A Hydroalcoholic Extract from Paullinia pinnata L. Roots Exerts Anthelmintic Activity against Free-Living and Parasitic Nematodes.
Paullinia pinnata is a medicinal plant traditionally used in West Africa against a wide range of diseases including soil-transmitted helminthiases. In this study, a hydroethanolic root extract was investigated for its phytochemical composition and in vitro activity against the free-living nematode Caenorhabditis elegans as well as the larval stages of the parasitic helminths Ancylostoma caninum, Haemonchus contortus, Toxocara cati, and Trichuris vulpis.LC-MS analysis of the ethanol-water (1 : 1) extract revealed epicatechin and different A-type linked oligomeric and polymeric procyanidins as the predominant compounds.Within an in vitro mortality assay, the extract showed a lethal activity against T. cati (LC50 of 112 µg/mL), T. vulpis (LC50 of 17 µg/mL), and C. elegans (LC50 2.5 of mg/mL), but not against A. caninum. Additionally, effects on egg hatching and larval migration of H. contortus were investigated, but no inhibitory activity was observed.Overall, these findings rationalize the traditional use of the root extract from P. pinnata as an anthelmintic remedy and provide insight into the phytochemical composition of the extract.


Refractoriness of the western fence lizard (Sceloporus occidentalis) to the Lyme disease group spirochete Borrelia bissettii.
The western fence lizard, Sceloporus occidentalis, is refractory to experimental infection with Borrelia burgdorferi sensu stricto, one of several Lyme disease spirochetes pathogenic for humans. Another member of the Lyme disease spirochete complex, Borrelia bissettii, is distributed widely throughout North America and a similar, if not identical, spirochete has been implicated as a human pathogen in southern Europe. To determine the susceptibility of S. occidentalis to B. bissettii, 6 naïve lizards were exposed to the feeding activities of Ixodes pacificus nymphs experimentally infected with this spirochete. None of the lizards developed spirochetemias detectable by polymerase chain reaction for up to 8 wk post-tick feeding, infected nymphs apparently lost their B. bissettii infections within 1-2 wk after engorgement, and xenodiagnostic L. pacificus larvae that co-fed alongside infected nymphs did not acquire and maintain spirochetes. In contrast, 3 of 4 naïve deer mice (Peromyscus maniculatus) exposed similarly to feeding by 1 or more B. bissettii-infected nymphs developed patent infections within 4 wk. These and previous findings suggest that the complement system of S. occidentalis typically destroys B. burgdorferi sensu lato spirochetes present in tissues of attached and feeding I. pacificus nymphs, thereby potentially reducing the probability of transmission of these bacteria to humans or other animals by the resultant adult ticks.


Sulfatides inhibit leukotriene synthesis in human polymorphonuclear granulocytes by a mechanism involving lipid rearrangement in intracellular membranes.
Sulfatides - sulfated derivatives of galactocerebroside - are endogenous ligands for P- and L-selectins and are able to induce intracellular signaling in neutrophils through a L-selectin dependent pathway. Sulfatides are implicated in a variety of physiological functions and have been found to suppress the synthesis of 5-lipoxygenase (5-LO) metabolites and impede 5-LO translocation to the nuclear envelope in adherent human polymorphonuclear leukocytes (PMNs) [Sud'ina, G. F., Brock, T. G., Pushkareva, M. A., Galkina, S. I., Turutin, D. V., Peters-Golden, M., et al. (2001). Sulphatides trigger polymorphonuclear granulocyte spreading on collagen-coated surfaces and inhibit subsequent activation of 5-lipoxygenase. The Biochemical Journal, 359, 621-629]. In this study we investigated the mechanism of the leukotriene (LT) synthesis inhibition by sulfatides. Sulfatides neither attenuated the ionophore-induced rise in [Ca(2+)](i) nor promoted PKA activation. We demonstrated that sulfatides directly inhibited 5-LO enzyme activity in a cell-free assay. BODIPY-labeled sulfatides were able to rapidly penetrate into the cells. Sulfatides induced rearrangement and redistribution of cytoskeletal components in adherent PMNs. The lipid incorporation as well as sulfatide-induced inhibition of LT synthesis were abolished by cytochalasin D, an inhibitor of actin polymerization and endocytosis. Importantly, sulfatides caused a prominent intracellular cholesterol redistribution, increasing its abundance at the uropod region. On the basis of these data, we suggest that increased cholesterol accumulation in cell compartments represents a novel mechanism by which sulfatides abrogate 5-LO translocation and activation.


Scaffold of the cyclooxygenase-2 (COX-2) inhibitor carprofen provides Alzheimer gamma-secretase modulators.
N-sulfonylated and N-alkylated carprofen derivatives were investigated for their inhibition and modulation of gamma-secretase, which is associated with Alzheimer's disease. The introduction of a lipophilic substituent transformed the COX-2 inhibitor carprofen into a potent gamma-secretase modulator. Several compounds (e.g., 9p, 11f) caused selective reduction of Abeta42 and an increase of Abeta38. The most active compounds displayed activities in the low micromolar range and no effect on the gamma-secretase cleavage at the e-site.


The Expanded Programme on Immunization of the World Health Organization.
In the developing world today, less than 20% of children are immunized against diphtheria, pertussis, tetanus, tuberculosis, measles, and poliomyelitis. Consequently, these diseases kill 10 children and disable 10 more each minute. To address this problem, the World Health Organization created the Expanded Programme on Immunization (EPI), with the goal of reducing morbidity and mortality by making immunization services available for all children of the world by 1990. This goal will be difficult to achieve. Information systems and immunization services themselves need to be strengthened. This goal will require commitments by the developing countries of human resources and commitments by developing and developed countries of financial support. Commitment is also needed by parents, who need to be informed that death and disability from these diseases can disappear if their children are immunized. Can these commitments be obtained? There is no choice but to try, for few appeals can be made as powerfully. The EPI cannot be permitted to fail.


Schistosoma mansoni: Natural Infection of Cattle in Brazil.
In an area in Brazil where schistosomiasis has long been endemic, examination of cattle which were slaughtered for food disclosed the presence of adult Schistosoma mansoni in the mesenteric veins of four animals. Eggs of S. mansoni were found in the feces and rectal mucosa of one animal.


[Postoperative acute mitral regurgitation. Unexpected finding after minor non-cardiac surgery].
This report describes the case of a 59-year-old man who was scheduled for general anesthesia with propofol, sufentanil and sevoflurane for removal of a metal implant. The patient was classified as American Society of Anesthesiologists (ASA) II status because of an asymptomatic mitral valve prolapse and medically treated arterial hypertension. During induction of narcosis a pulsoxymetrically measured inadequate increase in oxygen saturation after preoxygenation was noticed and a moderate respiratory obstruction occurred intraoperatively, but anesthesia was uneventfully completed and the patient was extubated. However, 3 h later the patient developed severe dyspnea, hypoxia, tachycardia and arterial hypotension. Physical examination revealed a new grade 4/6 systolic murmur radiating to the axilla and X-ray showed bilateral pulmonary edema. Neither electrocardiographic nor biochemical manifestations of acute myocardial infarction were identified but transthoracic echocardiography revealed fluttering of the posterior leaflet of the mitral valve with grade III regurgitation and dilation of the left atrium. Coronary angiography was normal and left ventriculography confirmed severe mitral regurgitation. Mitral valve repair was successfully performed 22 h after presentation of symptoms. Mitral regurgitation is a common finding on echocardiography, seen to some degree in over 75% of the population. The etiology of mitral valve insufficiency which can be caused by pathologic changes of one or more of the components of the mitral valve, including the leaflets, annulus, chordae tendineae, papillary muscles, or by abnormalities of the surrounding left ventricle and/or atrium are discussed. Rupture of mitral chordae tendineae is infrequent and causes acute hemodynamic deterioration and needs corrective surgery. Valve replacement should be performed only if mitral valve repair is not possible. Echocardiography is an invaluable tool in determining the severity of regurgitation, the integrity of the mitral valve apparatus, the extent of left ventricular enlargement, and the ejection fraction. Acute mitral valve regurgitation caused by a rupture of chordae tendineae should be considered in the differential diagnosis of perioperative acute pulmonary edema.


Epidemiology of Psychiatric Disorders in Children and Adolescents in Chaharmahal and Bakhtiari Province, Iran, 2017.
This study aimed to investigate the epidemiology of psychiatric disorders in children and adolescents in Chaharmahal and Bakhtiari Province of Iran. This community-based cross-sectional study included 1038 children and adolescents aged 6-18 years from Chaharmahal and Bakhtiari province selected by the multistage cluster sampling method. Samples were interviewed using the Schedule for Affective Disorders and Schizophrenia for School-Age Children. Also, demographic data (gender, age, child education, parent education, and economic situation) were obtained. Binary logistic regression was used to analyze the data. A total of 16.1% of participants were diagnosed to have psychiatric disorders. Total psychiatric disorders were significantly more prevalent in boys than in girls (P=0.025). Unemployment of fathers was significantly related to increased prevalence of psychiatric disorders in children (P=0.016). Other demographic variables had no significant correlation with prevalence of psychiatric disorders in children. Anxiety disorders were highly comorbid with behavioral problems (16.4%). Behavioral disorders also had high comorbidity with elimination disorders (16.7%) and substance use disorders (10%). Enuresis was the most frequent psychiatric disorder (5.8%), followed by epilepsy (3.5%), tobacco use (3.4%), and attention deficit hyperactivity disorder (3%). Total anxiety disorders were the most prevalent group of psychiatric disorders in the sample (21.9%), followed by behavioral disorders (16.3%), elimination disorders (8.2%), and neurodevelopmental disorders (4.5%). Our findings suggest that psychiatric disorders affect a significant number of children and adolescents. Prevalence estimates and identification of sources of heterogeneity have important implications to service providers and modifications are needed in mental health services in the community.


Synthesis of Fe3O4/PDA Nanocomposites for Osteosarcoma Magnetic Resonance Imaging and Photothermal Therapy.
Osteosarcomas commonly develop in the metaphysis of the long diaphysis, resulting in pronounced malignancy and high rates of early pulmonary metastasis. At present, osteosarcoma patients exhibit relatively poor survival rates owing these metastases and to the emergence of tumor chemoresistance. As such, there is an urgent need to identify other approaches to treating affected patients. Herein, we synthesized Fe3O4@PDA nanocomposites that exhibited excellent biocompatibility and low toxicity in human and animal model systems. The resultant nanoparticles were able to improve T2 magnetic resonance imaging and to enhance the signal-to-noise ratio associated with osteosarcoma tumors in animal models. Moreover, we were able to successfully leverage these Fe3O4@PDA particles as a photothermal agent capable of significantly inhibiting the growth of tumors and preventing their metastasis to the lung compartment. Together, these results highlight a novel therapeutic platform that has the potential to guide both the more effective diagnosis and treatment of osteosarcoma patients in clinical applications.


