIIIN2 and HAQ-DI were the only predictors of the GA-T time, explaining 40% of its variability. Thus, ventilation distribution heterogeneity and worse physical function substantially explain the variability in GA-T time in women with RA and varying extents of disease on chest CT.


[Canadian Mental Health Law: recognizing and rectifying a problematic situation].
This article explores several conundrums and attempts to identify ways of redirecting the Canadian ship of state. It first presents an overview of some of the salient features of the array of mainly coercive provincial and territorial mental health statutes. The failure in the main of the Charter to deliver on its early ostensible promises for people with mental health problems is assessed. Next, the author argues that extant legislation remains anchored in the medical model, when other human rights promoting paradigms transforms the statutory agenda.


Moutan Cortex Protects Hepatocytes against Oxidative Injury through AMP-Activated Protein Kinase Pathway.
Moutan Cortex, the root bark of Paeonia suffruticosa ANDREWS in Ranunculaceae, has widely demonstrated analgesic, anti-spasmodic, and anti-inflammatory effects in various cancer and immune cell lines. Oxidative stress is associated with development of several diseases, including liver disease. We prepared the water extract of Moutan Cortex (MCE) to investigate the cytoprotective activities and its mechanism. MCE protected hepatocytes from arachidonic acid (AA)+iron induced oxidative stress, as indicated by reactive oxygen species (ROS) production and cell viability analysis. MCE also suppressed mitochondrial dysfunction in AA+iron-treated human hepatocyte-derived hepatocellular carcinoma cell line, HepG2 cells. In addition, MCE treatment induces AMP-activated protein kinase (AMPK) and liver kinase B1 phosphorylation, which play a role in inhibition of oxidative stress induced cell death. Moreover, one of the MCE compounds, chlorogenic acid, exerted protective effects against oxidative stress and apoptosis. Taken together, MCE protected hepatocytes against AA+iron-induced oxidative stress through AMPK activation, and may be a candidate for the treatment of liver disease.


Use of microarrays with different probe sizes for monitoring gene expression.
Microarrays with oligonucleotides of different lengths were used to monitor gene expression at a whole-genome level. To determine what length of oligonucleotide is a better alternative to PCR-generated probes, the performance of oligonucleotide probes was systematically compared to that of their PCR-generated counterparts for 96 genes from Shewanella oneidensis MR-1 in terms of overall signal intensity, numbers of genes detected, specificity, sensitivity, and differential gene expression under experimental conditions. Hybridizations conducted at 42 degrees C, 45 degrees C, 50 degrees C, and 60 degrees C indicated that good sensitivities were obtained at 45 degrees C for oligonucleotide probes in the presence of 50% formamide, under which conditions specific signals were detected by both PCR and oligonucleotide probes. Signal intensity increased as the length of the oligonucleotide probe increased, and the 70-mer oligonucleotide probes produced signal intensities similar to the intensities obtained with the PCR probes and detected numbers of open reading frames similar to the numbers detected with the PCR probes. PCR amplicon, 70-mer, 60-mer, and 50-mer arrays had detection sensitivities of 5.0, 25, 100, and 100 ng of genomic DNA, which were equivalent to approximately 1.9 x 10(6), 9.2 x 10(6), 3.7 x 10(7), and 3.7 x 10(7) copies, respectively, when the array was hybridized with genomic DNA. To evaluate differential gene expression under experimental conditions, S. oneidensis MR-1 cells were exposed to low- or high-pH conditions for 30 and 60 min, and the transcriptional profiles detected by oligonucleotide probes (50-mer, 60-mer, and 70-mer) were closely correlated with those detected by the PCR probes. The results demonstrated that 70-mer oligonucleotides can provide the performance most comparable to the performance obtained with PCR-generated probes.


Characteristics of drug-phospholipid coprecipitates I: Physical properties and dissolution behavior of griseofulvin-dimyristoylphosphatidylcholine systems.
Solid dispersions of griseofulvin and dimyristoylphosphatidylcholine (lecithin) have been prepared as both coprecipitates and physical mixtures, and their physical characteristics and dissolution behavior compared with pure griseofulvin. The dissolution of the physical mixtures was similar to pure drug, but the coprecipitates yielded a 3.5-fold greater initial dissolution rate and a limiting concentration after 60 min which was 72% greater at a griseofulvin-lecithin weight ratio of 19:1. Increasing the lecithin content to 1.5:1 compositions resulted in only a further 50% increase in the initial dissolution rate and a further 12% increase in the limiting concentration. The effect of the pH of the medium on dissolution was slight, but varied with the composition of the system. The phase diagram indicated that these systems have no significant eutectic or solid solution formation. X-ray diffraction spectra further showed that freshly prepared or aged coprecipitates contained griseofulvin crystals, and photomicrographs showed that the crystals essentially retained their characteristic shapes and sizes in all systems. Differential thermal analysis yielded heats of fusion that gave a good linear correlation with the percent of griseofulvin dissolved from coprecipitates at all time intervals, but not with physical mixtures. Furthermore, aged coprecipitates underwent a slower rate of dissolution compared with fresh samples. The results are interpreted to suggest that griseofulvin undergoes improved dissolution from coprecipitates due to the formation of crystals of lower stability. In addition, the rapid dispersion of lecithin in the aqueous medium (as seen microscopically) entraps griseofulvin in myelinic structures and liposomes and effectively increases the saturation concentration of drug in the diffusion layer during the dissolution process.


