Neurocognitive functioning in HIV-1 infection: effects of cerebrovascular risk factors and age.
This study examined the interactive effects of cerebrovascular risks, advancing age, and HIV infection on neurocognition, and explored whether pharmacological treatment of cerebrovascular risk factors attenuated neurocognitive dysfunction. Participants included 98 HIV-seropositive adults (cerebrovascular risk: 23.5%; age > 50: 27.6%). Cerebrovascular risk was associated with slower processing speed even after controlling for age effects (b = -2.071; p =.04), and the interaction of age and cerebrovascular risk was associated with poorer verbal fluency (b = 1.276, p =.002). Participants with pharmacologically untreated cerebrovascular risk demonstrated reduced processing speed, learning/memory, and executive functioning relative to those on medication. Poor cerebrovascular health confers significant risk for HIV+ individuals, and this effect may be of greater consequence than advancing age. The cognitive impact of risk appears to be more pronounced in the absence of adequate pharmacological treatment.


[Gastric cancer in pregnancy -- a case report].
Nausea and vomiting are common sufferings of pregnant woman. No gynaecologist would consider carcinoma of the stomach as a probable differential diagnosis according the extremely rare probability of this disease during pregnancy. Consequently, a late diagnosis in pregnancy can result in spreading throughout the whole abdomen. In this advanced stage, it is only possible to recommend palliative care to the patient followed by short survival. Fetal metastasis is a rare entity, therefore caesarean section and chemotherapy should not be performed until fetal maturity. If vomiting and nausea are prolonged after the sixteenth week of pregnancy a malignant disease of the stomach should be excluded. Only in case of short delay between symptoms and diagnosis, the stomach cancer can be resected totally followed by a better overall survival of the patient.


Discontinuing antidepressants and benzodiazepines upon becoming pregnant. Beware of the risks of abrupt discontinuation.
Two of my patients are planning to become pregnant. One is taking paroxetine and the other lorazepam. We have discussed what to do when they become pregnant and have decided they should stop taking these drugs as soon as pregnancy is confirmed. Is this the right decision? The decision to discontinue these drugs during pregnancy should be based on scientific evidence rather than "hearsay" that women should not take psychotropic medications during pregnancy. Recent epidemiologic studies have documented the relative safety of these drugs, so women should not feel compelled to stop taking them when they become pregnant. If, after receiving appropriate evidence-based information, a woman decides to stop taking the drugs, they should be gradually tapered off to avoid abrupt discontinuation syndrome.


Effect of haemorrhage on renin concentration in superficial and deep venous outflows of the cat kidney.
1. Plasma renin concentration is significantly higher in the subcapsular venous outflow, which drains the superficial cortex, than in the deep venous outflow, which drains the inner half of the cortex and medulla of the cat kidney. The purpose of these experiments was to observe whether this pattern is preserved or disrupted by a stimulus to renin release. 2. Plasma renin concentration in arterial samples and in the superficial and deep renal venous outflows was measured before and after haemorrhage which produced a 24 +/- 6.7% drop in mean blood pressure in 13 cats. 3. After haemorrhage, total kidney plasma flow and glomerular filtration rate (GFR) did not change significantly. There was a rise in arterial plasma renin concentration. Venous minus arterial plasma renin concentration increased significantly in the deep venous outflow, but not in the superficial outflow. 4. The results suggest that both superficial and deep cortical venous drainage of the cat kidney should be considered when measuring renal renin release. In addition, they suggest that there may be differences in the response of superficial and deep juxtaglomerular apparatuses to haemorrhage.


Robust and conventional neuropsychological norms: diagnosis and prediction of age-related cognitive decline.
The aim of the study was to compare the performance of Robust and Conventional neuropsychological norms in predicting clinical decline among healthy adults and in mild cognitive impairment (MCI). The authors developed Robust baseline cross sectional and longitudinal change norms from 113 healthy participants retaining a normal diagnosis for at least 4 years. Baseline Conventional norms were separately created for 256 similar healthy participants without follow-up. Conventional and Robust norms were tested in an independent cohort of longitudinally studied healthy (n=223), MCI (n=136), and Alzheimer's disease (AD, n=162) participants; 84 healthy participants declined to MCI or AD (NL-->DEC), and 44 MCI declined to AD (MCI-->AD). Compared to Conventional norms, baseline Robust norms correctly identified a higher proportion of NL-->DEC with impairment in delayed memory and attention-language domains. Both norms predicted decline from MCI-->AD. Change norms for delayed memory and attention-language significantly incremented baseline classification accuracies. These findings indicate that Robust norms improve identification of healthy individuals who will decline and may be useful for selecting at-risk participants for research studies and early interventions.


Dividing the pie: A quantitative review on plant density responses.
Plant population density is an important variable in agronomy and forestry and offers an experimental way to better understand plant-plant competition. We made a meta-analysis of responses of even-aged mono-specific stands to population density by quantifying for 3 stand and 33 individual plant variables in 334 experiments how much both plant biomass and phenotypic traits change with a doubling in density. Increasing density increases standing crop per area, but decreases the mean size of its individuals, mostly through reduced tillering and branching. Among the phenotypic traits, stem diameter is negatively affected, but plant height remains remarkably similar, partly due to an increased stem length-to-mass ratio and partly by increased allocation to stems. The reduction in biomass is caused by a lower photosynthetic rate, mainly due to shading of part of the foliage. Total seed mass per plant is also strongly reduced, marginally by lower mass per seed, but mainly because of lower seed numbers. Plants generally have fewer shoot-born roots, but their overall rooting depth seems hardly affected. The phenotypic plasticity responses to high densities correlate strongly with those to low light, and less with those to low nutrients, suggesting that at high density, shading affects plants more than nutrient depletion.


Vision related quality of life in patients with keratoconus.
Purpose. The purpose of this study is to evaluate the vision related quality of life in patients with keratoconus by using the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25). Methods. Thirty patients presented with keratoconus (keratoconus group) and 30 healthy patients (control group) were included in this study. Twenty patients were using rigid gas permeable and 10 patients were not using contact lenses in keratoconus group. High and low contrast visual acuity and mean K values of the patients were recorded. Each subject completed the 25-item NEI-VFQ-25. Results. All subscales of NEI-VFQ-25 were lower in the keratoconus patients. The difference was more evident in the subscales of general vision, ocular pain, near vision, vision-specific mental health, vision-specific role difficulties, and peripheral vision (P < 0.05). Overall composite score was 75.2 ± 17.2 in the keratoconus group and 93.2 ± 5.6 in the control group (P = 0.00). Contact lens wearers had higher best corrected visual acuity in comparison with noncontact lens wearers (P = 0.028). Patients with low visual acuity (logMAR > 0.4) in the better eye had lower distance vision, social functioning, mental health, and role difficulties. Meanwhile, patients with low visual acuity (logMAR > 0.4) in the worse eye had lower general health scores (P < 0.05). Conclusions. Vision related quality of life was worse in keratoconus patients. Success in the contact lens usage and maintaining higher visual acuity may improve vision related quality of life.


Prevalence of obesity in preschool Greek children, in relation to parental characteristics and region of residence.
The aim of this retrospective cohort study was to record the prevalence of overweight and obesity in relation to parental education level, parental body mass index and region of residence, in preschool children in Greece. A total of 2374 children (1218 males and 1156 females) aged 1-5 years, stratified by parental educational level (Census 1999), were examined from 105 nurseries in five counties, from April 2003 to July 2004, Weight (kg) and height (cm) were obtained and BMI (kg/m2) was calculated. Both the US Centers for Disease Control (CDC) and the International Obesity Task Force (IOTF) methods were used to classify each child as "normal", "at risk of overweight" and "overweight". Parental demographic characteristics, such as age and educational level and parental anthropometrical data, such as stature and body weight, were also recorded with the use of a specifically designed questionnaire. The overall estimates of at risk of overweight and overweight using the CDC method was 31.9%, 10.6 percentage points higher than the IOTF estimate of 21.3% and this difference was significant (p < 0.001). Children with one obese parent had 91% greater odds for being overweight compared to those with no obese parent, while the likelihood for being overweight was 2.38 times greater for children with two obese parents in the multivariate model. Both methods used to assess prevalence of obesity have demonstrated that a high percentage of the preschool children in our sample were overweight. Parental body mass index was also shown to be an obesity risk factor in very young children.


[Biochemical characteristics of skeletal tumors].
Tissues of 38 varieties of human skeletal tumors were studied by a complex of biochemical assays. It was found that such biochemical parameter as concentration of connective tissue components points to the degree of malignancy. The peculiarities of biochemical characteristics of skeletal tumors are of importance in differential diagnosis and may be used in the examination of tissue specimens obtained by biopsy or during surgery.


Body sodium in rats: response to DOCA, adrenalectomy, changes in salt intake, and a salt load.
Body Na was studied by an isotope method in rats on Na-free diet plus a choice of H2O and 0.5% or 0.1% NaCl. Two groups (1 on 0.5%, 1 on 0.1% NaCl) had Silastic deoxycorticosterone acetate (DOCA) implants, two similar groups were sham operated, and a fifth group (on 0.5% NaCl) underwent adrenalectomy (ADX). Saline consumption increased in DOCA-treated and ADX rats. Body Na was increased by DOCA and by drinking 0.5% NaCl compared with 0.1% NaCl. Body Na after intraperitoneal NaCl loading (which raised body Na 8-10%) and withdrawal of NaCl drinking fluids was analyzed by use of the model y = Ae-a(t-d) + Be-bt, where y is body Na at time t and d is delay before fast rate constant a is established; d was greater on the lower Na intake. Rate constant a was not reduced by chronic DOCA treatment. Coefficient B of the slow exponential, representing the basal level to which body Na falls on zero Na intake, and equivalent to Hollenberg's "set-point," was higher in DOCA-treated rats. This analysis makes use of Hollenberg's set-point concept, but the findings suggest that the set-point is related to mineralocorticoid activity and is thus presumably variable.


