Monoclonal antibodies against the flagellar fraction of epimastigotes of Trypanosoma cruzi: immunoprotection against metacyclic trypomastigotes obtained by immunization of mice with an affinity-purified antigen.
Subcellular fractions of Trypanosoma cruzi (epimastigotes) were assayed in their capacity to induce protective or aggressive effects in experimental animals. The flagellar fraction showed the best immunoprotective properties without tissular aggression. Monoclonal antibodies were prepared from mice immunized with this fraction. One of them, FCH-F8-4, was able to neutralize the infectivity of bloodstream trypomastigotes, to produce complement-mediated lysis on cell culture-derived trypomastigotes and to recognize the surface of trypomastigotes and epimastigotes by immunofluorescence. FCH-F8-4 reacted in Western blotting with several epimastigote proteins ranging from 50 to 150 kDa, showing a more intense reactivity with 4 bands while it reacted with two molecules on trypomastigote preparations (15 and 48 kDa). Purified antibody was coupled to CNBr-activated Sepharose and used to purify antigens from epimastigote extracts. These antigens were used to immunize BALB/c mice in the presence of Bordetella pertussis as adjuvant. Animals were protected against a challenge with 10(3) metacyclic forms of T. cruzi (Tulahuén strain). Only 40% of immunized mice presented detectable parasites in blood after challenge. Parasitemia decreased 90% in relation to controls in those animals. Survival of immunized mice was 100% in all immunoprotection experiments. These results suggest that the epitope recognized by FCH-F8-4 present in the purified antigens keeps the protective characteristics of flagellar fraction and could be a candidate for the development of a vaccine against T. cruzi infection.


Effects of age and sex on the results of an ankle plantar-flexor manual muscle test.
The ability to perform 20 or more one-leg heel-rises is considered a "normal" grade for muscle strength (force-generating capacity of muscle) of the ankle plantar flexors, regardless of age and sex. Because muscle strength is closely related to age and sex, the "normal" test criterion was re-evaluated in different groups categorized by age and sex. One hundred eighty sedentary volunteers (21-80 years of age) without lower-limb lesions performed as many repetitions of one-leg heel-rise as possible. Lunsford and Perry criteria were used to determine completion of the test. The age and sex of the participants influenced the maximal repetitions of heel-rise, and the repetitions decreased with age and in female subjects. The muscle strength of the ankle plantar flexors, as measured by manual muscle testing, varied with age and sex. Clinicians should consider the variances of age and sex when they perform manual muscle testing of the ankle plantar flexors.


Acteoside inhibits melanogenesis in B16F10 cells through ERK activation and tyrosinase down-regulation.
Acteoside is a phenylpropanoid glycoside extracted from the leaves of Rehmannia glutinosa that displays various biological activities. In this study, we tested the effects of acteoside on tyrosinase activity and melanin biosynthesis in B16F10 melanoma cells. We also explored molecular mechanisms for the inhibition of melanogenesis observed, focusing on the signalling pathway of extracellular signal-regulated kinase (ERK). The effects of acteoside were determined using several cell-free assay systems and B16F10 melanoma cells for melanin content and tyrosinase activity. To investigate effects on melanogenic regulatory factors we performed reverse transcription polymerase chain reaction, cAMP assay and Western blot analyses. Acteoside showed an inhibitory effect on tyrosinase activity and melanin synthesis in both cell-free assay systems and cultured B16F10 melanoma cells. Acteoside decreased levels of tyrosinase, tyrosinase-related protein-1 (TRP-1) and microphthalmia-associated transcription factor (MITF) proteins, whereas it increased ERK phosphorylation. A specific ERK inhibitor, PD98059, abolished the acteoside-induced down-regulation of MITF, tyrosinase and TRP-1 proteins. The ERK inhibitor increased tyrosinase activity and melanin production and reversed the acteoside-induced decrease in tyrosinase activity and melanin content. In addition, acteoside suppressed melanogenesis induced by α-melanocyte-stimulating hormone and showed UV-absorbing effects. Acteoside decreased tyrosinase activity and melanin biosynthesis in B16F10 cells by activating ERK signalling, which down-regulated MITF, tyrosinase and TRP-1 production.


Molecular segregation observed in a concentrated alcohol-water solution.
When a simple alcohol such as methanol or ethanol is mixed with water, the entropy of the system increases far less than expected for an ideal solution of randomly mixed molecules. This well-known effect has been attributed to hydrophobic headgroups creating ice-like or clathrate-like structures in the surrounding water, although experimental support for this hypothesis is scarce. In fact, an increasing amount of experimental and theoretical work suggests that the hydrophobic headgroups of alcohol molecules in aqueous solution cluster together. However, a consistent description of the details of this self-association is lacking. Here we use neutron diffraction with isotope substitution to probe the molecular-scale structure of a concentrated alcohol water mixture (7:3 molar ratio). Our data indicate that most of the water molecules exist as small hydrogen-bonded strings and clusters in a 'fluid' of close-packed methyl groups, with water clusters bridging neighbouring methanol hydroxyl groups through hydrogen bonding. This behaviour suggests that the anomalous thermodynamics of water alcohol systems arises from incomplete mixing at the molecular level and from retention of remnants of the three-dimensional hydrogen-bonded network structure of bulk water.


How using social work can save money under PPS.
PPS calls for every employee to work efficiently together to assure success. This article outlines the various ways social work services can be used to benefit patient care and agency financial and organizational goals. It is a "must read" for clinicians, managers, and administrators to learn more about how social workers can play an increasingly important role in all aspects of the organization.


Combined islet and hematopoietic stem cell allotransplantation: a clinical pilot trial to induce chimerism and graft tolerance.
To prevent graft rejection and avoid immunosuppression-related side-effects, we attempted to induce recipient chimerism and graft tolerance in islet transplantation by donor CD34+hematopoietic stem cell (HSC) infusion. Six patients with brittle type 1 Diabetes Mellitus received a single-donor allogeneic islet transplant (8611 +/- 2113 IEQ/kg) followed by high doses of donor HSC (4.3 +/- 1.9 x 10(6) HSC/kg), at days 5 and 11 posttransplant, without ablative conditioning. An 'Edmonton-like' immunosuppression was administered, with a single dose of anti-TNFalpha antibody (Infliximab) added to induction. Immunosuppression was weaned per protocol starting 12 months posttransplant. After transplantation, glucose control significantly improved, with 3 recipients achieving insulin-independence for a short time (24 +/- 23 days). No severe hypoglycemia or protocol-related adverse events occurred. Graft function was maximal at 3 months then declined. Two recipients rejected within 6 months due to low immunosuppressive trough levels, whereas 4 completed 1-year follow-up with functioning grafts. Graft failure occurred within 4 months from weaning (478 +/- 25 days posttransplant). Peripheral chimerism, as donor leukocytes, was maximal at 1-month (5.92 +/- 0.48%), highly reduced at 1-year (0.20 +/- 0.08%), and was undetectable at graft failure. CD25+T-lymphocytes significantly decreased at 3 months, but partially recovered thereafter. Combined islet and HSC allotransplantation using an 'Edmonton-like' immunosuppression, without ablative conditioning, did not lead to stable chimerism and graft tolerance.


Protective effect of deferoxamine on experimental spinal cord injury in rat.
To observe the protective effect of deferoxamine on experimental spinal cord injury (SCI) in rats. Sprague-Dawley rats were randomly divided into the following four groups. rats were performed laminectomy only; SCI group: rats were performed laminectomy with SCI; DFO group: rats were injected intraperitoneally a bolus of 100mg/kg deferoxamine after SCI; vehicle group: rats were injected intraperitoneally 0.9% saline after SCI. The SCI of animal model was made by using a modified Allen's method on T(10). Six rats of each group were sacrificed at 4h after injured, and the levels of free iron and malondialdehyde (MDA) of involved spinal cord segments were measured by bleomycin assay and the thiobarbituric acid (TBA) separately. The recovery of function was assessed by Modified Tarlov's scale and inclined plane method at 7, 14, 21d after SCI. The histologic changes of the damaged spinal cord were also examined at 7d after SCI. Following SCI, the levels of free iron and MDA were increased significantly and the Modified Tarlov's score and inclined plane angles decreased in SCI group and vehicle group. In DFO group, the levels of free iron and MDA were not increased, but the Modified Tarlov's score and inclined plane angles decreased, the histological findings were improved as well. Deferoxamine can reduce the levels of free iron and lipid peroxidation, and improve the hind limb functional status of rats with spinal cord injury.


Exploratory Analysis of HIV Status Knowledge and Associated Factors Using Data from Electronic Medical Records.
Despite recommendations for the routine HIV testing of all sexually active individuals, a significant percentage of HIV-positive adults are unaware of their HIV status. Therefore, a number of strategies have been implemented to expand HIV testing, which in turn makes it necessary to develop tools for identifying patients with unknown HIV status. This study presents the results of an external validation of an electronic phenotyping algorithm for identifying HIV status and its application on a retrospective cohort in order to explore temporal trends of HIV knowledge status and associated factors.


Liraglutide and cardiovascular outcomes in a real world type 2 diabetes cohort.
In the last years, due to new regulatory guidelines requiring a stringent documentation of cardiovascular (CV) safety of novel drugs for type 2 diabetes, cardiovascular outcomes safety trials (CVOTs) are requested. CVOTs increase the knowledge about the safety profile of the new drugs, but they have intrinsic limits that make difficult their transferability to clinical practice. For this reason, real world evidence is considered an important complement to experimental data. Among the glucagon-like peptide-1 receptor agonists, liraglutide in the LEADER CVOT demonstrated superiority in reducing the risk of major CV events (MACEs) vs. placebo. We conducted an observational, retrospective, longitudinal study based on 307 patients with T2DM treated with liraglutide under routine clinical practice conditions. Real world impact of liraglutide on metabolic control, CV risk factors, hypoglycemia and CV events was assessed. Improvements during 36 months were found in HbA1c (-1.0%; p < 0.0001), fasting blood glucose (-17.6 mg/dL; p < 0.0001), body weight (-3.2 kg; p < 0.0001), waist circumference (-1.45 cm; p = 0.004), systolic blood pressure (-10.41 mmHg; p < 0.0001), diastolic blood pressure (-3.69 mmHg; p < 0.0001), total cholesterol (-7.96 mg/dL; p =0.008) and triglycerides (-20.60 mg/dl; p = 0.01). No severe hypoglycemia occurred. Incidence of MACEs in this cohort was lower than in the LEADER study (2.59 vs. 3.4 events per 100 person-years), confirming CV safety of liraglutide even in the real world. On the other hand, a higher incidence of CV event in patients with established CV disease was documented (8.1 events per 100 person-years), in spite of the use of liraglutide. In conclusion, 36-month durability and CV safety of liraglutide were documented in a real world cohort of T2DM patients, with sustained benefits on a large array of CV risk factors.


