The increased transglutaminase 2 expression levels during initial tumorigenesis predict increased risk of metastasis and decreased disease-free and cancer-specific survivals in renal cell carcinoma.
The aim of this study was to investigate the role of transglutaminase 2(TG2) in renal cell carcinoma (RCC) by comparing the immunohistochemistry staining of primary and metastatic tumor tissues. A total of 33 metastatic RCC(mRCC) and 33 non-metastatic RCC (nmRCC) patients who were matched as closely as possible based on gender, age, nuclear grade and pathologic T stage were retrospectively investigated. TG2 immunohistochemistry staining was performed on paraffin-embedded primary tumor tissues from both patient groups and on metastatic tissues from mRCC patients. The tissues were scored from 0 to 7 according to the TG2 staining. Furthermore, the patients were stratified into two groups using median primary tumor staining score as the cutoff value: Group 1 (high risk, n = 41) and Group 2(low risk, n = 22). The clinical, histopathological and survival outcomes were compared between these risk groups using Chi-square test, t test, Mann-Whitney U test and Kaplan-Meier survival analyses. The median TG2 score for primary tumor was 5 for the entire study population. The median primary tumor TG2 score of the mRCC patients was significantly higher compared to the nmRCC patients (6 vs. 4, p < 0.001). The TG2 score between the primary and metastatic tissues of mRCC patients was not significantly different (6 vs. 7, p = 0.086). The percentage of metastatic patients was significantly higher in Group 1 compared to Group 2 (68.3 vs. 18.2 %, p < 0.001). Kaplan-Meier analyses showed that 5-year disease-free (34.9 vs. 92.9 %, p = 0.001) and cancer-specific (47.4 vs. 86.5 %, p = 0.04) survival rates were significantly lower in high-risk group. The increased expression of TG2 in primary tumor predicts metastasis in RCC patients and is also associated with a decrease in disease-free and cancer-specific survival outcomes.


The relationship between number of primary health care visits and hospitalisations: evidence from linked clinic and hospital data for remote Indigenous Australians.
Primary health care (PHC) is widely regarded as essential for preventing and treating ill health. However, the evidence on whether improved PHC reduces hospitalisations has been mixed. This study examines the relationship between PHC and hospital inpatient care in a population with high health need, high rates of hospitalisation and relatively poor PHC access. The cross-sectional study used linked individual level PHC visit and hospitalisation data for 52 739 Indigenous residents from 54 remote communities in the Northern Territory of Australia between 1 July 2007 and 30 June 2011. The association between PHC visits and hospitalisations was modelled using simple and spline quadratic regression for key demographics and disease groups including potentially avoidable hospitalisations. At the aggregate level, the average annual number of PHC visits per person had a U-shaped association with hospitalisations. For all conditions combined, there was an inverse association between PHC visits and hospitalisations for people with less than four clinic visits per year, but a positive association for those visiting the clinic four times or more. For patients with diabetes, ischaemic heart disease or renal disease, the minimum level of hospitalisation was found when there was 20-30 PHC visits a year, and for children with otitis media and dental conditions, 5-8 visits a year. The results of this study demonstrate a U-shape relationship between PHC visits and hospitalisations. Under the conditions of remote Indigenous Australians, there may be an optimal level of PHC at which hospitalisations are at a minimum. The authors propose that the effectiveness of a health system may hinge on a refined balance, rather than a straight-line relationship between primary health care and tertiary care.


Kahook Dual-Blade Goniotomy with and without Phacoemulsification in Medically Uncontrolled Glaucoma.
To evaluate the 2-year efficacy and safety of Kahook dual-blade (KDB) goniotomy in patients with medically uncontrolled glaucoma. This was a retrospective case-series study of 90 consecutive patients with primary open-angle glaucoma (POAG) or pseudoexfoliation glaucoma (PEXG) that underwent KDB goniotomy alone (KDB-alone group) or KDB goniotomy in combination with phacoemulsification (KDB-phaco group) during 2019-2020. All patients were uncontrolled on three or more medications. Surgical success was defined as an IOP reduction ≥20% and/or a reduction of one or more medications at 24 months. We also report IOP levels and number of medications from baseline to 24 months, as well as the need for further glaucoma interventions. At 24 months, mean IOP had reduced from 24.8±8.3 to 15.0±5.3 mmHg in the KDB-alone group (P<0.001) and from 22.3±5.8 to 13.9±3.0 mmHg in the KDB-phaco group (P<0.001). Medications had reduced from 3.5±0.6 to 3.1±0.9 in the KDB-alone group (P=0.047) and from 3.3±0.5 to 2.3±1.1 in the KDB-phaco group (P<0.001). An IOP reduction ≥20% and/or a reduction with one or more medications was achieved by 47% of eyes in the KDB-alone group and by 76% of eyes in the KDB-phaco group. Eyes with PEXG and POAG responded equally well to the success criteria. During the 24-month follow-up, additional glaucoma surgery or transscleral photocoagulation was performed in 28% of eyes in the KDB-alone group and in 12% of eyes in the KDB-phaco group. In patients with medically uncontrolled glaucoma, KDB had a significant IOP-lowering effect after 24 months, but success rates were higher when KDB was performed in combination with cataract surgery compared to stand-alone treatment.


Interobserver reliability in the interpretation of computed tomographic scans of stroke patients.
Interobserver reliability in interpretation of computed tomographic images was studied by six senior neurologists who independently evaluated on a standardized Stroke Data Bank form the brain lesions of 17 patients. The results analyzed with kappa statistics yielded moderate to substantial agreement on most items of interest including the stroke pathology and anatomy. In general, the levels of agreement were as high as previously reported for the diagnosis of the mechanism of the stroke, and much higher than on many stroke history items and items of neurologic examination. Excellent agreement was obtained for the detection of infarcts and intracerebral hemorrhage, and substantial agreement was obtained on whether the computed tomographic images were normal or indicative of small deep infarcts, superficial and deep infarcts, and aneurysms. The level of agreement on anatomy of the lesions was best for the frontal, parietal, and temporal lobes, putamen, cerebellum, and subarachnoid space. Implications for clinical research and diagnosis are discussed.


Degradation of Polyamide Membranes Exposed to Chlorine: An Impedance Spectroscopy Study.
Polyamide is the key material in modern membrane desalination; however, its well-known and incompletely understood drawback is its low tolerance to chlorine, the most efficient in-line disinfectant. Here we report a first investigation of the mechanism and kinetics of chlorine attack using electrochemical impedance spectroscopy (EIS) that directly probes changes in ion permeation upon chlorination at different pH values, focusing on its early stages and low chlorine concentrations (15-197 ppm). EIS results partly conform to an established two-stage mechanism that proceeds as N-chlorination followed by either C-chlorination in acidic conditions or amide bond scission in alkaline conditions. However, early time kinetics in acidic conditions shows inconsistencies with this model, explained by possible effects of direct ring chlorination and finite polymer relaxation rates. The findings indicate that (a) N-chlorination reduces membrane polarity and ion permeability, while C-chlorination has an opposite effect; (b) chlorination in acidic conditions must involve other reactions, such as direct ring chlorination, in addition to N-chlorination and Orton rearrangement; and (c) the ultimate chemical transformations (C-chlorination or amide bond scission) result in an irreversible increase in membrane polarity and loss of ion rejection. The results highlight the potential of EIS as a powerful and sensitive tool for studying chemical degradation of ion-selective materials that may assist in developing new chlorine-resistant membranes.


[The experience of administration of 15-deoxyspergualin on rejection in kidney transplant recipients].
We report here the favorable results of clinical application of 15-deoxyspergualin (DSG) as a rescue therapy for rejection episodes in kidney transplant recipients. DSG was discovered in Japan and was proved to be a novel immunosuppressant in various animal transplantation models. The immunosuppressive mechanism of DSG is unclear yet, but its point of action is supposed to be in the early immuno response to allogeneic stimulation without the regulation of cytokine production. We performed the administration of DSG in fifteen patients, who had rejection episodes, with a dosage of 3 mg/kg/day or 5 mg/kg/day for five days by drip infusion. In the group of recipients who had rejection episodes within six months after kidney transplantation, DSG proved effective on six out of seven acute rejection episodes and induced favorable remission. And in the group of recipients who had rejection episodes after six months since kidney transplantation, DSG proved effective on all of ten rejection episodes. There was not a difference of effectiveness in respect to the dosage of DSG. The side effect of DSG treatment was mainly leukopenia but in most cases these leukopenia was remitted just under careful observation. Some patients complained the sense of abdominal discomfort. But so far, we did not encounter serious or critical side effects and complications during all the time of progression. Another benefit was that DSG was able to reverse the rejection episode even in the patient who had already treated with anti lymphocyte globulin and/or anti CD3 monoclonal antibody OKT3. We concluded that the administration of DSG as a rescue therapy was not accompanied by the serious side effects and was most effective against acute rejection after kidney transplantation.


Control of microenvironment around enzymes by hydrogels.
We prepared enzyme-immobilized hydrogels and investigated the effects of the cross-linking density and polymer properties on their oxidation reaction rate. The oxidation rate of enzyme-immobilized hydrogels increased as the cross-linking density in the hydrogels increased. In addition, we controlled the oxidation rate using hydrogels exhibiting an appropriate interaction with a decoy molecule in the hydrogel.