Enhanced transfection rates of small-interfering RNA using dioleylglutamide-based magnetic lipoplexes.
Magnetic force-guided delivery (magnetofection) has been studied as a new modality for introducing small-interfering RNA (siRNA) into target cells, but its delivery efficiency needs to be improved. Here, we report that magnetofection of N,N''-dioleylglutamide (DG)-based magnetic lipoplexes can substantially enhance the cellular delivery rates of siRNA. The siRNA was triply complexed with DG-based cationic liposomes and cationic iron-oxide nanoparticles. The formation of siRNA-containing magnetic lipoplexes was confirmed by gel retardation, sizes, and zeta potential values. Fluorescence microscopy and flow cytometry of fluorescent marker-labeled siRNA revealed that the DG-based magnetic lipoplexes conferred a higher cellular delivery rate of siRNA than DG-based lipoplexes or Lipofectamine 2000. In addition to the enhanced delivery of siRNA, the DG-based magnetic lipoplexes showed lack of cytotoxicity. We then tested the application of these magnetic lipoplexes for the cellular delivery of anticancer siRNA. Cancer cell lines magnetofected with DG-based magnetic lipoplexes containing Mcl1-specific siRNA (siMcl1) showed much lower viability than the groups treated with DG-based lipoplexes or Lipofectamine 2000, indicating that our magnetofection strategy conferred greater siMcl1-induced anticancer activity. These results suggest that DG-based magnetic lipoplexes are promising candidates for enhancing the efficiency of magnetic field-guided siRNA delivery.


[Enteric viruses and bacteriological parameters in molluscs].
Eighty-seven samples of shellfish were collected considering: type of mollusc, origin, growing area, monitoring or for human purpose. The bacteriological parameters were: Fecal Coliforms, Escherichia coli, and Salmonella; whereas the virological parameters included: Hepatitis A and E virus, Rotavirus, Astrovirus and Enterovirus. In total, 63.2% of samples had normal bacteria values, only one sample was Salmonella positive. The percentage of positive samples for Hepatitis A virus was 5.7%, Rotavirus 29.9%, Astrovirus 27.6%, Enterovirus 10.3%. The recovery of hepatitis E virus was always negative, whereas 13 samples (14.9%) were positive for two viruses.


Working at the intersection of context, culture, and technology: Provider perspectives on antimicrobial stewardship in the emergency department using electronic health record clinical decision support.
Antibiotic stewardship programs (ASPs) have not been fully developed for the emergency department (ED), in part the result of the barriers characteristic of this setting. Electronic health record-based clinical decision support (EHR CDS) represents a promising strategy to implement ASPs in the ED. We aimed to determine the cultural beliefs and structural barriers and facilitators to implementation of antimicrobial stewardship in the pediatric ED using EHR CDS. Interviews and focus groups were conducted with hospital and ED leadership, attending ED physicians, nurse practitioners, physician assistants, and residents at a single health system in Colorado. We reviewed and coded the data using constant comparative analysis and framework analysis until a final set of themes emerged. Two dominant perceptions shaped providers' perspectives on ASPs in the ED and EHR CDS: (1) maintaining workflow efficiency and (2) constrained decision-making autonomy. Clinicians identified structural barriers to ASPs, such as pace of the ED, and various beliefs that shaped patterns of practice, including accommodating the prescribing decisions of other providers and managing parental expectations. Recommendations to enhance uptake focused on designing a simple yet flexible user interface, providing clinicians with performance data, and on-boarding clinicians to enhance buy-in. Developing a successful ED-based ASP using EHR CDS should attend to technologic needs, the institutional context, and the cultural beliefs of practice associated with providers' antibiotic prescribing.


Doxycycline in the treatment of respiratory tract infections. Results of a pan-European multi-centre trial.
In the winter of 1973-4, general practitioners from seven European countries took part in a multi-centre trial of doxycycline in the treatment of infections of the respiratory tract. The carefully designed protocol was observed by all participants. A total of 1,747 patients were admitted to the trial; their ages ranged from 6 years to over 80. The commonest diagnoses (50%) were acute bronchitis and acute exacerbations of chronic bronchitis. On the recommended dosage of 200 mg doxycycline on the first day, followed by 100 mg daily thereafter (though 200 mg could be continued daily in severe cases), 87% of patients achieved good or very good results. Both subjective (pain) and objective (sputum volume and viscosity, temperature, cough) measures showed rapid improvement, usually by the third to fifth days. Side-effects were minimal and mainly gastrointestinal and caused only 4 patients to discontinue treatment. Overall, doxycycline proved its effectiveness and rapidity of action.


Time-of-day of blood-feeding: effects on mosquito life history and malaria transmission.
Biological rhythms allow organisms to compartmentalise and coordinate behaviours, physiologies, and cellular processes with the predictable daily rhythms of their environment. There is increasing recognition that the biological rhythms of mosquitoes that vector parasites are important for global health. For example, whether perturbations in blood foraging rhythms as a consequence of vector control measures can undermine disease control. To address this, we explore the impacts of altered timing of blood-feeding on mosquito life history traits and malaria transmission. We present three experiments in which Anopheles stephensi mosquitoes were fed in the morning or evening on blood that had different qualities, including: (i) chemical-induced or (ii) Plasmodium chabaudi infection-induced anaemia; (iii) Plasmodium berghei infection but no anaemia; or (iv) stemming from hosts at different times of day. We then compared whether time-of-day variation in blood meal characteristics influences mosquito fitness proxies relating to survival and reproduction, and malaria transmission proxies. Mosquito lifespan is not influenced by the time-of-day they received a blood meal, but several reproductive metrics are affected, depending on other blood characteristics. Overall, our data suggest that receiving a blood meal in the morning makes mosquitoes more likely to lay eggs, lay slightly sooner and have a larger clutch size. In keeping with previous work, P. berghei infection reduces mosquito lifespan and the likelihood of laying eggs, but time-of-day of blood-feeding does not impact upon these metrics nor on transmission of this parasite. The time-of-day of blood-feeding does not appear to have major consequences for mosquito fitness or transmission of asynchronous malaria species. If our results from a laboratory colony of mosquitoes living in benign conditions hold for wild mosquitoes, it suggests that mosquitoes have sufficient flexibility in their physiology to cope with changes in biting time induced by evading insecticide-treated bed nets. Future work should consider the impact of multiple feeding cycles and the abiotic stresses imposed by the need to forage for blood during times of day when hosts are not protected by bed nets.


