[Contribution of nested PCR in the diagnosis of imported malaria in southern Algeria].
The nested PCR was used to estimate its inputs in malaria diagnosis and in the performance of the microscope operators involved in the surveillance of malaria in remote areas of South Algeria. For the period 2010 to 2015, 112 patients (93 febrile and 19 asymptomatic) coming from sub-Saharan Africa were tested for malaria in the hospital of Tamanrasset. One part of the blood taken from fingertip was used for blood smears and the second part was absorbed in filter paper for molecular diagnosis. Overall, the infection was detected by nested PCR in 63 samples versus 53 by direct examination. In addition, 11 mixed infections and 6 positive asymptomatic cases not detected by microscopy were diagnosed by PCR. Moreover, two negative samples in nested PCR were tested positive by direct examination. The molecular tool is more sensitive than the direct examination in detecting infra-microscopic parasitaemia and mixed infections...


Diversity and species composition of arbuscular mycorrhizal fungi across maize fields in the southern part of Belgium.
Arbuscular mycorrhizal fungi (AMF) are key actors among soil microbial inhabitants, forming beneficial associations with most horticultural plants and crops (e.g., maize). For maize, the world most cultivated cereal, data on AMF species diversity in fields is sparse and even totally nonexistent in the southern part of Belgium where maize represents 8% of the cultivated area. In the present study, 14 maize fields in South Belgium under conventional, conversion, or organic management were analyzed for AMF diversity and species composition using 454 pyrosequencing. A large part (54%) of the 49 AMF species observed were unknown or have not been described in the literature. AMF diversity highly varied among fields, with the number of species ranging between 1 and 37 according to the field. A statistically significant effect of management was measured on AMF diversity, with the highest Hill index values (diversity and richness) under the organic management system compared with conventional management or conversion. Our results suggest a positive effects of organic management on AMF diversity in maize. They also highlight the rather high diversity or richness of AMF and the large portion of sequences not yet ascribed to species, thereby emphasizing a need to intensify AMF identification in cropping systems.


A personalized mRNA vaccine has exhibited potential in the treatment of pancreatic cancer.
This commentary discusses a ground-breaking study on the use of personalized mRNA cancer vaccines for treating pancreatic ductal adenocarcinoma (PDAC), a highly malignant form of cancer. The study, which capitalizes on lipid nanoparticles for mRNA vaccine delivery, aims to induce an immune response against patient-specific neoantigens and offers a potential ray of hope for improving patient prognosis. Initial results from a Phase 1 clinical trial indicated a significant T cell response in half of the subjects, opening new avenues for PDAC treatment. However, despite the promising nature of these findings, the commentary emphasizes the challenges that remain. These include the complexity of identifying suitable antigens, the possibility of tumor immune escape, and the requirement for extensive large-scale trials to confirm long-term safety and efficacy. This commentary underscores the transformative potential of mRNA technology in oncology while highlighting the hurdles that need to be overcome for its widespread adoption.


In vivo cytokine responses in gut-associated lymphoid tissue (GALT) and spleen following oral administration of staphylococcal enterotoxin B.
The mechanisms responsible for oral tolerance have been analyzed using various antigens. The induction of oral nonresponsiveness to low doses of Staphylococcal Enterotoxin B (SEB), in which SEB-reactive clonal anergy and deletion are involved, has also been confirmed. However, few reports have examined the cytokine milieu of the mucosal and peripheral lymphoid tissue during tolerance induction after the oral administration of SEB. In this study, to elucidate the mechanism responsible for the oral tolerance to low dose of SEB, the cytokine responses of the gut-associated lymphoid tissues (GALT) and the spleen were examined using the reverse transcription-polymerase chain reaction (RT-PCR) method. After the oral administration of a single low dose of SEB, the expressions of Th2 and TGF-beta, and to a lesser extent Th1 mRNA were observed in the mucosa. In contrast, following repeated oral low doses of SEB, in a manner different from previous results using conventional antigens, no cytokine enhancements were demonstrated in the GALT or the spleen. In conclusion, the involvement of unknown inhibitory or regulatory cytokines, together with SEB-reactive clonal anergy and deletion, is suggested in the induction of oral tolerance to low dose SEB.


Mild recessive epidermolytic hyperkeratosis associated with a novel keratin 10 donor splice-site mutation in a family of Norfolk terrier dogs.
Epidermolytic hyperkeratosis in humans is caused by dominant-negative mutations in suprabasal epidermal keratins 1 and 10. However, spontaneous keratin mutations have not been confirmed in a species other than human. To describe an autosomal recessive, mild, nonpalmar/plantar epidermolytic ichthyosis segregating in an extended pedigree of Norfolk terrier dogs due to a splice-site mutation in the gene encoding keratin 10 (KRT10). Dogs were evaluated clinically, and skin samples were examined by light and electron microscopy. Genomic DNA samples and cDNA from skin RNA were sequenced and defined a mutation in KRT10. Consequences of the mutation were evaluated by assessing protein expression with immunohistochemistry and Western blotting and gene expression with real-time RT-PCR (reverse transcriptase-polymerase chain reaction). Adult dogs with the disease had generalized, pigmented hyperkeratosis with epidermal fragility. Light microscopic examination defined epidermolysis with hyperkeratosis; ultrastructural changes included a decrease in tonofilaments and abnormal filament aggregation in upper spinous and granular layer keratinocytes. Affected dogs were homozygous for a single base GT-->TT change in the consensus donor splice site of intron 5 in KRT10. Keratin 10 protein was not detected with immunoblotting in affected dogs. Heterozygous dogs were normal based on clinical and histological appearance and keratin 10 protein expression. The mutation caused activation of at least three cryptic or alternative splice sites. Use of the cryptic sites resulted in transcripts containing premature termination codons. One transcript could result in shortening of the proximal portion of the 2B domain before the stutter region. Quantitative real-time PCR indicated a significant decrease in KRT10 mRNA levels in affected dogs compared with wild-type dogs. This disease is the first confirmed spontaneous keratin mutation in a nonhuman species and is the first reported recessive form of epidermolytic hyperkeratosis.


Synthesis of pyrazolo[1,5-a]pyrimidine linked aminobenzothiazole conjugates as potential anticancer agents.
A series of pyrazolo[1,5-a]pyrimidine linked 2-aminobenzothizole conjugates (6a-t) were synthesized and evaluated for their anticancer activity against five human cancer cell lines. Among them two compounds 6p and 6m showed significant anticancer activity with IC50 values ranging from 2.01 to 7.07 and 1.94-3.46 μM, respectively. Moreover, cell cycle arrest in G2/M and reduction in Cdk1 expression level were observed upon treatment of these compounds and they also induced caspase-3 dependent apoptosis. This was further confirmed by staining as well as DNA fragmentation analysis.


COHgb levels predict the long-term development of acute myocardial infarction in CO poisoning.
There are several studies evaluating the cardiac effects of carbon monoxide (CO) poisoning during the acute period; however, the number of studies evaluating the long-term cardiac effects is limited. The present study aimed to evaluate the effects of blood carboxyhemoglobin (COHb) levels, elevated due to CO poisoning on the long-term development of acute myocardial infarction (AMI). This cross-sectional cohort study included a total of 1013 consecutive patients who presented to the emergency department (ED) due to CO poisoning, between January 2005 and December 2007. The diagnosis of CO poisoning was made according to the medical history and a COHb level of greater than 5%. In terms of AMI development, the patients were followed up for an average of 56 months. At the end of follow-up, 100 (10%) of 1013 patients experienced AMI. Carboxyhemoglobin levels at the time of poisoning were higher among those who were diagnosed with AMI compared to those who were not (55%±6% vs 30%±7%; P<.001). Using a multivariate Cox proportional hazards model with forward stepwise method, age, COHb level, CO exposure time, and smoking remained associated with an increased risk of AMI after adjustment for the variables found to be statistically significant in a univariate analysis. According to a receiver operating characteristic curve analysis, the optimal cutoff value of COHb used to predict the development of AMI was found to be greater than 45%, with 98% sensitivity and 94.1% specificity. In patients presenting to the ED with CO poisoning, COHb levels can be helpful for risk stratification in the long-term development of AMI.


Patterns of in-stent restenosis after placement of NIR gold-coated stents in unselected patients.
The aim of this study was to assess the incidence and angiographic patterns of in-stent restenosis 6 months after the implantation of NIR gold-coated stents in an unselected patient population. One hundred and sixteen consecutive patients were treated with the implantation of 149 NIR gold-coated stents. The majority of the patients (52%) had unstable angina or acute myocardial infarction. The baseline lesion morphology was complex in 78% of cases; the mean lesion length was 18 +/- 5 mm. The procedural success rate was 97%. Subacute stent thrombosis occurred in three patients (2.6%). During the 6-month follow-up, there were 2 deaths and 22 subjects (19.5%) underwent target vessel revascularization. The 6-month event-free survival was 60%. The angiographic restenosis rate was 32%. In 83% of the cases, the morphology of the restenosis was proliferative; in the remaining 17%, it presented as total occlusion. In conclusion, the restenosis rate after NIR gold-coated stent implantation in high-risk patients is similar to that reported using other stent designs. However, restenosis was always diffuse, involving the overall stent length and extending beyond the margins, thus indicating a greater proliferative neointimal response to this device.


Preferential microRNA targeting revealed by in vivo competitive binding and differential Argonaute immunoprecipitation.
MicroRNAs (miRNAs) have been described to simultaneously inhibit hundreds of targets, albeit to a modest extent. It was recently proposed that there could exist more specific, exceptionally strong binding to a subgroup of targets. However, it is unknown, whether this is the case and how such targets can be identified. Using Argonaute2-ribonucleoprotein immunoprecipitation and in vivo competitive binding assays, we demonstrate for miRNAs-21, -199-3p and let-7 exceptional regulation of a subset of targets, which are characterized by preferential miRNA binding. We confirm this finding by analysis of independent quantitative proteome and transcriptome datasets obtained after miRNA silencing. Our data suggest that mammalian miRNA activity is guided by preferential binding of a small set of 3'-untranslated regions, thereby shaping a steep gradient of regulation between potential targets. Our approach can be applied for transcriptome-wide identification of such targets independently of the presence of seed complementary sequences or other predictors.


