Developmental regulation of fear learning and anxiety behavior by endocannabinoids.
The developing brain undergoes substantial maturation into adulthood and the development of specific neural structures occurs on differing timelines. Transient imbalances between developmental trajectories of corticolimbic structures, which are known to contribute to regulation over fear learning and anxiety, can leave an individual susceptible to mental illness, particularly anxiety disorders. There is a substantial body of literature indicating that the endocannabinoid (eCB) system critically regulates stress responsivity and emotional behavior throughout the life span, making this system a novel therapeutic target for stress- and anxiety-related disorders. During early life and adolescence, corticolimbic eCB signaling changes dynamically and coincides with different sensitive periods of fear learning, suggesting that eCB signaling underlies age-specific fear learning responses. Moreover, perturbations to these normative fluctuations in corticolimbic eCB signaling, such as stress or cannabinoid exposure, could serve as a neural substrate contributing to alterations to the normative developmental trajectory of neural structures governing emotional behavior and fear learning. In this review, we first introduce the components of the eCB system and discuss clinical and rodent models showing eCB regulation of fear learning and anxiety in adulthood. Next, we highlight distinct fear learning and regulation profiles throughout development and discuss the ontogeny of the eCB system in the central nervous system, and models of pharmacological augmentation of eCB signaling during development in the context of fear learning and anxiety.


A randomized controlled trial for aggression and substance use involvement among Veterans: Impact of combining Motivational Interviewing, Cognitive Behavioral Treatment and telephone-based Continuing Care.
Physical aggression (towards partners or non-partners) is common among patients in treatment for substance use disorders (SUDs), including among Veteran samples; however, few treatment programs provide adjunct intervention approaches targeting reduction or prevention of aggression. The primary objectives of this comparative efficacy study were to examine the impact of adjunct aggression interventions delivered during treatment on aggression and substance use outcomes, including: a) an acute treatment phase 6-session integrated Motivational Interviewing-Cognitive Behavioral Treatment intervention (MI-CBT) for aggression and substance use prevention, b) MI-CBT plus a 12-week telephone-based Continuing Care (MI-CBT + CC) intervention, and c) an acute phase single session control condition [including some discussion of violence prevention and local violence prevention resources (Enhanced Treatment as Usual (E-TAU))]. Participants (N = 180; 165 males and 15 females) were Veterans with SUD problems and past-year severe aggression who were randomized to one of three conditions: MI-CBT, MI-CBT + CC, or E-TAU. Primary 12-month outcomes included physical aggression and injury to partners, non-partners, and total aggression (collapsing across partner and non-partner relationships). Substance use outcomes included heavy drinking, marijuana use, cocaine use, and overall illicit substance use. Due to low representation in the sample (n = 4 women in each group at follow-up), women were excluded from primary analyses. According to unadjusted analyses of male participants, all groups showed similar significant declines in aggression over time, with the MI-CBT and MI-CBT + CC groups showing significant reductions in more substance use outcomes (heavy drinking, cocaine use, overall illicit drug use) than the E-TAU group. The only significant group x time interaction was for partner physical aggression by men (those in the MI-CBT + CC group showed a significantly greater decrease from baseline to follow-up). Also, neither the MI-CBT nor MI-CBT + CC groups reported any injuring of partners during the follow-up. For heavy drinking, cocaine, marijuana and overall illicit drug use, there were significant reductions over time, but no group by time interaction effects. The findings illustrate significant reductions in aggression and substance use over time for those involved in VA SUD treatment, and a potential modest benefit of additional integrated treatment approaches (MI-CBT, MI-CBT + CC) on reducing aggression. Future studies should examine dissemination efforts in the VA, cost-effectiveness, and moderators of outcome.


Relation of Helicobacter pylori infection and lifestyle to the risk of chronic atrophic gastritis: a cross-sectional study in Japan.
To examine the mutual association of risk factors for both Helicobacter pylori (H. pylori) infection and chronic atrophic gastritis (CAG), a cross-sectional study on 954 residents of a rural town in Japan was conducted. Using an unconditional logistic model, we calculated the odds ratios (ORs) for H. pylori infection according to each lifestyle, as well as the ORs for CAG according to each lifestyle and H. pylori infection. A significant positive association was observed between H. pylori infection and the risk of CAG (OR = 6.29). On the other hand, a significant negative association was observed between high consumption of light-colored vegetables and the risk of CAG (OR = 0.68). We also used a path analysis to examine the direct relations of gender, age, and lifestyle variables to CAG, as well as the indirect relations of these variables to CAG through H. pylori infection. Aging had a significantly direct positive association with CAG. Although aging also had an indirect positive association with CAG through H. pylori infection, aging had no association with the consumption of light-colored vegetables. The high consumption of light-colored vegetables showed no association with H. pylori infection but had a significantly direct negative association with CAG. The results of this study suggest a possibility that high light-colored vegetables consumption contributes to the prevention of CAG.


Risk and protective factors for breast cancer in Midwest of Brazil.
Patterns of physical activity, body composition, and breastfeeding are closely related to health and are influenced by environmental, economic, and social factors. With the increase of sedentary lifestyle and overweight, many chronic diseases have also increased, including cancer. Breast cancer is the most common cancer in women worldwide, and the knowledge of its risk and protective factors is important to the adoption of primary prevention strategies. We aimed to investigate some risk and protective factors for breast cancer among women from Midwest Brazil. It is a case-control study of outpatient basis, carried out with 93 breast cancer cases and 186 controls. Socioeconomic, gynecological, anthropometric, and lifestyle variables were collected, and odds ratios (ORs) values were estimated (significance level, 5%; confidence interval (CI), 95%). Per capita income equal to or lower than 1/2 Brazilian minimum wage (OR = 1.88; CI = 1.06-3.29), residence in rural area (OR = 4.93; CI = 1.65-14.73), and presence of family history of breast cancer (OR = 5.38; CI = 1.46-19.93) are risk factors for breast cancer. In turn, physical activity (past 6 months) (OR = 0.23; CI = 0.10-0.55) and leisure physical activity at 20 years old (OR = 0.13; CI = 0.03-0.54) are protective factors for the disease in women who live in Midwest of Brazil.


Laterality of lesions and trait-anxiety on working memory performance.
An asymmetry of anterior cerebral activation favoring the right hemisphere has been associated with dispositional negative affect including trait-anxiety, while the opposite appears true of cerebral asymmetry favoring the left hemisphere. It was hypothesized that an asymmetry of cerebral activation, as defined by scores on a measure of trait-anxiety, ipsilateral to the side of an anterior brain lesion would be associated with less efficient cognitive processing than greater activation in the hemisphere contralateral to the lesion. Patients with anterior left (n = 16) or right (n = 15) hemisphere lesions completed the State-Trait Anxiety Inventory and several neurocognitive tasks. Of the abilities tested, only Digit Span scores showed an interaction between side of lesion and presumed activation asymmetry. Patients with right- but not with left-hemisphere damage showed significant differences in working memory performance depending on the presumed direction of asymmetry of the two hemispheres, supporting the dual roles of the right hemisphere in affective processing and directed attention.


The use of temporary anchorage devices for molar intrusion.
This article reviews the use of temporary anchorage devices (TADs) for maxillary molar intrusion. The authors reviewed clinical, radiographic and histologic studies and case reports. The studies provided information regarding the application, placement and biological response of orthodontic TADs. TAD-supported molar intrusion is controlled and timely and may be accomplished without the need for full-arch brackets and wires. Supraerupted maxillary first molars can be intruded 3 to 8 millimeters in 7.5 months (approximately 0.5-1.0 mm per month), without loss of tooth vitality, adverse periodontal response or radiographically evident root resorption. True molar intrusion can be achieved successfully with orthodontic TADs, re-establishing a functional posterior occlusion and reducing the need for prosthetic crown reduction.


Sleep quality, sleep propensity and academic performance.
We examined associations between measures of sleep propensity on the Epworth Sleepiness Scale, sleep quality on the Pittsburgh Sleep Quality Index and academic performance by GPA and grades in introductory psychology for 414 students. In the total sample, neither sleep propensity nor sleep quality correlated with GPA or introductory psychology grades. However, among students carrying a full course load, those reporting poor sleep quality performed less well on academic measures than those reporting a better quality of sleep. Further research is needed to assess the moderating influence of overall demands of daytime functioning on the association between sleep quality and academic performance.


Quantifying the Influence of Larval Density on Disease Transmission Indices in Culex quinquefasciatus, the Major African Vector of Filariasis.
Larval crowding is one of the abiotic factors affecting biological fitness in mosquitoes. This study aims at elucidating, quantitatively, the influence of more larval crowding on aspects of fitness in Culex quinquefasciatus mosquito. To this end, day-old larvae of the species were reared in 4 density regimens equivalent to 1 larva in 1.25, 2.5, 5, and 10 mL of distilled water. Developmental indices, adult fitness indices, and accumulation and utilisation of teneral reserves for metamorphosis were determined at these density regimens. The results revealed varying significant negative effects of larval density on all fitness indices measured for the species. The study also revealed high utilisation of teneral reserves for metamorphosis at high larval densities. The information generated will be useful in making informed-decisions in allocating scare resources for vector control, although field trials are advocated to establish these laboratory findings.


The effects of increasing body mass index on heartburn severity, frequency and response to treatment with dexlansoprazole or lansoprazole.
Higher body mass index (BMI) is a recognised risk factor for gastro-oesophageal reflux disease (GERD). Data regarding the impact of BMI on proton pump inhibitor (PPI) therapy are conflicting. To assess the impact of BMI on baseline heartburn symptom severity and frequency and response to PPI therapy in patients with non-erosive GERD (NERD) or erosive oesophagitis (EO). In post hoc analyses of phase 3 trial data, 621 NERD and 2692 EO patients were stratified by BMI (<25, 25 to <30 and ≥30 kg/m(2) ). NERD patients received either dexlansoprazole MR 30 mg or placebo daily for 4 weeks. EO patients received either dexlansoprazole MR 60 mg or lansoprazole 30 mg for 8 weeks. Symptom frequency and severity were assessed at baseline and subsequently by daily diary. In both the NERD and EO cohorts, baseline heartburn severity increased with increasing BMI. The impact of PPI therapy on the reduction in heartburn symptom frequency and severity in both NERD and EO patients was similar across BMI categories. EO healing rates in patients treated with dexlansoprazole but not lansoprazole were higher in obese patients compared with those with a BMI <30 kg/m(2) . Differences between the PPIs were small. The PPIs evaluated in this study reduced the frequency and severity of 24-h heartburn regardless of baseline BMI. In addition, because patients with higher BMI have more severe symptoms at baseline, they may experience greater therapeutic gain with dexlansoprazole (NERD and erosive oesophagitis) and possibly lansoprazole (erosive oesophagitis) treatment.


