Patella fractures treated with cannulated lag screws and fiberwire® have a high union rate and low rate of implant removal.
The purpose of this study is to report the results of open reduction internal fixation of patella fractures (OTA 34 A-C) using cannulated lag screws and FiberWire® (Arthrex, Naples, FL, USA) with regard to union and symptomatic implant removal. Retrospective review of prospectively collected database. Urban Level 1 trauma center and Level 2 trauma center METHODS: All displaced intra-articular patella fractures (OTA 34 A-C) treated with ORIF by cannulated lag screws and FiberWire® tension band/cerclage between January 1, 2009 and August 1, 2018. Three hundred and eighty seven consecutive patients were identified. Fifty fractures were included in the final analysis. All patients were followed to clinical and radiographic union. Nonunion was defined as lack of clinical and radiographic union, fracture displacement, and/or return to OR for revision surgery. Rate of symptomatic implant removal was recorded. Average age was 57.7 years (range 21-86). Average follow up was 20.6 months (range 6-98 months). Average time to clinical and radiographic union was 3.1 months (range 3-7 months). Four fractures were open. There was a 96% (48/50) rate of primary union, with one patients requiring revision surgery to achieve union, and one developing an asymptomatic radiographic nonunion. The rate of symptomatic implant removal was 8% (4/50). Only 1 of the 4 was operated for a prominent suture knot, and the remaining 3 were for prominent screw removal. Knee range of motion averaged 0.37° extension to 119° flexion (range, 0-150°). Patella fractures can be treated with cannulated lag screws and FiberWire® with a high rate of primary union (96%) and a low rate of symptomatic implant removal (8%). The implant removal rate compares favorably with alternative constructs, with an equivalent rate of fracture union.


Pregnancy status and thyroid function in semi-intensive-kept Marecha she-camels (Camelus dromedarius): managerial implications.
Pakistani Marecha dromedaries, a distinctive breed not covered in the empirical data of the literature reviewed existing for thyroidal physiology in camels, are subjected to investigate thyroid function in pregnant multiparous (n = 22) and non-pregnant nor lactating (n = 22) females. The function of the thyroid gland in pubescent she-camels has evoked discrepancies among researchers exploring this topic in different breeds evolving in divergent environments. Despite season, age, sex, reproductive status, health disorders, and stress are reported as potential modulating factors, these research studies failed to find statistically significant results supporting their hypothesis. For the current research, serum samples were obtained twice a week during one month from semi-intensive-kept Marecha she-camels and analyzed for triiodothyronine (T3) and thyroxine (T4) concentrations. Feed ingredients and additives were quality assessed to examine their nutrient profile, with special attention to protein content and exogenous calcium administration. Statistical differences in serum thyroid hormone levels were found between gravid and non-gravid females, being pregnant she-camels the subgroup with higher levels (P < 0.05). The genetic background of such phenotypic variability in thyroid metabolism in camels has to be further addressed to adapt husbandry practices for breed-specific requirements. Meanwhile, local management strategies are susceptible of accurate routines for sustainable farming.


Agent-based modeling: a new approach for theory building in social psychology.
Most social and psychological phenomena occur not as the result of isolated decisions by individuals but rather as the result of repeated interactions between multiple individuals over time. Yet the theory-building and modeling techniques most commonly used in social psychology are less than ideal for understanding such dynamic and interactive processes. This article describes an alternative approach to theory building, agent-based modeling (ABM), which involves simulation of large numbers of autonomous agents that interact with each other and with a simulated environment and the observation of emergent patterns from their interactions. The authors believe that the ABM approach is better able than prevailing approaches in the field, variable-based modeling (VBM) techniques such as causal modeling, to capture types of complex, dynamic, interactive processes so important in the social world. The article elaborates several important contrasts between ABM and VBM and offers specific recommendations for learning more and applying the ABM approach.


U-insertion/deletion RNA editing multiprotein complexes and mitochondrial ribosomes in Leishmania tarentolae are located in antipodal nodes adjacent to the kinetoplast DNA.
We studied the intramitochondrial localization of several multiprotein complexes involved in U-insertion/deletion RNA editing in trypanosome mitochondria. The editing complexes are located in one or two antipodal nodes adjacent to the kinetoplast DNA (kDNA) disk, which are distinct from but associated with the minicircle catenation nodes. In some cases the proteins are in a bilateral sheet configuration. We also found that mitoribosomes have a nodal configuration. This type of organization is consistent with evidence for protein and RNA interactions of multiple editing complexes to form an ~40S editosome and also an interaction of editosomes with mitochondrial ribosomes.


[Purification of recombinant hEGF expressed in yeast Pichia pastoris and the study on its characters].
To obtain recombinant human epidermal growth factor(hEGF) that can be used in animal experiments and clinical trial. Chemically synthesized hEGF gene was expressed in Yeast Pichia pastoris and the secretory hEGF was purified by Phenysepharose 6 Fast Flow(high sub), Q-sepharose High Performance, and Superdex 30 chromatography, and its characters were studied by respective methods. The purified hEGF doesn't contain pyrogen, endotoxin, or yeast chromosome DNA and the purity reached 98%. The recombinant human EGF has correct molecular weight, pI, N-terminal amino acids sequences, peptide map, ultraviolet spectrum and well-biological activity. The purified hEGF is in accord with the requirements for animal experiments and clinical trial which provides the basis of preparing EGF agents for clinical test.


Volume Transition and Phase Coexistence in Polyelectrolyte Gels Interacting with Amphiphiles and Proteins.
Polyelectrolyte gels have the capacity to absorb large amounts of multivalent species of opposite charge from aqueous solutions of low ionic strength, and release them at elevated ionic strengths. The reversibility offers the possibility to switch between "storage" and "release" modes, useful in applications such as drug delivery. The review focuses on systems where so-called volume phase transitions (VPT) of the gel network take place upon the absorption and release of proteins and self-assembling amphiphiles. We discuss the background in terms of thermodynamic driving forces behind complex formation in oppositely charged mixtures, the role played by cross-links in covalent gels, and general aspects of phase coexistence in networks in relation to Gibbs' phase rule. We also briefly discuss a gel model frequently used in papers covered by the review. After that, we review papers dealing with collapse and swelling transitions of gels in contact with solution reservoirs of macroions and surfactants. Here we describe recent progress in our understanding of the conditions required for VPT, competing mechanisms, and hysteresis effects. We then review papers addressing equilibrium aspects of core-shell phase coexistence in gels in equilibrium. Here we first discuss early observations of phase separated gels and results showing how the phases affect each other. Then follows a review of recent theoretical and experimental studies providing evidence of thermodynamically stable core-shell phase separated states, and detailed analyses of the conditions under which they exist. Finally, we describe the results from investigations of mechanisms and kinetics of the collapse/swelling transitions induced by the loading/release of proteins, surfactants, and amphiphilic drug molecules.


Systemic differential gene regulation of the inter-α-trypsin inhibitor family in acute necrotizing pancreatitis in mice.
Therapy for systemic complications in severe necrotizing pancreatitis remains symptomatic owing to the unavailability of more specific therapeutic targets. We investigated the differential gene expression in typically affected organs in a mouse model of severe necrotizing pancreatitis. Acute necrotizing pancreatitis was induced in mice by retrograde infusion of taurocholate into the common bile duct. Microarray hybridization was subsequently performed with mRNA isolated from the spleen, liver, intestine, and lungs. Additionally, quantitative real-time polymerase chain reaction was performed to confirm the microarray results. Severe necrotizing pancreatitis induced widespread changes in gene expression, affecting 27.20% of the genes tested in the spleen and 29.07% in the liver. Fewer genes were differentially regulated in the intestine (10.28%) and the lungs (10.75%). Only 10 genes were found to be upregulated in all 4 organs using microarray analysis. This upregulation in all organs was confirmed by quantitative real-time polymerase chain reaction for only 3 molecules. These molecules were lipocalin 2, insulin-like growth factor binding protein 1, and CD14. Additionally we observed significantly aberrant gene regulation of inter-α-trypsin inhibitor family members in several organs. Differential gene regulation in severe necrotizing pancreatitis is far more organ specific than anticipated, with only 3 molecules uniformly regulated systemically. The inter-α-trypsin inhibitor family of molecules appears to play a crucial biologic role in the systemic inflammatory response in acute pancreatitis. Finally, owing to its regulation and function, α1-microglobulin (or bikunin) may be a suitable predictive marker of the systemic inflammatory response syndrome in acute pancreatitis.


Percutaneous drainage and stenting for palliation of malignant bile duct obstruction.
Percutaneous biliary drainage and stenting (PTBD) for palliation of malignant obstructive jaundice has evolved to a safe and effective technique. PTBD is equally effective for treatment of distal and proximal bile obstruction. Metal self-expandable stents have proved superior to plastic stents and should therefore be used. Technical success is >90% en clinical success is >75% in all major series. There are a considerable number of complications, but most can be treated conservatively and procedure-related mortality is <2% in most series. Thirty-day mortality after PTBD is >10% in many series, but this is largely due to the underlying disease. About 10-30% of patients will have recurrent jaundice at some point in their disease after PTBD and require re-intervention.


Hyper-Rayleigh scattering of protein-modified gold nanoparticles.
The nonlinear optical properties of protein-modified gold nanoparticles has been studied by the hyper-Rayleigh scattering (HRS) technique. HRS signals from the nanoparticles coated with goat-anti-human IgG have been obtained when pumped with a laser pulse with a wavelength of 1064 nm. The HRS signals of gold nanoparticles with IgG were larger than those of bare gold nanoparticles. This can be explained by a noncentrosymmetric effect. It was also found that the HRS signals from the IgG-coated gold nanoparticles could be greatly increased when the antigen was added due to gold nanoparticle aggregation. Our experiment found that the HRS method could produce a measurable signal with 10 microg/ml antigen added, while the colorimetric method using UV spectrum detection required 100 microg/ml of added antigen. The results show that the HRS measurement of immunogold nanoparticles could become a potential immunoassay in determining small levels of antigen in aqueous samples.


When the aortoiliac bifucation is occluded:Leriche syndrome.
Leriche syndrome is a special type of obliterating arterial disease of the lower limbs which results in thrombotic occlusion of the aortoiliac junction. We report the case of a 65-year-old patient with known cardiovascular and nephrological pathological history, who presented with acute abdominal pain with intermittent claudication of the lower limbs and in whom clinical examination found abolition of the femoral pulses. Doppler ultrasound of the abdominal aorta revealed aortic thrombosis in the lower of the renal segment extended to the iliac bifurcation with damping of upstream circulatory speeds. We supplemented with a CT angiography of the aorta and lower limbs which demonstrated extensive arterial thrombosis from the abdominal aorta to the bilateral external iliac arteries.