Actinobacillus minor sp. nov., Actinobacillus porcinus sp. nov., and Actinobacillus indolicus sp. nov., three new V factor-dependent species from the respiratory tract of pigs.
The results of DNA-DNA relatedness experiments and comparisons of sequences of genes coding for 16S rRNA were used to determine the genetic relationships of selected V factor-dependent species belonging to the family Pasteurellaceae and obtained from the porcine respiratory tract. These results showed that the Minor group and taxa C, D plus E, and F are distinct phylogenetic groups that are separate from each other and from other members of the family Pasteurellaceae. On the basis of these results, three new species, corresponding to the Minor group, taxa D plus E, and taxon F, are proposed; the names of these new species are Actinobacillus minor (type strain, NM305), Actinobacillus porcinus (type strain, NM319), and Actinobacillus indolicus (type strain, 46KC2), respectively.


Acute posttraumatic subdural hematomas: "intradural" computed tomographic appearance as a favorable prognostic factor.
Posttraumatic acute subdural hematoma carries a high postoperative mortality rate. Preservation of subarachnoid spaces in preoperative computed tomographic (CT) scans may be interpreted as a favorable prognostic factor. Thirty-one cases of posttraumatic acute subdural hematoma operated on consecutively, with an interval from trauma to surgery of less than 4 hours and a Glasgow Coma Scale score of less than 8, were reviewed. The immediate and long-term results were evaluated with reference to preoperative CT images, distinguishing cases with preserved subarachnoid spaces from the others. In 5 of the 31 cases, preoperative CT scans showed intact subarachnoid spaces and the absence of blood in the cerebrospinal fluid. These cases presented a much better postoperative course than did the others. The presence of intact subarachnoid spaces in CT scans for patients with acute subdural hematomas may be interpreted as an extremely favorable prognostic factor; this may be attributed to the protective effect of the integral visceral membrane of the hematoma, which prevents the diffusion of neurotoxic and vasoactive substances into the subarachnoid spaces. This group of hematomas was classified as "intradural," with reference to the concept of the "subdural compartment" described in studies conducted using an electron microscope.


Pentoxifylline does not delay bacterially induced preterm delivery in rabbits.
Our purpose was to determine whether pentoxifylline, a potent cytokine inhibitor, would delay bacterially induced preterm delivery in rabbits. The study was a randomized, blinded, prospective trial. Twenty-seven rabbits underwent laparotomy. Of these, five (shams) received an intrauterine injection of endotoxin-free water, and the remaining 22 received an injection of 10(5) Escherichia coli into the lower uterine segment. Postoperatively the animals that received the Escherichia coli were divided into two groups. The placebo group (n = 11) received subcutaneous injections of saline solution three times a day and the treatment group (n = 11) received pentoxifylline 20 mg/kg/day in three divided doses. The following parameters were evaluated: (1) time until delivery, (2) time until death, and (3) intrauterine pathologic features. All five of the sham rabbits were delivered at term without any evidence of infection. There were no differences in the preterm delivery rates between the placebo group (eight of 11) and the pentoxifylline-treated group (seven to 11). However, there was a trend toward prolonging time until death in the treatment group. There were no differences in intrauterine pathologic feature between the placebo and treatment groups. Pentoxifylline does not delay Escherichia coli induced preterm delivery in rabbits.


Extended boiling of peanut progressively reduces IgE allergenicity while retaining T cell reactivity.
Current peanut oral immunotherapy is hampered by frequent adverse events. It has been shown that boiling can reduce peanut allergenicity. Hypoallergenic peanut products have the potential to reduce treatment-related reactions during desensitization. To show that extended boiling (for up to 12 h) can progressively reduce peanut allergenicity while retaining T cell reactivity. Raw peanuts were boiled for half, 1, 2, 4 and 12 h in deionized water. After dehydration, boiled and raw peanuts were ground, defatted and soluble proteins extracted in PBS and cooking water (leachate) retained. SDS-PAGE, Western blot, inhibition ELISA, mass spectrometry and skin prick test were used to characterize changes to peanut allergens and human IgE reactivity. T cell responses to raw and boiled peanut extracts were determined by proliferation of CD4+/CD25+/CD134+ T cells in peanut-allergic and non-allergic individuals. Extended boiling progressively reduced peanut allergenicity through a combination of leaching of allergens into cooking water, fragmentation of allergens and denaturation of conformational epitopes. Two-hour boiling led to an eightfold reduction in IgE binding capacity of boiled peanuts as determined by inhibition ELISA, while 12-h boiling led to a 19-fold reduction. Mass spectrometry revealed an increasing number of unique allergen peptides with longer boiling times. Raw, 2- and 12-h boiled peanut extracts were equivalent in their ability to stimulate T cell activation and proliferation. Progressive reduction in peanut allergenicity with extended boiling does not affect T cell reactivity. Boiled peanuts may be a candidate for oral immunotherapy.


[The kidneys and old age].
With more detailed knowledge on renal function at advanced age it became clear that age-related changes of renal function are less severe than previously thought. However, these changes are significantly aggravated by classical cardiovascular risk factors such as hypertension, diabetes and smoking. As a consequence, in elderly with such co-morbidity the appearance of a primary kidney disease or acute renal failure may cause a serious deterioration of renal function. In addition, impaired homeostasis with respect to salt (and fluid) balance has important consequences for the management of the elderly who is exposed to the twin risks of dehydration and fluid overload. Finally, the kidney is the main route of excretion for many drugs and their active metabolites. Diminution of renal function with age underlies, at least in part, the known predisposition of the elderly to side effects of their medication such as non-steroidal anti-inflammatory drugs.


[Nosocomial infections due to rotavirus and respiratory syncytial virus in pediatric wards: a 2-year study].
Rotavirus and respiratory syncytial virus (RSV) infections represent up to 30% of the totality of nosocomial infections in paediatric wards. We studied the importance of these infections in the paediatric wards of the University Hospital Center of Poitiers, France, from October 1996 to September 1998. We defined as nosocomial an infection acquired after 3 days of hospitalization for rotavirus and after 7 days for RSV. The 274 cases of children presenting rotavirus gastroenteritis or RSV infection within this period were studied. Rotavirus was detected in stools by using an agglutination test and RSV was diagnosed in nasopharyngeal aspirations by direct examination with an immunofluorescence assay (IFA), cell culture and serotyping with IFA. We noted 50 rotavirus and 224 RSV infections, with a first epidemic of RSV subgroup B (49.5%) and a second epidemic of subgroup A (44.9%). 19 (38%) were rotavirus nosocomial infections and 5 (2.2%) were RSV nosocomial infections. The majority of the nosocomial infections occurred before the age of one year and particularly before the age of 6 months (42.2% for rotavirus, 60% for RSV). In comparison to community-acquired infections, children with rotavirus nosocomial infections were younger (9 months versus 12.5 months) which was the opposite for RSV nosocomial infections (10.8 months versus 6.5 months). The sex-ratio of children with community-acquired infections was 2.1 that was not reported in nosocomial infections. The length of stay in hospital was always longer in nosocomial infections (11.7 days versus 3.6 days for rotavirus; 38.8 days versus 4.8 days for RSV). Diarrhea (p = 0.007) and vomiting (p = 0.013) for enteric infections and wheezing (p = 0.02) for respiratory infections were more often observed in community-acquired infections. This study emphasizes the frequency and the consequences of rotavirus and RSV nosocomial infections in paediatric wards and the importance of the hygienic rules to prevent these infections.


Idiopathic Subglottic and Tracheal Stenosis: A Survey of the Patient Experience.
To report and compare patients' experiences with acquired subglottic stenosis (AS) versus idiopathic subglottic and tracheal stenosis (ISTS). A survey was made available to patients with AS and ISTS. Results were analyzed for inter- and intragroup differences using a 2-tailed t test. The study included 160 survey participants (AS n = 28; ISTS n = 132), with a predominance of female participants (82% AS, 98% ISTS). Acid reflux was the most prevalent comorbidity across groups (42%-43%). A significant difference in time to diagnosis was found between groups, with 32% of AS patients diagnosed within 3 months of symptom onset, compared to 2% with ISTS. A diagnosis delay greater than 18 months occurred for 58% of ISTS patients. There was no difference in treatment approach, with the most common treatment being balloon dilation, followed by laser dilation. Tracheal resection was performed in 36% of patients in both groups. Patient satisfaction with surgical outcomes was significantly higher after tracheal resection (76%) compared to other treatment modalities (39%). ISTS remains a diagnostic challenge as highlighted by the delay in diagnosis compared to AS. There appears to be no historical or symptomatic factors specific to ISTS. Additionally, patients report increased satisfaction and symptom resolution after tracheal resection.


School-based HIV/AIDS education, risky sexual behaviors, and HIV testing among high school students in the United States.
This study assessed the practical value of HIV/AIDS education among at-risk adolescents in the United States. Data were drawn from the 2013 Youth Risk Behavior Surveillance System spanning students in grades 9-12 who have engaged in sexual intercourse. A multivariate hierarchical logistic regression analysis was employed to test: (1) the individual effects of school-based HIV/AIDS education and risky sexual behaviors on the probability of HIV testing and (2) the interaction effects to estimate the degree to which the education effect varied by specific risky sexual behavior. The results indicated that students who engaged in risky sexual activities and received HIV/AIDS education were more likely to test for HIV compared to those who did not receive HIV/AIDS education. The relationship between education and HIV testing also varied according to the number of recent sexual partners. The findings have policy and practice implications. Specifically, HIV/AIDS education that promotes HIV testing should be encouraged particularly with the high-risk student population.