Colony-stimulating factors for chemotherapy-induced febrile neutropenia.
Febrile neutropenia is a frequent adverse event experienced by people with cancer who are undergoing chemotherapy, and is a potentially life-threatening situation. The current treatment is supportive care plus antibiotics. Colony-stimulating factors (CSFs), such as granulocyte-CSF (G-CSF) and granulocyte-macrophage CSF (GM-CSF), are cytokines that stimulate and accelerate the production of one or more cell lines in the bone marrow. Clinical trials have addressed the question of whether the addition of a CSF to antibiotics could improve outcomes in individuals diagnosed with febrile neutropenia. However, the results of these trials are conflicting. To evaluate the safety and efficacy of adding G-CSF or GM-CSF to standard treatment (antibiotics) when treating chemotherapy-induced febrile neutropenia in individuals diagnosed with cancer. We conducted the search in March 2014 and covered the major electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, and SCI. We contacted experts in hematology and oncology and also scanned the citations from the relevant articles. We searched for randomized controlled trials (RCTs) that compared CSF plus antibiotics versus antibiotics alone for the treatment of chemotherapy-induced febrile neutropenia in adults and children. We used the standard methodological procedures expected by The Cochrane Collaboration. We performed meta-analysis of the selected studies using Review Manager 5 software. Fourteen RCTs (15 comparisons) including a total of 1553 participants addressing the role of CSF plus antibiotics in febrile neutropenia were included. Overall mortality was not improved by the use of CSF plus antibiotics versus antibiotics alone (hazard ratio (HR) 0.74 (95% confidence interval (CI) 0.47 to 1.16) P = 0.19; 13 RCTs; 1335 participants; low quality evidence). A similar finding was seen for infection-related mortality (HR 0.75 (95% CI 0.47 to 1.20) P = 0.23; 10 RCTs; 897 participants; low quality evidence). Individuals who received CSF plus antibiotics were less likely to be hospitalized for more than 10 days (risk ratio (RR) 0.65 (95% CI 0.44 to 0.95) P = 0.03; 8 RCTs; 1221 participants; low quality evidence) and had more number of participants with a more faster neutrophil recovery (RR 0.52 (95% CI 0.34 to 0.81) P = 0.004; 5 RCTs; 794 participants; moderate quality evidence) than those treated with antibiotics alone. Similarly, participants receiving CSF plus antibiotics had shorter duration of neutropenia (standardized mean difference (SMD) -1.70 (95% CI -2.65 to -0.76) P = 0.0004; 9 RCTs; 1135 participants; moderate quality evidence), faster recovery from fever (SMD -0.49 (95% CI -0.90 to -0.09) P value = 0.02; 9 RCTs; 966 participants; moderate quality evidence) and shorter duration of antibiotics use (SMD -1.50 (95% CI -2.83 to -0.18) P = 0.03; 3 RCTs; 457 participants; low quality evidence) compared with participants receiving antibiotics alone. We found no significant difference in the incidence of deep venous thromboembolism (RR 1.68 (95% CI 0.72 to 3.93) P = 0.23; 4 RCTs; 389 participants; low quality evidence) in individuals treated with CSF plus antibiotics compared with those treated with antibiotics alone. We found higher incidence of bone or joint pain or flu-like symptoms (RR 1.59 (95% CI 1.04 to 2.42) P = 0.03; 6 RCTs; 622 participants; low quality evidence) in individuals treated with CSF plus antibiotics compared with those treated with antibiotics alone. Overall, the methodological quality of studies was moderate to low across different outcomes. The main reasons to downgrade the quality of evidence were inconsistency across the included studies and imprecision of results. The use of a CSF plus antibiotics in individuals with chemotherapy-induced febrile neutropenia had no effect on overall mortality, but reduced the amount of time participants spent in hospital and improved their ability to achieve neutrophil recovery. It was not clear whether CSF plus antibiotics had an effect on infection-related mortality. Participants receiving CSFs had shorter duration of neutropenia, faster recovery from fever and shorter duration of antibiotics use.


A Clinical Prediction Model to Assess Risk for Pancreatic Cancer Among Patients With New-Onset Diabetes.
Approximately 50% of all patients with pancreatic ductal adenocarcinoma (PDA) develop diabetes mellitus before their cancer diagnosis. Screening individuals with new-onset diabetes might allow earlier diagnosis of PDA. We sought to develop and validate a PDA risk prediction model to identify high-risk individuals among those with new-onset diabetes. We conducted a retrospective cohort study in a population representative database from the United Kingdom. Individuals with incident diabetes after the age of 35 years and 3 or more years of follow-up after diagnosis of diabetes were eligible for inclusion. Candidate predictors consisted of epidemiologic and clinical characteristics available at the time of diabetes diagnosis. Variables with P values <.25 in the univariable analyses were evaluated using backward stepwise approach. Model discrimination was assessed using receiver operating characteristic curve analysis. Calibration was evaluated using the Hosmer-Lemeshow test. Results were internally validated using a bootstrapping procedure. We analyzed data from 109,385 patients with new-onset diabetes. Among them, 390 (0.4%) were diagnosed with PDA within 3 years. The final model (area under the curve, 0.82; 95% confidence interval, 0.75-0.89) included age, body mass index, change in body mass index, smoking, use of proton pump inhibitors, and anti-diabetic medications, as well as levels of hemoglobin A1C, cholesterol, hemoglobin, creatinine, and alkaline phosphatase. Bootstrapping validation showed negligible optimism. If the predicted risk threshold for definitive PDA screening was set at 1% over 3 years, only 6.19% of the new-onset diabetes population would undergo definitive screening, which would identify patients with PDA with 44.7% sensitivity, 94.0% specificity, and a positive predictive value of 2.6%. We developed a risk model based on widely available clinical parameters to help identify patients with new-onset diabetes who might benefit from PDA screening.


[Pregnancy, acquired immunity and parasitic diseases: main mechanisms associated to resistance or susceptibility].
During pregnancy in mammals, the endocrine system plays a protagonic role, characterized by variation of different hormonal serum levels, such as estradiol, progesterone and some gonadotrophic hormones. Furthermore, the immunological system also participates during pregnancy, self-regulation for to avoid not rejecting the fetus. The characteristic immunity during the pregnancy is the humoral type: which is characterized by an increase in the levels of the Th-2 type cytokines IL-4, IL-6, IL-10, concomitant to a diminution in the levels of IL-2, INF-gamma and TNF-alpha The type of immunological response present during the pregnancy is mainly regulated by mechanisms associated to sexual hormones. This particular immunological response during the pregnancy, has individual importance if an infectious disease appears, since, depending on the parasite, a susceptibility or a resistance to the infection can exist. The proposed mechanisms to explain this resistance or susceptibility can be one of the following: (1) the hormones are influencing the immunological system of the host (by means of specific nuclear receptors); (2) the hormones acting directly on the parasite, preventing or promoting their reproduction and (3) a combination of both. These mechanisms support the idea of a complex immunoendocrine network (mediated by hormonal receptors, citokynes, antibodies) in host and parasite, interacting in a bidirectional way. The final outcome of this interaction is the death or survival of the host, or the parasite. In this review, we evaluate the information about the more frequent parasitic infections during pregnancy, and discuss the implied molecular mechanisms that affects the establishment, growth, reproduction or elimination of the parasite.


When is breeding for drought tolerance optimal if drought is random?
* Increasing climatic unpredictability associated with characteristics of some species makes plant drought-tolerance an important drought-adaptation strategy. Using norm-of-reaction functions, or empirically determined functions that enable us to predict the state of a trait given the state of an environmental variable, allows modelling of plant performance when water availability varies randomly. * A mathematical model is proposed to evaluate drought-tolerance and growth strategies given a set of environmental parameters: the frequency of rainy days, the soil water-storage capacity, plant water use and plant growth rates. This model compares the performance of genotypes that differ in drought tolerance expressed as the ability to grow in drier soils, and assumes a general trade-off function between drought tolerance and maximum plant growth rate. * It is worth selecting plants with a greater degree of drought tolerance, expressed by the ability to grow in drier soils whenever the frequency of rains is smaller than the rate of soil water depletion. Otherwise, maximizing growth rate at the expense of drought tolerance is the best strategy. The nature of the trade-off between drought tolerance and plant growth rate also constrains the selection for optimal drought-adapted genotypes. * Breeders will have to consider these aspects of plant-environment interactions before establishing selection programs for drought adaptation.


[Individual psychotherapy--family therapy in children and adolescents].
The theoretical basis, the therapeutical approach and the methods of individual psychotherapy and of family therapy are presented. Possibilities and limitations, advantages and disadvantages of the two forms of therapy are discussed and illustrated by means of case histories. It is pointed out that the question of indication can only be solved if on the one hand the patient "individual" and the patient "family" are considered, and if the therapist with his theoretical and practical possibilities is included on the other hand.


Normal cutaneous sensibility of the breast.
A total of 150 healthy women were studied to determine normal values for breast sensibility and to investigate the influence of breast size and ptosis on breast sensation. Cutaneous pressure thresholds were evaluated bilaterally in six areas including the nipple, the areola, and the skin of the breast using the Semmes-Weinstein monofilaments. We found that the skin of the superior quadrant was the most sensitive part of the breast, the areola was less sensitive, and the nipple was the least sensitive part. The cutaneous sensibility of all tested areas decreased significantly with increasing breast size and increasing breast ptosis. The nipple was less sensitive in women who had a previous pregnancy. Age, smoking history, or hormonal contraception had no significant influence on breast sensation. The study shows that the Semmes-Weinstein test is an adequate method for assessing sensation in the breast.


Fostering social innovation and building adaptive capacity for dengue control in Cambodia: a case study.
The social-ecological systems theory, with its unique conception of resilience (social-ecological systems & resilience, SESR), provides an operational framework that currently best meets the need for integration and adaptive governance as encouraged by the Sustainable Development Goals. SESR accounts for the complex dynamics of social-ecological systems and operationalizes transdisciplinarity by focusing on community engagement, value co-creation, decentralized leadership and social innovation. Targeting Social Innovation (SI) in the context of implementation research for vector-borne diseases (VBD) control offers a low-cost strategy to contribute to lasting and contextualized community engagement in disease control and health development in low and middle income countries of the global south. In this article we describe the processes of community engagement and transdisciplinary collaboration underpinning community-based dengue management in rural primary schools and households in two districts in Cambodia. Multiple student-led and community-based interventions have been implemented focusing on empowering education, communication for behavioral change and participatory epidemiology mapping in order to engage Cambodian communities in dengue control. We describe in particular the significance of the participatory processes that have contributed to the design of SI products that emerged following iterative consultations with community stakeholders to address the dengue problem. The SI products that emerged following our interaction with community members are 1) adult mosquito traps made locally from solid waste collections, 2) revised dengue curriculum with hands-on activities for transformative learning, 3) guppy distribution systems led by community members, 4) co-design of dengue prevention communication material by students and community members, 5) community mapping. The initiative described in this article put in motion processes of community engagement towards creating ownership of dengue control interventions tools by community stakeholders, including school children. While the project is ongoing, the project's interventions so far implemented have contributed to the emergence of culturally relevant SI products and provided initial clues regarding 1) the conditions allowing SI to emerge, 2) specific mechanisms by which it happens and 3) how external parties can facilitate SI emergence. Overall there seems to be a strong argument to be made in supporting SI as a desirable outcome of project implementation towards building adaptive capacity and resilience and to use the protocol supporting this project implementation as an operational guiding document for other VBD adaptive management in the region.


