Qualitative sonographic assessment of transmural ileal inflammation in Crohn's disease: a comparison with MRI activity score.
Intestinal ultrasound (IUS) is an accurate tool for monitoring Crohn's disease. To date, there is no clinically used validated quantitative ultrasonographic score for assessing disease activity. For magnetic resonance enterography (MRE), the magnetic resonance index of activity (MaRIA) is most used. The goal of this study was to devise a new quantitative IUS score for assessing Crohn's disease inflammation, by using a partial MaRIA score as a reference. This was a retrospective cohort study. The study cohort included patients with Crohn's disease followed between January 2016 and December 2018. Inclusion criteria were age >18 and <3 months between MRE and IUS. Linear/logistic regression was performed for the correlation of ultrasonographic parameters with MaRIA score. Ultrasonograpic features included: bowel wall thickness, disrupted bowel wall stratification, mesenteric fat proliferation, presence of lymph nodes, hypervascularity present on color Doppler flow, and the presence of complications (strictures, inflammatory mass, and fistula). Forty-two patients were included. A stepwise multiple regression model was constructed to predict MaRIA score using ultrasound features. Two variables were found to be independently significant: terminal ileum (TI) thickness (r = 0.68, P = 0.001) and mesenteric fat proliferation (r = 0.45, P = 0.019). A model was constructed as follows: MaRIA = 7 + 2.5 * TI US thickness (mm) + 7 * US fat proliferation (0 = no, 1 = yes). This model has an R2 of 0.51 for explaining the variability in the results. IUS measurements are significantly correlated with MaRIA score in the terminal ileum and a simple computational model can be constructed.


The effects of non-weight bearing on skeletal muscle in older rats: an interrupted bout versus an uninterrupted bout.
Age-related changes in skeletal muscle, in combination with bed rest, may result in a poorer rehabilitation potential for an elderly patient. The purpose of this study was to determine the effects of non-weight bearing (hind limb unweighting [HU]) on the soleus and extensor digitorum longus (EDL) in older rats. Two non-weight bearing conditions were used: an uninterrupted bout of HU and an interrupted bout of HU. Twenty-one rats were randomly placed into 1 of 3 groups: control, interrupted HU (2 phases of 7 days of HU, separated by a 4-day weight-bearing phase) and an uninterrupted HU (18 uninterrupted days of HU). Following non-weight bearing, the soleus and EDL muscles were removed. Fiber type identification was performed by myofibrillar ATPase and cross-sectional area was determined. The findings suggest that any period of non-weight bearing leads to a decrease in muscle wet weight (19%-45%). Both type I and type II fibers of the soleus showed atrophy (decrease in cross-sectional area, 35%-44%) with an uninterrupted bout of non-weight bearing. Only the type II fibers of the soleus showed recovery with an interrupted bout of weight bearing. In the EDL, type II fibers were more affected by an uninterrupted bout of non-weight bearing (15% decrease in fiber size) compared to the type I fibers. EDL type II fibers showed more atrophy with interrupted bouts of non-weight bearing than with a single bout (a 40% compared to a 15% decrease). This study shows that initial weight bearing after an episode of non-weight bearing may be damaging to type II fibers of the EDL.


Long-Lasting Analgesia With Transdermal Fentanyl: A New Approach in Rat Neonatal Research.
Background: With advances in neonatal care, management of prolonged pain in newborns is a daily concern. In addition to ethical considerations, pain in early life would have long-term effects and consequences. However, its treatment remains inadequate. It was therefore important to develop an experimental model of long-lasting analgesia for neonatal research. Materials and Methods: Experiments were performed in six groups of rats with transdermal fentanyl 0, 3, 12, 50, 100, or 200 μg/kg/h from second postnatal day (P2) until weaning. Assessment of analgesia was carried out at P21, with behavioral scores (ranging from 0 to 3) using a 4% formalin test. Plasma levels of fentanyl were determined by UPLC/TQD at P22. Growth rate was investigated. Results: Fentanyl 100 and 200 μg/kg/h reduced scores of formalin-evoked behavioral pain. They increased time spent in pain score 0 (8 min 55 s and 6 min 34 s versus 23 s in controls) as in low pain scores 1 and 2, and decreased time in the most severe pain score 3 (19 min 56 s and 17 min 39 s versus 44 min 15 s). Fentanylemia increased in a dose-dependent manner from 50 μg/kg/h (2.36 ± 0.64 ng/ml) to 200 μg/kg/h (8.66 ± 1.80 ng/ml). Concerning growth, no difference was observed except weaker growth from P17 to P22 with 200 μg/kg/h. Clinically, we noticed no visible side effect from 3 to 100 μg/kg/h. Concomitantly, 200 μg/kg/h was responsible for ophthalmological side effects with appearance of corneal bilateral clouding in 90% pups. No difference was observed between male and female rats. Conclusion: Altogether, results indicate that transdermal fentanyl 100 μg/kg/h is an efficient therapeutic for long-lasting analgesia in lactating pups. This new model provides a useful tool for protection and welfare, and future opportunity for studying long-term health consequences of sustainable neonatal analgesia.


Elbow fat pads with new signs and extended differential diagnosis.
Although fat pad signs are classically associated with fracture, there are many nontraumatic disease processes which lead to positive fat pad signs. Any intraarticular fluid or tissue accumulation may result in an abnormal posterior fat pad. A "paradoxical" positive posterior fat pad sign may occur in some instances of extraarticular disease. An extended differential diagnosis is presented.


Primary care utilization and clinical quality performance: a comparison between health centres in Medicaid expansion states and non-expansion states.
The United States Government's Medicaid expansion policy has important implications for health centres, since a large proportion of health centre patients are Medicaid enrollees. The objective of this study was to compare primary care utilization and clinical quality performance between health centres in Medicaid expansion states and those in Medicaid non-expansion states. We conducted a cross-sectional study. Multiple regressions, using a standard linear model, were performed to examine the relationship between Medicaid expansion status and performance measures, accounting for covariates. Our results showed that in unadjusted analyses, health centres in Medicaid expansion states reported larger number of patients served, larger number of medical visits, a higher percentage of Medicaid patients, and better performance in seven of 16 clinical quality measures than those in Medicaid non-expansion states. After controlling for relevant health centre-level covariates, the differences in mean patients served, mean medical visits, percentage of Medicaid patients, and five clinical quality measures still existed. These findings reveal significant associations between Medicaid expansion and primary care utilization and the quality of care. Medicaid expansion has demonstrated its potential role in promoting primary care for vulnerable populations served by health centres.


Structure/function analysis of the interaction of adenomatous polyposis coli with DNA polymerase beta and its implications for base excision repair.
Mutations in the adenomatous polyposis coli (APC) gene are associated with an early onset of colorectal carcinogenesis. Previously, we described a novel role for the APC polypeptide in base excision repair (BER). The single-nucleotide (SN) and long-patch (LP) BER pathways act to repair the abasic sites in DNA that are induced by stressors, such as spontaneous oxidation/reduction, alkylation, and hyperthermia. We have shown that APC interacts with DNA polymerase beta (Pol-beta) and flap endonuclease 1 (Fen-1) and blocks Pol-beta-directed strand-displacement synthesis. In this study, we have mapped the APC interaction site in Pol-beta and have found that Thr79, Lys81, and Arg83 of Pol-beta were critical for its interaction with APC. The Pol-beta protein (T79A/K81A/R83A) blocked strand-displacement DNA synthesis in which tetrahydrofuran was used as DNA substrate. We further showed that the APC-mediated blockage of LP-BER was due to inhibition of Fen-1 activity. Analysis of the APC-mediated blockage of SN-BER indicated that the interaction of APC with Pol-beta blocked SN-BER activity by inhibiting Pol-beta-directed deoxyribose phosphate lyase activity. Collectively, our findings indicate that APC blocked both Pol-beta-directed SN- and LP-BER pathways and increased sensitivity of cells to alkylation induced DNA damage.


Foliar spray of silica improved water stress tolerance in rice (Oryza sativa L.) cultivars.
Rice (Oryza sativa L.) is a major cereal crop and a staple food across the world, mainly in developing countries. Drought is one of the most important limiting factors for rice production, which negatively affects food security worldwide. Silica enhances antioxidant activity and reduces oxidative damage in plants. The current study evaluated the efficiency of foliar spray of silica in alleviating water stress of three rice cultivars (Giza178, Sakha102, and Sakha107). The seedlings of the three cultivars were foliar sprayed with 200 or 400 mg l-1 silica under well-watered [80% water holding capacity (WHC)] and drought-stressed (40% WHC)] conditions for two summer seasons of 2019 and 2020. The obtained results demonstrated that drought stress caused significant decreases in growth, yield, and physiological parameters but increases in biochemical parameters (except proline) of leaves in all rice cultivars compared to well-irrigated plants (control). The roots of drought-stressed seedlings exhibited smaller diameters, fewer numbers, and narrower areas of xylem vessels compared to those well-watered. Regardless of its concentration, the application of silica was found to increase the contents of photosynthetic pigments and proline. Water relation also increased in seedlings of the three tested rice cultivars that were treated with silica in comparison to their corresponding control cultivars when no silica was sprayed. Foliar application of 400 mg l-1 silica improved the physiological and biochemical parameters and plant growth. Overall, foliar application of silica proved to be beneficial for mitigating drought stress in the tested rice cultivars, among which Giza178 was the most drought-tolerant cultivar. The integration of silica in breeding programs is recommended to improve the quality of yield and to provide drought-tolerant rice cultivars under drought-stress conditions.


Alcohol Use, HIV Stigma and Quality of Life Among Alcohol Consuming Men Living with HIV in India: A Mediation Analysis.
This study examined the hypothesis that HIV-related stigma mediates the effect of alcohol use on health-related quality of life (HRQoL) among alcohol consuming Indian men living with HIV (PLWH). The study used baseline data from a randomized controlled clinical trial entitled 'Alcohol and ART adherence: Assessment, Intervention, and Modeling in India. Participants completed surveys assessing demographic characteristics, alcohol use, HIV-related stigma, HRQoL. Mediation analysis was conducted to establish the mediation effect of HIV-related stigma on the relationship between alcohol use and HRQoL. The final mediation model showed that the effect of alcohol use on HRQoL were partially mediated by overall HIV-related stigma. Specially, 27.1% of the effects of alcohol use on HRQoL was mediated through overall HIV stigma. In the HIV stigma subdomain analyses, negative self-image mediated 14% and concerns with public attitudes (anticipated stigma) mediated 17.3% of the effect of alcohol use on HRQoL respectively. The findings suggest that efforts to reduce the negative impact of alcohol use on HRQoL and improve HRQoL among PLWH should include interventions addressing both alcohol use and specific forms of HIV-related stigma.


