Targetability and intracellular delivery of anti-BCG antibody-modified, pH-sensitive fusogenic immunoliposomes to tumor cells.
We prepared tumor-specific immunoliposomes by coupling anti-BCG monoclonal antibodies to pH-sensitive fusogenic liposomes modified with succinylated polyglycidol (sucPG), in order to obtain efficient binding to, and endocytotic internalization into, the tumor cells. Mouse colon carcinoma 26 cells, which are known to share a common antigen with BCG, were used in in vitro experiments. BCG-sucPG immunoliposomes showed fusion ability under acidic conditions. Fluorescence microscopic observation indicated that BCG-sucPG immunoliposomes bound to colon 26 tumor cells and induced receptor-mediated endocytosis at 37 degrees C. Fusion assay by resonance energy transfer using N-(7-nitro-2-1,3-benzoxadiazol-4-yl) diacyl phosphatidylethanolamine and N-(lissamine rhodamine B sulfonyl) diacyl phosphatidylethanolamine suggested that fusion between BCG-sucPG immunoliposomes and endosomal and/or lysozomal membrane did occur. These results imply that the BCG-sucPG immunoliposomes transfer their content into the cytoplasm by fusing with the endosomal and/or lysozomal membrane after recognition of target cells and subsequent internalization into the cells by endocytosis.


Effects of mediastinal lymph node dissection in colorectal cancer-related pulmonary metastasectomy.
The benefits of mediastinal lymph node dissection (MLND) in colorectal cancer-related pulmonary metastasectomy (PM) have been poorly reported. This study aimed to determine whether MLND affects survival in patients undergoing PM and to identify the prognostic factors for survival. We retrospectively reviewed 275 patients who had undergone colorectal cancer-related PM from January 2010 to December 2016. MLND was defined as the resection of at least six mediastinal lymph node stations according to the International Association for the Study of Lung Cancer criteria (N1, ≥3 stations; N2, ≥3 stations). The propensity score matching method was used to reduce bias. Thirty-three (12%) patients underwent MLND, and 13 (4.7%) patients had mediastinal lymph node involvement. This study showed no difference in 5-year overall survival (no MLND, 52.7% vs. MLND, 53.5%; p = 0.81). On multivariable analysis, negative prognostic factors for overall survival were preoperative carcinoembryonic antigen (CEA) level (p < 0.001), a higher number of metastatic nodules (p < 0.001), metastatic nodule size ≥2 cm (p < 0.001), and lymph node involvement (p = 0.006). Mediastinal lymph node involvement, preoperative CEA level, higher metastatic nodule number, and nodule size negatively affected survival whereas MLND in PM was not associated with survival.


Crystal structures of N-[4-(tri-fluoro-meth-yl)phen-yl]benzamide and N-(4-meth-oxy-phen-yl)benz-amide at 173 K: a study of the energetics of conformational changes due to crystal packing.
As a part of our study of the syntheses of aryl amides, the crystal structures of two benzamides were determined from single-crystal X-ray data at 173 K. Both crystal structures contain mol-ecular units as asymmetric units with no solvent in the unit cells. Crystal structure I, TFMP, is the result of the crystallization of N-[4-(tri-fluoro-meth-yl)phen-yl]benzamide, C14H10F3NO. Crystal structure II, MOP, is composed of N-(4-meth-oxy-phen-yl)benzamide, C14H13NO2, units. TFMP is triclinic, space group P , consisting of two mol-ecules in the unit cell related by the center of symmetry. MOP is monoclinic, space group P21/c, consisting of four mol-ecules in the unit cell. Both types of mol-ecules contain three planar regions; a phenyl ring, an amide planar region, and a para-substituted phenyl ring. The orientations of these planar regions within the asymmetric units are compared to their predicted orientations, in isolation, from DFT calculations. The aryl rings are tilted approximately 60° with respect to each other in both experimentally determined structures, as compared to 30° in the DFT results. These conformational changes result in more favorable environments for N-H⋯O hydrogen bonding and aryl ring π-stacking in the crystal structures. Inter-molecular inter-actions were examined by Hirshfeld surface analysis and qu-anti-fied by calculating mol-ecular inter-action energies. The results of this study demonstrate that both hydrogen bonding and dispersion are essential to the side-by-side stacking of mol-ecular units in these crystal structures. Weaker dispersion inter-actions along the axial directions of the mol-ecules reveal insight into the melting mechanisms of these crystals.


Exhuming the body: revisiting the role of the visible body in ethnographic research.
Looking back is often painful. Although in the first instance I might approach a research project with enthusiasm and confidence, in retrospect the sins of omission can become very obvious. In reviewing five research projects employing qualitative ethnographic methods, I explored the underacknowledged role of the visible body in these projects. Although the task of retrospection is blessed with the accumulated wisdom of others, I emphasize the importance of ongoing self-scrutiny and critical analysis of methodological dogmas for researchers and their practices.


The TNF receptor 1: a split personality complex.
The tumor necrosis factor receptor 1 (TNFR1), a prototypic member of the death receptor family signals both cell survival and apoptosis. In this issue of Cell, report that apoptotic TNFR1 signaling proceeds via the sequential formation of two distinct complexes. Since the first complex can activate survival signals and influence the activity of the second complex, this mechanism provides a checkpoint to control the execution of apoptosis.


Evaluation of a training program for emergency medical service physician dispatchers to reduce emergency departments visits.
Emergency Departments (ED) have seen an increasing number of older patients who are mostly referred following a call to the Emergency Medical Services (EMS). Long waiting times in settings, which are not designed to meet older patients' needs, may increase the risk of hospital-acquired complications. Unnecessary visits should therefore be avoided as much as possible. The objective of the study was to evaluate whether a program to provide geriatric knowledge and tools to the dispatching physicians of the EMS could decrease ED referrals of older patients. Design: Before-and-after study with two 6-month periods before and after intervention. All calls received by a dispatching physician of the Rhône EMS from 8 am to 6 pm concerning patients aged 75 years or above during the study period. A program consisting of training dispatching physicians in the specific care of older patients and the developing, with a multidisciplinary team, of specific tools for dispatching physicians. Proportion of ED referrals of patients aged 75 years or above after a call to the EMS. A total of 2671 calls to the Rhône EMS were included corresponding to 1307 and 1364 patients in the pre-and post-intervention phases, respectively. There was no significant difference in the proportion of referrals to the ED between the pre-intervention (61.7%) and the post-intervention (62.8%) phases (p = 0.57). Contact of the patients with their General Practitioner (GP) in the month preceding the call was associated with a 22% reduced probability of being referred to an ED. No beneficial effect of the intervention was demonstrated. This strategy of intervention is probably not effective enough in such time-constraint environment. Other strategies with a specific parallel dispatching of geriatric calls by geriatricians should be tested to avoid these unnecessary ED referrals. ClinicalTrials NCT02712450.


Telephone-based behavioral activation with mental imagery for depression: A pilot randomized clinical trial in isolated older adults during the Covid-19 pandemic.
To shield vulnerable persons, particularly the elderly, during the Covid-19 pandemic governments around the world have advised to use social distancing and self-isolation. Social isolation might put older adults at an increased risk for mental health problems such as depression. There is a need for brief, easy-accessible psychological treatments for depressive symptoms that can be delivered remotely. The aim of this study was to investigate the feasibility, acceptability, and preliminary efficacy of telephone-delivered Behavioral Activation with Mental Imagery (BA-MI) for the treatment of depressive symptoms in individuals 65 years and older living in isolation during the Covid-19 pandemic. In this open-label pilot randomized clinical trial, N = 41 individuals aged 65 years or older with clinically significant symptoms of depression were randomly assigned to either a BA-MI treatment condition, or an Attention-Assessment control condition delivered over the telephone over a 4-week period. Depressive symptoms decreased more in the treatment condition compared to the control condition. At post-treatment, 2 out of 16 participants in the treatment condition met diagnostic criteria for depression compared to 9 out of 13 in the control condition. Most participants in the treatment condition were satisfied with the treatment and few adverse effects were observed. This pilot study suggests that behavioral activation with mental imagery delivered over the telephone is feasible, acceptable, and potentially efficacious for the treatment of depressive symptoms in older individuals living in isolation. Replication in larger samples is needed.


A randomized trial comparing gastric and colorectal endoscopic submucosal dissection defect closure using novel through the scope suturing system with over-the-scope suturing system.
Mucosal closure adds time but reduces complications associated with endoscopic submucosal dissection (ESD). We aim to assess the closure time, technical success and cost effectiveness between a novel through-the-scope helix tack suture system (TTSS) and the over-the-scope suturing system (OTSS). In this single center, prospective, randomized trial, all patients having ESD with anticipated closure were randomized 1:1 to TTSS (study group) or OTSS (control group.) The primary outcome was the "closure time" (CT) and "overall closure time" (OCT, CT + setup time). Secondary outcomes were rates of technical success, adverse events and cost effectiveness. 40 patients were randomized (20 each to OTSS and TTSS). OTSS and TTSS groups were similar with respect to age, gender, proportion of colorectal polyps, proximal colon polyps and mean size of resected specimen in mm (40.9 vs 40.4). The mean CT was 18.4 min for OTSS and 23.3 min for TTSS (P=0.36). The mean OCT was 32 min for OTSS and 39.5 min for TTSS (P=0.36). Closure with primary device was successful in 17 (85%) cases with OTSS and 18 (90%) cases with TTSS (P=0.63). No closure related intraprocedural complications or delayed perforations were noted. Mean cost of closure was significantly lower in TTSS groups for lesions smaller than 35 mm (P=0.008). TTSS is not superior to OTSS with respect to closure time, technical and clinical success for closure of gastric and colorectal ESD defects. TTSS is more cost effective for closure of lesions smaller than 35 mm.


Differences of drivers' reaction times according to age and mental workload.
This study was designed to examine differences in reaction times of drivers of various age groups and to assess the influence of mental workload on reaction times. Experiments were performed on a simulated street and under other conditions to identify drivers with long reaction times and drivers whose reaction times are affected strongly by mental workloads while driving on a public road. Reaction times after hearing a buzzer were measured under five conditions: (1) sitting in a stationary vehicle, (2) executing mental calculations in a stationary vehicle, (3) driving on a simulated street, (4) executing mental calculations while driving on a simulated street, and (5) driving on a public road. Subjects were 10 drivers each of three age groups. Each experiment was performed by these subjects under the five conditions. Results showed that mental calculations increased the average reaction time for each age group. Mental calculations increased differences among age groups and individuals, and increased differences in respective drivers' individual performance. Mental calculations influenced elderly drivers' reaction times remarkably. Results also demonstrated that an experiment on a simulated street identified drivers who showed long reaction times on a public road.


