Descemet stripping automated endothelial keratoplasty in pediatric age group.
To report the outcomes of DSAEK surgery performed in pediatric patients. Noncomparative interventional case series. All pediatric patients (age up to 16 years) undergoing Descemet automated stripping endothelial keratoplasty (DSAEK) at our Institution since January 2008 have been enrolled in a prospective study. A standard DSAEK, involving delivery of an 8.5-9.5 mm graft by Busin glide, was performed under general anesthesia in 19 eyes of 11 pediatric patients (congenital hereditary endothelial dystrophy n = 13; congenital glaucoma n = 2; posterior polymorphous dystrophy n = 2, and failed penetrating keratoplasty n = 2). Slit-lamp examination, refraction and visual acuity as well as endothelial cell density were evaluated preoperatively as well as 1, 3, 6, 12, and 18 months postoperatively. All surgical procedures were uneventful. Graft detachment occurred in 4 cases and was managed successfully with repeat air injection. All corneas cleared within a week from surgery. Follow-up was 3-18 months. At last follow-up examination, best-corrected visual acuity (BCVA) was better than 20/40 in 8 of the 13 cases of patients old enough to assess vision. A graft rejection episode was seen in 1 case within 3 months from surgery but was reverted with steroidal treatment. No graft failures were observed. DSAEK is an appropriate surgical intervention for children with corneal endothelial failure. In contrast to penetrating keratoplasty (PK), DSAEK is performed under "closed system" conditions, thus minimizing intraoperative risks. Finally, healing is much faster than with PK and all sutures can be removed within 2-4 weeks from surgery, thus allowing fast visual recovery and prompt starting of amblyopia treatment.


Meningoencephalitis secondary to otitis in a gorilla.
An adult female gorilla died following a 13-day illness and was necropsied. Gross and microscopic findings included a 2-cm straw deep in the external auditory meatus, suppurative otitis media and interna, and suppurative meningoencephalitis. Proteus mirabilis was cultured from the internal acoustic pore.


[Complex chronic care situations and socio-health coordination].
Patient-centered healthcare is currently one of the most pursued goals in health services. It is necessary to ensure a sufficient level of cooperative and coordinated work between different providers and settings, including family and social and community resources. Clinical integration occurs when the care provided by health professionals and providers is integrated into a single coherent process through different professions using shared guidelines and protocols. Such coordination can be developed at three levels: macro, which involves the integration of one or more of the three basic elements that support health care (the health plan, primary care and specialty care), with the aim of reducing fragmentation of care; meso, where health and social services are coordinated to provide comprehensive care to elderly and chronic patients; and micro, aimed to improve coordination in individual patients and caregivers. The implementation of new roles, such as Advanced Practice Nursing, along with improvements in family physicians' problem-solving capacity in certain processes, or modifying the place of provision of certain services are key to ensure services adapted to the requirements of chronic patients.


The relationship between Th1/Th2 balance and 1α,25-dihydroxyvitamin D₃ in patients with nasal polyposis.
We aimed to study Th1/Th2 cell balance by measuring the levels of cytokines IL-4, IL-10, and IFN-γ, which play an important role in the immune response of patients with allergic rhinitis and/or nasal polyps, and determine the correlation between Th1/Th2 cell balance and 1α,25-dihydroxyvitamin D(3), an active metabolite of vitamin D. The study subjects were 60 adult patients and 40 healthy volunteers. Subjects were separated into three groups: 30 patients diagnosed with nasal polyposis together with allergic rhinitis formed Group I, 30 patients with nasal polyposis but without allergic rhinitis constituted Group II, and 40 healthy volunteers without nasal polyp and/or allergic rhinitis were the control group, or Group III. IFN-γ, IL-4, IL-10, and total IgE levels were determined in the serum samples of all patients and vitamin D(3) in their plasma. A statistically significant difference was found between the Group I and the control group in their IgE, IL-4, IL-10, IFN-γ, and vitamin D levels (p < 0.05), while there were no such significant differences between Group II and the control group in these measurements (p > 0.05). Within Group I, vitamin D levels showed a negative correlation with IgE and IL-4 levels, and a positive correlation with IFN-γ (p < 0.05). Within Group II, IgE levels showed a positive correlation with IL-4 and IL-10 levels (p < 0.05) and a negative correlation with IFN-γ levels (p < 0.05). In this study, no significant relation was detected between vitamin D deficiency and nasal polyposis in the absence of allergic rhinitis. The study demonstrates that vitamin D is effective on Th1/Th2 balance in patients with allergic rhinitis and that there is a significant relation between vitamin D deficiency and allergy. These results are compatible with the possibility of an important role of vitamin D in the pathogenesis and degree of severity of allergic disease, and its capacity to control allergic disease.


A systematic review and meta-analysis of facial emotion recognition in autism spectrum disorder: The specificity of deficits and the role of task characteristics.
This review assessed the specificity of facial emotion recognition impairment and the role of task characteristics in facial emotion recognition in autism spectrum disorder (ASD). Based on subsets of 148 studies identified in PubMed and PsycINFO, random-effects meta-analyses showed significant impairment in recognizing all basic facial emotions in ASD. Additionally, ASD involves poorer facial emotion recognition than other clinical conditions and has similar impairment in recognizing emotional and nonemotional facial attributes, as well as in recognizing emotion in faces and other modalities. Furthermore, there are significant moderating effects for emotion complexity and holistic processing, a statistical trend for task type, and no significant effect for motion, social relevance, or stimulus salience on facial emotion recognition in ASD. Altogether, this review suggests nonselective facial emotion recognition impairment in ASD. Such impairment is relatively specific to ASD but is not specific to the recognition of emotional facial attributes or emotion recognition in the face modality. Identifying the role of task characteristics improves our understanding of the mechanisms underlying facial emotion recognition in ASD.


'Gd(-) Hôtel Dieu': a new G-6PD variant with chronic hemolysis in a Negro patient from Senegal.
A G-6PD deficiency was detected in a Negro patient from Senegal suffering from congenital nonspherocytic hemolytic anemia. The main characteristics of this variant were: profound defect of G-6PD activity in the red cells, decreased immunologic specific activity, fast electrophoretic mobility, decreased Km-G-6P and normal Km-NADP+, normal inhibition by ATP and NADPH, slightly increased utilization of the substrate analogues, slightly biphasic pH curve, high heat lability, subnormal activation energy. The characteristics of this variant being unique, it was called 'G-6PD Hôtel Dieu.'


The direct involvement of cAMP-dependent protein kinase in the regulation of collagen synthesis by parathyroid hormone (PTH) and PTH-related peptide in osteoblast-like osteosarcoma cells (UMR-106).
The present study was performed to characterize the direct involvement of cAMP-dependent protein kinase (PKA) in the regulation of collagen synthesis by parathyroid hormone (PTH) and PTH-related peptide (PTHrP) in osteoblastic osteosarcoma cells, UMR-106. Sp-cAMPS (10(-4)M), a direct activator of PKA, as well as dibutyryl cAMP (dbcAMP, 10(-4)M) significantly inhibited collagen synthesis. Human (h) PTH-(1-34) (10(-7)M) and hPTHrP (10(-7) M) inhibited collagen synthesis to the same degree. Although Rp-cAMPS, which acted directly as an antagonist in the activation of PKA, did not affect collagen synthesis by itself, it significantly antagonized dbcAMP- and Sp-cAMPS-induced inhibition of collagen synthesis. Moreover, Rp-cAMPS antagonized PTH- and PTHrP-induced inhibition of collagen synthesis to the same degree. The present study first indicated that the activation of PKA was directly linked to the regulation of collagen synthesis by PTH in osteoblast and that PTHrP had the same effect on collagen synthesis presumably through the same mechanism as PTH.


The impact of a brief motivational intervention on unprotected sex and sex while high among drug-positive emergency department patients who receive STI/HIV VC/T and drug treatment referral as standard of care.
This randomized, controlled trial, conducted among out-of-treatment heroin/cocaine users at an emergency department visit, tests the impact on sexual risk of adding brief motivational intervention (B-MI) to point-of-service testing, counseling and drug treatment referral. 1,030 enrollees aged 18-54 received either voluntary counseling/testing (VC/T) with drug treatment referral, or VC/T, referral, and B-MI, delivered by an outreach worker. We measured number and proportion of non-protected sex acts (last 30 days) at 6 and 12 months (n = 802). At baseline, 70% of past-30-days sex acts were non-protected; 35% of sex acts occurred while high; 64% of sexual acts involved main, 24% casual and 12% transactional sex partners; 1.7% tested positive for an STI, and 8.8% for HIV. At six or 12 month follow-up, 20 enrollees tested positive for Chlamydia and/or Gonorrhea, and 6 enrollees HIV sero-converted. Self-reported high-risk behaviors declined in both groups with no significant between-group differences in behaviors or STI/HIV incidence.


A quantitative assessment of the effect of medium composition on mouse myogenesis in vitro.
The effect of variations in medium horse serum (HS) and chick embryo extract on the extent of myogenesis in primary mouse muscle cultures was investigated. Seeding efficiency at 24 h in culture did not vary with medium composition, but total cell number at 8 days was diminished at low embryo extract concentrations. Five media from the range of 16 tested, supported significantly greater myogenesis. Within this group of 5, there was no difference in ability to support myogenesis. The effect of medium composition on myogenesis is discussed.


YKL-40 levels in the cerebrospinal fluid and serum of patients with aneurysmal subarachnoid hemorrhage: preliminary results.
YKL-40 is a newly discovered matrix protein thought to be secreted during the acute stages of inflammation. Clinical studies have revealed that YKL-40 has growth factor and potent migration factor activity for cells involved in inflammation and tissue remodeling processes. It has recently been speculated that YKL-40 may serve as a specific serologic marker of neutrophil function at the site of acute tissue inflammation. We aimed to quantify the levels of YKL-40 in both cerebrospinal fluid and serum of ten consecutive patients with aneurysmal subarachnoid hemorrhage and to speculate on the origin of this glycoprotein. The levels were also compared with ten control patients with hydrocephalus. We found that patients with aneurysmal subarachnoid hemorrhage had significantly higher YKL-40 levels in both cerebrospinal fluid and serum than controls. The authors believe that YKL-40 is expressed in cerebrospinal fluid due to stress on neural structures while a damaged blood-brain barrier allows entry of neutrophils and macrophages from the systemic circulation.


