Positron emission tomography in clinical neurology.
Positron emission tomography (PET) imaging in clinical neurology serves several purposes: differential diagnosis, especially in the early stage of neurologic disorders, description of pathophysiologic changes that are responsible for manifestation and course of a disease, and evaluation and follow-up of treatment effects. Many of these applications are possible with the most widely available PET tracer, 2-deoxy-2-[18F]fluoro-D-glucose (FDG). Additional tracers are used clinically to detect the disturbance of specific neurotransmitter and receptor systems, blood flow, oxygen metabolism, and amino acid uptake. Main diagnostic issues addressed in this review are early diagnosis of Alzheimer's disease and other dementias, differential diagnosis of movement disorders, diagnosis of recurrent brain tumors, identification of viable tissue in ischemic stroke, and localization of epileptogenic foci. Techniques for presurgical localization of eloquent cortex and monitoring of therapy are presented.


Cutaneous withdrawal reflexes of the upper extremity.
We characterized reflexes of the upper limb elicited by electrical stimulation of the fingers. Surface electromyogram (EMG) was recorded from several upper extremity muscles, and a finger was stimulated through paired ring electrodes. A train of 4-10 shocks at a frequency of 300 Hz and an intensity 4-6 times the perceptual threshold was the most effective stimulus for evoking EMG activity in relaxed arm muscles. Habituation was prominent. Latencies of EMG activity were <100 ms for most proximal and forearm muscles, and at least 40 ms prior to voluntary withdrawal movements. The timing of EMG activity in arm muscles was similar to that of the E2 component of the cutaneomuscular reflex evoked in these same muscles during contraction, and coincided with a silent period in active hand muscles. We conclude that cutaneous stimuli to the fingers activate a complex motor pattern that tends to withdraw the hand at the same time the grasp is released.


The clinical use of Arthur Boothroyd (AB) word lists in Australia: exploring evidence-based practice.
Limited empirical investigation exists validating the use of Arthur Boothroyd (AB) word recognition materials within the Australian clinical context. The current research was undertaken to examine the evidence base and clinical implementation/interpretation of AB words in Australia. An on-line 22-question survey was e-mailed to members of the peak audiology professional body in Australia. Three hundred and twelve responses were recorded between April and June 2015 from audiologists of a range of ages, working in various clinical settings. The survey results suggested audiologists use AB words on a wide range of clients from children <5 to adults ≥80 years, for diverse purposes including diagnosis of retrocochlear pathology, candidacy and validation of rehabilitative options, and client counselling. A majority of respondents reported typically administering one or two word lists per ear, and over 99% of audiologists utilised phonemic scoring. There was no consensus regarding what constitutes a significant difference between any two given scores. Wide variation exists in the administration and interpretation of AB words in Australia. There appears to be a mismatch between clinical utilisation of AB words and existing evidence-based empirical data. Further research is required to improve evidence-based audiologist training, and thereby current clinical use of AB words.


Altered histone abundance as a mode of ovotoxicity during 7,12-dimethylbenz[a]anthracene exposure with additive influence of obesity.
Histones are slowly evolving major chromatin components and chromatin remodeling can incorporate histone variants which differ from canonical histones primary sequences as an epigenetic modification. Several identified histone variants are involved with the environmental stress-induced DNA damage response (DDR). Mechanisms of DDR are better understood in somatic cells than in transcriptionally inactive, prophase-arrested oocytes and epigenetic regulation is under-explored in ovarian toxicology. The objective of this study was to identify ovarian proteomic and histone modifications induced by DMBA exposure and to examine any influence of obesity thereon. Post-pubertal wildtype (KK.Cg-a/a; lean) and agouti (KK.Cg-Ay/J; obese) female mice, were exposed to either corn oil (CT) or DMBA (1 mg/kg) for 7d via intraperitoneal injection (n = 10/treatment). Total ovarian proteome analysis (LC-MS/MS) determined that obesity altered a total of 225 proteins (P < 0.05) and histone 3 was the second least abundant protein (FC = -5.98, P < 0.05). Histone 4 was decreased by 3.33-fold whereas histone variant H3.3 was decreased by 3.05-fold and variants H1.2, H1.4 and H1.1(alpha) were increased by 1.59, 1.90 and 2.01-fold, respectively (P < 0.05). DMBA exposure altered 48 proteins in lean mice but no alterations in histones or histone variants were observed. In obese mice, DMBA exposure altered 120 proteins and histone 2B abundance was increased by 0.30-fold (P < 0.05). In DMBA-exposed mice, obesity altered the abundance of 634 proteins. Histones 4, 3 and 2A type 1-F were decreased by 4.03, 3.71, 0.43-fold, respectively, whereas histone variant H1.2 and linker histone, H15 were increased by 2.72- and 3.07-fold, respectively (P < 0.05). Thus, histones and histone variants respond to DMBA exposure, and this response is more pronounced during obesity, potentially altering ovarian transcriptional regulation.


Congenital Orbital Teratoma with Unilateral Proptosis.
Teratoma is a rare tumor, containing structures originating from all three germinal layers. The most frequent location of teratoma is the gonads. Orbital teratoma is extremely rare. In 1969, Jensen reported that only 40 cases of orbital teratoma existed in the world. We describe a rare case of orbital teratoma in a 15-day girl who presented with marked proptosis of the left eye. The eyeball was embedded within the mass that could be seen all around the globe. Orbitectomy was performed with the impression of retinoblastoma. Histopathological examination was reported as benign mature cystic teratoma; no immature component was identified. The case is being reported because of its rarity and also to highlight the use of modern neuroimaging techniques in making an accurate preoperative diagnosis, which helps in better operative management of these patients.


Ecological Recovery Potential of Freshwater Organisms: Consequences for Environmental Risk Assessment of Chemicals.
Chemical contaminants released into the in the environment may have adverse effects on (non-target) species, populations and communities. The return of a stressed system to its pre-disturbance or other reference state, i.e. the ecological recovery, may depend on various factors related to the affected taxon, the ecosystem of concern and the type of stressor with consequences for the assessment and management of risks associated with chemical contaminants. Whereas the effects caused by short-term exposure might be acceptable to some extent, the conditions under which ecological recovery can serve as a decision criterion in the environmental risk assessment of chemical stressors remains to be evaluated. For a generic consideration of recovery in the risk assessment of chemicals, we reviewed case studies of natural and artificial aquatic systems and evaluate five aspects that might cause variability in population recovery time: (1) taxonomic differences and life-history variability, (2) factors related to ecosystem type and community processes, (3) type of disturbance, (4) comparison of field and semi-field studies, and (5) effect magnitude, i.e., the decline in population size following disturbance. We discuss our findings with regard to both retrospective assessments and prospective risk assessment.


Baylisascaris schroederi Infection in Giant Pandas (Ailuropoda melanoleuca) in Foping National Nature Reserve, China.
The giant panda (Ailuropoda melanoleuca) is the most iconic endangered species in the world, but there is little information about the spatial and temporal distribution of parasites in the wild giant panda population. In total, 193 fecal samples from giant pandas in the Foping National Nature Reserve, People's Republic of China, were analyzed for parasite eggs using a modification of the McMaster technique. The morphology and size of Baylisascaris schroederi eggs were observed under an optical microscope. The prevalence and intensity of B. schroederi infection during the sampling year 2012 were 52.3% (101/193) and 89 eggs/g of feces, respectively, among giant pandas in this population. The prevalence of B. schroederi in the pandas varied during different months of the year, from 7% to 100%, and the prevalences in spring, summer, autumn, and winter were 71, 77, 23, and 18%, respectively. The prevalence was not significantly different between giant pandas that ate two different types of bamboo, but the intensity of infection was higher in the group eating Arundinaria fargesii (P=0.043). Altitude, temperature, and dew point were correlated with the infection intensity (r=-0.224, P<0.001; r=0.328, P<0.001; r=0.328, P=0.028, respectively). There was no correlation between infection intensity and distance to rivers. This study provides a better understanding of B. schroederi prevalence among the wild giant pandas in Foping National Nature, China.


Predicting Factors for Smoking Behavior among Women Who Frequent Nightlife Entertainment Venues around a University in the Northern Region of Thailand.
This cross-sectional survey aims to study the behaviors and predictors for smoking behaviors among women who frequent nightlife entertainment venues around a university in the northern region of Thailand. Samples comprised 279 women who visited nightlife venues around a university in the northern region of Thailand. A questionnaire was used for data collection. Data were analyzed by chi-square and binary logistic regression. The results found that women who frequented nightlife venues and smoked accounted for 32% and 22% of those who smoked inside such venues. Furthermore, the factors identified as predictive of smoking behavior among women who frequented nightlife entertainment venues included frequently visiting nightlife venues more than 3 days per week (odds ratio (OR) = 8.89, 95% confidence interval (CI): 3.31-23.90), having a positive attitude toward smoking (OR = 3.13, 95% CI: 1.56-6.28), having a smoking family member (OR = 2.78, 95% CI: 1.37-5.66), and having a smoking partner (OR = 4.86, 95% CI: 2.38-9.93). Therefore, relevant agencies should continuously promote the right attitudes about smoking to Thai women who frequent nightlife entertainment venues.


Total Knee Arthroplasty Wound Complication Treatment Algorithm: Current Soft Tissue Coverage Options.
Wound complications associated with soft tissue defects following total knee arthroplasty present challenges for the orthopedic surgeon. The scale of early complications include less morbid problems, such as quickly resolving drainage and small superficial eschars, to persistent drainage and full-thickness tissue necrosis, which may require advanced soft tissue coverage. This review outlines current wound management strategies and provides an algorithm to help guide treatment and clinical decision-making. A surgeon's understanding of soft tissue coverage options is essential in protecting the knee prosthesis from a deep infection and to obtain an optimal functional outcome.