Nonlinguistic memory in aphasia.
Two experiments were carried out to assess nonlinguistic memory in aphasia. In the first experiment, subjects had to make judgments about the frequency with which words in a study list were repeated, and, in the second, they had to recall the spatial location in which a pictured object had been presented originally. Aphasics were very accurate in both tasks and did not differ from normal controls. It is suggested that a comprehensive account of memory in aphasia requires that we look beyond their omnipresent language deficit to more general processing factors such as attentional capacity.


A low-intensity lifelong exercise routine changes miRNA expression in aging and prevents osteosarcopenic obesity by modulating inflammation.
Osteosarcopenic obesity (OSO) has been associated with increase immobility, falls, fractures, and other dysfunctions, which could increase mortality risk during aging. However, its etiology remains unknown. Recent studies revealed that sedentarism, fat gain, and epigenetic regulators are critical in its development. One effective intervention to prevent and treat OSO is exercise. Therefore, in the present study, by keeping rats in conditions of sedentarism and others under a low-intensity exercise routine, we established an experimental model of OSO. We determined the degree of sarcopenia, obesity, and osteopenia at different ages and analyzed the miRNA expression during the lifespan using miRNA microarrays from gastrocnemius muscle. Interestingly microarrays results showed that there is a set of miRNAs that changed their expression with exercise. The pathway enrichment analysis showed that these miRNAs are strongly associated with immune regulation. Further inflammatory profiles with IL-6/IL-10 and TNF-α/IL-10 ratios showed that exercised rats presented a lower pro-inflammatory profile than sedentary rats. Also, the body fat gain in the sedentary group increased the inflammatory profile, ultimately leading to muscle dysfunction. Exercise prevented strength loss over time and maintained skeletal muscle functionality over time. Differential expression of miRNAs suggests that they might participate in this process by regulating the inflammatory response associated with aging, thus preventing the development of OSO.


[Renal dysplasias].
The definition and classification of renal dysplasia are discussed, with reference also to its differentiation from kidney heteromorphism.


Public participation in regional health policy: a theoretical framework.
How best to involve the public in local health policy development and decision-making is an ongoing challenge for health systems. In the current literature on this topic, there is discussion of the lack of rigorous evaluations upon which to draw generalizable conclusions about what public participation methods work best and for what kinds of outcomes. We believe that for evaluation research on public participation to build generalizable claims, some consistency in theoretical framework is needed. A major objective of the research reported on here was to develop such a theoretical framework for understanding public participation in the context of regionalized health governance. The overall research design followed the grounded theory tradition, and included five case studies of public participation initiatives in an urban regional health authority in Canada, as well as a postal survey of community organizations. This particular article describes the theoretical framework developed, with an emphasis on explaining the following major components of the framework: public participation initiatives as a process; policy making processes with a health region; social context as symbolic and political institutions; policy communities; and health of the population as the ultimate outcome of public participation. We believe that this framework is a good beginning to making more explicit the factors that may be considered when evaluating both the processes and outcomes of public participation in health policy development.


A new species of Anoplodactylus (Pycnogonida: Phoxichilidiidae) from Brazil, with a case of gynandromorphism in Anoplodactylus eroticus Stock, 1968.
A new species of Anoplodactylus was discovered in coral reefs from the State of Paraíba, northeastern Brazil. A. mirim sp. nov. is very small and is characterized for having 3 teeth on the cheliphores and a very small cement gland. It belongs to the A. pygmaeus complex, which contains very small species. A. batangensis is recorded for the first time along the Brazilian coast, and A. eroticus is recorded for the first time in the South Atlantic. We record the fifth known case of gynandromorphism, the fourth for Anoplodactylus, based on two specimens of A. eroticus.


Systemic low-grade inflammation and depressive symptomology at chronic phase of ischemic stroke: The chain mediating role of fibrinogen and neutrophil counts.
Post-stroke depression (PSD) is the most common psychological consequence of stroke. Increased inflammatory markers resulting from ischemic stroke may played an important role in the pathogenesis of depressive symptomology. The present study was conducted to further elucidate the relationship between stroke severity, systemic low-grade inflammation and chronic phase post-stroke depressive symptomology (CP-PSDS). A total of 897 stroke patients were consecutively recruited in this multicenter prospective cohort study and followed up for 1 year. The analytical sample consisted of 436 patients with ischemic stroke (23.4% female, median age = 57 years) from this cohort. Serum concentrations of inflammatory markers were measured in all 436 patients with ischemic stroke, from fasting morning venous blood samples on admission. Stroke severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) on admission and post-stroke depressive symptomology (PSDS) was evaluated by 17-item Hamilton Rating Scale for Depression (HRSD). In the fully adjusted models, we observed that 1) NIHSS (Model 2: β = 0.200, 95%CI, 0.057 ∼ 0.332), fibrinogen (Model 2: β = 0.828, 95%CI, 0.269 ∼ 1.435), white blood cell counts (WBC, model 2: β = 0.354, 95%CI, 0.122 ∼ 0.577) and neutrophil counts (Model 2: β = 0.401, 95%CI, 0.126 ∼ 0.655) can independently predict the CP-PSDS after ischemic stroke onset; 2) fibrinogen (Indirect effect = 0.027, 95%CI, 0.007 ∼ 0.063, 13.4% mediated), WBC (Indirect effect = 0.024, 95%CI, 0.005 ∼ 0.058, 11.8% mediated) and neutrophil counts (Indirect effect = 0.030, 95%CI, 0.006 ∼ 0.069, 14.8% mediated) could partially mediate the association between stroke severity and CP-PSDS, and 3) stroke severity might cause CP-PSDS partly through the chain-mediating role of both fibrinogen and neutrophil counts (chain mediated effect = 0.003, 95%CI, 0.000 ∼ 0.011, p = 0.025, 1.6% mediated). Findings revealed that fibrinogen, WBC and neutrophil counts may be independent predictors of CP-PSDS and partial mediators of the relationship between stroke severity and CP-PSDS among patients with ischemic stroke. In addition, the chain mediating effect of fibrinogen and neutrophil counts might play an important role in the occurrence of CP-PSDS. However, no inflammatory markers were associated with CP-PSDS in females.


Long-term results of unconstrained Roper-Tuke total elbow arthroplasty in patients with rheumatoid arthritis.
We evaluated the long-term results of 12 unconstrained Roper-Tuke total elbow replacements that were performed in 12 patients with rheumatoid arthritis from 1983 to 1989. The mean follow-up period was 9.5 years (range 8 to 13 years). We used the Ewald elbow-scoring system to chart results. This showed that the scores for the 12 elbows had improved from an average preoperative score of 39 points (range 17 to 72 points) to an average postoperative score of 80 points (range 45 to 97 points). The greatest improvements were in terms of pain relief, function, and range of motion. Eight elbows were free of pain by the end of follow-up. Average elbow flexion increased from 115 degrees before operation to 140 degrees after operation, and pronation and supination increased from 52 degrees to 61 degrees and 42 degrees to 71 degrees, respectively. Radiographs of the 12 elbows showed constant wear of the ulnar polyethylene with loosening of 2 ulnar components. Revision of the prosthesis was necessary in 2 elbows because of aseptic loosening. Complications included 1 subluxation, 1 supracondylar fracture, and 2 ulnar neuropathies. Despite some excellent clinical results with a follow-up of over 10 years, the authors no longer recommend the use of this kind of elbow prosthesis in patients with rheumatoid arthritis because of the high complication rate and the impossibility of adapting this implant in the event of bone loss. The authors propose a new classification of humeral bone loss that will allow for better planning of primary and revision total elbow arthroplasties.


Rabbit major histocompatibility complex. IV. Expression of major histocompatibility complex class II genes.
The rabbit MHC class II DP, DQ, and DR alpha and beta chain genes were transfected into murine B lymphoma cells. The transfected cells expressed R-DQ and R-DR molecules on the cell surface but they did not express the R-DP genes either on the cell surface or at the level of mRNA. Northern blot analyses showed that the R-DP genes were expressed, albeit at low levels, in rabbit spleen. Similar analyses showed that the R-DQ and R-DR genes were expressed at high levels in rabbit spleen. A new monoclonal anti-rabbit class II antibody, RDR34, has been developed and shown to react with the R-DR transfected cells and not with the R-DQ transfected cells. The previously described monoclonal anti-rabbit class II antibody, 2C4, reacted with the R-DQ transfected cells and not with the R-DR transfected cells. Thus, 2C4 and RDR34 MAb's are specific for the R-DQ and R-DR molecules, respectively. Each of the antibodies reacted with approximately 50% of rabbit spleen cells as shown by immunofluorescent antibody studies.


Antioxidant properties of bio-active substances from shrimp head fermented by Bacillus licheniformis OPL-007.
Antioxidative activities were found in the culture supernatant of Bacillus licheniformis OPL-007 using shrimp head waste (SHW) as the sole carbon and nitrogen source. After optimizing fermentation conditions, some bio-active substances were determined from the broth. The contents of total phenols, polysaccharides, reducing sugars, free amino acids, and organic acids were 888.80, 402.74, 85.88, 2,061.79, and 5,426.74 mg/l, respectively. Moreover, the fermentation liquid was found rich in eight essential amino acids and non-protein amino acids. The antioxidant activity of the culture supernatant, in terms of the scavenging activity of DPPH radicals, reducing power, and metal chelating ability, was monitored, and the fermentation liquid showed a strong antioxidant capacity. The results indicate that bio-deproteinization of SHW by B. licheniformis OPL-007 can increase its antioxidant activity, and SHW has the potential application in the production of functional foods.


Herpes simplex virus reactivation and dental procedures.
Dental extraction is reported to trigger recurrent herpes labialis (RHL). This aims to prospectively study the clinical occurrence of RHL and the oral herpes simplex virus type 1 (HSV-1) viral shedding before and 3 days after different dental procedures. Oral HSV-1 DNA was measured by real-time PCR before and 3 days after dental procedures of the inferior dentition in 57 immunocompetent patients (mean age 32.4 years) who were selected and divided into four distinct subgroups (dental inspection without anesthesia, n = 19; dental filling under local anesthesia, n = 14; molar extraction under local anesthesia, n = 15; and molar extraction under general anesthesia, n = 9) and compared to 32 healthy controls (mean age 33 years). None of the patients suffered from RHL at day 3. Oral HSV-1 DNA was detected before and after procedure in 1.7 % (1/57) and 5.3 % (3/57), respectively [dental inspection without anesthesia, 5.3 % (1/19); molar extraction under local anesthesia, 6.7 % (1/15); and molar extraction under general anesthesia, 11 % (1/9)]. None of the controls presented RHL or detectable oral HSV-1 DNA. There was no statistically significant difference between the study groups and controls. Molar extraction increases the risk of oral HSV-1 shedding but not of RHL. Procedure-related nerve damage probably accounts for HSV reactivation. Antiviral prophylaxis for RHL is not routinely recommended for dental procedures, regardless of a prior history of RHL.