Partitioning defective 6 homolog alpha (PARD6A) promotes epithelial-mesenchymal transition via integrin β1-ILK-SNAIL1 pathway in ovarian cancer.
Partitioning-defective protein 6 (Par6) family proteins have been demonstrated to be closely associated with the occurrence and development of cancers. It is well accepted that dysregulation of epithelial-mesenchymal transition (EMT) greatly contributes to carcinogenesis and metastases of ovarian cancer. So far, the roles of Par6 in EMT of ovarian cancer are not clear. Functional experiments were carried out to study the roles of PARD6A in EMT of ovarian cancer in vitro and in vivo, and EMT pathways potentially affected by PARD6A expression were screened. We found that PARD6A was significantly highly expressed in tissues of ovarian cancer patients in III-IV stages, poorly differentiated or with lymphatic metastases versus I-II stages, moderately or well differentiated, or without lymphatic metastases, respectively. PARD6A knockdown suppressed EMT of SKOV3 and A2780 cells in vitro and ovarian cancer metastasis in vivo, while overexpression of PARD6A promoted EMT in HO8910 and OVCAR8 cells. It was indicated that PARD6A affected EMT of ovarian cancer cells through SNAIL1 signaling pathway and subsequently modulated the expression of VIMENTIN and E-cadherin, which was further confirmed by knockdown and overexpression of SNAIL1 experiments. PARD6A was also demonstrated to regulate expression of SNAIL1 by modulating integrin β1 and ILK proteins, specifically it was shown that the transcription of SNAIL1 was regulated by ILK in this study. In addition, expression of ILK in ovarian cancer tissues was demonstrated to be correlated with tumor stages and lymphatic metastases clinically. In this study, we identified a novel role of PARD6A as an inducer of cell migration and invasion, which is likely to play an important role in metastasis of ovarian cancer. The molecular pathways of EMT mediated by PARD6A-Integrin β1-ILK-SNAIL1 and finally implemented by E-cadherin and VIMENTIN may provide a novel strategy for drug development for ovarian cancer therapy in the near future.


Lung transplantation.
Although we have not yet obtained the survival results that have been observed in heart and renal transplantation, the survival rate in lung transplantation is improving. Because the lung is the only organ that is continuously exposed to the environment after transplantation, infection continues to be the major cause of early and late morbidity and mortality. Bronchiolitis obliterans, the second most common cause of late morbidity and mortality, is a progressive and currently untreatable condition resulting in lung dysfunction. The cause of this condition after transplantation is likely multifactorial and related to processes that result in allograft lung injury, such as rejection, bacterial infection, and cytomegalovirus infection. Future improvement in intermediate and long-term survival after lung transplantation will largely depend on prevention and long-term control of infection and subclinical rejection.


Expression, purification and characterization of murine Dkk1 protein.
Dickkopf-1 (Dkk1) protein is a secreted inhibitor of canonical Wnt signaling and modulates that pathway during embryonic development. It is also implicated in several diseases and hence Dkk1 is a potential target for therapeutic intervention. In the present study 6His-tagged Dkk1 expression and secretion was assessed in five mammalian cell types. Only FreeStyle 293-F cells showed significant Dkk1 protein expression in culture medium. High and stable expression of the Dkk1 protein was obtained from a selected stable FreeStyle 293-F clone 3F8, that grows in suspension in serum-free medium. The 3F8 clone showed a high Dkk1 production level (10mg/L) for up to 2 months of culture. A one step purification procedure resulting in large amounts of highly pure and active Dkk1 protein was developed. Purified Dkk1 binds its receptors LRP5 and LRP6, and is able to dose dependently inhibit canonical Wnt signaling. Recombinant Dkk1 is glycosylated, but this modification is not essential for its biological activity. In summary, an abundant source of pure and functionally active Dkk1 protein is developed that will support the identification of inhibitors such as neutralizing antibodies that could find therapeutic use.


Evidence that 17alpha-estradiol is biologically active in the uterine tissue: antiuterotonic and antiuterotrophic action.
17alpha-Estradiol has been considered as the hormonally inactive isomer of 17beta-estradiol. Recently, nongenomic (smooth muscle relaxation) and genomic (light estrogenic activity) effects of 17alpha-estradiol have been reported, but no reports have yet determined its possible antiestrogenic activity. Therefore, this study investigated: the nongenomic action of 17alpha-estradiol on uterine contractile activity and its potential agonist-antagonist activity on uterine growth. Uterine rings from rats were isometrically recorded. Different concentrations (0.2-200 microM) of 17alpha-estradiol were tested on spontaneous contraction and equimolarly compared with 17beta-estradiol. To examine the mechanism of 17alpha-estradiol action, its effect was studied in presence of beta2-antagonist (propranolol), antiestrogens (tamoxifen and ICI 182,780) or inhibitors of protein synthesis (cycloheximide) and transcription (actinomycin D). Moreover, contractions induced by high potassium (KCl) solution or calcium in depolarized tissues by KCl-calcium free solution were exposed to 17alpha-estradiol. Collaterally, we performed an uterotrophic assay in adult ovariectomized rats measuring the uterine wet weight. The administration for three days of 0.3 microM/day/Kg 17beta-estradiol was equimolarly compared with the response produced by 17alpha-estradiol. Antiuterotrophic activity was assayed by administration of 0.3 microM/day/Kg 17beta-estradiol and various doses ratios (1:1, 1:3, 1:5, and 1:100) of 17alpha-estradiol. The estradiol isomers elicited an immediate relaxation, concentration-dependent and reversible on spontaneous contraction. 17alpha-Estradiol presented lower potency than 17beta-estradiol although it did not antagonize 17beta-estradiol-induced relaxation. Relaxation to 17alpha-estradiol was not inhibited by propranolol, tamoxifen, ICI 182,780, cycloheximide or actinomycin D. The KCl contractions were also sensitive to 17alpha-estradiol-induced relaxation and calcium contractions in depolarized tissues were markedly prevented by 17alpha-estradiol, implying a reduction of extracellular calcium influx through voltage-operated calcium channels (VOCCs). Uterotrophic assay detected significant increase in uterine weight using 17alpha-estradiol, which was significantly minor as compared with 17beta-estradiol. 17alpha-Estradiol, at all doses ratios, significantly antagonized the hypertrophic response of 17beta-estradiol. 17alpha-Estradiol induces a relaxing effect, which may be independent of the classical estrogen receptor, nongenomic action, apparently mediated by inactivation of VOCCs. 17alpha-Estradiol is also a weak estrogen agonist (uterotrophic response); likewise, 17alpha-estradiol may act as an antiestrogen (antiuterotrophic response). The overall data document a nongenomic relaxing action and a novel antiestrogenic action of 17alpha-estradiol, which are relevant in estrogen-mediated uterine physiology.


Oxygen consumption by cultured human cells is impaired by a nucleoside analogue cocktail that inhibits mitochondrial DNA synthesis.
We evaluated oxygen consumption rates in human cells cultured in the presence of a nucleoside analog reverse transcriptase inhibitor (NRTI) cocktail that inhibits mitochondrial DNA synthesis. We treated a proliferating human lymphocyte cell line and a primary culture of human adipose cells with antiretroviral drugs (AZT+ddC+d4T). The effects of these drugs on mitochondrial DNA (mtDNA) levels and oxygen consumption rates were evaluated using semi-quantitative real-time PCR and an on-line monitoring Clark electrode system. We found that the NRTI treatment lowered oxygen consumption rates and inhibited mitochondrial DNA replication in human cell cultures. Inhibition of oxygen consumption was linearly proportional to inhibition of mtDNA replication. These results show for the first time that mitochondrial respiration is impaired in NRTI sensitive cells. The linear relationship between NRTI inhibition of respiration and NRTI inhibition of mtDNA replication indicates that small decreases in mtDNA levels can lead to respiratory deficits in the tissues of patients treated with anti-HIV drugs. We propose a model that takes into account the small differences in metabolic dynamics between peripheral and axial/visceral fat tissues. This model explains how NRTI-related respiratory deficits may lead to the presentation of opposing lipodystrophic syndromes in same patient.


NGR-modified pH-sensitive liposomes for controlled release and tumor target delivery of docetaxel.
As current tumor chemotherapy faces many challenges, it is important to develop drug delivery systems with increased tumor-targeting ability, enhanced therapeutic effects and reduced side effects. In this study, a pH-sensitive liposome was constructed containing CHEMS-anchored PEG2000 for extended circulation and NGR peptide as the targeting moiety. The NGR-modified docetaxel-loaded pH-sensitive extended-circulation liposomes (DTX/NGR-PLL) prepared possess suitable physiochemical properties, including particle size of approximately 200nm, drug encapsulation efficiency of approximately 70%, and pH-sensitive drug release properties. Experiments performed in vitro and in vivo on human fibrosarcoma cells (HT-1080) and human breast adenocarcinoma cells (MCF-7) verified the specific targeting ability and enhanced antitumor activity to HT-1080 cells. The results of intravenous administration demonstrated that NGR-modified liposomes can significantly and safely accumulate in tumor tissue in xenografted nude mice. In conclusion, the liposomes constructed hold promise as a safe and efficient drug delivery system for specific tumor treatment.


Effect of the immunomodulant 2-cyanaziridine derivative BM 41.332 on adjuvant arthritis in the rat.
2-Cyan-1-[(2-methoxy-6-methyl-pyridin-3-yl)-methyl]-aziridine (BM 41.332), a derivative of the immuno-stimulant group of 2-cyanaziridines, showed a therapeutic action in adjuvant arthritis in the rat. Although it does not possess any direct anti-inflammatory action, BM 41.332 showed activity which differed clearly from conventional antirheumatic agents such as cyclophosphamide, glucocorticoids, levamisole or indometacin.


Preconception hemoglobin A1c concentration in healthy women is not associated with fecundability or pregnancy loss.
To examine the relationship of preconception hemoglobin A1c, a marker of cumulative exposure to glucose over the preceding 2-3 months, with time to pregnancy, pregnancy loss, and live birth among fecund women without diagnosed diabetes or other medical diseases. A secondary analysis of a prospective cohort of women participating in the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial. Four US academic medical centers. A total of 1,194 healthy women aged 18-40 years with a history of one or two pregnancy losses attempting spontaneous conception were observed for up to six cycles while attempting pregnancy and throughout pregnancy if they conceived. Not applicable. Time to pregnancy, human chorionic gonadotropin pregnancy, clinical pregnancy, pregnancy loss, and live birth. Although increasing preconception A1c level was associated with reduced fecundability (fecundability odds ratio [FOR] per unit increase in A1c 0.74; 95% confidence interval [CI] 0.57, 0.96) in unadjusted models and models adjusted for age, race, smoking and treatment arm (FOR 0.79; 95% CI 0.60, 1.04), results were attenuated after further adjustment for body mass index (FOR 0.91; 95% CI 0.68, 1.21). Preconception A1c levels among women without diagnosed diabetes were not associated with live birth or pregnancy loss. Among healthy women without diagnosed diabetes, we observed no association of A1c with live birth or pregnancy loss. The association between A1c and fecundability was influenced by body mass index, a strong risk factor for both diabetes and infertility. These data support current recommendations that preconception A1c screening should be reserved for patients with risk factors for diabetes. ClinicalTrials.gov: NCT00467363.