An antisense construct of full-length human RAD50 cDNA confers sensitivity to ionizing radiation and alkylating agents on human cell lines.
In Saccharomyces cerevisiae, Rad50 is reported to participate in the repair of double-stranded DNA breaks, and most rad50 mutants are unable to repair gamma-ray-induced DNA damage. In this study, we examined whether human RAD50 is involved in the repair of DNA damage induced by gamma radiation, radiomimetic alkylating agents, or UVB radiation in cultured human cells. Because homozygous null RAD50 mutant cells could not be isolated, human 293 embryonic kidney cells and A431 epithelial tumor cells were transfected with antisense RAD50 cDNA to obtain viable cell lines which expressed reduced RAD50. Selected individual clones were subjected to PCR-Southern and Western blot analyses to confirm the integrity of the antisense RAD50 construct and the reduced RAD50 expression levels. The cells engineered to express reduced RAD50 levels showed significantly increased sensitivity to gamma radiation, mitomycin C and methylmethane sulfonate compared with control cells that were transfected with the vector alone. However, there were no differences in viability of cells with reduced RAD50 levels and control cells treated with UVB radiation. These results indicate that human RAD50 is involved in the repair of DNA damage induced by gamma radiation and alkylating agents in mammalian cells and suggest the possible application of antisense RAD50 cDNA transfection as a radiation sensitizer in radiation oncology.


[A case of pulmonary barotrauma complicated with cerebral arterial air embolism in a diver].
Pulmonary barotrauma is a kind of disease caused by the injury of lung tissue or blood vessel when the gas pressure of lung is too high or too lower than the external pressure of the body, which causes the air to enter the blood vessel and adjacent tissue. It could be happened in the escape of the divers with the light diving equipment or the sailors from submarine. Generally, the decompression chamber was used to treating the disease, and the minimum air pressure of 0.5 MPa recompression therapeutic schedule was used to selecting. In November 2019, a patient with pulmonary barotrauma combined with cerebral arterial gas embolism caused by improper underwater escape with light diving equipment was admitted to the General Hospital of Eastern War Zone. He was treated with 0.12 MPa oxygen inhalation recompression scheme in the oxygen chamber pressurized with air. 7 days later, the patient recovered and discharged.


Direct Three-Dimensional Diagnosis of Ex Vivo Facial Fractures.
The aim of the present study is to assess the reliability and accuracy of different 3-dimensional (3D) reconstruction algorithms in detecting undisplaced condylar, zygomatic arc, and orbital rim fractures based on cone-beam computed tomography data set. Twenty sheep heads were used in the present study. Sixty fractured and 60 nonfractured (control) zones were randomly allocated. Three groups consisting of nondisplaced fractures of condyle (CF, n = 20), orbital (OF, n = 20), and zygomatic arc (ZF, n = 20) were created by using a diamond cutting disc. Soft tissues were only dissected and no fractures were generated in the control group (n = 60). The 3D reconstructions were created by using multiplanar reconstruction (MPR), surface rendering (SR), volume rendering (VR), and maximum intensity projection (MIP) algorithms. Final 3D models were examined in Osirix software (Pixmeo SARL, Bernex, Switzerland) by 6 observers. Diagnostic accuracies of each algorithm were statistically compared by receiver operating characteristics (ROC) and area under the ROC curves (AUCs). For the detection of CF, AUC for VR algorithm was found to be statistically larger than that of MIP while AUCs for VR and MIP were larger than those of MPR and SR for OF detection. For the detection of ZF, AUCs for MPR and VR were significantly larger than those of MIP and SR (P < 0.05 for each). Within the limitations of this experimental study, it can be concluded that for maxillofacial surgeons, it is more likely to detect condylar, orbital, and zygomatic fractures by using VR algorithm in 3D reconstruction.


Sensory drive in cichlid speciation.
The role of selection in speciation is a central yet poorly understood problem in evolutionary biology. The rapid radiations of extremely colorful cichlid fish in African lakes have fueled the hypothesis that sexual selection can drive species divergence without geographical isolation. Here we present experimental evidence for a mechanism by which sexual selection becomes divergent: in two sibling species from Lake Victoria, female mating preferences for red and blue male nuptial coloration coincide with their context-independent sensitivities to red and blue light, which in turn correspond to a difference in ambient light in the natural habitat of the species. These results suggest that natural selection on visual performance, favoring different visual properties in different spectral environments, may lead to divergent sexual selection on male nuptial coloration. This interplay of ecological and sexual selection along a light gradient may provide a mechanism of rapid speciation through divergent sensory drive.


The COVID-19 Pandemic Surge and Impact on Rheumatic Valvular Heart Disease Patient Care.
The COVID-19 crisis has surged worldwide, putting immense stress on the health care services, leading to institutions deferring elective procedures and struggling to triage the emergency care of cardiac patients. This has affected the management of the rheumatic valvular heart disease patients especially, in developing countries, potentially placing these patients at enormous risk for complications like congestive cardiac failure, stroke and death. This article explores the COVID-19 pandemic and its impact on rheumatic valvular heart disease patient care. We try to provide a framework that addresses the procedural considerations of interventions like percutaneous transluminal mitral commissurotomy (PTMC), mitral and aortic valve surgeries. This article also highlights the implications for the outpatient valve clinic, and safety issues of the patient and health care workers during this ongoing pandemic.


Virulence and resistance to superoxide, low pH and hydrogen peroxide among strains of Mycobacterium tuberculosis.
Six strains of Mycobacterium tuberculosis of different virulence in guinea-pigs were compared with regard to their resistance to low pH, to hydrogen peroxide (H2O2) at different pH values and to superoxide (O2-). Low virulence was associated with susceptibility to H2O2 in native and isoniazid-resistant strains but not in laboratory-attenuated strain H37Ra. H2O2 resistance was only partly related to catalase content. Low virulence was not associated with susceptibility to an acid environment but the tuberculocidal effect of H2O2 was significantly increased at low pH. The strains were uniformly resistant to O2- and contained similar amounts of superoxide dismutase. The implications of these observations are discussed in the context of mechanisms of host defence in tuberculosis.


Adaptive immune system in pulmonary sarcoidosis-Comparison of peripheral and alveolar biomarkers.
Sarcoidosis is a multi-systemic granulomatous disease of unknown origin. Recent research has focused upon the role of autoimmunity in its development and progression. This study aimed to determine and define the disturbance and distribution of T and B cell subsets in the alveolar and peripheral compartments. Thirteen patients were selected for the study [median age, interquartile range (IQR) = 57 years (48-59); 23% were male]. Twelve healthy controls [median age, IQR = 53 years (52-65); 16% male] were also enrolled into the study. Cellular and cytokine patterns were measured using the cytofluorimetric approach. Peripheral CD8 percentages were higher in sarcoidosis patients (SP) than healthy controls (HC) (p = 0.0293), while CD4 percentages were lower (p = 0.0305). SP showed low bronchoalveolar lavage (BAL) percentages of CD19 (p = 0.0004) and CD8 (p = 0.0035), while CD19+ CD5+ CD27- percentages were higher (p = 0.0213); the same was found for CD4 (p = 0.0396), follicular regulatory T cells (Treg ) (p = 0.0078) and Treg (p < 0.0001) cells. Low T helper type 17 (Th17) percentages were observed in BAL (p = 0.0063) of SP. Peripheral CD4+ C-X-C chemokine receptor (CXCR)5+ CD45RA- ) percentages and follicular T helper cells (Tfh)-like Th1 (Tfh1) percentages (p = 0.0493 and p = 0.0305, respectively) were higher in the SP than HC. Tfh1 percentages and Tfh-like Th2 percentages were lower in BAL than in peripheral blood (p = 0.0370 and p = 0.0078, respectively), while CD4+ C-X-C motif CXCR5+ CD45RA- percentages were higher (p = 0.0011). This is the first study, to our knowledge, to demonstrate a link between an imbalance in circulating and alveolar Tfh cells, especially CCR4-, CXCR3- and CXCR5-expressing Tfh subsets in the development of sarcoidosis. These findings raise questions about the pathogenesis of sarcoidosis and may provide new directions for future clinical studies and treatment strategies.


Probing RNA recognition by human ADAR2 using a high-throughput mutagenesis method.
Adenosine deamination is one of the most prevalent post-transcriptional modifications in mRNA. In humans, ADAR1 and ADAR2 catalyze this modification and their malfunction correlates with disease. Recently our laboratory reported crystal structures of the human ADAR2 deaminase domain bound to duplex RNA revealing a protein loop that binds the RNA on the 5' side of the modification site. This 5' binding loop appears to be one contributor to substrate specificity differences between ADAR family members. In this study, we endeavored to reveal detailed structure-activity relationships in this loop to advance our understanding of RNA recognition by ADAR2. To achieve this goal, we established a high-throughput mutagenesis approach which allows rapid screening of ADAR variants in single yeast cells and provides quantitative evaluation for enzymatic activity. Using this approach, we determined the importance of specific amino acids at 19 different positions in the ADAR2 5' binding loop and revealed six residues that provide essential structural elements supporting the fold of the loop and key RNA-binding functional groups. This work provided new insight into RNA recognition by ADAR2 and established a new tool for defining structure-function relationships in ADAR reactions.


Neuromuscular prehabilitation to prevent osteoarthritis after a traumatic joint injury.
Post-traumatic osteoarthritis (PTOA) is a process resulting from direct forces applied to a joint that cause injury and degenerative changes. An estimated 12% of all symptomatic osteoarthritis (OA) of the hip, knee, and ankle can be attributed to a post-traumatic cause. Neuromuscular prehabilitation is the process of improving neuromuscular function to prevent development of PTOA after an initial traumatic joint injury. Prehabilitation strategies include restoration of normative movement patterns that have been altered as the result of traumatic injury, along with neuromuscular exercises and gait retraining to prevent the development of OA after an injury occurs. A review of the current literature shows that no studies have been performed to evaluate methods of neuromuscular prehabilitation to prevent PTOA after a joint injury. Instead, current research has focused on management strategies after knee injuries, the value of exercise in the management of OA, and neuromuscular exercises after total knee arthroplasty. Recent work in gait retraining that alters knee joint loading holds promise for preventing the development of PTOA after joint trauma. Future research should evaluate methods of neuromuscular prehabilitation strategies in relationship to the outcome of PTOA after joint injury.


