Prism representation: a 3D ray-tracing algorithm for radiotherapy applications.
Computing the intersection of a line with a volume, or 'ray tracing' as it is commonly known, is an integral component of three-dimensional radiotherapy dose calculation algorithms. Examples of ray tracing include the intersection of a ray from the radiation source with the patient, with heterogeneous volumes within the patient and with beam-modifying devices, such as a wedge or compensator. Ray tracing is also of primary importance in the field of three-dimensional computer graphics. Through the process of ray tracing, various display features, such as hidden surfaces, shadows, reflection and refraction, can be rendered simply and with startling realism. Advances have recently been made in three-dimensional ray-tracing methods in computer graphics. Due to the similarity of ray tracing in three-dimensional computer graphics and radiotherapy, these new techniques have an immediate application to the ray-tracing problems in three-dimensional radiotherapy dose calculations. The purpose of this paper is to present these advances and illustrate their use in radiation therapy.


A Monogenic Disease with a Variety of Phenotypes: Deficiency of Adenosine Deaminase 2.
Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive autoinflammatory disorder associated with ADA2 mutations. We aimed to investigate the characteristics and ADA2 enzyme activities of patients with DADA2 compared to non-DADA2 patients. This is a descriptive study of 24 patients with DADA2 who were admitted to the Adult and Pediatric Rheumatology, Pediatric Haematology, and Pediatric Immunology Departments of Hacettepe University. All ADA2 exons were screened by Sanger sequencing. Serum ADA2 enzyme activity was measured by modified spectrophotometric method. Twenty-four patients with DADA2 were included: 14 with polyarteritis nodosa (PAN)-like phenotype (Group 1); 9 with Diamond-Blackfan anemia (DBA)-like features, and 1 with immunodeficiency (Group 2). Fourteen PAN-like DADA2 patients did not have the typical thrombocytosis seen in classic PAN. Inflammatory attacks were evident only in Group 1 patients. Serum ADA2 activity was low in all patients with DADA2 except one, who was tested after hematopoietic stem cell transplantation. There was no significant difference in ADA2 activities between PAN-like and DBA-like patients. In DADA2 patients with one ADA2 mutation, serum ADA2 activities were as low as those of patients with homozygote DADA2. ADA2 activities were normal in non-DADA2 patients. ADA2 mutations were affecting the dimerization domain in Group 1 patients and the catalytic domain in Group 2 patients. We suggest assessing ADA2 activity along with genetic analysis because there are patients with one ADA2 mutation and absent enzyme activity. Our data suggest a possible genotype-phenotype correlation in which dimerization domain mutations are associated with PAN-like phenotype, and catalytic domain mutations are associated with hematological manifestations.


Undertreated breast cancer in the elderly.
The effect of undertreatment with adjuvant hormonal therapy, chemotherapy, or radiation was studied in elderly women with breast cancer. A prospectively maintained database was used to identify women undergoing potentially curative surgery between 1978 and 2012. The presentation, pathologic findings, treatment, and outcomes of 382 women over 70 were compared to the findings in 2065 younger patients. Subsequently, conventionally treated and undertreated elderly patients were identified and their characteristics and outcomes were compared. Both young and old patients presented most frequently with mammographic findings, but older patients presented more frequently with mammographic masses while younger patients presented more frequently with mammographic calcifications. Cancers of older patients were significantly more favorable than cancers in younger patients: smaller, with more infiltrating lobular, fewer ductal carcinoma in situ, and more frequently estrogen receptor positive and fewer were poorly differentiated. Elderly patients had less axillary sampling, fewer mastectomies, less adjuvant radiation therapy, and more hormonal therapy. Fifty-one percent of the 382 elderly patients were undertreated by conventional criteria. Undertreated patients were more frequently in situ, better differentiated, smaller, and more often estrogen receptor positive. Forty-four percent of the undertreated patients died during followup without disease recurrence. Despite undertreatment, local and distant disease-free survival was comparable to patients who were not undertreated.


Computed tomography in the planning and evaluation of therapeutic stereotaxic surgical procedures of the brain.
Preoperative and serial postoperative computed tomographic (CT) scans were obtained in 38 patients having either stereotaxic thalamotomy, mesencephalotomy, or a cingulumotomy to determine the relevance of the preoperative examination and to evaluate the site and evolution of the surgical lesion. Of the preoperative examinations, 55% were abnormal. The consequences of the stereotaxic procedure were identified in the first 2 postoperative weeks in 26 of the 28 patients having thalamotomy, six of the nine patients having mesencephalotomy, and all three patients having cingulumotomy as a diffuse low-density area (mean attenuation value, 18 Hounsfield units). A central core of increased attenuation due to an intralesional hemorrhage was present on the early postoperative scan in 17% of patients. The late residual lesion studied in seven patients was considerably smaller than the early abnormality. The appearances and temporal sequence of the postsurgical CT changes suggest the early abnormality is due to edema and the late lesion to coagulative necrosis. The findings suggest CT has a role in the preoperative assessment of patients having stereotaxic surgery in defining the target and predicting the stereotaxic coordinates, while postoperatively it documents the site of the lesion and can determine the basis of a complication.


Spexin may induce mitochondrial biogenesis in white and brown adipocytes via the hypothalamus-pituitary-thyroid (HPT) axis.
The present study aimed to investigate the effect of the intracerebroventricular (icv) administration of spexin on the hypothalamus-pituitary-thyroid (HPT) axis (TRH, TSH, T4 and T3 hormones) and energy expenditure (PGC-1α and UCP1 genes) in white adipose (WAT) and brown adipose tissues (BAT) in rats. Furthermore, the study aimed to determine the effects of spexin on food-water consumption and body weight of rats. The study was conducted with 40 male rats that were divided into 4 groups: Control, Sham, Spexin 30 and Spexin 100 (n = 10). Spexin (1 μl/hour) was administered to rats other than those in the control group for 7 days with osmotic minipumps intracerebroventricularly, artificial cerebrospinal fluid (vehicle) was administered to the Sham group, and 30 nMol and 100 nMol spexin was infused to the Spexin 30 and Spexin 100 groups, respectively. Food-water consumption and body weight of the rats were monitored during the experiments. After the seven-day infusion, the rats were decapitated and serum TSH, fT4 and fT3 levels were determined with ELISA on rat blood samples. Also, TRH gene expression levels from the hypothalamus tissues and PGC-1α and UCP1 expression levels from WAT and BAT were determined by real-time PCR. It was determined that icv spexin infusion reduced daily food consumption and body weight without leading to a significant change in water consumption (p < 0.05). Icv spexin infusion significantly decreased serum TSH, and increased fT4 and fT3 levels when compared to control and sham groups (p < 0.05). Moreover, icv spexin infusion increased the TRH expressions in the hypothalamus tissues and PGC-1α UCP1 in the WAT and BAT (p < 0.05). Icv Spexin infusion may have effects on food consumption and body weight as well as, thyroid hormones and energy metabolism.


[Staphylococcal induction of suppressors of macrophage phagocytic activity].
During experimental infection caused by S. aureus, strain Smith, the formation of suppressors of the phagocytic activity of macrophages was induced in the peritoneal cavity and the spleen of intact and infected mice. Thus, in the cultivation of macrophages of the infected mice together with nonadhering cells of the peritoneal exudate of the infected animals the phagocytic index was 0.75 +/- 0.09; in the presence of splenocytes of the infected mice the phagocytic index for macrophages of the intact and infected animals was 0.64 +/- 0.12 and 0.89 +/- 0.04, respectively. Splenocytes of the intact mice, when cultivated together with macrophages of the infected mice, enhanced phagocytic activity during the first hours of cultivation and suppressed it after prolonged cultivation (12 hours); the phagocytic index was 1.37 +/- 0.18 and 0.82 +/- 0.03, respectively.


Systems biology and personalized medicine: a network approach to human disease.
Human diseases have historically been classified on the basis of their end-organ manifestations, using a traditional clinicopathological approach dating to the 19th century. With the advent of rigorous molecular methodologies at the end of the 20th century, many specific disease determinants were identified and more targeted therapeutic strategies developed. Although the conventional reductionist approach underlying these strategies for understanding disease served us well in the pregenomic era, it hampers our understanding of the complex molecular networks within which disease develops that are increasingly manifest in the current era. This article presents a novel, holistic method for classifying human diseases that can serve as a template for understanding disease pathobiology, prognosis, and treatment.


Logarithmic phase Escherichia coli K1 efficiently avoids serum killing by promoting C4bp-mediated C3b and C4b degradation.
Meningitis caused by Escherichia coli K1 is a serious illness in neonates with neurological sequelae in up to 50% of survivors. A high degree of bacteremia is required for E. coli K1 to cross the blood-brain barrier, which suggests that the bacterium must evade the host defence mechanisms and survive in the bloodstream. We previously showed that outer membrane protein A (OmpA) of E. coli binds C4b-binding protein (C4bp), an inhibitor of complement activation via the classical pathway. Nevertheless, the exact mechanism by which E. coli K1 survives in serum remains elusive. Here, we demonstrate that log phase (LP) OmpA+ E. coli K1 avoids serum bactericidal activity more effectively than postexponential phase bacteria. OmpA- E. coli cannot survive in serum grown to either phase. The increased serum resistance of LP OmpA+ E. coli is the result of increased binding of C4bp, with a concomitant decrease in the deposition of C3b and the downstream complement proteins responsible for the formation of the membrane attack complex. C4bp bound to E. coli K1 acts as a cofactor to factor I in the cleavage of both C3b and C4b, which shuts down the ensuing complement cascade. Accordingly, a peptide corresponding to the complement control protein domain 3 of C4bp sequence, was able to compete with C4bp binding to OmpA and cause increased deposition of C3b. Thus, binding of C4bp appears to be responsible for survival of E. coli K1 in human serum.


[Nonmyeloablative allogeneic stem cell transplantation for a 70-year-old woman with relapsed acute myelogenous leukemia].
We describe a 70-year-old woman with acute myelogenous leukemia with t(8;21) in the first relapse who underwent nonmyeloablative transplantation with conditioning of fludarabine and low-dose total body irradiation (2Gy). Myelosuppression was very mild, and the patient developed transient grade I renal and hepatic toxicities. Complete chimerism was achieved on day 120. The level of the AML1/MTG8 fusion gene in bone marrow decreased to an undetectable level on day 56 and the patient is alive and in complete remission with a follow-up at day 450. This transplant regimen might be well tolerated even by the elderly patients and bring a durable remission.


