The ESCRT protein Chmp4c regulates mitotic spindle checkpoint signaling.
The mitotic spindle checkpoint delays anaphase onset in the presence of unattached kinetochores, and efficient checkpoint signaling requires kinetochore localization of the Rod-ZW10-Zwilch (RZZ) complex. In the present study, we show that human Chmp4c, a protein involved in membrane remodeling, localizes to kinetochores in prometaphase but is reduced in chromosomes aligned at the metaphase plate. Chmp4c promotes stable kinetochore-microtubule attachments and is required for proper mitotic progression, faithful chromosome alignment, and segregation. Depletion of Chmp4c diminishes localization of RZZ and Mad1-Mad2 checkpoint proteins to prometaphase kinetochores and impairs mitotic arrest when microtubules are depolymerized by nocodazole. Furthermore, Chmp4c binds to ZW10 through a small C-terminal region, and constitutive Chmp4c kinetochore targeting causes a ZW10-dependent checkpoint metaphase arrest. In addition, Chmp4c spindle functions do not require endosomal sorting complex required for transport-dependent membrane remodeling. These results show that Chmp4c regulates the mitotic spindle checkpoint by promoting localization of the RZZ complex to unattached kinetochores.


Modulation of LDL catabolism by sodium nitroprusside and PGE2 in human peripheral blood lymphocytes.
The effect of nitric oxide donor--sodium nitroprusside (NaNP) and PGE2 on the LDL-receptor activity and LDL cellular accumulation by isolated human blood lymphocytes was investigated. Preincubation of lymphocytes with lipoprotein deficient medium (LPDS) resulted in the increase of the LDL-receptor activity and the LDL-cellular accumulation. NaNP (30-300 microM) dose-dependently prevented the increase of the LDL-receptor activity as well as the accumulation of LDL by lymphocytes. However, in "starwing" cells (cells with high LDL-receptor activity) the effect of NaNP on the receptor activity was biphasic. At concentration up to 100 microM NaNP inhibited, while at a concentration of 300 microM, it activated the LDL-receptor activity. PGE2 (3-30 microM) inhibited LDL catabolism, however, this effect was hardly concentration-dependent.


Strain-specific telomere length revealed by single telomere length analysis in Caenorhabditis elegans.
Terminal restriction fragment analysis is the only method currently available for measuring telomere length in Caenorhabditis elegans. Its limitations include low sensitivity and interference by the presence of interstitial telomeric sequences in the C.elegans genome. Here we report the adaptation of single telomere length analysis (STELA) to measure the length of telomeric repeats on the left arm of chromosome V in C.elegans. This highly sensitive PCR-based method allows telomere length measurement from as few as a single worm. The application of STELA to eight wild-type C.elegans strains revealed considerable strain-specific differences in telomere length. Within individual strains, short outlying telomeres were observed that were clearly distinct from the bulk telomere length distributions, suggesting that processes other than end-replication losses and telomerase-mediated lengthening may generate telomere length heterogeneity in C.elegans. The utility of this method was further demonstrated by the characterization of telomere shortening in mrt-2 mutants. We conclude that STELA appears to be a valuable tool for studying telomere biology in C.elegans.


Evaluation of serum Neuron-specific enolase, S100B, myelin basic protein and glial fibrilliary acidic protein as brain specific proteins in children with autism spectrum disorder.
Brain specific-proteins are not found in other tissues and measurement non-invasively in the blood may identify structurally and functionally damaged brain regions and identify the severity and prognosis of neuropsychiatric diseases. For this reason, we aimed to evaluate serum brain-specific protein values as brain damage markers in children with autism spectrum disorder (ASD). 35 children with ASD and 31 healthy subjects were included in the study. Sociodemographic form and Childhood Autism Rating Scale (CARS) were applied to each subject. Serum neuron specific enolase (NSE), S100B, Myelin basic protein (MBP) and Glial fibrillary acidic protein (GFAP) values were measured with ELISA. There was no significant difference between the two groups for NSE, MBP and S100B values (p=0.242; p=0.768; p=0.672, respectively). However, GFAP values in the patient group were statistically significantly higher (mean±SD: 0.463±0.392ng/ml) than in the healthy control group (mean±SD: 0.256±0.111ng/ml) (p<0.001). In addition, there was a significant positive correlation between serum GFAP values and CARS score in all subjects and in the patient group (r=0.599; p<0.001 and r=0.380; p=0.024, respectively). While serum NSE, MBP, and S100B values cannot be considered as biomarkers for ASD, GFAP may be a biomarker and is suggested as a possible indicator of autism severity.


Massive pneumatosis without necrosis: A case report of Clostridium perfringens sepsis in an extremely low birth weight infant.
Pneumatosis intestinalis and free intraperitoneal air on abdominal radiographs are considered pathognomonic signs of necrotizing enterocolitis (NEC). We report a unique case of late-onset fulminant sepsis due to Clostridium perfringens presenting with shock, extensive pneumatosis intestinalis and free intraperitoneal air in an extremely low birth weight infant without histopathological evidence of bowel necrosis or NEC.


Silicone intubation as an alternative to dacryocystorhinostomy for nasolacrimal drainage obstruction in adults.
Silicone tubing was used to repair the patency of the nasolacrimal drainage system in 115 patients (four bilaterally) with chronic nasolacrimal duct obstruction. The patients were over 20 years old and 16 were men and 99 women; 46% presented an uncomplicated obstruction with epiphora and 54% presented additional signs of chronic dacryocystitis. We used the technique of Quickert and Dryden with modifications. The silicone tube remained for a mean of 5.5 months (+/- 2.5 SD). After removal of the tube the follow-up ranged from 6 to 42 months (mean +/- SD: 16 +/- 9). Patency was maintained in 89% of cases with uncomplicated obstruction and in 69% of those with chronic dacryocystitis (total success rate 78%). We can therefore recommend silicone intubation of the lacrimal drainage system as an alternative to dacryocystorhinostomy (DCR), in adults with obstruction of the nasolacrimal duct. In addition, unlike DCR this technique is bloodless and the operation takes less time.


A QTL that enhances and broadens Bt insect resistance in soybean.
Effective strategies are needed to manage insect resistance to Bacillus thuringiensis (Bt) proteins expressed in transgenic crops. To evaluate a multiple resistance gene pyramiding strategy, eight soybean (Glycine max) lines possessing factorial combinations of two quantitative trait loci (QTLs) from plant introduction (PI) 229358 and a synthetic Bt cry1Ac gene were developed using marker-assisted selection with simple sequence repeat markers. Field studies were conducted in 2000 and 2001 to evaluate resistance to corn earworm (Helicoverpa zea) and soybean looper (Pseudoplusia includens), and detached leaf bioassays were used to test antibiosis resistance to Bt-resistant and Bt-susceptible strains of tobacco budworm (TBW; Heliothis virescens). Based on defoliation in the field and larval weight gain on detached leaves, lines carrying a combination of cry1Ac and the PI 229358 allele at a QTL on linkage group M were significantly more resistant to the lepidopteran pests, including the Bt-resistant TBW strain, than were the other lines. This is the first report of a complementary additive effect between a Bt transgene and a plant insect resistance QTL with an uncharacterized mode of action that was introgressed using marker-assisted selection.


Spontaneous conversion to estrogen receptor expression by the human breast epithelial cell line, MCF-10A.
The human breast epithelial cell line, MCF-10A, derived from tissue from a woman undergoing a cutaneous mastectomy for fibrocystic breast disease, is negative for estrogen receptor expression, has undergone minimal genetic changes, retains many of the characteristics of normal breast epithelium and fails to exhibit growth in nude mice. When transfected with a functional copy of the estrogen receptor, both ER and MDM2 expression are negatively regulated by the presence of increasing concentrations of estradiol, as previously reported. We obtained the MCF-10A cell line from the American Type Culture Collection and confirmed that it was negative for ER expression. After approximately 20 passages under differing growth conditions, one subline was determined to be positive for ER expression. Growth of this ER-positive subline in phenol red-free media supplemented with charcoal-dextran stripped serum in the presence of nanomolar concentrations of estradiol failed to modulate ER and MDM2 expression, and induced expression of both pS2 and cathepsin D. Simultaneously with these observations, we observed that this subline, unlike the parent MCF-10A line, overexpressed P53 protein with a nuclear localization. Intermediate levels of the P53-inducible protein p21 WAF1/Cip1 were also detected in the ER-positive subline whereas levels of this protein in the parent subline were barely detectable, as measured by immunohistochemical methods. We conclude from these studies that ER expression and P53 alteration may constitute early steps in progression of malignant potential for breast cancer development.


Unconventional Cadherin Localization in Honey Bee Gonads Revealed Through Domain-Specific Apis mellifera E- and N-Cadherin Antibodies Indicates Alternative Functions.
As key factors in intercellular adhesion processes, cadherins play important roles in a plethora of developmental processes, including gametogenesis. In a previous study on cadherin localization in the gonads of honey bees, performed with heterologous pan-cadherin antibodies, we detected these proteins as (i) associated with cell membranes, (ii) as homogeneously distributed throughout the cytoplasm, and (iii) as nuclear foci in both somatic and germline cells, raising the possibility of alternative functions. To further investigate such unusual intracellular cadherin localization we produced specific antibodies against the N- and C-terminal domains of honey bee N- and E-cadherin. A 160 kDa protein was recognized by the E-cadherin antibodies as well as one of approximately 300 kDa from those raised against N-cadherin. In gonad preparations, both proteins were detected as dispersed throughout the cytoplasm and as nuclear foci in both germline and somatic cells of queen and worker ovarioles, as well as in the testioles of drones. This leads us to infer that cadherins may indeed be involved in certain signaling pathways and/or transcriptional regulation during gametogenesis. In late oogenesis stages, immunolabeling for both proteins was observed at the cell cortex, in conformity with a role in cell adhesion. In testioles, E-cadherin was seen in co-localization with fusomes, indicating a possible role in cyst organization. Taken together, the distribution of N- and E-cadherins in honey bee gonads is suggestive of alternative roles for cadherins in gametogenesis of both sexes.