[Chronic high frequency deep brain stimulation of the globus pallidus internus for torsion dystonia].
Deep Brain Stimulation (DBS, chronic high frequency stimulation) is well established for Parkinson's disease and tremordominant movement disorders. Generalized dystonia is known as a type of movement disorder in which therapeutic options are very limited. A case of generalized dystonia is reported which was successfully treated by DBS in the Globus pallidus internus (GPI). A 26 years old male suffered from severe torsion dystonia of the lower limbs. The onset of symptoms was at age 7. It started with dystonia of the left foot. He very fast developed severe dystonia of the lower limbs. These complaints were initially treated by diazepam, later by baclofen (Lioresal ((R))) p.o em leader There was no L-DOPA response. Because of the rapid progression of the disease a cervical spinal cord stimulator was implanted with a transient success. Due to further progression of the disease the patient became wheelchair bounded and resistant for oral medication. Limited improvement of symptoms was achieved using continuous intrathecal administration of baclofen. Finally the patient was treated with 980 microgram intrathecal Baclofen (Lioresal ((R))) daily and up to 100 mg diazepam. Under these conditions the patient remained wheelchair bounded with severe lower limb dystonia. As an ultima ratio it was decided to treat the patient with stereotactic implantation of two electrodes (Medtronic 3387) and two neurostimulators (Medtronic ITREL ((R))II). The GPI was the bilateral target point. Intraoperative computerized tomography and ventriculography were used for target setting. Furthermore microrecordings were helpful to ensure the exact electrode positioning. Surgery was performed under sedation. Two weeks after surgery first improvement of symptoms was observed. Patient was able to stand with assistance. At the three months follow-up he could walk without assistance. Slight dystonic movement of the left ankle was the only remaining symptom under stimulation. The oral medication has been continuously reduced. After 6 months it was stopped. The intrathecal administered baclofen was diminished to 250 microgram daily. At the 24 months follow-up the effect of stimulation remained unchanged. However high stimulation parameters are required to maintain an optimal effect (3,5 V, 400 microseconds 145 Hz for both sides). Deep Brain Stimulation of the Globus Pallidus internus is an alternative approach for severe cases of generalized dystonia.


Limb bone allometry during postnatal ontogeny in non-avian dinosaurs.
Although the interspecific scaling of tetrapods is well understood, remarkably little work has been done on the ontogenetic scaling within tetrapod species, whether fossil or recent. Here the ontogenetic allometry of the femur, humerus, and tibia was determined for 23 species of non-avian dinosaur by regressing log-transformed length against log-transformed circumference for each bone using reduced major axis bivariate regression. The femora of large theropod species became more robust during ontogeny, whereas growth in the femora of sauropodomorphs and most ornithischians was not significantly different from isometry. Hadrosaur hindlimb elements became significantly more gracile during ontogeny. Scaling constants were higher in all theropods than in any non-theropod taxa. Such clear taxonomically correlated divisions were not evident in the ontogenetic allometry of the tibia and hindlimb bones did not scale uniformly within larger taxonomic groups. For taxa in which the ontogenetic allometry of the humerus was studied, only Riojasaurus incertus exhibited a significant departure from isometry. Using independent contrasts, the regression of femoral allometry against the log of adult body mass was found to have a significant negative correlation but such a relationship could not be established for other limb elements or growth parameters, mainly due to the small sample size. The intraspecific scaling patterns observed in dinosaurs and other amniotes do not support earlier hypotheses that intraspecific scaling differs between endothermic and ectothermic taxa.


Accelerated Bioprocess Development of Endopolygalacturonase-Production with Saccharomyces cerevisiae Using Multivariate Prediction in a 48 Mini-Bioreactor Automated Platform.
Mini-bioreactor systems enabling automatized operation of numerous parallel cultivations are a promising alternative to accelerate and optimize bioprocess development allowing for sophisticated cultivation experiments in high throughput. These include fed-batch and continuous cultivations with multiple options of process control and sample analysis which deliver valuable screening tools for industrial production. However, the model-based methods needed to operate these robotic facilities efficiently considering the complexity of biological processes are missing. We present an automated experiment facility that integrates online data handling, visualization and treatment using multivariate analysis approaches to design and operate dynamical experimental campaigns in up to 48 mini-bioreactors (8⁻12 mL) in parallel. In this study, the characterization of Saccharomyces cerevisiae AH22 secreting recombinant endopolygalacturonase is performed, running and comparing 16 experimental conditions in triplicate. Data-driven multivariate methods were developed to allow for fast, automated decision making as well as online predictive data analysis regarding endopolygalacturonase production. Using dynamic process information, a cultivation with abnormal behavior could be detected by principal component analysis as well as two clusters of similarly behaving cultivations, later classified according to the feeding rate. By decision tree analysis, cultivation conditions leading to an optimal recombinant product formation could be identified automatically. The developed method is easily adaptable to different strains and cultivation strategies, and suitable for automatized process development reducing the experimental times and costs.


Surgical treatment of giant-cell tumor of the spine. The experience at the Istituto Ortopedico Rizzoli.
We reviewed the cases of nine patients with a giant-cell tumor of the vertebrae. All segments of the spine can be affected by the tumor, but there was a predilection for the lumbar segments in our series. Pain was present in all patients. The maximum duration before the diagnosis was made was three years and the minimum, forty-five days (average, 12.2 months). In six patients a neural deficit was also present. One patient was treated many years ago by radiation therapy alone; three patients were treated by decompressive laminectomy; two, by excision of the lesion and postoperative radiation therapy; and three patients underwent lesional but extensive excision as well as arthrodesis without any preoperative or postoperative radiation therapy. We have obtained good results with the latter treatment; after follow-ups of sixty, twenty-six, and twenty-four months in three patients the pain and the neural symptoms subsided, while roentgenographic examination showed no evidence of local recurrence. In all patients the autogenous bone grafts appeared to be incorporated, without any secondary deformity. We concluded that, due to the development of better surgical techniques, the surgical approach is probably the best modern treatment for a giant-cell tumor located in the spine.


The intersection of social determinants of health and family care of people living with Alzheimer's disease and related dementias: A public health opportunity.
In this Perspective article, we highlight current research to illustrate the intersection of social determinants of health (SDOHs) and Alzheimer's disease and related dementia (ADRD) caregiving. We then outline how public health can support ADRD family caregivers in the United States. Emerging research suggests that family care for persons with ADRD is influenced by SDOHs. Public health actions that address these intersections such as improved surveillance and identification of ADRD caregivers; building and enhancing community partnerships; advancing dementia-capable health care and related payment incentives; and reducing the stigma of dementia and ADRD caregiving can potentially enhance the health and well-being of dementia caregivers. By engaging in one or all of these actions, public health practitioners could more effectively address the myriad of challenges facing ADRD caregivers most at risk for emotional, social, financial, psychological, and health disruption.


HCV-induced miR146a controls SOCS1/STAT3 and cytokine expression in monocytes to promote regulatory T-cell development.
Host innate and adaptive immune responses must be tightly regulated by an intricate balance between positive and negative signals to ensure their appropriate onset and termination while fighting pathogens and avoiding autoimmunity; persistent pathogens may usurp these regulatory machineries to dampen host immune responses for their persistence in vivo. Here, we demonstrate that miR146a is up-regulated in monocytes from hepatitis C virus (HCV)-infected individuals compared to control subjects. Interestingly, miR146a expression in monocytes without HCV infection increased, whereas its level in monocytes with HCV infection decreased, following Toll-like receptor (TLR) stimulation. This miR146a induction by HCV infection and differential response to TLR stimulation were recapitulated in vitro in monocytes co-cultured with hepatocytes with or without HCV infection. Importantly, inhibition of miR146a in monocytes from HCV-infected patients led to a decrease in IL-23, IL-10 and TGF-β expressions through the induction of suppressor of cytokine signalling 1 (SOCS1) and the inhibition of signal transducer and activator transcription 3 (STAT3), and this subsequently resulted in a decrease in regulatory T cells (Tregs) accumulated during HCV infection. These results suggest that miR146a may regulate SOCS1/STAT3 and cytokine signalling in monocytes, directing T-cell differentiation and balancing immune clearance and immune injury during chronic viral infection.


Information management in the Australian aged care setting.
Information management systems and processes have an impact on quality and safety of care in any setting and particularly in the complex care setting of aged care. Few studies have comprehensively examined information management in the Australian aged care setting. To (i) critically analyse and synthesize evidence related to information management in aged care, (ii) identify aged care data collection frameworks and (iii) identify factors impacting information management. An integrative review of Australian literature published between March 2008 and August 2014 and data collection frameworks concerning information management in aged care were carried out. There is limited research investigating the information-rich setting of aged care in Australia. Electronic systems featured strongly in the review. Existing research focuses on residential settings with community aged care largely absent. Information systems and processes in the setting of aged care in Australia are underdeveloped and poorly integrated. Data quality and access are more problematic within community aged care than residential care settings. The results of this review represent an argument for a national approach to information management in aged care to address multiple stakeholder information needs and more effectively support client care.


Periodontal Microbiological Status Influences the Occurrence of Cyclosporine-A and Tacrolimus-Induced Gingival Overgrowth.
Immune suppressed renal transplant patients are more prone to developing oral tissue alterations due to medications associated with a pleiotropic set of side effects involving the oral cavity. Drug-induced gingival overgrowth (DIGO) is the most commonly encountered side effect resulting from administration of calcineurin inhibitors such as cyclosporine-A (CsA), the standard first-line treatment for graft rejection prevention in transplant patients. Pathogenesis of gingival overgrowth (GO) is determined by the interrelation between medications and a pre-existing inflammatory periodontal condition, the main modifiable risk factor. Severity of gingival hyperplasia clinical manifestation is also related to calcium channel blocker association, frequently provided in addition to pharmacological therapy of transplant recipients. Specifically, nifedipine-induced enlargements have a higher prevalence rate compared to amlodipine-induced enlargements; 47.8% and 3.3% respectively. Available epidemiological data show a gender difference in prevalence, whereby males are generally more frequently affected than females. The impact of GO on the well-being of an individual is significant, often leading to complications related to masticatory function and phonation, a side effect that may necessitate switching to the tacrolimus drug that, under a similar regimen, is associated with a low incidence of gingival lesion. Early detection and management of GO is imperative to allow patients to continue life-prolonging therapy with minimal morbidity. The purpose of this study was threefold: firstly, to determine the prevalence and incidence of GO under the administration of CsA and Tacrolimus; secondly, to assess the correlation between periodontal status before and after periodontal therapy and medications on progression or recurrence of DIGO; and finally, to analyse the effect of immunosuppressant in association to the channel blocker agents on the onset and progression of gingival enlargement. We compared seventy-two renal transplant patients, including 33 patients who were receiving CsA, of which 25% were also receiving nifedipine and 9.72% also receiving amlodipine, and 39 patients who were receiving tacrolimus, of which 37.5% were also receiving nifedipine and 5.55% also receiving amlodipine, aged between 35 and 60 years. Medical and pharmacological data were recorded for all patients. Clinical periodontal examination, in order to establish the inflammatory status and degree of gingival enlargement, was performed at baseline (T0), 3 months (T1), 6 months (T2), and 9 months (T3). All patients were subjected to periodontal treatment. Statistically significant correlation between the reduction of the mean value of periodontal indices and degree of gingival hyperplasia at the three times was revealed. The prevalence of GO in patients taking cyclosporine was higher (33.3%) in comparison with those taking tacrolimus (14.7%). In accordance with previous studies, this trial highlighted the clinical significance of the pathological substrate on stimulating drug-induced gingival lesion, confirming the key role of periodontal inflammation in pathogenesis of gingival enlargement, but did not confirm the additional effect of calcium-channel blocker drugs in inducing gingival enlargement.