Effects of buckwheat sprouts on plasma and hepatic parameters in type 2 diabetic db/db mice.
We examined the effects of buckwheat sprouts (BS) (Fagopyrum esculentum Moench) on lipid and carbohydrate metabolism and on in vivo oxidative stress in type 2 diabetic mice. Mice (C57BL/KsJ-lepr(db)/lepr(db), db/db) were fed a diet containing 0%, 5%, or 10% BS based on AIN-93G for 21 d. Plasma parameters, such as total cholesterol, arteriosclerotic index, thiobarbituric acid reactive substances (TBARS), and the HbA1c concentration of whole blood in the diabetic BS-fed groups were lower than those in the diabetic control (AIN-93G) group. Concentrations of hepatic parameters, such as lipids, total cholesterol, triglyceride, and TBARS levels in BS-fed groups, were lower than those in the diabetic control group. Although gene expressions of the hepatic lipid regulation enzymes such as 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoAR) and cholesterol 7α-hydroxylase (CYP7A1) in diabetic BS-fed groups were higher than in the diabetic control group, the elevation of mRNA level of CYP7A1 was greater than that of HMG-CoAR. In addition, concentration of bile acids in feces was higher in the diabetic BS-fed groups than in the diabetic control group. These results suggest that BS have various in vivo activities in relation to antidiabetic effects in type 2 diabetic mice, especially for improvement in lipid metabolism. It was deduced that excretion of bile acids in feces by feeding the BS diet would contribute to the suppression of the cholesterol concentration in the plasma and liver tissues of mice.


Genome annotation errors in pathway databases due to semantic ambiguity in partial EC numbers.
We report on a new type of systematic annotation error in genome and pathway databases that results from the misinterpretation of partial Enzyme Commission (EC) numbers such as '1.1.1.-'. This error results in the assignment of genes annotated with a partial EC number to many or all biochemical reactions that are annotated with the same partial EC number. That inference is faulty because of the ambiguous nature of partial EC numbers. We have observed this type of error in multiple databases, including KEGG, VIMSS and IMG, all of which assign genes to KEGG pathways. The Escherichia coli subset of the KEGG database exhibits this error for 6.8% of its gene-reaction assignments. For example, KEGG contains 17 reactions that are annotated with EC 1.1.1.-. A group of three E.coli genes, b1580 [putative dehydrogenase, NAD(P)-binding, starvation-sensing protein], b3787 (UDP-N-acetyl-D-mannosaminuronic acid dehydrogenase) and b0207 (2,5-diketo-D-gluconate reductase B), is assigned to 15 of those reactions, despite experimental evidence indicating different single functions for two of the three genes. Furthermore, the databases (DBs) are internally inconsistent in that the description of gene functions for genes with partial EC numbers is inconsistent with the activities implied by reactions to which the genes were assigned. We infer that these inconsistencies result from the processing used to match gene products to reactions within KEGG's metabolic pathways. These errors affect scientists who use these DBs as online encyclopedias and they affect bioinformaticists who use these DBs to train and validate newly developed algorithms.


I.Q.H., information and quality healthcare: improving the care of patients with acute myocardial infarction and congestive heart failure.
Acute myocardial infarction and congestive heart failure are prevalent conditions in Mississippi associated with significant mortality and morbidity. It is critically important that physicians and hospital staffs work together to implement system and process changes that will facilitate the appropriate, timely evaluation and use of indicated therapies in both AMI and CHF patients. Change, while never easy, can be beneficial when properly motivated, designed and implemented. Physicians can and do make a difference not only in the quality of care given but also in the quality of life lived by their patients. I.Q.H. is encouraging all Mississippi physicians and healthcare facilities to examine their treatment processes for AMI and CHF.


Association of SERPINA9 gene variants with carotid artery atherosclerosis: the Atherosclerosis Risk in Communities (ARIC) Carotid MRI Study.
The SNP rs11628722 in the SERPINA9 gene was previously associated with incident ischemic stroke in the Atherosclerosis Risk in Communities (ARIC) study. Centerin, the protein encoded by SERPINA9, is involved in maturation and maintenance of naïve B cells, which play a role in atherogenesis. We investigated whether 21 tag SNPs in the SERPINA9 gene are associated with features of carotid artery atherosclerotic plaque measured by magnetic resonance imaging (MRI). Carotid MRI data were obtained from 1,282 European Americans and 341 African Americans of the ARIC Carotid MRI study, which recruited participants from ARIC by a stratified sampling plan that over-sampled participants with carotid intima-media thickening. Five MRI measures, focused on carotid wall volume, wall thickness, and lipid core, were analyzed. Genetic associations between the MRI measurements and each of the 21 SNPs were analyzed in linear regression models with adjustment for sample weights and traditional risk factors. Rs11628722 was tested a priori. In African Americans, rs11628722 was significantly associated with carotid wall volume (p < 0.05). Among the other 20 SNPs, adjusted for multiple testing, rs4905204, which encodes an Ala to Val amino acid change, was significantly associated with maximum wall thickness (p < 0.000625) and suggestively associated with total wall volume (p < 0.0026) in European Americans. In conclusion, SNPs in the SERPINA9 gene showed race-specific associations with characteristics of carotid atherosclerotic plaques. Replications in other populations are needed to validate findings of this study and to establish the SERPINA9 gene as a candidate in the etiology of carotid atherosclerosis.


Pretranslational regulation of type 2 deiodinase.
Type 2 deiodinase (D2) is a highly potent selenoenzyme that catalyzes the first step of thyroid hormone action and its expression is under close, multilevel control. D2 expression is tissue specific and can be regulated by transcriptional and posttranscriptional mechanisms. There is now compelling evidence that D2 is critically important in triiodothyronine (T3) homeostasis as well as in several biologic processes in which thyroid hormone is involved. A host of factors are known to influence dio2 mRNA including the transcription factors that regulate the dio2 gene in different cell types. In particular, cyclic adenosine monophosphate (cAMP) and two homeodomain- containing proteins are relevant for its defined and highly dynamic expression pattern. Single nucleotide polymorphisms of the dio2 gene and other pre-translational events such as alternative splicing can potentially modulate D2 expression and ultimately T(3) generation. Given the wealth of data accumulated over the past two decades, we have attempted in this review to provide a comprehensive update on the pretranslational regulation of D2.


Women's knowledge, attitude and practice towards menopause and hormone replacement therapy: a facility based study in Al-Ain, United Arab Emirates.
Hormone replacement therapy (HRT) is an effective treatment for menopausal symptoms like vasomotor symptoms, sleep disturbances, mood alteration, depression, urinary tract infection, vaginal atrophy and increased health risks for osteoporosis, cardiovascular diseases and loss of cognitive function. This study was conducted to determine knowledge, attitude and practice toward menopause among women in UAE. A clinic-based cross-sectional study was carried out among women of age 40 and above. Study subjects were recruited from four Primary Health Care centres in Al Ain city. The participants were administered a questionnaire in Arabic and English, which included 33 items; socio-demographic variables, and questions related to knowledge, attitude and practices regarding menopause and HRT. Out of 177 study subjected selected, 150 (85%) completed the survey. Almost half of the participants (51%) had already experienced menopause. A substantial number of women had poor know knowledge about menopause (67%) and HRT (73%). Sixty percent of women had positive attitude towards menopause. Of the fifty three percent of women with symptoms, 35% of them did not use anything to relieve their symptoms. Knowledge about menopause varied significantly (p<0.05) with the level of education and nationality. The association between reported symptoms and attitude towards menopause and HRT was found to be statistically significant. Women with reported symptoms that were bothersome had positive attitude towards HRT uptake. The study indicated that there is poor knowledge about menopause and HRT among the participants. Level of knowledge was associated with the level of education. There was a positive attitude towards menopause, with women suffering the most from menopausal symptoms showing positive attitude towards HRT.


Apelin-13 inhibits gastric motility through vagal cholinergic pathway in rats.
The expression of apelin and its receptors (APJ) in central autonomic networks suggests that apelin may regulate gastrointestinal motor functions. In rodents, central administration of apelin-13 has been shown to inhibit gastric emptying; however, the mechanisms involved remain to be determined. Using male adult Sprague-Dawley rats, the aims of the present study were 1) to determine the expression of APJ receptor in the dorsal vagal complex (DVC), 2) to assess the effects of central application of apelin-13 into the DVC on gastric tone and motility, and 3) to investigate the neuronal pathways responsible for apelin-induced alterations. APJ receptor immunoreactivity was detected in gastric-projecting and choline acetyltransferase-positive neurons of the DVC. Microinjection of apelin-13 into the DVC significantly decreased gastric tone and motility in both corpus and antrum. The apelin-induced reduction in gastric tone and motility was prevented by surgical vagotomy or fourth ventricular application of the APJ receptor antagonist, [Ala13]apelin-13 (F13A). Systemic administration of the muscarinic receptor antagonist atropine, but not the nitric oxide synthase inhibitor nitro-l-arginine methyl ester (l-NAME), abolished the apelin-induced inhibitory responses. The present results indicate a central modulatory role of apelin in the vagal neurocircuitry that controls gastric motor functions via withdrawal of the tonically active cholinergic pathway. NEW & NOTEWORTHY This is the first study investigating the effects induced by brain stem application of apelin-13 while monitoring gastric tone and motility in rats. We have found that gastric-projecting neurons of the dorsal vagal complex express apelin receptors (APJ), which mediate the inhibitory actions of apelin-13. The inhibitory effects of apelin were abolished by systemic preadministration of atropine, but not nitro-l-arginine methyl ester (l-NAME). Apelin seems to modulate gastric motility via withdrawal of the tonically active vagal cholinergic pathway.


