Symptomatic contralateral subdural hygromas after decompressive craniectomy: plausible causes and management protocols.
Contralateral subdural hygromas are occasionally observed after decompressive craniectomies (DCs). Some of these hygromas are symptomatic, and the etiology and management of these symptomatic contralateral subdural collections (CLDCs) present surgical challenges. The authors share their experience with managing symptomatic CLSDCs after a DC. During a 10-month period, 306 patients underwent a DC. Of these patients, 266 had a head injury, 25 a middle cerebral artery infarction (that is, a thrombotic stroke), and 15 an infarction due to a vasospasm (resulting from an aneurysmal subarachnoid hemorrhage [SAH]). Seventeen patients (15 with a head injury and 2 with an SAH) developed a CLSDC, and 7 of these patients showed overt symptoms of the fluid collection. These patients were treated with a trial intervention consisting of bur hole drainage followed by cranioplasty. If required, a ventriculo- or thecoperitoneal shunt was inserted at a later time. Seven patients developed a symptomatic CLSDC after a DC, 6 of whom had a head injury and 1 had an SAH. The average length of time between the DC and CLSDC formation was 24 days. Fluid drainage via a bur hole was attempted in the first 5 patients. However, symptoms in these patients improved only temporarily. All 7 patients (including the 5 in whom the bur hole drainage had failed and 2 directly after the DC) underwent a cranioplasty, and the CLSDC resolved in all of these patients. The average time it took for the CLSDC to resolve after the cranioplasty was 34 days. Three patients developed hydrocephalus after the cranioplasty, requiring a diversion procedure, and 1 patient contracted meningitis and died. Arachnoid tears and blockage of arachnoid villi appear to be the underlying causes of a CLSDC. The absence of sufficient fluid pressure required for CSF absorption after a DC further aggravates such fluid collections. Underlying hydrocephalus may appear as subdural collections in some patients after the DC. Bur hole drainage appears to be only a temporary measure and leads to recurrence of a CLSDC. Therefore, cranioplasty is the definitive treatment for such collections and, if performed early, may even avert CLSDC formation. A temporary ventriculostomy or an external lumbar drainage may be added to aid the cranioplasty and may be removed postoperatively. Ventriculoperitoneal or thecoperitoneal shunting may be required for patients in whom a hydrocephalus manifests after cranioplasty and underlies the CLSDC.


Identifying differentially coexpressed module during HIV disease progression: A multiobjective approach.
Microarray analysis based on gene coexpression is widely used to investigate the coregulation pattern of a group (or cluster) of genes in a specific phenotype condition. Recent approaches go one step beyond and look for differential coexpression pattern, wherein there exists a significant difference in coexpression pattern between two phenotype conditions. These changes of coexpression patterns generally arise due to significant change in regulatory mechanism across different conditions governed by natural progression of diseases. Here we develop a novel multiobjective framework DiffCoMO, to identify differentially coexpressed modules that capture altered coexpression in gene modules across different stages of HIV-1 progression. The objectives are built to emphasize the distance between coexpression pattern of two phenotype stages. The proposed method is assessed by comparing with some state-of-the-art techniques. We show that DiffCoMO outperforms the state-of-the-art for detecting differential coexpressed modules. Moreover, we have compared the performance of all the methods using simulated data. The biological significance of the discovered modules is also investigated using GO and pathway enrichment analysis. Additionally, miRNA enrichment analysis is carried out to identify TF to miRNA and miRNA to TF connections. The gene modules discovered by DiffCoMO manifest regulation by miRNA-28, miRNA-29 and miRNA-125 families.


Recent Advances in Supramolecular Gels and Catalysis.
Over the past two decades, supramolecular gels have attracted significant attention from scientists in diverse research fields and have been extensively developed. This review mainly focuses on the significant achievements in supramolecular gels and catalysis. First, by incorporating diverse catalytic sites and active organic functional groups into gelator molecules, supramolecular gels have been considered as a novel matrix for catalysis. In addition, these rationally designed supramolecular gels also provide a variety of templates to access metal nanocomposites, which may function as catalysts and exhibit high activity in diverse catalytic transformations. Finally, as a new kind of biomaterial, supramolecular gels formed in situ by self-assembly triggered by catalytic transformations are also covered herein.


Small cell carcinoma of the ovary hypercalcemic type (SCCOHT): A rare case after in vitro fertilization (IVF).
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a very rare and lethal tumor, mostly affecting young women, with aggressive clinical course. It has a worse prognosis in younger women and most of them died within two years of diagnosis. We are reporting a unique case of SCCOHT in a 35 years old, nulliparous lady with primary infertility in which symptomatic hypercalcemia was a presenting feature of her cancer. She was completely healthy before third cycle of IVF. Within two months of her third IVF cycle, she developed SCCOHT with a very rapid and aggressive course of disease and fatal outcome. Patient died within one month of her first symptom presentation (3 months after IVF cycle).


Progression-free survival as a surrogate endpoint for overall survival in modern ovarian cancer trials: a meta-analysis.
Progression-free survival (PFS) has been adopted as the primary endpoint in many randomized controlled trials, and can be determined much earlier than overall survival (OS). We investigated whether PFS is a good surrogate endpoint for OS in trials of first-line treatment for epithelial ovarian cancer (EOC), and whether this relationship has changed with the introduction of new treatment types. In a meta-analysis, we identified summary data [hazard ratio (HR) and median time] from published randomized controlled trials. Linear regression was used to assess the association between treatment effects on PFS and OS overall, and for subgroups defined by treatment type, postprogression survival (PPS) and established prognostic factors. Correlation between HRs for PFS and OS, in 26 trials with 30 treatment comparisons comprising 24,870 patients, was modest (r2 = 0.52, weighted by trial sample size). The correlation diminished with recency: preplatinum/paclitaxel era, r2= 0.66; platinum/paclitaxel, r2= 0.44; triplet combinations, r2= 0.22; biologicals, r2= 0.30. The median PPS increased over time for the experimental (Ptrend = 0.03) and control arms (Ptrend = 0.003). The difference in median PPS between treatment arms strongly correlated with the difference in median OS (r2 = 0.83). In trials where the control therapy had median PPS of less than 18 months, correlation between PFS and OS was stronger (r2 = 0.64) than where the median PPS was longer (r2 = 0.48). In EOC, correlation in the relative treatment effect between PFS and OS in first-line platinum-based chemotherapy randomized controlled trials is moderate and has weakened with increasing availability of effective salvage therapies.


The diagnostic utility of procalcitonin, interleukin-6 and interleukin-8, and hyaluronic acid in the Norwegian consensus definition for early-onset neonatal sepsis (EONS).
A key challenge in identifying serious bacterial infection in new born infants is the nonspecific clinical presentation of early-onset neonatal sepsis (EONS). Routinely used C-reactive protein, white blood cell count, and platelets are nonspecific. We assessed the diagnostic utility of single biomarkers or combinations of procalcitonin (PCT), interleukin (IL)-6, IL-8, and hyaluronic acid (HA) in newborn infant with EONS, and in human umbilical cord blood (HUCB) from deliveries with chorioamnionitis. Blood was collected from term infants with strictly defined EONS (group 1, n=15), healthy term infants (group 2, n=15), and the umbilical vein from pregnancies with suspected chorioamnionitis (group 3, n=8), and from healthy pregnancies with no signs of infection (group 4, n=15). Neonatal plasma PCT and IL-8 showed good predictive value (90% and 83%) for EONS, and the combination of IL-6 or HA with PCT increased the predictability to 87% and 90%, respectively. PCT, IL-6, IL-8, and HA were 8.4-, 4.5-, 3.6-, and 1.9-fold higher when compared with plasma levels in noninfected neonates. PCT, IL-6, and IL-8 in HUCB predicted chorioamnionitis and fever in the delivering mother (89%, 83%, and 72%, respectively). HA was a poor predictor (59%), but its predictability increased in combination with PCT, IL-8, or IL-6. In HUCB from chorioamnionitic deliveries, IL-6, IL-8, and PCT were 23-, 14-, and 2.4-fold higher, respectively, when compared with HUCB from healthy deliveries. There was no correlation between C-reactive protein, white blood cell, and platelet count with PCT, IL-6, IL-8, or HA. In neonates that fulfilled the Norwegian consensus definition of neonatal sepsis, PCT, IL-6, and IL-8, but not HA, have the potential to improve our management of neonates at risk. Except for PCT and IL-8, both with a predictability of >80% in neonatal plasma, combinations of biomarkers increased the predictability for EONS and chorioamnionitis.


Forecasting and meta-features estimation of wastewater and climate change impacts in coastal region using manifold learning.
South Asia's coastlines are the most densely inhabited and economically active ecosystems have already begun to shift due to climate change. Over the past century, climate change has contributed to a gradual and considerable rise in sea level, which has eroded shorelines and increased storm-related coastal flooding. The differences in estuary water quality over time, both seasonally and annually, have been efficiently controlled by changes in stream flow. Assessment requires digitized analytical platforms to lower the risk of catastrophes associated with climate change in coastal towns. To predict future changes in an area's vulnerability and waste planning decisions, a prospective investigation requires qualitative and quantitative scenarios. The paper concentrates on the development of a forecasting platform to evaluate the climate change and waste water impacts on the south coastal region of India. Due to the enhancement of Digitization, a multi-model ensemble combined with manifold learning is implemented on the multi-case models influencing the uncertainty probability rate of 23% and can be ignored with desired precaution on the coastal environmental. Because Manifold Learning Analysis results cannot be utilized directly in wastewater management studies because of their inherent biases, a statistical bias correction and meta-feature estimation have been implemented. Within the climate-hydrology modeling chain, the results demonstrate a wide range of expected changes in water resources in some places. Experimental statistics reveal that the forecasted rate of 91.45% will be the better choice to reduce the uncertainty of climatic change and wastewater management.


A Novel Surgical Approach to Coracoid-based Eosinophilic Granuloma and the Technical Trick.
The coracoid base is a very rare location for tumors. It is difficult to diagnose and approach, but easy to dismiss. In this case, the tumor (eosinophilic granuloma of the scapula) was located at the base of the coracoid, and the posterior cortex was eroded by the tumor. Accessing this lesion through the deltopectoral approach with coracoid osteotomy without penetrating the supposed tumor extending posterior soft tissue will be discussed. This approach gives a wider and safer access to the surgeon than the posterior approach. This report presents a customized solution with the deltopectoral approach, and the chevron-type osteotomy to access the coracoid base and tension band wiring to fix the osteotomy side.