A novel injury site-natural antibody targeted complement inhibitor protects against lung transplant injury.
Complement is known to play a role in ischemia and reperfusion injury (IRI). A general paradigm is that complement is activated by self-reactive natural IgM antibodies (nAbs), after they engage postischemic neoepitopes. However, a role for nAbs in lung transplantation (LTx) has not been explored. Using mouse models of LTx, we investigated the role of two postischemic neoepitopes, modified annexin IV (B4) and a subset of phospholipids (C2), in LTx. Antibody deficient Rag1-/- recipient mice were protected from LTx IRI. Reconstitution with either B4 or C2nAb restored IRI, with C2 significantly more effective than B4 nAb. Based on these information, we developed/characterized a novel complement inhibitor composed of single-chain antibody (scFv) derived from the C2 nAb linked to Crry (C2scFv-Crry), a murine inhibitor of C3 activation. Using an allogeneic LTx, in which recipients contain a full nAb repertoire, C2scFv-Crry targeted to the LTx, inhibited IRI, and delayed acute rejection. Finally, we demonstrate the expression of the C2 neoepitope in human donor lungs, highlighting the translational potential of this approach.


Quantification of Urbanization Using Night-Time Light Intensity in Relation to Women's Overnutrition in Bangladesh.
Urbanization is accelerating in developing countries, which are simultaneously experiencing a rise in the prevalence of overnutrition (i.e., overweight and obesity), specifically among women. Since urbanization is a dynamic process, a continuous measure may better represent it when examining its association with overnutrition. However, most previous research has used a rural-urban dichotomy-based urbanization measure. This study utilized satellite-based night-time light intensity (NTLI) data to measure urbanization and evaluate its association with body weight in reproductive-aged (15-49) women in Bangladesh. Multilevel models estimated the association between residential area NTLI and women's body mass index (BMI) or overnutrition status using data from the latest Bangladesh Demographic and Health Survey (BDHS 2017-18). Higher area-level NTLI was associated with a higher BMI and increased odds of being overweight and obese in women. Living in areas with moderate NTL intensities was not linked with women's BMI measures, whereas living in areas with high NTL intensities was associated with a higher BMI or higher odds of being overweight and obese. The predictive nature of NTLI suggests that it could be used to study the relationship between urbanization and overnutrition prevalence in Bangladesh, though more longitudinal research is needed. This research emphasizes the necessity for preventive efforts to offset the expected public health implications of urbanization.


Treatment outcomes of Veteran men in a comprehensive dialectical behavior therapy program: Characterizing sex differences in symptom trajectories.
Dialectical Behavior Therapy (DBT) is one of the primary psychosocial treatments for reducing suicidal behaviors and improving psychosocial outcomes among patients with borderline personality disorder (BPD) and has been shown to reduce BPD symptoms when delivered in a Veteran Affairs medical center setting. Despite evidence of similar rates of BPD in both men and women, the vast majority of treatment outcome research in BPD has focused on women. We sought to characterize sex differences in symptom trajectories among Veterans participating in a comprehensive DBT program. We found that Veteran men and women who entered the DBT program were diagnostically and demographically similar. Participants exhibited reductions in BPD symptoms and improvements in emotion regulation over the course of treatment. Moreover, Veteran men reported BPD symptom reductions that were not statistically inferior to those of Veteran women and exhibited a sharper reduction in these symptoms. This research provides support for the use of DBT as a psychosocial treatment for Veteran men with BPD symptoms.


Effects of interleukin-4 on the formation of macrophages and osteoclast-like cells.
The lymphokine interleukin-4 (IL-4) is an important lymphocyte growth factor, and it also has a modulatory role on hematopoiesis. It was recently reported that IL-4 has an inhibitory effect on bone resorption in vitro, but the underlying mechanisms are not well known. We studied its effects on the formation of osteoclast-like cells in mouse bone marrow cultures and in cocultures of spleen cells and stromal cells. The addition of recombinant mouse IL-4 (0.01-10 ng/ml) induced a marked dose-dependent inhibition on the formation of TRAP-positive multinucleated cells (MNC) in bone marrow cultures. The effect was blocked by anti-IL-4 antibodies and was not related to a decreased production of IL-6. The inhibitory effect required the presence of IL-4 during the second half of the culture period. Time course experiments showed that IL-4 impaired the formation of osteoclast-like cells rather than inducing the disappearance of previously formed cells. This inhibitory effect was associated with increased numbers of esterase-positive cells. Moderately high doses of IL-4 (1-10 ng/ml) also induced the formation of abundant macrophage polykaryons that did not form resorption pits. IL-4 had a similar inhibitory effect on the formation of osteoclast-like cells in cocultures of mouse spleen cells and stromal cells. Our results suggest that IL-4 acts on uncommitted macrophage-osteoclast precursors, inducing a preferential differentiation toward the macrophage lineage and thus decreasing the formation of osteoclast-like cells.


Simultaneous knock-down of Bcl-xL and Mcl-1 induces apoptosis through Bax activation in pancreatic cancer cells.
Anti-apoptotic Bcl-2 family proteins have been reported to play an important role in apoptotic cell death of human malignancies. The aim of this study was to delineate the mechanism of anti-apoptotic Bcl-2 family proteins in pancreatic cancer (PaCa) cell survival. We first analyzed the endogenous expression and subcellular localization of anti-apoptotic Bcl-2 family proteins in six PaCa cell lines by Western blot. To delineate the functional role of Bcl-2 family proteins, siRNA-mediated knock-down of protein expression was used. Apoptosis was measured by Cell Death ELISA and Hoechst 33258 staining. In the results, the expression of anti-apoptotic Bcl-2 family proteins varied between PaCa cell lines. Mcl-1 knock-down resulted in marked cleavage of PARP and induction of apoptosis. Down-regulation of Bcl-2 or Bcl-xL had a much weaker effect. Simultaneous knock-down of Bcl-xL and Mcl-1 strongly induced apoptosis, but simultaneous knock-down of Bcl-xL/Bcl-2 or Mcl-1/Bcl-2 had no additive effect. The apoptosis-inducing effect of simultaneous knock-down of Bcl-xL and Mcl-1 was associated with translocation of Bax from the cytosol to the mitochondrial membrane, cytochrome c release, and caspase activation. These results demonstrated that Bcl-xL and Mcl-1 play an important role in pancreatic cancer cell survival. Targeting both Bcl-xL and Mcl-1 may be an intriguing therapeutic strategy in PaCa.


Deciphering durable resistance one R gene at a time.
Characterizations of durable resistance genes in crop plants are coming to the fore. A new study characterizing the wheat gene Lr67 shows that how a plant manages sugar transport affects the ability of a broad group of fungal pathogens to colonize their host.


Cell biology of human ovarian surface epithelial cells and ovarian carcinogenesis.
Most epithelial ovarian carcinomas have been suggested to arise from the ovarian surface epithelium, which covers an ovary as a layer of flat to cuboidal cells. The epithelium is physiologically involved in follicular rupture and the subsequent repair of the follicle wall during reproductive age. Invagination and inclusion cysts are formed in the cortical stroma after cyclic ovulation. Consequently, ovulation may cause a loss of integrity of the surface epithelium followed by stepwise sequence of genetic alteration. Inclusion cysts are actually more common in ovaries contralateral to those containing malignant epithelial tumors than in control ovaries. Human ovarian surface epithelial cells exhibit a gland formation in coculture with endometrial stromal cells in an estrogen-rich environment. The phenotypic plasticity of these cells shares a mesenchymal property when they are cultured on two layers of extracellular matrix and collagen gel. As an in vitro study of ovarian carcinogensis, several neoplastic cell lines were recently established from the surface epithelial cells of the human ovary. SV 40 large T-antigen transfection into the epithelial cells induced some immortalized cell lines, one of which showed anchorage-independent growth and tumor formation in athymic mice. The tumors were histologically undifferentiated carcinoma. These cell lines may lead to insights into the preneoplastic and early stages of epithelial ovarian carcinomas. To understand the pathogenesis of epithelial ovarian cancer, specifically designed studies of ovarian surface epithelium and the related structural changes encountered after ovulation and these existing in ovarian carcinomas are required.


Virus C genotype predisposes to primary hypothyroidism during interferon-α treatment for chronic hepatitis C.
The treatment of the chronic hepatitis C (HCV) with α-interferon is associated with thyroid dysfunction (TD). The aim of this study was to evaluate thyroid function outcome among patients with chronic HCV under treatment with conventional interferon (IFN) or peguilated interferon (PEG-IFN) in association with ribavirin. We studied 293 patients with chronic HCV, submitted to drug therapy for 24 or 48 weeks. Initially, we evaluated FT4, TSH, TPOAb, TgAb, and continued to monitor FT4 and TSH every three months during therapy and six months thereafter. At baseline, TD prevalence was 6.82% (n = 20); 6.14% hypothyroidism; 0.68% hyperthyroidism. TPOAb was present in 5.46% of euthyroid patients. Out of 273 euthyroid patients at baseline, 19% developed TD: 17.2% hypothyroidism; 1.8% hyperthyroidism; 5.1% destructive thyroiditis (DT). 90% of TPOAb-positive patients at baseline developed hypothyroidism vs 14.5% of TPOAb-negative patients (p < 0.001). On average, TD occurred after 25.8 ± 15.5 weeks of treatment. 87.2% of patients who developed hypothyroidism did so during the first therapeutic cycle (p = 0.004; OR = 3.52; 95% CI = 1.36-9.65). Patients infected with genotype 1 virus were 2.13 times more likely to develop hypothyroidism (p = 0.036; 95% CI = 1.04-4.38). Hypothyroid and DT patients presented higher TSH levels before-treatment than patients who had remained euthyroid (p < 0.001; p = 0.002, respectively). DT patients presented lower qALT (p = 0.012) than euthyroid patients. Hypothyroidism was the most frequent TD, especially during the first cycle of α-interferon. Genotype 1 virus was associated with a risk two times higher for developing the illness. There was no need to interrupt or to change HCV treatment. Therefore, approximately 34% of TD was transient.


Influence of background particulate matter (PM) on urban air quality in the Pacific Northwest.
Elevated particulate matter concentrations due to Asian long-range transport (LRT) are frequently observed in the free troposphere (FT) above the Pacific Northwest, U.S. Transport of this aerosol from the FT to the boundary layer (BL) and its effect to local air quality remain poorly constrained. We used data collected at the Mount Bachelor observatory (MBO, 2.8 km a.s.l) and from ground stations in the Pacific Northwest to study transport of fine particulate matter (PM) from the FT to the BL. During Asian LRT episodes PM concentrations were clearly elevated above the corresponding monthly averages at MBO as well as at low elevation sites across Washington and Oregon. Also, a clear correlation between MBO and low elevation sites was observed, indicating that LRT episodes are seen in both the FT and BL. In addition, drum impactor measurements show that the chemical composition of PM at MBO was similar to that measured at the BL sites. Using a simple regression model, we estimate that during springtime, when the transport from Asia is most effective, the contribution of Asian sources to PM2.5 in clean background areas of the Pacific Northwest was on average 1.7 μg m(-3) (representing approximately 50-80% of PM). The influence of LRT PM was also seen in measurement stations situated in the urban and urban background areas. However, the fraction of LRT PM was less pronounced (36-50% of PM) due to larger local emissions in the urban areas.