Cashew consumption reduces total and LDL cholesterol: a randomized, crossover, controlled-feeding trial.
Background: Cashews are the third most-consumed tree nut in the United States and are abundant with monounsaturated fatty acids and polyunsaturated fatty acids, which are associated with reduced cardiovascular disease risk. Although a qualified Food and Drug Administration health claim exists for nuts and heart health, cashews have been exempt from its use because cashews exceed the disqualifying amount of saturated fatty acids. Approximately one-third of the saturated fat in cashews is stearic acid, which is relatively neutral on blood lipids, thereby suggesting that cashews could have effects that are similar to those of other nuts. However, clinical data on cashews and blood lipids have been limited.Objective: We investigated the effect of reasonable intakes of cashews on serum lipids in adults with or at risk of high LDL cholesterol.Design: In a randomized, crossover, isocaloric, controlled-feeding study, 51 men and women (aged 21-73 y) with a median LDL-cholesterol concentration of 159 mg/dL (95% CI: 146, 165 mg/dL) at screening consumed typical American diets with cashews (28-64 g/d; 50% of kilocalories from carbohydrate, 18% of kilocalories from protein, and 32% of kilocalories from total fat) or potato chips (control; 54% of kilocalories from carbohydrate, 18% of kilocalories from protein, and 29% of kilocalories from total fat) for 28 d with a ≥2-wk washout period.Results: Consumption of the cashew diet resulted in a significantly greater median change from baseline (compared with the control, all P < 0.05) in total cholesterol [-3.9% (95% CI: -9.3%, 1.7%) compared with 0.8% (95% CI: -1.5%, 4.5%), respectively], LDL cholesterol [-4.8% (95% CI: -12.6%, 3.1%) compared with 1.2% (95% CI: -2.3%, 7.8%), respectively], non-HDL cholesterol [-5.3% (95% CI: -8.6%, 2.1%) compared with 1.7% (95% CI: -0.9%, 5.6%), respectively], and the total-cholesterol:HDL-cholesterol ratio [-0.0% (95% CI: -4.3%, 4.8%) compared with 3.4% (95% CI: 0.6%, 5.2%), respectively]. There were no significant differences between diets for HDL cholesterol and triglyceride.Conclusions: In comparison with a control diet, the incorporation of cashews into typical American diets decreases total cholesterol and LDL cholesterol. Results from this study provide support that the daily consumption of cashews, when substituted for a high-carbohydrate snack, may be a simple dietary strategy to help manage total cholesterol and LDL cholesterol. This study was registered at clinicaltrials.gov as NCT02769741.


A Mixed-Methods Approach to Understanding Variation in Social Support Requirements and Implications for Access to Transplantation in the United States.
Social support is a key component of transplantation evaluation in the United States. Social support definitions and evaluation procedures require examination to achieve clear, consistent implementation. We surveyed psychosocial clinicians from the Society for Transplant Social Workers and American Society of Transplant Surgeons about their definitions and evaluation procedures for using social support to determine transplant eligibility. Bivariate statistical analysis was used for quantitative data and content analysis for qualitative data. Among 276 psychosocial clinicians (50.2% response rate), 92% had ruled out patients from transplantation due to inadequate support. Social support definitions varied significantly: 10% of respondents indicated their center lacked a definition. Key domains of social support included informational, emotional, instrumental, motivational, paid support, and the patient's importance to others. Almost half of clinicians (47%) rarely or never requested second opinions when excluding patients due to social support. Confidence and perceived clarity and consistency in center guidelines were significantly associated with informing patients when support contributed to negative wait-listing decisions (P = .001). Clinicians who excluded fewer patients because of social support offered significantly more supportive health care (P = .02). Clearer definitions and more supportive care may reduce the number of patients excluded from transplant candidacy due to inadequate social support.


Guiding Oligodendrocyte Precursor Cell Maturation With Urokinase Plasminogen Activator-Degradable Elastin-like Protein Hydrogels.
Demyelinating injuries and diseases, like multiple sclerosis, affect millions of people worldwide. Oligodendrocyte precursor cells (OPCs) have the potential to repair demyelinated tissues because they can both self-renew and differentiate into oligodendrocytes (OLs), the myelin producing cells of the central nervous system (CNS). Cell-matrix interactions impact OPC differentiation into OLs, but the process is not fully understood. Biomaterial hydrogel systems help to elucidate cell-matrix interactions because they can mimic specific properties of native CNS tissues in an in vitro setting. We investigated whether OPC maturation into OLs is influenced by interacting with a urokinase plasminogen activator (uPA) degradable extracellular matrix (ECM). uPA is a proteolytic enzyme that is transiently upregulated in the developing rat brain, with peak uPA expression correlating with an increase in myelin production in vivo. OPC-like cells isolated through the Mosaic Analysis with Double Marker technique (MADM OPCs) produced low-molecular-weight uPA in culture. MADM OPCs were encapsulated into two otherwise similar elastin-like protein (ELP) hydrogel systems: one that was uPA degradable and one that was nondegradable. Encapsulated MADM OPCs had similar viability, proliferation, and metabolic activity in uPA degradable and nondegradable ELP hydrogels. Expression of OPC maturation-associated genes, however, indicated that uPA degradable ELP hydrogels promoted MADM OPC maturation although not sufficiently for these cells to differentiate into OLs.


What is the best option to manage the bedside teaching for Neurology Clerkship -- Demonstration, Simulation or WeChat teaching?
This article was migrated. The article was marked as recommended. Background: Neurological clerkship is an important but challenging part of the neurology curriculum, and bedside teaching is essential for clerks to integrate complex theories and skills into practice. Objective: This study aimed to investigate the three bedside teaching methods as modified bedside demonstration, simulation via standard patients as well as WeChat-assisted teaching during neurological clerkship, in order to identify the optimal method. Design: The4 th-year medical students were enrolled during their neurological clerkship. Bedside teaching on topics of acute ischemic stroke, acute myelitis and myasthenia gravis were delivered in a random order of demonstration, simulation and WeChat-assisted teaching. A questionnaire was assigned to each participant at the end of the two-week clerkship to rank the three methods based on their general impression, as well as detailed assessment of clinical abilities and attitudes. Results: A total of 112 clerks were enrolled and 98 were eligible for analysis. For both general and overall ranking, simulation was the most approved bedside teaching method while WeChat-assisted teaching took the least approval among the three. A majority of participants preferred simulation because of the significant improvement on interpretation of diseases, interest in neurology, diagnostic skills, clinical skills, communication skills, empathy and protection of privacy (P<0.05). Demonstration was considered to benefit performance in examination (P=0.009). The ranking of the three methods revealed different consistency between general impression and detailed assessment. More participants tended to underestimate themselves in simulation but to overestimate themselves in WeChat-assisted teaching (P=0.000). Conclusions: Simulation outweigh WeChat-assisted teaching and demonstration by promoting clinical skills, as well as inspiring students' academic interest, compassion and empathy in both the general ranking and the overall ranking. Clerks were tended to underestimate their clinical competence in simulation but overestimate themselves in WeChat-assisted teaching.


A longitudinal study of knee pain in older men: Concord Health and Ageing in Men Project.
chronic knee pain is still considered a fairly benign disease by many, an 'unavoidable' consequence of ageing. This passive acceptance may be unnecessarily exposing older people to disability and serious co-morbidity. The aim of this study was to determine the disease burden associated with chronic knee pain and the role of knee extensor strength as a modifiable risk factor. a longitudinal cohort study with 2-year follow-up conducted among 1,587 community-dwelling men aged 70 years and over, 637 (40%) reported chronic knee pain. Of the 950 (60%) men without knee pain at baseline, 768 (81%) returned for the follow-up assessment with 150 (20%) reporting incident chronic knee pain. knee pain was significantly associated with marked mobility disability [odds ratio (OR) 2.38; 95% confidence interval (CI) 1.74-3.29], falls (OR: 1.31; 95% CI: 1.01-1.70) and having four or more co-morbidity (OR: 1.63; 95% CI: 1.16-2.30) as well as reduced knee extensor strength and mass (dual X-ray absorptiometry). Men with incident knee pain at the 2-year follow-up assessment demonstrated greater increases in these measures of disease burden and greater decreases in muscle strength and mass, compared with those without incident chronic knee pain. Obesity, high co-morbidity burden, back pain, higher levels of physical activity or low knee extensor strength were all significant risk factors for incident knee pain. prevention of chronic knee pain may reduce a considerable burden of mobility disability and increased risk of serious co-morbidity among older men.


Independent evolution of human immunodeficiency virus (HIV) drug resistance mutations in diverse areas of the brain in HIV-infected patients, with and without dementia, on antiretroviral treatment.
AIDS dementia complex (ADC) in human immunodeficiency virus (HIV)-infected patients continues to be a problem in the era of highly active antiretroviral therapy (HAART). A better understanding of the drug resistance mutation patterns that emerge in the central nervous system (CNS) during HAART is of paramount importance as these differences in drug resistance mutations may explain underlying reasons for poor penetration of antiretroviral drugs into the CNS and suboptimal concentrations of the drugs that may reside in the brains of HIV-infected individuals during therapy. Thus, we provide a detailed analysis of HIV type 1 (HIV-1) protease and reverse transcriptase (RT) genes derived from different regions of the brains of 20 HIV-1-infected patients (5 without ADC, 2 with probable ADC, and 13 with various stages of ADC) on antiretroviral therapy. We show the compartmentalization and independent evolution of both primary and secondary drug resistance mutations to both RT and protease inhibitors in diverse regions of the CNS of HIV-infected patients, with and without dementia, on antiretroviral therapy. Our results suggest that the independent evolution of drug resistance mutations in diverse areas of the CNS may emerge as a consequence of incomplete suppression of HIV, probably related to suboptimal drug levels in the CNS and drug selection pressure. The emergence of resistant virus in the CNS may have considerable influence on the outcome of neurologic disease and also the reseeding of HIV in the systemic circulation upon failure of therapy.


Identification of an Optimal Cut-off for Drain Fluid Amylase on Postoperative Day 1 for Predicting Clinically Relevant Fistula After Distal Pancreatectomy: A Multi-institutional Analysis and External Validation.
The aim of this study was to investigate the relationship between drain fluid amylase value on the first postoperative day (DFA1) and clinically relevant fistula (CR-POPF) after distal pancreatectomy (DP), and to identify the cut-off of DFA1 that optimizes CR-POPF prediction. DFA1 is a well-recognized predictor of CR-POPF after pancreatoduodenectomy, but its role in DP is largely unexplored. DFA1 levels were correlated with CR-POPF in 2 independent multi-institutional sets of DP patients: developmental (n = 338; years 2012 to 2017) and validation cohort (n = 166; years 2006 to 2016). Cut-off choice was based on Youden index calculation, and its ability to predict CR-POPF occurrence was tested in a multivariable regression model adjusted for clinical, demographic, operative, and pathological variables. In the developmental set, median DFA1 was 1745 U/L and the CR-POPF rate was 21.9%. DFA1 correlated with CR-POPF with an area under the curve of 0.737 (P < 0.001). A DFA1 of 2000 U/L had the highest Youden index, with 74.3% sensitivity and 62.1% specificity. Patients in the validation cohort displayed different demographic and operative characteristics, lower values of DFA1 (784.5 U/L, P < 0.001), and reduced CR-POPF rate (10.2%, P < 0.001). However, a DFA1 of 2000 U/L had the highest Youden index in this cohort as well, with 64.7% sensitivity and 75.8% specificity. At multivariable analysis, DFA1 ≥2000 U/L was the only factor significantly associated with CR-POPF in both cohorts. A DFA1 of 2000 U/L optimizes CR-POPF prediction after DP. These results provide the substrate to define best practices and improve outcomes for patients receiving DP.