Treatment of posterior pharyngeal wall carcinoma.
Thirty cases of posterior pharyngeal wall carcinoma (seen in the Emory University system between 1977 and 1982) are reviewed. The study was implemented to resolve the question, "Which therapeutic alternative is preferred for the treatment of the lesion--radiation or therapy?" From our clinical experience, a treatment plan of primary surgery with postoperative radiation appears to be preferred over a treatment plan of radiation for cure with surgery held for salvage. A current review of the literature on the treatment of posterior wall carcinoma will be presented along with a review of our series.


Bipolar co-morbidity in pediatric obsessive-compulsive disorder: clinical and treatment implications.
This paper reports on implications of bipolar disorder (BD) co-morbidity in 120 children and adolescents with obsessive-compulsive disorder (OCD) (84 males, 36 females, age 13.7 +/- 2.8 years), diagnosed using a clinical interview according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria, and naturalistically followed-up for 12 +/- 6 months. The aim of this naturalistic, retrospective study was to explore the effect of BD co-morbidity, disentangling it from other co-occurring variables, namely the co-morbidity with disruptive behavior disorders. Forty three patients (35.8%) had a bipolar co-morbidity. Compared with OCD patients without BD, they had an earlier onset of OCD, a greater severity and functional impairment, more frequent hoarding obsessions and compulsions, and a poorer response to treatments. They had a higher co-morbidity with attention-deficit/hyperactivity disorder (ADHD) and oppositional-defiant disorder (ODD), and a lower co-morbidity with generalized anxiety disorder (GAD). Finally, they received more mood stabilizers, and 30.2% of them did not receive serotonin-selective reuptake inhibitors (SSRIs) because of pharmacological (hypo)mania. When all the OCD responders and nonresponders were compared, nonresponders (n = 42, 35%) were more severe at baseline and at end of the follow-up, had more frequently hoarding obsessions and compulsions, and had more frequent BD, ODD, and conduct disorder (CD) and less GAD and panic disorder. In the final regression model, hoarding obsessions and compulsions, co-morbidity with ODD, and CD were negative predictors of treatment outcome. This study suggests that even though bipolar co-morbidity is frequent and affects phenomenology and co-morbidity in pediatric OCD, its effect on treatment response seems prevalently accounted for by co-morbidity with disruptive behavior disorders. The significance of the hoarding subtype deserves further research on larger samples of pediatric patients.


Citrus peel extract protects against diesel exhaust particle-induced chronic obstructive pulmonary disease-like lung lesions and oxidative stress.
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide and characterized by emphysema, small airway remodeling and mucus hypersecretion. Citrus peels have been widely used as food spices and in traditional Chinese medicine for chronic lung disease. Given that citrus peels are known for containing antioxidants and anti-inflammatory compounds, we hypothesize that citrus peel intake can suppress oxidative stress and inflammatory response to air pollution exposure, thereby alleviating COPD-like pathologies. This study aimed to investigate the efficacy of citrus peel extract, namely Guang Chenpi (GC), in preventing the development of COPD induced by diesel exhaust particles (DEPs) and its potential mechanism. DEP-induced COPD-like lung pathologies, inflammatory responses and oxidative stress with or without GC treatment were examined in vivo and in vitro. Our in vivo study showed that GC was effective in decreasing inflammatory cell counts and inflammatory mediator (IL-17A and TNF-α) concentrations in bronchoalveolar lavage fluid (BALF). Pretreatment with GC extract also significantly decreased oxidative stress in the serum and lung tissue of DEP-induced COPD rats. Furthermore, GC pretreatment effectively reduced goblet cell hyperplasia (PAS positive cells) and fibrosis of the small airways, decreased macrophage infiltration as well as carbon loading in the peripheral lungs, and facilitated the resolution of emphysema and small airway remodeling in DEP-induced COPD rats. An in vitro free radical scavenging assay revealed robust antioxidant potential of GC in scavenging DPPH free radicals. Moreover, GC demonstrated potent capacities in reducing ROS production and enhancing SOD activity in BEAS-2B cells stimulated by DEPs. GC treatment significantly attenuated the increased level of IL-8 and MUC5AC from DEP-treated BEAS-2B cells. Mechanistically, GC treatment upregulated the protein level of Nrf-2 and could function via MAPK/NF-κB signaling pathways by suppressing the phosphorylation of p38, JNK and p65. Citrus peel extract is effective in decreasing oxidative stress and inflammatory responses of the peripheral lungs to DEP exposure. These protective effects further contributed to the resolution of COPD-like pathologies.