Mars promotes dTACC dephosphorylation on mitotic spindles to ensure spindle stability.
Microtubule-associated proteins (MAPs) ensure the fidelity of chromosome segregation by controlling microtubule (MT) dynamics and mitotic spindle stability. However, many aspects of MAP function and regulation are poorly understood in a developmental context. We show that mars, which encodes a Drosophila melanogaster member of the hepatoma up-regulated protein family of MAPs, is essential for MT stabilization during early embryogenesis. As well as associating with spindle MTs in vivo, Mars binds directly to protein phosphatase 1 (PP1) and coimmunoprecipitates from embryo extracts with minispindles and Drosophila transforming acidic coiled-coil (dTACC), two MAPs that function as spindle assembly factors. Disruption of binding to PP1 or loss of mars function results in elevated levels of phosphorylated dTACC on spindles. A nonphosphorylatable form of dTACC is capable of rescuing the lethality of mars mutants. We propose that Mars mediates spatially controlled dephosphorylation of dTACC, which is critical for spindle stabilization.


How can a child be a mother? Discourse on teenage pregnancy in a Brazilian favela.
Contemporary research reveals the body as a privileged place for social memory and resistance, especially among those people who are politically and economically marginalized. But what might the body signify within the context of teenage pregnancy in conditions of chronic poverty? To explore these issues, semi-structured interviews were conducted with 21 boys and 17 girls living in a favela in São Paulo, Brazil. In their responses, young people drew a clear distinction between sex and parenthood. If sex sometimes holds negative connotations, maternity and the physical appearance of pregnancy increases social status. Young people's representations of teenage pregnancy do not portray it as a social or health problem. Instead, they understand it as a consequence of the desire to be visible and active in social life. Findings highlight the importance of investigating the relationship between young people's sexuality and the social imaginary, particularly in conditions of social inequality and suffering.


Role of CXCR2 in cigarette smoke-induced lung inflammation.
It has been hypothesized that the destruction of lung tissue observed in smokers with chronic obstructive pulmonary disease and emphysema is mediated by neutrophils recruited to the lungs by smoke exposure. This study investigated the role of the chemokine receptor CXCR2 in mediating neutrophilic inflammation in the lungs of mice acutely exposed to cigarette smoke. Exposure to dilute mainstream cigarette smoke for 1 h, twice per day for 3 days, induced acute inflammation in the lungs of C57BL/6 mice, with increased neutrophils and the neutrophil chemotactic CXC chemokines macrophage inflammatory protein (MIP)-2 and KC. Treatment with SCH-N, an orally active small molecule inhibitor of CXCR2, reduced the influx of neutrophils into the bronchoalveolar lavage (BAL) fluid. Histological changes were seen, with drug treatment reducing perivascular inflammation and the number of tissue neutrophils. beta-Glucuronidase activity was reduced in the BAL fluid of mice treated with SCH-N, indicating that the reduction in neutrophils was associated with a reduction in tissue damaging enzymes. Interestingly, whereas MIP-2 and KC were significantly elevated in the BAL fluid of smoke exposed mice, they were further elevated in mice exposed to smoke and treated with drug. The increase in MIP-2 and KC with drug treatment may be due to the decrease in lung neutrophils that either are not present to bind these chemokines or fail to provide a feedback signal to other cells producing these chemokines. Overall, these results demonstrate that inhibiting CXCR2 reduces neutrophilic inflammation and associated lung tissue damage due to acute cigarette smoke exposure.


Induction of apoptosis in frog virus 3-infected cells.
The ability of frog virus 3 (FV3), the type species of the family Iridoviridae, to induce apoptosis was examined by monitoring DNA cleavage, chromatin condensation, and cell-surface expression of phosphotidylserine (PS) in fathead minnow (FHM) and baby hamster kidney (BHK) cells. In productively infected FHM cells, DNA fragmentation was first noted at 6-7 h postinfection and was clearly seen by 17 h postinfection, while chromatin condensation was detected at 8.5 h postinfection. As with some other viruses, FV3-induced apoptosis did not require de novo viral gene expression as both heat-inactivated and UV-inactivated virus readily triggered DNA fragmentation in FHM cells. Moreover, FV3-induced apoptosis was blocked in FHM cells by the pan-caspase inhibitor Z-VAD-FMK, suggesting that virus infection triggers programmed cell death through activation of the caspase cascade. FV3 infection also triggered apoptosis in BHK cells as monitored by TUNEL and annexin V binding assays. To determine whether FV3, similar to other large DNA viruses, encoded proteins that block or delay apoptosis, mock- and FV3-infected FHM cells were osmotically shocked and assayed for DNA fragmentation 3 hours later. DNA fragmentation was clearly seen whether or not shocked cells were previously infected with FV3, indicating that infection with FV3 did not block apoptosis induced by osmotic shock in FHM cells. The above results demonstrate that iridoviruses triggered apoptosis and that the induction of programmed cell death did not require viral gene expression. However, it remains to be determined if virion attachment to target cells is sufficient to induce cell death, or if apoptosis is triggered directly or indirectly by one or more virion-associated proteins.


Current status and future of implantable insulin pumps for the treatment of diabetes.
The data from the Diabetes Control and Complications Trial show that control of blood glucose with intensive insulin therapy significantly delays complications of diabetes when compared with conventional therapy consisting of one or two insulin injections per day. However, the subcutaneous intensive insulin therapy, including insulin infusion by external pumps, required to achieve the glycemic goals defined by the Diabetes Control and Complications Trial, led to an increased frequency of severe hypoglycemia. Improvements in parenteral insulin therapy are possible by either modifying subcutaneous insulin kinetics (insulin analogs) or developing better routes of administration. Intraperitoneal insulin infusion offers a more physiologic route of insulin delivery. The ultimate goal for the treatment of diabetes remains the development of a fully automated glucose-controlled device.


Expression and clinical significance of ATM and PUMA gene in patients with colorectal cancer.
The expression of ataxia-telangiectasia mutated (ATM) and p53 upregulated modulator of apoptosis (PUMA) genes in patients with colorectal cancer were investigated, to explore the correlation between the expression of ATM and PUMA and tumor development, to evaluate the clinical significance of ATM and PUMA in the treatment of colorectal cancer. Quantitative real-time PCR was used to detect the expression of ATM and PUMA in tumor tissue and adjacent healthy tissue of 67 patients with colorectal cancer and in normal colorectal tissue of 33 patients with colorectal polyps at mRNA level. The expression level of ATM mRNA in colorectal cancer tissues was significantly higher than that in normal mucosa tissues and adjacent non-cancerous tissue (P≤0.05), while no significant differences in expression level of ATM mRNA were found between normal mucosa tissues and adjacent noncancerous tissue (P=0.07). There was a negative correlation between the expression of ATM mRNA and the degree of differentiation of colorectal cancer (r= -0.312, P=0.013), while expression level of ATM mRNA was not significantly correlated with the age, sex, tumor invasion, lymph node metastasis or clinical stage (P>0.05). Expression levels of PUMA mRNA in colorectal cancer tissues, adjacent noncancerous tissue and normal tissues were 0.68±0.07, 0.88±0.04 and 1.76±0.06, respectively. Expression level of PUMA mRNA in colorectal cancer tissues and adjacent noncancerous tissue was significantly lower than that in normal colorectal tissues (P<0.05). The results showed that ATM mRNA is expressed abnormally in colorectal cancer tissues. Expression of PUMA gene in colorectal carcinoma is downregulated, and is negatively correlated with the occurrence of cancer.


Cogrinding Wood Fibers and Tannins: Surfactant Effects on the Interactions and Properties of Functional Films for Sustainable Packaging Materials.
We report on the combination of cellulose nanofibrils (CNFs) and condensed tannins from Acacia mearnsii for the development of hybrid, functional films. The tannins are fractionated and concentrated in polyphenolics that are used for functional components in the hybrid materials. Cogrinding of wood fibers with the tannins in aqueous media allows simultaneous fiber deconstruction and in situ binding of tannins on the freshly exposed cellulosic surfaces. Hence, a tightly bound bicomponent system is produced, which is otherwise not possible if typical adsorption protocols are followed, mainly due to the extensive hydration typical of CNFs. A nonionic surfactant is used to tailor the cellulose-tannin interactions. The proposed strategy not only enables the incorporation of tannins with CNFs but also endows a high and prolonged antioxidant effect of films formed by filtration. Compared to tannin-free films, those carrying tannins are considerably more hydrophobic. In addition, they show selective absorption of ultraviolet light while maintaining optical transparency in the visible range. The proposed simple protocol for incorporating tannins and surfactants with CNFs is suitable to produce functional materials. This is possible by understanding associated interfacial phenomena in the context of sustainable materials within the concept of the circular bioeconomy.


Effect of Surface Chemistry on Confined Phase Behavior in Nanoporous Media: An Experimental and Molecular Modeling Study.
It is well accepted that nanopore size is a controlling parameter in determining the phase behavior of confined adsorbate molecules. Despite this knowledge, the quantitative effect of surface chemistry on the confined phase behavior is a factor that remains obfuscated. Obtaining a complete understanding of the variables controlling confined phase behavior is a critical step in developing more complete equations of state for predictive modeling. To this end, a combined experimental and molecular modeling study was conducted to investigate the effects of surface chemistry and wetting on the confined phase behavior of propane and n-butane in modified and unmodified silica MCM-41. Isotherms were measured in four types of silica MCM-41 modified with varying sizes of alkyl groups to determine the effects of increasing surface modification. Results showed that increased pore surface coverage of carbon resulted in a notable change in the capillary condensation pressures, adsorption enthalpy, and confined critical temperature of the adsorbate. Correlations between the surface coverage of carbon and the confined critical temperature were presented and supported by thermodynamic arguments. The primary conclusions were partially supported by hybrid molecular dynamics-Monte Carlo simulations of propane adsorption in models of the four types of experimental adsorbents. Several differences were noted and explained between the experimental and modeling results. Energetic heterogeneity on the surface of the modified MCM-41 adsorbents as well as differences in adsorbate entropy induced by surface features and chemistry were suggested as primary driving factors for the observed trends. The results of this work have direct implications for improving understanding of confined phase behavior in materials of varying surface chemistries.


