Garcinia cambogia, Either Alone or in Combination With Green Tea, Causes Moderate to Severe Liver Injury.
Garcinia cambogia, either alone or with green tea, is commonly promoted for weight loss. Sporadic cases of liver failure from G cambogia have been reported, but its role in liver injury is controversial. Among 1418 patients enrolled in the Drug-Induced Liver Injury Network (DILIN) from 2004 to 2018, we identified 22 cases (adjudicated with high confidence) of liver injury from G cambogia either alone (n = 5) or in combination with green tea (n = 16) or Ashwagandha (n = 1). Control groups consisted of 57 patients with liver injury from herbal and dietary supplements (HDS) containing green tea without G cambogia and 103 patients from other HDS. Patients who took G cambogia were between 17 and 54 years, with liver injury arising 13-223 days (median = 51) after the start. One patient died, one required liver transplantation, and 91% were hospitalized. The liver injury was hepatocellular with jaundice. Although the peak values of aminotransferases were significantly higher (2001 ± 1386 U/L) in G cambogia group (P < .018), the median time for improvement in total bilirubin was significantly lower compared with the control groups (10 vs 17 and 13 days; P = .03). The presence of HLA-B∗35:01 allele was significantly higher in the G cambogia containing HDS (55%) compared with patients because of other HDS (19%) (P = .002) and those with acute liver injury from conventional drugs (12%) (P = 2.55 × 10-6). The liver injury caused by G cambogia and green tea is clinically indistinguishable. The possible association with HLA-B∗35:01 allele suggests an immune-mediated mechanism of injury. gov number: NCT00345930.


Total synthesis of fellutamide B and deoxy-fellutamides B, C, and D.
The total syntheses of the marine-derived lipopeptide natural product fellutamide B and deoxy-fellutamides B, C, and D are reported. These compounds were accessed through a novel solid-phase synthetic strategy using Weinreb amide-derived resin. As part of the synthesis, a new enantioselective route to (3R)-hydroxy lauric acid was developed utilizing a Brown allylation reaction followed by an oxidative cleavage-oxidation sequence as the key steps. The activity of these natural products, and natural product analogues was also assessed against Mycobacterium tuberculosis in vitro.


The effects of Thalamic Deep Brain Stimulation on speech dynamics in patients with Essential Tremor: An articulographic study.
Acoustic studies have revealed that patients with Essential Tremor treated with thalamic Deep Brain Stimulation (DBS) may suffer from speech deterioration in terms of imprecise oral articulation and reduced voicing control. Based on the acoustic signal one cannot infer, however, whether this deterioration is due to a general slowing down of the speech motor system (e.g., a target undershoot of a desired articulatory goal resulting from being too slow) or disturbed coordination (e.g., a target undershoot caused by problems with the relative phasing of articulatory movements). To elucidate this issue further, we here investigated both acoustics and articulatory patterns of the labial and lingual system using Electromagnetic Articulography (EMA) in twelve Essential Tremor patients treated with thalamic DBS and twelve age- and sex-matched controls. By comparing patients with activated (DBS-ON) and inactivated stimulation (DBS-OFF) with control speakers, we show that critical changes in speech dynamics occur on two levels: With inactivated stimulation (DBS-OFF), patients showed coordination problems of the labial and lingual system in terms of articulatory imprecision and slowness. These effects of articulatory discoordination worsened under activated stimulation, accompanied by an additional overall slowing down of the speech motor system. This leads to a poor performance of syllables on the acoustic surface, reflecting an aggravation either of pre-existing cerebellar deficits and/or the affection of the upper motor fibers of the internal capsule.


Risk factors of recurrence and complication in radiofrequency catheter ablation of atrioventricular reentrant tachycardia in children and adolescents.
To compare potential risk factors for complications and recurrence after radiofrequency catheter ablation in symptomatic atrioventricular reentrant tachycardia in children and adolescents. We retrospectively reviewed the data of 213 consecutive patients with symptomatic atrioventricular reentrant tachycardia who underwent both electrophysiological study and radiofrequency catheter ablation, divided these patients into two groups, children (age < 12 years) and adolescents (12 < or = rage, 18 years), and compared the location of the accessory pathway, success rate, recurrence rate, complications, presence of congenital heart disease, presence of intermittent ventricular pre-excitation, and presence of Wolff–Parkinson–White syndrome in the two groups. The position of the accessory pathway was mostly right sided in children (61.3%) and left sided in adolescents (61.5%). Children had significantly more congenital heart disease than adolescents (6.4% versus 0.8%). Univariate analysis showed children or adolescents with right-sided accessory pathways to be 6.84 times and those with accessory pathways on both sides of the septum 25 times more likely to relapse than those with a single accessory pathway. Multivariate analysis indicated that children or adolescents with two accessory pathways were six times, and those with intermittent ventricular pre-excitation nine times more at risk of relapsing following radiofrequency ablation than those with single accessory pathways. All five complications occurred in children. The findings suggest that the position and number of accessory pathways and presence of intermittent ventricular pre-excitation are related to risks of recurrence of atrioventricular reentrant tachycardia in children and adolescents.


[Antimicrobial action of the combined preparation sulfamoxole/trimethoprim in vitro (author's transl)].
A number of different methods were used to test the in vitro antimicrobial activity of the combination of N1-(4,5-dimethyl-2-oxazolyl)-sulfanilamide (sulfamoxole) and 2,4-diamino-5-(3,4,5-trimethoxy-benzyl)-pyrimidine (trimethoprim). 1. The minimum bacteriostatic inhibitory concentratiions of the sulfamoxole/trimethoprim combination (5 + 1) (CN 3123; Nevin; Supristol) were determined for 131 gram-positive and gram-negative strains of bacteria. More than 88% of the strains tested were found to be highly sensitive to the combination (M1C 0.1-3.75 mug/ml). 2. Comparative studies with the combinations sulfamoxole/trimethoprim and sulfamethoxazole/trimethoprim revealed no relevant differences of the M1C-values. 3. The synergistic effects of sulfamoxole and trimethoprim can be demonstrated with the aid of the agar dilution and agar diffusion tests using various types of bacteria and different ratios of sulfamoxole and trimethoprim. 4. Results obtained by studies on growth kinetics also demonstrate the synergistic and potentiating effect of combining sulfamoxole with trimethoprim and bactericidal properties are achieved.


Preclinical trial of the effectiveness of a safety nasogastric tube to detect the tube position based on tidal volume and pepsin assay results in the gastrointestinal tract of Macaca fascicularis.
Tube misplacement into the tracheobronchial tract is associated with pneumothorax in 0.5% of cases. NGT verification only detects the position of the tube at the end of the procedure. Therefore, a safe nasogastric tube (SNGT) was created to detect the NGT position in real time in a simple and inexpensive way. This study aimed to prove the effectiveness of the SNGT prototype in Macaca fascicularis. An SNGT producing 50% of the TV had 100% sensitivity and specificity in detecting the position of the tube at 100% of the TV, with a sensitivity of 100% and a specificity of 87.5%. There was a significant difference between the movement of the SNGT 50% TV and SNGT 100% TV airbags (p ≤ 0.05). However, there was no significant difference between the accuracy of placement of the 50% TV SNGT, 100% TV SNGT, and conventional NGT (p > 0.05). The pepsin enzyme had better sensitivity (100%) than pH paper (91.66%) in detecting the end-of-procedure tube position. This research has the potential to advance into human clinical trials. SNGTs are highly effective in detecting the NGT position inside the respiratory and digestive tracts to prevent misplacement.


Necrotizing Fasciitis and The Diabetic Foot.
Necrotizing fasciitis (NF) represents a rapidly progressive, life-threatening infection involving skin, soft tissue, and deep fascia. An early diagnosis is crucial to treat NF effectively. The disease is generally due to an external trauma that occurs in predisposed patients: the most important risk factor is represented by diabetes mellitus. NF is classified into 3 different subtypes according to bacterial strains responsible: type 1 associated to polymicrobial infection, type 2 NF, generally associated to Streptococcus species, often associated to Staphylococcus aureus and, eventually, Type 3, due to Gram-negative strains, such as Clostridium difficile or Vibrio. NF is usually characterized by the presence of the classic triad of symptoms: local pain, swelling, and erythema. In daily clinical practice immune-compromised or neuropathic diabetic patients present with atypical symptomatology. This explains the high percentage of misdiagnosed cases in the emergency department and, consequently, the worse outcome presented by these patients. Prompt aggressive surgical debridement and antibiotic systemic therapy are the cornerstone of its treatment. These must be associated with an accurate systemic management, consisting in nutritional support, glycemic compensation, and hemodynamic stabilization. Innovative methods, such as negative pressure therapy, once the acute conditions have resolved, can help fasten the surgical wound closure. Prompt management can improve prognosis of patients affected from NF reducing limb loss and saving lives.


Electric cataract: a rare clinical entity.
Bilateral crystalline lens opacities developed in a 39-year-old black male who had been involved in an electrical accident approximately 1 yr before our examination. The anterior subcapsular opacities had feathered edges and a slightly raised center. The typical appearance and progressive course of the opacities, as well as the history, led to the diagnosis of electric cataract.


In vitro antibacterial activity of S-4661, a new parenteral carbapenem, against urological pathogens isolated from patients with complicated urinary tract infections.
The antibacterial activity of S-4661, a new parenteral carbapenem antibiotic, was assessed against the major urological pathogens isolated from patients with complicated urinary tract infections. S-4661 was slightly less active than imipenem and panipenem, but more active than meropenem and ceftazidime against Gram-positive bacteria. Against Gram-negative bacteria, S-4661 was similar to meropenem, similar to or more effective than imipenem, and more active than panipenem and ceftazidime. Thus S-4661 possesses potent and well-balanced wide-spectrum antibacterial activity against various urological pathogens.


Inhibitory effects of loading with the calcium-chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) on amylase release and cellular ATP level in rat parotid cells.
Rat parotid cells were loaded with the Ca2(+)-chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), by incubation with the acetoxymethyl ester of BAPTA (BAPTA-AM). The BAPTA loading inhibited amylase release induced by beta-adrenergic receptor stimulation without affecting the basal release, and the IC50 value was 25 microM. Incubation of cells with BAPTA-AM also suppressed cellular ATP levels considerably. At 100 microM BAPTA-AM, the ATP level fell to about 50% of the control. A decrease in ATP levels by incubation with oligomycin, a mitochondrial inhibitor, correlated well with the inhibition of amylase release. Although these results do not exclude the possibility that cytosolic free Ca2+ is involved in the regulation of cyclic AMP-mediated amylase release, they suggest that the amylase release inhibition with BAPTA loading may be due, in part, to a decrease in cellular ATP levels. Therefore, the exact mode of the BAPTA action must be interpreted with caution.