Direct percutaneous puncture versus transarterial embolization for head and neck paragangliomas: A systematic review and meta-analysis.
Embolization of head and neck paragangliomas (HNPs) is a well-established treatment strategy and adjunctive therapy. However, the optimal mode of intervention, whether by direct percutaneous puncture (DP) or via transarterial embolization (TAE), remains unclear. The aim of this study was to complete a systematic literature review and meta-analysis to compare the safety and efficacy of DP versus TAE for HNP embolization. The Cochrane Library and MEDLINE databases were used to identify studies describing the clinical outcomes of either DP or TAE for HNP embolization. Outcome measures included: complete angiographic devascularization, major complications, and minor complications. Pooled rates were calculated for each variable which were then compared with meta-regression using a random effects model. Thirty-one retrospective studies met inclusion criteria, detailing 394 patients with 411 HNPs. Overall, DP was associated with a higher rate of complete devascularization (91.5%, 95% confidence interval [CI]: 85.6% to 97.4%; I2 = 0%) when compared to TAE technique (40.1%, CI: 27.2% to 58.9%; I2 = 93%). However, there was no difference regarding major complication rates between DP (6%, CI:1.3% to 10.8%; I2 = 0%) and TAE for HNP embolization (3.3%, CI: 1.4% to 5.3%; I2 = 0%) (p = 0.370), nor in minor complications between the techniques (p = 0.211). Subgroup analysis of TAE embolic agents revealed that particle embolics were associated with a significantly lower rate of major complications (2.5%; 0.4% to 4.6%; I2 = 0%) when compared to liquid embolics (10.6%, CI:4% to 17.3%; I2 = 48%; p = 0.022). A DP approach for HNP embolization results in a higher rate of complete devascularization and with a similar complication profile when compared to TAE. These findings also suggest that particle embolics are associated with fewer major complications compared to liquid embolics when TAE is utilized.


Managing behavioral health care: an employer's perspective.
Employee life cycle events and behavioral health disorders impact productivity and well-being. Employers use wellness initiatives and employee assistance or work-family programs to help manage those factors that can distract employees from performing optimally. Employer-sponsored health benefits are designed to protect employees from the catastrophic costs of illness. However, today's plan designers struggle with employee and employer affordability that does not compromise quality or effectiveness. In 1990, Digital Equipment Corporation, Maynard, Mass., shifted its strategy from an indemnity model to a managed care model that uses health maintenance organizations. Comprehensive standards are used to ensure the delivery of quality behavioral health care that is cost effective, is delivered at the clinically appropriate levels, and uses a broad continuum of treatment approaches with measurable outcomes.


Naming vs. non-naming treatment in aphasia in a group setting-A randomized controlled trial.
Anomia affects numerous persons with aphasia. Treatment effects of anomia group therapy have been reported, but the evidence is not comprehensive. This study aimed to explore treatment effects of a naming treatment compared with a non-naming treatment delivered in a group setting. In a randomized controlled trial, 17 participants with chronic poststroke aphasia underwent group therapy, 2 hours a session, 3 times per week, for a total of 20 hours. The treatment given in the naming group was modified semantic feature analysis (SFA). Treatment content in the non-naming group comprised auditory comprehension, copying text, and reading. The primary outcome measure was accuracy in confrontation naming of participant-selected trained nouns and verbs. Generalization effects were evaluated in single-word naming, connected speech, and everyday communication. Participants in both groups significantly improved their naming of trained items. There were no differences between the groups. The treatment effect did not remain at follow-up 10 weeks after therapy. No other statistically significant changes occurred in either group. Group intervention can improve naming ability in individuals with chronic aphasia. However, similar treatment effects can be achieved using a non-naming treatment as using a naming treatment, such as modified SFA. Further research is warranted to identify the most important elements of anomia group therapy.


Marked suppression of tumor growth by FTY720 in a rat liver tumor model: the significance of down-regulation of cell survival Akt pathway.
We aim to investigate the anticancer effect of a novel immunomodulator FTY720 on a rat orthotopic liver tumor model. A buffalo rat orthotopic liver tumor model was established by injection of a buffalo hepatoma cell line MH7777 into the right portal vein. FTY720 was administered by intraperitoneal injection starting at 10 days after tumor cell injection at a dosage of 5 mg/kg/day. FTY720 markedly suppressed tumor growth and inhibited tumor progression by selective induction of apoptosis of tumor cells via down-regulation of phospho-Akt(ser473) and up-regulation of cleaved caspase-3, together with decrease of focal adhesion kinase. Moreover, the proliferation index of tumor cells was significantly reduced to 15.92+/-5.03% by FTY720 compared with that of 42.92+/-4.47% in the control group (p<0.001). In addition, we confirmed that FTY720 caused no effect on infiltrated lymphocyte in tumor tissue. We conclude that FTY720 is an effective anticancer agent for liver tumor in a rat model without affecting the immune system of the host.


[Analysis of prognosis and associated factors in multiple recurrent epithelial ovarian cancer with three times or more cytoreductive surgeries].
Objective: To explore the prognosis of epithelial ovarian cancer patients with multiple recurrences (≥2 times) who underwent three times or more cytoreductive surgeries, and to analyze the factors associated with prognosis. Methods: The clinicopathological data and follow-up data of 23 patients with ovarian cancer admitted to the Obstetrics and Gynecology Hospital of Fudan University from January 1, 2015 to January 30, 2022 with three times or more cytoreductive surgeries were collected. The degree of surgical resection, site of recurrence and metastasis, postoperative complications, and prognosis were retrospectively analyzed. The univariate Cox proportional hazards model was performed to identify the variables associated with survival. Results: (1) The median age of 23 patients with multiple recurrent ovarian cancer was 48 years old (44-55 years). Among them, 18 cases underwent tertiary cytoreductive surgery (TCS), 2 cases underwent quaternary cytoreductive surgery, 2 cases underwent quinary cytoreductive surgery, and 1 case underwent senary cytoreductive surgery. Among the 23 patients with multiple recurrent ovarian cancer, 21 cases (91%, 21/23) had serous carcinoma, 16 cases (70%, 16/23) had advanced stage (stage Ⅲ-Ⅳ), and 19 cases (83%, 19/23) had high differentiation. (2) Based on the premise that satisfactory cytoreduction was achieved by primary debulking surgery (PDS) and no visible residual disease (R0) was achieved by secondary cytoreductive surgery (SCS), the maximum diameter of the recurrent tumors was up to 10.0 cm and 62% (20/32) of patients with multiple metastatic sites. The R0 rate for three times or more cytoreductive surgeries (32 times in total) reached 88% (28/32), with a postoperative complication rate of 47% (15/32), and only 3% (1/32) for grade Ⅲ or above. During a median follow-up time of 31.1 months (20.6-43.9 months) after TCS, 20 patients (87%, 20/23) recurred after TCS, and 8 patients (35%, 8/23) eventually died of ovarian cancer. Among them, the three-year postoperative survival rate of 22 patients with R0 was 57.6%, and the patient with residual lesions ≥1 cm died at 9.2 months after TCS. (3) In univariate analysis, ages, the time interval between PDS and SCS >32 months, the interval between SCS and TCS >16 months, and no metastatic peritoneal carcinoma were associated with longer progression free survival after TCS (all P<0.05); while treatment-free interval (TFI) >10 months after SCS, the interval between SCS and TCS >16 months, no ascites and platinum-sensitive status were associated with disease-specific survival after TCS (all P<0.05). Conclusions: It is feasible to perform three times or more cytoreductive surgeries in patients with multiple recurrent ovarian cancer who are expected to achieve R0 and have manageable complications. However, the pros and cons of surgery need to be carefully evaluated for the patients whose ascites are massive and whose previous cytoreduction does not achieve R0. A prolonged TFI and previously longer surgical interval might get potential survival benefits.


Gliadin matrices for microencapsulation processes by simple coacervation method.
The aim of this study was to use a vegetal protein (gliadin) as a wall-forming component to produce microcapsules. The microencapsulation technique employed was the simple coacervation method and the encapsulated product was a non-food oil, hexadecane. Hexadecane was emulsified by a gliadin solution and the coacervation phenomena induced by adding a salt-solution in the continuous phase of the emulsion containing gliadin. The study of the coacervation conditions has shown that the richer in protein the continuous phase, the smaller the quantity of salt required. The main problem of the microencapsulation process by salting-out was to control the capsule size and the agglomeration of the capsules. This study succeeded in preventing the agglomeration phenomenon by adjusting the kinetics of the salt addition. When the feed rate of salt solution was very slow, this aggregation was considerably decreased. The suitable quantity of cross-linker (glutaraldehyde) to harden the microcapsules was determined by an electrophoresis method. The effect of different process parameters (gliadin concentration, quantity and addition kinetics of the coacervation agent, cross-linker concentration) was studied with regard to the final microcapsule characteristics (shape, size, composition, and mechanical resistance evaluated by a centrifugation test).


Hydrogen-bonded networks in 5-chloropyridin-2-amine-fumaric acid (2/1) and 2-aminopyridinium DL-malate.
Crystals of 5-chloropyridin-2-amine-(2E)-but-2-enedioate (2/1), 2C(5)H(5)ClN(2).C(4)H(4)O(4), (I), and 2-aminopyridinium DL-3-carboxy-2-hydroxypropanoate, C(5)H(7)N(2)(+).C(4)H(5)O(5)(-), (II), are built from the neutral 5-chloropyridin-2-amine molecule and fumaric acid in the case of (I) and from ring-N-protonated 2-aminopyridinium cations and malate anions in (II). The fumaric acid molecule lies on an inversion centre. In (I), the neutral 5-chloropyridin-2-amine and fumaric acid molecules interact via hydrogen bonds, forming two-dimensional layers parallel to the (100) plane, whereas in (II), oppositely charged units interact via ionic and hydrogen bonds, forming a three-dimensional network.