The nucleolus: an organelle formed by the act of building a ribosome.
Recent evidence corroborates the idea that the structure of the nucleolus need not be strictly maintained for proper function, suggesting that the organelle is composed of supramolecular assemblies formed during rRNA synthesis. More controversial is whether the nucleolus exists in the absence of rRNA synthesis and whether it interacts with the nuclear scaffold. The simultaneous and highly integrative nature of building a ribosome is reflected in the numerous observations showing that proteins involved in all aspects of ribosomal biogenesis affect pre-rRNA processing. The identification of several new nucleolar proteins without an obvious role in pre-rRNA metabolism may provide the field with long sought after assembly factors that might be key players in eukaryotic ribosome biogenesis.


Effect of order of exercise intensity upon cardiorespiratory, metabolic, and perceptual responses during exercise of mixed intensity.
Exercise of mixed intensities can be of benefit in many different ways. However, whether physiological interaction exists between exercises of different intensity is questionable. As such, the primary aim of this study was to examine the effect of order of exercise intensity upon cardiorespiratory, metabolic, and perceptual responses during exercise of mixed intensity. Eight males and four females volunteered to serve as subjects for the study. They were informed of the purpose of the experiment and gave their written consent to participate. Each subject completed a peak oxygen uptake ( VO(2peak)) test and two submaximal exercises of mixed intensity on three separate laboratory visits. During each submaximal exercise trial, subjects performed a 15-min (high intensity) exercise at 70% VO(2peak) that was followed by another 15-min (low intensity) exercise at 50% VO(2peak) (high/low, H/L), or a 15-min exercise at 50% VO(2peak) that was followed by another 15-min exercise at 70% VO(2peak) (low/high, L/H). Oxygen uptake ( VO(2)), respiratory exchange ratio ( R), expired ventilation ( V(E)), heart rate (HR) and ratings of perceived exertion (RPE) were measured every 5 min throughout exercise. Energy expenditure and carbohydrate and fat oxidation were calculated from VO(2) adjusted for substrate metabolism using R and then accumulated for each phase of exercise intensity as well as for the entire exercise session. VO(2) and HR were higher ( P<0.05), while R was lower ( P<0.05) at the lower intensity in H/L than in L/H. V(E) and RPE were lower ( P<0.05) at the higher intensity in H/L than in L/H. While no differences in caloric expenditure and carbohydrate oxidation between the two trials were observed, fat oxidation was higher ( P<0.05) both at the lower intensity and for the entire trial in H/L than in L/H. It appears that during exercise of mixed intensity, placing some periods of moderate intensity exercise prior to a milder one is a more favorable sequence in that it can elicit a greater fat oxidation while being felt less stressful.


The Clinical Significance of Lumbosacral Transitional Vertebrae on the Surgical Outcomes of Lumbar Discectomy: A Retrospective Cohort Study of Young Adults.
To evaluate whether the presence of lumbosacral transitional vertebrae (LSTV) affects the clinical outcomes of microdiscectomy (MD) in young adults with lumbar disc herniation. We retrospectively included 398 patients who were followed-up for at least 2 years after MD for lumbar disc herniation at L4/5 (disc above the LSTV). The patients were divided into 2 groups. Group A was made up of 31 patients in whom LSTV was detected. Group B, in contrast, was made up of 35 patients in whom LSTV was not detected. The LSTV were classified using plain radiographs and three-dimensional computed tomography by Castellvi et al. The primary outcome measure was pain intensity at each follow-up visit assessed with visual analog scale for back and leg. Secondary outcome measures included the Oswestry Disability Index, a 12-item short-form health survey for quality of life, complications, and recurrence rate. After surgery, the visual analog scale scores for the back and leg decreased significantly in both groups. However, the back pain intensity in group A worsened at 12 and 24 months postoperatively. The Oswestry Disability Index scores and 12-item short-form health survey (both mental and physical) worsened at 12 and 24 months postoperatively in group A. Two cases of reherniation (6.5 %) were observed in group A, who required reoperation. LSTV can limit a patient's clinical improvement after MD with regard to pain intensity and recurrence. Caution must be taken when a patient is scheduled to undergo surgery.


Short-term dual antiplatelet therapy (DAPT) followed by P2Y12 monotherapy versus traditional DAPT in patients undergoing percutaneous coronary intervention: meta-analysis and viewpoint.
The optimal duration dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) is subject to debate. A short-duration DAPT (one month to three months) followed by P2Y12 monotherapy instead of standard 6 to 12 months DAPT followed by aspirin monotherapy after PCI has been suggested. We meta-analyzed studies comparing short-term (≤ 3 months) DAPT followed by P2Y12 monotherapy versus standard DAPT in patients after PCI. In total, 2304 studies were screened at title and abstract level. The primary endpoint was major bleeding. Secondary endpoints included myocardial infarction, stent thrombosis, stroke, and all-cause mortality. Study level data were analyzed. Heterogeneity was assessed using the I2 statistic. Risk rates (RR) were calculated using a random-effects model (DerSimonian and Laird) for clinical outcomes for each individual study and consecutive pooling. In total, 21970 patients from three studies were analyzed. Between P2Y12 inhibitor monotherapy versus DAPT, there were similar rates of major bleeding (RR 0.67 95%CI 0.34-1.32; p = 0.25; I2 75%), mortality (RR 0.92 95%CI 0.78-1.09; p = 0.33; I2 0%) and stroke (RR 0.97 95%CI 0.52 - 0.18; p = 0.92; I2 57%). Endpoints assessing thrombotic events showed no statistically significant difference including myocardial infarction (RR 0.99 95%CI 0.85-1.15; p = 0.86; I2 0%) and stent thrombosis (RR 1.03 95%CI 0.74-1.44; p = 0.87; I2 0%). The experimental treatment with P2Y12 monotherapy after very short-term DAPT was not superior to standard DAPT. Our meta-analysis adds insight that DAPT might be safely shortened in selected patient strategies. However, DAPT remains the gold standard for antithrombotic treatment after PCI.


Human papillomavirus type 16 (HPV 16) gene expression and DNA replication in cervical neoplasia: analysis by in situ hybridization.
We have analyzed human papillomavirus (HPV) type 16 RNA expression in premalignant cervical lesions of different severity and in squamous cervical cancers by RNA-RNA in situ hybridization in order to find differences in the topographic distribution of viral RNA, which might correlate with the severity of disease. In the basal layer of low-grade squamous intraepithelial lesions (SIL) only weak transcription of viral early genes was observed. Signal intensity increased strongly in the more differentiated cells accompanied by high levels of HPV DNA replication. This pattern of viral gene expression, together with the onset of viral late transcription in the upper differentiated layer of the epithelium, most likely reflects the productive phase of viral infection. In contrast, in high-grade SIL viral transcription was comparatively strong in basal cells and evenly distributed throughout the undifferentiated epithelium. This difference of viral transcription in the basal layer of the respective lesions points to an altered regulation of viral gene expression which may be causally linked to the progression of precursor lesions. Evidence for disrupted expression of 3' early genes (E2, E4, and E5), analogous to the situation in HPV-DNA containing cervical carcinoma-derived cell lines, was not found in any of the HPV-16-positive premalignant lesions nor in the majority of cancers. The similarity of the viral transcription pattern of high-grade SIL and cancers suggests that additional host gene alterations are necessary for malignant progression.


HSP70-1 is required for interleukin-5-induced angiogenic responses through eNOS pathway.
We report a pivotal role for IL-5 as an angiogenic activator. IL-5 increased proliferation, migration and colony tube formation in HUVECs associated with the phosphorylation of ERK and AKT/eNOS, and promoted microvessel sprouting from an angiogenesis animal model. The angiogenic effects were confirmed in IL-5-deficient mice and addition of IL-5 antibody. HSP70-1 was identified via expression profiling following IL-5 stimulation. A siRNA knockdown of HSP70-1 suppressed angiogenic responses and eNOS phosphorylation induced by IL-5. HSP70-1 overexpression enhanced IL-5-induced angiogenic responses. In addition, IL-5-induced neo-vascular formation was verified in both HSP70-1 knockout and HSP70-1 transgenic mice. Furthermore, transcription factor AP-1 was a main factor in IL-5-induced HSP70-1 in response to ERK and AKT signaling pathway. Angiogenic responses induced by VEGF had no effect in either HSP70-1 siRNA in vitro or HSP70-1 knockout mice. IL-5-induced angiogenic responses depended on the binding of IL-5Rα. Our data demonstrate that binding of IL-5 to IL-5Rα receptors enhances angiogenic responses by stimulating the expression of HSP70-1 via the eNOS signaling pathway.


Improvement in knowledge, social cognitive theory variables, and movement through stages of change after a community-based diabetes education program.
The objective of this program was to demonstrate the impact of a community-based diabetes education program. Participants were adults (N=239; mean age+/-standard deviation=63+/-10 years) with diabetes or caretakers. Community-based education incorporating Social Cognitive Theory and Stages of Change Theory included three group sessions focused on meal planning with cooking demonstrations. Knowledge and Social Cognitive Theory/Stages of Change variables were assessed pre- and postintervention. At posttest, significantly more (P<.05) used herbs in place of salt, cooked with olive or canola oils, used artificial sweeteners in baking (Stages of Change Theory), and were confident to change their diet and to prepare healthful meals. Knowledge of diabetes and nutrition increased (P<.05) and was a factor in postintervention belief in ability to use food labels and that meal planning was helpful. This community-based diabetes education intervention resulted in positive impacts on knowledge, health beliefs, and self-reported behaviors. Improvement in knowledge can be instrumental in moving individuals to an action or maintenance stage and in improving self-efficacy.