Congenital Dermal Sinus and Limited Dorsal Myeloschisis: "Spectrum Disorders" of Incomplete Dysjuction Between Cutaneous and Neural Ectoderms.
The existence of tethering tracts in spinal dysraphism, other than congenital dermal sinus (CDS), has been recognized and has been summated into an integrated concept of limited dorsal myeloschisis (LDM). To elucidate the underlying embryology of LDM in relation to CDS by focusing on the pathological features of special cases of tethering tracts. Out of 389 spinal dysraphism patients who were operated on from 2010 to 2016, 5 patients who had tethering tracts composed of both CDS and LDM (or "probable LDM" if only fibrous tissue was found) were identified. Their clinical presentation, radiological images, operative findings, and pathology were thoroughly reviewed. Three nonsaccular-type patients harbored stalks in which the squamous epithelial lined sinus (CDS) was found in the distal portion, and fibroneural (LDM) or fibrous (probable LDM) tissue in the proximal part. Two patients had saccular lesions, and a stalk was found inside the sac, connecting a small pit on the skin to the spinal cord. The tracts were pathologically identical to a CDS. This study reports the coexistence of CDS and LDM (or probable LDM) components. These unique cases support the hypothesis that the CDS and LDM are among a spectrum of an anomaly that is caused by failure of complete dysjunction between cutaneous and neural ectoderms. Neurosurgeons should be aware of the possibility of coexisting "CDS" components in cases suggestive of LDM. In such cases, not only untethering but also meticulous removal of the squamous epithelium is critical.


Are knee and foot orthopedic problems more disabling in the superobese?
Aiming to ascertain whether frequency and severity of knee and foot problems were different between morbid obesity (MO) and superobesity (SO), a prospective clinical study was designed. Bariatric candidates (N = 81, body mass index 40-81.3 kg/m(2), 43.2 % with SO) were submitted to knee and foot radiologic assessment, baropodometric footprint measurement, and the questionnaires Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Foot and Ankle Outcome Score (FAOS). Main outcome measures were imaging diagnosis of knee osteoarthritis and flatfoot, along with functional impact on activities of daily living estimated by the questionnaires. Knee osteoarthritis was radiologically diagnosed in 74.1 % (60/81), and the entire cohort suffered from flatfoot according to both footprint index and talar-first metatarsal radiographic angle; nevertheless, distribution was not different between SO and MO. However, WOMAC and FAOS scores were markedly worse in SO, affecting joint pain, stiffness, and general mobility. This is the first protocol of our knowledge to address foot and knee derangements in SO. Functional impairment was more severe in SO, despite a morphologic pattern similar to MO. Even though amelioration is probable with weight loss, long-term orthopedic assistance might be required in such circumstances.


Vaginal and bladder angiosarcoma after therapeutic irradiation.
Angiosarcoma involving the female genitourinary tract is a rare soft tissue malignancy of vascular origin. We have described probably the first reported case of postirradiation angiosarcoma involving the vagina and bladder, and have reviewed the existing literature on the subject of angiosarcoma resulting from previous therapeutic irradiation for gynecologic malignancy.


The Microbial Nitrogen Cycling, Bacterial Community Composition, and Functional Potential in a Natural Grassland Are Stable from Breaking Dormancy to Being Dormant Again.
The quantity of grass-root exudates varies by season, suggesting temporal shifts in soil microbial community composition and activity across a growing season. We hypothesized that bacterial community and nitrogen cycle-associated prokaryotic gene expressions shift across three phases of the growing season. To test this hypothesis, we quantified gene and transcript copy number of nitrogen fixation (nifH), ammonia oxidation (amoA, hao, nxrB), denitrification (narG, napA, nirK, nirS, norB, nosZ), dissimilatory nitrate reduction to ammonia (nrfA), and anaerobic ammonium oxidation (hzs, hdh) using the pre-optimized Nitrogen Cycle Evaluation (NiCE) chip. Bacterial community composition was characterized using V3-V4 of the 16S rRNA gene, and PICRUSt2 was used to draw out functional inferences. Surprisingly, the nitrogen cycle genes and transcript quantities were largely stable and unresponsive to seasonal changes. We found that genes and transcripts related to ammonia oxidation and denitrification were different for only one or two time points across the seasons (p < 0.05). However, overall, the nitrogen cycling genes did not show drastic variations. Similarly, the bacterial community also did not vary across the seasons. In contrast, the predicted functional potential was slightly low for May and remained constant for other months. Moreover, soil chemical properties showed a seasonal pattern only for nitrate and ammonium concentrations, while ammonia oxidation and denitrification transcripts were strongly correlated with each other. Hence, the results refuted our assumptions, showing stability in N cycling and bacterial community across growing seasons in a natural grassland.


Electronic anisotropy between open shell atoms in first and second order perturbation theory.
The interaction between two atoms in states with nonzero electronic orbital angular momenta is anisotropic and can be represented by a spherical tensor expansion. The authors derive expressions for the first order (electrostatic) and second order (dispersion and induction) anisotropic interaction coefficients in terms of the multipole moments and dynamic polarizabilities of the atoms and show that a complete description of the second order interaction requires odd rank or "out-of-phase" polarizabilities. The authors relate the tensorial expansion coefficients to the adiabatic Born-Oppenheimer potentials of the molecule and show that there are linear, and in some cases nonlinear, constraints on the van der Waals coefficients of these potentials.


Heterometallic Benzenehexathiolato Coordination Nanosheets: Periodic Structure Improves Crystallinity and Electrical Conductivity.
Coordination nanosheets are an emerging class of 2D, bottom-up materials having fully π-conjugated, planar, graphite-like structures with high electrical conductivities. Since their discovery, great effort has been devoted to expand the variety of coordination nanosheets; however, in most cases, their low crystallinity in thick films hampers practical device applications. In this study, mixtures of nickel and copper ions are employed to fabricate benzenehexathiolato (BHT)-based coordination nanosheet films, and serendipitously, it is found that this heterometallicity preferentially forms a structural phase with improved film crystallinity. Spectroscopic and scattering measurements provide evidence for a bilayer structure with in-plane periodic arrangement of copper and nickel ions with the NiCu2 BHT formula. Compared with homometallic films, heterometallic films exhibit more crystalline microstructures with larger and more oriented grains, achieving higher electrical conductivities reaching metallic behaviors. Low dependency of Seebeck coefficient on the mixing ratio of nickel and copper ions supports that the large variation in the conductivity data is not caused by change in the intrinsic properties of the films. The findings open new pathways to improve crystallinity and to tune functional properties of 2D coordination nanosheets.


Safety and efficacy of high-dose daptomycin as salvage therapy for severe gram-positive bacterial sepsis in hospitalized adult patients.
Increasing the dosage of daptomycin may be advantageous in severe infection by enhancing bactericidal activity and pharmacodynamics. However, clinical data on using daptomycin at doses above 6 mg/kg in Asian population are limited. A retrospective observational cohort study of all hospitalized adult patients treated with daptomycin (> 6 mg/kg) for at least 72 hours was performed in Taiwan. A total of 67 patients (40 males) with a median age of 57 years received a median dose of 7.61 mg/kg (range, 6.03-11.53 mg/kg) of daptomycin for a median duration of 14 days (range, 3-53 days). Forty-one patients (61.2%) were in intensive care units (ICU). Sites of infections included complicated skin and soft tissue infections (n = 16), catheter-related bacteremia (n = 16), endocarditis (n = 11), primary bacteremia (n = 10), osteomyelitis and septic arthritis (n = 9), and miscellaneous (n = 5). The median Pitt bacteremia score among the 54 (80.6%) patients with bacteremia was 4. The most common pathogen was methicillin-resistant Staphylococcus aureus (n = 38). Fifty-nine patients (88.1%) were treated with daptomycin after glycopepetide use. Overall, 52 (77.6%) patients achieved clinical success. The all-cause mortality rate at 28 day was 35.8%. In multivariate analysis, the significant predictors of in-hospital mortality in 54 bacteremic patients were malignancies (P = 0.01) and ICU stay (P = 0.02). Adverse effects of daptomycin were generally well-tolerated, leading to discontinuation in 3 patients. Daptomycin-related creatine phosphokinase (CPK) elevations were observed in 4 patients, and all received doses > 8 mg/kg. Treatment with high dose daptomycin as salvage therapy was generally effective and safe in Taiwan. CPK level elevations were more frequent in patients with dose > 8 mg/kg.


The relationship between quality of life and self-determination: an international study.
The aim of this study was to evaluate the relationship between self-determination and quality of life (QOL) of persons with intellectual disabilities (ID) living in four countries (Canada, United States, Belgium and France). Participants were 182 adults with mild ID living in community settings (with families, living independently or in supported living environments). QOL was measured with the Quality of Life Questionnaire. Self-determination was measured using the Adult version of The Arc's Self-Determination Scale. Discriminant function and correlational analyses were conducted. Discriminant function analysis indicated that essential characteristics of self-determination predicted membership in the high QOL group and that overall self-determination and QOL were significantly correlated, as were sub-scale scores. The study replicates findings from a previous study with an international sample and confirms the importance of self-determination to enhance QOL. Subsequent research should examine the direction of the relationship between self-determination and QOL and examine the relationship of essential characteristics of self-determined behaviour and core domains of QOL in greater detail.


Hypokalaemia in the elderly: is it always diuretic-induced?
Serum potassium was measured within 24 hours in 156 patients (48 male, 108 female) with an average age of 81.9 years admitted to the unit with acute illness. Of the 156 patients, 88 (56.4%) were taking diuretics (none was on ACE inhibitors); 20 patients (12.8%) were also on digoxin therapy. In all, 24 patients (16%) had hypokalaemia and 3 (2%) hyperkalaemia. Hypokalaemia was seen in patients associated with acute illness. There was no significant difference between the diuretic and non-diuretic groups. Monitoring of serum potassium is not routinely indicated to detect hypokalaemia in patients on diuretic therapy except in those with severe hepatic or renal impairment or those on digoxin.


[Perspectives on the amyloid cascade hypothesis of Alzheimer's disease].
The amyloid-beta peptide cascade hypothesis has provided a useful framework for the research on Alzheimer's disease for nearly 20 years. According to this hypothesis, an increase in amyloid-beta levels triggers all of the pathological features of the disease, including tau hyperphosphorylation, appearance of neurofibrillary tangles, synaptic dysfunction and neuronal cell death. Even though amyloid-beta peptide has an important role in the neurodegenerative process, different findings, such as the presence of abundant plaques in old cognitively normal individuals or the limited success of therapeutical approaches targeting only amyloid-beta, cast some doubt on a unique role for this peptide. At present, it is rather accepted that amyloid-beta peptide acts in parallel with other factors causing Alzheimer's disease that should be also considered at the time of designing useful therapeutic strategies.