Hemodynamic measurements after administration of aprotinin and/or heparin during pancreatic cell autotransplantation in the dog, pig, and monkey.
Transient shock in the form of systemic hypotension and portal venous hypertension has accompanied the portal vein infusion of pancreatic mixed cell autografts in human and canine recipients. The use of aprotinin and/or heparin has been suggested as blocking agents for this vascular reaction. The supernatant from the collagenase-digested pancreatic cells contains the pancreatic shock factor (PSF). A total of 45 animals were studied: 15 mongrel dogs, 15 domestic pigs, and 15 Rhesus monkeys. Femoral artery pressure (FAP), portal venous pressure (PoVP), and cardiac output were recorded continuously. Each animal received 0.05 ml/kg of autologous PSF intravascularly. Each animal species was then divided into three study areas containing five animals with Study 1 receiving PSF plus increasing doses of aprotinin (2,500, 5,000 and 10,000 KIU/kg); Study 2, full heparinization and then PSF; and Study 3, full heparinization and then PSF plus aprotinin. The same vascular hemodynamic factors were measured. Aprotinin blocked the entire shock reaction in the pig (FAP and PoVP), only partially blocked the PoVP elevation in the dog, and blocked neither FAP nor PoVP changes in the monkey. Heparinization did not change the shock reaction in any animal species nor did it change the response to aprotinin blockade in any species. A species response variability exists between the dog, pig, and monkey when aprotinin is injected to block PSF obtained from the animal's own pancreas. If the primate and human responses to aprotinin blockade are similar, aprotinin and/or heparin should not prevent the transient shock associated with human pancreatic mixed cell autotransplantation.


Hepatitis B and concomitant hepatic steatosis.
Hepatic steatosis is becoming more common in Asia with prevalence becoming as common as Western countries. Concomitant Hepatitis B and hepatic steatosis is increasingly encountered in clinical practice. The interaction between the two concomitant conditions at both molecular level and clinical outcome remains to be explored. The present review is aimed at summarizing the existing literature on the complex interaction of the two-concomitant disease.


Effect of gold nanoparticles shape and dose on immunological, hematological, inflammatory, and antioxidants parameters in male rabbit.
Gold nanorods (AuNRs) have gained much attention recent years due to their promising optical and chemical properties and are hence used in applied research and industrial nanotechnology. This study was designed to investigate the effect of gold nanoparticle shape (Gold nanorods vs. gold nanosphere) on immune response in rabbit. Thirty New Zealand white rabbits were divided into six groups (n=5 rabbits). The first group is the control negative received an intravenous (IV) injection of normal saline 0.9%; the second group (vaccinated) is the control positive, and the other four groups were vaccinated and received a single-dose or repeated five consecutive IV doses of 300 mg/kg body weight 50 nm AuNRs or 50 nm gold nanosphere (50 nm AuNSs) dissolved in ultrapure water. Blood and serum were collected for the hematological and biochemical analysis. White blood cells (WBCs) count, lymphocytes, monocytes, eosinophils, and basophils showed significantly (p<0.05) higher values with the repeated-dose AuNRs. g-globulin levels showed a significant difference after 15 days in the single-dose AuNSs. Single-dose AuNSs significantly (p<0.05) increased the immunoglobulin G (IgG) and significantly (p<0.05) decreased the tumor necrosis factor-alpha. In addition, it elicited a significant (p<0.05) decrease in the malondialdehyde levels and a significant (p<0.05) increase of the superoxide dismutase, glutathione peroxidase, and catalase levels. Moreover, evoked red blood cells count, mean corpuscular volume, and mean corpuscular hemoglobin were significantly (p<0.05) lower than the control group. The platelet count, lysozymes, and nitric oxide were significantly (p<0.05) higher in repeated-dose AuNRs. The effect of AuNPs is shape and dose-dependent. The repeated 5 days IV 50 nm AuNRs doses over 15 days showed a significant antioxidant effect, with no considerable toxicity or vascular reactions.


Impact of abiraterone on patient-related outcomes in metastatic castration-resistant prostate cancer: current perspectives.
Abiraterone acetate has established a major role in the treatment paradigm of metastatic castration-resistant prostate cancer ever since pivotal trials, COU-AA-301 and COU-AA-302, have shown benefit in both the second-line and first-line (post- and pre-chemotherapy) setting, respectively, with improvement in overall survival as well as secondary end points such as prostate-specific antigen (PSA) and radiographic response rates, time to PSA progression, and progression-free survival. There has been a lot of interest and emphasis in the evaluation of patient-related outcomes (PROs) as it relates to quality of life, pain, adverse events, fatigue, and among others, in the use of different agents that have been shown to improve survival. This review examines the companion PROs in conjunction with abiraterone acetate use. This is particularly relevant since PROs are increasingly viewed as a key metric for drug label claims in granting approval across regulatory agencies, including the US Food and Drug Administration and the European Medicines Agency.


Microglial/Macrophage Polarization Dynamics following Traumatic Brain Injury.
Activated microglia and macrophages exert dual beneficial and detrimental roles after central nervous system injury, which are thought to be due to their polarization along a continuum from a classical pro-inflammatory M1-like state to an alternative anti-inflammatory M2-like state. The goal of the present study was to analyze the temporal dynamics of microglia/macrophage polarization within the lesion micro-environment following traumatic brain injury (TBI) using a moderate-level controlled cortical impact (CCI) model in mice. We performed a detailed phenotypic analysis of M1- and M2-like polarized microglia/macrophages, as well as nicotinamide adenine dinucleotide phosphate oxidase (NOX2) expression, through 7 days post-injury using real-time polymerase chain reaction (qPCR), flow cytometry and image analyses. We demonstrated that microglia/macrophages express both M1- and M2-like phenotypic markers early after TBI, but the transient up-regulation of the M2-like phenotype was replaced by a predominant M1- or mixed transitional (Mtran) phenotype that expressed high levels of NOX2 at 7 days post-injury. The shift towards the M1-like and Mtran phenotype was associated with increased cortical and hippocampal neurodegeneration. In a follow up study, we administered a selective NOX2 inhibitor, gp91ds-tat, to CCI mice starting at 24 h post-injury to investigate the relationship between NOX2 and M1-like/Mtran phenotypes. Delayed gp91ds-tat treatment altered M1-/M2-like balance in favor of the anti-inflammatory M2-like phenotype, and significantly reduced oxidative damage in neurons at 7 days post-injury. Therefore, our data suggest that despite M1-like and M2-like polarized microglia/macrophages being activated after TBI, the early M2-like response becomes dysfunctional over time, resulting in development of pathological M1-like and Mtran phenotypes driven by increased NOX2 activity.


Natural and man-made health hazards in rural Slovakia.
There is little information on health situation of the people of rural Slovak Republic. The rural environment is often a mixture of natural and man-made hazards, which under some conditions, might turn to be a health risk to humans. The aim of this study was to compare two regions of the Slovak Republic, two different hazards (natural and man-made), two different methods of health outcome measurement (routine statistics and individual diary based data). Ecological study design with focus on cancer incidence analysis was employed in case of natural hazard analysis. Standardized incidence ratios (SIR) were calculated and are presented in paper. Observational study design was employed to study rural gardening practices and their impact on health. Statistically significant differences in SIR were found in rural areas of Spis-Gemer Region (SGR) among males for lip, oral cavity and larynx (1.60, CI 95% 1.12-2.34), respiratory (1.25, CI 95% 1.01-1.55) and digestive organ cancers (1.22, CI 95% 1.01-1.47); hematopoetic cancers are significantly elevated among males in rural areas as well (1.58, CI 95% 1.05-2.39). Pesticide use (83.1% of gardeners use pesticides) without any protective equipment is still widespread among gardeners in rural Slovak Republic (16.9%). The produced fruits and vegetables are substantial part of total fruit and vegetable consumption (51% in summer and 42.7% in winter season) increasing the risk of exposure to pesticides. Our study shows that on ecological level, mortality and morbidity statistics could be used to assess human health status in linkage to broad exposure measures (urban-rural); on dose response level (arsenic in soil) this method lacks sensitivity. Health survey and diary method on the other hand are useful tools in analysis of rural health especially with respect to man-made hazards.


Changes in structural and functional properties of oxygen-evolving complex induced by replacement of D1-glutamate 189 with glutamine in photosystem II: ligation of glutamate 189 carboxylate to the manganese cluster.
A carboxylate group of D1-Glu-189 in photosystem II has been proposed to serve as a direct ligand for the manganese cluster. Here we constructed a mutant that eliminates the carboxylate by replacing D1-Glu-189 with Gln in the cyanobacterium Synechocystis sp. PCC 6803, and we examined the resulting effects on the structural and functional properties of the oxygen-evolving complex (OEC) in photosystem II. The E189Q mutant grew photoautotrophically, and isolated photosystem II core particles evolved oxygen at approximately 70% of the rate of control wild-type particles. The E189Q OEC showed typical S(2) state electron spin resonance signals, and the spin center distance between the S(2) state manganese cluster and the Y(D) (D2-Tyr-160), detected by electron-electron double resonance spectroscopy, was not affected by this mutation. However, the redox potential of the E189Q OEC was considerably lower than that of the control OEC, as revealed by the elevated peak temperature of the S(2) state thermoluminescence bands. The mutation resulted in specific changes to bands ascribed to the putative carboxylate ligands for the manganese cluster and to a few carbonyl bands in mid-frequency (1800 to 1100 cm(-1)) S(2)/S(1) Fourier transform infrared difference spectrum. Notably, the low frequency (650 to 350 cm(-1)) S(2)/S(1) Fourier transform infrared difference spectrum was also uniquely changed by this mutation in the frequencies for the manganese cluster core vibrations. These results suggested that the carboxylate group of D1-Glu-189 ligates the manganese ion, which is influenced by the redox change of the oxidizable manganese ion upon the S(1) to S(2) transition.


Age at menarche and subsequent reproductive events.
A woman's age at menarche may be related to later reproductive performance, including age at first birth and risk of spontaneous abortion. This paper presents data from 2062 women with 4477 pregnancies in the Menstrual and Reproductive Health Study, a prospective study which has been in progress since 1935. Age at menarche is directly related to the age at which a woman marries and conceive a first child, but is unrelated to total fertility, frequency of induced abortion, or risk of stillbirth. Women with either early or late menarche are significantly more likely to have had an ectopic pregnancy. Overall spontaneous abortion risk declines slightly with increasing age at menarche. This trend is not seen, however, when first pregnancies alone are considered. This suggests that the overall trend with age at menarche is not related to a woman's underlying spontaneous abortion risk but rather to unknown selective factors. Women who were very young (less than 11 years) at menarche differ from the others with regard to many measures of reproductive performance. However, these women represent only a small proportion of the total study group.


Drug-induced gingival overgrowth: The nemesis of gingiva unravelled.
Drug-induced gingival overgrowth or enlargement manifests as abnormal growth of the gingiva due to an adverse drug reaction (ADR) in patients treated with anticonvulsants, immunosuppressants, and calcium channel blockers. As gingival enlargement develops, it affects the normal oral hygiene practice and may interfere with masticatory functions. It gradually becomes a source of pain and the condition often leads to disfiguration. Within the group of patients that develop this unwanted effect, there appears to be variability in the extent and severity of the gingival changes. It would seem pertinent to identify and explore possible risk factors and relating them with the treatment plan. This article throws light on respective drugs and their association with gingival overgrowth and approaches to treatment based on current knowledge and investigative observations.


