Identification and characterization of temperature-sensitive mild mutations in three Japanese patients with nonsevere forms of very-long-chain acyl-CoA dehydrogenase deficiency.
Very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is clinically classified into severe, intermediate, and myopathic forms. We identified mutations in three unrelated Japanese patients with VLCAD deficiency: two with the myopathic form and one with the intermediate form, all compound heterozygotes of K264E/M437V, A416T/1798delA, and P89S/IVS16-3delAA, respectively. We characterized four missense mutations, K264E, M437V, A416T, and P89S, by transisent expression analysis, using SV40-transformed fibroblasts derived from a VLCAD-null patient, as recipient cells. In transient expression of the wild-type VLCAD cDNA, VLCAD activity at 30 degrees C was higher than at 37 degrees C. Moreover, this temperature-sensitive character is more evident in all the mutant proteins tested than in wild type. Based on characterization of the five missense mutations identified in four Japanese patients, including data on one patient with the myopathic form previously reported, patients with the nonsevere forms (intermediate or myopathic forms) have missense mutations with residual activities in at least one allele. Expression analysis at 30 degrees C may be more useful for evaluating these missense mutations, compared with that at 37 degrees C.


Strumal carcinoid tumor of the ovary: a case exhibiting severe constipation associated with PYY.
Primary carcinoid tumor of the ovary is uncommon and represents less than 0.1% of ovarian malignancy. Recently, it was reported that the strumal carcinoid tumor may be complicated by severe constipation as one symptom of the carcinoid syndrome. A 50-year-old nulliparous woman complained of persisting constipation and abdominal distention with pelvic mass, raising the possibility of ovarian tumor. The sugically resected tumor was diagnosed as strumal carcinoid tumor. Her long-lasting severe constipation completely disappeared after tumor removal but recurred with recurrent hepatic disease. The tumor cells were positive for PYY, a peptide hormone that has a strong inhibitory effect on intestinal motility, by immunohistochemical stain. Our case provides the more convincing information to indicate that PYY protein, produced by ovarian tumor cells in the trabecular carcinoid component, may be associated with severe constipation.


A method of predicting adult height and obesity in long-term survivors of childhood acute lymphoblastic leukemia.
Short stature and obesity have been reported among long-term survivors of childhood acute lymphocytic leukemia (ALL). We examined factors that contribute to these adverse sequelae. Serial height and weight measurements were analyzed for 91 long-term survivors who were treated for ALL between 1967 and 1975 at a single institution. These patients were all younger than 12 years at diagnosis, were in continuous complete remission, had reached final height, and had height and weight measurements within 1 year of age 18 years. They had received craniospinal (n = 33) or cranial irradiation (n = 58) to total doses of 24 Gy as CNS prophylaxis. Standard deviation scores (SDS) were used to reflect the deviation of height and weight measurements from population means, and the body mass index (BMI; weight divided by height squared) was used in assessing obesity at age 18 years. Short stature (less than fifth percentile) was seen in 41 patients (45%), and obesity (BMI greater than or equal to 24 kg/m2) in 35 (38%). Regression formulae were developed that explain 65% and 62% of the variability in patient height and BMI, respectively. Risk factors were identified for abnormally short stature, which was defined to be a decrease of 1.5 SDS in height from diagnosis to age 18 years. These factors include younger age and above-average height for age at diagnosis (height SDS greater than 0), craniospinal irradiation, and greater decrease in height SDS during antileukemic therapy. Risk factors for obesity at age 18 years include weight SDS greater than 0 and greater than height SDS at 1 year after the end of chemotherapy.


Effects of rearing temperature on immune functions in sockeye salmon (Oncorhynchus nerka).
To determine if the defences of sockeye salmon (Oncorhynchus nerka) raised in captivity are affected by the rearing temperature or their life-cycle stage, various indices of the humoral and cellular immune functions were measured in fish reared at either 8 or 12 degrees C for their entire life-cycle. Measures of humoral immunity included the commonly used haematological parameters, as well as measurements of complement, and lysozyme activity. Cellular assays quantified the ability of macrophages from the anterior kidney to phagocytise Staphylococcus aureus cells, or the activities of certain bactericidal systems of those cells. The T-dependent antibody response to a recombinant 57 kDa protein of Renibacterium salmoninarum was used to quantify the specific immune response. Fish were sampled during the spring and fall of their second, third and fourth years, corresponding to a period that began just before smolting and ended at sexual maturation. Fish reared at 8 degrees C tended to have a greater percentage of phagocytic kidney macrophages during the first 2 years of sampling than the fish reared at 12 degrees C. During the last half of the study the complement activity of the fish reared at 8 degrees C was greater than that of the 12 degrees C fish. Conversely, a greater proportion of the blood leucocytes were lymphocytes in fish reared at 12 degrees C compared to the fish reared at 8 degrees C. Fish reared at 12 degrees C also produced a greater antibody response than those reared at 8 degrees C. Results suggested that the immune apparatus of sockeye salmon reared at 8 degrees C relied more heavily on the non-specific immune response, while the specific immune response was used to a greater extent when the fish were reared at 12 degrees C. Although a seasonal effect was not detected in any of the indices measured, varying effects were observed in some measurements during sexual maturation of fish in both temperature groups. At that time there were dramatic decreases in complement activity and lymphocyte numbers. This study was unique in its scope because it was the first quantitative assessment of salmon immune functions for an entire life-cycle.


Sequence of ovine Ig gamma 2 constant region heavy chain cDNA and molecular modelling of ruminant IgG isotypes.
Ovine mesenteric lymph node mRNA was used for PCR amplification of DNA coding for immunoglobulin gamma 1 and gamma 2 heavy chain constant regions. Primers complementary to regions of CH1 conserved between ruminants were used for upstream priming, with downstream priming on the poly-A segment. PCR products of the appropriate length were cloned and gamma positive clones selected with a CH1 conserved-region probe. Of these, gamma 1 clones were positively selected and gamma 2 clones negatively selected with a gamma 1 hinge-specific probe. Ovine gamma 2 cDNA has 93% identity of nucleotides with ovine gamma 1. Both ovine gamma 1 and gamma 2 CH1 domains encoded two consecutive cysteine residues (Cys-127, -128, Kabat numbering), an arrangement which is deduced to form a pair of disulphide bridges, one to the L chain and one as an intra-chain bridge to the uppermost Cys of the hinge, as in rabbit and goat IgG. The majority of the differences between the isotypes occur in the hinge region and an evolutionary pattern for ruminant IgG hinges can now be identified. IgG1 isotypes are typical, with hinges containing the C-terminal Cys-Pro motif, but deletion and replacement of nucleotides (in the ancestral gene) of ruminant gamma 2 has shortened the IgG2 hinge, removing the Cys-Pro motif and the consensus high affinity Fc gamma RI receptor motif at the start of CH2. An N-terminal glycosylation site and the peptide motif for complement C1q binding are present in CH2 of both isotypes. The hinge regions of gamma 1 and gamma 2 and predicted structures for ovine IgG1 and IgG2 have been modelled. Close apposition of Fab and Fc in IgG2 produces steric hindrance at the normally accessible Fab/hinge/Fc interface; the structural differences between the ruminant isotypes form a basis for understanding some of the differences in their effector properties.


Cross-phenotype association tests uncover genes mediating nutrient response in Drosophila.
Obesity-related diseases are major contributors to morbidity and mortality in the developed world. Molecular diagnostics and targets of therapies to combat nutritional imbalance are urgently needed in the clinic. Invertebrate animals have been a cornerstone of basic research efforts to dissect the genetics of metabolism and nutrient response. We set out to use fruit flies reared on restricted and nutrient-rich diets to identify genes associated with starvation resistance, body mass and composition, in a survey of genetic variation across the Drosophila Genetic Reference Panel (DGRP). We measured starvation resistance, body weight and composition in DGRP lines on each of two diets and used several association mapping strategies to harness this panel of phenotypes for molecular insights. We tested DNA sequence variants for a relationship with single metabolic traits and with multiple traits at once, using a scheme for cross-phenotype association mapping; we focused our association tests on homologs of human disease genes and common polymorphisms; and we tested for gene-by-diet interactions. The results revealed gene and gene-by-diet associations between 17 variants and body mass, whole-body triglyceride and glucose content, or starvation resistance. Focused molecular experiments validated the role in body mass of an uncharacterized gene, CG43921 (which we rename heavyweight), and previously unknown functions for the diacylglycerol kinase rdgA, the huntingtin homolog htt, and the ceramide synthase schlank in nutrient-dependent body mass, starvation resistance, and lifespan. Our findings implicate a wealth of gene candidates in fly metabolism and nutrient response, and ascribe novel functions to htt, rdgA, hwt and schlank.


Assessing the value of electronic prescribing in ambulatory care: a focus group study.
Drug allergy and interaction alerts are a core function of most electronic prescribing (e-prescribing) systems. To characterize the value of e-prescribing and medication safety alerts, especially in small and medium-size practices, we undertook a hypothesis-generating focus group study of Massachusetts clinicians. We sought to understand the reasons for adoption and use of e-prescribing, as well as clinicians' complaints about and perceived benefits of drug allergy and interaction alerts. We recruited 25 Massachusetts clinicians to participate in three focus groups regarding the use and value of e-prescribing and medication safety alerts. The participants included high-volume (>100 electronic scripts per month) physicians, nurse practitioners, and practice assistants in family practice, internal medicine, pediatrics, and subspecialty practices who used a common commercial e-prescribing system. Most clinicians were in small and medium-size group practices. Participants were, on average, 25 years post-medical school graduation (range 8-36), had used e-prescribing for 2.5 years (range 1.0-5.5), and wrote the majority (89%, range 15-100%) of prescriptions electronically. The participants' decision to adopt e-prescribing was driven largely by financial incentives offered by insurers, and was viewed as a step toward implementation of an electronic medical record. Although participants agreed that the system was easy to learn, few anticipated efficiencies were realized until clinicians configured the device to meet their needs. The participants were ambivalent about whether e-prescribing improved their own or overall office efficiency, and--in the absence of payer incentives--few were willing to pay for the systems out-of-pocket. The most valuable aspects of e-prescribing were the ease of changing doses, renewing prescriptions, ensuring legibility, and transmitting prescriptions to in- and out-of-state pharmacies. Participants were dissatisfied with the unreliability of transmitting prescriptions successfully to the pharmacy, and with their inability to merge duplicate patient entries, to create a comprehensive, allprescriber medication list, to write prescriptions for commonly ordered medications and supplies, and to enter allergy information into the system. Participants were critical of the volume of drug allergy and interaction alerts. Many alerts were of trivial clinical significance or were generated by interactions with out-of-date medications. As a result, many clinicians habitually ignored these alerts. Alerts were most helpful to clinicians who were unfamiliar with a particular drug or patient. Although alerts rarely led the clinicians to abort or alter a prescription, alerts did prompt clinicians to counsel patients about medication side effects, to educate themselves about potential interactions, to check physical examination findings, or to order laboratory tests. Despite problems, few clinicians were willing to forego receiving alerts for fear that they would miss a potentially dangerous drug interaction. Electronic prescribing is a potential boon to ambulatory medical practice, although its value may be compromised by inappropriate and irrelevant medication safety alerts and by features of the e-prescribing system that prove burdensome to frontline clinicians. While alerts infrequently result in changed or aborted prescriptions, they may trigger a variety of other provider behaviors that help to ensure safe care.


