Antihypertensive treatment and serum cholesterol: results of population-based surveys in the German Cardiovascular Prevention Study.
We analyzed the data from three cross-sectional, population-based surveys in West Germany to evaluate the effect of antihypertensive drug therapy on the level of serum cholesterol in German residents (18,344 males; 19,137 females) aged 25-69 years, after excluding persons with missing values (N = 5529) for any study variable. The data were obtained from the national and regional health surveys that were conducted during the years 1984-1992, within the framework of the German Cardiovascular Prevention Study (GCP). The response rates were between 66.0% and 71.4% for the national surveys and between 65.9% and 83.3% for the regional surveys. Blood-pressure and non-fasting cholesterol measurements were carried out under strictly standardized conditions. Multiple linear regression analysis was used to compare the age-adjusted mean value and prevalence for each of the following study variables: total serum cholesterol, HDL-cholesterol, non-HDL cholesterol, and the ratio of HDL cholesterol/total cholesterol for users and non-users of antihypertensive medications. Antihypertensive medications were reportedly taken during the seven days preceding the survey examination by 7.8% of all males and 10.4% of all females. The beta-blocker type of medication was prescribed most frequently for lowering high blood pressure. In both genders, the strongest age-adjusted effect of an increase in cholesterol level was found for beta-blockers. The difference in the age-adjusted means for non-HDL cholesterol values between users and non-users of beta-blockers was 9.2 mg/dL (p < 0.001) in males and 9.0 mg/dL (p < 0.001) in females. Regression analysis carried out to control for several potential confounders confirmed the results. The findings suggest that mass treatment of hypertension with beta-blockers may be associated with reductions in benefit because of an increase in non-HDL and a decrease in HDL cholesterol levels.


Transcriptomes and DNA methylomes in apomictic cells delineate nucellar embryogenesis initiation in citrus.
Citrus nucellar poly-embryony (NPE) is a mode of sporophytic apomixis that asexual embryos formed in the seed through adventitious embryogenesis from the somatic nucellar cells. NPE allows clonal propagation of rootstocks, but it impedes citrus cross breeding. To understand the cellular processes involved in NPE initiation, we profiled the transcriptomes and DNA methylomes in laser microdissection captured citrus apomictic cells. In apomictic cells, ribosome biogenesis and protein degradation were activated, whereas auxin polar transport was repressed. Reactive oxygen species (ROS) accumulated in the poly-embryonic ovules, and response to oxidative stress was provoked. The global DNA methylation level, especially that of CHH context, was decreased, whereas the methylation level of the NPE-controlling key gene CitRWP was increased. A C2H2 domain-containing transcription factor gene and CitRWP co-expressed specifically in apomictic cells may coordinate to initiate NPE. The activated embryogenic development and callose deposition processes indicated embryogenic fate of nucellar embryo initial (NEI) cells. In our working model for citrus NPE initiation, DNA hyper-methylation may activate transcription of CitRWP, which increases C2H2 expression and ROS accumulation, triggers epigenetic regulation and regulates cell fate transition and NEI cell identity in the apomictic cells.


Promoting Behavioral Change in Psychoanalytic Treatments.
One of the shibboleths of psychoanalysis is that treatment should not target behavioral change, focusing instead on gaining insight and the therapeutic relationship (Freud, 1917; 1923; Gabbard, 2014; Greenson, 1967). Such an approach is believed to be accompanied by disruptions of exploration or problematic distortions of the transference (Freud, 1917; 1923; Gabbard, 2014; Greenson, 1967). However, ignoring behavioral change can put patients at increased risk for stalemates in treatment and persistent problematic behaviors that interfere with improvement and impair relationships. This article suggests that rather than being at odds or disruptive, efforts at behavioral change can be part of the development and employment of a psychodynamic formulation, and can be used to enhance self-understanding and exploration of the transference. Psychoanalytic approaches provide strategies for behavioral change not included in other psychotherapeutic treatments. This article describes a variety of ways in which efforts at behavioral change can be integrated with and enhanced by psychodynamic exploration.


Cost effectiveness of vaccination against pneumococcal pneumonia: an update.
We updated a 1978 cost-effectiveness analysis of vaccination against pneumococcal pneumonia in light of the introduction in 1983 of a 23-valent vaccine, recent medical literature, and different relative prices of medical services. Although other base-case assumptions have remained reasonable, the low estimates of 10% of pneumonia as pneumococcal and a 3-year duration of immunity now appear more likely. Vaccination of a person age 65 or older could gain a year of healthy life for about $6000 in 1983 dollars. Medicare has covered pneumococcal vaccination since 1981. With the revised assumptions, net Medicare expenditures ranged from about $5.50 to $10.50 per vaccination, or from $4400 to $8300 per year of healthy life gained. Vaccination of an elderly person would almost break even, if duration of immunity were 8 years and would be cost saving if the vaccine were administered under a public program. Current levels of vaccination appear too low considering the potential health benefits and cost-effectiveness.


Targeting the stroma by T cells to limit tumor growth.
Solid tumors may modulate their environment and keep stromal cells in an immunosuppressive and tumor-promoting state. Recent findings indicate that targeting not only cancer cells but also nonmalignant stromal cells by T cells is required for the eradication of established tumor. Interestingly, a single adoptive transfer of effector T cells that recognize tumor antigen-loaded stromal cells, but not the cancer cells themselves, causes long-term inhibition of tumor growth associated with T cell-mediated killing of stromal CD11b+/Gr1+ myeloid cells. Therefore, targeting tumor stroma by T cells points to an important alternative approach to the effective control of tumor growth, particularly in the absence of direct targeting of cancer cells.


The effect of rosiglitazone in the prevention of intra-abdominal adhesion formation in a rat uterine horn model.
Effects of rosiglitazone in the prevention of adhesion formation were evaluated. Eighty Wistar albino rats were randomly grouped into eight equally sized groups. A 2-cm segment of the antimesenteric surface of the right uterine horn was traumatized to form a standardized lesion, using bipolar cautery. A dose-response study was performed with 0.1, 0.3, 1 and 3 mg/kg/day rosiglitazone. Fifteen days later, adhesions were evaluated clinically and histopathologically. A time-response study was performed with 1 mg/kg/day rosiglitazone (the minimum dose found to significantly affect adhesion formation). Rosiglitazone was given for 7 days post-operatively and results were compared with those of control and the 15-day group (time-response). In all these studies, rosiglitazone was orally administered 3 days before the operation and continued post-operatively. In two further experimental groups, rosiglitazone was only administered pre-operatively or post-operatively. Approximately 1 mg/kg/day rosiglitazone was found to reduce adhesion scores both clinically and histopathologically. Duration of treatment was also found to affect the extent of adhesion formation. However, giving rosiglitazone either just pre-operatively or post-operatively did not significantly reduce adhesion formation. Rosiglitazone with peroxisome proliferator-activated receptor (PPAR)-gamma agonist activity reduced the formation of i.p. adhesion possibly by reducing the initial inflammatory response and the subsequent exudation in this study.


Identification of Genomic Species of Acinetobacter Isolated from Burns of ICU Patients.
The worldwide emergence of multi-drug resistant (MDR) bacteria in recent years has caused many problems for hospitals and patients, especially intensive care unit patients. Among these clinically important MDR bacteria are Acinetobacter baumannii complex species (A. baumannii, Acinetobacter genomic species 3 and Acinetobacter genomic species 13TU) that cause a wide range of infections. The sequencing and bioinformatics analysis of a part of the Zone 1 of rpoB gene was performed for species identification of Acinetobacter isolates obtained from ICU patients with infected burns hospitalized in a hospital in Isfahan, Iran, over a 9-month period. Antibiotic sensitivity of Acinetobacter isolates was investigated using the disk diffusion method and different classes of antibiotics including amikacin, cefotaxime, ceftriaxone, ciprofloxacin, imipenem and piperacillin. Acinetobacter spp. were isolated from 10 of 80 (12.5%) investigated patients. All of the 10 Acinetobacter isolates were identified as Acinetobacter baumannii and multi-drug resistant according to antibiotic susceptibility tests. Of the Acinetobacter baumannii complex members, only A. baumannii species was identified among the isolates obtained from patients with infected burns in an Isfahan hospital over a 9-month period.


Conformation state-specific monobodies regulate the functions of flexible proteins through conformation trapping.
Synthetic binding proteins have emerged as modulators of protein functions through protein-protein interactions (PPIs). Because PPIs are influenced by the structural dynamics of targeted proteins, investigating whether the synthetic-binders-based strategy is applicable for proteins with large conformational changes is important. This study demonstrates the applicability of monobodies (fibronectin type-III domain-based synthetic binding proteins) in regulating the functions of proteins that undergo tens-of-angstroms-scale conformational changes, using an example of the A55C/C77S/V169C triple mutant (Adktm ; a phosphoryl transfer-catalyzing enzyme with a conformational change between OPEN/CLOSED forms). Phage display successfully developed monobodies that recognize the OPEN form (substrate-unbound form), but not the CLOSED form of Adktm . Two OPEN form-specific clones (OP-2 and OP-4) inhibited Adktm kinase activity. Epitope mapping with a yeast-surface display/flow cytometry indicated that OP-2 binds to the substrate-entry side of Adktm , whereas OP-4 binding occurs at another site. Small angle X-ray scattering coupled with size-exclusion chromatography (SEC-SAXS) indicated that OP-4 binds to the hinge side opposite to the substrate-binding site of Adktm , retaining the whole OPEN-form structure of Adktm . Titration of the OP-4-Adktm complex with Ap5 A, a transition-state analog of Adktm , showed that the conformational shift to the CLOSED form was suppressed although Adktm retained the OPEN-form (i.e., substrate-binding ready form). These results show that OP-4 captures and stabilizes the OPEN-form state, thereby affecting the hinge motion. These experimental results indicate that monobody-based modulators can regulate the functions of proteins that show tens-of-angstroms-scale conformational changes, by trapping specific conformational states generated during large conformational change process that is essential for function exertion.


High-Purity Inorganic Perovskite Films for Solar Cells with 9.72 % Efficiency.
All-inorganic perovskite solar cells with high efficiency and improved stability are promising for commercialization. A multistep solution-processing method was developed to fabricate high-purity inorganic CsPbBr3 perovskite films for use in efficient solar cells. By tuning the number of deposition cycles (n) of a CsBr solution, the phase conversion from CsPb2 Br5 (n ≤3), to CsPbBr3 (n=4), and Cs4 PbBr6 (n≥5) was optimized to achieve vertical- and monolayer-aligned grains. Upon interfacial modification with graphene quantum dots, the all-inorganic perovskite solar cell (without a hole-transporting layer) achieved a power conversion efficiency (PCE) as high as 9.72 % under standard solar illumination conditions. Under challenging conditions, such as 90 % relative humidity (RH) at 25 °C or 80 °C at zero humidity, the optimized device retained 87 % PCE over 130 days or 95 % over 40 days, compared to the initial efficiency.