[Aneurysms as a rare cause of chronic subdural hematomas].
Chronic subdural haematomas are nowadays usually diagnosed via computed tomography. Followups are also by this method. It is therefore inevitable that aneurysms or other vascular malformations are overlooked as rare but important causes of such haematomas. If anamnesis, findings and course are atypical, it is recommended to attempt additional angiographic clarification at least in such cases.


Supracondylar corrective osteotomy for cubitus varus--the internal rotation component and its importance. An unique bone experiment.
In 20 patients with cubitus varus, a clinical test suggested by Yamamoto et al (1985) was carried out to measure the internal rotation. Average internal rotation was found to be 37.5 +/- 9.390. A correction for internal rotation was carried out for all the patients having angle more than 20 degrees. Following osteotomy, post-operative Yamamoto's angle was measured and was found to be 8.85 +/- 6.5. An experiment was carried out on postmortem human humerus with cubitus varus. The internal rotation was measured with Kirschner wires and was found to be 30 degrees. Osteotomy was carried out to eliminate varus and correct internal rotation. Radiographs taken before and after the osteotomy confirmed the correction. We conclude that this derotation has to be corrected and Yamamoto's test should be used to assess the correction.


Autoantibodies to osteopontin in patients with osteoarthritis and rheumatoid arthritis.
Osteopontin (OPN), secreted mainly from chondrocytes, is suggested to be involved in the ossification and remodeling of bone and also in regulation of cytokine profiles. We investigated whether patients with osteoarthritis (OA) and rheumatoid arthritis (RA) display autoimmunity against OPN. Recombinant human OPN (rhOPN) was prepared as a fusion protein with beta-galactosidase using E. coli. Serum samples from patients with OA or RA and from age matched healthy donors were tested for autoantibodies to rhOPN using ELISA and Western blotting. Reactivity of the same samples to purified native human OPN (nhOPN) was investigated by ELISA separately, to evaluate conformational epitopes. By ELISA, autoantibodies to rhOPN were found in one (0.95%) of 105 patients with OA and 2 (2.3%) of 88 patients with RA. These autoantibodies to rhOPN were confirmed by Western blotting. In contrast, 11 (9.5%) of 105 OA serum and 13 (15%) of 88 RA serum samples reacted to nhOPN. The anti-OPN positive RA patients showed high serum levels of rheumatoid factor and C-reactive protein and accelerated erythrocyte sedimentation rate compared to the anti-OPN negative group, although the differences did not achieve statistical significance. Our data showed that OPN is one of the autoantigens in OA and RA. Preferential recognition of nhOPN to rhOPN indicates that major epitope(s) of OPN would be conformational. Clinically, existence of the anti-OPN antibodies may be linked to disease severity in RA.


Limb anomalies in patients with CHARGE syndrome: an expansion of the phenotype.
CHARGE syndrome is characterized by a wide clinical variability. During the past years the phenotypic spectrum was markedly expanded. Limb anomalies were initially not recognized as part of the phenotype but more recently mild limb anomalies were described in approximately 30% of the patients. We report on three patients with several major features of CHARGE syndrome who, in addition, presented severe limb anomalies including monodactyly, tibia aplasia, and bifid femora. Three different heterozygous truncating mutations in the CHD7 gene were detected. It has been hypothesized before that the CHARGE syndrome is caused by a disruption of mesenchymal-epithelial interaction. Given the expression of the CHD7 gene in the developing limb bud, it was anticipated that limb defects would belong to the spectrum of manifestations of CHARGE syndrome. The present observations provide further support to this hypothesis.


Beneficial Effects of a Mixture of Algae and Extra Virgin Olive Oils on the Age-Induced Alterations of Rodent Skeletal Muscle: Role of HDAC-4.
Aging is associated with a progressive decline in skeletal muscle mass, strength and function (sarcopenia). We have investigated whether a mixture of algae oil (25%) and extra virgin olive oil (75%) could exert beneficial effects on sarcopenia. Young (3 months) and old (24 months) male Wistar rats were treated with vehicle or with the oil mixture (OM) (2.5 mL/kg) for 21 days. Aging decreased gastrocnemius weight, total protein, and myosin heavy chain mRNA. Treatment with the OM prevented these effects. Concomitantly, OM administration decreased the inflammatory state in muscle; it prevented the increase of pro-inflammatory interleukin-6 (IL-6) and the decrease in anti-inflammatory interleukin-10 (IL-10) in aged rats. The OM was not able to prevent aging-induced alterations in either the insulin-like growth factor I/protein kinase B (IGF-I/Akt) pathway or in the increased expression of atrogenes in the gastrocnemius. However, the OM prevented decreased autophagy activity (ratio protein 1A/1B-light chain 3 (LC3b) II/I) induced by aging and increased expression of factors related with muscle senescence such as histone deacetylase 4 (HDAC-4), myogenin, and IGF-I binding protein 5 (IGFBP-5). These data suggest that the beneficial effects of the OM on muscle can be secondary to its anti-inflammatory effect and to the normalization of HDAC-4 and myogenin levels, making this treatment an alternative therapeutic tool for sarcopenia.


Gender differences in the frequency and treatment of behavior problems in Parkinson's disease.
To determine gender differences in the prevalence, survival rates, and management of noncognitive behavioral problems of patients with Parkinson's disease (PD) in nursing homes (NH). We performed an observational study on 24,402 residents with PD using the Systematic Assessment and Geriatric drug use via Epidemiology (SAGE) database collected from the Minimum Data Set on a cross-section of over 400,000 NH residents in five US states. Gender differences in behavior were used to predict differences in pharmacologic and nonpharmacologic therapies using logistic regression. Similar analyses were done to evaluate gender differences in 1-year survival rates among patients with PD with and without behavioral problems. 36% of men and 33% of women exhibited behavioral problems. Wandering, verbal and physical abusiveness, and inappropriate behavior tended to be more common in men, especially among PD residents with severe cognitive impairment. Hallucinations and delusions were equally prevalent between genders and depressive symptoms were more common in women. Regardless of behavioral manifestation, men were more likely to receive antipsychotic drugs, whereas women were more likely to receive antidepressants. This gender difference in treatment was also widest among the severely demented group. Although women lived longer, no difference in survival curves were noted between PD residents with and without behavioral problems. Gender appears to play an important role in determining the frequency and treatment of behavioral problems of NH residents with PD.


Yoga into Cancer Care: A Review of the Evidence-based Research.
To cope with cancer and its treatment-related side effects and toxicities, people are increasingly using complementary and alternative medicine (CAM). Consequently, integrative oncology, which combines conventional therapies and evidence-based CAM practices, is an emerging discipline in cancer care. The use of yoga as a CAM is proving to be beneficial and increasingly gaining popularity. An electronic database search (PubMed), through December 15, 2016, revealed 138 relevant clinical trials (single-armed, nonrandomized, and randomized controlled trials) on the use of yoga in cancer patients. A total of 10,660 cancer patients from 20 countries were recruited in these studies. Regardless of some methodological deficiencies, most of the studies reported that yoga improved the physical and psychological symptoms, quality of life, and markers of immunity of the patients, providing a strong support for yoga's integration into conventional cancer care. This review article presents the published clinical research on the prevalence of yoga's use in cancer patients so that oncologists, researchers, and the patients are aware of the evidence supporting the use of this relatively safe modality in cancer care.


Orthopaedic complications of Lyme disease in children.
Lyme disease is transmitted by the tick Ixodes dammini ("deer tick") or a related ixodid tick. Early diagnosis of children with Lyme disease is difficult because the bite of the ixodid tick often goes unnoticed. Furthermore, erythema chronicum migrans, the characteristic rash of the disease, occurs in less than 50% of cases. However, an awareness of orthopaedic complications of Lyme disease may facilitate an early diagnosis of this disease. Orthopaedic complications of Lyme disease include those which are oligoarticular in nature. Brief intermittent attacks of swelling and pain in one or more joints--primarily large ones--is the pattern of disease most frequently presented. The knee is the joint most commonly affected. In most cases, pain is not severe enough to debilitate the patient or prevent weight-bearing activity. An elevated sedimentation rate is the only consistently abnormal routine laboratory finding in Lyme disease. The only radiographic abnormalities noted in children are effusion and osteopenia. However, the radiograph of a patient known to have Lyme disease may not show any abnormalities at all. Lyme disease shares symptoms in common with septic arthritis and juvenile rheumatoid arthritis. Whenever a distinction between Lyme arthritis and septic arthritis is difficult to make, treatment should be directed at septic arthritis while serological tests for Lyme disease are pending. The physician should consider Lyme disease to be a possible diagnosis of any patient with arthritis and a history of rash or fever, idiopathic neurological disease, or a cardiac conduction defect--especially if there is a history of possible exposure to the carrier tick.(ABSTRACT TRUNCATED AT 250 WORDS)


Factors influencing mothers' decisions to consult a general practitioner about their children's illnesses.
In the management of childhood illness only a small proportion of symptoms result in a medical consultation. This pilot study set out to assess the influence of sociodemographic factors, social network, reason of choice of doctor and contact with allied health professionals on mothers' decisions to consult a general practitioner about their children's illnesses. In one suburb of Melbourne, Australia all mothers with children aged 11 to 26 months were identified from the maternal and child health centre register. Mothers were invited for interview and if they attended were asked to keep a health diary for their child for four weeks. Logistic regression was used to test a multivariate model of factors predicting consultation with the general practitioner. A total of 150 mothers were identified. Interviews were carried out with 81% of target mothers and diary data collected for 72% of target children. Over the four-week diary period, consultation rates with the general practitioner were significantly higher if symptoms were recorded on 15 days or more, or the general practitioner had been recommended by a friend or was the mother's own doctor before the child's birth. Contact with a maternal and child health nurse was also a significant predictor of medical contact. Contact with friends and relatives, whether or not the study child was the first child in the family, mother's education, husband's occupational status or contact with a chemist were not significantly related to medical consultation rates. Choice of doctor (current doctor same as doctor before birth of child, or doctor recommended by a friend) resulted in significantly more consultations as did contact with a maternal and child health nurse. These factors would seem to require further study and inclusion in future models of consulting behaviour.