Effect of the pat, fk, stpk Gene Knock-out and mdh Gene Knock-in on Mannitol Production in Leuconostoc mesenteroides.
Leuconostoc mesenteroides can be used to produce mannitol by fermentation, but the mannitol productivity is not high. Therefore, in this study modify the chromosome of Leuconostoc mesenteroides by genetic methods to obtain high-yield strains of mannitol production. In this study, gene knock-out strains and gene knock-in strains were constructed by a two-step homologous recombination method. The mannitol productivity of the pat gene (which encodes phosphate acetyltransferase) deleteon strain (Δpat::amy), fk gene (which encodes fructokinase) deleteon strain (Δfk::amy) and stpk gene (which encodes serine-threonine protein kinase) deleteon strain (Δstpk::amy) were all increased compared to the wild type, and the productivity of mannitol for each strain was 84.8%, 83.5% and 84.1% respectively. The mannitol productivity of the mdh gene (which encodes mannitol dehydrogenase) knock-in strains (Δpat::mdh, Δfk::mdh and Δstpk::mdh) was increased to a higher level than that of the single-gene deletion strains, and the productivity of mannitol for each was 96.5%, 88% and 93.2%, respectively. The multi-mutant strain ΔdtsΔldhΔpat::mdhΔstpk::mdhΔfk::mdh had mannitol productivity of 97.3%. This work shows that multi-gene knock-out and gene knock-in strains have the greatest impact on mannitol production, with mannitol productivity of 97.3% and an increase of 24.7% over wild type. This study used the methods of gene knock-out and gene knock-in to genetically modify the chromosome of Leuconostoc mesenteroides. It is of great significance that we increased the ability of Leuconostoc mesenteroides to produce mannitol and revealed its broad development prospects.


Toward a multimodal communication theory of psychotherapy: the vicarious coprocessing of experience.
"Talking" therapy is examined as an interpersonal transaction. The personal-experience narrative is used as a vehicle through which the patient and therapist coprocess a mutual experience. Within the narrative transaction, the patient is able to vicariously re-experience and reconfigure the narrated events as he/she believes the therapist is experiencing them. Nonverbal symbolic modes of communication such as music, movement, and art also provide media through which patients and therapists can coprocess a mutual experience. The vicarious coprocessing of experience is a therapeutic factor common to talking therapy, music therapy, art therapy, movement therapy, conventional social interaction, and some healing practices in other cultures.


Plasmid releasing multiple channel bridges for transgene expression after spinal cord injury.
The regeneration of tissues with complex architectures requires strategies that promote the appropriate cellular processes, and can direct their organization. Plasmid-loaded multiple channel bridges were engineered for spinal cord regeneration with the ability to support and direct cellular processes and promote gene transfer at the injury site. The bridges were manufactured with a gas foaming technique, and had multiple channels with controllable diameter and encapsulated plasmid. Initial studies investigating bridge implantation subcutaneously (SC) indicated transgene expression in vivo for 44 days, with gene expression dependent upon the pore size of the bridge. In the rat spinal cord, bridges implanted into a lateral hemisection supported substantial cell infiltration, aligned cells within the channels, axon growth across the channels, and high levels of transgene expression at the implant site with decreasing levels rostral and caudal. Immunohistochemistry revealed that the transfected cells at the implant site were present in both the pores and channels of the bridge and were mainly identified as Schwann cells, fibroblasts, and macrophages, in descending order of transfection. This synergy between gene delivery and the scaffold architecture may enable the engineering of tissues with complex architectures.


Hypoglycemic effect of camel milk powder in type 2 diabetic patients: A randomized, double-blind, placebo-controlled trial.
Fresh camel milk was widely accepted to help to prevent and control of diabetes, especially in Africa, Middle East, and cooler dry areas of Asia. In this study, type 2 diabetic patients were enrolled to supplement with 10 g of camel milk powder twice a day for 4 weeks (n = 14), cow milk powder served as the placebo (n = 13). It was found that camel milk supplement decreased fasting blood glucose, 2-hr postprandial blood glucose, serum content of total cholesterol, resistin, and lipocalin-2. There was also a significant increase in serum content of osteocrin, amylin, and GLP-1in camel milk group, indicating an improvement on adipose tissue and skeletal muscle. Camel milk powder supplement significantly enriched the relative abundance of Clostridium_sensu_stricto_1 and [Eubacterium]_eligens_group compared with cow milk after the 4-week intervention. This study suggested that camel milk powder can be used as a functional food help to treat type 2 diabetes.


Effect of Bone Powder/Mesenchymal Stem Cell/BMP2/Fibrin Glue on Osteogenesis in a Mastoid Obliteration Model.
This study aimed to prospectively compare the osteogenesis of bone powder (BP) substances with and without mesenchymal stem cells (MSCs) and evaluate the synergistic effect of topically applied recombinant human bone morphogenic protein-2 (BMP2) on MSC-loaded BP using fibrin glue in a mastoid obliteration model. To determine the expression of osteocyte-specific genes, total RNA was isolated from three MSC groups: Untreated MSCs, MSCs cultured with BP, and MSCs cultured with BP and BMP2. Real-time polymerase chain reaction was carried out with specific primers of osteogenesis-related genes runt-related transcription factor 2, osteocalcin, osteoprotegerin, osterix, alkaline phosphatase, transforming growth factor beta, and type I collagen. Live/dead staining was also performed. To observe the adhesion of MSCs to the BP, MSCs were treated with BP for 2 days and the surface was observed by scanning electron microscopy (SEM). Under general anesthesia, mastoid obliteration was performed in rats using three groups: treated with BP alone, BP/MSCs, and BP/MSC/BMP2. Before decapitation at 8 weeks post operation, in vivo micro computed tomography (micro CT) was performed. The bullae were dissected, fixed, and decalcified. followed by dehydration, paraffin embedding, and staining by hematoxylin and eosin and Masson's trichrome. SEM showed the MSCs to be well-attached to the superficial area of the BP. The expression of osteocyte-specific genes was the highest in the MSCs cultured with BP and BMP2, followed by cultured with BP only, and untreated MSCs. The BP/MSC/BMP2 group showed the highest radiodensity of bullae in microCT analysis. The microCT findings revealed that the BP/MSC/BMP2 group showed the most enhanced osteogenesis of the scaffold compared to the other two groups. No significant difference was found in osteoconductive osteogenesis between the control and BP/MSC groups. However, the BP/MSC/BMP2 group showed significantly enhanced osteoconductive osteogenesis and osteoinductive change of the BP as shown by hematoxylin and eosin staining. Histomorphometry of osteogenesis revealed that the difference between the BP/MSC/BMP2 group and the other two groups was statistically significant. A small amount of BMP2 is necessary during MSC loading to enhance the osteogenesis of BP and avoid complications associated with high doses of BMP2. These results may be applicable to mastoid obliteration in clinical practice.


Expression of 4-hydroxynonenal in esophageal squamous cell carcinoma.
Esophageal squamous cell carcinoma (ESCC) is one of the most common types of cancer in Asia, particular in China. However, the pathogenesis of ESCC has not previously been well demonstrated. A major product of lipid peroxidation, 4-hydroxynonenal (4-HNE), is considered to be an oxidative stress inducer, as it is involved in the pathogenesis of a number of degenerative diseases, including Alzheimer's disease, atherosclerosis, cataracts and cancer. In order to investigate the association between oxidative stress and the pathogenic process of ESCC, the present study determined the expression levels of 4-HNE in 23 non-malignant esophageal epithelial tissues, 11 esophageal carcinoma in situ tissues and 57 ESCC tissues from patients in the Chaoshan area, a high-risk region for esophageal cancer in China. A significantly higher expression level of 4-HNE was identified in ESCC tissues compared with that in non-malignant esophageal epithelial tissues (P<0.05). Furthermore, immunohistochemical analysis demonstrated that expression levels of 4-HNE were significantly associated with the clinical stage. The patients with positive staining of 4-HNE revealed a poorer clinical outcome compared with that of patients with negative staining. 4-HNE was significantly associated with the severity of inflammation and increased with the progression of precancerous lesions (P<0.05). These results provide pathological evidence that oxidative stress is a driving force of ESCC carcinogenesis.


Switching photorelease to singlet oxygen generation by oxygen functionalization of phenothiazine photocages.
A phenothiazine-based photoremovable protecting group (PRPG) for single and dual release of carboxylic acids was developed. The change in the oxidation state of the sulfur atom of the phenothiazine PRPG resulted in singlet oxygen generation, rather than photorelease. The difference in the photochemistry between oxygen-free and oxygen-functionalized phenothiazine was investigated and supported by DFT calculations.


Donor killer immunoglobulin-like receptor genes and reactivation of cytomegalovirus after HLA-matched hematopoietic stem-cell transplantation: HLA-C allotype is an essential cofactor.
Natural killer (NK) cells whose killer immunoglobulin-like receptors (KIRs) recognize human leukocyte antigen (HLA) ligand are "licensed" for activity. In contrast, non-licensed NK cells display KIRs for which ligand is absent from the self genotype and are usually hyporesponsive. Surprisingly, non-licensed cells are active in tumor control after hematopoietic stem-cell transplantation (HSCT) and dominate NK response to murine cytomegalovirus (CMV) infection. From those reports, we hypothesized that control of human CMV early after HSCT is influenced by donor KIR genes whose HLA ligand is absent-from-genotype of HLA-matched donor and recipient. To investigate, we studied CMV reactivation through Day 100 after grafts involving CMV-seropositive donor and/or recipient. A multivariate proportional rates model controlled for variability in surveillance and established covariates including acute graft-versus-host disease; statistical significance was adjusted for testing of multiple KIRs with identified HLA class I ligand (2DL1, 2DL2/3, 2DS1, 2DS2, full-length 2DS4, 3DL1/3DS1, 3DL2). Among HSCT recipients (n = 286), CMV reactivation-free survival time varied with individual donor KIR genes evolutionarily specific for HLA-C: when ligand was absent from the donor/recipient genotype, inhibitory KIRs 2DL2 (P < 0.0001) and 2DL1 (P = 0.015) each predicted inferior outcome, and activating KIRs 2DS2 (P < 0.0001), 2DS1 (P = 0.016), and 2DS4 (P = 0.016) each predicted superior outcome. Otherwise, with ligand present-in-genotype, donor KIR genes had no effect. In conclusion, early after HLA-matched HSCT, individual inhibitory and activating KIR genes have qualitatively different effects on risk of CMV reactivation; unexpectedly, absence of HLA-C ligand from the donor/recipient genotype constitutes an essential cofactor in these associations. Being KIR- and HLA-C-specific, these findings are independent of licensing via alternate NK cell receptors (NKG2A, NKG2C) that recognize HLA-E.