Epistatic effects between two genes in the renin-angiotensin system and systolic blood pressure and coronary artery calcification.
Coronary artery calcification (CAC) is an important indicator of future coronary artery disease events. Since elevated blood pressure (BP) is an important predictor of CAC, genetic polymorphisms in the renin-angiotensin system and their interaction may play a role in explaining CAC quantity variation. As part of the Epidemiology of Coronary Artery Calcification Study, 166 asymptomatic women and 166 asymptomatic men were genotyped for the insertion/deletion polymorphism in the angiotensin-converting enzyme (ACE) gene and the -6 promoter polymorphism of the angiotensinogen (AGT) gene. We used a novel method to detect gene-gene interaction and compared it to the standard two-way analysis of variance (ANOVA) method. Based on a two-way ANOVA model, there was no evidence for epistasis for either systolic BP or CAC in either men or women. However, using a novel method, we found evidence of significant gene-gene interaction in systolic BP in men and gene-gene interaction in both systolic BP levels and CAC quantity in women. Our study demonstrates that new methods of assessing epistasis maybe important in understanding the complex genetics of systolic blood pressure as well as subclinical coronary atherosclerosis.


On the recognition of printed characters of any font and size.
We describe the current state of a system that recognizes printed text of various fonts and sizes for the Roman alphabet. The system combines several techniques in order to improve the overall recognition rate. Thinning and shape extraction are performed directly on a graph of the run-length encoding of a binary image. The resulting strokes and other shapes are mapped, using a shape-clustering approach, into binary features which are then fed into a statistical Bayesian classifier. Large-scale trials have shown better than 97 percent top choice correct performance on mixtures of six dissimilar fonts, and over 99 percent on most single fonts, over a range of point sizes. Certain remaining confusion classes are disambiguated through contour analysis, and characters suspected of being merged are broken and reclassified. Finally, layout and linguistic context are applied. The results are illustrated by sample pages.


Cellular and viral factors regulate the varicella-zoster virus gE promoter during viral replication.
Varicella-zoster virus (VZV) glycoprotein E (gE) is essential for viral replication and is involved in cell-to-cell spread, secondary envelopment, and entry. We created a set of mutations in the gE promoter to investigate the role of viral and cellular transcriptional factors in regulation of the gE promoter. Deletion or point mutation of the two Sp1 sites in the gE promoter abolished Sp1 binding and IE62-mediated transactivation of the gE promoter in vitro. Incorporation of the deletion or the point mutations disrupting both of the Sp1 binding sites into the VZV genome was not compatible with viral replication. A point mutation altering the atypical Sp1 binding site was lethal, while altering the second site impaired VZV replication significantly, indicating functional differences between the two Sp1 binding sites. Deletions in the gE promoter that abolished putative binding sites for cellular transcriptional factors other than Sp1, identified by bioinformatics analysis, were inserted in the VZV genome. Replication of the viruses with mutations of the gE promoter did not differ from control recombinants in melanoma cells or primary human tonsil T cells in vitro. These deletions did not affect infection of human skin xenografts in SCIDhu mice. These results indicate that Sp1 is required for IE62-mediated transactivation of the gE promoter and that this transcriptional factor appears to be the only cellular factor essential for regulation of the gE promoter.


Testosterone effects on functional amygdala lateralization: A study in adolescent transgender boys and cisgender boys and girls.
The influence of testosterone on the development of human brain lateralization has been subject of debate for a long time, partly because studies investigating this are necessarily mostly correlational. In the present study we used a quasi-experimental approach by assessing functional brain lateralization in trans boys (female sex assigned at birth, diagnosed with Gender Dysphoria, n = 21) before and after testosterone treatment, and compared these results to the functional lateralization of age-matched control groups of cisgender boys (n = 20) and girls (n = 21) around 16 years of age. The lateralization index of the amygdala was determined with functional magnetic resonance imaging (fMRI) during an emotional face matching task with angry and fearful faces, as the literature indicates that boys show more activation in the right amygdala than girls during the perception of emotional faces. As expected, the lateralization index in trans boys shifted towards the right amygdala after testosterone treatment, and the cumulative dose of testosterone treatment correlated significantly with amygdala lateralization after treatment. However, we did not find any significant group differences in lateralization and endogenous testosterone concentrations predicted rightward amygdala lateralization only in the cis boys, but not in cis girls or trans boys. These inconsistencies may be due to sex differences in sensitivity to testosterone or its metabolites, which would be a worthwhile course for future studies.


Complex sleep apnoea in congestive heart failure.
Sleep disordered breathing is common and of prognostic significance in patients with congestive heart failure (CHF). Complex sleep apnoea (complexSA) is defined as the emergence of central sleep apnoea during continuous positive airway pressure (CPAP) treatment in patients with obstructive sleep apnoea (OSA). This study aims to determine the prevalence and predictors for complexSA in patients with CHF with OSA, and to assess the effects of treatment with adaptive servoventilation. 192 patients with CHF (left ventricular ejection fraction (LVEF) ≤45%, New York Heart Association (NYHA) class ≥2) and OSA (apnoea-hypopnoea index (AHI) ≥15) were investigated using echocardiography, cardiopulmonary exercise testing, measurement of hyperoxic, hypercapnic ventilatory response, 6 min walk test and measurement of N-terminal pro-brain natriuretic peptide (NT-proBNP) prior to CPAP introduction. If patients demonstrated complexSA (AHI >15/h with <10% obstructive events) during CPAP titration, adaptive servoventilation was introduced and the investigations were repeated at 3 monthly follow-up visits. ComplexSA developed in 34 patients (18%) during CPAP titration. After adjustment for demographic and cardiac parameters, measures of CO(2) sensitivity (higher hyperoxic, hypercapnic ventilatory response) were independently associated with complexSA. Patients using adaptive servoventilation had improved AHI, NYHA class, NT-proBNP concentration, LVEF, hyperoxic, hypercapnic ventilatory response, oxygen uptake during cardiopulmonary exercise testing and the relationship between minute ventilation and the rate of CO(2) elimination (VE/Vco(2) slope) at last individual follow-up (14±4 months). There is a high prevalence of complexSA in patients with OSA and CHF, and those who develop complexSA have evidence of higher respiratory controller gain before application of CPAP. Treatment with adaptive servoventilation effectively suppressed complexSA and had positive effects on cardiac function and respiratory stability.


Alcohol use, alcohol problems, and problem behavior engagement among students at two schools in northern Mexico.
This study examined the association between alcohol-use problem severity, defined by number of DSM-IV alcohol Abuse and Dependence symptoms and frequency of alcohol use, and problem behavior engagement among Mexican students. A confidential survey was administered to 1229 students in grades 7-12 at two schools in a northern border city in Mexico. Youths were categorized into five groups based on their alcohol use frequency and symptoms of DSM-IV alcohol Abuse and Dependence, specifically: no lifetime alcohol use, lifetime alcohol use but none in the past year, past year alcohol use, one or two alcohol Abuse or Dependence symptoms, and three or more alcohol Abuse or Dependence symptoms. The association between five levels of alcohol-use problem severity and three problem behaviors, lifetime marijuana use, lifetime sexual intercourse, and past year arrest/law trouble, was examined using chi-square or Fisher's exact tests. Several alcohol-use problem severity categories were significantly different with respect to rates of lifetime marijuana use, lifetime sexual intercourse, and past year arrest/law trouble. Higher alcohol-use problem severity was associated with greater endorsement of problem behaviors. Knowing about variations in adolescent alcohol use and alcohol problems may be instrumental in determining if youths are also engaging in a range of other risk behaviors. Considering varying levels of alcohol use and alcohol problems is important for effective targeted prevention and treatment interventions.


Your next patient does not speak English: translation and interpretation in today's busy office.
Today's advanced practice nurse needs to know the pitfalls, problems, and risks that can occur when providing health care to patients who come from a different culture and who speak a different language. When appropriate translation and interpretation services are available there is an increased likelihood of patient compliance, solid patient-provider relationships, and improved patient outcomes. Even though the research indicates that a professional translator is needed, excellent care is possible using nonprofessional translators if the advanced practice nurse understands what needs to be done to facilitate communication and can assess when effective communication is not occurring.


The corticomotor representation of upper limb muscles in writer's cramp and changes following botulinum toxin injection.
Transcranial magnetic stimulation was used to investigate the properties of the corticomotor pathway and to map the primary motor cortex projection to hand and forearm muscles during a sustained isometric contraction in a group of subjects with writer's cramp of varying duration. Corticomotor threshold, motor evoked potential amplitude and latency, and silent-period duration were normal on both sides in all subjects. The maps of the corticomotor projection were displaced relative to normal in all subjects, and in some cases were distorted in shape, with extensions of the lateral borders and the emergence of almost discrete secondary motor areas. The degree of map distortion and displacement was greatest in subjects with long-standing writer's cramp (> 5 years), and was bilateral in some cases. Injection of botulinum toxin into affected muscles demonstrated that the alterations in map topography were not fixed, and could be temporarily reversed during the period when the clinical effects of the injection were greatest, with the maps returning to their original positions as the effects of the injection wore off. It is concluded from this study that there are slowly evolving reorganizational changes in the primary motor cortex in writer's cramp, and that these changes may be secondary to altered afferent inputs from both clinically affected and unaffected muscles.