No Change of Pneumocystis jirovecii Pneumonia after the COVID-19 Pandemic: Multicenter Time-Series Analyses.
Consolidated infection control measures imposed by the government and hospitals during COVID-19 pandemic resulted in a sharp decline of respiratory viruses. Based on the issue of whether Pneumocystis jirovecii could be transmitted by airborne and acquired from the environment, we assessed changes in P. jirovecii pneumonia (PCP) cases in a hospital setting before and after COVID-19. We retrospectively collected data of PCP-confirmed inpatients aged ≥18 years (N = 2922) in four university-affiliated hospitals between January 2015 and June 2021. The index and intervention dates were defined as the first time of P. jirovecii diagnosis and January 2020, respectively. We predicted PCP cases for post-COVID-19 and obtained the difference (residuals) between forecasted and observed cases using the autoregressive integrated moving average (ARIMA) and the Bayesian structural time-series (BSTS) models. Overall, the average of observed PCP cases per month in each year were 36.1 and 47.3 for pre- and post-COVID-19, respectively. The estimate for residuals in the ARIMA model was not significantly different in the total PCP-confirmed inpatients (7.4%, p = 0.765). The forecasted PCP cases by the BSTS model were not significantly different from the observed cases in the post-COVID-19 (-0.6%, 95% credible interval; -9.6~9.1%, p = 0.450). The unprecedented strict non-pharmacological interventions did not affect PCP cases.


Emergence of Thorium-Based Polyoxo Clusters as a Platform for Selective X-ray Dosimetry.
A brand-new application of thorium-bearing clusters in the field of ionizing radiation detection is exemplified by two novel hexanuclear thorium clusters, Th-bppCOO-1 and Th-bppCOO-2, which incorporate carboxylate-functionalized 2,6-di(pyrazol-1-yl)pyridine ligands. Notably, Th-bppCOO-1 is composed of an unprecedented [Th6(OH)4O4(H2O)5]12+ secondary building unit, the Th6 core of which is decorated by five H2O molecules. Furthermore, selective photoluminescence quenching responses of Th-bppCOO-1 and Th-bppCOO-2 toward X-ray over UV radiation have been demonstrated for the first time.


Human RECQL5: guarding the crossroads of DNA replication and transcription and providing backup capability.
DNA helicases are ubiquitous enzymes that catalyze unwinding of duplex DNA and function in all metabolic processes in which access to single-stranded DNA is required, including DNA replication, repair, recombination and RNA transcription. RecQ helicases are a conserved family of DNA helicases that display highly specialized and vital roles in the maintenance of genome stability. Mutations in three of the five human RecQ helicases, BLM, WRN and RECQL4 are associated with the genetic disorders Bloom syndrome, Werner syndrome and Rothmund-Thomson syndrome that are characterized by chromosomal instability, premature aging and predisposition to cancer. The biological role of human RECQL5 is only partially understood and RECQL5 has not yet been associated with any human disease. Illegitimate recombination and replication stress are hallmarks of human cancers and common instigators for genomic instability and cell death. Recql5 knockout mice are cancer prone and show increased chromosomal instability. Recql5-deficient mouse embryonic fibroblasts are sensitive to camptothecin and display elevated levels of sister chromatid exchanges. Unlike other human RecQ helicases, RECQL5 is recruited to single-stranded DNA breaks and is also proposed to play an essential role in RNA transcription. Here, we review the established roles of RECQL5 at the cross roads of DNA replication, recombination and transcription, and propose that human RECQL5 provides important backup functions in the absence of other DNA helicases.


Computed tomography-based radiomics quantification predicts epidermal growth factor receptor mutation status and efficacy of first-line targeted therapy in lung adenocarcinoma.
Biomarkers that predict the efficacy of first-line tyrosine kinase inhibitors (TKIs) are pivotal in epidermal growth factor receptor (EGFR) mutant advanced lung adenocarcinoma. Imaging-based biomarkers have attracted much attention in anticancer therapy. This study aims to use the machine learning method to distinguish EGFR mutation status and further explores the predictive role of EGFR mutation-related radiomics features in response to first-line TKIs. We retrospectively analyzed pretreatment CT images and clinical information from a cohort of lung adenocarcinomas. We entered the top-ranked features into a support vector machine (SVM) classifier to establish a radiomics signature that predicted EGFR mutation status. Furthermore, we identified the best response-related features based on EGFR mutant-related features in first-line TKI therapy patients. Then we test and validate the predictive effect of the best response-related features for progression-free survival (PFS). Six hundred ninety-two patients were enrolled in building radiomics signatures. The 13 top-ranked features were input into an SVM classifier to establish the radiomics signature of the training cohort (n = 514), and the predictive score of the radiomics signature was assessed on an independent validation group with 178 patients and obtained an area under the curve (AUC) of 74.13%, an F1 score of 68.29%, a specificity of 79.55%, an accuracy of 70.79%, and a sensitivity of 62.22%. More importantly, the skewness-Low (≤0.882) or 10th percentile-Low group (≤21.132) had a superior partial response (PR) rate than the skewness-High or 10th percentile-High group (p < 0.01). Higher skewness (hazard ratio (HR) = 1.722, p = 0.001) was also found to be significantly associated with worse PFS. The radiomics signature can be used to predict EGFR mutation status. Skewness may contribute to the stratification of disease progression in lung cancer patients treated with first-line TKIs.


Drought Impact Is Alleviated in Sugar Beets (Beta vulgaris L.) by Foliar Application of Fullerenol Nanoparticles.
Over the past few years, significant efforts have been made to decrease the effects of drought stress on plant productivity and quality. We propose that fullerenol nanoparticles (FNPs, molecular formula C60(OH)24) may help alleviate drought stress by serving as an additional intercellular water supply. Specifically, FNPs are able to penetrate plant leaf and root tissues, where they bind water in various cell compartments. This hydroscopic activity suggests that FNPs could be beneficial in plants. The aim of the present study was to analyse the influence of FNPs on sugar beet plants exposed to drought stress. Our results indicate that intracellular water metabolism can be modified by foliar application of FNPs in drought exposed plants. Drought stress induced a significant increase in the compatible osmolyte proline in both the leaves and roots of control plants, but not in FNP treated plants. These results indicate that FNPs could act as intracellular binders of water, creating an additional water reserve, and enabling adaptation to drought stress. Moreover, analysis of plant antioxidant enzyme activities (CAT, APx and GPx), MDA and GSH content indicate that fullerenol foliar application could have some beneficial effect on alleviating oxidative effects of drought stress, depending on the concentration of nanoparticles applied. Although further studies are necessary to elucidate the biochemical impact of FNPs on plants; the present results could directly impact agricultural practice, where available water supplies are often a limiting factor in plant bioproductivity.


Adjuvant therapy following pancreatic resection for pancreatic duct carcinoma: a prospective randomized study.
This study was made to determine the efficacy of locoregional immunochemotherapy in the treatment of pancreatic ductal carcinoma. From November 1991 to June 1996, eighty patients with a diagnosis of pancreatic duct carcinoma underwent pancreatic resection. Patients were divided into two groups, Group A and Group B. Both groups received a standard operative procedure of extended subtotal pancreatectomy with regional lymphadenectomy of the celiac axis, the hepatoduodenal ligament and the superior mesenteric vessels. However, Group B patients had two arterial catheters implanted at the end of the operative procedure: one via the splenic artery, after its ligation near the origin at the celiac axis and directed towards the spleen; the second catheter was implanted into a side arterial branch of the middle colic artery into the superior mesenteric artery. Group B patients have a significantly greater survival (30 months) compared to Group A patients (16.8 months). The proportion of alive patients between both Groups is much higher for Group's B patients (92% versus 55%). Grading of the tumor, size of the tumor, and presence of positive lymph nodes were seen to be very important factors affecting overall survival in Group A patients, but not in Group B patients. It is impressive that from 25 Group A patients with lymph node involvement, only 8 are presently alive versus 25 alive of 28 total Group B patients with positive lymph nodes. Locoregional immunochemotherapy as an adjuvant modality following pancreatic resection offers impressive advantages in terms of survival regardless of stage, lymph involvement, and tumor size. This therapy deserves further attention and consideration in the treatment of Pancreatic Duct Carcinoma.


Oxalates in oca (New Zealand yam) (Oxalis tuberosa Mol.).
Oca (Oxalis tuberosa Mol.) or New Zealand yam, in common with other members of this genus, contains oxalate, an antinutritive factor. Twelve South American and two New Zealand cultivars of oca were analyzed for total and soluble oxalate contents of the tubers. The range of total oxalate levels was 92-221 mg/100 g of fresh weight. Levels of soluble and total oxalate extracted from the tubers were not significantly different, suggesting that no calcium oxalate is formed in the tubers. The oxalate concentrations obtained in this study for oca suggest that previously reported values are too low and that oca is a moderately high oxalate-containing food. This is the first report of a tuber crop containing moderate to high levels of soluble oxalates in the tubers and no insoluble oxalates.


Surgical treatment of cervical stenotic myelopathy in horses: 73 cases (1983-1992).
Seventy-three horses with cervical stenotic myelopathy underwent cervical vertebral interbody fusion (n = 63) or dorsal laminectomy (n = 10). Neurologic function improved in 77% of horses, and 46% of horses achieved athletic function (racing, race training, or pleasure riding) after cervical vertebral interbody fusion for static and dynamic spinal cord compressive lesions. Neurologic status improved in 4 of 10 horses after dorsal decompression for static compressive spinal cord lesions. The duration of clinical signs prior to surgical intervention was shorter for horses that achieved athletic function or improved by at least 2 neurologic grades than for horses that did not improve in neurologic status or improved 1 neurologic grade after cervical vertebral interbody fusion. The number of cervical spinal cord compressive lesions and age of horses did not affect the long-term surgical outcome of cervical vertebral interbody fusion. Seroma formation, implant failure, right laryngeal hemiplegia, and colitis were nonfatal complications associated with cervical vertebral interbody fusion. Dorsal laminectomy and cervical vertebral interbody fusion of static compressive lesions of the caudal cervical vertebral column were associated with fatal postoperative complications, including vertebral body fracture, spinal cord edema, and implant failure.