[Analysis of type II pneumocyte protection by pneumoplegic solutions. An experimental in vitro study of lung preservation for transplantation].
With the aim of studying the physiopathological mechanism of lung preservation, we have valued the Pneumocytes Type II viability after six hours of incubation at 4 degrees C in extracellular (Ringer Lactate) and intracellular (Collins, Euro-Collins and Belzer) solutions. The cells have been cut off from adult rat's lung using the modified Dobbs' method. Alveolar Type II viability have been valued using two methods: the total protein content in each culture and the metabolic function of the cells using the rate of protein synthesis by means of 35 S methionine uptake assay. The results have demonstrated a significant difference (p < 0.05) using extracellular solution instead of intracellular. Besides, we have observed a better Pneumocytes Type II survival during Belzer's solution incubation comparing with Collins and Euro-Collins (p < 0.05). Pneumocytes type II require for a better preservation a specific solution that must be similar to extracellular fluid and added with substances able to minimize noxious events during preservation.


How to target small cell lung cancer.
Small cell lung cancer (SCLC) is a highly malignant disease with dismal prognosis. Although great progress has been made in investigating genetic aberrations and putative drivers of this tumor entity, the mechanisms of rapid dissemination and acquisition of drug resistance are not clear. The majority of SCLC cases are characterized by inactivation of the tumor suppressors p53 and retinoblastoma (Rb) and, therefore, interchangeable drivers will be difficult to target successfully. Access to pure cultures of SCLC circulating tumor cells (CTCs) and study of their tumor biology has revealed a number of new potential targets. Most important, expression of chitinase-3-like-1/YKL-40 (CHI3L1) which controls expression of vascular epithelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP9) was newly described in these cells. The process switching CHI3L1-negative SCLC cells to CHI3L1-positive CTCs seems to be associated with cytokines released by inflammatory immune cells. Furthermore, these CTCs were found to promote monocyte-macrophage differentiation, most likely of the M2 tumor-promoting type, recently described to express PD-1 immune checkpoint antigen in SCLC. In conclusion, dissemination of SCLC seems to be linked to conversion of regular tumor cells to highly invasive CHI3L1-positive CTCs, which are protected by immune system suppression. Besides the classical targets VEGF, MMP-9 and PD-1, CHI3L1 constitutes a new possibly drugable molecule to retard down dissemination of SCLC cells, which may be similarly relevant for glioblastoma and other tumor entities.


Research on Assistant Diagnosis of Fundus Optic Neuropathy Based on Deep Learning.
The purpose of this study was to use the neural network to distinguish optic edema (ODE), and optic atrophy from normal fundus images and try to use visualization to explain the artificial intelligence methods. Three hundred and sixty-seven images of ODE, 206 images of optic atrophy, and 231 images of normal fundus were used, which were provided by two hospitals. A set of image preprocessing and data enhancement methods were created and a variety of different neural network models, such as VGG16, VGG19, Inception V3, and 50-layer Deep Residual Learning (ResNet50) were used. The accuracy, recall, F1-score, and ROC curve under different networks were analyzed to evaluate the performance of models. Besides, CAM (class activation mapping) was utilized to find the focus of neural network and visualization of neural network with feature fusion. Our image preprocessing and data enhancement method significantly improved the accuracy of model performance by about 10%. Among the networks, VGG16 had the best effect, as the accuracy of ODE, optic atrophy and normal fundus were 98, 90, and 95%, respectively. The macro-average and micro-average of VGG16 both reached 0.98. From CAM we can clearly find out that the focus area of the network is near the optic cup. From feature fusion images, we can find out the difference between the three types fundus images. Through image preprocessing, data enhancement, and neural network training, we applied artificial intelligence to identify ophthalmic diseases, acquired the focus area through CAM, and identified the difference between the three ophthalmic diseases through neural network middle layers visualization. With the help of assistant diagnosis, ophthalmologists can evaluate cases more precisely and more clearly.


Fibre glass induced synovitis.
Chronic synovitis developed in the dorsal extensor sheath of the hand of a 25-year-old manufacturer of fibre glass reinforced boats and surfboards . Particles found in synovial fluid aspirates were similar in morphology and elemental content to unused fibre glass and particles found in dust from the workshop floor. It was concluded that hard disc grinding required during manufacture resulted in percutaneous implantation of small glass particles, leading to chronic synovitis and effusion.


External beam radiotherapy for prostate cancer.
External beam radiotherapy (EBRT) constitutes an important management option for prostate cancer (PCa). Radiation doses >or=74 Gy are warranted. Dose escalation of EBRT using three-dimensional-conformal radiotherapy (RT) or intensity-modulated RT improves the therapeutic index by minimizing normal tissue complication probability and increasing tumor control probability. Although higher doses are associated with better biochemical disease-free survival, no impact on local recurrence or overall survival has been demonstrated. Hypofractionation for PCa may be an attractive therapeutic option, but toxicity data need to be confirmed in randomized phase III trials. Advances in RT technology, such as volumetric modulated arc therapy and image-guided RT, could facilitate the introduction of dose escalation and hypofractionation into clinical practice. Particle beam irradiation and more specific carbon ion RT are also very promising new techniques that are under investigation. Ultimately, these techniques may lead to focal dose escalation by selective boosting of dominant intraprostatic lesions, which is currently under investigation as a solution to overcome increased toxicity of homogenous dose escalation. This review will give a comprehensive overview of all the recent advances in these new radiation therapy techniques.


Immobilization on chitosan of a thermophilic trehalose synthase from Thermus thermophilus HJ6.
A thermostable trehalose synthase (TtTSase) from Thermus thermophilus HJ6 was immobilized on chitosan activated with glutaraldehyde. The yield of immobilization was evaluated as 39.68%. The optimum pH of the immobilized enzyme was similar to that of the free enzyme. However, the optimal temperature ranges were shifted by about 4 degrees C owing to better thermal stability after immobilization. The half-life of heat inactivation for free and immobilized enzymes was 5.7 and 6.3 days at 70 degrees C, respectively, thus showing a lager thermostability of the immobilized enzyme. When tested in batch reaction, the immobilized enzyme retained its relative activity of 53% after 30 reuses of reaction within 12 days, and still retained 82% of its initial activity even after 150 days at 4 degrees C. A packed-bed bioreactor with immobilized enzyme showed a maximum yield of 56% trehalose from 100 mM maltose in a continuous recycling system (bed volume: 10 ml) under conditions of pH 7.0 and 70 degrees C.


A meaningful clinical experience in home healthcare for associate degree graduate nurses.
Associate degree nursing (ADN) students need exposure to community-based clinical settings to prepare them for changing practice environments. In response to that need, a discrete, clinically-focused, home healthcare course was developed and offered to recent ADN graduate nurses. Emphasis was placed on active participation of the client and family in care giving activities. Students were involved in teaching and demonstration, coordination of resources, and relevant referrals. Appropriate documentation with a focus on Medicare reimbursement issues was included.


Alterations of Interhemispheric Functional Connectivity in Parkinson's Disease With Depression: A Resting-State Functional MRI Study.
Depression is the most common non-motor symptom in patients with Parkinson's disease (PD) with unknown mechanisms, but the diagnostic criteria of PD with depression (PDD) are not uniform. The aim of the study was to investigate interhemispheric interactions between PDD patients and patients with PD without depression (PDND). The voxel-mirrored homotopic connectivity (VMHC) combined with the seed-based method was used to investigate intrinsic resting-state functional connectivity (RSFC) in 33 PDD patients, 60 PDND, and 47 healthy controls (HCs). PDD patients exhibited a decreased VMHC in the bilateral medial frontal gyrus and paracentral lobule (MFG/PCL) than did PDND patients. Parkinson's disease with depression had a decreased VMHC in the bilateral precentral gyrus than had PDND and HC (p < 0.05). Parkinson's disease with depression had a decreased homotopic RSFC from the medial frontal gyrus (MFG)/PCL to the contralateral supplementary motor area (SMA) than had PDND (p < 0.05). The decreased homotopic RSFC from the right MFG/PCL to the left SMA was negatively correlated with Hamilton Depression Rating Scale scores (p < 0.05), but not with illness duration, Beck's Depression Inventory, and Unified Parkinson's Disease Rating Scale in PD patients. Our findings indicated that the occurrence of depression in Parkinson's disease is associated with the dysfunctional connectivity from the MFG/PCL to the contralateral SMA, which could be used as potential neuroimaging markers for the diagnosis of depression in PD patients.


Opioid Prescribing by Dentists in the Veterans Health Administration.
Nonopioid analgesics are more effective for most oral pain, but data suggest that dental prescribing of opioids is excessive. This study evaluates the extent to which opioids exceed recommendations and the characteristics associated with opioid overprescribing by Veterans Health Administration dentists. This was a national cross-sectional study of Veterans' dental visits from 2015 to 2018. Overprescribing was defined per national guidelines as >120 morphine milligram equivalents (primary outcome). The association of dental visit and patient demographic and medical characteristics was modeled with overprescribing (defined as >120 morphine milligram equivalents) using Poisson regression with clustering by facility and patient. A secondary analysis assessed opioid prescriptions >3 days' supply. The dates of analysis were January 2020‒May 2021. Of the 196,595 visits, 28.7% exceeded 120 morphine milligram equivalents. Friday visits and people with chronic oral pain or substance misuse were associated with a higher prevalence of overprescribing. Women, older Veterans, and Black and Latinx Veterans were less likely to be overprescribed than men, younger Veterans, and White Veterans, respectively. Routine dental visits had a higher prevalence of opioid overprescribing than invasive visits. Opioid overprescribing decreased over time. White Veterans were more likely to receive oxycodone and hydrocodone, whereas people of Black race and Latinx ethnicity were more likely to receive codeine and tramadol. In the secondary analysis, 68.5% of opioid prescriptions exceeded a 3-day supply. Nearly 1 in 3 opioids prescribed by Veterans Health Administration dentists exceed guidelines. Prescribing higher potency and quantities of opioids, especially on Fridays and to certain demographic groups, should be addressed as part of dental opioid stewardship programs.


Engineering Lewis Acidity in Zeolite Catalysts by Electrochemical Release of Heteroatoms during Synthesis.
The creation of heteroatom nodes in zeolite frameworks is a challenging but rewarding pathway to superior materials for numerous catalytic applications. Here, we present a novel method for precise control over heteroatom incorporation by in situ anodic release of a desired metal during hydrothermal zeolite synthesis. The generic character of the technique and the applicability of the new synthesis reactor are shown across 3 zeolite structures crystallized and 4 electrode metals in two pH zones and by offering access to a new mixed-metal zeolite. The timed and voltage-controlled metal release offers a minimized interference between the metal precursor state and critical events in the zeolite's crystallization. A mechanistic study for Sn-MFI revealed the key importance of controlled release: while keeping its concentration lower than in batch, a lot more Sn can be incorporated into the framework. The method grants access to 10× increased framework Lewis acid site densities (vs batch controls) for the most relevant stannosilicates. As a proof, the electro-made materials demonstrate higher productivity than their classic counterparts in lactate catalysis. This innovative approach effectively expands the synthesis space of zeolites.