Factors associated with internal rotation outcomes after reverse shoulder arthroplasty.
Reverse shoulder arthroplasty (RSA) was introduced in 1985 by Grammont for patients with gleno-humeral osteoarthritis and severe rotator cuff damage. Internal rotation (IR) is limited in some patients after RSA. The objective of this study was to identify pre- and intra-operative factors associated with good IR outcomes 6 months after RSA. The condition of the residual cuff (usually the sub-scapularis and teres minor) and inferior glenosphere overhang are the main factors associated with IR outcomes after RSA. A total of 36 patients who underwent RSA between 2 November 2015 and 10 January 2017 were enrolled prospectively. The inclusion criterion was massive rotator cuff tear with or without osteoarthritis and gleno-humeral osteoarthritis with asymmetrical glenoid wear. The pre-operative work-up included determination of the Constant score, Subjective Shoulder Value (SSV), and passive and active motion ranges; standard radiographs; and computed tomography. The same clinical and radiological parameters were recorded in all patients during a visit 6 months after surgery. After surgery, all motion ranges were improved except IR with the elbow by the side (IR1, ability to place the hand on the back). IR1 to or above L3 was significantly associated with a lower body mass index (p=0.04), good passive IR before surgery (p=0.056), a smaller pre-operative glenoid inclination angle, and greater glenosphere overhang (p=0.03). Neither the condition of the sub-scapularis nor sub-scapularis repair were significantly associated with post-operative IR1. IR1 was significantly more limited in patients whose teres minor was normal. Satisfactory active IR1 correlated with good passive IR1. IR1 was better in thin individuals who had non-concentric gleno-humeral osteoarthritis. Inferior glenosphere overhang of 6mm or more was associated with a greater range of IR. IV, prospective observational cohort study.


Left pleural effusion after coronary artery bypass decreases with a supplemental pleural drain.
This prospective study was undertaken to determine the incidence of symptomatic left pleural effusion after coronary artery bypass grafting, and to determine if routine drainage of the pleural cavity with a supplemental flexible drain reduces this incidence. The clinical course of study patients was prospectively recorded during the initial hospitalization and at 6-weeks after surgery. All patients had a mediastinal and a left pleural tube, which were removed on the 1st postoperative day. The supplemental drain system was implanted in a subset of patients and remained in place for 3 to 5 days. A symptomatic effusion was defined as one that required thoracentesis, tube thoracostomy, or readmission for treatment. A total of 460 patients were studied, of whom 115 had a supplemental drain. The two groups (supplemental drain versus control) were equivalent with respect to age, gender distribution, and comorbid diseases. The incidence of symptomatic left pleural effusion for the entire group was 9.8% (45 of 460). Symptomatic left pleural effusion occurred in 11.9% (41 of 345) patients when only chest tubes were used, and in 3.5% (4 of 115) when a supplemental drain was placed. This difference was significant (F ratio 7.583, p < 0.005). There were no complications from the supplemental drain. The incidence of symptomatic left pleural effusion can be greatly reduced with the use of a supplemental pleural drain that remains in place for several days after surgery.


Alpha-1-antitrypsin: frequencies of PiM subtypes and serum concentration in the Japanese population.
PiM subtypes were determined by isoelectric focusing of the sera of 746 Japanese at the age of 16-60 years. The gene frequencies were calculated: PiM1 = 0.7855, PiM2 = 0.1528 and PiM3 = 0.0617. The serum concentration of alpha-1-antitrypsin was measured by laser-nephelometric immunoassay of the sera of 284 individuals. A statistically significant difference (p less than 0.01) in the serum concentration was found between M1 (2.63 +/- 0.67 g/l) and M1M2 (2.39 +/- 0.59 g/l).


Lujan-Fryns syndrome (X-linked mental retardation with marfanoid habitus): report of three cases and review.
We report on three further cases of mildly retarded patients with marfanoid habitus and a pattern of minor anomalies. These patients are likely to be affected with the Lujan-Fryns syndrome. We have reviewed twenty cases from the literature for a better delineation of this newly recognized disorder.


Prospective randomized, double-blinded, placebo-controlled trial of preoperative rofecoxib for pain relief in uterine curettage.
To evaluate the analgesic efficacy of preoperative rofecoxib in patients who underwent uterine curettage. This double-blinded, randomized, placebo-controlled trial included 80 women who underwent uterine curettage. Forty women were randomly assigned to rofecoxib 50 mg and 40 women to the placebo. The main outcome measure was the intensity of pain measured by the visual analog scale and categorical pain scores during and after the procedure. Chi-squared, Fisher exact, Student t test, and Mann-Whitney U tests were used for statistical analysis. The intensity of pain was not found to be different between groups over the course of procedure (P>0.05). There were no serious adverse effects in this study. The preoperative administration of rofecoxib was not effective in reducing pain in uterine curettage.


Involvement of an acidic protein in regulation of smooth muscle contraction by the tropomyosin-leiotonin system.
An acidic Ca-binding protein of about 18,000 dalton, different from both modulator protein and troponin C, was found to be involved in the regulatory mechanism of smooth muscle contraction by the tropomyosin-leiotonin system.


Brain concentrations of mGluR5 negative allosteric modulator MTEP in relation to receptor occupancy--Comparison to MPEP.
To verify relation between brain free levels, receptor occupancy in vivo and in vitro affinity at the target for mGluR5 negative allosteric modulator (NAM) MTEP. We evaluated plasma and brain extra-cellular fluid (ECF) concentration of MTEP at behaviourally active dose (5mg/kg) using in vivo microdialysis. These values were compared it to the affinity in vitro (receptor binding and FLIPR) and to receptor occupancy in vivo. Another, related substance, MPEP was used for comparison. MTEP and MPEP respectively inhibited mGluR5 receptors function in vitro with an affinity of 25.4 and 12.3 nM respectively. Accordingly peak ECF (extracellular fluid) levels were 1.3 and 0.14 μM, and peak total plasma levels were 7-11 and 2.6 μM. The ED50 for in vivo receptor occupancy was for both agents in the range of 0.8-0.7 mg/kg. At behaviourally active dose MTEP produced complete mGluR5 receptor occupancy but over 50 times higher ECF concentrations than affinity for mGluR5 receptor in vitro. This difference is seems lower for other mGluR5 NAM compounds such as MPEP. A possibly explanation could be different distribution in body compartments of both agents leading to errors of estimation with the microdialysis technique or different pharmacological activity at the receptor.


Subconjunctival dislocation of intraocular lens implant.
Eight weeks after intracapsular cataract extraction with implantation of a Binkhorst iris-clip lens joined with a suture to a peripheral iridectomy at the 12 o'clock position, a 52-year-old woman struck the right side of her head. The corneoscleral wound ruptured for three fourths of its length and the artificial lens was located in the subconjunctiva in the superior-nasal quadrant of the eye. The lens was removed, the iris reposited, and the anterior chamber reformed, and the wound resutured. Her vision was 6/12 (20/40) at the time of discharge.


Neurodevelopmental performance among school age children in rural Guatemala is associated with prenatal and postnatal exposure to carbon monoxide, a marker for exposure to woodsmoke.
We investigated whether early life chronic exposure to woodsmoke, using personal passive 48-h carbon monoxide (CO) as an indicator, is associated with children's neurodevelopmental and behavioral performance. CO measures were collected every 3 months from 2002 to 2005 among mother-child dyads during the Randomized Exposure Study of Pollution Indoors and Respiratory Effects (RESPIRE) stove intervention trial in San Marcos, Guatemala. From March to June, 2010, study children of age 6-7 years, performed a follow-up non-verbal, culturally adapted neurodevelopmental assessment. We found inverse associations between CO exposure of pregnant mothers during their 3rd trimesters (m=3.8ppm ± 3.0ppm; range: 0.6-12.5 ppm) and child neuropsychological performance. Scores on 4 out of 11 neuropsychological tests were significantly associated with mothers' 3rd trimester CO exposures, including visuo-spatial integration (p<0.05), short-term memory recall (p<0.05), long-term memory recall (p<0.05), and fine motor performance (p<0.01) measured using the Bender Gestalt-II's Copy, Immediate Recall, and an adapted version of a Delayed Recall Figures drawing, and the Reitan-Indiana's Finger Tapping Tests, respectively. These 4 significant finding persisted with adjustment for child sex, age, visual acuity, and household assets (socio-economic status). Summary performance scores were also significantly associated with maternal 3rd trimester CO when adjusted for these covariates. Other variables accounting for variance but were excluded in our final multiple regression models included the following: HOME environment stimulation score, child examiner, WHO height-for-age percentile, and age that the infant stopped breastfeeding. This seems to be the first study on woodsmoke exposure and neurodevelopment, and the first longitudinal birth cohort study on chronic early life CO exposures, determined by high quality measures of mothers' and infants' personal CO exposures, and using well-established, reliable child neuropsychological tests. Further research is needed to replicate our results and inform future interventions and air quality standards for woodsmoke and CO.


The importance of accounting for testing and positivity in surveillance by time and place: an illustration from HIV surveillance in Japan.
The number of tests performed is an important surveillance indicator. We illustrate this point using HIV surveillance data, focusing on Tokyo and Okinawa, two prefectures with high HIV notification rates in Japan. Restricting to data reported from local public health centres and affiliate centres where testing data are accessible, we assessed HIV surveillance data during 2007-2014, based on the annual HIV notification rate (per 100 000 population), HIV testing rate (per 100 000 population) and proportion testing HIV-positive (positivity). Nationally, testing activity and positivity showed an inverse relationship; in 2008, the testing rate peaked, but positivity was lowest. While notification rates were higher for Tokyo (median = 0.98, range = 0.89-1.33) than Okinawa (median = 0.61, range = 0.42-1.09), Okinawa had slightly higher testing rates (median = 187, range = 158-274) relative to Tokyo (median = 172, range = 163-210). Positivity was substantially lower in Okinawa (median = 0.34%, range = 0.24-0.45%) compared with Tokyo (median = 0.57%, range = 0.46-0.67%). Relative to the national testing rate (median = 85, range = 80-115) and positivity (median = 0.34%, range = 0.28-0.36%), Tokyo had higher positivity, despite more testing. In 2014 in Okinawa, all three indicators increased, providing a strong reason to be concerned as positivity increased despite more testing. Together with other information, accounting for testing and positivity improve interpretation of surveillance data to guide public health assessments.