Prevalence of and risk factors for hepatitis B virus infection among street-recruited young injection and non-injection heroin users in Barcelona, Madrid and Seville.
To evaluate the prevalence of hepatitis B virus (HBV) and associated factors in 949 heroin users (HU): injectors (IHUs) and non-injectors (NIHUs). Cross-sectional study; structured questionnaire administered by computer-assisted personal interviewing and audio computer-assisted self-interviewing; dry blood samples analysed for the hepatitis B core antigen and hepatitis B surface antigen; bivariate analysis and logistic regression. The prevalence of infection was significantly higher in IHUs (22.5%) than in NIHUs (7.4%) in the three cities. In the logistic analysis of male IHUs, infection was found to be associated with living in Seville, age over 25, foreign nationality, having had a sexual partner who traded sex, hepatitis C virus infection, and having injected for more than 5 years. In female IHUs, HBV infection was associated with age over 25, having injected as the first main route of administration, and having begun to inject before 18 years of age. In NIHUs, the associated factors were female gender, foreign nationality and having been tattooed. In young IHUs, the prevalence of HBV infection remains four times higher than in the general population of the same age group. The vaccination strategy urgently needs to be reinforced and redesigned to achieve acceptable control of the HBV infection in the most vulnerable groups, with special attention to immigrants.


A three-parameter analytical model for the acoustical properties of porous media.
Many models for the prediction of the acoustical properties of porous media require non-acoustical parameters few of which are directly measurable. One popular prediction model by Johnson, Champoux, Allard, and Lafarge [J. Appl. Phys. 70(4), 1975-1979 (1991)] (459 citations, Scopus, April 2019) requires six non-acoustical parameters. This paper proves that the use of more than three parameters in the Johnson-Champoux-Allard-Lafarge model is not necessary at all. Here the authors present theoretical and experimental evidence that the acoustical impedance of a range of porous media with pore size distribution close to log-normal (granular, fibrous, and foams) can be predicted through the knowledge of the porosity, median pore size, and standard deviation in the pore size only. A unique feature of this paper is that it effectively halves the number of parameters required to predict the acoustical properties of porous media very accurately. The significance of this paper is that it proposes an unambiguous relationship between the pore microstructure and key acoustical properties of porous media with log-normal pore size distribution. This unique model is well suited for using acoustical data for measuring and inverting key non-acoustical properties of a wider range of porous media used in a range of applications which are not necessarily acoustic.


Pattern of breast cancer in Saudi females in eastern province of Saudi Arabia.
We present our retrospective analysis of malignant breast tumours seen at King Fahd University Hospital between 1982 to 1987. 1,658 Saudi nationals were admitted with different malignant conditions, out of this 69 (4.1%) females suffered from breast cancer. Majority of the patients were between the age 31-50 years and half of them presented within the first 6 months of the symptoms. All the patients were married, multiparous and had breast fed their new born. Our study suggests that the incidence of breast cancer among Saudi women is low, multiparous and breast feeding in no way gives any protection to the patients and ductal carcinoma remains the commonest histological type of breast tumour.


Salinity tolerance in Australian wild Oryza species varies widely and matches that observed in O. sativa.
Soil salinity is widespread in rice-producing areas globally, restricting both vegetative growth and grain yield. Attempts to improve the salt tolerance of Asian rice, Oryza sativa-the most salt sensitive of the major cereal crops-have met with limited success, due to the complexity of the trait and finite variation in salt responses among O. sativa lines. Naturally occurring variation among the more than 20 wild species of the Oryza genus has great potential to provide breeders with novel genes to improve resistance to salt. Here, through two distinct screening experiments, we investigated variation in salinity tolerance among accessions of two wild rice species endemic to Australia, O. meridionalis and O. australiensis, with O. sativa cultivars Pokkali and IR29 providing salt-tolerant and sensitive controls, respectively. Rice plants were grown on soil supplemented with field-relevant concentrations of NaCl (0, 40, 80, and 100 mM) for 30 d, a period sufficient to reveal differences in growth and physiological traits. Two complementary screening approaches were used: destructive phenotyping and high-throughput image-based phenotyping. All genotypes displayed clear responses to salt treatment. In the first experiment, both salt-tolerant Pokkali and an O. australiensis accession (Oa-VR) showed the least reduction in biomass accumulation, SES score and chlorophyll content in response to salinity. Average shoot Na+/K+ values of these plants were the lowest among the genotypes tested. In the second experiment, plant responses to different levels of salt stress were quantified over time based on projected shoot area calculated from visible red-green-blue (RGB) and fluorescence images. Pokkali grew significantly faster than the other genotypes. Pokkali and Oa-VR plants displayed the same absolute growth rate under 80 and 100 mM, while Oa-D grew significantly slower with the same treatments. Oa-VR showed substantially less inhibition of growth in response to salinity when compared with Oa-D. Senescence was seen in Oa-D after 30 d treatment with 40 mM NaCl, while the putatively salt-tolerant Oa-VR had only minor leaf damage, even at higher salt treatments, with less than a 40% increase in relative senescence at 100 mM NaCl compared to 120% for Oa-VR. The combination of our two screening experiments uncovered striking levels of salt tolerance diversity among the Australian wild rice accessions tested and enabled analysis of their growth responses to a range of salt levels. Our results validate image-based phenotyping as a valuable tool for quantitative measurement of plant responses to abiotic stresses. They also highlight the potential of exotic germplasm to provide new genetic variation for salinity tolerance in rice.


Acceleration of protein aggregation by amphiphilic peptides: transformation of supramolecular structure of the aggregates.
Protein self-assembly and aggregation represent a special tool in biomedicine and biotechnology to produce biological materials for a wide range of applications. The protein aggregates are very different morphologically, varying from soluble amorphous aggregates to highly ordered amyloid-like fibrils, the latter being associated with molecular structures able to perform specific functions in living systems. Fabrication of novel biomaterials resembling natural protein assemblies has awakened interest in identification of low-molecular-weight biogenic agents as regulators of transformation of aggregation-prone proteins into fibrillar structures. Short amphiphilic peptides can be considered for this role. Using dynamic light scattering, turbidimetry, fluorescence spectroscopy, and transmission electron microscopy (TEM), we have demonstrated that the Arg-Phe dipeptide dramatically accelerates the aggregation of a model protein, α-lactalbumin, to generate morphologically different structures. TEM revealed transformation of spherical particles observed in the control samples into branched chains of fibril-like nanostructures in the presence of the peptide, suggesting that amphiphilic peptides can induce changes in the physicochemical properties of a protein substrate (net charge, hydrophobicity, and tendency to β-structure formation) resulting in accumulation of peptide-protein complexes competent to self-assembly into supramolecular structures. A number of other short amphiphilic peptides have also been shown to accelerate the aggregation process, using alternative complementary protein substrates for identification of molecular recognition modules. Peptide-protein assemblies are suggested to play the role of building blocks for formation of supramolecular structures profoundly differing from those of the individual protein substrate in type, size, and shape.


Humanities for medical students: essential to their cultural competence and patient-engaged practices of care.
This article was migrated. The article was marked as recommended. Over the past 50 years, advances in medical technology have revolutionised the medical landscape. The ways in which patients, their families, and health professionals connect and interact together in the medical endeavour have also changed. At the same time as advances in medical technology resulted in tremendous gains for society, criticism began emerging that the patient as a whole person had been overshadowed by the disease the person had. The interface of medicine and the humanities concerns itself with our relationships with others, the ways in which we confront challenges to our mortality, how we understand human behaviour, and the meanings we give to situations within the medical context. In this paper we outline the genesis of a medical humanities programme at the University of Auckland, and how the programme has advanced over the past twenty years. The programme promotes important social aspects of medicine such as cultural competence and person-centred engaged care. It also encourages students to improve their academic and reflective writing skills. We discuss how one course within the programme promotes student cultural awareness of - and responsiveness to - Maori people and Deaf people. Specific attention is paid to current leading pedagogy, as well as how the use of space and language contribute to student learning. We conclude that medical humanities remains an essential and valued element in medical curricula.


Effects of time, soil organic matter, and iron oxides on the relative retention and redistribution of lead, cadmium, and copper on soils.
In order to predict the bioavailability of toxic metals in soils undergoing degradation of organic matter (OM) and iron oxides (IOs), it is vital to understand the roles of these soil components in relation to metal retention and redistribution with time. In this present work, batch competitive sorptions of Pb(II), Cu(II), and Cd(II) were investigated between 1 and 90 days. Results showed that competition affected Cd(II) sorption more than Cu(II) and Pb(II). The sorption followed the trend Pb(II) > > Cu(II) > Cd(II), irrespective of aging, and this high preference for Pb(II) ions in soils reduced with time. Removal of OM led to reduction in distribution coefficient (K d) values of ≈33% for all cations within the first day. However, K d increased nearly 100% after 7 days and over 1000% after 90-day period. The enhanced K d values indicated that sorptions occurred on the long run on surfaces which were masked by OM. Removal of IO caused selective increases in the K d values, but this was dependent on the dominant soil constituent(s) in the absence of IO. The K d values of the IO-degraded samples nearly remained constant irrespective of aging indicating that sorptions on soil components other than the IO are nearly instantaneous while iron oxides played greater role than other constituents with time. Hence, in the soils studied, organic matter content determines the immediate relative metal retention while iron oxides determine the redistribution of metals with time.