2'5' oligoadenylate synthetase, an interferon induced enzyme: direct assay methods for the products, 2'5' oligoadenylates and 2'5' co-oligonucleotides.
The interferon induced enzyme 2'5' oligoadenylate synthetase produces 2'5' pppA(pA)n the first discovered natural nucleotide with a 2'5' linkage. We describe a direct assay of this enzyme based on separation by thin layer chromatography (TLC) of the substrate ATP and the products 2'5' pppA(pA)n (n larger than or equal to 1). This technique presents obvious advantages compared to the currently used methods. Moreover the enzyme uses other nucleotides as substrates forming co-oligonucleotides 2'5 pppA(pA)n pN (N = U,G,C,dA,dG,dT and dC). Additional procedures are described using different developing solvent systems for the separation of the core-2'5' oligonucleotides (2'5' A(pA)npN) containing AMP-residues entirely and those with another nucleotide at the 2' end.


16S rRNA-Based metagenomic analysis of microbial communities associated with wild Labroides dimidiatus from Karah Island, Terengganu, Malaysia.
This study was designed to evaluate the bacterial composition of the Labroides dimidiatus and its surrounding water. Fish and carriage water samples were obtained from corals of the Karah Island in Terengganu Malaysia. DNA was extracted and the bacteria communities on the skin mucus and stomach as well as water sample were classified (to family level) using the 16S rRNA-based metagenomics analysis. 1,426,740 amplicon sequence reads corresponding to 508 total operational taxonomic units were obtained from the three metagenomics libraries in this study. The Proteobacteria, Bacteroidetes, Firmicutes, Actinobacteria and Fusobacteria were the most dominant bacterial phyla in all samples. A total of 36 different classes and 132 families were identified, many of which had shared presence in all samples while others were exclusive to different sample. Thirty-three of these were identified as pathogenic zoonotic bacterial. The results obtained indicate a strong influence of host environment on the composition of its microbiota. Knowing the composition of the microbiota is the first step toward exploring proper management of this ornamental fish in captivity.


Healthcare costs attributable to congenital cytomegalovirus infection.
Congenital cytomegalovirus infection (cCMV) can cause symptoms at birth as well as long-term impairment. This study estimates cCMV-related healthcare costs in the Netherlands in early childhood. In a nationwide retrospective cohort study, 156 children with cCMV were identified by testing 31 484 neonatal dried blood spots for cCMV. Use of healthcare resources in the first 6 years of life by children with cCMV and a matched cCMV-negative control group were analysed. Mean costs per child were calculated by multiplying healthcare resource use by its reference prices. Children with cCMV were compared with cCMV-negative children. The average total healthcare costs per child were based on the average costs for hospital admissions and consultations by healthcare providers. Mean healthcare costs of children with cCMV (€6113, n=133) were higher than children without cCMV (€3570, n=274), although statistically not significant, with a mean difference of €2544 (95% CI €-451 to €5538). The costs of children with long-term impairment were two times higher in children with cCMV (€17 205) compared with children without cCMV (€8332). Children with cCMV, especially those with long-term impairment and those symptomatic at birth, accrue higher healthcare costs than cCMV-negative children in the first 6 years of life, although this is not statistically significant. This economic impact is of importance in the evaluation of preventive measures against cCMV. NTR3582.


Notch2 blockade enhances hematopoietic stem cell mobilization and homing.
Despite use of newer approaches, some patients being considered for autologous hematopoietic cell transplantation (HCT) may only mobilize limited numbers of hematopoietic progenitor cells (HPCs) into blood, precluding use of the procedure, or being placed at increased risk of complications due to slow hematopoietic reconstitution. Developing more efficacious HPC mobilization regimens and strategies may enhance the mobilization process and improve patient outcome. Although Notch signaling is not essential for homeostasis of adult hematopoietic stem cells (HSCs), Notch-ligand adhesive interaction maintains HSC quiescence and niche retention. Using Notch receptor blocking antibodies, we report that Notch2 blockade, but not Notch1 blockade, sensitizes hematopoietic stem cells and progenitors (HSPCs) to mobilization stimuli and leads to enhanced egress from marrow to the periphery. Notch2 blockade leads to transient myeloid progenitor expansion without affecting HSC homeostasis and self-renewal. We show that transient Notch2 blockade or Notch2-loss in mice lacking Notch2 receptor lead to decreased CXCR4 expression by HSC but increased cell cycling with CXCR4 transcription being directly regulated by the Notch transcriptional protein RBPJ. In addition, we found that Notch2-blocked or Notch2-deficient marrow HSPCs show an increased homing to the marrow, while mobilized Notch2-blocked, but not Notch2-deficient stem cells and progenitors, displayed a competitive repopulating advantage and enhanced hematopoietic reconstitution. These findings suggest that blocking Notch2 combined with the current clinical regimen may further enhance HPC mobilization and improve engraftment during HCT.


Asymmetric primary ringless repair of mitral valve endocarditis: a case report.
The case is presented of a patient with a large mitral valve vegetation. A technique of mitral valve repair involving ringless annuloplasty repair following bileaflet resection of the infected regions of the valve is described. No pledgets or prosthetic material were used in the repair. The patient recovered uneventfully, with trivial mitral regurgitation documented on post-repair echocardiography. This technique may suggest a method for early intervention in mitral endocarditis.


Aneurysm of azygos anterior cerebral artery associated with falcine meningioma: Case Report and review of the literature.
The azygos anterior cerebral artery (ACA) is an uncommon intracranial vascular anomaly of the circle of Willis. Identification of aneurysm from azygos ACA with anterior falcine meningioma is an extremely rare association. The aim of the present study is to report the case of an adult female with a ruptured aneurysm from azygos ACA in association with an anterior falcine meningioma. A 65-year-old female was admitted in the Emergency Department reporting sudden onset of severe headache. Computed tomography (CT) revealed an intracerebral hematoma and an expansive calcified lesion. AngioCT showed the presence of a large aneurysm in the distal portion of the azygos ACA. During the surgical procedure, it was possible to visualize the aneurysm in contact with an expansive lesion arising from the anterior third of the falx. Microsurgical clipping of the aneurysm was performed uneventfully and partial resection of the tumor was done. Histopathological analysis showed a fibrous meningioma. The patient was discharged home on the seventh postoperative day in good clinical conditions. The association of aneurysm from azygos ACA and falcine meningioma is an extremely rare event and must be remembered when expansive masses are present in the vicinity of vascular lesions.


Lipid peroxidation and erythrocyte antioxidant enzymes in patients with Behçet's disease.
In spite of unknown etiology, it is now accepted that reactive oxygen species (ROS) produced by neutrophils may be related to the pathogenesis of Behçet's Disease (BD). The objective was to investigate whether increased production of ROS may affect erythrocyte oxidant/antioxidant system in patients with BD. The levels of malondialdehyde (MDA), one of the end products of lipid peroxidation, in plasma and erythrocyte, and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), antioxidant enzymes, in erythrocyte, also C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured in 22 patients in active stage of the disease and also in 30 healthy controls. Increased CRP, ESR, and MDA levels in plasma and erythrocyte and increased SOD but decreased GSH-Px activities in erythrocytes were observed in the patients, when compared to the controls. In addition, significantly positive correlations between plasma and erythrocyte MDA levels, and erythrocyte MDA-CRP, MDA-ESR, MDA-SOD, SOD-ESR and SOD-CRP levels, but negative correlation between plasma MDA and erythrocyte GSH-Px, were found in BD patients. It may be suggested that increased production of ROS in BD, as reflected by higher plasma and erythrocyte MDA levels, may impair erythrocyte membrane integrity and also may lead to the alterations in the erythrocyte antioxidant defense system, as reflected by higher SOD and lower GSH-Px activities in erythrocytes.


[Foal diseases and foal loss].
An investigation was carried out upon occurrence and course of infectious and non infectious diseases as well as the mortality in foals born and raised at the State Stud Marbach/Lauter between 1982 and 1991. The foals have been investigated from birth to weaning, they consisted of 177 Thoroughbred Arabians and 285 German Warmblood foals (total 462 foals). The diseases were divided into pre-, peri- and postnatal according to their known or assumed cause and onset. There was a preponderance of prenatal diseases (11.25%) whereas the perinatal rate was 1.30% and the postnatal rate of diseases was 8.66%. The rate of infectious diseases increased from the pre- to the postnatal period of life. A comparison between the two breeds showed that 9% of the Arabian foals suffered from infectious diseases whereas only 4.9% of the Warmblood foals were similarly affected. This is probably linked to the lower level of colostral immunoglobulins in the Arab herd, as previously shown by us. The measurement of mare colostral and foal serum IgG as well as the paramunisation of neonatal and weaned foals are important factors in the prevention of infectious diseases.


Cadaver kidney retrieval for transplantation in Canterbury and Westland: 1972-1987.
In Canterbury and Westland, 106 cadaver kidney donors have provided 186 kidneys, which have been transplanted or submitted for transplantation. The overall rate of 16 donor/million population/year, since 1973, is high by international standards [1,2]. Male donors (68%) had a median age of 20 years, and females a median age of 24 years. Motor vehicle accidents were responsible for 58% of deaths, followed by subarachnoid haemorrhage (15%). Cadaver nephrectomy was performed outside normal working hours in 58% of cases. Overall, 10% of kidneys removed were discarded, but none have been discarded since September 1980. Anatomical anomalies were common (42%).


Personal theories of substance use among middle-aged and older adults with bipolar disorder.
Most persons with bipolar disorder (BD) misuse alcohol and/or illicit drugs at some point, yet research specific to older adults with BD is nascent. The current study sought an in-depth understanding of the experiences and meanings of substance use in a sample of adults who self-reported substance misuse. Semi-structured interviews were conducted and thematically analyzed to understand the personal theories of substance use by 12 adults (9 women and 3 men; M = 49 years old) who self-reported diagnoses of BD and regular alcohol or illicit drug use. Findings provide an in-depth picture of the theories middle-aged and older adults with BD have developed to explain their substance use. Participants' theories suggest multiple reasons for substance use, including self-medication; increased confidence with substance use; rejection of prescribed medications; easy access to alcohol; early social exposure/use as facilitator; and living in a culture of substance use. Findings suggest multiple theories for the comorbid link between BD and substance use, primarily that persons with BD use drugs and/or alcohol to relieve stress or manage symptoms. It is clinically relevant to incorporate personal reasons for actively and regularly using substances as part of personalized substance treatment and BD symptom management.


