The Incidence of Invasive Fungal Infections in Patients With AML Treated With a Hypomethylating Agent.
Newly diagnosed patients with acute myeloid leukemia (AML) who receive induction with a hypomethylating agent (HMA) are often neutropenic with an increased risk for invasive fungal infections (IFIs). This study analyzed the incidence and risk factors for IFIs in these patients, evaluated clinical patterns in antifungal prophylaxis, and assessed the diagnostic utility of tests in this setting. We studied 117 newly diagnosed patients with AML treated with HMAs at our center, divided into groups based on concern for IFI (cIFI: all possible, probable, and proven IFIs) versus no concern for IFI. The Fisher exact test compared patients with cIFI versus without, and a multivariable logistic regression model estimated odds for cIFI. Sixty-seven (57%) patients had cIFI, with 48 possible IFIs, 17 probable, and 2 proven cases. There was no difference in incidence based on home zip code, but the presence of chronic obstructive pulmonary disease was highly associated with cIFI (P = .001), as was male gender (P = .01). Neutropenia at treatment initiation was borderline in significance (P = .08). In diagnostics, 9% of patients had positive serum fungal markers, and 30 patients underwent bronchoscopy, with only 27% of cases yielding positive results. There was a difference in treatment regimens between patients receiving antifungal prophylaxis with mold coverage versus without mold coverage with respect to cIFI (P = .04). cIFI in patients with AML treated with HMAs remains significant, especially in males and those with chronic obstructive pulmonary disease, who were found to be at higher risk. This may prompt clinicians to consider anti-mold prophylaxis in this setting.


Purification of Native Mfa1 Fimbriae from Porphyromonas gingivalis.
Fimbriae of the periodontal pathogen Porphyromonas gingivalis mediate its colonization through associations with other bacteria and host tissues. P. gingivalis generally expresses two distinct fimbrial types, FimA and Mfa1. In P. gingivalis ATCC 33277, FimA fimbriae are present as long filaments easily detached from cells, whereas Mfa1 fimbriae are short filaments compactly bound to the cell surface. Because of this unique characteristic, FimA fimbriae have been selectively and easily isolated from the bacterial cell surface through mechanical shearing such as by pipetting and stirring. However, P. gingivalis ATCC 33277 harbors a mutation in the gene encode the fimbrial length regulator, FimB, and thus produces unusually long FimA fimbriae length. Hence, mechanical shearing to remove FimA is potentially applicable only for this type strain. Here we present protocols to purify intact Mfa1 fimbriae from a fimA-deficient mutant strain. Mfa1 fimbriae are purified from cell lysates, using a French pressure cell and through ion-exchange chromatography. The purity of Mfa1 fimbriae can be confirmed through sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunoblotting, and electron microscopy.


A comparison of two pre-race medical screening tools in 5771 running race entrants-SAFER XXVIII.
To determine if two pre-race screening tools (abbreviated tool of two open-ended pre-race medical screening questions [ABBR] vs. a full pre-race medical screening tool [FULL]) identify running race entrants at higher risk for medical encounters (MEs) on race day. 5771 consenting race entrants completed both an ABBR and a FULL pre-race screening questionnaire for the 2018 Comrades Marathon (90 km). ABBR tool questions were (1) allergies, and (2) known medical conditions and/or prescription medication use. The FULL tool included multiple domains of questions for chronic diseases including cardiovascular disease (CVD), symptoms, risk factors, allergies and medication use. ABBR responses were manually coded and compared to the FULL tool. The prevalence (%: 95%CI), and the test for equality of prevalence of entrants identified by the ABBR vs. FULL tool is reported. The ABBR identified fewer entrants with allergies (ABBR = 7.9%; FULL = 10.4%: p = 0.0001) and medical conditions/medication use (ABBR = 8.9%; FULL = 27.4%: p = 0.0001). The ABBR tool significantly under-reported entrants with history of cardiovascular disease (CVD), CVD risk factors, other chronic diseases and prescription medication vs. the FULL tool (p = 0.0001). The ABBR tool identified fewer entrants in the "high" (ABBR = 3.4%; FULL = 12.4%) and "very high" risk (ABBR = 0.5%; FULL = 3.4%) categories for race day MEs (p = 0.0001). An abbreviated pre-race screening tool significantly under-estimates chronic medical conditions, allergies, and race entrants at higher risk for MEs on race day, compared with a full comprehensive screening tool. We recommend that a full pre-race medical screening tool be used to identify race entrants at risk for MEs.


Treatment of proximal humeral fractures with Polarus nail fixation.
A chart review of 20 patients who sustained acute proximal humeral fractures and who were treated by surgical stabilization with locked antegrade humeral intramedullary nails (Polarus nails) was undertaken. The clinical outcome measurements were fracture healing, infection, and neurologic injury. Radiologic outcome measurements included fracture alignment, loosening, fixation and hardware failure, and malunion and nonunion. Of 20 fractures, 11 healed without complications. The mean immediate postoperative and final radiographic valgus neck/shaft angulation measured 131 degrees. Of the 20 implants, 3 had proximal fixation screw loosening. Of the 20 implants, 2 underwent revision surgery for proximal fixation failure. With certain fracture types, the Polarus intramedullary humeral nail can be an effective implant. In fracture cases involving an unstable or comminuted lateral metaphyseal fracture, if the starting point extends into the greater tuberosity, fixation failure or fracture displacement may result.


Seasonal variations of insulin and some metabolites in dogfish plasma, Scyliorhinus canicula, L.
Plasma levels in insulin, glucose, ketone bodies, and lactate were analyzed during a 1-year period in the lesser spotted dogfish (Scyliorhinus canicula) in captivity. Plasma insulin levels fluctuated similarly for both sexes. The highest insulin levels were found during late prespawning (from January to March) and another increase was observed during the active feeding period (September and October). During the spawning period, insulin decreased and in the postspawning period the lowest values were reached. Glucose, however, showed a different trend. It was at a minimum in late prespawning and it reached its highest values in postspawning. It decreased again in September and October. Plasma ketone body levels were highest in late prespawning and could be considered as an alternative energy source for this hypoglycemic period. In the summer months plasma lactate levels rose, with maximum levels occurring in July.


Enhanced release of ammonia and hypoxanthine from exercising muscles in patients with idiopathic hypoparathyroidism.
Semiischemic forearm exercise tests were carried out in two patients with idiopathic hypoparathyroidism who had muscle cramps and high serum levels of creatine kinase. Although cubital venous lactate levels increased normally after forearm exercise, venous ammonia and hypoxanthine were greatly increased. The abnormal responses of ammonia and hypoxanthine were normalized 3 months after treatment with 1 alpha-hydroxyvitamin D3. These findings suggest that excess purine degradation occurred in exercising muscles of patients with idiopathic hypoparathyroidism.


Neurofunctional assessment of schizophrenia: a preliminary investigation of the presence of eye-tracking (SPEMs) and quality extinction test (QET) abnormalities in a sample of schizophrenic patients.
This preliminary study evaluated the simultaneous presence of abnormalities in the regulation of eye-tracking and neuropsychological tests performance (tactile extinction) in a sample of schizophrenic patients. Both those measures of central malfunctioning appears to be quite specific to schizophrenic disorders and more related to the trait, rather than state characteristics. Even though preliminary, the results indicate a significant relationship between abnormalities in SPEM regulation and the distribution of tactile abnormalities, with more left-side extinguishing patients showing abnormal SPEMs. Some interpretations of the findings are given in the context of current hypotheses on the neurofunctional abnormalities of schizophrenics.


Unilateral CHARGE association.
A case with a predominantly unilateral CHARGE association is reported. The CHARGE association refers to a combination of congenital malformations. This boy had left-sided anomalies consisting of choanal atresia, coloboma and peripheral facial palsy. The infant had a frontal encephalocele, an anomaly not included in the definitions of CHARGE association. even when anomalies are predominantly unilateral, the CHARGE association should be considered in the differential diagnosis.


Heavy and light chain contributions to antigen binding in an anti-digoxin chain recombinant antibody produced by transfection of cloned anti-digoxin antibody genes.
We used immunoglobulin gene transfection to study the effect that substituting an homologous light (L) chain for a parental L chain has on antigen fine specificity and affinity. High-affinity monoclonal anti-digoxin antibodies 26-10 and 40-100 were selected for study because their L chains are 92% homologous (although the H chains differ), and their binding with digoxin and digoxin analogs show very different properties. In order to generate a recombinant transfectoma, the genes encoding the 26-10 H and L chains were cloned. After the sequenced clones had been shown to contain the V gene and the transcriptional control elements, the H and L chain V region genes were subcloned into different expression vectors. Both constructs were transfected into myeloma J558L, a lambda 1 chain producer, to verify that the genetic constructs expressed correctly. The recombined 26-10 antibody was identical to parental 26-10 antibody in fine specificity and affinity. The 26-10 L chain construct was then transfected into a cell line, CR-101, that expresses the 40-100 H chain and a lambda 1 chain. The transfectoma 1E6, secreting 40-100 H chain and 26-10 L chain, was selected. Appropriate gene expression in 1E6 was proven by polymerase chain reaction cloning and sequencing. The fine specificity properties of the 1E6 recombinant derive from both the 40-100 and 26-10 antibodies; however, the affinity of 1E6 is 130 times less than that of the parental antibodies. We conclude that, in 1E6, the H and L chains are codominant in their influence on antigen specificity and that homologous pairing of H and L chains is required for optimal affinity.


[Basic technical aspects of removal of colonic polyps with the use of fibrocolonoscopes].
The authors describe the technical aspects, which observation makes it possible to safely remove polyps from any portion of the colon. Complications necessitating operative interventions were 3: one hemorrhage and two perforations of the colon.


Assessment of shallow groundwater contamination on Pari Island, Indonesia.
Freshwater on small islands is generally limited and relies on rainwater and groundwater. This study aimed to assess changes in shallow groundwater quality on Pari Island, Indonesia. Pari Island is a small island with an area of 41.32 ha and belongs to a monsoon climate. Also, being a residential island, it attracts many tourists. The approach was to assess the shallow groundwater quality of ten wells during the dry and wet seasons. Changes in water quality were evaluated using traditional hydrochemical analysis methods (Schoeller, Piper, and Gibbs diagrams) and ion ratios. Shallow groundwater quality in the study area showed different responses depending on the season. Therefore, each well responded differently to changes represented by changes in water quality. The change is controlled by various factors: evaporation (or water balance), geology, aquifer characteristics, tides, wind direction, and wave height. These factors trigger the fluctuation of groundwater and seawater interface, affecting the amount of rainwater and seawater transported to the freshwater aquifer layer. This water volume transported affects the process of rock weathering, dissolution, and dilution of contaminants in shallow groundwater.