Effects of combinations of 7beta-hydroxycholesterol and anticancer drugs or ionizing radiation on the proliferation of cultured tumor cells.
Oxysterols compose a large class of natural substances endowed in a number of cases with marked antiproliferative and cytotoxic activities. The consequences of treatments combining 7beta-hydroxycholesterol (7beta-OHC) or XG-142 (a galactose-linked hydrosoluble derivative of 7beta-OHC) with drugs used in cancer chemotherapy or gamma radiation has been evaluated upon a variety of tumor cell lines: Hep-G2, U937, K562 cells, its adriamycin-resistant variant K562 Adr+ and RDM4. Proliferation was assessed by the Uptiblue assay and the [3H]Thymidine incorporation test. Results indicated that 7beta-OHC increased the sensitivity of tumor cells to adriamycin, VP-16, 5-FU and bleomycin to various degrees. 7beta-OHC was found to reinforce the susceptibility of K562 adriamycin-resistant cells to this drug. In RDM4 cells, an enhanced radiosensitivity by 7beta-OHC was also obtained, whereas XG-142 was less efficient in provoking such an effect.


Persistent cerebrovascular damage after stroke in type two diabetic rats measured by magnetic resonance imaging.
Diabetes mellitus is a disease with vascular components. Consequently, the blood-brain barrier disruption after stroke may differ between diabetic and nondiabetic animals. However, few studies have documented the longitudinal blood-brain barrier disruption afte stroke in diabetic animals. In this study, using MRI, we noninvasively evaluated the blood-brain barrier damage after middle cerebral artery occlusion in diabetic and nondiabetic rats. Type 2 diabetes mellitus (T2DM) was induced in adult male Wistar rats by administration of a high-fat diet in combination with a single intraperitoneal injection (35 mg/kg) of streptozotocin. T2DM rats (n=9) and nondiabetic wild-type (WT) rats (n=9) were subjected to middle cerebral artery occlusion for 2 hours using the filament model. MRI was performed 1 day and then weekly for 5 weeks after middle cerebral artery occlusion for all rats. The ischemic lesion volumes after stroke as measured using T2 maps were not significantly different between the T2DM and WT rats. Compared with the WT rats, the volumes of blood-brain barrier disruption evaluated using contrast-enhanced T1-weighted imaging with gadolinium-diethylenetriamine penta-acetic acid and the cerebral hemorrhagic volumes measured with susceptibility-weighted imaging were significantly (P<0.05) larger in the T2DM rats from 1 to 5 weeks after stroke; values of diffusion fractional anisotropy were significantly lower in T2DM rats (P<0.03) than in WT rats after stroke. These MRI measurements were consistent with histological data. Using MRI, T2-weighted imaging did not detect significant differences of the ischemic lesion volumes between T2DM and WT rats. In contrast to the WT rats, however, contrast-enhanced T1-weighted imaging and susceptibility-weighted imaging identified much more severe ischemic vascular damage, whereas fractional anisotropy demonstrated lower axonal density in the T2DM rats after stroke.


Unilateral dorsiflexor strengthening with mirror therapy to improve motor function after stroke: A pilot randomized study.
Independently, cross-education, the performance improvement of the untrained limb following unilateral training, and mirror therapy have shown to improve lower limb functioning poststroke. Mirror therapy has shown to augment the cross-education effect in healthy populations. However, this concept has not yet been explored in a clinical setting. This study set out to investigate the feasibility and potential efficacy of applying cross-education combined with mirror therapy compared with cross-education alone for lower limb recovery poststroke. Thirty-one chronic stroke participants (age 61.7 ± 13.3) completed either a unilateral strength training (ST; n = 15) or unilateral strength training with mirror-therapy (MST; n = 16) intervention. Both groups isometrically strength trained the less-affected ankle dorsiflexors three times per week for 4 weeks. Only the MST group observed the mirror reflection of the training limb. Patient eligibility, compliance, treatment reliability, and outcome measures were assessed for feasibility. Maximal voluntary contraction (MVC; peak torque, rate of torque development, and average torque), 10-m walk test, timed up and go (TUG), Modified Ashworth Scale (MAS), and the London Handicap Scale (LHS) were assessed at pretraining and posttraining. Treatment and assessments were well tolerated without adverse effects. No between group differences were identified for improvement in MVC, MAS, TUG, or LHS. Only the combined treatment was associated with functional improvements with the MST group showing an increase in walking velocity. Cross-education plus mirror therapy may have potential for improving motor function after stroke. This study demonstrates the feasibility of the combination treatment and the need for future studies with larger sample sizes to investigate the effectiveness of the treatment.


The 1918 influenza epidemic in Mamre.
The 1918 influenza epidemic was a historic, health and demographic landmark in South Africa. In Mamre the mortality rate was 39/1,000, which was similar to the rate in Cape Town. The male/female ratio was 1,33, with males between the ages of 20 and 40 years accounting for 60% of deaths.


Gastroscopy: a primary diagnostic procedure.
EGD, using 1986 models of either the fiberoptic gastroscope or the videoscope, is a safe and accurate procedure that can be performed by any physician trained in the technique of endoscope passage. It may be performed at large medical centers or small rural hospitals, outpatient clinics, or even private offices. Patients themselves have indicated preference for endoscopic evaluation over the double-contrast barium meal after they have experienced both procedures. The short time of procedure, its accuracy, safety, and its relative lack of discomfort to the patient lend it readily to being an initial component in the primary evaluation of symptoms of abdominal distress, gastrointestinal bleeding, dysphagia, esophageal reflux, persistent vomiting, and odynophagia. It is essential in the evaluation of complications of esophageal reflux and the evaluation of abnormal radiological findings in the upper gastrointestinal tract. It should never be overlooked in evaluating the patient with iron deficiency anemia of unknown etiology. Economic pressures have already moved EGD from the surgery wards to endoscopy labs and to the outpatient setting. These same forces will project more physicians into the role of the diagnostic endoscopist and the patient will benefit by decreased medical costs, quicker diagnosis and treatment, and enhanced continuity of care.


UV-B-type mutations and chromosomal imbalances indicate common pathways for the development of Merkel and skin squamous cell carcinomas.
Two developmentally highly divergent nonmelanoma skin cancers, the epidermal squamous cell carcinomas (SCC) and the neuroendocrine Merkel cell carcinomas (MCC), occur late in life at sun-exposed body sites. To determine whether these similarities may indicate common genetic alterations, we studied the genetic profile of 10 MCCs and analyzed 6 derived cell lines and 5 skin SCC lines by comparative genomic hybridization (CGH) and molecular genetic analyses. Although the MCCs were highly divergent-only 3 of the 10 tumors exhibited common gains and losses-they shared gain of 8q21-q22 and loss of 4p15-pter with the genetically much more homogeneous SCC lines. In addition, 2 of 5 SCC and 2 of 6 MCC lines exhibited UV-B-type-specific mutations in the p53 tumor-suppressor gene and a high frequency (9/11) of CC-->TT double base changes in codon 27 of the Harvey (Ha)-ras gene. Since 45% of the tumor lines were homozygous for this nucleotide substitution compared to 14% of the controls and in 1 MCC patient the wild-type allele was lost in the tumor, this novel polymorphism may contribute to tumor development. On the other hand, loss of 3p, characteristic for SCCs, was rare in MCCs. Although in 2 of 3 SCC lines 3p loss was correlated with reduced expression of the FHIT (fragile histidine triad) gene, the potential tumor suppressor mapped to 3p14.2 and 2 MCC lines with normal 3p showed aberrant or no FHIT transcripts. Taken together, in addition to the common UV-B-specific mutations in the p53 and Ha-ras gene, MCCs and SCCs also share chromosomal imbalances that may point to a common environmental-derived (e.g., UV-A) oxidative damage.


Diagnosis and management of the primary hydatidiform mole.
Hydatidiform mole may be categorized as either complete or partial on the basis of gross morphology, histology, and karyotype. The diagnosis, natural history, and management of patients with complete and partial moles are reviewed in detail. The controversy concerning chemoprophylaxis at the time of molar evacuation is also discussed. Furthermore, subsequent reproductive outcome in patients with both complete and partial moles is analyzed.


Tissue-aware data integration approach for the inference of pathway interactions in metazoan organisms.
Leveraging the large compendium of genomic data to predict biomedical pathways and specific mechanisms of protein interactions genome-wide in metazoan organisms has been challenging. In contrast to unicellular organisms, biological and technical variation originating from diverse tissues and cell-lineages is often the largest source of variation in metazoan data compendia. Therefore, a new computational strategy accounting for the tissue heterogeneity in the functional genomic data is needed to accurately translate the vast amount of human genomic data into specific interaction-level hypotheses. We developed an integrated, scalable strategy for inferring multiple human gene interaction types that takes advantage of data from diverse tissue and cell-lineage origins. Our approach specifically predicts both the presence of a functional association and also the most likely interaction type among human genes or its protein products on a whole-genome scale. We demonstrate that directly incorporating tissue contextual information improves the accuracy of our predictions, and further, that such genome-wide results can be used to significantly refine regulatory interactions from primary experimental datasets (e.g. ChIP-Seq, mass spectrometry). An interactive website hosting all of our interaction predictions is publically available at http://pathwaynet.princeton.edu. Software was implemented using the open-source Sleipnir library, which is available for download at https://bitbucket.org/libsleipnir/libsleipnir.bitbucket.org. Supplementary data are available at Bioinformatics online.


Dichotomous flow with thermal diffusion and stochastic resetting.
We consider properties of one-dimensional diffusive dichotomous flow and discuss effects of stochastic resonant activation (SRA) in the presence of a statistically independent random resetting mechanism. Resonant activation and stochastic resetting are two similar effects, as both of them can optimize the noise-induced escape. Our studies show completely different origins of optimization in adapted setups. Efficiency of stochastic resetting relies on elimination of suboptimal trajectories, while SRA is associated with matching of time scales in the dynamic environment. Consequently, both effects can be easily tracked by studying their asymptotic properties. Finally, we show that stochastic resetting cannot be easily used to further optimize the SRA in symmetric setups.