The ameliorative effects of Lactobacillus coagulans and Lactobacillus casei probiotics on CCl4-induced testicular toxicity based on biochemical, histological and molecular analyses in rat.
Probiotics are commonly present in foods and role as dietary adjuncts and alternatives to pharmacological products in many medical fields. The aim of this study was to investigate the effects of Lactobacillus coagulans and Lactobacillus casei probiotics on carbon tetrachloride (CCl4 )-induced reproductive injury and sperm toxicity in rats. Thirty-two Wistar rats were divided into four groups as follows: sham, CCl4 (2 ml/kg), L. casei probiotic + 2 ml/kg CCl4 and L. coagulans probiotic + 2 ml/kg CCl4 . On the 36th day after the intervention, serum levels of follicle-stimulating hormone (FSH), luteinising hormone (LH) and total testosterone (T), as well as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, were measured. Testicular malondialdehyde (MDA) level, the expressions of apoptosis-related genes (Bcl-2 and Bax), Bax/Bcl-2 ratio, histomorphometric indices such as tubular differentiation index (TDI), repopulation index (RI), spermiogenesis index (SPI) and sperm parameters were evaluated. L. casei and L. coagulans probiotics improved the levels of reproductive hormones and antioxidant capacity in rats. Both the probiotics, especially L. casei, increased the rate spermatogenesis which accompanied with significant increments in testicular TDI, RI and SPI. Furthermore, both probiotics down-regulated Bax and up-regulated Bcl-2, following by decreased Bax/Bcl-2 ratio. Our key findings indicated that L. casei and L. coagulans have protective effects against CCl4 -induced testicular toxicity.


Sonochemical degradation of cyclic nitroxides in aqueous solution.
The sonochemical degradation of eight five- and six-membered nitroxides has been studied by EPR spectroscopy after exposure to ultrasound at a frequency of 354 kHz in argon-saturated aqueous solution. Concentration vs. time profiles do not follow a simple rate law. Octanol/water partition functions have been determined for all eight nitroxides, and an excellent linear correlation has been found between initial decomposition rates and hydrophobicity (log K(octanol/water)). Variation of initial rate with concentration was investigated for one compound (TEMPONE) and is largely consistent with an equilibrium distribution of substrate between bulk solution and the gas/liquid interface.


Pseudomyxoma peritonei: some different sonographic findings.
The purpose of our study was to assess the sonographic features of pseudomyxoma peritonei (PMP). All records of peritoneal biopsies under the guidance of ultrasound in our institutional database from April 2007 to June 2011 were retrospectively reviewed. 19 cases of PMP and 279 cases of other peritoneal lesions were included in the study. The sonograms of peritoneum, ascites, and parenchymal organs involved by PMP were evaluated, respectively, and compared with sonograms of other peritoneal lesions. Anechoic areas were found in 89.5% cases of PMP at high frequency of insonation and the sensitivity in indicating PMP was 100%. In the pelvic cavity, echogenic foci in ascites of PMP in 52.6% cases were mobile. The specificity of "starburst" appearance and sensitivity of scalloping of the liver margin were relatively high (82.3 and 88.1%), but the sensitivity and specificity (57.9 and 42.1%) of these two signs were relatively low. Anechoic area in the thickened peritoneum was a specific sign in indicating the diagnosis of PMP and high-frequency transducer could reveal these tiny anechoic areas more explicitly. In the pelvic cavity, echogenic foci in ascites of PMP could be observed to be mobile and scalloping of the liver margin and "starburst" appearance also played a significant role in indicating PMP.


Perspectives on Patient Access to Radiation Oncology Services in South America.
Cancer represents a fast-growing challenge worldwide, and is being recognized as an emerging and critical issue in low- and middle-income countries, such most of South America. This subcontinent is unique for its geography, culture, and ethnical diversity. Most of its countries have large expanses of jungle and desert where underserved population groups including indigenous (native Indians), represent a challenge for cancer care. Many indigent patients have no access to preventive care nor early diagnosis. This results in late presentations with advanced disease and frequently incurable cancer. Prompt and coordinated action from local and international organizations is needed to support and guide local governments to avoid a global crisis. The critical role of education to improve awareness of the importance of radiation therapy, a cost-effective treatment modality, with the potential to help these patients at a relatively low cost is discussed.


Synthesis and anticancer activity evaluation of 7-oxygen-substituted and 8,17-epoxydized 1,2-didehydro-3-ox-14-deoxyandrographolide derivatives.
Two novel series of 1,2-didehydro-7-hydroxy-3-ox-14-deoxyandrographolide and 1,2-didehydro-8,17-epoxy-3-ox-14-deoxyandrographolide derivatives were designed, synthesized and evaluated for their cytotoxic activity in vitro against two human cancer cell lines HCT-116 (human colon cancer) and MCF-7 (human breast cancer). Most tested compounds, especially those of the first series, displayed better inhibitory activity on both HCT-116 and MCF-7 cells than andrographolide. HCT-116 cells were found to be more sensitive to tested compounds than MCF-7, and compound 13b exhibited the most potent activity against HCT-116, with an IC50 value of 7.32 μM. Further anti-cancer mechanistic investigation demonstrated that compound 13b effectively suppressed the growth of HCT-116 cells by triggering early and late cellular apoptosis in a concentration-dependent manner and arresting cell cycle in S phase.


A wavelet gradient sparsity based algorithm for reconstruction of reduced-view tomography datasets obtained with a monochromatic synchrotron-based X-ray source.
High-resolution synchrotron computed tomography (CT) is very helpful in the diagnosis and monitor of chronic diseases including osteoporosis. Osteoporosis is characterized by low bone mass and cortical bone porosity best imaged with CT. Synchrotron CT requires a large number of angular projections to reconstruct images with high resolution for detailed and accurate diagnosis. However, this poses great risks and challenges for serial in-vivo human and animal imaging due to a large amount of X-ray radiation dose required that can damage living specimens. Also, longer scan times are associated with increased risk of specimen movement and motion artifact in the reconstructed images. We developed a wavelet-gradient sparsity based algorithm to be utilized as a synchrotron tomography reconstruction technique allowing accurate reconstruction of cortical bone porosity assessed for in-vivo preclinical study which significantly reduces the radiation dose and scan time required while maintaining satisfactory image resolution for diagnosis. The results of our study on a rat forelimb sample imaged in the Biomedical Imaging and Therapy Bending Magnet (BMIT-BM) beamline at the Canadian Light Source show that the proposed algorithm can produce satisfactory image quality with more than 50 percent X-ray dose reduction as indicated by both visual and quantitative-based performance.


Effects of second-line antihyperglycemic drugs on the risk of chronic kidney disease: applying a target trial approach to a hospital-based cohort of Thai patients with type 2 diabetes.
The reno-protective effect of second-line treatments in type 2 diabetes has been assessed by clinical trials but generalizability to routine clinical practice is still uncertain. We aimed to assess the effectiveness of these treatments, when added to metformin, on the risk of chronic kidney disease (CKD). A real-world, hospital-based, type 2 diabetes cohort was retrospectively assembled at Ramathibodi Hospital from 2010 to 2019. Patients who received sulfonylureas (SU), thiazolidinediones (TZD), dipeptidyl peptidase-4 inhibitors (DPP4i), or sodium-glucose cotransporter-2 inhibitors (SGLT2i), as second-line antihyperglycemic treatment were included. Treatment effect models with inverse probability weighting and regression adjustment were used to estimate CKD risk according to treatment. CKD was identified in 4,132 of the 24,777 patients with type 2 diabetes (16.7%). The CKD incidence (95% CI) was 4.1% (2.2%, 6.9%), 13.5% (12.5%, 14.6%), 14.8% (13.5%, 16.1%), and 18.0% (17.4%, 18.5%) for patients receiving SGLT2i, DPP4i, TZD, and SU treatment, respectively. The average treatment effects (i.e., the difference in CKD risk) for SGLT2i, DPP4i, and TZD compared to SU were - 0.142 (- 0.167, - 0.116), - 0.046 (- 0.059, - 0.034), and - 0.004 (- 0.023, 0.014), respectively, indicating a significant reduction in CKD risk of 14.2% and 4.6% in the SGLT2i and DPP4i groups, respectively, compared to the SU group. Furthermore, SGLT2i significantly reduced CKD risk by 13.7% (10.6%, 16.8%) and 9.5% (6.8%, 12.2%) when compared to TZD and DPP4i, respectively. Our study identified 14.2%, 13.7%, and 9.5% reduced CKD risk in Thai patients with type 2 diabetes who were treated with SGLT2i compared to those treated with SU, TZD, and DPP4i, respectively, in real-world clinical data. Previous evidence of a reno-protective effect of SGLT2i reported in other populations is consistent with our observations in this Southeast Asian cohort.


Validation of the Czech Version of the Voice Handicap Index.
The present study aims to evaluate the reliability and construct validity of the Czech version of the Voice Handicap Index (VHI-CZ) and determine the cut-off value to distinguish dysphonic patients from nondysphonic individuals. Prospective study, Parallel group design. The study investigated 100 adult patients with dysphonia, divided into three groups based on the etiology of the voice problem (neurogenic, functional, and structural). Out of these, 25 patients were used for test-retest analysis, and 45 patients to determine the responsiveness to change. The control group consisted of 51 healthy subjects. All 151 individuals completed the VHI-CZ and were examined with the videolaryngostroboscopy. The internal consistency (Cronbach's alpha), the test-retest reliability (Intra-class Correlation Coefficient, ICC), and the construct validity were analyzed and the normative cut-off value was determined. The internal consistency of the VHI-CZ was excellent (Cronbach α = 0.984), and test-retest reliability was also excellent (ICC = 0.95, P < 0.001). The correlation between the self-assessed severity of the voice disorder and the VHI-CZ score was strong (Spearman's ρ = 0.877, P < 0.001). The VHI scores differences between dysphonic and nondysphonic patients were statistically significant (Mann-Whitney U test, P < 0.001). The differences among the three etiological subgroups (neurogenic, functional, and structural) were also statistically significant (Kruskal-Wallis test, P < 0.001). Moreover, the differences in the VHI-CZ total scores between pretreatment and posttreatment were statistically significant (Wilcoxon test, P < 0.001). The cut-off score of 13 points was found, by the analysis of the Receiver Operating Characteristic (ROC, Youden Index), to be most suitable for preselecting dysphonic individuals. The existing VHI-CZ showed excellent reliability and construct validity. The Czech VHI is a useful and valid monitoring tool for clinicians.