On the accessibility of phosphatidylglycerol to periodate in Escherichia coli.
The transverse distribution of phosphatidylglycerol (PG) across the inner membrane of Escherichia coli was studied. The oxidation of PG by periodate was used to discriminate between the PG present in the cytoplasmic and in the periplasmic leaflet of the inner membrane. Applied to large unilamellar vesicles derived of an E. coli lipid extract, the periodate method demonstrated the expected symmetrical distribution of PG over the bilayer. However, both in right-side-out and in inside-out inner membrane vesicles isolated from E. coli, as well as in intact E. coli cells, the entire pool of PG was oxidized by periodate. The oxidation reaction proceeded at such a high rate that it was impossible to determine the distribution of PG across the membrane. Apparently, periodate easily permeates through the membrane. This permeation could not be inhibited or slowed down, and it was concluded that the use of periodate as oxidizer of PG is not a suitable method to determine the transverse distribution of this phospholipid in the Gram-negative bacterium E. coli. However, periodate can be used to selectively modify the total PG pool in this organism.


Low Energy Positron Scattering by F and F2.
We have determined integral and differential elastic cross sections for positron scattering with atomic F and F2 molecules from 0.01 to 1000 eV with different theoretical approaches. Higher order polarizabilities were successively considered in the scattering potential, and we observed that the differential and integral cross sections converge only when the pure dipole second hyperpolarization level is taken into account, demonstrating the importance of the hyperpolarization effects on the low energy positron scattering dynamics. Ramsauer structures were found for both targets, and in the particular case of the F atom, the effect of its quadrupole moment proved to be relevant around the position of the Ramsauer minimum, which was determined together with the scattering length for each of the adopted polarization schemes. A relation of these quantities with the matching radius between the correlation and polarization interactions is also discussed. Agreement between the model potential and ab initio cross sections for the lowest level of target polarization is found for F2. Since there is no previous theoretical or experimental determination of cross sections for these targets, we compared the differential cross sections of F2 with experimental data available for N2 and O2 and found reasonable agreement.


Polymorphism of p53 gene codon 72 in endometrial cancer: correlation with tumor grade and histological type.
Endometrial cancer is the fourth most common cancer among women in developed countries. Patients with endometrial cancer may benefit from systemic chemotherapy alone or in combination with targeted therapies if the disease is clinically diagnosed prior to spread and metastasis to other organs. The aim of this study was to evaluate the prognostic role of p53 polymorphism and its correlation with tumor grade in human uterine endometrial carcinomas. A total of 75 patients with endometrial carcinomas were studied for possible mutations in exon 4 of the p53 gene using polymerase chain reaction and restricting fragment length polymorphism techniques and sequencing. In recent study, The rate of homozygote genotype of pro/pro or Arg/Arg in high grade group was higher than in comparison with low grade one. In addition samples that were undigested in RFLP, showed mutation in exone 4. Our findings showed that high grade endometrial carcinomas are highly associated with TP53 polymorphisms in comparison with low grades.


Severe alpha-1 antitrypsin deficiency in composite heterozygotes inheriting a new splicing mutation QOMadrid.
Severe Alpha-1 Antitrypsin (AAT) deficiency is a hereditary condition caused by mutations in the SERPINA1 gene, which predisposes to lung emphysema and liver disease. It is usually related to PI*Z alleles, and less frequent to rare and null (QO) alleles. Null-AAT alleles represent the end of a continuum of variants associated with profound AAT deficiency and extremely increased risk of emphysema. A family with severe AAT deficiency was analyzed to achieve genetic diagnosis. The complete exons and introns of the SERPINA1 gene were sequenced and transcriptional analysis by RT-PCR was performed to characterize the effect of splicing variants found in the patients. In addition, a minigene MGserpa1_ex1b-1c was cloned into the pSAD vector to in vitro investigate the independent impact of variants on splicing process. We report a new identified null allele (PI*QOMadrid) in two adult siblings with practically no detectable serum AAT. The PI*QOMadrid allele consist of a duplication of the thymine (T) in position +2 of the donor splice site of exon 1C (+2dupT). In these two subjects, PI*QOMadrid occurred in compound heterozygote combination with the previously described variant PI*QOPorto. Both QOMadrid and QOPorto variants are located very close together in a regulatory region of the SERPINA1 gene. Analysis of transcripts revealed that QOMadrid variant prevented the expression of transcripts from exon 1C, and then normally spliced RNA products are not expected in the liver of these patients. In addition, aberrant splicing patterns of both variants were clearly distinguished and quantified by functional in vitro assays lending further support to their pathogenicity. Finding pathogenic mutations in non-coding regions of the SERPINA1 highlight the importance that regulatory regions might have in the disease. Regulatory regions should be seriously considered in discordant cases with severe AAT deficiency where no coding mutations were found.


Evaluating the Efficacy of a Narrative Language Intervention for Bilingual Students.
This study examines the narrative language and reading outcomes of monolingual and bilingual students who received instruction with the Supporting Knowledge in Language and Literacy (SKILL) program, a narrative language intervention. The main effects of the SKILL program were evaluated in a randomized controlled trial in which students (N = 355) who were at risk for English language and literacy difficulties were randomized to the SKILL intervention or a business-as-usual instruction. This article reports secondary analyses examining the efficacy of SKILL for bilingual (n = 148) and monolingual (n = 207) students who completed measures of oral and written narrative language and reading comprehension in English. Moderation results showed that the effects of SKILL did not differ for monolinguals and bilinguals across most narrative language measures and did not vary for monolinguals or bilinguals based on their pre-intervention language performance. These findings that suggest a language-based approach to improving narrative production and comprehension yielded similar results for monolinguals and bilinguals and that neither monolinguals nor bilinguals in this study needed to meet a certain threshold of English language proficiency to benefit from the intervention.


Early nutrition and leptin concentrations in later life.
Formula feeding or overweight in infancy may increase the later risk of obesity, but the mechanisms involved are uncertain. Because obesity is associated with high leptin concentrations relative to fat mass, programming of leptin concentrations may be one mechanism by which early nutrition influences later obesity. We tested the hypothesis that high nutrient intake or formula feeding in infancy programs greater leptin concentrations relative to fat mass in later life. Serum leptin concentrations were measured by radioimmunoassay in 197 adolescents aged 13-16 y who were born preterm and randomly assigned at birth to receive either a nutrient-enriched preterm formula or banked donated breast milk (trial 1) or a preterm formula or a standard formula (trial 2). Fat mass was estimated with the use of bioelectrical impedance analysis. After combining the results of trials 1 and 2 as planned, the ratio of leptin to fat mass was significantly greater in the children who received the preterm formula (geometric : 0.84 microg x L(-1) x kg(-1)) than in those who received standard formula or banked breast milk (0.62 microg x L(-1) x kg(-1); mean difference: 30.8%; 95% CI for difference: 8.4%, 53.2%; P = 0.007). The difference between the diet groups remained significant after adjustment for age, sex, Tanner stage, social class, and fat mass. Human milk intake was significantly associated with lower leptin concentrations relative to fat mass in adolescence (P = 0.023), independent of potential confounding factors. Programming of relative leptin concentrations by early diet may be one mechanism that links early nutrition with later obesity.


Clinical experience of electroconvulsive therapy with anaesthetic and muscle relaxant at the Clínica Universidad de La Sabana: 2009-2017.
Electroconvulsive therapy is an effective and safe procedure, which is indicated mainly in patients with both unipolar and bipolar depressive episodes, mania and schizophrenia, when they do not respond to other treatments. To describe the demographic, social and clinical properties of a group of patients treated with electroconvulsive therapy (ECT) with anaesthetic and muscular relaxant at the Universidad de La Sabana Clinic for a period of 8 years. The databases and records of the procedures were reviewed from 1 January 2009 to 31 December 2017. An analysis was performed with descriptive statistics. In this period, 1322 procedures were performed on 143 patients (54.5% women) with an associated diagnosis of major depression in 57%. The number of treatments per person was 9.2 and complications occurred in 3.8%, without any of them requiring invasive management. Electroconvulsive therapy is performed safely in patients and with different parameters in terms of age, gender and diagnosis, in comparison to other countries in Latin America and the world. It is important to join efforts in research that allow a more complete overview of the characteristics of its application in the country.


Adoptive immunotherapy of HCMV infection.
Human cytomegalovirus (HCMV) infection or reactivation is a frequent cause of morbidity and mortality in immunocompromised individuals such as transplant recipients. Primary HCMV infection or reactivation of HCMV from latency is mostly asymptomatic in immunocompetent individuals and is controlled by the host's cell-mediated immune response. Healthy HCMV seropositive individuals develop high frequencies of HCMV-specific cytotoxic T lymphocytes (CTL) in the peripheral blood. Furthermore, a direct correlation between the recovery of HCMV-specific CTL responses and an improved outcome of HCMV disease could be demonstrated in immunocompromised patients. Deriving from these observations, the strategy of an adoptive transfer of HCMV-specific T cells has been developed. Protective immunity can be transferred successfully by the infusion of donor-derived HCMV-specific CD8+ cytotoxic T-cell clones or cell lines. In addition, several studies have supported the importance of antiviral effector functions of Th cells in maintaining CTL responses after adoptive transfer and their capacity to produce antiviral cytokines. Until today, a broad variety of clinical protocols for HCMV-specific immunotherapy has been published. These protocols vary regarding the isolation procedure, composition of cellular product, number of transferred cells and thus treatment efficacy. In this review, we aim to provide a comprehensive synopsis of the current standard of knowledge concerning cellular HCMV-specific immunotherapeutic approaches.