[Analysis of neurological assistance demand in immigrant population].
Immigration has been a growing phenomenon in recent years due to the aging of the population and demographic pressure of immigration in Spain. This study has aimed to know the community out-patient neurological care pressure of the immigrant population and the differences between them and the Spanish population. A descriptive, prospective and observational study of neurological out-patient care in the community of the population covered by the Hospital Universitario La Paz over 12 consecutive months was performed. We analyzed three community out-patient clinics of neurology. The variables analyzed were: demographic (age, gender, nationality, stay time in Spain), care variables (visit type, source of consultation, existence of previous diagnosis and attendance at neurological citation) and diagnostic variables (diagnostic group defined in the ICD-9 M). Of the 4,771 visits analyzed, 8.26% (393) were immigrants. They accounted for a younger population 37.4 +/- 15.2 years, with a larger percentage of women (70.7%; p<0.001). The countries with the greater number of immigrants attended were Ecuador (21.9%) and Colombia (9.9%). Referral to the emergency department was greater for the immigrant patients (p=0.042). Failure to come to the appointment was greater among the immigrant patients (p=0 0.001). Diagnosis of headache and epilepsy were significantly more prevalent in the immigrant population, but syncope, poorly-defined signs and symptoms of those being studied and absence of neurological disorders were more frequent in the Spanish group. Neurological assistance demand of the immigrant population is that expected according to their demographic weight. The most frequent diagnostic groups among the immigrants are headache and epilepsy.


Clinical deterioration during antituberculosis treatment in Africa: incidence, causes and risk factors.
HIV-1 and Mycobacterium tuberculosis cause substantial morbidity and mortality. Despite the availability of antiretroviral and antituberculosis treatment in Africa, clinical deterioration during antituberculosis treatment remains a frequent reason for hospital admission. We therefore determined the incidence, causes and risk factors for clinical deterioration. Prospective cohort study of 292 adults who initiated antituberculosis treatment during a 3-month period. We evaluated those with clinical deterioration over the following 24 weeks of treatment. Seventy-one percent (209/292) of patients were HIV-1 infected (median CD4+: 129 cells/microL [IQR:62-277]). At tuberculosis diagnosis, 23% (34/145) of HIV-1 infected patients qualifying for antiretroviral treatment (ART) were receiving ART; 6 months later, 75% (109/145) had received ART. Within 24 weeks of initiating antituberculosis treatment, 40% (117/292) of patients experienced clinical deterioration due to co-morbid illness (n = 70), tuberculosis related illness (n = 47), non AIDS-defining HIV-1 related infection (n = 25) and AIDS-defining illness (n = 21). Using HIV-1 uninfected patients as the referent group, HIV-1 infected patients had an increasing risk of clinical deterioration as CD4+ counts decreased [CD4+>350 cells/microL: RR = 1.4, 95% CI = 0.7-2.9; CD4+:200-350 cells/microL: RR = 2.0, 95% CI = 1.1-3.6; CD4+<200 cells/microL: RR = 3.0, 95% CI = 1.9-4.7]. During follow-up, 26% (30/117) of patients with clinical deterioration required hospital admission and 15% (17/117) died. Fifteen deaths were in HIV-1 infected patients with a CD4+<200 cells/microL. In multivariate analysis, HIV-1 infection and a low CD4+ count at tuberculosis diagnosis were significant risk factors for clinical deterioration and death. The initiation of ART at a CD4+ count of <350 cells/microL will likely reduce the high burden of clinical deterioration.


Feedback Versus Compliments Versus Both in Suturing and Knot Tying Simulation: A Randomized Controlled Trial.
Suturing is an expected skill for students graduating from health professions programs. Previous studies investigated student experience with teaching sessions utilizing constructive feedback versus compliments but did not investigate the combination of both. In this parallel, randomized controlled trial, participants were divided into three groups: feedback (F), compliments (C), or feedback and compliments (FC). Participants received standardized instruction on simple interrupted suturing and two-handed knot-tying, and were videotaped performing this skill before and after the intervention. Performance was evaluated using a validated Objective Structured Assessment of Technical Skills (OSATS) instrument. Participants completed a preintervention and postintervention survey rating their task enjoyment and self-assessment of performance. Analysis was performed to determine differences between and within the groups using Kruskal-Wallis, Wilcoxon rank-sum, and Mann-Whitney U tests. A total of 31 students participated: 11 in C, 10 in F, and 10 in FC. The groups had similar preintervention OSATS scores. The F and FC groups demonstrated significant improvement in OSATS score after intervention, group C was not significantly different: F median of 11.25-19.75 points (P = 0.002); FC median of 11.75-21 points (P = 0.002); C median of 13-14 points (P = 0.2266). Between the groups FC and F both had significant performance improvement compared with C (P < 0.001 and P = 0.001 respectively). The FC group had a significantly higher rating of their enjoyment of the task on the postintervention survey compared with both the C and F groups with a median rating of 10 compared with 8 and 8 (P = 0.0052 and P = 0.0126, respectively). The combination of feedback and compliments was associated with improvement in performance on suturing and knot-tying similar to the feedback-only group. The FC group rated a higher level of enjoyment of the activity compared to feedback or compliments alone.


Role of corticosterone in trace and delay conditioned fear-potentiated startle in rats.
Emotional events often lead to particularly strong memory formation. Corticosterone, the final product of hypothalamic-pituitary-adrenal (HPA)-axis activation, has been suggested to play a critical role in this effect. Although a great deal of work has implicated the amygdala as a necessary structure for the effects of corticosterone, other studies have suggested a critical role for the hippocampus in determining the involvement of corticosterone. The current experiments examined this question by disrupting corticosterone synthesis with administration of metyrapone (25 or 100 mg/kg) prior to training in either dorsal hippocampus-independent delay fear conditioning or dorsal hippocampus-dependent trace fear conditioning. Metyrapone administration 2 hrs prior to training significantly attenuated corticosterone secretion during training, but these effects were transient as corticosterone levels were similar to control subjects following the test session. As hypothesized, only trace fear conditioning was impaired. This suggests that only fear conditioning tasks that are dependent on the dorsal hippocampus require HPA-axis activation in order to be learned.


Clinical application of a novel endoscopic mask: A randomized controlled trial in aged patients undergoing painless gastroscopy.
Background: Desaturation during painless gastroscopy in aged patients leads to discontinuation of the procedure, prolonged manipulation time and increased risk of severe complications. An endoscopic nasal mask was designed to control hypoxia during the above procedures. A randomized trial was performed to test whether the novel endoscopic mask is helpful for hypoxia during painless gastroscopy in aged patients. Methods: In this randomized, controlled trial, 141 aged patients undergoing painless gastroscopy were randomized into nasal catheter group (69 patients) and endoscopic mask group (65 patients). Primary outcomes were minimum pulse oxygen saturation and incidence of pulse oxygen saturation ≤ 90%. Results: Finally, 134 aged patients were analyzed, including 69 patients in nasal catheter group and 65 patients endoscopic mask group. The minimum pulse oxygen saturation (96.4% ± 4.8%) was higher in the aged endoscopic mask group than in the aged nasal catheter group (94.3% ± 5.6%, P = 0.0075). The incidence of pulse oxygen saturation ≤ 90% did not significantly differ between the endoscopic mask group and nasal catheter group (6.2% VS 15.9%, P = 0.07). There were no severe adverse events in either groups. Conclusion: The endoscopic mask was safely used in aged patients during painless gastroscopy under propofol sedation and significantly improved the minimum pulse oxygen saturation without increasing time to examination or recovery time.


A retrospective, longitudinal study of factors associated with new antipsychotic medication use among recently admitted long-term care residents.
Use of antipsychotic (AP) medications is high and often inappropriate among institutionalized populations. Little is known about the correlates of new AP drug use following admission to long-term care (LTC) settings. This study investigated the frequency and correlates of new AP drug use among newly admitted LTC residents. This longitudinal, retrospective study used data from the interRAI - Nursing Home Minimum Data Set version 2.0 (MDS 2.0) instrument. Data about demographic, clinical and social characteristics, and medication use, were collected in Ontario, Canada, from 2003-2011 by trained nurses. Residents with complete admission and 3-6 month follow-up data were included (N = 47,768). Multivariate logistic regression analyses, stratified by gender, explored correlates of new AP drug use upon admission to LTC. New AP drug users comprised 7 % of the final cohort. Severe cognitive impairment, dementia, and motor agitation were significantly associated with new AP drug use among both sexes. Additionally, behavioural problems, conflicts with staff and reduced social engagement were strong correlates of new AP drug use. Social factors were as strongly associated with new AP drug use after LTC admission as clinical factors. Strategies to prevent the potential misuse of AP drugs upon LTC admission should consider the social determinants of such prescribing.


Effects of curcumin and tannic acid on the aluminum- and lead-induced oxidative neurotoxicity and alterations in NMDA receptors.
Exposure to aluminum (Al) and lead (Pb) can cause brain damage. Also, Pb and Al exposure alters N-methyl-d-aspartate receptor (NMDAR) subunit expression. Polyphenols such as tannic acid and curcumin are very efficient chelator for metals. The effects of curcumin and tannic acid (polyphenols) on Al(3+)- and Pb(2+)-induced oxidative stress were examined by investigating lipid peroxidation (LPO) levels, antioxidant enzyme activities, acetyl cholinesterase (AChE) activity and also NMDA receptor subunits 2A and 2B concentrations in the brain tissue of rats sub-chronically. Rats were divided into seven groups as control, Al, Pb, aluminum-tannic acid treatment (AlT), aluminum-curcumin treatment (AlC), lead-tannic acid treatment (PbT) and lead-curcumin treatment (PbC). After 16 weeks of treatment, LPO levels in the brain and hippocampus were higher in Al(3+)-exposed rats than that of Pb(2+)-exposed group. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in brain tissue of Al- and Pb-exposed rats increased significantly compared with control, while catalase (CAT) and AChE activities decreased. It was observed that metal exposure affected NR2A concentrations more than NR2B concentrations and also that polyphenol treatments increased these receptor protein concentrations.