The post-prandial state in Type 2 diabetes and endothelial dysfunction: effects of insulin aspart.
Recently, much attention has been focused on the possibility that the post-prandial state may be a cardiovascular risk factor in diabetes. The aim of the present study was to evaluate whether the post-prandial state is associated with endothelial dysfunction in patients with diabetes and to explore the effect on this aspect of managing post-prandial hyperglycaemia by insulin aspart. Twenty-three patients with Type 2 diabetes and 10 normal controls were recruited. In the diabetic patients two different tests were performed in each subject: a standard meal preceded by subcutaneous injection of soluble insulin (0.15 U/kg body weight) or of short-acting insulin aspart (0.15 U/kg body weight). These tests were designed to achieve different levels of post-prandial hyperglycaemia. Controls received a single standard meal test. Immediately before, and 1, 2, 4 and 6 h after each meal, blood glucose, triglycerides, free fatty acids and flow-mediated vasodilation were measured. Compared with regular insulin, insulin aspart significantly reduced the area under the curve for post-prandial hyperglycaemia (58.3 +/- 17.6 vs. 68.1 +/- 17.7; P<0.04), and preserved flow-mediated vasodilation, which was decreased in the post-prandial state (39.4 +/- 2.9 vs. 34.1 +/- 2.2; P<0.01). Triglyceride and free fatty acid levels were not differentially affected by the treatment. In normal controls the meal did not affect flow-mediated vasodilation. This study shows that the post-prandial state is accompanied by endothelial dysfunction in Type 2 diabetic patients and that insulin aspart improved endothelial function.


On the development of the cerebellum of the trout, Salmo gairdneri. I. Patterns of cell migration.
Patterns of cell migration in the cerebellum of Salmo gairneri RICHARDSON, 1836 were studied in fish ranging in length from 4.5 to 230 mm. Sagittal and transverse series were stained with haematoxylin-eosin or according to Nissl or Golgi. The cerebellum of the trout comprises three main parts, i.e. the massive corpus cerebelli, the folded valvula cerebelli and the transversely oriented lobus vestibulolateralis. The early cerebellar anlage is a simple plate, which is delimited from the tectum mesencephali by the fissura rhombo-mesencephalica. The histogenesis may be divided into three phases. During the first phase the matrix layer produces the mantle layer. During the second phase the three typical cerebellar layers are formed. The third phase is characterized by growth. As regards the first phase, the mantle layer develops throughout almost the entire extent of the cerebellar anlage. Only in a narrow paramedian strip (matrix zone M) this layer does fail to appear. In regions where the mantle layer is formed, the matrix no longer occupies the whole width of the wall and is termed the ventricular matrix. The largest part of the ventricular matrix is gradually exhausted. However, in some places this matrix persists as a layer of proliferating cells. This holds for the matrices of the caudal border of the cerebellum; matrix zone L, surrounding the lateral recesses of the fourth ventricle, and matrix zone P, connecting the matrix zones L. The mantle layer produced in the first phase of histogensis mainly develops into the ganglionic layer. The second phase of histogenesis is characterized by the formation of a secondary matrix. Newly produced cells of the matrix zones M, L and P migrate away from their sites of origin towards the regions where a mantle layer prevsiously has been formed. The majority of these cells develops into granule cells. Migration of the cells produced in the first phase of histogenesis occurs in the radial direction. Because of the curvature of the cerebellum this direction changes with respect to the main longitudinal axis of the brain from region to region. The migration paths of granule cells show variable directions, namely (a) tangential followed by radial, for granule cells in the corpus cerebelli and in the medial parts of the valvula cerebelli and the lobus vestibulolaterialis, (b) tangential, for granule cells in the lateral parts of the valvula and (c) radial, for granule cells in the lateral parts of the lobus vestibulolateralis. The analysis of these migration patterns elucidates both the histogenesis and the morphogenesis of the cerebellum of the trout.


A search for human T-cell leukemia virus type I in the lesions of patients with tropical spastic paraparesis and polymyositis.
We searched for the presence of human T-cell leukemia virus type I (HTLV-I) sequences in central nervous system and muscle lesions of 3 patients with tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM) and 3 patients with HTLV-I-associated polymyositis. Proviral DNA coding for the Tax protein was found by polymerase chain reaction amplification in DNA extracted from lesions of every patient with TSP/HAM or HTLV-I-associated polymyositis. In contrast, viral RNA was found occasionally by in situ hybridization in muscle lesions of some patients with polymyositis, but was never found in central nervous system lesions of TSP/HAM patients.


Gestational age at preterm premature rupture of membranes: a risk factor for neonatal white matter damage.
Gestational age at delivery and spontaneous prematurity are independent risk factors for white matter damage (WMD). However, among infants delivered spontaneously after preterm premature rupture of membranes (PPROM), latency of PPROM has been inconsistently correlated with risk of WMD. We have explored whether gestational age at membrane rupture is independently associated with WMD. Using a cohort of 196 liveborn singleton nonanomalous neonates born at 24.0 to 33.6 weeks from January 1993 to December 2002 after pPROM and who survived 7 days, we compared the characteristics of those who developed WMD (n = 15) with those who did not (n = 181) using Fisher exact test, Student t test, and logistic regression analysis, with a 2-tailed P < .05 or odds ratio (OR) with 95% CI not inclusive of the unity considered significant. Stepwise logistic regression analysis demonstrated that gestational age at PPROM (P < .001, OR 0.79) was significantly associated with WMD. The association was independent of corticosteroid administration (P = .016), latency interval (P = .69), gestational age at delivery (P = .99), and birth weight (P = .62). Among premature infants born at <34 weeks after pPROM, gestational age at diagnosis is independently associated with WMD.


Using TNM staging to predict survival in patients with squamous cell carcinoma of head & neck.
There is a need for a classification system for prognosis based on the TNM system for patients with squamous cell carcinoma of the head and neck such that patient groupings are homogeneous within and heterogeneous between. Six hundred fifty-five consecutive patients with invasive squamous cell carcinoma of the head and neck followed prospectively are split into a training set and a test set. Using the training set, the Cox Proportional Hazards Model and the outcome of dead with disease, we created homogeneous prognostic levels (PLs) based on RR. Using the test set, we compare our model to others in the literature. Using the training set, we identified five PLs, and using the test set, we demonstrated that our model is superior to others for both within-group homogeneity and between-group heterogeneity. A simple classification system can be used to group patients for survival and is valid for future study in prognostication.


Real-time PCR for rapidly detecting aniline-degrading bacteria in activated sludge.
We developed a detection method that uses quantitative real-time PCR (qPCR) and the TaqMan system to easily and rapidly assess the population of aniline-degrading bacteria in activated sludge prior to conducting a biodegradability test on a chemical compound. A primer and probe set for qPCR was designed by a multiple alignment of conserved amino acid sequences encoding the large (α) subunit of aniline dioxygenase. PCR amplification tests showed that the designed primer and probe set targeted aniline-degrading strains such as Acidovorax sp., Gordonia sp., Rhodococcus sp., and Pseudomonas putida, thereby suggesting that the developed method can detect a wide variety of aniline-degrading bacteria. There was a strong correlation between the relative copy number of the α-aniline dioxygenase gene in activated sludge obtained with the developed qPCR method and the number of aniline-degrading bacteria measured by the Most Probable Number method, which is the conventional method, and a good correlation with the lag time of the BOD curve for aniline degradation produced by the biodegradability test in activated sludge samples collected from eight different wastewater treatment plants in Japan. The developed method will be valuable for the rapid and accurate evaluation of the activity of inocula prior to conducting a ready biodegradability test.


Lipid and lipoprotein levels in undialyzed patients with chronic renal failure.
Lipid and lipoprotein levels were measured in undialyzed uremic men and compared with levels of healthy control subjects. The patients had lower high-density lipoprotein (HDL) cholesterol (mean +/- SD, 46.3 +/- 14.8 vs 54.1 +/- 18.2 mg/dl) and increased serum triglycerides (197 +/- 151 vs 142 +/- 87.7 mg/dl). When compared with patients maintained on dialysis, the undialyzed patients had higher HDL cholesterol (46.3 +/- 14.8 vs 30.3 +/- 13.3 mg/dl), serum cholesterol (226 +/- 81 vs 151 +/- 42 mg/dl), and triglycerides (197 +/- 151 vs 146 +/- 105 mg/dl). The low-density lipoprotein (LDL): high-density lipoprotein cholesterol ratios were 3.78, 3.24, and 2.84 in the dialyzed, undialyzed, and control groups, respectively. Lecithin: cholesterol acyl transferase activity of undialyzed patients was similar to controls when measured by an endogenous substrate assay (148 +/- 112 vs 112 +/- 28 nmol/ml/hr), but were significantly lower when assayed using exogenous substrate (73.3 +/- 25.6 vs 112.8 +/- 7 nmol/ml/hr). The rate of cholesterol transfer (RCT) from HDL to very low density lipoprotein and LDL was in the following order: dialyzed patients (1.85 +/- 1.29 mg/dl/hr) less than undialyzed patients (2.41 +/- 1.57 mg/dl/hr) less than control subjects (4.83 +/- 3.13 mg/dl/hr). Within the undialyzed patient group, black patients had lower serum cholesterol and triglycerides and higher HDL and HDL3 cholesterol than white patients. Apoprotein A-I levels were higher and apoprotein B levels were lower in the black patients. There was a strong correlation (r = 0.9501) between apoprotein A-I and HDL levels in the black patients, but not in the white patients (r = -0.148).(ABSTRACT TRUNCATED AT 250 WORDS)


Rigorous analysis of the topologically protected edge states in the quantum spin Hall phase of the armchair ribbon geometry.
Studying the edge states of a topological system and extracting their topological properties is of great importance in understanding and characterizing these systems. In this paper, we present a novel analytical approach for obtaining explicit expressions for the edge states in the Kane-Mele model within a ribbon geometry featuring armchair boundaries. Our approach involves a mapping procedure that transforms the system into an extended Su-Schrieffer-Heeger model, specifically a two-leg ladder, in momentum space. Through rigorous derivation, we determine various analytical properties of the edge states, including their wave functions and energy dispersion. Additionally, we investigate the condition for topological transition by solely analyzing the edge states, and we elucidate the underlying reasons for the violation of the bulk-edge correspondence in relatively narrow ribbons. Our findings shed light on the unique characteristics of the edge states in the quantum spin Hall phase of the Kane-Mele model and provide valuable insights into the topological properties of such systems.