Manipulation for frozen shoulder: long-term results.
Although much has been published regarding shoulder manipulation under anesthesia for the treatment of frozen shoulder, there are no reported long-term results. In 25 patients (26 shoulders) in whom nonoperative treatment for idiopathic frozen shoulder had failed, we performed manipulation under anesthesia. All had had physical therapy for a mean of 6.2 months. Follow-up was by examination until the end of active treatment. Longer-term follow-up was obtained in 18 patients (19 shoulders) by questionnaire and averaged 15 years (range, 8.1 to 20.6 years). There were significant improvements in forward elevation from a mean of 104 degrees before manipulation (range, 70 degrees to 140 degrees ) to 168 degrees (range, 90 degrees to 180 degrees ) and in external rotation from 23 degrees (range, -5 degrees to 70 degrees ) to 67 degrees (range, 0 degrees to 90 degrees ). There were 16 shoulders with no pain or slight pain and 3 with occasional moderate or severe pain. There were no fractures, dislocations, or other complications. Of the 19 shoulders, 18 required no further surgery. At long-term follow-up, the mean Simple Shoulder Test score was 9.5 out of 12 and the mean American Shoulder and Elbow Surgeons score was 80 out of 100. Treatment of idiopathic frozen shoulder by manipulation under anesthesia leads to sustained improvement in shoulder motion and function at a mean of 15 years after the procedure.


How cues to social categorization impact children's inferences about social categories.
Social categorization involves two crucial processes: First, children seek properties on which they can categorize individuals, i.e., they learn to form social categories; then children make inferences based on social category membership and might develop affective responses toward social categories. Over the last decade, a growing number of research in developmental psychology started to use novel social categories to investigate how children learn and reason about social categories. To date, three types of cues have been put forward as means to form social categories, namely linguistic, visual, and behavioral cues. Based on social category membership, children draw inferences about the shared properties of social category members and about how social category members ought to behave and interact with each other. With additional input, children might apply essentialist beliefs to social categories and develop affective responses toward social categories. This article aims to provide key insights on the development of stereotypes and intergroup biases by reviewing recent works that investigated how children learn to form novel social categories and the kind of inferences they make about these novel social categories.


Oligomycin sensitivity of mitochondrial sulfhydryl groups.
Dithionitrobenzoate has been used to titrate sulfhydryl groups of rat liver mitochondria in glutamate buffer, pH 7.4. Reaction with oligomycin and different SH reagents preceded the SH titration. Under these conditions it was found that 2-mercaptopropionylcne and N-ethylmaleimide reacted in an oligomycin-sensitive manner, so that the control values (in the absence of SH reagent) were obtained. Similar concentrations of mersalyl and of N-(N-acetyl-4-sulfamoylphenyl) maleimide, in the presence of oligomycin, enhanced reactivity toward Nbs2. The concentration range of oligomycin-sensitive SH groups was thus defined between approx. 5 and 9 nmol reagent/mg mitochondrial protein. In this way, a differentiation between SH grops, which are implicated in phosphate transport antd those, which react in an oligomycin-sensitive manner, and which are probably connected with the coupling mechanism was achieved.


Variations in the structure and transcription of the mitochondrial atp and cox genes in wild Solanum species that induce male sterility in eggplant (S. melongena).
In order to determine the molecular basis of cytoplasmic male sterility (CMS) in alloplasmic lines of eggplant, the genomic structures and transcription patterns of mitochondrial ATP synthase subunit (atp) and cytochrome oxidase subunit (cox) genes were studied for wild and cultivated eggplants. Alloplasmic eggplant lines with cytoplasms of wild Solanum species showing either anther indehiscent type of CMS or non-pollen production type of CMS were studied with the cultivated eggplant Solanum melongena, used as a control. Southern hybridization of the mitochondrial genes indicated the difference between the two types of CMS and showed complete identity within each type. The cytoplasmic patterns of all wild species differed from that of the cultivated eggplant. Thus, the cytoplasm of the six wild eggplants and the one cultivated eggplant was classified into three groups. Male sterile plants of both types of CMS showed novel transcription patterns of atp1, whereas a different transcription pattern of cox2 was observed only in the anther indehiscent type. Based on these differences, we determined the DNA sequences of about a 4 kbp segment in the atp1 region. Although the coding and 3' flanking regions were almost identical among the cytoplasms, the 5' flanking region was completely different and novel open reading frames (orfs) were found for each of the CMS types and the cultivated eggplant. The cytoplasm of Solanum kurzii inducing the anther indehiscent type CMS had orf312, and those of Solanum aethiopicum and Solanum grandifolium of non-pollen production type CMS had orf218. The correspondence between the transcription patterns of these orfs and phenotypic expression of male sterility strongly suggests that these orfs are causal genes for each type of CMS.


Effect of a dedicated PI-QUAL curriculum on the assessment of prostate MRI quality.
The Prostate Imaging Quality (PI-QUAL) score is a metric to evaluate the diagnostic quality of multiparametric magnetic resonance imaging (MRI) of the prostate. This study evaluated the impact of a prostate MRI quality training lecture on the participant's ability to assess prostate MRI image quality. Eighteen in-training-radiologists of varying experience in reviewing diagnostic prostate MRI assessed the image quality of ten examinations. Then, they attended a dedicated lecture on MRI quality assessment using the PI-QUAL score. After the lecture, the same participants evaluated the image quality of a new set of ten scans applying the PI-QUAL score. Results were assessed using receiver operating characteristic (ROC) analysis. The reference standard was the PI-QUAL score assessed by a fellowship trained abdominal radiologist with experience in reading prostate MRI. There was a significant improvement in the average area under the curve (AUC) for assessment of prostate MRI image quality from baseline (0.82; [0.576 - 0.888]) to post teaching (1.0; [0.954-1]), with an improvement of 0.18 (p < 0.03). When ROC curves were computed for different cohorts stratified based on year of training, difference ranged from 0.48 for second year residents to 0.32 for fourth year residents (p < 0.001-0.01). For abdominal imaging fellows, the pre-teaching AUC was 0.9 [0.557-1] and post teaching AUC was 1 [0.957-1], a difference of 0.1 (p = 0.20). A dedicated lecture on PI-QUAL improved the ability of radiologists-in-training to assess prostate MRI image quality, with variable impact depending on year of training.


First self-perceived signs and symptoms in emerging psychosis compared with depression.
To investigate differences between the early symptoms of schizophrenia and depressive disorders. Sixty-one individuals with an at-risk mental state (ARMS), 17 of whom later made the transition to psychosis, 37 patients with a first episode of psychosis and 16 controls with depressive disorders were interviewed about first self-perceived signs and symptoms. In ARMS and first episode of psychosis, on average, first self-perceived signs or symptoms had occurred about 5-6 years before the interview. In ARMS, including transition to psychosis, 'loss of energy' and 'difficulties concentrating' were the most frequently recalled first signs. There was much overlap for the four most frequently mentioned symptoms in the three groups. As compared with ARMS, controls with depressive disorders significantly more often recalled 'depression' and 'social isolation' as the very first signs of disease. Clinicians should consider the development of self-recalled first signs over time carefully when assessing suspected early prodromal stages of schizophrenia and beginning depressive disorder.


Hepatic resection provided long-term survival for patients with intermediate and advanced-stage resectable hepatocellular carcinoma.
Hepatic resection has the highest local controllability that results in long-term survival for hepatocellular carcinoma (HCC). This study aimed to investigate the role of hepatic resection in selected patients of intermediate and advanced stage. Clinical, pathological, and outcome data of 542 consecutive patients were retrospectively analyzed from a single center. The Kaplan-Meier method was used to estimate survival. Postoperative prognostic factors were evaluated using univariate and multivariate analyses. The 1-, 3-, and 5-year overall survival rates were 89.0, 64.3, and 53.0%, respectively. The 1-, 3-, and 5-year disease-free survival rates were 72.2, 44.5, and 34.2%, respectively. Preoperative α-fetoprotein level >400 ng/mL, macroscopic vascular invasion, microscopic portal vein thrombosis, multiple tumor nodules, and the largest tumor size >5 cm were significantly correlated with overall survival. When these clinical risk factors were used in a postoperative staging system, assigning one point for each factor, the total score was precisely predictive of long-term survival. For patients with surgery plus adjuvant TACE (transarterial chemoembolization), the median overall survival was 56 months (range 1-110 months) and the 5-year OS rate was 48.5%. Hepatic resection is efficient and safe for HCC patients of intermediate and advanced stage. The adjuvant TACE should be recommended for HCC patients with poor risk factors.


Feasibility of the new sutureless excimer laser-assisted non-occlusive anastomosis clip in a rabbit model.
The excimer laser-assisted non-occlusive anastomosis (ELANA) technique facilitates the construction of anastomoses without temporary occlusion of the recipient artery. Experiments aimed at simplifying the technique eventually resulted in a sutureless ELANA slide (SEsl) anastomosis. After the first clinical use, new insights lead to the application of a clip at the back of the device, the SELANA clip (SEcl). The SEcl offers a distinct advantage over the SEsl since no sealant is necessary. In this study, we determine the feasibility of the SEcl anastomosis in an in vivo rabbit model. 15 SEcl anastomoses and 15 conventional ELANA anastomoses were created on the abdominal aorta in 5 rabbits. Mean application times, flap retrieval rates, hemostasis, and burst pressures were assessed. The mean application time of the SEcl anastomoses was 11.4 min versus 39.0 min for the ELANA anastomoses (mean difference, 27.6 min; 95% CI, 20.6-34.7). The flap retrieval rate of the SEcl anastomoses (14/15) was not inferior to the flap retrieval rate of the ELANA anastomoses (13/15). Direct hemostasis was achieved in 13/15 (87%) SEcl anastomoses and in 14/15 (94%) ELANA anastomoses. All SEcl anastomoses were resistant to provoked pressures until 250 mmHg. The SEcl anastomosis is technically feasible in in vivo experiments. Mean application time, flap retrieval rate, hemostasis, and burst pressure are not inferior to the conventional ELANA anastomosis. Further long term experiments should be performed to assess safety, patency, and reendothelialization.