Catechol-O-methyltransferase (COMT) genotypes and working memory: associations with differing cognitive operations.
Catechol-O-methyltransferase (COMT) is a strong candidate gene for schizophrenia and cognitive functions disrupted in this disorder. This report examines the relation of COMT genotypes to performance on a battery of working memory tests differing in the cognitive operations to be performed on the material. A large sample of 402 healthy adults were tested on four working memory tests: Spatial Delayed Response (SDR), Word Serial Position Test (WSPT), N-back, and Letter-Number Sequencing. A subsample (n = 246) was tested on the Wisconsin Card Sorting Test (WCST). A saliva swab was used to obtain DNA from all participants. Letter-Number Sequencing, which requires both storage and manipulation of information, was the only working memory test that showed expected differences among COMT genotypes, with the met/met group showing the best performance and the val/val group the poorest performance. As in previous studies, the met/met group also performed better than the val/val group on the WCST. COMT genotypes were not associated with performance on tests measuring simple storage, maintenance of temporal order or updating of information in working memory. Genotype differences in Letter-Number Sequencing and WCST suggest that higher-order components of processing (e.g., mental manipulation) are more closely related to this gene.


Ultrasmall Au nanoparticles modified 2D metalloporphyrinic metal-organic framework nanosheets with high peroxidase-like activity for colorimetric detection of organophosphorus pesticides.
Ultrasmall Au nanoparticles (UsAuNPs) in the size range of 4.0-7.0 nm was successfully immobilized on the surface of 2D metalloporphyrinic metal-organic framework nanosheets (2D MOF). Firstly, The obtained hybrid nanomaterial, UsAuNPs/2D MOF, was fully characterized by TEM, HRTEM, element mapping images and XPS. Then, the peroxidase-like activity of UsAuNPs/2D MOF was comparatively studied with other hybrid nanozyme to explore the influence of AuNPs size on peroxidase-like activity. Further, UsAuNPs/2D MOF with outstanding peroxidase-like activity was selected to form ternary cascade enzyme reaction with acetylcholinesterase (AChE) and choline oxidase (ChOx). Based on the inhibitory effect of organophosphorus pesticides on AChE, a fast and sensitive colorimetric method was established for trichlorfon detection with the advantages of simple operation, low detection limit (1.7 μM), good linear range (1.7-42.4 μM) and high accuracy (recovery rate of 96.6-105.3%). Finally, this method was applied to visual analysis of trichlorfon concentration in tomatoes, cucumbers and eggplants.


The pore domain in glutamate-gated ion channels: Structure, drug binding and similarity with potassium channels.
Ionotropic glutamate receptors in the CNS excitatory synapses of vertebrates are involved in numerous physiological and pathological processes. Decades of intensive studies greatly advanced our understanding of molecular organization of these transmembrane proteins. Here we focus on the channel pore domain, its selectivity filter and the activation gate, and the pore block by organic ligands. We compare findings from indirect experimental approaches, including site-directed mutagenesis, with recent crystal and cryo-EM structures of different channels in different functional states and complexed with different ligands. We summarize remaining uncertainties and unresolved problems related to the channel structure, function and pharmacology.


Preventive health care among older women in an academic primary care practice.
We sought to examine the use of preventive health services among older women and to assess how age and illness burden influence care patterns. The charts of 299 women aged > or =80 and 229 women aged 65-79 years who did not have dementia or terminal illness at 1 academic primary care practice in Boston were reviewed between July and December 2005 to determine receipt of screening tests (e.g., mammography), counseling on healthy lifestyle (e.g., exercise), and/or geriatric health issues (e.g., incontinence), and immunizations. Illness burden was quantified using the Charlson Comorbidity Index (CCI). Women aged > or =80 were more likely than women aged 65-79 to have a CCI of > or =3 (24.0% vs. 16.7%) and were less likely to receive all screening tests. However, receipt of mammography (47.8%) and colon cancer screening (51.2%) was still common among women aged > or =80 and was not targeted to older women in good health. Women aged > or =80 were less likely to be screened for depression (adjusted relative risk [aRR] 0.6; 95% confidence interval [CI], 0.5-0.8), osteoporosis (aRR, 0.6; 95% CI, 0.5-0.9), or counseled about exercise (aRR 0.8; 95% CI, 0.6-0.9) than younger women, but were more likely to receive counseling about falls (aRR 1.9; 95% CI, 1.4-2.6) and/or incontinence (aRR 1.8; 95% CI, 1.2-2.6). However notes documenting discussions about mood (28.6%), exercise (40.0%), falls (28.8%), or incontinence (20.8%) were low among all women. In a comprehensive review of preventive health measures for elderly women, many in poor health were screened for cancer. Meanwhile, many older women were not screened for depression or counseled about exercise, falls, or incontinence. There is a need to improve delivery of preventive health care to older women.


Delayed graft rejection in autoimmune islet transplantation via biomaterial immunotherapy.
The induction of operational immune tolerance is a major goal in beta-cell replacement strategies for the treatment of type 1 diabetes. Our group previously reported long-term efficacy via biomaterial-mediated programmed death ligand 1 (PD-L1) immunotherapy in islet allografts in nonautoimmune models. In this study, we evaluated autoimmune recurrence and allograft rejection during islet transplantation in spontaneous nonobese diabetic (NOD) mice. Graft survival and metabolic function were significantly prolonged over 60 days in recipients of syngeneic islets receiving the biomaterial-delivered immunotherapy, but not in control animals. The biomaterial-mediated PD-L1 immunotherapy resulted in delayed allograft rejection in diabetic NOD mice compared with controls. Discrimination between responders and nonresponders was attributed to the enriched presence of CD206+ program death 1+ macrophages and exhausted signatures in the cytotoxic T cell compartment in the local graft microenvironment. Notably, draining lymph nodes had similar remodeling in innate and adaptive immune cell populations. This work establishes that our biomaterial platform for PD-L1 delivery can modulate immune responses to transplanted islets in diabetic NOD mice and, thus, can provide a platform for the development of immunologic strategies to curb the allo- and autoimmune processes in beta-cell transplant recipients.


Intra-hippocampal transplantation of neural precursor cells with transgenic over-expression of IL-1 receptor antagonist rescues memory and neurogenesis impairments in an Alzheimer's disease model.
Ample evidence implicates neuroinflammatory processes in the etiology and progression of Alzheimer's disease (AD). To assess the specific role of the pro-inflammatory cytokine interleukin-1 (IL-1) in AD we examined the effects of intra-hippocampal transplantation of neural precursor cells (NPCs) with transgenic over-expression of IL-1 receptor antagonist (IL-1raTG) on memory functioning and neurogenesis in a murine model of AD (Tg2576 mice). WT NPCs- or sham-transplanted Tg2576 mice, as well as naive Tg2576 and WT mice served as controls. To assess the net effect of IL-1 blockade (not in the context of NPCs transplantation), we also examined the effects of chronic (4 weeks) intra-cerebroventricular (i.c.v.) administration of IL-1ra. We report that 12-month-old Tg2576 mice exhibited increased mRNA expression of hippocampal IL-1β, along with severe disturbances in hippocampal-dependent contextual and spatial memory as well as in neurogenesis. Transplantation of IL-1raTG NPCs 1 month before the neurobehavioral testing completely rescued these disturbances and significantly increased the number of endogenous hippocampal cells expressing the plasticity-related molecule BDNF. Similar, but less-robust effects were also produced by transplantation of WT NPCs and by i.c.v. IL-1ra administration. NPCs transplantation produced alterations in hippocampal plaque formation and microglial status, which were not clearly correlated with the cognitive effects of this procedure. The results indicate that elevated levels of hippocampal IL-1 are causally related to some AD-associated memory disturbances, and provide the first example for the potential use of genetically manipulated NPCs with anti-inflammatory properties in the treatment of AD.


Peptidomic analysis of digested products of surimi gels with different degrees of cross-linking: In vitro gastrointestinal digestion and absorption.
To investigate the cross-linking degree on the in vitro gastrointestinal digestion and absorption properties of surimi gel, three types of surimi gels with low, moderate, and high cross-linking degrees were prepared, and then in vitro digestion models (static and dynamic) and a Caco-2 cell monolayer model combined with LC-MS/MS were used to do peptidomic analysis of digestive and absorbed juices. The results showed that an increase in cross-linking degree promoted the release of peptides after gastrointestinal digestion. These peptides originated from the myosin head and rod, the rod was the main digestion region. More potential bioactive peptides from intestinal digestive juice could be transported through the intestinal epithelium. Compared with static digestion, dynamic digestion digested surimi gels more thoroughly, especially during gastric digestion. This study provides a theoretical basis and guidance for the production of surimi products with higher nutritional value and the in vitro digestion methods of gelatinous foods.


High-performance size-exclusion chromatography of polypeptides on a TSK G2000SW column in acidic mobile phases.
Polypeptides subjected to high-performance liquid chromatography on a TSK G2000SW column in acidic mobile phases of low ionic strength underwent a combination of size exclusion and ion exclusion from the matrix. The distribution coefficient (Kd) of each polypeptide was dependent upon the concentration of ion-pairing agent present and increased as the concentration of ion-pairing agent increased. The fractionation range of the column could thus be manipulated by altering the concentration of acid in the mobile phase. The nature of the ion-pairing acid, in terms of hydrophilic or hydrophobic ion pairing, also had an effect on the chromatography, such that hydrophobic ion-pairing agents lead to increased Kd values, especially in the case of the most basic polypeptides. To account for these results it is proposed that the TSK GSW matrix is cationic at low pH, and that ion pairing suppresses the ion exclusion experienced by cationic polypeptides under these conditions.


Increasing the pH value during thermal processing suppresses the starch digestion of the resulting starch-protein-lipid complexes.
To date, how the pH conditions of thermal processing tailor the structure and digestibility of resulting starch-based complexes remains largely unclear. Here, indica rice starch (IRS), stearic acid (SA), and a whey protein isolate (WPI) were used as materials. Increasing the pH value from 4 to 8 during thermal processing (pasting) mainly suppressed the starch digestion of starch-WPI-SA complexes rather than starch-SA counterparts. The starch-SA complexes showed moderate structural changes as the pH value rose, and there was less rapidly digestible starch (RDS) only at pH 8. For the starch-WPI-SA complexes, an increased pH value allowed larger nonperiodic structures and more V-type starch crystallites, with almost unchanged short-range orders but apparently collapsed networks at pH 8. Such ternary complexes displayed more resistant starch (RS) as the pH value rose. The ternary sample at pH 8 contained ca. 29.87% of the RS fractions.