Alignment and assembly of adsorbed collagen molecules induced by anisotropic chemical nanopatterns.
Collagen, a protein widely used to control cell-material interactions, is known to self-assemble in solution. Supramolecular structures also form on material surfaces following collagen adsorption. Herein, we report the use of anisotropic, flat, surface chemical nanopatterns, which consist of alkyl-terminated tracks drawn in an oligo(ethylene glycol)-terminated matrix, to direct collagen adsorption. As revealed by atomic force microscopy, the spontaneous collagen adsorption performed on such patterned substrates results in the accumulation of collagen on the hydrophobic tracks. Moreover, the width of the tracks (30-90 nm), which is much smaller than the length of the collagen molecule (approximately 300 nm), is the origin of preferential alignment of the molecules and of their assembly into continuous bundles of adsorbed collagen. This chemical guidance effect due to self-confinement of proteins upon adsorption may bring novel and valuable applications, specifically in biomaterials science and cell growth control.


The Plasticity of Th17 Cells in the Pathogenesis of Rheumatoid Arthritis.
Helper T (Th) cells play an important role in the pathogenesis of autoimmune diseases, including rheumatoid arthritis (RA). It has been revealed that Th17 cells can shift to Th1 cells (i.e., "nonclassic Th1 cells"), which are reported to be more pathogenic than Th17 cells per se. Thus, the association of Th cells in the pathogenesis of autoimmune disease has become more complicated. We recently reported using peripheral blood from untreated and early-onset RA patients that the ratio of CD161+Th1 cells (i.e., Th17-derived Th1 cells to CD161+Th17 cells) is elevated and that levels of interferon-γ (IFNγ)+Th17 cells are inversely correlated with levels of anti-CCP antibodies. Here, we review the plasticity of Th17 cells in the pathogenesis of RA, suggesting possible implications for novel therapies.


The impact of neuroimmune changes on development of amyloid pathology; relevance to Alzheimer's disease.
Neuroinflammatory changes are a characteristic of several, if not all, neurodegenerative diseases including Alzheimer's disease and are typified by increased microglial activation. Microglia express several receptors making them highly reactive and plastic cells, and, at least in vitro, they adopt different phenotypes in a manner analogous to their peripheral counterparts, macrophages. Microglia also express numerous cell surface proteins enabling them to interact with cells and the evidence indicates that maintenance of microglia in a quiescent state relies, at least to some extent, on an interaction with neurons by means of specific ligand-receptor pairs, for example CD200-CD200R. It is clear that microglia also interact with T cells and recent evidence indicates that co-incubation of microglia with T helper type 1 cells markedly increases their activation. Under normal conditions, small numbers of activated T cells gain entry to the brain and are involved in immune surveillance but infiltration of significant numbers of T cells occurs in disease and following injury. The consequences of T cell infiltration appear to depend on the conditions, with descriptions of both neurodestructive and neuroprotective effects in animal models of different diseases. This review will discuss the modulatory effect of T cells on microglia and the impact of infiltration of T cells into the brain with a focus on Alzheimer's disease, and will propose that infiltration of interferon-γ-producing cells may be an important factor in triggering inflammation that is pathogenic and destructive.


A rapid membrane based immunobinding assay for the detection of dengue virus in tissue culture.
A rapid, simple dot immunoassay (DOTIA) was developed and evaluated for the detection of dengue-1 viral antigen in infected Aedes albopictus C6/36 cells. Dengue virus infected cells were solubilize in sodium dodecyl sulfate (SDS) and the lysate was pressure filtered through a hydrophobic polyvinylidene difluoride (PVDF) membrane. Viral antigen retained in the membrane was detected by a dengue-1 type specific monoclonal antibody and a peroxidase-labeled second antibody. Addition of tetramethylbenzidene (TMB) substrate produced a blue-colored precipitate which allowed for quantitation of viral antigen using a portable white light reflectance densitometer. Estimate of viral infectivity in the cell lysates tested by the DOTIA was determined by standard plaque assays and the results indicated an excellent correlation between these two methods. The dot immunoassay detected dengue viral antigen in infected C6/36 cells between days three and eight post-inoculation, depending on the titer of the inoculum. An infectivity titer of at least 10(3) plaque forming units (PFU) per ml was required to detect antigen by the DOTIA. The DOTIA also detected viral antigen in cells inoculated with twelve acute sera from known dengue-1 virus infected patients, thus demonstrating that this technique is useful for the detection and identification of dengue-1 virus from clinical specimens.


Pethidine binding in plasma: effects of methodological variables.
Several methodological variables potentially influencing the plasma protein binding of [14C]-pethidine in vitro were investigated using equilibrium dialysis and rigorous pH control. Ionic strength of buffer, pethidine concentration and 21 days of plasma samples frozen to -8 degrees C did not affect the outcome of the binding experiments. Unbound fraction decreased with increasing temperatures between 25 degrees C and 37 degrees C. Unbound fraction decreased with increased pH between pH 7.0 and 8.0; the mean unbound fraction at an equilibrium pH of 7.4 and at 37 degrees C was 0.58 (s.d. 0.03, n = 58). It is likely that previous reports of pethidine unbound fraction as being between 0.2 and 0.4 represent artefacts caused by inadequate pH control during dialysis.


Study on the Pakistan stock market using a new stock crisis prediction method.
A Stock market collapse occurs when stock prices drop by more than 10% across all main indexes. Predicting a stock market crisis is difficult because of the increased volatility in the stock market. Stock price drops can be triggered by a variety of factors, including corporate results, geopolitical tensions, financial crises, and pandemic events. For scholars and investors, predicting a crisis is a difficult endeavor. We developed a model for the prediction of stock crisis using Hybridized Feature Selection (HFS) approach. Firstly, we went for the suggestion of the HFS method for the removal of stock's unnecessary financial attributes. The Naïve Bayes approach, on the other hand, is used for the classification of strong fundamental stocks. In the third step, Stochastic Relative Strength Index (StochRSI) is employed to identify a stock price bubble. In the fourth step, we identified the stock market crisis point in stock prices through moving average statistics. The fifth is the prediction of stock crises by using deep learning algorithms such as Gated Recurrent Unit (GRU) and Long-Short Term Memory (LSTM). Root Mean Square Error (RMSE), Mean Squared Error (MSE) and Mean Absolute Error (MAE) are implemented for assessing the performance of the models. The HFS-based GRU technique outperformed the HFS-based LSTM method to anticipate the stock crisis. To complete the task, the experiments used Pakistan datasets. The researchers can look at additional technical factors to forecast when a crisis would occur in the future. With a new optimizer, the GRU approach may be improved and fine-tuned even more.


Clinical evaluation of a new device in the assessment of peripheral sensory neuropathy in diabetes.
Current National Institute for Health and Clinical Excellence guidelines state that patients with diabetes should have annual examination of their feet to exclude signs of sensory impairment. The VibraTip is a new disposable device producing a vibratory stimulus, which has been developed in order to screen for peripheral sensory neuropathy in diabetes. This study was designed to evaluate the device by assessing intra-rater reliability and comparing the ability of the VibraTip to detect or exclude peripheral sensory neuropathy with other bedside methods. One hundred and forty-one patients with diabetes (Type 1 or Type 2) were examined for diabetic peripheral sensory neuropathy using a Neurothesiometer, 10-g monofilament, a 128-Hz tuning fork, a Neurotip™ and a VibraTip. The failure to perceive the Neurosthesiometer stimulus at ≥ 25 V in either foot was considered the reference method for the presence of peripheral sensory neuropathy. Receiver operating characteristic curves were produced for each device and the sensitivity, specificity, predictive values and likelihood ratios for the diagnosis of peripheral sensory neuropathy were calculated. Repeat testing with the VibraTip was performed in 18 patients and intra-rater reliability assessed using Cronbach alpha. Analysis of the area under the receiver operating characteristic curves showed that the 10-g monofilament was significantly better than the 128-Hz tuning fork (P = 0.0056) and the Neurotip (P = 0.0022), but was no different from the VibraTip (P = 0.3214). The alpha coefficient for the VibraTip was calculated to be 0.882, indicating good reliability. The VibraTip is a device comparable with the 10-g monofilament and therefore could be considered a useful tool for screening for peripheral sensory neuropathy in diabetes.


False moves for survival: error-prone DNA repair in adaptive immunity.
Genetic stability and flexibility are major determinants of organismic integrity and evolution, respectively. An intricate DNA repair network protects the genome from multiple environmental challenges, but complex specialized processes may also allow enhanced mutability in critical situations. The interdependence and interference of these two systems is best exemplified in the adaptive immune system. Here, the coordinated reprogramming of DNA processing pathways allows the adaptation of the antibody response to specific infections, but in parallel increases the risk of malignant transformation of the affected B cells. The respective decisions in DNA repair pathway choice have now been linked to damage bypass processes occurring at stalled replication forks. Future research in this area may shed light on fundamental questions of both immunology and genetics, and provide translational concepts for improved cancer prognosis and therapy.


Rapid activation of haemostasis after hormonal emergency contraception.
Hormonal emergency contraception (EC) is a well established contraceptive method, recommended to all women, although the effects on haemostais are not fully evaluated. The aim of this study was to evaluate whether exposure to EC has effects on well established cardiovascular risk factors, and also to examine whether differences exist between two EC treatments. In a prospective randomized cross over design 11 women used two different EC methods, one with estrogen and levonorgestrel (EE-EC) and one with levonorgestrel only (LNG-EC). Plasma concentrations of haemostatic factors (APC resistance, antithrombin, fibrinogen, prothrombin fragment 1 + 2, free protein S, factorVII and PAI-1), sex-hormone-binding globulin (SHBG), the apolipoprotein (apo)B/apoA1 ratio and C-reactive protein (CRP) were followed frequently during the following 48 hours. A rapid haemostatic activation was induced with both treatments, although more pronounced with EE-EC. Already two hours after EC, the plasma concentrations of haemostatic parameters and SHBG were significantly different from baseline concentrations. An ETP-based APC-resistance method showed increased APC resistance with EE-EC and decreased APC resistance with LNG-EC. The ApoB/ApoA1 ratio was affected in a favourable direction with EE-EC.CRP increased slightly regardless of treatment. Even a very short exposure to exogenous sex hormones causes prompt effects on hepatic protein synthesis and the coagulation system. This must be taken into consideration whenever exogenous steroid hormones are administered, especially to individuals with a genetic predisposition to thrombosis or transiently disturbed haemostasis.