A rapid and simple method for distinguishing colonies of proteus from those of Salmonella and Shigella.
A rapid and simple method is described by which colonies of Proteus can be distinguished from those of Salmonella and Shigella and other non-lactose-fermenting organisms growing on MacConkey's agar or desoxycholate citrate agar. The method is based on the ability of Proteus to produce urease constitutively. The enzyme was detected by the degradation of urea by the inoculum, thereby creating an alkaline reaction on pH-indicator paper.


Pancreatic trypsin activates human promatrix metalloproteinase-2.
In contrast to the prevalent view in the literature hitherto, the present study shows that pancreatic trypsin can activate human promatrix metalloproteinase-2 (proMMP-2). It is shown that trypsin's ability to activate proMMP-2 is dependent on various environmental factors such as the level of exogenously added Ca(2+) and Brij-35, temperature, as well as trypsin concentration. The activation occurred as a sequential processing of the proenzyme, initially generating an active 62kDa species. This was followed by successive truncation of the C-terminal domain, giving rise to active species of 56kDa, 52kDa and 50kDa. Tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) prevented the trypsin-mediated C-terminal truncation, without affecting the generation of the 62kDa species, while the presence of EDTA increased the rate of the trypsin-mediated activation of proMMP-2. MALDI-TOF MS analysis of the 50kDa form indicated that trypsin generated active forms with either Lys87 or Trp90 as the N-terminal residue and Arg538 as a C-terminal residue. The trypsin-activated MMP-2 was active in solution against both synthetic and physiologic substrates, and the steady-state kinetic coefficients k(cat), K(m) and k(cat)/K(m) were determined for the enzyme activated either by APMA, membrane-type 1 matrix metalloproteinase (MT1-MMP) or trypsin. The trypsin-activated MMP-2 exhibited slightly lower k(cat) and k(cat)/K(m) values as well as a slightly higher K(i) value against TIMP-1 compared to the enzyme activated by APMA or MT1-MMP. Docking studies of TIMP-1 revealed that the slightly weaker binding of the inhibitor to the trypsin-activated MMP-2 could be attributed to its shorter N terminus (Lys87/Trp90 versus Tyr81), as Phe83 and Arg86 interacted directly with the inhibitor. Our results suggest that the trypsin-activated MMP-2 possesses the catalytic and regulatory potential to be of significance in vivo.


A Breastfeeding Relaxation Intervention Promotes Growth in Late Preterm and Early Term Infants: Results from a Randomized Controlled Trial.
Breastfeeding involves signaling between mother and offspring through biological (breast milk) and behavioral pathways. This study tested this by examining the effects of a relaxation intervention in an understudied infant population. Breastfeeding mothers of late preterm (340/7-366/7 weeks) and early term (370/7-386/7 weeks) infants were randomized to the relaxation group (RG, n = 35), where they were asked to listen to a meditation recording while breastfeeding from 3 weeks post-delivery, or the control group (CG, n = 37) where no intervention was given. Primary outcomes-maternal stress and infant weight-were assessed at 2-3 (baseline) and 6-8 weeks post-delivery. Secondary outcomes included infant length, infant behavior, maternal verbal memory, salivary cortisol, and breast milk composition. Infants in the RG had significantly higher change in weight-for-age Z-score compared to those in CG (effect size: 0.4; 95% CI: 0.09, 0.71; p = 0.01), and shorter crying duration [RG: 5.0 min, 0.0-120.0 vs. CG: 30.0 min, 0.0-142.0; p = 0.03]. RG mothers had greater reduction in cortisol (effect size: -0.08 ug/dL, 95% CI -0.15, -0.01; p = 0.03) and better maternal verbal learning score (effect size: 1.1 words, 95% CI 0.04, 2.1; p = 0.04) than CG mothers, but did not differ in stress scores. A simple relaxation intervention during breastfeeding could be beneficial in promoting growth of late preterm and early term infants. Further investigation of other potential biological and behavioral mediators is warranted.


Categorization of adverse drug reactions in electronic health records.
The purpose of this study was to evaluate the quality of adverse drug reaction (ADR) documentation in a state-wide electronic health record (EHR), and to assess the impact of the interface design on documentation accuracy and ability to provide decision support. Data were extracted from 43 011 unique records in a state-wide electronic health record in South Australia, Australia. Information obtained included ADR coding as allergy or intolerance, allergen name, reaction, and occupation of those entering data. Categorization into drug allergy or intolerance was assessed for accuracy. Reactions were entered predominantly by nurses (60.1%), also by doctors (31.0%) and pharmacists (6.1%). Of 27 314 reactions, 86.5% were coded as allergy and 13.5% as intolerance. The majority (78.2%) described reactions to drugs (as opposed to food, environmental or contact allergens), predominantly chosen from the drug database (96.4%). Many entries used free text for the reaction description (27.4%). Terms found in the predefined list under the allergy heading were more likely to be categorized as allergy, even when the mechanism was pharmacological intolerance. Only 45.1% (n = 1671/3705) of reactions consistent with intolerance (eg, "nausea," "diarrhea") were correctly categorized as such, although categorization by pharmacists was more accurate (P < .0001). These data suggest that ADR categorization as allergy or intolerance is influenced by the EHR design. The obligatory classification of ADRs into allergy or intolerance was not well understood and does not appear to have practical benefit.


[Acupuncture therapy in the treatment of patients with bronchial asthma].
Erythron membrane impairment was investigated using membrane -active drugs (obsidan, delagil, morphium, ethanol) to specify indications to acupuncture in bronchial asthma (BA). The patients were studied during the treatment and followed up for a year. It was found that both immediate and long-term results of acupuncture were related to patterns of the membrane impairment. BA patients with a sharp, greater than 1.5 fold diminution of microcyte count upon delagil test should be assigned to repeated courses of acupuncture during a year. To monitor the treatment effect, it is recommended to define osmotic resistance of the red blood cells in obsidan test in addition to clinicofunctional indices.


Global trajectories of the long-term decline of coral reef ecosystems.
Degradation of coral reef ecosystems began centuries ago, but there is no global summary of the magnitude of change. We compiled records, extending back thousands of years, of the status and trends of seven major guilds of carnivores, herbivores, and architectural species from 14 regions. Large animals declined before small animals and architectural species, and Atlantic reefs declined before reefs in the Red Sea and Australia, but the trajectories of decline were markedly similar worldwide. All reefs were substantially degraded long before outbreaks of coral disease and bleaching. Regardless of these new threats, reefs will not survive without immediate protection from human exploitation over large spatial scales.


[Psychosocial care following the firework disaster in Enschede; the lessons from the Bijlmer airline disaster].
When the psychosocial-care scheme for victims of the firework explosion in Enschede, the Netherlands (2000) was set up, lessons learned from the Bijlmer airline disaster (Amsterdam 1992) were put into practice. The aftermath of this incident showed that psychological and physical health problems can still occur many years later. The main failure of the aftercare of the Bijlmer disaster lay in the coordination of aid and the monitoring of health problems. In Enschede steps were taken to redress these problems. An information and advice centre (IAC) was set up to monitor the well-being of the victims, and to provide them with information and, where necessary, assistance. It is responsible for limiting the effects of the disaster. A total of 13,000 people have consulted the IAC. A residents' association was formed. This gave the victims a common voice during the process of attempting to restore normality in their lives. A specialized mental health-care unit was founded to treat disaster-related disorders using evidence-based treatments. So far approximately 1,300 people have consulted this body. A longitudinal study has been set up to map the consequences of the disaster and to advise aid organizations. This will also give information on the extent to which these methods have been able to limit the long-term consequences.


Influence of Cooking Conditions on Carotenoid Content and Stability in Porridges Prepared from High-Carotenoid Maize.
Maize is a staple food crop in many developing countries, hence becoming an attractive target for biofortification programs toward populations at risk of micronutrient deficiencies. A South African white endosperm maize inbred line was engineered with a carotenogenic mini-pathway to generate high-carotenoid maize, which accumulates β-carotene, lutein and zeaxanthin. As maize porridge is a traditional meal for poor populations in sub-Saharan African countries, high-carotenoid maize was used as raw material to prepare different maize meals. The objective of this work was to assess the impact of popular home-cooking techniques and different cooking parameters (temperature, time and pH) on the final carotenoid content in the cooked product, using a spectrophotometric technique based on the mean absorption of carotenoids at 450 nm. Carotenoid levels were not only preserved, but also enhanced in high-carotenoid maize porridges. The carotenoid content was increased when temperatures ≤95 °C were combined with short cooking times (10-60 min). The most optimum thermal treatment was 75 °C/10 min. When treated under those conditions at pH 5, high-carotenoid maize porridges doubled the initial carotenoid content up to 88 μg/g dry weight. Regarding to cooking techniques, the highest carotenoid content was found when unfermented thin porridges were prepared (51 μg/g dry weight of high-carotenoid maize porridge). We conclude that high-carotenoid maize may contribute to enhance the dietary status of rural populations who depend on maize as a staple food.


A revised method for measuring distraction by tactile stimulation.
Sensory hypersensitivity (SH) refers to the tendency to attend to subtle stimuli, to persist in attending to them, and to find them noxious. SH is relatively common in several developmental disorders including Tourette Syndrome and Chronic Tic Disorder (TS/CTD). This study was an attempt to quantify the extent to which a mild tactile stimulus distracts one's attention in TS/CTD. Fourteen adults with TS/CTD and 14 tic-free control subjects completed questionnaires regarding SH and ADHD, and TS/CTD subjects completed self-report measures of current and past tic disorder symptoms and of current obsessions and compulsions. All subjects performed a sustained attention choice reaction time task during alternating blocks in which a mildly annoying stimulus (von Frey hair) was applied to the ankle ("ON") or was not applied ("OFF"). We present here the clinical and cognitive task data for each subject.