Surgical management of organizing pneumonia: a retrospective study of 24 cases in a single Centre.
Organizing pneumonia (OP) is a rare disease that is often easily misdiagnosed as a malignancy. The diagnosis of OP can prove quite challenging. Patients typically receive treatment with high-dose corticosteroids. Relapse is common if corticosteroid treatment is reduced or stopped. However, given that long-term corticosteroid treatment often results in significant side-effects, the aim of this study was to discuss the diagnosis and surgical treatment of OP. The medical records of 24 patients with pathologically diagnosed OP between October 2007 and January 2019 were retrospectively reviewed. All patients underwent thoracic computed tomography (CT) and transbronchial biopsy or CT-guided percutaneous needle aspiration. We analysed the clinical manifestations, radiological findings, diagnostic methods, treatment, and follow-up outcomes of all patients. In total, 24 patients with OP were identified. The study included 17 (70.8%) men and 7 (29.2%) women, and the mean age was 61.25 ± 11.33 years (range: 31-82). The most common symptom was cough (n = 16; 66.6%), and the most common radiological finding was consolidation (n = 13; 54.2%) on thoracic CT. The diagnosis of OP was made by transbronchial biopsy in 11 patients (45.8%), and percutaneous needle aspiration biopsy in 13 (54.2%). We performed 11 wedge resections, 9 segmentectomy, and 4 lobectomies. Twenty patients underwent video-assisted thoracoscopic surgery (VATS), and 4 underwent thoracotomy. Complete lesion resection was obtained in all patients, and all patients were discharged from the hospital between 5 and 11 days after surgery. The mean follow-up period was 59.1 ± 34.5 (range: 2-134) months. Residual lesions or local or distant recurrence were not observed. OP is a rare disease, and the exact aetiology remains unclear. Preoperative diagnosis is difficult to achieve despite the use of transbronchial biopsy or CT-guided percutaneous needle aspiration. Complete surgical resection represents an effective method for the treatment of OP.


B3S2 monolayer as an anode material for Na/K-ion batteries: a first-principles study.
Two-dimensional (2D) materials used as anodes in metal-ion batteries have attracted increased attention due to their high specific surface area, abundant active sites and good electronic properties. Searching for 2D materials with high storage capacities and low diffusion energy barriers is one of the most effective ways to design novel anode materials. In this work, based on first-principles calculations, we design a new 2D B3S2 monolayer with high thermodynamic and dynamic stability. The obtained B3S2 monolayer has a high cohesive energy, ensuring the feasibility of experimental synthesis. These characteristics of the B3S2 monolayer prompt us to explore its application as an anode material. The B3S2 monolayer exhibits not only a metallic nature but also a low diffusion energy barrier (0.037 eV) and open-circuit voltage (0.09 V). More importantly, the B3S2 monolayer shows a very high theoretical capacity of 1658 mA h g-1 as an anode material for sodium-ion batteries, which is comparable to other similar or common 2D materials. All of these intriguing properties make the B3S2 monolayer a promising 2D anode material for sodium-ion batteries.


A review of cervical spine injury associated with maxillofacial trauma at a UK tertiary referral centre.
The aim of this study was to determine the incidence and patterns of cervical spine injury (CSI) associated with maxillofacial fractures at a UK trauma centre. A retrospective analysis was conducted of 714 maxillofacial fracture patients presenting to a single trauma centre between 2006 and 2012. Of the 714 maxillofacial fracture patients, 2.2% had associated CSI including a fracture, cord contusion or disc herniation. In comparison, 1.0% of patients without maxillofacial trauma sustained a CSI (odds ratio: 2.2, p=0.01). The majority (88%) of CSI cases of were caused by a road traffic accident (RTA) with the remainder due to falls. While 8.8% of RTA related maxillofacial trauma patients sustained a CSI, only 2.0% of fall related patients did (p=0.03, not significant). Most (70%) of the CSIs occurred at C1/C2 or C6/C7 levels. Overall, 455, 220 and 39 patients suffered non-mandibular, isolated mandibular and mixed mandibular/non-mandibular fractures respectively. Their respective incidences of CSI were 1.5%, 1.8% and 12.8% (p=0.005, significant). Twelve patients with concomitant CSI had their maxillofacial fractures treated within twenty-four hours and all were treated within four days. The presence of maxillofacial trauma mandates exclusion and prompt management of cervical spine injury, particularly in RTA and trauma cases involving combined facial fracture patterns. This approach will facilitate management of maxillofacial fractures within an optimum time period.


Androgen signaling connects short isoform production to breakpoint formation at Ewing sarcoma breakpoint region 1.
Ewing sarcoma breakpoint region 1 (EWSR1) encodes a multifunctional protein that can cooperate with the transcription factor ERG to promote prostate cancer. The EWSR1 gene is also commonly involved in oncogenic gene rearrangements in Ewing sarcoma. Despite the cancer relevance of EWSR1, its regulation is poorly understood. Here we find that in prostate cancer, androgen signaling upregulates a 5' EWSR1 isoform by promoting usage of an intronic polyadenylation site. This isoform encodes a cytoplasmic protein that can strongly promote cell migration and clonogenic growth. Deletion of an Androgen Receptor (AR) binding site near the 5' EWSR1 polyadenylation site abolished androgen-dependent upregulation. This polyadenylation site is also near the Ewing sarcoma breakpoint hotspot, and androgen signaling promoted R-loop and breakpoint formation. RNase H overexpression reduced breakage and 5' EWSR1 isoform expression suggesting an R-loop dependent mechanism. These data suggest that androgen signaling can promote R-loops internal to the EWSR1 gene leading to either early transcription termination, or breakpoint formation.


Nomogram model for predicting the risk of post-stroke depression based on clinical characteristics and DNA methylation.
To construct a comprehensive nomogram model for predicting the risk of post-stroke depression (PSD) by using clinical data that are easily collected in the early stages, and the level of DNA methylation, so as to help doctors and patients prevent the occurrence of PSD as soon as possible. We continuously recruited 226 patients with a history of acute ischemic stroke and followed up for three months. Socio-demographic indicators, vascular-risk factors, and clinical data were collected at admission, and the outcome of depression was evaluated at the third month after stroke. At the same time, a DNA-methylation-related sequencing test was performed on the fasting peripheral blood of the hospitalized patients which was taken the morning after admission. A total of 206 samples were randomly divided into training dataset and validation set according to the ratio of 7:3. We screened 24 potentially-predictive factors by Univariate logistic regression and least absolute shrinkage and selection operator (LASSO) regression analysis, and 10 of the factors were found to have predictive ability in the training set. The PSD nomogram model was established based on seven significant variables in multivariate logistic regression. The consistency statistic (C-index) was as high as 0.937, and the area under curve (AUC) in the ROC analysis was 0.933. Replication analysis results in the validation set suggest the C-index was 0.953 and AUC was 0.926. This shows that the model has excellent calibration and differentiating abilities. Gender, Rankin score, history of hyperlipidemia, time from onset to hospitalization, location of stroke, National Institutes of Health Stroke scale (NIHSS) score, and the methylation level of the cg02550950 site are all related to the occurrence of PSD. Using this information, we developed a prediction model based on methylation characteristics.


Metagenomic insights into the microbiota involved in lactate and butyrate production and manipulating their synthesis in alfalfa silage.
Lactate and butyrate are important indicators of silage quality. However, the microorganisms and mechanisms responsible for lactate and butyrate production in silage are not well documented. whole-metagenomic sequencing was used to analyse metabolic pathways, microbiota composition, functional genes, and their contributions to lactate and butyrate production in alfalfa silage with (SA) and without (CK) sucrose addition. Carbon metabolism was the most abundant metabolic pathway. We identified 11 and 2 functional genes associated with lactate and butyrate metabolism, respectively. Among them, D-lactate dehydrogenase (ldhA) and L-lactate dehydrogenase (ldhB) were most important for the transition between D/L-lactate and pyruvate and were primarily related to Lactobacillus in the SA group. The genes encoding L-lactate dehydrogenase (lldD), which decomposes lactate, were the most abundant and primarily associated with Enterobacter cloacae. Butyrate-related genes, mainly encoding butyryl-CoA: acetate CoA-transferase (but), were predominantly associated with Klebsiella oxytoca and Escherichia coli in the CK group. Enterobacteriaceae and Lactobacillaceae were mainly responsible for butyrate and lactate formation, respectively.


Lifetime olfactory memory in the cricket Gryllus bimaculatus.
The time span of olfactory memory retention in the cricket Gryllus bimaculatus was studied. Third- or fourth-instar nymph crickets were trained to associate one odor with water and another odor with saline solution. At 6 weeks and 10 weeks after training, adult crickets exhibited significantly greater preferences for the odor associated with water over that associated with saline solution. The learned preference was altered when they were given reversal training at 6 weeks after training. We conclude that crickets are capable of retaining olfactory memory practically for their lifetime and of easily rewriting it in accordance with experience.


Development of consensus fluorogenically labeled probes of the immunoglobulin heavy-chain gene for detecting minimal residual disease in B-cell non-Hodgkin lymphomas.
We have examined 72 patients with B-cell non-Hodgkin lymphoma (B-NHL) in order to search for consensus sequences of the immunoglobulin heavy chain (IgH) gene, and developed consensus fluorogenically labeled probes for use in an allele-specific oligonucleotide (ASO) real-time quantitative polymerase chain reaction (RQ-PCR) assay of minimal residual disease (MRD). We detected a clonal IgH variable region (VH) sequence in 51 (70.8%) of the 72 B-NHLs, the most frequent VH gene usages being VH3 and VH4 (45/51, 88.2%). It was possible to design three consensus fluorogenic probes for the VH3 gene and one for the VH4 gene avoiding these hypermutations. Our sequencing results suggested that consensus fluorogenic probes would be best based on the 5'-side of the framework region 3 (FR3) because the frequency of somatic hypermutations was significantly lower in the regions on which the probes were based than in the remaining parts of FR3 (P < 0.05). Nineteen (54.3%) of 35 B-NHLs with the VH3 gene and 5 (50%) of 10 with the VH4 gene had sequences identical to at least one of these probes. We found that probes containing one base substitution were still applicable for a MRD study, whereas those containing two or more were not. Therefore, our four probes were applicable for 37 (82.2%) of the 45 patients with VH3 or VH4. This limited number of probes makes a large-scale study of MRD in B-NHL more feasible.