Inhibition characteristics of biofilm structure of Staphylococcus aureus.
Different extracts have different effects on the biofilm structure of Staphylococcus aureus, and the biofilm structure of Staphylococcus aureus will produce different inhibition reactions. In this study, different experimental reagent extracts were used to analyze the inhibition characteristics of Staphylococcus aureus biofilm structure. The inhibition characteristics of bacterial biofilm structure were obtained by using the same bacteria species and the same experimental environment. The results showed that the chloroform extract had a good inhibitory effect on the biofilm structure, which could effectively inhibit the formation of biofilm; the acetic acid extract had an impact on the formation of biofilm, which was destructive to the biofilm; the petroleum ether extract had no effect on the formation of biofilm, that is, it had no inhibitory effect.


[Study on the Role and Mechanism of METTL3 Mediating the Up-regulation of m6A Modified Long Non-coding RNA THAP7-AS1 in Promoting the Occurrence of Lung Cancer].
Lung cancer is a major threat to human health. The molecular mechanisms related to the occurrence and development of lung cancer are complex and poorly known. Exploring molecular markers related to the development of lung cancer is helpful to improve the effect of early diagnosis and treatment. Long non-coding RNA (lncRNA) THAP7-AS1 is known to be highly expressed in gastric cancer, but has been less studied in other cancers. The aim of the study is to explore the role and mechanism of methyltransferase-like 3 (METTL3) mediated up-regulation of N6-methyladenosine (m6A) modified lncRNA THAP7-AS1 expression in promoting the development of lung cancer. Samples of 120 lung cancer and corresponding paracancerous tissues were collected. LncRNA microarrays were used to analyze differentially expressed lncRNAs. THAP7-AS1 levels were detected in lung cancer, adjacent normal tissues and lung cancer cell lines by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The diagnostic value of THAP7-AS1 in lung cancer and the relationship between THAP7-AS1 expression and survival rate and clinicopathological parameters were analyzed. Bioinformatics analysis, methylated RNA immunoprecipitation (meRIP), RNA pull-down and RNA-immunoprecipitation (RIP) assay were used to investigate the molecular regulation mechanism of THAP7-AS1. Cell proliferation, migration, invasion and tumorigenesis of SPC-A-1 and NCI-H1299 cells were determined by MTS, colony-formation, scratch, Transwell and xenotransplantation in vivo, respectively. Expression levels of phosphoinositide 3-kinase/protein kenase B (PI3K/AKT) signal pathway related protein were detected by Western blot. Expression levels of THAP7-AS1 were higher in lung cancer tissues and cell lines (P<0.05). THAP7-AS1 has certain diagnostic value in lung cancer [area under the curve (AUC)=0.737], and its expression associated with overall survival rate, tumor size, tumor-node-metastasis (TNM) stage and lymph node metastasis (P<0.05). METTL3-mediated m6A modification enhanced THAP7-AS1 expression. The cell proliferation, migration, invasion and the volume and mass of transplanted tumor were all higher in the THAP7-AS1 group compared with the NC group and sh-NC group of SPC-A-1 and NCI-H1299 cells, while the cell proliferation, migration and invasion were lower in the sh-THAP7-AS1 group (P<0.05). THAP7-AS1 binds specifically to Cullin 4B (CUL4B). The cell proliferation, migration, invasion, and expression levels of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), phosphoinositide-3 kinase, catalytic subunit delta (PIK3CD), phospho-phosphatidylinositol 3-kinase (p-PI3K), phospho-protein kinase B (p-AKT) and phospho-mammalian target of rapamycin (p-mTOR) were higher in the THAP7-AS1 group compared with the Vector group of SPC-A-1 and NCI-H1299 cells (P<0.05). LncRNA THAP7-AS1 is stably expressed through m6A modification mediated by METTL3, and combines with CUL4B to activate PI3K/AKT signal pathway, which promotes the occurrence and development of lung cancer.


The Paradox of Interactive Media: The Potential for Video Games and Virtual Reality as Tools for Violence Prevention.
Interactive media such as video games and virtual reality (VR) provide users with lived experiences that may be dangerous or even impossible in daily life. By providing interactive experiences in highly authentic, detail-rich contexts, these technologies have demonstrated measurable success in impacting how people think, feel, and behave in the physical world. At the same time, violent interactive media content has been historically connected with a range of antisocial effects in both popular press and academic research. Extant literature has established a small-but-statistically significant effect of interactive media violence on aggressive thoughts and behaviors, which could serve as a risk factor for interpersonal violence. However, left unexplored is the seemingly paradoxical claim that under some conditions, interactive media experiences might protect against interpersonal violence. Drawing on advances in media theory and research and the evolution of interactive media content and production practices, the current manuscript suggests ways in which interactive media violence may be leveraged to lower the likelihood of real-world violence experiences. For example, research on both violent and non-violent games has found that players can (a) express guilt after committing violent acts, (b) report reflective and introspective emotional reactions during gameplay, and (c) debate the morality of their actions with others. Regarding VR, studies have demonstrated that (a) witnessing physical violence in immersive spaces led participants to take the perspective of victims and better understand their emotional state and (b) controlled exposure to traumatic or violent events can be used for treatment. Broadly, studies into video games and VR demonstrate that the impact of actions in virtual worlds transfer into the physical worlds to influence (later) attitudes and behaviors. Thus, how these experiences may be potentially harnessed for social change is a compelling and open consideration, as are side-effects of such interventions on vulnerable groups. The current manuscript summarizes emerging research perspectives (as well as their limitations) to offer insight into the potential for interactive media violence to protect against real-world violence victimization and perpetration.


Effects of standard surgical procedures on the patellar blood flow in monkeys.
The effects of various surgical dissections on the patellar blood flow were studied in ten monkeys by the use of the hydrogen washout technique. The patellar blood flow was decreased to an average of 65% of the control value after an extensive medial parapatellar arthrotomy. When the infrapatellar fat pad was completely removed following extensive medial arthrotomy, the blood flow further decreased to an average of 49% of the control. When a lateral retinacular release with sacrifice of the lateral superior genicular artery was performed following the medial arthrotomy, the blood flow decreased to an average of 53% of the control. When a lateral release was combined with removal of the fat pad following the main medial arthrotomy, the patellar blood flow showed marked decrease to an average of only 17% of the control. The vascular anatomic study demonstrated that many vessels penetrate from the fat pad into the inferior pole of the patella. It is suggested that the lateral superior genicular artery and/or the fat pad should be carefully preserved to avoid ischemia of the patella during extensive procedures such as total knee arthroplasty.


An acute increase of peritubular K stimulates K transport through cell pathways of CCT.
In this study, we have investigated net transport and electrical properties of isolated perfused cortical collecting ducts of control and DOCA-treated rabbits to clarify the cell mechanism for secreting K on an acute increase of peritubular K concentration. Raising bath K in control experiments caused an increase in net K secretion (-JK) and net Na absorption (JNa). Barium (5 mM), a known blocker of basolateral K conductance, added to the bath had no effect on this transport stimulation. In the presence of luminal Ba (5 mM) -JK was reduced to zero, but JNa was unaltered. When bath K was increased -JK increased to a value slightly greater than zero, but not different from the predicted passive flux through the paracellular pathway. In tubules of DOCA-treated rabbits, raising K in the bath increased -JK and JNa. The observed stimulation of -JK was blunted in the presence of Ba in the bath, whereas the increase in JNa remained the same. Thus, in DOCA-treated tubules, Ba in the bath significantly attenuated the increase in K secretion without affecting the transport stimulation of JNa. When Ba was added to the perfusate and bath K increased, -JK, which was initially 22.1, increased to 36.4 pmol.mm-1.min-1. Thus a "Ba-insensitive" pathway became more evident in CCTs from DOCA-treated rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)


Hodgkin lymphoma incidence in ethnic enclaves in California.
Hodgkin lymphoma (HL) incidence varies with migration and nativity, suggesting an influence of acculturation on risk. In population-based California data including 1483 Hispanic and 348 Asian/Pacific Islander (API) HL cases, we examined HL rates in residential neighborhoods classified by ethnic enclave status (measuring degree of acculturation) and socioeconomic status (SES). Rates were inversely associated with enclave intensity, although associations varied by gender and race. In females, the enclave effect was stronger in low-SES settings, but rates were higher in less-ethnic/high-SES than more-ethnic/low-SES neighborhoods--diminishing enclave intensity affected rates more than higher SES. In Hispanics, associations were modest, and only females experienced SES modification of rates; in APIs, the enclave effect was much stronger. Thus, acculturation measured by residence in ethnic enclaves affects HL rates independently of neighborhood SES but in complex patterns. Living in less-ethnic neighborhoods may increase HL rates by facilitating social isolation and other gender-specific exposures implicated in risk.


Hemoglobinopathy control program in Turkey.
Hemoglobinopathies are a very important health problem in Turkey. To date many studies have been performed but there has been no national hemoglobinopathy control program (HCP). After the Turkish National Hemoglobinopathy Council (TNHC) was created all centers, foundations, and associations were combined into one organization controlled by the Ministry of Health (MOH). The MOH and the TNHC have started to register the results of the screening of 377,339 healthy subjects from 16 different cities and the recorded average frequency of the beta-thalassemia trait was 4.3%. The highest prevalence of thebeta-thalassemia trait (13.1%) was found in the Antalya region and of the HbS trait (10%) in the Cukurova region. Next, written regulations for the Fight against Hereditary Blood Disease were published especially for preventing and treating hemoglobinopathies. The MOH and the TNHC selected 33 provinces situated in the Thrace, Marmara, Aegean, Mediterranean and South Eastern regions with a high birth prevalence of severe hemoglobinopathies. The hemoglobinopathy scientific committee was set up, a guidebook was published and a national HCP was started in these high-risk provinces.