Characterization of the influences of morphology on the intrinsic properties of perovskite films by temperature-dependent and time-resolved spectroscopies.
Organic-inorganic halide perovskites have attracted enormous attention owing to their promising application in photovoltaic devices. The morphology of the perovskites is the key to driving the performance of perovskite devices, which necessitates a systematic study. In this work, two typical morphologies, i.e., flake and cube, of perovskite films are fabricated, and the temperature-dependent optical absorption and photoluminescence properties of the two types of perovskite film are systematically investigated. From the temperature-dependent spectra, both exciton and phase transition temperatures of the flake film are found to be about 10 K lower than those of the cube one. Meanwhile, the influences of the morphology on the exciton binding energy, optical phonon energy and polaron binding energy are quantitatively characterized. The exciton binding of the flake film is nearly three times smaller than that of the cube one, while the phonon coupling energy and the polaron binding energy of the former are about 5 meV and 2 meV larger than those of the latter. Furthermore, the results of photoluminescence lifetime and charge separation efficiency further reveal that the charge carrier kinetics in the two kinds of perovskite films is significantly different. The current study provides a theoretical framework to understand the fundamental physics of perovskites and to promote the design and enhancement of active materials for improved optoelectronic devices.


Passive multivariable temperature and conductivity RFID sensors for single-use biopharmaceutical manufacturing components.
Single-use biopharmaceutical manufacturing requires monitoring of critical manufacturing parameters. We have developed an approach for passive radio-frequency identification (RFID)-based sensing that converts ubiquitous passive 13.56 MHz RFID tags into inductively coupled sensors. We combine several measured parameters from the resonant sensor antenna with multivariate data analysis and deliver unique capability of multiparameter sensing and rejection of environmental interferences with a single sensor. We demonstrate here the integration of these RFID sensors into single-use biopharmaceutical manufacturing components. We have tested these sensors for over 500 h for measurements of temperature and solution conductivity with the accuracy of 0.1°C (32-48°C range) and accuracy of 0.3-2.9 mS/cm (0.5-230 mS/cm range). We further demonstrate simultaneous temperature and conductivity measurements with an individual RFID sensor with the accuracy of 0.2°C (5-60°C range) and accuracy of 0.9 mS/cm (0.5-183 mS/cm range). Developed RFID sensors provide several important features previously unavailable from other single-use sensing technologies such as the same sensor platform for measurements of physical, chemical, and biological parameters; multi-parameter monitoring with individual sensors; and simultaneous digital identification.


Psychodermatology: a guide to understanding common psychocutaneous disorders.
This review focuses on classification and description of and current treatment recommendations for psychocutaneous disorders. Medication side effects of both psychotropic and dermatologic drugs are also considered. A search of the literature from 1951 to 2004 was performed using the MEDLINE search engine. English-language articles were identified using the following search terms: skin and psyche, psychiatry and dermatology, mind and skin, psychocutaneous, and stress and skin. The psychotropic agents most frequently used in patients with psychocutaneous disorders are those that target anxiety, depression, and psychosis. Psychiatric side effects of dermatologic drugs can be significant but can occur less frequently than the cutaneous side effects of psychiatric medications. In a majority of patients presenting to dermatologists, effective management of skin conditions requires consideration of associated psychosocial factors. For some dermatologic conditions, there are specific demographic and personality features that commonly associate with disease onset or exacerbation. More than just a cosmetic disfigurement, dermatologic disorders are associated with a variety of psychopathologic problems that can affect the patient, his or her family, and society together. Increased understanding of biopsychosocial approaches and liaison among primary care physicians, psychiatrists, and dermatologists could be very useful and highly beneficial.


Local anaesthetic refinement of pentobarbital euthanasia reduces abdominal writhing without affecting immunohistochemical endpoints in rats.
Sodium pentobarbital is a commonly used agent for euthanizing laboratory rats, however its high pH can cause abdominal discomfort after intraperitoneal injection. Previous studies suggest that the addition of a local anaesthetic may alleviate this discomfort, but the practice has not been widely adopted. We examined the effect of combining lidocaine with pentobarbital on abdominal writhing, defecation, ultrasonic vocalizations, the rat grimace scale and immunohistochemical staining for c-Fos in the nucleus accumbens and basolateral amygdala of the brain. We also compared the amount of abdominal writhing following intraperitoneal administration of pentobarbital-lidocaine with that of pentobarbital-bupivacaine. Our results show that lidocaine reduces abdominal writhing and defecation without affecting immunohistochemistry for c-Fos or latency to loss of posture. However, scores on the rat grimace scale were low in both situations and almost no ultrasonic vocalizations were recorded. Additionally, we found that the amount of abdominal writhing was not significantly different when bupivacaine was used rather than lidocaine. Our results suggest that pentobarbital-induced euthanasia can be refined with the addition of lidocaine or other local anaesthetics.


miR-29a Regulates the Proliferation and Migration of Human Arterial Smooth Muscle Cells in Arteriosclerosis Obliterans of the Lower Extremities.
The molecular mechanisms underlying the contribution of human arterial smooth muscle cells (HASMCs), one of the most important components of the arterial wall, to the pathogenesis of arteriosclerosis obliterans (ASO) remain elusive. The expression levels of miR-29a in arterial walls were analyzed via real-time-polymerase chain reaction. An ASO cell model was established to investigate the expression of miR-29a on HASMCs. The interaction between miR-29a and platelet-derived growth factor receptor B (PDGFRB) was detected by luciferase reporter assay, and the alteration of the expression of PDGFRB was determined in platelet-derived growth factor‑BB (PDGF-BB)-stimulated HASMCs transfected with miR-NC, miR-29a mimics, and miR-29a inhibitors. Further, HASMCs cell proliferation was investigated by cell counting kit-8 and EdU assays, and cell migrations were evaluated by Transwell and wound closure assays. The expression of miR-29a was remarkably downregulated in the arterial walls of ASO patients compared with normal arterial walls. Furthermore, expression of miR-29a in HASMCs under PDGF-BB stimulation was lower than vehicle control. PDGFRB was identified as a target of miR-29a in HASMCs, and miR-29a inhibited the proliferation and migration in PDGF-BB-induced HASMCs, via regulating the expression of PDGFRB. This study showed that miR-29a is downregulated in the arterial wall of ASO patients, as well as in the PDGF-BB-stimulated HASMCs. This alteration of miR-29a could upregulate target genes PDGFRB and inhibits the proliferation and migration of HASMCs. These findings discovered new mechanisms of ASO pathogenesis, and the miR-29a/PDGFRB axis could serve as potential therapy target of ASO.


Safety of losartan in hypertensive patients with thiazide-induced hyperuricemia.
Losartan, an angiotensin II receptor antagonist, has been shown to decrease serum uric acid and to increase urinary excretion of uric acid. To determine if this effect can increase the risk of acute urate nephropathy, 63 hypertensive patients with thiazide-induced asymptomatic hyperuricemia (serum uric acid 7.0 to 12.0 mg/dl) were randomized double-blind to losartan 50 mg every day (q.d.), losartan 50 mg plus hydrochlorothiazide (HCTZ) 50 mg q.d., HCTZ 50 mg q.d., or placebo for three weeks. To potentiate the risk of crystal formation, patients received a 2 g/kg protein diet one day prior to each clinic visit on days 0 (baseline), 1, 7, and 21. Adverse events typically associated with acute urate nephropathy, for example, flank pain, hematuria, or increased blood urea nitrogen/creatinine, were not reported. Uric acid excretion and urine pH increased four and six hours after losartan on day 1 compared with day 0. Dihydrogen urate, the primary risk factor for crystal formation, decreased at four and six hours on day 1 compared with day 0 associated with the concurrent rise in urine pH. Day 7 and 21 changes, compared with day 0, in uric acid excretion rate, urine pH, and dihydrogen urate with losartan were comparable to day 1 results but were not statistically significant. Serum uric acid was significantly reduced after 21 days of therapy with losartan. Losartan decreased serum uric acid and increased uric acid excretion without increasing urinary dihydrogen urate, the primary risk factor for acute urate nephropathy, during 21 days of dosing in hypertensive patients with thiazide-induced hyperuricemia.


Evidence-Based Utility of Adjunct Antioxidant Supplementation for the Prevention and Treatment of Dermatologic Diseases: A Comprehensive Systematic Review.
Skin conditions are a significant cause of fatal and nonfatal disease burdens globally, ranging from mild irritations to debilitating diseases. Oxidative stress, which is an imbalance between reactive oxygen species and the cells' ability to repair damage, is implicated in various skin diseases. Antioxidants have been studied for their potential benefits in dermatologic health, but the evidence is limited and conflicting. Herein, we conducted a systematic review of controlled trials, meta-analyses, and Cochrane review articles to evaluate the current evidence on the utility of antioxidant supplementation for adjunct prevention and treatment of skin disease and to provide a comprehensive assessment of their role in promoting dermatologic health. The Cochrane Library, PubMed, EMBASE, and Epistemonikos databases were queried. Eligibility criteria included (1) primary focus on nanoparticle utility for skin cancer; (2) includes measurable outcomes data with robust comparators; (3) includes a number of human subjects or cell-line types, where applicable; (4) English language; and (5) archived as full-text journal articles. A total of 55 articles met the eligibility criteria for the present review. Qualitative analysis revealed that topical and oral antioxidant supplementation has demonstrated preliminary efficacy in reducing sunburns, depigmentation, and photoaging. Dietary exogenous antioxidants (namely vitamins A, C, and E) have shown chemopreventive effects against skin cancer. Antioxidant supplementation has also shown efficacy in treating non-cancer dermatoses, including rosacea, psoriasis, atopic dermatitis, and acne vulgaris. While further studies are needed to validate these findings on a larger scale, antioxidant supplementation holds promise for improving skin health and preventing skin diseases.