Modulation of the Gut Microbiome to Improve Clinical Outcomes in Hepatocellular Carcinoma.
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. Recently, the gut microbiota has been shown to be closely linked to modulation of the immune and inflammatory responses, hence its potential as a therapeutic target. Although still under intense investigation, there exists a 'gut-liver axis' that links changes in the gut to the liver. In this regard, composition of gut microbiota and related metabolites, such as bile acids and short-chain fatty acids, have been shown to orchestrate key immune-metabolic events in liver disease and liver cancer. As hepatic immune cells are important determinants of antitumor responses, it is now increasingly recognized that the gut-liver axis plays a key role in influencing the intrahepatic immune response in HCC to favor a pro- or antitumor immune milieu. Hence, modulation of gut microbiota is potentially an attractive option to reinvigorate the antitumor responses. In this regard, promising evidence from melanoma preclinical and clinical studies has demonstrated the efficacy of gut-based intervention in reinvigorating the antitumor responses and improving responses to immunotherapy. However, the role of gut-based interventions as a therapeutic option in HCC remains to be elucidated. This review details how the gut microbiota and bacterial metabolites affect gut barrier function and ultimately immune response in HCC and raises the question of the potential of gut-based interventions as an adjunct therapy for patients with HCC receiving immunotherapy.


Extraction and pre-concentration of parabens in liquid pharmaceutical samples by dispersive liquid-liquid microextraction based on deep eutectic solvents.
In this paper dispersive liquid-liquid microextraction using deep eutectic solvent (DES), as an extraction solvent, was applied for the pre-concentration and determination of parabens in liquid pharmaceutical samples. A DES composed of a hydrogen bond acceptor [choline chloride (ChCl)] and a hydrogen bond donor (glucose) achieved the highest extraction efficiency. Therefore, this solvent was selected as the extraction solvent. After the synthesis of this solvent, its various properties were investigated. Thermogravimetric analysis, X-ray diffraction, and Fourier transform infrared spectroscopy were used for this purpose and the successful synthesis of the solvent was confirmed. HPLC with photodiode array detection was used for the analysis of paraben species. Parameters affecting the extraction efficiency were monitored and optimized through univariate analysis and experimental design. Under the optimal conditions (pH of aqueous solution 4.5, ethanol as the disperser solvent, and glucose DES as the extraction solvent), the linearity range of 0.1-5000 ng mL-1 was obtained with the coefficient of determination (R2 ) between 0.993 and 0.9962. Limits of detections ranged from 0.04 to 0.15 ng mL-1 , with relative standard deviations from 1.8% to 6.8%. The developed method was applied to the determination of parabens in liquid pharmaceuticals such as ampule, syrups, and nose drop samples. A certain amount of paraben was added to the tested real samples to increase their shelf life. The relative recoveries in these real samples ranged between 80.9% and 103.1%.


Hepatic mensenchymal hamartoma of an infant.
An 8-month-old boy was found to have a solitary hepatic mesenchymal hamartoma. Histologically, the lesion appeared as a large island of loose mesenchymal tissue with few cystic bile ducts and liver cells. Electronmicroscopy showed microvilli on the surface of tumor cells and desmosomes between the cells. Immunohistochemical studies showed that alpha-fetoprotein was localized in the proliferating liver cells and bile ductal epithelium of this neoplasm. This case is the 17th case of hepatic mesenchymal hamartoma reported in Japan.


The King-Devick test of rapid number naming for concussion detection: meta-analysis and systematic review of the literature.
Vision encompasses a large component of the brain's pathways, yet is not represented in current sideline testing. We performed a meta-analysis of published data for a vision-based test of rapid number naming (King-Devick [K-D] test). Pooled and meta-analysis of 15 studies estimated preseason baseline K-D scores and sensitivity/specificity for identifying concussed versus nonconcussed control athletes. Baseline K-D (n = 1419) showed a weighted estimate of 43.8 s (95% CI: 40.2, 47.5; I2 = 0.0%; p=0.85 - indicating very little heterogeneity). Sensitivity was 86% (96/112 concussed athletes had K-D worsening; 95% CI: 78%, 92%); specificity was 90% (181/202 controls had no worsening; 95% CI: 85%, 93%). Rapid number naming adds to sideline assessment and contributes a critical dimension of vision to sports-related concussion testing.


Central venous oxygen saturation is a good indicator of altered oxygen balance in isovolemic anemia.
Red blood cell transfusion is done primarily as a means to improve oxygen delivery (DO₂). Current transfusion guidelines are based solely on hemoglobin levels, regardless of actual DO₂ need. As central venous oxygen saturation (ScvO₂) may reflect imbalances in DO₂ and consumption (VO₂) the aim of this study was to investigate the value of ScvO₂ as an indicator of oxygen balance in isovolemic anemia. After splenectomy, anesthetized Vietnamese mini pigs (n = 13, weight range: 18-30 kg) underwent controlled bleeding in five stages (T₀-T₅). During each stage approximately 10% of the estimated starting total blood volume was removed and immediately replaced with an equal volume of colloid. Hemodynamic measurements and blood gas analysis were then performed. Each stage of bleeding resulted in a significant fall in hemoglobin, T₀ : 125 (113-134) to T(5) : 49 (43-55) g/l [T₀ : 7.7 (6.9-8.2) to T₅ : 3.0 (2.6-3.4) mmol/l]. The O₂-extraction (VO₂/DO₂) increased significantly only from T₃ : 35 (21-40) %, P < 0.05. The change of ScvO₂ showed a similar pattern and dropped below the physiological threshold of 70% at T₄ : 68 (61-76) %. At this point, hemoglobin was below the recommended transfusion trigger value, 59 (53-67) g/l [3.6 (3.3-4.1) mmol/l]. There was a strong significant association between ScvO₂< 70%) and VO₂/DO₂ > 30%): r = -0.71, r² = 0.50, P < 0.001. The results of this study show that ScvO₂ reflects changes of VO₂/DO₂ in isovolemic anemia better than Hb alone, therefore it may be used as an additional indicator of blood transfusion in clinical practice.


Intense near-infrared emission of 1.23 μm in erbium-doped low-phonon-energy fluorotellurite glass.
Intense near-infrared emission located at 1.23 μm wavelength originating from the erbium (Er(3+)):(4)S3/2→(4)I11/2 transition is observed in Er(3+)-doped fluorotellurite glasses. This emission is mainly contributed by the relatively low phonon energy of the fluorotellurite glass host (~776 cm(-1)). Judd-Ofelt analysis indicates a strong asymmetry and covalent environment between Er(3+) ions and ligands in the host matrix. The emission cross-section was calculated to be 2.85×10(-21) cm(2) by the Füchtbauer-Ladenburg equation, and the population inversion is realized according to a simplified evaluation. The results suggest that the fluorotellurite glass system could be a promising candidate for the development of optical amplifiers and lasers operating at the relatively unexplored 1.2 μm wavelength region.


Properties of aqueous solutions of hydrophobically modified polyethylene imines in the absence and presence of sodium dodecylsulfate.
Four modified hyperbranched polyethylene imines (PEIs) were synthesized by means of the alkylation of PEI. SAXS, viscosity, surface tension, and pyrene fluorescence emission were then used as techniques to examine the conformation and aggregation of the modified PEIs in aqueous solution, in the absence and presence of sodium dodecylsulfate (SDS). Analysis of the SAXS data showed that the radius of gyration decreases with an increase in the alkyl chain length of the polymer, while the viscosity data indicated a decrease in the intrinsic viscosity under the same conditions. The nonmodified PEI was not surface active, while the hydrophobically modified samples showed pronounced surface activity and the presence of hydrophobic domains. On addition of SDS, the onset of the formation of polymer-surfactant complexes was determined, indicating a decrease in the critical aggregate concentration with an increase in the alkyl chain length of the polymer backbone.


Effects of Vitamin D on Migraine: A Meta-Analysis.
The aim of this study was to evaluate the difference in mean serum 25-hydroxy vitamin D level between migraineurs and nonmigraineurs, the association between hypovitaminosis D and migraine, and the effects of oral vitamin D supplementation on migraine-related symptoms as compared to placebo. Relevant databases were searched for observational studies and randomized-controlled trials (RCTs) which evaluated the difference in mean serum 25-hydroxy vitamin D level between migraineurs and nonmigraineurs; the association between hypovitaminosis D and migraine; and the effects of vitamin D supplementation on migraine-frequency, duration, and severity. Pooled mean difference and odds ratio were calculated (random-effects model, RevMan version 5.3). Ten observational studies and two RCTs were included. The serum 25-hydroxy vitamin D level in the migraineurs was significantly lower than that in the nonmigraineurs [mean difference - 4.44 ng/mL (95% CI: -6.11, -2.77)] (low-GRADE evidence). Hypovitaminosis D was found to be significantly associated with migraine [OR: 1.95 (95% CI: 1.07, 3.58)] (low-GRADE evidence). As compared to placebo, oral vitamin D supplementation significantly reduced the monthly migraine-frequency [mean difference: -2.20 (95% CI: -3.04, -1.36)]. although it did not reduce the migraine-duration [mean difference: -16.00 hours per month (95% CI: -42.77, 10.76)] and migraine-severity score [standardized mean difference: -0.23 (95% CI: -0.79, 0.32)] (moderate-GRADE evidence). Serum 25-hydroxy vitamin D level was significantly lower in the migraineurs than that in the nonmigraineurs, and hypovitaminosis D was significantly associated with migraine. Oral vitamin D supplementation significantly reduced migraine-frequency, but not its duration and severity.


Malaria risk: estimation of the malaria burden.
Accurate estimates of the global burden of malaria are important for planning, monitoring and advocacy. Snow et al. attempt to address the shortcomings of previous estimates of the incidence of malaria caused by Plasmodium falciparum by combining current and historical data. However, we believe that the design of their model and its inputs have led to a significant overestimate of the malaria burden outside Africa--as in the example of the World Health Organization (WHO) western Pacific region (WPR), for which their model predicts 60 times the 2002 incidence reported by national malaria-control programmes.


Imaging of muscular denervation secondary to motor cranial nerve dysfunction.
The effects of motor cranial nerve dysfunction on the computed tomography (CT) and magnetic resonance imaging (MRI) appearances of head and neck muscles are reviewed. Patterns of denervation changes are described and illustrated for V, VII, X, XI and XII cranial nerves. Recognition of the range of imaging manifestations, including the temporal changes in muscular appearances and associated muscular grafting or compensatory hypertrophy, will avoid misinterpretation as local disease. It will also prompt the radiologist to search for underlying cranial nerve pathology, which may be clinically occult. The relevant cranial nerve motor division anatomy will be described to enable a focussed search for such a structural abnormality.