MiR-204 promotes fracture healing via enhancing cell viability of osteoblasts.
To investigate the effects and related mechanisms of miR-204 on fracture healing. Mouse osteoblastic cell line MC3T3-E1 was used in our experiment. Three groups were established to investigate the potential function between miR-204 and osteoblastic cells: miR-NC group (negative control), miR-204 mimics group (MC3T3-E1 cells transfected with miR-204 mimics) and miR-204 mimics + inhibitor group (MC3T3-E1 cells transfected with miR-204 mimics and inhibitor). After incubation, cell viability, activity of caspase-3, and migration ability of MC3T3-E1 cells, were measured. Further, the expression levels of Runt-related transcription factor 2 (RUNX2) and Osterix (OSX) were detected and analyzed. Compared with miR-NC group, the cell viability and migration ability of MC3T3-E1 cells were enhanced while the activity of caspase-3 was respectively mitigated. Besides, the expression level of RUNX2 and OSX was increased by treatment of miR-204 mimics. However, these variations of the indicators were reversed by the intervention using miR-204 inhibitor. We revealed the promotion effect of miR-204 on fracture healing, indicating that miR-204 could be a potential therapeutic target for the treatment of a fracture.


Role of structure and glycosylation of adsorbed protein films in biolubrication.
Water forms the basis of lubrication in the human body, but is unable to provide sufficient lubrication without additives. The importance of biolubrication becomes evident upon aging and disease, particularly under conditions that affect secretion or composition of body fluids. Insufficient biolubrication, may impede proper speech, mastication and swallowing, underlie excessive friction and wear of articulating cartilage surfaces in hips and knees, cause vaginal dryness, and result in dry, irritated eyes. Currently, our understanding of biolubrication is insufficient to design effective therapeutics to restore biolubrication. Aim of this study was to establish the role of structure and glycosylation of adsorbed protein films in biolubrication, taking the oral cavity as a model and making use of its dynamics with daily perturbations due to different glandular secretions, speech, drinking and eating, and tooth brushing. Using different surface analytical techniques (a quartz crystal microbalance with dissipation monitoring, colloidal probe atomic force microscopy, contact angle measurements and X-ray photo-electron spectroscopy), we demonstrated that adsorbed salivary conditioning films in vitro are more lubricious when their hydrophilicity and degree of glycosylation increase, meanwhile decreasing their structural softness. High-molecular-weight, glycosylated proteins adsorbing in loops and trains, are described as necessary scaffolds impeding removal of water during loading of articulating surfaces. Comparing in vitro and in vivo water contact angles measured intra-orally, these findings were extrapolated to the in vivo situation. Accordingly, lubricating properties of teeth, as perceived in 20 volunteers comprising of equal numbers of male and female subjects, could be related with structural softness and glycosylation of adsorbed protein films on tooth surfaces. Summarizing, biolubrication is due to a combination of structure and glycosylation of adsorbed protein films, providing an important clue to design effective therapeutics to restore biolubrication in patients with insufficient biolubrication.


Polysulfone and polyacrylate-based zwitterionic coatings for the prevention and easy removal of marine biofouling.
A series of polysulfone and polyacrylate-based zwitterionic coatings were prepared on epoxy-primed aluminum substrata and characterized for their antifouling (AF) and fouling-release (FR) properties towards marine bacteria, microalgae and barnacles. The zwitterionic polymer coatings provided minimal resistance against bacterial biofilm retention and microalgal cell attachment, but facilitated good removal of attached microbial biomass by exposure to water-jet apparatus generated hydrodynamic shearing forces. Increasing the ion content of the coatings improved the AF properties, but required a stronger adhesive bond to the epoxy-primed aluminum substratum to prevent coating swelling and dissolution. Grafted poly(sulfobetaine) (gpSBMA), the most promising zwitterionic coating identified from microfouling evaluations, enabled the removal of four out of five barnacles reattached to its surface without incurring damage to their baseplates. This significant result indicated that gpSBMA relied predominately on its surface chemistry for its FR properties since it was very thin (~1-2 µm) relative to commercial coating standards (>200 µm).


Disruption of insulin signalling affects the neuroendocrine stress reaction in Drosophila females.
Juvenile hormone (JH) and dopamine are involved in the stress response in insects. The insulin/insulin-like growth factor signalling pathway has also recently been found to be involved in the regulation of various processes, including stress tolerance. However, the relationships between the JH, dopamine and insulin signalling pathways remain unclear. Here, we study the role of insulin signalling in the regulation of JH and dopamine metabolism under normal and heat stress conditions in Drosophila melanogaster females. We show that suppression of the insulin-like receptor (InR) in the corpus allatum, a specialised endocrine gland that synthesises JH, causes an increase in dopamine level and JH-hydrolysing activity and alters the activities of enzymes that produce as well as those that degrade dopamine [alkaline phosphatase (ALP), tyrosine hydroxylase (TH) and dopamine-dependent arylalkylamine N-acetyltransferase (DAT)]. We also found that InR suppression in the corpus allatum modulates dopamine, ALP, TH and JH-hydrolysing activity in response to heat stress and that it decreases the fecundity of the flies. JH application restores dopamine metabolism and fecundity in females with decreased InR expression in the corpus allatum. Our data provide evidence that the insulin/insulin-like growth factor signalling pathway regulates dopamine metabolism in females of D. melanogaster via the system of JH metabolism and that it affects the development of the neuroendocrine stress reaction and interacts with JH in the control of reproduction in this species.


Impact of Mental Health Screening on Promoting Immediate Online Help-Seeking: Randomized Trial Comparing Normative Versus Humor-Driven Feedback.
Given the widespread availability of mental health screening apps, providing personalized feedback may encourage people at high risk to seek help to manage their symptoms. While apps typically provide personal score feedback only, feedback types that are user-friendly and increase personal relevance may encourage further help-seeking. The aim of this study was to compare the effects of providing normative and humor-driven feedback on immediate online help-seeking, defined as clicking on a link to an external resource, and to explore demographic predictors that encourage help-seeking. An online sample of 549 adults were recruited using social media advertisements. Participants downloaded a smartphone app known as "Mindgauge" which allowed them to screen their mental wellbeing by completing standardized measures on Symptoms (Kessler 6-item Scale), Wellbeing (World Health Organization [Five] Wellbeing Index), and Resilience (Brief Resilience Scale). Participants were randomized to receive normative feedback that compared their scores to a reference group or humor-driven feedback that presented their scores in a relaxed manner. Those who scored in the moderate or poor ranges in any measure were encouraged to seek help by clicking on a link to an external online resource. A total of 318 participants scored poorly on one or more measures and were provided with an external link after being randomized to receive normative or humor-driven feedback. There was no significant difference of feedback type on clicking on the external link across all measures. A larger proportion of participants from the Wellbeing measure (170/274, 62.0%) clicked on the links than the Resilience (47/179, 26.3%) or Symptoms (26/75, 34.7%) measures (χ2=60.35, P<.001). There were no significant demographic factors associated with help-seeking for the Resilience or Wellbeing measures. Participants with a previous episode of poor mental health were less likely than those without such history to click on the external link in the Symptoms measure (P=.003, odds ratio [OR] 0.83, 95% CI 0.02-0.44), and younger adults were less likely to click on the link compared to older adults across all measures (P=.005, OR 0.44, 95% CI 0.25-0.78). This pilot study found that there was no difference between normative and humor-driven feedback on promoting immediate clicks to an external resource, suggesting no impact on online help-seeking. Limitations included: lack of personal score control group, limited measures of predictors and potential confounders, and the fact that other forms of professional help-seeking were not assessed. Further investigation into other predictors and factors that impact on help-seeking is needed. Australian New Zealand Clinical Trials Registry ACTRN12616000707460; https://www.anzctr.org.au/ Trial/Registration/TrialReview.aspx?id=370187 (Archived by WebCite at http://www.webcitation.org/6y8m8sVxr).


Mucinous low-grade adenocarcinoma arising in an intracranial enterogenous cyst: case report.
Enterogenous cysts (ECs) of the central nervous system are developmental malformations that occur in the spinal canal, posterior fossa, or cerebral hemispheres. They are usually benign lesions, and malignant transformation is rare. To date, only three cases of malignant transformation have been reported in the literature. We present a case of a cerebellopontine EC showing foci of epithelial dysplasia and malignant transformation into a low-grade papillary mucinous adenocarcinoma. A 25 year-old man with a 6-year history of hypoacusia presented to our department with facial nerve deficit, visual disturbances, and gait instability. A magnetic resonance imaging scan demonstrated a multiloculated cerebellopontine angle cyst with supratentorial hydrocephalus. A retrosigmoidal approach was used to achieve cyst removal. This was followed several months later by ventriculoperitoneal shunt placement. The cyst was adherent to the brainstem, cranial nerves, and vessels, and it resembled a thin encapsulated structure filled with mucinous-like substance. No solid component was identified. Histopathological examination revealed an EC with foci of malignant transformation in a mucinous papillary adenocarcinoma. Magnetic resonance imaging was performed 5 months postoperatively due to progressive clinical worsening; this scan revealed lesion recurrence with severe brainstem compression. Emergency surgery was performed, and a large decompression was achieved. Subsequent follow-up computed tomographic scans showed progression of the residual tumor. The patient's neurological condition rapidly worsened, ultimately resulting in death. The present report suggests that a careful histological examination of all ECs after surgery should be made to exclude dysplastic foci or carcinomatous transformation. Although the clinical behavior of ECs with malignant transformation is unpredictable, surgery remains the treatment of choice. The use of possible adjuvant chemo- or radiotherapy has not been established.


Curcumin protects DNA damage in a chronically arsenic-exposed population of West Bengal.
Groundwater arsenic contamination has been a health hazard for West Bengal, India. Oxidative stress to DNA is recognized as an underlying mechanism of arsenic carcinogenicity. A phytochemical, curcumin, from turmeric appears to be potent antioxidant and antimutagenic agent. DNA damage prevention with curcumin could be an effective strategy to combat arsenic toxicity. This field trial in Chakdah block of West Bengal evaluated the role of curcumin against the genotoxic effects of arsenic. DNA damage in human lymphocytes was assessed by comet assay and fluorescence-activated DNA unwinding assay. Curcumin was analyzed in blood by high performance liquid chromatography (HPLC). Arsenic induced oxidative stress and elucidation of the antagonistic role of curcumin was done by observation on reactive oxygen species (ROS) generation, lipid peroxidation and protein carbonyl. Antioxidant enzymes like catalase, superoxide dismutase, glutathione reductase, glutathioneS-transferase, glutathione peroxidase and non-enzymatic glutathione were also analyzed. The blood samples of the endemic regions showed severe DNA damage with increased levels of ROS and lipid peroxidation. The antioxidants were found with depleted activity. Three months curcumin intervention reduced the DNA damage, retarded ROS generation and lipid peroxidation and raised the level of antioxidant activity. Thus curcumin may have some protective role against the DNA damage caused by arsenic.