Detection of poststroke oropharyngeal dysphagia with swallowing screening by ultrasonography.
There are currently no standard evaluation tools for poststroke neurogenic oropharyngeal dysphagia. We previously suggested calculating the relative movements of the hyoid bone and larynx by ultrasonography to evaluate swallowing movement. Swallowing movement is altered in neurogenic oropharyngeal dysphagia. Therefore, the present study aimed to verify whether an ultrasonographic evaluation of swallowing movement facilitates the detection of neurogenic oropharyngeal dysphagia. Eighteen healthy male elderly participants (the healthy group) and 18 male stroke patients diagnosed with neurogenic oropharyngeal dysphagia (the dysphagia group) were enrolled. Participants swallowed 5 mL of liquid and water with an adjusted viscosity and the movements of the hyoid bone and larynx were visualized by ultrasonography. The results obtained revealed significant differences in laryngeal duration (static phase), laryngeal displacement (elevation phase), and the hyoid bone-laryngeal motion ratio (HL motion ratio) between the two groups. A multiple regression analysis was performed to adjust for confounding factors, and laryngeal duration (static phase) and the HL motion ratios were identified as factors affecting dysphagia. In the receiver operation characteristic curve of the two variations, the area under the curve for laryngeal duration (static phase) was 0.744 and the cut-off was 0.26 sec with 72.2% sensitivity and 88.9% specificity; the area under the curve for the HL motion ratio was 0.951 and the cut-off was 0.56 with 88.9% sensitivity and 88.9% specificity. Therefore, the objective evaluation of hyoid bone and larynx movements during swallowing by ultrasonography facilitated the detection of neurogenic oropharyngeal dysphagia.


[Value and limits of shoulder ultrasonography].
A report is given on our experiences with approximate 500 soft tissue sonographies of the shoulder. Since about 2 years, all clinically not defineable shoulder pain conditions are submitted to a sonographic examination. We employ a 7.5 MHz linear sonoemitter. The method of examination includes a static and dynamic technique of examination as well as a comparison of the contralateral side. All structures are visualised in two planes and documented on magnetic tape. In view of the intraoperative situs, we want to demonstrate, first, the possibility of a misinterpretation of the preoperative sonographic findings, second, the limits of this method of examination.


Genome-wide DNA methylation profiles in both precancerous conditions and clear cell renal cell carcinomas are correlated with malignant potential and patient outcome.
To clarify genome-wide DNA methylation profiles during multistage renal carcinogenesis, bacterial artificial chromosome array-based methylated CpG island amplification (BAMCA) was performed. Non-cancerous renal cortex tissue obtained from patients with clear cell renal cell carcinomas (RCCs) (N) was at the precancerous stage where DNA hypomethylation and DNA hypermethylation on multiple bacterial artificial chromosome (BAC) clones were observed. By unsupervised hierarchical clustering analysis based on BAMCA data for their N, 51 patients with clear cell RCCs were clustered into two subclasses, Clusters A(N) (n = 46) and B(N) (n = 5). Clinicopathologically aggressive clear cell RCCs were accumulated in Cluster B(N), and the overall survival rate of patients in Cluster B(N) was significantly lower than that of patients in Cluster A(N). By unsupervised hierarchical clustering analysis based on BAMCA data for their RCCs, 51 patients were clustered into two subclasses, Clusters A(T) (n = 43) and B(T) (n = 8). Clinicopathologically aggressive clear cell RCCs were accumulated in Cluster B(T), and the overall survival rate of patients in Cluster B(T) was significantly lower than that of patients in Cluster A(T). Multivariate analysis revealed that belonging to Cluster B(T) was an independent predictor of recurrence. Cluster B(N) was completely included in Cluster B(T), and the majority of the BAC clones that significantly discriminated Cluster B(N) from Cluster A(N) also discriminated Cluster B(T) from Cluster A(T). In individual patients, DNA methylation status in N was basically inherited by the corresponding clear cell RCC. DNA methylation alterations in the precancerous stage may generate more malignant clear cell RCCs and determine patient outcome.


Assessment of patient health literacy: a national survey of plastic surgeons.
Health literacy affects patient participation, compliance, and outcomes. Nearly half of American adults have inadequate functional health literacy. Identification and accommodation of patients with low literacy is an important goal of the American Medical Association, U.S. Department of Health and Human Services, and the Healthy People 2020 initiative. This study aims to assess plastic surgeons' perception of patient literacy. A survey was distributed to American Society of Plastic Surgeons members about time devoted to patient counseling, use of techniques for evaluating and enhancing patient understanding, perception of level of education, and estimated literacy. Participation was voluntary and data were collected anonymously using an online survey tool. There were 235 participants in the survey (9.9 percent response rate). Patient literacy was most frequently assessed using their general impression (62.2 percent) and by asking patients about their employment (37.3 percent); 26.2 percent did not assess literacy. The majority of surgeons (62 percent) reported spending at least 20 minutes counseling new patients, and 37 percent reported spending more than 30 minutes. Lay terminology (94 percent) and pictures/diagrams (84.6 percent) were common patient education aids, whereas only 8.1 percent use teach-back methods. Plastic surgeons overestimated the level of education and reading level of their patients compared with national data. Formal assessment of health literacy is rarely performed, as most plastic surgeons use a general impression. Although plastic surgeons devote significant time to patient counseling, evidence-based communication methods, such as the teach-back method, are underused. Simple, directed questions can identify patients with low literacy skills, to accommodate their communication needs.


Crossing the Rubicon: Behaviorism, Language, and Evolutionary Continuity.
Euan Macphail's work and ideas captured a pivotal time in the late 20th century when behavioral laws were considered to apply equally across vertebrates, implying equal intelligence, but it was also a time when behaviorism was challenged by the view that language was unique to humans, and bestowed a superior mental status. Subsequent work suggests greater continuity between humans and their forebears, challenging the Chomskyan assumption that language evolved in a single step ("the great leap forward") in humans. Language is now understood to be based on an amalgam of cognitive functions, including mental time travel, theory of mind, and what may be more broadly defined as imagination. These functions probably evolved gradually in hominin evolution and are present in varying degrees in non-human species. The blending of language into cognition provides for both interspecies differences in mental function, and continuity between humans and other species. What does seem to be special to humans is the ability to communicate the contents of imagination, although even this is not absolute, and is perhaps less adaptive than we like to think.


Incorporation and degradation of GM1 ganglioside and asialoGM1 ganglioside in cultured fibroblasts from normal individuals and patients with beta-galactosidase deficiency.
The uptake and degradation of GM1 ganglioside (GM1) and asialoGM1 ganglioside (GA1) were studied in cultured fibroblasts from normal individuals and patients with beta-galactosidase deficiency, using the lipid-loading test. The glycolipids were incorporated from the media into the fibroblasts and the terminal galactose was hydrolyzed in normal cells. The hydrolysis rates of GA1 were 80-86% of normal on the 3rd day after loading, while GM1 was hydrolyzed slowly; 35-54% on the 14th day. In infantile GM1 gangliosidosis and I-cell disease, little GM1 and GA1 was hydrolyzed on any day of culture, while fibroblasts from patients with adult GM1 gangliosidosis, Morquio disease type B and galactosialidosis hydrolyzed the lipids at nearly normal rates. The intracellular accumulation of the glycolipids, on the basis of protein content, was abnormally high in the case of infantile GM1 gangliosidosis and I-cell disease, but normal in the other disorders examined. These observations indicate that the in situ metabolism of GM1 and GA1 is probably normal in fibroblasts from patients with adult GM1 gangliosidosis, Morquio disease type B and galactosialidosis, although in vitro beta-galactosidase activities in these disorders are very low. The results are compatible with findings that GM1 and GA1 do not accumulate in the somatic organs of patients with adult GM1 gangliosidosis and galactosialidosis. In I-cell disease, however, the results of the loading test did not agree with the finding that there is little accumulation of glycolipids in postmortem tissues.


Training and accreditation for the treatment of sexual disorders.
The field of "sex therapy" is not defined by specific, limited techniques. Rather, it encompasses a subspecialty based on an understanding of psychodynamics and psychological development but requiring additional skills from other branches of medicine. Despite its breadth and complexity, sex therapy training is unregulated, with the public lacking the protection afforded by standardized training programs or certification. The author outlines the scope of sex therapy as a psychiatric and medical subspecialty and delineates the necessary clinical skills for the physician-practitioner.


[Genetic Characteristics of Echovirus Type 6 Isolated from Hunan Province, China, 2009-2014].
We wished to understand the genetic characteristics of enteric cytopathic human orphan (ECHO) virus type 6 (ECHO6) circulating in China. First, the partial VP1 coding region of six strains of the ECH-O6 virus isolated from cases of hand, foot and mouth diseases during routine surveillance in Hunan Province (China) from 2009 to 2014 were sequenced. Those sequences were analyzed along with 138 sequences of ECHO viruses covering five provinces of China and countries outside China retrieved from the GenBank database. A phylogenetic tree based on partial VPI was constructed, and it indicated that Chinese strains of the ECHO virus could form two distinct evolutionary branches: branch 1 and branch 2. All isolates of the ECHO virus from Hunan Province belonged to the 2c subranch, which revealed that they may share a common evolutionary origin. ECHO strains in branch 2 may be the predominant strains in China due to their wide geographic distribution and long period of circulation. We used nucleotide differences of >30%o as the basis of cluster division. ECHO, viruses could be divided into four clusters (A-D). Cluster D could be divided further into ten subclusters on the basis of nucleotide differences of 15%-30%. All ECHO6 isolates from Hunan Province belonged to the D7 subcluster. These data showed that the ECHO6 strains that circulated in Hunan Province in 2009-2014 were closely related to each other, and probably shared a common evolutionary origin. In addition, at least four distinct lineages of ECHO viruses have circulated in China.


Experimental characterization of the nanoparticle size effect on the mechanical stability of nanoparticle-based coatings.
We present an experimental investigation of the mechanical stability of silica nanoparticle-based coatings as a function of the size of the nanoparticles. The coatings are built following a layer-by-layer procedure, alternating positive and negative surface charges. The mechanical stability of the multilayers is studied in water, on the basis of an ultrasonic cavitation test. The resistance of the coating to cavitation is found to remarkably increase with decreasing the size of the nanoparticles, indicating an increase of the cohesive energy density. The relative contribution of van der Waals and electrical double-layer interactions to the stability of the multilayer is discussed toward their size dependence.