Superposition-Enhanced Estimation of Optimal Temperature Spacings for Parallel Tempering Simulations.
Effective parallel tempering simulations rely crucially on a properly chosen sequence of temperatures. While it is desirable to achieve a uniform exchange acceptance rate across neighboring replicas, finding a set of temperatures that achieves this end is often a difficult task, in particular for systems undergoing phase transitions. Here we present a method for determination of optimal replica spacings, which is based upon knowledge of local minima in the potential energy landscape. Working within the harmonic superposition approximation, we derive an analytic expression for the parallel tempering acceptance rate as a function of the replica temperatures. For a particular system and a given database of minima, we show how this expression can be used to determine optimal temperatures that achieve a desired uniform acceptance rate. We test our strategy for two atomic clusters that exhibit broken ergodicity, demonstrating that our method achieves uniform acceptance as well as significant efficiency gains.


LTP-like plasticity in the visual system and in the motor system appear related in young and healthy subjects.
LTP-like plasticity measured by visual evoked potentials (VEP) can be induced in the intact human brain by presenting checkerboard reversals. Also associated with LTP-like plasticity, around two third of participants respond to transcranial magnetic stimulation (TMS) with a paired-associate stimulation (PAS) protocol with a potentiation of their motor evoked potentials. LTP-like processes are also required for verbal and motor learning tasks. We compared effect sizes, responder rates and intercorrelations as well as the potential influence of attention between these four assessments in a group of 37 young and healthy volunteers. We observed a potentiation effect of the N75 and P100 VEP component which positively correlated with plasticity induced by PAS. Subjects with a better subjective alertness were more likely to show PAS and VEP potentiation. No correlation was found between the other assessments. Effect sizes and responder rates of VEP potentiation were higher compared to PAS. Our results indicate a high variability of LTP-like effects and no evidence for a system-specific nature. As a consequence, studies wishing to assess individual levels of LTP-like plasticity should employ a combination of multiple assessments.


The influence of turmeric and curcumin on cholesterol concentration of eggs and tissues.
An experiment was conducted in order to study the hypocholesteremic effect of tumeric and its coloring principle namely curcumin both in the presence and absence of dietary cholesterol. Laying hens were used as the experimental animals and they were fed the experimental diets for a duration of 8 weeks. The results of the experiment showed that tumeric or various levels of curcumin had no adverse effect on egg production, egg weight and feed to egg ratio. Moreover tumeric or various levels of curcumin both in the presence and absence of dietary cholesterol did not reduce the fat or cholesterol levels of plasma, liver or the egg yolk. An interesting finding from this experiment was that the egg yolk cholesterol levels of cholesterol fed groups sharply increased at the beginning of the experiment, and thereafter they gradually decreased and tended to approach the normal levels at the termination of the experiment. The possible reasons for variation in egg yolk cholesterol levels of cholesterol-fed groups with time is discussed.


Catalytic Acceptorless Dehydrogenation (CAD) of Secondary Benzylic Alcohols into Value-Added Ketones Using Pd(II)-NHC Complexes.
For the creation of adaptable carbonyl compounds in organic synthesis, the oxidation of alcohols is a crucial step. As a sustainable alternative to the harmful traditional oxidation processes, transition-metal catalysts have recently attracted a lot of interest in acceptorless dehydrogenation reactions of alcohols. Here, using well-defined, air-stable palladium(II)-NHC catalysts (A-F), we demonstrate an effective method for the catalytic acceptorless dehydrogenation (CAD) reaction of secondary benzylic alcohols to produce the corresponding ketones and molecular hydrogen (H2). Catalytic acceptorless dehydrogenation (CAD) has been successfully used to convert a variety of alcohols, including electron-rich/electron-poor aromatic secondary alcohols, heteroaromatic secondary alcohols, and aliphatic cyclic alcohols, into their corresponding value-added ketones while only releasing molecular hydrogen as a byproduct.


InterMineR: an R package for InterMine databases.
InterMineR is a package designed to provide a flexible interface between the R programming environment and biological databases built using the InterMine platform. The package offers access to the flexible query builder and the library of term enrichment tools of the InterMine framework, as well as interoperability with other Bioconductor packages. This facilitates automation of data retrieval tasks as well as downstream analysis with existing statistical tools in the R environment. InterMineR is free and open source, released under the LGPL licence and available from the Bioconductor project and Github (https://bioconductor.org/packages/release/bioc/html/InterMineR.html, https://github.com/intermine/interMineR). Supplementary data are available at Bioinformatics online.


In Vitro Modulation of Complement Activation by Therapeutically Prospective Analogues of the Marine Polychaeta Arenicin Peptides.
The widespread resistance to antibiotics in pathogenic bacteria makes the development of a new generation of antimicrobials an urgent task. The development of new antibiotics must be accompanied by a comprehensive study of all of their biological activities in order to avoid adverse side-effects from their application. Some promising antibiotic prototypes derived from the structures of arenicins, antimicrobial peptides from the lugworm Arenicola marina, have been developed. Previously, we described the ability of natural arenicins -1 and -2 to modulate the human complement system activation in vitro. In this regard, it seems important to evaluate the effect of therapeutically promising arenicin analogues on complement activation. Here, we describe the complement-modulating activity of three such analogues, Ar-1[V8R], ALP1, and AA139. We found that the mode of action of Ar-1[V8R] and ALP1 on the complement was similar to that of natural arenicins, which can both activate and inhibit the complement, depending on the concentration. However, Ar-1[V8R] behaved predominantly as an inhibitor, showing only a moderate increase in C3a production in the alternative pathway model and no enhancement at all of the classical pathway of complement activation. In contrast, the action of ALP1 was characterized by a marked increase in the complement activation through the classical pathway in the concentration range of 2.5-20 μg/mL. At the same time, at higher concentrations (80-160 μg/mL), this peptide exhibited a complement inhibitory effect characteristic of the other arenicins. Peptide AA139, like other arenicins, exhibited an inhibitory effect on complement at a concentration of 160 μg/mL, but was much less pronounced. Overall, our results suggest that the effect on the complement system should be taken into account in the development of antibiotics based on arenicins.


Knowledge translation concerns for the CONSORT-PRO extension reporting guidance: a review of reviews.
This review of reviews aimed to appraise the use of the CONSORT-PRO Extension as an evaluation tool for assessing the reporting of patient-reported outcome (PROs) in publications, and to describe the reporting of PRO research across reviews. We also outlined how variation in such evaluations impacts knowledge translation and may lead to potential misuse of the CONSORT-PRO Extension. We systematically searched Medline, Pubmed and CINAHL from 2013 to 2025 March 2021 for reviews of the completeness of reporting of PRO endpoints according to CONSORT-PRO criteria. Two reviewers extracted details of each review, the percentage of included studies that addressed each CONSORT-PRO item, and key recommendations from each review. Fourteen reviews met inclusion criteria, and only six of these used the full CONSORT-PRO checklist with minimal justified modifications. The remaining eight studies made significant or unjustified adjustments to the CONSORT-PRO Extension. Review studies also varied in how they scored multi-component CONSORT-PRO items. CONSORT-PRO items were often unreported in trial reports, and certain CONSORT-PRO items were reported less often than others. The reporting of statistical approaches to dealing with missing PRO data were poor in RCTs included in all 14 review articles. Studies reviewing PRO publications often omitted recommended CONSORT-PRO items from their evaluations, which may cause confusion among readers regarding how best to report their PRO research according to the CONSORT-PRO extension. Many trials published since CONSORT-PRO's release did not report recommended CONSORT-PRO items, which may lead to misinterpretation and consequently to research waste.


Development and evaluation of an educational resource for parents of children with 22q11.2 deletion syndrome about the psychiatric manifestations of the condition.
Parents of children with 22q11.2 deletion syndrome (22q11DS) report concern about the psychiatric manifestations of the condition, but typically receive little information about this in clinical encounters and instead find information about it elsewhere. We developed an educational booklet about the psychiatric manifestations of 22q11DS and assessed its utility among parents of children with the condition. First, six parents of individuals with 22q11DS completed cognitive interviews to review an established generic booklet about the genetics of psychiatric conditions-and to suggest 22q11DS-specific adaptations. We used these suggestions to develop a novel booklet specific to psychiatric conditions and 22q1DS. Then, before and 1-month after reading the novel 22q11DS-specific online booklet, 73 parents of children with 22q11DS (with/without psychiatric conditions) completed validated scales (measuring empowerment, stigma, intolerance of uncertainty), an adapted version of a scale measuring worry about their child developing psychiatric illness, and purpose-designed items assessing perceptions of understanding of 22q11DS and mental illness, confidence in recognizing early signs, etc. After reading the 22q11DS online booklet, participants' feelings of empowerment increased (p = 0.002), while feelings of worry about their child developing psychiatric illness decreased (p = 0.05), and they reported better understanding 22q11DS and mental illness, and increased confidence in recognizing early warning signs. There is potential benefit in broadly distributing this educational booklet to parents of children with 22q11DS.


Evaluation of self-perception of mechanical ventilation knowledge among Brazilian final-year medical students, residents and emergency physicians.
To present self-assessments of knowledge about mechanical ventilation made by final-year medical students, residents, and physicians taking qualifying courses at the Brazilian Society of Internal Medicine who work in urgent and emergency settings. A 34-item questionnaire comprising different areas of knowledge and training in mechanical ventilation was given to 806 medical students, residents, and participants in qualifying courses at 11 medical schools in Brazil. The questionnaire's self-assessment items for knowledge were transformed into scores. The average score among all participants was 21% (0-100%). Of the total, 85% respondents felt they did not receive sufficient information about mechanical ventilation during medical training. Additionally, 77% of the group reported that they would not know when to start noninvasive ventilation in a patient, and 81%, 81%, and 89% would not know how to start volume control, pressure control and pressure support ventilation modes, respectively. Furthermore, 86.4% and 94% of the participants believed they would not identify the basic principles of mechanical ventilation in patients with obstructive pulmonary disease and acute respiratory distress syndrome, respectively, and would feel insecure beginning ventilation. Finally, 77% said they would fear for the safety of a patient requiring invasive mechanical ventilation under their care. Self-assessment of knowledge and self-perception of safety for managing mechanical ventilation were deficient among residents, students and emergency physicians from a sample in Brazil.


A stereocontrolled synthesis of delta-trans-tocotrienoloic acid.
[reaction: see text] A concise stereoselective total synthesis of a naturally occurring polymerase beta inhibitor, delta-trans-tocotrienoloic acid (2), is described. The key step in the synthesis is an acid-catalyzed cyclodehydration reaction. Additionally, this report corrects a previously reported structural assignment, defines the absolute stereochemistry of 2, and defines key structural requirements for polymerase beta inhibition.