Effect of Metabolic Adaptation by Voluntary Running Wheel Activity and Aldosterone Inhibition on Renal Function in Female Spontaneously Hypertensive Rats.
Metabolic effects of physical activity may be reno-protective in the context of hypertension, although exercise stresses kidneys. Aldosterone participates in renal disease in hypertension, but exercise affects the plasma concentration of aldosterone. This study was designed to evaluate whether physical activity and pharmacological treatment by aldosterone have additive effects on renal protection in hypertensive rats. Female spontaneously hypertensive rats (SHR) or normotensive Wistar rats performed voluntary running wheel activity alone or in combination with aldosterone blockade (spironolactone). The following groups were studied: young and pre-hypertensive SHR (n = 5 sedentary; n = 10 running wheels, mean body weight 129 g), 10-month-old Wistar rats (n = 6 sedentary; n = 6 running wheels, mean body weight 263 g), 10-month-old SHRs (n = 18 sedentary, mean body weight 224 g; n = 6 running wheels, mean body weight 272 g; n = 6 aldosterone, mean body weight 219 g; n = 6 aldosterone and running wheels, mean body weight 265 g). Another group of SHRs had free access to running wheels for 6 months and kept sedentary for the last 3 months (n = 6, mean body weight 240 g). Aldosterone was given for the last 4 months. SHRs from the running groups had free access to running wheels beginning at the age of 6 weeks. Renal function was analyzed by microalbuminuria (Alb/Cre), urinary secretion of kidney injury molecule-1 (uKim-1), and plasma blood urea nitrogen (BUN) concentration. Molecular adaptation of the kidney to hypertension and its modification by spironolactone and/or exercise were analyzed by real-time PCR, immunoblots, and histology. After six months of hypertension, rats had increased Alb/Cre and BUN but normal uKim-1. Voluntary free running activity normalized BUN but not Alb/Cre, whereas spironolactone reduced Alb/Cre but not BUN. Exercise constitutively increased renal expression of proprotein convertase subtilisin/kexin type 9 (PCSK9; mRNA and protein) and arginase-2 (mRNA). Spironolactone reduced these effects. uKim-1 increased in rats performing voluntary running wheel activity exercise irrespectively of blood pressure and aldosterone blockade. We observed independent but no additive effects of aldosterone blockade and physical activity on renal function and on molecules potentially affecting renal lipid metabolism.


A new predictive model for insulin-dependent diabetes mellitus susceptibility based on combinations of molecular HLA-DRB1 and HLA-DQB1 pockets.
With a view to establishing an accurate evaluation of the genetic predisposition to insulin-dependent type I diabetes (IDDM), we have built a model based on the characteristics of the relevant pockets of HLA-DR and -DQ molecules. Three independent populations were investigated. Group I and group II were Caucasoids, while group III was Japanese, including a total of 1,166 IDDM patients and 2,391 healthy controls. We formulate the hypothesis that suceptibility to IDDM is not only explained by the absence of Aspartate 57 (negative charge) from pocket 9 of DQB1 (P9DQ), but also by the presence of an electric charge (+/- vs. neutral), generated by residues 70, 71 and 74 in pockets 4 of DRB1 (P4DR) and DQB1 (P4DQ) molecules. The respective weight of each pocket, was evaluated in a multivariate analysis based on the logistic regression method. The 4 components (2 loci and 2 pockets) were systematically analysed in the computer model. It was clearly shown that the structural characteristics of pockets P9DQ-P4DR and, to a lesser degree that of P4DQ, account for IDDM predisposition. On applying the model to the whole international series, it appears that the highest risk concerns individuals with P9DQ non-Asp 57 and both the charged P4 of DRB1 and P4 of DQB1, conferring a 80% prediction of susceptibility. Conversely, P9DQ Asp and neutral P4DR and P4DQ give the lowest risk with a predictive value of 5%. This model of risk susceptibility prediction fits remarkably well with the observed distribution in a worldwide study. It allows a better evaluation of the respective role of HLA-DR and -DQ molecules as a major component of susceptibility to IDDM.


Does PEEP facilitate the resolution of extravascular lung water after experimental hydrostatic pulmonary oedema?
The effect of mechanical ventilation with positive end-expiratory pressure on the resolution of hydrostatic pulmonary oedema created by temporary left atrial balloon inflation was studied in mechanically ventilated dogs. Immediately after the hydrostatic process was terminated, by deflating the left atrial balloon, the animals were ventilated for 4 h with zero end-expiratory pressure (ZEEP, n = 6) or with a positive end-expiratory pressure (PEEP, n = 6) of 1.0 kPa (10 cmH2O). Gas exchange and extravascular lung water content (EVLW) with the double indicator dilution technique (dye/cold) were studied and gravimetric determination of lung water was made postmortem. EVLW decreased from 31.6 +/- 7.3 mean +/- SD ml.kg.1 during maximal oedema to 14.5 +/- 2.1 ml.kg.1 (p less than 0.001) 4 h after deflation of the left atrial balloon in dogs ventilated with ZEEP. The corresponding values in dogs ventilated with PEEP were a reduction in EVLW from 28.0 +/- 4.1 to 20.7 +/- 4.0 ml.kg.1 (p less than 0.01) (mean decrease 7.3 +/- 4.0 ml.kg.1). EVLW was significantly higher after 4 h on PEEP than after ZEEP (p less than 0.01). Gravimetric values at the end of the experiment were 12.4 +/- 2.8 ml.kg.1 (ZEEP) and 14.7 +/- 4.5 ml.kg.1 (PEEP) (NS). Oxygenation improved in both groups during the resolution of oedema with a more evident and early effect in the PEEP group. It is concluded that mechanical ventilation with PEEP of 1.0 kPa (10 cmH2O) in the resolution phase after experimental hydrostatic oedema improves oxygenation but retards the resolution of oedema.


Hypericum perforatum with Vitex agnus-castus in menopausal symptoms: a randomized, controlled trial.
To evaluate the effectiveness of a phytotherapeutic intervention comprising a combination of Hypericum perforatum (St. John's wort) and Vitex agnus-castus (Chaste tree/berry) in the management of menopausal symptoms. A double-blind, randomized, placebo-controlled, parallel trial was performed over 16 weeks in 100 eligible late-perimenopausal or postmenopausal women experiencing hot flushes and other menopausal symptoms. Herbal combination therapy or placebo tablets were administered twice daily. The primary endpoint was hot flush episodes. Secondary endpoints included Greene Climacteric Scale scores, Hamilton Depression Inventory scores, and Utian Quality of Life Scale scores. Ninety-three women completed the study. Data analysis on an intent-to-treat basis found no significant differences between the two groups for any of the endpoints. Analyses performed at interim data time points revealed no significant differences at week 4, 8, or 12 for daily weighted flushes or scores on the Greene Climacteric Scale or Hamilton Depression Inventory. However, significant improvements across the treatment phase were observed in both the placebo and active treatment groups for these endpoints. No significant change was found for either group on quality of life. The herbal combination of H. perforatum and V. agnus-castus was not found to be superior to placebo for the treatment of menopausal symptoms. The herbal combination was well tolerated with no significant adverse events noted in the short term. Robust findings from quality studies such as this are important for informing the community, healthcare providers, and regulatory authorities.


A shear gradient-activated microfluidic device for automated monitoring of whole blood haemostasis and platelet function.
Accurate assessment of blood haemostasis is essential for the management of patients who use extracorporeal devices, receive anticoagulation therapy or experience coagulopathies. However, current monitoring devices do not measure effects of haemodynamic forces that contribute significantly to platelet function and thrombus formation. Here we describe a microfluidic device that mimics a network of stenosed arteriolar vessels, permitting evaluation of blood clotting within small sample volumes under pathophysiological flow. By applying a clotting time analysis based on a phenomenological mathematical model of thrombus formation, coagulation and platelet function can be accurately measured in vitro in patient blood samples. When the device is integrated into an extracorporeal circuit in pig endotoxemia or heparin therapy models, it produces real-time readouts of alterations in coagulation ex vivo that are more reliable than standard clotting assays. Thus, this disposable device may be useful for personalized diagnostics and for real-time surveillance of antithrombotic therapy in clinic.


TURAN and EVAN mediate pollen tube reception in Arabidopsis Synergids through protein glycosylation.
Pollen tube (PT) reception in flowering plants describes the crosstalk between the male and female gametophytes upon PT arrival at the synergid cells of the ovule. It leads to PT growth arrest, rupture, and sperm cell release, and is thus essential to ensure double fertilization. Here, we describe TURAN (TUN) and EVAN (EVN), two novel members of the PT reception pathway that is mediated by the FERONIA (FER) receptor-like kinase (RLK). Like fer, mutations in these two genes lead to PT overgrowth inside the female gametophyte (FG) without PT rupture. Mapping by next-generation sequencing, cytological analysis of reporter genes, and biochemical assays of glycoproteins in RNAi knockdown mutants revealed both genes to be involved in protein N-glycosylation in the endoplasmic reticulum (ER). TUN encodes a uridine diphosphate (UDP)-glycosyltransferase superfamily protein and EVN a dolichol kinase. In addition to their common role during PT reception in the synergids, both genes have distinct functions in the pollen: whereas EVN is essential for pollen development, TUN is required for PT growth and integrity by affecting the stability of the pollen-specific FER homologs ANXUR1 (ANX1) and ANX2. ANX1- and ANX2-YFP reporters are not expressed in tun pollen grains, but ANX1-YFP is degraded via the ER-associated degradation (ERAD) pathway, likely underlying the anx1/2-like premature PT rupture phenotype of tun mutants. Thus, as in animal sperm-egg interactions, protein glycosylation is essential for the interaction between the female and male gametophytes during PT reception to ensure fertilization and successful reproduction.


The infra-value of human rights in the context of assisted regulation in México.
Infertility represents a problem in the context of reproductive health; to treat it were developed the techniques of assisted human reproduction, despite medical advances, the practice of techniques is subject to medical, legal and ethical dysfunctions. In Mexico, since the late 1980s assisted reproduction clinics were set up in public and private sector hospitals; however, they do not yet have a legal framework to regulate them in a specific way, which causes human rights violations that could be avoided with adequate regulation. This article advances the need to provide Mexico with such regulation as a means of guaranteeing both human rights and the rights of physicians and other health workers involved in these techniques.


Leptospira and rodents in Cambodia: environmental determinants of infection.
We investigated infection of rodents and shrews by Leptospira spp. in two localities of Cambodia (Veal Renh, Kaev Seima) and in four types of habitat (forests, non-flooded lands, lowland rain-fed paddy fields, houses) during the wet and the dry seasons. Habitat preference was common, and rodent and shrew species were found only in houses or in rain-fed paddy fields or in forests. Among 649 small mammals trapped belonging to 12 rodent species and 1 shrew species, 71 of 642 animals tested were carriers of Leptospira according to the 16S ribosomal RNA marker used. Rodent infection was higher in low-slope locations, corresponding to rain-fed paddy fields, especially in the rainy season and in Kaev Seima. Rodents (Rattus exulans) and shrews (Suncus murinus) inhabiting households showed significantly low levels of infections, whereas rodents living in and near to forests (shrubby wasteland, orchards) showed high levels of infection.