Phase II study of accelerated fractionation radiation therapy with carboplatin followed by PCV chemotherapy for the treatment of anaplastic gliomas.
To conduct a Phase II one-arm study to evaluate the long-term efficacy and safety of accelerated fractionated radiotherapy combined with i.v. carboplatin for patients with previously untreated anaplastic gliomas. Between 1988 and 1992, 90 patients received 1.9-2.0-Gy radiation 3 times a day with 2-h infusions of 33 g/m(2) carboplatin for two 5-day cycles separated by 2 weeks. After radiotherapy, patients received procarbazine, lomustine (CCNU), and vincristine (PCV) for 1 year or until the tumor progressed. Ninety patients were evaluable for analysis. Histologically, 69 had anaplastic astrocytoma; 14, anaplastic oligoastrocytoma; and 7, anaplastic oligodendroglioma. Gross total resection was performed in 20 (22%), subtotal resection in 45 (50%), and biopsy in 25 (28%); reoperation (total or subtotal resection) was performed in 50 (56%) patients. A multivariate analysis showed that a younger age (p = 0.026), Karnofsky performance score (KPS; p = 0.009), and brain necrosis (p = 0.0002) were predictive of a better survival. Results from analysis of extent of surgery (biopsy, subtotal resection, gross total resection) approached significance (p = 0.058). Radiation dose, irradiated tumor volume, and techniques used (boost and fields) were not significant variables. The median survival (MS) of all anaplastic glioma patients was 28.1 months; for anaplastic astrocytoma patients, MS was 28.7 months and 40.8 months for the combined anaplastic oligodendroglioma/oligoastrocytoma patients. Long-term survival occurred in 25% of anaplastic glioma patients who were alive 8.6 years after treatment was initiated. Treatment-induced necrosis was documented by surgery or autopsy in 19 (21%) patients; 21 (23%) had a mixed pattern of necrosis and tumor; and an additional 13 (14%) patients who did not have surgical or autopsy demonstration of predominant radiation necrosis had magnetic resonance imaging (MRI) evidence of radiation necrosis. Serious clinical neurologic deterioration and/or dementia requiring full-time caregiver attention were observed in 9 (10%) patients. When comparable selection criteria are applied, the rate of MS in this study is inferior to results attainable with current radiation and chemotherapy approaches, although the rates of long-term survival are comparable. Theoretically, patients failing therapy and dying earlier than anticipated may be because of excessive central nervous system (CNS) toxicity resulting from the combination of accelerated fractionated irradiation, intensive carboplatin chemotherapy before each radiation fraction, and postirradiation PCV chemotherapy. On the other hand, patients with treatment-induced necrosis survived significantly longer than patients who did not demonstrate MRI or histologic evidence of necrosis (MS, 106 months vs. 18-33 months).


Pathology of the oropharyngeal cavity in six strains of rats: predisposition of Fischer 344 rats for inflammatory and degenerative changes.
The sagittolongitudinal histopathological evaluation of the oropharyngeal cavity in 6 strains of rats revealed a clear predisposition of the Fischer 344 strain for degenerative and inflammatory lesions in this region. A degeneration and calcification predominantly of the laryngeal cartilage is evident in 72%, granulomas of the seromucinous glands in 38%, and an inflammation with bacterial colonies or plant material in the basal part of the laryngotracheal junction in 26% of the Fischer 344 rats. The incidences of these types of lesions were negligible in the other rat strains evaluated. The comparison of control Fischer 344 rats from 2 carcinogenicity studies (untreated group; gavaged group with water, pH 10; gavaged group with propylene glycol/methocel) showed an influence of the gavage technique with the solvent on the survival rate in the female Fischer 344 rats. The lower survival rate was accompanied by the occurrence of food impaction in the oropharyngeal cavity. This increased mortality in female Fischer 344 rats was also associated with a degeneration of the laryngeal cartilages, whereas the formation of granulomas and inflammation seemed to have no direct relationship to the mortality. The gavage technique with the applied solvent was an enhancing factor in the female Fischer 344 rats on mortality, on cartilage degeneration, but not on inflammatory changes. In contrast to the females, male Fischer 344 rats had a higher incidence of granulomas and inflammation, which, however, did not influence the survival rate. In conclusion, Fischer 344 rats, especially the female sex, exposed to chronic daily irritation by gavage, are predisposed to have a high mortality rate in chronic toxicologic tests. An explanation lies in the disposition of the Fischer 344 rat to a high incidence of cartilage degeneration, which presumably leads to a dysfunction of the larynx.


Conflict in the workplace: social workers as victims and perpetrators.
Conflict and violence in the workplace have emerged as a real but inadequately explored concern in the social work profession. The present study surveyed a national random sample of 1029 NASW members about their experiences with client violence and with physical and psychological assault in relationship to practice setting, age, gender, and experience. Although results cannot be generalized due to response bias in the sample, 62 percent of social workers in the study reported they had been victims of physical or psychological assault and 14 percent reported they had committed such an assault on a client within the past year. Most incidents were psychological in nature (primarily verbal aggression), although physical violence was also documented. Male social workers were more likely to be both victims and perpetrators of aggression, and these conflicts were more common in inpatient, correctional, and school settings. Training implications are discussed.


Length dependence of electron transport through molecular wires--a first principles perspective.
One-dimensional wires constitute a fundamental building block in nanoscale electronics. However, truly one-dimensional metallic wires do not exist due to Peierls distortion. Molecular wires come close to being stable one-dimensional wires, but are typically semiconductors, with charge transport occurring via tunneling or thermally-activated hopping. In this review, we discuss electron transport through molecular wires, from a theoretical, quantum mechanical perspective based on first principles. We focus specifically on the off-resonant tunneling regime, applicable to shorter molecular wires (<∼4-5 nm) where quantum mechanics dictates electron transport. Here, conductance decays exponentially with the wire length, with an exponential decay constant, beta, that is independent of temperature. Different levels of first principles theory are discussed, starting with the computational workhorse - density functional theory (DFT), and moving on to many-electron GW methods as well as GW-inspired DFT + Sigma calculations. These different levels of theory are applied in two major computational frameworks - complex band structure (CBS) calculations to estimate the tunneling decay constant, beta, and Landauer-Buttiker transport calculations that consider explicitly the effects of contact geometry, and compute the transmission spectra directly. In general, for the same level of theory, the Landauer-Buttiker calculations give more quantitative values of beta than the CBS calculations. However, the CBS calculations have a long history and are particularly useful for quick estimates of beta. Comparing different levels of theory, it is clear that GW and DFT + Sigma calculations give significantly improved agreement with experiment compared to DFT, especially for the conductance values. Quantitative agreement can also be obtained for the Seebeck coefficient - another independent probe of electron transport. This excellent agreement provides confirmative evidence of off-resonant tunneling in the systems under investigation. Calculations show that the tunneling decay constant beta is a robust quantity that does not depend on details of the contact geometry, provided that the same contact geometry is used for all molecular lengths considered. However, because conductance is sensitive to contact geometry, values of beta obtained by considering conductance values where the contact geometry is changing with the molecular junction length can be quite different. Experimentally measured values of beta in general compare well with beta obtained using DFT + Sigma and GW transport calculations, while discrepancies can be attributed to changes in the experimental contact geometries with molecular length. This review also summarizes experimental and theoretical efforts towards finding perfect molecular wires with high conductance and small beta values.


Will optogenetics be used to treat chronic pain patients?
Chronic pain affects a third of the population and current treatments produce limited relief and severe side effects. An alternative strategy to decrease pain would be to directly modulate somatosensory pathways using optogenetics. Optogenetics involves the use of genetically encoded and optically active proteins, namely opsins, to control neuronal circuits. In preclinical animal models, optical silencing of peripheral nociceptors has been shown to alleviate both inflammatory and neuropathic pain. An opsin-based gene therapy to treat chronic pain patients is not ready yet, but encouraging advances have been made in optical and viral technology. In view of the increasing burden of chronic pain in our aging society, innovative analgesic approaches based on optogenetics are definitely worth exploring.


Maturity of gray matter structures and white matter connectomes, and their relationship with psychiatric symptoms in youth.
Brain predicted age difference, or BrainPAD, compares chronological age to an age estimate derived by applying machine learning (ML) to MRI brain data. BrainPAD studies in youth have been relatively limited, often using only a single MRI modality or a single ML algorithm. Here, we use multimodal MRI with a stacked ensemble ML approach that iteratively applies several ML algorithms (AutoML). Eligible participants in the Healthy Brain Network (N = 489) were split into training and test sets. Morphometry estimates, white matter connectomes, or both were entered into AutoML to develop BrainPAD models. The best model was then applied to a held-out evaluation dataset, and associations with psychometrics were estimated. Models using morphometry and connectomes together had a mean absolute error of 1.18 years, outperforming models using a single MRI modality. Lower BrainPAD values were associated with more symptoms on the CBCL (pcorr = .012) and lower functioning on the Children's Global Assessment Scale (pcorr = .012). Higher BrainPAD values were associated with better performance on the Flanker task (pcorr = .008). Brain age prediction was more accurate using ComBat-harmonized brain data (MAE = 0.26). Associations with psychometric measures remained consistent after ComBat harmonization, though only the association with CGAS reached statistical significance in the reduced sample. Our findings suggest that BrainPAD scores derived from unharmonized multimodal MRI data using an ensemble ML approach may offer a clinically relevant indicator of psychiatric and cognitive functioning in youth.