Matrix diversion methods for improved analysis of perchlorate by suppressed ion chromatography and conductivity detection.
Two inline matrix diversion methods were developed for the sensitive analysis of perchlorate in a matrix comprising up to 1000 mg l(-1) of chloride, sulfate and bicarbonate ions using suppressed ion chromatography and conductivity detection. The first method used a cryptand C1 concentrator column, which exhibited a high selectivity for perchlorate ion over the other matrix anions. After retaining the sample anions in a concentrator column derivatized with a crytpand phase, a rinse step was implemented with a weak base to divert the matrix ions to waste while selectively retaining perchlorate in the concentrator column for subsequent analysis. The analysis was done using a 2mm IonPac AS16 or 2 mm IonPac AS20 separator column. The second method was a two-dimensional matrix diversion method with a focus on improving the detection sensitivity. The first dimension was used to achieve some resolution of the matrix ions from perchlorate. The perchlorate ion was then diverted into a concentrator column for subsequent analysis in the second dimension. By pursuing analysis using a 4mm IonPac AS16 or IonPac AS20 column in the first dimension and subsequently pursuing analysis using a 2mm IonPac AS16 or IonPac AS20 column format, excellent sensitivities were achieved when the first and second dimensions were operated at the same linear flow velocity (cm min(-1)). While sensitive detection of perchlorate in the low microg l(-1) regime was achieved by the above methods in the presence of matrix ions, superior recovery for perchlorate was demonstrated under a variety of matrix concentrations by the second method.


Smartphone-based dual radiometric fluorescence and white-light imager for quantification of protoporphyrin IX in skin.
The quantification of protoporphyrin IX (PpIX) in skin can be used to study photodynamic therapy (PDT) treatments, understand porphyrin mechanisms, and enhance preoperative mapping of non-melanoma skin cancers. We aim to develop a smartphone-based imager for performing simultaneous radiometric fluorescence (FL) and white light (WL) imaging to study the baseline levels, accumulation, and photobleaching of PpIX in skin. A smartphone-based dual FL and WL imager (sDUO) is introduced alongside new radiometric calibration methods for providing SI-units of measurements in both pre-clinical and clinical settings. These radiometric measurements and corresponding PpIX concentration estimations are applied to clinical measurements to understand mechanistic differences between PDT treatments, accumulation differences between normal tissue and actinic keratosis lesions, and the correlation of photosensitizer concentrations to treatment outcomes. The sDUO alongside the developed methods provided radiometric FL measurements (nW/cm2) with a demonstrated sub nanomolar PpIX sensitivity in 1% intralipid phantoms. Patients undergoing PDT treatment of actinic keratosis (AK) lesions were imaged, capturing the increase and subsequent decrease in FL associated with the incubation and irradiation timepoints of lamp-based PDT. Furthermore, the clinical measurements showed mechanistic differences in new daylight-based treatment modalities alongside the selective accumulation of PpIX within AK lesions. The use of the radiometric calibration enabled the reporting of detected PpIX FL in units of nW/cm2 with the use of liquid phantom measurements allowing for the estimation of in-vivo molar concentrations of skin PpIX. The phantom, pre-clinical, and clinical measurements demonstrated the capability of the sDUO to provide quantitative measurements of PpIX FL. The results demonstrate the use of the sDUO for the quantification of PpIX accumulation and photobleaching in a clinical setting, with implications for improving the diagnosis and treatment of various skin conditions.


[The diversity of leptin].
The role of leptin in regulation of energy homeostasis is well established, yet both the diagnostic as well as the therapeutic relevance of leptin in diet-induced obesity remains unresolved. Nevertheless, in the last few years, the substantial impact of leptin substitution in selected forms of monogenic obesity has advanced our knowledge about the neuroendocrine network of body weight regulation. Moreover, leptin seems to play a crucial role in intestinal nutrient reabsorption, regulation of blood pressure, fertility, inflammation and autoimmune diseases. A better understanding of these processes could possibly provide novel diagnostic and therapeutic options in the future.


Cathepsin E induces itch-related response through the production of endothelin-1 in mice.
This study investigated the pruritogenic potency of cathepsin E, an aspartic protease, and its mechanisms in mice. An intradermal injection of cathepsin E to the rostral back elicited scratching, an itch-associated response, of the injection site. This action was inhibited by the aspartic protease inhibitor pepstatin A, the endothelin ET(A) receptor antagonist BQ-123, and the opioid receptor antagonists naltrexone and naloxone, but not by the H(1) histamine receptor antagonist terfenadine, the proteinase-activated receptor-2 antagonist FSLLRY-NH(2), or mast cell deficiency. Pepstatin A inhibited scratching induced by intradermal injection of the mast-cell degranulator compound 48/80, but not by tryptase, a mast-cell mediator. An intradermal injection of cathepsin E increased endothelin-1 levels in the skin at the injection site. Preproendothelin-1 mRNA was present in primary cultures of keratinocytes, and immunohistochemistry using an antibody recognizing endothelin-1 and big-endothelin-1 revealed immunoreactivity in the epidermis, especially in the prickle and granular cell layers, but not in the basal cell layer. These results suggest that cathepsin E is an endogenous itch inducer, and that its action is mediated at least in part by the production of endothelin-1 in the epidermis.


Effect of etanercept on insulin secretion and insulin sensitivity in a randomized trial with psoriatic patients at risk for developing type 2 diabetes mellitus.
Tumor necrosis factor-alpha (TNF-alpha) inhibitors have been used in the treatment of psoriasis, which is associated with the insulin resistance syndrome. The purpose of this study was to determine the effect of etanercept, a TNF-alpha inhibitor, on insulin secretion and insulin sensitivity in psoriatic patients with high risk factors to develop type 2 diabetes mellitus. Randomized double blind clinical trial with 2 weeks of follow-up. The allocation was done by simple randomization. The investigation was performed in 12 psoriatic patients with indication of systemic treatment and 2 or more risk factors for type 2 diabetes mellitus. Patients with infections, topical corticosteroids or salicylic acid ointments for 6 weeks before the study, diabetes, acromegaly, cancer and other systemic diseases were excluded. All subjects gave written informed consent to participate in the study and the protocol was approved by the hospital-based Ethical Committee. Etanercept was injected in a subcutaneous dose of 25 mg in 1 ml twice by week for 2 weeks or 1 ml of saline solution as placebo. Insulin secretion was estimated with the formula for the homeostasis model analysis beta-cell function index and insulin sensitivity was assessed using the euglycemic-hyperinsulinemic clamp technique. There was no significant difference in insulin secretion and insulin sensitivity with etanercept. Fasting serum insulin levels were decreased in the etanercept group (146 +/- 117-111 +/- 87 pmol/l, P = 0.04). Etanercept did not modify insulin secretion and insulin sensitivity in psoriatic patients with risk factors for type 2 diabetes mellitus.


Characterization of primary human hepatocytes, HepG2 cells, and HepaRG cells at the mRNA level and CYP activity in response to inducers and their predictivity for the detection of human hepatotoxins.
In the pharmaceutical industry, improving the early detection of drug-induced hepatotoxicity is essential as it is one of the most important reasons for attrition of candidate drugs during the later stages of drug development. The first objective of this study was to better characterize different cellular models (i.e., HepG2, HepaRG cells, and fresh primary human hepatocytes) at the gene expression level and analyze their metabolic cytochrome P450 capabilities. The cellular models were exposed to three different CYP450 inducers; beta-naphthoflavone (BNF), phenobarbital (PB), and rifampicin (RIF). HepG2 cells responded very weakly to the different inducers at the gene expression level, and this translated generally into low CYP450 activities in the induced cells compared with the control cells. On the contrary, HepaRG cells and the three human donors were inducible after exposure to BNF, PB, and RIF according to gene expression responses and CYP450 activities. Consequently, HepaRG cells could be used in screening as a substitute and/or in complement to primary hepatocytes for CYP induction studies. The second objective was to investigate the predictivity of the different cellular models to detect hepatotoxins (16 hepatotoxic and 5 nonhepatotoxic compounds). Specificity was 100% with the different cellular models tested. Cryopreserved human hepatocytes gave the highest sensitivity, ranging from 31% to 44% (depending on the donor), followed by lower sensitivity (13%) for HepaRG and HepG2 cells (6.3%). Overall, none of the models under study gave desirable sensitivities (80-100%). Consequently, a high metabolic capacity and CYP inducibility in cell lines does not necessarily correlate with a high sensitivity for the detection of hepatotoxic drugs. Further investigations are necessary to compare different cellular models and determine those that are best suited for the detection of hepatotoxic compounds.


Synthesis and evaluation of nitrostyrene derivative compounds, new snake venom phospholipase A2 inhibitors.
Several nitrostyrene derivatives were synthesized and their inhibitive activities on phospholipase A(2) (PLA(2)) from Bothrops jararacussu venom were evaluated. Some compounds were very efficient as inhibition agents against edema-inducing, enzymatic and myotoxic activities. Data revealed that the size of the substitute and substitution position in the nitrostyrene moiety had important influence on the inhibition capacities. The enzymatic kinetic studies show that the nitrostyrene derivatives compounds inhibit PLA(2) in a non-competitive manner. The electronic, molecular and topologic parameters were calculated using ab initio quantum calculations (density functional theory-DFT) and analyzed by chemometric methods (principal component analysis (PCA) and hierarchical cluster analysis (HCA)) in order to build models able to establish relationships between the electronic features and the structure-activity presented by the target compound. Compounds with the nitro group in the ortho, meta and para position (compounds 2-4) on the aromatic ring were more efficient in the inhibition of PLA(2) activity in all tests. These results indicate that the influence of the nitro group in the aromatic ring is, in fact, important. In addition, quantum chemistry calculations show that compounds with a higher capacity of inhibiting PLA(2) present lower values of highest occupied molecular orbital (HOMO) energy and polarizability, suggesting the formation of a charge-transferring complex between the nitrostyrene compounds and PLA(2).


