Fulminant Wegener's granulomatosis: a case report.
Granulomatosis Wegener is anti-neutrophil cytoplasmic antibodies (ANCAs)-associated systemic vasculitis of unknown etiology. It is manifested as granulomatous necrotizing inflammation of the upper and lower parts of the respiratory tract, glomerulonephritis and systemic vasculitis involving most frequently the skin and oral mucous membrane. Sera markers of this disease are c-ANCA and pANCA. We presented a female patient aged 52 years with purpuric spots that had appeared on the lower legs ten months before admission to our hospital. The disease ran an aggressive course, and a month before admission hemorrhagic bullae, skin ulcers, hoarseness, dyspnea, generalized arthralgia, fatigue and fever had rapidly developed. Histopathological examination of a skin sample revealed necrotizing vasculitis, so that sera markers concentrations were elevated (c-ANCA, p-ANCA). There was a perforation of the nasal septum found on rhinoscopy. During hospitalization acute abdominal pain occurred, a possible tumor in the small intestine and possible granulomas in the liver were seen by multislice computed tomography (MSCT) examination, with normal findings on the lungs and kidneys. The treatment started with methylprednisolone: 500 mg/d i.v. infusion for consecutive 3 days, then 60 mg/d. On exploratory laparotomy small bowel perforation and diffuse peritonitis were found. Unstable in the postoperative period, the patient died on the day 12 of hospitalization. The reported patient was with fulminant Wegener's granulomatosis, dominantly with skin changes and with gastrointestinal manifestation. This case accents the need for rapid systemic clinical evaluation in a severely ill patient with unclear diagnosis.


Anthranoid laxative use is not a risk factor for colorectal neoplasia: results of a prospective case control study.
Anthranoid laxatives are the most commonly used purgatives in the therapy of acute and chronic constipation. Recent experimental data and a prospective cohort study provide evidence of a possible risk of anthranoid use for the development of colorectal neoplasms. We performed a prospective case control study at the University of Erlangen to investigate the risk of anthranoid laxative use for the development of colorectal adenomas or carcinomas. A total of 202 patients with newly diagnosed colorectal carcinomas, 114 patients with adenomatous polyps, and 238 patients (controls) with no colorectal neoplasms who had been referred for total colonoscopy were studied. The use of anthranoid preparations was assessed by standardised interview, and endoscopically visible or microscopic melanosis coli was studied by histopathological examination. There was no statistically significant risk of anthranoid use for the development of colorectal adenomas (unadjusted odds ratio 1.0; 95% CI 0.5-1.9) or carcinomas (unadjusted odds ratio 1.0; 95% CI 0.6-1.8). Even after adjustment for the risk factors age, sex, and blood in the stools by logistic regression analysis the odds ratio for adenomas was 0.84 (95% CI 0. 4-1.7) and for carcinomas 0.93 (95% CI 0.5-1.7). Also, there were no differences between the patient and control groups for duration of intake. Macroscopic and high grade microscopic melanosis coli were not significant risk factors for the development of adenomas or carcinomas. Neither anthranoid laxative use, even in the long term, nor macroscopic or marked microscopic melanosis coli were associated with any significant risk for the development of colorectal adenoma or carcinoma.


Aortic endograft surveillance: use of fast-switch kVp dual-energy computed tomography with virtual noncontrast imaging.
To assess endoleak detection and patients' radiation exposure using fast-switch peak kilovoltage (kVp) dual-energy computed tomography (DECT) with virtual noncontrast (VNC) imaging. Institutional review board approved retrospective review of triphasic CTs for endograft follow-up: single-energy true noncontrast (TNC) and dual-energy arterial- and venous-phase postcontrast scans on GE HD-750 64-detector scanners. Iodine-subtracted VNC images generated from dual-energy data. Two radiologists (VNC readers) independently performed 2 reading sessions without TNC images: (1) arterial and VNC and (2) venous and VNC. Interrater agreement, leak detection sensitivity, and dose estimates were calculated. Original dictations described 24 endoleaks in 78 scans. Virtual noncontrast reader agreement was high (κ = 0.78-0.79). Virtual noncontrast reader ranges for sensitivity and negative predictive value for leak detection were 87.5% to 95.8% and 94.0% to 98.0% in venous phase. Dose reduction estimate was 40% by eliminating one phase and 64% by eliminating 2 phases of imaging. Virtual noncontrast images from fast-switch peak kilovoltage DECT data can substitute for TNC imaging in the postendograft aorta, conferring substantial dose reduction. Eliminating 1 of 2 postcontrast phases further reduces dose, with greater negative predictive value for leak detection in the venous versus the arterial phase. Thus, the use of a monophasic venous-phase DECT with VNC images is suggested for long-term endograft surveillance in stable patients.


Bystander Intervention Behavior as Function of Victimization History, Opportunity, and Situational Context.
Preliminary research has demonstrated the utility of bystander interventions in reducing sexual assault, and initial research has begun extending this type of intervention to intimate partner violence more broadly. However, the extant research is limited by methodological issues that fail to examine opportunity for intervention relative to intervention behaviors as well as a failure to examine intervention rates across differing risk situations. Further, there are many unexplored factors that may impact bystander intervention behavior, notably previous experiences with intimate partner violence and sexual assault. Thus, the current study examined bystander opportunities and intervention across situations of varying risk to the bystander, as well as the relationship of opportunity/intervention relative to victimization history. Given the rates of sexual assault and IPV on college and university campuses, the research examined the number of times college students (N = 393) encountered a range of situations in which bystander intervention may be indicated, and their intervention behavior across varying risk levels to the bystander. Results demonstrated that individuals with a history of psychological victimization were more likely to intervene across all situation types, but sexual and physical victimization provided mixed support for hypotheses. No differences in witnessing or intervening were found as a function of gender. These results replicate previous findings, and further provide evidence for a more nuanced approach to examine bystander behavior intervention. Implications and directions for future research are discussed.


Heteroaggregation between PEI-coated magnetic nanoparticles and algae: effect of particle size on algal harvesting efficiency.
Colloidal interactions between magnetic nanoparticles (NPs) and algal cells are of paramount significance to magnetophoretic separation of algal biomass from water. This study evaluated the size effect of magnetic NPs (MNPs) coated with polyethylenimine (PEI) on the separation efficiency of Scenedesmus dimorphus as well as on the recovery efficiency of MNPs from algal biomass. Results showed that algal harvesting efficiency (HE) increased from ca. 60% to 85% as the diameter of PEI-coated MNPs increased from 9 to 53 nm. Likewise, algal recovery capacity (algae/MNPs, w/w) also showed the same size dependence. But a large size (247 nm) led to a decline of algal HE, which was correctly interpreted by a settling model that predicts large sizes of MNPs could eventually reduce the settling velocity under magnetophoresis. The extended Derjaguin-Landau-Verwey-Overbeek theory revealed that the particle size and PEI coating both influenced the interaction energies (e.g., energy barrier) between MNPs and algae. Particularly, PEI coating significantly reduced the energy barrier between MNPs and algae and thereby increased their heteroaggregation and algal HE. Moreover, PEI-coated MNPs were recovered from the harvested algae biomass through a chemical-free ultrasonic method, and the recovery efficiency appeared to be higher for larger MNPs. Overall, the synthesized sizes of applied MNPs will not only affect algal HE but also have economic implications on magnetophoretic algal separation technologies.


Cyclic AMP-mediated control of meiosis: effects of progesterone, cholera toxin, and membrane-active drugs in Xenopus laevis oocytes.
Progesterone depressed rapidly (50% at 1 min) and persistently cyclic AMP (cAMP) concentration that had been elevated by cholera toxin in Xenopus laevis oocytes. cAMP remained below 1 pmol per oocyte (mean basal level) for approximately 1 hr and thereafter rose to approximately 120% of control values, while germinal vesicle (nucleus) breakdown did not occur. In the absence of cholera toxin, progesterone treatment for 6 hr maintained cAMP concentration below the basal level (but not lower than 80%), and germinal vesicle breakdown occurred. Experiments in the presence of phosphodiesterase inhibitors suggested that progesterone modulates adenylate cyclase activity. The maturation promoting factor, which is formed after 3-5 hr of progesterone treatment and provokes germinal vesicle breakdown after its injection into untreated oocytes, also decreased cAMP concentration, an observation that may explain its "autoamplification." Nonsteroidal inducers of meiosis reinitiation (e.g., propranolol, methoxyverapamil, mersalyl) diminished the cholera toxin-mediated accumulation of cAMP, in contrast to compounds devoid of meiotic-inducing capacity and antagonist to progesterone action, such as gammexane (an inositol analogue) and 5'-deoxy-S-(2-methylpropyl)-5'-thioadenosine (a methylase inhibitor), that increased the nucleotide level. The fine control, suggested by the effects of small changes in cAMP levels, gives evidence of great sensitivity to a critical determinant governing meiotic cell division.


Psychiatric adverse effects of pediatric corticosteroid use.
Corticosteroids, highly effective drugs for myriad disease states, have considerable neuropsychiatric adverse effects that can manifest in cognitive disorders, behavioral changes, and frank psychiatric disease. Recent reviews have summarized these effects in adults, but a comprehensive review on corticosteroid effects in children has not been published since 2005. Here, we systematically review articles published since then that, we find, naturally divide into 3 main areas: (1) chronic effects of acute prenatal and neonatal exposure associated with prematurity and congenital conditions; (2) immediate behavioral effects of acute exposure via oncological protocols; and (3) acute behavioral effects of sporadic use in children and adolescents with other conditions. PsycInfo, MEDLINE, Embase, and Scopus were queried to identify articles reporting psychiatric adverse effects of corticosteroids in pediatric patients. Search terms included corticosteroids, adrenal cortex hormones, steroid psychosis, substance-induced psychoses, glucocorticoids, dexamethasone, hydrocortisone, prednisone, adverse effects, mood disorders, mental disorders, psychosis, psychotic, psychoses, side effect, chemically induced, emotions, affective symptoms, toxicity, behavior, behavioral symptoms, infant, child, adolescent, pediatric, paediatric, neonatal, children, teen, and teenager. Following guidelines for systematic reviews from the Potsdam Consultation on Meta-Analysis, we have found it difficult to draw specific conclusions that are more than general impressions owing to the quality of the available studies. We find a mixed picture with neonates exposed to dexamethasone, with some articles reporting eventual deficits in neuropsychiatric functioning and others reporting no effect. In pediatric patients with acute lymphoblastic leukemia, corticosteroid use appears to correlate with negative psychiatric and behavioral effects. In children treated with corticosteroids for noncancer conditions, adverse effects have been observed both during treatment and after cessation, although the data from article to article are not consistent enough to establish dose relationships. By and large, inhaled corticosteroids are considered safe and free of severe neuropsychiatric effects. Although both antipsychotic medications and benzodiazepines have been used to treat corticosteroid-induced mania and psychosis, no unified management strategy has emerged. Large-scale standardized investigations are needed to clarify the psychiatric effect of corticosteroids on children in all these conditions. Meanwhile, there is general agreement that patients as well as caregivers should be warned of the potential for behavioral adverse effects when patients receive these drugs.