Synthesis of beta-D-Glcp-(1-->3)-[beta-D-Glcp-(1-->6)]-beta-D-Glcp-(1-->3)-beta-D-Glcp-(1-->6)-[beta-D-Galp-(1-->4)-beta-D-Glcp-(1-->3)]-beta-D-GlcpOLauryl, an oligosaccharide with anti-tumor activity.
A concise and effective synthesis of lauryl heptasaccharide 17 was achieved from the key intermediates lauryl 2,3,4,6-tetra-O-benzoyl-beta-D-galactopyranosyl-(1-->4)-2,3,6-tri-O-benzoyl-beta-D-glucopyranosyl-(1-->3)-2,4-di-O-benzoyl-beta-D-glucopyranoside (10) and isopropyl 2,4,6-tri-O-acetyl-3-O-allyl-beta-D-glucopyranosyl-(1-->3)-[2,3,4,6-tetra-O-benzoyl-beta-D-glucopyranosyl-(1-->6)]-2,4-di-O-acetyl-beta-D-glucopyranosyl-(1-->3)-2,4,6-tri-O-acetyl-1-thio-beta-D-glucopyranoside (15). The key trisaccharide glycosyl acceptor 10 was constructed by coupling 2,3,4,6-tetra-O-benzoyl-beta-D-galactopyranosyl-(1-->4)-2,3,6-tri-O-benzoyl-alpha-D-glucopyranosyl trichloroacetimidate (3) with lauryl 6-O-acetyl-2,4-di-O-benzoyl-beta-D-glucopyranoside (9), followed by deacetylation. The thioglycoside donor 15 was obtained by condensation of 2,4,6-tri-O-acetyl-3-O-allyl-beta-D-glucopyranosyl-(1-->3)-[2,3,4,6-tetra-O-benzoyl-beta-D-glucopyranosyl-(1-->6)]-2,4-di-O-acetyl-alpha-D-glucopyranosyl trichloroacetimidate (11) with isopropyl 4,6-O-benzylidene-1-thio-beta-D-glucopyranoside (12), followed by debenzylidenation and acetylation. A bioassay of the inhibition of S180 noumenal tumors showed that lauryl heptasaccharide 17 could be employed as a potential agent for cancer treatment.


Synthesis and in vitro antioxidant activity study of some new piperazinyl flavone compounds.
Flavones exhibit a variety of beneficial effects and are well known for their medicinal importance in several diseases, including cardiovascular, neurodegenerative and cancer. The inclusion of the piperazine ring to the flavone backbone is an important strategy in drug discovery but only a few studies have synthesized piperazinyl flavone compounds to test their biological activity. While there is a major focus on the antioxidant properties of drugs in therapy of several diseases of inflammatory origin, we synthesized a series of the novel piperazinyl flavone analogues bearing the phenyl ring with different substituents. The analogues were evaluated for in vitro antioxidant activity against superoxide anion radical, hydroxyl radical, 2,2-diphenyl-1-picrylhydrazyl radical, and hydrogen peroxide scavenging properties. The total antioxidant status based on the absorbance of the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) radical cation (ABTS+• ) and total antioxidant capacity using the Fe(III)-ferrozine complex were also monitored. The results of the above studies showed that the compounds synthesized were found possessed moderate radical scavenging potential, and that their interaction with reactive oxygen species is complex and depends on their structural conformation and the type of substituent R in the piperazine ring being attached. Best antiradical activity were found for the compounds with methoxy groups on the phenyl ring of substituent R, whereas the presence of methoxy or trifluoromethyl groups in substituent R resulted in higher ABTS+• and ion Fe(III) reduction. These compounds are promising molecules to be used for their antioxidant properties and may be regarded, after improvement of the antioxidant potential, to control diseases of free radical etiology.


Teaching now, facing the future.
To obtain knowledge is not the purpose of education, but to develop one's potential ability and to obtain wisdom is. We are living in a fast changing world and knowledge is growing explosively. Therefore, what facts or information students have known in your class is not the most important thing. What really matters is how efficiently students could learn and how those knowledge they have learned can help them to deal with their own tasks in the future. This article introduces our four-dimensional comprehensive course design and the teaching activities we used to optimize and improve students' learning and developing process.


Influence of Alcohol Consumption on Body Mass Gain and Liver Antioxidant Defense in Adolescent Growing Male Rats.
The World Health Organization (WHO) reported that alcohol consumption is a serious problem in adolescents. The aim of the study was to assess the influence of the time of exposure of various alcoholic beverages on body mass as well as on select parameters of liver antioxidant defense in adolescent Wistar rats. Thirty-day-old animals were divided into 12 groups (six animals in each): control and groups receiving various beverages containing 10% of alcohol (ethanol, red wine, beer), observed for two, four, and six weeks. The body weight gain and energy supply were analyzed for body mass assessment. The catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase, transferase (GST), reductase activities, total antioxidant status, and glutathione level (GSH) were analyzed, for a liver antioxidant defense assessment. Group receiving red wine was characterized by the highest alcohol intake, lowest dietary intake, and highest total energy supply (p < 0.05). However, this did not influence body weight gain (p > 0.05). Reduced diet intake in groups receiving alcohol was counterbalanced by its energy value. Therefore, the energy supply was not lower than for the control (p > 0.05). Alcohol consumption and the experiment duration influenced CAT, SOD, and GST activities and GSH level. Alcohol consumption may influence hepatic antioxidant defense in adolescent male rats, but without influence on body weight gain.


Knowledge, attitude and practices of schoolteachers toward epilepsy and students with epilepsy.
This study aimed to estimate and evaluate teachers' knowledge, attitudes, and practices toward students with epilepsy and to determine the association between selected demographic factors. This cross-sectional study was approved by the ethical committee of King Saud University, Riyadh, Saudi Arabia. The study was conducted at the department of physiology, King Saud University, from October 2020 until October 2021. The data was collected through anonymous online self-administered 44-item questionnaires. The sampling technique used was Snowball sampling from ten randomly selected schools in Riyadh. The total sample size was 456 participants. The mean age of the respondents was 41.5 ± 8.52, and a male to female ratio of 1.4:1. The mean years of experience of the respondents is 16.14 ± 8.85. Almost all teachers knew that epilepsy is a neurological disorder (97.8%). However, females were more likely to know the cause of epilepsy (p=0.003). The majority of public-school teachers (80.2%) thought that epileptic students have normal intelligence (p=0.004). A considerable proportion of public-school teachers (82.8%) do not mind having a student with epilepsy in their classes (p=0.012). The vast majority of schoolteachers (95.4%) have not had any training on how to deal with an epileptic student during a seizure. This study shows that schoolteachers have very good knowledge about epilepsy but poor practice towards it. Well-directed training programs are needed to qualify teachers in providing first aid to epileptic students during seizures.


Expression of matrix metalloproteinase-9 correlates with poor prognosis in human malignant fibrous histiocytoma.
92 kDa matrix metalloproteinase-9 (MMP-9) is believed to play an important role in degrading the matrix and basement membrane, contributing to the invasion and metastasis of malignant solid tumors. However, little is known about its involvement in a malignant fibrous histiocytoma. The aim of this study was to investigate the expression of MMP-9 and to correlate its expression with clinicopathologic parameters in human malignant fibrous histiocytomas. Archival tumor tissues from 20 patients with a malignant fibrous histiocytoma were analyzed by immunohistochemistry for the expression of MMP-9. Clinical information was obtained through the computerized retrospective database from the tumor registry. Seventeen of 20 (85%) tumors showed a positive reaction for MMP-9. MMP-9 activity was inversely correlated with patients' survival time (p=.011). There was no significant correlation between the activated MMP-9 expression and all the other clinicopathologic variables. Our data demonstrate that MMP-9 activation is likely to occur in human malignant fibrous histiocytomas. It is also noteworthy that the expression of MMP-9 may aid in predicting patients' poor prognosis.


History of intranasal splints.
Intranasal splints have long been utilised as a post-operative adjunct in septoplasty, intended to reduce the risk of adhesions and haematoma formation, and to maintain alignment during healing. A Medline literature review of the history and evolution of intranasal splint materials and designs was performed. Advantages and disadvantages of various splints are discussed. Intranasal splints fashioned from X-ray film were first reported in 1955. Since then, a variety of materials have been utilised, including polyethylene coffee cup lids, samarium cobalt magnets and dental utility wax. Most contemporary splints are produced from silicon rubber or polytetrafluoroethylene (Teflon). Designs have varied in thickness, flexibility, shape, absorption and the inclusion of built-in airway tubes. Future directions in splint materials and designs are discussed. Intranasal splints have steadily evolved since 1955, with numerous novel innovations. Despite their simplicity, they play an important role in nasal surgery and will continue to evolve over time.


Perception of mind and dehumanization: Human, animal, or machine?
Dehumanization is reached through several approaches, including the attribute-based model of mind perception and the metaphor-based model of dehumanization. We performed two studies to find different (de)humanized images for three targets: Professional people, Evil people, and Lowest of the low. In Study 1, we examined dimensions of mind, expecting the last two categories to be dehumanized through denial of agency (Lowest of the low) or experience (Evil people), compared with humanized targets (Professional people). Study 2 aimed to distinguish these targets using metaphors. We predicted that Evil and Lowest of the low targets would suffer mechanistic and animalistic dehumanization, respectively; our predictions were confirmed, but the metaphor-based model nuanced these results: animalistic and mechanistic dehumanization were shown as overlapping rather than independent. Evil persons were perceived as "killing machines" and "predators." Finally, Lowest of the low were not animalized but considered human beings. We discuss possible interpretations.


ErbB2 receptor over-expression improves post-traumatic peripheral nerve regeneration in adult mice.
In a transgenic mice (BALB-neuT) over-expressing ErbB2 receptor, we investigated the adult mouse median nerve in physiological and pathological conditions. Results showed that, in physiological conditions, the grip function controlled by the median nerve in BALB-neuT mice was similar to wild-type (BALB/c). Stereological assessment of ErbB2-overexpressing intact nerves revealed no difference in number and size of myelinated fibers compared to wild-type mice. By contrast, after a nerve crush injury, the motor recovery was significantly faster in BALB-neuT compared to BALB/c mice. Moreover, stereological assessment revealed a significant higher number of regenerated myelinated fibers with a thinner axon and fiber diameter and myelin thickness in BALB-neuT mice. At day-2 post-injury, the level of the mRNAs coding for all the ErbB receptors and for the transmembrane (type III) Neuregulin 1 (NRG1) isoforms significantly decreased in both BALB/c and BALB-neuT mice, as shown by quantitative real time PCR. On the other hand, the level of the mRNAs coding for soluble NRG1 isoforms (type I/II, alpha and beta) increased at the same post-traumatic time point though, intriguingly, this response was significantly higher in BALB-neuT mice with respect to BALB/c mice. Altogether, these results suggest that constitutive ErbB2 receptor over-expression does not influence the physiological development of peripheral nerves, while it improves nerve regeneration following traumatic injury, possibly through the up-regulation of soluble NRG1 isoforms.