[The treatment of the phantom pain syndrome with tizanidine].
The authors carried out estimation of analgetic effect of tisanidin by double blind test in patients with phantom limb pain syndrome. 14 patients took the medicine in a dose of 12 mg/day and 5 patients took placebo at the same dose. Characteristics and intensity of pain were estimated in accordance with McGill pain questionnaire and visual analogue scale. Pain possessed more than one sensory characteristics in the majority of patients. Tisanidin had a significant analgetic influence on all type of phantom limb pain: "neuralgic"--acute, shooting, transitory, "causalgic"--hot, burning, searing, "cramping" pain. Pain sensation did not decrease only in one of 14 patients treated with tisanidin. The authors explain the effectivity of the drug for treatment of phantom limb pain of different sensory modality by variety of the mechanisms of its therapeutic action, the capacity to decrease the releasing of excitatory neurotransmitter amino acids and the influence on alpha 2-adrenoceptors.


The Language of Love?-Verbal versus Implied Consent at First Heterosexual Intercourse: Implications for Contraceptive Use.
Little is known about how young people communicate about initiating intercourse. This study was designed to gauge the prevalence of implied versus verbal consent at first intercourse in a U.S. college population, assess effects of consent type on contraceptive use, and explore the influences of gender, race and other factors. We conducted and analyzed a cross-sectional survey of non-Hispanic white and black students from four universities, exploring associations between verbal and nonverbal consent, contraceptive use and covariates. Among those with consensual first intercourse experiences (N=1883), half (49%) provided nonverbal consent. Black men were the most likely to provide nonverbal consent (61%), followed by white men (55%), black women (51%), and white women (43%). Respondents who used condoms at first intercourse were more likely to provide verbal consent, suggesting that condoms may prompt sexual discussions (or vice versa). In contrast, even when controlling for covariates, those who provided nonverbal consent were less likely to have used contraception (significantly so for women). These findings confirm the hypothesis that young people who do not discuss whether to engage in vaginal intercourse for the first time are less likely to use contraception. These results add an important layer to our current conceptual model of sexual development, in particular, how young people adopt, or fail to adopt, behaviors that will keep them healthy once they decide to become sexually active. Enhanced sexual communication skills are greatly needed. Public health practitioners should investigate type of consent in future research and programming, with sensitivity to gender and racial influences.


Management of fetal ductus arteriosus constriction with Digoxin and oxygen therapy.
Constriction of the fetal ductus arteriosus is rare and usually attributed to medications or CHD. We describe a 24-year-old multigravida at 33 weeks 5 days gestation with echocardiographic findings of severe ductal constriction, a dilated, hypertrophied and hypocontractile right ventricle, and severe tricuspid regurgitation following BC powder® use. Treatment with Digoxin and oxygen resulted in a progressive 71% reduction in peak systolic ductal gradient, improved right ventricular function, and decreased tricuspid regurgitation.


Simpson-Golabi-Behmel syndrome with 46,XY disorders of sex development: A case report.
We present a case of a Chinese child with X-linked Simpson-Golabi-Behmel syndrome (SGBS). To the best of our knowledge, this is the first report of 46,XY disorders of sex development (ambiguous genitalia, cryptorchidism, and uterus in the pelvis) in surviving SGBS patients. Other external anomalies included characteristic facial anomalies, overgrowth, macrocephaly, organomegaly, pectus excavatum, and cryptorchidism. It could be that the GPC3 gene mutation caused Leydig cell dysfunction in our patient. Disorders of sex development can be included as part of the clinical spectrum of SGBS.


Human papillomavirus and Chlamydia trachomatis infection in gyneco-obstetric outpatients from a mexican hospital.
Human papillomavirus (HPV) and Chlamydia trachomatis are the most frequent sexually transmitted infections, usually asymptomatic. Persistent infection with high-risk HPV types and other cofactors such as the concomitant infection with C. trachomatis can represent a higher risk to develop cervical lesions; therefore, screening with sensitive methods could aid to identify women at risk. The aim is to determine the prevalence and concurrence of both infections, detected with in-house molecular methods, and to identify the risk factors associated to the infections in Mexican women. This was a cross-sectional study including gynaecological-obstetrical medical outpatients from a Social Security Hospital in Southeast Mexico. After informed consent, cervicovaginal samples were collected and tested for HPV and C. trachomatis using polymerase chain reaction (PCR). HPV positives were further tested for high-risk HPV16, 18, 58 and low-risk 11 using real-time PCR. All methods employed were in-house. Data analyses included odds ratios (OR), Chi-square and linear regressions. Women included were 233, aging 15-49 (mean 30 years), 52.8% were pregnant. For HPV and C. trachomatis testing, 230 samples were adequate, resulting in 48 (20.9%) and 15 (6.5%) positives, respectively; 4 (1.7%) were positive to both. The most frequent genotype identified was HPV58 (25% of typified samples). C. trachomatis positives were 73% asymptomatic, none had pelvic inflammatory disease or infertility histories. The only variable associated to HPV infection was the history of previous sexually transmitted disease (OR = 3.69,P= 0.0019). More than 25% of the population was infected with either agent. We successfully used in-house molecular methodologies for diagnosis and typing, showing HPV and C. trachomatis prevalence consistent to previous reports. Concomitant infections were found, HPV high-risk types were involved in half of these cases, representing a higher risk.


[Genetic diversity of extraintestinal Escherichia coli strains producers of beta-lactamases TEM, SHV and CTX-M associated with healthcare].
There are few reports from Venezuela describing the genetic basis that sustains the pathogenic potential and phylogenetics of Escherichia coli extraintestinal strains isolated in health care units. To establish the genetic diversity of extraintestinal E. coli strains producers of betalactamases TEM, SHV and CTX-M associated with healthcare. We studied a collection of 12 strains of extraintestinal E. coli with diminished sensitivity to broad-spectrum cephalosporins. Antimicrobial susceptibility was determined by minimum inhibitory concentration. We determined the phylogenetic groups, virulence factors and genes encoding antimicrobial resistance using PCR, and clonal characterization by repetitive element palindromic-PCR rep-PCR. All strains showed resistance to cephalosporins and joint resistance to quinolones and aminoglycosides. The phylogenetic distribution showed that the A and B1 groups were the most frequent, followed by D and B2. We found all the virulence factors analyzed in the B2 group, and fimH gene was the most frequent among them. We found blaCTX-M in all strains,with a higher prevalence of blaCTX-M-8; two of these strains showed coproduction of blaCTX-M-9 and were genetically identified as blaCTXM-65 and blaCTX-M-147 by sequencing. The strains under study showed genetic diversity, hosting a variety of virulence genes, as well as antimicrobial resistance with no particular phylogroup prevalence. This is the first report of blaCTX-M alleles in Venezuela and in the world associated to non-genetically related strains isolated in health care units, a situation that deserves attention, as well as the rationalization of antimicrobials use.


Platelet-activating factor and platelet-activating factor antagonists in acute pancreatitis.
Acute pancreatitis causes platelet-activating factor (PAF) to be released which induces systemic effects that contribute to circulatory disturbances and multiple organ failure. PAF has also been implicated as a key mediator in the progression of severe acute pancreatitis, which can lead to complications and unacceptably high mortality rates. Synthesis of PAF is sensitive to biologically active mediators seen in many inflammatory processes. PAF significantly potentiates pancreatic tissue damage; it causes serum amylase and lipase levels to rise significantly, causes scattered haemorrhages and may serve as a primary mediator of inflammation. Several classes of compounds show significant PAF antagonisms, and all have shown significant local and systemic effects to reduce inflammatory changes. Only lexipafant, however, has been studied in human acute pancreatitis. Lexipafant specifically binds to the PAF receptor and is more potent than other PAF antagonists. In clinical trials lexipafant reduces organ failure and suppresses some aspects of the inflammatory response. Our understanding of the pathology of systemic complications, and of a central role of PAF in mediating an inappropriate inflammatory response has improved in recent years. Confirmation of clinical findings with lexipafant will indicate an effective new therapy for the treatment of severe acute pancreatitis.


Mobile health applications for mental illnesses: An Asian context.
Advances in digital technologies have created unprecedented opportunities to assess and improve health behavior and health outcomes. Evidence indicates that a majority of the world's population, including traditionally underserved populations and low- and middle-income countries, has access to mobile technologies (phones, tablets, mobile devices). Given the widespread access to mobile technology worldwide, health behavior-change tools delivered on mobile platforms enable broader reach and scalability of evidence-based assessment and interventions, especially for addressing the growing burden of mental health disorders globally. The purpose of this article was to present a qualitative review of mobile mental health applications in an Asian context. We searched on-line databases and included 22 articles in this review. We have identified mobile health applications that address eight categories of mental illnesses. These applications were developed in only six countries and regions in Asia. Future studies from more diverse countries for diverse cultures should be conducted to examine the advantages and disadvantages of mobile health technology.


Efficient recombinant production of prodigiosin in Pseudomonas putida.
Serratia marcescens and several other bacteria produce the red-colored pigment prodigiosin which possesses bioactivities as an antimicrobial, anticancer, and immunosuppressive agent. Therefore, there is a great interest to produce this natural compound. Efforts aiming at its biotechnological production have so far largely focused on the original producer and opportunistic human pathogen S. marcescens. Here, we demonstrate efficient prodigiosin production in the heterologous host Pseudomonas putida. Random chromosomal integration of the 21 kb prodigiosin biosynthesis gene cluster of S. marcescens in P. putida KT2440 was employed to construct constitutive prodigiosin production strains. Standard cultivation parameters were optimized such that titers of 94 mg/L culture were obtained upon growth of P. putida at 20°C using rich medium under high aeration conditions. Subsequently, a novel, fast and effective protocol for prodigiosin extraction and purification was established enabling the straightforward isolation of prodigiosin from P. putida growth medium. In summary, we describe here a highly efficient method for the heterologous biosynthetic production of prodigiosin which may serve as a basis to produce large amounts of this bioactive natural compound and may provide a platform for further in-depth studies of prodiginine biosynthesis.