Novel Rickettsiella bacterium in the leafhopper Orosius albicinctus (Hemiptera: Cicadellidae).
Bacteria in the genus Rickettsiella (Coxiellaceae), which are mainly known as arthropod pathogens, are emerging as excellent models to study transitions between mutualism and pathogenicity. The current report characterizes a novel Rickettsiella found in the leafhopper Orosius albicinctus (Hemiptera: Cicadellidae), a major vector of phytoplasma diseases in Europe and Asia. Denaturing gradient gel electrophoresis (DGGE) and pyrosequencing were used to survey the main symbionts of O. albicinctus, revealing the obligate symbionts Sulcia and Nasuia, and the facultative symbionts Arsenophonus and Wolbachia, in addition to Rickettsiella. The leafhopper Rickettsiella is allied with bacteria found in ticks. Screening O. albicinctus from the field showed that Rickettsiella is highly prevalent, with over 60% of individuals infected. A stable Rickettsiella infection was maintained in a leafhopper laboratory colony for at least 10 generations, and fluorescence microscopy localized bacteria to accessory glands of the female reproductive tract, suggesting that the bacterium is vertically transmitted. Future studies will be needed to examine how Rickettsiella affects host fitess and its ability to vector phytopathogens.


The growth-inhibitory function of p53 is separable from transactivation, apoptosis and suppression of transformation by E1a and Ras.
p53 is known to suppress oncogenic cell transformation, inhibit cell growth, induce apoptosis and activate and repress gene transcription. To investigate the relationships between these functions, we have examined various mutant forms of p53 for their abilities to perform each activity. This study has shown that growth inhibition is not a prerequisite for apoptotic cell death as these two functions are separate and alternative activities of p53. Additionally, we have demonstrated that the ability of p53 to suppress transformation (by adenovirus E1a and activated Ras) correlates with its ability to induce apoptosis and not with its ability to inhibit cell growth. Although p53 is thought to inhibit growth through the transactivation of p21WAFI, our study has demonstrated that transcriptional activation and repression are neither sufficient nor necessary for growth inhibition. This indicates that p53 has more than one mechanism for inhibiting cell growth and that another type of biochemical function must be involved. Furthermore, we have shown that transcriptional activation and repression may each be necessary, and the combination of these activities may even be sufficient, for p53-dependent apoptosis. In summary, our results have provided new information about the cellular and biochemical mechanisms through which p53 acts as a tumor suppressor.


Serotyping, Genotyping, and Antimicrobial Susceptibility of Ornithobacterium rhinotracheale Isolates from Mexico.
The bacterium Ornithobacterium rhinotracheale is associated with respiratory disease and septicemia in poultry. In this study, 9 reference strains and a total of 23 isolates of O. rhinotracheale from respiratory diseased poultry from Mexico were serotyped and genotyped. Furthermore, the antimicrobial susceptibility of isolates and reference strains of O. rhinotracheale were determined. All isolates belong to serotype A and showed a clonal relationship. All reference strains and isolates were resistant to colistin, fosfomycin, gentamicin, kanamycin, streptomycin, and trimethoprim-sulfamethoxazole. These results should eventually be helpful in planning strategies for the control of O. rhinotracheale infections in poultry in Mexico.


Hypermutability of UV-treated plasmids in dysplastic nevus/familial melanoma cell lines.
Members of cutaneous melanoma (CM) families with dysplastic nevi (DN) are at high risk of developing CM. Using a shuttle vector plasmid, pSP189, cell lines from three patients with CM plus DN were previously found to have elevated post-UV plasmid mutability. To investigate familial occurrence of this cellular phenotype, we examined post-UV plasmid mutability in 31 lymphoblastoid cell lines from 6 familial CM kindreds. In comparison to 16 normal control lines, we found an abnormally elevated post-UV plasmid mutability in cell lines from 13 of 13 patients with CM plus DN (P = 1.5 x 10(-8)) and from 5 of 8 patients with DN only (P = 0.001). Elevated spontaneous plasmid mutation frequency (MF) was also present in cell lines from six of the CM plus DN patients (P = 0.002) and three of the DN-only patients (P = 0.028). However, cell lines from two patients with CM without DN had normal post-UV plasmid MF. Although not specific for CM patients, of 27 cell lines with elevated post-UV plasmid MF, only 8 were from donors who did not have CM + DN or DN (19 of 24 versus 8 of 28; P = 0.0003). This study indicates that post-UV plasmid hypermutability is a laboratory marker for members of melanoma-prone families and suggests that patients with familial CM have a defective mechanism for handling UV-induced DNA damage.


[Urachal diseases in childhood (author's transl)].
26 cases of urachus anomalies are reviewed. Embryological, clinical and therapeutic problems are discussed. The authors point out the importance of a systematic urinary tract evaluation. Relationship between urachus anomalies and "prunebelly" syndrome is considered.


Islet-1 cells are cardiac progenitors present during the entire lifespan: from the embryonic stage to adulthood.
The aim of this study was to longitudinally characterize the distribution of cells actively expressing the progenitor transcription factor islet-1 (Isl1+) during the embryonic life, the postnatal period, and adulthood. In this study, we have used direct immunohistochemical staining toward the protein Isl1 in a longitudinal rat model. Cells actively expressing Isl1 were traced in embryos from gestational day (GD) 11 until adulthood. In early cardiac development (GD 11), the Isl1+ progenitors were located in a greater abundance in the paracardiac regions, areas suggested to be the second heart field. To a lesser extent, Isl1+ cells were present within the bulbotruncal region and the truncus arteriosus. During the following days until GD 15, the Isl1+ cells were mainly observed at the proximal outflow tract (OFT) and at the inflow area of the right atrium. No Isl1+ cells were detected in the left ventricle. Compared with GD 11, more Isl1+ cells seemed to co-express cardiomyocyte markers and a minority of the Isl1+ cells was undifferentiated. Unexpectedly, only few undifferentiated Isl1+ cells were Ki67+ while a lot of TnT+ cardiomyocytes were proliferating in the ventricles. After birth, immature Isl1+ cells were still present in the OFT where they resided until adulthood. Our data suggest that during embryogenesis, Isl1+ cells migrate from extracardiac regions into the proximal part of the heart, proliferating and giving rise to cardioblasts. Unexpectedly, only a minority of the Isl1+ cells while a majority of ventricular cardiomyocytes were proliferating. The Isl1+ cell pool persists into adulthood, which might open up new strategies to repair damaged myocardium.


Multifunctional Therapeutic Cyclodextrin-Appended Dendrimer Complex for Treatment of Systemic and Localized Amyloidosis.
Amyloidosis pathologically proceeds via production of amyloidogenic proteins by organs, formation of protein aggregates through structural changes, and their deposition on tissues. A growing body of evidence demonstrates that amyloidosis generally develops through three critical pathological steps: (1) production of amyloid precursor proteins, (2) amyloid formation, and (3) amyloid deposition. However, no clinically effective therapy that is capable of targeting each pathological step of amyloidosis independently is currently available. Here, we combined therapeutic effects and developed a short hairpin RNA expression vector (shRNA) complex with a cyclodextrin-appended cationic dendrimer (CDE) as a novel multitarget therapeutic drug that is capable of simultaneously suppressing these three steps. We evaluated its therapeutic effects on systemic transthyretin (ATTR) amyloidosis and Alzheimer's disease (AD) as localized amyloidosis, by targeting TTR and amyloid β, respectively. CDE/shRNA exhibited RNAi effects to suppress amyloid protein production and also achieved both inhibition of amyloid formation and disruption of existing amyloid fibrils. The multitarget therapeutic effects of CDE/shRNA were confirmed by evaluating TTR deposition reduction in early- and late-onset human ATTR amyloidosis model rats and amyloid β deposition reduction in AppNL-G-F/NL-G-F AD model mice. Thus, the CDE/shRNA complex exhibits multifunctional therapeutic efficacy and may reveal novel strategies for establishing curative treatments for both systemic and localized amyloidosis.


Stereochemical influence of the ligand on the structure of manganese complexes: implications for catalytic epoxidations.
Manganese complexes of the ligand HphoxCOOR (R=H or Me) have been synthesized and characterized by X-ray analysis, ESI-MS, ligand-field spectroscopy, electrochemistry, and paramagnetic 1H NMR. The ligands, chirally pure or racemic, influence the structures of the complexes formed. Manganese(III) complexes of the ligand HphoxCOOMe are square-pyramidal or octahedral with two ligands bound in a trans fashion in the solid state. The racemic ligand (RS-HphoxCOOMe) as well as the enantiopure ligand (R-HphoxCOOMe) forms manganese complexes with similar solid-state structures. Ligand-exchange reactions occur in solution giving rise to meso complexes as confirmed by ESI-MS and deuteration studies. The manganese(III) complex of R-HphoxCOOH is octahedral, with two dianionic ligands bound in a fac-cct fashion in a tridentate manner. The manganese(III) complex of RS-HphoxCOOH is also octahedral with two dianionic ligands now bound in a trans fashion in a didentate manner and with two water molecules occupying axial sites. The paramagnetic 1H NMR spectra of the complexes have been interpreted on the basis of the relaxation times with the help of the inversion-recovery pulse technique. The binding of imidazole with the metal center depends on the chirality of the ligands in the metal complexes of HphoxCOOMe. Imidazole coordination was found to occur with the metal complex that contains two ligands with the same chirality (R and R) (R-1), while no imidazole coordination was found upon reaction with the metal complex that contains two ligands with opposite chirality (R and S) (RS-1). Epoxidation reactions of various alkenes with H2O2 as the oxidant reveal that the complexes give turnover numbers in the range of 10-35, the epoxide being the major product. The catalytic activity depends on the additives used, and a clear base effect is observed. The turnover numbers have been found to be higher in the complexes where no binding of N-Meim is observed. The latter fact unambiguously shows that imidazole binding is not a prerequisite for higher turnover numbers, in contrast to the Mn-Schiff base catalysts.