Cardiovascular diseases and other evidence for primary care clinical practice.
This issue includes several articles about various cardiovascular illnesses.(1-4) and another on a disease with increased risk for heart disease: hereditary hemochromatosis.(5) Yet another explores some myth busting about mortality and diabetes.(6) Two articles provide data with the support of patient and/or family organizations (Parent Heart Watch(1) and the Iron Disorders Institute(5)). Another 2 articles address maternal-child health, one considers treatment of hyperbilirubinemia,(7) and one describes an innovative team structure for pre-, post-, and intrapartum care.(8) We also provide preliminary data on azithromycin for chronic obstructive pulmonary disease. Pop quiz: What is the common contaminant with cocaine that causes serious side effects? What are these side effects? And another: What nonliver disease should be considered for children with elevated transaminase levels? (See the brief reports for answers.) Two reviews provide up-to-the minute practical facts for vaccinations and treatment-resistant hypertension that can be immediately incorporated into clinical practice. We also have an update on physician perspectives after 2 years of electronic medical record use and another with insights about the satisfaction of family physicians who are working in health centers in the first few years out of their residency.


The pro-inflammatory cytokine IL-22 up-regulates keratin 17 expression in keratinocytes via STAT3 and ERK1/2.
To investigate the regulation of K17 expression by the pro-inflammatory cytokine IL-22 in keratinocytes and its important role in our previously hypothesized "K17/T cell/cytokine autoimmune loop" in psoriasis. K17 expression was examined in the IL-22-treated keratinocytes by real-time quantitative PCR, ELISA, Western blot and Immunofluorescence. In addition, the signaling pathways involved in K17 regulation were investigated with related inhibitors and siRNAs. In addition, K17 expression was examined in the epidermis of IL-22-injected mouse skin. IL-22-induced K17 expression was confirmed in keratinocytes and the epidermis of IL-22-injected mouse skin at both mRNA and protein levels, which is an important complement to the autoimmune loop. We further investigated the regulatory mechanisms and found that both STAT3 and ERK1/2 were involved in the up-regulation of K17 expression induced by IL-22. IL-22 up-regulates K17 expression in keratinocytes in a dose-dependent manner through STAT3- and ERK1/2-dependent mechanisms. These findings indicated that IL-22 was also involved in the K17/T cell/cytokine autoimmune loop and may play an important role in the progression of psoriasis.


High Residual Platelet Reactivity during Aspirin Therapy in Patients with Non-St Segment Elevation Acute Coronary Syndrome: Comparison Between Initial and Late Phases.
High platelet reactivity (HPR) during therapy with acetylsalicylic acid (ASA) is a poor prognostic factor in acute coronary syndromes (ACS). The prevalence of HPR during ACS is greater than that reported in stable diseases. However, it is unclear whether this prevalence of HPR is a transient phenomenon or a characteristic of this high-risk population. The main objective is to compare the effects of ASA on platelet function in the initial and late phases of ACS in a single population. Secondary objectives are: correlation between the tests between themselves and the relationship between the tests and the variation of the inflammatory markers (C-reactive protein and interleukin-6). Seventy patients with non-ST segment elevation (NSTE) ACS in use of 100-200 mg of ASA per day for at least 7 days were prospectively studied. Platelet function was assessed in the first 48 hours and subsequently after 3 months using four methods: VerifyNow™ (VFN), whole blood platelet aggregation (WBPA) with arachidonic acid (AA) and collagen as agonists, and platelet function analyzer (PFA). The level of statistical significance considered was < 0.05. According to the more specific methods (WBPA with AA and VFN), the incidence of HPR was significantly higher in the early phase than in the late phase: WBPA with AA: 31% versus 13%, p = 0.015; VFN: 32% versus 16%, p = 0.049. The other methods tested, which were less specific for ASA, did not show significant differences between phases. The correlation between the methods was weak or moderate (r ranging from 0.3 to 0.5, p < 0.05), and there were no significant associations between HPR and inflammatory markers. The prevalence of HPR during AAS therapy, assessed by specific methods for cyclooxygenase 1 (COX-1), is higher during the acute phase than in the late phase of NSTE ACS.


Nuc-ErbB3 regulates H3K27me3 levels and HMT activity to establish epigenetic repression during peripheral myelination.
Nuc-ErbB3 an alternative transcript from the ErbB3 locus binds to a specific DNA motif and associates with Schwann cell chromatin. Here we generated a nuc-ErbB3 knockin mouse that lacks nuc-ErbB3 expression in the nucleus without affecting the neuregulin-ErbB3 receptor signaling. Nuc-ErbB3 knockin mice exhibit hypermyelination and aberrant myelination at the paranodal region. This phenotype is attributed to de-repression of myelination associated gene transcription following loss of nuc-ErbB3 and histone H3K27me3 promoter occupancy. Nuc-ErbB3 knockin mice exhibit reduced association of H3K27me3 with myelination-associated gene promoters and increased RNA Pol-II rate of transcription of these genes. In addition, nuc-ErbB3 directly regulates levels of H3K27me3 in Schwann cells. Nuc-ErbB3 knockin mice exhibit significant decrease of histone H3K27me3 methyltransferase (HMT) activity and reduced levels of H3K27me3. Collectively, nuc-ErbB3 is a master transcriptional repressor, which regulates HMT activity to establish a repressive chromatin landscape on promoters of genes during peripheral myelination.


Approach to surveying egg masses of the invasive spotted lanternfly (Hemiptera: Fulgoridae).
For the invasive planthopper Lycorma delicatula, eggs are an attractive target for surveys and management because they can persist from September through May before hatching, and remnants may be retained for years after hatching. Efforts to control this invasive species, though, are hampered by imperfect detection, which impedes early detection and rapid response, obscures management impacts, and reduces the fraction of egg masses that can be managed. To estimate egg mass detectability, we conducted 75 duplicate surveys of 20 × 5 m plots located in forest edges and disturbed areas frequently used by L. delicatula. We fit binomial mixture models and investigated the effects of weather, height (above or below 3 m), season (winter or spring), and basal area of trees within plots, finding no evidence that these factors affected detection rate, which averaged 52.2%. We additionally estimated the fraction of L. delicatula eggs that were laid above 3 m, putting them outside of easy reach for management by scraping or targeted ovicide application. This proportion varied with basal area of trees within plots, and the estimated mean was greater than 50% across the range of basal areas in study plots. Finally, we found that counts of old egg masses correlated with counts of new egg masses laid the year prior, but the ability to infer prior years' egg mass counts was limited. Together, these findings inform managers delimiting L. delicatula populations in mixed habitats and those treating egg masses to slow population growth and spread of this pest.


Calcinosis circumscripta: case report and review.
Calcinosis circumscripta, usually associated with scleroderma, Raynaud's phenomenon, and telangiectasia, usually affects middle aged persons and is more common in females than males in a ratio of 6 to 1. The etiology is unknown, and onset of the lesion is slow and insidious. It occurs in the periarticular area as a painful mass with surrounding erythema and edema. It is visible in x-rays as localized, scattered calcification.


Health Smart Homes: User Perspectives.
Health Smart Homes aim to assist the health and well-being of elderly people through digital technologies, by helping them to continue their daily living activities with safety and independence. This paper presents a landscape review to evaluate the effectiveness and feasibility of Health Smart Home technologies for advancing autonomy and quality of life from the perspectives of elderly users. The review was derived from an initial search of peer reviewed journals from three different data sources: PubMed (3808 papers), Google Scholar (7987 papers), and Scopus (595 papers). Of these, fourteen articles eventually met the inclusion criteria for the review and were subjected to further data extraction and quality assessment. The aim of this paper is to identify the perceptions of users by reviewing Health Smart Homes functions, services, benefits and implementation. Health Smart Homes could provide more opportunities to deliver IT-based health services by proactively monitoring and customizing the user environment, to the userâĂŹs needs and preferences.


Influence of microclimate conditions on the cumulative exposure of nursery pigs to swine influenza A viruses.
The objective of this study was to investigate the association between environmental temperature and humidity and the presence of antibodies for two specific strains of swine influenza viruses: A/SW/ON/105-56/12/H3N2 (H3N2_D) and A/SW/ON/84/2012/H1N1 (H1N1_P). A cross-sectional study was performed in a commercial farm, and a total of 450 pigs at 10 weeks of age were blood sampled, by sampling 10 pigs per week for 45 weeks corresponding to 45 batches. Exposure of pigs to H3N2_D and H1N1_P virus was assessed by haemagglutination inhibition assay (HI), and a result of ≥1:40 was considered as indication of a positive exposure status for a specific strain. The selection of those two viruses was based on the fact that H1N1 was the dominant virus in Ontario herds, and H3N2 had been previously isolated in this particular farm. Environmental conditions were recorded through a portable device every 5 min and then summarized using descriptive statistics. The association between HI titres and environmental microconditions, in the nursery, was evaluated through random effect linear and logistic regression. The results showed that the prevalence for H1N1_P was high throughout the study (≥70%); however, for H3N2_D, the seroprevalence declined by the end of the study period. Results also showed an association between cumulative exposure to the viruses and temperature and relative humidity (p < .05). These results suggest that microclimate conditions can influence transmission patterns of influenza viruses in swine barns, and that even a herd with relatively simple demographics could have persistent and cocirculation of two different influenza A viruses IAV strains.


Obesity cardiomyopathy: pathophysiology and evolution of the clinical syndrome.
Obesity produces an increase in total blood volume and cardiac output because of the high metabolic activity of excessive fat. In moderate to severe cases of obesity, this may lead to left ventricular dilation, increased left ventricular wall stress, compensatory (eccentric) left ventricular hypertrophy, and left ventricular diastolic dysfunction. Left ventricular systolic dysfunction may occur if wall stress remains high because of inadequate hypertrophy. Right ventricular structure and function may be similarly affected by the aforementioned morphologic and hemodynamic alterations and by pulmonary hypertension related to the sleep apnea/ obesity hypoventilation syndrome. The term obesity cardiomyopathy is applied when these cardiac structural and hemodynamic changes result in congestive heart failure. Obesity cardiomyopathy typically occurs in persons with severe and long-standing obesity. The predominant causes of death in those with obesity cardiomyopathy are progressive congestive heart failure and sudden cardiac death.