Effects of spinal anaesthesia and intravenous general anaesthesia on the absorption of normal salinein patients undergoing hysteroscopic endometrial resection: an observational study.
The absorption of uterine distention fluid during hysteroscopic endometrial resection can cause volumeoverload, which can lead to coagulation dysfunction, acute left heart failure and pulmonary oedema in patients. The effects of spinal anaesthesia and intravenous general anaesthesia on the absorption of normal saline as uterine distention fluid during hysteroscopic surgery remain unclear. The aim of this clinical trial was toobserve the effects of spinal anaesthesia and intravenous general anaesthesia on the absorption of normal saline in patients undergoing hysteroscopic endometrial resection. A total of 126 patients undergoing elective hysteroscopic endometrial resection were divided into a spinal anaesthesia group (s group) and a propofol-fentanyl intravenous anaesthesia group (PF group), with 63 cases in each group, and both groups were divided into a short-term group (S1 group and PF1 group) and a long-term group (S2 group and PF2 group) according to the operation time. The primary outcome was the absorption of normal saline, and the secondary outcomes included the perioperative SBP, DBP, HR and SpO2 and postoperative haematocrit values, and the incidence of postoperative complications. The volume of saline absorbed was significantly increased in the S2 and PF2 groups compared with the S1 and PF1 groups (P < 0.001). There was a significant positive correlation between the amount of normal saline absorbed and the operation time (r = 0.895, P < 0.001). The postoperative haematocrit value was slightly lower than that before the operation in all four groups (P < 0.05), and there were no differences in the incidences of urinary retention, sinus bradycardia or hypotension between groups (P > 0.05). There was no difference in the effects of spinal anaesthesia and intravenous general anaesthesia on the absorption of normal saline during hysteroscopic endometrial resection, and the absorption of normal saline increased accordingly with the extension of operation time.


Whole blood serotonin and plasma tryptophan using high-pressure liquid chromatography with electrochemical detection.
Methods are detailed for whole blood serotonin (5-HT), equivalent to platelet 5-HT, and plasma tryptophan. These assays may be carried out on the same blood sample which need be no more than 1 ml, are rapid, and avoid the difficulties, such as protein precipitation and fluorophor formation, encountered in other methods. The linearity of the methods is extensive and allows for accurate measurement of low concentrations. Data are given for normal humans and for patients receiving psychiatric treatment for depression.


Enzymatic and nonenzymatic lipid peroxidation capacities and antioxidants in hypoxic and reoxygenated rat myocardium.
The effects of 60 min hypoxia and subsequent reoxygenation for 30 min on enzymatic (NADPH-dependent) and nonenzymatic (Fe2+/ascorbate-induced) lipid peroxidation capacities and on antioxidant levels were studied using Langendorff-perfused rat hearts. The assays were done on the myolayer of the right ventricle (RV) and on the subepi- and subendomyolayers of the left ventricle (epi/endo LV) after normoxic, hypoxic, and reoxygenation phases. The region injured by hypoxia/reoxygenation was located mainly in endo LV, seen as a lesser penetration of the fluorescent dye fluorescein in the myocardium. The electron microscopic findings after reoxygenation revealed swelling of the mitochondria, amorphous mitochondrial structures, and formation of paracrystallines. The myofibrillar structure of the cells was disrupted and the cells showed marked fluid accumulation. Membrane structures were marginated and formed blebs and multilamellar bodies. Ultrastructural changes were most prominent in endo LV, especially after reoxygenation. The increase in leakage of lactate in the perfusate revealed the onset of anaerobic metabolism. Abrupt release of the cytoplasmic enzymes lactate dehydrogenase and creatine kinase at the beginning of the reoxygenation phase suggested cell membrane injury. The capacity for Fe2+/ascorbate-induced lipid peroxidation slightly increased in RV and that for NADPH-dependent, enzymatic lipid peroxidation in endo LV after reoxygenation. Catalase, glutathione peroxidase, and superoxide dismutase activities remained unchanged, whereas glucose-6-phosphate dehydrogenase activity decreased after reoxygenation in RV.(ABSTRACT TRUNCATED AT 250 WORDS)


Involvement of the mammalian target of rapamycin signaling in the antidepressant-like effect of group II metabotropic glutamate receptor antagonists.
Growing evidence has indicated that the blockade of group II metabotropic glutamate (mGlu2/3) receptor exerts antidepressant-like effects in several animal models of depression. However, the molecular mechanisms underlying the action of mGlu2/3 receptor antagonists are not well understood. Here, we investigated the involvement of mammalian target of rapamycin (mTOR) signaling in the acute and sustained antidepressant-like effects of mGlu2/3 receptor antagonists such as (1R, 2R, 3R, 5R, 6R)-2-amino-3-(3,4-dichlorobenzyloxy)-6-fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (MGS0039) and (2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid (LY341495). Mice were subjected to a tail suspension test (TST) to assess the acute and sustained antidepressant-like effects. We evaluated the effect of rapamycin, an mTOR antagonist, on the acute and sustained antidepressant-like effects of mGlu2/3 receptor antagonists. Both MGS0039 and LY341495 exerted antidepressant-like effects, as evaluated using the TST; these effects were sustained for 24 h. Pretreatment with rapamycin blocked the sustained, but not the acute, antidepressant-like effects of mGlu2/3 receptor antagonists, as observed in ketamine. The present result suggests that the blockade of the mGlu2/3 receptor may activate mTOR signaling, and that the activation of mTOR signaling may contribute to the sustained antidepressant-like effects of mGlu2/3 receptor antagonists.


Current-voltage relations of Cs+-inhibited K+ currents through the apical membrane of frog skin.
The voltage-dependence of the inhibitory effect of mucosal Cs+ on the inward K+ current through the apical membrane of frog skin (Rana temporaria) was studied by recording transepithelial current-voltage relations. Experiments were performed with skins exposed to NaCl and KCl Ringer solutions on the serosal and mucosal side respectively (control skins), as well as with tissues incubated with K2SO4 Ringer solutions on both sides (depolarized skins). Studies of the dose-dependence of the Cs+ block showed that under both experimental conditions the apparent affinity of Cs+ increased as the transepithelial potential was clamped at higher mucosal positive voltages. Under control conditions, the concentration of Cs+ required to block 50% of the K+ current (KCs) recorded while the transepithelial voltage was clamped at zero mV was 16 mmol/l. KCs decreased exponentially with mucosal positive voltages. The dependence of KCs on the membrane potential was analyzed with Eyring rate theory in which Cs+ was assumed to block the K+ transport by binding to a site within the channel. The analysis showed that this site is located at a relative electrical distance delta = 0.32 of the voltage drop across the apical membrane, measured from the cytosolic side. The Hill coefficient obtained from this analysis was n = 3.1. Experiments with K+-depolarized tissues showed that only inward K+ currents recorded with positive transepithelial voltages were depressed by external Cs+. Also under these conditions KCs showed an exponential dependence on the transepithelial potential. The analysis of these data with the rate theory revealed delta = 0.09 and n = 1.7.(ABSTRACT TRUNCATED AT 250 WORDS)


CIN Extension at Colposcopy: Relation to Treatment and Blood Parameters.
To determine the colposcopic lesion size that predicts the presence of residual lesion in patients with cervical intraepithelial neoplasia (CIN) 2/3, to aid gynaecologists in selecting conservative management. Data from 51 patients with low- and high-grade squamous intraepithelial lesions were evaluated. Colposcopic images were captured and lesion areas were calculated. Polymerase chain reaction (PCR) for human papillomavirus was performed. Laboratory parameters were evaluated. Receiver operating characteristic (ROC) curves were used to obtain cut-off values for lesion area. The performance of PCR in the detection of high-grade CIN was assessed. A flowchart was created to compare the costs of related procedures in the Brazilian health system. For CIN 2/3 treated with excisional surgery, the best cut-off value for lesion area below which no residual lesion was present was 21 019 pixels2 (58.87 mm2). The cut-off value that predicted compromised surgical margins was 155 577.65 pixels2 (435.75 mm2). Among all patients with CIN, lesion area correlated inversely with neutrophil/lymphocyte ratio (NLR; r = -0.446, P = 0.001), platelet/lymphocyte ratio (PLR; r = -0.438, P = 0.001), and absolute number of leukocytes (r = -0.351, P = 0.011). Conservative clinical management with semi-annual clinical follow-up was found to reduce direct costs to the Brazilian Health System by R $909.82 (US $169.42). CIN reflects systemic alteration, leading to altered NLRs, PLRs, and absolute numbers of leukocytes. Patients with high-grade CIN and colposcopic lesion areas <21 019 pixels2 could benefit from conservative management, which would result in cost savings for the Brazilian health system.


Secreted osteopontin from CD4+ T cells limits acute graft-versus-host disease.
Osteopontin (OPN) has been considered a potential biomarker of graft-versus-host disease (GVHD). However, the function of OPN in GVHD is still elusive. Using a mouse model of acute GVHD (aGVHD), we report that OPN generated by CD4+ T cells is sufficient to exert a beneficial effect in controlling aGVHD through limiting gastrointestinal pathology, a major target organ of aGVHD. CD4+ T cell-derived OPN works on CD44 expressed in intestinal epithelial cells (IECs) and abates cell death of IECs. OPN also modulates gut microbiota with enhanced health-associated commensal bacteria Akkermansia. Importantly, we use our in vivo mouse mutant model to specifically express OPN isoforms and demonstrate that secreted OPN (sOPN), not intracellular OPN (iOPN), is solely responsible for the protective role of OPN. This study demonstrates that sOPN generated by CD4+ T cells is potent enough to limit aGVHD.


Meta-analysis as a tool for understanding existing research literature.
This article describes the rationale for and methods used in conducting meta-analyses in rehabilitation research. Advantages and disadvantages of meta-analysis, vis a vis the narrative and quantitative literature reviews described in previous articles, are discussed. Hypothetical and actual examples from the rehabilitation and related health sciences fields are used to illustrate points throughout the text.


S-adenosyl-L-methionine synthetase and phospholipid methyltransferase are inhibited in human cirrhosis.
We have measured the activity S-adenosyl-L-methionine synthetase in liver biopsies from a group of controls (n = 17) and in 26 cirrhotics (12 alcoholic and 14 posthepatic). The activity of this enzyme was markedly reduced in the group of cirrhotics (285 +/- 32 pmoles per min per mg protein) when compared with that observed in controls (505 +/- 37 pmoles per min per mg protein). No differences in S-adenosyl-L-methionine synthetase was observed between both groups of cirrhotics. Similarly, a marked reduction in the activity phospholipid methyltransferase was also observed in liver biopsies from the same group of cirrhotics (105 +/- 12 pmoles per min per mg protein) when compared with the control subjects (241 +/- 13 pmoles per min per mg protein). Again, no difference in the activity of this enzyme was observed between both groups of cirrhotics. These results indicated a marked deficiency in the metabolism of S-adenosyl-L-methionine in cirrhosis.


Tick attachment sites.
The duration of tick attachment is related to the likelihood of disease transmission. To be able to locate and remove an attached tick is important. Sixty-seven patients presenting with tick bites to the Karadeniz Technical University emergency department and 3 different first-stage health institutions between April and July 2006 were investigated to determine the distribution of the bites. Tick attachment site distribution was determined as follows: 9% head-neck, 5% arm, 24% stomach-groin, 7% back, 18% chest-shoulder, 25% leg-foot, and 12% hip. According to the results of our study, 20% of ticks attach to regions of the body that patients cannot themselves see. After travel in endemic areas, a complete inspection of the entire body surface is required to achive early tick removal.