Gene expression changes in human prostate carcinoma cells exposed to genotoxic and nongenotoxic aryl hydrocarbon receptor ligands.
Carcinogenic polycyclic aromatic hydrocarbons (PAHs) are known as efficient mutagens and ligands of the aryl hydrocarbon receptor (AhR), which has been suggested to play an important role in prostate carcinogenesis. In order to evaluate the complex relationship between the genotoxicity and the AhR-mediated activity of PAHs in prostate cells, we selected benzo[a]pyrene (BaP) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), as model genotoxic and nongenotoxic AhR ligands, respectively, to explore global changes in gene expression in LNCaP cells by microarray analysis. We identified 112 genes that were differentially expressed in cells treated for 24h with BaP, TCDD or both compounds. Our data indicated that the impacts of BaP and TCDD on transcriptome of LNCaP cells significantly overlap, since over 64% of significantly up-regulated genes and 47% of down-regulated genes were similarly affected by both AhR ligands. This suggested that the activation of AhR played a prominent role in the nongenotoxic effects of BaP in the prostate carcinoma cell model LNCaP. Both AhR ligands suppressed expression of genes associated with cell cycle progression, DNA replication, spindle assembly checkpoint or DNA repair, which probably occurred secondary to inhibition of cell cycle progression. In contrast, we identified Wnt5a, an important regulator of prostate cancer progression, to be induced as early as 6h after exposure to both AhR ligands. The AhR ligand-induced Wnt5a upregulation, together with other observed alterations of gene expression, may further contribute to enhanced cell plasticity of prostate carcinoma cells.


Lipids extraction from wet Chlorella pyrenoidosa sludge using recycled [BMIM]Cl.
In this study, experiments on pretreating one species of microalgae (Chlorella pyrenoidosa) using one kind of ionic liquid (IL) of [BMIM]Cl were conducted. The aim of this work is to evaluate the recycling efficacy of expensive IL solvent for effective cell disruption. It was indicated that the molecular structure of IL was stable during the recycling test. Five times antisolvent precipitation of microalgae debris after lipid extraction using methanol recovered 99.8% IL with the energy consumption of 4.46 MJ per kg dry Chlorella pyrenoidosa. The chromatography was used to separate IL and hydrolysates, resulting in the IL loss below 1.97 g per kg dry Chlorella pyrenoidosa.


Mast cells, histamine, and IL-6 regulate the selective influx of dendritic cell subsets into an inflamed lymph node.
In response to bacterial stimuli, multiple dendritic cell (DC) populations accumulate within the draining lymph node, thus enhancing opportunities for effective T cell-DC interaction. DC subpopulations, such as plasmacytoid, CD8(+), and CD11b(+) subsets, have distinct roles in determining the nature of the immune response. The mechanisms whereby individual DC subpopulations are mobilized and the extent to which these processes are linked to increases in overall lymph node cellularity have not been determined. In the current study, the mechanisms of DC subset mobilization to the draining auricular lymph node were examined after intradermal injection of Staphylococcus aureus-derived peptidoglycan. Using mast cell-deficient mice and local mast cell reconstitution, plasmacytoid and CD8(+) DC responses were shown to be mast cell dependent, whereas the CD11b(+) DC response was not. A histamine H2 receptor-dependent, CXCL9-independent pathway controlled the selective influx of both plasmacytoid and CD11b(+) DC into the lymph node, but not lymph node cellularity. In contrast, IL-6 was important for the mobilization of CD8(+) and CD11b(+) DC. TNF and IL-1 receptor were dispensable for plasmacytoid, CD11b(+), and CD8(+) DC responses. These findings provide novel opportunities for the selective mobilization of specific DC subsets to lymph nodes and demonstrate critical roles for both histamine and IL-6 in this process.


The success of failed Homo sapiens dispersals out of Africa and into Asia.
The evidence for an early dispersal of Homo sapiens from Africa into the Levant during Marine Isotope Stage 5 (MIS-5) 126-74 ka (thousand years ago) was characterized for many years as an 'abortive' expansion: a precursor to a sustained dispersal from which all extant human populations can be traced. Recent archaeological and genetic data from both western and eastern parts of Eurasia and from Australia are starting to challenge that interpretation. This Perspective reviews the current evidence for a scenario where the MIS-5 dispersal encompassed a much greater geographic distribution and temporal duration. The implications of this for tracking and understanding early human dispersal in Southeast Asia specifically are considered, and the validity of measuring dispersal success only through genetic continuity into the present is examined.


Decreased Parasympathetic Activity of Heart Rate Variability During Anticipation of Night Duty in Anesthesiology Residents.
In residency programs, it is well known that autonomic regulation is influenced by night duty due to workload stress and sleep deprivation. A less investigated question is the impact on the autonomic nervous system of residents before or when anticipating a night duty shift. In this study, heart rate variability (HRV) was evaluated as a measure of autonomic nervous system regulation. Eight residents in the Department of Anesthesiology were recruited, and 5 minutes of electrocardiography were recorded under 3 different conditions: (1) the morning of a regular work day (baseline); (2) the morning before a night duty shift (anticipating the night duty); and (3) the morning after a night duty shift. HRV parameters in the time and frequency domains were calculated. Repeated measures analysis of variance was performed to compare the HRV parameters among the 3 conditions. There was a significant decrease of parasympathetic-related HRV measurements (high-frequency power and root mean square of the standard deviation of R-R intervals) in the morning before night duty compared with the regular work day. The mean difference of high-frequency power between the 2 groups was 80.2 ms (95% confidence interval, 14.5-146) and that of root mean square of the standard deviation of R-R intervals was 26 milliseconds (95% confidence interval, 7.2-44.8), with P = .016 and .007, respectively. These results suggest that the decrease of parasympathetic activity is associated with stress related to the condition of anticipating the night duty work. On the other hand, the HRV parameters in the morning after duty were not different from the regular workday. The stress of anticipating the night duty work may affect regulation of the autonomic nervous system, mainly manifested as a decrease in parasympathetic activity. The effect of this change on the health of medical personnel deserves our concern.


Why do Purkinje cells die so easily after global brain ischemia? Aldolase C, EAAT4, and the cerebellar contribution to posthypoxic myoclonus.
The experiments strongly suggested that the reason why Purkinje cells die so easily after global brain ischemia relates to deficiencies in aldolase C and EAAT4 that allow them to survive pathologically intense synaptic input from the inferior olive after the restoration of blood flow. This conclusion is based on: (a) the remarkably tight correspondence between the regional absence of aldolase C and EAAT4 in Purkinje cells and the patterned loss of Purkinje cells after a bout of global brain ischemia; (b) the necessity of the olivocerebellar pathway for the ischemic death of Purkinje cells; and (c) the build-up of pathologically synchronous and high-frequency burst activity within the inferior olive during recovery from ischemia. Indeed, the correspondence between the absence of aldolase C and EAAT4 to sensitivity to ischemia could be demonstrated for zones of Purkinje cells as small as two neurons. A second finding was that Purkinje cells are not uniformly sensitive to transient ischemia, since they die most frequently in zones where aldolase C and EAAT4 are absent. One implication of the experiment is that factors beyond the unique synaptic and membrane properties of Purkinje cells play an important role in determining this neuron's high sensitivity to ischemia. The data strongly imply that two properties of Purkinje cells that make them susceptible to ischemic death are their reduced capability to sequester glutamate and reduced ability to generate energy during anoxia. The patterned death of Purkinje cells is sufficient to induce a form of audiogenic myoclonus, as determined with a neurotoxic dose of ibogaine. Ibogaine-induced myoclonus is recognized behaviorally as a reduced ability to habituate to a startle stimulus and resembles the myoclonic jerk of rats during recovery from a prolonged bout of global brain ischemia. Commonalities of ischemia and ibogaine-induced neurodegeneration are the intricately striped Purkinje cell loss in the posterior lobe and a nearly complete deafferentation of the lateral aspect of the fastigial nucleus from the cerebellar cortex, in particular the dorsolateral protuberance. Thus, the data point strongly to a cerebellar contribution to audiogenic myoclonus. Single-neuron electrophysiology experiments in monkeys have demonstrated that the evoked activity in the deep cerebellar nuclei occurs too late to initiate the startle response (60) and electromyography of the postischemic myoclonus of rats corroborates this view (see Chapter 31) (20). However, the nearly complete loss of GABAergic terminals in the dorsolateral protuberance after Purkinje cell death would be expected to dramatically increase its tonic firing and the background excitation of the brain-stem structures that it innervates. The fastigial nucleus innervates a large number of autonomic and motor structures in the brainstem and diencephalon, including the ventrolateral nucleus of the thalamus and the gigantocellular reticular nucleus in the medulla--structures that have been implicated in human posthypoxic myoclonus (6, 7). We propose that the posthypoxic myoclonic jerk of rats is, at least in part, due to disinhibition of the fastigial nucleus produced by patterned Purkinje cell death in the vermis. The argument is as follows: the loss of GABAergic inhibition in the fastigial nucleus after ischemia leads to diaschisis of the motor thalamus and reticular formation which, in turn, is responsible for enhanced motor excitability and myoclonus. That the audiogenic myoclonus after global brain ischemia in the rat gradually resolves over a period of 2 to 3 weeks is consistent with this view, as restoration of background excitability after CNS damage in rats has been documented to occur within this time-frame (61). Our view brings together the physiologic finding that posthypoxic myoclonus appears to originate in the sensory-motor cortices and/or reticular formation with the consistent anatomical finding of Purkinje cell loss after ischemia, and explains the puzzle of Marsden's unique cases of myoclonus associated with coeliac disease (1). Moreover, our argument is consistent with findings both in rats (62, 63) and humans (64) that damage to the vermis impairs the long-term habituation of the startle reflex. It remains to be determined whether the pathologically enhanced startle responses after vermal damage resemble brain-stem reticular or cortical myoclonus at the electrophysiologic level of analysis. What is the purpose of the regional expression of aldolase C and EAAT4 in Purkinje cells? The close correspondence between the spatial distribution of aldolase C and the parasagittal anatomy of the cerebellum (48) has led to the view that aldolase C may help specify connectivity during development. While the present experiments do not address this issue, they underscore the fact that aldolase plays a fundamental role in metabolism. Because Purkinje cells have a repressed expression of aldolase A (31), whatever role the absence of aldolase C may play during development comes at the price of metabolic frailty later in adulthood. From another point of view, aldolase C and EAAT4 appear to confer upon Purkinje cells the ability to survive their own climbing fiber. Indeed, climbing fibers form a distributed synapse that synchronously releases glutamate (or aspartate) at all levels of the dendritic tree simultaneously (65, 66). Such synchronous activation triggers calcium influx throughout the Purkinje cell dendrites at a magnitude that is unparalleled in the nervous system (12), and, thus, places an extraordinarily high metabolic demand on the Purkinje cell. The apparently reduced level of aldolase in a subpopulation of Purkinje cells provides the condition for energy failure and death during anoxia so long as the climbing fibers are intact or when climbing fiber activation is pharmacologically enhanced under normoxic conditions, such as after ibogaine (53-56). Lastly, the argument that diaschisis produced by patterned cerebellar degeneration leads to thalamo-cortical and reticular hyperexcitability agrees with C. David Marsden and his colleagues' bold demonstration of an inhibitory influence of cerebellar cortex on motor cortex in humans (67). Our anatomic data indicate that the spatially distinct zones of Purkinje cells, which are killed by global brain ischemia, may be the origin of such inhibition.