Insulin glargine versus sitagliptin in insulin-naive patients with type 2 diabetes mellitus uncontrolled on metformin (EASIE): a multicentre, randomised open-label trial.
In people with type 2 diabetes, a dipeptidyl peptidase-4 (DPP-4) inhibitor is one choice as second-line treatment after metformin, with basal insulin recommended as an alternative. We aimed to compare the efficacy, tolerability, and safety of insulin glargine and sitagliptin, a DPP-4 inhibitor, in patients whose disease was uncontrolled with metformin. In this comparative, parallel, randomised, open-label trial, metformin-treated people aged 35-70 years with glycated haemoglobin A(1c) (HbA(1c)) of 7-11%, diagnosis of type 2 diabetes for at least 6 months, and body-mass index of 25-45 kg/m(2) were recruited from 17 countries. Participants were randomly assigned (1:1) to 24-week treatment with insulin glargine (titrated from an initial subcutaneous dose of 0·2 units per kg bodyweight to attain fasting plasma glucose of 4·0-5·5 mmol/L) or sitagliptin (oral dose of 100 mg daily). Randomisation (via a central interactive voice response system) was by random sequence generation and was stratified by centre. Patients and investigators were not masked to treatment assignment. The primary outcome was change in HbA(1c) from baseline to study end. Efficacy analysis included all randomly assigned participants who had received at least one dose of study drug and had at least one on-treatment assessment of any primary or secondary efficacy variable. This trial is registered at ClinicalTrials.gov, NCT00751114. 732 people were screened and 515 were randomly assigned to insulin glargine (n=250) or sitagliptin (n=265). At study end, adjusted mean reduction in HbA(1c) was greater for patients on insulin glargine (n=227; -1·72%, SE 0·06) than for those on sitagliptin (n=253; -1·13%, SE 0·06) with a mean difference of -0·59% (95% CI -0·77 to -0·42, p<0·0001). The estimated rate of all symptomatic hypoglycaemic episodes was greater with insulin glargine than with sitagliptin (4·21 [SE 0·54] vs 0·50 [SE 0·09] events per patient-year; p<0·0001). Severe hypoglycaemia occurred in only three (1%) patients on insulin glargine and one (<1%) on sitagliptin. 15 (6%) of patients on insulin glargine versus eight (3%) on sitagliptin had at least one serious treatment-emergent adverse event. Our results support the option of addition of basal insulin in patients with type 2 diabetes inadequately controlled by metformin. Long-term benefits might be expected from the achievement of optimum glycaemic control early in the course of the disease. Sanofi.


Effect of Environmental Conditions on the Degradation of Florasulam in Typical Soils of Northern China.
The widespread use of florasulam in China makes residues from this herbicide in soil a serious concern due to their potential to pollute the soil environment and groundwater. Accelerating the degradation of these residues will reduce their pollution potential. In this study, we investigated the degradation and adsorption of florasulam in four typical soils in northern China and examined the degradation of florasulam in Inceptisols at different temperatures, soil moisture contents, and pH values, as well as the influence of microorganisms and the use of organic matter and biogas slurry as soil amendments. The half-lives of florasulam in the four soils were 13.6 d (Ultisols), 13.9 d (Vertisols), 15.1 d (Alfisols), and 19.3 d (Inceptisols), and the adsorption ability of the four soils followed the order Inceptisols > Alfisols > Vertisols > Ultisols. Florasulam degradation rates increased as temperature and soil moisture increased and as soil pH decreased (from 8.0 to 6.0). Adding a small amount of organic matter to the soil increased the florasulam degradation rates. The use of biogas slurry also increased the degradation rates. Florasulam half-life in unsterilized soil ( = 19.3 d) was significantly shorter than in sterilized soil ( = 113.4 d). These results provide agricultural producers and environmental managers useful information for reducing the environmental risk associated with florasulam use.


Mindfulness-Based Cognitive Therapy for Unmedicated Obsessive-Compulsive Disorder: A Randomized Controlled Trial With 6-Month Follow-Up.
Background: This was the first randomized controlled trial (RCT) designed to compare the efficacy of mindfulness-based cognitive therapy (MBCT) on unmedicated obsessive-compulsive disorder with that of the first-line treatment for OCD (SSRIs) or a placebo, as well as to analyze the treatment acceptability and safety of MBCT. Methods: A total of 123 unmedicated OCD patients with mild to moderate symptoms were randomly assigned into selective serotonin reuptake inhibitors group (SSRIs group), MBCT group or psycho-education group (PE group), respectively. They were intervened for 10 weeks. The Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) grade was the primary outcome, and Hamilton Depression Scale-24 (HAMD-24) and Hamilton Anxiety Scale (HAMA) grades were secondary outcomes to be measured at baseline, mid-intervention, post-intervention and 14, 22, and 34 weeks of follow-up. The Five Facet Mindfulness Questionnaire (FFMQ) and Sheehan Disability Scale (SDS) were used to assess mindfulness and social functions, respectively. In addition, treatment acceptability (dropout rate and frequency of occurrence) and safety [adverse event (AE)] of MBCT were investigated. Results: Significant differences were detected in the treatment responses among SSRIs group, MBCT group and PE group. Notably, treatment responses were significantly better in the former two groups than that of PE group (χ2 = 6.448, p = 0.04), although we did not identify significant differences between SSRIs group and MBCT group (χ2 = 1.220, p = 0.543). Observed until 6 months of follow-up, there were no significant differences in treatment response among three groups. No AE was recorded in MBCT group. Conclusion: MBCT is effective in the treatment of unmedicated OCD with mild to moderate symptoms comparable to that of SSRIs, which contributes to maintain the treatment outcomes at follow-up. Besides, MBCT is safe with a good clinical compliance.


Cross-cultural Adaptation of the Oral Anticoagulation Knowledge Test to the Brazilian Portuguese.
Patients' knowledge about oral anticoagulant therapy may favor the achievement of therapeutic results and the prevention of adverse pharmacotherapy-related events. Brazil lacks validated instruments for assessing the patient's knowledge about treatment with warfarin. This study aimed to perform the cross-cultural adaptation of the Oral Anticoagulation Knowledge (OAK) Test instrument from English into Portuguese. This is a methodological study developed in an anticoagulation clinic of a public university hospital. The study included initial translation, synthesis of translations, back-translation, review by the experts committee and pre-testing with 30 individuals. We obtained semantic equivalence through the analysis of the referential and general meaning of each item. The conceptual equivalence of the items sought to demonstrate the relevance and acceptability of the instrument. The process of cross-cultural adaptation produced the final version of the OAK Test in Brazilian Portuguese entitled "Teste de Conhecimento sobre Anticoagulação Oral". There was a suitable semantic and conceptual equivalence between the adapted version and the original version, as well as an excellent acceptability of this instrument.


Kinetic study of pH effects on biological hydrogen production by a mixed culture.
The effect of pH on anaerobic hydrogen production was investigated under various pH conditions ranging from pH 3 to 10. When the modified Gompertz equation was applied to the statistical analysis of the experimental data, the hydrogen production potential and specific hydrogen production rate at pH 5 were 1,182 ml and 112.5 ml/g biomass-h, respectively. In this experiment, the maximum theoretical hydrogen conversion ratio was 22.56%. The Haldane equation model was used to find the optimum pH for hydrogen production and the maximum specific hydrogen production rate. The optimum pH predicted by this model is 5.5 and the maximum specific hydrogen production rate is 119.6 ml/g VSS-h. These data fit well with the experimental data (r2=0.98).


Release of cytokines in stored whole blood and red cell concentrate: Effect of leukoreduction.
Storage time of blood components plays a major role in the accumulation of cytokines causing adverse transfusion reactions. The aim was to study the trend in the levels of interleukin-6 (IL-6), IL-8, tumor necrosis factor-alpha (TNF-α) and regulated upon activation, normal T-cells expressed and secreted (RANTES) during storage of whole blood (WB) and red cell concentrate (RCC) and to study the effect of leukoreduction (LR). WB sample was taken on 0, 7, 14, 21, and between 28 and 35 days and plasma aliquots were frozen. Samples from RCC and buffy-coat depleted RCC prepared using Optipress II were collected on 0, 7, 14, 21 and between 28 and 35 days. Cytokine estimation was done using ELISA development kits. Normal range of cytokines was established using 0 day samples of WB. Statistical analysis was done using nonparametric tests. The normal range of IL-6 was 0-23 pg/ml, IL-8 0-12 pg/ml, TNF-α 0-3 pg/ml, and RANTES 1200-2000 pg/ml. IL-6 was in normal range and showed a decreasing trend during storage. IL-8 levels increased significantly from 0 to 35 days. In RCC, the highest level was 480 pg/ml on 28(th) day. It was in the normal range in buffy-coat depleted RCC up to 28 days. RANTES level was significantly low in buffy-coat depleted RCC compared to RCC. We conclude that WB has high levels of IL-8 and RANTES. The levels of cytokines are affected by storage period and LR. Comparison of WB and buffy-coat depleted RCC shows significantly low levels of IL-6, IL-8, and RANTES in buffy-coat depleted RCC. This study emphasizes the use of red cell components instead of WB and buffy-coat depleted RCC instead of RCC.


Outbreak of CTX-M-15-producing Enterobacter cloacae associated with therapeutic beds and syphons in an intensive care unit.
An outbreak of extended-spectrum β-lactamase-producing Enterobacter cloacae (ESBL-ECL) occurred in our intensive care unit (ICU) and involved 18 patients (8 infected and 10 colonized). The mean age of patients was 69 years, and all infected patients had underlying medical conditions. Within hours' recognition of the spread of ESBL-ECL, the infection control team requested for staff education, reinforcement of infection control measures, and environmental screening. New transmissions were observed in the institution after weeks of enhanced infection control measures. Microbial swabbing revealed bacterial contamination of some mattresses and syphons with epidemiologic links between environmental, screening, and clinical isolates. This outbreak resulted in the temporary closure of the ICU for complete biocleaning.


Comprehensive Analysis of Metabolic Genes in Breast Cancer Based on Multi-Omics Data.
Background: Reprogramming of cell metabolism is one of the most important hallmarks of breast cancer. This study aimed to comprehensively analyze metabolic genes in the initiation, progression, and prognosis of breast cancer. Materials and Methods: Data from The Cancer Genome Atlas (TCGA) in breast cancer were downloaded including RNA-seq, copy number variation, mutation, and DNA methylation. A gene co-expression network was constructed by the weighted correlation network analysis (WGCNA) package in R. Association of metabolic genes with tumor-related immune cells and clinical parameters were also investigated. Results: We summarized 3,620 metabolic genes and observed mutations in 2,964 genes, of which the most frequently mutated were PIK3CA (51%), TNN (26%), and KMT2C (15%). Four genes (AKT1, ERBB2, KMT2C, and USP34) were associated with survival of breast cancer. Significant association was detected in the tumor mutation burden (TMB) of metabolic genes with T stage (p = 0.045) and N stage (p = 0.004). Copy number variations were significantly associated with recurrence and prognosis of breast cancer. The co-expression network for differentially expressed metabolic genes by WGCNA suggested that the modules were associated with glycerophospholipid, arachidonic acid, carbon, glycolysis/gluconeogenesis, and pyrimidine/purine metabolism. Glycerophospholipid metabolism correlated with most of the immune cells, while arachidonic acid metabolism demonstrated a significant correlation with endothelial cells. Methylation and miRNA jointly regulated 14 metabolic genes while mutation and methylation jointly regulated PIK3R1. Conclusion: Based on multi-omics data of somatic mutation, copy number variation, mRNA expression, miRNA expression, and DNA methylation, we identified a series of differentially expressed metabolic genes. Metabolic genes are associated with tumor-related immune cells and clinical parameters, which might be therapy targets in future clinical application.