Factors influencing mobility in community-dwelling older adults during the early COVID-19 pandemic: a cross-sectional study.
In older adults, mobility is important for maintaining their independence and quality of life, and it influences their physical, cognitive, and social health. This study aimed to identify the physical and psychosocial factors that affected the mobility of community-dwelling older adults, aged 65 years or older, who were socially isolated during the coronavirus disease 2019 (COVID-19) pandemic due to stay-at-home policies. The participants in this study were 214 community-dwelling older adults in Korea, and a cross-sectional survey was conducted from December 2020 to January 2021. Variables included participants' general characteristics, mobility, sitting time, depression, social support, and cognitive function. Multiple linear regression analysis showed that the factors influencing older adults' mobility during the COVID-19 pandemic were depression (β=-0.29, p < .001), age (65-74 years old) (β = 0.19, p = .002), a lower level of education (β=-0.17, p = .006), two or more comorbidities (β=-0.18, p = .001), sitting time (β=-0.17, p = .004), and the ability to drive a vehicle (β = 0.14, p = .017). Home healthcare interventions are needed to limit psychosocial issues and improve mobility for older adults who had limited mobility during the COVID-19 pandemic.


Mediating effect of vascular risk factors underlying the link between gestational diabetes and cardiovascular disease.
Women with gestational diabetes (GDM) have an elevated lifetime incidence of cardiovascular disease (CVD), but the basis of this excess risk remains to be established. In this context, we hypothesized that chronic exposure to adverse cardiovascular risk factors may contribute to their elevated risk of CVD. We thus sought to quantify the determinants of CVD risk in women with a history of GDM by performing mediation analyses. Women in Ontario, Canada, with a live-birth pregnancy between Jan 1998 and Dec 2017 (n=757,541) were followed for a median of 13.2 years and stratified into the following 4 groups: women with GDM who developed CVD (GDM+/CVD+); women without GDM who developed CVD (GDM-/CVD+); those with GDM but no CVD (GDM+/CVD-); and those with neither GDM nor CVD (GDM-/CVD-). Lipids (total cholesterol, LDL, HDL, triglycerides) and glycemic variables (A1c, fasting glucose) were measured between 4.3±3.0 and 4.8±3.4 times over follow-up. On successive measurements at a median of 4.8, 7.1, and 8.7 years postpartum, respectively, each lipid and glycemic measure progressively worsened from GDM-/CVD- to GDM+/CVD- to GDM-/CVD+ to GDM+/CVD+ (all p<0.0001). At each point in time, each of the lipid and glycemic measures was significantly worse in GDM+/CVD+ compared to GDM+/CVD- (all p<0.001). Moreover, among women who did not develop CVD, all lipid and glycemic measures were significantly worse in those with previous GDM (all p<0.001 for GDM+/CVD- vs GDM-/CVD-). Mediation analyses revealed that the dominant determinants of CVD risk in women with GDM were A1c (56.0% mediation, 95%CI 47.4-67.8) and fasting glucose (47.4%, 38.8-60.8), followed by HDL (25.2%, 21.3-30.7) and triglycerides (12.1%, 9.7-15.6). Upon exclusion of those who developed diabetes during follow-up, the key determinants were HDL (40.8%), fasting glucose (37.7%), A1c (28.6%), triglycerides (21.0%), and LDL (9.9%). Adverse glycemic and lipid measures mediate the elevated risk of CVD in women with previous GDM, with the impact of lipids particularly evident in those who do not develop diabetes. These findings thus identify potential targets for risk factor monitoring and ultimately early intervention towards the goal of primary prevention of CVD in this at-risk patient population.


High-pressure liquid chromatography of the mycotoxins, rubratoxins A and B, and its application to the analysis of urine and plasma for rubratoxin B.
The rubratoxins are toxic metabolites produced by Penicillium rubrum and P. purpurogenum on food and feedstuffs. Rubratoxin B is hepatotoxic, mutagenic and teratogenic. Rubratoxins A and B were resolved as sharp peaks in the order A-B by reversed-phase high-pressure liquid chromatography on a small-particle (10 micrometer) column in 3 min by an acetonitrile-water-ethyl acetate elution solvent (11:9.9:3), with detection by ultraviolet absorbance at 254 nm. The relationship between peak height and quantity injected was linear over a range of 0.25-5 microgram for rubratoxin A and 0.05-5 microgram for rubratoxin B. Retention time and peak height and peak area were highly reproducible for both toxins. Detection was very sensitive, allowing detection of 3-5 ng rubratoxin B, and 15-20 ng rubratoxin A. Quantitative recovery of rubratoxin B from spiked urine samples was obtained over a range of 5-40 microgram/ml, with maximum recovery from urine samples adjusted to pH 2 before extraction. Good recovery of rubratoxin B was also obtained from spiked plasma samples subjected to treatment with 3 N hydrochloric acid followed by extraction with ethyl acetate.


Synthesis and antiviral evaluation of bis(POM) prodrugs of (E)-[4'-phosphono-but-2'-en-1'-yl]purine nucleosides.
Seventeen hitherto unknown bis(POM) prodrugs of novel (E)-[4'-phosphono-but-2'-en-1'-yl]purine nucleosides were prepared in a straight approach and at good yields. Those compounds were synthesized by the reaction of purine nucleobases directly with the phosphonate synthon 3 bearing POM biolabile groups under Mitsunobu conditions. All obtained compounds were evaluated for their antiviral activities against a large number of DNA and RNA viruses including herpes simplex viruses 1 and 2, varicella zoster virus, Feline herpes virus, human cytomegalovirus, HIV-1 and HIV-2. Among these molecules, some of them exhibit anti-VZV and anti-HIV activity at submicromolar concentrations. This class of compound will be of further interest for lead optimization as anti-infectious agents.


miR-3614-5p downregulation promotes cadmium-induced breast cancer cell proliferation and metastasis by targeting TXNRD1.
Cadmium (Cd), which is considered an endocrine disruptor, has been linked to the onset of breast cancer (BC). Our recent study demonstrated that Cd-induced BC progression has a strong correlation with miR-374c-5p dysregulation. The aim of our work was to investigate other potential miRNAs involved in Cd-induced BC cell proliferation and metastasis. In our study, the miRNA profiles of Cd-treated T-47D cells (10 μM, 72 h) were analyzed by miRNA-seq, and our results confirmed that miR-3614-5p was the top downregulated miRNA. Moreover, miR-3614-5p mimic transfection significantly decreased the proliferative ability, migration and invasive ability of BC cell lines (T-47D and MCF-7). Furthermore, we analyzed the overlapping genes from our RNA-seq data and predicted targets from the mirDIP database, and twelve genes (ALDH1A3, FBN1, GRIA3, NOS1, PLD5, PTGER4, RASGRF2, RELN, RNF150, SLC17A4, TG, and TXNRD1) were identified as potential binding targets of miR-3614-5p in the current model. Nonetheless, only miR-3614-5p inhibition caused an increase in TXNRD1 expression upon Cd exposure in T-47D and MCF-7 cell lines. Importantly, luciferase reporter assays further verified that miR-3614-5p suppressed the expression of TXNRD1 by directly binding to the 3'-untranslated region (UTR), and TXNRD1 inhibition significantly repressed the proliferation and metastasis capacity of BC cells upon Cd exposure. Together, our findings demonstrated that Cd exposure repressed the expression of miR-3614-5p, thus activating TXNRD1 expression, which promoted the abnormal proliferation and metastasis of BC cells.


Determination of urinary 8-epi-prostaglandin F(2alpha) using liquid chromatography-tandem mass spectrometry: increased excretion in diabetics.
Liquid chromatography-tandem mass spectrometry (LC/MS-MS) was applied to the quantitative analysis of urinary 8-epi-prostaglandin F(2alpha) (8-epi-PGF(2alpha)) level. 8-Epi-PGF(2alpha) and its internal standard, [(2)H(4)]-8-epi-PGF(2alpha), were extracted from urine by using a solid phase extraction cartridge and loaded to LC/MS-MS in selected reaction monitoring (SRM) mode. The standard curve showed good linearity in the range of 40 pg to 10 ng (r = 0. 997). The accuracy of the added 8-epi-PGF(2alpha) ranged from 96.8 to 104.9% with a mean +/- SD of 99.5+/-2.5%. The average level +/- SD of urinary 8-epi-PGF(2alpha) in 13 healthy volunteers (five women and eight men, 31+/-7.4 years old) was 429.4+/-149.6 pg/mg creatinine. The level of seven patients with noninsulin dependent diabetes mellitus (two women and five men, 40+/-13.6 years old), 630.9+/-275.6 pg/mg creatinine, was statistically higher than that of healthy volunteers (P<0.05). This finding suggested that diabetics are in a highly oxidative condition. This simple and rapid LC/MS-MS method can be used to elucidate the pathophysiological feature of diabetes or for monitoring the curative effect.


The multienzyme architecture of eukaryotic fatty acid synthases.
Eukaryotic fatty acid synthases (FASs) are huge multifunctional enzymes that carry out all enzymatic steps essential for fatty acid biosynthesis. Recent crystallographic studies provide new insights into the architecture of the two distinct eukaryotic FAS systems, the 2.6 MDa heterododecameric fungal and the 540 kDa dimeric animal FAS. In this review, we compare the fundamentally different organization of these two megasynthases and discuss the structural principles of enzyme integration and substrate shuttling in FAS multienzymes.


Analysis of successive endocytic compartments isolated from Dictyostelium discoideum by magnetic fractionation.
A colloidal iron probe was fed to the amoeba Dictyostelium discoideum and chased for different intervals. Successive segments of the endocytic pathway were then isolated magnetically at high yield and purity. There were approx. 500 endocytic vacuoles per cell; their diameters increased from approx. 0.1-0.2 microns after 3 min of feeding to approx. 2 microns after 15 min of feeding and 60 min of chase. The wave-like progression of ingested probes along the endocytic pathway suggested that the transfer of cargo involved a maturation mechanism rather than the shuttling of cargo between stable compartments. The lifetime of primary pinosomes was calculated to be approx. 1 s. Multivesicular bodies were common in the 3 min fraction and abundant in 15 min lysosomes. alpha- and beta-adaptins of molecular masses of approx. 89 and 83 kDa were richer in the 3 min vesicles than in plasma membranes and later endocytic vacuoles. Acid phosphatase, intrinsic vacuole acidity, the vacuolar proton pump protein and pump activity were present at all endocytic stages but rose between the 3 min and 15 min vacuoles and declined thereafter. Bis(monoacyglycero)phosphate or BMP, a lipid characteristic of lysosomes, followed a similar time course; it contributed up to half of the total lipid in lysosomal vacuoles. We conclude that there is both continuity and differentiation along this endocytic pathway.