Analysis of angiogenesis biomarkers for ramucirumab efficacy in patients with metastatic colorectal cancer from RAISE, a global, randomized, double-blind, phase III study.
The phase III RAISE trial (NCT01183780) demonstrated that the vascular endothelial growth factor (VEGF) receptor (VEGFR)-2 binding monoclonal antibody ramucirumab plus 5-fluororuracil, leucovorin, and irinotecan (FOLFIRI) significantly improved overall survival (OS) and progression-free survival (PFS) compared with placebo + FOLFIRI as second-line metastatic colorectal cancer (mCRC) treatment. To identify patients who benefit the most from VEGFR-2 blockade, the RAISE trial design included a prospective and comprehensive biomarker program that assessed the association of biomarkers with ramucirumab efficacy outcomes. Plasma and tumor tissue collection was mandatory. Overall, 1072 patients were randomized 1 : 1 to the addition of ramucirumab or placebo to FOLFIRI chemotherapy. Patients were then randomized 1 : 2, for the biomarker program, to marker exploratory (ME) and marker confirmatory (MC) groups. Analyses were carried out using exploratory assays to assess the correlations of baseline marker levels [VEGF-C, VEGF-D, sVEGFR-1, sVEGFR-2, sVEGFR-3 (plasma), and VEGFR-2 (tumor tissue)] with clinical outcomes. Cox regression analyses were carried out for each candidate biomarker with stratification factor adjustment. Biomarker results were available from >80% (n = 894) of patients. Analysis of the ME subset determined a VEGF-D level of 115 pg/ml was appropriate for high/low subgroup analyses. Evaluation of the combined ME + MC populations found that the median OS in the ramucirumab + FOLFIRI arm compared with placebo + FOLFIRI showed an improvement of 2.4 months in the high VEGF-D subgroup [13.9 months (95% CI 12.5-15.6) versus 11.5 months (95% CI 10.1-12.4), respectively], and a decrease of 0.5 month in the low VEGF-D subgroup [12.6 months (95% CI 10.7-14.0) versus 13.1 months (95% CI 11.8-17.0), respectively]. PFS results were consistent with OS. No trends were evident with the other antiangiogenic candidate biomarkers. The RAISE biomarker program identified VEGF-D as a potential predictive biomarker for ramucirumab efficacy in second-line mCRC. Development of an assay appropriate for testing in clinical practice is currently ongoing. NCT01183780.


[Diffuse poliencephalitis and visceral neoplasm (author's transl)].
A case of diffuse polioencephalitis associated with non-differentiated bronchial carcinoma is reported. Clinically the patient presented mental distrubance and an extra-pyramidal syndrome. Anatomopathological investigation revealed inflammation of the cerebral hemispheres and the brain stem. Similar involvement of others regions of the central nervous system has been reported in the literature, probably indicating various locations of a single nosological entity. A viral origin is probable but not yet established.


Premating isolation is determined by larval rearing substrates in cactophilic Drosophila mojavensis. X. Age-specific dynamics of adult epicuticular hydrocarbon expression in response to different host plants.
Analysis of sexual selection and sexual isolation in Drosophila mojavensis and its relatives has revealed a pervasive role of rearing substrates on adult courtship behavior when flies were reared on fermenting cactus in preadult stages. Here, we assessed expression of contact pheromones comprised of epicuticular hydrocarbons (CHCs) from eclosion to 28 days of age in adults from two populations reared on fermenting tissues of two host cacti over the entire life cycle. Flies were never exposed to laboratory food and showed significant reductions in average CHC amounts consistent with CHCs of wild-caught flies. Overall, total hydrocarbon amounts increased from eclosion to 14-18 days, well past age at sexual maturity, and then declined in older flies. Most flies did not survive past 4 weeks. Baja California and mainland populations showed significantly different age-specific CHC profiles where Baja adults showed far less age-specific changes in CHC expression. Adults from populations reared on the host cactus typically used in nature expressed more CHCs than on the alternate host. MANCOVA with age as the covariate for the first six CHC principal components showed extensive differences in CHC composition due to age, population, cactus, sex, and age × population, age × sex, and age × cactus interactions. Thus, understanding variation in CHC composition as adult D. mojavensis age requires information about population and host plant differences, with potential influences on patterns of mate choice, sexual selection, and sexual isolation, and ultimately how these pheromones are expressed in natural populations. Studies of drosophilid aging in the wild are badly needed.


Perioperative glycaemic control for diabetic patients undergoing surgery.
Patients with diabetes mellitus are at increased risk of postoperative complications. Data from randomised clinical trials and meta-analyses point to a potential benefit of intensive glycaemic control, targeting near-normal blood glucose, in patients with hyperglycaemia (with and without diabetes mellitus) being submitted to surgical procedures. However, there is limited evidence concerning this question in patients with diabetes mellitus undergoing surgery. To assess the effects of perioperative glycaemic control for diabetic patients undergoing surgery. Trials were obtained from searches of The Cochrane Library, MEDLINE, EMBASE, LILACS, CINAHL and ISIS (all up to February 2012). We included randomised controlled clinical trials that prespecified different targets of perioperative glycaemic control (intensive versus conventional or standard care) Two authors independently extracted data and assessed risk of bias. We summarised studies using meta-analysis or descriptive methods. Twelve trials randomised 694 diabetic participants to intensive control and 709 diabetic participants to conventional glycaemic control. The duration of the intervention ranged from just the duration of the surgical procedure up to 90 days. The number of participants ranged from 13 to 421, and the mean age was 64 years. Comparison of intensive with conventional glycaemic control demonstrated the following results for our predefined primary outcomes: analysis restricted to studies with low or unclear detection or attrition bias for infectious complications showed a risk ratio (RR) of 0.46 (95% confidence interval (CI) 0.18 to 1.18), P = 0.11, 627 participants, eight trials, moderate quality of the evidence (grading of recommendations assessment, development and evaluation - (GRADE)). Evaluation of death from any cause revealed a RR of 1.19 (95% CI 0.89 to 1.59), P = 0.24, 1365 participants, 11 trials, high quality of the evidence (GRADE).On the basis of a posthoc analysis, there is the hypothesis that intensive glycaemic control may increase the risk of hypoglycaemic episodes if longer-term outcome measures are analysed (RR 6.92, 95% CI 2.04 to 23.41), P = 0.002, 724 patients, three trials, low quality of the evidence (GRADE). Analysis of our predefined secondary outcomes revealed the following findings: cardiovascular events had a RR of 1.03 (95% CI 0.21 to 5.13), P = 0.97, 682 participants, six trials, moderate quality of the evidence (GRADE) when comparing the two treatment modalities; and renal failure also did not show significant differences between intensive and regular glucose control (RR 0.61, 95% CI 0.34 to 1.08), P = 0.09, 434 participants, two trials, moderate quality of the evidence (GRADE). We did not meta-analyse length of hospital stay and intensive care unit (ICU) stay due to substantial unexplained heterogeneity. Mean differences between intensive and regular glucose control groups ranged from -1.7 days to 2.1 days for ICU stay and between -8 days to 3.7 days for hospital stay (moderate quality of the evidence (GRADE)). One trial assessed health-related quality of life in 12/37 (32.4%) of participants in the intervention group and 13/44 (29.5%) of participants in the control group, and did not show an important difference (low quality of the evidence (GRADE)) in the measured physical health composite score of the short-form 12-item health survey (SF-12). None of the trials examined the effects of the interventions in terms of costs. The included trials did not demonstrate significant differences for most of the outcomes when targeting intensive perioperative glycaemic control compared with conventional glycaemic control in patients with diabetes mellitus. However, posthoc analysis indicated that intensive glycaemic control was associated with an increased number of patients experiencing hypoglycaemic episodes. Intensive glycaemic control protocols with near-normal blood glucose targets for patients with diabetes mellitus undergoing surgical procedures are currently not supported by an adequate scientific basis. We suggest that insulin treatment regimens, patient- and health-system relevant outcomes, and time points for outcome measures should be defined in a thorough and uniform way in future studies.


Pathobiology of focal segmental glomerulosclerosis: new developments.
Focal segmental glomerulosclerosis (FSGS) is a major cause of nephrotic syndrome and renal failure. All forms of FSGS share podocyte injury and depletion as central mediators. This review focuses on new insights into pathogenesis from study of extrinsic toxins in experimental models, permeability factors in human disease, and novel genetic causes. Experimental toxin models have advanced our understanding of the threshold and dynamics of podocyte injury. Following initial podocyte depletion, spreading fields of podocyte injury through secondary mediators appear to be important in generating the segmental pathologic lesions. Proliferating glomerular epithelial cells are common in FSGS, although there are conflicting views about their identity. Evidence suggests potential contributions by mature parietal epithelial cells, facultative stem cells and podocytes. A number of novel candidate permeability factors that affect podocyte function and motility have been discovered in human FSGS and related podocytopathy minimal change disease. Exome capture has identified new monogenic causes of familial FSGS. Apolipoprotein L-1 (APOL1) is expressed in podocytes, and the prevalence of APOL1 risk alleles in patients of African descent with primary FSGS and HIV-associated nephropathy is high, implicating potential podocyte effects. FSGS is caused by a complex interplay of inherent genetic susceptibilities and external injurious factors acting on podocytes. Critical levels of podocyte stress eventuate in podocyte depletion, segmental glomerular scarring, and glomerular epithelial cell hyperplasia.


Simian virus 40 DNA replication in nuclear monolayers.
Simian virus 40 DNA replication has been studied in nuclear monolayers prepared by treatment of monolayers of BSC-1 monkey kidney cells with Nonidet P-40. These nuclear monolayers incorporated [3H]TTP into two types of viral replicative intermediates that sediment as 25-26S and 22-23S species, respectively, in neutral sucrose gradients. The 22-23S species behaves, in dye buoyant density equilibrium gradients, as a late replicative intermediate. Examination of both species in alkaline sucrose gradients revealed the presence of two types of newly synthesized strands: (i) 4-7S strands and (ii) full-length, or nearly full-length, 10-16S strands. At low TTP concentrations (less than 0.5 muM), the two size classes were found in approximately equal amounts. However, at 10 to 50 muM TTP, the proportion of the longer strands increased, with a corresponding decrease in the relative amount of the 4-7S species. Thus, the joining of small, Okazaki-like fragments to the growing chain appears to require a much higher concentration of TTP than the synthesis of the fragments themselves. Replicating simian virus 40 DNA synthesized in the nuclear monolayers is is associated with "M bands", as previously demonstrated for replicating simian virus 40 DNA in cultured whole cells.


Policy Agenda-Setting and Causal Stories: Examining How Organized Interests Redefined the Problem of Refugee Health Policy in Canada.
The development of refugee health policies is significant, given the increased volume of displaced persons seeking refuge in Canada and around the world. Changes to the Canadian refugee health policy, known as the Interim Federal Health Program (IFHP), limited healthcare access for refugees and refugee claimants from 2012 to 2016. In this article, we present a policy analysis using the case of the IFHP retrenchments to examine how political actors on opposing sides of the issue defined the problem using different causal story mechanisms. This analysis reveals that organized interests dramatically changed the problem definition of the IFHP reforms. Following their use of causal stories in redefining the problem, the courts declared that the reforms to refugee healthcare were a form of cruel and unusual treatment. Understanding policy strategies used by proponents of refugee healthcare coverage expansion is important for countries responding to the current, enduring refugee crisis.