Modified ablation index: a novel determinant of a successful first-pass left atrial posterior wall isolation.
Although a left atrial posterior wall isolation (LAPWI) in addition to a pulmonary vein isolation is a well-accepted option for persistent atrial fibrillation (AF), a complete isolation can be challenging. This study aimed to evaluate the performance of a modified ablation index (AI) (AI/bipolar voltage along the ablation line) for predicting a durable LAPWI. The study included 55 consecutive patients, aged 65 ± 11 years, who underwent an electroanatomic mapping-guided LAPWI of AF. The association between the gaps (first-pass LAPWI failure and/or acute LAPW reconnections), voltage amplitude along the roof and floor lines, and thickness of the LAPW was investigated. Gaps occurred in 22 patients (40%) and in 26 (8%) of the 330 line segments. Gaps were associated with a relatively high bipolar voltage (3.38 ± 1.83 vs. 1.70 ± 1.12 mV, P < 0.0001) and thick LA wall (2.52 ± 1.15 vs. 1.42 ± 0.44 mm, P < 0.0001). A modified AI ≤ 199 AU/mV, bipolar voltage ≥ 2.64 mV, wall thickness ≥ 2.04 mm, and roof ablation line ≥ 43.4 mm well predicted gaps (AUCs: 0.783, 0.787, 0.858, and 0.752, respectively). A high-voltage zone, thick LAPW, and long roof ablation line appeared to be determinants of gaps, and a modified AI ≥ 199 AU/mV along the ablation lines appeared to predict an acute durable LAPWI.


The optimality concept and its clinical value.
To verify the clinical usefulness of the optimality concept in general and its prognostic value for later outcome, all babies born at all 14 maternity hospitals in Slovenia in the period from 1987 to 1991 (124,759 newborns) have been screened. In order to get an estimate of their condition Prechtl's original list of optimality has been adapted to 51 items representing mostly obstetric variables. The median of perinatal optimality scores for all newborns was 45 (six negative points) in mature, and 41 (10 negative points) in premature infants. Girls born at term scored better than mature boys, whereas there was no sex difference in the median score in prematures. Analysis of the data has shown that the majority of items which were non-optimal and which were associated with the greatest number of other non-optimal factors had to do with disturbances in oxygen supply. Children who developed cerebral palsy had a lower optimality score at birth than the remainder of the newborns. In these children the difference between the sexes is even more pronounced, to the advantage of the girls. Prematurely born children with spastic diplegia had a lower optimality score than mature children with diplegia. The opposite was noticed in children born prematurely and at term who developed spastic tetraparesis or dyskinesia. The present follow-up study has shown that predictions of disability were most accurate in the group of newborns who were clinically at risk at birth and who also had a low optimality score. The combination of both appraisals is the best way to identify newborns who need special attention.


Uterine metastasis from invasive ductal breast carcinoma: A case report with literature review.
Breast cancer is the leading cause of cancer death in women, and most breast cancer related deaths are due to metastases. Uterine metastases from breast cancer are uncommon and rarely reported in the literature. We described the case of a 50 years-old-woman who developed a uterine metastasis, 6 years after the diagnosis of an invasive ductal breast carcinoma. Indeed, although the patient was asymptomatic, the monitoring imaging examinations, particularly the computed tomography (CT) and the positron emission tomography/computed tomography (PET/CT), showed a myometrial lesion. Non-conservative total hysterectomy was performed. The anatomo-pathological examination revealed a myometrial metastasis from an invasive ductal breast carcinoma. Seventeen months after surgery, the patient had no pelvic recurrence, but lungs and bones metastases progressed despite chemotherapy. In the lack of guidelines of uterine metastases from breast cancer's management, we reviewed the existing literature with the aim to provide a rational framework for clinical presentation, diagnostic approach, histological findings and treatment of this rare and heterogeneous pathology. Uterine metastases of breast cancer are frequently revealed with metrorrhagia. They occur preferentially in tumours with initial lobular carcinoma, initial lymph node involvement and positive hormonal receptors.


Effects of acepromazine and dexmedetomidine, followed by propofol induction and maintenance with isoflurane anaesthesia, on the microcirculation of Beagle dogs evaluated by sidestream dark field imaging: an experimental trial.
To investigate the effects of intramuscularly administered acepromazine or dexmedetomidine on buccal mucosa microcirculation in Beagle dogs. Experimental, blinded, crossover study. A group of seven Beagle dogs aged 7.5 ± 1.4 years (mean ± standard deviation). Microcirculation was assessed on buccal mucosa using sidestream dark field videomicroscopy. After baseline measurements, 5 μg kg-1 dexmedetomidine or 30 μg kg-1 acepromazine were administered intramuscularly. After 10, 20 and 30 minutes, measurements were repeated. At 40 minutes after premedication, anaesthesia was induced with propofol intravenously and maintained with isoflurane. Measurements were repeated 50, 60 and 65 minutes after the injection of the investigated drugs. Analysed microcirculatory variables were: Perfused de Backer density, Perfused de Backer density of vessels < 20 μm, Proportion of perfused vessels and Proportion of perfused vessels < 20 μm. Heart rate (HR), systolic, diastolic (DAP) and mean (MAP) arterial pressures were recorded at the same time points. Macro- and microcirculatory variables were analysed using a linear mixed model with baseline as a covariate, treatment, trial period and repetition as fixed effects and time and dog as random effect. Results are presented as effect size and confidence interval; p values < 0.05 were considered significant. After acepromazine, Perfused de Backer density was greater during sedation and anaesthesia [3.71 (1.93-5.48 mm mm-2, p < 0.0001) and 2.3 (0.86-3.75 mm mm-2, p < 0.003)], respectively, than after dexmedetomidine. HR was significantly lower, whereas MAP and DAP were significantly higher with dexmedetomidine during sedation and anaesthesia (p < 0.0001 for all) compared with acepromazine. The sedative drugs tested exerted a significant effect on buccal mucosal microcirculation with a higher Perfused de Backer density after the administration of acepromazine compared with dexmedetomidine. This should be considered when microcirculation is evaluated using these drugs.


Deterministic global optimization of molecular structures using interval analysis.
The search for the global minimum of a molecular potential energy surface is a challenging problem. The molecular structure corresponding to the global minimum is of particular importance because it usually dictates both the physical and chemical properties of the molecule. The existence of an extremely large number of local minima, the number of which may increase exponentially with the size of the molecule, makes this global minimization problem extremely difficult. A new strategy is described here for solving such global minimization problems deterministically. The methodology is based on interval analysis, and provides a mathematical and computational guarantee that the molecular structure with the global minimum potential energy will be found. The technique is demonstrated using two sets of example problems. The first set involves a relatively simple potential model, and problems with up to 40 atoms. The second set involves a more realistic potential energy function, representative of those in current use, and problems with up to 11 atoms.


The consequences of orthodontic extrusion on previously intruded permanent incisors-A retrospective study.
The aim of this study is to compare the adverse effects that occur after orthodontic extrusion of teeth that have been traumatically intruded with those of similar teeth that have not experienced any trauma. The outcome of incisors intrusion can be affected by the patient's age, extent of injury, root development, and malocclusion. Orthodontic extrusion is a potential solution, but it may also cause complications. A retrospective study of the effects of extrusion of traumatically intruded teeth was carried out. The study group included 21 teeth in 14 patients. The control group included 32 teeth in 10 patients that underwent orthodontic extrusion with no history of trauma. Patients' age, gender, and stage of root development were recorded. The severity of the intrusion was classified as mild (<3 mm), moderate (3-6 mm), and severe (≥7 mm). A comparison of signs of pulp necrosis and root resorptions between the groups was made. The central incisor is the tooth that is most injured in 80.9% of cases. A majority of these incidents involve severe intrusion, which was found in 42.9% of cases. 90% of the traumatized teeth had already lost their vitality prior to orthodontic treatment. Various forms of root resorption were observed in the study group. In the control group, 31.2% of teeth showed signs of external root resorption, but no endodontic intervention was carried out during the follow-up period, as these teeth remained vital. Following intrusion, there is a high risk for root resorption and pulp necrosis. Orthodontic repositioning should be carried out with caution and mild force to prevent complications. Long-term follow-ups are required to ensure the best possible outcome.


The effects of psychoeducation and motivational interviewing on treatment adherence and functionality in individuals with bipolar disorder.
Individuals diagnosed with bipolar disorder (BD) encounter difficulties in adherence to treatment and functionality. Although it is known that psychosocial interventions such as motivational interviewing (MI) and psychoeducation are important in regard to improving adherence to treatment and functionality, the content and nature of these interventions remain uncertain. This study was conducted to determine the effects of psychoeducation and MI on treatment adherence and functionality in individuals diagnosed with BD. In this study, a quasi-experimental pretest-posttest design with three groups was adopted. The study was completed with 119 participants in the MI (n = 32), psychoeducation (n = 31), and control (n = 56) groups. There was a statistically significant improvement in the psychoeducation and MI groups in terms of treatment adherence compared to the control group (F = 32.672, p = 0.001, Partial η2 = 0.364). Similarly, the psychoeducation and MI groups had significantly higher functionality levels compared to the control group, and significant differences were observed between the groups regarding the degree of improvement in functionality dimensions including the feeling of stigmatization (F = 8.433, p = 0.001, Partial η2 = 0.129) and participation in social activities (F = 7.038, p = 0.001, Partial η2 = 0.110). It can be stated that psychoeducation and MI have positive effects in terms of improvement in treatment adherence and functionality in individuals diagnosed with BD.


Smoking and gastrointestinal cancer patients-is smoking cessation an attainable goal?
Negative consequences of tobacco use during cancer treatment are well-documented but more in-depth, patient-level data are needed to understand patient beliefs about continued smoking (vs cessation) during gastrointestinal (GI) cancer treatment. We conducted semi-structured interviews with 10 patients who were active smokers being treated for GI cancers and 5 caregivers of such patients. All interviews were audio-recorded, transcribed verbatim, and uploaded to NVivo. We consensus coded data inductively using conventional content analysis and iteratively developed our codebook. We developed data matrices to categorize the themes regarding patient perspectives on smoking as well as presumed barriers to smoking cessation during active therapy. Our interviews revealed three consistent themes: (a) Smoking cessation is not necessarily desired by many patients who have received a cancer diagnosis; (b) Failure in past quit attempts may lead to feelings of hopeless about future attempts, especially during cancer treatment; (c) Patients perceived little to no access to smoking cessation treatment at the time of their cancer diagnosis. Well-designed systemic changes that promote the positive and efficacious effects of quitting smoking during cancer treatment, and that provide barrier-free access to such treatments may be helpful in promoting tobacco-free behavior during cancer treatment.