Dataset of thermographic images for the detection of buried landmines.
This article presents a dataset of thermographic images of terrain with antipersonnel mines to identify the presence or absence of these artifacts using machine learning and artificial vision techniques. The dataset has 2700 thermographic images acquired at different heights, using a Zenmuse XT infrared camera (7-13 µm), embedded in the DJI Matrice 100 drone. The data acquisition experiment consists of capturing aerial infrared images of a terrain where elements with characteristics similar to antipersonnel mines type legbreaker were buried. The mines were planted in the ground between 0 cm and 10 cm deep and were spread over an area of 10 m x 10 m. The drone used a flight protocol that set the trajectory, the time of the flight, the acquisition height, and the image sampling frequency. This dataset was used in "Detection of "legbreaker" antipersonnel landmines by analysis of aerial thermographic images of the soil" [7].


Mobile primary health care clinics for Indigenous populations in Australia, Canada, New Zealand and the United States: a scoping review protocol.
The objective of this review is to explore and examine the available evidence on mobile primary health care clinics for Indigenous populations in Australia, Canada, New Zealand and the United States. Despite the evidence for the effectiveness of primary health care in improving health outcomes, accessing primary care services is often problematic for Indigenous populations in Australia, Canada, New Zealand and the United States. Improving the accessibility of primary health care services for Indigenous populations is considered essential to alleviating the burden of disease and improving well-being. The review will consider literature that discusses the implementation of a mobile primary health clinic for Indigenous populations. Mobile primary health care clinics targeting Indigenous populations of all ages will be included in this review. Transportable clinics (e.g. van, truck or bus) fitted with health care equipment that deliver health services in a defined geographical area will be included. Only literature published in English from 1 January 2006 will be included. Ovid MEDLINE, CINAHL, Embase, Cochrane Database of Systematic Reviews and SocINDEX will be searched, as well as gray literature sources. The full-text of selected literature will be retrieved and assessed in detail against the inclusion criteria by two independent reviewers. Data will be extracted by two independent reviewers, and a narrative summary will be provided on the objectives, concepts and results of the review question.


Management of aortic arch hypoplasia in neonates and infants.
Surgical management of aortic arch hypoplasia (AAH) with associated intracardiac anomalies is a challenge in newborns. We reviewed the characteristics and outcomes of neonates and infants who underwent pulmonary artery banding concomitant to arch repair and single-stage total repair at our institution. Medical records of 60 patients undergoing aortic arch reconstruction for AAH from 2014 to 2019 were retrospectively reviewed. Twenty-five patients were female (41.6%), and the age of the patients ranged from 4 to 120 days (median, 19.5 days). The patients were divided into two groups: Group 1 (23 patients) underwent pulmonary artery banding concomitant to arch repair, and Group 2 (37 patients) underwent single-stage total repair in addition to arch repair. All arch repair procedures consisted of an extended (to the midportion of the ascending aorta) patch aortoplasty. Postoperative early mortality occurred in 12 patients, eight in Group 1 (34.8%) and four in Group 2 (10.8%). There was an early survival advantage in Group 2 (p = .019). Recoarctation occurred in 13 cases (21.6%), and 11 (18.3%) of them required reintervention (balloon angioplasty: 7, reoperation: 4). On univariate analysis, risk factors associated with death were pulmonary artery banding (hazard ratio [HR], 0.44; confidence interval [CI], 0.09-2; p = .019), prematurity (HR, 4.67; CI, 1.34-16.18; p = <.001), preoperative mechanical ventilation support requirement (HR, 0.048; CI, 0.52-6.39; p = .048), and functional single ventricle (HR, 0.43; CI, 0.1-1.86; p = .006). The mean duration of follow-up was 21.9 ± 15.1 months, and there was no late death in either group. Single-stage repair of AAH with intracardiac pathologies has better results than palliation, according to survival rates and postoperative results. The use of the patch augmentation technique in AAH is valid and associated with an acceptable incidence of recurrent arch obstruction.


Benchmarking Outcomes after Ablative Radiotherapy for Molecularly Characterized Intrahepatic Cholangiocarcinoma.
We have previously shown that ablative radiotherapy (A-RT) with a biologically effective dose (BED10) ≥ 80.5 Gy for patients with unresectable intrahepatic cholangiocarcinoma (ICC) is associated with longer survival. Despite recent large-scale sequencing efforts in ICC, outcomes following RT based on genetic alterations have not been described. We reviewed records of 156 consecutive patients treated with A-RT for unresectable ICC from 2008 to 2020. For 114 patients (73%), next-generation sequencing provided molecular profiles. The overall survival (OS), local control (LC), and distant metastasis-free survival (DMFS) were estimated using the Kaplan-Meier method. Univariate and multivariable Cox analyses were used to determine the associations with the outcomes. The median tumor size was 7.3 (range: 2.2-18.2) cm. The portal vein thrombus (PVT) was present in 10%. The RT median BED10 was 98 Gy (range: 81-144 Gy). The median (95% confidence interval) follow-up was 58 (42-104) months from diagnosis and 39 (33-74) months from RT. The median OS was 32 (29-35) months after diagnosis and 20 (16-24) months after RT. The one-year OS, LC, and intrahepatic DMFS were 73% (65-80%), 81% (73-87%), and 34% (26-42%). The most common mutations were in IDH1 (25%), TP53 (22%), ARID1A (19%), and FGFR2 (13%). Upon multivariable analysis, the factors associated with death included worse performance status, larger tumor, metastatic disease, higher CA 19-9, PVT, satellitosis, and IDH1 and PIK3CA mutations. TP53 mutation was associated with local failure. Further investigation into the prognostic value of individual mutations and combinations thereof is warranted.


Ophthalmic delivery systems based on drug-polymer-polymer ionic ternary interaction: in vitro and in vivo characterization.
Aim of the work was to develop mucoadhesive eyedrops containing tetrahydrozoline hydrochloride (TZ), a decongestant drug, and based on a ternary interaction drug-polymer-polymer. The anionic polymers assessed were the anionic hyaluronic acid (HA) and polyacrylic acid (PAA), the cationic chitosan (HCS) and the polyelectrolyte gelatin (G). Formulations based on the ternary systems TZ/G/HA, TZ/HCS/HA, TZ/G/PAA and TZ/HCS/PAA at the stoichiometry ratios between cationic and anionic polymers and containing a 10 and 20 fold excess of the anionic polymers were prepared. The formulations were characterized for in vitro mucoadhesive and release properties. The ex vivo/in vivo residence properties were assessed for the formulations that combined the better in vitro mucoadhesive and release properties. The physical stability of the formulations selected was determined following steam sterilization and storage at 25 and 40 degrees C. The synergistic effect of G with HA and PAA improves the mucoadhesion of the formulations while the interaction of HCS with HA and PAA is likely to produce higher neutralization of the anionic polymer charge and minor chain flexibility resulting in a limited mucoadhesion improvement. Both G and HCS participate to control drug release. The selected formulations demonstrate to possess consistency (viscosity) sensitive to the ions of the medium, and probably for this reason the ex vivo/in vivo residence properties could not directly correlated to mucoadhesion and to drug release control properties. However, the formulations are able to maintain levels of TZ detectable until 20 min after the instillation in rabbits, while TZ was not detectable since 3 min after instillation of the drug solution. The physical stability, following steam sterilization and storage, the low viscosity combined with good residence time in conjunctival sac make the TZ/G/20HA the more promising formulation.


Zinc concentrations during mice gestation.
Severe maternal zinc deficiency has a devastating effect on pregnancy outcome. Studies of humans and experimental animals show that maternal zinc deficiency can cause infertility, prolonged labor, intrauterine growth retardation, teratogenesis, severe immunological deficiencies, or fetal death. The additional need for zinc during pregnancy can be met by an increase in zinc intake. An increase in zinc supplements, when excessive, can cause a decrease in copper. Therefore, it is important to determine the zinc and copper concentrations in embryonic tissue in experimental models and their relationship with embryo number and viability. BALB/c mice were divided into groups according to zinc oral supplementation and gestational age. Phagocytosis was assessed in peritoneal macrophages from dams. The zinc and copper concentrations were obtained by inductively coupled plasma-optical emission spectrometry. Zn and Cu data concentrations in all the analyzed samples were above the detection limits. No spectral interferences were found in both elements. Zinc concentrations show a tendency to increase in embryos (14 gestational days and 21 gestational days) supplemented with zinc. Copper concentrations showed a noticeable tendency to diminish (36% and 27%, respectively) in the same period. In contrast, in placenta Zn values were increased by 30% and Cu values were decreased by 26%. We suggest a pivotal role of the placenta metabolism with its homeostatic mechanisms, in these findings. An important increment appeared in the +Zn embryo number (40%) relative to control (-Zn) embryos at 21 d gestational age. Embryo mortality was at 6% in +Zn embryos and at 20% in -Zn embryos. We consider these findings, both in the number and in the viability of +Zn embryos, outstanding.


Human plasma protein levels alter the in vitro antifungal activity of caspofungin: An explanation to the effect in critically ill?
Recent studies have shown low caspofungin concentrations in critically ill patients. In some patients, the therapeutic target, area under the total plasma concentration curve in relation to the minimal inhibition concentration (AUCtot /MIC), seems not to be achieved and therapeutic drug monitoring (TDM) has been proposed. Caspofungin is highly protein-bound and the effect of reduced plasma protein levels on pharmacodynamics has not been investigated. Fungal killing activity of caspofungin in vitro was investigated under varying levels of human plasma protein. Time-kill studies were performed with clinically relevant caspofungin concentrations of 1-9 mg/L on four blood isolates of C. glabrata, three susceptible and one strain with reduced susceptibility, in human plasma and plasma diluted to 50% and 25% using Ringer's acetate. Enhanced fungal killing of the three susceptible strains was observed in plasma with lower protein content (p < .001). AUCtot /MIC required for a 1 log10 CFU/ml kill at 24 h in 50% and 25% plasma was reduced with 36 + 12 and 80 + 9%, respectively. The maximum effect was seen at total caspofungin concentrations of 4-9 × MIC. For the strain with reduced susceptibility, growth was significantly decreased at lower protein levels. Reduced human plasma protein levels increase the antifungal activity of caspofungin in vitro, most likely by increasing the free concentration. Low plasma protein levels in critically ill patients with candidemia might explain a better response to caspofungin than expected from generally accepted target attainment and should be taken into consideration when assessing TDM based on total plasma concentrations.


Behavioural evolution in the cabbage butterfly (Pieris rapae).
Australian and U.K. Pieris rapae differ markedly in their oviposition behaviour; U.K. females produce a more aggregated egg distribution, and lay their eggs more quickly, than do Australian females. The adaptive reason for this divergence probably lies in the relative costs of increased flight time (more costly in the U.K.) and increased local crowding (more costly in Australia). There is also a strong relationship between juvenile developmental rate (at constant temperature) and oviposition behaviour, but the form of this relationship differed between the two populations. The adaptive reasons for the link between developmental rate and behaviour is not clear. It may be that this link represents the tip of the iceberg; i.e. that physiological, developmental, and behabioral characters all co-vary in ways and for reasons that we do not yet understand.