Behavioral neuroendocrinology and treatment of anorexia nervosa.
Outcome in anorexia nervosa remains poor and a new way of looking at this condition is therefore needed. To this aim, we review the effects of food restriction and starvation in humans. It is suggested that body weight remains stable and relatively low when the access to food requires a considerable amount of physical activity. In this condition, the human homeostatic phenotype, body fat content is also low and as a consequence, the synthesis and release of brain neurotransmitters are modified. As an example, the role of neuropeptide Y is analyzed in rat models of this state. It is suggested that the normal behavioral role of neuropeptide Y is to facilitate the search for food and switch attention from sexual stimuli to food. Descriptive neuroendocrine studies on patients with anorexia nervosa have not contributed to the management of the patients and the few studies in which hormones have been administered have, at best, reversed an endocrine consequence secondary to starvation. In a modified framework for understanding the etiology and treatment of anorexia nervosa it is suggested that the condition emerges because neural mechanisms of reward and attention are engaged. The neural neuropeptide Y receptor system may be involved in the maintenance of the behavior of eating disorder patients because the localization of these receptors overlaps with the neural systems engaged in cue-conditioned eating in limbic and cortical areas. The eating behavior of patients with anorexia nervosa, and other eating disorders as well, is viewed as a cause of the psychological changes of the patients. Patients are trained to re-learn normal eating habits using external support and as they do, their symptoms, including the psychological symptoms, dissolve.


Distribution of thrombomodulin in patients with focal and segmental glomerulosclerosis (FSGS).
Thrombomodulin (TM), an endothelial cell surface glycoprotein, is a regulatory factor in the intravascular anticoagulant system. Furthermore, its plasma level is believed to reflect injury to the endothelial cell. In searching for changes in intraglomerular coagulation and endothelial cell injury during the clinical course of 14 patients with focal and segmental glomerulosclerosis (FSGS), we evaluated the distribution of thrombomodulin (TM) in the kidney by immunohistochemical methods. In the nephrotic stage, intraglomerular staining for TM was weak and segmental and occurred in 6 out of 9 patients (67%), but the incidence of TM expression was not different significantly from that in the normal kidney. Sclerotic lesion was negative for TM. In all patients with incomplete remission and with complete remission, strong and diffuse staining was seen in intra- and extraglomerular endothelial cells. Moreover, TM was scattered in sclerotic lesions. The present study suggest that the over-expression of TM in remission may be linked to recovery from endothelial cell damage and that TM may be closely involved in the repair of FSGS.


Wettability and pre-osteoblastic behavior evaluations of a dense bovine hydroxyapatite ceramics.
In this study, the wettability, cell viability, and roughness of an experimental dense bovine hydroxyapatite [Ca10(PO4)6(OH)2] ceramic block were evaluated so that, in the future, it could be used as a base material for dental implants. The results to commercial zirconia and a commercially pure titanium (Ti) alloy were compared. The surface roughness and contact angles were measured. An in vitro evaluation was conducted by means of tests in which pre-osteoblastic MC3T3-E1 cells were placed in indirect and direct contact with these materials. For cell viability, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and crystal violet test were conducted. A qualitative analysis was conducted using variable pressure scanning electron microscopy (SEM). No statistically significant differences were observed in wettability and roughness tests among the groups. In both the MTT assay and crystal violet test, all groups demonstrated satisfactory results without cytotoxicity. SEM showed cell adhesion and cell proliferation results on the material surfaces after 24 h and 48 h. In conclusion, this dense Ca10 (PO4)6(OH)2 ceramic can be considered as a potential biocompatible material.


Yeast grown in continuous culture systems can detect mutagens with improved sensitivity relative to the Ames test.
Continuous culture systems allow for the controlled growth of microorganisms over a long period of time. Here, we develop a novel test for mutagenicity that involves growing yeast in continuous culture systems exposed to low levels of mutagen for a period of approximately 20 days. In contrast, most microorganism-based tests for mutagenicity expose the potential mutagen to the biological reporter at a high concentration of mutagen for a short period of time. Our test improves upon the sensitivity of the well-established Ames test by at least 20-fold for each of two mutagens that act by different mechanisms (the intercalator ethidium bromide and alkylating agent methyl methanesulfonate). To conduct the tests, cultures were grown in small, inexpensive continuous culture systems in media containing (potential) mutagen, and the resulting mutagenicity of the added compound was assessed via two methods: a canavanine-based plate assay and whole genome sequencing. In the canavanine-based plate assay, we were able to detect a clear relationship between the amount of mutagen and the number of canavanine-resistant mutant colonies over a period of one to three weeks of exposure. Whole genome sequencing of yeast grown in continuous culture systems exposed to methyl methanesulfonate demonstrated that quantification of mutations is possible by identifying the number of unique variants across each strain. However, this method had lower sensitivity than the plate-based assay and failed to distinguish the different concentrations of mutagen. In conclusion, we propose that yeast grown in continuous culture systems can provide an improved and more sensitive test for mutagenicity.


Use of gene expression microarrays for the study of acute leukemia.
Genetic lesions found in acute leukemia drive the pathology of the disease in addition to forming reliable classifications of prognosis. However, there is still a reasonable heterogeneity of response among cases with the same genetic lesion. Moreover, many leukemia cases have no detectable genetic marker and these cases have marked heterogeneity of response. How can we learn more about the genes and pathways involved with leukemogenesis and response in the midst of such complexity? Gene expression microarrays are experimental platforms that allow for the simultaneous evaluation of the thousands of mRNA transcripts (the 'transcriptome'). This technology has revolutionized the study of leukemia, giving insight into genes and pathways involved in disease response and the biology involved in specific translocations.


Overexpression of bone sialoprotein leads to an uncoupling of bone formation and bone resorption in mice.
The purpose of this study was to determine the effects of bone sialoprotein (BSP) overexpression in bone metabolism in vivo by using a homozygous transgenic mouse line that constitutively overexpresses mouse BSP cDNA driven by the cytomegalovirus (CMV) promoter. CMV-BSP transgenic (TG) mice and wildtype mice were weighed, and their length, BMD, and trabecular bone volume were measured. Serum levels of RANKL, osteocalcin, osteoprotegerin (OPG), TRACP5b, and PTH were determined. Bone histomorphometry, von Kossa staining, RT-PCR analysis, Western blot, MTS assay, in vitro mineralization assay, and TRACP staining were also performed to delineate phenotypes of this transgenic mouse line. Compared with wildtype mice, adult TG mice exhibit mild dwarfism, lower values of BMD, and lower trabecular bone volume. TG mice serum contained increased calcium levels and decreased PTH levels, whereas the levels of phosphorus and magnesium were within normal limits. TG mice serum also exhibited lower levels of osteoblast differentiation markers and higher levels of markers, indicating osteoclastic activity and bone resorption. H&E staining, TRACP staining, and bone histomorphometry showed that adult TG bones were thinner and the number of giant osteoclasts in TG mice was higher, whereas there were no significant alterations in osteoblast numbers between TG mice and WT mice. Furthermore, the vertical length of the hypertrophic zone in TG mice was slightly enlarged. Moreover, ex vivo experiments indicated that overexpression of BSP decreased osteoblast population and increased osteoclastic activity. Partly because of its effects in enhancing osteoclastic activity and decreasing osteoblast population, BSP overexpression leads to an uncoupling of bone formation and resorption, which in turn results in osteopenia and mild dwarfism in mice. These findings are expected to help the development of therapies to metabolic bone diseases characterized by high serum level of BSP.


Elemental Contrast X-ray Tomography Using Ross Filter Pairs with a Polychromatic Laboratory Source.
The majority of current laboratory based X-ray sources are polychromatic and are not tuneable. This lack of monochromaticity limits the range of applications for these sources and in particular it reduces the elemental specificity of laboratory based X-ray imaging experiments. Here we present a solution to this problem based on the use of Ross filter pairs. Although such Ross filter arrangements have been applied in proof-of-principle spectroscopy experiments, to date there have been no reports of this approach used for full-field X-ray imaging. Here we report on the experimental demonstration of Ross filter pairs being used for quasi-monochromatic, full-field imaging. This arrangement has several important benefits for laboratory based X-ray imaging including, as we demonstrate, elemental contrast enhancement. The method is demonstrated both for two-dimensional radiography and for three-dimensional X-ray tomography.


Increased duplex stabilization in porphyrin-LNA zipper arrays with structure dependent exciton coupling.
Porphyrins were attached to LNA uridine building blocks via rigid 5-acetylene or more flexible propargyl-amide linkers and incorporated into DNA strands. The systems show a greatly increased thermodynamic stability when using as little as three porphyrins in a zipper arrangement. Thermodynamic analysis reveals clustering of the strands into more ordered duplexes with both greater negative ΔΔS and ΔΔH values, and less ordered duplexes with small positive ΔΔS differences, depending on the combination of linkers used. The exciton coupling between the porphyrins is dependent on the flanking DNA sequence in the single stranded form, and on the nature of the linker between the nucleobase and the porphyrin in the double stranded form; it is, however, also strongly influenced by intermolecular interactions. This system is suitable for the formation of stable helical chromophore arrays with sequence and structure dependent exciton coupling.


[Pio Baroja, physician and novelist].
Some biographical details on Pio Baroja, important "98 Spanish generation" member, graduated as medical doctor with a brief work in the profession and later total consecretion to the literature. The author refers to Baroja's interesting polemics with some important Venezuelan writers so his personal acknowledgement on him and highlights the strong Pio Baroja's personality.


[Pneumonia among patients admitted to intensive care units. An epidemiological multicenter study of APACHE II score, incidence and course].
Pneumonia in patients in intensive care units (ICU) is associated with several diagnostic difficulties and high mortality. This study was conducted to describe the diagnostic procedures and clinical characteristics of the pneumonic and critically ill patient in relation to APACHE II score. The material consisted of 193 patients admitted to seven Danish ICUs and is also included in a European epidemiologic survey (EURO.NIS). Twenty-eight (14.5%) developed pneumonia and 18 (9.3%) of these were nosocomial (> 48h after admission). Patients with pneumonia had a significantly higher APACHE II score, duration of stay and mortality. The techniques used to diagnose pneumonia were mainly conventional and did not or only seldom include protected brush, bronchoalveolar lavage or pulmonary biosy. The predominant pathogens isolated in tracheal aspirate were Gram-negative bacilli (50%). The APACHE II scoring system was found to stratify patients with respect to mortality, duration of stay and pneumonia diagnosed in ICU.