Comparison of cardiovascular response between patients on warfarin and hypertensive patients not on warfarin during dental extraction.
To evaluate cardiovascular response in patients on warfarin and hypertensive patients not on warfarin during dental extraction. This retrospective study included 53 patients who had undergone dental extraction while on warfarin (mean age 78.8 ± 6.3 years, 26 men) and 66 with hypertension who had undergone dental extraction but were not on warfarin (mean age 77.4 ± 6.8 years, 22 men). Vital signs were monitored in both groups during extraction. The highest systolic blood pressure (SBP) values (mean 150.1 ± 21.1 mmHg) were observed in patients on warfarin before (9.0%) and after (10.3%) administration of local anesthesia (LA), during extraction (39.7%), and during (33.3%) and after (7.7%) suturing (n = 78; p < 0.01), and in hypertensive patients not receiving warfarin (160.6 ± 24.8 mmHg) before (19.2%) and after (27.3%) administration of LA, during extraction (29.3%), and during (18.2%) and after (6.1%) suturing (n = 99; p < 0.01). The highest SBP was linearly correlated with SBP before administration of LA in patients on warfarin (highest SBP = 0.9415 × SBP before LA + 23.243, R2 = 0.75481) and in hypertensive patients not on warfarin (highest SBP = 1.0027 × SBP before LA + 15.789, R2 = 0.60341). The highest SBP was not distributed evenly between patients on warfarin and hypertensive patients not on warfarin during dental extraction and was strongly associated with SBP before LA regardless of anticoagulant status. Thorough management of SBP is required in patients on warfarin to avoid thromboembolism and major hemorrhagic complications. Knowing the SBP value before dental treatment would help predict the risk of cardiovascular complications.


Recombinant human activated protein C.
This review will summarise the relevant pathophysiology of sepsis, the rationale for treatment with recombinant human activated protein C and the evidence for and against its use, and will provide evidence-based recommendations for its administration.


Second primary breast cancer after unilateral mastectomy alone or with contralateral prophylactic mastectomy.
An increasing number of patients undergo contralateral prophylactic mastectomy (CPM) for unilateral breast cancer. However, the benefit of CPM has not been quantified in the setting of contemporary breast cancer therapy. We performed an analysis of 180 068 patients in the Surveillance, Epidemiology, and End Results (SEER) database, diagnosed with unilateral ductal breast carcinoma between 1998 and 2013 and treated with unilateral mastectomy (UM) or CPM. UM was performed in 146 213 patients (81.2%); CPM was performed in 33 855 patients (19.8%). Primary outcome of interest was cumulative incidence of a second primary breast cancer in the ipsilateral or contralateral breast greater than 3 months after initial diagnosis. Cumulative incidence analysis was based on a Cox proportional model to generate curves of second primary breast cancer in any breast, ipsilateral breast only, or contralateral breast only. Patients who underwent CPM had a significantly reduced incidence of second primary breast cancer 10 and 15 years after surgery (CPM 0.93% [0.73%, 1.12%] vs UM 4.44% [4.28%, 4.60%]). Patients who underwent CPM had significantly lower adjusted hazard of second primary breast cancer when compared with UM (HR 0.38 vs 1.0, P < .0001). CPM offers some protection from a second primary breast cancer, attributable to a reduced incidence in the contralateral breast. These findings provide additional information to providers and patients as they make decisions regarding surgical management. They should also be interpreted in the context of the absolute incidence of second primary breast cancer after UM and previous literature demonstrating no survival benefit.


Risk Factors for Mortality in Mechanically Ventilated Patients with COVID-19 in a Mississippi Community Health System.
To evaluate differences between survivors versus nonsurvivors undergoing mechanical ventilation for coronavirus disease 2019 (COVID-19)-associated respiratory failure at two community medical centers. This was a multicenter, retrospective cohort analysis of all adult patients mechanically ventilated for COVID-19-associated respiratory failure in two community hospital intensive care units in southern Mississippi from March 15, 2020 through October 10, 2020. Among 56 patients requiring mechanical ventilation, the mortality rate was 75% (42/56). Expired patients were intubated later (2 vs 5 days, 95% confidence interval [CI] 6.314-0.8041, P = 0.0983), had lower PaO2:FiO2 ratios (65 vs 77.5 mm Hg, 95% CI 36.08-59.03, P = 0.6305), and tolerated lower levels of positive end-expiratory pressure (7.9 vs 12.6 cm H2O, 95% CI 0.1373-6.722, P = 0.0415) at the time of intubation. Our results suggest that earlier intubation may be associated with reduced mortality in patients with COVID-19-associated respiratory failure and should be further evaluated in the form of a randomized controlled trial.


Germline BRCA1 and BRCA2 mutations and the risk of bladder or kidney cancer in Poland.
The role of the BRCA1 and BRCA2 genes in bladder and renal tumorigenesis is unclear. Our goal was to determine the prevalence of specific founder mutations genes BRCA1 (5328 insC, C61G and 4153 delA) and BRCA2 (C5972T) mutations in bladder and kidney cancer patients from Poland. We genotyped 1028 patients with bladder cancer and 688 cases with kidney cancer and two control groups. A BRCA1 mutation (all variants combined) was detected in peripheral blood leukocytes in 5 out of 1028 (0.5%) bladder cases and in 17 of 4000 controls (0.4%) (odds ratio [OR], (OR = 1.1; 95% CI 0.42-3.11; p = 1.0). Among 688 unselected kidney cancer cases a BRCA1 mutations was reported in three patients (0.4%) (OR = 1.0; 95% CI 0.29-3.51; p = 1.0). The mutation C5972T in BRCA2 was observed in 54 bladder cancer patients (5.2%) and in 159 of 2791 healthy controls (5.7%) (OR = 0.9; 95% CI 0.66-1.26; p = 0.6). Fifty kidney cancer cases carried a BRCA2 mutation (7.3%) (OR = 1.3; 95% CI 0.93-1.80; p = 0.1). In conclusion, we found no difference in the prevalence of BRCA1 and BRCA2 founder mutations between cases and healthy controls. The mutations BRCA1 and BRCA2 seem not to play a role in bladder and kidney cancer development in Polish patients.


[Interpretation of paced ECGs by the wearable defibrillator : Pitfalls and solutions].
The wearable cardioverter defibrillator (WCD) can protect patients against sudden cardiac death during temporarily increased or unknown risk of ventricular arrhythmias or in the situation of implantable cardioverter-defibrillator (ICD) explantation due to infection. In unusual cases, misinterpretation of the ECG by the tachycardia detection and discrimination algorithm of the WCD can occur which can lead to inappropriate acoustic alerts or inappropriate WCD therapy. We explain the mechanisms of inappropriate WCD therapy in two cases from daily clinical practice together with potential strategies to avoid such events in this special group of patients.


Angiographic evidence of progressive lumen narrowing over 2 years following drug-eluting stent implantation.
Questions persist regarding the ability of drug-eluting stents (DES) to inhibit intimal growth in the long-term. We prospectively enrolled 766 lesions treated with DES that underwent angiographic examination at 6 months and 2 years after stenting. Lesions with 6-month restenosis (>50% of visual stenosis) were excluded. The primary end point was quantitative change in minimal lumen diameter (MLD) according to serial angiography of the segment (in-segment), the stented region (in-stent) and both edges. Late loss, defined as MLD change, was categorized as early (between post-procedure and 6 months), delayed (between 6 months and 2 years), or overall (between post-procedure and 2-years). MLD progressively decreased in both the in-stent and edge regions at both 6 months and 2 years (p<0.001 in all paired analyses). In-segment MLD decreased from a median 2.27 mm (interquartile range; 1.98, 2.62) at post-procedure to 2.18 mm (1.86, 2.47; p < 0.001 with post-procedure) at 6 months, and to 2.02 mm (1.66, 2.37; p<0.001 with 6 months) at 2 years. Late loss was 0.0 6 mm (-0.05, 0.26) in the early phase, 0.09 mm (-0.01, 0.28) in the delayed phase, and 0.20mm (0.03, 0.50) overall. Two-year angiographic restenosis occurred in 54 (7.0%) lesions, and 65 (8.5%) underwent target lesion revascularization over a median follow-up of 52.5 months. Serial angiographic analysis showed that DES lumen diameter progressively narrowed over 2 years post-procedure. However, the incidence of target lesion revascularization was relatively low due to the small amount of late loss in the delayed phase.


Management of intrinsic spasticity in the hand with phenol injection or neurectomy of the motor branch of the ulnar nerve.
Thirty-nine adults with acquired spastic disorders who had 21 phenol injections and 21 neurectomies of the motor branch of the ulnar nerve in Guyon's canal for control of intrinsic spasticity in the hand were reviewed. Follow-up averaged 25.8 months for the patients with phenol blocks and 24.3 months for those who had a neurectomy. Intrinsic spasticity was relieved in all hands postoperatively. After the phenol block, which is a temporizing procedure, 13 hands had return of spasticity in 6 months. Eight hands had little or no return of spasticity and required no further treatment. Neurectomy was performed in predominantly nonfunctional hands with severe hygiene problems and with no potential for further neurologic recovery. Hand function was improved in six hands after phenol block and in one hand after neurectomy. Hygiene was improved in all hands after phenol block and in all except one hand after neurectomy. Two wound infections and one wound dehiscence occurred.


The effects of polymers on the shrinkage temperature of tendon.
The shrinkage temperature of tendon increases in the presence of a variety of polymers, both charged and uncharged. Using poly(ethylene glycol)s and carbohydrates of varying size, an effective radius of approx. 0.6 nm was found to be the minimum size required to achieve maximum stabilization. Above this minimum size, variations in solute size had little effect. Smaller solutes lowered the shrinkage temperature of tendon by disrupting the fibrillar structure. The study demonstrates that stabilization occurs when the solute is excluded from the fibrils and does not appear to require binding of the solute and collagen.


Isolation, propagation, and HIV-1 infection of monocyte-derived macrophages and recovery of virus from brain and cerebrospinal fluid.
Mononuclear phagocytes (MP: monocytes, dendritic cells, and tissue macrophages) are host cells for the human immunodeficiency viruses types 1 and 2. MPs are both the first lines of defense and vehicles for viral dissemination in the infected human host. Viral infection of MP can affect the disease directly during interstitial pneumonitis and HIV encephalitis. Both revolve around MP secretions of immune regulatory and neurotoxic factors. Clearly, laboratory models that mimic disease need to include primary human MP infected with viral isolates obtained from diseased tissues. Over the past two decades our laboratory has developed state-of-the-art methods for isolation and propagation of monocytes from peripheral blood. This technology directly supports work at the University of Nebraska Medical Center as well as research performed throughout the United States, including the laboratories of Drs. Mario Stevenson, William Tyor, David Volsky, Loyda Melendez, and Mary-Jane Potash, among others. The importance of these cells as targets for virus and reservoirs of persistent infection are discussed.