Cytogenetic analysis of an adenoid cystic carcinoma of the Bartholin's gland. A rare, semimalignant tumor of the female genitourinary tract.
Cytogenetic analysis has been performed on short-term cultures from a 56-year-old woman suffering from an adenoid cystic carcinoma of Bartholin's gland. Beside a normal female karyotype, the tumor revealed an abnormal cell line with complex chromosome changes involving the chromosomes 1, 4, 6, 11, 22, and 14. The mainly structural and nonbalanced rearrangements led to the loss of the chromosome segments 1p31----qter, 4q22----q28, 6p12----qter, 11p11.2----pter, 14q24----qter, and 22q13----qter. Clonal numerical aberrations were not observed. To our knowledge, such a tumor has to-date not been cytogenetically investigated.


Physical activity during COVID-19 induced lockdown: recommendations.
Measures aiming at containing the Coronavirus disease 2019 (COVID-19) include isolation, social distancing, and quarantine. Quarantine and other lockdown instruments show promise in reducing the number of COVID-19 infections and deaths. It is reasonable to assume that lockdown leads to reduced levels of physical activity in the general population. Potential detrimental health effects of lockdown, such as psychological distress and physical inactivity induced maladaptations must be addressed. The current review summarizes harmful effects of limited physical activity on mental and physical health due to social distancing and quarantine and highlights the effects of simple physical activity regimes counteracting these detrimental effects, with a special emphasis on acute effects.


An organ-based approach to dose calculation in the assessment of dose-dependent biological effects of ionising radiation in Arabidopsis thaliana.
There is a need for a better understanding of biological effects of radiation exposure in non-human biota. Correct description of these effects requires a more detailed model of dosimetry than that available in current risk assessment tools, particularly for plants. In this paper, we propose a simple model for dose calculations in roots and shoots of Arabidopsis thaliana seedlings exposed to radionuclides in a hydroponic exposure setup. This model is used to compare absorbed doses for three radionuclides, (241)Am (α-radiation), (90)Sr (β-radiation) and (133)Ba (γ radiation). Using established dosimetric calculation methods, dose conversion coefficient values were determined for each organ separately based on uptake data from the different plant organs. These calculations were then compared to the DCC values obtained with the ERICA tool under equivalent geometry assumptions. When comparing with our new method, the ERICA tool appears to overestimate internal doses and underestimate external doses in the roots for all three radionuclides, though each to a different extent. These observations might help to refine dose-response relationships. The DCC values for (90)Sr in roots are shown to deviate the most. A dose-effect curve for (90)Sr β-radiation has been established on biomass and photosynthesis endpoints, but no significant dose-dependent effects are observed. This indicates the need for use of endpoints at the molecular and physiological scale.


The OsABF1 transcription factor improves drought tolerance by activating the transcription of COR413-TM1 in rice.
Water deprivation causes substantial losses in crop yields around the world. In this study, we show that when overexpressed in transgenic rice (Oryza sativa), the bZIP transcription factor OsABF1 confers distinctly different drought-tolerance phenotypes when tethered to the transcriptional activator VP16 versus the transcriptional repressor EAR. We performed chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) assays on transgenic rice lines and determined that OsABF1 binds to DNA sequences containing an ACGT core motif. Analysis of the overlap between the RNA-sequencing and chromatin immunoprecipitation-sequencing data identified 242 OsABF1 target genes involved in multiple aspects of the drought response. Overexpression of one of these genes, COR413-TM1, which encodes a putative thylakoid membrane protein, resulted in a drought-tolerance phenotype without obvious side effects. In addition, OsABF1 directly regulates the expression of the protein phosphatase 2C (OsPP48 and OsPP108) and bZIP (OsbZIP23, OsbZIP46, and OsbZIP72) genes, thus forming a complex feedback circuit in the drought/abscisic acid signaling pathway.


Simultaneous development of adenocarcinoma and gastrointestinal stromal tumor (GIST) in the stomach: case report.
Gastrointestinal stromal tumors (GISTs) and adenocarcinoma are distinct neoplasms originating from different cell layers. Approximately 20% of patients with GIST develop other cancers. We report a case of the coexistence of adenocarcinoma and gastrointestinal stromal tumor (GIST). Gastric endoscopy showed the ulcerated tumor with bleeding along the lesser curvature of the proximal stomach and a submucosal nodule that measured about 3 cm in diameter in the lower part of the stomach body. Their pathological examination showed gastric cancer (poorly differentiated diffuse adenocarcinoma) and GIST (low-risk category). Further, immunohistochemical staining for C-kit and CD34 was positive, while that for SMA and S-100 was negative. Although it is not easy to speculate on the coexistence of adenocarcinoma and GIST, pre-and post-operative diagnoses may be essential, and such cancer development is not considered to be unusual.


Involvement of microsatellite instability in lymph node metastasis of endometrial carcinoma.
We evaluated microsatellite instability (MSI) in primary lesions and lymph node metastatic lesions in 66 patients with endometrial carcinoma (FIGO stage IIIC) accompanied by lymph node metastasis. DNA was extracted from paraffin-embedded tissue of both the primary and lymph node metastatic lesions of endometrial carcinoma, and MSI was evaluated using microsatellite markers at five loci. Microsatellite instability was positive in the primary lesion in 27 patients (41%). All patients with MSI-positive primary lesions also showed MSI-positive in lymph node metastatic lesions. Of the other 39 patients with MSI-negative primary lesions, 4 showed MSI-positive in lymph node metastatic lesions. As the result of individual identification by polymerase chain reaction (PCR) using short tandem repeat loci in these 4 patients, PCR profiles of primary and metastatic lesions matched with those of normal controls in all 4 patients. Therefore, it was confirmed that both primary and metastatic lesions developed from the same individual. These results suggest that MSI is also involved in lymph node metastasis in the development and/or progression of endometrial carcinoma in some patients.


Spontaneous and impulsively evoked otoacoustic emissions: indicators of cochlear pathology?
The first author's right ear produces a spontaneous otoacoustic emission (SOAE) at 7529 Hz and 16 dB SPL. An external continuous tone is able to suppress the SOAE. The 3 dB iso-suppression curve is broadly tuned and displaced, relative to the SOAE, toward higher frequencies. An audiogram notch exists at frequencies just below that of the SOAE. We explain the occurrence of both spontaneous and impulsively evoked OAEs in terms of disruption of active feedback mechanisms of the OHCs upon basilar membrane vibration. According to this hypothesis, each segment of the organ of Corti feeds back positively upon its segment of basilar membrane and negatively upon adjacent segments. If a patch of OHC loss exists, adjacent segments of the basilar membrane are released from the negative feedback and respond to an impulsive stimulus with exaggerated oscillations at their resonance frequencies, thus producing OAEs. At particularly sharp transitions between normal and abnormal regions of the organ of Corti SOAEs may be generated.


Redundant miR-3077-5p and miR-705 mediate the shift of mesenchymal stem cell lineage commitment to adipocyte in osteoporosis bone marrow.
During the process of aging, especially for postmenopausal females, the cell lineage commitment of mesenchymal stem cells (MSCs) shift to adipocyte in bone marrow, resulting in osteoporosis. However, the cell-intrinsic mechanism of this cell lineage commitment switch is poorly understood. As the post-transcription regulation by microRNAs (miRNAs) has a critical role in MSCs differentiation and bone homeostasis, we performed comprehensive miRNAs profiling and found miR-705 and miR-3077-5p were significantly enhanced in MSCs from osteoporosis bone marrow. Both miR-705 and miR-3077-5p acted as inhibitors of MSCs osteoblast differentiation and promoters of adipocyte differentiation, by targeting on the 3'untranslated region (3'UTR) of HOXA10 and RUNX2 mRNA separately. Combined inhibition of miR-705 and miR-3077-5p rescued the cell lineage commitment disorder of MSCs through restoring HOXA10 and RUNX2 protein level. Furthermore, we found excessive TNFα and reactive oxygen species caused by estrogen deficiency led to the upregulation of both miRNAs through NF-κB pathway. In conclusion, our findings showed that redundant miR-705 and miR-3077-5p synergistically mediated the shift of MSCs cell lineage commitment to adipocyte in osteoporosis bone marrow, providing new insight into the etiology of osteoporosis at the post-transcriptional level. Moreover, the rescue of MSCs lineage commitment disorder by regulating miRNAs expression suggested a novel potential therapeutic target for osteoporosis as well as stem cell-mediated regenerative medicine.


Brillouin Spectroscopy in Ophthalmology.
Information about corneal biomechanics is crucial for achieving satisfactory outcomes after surgical corneal interventions, e.g., for astigmatic keratotomies, but also to identify corneas that are at risk for postoperative complications such as corneal ectasia. Hitherto, approaches to characterize corneal biomechanics in an in vivo setting have yielded only minor success, demonstrating the unmet medical need for a diagnostic technique to measure ocular biomechanics. This review shall explain the mechanism of Brillouin spectroscopy and summarize the current scientific knowledge for ocular tissue. PubMed research of relevant experimental and clinical publications, as well as reporting of own experience using Brillouin spectroscopy. Brillouin spectroscopy can measure different biomechanical moduli with a high spatial resolution. Currently, available devices are able to detect focal corneal weakening, e.g., in keratoconus, as well as stiffening after corneal cross-linking. Also, the mechanical properties of the crystalline can be measured. Corneal anisotropy and hydration, together with the dependence on the angle of the incident laser beam in Brillouin spectroscopy, are challenges in the precise interpretation of measured data. A clear advantage in the detection of subclinical keratoconus compared to corneal tomography, however, has not been shown yet. Brillouin spectroscopy is a technique to characterize biomechanical properties of ocular tissue in vivo. Published results confirm ex vivo data of ocular biomechanics; however, further improvements in the acquisition and interpretation of measured data are required until this technique can be used in a clinically viable setting.


Virus and endogenous viral element-derived small non-coding RNAs and their roles in insect-virus interaction.
RNA interference pathways mediated by different types of small non-coding RNAs (siRNAs, miRNAs and piRNAs) are conserved biological responses to exotic stresses, including viral infection. Aside from the well-established siRNA pathway, the miRNA pathway and the piRNA pathway process viral sequences, exogenously or endogenously, into miRNAs and piRNAs, respectively. During the host-virus interaction, viral sequences, including both coding and non-coding sequences, can be integrated as endogenous viral elements (EVEs) and thereby become present within the germline of a non-viral organism. In recent years, significant progress has been made in characterizing the biogenesis and function of viruses and EVEs associated with snRNAs. Overall, the siRNA pathway acts as the primarily antiviral defense against a wide range of exogenous viruses; the miRNA pathways associated with viruses or EVEs function in antiviral response and host gene regulation; EVE derived piRNAs with a ping-pong signature have the potential to limit cognate viral infection.


