[Electroacupuncture Combined with Intracerebral Injection of VEGF Improves Neurological Dysfunction Possibly by Down-regulating Expression of Endoplasmic Reticulum Stress Related Proteins ATF 6, etc. in Cerebral Ischemia-reperfusion Injury Rats].
To observe the effect of electroacupuncture (EA) and EA combined with intracerebral injection of vascular endothelial growth factor (VEGF) on endoplasmic reticulum stress (ERS) related proteins and genes as activating transcription factor (ATF 6), inositol requiring enzyme-1 (IRE 1), CCAAT/enhancer binding protein homologous protein (CHOP), X box-binding protein-1 (XBP 1) of cerebral ischemia reperfusion injury (CIRI) rats, so as to study its repair effect for CIRI. Forty male SD rats were equally and randomly divided into 5 groups: sham operation, model, EA, VEGF and EA+VEGF groups (n=8). The CIRI model was established by occlusion of the middle cerebral artery (MCAO) with thread embolism method. For rats of the sham operation group, the right common carotid artery was isolated without MCAO. EA (2 Hz/100 Hz, 1-3 mA) was applied to "Baihui" (GV 20), left "Quchi" (LI 11) and left "Zusanli" (ST 36) for 30 min, once a day for 14 days. For rats of the VEGF and EA+VEGF groups, 10 µL VEGF (0.025 µg/µL) was injected into the lateral ventricle 24 h after successful modeling. The rats' neurological function was assessed by using the modified neurological severity score (mNSS), and the histopathological changes of cerebral tissue were observed by Nissl staining method. The expression levels of ERS related proteins and genes ATF 6, IRE 1, XBP 1 and CHOP were determined by western blot (WB) and fluorescent quantitative PCR, separately. After modeling, the level of mNSS was significantly higher in the model group than in the sham operation group (P<0.05), and the number of Nissl bodies was markedly lower in the model group than in the sham operation group (P<0.05). Following the treatment, the mNSS was significantly lower in the EA, VEGF and EA+VEGF groups than in the model group (P<0.05), and the numbers of Nissl bodies were obviously higher in the EA, VEGF and EA+VEGF groups than in the model group (P<0.05), suggesting an improvement of neurological dysfunction and a repair of the injured cerebral tissue after the treatment. The levels of CIRI-induced increase of mNSS and CIRI-induced decrease of the number of Nissl bodies in the EA+VEGF group were respectively remarkably lower or higher than those of the simple EA and simple VEGF groups (P<0.05). WB and PCR showed that the expression levels of ATF 6, IRE 1, XBP1 and CHOP proteins and genes were notably higher in the model group than in the sham operation group (P<0.05), and considerably lower in the EA, VEGF and EA+VEGF groups than in the model group (P<0.05). Comparison among the three treatment groups showed that after the treatment, the expression levels of ATF 6, IRE 1, XBP1 and CHOP proteins and genes were obviously lower in the EA+VEGF group than in the EA and VEGF groups (P<0.05). EA and EA plus intracerebral microinjection of VEGF can improve neurological function and promote cerebral tissue repair in CIRI rats, which is associated with their effects in down-regulating the expression of ERS related proteins ATF 6, IRE 1, XBP1 and CHOP. The effect of EA+VEGF is superior to that of simple EA and simple VEGF.


Osteopoietin-humoral induction factor in osteogenesis.
A heat-stable, glycoprotein-like material, osteopoietin, produced during bone marrow regeneration, has been shown to induce bone formation when implanted in the rat eye. The material was separated by ultrasonic treatment or by acid buffer (pH 3-5) from sponges implanted in the marrow. The extracted material free of bone or cell solids, induced bone formation in the anterior eye chamber of the rat, whereas the cell solids and control sponges similarly implanted did not.


Comparison of Laser and Conventional Lancing Devices for Blood Glucose Measurement Conformance and Patient Satisfaction in Diabetes Mellitus.
Self-monitoring of capillary blood glucose is important for controlling diabetes. Recently, a laser lancing device (LMT-1000) that can collect capillary blood without skin puncture was developed. We enrolled 150 patients with type 1 or 2 diabetes mellitus. Blood sampling was performed on the same finger on each hand using the LMT-1000 or a conventional lancet. The primary outcome was correlation between glucose values using the LMT-1000 and that using a lancet. And we compared the pain and satisfaction of the procedures. The capillary blood sampling success rates with the LMT-1000 and lancet were 99.3% and 100%, respectively. There was a positive correlation (r=0.974, P<0.001) between mean blood glucose levels in the LMT-1000 (175.8±63.0 mg/dL) and conventional lancet samples (172.5±63.6 mg/dL). LMT-1000 reduced puncture pain by 75.0% and increased satisfaction by 80.0% compared to a lancet. We demonstrated considerable consistency in blood glucose measurements between samples from the LMT-1000 and a lancet, but improved satisfaction and clinically significant pain reduction were observed with the LMT-1000 compared to those with a lancet.


Application of response surface methodology to the temperature fluctuation suppression structure in the cryostats.
The cryocooler-based cryostat typically suffers from an intrinsic 200 mK temperature oscillation originating from the periodic variation of the cryocooler's working fluid. In this paper, a numerical study is performed to investigate the impact of a thermal link (a temperature fluctuation suppression structure)'s geometric parameters on a cryostat's performance. An optimization model is developed to minimize a cryostat flange's temperature fluctuation and deviation. We considered three factors during the analysis: the number of the thermal link wires n, the length of the thermal link l, and the radius of the thermal link wires r. Two primary evaluation measures are the temperature fluctuation Tp-p and the temperature deviation of the flange Ri. The results are analyzed using Response Surface Methodology. The final predicted optimum combination of geometrical parameters for the thermal link is n = 8, l = 36 mm, and r = 0.8 mm. The optimization results are in good agreement with our model, and the deviations in predicted values are less than 1.6%. The model and results presented here to optimize the thermal link provide helpful guidance for cryostat optimization in experiments.


Pre-conditioning to global cerebral ischemia changes hippocampal acetylcholinesterase in the rat.
This study shows the effect of transient global cerebral ischemia (ISC) on hippocampal acetylcholinesterase (AChE) activity. Naive adult Wistar rats received either a brief (2 min) or a long (10 min) ischemic episode by the four-vessel occlusion method. Pre-conditioned rats received double ischemia: a 10 min episode inflicted 24 h after a 2 min event, a condition known to confer cytoprotection to CA1 pyramidal cells of hippocampus. 2 min of ischemia caused an increase in acetylcholinesterase activity both immediately and 30 min after the episode, however enzyme activity was significantly decreased after 24 h of reperfusion. 10 min of ischemia caused an increase in activity both 60 min and 24 h after ischemia. Conversely, pre-conditioned rats displayed lower activity both immediately and 60 min after ischemia. Our results suggest that: a) neuronal death, that follows 10 min of ischemia, is associated to a late increase in acetylcholinesterase activity; b) pre-conditioning is related to diminished acetylcholinesterase activity. This is in agreement with previous evidence that acetylcholinesterase inhibition and maintenance of acetylcholine levels are beneficial for cell surviving after cerebral ischemia.


Computed tomography before transfer to a level I pediatric trauma center risks duplication with associated increased radiation exposure.
Community hospitals commonly obtain computed tomographic (CT) imaging of pediatric trauma patients before triaging to a level I pediatric trauma center (PTC). This practice potentially increases radiation exposure when imaging must be duplicated after transfer. A retrospective review of our level 1 PTC registry from January 1, 2004, to December 31, 2006, was conducted. Level I and II trauma patients were grouped based on whether they had undergone outside CT examination (head and/or abdomen) at a referring hospital (group 1) or received initial CT examination at our institution (group 2). Subgroups were analyzed based on whether duplicate CT examination was required at our PTC (Fischer's Exact test). A duplicate CT scan (within 4 hours of transfer) was required in 91% (30/33) of group 1 transfer patients, whereas no group 2 patient required a duplicate scan (0/55; P < .0001). There was no significant difference within the groups for weight, age, or intensive care unit length of stay. A significant number of pediatric trauma patients who receive CT scans at referring hospitals before transfer to our level I PTC require duplicate scans of the same anatomical field(s) after transfer, exposing them to increase potential clinical risk and cost.


Characterization of Botrytis cinerea Isolates From Grape Vineyards in China.
One hundred thirty-five single-spore isolates were collected from grape vineyards from 15 provinces or autonomous regions belonging to five viticulture climatic zones in China. All the isolates were identified as Botrytis cinerea based on their morphological and molecular characters. The 135 isolates were all heterothallic isolates. Seventy-one isolates belonged to the MAT1-1 type and 64 were characterized to MAT1-2 type. All the isolates studied belonged to Group II based on PCR-RFLP of the Bc-hch locus. The four TE genotypes, transposa, Boty-only, Flipper-only, and vacuma, comprised 51.9%, 33.3%, 10.4%, and 4.5%, respectively, of the total population. The frequency of transposa was highest in the total population and the most of any subpopulation (each viticulture climatic zone), and Boty-only was highest in warm areas (46.2%). Vacuma was mainly distributed in northern China, although in small amounts, and Flipper-only was mainly was distributed in humid tropical areas (42.9%). A microsatellite analysis of B. cinerea populations was performed to assess the genetic population structure. A total of 127 different MLGs were identified among 135 B. cinerea isolates, with a genotypic diversity of 0.9991. The transposa population isolates showed higher genetic diversity than other populations. Pairwise tests of genetic differentiation among four TE-type populations yielded generally low to high Gst values. All isolates belonged to two genetic clusters. The population microsatellite diversity and genetic structure had a certain correlation with the TE type and geographic origin. This is the first report of the genotypic diversity of B. cinerea isolates from grape vineyards across China.


Synaptic and nonsynaptic localization of GABAA receptors containing the alpha5 subunit in the rat brain.
The alpha5 subunit of the GABA(A) receptors (GABA(A)Rs) has a restricted expression in the brain. Maximum expression of this subunit occurs in the hippocampus, cerebral cortex, and olfactory bulb. Hippocampal pyramidal cells show high expression of alpha5 subunit-containing GABA(A)Rs (alpha5-GABA(A)Rs) both in culture and in the intact brain. A large pool of alpha5-GABA(A)Rs is extrasynaptic and it has been proposed to be involved in the tonic GABAergic inhibition of the hippocampus. Nevertheless, there are no studies on the localization of the alpha5-GABA(A)Rs at the electron microscope (EM) level. By using both immunofluorescence of cultured hippocampal pyramidal cells and EM postembedding immunogold of the intact hippocampus we show that, in addition to the extrasynaptic pool, there is a pool of alpha5-GABA(A)Rs that concentrates at the GABAergic synapses in dendrites of hippocampal pyramidal cells. The results suggest that the synaptic alpha5-GABA(A)Rs might play a role in the phasic GABAergic inhibition of pyramidal neurons in hippocampus and cerebral cortex.