Prenatal detection of congenital renal malformations by fetal ultrasonographic examination: an analysis of 709,030 births in 12 European countries.
The study was performed to evaluate the prevalence of prenatal ultrasound diagnoses for renal anomalies in 20 registries of 12 European countries, and to compare the different prenatal scanning policies. Standardized data were acquired from 709,030 livebirths, stillbirths, and induced abortions during the study period of 2.5 years and transmitted for central analysis. At least one renal malformation was diagnosed in 1130 infants and fetuses. Prenatal diagnosis (PD) was given in 81.8% of all cases, 29% of these pregnancies were terminated. The highest detection rate was reported for unilateral multicystic dysplastic kidneys with 97% (102/105). An early diagnosis was documented for exstrophy of bladder at a mean gestational age of 18.5 weeks. Dilatations of the upper urinary tract were seen late in pregnancy at 28.3 weeks. Terminations of pregnancies (TOP) were performed in 67% (58/86) of the detected bilateral renal agenesis/dysgenesis, but only 4% of the unilateral multicystic dysplastic renal malformations (4/102). In about 1/3 of the cases, renal malformations are within the category of associated malformations, which include multiple non-syndromal malformations, chromosomal aberrations, and non-chromosomal syndromes. Renal malformations were detected in 2/3 of the associated category by the first prenatal ultrasound scan. Detection rates vary in the different countries of the European community due to diverse policies, ethical, and religious background. Countries with no routine ultrasound show the lowest rates in detection, and termination of pregnancy. Prenatally detected renal malformations should result in a careful examination for further anomalies. Prenatal ultrasound fulfills the needs of screening examinations and is a good tool in detecting lethal and severe renal malformations.


Identification of a novel cyclin required for the intrinsic apoptosis pathway in lymphoid cells.
We have identified an early step common to pathways activated by different forms of intrinsic apoptosis stimuli. It requires de novo synthesis of a novel cyclin, cyclin O, that forms active complexes primarily with Cdk2 upon apoptosis induction in lymphoid cells. Cyclin O expression precedes glucocorticoid and gamma-radiation-induced apoptosis in vivo in mouse thymus and spleen, and its overexpression induces caspase-dependent apoptosis in cultured cells. Knocking down the endogenous expression of cyclin O by shRNA leads to the inhibition of glucocorticoid and DNA damage-induced apoptosis due to a failure in the activation of apical caspases while leaving CD95 death receptor-mediated apoptosis intact. Our data demonstrate that apoptosis induction in lymphoid cells is one of the physiological roles of cyclin O and it does not act by perturbing a normal cellular process such as the cell cycle, the DNA damage checkpoints or transcriptional response to glucocorticoids.


Barriers to implementing an integrated care pathway for the last days of life in nursing homes.
this paper explores the barriers that needed to be overcome during the process of implementing an integrated care pathway for the last days of life as a way of developing quality end-of-life care in nursing homes. an action research methodology underpinned the study. Qualitative and quantitative data were collected in eight nursing homes before, during and after the implementation of the care pathway. six main barriers were identified: a lack of knowledge of palliative care drugs and control of symptoms at the end of life; lack of preparation for approaching death; not knowing when someone is dying or understanding the dying process; lack of multidisciplinary team working in nursing homes; lack of confidence in communicating about dying; some nursing homes are not ready or able to change. These findings highlight a functional 'rehabilitative' culture that may not be so appropriate in the current context of nursing home care, and one that makes implementing an integrated care pathway for the last days of life less straightforward than in other settings. it cannot be presumed that the implementation of a care pathway for the last days of life in nursing homes is straightforward. This study suggests that an action research framework was extremely useful in highlighting and overcoming some obstacles when developing evidence-based practice. Action at both local and public policy level is required to fully address barriers that prevent quality end-of-life care in nursing homes.


Serum biomarkers in interstitial lung diseases.
The use of biomarkers in medicine lies in their ability to detect disease and support diagnostic and therapeutic decisions. New research and novel understanding of the molecular basis of the disease reveals an abundance of exciting new biomarkers who present a promise for use in the everyday clinical practice. The past fifteen years have seen the emergence of numerous clinical applications of several new molecules as biologic markers in the research field relevant to interstitial lung diseases (translational research). The scope of this review is to summarize the current state of knowledge about serum biomarkers in interstitial lung diseases and their potential value as prognostic and diagnostic tools and present some of the future perspectives and challenges.


Significance of the interleukin-1 receptor antagonist/interleukin-1 beta ratio as a prognostic factor in patients with pulmonary sarcoidosis.
Various factors such as serum angiotensin-converting enzyme (sACE) activity, bronchoalveolar lavage (BAL) fluid lymphocyte percent, CD4/CD8 ratio, and shadows on chest radiograph have been identified as indexes of disease activity in patients with sarcoidosis. However, it remains to be confirmed whether these factors can predict clinical outcomes. To examine whether the interleukin-1 receptor antagonist (IL-1ra)/IL-1 beta ratio can predict the clinical course, we prospectively followed the clinical courses of 30 patients with pulmonary sarcoidosis 4 years after measurement of immunoreactive amounts of IL-1ra or IL-1 beta in the culture supernatants obtained from BAL fluid macrophages. Immunoreactive amounts of IL-1ra or IL-1 beta were measured using ELISA. Changes in pulmonary function, sACE activity, and shadows on chest radiographs during observation periods were evaluated as markers of changes in disease activity. We found that the patients whose shadows on chest radiographs showed improvement had a higher molar IL-1ra/IL-1 beta ratio than the patients whose shadows persistently remained 4 years after BAL examination (p < 0.05). The molar ratio was found to be positively correlated with improvement of percent vital capacity (p < 0.05) and negatively correlated with the ratio of sACE activity at the time of the last observation to sACE activity at the time of BAL (sACE(LAST)/sACE(BAL), p < 0.01). The sACE(LAST)/sACE(BAL) ratio was significantly lower in patients whose shadows on chest radiographs decreased than in those whose shadows remained unchanged (p < 0.005). The IL-1ra/IL-1 beta ratio in the BAL fluid macrophage culture supernatants in patients with pulmonary sarcoidosis could be a useful marker in predicting the persistence of granulomatous lesions (chronicity).


Lower lung cancer rates in Jewish smokers in Israel and the USA.
Lung cancer rates in Israeli Jews have remained stable over the last five decades and are much lower than in most developed countries despite high historical smoking rates. We compared lung cancer risk in Jews and non-Jews in Israel and in the United States. Data were derived from a population-based, case-control study in Israel (638 cases, 496 controls) to estimate lung cancer risk associated with smoking. Data were also acquired from a case-control study in the United States with information on religious affiliation (5,093 cases, 4,735 controls). Smoking was associated with lung cancer risk in all religion/gender groups in both studies. However, major differences in risk magnitude were noted between Jews and non-Jews; ever smoking was associated with a moderately elevated risk of lung cancer in Jewish men and women in Israel (OR = 4.61, 2.90-7.31 and OR = 2.10, 1.36-3.24, respectively), and in Jewish men and women in the United States (OR = 7.63, 5.34-10.90 and OR = 8.50, 5.94-12.17) but were significantly higher in Israeli non-Jewish men (OR = 12.96, 4.83-34.76) and US non-Jewish men and women (OR = 11.33, 9.09-14.12 and OR = 12.78, 10.45-15.63). A significant interaction between smoking and religion was evident in light, moderate and heavy male and female smokers. The differences in risk level between Israeli Jews and non-Jews could not be explained by lung cancer genetic risk variants which were identified in GWAS (genes in the CHRNA5, TERT and CLPTM1L regions). Data from the two studies support the notion of a reduced risk of lung cancer in Jewish compared to non-Jewish smokers in different areas of the world.


Intimate Relationships and Coronary Heart Disease: Implications for Risk, Prevention, and Patient Management.
Research and clinical services addressing psychosocial aspects of coronary heart disease (CHD) typically emphasize individuals, focusing less on the context of intimate relationships such as marriage and similar partnerships. This review describes current evidence regarding the role of intimate relationships in the development, course, and management of CHD. Having an intimate partner is associated with reduced risk of incident CHD and a better prognosis among patients, but strain (e.g., conflict) and disruption (i.e., separation, divorce) in these relationships are associated with increased risk and poor outcomes. These associations likely reflect mechanisms involving health behavior and the physiological effects of emotion and stress. Importantly, many other well-established psychosocial risk and protective factors (e.g., low SES, job stress, depression, and optimism) are strongly related to the quality of intimate relationships, and these associations likely contribute to the effects of those other psychosocial factors. For better or worse, intimate partners can also affect the outcome of efforts to alter health behaviors (physical activity, diet, smoking, and medication adherence) central in the prevention and management CHD. Intimate partners also influence-and are influenced by-stressful aspects of acute coronary crises and longer-term patient adjustment and management. Evidence on each of these roles of intimate relationships in CHD is considerable, but direct demonstrations of the value of couple assessments and interventions are limited, although preliminary research is promising. Research needed to close this gap must also address issues of diversity, disparities, and inequity that have strong parallels in CHD and intimate relationships.


Atropine methylbromide and glycopyrrolate. A comparative study during reversal of neuromuscular block.
Two quaternary anticholinergics, atropine methylbromide (methylatropine bromide, MAB) and glycopyrrolate (ROBINUL) were compared as adjuncts to neostigmine for the reversal of residual nondepolarising neuromuscular block. MAB 0.75 mg in combination with neostigmine 2 mg produced a marked initial rise in heart rate. This was significantly greater than that produced by the administration of glycopyrrolate 0.4 mg with neostigmine. The antisialogogue effects of the two anticholinergics were identical and the central nervous system status of the patients was similar. It is concluded that, with the doses used in this study, glycopyrrolate is a superior alternative to MAB and is the drug of choice if a quaternary ammonium anticholinergic is required.


CuInS2/ZnS-based QLED design and modelling for automotive lighting systems.
This work reports the design, manufacturing and numerical simulation approach of a 6-pixel (4.5mm2/pixel) electroluminescent quantum dot light emitting device (QLED) based on CuInS2/ZnS quantum dots as an active layer. Following a conventional thin-film deposition multilayer approach, the QLED device was fabricated. In addition, the electrical I-V curve was measured for each pixel independently, observing how the fabrication process and layer thickness have an influence in the shape of the plot. This experimental device fabricated, enabled us to create a computational model for the QLED based on the Transfer Hamiltonian approach to calculate the current density J(mA/cm2), the band diagram of the system, and the accumulated charge distribution. Besides, it is worth highlighting that the simulator allows the possibility to study the influence of different parameters of the QLED structure like the junction capacitance between the distinct multilayer set. Specifically, we found that Anode-HIL interface capacitance has a greater influence in the I-V plot shape. That junction capacitance plays an important role in the current increase and the QLED turn-on value when a forward voltage is applied to the device. Thanks to the simulator, that influence could be put under control by the selection of the optimal thickness and transport layers during the experimental fabrication process. This work is remarkable since it achieves to fit simulation and experiment results in an accurate way for electroluminescent QLED devices; particularly the simulation of the device current, which is critical when designing the automotive electronics to control these new nanotechnology lighting devices in the future.