Mechanisms and clinical prospects of Notch inhibitors in the therapy of hematological malignancies.
Activation of Notch signaling has been implicated in pathogenesis of various hematologic tumors including leukemias, lymphomas, and multiple myeloma. Pre-clinical studies have suggested that inhibition of Notch could be an attractive new approach to treatment of hematologic malignancies. This review discusses most recent findings in the field and potential role of Notch signaling as a therapeutic target focusing on the effects of gamma-secretase inhibitors.


Metabolic alterations in Strongyloidiasis stool samples unveil potential biomarkers of infection.
Strongyloidiasis, a parasitosis caused by Strongyloides stercoralis in humans, is a very prevalent infection in tropical or subtropical areas. Gaps on public health strategies corroborates to the high global incidence of strongyloidiasis especially due to challenges involved on its diagnosis. Based on the lack of a gold-standard diagnostic tool, we aimed to present a metabolomic study for the assessment of stool metabolic alterations. Stool samples were collected from 25 patients segregated into positive for strongyloidiasis (n = 10) and negative control (n = 15) and prepared for direct injection high-resolution mass spectrometry analysis. Using metabolomics workflow, 18 metabolites were annotated increased or decreased in strongyloidiasis condition, from which a group of 5 biomarkers comprising caprylic acid, mannitol, glucose, lysophosphatidylinositol and hydroxy-dodecanoic acid demonstrated accuracy over 89% to be explored as potential markers. The observed metabolic alteration in stool samples indicates involvement of microbiota remodeling, parasite constitution, and host response during S. stercoralis infection.


Three-Dimensional S/CeO₂/RGO Composites as Cathode Materials for Lithium⁻Sulfur Batteries.
In this paper, the synthesis of the three-dimensional (3D) composite of spherical reduced graphene oxide (RGO) with uniformly distributed CeO₂ particles is reported. This synthesis is done via a facile and large-scalable spray-drying process, and the CeO₂/RGO materials are hydrothermally compounded with sulfur. The morphology, composition, structure, and electrochemical properties of the 3D S/CeO₂/RGO composite are studied using X-ray diffraction (XRD), scanning electron microscope (SEM), transmission electron microscopy (TEM), thermal gravimetric analysis (TGA), Raman spectra and X-ray photoelectron spectroscopy (XPS), etc. The electrochemical performance of the composites as electrodes for lithium⁻sulfur batteries is evaluated. The S/CeO₂/RGO composites deliver a high initial capacity of 1054 mAh g-1, and retain a reversible capacity of 792 mAh g-1 after 200 cycles at 0.1 C. Profiting from the combined effect of CeO₂ and RGO, the CeO₂/RGO materials effectively inhibit the dissolution of polysulfides, and the coating of spherical RGO improves the structural stability as well as conductivity.


Complete Genome Characterization of Novel Chinese Porcine Deltacoronavirus Strain SD.
A porcine deltacoronavirus (PDCoV) was isolated and identified from feces of diarrheic piglets in Shandong Province of the Chinese mainland, and the complete genome of the Chinese PDCoV strain, SD, was sequenced and analyzed to further characterize PDCoV circulating in China.


A child an hour: burden of injury deaths among children under 5 in Pakistan.
Globally, more than 875 000 children under the age of 18 die due to injury every year. The rate of child injury death is 3.4 times higher in low-income and middle-income countries than in high-income countries. To study injury mortality burden among children under the age of 5 in Pakistan. Demographic and Health Survey in Pakistan was conducted from September 2006 until February 2007. It included 95 000 households, out of which 3232 households had death of a child under the age of 5 from January 2005 onwards. The Child Verbal Autopsy Questionnaire (CVAQ) was administered to these households with a response rate of 96%. For age group 0-5 years, injury was the sixth leading cause of death and was responsible for 2.5% of all deaths (n=73). For age group 1-5 years, injury was found to be the third leading cause of death (11%) after diarrhoea (18%) and pneumonia (17%). The overall under fives mortality rate due to injury was estimated at 39.5 per 100 000 per year in Pakistan. Drowning (22%), road traffic injuries (12%), burns (11%) and falls (10%) were the most common types of injury. The mortality rate was twice as high in rural areas (32 per 100 000; 95% CI 18 to 45), compared to the urban areas (15 per 100 000; 95% CI 0.3 to 29). Injury is the third leading cause of deaths among children 1-5 in Pakistan. The burden is twice as high in rural areas.


Reduction of dynamic protein concentration range of biological extracts for the discovery of low-abundance proteins by means of hexapeptide ligand library.
Deciphering the protein composition of complex extracts or discovering biologically relevant polypeptides is frequently hindered by large dynamic concentration ranges. The presence of high-abundance proteins suppresses the signal of low-abundance ones, and the most rare proteins are frequently below the sensitivity of available analytical methods. This protocol addresses this problem by using highly diversified hexapeptide ligand libraries for capturing proteins. A protein extract is mixed with the library and because the library has equal amounts of each ligand, theoretically the maximum amount of each protein bound is the same. Under overloading conditions this has the effect of diluting those proteins present in excess of the ligand concentration and concentrating those of relatively lower abundance. Unbound components are washed out and captured species are finally desorbed. The entire sample treatment process takes about half a day and yields a protein solution that could be used as such for mass spectrometry investigations.


Salmonella rarely detected in Mississippi coastal waters and sediment.
Standards for the rapid detection of individual pathogens from environmental samples have not been developed, but in their absence, the use of molecular-based detection methods coupled with traditional microbiology techniques allows for rapid and accurate pathogen detection from environmental waters and sediment. The aim of this research was to combine the use of enrichment with PCR for detection of Salmonella in Mississippi coastal waters and sediment and observe if that presence correlated with levels of enterococci and climatological variables. Salmonella were primarily found in samples that underwent nutrient enrichment and were present more frequently in freshwater than marine waters. Salmonella were detected infrequently in marine and freshwater sediments. There was a significant positive correlation between the presence of detectable Salmonella and the average enterococcal count. An inverse relationship, however, was observed between the frequency of detection and the levels of salinity, turbidity and sunlight exposure. Results from this study indicated the presence of Salmonella in Mississippi coastal waters, and sediments are very low with significant differences between freshwater and marine environments. Using pathogenic and novel nonpathogenic molecular markers, Salmonella do not appear to be a significant pathogenic genus along the Mississippi Coast.


Induction of tumor antigen-specific cytotoxic T cell responses in naïve mice by latex microspheres-based artificial antigen-presenting cell constructs.
Latex microspheres-based artificial antigen-presenting cell constructs (aAPCs) are proved to be valuable tools to expand T cells ex vivo for adoptive cell therapy, but little is known about their potential for active immunization. In this report, HLA-A2/peptide tetramers were generated and co-coated with anti-mouse CD28 monoclonal antibody onto surface of cell-sized latex microspheres followed by immunization of naïve HLA-A2/K(b) transgenic mice. Five- to six-fold expansion of tumor antigen-specific CTLs was observed in the spleen after three rounds of immunization. The consequent splenocytes can efficiently recognize endogenously expressed tumor antigen on the surface of human target cells and cytolyze the tumor cells in an antigen-specific manner. This report provides initially the experimental evidence that latex microspheres-based aAPCs can effectively prime antigen-specific CTL proliferation and cytolysis in naïve mice. This may contribute to a better insight into the potential of microspheres-based aAPCs for active immunization.


Synchronized Cardioversion Performed During Cold Water Immersion of a Heatstroke Patient.
We report a case of cardioversion that was successfully performed on a patient during cold water immersion. The patient deteriorated into unstable ventricular tachycardia while being treated for heatstroke. We elected to perform synchronized cardioversion without first removing the patient from the immersion body bag. The patient survived and was discharged neurologically intact on hospital day 5. There were no evident deleterious effects to the staff, the patient, or the equipment. To our knowledge, this is the first case report in the literature demonstrating the electrical cardioversion of a patient immersed in water.


Pharmacokinetics and toxicology of sparsomycin in beagle dogs.
Sparsomycin is a cytotoxic drug exhibiting a broad spectrum of in vitro activity against murine tumors and many tumor cell lines. It also appears to be a potent stimulator of the antitumor activity of cisplatin against L1210 leukemia in vivo. However, because of its toxicity, the antitumor activity of sparsomycin on murine tumors in vivo has been disappointing. The purpose of our study was to investigate the pharmacokinetics of this drug as well as the possible mechanisms that produce sparsomycin toxicity. Tests on beagle dogs revealed that about 60% of the drug is eliminated by metabolic clearance, while 40% is eliminated by the kidneys. After a single bolus injection of 0.1 mg/kg sparsomycin without narcosis, sparsomycin was eliminated with a t beta 1/2 of 0.6-0.7 h, the AUC being 0.32-0.38 mg.h.l-1, and the volume of distribution (Vd) 0.26 l/kg. In addition to being subject to glomerular filtration, sparsomycin is probably also actively excreted and actively reabsorbed by the renal tubuli. Sparsomycin itself may inhibit its active tubular excretion, thus resulting in a decrease in the drug's renal clearance and its accumulation in the plasma. Sparsomycin appeared to be toxic primarily in the liver, disturbing its function and the synthesis of plasma proteins. Two out of five dogs developed hemorrhagic diathesis due to hypofibrinogenemia and deficiency of other blood-coagulation factors. Sparsomycin was not toxic to the bone marrow.


HoxA10-like proteins in the reproductive tract of the viviparous lizard Eulamprus tympanum and the oviparous lizard Lampropholis guichenoti.
The gene HoxA10 and its protein product are essential for the formation of the extensions of the plasma membrane called uterodomes or pinopods in mammalian uterine epithelia. In mice, the presence of the HoxA10 protein and uterodomes is needed for uterine receptivity to blastocyst implantation. The viviparous lizard Eulamprus tympanum displays uterodomes whereas the oviparous lizard Lampropholis guichenoti does not. To explore the theory that HoxA10 is involved in the formation of uterodomes we investigated whether HoxA10 immunoreactive proteins were present in both species during their reproductive cycles. Oviduct proteins from vitellogenic, gravid or non-reproductive L. guichenoti (n=19) and E. tympanum (n=28) were separated by electrophoresis and analysed by Western blot and specific antibodies to HoxA10. E. tympanum displayed HoxA10 immunoreactive bands at 59 and 63 kDa in 20 out of the 28 samples. All of the L. guichenoti samples displayed HoxA10 immunoreactive bands, 18 had bands at 59 and 64 kDa and 1 animal had a single band at 59 kDa. There were no significant differences in the level of HoxA10 immunoreactivity between the different stages of reproductive cycle in either species. The different molecular mass of the larger band in L. guichenoti (64 kDa) compared to E. tympanum (63 kDa) indicates that the two lizards express different isoforms of the HoxA10-like proteins and it will be interesting in future studies to determine whether there are differences in the biological activity of the proteins that regulate different physiological functions in the uterus of viviparous and oviparous lizards.