Psychiatric morbidity in patients with systemic lupus erythematosus.
We investigated psychiatric morbidity in patients with systemic lupus erythematosus, in a hospital-based study. Thirty patients (23 consecutive out-patients and seven unselected in-patients) were prospectively assessed by a multidisciplinary team for the presence of psychiatric disorders and disease activity. Psychiatric assessment was done with structured interviews. Demographic information was recorded in a structured proforma; all the patients completed the Presumptive Stressful Life Event Scale. A close relative was interviewed in every case. Patients who had psychiatric disorders were compared with the rest with respect to demographic variables, lupus disease activity, use of steroids, and stressful life events. We found a 50% prevalence of psychiatric disorders. The patients with psychiatric disorders were similar to those who had no psychopathology with respect to age, sex, duration of illness, lupus activity and the use of steroids. However, they had experienced more stressful life events in the last year.


Lung cancer in never smokers.
Lung cancer in never smokers (LCINS) is the seventh leading cause of death among solid tumors. The main risk factor for lung cancer is smoking; however, approximately 15% of lung cancer patients have never smoked. LCINS is more frequent in women, irrespective of geographical location, nevertheless, the highest incidence has been found in South-East Asia. The histological incidence of adenocarcinoma is higher in the group of never smokers than squamous cell carcinoma. There is a familial clustering of lung cancer that is more pronounced in never smokers, where the family history was associated with an increased risk. Genome-wide association studies identified certain chromosomal aberrations in LCINS. Furthermore, the oncogenic mutation pattern is distinct in nonsmoking patients: activating mutations of EGFR or anaplastic lymphoma kinase are more frequent. The etiology of LCINS includes several environmental factors as well, such as environmental tobacco smoke, viral and hormonal factors, a variety of pulmonary diseases and certain occupational exposures. It is now established that EGFR-tyrosine kinase inhibitor treatment (erlotinib and geftinib) in lung cancer is more effective in LCINS, owing to the higher incidence of EGFR mutation in nonsmokers. Despite the growing body of information on LCINS in recent years there is a need to further investigate the pathogenesis of this particular lung cancer. Future studies on LCINS should try to tackle the issues of prevention, early diagnosis and the exploration of novel therapeutic targets to combat lung cancer disease.


Symptomatic perineural extension of fungal sinusitis in an immunocompetent person: imaging features.
Perineural spread is a rare mode of spread for fungal infection, even more so in immunocompetent individuals. We report a 21-year-old immunocompetent man in which symptomatic perineural extension of aspergillosis along the maxillary division of trigeminal nerve was accurately diagnosed on imaging.


Histamine-2 receptor antagonists at night improve gastroesophageal reflux disease symptoms for patients on proton pump inhibitor therapy.
While night-time symptoms of gastroesophageal reflux disease (GERD) are common, considerable controversy exists regarding the use of histamine-2 receptor antagonists (H2Ras) for night-time reflux control. Some studies have suggested possible tolerance to H2RA while others have suggested that long-term efficacy of gastric acid control can be maintained with night-time H2RA use. The aim of this study was to identify if GERD patients have sustained symptom improvement with long-term use of night-time H2RA. Records of 56 consecutive GERD patients on twice daily proton pump inhibitor (PPI) and night-time H2RA therapy were reviewed. During a phone interview patients were asked a 5-item questionnaire, which included overall assessment of symptoms, night-time symptoms, sleep disturbance, duration and frequency of therapy. Of the 56 patients, 39 (31 women, mean age 56) completed the questionnaire (15 were not reached and 2 did not recall enough information). All respondents had taken night-time H2RA for at least 1 month (28/39 patients with > 6 months duration) with 33/39 patients taking H2RAs every night. The addition of H2RA led to an improvement in overall symptoms in 28/39 (72%) patients, improvement in night-time reflux symptoms in 25/34 (74%) patients and improvement of GERD-associated sleep disturbance in 18/27 (67%) patients. Five (13%) patients had stopped the H2RA on their own, stating that its efficacy waned after 1 month. Our results suggest that the majority of patients report persistent improvement in GERD symptoms from night-time H2RA use and that possible clinically important tolerance to H2RAs occurs in a small number of patients. Further prospective, placebo-controlled studies may help confirm that there is a role for night-time H2RAs in GERD symptom control.


Acute gastric volvulus: a report of eight cases.
Acute gastric volvulus is an abnormal rotation of the stomach through 1800. This study illustrates a series of 8 patients who underwent operative treatment for acute gastric volvulus. Volvulus was primary in all the cases. Of the 8 patients, 6 had organo-axial (75%) and 2 mesenterio-axial (25%) volvulus. Anterior gastropexy (gastrostomy) was performed in all the cases. There was no mortality and all the patients are doing well after one-year follow up.


Endogenously released 5-hydroxytryptamine depresses the spinal monosynaptic reflex via 5-HT1D receptors.
In the spinal cord, various 5-hydroxytryptamine (5-HT) receptor subtypes are involved in the modulation of motor output. Previously, we have shown that 5-HT1B receptors mediate the monosynaptic reflex depression induced by exogenously applied 5-HT that was formed from the precursor L-5-hydroxytryptophan in spinalized rats. In this study, we determined the effects of endogenous 5-HT, which was released from serotonergic terminals by DL-p-chloroamphetamine, on spinal reflexes. DL-p-chloroamphetamine depressed the monosynaptic reflex and increased the polysynaptic reflex. The depletion of 5-HT abolished the monosynaptic reflex depression, but the increase in polysynaptic reflexes was maintained, suggesting that endogenous 5-HT released by DL-p-chloroamphetamine mediates depression of the monosynaptic reflex in the spinal cord. The depression of the monosynaptic reflex was antagonized by GR127935 (N-[methoxy-3-(4-methyl-l-piperazinyl)phenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)[1,1-biphenyl]-4-carboxamide; 5-HT1B/1D receptor antagonist) and BRL15572 (3-[4-(4-chlorophenyl)piperazin-1-yl]-1,1-diphenyl-2-propanol; 5-HT1D receptor antagonist) but not by isamoltane (5-HT(1B) receptor antagonist). These results suggest that 5-HT released from serotonergic terminals depresses monosynaptic reflex transmission via 5-HT1D receptors.


Light-Regulated Synthesis of Cyclic-di-GMP by a Bidomain Construct of the Cyanobacteriochrome Tlr0924 (SesA) without Stable Dimerization.
Phytochromes and cyanobacteriochromes (CBCRs) use double-bond photoisomerization of their linear tetrapyrrole (bilin) chromophores within cGMP-specific phosphodiesterases/adenylyl cyclases/FhlA (GAF) domain-containing photosensory modules to regulate activity of C-terminal output domains. CBCRs exhibit photocycles that are much more diverse than those of phytochromes and are often found in large modular proteins such as Tlr0924 (SesA), one of three blue light regulators of cell aggregation in the cyanobacterium Thermosynechococcus elongatus. Tlr0924 contains a single bilin-binding GAF domain adjacent to a C-terminal diguanylate cyclase (GGDEF) domain whose catalytic activity requires formation of a dimeric transition state presumably supported by a multidomain extension at its N-terminus. To probe the structural basis of light-mediated signal propagation from the photosensory input domain to a signaling output domain for a representative CBCR, these studies explore the properties of a bidomain GAF-GGDEF construct of Tlr0924 (Tlr0924Δ) that retains light-regulated diguanylate cyclase activity. Surprisingly, circular dichroism spectroscopy and size exclusion chromatography data do not support formation of stable dimers in either the blue-absorbing 15ZPb dark state or the green-absorbing 15EPg photoproduct state of Tlr0924Δ. Analysis of variants containing site-specific mutations reveals that proper signal transmission requires both chromophorylation of the GAF domain and individual residues within the amphipathic linker region between GAF and GGDEF domains. On the basis of these data, we propose a model in which bilin binding and light signals are propagated from the GAF domain via the linker to alter the equilibrium and interconversion dynamics between active and inactive conformations of the GGDEF domain to favor or disfavor formation of catalytically competent dimers.


Hierarchical statistical techniques are necessary to draw reliable conclusions from analysis of isolated cardiomyocyte studies.
It is generally accepted that post-MI heart failure (HF) changes a variety of aspects of sarcoplasmic reticular Ca2+ fluxes but for some aspects there is disagreement over whether there is an increase or decrease. The commonest statistical approach is to treat data collected from each cell as independent, even though they are really clustered with multiple likely similar cells from each heart. In this study, we test whether this statistical assumption of independence can lead the investigator to draw conclusions that would be considered erroneous if the analysis handled clustering with specific statistical techniques (hierarchical tests). Ca2+ transients were recorded in cells loaded with Fura-2AM and sparks were recorded in cells loaded with Fluo-4AM. Data were analysed twice, once with the common statistical approach (assumption of independence) and once with hierarchical statistical methodologies designed to allow for any clustering. The statistical tests found that there was significant hierarchical clustering. This caused the common statistical approach to underestimate the standard error and report artificially small P values. For example, this would have led to the erroneous conclusion that time to 50% peak transient amplitude was significantly prolonged in HF. Spark analysis showed clustering, both within each cell and also within each rat, for morphological variables. This means that a three-level hierarchical model is sometimes required for such measures. Standard statistical methodologies, if used instead, erroneously suggest that spark amplitude is significantly greater in HF and spark duration is reduced in HF. Ca2+ fluxes in isolated cardiomyocytes show so much clustering that the common statistical approach that assumes independence of each data point will frequently give the false appearance of statistically significant changes. Hierarchical statistical methodologies need a little more effort, but are necessary for reliable conclusions. We present cost-free simple tools for performing these analyses.


Anastomotic Troubleshooting.
Anastomotic leak remains a critical and feared complication in colorectal surgery. The development of a leak can be catastrophic for a patient, resulting in overall increased morbidity and mortality. To help mitigate this risk, there are several ways to assess and potentially validate the integrity of a new anastomosis to give the patient the best chance of avoiding this postoperative complication. A majority of anastomoses will appear intact with no obvious sign of anastomotic dehiscence on gross examination. However, each anastomosis should be interrogated before the conclusion of an operation. The most common method to assess for an anastomotic leak is the air leak test (ALT). The ALT is a safe intraoperative method utilized to test the integrity of left-sided colon and rectal anastomoses and most importantly allows the ability to repair a failed test before concluding the operation. Additional troubleshooting is sometimes needed due to technical difficulties with the circular stapler. Problems, such as incomplete doughnuts and stapler misfiring, do occur and each surgeon should be prepared to address them.