Endoscopic transsphenoidal approach in resection of intracranial clivus chondrosarcoma: A case report.
Intracranial primary chondrosarcomas are rare, accounting for <0.15% of all intracranial tumors, but exhibit a high risk of recurrence. Due to the rarity of this condition, it has proven difficult to establish efficacy-based treatment guidelines. The present study details a case of clivus chondrosarcoma exhibiting no recurrence following surgical resection using an endoscopic transsphenoidal approach and postoperative adjuvant radiotherapy. A 41-year-old female presented with primary symptoms of left eye esotropia, scotoma of the left nasal visual field and double vision. Preoperative cranial magnetic resonance imaging revealed a lesion on the clivus, which was initially diagnosed as chordoma. However, clivus chondrosarcoma was ultimately diagnosed based on intraoperative findings and postoperative histopathology. The tumor was totally resected and 25 doses of adjuvant radiotherapy with planning gross tumor volume (60 Gy) and planning clinical target volume (50 Gy) were administered for 5 weeks. The patient was discharged at 12 days post-surgery with no obvious postoperative complications. Over the 28-month follow-up period, there was no evidence of recurrence, which may be due to the successful use of combined gross total resection and adjuvant radiotherapy. Therefore, surgical resection using an endoscopic transsphenoidal approach and postoperative adjuvant radiotherapy is an effective method for treating intracranial clivus chondrosarcoma.


[Surgical management of coronary artery fistula with tricuspid stenosis in a three-month-old infant].
This is a case report of a 3-month-old infant who had been suffering from progression of cardiac failure. Two dimensional echo-cardiography revealed a fistula between the right coronary artery to the right heart. He was operated upon using extracorporeal circulation. Symbas procedure was carried out to close the fistula. Upon opening the right atrium, there noted tricuspid stenosis (TS). Then, ASD was created to reduce the right atrial pressure to prevent right heart failure secondary to TS. He is doing well postoperatively.


The application of double fluorescence to the rapid selection of atypical cervical epithelial cells spread in monolayers.
Monolayer spreads of cervical cells were prepared and reacted in sequence with two fluorescent probes. The nuclei were reacted with 4,6-Diamidino-2-phenylindole (DAPI), resulting in white fluorescence of all cell nuclei. Those cells possessing active guanidinobenzoatase (GB) bound the second probe, rhodamine-alpha-N-agmatine (Rh-Agm), resulting in orange cell surface fluorescence. Atypical epithelial cells possessed both active GB and enlarged nuclei; such cells could easily be recognised by their cytological appearance. We illustrate our results in the form of colour prints which are representative of our observations of cells in both normal and abnormal cervical spreads.


Iatrogenic Middle Cerebral Artery Ruptured Pseudoaneurysm Successfully Treated With a Pipeline Embolization Device.
Background: Endovascular advances have shifted the treatment algorithms for traumatic intracranial pseudoaneurysms (IPs) from vessel sacrifice to reconstruction. The Pipeline embolization device (PED) is a flow-diverting stent that promotes endothelialization across the lesion and reconstitutes the parent vessel lumen. Case Report: A 66-year-old male with a history of a right orbital apex lesion presented for biopsy with ophthalmology. Ophthalmology performed a right lateral orbitotomy complicated by brisk arterial bleeding from a proximal right middle cerebral artery (MCA) pseudoaneurysm. The MCA pseudoaneurysm was treated endovascularly with a PED, resulting in immediate stasis of contrast within the lesion without compilation. Interval follow-up angiograms 6 weeks and 6 months after the procedure showed no evidence of recurrence and a widely patent stent. Conclusion: The PED provided a rapid, minimally invasive, and durable treatment option for an acutely ruptured IP. We illustrate that endovascular management with flow diversion can be effectively used in select cases and provides a way to reconstruct the damaged vessel lumen and obliterate the aneurysm.


[Effects of fuzheng huayu recipe in antagonizing rat's renal interstitial fibrosis].
To observe the effects of Fuzheng Huayu Recipe (FHR) on rat's renal interstitial fibrosis induced by mercuric chloride (HgCl2), and to explore preliminarily its mechanism of action. Rats were randomly divided into four groups: the normal group, the model group, the FHR group and the vitamin E group, the latter two were treated respectively by FHR 4.6 g/kg and vitamin E 100 mg/kg. Rats model was established by oral administration of 8 mg/kg HgCl2 for 9 weeks. Serum creatinine (Cr) and urea nitrogen (BUN) content were tested with corresponding test kits; hydroxyproline (Hyp) content in kidney was assayed with hydrochloric acid hydrolysis; renal histologic change was observed with HE, Masson and methenamine silver (PASM) staining; and collagen type I (Col I), as well as protein expressions of fibronectin (FN) and alpha-smooth muscle actin (alpha-SMA) was determined with Western blot. Compared with the model group, the kidney/body weight ratio, serum levels of Cr and BUN, kidney Hyp content, and severity of renal interstitial fibrosis in the two treated groups were significantly lower (P<0.05 or P<0.01), and the improvements were more significant in the FHR group than those in the vitamin E group; Col I and FN protein expression was also weaker in the two treated group (Col, P<0.05; FN, P<0.01); while the expression of alpha-SMA was lower in the FHR group (P<0.01), but it wasn't in the vitamin E group (P>0.05). FHR could improve the HgCl2-induced renal function injury in rats, decrease extracellular matrix deposition and restrain renal interstitial fibrosis, the mechanism of action might be related with its inhibitory effect on myofibroblast activation.


Management of symptomatic benign prostatic hyperplasia--today.
Symptomatic benign prostatic hyperplasia (BPH) is one of the commonest causes today of men presenting with lower urinary tract symptoms (LUTS). We can find this in 50% of men over the age of fifty. If BPH is not treated, then one can expect that the disease will progress in a significant number of individuals. What we need to do is try to predict based on certain baseline parameters such as International Prostate Score (IPSS), prostate volume, prostate-specific antigen (PSA) and the degree of bother, those men to whom we should offer therapy. The other consideration is that combination therapy of a 5-alpha reductase inhibitor (5-ARI) and an alpha blocker, may provide the best results in the prevention of progression of the disease or ultimately, the need for surgery. The final considerations are if, for how long and for whom should combination therapy be utilized.


Relationship of surveillance cultures to bacteremia and fungemia in bone marrow transplant recipients with Hickman or Broviac catheters.
A total of 64 episodes of bacteremia and fungemia were documented in 25 allogeneic bone marrow transplant recipients. Coagulase-negative staphylococci were the most common pathogens recovered, with 34 of the 39 isolated being methicillin resistant. Streptococcus viridans (11 episodes), diphtheroids (5 episodes), and Pseudomonas aeruginosa (4 episodes) accounted for the majority of the other pathogens causing bacteremia. Six episodes of fungemia were also seen. Coagulase-negative staphylococci were demonstrated in 31 of 36 (86%) throat cultures, 25 of 35 (71%) stool cultures, and 6 of 7 (86%) Hickman or Broviac catheter exit site surveillance cultures prior to the development of bacteremia caused by these organisms. Throat surveillance cultures positive for S. viridans also showed a correlation (88%) with subsequent S. viridans bacteremia. However, surveillance cultures for aerobic gram-negative bacilli, diphtheroids, and fungi did not correlate with subsequent septicemia. Organisms isolated in throat surveillance cultures correlated with subsequent bacteremia caused by these organisms in only 15% of all the cultures taken, while only 14% of stool cultures predicted bacteremia. The utility of surveillance cultures is limited because of low cost-effectiveness and a high rate of false-positive results.


[Absence of frontal lobe dysfunction and working memory deficits in young schizophrenic patients].
The impairment in tasks requiring intact frontal lobe functions has been repeatedly shown in schizophrenics. However, the relative roles of confounding factors, like duration of the disease, social withdrawal, or antidopaminergic medication, are not clearly demonstrated. We studied the performance of 12 young active patients, with chronic residual schizophrenia that had recent onset, and 12 control subjects, with frontal lobe tests and with a battery designed to explore working memory. The results show normal performance in schizophrenia. The small number of patients does not allow definitive conclusions, but this study suggests that a frontal dysfunction may not be present early in the evolution of schizophrenia in active patients.


[The risks of anesthesia in obstetric interventions].
In obstetric anaesthesia, general anaesthesia combined with endotracheal intubation, spinal anaesthesia and peridural anaesthesia is used. The main risks of general anaesthesia are: difficult intubation, aspiration of acid gastric content in non-fasting patients, depression of the fetus with narcotics and the occurrence of awareness of the mother. The main dangers of spinal anaesthesia are: hypotension of the mother leading to reduced utero-placentar blood flow due to sympathetic block, post-spinal headache and vomiting. The specific risks of peridural anaesthesia are: maternal hypotension, the possibility of inadvertent intravenous injection of local anaesthetics leading to cardiac and cerebral intoxication, inadvertent intrathecal application of local anaesthetics followed by total spinal block which requires reanimation and inadvertent dura perforation followed by long-lasting headache. Most anaesthesia-related maternal deaths by far occur during Caesarean section performed under general anaesthesia, but at present there is no clear evidence that the anaesthetic risk of spinal or peridural anaesthesia, on the one hand, is lower than that one of general anaesthesia, on the other.


[The place of aldosterone receptor blockers in the treatment of chronic heart failure].
The paper contains presentation of basics of clinical pharmacology of aldosterone receptor blockers specifically that of spironolactone and eplerenone, and discussion of results of 2 large randomized placebo controlled trials which showed that long term use of aldosterone receptor blockers allowed to improve prognosis of patients with severe chronic heart failure and postinfarction systolic left ventricular dysfunction, and to reduce requirements in repetitive hospitalizations.