Constant compression decreases vascular bud and VEGFA expression in a rabbit vertebral endplate ex vivo culture model.
The vascular buds in the vertebral endplate (VEP) are the structural foundation of nutrient exchange in the intervertebral disc (IVD). VEGF is closely related to angiogenesis in the endplate and intervertebral disc degeneration (IDD). To investigate the effects of static load on vascular buds and VEGF expression in the VEP and to further clarify the relation between IDD and VEGF. IVD motion segments were harvested from rabbit lumbar spines and cultured under no-loading conditions (controls) or in custom-made apparatuses under a constant compressive load (0.5 MPa) for up to 14 days. Tissue integrity and the number of vascular buds were determined, and the concentrations and expression of Aggrecan, COL2a1, and VEGFA in the VEPs were assessed after 3, 7, and 14 days of culturing and then compared with those of fresh tissues. Under the constant compression, the morphological integrity of the VEPs was gradually disrupted, and immunohistochemistry results showed a significant decrease in the levels of Agg and COL2a1. During the static load, the number of vascular buds in the VEPs was gradually reduced from the early stage of culture, and ELISA showed that the constant compressive load caused a significant decrease in the VEGFA and VEGFR2 protein concentrations, which were consistent with the immunohistochemistry results. Western blot and RT-PCR results also showed that the loading state caused a significant decrease in VEGFA expression compared with that of fresh and control samples. Constant compression caused degeneration of the VEP as well as a decreased number of vascular buds, thereby accelerating disc degeneration. VEGFA is involved in this process. We anticipate that regulating the expression of VEGFA may improve the condition of the lesions to the vascular buds in the endplates, thus enhancing the nutritional supply function in IVD and providing new therapeutic targets and strategies for the effective prevention and treatment of IDD.


Development and review of the voluntary phase of a national BVD eradication programme in Ireland.
The voluntary phase of an industry-led national Bovine Viral Diarrhoea (BVD) eradication programme began in Ireland on January 1, 2012 with the goal of progressing to a compulsory programme in 2013. The development and implementation of the programme in 2012 was informed by a review of current and prior eradication programmes elsewhere in Europe and extensive stakeholder consultation. The programme was based on tissue tag testing of newborn calves in participating herds, with the status of the mothers of calves with positive or inconclusive results requiring clarification. Participating herd owners were required to comply with a series of guidelines, including not selling cattle suspected of being persistently infected. For herds compliant with the guidelines, the results from 2012 counted as one of three years of tag testing anticipated in the compulsory phase of the programme. Testing was carried out in laboratories designated for this purpose by the cross-industry BVD Implementation Group that oversees the programme. Results were reported to a central database managed by the Irish Cattle Breeding Federation, and the majority of results were reported to farmers' mobile telephones by SMS message. A detailed review of the programme was conducted, encompassing the period between January 1, 2012 and July 15, 2012, based on results from approximately 500,000 calves. This paper describes the establishment and structure of the programme, and the outcomes of the review, including findings at herd and animal level.


Extremely wideband low-RCS polarization conversion metasurface based on multivariate phase destructive interference.
In this paper, a polarization modulated metasurface to improve the magnitude and expand the bandwidth of radar cross section (RCS) reduction is presented. Two physical mechanisms are responsible for the reflection diffusion of the proposed metasurface. One is the functionality of controlling the spatial distribution of polarization response, and the other is the capability of spanning the entire 2π phase range by making full use of the variable sizes and height difference of unit cells to achieve superwideband phase cancellation. A 10 dB monostatic RCS reduction is obtained from 3.87 to 92.89 GHz (a ratio bandwidth of 24:1) for both polarizations under normal incidence by simulation, which is identical to experimental results and theoretical analysis. The proposed method for suppressing vector fields in an extremely wide band may hold promising potentials for suppression of acoustic, electromagnetic, optical and other elastic waves.


Formoterol added to low-dose budesonide has no additional antiinflammatory effect in asthmatic patients.
Adding inhaled long-acting beta2-agonists to a low dose of inhaled corticosteroids (ICSs) results in better asthma control than increasing the dose of ICSs. An important, but as yet unresolved, question is whether this is due to an additional reduction of airway inflammation. Double-blind, parallel-group trial. Forty asthma patients (FEV1, 50 to 90% predicted; provocative concentration of a substance [methacholine] causing a 20% fall in FEV1 of < 8 mg/mL; no ICSs in the last 4 weeks). Randomization to 8 weeks of treatment with 100 microg of budesonide bid plus placebo (BUD200) or 100 microg of budesonide bid plus 12 microg of formoterol (BUD200 + F). Then the dose of budesonide (BUD) was increased to 400 microg bid in both groups for another 8 weeks. Bronchial biopsy specimens were collected before, and after 8 and 16 weeks of treatment. Eosinophils (major basic protein [MBP]) and mast cells (tryptase) were analyzed by immunohistochemistry. BUD200 reduced the MBP staining (p = 0.008) and tryptase staining (p = 0.048) in the epithelium compared to baseline levels. There were no significant differences between the BUD200 and BUD200 + F groups. In both groups, increasing the dosage of BUD to 800 microg had no significant additional antiinflammatory effect. Our results demonstrate that BUD administered at a low dose has significant antiinflammatory effects in patients with mild asthma. No significant additional antiinflammatory effects could be demonstrated either by adding formoterol or by increasing the dose of BUD.


SPECT study of cerebral blood flow reactivity after acetazolamide in patients with transient ischemic attacks.
We investigated 15 patients with one or more transient ischemic attacks (TIAs) in the internal carotid artery territory within the month following the most recent TIA. Cerebral blood flow (CBF) was measured by single-photon emission computed tomography, using intravenous xenon-133 before and after injection of 1 g acetazolamide. Six patients had severe carotid stenosis or occlusion; the other nine patients had no significant carotid lesions. Twenty age-matched volunteers free of neurologic symptoms or history were used as controls. Mean CBF in the sylvian region was not significantly different between patients and controls. Seven patients exhibited a focal hypoperfusion at rest in the symptomatic hemisphere, and their hypoperfused areas were hyporeactive after administration of acetazolamide. Seven other patients exhibited hyporeactive areas after acetazolamide administration while their CBF tomograms at rest were normal. Thus, CBF abnormalities were detected in 14 of the 15 patients. Our findings suggest that CBF measured early after acetazolamide administration could be useful to confirm the clinical diagnosis of TIA. In the nine patients with no significant lesion of the internal carotid artery, the areas of hypoperfusion were small and were probably related to the focal ischemic event. In the six patients with severe lesions of the internal carotid artery, abnormalities were of variable size and intensity but were often large and pronounced. The discrepancy between these two subgroups of patients could be ascribed to the hemodynamic influence of the internal carotid artery lesions. Moreover, our findings may provide some insight into the pathophysiology of TIAs.


[Risk factor analysis of lymph node metastasis in endometrial carcinoma combined with molecular types].
Objective: To investigate the relationships between molecular types of the cancer genome atlas (TCGA) of patients with endometrial carcinoma (EC) and lymph node metastasis and other clinicopathological features. Methods: The clinical pathological information of 295 patients with EC who underwent initial inpatient surgical treatment and accepted the detection of the molecular types of TCGA with next-generation sequencing technology at Peking University People's Hospital were collected during April 2016 and May 2022. The TCGA molecular typing of EC was divided into four types: POLE-ultramutated (15 cases), high microsatellite instability (MSI-H; 50 cases), copy-number low (CNL; 175 cases), and copy-number high (CNH; 55 cases). The differences of clinical pathological features among different molecular types and the risk factors of lymph node metastasis were analyzed retrospectively. Results: Among 295 patients with EC, the average age was (56.9±0.6) years. (1) There was a statistically significant difference in lymph node metastasis (0, 8.0%, 10.3% and 25.5%) among the four molecular types (χ2=12.524, P=0.006). There were significant differences in age, stage, pathological type, grade (only endometrioid carcinoma), myometrium invasion, lymphatic vascular space infiltration, and estrogen receptor among the EC patients of four molecular types (all P<0.05). Among them, while in the patients with CNH type, the pathological grade was G3, the pathological type was non-endometrioid carcinoma, and the proportion of myographic infiltration depth ≥1/2 were higher (all P<0.05). (2) Univariate analysis suggested that pathological type, grade, myometrium infiltration depth, cervical interstitial infiltration, lymphatic vascular space infiltration, and progesterone receptor were all factors which significantly influence lymph node metastasis (all P<0.01); multivariate analysis suggested that the lymphatic vascular space infiltration was an independent risk factor for lymph node metastasis (OR=5.884, 95%CI: 1.633-21.211; P=0.007). (3) The factors related to lymph node metastasis were different in patients with different molecular types. In the patients with MSI-H, the non-endometrioid carcinoma of pathological type was independent risk factor for lymph node metastasis (OR=29.010, 95%CI: 2.067-407.173; P=0.012). In the patients with CNL, myometrium infiltration depth≥1/2 (OR=4.995, 95%CI: 1.225-20.376; P=0.025), lymphatic vascular space infiltration (OR=14.577, 95%CI: 3.603-58.968; P<0.001) were the independent risk factors for lymph node metastasis. While in the CNH type patients pathological type of non-endometrioid carcinoma (OR=7.451, 95%CI: 1.127-49.281; P=0.037), cervical interstitial infiltration (OR=22.938, 95%CI: 1.207-436.012; P=0.037), lymphatic vascular space infiltration (OR=9.404, 95%CI: 1.609-54.969; P=0.013), were the independent risk factors for lymph node metastasis. Conclusions: POLE-ultramutated EC patients have the lowest risk of lymph node metastasis, and CNH patients have the highest risk of lymph node metastasis. The risk factors of lymph node metastasis of different molecular types are different. According to preoperative pathological and imaging data, lymph node metastasis is more likely to occur in patients with non-endometrioid carcinoma in MSI-H and CNH type patients, and lymph node metastasis is more likely to occur in patients with myometrium infiltration depth ≥1/2 in CNL type patients.


Transposon mutagenesis identifies cooperating genetic drivers during keratinocyte transformation and cutaneous squamous cell carcinoma progression.
The systematic identification of genetic events driving cellular transformation and tumor progression in the absence of a highly recurrent oncogenic driver mutation is a challenge in cutaneous oncology. In cutaneous squamous cell carcinoma (cuSCC), the high UV-induced mutational burden poses a hurdle to achieve a complete molecular landscape of this disease. Here, we utilized the Sleeping Beauty transposon mutagenesis system to statistically define drivers of keratinocyte transformation and cuSCC progression in vivo in the absence of UV-IR, and identified both known tumor suppressor genes and novel oncogenic drivers of cuSCC. Functional analysis confirms an oncogenic role for the ZMIZ genes, and tumor suppressive roles for KMT2C, CREBBP and NCOA2, in the initiation or progression of human cuSCC. Taken together, our in vivo screen demonstrates an extremely heterogeneous genetic landscape of cuSCC initiation and progression, which can be harnessed to better understand skin oncogenic etiology and prioritize therapeutic candidates.