["Do this, do that, but I'm falling down..."--understanding Crohn's disease].
This qualitative study was developed as an effort to understand the meaning and the impact of Chron's Disease on the carrier's life, opting for Life Oral History as the methodological reference and having as a base Hippocrates' monist philosophical school, for which the medical practice focuses on the sick person in his/her totality, taking into consideration his/her temperament and background. The therapeutics must reestablish the person's harmony with his/her environment and with himself/ herself. It is an integrative, dynamic medicine that corresponds to the beginnings of psychosomatic medicine. The studies on Chron's Disease, through psychosomatic understanding, made possible to analyze the symptoms not as alien bodies to be eradicated, but as messengers of an appeal to be understood. Through them, the person's history can be recovered, which makes possible the development to more advanced levels of understanding if it is experienced and analyzed consciously.


Mechanisms and consequences of endothelial nitric oxide synthase dysfunction in hypertension.
Reduced nitric oxide bioavailability contributes to endothelial dysfunction and hypertension. The endothelial isoform of nitric oxide synthase (eNOS) is responsible for the production of nitric oxide within the endothelium. Loss of eNOS cofactor tetrahydrobiopterin to initial increase in oxidative stress leads to uncoupling of eNOS, in which the enzyme produces superoxide anion rather than nitric oxide, further substantiating oxidative stress to induce vascular pathogenesis. The current review focuses on recent advances on the molecular mechanisms and consequences of eNOS dysfunction in hypertension, and potential novel therapeutic strategies restoring eNOS function to treat hypertension.


Dentine collagen cross-linking using tiopronin-protected Au/EDC nanoparticles formulations.
The aim of this study was to investigate EDC-assisted collagen crosslinking effect with different concentrations of tiopronin-protected gold (TPAu) nanoparticles on demineralized dentine. TPAu nanoparticles were fabricated from 0.31-g tetrachloroauric acid and 0.38-g of N-(2-mercaptopropionyl) glycine (2.4-mmol). Then co-dissolved using 35-mL of 6:1 methanol/acetic acid and mixed using NaBH4. EDC (0.3-M) was conjugated to TPAu nanoparticles at TPAU/EDC-0.25:1, and TPAU/EDC-0.5:1 treatment formulations ratios. Dentin specimens treated with 0.3-M EDC solution alone or left untreated were used as control. Nanoparticles formulations were characterized in term of particles morphology and size, Zeta potential, thermogravimetric analysis and small-angle X-ray scattering. Dentin substrates were characterized in term of TEM investigation, dentin proteases characterization, hydroxyproline liberation, elastic modulus measurement, Raman analysis and confocal microscopy viewing. TEM evaluation of tiopronin protected gold nanoparticles dispersion revealed nano-clusters formations in both groups. However, based on our TEM measurements, the particle-size was ranging from ˜20 to 50 nm with spherical core-shape which were almost similar for both TPAu/EDC ratios (0.5:1 and 0.25:1). Zeta potential measurements indicate negative nanoparticles surface charge. SAXS profiles for both formulations, suggest a typical profile for uni-lamellar nanoparticles. Superior dentin collagen cross-linking effect was found with the TPAu/EDC nanoparticles formulations compared to the control and EDC treated groups. Cross-linking of dentin collagen using TPAu coupled with EDC through TPAu/EDC nanoparticles formulations is of potential significance in improving the biodegradation resistance, proteases inhibition, mechanical and structural stability of demineralized dentin substrates. In addition, the cross-linking effect is dependent on TPAu/EDC ratio, whereas higher cross-linking effect was found at TPAu/EDC ratio of 0.5:1.


Synthesis, molecular structure, computational study and in vitro anticancer activity of dinuclear thiolato-bridged pentamethylcyclopentadienyl Rh(III) and Ir(III) complexes.
Neutral dinuclear dithiolato-bridged pentamethylcyclopentadienyl Rh(III) complexes of the type (C5Me5)2Rh2(μ-SR)2Cl2 (R = CH2Ph, 1; R = CH2CH2Ph, 2) and cationic dinuclear trithiolato-bridged pentamethylcyclopentadienyl Rh(III) and Ir(III) complexes of the type [(C5Me5)2M2(μ-SR)3](+) (M = Rh, R = CH2Ph, 3; M = Rh, R = CH2CH2Ph, 5; M = Rh, R = CH2C6H4-p-(t)Bu, 7: M = Ir, R = CH2Ph, 4; M = Ir, R = CH2CH2Ph, 6; M = Ir, R = CH2C6H4-p-(t)Bu, 8) have been synthesized from the chloro-bridged pentamethylcyclopentadienyl Rh(III) and Ir(III) dimers (C5Me5)2M2(μ-Cl)2Cl2 by reaction with the corresponding thiol derivative (RSH). Complexes 3-8 were isolated as chloride salts. All complexes were obtained in good yield and were fully characterized by spectroscopic methods. The molecular structures of the neutral complexes (1 and 2) show interesting features: the two rhodium atoms are bridged by two thiolato ligands with no metal-metal bonds and the pentamethylcyclopentadienyl and chlorido ligands are oriented syn to each other, an uncommon conformation for such dinuclear complexes. These structural features were rationalized using DFT calculations. Additionally, the antiproliferative activity of the complexes was evaluated against the cancerous A2780 (cisplatin sensitive) and A2780cisR (cisplatin resistant) human ovarian cell lines and on the noncancerous HEK293 human embryonic kidney cells. All complexes were found to be active and the cationic iridium complexes , and are particularly cytotoxic, with IC50 values in the nanomolar range (IC50 < 0.1 μM). The catalytic activity of the complexes for the oxidation of glutathione (GSH) to GSSG was evaluated by NMR spectroscopy.


Evaluation of a low-cost, low-power syringe pump to deliver magnesium sulfate intravenously to pre-eclamptic women in a Malawian referral hospital.
Magnesium sulfate is an affordable and effective treatment for pre-eclampsia and eclampsia. In settings where infusion pumps are not available to regulate the flow rate of intravenous delivery, healthcare providers must administer magnesium sulfate (MgSO4) via time-consuming and painful, large-volume intramuscular injections. As an alternative to costly commercially available syringe pumps, we developed AutoSyp, an accurate, low-cost, and low-powered syringe pump designed to meet the needs and constraints these low-resource settings. This paper describes results of a pilot study to evaluate the feasibility of using AutoSyp to administer MgSO4 intravenously to women suffering from pre-eclampsia at a referral hospital in Blantyre, Malawi. AutoSyp was programmed to deliver MgSO4 following the Zuspan regimen to pregnant and post-partum women suffering from pre-eclampsia at Queen Elizabeth Central Hospital in Blatnyre, Malawi. Given the selection of either loading or maintenance dose on AutoSyp's user interface, the flow rate was automatically programmed to dispense 60 mL/h or 5 mL/h of 20% MgSO4 solution, respectively. During each treatment, the dispensed volume was automatically calculated by the device based on the plunger position and stored on a computer for accuracy analysis of the mean flow rate and total volume delivered. The clinical results for both the loading and maintenance dose administrations were compared to the device's accuracy during tests performed in the laboratory setting. Twenty-two women were enrolled in this study. In both the clinical and laboratory settings, the mean flow rate errors for the loading and maintenance dose infusions were under 2%. During 466 h of testing, the device sounded 129 occlusion alarms across 14 subjects. Of these, 71 alarms were false positives. Results of this study support the use of AutoSyp as a less painful and accurate means of MgSO4 administration in clinical environments that lack infusion systems. There were a large number of false alarms in the current system which will be addressed in future designs. AutoSyp maintains the comfort of intravenous MgSO4 administration, but unlike commercially available syringe pumps, it is capable of operating with a variety of syringe brands and sizes and requires no additional consumables. AutoSyp's appropriate design will benefit its implementation and sustained use in low-resource settings. Trial registered prospectively on November 18, 2014 with ClinicalTrials.gov ( NCT02296931 ).


Referred sensations in chronic pain patients.
This clinical note describes an unusual phenomenon of referred sensation reported in a sample of 98 chronic pain patients during electrical stimulation. Thirty-nine percent reported a variety of sensations referred to different parts of the body. Of these, 74% reported the sensations referred to the painful region. Among the sensations were paresthesias, pain, temperature changes, and pressure or constriction. The patients who had referred sensations had lower ratings of depression and had undergone more surgical operations than those who did not report referred sensations. Three case reports of patients with phantom limb pain are presented to illustrate the vividness with which these sensations are experienced. These data suggest that deafferentation due to disease, injury or other lesions of the CNS lead to a hypersensitivity and an increased likelihood of referred pain of long duration.


Antitumor and apoptosis-promoting properties of emodin, an anthraquinone derivative from Rheum officinale Baill, against pancreatic cancer in mice via inhibition of Akt activation.
Pancreatic adenocarcinoma is one of the most common malignancies worldwide. Gemcitabine is currently the standard first-line chemotherapeutic agent for pancreatic cancer. However, gemcitabine can induce activation of Akt and nuclear factor-κB (NF-κB), which is associated with its chemoresistance. It has been reported that gemcitabine combination therapies result in improved survival outcomes in pancreatic cancer. Therefore, agents that can either enhance the effects of gemcitabine or overcome chemoresistance to the drug are needed for the treatment of pancreatic cancer. Emodin is an active component of Chinese medicinal herbs and can inhibit the activation of Akt and NF-κB. In this study, we investigated whether emodin could enhance the anticancer effect of gemcitabine on pancreatic cancer in vivo. We demonstrated that treatment of gemcitabine combined with emodin efficiently suppressed tumor growth in mice inoculated with pancreatic tumor cells. This treatment paradigm promoted apoptotic cell death and mitochondrial fragmentation. Furthermore, it reduced phosphorylated-Akt (p-Akt) level, NF-κB activation and Bcl-2/Bax ratio, increased caspase-9 and -3 activation, Cytochrome C (CytC) release occurred in combination therapy. Collectively, emodin enhanced the activity of gemcitabine in tumor growth suppression via inhibition of Akt and NF-κB activation, thus promoting the mitochondrial-dependent apoptotic pathway. Therefore, our findings may provide new insights into understanding the pharmacological regulation of emodin on gemcitabine-mediated proapoptosis in pancreatic cancer and may aid in the design of new therapeutic strategies for the intervention of human pancreatic cancers.