Integrating mindfulness into the extended process model of emotion regulation: The dual-mode model of mindful emotion regulation.
Extensive research has been conducted regarding how people manage their emotions. Within this research, there has been growing attention toward the role of mindfulness in emotion regulation. While prior reviews have discussed mindfulness in the context of emotion regulation, they have not provided a thorough integration using the prevailing models of emotion regulation or mindfulness. The present review discusses the Extended Process Model of Emotion Regulation and Monitoring and Acceptance Theory of mindfulness in order to propose a novel integrated framework, the Dual-mode Model of Mindful Emotion Regulation (D-MER). This model proposes two "modes" of mindfulness: Implementation and facilitation. Implementation posits that mindfulness skills can be used as emotion regulation strategies through attentional deployment and cognitive change. Facilitation posits that mindfulness as a state or trait affects emotion generation and regulation through effects on cognitive processes and positive or negative valence systems. Further, the D-MER posits that mindfulness experience can improve the efficiency of mindfulness-based emotion regulation strategies (implementation) while effects of mindfulness on emotion regulation processes become increasingly trait-like and automatic over time (facilitation). Empirical and theoretical support for this model are discussed, specific hypotheses to guide further research are provided, and clinical implications are presented. Use of this model may identify mechanisms underlying the interaction between mindfulness and emotion regulation which can be used in ongoing affective and clinical research. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Hemodynamic and metabolic effects of extracranial carotid disease.
Cerebral blood flow (CBF), cerebral blood volume (CBV), the CBF/CBV ratio - an index of the hemodynamic reserve capacity - the rate of oxygen metabolism (CMRO2), and the fractional extraction of oxygen by the brain (OEF) were studied by positron emission tomography (PET) in the cortical territory of both internal carotid arteries in 15 cases of transiently symptomatic or progressive extracranial atherosclerotic carotid disease. None of the patients had a major stroke or had a significant neurological deficit except 1 whose damaged hemisphere is excluded from study. All were asymptomatic at the time of PET scanning. Values were obtained in the middle cerebral artery (MCA) distribution, and in the anterior and posterior borderzone regions. Eight cases had unilateral carotid stenosis of 80% or greater and 7 had unilateral or bilateral occlusion of the origin of the internal carotid artery. Results obtained in patients were compared using Student's t-test, to those obtained in neurologically normal, elderly volunteers. Patients with carotid stenosis had a significantly decreased CBF (p less than .025) and CBF/CBV ratio (p less than .025) selectively in the anterior borderzone regions. This was accompanied by a trend toward elevated OEF and declining CMRO2 values. Patients with carotid occlusion had significantly decreased CBF (p less than .005), decreased CBF/CBV ratio (p less than .005) and decreased CMRO2 (p less than .025) in the ipsilateral anterior borderzone and MCA territories. Similar changes were present in the opposite hemisphere of patients with bilateral carotid disease. These results indicate that carotid stenosis is associated with hypoperfusion and diminished hemodynamic reserve capacity in the anterior borderzone, and that carotid occlusion produces more widespread hypoperfusion and metabolic depression.


[The clinical characteristics of etiologies, diagnoses and treatment of emergency gastrointestinal hemorrhage.].
To investigate the causes, clinical features, treatment and prognosis of gastrointestinal bleeding (GIB) patients in emergency department. To analyze prospectively the clinical data of 168 GIB patients admitted to the emergency department of Peking Union Medical College Hospital during 2006.1 - 2006.12. (1) General data: male:female = 1.75:1 (107:61), mean age 13 - 87 (56.5 +/- 17.8) years with a peak in 60 - 69 years. The percentage of old patients was significantly higher than that of young and middle age (52.4% vs 19.6% and 28.0%, P = 0.000). (2) The incidence of acute gastric mucosal lesion in patients taking non-steroidal antiinflammatory drugs (NSAIDs) (18.5%) was significantly higher than that in patients not taking (0.7%, P = 0.000). (3) 86.9% (146/168) of the patients had anemia. (4) More patients who took emergency gastroscopy could be diagnosed than those patients who did not (89.4% vs 58.5%, P = 0.000), while no significant difference could be seen between patients who took emergency enteroscopy and patients who had non-emergency gastroscopy (20.0% vs 57.9%, P = 0.315). (5) The hemostatic ratio in GIB patients due to peptic ulcer was obviously higher than that in GIB patients due to other causes (86.0% vs 40.7%, P = 0.000). The rate of emergency operation for GIB patients was 1.8%. Most of the GIB patients admitted to tertiary general hospitals are elderly males. NSAIDs administration is one of the most important causes of upper GIB. Upper GIB patients should have gastroscopy as soon as possible, while emergency coloscopy is of little significance in cases with lower gastrointestinal hemorrhage.


The animal sensorimotor organization: a challenge for the environmental complexity thesis.
Godfrey-Smith's environmental complexity thesis (ECT) is most often applied to multicellular animals and the complexity of their macroscopic environments to explain how cognition evolved. We think that the ECT may be less suited to explain the origins of the animal bodily organization, including this organization's potentiality for dealing with complex macroscopic environments. We argue that acquiring the fundamental sensorimotor features of the animal body may be better explained as a consequence of dealing with internal bodily-rather than environmental complexity. To press and elucidate this option, we develop the notion of an animal sensorimotor organization (ASMO) that derives from an internal coordination account for the evolution of early nervous systems. The ASMO notion is a reply to the question how a collection of single cells can become integrated such that the resulting multicellular organization becomes sensitive to and can manipulate macroscopic features of both the animal body and its environment. In this account, epithelial contractile tissues play the central role in the organization behind complex animal bodies. In this paper, we relate the ASMO concept to recent work on epithelia, which provides empirical evidence that supports central assumptions behind the ASMO notion. Second, we discuss to what extent the notion applies to basic animal architectures, exemplified by sponges and jellyfish. We conclude that the features exhibited by the ASMO are plausibly explained by internal constraints acting on and within this multicellular organization, providing a challenge for the role the ECT plays in this context.


Similar hypercoagulable state and thrombosis risk in type I and type III protein S-deficient individuals from mixed type I/III families.
Protein S, which circulates in plasma in a free and bound form, is an anticoagulant protein that stimulates both activated protein C (APC) and tissue factor pathway inhibitor (TFPI). Hereditary type I protein S deficiency (low total and low free protein S) is a well-established risk factor for venous thrombosis, whereas the thrombosis risk associated with type III deficiency (normal total and low free protein S) has been questioned. Kaplan-Meier analysis was performed on 242 individuals from 30 families with protein S deficiency. Subjects were classified as normal, type I deficient or type III deficient according to their total and free protein S levels. Genetic and functional studies were performed in 23 families (132 individuals). Thrombosis-free survival was not different between type I and type III protein S-deficient individuals. Type III deficient individuals were older and had higher protein S, TFPI and prothrombin levels than type I deficient individuals. Thrombin generation assays sensitive to the APC- and TFPI-cofactor activities of protein S revealed similar hypercoagulable states in type I and type III protein S-deficient plasma. Twelve PROS1 mutations and 2 large deletions were identified in the genetically characterized families. Not only type I, but also type III protein S deficiency is associated with a hypercoagulable state and increased thrombosis risk. However, these findings may be restricted to type III deficient individuals from families with mixed type I/III protein S deficiency, as these represented 80% of type III deficient individuals in our cohort.


Compact reconfigurable on-chip polarization beam splitters enabled by phase change material.
In this paper, we present the design of a compact reconfigurable polarization beam splitter (PBS) enabled by ultralow-loss phase-changing Sb2Se3. By harnessing the phase-change-mediated mode coupling in a directional coupler (DC), guided light with different polarizations could be routed into different paths and this routing could be dynamically switched upon the phase change of Sb2Se3. With an optimized DC region, the proposed PBS demonstrates efficient polarization splitting with crosstalk less than -21.3 dB and insertion loss less than 0.16 dB at 1550 nm for both phase states of Sb2Se3, and features energy efficient property benefitting from the nonvolatile phase change of Sb2Se3, which holds great potentials for on-chip applications involving polarization control, including polarization-division multiplexing system, quantum photonics, microwave photonics, etc.


Murine Schistosoma bovis infection: analysis of parasitic and immune parameters.
Humoral and cellular responses to Schistosoma bovis antigens have been evaluated over a period of 11 weeks in mice exposed to S. bovis cercariae and data analysed in the context of the parasitic parameters (worm and egg loads) recorded at days 30, 60 and 80 of the ongoing infection. Results revealed a decrease of worm burden, particularly marked for female worms, between day 60 and day 80 of infection suggesting a higher susceptibility of female schistosomes to attrition mechanisms. The B-cell response, studied by measuring the production of different isotypes, was directed against different stage specific antigens, with a predominance of IgG1 antibodies associated with a significant increase of IgA and IgE antibodies after egg deposition. The T-cell response, assessed after in vitro stimulation of splenocytes, showed a predominant production of Th-2 cytokines (IL-4, IL-5 and IL-10) occurring after egg laying. Interestingly in contrast to S. mansoni infection the Th-2 polarization did not seem to be exclusively triggered by egg-associated antigens since significant amounts of IL-10 were produced after stimulation with adult worm antigen preparation (SWAP) before the beginning of egg deposition.


Tissue factor deficiency and PAR-1 deficiency are protective against renal ischemia reperfusion injury.
Ischemia/reperfusion (IR) injury is a leading cause of acute renal failure and an important contributor to allograft damage. Tissue factor (TF) is up-regulated during IR, and TF inhibition reduces renal injury. However, the underlying mechanisms by which TF contributes to injury have not been elucidated. We postulated that TF contributes to IR injury by production of coagulation proteases and subsequent signaling by protease activated receptor (PARs). We compared renal injury after 25 minutes of bilateral renal ischemia and varying periods of reperfusion in C57BL/6 mice, those expressing low levels of TF (low-TF), hirudin-treated C57BL/6, and mice lacking either PAR-1 or PAR-2. C57BL/6 mice developed severe renal failure and died within 48 hours of reperfusion. In contrast, low-TF, hirudin-treated C57BL/6, and PAR-1-/- mice were protected from renal failure and had reduced mortality, tubular injury, neutrophil accumulation, and lower levels of the chemokines KC and MIP-2. Importantly, PAR-1-/- mice had lower chemokine levels despite up-regulation of TF and fibrin deposition. In addition, treating PAR-1-/- mice with hirudin conferred no additional benefit. Somewhat surprisingly, PAR-2 deficiency did not protect from renal failure. These experiments indicate that increased TF activity after renal IR leads to increased CXC chemokine expression and subsequent neutrophil-mediated injury predominantly by thrombin-dependent PAR-1 signaling.