Hand skill and hand-eye preference in relation to verbal ability in healthy adult male and female right-handers.
Verbal as well as non-verbal performances were investigated in relation to both hand skill assessed by finger-tapping performances and hand-eye preference in 83 healthy adult right-handers, most of them students. The primary objective of this study was to show better finger-tapping performances in right-handed participants with best verbal IQ values. We found that it was not the non-verbal but the verbal abilities that were related to finger-tapping performances. This was proven, especially as to the left-hand taps. Faster left-hand taps in participants with higher verbal IQ values may be due to a closer cooperation of right-hemispheric regions in information processing and an intimate relationship between language and finger-motor functions. Secondary objectives assessed by explorative data analyses included gender differences and hand-eye preference. While in the females left-hand taps correlated somewhat more with verbal IQ values, in the males this effect was seen in selected variables of the right-hand taps. Moreover, laterality assessed in finger-tapping performances may not be in accordance with laterality found in the handedness questionnaire. In addition to this, congruent hand-eye dominance was found to be slightly more prevalent in participants with best verbal IQ values. However, these findings will have to be confirmed in further experiments.


Full-length ADAMTS-1 and the ADAMTS-1 fragments display pro- and antimetastatic activity, respectively.
The exact role of a disintegrin and metalloproteinase with thrombospondin motifs-1 (ADAMTS-1) and the underlying mechanism of its involvement in tumor metastasis have not been established. We have now demonstrated that overexpression of ADAMTS-1 promotes pulmonary metastasis of TA3 mammary carcinoma and Lewis lung carcinoma cells and that a proteinase-dead mutant of ADAMTS-1 (ADAMTS-1E/Q) inhibits their metastasis, indicating that the prometastatic activity of ADAMTS-1 requires its metalloproteinase activity. Overexpression of ADAMTS-1 in these cells promoted tumor angiogenesis and invasion, shedding of the transmembrane precursors of heparin-binding epidermal growth factor (EGF) and amphiregulin (AR), and activation of the EGF receptor and ErbB-2, while overexpression of ADAMTS-1E/Q inhibited these events. Furthermore, we found that ADAMTS-1 undergoes auto-proteolytic cleavage to generate the NH(2)- and COOH-terminal cleavage fragments containing at least one thrombospondin-type-I-like motif and that overexpression of the NH(2)-terminal ADAMTS-1 fragment and the COOH-terminal ADAMTS-1 fragment can inhibit pulmonary tumor metastasis. These fragments also inhibited Erk1/2 kinase activation induced by soluble heparin-binding EGF and AR. Taken together, our results suggest that the proteolytic status of ADAMTS-1 determines its effect on tumor metastasis, and that the ADAMTS-1E/Q and the ADAMTS-1 fragments likely inhibit tumor metastasis by negatively regulating the availability and activity of soluble heparin-binding EGF and AR.


The effects of diabetes with hyperlipidemia on P450 expression in APA hamster livers.
The effect of chronic hyperglycemia and hyperlipidemia induced by streptozotocin (SZ) on the expression of P450 in the liver of APA hamsters was studied in this experiment. No effect on the total activity of P450 was seen in SZ-induced diabetic hamsters throughout the experimental period. At 1 and 6 months after SZ-injection, the levels of CYP1A, 2C6, and 3A of SZ-injected hamsters were much lower than those of age-matched control hamsters. CYP2B expression tended to decrease and CYP2E1 and 4A expression tended to increase in SZ-injected hamsters, although the results were not significant. At 3 months after SZ-injection, however, no significant difference between SZ-injected and normal hamsters was seen in these P450 isozymes. On the other hand, CYP2C11 expression was slightly depressed in SZ1M and SZ6M, and almost equivalent to control hamsters in SZ3M. Immunohistochemistry by the use of each isozyme antibody revealed that SZ-induced diabetes affected the localization of CYP2C6, 3A, and 4A in the hepatic acinus. The expression of CYP2C6 and 3A was depressed mainly in the periportal region of the acinus, and CYP4A expression was induced mainly in the perivenous region by SZ-induced diabetes. On the other hand, the expression pattern of CYP1A, 2B, 2C11, and 2E1 were not affected. These results demonstrate that the effects of SZ-induced diabetes on hepatic P450 differ for each isozyme in APA hamsters and also differ from those of other experimental diabetic animals, including golden hamsters.


Molecular Mechanism of Sevoflurane Preconditioning Based on Whole-transcriptome Sequencing of Lipopolysaccharide-induced Cardiac Dysfunction in Mice.
Sevoflurane, a widely used inhalation anesthetic, has been shown to be cardioprotective in individuals with sepsis and myocardial dysfunction. However, the exact mechanism has not been completely explained. In this study, we performed whole-transcriptome profile analysis in the myocardium of lipopolysaccharide-induced septic mice after sevoflurane pretreatment. RNA transcriptome sequencing showed that 97 protein coding RNAs (mRNAs), 64 long noncoding RNAs (lncRNAs), and 27 microRNAs (miRNAs) were differentially expressed between the lipopolysaccharide and S_L groups. Functional enrichment analysis revealed that target genes for the differentially expressed mRNAs between the 2 groups participated in protein processing in the endoplasmic reticulum, antigen processing and presentation, and the mitogen-activated protein kinase signaling pathway. The bioinformatics study of differentially expressed mRNAs revealed that 13 key genes including Hsph1, Otud1, Manf, Gbp2b, Stip1, Gbp3, Hspa1b, Aff3, Med12, Kdm4a, Gatad1, Cdkn1a, and Ppp1r16b are related to the heart or inflammation. Furthermore, the competing endogenous RNA network revealed that 3 of the 13 key genes established the lncRNA-miRNA-mRNA network (ENSMUST00000192774 --- mmu-miR-7a-5p --- Hspa1b, TCONS_00188587 --- mmu-miR-204-3p --- Aff3 and ENSMUST00000138273 --- mmu-miR-1954 --- Ppp1r16b) may be associated with cardioprotection in septic mice. In general, the findings identified 11 potential essential genes (Hsph1, Otud1, Manf, Gbp2b, Stip1, Gbp3, Hspa1b, Aff3, Med12, Kdm4a, Gatad1, Cdkn1a, and Ppp1r16b) and mitogen-activated protein kinase signaling pathway involved in sevoflurane-induced cardioprotection in septic mice. In particular, sevoflurane may prevent myocardial injury by regulating the lncRNA-miRNA-mRNA network, including (ENSMUST00000192774-mmu-miR-7a-5p-Hspa1b, TCONS_00188587-mmu-miR-204-3p-Aff3, and ENSMUST00000138273-mmu-miR-1954-Ppp1r16b networks), which may be a novel mechanism of sevoflurane-induced cardioprotection.


High-performance affinity chromatography with immobilization of protein A and L-histidine on molded monolith.
Reactive monoliths of macroporous poly(glycidyl methacrylate-co-ethylene dimethacrylate) have been prepared by "in-situ" copolymerization of the monomers in the presence of porogenic diluents. Protein A and L-histidine were immobilized on the monoliths directly or through a spacer arm, respectively. The properties of these two kinds of affinity columns were characterized, and the results showed that the columns with coupling of ligands by a spacer arm have some extent of non-specific adsorption for bovine serum albumin. The affinity column based on the monolithic polymer support provided us with good hydrodynamic characteristic, low flow resistance, and easy preparation. These two affinity columns were used for the purification of immunoglobulin G from human serum. The purity of the purified IgG was detected by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The stability of the protein A affinity column was investigated, and its performance remained invariable after half a year. The effects of the nature and the pH of the buffer system on the adsorption capacity of human IgG on histidyl affinity column were also investigated. The protein A affinity column is favorable for rapid analysis of human IgG samples. In contrast, the advantages of mild elution conditions, high stability, as well as low cost provide the histidyl column further potential possibility for fast removal of IgG from human plasma in clinical applications.


Protection against type 1 diabetes upon Coxsackievirus B4 infection and iNKT-cell stimulation: role of suppressive macrophages.
Invariant natural killer T (iNKT) cells belong to the innate immune system and exercise a dual role as potent regulators of autoimmunity and participate in responses against different pathogens. They have been shown to prevent type 1 diabetes development and to promote antiviral responses. Many studies in the implication of environmental factors on the etiology of type 1 diabetes have suggested a link between enteroviral infections and the development of this disease. This study of the pancreatropic enterovirus Coxsackievirus B4 (CVB4) shows that although infection accelerated type 1 diabetes development in a subset of proinsulin 2-deficient NOD mice, the activation of iNKT cells by a specific agonist, α-galactosylceramide, at the time of infection inhibited the disease. Diabetes development was associated with the infiltration of pancreatic islets by inflammatory macrophages, producing high levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α and activation of anti-islet T cells. On the contrary, macrophages infiltrating the islets after CVB4 infection and iNKT-cell stimulation expressed a number of suppressive enzymes, among which indoleamine 2,3-dioxygenase was sufficient to inhibit anti-islet T-cell response and to prevent diabetes. This study highlights the critical interaction between virus and the immune system in the acceleration or prevention of type 1 diabetes.


Photoinduced coupled charge and proton transfers in gradually twisted phenol-pyridinium biaryl series.
A detailed photophysical analysis of a phenol-pyridinium biphenyl series with gradual twisted geometry is presented in this paper. The low-energy CT absorption band of the compounds undergoes a decrease of intensity with a progressive blue shift by increasing the twist angle of the central bond (Theta(AD)). These effects are well described and quantified within the framework of the Mulliken-Murrel approach, which allows us to extend such a model to the charge-shift process. The biaryl compounds exhibit broadened fluorescence bands assigned to the radiative deactivation of a charge shift (CSh) species generated by an intramolecular twisting relaxation of the locally excited (LE) state. Parallel to the rotamerism of the central single bond, excited-state proton-transfer (ESPT) processes are occurring from both excited states and lead to the nonemissive phenolate forms. Solvatochromic shifts of the emission bands are correlated by the Kamlet-Taft parameters (pi*, alpha, and beta). The correlation first confirms the pi* dependence of the CSh band shift but also demonstrates a clear beta dependence. The contribution of the latter parameter to the band hypsochromy is markedly increasing with Theta(AD). Such an unusual effect was ascribed to a much higher ESPT rate relative to the highly twisted conformation with respect to that of more planar geometry. Despite the suppression of the geometrical relaxation in ethanol glass at 77 K, the fluorescence of the phenolate species produced by ESPT from LE state is detected. The relative increase of its fluorescence band intensity with Theta(AD) confirms the gradual enhancement of the excited states acidity.