Comparison of ELISA and indirect immunofluorescence in the detection of IgG and IgM antitoxoplasma antibodies.
We have compared ELISA and IFA for the quantitation of IgG and IgM antitoxoplasma antibodies on whole sera and purified IgM fractions. In all the sera examined from adult patients the good correspondence of the two tests is expressed by a correlation coefficient of 0.77 (p = 0.001). However, we have observed that both IgM-ELISA and IgM-IFA performed on whole serum may lead either to false positive results due to presence of rheumatoid factors or to false negative results due to the competition with high level of IgG antibodies. The use of the simplified gel filtration method for separation of IgM fraction allowed the detection of IgM in 40 out of 75 adults patients by IgM IFA and in 39 by the same tests resulted negative if performed on whole serum. The separation of IgM fractions seems a necessary step for detecting IgM antibodies by IgM IFA in 12 of 14 newborns sera with clinical and serological evidence of congenital toxoplasmosis. The conventional IgM ELISA was constantly negative when performed on both whole sera or pure IgM IFA positive fractions of the same newborns.


Donor leukocyte infusions in acute lymphocytic leukemia.
Donor leukocyte infusion (DLI) has well-documented activity in CML but the role of DLI in other diseases is less well defined. To evaluate the strategy in acute lymphocytic leukemia (ALL) we evaluated 44 ALL patients from 27 centers who were treated with DLI. Patients with persistent or recurrent disease received DLI from the original marrow donor (30 matched related, four mismatched family, and 10 matched unrelated). Chemotherapy was given before DLI to 28 patients. Of 15 patients who received no pre-DLI chemotherapy, two achieved complete remissions, lasting 1112 and 764+ days. In four patients who received DLI as consolidation of remission induced by chemotherapy or immunosuppression-withdrawal, duration of remission post DLI was 65, 99, 195 and 672+ days. Of 25 patients who received DLI in the nadir after chemotherapy, 13 survived > or =30 days post DLI but did not achieve remission, seven died within less than 30 days post DLI, and five entered remissions that lasted 42, 68, 83, 90, 193 days. Seven patients who did not respond to the initial DLI received a second DLI; none of these patients attained durable remission. Eighteen of 37 evaluable patients developed acute GVHD and five of 20 evaluable patients developed chronic GVHD. Overall actuarial survival is 13% at 3 years. In conclusion, DLI has limited benefit in ALL. New approaches are needed in this group of patients.


Scales of orientation, directed walks and movement path structure in sharks.
1. Animal search patterns reflect sensory perception ranges combined with memory and knowledge of the surrounding environment. 2. Random walks are used when the locations of resources are unknown, whereas directed walks should be optimal when the location of favourable habitats is known. However, directed walks have been quantified for very few species. 3. We re-analysed tracking data from three shark species to determine whether they were using directed walks, and if so, over which spatial scales. Fractal analysis was used to quantify how movement structure varied with spatial scale and determine whether the sharks were using patches. 4. Tiger sharks performed directed walks at large spatial scales (at least 6-8 km). Thresher sharks also showed directed movement (at scales of 400-1900 m), and adult threshers were able to orient at greater scales than juveniles, which may suggest that learning improves the ability to perform directed walks. Blacktip reef sharks had small home ranges, high site fidelity and showed no evidence of oriented movements at large scales. 5. There were inter- and intraspecific differences in path structure and patch size, although most individuals showed scale-dependent movements. Furthermore, some individuals of each species performed movements similar to a correlated random walk. 6. Sharks can perform directed walks over large spatial scales, with scales of movements reflecting site fidelity and home range size. Understanding when and where directed walks occur is crucial for developing more accurate population-level dispersal models.


The association between Type D personality and the metabolic syndrome: a cross-sectional study in a University-based outpatient lipid clinic.
Type D personality has been associated in the past with increased cardiovascular mortality among patients with established coronary heart disease. Very few studies have investigated the association of type D personality with traditional cardiovascular risk factors. In this study, we assessed the association between type D personality and the metabolic syndrome. New consecutive patients referred to an outpatient lipid clinic for evaluation of possible metabolic syndrome were eligible for inclusion in the study. The metabolic syndrome was defined according to the International Diabetes Federation (IDF) diagnostic criteria. Type D personality was assessed with the DS-14 scale. Multivariate regression techniques were used to investigate the association between personality and metabolic syndromes adjusting for a number of medical and psychiatric confounders. Three hundred and fifty-nine persons were screened of whom 206 met the diagnostic criteria for the metabolic syndrome ("cases") and 153 did not ("control group"). The prevalence of type D personality was significantly higher in the cases as compared to the control group (44% versus 15% respectively, p < 0.001). In multivariate logistic regression analysis the presence of Type D personality was significantly associated with metabolic syndrome independently of other clinical factors, anxiety and depressive symptoms (odds ratio 3.47; 95% Confidence Interval: 1.90 - 6.33). Type D personality was independently associated with the metabolic syndrome in this cross-sectional study. The potential implications of this finding, especially from a clinical or preventive perspective, should be examined in future research.


15-Lipoxygenase and 15-hydroxyeicosatetraenoic acid regulate intravascular thrombosis in pulmonary hypertension.
Pulmonary arterial hypertension (PAH) is a disease characterized by thickening of pulmonary artery walls, elevated pulmonary vascular resistance, pulmonary vascular thrombotic lesions, and right heart failure. Recent studies suggest that 15-lipoxygenase (15-LO)/15-hydroxyeicosatetraenoic acid (15-HETE) play an important role in PAH, acting on arterial walls. Here, we show evidence for the action of the 15-LO/15-HETE signaling in the pulmonary vascular thrombotic lesions in the experimental PAH models. Platelet deposition was augmented in rats exposed to hypoxia and Sugen 5416, which were both prevented by nordihydroguaiaretic acid (NDGA), a 15-LO inhibitor. Chronic hypoxic resulted in the platelet deposition specifically in pulmonary vasculature, which was reversed by 15-LO inhibitor. The 15-LO pathway mediated in the endothelial dysfunction induced by hypoxia in vivo. Meanwhile, 15-HETE positively regulated the generation of IL-6 and monocyte chemoattractant protein-1 (MCP-1). The coagulation and platelet activation induced by hypoxia were reversed by 15-LO inhibitor NDGA or the MCP-1 inhibitor synthesis inhibitor bindarit in rats. The 15-LO/15-HETE signaling promoted the coagulation and platelet activation, which was suppressed by MCP-1 inhibition. These results therefore suggest that 15-LO/15-HETE signaling plays a role in platelet activation and pulmonary vascular thrombosis in PAH, involving MCP-1.


Treatment of corn with lactic acid or hydrochloric acid modulates the rumen and plasma metabolic profiles as well as inflammatory responses in beef steers.
High-grain diets that meet the energy requirements of high-producing ruminants are associated with a high risk of rumen disorders. Mild acid treatment with lactic acid (LA) has been used to modify the degradable characteristics of grains to improve the negative effects of high-grain diets. However, the related studies mainly focused on dairy cows and explored the effects on rumen fermentation, production performance, ruminal pH and so forth. And up to date, no studies have reported the hydrochloric acid (HA) treatment of grains for ruminant animals. Therefore, based on metabolomics analysis, the aim of this study was to evaluate the effects of treatment of corn by steeping in 1% LA or 1% HA for 48 h on the rumen and plasma metabolic profiles in beef steers fed a high corn (48.76%) diet with a 60:40 ratio of concentrate to roughage. The inflammatory responses of beef cattle fed LA- and HA-treated corn were also investigated. Based on ultra-high-performance liquid tandem chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS) metabolomics and multivariate analyses, this study showed that steeping corn in 1% LA or 1% HA modulated the metabolic profiles of the rumen. Feeding beef steers corn steeped in 1% LA or 1% HA was associated with lower relative abundance of carbohydrate metabolites, amino acid metabolites, xanthine, uracil and DL-lactate in the rumen; with higher ruminal pH; with lower concentrations of acetate, iso-butyrate and iso-valerate; and with a tendency for lower ruminal lipopolysaccharide (LPS) concentrations. Moreover, the data showed lower concentrations of plasma C-reactive protein, serum amyloid A, haptoglobin, interleukin (IL)-1β and IL-8 in beef steers fed 1% LA- or HA-treated corn. The 1% LA treatment decreased the concentrations of plasma LPS, LPS-binding protein and tumour necrosis factor-alpha and the relative abundance of L-phenylalanine, DL-3-phenyllactic acid and tyramine in plasma. The 1% HA treatment decreased the relative abundance of urea in plasma and increased the relative abundance of all amino acids in the plasma. These findings indicated that LA or HA treatment of corn modulated the degradation characteristics of starch, which contributed to improving the rumen and plasma metabolic profiles and to decreasing inflammatory responses in beef steers fed a high-concentrate diet.


Stability of citrate, PVP, and PEG coated silver nanoparticles in ecotoxicology media.
Silver nanoparticles (AgNPs) are present in the environment and a number of ecotoxicology studies have shown that AgNPs might be highly toxic. Nevertheless, there are little data on their stability in toxicology media. This is an important issue as such dynamic changes affect exposure dose and the nature of the toxicant studied and have a direct impact on all (eco)toxicology data. In this study, monodisperse citrate, PVP, and PEG coated AgNPs with a core size of approximately 10 nm were synthesized and characterized; their behavior was examined in standard OECD media used for Daphnia sp. acute and chronic tests (in the absence of Daphnia). Surface plasmon resonance, size, aggregation, and shape were monitored over 21 days, comparable to a chronic exposure period. Charge stabilized particles (citrate) were more unstable than sterically stabilized particles. Replacement of chloride in the media (due to concerns over chloride-silver interactions) with either nitrate or sulfate resulted in increased shape and dissolution changes. PVP-stabilized NPs in a 10-fold diluted OECD media (chloride present) were found to be the most stable, with only small losses in total concentration over 21 days, and no shape, aggregation, or dissolution changes observed and are recommended for exposure studies.