The effect of titanium dioxide nanoparticles on mice midbrain substantia nigra.
Widely used Titanium dioxide nanoparticles (TiO2) enter into the body and cause various organ damages. Therefore, we aimed to study the effect of TiO2 on the substantia nigra of midbrain. 40 male BALB/c mice were randomly divided into five groups: three groups received TiO2 at doses of 10, 25, and 50 mg/kg, the fourth group received normal saline for 45 days by gavage, and control group (without intervention). Then, Motor tests including pole and hanging tests were done to investigate motor disorders. The animal brain was removed for histological purposes. Accordingly, immunohistochemistry was performed to detect tyrosine hydroxylase positive cells, and then toluidine blue staining was done to identify dark neurons in the substantia nigra. Eventually, the total number of these neurons were counted using stereological methods in different groups. The results showed that the time recorded for mice to turn completely downward on the pole in the TiO2-50 group increased and also the time recorded for animals to hang on the wire in the hanging test significantly decreased (P<0.05) in comparison with other groups. Also, the average number of tyrosine hydroxylase positive neurons in TiO2-25 and TiO2-50 groups significantly decreased as compared to the TiO2-10 and control groups (P<0.05). The total number of dark neurons in the TiO2-25 and TiO2-50 groups was substantially higher than the TiO2-10, control and normal saline groups (P<0.05). Our findings indicated that TiO2, depending on dose, can cause the destruction of dopaminergic neurons and consequently increase the risk of Parkinson's disease.


Frequency stabilized lasers: optical feedback effects.
Two simple systems have been described for stabilizing the frequency of a 2-mW internal mirror 633-nm He-Ne laser. This paper shows that small amounts of optical feedback will seriously reduce their performance. Their relative sensitivity to optical feedback from a plane mirror is compared.


Tandem repeats derived from centromeric retrotransposons.
Tandem repeats are ubiquitous and abundant in higher eukaryotic genomes and constitute, along with transposable elements, much of DNA underlying centromeres and other heterochromatic domains. In maize, centromeric satellite repeat (CentC) and centromeric retrotransposons (CR), a class of Ty3/gypsy retrotransposons, are enriched at centromeres. Some satellite repeats have homology to retrotransposons and several mechanisms have been proposed to explain the expansion, contraction as well as homogenization of tandem repeats. However, the origin and evolution of tandem repeat loci remain largely unknown. CRM1TR and CRM4TR are novel tandem repeats that we show to be entirely derived from CR elements belonging to two different subfamilies, CRM1 and CRM4. Although these tandem repeats clearly originated in at least two separate events, they are derived from similar regions of their respective parent element, namely the long terminal repeat (LTR) and untranslated region (UTR). The 5' ends of the monomer repeat units of CRM1TR and CRM4TR map to different locations within their respective LTRs, while their 3' ends map to the same relative position within a conserved region of their UTRs. Based on the insertion times of heterologous retrotransposons that have inserted into these tandem repeats, amplification of the repeats is estimated to have begun at least ~4 (CRM1TR) and ~1 (CRM4TR) million years ago. Distinct CRM1TR sequence variants occupy the two CRM1TR loci, indicating that there is little or no movement of repeats between loci, even though they are separated by only ~1.4 Mb. The discovery of two novel retrotransposon derived tandem repeats supports the conclusions from earlier studies that retrotransposons can give rise to tandem repeats in eukaryotic genomes. Analysis of monomers from two different CRM1TR loci shows that gene conversion is the major cause of sequence variation. We propose that successive intrastrand deletions generated the initial repeat structure, and gene conversions increased the size of each tandem repeat locus.


A Cross-Sectional Multicentre Study to Validate Insulin Sensitivity Index Cut-Offs for Detection of Metabolic Syndrome in Indian Adolescents with Type-1 Diabetes.
A previous study compared insulin sensitivity indices for the detection of double diabetes (DD) in Indian adolescents with type-1 diabetes (T1D) and derived a cut-off to predict future risk for the development of metabolic syndrome (MS) in adolescents with T1D. We conducted the current study with the aim to validate these cut-offs for detecting DD among Indian subjects with T1D from various geographical locations. This multicentric cross-sectional study included 161 Indian adolescents with T1D. Demographic, anthropometric, clinical, and biochemical data were collected using standard protocols. Insulin sensitivity (IS) was calculated using various equations developed to determine insulin sensitivity in subjects with T1D. Metabolic syndrome was diagnosed using International Diabetes Federation (IDF) Consensus Definition 2017. We report 4.3% prevalence of MS in Indian adolescents with T1D with an additional 29.8% of study participants at risk of development of MS. Low High density lipoprotein (HDL) (23.6%) was the commonest abnormal component of the MS definition. Insulin sensitivity calculated by an equation derived by the SEARCH group was the most appropriate index to identify MS and metabolic risk in Indian adolescents with T1D. The proposed cut-off of 5.48 had high specificity, positive predictive value, and negative predictive value in identifying the risk of the development of DD. Insulin sensitivity calculated by the equation proposed by the SEARCH group together with cut-offs derived in earlier study may be used effectively to identify risk of development of MS/DD in Indian adolescents with T1D from various geographical locations.


Obtaining Acute Brain Slices.
Obtaining acute brain slices for electrophysiology or amperometric recordings has become a routine procedure in most labs in the field of neuroscience. Yet, protocols describing the step by step process are scarce, in particular for routine acute preparations such as from the mouse hippocampus. Here we provide a detailed protocol for the dissection, extraction and acute slicing of the mouse brain, including tips and list of material required.


Combined representations for frequency and duration in detection templates for expected signals.
When trying to detect a tonal signal in a continuous broadband noise, listeners attend selectively to both the frequency and the duration of the expected signal. However, it is not known whether they monitor separate or combined representations of these two attributes. To investigate this question, a probe-signal method was used to measure the detectability of signals of expected and unexpected durations at two expected frequencies. The four listeners expected only one of two signals to be presented at random: a brief tone at one frequency or a long tone at another frequency. For each signal frequency, the detectability of the signals of unexpected duration decreased to near chance as the difference between the expected and unexpected duration, at that frequency, increased. The frequency specificity of this duration tuning indicates that both the frequency and the duration of an expected stimulus are represented in a single template.


A Simple Fecal Bacterial Marker Panel for the Diagnosis of Crohn's Disease.
Background and Aims: Intestinal dysbiosis is implicated in the pathogenesis of Crohn's disease (CD). We evaluated fecal and sera microbial markers for clinical use in detecting CD. Methods: Fecal samples from 346 Asian subjects were collected, including 95 patients with CD, 81 patients with ulcerative colitis (UC), 65 patients with irritable bowel syndrome (IBS), and 105 healthy subjects (HS). Microbial indicators Fusobacterium nucleatum (Fn), Faecalibacterium prausnitzii (Fp), and Escherichia coli (E. coli) were identified based on a review of the literature. The relative abundance of the three bacterial markers were measured by qPCR, and two serological microbial markers (anti-Fn, anti-E. coli) were measured by ELISA. We evaluated the diagnostic performance of these microbial markers by ROC curve analysis. Results: The quantification of Fp, Fn, and E. coli of fecal samples is relatively stable when stored up to 6 h at room temperature. The significant increasing abundances of Fn were accompanied by a decline of Fp in the CD group. Fn exhibited a slightly higher diagnostic value than Fp in distinguishing CD from HS (Area Under Curve, AUC = 0.841 vs. 0.811) or irritable bowel syndrome (IBS) groups (AUC = 0.767 vs. 0.658), and the further combination of Fn and Fp improved the diagnostic value (HS, AUC = 0.867; IBS, AUC = 0.771). However, anti-E. coli and anti-Fn antibodies in serum did not possess diagnostic value for CD or UC. Conclusion: A combination of fecal Fn and Fp was identified as a valuable marker for CD diagnosis. A CD bacterial marker panel may provide a simple non-invasive approach to screen for CD.


Pathogenic variants in KPTN gene identified by clinical whole-genome sequencing.
Status epilepticus is not rare in critically ill intensive care unit patients, but its diagnosis is often delayed or missed. The mortality for convulsive status epilepticus is dependent on the underlying aetiologies and the age of the patients and thus varies from study to study. In this context, effective molecular diagnosis in a pediatric patient with a genetically heterogeneous phenotype is essential. Homozygous or compound heterozygous variants in KPTN have been recently associated with a syndrome typified by macrocephaly, neurodevelopmental delay, and seizures. We describe a comprehensive investigation of a 9-yr-old male patient who was admitted to the intensive care unit, with focal epilepsy, static encephalopathy, autism spectrum disorder, and macrocephaly of unknown etiology, who died of status epilepticus. Clinical whole-genome sequencing revealed compound heterozygous variants in the KPTN gene. The first variant is a previously characterized 18-bp in-frame duplication (c.714_731dup) in exon 8, resulting in the protein change p.Met241_Gln246dup. The second variant, c.394 + 1G > A, affects the splice junction of exon 3. These results are consistent with a diagnosis of autosomal recessive KPTN-related disease. This is the fourth clinical report for KPTN deficiency, providing further evidence of a wider range of severity.


Mucosal immune response to poliovirus vaccines in childhood.
Comparative evaluation of the systemic and secretory antibody response to live attenuated (oral) poliovirus vaccine ( OPV ) or inactivated poliovirus vaccine (IPV) has suggested that both vaccines are highly effective in inducing seroconversion and in preventing paralytic poliomyelitis. However, parenteral immunization with IPV does not appear to be highly effective in inducing secretory antibody response in the nasopharynx or alimentary tract during primary immunization. Reimmunization with IPV in subjects previously primed with parenterally administered IPV appears to result in a mild booster effect on the development of secretory antibody response. More significantly, rechallenge by the oral route with OPV in IPV-primed subjects resulted in a marked enhancement of secretory antibody response. In general, no suppression of systemic or secretory response to poliovirus was observed with either form ( OPV vs. IPV) or with route of immunization. These observations are discussed in relation to the immune response observed with other mucosally or parenterally administered antigens. Their implications in the development of oral tolerance are briefly reviewed.