The effect of full-spectrum fluorescent lighting on reproductive traits of caged turkey hens.
Large White turkey breeder hens were exposed to either incandescent or full-spectrum (FS) fluorescent lighting during two 20-week reproductive cycles in closed confinement. Data were recorded for body weights, feed intake, and reproductive traits. Body weights and feed intake were similar between treatments in both egg laying cycles. In addition, there were no significant differences in egg production, fertility, hatchability, or poult weight between the incandescent and FS fluorescent light treatment in either the first or second year egg laying cycle. It was concluded that exposure of breeder turkey hens to FS fluorescent light in closed confinement results in reproductive performance similar to that obtained with incandescent lighting.


Follicle-stimulating hormone encapsulation in the cholesterol-modified chitosan nanoparticles via molecular dynamics simulations and binding free energy calculations.
Follicle-stimulating hormone (FSH) is widely applied in the modern ovarian stimulation techniques. However, it must be administered daily because of its short half-life. Recently, the cholesterol (CS) modified chitosan (CTS) nanogels have attracted significant interest as promising controlled release protein delivery because of their ability to minimize the aggregation and irreversible denaturation of proteins. Herein, we report a molecular dynamics (MD) simulation investigation on the molecular mechanisms of FSH encapsulation in the CS-CTS nanogels. The MD simulations have been performed using the GROMACS software for up to 200ns simulation time. Furthermore, the binding free energy has been calculated by the molecular mechanics [MM] with Poisson-Boltzmann [PB] and surface area solvation (MM/PBSA) method by using the g_mmpbsa tool. Our findings suggest that the main driving force of the formation of the CS-CTS nanogels is the hydrophobic interactions between the CS-CS moieties in water. The results have also indicated that the CS-CTS nanogel formation can occur through the hydrogen bonding in addition to the hydrophobic interactions. The obtained data demonstrate that the FSH encapsulation into the CS-CTS nanogels is a gradual process driven by the hydrophobic interactions between the hydrophobic patch of FSH and the hydrophobic nanodomains of the nanogel. Our results also reveal that except in the hydrophobic patch region, the flexibility of FSH was reduced in the presence of the nanogel. This study provides the elucidation of the nanogel-FSH interactions at the molecular level and presents new perspective for the ideal design and applications of the CS-CTS nanogel in protein delivery.


Highly accurate quantification of hydroxyproline-containing peptides in blood using a protease digest of stable isotope-labeled collagen.
Collagen-derived hydroxyproline (Hyp)-containing dipeptides and tripeptides, which are known to possess physiological functions, appear in blood at high concentrations after oral ingestion of gelatin hydrolysate. However, highly accurate and sensitive quantification of the Hyp-containing peptides in blood has been challenging because of the analytical interference from numerous other blood components. We recently developed a stable isotope-labeled collagen named "SI-collagen" that can be used as an internal standard in various types of collagen analyses employing liquid chromatography-mass spectrometry (LC-MS). Here we prepared stable isotope-labeled Hyp-containing peptides from SI-collagen using trypsin/chymotrypsin and plasma proteases by mimicking the protein degradation pathways in the body. With the protease digest of SI-collagen used as an internal standard mixture, we achieved highly accurate simultaneous quantification of Hyp and 13 Hyp-containing peptides in human blood by LC-MS. The area under the plasma concentration-time curve of Hyp-containing peptides ranged from 0.663 ± 0.022 nmol/mL·h for Pro-Hyp-Gly to 163 ± 1 nmol/mL·h for Pro-Hyp after oral ingestion of 25 g of fish gelatin hydrolysate, and the coefficient of variation of three separate measurements was <7% for each peptide except for Glu-Hyp-Gly, which was near the detection limit. Our method is useful for absorption/metabolism studies of the Hyp-containing peptides and development of functionally characterized gelatin hydrolysate.


Influence of iron alone or with fluoride on caries development in desalivated and intact rats.
Sugar is used as a vehicle for iron fortification in communities where anemia is prevalent. The purpose of the present study was to investigate the relationship between caries experience and iron concentration in sugar fed to rats subjected to a severe cariogenic challenge. Desalivated and intact animals were assigned to 4 different diet subgroups, 3 receiving iron sucrose (350, 175 and 88 ppm Fe) and a control group. The influence of iron sugar combined with 10 ppm F in drinking water was explored in an additional study. Iron reduces the incidence of smooth-surface carries in desalivated rats at concentrations as low as 88 ppm Fe. In addition, a combination of iron and fluoride reduced the incidence of dental caries in our rats.


Low-Yield Genesis of Coalbed Methane Stripper Wells in China and Key Technologies for Increasing Gas Production.
For the problem where numerous coalbed methane (CBM) stripper wells exist in China, this paper analyzes the genesis of the stripper wells from the aspects of geological conditions and development technologies combined with the CBM development of some typical blocks. A series of key secondary stimulation technologies for CBM stripper wells are put forward, including low-damage fracturing fluid for preventing reservoir damages, proppants with multigraded sizes for supporting multilevel fractures, large-scale fracture network stimulation (FNS) for improving reservoir permeability, and coal measure gas development for increasing the exploitable resources within a single well scope, as well as coordinated stimulation of parent-child wells for the overall production improvement of low-yield blocks. Also, it is pointed out that all types of stripper wells could adopt the low-damage fracturing fluid and multigraded proppant and optimize the drainage schedule to inhibit reservoir damage and promote the maintenance of fracture conductivity. For resource-controlled stripper wells, large-scale FNS of coal seams, coal measure gas development, and coordinated stimulation of parent-child wells could be adopted according to the differences in resource abundance and coal seam distribution. For the stripper wells controlled by the coal structure and ground stress, FNS of the surrounding rock could be conducted to construct stable and efficient channels for CBM migration. In addition, by conducting large-scale FNS, the stimulation effect of fracturing-controlled stripper wells improves, while after unblocking and reopening the existing reservoir fractures of the drainage-controlled stripper wells, an optimized drainage schedule could be adopted to prevent reservoir damages and promote the maintenance of fracture conductivity.


Age-related deficits in the cerebellar beta adrenergic signal transduction cascade in Fischer 344 rats.
Localization of age-related deficits in the cerebellar beta adrenergic signal transduction cascade were investigated electrophysiologically using forskolin (FORSK) and adenosine-3',5'-cyclic monophosphothioate Sp-isomer (Sp-cAMPS) applied via pressure ejection from extracellular multibarreled glass electrodes to activate the transduction cascade. In young rats, 100 microM FORSK activated AC, and 100 microM Sp-cAMPS activated protein kinase A; thus, both increased GABAergic inhibition of Purkinje cell firing. In aged rats, however, 100 microM FORSK was unable to increase GABAergic inhibition of Purkinje cell firing. In addition, 1 mM 7 beta-decacetyl-7 beta-(gamma-N-methylpiperazino)butyryl-forskolin, an analog of FORSK, was also unable to increase GABAergic inhibition in aged rats. In contrast, Sp-cAMPS was able to increase GABAergic inhibition in aged rats, but higher doses were required than in young rats, Isoproterenol (ISO), a beta adrenergic agonist, was ineffective in increasing GABAergic inhibition of Purkinje firing in aged rats when tested alone, but ISO was effective in increasing Purkinje cell inhibition when ISO was tested with Sp-cAMPS. The results of this experiment indicate that one age-related deficit in the cerebellar beta adrenergic system occurs at the level of protein kinase A activation.


Body Mass Index and Risk of Gallbladder Cancer: Systematic Review and Meta-Analysis of Observational Studies.
To provide a quantitative assessment of the association between excess body weight, interpreted as increased body mass index (BMI), and the risk of gallbladder cancer (GBC). We identified eligible studies in Medline and EMBASE up to 1 February 2015, and reference lists of retrieved articles. Summary relative risks with their 95% confidence intervals were calculated in a random-effects model. Subgroup analyses were performed according to study design, gender, geographic location, ascertainment of exposure and adjustment for confounders. A total of 12 cohort studies and 8 case-control studies were included in the meta-analysis. Overall, compared with "normal" weight, the summary relative risks of GBC were 1.14 (95% CI, 1.04-1.25) for overweight individuals (BMI 25-30 kg/m²) and 1.56 (95% CI, 1.41-1.73) for obese individuals (BMI > 30 kg/m²). Obese women had a higher risk of GBC than men did (women: SRRs 1.67, 95% CI 1.38-2.02; men: SRRs 1.42, 95% CI 1.21-1.66), and there was significant association between overweight and GBC risk in women (SRRs 1.26, 95% CI 1.13-1.40), but not in men (SRRs 1.06, 95% CI 0.94-1.20). Findings from this meta-analysis indicate that obesity is associated with an increased risk of GBC, especially in women. Overweight is associated with GBC risk only in women.


The OSHA standard setting process: role of the occupational health nurse.
1. Occupational health nurses are the health professionals most often involved with the worker who suffers as a result of ineffective or non-existent safety and health standards. 2. Occupational health nurses are familiar with health and safety standards, but may not understand or participate in the rulemaking process used to develop them. 3. Knowing the eight basic steps of rulemaking and actively participating in the process empowers occupational health nurses to influence national policy decisions affecting the safety and health of millions of workers. 4. By actively participating in rulemaking activities, occupational health nurses also improve the quality of occupational health nursing practice and enhance the image of the nursing profession.


Contact order, transition state placement and the refolding rates of single domain proteins.
Theoretical studies have suggested relationships between the size, stability and topology of a protein fold and the rate and mechanisms by which it is achieved. The recent characterization of the refolding of a number of simple, single domain proteins has provided a means of testing these assertions. Our investigations have revealed statistically significant correlations between the average sequence separation between contacting residues in the native state and the rate and transition state placement of folding for a non-homologous set of simple, single domain proteins. These indicate that proteins featuring primarily sequence-local contacts tend to fold more rapidly and exhibit less compact folding transition states than those characterized by more non-local interactions. No significant relationship is apparent between protein length and folding rates, but a weak correlation is observed between length and the fraction of solvent-exposed surface area buried in the transition state. Anticipated strong relationships between equilibrium folding free energy and folding kinetics, or between chemical denaturant and temperature dependence-derived measures of transition state placement, are not apparent. The observed correlations are consistent with a model of protein folding in which the size and stability of the polypeptide segments organized in the transition state are largely independent of protein length, but are related to the topological complexity of the native state. The correlation between topological complexity and folding rates may reflect chain entropy contributions to the folding barrier.