Assessment of the pollution potential of a special case of abandoned sulfide tailings impoundment in Riotinto mining district (SW Spain).
This work describes a special case of pollution potential assessment applied to an abandoned sulfide tailings impoundment located in the Riotinto mining district (Huelva), near the Tinto River. Three overlapping levels of discharged tailings were recognized in the impoundment, from deeper to upper: pale yellow to white, red, and brownish-yellow. Mineralogical, physical, and chemical characteristics of tailings, water leachates, water, and sulfate efflorescent salts were analyzed. The total toxic element content and the leachate concentration were respectively used to calculate two indices that support potential toxicity assessment: the Index of Contamination (IC) and the Hazard Average Ratio (HAQ). According to the IC values, all tailings samples showed a high potential for contaminating soils and sediments, especially the intermediate tailings with up to As (8.6 g kg-1), Pb (14.8 g kg-1), and Cu (1 g kg-1). Deeper tailings leachate was extremely saline and acidic, with a very high concentration of sulfates and toxic elements, exceeding the values: 2600, 980, 30, and 17 mg L-1 for SO4, Fe, Al, and Cu, respectively. For this reason, these deeper tailings were linked to the saline and acid seepage, and also to the sulfate acid efflorescences formed at the dike toe. In conclusion, the studied abandoned tailings impoundment is related with a high likelihood of polluting the environment, represented by very high IC and HAQ values. However, when the Tinto River is considered the receiving water body, the severity of the potential contamination must be judged as very low.


Management of recurrent adhesion after vaginal recanalization surgery by using interdigitating Y-flap technique: Case series.
Adhesion is one of complication after vaginal recanalization surgery that occurs due to the free tissue attached during the wound healing process and should be treated carefully. Otherwise, it will become obstruction to the vagina and lead to hematocolpos. The chosen techniques should prevent recurrent adhesion, synechia or stenosis. In this case series, we performed interdigitating Y-flap technique for managing recurrent synechiae post recanalization vaginal surgeries to prevent future stenosis. The first case was a 16 years old teenager, complained not menstruating and abdominal pain. Patient already had recanalization vagina surgery for correcting distal vaginal agenesis two years ago. After that, patient already had menstruation. There were hematometra, hematocolpos and vaginal adhesion from examination. The second case was a 12 years old teenager, complained having slight blood menstruation after septum excision surgery. From the examination, there was stenosis vagina at 3 cm proximal from hymenal ring. Both patients were treated by interdigitating Y-flap surgery for correcting the synechiae. After follow up treatment, there was no complaint from patients. Both patients were having synechia post vaginal recanalization surgery. To prevent recurrent synechiae, we decided to do interdigitating Y-Flap technique for correcting synechiae. With this technique, the scar tissue may not develop contractured scar and narrowing vagina. Interdigitating Y-Flap technique may become an option for managing complex recurrent adhesion, synechia or stenosis. This technique is simple, easier and reduces the risk of stenosis in the future with better scar formations.


Physiological and metabolic aspects of very prolonged exercise with particular reference to hill walking.
Hill walking is a popular recreational activity in the developed world, yet it has the potential to impose severe stress simultaneously upon several regulatory systems. Information regarding the physiological strain imposed by prolonged walking outdoors in adverse climatic conditions was reported almost four decades ago and recent research has extended some of this work. These data indicate that once the walker fatigues and starts to slow or stops walking altogether, the rate of heat production falls dramatically. This decrease alone predisposes to the development of hypothermia. These processes, in adverse weather conditions and/or during periods when the level of exertion is low (with low heat production), will be accelerated. Since the majority of walkers pursue this activity in groups, the less fit walkers may be more susceptible to fatigue when exercising at a higher relative intensity compared with their fitter counterparts. The best physiological offset for hypothermia is to maintain heat production by means of exercise, and so fatigue becomes a critical predisposing factor; it is as important to facilitate heat loss, especially during periods of high exertion, as it is to maintain heat production and preserve insulation. This can be partly achieved by clothing adjustments and consideration of the intensity of exercise. Failure to provide adequate energy intake during hill walking activities has been associated with decreased performance (particularly with respect to balance) and impaired thermoregulation. Such impairments may increase susceptibly to both fatigue and injury whilst pursuing this form of activity outdoors. The prolonged low to moderate intensity of activity experienced during a typical hill walk elicits marked changes in the metabolic and hormonal milieu. Available data suggest that during hill walking, even during periods of acute negative energy balance, blood glucose concentrations are maintained. The maintenance of blood glucose concentrations seems to reflect the presence of an alternative fuel source, a hormonally induced increase in fat mobilisation. Such enhancement of fat mobilisation should make it easier to maintain blood glucose by decreasing carbohydrate oxidation and promoting gluconeogenesis, thus sparing glucose utilisation by active muscle. During strenuous hill walking, older age walkers may be particularly prone to dehydration and decreased physical and mental performance, when compared with their younger counterparts. In summary, high rates of energy expenditure and hypohydration are likely to be closely linked to the activity. Periods of adverse weather, low energy intake, lowered fitness or increased age, can all increase the participants' susceptibility to injury, fatigue and hypothermia in the mountainous environment.


Do we need a contact tracing app?
The goal of this paper is to shed some light on the usefulness of a contact tracing smartphone app for the containment of the COVID-19 pandemic. We review the basics of contact tracing during the spread of a virus, we contextualize the numbers to the case of COVID-19 and we analyze the state of the art for proximity detection using Bluetooth Low Energy. Our contribution is to assess if there is scientific evidence of the benefit of a contact tracing app in slowing down the spread of the virus using present technologies. Our conclusion is that such evidence is lacking, and we should re-think the introduction of such a privacy-invasive measure.


No Effect of Different Stimulation Conditions on Verbal Fluency and Visuospatial Orientation in Patients with Subthalamic Nucleus Deep Brain Stimulation.
Subthalamic nucleus deep brain stimulation is an effective treatment for the symptomatic treatment of Parkinson's disease. Apart from the obvious motor benefits, some cognitive side effects have been reported, particularly in verbal fluency. Our aim was to evaluate the effects of the stimulation on verbal fluency and visuospatial orientation with changing stimulation conditions in 35 patients with Parkinson's disease. Patients were randomized for their stimulation conditions as 'both on', 'both off', 'right on', and 'left on' and underwent verbal fluency and visuospatial orientation tasks during their drug-on periods. Letter and categorical fluency tasks and Benton's Judgment of Line Orientation Test were used for assessment. Overall, 6 patients were excluded due to dementia or depression. For verbal fluency, the number of words they produced in 1 min was similar in four stimulation conditions (p > 0.05). No significant difference was found between stimulation conditions in the spatial orientation task. We were unable to find any significant changes in verbal fluency and visuospatial orientation task scores with different stimulation conditions. This result suggests that either stimulation has no effect on given domains or the effect is so small that more detailed batteries are required to detect the difference.


Infection risk assessment of diarrhea-related pathogens in a tropical canal network.
A quantitative microbial risk assessment (QMRA) of Cryptosporidium, Giardia and diarrhegenic Escherichia coli (DEC) infection was performed using Monte Carlo simulations to estimate the human health risks associated with the use of canal water for recreational purposes, unrestricted and restricted irrigation in a tropical peri-urban area. Three canals receiving municipal, agricultural, and, predominantly, industrial wastewater were investigated. Identification of pathogenic protozoans revealed the major presence of Cryptosporidium hominis and both assemblages A and B of Giardia lamblia. The highest individual infection risk estimate was found to be for Giardia in an exposure scenario involving the accidental ingestion of water when swimming during the rainy season, particularly in the most polluted section, downstream of a large wholesale market. The estimated annual risks of diarrheal disease due to infection by the protozoan parasites were up to 120-fold greater than the reported disease incidence in the vicinity of the studied district and the entire Thailand, suggesting a significant host resistance to disease beyond our model's assumptions. In contrast, annual disease risk estimates for DEC were in agreement with actual cases of diarrhea in the study area.


Identifying the early 2000s hiatus associated with internal climate variability.
This study focuses on re-examining the early 2000s hiatus and the associated key components of the global mean surface temperature (GMST) using multiscale statistics for five well-known gridded surface temperature and two reanalysis datasets. The hiatus is characterized as a near-zero trend on the decadal scale corresponding to the maximum P-value via an F-test in statistics. The results reveal that the hiatus exists in both the GMST and global mean air temperature (GMAT) time series, rather than in global warming component, which has maintained an approximately constant rate of change of approximately 0.08 °C/decade over the past three decades. The hiatus's duration is different from that of time series such as 2002-2012/2001-2013/2002-2014 in HadCRUT4, NOAA-old, ERA-Interim and NCEP-R2. The newly gridded datasets with data infilling or bias correction for interpreting the sea surface temperature (SST) measurement from the old versions show a slightly higher trend from 2002-2012 than the hiatus, which is thus regarded as a slowdown. Comparison suggests that the hiatus should be during the period 2002-2012. Orthogonal wavelet decomposition of the temperature time series shows that the hiatus was merely a decadal balance between cooling from interannual variability and global warming, in addition to weak warming from interdecadal and multidecadal climate oscillations. In addition, the evolutions of the GMST's interannual composites are well coincided with Niño3.4 SST anomalies, which is consistent with the numerical simulation performed by Kosaka and Xie in 2013. Hence, it is the anomalous El Niño Southern Oscillation (ENSO) events in the early 2000s that caused the hiatus despite a constant rate of global warming and the maximum magnitude of the multidecadal composite that led to the limited contribution to the trend during this period. The multidecadal composite follows a downward path, which implies that future climate conditions will likely rely on competition between multidecadal cooling and global warming if the multidecadal climate cycle repeats, as was experienced during the second half of the twentieth century.


Pain: The agony and the AstC.
Pain serves critical biological functions, but under some circumstances it is best suppressed. A new study identifies a channel, a neuropeptide, and a pair of neurons in the fly brain that suppress pain.


Activation of XBP1 but not ATF6α rescues heart failure induced by persistent ER stress in medaka fish.
The unfolded protein response is triggered in vertebrates by ubiquitously expressed IRE1α/β (although IRE1β is gut-specific in mice), PERK, and ATF6α/β, transmembrane-type sensor proteins in the ER, to cope with ER stress, the accumulation of unfolded and misfolded proteins in the ER. Here, we burdened medaka fish, a vertebrate model organism, with ER stress persistently from fertilization by knocking out the AXER gene encoding an ATP/ADP exchanger in the ER membrane, leading to decreased ATP concentration-mediated impairment of the activity of Hsp70- and Hsp90-type molecular chaperones in the ER lumen. ER stress and apoptosis were evoked from 4 and 6 dpf, respectively, leading to the death of all AXER-KO medaka by 12 dpf because of heart failure (medaka hatch at 7 dpf). Importantly, constitutive activation of IRE1α signaling-but not ATF6α signaling-rescued this heart failure and allowed AXER-KO medaka to survive 3 d longer, likely because of XBP1-mediated transcriptional induction of ER-associated degradation components. Thus, activation of a specific pathway of the unfolded protein response can cure defects in a particular organ.