Heart and tumors: location, metastasis, clinical manifestations, diagnostic approaches and therapeutic considerations.
Cardiac neoplasms, whether primary or secondary, are more and more easily diagnosed in the present era. For the primary heart tumors, myxomas and sarcomas constitute the most common neoplasms, whereas for the secondary ones, lung cancer constitutes the most common primary location. Cardiac neoplasms may involve the endocardium, the myocardium, the epicardium, the valves or any combination of these. Their clinical manifestations are not specific and depend on their anatomic location and size. Diagnosis of cardiac neoplasms has become more feasible with the use of echocardiography and other imaging techniques (computed tomography and magnetic resonance). The major problem, however, still remains that most diagnoses are late, especially for malignant tumors. For resectable tumors, surgery remains the mainstay of treatment, whereas for metastatic disease palliative treatment remains the only therapeutic option. This paper reviews the types of heart tumors, their clinical symptoms, the diagnostic approaches and the therapeutic tools used by physicians.


[HIV infection in a patient with a referral diagnosis of sore throat].
HIV infection was documented in a patient with hairy leukoplakia and oral candidiasis who had the wrong referral diagnosis of sore throat in the absence of dental complaints. Dental treatment at an infectious hospital led to regression of oral mucosa lesions, but failed to arrest the progress of severe pneumonia presumably caused by a specific pathogen.


Color-dilution alopecia in dogs.
Color-dilution alopecia is a relatively uncommon hereditary skin disease seen in "Blue" and other color-diluted dogs. This syndrome is associated with a color-dilution gene. The initial clinical signs are the gradual onset of a dry, dull and poor hair coat quality. Hair shafts and hair regrowth are poor, and follicular papules may develop and progress to frank comedones. Hair loss and comedo formation are usually most severe on the trunk, especially color-diluted area on the skin. Six cases of color-dilution alopecia are reported in 3 months to 10 years old dogs. The breeds of dogs are blue Doberman Pinscher, Miniature Pinscher, Dachshund, and Schnauzer. Grossly, extensive partial hair loss was seen on the skin. Histopathologically, the epidermis is relatively normal but may be hyperplastic. Hair follicles are characterized by atrophy and distortion. Heavily clumped melanin is present in the epidermis, dermis and hair follicles.


Sostdc1 deficiency accelerates fracture healing by promoting the expansion of periosteal mesenchymal stem cells.
Loss of Sostdc1, a growth factor paralogous to Sost, causes the formation of ectopic incisors, fused molars, abnormal hair follicles, and resistance to kidney disease. Sostdc1 is expressed in the periosteum, a source of osteoblasts, fibroblasts and mesenchymal progenitor cells, which are critically important for fracture repair. Here, we investigated the role of Sostdc1 in bone metabolism and fracture repair. Mice lacking Sostdc1 (Sostdc1(-/-)) had a low bone mass phenotype associated with loss of trabecular bone in both lumbar vertebrae and in the appendicular skeleton. In contrast, Sostdc1(-/-) cortical bone measurements revealed larger bones with higher BMD, suggesting that Sostdc1 exerts differential effects on cortical and trabecular bone. Mid-diaphyseal femoral fractures induced in Sostdc1(-/-) mice showed that the periosteal population normally positive for Sostdc1 rapidly expands during periosteal thickening and these cells migrate into the fracture callus at 3days post fracture. Quantitative analysis of mesenchymal stem cell (MSC) and osteoblast populations determined that MSCs express Sostdc1, and that Sostdc1(-/-) 5day calluses harbor >2-fold more MSCs than fractured wildtype controls. Histologically a fraction of Sostdc1-positive cells also expressed nestin and α-smooth muscle actin, suggesting that Sostdc1 marks a population of osteochondral progenitor cells that actively participate in callus formation and bone repair. Elevated numbers of MSCs in D5 calluses resulted in a larger, more vascularized cartilage callus at day 7, and a more rapid turnover of cartilage with significantly more remodeled bone and a thicker cortical shell at 21days post fracture. These data support accelerated or enhanced bone formation/remodeling of the callus in Sostdc1(-/-) mice, suggesting that Sostdc1 may promote and maintain mesenchymal stem cell quiescence in the periosteum.


Genetic diversity of mastitis-associated Klebsiella pneumoniae in dairy cows.
The objectives of this study were to determine the level of genetic diversity of Klebsiella pneumoniae isolated from clinical mastitis cases and to define genotypes most commonly associated with the disease. Individual quarter milk samples were collected from a single privately owned dairy herd over a 2-yr period and submitted to the Laboratory for Udder Health, Minnesota Veterinary Diagnostic Laboratory, University of Minnesota, for bacteriological culture. Eighty-four K. pneumoniae isolates were obtained and fingerprinted by repetitive DNA sequence PCR, 43 by pulsed-field gel electrophoresis (PFGE), and 29 by multilocus sequence typing (MLST). Significant genetic diversity was observed among the isolates regardless of the fingerprinting method used. Simpson's diversity index was 93.5, 96.1, and 97.0% when analyzed by repetitive DNA sequence PCR (n = 84), pulse field gel electrophoresis (n = 43), and MLST (n = 29), respectively. In some cases more than 1 genotype was obtained from a single milk sample originating from an individual quarter. The majority of infections were observed during the winter and accounted for 69.0% of K. pneumoniae mastitis cases. There was a negative correlation between a matrix of fingerprints similarity and a matrix of temporal distances. The MLST results revealed 5 new and novel allelic types, which have not been previously reported in the MLST database. Three isolates shared MLST types with human clinical isolates, raising the possibility that some K. pneumoniae isolates, of bovine origin, may be capable of causing disease in humans. There were 21 genotypes present within the herd, and there was no evidence for nonrandom distribution of genotypes uniquely associated with mastitis. We have shown, using 3 distinct genotyping methods, that K. pneumoniae isolated from clinical mastitis within a single dairy herd is caused by a genetically diverse population and that multiple genotypes can be isolated from a mastitic quarter. The data suggest that mastitis can be caused by a variety of K. pneumoniae genotypes. Diverse genotypes may have different levels of invasiveness and virulence and may originate from various sources within the dairy.


Dynamic assessment of multilingual children's word learning.
Teachers and clinicians may struggle to provide early identification to support multilingual children's language development. Dynamic assessments are a promising approach to identify and support children's language development. We developed and studied a novel word learning task that is dynamic and language neutral. It makes use of multilingual children's abilities to apply language transfer, fast mapping and socially embedded language to the learning of new words. A total of 26 children attending kindergarten in French participated in this study. Within this group, 13 different home languages were spoken. Children took part in a dynamic assessment task of their word learning that consisted of a test-teach-retest task. Children's scores on this task were compared with their language abilities reported by their parents, amount of language exposure and scores on standardized tests of vocabulary. All tasks were delivered in French. Children had higher accuracy for known words as compared with new words in the task, which may suggest transfer of knowledge from their first language. They also showed increased accuracy in identifying and naming the new words across the three trials, suggesting fast mapping of these new vocabulary items. Finally, the scores on the dynamic task correlated to children's vocabulary scores on the standardized tests, but not parent report of language development, or the amount of exposure to the language of school. This novel dynamic assessment task taps into the process of vocabulary learning, but is less influenced by prior language knowledge. Together, these findings provide insight into early word learning by young multilingual children and proposes a conceptual model for identifying strategies to support second language acquisition. What is already known on the subject Many barriers exist with regards to assessing the language abilities of multilingual children when a clinician aims to assess their language abilities in both languages. An alternative approach is to measure children's language processing abilities. What this paper adds to existing knowledge A novel dynamic and multilingual task was developed and implemented in this study. This task builds on children's word learning abilities that include cross-language transfer, fast-mapping, and socially imbedded learning. This multilingual task was found to tap into vocabulary learning but was not influenced by prior language knowledge. What are the potential or actual clinical implications of this work? Applying a task that focuses on language processing abilities is a promising strategy to capture language abilities in multilingual children. In addition, the dynamic nature of this tasks allows a clinician to identify scaffolding strategies that best support children's word learning.


Neurosurgical practice liability: relative risk by procedure type.
Neurosurgeons have the highest exposure to litigation of all medical and surgical specialties. To determine the relative risk of claims for compensation and indemnity by procedure type. The most common alleged factors and clinical outcomes are also determined. The Physician Insurers Association of America Data Sharing Project was queried for all claims involving a neurosurgeon with an incident date during the calendar year 2006. Data were compared with the American Association of Neurological Surgeons National Neurosurgical Procedural Statistics 2006 Survey. Statistical analysis was performed using the χ test and Fisher exact test as appropriate. Claims were most common after spine surgery, followed by medical management and cranial surgery. Compared with spine surgery, cranial surgery was significantly less likely to result in a claim (P < .0001, relative risk: 0.45). However, the average indemnity for spine surgery was $278,362 vs $423,539 for medical management and $438,183 for cranial surgery. The most common alleged factors in spine surgery were improper performance, wrong level operated on, and unindicated procedure. The most common alleged factors in medical management were errors in diagnosis and failure to monitor a patient. The most common alleged factors in cranial surgery were errors in diagnosis and improper performance. For all claims, the most common clinical outcomes were paraplegia, infection, other unspecified complications, and cauda equina syndrome. Claims are statistically less likely to occur after cranial surgery. However, indemnity is higher in cranial and medical management cases than in spine surgery cases. Nonsurgical treatment is a common source of liability in neurosurgical practice.