IL-6 ameliorates acute lung injury in influenza virus infection.
Interleukin 6 (IL-6) is involved in innate and adaptive immune responses to defend against pathogens. It also participates in the process of influenza infection by affecting viral clearance and immune cell responses. However, whether IL-6 impacts lung repair in influenza pathogenesis remains unclear. Here, we studied the role of IL-6 in acute influenza infection in mice. IL-6-deficient mice infected with influenza virus exhibited higher lethality, lost more body weight and had higher fibroblast accumulation and lower extracellular matrix (ECM) turnover in the lung than their wild-type counterparts. Deficiency in IL-6 enhanced proliferation, migration and survival of lung fibroblasts, as well as increased virus-induced apoptosis of lung epithelial cells. IL-6-deficient lung fibroblasts produced elevated levels of TGF-β, which may contribute to their survival. Furthermore, macrophage recruitment to the lung and phagocytic activities of macrophages during influenza infection were reduced in IL-6-deficient mice. Collectively, our results indicate that IL-6 is crucial for lung repair after influenza-induced lung injury through reducing fibroblast accumulation, promoting epithelial cell survival, increasing macrophage recruitment to the lung and enhancing phagocytosis of viruses by macrophages. This study suggests that IL-6 may be exploited for lung repair during influenza infection.


Impetigo Leishmaniasis Previously Diagnosed as Crusty Impetigo: A Case Study.
Cutaneous leishmaniasis is a zoonotic disease caused by several species of protozoa of the genus Leishmania. Cutaneous leishmaniasis classically presents as an ulcer with heaped edges, but it can also appear as nodular, scabbed, or plaque-like lesions. Its diagnosis requires confirmatory laboratory tests such as a smear, culture, and polymerase chain reaction. However, atypical presentations represent a diagnostic challenge in Tropical Medicine. For instance, localized cutaneous leishmaniasis (LCL) resembles bacterial and fungal tropical dermatological infections. Atypical presentations require an experienced clinician, epidemiological knowledge, and proper diagnostic tests. We present a case of a 10-year-old male who showed classic impetigo-like symptoms, which did not improve with topical or systemic antibiotic therapy. After a thorough case review, the patient was diagnosed with LCL. Therefore, epidemiological and clinical evaluation is crucial when diagnosing, especially in patients who live or have travelled to leishmaniasis-endemic areas.


[Behavior therapy technics in the treatment of endogenous eczema with special reference to compulsive scratching].
An exact observation and description of scratching behavior leads to a behavioral model for the obsessional scratching in patients with atopic dermatitis. The patient who cannot handle negative emotions because of a deficit in social behavior strategies suffers from diffuse tension. He can reduce the tension for the moment by scratching. Thus itching is being reinforced. The feeling of misbehavior occurs with delay and then again can serve as a stimulus for more tension.--Basing on this model behavior therapeutical techniques for breaking up this vicious circle are discussed.


Formulation, Optimization and In vitro / In vivo Characterization of Spray Dried Doxorubicin Loaded Folic Acid Conjugated Gelatin Nanoparticles.
Formulation, optimization and anticancer activity of spray-dried Doxorubicin loaded folic acid conjugated Gelatin nanoparticles (DOX-FA-GN). Doxorubicin loaded gelatin nanoparticles (DOX-GN) were prepared by the Coacervation phase separation method, optimized using DoE and then conjugated with folic acid by covalent coupling to formulate Doxorubicin loaded folic acid conjugated nanoparticles (DOX-FA-GN). The formulated nanoparticles were characterized to evaluate its physicochemical properties. Cellular uptake and cell viability studies were carried out using MTT assay and biodistribution studies were carried out in Wistar rats. Particle size, PDI and entrapment efficiency for optimized DOX-GN were found to be 152.3 ± 9.3 nm 0.294 ± 0.1 and 86.9± 3.4% while for DOX-FA-GN, 193.9 ± 12.3 nm 0.247 ± 0.2 and 84 ± 3.6%. The cytotoxic studies showed a cell viability of 75.1% for DOX-GN and 29.5% DOX-FA-GN. Biodistribution studies were found to be statistically insignificant for conjugated nanoparticles with excellent flow properties. Significantly higher DOX distribution in the lungs was observed in the case of DOX-FA-GN. There was a higher uptake of DOX on HeLa cells with DOX-FA-GN compared to DOX-GN. Also, the biodistribution of Dox in the lungs of Wistar rats was higher in conjugated nanoparticles as compared to unconjugated nanoparticles.


The impact of social cognition training on recovery from psychosis.
Social cognition training is an emerging intervention, which aims to ameliorate impairment in social interaction and improve functional outcomes in persons with a psychosis. This article reviews the research conducted on the impact of this intervention published in English language journals over the past 2 years. Social cognition training comprises three types of programs; targeted, broad-based, and comprehensive - targeted programs being the most effective. Programs largely focus on the domains of facial affect, or emotion recognition (FAR), Theory of Mind (ToM), and attributional bias. There is some evidence that ToM is amenable to change, but not FAR and attributional bias. Interventions designed to ameliorate impairment in social functioning largely involve a skills training laboratory model underpinned by social learning theory. The evidence for the effectiveness of current social cognition training strategies to improve functional outcome for persons with psychosis in general and schizophrenia in particular remains equivocal. Clearly, further work is required beyond the laboratory training model and future research may well benefit from the inclusion of longitudinal naturalistic studies.


Reversible Modulation of the Electronic and Spatial Environment around Ni(0) Centers Bearing Multifunctional Carbene Ligands with Triarylaluminum.
Designing and modulating the electronic and spatial environments surrounding metal centers is a crucial issue in a wide range of chemistry fields that use organometallic compounds. Herein, we demonstrate a Lewis-acid-mediated reversible expansion, contraction, and transformation of the spatial environment surrounding nickel(0) centers that bear N-phosphine oxide-substituted N-heterocyclic carbenes (henceforth referred to as (S)PoxIms). Reaction between tetrahedral (syn-κ-C,O-(S)PoxIm)Ni(CO)2 and Al(C6F5)3 smoothly afforded heterobimetallic Ni/Al species such as trigonal-planar {κ-C-Ni(CO)2}(μ-anti-(S)PoxIm){κ-O-Al(C6F5)3} via a complexation-induced rotation of the N-phosphine oxide moieties, while the addition of 4-dimethylaminopyridine resulted in the quantitative regeneration of the former Ni complexes. The corresponding interconversion also occurred between (SPoxIm)Ni(η2:η2-diphenyldivinylsilane) and {κ-C-Ni(η2:η2-diene)}(μ-anti-SPoxIm){κ-O-Al(C6F5)3} via the coordination and dissociation of Al(C6F5)3. The shape and size of the space around the Ni(0) center was drastically changed through this Lewis-acid-mediated interconversion. Moreover, the multinuclear NMR, IR, and XAS analyses of the aforementioned carbonyl complexes clarified the details of the changes in the electronic states on the Ni centers; i.e., the electron delocalization was effectively enhanced among the Ni atom and CO ligands in the heterobimetallic Ni/Al species. The results presented in this work thus provide a strategy for reversibly modulating both the electronic and spatial environment of organometallic complexes, in addition to the well-accepted Lewis-base-mediated ligand-substitution methods.


Susceptibility of glutathione peroxidase and glutathione reductase to oxidative damage and the protective effect of spin trapping agents.
Susceptibility of two key protective enzymes, glutathione peroxidase (GPX) and glutathione reductase (GR), to oxidative damage and the possible protective action of spin traps have been studied. Several oxidizing protocols including: (a) Fe(II) or Fe(III)/ascorbate, (b) a singlet oxygen producing system (methylene blue and visible light), (c) ozone, and (d) a hydroxyl radical-generating system (hydrogen peroxide/uv light) have been employed. Our results show that both enzymes are susceptible to oxidative modification and damage as indicated by the loss of activity and formation of carbonyl groups (in the case of GR). Treatment of GR with any of the mentioned oxidants resulted in formation of carbonyl groups and inactivation except when treated with iron, where the observed carbonyl formation was not accompanied with significant activity loss. GPX was inactivated to varying degrees when treated with the mentioned oxidants, but no carbonyls were detected. Ultraviolet exposure per se resulted in inactivation of both enzymes. Presence of the spin traps N-tert-butyl-alpha-phenylnitrone or 5,5'-dimethyl-1-pyroline-N-oxide was effective in protecting the enzymes against oxidation by uv, hydrogen peroxide/uv, and ozone as determined by the preservation of activity and decreased carbonyl content. The degree of protection, however, was found to be specific for each enzyme and for the employed oxidizing system.


Combination chemotherapy for advanced diffuse large cell lymphoma. The adverse effects of bone marrow invasion, gastrointestinal tract involvement or high bulk disease.
Thirty-nine adults with clinical stage III or IV diffuse large cell lymphoma were prospectively randomised to receive etoposide with doxorubicin (Group 1: n = 17), the same schedule of etoposide with carminomycin (Group 2: n = 8), or BACOP (Group 3: n = 14). The complete remission rates were respectively 24%, 25% and 28%, and further good partial remissions were 41%, 25% and 14%. The incidence of adverse prognostic factors was examined with the first two groups combined for comparison to patients receiving BACOP. The low complete remission rates were attributable to bone marrow invasion in 64% (16/25) of patients in groups 1 and 2, and 64% (9/14) in group 3; to extensive gastrointestinal tract involvement in 24% (6/25) of patients in groups 1 and 2, and 36% (5/14) in group 3; and to high bulk disease in 24% (6/25) of patients in groups 1 and 2, and 36% (5/14) in group 3. Actuarially predicted survival has not been reached for group 1, is 12 months for group 2, and 8 months for group 3; these different trends are not statistically significant. The trial was discontinued when it became clear that there was no difference between the two- and five-drug treatment regimens and that unacceptably low remission rates were obtained in patients having a high incidence of these poor prognostic factors, particularly when compared with results being reported in regimens that contain high or intermediate doses of methotrexate.