Evaluation of Prepectoral Implant Placement and Complete Coverage with TiLoop Bra Mesh for Breast Reconstruction: A Prospective Study on Long-Term and Patient-Reported BREAST-Q Outcomes.
Breast reconstruction is rapidly evolving, because of the changing face of cancer surgery and the growing acceptance of acellular dermal matrices and synthetic meshes. Although some early reports showed encouraging results after prepectoral breast reconstruction, there is a paucity of data on long-term outcomes. Between January of 2012 and March of 2015, 179 patients undergoing mastectomy were enrolled at the authors' institution. Patients underwent mastectomy and immediate prepectoral breast reconstruction with the definitive implant entirely wrapped in a titanium-coated polypropylene mesh (TiLoop). The BREAST-Q questionnaire was administered before surgery and after 2 years. Capsular contracture was evaluated using the Baker scale. Oncologic, surgical, and aesthetic outcomes and changes in BREAST-Q score were analyzed over time. Average follow-up was 38.5 months. A total of 250 mastectomies were performed. The locoregional recurrence rate was 2.1 percent. Complications requiring reoperation were recorded in six patients (2.4 percent) and implant removal was necessary in three cases (1.2 percent), followed by reconstruction with submuscular expanders. Grade IV capsular contracture was detected in five breasts (2 percent), whereas 212 breasts were evaluated as grade I (84.8 percent), 28 breasts as grade II (11.2 percent), and five breasts as grade III (2 percent). Patients reported significant high rates in the BREAST-Q overall Satisfaction with Outcome (73.8), overall Satisfaction with Breasts (72.5), Psychosocial Well-being (77.7), and Sexual Well-being (57.9), scoring a significant increase in these domains from the preoperative period to the postoperative period (p < 0.05). The authors report encouraging results of a prepectoral direct-to-implant reconstruction technique using a synthetic mesh, supporting the evaluation of the muscle-sparing subcutaneous approach as a valid alternative to traditional submuscular reconstruction. Therapeutic, IV.


Role of Clinical Insight at First Month in Predicting Relapse at the Year in First Episode of Psychosis (FEP) Patients.
Clinical insight constitutes a useful marker of the progress and outcome of the First Episode of Psychosis (FEP), and lack of insight has been associated with more severe psychopathology, treatment non-adherence, and rehospitalization/relapse. In this study, we aimed to further investigate the possible role of insight as a predictor of relapse, its relation to diagnosis, and other parameters of positive psychotic symptomatology (delusions, hallucinations, and suspiciousness). The Athens FEP study employed a prospective, longitudinal cohort design in which consecutive newly diagnosed patients with psychosis were interviewed and asked to voluntarily participate after completing informed consent. A total of 88/225 patients were examined at three different time points (baseline, month, and year). Their scores in the relevant items of the Positive and Negative Syndrome Scale (PANSS) were compared (G12 for insight, P1 for delusions, P3 for hallucinations, and P6 for suspiciousness), and they were further associated to diagnosis and the outcome at the end of the year (remission/relapse). In total, 22/88 patients with relapse at the year had greater scores in G12 for both the month and the year, and this finding was corroborated after adjusting the statistical analysis for demographics, diagnosis, social environment, and depression via multiple logistic regression analysis. Moreover, delusions and suspiciousness were significantly higher in patients diagnosed with non-affective psychosis compared to those diagnosed with affective psychosis (p < 0.001) at the first month. Lack of insight at the first month may serve as a predictor of relapse at the year.


Outcomes of Using IVC Filters in Patients with Malignancy at an Academic Medical Center.
Systemic anticoagulation is regarded as optimal treatment and prophylaxis of venous thromboembolism (VTE). In malignancy, bleeding risk is increased while the patients remain hypercoagulable, making anticoagulation management troublesome. Inferior vena cava (IVC) filters have emerged as an option in the management of VTE, especially when anticoagulant agents are contraindicated. There is limited data on the overall outcomes of patients with malignancy and IVC filter placement. This descriptive study identifies individuals with filters placed and reviews outcomes to guide appropriate care of patients with malignancy and VTE. We performed a retrospective chart review of 115 patients with malignancy who had a filter placed between July 2014 and December 2016. Eighty-seven patients were tracked until December 2017 for significant events (VTE and/or death). In total, 61% ( n = 70) had metastatic solid tumor malignancy and 77% ( n = 88) were receiving anticoagulation therapy prior to IVC filter placement. Fifty-three percent ( n = 61) had bleeding events and 25% ( n = 29) had thrombocytopenia. Patients with isolated solid tumors receiving frequent surgery were also common recipients of filters. Sixty-six percent (57/87) of patients had a significant event; 85% of them were anticoagulated. Eighty-two percent of events occurred within 6 months of filter placement, with death occurring on average within 5 months of placement. Overall, use of IVC filters was more common in cancer patients who developed bleeding complications on anticoagulation and with metastatic malignancy. However, in patients with metastatic or hematologic disease, filter placement did not prevent all-cause mortality. Individualized risk-benefit consideration is needed before IVC filters are placed.