Adenosine receptors and renal ischaemia reperfusion injury.
One of the frequent clinical complications that results in billions of dollars in healthcare costs annually in the United States is acute kidney injury (AKI). Ischaemia reperfusion (IR) injury is a major cause AKI. Unfortunately, no effective treatment or preventive measure for AKI exists. With increased surgical complexity coupled with increasing number of elderly, the incidence of AKI is becoming more frequent. Adenosine is a metabolic breakdown product of adenosine triphosphate (ATP) and contributes to the regulation of multiple physiological events. Extracellular adenosine activates four subtypes of adenosine receptors (AR) including A1 AR, A2 A AR, A2 B AR and A3 AR. In the kidney, adenosine regulates glomerular filtration rate, vascular tone, renin release and is an integrative part of tubular glomerular feedback signal to the afferent arterioles. In addition, each AR subtype powerfully modulates renal IR injury. The A1 AR activation protects against ischaemic insult by reducing apoptosis, necrosis and inflammation. Activation of A2 A AR protects against renal injury by modulating leucocyte-mediated inflammation as well as directly reducing renal tubular inflammation. Activation of A2 B AR acts via direct activation of renal parenchymal as well as renovascular receptors and is important in kidney preconditioning. Finally, activation of A3 AR exacerbates renal damage following renal IR injury while A3 AR antagonism attenuates renal damage following ischaemic insult. Latest body of research suggests that kidney AR modulation may be a promising approach to treat ischaemic AKI. This brief review focuses on the signalling pathways of adenosine in the kidney followed by the role for various AR modulations in protecting against ischaemic AKI.


Noninnocently Behaving Bridging Anions of the Widely Distributed Antioxidant Ellagic Acid in Diruthenium Complexes.
Dinuclear compounds [L2Ru(μ-E)RuL2](n) where L is acetylacetonate (acac(-), 2,4-pentanedionate), 2,2'-bipyridine (bpy), or 2-phenylazopyridine (pap) and EH4 is ellagic acid, an antioxidative bis-catechol natural product, were studied by voltammetric and spectroelectrochemical techniques (UV-vis-NIR and electron paramagnetic resonance (EPR)). The electronic structures of the isolated forms (NBu4)2[(acac)2Ru(μ-E)Ru(acac)2] ((NBu4)2[1]), [(bpy)2Ru(μ-E)Ru(bpy)2]ClO4 ([2]ClO4), and [(pap)2Ru(μ-E)Ru(pap)2] ([3]) were characterized by density functional theory (DFT) in conjunction with EPR and UV-vis-NIR measurements. The crystal structure of (NBu4)2[1] revealed the meso form and a largely planar Ru(μ-E)Ru center. Several additional charge states of the compounds were electrochemically accessible and were identified mostly as complexes with noninnocently behaving pap(0/•-) or bridging ellagate (E(n-)) anions (n = 2, 3, 4) but not as mixed-valence intermediates. The free anions E(n-), n = 1-4, were calculated by time-dependent DFT to reveal NIR transitions for the radical forms with n = 1 and 3 and a triplet ground state for the bis(o-semiquinone) dianion E(2-).


Affinities of Teilhardina (Primates, Omomyidae) with description of a new species from North America.
Teilhardina is a fifth primate found in Early Tertiary rocks of both Europe and North America. Both T. belgica and the new North American species are anaptomorphines; however, neither species is ideally suited for the ancestry of the New World Omomyidae. Pelycodus and the Adapidae are not closely related to Teilhardina and Torrejonian Palenochtha is probably not in the ancestry of omomyids. A combination of dental characters in earliest Anemorhysis suggest this primate is the most generalised known omomyid.


Tracheostomy in special groups of critically ill patients: Who, when, and where?
Tracheostomy is one of the most common procedures undertaken in critically ill patients. It offers many theoretical advantages over translaryngeal intubation. Recent evidence in a heterogeneous group of critically ill patients, however, has not demonstrated a benefit for tracheostomy, in terms of mortality, length of stay in Intensive Care Unit (ICU), or incidence of ventilator-associated pneumonia. It may be a beneficial intervention in articular subsets of ICU patients. In this article, we will focus on the evidence for the timing of tracheostomy and its effect on various subgroups of patients in critical care.


[Estimate of the dose of chlorinated pesticides consumed daily by the Italian population (1978-1984)].
This work reports an estimate of the doses of chlorinated pesticides taken with a total diet by the Italian population in the period 1978-84. Previous researches, carried out in 1971-72, had regarded both uncooked and cooked diets, ready for the consumption. It was found that the amount of the considered pesticides taken in total (HCB, gamma-BHC and total-BHC, Aldrin/Dieldrin, Heptachlor/Heptachlor-epoxide and DDT total-equivalent) calculated as a sum of the percentage of each acceptable daily intake (A.D.I.), at that time recommended was near the limit of acceptability (98.5% for cooked diets and 107.0% for uncooked diets). In addition it was found that nearly the 40% of the dose assumed in all came from milk and its derivates (butter, cheese). Then considering the contribution of milk and derivates to the amount of pollutants assumed with a total diet, a new evaluation has been done, with regard to the period 1978-84, i.e. after the prohibition of the use of these pesticides in Italy and in other industrialized countries. Then the data have been processed, with regard to 211 samples of foods (90 of milk, 45 of cheese, 76 butter) coming from determinations carried out by the Multizonal Laboratory of Hygiene and Prevention of Ferrara, Milano, Udine, Bolzano, Trento, Pescara and from the Institute of Hygiene of Rome University "La Sapienza" in the period mentioned. Furthermore, alimentary consumptions of milk, butter and cheese in 1978-84 have been evaluated, and amounts of chlorinated pesticides taken with these foods have been calculated. Finally the dose taken with these foods has been extrapolated to a total diet. It has come out that the doses (estimated) taken with the total diet have notably decreased between 1971-72 and 1978-84. An anomaly is yet represented by HCB: while the quantity taken with food has decreased from 1971-72 to 1978-84 (from 3.7 to 1.3 micrograms/man/day), the concentrations in human adipose tissues have increased (from 1.02 to 1.99 mg/Kg). It can reasonably mean that assumption of HCB is not prevalently alimentary, but that it is due to other factors of environmental contamination. The data of the doses of chlorinated pesticides taken have also been compared with the respective ADI indicated in 1971-72 and in 1978-84.


Evaluated fate and effects of atrazine and lambda-cyhalothrin in vegetated and unvegetated microcosms.
Contaminants such as nutrients, metals, and pesticides can interact with constructed wetlands and existing drainage ditches used as agricultural best-management practices. Our research has shown that the presence of macrophytes and a hydrologic regime aid in the transfer and transformation of pesticides associated with agricultural runoff. This study consisted of application of both atrazine (triazine herbicide) and lambda-cyhalothrin (pyrethroid insecticide) to vegetated and unvegetated microcosms in order to measure the fate and effects of pesticides applied at suggested field application rates. Exposures focused on monocultures of Ludwigia peploides (water primrose) and Juncus effusus (soft rush). Pesticide sorption was evident through concentrations of atrazine and lambda-cyhalothrin in plant tissue as high as 2461.4 and 86.50 microg/kg, respectively. Toxicity was measured in water from unvegetated microcosms for 28 days and in Chironomus tentans (midge larvae) exposed to sediment collected from 3 h to 56 days in microcosms receiving the pesticide combination. The comparative survival of test organisms in this study suggests that effective mitigation of pesticides from runoff can depend on the macrophyte contact and vegetative attributes associated with ditches.


Lymphedema secondary to breast cancer: how choice of measure influences diagnosis, prevalence, and identifiable risk factors.
Research on secondary lymphedema primarily uses indirect methods for diagnosis. This paper compares prevalence and cumulative burden following breast cancer surgery, as well as personal, treatment, and behavioral characteristics associated with lymphedema, using different assessment techniques. Lymphedema status was assessed at three-monthly intervals between six- and 18-months post-surgery in a population-based sample of Australian women with recently diagnosed, unilateral, invasive breast cancer, using three methods: bioimpedance spectroscopy (BIS), difference between sum of arm circumferences (SOAC) and self-report. Depending on the method, point prevalence ranged between 8 to 28%, with 1 in 5 to 2 in 5 women experiencing lymphedema at some point in time. Of those with lymphedema defined by BIS, almost 40%-60% went undetected, and 40%-12% were misclassified as having lymphedema, based on self-report and SOAC, respectively. The choice of measure also had significant implications for identified risk factors. Over 10 characteristics were associated with lymphedema, however only one, experiencing other upper-body symptoms at baseline, influenced odds of lymphedema across all three methods. These findings highlight that secondary lymphedema poses a significant public health problem. Utilizing the most accurate and reliable method for assessment is crucial to advance our understanding of preventive and treatment strategies.


The Impact of Mental Fatigue on a Strength Endurance Task: Is there a Role for the Movement-Related Cortical Potential?
Several mechanisms have been proposed to explain how mental fatigue degrades sport performance. In terms of endurance performance, a role for an increased perceived exertion has been demonstrated. Utilizing electroencephalography (EEG) and, more specifically, the movement-related cortical potential (MRCP), the present study explored the neural mechanisms that could underly the mental fatigue-associated increase in perceived exertion. Fourteen participants (age: 23 ± 2 y, 5 females, 9 males) performed one familiarisation and two experimental trials in a randomised, blinded, cross-over study design. Participants had to complete a submaximal leg extension task after a mentally fatiguing task (EXP; individualized 60-min Stroop task) or control task (CON; documentary). The leg extension task consisted of performing 100 extensions at 35% of 1RM, during which multiple physiological (heart rate, EEG, ratings of perceived exertion) and psychological measures (self-reported feeling of mental fatigue, cognitive load, motivation) were assessed. Self-reported feeling of mental fatigue was higher in EXP (72 ± 18) compared to CON (37 ± 17; p < 0.001). A decrease in flanker accuracy was detected only in EXP (from 0.96 ± 0.03 to 0.94 ± 0.03; p < 0.05). No significant differences between conditions were found in MRCP characteristics and perceived exertion. Specifically in EXP, alpha wave power increased during the leg extension task (p < 0.01). Mental fatigue did not impact the perceived exertion or MRCP characteristics during the leg extension task. This could be related to low perceived exertion and/or the absence of a performance outcome during the leg extension task. The increase in alpha power during the leg extension task in EXP, suggests participants may engage a focused internal attention mechanism to maintain performance and mitigate feelings of fatigue.