ROCK inhibition stimulates SOX9/Smad3-dependent COL2A1 expression in inner meniscus cells.
Proper functioning of the meniscus depends on the composition and organization of its fibrocartilaginous extracellular matrix. We previously demonstrated that the avascular inner meniscus has a more chondrocytic phenotype compared with the outer meniscus. Inhibition of the Rho family GTPase ROCK, the major regulator of the actin cytoskeleton, stimulates the chondrogenic transcription factor Sry-type HMG box (SOX) 9-dependent α1(II) collagen (COL2A1) expression in inner meniscus cells. However, the crosstalk between ROCK inhibition, SOX9, and other transcription modulators on COL2A1 upregulation remains unclear in meniscus cells. The aim of this study was to investigate the role of SOX9-related transcriptional complex on COL2A1 expression under the inhibition of ROCK in human meniscus cells. Human inner and outer meniscus cells were prepared from macroscopically intact lateral menisci. Cells were cultured in the presence or absence of ROCK inhibitor (ROCKi, Y27632). Gene expression, collagen synthesis, and nuclear translocation of SOX9 and Smad2/3 were analyzed. Treatment of ROCKi increased the ratio of type I/II collagen double positive cells derived from the inner meniscus. In real-time PCR analyses, expression of SOX9 and COL2A1 genes was stimulated by ROCKi treatment in inner meniscus cells. ROCKi treatment also induced nuclear translocation of SOX9 and phosphorylated Smad2/3 in immunohistological analyses. Complex formation between SOX9 and Smad3 was increased by ROCKi treatment in inner meniscus cells. Chromatin immunoprecipitation analyses revealed that association between SOX9/Smad3 transcriptional complex with the COL2A1 enhancer region was increased by ROCKi treatment. This study demonstrated that ROCK inhibition stimulated SOX9/Smad3-dependent COL2A1 expression through the immediate nuclear translocation of Smad3 in inner meniscus cells. Our results suggest that ROCK inhibition can stimulates type II collagen synthesis through the cooperative activation of Smad3 in inner meniscus cells. ROCKi treatment may be useful to promote the fibrochondrocytic healing of the injured inner meniscus.


Diabetes promotes DMH-induced colorectal cancer by increasing the activity of glycolytic enzymes in rats.
The objective of the present study was to investigate the association between diabetes mellitus and colorectal carcinogenesis as well as the possible mechanism involved in this interaction. Diabetes rat models were induced with a low dose of STZ followed by a low dose of DMH to induce colorectal cancer. The formation of ACF in the colon and the incidence, number and size of tumors were measured. The activity of glycolytic enzymes in colonic tissues was also measured. The results demonstrated that both the total number of ACF and the number of foci that contain a different number of crypts were increased in diabetic rats. At the end of the experimental treatment, the incidence, number and size of tumors were also increased in diabetic rats. Overall, these data indicated that diabetes increased the risk of colorectal cancer. The activity of HK and PK in colonic tissues was increased in diabetic rats, whereas the activity of PDH was decreased. In addition, the activities of these enzymes in intratumor were higher than that of in peritumor. These data indicated that the high rate of glycolysis may play a role in colorectal carcinogenesis in diabetic rats.


Role of the sintering temperature and doping level in the structural and spectral properties of Eu-doped nanocrystalline YVO4.
A sol-gel approach was employed to prepare nanosized YVO(4) nanopowders doped with Eu(3+) ions. Raw nanomaterials were thermally treated at 700-1000 °C for 3 h. X-ray diffraction (XRD) analysis demonstrated that single-phase nanopowders with high crystallite dispersion were obtained. Our studies were focused on relating the luminescence properties of the Eu(3+) dopant to the nanocrystallite (NC) size. Depending on the thermal treatment, the average NC size was calculated to range from 20 nm to 1.1 μm. We have found that the size effect manifests mainly in the expansion of the cell volume and broadening of XRD peaks, as indicated by Rietveld analysis. Moreover, emission and excitation spectra, although typical for the Eu(3+) ions, demonstrated some degree of correlation with the calcination temperature and doping concentration. To explain these differences a detailed analysis of the luminescence spectra by the Judd-Ofelt theory has been performed.


INFLAMMATORY BOWEL DISEASE: OUTPATIENT TREATMENT PROFILE.
Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease. The incidence and prevalence of both conditions have increased and are progressively increasing. These diseases are frequently recurrent and clinically highly severe. In Brazil, the lack of epidemiological data related to such diseases has left these patients in a vulnerable state and contributed to increased morbidity. To describe the profiles of patients with inflammatory bowel disease treated in an outpatient service in Brazil. This descriptive, exploratory, and retrospective documentary study with a quantitative approach was performed in an outpatient treatment service for inflammatory bowel disease, at a university polyclinic located in Rio de Janeiro, Brazil, from May to July 2016. The study included 556 patients and was approved by the research ethics committee of the institution (CAAE no. 55179316.6.0000.5259/2016). The data showed a high prevalence of inflammatory bowel disease in white female patients. Crohn's disease was diagnosed in more patients than was ulcerative colitis; the ileocolon was the most commonly affected location in patients with Crohn's disease. The stenotic phenotype was prevalent in patients with Crohn's disease. The prevalence of the stenotic phenotype in Crohn's disease in relation to others demonstrates the need for further investigations in this field of study in Brazil. In conclusion, the data showed that the epidemiologic profile of the study population is similar to that published in the national and international literature.


Transmission and damage-threshold measurements in AgGaSe(2) at 2.1 microm.
Measurements of transmission loss coefficients in AgGaSe(2) at 2.1 microm ranged from 0.012 to 0.072 cm(-1). Energy density, not peak-power density, proved to be the determining factor in AgGaSe(2) damage threshold. Coated-surface damage thresholds originally were found to be in the 1.1-2.5-J/cm(2) region by using 180-nsec laser pulses, but damage thresholds as high as 3.5 J/cm(2), with a 3 J/cm(2) average, were measured in coated samples with improved surface quality.


NDUFS4 promotes tumor progression and predicts prognosis in gastric cancer.
Gastric cancer ranked third worldwide in terms of mortality. The immediate priority is to search for new prognosticative or therapeutic targets. This research aims to examine the function of the NADH:ubiquinone oxidoreductase subunit S4 (NDUFS4) in the malignant phenotype of gastric carcinoma. We analyzed the correlation between NDUFS4 expression and gastric cancer via bioinformatics analysis and cancer tissue microarray via immunohistochemistry. Also, we detected the phenotype change in gastric cancer cells after NDUFS4 was downregulated. NDUFS4's high expression in gastric cancer tissues showed an association with terminal TNM stage and unfavorable survival. Furthermore, downregulation of NDUFS4 decreased gastric cancer cell proliferation, migration and invasion. Nude mouse models revealed that NDUFS4 promotes tumor growth. This investigation highlights the prognostic role of NDUFS4 in gastric cancer. Our results also creatively ascertained NDUFS4 as a candidate for gastric cancer therapeutic targets.


Identification of residues linked to the slow-->fast transition of thrombin.
Residues energetically linked to the allosteric transition of thrombin from its anticoagulant slow form to the procoagulant fast form have been identified by site-directed mutagenesis. The energetics of recognition by the two forms of the enzyme were probed by using a synthetic chromogenic substrate, fibrinogen, and hirudin. The thrombin residues E39, W60d, E192, D221, and D222 are linked to the slow-->fast transition and are part of an "allosteric core" through which events originating at the Na+ binding loop propagate to other regions of the enzyme. The thrombin residues Y76, W96, W148, and R173 lie at the periphery of the allosteric core, affect recognition of fibrinogen and hirudin to the same extent in both forms, and are not linked to the slow-->fast transition.


A history of neurosurgical capabilities in the United States Pacific Command: from World War II to present.
Neurosurgery has benefited from innovations as a result of military conflict. The volume and complexity of injuries sustained on the battlefield require medical teams to triage, innovate, and practice beyond their capabilities in order to treat wartime injuries. The neurosurgeons who practiced in the Pacific Command (PACOM) during World War II, the Korean War, and the War in Vietnam built upon field operating room knowledge and influenced the logistics of treating battle-injured patients in far-forward environments. Modern-day battles are held on new terrain, and the military neurosurgeon must adapt. War in the PACOM uniquely presented significant obstacles due to geographic isolation, ultimately accelerating the growth and adaptability of military neurosurgery and medical evacuation. The advancements in infrastructure and resource mobilization made during PACOM conflicts continue to inform modern-day practices and provide insight for future conflicts. In this historical article, the authors review the development and evolution of neurosurgical care, forward surgical teams, and mobile field hospitals with surgical capabilities through US conflicts in the PACOM.


On the accuracy of models for predicting sound propagation in fitted rooms.
The objective of this article is to make a contribution to the evaluation of the accuracy and applicability of models for predicting the sound propagation in fitted rooms such as factories, classrooms, and offices. The models studied are 1:50 scale models; the method-of-image models of Jovicic, Lindqvist, Hodgson, Kurze, and of Lemire and Nicolas; the emprical formula of Friberg; and Ondet and Barbry's ray-tracing model. Sound propagation predictions by the analytic models are compared with the results of sound propagation measurements in a 1:50 scale model and in a warehouse, both containing various densities of approximately isotropically distributed, rectangular-parallelepipedic fittings. The results indicate that the models of Friberg and of Lemire and Nicolas are fundamentally incorrect. While more generally applicable versions exist, the versions of the models of Jovicic and Kurze studied here are found to be of limited applicability since they ignore vertical-wall reflections. The Hodgson and Lindqvist models appear to be accurate in certain limited cases. This preliminary study found the ray-tracing model of Ondet and Barbry to be the most accurate of all the cases studied. Furthermore, it has the necessary flexibility with respect to room geometry, surface-absorption distribution, and fitting distribution. It appears to be the model with the greatest applicability to fitted-room sound propagation prediction.


Studies on mosquito larvicidal properties of Eucalyptus citriodora Hook (family-Myrtaceae).
Hexane extract obtained from leaves of Eucalyptus citriodora Hook was tested against larvae of Anopheles stephensi Liston, Culex quinquefasciatus Say and Aedes aegypti Linn to assess its toxicity and growth inhibiting activity. The results showed better activity of hexane extract against larvae of An. stephensi Liston as compared to the larvae of Cx. quinquefasciatus Say and Ae. aegypti Linn. The LC50 values against IVth instar larvae of three species were 69.86, 81.12 & 91.76 ppm respectively after 24 hours and 26.7, 29.9 & 38.8 ppm respectively after 72 hours. At lowest concentration viz. 10 ppm, 73% larvae of An. stephensi Liston failed to emergence as adult mosquito while in Cx. quinquefasciatus Say and Ae. aegypti Linn only 10 & 6% larvae failed to emerge. Further observations showed some morphological abnormalities in same pupae which could not moult normally. These results clearly indicated growth inhibition effect of the hexane extract of Eucalyptus against mosquito larvae, particularly Anopheles species. Thus Eucalyptus citriodora Hook, which is commonly found in Northern India, has a great potential for the development of an eco-friendly herbal insecticidal product for control of mosquito breeding.