Clinical joints manifestations in patients with psoriatic arthritis on musculoskeletal ultrasound.
To investigate the clinical joints manifestations under musculoskeletal ultrasound (MSUS) and hematological findings in patients with psoriatic arthritis (PsA), which may provide a basis for improving the early diagnosis of PsA. From September 2016 to February 2021, 328 patients with psoriasis visited the dermatological and rheumatic outpatient of the Beijing Friendship Hospital were enrolled in this retrospective study. Patients were enrolled according to a paired-design method. The PsA group included 164 patients diagnosed with PsA, and the control group included 164 patients diagnosed with psoriasis without PsA. Both groups of patients were evaluated by a rheumatoid immunologist, a dermatologist, and a sonographer. Demographic data, course of disease, severity of skin lesions, combined diseases, and previous treatment were all collected. All patients received MSUS and blood examinations. Lower extremity enthsis diseases were evaluated by Glasgow ultrasound enthesitis scoring system (GUESS). In the comparison of baseline clinical characteristics, the PsA group has longer course of psoriasis (P = 0.005), longer course of joints pain (P = 0.035), higher incidence of peripheral joints pain (P = 0.001), higher GUESS score (P < 0.001), and higher incidence of involved nails or toenails (P = 0.036) The most common joints involved were proximal interphalangeal joint (33.5%), knee (27.4%), and metacarpophalangeal joint (25.0%). Differences in clinical manifestations at different lower limb enthesitis on MSUS have also been proved. The positive incidences of rheumatoid factor (RF) (P = 0.002) and anti-cyclic citrullinated peptide (CCP) antibody (P < 0.001) in the PsA group were significantly higher than those in the control group. Binary Logistic regression showed that patients with anti-CCP antibody positive had a higher risk of active PsA compared to patients with negative antibodies in PsA group (OR: 0.626, 95%CI: 0.361-0.792, P < 0.05). In conclusion, the most common joints involved were proximal interphalangeal joint, knee, and metacarpophalangeal joint in patients with PsA, and the common types of diseased joints manifestations on MSUS were synovial thickening, fluid accumulation, bone destruction, increased blood flow signals, and attachment site inflammation. GUESS scoring systems can be used to identify PsA in patients with psoriasis. Psoriasis patients with RF and anti-CCP antibody positive were more likely to develop PsA, and anti-CCP antibody positive was a risk factor for active PsA. • GUESS scoring systems can be used to identify PsA in patients with psoriasis. • Psoriasis patients with RF and anti-CCP antibody positive were more likely to develop PsA, and anti-CCP antibody positive was a risk factor for active PsA.


Risk Factors for Blindness in Children With Primary Congenital Glaucoma-Follow-up of a Registry Cohort.
To evaluate the baseline features associated with blindness in a cohort of children with primary congenital glaucoma (PCG) from a hospital registry. Retrospective clinical cohort study. Setting: Observational cohort study. StudyPopulation: The registry included all children who presented to our tertiary care institute between 1995 and 2014 with a diagnosis of childhood glaucoma. ObservationProcedure: Baseline characteristics at initial presentation of children with PCG in the registry who were blind at the last follow-up were compared with those who were not blind, using bivariate and then multivariate regressions to account for potential confounders. MainOutcomeMeasures: Blindness was defined as a best-corrected visual acuity of 3/60 (20/400) or worse in the better eye at the final follow-up. The eligible sample consisted of 196 children with a mean age of 9.54 ± 22.44 months at presentation. After a mean ± standard deviation follow-up of 8.49 ± 3.85 years, 20 (10.2%) children were blind. The baseline demographic factors, intraocular pressure, horizontal corneal diameter, spherical equivalent, axial length, and corneal thickness, were similar for the "blind" and "not blind" groups (P > .05). In the multivariate regression, only the severity of corneal opacification remained significantly (P < .001) associated with the risk of blindness (odds ratio = 4.05; 95% confidence interval: 1.89-8.85). Corneal clouding is a predictor of future blindness in children with PCG. Children with severe corneal clouding may need more aggressive intraocular pressure control, closer follow-up, and earlier counseling.


The importance of good history taking: a case report.
Early comprehensive geriatric assessment (CGA) with good history-taking is essential in assessing the older adult. Our patient, a 75-year-old Caucasian woman, was originally admitted to hospital for investigation of iron deficiency anemia. During admission, she developed pneumonia and new intermittent atrial fibrillation in association with a right-sided weakness, which was felt to be new at the time. Following this episode, she was treated for a further chest infection and, despite clinical improvement, her inflammatory markers failed to settle satisfactorily. She was transferred to her local hospital for a period of rehabilitation where further neurological findings made the diagnosis of solely stroke questionable; these findings prompted further history-taking, investigations and input from other disciplines, thereby helping to arrive at a working diagnosis of vasculitic neuropathy. The case aims to highlight the importance of taking a good history and performing an early comprehensive assessment in the older adult.


The structure of an antigenic determinant in a protein.
The immunogenic and antigenic determinants of a synthetic peptide and the corresponding antigenic determinants in the parent protein have been elucidated. Four determinants have been defined by reactivity of a large panel of antipeptide monoclonal antibodies with short, overlapping peptides (7-28 amino acids), the immunizing peptide (36 amino acids), and the intact parent protein (the influenza virus hemagglutinin, HA). The majority of the antipeptide antibodies that also react strongly with the intact protein recognize one specific nine amino acid sequence. This immunodominant peptide determinant is located in the subunit interface in the HA trimeric structure. The relative inaccessibility of this site implies that antibody binding to the protein is to a more unfolded HA conformation. This antigenic determinant differs from those previously described for the hemagglutinin and clearly demonstrates the ability of synthetic peptides to generate antibodies that interact with regions of the protein not immunogenic or generally accessible when the protein is the immunogen.


Flow-injection electrochemical determination of citric acid using a cobalt(II)-phthalocyanine modified carbon paste electrode.
The electrocatalytic activity of cobalt(II)-phthalocyanine immobilized in a carbon paste electrode for citric acid oxidation under a diffusion-controlled electrochemical process was employed to develop a selective flow injection amperomettric analysis method. Under optimized conditions, rapid and reliable determinations of citric acid (65 samples per hour) were achieved for analyses of commercial fruit juices with minor pretreatment of the samples. A linear response was accomplished ranging from 0.25 to 15 mmol L(-1) (r(2)=0.9979) with an estimated detection limit of 0.117 mmol L(-1). Alternatively, a very sensitive and selective assay was developed for the micromolar range, obtaining a linear response ranging from 3.81 to 91.2 μmol L(-1) (r(2)=0.9993) with an estimated detection limit of 2.54 μmol L(-1), by using square wave voltammetric methodology. The speed and simplicity of the proposed approaches compares advantageously to the all other citric acid determination methods.


The role of CA 125 in the evaluation of palpable or enlarged postmenopausal ovaries.
A serum CA 125 assay provided a method of more accurately identifying a postmenopausal woman at high risk for ovarian cancer when a screening ultrasound examination revealed a 2 X 3 cm ovary that could not be detected by palpation.


Electron microscopy of developing calvaria reveals images that suggest that osteoclasts engulf and destroy osteocytes during bone resorption.
It is generally accepted that osteoclasts are responsible for the breakdown and removal of bone matrix constituents. However, very little is known about the fate of osteocytes during bone resorption. In the present study we have examined sites of bone destruction in calvaria of young rats aged 4-9 days in the hope of obtaining information on the fate of osteocytes. Decalcified glutaraldehyde-formaldehyde-fixed specimens were prepared for ultrathin section electron microscopy. When sequentially arranged, the images obtained suggest that osteoclasts engulf and destroy osteocytes during bone degradation. We propose that the following sequence of events takes place when a lacuna is opened up by an osteoclast: (1) When the osteoclast comes in contact with an osteocyte, the villi of the ruffled border become flat and broad. (2) Long osteoclastic extensions surround the osteocyte. (3) The osteocyte is subsequently internalized with apparent degradation.


Novel functions of tyrosine kinase 2 in the antiviral defense against murine cytomegalovirus.
We have recently reported that tyrosine kinase 2 (Tyk2)-deficient mice have a selective defect in the in vivo defense against certain viruses. In our current study we show that Tyk2 is essential for the defense against murine CMV (MCMV). In vivo challenges with MCMV revealed impaired clearance of virus from organs and decreased survival of mice in the absence of Tyk2. Our in vitro studies demonstrate that MCMV replicates to dramatically higher titers in Tyk2-deficient macrophages compared with wild-type cells. We show an essential role of type I IFN (IFN-alphabeta) in the control of MCMV replication, with a prominent role of IFN-beta. MCMV infection leads to the activation of STAT1 and STAT2 in an IFN-alphabeta receptor 1-dependent manner. Consistent with the role of Tyk2 in IFN-alphabeta signaling, activation of STAT1 and STAT2 is reduced in Tyk2-deficient cells. However, lack of Tyk2 results in impaired MCMV-mediated gene induction of only a subset of MCMV-induced IFN-alphabeta-responsive genes. Taken together, our data demonstrate a requirement for Tyk2 in the in vitro and in vivo antiviral defense against MCMV infection. In addition to the established role of Tyk2 as an amplifier of Jak/Stat signaling upon IFN-alphabeta stimulation, we provide evidence for a novel role of Tyk2 as a modifier of host responses.


A less irritant norcantharidin lipid microspheres: formulation and drug distribution.
Lipid microspheres (LM) have recently been used as intravenous (i.v.) carriers for drugs, which are sufficiently soluble in oil. However, in the case of norcantharidin (NCTD), which is poorly soluble in both the water and oil phases, this approach is not feasible. In this study, NCTD-loaded LM was prepared by transferring the drug to the interfacial surface of the oil and aqueous phases to produce a less irritating i.v. formulation of NCTD. A probe type sonicator was used to disperse NCTD into the oil phase together with lecithin and Tween 80. A high-pressure homogenization process was used to prepare the lipid microspheres and localize the drug at the surfactant layer. The LM loaded with NCTD consisted of 0.02% drug. Characterization of LMs and short-term stability was performed by photon correlation spectroscopy (PCS) and a centrifugation test was also carried out. The results showed that NCTD-loaded LM (2 mg/ml) with over 80% NCTD loaded in the interfacial surface were stable for a period of 2 months, and were suitable for i.v. injection in terms of size and stability, whether be diluted or not. Such formulations produced less pain and irritation in animal studies.


The use of a continuous brachial plexus catheter to facilitate inpatient rehabilitation in a pediatric patient with refractory upper extremity complex regional pain syndrome.
The goal of interventional management of refractory pediatric complex regional pain syndrome is to facilitate early restoration of function to the affected extremity. These interventions are more complicated in children, as most do not tolerate these procedures without sedation. We report the first detailed description of a pediatric patient with complex regional pain syndrome refractory to medical management who had complete resolution of symptoms after brief inpatient rehabilitation involving continuous brachial plexus blockade and a multidisciplinary apaproach. Repeated interventional therapy for refractory, severe complex regional pain syndrome may not be feasible in children owing to the requirement for deep sedation or general anesthesia. A multidisciplinary apaproach of brief inpatient rehabilitation and continuous blockade via an indwelling pain catheter may provide a safer, more cost-effective means of restoring function in children with advanced disease.