Bilateral adhesive capsulitis following influenza vaccination: A case report.
Bilateral shoulder adhesive capsulitis may develop in association with the administration of an influenza vaccine. Vaccine administration should utilize proper technique to avoid injection into the shoulder capsule.


Complications of chronic otitis media with cholesteatoma during a 10-year period in Kosovo.
We review and discuss the results of treatments for complications of cholesteatomatous chronic otitis media (CCOM) in a tertiary health care center. In a retrospective study, the medical records of patients with complications of CCOM who had undergone surgical treatment at the ENT Clinic of the University Clinical Center of Kosovo for the period 1994-2004 were reviewed. From a total of 1,803 patients suffering from CCOM, in 91 patients, 55 (60.4%) men and 36 (39.6) women, one or two complications are recorded. The mean age of the subjects was 30 years, and the age range was from 1 to 76 years. Extracranial (EC) complications were observed in 52 cases (57.1%), and intracranial (IC) complications were seen in 29 patients (31.9%). Twelve patients (11%) had multiple complications. For the EC cases, we found that subperiostal mastoidal abscess occurred in 26% of the all patients, facial nerve palsy was seen in 16.48% and labyrinthine fistula occurred in 10%. For the IC cases, meningitis (19.7%) and perisinusal abscess (15.3%) were the most common complications. The most often isolated pathogen from ear swabs was Proteus mirabilis in 33.3% of cases. The most frequent radiological diagnostic procedures were mastoid tip X-rays, which were performed in 77% of the patients, and computed tomography in 24%; magnetic resonance imaging was not performed on any of the patients during the study period. Patients with EC complications were treated in the ENT Clinic, whereas patients with IC complications, after otologic surgical procedures, were transferred to the Neurosurgery Clinic or to the Clinic for Infectious Diseases. In this series, three patients (3.3%) died as a result of complications, while the remaining 96.7% survived. Complications of COM with cholesteatoma can represent life-threatening conditions, and close cooperation between otosurgeons, neurosurgeons and infectious disease specialists is mandatory.


The usability and ergonomics of axes.
This study evaluated the ergonomics and usability of axes. Several methods were used, namely measurement of impact velocity, the determination of kinetic energy, splitting performance tests, durability tests of blades and handles, and user trials. The mean velocity used in the striking was 9.6m/s (8.9-10.3m/s, SD 1.5). In the durability tests, the blades withstood the test reasonably well. In the bending tests, there were differences in the durability of the handles, which related to their material. A wide variation in the durability of the axe handles was also observed. User trials were conducted to evaluate the various features of the axes.


Procalcitonin measurement for detection of serious bacterial infection in febrile children: comparison between two automated immunoassays.
To assess the concordance of procalcitonin values at 3 cut-off ranges in a cohort of pediatric samples presenting with fever without source, using two different automated immunoassays. 65 frozen samples from children presenting with fever without source were thawed, tested on both Kryptor and VIDAS systems, and compared using a regression analysis, a Bland-Altman difference plot, and analysis of concordance at the clinically relevant cut-off points. Kryptor and VIDAS PCT results correlated remarkably well (r=0.952), with no significant difference in the frequency distribution over the 3 cut-off ranges (p=0.1384). The strength of the agreement was good (κ=0.759) with an overall concordance of 84.6%. Correlation and concordance of PCT values measured by both systems were good. This finding allows clinical implementation of both techniques with the same nominal PCT cut-off values for detection of serious bacterial infection in children presenting with fever without source.


Thrombolysis in an Acute Ischemic Stroke Patient on Direct Anticoagulant Therapy Outside of the Traditional Time Window: A Case Report.
A stroke is a life-threatening medical condition that could be disabling if left untreated. Intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) can be effective when initiated in an acute stroke, but their benefit is time-dependent and their use may be restricted by contraindications (CIs) such as anticoagulation therapy. The critical therapeutic time window, which was previously limited to 4.5-6 hours, is now extended to 24 hours in selected patients due to the development of advanced neuroimaging techniques. Herein, we discuss the case of a 50-year-old patient on rivaroxaban who developed acute ischemic stroke (AIS) and was treated successfully with intravenous recombinant tissue plasminogen activator thrombolysis more than six hours after the time he was last seen well (LSW). Our case demonstrates the importance of advanced neuroimaging techniques in identifying AIS candidates for IVT and/or MT with late or unknown time windows as well as the importance of case-by-case assessment when challenged by theoretical contraindications for thrombolysis.


Kummel disease treatment by unipedicular vertebral augmentation using curved injection cannula.
This study was designed to evaluate the efficacy of the blunt-tipped curved injection needle (BCN) AVAflex (Care Fusion) for vertebral augmentation in cases of Kummel's disease. We performed 25 vertebral augmentation procedures on 25 consecutive patients (11 men/14 women; mean age, 67 years) with Kummel's disease using the blunt-tipped curved injection needle with PMMA cement. We performed all 25 procedures by unipedicular left approach with patients in prone position under local anesthesia and mild sedation. In all cases, an intravertebral cleft was evident on preprocedural imaging. We evaluated pain intensities by Visual Analogic Scale (VAS) before and at first day, 6 months, and 1 year after procedure. In all cases the curved injection cannula permitted the filling of the clefts and surrounding cancellous bone without any complication. A significant reduction of kyphotic deformities of the treated vertebral bodies was evident. A significance decrease in VAS values at 1 year also was evident (mean decrease 7.2). At plain dynamic postprocedural X-rays checks, there was no sign of pathologic intravertebral motion as evidence of optimal stabilization. BCN AVAflex is a safe and effective device for targeted vertebral augmentation in cases of Kummel's disease. Its distinctive characteristic is the curved injection cannula, which enables targeting the cement injection to areas far off the trajectory of the straight access cannula, thus providing excellent cement spread throughout the entire volume of vertebral body.


Intercalating, cytotoxic, antitumour activity of 8-chloro and 4-morpholinopyrimido [4',5':4,5]thieno(2,3-b)quinolines.
Circular dichroism, hydrodynamic methods, absorbance and fluorescence titration's were employed to study the interaction of 8-chloropyrimido[4',5':4,5]thieno(2,3-b)quinolin-4(3H)-one (chloro-PTQ) and 4-morpholinopyrimido[4',5':4,5]thieno(2,3-b)quinoline (morpholino-PTQ) with DNA. The association constant of chloro-PTQ and morpholino-PTQ were of the order of 10(5) and 10(6) M(-1). The fluorescence properties at ionic strength of 10mM are best fit by the neighbor exclusion model, with Ki of 0.3 x 10(4) M(-1) to 3.2 x 10(6) M(-1). CD spectra indicate that stacking of these compounds with DNA induces strong helicity in the usually disordered structure of the double strand. Viscosity experiments with sonicated rod like DNA fragments, produced a calculated length of 2.4A/bound of chloro/morpholino-PTQ molecule. The binding of chloro/morpholino-PTQ to DNA increased the melting temperature by about 1.5-7.0 degrees C. The cytotoxicity of these compounds on K-562, HL-60, Colo-205 and B16F10 melanoma are quite similar and IC(50) was in the range of 1.1-8muM. The anticancer efficacy against B16F10 melanoma has provided evidence of major anticancer activity for morpholino-PTQ. Single or multiple i.p. doses of compounds showed high level of activity against the subcutaneous (s.c.) grafted B16 melanoma with a significant increase in life span (161% and 272%). The aim of this study was to analyze the physicochemical properties of the chloro/morpholino-PTQ in an attempt to understand their superior biological activity. This research offers a new intercalation functional group to DNA targeted drug design.


Adenosine metabolism in human whole blood. Effects of nucleoside transport inhibitors and phosphate concentration.
Adenosine (Ado, 10 microM) was metabolized in whole blood within 1 min, primarily to hypoxanthine and ATP. The concentration of Ado, the activities of adenosine deaminase (ADA) and Ado kinase, the Km values for Ado with ADA and Ado kinase, and the substrate inhibition of Ado kinase are factors that govern the Ado metabolism between deamination and phosphorylation. If ADA activity was blocked by 2'-deoxycoformycin (dCF, 5 microM), a tight-binding inhibitor of ADA, most of the Ado (96%) was incorporated into adenine nucleotides, whereas if Ado kinase activity was blocked with 5-iodotubercidin (10 microM), Ado was mainly (95%) metabolized into hypoxanthine. A high phosphate concentration (25 mM) caused marked increases in the formation of IMP. The nucleoside transport inhibitors dilazep (1 microM), dipyridamole (10 microM) and nitrobenzylthioinosine (NBMPR, 1 microM) strongly blocked cellular Ado metabolism. In the presence of nucleoside transport inhibitors, Ado which slowly enters the cell was metabolized principally by Ado kinase rather than ADA. Dilazep, NBMPR and dipyridamole were more effective in blocking Ado uptake and metabolism by erythrocytes suspended in a protein-free medium than by cells suspended in plasma.


Prognostic Analysis and Biomarkers Identification of Immune Infiltration in Early and Late Stage Hepatocellular Carcinoma Based on TCGA Data.
Hepatocellular carcinoma (HCC) is a major cause of cancer death in the world. The aim of this study was to establish a new model to predict the prognosis of HCC. The mRNA, miRNA and lncRNA expression profiles of early (stage I-II) and late (stage III-IV) stage HCC patients were acquired from The Cancer Genome Atlas (TCGA) database. The differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs) and lncRNAs (DElncRNAs) were identified between early and late stage HCC. Key molecules associated with the prognosis, and important immune cell types in HCC were identified. The nomogram based on incorporating age, gender, stage, and all important factors was constructed to predict the survival of HCC. A total of 1516 DEmRNAs, 97 DEmiRNAs and 87 DElncRNAs were identified. A DElncRNA-DEmiRNA-DEmRNA regulatory network including 78 mRNAs, 50 miRNAs and 1 lncRNA was established. Among the regulatory network, 11 molecules were significantly correlated with the prognosis of HCC based on Lasso regression analysis. Then, Preadipocytes and 3 survival-associated DEmRNAs were identified as crucial biomarkers. Subsequently, a nomogram with a differentiation degree of 0.758, including 1 immune cell, 11 mRNAs and 3 miRNAs, was generated. Our study constructed a model by incorporating clinical information, significant biomarkers and immune cells to predict the survival of HCC, which achieved a good performance.