Predictors of outcome for patients with COPD requiring invasive mechanical ventilation.
Accurate outcomes data and predictors of outcomes are fundamental to the effective care of patients with COPD and in guiding them and their families through end-of-life decisions. We conducted a retrospective cohort study of 166 patients using prospectively gathered data in patients with COPD who required mechanical ventilation for acute respiratory failure of diverse etiologies. The in-hospital mortality rate for the entire cohort was 28% but fell to 12% for patients with a COPD exacerbation and without a comorbid illness. Univariate analysis showed a higher mortality rate among those patients who required > 72 h of mechanical ventilation (37% vs 16%; p < 0.01), those without previous episodes of mechanical ventilation (33% vs 11%; p < 0.01), and those with a failed extubation attempt (36% vs 7%; p = 0.0001). With multiple logistical regression, higher acute physiology score measured 6 h after the onset of mechanical ventilation, presence of malignancy, presence of APACHE (acute physiology and chronic health evaluation) II-associated comorbidity, and the need for mechanical ventilation > or = 72 h were independent predictors of poor outcome. We conclude that among variables available within the first 6 h of mechanical ventilation, the presence of comorbidity and a measure of the severity of the acute illness are predictors of in-hospital mortality among patients with COPD and acute respiratory failure. The occurrence of extubation failure or the need for mechanical ventilation beyond 72 h also portends a worse prognosis.


Cardiac apoptosis: from organ failure to allograft rejection.
Cardiac myocyte apoptosis has been extensively studied in the last few years. Increased interest in the field stems from the hope that pharmacological manipulation of apoptosis may become a valuable tool for preventing excessive cell death observed in different pathological conditions. This paper is not intended as a comprehensive overview of current research about life and death in the cardiovascular system, but rather as a concise update on new developments in areas that were highlighted in a recent series of excellent reviews. A short inventory of unsolved issues concerning the significance of cardiac myocyte loss through apoptosis in both physiological and pathological circumstances is addressed.


Role of phylogenetically conserved amino acids in folding of Na,K-ATPase.
This paper focuses on the amino acid sequence 708-TGDGVNDSPALKK in pig kidney Na,K-ATPase as one of the best conserved among P-type ATPases. In Ca-ATPase this sequence forms a strand-loop-helix structure as part of a Rossman fold next to the phosphorylation site. Substitution of polar residues in the investigated sequence interfered with high-level accumulation of mutant protein. Mutant alpha1-subunit protein only accumulated in membranes from yeast cells grown at 15 degrees C whereas wild-type protein accumulated at both 15 and 35 degrees C. A systematic screen for the molecular mechanism behind lack of accumulation of mutant protein at 35 degrees C showed that transcription and translation were unaffected by the mutations. To demonstrate in vivo protein folding problems, an unfolded protein response reporter system was constructed in yeast. In this strain, only expression of mutant Na,K-ATPase alpha1-subunit caused induction of the unfolded protein response at 35 degrees C, indicating folding problems in the ER. Lowering the expression temperature to 15 degrees C prevented induction of the unfolded protein response after mutant protein expression, indicating correct folding at this temperature. At the permissive temperature mutant proteins were able to escape the endoplasmic reticulum quality control, reach the plasma membrane, and bind ouabain with high affinity. Since mutants in the 708-TGDGVNDSPALKK segment had a thermo inactivation profile identical to that of wild type, they were classified as temperature-sensitive synthesis mutants. The results indicate that this segment contributes side chains of importance for overall folding and maturation of Na,K-ATPase and all other P-type ATPases.


A content analysis of internet information sources on medical cannabis.
Medical cannabis users report that their knowledge regarding cannabis is predominantly from their own personal experiences and the Internet. We summarize and describe information found through Internet searches on medical cannabis in English language websites. We used terms related to medical cannabis in the Google search engine between November and December 2019. Resulting websites were catalogued and coded for content, including mentions of health and medical conditions, pharmacology, dosage, harmful or adverse effects, harm reduction techniques, cautions or warnings, products for sale, and credentials. We coded 344 web pages on 179 unique websites. Cannabis was mentioned for the treatment of 151 different medical and health conditions, only four of the twenty most frequently mentioned conditions have received substantial empirical support for cannabis or cannabinoid treatment. Information content varied widely across sites, only a small proportion of sites included information on pharmacology, dosage, risks, and other aspects that are requirements for pharmaceutical drugs. Information provided was only moderately related to conclusions in the emerging scientific literature. Given the rise in cannabis use within the U.S. and the reliance on the Internet as a source of information, considerable efforts are needed to provide accurate on-line cannabis education to minimize harms and maximize benefits for individuals and society.


The tetrameric molecule of conventional kinesin contains identical light chains.
Conventional kinesin is a multifunctional motor protein that transports numerous organelles along microtubules. The specificity of kinesin-cargo binding is thought to depend on the type(s) of light chains that a kinesin molecule contains. We have shown previously that different isoforms of kinesin light chains are associated with different types of cargo, mitochondria and membranes of the Golgi complex. Here, we provide evidence that the two light chains present within each kinesin molecule are always of the same type. Further, we demonstrate that kinesin heavy chains interact with nascent light-chain polypeptides on ribosomes. These data suggest that incorporation of the two identical light chains into a single kinesin molecule most likely occurs cotranslationally.


Correlation between Chronological Age, Dental Age and Skeletal Age among Monozygoyic and Dizygotic Twins.
Chronological age, dental development, height and weight measurements, sexual maturation characteristics and skeletal age are some biological indicators that have been used to identify time of growth. Many researchers have agreed that skeletal maturity is closely related to the craniofacial growth, and bones of hand and wrist are reliable parameters in assessing it. The complete hand and wrist radiograph involves 30 bones and assessment of these bones is one elaborate task. The present study is therefore, undertaken to assess the correlation between the chronological age, dental age and skeletal ages among different types of twins. The study consisted of 60 subjects (30 twins) aged 8 to 16 years, divided into group of 10 monozygotic, 10 dizygotic and 10 mixed sex twins. The sample was selected from Twin Survey- 2008 conducted by Department of Orthodontics and Dentofacial Orthopaedics, Sree Balaji Dental College and Hospital, Chennai. Their zygosity was determined by sex, blood groups and by the parent. The chronological age was measured by the date of birth given by the parents. Panoramic and hand wrist x-rays were taken. Dental age was assessed by Demerjian et al method and skeletal age by Greulich and Pyle method. The correlation among twins in dental and skeletal ages with the chronological age was assessed using Correlation Coefficient and Student's't' Test. The obtained data was fed into the computer and statistical analysis was done for the same using the SPSS version 10.0. Statistical significance was tested at P<0.05 level. Mean and Standard Deviation, Correlation Coefficient, Student's't' Test statistical methods were employed. The result showed highly significant 'p' value as <0.001 in all the correlations except for mixed pairs. Descriptive statistics in most of the areas demonstrated a non-significant result between zygosity groups. There is a correlation existing between the individual's chronological age, dental age and skeletal age and correlation also exists in the twin pairs of the same zygosity and among each pair but no correlation exists between different zygotic twins. How to cite this article: Gupta M, Divyashree R, Abhilash P R, Bijle M N A, Murali K V. Correlation between Chronological Age, Dental Age and Skeletal Age among Monozygoyic and Dizygotic Twins. J Int Oral Health 2013; 3(1):16-22.


Noninvasive haemodynamic monitoring using finger arterial pressure waveforms.
Haemodynamic monitoring may potentially lead to improved quality of care in haemodynamic compromised patients. However, the usefulness of invasive techniques using the pulmonary artery catheter is questioned. Noninvasive techniques which provide data on haemodynamics might provide a good alternative. New techniques have been developed in recent years to monitor cardiac output and other parameters of cardiac performance continuously and noninvasively. Recently, a new technique has become available that assesses these haemodynamic data from finger arterial pressure waveforms obtained noninvasively. Although an invasively derived calibration is still needed to obtain absolute data on cardiac output, relative changes in cardiac output can be accurately monitored using this method. Currently, the device can be used in patients to continuously monitor haemodynamic data and guide therapy. Furthermore, it might have a role in clinical research to noninvasively assess cardiac output, as a surrogate endpoint, before and after interventions. Although this new method seems promising, the clinical value has to be proven.


Emotional distress and cognitive functioning of older couples: a dyadic analysis.
This article examines the relationship between cognitive functioning and emotional distress in a sample of 2,684 married couples from the 2006 and 2008 Korean Longitudinal Study of Aging. Using the Center for Epidemiologic Studies Depression (CESD) scale and the Mini-Mental State Exam (MMSE), we analyze the interrelation between emotional and cognitive health for individuals and spouses with with dyadic regression models. We test how emotional distress and cognitive impairment affect each other within individuals and from one spouse to another. We find emotional distress contributes to cognitive impairment for wives but not for husbands. We also find emotional distress and cognitive impairment in one spouse affects that in the other. We find no evidence that emotional distress effects spouse's cognitive impairment or that the cognitive ability impacts spouses' emotional distress. We discuss the results within the context of existing literature, focusing on the socioeconomic and clinical factors that explain these interrelations.


Penetrating bladder trauma: a high risk factor for associated rectal injury.
Demographics and mechanisms were analyzed in prospectively maintained level one trauma center database 1990-2012. Among 2,693 trauma laparotomies, 113 (4.1%) presented bladder lesions; 51.3% with penetrating injuries (n = 58); 41.3% (n = 24) with rectal injuries, males corresponding to 95.8%, mean age 29.8 years; 79.1% with gunshot wounds and 20.9% with impalement; 91.6% arriving the emergence room awake (Glasgow 14-15), hemodynamically stable (average systolic blood pressure 119.5 mmHg); 95.8% with macroscopic hematuria; and 100% with penetrating stigmata. Physical exam was not sensitive for rectal injuries, showing only 25% positivity in patients. While 60% of intraperitoneal bladder injuries were surgically repaired, extraperitoneal ones were mainly repaired using Foley catheter alone (87.6%). Rectal injuries, intraperitoneal in 66.6% of the cases and AAST-OIS grade II in 45.8%, were treated with primary suture plus protective colostomy; 8.3% were sigmoid injuries, and 70.8% of all injuries had a minimum stool spillage. Mean injury severity score was 19; mean length of stay 10 days; 20% of complications with no death. Concomitant rectal injuries were not a determinant prognosis factor. Penetrating bladder injuries are highly associated with rectal injuries (41.3%). Heme-negative rectal examination should not preclude proctoscopy and eventually rectal surgical exploration (only 25% sensitivity).