The complete mitochondrial genomes of the Leuciscus baicalensis and Rutilus rutilus: A detailed genomic comparison among closely related species of the Leuciscinae subfamily.
Cyprinidae is the largest family in the order of freshwater fish Cypriniformes. Increased subfamily members of Cyprinidae have been suggested to be re-classified for decades. In this study, we sequenced the mitochondrial genomes (mitogenomes) of Leuciscus baicalensis and Rutilus rutilus collected from northwest China and compared with other closely related species to determine their associated family or subfamily. We used Illumina NovaSeq to sequence the entire mitochondrial genomes of Leuciscus baicalensis and Rutilus rutilus and characterized the mitogenomes by the gene structure, gene order, and the secondary structures of the 22 tRNA genes. We compared mitogenome features of Leuciscinae with other subfamilies in Cyprinidae. We used the analytic Bayesian Information and Maximum Likelihood methods to determine phylogenetic trees of 13 PCGs. The mitogenomes of Leuciscus baicalensis and Rutilus rutilus were 16,607 bp and 16,606 bp, respectively. Organization and location of these genes were consistent with already studied Leuciscinae fishes. Synonymous codon usage was conservative in Leuciscinae as compared with other subfamilies in Cyprinidae. Phylogenetic analysis indicated that Leuciscinae was a monophyletic group, and genus Leuciscus was a paraphyletic group. Our approach, for the first time, of studying comparative mitochondrial genomics and phylogenetics together provided a supportive platform to the analysis of population genetics and phylogeny for Leuciscinae. Our results indicated a promising potential of comparative mitochondrial genomics in the manifestation of phylogenetic relationships between fishes, leading us to a suggestion that mitogenomes should be routinely considered in clarifying phylogenetics of family and subfamily members of fish.


Mutation at residue 376 of ALS confers tribenuron-methyl resistance in flixweed (Descurainia sophia) populations from Hebei Province, China.
The acetolactate synthase (ALS) inhibitor tribenuron has been used continuously for approximately twenty years as an herbicide in winter wheat fields in China. Flixweed (Descurainia sophia) has evolved resistance to tribenuron, due to multiple amino acid mutations at the 197th residue of ALS. In this study, the molecular basis of tribenuron resistance was investigated using two resistant populations, Xingtai (XT) and Shijiazhuang (SJ), and two susceptible populations, Cangzhou (CZ) and Handan (HD). Whole-plant tests and ALS activity assays showed that the two resistant populations were highly resistant to tribenuron. Targeted amplification of ALS genes from the four populations showed that there were two ALS genes in each population, and both of them were expressed in flixweed; the full coding lengths of the two ALS genes were 1998bp and 2004bp. Mutations related to tribenuron resistance in flixweed were located in only the 1998bp paralog. An ALS activity assay showed that the resistant population SJ displayed slight cross-resistance to florasulam, with a resistance factor of 4.81, but the resistant population XT did not have cross-resistance to florasulam. The resistant population XT was found to carry the previously reported mutation Pro197Ser, but the resistant population SJ carried a different mutation, Asp376Glu, known from other weeds but novel in flixweed. Our results demonstrated that multiple versions of ALS genes exist in flixweed and that mutations at multiple sites may result in ALS-inhibitor resistance in this weed.


[Acetylhydroxamic acid in the treatment of nephrolithiasis, caused by infection with urease forming microorganisms].
Acetohydroxam acid (500-1000 mg/d) inhibit the activity of the bacterial urease successfully due to reduction of ammonia excretion and urinary pH value in the patients. Acetohydroxam acid should be used in patients after operative treatment of urolithiasis due to infection with carbamidesplitting bacteria.


Philadelphia chromosome-positive acute myeloid leukemia with tetraploidy.
The patient was a 62-year-old man. His hematological data in April 2000 had shown no abnormalities, but he was referred to our hospital because of a fever and leukocytosis in June 2000. The peripheral blood showed 29.8 x 10(9)/L white blood cells, with 68.0% blasts. A bone marrow aspirate showed hypercellularity with a proliferation of large leukemic blasts. The leukemic cells were positive for CD13 (91%), CD33 (54.8%), CD34 (94.5%), and HLA-DR (97.9%). Some leukemic cells (15.6%) also expressed CD14. Cytogenetic analysis revealed 92,XXYY,t(9;22)(q34;q11)x2 in all 20 metaphase cells. Reverse transcriptase polymerase chain reaction analysis detected the minor BCR/ABL messenger RNA (mRNA) but failed to detect the major BCR/ABL mRNA. The patient achieved complete remission after induction chemotherapy, with no evidence of Philadelphia chromosome (Ph) or minor BCR/ABL mRNA. Ph-positive acute myeloid leukemia (Ph-AML) has rarely been reported. Herein, we report a case of Ph-AML with tetraploidy and review the previously reported Ph-AML cases.


Tetranuclear Lanthanide Complexes Containing a Hydrazone-type Ligand. Dysprosium [2 × 2] Gridlike Single-Molecule Magnet and Toroic.
A multidentate hydrazone-type ligand (Z,Z)-bis(1-(pyridin-2-yl)-1-amino-methylidene)oxalohydrazide (H2L) was utilized in the synthesis of three new isomorphous tetranuclear complexes of the general formula [Ln4(HL)4(H2L)2(NO3)4](NO3)4·4CH3OH (Ln = GdIII, 1, TbIII, 2, DyIII, 3) with the gridlike [2 × 2] topology. The analysis of the static magnetic data revealed weak anti-ferromagnetic interaction among lanthanide(III) atoms, whereas dynamic magnetic data led to the observation of the single-molecule magnet behavior in zero static magnetic field for the Dy4 compound 3 with Ueff = 42.6 K and τ0 = 1.50 × 10-5 s. The theoretical CASSCF calculations supported also the presence of the net toroidal magnetic moment, which classifies compound 3 also as a single-molecule toroic.


Experimental evaluation of the effect of raised pressure in a single compartment in the lower leg on neighbouring compartments using fresh above knee amputated legs-a study of interstitial pressures with two case reports.
Experimental evaluation of intracompartmental pressures in a fresh above knee amputated human leg. To determine what effect raised pressure in one compartment of the lower leg had upon its neighbour. There has been no previous reports of isolated compartment pathology, following low velocity trauma, causing a compartment syndrome in all four compartments of the lower leg. Immediately after leg amputation, the intracompartmental pressure in the deep posterior compartment was artificially raised to 100 mmHg with infused 0.9% sodium chloride solution. The resultant pressure changes in remaining compartments were recorded over 30 min. Five legs were evaluated. After 30 min, the mean maximum intracompartmental pressure increase found in the superficial posterior, anterior and peroneal compartments was 78.4 mmHg (range 65-94 mmHg), 25.2 mmHg (range 14-31 mmHg) and 24.8 mmHg (range 15-31 mmHg), respectively. This experimental data and case reports show that a compartment in which there is raised pressure may exert external pressure on a neighbouring compartment that can result in physiological changes to induce a compartment syndrome within that neighbour. The importance of assessing all compartments within a limb segment, even when associated with low velocity trauma, remains paramount.


Angiotensin binding sites in bovine and human retinal blood vessels.
Blood vessels isolated from bovine and human retinas have sites that specifically bind 3H-angiotensin II (3H-Ag II) with an apparent dissociation constant (Kd) of 14 nM and a capacity of binding (Bmax) of 0.82 pmol/g. The binding sites for 3H-Ag II appear to be influenced by guanine nucleotides (GTP) and cations (Mg2+ and Na+) in a way that resembles angiotensin II receptors in other tissues. The physiologic effect of blood-borne or locally-formed angiotensin II on retinal blood flow remains to be defined.


Management of pediatric foot deformities: an imaging review.
Abnormalities of foot alignment can be a cause of significant morbidity in children, and some require complex surgical intervention to improve functionality and decrease pain. Imaging plays a key role in management decisions. We address some of the most common surgical strategies for selected diagnoses including pes planus, congenital vertical talus, pes cavus, and clubfoot, with a focus on imaging findings.


The behavioral risk factor surveys: II. Design, methods, and estimates from combined state data.
Behavioral risk factor (BRF) telephone surveys were conducted by 28 states and the District of Columbia from April 1981 through October 1983 to obtain baseline prevalence estimates for risk factors associated with the leading causes of death among adults. A supplemental survey was conducted to cover the remaining states (except Hawaii) in order to provide individual states with national-level data for comparison purposes. The complex sampling designs and variable sampling rates among state surveys required the computation of sample weights before estimates on a national level could be made. Estimates from the combined individual surveys are similar to those obtained from more expensive in-person interviews. The BRF national prevalence estimate of chronic heavier drinking is 8.7 percent, equivalent to the 1979 National Institute on Alcoholism and Alcohol Abuse (NIAAA) estimate of 9 percent. The BRF estimate of 31.5 percent for current smokers compares closely with the 32.6 percent estimated by the 1980 Health Interview Survey. Despite recognized technical limitations, this type of telephone survey can be a practical and affordable source of information both for initially gathering prevalence data and for monitoring trends in the prevalence of behavioral risk factors of public health concern.


In vitro comparison of the physical and mechanical properties of an ormocer with an ormocer-based composite and a nanocomposite restorative material.
To compare an ormocer with a first generation ormocer-based composite and a nanocomposite in terms of surface roughness, surface hardness, and microleakage. An ormocer (Admira Fusion), a first generation ormocer-based composite (Admira) and a nanocomposite (Filtek Z350 XT) were prepared strictly in accordance with the manufacturer's instruction and recommendation to provide optimal material properties. Twelve disk samples of each material were evaluated to assess both surface roughness and surface hardness. For surface roughness, all samples were finished, polished, and Ra values measured with a profilometer. For surface hardness, samples were stored in an incubator, polished and a Vickers diamond indenter was used to record values. For microleakage, 36 standardized, Class V cavities were prepared and randomly divided into three groups. Restored teeth were thermally fatigued, immersed in 2% methylene blue solution for 48 h, sectioned, and scored for occlusal and gingival microleakage. Statistical significance was set at p < .05. The one-way analysis of variance identified no significant difference in terms of surface roughness between the three material groups (p > .05). A significantly higher surface hardness was identified for the nanocomposite compared to both the ormocer (p < .001) and ormocer-based composite (p < .001). Fisher's exact test identified no significant difference in terms of occlusal microleakage (p = .534) and gingival microleakage (p = .093) between the three material groups. No significant differences in terms of surface roughness or microleakage were noted. The nanocomposite was significantly harder than the ormocer materials.