Cardiovascular disease markers in type 2 diabetes: the effects of a moderate home-based exercise training programme.
Patients with T2DM have an increased risk of CVD. Prevention of CVD represents the major goal of all treatment of T2DM, and early intervention in those patients at particularly high risk is important.We measured the insulin sensitivity and plasma biomarkers of CVD to determine whether a home-based exercise training program improves biomarker levels and insulin sensitivity. Patients with T2DM (n=12), IGT (n=4) and healthy control subjects (n=9) were studied before and after eight weeks of exercise training by rowing ergometry at 65-70% of peak oxygen uptake. 1) patients with T2DM have elevated plasma concentrations of CVD biomarkers compared to the matched control and IGT groups; 2) a moderate to vigorous intensity home-based training program did not reduce plasma concentrations of these CVD markers; 3) insulin sensitivity improved as a result of exercise training in the control group, but not in the T2DM group.


POTEE stimulates the proliferation of pancreatic cancer by activating the PI3K/Akt/GSK-3β/β-catenin signaling.
To explore the role of POTEE in the malignant development of pancreatic cancer and the possible mechanism. POTEE levels in pancreatic cancer samples were detected. The relationship between POTEE level and clinical data of pancreatic cancer patients was analyzed. After knockdown of POTEE or treatment of the GSK-3β inhibitor, proliferative change in pancreatic cancer cells was assessed. Protein levels of vital genes in the PI3K/Akt/GSK-3β/β-catenin signaling influenced by POTEE were examined. POTEE was upregulated in pancreatic cancer samples. High level of POTEE indicated advanced tumor staging, large tumor size, and poor prognosis in pancreatic cancer patients. Knockdown of POTEE or treatment of Tideglusib remarkably attenuated proliferative ability in pancreatic cancer cells. Vital genes in the PI3K/Akt/GSK-3β/β-catenin signaling were downregulated by knockdown of POTEE. POTEE stimulates the proliferative ability in pancreatic cancer by activating the PI3K/Akt/GSK-3β/β-catenin signaling. High level of POTEE indicates advanced tumor staging, large tumor size and poor prognosis in pancreatic cancer patients.


MicroRNA-24-3p regulates Hodgkin's lymphoma cell proliferation, migration and invasion by targeting DEDD.
Hodgkin's lymphoma (HL) is a common hematologic tumor, and the incidence is increasing. At present, it is considered that miRNAs are closely related to HL. Substantial attention has been paid to the effects of miRNA on the pathophysiological process of HL. This study was focused on the potential role of miR-24-3p in HL by targeting DEDD. The reverse transcription-quantitative PCR (RT-qPCR) results demonstrated that miR-24-3p expression was highly elevated and DEDD expression reduced inversely in HL tissues compared to adjacent tissues. According to the results of CKK-8 assays, miR-24-3p was able to accelerate HL cell proliferation. In addition, the results of the Transwell assays also indicated that miR-24-3p promoted the invasion and migration abilities of HL cells. Moreover, the results demonstrated that miR-24-3p inhibited DEDD expression. Hence, the present study revealed that miR-24-3p could accelerate HL development through inhibiting DEDD.


Evaluation of a simple activity measurement method in rats.
[Purpose] Behavioral analysis is widely used in animal research. However, such analysis requires specialized equipment and can be difficult to perform. Therefore, this study aimed to explore and validate a simple behavioral analysis method. [Participants and Methods] For behavioral assessments, Wistar rats were placed in a rearing cage and videotaped from two directions: overhead and side view. The filmed videos were analyzed using ImageJ software to calculate the distance traveled and activity and inactivity times of the rats. Intraclass correlation coefficients 1 and 2 were calculated to examine the reliability of the behavioral analysis method. [Results] Intraclass correlation coefficients 1 and 2 for distance traveled and activity and inactivity times determined using the behavioral analysis method showed high reliability. [Conclusion] The behavioral analysis method validated in this study used inexpensive and easily accessible equipment and devices. The results show high correlation coefficients for the measurement of distance traveled and activity time performed by experimental animals, demonstrating the reliability of this simple method.


Engineered ketocarotenoid biosynthesis in the polyextremophilic red microalga Cyanidioschyzon merolae 10D.
The polyextremophilic Cyanidiophyceae are eukaryotic red microalgae with promising biotechnological properties arising from their low pH and elevated temperature requirements which can minimize culture contamination at scale. Cyanidioschyzon merolae 10D is a cell wall deficient species with a fully sequenced genome that is amenable to nuclear transgene integration by targeted homologous recombination. C. merolae maintains a minimal carotenoid profile and here, we sought to determine its capacity for ketocarotenoid accumulation mediated by heterologous expression of a green algal β-carotene ketolase (BKT) and hydroxylase (CHYB). To achieve this, a synthetic transgene expression cassette system was built to integrate and express Chlamydomonas reinhardtii (Cr) sourced enzymes by fusing native C. merolae transcription, translation and chloroplast targeting signals to codon-optimized coding sequences. Chloramphenicol resistance was used to select for the integration of synthetic linear DNAs into a neutral site within the host genome. CrBKT expression caused accumulation of canthaxanthin and adonirubin as major carotenoids while co-expression of CrBKT with CrCHYB generated astaxanthin as the major carotenoid in C. merolae. Unlike green algae and plants, ketocarotenoid accumulation in C. merolae did not reduce total carotenoid contents, but chlorophyll a reduction was observed. Light intensity affected global ratios of all pigments but not individual pigment compositions and phycocyanin contents were not markedly different between parental strain and transformants. Continuous illumination was found to encourage biomass accumulation and all strains could be cultivated in simulated summer conditions from two different extreme desert environments. Our findings present the first example of carotenoid metabolic engineering in a red eukaryotic microalga and open the possibility for use of C. merolae 10D for simultaneous production of phycocyanin and ketocarotenoid pigments.


Chyloperitoneum after blunt abdominal injury.
The objective of this study was to evaluate incidence of chylous injury in blunt trauma using a retrospective chart review. We present two patients who sustained chyle duct injury after blunt trauma. The first patient is a pedestrian struck by car. Abdominal CT scan revealed duodenal thickening and a moderate amount of paraduodenal fluid, which prompted surgical exploration. At laparotomy, the patient was found to have a disruption of his lymphatics at the level of the inferior vena cava (IVC) without duodenal injury treated with hemoclips, fibrin sealant and elemental gastrojejunal feeds. The second patient was involved in a high speed motor vehicle collision (MVC) resulting in transection of the mesentery of the transverse colon. Disrupted lacteals were treated intra-operatively with hemoclips and fibrin sealant decreasing the lymph leak. In both cases, the leak completely resolved with use of tube feedings with medium chain triglycerides. On literature review, six prior patients with spontaneous chylous retroperitoneum were described undergoing similar operative management. Chylous leakage due to blunt trauma is a rare finding. Mechanism of injury includes hyperextension or flexion resulting in stretching and shearing of the tethered lymphatics. Open ligation or clipping of the injured ducts seems effective. Tube feeds with medium chain triglycerides may enhance efficacy of operative treatment.


Complement and the prothrombotic state.
In 2007 and 2009, the regulatory approval of the first-in-class complement inhibitor eculizumab revolutionized the clinical management of 2 rare, life-threatening clinical conditions: paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). Although being completely distinct diseases affecting blood cells and the glomerulus, PNH and aHUS remarkably share several features in their etiology and clinical presentation. An imbalance between complement activation and regulation at host surfaces underlies both diseases precipitating in severe thrombotic events that are largely resistant to anticoagulant and/or antiplatelet therapies. Inhibition of the common terminal complement pathway by eculizumab prevents the frequently occurring thrombotic events responsible for the high mortality and morbidity observed in patients not treated with anticomplement therapy. Although many in vitro and ex vivo studies elaborate numerous different molecular interactions between complement activation products and hemostasis, this review focuses on the clinical evidence that links these 2 fields in humans. Several noninfectious conditions with known complement involvement are scrutinized for common patterns concerning a prothrombotic statues and the occurrence of certain complement activation levels. Next to PNH and aHUS, germline-encoded CD59 or CD55 deficiency (the latter causing the disease complement hyperactivation, angiopathic thrombosis, and protein-losing enteropathy), autoimmune hemolytic anemia, (catastrophic) antiphospholipid syndrome, and C3 glomerulopathy are considered. Parallels and distinct features among these conditions are discussed against the background of thrombosis, complement activation, and potential complement diagnostic and therapeutic avenues.


Human and machine: Evaluating whether action automation influences visual perception.
The action-specific account of perception suggests that our perceptual system is influenced by information about our ability to act in our environment and, thus, affects our perception. However, the specific information about action that is influential for perception is still largely unknown. For example, if a goal is achieved through automation rather than action, is perception influenced because the goal was achieved or is perception immune because the act was automated rather than performed by the observer? In four experiments, we examined whether automating a paddle to block a moving ball in a computer game similar to Pong affects perception of the ball's speed. Results indicate that the automation used here did not affect speed perception of the target. Whereas tools such as reach-extending sticks and various-sized paddles are both incorporated into one's body schema and also influence spatial perception, automation, our results imply that automation is not incorporated into one's body schema and does not affect spatial perception. The dissociation in how the mind treats tools versus automation could have several implications as automation becomes more prevalent in daily life.


Interprofessional education in Erlangen: A needs analysis and the conceptual work of a student working group.
Interprofessional education (IPE) is receiving growing significance both nationally and internationally. Despite this, organizational and curricular changes are posing challenges. The level of need for IPE and how changes can be made to curricula and infrastructure were investigated at the University of Erlangen in Germany. The student working group for interprofessional teaching (AGIL) has turned its attention to these issues. This group is composed of students from medicine, dentistry, molecular medicine, medical technology and speech therapy. In June, 2015, a needs analysis was carried out among the students in the study programs represented in the working group to assess the actual and target situation concerning IPE (n=1,105). In the search for answers and to better measure any needs, contact was sought with instructors. The majority of students feel that they are insufficiently educated in terms of interprofessional skills. A large proportion of the students wish to see expansion of the IPE offerings. Students also expressed a desire for additional spaces and welcomed the idea of an interprofessional learning center. AGIL began establishing interprofessional electives in October 2015. A concept for an interprofessional learning center was developed. Based on the survey results, a need for improvements to curricula and infrastructure can be seen; however, the results are limited to the student point of view. AGIL would like to establish more interprofessional electives. These courses would then facilitate curricular implementation. Modern ideas about study environments could be applied to IPE, in particular to promote informal forms of learning. Contact with instructors was crucial for the project work and should be expanded. Realizing and financing the learning center in Erlangen are now the future goals of AGIL. The aim is to create a foundation for this purpose.