No genetic linkage detected for schizophrenia to Xq27-q28.
The hypothesis that at least a subgroup of familial cases of schizophrenia could be due to a genetic defect on the X chromosome is supported by the observation of an excess of X-chromosome aneuploidies (XXX and XXY) among populations of patients with psychosis. The distal long arm, Xq27-q28, is a candidate region where linkage has been claimed to manic-depressive disorder and a fragile site has been associated with schizophrenia spectrum disorders. The present study excluded linkage to a large part of this region using four polymorphic probes and multipoint lod-score analysis in 10 families with multiple members with schizophrenia.


Effect of using triclosan-impregnated suture for incisional closure on surgical site infection and inflammation following tibial plateau leveling osteotomy in dogs.
To compare surgical site infection and inflammation rates between the use of nonimpregnated (polydioxanone and poliglecaprone 25) versus triclosan-impregnated (polydioxanone and poliglecaprone 25) suture for incisional closure in dogs undergoing a standardized orthopedic procedure (tibial plateau leveling osteotomy [TPLO]). Retrospective cohort study. 283 dogs that underwent TPLO between November 2005 and December 2009. Medical records were reviewed for age; body weight; body condition score; use of propofol; perioperative and postoperative administration of antimicrobials; presence of a preoperative infection; use of a jig; technique of joint exploration; type of suture material (triclosan impregnated vs nonimpregnated) used to close the pes anserinus, subcutaneous layer, and subcuticular layer; use of staples or suture to close the skin; and surgery and anesthesia durations. The outcome variables were surgical site inflammation and infection. Rates of infection and inflammation did not differ between surgeries for which triclosan-impregnated suture was used (n = 159 [8.8%, and 18.8%, respectively]) and those for which nonimpregnated suture was used (112 [10.7% and 15.2%, respectively]). The use of staples, compared with suture, to close the skin significantly decreased the inflammation rate. Compared with in vitro conditions, in vivo conditions (where the environment is not controlled and triclosan may elute more quickly from the suture) may decrease the antibacterial effectiveness of triclosan-impregnated suture. On the basis of our findings, triclosan-impregnated sutures did not seem to provide an additional benefit for clinical use and cannot be strongly recommended for elective orthopedic procedures in veterinary medicine.


"It's a fight to get anything you need" - Accessing care in the community from the perspectives of people with multimorbidity.
There is a growing interest in redesigning health-care systems to better manage the increasing numbers of people with multimorbidity. Knowing how patients experience health-care delivery and what they need from the health-care system are critical pieces of evidence that can be used to guide health system reforms. The purpose of this study was to understand the challenges patients with multimorbidity face in accessing care in the community, and the implications for patients and their families. A secondary analysis of qualitative data was conducted on semi-structured interviews with 116 patients who were receiving care in an urban rehabilitation facility in 2011. Exploratory interpretive analysis was used to identify themes about access to care. Challenges occurred at two levels: at the health system level and at the individual (patient) level. Issues at the health system level fell into two broad categories: availability of services (failing to qualify, coping with wait times, struggling with scarcity and negotiating the location of care) and service delivery (unreliable care, unmet needs, incongruent care and inflexible care). Challenges at the patient level fell into the themes of logistics of accessing care and financial strain. Patients interacted and responded to these challenges by: managing the system, making personal sacrifices, substituting with informal care, and resigning to system constraints. Identifying the barriers patients encounter and the lengths they go to in order to access care highlights areas where policy initiatives can focus to develop appropriate and supportive services that are more person and family-centred.


Navigating and diagnosing cognitive frailty in research and clinical domains.
While physical frailty has been recognized as a clinical entity for some time, the concept of cognitive frailty (CF) is now gaining increasing attention in the geriatrics research community. CF refers to the co-occurrence of physical frailty and cognitive impairment in older adults, which has been suggested as a potential precursor to both dementia and adverse physical outcomes. However, this condition represents a challenge for researchers and clinicians, as there remains a lack of consensus regarding the definition and diagnostic criteria for CF, which has limited its utility. Here, using insights from both the physical frailty literature and cognitive science research, we describe emerging research on CF. We highlight areas of agreement as well as areas of confusion and remaining knowledge gaps, and provide our perspective on fine-tuning the current construct, aiming to stimulate further discussion in this developing field.


Haemorrhoids during pregnancy.
Haemorrhoids are varicose veins of the rectum covered by mucosa at or near the anal canal. They are normally asymptomatic, can occur at any age and affect both males and females. In this review, we address the issue of the approach of the obstetrician to haemorrhoids and their management. Haemorrhoids are common in young women and commoner during pregnancy and the puerperium. Obstetricians and gynaecologists should be familiar with haemorrhoids, a proctological disease, diagnosis and their treatment, but they have little experience regarding the impact of pregnancy on haemorrhoids. The obstetrician must be able to relieve symptoms in patients who are pregnant, or who have just delivered.


Clinicopathologic Features of Fatal Non-Anaplastic Follicular Cell-Derived Thyroid Carcinomas.
The vast majority of thyroid cancers, in particular the non-anaplastic follicular cell-derived thyroid carcinomas (non-ANA FCDC), are considered indolent tumors with very low mortality. Hence, it is crucial to analyze the subgroup of these patients who die of disease (DOD) in order to identify clinicopathologic features predictive of disease-specific mortality. All non-ANA FCDC operated at a tertiary cancer center between 1985 and 2010 who were DOD were identified and submitted to a meticulous clinicopathologic analysis. Out of 3750 non-ANA FCDC, 58 (1.5%) DOD cases were identified. The DOD group was composed of 33 (57%) poorly differentiated carcinomas (PDTC), 14 (24%) tall-cell variant papillary thyroid carcinomas (TCVPTC), four (7%) Hürthle cell carcinomas, three (5%) papillary microcarcinomas, two (3%) classical variant PTC, and two (3%) follicular variant PTC. Twenty-seven (47%) patients presented with distant metastases (DM), 28 (48%) developed DM during follow-up, while the remaining three (5%) had locally advanced non-resectable recurrence. Gross extension beyond the thyroid (GET) was present in 36 (62%) and extensive vascular invasion (VI) in 21 (36%) of cases. All microcarcinomas had PDTC in their clinically apparent cervical lymph nodes at presentation. Encapsulated thyroid carcinomas were responsible for 17% of DOD cases, and all had extensive VI and/or DM at presentation. All patients had at least one of these high-risk features at diagnosis: DM at presentation, PDTC, GET, and/or extensive VI. The majority of patients died from DM (n = 51; 88%), three (5%) from locoregional disease, three (5%) from both, and one (2%) from unknown cause. PDTC and TCVPTC are responsible for the vast majority of deaths in differentiated thyroid carcinomas, while the few fatal classical, follicular variant PTC and microcarcinomas all harbor a PDTC component, DM, or GET. Encapsulated differentiated thyroid carcinoma with focal capsular and/or VI without DM at presentation does not seem to cause death. Lack of DM at presentation, PDTC, GET, and extensive VI identify thyroid carcinomas that are at almost no risk of DOD. The vast majority of patients die of DM rather than locoregional invasion, prompting the need for effective systemic treatment.


Adenoviral-expressed recombinant granulocyte monocyte colony-stimulating factor (GM-CSF) enhances protective immunity induced by inactivated Newcastle Disease Virus (NDV) vaccine.
Although vaccination has been hugely successful in protecting birds against infection by the New castle disease virus (NDV), newly-emerged highly virulent strains have been found to overcome established immune protection and threaten the poultry industry. The need to improve the immunization efficacy is, therefore, urgent. Here, we tested the potential immunostimulatory adjuvant activity of the adenoviral-expressed recombinant chicken granulocyte monocyte colony stimulating factor (rchGM-CSF) in an inactivated Newcastle Disease Virus (NDV) vaccine. 126 commercial layer chicks, divided into six groups, were first vaccinated at day 7, followed by a subsequent boost and later an intramuscular challenge at day 21 and 35 respectively. rchGM-CSF expressed by adenovirus raised NDV-specific hemagglutinin-inhibition (HI) titers from 10 to 12 (log2) and significantly upregulated the production of interferon α/β/γ (IFN-α/β/γ), interleukin-4 (IL-4) and major histocompatibility complex II (MHC-II) in spleens. Crucially, chicks inoculated with the inactivated NDV vaccine plus the rchGM-CSF adjuvant displayed only mild clinical signs, lower tissue viral loads, fewer tissue lesions, and decreased mortality and viral shedding than those in the group immunized with the vaccine alone. Our present work has demonstrated that chicken GM-CSF may act as an enhancer in the orchestration of host immune responses induced by the inactivated NDV vaccine. The molecule, expressed by an adenovirus, has the potential to be used as an immune adjuvant to improve protection by NDV vaccination.


Changes in human skeletal muscle induced by long-term eccentric exercise.
The fine structure of muscle fibres from m. vastus lateralis of nine healthy males (mean age 26 years) was investigated. Four individuals constituted non-exercised controls while five subjects participated in a two-months eccentric muscular training program. Specimens from the controls showed a well-preserved, regular myofibrillar band pattern while changes in the myofibrillar architecture were constantly found in specimens taken after the training program. These changes consisted of Z-band alterations, Z-bands being out of register, extra sarcomeres, Z-band extensions and bisected Z-bands. Between the separated Z-band halves, thin and thick myofilaments as well as abundant glycogen particles and/or ribosomes, were observed. Type-2 (fast-twitch) fibres were predominantly affected. Contrary to the controls the trained individuals constantly showed a greater variation in sarcomere lengths in Type-2 fibres than in Type-1 fibres. It is concluded that muscular work of high tension can induce fine-structural alterations. When repeated over a long period of time, extreme tension demands seem to initiate reorganization in the muscle fibres, predominantly in the, ultrastructurally defined, Type-2 fibres. This adaptation probably results in a better stretchability of the muscle fibres, reduces the risk for mechanical damage and brings about an optimal overlap between actin and myosin filaments.