Superoxide dismutase plus catalase therapy delays neither cell death nor the loss of the TTC reaction in experimental myocardial infarction in dogs.
Studies to test whether superoxide dismutase (SOD), with or without catalase, limits myocardial infarct size have produced conflicting results. Positive results following short periods of reperfusion vs negative results following longer periods of reperfusion could be explained if either: (1) myocytes, initially salvaged by SOD, are killed by continued production of free radicals after the administered SOD have been excreted, or (2) false positive results occur because SOD transiently preserves the TTC reaction, despite loss of cellular viability. To evaluate these two possibilities, we measured infarct size after 90 min of ischemia and 4 h of reperfusion in SOD+catalase treated and untreated dogs. Treated dogs received a 60 min intra-arterial infusion of SOD (15,000 U/kg) plus catalase (CAT) (55,000 U/kg) beginning 25 min before reperfusion. Infarct size was measured using triphenyl tetrazolium (TTC) macrochemistry and was compared with the extent of necrosis assessed semi-quantitatively by light microscopy. Mean infarct size was similar in the control and treated groups. In addition, there was a positive linear correlation (r = 0.95) between the extent of necrosis estimated by microscopy and that estimated by TTC in both groups, and treatment did not alter the regression line. These current results were compared with results from the control dogs from our previous study (Richard et al., 1988) in which 90 min of ischemia was followed by 4 days of reperfusion. TTC-based infarct size at 4 days of reperfusion was similar to that observed in both groups at 4 h. These data indicate that oxygen free radicals, accessible to intravascular SOD and catalase, are not a cause of myocyte death detectable by measurement of infarct size after 4 h of reperfusion. Moreover, neither an "early protection, delayed death" hypothesis nor a specific preservation of the TTC reaction explain the positive results of other studies. TTC macrochemistry provides reliable estimates of myocardial infarct size, provided that sufficient magnification is used to permit resolution of interdigitating peninsulas of viable and necrotic tissue.


Candidate Biomarkers in Children with Autism Spectrum Disorder: A Review of MRI Studies.
Searching for effective biomarkers is one of the most challenging tasks in the research field of Autism Spectrum Disorder (ASD). Magnetic resonance imaging (MRI) provides a non-invasive and powerful tool for investigating changes in the structure, function, maturation, connectivity, and metabolism of the brain of children with ASD. Here, we review the more recent MRI studies in young children with ASD, aiming to provide candidate biomarkers for the diagnosis of childhood ASD. The review covers structural imaging methods, diffusion tensor imaging, resting-state functional MRI, and magnetic resonance spectroscopy. Future advances in neuroimaging techniques, as well as cross-disciplinary studies and large-scale collaborations will be needed for an integrated approach linking neuroimaging, genetics, and phenotypic data to allow the discovery of new, effective biomarkers.


Exploring women's perspectives on prenatal screening for adverse childhood experiences.
To learn more about women's views on screening for adverse childhood experiences (ACEs) during healthcare visits in pregnancy. Mixed methods with an online survey. A convenience sample of 154 women with a history of one or more pregnancies was recruited through public health department social media pages in one predominantly rural region of a Midwest state. Quantitative measures included demographic variables, ACE scores, and preferences regarding screening format, strategies, and resources. Additional perspectives were captured through open-ended questions. Women's mean ACE score was 2.56 (SD = 2.37) with 68% reporting 0-3 ACEs and 32% reporting four or more. Routine screening for ACEs during prenatal care was supported by 67.5% of women with 9.1% indicating sometimes, 20.8% unsure, and 2.6% against. Strong preference was indicated for screening by one's physician or midwife (80.3%), in an exam room (83.1%), using an independently completed questionnaire (64.2%). Preferred approaches for screening and post-screening interventions also were identified with qualitative themes providing additional insights. Findings inform strategies for efficiently and sensitively screening for ACEs during pregnancy, highlight the importance of using a trauma-informed approach, and provide direction for educational and interventional resource development.


TOF-assisted binocular vision accuracy improvement method for underwater fish size inspection.
To address problems such as the lack of accuracy in acquiring depth maps for dynamic fish 3D measurements by usual binocular vision or a time-of-flight (TOF) depth camera, a TOF-assisted binocular vision depth acquisition algorithm is used to obtain high-quality depth maps. The TOF depth energy function is designed to guide the binocular stereo matching process, which improves the correct matching rate of binocular matching in low-texture regions; the TOF and binocular stereo matching confidence weighting functions are designed to achieve the fusion of the two at pixel level to improve the matching quality of fish in the occluded overlapping regions. The experimental results show that the TOF-assisted binocular vision system improves the accuracy of fish size measurement compared to single binocular vision while reducing the measurement error when the fish body has a significant inclination along the depth axis.


Do we have the evidence we need and are we communicating it well?
Despite the growth of evidence on the health and financial impact of workplace health promotion, experts in health policy and management are not aware of this evidence. To change this, we need to publish in their journals, speak at their conferences, and collaborate with them on evaluation and research. These collaborations have the additional advantage of our learning how to conduct population level analysis and express findings in the terms policy makers understand.


* Harnessing External Cues: Development and Evaluation of an In Vitro Culture System for Osteochondral Tissue Engineering.
Over the last decade, engineered structures have been developed for osteochondral (OC) tissue regeneration. While the optimal structure design is yet to be determined, these scaffolds require in vitro evaluation before clinical use. However, the means by which complex scaffolds, such as OC scaffolds, can be tested are limited. Taking advantage of a mesenchymal stem cell's (MSC's) ability to respond to its surrounding we harness external cues, such as the cell's mechanical environment and delivered factors, to create an in vitro culture system for OC tissue engineering with a single cell source on a gradient yet integrated scaffold system. To do this, the effect of hydrogel stiffness on the expression of human MSCs (hMSCs) chondrogenic differentiation was studied using histological analysis. Additionally, hMSCs were also cultured in different combinations of chondrogenic and osteogenic media to develop a co-differentiation media suitable for OC lineage differentiation. A uniquely graded (density-gradient matrix) OC scaffold with a distal cartilage hydrogel phase specifically tailored to support chondrogenic differentiation was cultured using a newly developed "simulated in vivo culture method." The scaffold's culture in co-differentiation media models hMSC infiltration into the scaffold and subsequent differentiation into the distal cartilage and proximal bone layers. Cartilage and bone marker staining along with specific matrix depositions reveal the effect of external cues on the hMSC differentiation. As a result of these studies a model system was developed to study and culture OC scaffolds in vitro.


Serum inhibitor in systemic lupus erythematosus associated with aplastic anemia.
Hematologic complications of systemic lupus erythematosus (SLE) usually involve peripheral destruction of blood elements. We report a case of SLE-associated aplastic anemia in which an IgG complement-dependent antibody, obtained from the patient's disease-phase serum but not remission-phase serum, suppressed growth of granulocyte-macrophage progenitor cells from bone marrow of normal donors in vitro. Therapy with plasmapheresis and immunosuppression resulted in lasting remission.


Motivation of Owners to Purchase Pedigree Cats, with Specific Focus on the Acquisition of Brachycephalic Cats.
Background: Cats are globally popular pets and pedigree cats are increasingly prevalent, with brachycephalic breeds being the most registered breeds. How owners decide upon and acquire their cats is poorly understood. Moreover, there are growing concerns about the health and welfare of brachycephalic (BC) dogs and recent studies are raising the awareness of health and welfare problems in BC cats. Methods: An online survey investigated owners' motivations, perceptions and behaviours prior to, during and following acquisition of non-pedigree (NP), extreme brachycephalic pedigree (BC; i.e., Persian and Exotic Shorthair) and mild to non-BC pedigree (P) cats. Results: The survey received 1367 valid responses (NP n = 882, P n = 400, BC n = 85 (6.2%)). There were marked differences between NP, P and BC owners' perception of their cats' health and welfare, reason(s) for acquisition and its process. Owners of NP were less influenced by appearance, behaviour and other features than P or BC owners. In contrast, P and BC owners were highly influenced by appearance, with P owners also placing greater importance on good breed health than BC owners. BC owners were less likely to recommend their breeds to prospective cat owners, apparently concerned by high maintenance requirements. Conclusion: Further research is needed to determine how decision-making is constructed and how it may be improved, especially in respect of welfare outcomes for extreme BC cats given the increased weighting given to appearance over health.


A method for determining transmembrane protein structure.
A simple and rapid protein chemical approach for determining the transmembrane structure of membrane proteins is described. The method involves single substitutions of consecutive amino acid residues, within putative transmembrane segments, to cysteine. This is followed by the analysis of their susceptibility to modification by maleimides with different physico-chemical properties. Fluorescein-5-maleimide (FM), being hydrophilic, modified only residues located in the aqueous environment, while the hydrophobic reagent, benzophenone-4-maleimide (BM) modified residues exposed to the lipid phase. These probes are large enough to cause an increase in the molecular weight of relatively small membrane proteins or polypeptide fragments, which is detectable by SDS-PAGE. Modification by much smaller probes, such as N-ethylmaleimide (NEM), could also be monitored indirectly by the ability to prevent SDS-solubilized protein from being modified with fluorescein-5-maleimide. The approach is demonstrated with the proteolipid complex of the vacuolar H(+)-ATPase expressed in yeast and with the putative Isk K(+)-channel expressed and radiolabelled in E. coli. The advantages of this approach are: (1)it is rapid, easy and inexpensive, (2) detection of the modification of engineered cysteines is simple, (3) it requires only minute quantities of the protein, (4) the protein does not require purification, (5) a broad range of maleimides with different physico-chemical properties can be used, (6) the structure can be investigated under native conditions and does not require protein reconstitution into artificial bilayers.


Simultaneously estimating the task-related and stimulus-evoked components of hemodynamic imaging measurements.
Task-related hemodynamic responses contribute prominently to functional magnetic resonance imaging (fMRI) recordings. They reflect behaviorally important brain states, such as arousal and attention, and can dominate stimulus-evoked responses, yet they remain poorly understood. To help characterize these responses, we present a method for parametrically estimating both stimulus-evoked and task-related components of hemodynamic responses from subjects engaged in temporally predictable tasks. The stimulus-evoked component is modeled by convolving a hemodynamic response function (HRF) kernel with spiking. The task-related component is modeled by convolving a Fourier-series task-related function (TRF) kernel with task timing. We fit this model with simultaneous electrode recordings and intrinsic-signal optical imaging from the primary visual cortex of alert, task-engaged monkeys. With high [Formula: see text], the model returns HRFs that are consistent across experiments and recording sites for a given animal and TRFs that entrain to task timing independent of stimulation or local spiking. When the task schedule conflicts with that of stimulation, the TRF remains locked to the task emphasizing its behavioral origins. The current approach is strikingly more robust to fluctuations than earlier ones and gives consistently, if modestly, better fits. This approach could help parse the distinct components of fMRI recordings made in the context of a task.