Configurational fingerprints of multicellular living systems.
Cells cooperate as groups to achieve structure and function at the tissue level, during which specific material characteristics emerge. Analogous to phase transitions in classical physics, transformations in the material characteristics of multicellular assemblies are essential for a variety of vital processes including morphogenesis, wound healing, and cancer. In this work, we develop configurational fingerprints of particulate and multicellular assemblies and extract volumetric and shear order parameters based on this fingerprint to quantify the system disorder. Theoretically, these two parameters form a complete and unique pair of signatures for the structural disorder of a multicellular system. The evolution of these two order parameters offers a robust and experimentally accessible way to map the phase transitions in expanding cell monolayers and during embryogenesis and invasion of epithelial spheroids.


Multi-institutional development and validation of a nomogram to predict recurrence after curative resection of gastric neuroendocrine/mixed adenoneuroendocrine carcinoma.
To establish a novel nomogram to predict individual 1, 3, and 5 years disease-free survival (DFS) of patients with gastric neuroendocrine carcinoma/mixed adenoneuroendocrine carcinoma [(MA)NEC]. Among patients undergoing radical resection of gastric (MA)NEC, there is still a high tendency for relapse. A retrospective analysis of 777 patients with gastric (MA)NEC at 23 centers in China from 2004 to 2015 was performed. Based on the established nomogram, which included age, ASA, pT, pN and Ki67, the overall patients were divided into low-risk group (LRG) and high-risk group (HRG). The median follow-up time was 40 months (1-169 months). The C-index, AUC and time-ROC of the nomogram were significantly higher than that of the 8th edition AJCC and ENETS TNM staging systems. The 3-year DFS of patients in HRG generated by the nomogram was significantly lower than that in LRG (all patients: 35% vs 66.9%, p < 0.001), and there were still significant differences in stratified analysis of the TNM staging systems. The local recurrence rate (10.5% vs 2.6%) and distant recurrence rate (45.1% vs 22.6%) in HRG were significantly higher than those in LRG, especially in anastomotic recurrence (6.3% vs 2%), liver recurrence (20.7% vs 13.4%) and peritoneal metastasis (12.7% vs 2.6%). Compared with AJCC and ENETS TNM staging systems, the established novel validated nomogram had a significantly better prediction ability for DFS and recurrence patterns in patients with gastric (MA)NEC. It can also compensate for the shortcomings of existing AJCC and ENETS TNM staging in predicting individual recurrence risk.


Inefficiencies in Residency Matching Associated with Gale-Shapley Algorithms.
To investigate emerging trends and increasing costs in the National Residency Matching Program (NRMP) and San Francisco Residency and Fellowship Match Services (SF Match) associated with the current applicant/program Gale-Shapley-type matching algorithms. A longitudinal observational study of behavioral trends in national residency matching systems with modeling of match results with alternative parameters. We analyzed publicly available data from the SF Match and NRMP websites from 1985 to 2020 for trends in the total number of applicants and available positions, as well the average number of applications and interviews per applicant for multiple specialties. To understand these trends and the algorithms' effect on the residency programs and applicants, we analyzed anonymized rank list and match data for ophthalmology from the SF Match between 2011 to 2019. Match results using current match parameters, as well as under conditions in which applicant and/or program rank lists were truncated, were analyzed. Both the number of applications and length of programs' rank lists have increased steadily throughout residency programs, particularly those with competitive specialities. Capping student rank lists at 7 programs, or less than 80% of the average 8.9 programs currently ranked, results in a 0.71% decrease in the total number of positions filled. Similarly, capping program rank lists at 7 applicants per spot, or less than 60% of the average 11.5 applicants ranked per spot, results in a 5% decrease in the total number of positions filled. While the number of ophthalmology positions in the US has increased only modestly, the number of applications under consideration has increased substantially over the past two decades. The current study suggests that both programs and applicants rank more choices than are required for a nearly-complete and stable match, creating excess cost and work for both applicants and programs. "Stable-marriage"-type algorithms induce applicants and programs to rank as many counter-parties as possible to maximize individual chances of optimizing the match.


Ethanol-induced jejunal microvascular and morphological injury in relation to histamine release in rabbits.
To investigate the relation between ethanol-induced jejunal microvascular injury, morphological changes, and histamine release, the present study examined whether the attenuation of microvascular effect of ethanol by 16,16-dimethyl prostaglandin E2 (dmPGE2) (reported by us previously) was associated with an attenuation of epithelial damage and histamine release. Rabbits were used. Mucosal microvascular injury was assessed by determining jejunal plasma protein loss (JPPL), histamine release by measuring histamine concentration of the gut effluent, and epithelial damage by routine histology. (1) During 90-minute jejunal ethanol perfusion, there was a direct relation between the time course of histamine release and that of JPPL. (2) dmPGE2 attenuated the ethanol-induced JPPL and histamine release, and the decrease in JPPL was directly proportional to the decrease in histamine release. (3) dmPGE2 did not alleviate ethanol-induced epithelial damage. (4) Ketotifen (a mast cell stabilizer), similar to dmPGE2, attenuated ethanol-induced JPPL and histamine release. (5) Ethanol caused histamine release by the jejunum in vitro; this was attenuated by dmPGE2 and also by phloretin (a mast cell stabilizer). It appears that (1) ethanol causes JPPL by inducing release of mediators from mucosal mast cells. (2) dmPGE2 attenuates JPPL by stabilizing mast cells. (3) The ethanol-induced mucosal microvascular injury is directly related to histamine release but not to epithelial damage.


CT diagnosis of traumatic pericardium rupture.
A case of traumatic rupture of the pericardium secondary to a motor vehicle accident is presented. Diagnosis of this condition was made prior to surgery by CT.


An urokinase receptor antagonist that inhibits cell migration by blocking the formyl peptide receptor.
Urokinase receptor (uPAR) plays a key role in physiological and pathological processes sustained by an altered cell migration. We have developed peptides carrying amino acid substitutions along the Ser(88)-Arg-Ser-Arg-Tyr(92) (SRSRY) uPAR chemotactic sequence. The peptide pyro glutamic acid (pGlu)-Arg-Glu-Arg-Tyr-NH2 (pERERY-NH(2)) shares the same binding site with SRSRY and competes with N-formyl-Met-Leu-Phe (fMLF) for binding to the G-protein-coupled N-formyl-peptide receptor (FPR). pERERY-NH(2) is a dose-dependent inhibitor of both SRSRY- and fMLF-directed cell migration, and prevents agonist-induced FPR internalization and fMLF-dependent ERK1/2 phosphorylation. pERERY-NH(2) is a new and potent uPAR inhibitor which may suggest the generation of new pharmacological treatments for pathological conditions involving increased cell migration.


Dense retrograde amnesia, intact learning capability and abnormal forgetting rate: a consolidation deficit?
Following a thoracic trauma, which caused brain hypoxia, a 24-year-old man presented with a dense retrograde amnesia for events, persons and environments that spanned his whole life before injury. Knowledge acquired at school or through the media were equally lost, with the exception of arithmetical skills and some geographical knowledge. No deficit was apparent in language, object recognition, motor skills and intellectual tests. Anterograde memory was marked by very efficient learning capacity, an almost perfect retention of information at delay interval of 4 hours and pathologically rapid forgetting at longer delays. Informal observations agreed with test performance in showing that he could relearn facts of the past and easily acquire new information, but tended to lose these memories if the information was not frequently rehearsed. PET showed a hypometabolism of the posterior temporal lobes. Though some points remain obscure, we propose that a consolidation deficit hypothesis provides the most sensible interpretation of this peculiar pattern of memory deficit.


Characterization of the submarine disposal of a Bayer effluent (Gardanne alumina plant, southern France): I. Size distribution, chemical composition and settling rate of particles forming at the outfall.
The submarine discharge of the high pH clarified Bayer effluent of the Gardanne alumina plant (Marseille region, France) leads to the formation of concretions at the outfall 324 m underwater and to a plume of white particles. The bulk chemical composition of the concretions has been determined by SF-ICP-MS. Mg and Al are the major elements measured with concentrations of a few hundred mg g-1. Ca and S are also found at concentrations in the range of mg g-1. Among the measured trace elements there is a specific interest in As and V because of environmental concerns pointed out by regulation authorities. Their concentrations are of tens to thousands μg g-1, respectively. Concentrations of the other elements are in the range of a few ng g-1 to few hundreds μg g-1. In order to constrain the dispersion of particles in the environment and to understand how chemical elements can be scavenged from or released to seawater, the size distribution of particles composing the concretions has been measured by settling rate experiments and, for each size class of particles, their chemical composition has been determined. For example, As and V are mainly associated to particles with mean diameters between 15.6 and 63 μm and settling rates around 96 m d-1. Overall, all the main elements (Mg, Al, Ca, S) composing concretions are associated to this size class of particles which represents 53-60% of the total concretion mass.


Molecular typing of Neisseria gonorrhoeae causing repeated infections: evolution of porin during passage within a community.
Thirty-three Neisseria gonorrhoeae isolates from 15 persons infected multiple times with the same serovar were compared using por gene sequencing, opa-typing, and arbitrarily primed-polymerase chain reaction. All three molecular techniques were more discriminatory than serotyping and identified differences between some isolates belonging to the same serovar. Although there were differences among Por sequences within some serovars, 10 of 15 subjects became reinfected with gonococci expressing identical Por proteins. Sequence analysis of por genes revealed evidence of horizontal genetic exchange and point mutations in potential surface-exposed regions during passage in the community.


Preprocedural levels of C-reactive protein and leukocyte counts predict 9-month mortality after coronary angioplasty for the treatment of unprotected left main coronary artery stenosis.
An accurate preprocedural risk stratification scheme for patients with unprotected left main coronary artery (ULMCA) stenosis who are undergoing coronary stenting is lacking. We examined the predictive value of preprocedural levels of C-reactive protein (CRP), fibrinogen, and leukocyte counts with respect to 9-month clinical outcomes after stenting of the ULMCA stenosis. Levels of CRP, fibrinogen, and leukocyte count were prospectively measured in 83 patients undergoing stenting of the ULMCA. A drug-eluting stent was used in 42 patients, and a bare metal stent was used in 41. The end point of the study was death and the combination of death and myocardial infarction (MI). By the 9-month follow-up, there were 11 deaths (13%), 7 MIs (8%), and 16 target lesion revascularizations (19%). Death and death/MI occurred in 19% and 31%, respectively, of 59 patients with high serum levels of CRP (>3 mg/L) but in none of 24 patients with normal CRP levels (for death, P=0.02; for death/MI, P=0.006). In multivariate analysis, the highest tertiles of CRP level (P=0.028) and leukocyte count (P=0.002) were the only independent predictors of death. The highest tertiles of CRP level (P=0.002) and leukocyte count (P=0.002) and acute coronary syndromes (P=0.05) were the only independent predictors of the combined end point death/MI. Elevated preprocedural levels of CRP indicate an increased risk of death and death/MI after ULMCA stenting. Inflammatory risk assessment in patients with ULMCA stenosis may be useful for selecting patients for percutaneous coronary interventions with very low risk.