Fruit removal increases root-zone respiration in cucumber.
Many attempts have been made to avoid the commonly observed fluctuations in fruit initiation and fruit growth in crop plants, particularly in cucumber (Cucumis sativus). Weak sinks of the fruit have been assumed to result in low sink/source ratios for carbohydrates, which may inhibit photosynthesis. This study focuses on the effects of low sink-source ratios on photosynthesis and respiration, and in particular root-zone respiration. Mature fruit-bearing cucumber plants were grown in an aerated nutrient solution. The root containers were designed as open chambers to allow measurement of CO2 gas exchange in the root zone. A similar arrangement in a gas-exchange cuvette enabled simultaneous measurements of CO2 exchange in the shoot and root zones. Reducing the sinks for carbohydrates by removing all fruit from the plants always resulted in a doubling of CO2 exchange in the root zone within a few hours. However, respiration of the shoot remained unaffected and photosynthesis was only marginally reduced, if at all. The results suggest that the increased level of CO2 gas exchange in the root zone after removing the carbon sinks in the shoot is due primarily to the exudation of organic compounds by the roots and their decomposition by micro-organisms. This hypothesis must be tested in further experiments, but if proved correct it would make sense to include carbon leakage by root exudation in cucumber production models. In contrast, inhibition of photosynthesis was measurable only at zero fruit load, a situation that does not occur in cucumber production systems, and models that estimate production can therefore ignore (end-product) inhibition of photosynthesis.


Immunoelectron microscopic localization of the core protein of decorin near the d and e bands of tendon collagen fibrils by use of monoclonal antibodies.
Two monoclonal antibodies, 6D6 and 7B1, previously shown to recognize different epitopes on different regions of the protein core of decorin were used to localize the protein core in relation to the positively stained bands in the D period of bovine tendon collagen fibrils. Peroxidase-antiperoxidase staining revealed that the antigen is associated with the surface of all fibrils and suggested that the axial distance between antigens is D-periodic. Immunoferritin labeling with each antibody produced a distribution of ferritin particles that showed that both epitopes of the protein core are localized near the d and e bands in the D period. The data indicate that the decorin protein core binding site(s) on tendon collagen fibrils is/are located near these bands, axially, within the D period.


[Retrieval of the Optical Thickness and Cloud Top Height of Cirrus Clouds Based on AIRS IR High Spectral Resolution Data].
A study was carried out to retrieve optical thickness and cloud top height of cirrus clouds from the Atmospheric Infrared Sounder (AIRS) high spectral resolution data in 1070~1135 cm-1 IR band using a Combined Atmospheric Radiative Transfer model (CART) by brightness temperature difference between model simulation and AIRS observation. The research is based on AIRS LIB high spectral infrared observation data combined with Moderate Resolution Imaging Spectroradiometer (MODIS) cloud product data. Brightness temperature spectra based, on the retrieved cirrus optical thickness and cloud top height were simulated and compared with brightness temperature spectra of AIRS observation in the 650~1150 cm-1 band. The cirrus optical thickness and cloud top height retrieved were compared with brightness temperature of AIRS for channel 760 (900.56 cm-1, 11. 1 µm) and cirrus reflectance of MODIS cloud product. And cloud top height retrieved was compared with cloud top height from MODIS. Results show that the brightness temperature spectra simulated were basically consistent with AIRS observation under the condition of retrieval in the 650~1150 cm-1 band. It means that CART can be used to simulate AIRS brightness temperature spectra. The retrieved cirrus parameters are consistent with brightness temperature of AIRS for channel 11. 1 µm with low brightness temperature corresponding to large cirrus optical thickness and high cloud top height. And the retrieved cirrus parameters are consistent with cirrus reflectance of MODIS cloud product with high cirrus reflectance corresponding to large cirrus optical thickness and high cloud top height. Correlation coefficient of brightness temperature between retrieved cloud top height and MODIS cloud top height was relatively high. They are mostly located in the range of 8. 5~11.5 km, and their probability distribution trend is approximately identical. CART model is feasible to retrieve cirrus properties, and the retrieval is reliable.


[Monoclonal antibodies as an immunotherapy of rheumatoid arthritis].
Rheumatoid arthritis(RA) is a chronic, deforming and destructive arthritis of unknown etiology. For the medical treatment of RA, NSAID has been the first choice of drug. Recently it has been known that early use of DMARD may result in clinical remission. Understanding of the pivotal role of cytokines and adhesion molecules for the rheumatoid joint destruction enabled us to target these cytokines and molecules as therapeutic measures. Monoclonal antibodies were produced against the cytokines and adhesion molecules such as IL-1, IL-6, IL-6R, TNF-alpha, as well as CD4 molecules. Clinical use of these monoclonal antibodies was found to be effective for rheumatoid arthritis. However these therapeutic measures have several disadvantages such as transient efficacy and side effect.


Comparison of the Unified Parkinson's Disease Rating Scale and the Short Parkinson's Evaluation Scale in patients with Parkinson's disease after levodopa loading.
The Short Parkinson's Evaluation Scale has been compiled and validated previously (Clinical Neuropharmacology, 1997). In the present study, we have assessed and compared the motor scoring of the Unified Parkinson's Disease Rating Scale and the Short Parkinson's Evaluation Scale in 23 patients (mean age, 61.8 years) with Parkinson's disease. Patients were 12 hours off medication at the beginning of the series. They were then given levodopa, 125 mg and 250 mg, on different days and were evaluated each 30 minutes for 2 hours. In addition, patients' motor skills (finger tapping and walking velocity) were measured at each time. Analysis of variance with repeated measures was applied. The results presented show that both scales have the same ability to measure levodopa-dose effect within time. In addition, Spearman's correlation coefficients showed a negative correlation between finger tapping and upper-limb impairment and a positive correlation between walking velocity and lower-limb impairment in both scales. In summary, the present results suggest that Short Parkinson's Evaluation Scale is a useful tool in assessing the effect of medication, having the advantage of being easier and quicker.


Condom use within marital and cohabiting partnerships in KwaZulu-Natal, South Africa.
Traditionally, the major focus of condom-promotion strategies has been on increasing use outside marriage. This study explores the extent and determinants of condom use within marital and cohabiting partnerships in KwaZulu-Natal, South Africa. In focus-group discussions, in-depth interviews, and individual survey responses, knowledge of condoms as an effective method of dual protection against the risk of pregnancy and disease was found to be high. Consistent with numerous other studies, this study found widespread disapproval of condom use within marriage. Only 14 percent of men and 17 percent of women reported consistent or "occasional" condom use. Nevertheless, condom use is much higher among urban, more-educated individuals than among their rural, less-educated counterparts. Apart from education, perceived risk of HIV infection from the partner is the most powerful determinant of use within marital and cohabiting partnerships, particularly for women. Resistance to condoms within marital and cohabiting partnerships is not immutable, however, and women may not be as powerless to protect themselves as is often reported.


Soybean ultrasound pre-treatment prior to soaking affects β-glucosidase activity, isoflavone profile and soaking time.
Ultrasound may convert conjugated isoflavones into their corresponding aglycones, the best form for absorption in the human body. However, ultrasound may also influence the activity of endogenous β-glucosidase. Therefore, the present work evaluated the effects of soybean ultrasound pre-treatment by applying the Box-Behnken design prior to soaking, a step that is important for industries to prepare certain soy products. Furthermore, a multi-response optimisation is provided. The best conditions for soybean ultrasound pre-treatment were established as temperature, X1 = 55 °C; exposure time, X2 = 5 min and ultrasound intensity, X3 = 19.5 W cm-2. Under these conditions, soybeans with higher contents of aglycones were obtained and β-glucosidase activity was kept as high as possible. A second experiment was conducted and confirmed that ultrasound pre-treatment results in a lower soaking time (2 h) to achieve the highest moisture content, lower hardness as well as increased content of aglycones.


Endometriosis and the subsequent risk of epithelial ovarian cancer.
There is a possible correlation between endometriosis and an increased risk of epithelial ovarian cancer (EOC), but many uncertainties remain, including race, exposure or surveillance time, and surgical confirmation. Therefore, we carried out a large-scale, nationwide, controlled cohort study in the Taiwanese women to respond to these uncertainties. A historical cohort study was performed by linking the National Health Insurance Research Database of Taiwan. Each patient diagnosed with endometriosis (n = 7537) between 2000 and 2009 was background matched with up to two women without endometriosis (n = 15,074). The total was 136,643 person-years of follow-up and 24 women having new EOC. Cox regression analysis was used to determine the relationship between the EOC incidence rate and an endometriosis status. The EOC incidence rate of the endometriosis and non-endometriosis women was 3.31 per 10,000 person-years and 0.99 per 10,000 person-years, respectively, contributing to an adjusted hazard ratio (HR) of 3.28 (95% confidence interval, 1.37-7.85). The women with surgical confirmation had a much higher adjusted HR (3.87; 95% confidence interval, 1.58-9.47). No significantly statistical difference of surveillance time between women with and without endometriosis (3.87 years vs. 3.73 years). The occurrence of EOC was not also affected by exposure time of women with endometriosis. Taiwanese women with endometriosis really had a risk of newly developed EOC, especially those who had a surgical diagnosis, and this three-fold increase of risk was neither influenced by exposure time nor biased by surveillance.


Impact of Age on Pain Perception for Typical Painful Diagnoses in the Emergency Department.
Age-related differences in pain perception have been demonstrated in experimental settings but have been investigated scarcely and without valid scale in the clinical framework. To examine the effect of age on pain perception for recognized painful diagnoses encountered in the emergency department (ED). A post-hoc analysis of real-time archived data was performed in a tertiary urban and a secondary regional ED. We included all consecutive adult patients (≥18 years) with the following diagnosis at discharge: renal colic, pancreatitis, appendicitis, headache/migraine, dislocation and extremities fractures, and a pain evaluation of ≥1 (0-10, verbal numerical scale) at triage. The primary outcome was to compare for each of these diagnoses the level of pain intensity between four age groups (18-44; 45-64; 65-74; 75+ years). A total of 15,670 patients (48% women) were triaged with a mean pain intensity of 7.7 (SD=2.0). Women exhibited greater pain scores than men for pancreatitis, headache/migraine, and extremity fracture. Renal colic, pancreatitis, appendicitis, and headache/migraine showed a linear decrease in pain scores with age whereas dislocation and extremity fractures did not present age differences. Mean differences in pain intensity scores between young adults (18-44 years) and patients aged ≥75 years were 0.79 (95% confidence interval [95% CI] 0.5-1.1) for renal colic, 1.1 (95% CI 0.7-1.4) for pancreatitis, 0.70 (95% CI 0.2-1.2) for appendicitis, and 0.86 (95% CI 0.6-1.1) for headache/migraine. Older patients perceive similar pain for dislocation and extremity fractures and less for visceral and headache/migraine pain; however, these age differences may not be clinically important.