The relationship between basal and luminal cytokeratins with histopathologic characteristics of canine mammary gland cancer.
Neoplasia occurs mostly in mammary glands in female dogs and mammary gland cancer is one of the causes of death in these animals cytokeratins are one of the most important of tumor markers for identification of tumor prognosis. In this study, 120 canine malignant tumor samples of mammary glands were studied. From each sample, a section was taken for hematoxylin-eosin staining and two sections for immunohistochemical staining of markers CK5/6 and CK7. Histopathology slides was evaluated by light microscope. The results show that the presence of markers CK7 and CK5/6 had no significant relationship with tumor grade and type (p<0.05). However, it seems that unlike humans, CK5/6 and CK7 is not an independent prognostic factor in canine mammary gland tumors.


Reforming Nitrate Metabolism for Enhancing L-Arginine Production in Corynebacterium crenatum Under Oxygen Limitation.
Various amino acids are widely manufactured using engineered bacteria. It is crucial to keep the dissolved oxygen at a certain level during fermentation, but accompanied by many disadvantages, such as high energy consumption, reactive oxygen species, and risk of phage infections. Thus, anaerobic production of amino acids is worth attempting. Nitrate respiration systems use nitrate as an electron acceptor under anoxic conditions, which is different from the metabolism of fermentation and can produce energy efficiently. Herein, we engineered Corynebacterium crenatum to enhance L-arginine production under anaerobic conditions through strengthening nitrate respiration and reforming nitrogen flux. The construction of mutant strain produced up to 3.84 g/L L-arginine under oxygen limitation with nitrate, and this value was 131.33% higher than that produced by the control strain under limited concentrations of oxygen without nitrate. Results could provide fundamental information for improving L-arginine production by metabolic engineering of C. crenatum under oxygen limitation.


Identification of long-range regulatory elements in the protocadherin-alpha gene cluster.
The clustered protocadherins (Pcdh) are encoded by three closely linked gene clusters (Pcdh-alpha, -beta, and -gamma) that span nearly 1 million base pairs of DNA. The Pcdh-alpha gene cluster encodes a family of 14 distinct cadherin-like cell surface proteins that are expressed in neurons and are present at synaptic junctions. Individual Pcdh-alpha mRNAs are assembled from one of 14 "variable" (V) exons and three "constant" exons in a process that involves both differential promoter activation and alternative pre-mRNA splicing. In individual neurons, only one (and rarely two) of the Pcdh alpha1-12 promoters is independently and randomly activated on each chromosome. Thus, in most cells, this unusual form of monoallelic expression leads to the expression of two different Pcdh-alpha 1-12 V exons, one from each chromosome. The two remaining V exons in the cluster (Pcdh-alphaC1 and alphaC2) are expressed biallelically in every neuron. The mechanisms that underlie promoter choice and monoallelic expression in the Pcdh-alpha gene cluster are not understood. Here we report the identification of two long-range cis-regulatory elements in the Pcdh-alpha gene cluster, HS5-1 and HS7. We show that HS5-1 is required for maximal levels of expression from the Pcdh alpha1-12 and alphaC1 promoters, but not the Pcdh-alphaC2 promoter. The nearly cluster-wide requirement of the HS5-1 element is consistent with the possibility that the monoallelic expression of Pcdh-alpha V exons is a consequence of competition between individual V exon promoters for the two regulatory elements.


Biomechanical properties of porcine flexor tendon fixation with varying throws and stitch methods.
The well-known suture technique configurations used for hamstring tendon autograft preparation in anterior cruciate ligament (ACL) reconstruction are the Krackow locking stitch and nonlocking stitch, such as a baseball stitch and a whipstitch. However, there are few data in the literature regarding biomechanical comparisons of suture techniques. The purpose of this study was to determine the properties of several current techniques of tendon graft suture employed in ACL reconstruction. Controlled laboratory study. Forty-two fresh-frozen porcine flexor digitorum tendons were used. Three stitch configurations (Krackow stitch [group K], baseball stitch [group B], and whipstitch [group W]) were assessed with varying suture throws (6 throws, group×6; 10 throws, group×10) using No. 5 Ethibond sutures. Each group was tested at 1500 loading cycles between 50 and 200 N. After loading cycles, the surviving tendons underwent a load-to-failure test. During the loading cycles, 3 of 7 specimens in group B×6 and all specimens in group W×6 failed by suture pullout. Four of 7 specimens in group B×10 and all specimens in group W×10 showed partial tearing of the tendon. Elongation of group B×10 and group W×10 showed significantly greater elongation than other groups (P < .05). Maximum loads at failure showed significant differences between group K and the other groups (K×6, 436 ± 52 N; K×10, 419 ± 34 N; P < .05). Most specimens failed by rupture of the suture thread in group K. Pullout of the suture from the tendon was observed most in groups B and W. The Krackow stitch was superior to other stitch methods. There was, however, no significant effect of the number of throws on the holding strength. The Krackow stitch could prevent suture slippage by a locking mechanism. The whipstitch is not suitable for clinical application even with an increased number of throws.


Quality of healthcare services and its relationship with patient safety culture and nurse-physician professional communication.
Background: This study investigated quality of healthcare services from patients' perspectives and its relationship with patient safety culture and nurse-physician professional communication. Methods: A cross-sectional study was conducted among 300 surgery patients and 101 nurses caring them in a public hospital in Tabriz-Iran. Data were collected using the service quality measurement scale (SERVQUAL), hospital survey on patient safety culture (HSOPSC) and nurse physician professional communication questionnaire. Results: The highest and lowest mean (±SD) scores of the patients' perception on the healthcare services quality belonged to the assurance 13.92 (±3.55) and empathy 6.78 (±1.88) domains,respectively. With regard to the patient safety culture, the mean percentage of positive answers ranged from 45.87% for "non-punitive response to errors" to 68.21% for "organizational continuous learning" domains. The highest and lowest mean (±SD) scores for the nurse physician professional communication were obtained for "cooperation" 3.44 (±0.35) and "non-participative decision-making" 2.84 (±0.34) domains, respectively. The "frequency of reported errors by healthcare professionals" (B=-4.20, 95% CI = -7.14 to -1.27, P<0.01) and "respect and sharing of information" (B=7.69, 95% CI=4.01 to 11.36, P<0.001) predicted the patients'perceptions of the quality of healthcare services. Conclusion: Organizational culture in dealing with medical error should be changed to non-punitive response. Change in safety culture towards reporting of errors, effective communication and teamwork between healthcare professionals are recommended.


Human eosinophil chemotaxis and selective in vivo recruitment by sphingosine 1-phosphate.
Sphingosine 1-phosphate (S1P) is a sphingolipid mediator that is involved in diverse biological functions. Local administration of S1P causes inflammation coupled to a large eosinophil (EO) recruitment in the rat-paw tissue. The inflammatory response is accompanied by an increase in S1P receptors, namely S1P(1), S1P(2), S1P(3), and by an enhanced expression of CCR3, which is the main chemokine receptor known to be involved in EO function. Human EOs constitutively express S1P(1) and, at a lower extent, S1P(2), S1P(3) receptors. S1P in vitro causes cultured human EO migration and an increase in S1P receptor mRNA copies and strongly up-regulates CCR3 and RANTES (regulated on activation, normal T cell-expressed and secreted) message levels; in particular CCR3 is up-regulated 18,000-fold by S1P. A blocking anti-CCR3 Ab inhibits S1P-induced chemotaxis, implying that S1P acts as specific recruiting signal for EOs not only through its own receptors but also through CCR3. These results show that S1P is involved in EO chemotaxis and contribute to shed light on the complex mechanisms underlying EO recruitment in several diseases such as asthma and some malignancies.


Diet and adjuvant-induced arthritis in the rat.
Rats fed a high carbohydrate or a high protein diet deficient in copper, magnesium or zinc, or in the three trace elements together, failed to develop adjuvant-induced arthritis, yet a deficiency of both copper and magnesium in the diets exhibited no such inhibition. On the other hand, only a magnesium deficiency reduced the severity of the dextran anaphylactoid reaction.


[Puerperal and non-puerperal mastitis].
Report about 82 women with inflammatory breast diseases, who were hospitalized during january 1988 and december 1993. 37 women had a puerperal mastitis, 39 women a non-puerperal mastitis and 6 had perimamillary abscesses. In 35 (42.7%) of the 82 patients abscesses occurred. The different etiology and bacteriology as well as resulting treatment guidelines are discussed. In the treatment of puerperal mastitis, staphylococcus effective penicillins keep the first place. The therapy of non-puerperal mastitis consists in prolactin inhibiting drugs and broad spectrum antibiotics. In abscesses and fistulas surgical treatment is necessary, the same in recurrences. If the process is suspicious for breast cancer diagnostic excision is to perform.


Influence of Pd codeposition on the magnetic properties of Co particles on alumina/NiAl110.
Changes of the magnetic properties of ferromagnetic Co particles deposited at room temperature on a thin alumina film grown on a NiAl(110) substrate were investigated as a function of Pd coverage by subsequent deposition of Pd onto deposited Co particles. From previous x-ray photoelectron spectroscopy, IR, and temperature programmed desorption experiments it was concluded that Pd forms a shell on top of Co particles. However, the current experiments indicate that Pd does induce structural rearrangements within the Co particles which may also involve the intermixing of small amounts of Pd into the Co particles. The latter is inferred from a change in the g-value for small particles. The impact of a larger intermixture of Co and Pd on the magnetic properties will be emphasized by a reversed deposition order where Pd particles were deposited first and subsequently covered by Co. The reversal of the deposition order increases the magnetic anisotropy of the particles considerably.


Rapid ejection of giant Pluronic L121 vesicles from spreading double emulsion droplets.
We report the formation of giant Pluronic L121 vesicles with diameters of the order of 200 microm obtained by a previously unreported mechanism that occurs during the solvent evaporation method of vesicle formation. We begin with a water-oil-water double emulsion that is stabilized by dissolving the commercially available triblock copolymer Pluronic L121 in the volatile oil-phase. During the evaporation, the oil phase spreads on the surface of the continuous aqueous phase, leaving behind the aqueous inner droplet of the double emulsion droplet that eventually yields the vesicle. The spreading of the solvent mixture of the oil phase is induced either by the rapid ejection of the inner droplet out of the double emulsion droplet, or by the spreading of the oil phase of a neighboring emulsion droplet.