Influence of angiotensin converting enzyme insertion/deletion polymorphism on long-term total graft occlusion after coronary artery bypass surgery.
The renin-angiotensin system has a very important role in coronary thrombosis and restenosis. Plasma angiotensin converting enzyme (ACE) activity is associated with an insertion/deletion polymorphism in the gene coding for ACE. It is known that there is a strong correlation between ACE DD and atherosclerosis. However, little has been documented about its role in venous graft failure. The objective of this study was to investigate the relationships among the ACE gen polymorphism and long-term vein graft occlusion. The study population consisted of 87 consecutive white patients with symptomatic coronary artery disease in the previous month, who had had aorto-coronary bypass surgery (ACBS) more than 5 years back and who underwent coronary angiography for diagnostic purposes. On the same day of angiography, 10 mL whole blood was taken for ACE gene insertion/deletion (I/D) polymorphism. Mean age of the patients was 64.4 +/- 8.6 years, and 71 (82%) of the patients were men. The average ACBS time was 7.9 +/- 1.9 years. The ACE genotype was II in 15 patients (17.2%), ID in 47 patients (54.0%), and DD in 25 patients (28.7%). Thus, D allele frequency was .82. There was no significant difference between the cases with regard to age, body mass index, blood pressure status, plasma glucose level, plasma lipid profile, smoking status, average of ACBS time or family history of coronary heart disease. In ACE II group 5 patients had total venous graft occlusion, in ACE ID group 27 patients had total occlusion and in ACE DD group 20 patients had at least one graft total occlusion. The frequency of the venous graft occlusion about total venous grafts is 36% in the ACE II group, 49% in the ACE ID group, and 80% in the ACE DD group (P = .01). The ACE I/D gene polymorphism is associated with long-term survival of venous conduit. The ACE DD genotype or D allele influences the angiographic outcome of patients post-ACBS. These data suggest that routine determination of the ACE genotype may help identify patients who are at higher risk of venous graft failure after ACBS.


alpha-Adrenoceptor subtypes in cardiovascular regulation.
A great deal of experimental observations at alpha-adrenoceptors may be explained if two points are considered: (1) the alpha 1-/adrenoceptor ratio (selectivity ratio) of a given drug and (2) the ratio of alpha 1-/adrenoceptors in the target organ or tissue. The alpha 1-/alpha 2-selectivity ratio for 10 agonists was determined in pithed rats by their hypertensive effect in the presence or absence of the antagonists rauwolscine or prazosin, respectively. Treatment with a beta-blocking agent made it possible to test drugs with additional beta-adrenergic potencies (phenylethylamines). Methoxamine exerted the highest alpha 1-/alpha 2-selectivity ratio, the azepine derivative B-HT 920 the lowest ratio, i.e., the highest selectivity for alpha 2-adrenoceptors. Using the two selective agonists methoxamine and B-HT 920, respectively, the alpha 1-/alpha 2-adrenoceptor ratio (importance) in several target systems was estimated (determination of equieffective doses). Results indicated the prevalence of alpha 1-adrenoceptors in the nictitating membrane, and the equal importance of both subtypes at peripheral postsynaptic vascular sites in rats, as well as in cats. At presynaptic sites (cardiac nerve, rats), alpha 2-adrenoceptors are prevalent. A comparison of equieffective doses of B-HT 920 and clonidine in cats indicated the alpha 2-nature of the central adrenoceptors which mediate hypotension.


Hematologic interactions of endotoxin, tumor necrosis factor alpha (TNF alpha), interleukin 1, and adrenal hormones and the hematologic effects of TNF alpha in Corynebacterium parvum-primed rats.
Endotoxin reduces the release among other cytokines of tumor necrosis factor (TNF) and interleukin 1 (IL-1) and causes peripheral lymphopenia and a dose-response-dependent initial neutropenia followed by a monophasic neutrophilia. TNF alone induces lymphopenia and an initial neutropenia followed by a biphasic neutrophilia. IL-1 alone induces lymphopenia and a monophasic neutrophilia. TNF-plus-IL-1 caused a greater lymphopenia than either monokine alone, suggesting that both monokines contribute to LPS-induced lymphopenia. TNF-plus-IL-1 induced neutropenia similar in magnitude to that induced by TNF alone and induced a neutrophilia significantly greater than that induced by either monokine alone, suggesting that LPS-induced neutropenia is caused by TNF, while LPS-induced neutrophilia is due to the combined effects of TNF and II-1. TNF and IL-1 were administered together with LPS to simulate the in vivo condition of endogenous monokine release during gram-negative bacteremia. TNF combined with LPS increased both the duration and magnitude of LPS-induced lymphopenia, LPS-induced neutropenia, and LPS-induced neutrophilia. TNF-plus-LPS treated rats at 2 hours after injection exhibited a striking 93% decrease in bone marrow neutrophils even though no peripheral neutrophilia was yet apparent, suggesting that the subsequent neutrophilia was due to demargination and recirculation of neutrophils sequestered in the peripheral vasculature immediately after their release from the bone marrow. Epinephrine, which causes neutrophilia by demargination but not by release of marrow neutrophils, reversed the initial neutropenia in TNF-plus-LPS-treated rats and increased the neutrophilia. IL-1 combined with LPS increased LPS-induced neutrophilia, suggesting that endogenous IL-1 also contributed to LPS-induced neutrophilia. Corynebacterium parvum-primed rats with hyperplasia of the monocyte-macrophage system and treated with TNF differed from naive rats treated with TNF in that the second peak was as great as the initial peak of neutrophilia, supporting the hypothesis that the second peak of TNF-induced neutrophilia is due to the release of endogenous monokines. In conclusion, exogenous TNF, IL-1, and adrenal hormones affect circulating numbers of lymphocytes and neutrophils in a fashion consistent with their postulated endogenous role in the regulation of leukocyte trafficking during bacterial infection.