High-performance permanent magnet array design by a fast genetic algorithm (GA)-based optimization for low-field portable MRI.
Lightweight and compact permanent magnet arrays (PMAs) are suitable for portable dedicated magnetic resonance imaging (MRI). It is worth exploring different PMA design possibilities and optimization methods with an adequate balance between weight, size, and performance, in addition to Halbach arrays and C-shaped/H-shaped magnets which are widely used. In this paper, the design and optimization of a sparse high-performance inward-outward ring-pair PMA consisting of magnet cuboids is presented for portable imaging of the brain. The design is lightweight (151kg) and compact (inner bore diameter: 270mm, outer diameter: 616mm, length: 480mm, 5-Gauss range: 1840×1840×2340mm3). The optimization framework is based on the genetic algorithm with a consideration of both field properties and simulated image quality. The resulting PMA design has an average field strength of 101.5 mT and a field pattern with a built-in linear readout gradient. Subtracting the best fit to the linear gradient target resulted in a residual deviation from the target field of 0.76mT and an average linear regression coefficient of 0.85 to the linear gradient. The required radiofrequency bandwidth is 6.9% within a field of view (FoV) with a diameter of 200mm and a length of 125mm. It has a magnetic field generation efficiency of 0.67mT/kg, which is high among the sparse PMAs that were designed for an FoV with a diameter of 200mm. The field can be used to supply gradients in one direction working with gradient coils in the other two directions, or can be rotated to encode signals for imaging with axial slice selection. The encoding capability of the designed PMA was examined through the simulated reconstructed images. The force experienced by each magnet in the design was calculated, and the feasibility of a physical implementation was confirmed. The design can offer an increased field strength, and thus, an increased signal-to-noise ratio. It has a longitudinal field direction that allows the application of technologies developed for solenoidal magnets. This proposed design can be a promising alternative to supplying the main and gradient fields in combination for dedicated portable MRI. Lastly, the design is resulted from a fast genetic algorithm-based optimization in which fast magnetic field calculation was applied and high design flexibility was feasible. Within optimization iterations, image quality metrics were used for the encoding field of a magnet configuration to guide the design of the magnet array.


Multidisciplinary effort in treating children with hepatoblastoma in China.
The purpose of this study is to report the first nationwide protocol (Wuhan Protocol) developed by Chinese Children's Cancer Group and the results of multidisciplinary effort in treating hepatoblastoma. In this study, we reported the final analysis, which includes 153 hepatoblastoma patients in 13 hospitals from January 2006 to December 2013. The 6-year overall survival and event-free survival rates were 83.3 ± 3.1% and 71.0 ± 3.7%, respectively, in this cohort. The univariate analysis revealed that female (P = 0.027), under 5 years of age (P = 0.039), complete surgical resection (P = 0.000), no metastases (P = 0.000), and delayed surgery following neoadjuvant chemotherapy (P = 0.000) had better prognosis. In multivariate analysis, male, 5 years of age or above, stage PRETEXT III or IV, and incomplete surgical resection were among the some adverse factors contributing to poor prognosis. The preliminary results from this study showed that patients who underwent treatment following Wuhan Protocol had similar OS and EFS rates compared to those in developed countries. However, the protocol remains to be further optimized in standardizing surgical resection (including liver transplantation), refining risk stratification and risk-based chemotherapy.


Tissue testosterone and dihydrotestosterone from bilateral testis biopsies in males with varicocele.
Nine males with varying degrees of subfertility with left varicocele underwent bilateral testicular biopsy for determination of testicular testosterone (T) and dihydrotestosterone (DHT) content. Testicular tissue T and DHT levels varied greatly, and there was no significant difference when the group T and DHT content of the left testis was compared with that of the right testis. When the respective mean preoperative sperm count was compared with the bilateral tissue T and DHT content, no consistent relationship was found.


The protein corona of circulating PEGylated liposomes.
Following systemic administration, liposomes are covered by a 'corona' of proteins, and preserving the surface functionality is challenging. Coating the liposome surface with polyethylene glycol (PEG) is the most widely used anti-opsonization strategy, but it cannot fully preclude protein adsorption. To date, protein binding has been studied following in vitro incubation to predict the fate of liposomes in vivo, while dynamic incubation mimicking in vivo conditions remains largely unexplored. The main aim of this investigation was to determine whether shear stress, produced by physiologically relevant dynamic flow, could influence the liposome-protein corona. The corona of circulating PEGylated liposome was thoroughly compared with that formed by incubation in vitro. Systematic comparison in terms of size, surface charge and quantitative composition was made by dynamic light scattering, microelectrophoresis and nano-liquid chromatography tandem mass spectrometry (nanoLC-MS/MS). Size of coronas formed under static vs. dynamic incubation did not appreciably differ from each other. On the other side, the corona of circulating liposomes was more negatively charged than its static counterpart. Of note, the variety of protein species in the corona formed in a dynamic flow was significantly wider. Collectively, these results demonstrated that the corona of circulating PEGylated liposomes can be considerably different from that formed in a static fluid. This seems to be a key factor to predict the biological activity of a liposomal formulation in a physiological environment.


Intracellular potassium activities of horizontal cells and extracellular potassium activity in isolated retinae of a cyprinid fish.
Extracellular and intracellular K+ activities of luminosity and biphasic-chromaticity type horizontal cells were measured in non-superfused roach retinae using double-barrelled K+-sensitive micro-electrodes. The extracellular K+ activity in dark-adapted retinae was 3.4 mM on average. The intracellular K+ activities of the two types of horizontal cell in the dark were very similar (57 and 54 mM, respectively), and corresponding values of the K+ equilibrium potential were about 35 mV more negative than respective resting potentials. During light-evoked hyperpolarizations, the intracellular K+ activity decreased, and at saturation, resting potentials matched corresponding K+ equilibrium potentials. The results are discussed in relation to sub-synaptic and non-synaptic membrane ionic mechanisms and further support the view that the non-synaptic membrane is selectively permeable to K+.


Sparing internal thoracic vessels in thoracoscopic or submuscular correction of pectus carinatum: A porcine model study.
External compression is used for pectus carinatum (PC) treatment, but many patients are noncompliant. Costal cartilage resection (CCR) has been described as an alternative, but these approaches sacrifice the internal thoracic arteries (ITA). We aim to assess the feasibility of CCR sparing ITA comparing thoracoscopic and subcutaneous endoscopic approaches. Twelve pigs were used as models for surgical PC correction and randomized for 2 groups: thoracoscopy (T) and subcutaneous (subpectoralis) endoscopy (SP). In both groups, CCR from 3rd 4th and 5th ribs was performed avoiding ITA damage. ITA preservation was confirmed by Doppler-ultrasound as well as postmortem injection of methylene blue. Four persons evaluated the procedures being difficult, using a 6-item modified validated scale. In both techniques, the procedure was accomplished in all animals sparing ITAs. CCR was faster in T than in SP (49±5 vs. 65±16minutes, p<0.05). T was classified as easier than SP (p<0.001) with a significantly higher score for all items, especially better image and tissue handling. Sparing the ITAs during CCR for correction of PC is feasible in a porcine model and might be a goal in humans. The thoracoscopic approach allows for a faster and easier procedure.


IL-6 in malignant pleural effusions and its augmentation by intrapleural instillation of IL-2.
The levels and activities of endogenous IL-6 in malignant pleural effusions due to lung cancer before and during daily intrapleural instillations of recombinant IL-2 were examined by enzyme immunoassay and bioassay using an IL-6-dependent murine hybridoma cell line MH60.BSF2. Before therapy, malignant pleural effusions contained various levels of IL-6. Daily intrapleural instillation of recombinant IL-2 for treatment of malignant pleurisy resulted in significant augmentation of the levels and activities of IL-6 in the pleural effusions. On fractionation of the pleural effusion by chromatography, one major peak of material with a mol. wt of 24 kD showed IL-6 activity. In contrast, no significant level of tumour necrosis factor-alpha or IL-1 beta was detectable in pleural effusions before or during local IL-2 therapy. These data suggest that IL-2 is an important regulatory factor of secondary IL-6 production.


Preclinical evaluation of BAY 1075553, a novel (18)F-labelled inhibitor of prostate-specific membrane antigen for PET imaging of prostate cancer.
Prostate-specific membrane antigen (PSMA) is a transmembrane protein overexpressed in prostate cancer and is therefore being explored as a biomarker for diagnosing and staging of the disease. Here we report preclinical data on BAY 1075553 (a 9:1 mixture of (2S,4S)- and (2R,4S)-2-[(18)F]fluoro-4-phosphonomethyl-pentanedioic acid), a novel (18)F-labelled small molecule inhibitor of PSMA enzymatic activity, which can be efficiently synthesized from a direct radiolabelling precursor. The (18)F-radiolabelled stereoisomers of 2-[(18)F]fluoro-4-(phosphonomethyl)-pentanedioic acid were synthesized from their respective isomerically pure precursors dimethyl 2-{[bis(benzyloxy)phosphoryl]methyl}-4-(tosyloxy)pentanedioate. In vivo positron emission tomography (PET) imaging and biodistribution studies were conducted in mice bearing LNCaP, 22Rv1 and PC-3 tumours. Pharmacokinetic parameters and dosimetry estimates were calculated based on biodistribution studies in rodents. For non-clinical safety assessment (safety pharmacology, toxicology) to support a single-dose human microdose study, off-target effects in vitro, effects on vital organ functions (cardiovascular in dogs, nervous system in rats), mutagenicity screens and an extended single-dose study in rats were conducted with the non-radioactive racemic analogue of BAY 1075553. BAY 1075553 showed high tumour accumulation specific to PSMA-positive tumour-bearing mice and was superior to other stereoisomers tested. Fast clearance of BAY 1075553 resulted overall in low background signals in other organs except for high uptake into kidney and bladder which was mainly caused by renal elimination of BAY 1075553. A modest uptake into bone was observed which decreased over time indicating organ-specific uptake as opposed to defluorination of BAY 1075553 in vivo. Biodistribution studies found highest organ doses for kidneys and the urinary bladder wall resulting in a projected effective dose (ED) in humans of 0.0219 mSv/MBq. Non-clinical safety studies did not show off-target activity, effects on vital organs function or dose-dependent adverse effects. BAY 1075553 was identified as a promising PET tracer for PSMA-positive prostate tumours in preclinical studies. BAY 1075553 can be produced using a robust, direct radiosynthesis procedure. Pharmacokinetic, toxicology and safety pharmacology studies support the application of BAY 1075553 in a first-in-man microdose study with single i.v. administration.