Pure PBL, Hybrid PBL and Lecturing: which one is more effective in developing cognitive skills of undergraduate students in pediatric nursing course?
Nursing education in Iran has conventionally focused on lecture-based strategies. Improvements in teaching and learning over the years have led to an expansion of the pedagogies available to educators. Likewise, there has been a suggestion for a move toward more learner-centered teaching strategies and pedagogies that can result in improvement in learning. This study was undertaken to investigate the effects of Problem-Based Learning in developing cognitive skills in learning Pediatric Nursing among university students. In this quasi-experimental, posttest-only nonequivalent control group design, the subjects were undergraduate students who had enrolled in Pediatric Nursing II at Islamic Azad University in Iran. The experiment was conducted over a period of eight weeks, one two-hour session and two two-hour sessions. Two experimental groups, Pure Problem-Based Learning (PPBL) and the Hybrid Problem- Based Learning (HPBL), and one Lecturing or Conventional Teaching and Learning (COTL) group were involved. In the PPBL group, PBL method with guided questions and a tutor, and in the HPBL group, problem-based learning method, some guided questions, minimal lecturing and a tutor were used. The COTL group, however, underwent learning using conventional instruction utilizing full lecture. The three groups were compared on cognitive performances, namely, test performance, mental effort, and instructional efficiency. Two instruments, i.e., Pediatric Nursing Performance Test (PNPT) and Paas Mental Effort Rating Scale (PMER) were used. In addition, the two-Dimensional Instructional Efficiency Index (IEI) formula was utilized. The statistical analyses used were ANOVA, ANCOVA, and mixed between-within subjects ANOVA. Results showed that the PPBL and HPBL instructional methods, in comparison with COTL, enhanced the students' overall and higher-order performances in Pediatric Nursing, and induced higher level of instructional efficiency with less mental effort (p < 0.005). Although there was no significant difference in lower-order performance among the groups during the posttest (p = 0.92), the HPBL group outperformed the COTL group on the delayed posttest (p = 0.028). It may be concluded that both forms of PBL were effective for learning Pediatric Nursing. Moreover, PBL appears to be useful where there are shortages of instructors for handling teaching purposes.


Poly(ADP-ribose) binds to specific domains of p53 and alters its DNA binding functions.
DNA strand breaks are potential interaction sites for the nuclear enzyme poly(ADP-ribose) polymerase (PARP; E.C. 126.96.36.199) and the tumor suppressor protein p53. Both proteins bind and respond to DNA breaks and both play a role in DNA damage signaling. A temporary colocalization and complex formation between these proteins has been demonstrated in mammalian cells. Here we show that free and poly(ADP-ribose) polymerase-bound ADP-ribose polymers target three domains in p53 protein for strong noncovalent interactions. The polymer binding sites could be mapped to two amino acid sequences in the sequence-specific core DNA binding domain of p53 (amino acid positions 153-178 and 231-253) and another one in the oligomerization domain (amino acids 326-348). In mobility shift experiments, poly(ADP-ribose) effectively prevented and reversed p53 binding to the palindromic p53 consensus sequence. Additionally, poly(ADP-ribose) also interfered with the DNA single strand end binding of p53. The results suggest that ADP-ribose polymers could play a role in regulating the DNA binding properties of p53.


Three-Dimensional Free Chlorine and Monochloramine Biofilm Penetration: Correlating Penetration with Biofilm Activity and Viability.
Disinfectant biofilm penetration and its effect on biofilm aerobic activity and viability are still unclear. In this study, free chlorine and monochloramine were applied until full biofilm penetration occurred, and their effects on biofilm aerobic activity and viability were investigated in three dimensions throughout the entire biofilm depth, extending previous work where viability analysis was limited to the upper biofilm (50 μm depth), free chlorine penetration did not reach completion, and only one-dimensional (depth) profiles were obtained. The free chlorine and monochloramine biofilm concentration profiles were correlated spatially and temporally with aerobic microbial activity and cell-membrane integrity based viability using a combination of (1) microelectrode measurements for disinfectant penetration and (2) LIVE/DEAD BacLight staining, cryo-cross-sectioning, and confocal micrographs analysis for viability measurements throughout the entire biofilm depth. Compared to monochloramine, free chlorine penetration (1) was slower, (2) led to a greater decrease in biofilm thickness from sloughing, and (3) corresponded directly with a viability decrease. In addition, biofilm heterogeneity led to minor differences in either disinfectant's biofilm penetration, and prior biofilm exposure to monochloramine provided little impact to subsequent free chlorine biofilm penetration.


Antagonistic Center-Surround Mechanisms for Direction Selectivity in the Retina.
An antagonistic center-surround receptive field is a key feature in sensory processing, but how it contributes to specific computations such as direction selectivity is often unknown. Retinal On-starburst amacrine cells (SACs), which mediate direction selectivity in direction-selective ganglion cells (DSGCs), exhibit antagonistic receptive field organization: depolarizing to light increments and decrements in their center and surround, respectively. We find that a repetitive stimulation exhausts SAC center and enhances its surround and use it to study how center-surround responses contribute to direction selectivity. Center, but not surround, activation induces direction-selective responses in SACs. Nevertheless, both SAC center and surround elicited direction-selective responses in DSGCs, but to opposite directions. Physiological and modeling data suggest that the opposing direction selectivity can result from inverted temporal balance between excitation and inhibition in DSGCs, implying that SAC's response timing dictates direction selectivity. Our findings reveal antagonistic center-surround mechanisms for direction selectivity and demonstrate how context-dependent receptive field reorganization enables flexible computations.


Application of Metabolic Profiling to Abdominal Aortic Aneurysm Research.
Abdominal aortic aneurysm (AAA) is a complex disease posing diagnostic and therapeutic challenges. Metabonomics may aid in the diagnosis of AAA, determination of individualized risk, discovery of therapeutic targets, and improve understanding of pathogenesis. A systematic review of the diversity and outcomes of existing AAA metabonomic research has been performed. Original research studies applying metabonomics to human aneurysmal disease are included. Seven relevant articles were identified: four studies were based on plasma/serum metabolite profiling, and three studies examined aneurysmal tissue. Aminomalonic acid, guanidinosuccinic acid, and glycerol emerge as potential plasma biomarkers of large aneurysm. Lipid profiling improves predictive models of aneurysm presence. Patterns of metabolite variation associated with AAA relate to carbohydrate and lipid metabolism. Perioperative perturbations in metabolites suggest differential systemic inflammatory responses to surgery, generating hypotheses for adjunctive perioperative therapy. Significant limitations include small study sizes, lack of correction for multiple testing false discovery rates, and single time-point sampling. Metabolic profiling carries the potential to identify biomarkers of AAA and elucidate pathways underlying aneurysmal disease. Statistically and methodologically robust studies are required for validation, addressing the hiatus in understanding mechanisms of aneurysm growth and developing effective treatment strategies.


Central pontine myelinolysis.
In 1949, Victor and Adams observed an alcoholic patient who developed quadriplegia and pseudobulbar palsy, and inability to chew, talk or swallow. A post-mortem confirmed their suspicion of 'a large, symmetrical, essentially demyelinative lesion occupying the greater part of the basis pontis.' This paper follows the historical evolution of central pontine myelinolysis and the changing concepts of its metabolic aetiology. Too rapid a rate of correction of hyponatraemia is the most common, but not invariable aetiology.


Fruit Detection and Pose Estimation for Grape Cluster-Harvesting Robot Using Binocular Imagery Based on Deep Neural Networks.
Reliable and robust fruit-detection algorithms in nonstructural environments are essential for the efficient use of harvesting robots. The pose of fruits is crucial to guide robots to approach target fruits for collision-free picking. To achieve accurate picking, this study investigates an approach to detect fruit and estimate its pose. First, the state-of-the-art mask region convolutional neural network (Mask R-CNN) is deployed to segment binocular images to output the mask image of the target fruit. Next, a grape point cloud extracted from the images was filtered and denoised to obtain an accurate grape point cloud. Finally, the accurate grape point cloud was used with the RANSAC algorithm for grape cylinder model fitting, and the axis of the cylinder model was used to estimate the pose of the grape. A dataset was acquired in a vineyard to evaluate the performance of the proposed approach in a nonstructural environment. The fruit detection results of 210 test images show that the average precision, recall, and intersection over union (IOU) are 89.53, 95.33, and 82.00%, respectively. The detection and point cloud segmentation for each grape took approximately 1.7 s. The demonstrated performance of the developed method indicates that it can be applied to grape-harvesting robots.


A 10-Year Clinical Experience of Gestational Trophoblastic Disease at Rajavithi Hospital, 2001-2010.
Gestational trophoblastic disease (GTD) develops from abnormal cellular proliferation of trophoblasts following fertilization and is categorized as either an hydatidiform mole (HM) or a gestational trophoblastic neoplasia (GTN). To analyze the clinical characteristics, incidence and treatment outcomes of GTD at Rajavithi Hospital. Medical records of women diagnosed with GTD at Rajavithi Hospital from January 1, 2001 to December 31, 2010 were retrospectively reviewed. Disease diagnosis, treatment and follow-up data were analyzed. A total of 329 cases of GTD were reviewed. HM was diagnosed in 167 patients (incidence 2.32 per 1,000 deliveries); 26 patients were lost to follow-up; and 49 of the remaining 141 patients (34.8%) developed post-molar GTN. In multivariable analysis, uterus >16 week size and pre-treatment human chorionic gonadotropin (hCG) level >250,000 mIU/mL were the significant risk factors for developing post-molar GTN. Of 162 patients with GTN (incidence 2.25 per 1,000 deliveries), 15 patients were lost to follow-up, and 116 patients, 29 patients and 2 patients were classified as having low-risk GTN, high-risk GTN and placental site trophoblastic disease respectively. The overall survival rate in the low-risk group was 100% whereas in the high-risk group it was 86.2%. A modified WHO prognostic score of more than five was the significant risk factor for developing resistant GTN. GTD treatment at Rajavithi Hospital showed excellent clinical outcomes. Uterus >16 weeks size and pre- treatment hCG > 250,000 mIU/mL were the significant risk factors for developing post-molar GTN in HM patients. Classifying GTN patients into low- and high-risk groups was useful in planning treatment and counseling.