Klebsiella oxytoca outbreak at the Ethio-Swedish Children's Hospital (ESCH).
Klebsiella oxytoca outbreak at the Ethio-Swedish Children's Hospital, is described. The organism was isolated for the first time on Oct. 1992 at the emergency room and subsequently spread to all wards including the neonatal unit of the hospital. The isolates were resistant to Ampicillin, Amoxicillin, Chloramphenicol, Co-trimoxazole and Gentamicin, but sensitive to Amikacin and ceftriaxone. Eighty six percent (182) of the isolates were from blood specimen. Nine out of ten suspected intravenous infusion bags were positive for Klebsiella oxytoca. The source of this nosocomial infection and possible control measures are discussed.


A practical synthesis of trans-3-substituted proline derivatives through 1,4-addition.
A practical four-step synthesis of 3-alkyl-, vinyl-, and aryl-substituted proline derivatives, which are important building blocks for conformationally restrained peptide analogs, was developed. The method relies on a Cu-catalyzed 1,4-addition of Grignard reagents to N-protected 2,3-dehydroproline esters, efficiently prepared in a new one-pot protocol. The 1,4-addition products are obtained with good trans-selectivity (dr 5:1 to 25:1). A nonracemic sample of N-Cbz-3-vinylproline (74% ee) was obtained using Evans oxazolidinone as a chiral auxiliary.


Differential neuronal activity in segments of globus pallidus in Parkinson's disease patients.
Microelectrode trajectories through the globus pallidus of 6 Parkinson's disease (PD) patients yielded neurophysiological 'landmarks' which enabled the identification of neurones located in the external segment (GPe) and internal segments, exterior (GPi,e) and interior (GPi,i) of globus pallidus and the surrounding borders (Bor). Firing rate histograms and inter-spike interval time histograms were constructed for neurones in each region. The neuronal activity in GPi,i was higher than in the other segments, and a high degree of bursting was found in GPe and GPi neurones. This profile of neuronal activity is similar to that observed in monkeys treated with MPTP, suggesting that the observed level of activity of neurones in GPi,i is excessive, and contributes to the bradykinesia and rigidity of PD patients.


Prophylactic Percutaneous Kyphoplasty Treatment for Nonfractured Vertebral Bodies in Thoracolumbar for Osteoporotic Patients.
The occurrence of new vertebral compression fractures (VCFs) is a common complication after percutaneous kyphoplasty (PKP). Secondary VCFs after PKP occur predominantly in the thoracolumbar segment (T11 to L2). Prophylactic injections of cement into vertebral bodies in order to reduce new VCFs have rarely been reported. The main purpose of this study was to investigate whether prophylactically injecting cement into a nonfractured vertebral body at the thoracolumbar level (T11-L2) could reduce the occurrence of new VCFs. From July 2011 to July 2018, PKP was performed in 86 consecutive patients with osteoporotic vertebral compression fractures (OVCFs) in the thoracolumbar region (T11-L2). All patients selected underwent PKP because of existing OVCFs (nonprophylactic group). Additionally, 78 consecutive patients with fractured vertebrae in the thoracolumbar region (T11-L2) with OVCFs underwent PKP and received prophylactic injections of cement into their nonfractured vertebrae in the thoracolumbar region (T11-L2) (prophylactic group). The visual analog scale (VAS) scores and incidence of new VCFs after PKP were compared between the two groups. The mean VAS scores improved from 8.00 ± 0.79 preoperatively to 1.62 ± 0.56 at the last follow-up in the nonprophylactic group and improved from 8.17 ± 0.84 to 1.76 ± 0.34 in the prophylactic group (P > 0.05). In the nonprophylactic group, 21 of 86 patients (24.4%) developed new VCFs within one year after PKP, of whom 15 patients (71.4%) developed VCFs within 3 months. In the prophylactic group, 8 of 78 patients (10.3%) developed new VCFs within one year, and 6 of these 8 patients (75%) developed new VCFs within 3 months. The incidence of new VCFs was significantly higher in the nonprophylactic group than that in the prophylactic group at one year (P = 0.018), but there were no statistically significant differences at three months (P = 0.847). Prophylactic injections of cement into nonfractured (T11-L2) vertebral bodies reduced the incidence of secondary VCFs after PKP in patients with OVCFs, but there was no significant difference in local back pain (VAS) scores between the two groups.


Redondovirus Diversity and Evolution on Global, Individual, and Molecular Scales.
Redondoviridae is a newly established family of circular Rep-encoding single-stranded (CRESS) DNA viruses found in the human ororespiratory tract. Redondoviruses were previously found in ∼15% of respiratory specimens from U.S. urban subjects; levels were elevated in individuals with periodontitis or critical illness. Here, we report higher redondovirus prevalence in saliva samples: four rural African populations showed 61 to 82% prevalence, and an urban U.S. population showed 32% prevalence. Longitudinal, limiting-dilution single-genome sequencing revealed diverse strains of both redondovirus species (Brisavirus and Vientovirus) in single individuals, persistence over time, and evidence of intergenomic recombination. Computational analysis of viral genomes identified a recombination hot spot associated with a conserved potential DNA stem-loop structure. To assess the possible role of this site in recombination, we carried out in vitro studies which showed that this potential stem-loop was cleaved by the virus-encoded Rep protein. In addition, in reconstructed reactions, a Rep-DNA covalent intermediate was shown to mediate DNA strand transfer at this site. Thus, redondoviruses are highly prevalent in humans, found in individuals on multiple continents, heterogeneous even within individuals and encode a Rep protein implicated in facilitating recombination. IMPORTANCERedondoviridae is a recently established family of DNA viruses predominantly found in the human respiratory tract and associated with multiple clinical conditions. In this study, we found high redondovirus prevalence in saliva from urban North American individuals and nonindustrialized African populations in Botswana, Cameroon, Ethiopia, and Tanzania. Individuals on both continents harbored both known redondovirus species. Global prevalence of both species suggests that redondoviruses have long been associated with humans but have remained undetected until recently due to their divergent genomes. By sequencing single redondovirus genomes in longitudinally sampled humans, we found that redondoviruses persisted over time within subjects and likely evolve by recombination. The Rep protein encoded by redondoviruses catalyzes multiple reactions in vitro, consistent with a role in mediating DNA replication and recombination. In summary, we identify high redondovirus prevalence in humans across multiple continents, longitudinal heterogeneity and persistence, and potential mechanisms of redondovirus evolution by recombination.


Stem cell factor improves the repopulating ability of primitive hematopoietic stem cells after sublethal irradiation (and, to a lesser extent) after bone marrow transplantation in mice.
Bone marrow transplantation (BMT) and sublethal irradiation (XRT) cause profound long-term damage to hematopoietic stem cells. We used the competitive repopulation assay in mice to test the ability of granulocyte-macrophage colony-stimulating factor (GM-CSF) and stem cell factor (SCF), cytokines given in clinical settings to enhance marrow recovery after XRT or BMT and to protect the marrow repopulating ability of primitive hematopoietic stem cells (PHSC) after these modalities. The repopulating ability of exhaustible multilineage progenitors (EMP) was also tested after these modalities, with or without cytokines. Repopulating abilities of EMP and PHSC were significantly reduced after XRT or BMT; PHSC were preferentially affected. Administration of SCF to C57B6/J mice after XRT resulted in improved EMP and PHSC repopulating ability, although progenitor numbers--repopulating units--were not completely returned to control levels. Whether given as a single dose or multiple doses, GM after XRT did protect PHSC function from the deleterious effects of XRT, but this was not a significant effect. SCF caused an increase in PHSC repopulating ability after BMT, but this too was not a significant difference. GM after BMT had little effect. SCF administration before XRT led to severe impairment of PHSC function with very little or no stem cell activity observed. Therefore, timing of its administration is an important consideration since preadministration of the cytokine before XRT can be extremely harmful to PHSC function.


Furofuran lignans from a callus culture of Cichorium intybus.
Three new and one known furofuran lignans--syringaresinol derivatives--along with the known phenylpropanoids cichoriin and syringin were isolated from a callus tissue of Cichorium intybus. The compounds were characterised by spectral methods. This is the first report on the presence of furofuran lignans in Cichorium species.


[Prenatal weight loss in the infant (author's transl)].
Hillemanns and coworkers established, that infants born after induced labor were heavier, on the average, than those from a control group; who were born after spontaneous labor. Since it was postulated, that a weight loss preceded the onset of spontaneous labor, the birth weight and length of 444 infants born after induced labor and 70 infants born via a primary cesarean section was compared with a control group of 1,028 uncomplicated births via spontaneous labor. Thirty seven post term infants were also included in the study. The birth weight and length of infants after induced labor or delivered by primary cesarean section significantly higher than those in the control group. The post term infants were also significantly longer, but their weight was not significantly lower, than that in the control group. The major differences could not be accounted for by varying periods of gestation nor could they be accounted for by the special conditions of induced labor or cesarean section. Therefore, the only possibility remaining is that a weight loss precedes spontaneous labor. This may possibly be explained by the reduction in the relative water content which begins before birth and continues through the newborn period or by a relative placenta insufficiency. The infant weight loss and loss of amniotic fluid after the thirtyeighth week of pregnancy refutes the theory, that birth is induced by a stretching of the uterine wall. The possibility is discussed, that the onset of labor is influenced by a corresponding relief from tension such as that, which occurs following a premature rupture of the fetal membranes.


Bilateral Spontaneous Perirenal Hemorrhage due to Initial Presentation of Polyarteritis Nodosa.
Spontaneous perirenal hemorrhage (SPH) is uncommon but can be a life-threatening condition which is associated with flank or abdominal pain and hypovolemia. The etiologies of SPH include tumor, vascular disease, and infection. Among the vascular diseases, polyarteritis nodosa (PAN) is common cause of the SPH. However, patients with PAN usually complain of nonspecific symptoms and the incidence of PAN is relatively rare. So, diagnosis is difficult even though tissue biopsy and angiography help to confirm the PAN. Particularly bilateral perirenal hemorrhage is very rare complication in patients with PAN. We reported a case of bilateral perirenal hemorrhage in the patients with PAN who have continued to take exogenous sex hormone.