Alternaria alternata infection causing rhinosinusitis and orbital involvement in an immunocompetent patient.
Invasive fungal rhinosinusitis is a rare infection that occurs primarily in immunocompromised patients. The fungal pathogen Alternaria alternata is rarely associated with rhinosinusitis. We report a case of A. alternata rhinosinusitis in an immunocompetent patient.


Development and Psychometric Properties of the Adversity and Stress Scale (ASS): Validation in the Adult Mexican Population.
Since stress is known to play a role in the development of physical and mental illness, empirically validated measurements are required to assess the effect of adverse events such as the COVID-19 pandemic. The purpose of this study was to develop and evaluate the psychometric properties of the Adversity and Stress Scale (ASS). A sample of 3937 adults living in Mexico was used. The structure of the instrument was evaluated using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). Construct validity was measured through associations between the ASS and psychological symptoms. In the EFA, the relational and contextual dimensions of stress were identified. A good fit was obtained in the CFA (CFI = 0.980, RMSEA = 0.040). The ASS score was associated with all the selected variables in the expected direction, and internal consistency was α = .86. The ASS is a valid, reliable measure, with the potential to be used in other adverse events.


Transient steatorrhea following episodes of mild diarrhea in early infancy.
Fecal fat excretion was studied after a mild episode of diarrhea in eight infants for whom adequate control data were available. Mean age of onset of diarrhea was 28 days. Duration of the episode, defined as the number of days until the infant was again feeding and libitum, averaged 5.1 days. Balance studies were carried out 3 to 13 days later. Mean fecal fat excretion rose from a prediarrhea value of 2.9 +/- 1.4 gm/day to 8.7 +/- 3.1 gm/day following diarrhea (P less than 0.001). Restudy of five infants one month later showed persistent steatorrhea in one. Mild transient steatorrhea may follow mild diarrhea in infancy and should be considered in infants who are slow to gain weight subsequent to an episode of diarrhea.


Left ventricular assist device: a functional comparison with heart transplantation.
A growing number of patients with end-stage heart failure undergo implantation of ventricular assist devices as a bridge to heart transplantation. In this study we investigated whether functional and haemodynamic recovery after implantation is sufficient to warrant the use of them as long-term alternative to heart transplantation. We compared peak VO(2) of a group of patients three months after implantation of a ventricular assist device and three months after heart transplantation. Furthermore, we analysed the degree of haemodynamic recovery, by comparing plasma levels of BNP and creatinine before and after implantation of the device. After implantation of a ventricular assist device, exercise capacity improved considerably; three months after implantation peak VO(2) was 20.0+/-4.9 ml/kg/min (52% of predicted for age and gender). After heart transplantation exercise capacity improved even further; 24.0+/-3.9 ml/ kg/min (62% of predicted for age and gender) (p<0.001). In the three months after implantation, BNP plasma levels decreased from 570+/-307 pmol/l to 31+/-25 pmol/l and creatinine levels decreased from 191+/-82 mumol/l to 82+/-25 mumol/l, indicating significant unloading of the ventricles and haemodynamic recovery. With regard to functional and haemodynamic recovery, the effect of implantation of a ventricular assist device is sufficient to justify its use as an alternative to heart transplantation. (Neth Heart J 2008;16:41-6.).


Comparative ecotoxicology study of two neoteric solvents: Imidazolium ionic liquid vs. glycerol derivative.
In this study we have compared the acute ecotoxicity of two solvents, with very different structure and origin, but sharing many physical-chemical properties, so they can be used for similar purposes; a well-known ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF6]) and a solvent partially derived from biomass, 3-bis(2,2,2-trifluoroethoxy)propan-2-ol (BTFIP). We have used three biomodels (Vibrio fischeri, Daphnia magna and Danio rerio) and performed the comparison applying the Environmental, Health and Safety (EHS) hazard assessment. According to the results, ecotoxicity of [BMIM][PF6] and BTFIP is quite similar in the simplest model Vibrio fischeri, while in Daphnia magna [BMIM][PF6] is clearly more toxic. However, in Danio rerio, toxicity of these chemicals is again quite similar and both can be classified as "nontoxic". The higher index value of [BMIM][PF6] in water mediate effect in the EHS assessment indicates that this ionic liquid is more dangerous than BTFIP, although accumulation and degradation properties have not been taken into account. Further studies will be necessary to ascertain these conclusions.


The vascular protective properties of kinsenoside isolated from Anoectochilus roxburghii under high glucose condition.
Anoectochilus roxburghii is a traditional Chinese herb used for the treatment of diabetes and some other diseases. The vascular protective effect of its major active ingredient, kinsenoside, in high glucose conditions was investigated in in vivo and in vitro experiments. In in vivo tests, kinsenoside (50 and 100mg/kg) efficiently lowered blood glucose and cholesterol levels and it enhanced the oxidation resistance of diabetic mice induced by streptozotocin. In the in vitro assay, kinsenoside (20 and 50 μg/mL) markedly inhibited changes in various biochemical substances (nitric oxide (NO), lactic dehydrogenase (LDH), superoxide dismutase (SOD), and catalase (CAT)) in human umbilical vein endothelial cells (HUVECs) damaged by high glucose (35 mM) and restored vascular endothelial structure by balancing the matrix metalloproteinases-the tissue inhibitors of matrix metalloproteinases (MMP-TIMP) system. The vascular protective effects of kinsenoside were speculated to be attributed to oxidative stress inhibition and the reduction of nuclear factor kappa B (NF-κB) mRNA expression levels in high glucose conditions. Moreover, histological examination, including hematoxylin-eosin (H&E) staining, masson trichrome (Masson) staining, and periodic Schiff-methenamine (PASM) staining, greatly supported the morphological and functional amelioration of diabetes-related changes in mice aortas after kinsenoside (20 and 50 μg/mL) treatment. These results indicated that kinsenoside might be a promising agent for the treatment of diabetic vascular disease.


Treatment of urethral defects: skin, buccal or bladder mucosa, tube or patch? An experimental study in dogs.
We studied 3 graft materials and 2 urethroplasty techniques in 24 adult male mongrel dogs. The animals were divided into 2 equal groups. In group 1 a 4 cm. segment of perineal urethra was excised and tubed urethroplasty was performed using free full-thickness skin, buccal and bladder mucosa grafts in 4 dogs each. In group 2 a 4 cm. urethral strip was excised and onlay urethroplasty was performed using the same graft materials in 4 dogs each. Retrograde urethrography was done and the animals were sacrificed at week 12. Autopsy specimens were calibrated with a 10Fr catheter. Hematoxylin and eosin stained sections were examined. Masson's trichrome stain was used to determine the extent of fibrosis. Urethral stricture was diagnosed by radiology and confirmed by calibration in 8 of the 12 dogs (66%) in group 1 but in only 1 of the 12 (8%) in group 2 (p <0.004). Buccal mucosa grafts were associated with the lowest stricture rate of 12%, followed by 37% for bladder mucosa and 62% for skin (p <0.2). There was no difference in neovascularization among the 3 grafts. Graft shrinkage was less than 10% for buccal mucosa compared with 20% to 40% for skin and bladder mucosa. The shrinkage rate was similar for the onlay and tube techniques. The intensity of chronic inflammation and fibrosis was highest in the skin grafts. Circumferential fibrosis was noted in association with tubed urethroplasty but not with the onlay technique. The theoretical advantages of buccal mucosal grafts were pathologically demonstrated. When possible, grafts should be used as an onlay rather than as a complete tube.


Treatment failure in trichomoniasis and persistence of the parasite after Lactobacillus immunotherapy; two case reports.
This report describes the clinical and laboratory observations on two patients with a Trichomonas vaginalis infection resistant to metronidazole. The metronidazole resistance was confirmed in in vitro cultures under aerobic conditions, after in vitro cultivation of the strains. Trichomonas infection persisted during high-dose intravenous metronidazole administration and Lactobacillus immunotherapy was unsuccessful in both patients.


LY2603618, a selective CHK1 inhibitor, enhances the anti-tumor effect of gemcitabine in xenograft tumor models.
Pharmacological inhibition of CHK1 in the absence of p53 functionality leads to abrogation of the S and G2/M DNA damage checkpoints. We report the preclinical therapeutic activity of LY2603618 (CHK1 inhibitor) at inhibiting CHK1 activation by gemcitabine and enhancing in vivo efficacy. The in vivo biochemical effects of CHK1 inhibition in the absence or presence of DNA damage were measured in human tumor xenograft models. Colon, lung and pancreatic xenografts models were treated with gemcitabine, LY2603618, or gemcitabine plus LY2603618. Gemcitabine treatment alone induced a significant increase in CHK1 autophosphorylation over untreated tumors. Co-administration of LY2603618 with gemcitabine showed a clear inhibition of CHK1 autophosphorylation for at least 24 h. Combining LY2603618 with gemcitabine resulted in an increase in H2AX serine 139 phosphorylation, indicating a corresponding increase in damaged DNA in the tumors. LY2603618 abrogated the S-phase DNA damage checkpoint in Calu-6 xenograft tumors treated with gemcitabine but did not significantly alter the G2/M checkpoint. Combining gemcitabine with LY2603618 resulted in a significant increase in tumor growth inhibition in Calu-6, HT-29 and PAXF 1869 xenografts over gemcitabine treatment alone. The best combination efficacy occurred when LY2603618 was given 24 h following dosing with gemcitabine. LY2603618 worked effectively to remove the S-phase DNA damage checkpoint and increase the DNA damage and the antitumor activity of gemcitabine treatment.


The effect of frictional heating and forced cooling on the serum lubricant and wear of UHMW polyethylene cups against cobalt-chromium and zirconia balls.
Hip simulator tests of femoral balls of cobalt-chromium alloy or zirconia against acetabular cups of UHMW polyethylene were run with and without a coolant circulated inside the femoral balls. Without cooling, the wear of polyethylene against zirconia was about 48% lower than with cobalt-chromium alloy, but the steady-state temperature of the zirconia ball was higher (55 degrees C vs. 41 degrees C), and there was more precipitation of protein from the serum, which sometimes formed an adherent layer on the surface of the zirconia. Circulating coolant at 1-20 degrees C markedly reduced the bearing temperatures and the protein precipitation. With coolant at 4 degrees C, wear of the polyethylene against cobalt-chromium alloy was about 26% lower than against zirconia, but the macroscopic and microscopic appearance of the worn polyethylene surfaces were unlike that typically generated in vivo. With or without coolant, the morphology of the polyethylene wear debris was comparable to that generated in vivo, but the ratio of fibrillar to granular debris was higher at the reduced temperature. These results suggested that circulating coolant at an appropriate temperature could avoid overheating (due to non-stop running of the simulator), preventing excessive protein precipitation while providing wear surfaces and wear debris with morphologies closely comparable to those generated in vivo.