Effect of a Semisolid Formulation of Linum usitatissimum L. (Linseed) Oil on the Repair of Skin Wounds.
The purpose of this study was to investigate the effects of a semisolid formulation of linseed oil, SSFLO (1%, 5%, or 10%) or in natura linseed oil on skin wounds of rats. We used wound models, incisional and excisional, to evaluate, respectively, the contraction/reepithelialization of the wound and resistance to mechanical traction. The groups (n = 6) treated with SSFLO (1% or 5%) began the process of reepithelialization, to a significant extent (P < .05), on the sixth day, when compared to the petroleum jelly control group. On 14th day for the groups treated with SSFLO (1% or 5%), 100% reepithelialization was found, while in the petroleum jelly control group, this was only 33.33%. Our study showed that topical administration of SSFLO (1% or 5%) in excisional wounds allowed reepithelialization in 100% of treated animals. Therefore, a therapeutic potential of linseed oil, when used at low concentrations in the solid pharmaceutical formulations, is suggested for the process of dermal repair.


A reassessment of explanations for discordant introgressions of mitochondrial and nuclear genomes.
Hybridization is increasingly recognized as a significant evolutionary process, in particular because it can lead to introgression of genes from one species to another. A striking pattern of discordance in the amount of introgression between mitochondrial and nuclear markers exists such that substantial mitochondrial introgression is often found in combination with no or little nuclear introgression. Multiple mechanisms have been proposed to explain this discordance, including positive selection for introgressing mitochondrial variants, several types of sex-biases, drift, negative selection against introgression in the nuclear genome, and spatial expansion. Most of these hypotheses are verbal, and have not been quantitatively evaluated so far. We use individual-based, multilocus, computer simulations of secondary contact under a wide range of demographic and genetic scenarios to evaluate the ability of the different mechanisms to produce discordant introgression. Sex-biases and spatial expansions fail to produce substantial mito-nuclear discordance. Drift and nuclear selection can produce strong discordance, but only under a limited range of conditions. In contrast, selection on the mitochondrial genome produces strong discordance, particularly when dispersal rates are low. However, commonly used statistical tests have little power to detect this selection. Altogether, these results dismiss several popular hypotheses, and provide support for adaptive mitochondrial introgression.


Validation of the Crohn's and Ulcerative Colitis questionnaire in patients with acute severe ulcerative colitis.
The Crohn's and Ulcerative Colitis questionnaire (CUCQ) has previously been validated in patients with mild to moderate Crohn's and ulcerative colitis (UC). The aim of this study was to validate the tool in patients with acute severe UC. We undertook a validation of the CUCQ in patients recruited to the COmparison of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis Trial (CONSTRUCT). We carried out psychometric analysis to examine the underlying dimensions of the scale, internal consistency and construct validity. We carried out stepwise regression to examine which items accounted for the greatest variance in the scale. We obtained complete data for 270 patients. The internal consistency of the CUCQ was excellent (Cronbach's alpha > 0.8). The CUCQ scores achieved significant correlations with two generic quality of life scales (SF-12 and EQ-5D), demonstrating good construct validity. Stepwise regression identified 16 items that accounted for greater than 95% of the variance of the CUCQ. Only three of the eight items selected for a short form in mild to moderate patients were selected for patients with acute severe UC. The CUCQ demonstrated good validity in our sample of acute severe UC patients. Stepwise regression identified potential to shorten the tool, but that different items would be selected compared with less severe patients. If the tool is to be applied across the spectrum of disease it would be more appropriate to use the full 32 items in the scale. Further work to explore test-retest is required in acute patients.


Real-world opioid use among patients with migraine enrolled in US commercial insurance and risk factors associated with migraine progression.
BACKGROUND: Migraineurs may be categorized as having episodic migraine (EM: < 15 headache days/month) or chronic migraine (CM: ≥ 15 days/month for > 3 months with ≥ 8 days/month having features of migraine). Opioid use has been linked to progression from EM to CM. OBJECTIVE: To describe the utilization of opioid prescriptions among patients with migraine, to determine the association between opioid use and migraine progression, and to explore demographic and clinical risk factors for migraine progression. METHODS: This retrospective cohort study used Optum's deidentified Clinformatics Data Mart Database from January 2015 to December 2018. Adult patients with a migraine diagnosis and continuous health plan enrollment were included. Opioid use was measured by average daily morphine equivalent dose, also known as morphine milligram equivalent (MME). Descriptive statistics were used to summarize the opioid use by patient demographic and clinical characteristics. A Cox proportional hazards model with stepwise selection was used to determine the risk factors of new-onset CM. RESULTS: Overall, 35% of patients with migraine (27,331 of 78,134) received prescription opioids (> 0 MME/day) during the 12-month follow-up period. Higher opioid dosage was found in patients who had CM and comorbidities of interest. Compared with patients with EM, patients with CM were twice as likely to receive at least 20 MME/day (CM 3.8% vs EM 1.9%) and had a higher median opioid day supply (CM 20 vs EM 10) during follow-up. About 7% of patients with CM with at least 1 opioid prescription had at least 50 MME/day in any 90-day period during follow-up. A significant association was found between MME level and the likelihood of new-onset CM. Additional significant risk factors of migraine progression included younger age, female sex, South and West regions, and having a diagnosis of medication overuse headache, depression, back pain, or fibromyalgia (all P < 0.05). CONCLUSIONS: Despite guidelines and the availability of more migraine-specific treatments, opioids are still commonly prescribed to patients with migraines in real-world practice, especially for those with CM. In this study population, a higher risk of new-onset CM was associated with receiving higher opioid doses.


Pericardioesophageal fistula following left atrial ablation procedure.
We present a case of pericardioesophageal fistula formation in a 40 year old male who 23 days after undergoing a repeat ablation procedure for atrial fibrillation developed chest pressure, chills and diaphoresis. After initial labs and tests that demonstrated no evidence for acute myocardial ischemia, the patient underwent CT angiography of the chest. The study revealed pneumopericardium and a pericardial effusion. Suspicion was raised of perforation of the posterior left atrial myocardial wall with injury to adjacent esophagus. Water soluble contrast with transition to barium sulfate esophagram subsequently performed identified a perforation further affirming the postulate of a fistulous communication between the esophagus and pericardium. Transthoracic echocardiogram confirmed pericardial effusion but did not demonstrate myocardial defect. Endoscopic management was preferred and an esophageal stent was placed. Follow up esophagram showed an intact esophageal stent without evidence of extravasation.


Protein kinase A- and C-dependent modulation of murine inducible nitric oxide synthase.
Effects of pharmacological modulation of protein kinase A, C and G (PKA, PKC and PKG) were examined on inducible form of nitric oxide synthase (iNOS) expressed in COS cells to elucidate regulatory mechanism of iNOS by protein kinases. Formation of nitric oxide (NO), as an index of NOS activity, was assessed by measurement of nitrite in incubation medium in long term observation and by hemoglobin assay method in kinetic study. In long term observation (18 hours), activation of PKA by 8-Br-cAMP increased NO formation that was inhibited by N-(2-[p-bromocinnamylamino] ethyl)-5-isoquinolinesulfonamide (H89). Though activation of PKC by 12-O-tetradecanoyl phorbol-13-acetate (TPA) decreased NO formation, PKC inhibitor, chelerythrine, failed to inhibit the decrease. Activation of PKG with 8-Br-cGMP and inhibition with KT5823 resulted in no change in NO formation. Western blot analysis revealed that neither 8-Br-cAMP nor TPA affect iNOS expression. In kinetic study (short term perfusion study), no change in NO formation was observed by 8-Br-cAMP and TPA. These results indicate that, in living cells, PKG does not play a regulatory role in iNOS activity and that PKA and PKC do not directly modulate iNOS activity. However, PKA and PKC would possibly modify NOS activity indirectly via cofactors necessary for NO formation.


Power scalers: the new boom in contemporary periodontics.
The choice of which type of instrumentation to use remains the decision of the practitioner. It all depends on what goal the clinician hopes to achieve, the resources, and the physical set up within which they work. While speed in debridement, coupled with ease of use and comfort to the patient and practitioner are all important, the primary goal must always remain the optimal healing and success of the dental procedure. With improved tip designs and efficiency, power scaling has the ability to improve dental hygiene and periodontal care in the future.


Localization of Porphyromonas gingivalis-carrying fimbriae in situ in human periodontal pockets.
Fimbriae, which are involved in adherence, constitute an important pathogenic factor of Porphyromonas gingivalis. In vivo, however, the distribution of P. gingivalis-carrying fimbriae is unknown. The localization of P. gingivalis-carrying fimbriae was examined in situ. From 19 patients with severe periodontitis and P. gingivalis, we obtained 20 teeth with periodontal tissue attached, with and without immunolocalized fimbriae. Eleven teeth were subjected to light microscopy, 9 to electron microscopy. In 6 of the 11 samples examined, we detected positive reactions with an anti-P. gingivalis-fimbriae serum, located in the cementum-attached plaque area in the deep pocket zones. In the so-called 'plaque-free zones', P. gingivalis-carrying fimbriae were immunocytochemically observed to reside in contact with the dental cuticle in 6 of the 9 samples examined. These findings suggest that P. gingivalis-carrying fimbriae are strongly related to adherence to the root surface at the bottoms of human periodontal pockets.


DNA and histones impair the mechanical stability and lytic susceptibility of fibrin formed by staphylocoagulase.
Staphylocoagulase (SCG) is a virulence factor of Staphylococcus aureus, one of the most lethal pathogens of our times. The complex of SCG with prothrombin (SCG/ProT) can clot fibrinogen, and SCG/ProT-induced fibrin and plasma clots have been described to show decreased mechanical and lytic resistance, which may contribute to septic emboli from infected cardiac vegetations. At infection sites, neutrophils can release DNA and histones, as parts of neutrophil extracellular traps (NETs), which in turn favor thrombosis, inhibit fibrinolysis and strengthen clot structure. To characterize the combined effects of major NET-components (DNA, histone H1 and H3) on SCG/ProT-induced clot structure, mechanical and lytic stability. Recombinant SCG was used to clot purified fibrinogen and plasma. The kinetics of formation and lysis of fibrin and plasma clots containing H1 or core histones+/-DNA were followed by turbidimetry. Fibrin structure and mechanical stability were characterized with scanning electron microscopy, pressure-driven permeation, and oscillation rheometry. Histones and DNA favored the formation of thicker fibrin fibers and a more heterogeneous clot structure including high porosity with H1 histone, whereas low porosity with core histones and DNA. As opposed to previous observations with thrombin-induced clots, SCG/ProT-induced fibrin was not mechanically stabilized by histones. Similarly to thrombin-induced clots, the DNA-histone complexes prolonged fibrinolysis with tissue-type plasminogen activator (up to 2-fold). The anti-fibrinolytic effect of the DNA and DNA-H3 complex was observed in plasma clots too. Heparin (low molecular weight) accelerated the lysis of SCG/ProT-clots from plasma, even if DNA and histones were also present. In the interplay of NETs and fibrin formed by SCG, DNA and histones promote structural heterogeneity in the clots, and fail to stabilize them against mechanical stress. The DNA-histone complexes render the SCG-fibrin more resistant to lysis and thereby less prone to embolization.