Bilateral periventricular nodular heterotopia with megalencephaly: a case report.
Bilateral periventricular nodular heterotopia is a neuronal migration disorder characterized by gray matter cellular rests in the periventricular regions. Megalencephaly has not been reported in children with bilateral periventricular nodular heterotopia. No other disorder with a similar phenotype has been reported. Here we report the case of a 5-year-old Japanese boy with bilateral periventricular nodular heterotopia and megalencephaly. Relative macrocephaly was evident at birth, and bilateral periventricular nodular heterotopia and megalencephaly were noted on magnetic resonance imaging (MRI). However, no hydrocephalus or indication of cerebral cortical dysplasia was seen. A mild intellectual disability was present, but the patient had no history of seizures. Genetic analysis revealed no mutation on the capillary sequences for FLNA, and no pathogenic abnormalities were evident on array comparative genomic hybridization. This case could represent a new disease entity: bilateral periventricular nodular heterotopia with megalencephaly.


Cancer Pain Management Insights and Reality in Southeast Asia: Expert Perspectives From Six Countries.
This expert opinion report examines the current realities of the cancer pain management landscape and the various factors that hinder optimal pain control in six countries in Southeast Asia, describes ongoing efforts to advance patient care, and discusses approaches for improving cancer pain management. Information was gathered from leading experts in the field of cancer pain management in each country through an initial meeting and subsequent e-mail discussions. Overall, there are vast disparities in cancer pain management practices and access to opioids in the Southeast Asian countries. The experts considered cancer pain as being generally undermanaged. Access to opioids is inadequate in most countries, and opioid use for analgesia remains inadequate in the region. Several system-, physician-, and patient-related barriers to adequate pain relief were identified, including widespread over-regulation of opioid use, shortage of trained health care workers, inadequacies in pain assessment and knowledge about managing pain, and widespread resistance among patients and physicians toward opioid treatment. According to the experts, many of the ongoing initiatives in the Southeast Asian countries are related to educating patients and physicians on cancer pain management and opioid use. Efforts to improve opioid availability and reduce regulatory barriers in the region are limited, and much work is still needed to improve the status of cancer pain management in the region. Enacting necessary change will require recognition of the unique needs and resources of each country and collaboration across interdisciplinary professional teams to improve cancer pain care in this region.


Pork quality, processing, and sensory characteristics of dry-cured hams as influenced by Duroc crossing and sex.
This study was designed to evaluate Duroc (DU) crossing for Carso dry-cured ham production. One hundred fifty-four pigs (81 females and 73 castrates) of four different genotypes, pure Landrace pigs (LAN), offspring of LAN females crossed with Large White (LW) males (LWxLAN), offspring of LAN females crossed with DU males (DUxLAN), and offspring of LWxLAN females crossed with DU males (DUx[LWxLAN]), were chosen in the weight range of 105 to 120 kg (112.7 +/- 0.4 kg). Raw material quality was evaluated for ham fatness (intra- and intermuscular and subcutaneous) and meat quality (pH, color, water-holding capacity) of longissimus dorsi, biceps femoris, and semimembranosus muscles. Ham weight losses were recorded at different stages of processing. The biceps femoris and semimembranosus muscles were analyzed for chemical composition before (lipid, moisture, total nitrogen, nonprotein nitrogen) and after (moisture, salt, total nitrogen, nonprotein nitrogen) processing. Chemical and sensory analyses were performed on 96 dry hams (12 castrates and 12 females per genotype). Biceps femoris and semimembranosus muscles were evaluated for color, saltiness, aroma, and texture. Pigs of the four genotypes had similar ham fatness as estimated by subcutaneous fat thickness. Duroc crosses exhibited higher intramuscular fat content, marbling, and intermuscular fat. Crossing with DU resulted in lower weight losses during ham processing. Castrates were fatter and had more intra- and intermuscular fat and lower ham processing weight losses than females. A strong negative relationship between ham fatness and ham processing losses was observed. Chemical and sensory traits of dry ham muscles were little affected by DU crossing. Lower salt content of biceps femoris was found in DU crosses. Dry hams from female pigs had higher total and nonprotein nitrogen, but drier, firmer texture and higher resistance to cutting force compared to dry hams from castrated pigs. Crossing with DU demonstrated some disadvantages (more intermuscular fat, more slice visible fat) and advantages (lower weight loss and salt intake) for the quality of dry-cured ham.


A framework for the evidence-based practice of therapeutic jurisprudence: A legal therapeutic alliance.
This paper provides a theoretical rationale for using the constructs of procedural justice, trust and self-determination as a framework to guide the evidence-based practice of therapeutic jurisprudence (TJ). The overarching purpose of TJ is to provide therapeutic outcomes to all participants in the legal system. This paper proposes that in legal decision-making, running a procedurally just process that generates trust amongst participants and allows the parties to experience self-determination, creates a dynamic akin to the therapeutic alliance, which, in therapy, is a reliable predictor of therapeutic outcomes. The paper argues that when a legal therapeutic alliance forms in a legal decision-making process then positive therapeutic outcomes are possible, and the process can be classified as one that accords with the philosophy of TJ. A subsequent argument is that a therapeutic court can be defined as one that enacts such a process. The paper concludes by explaining how the framework can provide both a guide to courts in designing TJ processes and an assessment framework to analyse legal decision-making processes for their therapeutic value.


Symptoms of delirium among elderly medical inpatients with or without dementia.
This study examined the frequencies of the 10 symptoms of delirium identified in DSM-III-R among patients with delirium (DSM-III-R criteria) who did or did not have dementia. The prevalence of each symptom, the numbers of symptoms, and the combinations of symptoms were determined among 322 elderly medical inpatients classified into one of four groups: delirium and dementia (n=128), delirium only (n=40), dementia only (n=94), or neither (n=60). Symptoms were assessed at the time of diagnosis and independently (by use of a different scale) within 24 hours of diagnosis. Delirium appeared to be phenomenologically similar among patients with and those without dementia, although patients with dementia had more psychomotor agitation at the time of diagnosis and more disorganized thinking and disorientation at the second assessment.


[Review on coronary artery disease - part I: epidemiology, pathophysiology, clinical presentation and work-up].
Coronary artery disease affects thousands of Icelanders and is the most common cause of death in Iceland. In recent years great strides have been taken towards deeper understanding and improved treatment of this common disease, resulting in markedly improved outcomes. This evidence based review article is the first of two on coronary artery diseases. It will discuss the epidemiology and pathogenesis of coronary artery disease but also clinical presentation and diagnostic work-up. The review is aimed at a wide readership of physicians, other health care providers and students of health sciences. Current literature will be reviewed with special focus on recent Icelandic studies.


Outcomes of planned home births attended by certified nurse-midwives in southeastern Pennsylvania, 1983-2008.
In this study, we examined the perinatal outcomes of planned home births over a 25-year period (1983-2008) in a group of primarily Amish women (98%) attended by certified nurse-midwives (CNMs) in southeastern Pennsylvania. This was a retrospective, descriptive analysis of data (N = 1836 births) from several CNM practices. Data were abstracted for 25 items, including demographics, labor, and birth. Initially, 2 investigators abstracted 15 records to compare assessments and standardize definitions. Charts were then divided and abstracted individually by one investigator. Several relationships were examined in 2 by 2 tables using the chi-square procedure for the difference in proportions. Maternal and newborn transfers to the hospital were included in the analysis. Of the women who planned home birth for 1836 pregnancies, 1733 of the births occurred at home. Although more than one-third of the women were of high parity (gravida 5-13), rates of postpartum hemorrhage were low (n = 96, 5.5%). There were no maternal deaths. Nearly half of the maternal transfers to the hospital (n = 103, 5.6%) were for ruptured membranes without labor (n = 25, 1.4%) and/or failure to progress (n = 23, 1.3%). The neonatal hospital admission rate also was low (n = 13, 0.75%). Of the 7 (0.4%) early neonatal deaths, all were attributed to lethal congenital anomalies that are common to this population. This study is the first to describe the outcomes of planned home births in a primarily Amish population cared for by CNMs. It also adds to the literature on planned home births in the United States and supports the findings from previous studies that women who have home births attended by CNMs have safety profiles equal to or better than profiles of women who had hospital births in similar populations.


Low-dose methotrexate-induced acute interstitial pneumonitis: Report of two cases from South India and review of literature.
Methotrexate (MTX) is an antimetabolite used as a disease-modifying agent for various rheumatological conditions. We report two patients who were treated with daily low-dose MTX and developed acute interstitial pneumonitis requiring hospital admission. MTX-induced pneumonitis is a rare life-threatening side effect, high index of clinical suspicion is required, treatment is mainly withdrawal of MTX, supportive therapy, and adjunctive steroids, outcome is good if condition is recognized early, and appropriate treatment is given.


Integration of Switchable DNA-Based Hydrogels with Surfaces by the Hybridization Chain Reaction.
A novel method to assemble acrylamide/acrydite DNA copolymer hydrogels on surfaces, specifically gold-coated surfaces, is introduced. The method involves the synthesis of two different copolymer chains consisting of hairpin A, HA, modified acrylamide copolymer and hairpin B, HB, acrylamide copolymer. In the presence of a nucleic acid promoter monolayer associated with the surface, the hybridization chain reaction between the two hairpin-modified polymer chains is initiated, giving rise to the cross-opening of hairpins HA and HB and the formation of a cross-linked hydrogel on the surface. By the cofunctionalization of the HA- and HB-modified polymer chains with G-rich DNA tethers that include the G-quadruplex subunits, hydrogels of switchable stiffness are generated. In the presence of K(+)-ions, the hydrogel associated with the surface is cooperatively cross-linked by duplex units of HA and HB, and K(+)-ion-stabilized G-quadruplex units, giving rise to a stiff hydrogel. The 18-crown-6-ether-stimulated elimination of the K(+)-ions dissociates the bridging G-quadruplex units, resulting in a hydrogel of reduced stiffness. The duplex/G-quadruplex cooperatively stabilized hydrogel associated with the surface reveals switchable electrocatalytic properties. The incorporation of hemin into the G-quadruplex units electrocatalyzes the reduction of H2O2. The 18-crown-6-ether stimulated dissociation of the hemin/G-quadruplex bridging units leads to a catalytically inactive hydrogel.


[Mechanisms of the toxic action of ammonia on the mucous membrane of the upper respiratory tract (an experimental study)].
The objective of the present experimental investigation was to study peculiarities of the toxic action of ammonia vapours on the respiratory organs. The experiments were carried out on 20 white rats. The animals were placed in a special chamber and exposed to ammonia vapours. The histological examination of different internal organs laid emphasis on the lungs and upper respiratory tract. Changes in blood pH values were measured. It is shown that the severity of inhalation intoxication with ammonia vapours depends on the development of asphyxia as a result of laryngeal oedema and spasm. Ammonia vapours penetrating into the bloodstream cause alkalinization of the blood. The results of the study open up prospects for the development of new approaches to the treatment and prevention of laryngeal oedema, modulation of pH values in the blood and mucous membrane of the respiratory organs.