Gamabufotalin induces a negative feedback loop connecting ATP1A3 expression and the AQP4 pathway to promote temozolomide sensitivity in glioblastoma cells by targeting the amino acid Thr794.
Temozolomide (TMZ) is one of the most commonly used clinical drugs for glioblastoma (GBM) treatment, but its drug sensitivity needs to be improved. Gamabufotalin (CS-6), the primary component of the traditional Chinese medicine "ChanSu," was shown to have strong anti-cancer activity. However, more efforts should be directed towards reducing its toxicity or effective treatment doses. Target fishing experiment, Western blotting, PCR, confocal immunofluorescence and molecular cloning techniques were performed to search for possible downstream signalling pathways. In addition, GBM xenografts were used to further determine the potential molecular mechanisms of the synergistic effects of CS-6 and TMZ in vivo. Mechanistic research revealed a negative feedback loop between ATP1A3 and AQP4 through which CS-6 inhibited GBM growth and mediated the synergistic treatment effect of CS-6 and TMZ. In addition, by mutating potential amino acid residues of ATP1A3, which were predicted by modelling and docking to interact with CS-6, we demonstrated that abrogating hydrogen bonding of the amino acid Thr794 interferes with the activation of ATP1A3 by CS-6 and that the Thr794Ala mutation directly affects the synergistic treatment efficacy of CS-6 and TMZ. As the main potential target of CS-6, ATP1A3 activation critically depends on the hydrogen bonding of Thr794 with CS-6. The combination of CS-6 and TMZ could significantly reduce the therapeutic doses and promote the anti-cancer efficacy of CS-6/TMZ monotherapy.


Using confidence intervals to assess the reliability of instantaneous heart rate and respiratory rate.
Physiological waveform signals collected from unstructured environments are noisy, requiring automated algorithms to assess the reliability of the derived vital signs, such as heart rate (HR) and respiratory rate (RR), before they can be used for automated decision support. We recently proposed a weighted regularized least squares method to estimate instantaneous HR (HR(R)), which readily provides analytically based confidence intervals (CIs). Accordingly, this method can be extended to the estimation of instantaneous RR (RR(R)). In this study, we aim to investigate whether we can use CIs to select reliable HR(R) and RR(R). We calculated HR(R) and RR(R) for 532 and 370 trauma patients, respectively, grouped the rates according to their CIs, and investigated their reliability by determining their ability to diagnose major hemorrhage. The areas under a receiver operating characteristic curve of HR(R) and RR(R) with CI ≤ 5 bpm (beats per minute for HR and breaths per minute for RR) were 0.70 and 0.66, respectively. RR(R) was superior to the average output of the clinical monitor (p < 0.05 by DeLong's test), while HR(R) was equivalent. HR(R) and RR(R) provide a new approach to systematically and automatically assess the reliability of noisy, field-collected vital signs.


Transverse (lateral) instantaneous force of an acoustical first-order Bessel vortex beam centered on a rigid sphere.
In a recent report [F.G. Mitri, Z.E.A. Fellah, Ultrasonics 51 (2011) 719-724], it has been found that the instantaneous axial force (i.e. acting along the axis of wave propagation) of a Bessel acoustic beam centered on a sphere is only determined for the fundamental order (i.e. m=0) but vanishes when the beam is of vortex type (i.e. m>0, where m is the order (or helicity) of the beam). It has also been recognized that for circularly symmetric beams (such as Bessel beams of integer order), the transverse (lateral) instantaneous force should vanish as required by symmetry. Nevertheless, in this commentary, the present analysis unexpectedly reveals the existence of a transverse instantaneous force on a rigid sphere centered on the axis of a Bessel vortex beam of unit magnitude order (i.e. |m|=1) not reported in [F.G. Mitri, Z.E.A. Fellah, Ultrasonics 51 (2011) 719-724]. The presence of the transverse instantaneous force components of a first-order Bessel vortex beam results from mathematical anti-symmetry in the surface integrals, but vanishes for the fundamental (m=0) and higher-order Bessel (vortex) beams (i.e. |m|>1). Here, closed-form solutions for the instantaneous force components are obtained and examples for the transverse components for progressive waves are computed for a fixed and a movable rigid sphere. The results show that only the dipole (n=1) mode in the scattering contributes to the instantaneous force components, as well as how the transverse instantaneous force per unit cross-sectional surface varies versus the dimensionless frequency ka (k is the wave number in the fluid medium and a is the sphere's radius), and the half-cone angle β of the beam. Moreover, the velocity of the movable sphere is evaluated based on the concept of mechanical impedance. The proposed analysis may be of interest in the analysis of transverse instantaneous forces on spherical particles for particle manipulation and rotation in drug delivery and other biomedical or industrial applications.


Current perspectives on the etiology of agnathia-otocephaly.
Agnathia-otocephaly, a rare, sporadic and lethal malformation, is characterized by microstomia (small mouth), aglossia (absence of the tongue), agnathia (absence of the lower jaw) and abnormally positioned ears. It is a principal anomaly derived from the first pharyngeal arch as a consequence of failed mesenchymal migration of the maxillary prominence and atrophy in the development of the mandibular prominences. Unfortunately, these patients have poor prognoses and may succumb to death shortly after birth due to respiratory problems if appropriate airway management is not implemented. Difficulties persist in the prenatal diagnosis of agnathia-otocephalic patients. However, two- and three-dimensional ultrasonography, computed tomography and magnetic resonance imaging technologies now offer significant improvements in refining the resolution of distinctive facial anomalies. This complex disorder can be attributed to both genetic and teratogenic causes, in addition to other unidentifiable factors. Furthermore, studies in model organisms, in particular mice, have unraveled potential genetic pathways that may contribute to the etiology. This article highlights current perspectives on agnathia-otocephaly with a focus on the etiological causes and issues concerning prenatal diagnosis, differential diagnosis, prognosis and genetic counseling. Finally, studies using animal models especially genetically engineered mice are described to comprehend the molecular genetic interactions that may occur during the genesis of this intriguing craniofacial birth defect.


Isospora leptopogoni n. sp. (Apicomplexa: Eimeriidae) from the sepia-capped flycatcher Leptopogon amaurocephalus Tschudi, 1846 (Passeriformes: Rhynchocyclidae) in South America.
Coccidian protozoan species recorded from flycatchers are few, but they have been described with a certain frequency in recent years. In this context, the present study describes a new Isospora sp. from sepia-capped flycatchers Leptopogon amaurocephalus Tschudi, 1846 captured in the Itatiaia National Park and in a reforestation area which is about 60 km away from the park boundaries, in addition to providing a molecular identification via sequencing of the mitochondrial cytochrome c oxidase subunit 1 gene. Isospora leptopogoni n. sp. has oöcysts that are subspheroidal to ovoidal, measuring on average 22.0 × 19.7 μm, with a smooth, bi-layered wall, c.1.7 μm thick. The micropyle is delicate or inconspicuous. Oöcyst residuum is absent, but one to three polar granules are present. Sporocysts are lemon-shaped, measuring on average 14.7 × 9.3 μm, with a knob-like Stieda body and a rectangular to rounded sub-Stieda body. Sporocyst residuum is present, consisting of compactly bounded granules. Sporozoites are vermiform, with refractile bodies and nucleus. Isospora leptopogoni is different from other Isospora spp. mainly due to its lemon-shaped sporocysts, the presence of micropyle and details of Stieda and sub-Stieda bodies. Phylogenetic analysis placed I. leptopogoni close to other Isospora spp. recorded from phylogenetically related hosts and from the same biogeographic region. Finally, the recurrent finding of this coccidian species in the same L. amaurocephalus specimen in a specific locality in the Itatiaia National Park suggests that the dispersion of I. leptopogoni needs continuous transmissions between susceptible passerines as the area of movement of each L. amaurocephalus specimen appears to be quite small.


Angiographic findings of everolimus-eluting as compared to sirolimus-eluting stents: angiographic sub-study from the Randomized Evaluation of Sirolimus-eluting versus Everolimus-eluting stent Trial (RESET).
Several recent randomized trials comparing everolimus-eluting stent (EES) and sirolimus-eluting stent (SES) reported similar clinical outcomes. This study was aimed to clarify the differences in the angiographic findings of EES as compared to SES. Randomized Evaluation of Sirolimus-eluting versus Everolimus-eluting stent Trial is a prospective multicenter randomized open-label trial comparing EES with SES in Japan. From February to July 2010, 3197 patients were randomly assigned to receive either EES or SES. Of these, angiographic sub-study enrolled 571 patients (EES 285 patients, SES 286 patients). Angiograms were assessed qualitatively and quantitatively at procedure and at 8-12 months in the independent core angiographic laboratory. Late loss of the proximal edges tended to be greater in the EES group than that in the SES group (0.12 ± 0.49 vs. 0.04 ± 0.43 mm, P = 0.05), although late loss in the other segments was similar between the 2 groups. Edge restenosis was mainly observed in EES group, whereas body restenosis was demonstrated in half of SES group. Stent fracture was observed only in the SES group (1.5 %), and peri-stent contrast staining (PSS) tended to be more frequently observed in the SES group than in the EES group (3.6 and 1.5 %, P = 0.18). Restenotic response in the proximal edge was more prominent in the EES group as compared to the SES group. Abnormal angiographic findings such as stent fracture and PSS tended to be more frequent in the SES group.


Evaluation of oral health attitude and behavior among a group of dental students in Puducherry, India: A preliminary cross-sectional study.
Oral behavior reflects individual perception on oral health. Behavior and attitude of oral health providers, especially dentists, towards oral health affect their capacity to deliver oral health care services. This attitude plays a important role in determining the oral health condition of population. The purpose of this study is to evaluate the oral health attitude and behavior among a group of dental students in India and to find any gender-based differences in terms of oral health attitude and behavior. A total of 282 dental students of Indira Gandhi Institute of Dental Sciences, SBV University, Puducherry, India participated in the study. A simplified English version of Hiroshima University Dental-Behavioral Inventory (HU-DBI) was adopted. SSP version 2.80 software was used to analyze the data. Chi-square test was used to find the differences in the distribution of "yes" among students from the different academic year as well as between male and female students. Statistical significance was set at P ≤ 0.05. Statistical significance was observed for the responses between the students from different academic years brushing frequency, careful brushing of teeth, using brush with hard bristles, careful self-evaluation of brushing and satisfied appearance of teeth and gums. Male students preferred to use a tooth brush with hard bristles and regular mouth washes than female students. With regards to worrying about bad breath, male students had more "yes" responses than females. Oral health attitude and behavior increased with the increasing levels of dental education, and no significant differences were observed among male and female dental students.