Access to pathology and laboratory medicine services: a crucial gap.
As global efforts accelerate to implement the Sustainable Development Goals and, in particular, universal health coverage, access to high-quality and timely pathology and laboratory medicine (PALM) services will be needed to support health-care systems that are tasked with achieving these goals. This access will be most challenging to achieve in low-income and middle-income countries (LMICs), which have a disproportionately large share of the global burden of disease but a disproportionately low share of global health-care resources, particularly PALM services. In this first in a Series of three papers on PALM in LMICs, we describe the crucial and central roles of PALM services in the accurate diagnosis and detection of disease, informing prognosis and guiding treatment, contributing to disease screening, public health surveillance and disease registries, and supporting medical-legal systems. We also describe how, even though data are sparse, these services are of both insufficient scope and inadequate quality to play their key role in health-care systems in LMICs. Lastly, we identify four key barriers to the provision of optimal PALM services in resource-limited settings: insufficient human resources or workforce capacity, inadequate education and training, inadequate infrastructure, and insufficient quality, standards, and accreditation.


Experimental model of heterotopic cardiac transplantation for evaluation of graft viability and function.
An experimental model of heterotopic intrathoracic cardiac transplantation making possible an evaluation of graft viability and function has been studied. The technique requires only two anastomoses in the normothermic state without cardiopulmonary bypass. In this model, the ascending aorta of the recipient animal may be occluded completely, enabling an increasing preload on the graft. In case of adequate myocardial preservation of the cardiac graft, the aorta may be completely occluded and the recipient systemic circulation can be sustained by the graft. However, in case of inadequate graft myocardial function, or in case of size mismatch, the recipient heart alone contributes to the circulation. This technique appears quite useful because of its simplicity, the elimination of the need for extracorporeal circulation while allowing a functional evaluation following cardiac graft preservation.


Aminoglycoside-induced hearing loss in a patient with the 961 mutation in mitochondrial DNA.
The A1555G mutation in the mitochondrial 12S ribosomal RNA gene is often found in patients with hearing loss after aminoglycoside exposure. A second pathogenic mutation in this gene, deletion of thymidine at position 961 with varying numbers of cytosines inserted (delT961Cn), has recently been found to predispose patients to aminoglycoside-induced deafness. We report on a Japanese patient bearing the delT961Cn who had streptomycin-induced deafness. Our report suggests that the delT961Cn plays an important secondary role in the pathogenesis of deafness caused by aminoglycosides. The combination of taking family histories and molecular screening at the 1555 and 961 positions is thought to reduce the frequency of tragic irreversible deafness due to aminoglycosides.


Clinical Implications of the Progression-Free Survival Endpoint for Treatment of Hormone Receptor-Positive Advanced Breast Cancer.
: Hormonal therapy for advanced breast cancer (ABC) has evolved significantly since the introduction of tamoxifen more than 40 years ago. The availability of selective antiestrogen therapies has further improved treatment options for women with hormone receptor-positive (HR+) ABC. However, with the development of resistance to hormonal therapies, a new treatment paradigm has emerged based on our understanding of biological pathways involved in HR+ breast cancer and mechanisms of resistance to hormonal therapy. Recent drug development efforts have focused on combining hormonal treatment with agents that target mammalian target of rapamycin serine-threonine kinases and cyclin-dependent kinases. In parallel with the evolution of hormonal and targeted therapies, our understanding of the utility of clinical endpoints has deepened. Progression-free survival (PFS) is a primary endpoint well-understood by clinicians and is increasingly accepted as a surrogate for overall survival (OS) by the U.S. Food and Drug Administration. Yet the perceived clinical benefit of PFS to patients is less well understood. Patients may not grasp the implications of prolonged PFS, highlighting the reality that patient preference in treatment selection encompasses factors that extend beyond drug activity. This presents an opportunity for clinicians to discuss PFS with patients in the context of their treatment plans, clinical outcomes, and quality-of-life measures. The objective of this review is to explore the clinical validity of the PFS and OS endpoints and the clinical relevance of PFS and OS to patients, especially in light of drivers that led to a range of treatment options for patients with HR+ ABC. Advances in drug development during the past two decades have provided numerous options for treatment of advanced breast cancer that include monotherapy with endocrine modulating agents and dual therapy that combines endocrine therapy with an inhibitor targeting the mammalian target of rapamycin serine-threonine kinase or cyclin-dependent kinase pathways known to be involved with resistance. Clinical trial endpoints for breast cancer have evolved as well. Communication of progression-free survival, overall survival, and other outcomes with patients should incorporate the context of the individual's treatment plan and include discussion of response rate, side effects, and quality of life.


Impact of traveling to visit friends and relatives on chronic disease management.
Travelers visiting friends and relatives (VFR) are known to be at high risk of acquiring infectious diseases during travel. However, little is known about the impact of VFR travel on chronic diseases. This was a nonrandomized, retrospective observational study. Patients were adult VFR travelers who received care from an internal medical clinic serving immigrants and refugees. The primary objective was to determine the impact of VFR travel on markers of chronic disease management including: blood pressure, glycosylated hemoglobin, body mass index, serum creatinine, and anticoagulation. Of the 110 VFR travelers in our study, N = 48 traveled to Africa and N = 62 traveled to Asia for a mean duration of 59 (range 21-303) days. Of the 433 counseling points discussed at pre-travel visits, 71% were infectious disease prevention, 16% chronic disease related, and 13% travel safety. A total of 63 patients (57%) reported one or more health problems while traveling. Of these, 35 patients (32%) experienced a problem related to a chronic condition. In comparison, 24 (22%) patients experienced an acute infection. Sixty percent of patients were nonadherent to medications during travel. An average increase in diastolic blood pressure of 3.6 mmHg among patients with hypertension was the only statistically significant change in a chronic disease marker when values before and after travel were compared. Subgroup analysis revealed that travel to Africa and nonadherence to medications were also associated with worsening blood pressure control, and patients traveling to Africa experienced a decrease in body mass index. This study identified a high proportion of problems related to chronic conditions experienced during VFR travel, while pre-travel appointments tended to focus on infectious disease prevention. A greater emphasis on medication adherence and chronic disease management during VFR travel is also needed during pre-travel preparations.


[Interstitial afterloading therapy. Principles, practical application and first clinical experiences].
The principle and practical application of an afterloading system for interstitial therapy is reported. The system works with a single Ir-192 source with high dose rate and achieves the optimum dose distribution by gradual displacement and variable position times. A specially developed computer program serves to calculate the stopping times of the source. The implantation is performed with hollow needles made of refined steel, which are held in parallel position by means of jigs fixed to the patient. 28 patients with 36 tumors have been treated. The dose was determined according to the experiences in gynecologic afterloading therapy with high dose rate sources and dosage prescriptions in teletherapy. The authors present the therapeutic results of this pilot study, discuss the new system and show practicable possibilities for further development.


Coffea arabica bean extract inhibits glucose transport and disaccharidase activity in Caco-2 cells.
The major constituents of Coffea arabica (coffee), including caffeine, chlorogenic acid and caffeic acid, exhibit antihyperglycemic properties in in vitro and in vivo models. However, whether Coffea arabica bean extract (CBE) regulates glucose uptake activity and the underlying mechanisms involved remain unclear. The aim of the present study was to examine the effects of CBE on glucose absorption and identify the mechanisms involved using an in vitro model. The uptake of a fluorescent glucose analog into Caco-2 colorectal adenocarcinoma cells was determined. The expression levels of sodium glucose co-transporter 1 (SGLT1) and glucose transporter 2 (GLUT2) were evaluated. In addition, glycoside hydrolase enzyme activity was investigated. It was observed that CBE inhibited disaccharidase enzyme activity. Furthermore, CBE exerted an inhibitory effect on intestinal glucose absorption by downregulating SGLT1- and GLUT2-mediated 5' AMP-activated protein kinase phosphorylation and suppressing hepatocyte nuclear factor 1α expression. These data suggest that CBE may attenuate glucose absorption and may have potentially beneficial antihyperglycemic effects in the body; however, the mechanisms underlying the effects of CBE must be elucidated through further investigation.


[Expression and significance of MMP-9, PR, Ki-67 and Survivin in multiple meningiomas].
To detect the expressions of matrix metalloproteinase-9(MMP-9), progesterone receptor(PR), Ki-67 and Survivin in the multiple meningiomas (MMs) and explore its genesis, diagnosis and bionomics features. A total of 66 cases with histological sections of meningiomas retrieved from the archives of Department of Pathology of our hospital, including 30 cases of solitary meningiomas (SMs) and 36 cases MMs, were regrouped as benign, atypical and malignant by hematoxylin and eosin staining according to the World Health Organization classification of nervous system tumors. Immunohistochemistry was performed to detect the expressions of MMP-9, PR, Ki-67 and Survivin in 36 cases of MMs and 30 cases of SMs. And normal brain tissue was selected as a control group. The staining intensity was analyzed quantitatively for the differential expressions of MMP-9, PR, Ki-67 and Survivin between SMs and MMs. No expression of MMP-9, PR, Ki-67 and Survivin was detected in 5 normal brain tissues, but the expression rates were 100%, 53%, 23% and 88% respectively for significant difference comparing with normal tissue. The result of statistical analysis showed that there was significant difference in the expression intensity of MMP-9 and PR between two groups. The expression intensity MMP-9 in multiple group was significantly higher in MMs than that in SMs (P < 0.01) while PR was lower in MMs than that in SMs (P < 0.05). But no significant difference was found for the expression of Ki-67 or Survivin between two groups. The detections of MMP-9, PR, Ki-67 and Survivin are helpful in the clinical diagnosis and early detection of meningioma.


Partial coupling delay induced multiple spatiotemporal orders in a modular neuronal network.
The influence of partial coupling delay on the spatiotemporal spiking dynamics is explored in a modular neuronal network. The modular neuronal network is composed of two subnetworks which present the small-world property and scale-free property, respectively. Numerical results show that spatiotemporal order that the modular network is most coherent in time and nearly synchronized in space can emerge intermittently when the coupling delays among neurons are appropriately tuned. The appropriately tuned delays are further detected to be integer multiples of the intrinsic spiking period of the modular neuronal network, which implies that the phenomenon of multiple spatiotemporal orders could be the result of a locking between the length of coupling delay and the intrinsic spiking period of the modular neuronal network. Moreover, the multiple spatiotemporal orders are verified to be robust against variations of the fraction of delayed connection as well as the key parameters of network architecture such as the rewiring probability, the average degree of small-world subnetwork, the initial nodes of scale-free subnetwork and the total size of the modular network.