Comparison of MED 12 gene mutation and microRNA-124 expression in leiomyoma and myometrium of Turkish patients.
It is believed that there are still unclear areas in the formation mechanism of leiomyomas. In our study, it was aimed to investigate the formation mechanisms of leiomyomas due to local MED 12 gene exon 2 mutation and local microRNA-124 expression in a Turkish population. Thirty patients who underwent hysterectomy for leiomyoma uteri at Gaziantep University between January 2013 and January 2016 were included in our study. In the pathology specimens of these patients, the patient's myometrium tissue and her own leiomyoma tissue were analysed via quantitative Realtime PCR in association with MED 12 exon 2 mutation and microRNA-124 expression. The average age of the 30 patients included in our study is 46.67 ± 5.42 and 13 patients had single leiomyoma; 17 patients had more than one leiomyoma. There were significantly higher c.130G> T (p.G44C) mutation and c.131G> A (p.G44A) mutation of MED 12 gene exon in leiomyoma tissues than healthy myometrium tissues of same patients. There was a 3.7-fold decrease in the expression of microRNA-124 in leiomyoma tissues compared to intact eutopic myometrium tissues, but this difference was not statistically significant. In recent studies, it has been suggested that MED 12 gene may play an active role in the formation of fibroids. MED12 and β-catenin / Wnt pathway were emphasized, and alternative genetic pathways are sought in fibroid formation. Also, tumour suppressor and oncogenesis effects of microRNAs have been demonstrated in many different studies. Since it is involved in the Wnt pathway, microRNA-124 has been blamed by some previous studies for the formation of fibroids. This study demonstrates that MED12 exon 2 mutations and probably microRNA-124 gene expressions might contribute to uterine leiomyoma pathology.


Prognostic value of PUMA expression in patients with HBV-related hepatocellular carcinoma.
The p53 upregulated modulator of apoptosis (PUMA) is a potent apoptosis inducer that is downexpressed in various tumor types. The aim of this study was to explore the prognostic significance of PUMA expression in patients with hepatitis B virus-related hepatocellular carcinoma (HCC). PUMA expressions were examined in 80 pairs of tissues to compare its expression between cancer tissues and paired noncancerous liver tissues using immunohistochemistry (IHC). Relationship between the PUMA expression level and clinicopathological characteristics and clinic outcomes was analyzed. PUMA protein was all positive in paired non-tumor tissue samples. PUMA were downregulated in 61.25% (49/80) of tumor tissues compared with non-tumor tissues. PUMA levels in cancer tissues were significantly lower than non-tumor in patients with recurrence-related factors and patients at higher stage (stage II, III) (p < 0.05). In addition, the expressions level in tumor tissues showed a significant correlation with advanced TNM stage (p = 0.013) and present of recurrence-related factors (p = 0.002). Furthermore, Kaplan-Meier survival analysis revealed that weak PUMA expression was associated with poor 3-year disease-free survival (DFS) and overall survival (OS) in HCC patients. Finally, multivariate analyses identified that PUMA was an independent poor-prognostic predictor for DFS and OS in patients with HBV-related HCC. Our results suggest that PUMA expression is a novel prognostic indicator in HBV-related HCC and may be a potential target for diagnosis and gene therapy.


Reliability of the Kirby-Bauer disc diffusion method for detecting methicillin-resistant strains of Staphylococcus aureus.
The resistance of Staphylococcus aureus to methicillin and related drugs can be reliably determined by using the Kirby-Bauer method of susceptibility testing if the incubation temperature is 35 C or below, but resistance may be missed at 37 C. The 1-mug discs of oxacillin and nafcillin or the 5-mug discs of methicillin may be used for this purpose but not the 1-mug discs of cloxacillin. The latter fail to discriminate between sensitive and resistant staphylococci by zone measurement; some resistant strains of staphylococci may show larger zones of inhibition than sensitive strains. Stability of these antibiotic-containing discs was studied under conditions of temperature and humidity variation that might be encountered in a clinical laboratory refrigerator. Oxacillin discs were the most stable and are to be preferred for susceptibility testing. Nafcillin discs were less stable, and methicillin discs lose their potency rapidly unless carefully stored in a refrigerator with a desiccant.


Selective and sensitive detection of acetylcholinesterase activity using denatured protein-protected gold nanoclusters as a label-free probe.
Based on the fluorescence quenching of novel denatured protein-protected gold nanoclusters, a label-free detection method of acetylcholinesterase (AChE) activity has been developed. Using denatured bovine serum albumin (dBSA), in which 35 cysteine residues can interact polyvalently with Au nanoclusters (AuNCs) as a stabilizing agent, water-soluble and stable fluorescent gold nanoclusters were synthesized. The fluorescence of the AuNCs was quenched by thiocholine that was produced from the AChE hydrolysis of S-acetylthiocholine iodide (ACTI) to detect the AChE activity. The linear range of the method was 0.005-0.15 U mL(-1). The limit of detection (LOD) was 0.02 mU mL(-1). Other enzymes and metal ions, i.e., GPT, γ-GT, GOx, K(+), Ca(2+) and Na(+), showed minimal interference. Using the fluorescence probe, satisfactory results for the detection of the AChE activity in human serum were obtained.


Acute hypertension after nitric oxide synthase inhibition is mediated primarily by increased endothelin vasoconstriction.
To determine the quantitative roles played by the different vasoconstrictor systems in the acute pressor response in conscious rats before and after inhibition of nitric oxide synthase with Nw-nitro-L-arginine methyl ester (L-NAME). In conscious male Sprague-Dawley rats, previously instrumented with aortic and venous catheters, the contributions of the different systems were assessed by maximal cumulative pharmacological blockade of alpha 1-adrenoceptors (1 mg/kg prazosin intraperitoneally), AT1 receptors (30 mg/kg losartan intraperitoneally) and V1/V2 receptors (10 mg/kg [beta-mercapto-beta, beta-cyclopenta-methylenepropionyl1, O-Et-Tyr2-Val4-Arg8]-vasopressin per min intravenously). In addition, the contribution of endothelin-1-induced vasoconstriction in response to 100 mg/kg L-NAME intraperitoneally to the hypertension was assessed by administering 5-100 mg/kg ETA/ETB receptor antagonist PD 145 065 intravenously under three different conditions: as the last step of a series of antagonists in the cumulative pharmacological blockade after having induced the L-NAME pressor response; alone before L-NAME treatment; and alone after the full development of the L-NAME pressor response. A separate group of rats was treated acutely with 30 mg/kg losartan intraperitoneally or pretreated for 3 days with 30 mg/kg angiotensin I converting enzyme inhibitor enalapril via drinking water alone or in combination with 1% salt was used to assess the role of the renin-angiotensin system in the L-NAME-induced hypertension. Short-term administration of the combined ETA/ETB receptor antagonist PD 145065 did not change the arterial pressure under control conditions. Inhibition of the renin-angiotensin system, alpha 1-adrenoceptors or vasopressin receptors alone or in combination did not alter the magnitude of the L-NAME pressor response. In contrast, our results show that both treatments before and during acute nitric oxide synthase blockade hypertension using the ETA/ETB receptor antagonist PD 145065 abolished almost completely (approximately 85%) the pressor response. These studies indicate that the predominant mechanism of hypertension, at least in the acute phase, after acute nitric oxide synthase blockade with L-NAME is associated with a marked increase in ETA/ETB receptor activation rather than with increases in alpha 1, AT1 and V1/V2 receptor activation. It remains to be determined whether endothelin participates also in the chronic phase of nitric oxide-deficient hypertension.


Improved NMDA Receptor Activation by the Secreted Amyloid-Protein Precursor-α in Healthy Aging: A Role for D-Serine?
Impaired activation of the N-methyl-D-aspartate subtype of glutamate receptors (NMDAR) by D-serine is linked to cognitive aging. Whether this deregulation may be used to initiate pharmacological strategies has yet to be considered. To this end, we performed electrophysiological extracellular recordings at CA3/CA1 synapses in hippocampal slices from young and aged mice. We show that 0.1 nM of the soluble N-terminal recombinant fragment of the secreted amyloid-protein precursor-α (sAPPα) added in the bath significantly increased NMDAR activation in aged but not adult mice without impacting basal synaptic transmission. In addition, sAPPα rescued the age-related deficit of theta-burst-induced long-term potentiation. Significant NMDAR improvement occurred in adult mice when sAPPα was raised to 1 nM, and this effect was drastically reduced in transgenic mice deprived of D-serine through genetic deletion of the synthesizing enzyme serine racemase. Altogether, these results emphasize the interest to consider sAPPα treatment targeting D-serine-dependent NMDAR deregulation to alleviate cognitive aging.


Functional Reconstruction of Tracheal Defects by Protein-Loaded, Cell-Seeded, Fibrous Constructs in Rabbits.
Tracheal stenosis is a life-threatening disease and current treatments include surgical reconstruction with autologous rib cartilage and the highly complex slide tracheoplasty surgical technique. We propose using a sustainable implant, composed of a tunable, fibrous scaffold with encapsulated chondrogenic growth factor (transforming growth factor-beta3 [TGF-β3]) or seeded allogeneic rabbit bone marrow mesenchymal stromal cells (BMSCs). In vivo functionality of these constructs was determined by implanting them in induced tracheal defects in rabbits for 6 or 12 weeks. The scaffolds maintained functional airways in a majority of the cases, with the BMSC-seeded group having an improved survival rate and the Scaffold-only group having a higher occurrence of more patent airways as determined by microcomputed tomography. The BMSC group had a greater accumulation of inflammatory cells over the graft, while also exhibiting normal epithelium, subepithelium, and cartilage formation. Overall, it was concluded that a simple, acellular scaffold is a viable option for tracheal tissue engineering, with the intraoperative addition of cells being an optional variation to the scaffolds.


[Severe infection from invasive beta-hemolytic streptococcus group A. Three cases of toxic shock observed in resuscitation].
Group A streptococci (GAS) may cause a variety of infections, some of which are severe and may be life-threatening. Patients affected by severe invasive GAS infections may develop, early in the course of the infection, a syndrome characterized by circulatory insufficiency with multiple organ failure: Streptococcal Toxic Shock-Like syndrome (Strep-TSLS). The presence of shock and organ failure differentiate it from other types of invasive GAS infections. Three cases patients presenting with the Strep-TSLS, over a period of 16 months in our multidisciplinary 10-bed ICU are described. The Strep-TSLS was of nosocomial origin in the first case, due to poststernotomy wound infection, caused from erysipela in the second patient, and associated to a puerperal sepsis in the third case, respectively. In this small series the primary sources of streptococcal infection associated with the syndrome are confirmed to be in soft tissues and skin. One patient died early after the admission to the ICU, whereas the other two patients completely recovered with appropriate antibiotic and supportive treatment although early diagnosis and radical operative debridement may have been conclusive in one case. All 3 observed cases fulfilled the consensus case definition of "certain case of Strep-TSLS", whose criteria have been recently revised.