How researchers define vulnerable populations in HIV/AIDS clinical trials.
In this study, we interviewed researchers, asking them to define vulnerable populations in HIV/AIDS clinical trials, and provide feedback on the federal regulations for three vulnerable populations. Interview data informed a conceptual framework, and were content analyzed to identify acceptability or disagreement with the regulations. Beginning with several characteristics of vulnerable enrollees identified by researchers, the conceptual framework illustrates possible scenarios of how enrollees could be considered vulnerable in clinical research. Content analysis identified barriers affecting HIV/AIDS researchers' ability to conduct clinical trials with pregnant women, prisoners, and children, for which the regulations specify additional protections. This study challenges current thinking about federal regulations' group-based approach to defining vulnerable populations.


Carotid surgical cut-down technique for neuroendovascular therapy.
Neuroendovascular therapy is typically performed via the femoral artery, but there are rare cases in which a tortuous upstream angioarchitecture makes it difficult to access the intracranial circulation via this route. In this case series, we describe six cases treated by surgical cut-down in the neck, with puncture of the carotid artery. Antiplatelet and anticoagulation agents were used in all cases. The indications for the technique were postsurgical thoracic aortic aneurysm (two cases), postsurgical abdominal aortic aneurysm (one case), major vessel tortuosity of the common carotid artery (two cases) and aortic arch anomaly (one case). The surgical cut-down technique permitted successful neuroendovascular therapy. Although one patient had a small cervical haematoma, he was treated without surgical evacuation. Overall, our findings indicate that the surgical cut-down technique is safe and useful for patients in whom the femoral approach is unsuitable.


Clinical neuroimaging in psychiatry.
The practical aspects of contemporary neuroimaging techniques relevant to clinical psychiatry are reviewed. In particular, the structural imaging modalities of computed axial tomography (CT) and magnetic resonance imaging (MRI) are described and compared. Likewise, functional neuroimaging modalities including the nuclear imaging techniques of positron emission tomography (PET) and single photon emission computed tomography (SPECT), as well as the newer magnetic resonance techniques of functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS), are reviewed. Although structural imaging techniques are most useful for ruling out medical etiologies of mental status disturbances, functional neuroimaging techniques currently have an adjunctive role in the evaluation of dementia and seizure disorders and show promise for the evaluation of primary psychiatric disorders in the future. Specific guidelines are suggested regarding the use of these neuroimaging studies.


Incidence of DVT following surgery of the foot and ankle.
A prospective study was undertaken to establish the incidence of deep vein thrombosis (DVT) in patients who had undergone surgery of the foot and ankle. All consecutive patients who underwent foot and ankle surgery in the senior author's practice had duplex ultrasound performed of the bilateral calves at the first postoperative visit. Of 201 patients, deep calf clots were found in seven patients (3.5%), but none of these showed progression on follow-up ultrasound or extension proximal to the calf. By the authors' criteria, none of the studied patients required treatment. The authors feel that the rate and progression of DVT after foot and ankle surgery is low and does not require routine prophylaxis. Factors associated with risk of DVT formation were postoperative immobilization, hindfoot surgery, tourniquet time and advancing age.


[Professional containment methods used in psychiatry wards: justifications for their utilization, types, international practices, and perceptions].
The aim of this review is to examine the literature on professional containment methods, to draw attention to this important topic concerning which relevant research remains limited in our country and to offer professionals the opportunity to make evaluations utilizing holistic perspectives. Relevant, obtainable studies published within the last 15 years, but primarily after the year 2000, were included in this retrospective literature review. For this purpose a literature search was conducted via-internet based search engines, including Pubmed, Science Direct, Medline, Psychinfo, the ULAKBIM Turkish Medicine Index and the Turkish Psychiatry Index, using the keywords containment methods, psychiatry, aggression, conflict, restraint, seclusion and mental health hospitals, in different combinations. According to the literature, professional containment methods are defined as methods used to prevent harm to patients or others as a result of the patient's conflict-provoking behaviour (aggression, absconding, rule breaking, refusing medication etc.) in psychiatric wards. These methods include the use of mechanical/physical restraint, seclusion, compulsory intramuscular sedation, observation, and pro re nata (prn) medication. The type and frequency of use, views or attitudes to methods varies between different countries. Although professional containment methods are an effective management strategy, they may cause physical and psychological damage to both patient and staff. So the use of these methods in psychiatric care settings remains controversial and an ongoing source of legal and ethical dilemmas. Despite discussions, the containment methods used in the past remain present as a part of psychiatric treatment and care. There is a need for standard practice guidelines to ensure the security of patients and staff and to use those methods effectively and correctly. In conclusion, it is necessary that health care professionals be informed about preparing the new guidelines and using professional containment methods effectively.


A Three-Membered Diazo-Aluminum Heterocycle to Access an Al=C π Bonding Species.
[1+2] cycloaddition between a cyclic (alkyl)(amino)aluminyl anion (3) and diaryldiazomethane affords an AlN2 three-membered ring species (4). Compound (4) is thermally unstable and spontaneously releases N2 gas under the mild reaction condition to generate an ion-separated species 5. An X-ray study shows that the anionic part of 5 bears a considerable short exocyclic Al-C bond, and computational studies involving molecular orbital and natural bond orbital analysis indicate the Al=C π bonding character. The Al=C moiety of 5 undergoes intramolecular C-H activation. Moreover, reaction of 5 with a diazo compound leads to the reduction and complete cleavage of the N=N double bond.


Methodological, ethical, and legal considerations in drug court research.
Since their inception in the late 1980s, drug courts have become the most prevalent specialty court in the United States. A large body of outcome research conducted over the past two decades has demonstrated that drug courts effectively reduce drug use and criminal recidivism, which has led to the rapid proliferation of these courts. Importantly, drug court research has flourished despite the many challenges faced by researchers when working with a vulnerable population of justice-involved substance users. In this article, we highlight the most common methodological, ethical, and legal challenges encountered in drug court research, and discuss ways in which researchers can overcome these challenges to conduct high-quality research. Drug court research exemplifies how rigorous empirical investigation can be accomplished in the criminal justice system, and it can serve as a useful model for researchers working in other parts of the judicial system.


Perioperative supplemental oxygen therapy and surgical site infection: a meta-analysis of randomized controlled trials.
To conduct a meta-analysis of randomized controlled trials in which high inspired oxygen concentrations were compared with standard concentrations to assess the effect on the development of surgical site infections (SSIs). A systematic literature search was conducted using the MEDLINE, EMBASE, and Cochrane databases and included a manual search of references of original articles, poster presentations, and abstracts from major meetings ("gray" literature). Twenty-one of 2167 articles met the inclusion criteria. Of these, 5 randomized controlled trials (3001 patients) assessed the effect of perioperative supplemental oxygen use on the SSI rate. Studies used a treatment-inspired oxygen concentration of 80%. Maximum follow-up was 30 days. Data were abstracted by 3 independent reviewers using a standardized data collection form. Relative risks were reported using a fixed-effects model. Results were subjected to publication bias testing and sensitivity analyses. Infection rates were 12.0% in the control group and 9.0% in the hyperoxic group, with relative risk reduction of 25.3% (95% confidence interval [CI], 8.1%-40.1%) and absolute risk reduction of 3.0% (1.1%-5.3%). The overall risk ratio was 0.742 (95% CI, 0.599-0.919; P = .006). The benefit from increasing oxygen concentration was greater in colorectal-specific procedures, with a risk ratio of 0.556 (95% CI, 0.383-0.808; P = .002). Perioperative supplemental oxygen therapy exerts a significant beneficial effect in the prevention of SSIs. We recommend its use along with maintenance of normothermia, meticulous glycemic control, and preservation of intravascular volume perioperatively in the prevention of SSIs.


Paraneoplastic limbic encephalitis: diagnostic relevance of CSF analysis and total body PET scanning.
We report two cases of paraneoplastic limbic encephalitis (PLE) that differed in their clinical patterns, the underlying tumours, and the associated paraneoplastic antibodies. The first patient was a young adult male, with anti-MA-2 antibodies and testicular tumour. The clinical picture was restricted to limbic involvement. The second patient was a 56-year old, female heavy smoker; with seizures and depression, but also vertigo and diplopia. A low level of serum anti-Hu antibodies led to the detection of a small cell lung carcinoma by total body PET-scanning. In both cases, intrathecal synthesis of CSF oligoclonal IgG bands and of the corresponding paraneoplastic antibodies was demonstrated.


[Meningitis and encephalitis in Poland in 2008].
In Poland, 2 475 cases of neuroinfections were reported in 2008, of which 979 had bacterial aetiology, 1 122--viral aetiology, and 374--other or unknown origin. The etiological agent was determined in 555 (56%) cases of bacterial neuroinfections. Among them Neisseria meningitidis was found in 220 cases, Haemophilus influenzae type B (Hib) in 23 cases and Streptococcus pneumoniae in 151 cases. An increasing trend in meningococcal infections incidence has been observed in 2008, and a substantial decrease of Hib incidence, related to increasing vaccination coverage. Viral neuroinfections incidence in 2008 decreased compared to year 2007. Among confirmed cases, there were 202 cases of tick-borne encephalitis. Most of the cases were reported from endemic areas of north-eastern part of the country.


[Psychological states and personality as factors in the morbidity of head and neck malignant tumors].
Many publications have repeatedly indicated that there seems to be a correlation between neoplastic disease and certain types of psychological situations. However, such studies subjected malignant tumors in head and neck region are scanty so far. We applied Cornell Medical Index Health Questionnaire (CMI) and Maudsley Personality Inventory (MPI) to collect medical and psychiatric data from 86 patients (56 males and 30 females) with head and neck malignant tumors and 115 control patients (73 males and 42 females) with head and neck diseases other than malignant tumors. Analysis of CMI data using Diagnostic Sheet, Fukamachi's method and Modification of Abe's method, and analysis of each of Extroversion-Introversion scale scores, Neuroticism scale scores and Lie scale scores of MPI led the following conclusion. 1) Both male and female patients with head and neck malignant tumors showed to be more depressive than their control patients were. Especially, between the two patient groups in males, there was a statistically significant (p less than 0.05) difference. 2) Regarding neurosis, autonomic nerve dysfunctioning and extroversion-introversion, none of these factors seemed to be related with the morbidity of head and neck malignant tumors. Further exploration of this issue, with a special attention to the relationship between depression and head and neck malignancy should be conducted, if possibly, from a prospective point of view.