Prediction of treatment outcome in neovascular age-related macular degeneration using a novel convolutional neural network.
While prognosis and risk of progression are crucial in developing precise therapeutic strategy in neovascular age-related macular degeneration (nAMD), limited predictive tools are available. We proposed a novel deep convolutional neural network that enables feature extraction through image and non-image data integration to seize imperative information and achieve highly accurate outcome prediction. The Heterogeneous Data Fusion Net (HDF-Net) was designed to predict visual acuity (VA) outcome (improvement ≥ 2 line or not) at 12th months after anti-VEGF treatment. A set of pre-treatment optical coherence tomography (OCT) image and non-image demographic features were employed as input data and the corresponding 12th-month post-treatment VA as the target data to train, validate, and test the HDF-Net. This newly designed HDF-Net demonstrated an AUC of 0.989 (95% CI 0.970-0.999), accuracy of 0.936 [95% confidence interval (CI) 0.889-0.964], sensitivity of 0.933 (95% CI 0.841-0.974), and specificity of 0.938 (95% CI 0.877-0.969). By simulating the clinical decision process with mixed pre-treatment information from raw OCT images and numeric data, HDF-Net demonstrated promising performance in predicting individualized treatment outcome. The results highlight the potential of deep learning to simultaneously process a broad range of clinical data to weigh and leverage the complete information of the patient. This novel approach is an important step toward real-world personalized therapeutic strategy for typical nAMD.


Scientific research ability of specialist nurses in Guangxi Zhuang Autonomous Region, China: A cross-sectional study.
This study investigated the scientific research ability of Chinese specialist nurses (SNs) in the Guangxi Zhuang Autonomous Region and its influencing factors. A cross-sectional design. A total of 652 SNs in the Guangxi Zhuang Autonomous Region were investigated from March to October 2021. The nursing scientific research ability level was measured using the Nursing Research Competence of Nurses Self-evaluation Scale. Descriptive statistics, univariate analysis and ordinal logistic regression analysis were used to evaluate factors affecting the scientific research ability of SNs. The median score of scientific research ability of SNs was 31 (interquartile range: 19-41). Approximately 74.8% of clinical speciality nurses had low scientific research ability. Educational background, working hospital level, being the first author of a published paper and successful application for scientific research projects were identified as factors influencing scientific research ability score.


Evaluation of a hospital-wide vancomycin-dosing nomogram in patients with continuous-flow left ventricular assist devices.
Hemodynamic derangements due to heart failure are associated with alterations in pharmacokinetics. Although use of mechanical circulatory support mitigates such derangements, little evidence is available regarding pharmacokinetics in patients with LVADs. A previous pharmacokinetic analysis of vancomycin among patients with LVADs observed a reduced volume of distribution and clearance compared with estimates based on population kinetics. A total of 28 adult patients with LVADs hospitalized between January 2014 and May 2018 who received vancomycin through a pharmacist dosing consult were included. Internal medicine patients without heart failure receiving vancomycin were enrolled in a 2:1 fashion to make a control group. Exclusion criteria were unstable renal function, ESRD, acute decompensation, cardiac surgery within the preceding 5 days, or weight >110 kg. No difference was observed in the proportion achieving goal trough (64% of LVAD patients vs 71% control patients, p = 0.50). However, mean trough was significantly higher among LVAD patients (23.4 mg/L vs 17.7 mg/L, p = 0.017). Furthermore, there was a significant difference in the distribution of trough levels (p = 0.025) with LVAD patients being more likely to attain levels >25 mg/L (32% vs 14%) and less likely to have troughs <10 mg/L (4% vs 14%). A numerically greater number of LVAD patients experienced nephrotoxicity but this did not reach statistical significance (32% vs 18%, p = 0.14). The use of vancomycin in LVAD patients may result in higher trough levels when compared to internal medicine patients. Increased monitoring or conservative dosing may be warranted to improve safety and efficacy.


[Seasonal dynamics of adrenal mineralocorticoid function in rats].
Seasonal peculiarities of adrenal mineralocorticoid function and some aspects of its regulation have been studied in experiments on male Wistar rats. It has been found that changes in aldosteronemia and aldosteronurea were maximum in spring and minimum in summer--autumn period. The highest indices of aldosterone metabolic clearance from plasma were observed in winter with the following progressing decrease and a small increase in autumn. The diagram of melatonin content in the epiphysis of experimental rats was the same. Hypokinesia attenuated aldosteronurea during all the investigation periods, preserving the character of aldosterone secretion year curve. PRA level changed irrespective of aldosterone levels in plasma and urea. It has been concluded that a certain stability of mineralocorticoid adrenal function seasonal rhythms has different regulating effects.


Nephron number determines susceptibility to renal mass reduction-induced CKD in Lewis and Fisher 344 rats: implications for development of experimentally induced chronic allograft nephropathy.
The Fisher 344 (F344) rat kidney transplanted to a Lewis rat recipient is a common model of chronic renal allograft nephropathy (CAN); however, CAN does not develop when the Lewis kidney is grafted into a F344 recipient. In this study we investigated whether a difference in nephron number/glomerular volume exists between the strains that could contribute to a greater susceptibility to development of kidney disease in the F344. Separate animals, male F344 and Lewis rats, were subjected to either sham surgery or right uni-nephrectomy and infarction of 2/3 of the left kidney, to produce a 5/6 ablation/infarction injury (5/6 A/I). Serial urinary protein excretions were measured, a terminal 24-h creatinine clearance was obtained and rats were killed 11 weeks after surgery and kidneys were harvested for pathology. Glomerular volumes were measured in the sham controls of each strain. Glomerular number was counted in separate, normal rats of each strain. The normal F344 had approximately 30% fewer glomeruli than Lewis rats that were larger in volume. The sham F344 had similar creatinine clearance and glomerular structure to the Lewis shams, although BP and urine protein excretion were higher. After 5/6 A/I the F344 developed more severe proteinuria and structural kidney damage. When factored for kidney weight, the F344 rats exhibited a greater compensatory hyperfiltration in response to 5/6 A/I, compared to Lewis. The F344 strain is more vulnerable to development of progressive kidney damage due to 5/6 A/I, compared to the Lewis. This is likely due to the lower nephron number/greater glomerular volume of the F344 that may also account for the greater susceptibility to CAN exhibited by this strain.


Crystal structure of bis-[4-(all-yloxy)-N'-(but-2-en-1-yl-idene)benzohydrazidato]nickel(II).
In the title complex, [Ni(C14H15N2O2)2], the nickel(II) atom exhibits a square-planar coordination geometry, being coordinated by two negatively charged N,O chelating ligands in a trans configuration, with the metal located on a crystallographic center of symmetry. The X-ray structural characterization showed the complex to be disordered over two orientations with refined occupancies of 0.898 (2) and 0.102 (2). The whole mol-ecule is close to planar, the five- and six-membered rings subtending a dihedral angle of 7.5 (2)°. The crystal packing is supported by C-H⋯π and C-H⋯O inter-actions that form a di-periodic layered network.


Selective photolabeling of proteins using photoactivatable GFP.
Today's cell biologists rely on an assortment of advances in microscopy methods to study the inner workings of cells and tissues. Among these advances are fluorescent proteins which can be used to tag specifically and, in many cases, non-invasively proteins of interest within a living cell. Introduction of DNA encoding the fluorescently tagged protein of interest into a cell readily allows the visualization of the protein's localization and time-lapse imaging allows the movement of the structure or organelle to which the protein is localized to be observed. To monitor the movement of the protein within the population, researchers generally have to highlight a pool of molecules by perturbing the steady-state fluorescence. This perturbation has traditionally been performed by photobleaching the molecules within a selected region of the cell and monitoring the recovery of molecules into this region or the loss of molecules within other regions. Fluorescent proteins are now available, which allow a pool of molecules to be highlighted directly by photoactivation. Here, we discuss the technical aspects for using one of these recently developed photoactivatable fluorescent proteins, PA-GFP.


Kinesin-14 HSET and KlpA are non-processive microtubule motors with load-dependent power strokes.
Accurate chromosome segregation during cell division relies on coordinated actions of microtubule (MT)-based motor proteins in the mitotic spindle. Kinesin-14 motors play vital roles in spindle assembly and maintenance by crosslinking antiparallel MTs at the spindle midzone and anchoring spindle MTs' minus ends at the poles. We investigate the force generation and motility of the Kinesin-14 motors HSET and KlpA, revealing that both motors function as non-processive motors under load, producing single power strokes per MT encounter. Each homodimeric motor generates forces of ∼0.5 pN, but when assembled in teams, they cooperate to generate forces of 1 pN or more. Importantly, cooperative activity among multiple motors leads to increased MT-sliding velocities. Our findings deepen our understanding of the structure-function relationship of Kinesin-14 motors and underscore the significance of cooperative behavior in their cellular functions.


Corticosteroid therapy does not prevent nephritis in Henoch-Schönlein purpura.
Nephritis occurs in 20%-50% of children with Henoch-Schönlein purpura (HSP), and the onset of renal involvement may be delayed for weeks or months in a substantial proportion of patients. The present study was performed to determine whether corticosteroid therapy was effective in preventing delayed nephritis in children with HSP. The medical records of 69 children with HSP were reviewed. Nineteen patients had acute nephritis occurring from 1-12 days after the onset of other signs and symptoms. The remaining 50 patients had no evidence of acute renal involvement. Of these 50 patients, 20 were treated during the acute phase of the illness with corticosteroids, while 30 never received corticosteroid therapy. Delayed nephritis (> 3 weeks following an initial normal urinalysis) occurred in 4 of 20 (20%) patients who received prior corticosteroid treatment, and in 6 of 30 (20%) patients who were not treated. These results indicate that early corticosteroid therapy does not prevent delayed nephritis in children with HSP.


Uterine papillary serous carcinoma: state of the state.
Uterine papillary serous carcinoma (UPSC) is an aggressive form of endometrial cancer that is likely to present with deep myometrial invasion and lymph vascular involvement. By the time most affected women are diagnosed, the UPSC has spread outside the uterus. Because many reports include patients who are not completely staged, the risk of recurrence in stage I patients has likely been overestimated. Recently, several large series of well-staged patients have demonstrated that survival in stage I patients is similar to that of poorly differentiated endometrioid tumors. Because of the high risk of extrauterine spread, all patients with UPSC should have an extended surgical staging procedure, including lymphadenectomy and omentectomy. Chemotherapy with or without local or regional radiation is probably the most effective adjuvant therapy in both early and advanced disease. Because patients with stage I UPSC are still at significant risk of recurrence, adjuvant therapy is often recommended for all patients. It has been difficult to conduct prospective randomized trials for patients with UPSC because of the rare nature of these cancers.


Haemophilus aphrophilus as a cause of chronic suppurative pulmonary infection and intra-abdominal abscesses.
A chronic Haemophilus aphrophilus pulmonary infection associated with the formation of intra-abdominal abscesses in a previously healthy 38-year-old man is described. Other reports have related the isolation of H. aphrophilus to underlying malignant disease or, when the cause of endocarditis, to pre-existing valvular disease. The underlying condition, if any, in this case remains unclear.