Multiple functionality in nanotube transistors.
Calculations of quantum transport in a carbon nanotube transistor show that such a device offers unique functionality. It can operate as a ballistic field-effect transistor, with excellent characteristics even when scaled to 10 nm dimensions. At larger gate voltages, channel inversion leads to resonant tunneling through an electrostatically defined nanoscale quantum dot. Thus the transistor becomes a gated resonant-tunneling device, with negative differential resistance at a tunable threshold. For the dimensions considered here, the device operates in the Coulomb blockade regime, even at room temperature.


Effect of grafting materials on osseointegration of dental implants surrounded by circumferential bone defects. An experimental study in the dog.
This study was designed to evaluate the effect of gap width and graft placement on bone healing around implants placed into simulated extraction sockets in the mandibles of four beagle dogs. Four Ti-Unite implants (13 mm x 3.3 mm) were placed on each side of the mandible. Three implants were surrounded by a 1.35 mm circumferential and a 5 mm deep gap around the coronal portion of the implants. A fourth implant was inserted conventionally into both sides of the mandibles as a positive control. The gaps were filled with either Bio-Oss, autogenous bone or with a blood clot alone. The study design was balanced for animal, side and modality. Ground sections were prepared from biopsies taken at 3 months, and computer-aided histometric measurements of bone/implant contact and area of bone within threads were made for the coronal 5 mm. Data were analysed using analysis of variance. The mean bone/implant contact was 9.8 mm for the control and ranged from 9.3 to 11.3 mm for the three test modalities. The corresponding values for area within threads were 1 mm(2) and 1-1.2 mm(2). Modality had a significant effect on both bone/implant contact (F=16.9; P<0.0001) and area within threads (F=16.7; P<0.0001). The results of this study suggest that both autogenous bone graft and Bio-Oss played an important role in the amount of hard tissue fill and osseointegration occurring within marginal bone defects around implants.


Population prevalence of albuminuria in the Australian Diabetes, Obesity, and Lifestyle (AusDiab) study: immunonephelometry compared with high-performance liquid chromatography.
Microalbuminuria is an independent risk factor for cardiovascular morbidity and mortality in the general population. Standard immunochemical urinary albumin assays detect immunoreactive albumin, whereas high-performance liquid chromatography (HPLC) detects both immunoreactive and immunounreactive albumin. Using data from the Australian Diabetes, Obesity, and Lifestyle cohort study of randomly selected community-based Australian adults, spot urine samples were tested for albuminuria (spot urine albumin-creatinine ratio [ACR]: normal, < 30 mg/g; microalbuminuria, 30 to 300 mg/g; and macroalbuminuria, > 300 mg/g) by using both immunonephelometry (IN) and HPLC (n = 10,010). Bland-Altman analysis showed significant bias, with a greater ACR by means of HPLC, particularly at lower levels of ACR. Mean ACR was 15.8 mg/g (95% confidence interval [CI], 12.3 to 19.2) by means of IN compared with 30.0 mg/g (95% CI, 27.0 to 35.0) by means of HPLC. The prevalence of microalbuminuria was 4 times greater by means of HPLC compared with IN (20% versus 5.5%). In all demographic and comorbid subgroups associated with microalbuminuria, the prevalence of microalbuminuria increased by 2 to 4 times. A total of 1,743 subjects (17.4%) classified as normoalbuminuric by means of IN were reclassified as microalbuminuric by means of HPLC. Using multivariate logistic regression, women, patients with untreated and treated hypertension, and those with impaired glucose tolerance or diabetes were associated significantly with a change in category from normoalbuminuric to microalbuminuria by means of HPLC. HPLC measures significantly more urinary albumin within the normoalbuminuria and microalbuminuria range, resulting in a significant increase in prevalence of microalbuminuria. Longitudinal studies are needed to determine whether the extra individuals identified by means of HPLC are at increased risk for developing hard clinical outcomes (renal and cardiovascular).


Remote cerebellar hemorrhage following supratentorial craniotomy.
Cerebellar hemorrhage remote from the site of surgery may complicate neurosurgical procedure. The exact pathophysiology of this type of hemorrhage is poorly understood. We retrospectively compared 16 patients who had remote cerebellar hemorrhage (RCH) with a case-matched control cohort, to determine the significance of perisurgical and surgical factors that may predispose patients to such bleeding events. From 1 June 2005 to 31 December 2008, postoperative routine head computed tomographic (CT) scan was performed in our institution and 16 patients with RCH after supratentorial neurosurgical procedure were identified. The medical charts of these 16 cases and a control cohort of 64 patients were recorded. All parameters were analyzed with regards to various variables. The incidence RCH after supratentorial craniotomy increased after postoperative computed tomographic scan. The mechanism of cerebellar hemorrhage in this series of patients is most likely multifactorial. Several variables showed a significant association with the occurrence of RCH. Multivariate analysis indicated that the following two factors independently correlated with occurrence of RCH: (1) postoperative epidural drainage amount; and (2) history of previous cerebrovascular accident (CVA) with cerebral atrophy. All cases with RCH underwent medical treatment and no neurological sequelae associated with RCH. Postoperative epidural drainage amount and history of previous CVA with cerebral atrophy can reliably predict the occurrence of cerebellar hemorrhage after supratentorial craniotomy. One of the most important strategies to minimize hazardous complications is to be aware of these potential risk factors and to take action to prevent them.


Alterations in Helicobacter pylori outer membrane and outer membrane vesicle-associated lipopolysaccharides under iron-limiting growth conditions.
Outer membrane vesicles (OMVs) shed from the gastroduodenal pathogen Helicobacter pylori have measurable effects on epithelial cell responses. The aim of this study was to determine the effect of iron availability, and its basis, on the extent and nature of lipopolysaccharide (LPS) produced on H. pylori OMVs and their parental bacterial cells. Electrophoretic, immunoblotting and structural analyses revealed that LPSs of bacterial cells grown under iron-limited conditions were notably shorter than those of bacteria and OMVs obtained from iron-replete conditions. Structural analysis and serological probing showed that LPSs of iron-replete cells and OMVs expressed O-chains of Lewis(x) with a terminal Lewis(y) unit, whereas Lewis(y) expression was notably reduced on bacteria and OMVs from iron-limiting conditions. Unlike the O-chain, the core oligosaccharide and lipid A moieties of iron-replete and iron-limited bacteria and their OMVs were similar. Quantitatively, shed OMVs from iron-replete bacteria were found to be LPSenriched, whereas shed OMVs from iron-limited bacteria had a significantly reduced content of LPS. These differences were linked to bacterial ATP levels. Since iron availability affects the extent and nature of LPS expressed by H. pylori, host iron status may contribute to H. pylori pathogenesis.


Adjustment to and satisfaction with retirement: two of a kind?
Multiactor panel data on 778 Dutch employees were used to examine adjustment to and satisfaction with retirement. Regression analyses revealed that adjustment and satisfaction are related, but not identical. Adjustment problems arise from preretirement anxiety about the social consequences of retirement and from a lack of control over the decision. Retirement satisfaction is primarily related to the individual's access to key resources: finances, health, and the marital relationship. The study shows that the retirement transition is multidimensional. The transition involves two developmental challenges: adjustment to the loss of the work role and the social ties of work, and the development of a satisfactory postretirement lifestyle. Making a distinction between these two aspects of the retirement experience is important for a better understanding of the psychological process following retirement.


Endovascular Treatment of Acute Ischemic Stroke Under General Anesthesia: Predictors of Good Outcome.
The choice of anesthetic technique, general anesthesia (GA) versus Monitored Anesthesia Care, may impact the outcome of patients undergoing endovascular treatment of acute ischemic stroke (AIS). The aim of this study was to identify the factors associated with good discharge outcome in patients receiving GA for AIS. Electronic medical records of patients above 18 years old who underwent endovascular treatment of AIS under GA at a Comprehensive Stroke Center from 2010 to 2014 were reviewed. Good outcome was defined as discharge modified Rankin Score 0 to 2 and poor outcome as modified Rankin Score 3 to 6; logistic regression analysis was performed to examine the association between the clinical characteristics and the outcome. In total, 88 patients (56 males), aged 63±15 years with median National Institute of Health Stroke Scale (NIHSS) score 16 (range, 4 to 38) were included. Nineteen (22%) patients had good outcome and 78 (88%) had systolic blood pressure below the guideline recommended 140 mm Hg under GA. After adjusting for age and NIHSS score, the independent predictors of good discharge outcomes were higher maximum end-tidal carbon dioxide (odds ratio [OR], 1.14; confidence interval [CI], 1.02-1.28; P=0.02) and extubation after endovascular treatment (OR, 26.31; CI, 4.80-144.12; P<0.0001). A secondary analysis was performed after excluding 25 patients emergently intubated in the Emergency Department for airway protection. In the logistic regression analysis controlling for age and NIHSS score, postprocedure extubation was still associated with higher odds of good outcomes (OR, 13.35; CI, 2.58-68.90; P=0.002). These findings indicate the importance of ventilation management and extubation after endovascular intervention under GA in patients with AIS.


Chemical synthesis and biochemical reactivity of bacteriophage lambda PR promoter.
By a combination of chemical and enzymatic methods, a 75 base pair DNA duplex containing the sequence of the lambda PR promoter including the OR1 and OR2 cI repressor binding sites was synthesized. The solid support phosphite triester procedure (Caruthers, M. H. et al., Cold Spring Harbor Symposia on Quantitative Biology XLVII, in press) was used for the synthesis of oligonucleotides comprising the sequence. We report here an adaptation of the method of DNA synthesis in test tubes. Assembly of the oligonucleotides involved the use of T4 polynucleotide kinase and T4 DNA ligase. We show that the synthetic DNA is recognized by RNA polymerase and cI repressor in a manner identical to the same control region contained on a restriction fragment isolated from bacteriophage lambda DNA. Our synthetic approach using chemically synthesized promoter variants is thus suitable for studies probing the function of promoters.