Modified calibration protocols in electron beam dosimetry: comparison with IAEA TRS-398 and AAPM TG-51.
This study aimed to compare absolute calibration outputs based on the protocols of the International Atomic Energy Agency (IAEA) Technical Report Series (TRS)-398, the American Association of Physicists in Medicine (AAPM) Task Group (TG)-51, and modified calibration approach. The electron beam output calibration followed the IAEA TRS-398 and AAPM TG-51 protocols, both of which required cylindrical chambers and parallel plates. However, the use of cylindrical chambers is not recommended at low energies because of the large fluence-correction factor. TG-51 recommended cross-calibration of the parallel-plate chamber against the cylindrical chamber in a high-energy electron beam. In 2020, an electron beam dosimetry modification was introduced that used a cylindrical ionisation chamber at all energies and updated the data for beam quality conversion factors. This modification provided a lower deviation than that reported in AAPM TG-51. Thus, the modified calibration based on TRS-398 was applied in the present study, which yielded results below the permissible tolerance. The beam calibration at 6, 8, 10, 12, and 15 MeV energies was carried out for two Elekta linear accelerators.. Electron beam dosimetry followed the AAPM TG-51 and TRS-398 protocols, and modified calibration were performed to measure the dose at the maximum depth expressed in dose/monitor units (cGy/MU). Charge-reading measurements were measured using ionisation chambers PTW 30013, IBA CC13, and Exradin A11. The average absorbed dose ratios were 1.004 and 1.009 using the modified calibration and TRS-398 and modified calibration and TG-51, respectively. Therefore, based on IAEA TRS-398, the results were below the tolerance limit (±2%).


Implementation of new technologies designed to improve cervical cancer screening and completion of care in low-resource settings: A case study from the Proyecto Precancer.
This case study details the experience of the Proyecto Precancer in applying the Integrative Systems Praxis for Implementation Research (INSPIRE) research methodology to guide the co-development, planning, implementation, adoption, and sustainment of new technologies and screening practices in a cervical cancer screening and management program in the Peruvian Amazon. We briefly describe the theoretical grounding of the INSPIRE framework, the phases of the INSPIRE process, the activities within each phase, and the RE-AIM outcomes used to evaluate program outcomes. Proyecto Precancer iteratively engaged over 90 stakeholders in the Micro Red Iquitos Sur (MRIS) health network in the Amazonian region of Loreto, Perú through the INSPIRE phases. INSPIRE is an integrative research methodology grounded in systems thinking, participatory action research, and implementation science frameworks such as the Consolidated Framework for Implementation Research. An interrupted time-series design with a mixed-methods RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) evaluation framework was used to examine the adoption of molecular-based primary cervical cancer screening using HPV-testing (including self-sampling), with direct treatment after visual inspection with portable thermal ablation at the primary level. The participatory and system-thinking-oriented approach led to rapid adoption and successful implementation of the new cervical cancer screening and management program within 6 months, using an HPV-based screen-and-treat strategy across 17 health facilities in one of the largest public health networks of the Peruvian Amazon. Monitoring and evaluation data revealed that, within 6 months, the MRIS had surpassed their monthly screening goals, tripling their original screening rate, with approximately 70% of HPV-positive women reaching a completion of care endpoint, compared with around 30% prior to the new CCSM strategy. Proyecto Precancer facilitated the adoption and sustainment of molecular-based primary cervical cancer screening using HPV-testing (including self-sampling), with direct treatment after visual inspection with portable thermal ablation at the primary level and the de-implementation of existing visual inspection-based screening strategies and colposcopy for routine precancer triage at the hospital level. This case study shows how PP used implementation science approaches to guide the adoption of a new screen-and-treat strategy in the Peruvian Amazon, while facilitating de-implementation of older screening practices.


A Randomized Controlled Trial of a Behavioral Weight Loss Program for Human Immunodeficiency Virus-Infected Patients.
Obesity compounds the negative health effects of human immunodeficiency virus (HIV) infection. We conducted the first randomized trial of behavioral weight loss for HIV-infected patients (n = 40). Participants randomized to an Internet behavioral weight loss program had greater 12-week weight loss (mean, 4.4 ± 5.4 kg vs 1.0 ± 3.3 kg; P = .02) and improvements in quality of life than controls. Clinical Trials Registration NCT02421406.


Atorvastatin prevents carbohydrate response element binding protein activation in the fructose-fed rat by activating protein kinase A.
High fructose intake contributes to the overall epidemic of obesity and metabolic disease. Here we examined whether atorvastatin treatment blocks the activation of the carbohydrate response element binding protein (ChREBP) in the fructose-fed rat. Fructose feeding increased blood pressure (21%, P < 0.05), plasma free fatty acids (59%, P < 0.01), and plasma triglyceride levels (129%, P < 0.001) compared with control rats fed standard chow. These increases were prevented by atorvastatin. Rats fed the fructose-rich diet showed enhanced hepatic messenger RNA (mRNA) levels of glycerol-3-phosphate acyltransferase (Gpat1) (1.45-fold induction, P < 0.05), which is the rate-limiting enzyme for the synthesis of triglycerides, and liver triglyceride content (2.35-fold induction, P < 0.001). Drug treatment inhibited the induction of Gpat1 and increased the expression of liver-type carnitine palmitoyltransferase 1 (L-Cpt-1) (128%, P < 0.01). These observations indicate that atorvastatin diverts fatty acids from triglyceride synthesis to fatty acid oxidation, which is consistent with the reduction in liver triglyceride levels (28%, P < 0.01) observed after atorvastatin treatment. The expression of Gpat1 is regulated by ChREBP and sterol regulatory element binding protein-1c (SREBP-1c). Atorvastatin treatment prevented fructose-induced ChREBP translocation and the increase in ChREBP DNA-binding activity while reducing SREBP-1c DNA-binding activity. Statin treatment increased phospho-protein kinase A (PKA), which promotes nuclear exclusion of ChREBP and reduces its DNA-binding activity. Human HepG2 cells exposed to fructose showed enhanced ChREBP DNA-binding activity, which was not observed in the presence of atorvastatin. Furthermore, atorvastatin treatment increased the CPT-I mRNA levels in these cells. Interestingly, both effects of this drug were abolished in the presence of the PKA inhibitor H89. These findings indicate that atorvastatin inhibits fructose-induced ChREBP activity and increases CPT-I expression by activating PKA.


Use of multiple overlapping sirolimus-eluting stents for treatment of long coronary artery lesions: results from a single-center registry in 318 consecutive patients.
Drug-eluting stents (DES) are superior to bare metal stents in the prevention of restenosis and target lesion revascularization (TLR). This has led to a more aggressive use of DES in everyday interventional cardiology practice. All consecutive patients who underwent coronary artery stenting with greater than 34 mm of overlapping, sirolimus-eluting stent (SES) were reviewed from a prospectively created database. A prespecified group of patients with greater than 60 mm of SES was also followed. 318 patients were followed up at a minimum of 6 months and a mean of 9 months. The mean target lesion stented length was over 55 mm. Use of IVUS was 19.8%. Forty patients (12.6%) suffered a peri-procedural CK-MB rise. The MACE rate at 9 months was 17% with 12.6% being periprocedural myocardial infarction (MI). Clinically driven TLR was 4.4% and cardiac death was 1.3%. There were 4 cases defined as late stent thrombosis. The independent predictors of periprocedural MI were the presence of a major side branch and longer target lesion stented length, with stable angina being a negative predictor. The independent predictors of in-stent restenosis were unstable angina and target lesion number per patient. There was a trend to increased MACE in the subgroup with longer than 60 mm of SES length. The use of multiple, overlapping SES is safe and effective with an acceptably low follow up MACE rate. A significant peri-procedural CK-MB rise appears to be a risk of long segment stenting. Whether this translates to long-term sequelae needs further investigation.


Synthesis Of Pyrido-Annelated Seven-Membered N-Containing Heterocycles.
Pharmaceutical industry is struggling with a lack of potential drugs in the pipe line. However, there is still a great opportunity to elaborate interesting scaffolds for medicinal chemistry. Various scaffolds that hold promise are rarely described in the literature. The last couple of decades, the wide range of biological activities of benzodiazepine derivatives have been investigated thoroughly and make the benzodiazepine scaffold, particularly the 1,4-benzodiazepine system, one of the most important structures for drug discovery. The substantial research on benzodiazepines has led to the synthesis of heterocycle-fused azepine derivatives with potentially new pharmacological activity. Some pyridoazepines are known to be active in the central nervous system and have a comparable activity to the well-known benzodiazepine scaffolds, which make the synthesis and study of pyridoazepines an important research topic.


[Silent ischemia--what should be done?].
The prevalence of silent, previously undiagnosed, exercise-induced ischemia is between 0.5 und 3.5% in 40-59-year-old men. Its prevalence is dependent upon the prevalence of coronary artery disease in the population or sub-population considered. The pathophysiological mechanism of silent ischemia is extracardiac. The prognosis of silent ischemia is determined by the functional impairement and the extent of coronary artery disease. The decision concerning medical and surgical treatment of patients with silent ischemia is based on the same criteria as in patients with ischemia and angina pectoris: patients at high risk (ischemia at low levels of exercise, marked exercise-induced ischemia, proximal 3-vessel disease and at least moderately impaired left ventricular function) are candidates for invasive treatment. Patients with ischemia at high levels of exercise, or with minimal ischemia with one- or two-vessel disease, are candidates for medical management. The best possible control of all cardiovascular risk factors is mandatory for all patients, from the viewpoint of prognosis in particular.


Sulfur-Switch Ugi Reaction for Macrocyclic Disulfide-Bridged Peptidomimetics.
A general strategy is introduced for the efficient synthetic access of disulfide linked artificial macrocycles via a Ugi four-component reaction (U4CR) followed by oxidative cyclization. The double-mercapto input is proposed for use in the Ugi reaction, thereby yielding all six topologically possible combinations. The protocol is convergent and short and enables the production of novel disulfide peptidomimetics in a highly general fashion.


Identification of tunnels in proteins, nucleic acids, inorganic materials and molecular ensembles.
The knowledge of the access paths connecting interior of molecular systems with surrounding environment is important for the understanding of structurefunction relationships and engineering of molecules for biotechnological applications. CAVER is a computer program developed for calculations of tunnels, channels or pores in the biomolecules, inorganic materials and molecular ensembles. The algorithm performs a skeleton search based on a reciprocal distance function grid. The algorithm is implemented in the stand-alone version, web version and as plug-in for PyMol. CAVER is available from the website http://loschmidt.chemi.muni.cz/caver.