A three-dimensional skin equivalent reflecting some aspects of in vivo aged skin.
Human skin undergoes morphological, biochemical and functional modifications during the ageing process. This study was designed to produce a 3-dimensional (3D) skin equivalent in vitro reflecting some aspects of in vivo aged skin. Reconstructed skin was generated by co-culturing skin fibroblasts and keratinocytes on a collagen-glycosaminoglycan-chitosan scaffold, and ageing was induced by the exposition of fibroblasts to Mitomycin-C (MMC). Recently published data showed that MMC treatment resulted in a drug-induced accelerated senescence (DIAS) in human dermal fibroblast cultures. Next to established ageing markers, histological changes were analysed in comparison with in vivo aged skin. In aged epidermis, the filaggrin expression is reduced in vivo and in vitro. Furthermore, in dermal tissue, the amount of elastin and collagen is lowered in aged skin in vivo as well as after the treatment of 3D skin equivalents with MMC in vitro. Our results show histological signs and some aspects of ageing in a 3D skin equivalent in vitro, which mimics aged skin in vivo.


Putting the humanities back into medicine: some suggestions.
The practice of medicine is an art as well as a science. As doctors diagnose illness and treat patients day after day, they constantly interweave the social, psychological, ethical and scientific aspects of clinical practice. However, the humanistic values necessary for this approach are generally perceived to be lacking in today's medical practice. The Medical Council of India (MCI) believes that a course in medical humanities can help students cultivate a humane attitude towards their patients, as well as give them the knowledge and skills to deal with the complex challenges they will face as they practise medicine. The new Graduate Medical Regulations being formulated by the MCI provide time for teaching this aspect of medical practice. This paper contains some suggestions for the implementation of a medical humanities course in medical colleges.


Internal consistency and stability of the CANTAB neuropsychological test battery in children.
The Cambridge Neuropsychological Test Automated Battery (CANTAB) is a computer-assessed test battery widely use in different populations. The internal consistency and 1-year stability of CANTAB tests were examined in school-age children. Two hundred-thirty children (57% girls) from five schools in the Jyväskylä school district in Finland participated in the study in spring 2011. The children completed the following CANTAB tests: (a) visual memory (pattern recognition memory [PRM] and spatial recognition memory [SRM]), (b) executive function (spatial span [SSP], Stockings of Cambridge [SOC], and intra-extra dimensional set shift [IED]), and (c) attention (reaction time [RTI] and rapid visual information processing [RVP]). Seventy-four children participated in the follow-up measurements (64% girls) in spring 2012. Cronbach's alpha reliability coefficient was used to estimate the internal consistency of the nonhampering test, and structural equation models were applied to examine the stability of these tests. The reliability and the stability could not be determined for IED or SSP because of the nature of these tests. The internal consistency was acceptable only in the RTI task. The 1-year stability was moderate-to-good for the PRM, RTI, and RVP. The SSP and IED showed a moderate correlation between the two measurement points. The SRM and the SOC tasks were not reliable or stable measures in this study population. For research purposes, we recommend using structural equation modeling to improve reliability. The results suggest that the reliability and the stability of computer-based test batteries should be confirmed in the target population before using them for clinical or research purposes.


Clinical and Biomechanical Performance of Occlusal Veneers: A Scoping Review.
This manuscript aims to evaluate, through a scoping review, current knowledge of the biomechanical behavior, materials, preparations, and limitations of occlusal veneers. Occlusal veneers are a minimally invasive alternative for the additive restoration of posterior teeth with significant loss of the occlusal structure. This type of restoration has been emerged in recent years as an alternative to invasive treatment, which in the same way seeks to restore the structure of the posterior teeth. All this is because in recent years restorative dentistry has focused a large part of its objectives on conservative therapies. Five electronic databases-PubMed, Cochrane, LILACS, EMBASE, and Google Scholar-were searched. Title and abstracts were independently screened by three reviewers, followed by a full-text review. A total of 42 articles met our inclusion criteria; most of these studies were in vitro (n = 35) and other studies were clinical studies (n = 7). These in vitro studies included 21 studies that analyzed the type of preparation and 6 studies that evaluated the limitations of occlusal veneers. Thicknesses between 0.7 and 1.0 mm are recommended for ceramic materials; in addition, thicknesses less than 0.7 mm are recommended to use polymeric materials. The materials used for this type of restoration are plastic- and ceramic-based materials, whose load resistance values were found to exceed 2000 N in most studies. It is recommended to carry out a minimally invasive preparation or not to carry out a dental preparation, as long as there is a peripheral enamel to make an external bevel that redirects the eccentric forces to the axis of the tooth. Restorative dentistry has moved toward conservative treatments with the least amount of dental tissue being removed. Occlusal veneers appear to be a conservative option in the reconstruction of tooth tissues lost due to tooth wear and in cases where it is necessary to restore or increase the vertical dimension.


Focal Biliary System Obstruction and Atypical Liver Mass: Intrabiliary Ruptured Cyst Hydatid Case Report.
Hydatid disease can involve any part of the body, but the liver is the most frequently affected organ. Intrabiliary rupture is one of the most serious complications of a hepatic hydatid cyst. Radiological findings, especially magnetic resonance imaging and magnetic resonance cholangiopancreatography (MRI/MRCP), are helpful in the diagnosis of hydatid disease. We present a 48-year-old female patient with complaints of abdominal pain and jaundice. Radiological examination showed a heterogeneous lesion that contained cystic-solid components and millimetric calcifications in the liver. Adjacent intrahepatic bile ducts were dilated. In geographical areas endemic for hydatid disease, cyst rapture into the bile ducts should be included in the differential diagnosis even in seronegative cases, although it is not typical for hydatid cyst to be found as a mass lesion in the liver on US in patients with right upper quadrant pain and jaundice.Detailed imaging by MRI/MRCP should be done.


Odd-Electron Bonds.
The history and theory of one- and three-electron bonds are presented and discussed. It is shown that the dependence of the odd-electron bond energy on the difference in ionization potentials of the bonding partners must be corrected to include the ion-pairing energy for neutral odd-electron bonded complexes.


Detection of Tip Fold-Over of the Slim Modiolar Electrode Using Intraoperative Mobile Cone-Beam Computed Tomography.
This study aimed to evaluate the importance of mobile cone-beam computed tomography in detecting tip fold-over of a slim modiolar electrode within the cochlea during surgery. Retrospective case review. Tertiary medical center. From January 2020 to June 2022, 33 ears of 30 patients with normal cochlear morphology underwent cochlear implantation with slim modiolar electrodes and intraoperative mobile cone-beam computed tomography imaging. Furthermore, we retrospectively reviewed the medical records and images. The tip fold-over of the electrodes was detected using mobile cone-beam computed tomography in 3 out of 33 ears (9.1%). We could not identify the tip fold-over by scouting plain X-ray images in 2 out of 3 cases before taking the cone-beam computed tomography images. Electrode removal and reinsertion were performed before wound closure and the successful reinsertion was confirmed by mobile cone-beam computed tomography. The folded electrode tips were located at 238.8°, 152°, and 185.8°. Intraoperative mobile cone-beam computed tomography is useful in detecting the tip fold-over of the slim modiolar electrodes during surgery. Therefore, it was possible to reinsert the electrodes in all cases before closing the wound, eliminating the need for revision surgeries. Moreover, the analysis of mobile cone-beam computed tomography images may help to elucidate the mechanisms of electrode tip fold-over.


Characterization, antibacterial activity and antibiotic modifying action of the Caryocar coriaceum Wittm. pulp and almond fixed oil.
In this study the physicochemical characterization of the pulp and almond fixed oil was carried out; their antibacterial activity and aminoglycoside antibiotic modifying action against standard and multiresistant Gram-positive and -negative bacteria were investigated using the broth microdilution assay. Physical properties such as moisture, pH, acidity, peroxide index, relative density and refractive index indicate stability and chemical quality of the oils. In the GC/MS chemical composition analysis, a high unsaturated fatty acid content and the presence of oleic and palmitic acids were observed in the oils. In the antibacterial assay, more significant results were obtained for Escherichia coli, while other standard and multi-resistant strains presented MIC values ≥ 1024 μg/mL. Furthermore, the fixed oils in association with antibiotics were able to significantly improve antibacterial activity against S. aureus with a reduction in MICs.


Palmoplantar lichen planus.
Palmoplantar lichen planus (PPLP) is an uncommon variant of lichen planus that affects the palms and soles. Clinical findings are varied although they have been conceptualized into two large groupings, an erythematous scaly pattern and a hyperkeratotic pattern. Histopathologic features are those of classic LP. We present a case of PPLP that improved with methotrexate after failing treatment with acitretin.


Ischemic stroke in young HIV-positive patients in Kwazulu-Natal, South Africa.
Cerebrovascular disease occurs in HIV-positive individuals, but no relationship between the two has been established. The authors reviewed a cohort of patients aged 15 to 44 years to evaluate stroke in HIV-positive and negative subjects. Patients who were HIV-positive with no other identifiable etiology were compared to age- and race-matched HIV-negative patients. HIV-positive and HIV-negative groups did not differ in angiographic, cardiac, or serologic tests. A positive HIV test does not provide causal information or diagnosis.


Excess Body Mass Index Loss at 3 Months: A Predictive Factor of Long-Term Result after Sleeve Gastrectomy.
Introduction. Laparoscopic Sleeve Gastrectomy (SG) is considered as successful if the percentage of Excess Body Mass Index Loss (% EBMIL) remains constant over 50% with long-term follow-up. The aim of this study was to evaluate whether early % EBMIL was predictive of success after SG. Methods. This retrospective study included patients who had SG with two years of follow-up. Patients had follow-up appointments at 3 (M3), 6, 12, and 24 months (M24). Data as weight and Body Mass Index (BMI) were collected systematically. We estimated the % EBMIL necessary to establish a correlation between M3 and M24 compared to % EBMIL speeds and calculated a limit value of % EBMIL predictive of success. Results. Data at operative time, M3, and M24 were available for 128 patients. Pearson test showed a correlation between % EBMIL at M3 and that at M24 (r = 0.74; p < 0.0001). % EBMIL speed between surgery and M3 (p = 0.0011) was significant but not between M3 and M24. A linear regression analysis proved that % EBMIL over 20.1% at M3 (p < 0.0001) predicted a final % EBMIL over 50%. Conclusions. % EBMIL at M3 after SG is correlated with % EBMIL in the long term. % EBMIL speed was significant in the first 3 months. % EBMIL over 20.1% at M3 leads to the success of SG.