The need to know: experiences of critically ill patients.
Critically ill patients vary in their memories of their experience in the intensive care unit. Some have little recall and need to learn about their critical illness. Others have more vivid memories of their experiences, some of which were extremely unpleasant. Patients' not knowing what was happening may have exacerbated the unpleasant experiences. To elicit the experience of knowing for critically ill patients and to explore the differences in perceptions between patients who were intubated and those who were not intubated during the illness. Grounded theory was used to explore the meaning of knowing and not knowing and the process by which knowing occurs. Unstructured interviews were done with 14 patients. Knowing had 2 phases: the need to know (1) during and (2) after the critical illness. The first phase had 3 facets: needing information, needing to be oriented, and having confusing perceptions. The second phase had 2 facets: needing information about what had happened and piecing together events. Many experiences with knowing during and after a critical illness were similar for both intubated and nonintubated patients. The main difference was the intensity of the experience in some categories. Critically ill patients have a strong need to know throughout and after their time in the intensive care unit. Nurses must address this need for constant reorientation to the past and present in these patients. In addition, adequate nursing staff must be available for these patients.


Honey as an antioxidant therapy to reduce cognitive ageing.
This paper reviews the potential role of honey as a therapeutic antioxidant to reduce oxidative stress and improve cognitive ageing. All articles indexed to PubMed Central (PMC) were searched using the following key words: honey, antioxidant, memory and ageing. Honey is a natural insect-derived product with therapeutic, medicinal and nutritional values. Antioxidant properties of honey quench biologically-circulating reactive oxygen species (ROS) and counter oxidative stress while restoring the cellular antioxidant defense system. Antioxidant properties of honey may complement its nootropic effects to reduce cognitive ageing.


Plasmodium fallax: phagocytosis of exoerythrocytic stages in tissue culture.
Wandering phagocytes in tissue cultures were attracted to the exoerythrocytic stages, both intracellular and extracellular, of Plasmodium fallax. They phagocytized free merozoites or schizonts that had been freed from host cells. They attempted to phagocytize large intracellular parasites.


Changes In Hospital Utilization Three Years Into Maryland's Global Budget Program For Rural Hospitals.
In a substantial shift in payment policy, the State of Maryland implemented a global budget program for acute care hospitals in 2010. Goals of the program include controlling hospital use and spending. Eight rural hospitals entered the program in 2010, while urban and suburban hospitals joined in 2014. Prior analyses, which focused on urban and suburban hospitals, did not find consistent evidence that Maryland's program had contributed to changes in hospital use after two years. However, these studies were limited by short follow-up periods, may have failed to isolate impacts of Maryland's payment change from other state trends, and had limited generalizability to rural settings. To understand the effects of Maryland's global budget program on rural hospitals, we compared changes in hospital use among Medicare beneficiaries served by affected rural hospitals versus an in-state control population from before to after 2010. By 2013-three years after the rural program began-there were no differential changes in acute hospital use or price-standardized hospital spending among beneficiaries served by the affected hospitals, versus the within-state control group. Our results suggest that among Medicare beneficiaries, global budgets in rural Maryland hospitals did not reduce hospital use or price-standardized spending as policy makers had anticipated.


Purification and characterization of a medium chain acyl-coenzyme A synthetase.
Glycine conjugation is an important route of detoxification of many xenobiotic and endogenous carboxylic acids. A medium chain acyl-coenzyme A synthetase that catalyzes the first reaction of glycine conjugation was purified from bovine liver mitochondria by chromatographies on anion exchange, hydroxylapatite, affinity, and finally by gel filtration. The purified enzyme not only conjugates medium chain fatty acids, but also aromatic and arylacetic acids. The highest activity was shown with hexanoic acid. High activities were observed for benzoic acid derivatives with large alkyl and alkoxyl groups in the para- or meta-positions of the benzene ring. Ortho-substituted derivatives exhibited no activity. The enzyme was inhibited by iodoacetamide and salicylic acid, and activated by albumin. Salicylic acid was a competitive inhibitor of the enzyme, with an apparent Ki value of 37 microM. Enzyme activity increased 74% when the pH was raised from 7 to 10. Molecular weight of the purified medium chain acyl-coenzyme A synthetase was 65.5 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.


Plasmonic hot electron transport drives nano-localized chemistry.
Nanoscale localization of electromagnetic fields near metallic nanostructures underpins the fundamentals and applications of plasmonics. The unavoidable energy loss from plasmon decay, initially seen as a detriment, has now expanded the scope of plasmonic applications to exploit the generated hot carriers. However, quantitative understanding of the spatial localization of these hot carriers, akin to electromagnetic near-field maps, has been elusive. Here we spatially map hot-electron-driven reduction chemistry with 15 nm resolution as a function of time and electromagnetic field polarization for different plasmonic nanostructures. We combine experiments employing a six-electron photo-recycling process that modify the terminal group of a self-assembled monolayer on plasmonic silver nanoantennas, with theoretical predictions from first-principles calculations of non-equilibrium hot-carrier transport in these systems. The resulting localization of reactive regions, determined by hot-carrier transport from high-field regions, paves the way for improving efficiency in hot-carrier extraction science and nanoscale regio-selective surface chemistry.


Integrating the Combined Sagittal Index Reduces the Risk of Dislocation Following Total Hip Replacement.
The aims of this matched cohort study were to (1) assess differences in spinopelvic characteristics between patients who sustained a dislocation after total hip arthroplasty (THA) and a control group without a dislocation, (2) identify spinopelvic characteristics associated with the risk of dislocation, and (3) propose an algorithm including individual spinopelvic characteristics to define an optimized cup orientation target to minimize dislocation risk. Fifty patients with a history of THA dislocation (29 posterior and 21 anterior dislocations) were matched for age, sex, body mass index (BMI), index diagnosis, surgical approach, and femoral head size with 200 controls. All patients underwent detailed quasi-static radiographic evaluations of the coronal (offset, center of rotation, and cup inclination/anteversion) and sagittal (pelvic tilt [PT], sacral slope [SS], pelvic incidence [PI], lumbar lordosis [LL], pelvic-femoral angle [PFA], and cup anteinclination [AI]) reconstructions. The spinopelvic balance (PI - LL), combined sagittal index (CSI = PFA + cup AI), and Hip-User Index were determined. Parameters were compared between the control and dislocation groups (2-group analysis) and between the controls and 2 dislocation groups identified according to the direction of the dislocation (3-group analysis). Important thresholds were determined from receiver operating characteristic (ROC) curve analyses and the mean values of the control group; thresholds were expanded incrementally in conjunction with running-hypothesis tests. There were no coronal differences, other than cup anteversion, between groups. However, most sagittal parameters (LL, PT, CSI, PI - LL, and Hip-User Index) differed significantly. The 3 strongest predictors of instability were PI - LL >10° (sensitivity of 70% and specificity of 65% for instability regardless of direction), CSIstanding of <216° (posterior instability), and CSIstanding of >244° (anterior instability). A CSI that was not between 205° and 245° on the standing radiograph (CSIstanding) was associated with a significantly increased dislocation risk (odds ratio [OR]: 4.2; 95% confidence interval [CI]: 2.2 to 8.2; p < 0.001). In patients with an unbalanced and/or rigid lumbar spine, a CSIstanding that was not 215° to 235° was associated with a significantly increased dislocation risk (OR: 5.1; 95% CI: 1.8 to 14.9; p = 0.001). Spinopelvic imbalance (PI - LL >10°) determined from a preoperative standing lateral spinopelvic radiograph can be a useful screening tool, alerting surgeons that a patient is at increased dislocation risk. Measurement of the PFA preoperatively provides valuable information to determine the optimum cup orientation to aim for a CSIstanding of 205° to 245°, which is associated with a reduced dislocation risk. For patients at increased dislocation risk due to spinopelvic imbalance (PI - LL >10°), the range for the optimum CSI is narrower. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Bacterial colonisation of leg ulcers and its effect on the success rate of skin grafting.
There is little information on the immediate and long-term results of skin grafting to chronic lower limb ulcers. Our experience in their management had led us to analyse, retrospectively, the results of split thickness skin grafts applied to lower limb ulcers in 88 consecutive patients. Graft take has been related to bacterial growth from ulcer swabs taken on admission, preoperatively and postoperatively. Follow-up was for a median of 18 months. Initial graft take varied from 20% to 100% (median 85%). Bacterial flora grown from the ulcer swabs varied with the duration of the ulcer and the treatment. Analysis by bacterial type has shown that Staphylococcus aurcus and Pseudomonas significantly reduced skin graft healing. Overall, 90% of these ulcers had healed with a median of 6 weeks' in-patient treatment. Examination of the swab results from the 8 ulcers that were slow to heal postoperatively and the 8 ulcers that recurred 6 days to 8 months after discharge from hospital revealed that 15 out of 16 (94%) grew S. aurcus; none had Pseudomonas isolated from them. After eighteen months 8% of these ulcers remain active. Aetiology appears important as this figure is 6% for limbs affected by venous disease only, 13.3% for limbs with arterial disease only and 13.6% for limbs with both venous and arterial disease.


Continuity of care in the ambulatory sector and hospital admissions among patients with heart failure in Germany.
Heart failure is one of the most cost-intensive chronic diseases and the most common cause of hospitalization. More than 60% of the treatment costs of heart failure are incurred in the inpatient sector in Germany. However, hospital admissions due to heart failure are considered to be potentially avoidable through effective and continuous ambulatory care. Our aim is to examine whether continuity in ambulatory care is associated with hospitalizations due to heart failure. Using insurance claims data from Germany's biggest statutory health insurance company, we defined three measures of continuity of care: Continuity of Care Index (COCI), Usual Provider Index (UPC) and the Sequential Continuity Index (SECON). We analyzed whether these measures are associated with hospitalization due to heart failure using separate logistic regression models. We controlled for a wide range of covariates such as sex, age and the Charlson comorbidity index. Data of 382 118 heart failure patients were included in the analyses. Index values range from 0.77 to 0.89. Results of logistic regression analyses indicate that the continuity indices COCI, UPC and SECON based on visits to general practitioners (GPs), cardiologists and internists are negatively associated with the probability of hospitalization whereas of the continuity indices based on GP visits only SECON is significantly associated with hospitalization. The results indicate that the overall continuity in the ambulatory sector is high for heart failure patients in Germany. Public policy should, nevertheless, focus on increasing sequential continuity of specialist and generalist ambulatory care as this was found to be significantly associated with a reduced likelihood of hospitalization.