Variation in elemental stoichiometry of the marine diatom Thalassiosira weissflogii (Bacillariophyceae) in response to combined nutrient stress and changes in carbonate chemistry.
The combined consequences of the multi-stressors of pH and nutrient availability upon the growth of a marine diatom were investigated. Thalassiosira weissflogii was grown in N- or P-limited batch culture in sealed systems, with pH commencing at 8.2 ("extant" conditions) or 7.6 ("ocean acidification" [OA] conditions), and then pH was allowed to either drift with growth, or was held fixed. Results indicated that within the pH range tested, the stability of environmental pH rather than its value (i.e., OA vs. extant) fundamentally influenced biomass accumul-ation and C:N:P stoichiometry. Despite large changes in total alkalinity in the fixed pH systems, final biomass production was consistently greater in these systems than that in drifting pH systems. In drift systems, pH increased to exceed pH 9.5, a level of alkalinity that was inhibitory to growth. No statis-tically significant differences between pH treatments were measured for N:C, P:C or N:P ratios during nutrient-replete growth, although the diatom expre-ssed greater plasticity in P:C and N:P ratios than in N:C during this growth phase. During nutrient-deplete conditions, the capacity for uncoupled carbon fixa-tion at fixed pH was considerably greater than that measured in drift pH systems, leading to strong contrasts in C:N:P stoichiometry between these treatments. Whether environmental pH was stable or drifted directly influenced the extent of physiological stress. In contrast, few distinctions could be drawn between "extant" versus "OA" conditions for cell physiology.


Physical activity, stress, and cardiovascular disease risk: HCHS/SOL Sociocultural Ancillary Study.
We assess whether the cross-sectional associations between moderate-vigorous physical activity (MVPA) and CVD risk factors are modified by various stress types. Complete baseline data from 4,000 participants, ages 18-74 years, of the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study (HCHS/SOL SCAS) were analyzed using complex survey design methods. Accelerometer-measured MVPA was assessed continuously (average minutes per day). CVD risk factors assessed were diabetes, hypercholesterolemia, hypertension, and obesity. Stress was assessed using the Chronic Burden Scale for chronic stress, Traumatic Stress Schedule for traumatic stress, and the Perceived Stress Scale for perceived stress. Poisson regression models estimated prevalence ratios of CVD risk factors. The interaction was evaluated by cross-product terms with p <0.10. There was a significant interaction between chronic stress and MVPA among those with prevalent diabetes (pinteraction = 0.09). Among those reporting low chronic stress, higher MVPA was associated with a low prevalence of diabetes, however among those reporting high chronic stress, the prevalence of diabetes remained high even with higher MVPA. We did not observe interactions between chronic stress and MVPA for the remaining CVD risk factors, or interactions between traumatic stress or perceived stress and MVPA. This study provides initial evidence on the role of chronic stress on the association between MVPA and diabetes for Hispanic/Latino adults. Mostly, however, chronic stress, traumatic stress, and perceived stress did not modify the associations between MVPA and CVD risk factors for Hispanic/Latino adults.


Diversity and spoilage potential of microbial communities associated with grape sour rot in eastern coastal areas of China.
As a polymicrobial disease, sour rot decreases grape berry yield and wine quality. The diversity of microbial communities in sour rot-affected grapes depends on the cultivation site, but the microbes responsible for this disease in eastern coastal China, has not been reported. To identify the microbes that cause sour grape rot in this important grape-producing region, the diversity and abundance of bacteria and fungi were assessed by metagenomic analysis and cultivation-dependent techniques. A total of 15 bacteria and 10 fungi were isolated from sour rot-affected grapes. High-throughput sequencing of PCR-amplicons generated from diseased grapes revealed 1343 OTUs of bacteria and 1038 OTUs of fungi. Proteobacteria and Firmicutes were dominant phyla among the 19 bacterial phyla identified. Ascomycota was the dominant fungal phylum and the fungi Issatchenkia terricola, Colletotrichum viniferum, Hanseniaspora vineae, Saprochaete gigas, and Candida diversa represented the vast majority ofmicrobial species associated with sour rot-affected grapes. An in vitro spoilage assay confirmed that four of the isolated bacteria strains (two Cronobacter species, Serratia marcescens and Lysinibacillus fusiformis) and five of the isolated fungi strains (three Aspergillus species, Alternaria tenuissima, and Fusarium proliferatum) spoiled grapes. These microorganisms, which appear responsible for spoiling grapes in eastern China, appear closely related to microbes that cause this plant disease around the world.


Femoral Osteomyelitis Caused by Cladophialophora in a Patient without Known Immunocompromise.
Chronic osteomyelitis associated with a stage IV decubitus ulcer is a challenging condition to manage, characterized by frequent relapses and need for long-term anti-microbial therapy. Although gram-positive cocci are the most common causes, fungal infections have been reported, usually in immunocompromised hosts. We present a case of Cladophialophora osteomyelitis in a patient without known immunocompromised that was managed with a Girdlestone pseudoarthroplasty. A 70-year-old male presented to our emergency room with fever, right hip pain, and purulent drainage from a right greater trochanter stage IV decubitus ulcer. His medical history was significant for T10 paraplegia secondary to spinal ependymomas and multiple spinal procedures, as well as significant recent weight loss. Past operations included multiple spinal procedures and repair of a right intertrochanteric femoral fracture with a plate and lateral compression screws. This led to post-operative decubitus ulcer formation over the right greater trochanter, requiring a gracilis flap. The flap remained intact for three years, then re-ulcerated. He subsequently developed femoral head osteomyelitis. To facilitate the treatment, the hardware was removed three weeks prior to presentation. With evidence of worsening osteomyelitis and a new soft-tissue infection, a Girdlestone procedure was performed. Intra-operatively, he was noted to have a pathological intertrochanteric fracture. Soft-tissue cultures yielded Pseudomonas aeruginosa; bone cultures grew Streptococcus dysgalactiae and Cladophialophora spp. Post-operatively, his wound was managed with negative pressure wound therapy with instillation and dwell (NPWTi-d). Delayed primary closure over a drain and topical negative pressure was done four days later. His course was uneventful, and he was discharged six days later. At his four-month follow-up, the wound was completely healed. Invasive fungal infections are rare in immunocompetent individuals. Cladophialophora osteomyelitis has been found in immunocompromised individuals with concomitant cerebral abscesses. To our knowledge, this is the first case of osteomyelitis without previously known immunocompromise.


Dual-biomarker-triggered fluorescence probes for differentiating cancer cells and revealing synergistic antioxidant effects under oxidative stress.
Hydrogen sulfide (H2S) and human NAD(P)H:quinine oxidoreductase 1 (hNQO1) are potential cancer biomarkers and also vital participants in cellular redox homeostasis. Simultaneous detection of these two biomarkers would benefit the diagnostic precision of related cancers and could also help to investigate their crosstalk in response to oxidative stress. Despite this importance, fluorescent probes that can be activated by the dual action of H2S detection and hNQO1 activity have not been investigated. To this end, dual-biomarker-triggered fluorescent probes 1 and 2 were rationally constructed by installing two chemoselective triggering groups into one fluorophore. Probe 1 provides a small turn-on fluorescence response toward H2S but a much larger response to both H2S and hNQO1 in tandem. By contrast, fluorescence probe 2 is activated only in the presence of both H2S and hNQO1. Probe 2 exhibits a large fluorescence turn-on (>400 fold), high sensitivity, excellent selectivity as well as good biocompatibility, enabling the detection of both endogenous H2S and hNQO1 activity in living cells. Bioimaging results indicated that probe 2 could differentiate HT29 and HepG2 cancer cells from HCT116, FHC and HeLa cells owing to the existence of relatively high endogenous levels of both biomarkers. Expanded investigations using 2 revealed that cells could generate more endogenous H2S and hNQO1 upon exposure to exogenous hydrogen peroxide (H2O2), implying the synergistic antioxidant effects under conditions of cellular oxidative stress.


Familial X-linked ichthyosis, steroid sulfatase deficiency, mental retardation, and nullisomy for Xp223-pter.
Steroid sulfatase (STS)-deficient X-linked ichthyosis was diagnosed in a man with short stature and mental retardation. His generation includes five similarly affected male members. A translocation chromosome is segregating in this Newfoundland kindred. The proband's mother and grandmother have normal skin and are of normal intelligence. From his carrier mother, the proband inherited an X short arm (Xp) to Y long arm (Yq) translocation chromosome, with the entire Y short arm and the X short arm terminal segment deleted (Xp223-pter). His cells are completely deficient in STS activity, confirming assignment of the STS locus to Xp223-pter. Effective management of his ichthyosis included treatment with 6% salicylic acid gel under plastic occlusion and removal of the scales by scrubbing.


[Mechanisms of innate and acquired resistance to Trypanosoma cruzicruzi].
Defense mechanisms against the parasite Trypanosoma cruzi, the etiologic agent for dilated myocardiopathy and Chagas disease are reviewed, in vitro studies and experimental models are described and commented. Applying new techniques derived from Molecular Biology for the study of Chagas disease, both at experimental and clinical level could be rewarding and maybe useful to design effective treatment for this irreversible heart disease in humans.


A Survey of Temperature Management Practices Among Burn Centers in North America.
Maintaining body temperature is a unique challenge with burn care. We sought to describe core temperature goals in the operating room (OR) and the methods used to achieve and maintain these goals, along with current methods of warming in the intensive care unit (ICU), the perception of effect of increased ambient temperature on work performance, and concerns with contamination of sterile fields due to increased ambient temperature. A 24 question survey was disseminated to burn centers in the United States and Canada. The questions included demographics, target core and ambient temperatures, warming methods, and beliefs on ambient temperature's effects. Of 121 burn centers, 52 questionnaires were completed (43% response rate). The majority of centers targeted a core temperature between 36 and 38°C in the OR and an ambient temperature between 75 and 95°F in the ICU. The most common methods for maintaining core temperature included warmed ambient temperature, forced air devices, and intravenous fluids. Although the majority of centers reported the belief that increased ambient temperature benefits patients, many also reported that there is a negative impact on staff performance and risk of staff perspiration contaminating sterile fields. Burn centers reported a range of target core temperatures and methods to reach target temperatures. More than a third of respondents perceived a negative impact work performance while more than half acknowledged the potential for contamination of sterile fields. A prospective observational study is needed to determine actual temperature regulation practice patterns and its impact on outcomes.