Preliminary findings in the neurophysiological assessment of intercostal nerve injury during thoracotomy.
Previous work has suggested that intercostal nerve injury is a major factor in the aetiology of chronic post-thoracotomy pain. The aim of this study was to establish if there was identifiable intercostal nerve injury during thoracotomy. Intercostal nerves were stimulated and motor evoked potentials were recorded from intercostal muscles in 13 patients undergoing thoracotomy. Measurements were taken before and after entering the pleural space, after removal of the rib retractor and after intercostal space closure. Intercostal nerves functioned normally before and after entering the pleural space. After the rib retractor was removed, there was a total conduction block in the nerve immediately above the incision in every patient. In the nerves above this, six had a total block, one a partial block and three had normal conduction. There was a total conduction block in the nerve immediately below the incision in all but one patient. Of the nerves below this, four had a total block, two a partial block and three had normal conduction. In the cases of total conduction block, there was either a discrete block at the level of the distal end of the rib retractor or impairment throughout the whole nerve. Intercostal space closure did not injure any previously uninjured nerve. In a solitary patient where rib retraction was not employed, there was no impairment of the intercostal nerves throughout the operation. This study demonstrates for the first time that intercostal nerve injury occurs routinely due to rib retraction during thoracotomy. We believe that it may be an important step toward understanding the cause of post-thoracotomy neuralgia.


A complementary learning approach for expertise transference of human-optimized controllers.
In this paper, a complementary learning scheme for experience transference of unknown continuous-time linear systems is proposed. The algorithm is inspired in the complementary learning properties that exhibit the hippocampus and neocortex learning systems via the striatum. The hippocampus is modelled as pattern-separated data of a human optimized controller. The neocortex is modelled as a Q-reinforcement learning algorithm which improves the hippocampus control policy. The complementary learning (striatum) is designed as an inverse reinforcement learning algorithm which relates the hippocampus and neocortex learning models to seek and transfer the weights of the hidden expert's utility function. Convergence of the proposed approach is analysed using Lyapunov recursions. Simulations are given to verify the proposed approach.


Digital Technology Redefining Implant Therapies: Two Case Reports.
Providing clinicians with comprehensive tools to transform the smiles of their patients, digital applications are wholly changing the dental profession. The impact of technology on the delivery of care has enabled clinicians to be increasingly more analytical and meticulous in planning and rigidly focused on the predictability of outcomes. Tools are available that allow clinicians to better understand their patients, not only anatomically and biomedically, but with regard to their personal goals for their oral care. This article highlights some of the more profound technological advancements clinicians have at their disposal to both plan and deliver streamlined minimally invasive treatment that equals or exceeds historically cutting-edge esthetic dentistry. The case studies presented indicate how professional collaboration and prosthetically driven planning may be utilized to achieve lofty goals for patient satisfaction, even in highly complex and challenging cases.


Aortic size and aortic calcification. A necropsy Study.
Measurements of aortic length and circumference in 336 post-mortem specimens confirm earlier, neglected observations on the progressive increase in aortic size which occurs with advancing years. The increase is not related to atherosclerosis , or to hypertension and seems to be part of a true ageing process. The value of measurement of aortic size in body age determination merits exploration by forensic pathologists. Aortic calcification is found in raised and complicated atherosclerotic plaques and its prevalence and severity closely follows the accepted pattern of plaque severity, occurring earlier and more severely in men, in the abdominal aorta and in patients with overt vascular disease in other territories such as patients with cardiac infarcts. No association was found between the amount of calcification and the presence of hypertension, diabetes or neoplasia.


Frequency of consumption of foods rich in calcium and vitamin D among school-age children.
Calcium is one of the most important minerals for the human body which is essential for healthy bones and teeth. Vitamin D has hormone-like properties in the human body. It is supplied with the diet, but it is also synthesized by the body under exposure to UV radiation. Vitamin D controls calcium and phosphorus metabolism and is responsible for bone modeling and mineralization. The objective of this study was to evaluate eating habits and food preferences of school-age children meet the demand for calcium and vitamin D, and estimate the frequency of consumption of foods rich in these nutrients. A total of 197 parents of 7- to 9-year-olds attending randomly selected primary schools in Lublin and Świdnik were asked to fill out a questionnaire designed by the authors. The results were processed by the Chi-squared test in the Excel application. Considerable differences in the consumption of milk and dairy products were observed between age groups. In the group of 7-year-olds, 57.5% of children drank milk and ate dairy products at least once a day, whereas in the group of 9-year-olds, only 16.6% of children ate dairy products at least once a day. The intake of foods rich in vitamin D was equally low among the surveyed children. School-age children may be at risk of calcium and vitamin D deficiencies due to low consumption of milk, dairy products and fish, and inadequate vitamin D supplementation. Parents should be educated about nutrition to change the family's eating habits.


Hereditary xanthinuria in 2 Pakistani sisters: asymptomatic in one with beta-thalassemia but causing xanthine stone, obstructive uropathy and hypertension in the other.
We describe a 3-year-old Pakistani girl who presented with recurrent urinary infections. She had a nonfunctioning hydronephrotic right kidney and hypertension. At operation a calculus was impacted in the right ureter with dilatation of the pelviocaliceal system. Nephrectomy was performed. Histology revealed end stage pyelonephritis. The calculus consisted of pure xanthine. Further investigations demonstrated low serum uric acid and absent urinary uric acid with increased excretion of xanthine. Eight months after nephrectomy blood pressure had decreased to normal. Her 5-year-old sister, who has beta-thalassemia, also has a low serum uric acid concentration and xanthinuria. The treatment of choice is to increase fluid intake so that the urine xanthine concentration remains below the level at which xanthine crystallizes. This may require adjustment of the urine pH.


Development and application of high-performance liquid chromatography for the study of two new oxyprenylated anthraquinones produced by Rhamnus species.
Rhamnus spp. is known to contain biologically active anthraquinone secondary metabolites but the presence of oxyprenylated ones is not reported. To this aim, a new simple, and accurate analytical method was developed to reveal chemical fingerprint of these analytes in plant extracts. Plant samples were analysed after extraction with n-hexane (first step) and methanol (second step) using a C(18) column with a mobile phase composed of 35% of water:65% of methanol (both with 1% formic acid, v/v) at 0.7 mL min⁻¹ flow rate in gradient elution mode. For quantitative analyses, selective detection was performed at 435 nm. The limit of quantification (LOQ) was 0.5 μM, with the only exception of 3-geranyloxyemodin for which the LOQ value was 5.0 μM, and external matrix-matched standard curves showed linearity up to 125 μM. The within- and between-batch precision (RSD%) values ranged from 0.2% to 12.9% while within- and between-batch trueness (bias%) values ranged from 12.2% to 12.7%. The method was applied to evaluate for the first time the presence and the quantities of oxyprenylated anthraquinones in Rhamnus spp. barks as well as the anthraquinone profile of Rhamnus pumila Turra. The proposed method could be directly applied to the selective quantification of these analytes in natural sources.


Senescence marker protein-30 knockout mouse as a novel murine model of senile lung.
Senescence marker protein-30 (SMP30) was originally identified as a novel protein of which expression decreases in an androgen-independent manner with aging in the rat liver and functions to protect cells from apoptosis. By reverse transcription-polymerase chain reaction analysis, SMP30 mRNA transcripts were found in the mouse lung, liver, kidney, testis and cerebrum. We examined SMP30 expression in the mouse liver, kidney and lung during aging and a distinct temporal profile of SMP30 expression was found in each tissue; the SMP30 mRNA level peaked at 1-3 months of age and decreased thereafter in the liver (the highest at 1 month of age followed by a rapid decline and consistently low thereafter in the kidney), and peaked at 12 months of age in the lung. To investigate the physiological role of SMP30 in the lung, immunohistochemical studies of wild-type (SMP30Y/+) mice and histopathological examinations of SMP30 knockout (SMP30Y/-) mice were performed. Immunoreactivity against anti-SMP30 antibody was mainly detected in bronchial epithelial cells and strongly detected at 6-12 months of age. Morphometric analysis was performed to measure the mean linear intercept and destructive index, and found peripheral airspace enlargement without alveolar destruction in SMP30Y/- mice at 1, 3 and 6 months of age compared with the SMP30Y/+ mice. Our results strongly suggest that SMP30Y/- mice could be a novel model for a senile lung and further examinations of SMP30Y/- mice may offer clues to elucidate the mechanisms of the development of pulmonary diseases in the elderly.


False Identity: Lymphoid Hyperplasia Imitating a Large Paraganglioma.
The danger of the parapharyngeal space mass comes from the small space and vital neighboring structures. Its differential diagnosis is broad, however benign lymphoid hyperplasia in this region has not been previously reported. The clinical presentation, imaging, surgical findings and pathology slides were reviewed in an adult patient with a parapharyngeal space mass. The literature on somatostatin-positive parapharyngeal space lesions was reviewed. A 51-year old male with otalgia for 3 months, hearing loss, and tinnitus underwent audiogram, revealing asymmetric hearing loss. Laryngoscopy demonstrated a paretic true vocal cord. Subsequent MRI demonstrated 4.5 cm post-styloid parapharyngeal space mass displacing the carotid artery anterolaterally. Octreoscan scan showed significant uptake of the somatostatin analog. Angiogram showed prominent vascular blush. The mass was excised transcervically and histopathology demonstrated lymphoid hyperplasia. This case demonstrates that post-styloid parapharyngeal masses may be lateral retropharyngeal nodes. An octreotide-positive lymphoid hyperplasia has never been previously reported.