Constant-load exercise decreases the serum concentration of myeloperoxidase in healthy smokers and smokers with COPD.
There is an ongoing demand for easily accessible biomarkers related to pathophysiological processes in chronic obstructive pulmonary disease (COPD). Short-term intense exercise is known to increase the peripheral blood levels of cytokines. Therefore, we tested the potential and the repeatability of an exercise challenge to amplify seven serum biomarkers (interleukin 6 [IL6], C-reactive protein [CRP], myeloperoxidase [MPO], leukotriene B4, soluble intercellular adhesion molecule 1, soluble vascular cell adhesion molecule 1, and von Willebrand factor [VWF]) in smokers with and without COPD. Twenty-three smokers with moderate COPD (GOLD 2) and 23 sex- and age-matched healthy smokers underwent up to 30-minute submaximal, constant-load exercise (75% of maximum work load) on two occasions separated by 4 weeks (second challenge n=19/20). Serum samples were obtained before, 5 minutes after the start, at the end of exercise (maximum 30 minutes or until exhaustion), and after additional 20 minutes of rest. The median (interquartile range) exercise time until exhaustion in the two challenges was 10.0 (4.0) minutes and 10.0 (8.0) minutes in smokers with COPD and 22.0 (16.0) minutes and 26.5 (14.5) minutes in healthy smokers. The exercise challenge significantly increased the serum concentrations of IL6 and VWF, but decreased the concentrations of MPO. Healthy smokers showed a significantly greater increase (at the end of exercise compared to before exercise) in IL6 (P=0.01) and a larger decline (P=0.03) in MPO. The overall profile of the serum markers during the exercise challenge was shown to be repeatable in the second challenge. In summary, intense load exercise is capable of changing the concentration of inflammatory and endothelial function markers. Especially, the decline in the level of MPO, a marker closely related to cardiovascular risk, appears to be of clinical interest, as the exercise-induced decline might be related to the beneficial effects of physical activity in general.


Identifying applicants suitable to a career in nursing: a value-based approach to undergraduate selection.
The aim of this study was to complement existing evidence on the suitability of Multiple Mini Interviews as a potential tool for the selection of nursing candidates on to a BSc (Hons) nursing programme. This study aimed to trial the Multiple Mini Interview approach to recruitment with a group of first year nursing students (already selected using traditional interviews). Cross-sectional validation study. This paper reports on the evaluation of the participants' detailed scores from the Multiple Mini Interview stations; their original interview scores and their end of year results. This study took place in March 2015. Scores from the seven Multiple Mini Interview stations were analysed to show the internal structure, reliability and generalizability of the stations. Original selection scores from interviews and in-course assessment were correlated with the MMI scores and variation by students' age, gender and disability status was explored. Reliability of the Multiple Mini Interview score was moderate (G = 0·52). The Multiple Mini Interview score provided better differentiation between more able students than did the original interview score but neither score was correlated with the module results. Multiple Mini Interview scores were positively associated with students' age but not their gender or disability status. The Multiple Mini Interview reported in this study offers a selection process that is based on the values and personal attributes regarded as desirable for a career in nursing and does not necessarily predict academic success. Its moderate reliability indicates the need for further improvement but it is capable of discriminating between candidates and shows little evidence of bias.


Influence of health beliefs and stigma on choosing internet support groups over formal mental health services.
As the Internet has become a ubiquitous tool for health information, the use of Internet support groups for mental health concerns has grown. Despite the widespread use of these groups, little research has examined the efficacy and effectiveness of online communities for ameliorating mental health symptoms or factors that prompt people to seek online support rather than formal treatment. Our study addresses this gap in the literature by investigating Internet support group use as an alternative to formal mental health services. Logistic regression was conducted with data from the 2008 National Survey on Drug Use and Health (NSDUH) to examine relationships among treatment beliefs, practical variables such as time and affordability, stigma, and use of Internet support groups among 2,532 survey participants who reported a need for mental health treatment but were not receiving formal services. Four significant predictors of Internet support group use emerged: fear of being hospitalized or taking medication (adjusted odds ratio [AOR]=8.81, 95% confidence interval [CI]=4.25-18.27), inadequate insurance coverage (AOR=3.22, CI=1.44-7.20), age 26-34 years (AOR=.22, CI=.07-.69), and age 35 or older (AOR=.21, CI=.08-.56). Fear of coercion and the costs of traditional mental health services were important predictors of Internet support group use. The finding that inadequate insurance coverage prompted people to seek Internet support aligns with a substantial literature regarding lack of financial resources and reduced access to treatment. Individuals' fears of hospitalization and of taking medication suggested that they may view formal treatment as potentially coercive. Further work is needed to decrease public stigma regarding mental health services and the conditions under which involuntary treatment occurs.


Parent- and child-reported parenting. Associations with child weight-related outcomes.
The present study aimed to investigate associations of both parent-reported and child-perceived parenting styles and parent-reported parenting practices with child weight and weight-related behaviours. Participants were 175 children (56% female) aged between 7 and 11, and their primary caregivers (91% female), recruited through South Australian primary schools. Children completed measures of parenting style, attitude toward fruit, vegetables, and non-core food, and attraction to physical activity. Parents completed measures of parenting style and domain-specific parenting practices (feeding and activity-related practices) and reported on child dietary intake, physical activity, and sedentary behaviour. Objective height and weight measurements were taken from children, from which body mass index (BMI) was calculated. Child-reported parenting style and parent-reported parenting practices were uniquely associated with child weight-related outcomes, but styles and practices did not interact in their association with child outcomes. Child-reported parenting style was associated with child food and activity attitudes, whereas parent-reported parenting style was not associated with child outcomes. The findings of the present study generally support the recommendation of a parenting style high in demandingness and responsiveness for supporting healthy child weight-related behaviours, along with appropriate domain-specific practices. The child's perspective should be incorporated into research involving child outcomes wherever possible.


Projected impact of monoclonal anti-endotoxin antibody therapy.
The goals of this study were to evaluate the criteria for administration of HA-1A monoclonal antibody therapy from the HA-1A trial in patients with suspected gram-negative bacteremia and to evaluate the accuracy with which Bone's criteria for sepsis syndrome identify patients with gram-negative bacteremia. This prospective cohort study included 1509 episodes in which hospitalized patients had blood cultures performed in an urban tertiary-care hospital. The main outcome measures were gram-negative bacteremia and gram-negative sepsis. Of 1509 episodes, 115 (8%) represented bacteremia and 40 (3%) included gram-negative rods. Of these 40 patients, nine died in the hospital, including five patients who had gram-negative sepsis; all five had another rapidly fatal disease. Using criteria for treatment and exclusions from the HA-1A trial, three of the patients with gram-negative bacteremia would have been treated, while at least 52 patients without gram-negative bacteremia might have received HA-1A therapy (positive predictive value of criteria, 5.5%). Of the 1509 episodes, sepsis syndrome as defined by Bone was present in 34 (2.3%). While 32 of the 34 patients had suspected gram-negative bacteremia, only five had blood cultures positive for gram-negative bacteria. In this population, current criteria for administration of monoclonal anti-endotoxin antibody therapy were not sensitive or specific for gram-negative bacteremia, and many patients with gram-negative sepsis were too ill from other conditions to benefit. Indiscriminate use of these therapies could thus be costly yet yield few benefits. To identify patients who should receive novel therapies, better risk-stratification methods and cost-effectiveness analysis are needed.


Echocardiographic Image Quality Deteriorates with Age in Children and Young Adults with Duchenne Muscular Dystrophy.
Advances in medical care for patients with Duchenne muscular dystrophy (DMD) have resulted in improved survival and an increased prevalence of cardiomyopathy. Serial echocardiographic surveillance is recommended to detect early cardiac dysfunction and initiate medical therapy. Clinical anecdote suggests that echocardiographic quality diminishes over time, impeding accurate assessment of left ventricular systolic function. Furthermore, evidence-based guidelines for the use of cardiac imaging in DMD, including cardiac magnetic resonance imaging (CMR), are limited. The objective of our single-center, retrospective study was to quantify the deterioration in echocardiographic image quality with increasing patient age and identify an age at which CMR should be considered. We retrospectively reviewed and graded the image quality of serial echocardiograms obtained in young patients with DMD. The quality of 16 left ventricular segments in two echocardiographic views was visually graded using a binary scoring system. An endocardial border delineation percentage (EBDP) score was calculated by dividing the number of segments with adequate endocardial delineation in each imaging window by the total number of segments present in that window and multiplying by 100. Linear regression analysis was performed to model the relationship between the EBDP scores and patient age. Fifty-five echocardiograms from 13 patients (mean age 11.6 years, range 3.6-19.9) were systematically reviewed. By 13 years of age, 50% of the echocardiograms were classified as suboptimal with ≥30% of segments inadequately visualized, and by 15 years of age, 78% of studies were suboptimal. Linear regression analysis revealed a negative correlation between patient age and EBDP score (r = -2.49, 95% confidence intervals -4.73, -0.25; p = 0.032), with the score decreasing by 2.5% for each 1 year increase in age. Echocardiographic image quality declines with increasing age in DMD. Alternate imaging modalities may play a role in cases of poor echocardiographic image quality.