Strategies for 3D bioprinting of spheroids: A comprehensive review.
Biofabricated tissues have found numerous applications in tissue engineering and regenerative medicine in addition to the promotion of disease modeling and drug development and screening. Although three-dimensional (3D) printing strategies for designing and developing customized tissue constructs have made significant progress, the complexity of innate multicellular tissues hinders the accurate evaluation of physiological responses in vitro. Cellular aggregates, such as spheroids, are 3D structures where multiple types of cells are co-cultured and organized with endogenously secreted extracellular matrix and are designed to recapitulate the key features of native tissues more realistically. 3D Bioprinting has emerged as a crucial tool for positioning of these spheroids to assemble and organize them into physiologically- and histologically-relevant tissues, mimicking their native counterparts. This has triggered the convergence of spheroid fabrication and bioprinting, leading to the investigation of novel engineering methods for successful assembly of spheroids while simultaneously enhancing tissue repair. This review provides an overview of the current state-of-the-art in spheroid bioprinting methods and elucidates the involved technologies, intensively discusses the recent tissue fabrication applications, outlines the crucial properties that influence the bioprinting of these spheroids and bioprinted tissue characteristics, and finally details the current challenges and future perspectives of spheroid bioprinting efforts in the growing field of biofabrication.


Cholecystectomy.
We retrospectively reviewed 360 consecutive cholecystectomies done by the four surgeons in our private group practice. No patient had dehiscence of the wound or evisceration. One patient had a seroma, which was opened in the office, but the fluid contained no white blood cells or bacteria on smear, and the culture was negative. No deaths occurred during the hospitalization or within 30 days after the operation. Routine perioperative antibiotics were used, and most wounds were drained with closed suction drainage. Routine intraoperative cholangiography was also done. On the basis of the favorable morbidity and mortality in this large group of patients and a review of the literature, we recommend the routine use of antibiotics and cholecystectomy for most patients with gallstones.


Meta-analysis is not enough: The critical role of pathophysiology in determining optimal care in clinical nutrition.
Evidence based medicine has preferably been based on prospective randomized controlled trials (PRCT's) and subsequent meta-analyses in many fields including nutrition and metabolism. These meta-analyses often yield convincing, contradictory or no proof of effectiveness. Consequently recommendations and guidelines of varying validity and quality have been published, often failing to convince the medical, insurance and government worlds to support nutritional care. Causes for lack of adequate proof of effectiveness are manifold. Many studies and meta-analyses lacked pathophysiological depth in design and interpretation. Study populations were not homogenous and endpoints not always clearly defined. Patients were included not at nutritional risk, unlikely to benefit from nutritional intervention. Others received nutrients in excess of requirements or tolerance due to organ failure. To include all available studies in a meta-analysis, study quality and homogeneity were only assessed on the basis of formal study design and outcome rather than on patient characteristics. Consequently, some studies showed benefit but included patients suffering harm, other studies were negative but contained patients that benefited. Recommendations did not always emphasize these shortcomings, confusing the medical and nutritional community and creating the impression that nutritional support is not beneficial. Strong reliance on meta-analyses and guidelines shifts the focus of education from studying clinical and nutritional physiology to memorizing guidelines. To prevent or improve malnutrition more physiological knowledge should be acquired to personalize nutritional practices and to more correctly value and evaluate the evidence. This also applies to the design and interpretation of PRCT's and meta-analyses.


Zoogeography and parallel level-bottom communities of the meiobenthic harpacticoida (Crustacea, Copepoda) of Bermuda.
Twenty nine harpacticoid copepods are new to Bermuda and significant changes are noted in the distribution records of several species. Six temporary groups are organized to separate the copepods on their apparent zoogeographical ranges: (1) cosmopolitan, (2) warm temperate-tropical, (3) North Atlantic, (4) North Atlantic-Mediterranean, (5) Endemic to Bermuda and (6) uncertain. These six artificial groups do not necessarily correspond to the standard zoogeographical provinces. Endemism of the Bermudian harpacticoids is similar to the rates reported and predicted for other fauna on North Atlantic Islands. Low endemic rates probably reflect changing environmental conditions during the late Pleistocene.Three distinct harpacticoid isocommunities are reported. The associations are similar to harpacticoid assemblages found in similar sediment types in different parts of the world. All three associations are in agreement with Thorson's (1957) concept of the parallel level-bottom community.


Novel structural organisation of a Mus musculus DBA/2 chromosome shows a fixed position for the centromere.
Chromosome 1 of the inbred mouse strain DBA/2 shows an unusual polymorphism associated with its centromeric satellite DNA sequences. The minor satellite array has undergone amplification and is present as two blocks separated by major satellite sequences. Both minor satellite blocks appear to carry the sequence motif necessary for CENP-B protein binding. Despite this apparent similarity the functional centromere, as defined by the location of CREST antigens, appears to form only within the more terminal block. The two blocks also vary in that sister chromatid association only occurs with this more terminal block.


Interleukin 2 and its receptor: structure, function and therapeutic potential.
In this review, salient molecular, biochemical and functional features of human interleukin 2 (IL-2), its membrane receptor, and its clinical relevance are outlined. We also describe experimental systems, where observed biological or pharmacological effects of IL-2 could be applied to corresponding clinical situations. In particular, IL-2 has been intensively studied in the context of cancer therapy. We discuss the rationale for the use of IL-2 in cancer treatment and our experience in this area. A better understanding of the IL-2 system and, specifically, the nature of signals transduced through it will allow us to manipulate the immune response in a variety of different ways, resulting in new approaches to investigation of immune responsiveness in general. This may have a profound impact on clinical medicine.


Molecular detection of Leishmania infantum and Leishmania tropica in rodent species from endemic cutaneous leishmaniasis areas in Morocco.
Leishmaniasis remains a major public health problem in African nations, including Morocco, where little is known about the vertebrate reservoirs involved in the causal parasites' transmission cycles. The present study investigates the role of rodent species as potential reservoirs of Leishmania spp. in central Morocco, where both L. tropica and L. infantum have been reported. Rodents were caught from 22 sites in central Morocco, by using Sherman metal traps, and identified morphologically. For each specimen, genomic DNA was extracted from different tissues using the Speed Tools DNA extraction Kit. Then, samples were PCR-analyzed, targeting the SSU rRNA gene to detect Leishmania spp. DNA, followed by amplification of the internal transcribed spacer 1 (ITS1) and its sequencing to identify the species. A total of 197 rodents belonging to ten species were captured and identified: Rattus rattus (40.61%), Mus musculus (25.38%), Apodemus sylvaticus (8.63%), Mus spretus (7.11%), Meriones shawi (5.58%), Rattus norvegicus (4.57%), Meriones libycus (3.05%), Mastomys erythroleucus (2.03%), Gerbillus campestris (2.03%) and Lemniscomys barbarus (1.01%). Molecular analysis revealed the presence of Leishmania species in 18 specimens: six R. rattus (out of 80 captured; 7.5%), 11 M. musculus (out of 50 captured; 22%), and one R. norvegicus (out of 9 captured; 11.11%). To the best of our knowledge, L. infantum and L. tropica were identified in rodent species for the first time in Morocco. These findings suggest that rodent species may be involved in L. infantum and L. tropica transmission cycles in this country but that further studies are needed to confirm their role as reservoirs of Leishmania species in Morocco.


Testicular Epidermoid Cyst: A Rare Case Report.
Testicular epidermoid cysts (TECs) are rare benign testicular neoplasms. Recently, testicular epidermoid cysts (TECs) are listed as teratoma of prepubertal type, however it is still difficult to differentiate the epidermoid cyst from malign testicular tumor. Therefore, we would like to report testicular epidermoid cyst at our institution. A 67-year-old man from Indonesia, presented with chronical painless mass of testis since one year ago. On physical examination obtained normal penile structure with descended testicles, palpable intrascrotal mass with size of 10 × 7 × 5 cm, firm consistency, immobile, without any tenderness, and no lymphadenophaty in groin. Scrotal USG showed intratesticular mass, homogenous parenchym, showed no vascularization during Doppler examination. Histopathological examination revealed the specimen of right scrotum with size of 12.5 cm × 8.5 cm × 6.1 cm with red-brownish colored, during lamellation, obtained encapsulated mass with size of 12.2 cm × 7.9 cm × 6 cm, hollowed space filled with porridge-like texture with capsule thickness of 0.1-0.3 cm. Epidermoid cysts are benign lesions occurring on the skin usually, however, it rarely occurs in intratesticular area. Most of the cases (60%) presented with the typical onion-ring phenomenon. Histopathological findings commonly revealed typical well-defined cyst lined by a fibrous membrane. No skin appendages are found in the cyst's lumen and no germ cell neoplasm (GCN) is present in the adjacent testicular parenchyma. All testicular masses are considered malignant until proven otherwise. It is necessary to do accurate diagnosis for the prevention of unnecessary radical orchiectomy.


A graphic display system for use with a computerized tomographic scanner.
A system for the display and analysis of computerized axial tomography scans has been developed. Selected regions of scans can be outlined using a joystick, allowing rapid statistical analysis. The difference between two scans can be displayed, and coronal and sagittal sections as well as projected displays, can be produced from a series of transverse sections. A special purpose software system has been developed to allow programming on a logical level. The system is used both for the analysis of current scans and the retrospective accumulation of data from past scans.


Functional Characterization and Cyclization Mechanism of a Diterpene Synthase Catalyzing the Skeleton Formation of Cephalotane-Type Diterpenoids.
CsCTS, a new diterpene synthase from Cephalotaxus sinensis responsible for forming cephalotene, the core skeleton of cephalotane-type diterpenoids with a highly rigid 6/6/5/7 tetracyclic ring system, was functionally characterized. The stepwise cyclization mechanism is proposed mainly based on structural investigation of its derailment products, and further demonstrated through isotopic labeling experiments and density functional theory calculations. Homology modeling and molecular dynamics simulation combined with site-directed mutagenesis revealed the critical amino acid residues for the unique carbocation-driven cascade cyclization mechanism of CsCTS. Altogether, this study reports the discovery of the diterpene synthase that catalyzes the first committed step of cephalotane-type diterpenoid biosynthesis and delineates its cyclization mechanism, laying the foundation to decipher and artificially construct the complete biosynthetic pathway of this type diterpenoids.


Ankle injuries caused by seat belts.
Two cases of tri-malleolar frautures of the ankle caused by feet becoming entangled in loose seat belts are reported. Open reduction and internal fixation of all three malleolar fragments was carried out in each case with a satisfactory end result.