[Relation between the intensity of low-angle equatorial reflections of x-ray diffraction patterns of frog skeletal muscle and sarcomere length].
Dependence of the intensities of low-angle equatorial reflections from frog live resting sartorius muscle on sarcomere length between 1.95 micron and 3.1 micron were studied in stretch and shortening regimes. It is found that intensities of the (10), (20), (30) and Z-reflections increase at sarcomere length increase from about 2 micron, reach maximum value at sarcomere length between 2.3 micron and 2.7 micron, and then fall at further increase of the sarcomere length. The (11) and (21) intensities decrease at sarcomere length increase. A conclusion is drawn that tetragonal lattice of the thin filaments near Z-line gives essential contribution to Z-reflection together with Z-line. It is proposed that hexagonal lattice of A-band and tetragonal lattice of the thin filaments distort each other at sarcomere length less than 2.3 micron and have the most order at sarcomere length between 2.3 micron and 2.7 micron. At further increase of the sarcomere length the packing of both lattices deteriorates apparently due to other factors than in the case of the short sarcomere length.


Absorbent bioactive aerogels based on germinated wheat starch and grape skin extract.
This study aimed to produce water-absorbent bioactive aerogels using biodegradable raw materials, wheat starch and poly ethylene oxide (PEO), and derived from agro-industrial residues (grape skin) obtained in the wine industry. The aerogels were produced using germinated wheat starch (GWS), with and without PEO, and incorporating grape skin extract (GSE) at concentrations of 5 and 10 % (w/w). The GSE was evaluated for total and individual phenolic compounds, anthocyanins, and antioxidant activity. The starch aerogels were characterized for morphology, density, porosity, functional groups by FT-IR, relative crystallinity and diffraction pattern, water absorption capacity, antioxidant activity, and in vitro release profile of phenolic compounds in food simulant medium. The total phenolic compounds in GSE was 226.25 ± 0.01 mg equivalent of gallic acid/g GSE. The aerogels showed low density and high porosity. All aerogels demonstrated high water absorption capacity (581.4 to 997.5 %). The antioxidant activity of the aerogels increased with increasing GSE concentration and the addition of PEO. The aerogels could release GSE gradually for up to 120 days in the hydrophilic simulant medium and 240 h for the hydrophobic medium. Starch-based aerogels with GSE showed potential to be applied as exudate absorbers with antioxidant activity to develop active food packaging.


Selective estrogen-receptor modulators.
Tamoxifen is useful for adjuvant treatment of breast cancer and in some women for the prevention of breast cancer. The risk-benefit ratio in regard to the skeleton and perhaps other organ systems may very well be different for postmenopausal versus premenopausal women. In postmenopausal women, tamoxifen (20 mg/d) increased BMD in the spine and perhaps the hip; however, the effect on fracture risk is unclear. Therefore, for postmenopausal women with osteoporosis, consideration should be given to the addition of an agent that is shown to have efficacy against fractures (such as bisphosphonates), even while these women are on tamoxifen. For women at only modest or moderate risk, with bone density above the osteoporosis range (T score above -2.5) and no major fracture history, tamoxifen is probably adequate for 5 years of use. Potentially serious adverse effects include venous thromboembolism, uterine cancer, benign uterine disease, and cataracts. Raloxifene (60 mg/d) protects against vertebral fractures over 4 years in women with osteoporosis, produces small increases in bone mass of the spine, hip, and total body, and reduces bone turnover in postmenopausal women with or without osteoporosis. No significant effect has yet been demonstrated on nonvertebral fractures after 4 years of treatment. Raloxifene has the additional benefit of substantially reducing the risk of ER-positive invasive breast cancer and does not increase the risk of uterine disease. Raloxifene increases the risk of venous thromboembolic disease to the same degree as tamoxifen and estrogen. Therefore, SERMS and estrogens are generally contraindicated in women with a previous history of venous thromboembolism or those who are at significantly increased risk. Raloxifene is probably most useful in women who have osteoporosis (T score = -2.5) or who are at risk (T score less than -1.5 with clinical risk factors) in the middle menopausal period (age 55-65) or in the early menopausal period in women who have no significant hot flashes. At this stage in life, vertebral fractures are common, but hip fractures are not. Therefore, women who take raloxifene can expect a reduction in the likelihood of having a vertebral fracture, and possibly breast cancer. The lack of definitive efficacy against hip fracture is not a major deterrent to use of this agent in this age group because hip fracture risk is very low. Raloxifene might not be the treatment of choice for elderly women who are at particularly high risk of hip fracture.


The effect of triamcinolone acetonide on laser-induced choroidal neovascularization in mice using a hypoxia visualization bio-imaging probe.
Hypoxic stress is a risk factor of ocular neovascularization. Hypoxia visualization may provide clues regarding the underlying cause of angiogenesis. Recently, we developed a hypoxia-specific probe, protein transduction domain-oxygen-dependent degradation domain-HaloTag-Rhodamine (POH-Rhodamine). In this study, we observed the localization of HIF-1α proteins by immunohistochemistry and the fluorescence of POH-Rhodamine on RPE-choroid flat mounts. Moreover, we compared the localization of POH-Rhodamine with pimonidazole which is a standard reagent for detecting hypoxia. Next, we investigated the effects of triamcinolone acetonide (TAAC) against visual function that was evaluated by recording electroretinogram (ERG) and choroidal neovascularization (CNV) development. Mice were given laser-induced CNV using a diode laser and treated with intravitreal injection of TAAC. Finally, we investigated POH-Rhodamine on CNV treated with TAAC. In this study, the fluorescence of POH-Rhodamine and HIF-1α were co-localized in laser-irradiated sites, and both the POH-Rhodamine and pimonidazole fluorescent areas were almost the same. Intravitreal injection of TAAC restored the reduced ERG b-wave but not the a-wave and decreased the mean CNV area. Furthermore, the area of the POH-Rhodamine-positive cells decreased. These findings indicate that POH-Rhodamine is useful for evaluating tissue hypoxia in a laser-induced CNV model, suggesting that TAAC suppressed CNV through tissue hypoxia improvement.


Zn++ inhibits both tumor necrosis factor-mediated DNA fragmentation and cytolysis.
The cellular events involved in direct tumor-cell destruction by tumor necrosis factor (TNF) are still incompletely understood, but a role of endonucleases has been suggested. In the present study we have analyzed in detail the effect of Zn++, an inhibitor of endonucleases, on TNF-mediated DNA-fragmentation and on cytolysis in Actinomycin-D-pre-treated WEHII 64-S cells. Beginning 2 hr after addition of TNF, a rapid degradation of cellular DNA is observed, as evidenced by release of 3H-Thymidine (TdR) label from nuclei into cytoplasm. TNF-mediated lysis of WEHII64-S cells begins at 3 hr and reaches plateau levels at 7 hr. Addition of Zn++ to TNF-treated WEHII64 cells completely abrogates DNA fragmentation at ImM. Of greater importance is the fact that Zn++ treatment also completely blocks TNF-mediated cytolysis of the target cells. Concentrations-between 0.1 and I mM ZnSO4 prevent cell death, as assessed by chromium-release and Trypan blue dye exclusion. In addition, ZnCl2, but not other divalent cations like CaCl2, MgSO4 and CuSO4 in the same concentration range, prevents cell death as well, demonstrating that the effect in fact is mediated by Zn++. Zn++ added 2 hr after TNF treatment, still effectively inhibits cell lysis, indicating that it acts at a late stage after binding of TNF to its receptor. Our data suggest that activation of endonucleases is not an accompanying effect but an essential step in TNF-mediated tumor-cell destruction.


Expression of human tumor necrosis factor-like weak inducer of apoptosis in patients with systemic lupus erythematosus.
The aim of this study was to compare the mRNA and serum expression of tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) in patients with systemic lupus erythematosus (SLE) and healthy controls. Sixty-two SLE patients and 15 healthy controls were recruited in the study. TWEAK messenger RNA (mRNA) expression in peripheral blood mononuclear cells (PBMCs) from 33 of 62 patients was detected by relative quantification RT-PCR. TWEAK concentrations in the sera of all 62 patients were measured by ELISA. TWEAK mRNA expressions in PBMCs were decreased in SLE patients compared with healthy controls. Lower TWEAK mRNA expression was also found in the active SLE patients when compared to inactive ones. However, there was no significant difference between patients with lupus nephritis (LN) and those without. The level of serum TWEAK (sTWEAK) in SLE patients was increased when compared to healthy controls. In addition, the sTWEAK level was higher in SLE patients with vasculitis than those without vasculitis, and so was in comparison between patients with and without headache. Nevertheless, no significant differences were found between active SLE patients and inactive patients, or between LN patients and non-LN SLE patients. In this study, patients with SLE express low levels of TWEAK mRNA but high levels of sTWEAK. Additionally, sTWEAK level was associated with several clinical manifestations of SLE, indicating that TWEAK may play a complex role in SLE.


Variation in acoustic overstimulation changes tinnitus characteristics.
Tinnitus often occurs after exposure to loud noise. This raises the question of whether repeated exposure to noise increases the risk of developing tinnitus. We thus studied tinnitus development after repeated acoustic overstimulation using startle and auditory brainstem-response techniques applied to Mongolian gerbils. Noise with bandwidths ranging from 0.25 up to 0.5 oct were used for repeated acoustic overstimulation. Auditory brainstem response measurements revealed similar threshold shifts in both groups of up to about 30 dB directly after the acoustic overstimulation. We identified an upper limit in threshold values, which was independent of the baseline values before the noise exposure. Several weeks after the acoustic overstimulation, animals with the noise bandwidth of 0.25 oct showed a permanent threshold shift, while animals of the group with the 0.5-oct noise band featured only a temporary threshold shift. We thus conclude that the threshold shift directly after noise exposure cannot be used as an indicator for the upcoming threshold level several weeks later. By using behavioral measurements, we investigated the frequency-dependent development of tinnitus-related changes in both groups and one group with 1-oct noise bandwidth. The number of animals that show tinnitus-related changes was highest in animals that received noise with the bandwidth 0.5 oct. This number was, in contrast to the number of animals in the 0.25-oct bandwidth, not significantly increased after repeated overstimulation. The frequency distribution of tinnitus-related changes ranged from 4 to 20 kHz. In the group with the narrow-band noise (0.25 oct) changes center at one frequency range from 10 to 12 kHz. In the group with the broader noise band (0.5 oct), however, two peaks at 8-10 kHz and at 16-18 kHz were found, which suggests that different mechanisms underlie the tinnitus development.