High-frequency oscillatory ventilation compared with conventional intermittent mechanical ventilation in the treatment of respiratory failure in preterm infants: neurodevelopmental status at 16 to 24 months of postterm age. The HIFI Study Group.
The High-Frequency Intervention Trial was a 10-center randomized clinical trial to test the efficacy and safety of high-frequency oscillatory ventilation (HFO) in the treatment of neonates weighing 750 to 2000 gm; 327 infants were assigned to HFO and 346 to conventional intermittent mechanical ventilation (IMV). Survival and lung morbidity rates were the same in the two groups. Bayley psychometric evaluations and CNS examination were performed at 16 to 24 months of postterm age in 77% of the survivors (185 HFO and 201 IMV). There was no difference in growth or respiratory status at follow-up. Cerebral palsy was diagnosed in 19 (10%) HFO-treated infants and 23 (11%) IMV-treated infants. There was no difference in severity between the two groups. A significantly higher incidence of hydrocephalus (12% vs 6%) was present in the HFO group (p less than 0.05). Bayley index scores greater than 83 were scored in 57% of HFO-treated infants compared with 66% of IMV-treated infants. The proportion of children at follow-up with a normal neuro-developmental status (i.e., Bayley score greater than 83 and no major CNS defect) was significantly less in the HFO than in the IMV group (54 vs 65%; p less than 0.05). Both treatment groups showed a strong association between the presence of grade 3 or 4 intraventricular hemorrhage and the development of major CNS or cognitive defects. No significant long-term beneficial or deleterious effects were demonstrated in the use of HFO versus IMV for the treatment of respiratory failure in low birth weight premature infants, except that there were slightly more neurologic deficits in the HFO group related to the higher proportion of survivors with major intraventricular hemorrhage.


Extracellular ATP is a danger signal activating P2X7 receptor in a LPS mediated inflammation (ARDS/ALI).
Acute respiratory distress syndrome (ARDS) is a life-threating lung condition resulting from a direct and indirect injury to the lungs [1, 2]. Pathophysiologically it is characterized by an acute alveolar damage, an increased permeability of the microvascular-barrier, leading to protein-rich pulmonary edema and subsequent impairment of arterial oxygenation and respiratory failure [1]. This study examined the role of extracellular ATP in recruiting inflammatory cells to the lung after induction of acute lung injury with lipopolysaccharide (LPS). However, the precise mechanism is poorly understood. Our objective was to investigate the functional role of the P2X7 receptor in the pathogenesis of acute respiratory distress syndrome (ARDS/ acute lung injury (ALI)) in vitro and in vivo. We show that intratracheally applied LPS causes an acute accumulation of ATP in the BALF (bronchoalveolar lavage) and lungs of mice. Prophylactic and therapeutic inhibition of P2X7R signalling by a specific antagonist and knock-out experiments was able to ameliorate the inflammatory response demonstrated by reduced ATP-levels, number of neutrophils and concentration of pro-inflammatory cytokine levels in the BALF. Experiments with chimeric mice showed that P2X7R expression on immune cells was responsible for the observed effect. Consistently, the inflammatory response is diminished only by a cell-type specific knockdown of P2X7 receptor on non-stationary immune cells. Since the results of BALF from patients with acute ARDS or pneumonia simulated the in vivo data after LPS exposure, the P2X7 receptor may be a new therapeutic target for treatment in acute respiratory distress syndrome (ARDS/ALI).


Correlation of laboratory and clinical criteria in the prediction of postcesarean endomyometritis.
The objective of this investigation was to develop a rapid diagnostic test to identify patients at exceptionally high risk for postcesarean endomyometritis. Intraoperative samples of endometrium, chorioamniotic membrane, and amniotic fluid were obtained from 70 patients undergoing nonelective cesarean section and were processed for bacterial culture, Gram stain, and histologic examination. Endomyometritis occurred in 57% of patients. Women with positive bacterial cultures (growth of high virulence organisms on the primary plates), positive Gram stains (bacteria in any oil immersion field), and histologic evidence of leukocytic infiltration in the chorioamniotic membrane and endometrium (greater than or equal to ten white blood cells per high-power field) were more likely than were patients with negative findings to develop endomyometritis. All of the laboratory tests evaluated were specific but insensitive predictors of infection. Assessment of duration of ruptured membranes and length of labor provided a diagnostic test that was as clinically useful in predicting postoperative infection as were any of the laboratory studies evaluated.


[The cryopreservation technology in research and development of tissue engineered products].
In this brief review, some key issues related to cryopreservation of seeding cells, scaffolds, and engineered tissues are outlined. The importance of cryopreservation technology to the research and development of tissue engineered products is demonstrated. The biological or biochemical reaction rate must be reduced or completely shut off in order to preserve the tissue engineered products for a long period of time. Cryopreservation may be one of the possible approaches to the fulfillment of this requirement. Seeding cells are stored at low temperature. Tissue engineered scaffold products are usually lyophilized. Engineered tissues are preserved by vitreous cryopreservation technology.


Proteome Analysis of Human Perilymph Using an Intraoperative Sampling Method.
The knowledge about the etiology and pathophysiology of sensorineural hearing loss (SNHL) is still very limited. This study aims at the improvement of understanding different types of SNHL by proteome analysis of human perilymph. Sampling of perilymph was established during inner ear surgeries (cochlear implantation, vestibular schwannoma surgeries), and safety of the sampling method was determined by checking hearing threshold with pure-tone audiometry postoperatively. An in-depth shot-gun proteomics approach was performed to identify cochlear proteins and the individual proteome in perilymph of patients. This method enables the identification and quantification of protein composition of perilymph. The proteome of 41 collected perilymph samples with volumes of 1-12 μL was analyzed by data-dependent acquisition, resulting in overall 878 detected protein groups. At least 203 protein groups were solely identified in perilymph, not in reference samples (serum, cerebrospinal fluid), displaying a specific protein pattern for perilymph. Samples were grouped by patient's age and surgery type, leading to the identification of some proteins specific to particular subgroups. Proteins with different abundances between different sample groups were subjected to classification by gene ontology annotations. The identified proteins might serve as biomarkers to develop tools for noninvasive inner ear diagnostics and to elucidate molecular profiles of SNHL.


Structure-Activity Study of Ghrelin(1-8) Resulting in High Affinity Fluorine-Bearing Ligands for the Ghrelin Receptor.
The ghrelin receptor, also known as the growth hormone secretagogue receptor 1a (GHS-R1a), is a G-protein-coupled receptor that is differentially expressed in healthy tissue and several cancers, including prostate, testicular, and ovarian. Selectively targeting the ghrelin receptor using fluorine-18 tagged entities would allow localization and visualization of ghrelin receptor expressing carcinomas using PET imaging. The endogenous ligand ghrelin, a 28 amino acid peptide with 3.1 nM affinity, has poor in vivo stability. Here we report on ghrelin(1-8) analogues bearing modifications at residues 1, 3, 4, and 8. The lead analogue, [Inp1,Dpr3(6-fluoro-2-naphthoate),1-Nal4,Thr8]ghrelin(1-8), possessed an IC50 value of 0.11 nM that is a 28-fold improvement compared to the natural ligand. A novel 6-fluoro-2-pentafluorophenyl naphthoate (PFPN) prosthetic group was synthesized to incorporate fluorine-18 for PET imaging. This is not only the highest affinity ghrelin analogue reported but also the shortest ghrelin analogue capable of binding GHS-R1a with better affinity than ghrelin(1-28).


[Dilated cardiomyopathy: role of clinical and laboratory evaluation].
From the clinical standpoint a cardiomyopathy can be classified as primitive when other causes, i.e. ischemic, infiltrative, systemic diseases, can be ruled out. Initial symptoms usually include a progressive dyspnea and fatigue with tachycardia in a patient previously healthy. Congestive heart failure may be the initial manifestation. Angina is often present, not only because of coronary heart disease. Auscultatory findings usually include a gallop rhythm with a third heart sound, not rarely a four-sound gallop. Blood test to evaluate renal and liver function should be performed. The dosage of troponin I and/or troponin T, plasma renin activity, brain natriuretic peptide or endothelins has recently gained some reputation to indicate prognosis, but there is no reason to believe that these measures are superior to cardiopulmonary stress test.


Effects of cigarette smoke on the immune system.
Although the health risks of tobacco smoking are well documented, there is increasing evidence that smokers have a lower incidence of some inflammatory and neurodegenerative diseases. Many of the adverse and beneficial effects of smoking might result from the ability of cigarette smoke to suppress the immune system. Nicotine, which is one of the main constituents of cigarette smoke, suppresses the immune system but might have therapeutic potential as a neuroprotective and anti-inflammatory agent.


IgG4-related autoimmune pancreatitis involving the colonic mucosa.
We report a case of autoimmune pancreatitis involving the colonic mucosa. Although serum level of IgG4 was normal, computed tomography and endoscopic retrograde cholangiopancreatography showed diffuse enlargement of the pancreas and irregular narrowing of the pancreatic ducts, respectively. Colonoscopy revealed a polypoidal lesion in the ascending colon. A lymphoplasmacytic infiltration was seen both in the pancreas and in the polypoidal lesion of the colon. Furthermore, immunohistochemical analysis showed abundant IgG4-positive plasma cells in these lesions. This is the first case report of a simultaneous occurrence of autoimmune pancreatitis and a colonic polypoidal lesion, both of which are characterized with increased IgG4 responses.


A review of signal processing used in the implementation of the pulse oximetry photoplethysmographic fluid responsiveness parameter.
ΔPOP is a physiological parameter derived from the respiration-induced change in the pulse oximetry plethysmographic (POP) waveform or "pleth." It has been proposed as a proxy for pulse pressure variation used in the determination of the response to intravascular volume expansion in hypovolemic patients. Many studies have now reported on the parameter, and many research groups have constructed algorithms for its computation from the first principles where the implementation details have been described. This review focuses on the signal processing aspects of ΔPOP, as reported in the literature, and aims to provide a comprehensive summary of the wide-ranging algorithmic strategies that have been attempted in its computation. A search was conducted for articles concerning the use of ΔPOP as a fluid responsiveness parameter. In particular, articles concerning the correlation between ΔPOP and pulse pressure variation were targeted. Comments and replies to comments by the authors in which signal processing aspects were discussed were also included in the review. The parameter is first defined, and a history of the early work surrounding pleth-based fluid responsiveness parameters is presented. This is followed by an overview of the signal processing methods used in the reported studies, including details of exclusion criteria, manual filtering (preprocessing), gain change issues, acquisition details, selection of registration periods, averaging methods, physiological influences on the pleth, and comments by the investigators themselves. It is concluded that to develop a robust, fully automated ΔPOP algorithm for use in the clinical environment, more rigorous signal processing is required. Specifically, signals should be evaluated over significant periods of time, with emphasis on the quality and temporal relevance of the information.