Staging anti-inflammatory therapy in Alzheimer's disease.
The use of non-steroidal anti-inflammatory drugs (NSAIDs) in Alzheimer's disease (AD) is controversial because conclusions from numerous epidemiological studies reporting delayed onset of AD in NSAID users have not been corroborated in clinical trials. The purpose of this personal view is to revise the case for NSAIDs in AD therapeutics in light of: (i) the last report from the only primary prevention trial in AD, ADAPT, which, although incomplete, points to significant protection in long-term naproxen users, and (ii) the recently proposed dynamic model of AD evolution. The model contends that there is a clinical silent phase in AD that can last up to 20 years, the duration depending on life style habits, genetic factors, or cognitive reserve. The failure of many purported disease-modifying drugs in AD clinical trials is forcing the view that treatments will only be efficacious if administered pre-clinically. Here we will argue that NSAIDs failed in clinical trials because they are disease-modifying drugs, and they should be administered in early stages of the disease. A complete prevention trial in cognitively normal individuals is thus called for. Further, the shift of anti-inflammatory treatment to early stages uncovers a knowledge void about the targets of NSAIDs in asymptomatic individuals. AD researchers have mostly relied on post-mortem analysis of Aβ plaque-laden brains from demented patients or animal models, thus drawing conclusions about AD pathogenesis based on late symptoms. We will discuss evidence in support that defective, not excessive, inflammation underlies AD pathogenesis, that NSAIDs are multifunctional drugs acting on inflammatory and non-inflammatory targets, and that astrocytes and microglia may play differing roles in disease progression, with an emphasis of ApoEε4 as a key, undervalued target of NSAIDs. According to a meta-analysis of epidemiological data, NSAIDs afford an average protection of 58%. If this figure is true, and translated into patient numbers, NSAID treatment may revive as a worth pursuing strategy to significantly reduce the socio-economical burden imposed by AD.


Perceptions about female sexuality among young Pakistani men presenting to family physicians at a teaching hospital in Karachi.
To study the perceptions about female sexuality among young Pakistani men, presenting to family physicians at a teaching hospital in Karachi, Pakistan. A questionnaire based prevalence study. Questionnaire administered to 188 young Pakistani men, between the ages 18-30 years, who presented to family physicians, at the outpatient department of the Aga Khan University Hospital, Karachi, Pakistan. Perception among Pakistani young men about enjoyment of sexual experiences in women, whether women stop to enjoy sexual experiences during stress, menstruation, pregnancy and after menopause. Whether they are aware about "orgasm" in women and their belief in who can initiate sexual experiences, husband, wife or both. The age of the study population was uniformly distributed between 18-30 years. The majority of the respondents were professionals, with a high school or a higher level education and belonged to the middle socioeconomic group. Well over 40% of the respondents thought that sexual experiences in women in comparison to men are less enjoyable. 22% believed that women cannot enjoy sex during pregnancy while 20% thought they can't enjoy after menopause. 58% of the respondents were aware of the phenomenon of orgasm in women. 6.4% believed that the initiation of sexual experience lies with husband only. We have found a high prevalence of misconceptions about female sexuality among Pakistani young men in our study sample. We expect the situation to be more adverse in the society where education is less and people belong to the lower socio-economic class. We strongly recommend sex education of our youth.


Pay for performance in Australia: Queensland's new Clinical Practice Improvement Payment.
Following a high profile scandal relating to quality and safety of care, the health authority in the Australian state of Queensland introduced a pay for performance (P4P) component into its new hospital prospective payment system. The Clinical Practice Improvement Payment system pays hospitals for achievement of clinical process indicators. Initially the focus is on the quality of clinical processes and outcomes. Using a consensus approach involving consultation with clinicians, seven clinical indicators were adopted for 2007-2008. The first payments using pay for performance were made for work carried out up until June 2008. Although no data exist yet as to the impact of the new system, pay for performance appears to be gaining widespread, if somewhat reluctant, acceptance.


Applied aerial spectroscopy: A case study on remote sensing of an ancient and semi-natural woodland.
An area of ancient and semi-natural woodland (ASNW) has been investigated by applied aerial spectroscopy using an unmanned aerial vehicle (UAV) with multispectral image (MSI) camera. A novel normalised difference spectral index (NDSI) algorithm was developed using principal component analysis (PCA). This novel NDSI was then combined with a simple segmentation method of thresholding and applied for the identification of native tree species as well as the overall health of the woodland. Using this new approach allowed the identification of trees at canopy level, across 7.4 hectares (73,934 m2) of ASNW, as oak (53%), silver birch (37%), empty space (9%) and dead trees (1%). This UAV derived data was corroborated, for its accuracy, by a statistically valid ground-level field study that identified oak (47%), silver birch (46%) and dead trees (7.4%). This simple innovative approach, using a low-cost multirotor UAV with MSI camera, is both rapid to deploy, was flown around 100 m above ground level, provides useable high resolution (5.3 cm / pixel) data within 22 mins that can be interrogated using readily available PC-based software to identify tree species. In addition, it provides an overall oversight of woodland health and has the potential to inform a future woodland regeneration strategy.


Methodologic differences in values for M-proteins in serum, as measured by three techniques.
Accurate and reproducible measurement of M-proteins is essential for managing patients with monocional gammopathies, but serum protein electrophoresis, radial immunodiffusion, and electroimmunodiffusion yield comparatively divergent results. We have studied these differences and their causes. Sera from cases of IgG-monoclonal gammopathy, IgA-monoclonal gammopathy, and IgM-monoclonal gammopathy were assayed by each of the three techniques. Results indicated inter-method discrepancies as great as fivefold for all proteins studied. For IgG-monoclonal gammopathy, radial immunodiffusion values were less consistently so. For IgA-monoclonal gammopathy, both radial immunodiffusion and electroimmunodiffusion gave lower results than did serum protein electrophoresis. For IgM-monoclonal gammopathy, results were variable, but values by radial immunodiffusion tended to be higher than, and electroimmunodiffusion comparable to, those for serum protein electrophoresis. The differences were not correlated with protein abundance, serum freshness, immunoglobulin class, light-chain type, ultracentrifugal characteristics, or electrophoretic mobility. Clearly, values for M-protein concentration depend on the techniques used to obtain them. We postulate that subclass differences may contribute to the diversity of radial immunodiffusion results, and that for electroimmunodiffusion the fixed electrophoretic mobility of M-proteins leads to unpredictable results. We conclude that serum protein electrophoresis is the best of the three assay techniques for M-proteins.


Closing-opening wedge osteotomy to correct angular kyphotic deformity by a single posterior approach.
Seven patients with angular kyphotic deformity of the thoracic or thoracolumbar spine were treated by closing-opening wedge osteotomy using a single posterior approach. To examine the safety and efficacy of closing-opening wedge osteotomy for angular kyphosis. Correction osteotomy of severe kyphosis is a challenging operation. A two-stage operation has been commonly used: anterior release and decompression followed by posterior correction and fusion. Seven patients with angular kyphosis were treated. The apex level of kyphosis was T5 in one patient, T11 in one, and T12 in five. There was old fracture in five patients, congenital deformity in one, and neurofibromatosis in one. The first 30-35 degrees of kyphosis are corrected using the closing wedge technique with the hinge of the anterior longitudinal ligament after veretebrectomy and circumspinal decompression of the spinal cord. Then the hinge is moved posteriorly to the spinal cord and the remainder of the requisit angle of osteotomy is corrected using the opening-wedge technique (closing-opening wedge osteotomy). Spinal curvature is stabilized using posterior instrumentation and graft. Localized kyphosis was reduced from an average of 67 degrees to 18 degrees at 2.2 to 7.5 years' follow-up. Sagittal alignment from T1 to the sacrum became more physiologic than before. There were no neurologic complications. Bony fusion was achieved in all patients, and there was no correction loss. Satisfactory correction is safely performed by closing-opening wedge osteotomy with a direct visualization of the circumferentially decompressed spinal cord. Although the performance is technically laborious, it offers good correction without jeopardizing the integrity of the spinal cord.


Recurrence risk of ictal asystole in epilepsy.
To determine the recurrence risk of ictal asystole (IA) and its determining factors in people with epilepsy. We performed a systematic review of published cases with IA in 3 databases and additionally searched our local database for patients with multiple seizures simultaneously recorded with ECG and EEG and at least one IA. IA recurrence risk was estimated by including all seizures without knowledge of the chronological order. Various clinical features were assessed by an individual patient data meta-analysis. A random mixed effect logistic regression model was applied to estimate the average recurrence risk of IA. Plausibility of the calculated IA recurrence risk was checked by analyzing the local dataset with available information in chronological order. Eighty patients with 182 IA in 537 seizures were included. Recurrence risk of IA amounted to 40% (95% confidence interval [CI] 32%-50%). None of the clinical factors (age, sex, type and duration of epilepsy, hemispheric lateralization, duration of IA per patient) appeared to have a significant effect on the short-term recurrence risk of IA. When considering the local dataset only, IA recurrence risk was estimated to 30% (95% CI 14%-53%). Information whether IA coincided with symptoms (i.e., syncope) or not was given in 60 patients: 100 out of 142 IAs were symptomatic. Our data suggest that in case of clinically suspected IA, the recording of 1 or 2 seizures is not sufficient to rule out IA. Furthermore, the high short-term recurrence risk favors aggressive treatment, including pacemaker implantation if seizure freedom cannot be achieved.