Association between the total fertility rate and under-five child sex ratio in India: a panel study among districts of the major states.
This study examined the relationship between the total fertility rate and under-five child sex ratio to understand the role of fertility in the phenomenon of missing girls in India. Using data from the last four decennial censuses for the fifteen major states of India and their districts, covering more than 90% of the population of India, the study showed that there was a major decline in the female to male child sex ratio from 1981 to 2011 in most of the major Indian states and their districts. The panel regression model showed that the total fertility rate was significantly associated with the under-five child sex ratio at the district level for the 30-year period from 1981 to 2011 in India, even after controlling for other factors and any other unobserved heterogeneity. This indicates that areas of India with the highest fertility had the higher female to male child sex ratio, while low-fertility districts had a more male-biased sex ratio.


Thyroid Involvement in Hepatitis C Virus-Infected Patients with/without Mixed Cryoglobulinemia.
Thyroid involvement is a common condition that can be recorded during the natural course of different systemic rheumatic diseases, including the mixed cryoglobulinemia (MC) syndrome or cryoglobulinemic vasculitis. MC is triggered by hepatitis C virus (HCV) chronic infection in the majority of cases; it represents the prototype of autoimmune-lymphoproliferative disorders complicating a significant proportion of patients with chronic HCV infection. HCV is both hepato- and lymphotropic virus responsible for a great number of autoimmune/lymphoproliferative and/or neoplastic disorders. The complex of HCV-related hepatic and extrahepatic manifestations, including MC and thyroid involvement, may be termed "HCV syndrome." Here, we describe the prevalence and clinico-serological characteristics of thyroid involvement, mainly autoimmune thyroiditis and papillary thyroid cancer, in patients with HCV syndrome with or without cryoglobulinemic vasculitis.


A cross-sectional seroepidemiological survey of typhoid fever in Fiji.
Fiji, an upper-middle income state in the Pacific Ocean, has experienced an increase in confirmed case notifications of enteric fever caused by Salmonella enterica serovar Typhi (S. Typhi). To characterize the epidemiology of typhoid exposure, we conducted a cross-sectional sero-epidemiological survey measuring IgG against the Vi antigen of S. Typhi to estimate the effect of age, ethnicity, and other variables on seroprevalence. Epidemiologically relevant cut-off titres were established using a mixed model analysis of data from recovering culture-confirmed typhoid cases. We enrolled and assayed plasma of 1787 participants for anti-Vi IgG; 1,531 of these were resident in mainland areas that had not been previously vaccinated against S. Typhi (seropositivity 32.3% (95%CI 28.2 to 36.3%)), 256 were resident on Taveuni island, which had been previously vaccinated (seropositivity 71.5% (95%CI 62.1 to 80.9%)). The seroprevalence on the Fijian mainland is one to two orders of magnitude higher than expected from confirmed case surveillance incidence, suggesting substantial subclinical or otherwise unreported typhoid. We found no significant differences in seropositivity prevalences by ethnicity, which is in contrast to disease surveillance data in which the indigenous iTaukei Fijian population are disproportionately affected. Using multivariable logistic regression, seropositivity was associated with increased age (odds ratio 1.3 (95% CI 1.2 to 1.4) per 10 years), the presence of a pit latrine (OR 1.6, 95%CI 1.1 to 2.3) as opposed to a septic tank or piped sewer, and residence in settlements rather than residential housing or villages (OR 1.6, 95% CI 1.0 to 2.7). Increasing seropositivity with age is suggestive of low-level endemic transmission in Fiji. Improved sanitation where pit latrines are used and addressing potential transmission routes in settlements may reduce exposure to S. Typhi. Widespread unreported infection suggests there may be a role for typhoid vaccination in Fiji, in addition to public health management of cases and outbreaks.


Investigating the Al/Si mixed site occupancy in the β-AlFeSi phase.
This work investigates the mixed site occupancy of aluminium and silicon atoms in the β-AlFeSi phase. For this purpose, the six mixed Al/Si sites of the β-AlFeSi structure were considered independent and alternatively substituted by Al or Si, thus generating 64 ordered structures or end-members. The enthalpy of formation of each end-member was calculated by DFT. These calculations allowed us to derive the enthalpy of mixing of the solid solution at 0 K, over a wide range of chemical compositions, from the Al-Fe binary system to the Si-Fe binary system. In addition, the heat capacities of the solid solution were determined using a Debye model based on the calculation of the elastic constants and the equation of state of each end-member. These heat capacity values were used along with the enthalpy of formation we calculated to determine the Gibbs free energies of all the end-members of the β-AlFeSi structure. Finally, the configurational entropy of mixing from the Compound Energy Formalism (CEF) for the configurational entropy of mixing was subsequently used to calculate the occupation fractions of the Si sites on the Al sites of the β-AlFeSi structure, at 300 K and 938 K, the latter being the thermal decomposition temperature of this compound. These original site occupancy data were used to quantify the chemical ordering of the solid solution and to compare different sublattice (SL) models. We thus highlight that the SL model of the β-AlFeSi solution most commonly accepted in the literature generates considerable errors in its thermodynamic description, contrary to the model proposed in this paper, which is both simple and particularly accurate, consisting in merging the sites Al(1)-Al(6), the sites Al(2)-Al(3) as well as the sites Al(4)-Al(5).


Use of patient-controlled analgesia with critically ill patients: a risk/benefit analysis.
Patient-controlled analgesia (PCA), a system by which patients self-administer intravenous doses of narcotics using specially programmed infusion pumps, has been used for pain management in acute care settings for nearly two decades. The safety and effectiveness of PCA has been documented in many acutely ill patient populations. Its introduction into critical care practice in the last five years has provided an important adjunct to traditional methods of pain management. However, intravenous narcotics of any type can provoke hemodynamic or respiratory complications in these compromised patients. Nursing expertise is a key factor in the successful implementation of PCA in critically ill patients.


Radioimmunotherapy-based conditioning regimen prior to autologous stem cell transplantation in non-Hodgkin lymphoma.
Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy and the sixth cause of death from cancer in the USA. Autologous stem cell transplantation (ASCT) is a potentially curative therapeutic option for many NHL patients. Choosing the most effective conditioning regimen prior to ASCT can lead to longer survival in these patients, and, as in many cases of high risk NHL, the only potentially curative option is stem cell transplantation. Radioimmunotherapy (RIT) is based on using radiolabeled monoclonal antibodies against tumoral antigens. Since lymphoma cells are sensitive to radiation, RIT has become a potential approach in treating NHL. In this review, we have discussed the efficacy and safety of RIT as an alternative conditioning regimen prior to ASCT.


The growth cycle of influenza viruses as studied in touch preparations of the allantoic layer of chick embryos. 2. The morphology of allantoic cells infected by influenza A virus.
The morphology of allantoic cells infected by influenza A virus was studied in touch preparations of the allantoic layer from 11-day embryos inoculated by the intra-allantoic route. Two comparative doses were used: 10(9) ID50 or large inocula (multiplicity: 100 ID50 to 3 cells) and 200 ID50 (multiplicity: 1 ID50 to 150,000 cells) or small inocula. The allantoic layer from 11-day eggs is an epithelium consisting of at least two strats: a superficial stratum and a deep one. Both with the large and the small inocula, a total and irreversible destruction of the superfifial stratum (cells having free facets in ocntact wit- allantoic fluid) was produced, while the profound one (a layer underlying the surface stratum, with cells normally not having any contact with the allantoic fluid) remained essentially intact. Three successive stages were observed. 1. Incubation period: The cells of both strata exhibited a normal appearance during the first 10 hours with the higher multiplicity, and for the first 15-17 hours with the lower multiplicity. 2. Necrotic period: The cells of the superficial stratum exhibited degenerative changes (the chromatin breaks up into numerous irregular and deeply stained fragments) followed by desquamation into the allantoic fluid within the next 10 hours (from 10th to 20-22th hour after inoculation) with the large, and the next 17 hours (from 15th-17th to 32nd-34th h.) with the small inocula. No morphological changes were observed with the profound cells. 3. Post-necrotic period: The profound stratum with cells of sound appearance, some of whoch showed giant nuclei (polyploid cells?) REMAINED UNTIL THE DEATH OF THE EMBRYos which occurred within a maximum of 6-7 days after inoculation. Occasionally, throughout this period, degenerated deep cells were found (about 1-5% in quantity) which, with the aid of immunofluorescence procedure, are believed to be related to a minor cycle of virus multiplication.


[Spontaneous cutaneous umbilical endometriosis].
Endometriosis consists of extrauterine endometrial growths. Although it is usually located in the pelvis it can also be found in other sites. Endometriosis of the skin is rare and the most frequent form develops over gynecologic or obstetric scars, although it may also appear spontaneously in the umbilical area. We present a 39-years-old woman with an umbilical nodule as a clinically characteristic form of spontaneous cutaneous endometriosis. The histopathological examination confirmed the clinical diagnosis.


Pathology testing in the tired patient--a rational approach.
Pathology tests are often ordered by general practitioners to investigate patients with nonspecific complaints such as malaise and tiredness. This article looks at the tests ordered regularly by GPs to investigate tiredness, the value of these tests, and why these tests are ordered in general practice. General practitioners investigate about half of all tired patients, and most commonly on the first encounter. Tiredness accounts for 4.6% of pathology tests and 2.3% of the growth in pathology testing requested by GPs. Typical pathology tests requested in this circumstance are FBC, EUC, TSH, ferritin and LFTs. Investigations are usually performed to exclude diagnosis and reassure the patient. However, these tests have a low pick up rate of serious disease. More research is needed to establish best practice in the investigation of the tired patient. Future evidence based guidelines should be simple, evidence based and targeted at the general practice experience of patient care.


Dental management of patients with Alzheimer's disease.
This article reviews the recent literature regarding the epidemiology, etiology, pathophysiology, diagnosis, and treatment of Alzheimer's disease. The dental management of patients with Alzheimer's disease is discussed in some detail.