Personality characteristics in juvenile tension headache and migraine.
The authors report the personality characteristics of 30 subjects, 16 males and 14 females, average age 13.7 years: 13 suffered from migraine without aura, 8 from migraine with aura and 9 from chronic tension-type headache. The study was based on a detailed clinical assessment (psychodynamically-oriented interviews with the child and its parents) and evaluation by tests. A blind test of the clinical personality characteristics was then carried out. The results of these investigations indicated that 13/30 of the subjects had a neurotic personality organization, 12/30 were borderline and 5/30 had a "white relation". Given the subjects' youth, these conditions are probably to be considered transient. From the data collected it seems that migrainous subjects are distributed along a continuum that ranges from one end characterized by more evolved and adaptive mental organization and defence mechanisms and the opposite end, where mental organization is less evolved and adaptive and at a greater risk of somatization.


The use of art and music therapy in substance abuse treatment programs.
Although the implementation of evidence-based practices in the treatment of substance use disorders has attracted substantial research attention, little consideration has been given to parallel implementation of complementary and alternative medical (CAM) practices. Using data from a nationally representative sample (N = 299) of U.S. substance abuse treatment programs, this study modeled organizational factors falling in the domains of patient characteristics, treatment ideologies, and structural characteristics, associated with the use of art therapy and music therapy. We found that 36.8% of treatment programs offered art therapy and 14.7% of programs offered music therapy. Programs with a greater proportion of women were more likely to use both therapies, and programs with larger proportions of adolescents were more likely to offer music therapy. In terms of other treatment ideologies, programs' use of Motivational Enhancement Therapy was positively related to offering art therapy, whereas use of contingency management was positively associated with offering music therapy. Finally, our findings showed a significant relationship between requiring 12-step meetings and the use of both art therapy and music therapy. With increasing use of CAM in a diverse range of medical settings and recent federal legislation likely to reduce barriers in accessing CAM, the inclusion of CAM in addiction treatment is growing in importance. Our findings suggest treatment programs may be utilizing art and music therapies to address unique patient needs of women and adolescents.


Photoinduced processes in nucleic acids and proteins: concluding remarks.
Light induced charge and energy transport in nucleic acids and proteins is the basis of fundamental biological processes such as photosynthesis, vision, DNA-photostability, DNA-photodamage and photosensing. This article summarises the concluding remarks given at the Faraday Discussions meeting on this topic. The specific themes arising from the meeting that are discussed herein include charge transfer in nucleic acids and proteins, excited state dynamics and topology, vibrations and dynamic disorder, proteins and charge transfer states, nanobiophotonics coupled to biomedical applications and photosynthesis.


Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) of cadaveric shoulders: comparison of contrast dynamics in hyaline and fibrous cartilage after intraarticular gadolinium injection.
Delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) is a novel method to investigate cartilaginous and fibrocartilaginous structures. To investigate the contrast dynamics in hyaline and fibrous cartilage of the glenohumeral joint after intraarticular injection of gadopentetate dimeglumine. Transverse T(1) maps were acquired on a 1.5T scanner before and after intraarticular injection of 2.0 mmol/l gadopentetate dimeglumine in five cadaveric shoulders using a dual flip angle three-dimensional gradient echo (3D-GRE) sequence. The acquisition time for the T(1) maps was 5 min 5 s for the whole shoulder. Measurements were repeated every 15 min over 2.5 hours. Regions of interest (ROIs) covering the glenoid cartilage and the labrum were drawn to assess the temporal evolution of the relaxation parameters. T(1) of unenhanced hyaline cartilage of the glenoid was 568+/-34 ms. T(1) of unenhanced fibrous cartilage of the labrum was 552+/-38 ms. Significant differences (P=0.002 and 0.03) in the relaxation parameters were already measurable after 15 min. After 2 to 2.5 hours, hyaline and fibrous cartilage still demonstrated decreasing relaxation parameters, with a larger range of the T(1)(Gd) values in fibrous cartilage. T(1) and triangle Delta R(1) values of hyaline and fibrous cartilage after 2.5 hours were 351+/-16 ms and 1.1+/-0.09 s(-1), and 332+/-31 ms and 1.2+/-0.1 s(-1), respectively. A significant decrease in T(1)(Gd) was found 15 min after intraarticular contrast injection. Contrast accumulation was faster in hyaline than in fibrous cartilage. After 2.5 hours, contrast accumulation showed a higher rate of decrease in hyaline cartilage, but neither hyaline nor fibrous cartilage had reached equilibrium.


[Method for analyzing and estimating human resources for maternal and child care programs].
This report described the version of the Human Resources Analysis and Estimation Method (MAERH) that was specially devised for analyzing maternal and child health and family planning personnel (the MAERH/AMI/1 version). The general features of the method are presented and its ability to analyze health programs and to estimate the human resources needed is emphasized. In addition, the operation and use of the method, its advantages and short-comings, as well as its development and possible adaptation to wider-ranging or more specific problems are described. Finally, the results obtained in the maternal and child health area of the State of Pernambuco, Brazil, are presented to exemplify the use of the method.


A Cytochrome P450-Mediated Intramolecular Carbon-Carbon Ring Closure in the Biosynthesis of Multidrug-Resistance-Reversing Lathyrane Diterpenoids.
The Euphorbiaceae produce a wide variety of bioactive diterpenoids. These include the lathyranes, which have received much interest due to their ability to inhibit the ABC transporters responsible for the loss of efficacy of many chemotherapy drugs. The lathyranes are also intermediates in the biosynthesis of range of other bioactive diterpenoids with potential applications in the treatment of pain, HIV and cancer. We report here a gene cluster from Jatropha curcas that contains the genes required to convert geranylgeranyl pyrophosphate into a number of diterpenoids, including the lathyranes jolkinol C and epi-jolkinol C. The conversion of casbene to the lathyranes involves an intramolecular carbon-carbon ring closure. This requires the activity of two cytochrome P450s that we propose form a 6-hydroxy-5,9-diketocasbene intermediate, which then undergoes an aldol reaction. The discovery of the P450 genes required to convert casbene to lathyranes will allow the scalable heterologous production of these potential anticancer drugs, which can often only be sourced in limited quantities from their native plant.


Suboptimal Prenatal Syphilis Testing Among Commercially Insured Women in the United States, 2013.
United States surveillance data demonstrate that congenital syphilis cases are increasing. We performed an analysis of commercially insured pregnant females using MarketSan to determine syphilis screening rates at different prenatal stages; 85% of pregnant women in this population had a syphilis test performed at least once during the prenatal period.


Anatomical evidence for direct connections between the shell and core subregions of the rat nucleus accumbens.
The nucleus accumbens is thought to subserve different aspects of adaptive and emotional behaviors. The anatomical substrates for such actions are multiple, parallel ventral striatopallidal output circuits originating in the nucleus accumbens shell and core subregions. Several indirect ways of interaction between the two subregions and their associated circuitry have been proposed, in particular through striato-pallido-thalamic and dopaminergic pathways. In this study, using anterograde neuroanatomical tracing with Phaseolus vulgaris-leucoagglutinin and biotinylated dextran amine as well as single-cell juxtacellular filling with neurobiotin, we investigated the intra-accumbens distribution of local axon collaterals for the identification of possible direct connections between the shell and core subregions. Our results show widespread intra-accumbens projection patterns, including reciprocal projections between specific parts of the shell and core. However, fibers originating in the core reach more distant areas of the shell, including the rostral pole (i.e. the calbindin-poor part of the shell anterior to the core) and striatal parts of the olfactory tubercle, than those arising in the shell and projecting to the core. The latter projections are more restricted to the border region between the shell and core. The density of the fiber labeling within both the shell and core was very similar. Moreover, specific intrinsic projections within shell and core were identified, including a relatively strong projection from the rostral pole to the rostral shell, reciprocal projections between the rostral and caudal shell, as well as projections within the core that have a caudal-to-rostral predominance. The results of the juxtacellular filling experiments show that medium-sized spiny projection neurons and medium-sized aspiny neurons (most likely fast-spiking) contribute to these intra-accumbens projections. While such neurons are GABAergic, the intrastriatal projection patterns indicate the existence of lateral inhibitory interactions within, as well as between, shell and core subregions of the nucleus accumbens.


Live animals for preclinical medical student surgical training.
The use of live animals for surgical training is a well-known, deliberated topic. However, medical students who use live animals rate the experience high not only in improving their surgical techniques, but also positively influencing their confidence levels in the operating room later in their careers. Therefore, we hypothesized that the use of live animal models is a unique and influential component of preclinical medical education. Medical student performed the following surgical procedures using mice; surgical orthotopic implantation of cancer cells into fat pad and subsequently a radical mastectomy. The improvement of skill was then analyzed. All cancer cell inoculations were performed successfully. Improvement of surgical skills during the radical mastectomy procedure was documented in all parameters. All wounds healed without breakdown or dehiscence. The appropriate interval between interrupted sutures was ascertained after fifth wound closure. The speed of interrupted sutures was doubled by last wound closure. The time required to complete a radical mastectomy decreased by almost half. A single animal died immediately following the operation due to inappropriate anesthesia, which was attributed to the lack of understanding of the overall operative management. Surgical training using live animals for preclinical medical students provides a unique learning experience, not only in improving surgical skills but also and arguably most importantly, to introduce the student to the complexities of the perioperative environment in a way that most closely resembles the stress and responsibility that the operating room demands.