Risk Factors for Hospitalization and Effect of Immunosuppression on Clinical Outcomes Among an Urban Cohort of Patients With Mpox.
During the 2022 mpox outbreak most patients were managed as outpatients, but some required hospitalization. Uncontrolled human immunodeficiency virus (HIV) has been identified as a risk factor for severe mpox. Patients with mpox diagnosed or treated within the Johns Hopkins Health System between 1 June and 15 December 2022 were included. The primary outcome of interest was risk of hospitalization. Demographic features, comorbid conditions, treatment, and clinical outcomes were determined. A total of 353 patients were tested or treated for mpox; 100 had mpox diagnosed or treated (median age, 35.3 years; 97.0% male; 57.0% black and 10.0% Hispanic; 46.0% people with HIV [PWH]). Seventeen patients (17.0%) required hospitalization, 10 of whom were PWH. Age >40 years, race, ethnicity, HIV status, insurance status, and body mass index >30 (calculated as weight in kilograms divided by height in meters squared) were not associated with hospitalization. Eight of 9 patients (88.9%) with immunosuppression were hospitalized. Immunosuppression was associated with hospitalization in univariate (odds ratio, 69.3 [95% confidence interval, 7.8-619.7]) and adjusted analysis (adjusted odds ratio, 94.8 [8.5-1060.1]). Two patients (11.8%) who were hospitalized required intensive care unit admission and died; both had uncontrolled HIV infection and CD4 T-cell counts <50/µL. Median cycle threshold values for the first positive mpox virus sample did not differ between those who were hospitalized and those who were not. Immunosuppression was a significant risk factor for hospitalization with mpox. PWH with CD4 T-cell counts <50/µL are at high risk of death due to mpox infection. Patients who are immunosuppressed should be considered for early and aggressive treatment of mpox, given the increased risk of hospitalization.


Multi-state model for predicting ocular progression in acute Stevens-Johnson syndrome/toxic epidermal necrolysis.
This study aimed to clarify the etiologic factors predicting acute ocular progression in SJS/TEN, and identify patients who require immediate and intensive ophthalmological treatment. We previously conducted two Japanese Surveys of SJS/TEN (i.e., cases arising between 2005-2007 and between 2008-2010), and obtained the medical records, including detailed dermatological and ophthalmological findings, of 230 patients. Acute ocular severity was evaluated as none, mild, severe, and very severe. A multi-state model assuming the Markov process based on the Cox proportional hazards model was used to elucidate the specific factors affecting the acute ocular progression. Our findings revealed that of the total 230 patients, 23 (24%) of 97 cases that were mild at initial presentation worsened to severe/very severe. Acute ocular progression developed within 3 weeks from disease onset. Exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) and younger patient age were found to be statistically significant for the progression of ocular severity from mild to severe/very severe [hazard ratio (HR) 3.83; 95% confidence interval (CI) 1.48 to 9.91] and none to severe/very severe [HR 0.98; 95% CI 0.97 to 0.99], respectively. The acute ocular severity score at worst-condition was found to be significantly correlated with ocular sequelae. Thus, our detailed findings on acute ocular progression revealed that in 24% of SJS/TEN cases with ocular involvement, ocular severity progresses even after initiating intensive treatment, and that in younger-age patients with a history of exposure to NSAIDs, very strict attention must be given to their ophthalmological appearances.


Effect of social deprivation on disease severity and outcome in patients with rheumatoid arthritis.
Social deprivation is now recognised to have an important impact on morbidity and mortality. This study sought to ascertain the effect of deprivation, if any, on disease severity, functional disability, and outcome in rheumatoid patients in Glasgow. 814 patients with rheumatoid arthritis (RA) were assessed for clinical, functional, and laboratory indices of disease activity. Deprivation categories for individual patients were determined using the Carstairs index. Five year follow up is available for 440 patients. The study population of RA patients live largely in the most deprived areas. Patients from deprived areas have significantly poorer function at outset and at five years as defined by the Health Assessment Questionnaire (HAQ) score. This is not attributable to differences in disease duration in patients from the most deprived regions or compliance with treatment. Furthermore, these patients do not achieve over five years the initial functional level of those living in the most advantaged localities. RA patients from deprived areas have poorer function, which is associated with greater need--medical, social, and paramedical. Strategies and resources for healthcare need to be adjusted according to this variation.


A 23,000-year record of surface water pH and PCO2 in the western equatorial Pacific Ocean.
The oceans play a major role in defining atmospheric carbon dioxide (CO2) levels, and although the geographical distribution of CO2 uptake and release in the modern ocean is understood, little is known about past distributions. Boron isotope studies of planktonic foraminifera from the western equatorial Pacific show that this area was a strong source of CO2 to the atmosphere between approximately 13,800 and 15,600 years ago. This observation is most compatible with increased frequency of La Niña conditions during this interval. Hence, increased upwelling in the eastern equatorial Pacific may have played an important role in the rise in atmospheric CO2 during the last deglaciation.


Growth Inhibitory Mechanism of Contact-independent Antifungal TM-I-3 Bacillus sporothermodurans Strain against Aspergillus fumigatus and Cladosporium cladosporioides.
We previously identified a new Bacillus sporothermodurans strain, TM-I-3, which produces volatile compounds that show potent inhibitory activity against certain types of fungi, including Aspergillus fumigatus and Cladosporium cladosporioides. Non-contact antifungals derived from this bacterium may provide multidirectional inhibition and may be useful in disease prevention. This study is aimed at identifying the stage of fungal growth that is inhibited by TM-I-3 to elucidate the mechanism of its contact-independent antifungal activity. We evaluated mycelial growth and the gross fungal colony areas after 7 days in each experimental group varying the time in the proximity of TM-I-3 for 24 hours each. The fungal growth inhibition assay showed that TM-I-3 inhibited spore germination: the lag phase in the sigmoid growth curve. The present study demonstrated that TM-I-3 might be an effective fungistatic agent against pathogenic and allergenic fungi.


Hydrophobic interactions control zymogen activation in the trypsin family of serine proteases.
Trypsinogen is converted to trypsin by the removal of a peptide from the N terminus, which permits formation of a salt bridge between the new N-terminal Ile (residue 16) and Asp194. Formation of this salt bridge triggers a conformational change in the "activation domain" of trypsin, creating the S1 binding site and oxyanion hole. Thus, the activation of trypsinogen appears to represent an example of protein folding driven by electrostatic interactions. The following trypsin mutants have been constructed to explore this problem: Asp194Asn, Ile16Val, Ile16Ala, and Ile16Gly. The bovine pancreatic trypsin inhibitor (BPTI), benzamidine, and leupeptin affinities and activity and pH-rate profiles of these mutants have been measured. The changes in BPTI and benzamidine affinity measure destabilization of the activation domain. These experiments indicate that hydrophobic interactions of the Ile16 side chain provide 5 kcal/mol of stabilization energy to the activation domain while the salt bridge accounts for 3 kcal/mol. Thus, hydrophobic interactions provide the majority of stabilization energy for the trypsinogen to trypsin conversion. The pH-rate profiles of I16A and I16G are significantly different than the pH-rate profile of trypsin, further confirming that the activation domain has been destabilized. Moreover, these mutations decrease kcat/Km and leupeptin affinity in parallel with the decrease in stability of the activation domain. Acylation is selectively decreased, while substrate binding and deacylation are not affected. Together these observations indicate that the stability of protein structure is an important component of transition state stabilization in enzyme catalysis. These results also suggest that active zymogens can be created without providing a counterion for Asp194, and thus have important implications for the elucidation of the structural features which account for the zymogen activity of tissue plasminogen activator and urokinase.


Survey of Similarity-Based Prediction of Drug-Protein Interactions.
Therapeutic activity of a significant majority of drugs is determined by their interactions with proteins. Databases of drug-protein interactions (DPIs) primarily focus on the therapeutic protein targets while the knowledge of the off-targets is fragmented and partial. One way to bridge this knowledge gap is to employ computational methods to predict protein targets for a given drug molecule, or interacting drugs for given protein targets. We survey a comprehensive set of 35 methods that were published in high-impact venues and that predict DPIs based on similarity between drugs and similarity between protein targets. We analyze the internal databases of known PDIs that these methods utilize to compute similarities, and investigate how they are linked to the 12 publicly available source databases. We discuss contents, impact and relationships between these internal and source databases, and well as the timeline of their releases and publications. The 35 predictors exploit and often combine three types of similarities that consider drug structures, drug profiles, and target sequences. We review the predictive architectures of these methods, their impact, and we explain how their internal DPIs databases are linked to the source databases. We also include a detailed timeline of the development of these predictors and discuss the underlying limitations of the current resources and predictive tools. Finally, we provide several recommendations concerning the future development of the related databases and methods.


Single-port transumbilical laparoscopic excision of retroperitoneal schwannoma mimicking a nonfunctional endocrine tumor in the body of the pancreas: a case report.
Schwannomas are benign tumors that arise from neural sheath Schwann cells. Solitary benign schwannoma is generally located in the head and neck and is a rare neoplasm among the tumors of the retroperitoneal space. Reports of laparoscopic excision of retroperitoneal schwannomas have recently been on the increase. However, few cases of single-port laparoscopic excision of these tumors have been reported. Moreover, there are no reports of single-port excision of schwannomas attached to the body of pancreas and around the splenic vessels. This is the first report of a schwannoma lying adjacent to the body of the pancreas between the splenic artery and vein that was excised by single-port laparoscopic surgery. The most notable aspect of our procedure is the use of bipolar forceps. Single-port laparoscopic excision using bipolar forceps is a feasible and safe procedure for retroperitoneal solitary tumors, even when they are close to the splenic artery and vein.


A grading system to evaluate objectively the strength of pre-clinical data of acute neuroprotective therapies for clinical translation in spinal cord injury.
The past three decades have seen an explosion of research interest in spinal cord injury (SCI) and the development of hundreds of potential therapies that have demonstrated some promise in pre-clinical experimental animal models. A growing number of these treatments are seeking to be translated into human clinical trials. Conducting such a clinical trial, however, is extremely costly, not only for the time and money required to execute it, but also for the limited resources that will then no longer be available to evaluate other promising therapies. The decision about what therapies have sufficient pre-clinical evidence of efficacy to justify testing in humans is therefore of utmost importance. Here, we have developed a scoring system for objectively grading the body of pre-clinical literature on neuroprotective treatments for acute SCI. The components of the system include an evaluation of a number of factors that are thought to be important in considering the "robustness" of a therapy's efficacy, including the animal species and injury models that have been used to test it, the time window of efficacy, the types of functional improvements effected by it, and whether efficacy has been independently replicated. The selection of these factors was based on the results of a questionnaire that was performed within the SCI research community. A modified Delphi consensus-building exercise was then conducted with experts in pre-clinical SCI research to refine the criteria and decide upon how to score them. Finally, the grading system was applied to a series of potential neuroprotective treatments for acute SCI. This represents a systematic approach to developing an objective method of evaluating the extent to which the pre-clinical literature supports the translation of a particular experimental treatment into human trials.