Identification and characterization of peptides mimicking the epitopes of metalloprotease of Schistosoma japonicum.
In an attempt to isolate and characterize peptides mimicking epitopes of metalloprotease and explore their immunological protection against Schistosoma japonicum (S. japonicum), polyclonal anti-metalloprotease sera was prepared to screen a 12-mer random peptide library to isolate phages binding specially to antisera IgG. Then, phage ELISA, animal immunization, DNA sequencing, Western blotting and enzymatic activity neutralizing analysis were used to characterize the selected phage clones. All of ten randomly picked clones were shown to be positive. Five peptides of different amino acid sequences deduced from DNA sequences were obtained and two of them (peptides 2 and 3) could induce significant reduction (31.0% and 31.8%, respectively) in worm burden and high reduction (52.6% and 54.9%, respectively) in liver eggs per gram (LEPG), while, unexpectedly, others (peptides 1, 4 and 5) could not elicit enough protection against infection of S. japonicum. Peptides 2 and 3 could be recognized by S. japonicum infected mouse sera (IMS) and could elicit neutralizing Abs. The results show that peptides 2 and 3 are antigenic and immunogenic. They are true mimics of epitopes of metalloprotease and useful as novel vaccine candidates against S. japonicum.


Immunohistological demonstration of CaV3.2 T-type voltage-gated calcium channel expression in soma of dorsal root ganglion neurons and peripheral axons of rat and mouse.
Previous behavioral studies have revealed that CaV3.2 T-type calcium channels support peripheral nociceptive transmission and electrophysiological studies have established the presence of T-currents in putative nociceptive sensory neurons of dorsal root ganglion (DRG). To date, however, the localization pattern of this key nociceptive channel in the soma and peripheral axons of these cells has not been demonstrated due to lack of isoform-selective anti-CaV3.2 antibodies. In the present study a new polyclonal CaV3.2 antibody is used to localize CaV3.2 expression in rodent DRG neurons using different staining techniques including confocal and electron microscopy (EM). Confocal microscopy of both acutely dissociated cells and short-term cultures demonstrated strong immunofluorescence of anti-CaV3.2 antibody that was largely confined to smaller diameter DRG neurons where it co-localized with established immuno-markers of unmyelinated nociceptors, such as, CGRP, IB4 and peripherin. In contrast, a smaller proportion of these CaV3.2-labeled DRG cells also co-expressed neurofilament 200 (NF200), a marker of myelinated sensory neurons. In the rat sciatic nerve preparation, confocal microscopy demonstrated anti-CaV3.2 immunofluorescence which was co-localized with both peripherin and NF200. Further, EM revealed immuno-gold labeling of CaV3.2 preferentially in association with unmyelinated sensory fibers from mouse sciatic nerve. Finally, we demonstrated the expression of CaV3.2 channels in peripheral nerve endings of mouse hindpaw skin as shown by co-localization with Mrgpd-GFP-positive fibers. The CaV3.2 expression within the soma and peripheral axons of nociceptive sensory neurons further demonstrates the importance of this channel in peripheral pain transmission.


A microCT-based atlas of the central nervous system and midgut in sea spiders (Pycnogonida) sheds first light on evolutionary trends at the family level.
Pycnogonida (sea spiders) is the sister group of all other extant chelicerates (spiders, scorpions and relatives) and thus represents an important taxon to inform early chelicerate evolution. Notably, phylogenetic analyses have challenged traditional hypotheses on the relationships of the major pycnogonid lineages (families), indicating external morphological traits previously used to deduce inter-familial affinities to be highly homoplastic. This erodes some of the support for phylogenetic information content in external morphology and calls for the study of additional data classes to test and underpin in-group relationships advocated in molecular analyses. In this regard, pycnogonid internal anatomy remains largely unexplored and taxon coverage in the studies available is limited. Based on micro-computed X-ray tomography and 3D reconstruction, we created a comprehensive atlas of in-situ representations of the central nervous system and midgut layout in all pycnogonid families. Beyond that, immunolabeling for tubulin and synapsin was used to reveal selected details of ganglionic architecture. The ventral nerve cord consistently features an array of separate ganglia, but some lineages exhibit extended composite ganglia, due to neuromere fusion. Further, inter-ganglionic distances and ganglion positions relative to segment borders vary, with an anterior shift in several families. Intersegmental nerves target longitudinal muscles and are lacking if the latter are reduced. Across families, the midgut displays linear leg diverticula. In Pycnogonidae, however, complex multi-branching diverticula occur, which may be evolutionarily correlated with a reduction of the heart. Several gross neuroanatomical features are linked to external morphology, including intersegmental nerve reduction in concert with trunk segment fusion, or antero-posterior ganglion shifts in partial correlation to trunk elongation/compaction. Mapping on a recent phylogenomic phylogeny shows disjunct distributions of these traits. Other characters show no such dependency and help to underpin closer affinities in sub-branches of the pycnogonid tree, as exemplified by the tripartite subesophageal ganglion of Pycnogonidae and Rhynchothoracidae. Building on this gross anatomical atlas, future studies should now aim to leverage the full potential of neuroanatomy for phylogenetic interrogation by deciphering pycnogonid nervous system architecture in more detail, given that pioneering work on neuron subsets revealed complex character sets with unequivocal homologies across some families.