The anionic barrier system on the mesonephric renal glomerulus of the brown hagfish, Paramyxine atami Dean (Cylostomi).
The distribution of anionic groups of acid mucopolysaccharides on the surface of glomerular constituents of a brown hagfish, Paramyxine atami Dean, has been studied morphologically. The ionized anionic groups of acid mucopolysaccharides were labeled on fixed tissues by staining with cationic cacodylate iron colloid (Fe-Cac) at pH 4.0. The glomerular permeability to cationic and anionic macromolecules was observed morphologically in the kidney of the animal injected with native anionic ferritin (NF) or cationized ferritin (CF) into the dorsal aorta. Histochemical staining of tissues with Fe-Cac (pH 4.0) revealed the ionized anionic groups of acid mucopolysaccharides on both luminal and abluminal surfaces of endothelial cells, within the glomerular basement membrane (GBM), and on the visceral epithelial cell surface facing the urinary space. The CF molecules introduced into the dorsal aorta easily passed through the fenestrae of the capillary endothelial cell layer and the thick fibrillar GBM, reaching the urinary space to be adsorbed to the visceral epithelial cell surface or taken up by these visceral epithelial cells. On the other hand, NF hardly passed through the capillary wall. These results show that the nonosmoregulating mesonephric glomerulus of the brown hagfish has a working anionic barrier system. The function of its glomerulus is compared to that of the mammalian metanephric glomerulus.


Expression and characterization of protein kinase C in isolated rabbit parietal cells.
We investigated the expression, characterization and distribution of protein kinase C (PKC) isozymes in isolated rabbit parietal cells (PC). Cellular extracts of PC were analyzed by Western blot using isozyme-specific antibodies. The Ca2+-independent PKC-epsilon was detected in cytosolic, membrane and cytoskeletal fractions of basal and histamine-stimulated PC, whereas the Ca2+-dependent PKC-alpha was confined to the cytosolic and membrane fractions. Cytosolic and membrane fractions were partially purified by DEAE cellulose column chromatography with elution of increasing NaCl concentration. Eluates of 0.15 M and 0.3 M NaCl PC fractions were identified as PKC-alpha and -epsilon isoforms, respectively. Phorbol 12-myristate 13-acetate (TPA) treatment of PC for 15, 30 and 60 sec decreased significantly cytosolic PKC-alpha and increased membrane-associated PKC-alpha. In contrast to the distribution of PKC-alpha, TPA did not alter membrane or cytosolic level of PKC-epsilon. Comparison of the dose-response curves between TPA-induced hydrogen (H+) secretion, as measured by aminopyrine (AP) uptake, and the membrane-associated PKC-alpha suggests that translocation of PKC-alpha is not involved in the H+ secretory process in PC. Furthermore, a PKC inhibitor, staurosporine, produced a concentration-dependent enhancement of histamine-stimulated H+ secretion. These findings suggest that PKC-alpha plays a negative modulatory role, rather than an obligatory role, in H+ secretion. The localization and distribution of PKC-epsilon into the cytoskeletal fraction of PC also suggests that this isozyme may be involved in the cellular regulation of reversible morphological transformation during stimulation.


Resilience in Mothers of Very-Low-Birth-Weight Infants Hospitalized in the NICU.
To develop the theme of Resilience of mothers of very-low-birth-weight infants in the NICU from a qualitative study on maternal role attainment. Secondary analysis using retrospective interpretation, that is, the further development and refinement of content related to resilience that was identified in the original data. A tertiary NICU in Chicago. Twenty-three English-speaking, predominantly single (74%), minority (Black [57%], Hispanic [17%]), low-income (78%), primiparous (78%) mothers of very-low-birth-weight infants. Narrative analysis and core story creation were used to analyze the data related to resilience. A narrative of each participant's birth and NICU story was constructed and recurring meanings were analyzed. Identified patterns were compared across narratives to create one coherent core story that synthesized themes common to all stories. Participants found meaning in redefining their priorities to become advocates for their infants and to "pick themselves up for their babies" by using resources that actively promoted their mental health. NICU-based breastfeeding peer counselors and bedside nurses helped guide participants through their NICU experiences, provided support so participants could gain confidence and competence, and allowed participants to cope with their long-term psychological distress. Participants demonstrated resilience as they learned to live with what was beyond their control. NICU nurses are ideally positioned to capitalize and expand on mothers' health-promoting strengths, resources, and coping strategies to help them further decrease their NICU-related stress and better integrate mothering behaviors into their lives long after NICU discharge.


Central venous oxygen saturation is not predictive of early complications in cancer patients presenting to the emergency department.
Central venous oxygen saturation (ScvO2) is easily observable in oncology patients with long-term central venous catheters (CVC), and has been studied as a prognostic factor in patients with sepsis. We sought to investigate the association between ScvO2 and early complications in cancer patients presenting to the ED. We prospectively enrolled adult cancer patients with pre-existing CVC who presented to the ED. ScvO2 was measured on their CVC. The outcome was admission to the intensive care unit (ICU) or mortality by day 7. ScvO2 was first studied as a continuous variable (%) with a ROC analysis and as a categorical variable (cut-off at < 70%) with a multivariate analysis. A total of 210 cancer patients were enrolled. At baseline, ScvO2 showed no significant difference between patients who were admitted to the ICU or died before day 7, and patients who did not (67%; IQR 62-68% vs. 71%; IQR 65-78% respectively, P = 0.3). The ROC analysis showed the absence of discrimination accuracy for ScvO2 to predict the outcome (AUC = 0.56). By multivariate analysis, ScvO2 < 70% was not associated with the outcome (OR 1.67; 95% CI 0.64-4.36). Variables that were associated with ICU admission or death by day 7 included a shock-index (heart rate/systolic blood pressure) > 1 and a performance status > 2 (OR 4.76; 95% CI 1.81-12.52 and OR 6.23, 95% CI 2.40-16.17, respectively). This study does not support the use of ScvO2 to risk stratify cancer patients presenting to the ED.


Validation of finite element predictions of cartilage contact pressure in the human hip joint.
Methods to predict contact stresses in the hip can provide an improved understanding of load distribution in the normal and pathologic joint. The objectives of this study were to develop and validate a three-dimensional finite element (FE) model for predicting cartilage contact stresses in the human hip using subject-specific geometry from computed tomography image data, and to assess the sensitivity of model predictions to boundary conditions, cartilage geometry, and cartilage material properties. Loads based on in vivo data were applied to a cadaveric hip joint to simulate walking, descending stairs, and stair-climbing. Contact pressures and areas were measured using pressure sensitive film. CT image data were segmented and discretized into FE meshes of bone and cartilage. FE boundary and loading conditions mimicked the experimental testing. Fair to good qualitative correspondence was obtained between FE predictions and experimental measurements for simulated walking and descending stairs, while excellent agreement was obtained for stair-climbing. Experimental peak pressures, average pressures, and contact areas were 10.0 MPa (limit of film detection), 4.4-5.0 MPa, and 321.9-425.1 mm(2), respectively, while FE-predicted peak pressures, average pressures, and contact areas were 10.8-12.7 MPa, 5.1-6.2 MPa, and 304.2-366.1 mm(2), respectively. Misalignment errors, determined as the difference in root mean squared error before and after alignment of FE results, were less than 10%. Magnitude errors, determined as the residual error following alignment, were approximately 30% but decreased to 10-15% when the regions of highest pressure were compared. Alterations to the cartilage shear modulus, bulk modulus, or thickness resulted in +/-25% change in peak pressures, while changes in average pressures and contact areas were minor (+/-10%). When the pelvis and proximal femur were represented as rigid, there were large changes, but the effect depended on the particular loading scenario. Overall, the subject-specific FE predictions compared favorably with pressure film measurements and were in good agreement with published experimental data. The validated modeling framework provides a foundation for development of patient-specific FE models to investigate the mechanics of normal and pathological hips.


Flavonoids from Acacia pennata and their cyclooxygenase (COX-1 and COX-2) inhibitory activities.
Two new flavonoids quercetin 4'-O-alpha-L-rhamnopyranosyl-3-O-beta-D-allopyranoside (1) and apigenin 6-C-[2''-O-(E)-feruloyl- beta-D-glucopyranosyl]-8-C-beta-glucopyranoside (2), along with the known isorhamnetin 3-O-alpha-L-rhamnopyranoside (3), kaempferol 3-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranoside (4), and isovitexin (5) were isolated from the leaves of Acacia pennata Willd. (Mimosaceae) and tested for their anti-inflammatory activity. Their structures were determined by 1D and 2D NMR and mass spectrometry. They were tested for an inhibitory effect on COX-1 and COX-2, showing 60-90% inhibition at 10(-4) g/mL and 5-14% inhibition at 10(-4) g/mL, respectively.


Alzheimer's disease diagnosis disclosure in Brazil: a survey of specialized physicians' current practice and attitudes.
There is little, though growing, interest in the research area of attitudes held among physicians towards disclosing the diagnosis of dementia and Alzheimer's disease (AD), or the current practice on AD disclosure. This study aimed to investigate the practice and attitudes of specialized physicians towards AD diagnosis disclosure in Brazil. A questionnaire was devised to survey the current practice and attitudes regarding diagnosis disclosure of AD in Brazil and sent to specialized physicians (170 geriatricians, 300 neurologists and 500 psychiatrists) by electronic mail. From 970 potential respondents, 181 physicians who usually attend AD patients returned the questionnaire. There were no significant differences between the three specialties regarding the frequency with which they informed patients of their AD diagnosis (p = 0.17). The results revealed that only 44.8% of the physicians would regularly inform the patient of the diagnosis, although 85.6% of these use clear terminology. Despite their usual practice, 76.8% would want to know their diagnosis if they themselves were affected by AD. Disclosure of AD diagnosis is not common among specialized physicians in Brazil and different factors are involved. In the clinical context, discussion on advantages of diagnosis disclosure can be useful for improving the care of AD patients and their families.


Changes in the structure of nuclei after transfer to oocytes.
Nuclear transfer and the potential for cloning animals have refocused attention on the oocyte. This focus is not limited to the use of the oocyte as a recipient in nuclear transfer procedures, but more broadly in terms of what factors are present in the oocyte that are responsible for establishing the developmental pattern of RNA synthesis and subsequent protein production. Deviations in the pattern of RNA synthesis can result in abortions, as well as abnormalities at birth. This paper will focus on the changes to nuclear structure that result from transfer to the cytoplasm of an oocyte, as well as some of the changes in the patterns of RNA synthesis that have been described.