The Impact of Social Determinants of Health on Eye Care Utilization in a National Sample of People with Diabetes.
To evaluate the association of social determinants of health (SDoH) with eye care utilization among people with diabetes mellitus using the 2013-2017 National Health Interview Survey (NHIS). Retrospective cross-sectional study. Participants ≥ 18 years of age with self-reported diabetes. The SDoH in the following domains were used: (1) economic stability; (2) neighborhood, physical environment, and social cohesion; (3) community and social context; (4) food environment; (5) education; and (6) health care system. An aggregate SDoH score was calculated and divided into quartiles, with Q4 representing those with the highest adverse SDoH burden. Survey-weighted multivariable logistic regression models evaluated the association of SDoH quartile with eye care utilization in the preceding 12 months. A linear trend test was conducted. Domain-specific mean SDoH scores were calculated, and the performance of domain-specific models was compared using area under the curve (AUC). Eye care utilization in the preceding 12 months. Of 20 807 adults with diabetes, 43% had not used eye care. Greater adverse SDoH burden was associated with decrements in odds of eye care utilization (P < 0.001 for trend). Participants in the highest quartile of adverse SDoH burden (Q4) had a 58% lower odds (odds ratio [OR], 0.42; 95% confidence interval [CI], 0.37-0.47) of eye care utilization than those in Q1. The domain-specific model using economic stability had the highest performing AUC (0.63; 95% CI, 0.62-0.64). Among a national sample of people with diabetes, adverse SDoH were associated with decreased eye care utilization. Evaluating and intervening upon the effects of adverse SDoH may be a means by which to improve eye care utilization and prevent vision loss. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.


[Understanding and assessing the antidepressant drug-associated risk of bleeding].
Antidepressants, in particular selective serotonin reuptake inhibitors (SSRIs), are the most commonly prescribed psychopharmacological drug group. Thus, a precise knowledge of the expected adverse drug reactions is indispensable. The increased risk of bleeding events is well documented, especially in patients treated with SSRIs. However, many other antidepressant drug groups have also been implicated in increasing the risk of bleeding. In the following review, the thrombocytic serotonin system and the respective targets of the different antidepressants are explained. Subsequently, the available literature on bleeding under the respective antidepressant classes or individual substances is presented, using data from meta-analyses whenever possible. In addition to the risk of bleeding in general, individual bleeding entities are also considered, such as gastrointestinal and cerebral hemorrhages. Finally, the effects of other drugs that increase the risk of bleeding (i. e., nonsteroidal anti-inflammatory drugs, platelet aggregation inhibitors and anticoagulants) in combination with antidepressant drugs are discussed. The information presented here is meant to guide practitioner's decision making regarding an appropriate antidepressant pharmacotherapy based on the patient's individual risk constellation.


Endothelial cell protection and complement inhibition in xenotransplantation: a novel in vitro model using whole blood.
Studying the interactions between xenoreactive antibodies, complement and coagulation factors with the endothelium in hyperacute and acute vascular rejection usually necessitates the use of in vivo models. Conventional in vitro or ex vivo systems require either serum, plasma or anti-coagulated whole blood, making analysis of coagulation-mediated effects difficult. Here a novel in vitro microcarrier-based system for the study of endothelial cell (EC) activation and damage, using non-anticoagulated whole blood is described. Once established, the model was used to study the effect of the characterized complement- and coagulation inhibitor dextran sulfate (DXS, MW 5000) for its EC protective properties in a xenotransplantation setting. Porcine aortic endothelial cells (PAEC), grown to confluence on microcarrier beads, were incubated with non-anticoagulated whole human blood until coagulation occurred or for a maximum of 90 min. PAEC-beads were either pre- or co-incubated with DXS. Phosphate buffered saline (PBS) experiments served as controls. Fluid phase and surface activation markers for complement and coagulation were analyzed as well as binding of DXS to PAEC-beads. Co- as well as pre-incubation of DXS, followed by washing of the beads, significantly prolonged time to coagulation from 39 +/- 12 min (PBS control) to 74 +/- 23 and 77 +/- 20 min, respectively (P < 0.005 vs. PBS). DXS treatment attenuated surface deposition of C1q, C4b/c, C3b/c and C5b-9 without affecting IgG or IgM deposition. Endothelial integrity, expressed by positivity for von Willebrand Factor, was maintained longer with DXS treatment. Compared with PBS controls, both pre- and co-incubation with DXS significantly prolonged activated partial thromboplastin time (>300 s, P < 0.05) and reduced production of thrombin-antithrombin complexes and fibrinopeptide A. Whilst DXS co-incubation completely blocked classical pathway complement activity (CH50 test) DXS pre-incubation or PBS control experiments showed no inhibition. DXS bound to PAEC-beads as visualized using fluorescein-labeled DXS. This novel in vitro microcarrier model can be used to study EC damage and the complex interactions with whole blood as well as screen ''endothelial protective'' substances in a xenotransplantation setting. DXS provides EC protection in this in vitro setting, attenuating damage of ECs as seen in hyperacute xenograft rejection.


Predication of post-operative outcome of colectomy in ulcerative colitis patients using Model of End-Stage Liver Disease Score.
Model of End-Stage Liver Disease (MELD) score was developed to predict mortality in patients with liver disease. The aim of this study was to investigate the relationship between preoperative MELD score and 30-day surgical outcomes using the American College of Surgeons National Surgical Quality Improvement Program. Patients with ulcerative colitis (UC) (ICD: 556.X) who underwent colectomy were identified from NSQIP 2005 to 2013. The primary outcomes were bleeding complications, and overall morbidity and mortality. A total of 7534 UC patients undergoing colectomy were identified. Patients with a higher MELD score had a longer hospital stay; more bleeding; and cardiac, respiratory, renal, thromboembolic, and septic complications as well as mortality. Patients were stratified into 4 groups by MELD score: < 7, 7-11, 12-15, and > 15 and a stratified multivariate analysis was done. Patients with a MELD score 12-15 (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.1-1.3) and MELD > 15 (OR 2.6, 95%CI 1.5-4.7) were at significant risk for bleeding complication. Apart from the MELD score, the presence of ascites (OR 2.5, 95%CI 1.2-5.1) or varices (OR 1.0, 95%CI 1.01-1.03) was also significantly associated with post-operative bleeding complication. MELD 12-15 and MELD > 15 were also found to be risk factors for overall morbidity (OR 5.3, 95%CI 1.8-15.7; OR 10.3, 95%CI 3.6-29.7, respectively) and mortality (OR 3.3, 95%CI 1.3-8.4; OR 5.9, 95%CI 2.4-14.6, respectively). UC patients with a higher MELD score were associated with a higher post-colectomy morbidity and mortality. MELD score > 11 was an independent indicator for post-operative bleeding, and overall complications and mortality.


[Cardiomyopathy induced by frequent premature ventricular contractions].
We report on the rare case of 7-year-old child presenting with frequent and apparently benign premature ventricular complexes (VPC) and left ventricular dysfunction. No structural disease of the heart was seen at cardiological evaluation. Eighteen months after the introduction of an antiarrhythmic treatment with low-dose bisoprolol, Holter monitoring showed 70,000 VPC in 24h with left ventricular function remaining decreased. Six months after increasing the dose of bisoprolol, the VPC were less frequent and left ventricular function was completely normalized. This case was characteristic of a cardiomyopathy induced by frequent premature ventricular contractions.


Validation of a Greek version of the oral health impact profile (OHIP-14) for use among adults.
To test the validity of the short form of the Oral Health Impact Profile (OHIP-14) for use among adults in Greece. The original English version of the OHIP-14 was translated using the forward-backward technique, pilot-tested, and then applied to 211 adults aged 35 years and above. The questionnaire was filled out during face-to-face interviews conducted by one dentist, while individuals were asked to undergo a clinical examination. The internal consistency of the questionnaire was evaluated using Cronbach's alpha (α) coefficient and inter-item and item-total correlations. Discriminant and convergent validities were assessed. Cronbach's α was estimated to be 0.90. Inter-item correlations coefficients ranged from 0.10 to 0.83, while item-total correlations coefficients from 0.44 to 0.76. Significant associations were found between OHIP-14 and the decayed, missing and filled teeth (DMFT) and oral hygiene, supporting the ability of the questionnaire to discriminate between individuals with and without impacts. The OHIP-14 total score was highly associated with self-perceived oral health status (r(s) = 0.57; p = 0.01), as well as with self-assessment of oral satisfaction (r(s) = 0.55;p = 0.01). Similar results were observed by investigating the relationship between the latter questions and each domain score as well as in various sub-groups analyses. The OHIP-14 is a reliable and valid questionnaire for the assessment of OHRQoL among adults in Greece.


The Interrelationship Between FYN and miR-128/193a-5p/494 in Imatinib Resistance in Prostate Cancer.
C-KIT is a receptor tyrosine kinase with oncogenic properties overexpressed in PCa cases. Through the use of an alternative promoter, a truncated c-KIT protein (tr-KIT) of 30-50 kDa is generated, lacking the extracellular and transmembrane domain. Tr-KIT promotes the formation of a multi-molecular complex composed of Fyn, Plcγ1, and Sam68. Imatinib blocks the activity of full-length c-KIT but has no effect on tr-KIT. LNCaP is the human PCa cell line that shows tr-KIT overexpression and PC3 does not show tr-KIT overexpression. miR-128/193a- 5p/494 are miRNAs targeting FYN, PLCγ1, and SAM68 combinatorially. The study's question is: can miR-128/193a- 5p/494 be related to imatinib resistance in PCa? LNCaP and PC3 cells were treated with imatinib in IC50 doses. Before and after imatinib administration, RNA was isolated and cDNA conversion was performed. By qPCR analysis, expression changes of tr-KIT specific pathway elements and miR-128/193a-5p/494 were analyzed before and after imatinib administration. After imatinib administration, miR-128/193a-5p/494 were significantly overexpressed in LNCaP cells while downregulated significantly in PC3 cells (p<0.05). Also, FYN was upregulated in LNCaP cells (p<0.05) but there was no change in PC3 after imatinib administration. Especially upregulation of FYN may sponge miR128/193a-5p/494 and downregulate their transcriptional activity in LNCaP cells having tr-KIT activity. So, miR-128/193a-5p/494 may have a critical role in imatinib resistance via a tr-KIT pathway.