High-voltage dentistry: modern clinical applications for an ancient dental device.
In the early 1900s, a new high-energy device was introduced as a cure-all for a multitude of diseases and conditions that afflicted the population. Dental pain and disease were among those treatable ailments. Treatment consisted of applying direct contact to the body with a handheld, high-voltage Tesla Coil and Geissler tube, which created heat, ozone, and ultraviolet light (UV), termed the "Violet Ray" This treatment was considered mostly a fraud and banned by the Food and Drug Administration (FDA) in 1950.


Statin use and the risk of liver cancer: a population-based case–control study.
Experimental studies have shown that statins have potential protective effects against cancer. The aim of this study was to investigate whether the use of statins was associated with liver cancer risk. We conducted a population-based case–control study in Taiwan. Data were retrospectively collected from the Taiwan National Health Insurance Research Database. Cases consisted of all patients who were aged ≥50 years and had a first-time diagnosis of liver cancer for the period between 2005 and 2008. Controls were pair matched to cases by age, sex, and index date. Adjusted odds ratios (ORs) and 95% CIs (95% confidence intervals) were estimated using multiple logistic regression. We examined 1,166 liver cancer cases and 1,166 controls. Compared with the group with no use of statins, the adjusted ORs were 0.62 (95% CI=0.42-0.91) for the group having been prescribed statins below 215.4 defined daily dose (DDD) and 0.63 (95% CI=0.37-1.06) for the group with cumulative statin use ≥215.4 DDD. The ORs for the group with cumulative statin use ≥215.4 DDD were not statistically significant, but this may be due to the relatively small number of subjects. The results of this study suggest that statins may reduce the risk of liver cancer.


Two platinum(ii) complexes with a 4-phenyl-4H-1,2,4-triazole derivative as an ancillary ligand for efficient green OLEDs.
Two new cyclometalated platinum(ii) complexes ((TN3T)Pt(dptp), (4tfmppy)Pt(dptp)) with 2',6'-bis(trifluoromethyl)-2,3'-bipyridine (TN3T) and 4-trifluoromethylphenylpyridine (4tfmppy) as the cyclometalated ligands and the nitrogen heterocycle 2-(4,5-diphenyl-4H-1,2,4-triazol-3-yl)phenol (dptp) as the ancillary ligand were developed. Both complexes are green phosphors with high photoluminescence quantum efficiency yields (λmax = 532 nm, Φp = 65% for (TN3T)Pt(dptp) and λmax = 502 nm, Φp = 71% for (4tfmppy)Pt(dptp)) in CH2Cl2 solutions at room temperature, respectively. Organic light-emitting diodes (OLEDs) with single-emitting layer and double-emitting layer structures were fabricated with good performances. Particularly, the double-emitting layer device D2 based on the complex (4tfmppy)Pt(dptp) with 6 wt% doped concentration shows superior performances with a maximum EQE of 26.90% with mild efficiency roll-off. This study demonstrates that the ancillary ligand attached with a 4-phenyl-4H-1,2,4-triazole group could facilitate charge trapping across the bulk of the device for efficient OLEDs.


The value of the presence of social work in emergency departments.
The value of the presence of social work in emergency rooms is supported by directly examining the hospitalization rates of patients seen by social workers. It utilizes a 3-year-long data set of social work self-reports on medical emergency room outcomes at a large, teaching hospital in the New York Metropolitan area with a sample size of 3370. The study findings suggest that social workers in this acute care hospital's emergency room often are referred the most complex cases. The data on this site indicate that the majority of social work dispositions were to home (54%) or a nursing facility (8.4%). Only 16% of the patients seen by social work were admitted to the hospital. These findings support the cost-effective nature of social work in the emergency room setting and the importance of finding alternatives to hospital admissions. The results of a logistic regression suggest that the criteria used by social workers to assess patients are based on sound psychosocial factors. Patients who were assessed as having "Environmental" (p = .00) or "Relationship" problems (p = .00) were much less likely to be admitted. Conversely, patients with "Care/ADL" problems (p = .00) and behavior problems (p = .00) had a heightened chance of being admitted. Being African American has less effect but was still relevant.


Involvement of glycogen debranching enzyme in bladder cancer.
Bladder cancer is the most common malignancy of the urinary system, however the molecular pathways underlying this disease are incompletely understood. To understand new regulators of bladder cancer progression, the authors carried out a functional genomic screen which identified glycogen debranching enzyme (AGL) as a novel regulator of bladder cancer growth. Glycogen debranching enzyme is involved in glycogen breakdown and germline loss of function mutation of this gene leads to glycogen storage disease type III. To the best of the authors' knowledge, the present study is the first to demonstrate that loss of AGL leads to aggressive bladder tumor growth. AGL mRNA and protein expression in bladder tumors serve as a prognostic marker for patients. Interestingly, AGL's participation in regulating tumor growth is independent of its enzymatic function and involvement with glycogen metabolism in general. Detailed metabolomics and transcriptomic analysis indicated that increases in glucose metabolism, glycine synthesis driven by serine hydroxymethyltransferase 2 and increases in hyaluronic acid synthase 2-driven HA synthesis are major contributors of aggressive bladder tumor growth with loss of AGL. However, the detailed mechanism of how AGL regulates the above mentioned metabolic and genetic pathways is unknown and is being investigated. The present review focuses on AGL's involvement in bladder cancer.


Bisoprolol therapy does not reduce right ventricular sympathetic activity in pulmonary arterial hypertension patients.
Right ventricular (RV) function and autonomic dysfunction are important determinants of morbidity and mortality in patients with pulmonary arterial hypertension (PAH). Although successful in animal studies, effects of beta-blocker therapy on RV function in clinical trials were disappointing. To understand this discrepancy, we studied whether beta-blocker therapy changes RV sympathetic activity. Idiopathic PAH (IPAH) patients received beta-blocker therapy (uptitrated to a maximal tolerated dose) and underwent cardiac magnetic resonance imaging, right heart catheterization, and a [11C]-hydroxyephedrine positron emission tomography ([11C]HED PET) scan at baseline to determine, respectively, RV ejection fraction (RVEF), RV pressures, and sympathetic activity. [11C]HED, a norepinephrine analogue, allows determination of sympathetic innervation of the RV. [11C]HED retention index reflects norepinephrine transporter activity. As a consequence of excessive catecholamine levels in the synaptic cleft, this transporter may be downregulated. Therefore, low [11C]HED retention index indicates high sympathetic activity. 13 IPAH patients underwent [11C]HED PET scans at baseline and after bisoprolol treatment. Although heart rate was reduced, systemic modulation of autonomic activity by bisoprolol did not affect local RV sympathetic nerve activity, RV function, or RV wall tension. In PAH patients, RV [11C]HED retention index was lower compared to LV tracer uptake (p<0.01) and was related to systolic wall tension (R2 = 0.4731, p<0.01) and RV function (R2 = 0.44, p = 0.01). In RV failure, the tolerated dosage of bisoprolol did not result in an improvement of RV function nor in a reduction in RV sympathetic activity.


Maxillofacial infections in lithuanian hospitalised children and adolescents: a 17-years retrospective study.
To analyse the epidemiology, treatment, and microbiological findings of hospitalised Lithuanian children and adolescents admitted due to maxillofacial infections over a 17-years period. 428 medical records of paediatric (under the age of 18) patients hospitalised at Vilnius University Hospital from 2003 to 2019 due to a maxillofacial infection were reviewed. The data concerning patient sociodemographic characteristics, aspects related to a hospital stay, treatment modalities, microbiological findings, and sensitivity to antibiotics, were collected and analysed. The most prevalent condition was odontogenic maxillofacial space infection (28.7%), followed by lymphadenitis (21.7%). The mean (sd) age was 10.86 (4.8) years and the male-to-female ratio was 1.37:1. The majority of patients (83.4%) underwent surgical treatment. The mean (sd) hospital stay was 5.49 (2.9) days. The longest hospital stay was observed in the case of odontogenic maxillofacial space infections. A longer period of hospitalisation was generally associated with the presence of anaerobes and their resistance to antibiotics as well as multiple space involvement in deep neck space infections and a permanent causative tooth in odontogenic cases. The most commonly isolated microbiological species was Staphylococcus aureus spp. The most common origin of maxillofacial infection was odontogenic among investigated Lithuanian children and adolescents. In the majority of cases, a penicillin group antibiotic was prescribed. Streptococci were the predominant bacteria in the cases of odontogenic infection, while Staphylococci were the most prevalent among non-odontogenic cases. Nearly 40.0% of isolated microorganisms were resistant to penicillin. High resistance to metronidazole was identified among anaerobic bacteria.


Therapeutic Potential of CKD-504, a Novel Selective Histone Deacetylase 6 Inhibitor, in a Zebrafish Model of Neuromuscular Junction Disorders.
The neuromuscular junction (NMJ), which is a synapse for signal transmission from motor neurons to muscle cells, has emerged as an important region because of its association with several peripheral neuropathies. In particular, mutations in GARS that affect the formation of NMJ result in Charcot-Marie-Tooth disease and distal hereditary motor neuropathy. These disorders are mainly considered to be caused by neuronal axon abnormalities; however, no treatment is currently available. Therefore, in order to determine whether the NMJ could be targeted to treat neurodegenerative disorders, we investigated the NMJ recovery effect of HDAC6 inhibitors, which have been used in the treatment of several peripheral neuropathies. In the present study, we demonstrated that HDAC6 inhibition was sufficient to enhance movement by restoring NMJ impairments observed in a zebrafish disease model. We found that CKD-504, a novel HDAC6 inhibitor, was effective in repairing NMJ defects, suggesting that treatment of neurodegenerative diseases via NMJ targeting is possible.


[Clinical, morphological and biochemical prognostic factors in acute pancreatitis].
Acute pancreatitis is a potentially lethal disease and mortality depends on severity. The clinical spectrum of acute pancreatitis depends greatly on whether or not pancreatic necrosis is present and to what extend. The effectiveness of any treatment is related to the ability to early predict severity, but there is still no ideal predictive system or biochemical marker. An early enthusiasm over several biochemical markers has diminished because of the costs and impracticability of routine use. Undoubtedly, inflammatory mediators do appear capable of offering greater accuracy, speed and flexibility than older systems but they still require more improvement. Nowadays, prediction of acute pancreatitis severity is based on compilation of methods--clinical assessment, use of multifactor score system, measurement of biochemical markers and computed tomography.