Neurological complications following extrusion of sodium hypochlorite solution during root canal treatment.
To report the presentation and management of two cases with neurological complications secondary to the extrusion of sodium hypochlorite solution into the facial soft tissues during root canal treatment. The clinical features, with particular emphasis on nerve deficit following inadvertent extrusion of sodium hypochlorite, are discussed and its management highlighted. Early and aggressive treatment is advocated following such incidents in order to reduce potentially serious complications. *Neurological sequelae can follow inadvertent hypochlorite extrusion. *Early recognition may avert a potentially more serious outcome. *Active hospital treatment including intravenous steroids and antibiotics is recommended.


Synthesis of peptides related to the prosegment of mouse submaxillary gland renin precursor: an approach to renin inhibitors.
The complete sequence of the structural gene coding for mouse submaxillary gland renin was recently reported and the amino acid sequence of preprorenin was deduced. This sequence includes a 45-amino acid peptide that corresponds to the prosegment of the renin precursor. To investigate whether peptides related to the renin prosegment are able to inhibit renin activity, we have synthesized four peptides having the following structures: Arg-Ile-Pro-OMe, butyloxycarbonyl(Boc)-Leu-Lys-Lys-Met-Pro-OMe, Boc-Arg-Ile-Pro-Leu-Lys-Lys-Met-Pro-OMe, and Boc-Glu-Arg-Ile-Pro-Leu-Lys-Lys-Met-Pro-OMe (corresponding to amino acids 12-14, 15-19, 12-19, and 11-19, respectively, of the renin prosegment). All four peptides were found to inhibit the activity of pure mouse submaxillary renin on a porcine synthetic tetra-decapeptide in vitro, and the most potent inhibitors exhibited IC50 values in the micromolar range. Enzymatic kinetic studies carried out using peptide 15-19 showed an uncompetitive or a mixed type of inhibition with a Ki value of 2.3 X 10(-6) M at 37 degrees C in 0.5 M citrate/phosphate buffer (pH 6.0).


hsCRP, sICAM-1 and TAFI in hemodialysis patients: linking inflammation and hypofibrinolysis to cardiovascular events.
Growing evidence suggests that inflammation, oxidative stress and hypofibrinolysis may have a pivotal role in the high prevalence of cardiovascular disease (CVD) in chronic kidney disease (CKD) patients. This study aims to investigate the association of these processes with the incidence of CVD in hemodialysis (HD) patients and to examine the modulating effect of oral L-arginine in HD patients having CVD. Blood malondialdehyde (MDA), highly sensitive C-reactive protein (hsCRP), soluble intracellular adhesion molecule-1 (sICAM-1) and thrombin-activatable fibrinolysis inhibitor (TAFI) levels were measured in 12 healthy controls and in 62 CKD patients divided into 15 renal impairment, 21 HD, and 26 HD+CVD. Of the latter, 15 patients received oral L-arginine (15 g/day, 5 g t.i.d.) for 1 month. MDA, hsCRP, sICAM-1 and TAFI were significantly elevated in renal impairment patients. HD and HD+CVD experienced higher levels, but only MDA and TAFI were significantly higher in HD+CVD than HD patients. Only MDA was significantly reduced by 41% after L-arginine intake. This study demonstrates the association of inflammation and hypofibrinolysis with hemodialysis especially in patients with CVD. We found no added therapeutic value for L-arginine at the used dose and duration to ameliorate these cascades of events.


Plasma anti-pneumococcal antibody activity of the IgG class and subclasses in otitis prone children.
Plasma anti-pneumococcal polysaccharide antibody activity (serotypes 3, 6a and 23) was determined in samples from 15 otitis prone children, at 30 months of age, and compared with age matched control children and adults. A recently developed enzyme immunoassay, using IgG subclass specific monoclonal antibodies for analysis of pneumococcal antibody activity of different IgG subclasses was employed. Adult sera always contained the highest antibody concentrations, almost exclusively of the IgG2 subclass. Children, on the other hand, had higher amounts of IgG1, significantly exceeding those of the adults, healthy children having higher IgG1, as well as IgG2 values than otitis prone children. The most significant differences were seen with type 6a, less so with type 23 antibodies. No differences in IgG1 anti-type 3 pneumococcal activity were observed between the children and the adults. These findings support the concept that pneumococcal antibody activity is confined to IgG2 and, in addition, it was found that sera from children contain antibodies of both IgG1 and IgG2 subclasses.


Reduced-Size Integer Linear Programming Models for String Selection Problems: Application to the Farthest String Problem.
We present integer programming models for some variants of the farthest string problem. The number of variables and constraints is substantially less than that of the integer linear programming models known in the literature. Moreover, the solution of the linear programming-relaxation contains only a small proportion of noninteger values, which considerably simplifies the rounding process. Numerical tests have shown excellent results, especially when a small set of long sequences is given.


Bone marrow metastasis of glioblastoma multiforme mimicking acute myeloid leukemia.
A 46-year-old female patient with glioblastoma multiforme (GBM), IDH wild type developed severe pancytopenia 5 months after postoperative chemoradiotherapy. Bone marrow aspirate showed normocellular marrow with 70.0% abnormal cells, which suggested the possibility of acute myeloid leukemia. Immunophenotypic analysis did not show any hematological lineage markers, except for cluster of differentiation 56. The results of immunohistochemical staining of glial fibrillary acidic protein and oligodendrocyte transcription Factor 2 were positive. Based on these findings, the patient was diagnosed with bone marrow metastasis from GBM. Bone marrow metastasis from GBM is rare and little is known about the morphological characteristics of bone marrow aspiration smear findings. We experienced a rare case with marrow metastasis from GBM mimicking acute myeloid leukemia.


Regular consumption of both vitamin D- and calcium- and vitamin D-fortified yogurt drink is equally accompanied by lowered blood lipoprotein (a) and elevated apoprotein A1 in subjects with type 2 diabetes: a randomized clinical trial.
Cardiovascular disease (CVD) is the major morbidity and cause of death in diabetic subjects. Observational studies have shown the association of low vitamin D status with poor glycemic control, atherogenic lipid profile, and CVD. However, the possible link between circulating 25-hydroxycholecalciferol and apoproteins (Apo A1 and B) and the atherogenic lipoprotein (a) [Lp(a)] has not been documented to date. Ninety subjects with type 2 diabetes (T2D) aged 30-60 years from both sexes were randomly allocated to one of the 3 groups to receive 2 bottles a day of either (1) plain doogh (PD; containing 150 mg calcium and no detectable vitamin D/250 mL); (2) vitamin D-fortified doogh (DD; containing 150 mg calcium and 500 IU vitamin D/250 mL); or (3) calcium- and vitamin D-fortified doogh (CDD; containing 250 mg calcium and 500 IU vitamin D/250 mL) for 12 weeks. Anthropometric, dietary, and laboratory assessments, including Apo A1, Apo B, and Lp(a), were done. Improvement of vitamin D status in DD and CDD groups, compared to PD, resulted in a significant increase in Apo A1 (mean changes 0.22 ± 0.38, 0.20 ± 0.27 and 0.01 ± 0.35 g/L, respectively, p = 0.047) and a significant decrease in serum Lp(a) (mean changes -0.08 ± 0.30, -0.08 ± 0.31, and 0.14 ± 0.25 μmol/L, respectively, p = 0.011). There was no significant difference between DD and CDD groups. Serum Apo B did not change significantly in any of the groups. Significant amelioration of serum Apo A1 and Lp(a) following improvement of vitamin D status in T2D subjects may have preventive implications against long-term diabetic complications, notably CVD. This trial was registered at ClinicalTrials.gov as NTC01229891.


Effects of estradiol on in vitro nucleoside incorporation and methylation of rat uterine ribonucleic acid.
The in vitro nucleoside incorporation and methylation of uterine RNA was examined by incubating immature rat uteri with either 3H-uridine, 3H-uridine-3H-cytidine, and/or 14C-methyl-methionine. Radioactivity was determined in extracted RNA which was fractionated by gel electrophoresis or by differential solubility in zine acetate or lithium chloride. Estradiol (E2)-treated uteri respond by showing a maximum in vitro incorporation of nucleosides into total RNA and high M.W. RNA within one hr of in vivo treatment. Nucleoside incorporation into low M.W. RNA increased gradually throughout the first 3 hrs of a 4-hr hormone treatment period. E2 in vivo also caused increased in vitro methylation of total, high, and low M.W. uterine RNA fractions. Methylation of all fractions increased through the first 3 hrs of hormone treatment, but greater methylation of low M.W. RNA was apparent. The data indicate that in vivo E2 treatment stimulates an initial transitory stage of in vitro nucleoside incorporation into uterine RNA followed by a more prolonged interval of RNA methylation.


Multidisciplinary management of a fused tooth: a case report.
Objective. Fusion is a dental anomaly that arises through the union of two adjacent teeth. The case report presents multidisciplinary management of a fused maxillary anterior tooth. Case Report. A 10-year-old boy was referred to the pediatric dental clinic with the chief complaint of a large upper anterior tooth. Intraoral and radiographic examinations indicated fusion between the permanent maxillary right central incisor and a supernumerary tooth. According to the treatment plan, the fused tooth was sectioned, and the mesial portion was removed. The remaining tooth section was restored with composite resin, and the diastema between the central incisors was closed with orthodontic treatment. After an 18-month followup period, the tooth showed no sign of pathosis. Conclusion. The technique described here offers a simple and effective method for restoring a fused tooth that reestablishes function, shape, and esthetics.


Field-effect bulk mobilities in polymer semiconductor films measured by sourcemeters.
Semiconducting polymers inherently exhibit polydispersity in terms of molecular structure and microscopic morphology, which often results in a broad distribution of energy levels for localized electronic states. Therefore, the bulk charge mobility strongly depends on the free charge density. In this study, we propose a method to measure the charge-density-dependent bulk mobility of conjugated polymer films with widely spread localized states using a conventional field-effect transistor configuration. The gate-induced variation of bulk charge density typically ranges within ±1018 cm-3; however, this range depends significantly on the energetic dispersion width of localized states. The field-effect bulk mobility and field-effect mobility near the semiconductor-dielectric interface along with their dependence on charge density can be simultaneously extracted from the transistor characteristics using various gate voltage ranges.