The role of interleukin-8 in cancer cells and microenvironment interaction.
Abstract Interleukin (IL)-8, a cytokine of the CXC chemokine family that was originally classified as a neutrophil chemoattractant, is now reported to play an important role in tumor progression and metastasis in a variety of human cancers, including lung cancers. IL-8 biologic activity in tumors and the tumor microenvironment may contribute to tumor progression through its potential function in the regulation of angiogenesis, cancer cell growth and survival, tumor cell motion, leukocyte infiltration and modification of immune responses. Recently, infiltrating macrophages in tumor stroma have been considered to be able to stimulate cancer growth, enhance angiogenesis and promote metastasis, and has prognostic significance in several human cancers. Accumulating evidence also shows that cancer cells and stromal cell interaction can stimulate cancer cells, as well as stromal cells in the expression of IL-8 and other growth factors. Here, we summarize current information about IL-8 biology in human lung cancers and focus on its effect on tumor angiogenesis, regulation of IL-8 expression in tumors, its prognostic significances, the role of tumor infiltrating macrophages in the production of IL-8 in cancer cells and the tumor microenvironment, gene expression profiles after cancer cell-stromal cell interaction, and the effect of a variety anti- inflammatory drugs on the modification of IL-8 and other gene expressions in cancer cells and the tumor microenvironment in lung cancers.


Graft survival and its determinants: a 3 year national experience with liver transplantation in Israel.
There is a dearth of organs for liver transplantation in Israel. Enhancing our understanding of factors affecting graft survival in this country could help optimize the results of the transplant operation. To report 3 years national experience with orthotopic liver transplantation, and to evaluate patient and perioperative risk factors that could affect 1 year graft survival. The study related to all 124 isolated adult liver transplantations performed in Israel between October 1997 and October 2000. Data were abstracted from the medical records. One-year graft survival was described using the Kaplan-Meier survival curve and three multivariate logistic regression models were performed: one with preoperative case-mix factors alone, and the other two with the addition of donor and operative factors respectively. Of the 124 liver transplantations performed, 32 failed (25.8%). The 1 year survival was lower than rates reported from both the United States and Europe but the difference was not significant. Of the preoperative risk factors, recipient age > 60 years, critical condition prior to surgery, high serum bilirubin and serum hemoglobin < or = 10 g/dl were independently associated with graft failure, adjusting for all the other factors that entered the logistic regression equation. Extending the model to include donor and operative factors raised the C-statistic from 0.79 to 0.87. Donor age > or = 40, cold ischemic time > 10 hours and a prolonged operation (> 10 hours) were the additional predictors for graft survival. A MELD score of over 18 was associated with a sixfold increased risk for graft failure (odds ratio = 6.5, P = 0.001). Graft survival in Israel is slightly lower than that reported from the U.S. and Europe. Adding donor and operative factors to recipient characteristics significantly increased our understanding of 1 year survival of liver grafts.


Intensity modulated radiotherapy induces pro-inflammatory and pro-survival responses in prostate cancer patients.
Intensity modulated radiotherapy (IMRT) is one of the modern conformal radiotherapies that is widely used within the context of cancer patient treatment. It uses multiple radiation beams targeted to the tumor, however, large volumes of the body receive low doses of irradiation. Using γ-H2AX and global genome expression analysis, we studied the biological responses induced by low doses of ionizing radiation in prostate cancer patients following IMRT. By means of different bioinformatics analyses, we report that IMRT induced an inflammatory response via the induction of viral, adaptive, and innate immune signaling. In response to growth factors and immune-stimulatory signaling, positive regulation in the progression of cell cycle and DNA replication were induced. This denotes pro-inflammatory and pro-survival responses. Furthermore, double strand DNA breaks were induced in every patient 30 min after the treatment and remaining DNA repair and damage signaling continued after 18-24 h. Nine genes belonging to inflammatory responses (TLR3, SH2D1A and IL18), cell cycle progression (ORC4, SMC2 and CCDC99) and DNA damage and repair (RAD17, SMC6 and MRE11A) were confirmed by quantitative RT-PCR. This study emphasizes that the risk assessment of health effects from the out-of-field low doses during IMRT should be of concern, as these may increase the risk of secondary cancers and/or systemic inflammation.


Ileocecal sphincter contraction to colonic distension: a tachykinin-mediated spinal reflex.
The ileocecal sphincter in the cat demonstrates a reflex contraction to colonic distension. This study investigates the pathway mediating this reflex in the intact bowel using an in vivo model. The ileocecal sphincter (ICS) and distal ileal intraluminal pressures were recorded in fasted chloralose-anesthetized cats. Colonic balloon distension caused a slight, but significant, ileal inhibition with a maximum decrease from resting ileal pressure by 2.6 +/- 0.76 mmHg (P less than 0.005) to 3 ml distension. A volume-dependent contraction at the ICS was seen with a maximal contraction of 16.8 +/- 2.2 mmHg (P less than 0.005) with 4 ml distension. The reflex ICS contraction was inhibited by tetrodotoxin and phentolamine but not by bilateral cervical vagotomy, naloxone, atropine, or trimethaphan camsylate. The reflex contraction at the ICS was inhibited by substance P tachyphylaxis. Substance P tachyphylaxis did not inhibit ICS contraction to phenylephrine. The substance P antagonist, [DArg1,DTrp7,9,Leu11]substance P failed to antagonize substance P and failed to inhibit the ICS contractile response to colonic balloon distension. Spinal anesthesia inhibited this reflex. We have thus demonstrated that the ICS reflex contraction to colonic balloon distension in the intact bowel is mediated by an extrinsic spinal neural pathway involving both tachykinin and catecholamines as neurotransmitters.


Clinical features of hypersensitivity reactions to carboplatin.
To characterize the clinical features of carboplatin-associated hypersensitivity reactions. Patients with gynecologic malignancies treated at the Cleveland Clinic Foundation from June 1995 through July 1998 who experienced a carboplatin-associated hypersensitivity reaction were the subjects of this evaluation. Of the 205 patients treated with carboplatin during this time period, 24 (12%) developed a carboplatin hypersensitivity reaction. The median number of platinum (carboplatin plus cisplatin) courses for the first episode was eight (range, six to 21). Only three patients (13%) developed this toxicity during their initial chemotherapy regimen, with the remainder experiencing a reaction during their second (n = 15) or third (n = 6) carboplatin treatment program for recurrent disease. Thirteen patients (54%) developed at least moderately severe symptoms (diffuse erythroderma, tachycardia, chest tightness, wheezing, facial swelling, dyspnea, hypertension, or hypotension). In approximately one half of patients, the reaction developed after more than 50% of the carboplatin had been infused. Only one of three patients was successfully treated with the agent upon rechallenge. Carboplatin hypersensitivity reactions develop in patients who have been extensively pretreated with the agent. The clinical features are highly variable, but they are sufficiently different from those noted after the administration of paclitaxel that it should not be difficult to distinguish between reactions to the two agents. As carboplatin is increasingly used as initial and second-line chemotherapy of ovarian cancer and other malignancies, it can be anticipated that hypersensitivity reactions to the drug will become a more common and difficult clinical management issue.


Training Community Health Workers to Enhance Disaster Resilience.
Community health workers (CHWs) have significant potential to contribute to public health in the United States by promoting disaster preparedness, speeding postdisaster recovery, and building disaster resilience in their communities. To maximize this potential, however, they must undergo rigorous and relevant training. As part of the Gulf Region Health Outreach Program, an appropriate curriculum was developed and delivered in several training sessions conducted from 2013 to 2016. This article provides insights into the primary issues associated with such training and offers a detailed elaboration of the basic and specialized curricula as presented and adapted over the course of the program. We present lessons learned from these training experiences, as reflected in participants' initial ratings and comments, training staff debriefings, and feedback from CHWs working in the field. Informed by this feedback, as well as additional research and conceptual development, we offer recommendations aimed at expanding and refining CHW training curricula in the areas of chronic disease, psychosocial symptoms, community resilience, and environmental health. In addition to curriculum changes, we review policy implications aimed at promoting and facilitating the inclusion of CHWs in disaster response and recovery teams.


Treatment of Crohn's disease with certolizumab pegol.
Biologic therapies have revolutionized the treatment of Crohn's disease (CD). Targeting TNF-alpha with monoclonal antibodies has changed the therapeutic landscape for tackling refractory and complicated CD. Intravenous use of infliximab, a chimeric monoclonal antibody to TNF-alpha is, however, limited by the occurrence of adverse events, infusion reactions, infectious complications, aggravation of heart failure, the occurrence of neurological demyelinating conditions and induction of rare malignancies. The incremental development of next-generation TNF-alpha antibodies and binding proteins through antibody-engineering techniques has followed, with the aim of producing efficacious drugs that are less expensive to produce, have a convenient route of administration and have fewer side effects. Certolizumab pegol (CDP870, Cimzia) is an engineered humanized anti-TNF-alpha antibody Fab fragment that minimizes the protein component and is conjugated to polyethylene glycol. Clinical studies have demonstrated efficacy in the treatment of moderate-to-severe active CD. Reported adverse events in the clinical trial program have been largely of mild-to-moderate severity, and occurred at similar frequencies in the active-treatment and placebo groups. Certolizumab pegol will be a useful addition to the armamentarium of biologic agents that can be used for the long-term treatment of CD.


A histone deacetylase complex mediates biofilm dispersal and drug resistance in Candida albicans.
Biofilms are resilient, surface-associated communities of cells with specialized properties (e.g., resistance to drugs and mechanical forces) that are distinct from those of suspension (planktonic) cultures. Biofilm formation by the opportunistic human fungal pathogen Candida albicans is medically relevant because C. albicans infections are highly correlated with implanted medical devices, which provide efficient substrates for biofilm formation; moreover, biofilms are inherently resistant to antifungal drugs. Biofilms are also important for C. albicans to colonize diverse niches of the human host. Here, we describe four core members of a conserved histone deacetylase complex in C. albicans (Set3, Hos2, Snt1, and Sif2) and explore the effects of their mutation on biofilm formation. We find that these histone deacetylase complex members are needed for proper biofilm formation, including dispersal of cells from biofilms and multifactorial drug resistance. Our results underscore the importance of the physical properties of biofilms in contributing to drug resistance and dispersal and lay a foundation for new strategies to target biofilm dispersal as a potential antifungal intervention. Through the formation of biofilms--surface-associated communities of cells--microorganisms can establish infections, become drug resistant, and evade the host immune system. Here we investigate how four core members of a conserved histone deacetylase complex mediate biofilm formation by Candida albicans, the major fungal pathogen of humans. We show that this histone deacetylase complex is required for biofilm dispersal, a process through which cells leave the biofilm to establish new infections. We also show that the deacetylase complex mediates biofilm drug resistance. This work provides new insight into how the physical properties of biofilms affect dispersal and drug resistance and suggests new potential antifungal strategies that could be effective against biofilms.