Manipulating shear-induced non-equilibrium transitions in colloidal films by feedback control.
Using Brownian Dynamics (BD) simulations we investigate non-equilibrium transitions of sheared colloidal films under controlled shear stress σxz. In our approach the shear rate [small gamma, Greek, dot above] is a dynamical variable, which relaxes on a time scale τc such that the instantaneous, configuration-dependent stress σxz(t) approaches a pre-imposed value. Investigating the dynamics under this "feedback-control" scheme we find unique behavior in regions where the flow curve σxz([small gamma, Greek, dot above]) of the uncontrolled system is monotonic. However, in non-monotonic regions our method allows to select between dynamical states characterized by different in-plane structure and viscosities. Indeed, the final state strongly depends on τc relative to an intrinsic relaxation time of the uncontrolled system. The critical values of τc are estimated on the basis of a simple model.


Anti-Helicobacter pylori potential of artemisinin and its derivatives.
The antimalarial drug artemisinin from Artemisia annua demonstrated remarkably strong activity against Helicobacter pylori, the pathogen responsible for peptic ulcer diseases. In an effort to develop a novel antimicrobial chemotherapeutic agent containing such a sesquiterpene lactone endoperoxide, a series of analogues (2 natural and 15 semisynthetic molecules), including eight newly synthesized compounds, were investigated against clinical and standard strains of H. pylori. The antimicrobial spectrum against 10 H. pylori strains and a few other bacterial and fungal strains indicated specificity against the ulcer causing organism. Of five promising molecules, a newly synthesized ether derivative β-artecyclopropylmether was found to be the most potent compound, which exhibited MIC range, MIC(90), and minimum bactericidal concentration range values of 0.25 to 1.0 μg/ml, 1.0 μg/ml, and 1 to 16 μg/ml, respectively, against both resistant and sensitive strains of H. pylori. The molecule demonstrated strong bactericidal kinetics with extensive morphological degeneration, retained functional efficacy at stomach acidic pH unlike clarithromycin, did not elicit drug resistance unlike metronidazole, and imparted sensitivity to resistant strains. It is not cytotoxic and exhibits in vivo potentiality to reduce the H. pylori burden in a chronic infection model. Thus, β-artecyclopropylmether could be a lead candidate for anti-H. pylori therapeutics. Since the recurrence of gastroduodenal ulcers is believed to be mainly due to antibiotic resistance of the commensal organism H. pylori, development of a candidate drug from this finding is warranted.


How patients with stroke adjust their step length to step over obstacles.
Step adjustment under temporal constraint is compromised following stroke. However, how step adjustment occurs under no temporal constraint remains unclear. The aim of this study was to investigate how patients with stroke adjust their step length to step over obstacles under no temporal constraint. Twelve patients with stroke and 12 age-matched and sex-matched individuals without stroke participated in an experiment involving the task of stepping over obstacles. Each participant's steps were measured by a footprint method and classified as a long-step, short-step, or even-step strategy. The differences in step length adjustment between patients with and without stroke were analyzed. Stroke survivors adjusted their step length in different ways depending on whether they led with the affected or the unaffected limb. If patients with stroke stepped over the obstacle by leading with the affected limb, they chose the short-step strategy. This strategy is probably intended to enhance accuracy and maintain stability. In conclusion, patients with stroke utilize a different step adjustment strategy to individuals without stroke, even in the absence of temporal constraint.


Overexpression of decorin promoted angiogenesis in diabetic cardiomyopathy via IGF1R-AKT-VEGF signaling.
Microcirculatory dysfunction is believed to play an important role in diabetic cardiomyopathy. The small leucine-rich proteoglycan decorin is generally considered a pro-angiogenic factor. Here, we investigate whether overexpression of decorin ameliorates diabetic cardiomyopathy and its effects on angiogenesis in vivo and in vitro. Diabetes was induced through intraperitoneal injection with streptozotocin combined with a high-fat diet, and decorin was overexpressed via recombinant adeno-associated virus in Wistar rats. Six months later, cardiac function was determined using an echocardiography and cardiac catheter system. The results showed that cardiac function was decreased in diabetic rats and restored by overexpression of decorin. In addition, overexpression of decorin upregulated the expression of VEGF and attenuated the reduction in the cardiac capillary density. In the in vitro study, high glucose induced apoptosis and inhibited the capabilities of tube formation, migration and proliferation, which were all ameliorated by decorin overexpression. Meanwhile, decorin overexpression increased the expression of VEGF and IGF1R, as well as the phosphorylation level of AKT and AP-1. Nonetheless, all of these effects were abolished by pretreatment with the IGF1R antibody or AKT inhibitor. In conclusion, overexpression of decorin ameliorated diabetic cardiomyopathy and promoted angiogenesis through the IGF1R-AKT-VEGF signaling pathway in vivo and in vitro.


Pulsed EPR studies of nonexchangeable protons near the Mo(V) center of sulfite oxidase: direct detection of the alpha-proton of the coordinated cysteinyl residue and structural implications for the active site.
Pulsed electron nuclear double resonance (ENDOR) spectra of nonexchangeable protons in the vicinity of the Mo(V) center of the high pH (hpH) and low pH (lpH) forms of native chicken liver sulfite oxidase (SO) and recombinant human SO have been obtained and analyzed for the first time. The close similarity of the spectra for the chicken and human enzymes indicates that the structures of their molybdenum centers are essentially identical. For lpH SO, the closest nonexchangeable proton is found to be approximately 2.8 A from the Mo atom. To more accurately determine the distance to this proton and facilitate its assignment, the C-band electron spin-echo envelope modulation (ESEEM) spectra of lpH SO were also analyzed. From the obtained distance and comparison with the X-ray structure, this closest nonexchangeable proton is assigned to the alpha-proton of the coordinated conserved cysteinyl residue (Cys185 in chicken, Cys207 in human). The closest Mo...H distance for the nonexchangeable protons of hpH SO is found to be approximately 3.3 A. For the cysteinyl alpha-proton, such an increase in the Mo...H distance only requires a very small change in torsional angles. This study demonstrates that details of the enzyme structural rearrangements with pH can be monitored by ENDOR spectroscopy and suggests that a similar approach may be routinely used to probe the orientation of the coordinated cysteinyl residue in mutant forms of SO that are catalytically compromised.


Positive social behaviours are induced and retained after oxytocin manipulations mimicking endogenous concentrations in a wild mammal.
The neuropeptide hormone oxytocin modulates numerous social and parental behaviours across a wide range of species, including humans. We conducted manipulation experiments on wild grey seals (Halichoerus grypus) to determine whether oxytocin increases proximity-seeking behaviour, which has previously been correlated with endogenous oxytocin concentrations in wild seal populations. Pairs of seals that had never met previously were given intravenous injections of 0.41 µg kg-1 oxytocin or saline and were observed for 1 h post-manipulation. The dose was designed to mimic endogenous oxytocin concentrations during the observation period, and is one of the lowest doses used to manipulate behaviour to date. Seals given oxytocin spent significantly more time in close proximity to each other, confirming that oxytocin causes conspecifics to seek others out and remain close to one another. Aggressive and investigative behaviours also significantly fell after oxytocin manipulations. Despite using a minimal oxytocin dose, pro-social behavioural changes unexpectedly persisted for 2 days despite rapid dose clearance from circulation post-injection. This study verifies that oxytocin promotes individuals staying together, demonstrating how the hormone can form positive feedback loops of oxytocin release following conspecific stimuli, increased motivation to remain in close proximity and additional oxytocin release from stimuli received while in close proximity.


Nutritional status of women and children in Malaysian rural populations.
This study was conducted to investigate the nutritional status of the rural population in Malaysia, especially women and children. A total of 262 women aged 18 and over and 183 children aged 2-6 years were selected using multistage cluster sampling from four locations in rural areas. It was found that the prevalence of malnutrition among children 2-6 years old ranged between 25.5% in the Malays Felda settlement scheme to 80% in the Orang Asli settlement. Malnutrition was associated with worm infestations, bottle feeding and early weaning. More than 30% of Orang Asli women were malnourished compared to less than 15% of Malay Felda settlement women. On the other hand, Malay women in the land settlement scheme had a higher risk of developing overweight and diabetes. Goitre was found among 11.5% of children; however, no cretinism was found. Breast feeding was still a common practice among rural mothers, but inadequate health education tended to reduce the duration of breast feeding and increased early weaning. Upgrading women's status in the rural areas will ultimately improve the nutritional and health status of the children and community as a whole.


Kinetics and pharmacodynamic effects of a novel prodrug of N-methyldopamine at single dose in healthy volunteers.
Kinetics and cardiovascular effects of SIM2055 (CAS 103878-96-2), the 4-O-phosphate of N-methyldopamine (epinine), at single dose by the oral route were studied in 9 healthy adult volunteers (6 women and 3 men) ranging in age from 22 to 39 years. SIM2055 was administered at increasing doses (from 100 to 300 mg). Plasma concentrations of free epinine were not detectable after the 100 mg dose, but were measurable after the 200 mg and 300 mg doses. Pharmacokinetic data suggest that in man SIM2055 is promptly absorbed, quickly hydrolysed to epinine, metabolized to homovanillic acid and 3,4-dihydroxy-phenylacetic acid, conjugated with sulphuric acid and excreted in large amounts into urine. The 24-h urinary recovery of the 3 metabolites considered together, expressed as a percentage of the dose of SIM2055 administered, was 78 +/- 6 with the 100 mg dose, 66 +/- 11 with the 200 mg dose and 55 +/- 6 with the 300 mg dose (mean +/- S. D.). SIM2055 was well tolerated by all subjects. After its administration, the heart rate and the systolic and diastolic blood pressure presented no systemic or clinically significant variations. No substantial changes were observed with the ECG parameters. No subject reported gastric or systemic effects during the period of observation.