Object-based attention is multisensory: co-activation of an object's representations in ignored sensory modalities.
Within the visual modality, it has been shown that attention to a single visual feature of an object such as speed of motion, results in an automatic transfer of attention to other task-irrelevant features (e.g. colour). An extension of this logic might lead one to predict that such mechanisms also operate across sensory systems. But, connectivity patterns between feature modules across sensory systems are thought to be sparser to those within a given sensory system, where interareal connectivity is extensive. It is not clear that transfer of attention between sensory systems will operate as it does within a sensory system. Using high-density electrical mapping of the event-related potential (ERP) in humans, we tested whether attending to objects in one sensory modality resulted in the preferential processing of that object's features within another task-irrelevant sensory modality. Clear evidence for cross-sensory attention effects was seen, such that for multisensory stimuli responses to ignored task-irrelevant information in the auditory and visual domains were selectively enhanced when they were features of the explicitly attended object presented in the attended sensory modality. We conclude that attending to an object within one sensory modality results in coactivation of that object's representations in ignored sensory modalities. The data further suggest that transfer of attention from visual-to-auditory features operates in a fundamentally different manner than transfer from auditory-to-visual features, and indicate that visual-object representations have a greater influence on their auditory counterparts than vice-versa. These data are discussed in terms of 'priming' vs. 'spreading' accounts of attentional transfer.


Maternal fish oil supplementation in lactation: effect on visual acuity and n-3 fatty acid content of infant erythrocytes.
Studies on formula-fed infants indicate a beneficial effect of dietary DHA on visual acuity. Cross-sectional studies have shown an association between breast-milk DHA levels and visual acuity in breast-fed infants. The objective in this study was to evaluate the biochemical and functional effects of fish oil (FO) supplements in lactating mothers. In this double-blinded randomized trial, Danish mothers with habitual fish intake below the 50th percentile of the Danish National Birth Cohort were randomized to microencapsulated FO [1.3 g/d long-chain n-3 FA (n-3 LCPUFA)] or olive oil (OO). The intervention started within a week after delivery and lasted 4 mon. Mothers with habitual high fish intake and their infants were included as a reference group. Ninety-seven infants completed the trial (44 OO-group, 53 FO-group) and 47 reference infants were followed up. The primary outcome measures were: DHA content of milk samples (0, 2, and 4 mon postnatal) and of infant red blood cell (RBC) membranes (4 mon postnatal), and infant visual acuity (measured by swept visual evoked potential at 2 and 4 mon of age). FO supplementation gave rise to a threefold increase in the DHA content of the 4-mon milk samples (P < 0.001). DHA in infant RBC reflected milk contents (r = 0.564, P < 0.001) and was increased by almost 50% (P < 0.001). Infant visual acuity was not significantly different in the randomized groups but was positively associated at 4 mon with infant RBC-DHA (P = 0.004, multiple regression). We concluded that maternal FO supplementation during lactation did not enhance visual acuity of the infants who completed the intervention. However, the results showed that infants with higher RBC levels of n-3 LCPUFA had a better visual acuity at 4 mon of age, suggesting that n-3 LCPUFA may influence visual maturation.


Variation in the prevalence and abundance of acanthocephalans in brown-nosed coatis Nasua nasua and crab-eating foxes Cerdocyon thous in the Brazilian Pantanal.
Host infection by parasites is influenced by an array of factors, including host and environmental features. We investigated the relationship between host sex, body size and age, as well as seasonality on infection patterns by acanthocephalan in coatis (Procyonidae: Nasua nasua) and in crab-eating foxes (Canidae: Cerdocyon thous ) from the Brazilian Pantanal wetlands. Between 2006 and 2009, we collected faecal samples from these hosts and analyzed for the presence of acanthocephalan eggs. Prevalence, abundance and intensity of eggs of acanthocephalans were calculated. Egg abundance was analyzed using generalized linear models (GLM) with a negative binomial distribution and models were compared by Akaike criteria to verify the effect of biotic and abiotic factors. Prevalence of acanthocephalans was higher in the wet season in both host species but did not differ between host sexes; however, adult crab-eating foxes showed higher prevalence of acanthocephalan eggs than juveniles. In contrast, prevalence of acanthocephalan eggs found in coatis was higher in coati juveniles than in adults. Host age, season and maximum temperature were the top predictors of abundance of acanthocephalan eggs in crab-eating foxes whereas season and host sex were predictors of egg abundance in coatis. The importance of seasonality for abundance of acanthocephalan was clear for both host species. The influence of host-related attributes, however, varied by host species, with host gender and host age being important factors associated with prevalence and parasite loads.


Getting closer: compassion training increases feelings of closeness toward a disliked person.
Evidence-based interventions to favor more harmonious interactions in difficult relationships remain scarce. This study examined whether compassion training may have beneficial effects in an ongoing tense relationship with a disliked person, by reducing schadenfreude toward them and increasing felt interpersonal closeness. 108 participants were assigned to one of three 5-week trainings in a longitudinal randomized controlled study: compassion training, reappraisal training (emotion regulation control condition), or Italian language training (neutral active control condition). The disliked person was not targeted during the trainings to test potential transfer effects. Misfortune scenarios and a measure of interpersonal closeness were used to test whether schadenfreude and closeness feelings toward a disliked person changed from pre- to post-training, across different experimental and control groups. Only compassion and reappraisal trainees reported a decrease of schadenfreude feelings toward the disliked person compared to their pre-training ratings, no changes were observed in the Italian language training. Importantly, feelings of closeness toward the disliked person increased in the compassion training group compared to the other two groups. This increase of closeness feelings could be a central mechanism for improving social interactions. These transfer effects open new perspectives concerning emotion regulation interventions in conflict resolution.


[Rhegmatogenous retinal detachment: a postoperative study of the macula].
To evaluate the structure and function of the macula following rhegmatogenous retinal detachment surgery. Prospective study of patients submitted to scleral buckle surgery or pneumatic retinopexy. The follow-up comprised a complete ophthalmologic exam and optical coherence tomography. The sample was composed of 14 eyes (14 patients), 71.4% operated with the scleral buckle technique, and 28.6% with the pneumatic retinopexy. The age range was from 24 to 59 years (mean of 39.3 years). There was a negative correlation between the final visual acuity and age of patient (r=-0.64, p=0.0127) and between final vision and duration of detachment (r=-0.54, p=0.0447). There was a positive correlation between visual acuity at initial follow-up and that at the final follow-up (r=0.69, p=0.0059). The optical coherence tomography of the initial follow-up showed subclinical foveal detachment in four eyes (28.6% of cases); at the final follow-up the retina was applied by itself with improved vision in all eyes (p=0.031), regardless the time span until reapplication (p=0.5546). The results show that the younger the patient and the earlier the surgical procedure, the better the final visual acuity. Furthermore, there is a positive correlation between initial and final postoperative vision and, all cases that presented foveal detachment on the optical coherence tomography at the initial follow-up had the retina flattened and the vision improved at the final examination.


Preferential localization of the hyperpolarization-activated cyclic nucleotide-gated cation channel subunit HCN1 in basket cell terminals of the rat cerebellum.
Hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels are involved in the control of neuronal excitability and plasticity. In this study, we used immunoblotting and immunohistochemical techniques to reveal the developmental expression and subcellular distribution of the HCN1 subunit in the cerebellar cortex. During postnatal development, the spatio-temporal expression of HCN1 correlated well with the morphological events occurring during the ontogenesis of cerebellar interneurons. Using immunoblotting techniques, HCN1 was weakly detected during the first postnatal week and continued to increase throughout postnatal development, peaking at postnatal day (P)15. At the light-microscopic level, HCN1 immunoreactivity was very weak until P7 whereas from P10-12 to adulthood it was strongly detected in the lower third of the molecular layer and in the Purkinje cell layer. HCN1 was present in axons running through the molecular layer and in the pericellular basket around Purkinje cells at P12, but in the periaxonal plexus (the pinceau) surrounding their initial segment only after P15. Using immunofluorescence, HCN1 colocalized with GAD65 and synaptophysin, demonstrating that the subunit was present in inhibitory axons and axon terminals. At the electron-microscopic level, in adulthood, HCN1 immunoparticles were detected at postsynaptic sites in basket and Purkinje cells but most immunoparticles were found at presynaptic sites in basket cell axons and in terminals. In the axon terminals, the distribution of HCN1 was relatively uniform along the extrasynaptic plasma membrane; this was confirmed using quantitative techniques. The present findings suggest that HCN1 channels may provide a significant route for modulating co-ordinated cerebellar synaptic transmission through basket cells.


Destabilization of nucleosomes by an unusual DNA conformation adopted by poly(dA) small middle dotpoly(dT) tracts in vivo.
Poly(dA) small middle dotpoly(dT) tracts are common and often found upstream of genes in eukaryotes. It has been suggested that poly(dA) small middle dotpoly(dT) promotes transcription in vivo by affecting nucleosome formation. On the other hand, in vitro studies show that poly(dA) small middle dotpoly(dT) can be easily incorporated into nucleosomes. Therefore, the roles of these tracts in nucleosome organization in vivo remain to be established. We have developed an assay system that can evaluate nucleosome formation in yeast cells, and demonstrated that relatively longer tracts such as A(15)TATA(16) and A(34) disrupt an array of positioned nucleosomes, whereas a shorter A(5)TATA(4) tract is incorporated in positioned nucleosomes of yeast minichromosomes. Thus, nucleosomes are destabilized by poly(dA) small middle dotpoly(dT) in vivo in a length-dependent manner. Furthermore, in vivo UV footprinting revealed that the longer tracts adopt an unusual DNA structure in yeast cells that corresponds to the B' conformation described in vitro. Our results support a mechanism in which a unique poly(dA) small middle dot poly(dT) conformation presets chromatin structure to which transcription factors are accessible.


Snf1/AMPK promotes S-phase entrance by controlling CLB5 transcription in budding yeast.
The Saccharomyces cerevisiae Snf1 protein kinase has been reported to be required for adaptation to glucose limitation and for growth on non-fermentable carbon sources. Here we present novel findings indicating that Snf1, the key regulator of cellular energy, is also involved in yeast cell cycle control. The lack of Snf1 α-catalytic subunit down-regulates the growth rate and CLB5 expression, delaying Sld2 phosphorylation and G 1/S transition, in cells grown in 2%, but not in 5% glucose. A non-phosphorylatable Snf1 rescues the slow growth phenotype, whereas a wild type or a phosphomimetic mutant is required to rescue growth rate and the G 1/S delay. Using either Snf1 or Swi6 as a bait, a specific interaction of Snf1 with Swi6, the regulatory subunit of MBF, was detected. In conclusion, this report describes a previously unrecognized role for Snf1 in transcriptional modulation of the G 1 to S transition, differing from the reported AMPK role in controlling the G 1/S transition in multicellular eukaryotes.