On the nature of fur evolution: a phylogenetic approach in Actinobacteria.
An understanding of the evolution of global transcription regulators is essential for comprehending the complex networks of cellular metabolism that have developed among related organisms. The fur gene encodes one of those regulators - the ferric uptake regulator Fur - widely distributed among bacteria and known to regulate different genes committed to varied metabolic pathways. On the other hand, members of the Actinobacteria comprise an ecologically diverse group of bacteria able to inhabit various natural environments, and for which relatively little is currently understood concerning transcriptional regulation. BLAST analyses revealed the presence of more than one fur homologue in most members of the Actinobacteria whose genomes have been fully sequenced. We propose a model to explain the evolutionary history of fur within this well-known bacterial phylum: the postulated scenario includes one duplication event from a primitive regulator, which probably had a broad range of co-factors and DNA-binding sites. This duplication predated the appearance of the last common ancestor of the Actinobacteria, while six other duplications occurred later within specific groups of organisms, particularly in two genera: Frankia and Streptomyces. The resulting paralogues maintained main biochemical properties, but became specialised for regulating specific functions, coordinating different metal ions and binding to unique DNA sequences. The presence of syntenic regions surrounding the different fur orthologues supports the proposed model, as do the evolutionary distances and topology of phylogenetic trees built using both Neighbor-Joining and Maximum-Likelihood methods. The proposed fur evolutionary model, which includes one general duplication and two in-genus duplications followed by divergence and specialization, explains the presence and diversity of fur genes within the Actinobacteria. Although a few rare horizontal gene transfer events have been reported, the model is consistent with the view of gene duplication as a main force of microbial genomes evolution. The parallel study of Fur phylogeny across diverse organisms offers a solid base to guide functional studies and allows the comparison between response mechanisms in relation with the surrounding environment. The survey of regulators among related genomes provides a relevant tool for understanding the evolution of one of the first lines of cellular adaptability, control of DNA transcription.


National Institute of Nutrition: 100 years of empowering the nation through nutrition.
The National Institute of Nutrition (NIN) has reached a remarkable milestone of completing 100 years of exemplary service to the nation. The long journey that started in a humble one-room laboratory at Coonoor (now in Tamil Nadu) in 1918 to a colossus of the nutrition research in the country today is dotted with several interesting vignettes. The NIN has always been at the forefront of need-based, pragmatic research. Its large-scale community-based interventions have been of great practical value in the nation's fight against malnutrition. The evolution of nutrition as a modern science almost coincides with the growth of the Institute. Being the oldest in the fraternity of institutes under the Indian Council of Medical Research (ICMR), the NIN has grown from strength to strength due to the sheer relevance of its contributions in furthering nutrition science and promoting public health in the country. This article provides a historical overview of the evolution and contributions of ICMR-NIN in the areas of nutrition, food safety, public health and policy.


Significance of the hexose monophosphate shunt in experimentally induced cardiac hypertrophy.
1. In three models of cardiac hypertrophy in rats (aortic constriction, application of a single dose of isoproterenol and daily injections of triiodothyronine) the biosynthesis of myocardial adenine nucleotides was enhanced. 2. In hypertrophying hearts due to aortic constriction and isoproterenol application, the activity of glucose-6-phosphate dehydrogenase and the available pool of 5-phosphoribosyl-1-pyrophosphate were increased indicating a stimulation of the hexose monophosphate shunt. In triiodothyronine-treated animals only the cardiac pool of 5-phosphoribosyl-1-pyrophosphate turned out to be elevated. 3. In all three models of cardiac hypertrophy, the enhancement of myocardial adenine nucleotide biosynthesis was exaggerated by ribose. It thus appears that the 5-phosphoribosyl-1-pyrophosphate pool is the limiting factor for the increase of adenine nucleotide biosynthesis under these conditions. 4. Long-term i.v. infusion of ribose (200 mg/kg/h) in isoproterenol-treated rats prevented the decrease of the cardiac ATP concentration induced by isoproterenol. However, the isoproterenol-induced stimulation of total cardiac protein synthesis was not altered, suggesting that the ATP decline may not be the trigger for stimulating protein synthesis in this model of myocardial hypertrophy.


New techniques for the assessment of regional left ventricular wall motion.
The assessment of regional left ventricular (LV) function has been an important yet unresolved problem since the introduction of echocardiography as a diagnostic tool. Abnormal regional LV wall motion is an early finding in multiple cardiac pathologies and its diagnosis is of critical importance. In the last few years diagnostic procedures based on combined use of existing echocardiographic technologies were geared toward improving the accuracy of detection of baseline and/or induced regional wall motion abnormalities. One of the assumptions is that the combination of reduced LV wall thickening and reduced myocardial velocities can be used to accurately diagnose regional myocardial dysfunction. In this article we will discuss several new techniques for the quantification of regional LV function using Doppler echocardiography.


A study of dermatophytoses in Sana'a, Yemen Republic.
The present study describes the extent and causative agents of dermatophytoses in Sana'a, the capital of Yemen Republic. Out of 1100 patients with various skin diseases, 16.6% were affected with dermatophytoses. Among them, 70% were male and the age group 11-20 years was most susceptible to tinea infections. Tinea corporis was the most common disease, followed by tinea capitis. One hundred and seventy isolates of dermatophytes related to 9 species were identified. Microsporum canis was the most prevalent species, followed by Trichophyton violaceum.


Prognostic and Clinical Value of CD44 and CD133 in Esophageal Cancer: A Systematic Review and Meta-analysis.
Despite the importance of CD44 and CD133 in various cancers, the clinicopathological and prognostic values of these biomarkers in esophageal cancer remain debated. Hence, in this study, we did a meta-analysis to explore the correlation between overexpression of these markers and some clinicopathological features and their influence on the survival of esophageal cancer patients. A search in PubMed and Web of Science (among all articles published up to January 16, 2018) was done using the following keywords: esophageal cancer, CD44, CD133, prominin-1, AC133. Suitable studies, that were selected based on the criteria listed in the Materials and Methods section, were chosen and hazard ratios with 95% confidence intervals were estimated if available. Heterogeneity and sensitivity were also analyzed. Furthermore, publication bias was assessed using funnel plots, Egger, and Begg tests. The study included 1346 patients from 13 related studies. The median rates of marker expressions by immunohistochemistry were 35.7% (30%-76.6%) from 9 studies for CD44 and 31.9% (21%-44.2%) from 5 studies for CD133. The accumulative 5-year overall survival rates of CD44-positive and CD133-positive were 1.59% (1.22-2.06) and 1.27% (0.93-1.73), respectively. Meta-analysis showed that CD44 expression had a significant correlation with 5-year overall survival. CD44 overexpression showed a correlation with some clinicopathological features such as lymph node metastasis, vascular invasion, and recurrence of the disease, while it was not the case for coexpression of CD44 and CD133. In conclusion, CD44 overexpression was associated with a 5-year overall survival rate and thus this biomarker can be a suitable prognostic tool in esophageal cancer.


[Laser in surgery--current status and perspectives].
Laser effects on biological tissue depend on wave-length, power-density (W/cm2) and duration of pulsed radiation. Thermal effects may be used for cutting, coagulation and vaporisation. Non-linear effects such as photoablation or photo-disruption are suitable for non-thermal tissue ablation and shock waves can be induced to destroy concrements. Laser is mostly used in clinical surgery for endoscopic treatment of gastrointestinal bleeding and tumors. Laser angioplasty, arthroscopic laser treatment and laser lithotripsy are not yet widely applicable in clinical practice.


Conventional and alternative treatment approaches for Clostridium difficile infection.
Clostridium difficile-associated disease continues to be one of the leading health concerns worldwide. C. difficile is considered as a causative agent of nosocomial diarrhea that causes serious infection, which may result in death. The incidences of C. difficile infection (CDI) in developed countries have become increasingly high which may be attributed to the emergence of newer epidemic strains, extensive use of antibiotics, and limited alternative therapies. The available treatment options against CDI are expensive and promote resistance. Therefore, there is urgent need for new approaches to meet these challenges. This review discusses the current understanding of CDI, the existing clinical treatment strategies and future potential options as antidifficile agents based on the available published works.


Golgi Reassembly and Stacking Protein (GRASP) Participates in Vesicle-Mediated RNA Export in Cryptococcus Neoformans.
Golgi reassembly and stacking protein (GRASP) is required for polysaccharide secretion and virulence in Cryptococcus neoformans. In fungal species, extracellular vesicles (EVs) participate in the export of polysaccharides, proteins and RNA. In the present work, we investigated if EV-mediated RNA export is functionally connected with GRASP in C. neoformans using a graspΔ mutant. Since GRASP-mediated unconventional secretion involves autophagosome formation in yeast, we included the atg7Δ mutant with defective autophagic mechanisms in our analysis. All fungal strains exported EVs but deletion of GRASP or ATG7 profoundly affected vesicular dimensions. The mRNA content of the graspΔ EVs differed substantially from that of the other two strains. The transcripts associated to the endoplasmic reticulum were highly abundant transcripts in graspΔ EVs. Among non-coding RNAs (ncRNAs), tRNA fragments were the most abundant in both mutant EVs but graspΔ EVs alone concentrated 22 exclusive sequences. In general, our results showed that the EV RNA content from atg7Δ and WT were more related than the RNA content of graspΔ, suggesting that GRASP, but not the autophagy regulator Atg7, is involved in the EV export of RNA. This is a previously unknown function for a key regulator of unconventional secretion in eukaryotic cells.


Brain metastases in patients with cancer of unknown primary.
Between January 1985 and December 2000, 916 patients with brain metastases were treated with whole brain radiation therapy (WBRT) at the Department of Radiotherapy, University Hospital Freiburg. In 47 patients, a primary tumor could not be identified (cancer of unknown primary (CUP)). Sixteen patients had a solitary brain metastasis, 31 patients presented with multiple brain metastases. Surgical resection was performed in 15 patients, biopsy alone in 12 patients. WBRT was applied with daily fractions of 2 or 3 Gy to a total dose of 50 or 30 Gy, respectively. According to the recursive partitioning analysis (RPA) classes of the Radiation Therapy Oncology Group for patients with brain metastases none of the patients met the criteria for Class I, 23 for Class II, and 24 for Class III. The median overall survival (OS) for all patients with brain metastases (n = 916) was 3.4 and 4.8 months for patients with CUP (p = 0.45). In patients with CUP (n = 47) the median OS for patients with a single brain metastasis was 7.3 versus 3.9 months for patients with multiple brain metastases (p = 0.05). Median OS for patients with a Karnofsky performance status (KPS) > or = 70 was 6.3 months versus 3.2 months for KPS < 70 (p = 0.01). At multivariate analysis performance status and resection status could be identified as independent prognostic factors for the OS.