[Risk of transmission of infectious diseases by transfusion].
In obstetric patients transfusion is a common procedure, it has many advantages but it also has severe risks. Since the observation that human immunodeficiency virus (HIV) infection is transmitted by transfusion, the number of preventive measures to reduce the infectious diseases transmission by this procedure has increased. The microorganisms that can be transmitted through transfusion include: human T lymphotropic virus (HTLV) I and II, hepatitis B virus, hepatitis C virus, hepatitis D virus, hepatitis G virus, HIV, cytomegalovirus, Treponema pallidum, Barucella sp, Toxoplasma gondii, Plasmodium sp, and Trypanosoma cruzi. The most important measure for reduce transfusion risks is the appropriate and careful use of this procedure. This article review transfusion's indication, describe the infectious diseases commonest transmitted by transfusion and analyze the preventive measures to put in practice.


Impact of add-back FSH on human and mouse prostate following gonadotropin ablation by GnRH antagonist treatment.
During androgen ablation in prostate cancer by the standard gonadotropin-releasing hormone (GnRH) agonist treatment, only luteinizing hormone (LH) is permanently suppressed while circulating follicle-stimulating hormone (FSH) rebounds. We explored direct prostatic effects of add-back FSH, after androgen ablation with GnRH antagonist, permanently suppressing both gonadotropins. The effects of recombinant human (rFSH) were examined in mice treated with vehicle (controls), GnRH antagonist degarelix (dgx), dgx + rFSH, dgx + flutamide, or dgx + rFSH + flutamide for 4 weeks. Prostates and testes size and expression of prostate-specific and/or androgen-responsive genes were measured. Additionally, 33 young men underwent dgx-treatment. Seventeen were supplemented with rFSH (weeks 1-5), and all with testosterone (weeks 4-5). Testosterone, gondotropins, prostate-specific antigen (PSA), and inhibin B were measured. In dgx and dgx + flutamide treated mice, prostate weight/body weight was 91% lower than in controls, but 41 and 11%, respectively, was regained by rFSH treatment (P = 0.02). The levels of seminal vesicle secretion 6, Pbsn, Nkx3.1, beta-microseminoprotein, and inhibin b were elevated in dgx + rFSH-treated animals compared with only dgx treated (all P < 0.05). In men, serum inhibin B rose after dgx treatment but was subsequently suppressed by testosterone. rFSH add-back had no effect on PSA levels. These data provide novel evidence for the direct effects of FSH on prostate size and gene expression in chemically castrated mice. However, in chemically castrated men, FSH had no effect on PSA production. Whether FSH effects on the prostate in humans also require suppression of the residual adrenal-derived androgens and/or a longer period of rFSH stimulation, remains to be explored.


An in vivo analysis of the localisation and interactions of human p66 DNA polymerase delta subunit.
DNA polymerase delta is essential for eukaryotic DNA replication and also plays a role in DNA repair. The processivity of this polymerase complex is dependent upon its interaction with the sliding clamp PCNA and the polymerase-PCNA interaction is largely mediated through the p66 polymerase subunit. We have analysed the interactions of the human p66 DNA polymerase delta subunit with PCNA and with components of the DNA polymerase delta complex in vivo. Using the two-hybrid system, we have mapped the interaction domains for binding to the p50 polymerase delta subunit and with PCNA to the N-terminus and the C-terminus of p66, respectively. Co-immunoprecipitation experiments confirm that these interaction domains are functional in vivo. Expression of EGFP-p66 shows that it is a nuclear protein which co-localises with PCNA throughout the cell cycle. p66 is localised to sites of DNA replication during S phase and to repair foci following DNA damage. We have identified a functional nuclear localisation sequence and shown that localisation to replication foci is not dependent upon active nuclear import. Sub-domains of p66 act as dominant negative suppressors of colony formation, suggesting that p66 forms an essential structural link between the p50 subunit and PCNA. Analysis of the C-terminal PCNA binding motif shows that deletion of the QVSITGFF core motif results in a reduced affinity for PCNA, while deletion of a further 20 amino acids completely abolishes the interaction. A reduced affinity for PCNA correlates with reduced targeting to replication foci. We have confirmed the p66-PCNA interaction in vivo using fluorescence resonance energy transfer (FRET) techniques. We have defined the regions of p66 required for its interaction with PCNA and the p50 polymerase subunit. We demonstrate a functional link between PCNA interaction and localisation to replication foci and show that there is a direct interaction between p66 and PCNA in living cells during DNA replication. The dominant negative effect upon growth resulting from expression of p66 sub-domains confirms that the p66-PCNA interaction is essential in vivo.


The clinical management and outcome of nail salon-acquired Mycobacterium fortuitum skin infection.
Nontuberculous mycobacterial infections are becoming more common. Recently, Mycobacterium fortuitum and other rapidly growing mycobacteria have been found to cause severe skin and soft-tissue infections in association with nail salon whirlpool footbaths. We recently investigated a large outbreak of M. fortuitum furunculosis among women who received pedicures at a single nail salon. To better define the clinical course of such infections, we collected clinical details from physicians who were treating outbreak patients. We constructed multivariable linear models to evaluate the effect of antibiotic treatment on disease duration. Sixty-one patients were included in the investigation. The mean disease duration was 170 days (range, 41-336 days). Forty-eight persons received antibiotic therapy for a median period of 4 months (range, 1-6 months), and 13 persons were untreated. Isolates were most susceptible to ciprofloxacin and minocycline. Early administration of therapy was associated with shorter duration of disease only in persons with multiple boils (P<.01). One untreated, healthy patient had lymphatic disease dissemination.


Tracking in anatomic pathology.
Bar code-based tracking solutions, long present in clinical pathology laboratories, have recently made an appearance in anatomic pathology (AP) laboratories. Tracking of AP "assets" (specimens, blocks, slides) can enhance laboratory efficiency, promote patient safety, and improve patient care. Routing of excess clinical material into research laboratories and biorepositories are other avenues that can benefit from tracking of AP assets. Implementing tracking is not as simple as installing software and turning it on. Not all tracking solutions are alike. Careful analysis of laboratory workflow is needed before implementing tracking to assure that this solution will meet the needs of the laboratory. Such analysis will likely uncover practices that may need to be modified before a tracking system can be deployed. Costs that go beyond simply that of purchasing software will be incurred and need to be considered in the budgeting process. Finally, people, not technology, are the key to assuring quality. Tracking will require significant changes in workflow and an overall change in the culture of the laboratory. Preparation, training, buy-in, and accountability of the people involved are crucial to the success of this process. This article reviews the benefits, available technology, underlying principles, and implementation of tracking solutions for the AP and research laboratory.


Case report: A proposed role for cardiopulmonary exercise testing in detecting cardiac dysfunction in asymptomatic at-risk adolescents.
Noninvasive cardiopulmonary exercise testing (CPET) provides the valuable capacity to analyze pulmonary gas exchange and cardiovascular responses that can be used to differentiate normal cardiopulmonary responses from abnormal. This case report highlights a proposed role for CPET in identifying potential cardiac pathologies in at-risk adolescents. An abnormal CPET response in an asymptomatic adolescent revealed a family history of early-age CAD. The significance of the abnormal CPET response was further supported by the presence of an elevated concentration of circulating high sensitivity C-reactive protein (hs-CRP). These findings emphasize the importance of a thorough clinical evaluation in at-risk adolescents, as CPET can aid in the early detection and management of cardiac pathologies, especially when combined with other relevant biomarkers such as plasma hs-CRP concentration, which can further suggest underlying pathology. Management considerations using serial CPET evaluations are recommended. Thus, CPET abnormalities combined with elevated hs-CRP should be taken seriously and provide justification for further evaluation and monitoring in adolescents at risk for cardiovascular disease.


Control of neuronal persistent activity by voltage-dependent dendritic properties.
Neural integrators and working memory rely on persistent activity, a widespread neural phenomenon potentially involving persistent sodium conductances. Using a unique combination of voltage-clamp, dynamic-clamp, and frequency-domain techniques, we have investigated the role of voltage-dependent conductances on the dendritic electrotonic structure of neurons of the prepositus hypoglossi nucleus (PHN), which is known to be involved in oculomotor integration. The PHN contains two main neuronal populations: type B neurons with a double afterhyperpolarization and type D neurons, which not only are oscillatory but also have a greater electrotonic length than that of type B neurons. The persistent sodium conductance is present in all PHN neurons, although its effect on the dynamic electrotonic structure is shown to significantly differ in the two major cell types present in the nucleus. The electrotonic differences are such that the persistent sodium conductance can be almost perfectly manipulated in a type B neuron using an on-line dynamic clamp to add or subtract virtual sodium ion channels. The dynamic-clamp results are confirmed by data-fitted models, which suggest that the persistent sodium conductance has two different roles depending on its somatic versus dendritic location: perisomatic conductances could play a major role in maintaining action potential discharge and dendritic conductances would be more involved in other computational properties, such as those involving remote synaptic processing or bistable events.


Antiprothrombin antibodies: a comparative analysis of homemade and commercial methods. A collaborative study by the Forum Interdisciplinare per la Ricerca nelle Malattie Autoimmuni (FIRMA).
Prothrombin (PT) is a target for antibodies with lupus anticoagulant (LA) activity, suggesting the possible application of anti-prothrombin antibody (aPT) assays in patients with antiphospholipid syndrome (APS). Different methods - both homemade and commercial - for the detection of aPT are available, but they seem to produce conflicting results. The purpose of this study was to compare the performance of different assays on a set of well-characterized serum samples. Sera were gathered from 4 FIRMA institutions, and distributed to 15 participating centres. Forty-five samples were from patients positive for LA and/or anticardiolipin antibodies (aCL) with or without APS, and 15 were from rheumatoid arthritis (RA) patients negative for antiphospholipid antibodies. The samples were evaluated for IgG and IgM antibodies using a homemade direct aPT assay (method 1), a homemade phosphatidylserine-dependent aPT assay (aPS/PT, method 2), and two different commercial kits (methods 3 and 4). In addition, a commercial kit for the detection of IgG-A-M aPT (method 5) was used. Inter-laboratory results for the 5 methods were not always comparable when different methods were used. Good inter-assay concordance was found for IgG antibodies evaluated using methods 1, 3, and 4 (Cohen k > 0.4), while the IgM results were discordant between assays. In patients with thrombosis and pregnancy losses, method 5 performed better than the others. While aPT and aPS/PT assays could be of interest from a clinical perspective, their routine performance cannot yet be recommended because of problems connected with the reproducibility and interpretation of the results.