Pharmacogenetic Predictors of Treatment-Related Toxicity Among Children With Acute Lymphoblastic Leukemia.
The aim of this review is to summarize the most recent and most robust pharmacogenetic predictors of treatment-related toxicity (TRT) in childhood acute lymphoblastic leukemia (ALL). Multiple studies have examined the toxicities of the primary chemotherapeutic agents used to treat childhood ALL in relation to host genetic factors. However, few results have been replicated independently, largely due to cohort differences in ancestry, chemotherapy treatment protocols, and definitions of toxicities. To date, there is only one widely accepted clinical guideline for dose modification based on gene status: thiopurine dosing based on TPMT genotype. Based on recent data, it is likely that this guideline will be modified to incorporate other gene variants, such as NUDT15. We highlight genetic variants that have been consistently associated with TRT across treatment groups, as well as those that best illustrate the underlying pathophysiology of TRT. In the coming decade, we expect that survivorship care will routinely specify screening recommendations based on genetics. Furthermore, clinical trials testing protective interventions may modify inclusion criteria based on genetically determined risk of specific TRTs.


Comparative transcriptomics reveals unique pine wood decay strategies in the Sparassis latifolia.
Sparassis latifolia is a valuable edible mushroom, growing on fresh pine wood sawdust substrate. However, the mechanistic bases are poorly understood. The gene expression profiles of S. latifolia were analyzed from submerged cultures with fresh pine wood sawdust substrate for different time (0 h, 1 h, 6 h, 1 day, 5 days, and 10 days, respectively). The total number of differentially expressed genes (DEGs) identified under pine sawdust inducing was 2,659 compared to 0 h (CK). And 1,073, 520, 385, 424, and 257 DEGs were identified at the five time points, respectively. There were 34 genes in common at all inoculated time points, including FAD/NAD(P)-binding domain-containing protein, glucose methanol choline (GMC) oxidoreductase, flavin-containing monooxygenase, and taurine catabolism dioxygenase. Weighted gene co-expression analysis (WGCNA) was then used to compare the molecular characteristics among the groups and identified that the blue module had the highest correlation with the time induced by pine wood sawdust. There were 102 DEGs out of 125 genes in the blue model, which were most enriched in nitronate monooxygenase activity, dioxygenase activity, and oxidation-reduction process GO terms (p < 0.05), and peroxisome in KEGG pathway. This may provide clues into mechanisms that S. latifolia can grow on fresh pine wood sawdust substrate.


Determinants of leptin in human breast milk: results of the Ulm SPATZ Health Study.
Leptin in human breast milk has been implicated as a potential regulator of early-life metabolic programming. We comprehensively investigated the influence of maternal body mass index (BMI) and non-adiposity associated determinants on breast milk leptin concentration at 6 weeks, 6 months, and 1 year postpartum. The Ulm SPATZ Health Study consists of 1006 newborns and their mothers recruited from the general population in the University Medical Center Ulm, Southern Germany, in 2012/2013. Leptin concentration was measured in skimmed breast milk using commercially available ELISA (R&D System). Generalized estimating equations (GEE) accounting for repeated measures were used to calculate beta coefficients and 95% confidence intervals for association of potential demographic and lifestyle related determinants of hormone concentration with BMI-standardized leptin z-scores. Leptin concentration was measured in breast milk samples obtained from 694 mothers at approximately 6 weeks (n = 668), 6 months (n = 445), and 1 year (n = 69) postpartum. Differences in crude leptin concentrations between collection times were mostly explained by changes in BMI, breastfeeding frequency, and breast milk fat concentration. Positive associations between BMI and leptin were nonlinear and stronger among lower BMI subjects. Upon standardization, residual leptin concentrations were associated with maternal birth country, parity, age, and smoking history. Breast milk leptin concentration is primarily determined by adiposity-related factors. Studies using BMI as a proxy measure for adiposity should account for an observed nonlinear association with leptin, which may be especially important in determining causal associations with health outcomes from this and other adiposity-related hormones in breast milk.


Surface metal-EDTA coordination layer activates NixFe3-xO4 spinel as an outstanding electrocatalyst for oxygen evolution reaction.
Nickel-iron oxides are competitive electrocatalysts for oxygen evolution reaction, but their practical applications are restricted by the less-than-desirable intrinsic activity and working stability. To tackle the challenge, surface coordination chemistry is applied to the nickel-iron oxides through a complex-assisted in-situ crystal growth strategy. The ethylenediaminetetraacetate (EDTA) coordinated NixFe3-xO4 (NixFe3-xO4-EDTA) is prepared by a simple one-pot hydrothermal process. The coordinated EDTA molecules can deeply alter the surface coordination structure of the NixFe3-xO4. The NixFe3-xO4-EDTA demonstrates outstanding intrinsic activity towards oxygen evolution reaction, requiring only a small overpotential of 180 mV to reach 10 mA cm-2 in 1.0 M KOH. Moreover, the NixFe3-xO4-EDTA exhibits extremely stable long-term working stability. Density functional theory calculations show that the highly enhanced intrinsic activity is attributed to the surface coordinated EDTA-induced favorable electronic structure and coordination environment, which tunes the adsorption strength of the intermediates and optimizes the energetics of the elementary steps, while the high stability is ascribed to the strong coordination ability of EDTA.


Thermal desorption GC-MS as a tool to provide PAH certified standard reference material on particulate matter quartz filters.
Reference materials for particulate matter (PM) on filter media are not available for the quantification of polycyclic aromatic hydrocarbons (PAHs) in ambient air. This is due to the difficulty of obtaining reference material that has a homogeneous distribution on a filter surface that is large enough for characterization and distribution. High volume sample filters from different locations and seasons were considered to validate the feasibility of the use of quartz filters as reference material for PAH concentrations. A rapid thermal desorption (TD) technique coupled with gas chromatography/mass spectroscopy was applied to characterise the material for the content of fifteen different PAHs. TD technique allowed for rapid and accurate analysis of small sections of filter (5mm diameter), leaving enough material for the production of twenty sub-filter cuts (42 mm diameter) that could be used for distribution and control. Stability and homogeneity tests required for material certification were performed as indicated by the ISO guide 34:2009 and ISO 35:2006. The contribution of the heterogeneous distribution of PAHs on the filter surface resulted generally lower than 10% and higher for more volatile PAHs. One year of storage at -18°C indicated no significant variation in PAH concentrations. Nevertheless, a methodology for shipping and storing of the filter material at ambient temperature in especially designed plastic envelopes, was also shown to allow for stabile concentrations within twenty days. The method accuracy was confirmed by the analysis of NIST SRM 1649a (urban dust) and PAH concentrations were validated against the reference values obtained from an inter-laboratory exercise. In the case of benzo[a]pyrene for masses quantified between 100 pg and 10 ng the TD method provided expanded uncertainties of circa 10%, while the inter-laboratory reference value uncertainties ranged between 15 and 20%. The evaluation of these results supports the use of the presented methodology as a valid approach for the certification of PAH concentrations in PM10 quartz filters. The methodology allows for the production of a certificate of analysis for a single high volume filter, the concentration of which can easily be adjusted by selecting an appropriate sampling location.


Nitrogen-doped carbon nanotubes enhanced Fenton chemistry: Role of near-free iron(III) for sustainable iron(III)/iron(II) cycles.
The sluggish kinetics of Fe(II) recovery strongly impedes the scientific progress of Fenton reaction (Fe(II)/H2O2) towards practical application. Here, we propose a novel mechanism that metal-free nitrogen-doped carbon nanotubes (NCNT) can enhance Fenton chemistry with H2O2 as electron donors by elevating the oxidation potential of Fe(III). NCNT remarkably promotes the circulation of Fe(III)/Fe(II) to produce hydroxyl radical (•OH) with excellent stability for multiple usages (more than 10 cycles) in the NCNT/Fe(III)/H2O2 system. Although carbonyl on NCNT can act as the electron supplier for Fe(III) reduction, the behavior of NCNT is distinct from common reductants such as hydroxylamine and boron. Electrochemical analysis and density functional theory calculation unveil that nitrogen sites of NCNT can weakly bind with Fe(III) to elevate the oxidation potential of Fe(III) (named near-free Fe(III), primarily FeOH2+) at pH ranging from 2.0 to 4.0. Without inputs of external stimulations or electron sacrificers, near-free Fe(III) can promote H2O2 induced reduction of Fe(III) to initiate Fenton chain reactions for long-lasting generation of •OH. To our delight, it is a common property of N-doped carbon materials (e.g., graphene, carbon nanofibers, and acetylene black), our research thus provides a novel, sustainable, and green strategy for promoting Fenton chemistry.


Metabolite analysis of biological fluids and tissues by proton nuclear magnetic resonance spectroscopy.
NMR-based biochemical profiling of natural products has become popular due to the development of high-resolution instruments (>400 MHz) and cryogenically cooled probes/preamplifiers, by increasing the sensitivity of NMR instruments several fold and reducing instrument noise levels. NMR provides a rapid, nondestructive, high-throughput method that requires minimal sample preparation, therefore maintaining the biological integrity of the sample. One-dimensional (1D) solution-state (1)H NMR is used in untargeted sample screening (metabolomics/metabonomics) to gain insight into spectral pattern changes associated with samples of different origins. Metabolomics and metabonomics contextually explains the systematic and quantitative measurement of metabolites that are produced from the biochemical reactions of living systems. This chapter describes some commonly used (1)H NMR experiments for identification and quantification of small molecular weight, water soluble metabolites in biological samples, some considerations for choosing the correct NMR experiment, and sample preparation protocols for isolating metabolites from a number of biological sample types.


Conjugation of protein to immunostimulatory DNA results in a rapid, long-lasting and potent induction of cell-mediated and humoral immunity.
Immunostimulatory DNA sequences (ISS) are a potent Th1 adjuvant. We hypothesized that conjugation of ISS to protein antigens would strongly enhance their immunogenicity because both antigen and adjuvant (ISS) would be delivered to the same locale/antigen-presenting cell. To test this hypothesis, we conjugated a 22-mer immunostimulatory oligodeoxynucleotide (ISS-ODN) to two test antigens of differing intrinsic immunogenicity, namely Escherichia coli beta-galactosidase and the HIV-1 envelope glycoprotein gp120. We show that the antigen-ISS conjugates rapidly induce Th1 cells secreting high levels of IFN-gamma, strong CTL activity, and high titer IgG2a and HIV-neutralizing antibodies, exceeding gene and protein vaccination alone or immunization with mixtures of antigen and ISS-ODN. The data suggest that this procedure generates a novel and unique vaccine that rapidly triggers strong humoral and cell-mediated immunity.