MicroRNA-375 regulation of thymic stromal lymphopoietin by diesel exhaust particles and ambient particulate matter in human bronchial epithelial cells.
Air pollution contributes to acute exacerbations of asthma and the development of asthma in children and adults. Airway epithelial cells interface innate and adaptive immune responses, and have been proposed to regulate much of the response to pollutants. Thymic stromal lymphopoietin (TSLP) is a pivotal cytokine linking innate and Th2 adaptive immune disorders, and is upregulated by environmental pollutants, including ambient particulate matter (PM) and diesel exhaust particles (DEP). We show that DEP and ambient fine PM upregulate TSLP mRNA and human microRNA (hsa-miR)-375 in primary human bronchial epithelial cells (pHBEC). Moreover, transfection of pHBEC with anti-hsa-miR-375 reduced TSLP mRNA in DEP but not TNF-α-treated cells. In silico pathway evaluation suggested the aryl hydrocarbon receptor (AhR) as one possible target of miR-375. DEP and ambient fine PM (3 μg/cm(2)) downregulated AhR mRNA. Transfection of mimic-hsa-miR-375 resulted in a small downregulation of AhR mRNA compared with resting AhR mRNA. AhR mRNA was increased in pHBEC treated with DEP after transfection with anti-hsa-miR-375. Our data show that two pollutants, DEP and ambient PM, upregulate TSLP in human bronchial epithelial cells by a mechanism that includes hsa-miR-375 with complex regulatory effects on AhR mRNA. The absence of this pathway in TNF-α-treated cells suggests multiple regulatory pathways for TSLP expression in these cells.


Identification of fluorescent beads using a coded aperture snapshot spectral imager.
We apply a coded aperture snapshot spectral imager (CASSI) to fluorescence microscopy. CASSI records a two-dimensional (2D) spectrally filtered projection of a three-dimensional (3D) spectral data cube. We minimize a convex quadratic function with total variation (TV) constraints for data cube estimation from the 2D snapshot. We adapt the TV minimization algorithm for direct fluorescent bead identification from CASSI measurements by combining a priori knowledge of the spectra associated with each bead type. Our proposed method creates a 2D bead identity image. Simulated fluorescence CASSI measurements are used to evaluate the behavior of the algorithm. We also record real CASSI measurements of a ten bead type fluorescence scene and create a 2D bead identity map. A baseline image from filtered-array imaging system verifies CASSI's 2D bead identity map.


Combined endoscopic and extracorporeal shock-wave treatment in difficult bile duct stones: early and long-term results.
Endoscopic papillosphincterotomy (EPT) has become a well-established therapeutic procedure in the management of common bile duct stones; however, in difficult cases with large stones or anatomic conditions limiting the amplitude of the sphincteric section, the procedure may fail. In these cases, the association with extracorporeal shock-wave lithotripsy (ESWL) has proved to be helpful. Twenty out of 21 patients in whom the endoscopic approach failed because of the presence of large stones in the biliary tree (15 cases) or anatomic conditions (5 cases) underwent ESWL treatment. Stone fragmentation was achieved in 18 of the 20 treated patients (90%), with spontaneous clearing of the fragments in 10 patients after ESWL sessions and in another 2 patients within three months. In 6 cases the residual fragments were extracted by means of endoscopy. The combined procedures were therefore successful in all the 18 cases in which stone fragmentation was obtained. Complications occurred in two cases after ESWL treatment (asymptomatic pancreatic reaction and severe bleeding from the papillary area). Clinical, ultrasound and biochemical evaluations at 6 and 12 months documented a normal condition in all but two treated subjects.


A Retrospective Study of Psychotropic Drug Use and Prescription Opioid Initiation Among Older Adults.
Individuals with mental health problems may be more vulnerable to using prescription opioids than their counterparts. Therefore, the main objective of this study was to assess the initiation of prescription opioids in older adults who used psychotropic drugs compared with those who did not. The authors used a retrospective cohort design and included a sample of older adults enrolled in Pennsylvania's Pharmaceutical Assistance Contract for the Elderly program who did not use prescription opioids in 2013. Using pharmacy claims, patients who used anxiolytics/sedatives/hypnotics (n = 13,512) or antidepressants (n = 17,492) between October and December 2013 were identified and compared with those who did not use anxiolytics/sedatives/hypnotics (n = 114,091) or antidepressants (n = 110,111) during that period, to determine the incidence of prescription opioid use in 2014. Chi-square tests and multivariate logistic regressions were performed for analyses. Compared with patients who did not use anxiolytics/sedatives/hypnotics, those who used were more likely to initiate prescription opioids (15.0% versus 22.0%, P < .0001). Similarly, compared with patients who did not use antidepressants, those who used were more likely to initiate prescription opioids (14.7% versus 21.9%, P < .0001). Multivariate logistic regression indicated that the odds of prescription opioid initiation increased with anxiolytic/sedative/hypnotic use by 44% (AOR = 1.44; P < .0001) and antidepressant use by 48% (AOR = 1.48; P < .0001) among older adults after adjusting for potential confounding variables. Results showed that prescription opioid initiation is associated with prior anxiolytic/sedative/hypnotic or antidepressant use among older adults. Patients with mental health problems should also be queried about pain experiences for effective treatment.


Wild-type Yellow fever virus in cerebrospinal fluid from fatal cases in Brazil, 2018.
Yellow fever virus (YFV) is the causative agent of yellow fever (YF), a hemorrhagic and viscerotropic acute disease. Severe YF has been described in approximately 15-25% of YF patients, with 20-50% of severe YF cases being fatal. Here we analyzed cerebrospinal fluid (CSF) samples collected during the YF outbreak in Brazil in 2018, aiming to investigate CNS neuroinvasion in fatal YFV cases. YFV RNA was screened by RT-qPCR targeting the 3'UTR region of the YFV genome in CSF. CSF samples were tested for the presence of anti-YFV IgM and neutralizing antibodies, coupled with routine laboratory examinations. Among the 13 patients studied, we detected anti-YFV IgM in CSF from eight patients and YFV RNA in CSF from five patients. YFV RNA genomic load in CSF samples ranged from 1.75×103 to 5.42×103 RNA copies/mL. We genotyped YFV from three CSF samples that grouped with other YFV samples from the 2018 outbreak in Brazil within the South-American I genotype. Even though descriptions of neurologic manifestations due to wild type YFV (WT-YFV) infection are rare, since the last YF outbreak in Brazil in 2017-2018, a few studies have demonstrated WT-YFV RNA in CSF samples from YF fatal cases. Serological tests indicated the presence of IgM and neutralizing antibodies against YFV in CSF samples from two patients. Although the presence of viral RNA, IgM and neutralizing antibodies in CSF samples could indicate neuroinvasiveness, further studies are needed to better elucidate the role of YFV neuroinvasion and possible impacts in disease pathogenesis.


Current management strategy of nasopharyngeal carcinoma.
Nasopharyngeal carcinoma is an unique head and neck cancer. It is common among the southern Chinese and is closely associated with the Epstein Barr virus (EBV). To diagnose the disease in its early stage is infrequent as the symptoms are usually trivial and patients only present in late stages. Testing the blood for elevated EBV DNA has now become a screening test for the high risk group of patients, aiming to diagnose the disease in its early stages. Imaging studies, positron emission tomography scans in addition to clinical examination provide information on the extent of the disease. The confirmation of the disease still depends on endoscopic examination and biopsy. Radiotherapy with or without chemotherapy has been the primary treatment modality. The application of intensity modulated radiotherapy and the use of concomitant chemoradiation have improved the control of nasopharyngeal carcinoma together with the reduction of long term side effects. The early detection of residual or recurrence tumor in the neck or at the primary site has allowed delivery of salvage treatment. The choice of the optimal surgical salvage, either for neck disease or primary tumor depends on the extent of the residual or recurrent disease. The outcome of these patients have improved with the application of the appropriate surgical salvage.


Temperature-dependent magnetotransport around ν=1/2 in ZnO heterostructures.
The sequence of prominent fractional quantum Hall states up to ν=5/11 around ν=1/2 in a high-mobility two-dimensional electron system confined at oxide heterointerface (ZnO) is analyzed in terms of the composite fermion model. The temperature dependence of R(xx) oscillations around ν=1/2 yields an estimation of the composite fermion effective mass, which increases linearly with the magnetic field. This mass is of similar value to an enhanced electron effective mass, which in itself arises from strong electron interaction. The energy gaps of fractional states and the temperature dependence of R(xx) at ν=1/2 point to large residual interactions between composite fermions.


Surface modification of aramid fibers by bio-inspired poly(dopamine) and epoxy functionalized silane grafting.
A novel biomimetic surface modification method for meta-aramid (MPIA) fibers and the improvement on adhesion with rubber matrix was demonstrated. Inspired by the composition of adhesive proteins in mussels, we used dopamine (DOPA) self-polymerization to form thin, surface-adherent poly(dopamine) (PDA) films onto the surface of MPIA fibers simply by immersing MPIA fibers in a dopamine solution at room temperature. An epoxy functionalized silane (KH560) grafting was then carried out on the surface of the poly(dopamine)-coated MPIA, either by a "one-step" or "two-step" method, to introduce an epoxy group onto the MPIA fiber surface. The surface composition and microstructure of the modified MPIA was characterized by X-ray photoelectron spectroscopy (XPS), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). The results indicated successful grafting of KH560 on the PDA-coated MPIA surface. A single-fiber pull-out test was applied to evaluate the adhesion of MPIA fibers with the rubber matrix. Compared with the untreated MPIA fibers, the adhesion strength between the modified MPIA fibers by "one step" method with rubber matrix has an increase of 62.5%.