Presynaptic initiation by action potentials of retrograde signals in developing neurons.
Until recently, the only means by which electrical activity was believed to initiate retrograde signals was via postsynaptic events: modulated synthesis or release of trophic factors. We have evidence in chick embryos for a presynaptic initiation of retrograde signals from the retina to the isthmo-optic nucleus, which is known to undergo 55% neuron death between embryonic days 12 and 17 and to become laminated during this period. Intraocular injections of saxitoxin just before embryonic day 14 reduce neuron death and prevent lamination in the isthmo-optic nucleus within as few as 6 hr. We show that these rapid effects are attributable to the direct action of saxitoxin on the isthmo-optic terminals. Alternative possibilities, such as an indirect effect via the target cells, are ruled out by control experiments. Normally, action potentials may lead to a chain of second messenger events in the axon terminal that is signaled retrogradely via the transport of a long-lived second messenger.


Oral health in Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy (APECED).
APECED (Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy) is a rare autosomal recessive disease characterised primarily by sequential immune-mediated destruction of endocrine tissues, chronic oral or mucocutaneous candidiasis and ectodermal disorders, including hypoplasia of dental enamel. This was to investigate the oral health and presence of enamel defects in a cohort of patients with APECED. 16 patients with APECED (mean age of 13.9 years) were matched for age and gender with healthy controls. A comprehensive medical, dental and drug history was recorded, followed by a clinical assessment of oral health which was determined by assessing periodontal treatment needs, prevalence of dental caries, erosion, fluorosis and enamel defects. The estimated time of the development of the enamel defects and the contemporaneous medical diagnosis were recorded. Oral health of patients with APECED was poor compared with controls, with a higher prevalence of periodontal disease, caries and erosion. There was a significantly (P < 0.05) higher prevalence of enamel defects in the study group. The enamel defects were mostly hypoplastic in the form of pits, missing enamel and grooves. The enamel defects occurred in a chronological pattern. There was a strong association between the estimated time of defective enamel formation and a history of hypoparathyroidism. Gastrointestinal dysfunction and a history of chronic mucocutaneous candidiasis were also associated with the presence of enamel defects. The oral health of individuals with APECED was poor compared with controls with a higher prevalence of periodontal disease, caries, erosion and enamel defects. The enamel defects in the study population occurred in a chronological pattern and some were associated with a history of systemic disease during the period of tooth development.


Effects of lipopolysaccharide on P-glycoprotein expression and activity in the liver and kidneys.
There have been many reports that P-glycoprotein expression and activity are altered during sepsis, but few of them have examined such changes over 72 h. In this study, we examined the effect of lipopolysaccharide (LPS, 5mg/kg, ip) on P-glycoprotein expression (Western blotting) and activity (rhodamine-123 (Rho123) pharmacokinetics) in liver and kidneys for 7 days. On day 1 after LPS administration, hepatic P-glycoprotein expression and activity significantly decreased. On day 3, hepatic P-glycoprotein expression significantly increased compared with the control group, while activity had returned to the control level. On day 7, hepatic P-glycoprotein expression returned to the control level. There were no significant changes in P-glycoprotein expression or activity in the kidneys after LPS administration. The amount of Rho123 excretion in urine remained unchanged with (4.2%) or without (4.0%) LPS administration, but the amount of Rho123 excretion in bile decreased from 2.0 to 0.7% with LPS administration. Our findings suggested that hepatic P-glycoprotein expression and activity decreased on day 1 but recovered within 3 days, but there were no significant differences in the kidneys after LPS administration. These results suggested that the change in P-glycoprotein activity might be due to change in P-glycoprotein expression in the liver rather than the kidneys.


[Does Impulsivity Affect a Long-term and Working Memory in rats?].
In the present paper usingthe method of delay discounting three groups of animals were discovered: a) those that at choice between immediate weak and delayed strong rewards have chosen an immediate reinforcement (high impulsive rats); b) those that were able to inhibit its own behavior and get the delayed reinforcement (low impulsive rats); and c) the rats with both types of reactions. In the water maze the different groups of rats did find a hidden platform for different time, swum various distance and with different speed. The differences however were significant only at overall comparison (for all days and trials) of the above mentioned parameters of the water maze learning. ANOVAs Group x Days, Group x Trials, and Groups x Days x Trials interactions were insignificant. The data obtained indicate that the difference between groups was appeared evidently due to the difference in general motor activity, rather than difference in their cognitive abilities assessed by reference and working memory tasks.


An acute toxic neuropathy caused by organo-phosphate poisoning in hens.
Organophosphorus compounds can induce an acute toxic peripheral neuropathy. In hens, the acute peripheral neuropathy was induced by poisoning with organo-phosphorus compound (OPC)--tri-ortho-cresyl phosphate (TOCP). In the course of an acute TOCP-induced toxic neuropathy in hens the activity of following enzymes was analysed: asparaginase, glutaminase, glutamat-dehydrogenase, AMP and adenosine deaminases and 5'nucleotidase; ALT (SGPT), AST (SGOT) and proteins levels were estimated. A decrease in activity of all analysed enzymes was observed; the amount of proteins was increased. The biochemical changes display the slowing or stoppage in axonal transport of proteins. The disturbance of axoplasmic flow and the axonal demyelination may be considered as an attribute of peripheral neuropathy. (Tab. 1, Fig. 1, Ref. 32.).