Faecal calprotectin levels after rifaximin treatment in patients with irritable bowel syndrome with diarrhoea: A single-center prospective study.
Although unclear, the pathophysiology of irritable bowel syndrome (IBS) is considered to be multifactorial. Recent studies have suggested that IBS is a low-grade inflammatory bowel disease (IBD) with high faecal calprotectin (FC) levels. Rifaximin is a potential therapeutic agent for IBS with diarrhoea (IBS-D) due to its ability to decrease FC levels. This study evaluated the role of FC as a follow-up marker of IBS-D after short-course rifaximin treatment. Ninety-six patients with chronic diarrhoea who fulfilled the Rome IV criteria for IBS-D were enrolled in this study from outpatient clinics. After excluding 18 patients who did not complete the study due to treatment noncompliance or missing follow-up visits, 78 patients (mean age, 39.2 ± 6.9 years) with IBS-D and elevated baseline FC levels were included. An FC level of <50 μg/g was considered normal. Abdominal symptoms were assessed using a Likert scale. All patients received oral rifaximin (550 mg three times daily) for 2 weeks, followed by assessment for abdominal symptoms and FC levels; the treatment was extended to 4 weeks if FC levels remained elevated after 2 weeks of treatment. FC levels normalised in 66 (84.6%) patients, including 60 and 6 patients treated for 2 and 4 weeks, respectively. The remaining 12 (15.4%) patients with persistently elevated FC levels despite 4 weeks of treatment also showed a significant decline in their final FC levels compared with the baseline, accompanied with a significant improvement in abdominal symptoms (p = 0.001). A cutoff baseline FC value of 148.5 μg/g could predict non-responders with 100% sensitivity and 50% specificity. Short-course oral rifaximin treatment results in FC normalisation in IBS-D patients with high baseline FC values. Therefore, FC should be considered as a biomarker of follow-up after rifaximin treatment for IBS-D.


Inactivation of two homologues of proteins presumed to be involved in the desiccation tolerance of plants sensitizes Deinococcus radiodurans R1 to desiccation.
Mutational inactivation of the genes designated DR1172 and DRB0118 in Deinococcus radiodurans R1 greatly sensitizes this species to desiccation, but not to ionizing radiation. These genes encode proteins that share features with the desiccation-induced LEA76 proteins of many plants and the PCC13-62 protein of Craterostigma plantagineum, suggesting that D. radiodurans may serve as a useful model for the study of desiccation tolerance in higher organisms.


Extra-intestinal malignancies in inflammatory bowel disease: results of the 3rd ECCO Pathogenesis Scientific Workshop (III).
The incidence of lymphoproliferative disorders (LD) is increasing in developed countries. Patients with inflammatory bowel disease (IBD) exposed to thiopurines are at additional risk of three specific forms of LD: Epstein-Barr-Virus-related post-transplant like LD, hepato-splenic T-cell lymphoma and post-mononucleosis lymphoproliferation. The risk of the two latter forms of LD can be reduced when considering specific immunosuppressive strategies in young males. It is still unclear whether the risk of uterine cervix abnormalities is increased in IBD women, irrespective of the use of immunosuppressants. Given the excess risk demonstrated in various other contexts of immunosuppression, it is currently recommended that all women with IBD, particularly those receiving immunosuppressants, strictly adhere to a screening program of cervical surveillance and undergo vaccination against HPV, when appropriate. Patients with IBD receiving immunosuppressants are at increased risk of skin cancers. The risk of non-melanoma skin cancer is notably increased in patients receiving thiopurines. Recent data suggest that the risk of melanoma is mildly increased in patients exposed to anti-TNF therapy. All IBD patients should adhere to a program of sun protection and dermatological surveillance, whose details should take into account the other non-IBD-related risk factors.


Detection of low-abundance bacterial strains in metagenomic datasets by eigengenome partitioning.
Analyses of metagenomic datasets that are sequenced to a depth of billions or trillions of bases can uncover hundreds of microbial genomes, but naive assembly of these data is computationally intensive, requiring hundreds of gigabytes to terabytes of RAM. We present latent strain analysis (LSA), a scalable, de novo pre-assembly method that separates reads into biologically informed partitions and thereby enables assembly of individual genomes. LSA is implemented with a streaming calculation of unobserved variables that we call eigengenomes. Eigengenomes reflect covariance in the abundance of short, fixed-length sequences, or k-mers. As the abundance of each genome in a sample is reflected in the abundance of each k-mer in that genome, eigengenome analysis can be used to partition reads from different genomes. This partitioning can be done in fixed memory using tens of gigabytes of RAM, which makes assembly and downstream analyses of terabytes of data feasible on commodity hardware. Using LSA, we assemble partial and near-complete genomes of bacterial taxa present at relative abundances as low as 0.00001%. We also show that LSA is sensitive enough to separate reads from several strains of the same species.


Knowledge and Awareness of Primary Teeth and Their Importance among Parents in Bengaluru City, India.
Often people responsible for the oral care of children feel or believe that since primary teeth will eventually shed, it is not worthwhile to spend time/money on providing good oral health to children. Parents are the ones who take care of their children and make decisions for them. Hence, they should have knowledge about primary teeth, their health and caring in order to build confidence in their children through tiny teeth. To assess the knowledge of primary teeth and their importance among parents with children below 12 years. A total of 1,000 questionnaires containing questions written both in English and in the local language (Kannada) were prepared for data collection and were personally distributed to parents visiting dental clinics for their children's dental treatment. Both descriptive statistics and Chi-square test were used. Complaints related to dental caries constituted 82% of children visiting dental clinics among children in Bengaluru city. Only 39% of respondents were aware of all functions of primary teeth. The present study revealed that the parents of Bengaluru city had superficial or partial knowledge of primary teeth and that there is a need to improve this awareness. How to cite this article: Setty JV, Srinivasan I. Knowledge and Awareness of Primary Teeth and Their Importance among Parents in Bengaluru City, India. Int J Clin Pediatr Dent 2016;9(1):56-61.


Evidence for a role for cyclic AMP in modulating the action of 5-HT and an excitatory neuropeptide, FLP17A, in the pharyngeal muscle of Caenorhabditis elegans.
The feeding activity of the nematode Caenorhabditis elegans is regulated by an anatomically well-defined network of 20 enteric neurones that employs small molecule and neuropeptidergic signalling. Two of the most potent excitatory agents are 5-HT and the neuropeptide FLP17A. Here we have examined the role of cAMP in modulating their excitatory actions by pharmacological manipulation of the level of cAMP. Application of the membrane permeable cAMP analogue, dibutyryl-cAMP (1 microM), enhanced the excitatory response to both FLP17A and 5-HT. Furthermore, the adenylyl cyclase activator, forskolin (50 nM), significantly enhanced the excitatory response to both FLP17A and 5-HT. The phosphodiesterase inhibitor, ibudilast (10 microM), enhanced the excitatory response to FLP17A. The protein kinase inhibitor, H-9 dihydrochloride (10 microM) significantly reduced the excitatory response to 5-HT. H-9 dihydrochloride also had a direct effect on pharyngeal activity. The effect of FLP17A and 5-HT on two mutants, egl-8 (loss-of-function phospholipase-Cbeta) and egl-30 (loss-of-function Galphaq) was also investigated. Both these mutants have a lower pharyngeal pumping rate than wild-type which has to be considered when interpreting the effects of these mutations on the excitatory responses to FLP17A and 5HT. However, even taking into consideration the lower basal activity of these mutants, it is clear that the percentage increase in pharyngeal pumping rate induced by FLP17A is greatly reduced in both mutants compared to wild-type. In the case of 5-HT, the effect of the mutant backgrounds on the response was less pronounced. Overall, the data support a role for cAMP in modulating the excitatory action of both FLP17A and 5-HT on C. elegans pharyngeal pumping and furthermore implicate an EGL-30 dependent pathway in the regulation of the response to FLP17A.


The surface activity of the alveolar lining layer of guinea-pig lung following anaphylaxis.
The surface activity and lipid composition of alveolar extracts of guinea-pig lung following anaphylaxis have been studied. The extracts showed a reduced ability to lower surface tension on compression of the surface film which was maximal 30 min after challenge. No significant changes in the lipid content were found but there was a marked increase in the soluble solids 10 min after anaphylactic shock. The significance of these findings is discussed.


Experimental models of tracheobronchial stenoses: a useful tool for evaluating airway stents.
Stent implantation is a conservative alternative to open operation for treating benign tracheobronchial strictures. Most of the presently available stents were primarily designed for endovascular use. Their respiratory use entails a risk of iatrogenic complications. From a scientific and from an ethical point of view these risks justify preclinical evaluation of new respiratory stents in experimental models of central airway stenoses. Therefore, an attempt was made to develop such models in piglets and adult minipigs. Tracheal stenoses were obtained by creating first a segmental tracheomalacia through extramucosal resection of cartilaginous arches. The fibrous component of the stenoses was then obtained through bronchoscopic application of a caustic agent causing progressive deep mucosal and submucosal injury. Stenoses of the main bronchi were created by topical application of the caustic agent only. These models demonstrated the typical features of benign fibromalacic tracheobronchial stenoses with constant recurrence after mechanical dilation. Preliminary experiments showed that short-term problems of tolerance of stent prototypes are easily demonstrable in these models. These experimental models, which simulate quite realistically human diseases, offer the opportunity to perfect new tracheobronchial stents specifically designed for respiratory use and to evaluate their long-term tolerance before their use in humans.


Tracheotomy and tracheostomy tube placement in cattle.
Either as an emergency treatment or as part of therapy, being able to perform a tracheotomy and place a tracheostomy tube can be very useful for the bovine practitioner. This article presents different situations in which performing a tracheotomy and placing a tracheostomy tube might be indicated. Then the procedure itself is described, with an emphasis on some key points that help facilitate the surgery. Different tubes are presented, and the management of the surgery site is discussed. Finally, complications associated with the procedure and their management are explored.


Dynamics of consumer-resource reaction-diffusion models: single and multiple consumer species.
A consumer-resource reaction-diffusion model with a single consumer species was proposed and experimentally studied by Zhang et al.(Ecol Lett 20:1118-1128, 2017). Analytical study on its dynamics was further performed by He et al.(J Math Biol 78:1605-1636, 2019). In this work, we completely settle the conjecture proposed by He et al.(J Math Biol 78:1605-1636, 2019) about the global dynamics of the consumer-resource model for small yield rate. We then study a multi-species consumer-resource model where all the consumer species compete with each other through depression of the limited resources by consumption and there is no direct competition between them. We show that in this case, all consumer species persist uniformly, which implies that "competition exclusion" phenomenon will never happen. We also clarify its dynamics in both homogeneous and heterogeneous environments under various circumstances.