Comparison of Patients' and Doctors' Reports on Health-related Quality of Life in Celiac Disease.
To investigate whether implementation of a celiac disease (CD)-specific health-related quality of life (HRQOL) questionnaire would add value to CD follow-up visits; we compared patients' self-reported CD-specific HRQOL with the physician's report provided during a regular CD follow-up visit in children and young adults. A cross-sectional study in the control group of a study on self-management in CD (CoelKids). Eligible patients had CD for ≥1 year and were 25 years or younger. They completed a CD-specific HRQOL questionnaire (CDDUX) after their regular follow-up visit. Their physicians were unaware of the present study's objectives or self-reported HRQOL. agreement between physician-reported and self-reported HRQOL. patient variables predicting a discrepancy between reports, or a lower HRQOL. Physician-reported HRQOL was available in 70 of 78 enrolled patients. The self-reported and physician-reported HRQOL were concordant in 30 of 70 (K = 0.093), 6 of them had a poor self-reported HRQOL. Reports were discrepant in 40 of 70; all 40 self-reported a poor HRQOL. Discrepancies occurred more frequently in patients with a disease duration <9 years (32/40 with discrepant reports were diagnosed <9 years ago vs 17/30 with no discrepancy, P<0.001) and in females (35/40 with discrepant reports were girls versus 16 of 30 with no discrepancy, P = 0.001). Both factors were predictors of a poorer HRQOL. During regular CD follow-up visits, physicians did not report a poor HRQOL in 40 of 46 children and young adults with a poor self-reported HRQOL. This is consistent with previous studies examining other chronic diseases and supports the implementation of self-reported CD-specific HRQOL measurements in CD follow-up visits.


A double-blind placebo-controlled trial of perioperative prophylactic antibiotics for elective neurosurgery.
In this study, 417 patients undergoing "clean" elective neurosurgical operative procedures were randomized to receive a broad-spectrum antibiotic (piperacillin) or placebo given as three perioperative doses, each 6 hours apart. Randomization was carried out by hospital pharmacists, and the investigators remained blinded until the end of the study. Twenty cases were excluded from analysis because either an unforeseen second operation was performed or antibiotic therapy was initiated within 30 days after surgery to treat infection or the risk of infection. Twelve of the 205 patients treated with placebo developed postoperative wound sepsis, and four of the 192 piperacillin-treated patients developed wound sepsis--a statistically significant difference (p less than 0.05, Fisher's exact test). Piperacillin thus appeared to reduce the incidence of neurosurgical wound infection in this study.


Ischaemic stroke as the initial manifestation of systemic amyloidosis.
A previously healthy 54-year-old woman was admitted to the stroke unit with an acute ischaemic stroke attributed to atrial fibrillation newly diagnosed at the emergency room. Nevertheless, preliminary investigation on stroke aetiology revealed incidental hypoalbuminaemia in the context of nephrotic syndrome, while clinically, the patient developed progressive signs of cardiac failure raising the suspicion of an underlying disorder. Systemic amyloidosis was histologically confirmed a few weeks after hospital admission. The rare presentation and non-specific symptom constellation contributed to delayed institution of the appropriated treatment regimen at a point where multiorganic involvement was irreversible leading to death only 2 months after the first manifestation. The presented case reminds us of the importance of always keeping in mind this rarer cause of ischaemic stroke since an early diagnosis remains the key to a more hopeful prognosis.


Population genetics of Great Basin feral horses.
The genetic make-up of Great Basin wild (feral) horses was investigated by blood typing studies. Blood samples of 975 feral horses from seven trap sites in Nevada and Oregon were tested by serological and electrophoretic techniques for genetic markers at 19 polymorphic loci. The average number of variants for the seven feral populations [72.1 +/- 3.2 (SEM), range 62-85] was not significantly different from that of 16 domestic breeds (75.0 +/- 11.5, range 58-105). The expected average frequency of heterozygotes per locus (average heterozygosity) for the feral populations (0.402 +/- 0.009, range 0.368-0.442) was not significantly different from the domestic breeds (0.389 +/- 0.045, range 0.295-0.443). Dendrograms constructed using pairwise comparisons of Nei's distance measurements substantiated anecdotal accounts of the origins of Great Basin horses from Iberian, American saddle horse and draft horse breeds.


Receptor Activator of Nuclear Factor (Nf)-kb Ligand Promotes T Helper 17 Cell Differentiation through Fas.
T helper 17 (Th17) cells play important role in the defense against pathogens and autoimmune diseases. Many cytokines can induce Th17 cell differentiation. However, the mechanism of Th17 cell differentiation is not well clarified. RankL, a member of the TNF superfamily, binds with Rank and then participates in the proliferation and differentiation of many kinds of cells. Recent studies showed that RankL-Rank signaling is closely related to Th17 differentiation and function. The detail of the Rank-RankL pathway in Th17 cell differentiation is still unclear. To illustrate the role of Rank-RankL in Th17 differentiation, naive CD4 + T cells were differentiated into Th17 cells with or without RankL stimulation. During Th17 differentiation, the expression of Rank obviously increased. The RankL stimulation significantly increased Th17 cell differentiation indicated by increased IL-17-positive cell number, highly expressed IL-17 and IL-22 and elevated IL-17 secretion. These effects were canceled by Rank-Fc addition. In further study, RankL treatment during Th17 differentiation up-regulated Fas expression. Fas knockdown inhibited the Th17 differentiation promoted by RankL. In this study, it was confirmed that Rank-RankL signaling could promote Th17 cell differentiation through Fas induction.


A new Afrotropical genus Monocentroptilum gen. n. (Ephemeroptera: Baetidae: Protopatellata).
A new genus Monocentroptilum gen. n. is established for a single Afrotropical species, originally described as Centroptilum badium Kopelke 1980 from Congo. Larvae, subimagoes, imagoes of both sexes and eggs of Monocentroptilum badium comb. n. are described here based on reared material from Uganda.


Clinical Significance and Prognostic Value of Lactate Dehydrogenase Expression in Cervical Cancer.
Background: Lactate dehydrogenase (LDH) is a marker of injury and disease as it is expressed extensively in numerous cell types and tissues. Moreover it is released during tissue breakdown, and is elevated in cancerous tissues. However, the clinical significance and prognostic value of LDH as a tumor marker have been subject to considerable discussion. Objective: In this study, clinical serum LDH data from patients with cervical cancer (CC), CC microarray data, and RNA-seq data were integrated to assess the expression of LDH in CC. Methods: A total of 204 patients with newly diagnosed CC and 204 age-matched healthy controls were included to evaluate serum LDH levels in CC and non-cancer samples. External microarrays and RNA-seq datasets were collected for the differential expression analysis of LDH in CC and non-cancer tissue samples. Kaplan-Meier survival curves of the prognostic value of LDH for CC were plotted for RNA-seq data. Functional enrichment analysis was performed for the genes co-expressed with LDH. Results: The data from our in-house clinical cases as well as the data extracted from microarrays and RNA-seq databases demonstrated significant overexpression of LDH in CC samples. Elevated LDH expression levels were associated with poor overall survival in CC patients. The genes co-expressed with LDH were significantly correlated with the biological processes and pathways, associated with nuclear division, the condensed chromosome, protein serine/threonine kinase activity, and the cell cycle. Conclusion: In conclusion, LDH upregulation might serve as a therapeutic and prognostic biomarker for CC.


Sepsis Mimicker in an Human Immunodeficiency Virus-Infected Patient.
A 22-year-old human immunodeficiency virus-infected male presented with fever, rash, hypotension, and renal insufficiency 18 days following initiation of therapy with an efavirenz-based antiretroviral regimen. Although rash is a common side effect of efavirenz, severe hypersensitivity reactions are rare. Systemic symptoms can include hepatic toxicity and pneumonitis, and in one instance death. Corticosteroids are the mainstay of treatment.


C-LFP-multi-walled carbon nanotubes composite cathode materials synthesized by solid-state reaction for lithium ion batteries.
Multi-walled carbon nanotubes (MWNT) was utilized as a conductive additive to enhance the capacity and rate capability of carbon coated LiFePO4 (C-LFP). Composites of C-LFP with MWNT (C-LFP-MWNT) were prepared by blending MWNT at different stages of C-LFP synthesis. The pre-blending (PrB) of MWNT (5, 10, 15 wt%) with LFP precursor (PrB-C-LFP-MWNT) before calcination in a reducing environment (5 vol% H2 in N2) at 750 degrees C, produced phase pure crystalline LFP with a reduction in particle size as increase in MWNT content. This was contrasted with post-blending (PoB) of MWNT with as-synthesized C-LFP (PoB-C-LFP-MWNT), which gave inferior electrochemical performances. The PrB-C-LFP-MWNT (10 wt%) composite showed better cycle stability, higher rate capability, and faster Li diffusion characteristics than PoB-C-LFP-MWNT.


Spontaneous Rupture of Intracranial Dermoid Cyst Mimicking a Primary Psychiatric Disorder.
We discussed the case of a 14-year-old patient with acute onset of psychiatric symptoms for two months who had been examined and different antipsychotic drugs had been prescribed by several psychiatrists without any neuroradiological imaging. Because of unresponsiveness to the antipsychotic drugs, computed tomography and magnetic resonance imaging were performed which revealed a ruptured intracranial dermoid cyst. The patient underwent surgery and antipsychotic medications were withdrawn in short time. The emphasis of this case is that intracranial lesions can present with neuropsychiatric symptoms and findings only without any neurological deficit or signs.


Genetic relationships of ethnic minorities in Southwest China revealed by microsatellite markers.
Population migrations in Southwest and South China have played an important role in the formation of East Asian populations and led to a high degree of cultural diversity among ethnic minorities living in these areas. To explore the genetic relationships of these ethnic minorities, we systematically surveyed the variation of 10 autosomal STR markers of 1,538 individuals from 30 populations of 25 ethnic minorities, of which the majority were chosen from Southwest China, especially Yunnan Province. With genotyped data of the markers, we constructed phylogenies of these populations with both D(A) and D(C) measures and performed a principal component analysis, as well as a clustering analysis by structure. Results showed that we successfully recovered the genetic structure of analyzed populations formed by historical migrations. Aggregation patterns of these populations accord well with their linguistic affiliations, suggesting that deciphering of genetic relationships does in fact offer clues for study of ethnic differentiation.


The conjugative DNA translocase TrwB is a structure-specific DNA-binding protein.
TrwB is a DNA-dependent ATPase involved in DNA transport during bacterial conjugation. The protein presents structural similarity to hexameric molecular motors such as F(1)-ATPase, FtsK, or ring helicases, suggesting that TrwB also operates as a motor, using energy released from ATP hydrolysis to pump single-stranded DNA through its central channel. In this work, we have carried out an extensive analysis with various DNA substrates to determine the preferred substrate for TrwB. Oligonucleotides with G-rich sequences forming G4 DNA structures were the optimal substrates for TrwB ATPase activity. The protein bound with 100-fold higher affinity to G4 DNA than to single-stranded DNA of the same sequence. Moreover, TrwB formed oligomeric protein complexes only with oligonucleotides presenting such a G-quadruplex DNA structure, consistent with stoichiometry of six TrwB monomers to G4 DNA, as demonstrated by gel filtration chromatography and analytical ultracentrifugation experiments. A protein-DNA complex was also formed with unstructured oligonucleotides, but the molecular mass corresponded to one monomer protein bound to one oligonucleotide molecule. Sequences capable of forming G-quadruplex structures are widespread through genomes and are thought to play a biological function in transcriptional regulation. They form stable structures that can obstruct DNA replication, requiring the action of specific helicases to resolve them. Nevertheless, TrwB displayed no G4 DNA unwinding activity. These observations are discussed in terms of a possible role for TrwB in recognizing G-quadruplex structures as loading sites on the DNA.