Patterns of use of vascular catheters for hemodialysis in children in the United States.
Arteriovenous fistulas (AVFs) and grafts (AVGs) have been associated with improved clinical outcomes in children and adults with end-stage renal disease (ESRD) on maintenance hemodialysis (HD) therapy, but use of vascular catheters is high. Identifying the reasons for the high prevalence of vascular catheters in children on HD therapy is necessary to assess whether targeted interventions may increase the prevalence of AVFs/AVGs. Retrospective cohort study. Children younger than 18 years on HD therapy in the 2001 to 2003 ESRD Clinical Performance Measures (CPM) Projects followed up in the US Renal Data System transplant files through December 31, 2004. Vascular access type and reasons for use of a vascular catheter. Demographic/clinical characteristics, including the reason provided for use of a vascular catheter, and the association of type of vascular access and (1) patient size and (2) time to kidney transplantation. Of 1,284 prevalent pediatric CPM patients examined, 529 (41%) had an AVF/AVG and 755 (59%) had a vascular catheter. Of 755 children with a catheter, "small body size" was a commonly listed reason (N = 142); 49% of these children weighed 20 kg or more. Of 53 patients with catheters described as having an "AVF/AVG maturing" and present in the consecutive ESRD CPM project year, 64% had a functioning AVF/AVG the following year. For those with "transplantation scheduled" listed as a reason for a vascular catheter (N = 83), 69% underwent transplantation within 1 year, and median time to transplantation was 115 days. Of all children with vascular catheters (N = 755), 32.2% underwent transplantation within 1 year, and median time to transplantation was 264 days compared with 21.7% and 347 days for those with AVFs/AVGs, respectively (N = 529). Of the 445 incident children in this cohort, 89% had a vascular catheter at dialysis therapy initiation. Because of study design, only associations can be described. Vascular catheter use in children on HD therapy is high. This is partially explained by expeditious transplantation and technical barriers to AVF/AVG placement in small children; however, only one-third of patients with a vascular catheter underwent transplantation within 1 year. Interventions to decrease vascular catheter use in this population may be necessary.


Infants' transition from milk to solid foods - the lived experiences of first-time parents.
Purpose: During the transition from ingesting milk to ingesting solid food, infants substantiate their eating habits. The present study focuses on this transition. Specifically, it aimed to explore first-time parents' lived experiences of their infants' transition from milk to solid foods.Method: The study is based on the descriptive phenomenological approach Reflective Lifeworld Research (RLR). Ten mothers and ten fathers were interviewed twice; when the infants were aged four to five months and again at seven to eight months of age. Data were analysed according to RLR principles.Results: The findings show that the transition from milk to solid food is a demanding in-between phase. The physically intimate feeding situation is replaced by unfamiliar situations in which parents and infant are physically separated and new types of food are introduced. The process of feeding requires parents' full attention and sensitivity towards the infant's reactions.Conclusion: The study highlights how shared parental experiences were reflected in frames for how a meal should normally proceed, including parents' desire to create healthy eating habits and uphold harmony duringfamily mealsWe suggest for health professionals to present parents with a wider frame of normality, especially as concerns the concept of what constitutes "normal" eating patterns.


How representative are the known structures of the proteins in a complete genome? A comprehensive structural census.
Determining how representative the known structures are of the proteins encoded by a complete genome is important for assessing to what extent our current picture of protein stability and folding is overly influenced by biases in the structure databank (PDB). It is also important for improving database-based methods of structure prediction and genome annotation. The known structures are compared to the proteins encoded by eight complete microbial genomes in terms of simple statistics such as sequence length, composition and secondary structure. The known structures are represented by a collection of nonhomologous domains from the PDB and a smaller list of 'biophysical proteins' on which folding experiments have concentrated. The proteins encoded by the genomes are considered as a whole and divided into various regions, such as known-structure homologue, low complexity (nonglobular), transmembrane or linker. Various tests are performed to assess the significance of the reported differences, in both a practical and a statistical sense. The proteins encoded by the genomes are significantly different from those in the PDB. Their sequence lengths, which follow an extreme value distribution, are longer than the PDB proteins and much longer than the biophysical proteins. Their composition differs from the PDB proteins in having more Lys, Ile, Asn and Gln and less Cys and Trp. This is true overall and especially for the regions corresponding to soluble proteins of as yet unknown fold. Secondary-structure prediction on these uncharacterized regions indicates that they contain on average more helical structure than the PDB; differences about this mean are small, with yeast having slightly more sheet structure and Haemophilus influenzae and Helicobacter pylori more helical structure. Further information is available through the GeneCensus system at http://bioinfo.mbb.yale.edu/genome.


Sensory experience regulates cortical inhibition by inducing IGF1 in VIP neurons.
Inhibitory neurons regulate the adaptation of neural circuits to sensory experience, but the molecular mechanisms by which experience controls the connectivity between different types of inhibitory neuron to regulate cortical plasticity are largely unknown. Here we show that exposure of dark-housed mice to light induces a gene program in cortical vasoactive intestinal peptide (VIP)-expressing neurons that is markedly distinct from that induced in excitatory neurons and other subtypes of inhibitory neuron. We identify Igf1 as one of several activity-regulated genes that are specific to VIP neurons, and demonstrate that IGF1 functions cell-autonomously in VIP neurons to increase inhibitory synaptic input onto these neurons. Our findings further suggest that in cortical VIP neurons, experience-dependent gene transcription regulates visual acuity by activating the expression of IGF1, thus promoting the inhibition of disinhibitory neurons and affecting inhibition onto cortical pyramidal neurons.


Comparison of Quality Metrics for Pediatric Shunt Surgery and Proposal of the Negative Shunt Revision Rate.
Shunt surgery is common in pediatric neurosurgery and is associated with relevant complication rates. We aimed to compare previously published metrics in a single data set and propose the Negative Shunt Revision Rate (NSRR), defined as proportion of shunt explorations revealing a properly working system, as a new quality metric. Retrospective analysis of our shunt surgery activity in 2015 was performed. Demographic, clinical, and radiologic variables were extracted from electronic medical notes. Surgical Activity Rate, Revision Quotient, 30-day shunt malfunction rate, 90-day global shunt revision rate, Preventable Shunt Revision Rate, and novel NSRR were calculated. Of 60 shunt operations analyzed, 18 (39%) were new shunt insertions, and 42 (70%) were revisions. Median age was 18 months (range, 0.03-204 months), and main etiologies were posthemorrhagic (n = 16; 41%), congenital (n = 11; 28%), and tumor-associated (n = 8; 21%) hydrocephalus. Within 90 days after index surgery, 13 shunt failures occurred, predominantly owing to proximal failure (n = 6; 46%). Surgical Activity Rate was 0.127, Revision Quotient was 2.333, 30-day shunt malfunction rate was 0.166, 90-day global shunt revision rate was 21.7%, and Preventable Shunt Revision Rate was 38.5%. NSRR was 7.1%. Our results correlate with published values and offer measurement of quality that can be compared across studies and considered patient-oriented, easily measurable, and potentially modifiable. We propose NSRR as a new quality metric, covering an aspect of shunt surgery that was not addressed previously.


circ_0038718 promotes colon cancer cell malignant progression via the miR-195-5p/Axin2 signaling axis and also effect Wnt/β-catenin signal pathway.
Colon cancer (CC) is one of the most common cancers whose progression is regulated by a number of factors, including circular RNAs (circRNAs). Nonetheless, circ_0038718 is a novel circRNA, and its regulatory mechanism in CC remains unclear. Real-time quantitative PCR (qRT-PCR) was performed to detect the expression of circ_0038718, miR-195-5p and Axin2. Western blot was conducted to determine the protein expression of Axin2 and the key proteins on Wnt/β-catenin signaling pathway. Oligo (dT) 18 primers and RNase R were employed to identify the circular features of circ_0038718, and the location of circ_0038718 in cells was detected via nucleocytoplasmic separation. Dual-luciferase reporter assay and RNA binding protein immunoprecipitation experiment were carried out to investigate the molecular mechanism of circ_0038718/miR-195-5p/Axin2. Additionally, MTT assay was conducted to assess cell proliferation; Transwell assay was performed to evaluate cell migration and invasion, respectively. The effect of circ_0038718 on CC tumor growth was tested through tumor formation in nude mice. circ_0038718 was highly expressed in CC and could sponge miR-195-5p in cytoplasm. Silencing circ_0038718 suppressed the proliferative, migratory and invasive abilities of CC cells, while the promoting effect of high circ_0038718 expression on CC cells was reversed upon miR-195-5p over-expression. Axin2 was a downstream target of miR-195-5p and could regulate the Wnt/β-catenin signaling pathway. Axin2 expression was modulated by circ_0038718/miR-195-5p. Knockdown of Axin2 could also attenuate the promoting effect of high circ_0038718 expression on CC cell malignant progression, thus inhibiting tumor growth. circ_0038718 is able to facilitate CC cell malignant progression via the miR-195-5p/Axin2 axis, which will provide a new idea for finding a novel targeted treatment of CC.


Novel genes associated with folic acid-mediated metabolism in mouse: A bioinformatics study.
Folic acid plays an essential role in the central nervous system and cancer. This study aimed to screen genes related to folic acid metabolism. Datasets (GSE80587, GSE65267 and GSE116299) correlated to folic acid were screened in the Gene Expression Omnibus. Weighed gene co-expression network analysis was performed to identify modules associated with sample traits of folic acid and organs (brain, prostate and kidney). Functional enrichment analysis was performed for the eigengenes in modules that were significantly correlated with sample traits. Accordingly, the hub genes and key nodes in the modules were identified using the protein interaction network. A total of 17,252 genes in three datasets were identified. One module, which included 97 genes that were highly correlated with sample traits (including folic acid treatment [cor = -0.57, P = 3e-04] and kidney [cor = -0.68, p = 4e-06]), was screened out. Hub genes, including tetratricopeptide repeat protein 38 (Ttc38) and miR-185, as well as those (including Sema3A, Insl3, Dll1, Msh4 and Snai1) associated with "neuropilin binding", "regulation of reproductive process" and "vitamin D metabolic process", were identified. Genes, including Ttc38, Sema3A, Insl3, Dll1, Msh4 and Snai1, were the novel factors that may be associated with the development of the kidneys and related to folic acid treatment.


Association of community level social trust and reciprocity with mortality: a retrospective cohort study.
Whether community level social capital is associated with mortality within an Asian population is yet unclear. The study population was derived from the Korean National Health Insurance Service-National Sample Cohort. A total of 636,055 participants were followed-up during 2012-2013 for deaths from all causes, cardiovascular disease (CVD), cancer, and other causes. Community level social trust and reciprocity at the administrative district level were derived from the Korean Community Health Survey. Cox proportional hazards regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for mortality according to levels of community level social trust and reciprocity. Compared to participants who reside in areas within the lower half of community level social trust, those who reside in areas within the upper half had lower risk of death from all causes (aHR 0.84, 95% CI 0.78-0.89), CVD (aHR 0.82, 95% CI 0.67-0.99), and cancer (aHR 0.85, 95% CI 0.73-0.98). Similarly, residing in areas in the upper half of community level social reciprocity was associated with reduced risk for all-cause mortality (aHR 0.80, 95% CI 0.75-0.86). The protective association of high community level social trust and reciprocity on mortality remained after additional adjustments for smoking, alcohol intake, and physical activity. Residing in areas with high community level social trust and reciprocity may be associated with better population health status.