γ-Secretase inhibition promotes fibrotic effects of albumin in proximal tubular epithelial cells.
Albuminuria is an important biomarker of renal dysfunction and is a major mediator of renal damage and fibrosis during kidney disease. The mechanisms underlying albumin-induced renal fibrosis remain unclear. There has been significant interest in γ-secretase activity in tubular epithelial cells in recent times; however, its potential role in albumin-induced fibrosis has not been investigated. The primary aim of this study was to examine the role of γ-secretase in albumin-induced fibrotic effects in proximal tubular cells. The effects of increasing albumin concentrations on fibrosis indicators and mediators in the human HK-2 cell line were examined in the presence and absence of a γ-secretase inhibitor, compound E. Treatment with albumin resulted in a number of pro-fibrotic effects, including up-regulation of fibronectin, TGF-β1 and the EGF-R. Interestingly, similar effects were observed in response to treatment with the γ-secretase inhibitor, compound E. Co-treatment of cells with albumin and an EGF-R inhibitor, AG-1478, resulted in significant inhibition of the observed pro-fibrotic effects, suggesting a major role for the EGF-R in albumin-induced fibrotic events. Albumin-induced effects on the EGF-R appeared to be mediated through inhibition of γ-secretase activity and were dependent on ERK-MAPK signalling. These results provide novel insights into the mechanisms of albumin-induced fibrotic effects in tubular epithelial cells, suggesting important roles for the γ-secretase and the EGF-R. These results suggest that the proposed use of γ-secretase inhibitors as anti-fibrotic agents requires further investigation.


Kinetics of hemopoietic stem cells in a hypoxic culture.
The influence of low oxygen tension on the clonal growth of hemopoietic stem cells in vitro was examined. The numbers of colonies of neutrophil, macrophage, and eosinophil progenitors (CFU-C), derived from human bone marrow, increased at a rate 1.7 times higher in low oxygen tension (7% O2) than in a gas phase that contained air (19% O2). The erythroid (BFU-E) and multipotential (CFU-mix) progenitors increased about 2.4 times in 7% O2, and the increase in the composed cell type of mixed colonies showed no rate difference in either gas phase. Under atmospheric conditions, a mouse mast cell progenitor (CFU-mast) formed colonies, with the addition of 2-mercaptoethanol (2-ME). Under low oxygen tension, the CFU-mast formed colonies without 2-ME, but a further enhancement was observed with the addition of 2-ME. Blood gas analysis of human bone marrow showed a pO2 of 51.8 +/- 14.5 mmHg, which was closed to O2 tension in a gas phase culture media containing 7% O2. This data shows that the physiological O2 tension enhances hemopoietic stem cell proliferation in vitro, and that a part of the enhancing effect by 2-ME is due to a prevention of O2 toxicity at 19% O2.


Sulfhydryl oxidase-catalyzed formation of disulfide bonds in reduced ribonuclease.
Sulfhydryl oxidase isolated from bovine skim milk membrane vesicles catalyzes de novo formation of disulfide bonds with the substrates cysteine, cysteine-containing peptides, and reduced proteins using molecular oxygen as the electron acceptor. Initial rates for sulfhydryl oxidase-catalyzed oxidation of reduced ribonuclease exhibited typical Michaelis-Menten kinetics at low substrate concentrations. Substrate inhibition of the oxidative activity was observed at ribonuclease concentrations greater than 40 microM, similar to that observed with reduced glutathione or other small thiol substrates. The inhibition was more pronounced when ribonuclease activity was used to monitor the rates, presumably due to concentration-dependent formation of nonnative disulfide bonds. Thus, a maximum in the rate of regain of ribonuclease activity was observed at a 40 microM concentration, while optimum recovery was observed at 30 microM. The Michaelis constant obtained with reduced ribonuclease is 17.4 microM which corresponds to a sulfhydryl concentration of 0.14 mM, a value that compares favorably with the best small thiol substrate, reduced glutathione. Disulfide-containing intermediates in the oxidation pathway, as determined by ion-exchange chromatography of alkylated reaction mixtures, appeared to be similar for air oxidation and enzyme-catalyzed oxidation of the protein. The pH optimum, tissue location, and kinetic characteristics of sulfhydryl oxidase are compatible with a suggested physiological function of direct catalysis of disulfide bond formation in secretory proteins or indirect participation through provision of oxidized glutathione for protein disulfide-isomerase-catalyzed thiol/disulfide interchange.


Influence of low doses of an oxazaphosphorine on natural killer activity of human lymphocytes.
The influence of cis-4-sulfoethylthio-cyclophosphamide (mafosfamide) on natural killer cell activity was examined in vitro in order further to elucidate the possible immunological mechanisms of tumor regressions following low-dose oxazaphosphorine therapy. It was observed that cytotoxicity of human blood lymphoid cells was unchanged or reduced when the lymphocytes were pretreated for 24 h with mafosfamide or when the drug was present during incubation with K562 cells. However, when lymphoid cells were preincubated with human leukocyte interferon plus mafosfamide, natural killer activity was enhanced above the level caused by interferon alone. This enhancement was noted at mafosfamide concentrations of 1 nM-1 microM and was only present when the lymphocyte preparation was contaminated with monocytes.


ERK MAPK activation mediates the antiapoptotic signaling of melatonin in UVB-stressed U937 cells.
The pineal gland hormone melatonin has been recently described to downregulate the intrinsic (or damage-induced) pathway of apoptosis in human leukocytes. These properties appear to depend on a specific mitochondrial signaling of melatonin which is associated with a lower generation of reactive oxygen species and a better control of redox-sensitive components such as the antiapoptotic protein Bcl-2. Other elements upstream in this signaling are expected to contribute regulatory roles that remain unexplored. The aim of this study was to investigate whether the extracellular signal-regulated kinase (ERK), which controls the balance between survival and death-promoting genes throughout the MAPK pathway, is involved in the antiapoptotic signaling of melatonin. Human monocytic U937 cells irradiated with UVB light were used as a model of stress-induced apoptosis. In this model we found that pharmacological concentrations of melatonin (1 mM) were able to decrease superoxide anion production, mitochondrial damage, and caspase-dependent apoptosis by improved Bcl-2 levels and decreased Cyt c release in the cytoplasm. Moreover, melatonin increased the phosphorylative activation of ERK 1/2 independently from the presence of UVB stress, and decreased the UVB-mediated activation of the stress kinases p38 MAPK and JNK. The ERK 1/2 inhibitor PD98059, but not the p38 MAPK inhibitor SB203580, abolished to different extents the effects that melatonin had on the UVB-induced ROS generation, mitochondrial dysfunction, and apoptosis. Using these inhibitors, a cross-talk effect between stress and survival-promoting kinases was tentatively identified, and confirmed the hierarchical role of ERK MAPK phosphorylation in the signaling of melatonin. In conclusion, melatonin sustains the activation of the survival-promoting pathway ERK MAPK which is required to antagonize UVB-induced apoptosis of U937 cells. This kinase mediates also the antioxidant and mitochondrial protection effects of this hormonal substance that may find therapeutic applications in inflammatory and immune diseases associated with leukocyte oxidative stress and accelerated apoptosis.


Exocrine pancreatic insufficiency syndrome in CBA/J mice. III. Pathological and genetic analysis.
A clinical and histopathological description of exocrine pancreatic insufficiency syndrome in CBA/J mice is presented. Amelioration of clinical symptoms by pancreatic enzyme replacement therapy is described, as are breeding experiments designed to test the hypothesis that the etiology of this syndrome is a recessive mutation. Our failure to propagate the expected numbers of animals with the syndrome by genetic means leads us to the conclusion that it is not transmitted as an autosomal recessive mutation. Our finding of focal histological lesions of the exocrine pancreas in large numbers of clinically normal CBA/J mice suggests that the CBA/J genetic background is some way predisposes this strain to the spontaneous necrosis and atrophy of exocrine cells that is pathognomonic of this disease.


Human myoblast differentiation: Ca(2+) channels are activated by K(+) channels.
In a paradigm of cellular differentiation, human myoblast fusion, we investigated how a Ca(2+) influx, indispensable for fusion, is triggered. We show how newly expressed Kir2.1 K(+) channels, via their hyperpolarizing effect on the membrane potential, generate a window Ca(2+) current (mediated by alpha 1H T-type Ca(2+) channels), which causes intracellular Ca(2+) to rise.


Assessment of clinical competencies using clinical images and videos "CIVA".
This paper describes an assessment approach of clinical competencies which widens the number of problems and tasks evaluated using videos and images. Clinical Image and Video Assessment (CIVA) was used to assess clinical reasoning and decision making of final year medical students. Forty to fifty clinical videos and images supported by rich text vignette and reviewed by subject matter experts were selected based on examination blueprints for analysis. CIVA scores were correlated with OSCE, Direct Observation Clinical Encounter Exam (DOCEE) and written exam scores, using the 2-sided Pearson correlation analysis, and their reliability was analyzed using Cronbach's Alpha Coefficient. Furthermore, students personally evaluated the CIVA using a 5- point Likert scale. CIVA and OSCE scores showed a high correlation (r = 0.83) in contrast with the correlation scores of the written examination (r = .36) and the DOCEE (r = 0.35). Cronbach's Alpha for the OSCE and CIVA for the first batch was 0.71 and 0.78. As for the second batch it was 0.91 and 0.91 respectively. Eighty-two percent of students were very satisfied or satisfied with the CIVA process, contents and quality. A well constructed CIVA type assessment with a rich authentic vignette and good quality videos and images could be used to assess clinical reasoning and decision making of final year medical students. CIVA is an assessment tool which correlates well with OSCE, compliments the written and DOCEE and is easier to conduct at a possibly reduced cost.