Chronic Thromboembolic Pulmonary Hypertension Complicated by Giant Pulmonary Artery Aneurysm.
A pulmonary artery (PA) aneurysm is an extremely rare condition that can be idiopathic or secondary. Only a few reports on giant PA aneurysms associated with chronic thromboembolic pulmonary hypertension (CTEPH) are available in the literature. Here, we present a case of CTEPH associated with a secondary giant PA aneurysm detected by autopsy. A 68-year-old woman was diagnosed with pulmonary hypertension (PH) and a PA aneurysm with a diameter of 7.5 cm 7 years before admission. CTEPH was suspected as the cause of PH; however, she refused to undergo surgical treatment. Although her condition improved temporarily with pulmonary vasodilators, she had recurrence of heart failure and died because of the deterioration of her general condition. An autopsy revealed a giant PA aneurysm without medial degeneration, suggesting a secondary PA aneurysm associated with PH. Histological findings indicated multiple organized thrombi with recanalization in the PA bilaterally, and CTEPH was diagnosed as the cause of PH. Although rare, when a PA aneurysm is detected, it is important to consider that CTEPH might be associated with a giant PA aneurysm. A better understanding of this condition is necessary to improve the therapeutic strategy.


Unusual Defect-Related Room-Temperature Emission from WS2 Monolayers Synthesized through a Potassium-Based Precursor.
Alkali-metal-based synthesis of transition metal dichalcogenide (TMD) monolayers is an established strategy for both ultralarge lateral growth and promoting the metastable 1T phase. However, whether this can also lead to modified optical properties is underexplored, with reported photoluminescence (PL) spectra from semiconducting systems showing little difference from more traditional syntheses. Here, we show that the growth of WS2 monolayers from a potassium-salt precursor can lead to a pronounced low-energy emission in the PL spectrum. This is seen 200-300 meV below the A exciton and can dominate the signal at room temperature. The emission is spatially heterogeneous, and its presence is attributed to defects in the layer due to sublinear intensity power dependence, a noticeable aging effect, and insensitivity to washing in water and acetone. Interestingly, statistical analysis links the band to an increase in the width of the A1g Raman band. The emission can be controlled by altering when hydrogen is introduced into the growth process. This work demonstrates intrinsic and intense defect-related emission at room temperature and establishes further opportunities for tuning TMD properties through alkali-metal precursors.


Polymerase and exonuclease activities in herpes simplex virus type 1 DNA polymerase are not highly coordinated.
The herpes polymerase-processivity factor complex consists of the catalytic UL30 subunit containing both polymerase and proofreading exonuclease activities and the UL42 subunit that acts as a processivity factor. Curiously, the highly active exonuclease has minimal impact on the accumulation of mismatches generated by the polymerase activity. We utilized a series of oligonucleotides of defined sequence to define the interactions between the polymerase and exonuclease active sites. Exonuclease activity requires unwinding of two nucleotides of the duplex primer-template. Surprisingly, even though the exonuclease rate is much higher than the rate of DNA dissociation, the exonuclease degrades both single- and double-stranded DNA in a nonprocessive manner. Efficient proofreading of incorrect nucleotides incorporated by the polymerase would seem to require efficient translocation of DNA between the exonuclease and polymerase active sites. However, we found that translocation of DNA from the exonuclease to polymerase active site is remarkably inefficient. Consistent with inefficient translocation, the DNA binding sites for the exonuclease and polymerase active sites appear to be largely independent, such that the two activities appear noncoordinated. Finally, the presence or absence of UL42 did not impact the coordination of the polymerase and exonuclease activities. In addition to providing fundamental insights into how the polymerase and exonuclease function together, these activities provide a rationale for understanding why the exonuclease minimally impacts accumulation of mismatches by the purified polymerase and raise the question of how these two activities function together in vivo.


Long-term culture of hamster duodenal explants and cells.
Explants from adult Syrian hamster duodenum have been maintained in organ culture on gelatin sponges using CMRL 1066 serum supplemented media for 30 days. There was necrosis of the tall villi architecture during the 1st week in culture while columnar and mucous cells survived, migrated, and replicated along portions of the explant basement membrane and in the gelatin sponge matrix. Cells in the sponge multiplied and formed epithelial sheets which showed villus projections and cyst configurations. The cells in these epithelial structures were attached to one another by junctional complexes. Epithelial cells were isolated from the sponge matrix by collagenase digestion and were successfully grown in culture. These duodenal explants and cells show potential for use as in vitro models for experimental studies, involving acute and chronic response of cells to injury or carcinogen-induced transformation.


Cleft lip and/or palate in two cases of 46,X,i(Xq) Turner syndrome.
Cleft lip (CL) and/or palate (CP) are uncommon anomalies in Turner syndrome (TS) series. We report two unrelated sporadic 46,X,i(Xq) patients exhibiting orofacial clefts and a peculiar facial appearance masking the clinical diagnosis. CL, and CP in case 1 and CP in case 2, though non-specific of TS, may not be fortuitous findings. The increased frequency of CP and bifid uvula in poly X syndromes, the dermatoglyphic similarities between iXq TS and X polysomies, and the occurrence of Klinefelter phenotype when extra Xq material is present in a male, are all indirect evidences suggesting that Xq material cannot be considered phenotipically inert and facial clefts found in our patients may be syndromal manifestation of trisomic Xq dosage.


Transition from an electron solid to the sequence of fractional quantum Hall states at very low Landau level filling factor.
At low Landau level filling of a two-dimensional electron system, typically associated with the formation of an electron crystal, we observe local minima in Rxx at filling factors nu = 2/11, 3/17, 3/19, 2/13, 1/7, 2/15, 2/17, and 1/9. Each of these developing fractional quantum Hall (FQHE) states appears only above a filling-factor-specific temperature. This can be interpreted as the melting of an electron crystal and subsequent FQHE liquid formation. The observed sequence of FQHE states follows the series of composite fermion states emanating from nu = 1/6 and nu = 1/8.


Effect of colored noises on spatiotemporal chaos in the complex Ginzburg-Landau equation.
The effect of colored noises, which are correlated both in space and time, on spatiotemporal chaos in the complex Ginzburg-Landau equation has been studied numerically. The correlations of spatiotemporal patterns as a function of characteristics of noise were calculated. We found that there exists an optimal correlation length of noise where the system establishes its maximal spatial correlation; a small temporal correlation of noise corresponds to a larger correlation length in the system; and that an increase of noise intensity enhances the spatial correlation of the spatiotemporal patterns. Besides, the frequency of temporal correlation function, which is a complicated oscillation, also depends on properties of the noise.


Stimulation of AMP-activated protein kinase is essential for the induction of drug metabolizing enzymes by phenobarbital in human and mouse liver.
Our previous studies have suggested a role for AMP-activated protein kinase (AMPK) in the induction of CYP2B6 by phenobarbital (PB) in hepatoma-derived cells (Rencurel et al., 2005). In this study, we showed in primary human hepatocytes that: 1) 5'-phosphoribosyl-5-aminoimidazol-4-carboxamide 1-beta-d-ribofuranoside and the biguanide metformin, known activators of AMPK, dose-dependently increase the expression of CYP2B6 and CYP3A4 to an extent similar to that of PB. 2) PB, but not the human nuclear receptor constitutive active/androstane receptor (CAR) ligand 6-(4-chlorophenyl)imidazol[2,1-6][1,3]thiazole-5-carbaldehyde, dose-dependently increase AMPK activity. 3) Pharmacological inhibition of AMPK activity with compound C or dominant-negative forms of AMPK blunt the inductive response to phenobarbital. Furthermore, in transgenic mice with a liver-specific deletion of both the alpha1 and alpha2 AMPK catalytic subunits, basal levels of Cyp2b10 and Cyp3a11 mRNA were increased but not in primary culture of mouse hepatocytes. However, phenobarbital or 1,4 bis[2-(3,5-dichloropyridyloxy)]benzene, a mouse CAR ligand, failed to induce the expression of these genes in the liver or cultured hepatocytes from mice lacking hepatic expression of the alpha1 and alpha2 subunits of AMPK. The distribution of CAR between the nucleus and cytosol was not altered in hepatocytes from mice lacking both AMPK catalytic subunits. These data highlight the essential role of AMPK in the CAR-mediated signal transduction pathway.


Anticancer Effect of Thymol on AGS Human Gastric Carcinoma Cells.
Numerous plants have been documented to contain phenolic compounds. Thymol is one among these phenolic compounds that possess a repertoire of pharmacological activities, including anti-inflammatory, anticancer, antioxidant, antibacterial, and antimicrobial effects. Despite of the plethora of affects elicited by thymol, its activity profile on gastric cancer cells is not explored. In this study, we discovered that thymol exerts anticancer effects by suppressing cell growth, inducing apoptosis, producing intracellular reactive oxygen species, depolarizing mitochondrial membrane potential, and activating the proapoptotic mitochondrial proteins Bax, cysteine aspartases (caspases), and poly ADP ribose polymerase in human gastric AGS cells. The outcomes of this study displayed that thymol, via an intrinsic mitochondrial pathway, was responsible for inducing apoptosis in gastric AGS cells. Hence, thymol might serve as a tentative agent in the future to treat cancer.


A novel genetic marker of the ovomucoid gene associated with hatchability in Tsaiya ducks (Anas platyrhynchos).
Transcriptome analysis using a cDNA microarray was performed to identify differentially expressed genes that are correlated with hatchability, and a new PCR-RFLP marker of high hatchability among the identified genes was observed. We used the cDNA microarray technique for gene expression profiling of the magnum epithelium of laying Tsaiya ducks, and several regulated genes associated with hatchability were found. The results of real-time PCR and Western blotting analysis confirmed that the mRNA and protein levels of ovomucoid in the magnum epithelium of animals in the low-hatchability group were significantly higher than the levels in the high-hatchability group (P < 0.05). Primers TovF1 and TovR1, designed according to the ovomucoid EST sequence, were used to amplify genomic DNA samples of different individual Tsaiya ducks, and sequence analysis of the amplified DNA products showed deletion among the ducks from the low-hatchability group. Primers TovF2 and TovR2 were used to perform PCR-RFLP analysis on the amplified DNA products to classify the ducks into +/+, +/- and -/- genotypes. The animals of +/+ and +/- genotypes were identified as having significantly higher hatchability than those of the -/- genotype (P < 0.05). In contrast, no differences were observed between genotypes in terms of fertility, duration of fertility, egg weight or total number of eggs. Our results indicated that a novel PCR-RFLP marker of high hatchability, an ovomucoid gene polymorphism, can be used as a genetic marker for marker-assisted selection to improve hatchability in Tsaiya ducks.