Medial prefrontal cortex neuronal activation and synaptic alterations after stress-induced reinstatement of palatable food seeking: a study using c-fos-GFP transgenic female rats.
Relapse to maladaptive eating habits during dieting is often provoked by stress and there is evidence for a role of ovarian hormones in stress responses and feeding. We studied the role of these hormones in stress-induced reinstatement of food seeking and medial prefrontal cortex (mPFC) neuronal activation in c-fos-GFP transgenic female rats, which express GFP in strongly activated neurons. Food-restricted ovariectomized or sham-operated c-fos-GFP rats were trained to lever-press for palatable food pellets. Subsequently, lever-pressing was extinguished and reinstatement of food seeking and mPFC neuronal activation was assessed after injections of the pharmacological stressor yohimbine (0.5-2 mg/kg) or pellet priming (1-4 noncontingent pellets). Estrous cycle effects on reinstatement were also assessed in wild-type rats. Yohimbine- and pellet-priming-induced reinstatement was associated with Fos and GFP induction in mPFC; both reinstatement and neuronal activation were minimally affected by ovarian hormones in both c-fos-GFP and wild-type rats. c-fos-GFP transgenic rats were then used to assess glutamatergic synaptic alterations within activated GFP-positive and nonactivated GFP-negative mPFC neurons following yohimbine-induced reinstatement of food seeking. This reinstatement was associated with reduced AMPA receptor/NMDA receptor current ratios and increased paired-pulse facilitation in activated GFP-positive but not GFP-negative neurons. While ovarian hormones do not appear to play a role in stress-induced relapse of food seeking in our rat model, this reinstatement was associated with unique synaptic alterations in strongly activated mPFC neurons. Our paper introduces the c-fos-GFP transgenic rat as a new tool to study unique synaptic changes in activated neurons during behavior.


Sexual selection and inbreeding: Two efficient ways to limit the accumulation of deleterious mutations.
Theory and empirical data showed that two processes can boost selection against deleterious mutations, thus facilitating the purging of the mutation load: inbreeding, by exposing recessive deleterious alleles to selection in homozygous form, and sexual selection, by enhancing the relative reproductive success of males with small mutation loads. These processes tend to be mutually exclusive because sexual selection is reduced under mating systems that promote inbreeding, such as self-fertilization in hermaphrodites. We estimated the relative efficiency of inbreeding and sexual selection at purging the genetic load, using 50 generations of experimental evolution, in a hermaphroditic snail (Physa acuta). To this end, we generated lines that were exposed to various intensities of inbreeding, sexual selection (on the male function), and nonsexual selection (on the female function). We measured how these regimes affected the mutation load, quantified through the survival of outcrossed and selfed juveniles. We found that juvenile survival strongly decreased in outbred lines with reduced male selection, but not when female selection was relaxed, showing that male-specific sexual selection does purge deleterious mutations. However, in lines exposed to inbreeding, where sexual selection was also relaxed, survival did not decrease, and even increased for self-fertilized juveniles, showing that purging through inbreeding can compensate for the absence of sexual selection. Our results point to the further question of whether a mixed strategy combining the advantages of both mechanisms of genetic purging could be evolutionary stable.


Effect of Different Milk Diet on the Level of Fecal Calprotectin in Very Preterm Infants.
Objective: To evaluate the course of fecal calprotectin (FC) in very preterm infants over the first 15 days of life in relation to the type of milk diet. Methods: This study was part of a randomized controlled trial comparing two different ways of integrating the own mother's milk (OMM) for the evaluation of feeding tolerance in very preterm infants. In infants with gestational age of ≤ 32 weeks randomized to receive preterm formula (PF group) or pasteurized donor human milk (PDHM group) as a supplement to the OMM insufficient or unavailable, FC level was planned to be measured at the first meconium passage and at days 8 and 15 of life (T0, T1, and T2, respectively). Results: FC data were available for all the 70 infants randomized, 35 in the PF group, and 35 in the PDHM group. The mean FC levels were similar in the two study groups at T0 and T1, whereas they were significantly higher in the PF group than the PDHM group at T2. FC values decreased over the first week of life in both groups and significantly increased over the second week of life only in the PF group. Conclusions: Our study demonstrates a significant increase in FC levels when PF is used as a supplement to the OMM compared to the use of PDHM. Further studies are needed to establish if the higher FC levels in infants receiving PF are the expression of a normal immunological maturation rather than an initial inflammatory process.


[Polymorphism of Platelet Specific Antigens (HPA-1-5, 15) in Han Donors in the North Area of Henan Province].
To study the gene polymorphism distribution characteristics of human platelet HPA-1-5 and 15 blood group antigens and construct a certain scale of platelet HPA database in the north area of Henan Province so as to provide platelet apheresis for clinical departments. Using polymerase chain reaction with sequence-specific primers (PCR-SSP), the genotyping of HPA-1-5 and 15 system was carried out; the periperal blood of 500 healthy Han donors in north area of Henan Province was collected randomly, the gene and genotype frequencies were detected by direct counting method, and the population distribution frequncy of HPA genes was analyzed by Hardy-Weinberg balance test, and compared with other regions and ethnics by using χ(2) test. There was statistically significant (P < 0.05) of increase HPA-3b and HPA-5a in North area of Henan Province, compared with Chinese Han population; the HPA-3b and 5a increase and HPA-2a decrease were statistically significant (P < 0.05), compared with Ethnic minority of China. There was partly increase of HPA-1a, 2a, 3a and 5a, compared with different regions and ethnic in abroad. HPA allele genes of 500 Han donors in the North area of Henan Province were as follows: 0.985 and 0.015 for 1a and 1b; 0.924 and 0.076 for 2a and 2b; 0.469 and 0.531 for 3a and 3b; 1.000 and 1.000 for 4a and 5a; 0.532 and 0.468 for 15a and 15b, respectively. HPA allele gene frequencies were 1aa0.970, 1ab0.030; 2aa0.848, 2ab0.152; 3aa0.222, 3ab0.494, 3bb0.284; 4aa1.000; 5aa1.000; 15aa0.282, 15ab0.500, 15bb0.218. Compared with other regions and ethnic, HPA gene frequencies partly had statistical significance. Distribution of HPA allele frequencies in the North area of Henan province is in accordence with the Hardy-Weinberg law. There are race and regional differences in HPA allele gene frequencies, compared with other regions and countries. And the HPA systems HPA-3 and 15 display the genetic polymorphisms, which provides a theoretical basis for the relevant research of the same type platelet infusion and alloimmune thrombocytopenia.


Multivariate left-censored Bayesian model for predicting exposure using multiple chemical predictors.
Environmental health exposures to airborne chemicals often originate from chemical mixtures. Environmental health professionals may be interested in assessing exposure to one or more of the chemicals in these mixtures, but often exposure measurement data are not available, either because measurements were not collected/assessed for all exposure scenarios of interest or because some of the measurements were below the analytical methods' limits of detection (i.e. censored). In some cases, based on chemical laws, two or more components may have linear relationships with one another, whether in a single or in multiple mixtures. Although bivariate analyses can be used if the correlation is high, often correlations are low. To serve this need, this paper develops a multivariate framework for assessing exposure using relationships of the chemicals present in these mixtures. This framework accounts for censored measurements in all chemicals, allowing us to develop unbiased exposure estimates. We assessed our model's performance against simpler models at a variety of censoring levels and assessed our model's 95% coverage. We applied our model to assess vapor exposure from measurements of three chemicals in crude oil taken on the Ocean Intervention III during the Deepwater Horizon oil spill response and clean-up.


The topography of the surface of potato virus X: tritium planigraphy and immunological analysis.
Thermally activated tritium atoms were used to probe the surface topography of the coat protein of potato virus X (PVX) potexvirus. The accessibility profile of amino acid residues in the polypeptide chain was determined from data on the intramolecular distribution of tritium label in the PVX coat protein. Tryptic peptides T1 and T2, as well as parts of peptides T3 and T5, from the PVX particles were all located in the N-terminal region of the PVX coat protein and were accessible to tritium labelling, whereas the C-terminal region of the coat protein was practically inaccessible to it. Indirect ELISA and immunoblotting with two PVX-specific monoclonal antibodies confirmed that the N terminus of the coat protein (residues 1 to 56) was exposed on the virus surface, and furthermore that this region forms a highly immunogenic virus-specific antigenic region. The data obtained support the spatial model of PVX, in which the N-terminal amino acids of the coat protein are exposed at the particle surface, and the C-terminal region is buried in the particle. The spatial organization of the PVX coat proteins differs from the model proposed for other filamentous plant viruses such as potyviruses and tobamoviruses where both the N and C termini of the coat protein are located at the particles' surface.


Puncture performance tests reveal distinct feeding modes in pinniped teeth.
Marine mammals have undergone a dramatic series of morphological transformations throughout their evolutionary history that facilitated their ecological transition to life in the water. Pinnipeds are a diverse clade of marine mammals that evolved from terrestrial carnivorans in the Oligocene (∼27 million years ago). However, pinnipeds have secondarily lost the dental innovations emblematic of mammalian and carnivoran feeding, such as a talonid basin or shearing carnassials. Modern pinnipeds do not masticate their prey, but can reduce prey size through chopping behavior. Typically, small prey are swallowed whole. Nevertheless, pinnipeds display a wide breadth of morphology of the post-canine teeth. We investigated the relationship between dental morphology and pinniped feeding by measuring the puncture performance of the cheek-teeth of seven extant pinniped genera. Puncture performance was measured as the maximum force and the maximum energy required to puncture a standardized prey item (Loligo sp.). We report significant differences in the puncture performance values across the seven genera, and identify three distinct categories based on cheek-teeth morphology and puncture performance: effective, ineffective and moderate puncturers. In addition, we measured the overall complexity of the tooth row using two different metrics, orientation patch count rotated (OPCR) and relief index (RFI). Neither metric of complexity predicted puncture performance. Finally, we discuss these results in the broader context of known pinniped feeding strategies and lay the groundwork for subsequent efforts to explore the ecological variation of specific dental morphologies.