Choice of Formula and Accuracy of Fetal Weight Estimation in Small-for-Gestational-Age Fetuses.
The purpose of this study was to identify the most accurate sonographic models for fetal weight estimation in specific subgroups of small-for-gestational-age (SGA) fetuses. We conducted a retrospective study of women who delivered an SGA neonate and underwent a sonographic estimation of fetal weight within 7 days of delivery in a single tertiary center (n = 370). The accuracy of fetal weight estimation was compared for 33 sonographic models (27 nontargeted and 6 targeted SGA- or low-birth-weight-specific models) in specific subgroups of SGA fetuses: early versus late SGA, asymmetric versus symmetric, and presence of Doppler abnormalities. A wide variation in the accuracy of the different models was found (systematic error, -12.5% to 15.1%; random error, 7.8% to 15.5%). Most nontargeted models tended to systematically overestimate the weight of SGA fetuses. The best performing model in the overall SGA group was the targeted model of Scott et al (J Ultrasound Med 1996; 15:669-672; systematic error ± random error, -2.8% ± 8.3%). However, the optimal models varied for different subgroups of SGA fetuses, and in most cases the targeted models were the most accurate. An approach that used the optimal model for each subgroup of SGA fetuses compared with the uniform use of the model of Scott et al for all SGA fetuses was associated with a lower systematic error (-0.38% versus -2.8%; P < .001) and a higher proportion of weight estimations within 5%, 10%, and 15% of birth weight (48.4% versus 40.8%; P= .038; 78.6% versus 71.4%; P= .022; 95.1% versus 89.2%; P = .003, respectively). Sonographic models in current use for fetal weight estimation in SGA fetuses have significant errors, and their performance varies for specific subgroups of SGA fetuses. An approach that uses subgroup-specific models may improve the accuracy of weight estimation among SGA fetuses.


The clinical effect and the effect on serum IgG antibodies to peripheral nerve tissue of plasma exchange in patients wit Guillain-Barré syndrome.
The mixed haemagglutination technique was used to demonstrate IgG antibodies to peripheral nerve tissue in sera from patients with the Guillain-Barré syndrome. The clinical effect and the effect on the antibodies of plasma exchange were examined in 18 patients. Neurological examination with muscle testing and neurophysiological examination of the patients were performed before and immediately after plasma exchange. Before the exchange antibodies were detected in sera from 11 of the patients. These patients showed clinical improvement during the treatment. After plasma exchange, antibodies were detected in sera from only two of the patients. The seven patients without detectable antibodies showed no clinical improvement.


Comparisons of yeast florae from natural substrates and larval guts of southwestern Drosophila.
The yeast florae in the natural substrates of four desert and three non-desert Drosophila species were compared both qualitatively and quantatively to the yeast present in the guts of Drosophila larvae living in those substrates. The desert species breed in rotting cacti and the other Drosophila were found breeding in necrotic oranges. Larvae of one cactophilic species, D. mojavensis, and larvae of all of the species utilizing oranges (D. melanogaster, D. pseudoobscura, and D. arizonensis) were found to contain non-random samples of the yeasts available in their respective substrates. Larval preference behavior is most likely responsible for these differences. The other cactophilic Drosophila (D. nigrospiracula, D. mettleri, and D. pachea) did not exhibit significant differences when the yeast florae of their larvae and substrates were compared. Selective feeding by larvae appears to be related to the degree of polyphagy in that only larvae of polyphagous species are selective. Trade-off between generalism and specialism at two biological levels is discussed.


Ionic liquid combined with carbon nanotubes: a soft material for the preconcentration of PAHs.
The combination of ionic liquids with carbon nanotubes has opened a new possibility of ionic liquids as modifiers for carbon nanotubes. Upon being ground into ionic liquids, carbon nanotube bundles are untangled, and the resultant fine bundles form a network structure. This is due to the possible specific interaction between the imidazolium ion component and the p-electronic nanotube surface. The resultant soft material has a high capacity to adsorb/absorb analytes from samples. In this work, the soft material was prepared by mixing 15 mg of carbon nanotubes with 300 μL of IL. The soft material was immobilized on cotton fibers to perform the preconcentration of aromatic compounds such as PAHs from river water samples. The most important fact is the synergic effect between the ionic liquid and the carbon nanotubes which results in a high capacity to preconcentrate analytes. In fact, the sorption capacity of 15 mg of the soft material containing 0.55 mg of MWNT and 11 μl of IL is two times higher than the capacity of 15 mg of MWNT and 3.7 times higher than that of 100 μl IL.


Inappropriate emergency department visits.
Guidelines adopted in 1982 by the American College of Emergency Physicians were used to determine appropriate and inappropriate emergency department (ED) utilization patterns at three community hospitals during a two-week period in August 1983. In all, 3,130 visits were examined. There was an overall inappropriate visit rate of 10.8%, although considerable variation was observed among the three hospitals. Subgroups with the highest inappropriate visit rates included the following: 1) persons with Medicaid as the primary payment source (17.3%); 2) children aged 5 years or younger (15.2%); 3) those unable to identify a personal physician (14.1%); 4) unemployed persons (13.1%); 5) patients making visits during regular office hours (12.6%); and 6) those failing to attempt to contact their personal physicians (12.4%). These variations in inappropriate usage were all statistically significant at the P less than .05 level or better. Inability to identify a personal physician emerged as the most pervasive influence on inappropriate ED visit rates (P less than .001).


The effectiveness of patient-centered care vs. usual care in type 2 diabetes self-management: A systematic review and meta-analysis.
Patient-centered care in diabetes self-management might be a significant factor in improving health outcomes of adults with type 2 diabetes, yet the supporting evidence is inadequate. This review aimed at assessing the effectiveness of patient-centered self-management care interventions on glycemic control (HbA1c) and self-care behaviors compared with usual care. CINAHL, PubMed, Cochrane Library, Google Scholar, and the HEC Digital Library were searched for studies in English language that assessed patient-centered self-management educational and/or behavioral interventions in adults aged 18 years or older with type 2 diabetes from 2005 to 2020. Interventional studies with at least 3 months of follow-up and reporting on self-care outcomes such as glycemic control (HbA1c) and self-care behaviors including diet control, physical activity, foot care, and medication adherence were included. Of 168 identified records, 24 were found eligible comprising 20 RCTs and four QESs with total 4,083 participants. The meta-analysis involved 19 RCTs that provided enough information for a pooled estimate of HbA1c. Compared with the control group, patient-centered self-management interventions significantly lowered HbA1c, -0.56 (95% CI -0.79, -0.32). Stratified analysis for HbA1c with respect to various aspects of intervention showed larger effects in interventions employing both educational and behavioral components, -0.66 (95% CI -0.97, -0.34); spanned over shorter (<03 months) duration, -0.85 (95% CI -1.28, -0.43); administered by nurses, -0.80 (95% CI -1.44, -0.16); and delivered in community settings -0.70 (95% CI -1.14, -0.26). This systematic review provided evidence supporting the effectiveness of patient-centered self-management care interventions in improving glycemic control and self-care behaviors in adults with type 2 diabetes and identified key features of intervention contributing toward success.


Glutaric aciduria type I with high residual glutaryl-CoA dehydrogenase activity.
Two brothers with dystonia and slight MRI changes in the basal ganglia had normal urinary glutaric acid excretion, but slightly increased 3-hydroxyglutarate and conjugated glutarate excretions. Both siblings have high residual glutaryl-CoA dehydrogenase activity, and are compound heterozygotes for two mutations - R227P and V400M reported to be disease-causing in patients with glutaric aciduria type I.


Optimization of microencapsulation conditions of transglutaminase by freeze drying.
Transglutaminase (TG), which is an important enzyme for food processing, can enhance the firmness, viscosity and water binding capacity of food products by catalyzing the cross-linking reaction of proteins. Since preservation of the enzyme activity is essential, the production of microencapsulated powder form of TG can be a great challenge to maintain its initial activity. In this study, TG was microencapsulated using a freeze drying technique and the effects of homogenization conditions and coating material ratios on the enzyme activity were investigated using D-optimal combined design. Mannitol, gum arabic and casein were chosen as coating materials and different homogenization times (1-5 min) and homogenization rates (11,200-20,000 rpm) were applied. The optimum conditions which ensure the maximum enzyme activity have been determined as 11,200 rpm of homogenization rate, 1.27 min of homogenization time, and in addition a mixture of mannitol, gum arabic and casein with ratios 38.2, 40.2, and 21.6%, respectively. Most of the activity loss occurred in the homogenization stage and the coating materials preserved enzyme activity during freeze drying. At the optimum point, the remaining activity of the microencapsulated TG was 93% while that of the crude (without coating materials) TG was 64% at the same drying conditions. Moreover, the effects of the microencapsulation conditions on the physical properties of powder such as moisture content, color, particle, bulk and tapped densities, porosity and flowability were determined.


Steroid synthesis in rat brain cell cultures.
Primary cultures derived from neonatal rat forebrains were established and cultured for several weeks. They grow entirely as glial cultures composed of oligodendrocytes and astrocytes. Glial cells undergo maturation and differentiation in culture. This was shown by measuring the oligodendroglial enzyme 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase), a specific marker for expression of oligodendrocyte differentiation. CNPase activity increased from days 10-21 of culture. Both cell types were characterized by indirect immunofluorescence staining using monoclonal antibodies to galactocerebroside (Gal C) and myelin basic protein (MBP) for oligodendrocytes, and glial fibrillary acidic protein (GFAP) for astrocytes. Using the above criteria, we measured about 60% oligodendrocytes and 40% astrocytes after 3 weeks of culture. Oligodendrocytes, expressing Gal C and MBP, were highly immunoreactive to monospecific polyclonal antibodies to the cytochrome P-450scc, enzyme involved in the synthesis of pregnenolone from cholesterol. After incubation of glial cultures with [3H]mevalonolactone in the presence of mevinoline and trilostane, biosynthesis of [3H]cholesterol, [3H]pregnenolone (P) and [3H]pregn-5-ene-3 beta, 20 alpha-diol (20-OHP) was demonstrated. Steroid biosynthesis was related to oligodendroglial differentiation, as the initial and rapid rate of increase in CNPase activity was found to occur at the same time as the onset of steroid synthesis. Both reached a maximum at 3 weeks of culture and remained stable for several weeks. Steroid synthesis was increased by dibutyryl cAMP (0.2 mM), as well as by dexamethasone (10 nM). When aminoglutethimide, a potent inhibitor of cytochrome P-450scc, was added during the incubation of cells with [3H]mevalonolactone, [3H]cholesterol accumulated in the cells. After the release of aminoglutethimide blockade, [3H]20-OHP was the major steroid produced and released in the culture medium. The demonstration of de novo steroid biosynthesis and of the cholesterol side-chain cleavage cytochrome P-450 in normal rat glial cells brings additional support to the concept of "neurosteroids".