Specific facial signals associate with categories of social actions conveyed through questions.
The early recognition of fundamental social actions, like questions, is crucial for understanding the speaker's intended message and planning a timely response in conversation. Questions themselves may express more than one social action category (e.g., an information request "What time is it?", an invitation "Will you come to my party?" or a criticism "Are you crazy?"). Although human language use occurs predominantly in a multimodal context, prior research on social actions has mainly focused on the verbal modality. This study breaks new ground by investigating how conversational facial signals may map onto the expression of different types of social actions conveyed through questions. The distribution, timing, and temporal organization of facial signals across social actions was analysed in a rich corpus of naturalistic, dyadic face-to-face Dutch conversations. These social actions were: Information Requests, Understanding Checks, Self-Directed questions, Stance or Sentiment questions, Other-Initiated Repairs, Active Participation questions, questions for Structuring, Initiating or Maintaining Conversation, and Plans and Actions questions. This is the first study to reveal differences in distribution and timing of facial signals across different types of social actions. The findings raise the possibility that facial signals may facilitate social action recognition during language processing in multimodal face-to-face interaction.


Clinical isolation and characterization of Yersinia enterocolitica in China using real-time PCR and culture method.
To carry out a preliminary epidemiological investigation of Yersinia enterocolitica from a clinical perspective in China and to further validate the consistency of real-time polymerase chain reaction (RT-PCR) and culture method. 700 stool samples were randomly and continuously collected from in- and outpatients with diarrhea, which were detected by both the culture method and RT-PCR. All 52 positive samples were successfully detected by both RT-PCR and the culture method. The total incidence of yersiniosis was about 7.4%, which was statistically higher than before (0.65%) by the Mann-Whitney U test. The morbidity was not significant between males and females (U = 0.354, p > 0.05) by the Mann-Whitney U test whereas it was significant between children and adults (U = 2.06, p < 0.05) as well as between the autumn-winter and spring-summer (U = 2.04, p < 0.05) months. Moreover, the constituent ratio of children and adults with yersiniosis in different systems was not significant by the McNemer test while it was significant between children and adults in the incidence of extraintestinal infection (U = 2.51, p < 0.05). RT-PCR with better applicability will become an efficient tool for detection of virulent Y. enterocolitica and will also be used as an alternative to the culture method. Due to the higher incidence than before, we should publicize dietary hygiene and pay more attention to earlier diagnosis for yersiniosis and its complications, aiming at children <4 years and adults >60 years during the autumn-winter months.


Overgrowth.
Overgrowth presenting at birth requires blood glucose monitoring while a cause is sought. Among older children presenting with tall stature, common causes such as familial tall stature and simple obesity must be distinguished from rarer endocrine and genetic causes. Several genetic overgrowth syndromes carry increased risk of malignancy and regular screening is recommended. The use of high-dose oestrogen or testosterone in an attempt to limit final stature has limited efficacy and carries a significant risk of side effects. Endocrine and genetic assessment ought to be considered for cases of unexplained overgrowth.


Alkaloids from the leaves of Uncaria rhynchophylla and their inhibitory activity on NO production in lipopolysaccharide-activated microglia.
Two new isomeric alkaloids, 18,19-dehydrocorynoxinic acid B (1) and 18,19-dehydrocorynoxinic acid (2), were isolated from the CHCl3 extract of the leaves of Uncaria rhynchophylla, together with four known rhynchophylline-type alkaloids, corynoxeine (3), isocorynoxeine (4), rhynchophylline (5), and isorhynchophylline (6), and an indole alkaloid glucoside, vincoside lactam (7). The structures of compounds 1 and 2 were elucidated by spectroscopic methods including UV, IR, HREIMS, 1D and 2D NMR, and CD experiments. The activity assay showed that compounds 3-6, with a C-16 carboxylic ester group, and 7 exhibited inhibitory activity on lipopolysaccharide (LPS)-induced NO release in primary cultured rat cortical microglia (IC 50: 13.7-19.0 microM). However, only weak inhibitory activity was observed for compounds 1 and 2, with a C-16 carboxylic acid group (IC 50: >100 microM).


Photoisomerization of β-Ionone Protonated Schiff Base in the Gas Phase.
The photoisomerization of β-ionone protonated Schiff base (BIPSB) is investigated in the gas phase by irradiating mobility-selected ions in a tandem ion mobility spectrometer with tunable radiation. Four distinguishable isomers are produced by electrospray ionization whose structures are deduced from their collision cross sections and photoisomerization behavior along with density functional theory calculations. They include two geometric isomers of BIPSB with trans or cis configurations about the polyene chain's terminal C═N double bond, a bicyclic structure formed through electrocyclization of the polyene chain, and a Z-retro-γ-ionone isomer. Although trans-BIPSB and 9-cis-BIPSB have similar photoisomerization action spectra, with a maximum response at 375 nm, they photoconvert to different isomers. The trans-BIPSB isomer transforms to the bicyclic form upon exposure to light over the 320-400 nm range, whereas the cis-BIPSB isomer is prevented by steric hindrance from forming the bicyclic BIPSB isomer following irradiation and is proposed instead to form the 7,9-di-cis isomer. Neither the bicyclic isomer nor the Z-retro-γ-ionone isomer respond strongly to near-UV light.


Baikalobia elochinensis sp. n. (Plathelminthes, Tricladida, Continenticola), a new species of endemic Baikal planarians: morphological and genetic comparison with the type species Baikalobia guttata (Gerstfeldt, 1858).
Endemic freshwater planarians of the family Dendrocoelidae (Plathelminthes, Tricladida, Continenticola) are characteristic components of the Baikal fauna. Despite the long history of research on this group, new species and genera of Baikal planarians have been regularly described (Porfirieva, 1977; Timoshkin et al., 2004; Porfiriev et al., 2009; Porfiriev et al., 2011; Porfiriev and Timoshkin, 2013; Porfiriev and Timoshkin, 2015).


The missing link: bridging the patient-provider health information gap.
Widespread adoption of information technology is now regarded as a pathway to improving health care and achieving the Institute of Medicine's highly regarded six aims for redesigning care. Achieving these aims requires fresh approaches to health system design, including continuous healing relationships between physicians and patients and provision of tools to help patients be more active participants in their own care. Personal health records (PHRs) might allow patients and providers to develop new ways of collaborating and provide the basis for broader transformation of the health care system. Federal policies can be key catalysts in accelerating PHR development and adoption.


[Establishment of an educational program concerning adverse drug reaction reporting-system in long-term practical training at a hospital].
The model core curriculum for pharmaceutical education specifies the specific behavioral objectives (SBOs) concerning adverse drug reactions, which aims to train pharmacy students to manage adverse drug reactions. Fukuoka University Hospital has developed a problem-based learning (PBL) program concerning adverse drug reactions as long-term practical training to collect adverse event information, identify adverse effects, and acquire management skills. Students' level of satisfaction with the program was high (approximately 90%), and the mean self-evaluation score for the SBOs concerning adverse reaction was 4.4 (5-grade scale), showing a high level of understanding. In addition, students' will of participation to the adverse drug reaction-reporting system was significantly improved after the PBL program, showing the usefulness of this program (p=0.02). However, the results of the PBL program revealed students' insufficient knowledge of adverse reactions and lack of reviewing skills, suggesting the need to improve the education system whereby students can learn adverse drug reactions in clinical settings.


Acute suppurative thyroiditis in a primary intrathoracic goiter.
To describe a case of acute suppurative thyroiditis and focal abscess formation in a patient with a primary intrathoracic goiter. We summarize the initial clinical manifestations, the pathologic findings, and the surgical treatment of a woman with an enlarging mediastinal mass. A 41-year-old woman had a fever and a sudden increase in severity of compressive symptoms after a remote urinary tract infection. Smears from an intraoperative fine-needle aspiration biopsy showed necrotic debris, polymorphonuclear leukocytes, hemosiderin-laden macrophages, and degenerated follicular epithelial cells. Urine and tissue cultures grew Escherichia coli. The patient underwent resection of an 800-g primary intrathoracic goiter with associated degeneration, necrosis, hemorrhage, and abscess formation. To our knowledge, this is the first reported case of acute suppurative thyroiditis and abscess formation occurring within a primary intrathoracic goiter.


The Steady-State ALTADENA RASER Generates Continuous NMR Signals.
The front cover artwork is provided by Dr. Lehmkuhl's group at the Karlsruhe Institute of Technology. The image shows continuous NMR signals complemented by a simulated bifurcation diagram of a nonlinear RASER system. Read the full text of the Research Article at 10.1002/cphc.202300204.


Control of the development and prevalence of antimicrobial resistance in bacteria of food animal origin in Japan: a new approach for risk management of antimicrobial veterinary medicinal products in Japan.
Antimicrobial agents are essential for controlling bacterial disease in food-producing animals and contribute to the stable production of safe animal products. The use of antimicrobial agents in these animals affects the emergence and prevalence of antimicrobial resistance in bacteria isolated from animals and animal products. As disease-causing bacteria are often transferred from food-producing animals to humans, the food chain is considered a route of transmission for the resistant bacteria and/or resistance genes. The Food Safety Commission of Japan (FSC) has been assessing the risk posed to human health by the transmission of antimicrobial-resistant bacteria from livestock products via the food chain. In addition to the FSC's risk assessments, the Japanese Ministry of Agriculture, Forestry and Fisheries has developed risk-management guidelines to determine feasible risk-management options for the use of antimicrobial veterinary medicinal products during farming practices. This report includes information on risk assessment and novel approaches for risk management of antimicrobial veterinary medicinal products for mitigating the risk of development and prevalence of antimicrobial resistance in bacteria originating from food-producing animals in Japan.


Prediction models for dementia and neuropathology in the oldest old: the Vantaa 85+ cohort study.
We developed multifactorial models for predicting incident dementia and brain pathology in the oldest old using the Vantaa 85+ cohort. We included participants without dementia at baseline and at least 2 years of follow-up (N = 245) for dementia prediction or with autopsy data (N = 163) for pathology. A supervised machine learning method was used for model development, considering sociodemographic, cognitive, clinical, vascular, and lifestyle factors, as well as APOE genotype. Neuropathological assessments included β-amyloid, neurofibrillary tangles and neuritic plaques, cerebral amyloid angiopathy (CAA), macro- and microscopic infarcts, α-synuclein pathology, hippocampal sclerosis, and TDP-43. Prediction model performance was evaluated using AUC for 10 × 10-fold cross-validation. Overall AUCs were 0.73 for dementia, 0.64-0.68 for Alzheimer's disease (AD)- or amyloid-related pathologies, 0.72 for macroinfarcts, and 0.61 for microinfarcts. Predictors for dementia were different from those in previous reports of younger populations; for example, age, sex, and vascular and lifestyle factors were not predictive. Predictors for dementia versus pathology were also different, because cognition and education predicted dementia but not AD- or amyloid-related pathologies. APOE genotype was most consistently present across all models. APOE alleles had a different impact: ε4 did not predict dementia, but it did predict all AD- or amyloid-related pathologies; ε2 predicted dementia, but it was protective against amyloid and neuropathological AD; and ε3ε3 was protective against dementia, neurofibrillary tangles, and CAA. Very few other factors were predictive of pathology. Differences between predictors for dementia in younger old versus oldest old populations, as well as for dementia versus pathology, should be considered more carefully in future studies.