Mutual detection of Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus in blood and saliva of Cameroonians with and without Kaposi's sarcoma.
Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) are prevalent in sub-Saharan Africa, together with HIV; the consequent burden of disease is grave. The cofactors driving transmission of the two viruses and pathogenesis of associated malignancies are not well understood. We measured KSHV and EBV DNA in whole blood and saliva as well as serum antibodies levels in 175 Cameroonians with Kaposi's sarcoma and 1,002 age- and sex-matched controls with and without HIV. KSHV seroprevalence was very high (81%) in controls, while EBV seroprevalence was 100% overall. KSHV DNA was detectable in the blood of 36-46% of cases and 6-12% of controls; EBV DNA was detected in most participants (72-89%). In saliva, more cases (50-58%) than controls (25-28%) shed KSHV, regardless of HIV infection. EBV shedding was common (75-100%); more HIV+ than HIV- controls shed EBV. Cases had higher KSHV and EBV VL in blood and saliva then controls, only among HIV+ participants. KSHV and EBV VL were also higher in HIV+ than in HIV- controls. Cases (but not controls) were more likely to have detectable KSHV in blood if they also had EBV, whereas shedding of each virus in saliva was independent. While EBV VL in saliva and blood were modestly correlated, no correlation existed for KSHV. Numerous factors, several related to parasitic coinfections, were associated with detection of either virus or with VL. These findings may help better understand the interplay between the two gammaherpesviruses and generally among copathogens contributing to cancer burden in sub-Saharan Africa.


A comprehensive study of the anatomical variations of the circle of willis in adult human brains.
Cerebrovascular diseases such as stroke, aneurysms and arterio-venous malformations are very much prevalent in our country. Circle of Willis, as an anastomotic polygon at the base of the brain forms an important collateral network to maintain adequate cerebral perfusion. Changes in the normal morphology of the circle may condition the appearance and severity of symptoms of cerebrovascular disorders, such as aneurysms, infarctions and other vascular anomalies. A possible link between abnormalities of the circle of Willis and the mentally ill patients has been observed. The aim of the present study is to have an intimate knowledge of the variations in the cerebral arterial circle and to clarify the clinical importance of these variations in certain forms of cerebrovascular diseases. So an attempt was made to analyse the anatomical variations of the circle in a random population. The work was based on fifty adult brains from persons died of diverse causes. The materials were obtained during routine autopsy studies. The base of the brain including the brain stem with intact arterial circle was preserved in 10% formalin for 10 days. The circle of Willis and its major branches were carefully dissected under water using a magnifying lens. The variations were recorded and photographed. Majority of the circles (52%) showed anomalies. Hypoplasia was the most frequent anomaly and was found in 24% of the brains. Accessory vessels in the form of duplications/triplications of anterior communicating artery were seen in 12% of the circles. The embryonic origin of the posterior cerebral artery from the internal carotid persisted in 10% of the circles. An incomplete circle due to the absence of one or other posterior communicating artery was found in 6% of the specimens.Variations are more frequent in posterior half of the circle. The anatomical variations of the circle of Willis were probably genetically determined, develop in early embryonic stage and persist in post natal life. The amplitude of neck movements, racial, environmental and hemodynamic factors may also modify these variations. These anomalies may alter the occurrence, severity of symptoms, treatment options and recovery from certain cerebrovascular disorders viz., stroke and aneurysms. A detailed knowledge of the vascular variants is useful to surgeons in planning their shunt operations, choice of the patients and also keeps away inadvertent vascular traumas during surgeries.


Dysfunction in early auditory processing in major depressive disorder revealed by combined MEG and EEG.
Patients with major depressive disorder (MDD) show impairments in cognitive functions. However, neural mechanisms underlying these disturbances are poorly understood. We investigated whether MDD affects neural mechanisms of involuntary attention studied by auditory evoked potentials (AEPs) and auditory evoked magnetic fields (AEFs). AEPs and AEFs were studied in a passive odd-ball paradigm in 13 drug-free patients with unipolar MDD during an acute episode and 12 age-and sex-matched healthy subjects. Auditory responses to monaurally presented frequent "standard" tones, infrequent "deviant" tones (10% and 20% frequency change) and occasional "novel" sounds (complex sounds) were simultaneously recorded with whole-head magnetoencephalography (MEG) and electroencephalography (EEG). P1 and P1m latencies were decreased in patients with MDD, compared with those in healthy subjects. Further, the mismatch negativity amplitude to the 10% frequency deviance in the EEG, but not in the MEG, was increased in MDD. We observed no differences in N1/N1m and P3a responses in the MEG and EEG. The magnitude of decrease in P1/P1m latency correlated negatively with the severity of depression in the patients. Early auditory processing is impaired in patients with MDD during an acute episode, probably reflecting dysfunctional frontotemporal neural circuits. These dysfunctions may contribute to the cognitive disturbances observed in people with MDD.


Cognition in a patient with very mild right-sided hemiparkinsonism.
Non-demented patients with Parkinson's disease (PD), especially if they are high functioning and early in the course of their disease, usually exhibit mild deficits in anterograde recall memory for verbal and non-verbal material, visuospatial reasoning, visuomotor construction, temporal ordering and sequencing. Impairments in problem solving and verbal fluency tests may also occur. PD patients with predominantly right-sided symptoms usually exhibit more severe difficulties with verbal than with non-verbal tasks. We report a case of a highly educated right-handed man with very mild right-sided hemiparkinsonism who never received anti-Parkinsonian or other psychoactive medication. Our patient showed anterograde and retrograde amnesia for faces and spatial locations and difficulties on complex visuospatial tasks that required manual responses, but normal to above average performance on all other cognitive tests. The specific pattern of cognitive loss early in PD may depend on which spatial, facial or verbal pre-frontal striatal circuits are deprived of their dopaminergic inputs.


Entorhinal Cortex: Antemortem Cortical Thickness and Postmortem Neurofibrillary Tangles and Amyloid Pathology.
The entorhinal cortex, a critical gateway between the neocortex and hippocampus, is one of the earliest regions affected by Alzheimer disease-associated neurofibrillary tangle pathology. Although our prior work has automatically delineated an MR imaging-based measure of the entorhinal cortex, whether antemortem entorhinal cortex thickness is associated with postmortem tangle burden within the entorhinal cortex is still unknown. Our objective was to evaluate the relationship between antemortem MRI measures of entorhinal cortex thickness and postmortem neuropathological measures. We evaluated 50 participants from the Rush Memory and Aging Project with antemortem structural T1-weighted MR imaging and postmortem neuropathologic assessments. Here, we focused on thickness within the entorhinal cortex as anatomically defined by our previously developed MR imaging parcellation system (Desikan-Killiany Atlas in FreeSurfer). Using linear regression, we evaluated the association between entorhinal cortex thickness and tangles and amyloid-β load within the entorhinal cortex and medial temporal and neocortical regions. We found a significant relationship between antemortem entorhinal cortex thickness and entorhinal cortex (P = .006) and medial temporal lobe tangles (P = .002); we found no relationship between entorhinal cortex thickness and entorhinal cortex (P = .09) and medial temporal lobe amyloid-β (P = .09). We also found a significant association between entorhinal cortex thickness and cortical tangles (P = .003) and amyloid-β (P = .01). We found no relationship between parahippocampal gyrus thickness and entorhinal cortex (P = .31) and medial temporal lobe tangles (P = .051). Our findings indicate that entorhinal cortex-associated in vivo cortical thinning may represent a marker of postmortem medial temporal and neocortical Alzheimer disease pathology.


Mosaic pbpX genes of major clones of penicillin-resistant Streptococcus pneumoniae have evolved from pbpX genes of a penicillin-sensitive Streptococcus oralis.
Penicillin-resistant clinical isolates of Streptococcus pneumoniae contain mosaic penicillin-binding protein (PBP) genes that encode PBPs with decreased affinity for beta-lactam antibiotics. The mosaic blocks are believed to be the result of gene transfer of homologous PBP genes from related penicillin-resistant species. We have now identified a gene homologous to the pneumococcal PBP2x gene (pbpX) in a penicillin-sensitive Streptococcus oralis isolate M3 from South Africa that diverged by almost 20% from pbpX of penicillin-sensitive pneumococci, and a central sequence block of a mosaic pbpX gene of Streptococcus mitis strain NCTC 10712. In contrast, it differed by only 2-4% of the 1 to 1.5 kb mosaic block in pbpX genes of three genetically unrelated penicillin-resistant S. pneumoniae isolates, two of them representing clones of serotype 6B and 23F, which are prevalent in Spain and are also already found in other countries. With low concentrations of cefotaxime, transformants of the sensitive S. pneumoniae R6 strain could be selected containing pbpX genes from either S. mitis NCTC 10712 or S. oralis M3, demonstrating that genetic exchange can already occur between beta-lactam-sensitive species. These data are in agreement with the assumption that PBPs as penicillin-resistance determinants have evolved by the accumulation of point mutations in genes of sensitive commensal species.


Platelet Activation Is Limited during Transcatheter Aortic Valve Implantation in Patients on Aspirin Monotherapy and without per Procedural Clinical Complications.
Transcatheter aortic valve implantation (TAVI) is an established treatment option for symptomatic patients with severe aortic valve stenosis (AS). During and early after the procedure, both ischemic events (predominantly stroke) and bleedings remain prevalent. The optimal antithrombotic regimen is still debated. Single- versus dual-antiplatelet therapy is associated with a lower rate of severe bleeding, without difference in thrombotic complications. Although platelets have been empirically targeted, little is known on their contribution to these events primarily related to embolization of thrombotic material and tissue-derived debris from the wounded aortic valve and large vessels. The objective of this study was to assess local platelet activation in blood sampled in the ascending aorta immediately before and within minutes postimplantation. A series of 18 patients with AS on monotherapy with aspirin successfully underwent TAVI with the self-expandable Medtronic CoreValve by transfemoral route. No clinical thrombotic complication occurred at 30-day follow-up. Compared with patients with stable coronary artery disease unscathed of AS and similarly treated by low-dose aspirin, AS patients displayed a chronic state of platelet activation before TAVI, assessed in venous blood using various biomarkers. However, per procedure, in aortic blood, no change occurred between the two time points in the plasma levels of serotonin or 12-lipoxgenase products, or membrane exposure of granule markers CD62-P and CD63. Our results suggest that local acute platelet activation is limited during TAVI on monotherapy with aspirin.