Importance of mega-environments in evaluation and identification of climate resilient maize hybrids (Zea mays L.).
Multi-location experiments on maize were conducted from 2016 to 2019 at ten locations distributed across two agro-climatic zones (ACZ) i.e., ACZ-3 and ACZ-8 of Karnataka, India. Individual analysis of variance for each location-year combination showed significant differences among the hybrids; similarly, combined analysis showed a higher proportion of GE interaction variance than due to genotype. Mega-environments were identified using biplot approaches such as AMMI, GGE, and WAASB methodologies for the years 2016 to 2019. The BLUP method revealed a high correlation between grain yield and stability indices ranging from 0.67 to 1.0. Considering all three methods together, the three location pairs Arabhavi-Belavatagi, Bailhongal-Belavatagi, and Hagari-Sirguppa had three occurrences in the same mega-environment with a value of 0.67, and these location combinations consistently produced winning genotypes. Among the common winning genotypes identified, it was G7 during 2016 and 2017 and G10 during 2018 and 2019, based on WAASBY. The likelihood of Arabhavi-Nippani, Hagari-Mudhol, and Dharwad-Hagari occurring in the same mega-environment is minimal because they did not share the same winning genotype, with the exception of a small number of events. Despite being in the same agro-climatic zone, Arabhavi, Hagari, and Mudhol rarely had a winning genotype in common. An agro-climatic zone is grouped based on climatic and soil conditions which doesn't consider GE interaction of cultivars thus, releasing the cultivars for commercial cultivation considering mega environments pattern would enhance the yield for the given target region.


Clinical ethics and the quality initiative: a pilot study for the empirical evaluation of ethics case consultation.
The Institute of Medicine's quality imperatives include the need to provide safe, effective, patient-centered, timely, efficient, and equitable care. Less attention has been paid to quality metrics as they relate to the assessment of clinical ethics consultation and its impact on care. A better understanding of how ethics consultation influences the quality of care might identify opportunities for improvement. A descriptive pilot study, involving 7 hospitals in the New York-Presbyterian Healthcare System, was conducted to identify key elements of the ethics consultative process that might impact clinical and psychosocial outcomes. A majority of consults involved medical or intensive care unit patients and end-of-life decision making; 75.5% had or received a do-not-resuscitate order, 90.6% lacked decision-making capacity, 43.4% had an advance directive. Conflict existed in a majority. Future research should include surrogate decision making, patients on nonmedical services who may have unrecognized ethical dilemmas, and the role of conflict in clinical care.


[Current treatment with oral antidiabetic agents].
In the large majority of type 2 diabetics, the initial phase of the disease is characterized by insulin resistance. A primary insulin secretion disorder is seen only in normal-weight patients, and requires a differentiated therapeutic approach. Glinides make possible flexible meal-oriented stimulation of insulin secretion. Insulin resistance can be influenced by insulin sensitizers. In the overweight patient, biguanides (metformin) effectively lower blood sugar, either alone or in combination with other oral antidiabetic agents. Acarbose, and glitazone can delay progression to diabetes. Furthermore, acarbose, biguanides, and in particular glitazone, reduce cardiovascular events. For normal-weight patients, sulfonylureas are considered the first-line drug for monotherapy. Progressive insulin secretion deficiency and usually persistent insulin resistance requires insulin substitution in combination with oral antidiabetic agents or as conventional/intensified insulin therapy.


Evaluation of ultrasonic atomization as a new approach to prepare ionically cross-linked chitosan microparticles.
Ultrasonic atomization was evaluated as a new approach for the preparation of ionically cross-linked controlled-release chitosan microparticles loaded with theophylline as the model drug, using tripolyphosphate (TPP) as counter-ion. It was possible to nebulize both 2% and 3% (w/v) chitosan solutions as a function of their viscosity, usually not processed by employing the conventional nebulizer. The results of the chitosan molecular characterization using the SEC-MALS analysis revealed that ultrasonic atomization caused a certain depolymerization, probably due to the main chain scission of the 1,4-glycosidic bond; however, Fourier transform-infrared spectroscopy revealed the absence of other chemical modifications. The ultrasonic atomization allowed preparation of TPP cross-linked chitosan microparticles mostly ranging between 50 and 200 mum. As regards manufacturing parameters, the linking time and washing medium were found to affect the properties of the microparticles, while the stirring rate of the TPP solution did not show any influence. The evaluation of the formulation variables revealed that chitosan concentration strongly affected both the feasibility of the ultrasonic atomization and the drug release. All the microparticles showed an encapsulation efficiency of > 50 % and, after an initial burst effect, a controlled release of drug for 48 h. In conclusion, the ultrasonic atomization could be proposed as a robust and innovative single-step procedure with scale-up potential to successfully prepare ionically cross-linked chitosan microparticles.


Chemical Burns of the Eye.
Chemical burns of the eye are one of the most common eye injuries. The extent of the ocular surface damage is influenced by the type, temperature, volume, and pH of the corrosive substance and duration of exposure. Limbal ischemia found on eye assessment is the primary determinant of eventual visual outcome. Eye irrigation must be instituted immediately at the scene of exposure and continued in the emergency department to reduce visual impairment. Traditionally lactated Ringer's and normal saline have been used as irrigation fluids, although one systematic review demonstrates similar outcomes with other irrigation fluids. The Morgan Lens is a device that can be utilized to allow the provider to perform "hands free" eye irrigation. Complications of chemical burns are more common with alkali burns as these substances destroy the corneal epithelium and allow this corrosive base substance to penetrate deeper into the cornea.


Carbon quantum dots as novel sensitizers for photoelectrochemical solar hydrogen generation and their size-dependent effect.
As a result of global energy needs, much research has been devoted to the conversion of solar energy to various usable forms, such as chemical energy in the form of hydrogen via water splitting. To make the conversion methods efficient, economically practical, and industrially scalable, sensitizers capable of utilizing visible and near infrared (IR) light need to be developed. Herein, water-soluble, colloidally stable carbon quantum dots (CQDs) are successfully synthesized by a facile one-step alkali-assisted electrochemical method. Owing to their broad visible light absorption, upconversion luminescence properties and efficient electron injection to TiO2, these CQDs can be used as the sensitizer for photoelectrochemical cells and show an optimized photocurrent of 1.2 mA cm(-2) at 0 V versus Ag/AgCl under 100 mW cm(-2) simulated sunlight. The above results indicate that the elementally abundant and environmentally friendly CQDs, as a novel sensitizer, can surely be employed to make full use of the visible spectrum of sunlight for their application in photovoltaic devices.


Pronounced loss of cell nuclei and anisotropic deformation of thick sections.
The local deformation and variations in section thickness are studied in 100-microm thick vibratome sections of well-fixed human brain tissue. During processing, including drying on glass slides, the section thickness is reduced to less than half, but close to the edges there is less shrinkage of the section thickness. Close to both surfaces there is a pronounced reduction in the number of neuronal nucleoli. At the scale of the original section, the upper 15 microm and the lower 10 microm are depleted. The loss is most pronounced at the upper surface, which is unprotected during processing. In the central 70% of the section height, where one would ordinarily use an optical disector for sampling, there is no indication of non-uniform shrinkage. The simplest explanation for the observed loss of nucleoli is that all cells opened by the knife may lose their nuclei across an unprotected section surface. The observations do not generalize to other tissues and other preparation techniques, but illustrate the magnitude of some of the problems for uniform sampling and unbiased estimation in very thick sections. The uniform optical disector sampling of nucleoli in thick sections, as opposed to that of cell nuclei, raises a special problem, which is discussed briefly.


Effect of Dry Needling Treatment on Tibial Musculature in Combination with Neurorehabilitation Treatment in Stroke Patients: Randomized Clinical Study.
(1) Background: Introducing ultrasound-guided dry needling to neurorehabilitation treatments increases the beneficial effects of therapy. The aim of this study was to compare the effects of including an ultrasound-guided dry needling session in neurorehabilitation treatment on spasticity and gait-balance quality versus neurorehabilitation treatment in subjects who had suffered a stroke. (2) Methods: A single-blind, randomized clinical trial was conducted. Thirty-six patients who had suffered a stroke in the right middle cerebral artery signed the informed consent for participation in the study. Twenty patients finally participated and were randomly assigned to the control group (neurorehabilitation treatment) or experimental group (neurorehabilitation treatment plus ultrasound-guided dry needling). Pre-treatment and post-treatment data were collected on the same day. The experimental group (n = 10) first underwent an ultrasound-guided dry needling intervention on the tibialis anterior and tibialis posterior musculature, followed by neurorehabilitation treatment; the control group (n = 10) underwent their corresponding neurorehabilitation without the invasive technique. Pre-treatment and post-treatment measurements were taken on the same day, assessing the quality of balance-gait using the "Up and Go" test and the degree of spasticity using the Modified Modified Ashworth Scale. (3) Results: The patients who received neurorehabilitation treatment plus ultrasound-guided dry needling showed a greater decrease in spasticity in the tibial musculature after the neurorehabilitation treatment session (p < 0.001), improving balance and gait (p < 0.001). (4) Conclusions: An ultrasound-guided dry needling session combined with neurorehabilitation treatment reduced spasticity and improved balance and gait in stroke patients.


Reservation Lands as a Protective Social Factor: An Analysis of Psychological Distress among Two American Indian Tribes.
The unique physical, cultural, and ecological location of U.S. American Indian reservations simultaneously presents risks for mental health and offers sources of resilience to Native peoples. Using survey data from two American Indian tribes, we explore whether the length of one's life spent on a reservation is associated with lower odds of psychological distress. In both tribes, we find that individuals who live a vast majority of their lives on the reservation have lower odds of psychological distress than individuals who spent portions of their life off or near the reservation. These findings suggest a need to reframe the perception of life experience on tribal reservations but also call for a more nuanced investigation of the life experience of American Indians. This study illustrates the importance of deeply exploring the relationship that American Indians have with their tribal reservation lands.