Chemophenetics as a Tool for Distinguishing Morphotypes of Annona emarginata (Schltdl.) H. Rainer.
Annona emarginata (Annonaceae) has two morphological variations (A. emarginata 'mirim' and A. emarginata 'terra-fria'). The species has agricultural value and produces specialized metabolites of pharmacological interest. The objective of this work was to analyze whether chemical and morphological differences contribute to differentiate A. emarginata 'terra-fria' from A. emarginata 'mirim', as chemophenetic variations of A. emarginata. The analysis of chemical compounds was based on the quantification, profile of root alkaloids and on the leaves volatile profile, together with morphometric analyses of the leaf blade. The samples were collected in three phenological stages (flowering, fruiting, and vegetative) at two places in São Paulo, Brazil. Differences in the composition of the alkaloid profile and leaf volatiles (in both places and in the three phenological stages) allowed us to separate the two morphotypes by multivariate statistical analysis. These differences agreed with the leaf blade morphology and flower color. This first chemophenetic report of A. emarginata demonstrates that, in addition to morphological variations, the specialized metabolism of roots and leaves can be phytochemical characters, which suggest the existence of at least morphochemotypes of A. emarginata.


Advanced volume holographic filter to improve the SNR of polychromatic sources in a noisy environment.
We present a new type of filter that improves the SNR of systems where polychromatic signal and noise are located at different distances within the same line of sight. The filter is based on holographic technology that allows for the discrimination of wavefronts by range. In using a combination of two holographic elements, a pre-disperser and a thick volume hologram, we were able to significantly increase the spectral bandwidth of the filter, from 9nm without the pre-disperser to 70nm with both holographic elements. Laboratory proof of concept demonstrated that such a filter is capable of an SNR improvement of 15 dB for a monochromatic source, and up to 7.6 dB for a polychromatic source. This filter can find applications in astronomic observation, satellite or space debris tracking, and free-space optical communication.


Isolation and characterization of Clostridium difficile in farm animals from slaughterhouse to retail stage in Isfahan, Iran.
To determine the prevalence of Clostridium difficile in farm animals from slaughterhouse through to retail stage, a total of 750 samples of feces, posteviscerated and washed carcass were collected from cattle, camels, goats, and sheep in Isfahan, Iran. The overall prevalence of C. difficile in feces, posteviscerated and washed carcass were 20 (13.3%), 23 (15.3%), and 11 (7.3%), respectively; while C. difficile was isolated from 79 (26.3%) retail samples. Twenty-nine (3.8%) isolates were toxigenic, with most toxigenic isolates (n = 17, 5.6%) identified from the retail stage. All toxigenic isolates harbored tcdA and tcdB; however, all were negative for cdtB. The 29 isolates were classified into 21 different ribotypes. This study revealed evidence of existence of toxigenic C. difficile in farm animal feces and meat in Iran.


Chronic renal failure in a boy with classic Bartter's syndrome due to a novel mutation in CLCNKB coding for the chloride channel.
Progressive renal failure in patients with classic Bartter's syndrome (cBS) due to inactivating mutations in CLCNKB gene is extraordinarily rare. We describe a 17-year-old Chinese boy who presented with progressive muscle weakness and renal failure. He was diagnosed as BS of unknown type at the age of 9 months and treated with indomethacin (2 mg/kg/day) and potassium chloride (KCl) supplementation (1.5 mEq/kg/day) for hypokalemia (2.5 mmol/l). At the age of 12 years, serum K+ was 3.0 mmol/l and creatinine reached 2.0 mg/dl. On admission, his blood pressure was normal but volume status was depleted. Urinalysis was essentially normal. Biochemical studies showed hypokalemia (K+ 2.4 mmol/l) with a high transtubular K+ gradient (TTKG) 9.6, metabolic alkalosis (HCO3- 28.4 mmol/l), normomagnesemia (2.0 mg/dl), severe renal failure (BUN 94 mg/dl, Cr 6.3 mg/dl), and hypocalciuria (urine calcium/creatinine ratio 0.02 mg/mg). Abdominal sonography revealed bilateral small size kidneys without nephrocalcinosis or renal stones. After the withdrawal of indomethacin with regular KCl and adequate fluid supplementation for 1 year, serum creatinine and K+ levels have been maintained at 4.0 mg/dl and 3.3 mmol/l, respectively. Direct sequencing of NKCC2, ROMK, ClC-Kb, and NCCT in this patient disclosed a novel homozygous missense mutation (GGG to GAG, G470E) in CLCNKB. This G470E mutation was not identified in 100 healthy Chinese subjects. Long-term therapy of non-steroidal anti-inflammatory drugs (NSAIDs), prolonged hypokalemia, chronic volume depletion, and underlying genetic variety may contribute to the deterioration of his renal function. The cautious use of NSAIDs, aggressive correction of hypokalemia, and avoidance of severe volume depletion may prevent the irreversible renal damage in patients with BS due to a Cl- channel defect.


Suppression of human anti-inflammatory plasma cytokines IL-10 and IL-1RA with elevation of proinflammatory cytokine IFN-gamma during the isolation of the Antarctic winter.
Cellular immune function has been shown to be decreased and latent virus shedding to be increased in human beings isolated during the Antarctic winter, a model used for assessing some effects of space flight. However, the balance of proinflammatory (IFN-gamma) and anti-inflammatory (IL-10 and IL-1RA) cytokines has not previously been evaluated. We therefore sought to determine whether isolation during the Antarctic winter would alter the proinflammatory and anti-inflammatory cytokine balance. Cytokine levels were measured with ELISA in monthly plasma samples from January through September 1999 in 21 study subjects in the Antarctic and 7 control subjects on Macquarie Island. There was a significant time-dependent increase in plasma IFN-gamma (P =.039) as well as decreases in IL-10 (P =.042) and IL-1RA (P =.053) in the study subjects compared with the control subjects. The study subjects also had significantly increased plasma IFN-gamma levels (P < or =.045) but decreased IL-10 and IL-1RA levels (P < or =.036) at individual time points of isolation. Isolation of human beings in the Antarctic appears to shift the plasma cytokine balance toward a proinflammatory profile. These observations are consistent with T-cell activation that might be due to activation of latent viruses, and they could hold importance for determining the risks of space flight.


Protective effect of Teucrium polium on carbon tetrachloride induced genotoxicity and oxidative stress in rats.
This study aimed to investigate the protective effects of Teucrium polium (TP) on carbon tetrachloride (CCl4) induced spleen, erythrocyte's oxidative stress, and genotoxicity in rats. TP was found to contain large amounts of polyphenols (150 mg GAE/G of dry plant) and flavonoids (60 mg QE/g of quercetin dry plant). The CCl4 (0.5 ml/kg) treated rats exhibited significant reductions in serum vitamin A (VA), vitamin E (VE) and total antioxidant status (TAS). Thiobarbituric acid reactive substances (TBARS) and conjugated dienes (CD) were significantly high in the CCl4 group compared to controls. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were significantly decreased in CCl4 rats. Cytogenetic trials revealed remarkable increases in the frequency of chromosomal aberrations (CAs) and sister chromatid exchange (SCE) following CCl4 administration. Pretreatment with TP prevented damages caused by CCl4. Spleen characterised by necrosis was detected in CCl4 as compared to controls. Pretreatment with TP considerably decreased the perturbation.


Rethinking electronic health records to better achieve quality and safety goals.
Health care information technology changes the ecosystem of a practice. Human roles, process work flow, and technology infrastructure are tightly interrelated. Medical errors may increase if a change in one is not accommodated by a change in the others. Introduction of information technology should be approached as an iterative process of care improvement rather than as a one-time insertion of an information system into established practice. Information technology supports a family of technological approaches, each with distinct mechanisms of action, benefits, and side effects. By matching technological approach to task and staging introduction into practice, initial benefit can be obtained more quickly, at reduced cost, while managing risk of a misfit. A staged approach to turning direct access by patients to their health information into more effective care is presented as an example of this strategy.


A comparison of oncologist versus mental health provider attitudes towards standardized and tailored patient-reported outcomes.
Patient-reported outcomes (PROs) can be used to monitor patients during treatment. Healthcare provider preferences for individualized vs. standardized PROs have been understudied. This study surveyed oncology and mental health providers to compare attitudes towards individualized and standardized PROs. We have developed a method for individualizing PROs, called precision PROs, and the survey specifically assessed preferences for this method. We compared attitudes and preferences by provider type and by whether respondents were current or never users of PROs. Oncology providers expressed more positive attitudes for standardized PROs in treatment planning compared to mental health providers (F(1,440) = 5.978, p = 0.015). The interaction between provider type (oncology vs. mental health) and type of PRO (individualized vs. standardized) was not significant for the attitudes about the clinical utility of PROs (p = 0.709). When directly asked about the precision PRO approach, oncologists were less likely to prefer standardized items (OR = 0.478, p = 0.001) or have no preference (OR = 0.445, p = 0.007) to the precision PRO approach when compared to mental health providers. Qualitative analyses suggested standardized PROs may be simpler or easier to understand whereas individualized PROs better capture patient variability and the unique aspects of each patient's condition. Some mental health providers expressed reticence about letting patients choose how to tailor PROs. Never users of PROs reported more positive attitudes towards individualized measures than standardized measures whereas current users of PROs did not have a difference in attitudes (p = 0.010). User status was mostly unrelated to preferences. Results suggest that healthcare provider preference for individualized PROs may differ by medical specialty. How PROs are tailored may need to differ by discipline. This is particularly important given that previous research showing a preference for individualized PROs over standardized was conducted with psychotherapists. Further research on patient preferences for individualized and standardized PROs is warranted as is research on the clinical utility of individualized PROs such as the precision PRO approach.