Alternate muscle activity patterns among synergists of the quadriceps femoris including the vastus intermedius during low-level sustained contraction in men.
We quantified the alternate muscle activity among four synergists of the quadriceps femoris (QF), including the vastus intermedius (VI), during low-level sustained contraction. Surface electromyograms (EMGs) were recorded from the VI, vastus lateralis (VL), vastus medialis (VM), and rectus femoris (RF) in 11 healthy men during isometric knee extension at 2.5% maximum voluntary contraction for 60 min to determine alternate muscle activity among the four synergists of the QF. Alternate activity was primarily found between the RF and VI, VL, or VM, and rarely found among the vasti muscles. Multiple muscle comparison revealed the duration of alternate activity in the RF/VI+VL+VM combination remained high throughout the experiment, although the frequency of that combination did not. These results suggested that there is a fixed muscle combination, i.e., RF and the 3 vasti muscles, to perform low-intensity sustained contraction in the human QF.


An anatomical study of the junction of the orbital septum and the levator aponeurosis in Orientals.
The anatomical relationships of the orbital septum and levator aponeurosis has been studied in 40 eyelids subjected to blepharoplasty and corrective ptosis surgery by dissection in 10 cadavers and in histological sections. The orbital septum originates from the arcus marginalis of the frontal bone and consists of two layers. The whitish outer (superficial) layer, containing vertically running vessels, descends just inside the orbicularis oculi muscle to interdigitate with the levator aponeurosis with loose connective tissue, then disperses inferiorly. The inner (deep) layer follows the superficial one initially, then reflects at the levator aponeurosis and continues posteriorly with the levator sheath. We reconfirmed Whitnall's original description that the levator sheath thickens to form the superior transverse ligament runs continuously inferiorly anterior to the levator aponeurosis and forms the inner layer of the orbital septum. This detailed anatomical analysis should assist in performing upper eyelid surgery such as the Oriental double fold operation or levator resection.


The Mechanism Underlying the Influence of Indole-3-Propionic Acid: A Relevance to Metabolic Disorders.
The increasing prevalence of metabolic syndrome has become a serious public health problem. Certain bacteria-derived metabolites play a key role in maintaining human health by regulating the host metabolism. Recent evidence shows that indole-3-propionic acid content can be used to predict the occurrence and development of metabolic diseases. Supplementing indole-3-propionic acid can effectively improve metabolic disorders and is considered a promising metabolite. Therefore, this article systematically reviews the latest research on indole-3-propionic acid and elaborates its source of metabolism and its association with metabolic diseases. Indole-3-propionic acid can improve blood glucose and increase insulin sensitivity, inhibit liver lipid synthesis and inflammatory factors, correct intestinal microbial disorders, maintain the intestinal barrier, and suppress the intestinal immune response. The study of the mechanism of the metabolic benefits of indole-3-propionic acid is expected to be a potential compound for treating metabolic syndrome.


Induced dedifferentiation: a possible alternative to embryonic stem cell transplants.
Induction of local tissue regeneration in the human would best be accomplished if the patient's own cells at the desired site could be caused to dedifferentiate into the required embryonic stem cells. A system involving the electrical iontophoretic introduction of free silver ions into human wounds for their antibiotic effect has been in clinical use since 1975. In addition to a major antibiotic effect, the technique was found to produce the regeneration of all local tissues, apparently by stimulating dedifferentiation of mature human cells. More recently the use of a newly developed silvered nylon fabric has been found to have similar results without the need for electrical parameters. The results of a preliminary laboratory and clinical study of this material are presented.


Branhamella catarrhalis pneumonia and immunoglobulin abnormalities: a new association.
A case of Branhamella catarrhalis pneumonia in a patient with multiple myeloma is reported. With the inclusion of this case, 5 of 17 (29.4%) reported cases of Branhamella pneumonia or empyema have occurred in patients with underlying diseases associated with immunoglobulin abnormalities. This strong clinical association suggests that qualitatively and quantitatively normal immunoglobulins are important host defense mechanisms in preventing infection with this pathogen. The sputum Gram stain demonstrating kidney-shaped gram-negative diplococci may be an early clue to the diagnosis, as well as an initial guide to empiric therapy, and may help the laboratory isolate and identify this pathogen, which, because of its morphologic resemblance to Neisseria, is frequently reported as "normal flora".


Unmet Primary Care Needs in Diabetic Patients with Multimorbidity in a Medically Underserved Area.
Diabetic patients with multimorbidity in medically underserved minority communities are less engaged in primary care and experience high emergency department (ED) utilization. This study assesses unmet primary care needs among diabetic patients in a medically underserved area (MUA). A suburb of Memphis-Whitehaven, Tennessee (Shelby County, ZIP codes 38109 and 38116)-majority African American (96.6%) with 30.5% below the poverty level. Community case study using multiple data sources including diabetes registry, individual interviews, focus groups, and a survey of 30 ED patients with diabetes and multimorbidity. Diabetes registry data indicated that 95.5% of 5723 diabetic patients had multimorbidity. Over 91.5% were uncontrolled at some point in 2014 to 2015. Only 83% of patients with diabetes and multimorbidity reported having a primary care provider (PCP) and those without a PCP were more likely to report delays in needed care. Patients expressed strong interest in health coaching (88%) and receiving text messages from the doctor's office (73%). Individual patient interviews (n = 9) and focus groups (n = 11) revealed common primary care and self-care experiences and needs including diabetes education, improved patient-provider communication, health-care access and coverage, and strengthened primary care and community. This study demonstrates that almost 1 in 5 ED complex diabetic patients in an MUA do not have a PCP, and that difficulty accessing primary care often results in patients forgoing needed care. Qualitative findings support these conclusions. These results suggest that primary care capacity and infrastructure to support diabetes self-care need strengthening in MUAs.


[Fibrosing mediastinitis].
Up to date aspects of fibrosing mediastinitis are discussed in the review. The most common changes in the organs of mediastinum have been described with regard to surgical possibilities of their treatment, particularly superior caval vein syndrome, strictures of bronchial tree and pulmonary vessels and changes of the esophagus. The approach to rich literature has been pointed out.


Gardening Activities and Physical Health Among Older Adults: A Review of the Evidence.
Few studies have examined the health-related consequences of gardening among older adults. This scoping review summarizes and characterizes current research that examines the relationship between physical health and participation in planned gardening activities, including establishing, maintaining, or caring for plants. Six databases were searched. Eligible studies were published between 2000 and 2013, were published in English, and assessed different aspects of physical health (e.g., functional ability, energy expenditure, injury) for older adults who had participated in a planned gardening activity. Of the eight eligible studies identified with these criteria, four assessed energy expenditures and four assessed physical functioning. Studies assessing energy expenditures documented that the majority of gardening tasks were classified into low-to-moderate intensity physical activity. The current literature does not provide sufficient evidence of the physical functioning consequences of gardening. Future studies should consider how specific gardening interventions help older adults meet physical activity guidelines.


DANBIO--powerful research database and electronic patient record.
The nationwide DANBIO registry has been designed to capture operational clinical data as part of routine clinical care. At the same time, it provides a powerful research database. This article reviews the DANBIO registry with focus on problems and solutions of design, funding and linkage, provides an overview of the research outcome and presents the cohorts of RA patients. The registry, which is approved as a national quality registry, includes patients with RA, PsA and AS, who are followed longitudinally. Data are captured electronically from the source (patients and health personnel). The IT platform is based on open-source software. Via a unique personal identification code, linkage with various national registers is possible for research purposes. Since the year 2000, more than 10,000 patients have been included. The main focus of research has been on treatment efficacy and drug survival. Compared with RA patients, who were on conventional treatment with DMARDs, the patients who started biological treatment were younger, had longer disease duration, higher disease activity, tried more DMARDs and received more prednisolone. Also, more patients on biological therapy were seropositive and had erosive disease. However, the current levels of disease activities and the fraction of patients who had gone into remission in the two groups of patients were very similar. This indicates that clinicians have a common treatment goal for RA patients regardless of treatment. In conclusion, DANBIO serves as an electronic patient 'chronicle' in routine care, and at the same time provides a powerful research database.


Synthesis of In2O3 nanowire-decorated Ga2O3 nanobelt heterostructures and their electrical and field-emission properties.
We report on the synthesis of In2O3 nanowire-decorated Ga2O3 nanobelt heterostructures via a simple catalyst-free method. A typical heterostructure, where an In2O3 nanowire forms a sort of a "dorsal fin" on the Ga2O3 nanobelt, exhibits the T-shaped cross-section. The structure, electrical porperties, and field-emission properties of this material are systematically investigated. The heterostructures possess a typical n-type semiconducting behavior with enhanced conductivity. Field-emission measurements show that they have a low turn-on field (approximately 1.31 V/microm) and a high field-enhancement factor (over 4000). The excellent field-emission characteristics are attributed to their special geometry and good electrical properties. The present In2O3-decorated Ga2O3 heterostructures are envisaged to be decent field-emitters useful in advanced electronic and optoelectronic nanodevices.


Effect of omeprazole on ethanol oxidation and aniline hydroxylation in rat hepatic microsomes.
Omeprazole, a substituted benzimidazole, is a potent gastric acid antisecretory drug, which inhibits the hepatic oxidative drug metabolism in vitro and in vivo. The effect of omeprazole on the microsomal ethanol oxidizing system (MEOS) and, since ethanol-induced cytochrome P-450 reveals a high activity for aniline hydroxylation, on aniline hydroxylase (AH) has been investigated in rat liver microsomes. Omeprazole inhibits microsomal AH activity significantly in a dose dependent manner, while this was not the case for MEOS activity. These data give indirect evidence that the microsomal metabolism of both ethanol and aniline is mediated by different isoenzymes of cytochrome P-450 and that omeprazole exhibits a different affinity to both compounds. Therefore, it must be emphasized that drug interactions with omeprazole have to be tested experimentally in each individual case, since it is impossible to predict such interactions solely on the knowledge of the drug's metabolic pathway.