Are extracapsular and intracapsular hip-fracture patients two distinct rehabilitation subpopulations?
To assess whether intracapsular and extracapsular hip fracture patients in a post-acute rehabilitation setting differ in their background characteristics and whether fracture type affects rehabilitation outcome. A retrospective cohort study. Functional Independence Measure (FIM), motor FIM (mFIM), mFIM effectiveness, length of stay (LOS), and discharge destination. Various tests assessed associations (the Mann-Whitney U, the chi-square, logistic regression), population differences (t-test), and independent predictors of discharge FIM score (multiple linear regression model). Six hundred and eighty-seven patients completed the rehabilitation program. The intracapsular hip fracture patient group was characterized by significantly higher percentages of males, higher education levels, and living with a caregiver compared with the extracapsular hip fracture patient group. Intracapsular hip fracture patients were younger, had longer latency time from fracture to surgery, exhibited higher functional levels on admission and upon discharge, higher cognitive function and shorter rehabilitation time than extracapsular hip fracture patients. Both study groups possessed similar comorbidities, rehabilitation achievements, and discharge destination. Regression analyses showed that the fracture type was not associated with discharge FIM score, nor with the probability of achieving a favorable functional gain. Post-acute extracapsular and intracapsular hip fracture patients are demographically and clinically two distinct subpopulations. Nevertheless, given additional time, extracapsular hip fracture patients will attain similar functional achievements as intracapsular hip fracture patients.Implications for rehabilitationPost-acute extracapsular and intracapsular hip fracture patients are demographically and clinically two distinct subpopulations.Given additional time, extracapsular hip fracture patients can attain similar functional achievements as intracapsular hip fracture patients.


Platelet-derived growth factors and their receptors in normal and malignant hematopoiesis.
Platelet-derived growth factors (PDGF) bind to two closely related receptor tyrosine kinases, PDGF receptor α and β, which are encoded by the PDGFRA and PDGFRB genes. Aberrant activation of PDGF receptors occurs in myeloid malignancies associated with hypereosinophilia, due to chromosomal alterations that produce fusion genes, such as ETV6-PDGFRB or FIP1L1-PDGFRA. Most patients are males and respond to low dose imatinib, which is particularly effective against PDGF receptor kinase activity. Recently, activating point mutations in PDGFRA were also described in hypereosinophilia. In addition, autocrine loops have been identified in large granular lymphocyte leukemia and HTLV-transformed lymphocytes, suggesting new possible indications for tyrosine kinase inhibitor therapy. Although PDGF was initially purified from platelets more than 30 years ago, its physiological role in the hematopoietic system remains unclear. Hematopoietic defects in PDGF-deficient mice have been reported but appear to be secondary to cardiovascular and placental abnormalities. Nevertheless, PDGF acts directly on several hematopoietic cell types in vitro, such as megakaryocytes, platelets, activated macrophages and, possibly, certain lymphocyte subsets and eosinophils. The relevance of these observations for normal human hematopoiesis remains to be established.


Antiproliferative and apoptotic effects of paeonol on human hepatocellular carcinoma cells.
Paeonol, a major phenolic component of Moutan Cortex, is known to have antitumor effects through an unknown mechanism. In this study, we tried to elucidate the anticancer effects of paeonol on human hepatocellular carcinoma (HCC) cell lines BEL-7404, SMMC-7721, and MHCC97-H in vitro. Using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, we compared the cytotoxicity of paeonol with the cytotoxicity of 5-fluorouracil (5-FU) in these three HCC cell lines. In addition, we examined the combined effect of paeonol and 5-FU over time, and found that the two compounds inhibited the proliferation of all three human HCC cell lines in a dose-dependent manner. The concentrations that inhibited the proliferation by 50% ranged from 11.39 to 56.23 mg/l for paeonol, and 6.47 to 37.87 mg/l for 5-FU. We determined that exposure to these compounds led to an upregulation of the anti-oncogene PTEN, and the downregulation of the oncogene AKT in the cell lines tested as determined by real-time quantitative reverse transcription-PCR and western blot. In addition, paeonol induced DNA fragmentation in the HCC cell line BEL-7404. These observations suggest that paeonol has the potential to be explored for use as an effective antitumor agent for HCC.


[Other causes of pulmonary arterial hypertension: pulmonary veno-occlusive disease, pulmonary capillary hemangiomatosis, porto-pulmonary hypertension, HIV- associated pulmonary arterial hypertension].
Idiopathic pulmonary arterial hypertension (PAH) is included in Group 1 of PAH classification, while pulmonary veno-occlusive disease (PVOD), pulmonary capillary hemangiomatosis (PCH), portopulmonary hypertension (PoPH) and HIV-associated PAH constitute the subgroups of Group I PAH disorders. PVOD has similar clinical presentation, hemodynamic characteristics and genetic background with PAH although main pathology is in venules and definite diagnosis is done by biopsy although not recommended due to high risk of bleeding. PCH, a rare idiopathic lung disorder, causes PAH in young adults and mostly is diagnosed after death by autopsy. PoPH is defined as PAH due to primary chronic liver disease associated with intrapulmonary vascular dilatations and hypoxia. HIV associated PAH is a rare complication of HIV-infection, and it is seen especially in HIV-infected patients with intravenous drug abuse.


Chemical Analysis of Microplastics and Nanoplastics: Challenges, Advanced Methods, and Perspectives.
Microplastics and nanoplastics have become emerging particulate anthropogenic pollutants and rapidly turned into a field of growing scientific and public interest. These tiny plastic particles are found in the environment all around the globe as well as in drinking water and food, raising concerns about their impacts on the environment and human health. To adequately address these issues, reliable information on the ambient concentrations of microplastics and nanoplastics is needed. However, micro- and nanoplastic particles are extremely complex and diverse in terms of their size, shape, density, polymer type, surface properties, etc. While the particle concentrations in different media can vary by up to 10 orders of magnitude, analysis of such complex samples may resemble searching for a needle in a haystack. This highlights the critical importance of appropriate methods for the chemical identification, quantification, and characterization of microplastics and nanoplastics. The present article reviews advanced methods for the representative mass-based and particle-based analysis of microplastics, with a focus on the sensitivity and lower-size limit for detection. The advantages and limitations of the methods, and their complementarity for the comprehensive characterization of microplastics are discussed. A special attention is paid to the approaches for reliable analysis of nanoplastics. Finally, an outlook for establishing harmonized and standardized methods to analyze these challenging contaminants is presented, and perspectives within and beyond this research field are discussed.


Tumor cell survival and resistance to therapy.
The primary reason for the failure to cure patients with cancer remains the development of multiple mechanisms of resistance to cytotoxic agents. The two major effectors of tumor cell killing include genotoxic agents and cell-mediated immunity. Genotoxic agents function primarily by initiating pathways leading to apoptosis or programmed cell death, whereas immune-mediate cytotoxicity utilizes both programmed cell death-promoting as well as cytolytic processes. The mechanisms leading to treatment resistance initially involve alterations in the way tumor cells transport, metabolize, and provide substrates for cytotoxic agents. Beyond these specific mechanisms, tumor cells may also express alterations in the regulators and effectors of apoptotic death, thus creating a more generalized resistance pattern. Through a variety of other mechanisms, tumor cells may also decrease specific antigen expression or the ability to costimulate T lymphocytes. The result of antigen recognition in the absence of costimulation can lead to antigen-specific tolerance, which may also represent a major form of escape from immune-mediated killing. The elucidation of these mechanisms of resistance to therapy and tumor cell survival should form the basis for the development of more effective therapies.


Embodying pervasive discrimination: a decomposition of sexual orientation inequalities in health in a population-based cross-sectional study in Northern Sweden.
Studies from Sweden and abroad have established health inequalities between heterosexual and non-heterosexual people. Few studies have examined the underpinnings of such sexual orientation inequalities in health. To expand this literature, the present study aimed to employ decomposition analysis to explain health inequalities between people with heterosexual and non-heterosexual orientation in Sweden, a country with an international reputation for heeding the human rights of non-heterosexual people. Participants (N = 23,446) came from a population-based cross-sectional survey in the four northernmost counties in Sweden in 2014. Participants completed self-administered questionnaires, covering sexual orientation, mental and general physical health, social conditions and unmet health care needs, and sociodemographic data was retrieved from total population registers. Sexual orientation inequalities in health were decomposed by Blinder-Oaxaca decomposition analysis. Results showed noticeable mental and general health inequalities between heterosexual and non-heterosexual orientation groups. Health inequalities were partly explained (total explained fraction 64-74%) by inequalities in degrading treatment (24-26% of the explained fraction), but to a considerable degree also by material conditions (38-45%) and unmet care needs (25-43%). Psychosocial experiences may be insufficient to explain and understand health inequalities by sexual orientation in a reputedly 'gay-friendly' setting. Less overt forms of structural discrimination may need to be considered to capture the pervasive material discrimination that seems to underpin the embodiment of sexual minority inequalities. This ought to be taken into consideration in research, policy-making and monitoring aiming to work towards equity in health across sexual orientations.


Comparison of efficacy of pantoprazole alone versus pantoprazole plus mosapride in therapy of gastroesophageal reflux disease: a randomized trial.
The present study aimed to compare the efficacy for the therapy of GERD of pantoprazole alone with a combination of pantoprazole and mosapride. The study was a prospective, randomized trial involving 68 patients suffering heartburn and/or regurgitation at least twice a week for 6 weeks. Sixty-one patients consented to be randomized to receive either pantoprazole 40 mg b.i.d. (n = 33, group A) or pantoprazole 40 mg b.i.d. plus mosapride 5 mg t.d.s. (n = 28, group B) for 8 weeks. Twenty-four-hour esophageal pH-metry and endoscopy were conducted at recruitment and endoscopy was repeated at 8 weeks in all the patients studied. There were no differences in symptomatic responses to therapy between the groups (69.7% vs 89.2%; P = 0.11). The mean symptom score after 8 weeks was significantly lower in group B (3.78 +/- 3.62 vs 1.67 +/- 2.09; P = 0.009). Nonerosive esophagitis was present in 29 patients. In patients with nonerosive GERD there was no significant difference in symptomatic response to either regimen (17/20 in group A and 7/9 in group B responded; P = 0.63). In erosive esophagitis, symptomatic responses occurred more frequently in group B, 18/19 (94.7%), than in group A, 6/13 (46.2%; P = 0.003). However endoscopic healing of esophagitis occurred equally with either regimen (6/11, 54.5% in group A; 12/17, 70.5% in group B; P = 0.44). In nonerosive GERD, the addition of mosapride offers no benefit over pantoprazole alone. A combination of pantoprazole and mosapride is more effective than pantoprazole alone in providing symptomatic relief to patients with erosive GERD.