Microbial Biotransformation of a Polyphenol-Rich Potato Extract Affects Antioxidant Capacity in a Simulated Gastrointestinal Model.
A multistage human gastrointestinal model was used to digest a polyphenol-rich potato extract containing chlorogenic acid, caffeic acid, ferulic acid, and rutin as the primary polyphenols, to assess for their microbial biotransformation and to measure changes in antioxidant capacity in up to 24 h of digestion. The biotransformation of polyphenols was assessed by liquid chromatography-mass spectrometry. Antioxidant capacity was measured by the ferric reducing antioxidant power (FRAP) assay. Among the colonic reactors, parent (poly)phenols were detected in the ascending (AC), but not the transverse (TC) or descending (DC) colons. The most abundant microbial phenolic metabolites in all colonic reactors included derivatives of propionic acid, acetic acid, and benzoic acid. As compared to the baseline, an earlier increase in antioxidant capacity (T = 8 h) was seen in the stomach and small intestine vessels as compared to the AC (T = 16 h) and TC and DC (T = 24 h). The increase in antioxidant capacity observed in the DC and TC can be linked to the accumulation of microbial smaller-molecular-weight phenolic catabolites, as the parent polyphenolics had completely degraded in those vessels. The colonic microbial digestion of potato-based polyphenols could lead to improved colonic health, as this generates phenolic metabolites with significant antioxidant potential.


Novel PFA-Based Inorganic Three-Phase Foam for Inhibiting Coal Spontaneous Combustion.
Fire accidents caused by coal spontaneous combustion usually lead to a large loss of coal resources and casualties. Not only that, the greenhouse effect is polluted while the environment is polluted. At present, the commonly used fire-extinguishing materials such as water, inhibitors, and organic foams have the disadvantages of poor stability and short fire-extinguishing cycles. It is difficult to effectively suppress coal spontaneous combustion and quickly extinguish the fire for a long time. To suppress the spontaneous combustion of coal, the research team proposed an inorganic three-phase foam with a high foam expansion rate, good cohesiveness, and excellent stability. In the formulation, pulverized fly ash (PFA) is used as the matrix, sodium dodecyl benzene sulfonate (SDBS) and α-olefin sulfonate (AOS) are used as foaming agents, curdlan is used as the foam stabilizer, and sodium silicate is the binder. The compound foaming agent with the best performance is optimized, through the two-group compounding test. The composite foaming agent's optimal compound ratio is SDBS/AOS (3:2). The optimal ratio of inorganic three-phase foam (ITPF) components was obtained through the control variable method experiment. The water-cement ratio is 5:1, the composite foaming agent is 0.2%, the curdlan is 0.5%, and the sodium silicate is 1.6%. In addition, it has been determined by experiments that ITPF has the strongest foaming ability when the pH value is 9 and the temperature is 60 °C. The fire-extinguishing performance of the new material ITPF was investigated by thermogravimetry and coal spontaneous combustion tendency test. It has been observed that the new material has the effect of cooling down and isolating coal from contact with oxygen. The results show that the new material ITPF has the potential to prevent coal spontaneous combustion.


Interference and interferometry in electron holography.
This paper reviews the basics of electron holography as an introduction of the holography part of this special issue in Microscopy. We discuss the general principle of holography and interferometry regarding measurements and analyses of phase distributions, first using the optical holography. Next, we discuss physical phenomena peculiar to electron waves that cannot be realized by light waves and principles of electromagnetic field detection and observation methods. Furthermore, we discuss the interference optical systems of the electron waves and their features, and methods of reconstruction of the phase information from electron holograms, which are essential for realization of practical electron holography. We note that following this review application of electron holography will be discussed in detail in the papers of this special issue.


Pediatric patients with common variable immunodeficiency: long-term follow-up.
Common variable immunodeficiency (CVID) is the most common form of symptomatic primary immunodeficiency disease. It is characterized by hypogammaglobulinemia, increased predisposition to infections, autoimmunity, and cancer. This study was performed to evaluate the clinical and immunological features of a group of pediatric patients with CVID. The study population comprised 69 individuals with CVID diagnosed during childhood. The patients were followed up for a mean (SD) period of 5.2 (4.3) years. The mean diagnostic delay was 4.4 (3.6) years, which was significantly lower in patients who were diagnosed recently. Children were classified according to 5 clinical phenotypes: infections only (n=39), polyclonal lymphocytic infiltration (n=17), autoimmunity (n=12), malignancy (n=7), and enteropathy (n=3). Postdiagnosis survival (10-year) was 71%. The high percentages of pediatric patients with CVID in Iran may be due to the considerable prevalence of parental consanguinity in the region and an underlying genetic background.


Rapid detox: understanding new treatment approaches for the addicted patient.
Despite substantive advances in understanding of genetic and biochemical basis of substance abuse and addiction in the last decade, little information has been translated into alternative treatment models for the addicted patient. Rapid detox, an alternative form of detox treatment, is gaining in both acceptance and popularity. To increase readers' understanding of the neurobiology of addiction and the mode of action of new detox approaches for patients addicted to opiate drugs. A review of the current literature pertaining to rapid detox. Rapid detox is a viable alternative for selected patients attempting to detox from opiate agents of abuse. Increasing knowledge of new treatment approaches allows nurses working to assist addicted patients in planning and receiving treatment based on new awareness of the neurobiology of addiction.


Neutron, fluorescence, and optical imaging: An in situ combination of complementary techniques.
An apparatus which enables the simultaneous combination of three complementary imaging techniques, optical imaging, fluorescence imaging, and neutron radiography, is presented. While each individual technique can provide information on certain aspects of the sample and their time evolution, a combination of the three techniques in one setup provides a more complete and consistent data set. The setup can be used in transmission and reflection modes and thus with optically transparent as well as opaque samples. Its capabilities are illustrated with two examples. A polymer hydrogel represents a transparent sample and the diffusion of fluorescent particles into and through this polymer matrix is followed. In reflection mode, the absorption of solvent by a nile red-functionalized mesoporous silica powder and the corresponding change in fluorescent signal are studied.