Management of the patient and family with neurofibromatosis 2: a consensus conference statement.
A consensus conference on neurofibromatosis 2 (NF2) was held in 2002 at the request of the United Kingdom (UK) Neurofibromatosis Association, with particular emphasis on vestibular schwannoma (VS) surgery. NF2 patients should be managed at specialty treatment centres, whose staff has extensive experience with the disease. All NF2 patients and their families should have access to genetic testing because presymptomatic diagnosis improves the clinical management of the disease. Some clinical manifestations of NF2, such as ocular abnormalities, can be detected in infancy; therefore, clinical screening for at-risk members of NF2 families can start at birth, with the first magnetic resonance (MRI) scan at 10-12 years of age. Minimal interference, maintenance of quality of life, and conservation of function or auditory rehabilitation are the cornerstones of NF2 management, and the decision points to achieve these goals for patients with different clinical presentations are discussed.


(3H)morphine localization in myenteric plexus.
Preferential binding of 3H-labeled morphine to satellite cells, but not to large neurons in the myenteric plexus, is demonstrated autoradiographically. Microfluorometric spectra of the plexus show nerve fibers that contain norepinephrine and impinge on satellite cells. Cells containing serotonin occur occasionally on longitudinal muscle outside the myenteric plexus.


Anaerobic animals from an ancient, anoxic ecological niche.
Tiny marine animals that complete their life cycle in the total absence of light and oxygen are reported by Roberto Danovaro and colleagues in this issue of BMC Biology. These fascinating animals are new members of the phylum Loricifera and possess mitochondria that in electron micrographs look very much like hydrogenosomes, the H2-producing mitochondria found among several unicellular eukaryotic lineages. The discovery of metazoan life in a permanently anoxic and sulphidic environment provides a glimpse of what a good part of Earth's past ecology might have been like in 'Canfield oceans', before the rise of deep marine oxygen levels and the appearance of the first large animals in the fossil record roughly 550-600 million years ago. The findings underscore the evolutionary significance of anaerobic deep sea environments and the anaerobic lifestyle among mitochondrion-bearing cells. They also testify that a fuller understanding of eukaryotic and metazoan evolution will come from the study of modern anoxic and hypoxic habitats.


Biomarkers in sarcoidosis.
Numerous biomarkers have been evaluated for the diagnosis, assessment of disease activity, prognosis, and response to treatment in sarcoidosis. In this report, we discuss the clinical and research utility of several biomarkers used to evaluate sarcoidosis. Areas covered: The sarcoidosis biomarkers discussed include serologic tests, imaging studies, identification of inflammatory cells and genetic analyses. Literature was obtained from medical databases including PubMed and Web of Science. Expert commentary: Most of the biomarkers examined in sarcoidosis are not adequately specific or sensitive to be used in isolation to make clinical decisions. However, several sarcoidosis biomarkers have an important role in the clinical management of sarcoidosis when they are coupled with clinical data including the results of other biomarkers.


Temporal bone histopathology in CHARGE association.
Three temporal bones obtained at autopsy from 2 patients with CHARGE association (Coloboma, congenital Heart disease, Atresia of choanae, mental Retardation and/or central nervous system anomalies, Genital hypoplasia, and Ear anomalies) were examined histopathologically. Both temporal bones from 1 patient showed multiple anomalies in the middle ear, inner ear, and facial nerve. However, the temporal bone obtained from the other patient showed almost normal structures in the inner ear, middle ear, and eustachian tube. These results are different from those of 2 previous reports of temporal bone histopathology regarding CHARGE association. This difference suggests that CHARGE association may arise not from one etiopathogenetic factor, but from complex factors. Special attention to dehiscent facial canal and perilymphatic gusher during otologic surgery in patients with CHARGE association is discussed.


Platelet dysfunction in malaria.
Platelet function tests including platelet aggregation, PF3, bleeding time and clot retraction were studied in 48 malarial patients. The suppression of platelet aggregation was demonstrated in both P. vivax and P. falciparum infection. However, this abnormality was more prominent in malarial patients who had systemic complications and bleeding. The recovery of the impaired platelet aggregation was observed at period of 7 and 14 days after parasitemia in malarial patients without and with systemic complications. The correlation between the suppression of platelet aggregation and thrombocytopenia was observed. From this study, bleeding in malaria are operated by two mechanisms: thrombocytopenia and severely depressed platelet aggregation.


Catalytic, asymmetric, "interrupted" Feist-Bénary reactions.
Pyrimidine derivatives of the cinchona alkaloids function as excellent asymmetric catalysts for the "Interrupted" Feist-Bénary Reaction. This reaction produces highly substituted hydroxydihydrofurans from simple starting materials under mild conditions. The asymmetric reaction gives high enantioselectivities with unsubstituted bromoketones, and high enantio- and diastereoselectivities with substituted substrates. Mechanistic experiments suggest that the hydrobromide salt of the alkaloid derivative is the active catalyst for the reaction.


A quantitative study of thalamocortical and other synapses involving the apical dendrites of corticothalamic projection cells in mouse SmI cortex.
Lesion-induced degeneration was combined with the retrograde transport of horseradish peroxidase (HRP) to examine the thalamocortical and other synaptical relationships of corticothalamic projection cells in mouse SmI cortex. Injections containing 40% HRP were placed in the ventrobasal thalamus and the next day, electrolytic lesions were made of the injection site. About four days later, the animals were perfused with aldehydes and SmI cortex ipsilateral to the injection and lesion sites was tissue chopped and reacted for HRP. The somata of HRP-filled corticothalamic cells in SmI cortex had diameters of about 10 micrometers and occurred in the upper half of layer VI and in the lower half of layer V; their apical dendrites usually terminated within or just below layer IV, but in some instances, extended nearly to the pial surface. Reconstructions of serial thin sections through the layer IV portions of the apical dendrites of seven well-labelled corticothalamic cells showed them to form 7 to 20% of their synapses with degenerating thalamocortical axon terminals. In contrast, the proportion of thalamocortical synapses formed by the layer IV dendrites of corticostriatal (Hersch & White, in preparation) and corticocortical (White & Hersch, 1981) projection cells ranges from 0.3 to 0.9% and from 1.5 to 6.8%, respectively. We interpret these findings to indicate that pyramidal cell dendrites are specified to form characteristic proportions of thalamocortical synapses.


Case Report: Fatigue and Bleeding in a Polymedicated Patient Using Several Herbal Supplementations, Detected with g-Nomic® Software.
This was a case report of severe fatigue and bleeding in a 65-year-old man with ischemic heart disease who was wearing a stent and taking multiple medications for hypertension and diabetes. The use of a drug interaction and personalized prescription software (g-Nomic®) revealed potential interactions, involving acetylsalicylic acid and several non-pharmaceutical products including ginger, blueberry extracts, pineapple juice, docosahexaenoic acid and liquorice. Correction of these interactions resulted in complete remission of the reported side effects. This supports the idea that non-pharmaceuticals potentiated the effects of acetylsalicylic acid on haemostasis, producing the bleeding that would have caused fatigue. It is important to use appropriate tools to detect drug interactions that also take into account commonly used non-pharmaceutical products. Drug interactions can be considered illnesses by themselves.


31P and 13C NMR studies of oxygen transfer during catalysis by 3-deoxy-D-manno-octulosonate cytidylyltransferase from Escherichia coli.
[18O]3-Deoxy-D-manno-octulosonate (KDO), labeled at the anomeric oxygen, was prepared by exchange with [18O]H2O and used to follow the route of oxygen transfer during cytidine 5'-monophosphate-3-deoxy-D-manno-octulosonate (CMP-KDO) formation catalyzed by 3-deoxy-D-manno-octulosonate cytidylyl-transferase (CMP-KDO synthetase). The 31P-NMR signal of the phosphoryl group of CMP-KDO (-5.85 ppm), which appeared as a single resonance when CMP-KDO formation took place with unenriched KDO, appeared as two peaks when CMP-KDO formation took place in the presence of a mixture of [16O]-and [18O]KDO. These results demonstrate the retention of 18O during CMP-KDO formation. Confirmation that the labeled oxygen in CMP-KDO was retained in the "bridge" position between CMP and KDO came from 13C-NMR studies of CMP-KDO formed in the presence of 90% [2-13C, 18O] KDO. The prominent C-2 KDO resonance in CMP-KDO, which is normally a doublet at 101.4 ppm (Kohlbrenner, W.E., and Fesik, S.W. (1985) J. Biol. Chem. 260, 14695-14700), appeared as four peaks when a mixture of [2-13C,16O]- and [2-13C, 18O]KDO was used, confirming the direct bonding of 18O to the C-2 of KDO in CMP-KDO. These results are consistent with a nucleophilic displacement mechanism for CMP-KDO formation.


Investigation of hemophagocytic lymphohistiocytosis in severe sepsis patients.
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition characterized by uncontrolled inflammation and has common clinical and laboratory features with sepsis. The aim of this study was to investigate patients treated with severe sepsis who had bicytopenia for the presence of HLH. Patients with severe sepsis who were non-responsive to treatment and developed at least bicytopenia were included. Peripheral blood samples were collected and stored for later evaluation for natural killer (NK) activity and soluble interleukin-2 receptor levels. Diagnostic criteria of HLH were retrospectively analyzed. Seventy-five of 382 patients (20%) were followed as severe sepsis and septic shock. Among them, 40 patients had bicytopenia. Twenty-six of 40 patients were excluded due to the presence of active solid or hematological malignancies. Three patients died before fulfillment of HLH criteria and one patient denied to give consent. All of the remaining 10 patients had at least five of the eight criteria according to criteria of the Histiocyte Society. Only one of 10 patients was diagnosed as HLH and received treatment during intensive care unit stay. None of the 10 patients survived. This study emphasizes to consider the possibility of HLH and the need of rapid assessment of patients with severe sepsis who had bicytopenia and were resistant to treatment in intensive care.


[Exosomal biomarkers for kidney disease.]
Development of minimally invasive biomarkers is necessary for early detection, prognosis prediction, severity assessment and treatment monitoring in different kidney diseases. Recently, many studies have been conducted worldwide on marker proteins and micro RNA(miRNA)contained in urinary extracellular vesicles(EVs)including exosomes. This article reviews urinary EV-contained biomarkers, including proximal tubular endocytic receptor megalin, for kidney diseases such as diabetic nephropathy.