[New guideline for the management of hyperlipidemia according to patient category and global risk chart].
Risk charts for predicting coronary heart disease(CHD) based on the Framingham Study are not valid for other ethnic people including Japanese, and no large scale prospective study exists which has examined the relationship between coronary risk factors and the incidence of CHD in Japan. The Japan Lipid Intervention Trial(J-LIT) is a 6-year prospective study of simvastatin therapy for mild hypercholesterolemia in a clinical setting. Major coronary events were observed in 336 patients in the primary prevention cohort(47,294) and 102 patients in the secondary prevention cohort(5,127) during the study period. Consequently we were able to create easy-to-use charts that predict the absolute risk of developing a coronary event based on determinable risk factors. Absolute risks were lower than predicted by the Framingham formula. The J-LIT charts demonstrate absolute and relative risks for primary and secondary coronary events in Japanese patients. Their use should help individualize risk factor management.


Nursing students' perceptions of clinical experience.
Senior nursing students were interviewed in this study to better understand the clinical learning experience from the students' point of view. Results of the study revealed that the nursing students were indeed learning in their clinical experience. The major categories of learning were classified as nursing skills, time management, and professional socialization. The quality of learning was reportedly affected by the quality of the student's preparation, characteristics of the instructor, and the variety of clinical opportunities to which students were exposed. The data also reflected a pattern of student development which was separated into three stages. The first stage was permeated with anxiety and obsession with the rules of task performance. The second stage was a difficult transition period where students struggled with identifying the roles of nurses. During the final stage, the students become more comfortable with performing nursing tasks and become interested in expanding their role and becoming more independent. As the students strived for independence, they identified more closely with staff nurses and withdrew from instructors.


Optical triangulation-based microtopographic inspection of surfaces.
The non-invasive inspection of surfaces is a major issue in a wide variety of industries and research laboratories. The vast and increasing range of surface types, tolerance requirements and measurement constraints demanded during the last decades represents a major research effort in the development of new methods, systems and metrological strategies. The discreet dimensional evaluation the rugometric characterization and the profilometric inspection seem to be insufficient in many instances. The full microtopographic inspection has became a common requirement. Among the different systems developed, optical methods have the most important role and among those triangulation-based ones have gained a major status thanks to their flexibility, reliability and robustness. In this communication we will provide a brief historical review on the development of optical triangulation application to the dimensional inspection of objects and surfaces and on the work done at the Microtopography Laboratory of the Physics Department of the University of Minho, Portugal, in the development of methods and systems of optical triangulation-based microtopographic inspection of surfaces.


Subcellular distribution of S100A4 and its transcriptional regulation under hypoxic conditions in gastric cancer cell line BGC823.
It is well known that S100A4 is overexpressed in many tumors and involved in tumor invasion and metastasis. But the regulation of it is ill understood. We previously found that hypoxia mimicking cobalt chloride (CoCl(2)) enhanced the mRNA and protein expressions of the S100A4 gene in the gastric cancer cell line BGC823. In this study we found that S100A4 also displayed increased expression in BGC823 cells after exposure to real hypoxia (2.5% O(2)) as that by CoCl(2) treatment. Moreover, S100A4 protein showed different subcellular distribution under real hypoxia compared with that by CoCl(2) treatment or in normoxic conditions. To investigate the underlying molecular mechanism by which hypoxia regulates the expression of S100A4, we analyzed the regulatory sequences of the genes by bioinformatics and found a putative hypoxia responsive element (HRE) motif in the first intron of S1004. Furthermore, luciferase reporter assay showed that it is responsive to hypoxia. Electrophoretic mobility shift assay and chromatin immunoprecipitation assays demonstrated that hypoxia-inducible factor 1 (HIF-1) binds to the functional HRE in vitro and in vivo. The results provide evidence that S100A4 is a hypoxia-inducible gene, whose transcription is stimulated at least partly through the interaction of HIF-1 and HRE located at +329 to +334 of S100A4.


Trichloroacetic Acid Fixation and Antibody Staining of Zebrafish Larvae.
Larval zebrafish have been established as an excellent model for examining vertebrate biology, with many researchers using the system for neuroscience. Controlling a fast escape response of the fish, the Mauthner cells and their associated network are an attractive model, given their experimental accessibility and fast development, driving ethologically relevant behavior in the first five days of development. Here, we describe methods for immunostaining electrical and chemical synapse proteins at 3-7 days post fertilization (dpf) in zebrafish using tricholoracetic acid fixation. The methods presented are ideally suited to easily visualize neural circuits and synapses within the fish.


Gene loss and adaptation to hominids underlie the ancient origin of HIV-1.
HIV-1 resulted from cross-species transmission of SIVcpz, a simian immunodeficiency virus that naturally infects chimpanzees. SIVcpz, in turn, is a recombinant between two SIV lineages from Old World monkeys. Lentiviral interspecies transmissions are partly driven by the evolution and capacity of viral accessory genes, such as vpx, vpr, and vif, to antagonize host antiviral factors, such as SAMHD1 and the APOBEC3 proteins. We show that vpx, which in other lentiviruses antagonizes SAMHD1, was deleted during the creation of SIVcpz. This genomic deletion resulted in the reconstruction of the overlapping vif gene by "overprinting," creating a unique vif that overlaps in its 3' end with the vpr gene and can antagonize hominid APOBEC3s. Moreover, passage of SIVs through chimpanzees facilitated the subsequent adaptation of HIV-1 to humans. Thus, HIV-1 originated through a series of gene loss and adaptation events that generated its chimpanzee precursor and lowered the species barrier to human infection.


Genetic interactions between the chromosome axis-associated protein Hop1 and homologous recombination determinants in Schizosaccharomyces pombe.
Hop1 is a component of the meiosis-specific chromosome axis and belongs to the evolutionarily conserved family of HORMA domain proteins. Hop1 and its orthologs in higher eukaryotes are a major factor in promoting double-strand DNA break formation and inter-homolog recombination. In budding yeast and mammals, they are also involved in a meiotic checkpoint kinase cascade monitoring the completion of double-strand DNA break repair. We used the fission yeast, Schizosaccharomyces pombe, which lacks a canonical synaptonemal complex to test whether Hop1 has a role beyond supporting the generation of double-strand DNA breaks and facilitating inter-homolog recombination events. We determined how mutants of homologous recombination factors genetically interact with hop1, studied the role(s) of the HORMA domain of Hop1, and characterized a bio-informatically predicted interactor of Hop1, Aho1 (SPAC688.03c). Our observations indicate that in fission yeast, Hop1 does require its HORMA domain to support wild-type levels of meiotic recombination and localization to meiotic chromatin. Furthermore, we show that hop1∆ only weakly interacts genetically with mutants of homologous recombination factors, and in fission yeast likely has no major role beyond break formation and promoting inter-homolog events. We speculate that after the evolutionary loss of the synaptonemal complex, Hop1 likely has become less important for modulating recombination outcome during meiosis in fission yeast, and that this led to a concurrent rewiring of genetic pathways controlling meiotic recombination.


Overexpression of P2X4 receptor in Schwann cells promotes motor and sensory functional recovery and remyelination via BDNF secretion after nerve injury.
Of the seven P2X receptor subtypes, P2X4 receptor (P2X4R) is widely distributed in the central nervous system, including in neurons, astrocytes, and microglia. Accumulating evidence supports roles for P2X4R in the central nervous system, including regulating cell excitability, synaptic transmission, and neuropathic pain. However, little information is available about the distribution and function of P2X4R in the peripheral nervous system. In this study, we find that P2X4R is mainly localized in the lysosomes of Schwann cells in the peripheral nervous system. In cultured Schwann cells, TNF-a not only enhances the synthesis of P2X4R protein but also promotes P2X4R trafficking to the surface of Schwann cells. TNF-a-induced BDNF secretion in Schwann cells is P2X4R dependent. in vivo experiments reveal that expression of P2X4R in Schwann cells of injured nerves is strikingly upregulated following nerve crush injury. Moreover, overexpression of P2X4R in Schwann cells by genetic manipulation promotes motor and sensory functional recovery and accelerates nerve remyelination via BDNF release following nerve injury. Our results suggest that enhancement of P2X4R expression in Schwann cells after nerve injury may be an effective approach to facilitate the regrowth and remyelination of injured nerves.


Photoreceptor inner segment ellipsoid band integrity on spectral domain optical coherence tomography.
Spectral domain optical coherence tomography cross-sectional imaging of the macula has conventionally been resolved into four bands. However, some doubts were raised regarding authentication of the existence of these bands. Recently, a number of studies have suggested that the second band appeared to originate from the inner segment ellipsoids of the foveal cone photoreceptors, and therefore the previously called inner segment-outer segment junction is now referred to as inner segment ellipsoidband. Photoreceptor dysfunction may be a significant predictor of visual acuity in a spectrum of surgical and medical retinal diseases. This review aims to provide an overview and summarizes the role of the photoreceptor inner segment ellipsoid band in the management and prognostication of various vitreoretinal diseases.


Neuromodulation for treatment-resistant depression: Functional network targets contributing to antidepressive outcomes.
Non-invasive brain stimulation is designed to target accessible brain regions that underlie many psychiatric disorders. One such method, transcranial magnetic stimulation (TMS), is commonly used in patients with treatment-resistant depression (TRD). However, for non-responders, the choice of an alternative therapy is unclear and often decided empirically without detailed knowledge of precise circuit dysfunction. This is also true of invasive therapies, such as deep brain stimulation (DBS), in which responses in TRD patients are linked to circuit activity that varies in each individual. If the functional networks affected by these approaches were better understood, a theoretical basis for selection of interventions could be developed to guide psychiatric treatment pathways. The mechanistic understanding of TMS is that it promotes long-term potentiation of cortical targets, such as dorsolateral prefrontal cortex (DLPFC), which are attenuated in depression. DLPFC is highly interconnected with other networks related to mood and cognition, thus TMS likely alters activity remote from DLPFC, such as in the central executive, salience and default mode networks. When deeper structures such as subcallosal cingulate cortex (SCC) are targeted using DBS for TRD, response efficacy has depended on proximity to white matter pathways that similarly engage emotion regulation and reward. Many have begun to question whether these networks, targeted by different modalities, overlap or are, in fact, the same. A major goal of current functional and structural imaging in patients with TRD is to elucidate neuromodulatory effects on the aforementioned networks so that treatment of intractable psychiatric conditions may become more predictable and targeted using the optimal technique with fewer iterations. Here, we describe several therapeutic approaches to TRD and review clinical studies of functional imaging and tractography that identify the diverse loci of modulation. We discuss differentiating factors associated with responders and non-responders to these stimulation modalities, with a focus on mechanisms of action for non-invasive and intracranial stimulation modalities. We advance the hypothesis that non-invasive and invasive neuromodulation approaches for TRD are likely impacting shared networks and critical nodes important for alleviating symptoms associated with this disorder. We close by describing a therapeutic framework that leverages personalized connectome-guided target identification for a stepwise neuromodulation paradigm.