Assessment of intra- and inter-regional interrelations between GABA+, Glx and BOLD during pain perception in the human brain - A combined 1H fMRS and fMRI study.
To explore brain activity and the related neurochemical processes, current research focuses increasingly on the combined acquisition of 1H MR spectra and fMRI data to investigate potential associations between local metabolite resting state levels and stimulus-induced BOLD signal changes. In this study, whole-brain fMRI measurements and localized functional 1H MEGA-PRESS MRS scans were conducted at 3T in healthy subjects prior to and during acute pain stimulation to quantify resting state GABA+/tCr and Glx/tCr levels in the insular cortex together with their stimulus-induced changes and to explore associations between these neurochemical parameters with intra-regional but also inter-regional BOLD responses. Inter-regionally, a significant negative correlation between the BOLD signal of a cluster in the supplementary motor area with overlap to the mid-cingulate cortex (R = -0.56, p = 0.004) and the insular resting state GABA+/tCr was obtained. Furthermore, pain induced insular ΔGlx was significantly positively associated with the BOLD signal in the left superior frontal gyrus, left and right inferior frontal gyrus, left inferior parietal lobe, left superior temporal gyrus, left anterior insula and right posterior insula, with R values ranging from 0.59 to 0.73 (p < 0.005). No intra-regional association was observed between BOLD and metabolite measures. These findings point toward interactions between metabolite levels and stimulus-induced BOLD responses in brain regions belonging to the pain processing network. The combination of fMRS and fMRI provides a powerful tool to improve our understanding about the complex system of neurochemical processes and brain activity within brain networks.


Pharmacokinetics and tolerability of intravenous infusion of adenosine (SUNY4001) in healthy volunteers.
To examine the tolerability and disposition of i.v. adenosine (SUNY4001) in healthy male Japanese volunteers. SUNY4001 was infused i.v. for 6 min at 0 (placebo), 60, 100, 120 and 140 microg kg-1 min-1 in a dose-escalating manner in 30 healthy subjects. Adenosine and its metabolites were determined in the plasma and urine. Only plasma hypoxanthine was increased from 3 min during until 5-10 min after SUNY4001 infusion at the higher rates without any significant dose-related changes in plasma adenosine, inosine, xanthine or uric acid, or in urinary adenosine and all metabolites compared with the placebo. There was a dose-related increase in the incidence of subjective symptoms such as heat sensation, flushed face, dyspnoea, chest discomfort, etc. Transient and self-subsiding episodes of second-degree atrioventricular block were found in two subjects each at the higher doses. Adenosine infusion at < or = 140 microg kg-1 min-1 was concluded to be generally well tolerated.


The effect of patellar taping on joint reaction forces during squatting in subjects with Patellofemoral Pain Syndrome (PFPS).
The mechanisms of pain reduction have not completely been established following patellar taping in subjects with patellofemoral pain syndrome (PFPS); although it might be related to alteration in the kinetics of the patellofemoral joint. Patellofemoral Joint Reaction Force (PFJRF) of eighteen subjects with PFPS and eighteen healthy subjects as controls were assessed by a motion-analysis system and one force plate. This procedure was performed on the affected knee of subjects with PFPS, before, during and finally after patellar taping during unilateral squatting. A similar procedure was also performed on the unaffected knees of both groups. The mean values of PFJRF prior to taping (2025N, SD 347N) were decreased significantly following a period of taping (1720N, SD 303N) (P<0.05). There were no significant differences between the mean values of PFJRF among controls (1922N, SD 398N) and subjects with PFPS prior to taping (P>0.05) which might be due to small sample size in both groups and large variability observed in the study. Decreased values of PFJRF may explain the mechanism of pain reduction following patellar taping in subjects with PFPS.


Effect of cellulose nanofiber content on flexural properties of a model, thermoplastic, injection-molded, polymethyl methacrylate denture base material.
Cellulose nanofiber (CNF) made from wood-derived fiber is considered as a potential alternative reinforcing material to conventional fibers. The aim of this study was to investigate the effect of CNF on the flexural properties of CNF-reinforced, injection molded, polymethyl methacrylate (PMMA) denture base material. Test specimens were fabricated from a model thermoplastic denture base resin using the injection molding technique. The resin pellets were mixed with CNF (to obtain different weight percentages 5, 10, 15, and 23 wt%). PMMA without CNF served as the control (0 wt%). Prior to the testing, the test specimens (n = 12/group) were water-immersed at 37 °C water for 50 h. The flexural strengths and moduli of the specimens were determined using three-point bending tests. Statistical evaluation included a one-way analysis of variance and the Student-Newman-Keuls test (α = 0.05). The mean and standard deviation of flexural strengths with the addition of 0, 5, 10, 15 and 23% CNF were 49.4 (±0.7), 56.4 (±1.3), 63.5 (±2.0), 72.0 (±4.7), and 96.8 (±4.0) MPa, respectively. The mean and standard deviation of flexural modulus with the addition of the same concentrations of CNF were 1.31 (±0.02), 1.56 (±0.05), 1.99 (±0.14), 2.40 (±0.15), and 3.96 (±0.08) GPa, respectively. The flexural strengths and moduli of the CNF-reinforced PMMA were significantly higher than those of pure PMMA (p < 0.05). Hence, incorporation of CNF can significantly improve flexural properties of a thermoplastic PMMA denture base material.


Providing optimal oral health.
Oral health is achieved with adequate nutrition, a properly functioning masticatory apparatus, a flow of saliva, and mechanical cleaning of the oral cavity by artificial means. Interruption of one or more of these factors produces significant changes in the oral cavity, leading to collection of debris and formation of plaque, tartar, dental caries, and periodontal disease. The astute nurse will consider these factors in her overall assessment of the client and will institute in the total plan of care specific nursing measures to prevent, minimize, or reverse changes in the oral cavity. The choice of agents to be used for oral hygiene should be based on a knowledge of their characteristics and function rather than on their convenience of preparation or tradition. The method of implementation should be determined by the client's status mentally and physically, and the frequency of care should be determined by a continued evaluation of the results achieved. Too often in nursing we accept into use agents or methods introduced for care with little or no evidence of their effectiveness, and tend to perpetuate their use because of their convenience or our assumptions that they are beneficial. A review of the literature regarding oral hygiene has helped focus on the areas of agreement as well as on the areas of question regarding the efficacy of the components of oral care: the criteria for assessment, the agents selected, the methods used, and the frequency required. Further scientific inquiry should be done by nurses to build on the knowledge and criteria enumerated--specifically, to define further criteria for assessing changes in the condition of the oral cavity--and to study the effects of various agents on the pH of the mouth.


Relationship of exercise volume to improvements of quality of life with supervised exercise training in patients with type 2 diabetes in a randomised controlled trial: the Italian Diabetes and Exercise Study (IDES).
A positive impact of exercise intervention programmes on quality of life (QoL) may be important for long-term patient compliance to exercise recommendations. We have previously shown that QoL improves significantly with supervised exercise, whereas it worsens with counselling alone, in patients with type 2 diabetes from the Italian Diabetes and Exercise Study (IDES). Here, we report data on the relationship between changes in QoL and volume of physical activity/exercise in these individuals. This multicentre parallel randomised controlled, open-label, trial enrolled sedentary patients with type 2 diabetes (n = 606 of 691 eligible) in 22 outpatient diabetes clinics. Patients were randomised by centre, age and diabetes treatment using a permuted-block design to twice-a-week supervised aerobic and resistance training plus exercise counselling (exercise group) versus counselling alone (control group) for 12 months. Health-related QoL was assessed by the 36-Item Short Form (SF-36) Health Survey. In the exercise group (n = 268 of 303 randomised), there was a trend for increasing QoL with increasing exercise volume, with significant improvement of the physical component summary (PCS) measure only above 17.5 metabolic equivalents h⁻¹ week⁻¹ and a clear volume-relationship for the mental component summary (MCS) measure. A relationship with volume of physical activity also was observed in the control group (n = 260 of 303 randomised), despite overall deterioration of all scores. Independent correlates of improvements in both PCS and MCS were exercise volume, study arm and, inversely, baseline score. This large trial shows a relationship between changes in physical and mental health-related QoL measures and volume of physical activity/exercise, with supervised exercise training also providing volume-independent benefits.


Medical decision making among patients with heart failure - does migration background matter?
Some studies, mainly coming from the U.S., indicate disparities in heart failure (HF) treatment according to migration/ethnicity. However, respective results are inconsistent and cannot be transferred to other health care systems. Thus, we will address the following research question: Are there differences in the diagnosis and management of HF between patients with and without a Turkish migration background in Germany? A factorial experimental design with video vignettes was applied. In the filmed simulated initial encounters, professional actors played patients, who consulted a primary care physician because of typical HF symptoms. While the dialog was identical in all videos, patients differed in terms of Turkish migration history (no/yes), sex (male/female), and age (55 years/75 years). After viewing the video, primary care physicians (N = 128) were asked standardized and open ended questions concerning their decisions on diagnosis and therapy. Analyses revealed no statistically significant differences (p < 0.05), but a consistent tendency: Primary care doctors more often asked lifestyle and psychosocial questions, they more often diagnosed HF, they gave more advice to rest and how to behave in case of deterioration, they more often auscultated the lung, and more often referred to a specialist when the patient has a Turkish migration history compared to a non-migrant patient. Differences in the medical decisions between the two groups ranged between 1.6 and 15.8%. In 10 out of 12 comparisons, differences were below 10%. Our results indicate that are no significant inequalities in diagnosis and management of HF according to a Turkish migration background in Germany. Primary care physicians' behaviour and medical decision making do not seem to be influenced by the migration background of the patients. Future studies are needed to verify this result and to address inequalities in HF therapy in an advanced disease stage.


A morphological study on gills of the brown shrimp, Penaeus aztecus.
The gills of Penaeus aztecus were examined by light and electron microscopy. They are dendrobranchiate, consisting of a central axis with biserially arranged branches that subdivide into bifurcating filaments. A septum divides the lumina of these structures into afferent and efferent channels. Hemolymph from the sternal sinus flows through the afferent channels into the filaments where it is directed into the efferent channels and finally to the pericardial cavity. In addition to these channels, numerous blood vessels permeate the gill. The cuticle covering the gill overlies a thin epithelium which is separated from hemolymph by a basal lamina. The epithelium, which is active in cuticle secretion, has a series of pillar processes that form subcuticular lacunae. The apical membranes of epithelial cells become folded in shrimp exposed to hypo- and hyperosmotic salinities. Granular cells that contain elaborate Golgi apparati and several types of granules are present throughout the gill. Nephrocytes resembling glomerular podocytes line the efferent channels. A large nerve traverses the septum in the axis.