Characteristics of koala (Phascolarctos cinereus adustus) semen collected by artificial vagina.
Collection of semen using a modified ovine artificial vagina was attempted on 90 occasions from 25 Queensland koalas (Phascolarctos cinereus adustus). Complete ejaculates consisting of a copulatory plug and sperm fraction were collected on 36 occasions (40%) from 19 animals. Seventeen of the males produced a complete ejaculate on their first or second service. Failure to collect semen (38%) and the collection of partial ejaculates (14.5%) was attributed to lack of sexual interest, aggressive behaviour towards the female by the male, the use of non-compliant teaser females or a distinct dislike of the artificial vagina. Only a few ejaculates were contaminated with urine (4.5%) or obtained after ejaculation behaviour was terminated (3%). The mean (+/-SEM) values for the seminal characteristics of 19 complete ejaculates were: mass of copulatory plug fraction 0.78 +/- 0.10 g, sperm fraction volume 0.73 +/- 0.10 ml, sperm concentration 165.1 +/- 26.7 x 10(6) ml-1, pH of sperm fraction 6.7 +/- 0.2, osmolarity of sperm fraction 315.0 +/- 5.4 mOsm, percentage forward motility 70.7 +/- 1.8%, rate of sperm movement 4.0 +/- 0.1 and percentage of abnormal spermatozoa 26.9 +/- 2.5%. Percentages of sperm head morphotypes and tail abnormalities were documented. Although the artificial vagina technique is limited by the need for access to oestrous females, the procedure described has been shown to be a simple, reliable method of collecting semen from captive koalas.


[Effects of abrupt salinity stress on osmoregulation of juvenile Rachycentron canadum].
Rachycentron canadum is a thriving mariculture species for offshore cage in southern Mainland and Taiwan of China, due to its rapid growth rate and high quality flesh. In this paper, the gill Na(+)-K+ ATPase (NKA) activity and iono- and osmoregulation of juvenile R. canadum were investigated in a 12 h stress of ambient salinities (0-45), and the results showed that after an abrupt transfer to the salinities of 0, 5, 15, 25, 37 (control) and 45, the death of juvenile R. canadum only occurred in salinity 0, with a mortality of 100% by the end of the experiment. In all treatments, the gill NKA activity and serum osmolality fluctuated in first 3 h, and then changed smoothly. The NKA activity varied with salinity grade in U shape, being significantly (P < 0.05) higher in salinity 5 and the lowest in salinity 15 in 12 h, while the serum osmolality (ranged 293-399 mOsmol x kg(-1)) presented a positive correlation with salinity. Serum [Na+] and [Cl-] concentration slightly increased with salinity within the period of 3-12 h, while serum [K+] displayed a reverse pattern. The isosmotic point was estimated as 328.2 mOsm x kg(-1) and corresponded to salinity 11.48. The isoionic points for serum [Na+], [K+] and [Cl-] were estimated as 155.2, 6.16, and 137.1 mmol x L(-1), which corresponded to the salinities of 10.68, 20.44 and 8.41, respectively. It was concluded that R. canadum could be characterized physiologically as a "higher-NKA-in-hyposmotic media" marine euryhaline teleost with the capability of rapid and effective hyper/hypo iono- and osmoregulation.


Interrelationship of reverse transcriptases of primate type D retroviruses.
Enzyme neutralization experiments by using an antiserum to reverse transcriptase (RT) of Mason-Pfizer monkey virus (MPMV) demonstrated the presence of common antigenic determinants on the RTs of all known type D retroviruses and of determinants discriminating different isolates. The RT of MPMV is antigenically closely related to the RTs of type D viruses isolated from human cell lines although significant differences are also detectable. It shows a lesser degree of relationship to the RTs of squirrel monkey retrovirus (SMRV) and of langur virus (PO-1-Lu). Since the major structural proteins of MPMV and PO-1-Lu are much more related to each other than to the corresponding protein of SMRV it can be concluded that there is no correlation in the degree of relatedness of different proteins of different type D viruses.


Complication Rates for Fluoroscopic Guided Interlaminar Lumbar Epidural Steroid Injections Performed by Certified Registered Nurse Anesthetists in Diverse Practice Settings.
What is the complication rate for Certified Registered Nurse Anesthetists (CRNAs) performing fluoroscopic guided lumbar epidural steroid injections (LESIs)? CRNA pain practitioners responded to questionnaires regarding their education level, experience, and practice locations. Participants also collected data on number of fluoroscopic guided LESIs performed and each of 20 complications for a 6-month period, and answered a poll regarding satisfaction with the data collection process. Participants represented urban (23%) and rural (77%) practices; as well as office/clinic (31%) hospital (62%) and mixed (7%) practice settings. Both Masters (62%) and Doctoral prepared (38%) CRNAs participated. Their experience in performing fluoroscopic guided LESIs ranged from 1 to 17 years and 50 to 12,000 procedures. Rate of occurrence for each complication was below 1%. Participants had higher rates of bruising and vasovagal reactions than other complications. No paralysis or death occurred. Neither practice setting nor experience level was related to complication rates. Participants expressed interest in participating in additional studies of complication rates. CRNAs were able to safely and effectively perform fluoroscopic guided LESIs with complication rates similar to physician rates cited in the literature. Additional study of definitions of complications and CRNA complication rates for other pain management procedures is recommended.


Cardiovascular effects of insulin sensitizers in diabetes.
Diabetic patients have a greatly increased relative risk of cardiovascular disease compared with patients without diabetes. Type 2 diabetes is caused by a combination of insulin resistance and impaired pancreatic secretion. Thiazolidinediones are a relatively new class of compounds for the treatment of type 2 diabetes mellitus that lower glucose levels by decreasing insulin resistance and glucose production by the liver. The cardiovascular benefits of thiazolidinediones include an increase in high-density lipoprotein, reduction in blood pressure, improvement in endothelial function, attenuation of markers of inflammation and reduction in albuminuria. Ongoing clinical trials are underway investigating the role of thiazolidinediones in the prevention of type 2 diabetes mellitus.


Phytoecdysteroids and vitamin D analogues--similarities in structure and mode of action.
Phytoecdysteroids are plant steroids with identical or analogue structures to the molting hormone in arthropods. The ecdysteroids exert several beneficial effects on mammals, from which the most cited and deeply examined one is the increase of muscle size and strength. This shows similarities with the mode of action of the androgenic steroids but the ecdysteroids do not bind to the cytoplasmic/nuclear receptor of the mammalian steroids. These findings led to the hypothesis that ecdysteroids possibly bind to membrane bound receptors and they are likely to influence signal transduction pathways. Probably because of their closely related chemical structures, ecdysteroids exert some similar effects in vertebrates to those of the hormone 1 alpha,25-dihydroxyvitamin D3 (1,25D) which is produced in the kidney from 25-hydroxyvitamin D3, after being converted in the liver from Vitamin D3. 1,25D generates biological responses via both genomic and rapid, nongenomic mechanisms. Structure-activity relationship studies with different Vitamin D analogues could open the possibility to show that the two ways of action (genomic and nongenomic) can be influenced separately. The connection between the Vitamin D status and muscle function is already well-described in clinical studies, and several efforts have been made to evaluate the effect of Vitamin D deficiency or supplementation on muscle morphological changes and the underlying molecular mechanisms. This paper aims to summarize the main structural commonalities between the ecdysteroids, 1,25D and other Vitamin D analogues. The similarities in their effects and pathways that might be involved in the mechanism of action of these compounds will also be discussed.


Prevalence of Oral Submucous Fibrosis, Its Correlation of Clinical Grading to Various Habit Factors among Patients of Bihar: A Cross Sectional Study.
To find out the prevalence of OSMF and its Co-relation of clinical grading to various habit factors (time span of habit practiced in years, repetition of habit practiced per day, time of habit practiced in minutes per use). This descriptive, cross-sectional survey was carried out and close ended questionnaire was used for data collection. Demographic details like gender & age and different tissue exploiting habits like, chewing gutkha, chewing areca nut, chewing panmasala with or without tobacco, plain tobacco, mawa, smoking, alcohol was recorded. Also, duration of habit in years, repetition of habit per day, time of habit per use & site of involvement was recorded. Among 5297 patients examined at OPD, 120 were diagnosed with OSMF. The present study found no statistical relation between age, gender & OSMF. The present study concluded that majority 83 (69.17%) of the OSMF patients are guthka user and buccal mucosa was most affected site. OSMF was more prevalent in patients who practiced the habit for more than 15 years. Among the OSMF patients, guthka was most commonly practiced & buccal mucosa was most commonly involved. Duration and frequency of consumption were significantly associated with severity of OSMF.


Forensic DNA phenotyping: Developing a model privacy impact assessment.
Forensic scientists around the world are adopting new technology platforms capable of efficiently analysing a larger proportion of the human genome. Undertaking this analysis could provide significant operational benefits, particularly in giving investigators more information about the donor of genetic material, a particularly useful investigative lead. Such information could include predicting externally visible characteristics such as eye and hair colour, as well as biogeographical ancestry. This article looks at the adoption of this new technology from a privacy perspective, using this to inform and critique the application of a Privacy Impact Assessment to this emerging technology. Noting the benefits and limitations, the article develops a number of themes that would influence a model Privacy Impact Assessment as a contextual framework for forensic laboratories and law enforcement agencies considering implementing forensic DNA phenotyping for operational use.


Relation between cardiovascular risk factors at adult age, and physical activity during youth and adulthood: the Leuven Longitudinal Study on Lifestyle, Fitness and Health.
This study investigated the relationship between sports participation/physical activity during youth (13 - 18 years of age) and adulthood (30 - 40 years of age), and cardiovascular risk factors (body fat and fat distribution, blood pressure, lipoprotein levels and cardiorespiratory fitness) at 40 years of age. Subjects were 166 Flemish males from "The Leuven Longitudinal Study on Lifestyle, Fitness and Health". Physical activity was assessed by means of a sports participation inventory and the Tecumseh community Health Study Questionnaire. In addition to correlation and multiple stepwise regression analyses, different groups (at risk, not at risk) were contrasted on sports participation/physical activity parameters using ANOVA. Long-term exposure during adulthood to daily physical activity was slightly related to a low/high risk profile for waist circumference, percent body fatness, triglycerides and peak VO(2). Sports participation during adolescence was not related to levels of cardiovascular risk factors at 40 years of age.