The need to standardize functional outcome in randomized trials of hip fracture: a review using the ICF framework.
The choice of ideal outcome assessment is complex with the ever-growing number of possible instruments found in the orthopaedic literature. It is critical to reach a worldwide consensus approach in identifying the specific measures to be used in study designs for evaluating treatment of patients with hip fracture. In this article, we present results from a systematic review of the measures being used currently to assess functional outcome in randomized trials. We used the International Classification of Functioning Disability and Health (ICF) framework for conceptualizing outcome after hip fracture trauma from a body, individual, and societal perspective. Relevant articles from 1980 to 2008 (week 52) were found using PubMed, Ovid MEDLINE, Cochrane, Ovid Healthstar, EMBASE, and CINAHL. Studies were included if (1) patients were older than 65 years and managed postoperatively after a hip fracture and (2) the studies were randomized and in the English language. The intervention, sample size, follow-up, intention-to-treat analysis, mode of administration, and functional outcome domains and concepts using the ICF were recorded for each study. Ninety-seven studies containing 82 different instruments for assessing functional outcome were included. Those trials with a low risk of bias relied upon standardized patient-reported outcomes when compared with those trials with a high risk of bias that adopted more investigator-developed instruments. Nineteen percent of the trials used the Harris hip score, 14% used the Katz activities of daily living index, and 10% used the new mobility score. We believe that standardized patient-reported outcomes should be used to assess functional outcome after hip fracture and more rigor is needed when conducting surgical trials in this area. Variation in outcome measures across trials leads to several problems. Clinicians may not be able to interpret their findings when different measures are used. Researchers will not be able to calculate summary treatment effects. Our findings are based on a process for delineating the categories from within the ICF framework that may serve, in the future, as a comprehensive foundation of content for outcomes in the area of hip fractures.


Feature-correlation-aware history-preserving-sparse-coding framework for automatic vertebra recognition.
Automatic vertebra recognition from magnetic resonance imaging (MRI) is of significance in disease diagnosis and surgical treatment of spinal patients. Although modern methods have achieved remarkable progress, vertebra recognition still faces two challenges in practice: (1) Vertebral appearance challenge: The vertebral repetitive nature causes similar appearance among different vertebrae, while pathological variation causes different appearance among the same vertebrae; (2) Field of view (FOV) challenge: The FOVs of the input MRI images are unpredictable, which exacerbates the appearance challenge because there may be no specific-appearing vertebrae to assist recognition. In this paper, we propose a Feature-cOrrelation-aware history-pReserving-sparse-Coding framEwork (FORCE) to extract highly discriminative features and alleviate these challenges. FORCE is a recognition framework with two elaborated modules: (1) A feature similarity regularization (FSR) module to constrain the features of the vertebrae with the same label (but potentially with different appearances) to be closer in the latent feature space in an Eigenmap-based regularization manner. (2) A cumulative sparse representation (CSR) module to achieve feed-forward sparse coding while preventing historical features from being erased, which leverages both the intrinsic advantages of sparse codes and the historical features for obtaining more discriminative sparse codes encoding each vertebra. These two modules are embedded into the vertebra recognition framework in a plug-and-play manner to improve feature discrimination. FORCE is trained and evaluated on a challenging dataset containing 600 MRI images. The evaluation results show that FORCE achieves high performance in vertebra recognition and outperforms other state-of-the-art methods.


Ultrasound diagnosis of fetal macrosomia: a comparison of weight prediction models using computer simulation.
To assess the frequency of the diagnosis of macrosomia in relation to differing weight estimation formulae in unselected pregnancies. Computer modeling techniques were employed. Computer modeling software generated correlated fetal biometry measurements according to published British standards, from 37 to 41 weeks' gestation. For each set of measurements, estimated fetal weights were obtained by a panel of 18 ultrasound weight formulae. The diagnosis of macrosomia was made if the fetal weight estimate was greater than 4500 g. Cohorts of 5000 pregnancies for each week of gestation were studied. The frequency of diagnosis of macrosomia increased progressively with advancing gestational age, with large increases between 40 and 41 weeks. The type of weight estimation formula had a profound influence on the frequency of diagnosis of macrosomia. Five of the formulae tested almost never returned a weight estimate greater than 4500 g. Three formulae yielded false positive rates in excess of 15%. The Hadlock group of formulae yielded frequencies of 0.3% to 14.6%. Most formulae tend to over-diagnose macrosomia at term. Intervention rates for suspected fetal macrosomia may be influenced by gestational age at the time of scan and the type of fetal weight estimation formula in use.


Investigation on chlorosomal antenna geometries: tube, lamella and spiral-type self-aggregates.
Molecular mechanics calculations and exciton theory have been used to study pigment organization in chlorosomes of green bacteria. Single and double rod, multiple concentric rod, lamella, and Archimedean spiral macrostructures of bacteriochlorophyll c molecules were created and their spectral properties evaluated. The effects of length, width, diameter, and curvature of the macrostructures as well as orientations of monomeric transition dipole moment vectors on the spectral properties of the aggregates were studied. Calculated absorption, linear dichroism, and polarization dependent fluorescence-excitation spectra of the studied long macrostructures were practically identical, but circular dichroism spectra turned out to be very sensitive to geometry and monomeric transition dipole moment orientations of the aggregates. The simulations for long multiple rod and spiral-type macrostructures, observed in recent high-resolution electron microscopy images (Oostergetel et al., FEBS Lett 581:5435-5439, 2007) gave shapes of circular dichroism spectra observed experimentally for chlorosomes. It was shown that the ratio of total circular dichroism intensity to integrated absorption of the Q(y) transition is a good measure of degree of tubular structures in the chlorosomes. Calculations suggest that the broad Q(y) line width of chlorosomes of sulfur bacteria could be due to (1) different orientations of the transition moment vectors in multi-walled rod structures or (2) a variety of Bchl-aggregate structures in the chlorosomes.


[14C]2-deoxyglucose demonstration of the organization of ocular dominance in areas 17 and 18 of the normal cat.
The purpose of this study was to demonstrate the spatial organization of ocular dominance in the visual cortex of the cat. We administered [14C]2-deoxyglucose ([14C]2-DG) to 4 alert, monocularly stimulated cats; one eye had previously been removed from 3 of these cats, and the other cat had received a uniocular injection of tetrodotoxin (TTX). In areas 17 and 18, but not in area 19, we observed alternating regions of heavy and light label, which were clearest in layer IV. Near the representation of the area centralis, especially in the hemisphere ipsilateral to the stimulated eye, the labeled regions formed columns that extended from the pial surface to the white matter. In the representation of peripheral retina, especially in the hemisphere contralateral to the stimulated eye, the pattern was often (but not always) restricted to the middle layers. We conclude that this pattern of label reflects the organization of ocular dominance because: (1) we never observed this pattern in control cats in which both eyes were stimulated or neither eye was stimulated; (2) many characteristics of the pattern are consistent with physiological studies of ocular dominance, and (3) the width and spacing of the alternating label was consistent with the size of the patches of geniculocortical afferents representing the left and right eyes in layer IV of areas 17 and 18.


CoT-XNet: contextual transformer with Xception network for diabetic retinopathy grading.
Objective.Diabetic retinopathy (DR) grading is primarily performed by assessing fundus images. Many types of lesions, such as microaneurysms, hemorrhages, and soft exudates, are available simultaneously in a single image. However, their sizes may be small, making it difficult to differentiate adjacent DR grades even using deep convolutional neural networks (CNNs). Recently, a vision transformer has shown comparable or even superior performance to CNNs, and it also learns different visual representations from CNNs. Inspired by this finding, we propose a two-path contextual transformer with Xception network (CoT-XNet) to improve the accuracy of DR grading.Approach.The representations learned by CoT through one path and those by the Xception network through another path are concatenated before the fully connected layer. Meanwhile, the dedicated pre-processing, data resampling, and test time augmentation strategies are implemented. The performance of CoT-XNet is evaluated in the publicly available datasets of DDR, APTOS2019, and EyePACS, which include over 50 000 images. Ablation experiments and comprehensive comparisons with various state-of-the-art (SOTA) models have also been performed.Main results.Our proposed CoT-XNet shows better performance than available SOTA models, and the accuracy and Kappa are 83.10% and 0.8496, 84.18% and 0.9000 and 84.10% and 0.7684 respectively, in the three datasets (listed above). Class activation maps of CoT and Xception networks are different and complementary in most images.Significance.By concatenating the different visual representations learned by CoT and Xception networks, CoT-XNet can accurately grade DR from fundus images and present good generalizability. CoT-XNet will promote the application of artificial intelligence-based systems in the DR screening of large-scale populations.


Correlation between handedness and birth order: compilation of five studies.
Bakan has suggested that left-handedness is the result of left hemishperic pyramidal motor dysfunction following perinatal hypoxia. To a degree support for the validity of this hypothesis rests on Bakan's (1971, 1977a) findings that left-handed college students were more likely the progeny of birth orders designated as "high-risk" than right-handed students. Attempts by others to replicate Bakan's data have been unsuccessful. To achieve a more powerful test of this relationship than has been provided by any single study, the data from the five studies which have considered it were pooled and tested. The resulting correlation between birth order and handedness was near zero.


Molecular cloning and nucleotide sequence of the genome of hog cholera virus.
A cDNA clone derived from genomic RNA of hog cholera virus (HCV) was identified using an oligonucleotide complementary to the RNA encoding a hexapeptide from the putative RNA-dependent RNA polymerase of the closely related bovine viral diarrhea virus (BVDV). This clone served as a probe for screening different size-selected cDNA libraries. After molecular cloning and nucleotide sequencing the HCV genome was shown to consist of 12,284 nucleotides containing one long open reading frame. Sequence comparison revealed a high degree of homology between HCV and BVDV genomic RNAs. With respect to HCV the genome of BVDV contains an insertion coding for 90 amino acids.


Dietary restriction amplifies the metabolic disturbances of very-low-density lipoproteins in cholesterol-fed rabbits.
The effect of dietary restriction (half of the control ration) on VLDL turnover was investigated in cholesterol-fed rabbits. Rabbits on standard, cholesterol and restricted cholesterol diets were injected with homologous 125I-labelled VLDL. Accompanying the amplification of hypercholesterolemia, additional disturbances of VLDL turnover were observed when cholesterol feeding was associated with dietary restriction. Cholesterol-fed rabbits with normal caloric ration exhibited delayed clearance of 125I-labelled apolipoprotein B component of VLDL compared to control rabbits. This was markedly accentuated in underfed rabbits, indicating further down-regulation of apolipoprotein B,E receptors in these animals. Furthermore, a reduced proportion of radiolabelled apolipoprotein B was converted from VLDL to intermediate-density lipoprotein (IDL) and LDL in both groups receiving cholesterol-rich diets. Thus, the combination of further impairment in plasma clearance of VLDL and the poor conversion into IDL and LDL could account for the massive increase of beta-VLDL in underfed animals on cholesterol-rich diets.