Real-world experience of patients with multiple myeloma receiving ide-cel after a prior BCMA-targeted therapy.
Most patients with multiple myeloma experience disease relapse after treatment with a B-cell maturation antigen-targeted therapy (BCMA-TT), and data describing outcomes for patients treated with sequential BCMA-TT are limited. We analyzed clinical outcomes for patients infused with standard-of-care idecabtagene vicleucel, an anti-BCMA chimeric antigen receptor (CAR) T-cell therapy, at 11 US medical centers. A total of 50 patients with prior BCMA-TT exposure (38 antibody-drug conjugate, 7 bispecific, 5 CAR T) and 153 patients with no prior BCMA-TT were infused with ide-cel, with a median follow-up duration of 4.5 and 6.0 months, respectively. Safety outcomes between cohorts were comparable. The prior BCMA-TT cohort had a lower overall response rate (74% versus 88%; p = 0.021), median duration of response (7.4 versus 9.6 months; p = 0.03), and median progression-free survival (3.2 months versus 9.0 months; p = 0.0002) compared to the cohort without prior BCMA-TT. All five patients who received a prior anti-BCMA CAR T responded to ide-cel, and survival outcomes were best for this subgroup. In conclusion, treatment with ide-cel yielded meaningful clinical responses in real-world patients exposed to a prior BCMA-TT, though response rates and durability were suboptimal compared to those not treated with a prior BCMA-TT.


Dried blood spots: An evaluation of utility in the field.
Use of dried blood spots (DBS) offers advantages over serum samples in studies conducted in resource-poor settings. The aim of this study was to compare the number of adequate spots collected across different demographic groups. Five DBS were collected from 3316 individuals aged 0-49 years in Tianjin, China for a measles antibody study; DBS were rated "adequate" or "inadequate." Linear regression, with the number of adequate DBS on a card as the outcome variable, was used to test for predictors of DBS adequacy. There were 0 adequate DBS for 23% of participants and 5 adequate DBS for 24%. Mean number of adequate DBS was 1.68 in infants (<12 months), 2.57 (1-9 years), 3.49 (10-29 years), 3.08 (30-49 years). The number of adequate DBS increased over the study; the mean number of adequate DBS for the five years 2011-2015 were 1.21, 2.52, 3.40, 2.22, and 3.62, respectively. DBS quality was not related to measles IgG antibodies. DBS are an alternative for adults and children but pose challenges in infants, and improve with experience. In a resource-limited environment or in a scenario where more invasive techniques like venipuncture may be less accepted by the study population, DBS can be the preferred technique to efficiently obtain serum specimens for analyte testing.


Accumulation of an inactive form of p53 protein in cells treated with TNF alpha.
In MCF-7 cells, TNF alpha induces a G1 arrest with an increased expression of p21/Waf1, an activation of NF-kappa B and an accumulation of p53. NF-kappa B and p53 are two transcriptional factors known to activate p21/Waf1 gene expression. Here we show that p53 inhibition has no effect on p21/Waf1 mRNA accumulation following TNF alpha treatment. In contrast, inactivation of NF-kappa B inhibits p21/Waf1 expression without affecting G1 arrest. The fact that p21/Waf1 gene expression is still stimulated when p53 is inactivated strongly suggests that TNF alpha induces accumulation of an inactive form of p53 protein. This assumption was further supported by the following observations: (i) the p53 DNA-binding activity to its consensus sequence was not stimulated following TNF alpha treatment, (ii) phosphorylation at Ser-15, -20 or -392 was not detected in response to TNF alpha, (iii) the transcription rate of Ddb2, another p53 target gene, was not stimulated by TNF alpha. Finally, the accumulation of p53 in the nuclei of TNF alpha-treated MCF-7 cells was concomitant with an increase in p53 mRNA level, suggesting a regulation at the transcription level.


Computational decompression models.
Early computational models for decompression are based on supersaturation assumptions for dissolved gases. Such models, and our understanding of decompression biophysics, have been extended in the past 20 years by analyses of phase separation of gases. Generally termed thermodynamic decompression (or phase equilibration), these studies postulate a continuous exchange of inert gas between tissues and nucleation sites (gas micropockets), consistent with many commonplace phenomena. Postulates lead to decompression schedules and transfer mechanisms that differ from their earlier predecessors. The precise physical and computational bases supporting both viewpoints are described and contrasted.


Shared surname enhances our preference to famous people: multimodal EEG evidence.
Multimodal Electroencephalography techniques were used to determine whether the name of famous people undergoes self-relevant processing due to a shared surname with participants. During a three-stimulus oddball task, brain activity was recorded when participants suddenly saw their own names (self-name [SN]), a famous name with the same surname (FNS), or a famous name with a different surname (FND). While familiarity ratings were kept similar across the three kinds of name, behavioral analysis showed a higher rating on self-relevance for SN than for FNS, which, in turn, received a higher rating than FND. P2 amplitudes demonstrated a similar enhancement in response to SN and FNS compared to FND while P3 amplitudes and power of theta band (3.5-6 Hz) oscillation were more pronounced in response to SN than to FNS, which in turn elicited larger P3 and theta activities than FND. These findings, excluding the influence of familiarity, revealed that famous people sharing same surname with us could elicit a reliable self-relevant effect, despite lack of real social connection. This self-relevant processing may be embodied by the P3 amplitude and theta band neural oscillation in EEG.


Adenovirus-mediated p53 gene transfer suppresses growth of human glioblastoma cells in vitro and in vivo.
Alterations in the p53 tumor-suppressor gene occur in 35-60% of human glioblastomas, and re-introduction of p53 can suppress neoplastic growth. To evaluate the potential for p53 gene therapy of glioblastoma, we have analyzed the response of human glioblastoma cell lines in vitro and in vivo to experimental therapy with replication-deficient recombinant adenoviruses encoding wild-type p53 (rAd-p53). Western blot analyses showed high-level expression of p53 protein after treatment with rAd-p53, and transgene expression was dependent on promoter strength. A p53-specific dose-dependent inhibition of in vitro cellular proliferation was observed in 5 of 6 cell lines, and growth inhibition corresponded to adenovirus-mediated gene transfer and expression. p53-specific cell death was quantitated by release of the lactate dehydrogenase enzyme. Fragmentation of DNA into nucleosomal oligomers and the occurrence of a hypodiploid cell population detected by flow cytometry provided evidence for apoptosis. Studies in nude mice demonstrated that ex vivo infection with rAd-p53 suppressed the tumorigenic potential of human glioblastoma cells. Furthermore, direct injection of rAd-p53 into established s.c. xenografts inhibited tumor growth. Our observations suggest that re-introduction of wild-type p53 may have potential clinical utility for gene therapy of glioblastoma.


Effects of Grazing and Fire Frequency on Floristic Quality and its Relationship to Indicators of Soil Quality in Tallgrass Prairie.
Fire and grazing are widely used to manage grasslands for conservation purposes, but few studies have evaluated the effects of these drivers on the conservation value of plant communities measured by the floristic quality index (FQI). Further, the influence of fire and grazing on soil properties and functions are difficult for land managers and restoration practitioners to assess. The objectives of this study were to: (1) quantify the independent and interactive effects of grazing and fire frequency on floristic quality in native tallgrass prairie to provide potential benchmarks for community assessment, and (2) to explore whether floristic quality can serve as an indicator of soil structure and function for more holistic ecosystem assessments. A factorial combination of fire frequencies (1-2, 4, and 20 years return intervals) and grazing (by bison or ungrazed) treatments were sampled for plant species composition, and for several indicators of soil quality in lowland tallgrass prairie. Floristic quality, diversity, and richness were higher in grazed than ungrazed prairie over all fire frequencies (P < 0.05). Available inorganic N, microbial biomass N, total N, and soil bulk density were also higher in grazed prairie soil over all fire frequencies (P < 0.05). Microbial biomass C, total organic C, and total soil N were positively correlated with FQI (P < 0.05). This study shows that floristic quality and soil N pools are more strongly influenced by grazing than fire and that floristic quality can be an indicator of total soil C and N stocks in never cultivated lowland prairie.


Longitudinal changes in the disability level of the elders with low back pain after auriculotherapy.
To evaluate the longitudinal changes in the disability level of elders with LBP after receiving auriculotherapy. Randomized controlled trial. Sixty participants who were 60 years old or above and who were suffering from LBP were recruited from five hostels for the elders in Hong Kong. The participants were randomly allocated to receive a 3-week session of auriculotherapy using either semen vaccariae (control group=30) or magnetic pellets (experimental group=30). Seven auricular acupoints that are expected to have an effect on LBP were selected. Assessment data were collected at five points of time: (i) baseline, (ii) about 1.5 weeks of treatment, (iii) 3 weeks of treatment, (iv) 2 weeks post-treatment, and (v) 4 weeks post-treatment using the modified Aberdeen low back pain disability scale (Chinese). When the rate of change was compared between the two groups at each point of time starting from the baseline, those in the experimental group demonstrated significant improvement in the overall disability level, pain/sensation, and physical and functional abilities at 1.5 weeks of treatment (p<0.001), 3 weeks of treatment (p<0.001), 2 weeks post-treatment (p<0.001), and 4 weeks post-treatment (p<0.001). Longitudinal changes in the improvement of disability level were found among the elders with low back pain after receiving auriculotherapy using magnetic pellets.


[Age aspects in etiology and pathogenesis of postoperative adhesive intestinal obstruction].
Based on the clinical observations and experiments on animals, the authors consider that in young growing organisms peritoneal adhesions are formed more rapidly and intensively than in adults. Moreover, children show a more rapid reverse development of postoperative adhesions.


Copper-catalyzed [1,2]-rearrangements of allylic iodides and aryl α-diazoacetates.
The [1,2]- and [2,3]-rearrangements of iodonium ylides are synthetically useful reactions for the generation of functionalized α-iodoesters. Allylic iodides are coupled with α-diazoesters in the presence of a copper catalyst and a ligand to generate iodonium ylides, which undergo metal-mediated rearrangements. By fine-tuning the structure of the ligand, we have reversed the regioselectivity of copper-catalyzed reactions of iodonium ylides from [2,3]- to [1,2]-rearrangements with the use of alternate bipyridine ligands. The preference for [1,2]-rearrangements was further improved by using bulky aryl α-diazoester substrates. Several α-iodoesters with a diverse range of functional groups were generated in good yields (up to 88% yield) and high regioselectivities (up to >95:5 regioisomeric ratio). A deuterium-labeled substrate was utilized to gain insight into the mechanism of the reaction.