Complete and incomplete Drash syndrome: a clinicopathologic study of five cases of a dysontogenetic-neoplastic complex.
Drash syndrome is a complex disorder characterized by abnormal renal function, abnormal sexual differentiation with predisposition to developing gonadal neoplasms, and nephroblastoma. The authors report five cases with various manifestations of this syndrome. Dysgenetic gonads and abnormal sexual differentiation were present in all patients; two had unilateral and two bilateral gonadoblastomas; in addition, one of the latter had a juvenile granulosa cell tumor. Renal failure was present in all patients. One patient had bilateral Wilms' tumor, and one patient had a metanephric hamartoma. Each element of the triad in this syndrome is analyzed with regard to possible pathogenetic mechanisms and current models of carcinogenesis. Cases with complete forms of the syndrome reported in the literature are reviewed. Patients with incomplete forms of the syndrome must be followed carefully because other elements of this complex may become manifest.


A Combined Transcriptomic and Proteomic Approach to Reveal the Effect of Mogroside V on OVA-Induced Pulmonary Inflammation in Mice.
Mogroside V is a bioactive ingredient extracted from the natural food Siraitia grosvenorii which possesses functions that stimulate lung humidification and cough relief activities, but its underlying mechanisms were rarely studied. To estimate its potential protective effect on ovalbumin (OVA)-induced pulmonary inflammation and understand its system-wide mechanism, integrated omics was applied in this study. Mogroside V effectively reduced the levels of IgE, TNF-α, and IL-5 in OVA-induced mice. The results of RNA-seq and data-independent acquisition proteomics approach revealed that 944 genes and 341 proteins were differentially expressed in the normal control group (NC) and ovalbumin-induced control group (OC) and 449 genes and 259 proteins were differentially expressed between the OC and the group treated with 50 mg/kg mogroside V (MV). After a combined analysis of the transcriptome and the proteome, 93 major pathways were screened, and we discovered that mogroside V exerts an anti-inflammation effect in the lung via NF-κB and JAK-STAT, both of which are among the signaling pathways mentioned above. In addition, we found that the key regulatory molecules (Igha, Ighg1, NF-κB, Jak1, and Stat1) in the two pathways were activated in inflammation and inhibited by mogroside V. Thus, mogroside V may be the main bioactivity component in S. grosvenorii that exerts lung humidification and cough relief effects.


Quality improvement practices in clinical and anatomic pathology services. A College of American Pathologists Q-probes study of the program characteristics and performance in 580 institutions.
Participants of the College of American Pathologists Q-Probes program described their quality improvement practices for clinical and anatomic pathology. In 580 institutions, the median time required for a median of 12 indicators of quality was 40 hours/month, with the number of indicators and the time spent directly dependent on bed size (P = .0001). The overwhelming majority of participants reported benefit from their quality improvement programs in terms of patient outcomes, as a management tool, and for risk management. Six indicators in clinical pathology and four indicators in anatomic pathology were used in more than 75% of laboratories, whereas an additional seven indicators in clinical pathology and five in anatomic pathology were used in more than 50% of laboratories. The authors conclude that quality improvement practices are similar among laboratories, and irrespective of increasing regulatory requirements, pathologists and senior laboratory personnel spend large amounts of time for activities that they believe improve the quality of services rendered.


Identification of the Novel Target Genes for Osteosarcoma Therapy Based on Comprehensive Bioinformatic Analysis.
Osteosarcoma is one of the most common primary malignant tumors of the bone and tends to develop in teenage years. Although multitreatments for the diagnosis and therapy of osteosarcoma have been developed, there are still needs of new methods to prevent and treat the osteosarcoma. Here, we performed bioinformatic analysis to screen for the key genes, molecules, and pathways involved in osteosarcoma survival. Four microarray data sets (GSE99671, GSE87624, GSE65071, and GSE28423), which include data from human bone and osteosarcoma samples, were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed mRNAs and miRNAs were identified. Kyoto Encyclopedia of Genes and Genomes enriched pathways, miRNA-mRNA target, gene/disease relationship, and overall survival was elucidated using related websites and software according to bioinformatic analysis protocols. We found three critical genes miR-29c, blood vessel epicardial substance (BVES), and proteasome 20S subunit beta 2 (PSMB2) through the GEO database and predicting miRNA-mRNA target. Among these genes, BVES and PSMB2 presented a high expression level in osteosarcoma based on GSE99671 and GSE87624 data sets, while miR-29c showed a low expression level in osteosarcoma based on GSE65071 and GSE28423 data sets. Furthermore, we found that the high expression level of miR-29c and BVES associated with better prognosis, while highly expressed PSMB2 associated with poor prognosis. The abnormally expressed mRNAs and miRNAs, which were identified by integrated bioinformatic analysis, provided insights into the molecular mechanisms of osteosarcoma. Notably, we found three critical genes that could be used as novel therapeutic targets for preventing or diagnosing osteosarcoma. Finally, PSMB2 may be the target of miR-29c.


Assessment of psychological and social current working conditions in epidemiological studies: experiences from the MUSIC-Norrtälje study.
The aim of this study was to present, evaluate and propose a tool for the assessment of psychosocial working conditions in epidemiological studies. A referent group of the large epidemiological study, the MUSIC-Norrtälje study of musculoskeletal disorders, was used. The respondents were 950 working persons (585 female and 365 male). Self-administered questionnaire and personal interview were used. The responses were subjected to factor analysis. The resulting model had components generated from the demand-control-support model and action theory. The result supported the use of different aspects of psychological job demands. The interview data seemed to be more related to factual exposure and the questionnaire data more to individual perception. The usefulness of the model was supported by associations between the model and psychosomatic symptoms and sleep disturbances. A combination of interview and questionnaire increases the possibility of interpreting the association between working conditions and health and may provide a more effective basis for interventions.


The value of pre-operative aspiration in the diagnosis of an infected prosthetic knee: a retrospective study and review of literature.
The purpose of this study was to compare the results of cultures of preoperative aspiration samples with those of swabs taken intra-operatively. The records of 70 revision arthroplasties of the knee from 69 patients, 49 females and 20 males, were reviewed. The mean age of the patients at time of revision arthroplasty was 67 years (range: 34 to 89). Sixty-eight knees from 67 patients were included. There were 32 true positives, 17 true negatives, 6 false positives and 13 false negatives. This led to a specificity, sensitivity and accuracy of 57%, 84% and 72%, respectively. Based on these findings, pre-operative aspiration has a positive predictive value of 71% and a negative predictive value of 74%. When the aspiration sample yields a positive culture, the chances are high that the prosthetic knee is infected. When aspiration is negative, infection cannot be ruled out. Our study suggests that, in such cases, a coagulase negative Staphylococcus (CNS) infection has to be considered.


Spatio-temporal trends of PCBs in the Swedish freshwater environment 1981-2012.
Polychlorinated biphenyls (PCBs) have been monitored in perch (Perca fluviatilis), pike (Esox lucius), and Arctic char (Salvelinus alpinus) in reference lakes since the late 1960s. Temporal trends and spatial patterns are currently monitored in nine and 32 lakes, respectively. Overall, PCB concentrations are decreasing. However, this is not consistent for all congeners across all lakes and species. Perch has comparatively low PCB concentrations relative to suggested target levels, but individual congener concentrations in some lakes are concerningly high. No temporal trend is seen for CB-118 and CB-153 in perch, but significant decreasing trends exist for Arctic char and pike, for which monitoring started earlier than for perch. The lower/higher chlorinated congener ratio decreased over time in most lakes, indicating fewer new emissions. CB-118 and CB-153 concentrations in perch show spatial gradients across Sweden, with higher concentrations found near urban/industrial areas.


Chimeric VEGF-ENZ7/PlGF specifically binding to VEGFR-2 accelerates skin wound healing via enhancement of neovascularization.
VEGF-E(NZ7)/PlGF molecules composed of Orf virus-derived VEGF-E(NZ7) and human PlGF1 were previously proven to be potent angiogenic factors stimulating angiogenesis without significant enhancement of vascular leakage and inflammation in vivo. For its future clinical application, there is a pressing need to better understand the beneficial effects of VEGF-E(NZ7)/PlGF during wound healing in adulthood. In this study, several angiogenic factors were administrated to skin punched wounds of both wild-type and diabetic mice. The treatment with VEGF-E(NZ7)/PlGF accelerated wound closure accompanied with enhanced angiogenesis, the process was occurring slightly faster than that in VEGF-A164 group. Moreover, the macrophage infiltration and lymphangiogenesis level in healed wounds were strikingly lower in VEGF-E(NZ7)/PlGF group than VEGF-A164 group, suggesting that the increased inflammation was the key issue preventing speedy wound healing of VEGF-A164-treated skin. Considering clinical safety, we further examined the antigenicity of chimeric VEGF-E(NZ7)/PlGF. Compared with the original VEGF-E(NZ7), the immunogenicity of VEGF-E(NZ7)/PlGF molecules was markedly decreased in mice and squirrel monkeys with the increase of PlGF1 humanized ratio. These results indicate that VEGF-E(NZ7)/PlGF molecules are superior to VEGF-A for the acceleration of either normal or delayed skin wound healing and might be regarded as potential drugs in therapeutic angiogenesis.


Airborne fungi induce nasal polyp epithelial cell activation and Toll-like receptor expression.
The nasal epithelium is the first barrier encountered by airborne allergens and is an active participant in airway inflammation. Fungi have been increasingly recognized as important pathogens in sinusitis and airway diseases. The aim of the study was to evaluate fungal protease activity during cytokine production in nasal polyp epithelial cells and to determine the expression of Toll-like receptor (TLR) mRNA by fungi. Nasal polyp epithelial cells were obtained from patients and stimulated with Alternaria and Aspergillus. Interleukin-8 (IL-8) and granulocyte macrophage colony-stimulating factor (GM-CSF) were measured to determine the activation of epithelial cells. Reverse transcriptase polymerase chain reaction for the TLR mRNA expression of the nasal epithelial cells was performed. Cytokine production was inhibited with protease inhibitors and anti-human TLR antibodies. The fungi enhanced the production of IL-8 and GM-CSF from nasal epithelial cells. When nasal epithelial cells were activated by the fungi, TLR2, TLR3 and TLR4 mRNAs were more strongly expressed than in the nonactivated cells. Cytokine production was inhibited by protease inhibitors and anti-human TLR4 antibodies. The results of this study showed that fungi interacted with nasal epithelial cells and enhanced the production of cytokines and TLR mRNA expression. The cytokine production was related to the protease in fungi and TLR4.