A model study of ceria-Pt electrocatalysts: stability, redox properties and hydrogen intercalation.
The electrocatalytic properties of advanced metal-oxide catalysts are often related to a synergistic interplay between multiple active catalyst phases. The structure and chemical nature of these active phases are typically established under reaction conditions, i.e. upon interaction of the catalyst with the electrolyte. Here, we present a fundamental surface science (scanning tunneling microscopy, X-ray photoelectron spectroscopy, and low-energy electron diffraction) and electrochemical (cyclic voltammetry) study of CeO2(111) nanoislands on Pt(111) in blank alkaline electrolyte (0.1 M KOH) in a potential window between -0.05 and 0.9 VRHE. We observe a size- and preparation-dependent behavior. Large ceria nanoislands prepared at high temperatures exhibit stable redox behavior with Ce3+/Ce4+ electrooxidation/reduction limited to the surface only. In contrast, ceria nanoislands, smaller than ∼5 nm prepared at a lower temperature, undergo conversion into a fully hydrated phase with Ce3+/Ce4+ redox transitions, which are extended to the subsurface region. While the formation of adsorbed OH species on Pt depends strongly on the ceria coverage, the formation of adsorbed Hads on Pt is independent of the ceria coverage. We assign this observation to intercalation of Hads at the Pt/ceria interface. The intercalated Hads cannot participate in the hydrogen evolution reaction, resulting in the moderation of this reaction by ceria nanoparticles on Pt.


Extra-esophageal manifestations of gastroesophageal reflux disease: diagnosis and treatment.
Gastroesophageal reflux disease (GERD) is a common disease that is often diagnosed based on typical symptoms of heartburn and regurgitation. In addition to these more classic manifestations, GERD is increasingly associated with extra-esophageal symptoms, including chronic cough, asthma, laryngitis, and dental erosions. Due to the poor sensitivity of endoscopy and pH monitoring, and the poor specificity of laryngoscopy, empiric therapy with proton pump inhibitors (PPIs) is now considered the initial diagnostic step in patients suspected of having GERD-related symptoms. For those who improve with PPIs, GERD is the presumed etiology, but for those who remain unresponsive to such therapy, further diagnostic testing with impedance/pH monitoring may be necessary in order to exclude refractory acid or weakly acid reflux. In those with normal test results despite PPI therapy and continued symptoms, causes other than GERD may be pursued. Recent data suggest that in patients with extra-esophageal symptoms, objective findings of moderate-sized hiatal hernia and moderate reflux on pH testing may predict response to acid suppressive therapy. PPI-unresponsive patients usually have causes other than GERD for their extra-esophageal symptoms and continued PPI therapy in this group is not recommended.


Ecological validity of social interaction tests in rats and mice.
Different rat and mouse models are used in studies of social interactions. Simple behavioral measures, which are commonly used in the laboratory, allow to perform relatively short experiments and to use multiple brain manipulation techniques. However, too much focus on the simplest behavioral models generates a serious risk of reducing ecological validity or even studying phenomena which would never happen outside of the laboratory. In this review, we discuss the suitability of mice and rats as model organisms for studying social behaviors, with focus on social transmission of fear paradigms. First, we briefly introduce the concept of domestication and what impact it had on laboratory rodents. Then, we present two aspects of social behaviors, sociability and dominance, which are crucial for social organization in these species. Finally, we present experimental models used for studying how animals transmit information about danger between each other, and how these models may reflect what happens in the natural environment. We discuss the difficulties that arise from our limited knowledge of rat and mouse ecology, especially their social life. We also explore the subject of balancing ecological validity and controllability in rodent models of social behaviors, the latter being particularly important for studying brain activity. Although it is very challenging, an efficient program for social neuroscience research should, in our opinion, aim at bridging the gap between laboratory and field studies.


Is there an association between fear avoidance beliefs, and pain and disability in patients with orofacial pain?
Numerous psychosocial factors have been shown to contribute to the development and perpetuation of orofacial pain. One well-recognized model for explaining the link between psychosocial factors and chronic pain is the fear avoidance model. To date, this proposed link has not been studied in subjects with orofacial pain. During the initial evaluation of subjects with orofacial pain, we collected data on fear avoidance beliefs using the Fear Avoidance Beliefs Questionnaire, and disability and pain. At between 6 and 8 weeks follow-up, we re-collected these data, as well as data addressing subjects' perceived change in their condition. Data were analyzed using correlation coefficients and linear regression. Fear avoidance beliefs at intake were inversely correlated with intake disability, There were no significant associations between fear avoidance beliefs at initial evaluation or in changes in fear avoidance beliefs during the 6-8 weeks follow-up period; and changes in disability, pain or perceived change in condition at 6-8 weeks follow-up. Of note, fear avoidance beliefs increased over the follow-up period, despite improvements in all outcome measures. There was insufficient evidence to suggest that high levels of fear avoidance beliefs at initial evaluation are associated with higher levels of disability or pain at intake, or with change in disability, pain or perceived change in condition at 6-8 weeks follow-up. Similarly, there was insufficient evidence to suggest that changes in fear avoidance beliefs during treatment are associated with any of these outcome measures.


GSTP1 A>G polymorphism and chemosensitivity of osteosarcoma: A meta-analysis.
The association between GSTP1 A>G polymorphism and chemosensitivity of osteosarcoma is controversial according to previously published studies. We conducted this meta-analysis to further investigate the role of GSTP1 A>G genetic variation in response to chemotherapy resistance in patients with osteosarcoma. Using the electronic databases of Pubmed, Wanfang and CNIK were searched to find the studies related to the GSTP1 A>G polymorphism and chemosensitivity of osteosarcoma. The genotype of AA, AG and GG were extracted from the chemotherapy sensitivity and chemotherapy resistance group. The association between GSTP1 A>G polymorphism and chemosensitivity was calculated by STATA11.0 software. The correlation between GSTP1 A>G polymorphism and chemotherapy response was assessed by odds ratio (OR) and its 95% confidence interval (95%CI). Four studies with 681 cases were finally included in this meta-analysis. The pooled data indicated that there was no significant association between GSTP1 A>G polymorphism and chemosensitivity in patients with osteosarcoma [Homozygous genetic model (GG vs AA): OR=0.53, 95%CI: 0.25-1.12, P=0.10; recessive genetic model (GG vs GA+AA): OR=0.61, 95%CI:0.34-1.11,P=0.11; and dominant genetic model (GG+AG vs AA): OR=0.67, 95%CI:0.42-1.07,P=0.10]. No correlation between GSTP1 A>G polymorphism and chemosensitivity was found according to this present meta-analysis. However, the small number of cases in each included study and significant statistical heterogeneity among the trials means the conclusion should be regarded as conservative.


Structures and biological activities of cycloheptamycins A and B.
The heptadepsipeptide cycloheptamycin A was isolated from the terrestrial Streptomyces sp. Tü 6314. Its constitution was elucidated on the basis of NMR spectroscopic experiments and mass spectrometric analysis. Its stereostructure was investigated by peptide hydrolysis and derivatization and firmly established by X-ray structure analysis. In addition to the parent compound, a new cycloheptamycin analog, cycloheptamycin B, was discovered and structurally assigned using comparative MS/MS experiments and NMR. The biological profile of both compounds was investigated, revealing a selective inhibitory potential of cycloheptamycins against Propionibacterium acnes.


Dielectrophoretic and electrophoretic force analysis of colloidal fullerenes in a nematic liquid-crystal medium.
This research focuses on the electrokinetic motion of fullerenes suspended in liquid crystal host medium, which are investigated in the homogeneously aligned nematic liquid crystal cells driven by in-plane field. We investigated the effect of electrophoretic and dielectrophoretic forces and related parameters of the colloidal fullerenes in liquid crystals. The electrophoretic mobility, zeta potential, and critical voltage have been evaluated. Fullerenes suspended in liquid crystal medium migrated toward the positive electrode, but were pulled back in the opposite direction when the polarity was reversed especially at low frequency range (<5 Hz) . At higher electric field and higher frequency ranges, the net displacement of fullerenes has been observed. We demonstrate that the dielectrophoretic force dominated the motion in the colloidal fullerenes by a proper analysis of different electrophoretic parameters. In addition, the electrodynamics of fullerenes was explained by applying the theory of the dielectrophoresis and Schwarz's formula. We propose a model to estimate the density of fullerenes suspended in liquid crystal medium.


Self-reported seasonal variation in depression at 78 degree north. The Svalbard Study.
To explore and compare the one year prevalence of self-reported depression in two ethnically different populations. A cross-sectional study of each population (1988-89 and 1993). Norwegians living in Longyearbyen, Svalbard, and Russians living in Barentsburg and Pyramiden, Svalbard, both representing the world's two northern most regularly inhabited settlements. 506 Norwegians (327 men and 179 women) and 446 Russians (314 men and 132 women), all 18 years or older, living on Svalbard. Among Russians, the one year prevalence of self-reported depression lasting for at least 2 weeks was 26.8% for men and 44.7% for women. Corresponding figures for the Norwegians were 10.7 and 15.6%. For the period with polar night the figures were 5.5 and 6.7% for Norwegians, and 21.7 and 37.1% for Russian men and women, respectively. Depression was most common in the youngest age-group among Russians and in the oldest age-group among the Norwegians. The one year prevalence of depression was 2-3 times higher among Russians compared to Norwegians living on Svalbard. For the period with polar night, the figures were 4-5 times higher for Russians. As both populations are exposed to the same amount of daylight, seasonal depression may therefor not solely be a matter of lack of daylight. Because the Russian population came from lower latitudes than the Norwegians, we hypothesize that insufficient acclimatization after migration to the north is essential for the understanding of seasonal variation in depression.


Water Consumption during a School Day and Children's Short-Term Cognitive Performance: The CogniDROP Randomized Intervention Trial.
There is still little research examining the relationship between water consumption in school and specific cognitive performance. The aim of this cluster-randomized intervention CogniDROP trial was to investigate the short-term effects of drinking water during the morning on executive functions. The participants were from the 5th and 6th grade of a comprehensive school in Germany (14 classes, n = 250, 61.6% boys). The classes were randomly divided into an intervention group (an education on healthy drinking behavior and a promotion of water consumption) and a control group. A battery of computerized tasks (Switch Task, 2-Back Task, Corsi Block-Tapping Task and Flanker Task) was used to test executive functions. Urine color and thirst were evaluated to check the hydration level. Physical activity over the past 24 h was measured using GT3X ActiGraph. A non-linear relationship was observed between the amount of drinking water and executive performance. Consuming water up to 1000 mL (or up to 50% of Total Water Intake) had benefits during memory tasks. Urine color and number of steps on the study day correlated with water consumed. The results suggest that a water-friendly environment supports school-aged children in adequate water intake resulting in better cognitive performance, especially short-term memory.