Rats treated chronically with the benzodiazepine, diazepam or with ethanol exhibit reduced variability of behavior.
The hypothesis that chronic treatment with diazepam or with ethanol reduces behavioral variability, was tested on rats in a radial maze. Eight groups (n = 6) of male Sprague-Dawley rats were given one of eight treatments of diazepam (0.0, 1.5, 3.0 or 6.0 mg/kg, IP, -30 min) or of 10% ethanol (0.0, 1.0, 1.5, or 2.0 g/kg, IP, -15 min) for 2 sessions of baseline and 18 sessions of acquisition. Each session consisted of 3 trials of 8 rewards each. Emptied food wells were immediately rebaited so that an entry into any arm produced a reward of 2 food pellets. Both diazepam and ethanol produced a dose-dependent reduction in the variability of arm choice, reduction in the variability of angle of turn between arms, and reduction in the variability of goal-directed behavior. Correlations between these measures suggested they were not independent. The implications of these reductions in behavioral variability for other effects of anxiolytic drugs are described.


Use of Smart Toe(©) implant for small toe arthrodesis: A smart concept?
Arthrodesis of small joints for hammer and claw toe deformities is a common forefoot operative procedure. Our objective was to review patients who underwent small toe arthrodesis with Smart Toe(©) intramedullary monobloc implant. Our aim was to assess patient's surgical outcome and to ascertain implant suitability. This procedure was undertaken in 90 patients from February 2011 to December 2012. We present our review of 82 (91.1%) patients who attended the final six 6-month follow up. Mean age was 56.5 years. There were 7 (8.5%) males and 75 (8.5%) males and 75 (91.5%) females. Clinical and radiological evaluation was undertaken. A questionnaire was used to assess general symptoms, clinical outlook, deformity and patient's perceptions and acceptance. Foot and Ankle Outcome Score and Foot and Ankle Disability Index were used to judge outcome. There were 71 (86.6%) proximal and 11 (13.4%) distal interphalangeal joints with 69 (84.1%) second, 7 (8.5%) third, 6 (84.1%) second, 7 (8.5%) third, 6 (7.3%) fourth toes. There was persistent swelling in 7 (8.5%) and tenderness in 1 (1.2%). Appearance of toes was symmetrical in 71 (86.6%) and 11 (13.4%) were asymmetrical but asymptomatic. The mean range of movement of the adjacent joint was 53.9°. Control of toes was good in 72 (87.8%) patients. Mean percentage of improvement was 76.1% with 100% in 17 (20.7%) and over 80% in 47 (57.3%). Seventy (85.3%) would recommend and undergo repeat surgery. There were 2 (2.4%) cases of metal cut out. There was one (1.2%) implant failure. Union was achieved in 79 (96.3%) patients. We feel that Smart Toe(©) small toe arthrodesis is a safe and reliable technique with good patient outcome and acceptance.


Effect of comprehensive geriatric assessment for frail elderly patients operated for colorectal cancer-the colorectal cancer frailty study: study protocol for a randomized, controlled, multicentre trial.
Colorectal cancer (CRC) is the third most common cancer worldwide, with a median age of 72-75 years at diagnosis. Curative treatment usually involves surgery; if left untreated, symptoms may require emergency surgery. Therefore, most patients will be accepted for surgery, despite of high age or comorbidity. It is known that elderly patients suffer higher risks after surgery than younger patients, in terms of complications and mortality. Assessing frailty and offering frail elderly patients individualized treatment according to the comprehensive geriatric assessment (CGA) and care concept has been shown to improve the outcome for frail elderly patients in other clinical contexts. This randomized controlled multicentre trial aims to investigate if CGA and care prior to curatively intended surgery for CRC in frail elderly patients will improve postoperative outcome. All patients ≥ 70 years with surgically curable CRC will be screened for frailty using the Clinical Frailty Scale (CFS-9). Frail patients will be offered inclusion. Randomization is stratified for colon or rectal cancer. Patients in the intervention group are, in addition to standard protocol, treated according to CGA and care. This consists of individualized assessments and interventions, established by a multiprofessional team. Patients in the control group are treated according to best known practice as stipulated by Swedish colorectal cancer treatment guidelines, within an enhanced recovery after surgery (ERAS) setting. The primary outcome is 90-day mortality. Secondary outcomes are the length of hospital stay and total number of hospital days within 3 months, discharge destination, 30-day readmission, ADL, safe medication assessment, CFS-9 score, complications, Health-Related Quality of Life (HRQoL) at 2-month follow-up in comparison to baseline measurements, health economical calculations including cost-effectiveness analysis based on costs of hospital care and primary care, mortality and HRQoL at baseline, 2- and 12-month follow-up and all-cause 1-year mortality. The trial is the first of its size and extent to investigate intervention with CGA and care prior to surgery for CRC in frail elderly patients. If this addition proves to be favourable, it could have implications on future care of frail elderly patients with CRC. ClinicalTrials.gov NCT04358328. Registered on 4 February 2020.


Fetal distress associated with the anticardiolipin antibody and a history of intrauterine fetal demise. A case report.
A woman with a history of fetal demise, an elevated anticardiolipin antibody titer, lupus anticoagulant but no evidence of systemic lupus erythematosus received anticoagulation with heparin in adjusted subcutaneous doses. Daily fetal monitoring demonstrated reactive nonstress tests and normal biophysical profiles initially. At 30 weeks' gestation, however, repeated spontaneous decelerations developed, and fetal bradycardia necessitated delivery. The combination of a poor obstetric history and the presence of high cardiolipin antibody titers requires close fetal surveillance. The benefits of anticoagulation in this setting deserve further study.


The challenges of defining hormesis in epidemiological studies: The case of radiation hormesis.
In the current radiation protection system, preventive measures and occupational exposure limits for controlling occupational exposure to ionizing radiation are based on the linear no-threshold extrapolation model. However, currently an increasing body of evidence indicates that this paradigm predicts very poorly biological responses in the low-dose exposure region. In addition, several in vitro and in vivo studies demonstrated the presence of hormetic dose response curves correlated to ionizing radiation low exposure. In this regard, it is noteworthy that also the findings of different epidemiological studies, conducted in different categories of occupationally exposed workers (e.g., healthcare, nuclear industrial and aircrew workers), observed lower rates of mortality and/or morbidity from cancer and/or other diseases in exposed workers than in unexposed ones or in the general population, then suggesting the possible occurrence of hormesis. Nevertheless, these results should be considered with caution since the identification of hormetic response in epidemiological studies is rather challenging because of a number of major limitations. In this regard, some of the most remarkable shortcomings found in epidemiological studies performed in workers exposed to ionizing radiation are represented by lack or inadequate definition of exposure doses, use of surrogates of exposure, narrow dose ranges, lack of proper control groups and poor evaluation of confounding factors. Therefore, considering the valuable role and contribution that epidemiological studies might provide to the complex risk assessment and management process, there is a clear and urgent need to overcome the aforementioned limits in order to achieve an adequate, useful and more real-life risk assessment that should also include the key concept of hormesis. Thus, in the present conceptual article we also discuss and provide possible approaches to improve the capacity of epidemiological studies to identify/define the hormetic response and consequently improve the complex process of risk assessment of ionizing radiation at low exposure doses.


Decidual cell regulation of natural killer cell-recruiting chemokines: implications for the pathogenesis and prediction of preeclampsia.
First trimester human decidua is composed of decidual cells, CD56(bright)CD16(-) decidual natural killer (dNK) cells, and macrophages. Decidual cells incubated with NK cell-derived IFN-γ and either macrophage-derived TNF-α or IL-1β synergistically enhanced mRNA and protein expression of IP-10 and I-TAC. Both chemokines recruit CXCR3-expressing NK cells. This synergy required IFN-γ receptor 1 and 2 mediation via JAK/STAT and NFκB signaling pathways. However, synergy was not observed on neutrophil, monocyte, and NK cell-recruiting chemokines. Immunostaining of first trimester decidua localized IP-10, I-TAC, IFN-γR1, and -R2 to vimentin-positive decidual cells versus cytokeratin-positive interstitial trophoblasts. Flow cytometry identified high CXCR3 levels on dNK cells and minority peripheral CD56(bright)CD16(-) pNK cells and intermediate CXCR3 levels on the majority of CD56(dim)CD16(+) pNK cells. Incubation of pNK cells with either IP-10 or I-TAC elicited concentration-dependent enhanced CXCR3 levels and migration of both pNK cell subsets that peaked at 10 ng/mL, whereas each chemokine at a concentration of 50 ng/mL inhibited CXCR3 expression and pNK cell migration. Deciduae from women with preeclampsia, a leading cause of maternal and fetal morbidity and mortality, displayed significantly lower dNK cell numbers and higher IP-10 and I-TAC levels versus gestational age-matched controls. Significantly elevated IP-10 levels in first trimester sera from women eventually developing preeclampsia compared with controls, identifying IP-10 as a novel, robust early predictor of preeclampsia.


Optical-resolution photoacoustic microscopy: auscultation of biological systems at the cellular level.
Photoacoustic microscopy (PAM) offers unprecedented sensitivity to optical absorption and opens a new window to study biological systems at multiple length- and timescales. In particular, optical-resolution PAM (OR-PAM) has pushed the technical envelope to submicron length scales and millisecond timescales. Here, we review the state of the art of OR-PAM in biophysical research. With properly chosen optical wavelengths, OR-PAM can spectrally differentiate a variety of endogenous and exogenous chromophores, unveiling the anatomical, functional, metabolic, and molecular information of biological systems. Newly uncovered contrast mechanisms of linear dichroism and Förster resonance energy transfer further distinguish OR-PAM. Integrating multiple contrasts and advanced scanning mechanisms has capacitated OR-PAM to comprehensively interrogate biological systems at the cellular level in real time. Two future directions are discussed, where OR-PAM holds the potential to translate basic biophysical research into clinical healthcare.


Influence of mixing and ultrasound frequency on antisolvent crystallisation of sodium chloride.
Ultrasound is known to promote nucleation of crystals and produce a narrower size distribution in a controlled and reproducible manner for the crystallisation process. Although there are various theories that suggest cavitation bubbles are responsible for sonocrystallisation, most studies use power ultrasonic horns that generate both intense shear and cavitation and this can mask the role that cavitation bubbles play. High frequency ultrasound from a plate transducer can be used to examine the effect of cavitation bubbles without the intense shear effect. This study reports the crystal size and morphology with various mixing speeds and ultrasound frequencies. The results show high frequency ultrasound produced sodium chloride crystals of similar size distribution as an ultrasonic horn. In addition, ultrasound generated sodium chloride crystals having a more symmetrical cubic structure compared to crystals produced by a high shear mixer.


Corrigendum: Interference With Coagulation Cascade as a Novel Approach to Counteract Cisplatin-Induced Acute Tubular Necrosis; an Experimental Study in Rats.
[This corrects the article DOI: 10.3389/fphar.2018.01155.].