Pre-clinical efficacy and dosing of an AAV8 vector expressing human methylmalonyl-CoA mutase in a murine model of methylmalonic acidemia (MMA).
We demonstrate that human methylmalonyl-CoA mutase (MUT), delivered using an AAV serotype 8 vector, rescues the lethal phenotype displayed by mice with MMA and provides long-term phenotypic correction. In addition to defining a lower limit of effective dosing, our studies establish that neither a species barrier to mitochondrial processing nor an apparent immune response to MUT limits the murine model as an experimental platform to test the efficacy of human gene therapy vectors for MMA.


The nasal valve: new insights on the static and dynamic NV with MR-imaging.
We assessed the static nasal valve angle with MR imaging in healthy subjects and evaluated the complex mechanism of nasal valve dynamics during physiologic and forced inspiration. In 17 healthy subjects, measurements of the static nasal valve angle were conducted on MR scans, using a TSE Axial T2-weighted sequence and a 3 mm slice thickness. The dynamic changes of nasal valve movement were detected using MR Cine-imaging techniques. The static median angle of the nasal valve was found to be 28.6° with a range of 12.7°-39.3°. The median degree of nasal valve collapse during forced inspiration was 68% (range 20-99%) of the baseline (static nasal valve angle). In the moderately forced inspiration (3 s) the median nasal valve angle declined to 76% of the baseline angle (range 42-100%). In the physiologic or unforced inspiration, the median nasal valve angle was reduced to 86.3% of the baseline angle (range 52-100%). MRI, as a non-invasive tool, is a reliable method for evaluation of the static nasal valve angle and for the illustration of the complex nasal valve dynamics.


Genotypic distribution at the limits to natural and artificial selection with mutation.
A general procedure for analysing the change of genotypic distributions under stabilizing and truncation selection is described here and used to investigate the genotypic distribution at the limits to selection. For comparison, a simple approximate procedure using a normal distribution is also presented. It is clear that in the long term truncation introduces departures from normality mainly through gene frequency change, rather than through the generation of linkage disequilibrium under random mating. The Gaussian approximation performs reasonably well for additive gene effects unless the mean gene frequency is very extreme (say, outside the range of 0.05 to 0.95) and the number of loci is small (say, less then 50) regardless of the type of selection in operation. The genotypic distribution at the limits to selection largely depends on the type of limit reached. If a limit is obtained due to the action of natural selection before the exhaustion of existing variation, the distribution will normally not be very skew, but if a limit is reached at which mutation plays a central role in the maintenance of genetic variability, it could have high coefficients of skewness and kurtosis. The role of mutation on the long-term response is also discussed.


Middle cerebral artery stenosis is a major clinical determinant in striatocapsular small, deep infarction.
The significance of the stenotic lesions of the middle cerebral artery (MCA) in Asian patients with striatocapsular small, deep infarctions (SSDIs) remains undetermined. To investigate the frequency of stenotic lesions of the MCA in patients with SSDIs and to evaluate clinical and radiological features in those same patients. Acute stroke registry of a university hospital. One hundred two Korean patients with acute symptomatic SSDIs underwent cerebral angiography or magnetic resonance angiography and echocardiography. We divided these patients into 2 groups-patients with and without MCA occlusive lesions. The clinical and magnetic resonance image features were compared between these 2 groups. Thirty-seven patients (36%) had an ipsilateral proximal MCA lesion, whereas 65 patients (64%) showed no MCA abnormality on cerebral angiography or magnetic resonance angiography. Among 65 patients without an MCA lesion, 18 had an embolic source; the remaining 37 patients had no demonstrable embolic source. There were significant differences in the temporal profile and magnetic resonance imaging findings between the groups. Although the type of lacunar syndrome and the volume of infarcts did not differ between the groups, the unstable temporal profile and magnetic resonance imaging findings of multiple small infarcts in the symptomatic hemisphere were frequently observed in patients with MCA lesions. The proximal MCA lesion was a common cause of SSDIs in Korean patients. Depending on the existence of an MCA lesion, the clinical course and magnetic resonance imaging feature of the patients with SSDIs were different.


Characterisation of dihydroazulene and vinylheptafulvene derivatives using Raman spectroscopy: The CN-stretching region.
The effect of adding electron donating and withdrawing groups on the dihydroazulene (DHA)/vinylheptafulvene (VHF) photochromic system has been investigated using Raman spectroscopy in CS2 solutions. The photoswitching between DHA and VHF is often characterised with UV-Vis spectroscopy. However, Raman spectroscopy can also be used for this purpose and give structural insight, as the light induced ring-opening from DHA to VHF causes changes in the CN-stretching frequencies. The CN-stretching frequencies in DHA and VHF are isolated and optimal for the identification of DHA and VHF. The DHA system is also investigated in the solid state.


High serum Aspartate transaminase levels on day 3 postliver transplantation correlates with graft and patient survival and would be a valid surrogate for outcome in liver transplantation clinical trials.
Aspartate transaminase, a liver specific enzyme released into serum following acute liver injury, is used in experimental organ preservation studies as a measure of liver IR injury. Whether post-operative serum transaminases are a good indicator of IR injury and subsequent graft and patient survival in human liver transplantation remains controversial. A single centre prospectively collected liver transplant database was analysed for the period 1988-2012. All patients were followed up for 5 years or until graft failure. Transaminase levels on the 1st, 3rd and 7th post-operative days were correlated with the patient demographics, operative outcomes, post-operative complications and both graft and patient survival via a binary logistic regression analysis. Graft and patient survival at 3 months was 80.3% and 87.5%. AST levels on the 3rd (P = 0.005) and 7th (P = 0.001) post-operative days correlated with early graft loss. Patients were grouped by their AST level (day 3): <107iU, 107-1213iU, 1213-2744iU and >2744iU. The incidence of graft loss at 3 months was 10%, 12%. 27% and 59% and 1-year patient mortality was 12%, 14%, 27% and 62%. Day 3 AST levels correlate with patient and graft outcome post-liver transplantation and would be a suitable surrogate endpoint for clinical trials in liver transplantation.


Treatment of pediatric bilateral condylar fractures: A comprehensive analysis.
Pediatric bilateral condylar fractures (PBCF) is a rare clinical pathology, where the management is carried out with both conservative and surgical approaches. The purpose of this study was to analyze and compare these two treatment approaches and their associated long term complications in PBCF. An extensive literature review- through the search of online databases- was conducted to survey, collect, analyze and compare the reported outcomes of different treatment modalities for PBCF. The number of studies presenting PBCF case reports was 16, while the number of such retrospective studies included here was 19. Analyses of these studies revealed that the conservative treatment is preferred in PBCF patients younger than 12 years of age. Moreover, a composite approach where the open reduction and internal fixation (ORIF) is carried out for one side while the intermaxillary fixation (IMF) for the contralateral side is frequently reported for the management of PBCF cases; this approach appears effective in improving daily functioning of temporomandibular joint and reducing long term complications. Performing ORIF for one side while IMF for the contralateral side seems the most common treatment approach in PBCF. This study may help in rapid decision making for treatment selection of PBCF patients while minimizing the risk for late complications.


Hypolipidemic activity of P-methoxycinnamic diester (PCO-C) isolated from Copernicia prunífera against Triton WR-1339 and hyperlipidemic diet in mice.
Carnauba wax is extracted from the leaves of the Copernicia prunífera and contains approximately 80% of esters in its composition. The purpose of the present study was evaluate the hypolipidemic effect of p-methoxycinnamic diesters (PCO-C) extracted from Copernicia prunífera in a model of acute and chronic dyslipidemia in mice. The levels of total cholesterol and triglycerides were significantly reduced plasma levels in PCO-C at the dose of 100mg/kg in a model of acute and chronic dyslipidemia. Histological studies showed that PCO-C has no hepatotoxic effect and reduces hepatic steatosis in animals that consumed hyperlipidemic ration. Thus, it was concluded that PCO-C isolated from Copernicia Prunifera was effective in reducing total cholesterol and triglyceride levels in both dyslipidemia induction models. The finding indicates that PCO-C might be beneficial in treatment of hyperlipidemia and atherosclerosis.


Efficacy of immune checkpoint inhibitors in patients with anorectal melanoma in association with immune-related adverse events: a case series.
Anorectal melanoma (AM) is a rare subtype of mucosal melanoma with a poor prognosis. Given its rarity compared to its cutaneous counterpart, the benefits and side effects of immune checkpoint inhibitor (ICI) therapy and the relationship between side effects and prognosis remain unclear. Herein, we describe the clinical presentation of five patients with AM treated with ICI as well as their relationship to the treatment course and the development of immune-related adverse events (irAEs). Three patients received sequential or concurrent administrations of nivolumab and ipilimumab, one received nivolumab alone, and one received ipilimumab alone. The response rate (RR) and disease control rate (DCR) were 40% and 80%, respectively. Pituitary and hepatic dysfunctions were the most common irAEs observed (40% each), followed by thyroid, diarrhea, and renal dysfunctions (20% each). The RR was 67% in patients with irAEs while no response was observed in patients without irAEs. DCR was 100% and 50% in patients with and without irAEs, respectively. Overall survival was 34 months in irAE and 8.75 months in non-irAE cases, with a longer survival trend in irAE cases. ICI therapy was effective and well-tolerated by AM patients, with potentially better outcomes for those who experienced irAEs compared to those who did not.


Apparent inconsistent theophylline absorption from sustained release capsules.
Sustained release theophylline products can improve compliance and symptom control in children with asthma. This study examines theophylline serum concentration monitoring in pediatric patients. Fifteen children with documented asthma were randomized to receive either Slo-bid Gyrocaps or Theo-dur Sprinkle for 1 month, and then crossed over to the other product. On the last day of each study period, theophylline serum concentrations were obtained prior to the morning dose and 4 hours later. In two patients receiving Theo-dur Sprinkle and six with Slo-bid Gyrocaps, the 4-hour serum concentration was lower than the pre-dose concentration. The change between the pre-dose and post-dose serum concentrations for Theo-dur Sprinkle ranged from a decrease of 2.8 mg/L to an increase of 4.9 mg/L, and, for Slo-bid Gyrocaps, from a decrease of 4.6 mg/L to an increase of 10.5 mg/L. The inconsistent theophylline absorption with each product makes dosage adjustment difficult.